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 <http:@www.caccn.com.au/> 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: <CB unpleasant, CB-2CB pleasant, >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 therapy, particularly
      GP IIb/IIIa receptor inhibition, in protecting patients undergoing percutaneous
      intervention.

PMID- 10198736
TI  - Sudden death in dilated cardiomyopathy.
AB  - The purpose of this review is to examine the potential contribution of arrhythmia
      to the occurrence of sudden death in dilated cardiomyopathy (DCM) and to discuss
      current treatment options. We performed a search of the MEDLINE database from
      1985 to the present and the reference citations of selected articles pertaining
      to the prognostic significance, management, and pathophysiology of arrhythmias in
      DCM. A large proportion of patients with DCM die suddenly, most secondary to
      ventricular arrhythmia and a smaller proportion due to bradyarrhythmia. The
      presence and severity of ventricular ectopy may predict risk for sudden death,
      but the role of electrophysiologic study and signal-averaged electrocardiography
      in further risk stratifying patients remains uncertain. Abnormalities of the
      autonomic nervous system and renin-angiotensin-aldosterone axis appear to promote
      the occurrence of ventricular arrhythmias. Angiotensin-converting enzyme
      inhibitors improve overall mortality in congestive heart failure, and the use of
      direct angiotensin-receptor antagonists is currently being studied. In addition,
      beta-receptor antagonists appear to improve morbidity and may prove to improve
      mortality in heart failure as well. Other interventions still under investigation
      include amiodarone and the implantable cardioverter-defibrillator. The underlying
      pathophysiology of sudden death in DCM involves primarily ventricular
      tachyarrhythmia. Angiotensin-converting enzyme inhibitors remain a mainstay of
      improving overall mortality, while further study on the roles for newer drugs and
      devices is ongoing.

PMID- 10198737
TI  - NC100100, a new echo contrast agent for the assessment of myocardial perfusion-
      safety and comparison with technetium-99m sestamibi single-photon emission
      computed tomography in a randomized multicenter study.
AB  - BACKGROUND AND HYPOTHESIS: Myocardial contrast echocardiography using second
      generation agents has been proposed to study myocardial perfusion. A placebo
      controlled, multicenter trial was conducted to evaluate the safety, optimal dose,
      and imaging mode for NC100100, a novel intravenous second-generation echo
      contrast agent, and to compare this technique with technetium-99m sestamibi
      (MIBI) single-photon emission computed tomography (SPECT). METHODS: In a placebo
      controlled, multicenter trial, 203 patients with myocardial infarction > 5 days
      and < 1 year previously underwent rest SPECT and MCE. Fundamental and harmonic
      imaging modes combined with continuous and electrocardiogram-- (ECG) triggered
      intermittent imaging were used. Six dose groups (0.030, 0.100, and 0.300
      microliter particles/kg body weight for fundamental imaging; and 0.006, 0.030,
      and 0.150 microliter particles/kg body weight for harmonic imaging) were tested.
      A saline group was also included. Safety was followed for 72 h after contrast
      injection. Myocardial perfusion by MCE was compared with myocardial rest
      perfusion imaging using MIBI as a tracer. RESULTS: NC100100 was well tolerated.
      No serious adverse events or deaths occurred. No clinically relevant changes in
      vital signs, laboratory parameters, and ECG recordings were noted. There was no
      significant difference between adverse events in the NC100100 (25.7%) and in the
      placebo group (17.9%, p = 0.3). Intermittent harmonic imaging using the
      intermediate dose was superior to all other modalities, allowing the assessment
      of perfusion in 76% of all segments. Eighty segments (96%) with normal perfusion
      by SPECT imaging also showed myocardial perfusion with MCE. However, a
      substantial percentage of segments (61-80%) with perfusion defects by SPECT
      imaging also showed opacification by MCE. This resulted in an overall agreement
      of 66-81% and a high specificity (80-96%), but in low sensitivity (20-39%) of MCE
      for the detection of perfusion defects. CONCLUSION: NC100100 is safe in patients
      with myocardial infarction. Intermittent harmonic imaging with a dose of 0.03
      microliter particles/kg body weight can be proposed as the best imaging protocol.
      Myocardial contrast echocardiography with NC 100100 provides perfusion
      information in approximately 76% of segments and results in myocardial
      opacification in the vast majority of segments with normal perfusion as assessed
      by SPECT. Although the discrepancies between MCE and SPECT with regard to the
      definition of perfusion defects requires further investigation, MCE with NC
      100100 is a promising technique for the noninvasive assessment of myocardial
      perfusion.

PMID- 10198738
TI  - Assessment of quality of life in patients with chest pain and normal coronary
      arteriogram (syndrome X) using a specific questionnaire.
AB  - BACKGROUND: Prognosis in patients with syndrome X (chest pain and normal coronary
      arteriograms) is good; however, persistent chest pain and functional disability
      are common in these patients. Accurate assessment of quality of life may be
      useful for patient management. AIM: The quality of life status in patients with
      syndrome X was assessed using a specific questionnaire. This questionnaire was
      developed and validated for the assessment of quality of life in patients with
      typical chest pain despite normal coronary arteriograms. METHODS: Ninety
      consecutive patients were invited to complete both the questionnaire (on two
      occasions within 2 weeks) and a standardized angina dairy. Fully completed
      questionnaires were received from 66 (73%) patients (mean age 58 +/- 8 years, 55
      women). RESULTS: Answers were scored according to a grading system where higher
      scores indicate worse quality of life. We observed that total scores increased
      with severity of angina (Canadian Class I, 38 +/- 16, II: 93 +/- 29, III-IV, 119
      +/- 23; p < 0.001) and correlated with both the number and the severity of chest
      pain episodes (r = 0.50-0.66: p < 0.001). In patients who remained clinically
      stable (n = 37) during the 2-week assessment, test-retest analysis showed no
      score differences (87 +/- 30 vs. 81 +/- 30; p = 0.1), while total score increased
      in patients (n = 24) whose symptoms worsened (108 +/- 31 vs. 116 +/- 31; p <
      0.02) and was reduced in those (n = 5) whose symptoms improved (55 +/- 37 vs. 39
      +/- 28; p < 0.04). CONCLUSION: Our study shows that quality of life is
      significantly impaired in patients with syndrome X and that the specific
      questionnaire used for assessment is a reliable and sensitive tool for the
      evaluation of quality of life in patients with chest pain and normal coronary
      arteriograms.

PMID- 10198739
TI  - Antigens of the major histocompatibility system in ischemic heart disease and
      idiopathic dilated cardiomyopathy.
AB  - BACKGROUND: Although dilated cardiomyopathy (DCM) is a disease of unknown and
      probably multifactorial etiology, a change in immune mechanisms is presumably
      significant, with many abnormalities in humoral and cellular responses having
      been reported. The heart thus becomes the target organ for an initial episode of
      myocardial damage that triggers an autoimmune response. HYPOTHESIS: The purpose
      of this study was to analyze the frequency of different human leukocyte antigens
      in patients with a diagnosis of well-advanced DCM and ischemic heart failure,
      comparing them with a control group of presumably healthy subjects. METHODS: The
      group with dilated cardiomyopathy consisted of 50 patients (7 women and 43 men),
      aged from 14 to 64 years. The group with ischemic heart disease included 76
      patients (4 women and 72 men), with ages ranging from 34 to 64. The control
      group, consisting of 1,337 presumably healthy subjects from the Spanish
      Mediterranean area, was recruited based on paternity studies. RESULTS: Compared
      with the control group, we found in DCM a greater incidence of B15 (20 vs. 6%)
      and DQ3 (83 vs. 50%) antigens. In ischemic heart disease we found a lower
      incidence of A1 (3 vs. 22%), B8 (5 vs. 12%), and DQ2 (16 vs. 50%) in comparison
      with the control group. CONCLUSIONS: In the Spanish Mediterranean area, the
      presence of antigens B-15 and DQ3 would be associated with advanced DCM. The
      absence of antigens A1, B8, and DQ2 would be associated with the occurrence of
      severe ischemic heart disease.

PMID- 10198740
TI  - Acquired coronary cameral fistulas: are these collaterals losing their
      destination?
AB  - BACKGROUND: The majority of coronary cameral fistulas (CCFs) are congenital in
      origin. On the other hand, acquired coronary cameral fistulas, having various
      etiopathogenic origins, are increasingly recognized. HYPOTHESIS: The aim of this
      study was to assess the possible involvement of coronary atherosclerosis in the
      pathogenesis of acquired coronary cameral fistulas. METHODS: Between 1993 and
      1996 coronary cameral fistulas were detected in seven adults patients with
      coronary atherosclerosis (n = 4) and following myocardial infarction (n = 3) with
      a mean age of 59.3 years (range 40-77). They were analyzed at our hospital.
      RESULTS: Myocardial infarction (MI) was documented in six patients and was
      localized at the same territory of the fistula-related artery in three of them.
      All patients remained asymptomatic after the detection of the fistula. Five
      patients had associated cardiac disorders. Two patients were treated
      conservatively with medical therapy. Coronary artery bypass grafting (CABG) was
      performed in three patients. One patient died while awaiting CABG. Thirty-four
      adult cases with acquired CCFs were collected from the current literature. The
      right coronary artery was the origin of the fistula in 37% and they terminated
      into the right heart-side in 72% of cases. They remained asymptomatic in 62% of
      cases. CONCLUSIONS: It could be concluded that acquired CCFs may complicate the
      course of severe atherosclerosis or myocardial infarction in certain adult
      patients. The symptomatology and treatment strategy is comparable in the
      congenital and acquired types. The distribution of involvement of the right or
      left coronary arteries is equally divided in both the acquired and congenital
      types. Further studies are needed to investigate the precipitating factors for
      the occurrence of and incidence of acquired CCFs in patients with severe
      atherosclerosis or post-MI subjects.

PMID- 10198741
TI  - Attenuated severity of new acute ischemic events in patients with previous
      coronary heart disease receiving long-acting nitrates.
AB  - BACKGROUND: Platelet aggregation and secondary vasoconstriction are key events in
      the genesis of acute coronary syndromes. HYPOTHESIS: Since nitrates have
      vasodilatory and antiaggregant effects, treatment with long-acting nitrates at
      the time of onset of acute coronary syndromes could be associated with
      attenuation of their severity. METHODS: A consecutive series of 533 patients with
      acute coronary syndrome and past history of coronary artery disease admitted to
      the Cardiology Service of a general hospital was studied. A specific
      questionnaire assessed the use of nitrates and other relevant drugs, as well as
      other clinical variables. The diagnosis of unstable angina or acute myocardial
      infarction (MI) was established according to clinical, electrocardiographic, and
      enzymatic criteria. RESULTS: In the whole cohort, 169 patients had MI and 364 had
      unstable angina. Previous use of long-acting nitrates was significantly more
      common in patients with unstable angina (56%) than in those with MI (37%) (p <
      0.0001). Multivariate analysis identified being a nonsmoker [odds ratio: 95%,
      confidence limits (CL) 0.37, 0.23-0.59], previous unstable angina (CL 0.62, 0.41
      0.92), use of aspirin (CL 0.58, 0.41-0.92), and use of long-acting nitrates (CL
      0.61, 0.40-0.93) as the independent predictors of the development of unstable
      angina rather than MI; of these the combination of nitrates and aspirin was the
      strongest predictor. CONCLUSIONS: Long-acting nitrates as well as aspirin are
      suggested to have a protective or modifying effect on the development of acute
      coronary syndromes, favoring unstable angina rather than acute MI.

PMID- 10198742
TI  - The contracted type of endocardial fibroelastosis.

PMID- 10198743
TI  - Coronary artery-main pulmonary artery fistula.

PMID- 10198744
TI  - Digital assessment of the epicardial electrocardiogram: novel methodology for a
      core laboratory for clinical studies.
AB  - BACKGROUND: The epicardial electrocardiogram (ECG) is a sensitive marker for
      cardiac ischemia and has been used as a measure of ischemia in clinical trials.
      We sought to examine the utility of a central ECG laboratory for determining
      ischemic-type ST-segment shifts from epicardial ECG recordings obtained from
      multiple clinical sites. HYPOTHESIS: We speculated that an operator-assisted
      digital ECG core laboratory is feasible, reliable, and efficient, with the
      ability for rapid and accurate interpretation of the epicardial ECG. METHODS: The
      epicardial ECG was recorded via an angioplasty guidewire placed in a coronary
      artery of a patient undergoing angioplasty. Site investigators visually
      determined the time-to-onset of 0.1 and 0.3 mm ST-segment elevation, and the
      maximal ST-segment elevation during balloon inflation, and then compared the
      measurements with those made at an operator-assisted digital ECG core laboratory.
      RESULTS: Agreement between the two methods occurred in 78% of the time-to-onset
      measurements, but in only 39% of the maximal ST-segment measurements. Overall,
      the visual measurements of the clinical investigators of time-to-onset differed
      from the digital core laboratory by 11.8 +/- 11.6 s for 0.1 mV, and 15.8 +/- 20.6
      s for 0.3 mV. Recorded maximal ST-segment shifts differed by a mean of 0.47 +/-
      0.69 mV. CONCLUSION: The magnitude of inconsistency between the ECG core
      laboratory results using an operator-assisted digital method and the
      interpretations of clinical investigators using manual caliper-type analysis was
      surprisingly large. These results support the need for an ECG core laboratory in
      clinical trials where ECG ST-segment shifts are used as a response variable.

PMID- 10198745
TI  - Transient effusive-constrictive pericarditis due to chemotherapy.
AB  - Commonly used chemotherapeutic agents, specifically cytarabine and daunorubicin,
      can cause effusive-constrictive pericarditis. We describe a case of transient
      effusive-constrictive pericarditis in a patient with acute myelogenous leukemia.
      This is the first case report of a patient with transient effusive-constrictive
      pericarditis due to chemotherapy.

PMID- 10198746
TI  - Survival without surgical repair of acute rupture of the right ventricular free
      wall.
AB  - Rupture of the myocardial free wall is an infrequent complication of acute
      myocardial infarction. Unless it occurs in a space confined by pericardial
      adhesions, only surgical emergency repair of ruptured myocardium can prevent
      death. In this paper we report the case of an 81-year-old woman who was admitted
      to the emergency room with cardiac tamponade, resulting from inferolateral acute
      myocardial infarction and a subsequent rupture of the right ventricular free
      wall, with the formation of pericardial thrombus and effusion. The patient
      refused to undergo any surgical or invasive intervention, and therefore she was
      only treated conservatively. Nevertheless, her condition improved dramatically,
      as her blood pressure increased and echocardiography abnormalities almost
      disappeared. Follow-up echocardiography 7 months post discharge was unremarkable.
      We believe that this rare case emphasizes that in special circumstances, such as
      creation of a thrombus that prevents more blood from extravasating, free-wall
      rupture without surgical repair is compatible with long-term survival.

PMID- 10198747
TI  - Etienne-Louis Fallot: is it his tetralogy?

PMID- 10198748
TI  - Intrapericardial therapeutics and diagnostics (IPTD): potential advantages,
      recent advances, experimental direct therapy of cardiac disease and arrhythmias.

PMID- 10198749
TI  - The molecular genetics of arrhythmias and sudden death.

PMID- 10198750
TI  - Coronary bypass surgery after an acute myocardial infarction: will delaying
      surgery decrease cardiac events?

PMID- 10198751
TI  - Iron, thermoregulation, and metabolic rate.
AB  - Iron plays an important role, not only in oxygen delivery to the tissues, but
      also as a cofactor with several enzymes involved in energy metabolism and
      thermoregulation. As a result, much research has been dedicated to understanding
      the ramifications of iron depletion and iron deficiency anemia on the
      physiological functions of these enzymes. There is evidence to suggest that iron
      depletion and iron deficiency anemia cause physiological changes in the body not
      only during exercise, but also under resting conditions. Both rat and human
      studies have produced results revealing elevated levels of norepinephrine in the
      blood and urine of iron-deficient anemic subjects. These studies also provide
      evidence to suggest that elevation in metabolic rate may ultimately lead to
      slower growth rates and lower body weights in iron-deficient anemic animals and
      humans. The focus of this review is on the effects of iron deficiency on
      metabolic rate and thermoregulation. Prior to this discussion, a brief background
      on iron is presented.

PMID- 10198752
TI  - Molecular aspects of cell wall modifications during fruit ripening.
AB  - Fruit ripening is associated with cell wall modifications. The present review
      focuses on cell wall components and the nature of noncovalent and covalent
      interactions in the primary cell wall. The role of structural protein cross-links
      are evaluated within the context of cell wall-mediated changes in texture during
      fruit ripening. The article discusses molecular approaches in fruit cell wall
      interactions to regulate processes in fruit ripening in order to improve post
      harvest textural characteristics.

PMID- 10198753
TI  - Detection and measurement of microbial lipase activity: a review.

PMID- 10198754
TI  - Effect of beta-glucan from oats and yeast on serum lipids.
AB  - Heart disease is the leading cause of death in the U.S. One way to reduce the
      risk of developing the disease is to lower serum cholesterol levels by making
      dietary changes. In addition to reducing intake of total fat, saturated fat, and
      dietary cholesterol, serum cholesterol can be further reduced by added fiber,
      especially from sources rich in beta-glucan. In this review, two sources of beta
      glucan are described; one source is oats and the other yeast. Their chemical
      structures and physical properties are compared, and their effect on serum lipid
      levels is described. Oat beta-glucans are found in various breakfast cereals and
      snacks. Usually, several servings of these products are required to meet the Food
      and Drug Administration's claim of reducing the risk of heart disease. The yeast
      derived fiber is a more concentrated source of beta-glucan than the oat product.
      It is currently being tested in a wide variety of food products.

PMID- 10198755
TI  - [New trends in chronopharmacology].
AB  - The article discusses the main trends of modern pharmacology associated with the
      use of new experimental models, the choice of adequate objects of study, the
      creation of original drug forms.

PMID- 10198756
TI  - [The reactivity of laboratory mice in pharmacological tests as dependent on their
      zoosocial status].
AB  - The study was conducted on dominant and inferior albino laboratory mice united in
      small groups according to linear hierarchy. Naloxone, amphetamine, and 5
      hydroxytryptophan were used in the pharmacological tests, estimating,
      respectively, the pain response in the hot plate test, motor activity in the
      actometer, and the appearance of the specific stereotyped "head-twitching"
      response. The dominant subjects were less sensitive to amphetamine and 5
      hydroxytryptophan than the inferior of animals, whereas the effect of naloxone
      depended on the level of the zoosocial stress. Therefore, the rank of the animal
      in the group is the factor modulating the behavioral effect of the
      pharmacological agents and should be taken into account in studying the
      individual sensitivity to them.

PMID- 10198757
TI  - [The mechanisms of the neurotropic action of bromantan].
AB  - The main components of bromantan central neurotropic effect is its dopamine
      positive activity: antagonism (5 mg/kg) to the effects of neuroleptics in rats,
      blocking (50 microM) of dopamine synaptosomal capture, and a complicated in
      structure influence on the serotoninergic mediator systems--inhibition of
      neuronal capture of serotonin (50 microM), behavior responses to 5
      hydroxytryptophan (1-20 mg/kg) in mice, decrease in the mediator content in
      intact rat brain when administered in doses lower than 5 mg/kg, and the absence
      of this parameter with the use of higher doses. The central noradrenergic effect
      of the drug is less expressed: blocking of the synaptosomal capture of
      norepinephrine in higher (more than 500 microM) concentrations), and absence of
      an effect, in distinction from sydnocarb, 1-5 mg/kg, on the mediator content in
      intact rat brain. The drug (1-50 mg/kg, intravenously) has no effect on neuro
      muscular transmission in cats and in higher doses (30-600 mg/kg) inhibits to a
      certain degree the central effects of nicotine and arecoline.

PMID- 10198758
TI  - [The participation of the 5-HT1 and 5-HT2 subtypes of the serotonin receptors in
      the formation of the frequency component in the EEG of non-narcotized rats].
AB  - Experiments were conducted on 6 non-narcotized and non-immobilized rats with
      chronically implanted electrodes in the somatosensory area of the brain cortex
      and a cannula in the lateral cerebral ventricle to detect the dose-dependent EEG
      spectra changes after intracerebral injection of quipasin, agonist of 5-HT1--5
      HT2-subtype serotonin receptors. The changes were displayed in a significant
      increase of the rhythms in the subranges 1.5; 4-6; 20-30 Hz and weakening of
      rhythms in 7-16 Hz in comparison to the corresponding parameters in control
      experiments with physiological solution. Preliminary injection of cyproheptadine
      (antagonist of 5-HT1--5-HT2 receptors) weakened significantly the EEG-effects of
      quipasin. Buspirone and ritanserine (agonist and antagonist of 5-HT1 receptors)
      induced EEG changes similar to the effects of cyprohetadine and quipasin,
      respectively. The possible mechanisms of the participation of various subtypes of
      serotonin receptors in the observed EEG effects are discussed.

PMID- 10198759
TI  - [Changes in the local cerebral blood flow during the microdialysis administration
      of vasoactive substances].
AB  - The authors suggest the construction of a cannula for microdialysis combined with
      a light guide of a laser doppler flowmeter. Such a design allows monitoring of
      blood flow intensity in the environment of the microdialyzer. An advantage of
      local administration of vasoactive agents is that they cause no effect on
      systemic arterial pressure. When administered locally, sodium nitroprusside
      increased whereas the inhibitor NO-synthase reduced blood flow intensity. No
      changes were detected in the local blood flow in administration of phenylephrine
      and nitroglycerin through the dialyzer. Tetrodoxin insignificantly reduced the
      blood flow. The existence of a diffusion barrier for some agents as well as the
      long period of time needed for attaining the state of equilibrium after beginning
      perfusion of the solution containing the agent under test is among the
      disadvantages of local administration.

PMID- 10198761
TI  - [The effect of an extract of aspen bark on the development of a chronic
      ulcerative process in animal stomachs].
AB  - The antiulcerogenic activity of aspen bark extract was demonstrated in
      experiments on a model of gastric ulcer in rats. Treatment with a 100 mg/kg dose
      of aspen bark extract led to decrease in the size and more active healing of the
      ulcerous defect in all follow-up periods.

PMID- 10198760
TI  - [The contribution of the mu- and delta-opiate receptors to the realization of the
      vagotropic action of met-enkephalin].
AB  - In cat experiments the effect of methenkephalin on the heart rate, on the
      chronotropic effect of the vagus and its components--tonic and synchronizing was
      compared with the influence of the selective agonists and antagonists mu- and
      delta-opiate receptors. The influence of methenkephalin on the initial heart rate
      and the synchronizing component of the vagal chronotropic effect was found to be
      realized through excitation of the delta-opiate receptors. The modulating effect
      of methenkephalin on the expression of the inhibiting tonic action of the vagus
      was mediated both by the mu- and delta-opiate receptors.

PMID- 10198762
TI  - [The effect of phenazepam on the pancreatic excretory function in thermal
      stress].
AB  - The excretory function of the pancreas was studied on albino rats during thermal
      stress and ACTH (corticotropine) administration. Stress inhibited the enzyme
      synthesizing and enzyme-secreting functions of the gland. The tranquilizer
      phenazepam influencing the GABA-ergic brain systems exerted a protective effect
      on pancreatic exosecretion in stress and its strength depended on the
      administration regimen of the drug. Experiments with corticotropine have shown
      that the antistress effect of phenazepam, to a certain extent is related to its
      action on the level of ACTH production in the hypophysis.

PMID- 10198764
TI  - [The effect of compounds with antioxidant properties on thrombocyte functional
      activity].
AB  - The effect of antioxidant compounds ionol and mexidol and the new phenol
      derivative N9-imidazo-(1,2 alpha)-benzymidazol (PY-185) on the functional
      activity of blood platelets was studied. All the compounds under study
      effectively inhibited blood platelet aggregation both in vitro and in
      administration into rats, a result of which the blood thrombogenic potential
      reduced.

PMID- 10198763
TI  - [The blood-simulating properties of a recombinant colony-stimulating factor and
      glycyram during cytostatic myelosuppression].
AB  - The hemostimulating activity of the drug glycyrram and the recombinant
      granulocytic-macrophagic colony-stimulating factor (CSF) was compared on models
      of myelosuppression induced by injection of an alkylating agent cyclophospane
      (CF) or the antimetabolite 5-fluorouracil (5-FU). It was found that glycerram
      stimulated hematopoiesis more effectively after 5-FU injection but to a lesser
      extent (in relation to CSF) in CF injection.

PMID- 10198765
TI  - [The effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, liposomes with L
      DOPA and "empty" liposomes on the phospholipid composition of the murine liver].
AB  - The effect on the liver phospholipid composition of 1-methyl-4-phenyl -1,2,3,6
      tetrahydropyridine (MPTP) and liposomes containing L-DOPA and those devoid of it
      was studied in experiments on C57B1/6 mice. The content of separate phospholipid
      fractions was expressed in percentage of lipid phosphorus, in nmol lipid
      phosphorus per 1 mg tissue, and in nmol lipid phosphorus per 1 mg protein. It was
      found that the content of phosphatidylinositide and phosphatidylethanolamine
      changed under the effect of MPTP. Injection of liposomes stabilized the level of
      these phospholipids. The concentration of phosphatidylethanolamine was not
      restored in animals injected liposomes devoid of L-DOPA. The main changes
      occurring under the effect of liposomes took place in the sphyngomyelin and
      phosphatidylcholine fractions.

PMID- 10198766
TI  - [The effect of reversible ischemia of the rat liver on antipyrine metabolism and
      the isoenzyme activity of cytochrome P-450].
AB  - The character of changes in the metabolism of antipyrine, etoxy-, methoxy- and
      pentoxyresurphin after total reversible ischemia of the liver was studied in
      rats. In animals highly resistant to hypoxia the metabolism of xenobiotics
      specific to cytochromes P-450 IA1, IA2, and IIB1 was inhibited; in subjects with
      low resistance to hypoxia only P-450 and IA1 activity was suppressed while the
      activity of P-450 IIB1 and IA2 increased 2-3-fold.

PMID- 10198767
TI  - [The effect of ftalazol on the body allowance in rats of B-group vitamins].
AB  - A certain decrease in the content of riboflavin in blood plasma and liver and its
      excretion in the urine were encountered 24-h after administration of phthalazol,
      according to the schedule of acute dysentery treatment, in rats with initial
      moderate deficiency in vitamins B1 and B2. The provision with vitamin B1 did not
      change in this case. The introduction of phthalazol was attended with a
      noticeable decrease in the excretion of pyridoxic acid but did not affect the B6
      content in the liver and blood serum of the animals.

PMID- 10198768
TI  - [The effect of erythromycin on immunity in immunodeficiency].
AB  - The effect of 12.5 and 25 mg/kg doses of erythromycin on the immunity of intact
      mice and in cyclophosphan- and azathioprine-induced immunodeficiency was studied.
      Erythromycin has no effect on the number of antibody-forming cells in the spleen
      of intact and immunocompromised with cyclophosphan animals. It increases their
      number against the background of azathioprine. Immunosuppression may change the
      character of the effect of erythromycin on delayed hypersensitivity. Erythromycin
      stimulates phagocyte activity in intact animals and in immunosuppression.

PMID- 10198769
TI  - [The effect of platinum-containing cytostatic preparations on the immune and
      hematopoietic systems].
AB  - Experiments on male CBA/CA Lac mice [correction of rats] showed that a maximum
      tolerance dose of platidiam suppresses the primary humoral immune response
      stimulated by the thymus-dependent antigen in the late period (30 days), and has
      practically no immunosuppressive effect at the early stages (4 days) after
      injection of the cytostatic drug; it raises the phagocytizing activity of the
      peritoneal macrophages and increases the number of monocytes in the peripheral
      blood.

PMID- 10198770
TI  - [The effect of antitumor chemotherapy on the lipid spectrum of the erythrocyte
      membranes in lung cancer patients].
AB  - The lipid spectrum of erythrocyte membranes was studied by thin-layer and gas
      liquid chromatography in patients with lung cancer in the process of
      antineoplastic cytostatic chemotherapy. The control group of examined subjects
      was formed of healthy volunteers. During a course of antineoplastic
      polychemotherapy according to the CAM scheme (cyclophosphan, adriamycin,
      methotrexate) disorders of the erythrocyte membrane lipid spectrum in patients
      with II-IV stage lung cancer remained or became still more manifest.

PMID- 10198771
TI  - [The effect of contrast agents on latex phagocytosis by mouse neutrophils].
AB  - The authors studied the effect of radiopaque agents (ROA):triombrast, omnipak,
      and ultravist and that of magnetoresonant contrast agents: omniscan and magnevist
      in concentration ranges (10(-4)-10(-2) M) on the phagocytizing activity of mouse
      neutrophils. All contrast agents inhibitors absorption of latex fragments by the
      neutrophils. A strong correlation was revealed between the osmotic activity of
      the radiopaque agents under study and the degree of suppression of neutrophil
      phagocytizing activity.

PMID- 10198772
TI  - [The pharmacological correction of the hepatotoxic action of platidiam].
AB  - A single intravenous infusion of 4.5 mg/kg of the new antineoplastic drug
      platidium induces structural-metabolic changes in the liver of rats (necrosis of
      hepatocytes, decrease of the glycogen and RNA content and accumulation of lipids
      in the cytoplasm of the hepatic cells, and increased activity of aspartate- and
      alaninaminotransferase in blood serum). An additional toxic factor (CCl4) applied
      one month after platidium infusion revealed incompleteness of reparative
      processes in the liver. The hepatoprotector essentiale weakens the injurious
      effect of the cytostatic on the hepatocytes and stimulates regeneration of the
      liver.

PMID- 10198773
TI  - [The histamine receptors of the heart].

PMID- 10198774
TI  - [Changes in lipid metabolism with the use of alcohol deterrent preparations].
AB  - The available experimental and clinical data in the literature on the effect of
      antialcoholic drugs (disulfiram, cyanamide, pyrazol) on the lipid composition of
      tissues (blood serum, liver, brain) are systematized and generalized. Drugs used
      in the treatment of alcoholism were found to cause essential changes in the
      metabolism of lipid fractions. This indicates the necessity for recording the
      detected changes in lipid metabolism in pharmacotherapy of alcoholism.

PMID- 10198775
TI  - [The effect of glucocorticoid preparations on liver metabolism].
AB  - This is a review of experimental and clinical data on the effect of
      glucocorticoid drugs on the metabolism of proteins, carbohydrates, and lipids in
      the liver and its antitoxic function.

PMID- 10198776
TI  - Regulation of bile acid biosynthesis.
AB  - This article provides a review of the pathways through which cholesterol is
      degraded to bile acids. Regulation of key enzymes in the bile acid biosynthestic
      pathways is discussed. The important role of these pathways in the maintenance of
      cholesterol homeostasis and the possible therapeutic implications for the
      treatment of hypercholesterolemia are emphasized.

PMID- 10198777
TI  - Bile acid transport.
AB  - Bile acids undergo a unique enterohepatic circulation, which allows them to be
      efficiently reused with minimal loss. With the cloning of key bile acid
      transporter genes in the liver and intestine, clinicians now have a detailed
      understanding of how the different components in the enterohepatic circulation
      operate. These advances in basic knowledge of this process have directly led to a
      rapid and highly detailed understanding of rare genetic disorders of bile acid
      transport, which usually present as pediatric cholestatic disorders. Mutations in
      specific bile acid or lipid transporters have been identified within specific
      cholestatic disorders, which allows for genetic tests to be established for
      specific diseases and provides a unique opportunity to understand how these genes
      operate together. These same transporters may also prove useful for development
      of novel drug delivery systems, which can either enhance intestinal absorption of
      drugs or be used to target delivery to the liver or biliary system. Knowledge
      gained from these transporters will provide new therapeutic modalities to treat
      cholestatic disorders caused by common diseases.

PMID- 10198778
TI  - The mechanism of biliary lipid secretion and its defects.
AB  - Biliary lipid secretion is an important physiological event; not only for the
      disposal of cholesterol from the body, but also for the protection of cells
      lining the biliary tree against bile salts. Insight into the (patho)physiological
      role of biliary lipid secretion has been recently expanded through the study of a
      generation of mice with a disruption of the Mdr2 gene, who do not secrete lipids
      into bile. Mdr2 P-glycoprotein translocates phospholipids across the
      hepatocanalicular membrane. These animals suffer from progressive liver disease
      caused by the toxic detergent action of bile salts. Very recently, it has become
      clear that an analogous inherited human liver disease exists, which is caused by
      the absence of biliary lipid secretion. Patients with this disease, Progressive
      Familial Intrahepatic Cholestasis (PFIC) type 3, have a mutation in the MDR3
      gene, which is the human homologue of the murine Mdr2 gene.

PMID- 10198779
TI  - Physical and metabolic factors in gallstone pathogenesis.
AB  - Gallstones form when the tenuous balance of solubility of biliary lipids tips in
      favor of precipitation of cholesterol, unconjugated bilirubin, or bacterial
      degradation products of biliary lipids. For cholesterol gallstones, metabolic
      alterations in hepatic cholesterol secretion combine with changes in gallbladder
      motility and intestinal bacterial degradation of bile salts to destabilize
      cholesterol carriers in bile and produce cholesterol crystals. For black pigment
      gallstones, changes in heme metabolism or bilirubin absorption lead to increased
      bilirubin concentrations and precipitation of calcium bilirubinate. In contrast,
      mechanical obstruction of the biliary tract is the major factor leading to
      bacterial degradation and precipitation of biliary lipids in brown pigment
      stones. Further understanding of the physical and metabolic factors of
      cholesterol and black pigment formation is likely to provide interventions to
      interrupt the earliest stages of gallstone formation.

PMID- 10198780
TI  - Gallstone formation. Local factors.
AB  - Bile supersaturation is necessary for cholesterol gallstones to form. Not all
      people with supersaturated bile form gallstones, however, and additional factors
      must be present. The role of pronucleating substances has been extensively
      studied. Of these, proteins, especially mucin, are best understood. Mucin is
      secreted by the gallbladder epithelium and may act as a nidus for crystal
      nucleation. Other proteins that may act as pronucleators include alpha 1-acid
      glycoprotein, alpha 1-antichymotrypsin, phospholipase C, and a small calcium
      binding protein. The role of antinucleating factors is less well understood.
      Certain drugs, including octreotide and ceftriaxone, may also predispose to stone
      formation. Another local factor is gallbladder stasis, a well-known risk factor
      for pigment stone formation. More recent research has focused on the role of
      bacterial infection, which has long been believed to be a factor in pigment
      gallstone formation. Newer data also support a role for infection in cholesterol
      gallstone pathogenesis. Additionally, genetic factors that may predispose a
      patient to cholesterol gallstones have been identified in mice and in humans.

PMID- 10198781
TI  - Laparoscopic biliary surgery.
AB  - Treatment of gallstones by laparoscopic cholecystectomy has become standard
      therapy over the past decade and has received wide patient acceptance. Problems
      are infrequent but those such as biliary injury may be serious and continue to be
      a cause of concern. Biliary injury is more likely when surgery is performed in
      the presence of acute inflammation. Laparoscopic bile duct exploration is
      becoming standardized and the results are good. The role of other laparoscopic
      biliary procedures such as biliary bypass is still uncertain.

PMID- 10198782
TI  - Nonsurgical management of gallstone disease.
AB  - Cholelithiasis is a common disease in the United States associated with
      significant morbidity. Surgical treatment with cholecystectomy has been
      increasing with a significant cost to the health care system. Surgical management
      is not without risk. Cholecystectomy has also been associated with a significant
      morbidity and mortality in elderly patients. Cholecystectomies are often
      performed unnecessarily in gallstone patients for nonspecific symptoms. Many
      patients with nonspecific pain, which may have a psychogenic component, continue
      to experience similar pain after cholecystectomy. There are problems in
      determining the symptom status of patients. Patients who believe surgery will
      relieve symptoms may maximize their symptoms, whereas patients who are reluctant
      to undergo surgery may minimize their symptoms. Although cholecystectomy is the
      mainstay of gallstone treatment, bile acid therapy and, if available, ESWL and
      topical dissolution are nonsurgical treatment alternatives in selected patients.
      In selected cases, in particular in the elderly and in other patients at
      increased risk from surgery, nonsurgical management offers lower morbidity and
      mortality than does operative treatment. The decision for surgical versus
      nonsurgical management should be based on both objective selection criteria and
      patient choice.

PMID- 10198783
TI  - Inborn errors of bile acid biosynthesis and transport. Novel forms of metabolic
      liver disease.
AB  - Defective bile acid biosynthesis, metabolism, and transport can now be delineated
      in a wide variety of disease states. This ability to recognize specific
      aberrations, such as the documented inborn errors in bile acid biosynthesis
      manifesting as neonatal cholestasis, offers new opportunities for therapeutic
      intervention. Future studies should determine the incidence of bile acid
      biosynthetic and transport defects in patients with enigmatic and unexplained
      liver diseases.

PMID- 10198784
TI  - Bile acid abnormalities in cholestatic liver diseases.
AB  - There is ample reason to believe that UDCA is the drug of choice in cholestatic
      liver diseases. It is possible that UDCA has to be administered for prolonged
      periods to see appreciable reversal in liver damage. Nevertheless, the
      amelioration of symptoms and improvement in nutrition of patients are equally
      important. Disabling symptoms such as pruritus are often brought under control,
      and quality of life improves. Clearly the goal for UDCA therapy is to slow the
      rate of disease progression, lessen the mortality risk, and improve the quality
      of life in patients. It is possible that a combination therapy would be more
      beneficial than UDCA alone. Initial results of administering UDCA with colchicine
      have shown no improvement in liver histology; however, administration of UDCA
      together with a strong anti-inflammatory drugs may be helpful to halt immune
      destruction of liver cells.

PMID- 10198785
TI  - Mechanism of hepatoprotective action of bile salts in liver disease.
AB  - Ursodeoxycholic acid (UDCA) improves liver enzymes and in many instances liver
      histology in cholestatic liver diseases such as primary biliary cirrhosis and
      primary sclerosing cholangitis. Besides classic cholestatic diseases, UDCA also
      improves liver biochemistry in alcoholic liver disease and in chronic viral
      hepatitis C. The main target of UDCA treatment, however, is cholestasis, and
      consequently the mechanisms responsible for the beneficial effects in these
      diseases are of interest, and are discussed in detail in this article.

PMID- 10198786
TI  - Role of the enterohepatic circulation of bile salts in lipoprotein metabolism.
AB  - The enterohepatic circulation of bile salts and cholesterol plays a central role
      in maintaining whole body cholesterol homeostasis. Hepatic lipoprotein metabolism
      is reviewed and the role of disturbances in bile salt metabolism in the
      pathogenesis of dyslipidemias is discussed. Further, the manipulation of bile
      salt metabolism to treat dyslipidemia is reviewed.

PMID- 10198787
TI  - Gastrointestinal complications of immunosuppression.
AB  - The gastrointestinal manifestations of drug-induced immunosuppression may result
      from direct drug effects, from infectious complications, or both. Graft-versus
      host disease (GVHD) is a third mechanism whereby immunosuppressive agents are
      linked with gastrointestinal injury. This article reviews individual immuno
      suppressive medications, first concentrating on their reported gastrointestinal
      side effects, then reviewing other gastrointestinal phenomena, which may
      represent side effects of immunosuppressive agents but have not been reported
      yet.

PMID- 10198788
TI  - Evolution of the type-1 (Th1)-type-2 (Th2) cytokine paradigm.
AB  - During the past 12 years, since the discovery of murine Th1 and Th2 clones,
      increasing numbers of cells that make type-1 and type-2 cytokines have been
      recognized, and a growing number of these cytokines have been described. Emphasis
      has shifted from the CD4+ T cell, as the source of Th1-Th2 cytokines, to the
      functional effect of the type-1 and type-2 cytokines, independent of their cell
      of origin. Appreciation of the complex interactions of CMI and humoral immune
      responses continues to evolve. If this new paradigm provides insight into
      infectious disease pathogenesis and prevention, then it should allow development
      of new vaccines and vaccine adjuvants against these diseases.

PMID- 10198789
TI  - Genetic vaccines.
AB  - In a few short years, genetic vaccine technology has moved rapidly from a novel
      concept to an important strategy for the development of human and veterinary
      vaccines, for numerous indications. This article discusses current areas in which
      further refinements in technology will influence a variety of infectious disease
      treatments, including intramuscular and intradermal inoculation, gene gun
      inoculation, the mechanism of antigen presentation, and the use of genetic
      adjuvants.

PMID- 10198790
TI  - Immunoglobulin variable regions as idiotype vaccines.
AB  - This article focuses on the use of immunoglobulin variable regions, including Id,
      anti-Id, anticlonotypes, and Id engineering as putative vaccines and vaccine
      strategies for infectious diseases; and specific discussion of Id systems
      involving antigenic determinants associated with potentially pathogenic
      organisms.

PMID- 10198791
TI  - Maintaining and enhancing vaccine immunogenicity.
AB  - This contribution highlights factors involved with maintaining and enhancing
      antigen delivery or immunogenicity. Areas discussed include the cold chain,
      adjuvants, recombinant vectors for antigen delivery, routes for antigen delivery,
      and edible plant vaccines. It is doubtless that the technological understanding
      that underlies these advances is about to revolutionize vaccinology in the near
      future.

PMID- 10198792
TI  - Herpesvirus vaccines. Development, controversies, and applications.
AB  - Herpesviruses present difficult challenges in vaccine development because of
      their ability to evade immune clearance. Data and recommendations regarding the
      live-attenuated varicella vaccine are discussed. Approaches to developing
      vaccines to prevent herpes simplex virus (HSV), cytomegalovirus (CMV), and
      Epstein-Barr virus (EBV)-associated illnesses also are considered.

PMID- 10198793
TI  - Acellular pertussis vaccines in adults.
AB  - The pathogenesis of pertussis, and the epidemiology and clinical manifestations
      of pertussis after childhood are reviewed as a background for a discussion of
      recent clinical trials of acellular pertussis vaccines in adults, and the
      vaccines' potential for routine use in adolescents and adults.

PMID- 10198794
TI  - HIV vaccines.
AB  - In summary, the development of HIV vaccines has progressed from simple first
      generation env subunit vaccines to second-generation vaccines containing multiple
      subunits. Vaccines with epitopes for CMI and Ab responses have broadened the
      immune response and the potential efficacy of these vaccines. It is hoped that
      newer technologies including the development of adjuvants, new types of vaccines,
      such as naked DNA, and new delivery systems, such as liposomes, will evoke
      stronger immune responses with longer duration. Improved schedules for dosing and
      combinations of HIV vaccines may result in longer lasting immune responses. A
      phase III trial is anticipated to begin within the next 2 years. After a
      temporary lull, the outlook for HIV vaccine development is being met once again
      with strong enthusiasm and encouragement for the future.

PMID- 10198795
TI  - Conjugated polysaccharide vaccines.
AB  - The joining of polysaccharide antigens to various proteins can result in
      increased immunogenicity of vaccines composed of such antigens. This article
      discusses conjugated polysaccharide vaccines for Haemophilus influenzae,
      Streptococcus pneumoniae, and Neisseria meningitis. Increased availability and
      use of such vaccines may result in the ability to give more effective vaccines
      earlier in life, further reducing the incidence of diseases caused by these
      organisms.

PMID- 10198796
TI  - Vaccination as a modality to prevent Lyme disease. A status report.
AB  - Recombinant outer surface protein A (OspA) of Borrelia burgdorferi is a highly
      protective immunogen for prevention of Lyme disease in experimental animals.
      Humoral immunity is sufficient for protection. The principal mechanism of action
      is prevention of transmission of the spirochete from tick to host. A recombinant
      OspA vaccine has been licensed for use in dogs. The recent licensure of an OspA
      vaccine for humans resulted from a critical analysis of recently completed
      efficacy studies.

PMID- 10198797
TI  - Travel vaccines.
AB  - Travel-related infectious diseases are exceedingly common, difficult to diagnose,
      and sometimes preventable. Vaccination is one tool for reducing the risk of
      infectious disease for some travelers. Both healthcare providers and travelers
      need to be aware of the new travel vaccines, and new formulations of older
      vaccines that now are available. This article presents an update on vaccines for
      cholera, Japanese encephalitis, rabies, rotavirus, typhoid, and malaria.

PMID- 10198798
TI  - New vaccines against tuberculosis. The status of current research.
AB  - The increasing realization that the current vaccine for tuberculosis, bacille
      Calmette-Guerin (BCG), is of varying effectiveness, and is less protective in
      adults than in children, has prompted new research for a replacement. New
      research has resulted in innovative approaches, including the use of sub-unit
      vaccines, auxotropic vaccines, DNA vaccines, and recombinant vaccines, among
      others. This article reviews these approaches and test results in animal models,
      and discusses their potential for use in humans.

PMID- 10198799
TI  - Anthrax vaccine. Model of a response to the biologic warfare threat.
AB  - Anthrax vaccine is being administered to all 2.4 million active duty, reserve,
      and National Guard troops, as prophylaxis against biologic warfare. The vaccine's
      effectiveness in this setting may be limited. This article discusses unresolved
      issues of safety, with an emphasis on the need for careful surveillance of
      vaccines used by the military, which has sidestepped the commercial process. Also
      considered are ethical issues related to the development and use of military
      biologics, as the United States Army advances its Joint Vaccine Acquisition
      Program, a plan to produce more than ten vaccines specifically for biologic
      warfare threat, and to administer them to all military servicemembers.

PMID- 10198800
TI  - Arthropod vaccines.
AB  - Antigens located in the midgut of the tick are hidden from the host's immune
      system. Egg production of ticks can be reduced when ticks are fed on animals
      vaccinated with midgut antigens of the tick, and a subunit vaccine formulated
      with the recombinant antigen Bm86 is now available that can reduce the number of
      ticks infesting cattle grazing on pasture. Midgut antigens used in vaccines
      against insects that transmit pathogenic organisms to humans have not been as
      effective in reducing insect fecundity and an alternative approach may be
      necessary. Transmission-blocking vaccines directed at interfering with the vector
      pathogen interaction could result in loss of vector competence and block the
      spread of disease-causing organisms.

PMID- 10198801
TI  - Group A streptococcal vaccines.
AB  - The pathogenesis of group A streptococcal infections, and antigens that
      contribute to protective immune responses are reviewed. Several approaches to
      vaccine development are discussed. Data are provided from preclinical studies of
      multivalent M protein-based vaccines that evoke protective antibodies in
      laboratory animals. Also discussed are future strategies for the development of
      broadly protective vaccines, and their potential impact on the incidence of
      streptococcal infections, and acute rheumatic fever.

PMID- 10198802
TI  - Unconventional vaccine targets. Immunization for pregnancy, peptic ulcer, gastric
      cancer, cocaine abuse, and atherosclerosis.
AB  - Vaccine technology can be applied to targets of intervention that currently have
      not been considered preventable by immunization. Targets include some diseases
      caused by, or related to, infectious agents, and other conditions clearly
      unassociated with disease pathogens. This article considers vaccines for
      pregnancy, peptic ulcer disease, gastric cancer, cocaine abuse and
      atherosclerosis.

PMID- 10198803
TI  - Poliovirus immunizations. What goes around, comes around.
AB  - Although poliovirus vaccination is nto new, the recent changes in ACIP
      recommendations involving polio vaccinations are. Currently, wild type poliovirus
      has been eliminated in the Western hemisphere, but vaccine-associated cases
      (VAPP) still occur. The new recommendations are intended to continue providing
      protection and to eliminate VAPP cases from occurring in vaccinees or close
      contacts.

PMID- 10198804
TI  - Women of a middle generation and parent care.
AB  - This article addresses women who are caring for both parents and children, the so
      called sandwich generation or women-in-the-middle. Gerontological studies on this
      topic reflect controversies on the concept as well as on the size of the
      phenomenon. Our study attempts to demonstrate empirically to what extent middle
      aged women respond to the care demands of both the generation ahead as well as
      the generation behind them. A population-based sample among women aged forty to
      fifty-four in the Netherlands (N = 933) is utilized. The study indicates the
      prevalence of women-in-the-middle and presents analyses of their socio
      demographic characteristics as well as of patterns of parent care. Further, the
      potential for a cross-cultural comparison between the Netherlands and other
      countries is discussed regarding parent care as a normative experience and the
      chances of middle-aged women getting "caught" between care demands from two
      generations.

PMID- 10198805
TI  - Phenomenology and the meaning of aging for young and old adults.
AB  - Qualitative methods were used to examine the similarities and differences in the
      meaning of aging for young and old adults. Nineteen young adults and seventeen
      older adults were asked to describe in detail a specific event or time in their
      lives that suggested to them that they were aging. Their responses were reduced
      to significant statements by two independent coders, until a thematic structure
      became apparent. Younger adults associated aging with major events in their
      lives, and even though these events tended to be positive, aging had a negative
      meaning for them. Young adults tended to associate aging with increased
      responsibility and lost freedom. By contrast, older adults associated aging with
      everyday events or no specific events at all, and they perceived aging
      positively. Both young and old adults mentioned themes of times, the body, and
      others.

PMID- 10198806
TI  - The relationship between perceptions of social support and adherence to dietary
      recommendations among African-American elders with hypertension.
AB  - Social support is generally thought to facilitate adherence to recommended
      treatment regimens. Despite a well-documented tradition of social support among
      African Americans, much of the existing research indicates a very limited level
      of adherence, especially to dietary modification. To account for this seeming
      contradiction, forty-one rural-dwelling African Americans with hypertension age
      65+ participated in a series of structured and semi-structured interviews.
      Results indicate that 1) informants perceived themselves to be well-supported by
      family and friends; 2) most informants have achieved a moderate to high level of
      dietary adherence; and 3) no statistically significant relationship existed
      between perceived social support and dietary adherence. The discussion focuses on
      three reasons for this lack of association, including: 1) modest sample size; 2)
      informants' identification of helpful others who defied standard evaluations of
      support; and 3) incremental and gradual dietary changes that required little need
      for social support.

PMID- 10198807
TI  - Social cognitive predictors of nutritional risk in rural elderly adults.
AB  - According to Social Cognitive Theory (Bandura, 1997), nutritional risk would be
      predicted by perceptions of nutrition efficacy, which in turn would be predicted
      from four sources: modeling, verbal support, physiological conditions, and
      nutrition habits. In telephone interviews with 154 rural elderly adults (44 men,
      110 women; mean age = 74.4 years), nutritional risk was measured with Nutritional
      Risk Index (NRI), Nutritional Screening Initiative (NSI), and seven-high-risk
      nutrients consumed less than 50 percent of RDA (Diet Plus Analysis). Nutrition
      efficacy was measured with a new twenty-five-item scale of Perceived Nutrition
      Barriers (PNB). Sources of nutrition-efficacy included: mealtime modeling--shared
      meals, household size; verbal support--people talk to each day, hours talked,
      number of confidants; physiological conditions that may affect nutrition--age,
      body mass, medications, disability, negative affect, and nutrition habits--daily
      food variety, use of meal services. Path analysis was performed with each measure
      of nutritional risk (NRI, NSI, 7-high-risk-nutrients) as a criterion variable,
      nutrition-efficacy (PNB) as a possible mediating variable, and sources of
      nutrition-efficacy as predictor variables. Social Cognitive variables accounted
      for 58 percent of variance in NRI, 49 percent of variance in NSI, and 29 percent
      of variance in seven-high-risk-nutrients. Nutritional risk was directly predicted
      by large households, few shared meals, few confidants, high body mass, many
      medications, and few daily foods; it was indirectly predicted (via PNB) by high
      levels of negative affect. Perceived Nutrition Barriers (PNB) most often
      mentioned were food cost, eating alone, food tastelessness, transportation to the
      store, and chewing difficulty.

PMID- 10198808
TI  - Basal forebrain cholinergic dysfunction-experimental approaches and the diseased
      brain.

PMID- 10198809
TI  - The behavioral functions of the cholinergic basal forebrain: lessons from 192 IgG
      saporin.
AB  - Until recently our understanding of the functional neuroanatomy of the
      cholinergic basal forebrain (CBF) has been hindered by the lack of a lesioning
      technique that is truly selective. The development of the immunotoxin 192 IgG
      saporin (192-sap) has greatly improved our ability to create specific lesions of
      the CBF. Rats with such lesions have been studied in a wide variety of behavioral
      paradigms of learning, memory, and attention. Complete or near-complete
      destruction of the CBF results in deficits in a variety of behavior paradigms
      including passive avoidance, spatial tasks (water and radial mazes), delayed
      matching to position/sample, and attentional tasks. However, interpretation of
      many experiments is hampered by incomplete lesions and/or concomitant damage to
      cerebellar Purkinje neurons. Future studies will need to address these issues.
      Recent development of a similar immunotoxin that is effective in primates should
      permit more sophisticated behavioral analysis of CBF function. Additionally,
      immunotoxins selective for other types of neurons, such as the noradrenergic
      selective anti-DBH-saporin, will permit analysis of the behavioral functions of
      other diffusely projecting systems and how these other systems may interact with
      the CBF.

PMID- 10198810
TI  - The effects of neonatal basal forebrain lesions on cognition: towards
      understanding the developmental role of the cholinergic basal forebrain.
AB  - Abnormal development of the cholinergic basal forebrain has been implicated in
      numerous developmental disabilities such as Rett Syndrome and Down Syndrome. This
      review summarizes recent data using two rodent animal models that involve
      interrupting cholinergic basal forebrain projections on postnatal day 1 and
      postnatal day 7 when basal forebrain fibers are beginning to innervate their
      neocortical and hippocampal targets, respectively. In one model, electrolytic
      lesions in mice aimed at the basal forebrain on postnatal day 1 transiently
      reduce cholinergic markers in neocortex which induce permanent alterations in
      neocortical anatomy that correlate with impairments on cognitive tasks.
      Furthermore, the lesion effects are sex dependent. In another model, 192 IgG
      saporin lesions in rats on postnatal day 7 permanently reduce cholinergic markers
      in neocortex and hippocampus, and result in mild impairments in spatial
      processing, acquisition and exploratory activities. These data suggest that
      during the first postnatal week of development the cholinergic basal forebrain
      system is critical for normal neocortical differentiation and, possibly
      synaptogenesis in neural circuits that will be important for spatial memory and
      acquisition of spatial data. During the second postnatal week of development, the
      cholinergic basal forebrain system appears to take on a role largely similar to
      its adult role in selective attention and processing of new information. These
      studies also suggest strongly that interrupting cholinergic basal forebrain
      innervation of neocortex and hippocampus leads to anatomical and neurochemical
      abnormalities that may serve as neural substrates for some of the cognitive
      deficits seen in disorders such as Rett Syndrome and Down Syndrome.

PMID- 10198811
TI  - Immunolesion of the cholinergic basal forebrain: effects on functional properties
      of hippocampal and septal neurons.
AB  - Deficits in cholinergic function have been documented in a variety of brain
      disorders including Alzheimer's Disease and, to a lesser extent, in normal
      ageing. In the present article, we have reviewed our recent findings on the
      effects of the loss of basal forebrain cholinergic neurons on the functional
      properties of the septohippocampal pathway. In vivo and ex vivo investigations
      were performed in rats following basal forebrain cholinergic lesion with the
      specific immunotoxin 192 IgG-saporin. Our results suggest a significant
      contribution of cholinergic neurons in the rhythmically bursting activity
      recorded within the medial septum. In addition, they give evidence that
      acetylcholine may tonically decrease the glutamatergic synaptic responses in the
      hippocampus whereas the GABAergic mediated inhibitory potentials are not
      affected. The possible contribution of these cholinergic mechanisms in the age
      related functional alterations of the septohippocampal activity is discussed.

PMID- 10198812
TI  - Effects of cholinergic depletion on evoked activity in the cortex of young and
      aged rats.
AB  - Degeneration of cholinergic neurons in the basal forebrain is a neural marker of
      Alzheimer's disease and is associated with perceptual and cognitive deficits. An
      idea that has attracted scientific scutiny is that aging makes the brain more
      susceptible to neurodegenerative diseases such as Alzheimer's. The purpose of
      this study was to compare the effects of the loss of cholinergic input from
      nucleus basalis of Meynert on evoked activity in the posteromedial barrel
      subfield of the somatosensory cortex in young (2-2.5 months) and aged (28-30
      months) male Fisher hybrid rats. The mean firing rate and receptive fields of
      single neurons in the posteromedial barrel subfield of the somatosensory cortex
      were examined after selective lesions of cholinergic neurons in the nucleus
      basalis of Meynert with an immunotoxin. IgG 192-saporin. Functional properties of
      single neurons in young animals were affected much more significantly by
      cholinergic depletion than those in aged animals. In cholinergic-depleted young
      animals, the mean firing rate of evoked activity and receptive field of
      posteromedial barrel subfield neurons were significantly decreased. Cholinergic
      depletion caused a 14% decrease in evoked activity and a 33% increase in
      receptive field size in young animals. The mean firing rate and receptive field
      of single neurons were not affected by cholinergic depletion in aged animals. It
      is concluded that functional properties of cortical sensory neurons in young
      animals are more vulnerable to cholinergic depletion than are those of aged
      animals and that cholinergic depletion does not further impact the properties of
      neurons exposed to the processes of aging.

PMID- 10198813
TI  - Effects of neonatal cholinergic basal forebrain lesions on excitatory amino acid
      receptors in neocortex.
AB  - The role of cholinergic basal forebrain projections in the modulation of cortical
      plasticity and associated functional changes is currently the subject of renewed
      attention. Excitatory amino acid receptors have been identified as mediators of
      cortical topographic efferent and afferent information. In addition some of these
      receptors, notably the NMDA and metabotropic [mGluR] type, participate in
      cortical plasticity. Growing evidence suggests that interactions between
      cholinergic and glutamatergic systems contribute to cognitive cortical functions
      and their anatomical and physiological substrates. Though cholinergic and
      glutamatergic mechanisms have both been shown to be involved in cortical
      morphogenesis, few studies have attempted to study their interactions in
      development. The present study investigates the effect of neonatal lesions to the
      cholinergic basal forebrain on NMDA, AMPA and mGluR receptors in BALB/CByJ mice,
      at two different developmental ages. We demonstrated previously that nBM lesions
      at birth result in transient cholinergic depletion for the first two postnatal
      weeks, substantial morphogenetic alterations in neocortex and cognitive deficits
      by adulthood. We show here that unilateral neonatal lesions result in decreases
      in NMDA and AMPA receptors but increases in mGluRs during the second postnatal
      week (PND 14). At 30 days postnatal, lesion mediated changes were attenuated,
      compared with PND 14, but significant sex differences in control and nBM lesioned
      mice were apparent. These data support the notion that cholinergic/glutamatergic
      interactions are important during early cortical morphogenesis. Moreover, our
      results highlight the fact that cholinergic as well glutamatergic developmental
      mechanisms are sexually dimorphic.

PMID- 10198814
TI  - Differential changes of nicotinic receptors in the rat brain following ibotenic
      acid and 192-IgG saporin lesions of the nucleus basalis magnocellularis.
AB  - The basal forebrain cholinergic neurons are implicated in the pathogenesis of
      neurodegenerative diseases including Alzheimer's disease (AD). The nicotinic
      acetylcholine receptors (nAChRs) have been found to be significantly afflicted in
      AD. To study the underlying mechanisms for dysfunction of the basal forebrain
      cholinergic neurons development of suitable animal models is warranted. In this
      study we investigated the effects of bilateral lesions of the nucleus basalis
      magnocellularis on nAChRs in the rat brain using the cholinergic system selective
      immunotoxin 192-IgG saporin and non-selective excitotoxin ibotenic acid. Changes
      in nAChRs were measured by 3H-cytisine and 3H-epibatidine, two ligands with
      different selectivity for nAChRs subtypes. In the parietal cortex of ibotenic
      acid lesioned rates, the choline acetyltransferase activity (ChAT) was decreased
      by 24% while no changes were detected in the frontal cortex or hippocampus.
      Similarly, a 40% decrease was observed in the number of nAChRs labelled by 3H
      cytisine, but not by 3H-epibatidine, in the parietal cortex, while no changes
      were found in the frontal cortex or hippocampus. Although the 192-IgG saporin
      induced lesions reduced the ChAT activity in the frontal cortex, parietal cortex
      and hippocampus by 77, 50 and 21%, respectively, no changes were observed in the
      number of nAChRs as studied by 3H-cytisine or 3H-epibatidine. The results
      indicate a difference in vulnerability of the cortical nAChR subtypes to
      experimental lesions of the nucleus basalis magnocellularis. The findings in this
      study suggest that a major portion of the nAChRs might be located on non
      cholinergic neurons in the brain.

PMID- 10198815
TI  - Cerebrospinal fluid cholinesterases--markers for loss of cholinergic basal
      forebrain neurons?
AB  - The present study was conducted to test the hypothesis that cholinergic basal
      forebrain neurons are a major source of cerebrospinal fluid (CSF)
      cholinesterases. To address this question enzyme activities of
      acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in both CSF and
      parietal cortex were assayed following selective lesion of basal forebrain
      cholinergic neurons by a single intracerebroventricular application of the
      cholinergic immunotoxin 192IgG-saporin. Cholinergic immunolesions led to a
      dramatic decrease in total AChE activity in parietal cortex, which was due to the
      specific loss of the G4 molecular form while the activity of the G1 form was
      increased as compared to nonlesioned animals. In contrast, the total enzyme
      activity of BChE and its molecular forms were not affected by cholinergic lesion
      in both parietal cortex and CSF. The data suggest, that cholinergic basal
      forebrain neurons are seemingly not a major source of cholinesterases in the CSF,
      and do not provide any evidence for using CSF cholinesterases as a diagnostic
      marker of basal forebrain cholinergic cell loss in humans.

PMID- 10198816
TI  - Glucose metabolism in cholinoceptive cortical rat brain regions after basal
      forebrain cholinergic lesion.
AB  - To address the question whether the changes in cortical glucose metabolism
      observed in patients with Alzheimer's disease are interrelated with, or
      consequences of, basal forebrain cholinergic cell loss, an experimental approach
      was employed to produce cortical cholinergic dysfunction in rat brain by
      administration of the cholinergic immunotoxin 192IgG-saporin. [14C]D-glucose
      utilization in brain homogenates, D-glucose-displaceable [3H]cytochalasin B
      binding to glucose transporters (GLUT). Northern and Western analyses, as well as
      in vivo [14C]2-deoxyglucose autoradiography were used to quantify the regional
      glucose metabolism. Basal forebrain cholinergic lesion resulted in transient
      increases in glucose transporter binding in cortical regions displaying reduced
      acetylcholinesterase activity, already detectable seven days after lesion with
      peak values around 30 days post lesion. Western analysis revealed that the
      changes in total glucose transporter binding are mainly due to changes in the
      GLUT3 subtype only, while the levels of GLUT1 and GLUT3 mRNA (Northern analysis)
      were not affected by cholinergic lesion. Both immunocytochemistry and in situ
      hybridization demonstrated preferential localizations of GLUT1 on brain
      capillaries and GLUT3 on neurons, respectively. A lesion-induced transient
      decrease in [14C]D-glucose utilization seven days post lesion was detected in the
      lesion site, whereas cholinoceptive cortical regions were not affected. In vivo
      [14C]deoxyglucose uptake was transiently increased in cholinoceptive cortical
      regions and in the lesion site being highest between three to seven days after
      lesion. The cholinergic lesion-induced transient up-regulation of cortical
      glucose transporters and deoxyglucose uptake reflects an increased glucose demand
      in regions depleted by acetylcholine suggesting functional links between cortical
      cholinergic activity and glucose metabolism in cholinoceptive target regions.

PMID- 10198817
TI  - Role of NGF in axotomy-induced c-Jun expression in medial septal cholinergic
      neurons.
AB  - The extent of neuronal regeneration after axotomy largely depends on the survival
      capacity of the injured cell. It has been shown for a long time that nerve fiber
      transection results in retrograde changes in the parent neuronal cell body, and
      that these changes may eventually lead to neuronal degeneration. At present,
      little is known about the sequence of events initiated in a nerve cell body by
      the transection of its axonal process. In this report, we will focus on an
      interaction of nerve growth factor (NGF) with the transcription factor c-Jun in
      intact and axotomized septohippocampal projection neurons.

PMID- 10198818
TI  - Morphological, biochemical and behavioural changes induced by neurotoxic and
      inflammatory insults to the nucleus basalis.
AB  - Interest in the basal forebrain cholinergic system has greatly increased since
      neuropathological studies in humans provided evidence that this system is
      severely affected in Alzheimer's disease and other dementing disorders. In
      laboratory animals, disruption of the nucleus basalis cholinergic neurones has
      been produced by several neurotoxic insults in order to obtain a model
      reproducing the behavioural impairment related to the cholinergic deficits. The
      experiments reported in this review demonstrate that excitotoxic amino acids,
      beta-amyloid and lipopolysaccharide, injected directly in the nucleus basalis are
      toxic to the cholinergic neurones in the rat. The excitotoxin lesions of the
      nucleus basalis, although not selective, are a useful tool for producing
      experimental animals with cholinergic hypofunction and for investigating drugs
      able to ameliorate the cholinergic functions. Local injections of amyloid
      peptides in the rat nucleus basalis produced cholinergic hypofunction and some
      behavioural impairment. Finally, an intense glia reaction with a limited
      cholinergic hypofunction and no behavioural impairment was induced by a 4-week
      infusion of lipopolysaccharide in the nucleus basalis. In conclusion, all three
      models, in spite of their limitations, offer useful tools for the study of the
      pathogenetic mechanisms of Alzheimer's disease and for investigating potentially
      useful drugs.

PMID- 10198819
TI  - Perception of species-specific vocalizations in rats: role of the cholinergic
      septo-hippocampal pathway and aging.
AB  - The effect of a chemical lesion of the cholinergic septo-hippocampal pathway
      induced by ethylcholine aziridinium (AF64A) on brain potentials evoked by species
      specific vocalization containing informations of high biological relevance was
      studied in young adult (10 months) and aged (24 months) rats by means of
      neocortical electroencephalographic recordings. In control rats, the perception
      of a rat's vocalization in a life endangering situation (lasting 0.8 s) initiated
      an evoked potential followed by a late positive slow wave (LPSW)-complex and a
      direct current shift with a duration of up to 16 s. Four months after treatment
      with AF64A (2 nmol into each of the lateral ventricles), the mean negative
      component of the initial acoustic evoked potential (peak latency of about 60 ms
      after stimulus onset) was reduced (P = 0.04) both in young adult and aged rats.
      Further changes included a decrease of the late positive wave amplitude in young
      adult rats (P = 0.001) and a shorter duration of the LPSW-complex in aged rats (P
      = 0.03). AF64A induced also changes in specific components revealed by Principle
      Component Analysis, but only in the group of young rats. A decrease in the slow
      wave component (factor 1, 3000-4000 ms after stimulus onset; P = 0.02) was
      observed. Age per se affected the late positive potential shifts as indicated by
      a shorter latency of the late positive wave (P = 0.03). A detailed analysis of
      the major neurotransmitter markers proved an almost exclusive reduction of the
      activity of choline acetyltransferase in the ventral and dorsal hippocampus (up
      to 60%), which was equal in young adult and aged rats. The irreversible loss in
      choline acetyltransferase activity, which was restricted to the hippocampus, was
      associated by a slight reduction in serotonergic function. The present data
      suggest that the complex cognitive and emotional processes initiated by species
      specific vocalization appear to be affected by aging. Furthermore, as a
      consequence of a cholinergic deficit in the hippocampus, the integration
      processes essential for the recognition of the biological meaning of a species
      specific vocalization are considerably disturbed. These findings provide an
      experimental basis for studying disturbances in the perceptual response to
      stimuli of high emotional value in patients with hypocholinergic function as in
      Alzheimer's disease.

PMID- 10198820
TI  - The neural mechanisms underlying cholinergic cell death within the basal
      forebrain.
AB  - The basal forebrain region includes a large group of cholinergic neurons within
      the medial septal area and nucleus basalis magnocellularis (NBM) that project to
      the hippocampus and throughout the neocortex, respectively. This chapter will
      consider the mechanisms that influence why cholinergic cells within the NBM die
      and discuss studies that have manipulated the features of these cells that could
      make them differentially vulnerable to degeneration with aging and Alzheimer's
      Disease (AD). This chapter will focus upon the NBM cholinergic system because
      this regions typically demonstrates a greater degree of cell loss with aging and
      AD.

PMID- 10198821
TI  - Effects of amyloid precursor protein derivatives and oxidative stress on basal
      forebrain cholinergic systems in Alzheimer's disease.
AB  - The dysfunction and degeneration of cholinergic neuronal circuits in the brain is
      a prominent feature of Alzheimer's disease. Increasing data suggest that age
      related oxidative stress contributes to degenerative changes in basal forebrain
      cholinergic systems. Experimental studies have shown that oxidative stress, and
      membrane lipid peroxidation in particular, can disrupt muscarinic cholinergic
      signaling by impairing coupling of receptors to GTP-binding proteins. Altered
      proteolytic processing of the beta-amyloid precursor protein (APP) may contribute
      to impaired cholinergic signaling and neuronal degeneration in at least two ways.
      First, levels of cytotoxic forms of amyloid beta-peptide (A beta) are increased;
      A beta damages and kills neurons by inducing membrane lipid peroxidation
      resulting in impairment of ion-motive ATPases, and glucose and glutamate
      transporters, thereby rendering neurons vulnerable to excitotoxicity. The latter
      actions of A beta may be mediated by 4-hydroxynonenal, an aldehydic product of
      membrane lipid peroxidation that covalently modifies and inactivates the various
      transporter proteins. Subtoxic levels of A beta can also suppress choline
      acetyltransferase levels, and may thereby promote dysfunction of intact
      cholinergic circuits. A second way in which altered APP processing may endanger
      cholinergic neurons is by reducing levels of a secreted form of APP which has
      been shown to modulate neuronal excitability, and to protect neurons against
      excitotoxic, metabolic and oxidative insults. Mutations in presenilin genes,
      which are causally linked to many cases of early-onset inherited Alzheimer's
      disease, may increase vulnerability of cholinergic neurons to apoptosis. The
      underlying mechanism appears to involve perturbed calcium regulation in the
      endoplasmic reticulum, which promotes loss of cellular calcium homeostasis,
      mitochondrial dysfunction and oxyradical production. Knowledge of the cellular
      and molecular underpinnings of dysfunction and degeneration of cholinergic
      circuits is leading to the development of novel preventative and therapeutic
      approaches for Alzheimer's disease and related disorders.

PMID- 10198822
TI  - The effects of apolipoprotein E deficiency on brain cholinergic neurons.
AB  - Previous studies utilizing apolipoprotein E (apoE)-deficient mice revealed
      distinct decreases in the levels of cholinergic synaptic markers of projecting
      basal forebrain cholinergic neurons and no such alterations in other brain
      cholinergic systems. In order to investigate the mechanisms underlying these
      neuron-specific cholinergic effects, primary neuronal cultures from apoE
      deficient and control mice were prepared and characterized. These include basal
      forebrain cultures, which are enriched in projecting cholinergic neurons, and
      cortical cultures, which contain cholinergic interneurons. The levels of
      cholinergic nerve terminals in these cultures were assessed by ligand binding
      measurements of the levels of the vesicular acetylcholine transporter (VAChT).
      This revealed that basal forebrain cultures of apoE-deficient mice contain
      markedly lower VAChT levels (approximately 50%) than do control cultures, but
      that VAChT levels of the corresponding cortical cultures of the apoE-deficient
      and control mice were the same. Time course studies revealed that VAChT levels of
      the basal forebrain cultures increased with culture age, but that the relative
      reduction in VAChT levels of the apoE-deficient cholinergic neurons was unaltered
      and was the same for freshly prepared and for 96 h old cultures. These in vitro
      observations are in accordance with the in vivo findings and suggest that
      projecting basal forebrain cholinergic neurons, but not cholinergic interneurons,
      are markedly dependent on apoE and that similar mechanisms mediate the in vivo
      and in vitro effects of apoE deficiency on cholinergic function.

PMID- 10198823
TI  - Long-term basal forebrain cholinergic-rich grafts derived from trisomy 16 mice do
      not develop beta-amyloid pathology and neurodegeneration but demonstrate
      neuroinflammatory responses.
AB  - Patients with Down syndrome (human trisomy 21) develop neuropathological and
      cholinergic functional defects characteristic of Alzheimer's disease, which has
      been attributed to the location of the Alzheimer beta-amyloid precursor protein
      on chromosome 21. Due to the partial genetic homology between mouse chromosome 16
      and human chromosome 21, murine trisomy 16 was used as a model to study
      functional links between increased expression of the amyloid precursor protein,
      neurodegeneration and neuroinflammatory responses. Basal forebrain cholinergic
      rich tissue derived from trisomy 16 mice at embryonic age of day 16 was
      transplanted into the lateral ventricle of adult normal mice. At 1, 3, 6, 9 and
      12 months after transplantation, the grafts were characterized by
      immunocytochemistry, molecular biological analysis, and stereological methods.
      Grafts survived up to one year and still demonstrated immunoreactivity for
      cholinergic, GABAergic and astroglial cells. Though a 1.5-fold neuronal over
      expression of amyloid precursor protein was detected in brains from trisomy 16
      embryos by Northern analysis, beta-amyloid deposits were found neither in control
      nor trisomic grafts. Detailed stereological analysis of trisomic grafts did not
      reveal any neurodegeneration or morphological changes of cholinergic and
      GABAergic neurons during the course of graft maturation up to one year, as
      compared to grafts derived from euploid tissue. However, both euploid and
      trisomic grafts demonstrated a strong infiltration with T- and B-lymphocytes and
      a significant micro- and astroglial activation (hypertrophic astrocytes) within
      and around the grafts. These observations further suggest that the trisomy 16
      induced neurodegeneration is seemingly due to a lack of neuron supporting factors
      which are provided by either the metabolic interaction of trisomic graft with
      surrounding healthy host tissue or by cells of the immune system infiltrating the
      graft.

PMID- 10198824
TI  - Developmental and aging aspects of the cholinergic innervation of the olfactory
      bulb.
AB  - The olfactory bulb is a limbic paleocortex which receives monosynaptic sensory
      afferents from the olfactory mucosa, and a strong direct cholinergic input from
      the basal forebrain. This review focuses on the rat olfactory bulb as a suitable
      model to study cholinergic involvements in cortical processing, during
      development, adulthood and aging. Anatomical and biochemical data show that
      cholinergic influences upon the bulbar neuronal network are exerted through
      several types of target cells and receptors (muscarinic and nicotinic).
      Functional data indicate that cholinergic afferents to the olfactory bulb are
      involved in local events related to olfactory learning. Neurodegenerative
      disorders such as Alzheimer's disease involve early olfactory deficits and
      typical histopathological lesions in the olfactory bulb. In summary, with its
      exclusively extrinsic cholinergic innervation and direct sensory input, the rat
      olfactory bulb offers the opportunity to study the cellular and molecular
      mechanisms of cholinergic influences on cortical processing, in both normal and
      pathological conditions.

PMID- 10198825
TI  - NGF content in the cerebral cortex of non-demented patients with amyloid-plaques
      and in symptomatic Alzheimer's disease.
AB  - There is increasing evidence that in Alzheimer's disease nerve growth factor
      (NGF) protein and NGF mRNA content in postmortem cortex is not decreased, but may
      even be elevated although the NGF-sensitive cholinergic basal forebrain neurons
      are preferentially affected. However, only little is known about the early
      pathophysiological events leading to Alzheimer's disease. We therefore measured
      the post-mortem NGF concentrations in temporal and frontal cortex of Alzheimer's
      disease patients, non-demented controls without Alzheimer's disease-related
      pathology, as well as non-demented patients with beta A4 plaques who might be
      classified as 'preclinical' cases. In the Alzheimer's disease group we found up
      to 43% increase in NGF concentrations in the frontal and temporal cortex as
      compared to the two other groups. In a subgroup analysis of the non-demented
      patients with plaques, NGF concentrations were lower in the frontal cortex when
      beta A4 plaques were present (46% of the control temporal area) than in patients
      without evidence of frontal plaques (81% of the control temporal area). This NGF
      decrease was paralleled to a similar decrease of choline acetyltransferase
      activity, which is regulated by NGF in the cholinergic basal forebrain. These
      findings support the hypothesis of lower cortical NGF content at the onset of
      plaque formation and of elevated NGF levels in the clinically manifest and
      neuropathologically advanced stage of the disease.

PMID- 10198826
TI  - delta 1-Opioid receptor-mediated control of acetylcholine (ACh) release in human
      neocortex slices.
AB  - In slices of human neocortex, prelabelled with [3H]-choline, the release of [3H]
      acetylcholine reflects the evoked release of endogenous acetylcholine which was
      elicited by the same electrical stimulation paradigm. [3H]-Acetylcholine release
      was depressed by the delta-opioid receptor agonist D-Pen2-D-Pen5-enkephalin. When
      the nerve endings were depolarized by elevating extracellular potassium the
      evoked [3H]-acetylcholine release was similarly depressed by D-Pen2-D-Pen5
      enkephalin in the absence, but not in the presence, of tetrodotoxin which blocks
      action potential propagation. Therefore, the delta-opioid receptor inhibiting
      [3H]-acetylcholine release should not be located to cholinergic nerve terminals,
      but rather to interneurons. The somatostatin2 receptor partial agonist octreotide
      per se did not influence action potential-evoked [3H]-acetylcholine release, but
      prevented the inhibition of release of [3H]-acetylcholine by D-Pen2-D-Pen5
      enkephalin. Similarly, the delta 1-opioid receptor antagonist 7
      benzylidenenaltrexon per se did not influence [3H]-acetylcholine release, but
      prevented of the inhibition of release by D-Pen2-D-Pen5-enkephalin. From the
      present findings we conclude: (1) The evoked release of [3H]-acetylcholine from
      human neocortex slices reflects the release of endogenous acetylcholine. (2) It
      is inhibited in an indirect manner by opioid receptors of the delta 1-subtype,
      which (3) are not localized on cholinergic axon terminals but on soma and
      dendrites of somatostatin-containing interneurons, where they inhibit
      somatostatin release. (4) These interneurons innervate cholinergic nerve endings
      in the human neocortex and appear to facilitate acetylcholine release via
      somatostatin2 receptors.

PMID- 10198828
TI  - [Gastroesophageal reflux. Diagnosis, pathogenesis and stage-adjusted therapy].

PMID- 10198827
TI  - [Monoclonal antibodies in therapy of malignant lymphomas].

PMID- 10198829
TI  - [New developments in therapy of unstable angina pectoris].

PMID- 10198830
TI  - [Liver transplantation].

PMID- 10198831
TI  - [Nephrotic syndrome].

PMID- 10198832
TI  - [Osteoporosis therapy. A pluralistic approach].

PMID- 10198833
TI  - [What is reliable in antibiotic therapy of inflammatory bronchopulmonary
      diseases?].

PMID- 10198834
TI  - [Diagnosis of hemolysis and differential hemolytic anemia diagnosis].

PMID- 10198835
TI  - [34-year-old patient with jaundice and reversible bile duct stenosis].

PMID- 10198836
TI  - [Value of mistletoe therapy in carcinoma patients].

PMID- 10198837
TI  - [Antithrombotic therapy in heart valve diseases pre- and postoperative].

PMID- 10198838
TI  - [Etiologic diagnosis and therapy of pericarditis and pericardial effusion].

PMID- 10198839
TI  - [Diagnosis of chronic pancreatitis].

PMID- 10198840
TI  - [Antithrombotic therapy in pregnancy].

PMID- 10198841
TI  - [Diagnosis of nicotine dependence. Vienna Standard Smoking Questionnaire].

PMID- 10198842
TI  - The riddle of iatrogenic keratectasia.

PMID- 10198843
TI  - Thirty years of intraocular lens implantation: the way it was and the way it is.

PMID- 10198844
TI  - Comparing nuclear disassembly techniques.

PMID- 10198845
TI  - Cataract formation with a phakic IOL.

PMID- 10198846
TI  - Converting from phacoemulsification to ECCE.

PMID- 10198847
TI  - Cartridge cracks with different viscoelastic agents.

PMID- 10198849
TI  - Consultation section. Cataract surgical problem.

PMID- 10198848
TI  - Cartridge cracks with different viscoelastic agents.

PMID- 10198850
TI  - Phaco slice and separate.
AB  - Phaco slice and separate retains the advantages of the chopping techniques of
      Nagahara, Koch, and Fukasaku but replaces chopping or snapping with slicing
      across the center of the phaco-tip-stabilized nucleus using a Nagahara chopper
      and then repositioning the chopper to optimally separate the divided lens halves.
      As the lens is rotated in the capsular bag, small pieces of the nuclear pie are
      sliced off, separated, emulsified, and aspirated. Emulsification and aspiration
      can alternatively be left until most or all the slices have been made. This
      technique works with a broader range of lens densities than other chopping
      techniques and uses no sculpting and very little phaco time. The phaco time
      required for this technique is relatively independent of nuclear density compared
      with a sculpting technique.

PMID- 10198851
TI  - Laser in situ keratomileusis to correct refractive errors after keratoplasty.
AB  - PURPOSE: To assess the safety and effectiveness of excimer laser in situ
      keratomileusis (LASIK) to correct refractive myopia, astigmatism, or both after
      keratoplasty. SETTING: Eye Clinic Day Hospital, Sao Paulo, Brazil. METHODS:
      Twenty-two eyes that had previously had corneal transplantation were studied.
      Laser in situ keratomileusis was performed using the Chiron automated
      microkeratome and the VISX Twenty-Twenty B excimer laser. RESULTS: Mean follow-up
      after LASIK was 10.09 months +/- 3.87 (SD). The spherical equivalent refraction
      dropped from -4.55 +/- 3.66 D before LASIK to -0.67 +/- 1.24 D after surgery. At
      the last examination, 72.7% of patients had a refractive error within +/- 1.00 D
      of emmetropia and 54.5% had uncorrected visual acuity of 20/40 or better. Vector
      analysis of astigmatic correction showed an index of success of 54.0%. Best
      spectacle-corrected visual acuity was unchanged in 8 cases, improved in 9, and
      decreased in 5. Significant endothelial cell loss, keratoplasty wound dehiscence,
      and other serious complications did not develop in any eye. CONCLUSION: The
      correction of refractive error with LASIK in postkeratoplasty patients proved to
      be safe, effective, and predictable. Further studies with longer follow-up are
      needed to determine the method's clinical value.

PMID- 10198852
TI  - Tono-Pen versus Goldmann tonometry after excimer laser photorefractive
      keratectomy.
AB  - PURPOSE: To compare intraocular pressure (IOP) measurements by the Tono-Pen 2
      tonometer and Goldmann applanation tonometer (GAT) in post-photorefractive
      keratectomy (PRK) patients. SETTING: Refractive Surgery Center, Assaf Harofeh
      Medical Center, Zerifin, Israel. METHODS: In 18 patients, IOP was measured by GAT
      and then by Tono-Pen 2 tonometer 2 to 18 months following PRK (mean 6.6 months +/
      5.1 [SD]). Photorefractive keratectomy had been performed in 1 eye of each
      patient; the fellow eyes served as controls. Corneal curvature and thickness were
      evaluated. Ten of the 18 patients were treated with topical steroids. RESULTS: In
      the post-PRK eyes, mean GAT IOP was 1.8 +/- 3.1 mm Hg lower than mean Tono-Pen
      IOP (P = .012); there was no significant IOP difference in the control (fellow)
      eyes. In steroid-treated post-PRK eyes, mean GAT IOP (12.2 mm Hg) was 2.2 +/- 1.3
      mm Hg lower than mean Tono-Pen IOP (14.4 mm Hg) (P = .0007). Mean Tono-Pen IOP in
      steroid-treated post-PRK eyes was 4.3 +/- 3 mm Hg higher than in the fellow eyes
      (P = .0014); mean GAT IOP was only 2.3 +/- 3.5 mm Hg higher (P = .04). In post
      PRK eyes without topical steroid treatment, mean GAT IOP was 2.0 +/- 1.18 mm Hg
      lower than in the fellow eyes (P = .001); there was no significant difference in
      Tono-Pen IOP. There was a negative correlation between the difference in IOP
      values (Tono-Pen minus GAT) and corneal curvature in post-PRK eyes (r = 0.76, P =
      .0108, n = 15). CONCLUSIONS: The Tono-Pen tonometer appeared to be less affected
      than the GAT by the relative flattening, thinning, and anterior stromal decreased
      rigidity of the central cornea that occur following PRK. Post-PRK steroid-induced
      IOP elevation may be masked by the artifactual decrease in GAT IOP.

PMID- 10198853
TI  - Significance of corneal topography in predicting patient complaints after
      photorefractive keratectomy.
AB  - PURPOSE: To evaluate the sensitivity and specificity of postoperative corneal
      topography to predict potential patient complaints after photorefractive
      keratectomy (PRK). SETTING: Doheny Eye Institute, Los Angeles, California, USA.
      METHODS: Postoperative tangential corneal topographic maps, in 0.5 and 1.0
      diopter (D) relative scales, were obtained from patients (n = 34) at least 4
      months after PRK. Topographies of complaining (n = 18) and noncomplaining
      patients (n = 16) were analyzed by 6 masked examiners with 2 different experience
      levels in PRK (experts, n = 2; beginners, n = 4), who assigned the topographies
      to 1 of the 2 groups. RESULTS: Topographies of complainers (sensitivity) and
      noncomplainers (specificity) were correctly classified in 53.2% overall and in
      44.0% and 63.5% (P = .06) in complainers and noncomplainers, respectively.
      Experienced examiners were not significantly more accurate than inexperienced
      examiners (46.3% and 56.6%, respectively; P = .09). Images of 1.0 D scales
      received significantly more correct responses than those of 0.5 D scales (56.4%
      and 50.0% respectively; P = .03). The reproducibility between images for the same
      patient in both scales was significantly better for the experienced examiners
      than the inexperienced examiners (kappa coefficient 0.73 and 0.51, respectively;
      P = .05). CONCLUSIONS: Subjective analysis of postoperative corneal topography
      alone is not sufficient to predict potential patient complaints after PRK.
      Topographic findings should be interpreted only in the context of a complete
      clinical examination.

PMID- 10198854
TI  - Long-term outcome of epikeratophakia.
AB  - PURPOSE: To assess the long-term outcome of epikeratophakia. SETTING: National
      center for pediatric ophthalmology (The Children's Hospital) and ophthalmology
      department in a regional general hospital (Waterford Regional Hospital), Republic
      of Ireland. METHODS: A retrospective clinical review was carried out of 25 eyes
      (20 patients) with epikeratophakia performed over 10 years. Eyes were assigned to
      a children's group (Group 1) or an adult group (Group 2), depending on patient
      age at the time of surgery, and assessed with respect to indication for surgery,
      visual acuity, condition of the implanted lenticule, complications, refraction,
      and corneal topography. Histological analysis was performed on 1 removed
      lenticule. RESULTS: Mean follow-up of all patients was 7.3 years (median 6.8
      years; range 4.0 to 10.0 years). Most eyes (n = 18) were contact lens intolerant.
      Freeze-dried lenticules were implanted in all cases, and all but 1 had stable
      visual acuity from the early postoperative period to last follow-up. In Group 1
      (n = 10), most eyes had a visual acuity of 6/36 or worse preoperatively with an
      improvement of 1 or more lines in 4 eyes. In Group 2 (n = 14), at last follow-up
      most eyes retained good or improved visual acuity by 1 or more lines. Most grafts
      were clear or had insignificant opacities outside the visual axis. The overall
      complication rate was 12%, with the most serious complication being significant
      induced astigmatism requiring removal of 1 epigraft. Mean induced astigmatism was
      2.50 diopters (D) (median 2.00 D; range 1.00 to 6.00 D), which was accurately
      predicted within +/- 1.00 D by corneal topography in 14 of 19 eyes. Histology
      demonstrated infiltration of the implanted lenticule by host keratocytes.
      CONCLUSION: Epikeratophakia, a reversible procedure with a low complication rate,
      resulted in stable visual acuity with good lenticule condition and minimal
      induced regular astigmatism after long-term follow-up.

PMID- 10198855
TI  - Fitting contact lenses after myopic keratomileusis.
AB  - PURPOSE: To evaluate the long-term efficacy and results of contact lens fitting
      following myopic keratomileusis (MKM). SETTING: Department of Ophthalmology,
      Manhattan Eye, Ear, and Throat Hospital, and Swinger Vision Center, New York, New
      York, USA. METHODS: Postoperative fitting of contact lenses was studied as part
      of a prospective evaluation of myopic keratomileusis. In this series, 27 eyes of
      20 patients had residual postoperative refractive errors that were corrected with
      contact lenses. Patients were fit at a mean of 9.4 months after surgery by the
      trial-lens method. Preoperative keratometry readings and refractions, as well as
      postoperative keratometry readings, refractions, and contact lens specifications,
      were recorded and used for fitting. RESULTS: Twenty-six eyes (96%) were fit
      successfully: 24 (89%) with rigid gas-permeable lenses and 2 (7%) with daily-wear
      soft lenses. The mean diameter of the rigid lenses was 10.00 mm (range 9.4 to
      11.0 mm) and the mean base curve, 8.52 mm (range 7.9 to 9.2 mm). The 2 soft
      lenses had base curves of 8.6 and 8.9 mm. The mean lens power was -5.24 diopters
      (D) (range -0.37 to -14.75 D), which was, on average, 4.06 D more myopic than the
      postoperative spectacle refraction. Postoperative keratometry provided a good
      starting point for the trial lens. Lenses were tolerated for up to 16 years. One
      eye, fit with a soft lens, developed significant myopia during the fifth year.
      CONCLUSION: After lamellar refractive surgery, the topography of the cornea is
      significantly altered. Although the postoperative keratometry readings are
      steeper than the actual curvature, they are reasonably reliable for determining
      the base curve of the initial trial lens, validating the use of conventional
      methods of fitting rigid contact lenses in patients who have had MKM.

PMID- 10198856
TI  - Erbium:YAG laser cataract removal: role of fiber-optic delivery system.
AB  - PURPOSE: To review the properties of energy delivery systems and to evaluate the
      efficiency of zirconium-fluoride-based and sapphire fibers delivering erbium:YAG
      (Er:YAG) laser energy in a clinical laser cataract surgery system. SETTING:
      Department of Ophthalmology, Medical College of Virginia Campus of Virginia
      Commonwealth University, and Veterans Affairs Medical Center, Richmond, Virginia,
      USA. METHODS: Thirty-two patients had Er:YAG laser cataract extraction.
      Preoperative visual acuity ranged between finger counting and 20/40 secondary to
      cataract. The endothelial cell count was measured preoperatively and 6 weeks
      after surgery. A zirconium-fluoride-based fiber was used in 23 patients and a
      sapphire fiber in 9 patients. RESULTS: Of the patients examined after 3 months (n
      = 31), 90.3% (n = 28) had a visual acuity of 20/30 or better and 9.7% (n = 3), of
      20/40 or 20/50. Mean endothelial cell loss at 6 weeks was 7.6% +/- 12.8 (SD).
      Posterior capsule rupture with vitreous loss occurred in 3 cases; 1 was
      attributed to laser damage to the capsule. Conversion to ultrasound
      phacoemulsification was required in 13 cases. Suitable fiber materials for Er:YAG
      laser delivery are sapphire, zirconium fluoride, silica, and germanium oxide.
      Toxicity of the latter is under investigation. CONCLUSION: The Er:YAG laser
      emulsified the lens nucleus safely and effectively. These early results include a
      higher than acceptable posterior capsule rupture rate and reflect the surgeon's
      learning curve with a new technology. Effective power delivery can be achieved
      with sapphire- and zirconium-fluoride-based fiber optics through a silica tip.
      The optimal energy delivery system has not been determined.

PMID- 10198857
TI  - Preventing posterior capsule opacification by creating a discontinuous sharp bend
      in the capsule.
AB  - PURPOSE: To clarify which factor--intraocular lens (IOL) design or material-
      contributes most to the inhibition of migrating lens epithelial cells (LECs).
      SETTING: Jinshikai Medical Foundation, Nishi Eye Hospital, Osaka, Japan. METHODS:
      After phacoemulsification, an acrylic IOL with sharp optic edges was implanted in
      1 eye and a poly(methyl methacrylate) (PMMA) IOL with an optic design similar to
      that of the acrylic IOL in the contralateral eye of 4 rabbits. RESULTS: The
      Miyake view and histopathological findings 3 weeks after surgery revealed that
      the lens capsule wrapped tightly around the optic edges, conforming to a
      distinctly sharp rectangular bend there with both IOL types in all rabbits. The
      migrating-LECs were inhibited at the site, and a massive Soemmering's ring
      cataract was formed. CONCLUSIONS: The discontinuous sharp capsule bend created by
      the sharp optic edges in both IOL types appeared to induce contact inhibition of
      the migrating LECs. The preventive effect of an acrylic IOL on posterior capsule
      opacification may be design dependent.

PMID- 10198858
TI  - Adhesion mechanisms of human lens epithelial cells on 4 intraocular lens
      materials.
AB  - PURPOSE: To evaluate lens epithelial cell (LEC) adhesion on different intraocular
      lens (IOL) materials with particular attention to the distribution of proteins
      located in the focal contacts. SETTING: Center of Biotechnological and Clinical
      Research in Ophthalmology, University of Bologna, Italy. METHODS: The IOL
      materials tested were poly(methyl methacrylate) (PMMA), heparin-surface-modified
      PMMA (HSM PMMA), polyHEMA, and silicone. Primary cultures of human LECs were
      established from human anterior capsules obtained during cataract surgery. The
      mean number of cells attached per square millimeter was calculated for each
      material after 24 and 72 hours. Transmission electron microscopy and
      immunocytochemical analysis were performed to detect the proteins actin,
      vinculin, and talin. RESULTS: Mean adhesiveness of human LECs increased over time
      with PMMA and decreased with the other materials. At 72 hours, mean LECs ranged
      from 54.8 cells/mm2 +/- 12.8 (SD) on PMMA to 2.1 +/- 0.7 cells/mm2 on silicone.
      The means for HSM PMMA and polyHEMA fell in between. The cytoskeletal proteins
      were arranged to produce focal contacts in only the LECs cultured on PMMA. The
      LECs cultured on polyHEMA, HSM PMMA, and silicone attached but failed to develop
      focal contacts or stress fibers. CONCLUSION: This study confirms the
      multifactorial pathogenesis of posterior capsule opacification and suggests its
      incidence will be reduced by improving surgical techniques and using IOL surfaces
      that discourage cell adhesion.

PMID- 10198859
TI  - Elastic properties and scanning electron microscopic appearance of manual
      continuous curvilinear capsulorhexis and vitrectorhexis in an animal model of
      pediatric cataract.
AB  - PURPOSE: To compare the tear resistance of anterior capsulotomies using manual
      continuous curvilinear capsulorhexis (CCC) and vitrector-cut capsulotomy
      (vitrectorhexis) techniques in an animal model of the pediatric eye and in 2
      pairs of human infant eyes. SETTING: Department of Ophthalmology, Storm Eye
      Institute, Medical University of South Carolina, Charleston, South Carolina, USA.
      METHODS: Continuous curvilinear capsulorhexis and automated vitrectorhexis
      capsulotomy techniques were performed in 20 pig eyes, 10 with each technique. The
      capsules were then stretched until they ruptured. The forces required for rupture
      after each technique were compared. The forces required for rupture of the pig
      eye lens capsule were also compared with those required for the human infant eye
      lens capsule. Scanning electron microscopy was performed in each group following
      intraocular lens (IOL) insertion. RESULTS: All capsules stretched adequately for
      IOL insertion. The percentage of stretch prior to rupture was higher in the
      capsulorhexis group (mean 157%, range 147% to 169%) than in the vitrectorhexis
      group (mean 135%, range 124% to 147%) (P < .001). The percentage of stretch in
      the human infant eyes was not statistically different from that in the porcine
      eyes (P > .05). CONCLUSIONS: The manual CCC offered greater resistance to capsule
      tearing than the vitrectorhexis and also revealed a more smooth, regular edge. It
      therefore remains the gold standard. However, the vitrectorhexis displayed more
      than adequate resistance to unwanted anterior capsule tears when used for IOL
      insertion through capsulotomy sizes currently used in clinical practice.

PMID- 10198860
TI  - Pseudomonas aeruginosa endophthalmitis caused by contamination of the internal
      fluid pathways of a phacoemulsifier.
AB  - PURPOSE: To report 4 cases of Pseudomonas aeruginosa endophthalmitis caused by
      internal contamination of the internal pathways of a phacoemulsifier. SETTING:
      Ophthalmology Center, Perpignan, France. METHODS: Four clinical cases of
      postoperative endophthalmitis occurred after phacoemulsification. An
      investigation was necessary to prove the cause of the bacteriological
      contamination. RESULTS: Serotyping and ribotyping of the Pseudomonas aeruginosa
      strains obtained from the vitreous samples and from the phacoemulsifier showed
      that all these strains were identical and that the initial site of the
      contamination was the phacoemulsifier. CONCLUSIONS: The profession should be
      cognizant of this cause of endophthalmitis, although its occurrence is rare.
      Cataract surgeons should test samples from the collection bags of their
      phacoemulsifiers to ensure there is no bacteriological contamination.

PMID- 10198861
TI  - Intraocular pressure trends after supranormal pressurization to aid closure of
      sutureless cataract wounds.
AB  - PURPOSE: To measure intraocular pressure (IOP) immediately and 25 minutes after
      small sutureless cataract surgery to estimate the duration of any elevation and
      to evaluate the relationship between supranormal pressurization and an elevated
      IOP 24 hours postoperatively. SETTING: Routine outpatient cataract surgery at a
      tertiary referral center. METHODS: Thirty-six consecutive eyes that had
      uneventful phacoemulsification cataract extraction were studied in a prospective
      fashion. Supranormal pressurization was attempted in all cases. Surgery was
      performed through a 3.5 mm scleral wound. RESULTS: Mean IOP dropped from 38.8 mm
      Hg +/- 11.4 (SD) to 19.8 +/- 5.3 mm Hg 25 minutes after the surgery (P < .0001).
      A subgroup of patients (n = 6) whose IOP was greater than 24 mm Hg 24 hours
      postoperatively had a pressure drop from 36.8 +/- 12.3 mm Hg to 23.2 +/- 6.2 mm
      Hg 25 minutes postoperatively (P = .051). In this subgroup, the mean 24 hour IOP
      then rose to 30.8 +/- 5.2 mm Hg (P = .043). Another subgroup of patients (n = 7)
      whose IOP was greater than 24 mm Hg at 25 minutes had a pressure drop from 46.3
      +/- 8.5 mm Hg to 27.9 +/- 2.4 mm Hg (P = .0014), falling to 21.7 +/- 6.6 mm Hg at
      24 hours (P = .018). CONCLUSION: These findings demonstrate the rapid decline of
      IOP after supranormal pressurization at the conclusion of cataract surgery. In
      addition, supranormal pressurization did not seem to contribute to IOP elevation
      at 24 hours.

PMID- 10198862
TI  - Asymmetric L-shaped corneal no-stitch tunnel incisions for cataract surgery.
AB  - PURPOSE: To assess whether a unilateral asymmetric radial enlargement of a
      corneal tunnel incision for implantation of foldable intraocular lenses yields
      advantages over conventional linear enlargements. SETTING: Department of
      Ophthalmology, University of Brussels, VUB, Belgium. METHODS: Asymmetric corneal
      tunnel incisions with an L-shaped entrance and a concave exit were compared with
      equivalent conventional linear incisions in patients and in postmortem eyes.
      RESULTS: The asymmetric no-stitch L-designs scored consistently better than the
      symmetric linear designs in induced astigmatism, postoperative astigmatic shift,
      complications, and pressure resistance. CONCLUSION: An asymmetric corneal L
      incision is superior to a conventional symmetric linear incision.

PMID- 10198864
TI  - Collagen shield delivery of ofloxacin to the human eye.
AB  - PURPOSE: To determine the ocular penetration of ofloxacin into the anterior
      chamber of the human eye when delivered by a presoaked collagen shield. SETTING:
      University of Colorado School of Medicine, Denver, Colorado. METHODS: This
      prospective randomized clinical study comprised 31 patients having cataract
      surgery. Patients were divided into 2 groups: the first received 3 preoperative
      drops of commercially available topical ofloxacin 0.3% given 10 minutes apart;
      the second had a collagen shield soaked in the same medication applied to the eye
      before surgery. Aqueous humor was extracted immediately before surgery for
      analysis. RESULTS: Mean aqueous concentration was 287 ng/mL +/- 69 (SEM) (range
      40 to 1141 ng/mL) in the drops group and 957 +/- 189 ng/mL (range 214 to 2437
      ng/mL) in the shield group. The difference was statistically significant (P <
      .005). The minimum inhibitory concentration (MIC) for selected ocular pathogens
      is between 500 and 4000 ng/mL. CONCLUSIONS: A collagen shield presoaked in
      commercially available topical ofloxacin and applied before surgery appears safe.
      The MICs for many common ocular pathogens were reached or exceeded. Further study
      is recommended to determine whether this method of infection prophylaxis is an
      acceptable substitute for subconjunctival injections of antibiotics.

PMID- 10198863
TI  - Phacoemulsification in eyes with past pars plana vitrectomy: case-control study.
AB  - PURPOSE: To determine intraoperative and postoperative complications and outcomes
      of phacoemulsification of cataract in eyes that had previous pars plana
      vitrectomy. SETTING: University-based anterior segment disease referral practice.
      METHODS: This was a retrospective case-control study of a surgical series of 52
      consecutive postvitrectomy cataract extractions statistically compared with
      control eyes from the same practice. RESULTS: Cataract extraction followed
      vitrectomy by 2 months to 6 years (mean 19 months). Cataracts with a posterior
      subcapsular component were seen more frequently in postvitrectomy eyes (58%
      versus 25% in control eyes). Cataract extraction after pars plana vitrectomy was
      often more challenging than in control eyes. Challenges included unstable
      posterior capsules, loose zonules, and posterior capsule plaque. Postoperative
      posterior capsule opacification (PCO) was more common in study than in control
      eyes (51% versus 21%; P = .002), especially if expandable gas or silicone oil had
      been used at vitrectomy. Visual acuity improved in 87% of study eyes, with 46%
      achieving a visual acuity of 20/40 or better. In study eyes in which the
      indication for vitrectomy was macular hole or epiretinal membrane, nuclear
      sclerosis was the most common cataract type, no intraoperative complications
      occurred, the PCO rate was low (13%), and visual acuity was better (73% 20/40 or
      better) than in the other study eyes. CONCLUSION: Phacoemulsification after pars
      plana vitrectomy can be performed with a low complication rate and with good
      visual results, although limited by underlying retinal disease. Posterior capsule
      opacification requiring neodymium: YAG capsulotomy was common in this series.

PMID- 10198865
TI  - Effect of cooled intraocular irrigating solution on the blood-aqueous barrier
      after cataract surgery.
AB  - PURPOSE: To evaluate the effect of cooled intraocular irrigating solution during
      phacoemulsification on postoperative blood-aqueous barrier (BAB) disturbance.
      SETTING: Department of Ophthalmology, University of Vienna, Austria. METHODS: In
      a prospective, randomized clinical study, 40 eyes with senile cataract had
      phacoemulsification with irrigating solutions cooled to approximately 10 degrees
      C (n = 20) or at room temperature (n = 20). Surgical procedure and postoperative
      therapy were otherwise identical in both groups. Postoperative BAB disturbance
      was assessed with the laser flare-cell meter on days 1, 3, 7, 14, and 28.
      RESULTS: Anterior chamber flare was significantly lower in the group with cooled
      irrigating solution on postoperative day 1. There was no significant between
      group difference in flare on any other postoperative day. CONCLUSION: Cooled
      intraocular irrigating solution reduced immediate postoperative inflammation
      compared with irrigating solution at room temperature. However, this effect was
      of short duration.

PMID- 10198866
TI  - Assessment of potential macular function using a color saturation discrimination
      test in eyes with cataract.
AB  - PURPOSE: To study the efficacy of a color saturation discrimination test (CSDT)
      in assessing potential macular function in eyes with cataract. SETTING: Yamanashi
      Medical University and Nirasaki City Hospital, Yamanashi, Japan. METHODS: In this
      prospective study of 200 consecutive eyes with cataract, the thresholds of color
      saturation discrimination on 6 hues were measured with the CSDT. The CSDT program
      was run on a personal computer and cathode-ray tube color monitor. The
      preoperative CSDT scores and postoperative visual acuities were compared. In
      addition, preoperative laser interferometry (LI) and postoperative CSDT were
      performed on selected patients and the results compared with their preoperative
      CSDT results. RESULTS: Patients who had a CSDT score of 11 or more had a
      significantly lower postoperative visual acuity (P < .0001). The prevalence of
      neuroretinal abnormality postoperatively increased with the preoperative CSDT
      score. The CSDT score was not correlated with preoperative visual acuity (P =
      1409). Cataract severity had little influence on the CSDT score. The preoperative
      results of the CSDT and Ll were correlated with the postoperative acuity, with
      the correlation coefficient being stronger with the CSDT (r = -0.338 and 0.276
      for CSDT and Ll, respectively). CONCLUSION: The CSDT was effective in evaluating
      neuroretinal pathology and predicting postoperative acuity.

PMID- 10198867
TI  - Functional complaints, visual acuity, spatial contrast sensitivity, and glare
      disability in preoperative and postoperative cataract patients.
AB  - PURPOSE: To quantify cataract patients' functional visual complaints and
      correlate them with their objective glare disability and spatial contrast
      sensitivity (SCS) scores. SETTING: Sir Mortimer B. Davis Jewish General Hospital.
      Montreal, Quebec, Canada. METHODS: Thirty patients scheduled for cataract surgery
      with a visual acuity of 20/70 or better at the time of patient selection and no
      other ocular pathology were evaluated objectively and subjectively for visual
      function preoperatively and within 3 months postoperatively. Objective measures
      of SCS and visual acuity in the presence and absence of glare were obtained with
      the Optec 3000 vision tester. Subjective visual function was evaluated with the
      Activities of Daily Vision Scale (ADVS), a questionnaire that evaluates patients'
      visual function by assessing the degree of difficulty they experience in
      performing tasks involving distance vision, near vision, and glare conditions.
      RESULTS: Preoperatively, patients had decreased visual acuity and SCS in the
      presence of glare. The ADVS scores were correlated with visual performance.
      Postoperatively, there was a statistically significant improvement in all
      dependent measures (i.e., visual acuity and SCS in the presence of glare) as well
      as in the subjective report of visual performance assessed by the ADVS.
      CONCLUSION: Spatial contrast sensitivity, glare disability, and the ADVS
      questionnaire should be considered as adjuncts to visual acuity testing in
      evaluating certain cataract patients.

PMID- 10198868
TI  - Delayed onset keratectasia following laser in situ keratomileusis.
AB  - We present a case of unilateral iatrogenic keratectasia developing 10 months
      after bilateral laser in situ keratomileusis (LASIK) involving enhancement
      surgery using a broad-beam excimer laser (Summit Apex) to treat 6.6 diopters (D)
      of myopia. The ectasia progressed rapidly over the subsequent 12 months. The
      surgeon did not measure preoperative pachymetry, but preoperative topography and
      corneal measurements did not reveal underlying keratoconus or forme fruste
      keratoconus. Corneal transplantation was required for final visual
      rehabilitation. Light microscopy of the button revealed no underlying
      inflammation, which suggests biomechanical corneal weakening as the cause of the
      ectasia. Scanning electron microscopy showed the dramatic thinning seen
      clinically. latrogenic keratectasia appears to be a possible complication of
      LASIK.

PMID- 10198869
TI  - Follow-up of 3 patients with Ridley intraocular lens implantation.
AB  - Three patients in whom Ridley intraocular lenses (IOLs) were successfully
      implanted more than 42 years ago are presented. One case had traumatic cataract
      at age 13. The other 2 had surgery for unilateral cataract of unknown etiology at
      about age 40 and surgery on the second eye approximately 40 years later. A review
      of other reports of late-term results with this IOL is included.

PMID- 10198870
TI  - Lens opacity after neodymium: YAG laser iridectomy for phakic intraocular lens
      implantation.
AB  - We describe a previously unreported complication of a posterior chamber
      intraocular lens (IOL) implanted in a phakic eye. The left eye of a 25-year-old
      patient with high myopia was treated prophylactically with neodymium: YAG (Nd:
      YAG) laser iridotomy prior to phakic IOL implantation. Slitlamp examination of
      the left eye disclosed an opacity of the anterior capsule of the crystalline lens
      under the iridotomy site. This case demonstrates a complication associated with
      Nd:YAG iridotomy prior to implantation of a phakic IOL.

PMID- 10198871
TI  - Suspected ciliary block associated with Viscoat use.
AB  - Ciliary block or malignant glaucoma is thought to be caused by the misdirection
      of aqueous into the vitreous. It is refractory to medical treatment and often
      requires vitreous aspiration. We present a case of ciliary block glaucoma caused
      by sodium chondroitin sulfate-sodium hyaluronate (Viscoat) gaining access to the
      vitreous through an unsuspected, small zonular dialysis. Vitrectomy performed
      through a peripheral iridectomy resolved this severe condition.

PMID- 10198872
TI  - Surgically induced necrotizing scleritis in a patient with ankylosing
      spondylitis.
AB  - We present the case of a 75-year-old man with ankylosing spondylitis who
      developed surgically induced necrotizing scleritis (SINS) more than 3 years after
      uneventful extracapsular cataract extraction and posterior chamber intraocular
      lens implantation. The patient presented with a painful eye and increasing
      vertical diplopia. To our knowledge, neither the association of SINS and
      ankylosing spondylitis nor vertical diplopia as its presenting complaint has been
      described.

PMID- 10198873
TI  - [Red-green, the talk of the year. Germam ophthalmologists after the celebration].

PMID- 10198874
TI  - [Pre- and postoperative care in strabismus surgery].

PMID- 10198875
TI  - [The excitotoxicity theory of glaucoma].
AB  - Glaucoma can be defined as a disease in which one of the pathophysiological
      consequences of raised intra-ocular pressure is damage of the optic nerve, and
      subsequently the loss of retinal ganglion cells (RGCs). One of the main aims of
      modern glaucoma therapy is to alter the intraocular pressure, either surgically
      or pharmacologically. Recently it was shown that the vitreous of glaucoma
      patients contains increased levels of glutamate (27 microM as compared to 11
      microM in controls). This concentration of glutamate is sufficient to induce
      retinal ganglion cell death. The rise in intraocular pressure is probably the
      initial insult, which enhances the increase or release of glutamate. Although the
      increase in intravitreal glutamate levels is an accompanying feature of glaucoma,
      it could contribute to the loss of retinal ganglion cells in humans itself.
      Therefore, despite efficient control of intra-ocular pressure, RGC's loss will
      continue resulting in further visual impairment, if the toxic effect of glutamate
      is not blocked. If it would be possible to understand the mechanism leading to
      excessive vitreous levels of glutamate in glaucoma or to block its toxic effects,
      then the resulting visual loss could be retarded. This review discusses various
      proposed mechanisms leading to intraocular glutamate toxicity and the role of
      neuroprotection in this disease. (Literature search by Medline).

PMID- 10198876
TI  - [Confocal microscopy in corneal dystrophies].
AB  - BACKGROUND: Confocal microscopy represents a methodology that allows in vivo
      examination of corneal morphology, particularly of the epithelium and stroma.
      MATERIAL AND METHODS: Using the confocal microscope "ConfoScan Modell P2"
      epithelial, stromal and endothelial changes were evaluated in 11 patients with
      corneal dystrophies. All findings were compared with data from healthy
      individuals. RESULTS: Confocal images could be correlated to conventional
      (slitlamp) biomicroscopic findings in all patients with corneal dystrophies. In
      addition, confocal microscopy provided more detailed images particularly of
      epithelial and stromal changes. CONCLUSION: Our data indicate that confocal
      microscopy provides information on living tissue that correlates with that
      obtained with conventional techniques on fixed and sectioned tissue.

PMID- 10198877
TI  - [Prevalence of systemic and ocular diseases in age-related cataract patients].
AB  - BACKGROUND: Cataract patients often display concomitant ocular and systemic
      diseases which may influence the decision between general and regional
      anesthesia. The aim of this study was to quantify co-morbidity of these patients
      and assess the influence of the two types of anesthesia an the anesthesiological
      risk on the frequency of intra- and post-operative complications and visual
      outcome. METHODS: In this prospective study, in patients scheduled for cataract
      extraction at the University Eye Hospital and Clinic of Ulm (tertiary eye care
      center) all systemic and ocular diseases as well as intra- and postoperative
      complications were analyzed. The prevalence of the co-morbidity in our patients
      was compared to other studies including age-matched controls. The
      anesthesiological risk was quantified using the classification scheme of the
      American Society of Anesthesiologists (ASA). RESULTS: Eighty-eight patients with
      a mean age of 70.4 +/- 11.7 years were analyzed. Sixty-one% of patients displayed
      systemic as well as ocular co-morbidity. Only systemic or ocular comorbidity was
      present in 32% and 5% of patients, respectively. Two% of patients exhibited
      neither ocular nor systemic comorbidity. In 61% of patients the surgery was
      performed in regional anesthesia and in 39% in general anesthesia. The prevalence
      of systemic and ocular co-morbidity as found in our study was significantly
      higher as compared to that in the general population of the same age. Visual
      improvement and the frequency of intra- and postoperative complications were
      independent on type of anesthesia and anesthesiological risk. CONCLUSIONS:
      Patients who were scheduled at our institution for cataract surgery exhibited a
      high frequency of ocular as well as systemic co-morbidity. This can be
      interpreted in such a way that patients with a high level of co-morbidity are
      referred to tertiary eye care centers for cataract surgery.

PMID- 10198878
TI  - [Severe ocular injuries caused by fishing equipment].
AB  - BACKGROUND: Severe ocular injuries due to fishing equipment are rare, almost
      exclusively involve the anterior segments of men, and bear a bad prognosis. We
      report on two men and one woman with different etiologies of accidents. PATIENTS:
      In two men (53 and 39 yrs. OD and OS) and one woman (27 yrs., OD) a choroidal
      rupture due to a lead weight and subsequent choroidal neovascularisation (1x),
      temporal and nasal scleral and retinal lacerations (2x) due to a fish pick and a
      fish hook were noted. A laceration of the m. rectus int. (1x), uveal and retinal
      prolapse (1x), traumatic aniridia and aphakia (1x), a 12 and a 15 mm
      corneoscleral perforation temporal and nasal resp. including a retinal
      incarceration, a giant retinal tear 270 degrees, and vitreous and subretinal
      hemorrhage were seen. SURGERY: Interventions included 2x tight wound closure, 3x
      ppv, retinotomies (1x) endolasercoagulation (3x), silicone oil instillation (3x),
      muscel refixation (1x), and posterior lens implantation (1x). Subsequent surgery
      were silicone oil removal (2x) and membrane peeling (1x). RESULTS: An anatomical
      reconstruction was achieved in all of the patients, and the best postoperative
      visual acuity was gained after 4-6 months (+6.0 sph (2x) = 0.5, and +4.0 sph (1x)
      = 0.3). Silicone oil was removed after 4 and 13 months resp. followed by hypotony
      and redetachments, in one patient with silicone oil in place vision remained
      stable for > 2 years up to now at 0.5. CONCLUSIONS: Accidents due to fishing
      equipment may result in lacerations and contusions and involve women as well as.
      Surgery for extensive lacerations and complications of choroidal ruptures may not
      be hopeless, however, the prognosis for subsequent interventions is not good.
      Indications to remove silicone oil in eyes bearing a relative ciliary body
      insufficiency due to a long-standing insufficient wound closure should be done
      very cautiously.

PMID- 10198879
TI  - [Anisomyopia and myelinated nerve fibers--a syndrome].
AB  - BACKGROUND: The combination of anisomyopia and myelinated nerve fibres of the
      higher myopic eye is often correlated with a deep and therapy-refractive
      amblyopia. As the cause for the entity anisomyopia/myelinated nerve fibres a
      disorder of development on the level of the lamina cribrosa during embryo genesis
      has been suggested in the literature. There are only very few reports on a
      successful therapy of the amblyopia that goes along with anisomyopia/myelinated
      nerve fibres. PATIENTS: We report on six patients, aged 6 to 28 years, who
      presented with anisomyopia, myelinated nerve fibres and deep amblyopia in the
      higher myopic eye. The four younger patients were enrolled into a therapeutic
      trial with contact lens correction and occlusion. RESULTS: The six patients
      presented with varying degrees of anisomyopia between -3.5 D and -18.5 D. In
      addition, in two patients we found a microstrabism and in three patients an
      exotropia. In spite of consistent occlusion and full optical correction in the
      four patients who underwent therapy visual acuity did not improve to more than
      0.4 (1x microstrabism, 2x exotropia, 1x no squint--best visual recovery in the
      patient with microstrabism). CONCLUSIONS: The combination of unilateral high
      myopia and myelinated nerve fibres represents a special entity which usually is
      correlated with a deep amblyopia. The amblyopia is nearly refractive to therapy
      even under consequent therapy with contact lenses and prolonged occlusion.
      Nevertheless one should try to treat the amblyopia to achieve at least a small
      improvement. The goal is to diagnose this constellation already in the first two
      years of life. As our cases show occlusion therapy at this age can lead at least
      to a limited improvement of visual acuity.

PMID- 10198880
TI  - [Modified moisture chamber].
AB  - BACKGROUND: Moisture chambers can protect the eye in corneal lubrication or
      eyelid closure disorders. However, in cases with protrusio bulbi or pronounced
      chemosis conjunctivae direct damaging contact of the cornea or conjunctiva on the
      one hand and the inside of the moisture-chamber-bandage on the other hand are
      possible. Since commercial moisture-chamber-bandages are not available with
      different internal radii, new methods are necessary to increase the distance
      between the bandage and the eye. MATERIAL AND METHODS: A special pressure
      relieving foam dressing used in the therapy and prophylaxis of decubitus was
      prepared in such a way that a periocular attachment was enabled and an opening
      for the eye was left blank. This central opening was covered with a commercial
      moisture-chamber-bandage. Five test persons and two ventilated patients with
      protrusio bulbi and manifest lagophthalmus were treated with the modified
      moisture chamber. The relative humidity within the bandage was measured. RESULTS:
      The modified moisture chamber allows an individual adaptation to the periocular
      shape of the face and rises the level of the monoculus for about 7 mm. The
      internal relative humidity was for eight hours at 98% in both test persons and
      patients. All test persons felt more comfortable with the modified moisture
      chamber on their skin. CONCLUSIONS: The presented modified moisture chamber is a
      derivative of the commercial monoculus bandage for patients with sensitive
      protrusio bulbi.

PMID- 10198881
TI  - [New measuring method of non-contact tonometry].
AB  - BACKGROUND: The measuring value of intraocular pressure (IOP) in non-contact
      tonometry (NCT) depends on IOP and is additionally highly influenced by the
      biomechanical parameters of the cornea. These parameters (especially corneal
      thickness) differ among several patients. It is desirable to characterize this
      influence and to correct the measuring value during the IOP measurement. The new
      tonometer consists of an air pulse applicator generating an air pulse with a
      rampshaped rising and a sharp decay after switching off and a Michelson-type
      laserinterferometer for detecting the corneal movement during the air pulse
      application and the oscillation after switching off the air pulse. METHOD: The
      method was tested with a mechanical phantom eye. The pressure inside the chamber
      of the phanton is adjustable. Measuring surfaces, which have to simulate the
      shape and the elastic properties of the cornea, are made of soft silicon rubber
      and fabricated with different thicknesses. RESULTS: Measurement results show that
      both the rise of the corneal deformation and the damped oscillation (frequency
      and damping) depend from material thickness and internal pressure of the phantom
      eye. CONCLUSION: Thus a characterization of the influence of the mechanical
      properties and a determination of a corrected IOP-value are possible. The task at
      present is the investigation and formulation of the mathematical dependences.

PMID- 10198882
TI  - [Ocular bacteriosis in a patient with aplastic anemia].
AB  - BACKGROUND: For more than a century it has been recognized that bacteria may
      infect the eye by way of the blood stream. Until fifty years ago, eyes so
      afflicted nearly always were blinded and a majority of the victims died from
      overwhelming sepsis. Although effective antibiotics are available today the
      prognosis is still guarded. CASE REPORT: A 39-year-old physician died 6 years
      after he was diagnosed for idiopathic aplastic anemia. He had developed
      pseudomonas aeruginosa bacteremia and later a therapy refractive pneumonia caused
      by aspergillus which had led to respiratory failure. The patient had experienced
      a marked loss of visual acuity in his left eye ten days before he died.
      Ophthalmic examination at that point displayed signs of endophthalmitis,
      hyphaema, and heterochromic irises. The eyes were obtained postmortem and
      histologic examination of the left eye displayed numerous bacilli forming cuffs
      around blood vessels and a sheet between the necrotic retinal pigment epithelium
      and Bruch's membrane. No inflammatory response to the bacilli was present. The
      bacilli could be demonstrated with a Giemsa stain and could also be identified
      with electron microscopic examination. DISCUSSION: The histologic results in our
      patient displayed numerous bacilli without inflammatory reaction which was a
      result of the aplastic state. Therefore, this disease was classified as "ocular
      bacteriosis". The blood-ocular barrier undergoes direct assault with intraocular
      inflammation and the impermeability to blood-borne antibiotics is lost. However,
      with the lack of an inflammatory reaction the permeability to antibiotics may be
      too low and the achieved concentration insufficient.

PMID- 10198883
TI  - [Eye movement abnormalities as a sign for the diagnosis in Niemann-Pick disease
      type C].
AB  - BACKGROUND: Eye movement abnormalities in familial mental retardation syndrome
      should lead to the suspicion of a storage disorder, including Niemann Pick
      disease type C, Gaucher's disease, abetalipoproteinemia and Wilson's disease. The
      eye movement abnormalities in our two patients were suggestive of Niemann Pick
      disease type C, characterized by initial loss of voluntary vertical eye movements
      and subsequent loss of horizontal eye movements, with preservation of the
      vestibulo-ocular response. The characteristics of eye movements in storage
      disorders are different. In Gaucher's disease a progressive horizontal gaze
      palsy, in abetalipoproteinemia a particular type of internuclear ophthalmoplegia
      with nystagmus of the adducting eye and in Wilson's disease slowing of saccades
      may be observed. PATIENTS: We evaluated two mentally retarded sisters with
      unclear diagnosis at the age of 34 and 27 years. At the age of 24 and 21 a
      vertical gaze palsy led to the diagnosis of Parinaud syndrome. RESULTS: At the
      time of our examination both sisters were unable to perform voluntary horizontal
      or vertical saccades or pursuit eye movements. The vestibulo-ocular reflex was
      present in all directions. Optokinetic nystagmus and convergence were absent.
      This clinical picture led us to a suspicion of Niemann-Pick disease type C,
      confirmed by the presence of sea-blue histiocytes in the bone marrow biopsy.
      CONCLUSION: These cases demonstrate that the pattern of eye movement disorders in
      some syndromes associated with mental retardation can give important clues in the
      determination of the diagnosis.

PMID- 10198884
TI  - [Eccrine spiradenoma of the eyelid].
AB  - PATIENT: A 60-year-old woman was evaluated for a nodular tumor in her right upper
      eyelid, which has developed over the last four years. The tumor measured 10 x 8
      mm and was ulcerated. The patient's ophthalmologic und medical history was
      normal. Clinically, a basal cell carcinoma was suspected, and an excision was
      carried out under local anaesthesia. The histopathology was suggestive for an
      eccrine spiradenoma. CONCLUSION: Eccrine spiradenomas rarely involve the eyelids.
      This tumor represents a benign, usually painful, sweat gland tumor. The
      possibility of sweat gland tumor should be kept in mind in the diagnosis of
      eyelid tumors. The complete excision is the only therapeutic option.

PMID- 10198885
TI  - [Hoffmann PC, Hut WW, Echardt HB, Heuring A: IOL-calculations and ultrasonic
      biometry: Immersion and contact procedures. (Klin Monatsbl Augenheilkd
      1998;213:162-5)].

PMID- 10198886
TI  - [Medical-technological equipment of nonphysician monitoring of health status].
AB  - Extrahospital monitoring of the body's status is an effective method for health
      promotion of man and the general population. The paper presents medical
      engineering rationale for the software of health monitoring under different
      conditions, identifies three base-line configurations of these complexes: for use
      in health institutions: for that in the institutions lacking permanent medical
      staff; for individual and familial use.

PMID- 10198887
TI  - [Status and prospects of the development of anesthesia-respiratory equipment].
AB  - Anesthesia-respiratory equipment (ARE) mainly including assisted ventilation
      apparatuses, inhalation anesthesia apparatuses, as well as the monitors employed
      in the use of these apparatuses are and will be the lead on the market of medical
      equipment in Russia. Therefore it is important to consider the immediate
      prospects of ARE development. For each of the above three types of ARE, the paper
      briefly lists the current and promising applications, the sites of their use,
      procedures, principal quantitative requirement and design. It refers to the most
      specific Russian and foreign items. The authors outline their own views of the
      immediate tasks of ARE design in Russia.

PMID- 10198888
TI  - [The protective signalization of human vital functions: methodology, concept,
      devices].
AB  - The paper describes a basically new approach to solving the most pressing
      sociomedical approach, i.e. timely rendering a medical aid when acute vital
      dysfunctions suddenly occur in real daily life. A new concept of medical
      instrument making for human life and health protection has been developed on the
      basis of the theory of functional systems which discloses the universal
      mechanisms of self-regulation of the body's function. Its practical application
      is the design and patent a number of original devices of the protective
      signalling system which may be classified as information microprocessor devices
      designed for daily individual continuous control and notification of the first
      objective signs of physiological dysfunctions.

PMID- 10198889
TI  - [Development of instrumental technologies of assessment of higher mental
      functions in health and disease].
AB  - The current increase in the incidence of nervous and mental diseases makes it
      necessary to use monitoring means for dysfunctions of the central nervous system.
      The paper analyzes promising ways of development of medical engineering
      technologies for studies, diagnosis, and rehabilitation in higher mental
      dysfunctions. Particular emphasis is laid on the instrumental methods for
      examining the higher nervous performance and relevant technical means.

PMID- 10198891
TI  - [Laser mass spectrometric analysis of biomedical samples using basic and second
      harmonics of yttrium-aluminum-garnet laser].
AB  - Laser mass spectrometric analysis of a biomedical sample was made on exposure to
      laser radiation at lambda 2 = 532 nm. The parameters of laser radiation and mass
      spectra were comparatively analyzed by using the basic and second harmonics of
      aluminum-yttrium-garnet-based laser. The sensitivity of laser mass spectrometry
      of biomedical samples is increased.

PMID- 10198892
TI  - [Theoretical bases and software application of planimetric analysis of real-time
      cardiac signals].
AB  - The paper presents an algorithm of partial and complete morphological analysis of
      cardiac signals in real time. Linear selective transformation is the key
      procedure that precedes and creates prerequisites for morphological analysis of
      cardiac signals in real time.

PMID- 10198890
TI  - [Equipment for hemodialysis using biologically active dialyzing solutions].
AB  - The paper describes the test specimen of an apparatus for performing hemodialysis
      and ultrafiltration using biologically active dialysates. The designed test
      specimen may serve as a technical base for further investigations and
      optimization of hemodialysis using a biologically active dialysate.

PMID- 10198893
TI  - [Possibilities of enhancing the effectiveness of electrosurgical effects].
AB  - To enhance the efficiency of electrosurgical exposures is a highly topical task.
      The paper deals with the aspects of enhancing the efficiency by optimizing the
      basic parameters of electro-surgical equipment and by combining various energy
      exposures for surgical tissue.

PMID- 10198894
TI  - [Construction of pulse oximeters based on sigma-delta transducers].
AB  - The method of continuously measuring arterial blood saturation (pulse oximetry)
      has been recently intensively developed. The paper proposes a new schematic
      design of pulse oximeters based on the current multiple-digit sigma-delta
      transducers which reduces expenses connected with device operation, simplifies
      the regimen and algorithms of control, increases the quality of data reading.

PMID- 10198895
TI  - [Chaotic dynamics in arrhythmias].
AB  - The paper proposes the systematization of cardiac arrhythmias in accordance with
      a generalized scheme of transition from regular conditions to random changes,
      which makes it possible to conclude that the occurrence of more menacing
      arrhythmias in patients with implantable pacemakers may suggest that there is a
      risk for random disorders, as well as to recommend to change pacing parameters
      and even to replace the pacemaker. At present the authors are conducting computer
      aided studies of the proposed approach in the Matlab medium. The algorithm of
      search for the facts of complication of the dynamic behavior of the system is
      based on the odd set theory which is presently most promising for designing
      cardiological monitoring systems. The new approach suggests that there are
      changes in the dynamics of arrhythmias and hence it will be of practical value in
      treating all cardiological patients.

PMID- 10198896
TI  - [An expert system to support diagnostic decision making by a neonatologist].
AB  - An "NATEX" expert system has been designed, which is intended to support a
      neonatologist's diagnostic decision making at the first stage of neonatal
      nursing. While designing the expert system, the authors used the shell
      "REPROCODE" wherein medical knowledge is presented as hierarchical semantic
      threshold network with shared attribute space. The designed system is realized on
      the basis of an IBM PC XT/AT, its operation requires only the processor 80286 and
      the operating system MS DOS 3.0 or higher. The "NATEX" expert system is employed
      to diagnose major syndromes of neonatal diseases. The knowledge base of the
      "NATEX" system has an account of 33 syndromes of neonatal diseases and, with
      various forms of severities borne in mind, the total number of diagnosed
      conditions in a baby is 63. In terms of content, it covers all major syndromes
      assessing the vital systems of the neonatal body and their occurring processes.
      The total number of symptoms which are necessary and sufficient for making a
      diagnostic decision as realization of either syndromes is 700.

PMID- 10198897
TI  - [Blood coagulation analyzer].
AB  - A ten-channel coagulometer has been designed. Its operation principle is based on
      the clotting method using a monitoring ball and magnetic transducers. The
      coagulometer consists of a recording unit and a unit of a thermostatic switch and
      a ball dosing apparatus. The device may operate off-line or may be connected to a
      personal computer. It has a specialized software and a medical manual. The
      analyzer may be used in clinical diagnosis laboratories for coagulation tests.

PMID- 10198899
TI  - [Cochlear implant today and auditory brainstem implant in the future].

PMID- 10198898
TI  - [Metrological aspects of the study of physical characteristics of the air on the
      objects in the vicinity of the habitat].
AB  - The paper considers the problems of measurement of air ions for settle the tasks
      of medical and environmental monitoring the habitat of various objects. It
      discusses the metrological assessment of the physical characteristics of the
      environment and the reasons for the insufficient use of aeroionometry in public
      health. The paper also compares the characteristics and specific features of the
      use of devices intended for study of air ion spectra. It shows it necessary to
      design the devices that measure air ions, which satisfy with the requirements
      that they measure accurately, are easy-to-use, rapidly operate.

PMID- 10198900
TI  - [Alzheimer disease and cholesterol].

PMID- 10198901
TI  - [The clinical usefulness of high-dose intravenous immunoglobulin therapy for
      chronic inflammatory demyelinating polyneuropathy and multifocal motor
      neuropathy].
AB  - To explore the optimum dose of intravenous immunoglobulin (i.v.Ig) for treating
      patients with chronic inflammatory demyelinating polyrneuropathy and multifocal
      motor neuropathy, we compared the usefulness of i.v.Ig among 3 treatment doses.
      Fifty-nine patients were randomly divided into three treatment dosage groups: 20
      patients for Group I using 50 mg/kg/day x 5 days, 19 patients Group II using 200
      mg/kg/day x 5 days, and 20 patients Group III using 400 mg/kg/day x 5 days. We
      assessed clinically and electrophysiologically the effectiveness of the treatment
      at 5 weeks after the initial infusion. For patients in Group I and II who had not
      improved (or worsened) with the first treatment, we gave a one-step larger dose
      in the second treatment (i.e. 200 mg/kg/day x 5 days for those who had been given
      50 mg/kg/day x 5 days, 400 mg/kg/day x 5 days for those who had been given 200
      mg/kg/day x 5 days) after more than 9 weeks. We found that 15% of the patients in
      Group I, 21% in Group II and 60% in Group III improved dose-dependently with the
      first intravenous immunoglobulin treatment. Seven (47%) of 16 patients in Group I
      and 4 (40%) of 11 patients in Group II improved after the second treatment with
      larger doses. Adverse reactions including chill sensation, fever, skin eruption
      and increase in blood GOT and GPT levels were transient and mild. One patient in
      Group III developed left hemiparesis showing the small infarction in the right
      thalamus during the course of the treatment, but the symptom was mild. In
      conclusion, the high-dose intravenous immunoglobulin therapy (400 mg/kg/day x 5
      days) is useful for treating patients with CIDP and MMN, although care must be
      taken of the risk of causing cerebral infarctions.

PMID- 10198902
TI  - [Reassessment of the Luria's fist-edge-palm test].
AB  - In clinical practice, we often use the Luria's fist edge-palm test (FEP) to
      detect frontal lobe dysfunction. However, we have sometimes encountered patients
      with failure in this test following posterior lesions. The aim of our study is to
      evaluate the sensitivity of this test to frontal lobe damage and to clarify the
      relationship between the FEP performance and other neuropsychological findings.
      Forty brain-damaged patients (mean age: 61.7 years) were studied. Thirty-four
      patients were right-handed and 6 non right-handed. Their lesions were confirmed
      by CT or MRI scan. Following six tests were performed; 1) imitation of single
      hand posture, 2) imitation of a sequence of two hand postures (fist-edge), 3)
      imitation of a sequence of three and postures (FEP), 4) copying a cube, 5) serial
      drawing, and 6) verbal and non-verbal short-term memory span. Imitation of hand
      postures were performed with non-paralytic hand. Twenty-four patients, i.e., 60%
      of the patients tested, failed to perform the FEP sequence. The failure was
      significantly correlated with the presence of constructional disability,
      perseveration and short-term memory impairment. There was significant
      relationship between the failure the FEP and frontal lobe damage. However, we
      found five patients without frontal lesion who failed in performing the FEP. We
      conclude that we should be careful in associating the failure in the FEP with
      frontal lobe damage, although this test is sensitive to brain dysfunction.

PMID- 10198903
TI  - [A case of medial medullary syndrome detected by diffusion-weighted magnetic
      resonance imaging].
AB  - We report an 84-year-old woman with medial medullary syndrome diagnosed by
      diffusion-weighted magnetic resonance imaging (MRI). She was admitted because of
      left hemiparesis and hypesthesia. T2-weighted and diffusion-weighted MRI showed a
      high signal lesion at the right medial medulla oblongata 10 days after the onset.
      It is well known that diffusion-weighted MRI is useful for detecting
      supratentrial cerebral ischemic lesions in the extremely acute stage. However, to
      our knowledge, there have been only a few reports of diffusion-weighted MRI in
      patients with ischemic stroke of the medulla oblongata. Normal nerve fibers in
      the direction perpendicular to the motion-probing gradient (MPG) shows a high
      signal by diffusion-weighted MRI (anisotropy of apparent diffusion cofficient
      [ADC]). Normal nerve fibers in the pyramidal tract of medulla oblongata also
      shows a high signal when the MPG pulse is applied in the x and y directions. We
      solved this problem by using isotropic diffusion-weighted imaging and were able
      to detect ischemic lesion of medial medullary infarction in the acute phase.

PMID- 10198904
TI  - [A case of cerebral juvenile pilocytic astrocytoma: observation of the
      development of the tumor].
AB  - A case with cerebral juvenile pilocytic astrocytoma (JPA) was reported. The
      patient was 33-month-old boy, who developed headache and loss of activity on
      December, 1994. Although he was indicated macrocephaly at the age of just 1 year,
      CT scan showed no abnormality at that time. On admission, MRI revealed multiple
      large cysts with an enhanced mural nodule in the left frontal lobe. The tumor was
      totally removed, and histologically diagnosed as JPA, because of alternating two
      types of structures of loose knit tissue composed of satellite astrocytes and
      compact tissue consisting of highly fibrillate cells. MIB-1 percent positivity
      was almost negative. We summarized and discussed the clinicopathological and
      proliferating characteristics of the cerebral JPA. These considerations suggested
      that the tumor already existed at the age of 1 year and developed during these 20
      months, according to the theory that the growth rate of JPAs is programmed to
      slow down as the patient grows.

PMID- 10198905
TI  - [A case of superficial siderosis of the central nervous system--findings of the
      neuro-otological tests and evoked potentials].
AB  - We report a 57-year-old woman with superficial siderosis of the central nervous
      system. On physical examination, sensorineural hearing impairment, cerebellar
      ataxia, pyramidal tract signs, dysarthria, and neurogenic bladder were seen.
      Brain and spinal cord MRI (T2 and proton weighted images) revealed cerebellar
      atrophy and marginal hypointensity of the Sylvian fissure and brain stem,
      cerebellum and spinal cord. We diagnosed this patient as superficial siderosis
      because of the clinical course and specific findings on MRI. We consider this
      case idiopathic superficial siderosis because the source of the bleeding was
      unknown. Neuro-otological tests and BAEP disclosed retrocochlear deafness. Her
      central motor conduction time on MEP was delayed. We discussed the pathogenic
      mechanism of these conditions, and we concluded that we must take notice of
      myelinopathy in superficial siderosis and that MEP was useful for detecting them.

PMID- 10198906
TI  - [Two cases in which the presence of ciliospinal response led to indecisiveness in
      the evaluation of brain death].
AB  - The ciliospinal reflex was first described by Budge in 1852. This reflex is used
      as an indicator of brain stem and autonomic nervous system functioning. In the
      Japanese guideline for determining brain death, the absence of this reflex is
      considered essential. We reported two cases in which the ciliospinal responses
      judged to be present resulted in the authors' indecision in determining brain
      death. They were the cases of a 74-year-old woman who suffered a right putaminal
      hemorrhage and that of a 28 year-old male with severe head and cervical cord
      injury. Although brain death was suspected in both cases from its clinical
      courses, the fact that the ciliospinal reflex was present in each case kept us
      from declaring that these patients were in the state of brain death. The center
      of the ciliospinal reflex lies in the first three segments of the thoracic spinal
      segments and two pathways are involved in this reflex. A noxious stimulation to
      the face will be registered through the brain stem, but if stimulation is in the
      neck or upper trunk, it may go directly to the spinal center. Because of the
      latter pathway to the spinal center, this reflex might remain in patients in whom
      the brain stem is completely nonfunctioning. Therefore, the presence of this
      reflex dose not always preclude a state of brain death.

PMID- 10198907
TI  - [A sporadic case of spinocerebellar ataxia 6 (SCA 6) with large CAG expansion of
      the CACNL1A4 gene].
AB  - We reported a 73-year-old woman of spinocerebellar ataxia 6 (SCA 6). There was no
      family history of neurological diseases. She demonstrated cerebellar ataxia and
      scanning speech at the age of 48. These symptoms gradually developed. Brain MRI
      showed severe cerebellar atrophy and no abnormality in the brain stem. Her
      neurological symptoms and MRI findings were compatible with cerebellocortical
      atrophy (CCA). Analysis of the CACNL1A4 gene on chromosome 19p 13 demonstrated
      she had an expanded allele with 27 CAG repeats. Therefore, she was diagnosed with
      SCA 6. In spite of her large CAG expansion, there was no family history of SCA 6
      in this case. SCA 6 needs to be ruled out in cases of clinical CCA.

PMID- 10198908
TI  - [A case of pure agraphia with a deficit of drawing].
AB  - We examined a drawing ability in a case with pure agraphia. The patient, having
      lesions in the left middle frontal gyrus and inferior parietal lobule, could not
      write in both dictation and spontaneous writing tasks, with the ability to copy
      letters being well spared. Correspondingly, he showed a deficit of spontaneous
      drawing, with the ability to copy complex figures being well spared. These
      findings suggest that he could have an impairment of retrieving visual image, not
      restricted to letter image. Although some previous cases with pure agraphia were
      attributed to an impairment of retrieving visual letter image, drawing ability
      which seemed to be related to retrieving visual image had not been investigated.
      In the present case, disability of both writing and drawing could be attributed
      to a common mechanism, that was an impairment of retrieving visual image. In
      addition, the patient did not show a significant difference between the
      performance on Kana writing and on Kanji writing. But it has been said that an
      impairment of retrieving visual letter image could be related to a deficit of
      Kanji writing more than of Kana writing. Then, it could be assumed that the
      mechanism of Kana writing involved not only the pathway depending on graphical
      motor pattern but one depending on visual image.

PMID- 10198909
TI  - [High intensity cortical lesion on T1-weighted image in cerebral infarction].

PMID- 10198910
TI  - [A 40-year-old woman with progressive dementia and abnormal behavior].
AB  - We report a 40-year-old Japanese woman who died after 12 years history of
      progressive dementia and abnormal behaviors. She was well until 1985 at her age
      of 28 years old, when she had an onset of behavioral change in which she drank
      much, neglected house-keeping works, and her life style became sloppy. At age 30,
      she became unable to understand written sentences, and paced up- and down in and
      out of her house. She was admitted to other hospital where marked dementia with
      disorientation and memory loss were noted. Slight increase in CSF protein and
      decrease in the peripheral nerve conduction velocity were also noted at that
      time. In the next year, she started to have convulsions. These symptoms had
      progressively become worse and was admitted to Tokyo Metropolital Matsuzawa
      Hospital in June of 1991 when she was 34 years of age. Despite marked dementia,
      she was able to walk normally, no motor paralysis, cerebellar ataxia, nor
      dyskinesia were noted. Deep tendon reflexes were diminished. MRI revealed T-2
      high signal intensity lesions involving the white matter of the cerebrum
      predominantly in the frontal region. In about one year, she started to show
      difficulty in gait, and she became bed-ridden in July of 1994. She was discharged
      to home for a while, but required admission again. She expired on February 5,
      1998. Her younger brother had an essentially similar dementing disease and he
      expired at the age of 35 years. The parents were of first cousins. The patient
      was discussed in a neurological CPC, and the chief discussant arrived at the
      conclusion that the patient had adult form of metachromatic leukodystrophy,
      because of white matter change in the frontal lobe, decrease in nerve conduction
      velocity, convulsion, marked dementia, and consanguineous marriage with a
      similarly affected brother. Most of the audience agreed with this conclusion, but
      the differential diagnosis from globoid cell leukodystrophy was felt difficult
      from the clinical findings alone. Post-mortem examination revealed marked atrophy
      in the frontal lobe. Cerebellum appeared to be smaller than normal. In the
      coronal sections, marked atrophy of the white matter with brown discoloration was
      noted. The lateral ventricles were dilated. Kluver-Barrera staining revealed
      marked demyelination with relative preservation of the U-fibers. PAS-positive
      materials were deposited in some astrocytes as well as neurons. Metachromatic
      deposits were noted not only in the cerebrum but also cerebllum after staining
      with acid cresyl violet. Pathologic diagnosis was consistent with adult type of
      metachromatic leukodystrophy.

PMID- 10198911
TI  - Effect of large bowel fermentation on insulin, glucose, free fatty acids, and
      glucagon-like peptide 1 (7-36) amide in patients with coronary heart disease.
AB  - Insulin resistance syndrome has recently been described as a unifying hypothesis
      to explain the relationship between the many risk factors of coronary heart
      disease. Carbohydrate that is malabsorbed and fermented in the colon has been
      demonstrated to decrease insulin response to a glucose load and improve other
      risk factors associated with coronary heart disease, although the mechanism
      remains unclear. The object of the present study was to investigate whether this
      observation could be explained by the production of fermentation products induced
      by malabsorbed carbohydrate in the colon, or by stimulating the incretin glucagon
      like peptide 1 (7-36) amide that is released from the large bowel. We used
      lactulose as a model for resistant starch carbohydrate. Ten insulin-resistant
      male volunteers, who had undergone previous coronary artery bypass grafting,
      volunteered to take part in the study and underwent 6 d of lactulose loading (15
      g/d for 2 d and 30 g/d for 4 d). There was no significant change in insulin,
      glucose, free fatty acids, or glucagon-like peptide 1 (7-36) amide response to an
      oral glucose tolerance test following the lactulose despite a significant rise in
      breath hydrogen. Large bowel fermentation stimulated by lactulose appears to have
      no significant effect on insulin, glucose, free fatty acids, and glucagon-like
      peptide 1 (7-36) response in patients with coronary heart disease.

PMID- 10198912
TI  - Whole body protein turnover in children with human immunodeficiency virus (HIV)
      infection.
AB  - The purpose of this study was to determine the rate of whole body protein
      turnover (WBPT) in human immunodeficiency virus (HIV)-infected children, and to
      determine the relationship between WBPT and growth. The rate of WBPT was
      calculated from the cumulative excretion of labeled urinary ammonia after a
      single intravenous dose of 15N-glycine in three groups of children: 1) HIV+ with
      growth retardation (HIV+ Gr); 2) HIV+ with normal growth (HIV+); and 3) HIV
      uninfected with normal growth (HIV-). Twenty-six children between 2 and 11 y of
      age were studied (10 HIV+ Gr, 12 HIV+, 4 HIV-). All children were afebrile and
      free of acute infection during the study. Rates of WBPT (mean +/- SD) for the
      study groups were: HIV+ Gr, 12.2 +/- 4.8; HIV+, 10.7 +/- 5.1; and HIV-, 8.6 +/-
      2.1 g.protein.kg-1.d-1 (NS, P > 0.05). Although not statistically significant,
      mean WBPT was 42% greater in HIV+ Gr, and 24% greater in HIV+ compared to HIV-.
      Statistically significant correlations were found between WBPT and Z scores for
      height (r = -0.39, P = 0.05) and weight-for-age (r = -0.51, P = 0.01) and dietary
      intake of protein (r = 0.39, P = 0.05), and between protein balance (synthesis
      catabolism) and intakes of energy (r = 0.47, P = 0.02) and protein (r = 0.40, P =
      0.04). There was no statistically significant correlation between WBPT and
      resting energy expenditure (r = 0.27, P = 0.19), or CD4 cell number (r = 0.05, P
      = 0.82). These data suggest an association between increased rates of protein
      turnover and low weight and height-for-age Z scores, and that it may be possible
      to achieve positive protein balance given an adequate intake of nutrients.

PMID- 10198913
TI  - Plasma amino acid concentrations in patients with acute myelogenous leukemia.
AB  - Changes in plasma-free amino acid (PFAA) concentrations in the presence of solid
      tumors have been widely described. Conversely, the PFAA profile in patients with
      acute leukemias is less well defined. The aim of the present study was to clarify
      whether the PFAA profile is altered in patients with acute myeloid leukemia
      (AML), whether the profile differs from the PFAA profile of solid tumors, and
      whether it may predict outcome of AML. Fasting PFAA were measured in 40
      untreated, normally nourished patients with AML (17 males, 23 females), ages 22
      78 y, with white blood cell (WBC) counts ranging from 1.08 to 276.5 x 10(3)/cm2,
      and in 24 healthy volunteers. Plasma concentrations (mu mol/L, mean +/- SE) of
      glutamic acid (GLU), free tryptophan (FTRP), ornithine (ORN), and glycine (GLY)
      were significantly higher in AML (GLU: 90.2 +/- 6.1 versus 37 +/- 8; FTRP: 7.0 +/
      0.6 versus 4.8 +/- 0.3, P < 0.005; ORN: 108.7 +/- 5.8 versus 78 +/- 6, P <
      0.001; GLY: 295.0 +/- 14.8 versus 239 +/- 9, P < 0.01), whereas serine (SER),
      methionine (MET), and taurine (TAU) were significantly lower in AML than in
      controls (SER: 109.0 +/- 5.8 versus 130 +/- 4, P < 0.03; MET: 25.5 +/- 1.3 versus
      33 +/- 3, P < 0.03; TAU: 46.5 +/- 3.5 versus 81 +/- 2, P < 0.001), and tended to
      be even lower in patients who had not responded to chemotherapy or had relapsed
      within 18 mo of enrollment. Such changes were unrelated to age, sex, and WBC
      count. Changes in PFAA that occur in AML are only in part similar to those
      observed in solid tumors. The reduction of TAU appears to be a typical feature of
      AML and might be secondary to the deficiency of its precursors SER and MET.
      Further studies are under way aimed at clarifying whether PFAA might predict
      prognosis in AML, whether PFAA is normalized by remission induction, and if its
      correction may be of any benefit for patients with hematologic malignancies.

PMID- 10198914
TI  - Mouse extensor digitorum longus muscle preparation as a tool in nutrition
      research: a quantitative comparison to in vivo and cell culture experiments.
AB  - Incubated restrained and unrestrained extensor digitorum longus (EDL) muscles
      from adult non-growing mice were evaluated as a tool in non-steady state
      nutrition experiments. Energy state was determined by nucleotide determinations
      in muscles. Protein synthesis was estimated by the amount of L-[U
      14C]phenylalanine incorporated into proteins, and protein balance was measured by
      tyrosine release from muscle proteins. Confluent cultured L6 rat muscle cells
      served as a reference system in steady state without hypoxia being sensitive to
      growth factors and regulatory peptides at physiologic concentrations.
      Irrespective of medium composition, incubated EDL muscles remained in negative
      protein balance, being unrelated to the resting tension of the incubated muscles.
      Energy-rich phosphates were not restored to normal levels during incubation, but
      protein synthesis was not attenuated by the decline in energy state. Fractional
      protein synthesis (0.05-0.15%/h) remained constant for up to 6 h of EDL
      incubation, and was comparable to protein synthesis in cultured confluent non
      proliferating myocytes (0.20-0.30%/h) and to mixed leg muscles measured in vivo
      (0.10-0.20%/h). Protein synthesis in incubated EDL muscles reflected alterations
      in muscle peptide formation in vivo following either oral provision of food or
      parenteral injection of insulin. EDL muscles were sensitive to in vitro exposure
      to both insulin (60-125 microU/mL) and insulin-like growth factor 1 (IGF-1) (1000
      ng/mL). The sensitivity to insulin seemed to be modified by the nutritional state
      (starved/fed) of the animals before sacrifice. Protein synthesis in EDL muscles
      was less responsive to serum-containing growth factors (IGF-1, epidermal growth
      factor [EGF], platelet-derived growth factor [PDGF]) compared to confluent L6
      muscle cells, which probably reflected different receptor expression. Our results
      demonstrate that protein metabolism in incubated unrestrained mouse EDL muscles
      reflects in vivo protein metabolism.

PMID- 10198915
TI  - Differential effects of dietary Oenothera, Zizyphus mistol, and corn oils, and
      essential fatty acid deficiency on the progression of a murine mammary gland
      adenocarcinoma.
AB  - The modulating effect of dietary enrichment in mistol seed oil (MO) containing
      25% of alpha-linolenic acid (ALA), evening primrose oil (EPO) enriched in gamma
      linolenic acid (GLA) and corn oil (CO) as sources of omega-6 and omega-9 fatty
      acids on the growth parameters of one transplantable mammary tumor were compared.
      Mice fed on different lipid formulae were inoculated with a mammary gland
      adenocarcinoma and different growth development tumor parameters were recorded.
      Results showed that corn oil feeding slowed down most of the tumor growth
      parameters, as did the EPO diet. MO also showed antitumor activity. Olein
      feeding, which induces an essential fatty acid deficiency (EFAD), increased the
      incidence and the multiplicity of metastases when compared with the controls. It
      may be concluded that a diet enriched in omega-6 fatty acids did not behave as a
      tumor promoter in this mammary gland tumor model. The antitumor activities of EPO
      and MO are corroborated in present experiments, suggesting that both oils may be
      of value in nutritional approaches of mammary gland tumor therapies. In addition,
      present data add further experimental proof about the proposed protumorigenic
      proneness induced by the EFAD state.

PMID- 10198916
TI  - Changes of liver-enriched nuclear transcription factors for albumin gene in
      starvation in rats.
AB  - The regulatory mechanism of albumin gene transcription was examined using male
      Donryu rats (7 wk old) starved for 1 or 3 d. At the designated times, the rats
      were sacrificed to harvest the liver and to measure the serum albumin level.
      Neither the serum albumin nor the albumin messenger RNA (mRNA) level showed a
      significant change for these starvation periods. Among nuclear factors binding to
      the D site of albumin gene promoter, the CCAAT/enhancer binding protein alpha
      (C/EBP alpha) mRNA level showed a decrease and the D site binding protein (DBP)
      mRNA level tended to decrease after 3 d of starvation. In contrast, the C/EBP
      beta mRNA level showed a significant increase at day 1. As a B site binding
      nuclear factor, the hepatocyte nuclear factor 1 (HNF-1) mRNA level significantly
      increased at day 1. Gel mobility-shift analysis combined with Western
      immunoblotting confirmed the presence of D site binding proteins composed of DBP
      and C/EBP alpha and beta in both groups subjected to oral feeding and to 3-d
      starvation, though quantitative analysis could not be done. In conclusion, the
      nuclear transcription factors binding to the albumin gene promoter undergo
      regulatory changes during 3 d of starvation, whereas there is no significant
      decrease in the albumin mRNA level.

PMID- 10198917
TI  - Chronic vitamin E deficiency causing spinocerebellar degeneration, peripheral
      neuropathy, and centro-cecal scotomata.

PMID- 10198918
TI  - Nutritional support in hepatic encephalopathy.
AB  - Hepatic encephalopathy (HE) is a syndrome of global cerebral dysfunction
      resulting from underlying liver disease or portal-systemic shunting. HE can
      present as one of four syndromes, depending on the rapidity of onset of hepatic
      failure and the presence or absence of preexisting liver disease. The precise
      pathogenesis is unknown but likely involves impaired hepatic detoxification of
      ammonia as well as alterations in brain transport and metabolism of amino acids
      and amines. The etiology of malnutrition in hepatic failure is multifactorial.
      Nutritional deficits may be clinically manifest as marasmus or kwashiorkor, or
      both. Nutritional support in HE is directed toward reducing morbidity related to
      underlying malnutrition and concurrent disease. However, reaching nutritional
      goals is often complicated by protein and carbohydrate intolerance. The use of
      protein restriction in HE is controversial. Modified formulas that are
      supplemented in branched chain amino acids may be of value in patients who
      exhibit protein intolerance with standard feeding solutions or in patients who
      present with advanced degrees of encephalopathy.

PMID- 10198919
TI  - Taste aversion learning: a contemporary perspective.
AB  - Food aversion learning has attracted widespread interest because it is a highly
      adaptive, powerful type of learning with both practical and theoretical
      ramifications. It has features that make it unusual and robust when compared with
      other learning paradigms. It has relevance to human problems in that it is likely
      to contribute to food choice and appetite problems in certain clinical
      situations. And the robustness of this learning makes it a promising model for
      neurobiologists interested in understanding neural mechanisms of plasticity. This
      review provides a broad overview of these aspects of taste aversion learning and
      points to areas where questions remain and additional research is needed.

PMID- 10198920
TI  - Mexican consensus on the integral management of digestive tract fistulas. Ixtapa
      Zihuatanejo, Mexico, August 21-23, 1997.

PMID- 10198921
TI  - Essential fatty acids and their metabolites and cancer.

PMID- 10198922
TI  - The protein synthetic response to feeding: a fundamental question revisited.

PMID- 10198923
TI  - Impact of cholesterol on cardiovascular morbidity and mortality in older adults.

PMID- 10198924
TI  - A nutritional component to inflammatory bowel disease: the contribution of meat
      to fecal sulfide excretion.

PMID- 10198925
TI  - Role of enteral nutrition-induced splanchnic hyperemia in ameliorating splanchnic
      ischemia.

PMID- 10198926
TI  - The regulatory status of medical foods and dietary supplements in the United
      States.

PMID- 10198927
TI  - Problems with lines and the pharmacist's role.

PMID- 10198928
TI  - Just 40 years ago.

PMID- 10198929
TI  - Respecting pregnant women's treatment choices.

PMID- 10198930
TI  - Automated cervical cytology: meta-analyses of the performance of the PAPNET
      system.
AB  - Our objective was to assess current knowledge regarding PAPNET (Neuromedical
      Systems, Inc.) automated cervical cytology screening methods and to assess the
      performance of this automated system in comparison with manual screening. To this
      goal, studies published in the English language regarding the PAPNET system,
      identified from a MEDLINE search through August 1998 were selected. Performance
      of the PAPNET system was assessed with various meta-analysis techniques, using
      the method of Mantel-Haenszel. In the primary screening modality, meta-analysis
      of the performance of the PAPNET system indicates that when compared with manual
      screening, the odds of obtaining a positive result were significantly greater.
      The Mantel-Haenszel odds ratio for combined studies was 1.19 (95 percent CI =
      1.13 to 1.26, P < .001), corresponding to 20 percent greater odds of positive or
      suspicious slides with PAPNET system. The PAPNET system performs with almost two
      fold less false-negative results. The Mantel-Haenszel odds ratio for combined
      studies was 0.41 (95 percent CI = 0.25 to 0.67, P < .005). Applied as a quality
      control modality rescreening all consecutive previously manually screened
      negative slides, depending on study design, the PAPNET system reclassified as
      abnormal between 0.1 and 5 percent. However, when the PAPNET system was used to
      rescreen known false-negative slides, PAPNET system rescreening can correctly
      identify between 20 and 90 percent of manually screened false-negative slides
      with an average reduction of 33 percent of the manually screened false-negative
      slides. We conclude that compared with manual screening, PAPNET identifies 20
      percent more abnormal, has two-fold less false-negative, and reclassifies as
      abnormal one third of manually screened false-negative slides. TARGET AUDIENCE:
      Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After
      completion of this article, the reader will be able to understand how the PAPNET
      system works and what is its approved use by the FDA, and to understand the
      associated benefits and shortcomings of the PAPNET system when compared with the
      traditional screening method.

PMID- 10198931
TI  - Deep vein thrombosis during pregnancy and the puerperium: a meta-analysis of the
      period of risk and the leg of presentation.
AB  - We performed a meta-analysis of all published studies of deep vein thrombosis
      during pregnancy and the puerperium using MEDLINE between 1966 and May 1998. Data
      were pooled using a random effects model. Fourteen studies included relevant
      information on deep vein thrombosis in pregnancy or the puerperium, and used
      objective testing to diagnose deep vein thrombosis. The pooled event rate for
      left sided or bilateral deep vein thrombosis was 82.2 percent (95 percent CI 75.1
      to 87.5). There was no statistical evidence of heterogeneity for this figure (P =
      .08). Twelve studies reported on the trimester in which deep vein thrombosis was
      diagnosed. The deep vein thrombosis event rate during the first trimester was
      21.9 percent (95 percent CI 17.4 to 27.3), 33.7 percent (95 percent CI 28.1 to
      39.8) during the second trimester, and 47.6 percent (95 percent CI 39.2 to 56.2)
      for the third trimester. Heterogeneity testing was not significant. Nine studies
      compared deep vein thrombosis events between the antepartum and puerperium
      periods, with 65.5 percent (95 percent CI 58.1 to 72.1) arising during pregnancy,
      and 34.5 percent (95 percent CI 27.9 to 41.9) postpartum (P = .08, not
      heterogeneous). Using these figures, the estimated relative distribution of 100
      deep vein thrombosis events during pregnancy and the puerperium would be 0.23 per
      day during pregnancy, and 0.82 per day in the postpartum period. During pregnancy
      and the puerperium, deep vein thrombosis is more likely to arise in the left leg.
      More than half of all deep vein thromboses during pregnancy occur during the
      first and second trimesters. Furthermore, during the puerperium, the risk of
      developing deep vein thrombosis is significantly higher than antepartum. TARGET
      AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES:
      After completion of this article, the reader will be able to understand the
      incidence and distribution of DVTs during pregnancy and to be able to appreciate
      the differing risk of DVT during the various time periods in a pregnancy.

PMID- 10198932
TI  - Tamoxifen effects on menopause--associated risk factors and symptoms.
AB  - This study reviewed the available data on the influence of prolonged tamoxifen
      treatment on postmenopausal women. Tamoxifen might induce or increase vasomotor
      symptoms, such as hot flushes and night sweats, and occasionally cause vaginal
      discharge, irritation, and bleeding. Long-term use of tamoxifen by premenopausal
      women lowers total serum cholesterol and LDL-cholesterol, with a resultant
      reduction in cardiovascular mortality. In postmenopausal women, tamoxifen has a
      similar effect on serum lipids, but its cardioprotective effect has not yet been
      substantiated. Tamoxifen has a beneficial effect on bone density presumably
      through its estrogen agonistic effects. It has an antiresorptive action primarily
      on trabecular bone and to a lesser extent on cortical bone, thus preserving bone
      mass. Its long-term effect on the risk of osteoporotic fractures has yet to be
      proven. The authors conclude that prolonged tamoxifen treatment of postmenopausal
      women is associated with beneficial effects on serum lipid profiles and bone
      density; however, its effects on the morbidity and mortality from cardiovascular
      disease and osteoporosis and how it compares with the benefits of estrogen
      therapy remain to be determined by long-term comparative studies. TARGET
      AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES:
      After completion of this article, the reader will be able to be aware of the new
      indications for tamoxifen use prophylactically. To understand the various effects
      of tamoxifen on post-menopausal women and how they differ from the effects on
      premenopausal women.

PMID- 10198933
TI  - [The diagnostic report as an aid for determination of referral to inpatient
      rehabilitation].
AB  - The investigation analyzes some 206 standardized diagnostic reports submitted by
      office-practice physicians, demonstrating the role of diagnostic reports in
      determining access to medical rehabilitation. It is found that the practitioners
      added no further information about their patients' health status in half of the
      diagnostic reports given, and no further medical documents in one third. On the
      other hand, diagnostic reports that included details about the patients' ability
      to work as well as information about previous treatments resulted to a greater
      degree in direct award of a medical rehabilitation measure.

PMID- 10198934
TI  - [The quality of integration and care in workshops for the handicapped--The path
      to TQM in the workshops of the Gemeinschaftswerks fu"r Be- hinderte GmbH,
      Landstuhl].
AB  - Workshops for the Handicapped are exposed, as are other providers of social
      services, to powerful changes in social and economic conditions. Legal
      obligations (e.g. under the Federal Social Assistance Act BSHG), increasing
      customer demands and stronger competition make the ability to change a
      prerequisite, so that the quality and cost of providing services to the
      handicapped become a central theme. These changes in conditions have led the
      Gemeinschftswerk fur Behinderte GmbH, Landstuhl, to intensively consider the
      themes Quality and Total Quality Management (TQM). The efforts to introduce TQM
      were concentrated initially on the DIN EN ISO 9000 certification of the
      production processes in the workshops. Currently, the themes of Integration and
      Care were examined. After the central processes had been identified the
      performance descriptions of system, structure, process, result, and steering
      committee were extended by process diagrams and responsibility matrixes. This
      paper describes the path that workshops of the Gemeinschaftswerk fur Behinderte
      GmbH have taken towards TQM, with emphasis on presentation of the themes
      regarding quality of Integration and Care.

PMID- 10198935
TI  - [Falls incurred by the elderly resulting in injury: pathogenesis and
      rehabilitation].
AB  - Falls prove to be a significant problem in geriatrics. 5% of falls lead to
      fractures and 10% to soft tissue injuries. We examined retrospectively the
      rehabilitation course of 78 patients, who had been treated by us after falls
      leading to injury. Fractures of the neck of femur predominated with 57%, followed
      by other fractures of the lower limbs with 13%. The remainder of the falls with
      consequences of injury lead to fractures of other parts and soft tissue injuries.
      In 34% of the falls, the cause was estimated as predominantly intrinsic and in
      11% as extrinsic. 19% of the falls were a mixture of extrinsic and intrinsic
      factors. In 36% of the cases the cause remained unknown. Before the fall
      occurred, 72% were independent, 26% needed help and 1 patients was in need of
      care. After finishing rehabilitation 54% were independent, 34% needed help and
      11% were in need of care. 86% were able to return to their usual social
      surroundings. Rehabilitation after falls with consequences of injury goes beyond
      mere "orthopedic" treatment. To minimize the future risk of fall, a precise
      analysis of the cause of fall should be implemented. One should moreover try to
      optimize the environment to reduce the risk.

PMID- 10198936
TI  - [Introduction of the project "Westdeutsche Allgemeine Zeitung (WAZ) for visually
      impaired" (a talking electronic daily newspaper)].
AB  - In order to complete the range of topical media, that is currently available for
      the visually impaired, a working group is developing and testing the
      "Westdeutsche Allgemeine Tageszeitung (WAZ) for the visually impaired", an
      auditive electronic daily newspaper. The intention of this project is to take
      into consideration the needs of the visually impaired, especially of those who
      acquired the handicap in middle or later age and might feel that not being able
      to read the daily newspaper anymore reduces their quality of life to a great
      extent. The central aim therefore is to put the modern computer technology at the
      disposal of the impaired in a way that enables them to make use of the newspaper
      without having had previous experience. In a first phase of several months twelve
      probands in different personal settings will test a first prototype of the
      newspaper reading machine, a modified and optimated multimedia computer system
      with modern and speech output, at home. During this period the users will be
      intensively looked after and undergo psychodiagnostic examination. By means of
      analysing the data collected in extended talks and questionnaires concrete
      proposals on how to improve the machine are to be made and a statement about the
      potential impact of the electronic newspaper on the quality of life of the
      visually impaired--in the sense of a contribution to their rehabilitation--is to
      be given.

PMID- 10198937
TI  - [Concept formation and space perception in the blind--a summary of behavioral
      psychological studies].
AB  - Blindness entails an altered situation in the areas of information intake and
      processing concerning the aspects of perception, inter alia spatial, and concept
      formation. Numerous individual factors, such as life age, age at blindness onset,
      and occupational biography, constitute additional influences on the above
      cognitive faculties. A range of different study modules were used in seeking to
      obtain generally valid evidence relative to spatial perception and concept
      formation. The study overall had been directed at devising didactic and learning
      tools towards specific programme components. To illustrate potential applications
      of the study findings, the article briefly outlines a music programme guide
      intended for parents of blind, and possibly multi-handicapped, pre-school
      children.

PMID- 10198938
TI  - [The importance of the guide dog--does the guide dog still have a place in the
      next century?].
AB  - The guide dog is the sole living sensory aid recognized by Germany's statutory
      health insurance and medical rehabilitation system to help a blind person to
      compensate for the loss of eyesight. The guide dog is also the only recognized
      mobility aid that enables a blind person to reach destinations with greater speed
      and confidence by locating obstacles such as steps and ditches and avoiding them.
      Leading a person through traffic is not a dog's natural trait. Therefore,
      training and safety standards are essential to ensure smooth teamwork and
      communication between handler and dog. The guide dog offers much more than a
      simple technical aid such as a walking stick but not as much as a seeing human
      companion. To make up for this deficit, the blind person must also learn how to
      orientate him or herself and not just depend on the dog. For people blinded later
      in life a reliable guide dog can be an "aid with soul" that provides pet
      facilitated therapy and companionship. On the other hand, a guide dog with
      character disturbances, physical deficiencies or insufficient training can become
      an additional burden and social hindrance--even a danger for the person it is
      supposed to be protecting and others such as motorists. The puppy chosen to
      become a guide dog requires expert trainers and host families to rear and
      socialize it to interact appropriately with other dogs and other human beings.
      This stable upbringing is particularly important for the dog as it grows up and
      is confronted with negative influences. The blind person too learns to
      conceptualize the animal's own "dog world" so that he or she can build a firmer
      bond of trust.

PMID- 10198939
TI  - [BAR position paper on the future development of medical, vocational and social
      rehabilitation in the 14th Legislative Session. Federal Rehabilitation Council].

PMID- 10198940
TI  - [Vocational rehabilitation of mentally ill or mentally disabled persons from a
      functional perspective. Task Force 'Mental Disabilities', German Society for the
      Rehabilitation of the Disabled].

PMID- 10198941
TI  - Program evaluation of a sex education curriculum for women with mental
      retardation.
AB  - The effectiveness of a sexual education and health promotion program for 252
      women with mental retardation was analyzed using an evaluation model. We used
      confirmatory factor analysis (LISREL) to explain the pathways of learning and
      related the number of instructional contacts with the outcomes. Three factors
      (hygiene, social interaction, and sexual experience) affected sexual knowledge
      directly. An increase in sexual knowledge was directly associated with a greater
      number of instructional contacts. The analysis indicates that our program is
      effective and adds to our understanding of factors contributing to sexual
      knowledge for adults with mental retardation.

PMID- 10198942
TI  - A brief method for conducting a negative-reinforcement assessment.
AB  - A brief negative-reinforcement assessment was conducted with developmentally
      disabled children with severe destructive behavior. Five children were trained to
      engage in a simple escape response (e.g., a hand clap). Then each child was
      presented with a variety of stimuli or tasks that ranged on a scale from
      preferred to nonpreferred, based on parent ranking. The participant received a
      brief break from the stimuli or task, contingent on each escape response. For one
      child, an avoidance contingency was also implemented in which he could engage in
      the response to avoid the presentation of stimuli. Results showed that for each
      child, several stimuli were identified that may serve as effective negative
      reinforcers. Results also indicated that the procedure did not elicit any
      negative side effects for four children and low rates of destructive behavior for
      the fifth child. For one child, the results of the negative-reinforcement
      assessment were used to develop an effective treatment for destructive behavior.
      Additional applications of the reinforcement assessment to treatment
      interventions is discussed, as well as limitations to the procedure.

PMID- 10198943
TI  - Experimental functional analyses for challenging behavior: a study of validity
      and reliability.
AB  - The convergent validity of an experimental (analog) functional analysis was
      investigated by a comparison of three separate ways of interpreting the data
      derived from such an assessment: two previously published methods and the
      criterion Z method derived by the authors. Data from the experimental functional
      analysis of the challenging behavior(s) of 27 individuals with intellectual
      disabilities were analyzed to assess agreement between the three forms of
      interpretation. The test-retest reliability of all three methods over periods of
      2 weeks, 1 month, and 3 months was also calculated. The results suggest that the
      methods of interpreting function from experimental assessments can give different
      results and that the test-retest reliability of the experimental functional
      analyses is poor. The implications of these findings are discussed in relation to
      clinical practice.

PMID- 10198944
TI  - Longitudinal assessment of play and adaptive behavior in young children with
      developmental disabilities.
AB  - Deficits in appropriate play have been widely documented among children with
      developmental disabilities. However, there has been little research on the
      development of play or the relation between play and adaptive behavior in such
      children. The present study involved a longitudinal assessment of play and
      adaptive behavior among 13 preschool children with developmental disabilities.
      Children were assessed every 6 months over a 3-year period. Assessments included
      standardized ratings of adaptive behavior and videotape observations during
      unstructured free-play times in the preschool classroom. Adaptive behavior
      increased by almost one standard deviation from the first to the last round of
      data collection. Appropriate play was observed during approximately 20% of each
      30-min observation and showed little overall change over 3 years of study.
      Observed play was primarily functional (57%) and exploratory (28%) with less
      constructive (5%) and pretend (10%) play. Adaptive behavior scores were not
      consistently correlated with the amount or type of play. The results suggest
      little overall relation between appropriate play and other major domains of
      adaptive behavior. Implications for play-based assessment and intervention in
      early childhood special education are discussed.

PMID- 10198945
TI  - A validity study on the Questions About Behavioral Function (QABF) Scale:
      predicting treatment success for self-injury, aggression, and stereotypies.
AB  - We investigated the validity of the Questions About Behavioral Function (QABF), a
      checklist designed to assess antecedent behavior, using a sample of 398 persons
      with mental retardation and a targeted maladaptive behavior of self-injurious
      behavior, aggression, or stereotypies. The QABF was used successfully to derive
      clear behavioral functions for most individuals (84%) across all three target
      behaviors. Further, subjects with treatments developed from functional assessment
      (QABF results) improved significantly when compared to controls receiving
      standard treatments not based on functional analysis. Implications of the present
      findings for assessing and treating maladaptive behaviors are discussed.

PMID- 10198946
TI  - [Epidemiology of overweight in Switzerland: results of the Swiss National Health
      Survey 1992-93].
AB  - In many western countries more than half of the population is considered
      overweight (BMI > or = 25). METHODS: Data from the first national representative
      health survey for Switzerland (conducted 1992/93), including 7930 men and 7358
      women (response rate 71%) aged 15 and over, were used. Means and percentiles of
      body weight, body height and BMI were calculated for men and women of different
      age groups. Overweight was defined as a BMI > or = 25, graded as overweight grade
      I (25.00-29.99), grade II (30.00-39.99), and grade III (BMI > or = 40.00) and
      analyzed according to gender, age, etc. RESULTS: Mean values for height decreases
      with increasing age, and body weight increases up to the age of 55-64 years in
      men and women. BMI values of all percentiles and age groups are lower for women
      than for men with the exception of age groups of 55 years or older and the 90
      percentile. The prevalence of grade I overweight is 33.1% for men and 17.1% for
      women, of grade II overweight 5.8% and 4.5%, and of grade III overweight 0.3% and
      0.2% respectively. Overall prevalence of overweight is 21.8% for women and 39.2%
      for men. Increasing age is associated with a higher prevalence of overweight. The
      prevalence of overweight in men increases with age up to 55-64 years, then levels
      off. In women, prevalence continues to rise. Overweight is more common in men of
      all age groups than in women. CONCLUSIONS: Periodic studies of the national
      prevalence of overweight are essential for monitoring the magnitude, and changes
      in the magnitude, of this serious public health problem.

PMID- 10198947
TI  - [Angioedema induced by ACE inhibitors and angiotensin II-receptor antagonists:
      analysis of 98 cases].
AB  - Angiooedema has been reported as a rare but in most cases serious adverse effect
      of ACE inhibitors. Recent reports have indicated that angiotensin II-receptor
      antagonists may also induce angiooedema. As part of the spontaneous reporting
      scheme in Switzerland the Swiss Drug Monitoring Centre (SANZ) has received
      reports on 94 cases of ACE inhibitor-induced and 4 cases of angiotension II
      receptor antagonist-induced angiooedema. These 98 spontaneously reported cases
      were analysed in detail. 28 cases were classified as serious and in three
      patients intubation was even required. In 35% of cases angiooedema was induced
      within the first week of therapy and in 64% within the first year. In one case
      the angio-oedema displayed latency of 8 years. Latency of this duration shows
      that this adverse drug reaction (ADR) may be hard to detect. In 45 of the 98
      cases the oedema persisted for more than one day (maximum 2 months), although in
      some instances the patients continued ACE-inhibitor therapy. In 25 cases the
      oedema recurred, in one instance as many as 20 times. In rare cases angiooedema
      may also be induced by angiotensin II-receptor antagonists, although in such
      instances the course of the oedema was usually milder. In two of the four
      reported cases angiooedema recurred after switching from an ACE inhibitor to an
      angiotensin II-receptor antagonists. The four reported cases from Switzerland
      showed a similar profile when compared with 25 internationally documented cases.
      Our data indicate that angiooedema is a specific ACE inhibitor ADR. A protracted
      latency period may be observed and recurrence of oedema is frequent. Angiotensin
      II-receptor antagonist-induced angiooedema may also occur in rare instances.

PMID- 10198948
TI  - [External radiotherapy or non-steroidal anti-inflammatory drugs for prevention of
      heterotopic ossification following total hip replacement].
AB  - Heterotopic ossification (HO) is detained as the development of abnormal
      ossification in soft tissues. HO is a common disease after total hip replacement.
      Many therapeutic modalities have been proposed to prevent HO. The most commonly
      used modalities are non-steroidal anti-inflammatory drugs (NSAID) or ionizing
      radiation administered just before or immediately after total hip replacement. As
      far as external radiation therapy is concerned, there are several published
      randomized studies aimed at investigating its efficacy and timing related to
      surgery, and at comparing ionizing irradiation to NSAID. In this article we
      review the published data in order to define guidelines which could be used in
      daily practice for the choice of prophylactic treatment against HO.

PMID- 10198950
TI  - Endothoracic goiter with retro-tracheal and pre-esophageal migration.

PMID- 10198949
TI  - [Progressive muscular weakness due to subacute postinfectious polyradiculitis and
      myelitis].
AB  - In a 67-year-old patient, generalised stable muscular weakness preexisting for
      several years became rapidly progressive within a few weeks prior to
      hospitalisation. He died one month after admission from acute cardiocirculatory
      failure. There was no history of muscular pain, clinical examination showed weak
      or absent tendon reflexes, hyposensibility of the dorsa of his feet,
      fasciculations and myocloni of the muscles of the lower limbs as well as a
      generalised muscular atrophy. Polyneuropathy due to diabetes mellitus and
      monoclonal IGG-kappa-type gammopathy were preexisting. CSF examination showed
      inflammatory cerebral fluid changes and further investigations revealed
      inflammatory polyradiculopathy affecting mainly motor nerve fibres. There was
      evidence of a reactivated varicella-zoster infection in serum and in the
      cerebrospinal fluid samples. The search for a tumour, vasculitis or a drug
      related cause for this syndrome remained negative. Neuropathological examination
      at autopsy showed subacute polyradiculitis accompanied by myelitis. The most
      probable cause of this disorder is immune-mediated polyradiculitis after
      varicella-zoster infection.

PMID- 10198951
TI  - The Swiss Network of Dermatology Policlinics HIV prevalence study: rationale,
      characteristics and results (1990-1996).
AB  - The Swiss Network of Dermatology Policlinics (SNDP) has monitored the prevalence
      of HIV among patients treated for a sexually transmitted disease (STD) since
      January 1990. A questionnaire was sent to each policlinic in the network (Basel,
      Bern, Geneva, Lausanne, and two in Zurich) to collect information on their
      participation in this study and the characteristics of the network. The responses
      reveal that the six policlinics followed the HIV prevalence study protocol in a
      uniform manner and had similar logistical and organisational characteristics HIV
      prevalences in this population were high (1.6% among heterosexuals, 24.0% among
      male homo/bisexuals, and 35.7% among injecting drug users), have remained stable,
      and vary considerably by policlinic. In conclusion, we found that the policlinics
      have correctly implemented the HIV prevalence study and that the SNDP is a
      homogeneous sentinel surveillance system. Knowledge of the organisation and
      characteristics of the SNDP has allowed us to better interpret and present our
      data, and we recommend that other sentinel surveillance systems of this type
      collect this sort of information.

PMID- 10198952
TI  - Influence of patient's dressing on spontaneous physical activity and length of
      hospital stay in surgical patients.
AB  - Wearing hospital gown (HG) as opposed to plain-clothes (PC) may contribute to the
      general state of inactivity of hospitalised patients. We designed a randomized
      study to determine the influence of clothing on the level of spontaneous physical
      activity (SPA) and to assess the length of hospital stay. Using triaxial
      accelerometry we measured the SPA in two groups of surgical patients, before and
      after an elective operation. Twenty eight patients received instructions to wear
      plain-clothes (group PC) during their stay in the hospital as soon as possible
      from a surgical point of view. Twenty-nine patients, serving as a control group,
      did not receive any specific instructions and as a result, were mostly wearing
      hospital gowns (group HG). Following the admission to the hospital, both groups
      showed a 50% decrease in SPA when compared to the recordings obtained during the
      last 24 hours spent at home. During the postoperative period, the SPA increased
      progressively in both groups. Although patients in group PC tended to be more
      active than those in the control group, the SPA was not significantly different
      (P = 0.4). Similarly, patients in group PC left the hospital 10 hours earlier
      than patients in group HG (P = 0.4). The power of our study was nevertheless low
      and a sample size of 700 patients might show statistically significant results.
      We conclude that wearing plain-clothes when hospitalized for elective surgery is
      not associated with complications and could be included in postoperative
      rehabilitation program.

PMID- 10198953
TI  - [Smoking cessation in pharmacies--evaluation of the smoking cessation campaign
      "Tobacco adieu!" among pharmacists in Basel].
AB  - Now as in the past, tobacco consumption is a major health problem in Switzerland.
      Efforts to reduce tobacco consumption include different preventive strategies.
      Although dispensary pharmacists have increased their efforts in health promotion
      and prevention in recent years, their role in tobacco prevention has not been
      documented so far. The "Tobacco Adieu!" campaign to support smoking cessation was
      introduced in pharmacies as a low threshold offer in Basle in 1996. This paper
      assesses the process and the effect of this effort. Participating pharmacies were
      interviewed during the evaluation and all consultations in this area were
      recorded in questionnaires. Customers requesting counselling from pharmacies
      during the campaign were also asked to fill in a questionnaire regarding their
      smoking behaviour and their experiences in the pharmacy. The offer was well
      accepted by the public: During the four week period, about 2,000 client contacts
      for smoking cessation took place in the 63 participating pharmacies. Compared to
      the pre-campaign situation, more intensive counselling took place. Clients who
      received counselling in the pharmacies generally attested to its good quality. In
      addition to counselling, further care during the smoking cessation phase was
      offered to clients who wanted to quit smoking. Follow-up visits were agreed in 76
      percent of the cases. The project shows that smokers can be motivated to consider
      cessation and supported in the process by pharmacists. Therefore, pharmacies can
      be used as a low threshold offer in this context. Expansion of this programme in
      public pharmacies seems justified. However, continuing education and a motivated
      team are the prerequisites for successful counselling of smokers in pharmacies.

PMID- 10198954
TI  - [Use of unconventional therapies by cancer patients].
AB  - Unconventional therapies are increasingly accepted and used by professionals and
      lay persons. In this study, we analyzed correlations between sociodemographic
      variables of cancer patients, their disease and use of unconventional therapies.
      In an oncological out-patient department we collected the data relevant for the
      study objectives by means of a questionnaire. The sample comprised of 154
      persons. The younger age group, married individuals and those in mid level
      occupational positions had more experience with unconventional therapies. The
      strongest predictors for usage were "age", length of illness" and "being able to
      go to work or to do house work". Doctors should be familiar with these methods in
      order to support their oncologic patients. As unconventional therapies will be
      used more often research should be intensified.

PMID- 10198955
TI  - [Recording of multiple sclerosis in Swiss cause of death statistics. A 10-year
      mortality follow-up of the Bern prevalence study].
AB  - Based on data from a multiple sclerosis (MS) prevalence study which had been
      carried out in 1986 in the canton of Berne, Switzerland, a follow-up was
      performed 10 years later to gather information on mortality in the original study
      population. The authors used information on residency and death as gathered from
      municipal offices and, additionally, by record-linkage with the Swiss cause of
      death statistics. Slightly more than 80% of the cases were identified
      unequivocally as of January 1996. Among them, 21% of the cases died during the
      ten-year period; 70% of them have an MS entry in the cause of death statistics,
      mostly as the main cause of death. A large proportion of the non-identifiable
      cases appear to be related to mortality; thus, the findings here do not provide a
      promising basis for certain further analyses. In conclusion, continuous updating
      of personal data is the only way to avoid loss to follow-up in the carefully
      assembled prevalence database.

PMID- 10198956
TI  - [Correction of micronutrient deficiency--the most important aspect of healthy
      nutrition conception for the Russian population].

PMID- 10198957
TI  - [Effect of biologically active food additives on energy metabolism and human body
      weight].
AB  - Review is devoted to analysis of human energy requirements depending on age, sex,
      occupational and living condition. Special attention was paid to importance of
      strict balance in organism between consumption and expense of energy. Modern
      views on mechanism of action food supplements as additional instrument of
      regulation of energy metabolism for correction of surplus body weight is given.
      Review is the first attempt of systematisation of biologically active food
      supplements according to their mechanism of action both on nutrition processes
      and on biochemical mechanisms of assimilation and utilisation of macronutrients,
      in particular of fats and carbohydrates.

PMID- 10198958
TI  - [Effect of biologically active food additives containing autolysate of baker's
      yeast and spirulina on intestinal permeability in an experiment].
AB  - Influence of bioactive food supplements (BFA) intake on intestinal barrier
      permeability to macromolecules of polyethylene glycol 4000 was studied in rats
      with intestinal anaphylaxis and after external gamma-irradiation. BFA studied
      included autolysed baker's yeast ("Vitasil") and edible algae Spirulina
      platensis. Intake of complex additive Vitasil + Spirulina resulted in significant
      diminution of permeability before irradiation and its partial normalization (24%
      decrease) after irradiation. Spirulina additive intake led to practically
      complete normalization of permeability (1.84 times decrease) in anaphylactic
      rats. It is concluded that Spirulina and Vitasil are promising BFA for organism
      general resistance elevation.

PMID- 10198959
TI  - [Investigation of the safety of the product "Rialam."].
AB  - The data on safety investigation of product "Rialam", which is proposed as
      biologically active food supplement are presented. Chronic experiment and single
      generation experiment were made on Wistar rats. It is shown that diet "Rialam" in
      dose 100 mg/kg of body weight didn't influence negatively on growth and
      development of rats blood parameters, immune status, internal organs morphology,
      metabolism, hadn't embryotoxic, gonadotoxic and teratogenic action.

PMID- 10198960
TI  - [Optimization of a method of solid-phase immunoenzyme analysis for determination
      of chloramphenicol in milk].
AB  - The method of solid-phase enzyme linked immunosorbent assay (ELISA) for
      quantitative detection of chloramphenicol (CAP) in milk was developed.
      Peculiarities of the adsorption on the microtitre plates surface of CAP-ovalbumin
      conjugate were investigated. Different conditions of competition stage of the
      analysis were studied. Conditions providing CAP monitoring in human blood serum
      in the clinical range were optimized. Matrix effect on the assay results was
      studied. The specificity of the analytical system was investigated and the
      reagents stability was examined. The method developed permits CAP concentration
      to be determined in human blood serum, diluted 1/100, in the linear range from
      0.1 to 100 ng/ml. The assay is characterized by high sensitivity (0.08 ng/ml) and
      good reproducibility (CV < 10.8%), assay time is about 3 hours. The correlation
      coefficient with HPLC is 0.977.

PMID- 10198961
TI  - [Enterosorption by nonstarch polysaccharides as a method of treatment of children
      with mercury poisoning].
AB  - Possibility of apple pectin "Classic AU-701" (E-440) usage as the means of
      detoxication was evaluated in 146 children of 7-14 years old with the increased
      content of mercury in urine. Under the influence of enterosorption the mercury
      withdrawal with urine increased, the period of mercury intoxication was shortened
      by 6 weeks, the hemogram and vegetative regulation indices of the affected
      children improved. The authors consider pectin to be effective in mercury
      intoxication treatment. It may be also used to increase intoxication resistance
      under exposure to chemicals.

PMID- 10198962
TI  - [Role of polyunsaturated fatty acids in diet therapy of children with allergic
      diseases].
AB  - 135 pediatric patients receiving hypoallergic diet were included into the study
      group. The control group consisted of 20 children. The impact of PUFA omega-3
      biologically active supplements (polyen, prima-Oil) was studied in hypoallergic
      rations. Biochemical indices were simultaneously investigated. The revealed
      dynamic changes of fatty acid spectrum in plasma and red cell membranes, cellular
      and humoral immunity status and eicosanoids synthesis were followed by positive
      clinical changes. Diets enriched with biologically active supplementation (PUPA
      omega-3) can be recommended for application in pediatric practice.

PMID- 10198963
TI  - [Dynamics of the natural antibody level as affected by the biologically active
      food supplement "Vitol" in patients with hypertensive disease and obesity].
AB  - The dynamics of level of natural antibodies to catecholamines (adrenaline,
      noradrenaline and dopamine) and factors of blood coagulation system (thrombin,
      antithrombin III and alpha 2-macroglobulin) in 122 patients with hypertension and
      obesity was studied in hyposodium antiatherosclerotic diet and this diet enriched
      with phospholipid preparation "Vitol" during 4 weeks. Universal normalizing
      effect of the diet consists in increase of levels of natural antibodies to
      adrenaline, noradrenaline, dopamine, thrombin, antithrombin III and alpha 2
      macroglobulin was found. The influence of the diet was more expressed during it
      enrichment by "Vitol".

PMID- 10198964
TI  - [Effect of fructose-containing beverages on glycemic parameters in patients with
      type II diabetes mellitus].
AB  - The dynamics of glycemia after meal in 21 patients with type II diabetes under
      the influence of drinks with fructose or sugar and enriched with soluble fibres
      was investigated. To estimate glycemia after meal in first stage of investigation
      the test-meals with 50 g carbohydrates (cocktails of juices "Multivitamin" with
      fructose and sugar, or bread) were used. In second stage, carbohydrates "Peach
      nectar with fructose" and cocktail of juices "Multivitamin with fructose" were
      used. The level of glucose in capillary blood was defined after 14-h fasting and
      30, 60, 120 and 180 minutes after every test-meal. "Peach nectar with fructose"
      enriched with fructose and soluble food fibres (pectin) caused glycemic response
      in a less degree.

PMID- 10198965
TI  - [Medical aspect of food starch].
AB  - In the review are considered aspects of food starch such as its relationship with
      cancer of the large intestine, its absorption, digestion and metabolism,
      influence of starch on the composition and biochemical characteristics of
      microbiocenosis.

PMID- 10198966
TI  - [Significance of CD-ROM in medicine].
AB  - The article evaluates some multimedia programs offer for computers for medicine
      information, teaching and learning. Information technology has the potential to
      revolutionize the way medicine is learned by students and practitioners. Medicine
      with its abundance of facts and richness of imaging techniques has always been
      adopting new technologies to improve teaching and training. As a natural
      consequence, the use of computer-based multimedia technology is generally
      increasing in medicine. Especially the use of interactive multimedia technology
      seems promising to improve training and education and increase accessability of
      highly specific material. It can combine the best of the text-book and the video,
      but above all the use of interaction should produce untold benefits.

PMID- 10198967
TI  - [What is the attitude of Mrs. and Mr. Austria regarding their health system?].
AB  - 1451 questionnaires were used in a survey. With 87% the population showed great
      interest for health questions. 2 thirds satisfaction with the present health
      system combined with 1 third of pessimism, concerning the opinion that the health
      system in the present form cannot persist because of financial difficulties.
      Higher educational levels showed more critisism. 800 verbal statements demanded
      more time for medical conversation; more esthetics in hospitals; inclusion of
      dental and spectacle-supplies into the health system; more alternative medicine
      (with very different opinions what should be ment by it). Selection of special
      risk group, like smoking, adipositas and extreme-sports. Cures were charged very
      differently, from "regular cheating" to an importance of getting allocation for
      the cure more easily. In 3 panel discussions confirmation of the above-mentioned
      items and some additional new points could be obtained including the importance
      of rehabilitation in old age.

PMID- 10198969
TI  - [Smoking, cardiovascular diseases and possibilities for treating nicotine
      dependence].
AB  - Diseases of the cardiovascular system such as coronary heart disease,
      hypertesion, peripheral occlusive arterial disease, and their final or lethal
      states (acute myocardial infarction, apoplectic stroke, congestive heart failure)
      occur 3 to 4 times more frequently than lung cancer in heavy smokers. Cigarette
      smoking impairs the courses of the microcirculation by an elevated viscosity of
      the blood or plasma, by a diminished deformability of the red blood cells, by
      elevated white cell counts, by activation of several blood clotting factors such
      as factor XIII and von Willebrand factor, by an elevated aggregability of the
      blood platelets, and by an increased uptake of fibrinogen into the endothelium of
      the blood vessels. After cessation of smoking these effects are widely normalized
      even though nicotine is still administered. Proposals for the cessation of
      smoking and for the use of nicotine replacement (patch, chewing gum, etc.) were
      offered because the inhaled tobacco smoke mainly damages health while the smokers
      are addicted only by nicotine. A less restrictive distribution of nicotine
      preparations for replacement therapy should enable the heavy smoker in his first
      phase of smoking cessation to combine the nicotine administration with reduced
      cigarette smoking. Each decrease in the carbon monoxide content of the expired
      air with subsequent decrease in the carboxyhemoglobin content of the blood
      possibly diminishes the risk of cardiovascular events. This way of treatment
      gives new opportunities for the treatment of the smoking patient for every
      physician.

PMID- 10198968
TI  - [Effect if 6-week nutritional intervention with enzymatic yeast cells and
      antioxidants on exercise stress and antioxidant status].
AB  - The aim of the present study was to investigate the influence of a yeast cell
      preparation rich in antioxidant vitamins, antioxidant enzymes, trace elements and
      minerals on the exercise-induced stress reaction and antioxidant status. The
      study was carried out in a non-blinded, controlled design. After a 6 week pre
      ingestion period, 9 highly endurance-trained athletes took the preparation twice
      daily for another 6 weeks. After each phase venous blood samples were drawn in
      the resting state after an overnight fast followed by a strenuous 15 km cross
      country race. 1 h after the exercise venous blood sampling was repeated. Compared
      to the pre-ingestion period, the following significant alterations could be
      detected after 6 weeks of ingestion: 1) In the resting state, soluble interleukin
      2 receptor (p < 0.05) and plasma fibrinogen (p < 0.01) were shown to be lower
      whereas plasma fibronectin was increased (p < 0.01). 2) 1 h after the race the
      significant difference in fibrinogen and fibronectin was confirmed. In addition
      myoglobin (p < 0.01) and CKMM3 (p < 0.05) as well as mangan superoxid dismutase
      (p < 0.05) were reduced. In conclusion, the 6-week ingestion-period resulted in
      an improvement of the systemic and muscular stress reaction. In addition, the
      decrease in mangan superoxide dismutase concentration can be interpreted as a
      sign of reduced free radical stress. However, these preliminary results have to
      be confirmed in larger trials in blinded designs. In addition, there seems to be
      a rationale for testing the effects of yeast-cell preparations in patients with
      chronic degenerative diseases as some of the investigated parameters are involved
      in the pathophysiology of such illnesses.

PMID- 10198970
TI  - [Quality management in oncology].

PMID- 10198971
TI  - [Quality management in oncology].
AB  - Quality management (QM) is the intention to achieve an achievable quality of
      care. QM means collecting, comparing and analysing data, a prerequisite for
      quality to be translated into quantifiable outcome indicators. In the field of
      oncology with chronic courses of the disease, longterm results are hard to obtain
      due to the open channels of cancer care. Longterm results would, however, be
      required in order to allow comparisons between different physicians and
      hospitals. If differences do occur, the cause(s) of variation could be
      identified. How much competition is "healthy" for health (cancer) care? In order
      to implement QM programs, longterm personal commitment of everybody involved
      (medical staff and administration) is required. However, it has to be questioned
      whether all those involved are also prepared. Is the American system of "managed
      care" the solution to an improved care quality?

PMID- 10198972
TI  - [Development of standards and guidelines by the German Cancer Society].
AB  - Since 1993, the German Cancer Society is working on interdisciplinary standards
      and short guidelines for diagnosis and treatment of malignant diseases. They are
      developed by interdisciplinary groups of experts and by coordination with the
      involved medical scientific societies and several coopted partners, in particular
      the Scientific Advisory Board of Deutsche Krebshilfe and the Working Group of
      German Cancer Centers. Standard operating procedures for the development and
      continuous actualization and improvement are observed. Standards and guidelines
      are published in the book series "Quality Assurance in Oncology", in several
      medical journals and electronically in the world wide web.

PMID- 10198973
TI  - [Evaluation of guidelines in oncology].
AB  - Several activities regarding guidelines have been developed in Germany within a
      short time. It is desirable especially in the field of oncology that procedures
      are stated as proven effective, proven ineffective, and possibly effective by
      using procedures of evidence based medicine. However, the low impact of
      guidelines on the medical practice has to be taken into account. The kind of
      errors of known deviations should decrease the expectations. This altogether
      should motivate for a closer look what really happens in the daily routine. It
      should also reflect the hospital's and physician's outcome and might provide
      hints to medical standards. Improving the still insufficient documentation, which
      may describe quality of care, can provide important features. This has to be
      remembered when undertaking activities regarding guidelines.

PMID- 10198974
TI  - [Regional implementation of guidelines as a lesson for cancer centers].
AB  - 43 German Comprehensive Cancer Centers (CCC) are gathered together in a
      cooperative group (Arbeitsgemeinschaft Deutscher Tumorzentren e.V. = ADT). The
      main task of these centers is the development of interdisciplinary structures
      which ensure provision of the optimum facilities of diagnostic procedures,
      treatment modalities and follow-up management for every patient in all regions of
      Germany. To realize these efforts, the CCC have to establish expert groups
      dealing with definite tumor entities and establishing guidelines, which have to
      be propagated in the respective regions. The experts are responsible for the
      spreading of relevant information which has to be actualized periodically. The
      basis of this information system can be the guidelines which are developed
      together with the German Cancer Society (Deutsche Krebsgesellschaft e.V. = DKG).
      However, in some cases, the CCC have a longstanding tradition with the
      elaboration and use of their own guidelines. Yet, these regional guidelines
      should be in very close congruency with the overlaying national guidelines.
      Deviations from these general rules have to be explained by the citation of
      reliable literature from peer reviewed journals. All guidelines must be worked
      out sticking to the rules of "Evidence Based Medicine" (EBM). An inquiry launched
      by the ADT revealed different needs in several CCC for further establishment of
      interdisciplinary expert panels and guidelines.

PMID- 10198975
TI  - [Continuing medical education--a necessity, with or without proof?].
AB  - The proof of continuing medical education (CME) ist necessary. Until now,
      physicians have the chance to solve this problem by themselves and to participate
      voluntarily at certification and evaluation of CME and to document their efforts
      to the benefit of the patients. The experiences, which medical societies will
      gain by undertaking projects to proof CME, will show ways for a common system of
      certification in Germany being compatible in whole Europe.

PMID- 10198976
TI  - [Health technology assessment in the international context: where does Germany
      stand? For the "German Scientific Working Group Technology Assessment for Health
      care"].
AB  - The evaluation of medical technologies, Health Technology Assessment (HTA), is
      gaining more and more importance in Germany. Starting from a comprehensive
      definition of the term medical technology, this article first describes the
      development of HTA since the seventies as an instrument for improving decision
      making in health policy. HTA is presented as a repetitive cycle of a sequence of
      steps starting with the prioritization of topics to be evaluated to the analysis
      of the impact of the results. Current trends in the further improvement of HTA
      methods are described, such as the formalization of the topic selection. The
      current situation in Germany is presented with regard to the regulation of
      licensing/market entry, coverage by the statutory health insurance, and the
      utilization of medical technologies. Finally, current activities in the field of
      HTA in Germany as well as the role of the German Scientific Working Group
      Technology Assessment for Health Care are discussed.

PMID- 10198977
TI  - [An online information system "LEITLINIEN-IN-FO"--a contribution to quality
      management in health care].
AB  - An online-information service contianing clinical practice guidelines
      ("LEITLINIEN-INFO"--available via) based on similar programs from Scotland and
      Canada--was developed by the German Guidelines Clearinghouse (Agency for Quality
      in Medicine, Cologne). The service focuses on continuing medical education
      regarding guideline methodology and tools for critical appraisal of guidelines.
      It contains guideline appraisal reports developed in cooperation with the German
      Cochrane-Center. Special importance is given to a hyperlink collection of German
      and international guideline-data-bases. Backgrounds, aims, and structures of the
      information program are discussed.

PMID- 10198978
TI  - [Treatment guidelines--chronic heart failure. Recommendations for therapy of
      chronic heart failure of the Medical Commission of the German Medical Branch].

PMID- 10198980
TI  - [Risk management as a means of quality assurance in the hospital].
AB  - Each modern organized hospital needs an effective risk-management. This does not
      only mean to avoid incidents to reduce insurance costs to a low level. Reduced on
      this aspect, the hospital management will not be able to reach a broad acceptance
      for the tasks of risk-management. Each physician naturally avoids incidents in
      daily hospital routine by following good medical practice in medical treatment.
      At the same time positive statistics will guide to an optimized high valued
      treatment quality. At first, critical situations have to be managed when they
      occur. A critical situation is very often forgotten after successful management
      and quality deficits stay as they are. Knowledge from the daily hospital routine
      are not used, procedures are not improved. There is no system of perpetous
      monitoring installed. Risk-management will guide to a process of continuous
      quality improvement in high risk departments, where processes and structures are
      not as good as they could be. In addition to measurements forseen by law, risk
      management means constant evaluation of the quality of the own hospital
      treatment. Risk-management is not only extern quality assurance but also a intern
      program. It opens a wide field for self responsible measurements and own
      creativity in practical implementation.

PMID- 10198979
TI  - [Quality criteria for cost-benefit analysis in oncologic nuclear medicine and
      state of its realization].
AB  - Additional or expensive diagnostic imaging had to prove prospectively their
      diagnostic efficacy, their therapeutic efficacy, or their patient-outcome
      efficacy. The adherence to methodologic standards in the cost-effectiveness
      literature is required. Based on the bone scintigraphy in oncologic patients with
      a low prevalence of bone metastases, the cost-effectiveness is questionable. The
      economic role of 99m-Tc MIBI mammoscintigraphy and of the imaging for carcinomas
      of unknown origin is discussed controversially. Based on the reimbursement of the
      positron emission tomography (PET) in the USA and in Switzerland, cost
      effectiveness literature and decision trees for cost-utility analyses are
      reviewed. PET imaging was cost-effective in non-small-cell lung cancer, in
      solitary pulmonary nodules, in recurrent colorectal cancer, in metastatic
      melanoma and in recurrent head and neck cancer with reduced costs of management.
      The German health insurance calls for PET-data based on the national
      reimbursement.

PMID- 10198981
TI  - [Medical guidelines--further development or a falling off? Account of a meeting
      organized by the University of Bremen].

PMID- 10198982
TI  - [Christian Georg Schmorl].

PMID- 10198983
TI  - [To the Christian-Georg-Schmorl-memorial lecture: 50 years of lupus erythemotosus
      cells].

PMID- 10198984
TI  - [50 years of LE cells--inception of autoimmune diagnostics. Christian Georg
      Schmorl memorial lecture].

PMID- 10198985
TI  - [Effect of diclofenac on human osteoblasts and their stromal precursors in vitro
      in relation to arthroplasty].
AB  - INTRODUCTION: Results of animal experiments have demonstrated that the osseous
      integration of non-cemented prostheses can, at the very least temporarily, be
      impaired by the application of non-steroidal antiphlogistic agents (such as
      diclofenac). It is the objective of this study to examine whether there is a
      direct influence of diclofenac used in usual clinical dosages (3 times 50 mg
      daily) on bone cells and their progenitor cells which would explain the observed
      slow integration of the prostheses. METHODS: To investigate this, cultivated
      human in vitro osteoblasts and stromal bone marrow cells were incubated with
      increasing doses of the medications. Our study focused on the effect of
      diclofenac application on proliferation and functional metabolism in both cell
      lines. The measurable maximal plasma concentration 2 h after the application of
      one tablet Voltaren 50 reached 1.6 micrograms/ml. This correlated with diclofenac
      concentrations between 1 and 10 ml found in our experiments. The detected values
      were correlated to the control group (0 microgram/ml diclofenac). RESULTS: The
      drug effect upon osteoblasts was higher than on progenitor cells. The
      proliferation of in vitro stromal bone marrow cells, compared to untreated cells,
      was found to be decreased. We observed a decrease to 82% at a diclofenac
      concentration of 1 microgram/ml, Osteoblasts exhibited a decrease to 97.5% at the
      same concentration. The DNA synthesis increased to 118% in stromal bone marrow
      cells, in osteoblasts to 144%. In contrast, we detected a neglectible decrease to
      92% in the collagen synthesis of osteoblasts compared to untreated cells. The
      synthesis of osteocalcin by osteoblasts increased to 119%. The alkaline
      phosphatase activity was found to be decreased to 88% in stromal bone marrow
      cells and increased in osteoblasts to 111%. CONCLUSION: Temporary inhibiting
      effects on osseous integration in non-cemented prosthesis by diclofenac could be
      caused by a disturbance in the anabolic bone metabolism, exhibited by an increase
      of osteoblastic osteocalcin expression. Osteocalcin as a known negative regulator
      of the osteoneogenesis is most likely inhibiting the collagen matrix deposition.

PMID- 10198986
TI  - [Age at disease onset and delayed diagnosis of spondyloarthropathies].
AB  - A questionnaire with 78 questions concerning the situation of ankylosing
      spondylitis (AS) sufferers in Germany was distributed to a representative 3000
      out of the more than 14,000 patient members of the German AS society; 1614
      patients (54%) responded. The age distribution of these patients roughly agrees
      with that expected due to the distribution of the age at diagnosis and the age
      distribution of the German population. The group of patients more than 65 years
      old is, however, under-represented. It turned out that at least 28% of the
      patients responding do not suffer from idiopathic AS but from other
      spondyloarthritides (spondylitic psoriasis, spondyloarthritis combined with
      Crohn's disease or ulcerative colitis). The distribution of the age at disease
      onset agrees well with that published in 1984 by van der Linden et al.: For 4% of
      the patients, the age at appearance of the first spondylitic symptoms was less
      than 15 years, for 90% it was 15-40 years and for the remaining 6% more than 40
      years. The average age at disease onset was 25.6 years. The spondyloarthritides
      do not differ significantly in the distribution of the age at the first
      spondylitic symptoms. The distribution of the age at diagnosis did not differ
      significantly between male and female patients, in contrast to the findings by
      van der Linden et al. in 1984. The average age at diagnosis was 34.3 and 35.3
      years for male and female patients, respectively. The resulting mean diagnosis
      delay for male and female patients was 8.4 and 9.8 years, respectively. Whereas
      the average diagnosis delay was still 15 years for patients with disease onset in
      the 1950s, it was only 71/2 years for patients with disease onset in 1975-79. It
      is not yet possible to predict if an average diagnosis delay less than 71/2 years
      results for patients with a disease onset later than 1980, because the number of
      further diagnoses to be expected for patients with disease onset in these years
      is not negligible. Twenty-six percent of the patients (22% of the males, 34% of
      the females) have relatives, likewise, suffering from AS. Whereas patients with
      familiar AS experience their first spondylitic symptoms, in the average, 11/2
      years earlier than patients without relatives suffering from AS, the difference
      is 5 years for patients suffering from spondyloarthritis combined with ulcerative
      colitis. Reports written for patients on other results of the survey can be found
      in the newsletter "Bechterew-Brief" of the Deutsche Vereinigung Morbus Bechterew.

PMID- 10198987
TI  - [Pneumococcal septicemia in functional asplenia: first manifestation of systemic
      autoimmune disease?].
AB  - A 35 year old female was admitted into the hospital because of rapid onset fever
      and chills. Streptococcus pneumoniae could be isolated from blood as the
      responsible pathogen for septicemia. Necroses of fingers and feet occurred. The
      clinical signs of an overwhelming post-splenectomy infection (OPSI) were evident.
      High-dose penicillin was administered and the patient recovered. Howell-Jolly
      bodies were seen in peripheral blood smears. A spleen within normal size could be
      demonstrated in CT and sonography. Angiologic findings showed intact splenic
      arteries and a normal vein, whereas the small splenic vessels were rare. MRT of
      the spleen using Endorem (Fe), showed only a minimal uptake of the RES. In a
      scintigram of spleen and liver using 320 MBq Tc-99m nanokoll, the spleen was not
      visible. Thus, functional asplenia was demonstrated by Howell-Jolly-Bodies and by
      image methods. An increased antinuclear antibody level and a Sm-antibody lead to
      the diagnosis of undifferentiated connective tissue disease. As far as we know
      this is the first case that functional asplenia was the first symptom of a
      systemic autoimmune disease.

PMID- 10198988
TI  - [RS3PE-syndrome].
AB  - The RS3PE syndrome (Remitting Seronegative Symmetrical Synovitis with Pitting
      Edema) is a manifestation of rheumatoid arthritis in the elderly with a good
      prognosis. It usually presents as an acute, symmetric polysynovitis with edema of
      the dorsum of the hands and feet. Anti-inflammatory treatment with
      corticosteroids leads to prompt improvement. We describe the case of an 81 year
      old man with a primarily unilateral manifestation involving the right hand. A
      thrombosis of the axillary vein was suspected. Within a few days he developed a
      pitting edema of the dorsum of the other hand. Movement of both shoulders and
      wrists was painful. Low-dose corticosteroid therapy resulted in a rapid
      improvement of the edema and the inflammatory symptoms.

PMID- 10198989
TI  - [Prof. Dr. med. habil. Gerhard Heidelmann, 80 years old].

PMID- 10198990
TI  - [New mechanism of insulin signal transduction: participation of the adenylate
      cyclase signal system in growth stimulating insulin effect].

PMID- 10198991
TI  - [The new method of detection of the internal mirror symmetry in amino acid
      sequences of the regulatory subunits of phosphatidylinositol-3-kinases and
      relation between symmetry and primary structure conservation].

PMID- 10198992
TI  - [Effect of cold adaptation on ganglioside level in the rat brain subcellular
      fractions and their fatty acid composition].

PMID- 10198993
TI  - [Conformation-functional relations in oligomethylenesulfone organophosphorus
      inhibitors of cholinesterases of various origin].

PMID- 10198994
TI  - [Digestive enzyme activity in the small and large intestines, liver, and kidney
      in rats with low and high excitability threshold before and after pain-induced
      emotional stress].

PMID- 10198995
TI  - [Circadian rhythm of various melatonin biosynthesis parameters in the silver fox
      Vulpes fulvus during domestication].

PMID- 10198996
TI  - [Various ecological and physiological aspects of feeding and growth of the Baikal
      seal Pusa sibirica pups].

PMID- 10198997
TI  - [Functional characteristics of the binocular sector neurones of the squirrel
      Sciurus vulgaris striate cortex].

PMID- 10198998
TI  - [Possible stereochemical relations between oligonucleotides and
      aminoacyladenylates as a basis for genetic code origin (a hypothesis)].

PMID- 10198999
TI  - [Effects of MgATP on Cl(-)-activated Mg-ATPase from animal nervous tissue].

PMID- 10199000
TI  - [Spectral composition of the spontaneous contractile activity various parts of
      the rat offspring gastrointestinal system: a study in vitro and in vivo].

PMID- 10199001
TI  - Segmentation of confocal microscope images of cell nuclei in thick tissue
      sections.
AB  - Segmentation of intact cell nuclei from three-dimensional (3D) images of thick
      tissue sections is an important basic capability necessary for many biological
      research studies. However, segmentation is often difficult because of the tight
      clustering of nuclei in many specimen types. We present a 3D segmentation
      approach that combines the recognition capabilities of the human visual system
      with the efficiency of automatic image analysis algorithms. The approach first
      uses automatic algorithms to separate the 3D image into regions of fluorescence
      stained nuclei and unstained background. This includes a novel step, based on the
      Hough transform and an automatic focusing algorithm to estimate the size of
      nuclei. Then, using an interactive display, each nuclear region is shown to the
      analyst, who classifies it as either an individual nucleus, a cluster of multiple
      nuclei, partial nucleus or debris. Next, automatic image analysis based on
      morphological reconstruction and the watershed algorithm divides clusters into
      smaller objects, which are reclassified by the analyst. Once no more clusters
      remain, the analyst indicates which partial nuclei should be joined to form
      complete nuclei. The approach was assessed by calculating the fraction of
      correctly segmented nuclei for a variety of tissue types: Caenorhabditis elegans
      embryos (839 correct out of a total of 848), normal human skin (343/362), benign
      human breast tissue (492/525), a human breast cancer cell line grown as a
      xenograft in mice (425/479) and invasive human breast carcinoma (260/335).
      Furthermore, due to the analyst's involvement in the segmentation process, it is
      always known which nuclei in a population are correctly segmented and which not,
      assuming that the analyst's visual judgement is correct.

PMID- 10199002
TI  - Four-dimensional factor analysis of confocal image sequences (4D-FAMIS) to detect
      and characterize low copy numbers of human papillomavirus DNA by FISH in HeLa and
      SiHa cells.
AB  - Visualization and localization of specific DNA sequences were performed by
      fluorescence in situ hybridization, confocal laser scanning microscopy (CLSM),
      and four-dimensional factor analysis of biomedical image sequences (4D-FAMIS).
      HeLa and SiHa cells containing, respectively 20-50 and 1-2 copies per cell of
      human papillomavirus (HPV) DNA type 18 and 16 integrated in cellular DNA were
      used as models. HPV-DNA was identified using DNA probes containing the whole
      genome of HPV-DNA type 18 or 16, and DNA-DNA hybrids were revealed by alkaline
      phosphatase and Fast Red. Cell nuclei were counterstained with thiazole orange
      (TO) or TOTO-iodide. 4D image sequences were obtained using successive dynamic or
      spectral sequences of images on different optical sections from CLSM. The
      location of fluorescent signals within the preparations was determined by FAMIS.
      This original method summarizes image sequences into a reduced number of images
      called factor images, and curves called factors. Factors estimate different
      individual physical behaviours in the sequence such as extinction velocity,
      spectral patterns and depth emission profiles. Factor images correspond to
      spatial distributions of the different factors. We distinguished between Fast Red
      and nucleus stainings in HPV-DNA hybridization signals by taking into account
      differences in their extinction velocities (fluorescence decay rate) or spectral
      patterns, and in their focus (depth emission profiles). In HeLa cells, factor
      images showed that Fast-Red-stained targets could be distinguished from nucleus
      stainings, and were located on different focal planes of the nuclei. In SiHa
      cells, 4D-FAMIS determined as few as 1-2 copies per cell of HPV-DNA type 16
      located in continuous focal planes. Therefore, 4D-FAMIS, together with CLSM, made
      the detection and characterization of low copy numbers of genes in whole cells
      possible.

PMID- 10199003
TI  - Ultrastructural characterization of isolated rat Kupffer cells by transmission X
      ray microscopy.
AB  - The ultrastructure of primary cultured rat Kupffer cells was studied using
      transmission X-ray microscopy as well as transmission electron microscopy. X-ray
      microscopical images of intact, hydrated Kupffer cells demonstrated structures
      such as cell nucleus separated by a nuclear membrane and filaments concentrated
      in the perinuclear area. Within the cytoplasm, a number of vacuoles were visible;
      some of these were crescent-shaped vacuoles that were half X-ray lucent, half X
      ray dense; others were uniformly dense. The number of crescent-shaped vacuoles
      was predominant. After phagocytosis of haematite particles, enlarged vacuoles
      containing the ingested material were visible within the cytoplasm of Kupffer
      cells while crescent-shaped vacuoles were no longer detectable. Densitometric
      analysis of the two types of vacuole revealed that the X-ray absorption of the
      uniform vacuole was approximately half that of the dense part of the crescent
      shaped vacuoles. This observation led to speculation on the existence of only one
      type of vacuole in the cytoplasm of Kupffer cells. The different morphological
      aspects--crescent-shaped versus uniform vacuoles--might be due to different three
      dimensional orientation with respect to the image plane. Using transmission
      electron microscopy, the morphology of vacuoles differed more widely in diameter,
      density and shape. Two main types of vacuole were identified: electron-lucent and
      electron-dense. Based on the observation of only one type of vacuole by
      transmission X-ray microscopy, the different morphological aspects of vacuoles
      obtained by transmission electron microscopy could be explained by imaging
      several different sections of a crescent-shaped vacuole. From the present data it
      can be concluded that transmission X-ray microscopy is a versatile technique that
      reveals the ultrastructure of intact, unsectioned biological specimens in their
      aqueous environment, thereby allowing a more comprehensive interpretation of data
      obtained by transmission electron microscopy.

PMID- 10199004
TI  - Retaining ionic concentrations during in vitro storage of tissue for
      microanalytical studies.
AB  - When human or animal tissue is to be investigated by X-ray microanalysis, it is
      sometimes necessary to store the tissue between removal from the organism and
      freezing. However, when excised tissue is stored in buffer, the elemental
      concentrations in the cell may change. In the present study, it was attempted to
      develop a storage buffer that would retain the cellular elemental concentrations
      close to their in situ values. To start, the NaCl component in Krebs-Ringer
      buffer was exchanged for K-gluconate and KCl for NaCl. This buffer was called a
      '100% high K+ solution'. Starting from this solution, part of the K-gluconate was
      replaced by an equivalent amount of NaCl. Incubation of excised rat liver (4
      degrees C, 4 h) in 85% high K+ solution resulted in retention of cellular Na, K,
      Ca, S and Mg concentration most closely to the in situ state, whereas cellular Cl
      was retained best when the tissue was incubated in 75% high K+ solution. For rat
      submandibular gland, incubation in 80% high K+ solution resulted in optimal
      retention of cellular Na, K, Ca, P, S and Mg, while Cl was retained best in a 70%
      high K+ solution. Based on these results, an optimally modified Krebs-Ringer
      solution for the liver would consist of 119 mM K+, 26 mM Na+ and 45 mM Cl-. An
      optimally modified Krebs-Ringer bicarbonate solution for the submandibular gland
      would be composed of 96 mM K+, 53 mM Na+ and 46 mM Cl-. After incubation in the
      modified solutions (at 4 degrees C), cellular Na, Mg, S, Cl, K and Ca in both
      tissues were maintained close to the in situ state throughout a 6-h incubation.
      The cellular P concentration was reduced after incubation for 1 h; thereafter, in
      the liver cells it remained at this lower level for the rest of the incubation,
      whereas in the submandibular gland tissue it increased again after 4 h. The
      increase in cell volume (oedema) was less in tissue stored in the modified
      solutions, than in the 100% high K+ solutions. Incubation in high Na+ buffers (4
      degrees C, 6 h) resulted in a progressive increase in the percentage of cells
      showing trypan blue uptake. A similar increase in trypan blue uptake was seen in
      the modified solution, but this increase levelled off after 4 h. After
      cholinergic stimulation in high Na+ solution (25 degrees C, 1 min), the expected
      decrease in cellular Cl concentration was seen in submandibular gland cells that
      had previously been preserved (4 degrees C, 4 h) in the modified solution, but
      not in those that had been preserved in the 100% high K+ solution.

PMID- 10199005
TI  - Population structure of North American beluga whales (Delphinapterus leucas)
      based on nuclear DNA microsatellite variation and contrasted with the population
      structure revealed by mitochondrial DNA variation
AB  - Beluga whales (Delphinapterus leucas) in North American waters migrate seasonally
      between wintering areas in broken pack ice and summering locations in estuaries
      and other open water areas in the Arctic and sub-Arctic. Results from our
      previous investigation of beluga whale mitochondrial DNA (mtDNA) revealed genetic
      heterogeneity among beluga from different summering locations that was
      interpreted as representing a high degree of summering site philopatry. However,
      mtDNA is maternally inherited and does not reflect mating that may occur among
      beluga from different summering locations in wintering areas or during annual
      migrations. To test the possibility that breeding occurs among beluga from
      different summering locations, genetic variability at five nuclear DNA (nDNA)
      microsatellite loci was examined in the same animals tested in the mtDNA study.
      Beluga samples (n = 640) were collected between 1984 and 1994 from 24 sites
      across North America, mostly during the summer. Whales from the various sites
      were categorized into eight summering locations as identified by mtDNA analysis,
      as well as four hypothesized wintering areas: Bering Sea, Hudson Strait (Hudson
      Strait, Labrador Sea, southwest Davis Strait), Baffin Bay (North Water, east
      Davis Strait), and St Lawrence River. Microsatellite allele frequencies indicated
      genetic homogeneity among animals from summering sites believed to winter
      together but differentiation among whales from some of the wintering areas. In
      particular, beluga from western North America (Bering Sea) were clearly
      distinguished from beluga from eastern North America (Hudson Strait, Baffin Bay,
      and St Lawrence River). Based upon the combined data set, the population of North
      American beluga whales was divided into two evolutionarily significant units.
      However, the population may be further subdivided into management units to
      reflect distinct groups of beluga at summering locations.

PMID- 10199006
TI  - The population genetic structure of a large temperate pollinator species, Bombus
      pascuorum (Scopoli) (Hymenoptera: Apidae)
AB  - The genetic population structure of the bumble bee Bombus pascuorum was studied
      using six microsatellite loci and a partial sequence of the mitochondrial gene
      cytochrome b. Eighteen populations from central and northern Europe were included
      in the analysis. Observed levels of genetic variability and heterozygosity were
      high. Estimates of population differentiation based on F- and phi-statistics
      revealed significant genetic differentiation among B. pascuorum populations and
      suggest that two partially isolated gene pools, separated by the Alps, do exist.
      The distribution of mtDNA haplo-types supports this view and presents direct
      evidence for gene flow across the Alps. Estimates of the number of migrants
      exchanged among populations north of the Alps suggest that historical events may
      have left a strong imprint on population structure.

PMID- 10199007
TI  - Genetic differentiation within and between isolated Algerian subpopulations of
      Barbary macaques (Macaca sylvanus): evidence from microsatellites
AB  - This study of wild-living Algerian Barbary macaques (Macaca sylvanus) was
      designed to examine genetic variability in subpopulations isolated in residual
      forest patches, in an attempt to obtain data on the effects of habitat
      fragmentation. The wild population of this species (estimated at a maximum of
      15,000) is vulnerable and this study therefore has direct relevance for
      conservation measures. Data from five microsatellite loci were analysed for 159
      individuals from nine different groups living in four isolates in Algeria.
      Genetic polymorphism was found to be relatively high (4-12 alleles per locus)
      compared with other genetic markers used in previous studies of this species;
      mean expected heterozygosity was 65%. The four isolates are all genetically
      distinct (FST = 0; P < 0.001). Indeed, the results suggest that dispersal is
      limited even between some social groups within a single isolate. Genetic
      distances based on models not assuming stepwise mutation (FST and chord distance)
      gave very similar results and are highly correlated with geographical distances
      within one isolate but not between isolates. This may indicate that isolation by
      distance exerts a significant influence within an isolate but that genetic drift
      prevails between the four isolates. After allowing for variation in sample size,
      we found no evidence of reduced allelic diversity within small isolates that may
      have been separated for 250 years or more. The surviving population of Algerian
      Barbary macaques taken as a whole still shows marked variability in
      microsatellite alleles, but maintenance of genetic variability over the long term
      will surely require effective protection of all isolates.

PMID- 10199008
TI  - Amplified fragment length polymorphism (AFLP) analysis of genetic variation in
      Moringa oleifera Lam
AB  - Moringa oleifera is an important multipurpose tree introduced to Africa from
      India at the turn of this century. Despite limited knowledge of the levels of
      genetic diversity and relatedness of introduced populations, their utilization as
      a source of seed for planting is widespread. In order to facilitate reasoned
      scientific decisions on its management and conservation and prepare for a
      selective breeding programme, genetic analysis of seven populations was performed
      using amplified fragment length polymorphism (AFLP) markers. The four pairs of
      AFLP primers (PstI/MseI) generated a total of 236 amplification products of which
      157 (66.5%) were polymorphic between or within populations. Analysis of molecular
      variance (AMOVA) revealed significant differences between regions and
      populations, even though outcrossing perennial plants are expected to maintain
      most variation within populations. A phenetic tree illustrating relationships
      between populations suggested at least two sources of germplasm introductions of
      Kenya. The high levels of population differentiation detected suggest that
      provenance source is an important factor in the conservation and exploitation of
      M. oleifera genetic resources.

PMID- 10199009
TI  - Identification of roots of woody species using polymerase chain reaction (PCR)
      and restriction fragment length polymorphism (RFLP) analysis
AB  - Within the last two decades, substantial progress has been made in understanding
      seed-bank dynamics and the contribution of the soil seed bank to a
      postdisturbance plant community. There has been relatively little progress,
      however, in understanding perennial bud-bank dynamics and the contribution of the
      soil bud bank to secondary succession. This lack of information is due primarily
      to the inability to reliably identify roots, rhizomes and lignotubers that lie
      dormant beneath the soil surface. This investigation addressed the issue of
      identification of below-ground woody structures. The first objective was to
      develop a method that used molecular tools to identify woody plant species from
      subsoil tissue samples. The second objective was to develop a key in which
      molecular markers served as criteria for the identification and differentiation
      of selected tree and shrub species common to the mountains of northeast Oregon
      and southeast Washington. Application of restriction fragment length polymorphism
      (RFLP) analysis of polymerase chain reaction (PCR)-amplified rbcL appears to be a
      reliable method to identify and differentiate 15 plants to the genus level. Two
      restriction enzymes, DpnII and HhaI, provided restriction site polymorphisms in
      the PCR product. The fragment number and length were used to develop an
      identification key. However, plants not analysed in this 'exploratory key' might
      share the same banding patterns, resulting in a false identification of unknowns.

PMID- 10199010
TI  - Features of DNA fragments obtained by random amplified polymorphic DNA (RAPD)
      assays
AB  - Random amplified polymorphic DNA (RAPD) fragments were prepared from samples of
      Calonectris diomedea (Cory's shearwater, Aves) and Haemonchus contortus
      (Nematoda) DNA by polymerase chain reaction (PCR) using decamers containing two
      restriction enzyme sites as primers. Six of 19 studied RAPD fragments probably
      originated from traces of commensal microorganisms. Many rearranged fragments,
      absent in the original genomic DNA, were synthesized and amplified during the
      processing of all the DNA samples, indicating that interactions occur within and
      between strands during the annealing step of PCR. The model of interactions
      between molecular species during DNA amplification with a single arbitrary
      oligonucleotide primer was modified to include nested primer annealing and
      interactions within and between strands. The presence of these artefacts in the
      final RAPD have a major effect on the interpretation of polymorphism studies.

PMID- 10199011
TI  - Polymorphic chloroplast simple sequence repeat primers for systematic and
      population studies in the genus Hordeum
AB  - In this study we report the development of primers to amplify polymorphic
      chloroplast simple sequence repeats in the genus Hordeum, which includes
      cultivated barley (H. vulgare ssp. vulgare) and its wild progenitor H. vulgare
      ssp. spontaneum. Polymorphic products were amplified in a wide range of Hordeum
      spp. and intraspecific variation was detected in both cultivated and wild barley.
      A decrease in cytoplasmic diversity was observed between sspp. spontaneum and
      vulgare as well as between ssp. vulgare landraces and cultivars, which is
      characteristic of domestication processes in many corp species. We also observed
      possible evidence for reticulate evolution of H. brachyantherum polyploids, with
      apparent multiple cytoplasmic introgressions during successive polyploidization
      events.

PMID- 10199012
TI  - Isolation of microsatellite loci for paternity testing in the rufous vanga
      Schetba rufa

PMID- 10199013
TI  - Microsatellite markers in Stylosanthes guianensis

PMID- 10199014
TI  - Isolation and characterization of microsatellite loci in Didelphis marsupialis
      (Marsupialia: Didelphidae)

PMID- 10199015
TI  - Development and cross-species comparison of microsatellite markers in two lizard
      species, Lacerta vivipara and Podarcis muralis

PMID- 10199016
TI  - Four primer pairs for the amplification of chloroplast intergenic regions with
      intraspecific variation

PMID- 10199017
TI  - Polymorphic microsatellite markers for the banana pathogen Mycosphaerella
      fijiensis

PMID- 10199018
TI  - [Recommendations for the use of the varicella vaccine in immunosuppressed
      patients].

PMID- 10199019
TI  - [Transplant of hematopoietic stem cells from cord blood].

PMID- 10199020
TI  - [Febrile seizures: is EEG useful?].
AB  - OBJECTIVE: The purpose of this study was to determine the clinical relevance of
      electroencephalograms (EEG) with generalized spike-wave (S-W) in pediatric
      patients, especially in children with febrile seizures. PATIENTS AND METHODS: One
      hundred and seventy pediatric patients with S-W were found from a register of
      39,322 consecutive EEGs performed in an EEG laboratory dedicated to general
      clinical practice. Patients that only suffered febrile seizures were not
      considered epileptic. RESULTS: Of the 170 patients, 154 (90.6%) were epileptic
      and 16 (9.4%) were not. Mean follow-up was 4.5 years. Twelve of the 16 non
      epileptic children with S-W suffered febrile seizures. CONCLUSIONS: The presence
      of S-W in EEGs is uncommon. Almost 10% of the children with S-W were not
      epileptic patients and none of them suffered from epilepsy during the follow-up
      period. Performance of an EEG on a child without epilepsy, especially those with
      febrile seizures, can be a factor of confusion.

PMID- 10199021
TI  - [Screening for adolescent idiopathic scoliosis: is current knowledge sufficient
      to support its use?].
AB  - OBJECTIVE: The aim of this study was to re-examine the basis of screening for
      adolescent idiopathic scoliosis. PATIENTS AND METHODS: Retrospective analysis of
      scoliosis screening of patients with a positive test was performed. The screening
      was performed in children between 10 and 15 years by visual inspection of the
      back and the Adams forward-bending test. RESULTS: In 31.6% of the children, the
      screening test detected the presence of abnormal findings on initial physical
      examination. 19% of the total population was sent to a traumatology service. In
      11% the diagnosis was confirmed (16 scoliosis, 12 of them idiopathic and 4 due to
      other conditions), PPV: 58%. In 8% of the adolescents exercise was recommended.
      In 1.2% braces were recommended. There were no differences in prevalence between
      sex, but the height of the children with scoliosis was greater (p < 0.001).
      CONCLUSIONS: Because of the potential severe adverse effects and because the
      studies of the efficacy of the screening are not reliable, the U.S. Preventive
      Services Task Force, Canadian Task Force and the Program de Actividades
      Preventivas y Promocion de la Salud have excluded the routine screening of the
      asymptomatic adolescent for idiopathic scoliosis.

PMID- 10199022
TI  - [Automated system of bone maturity evaluation applied to the Tanner-Whitehouse 2
      method].
AB  - OBJECTIVE: Employing automated methods of image analysis to determine bone
      maturity helps to avoid subjectivity, reduce the execution time and to increase
      continuity in maturity scales. We have studied bone maturity by the Tanner
      Whitehouse method (TW2) and by image analysis based on Fourier transformation.
      PATIENTS AND METHODS: Bone maturity (BM) was evaluated in 200 X-rays of the left
      hand and wrist from 45 children between 2 and 18 years of age employing the TW2
      method, manual or traditional, to determine the state of maturity of each bone.
      At the same time, BM was evaluated by using an automated form of a recognizance
      program (IMAGO 2). As a standard we used the schemes of the phases described in
      the TW2 method. The image of the bone in question captured by a video camera
      after digitalization was classified by statistical comparison of its Fourier
      coefficient matrix with that previously determined by each of the standard
      schemes. Manual and computerized bone age concordance was also studied. RESULTS:
      The computerized procedure showed a tendency to give lower values than the manual
      procedure. There were no significant differences between mean phases when
      calculated by both methods (manual and computerized) for the radius and the fifth
      metacarpal. The least degree of concordance was observed in the third metacarpal
      and phalanges. We found better concordance in the carpal bones than in the
      phalanges. This concordance was lower than that found in the radius and fifth
      metacarpal. The worst results were observed in the carpus and large bones and the
      best results were observed in the semilunar and scaphoid bones. CONCLUSIONS:
      Divergence in the reproducibility between this computerized system and others
      (CASES method) are probably related to the differences between the digitalization
      process and the standard images used.

PMID- 10199023
TI  - [Accidental punctures: ten years of experience with our protocol].
AB  - OBJECTIVE: We report our experience during the past 10 years in the management of
      accidental punctures. PATIENTS AND METHODS: A study was made of all hypodermic
      needle punctures recorded in children aged 0-14 years in our center since 1987. A
      clinical protocol consisting of 5 visits and duration of 6-7 months was used in
      all cases. RESULTS: A total of 150 punctures were recorded during the study
      period with a decrease in prevalence over time. All cases the clinical protocol
      was accepted and correct follow-up procedures were performed. In no case was post
      puncture sero-conversion detected for HCV, HBV, or HIV among correctly immunized
      children. CONCLUSIONS: The protocol employed is useful and well accepted with the
      risk of infection caused by accidental puncture being remote provided initial
      patient care was adequate.

PMID- 10199024
TI  - [Attention deficit hyperactivity disorder. A survey to evaluate risk factors,
      associated factors and parental child rearing behavior].
AB  - OBJECTIVE: The aim of this study was to determine the relationship between
      several adversity factors and Attention Deficit Hyperactivity Disorder (ADHD), to
      evaluate the existence of associated factors and to investigate parental rearing
      behaviors. PATIENTS AND METHODS: Eighty subjects between 7 and 8 years of age
      were studied. These patients belonged to a transversal study of 263 subjects that
      had completed the Revised Conners' Parent and Teacher Rating Scales. The authors
      evaluated the presence of seven probable adversity factors including: low socio
      economic status, large family size, history of psychiatric disorders in first
      grade family members, drug abuse in parents, presence of psychological problems
      in the mother, perinatal pathology in the child and "difficult" temperament
      during early childhood. The associated factors studied were accident proneness,
      left motor preference, soft neurological signs, low vocabulary coefficient, poor
      academic achievement, low self-esteem, symptoms of anxiety and depression. EMBU-P
      questionnaires were used to assess parental rearing behavior. RESULTS: Two
      adversity factors were present in a statistically significant proportion, large
      family size and "difficult" temperament in early childhood, as well as two
      associated factors, left-handedness and low self-esteem. No statistically
      significant association between parental rearing behavior and ADHD was observed.
      CONCLUSIONS: It is necessary to keep in mind the different risk factors and
      associated factors of ADHD which could help to make an early diagnosis of the
      disorder which is very important because of its high prevalence and co-morbility.

PMID- 10199025
TI  - [Social characteristics and health status of children entering foster care
      centers].
AB  - OBJECTIVE: The purpose of this study was to assess the social characteristics and
      health status of children entering foster care. PATIENTS AND METHODS: A cross
      sectional study was performed over a 6-year period. Data was collected using a
      standardized entrance form. Using the child's medical history and a physical
      examination according to standardized protocols their health status was assessed.
      RESULTS: The following results were obtained on 776 children. Demography: 53.6%
      males and 46.4% females; mean age 7.3 +/- 5.7 years and predominance of
      infants/preschoolers (46.1%) and adolescents (32.9%). Family characteristics:
      living in a single parent family (33.2%) or no parent family (18.4%) before
      placement; coming from a high-risk family (53.7%) and/or a family with multiple
      problems (33.9%). Reason for placement: neglect (50.2%), parental incapacity
      (24.2%), abandonment (22%), physical abuse (20.1%), child disruptive behavior
      (17%), emotional abuse (11%), sexual abuse (3.2%) and more than one reason
      (33.1%). Personal history: chronic illness (4.4%), incomplete immunization
      (20.1%), psychomotor delay (4.2%), special education (3.3%), and delay/precocious
      school abandonment (34.6%). Health status: abnormality in at least one body
      system (66.1%) and more than one (42%), the most frequent health problems
      included problems in odontology (38.1%), dermatology (29.9%), vision (18.4%),
      respiration (11.6%), orthopedics (10.5%), psychomotor delay (10.3%), otology
      (8.1%) and ocular (6%). Actions taken included: therapeutic prescription for
      acute illness (43.7%) and referral to other sanitary services (46.9%).
      CONCLUSIONS: A high rate of children entering foster care present physical and
      mental health problems. These problems can be identified at the time of entrance
      into foster care; therefore, early intervention in the treatment and referral of
      this high-risk population must be undertaken as a great opportunity to solve
      them.

PMID- 10199026
TI  - [Screening for retinopathy of prematurity: reliability].

PMID- 10199027
TI  - [Wiedemann-Beckwith syndrome: clinical and epidemiological analysis of a
      consecutive series of cases in Spain].
AB  - OBJECTIVE: Wiedemann-Beckwith syndrome is a multisystemic pattern of congenital
      anomalies with overgrowth. The most characteristic clinical features are
      macroglossia, high birth weight, omphalocele, visceromegaly and hypoglycemia.
      PATIENTS AND METHODS: We show the clinical and epidemiological characteristics of
      the 18 cases with Wiedemann-Beckwith syndrome identified in the consecutive
      series of 25,967 malformed liveborn infants detected among 1,431,368 livebirths
      surveyed by the Spanish Collaborative Study of Congenital Malformations (ECEMC)
      between April 1976 and June 1997. RESULTS AND CONCLUSIONS: The minimal estimated
      frequency of Wiedemann-Beckwith syndrome in Spain is 0.13 per 10,000 liveborn
      infants. These infants have a high birth weight for their gestational age and are
      born of shorter pregnancies (prematurity 33.3%). The clinical manifestations of
      our cases are concordant with the variable expression of the syndrome; the most
      frequent features were macroglossia (100%), omphalocele or umbilical hernia
      (77.8%) and high birth weight (64.7%). Other findings were polyhydramnios and
      placentomegaly. All of the cases were sporadic.

PMID- 10199028
TI  - [Early detection of hearing loss in neonates by using transient evoked
      otoacoustic emissions].
AB  - OBJECTIVE: A precocious diagnosis of infantile deafness is essential to avoid its
      implications in the family and the social and employment future of those that
      suffer from them. The discovery of new tests that can be used for auditory
      screening, such as otoacoustic emission, has opened new perspectives in this
      field. PATIENTS AND METHODS: Universal screening was performed including neonates
      born in our area. We studied 7,153 children (296 with indicators of risk) born
      between 1995 and 1997. Our protocol was based on transient evoked otoacoustic
      emissions as the screening method and brainstem auditory evoked potentials as the
      diagnostic procedure. RESULTS: Two out of 1000 ears studied presented
      serious/deep deafness and 1.39 per 100 had some type of hearing loss. The
      incidence of pathology was higher among ears of children with risk factors: 1.8
      per 100 had serious/deep deafness and 7.59 per 100 some type of hearing loss.
      CONCLUSIONS: Transient evoked otoacoustic emission is an effective method when
      used in infantile auditory screening, since it is objective, bloodless and quick.
      Its correlation with auditory evoked potentials is very high, which proves their
      reliability. The best moment to perform this test (OAE) is when the discharge
      from the hospital is certified. We believe that universal screening is necessary,
      although a much higher incidence of deafness is encountered among children with
      risk factors. The establishment of programs for the precocious detection of
      infantile deafness should not be delayed.

PMID- 10199029
TI  - [Pediatric psoas abscess. Our experience with two cases].

PMID- 10199030
TI  - [Primary mesenteric solid tumors in childhood: a case of mesenteric lipoma
      approached by laparoscopy].

PMID- 10199031
TI  - [Cardiac fibroma: diagnosis and surgical treatment].

PMID- 10199032
TI  - [A case of inverted tandem partial duplication of 12p].

PMID- 10199033
TI  - [Cystic adenomatoid malformation of the lung with systemic arterial blood
      supply].

PMID- 10199034
TI  - [Bilateral maxillary tumefaction].

PMID- 10199035
TI  - [Treatment protocol for pneumonia in childhood. Work group "Pneumonias"].

PMID- 10199036
TI  - [Current issues of resuscitation].
AB  - Reanimatology is a science dealing with prevention and correction of severe
      homeostasis disorders, nonspecific reactions of the organism to disease, injury,
      wounding, with general regularities of vital functions fading in the course of
      dying and their recovery after resuscitation. Five main sections of reanimatology
      are formulated: resuscitation, intensive care, anesthesiology, urgent medicine,
      and medicine of disasters. Specialization in reanimatology is determined by
      methods of treatment. Four trends are distinguished among the pressing problems
      of reanimatology: fundamental studies, development of methods for prevention and
      treatment of critical, terminal, and post-reanimation states, ethical and legal
      problems, and management. Results of recent studies are presented and prospects
      for the future are discussed.

PMID- 10199037
TI  - [Logic of the development of intensive care in critical states].

PMID- 10199038
TI  - [Stages of disseminated intravascular coagulation after resuscitation in patients
      with massive hemorrhage and severe multiple trauma].
AB  - Changes in blood coagulation and fibrinolysis were followed up in 255 patients of
      intensive care wards during 5 days after effective treatment of grave and
      terminal stages of traumatic hemorrhagic shock. Four stages in the development of
      disseminated intravascular coagulation (DIC) were distinguished. Special
      attention is paid to the time course of the third stage with repeated
      hypercoagulation, suppressed fibrinolysis, and microthrombolysis in organs and
      tissues leading to multiple organ failure. The fourth stage of DIC is described,
      when involvement of the organs and generalized inflammation or sepsis is
      associated with remote (on days 3-5 and later) hemorrhages. These hemorrhages are
      apparently caused by disorders in fibrin production but not by acute fibrinolysis
      and consumption coagulopathy, as during the second stage of DIC.

PMID- 10199039
TI  - [Optimization of artificial respiration parameters in patients with acute
      pulmonary parenchymal damage syndrome].
AB  - The relationship between the mean pressure in the trachea, generated in
      mechanical ventilation of the lungs (Ptr.m), and normal arterial oxygenation is
      linear in ventilated patients with severe bilateral acute parenchymatous damage
      to the lungs. Under conditions of mechanical ventilation of the lungs (MVL) with
      regulated volume, constant end-expiratory pressure (PEEP) and inspiratory pause
      (eIP) are effective methods for regulating Ptr.m. However, the efficacy of
      regulating Ptr.m by PEEP and IF for each clinical case is different. The
      algorithm of using PEEP and IF for optimizing the respiratory pattern in this
      category of patients is not clear, too. The results indicate that optimization of
      MVL with controlled volume should be started with selecting the optimal level of
      PEEP for each patient. The level of Ptr.m should not be increased immediately at
      by of prolonging eIP, because the probability of compromising the hemodynamics is
      higher in such a case than the probability of improving blood oxygenation. Only
      after selecting the optimal PEEP is it permissible to try to improve arterial
      oxygenation by prolonging xx, because under such conditions the efficacy of
      prolonged inspiration is notably increased. Our data indicate that eIP no higher
      than 30% of the respiratory cycle (inspiration/expiration = 1.5/1) is the
      optimal. A further increase of eIP gives rise to a tendency towards decrease of
      arterial oxygenation and oxygen transport to tissues.

PMID- 10199041
TI  - [Clinical and prognostic significance of assessing early postresuscitation
      changes in parameters of blood lipid peroxidation].
AB  - Clinical and prognostic significance of early postresuscitation changes in static
      and dynamic parameters of blood plasma lipid peroxidation (LPO) is studied in
      cats subjected to 5-min clinical death from blood loss after preliminary 30-min
      hemorrhagic hypotension. Assessment of dynamic parameters of LPO in addition to
      the static ones notably improved the reliability of prediction of the course of
      postresuscitation disease.

PMID- 10199040
TI  - [Complement system during hemofiltration in patients with multiple organ
      failure].
AB  - Nine patients (8 men and 1 woman) were treated. Sepsis was diagnosed in 7 of
      them. All patients were subjected to forced ventilation of the lungs, 6 were in
      need of inotropic support. The severity of clinical status was 31 +/- 0.8
      according to APACHE II score. One patient survived. The main method of substitute
      renal therapy (SRT) was permanent hemofiltration with spontaneous arteriovenous
      perfusion. The results indicate manifest depletion of the complement system
      augmenting with the progress of multiple organ failure (MOF). Extracorporeal
      perfusion in SRT had no additional negative effects on the complement system
      damaged by disease. Nonselective penetration of individual complement fractions
      into the filtrate in the course of perfusion was noted. Therefore, the complement
      system is severely damaged in patients with MOF; it can modulate the SRT because
      of penetration of its individual fractions.

PMID- 10199042
TI  - [Correction of several parameters of homeostasis in patients with ischemic heart
      disease by different methods of extracorporeal treatment of blood].
AB  - Plasmapheresis, ultraviolet exposure of the blood, combination of these two
      methods, and plasmapheresis with removal of the upper layer of cells (partial
      cytapheresis) were added to routine treatment of 204 coronary patients. The above
      methods brought about good results, their efficacy being determined by the degree
      of myocardial involvement. A clear-cut effect of plasmapheresis on DIC, typical
      of such patients, is worthy of note.

PMID- 10199043
TI  - [Several aspects of the treatment of suppurative-septic complications with regard
      to the state of the immune system].
AB  - A total of 118 patients with grave combined injuries, massive blood loss, and
      peritonitis of different origin were examined and treated. Monitoring of clinical
      and immunological parameters showed their correlation with the severity of the
      clinical status. Assessment of the effects of antibiotics on the opsonophagocytic
      system of immunity helped select adequate antibacterial therapy and timely
      correct the treatment, thus notably improving the results.

PMID- 10199044
TI  - [Electrolyte disorders in the postresuscitation period after acute myocardial
      infarct].
AB  - Experiments on 25 dogs demonstrated that ion redistribution between the cellular
      and extracellular sectors develops during recovery after 5-min clinical death
      from acute coronary myocardial infarction. Early after resuscitation (5 min-9 h)
      sodium ion concentration in the cells increases, while that of potassium
      decreases. Later (9-24 h) part of potassium cations migrates from cells to cell
      to-cell space and both cellular and extracellular potassium fractions decrease.

PMID- 10199045
TI  - [Effects of active behavior in the postresuscitation period on the functional and
      morphological characteristics of the brain].
AB  - Efficacy of prolonged (days 10-60 after resuscitation) regular activation of
      behavior by labyrinth training of 4-staged food search conditioned reflex is
      studied in rats subjected to 15-min circulation arrest. This training affected
      the function of the central nervous system, which manifested by decreased anxiety
      and a higher activity in the open field test. This functional exercise prevented
      fall-out of neurons in the fifth layer of hemispheres, of cerebellar Purkinje's
      cells, and of pyramidal neurons in hippocampal sector CA1. These results support
      the hypothesis proposed by A. M. Gurvich on the possibility of regulating the
      postresuscitation recovery of the central nervous system by neurophysiological
      treatment of the brain.

PMID- 10199046
TI  - [Use of semax at a follow-up of patients with posthypoxic encephalopathy].
AB  - Effect of a neuropeptide semax is studied in 73 patients with various symptoms of
      posthypoxic encephalopathy in remote period. Fourteen of these patients developed
      a persistent vegetative state. The therapy was effective in patients with mnestic
      disorders; the drug effect was potentiated by an adaptogen oxiterm and by
      supraorbital electrophoresis. In some cases EEG showed episodes of paroxysmal
      activity after semax injection, and therefore, the first injection should be
      carried out with monitoring bioelectric activity of the brain.

PMID- 10199047
TI  - [Transthoracic ventricular defibrillation: effectiveness of bipolar sinusoidal
      impulse].
AB  - The efficacy of low-energy bipolar pulse is studied in 41 patients with sudden
      heart arrest caused by ventricular fibrillation (VF). Maximal energy of effective
      charges during defibrillation of patients with or without acute myocardial
      infarction and primary VF (30 episodes) was only 90 J x 1-2. For eliminating
      secondary VF (76 episodes), maximal energy of 165-195 J x 1-5 was needed in only
      25% patients. Total efficacy of charges of at least 115 J x 1-2 in patients with
      primary and secondary VF was 87%. The results indicate a high efficacy of low
      energy bipolar sinusoidal charges for elimination of VF in patients with acute
      myocardial infarction and other forms of coronary disease.

PMID- 10199048
TI  - [Low-energy laser irradiation of blood as a method of prevention of blood
      circulation decompensation in hemorrhagic shock].
AB  - Effect of low-intensity laser exposure of the blood on the central hemodynamics,
      oxygen transporting function of the blood, oxygen balance of the organism, and
      surface configuration of erythrocyte membranes was studied in dogs exposed to 2-h
      arterial hypotension (arterial pressure 40 mm Hg). Blood exposure was started
      from the tenth min of hypotension and went on for 45 min (group 2) or 120 min
      (group 3); group 1 was control. The best results were attained after 45-min laser
      exposure. A longer exposure creates prerequisites for complications, such as
      dysadaptation of the vascular tone and delayed decrease of hemoglobin
      concentration.

PMID- 10199049
TI  - [Individual resistance of the cardiovascular system to acute hemorrhage].
AB  - Monitoring by ultrasonic and laser Doppler flowmetry and biomicroscopy
      demonstrated that rats highly resistant to acute blood loss differ in principle
      from rats with low resistance by the life span, pattern of changes in arterial
      pressure, organ hemodynamics, and microcirculation. The pumping function of the
      heart is intact till the end of life in all highly resistant and in 65% poorly
      resistant rats. After arrest of massive hemorrhage, 35% poorly resistant animals
      develop low cardiac output syndrome. Poorly resistant rats with severe
      posthemorrhagic hypotension represent a risk group in need of special
      pathogenetic therapy.

PMID- 10199050
TI  - [Use of neoton and finoptin to correct metabolic disorders of the brain in
      craniocerebral injuries].
AB  - Experiments on 55 outbred adult white rats narcotized with calipsol (50 mg/kg
      intraperitoneally) showed that separate infusions of a synthetic creatine
      phosphate analog neoton (100 mg/kg) and calcium antagonist finoptin (0.1 mg/kg)
      into the carotid artery directly after infliction of dosed craniocerebral injury
      improve energy metabolism and limit the intensity of lipid peroxidation in the
      brain during the first hour of the posttraumatic period.

PMID- 10199051
TI  - [Role of hyperbaric oxygenation in mechanisms correcting the immunological
      reactivity in endotoxic shock and serum sickness].
AB  - The adaptation effect of hyperbaric oxygenation (3.0 Ata for 60 min) on white
      rats and mice with acute serum sickness is due to stimulation of non-pathogenic
      circulating immune complexes which do not fix the complement nor induce immune
      injuries to the kidneys. This promotes recovery of nephron ultrafiltration and
      decreases proteinuria. Hyperbaric oxygenation stimulates immunity in endotoxin
      shock by activating the humoral immunity and specific immune response.

PMID- 10199052
TI  - [Bio-impedancemetry in the assessment of aqueous sectors of the body].

PMID- 10199053
TI  - [Ways of correcting immunodeficiency at different stages of burns with the aim of
      prevention and treatment of sepsis].

PMID- 10199054
TI  - Angioedema: frightening and frustrating.
AB  - Angioedema can have a variety of causes, including drug reactions, food
      allergies, and C1 esterase inhibitor deficiency, but many cases are idiopathic.
      Swelling usually subsides in days if the offending agent can be removed. The
      throat is often involved, but few patients actually require intubation.

PMID- 10199055
TI  - Should methotrexate be a first-line treatment for rheumatoid arthritis?

PMID- 10199056
TI  - Should all diabetic patients take ACE inhibitors, even those without proteinuria?

PMID- 10199057
TI  - Management of perimenopause: focus on alternative therapies.
AB  - A variety of herbs and other "natural alternative medicines" are marketed
      directly to consumers and sold over-the-counter as treatments for perimenopausal
      symptoms. Far from being innocuous placebos, many of these substances have real
      physiologic effects, including potential adverse effects and drug interactions.
      Yet they are largely untested and, by law, totally unregulated. This article
      reviews a few of the untested substances your patients may be taking, along with
      established treatments.

PMID- 10199058
TI  - Diagnosis and treatment of glucocorticoid-induced osteoporosis.
AB  - Glucocorticoids are a mainstay in the treatment of many diseases, including
      pulmonary and rheumatologic disorders. Unfortunately, as many as 90% of long-term
      glucocorticoid recipients lose a significant amount of bone and incur an
      increased risk of fractures. This paper reviews the pathophysiology, diagnosis,
      and treatment of glucocorticoid-induced osteoporosis.

PMID- 10199059
TI  - Diagnosing and treating plantar fasciitis: a conservative approach to plantar
      heel pain.
AB  - Plantar fasciitis is the most common cause of pain at the weight-bearing surface
      of the heel, and may coexist with other sources of heel pain. This has led to a
      confusing array of treatment strategies, including surgery. We offer a simple,
      effective diagnostic and treatment algorithm that emphasizes nonsurgical
      treatment options for this often frustrating condition.

PMID- 10199060
TI  - Hypersensitivity syndrome to antiepileptic drugs: a review including new
      anticonvulsants.
AB  - Anticonvulsant hypersensitivity syndrome, a potentially fatal but rare reaction,
      manifests as rash, fever, tender lymphadenopathy, hepatitis, and eosinophilia. To
      manage hypersensitivity syndrome successfully, one must recognize the symptoms
      early, stop the offending drug immediately, and substitute a safe, alternative
      anticonvulsant medication. Hypersensitivity syndrome has not been described in
      patients taking benzodiazepines or the newer anticonvulsants gabapentin or
      topiramate, and these appear to be safe substitutes for drugs that cause the
      reaction.

PMID- 10199061
TI  - United Kingdom Prospective Diabetes Study (UKPDS). Effects of glucose and blood
      pressure control on complications of type 2 diabetes mellitus.
AB  - The United Kingdom Prospective Diabetes Study (UKPDS) showed that intensive
      treatment (i.e., glucose-lowering drugs, with a goal fasting blood glucose level
      of 108 mg/dL) decreases the microvascular complications of type 2 diabetes
      mellitus. We summarize the key study results and their implications for clinical
      management of type 2 diabetes mellitus.

PMID- 10199062
TI  - The clinical epidemiological investigation of diagnostic modalities in breast
      cancer detection--a comparison of ultrasonography and mammography.
AB  - We reviewed the medical records and images of 39 women with palpable breast
      masses, including 18 cases with breast cancer and 21 cases with benign breast
      mass, to compare diagnostic accuracy and clinical agreement between
      ultrasonography and mammography in breast cancer detection. We showed that the
      operating characteristics of ultrasonography, including sensitivity, specificity
      and positive likelihood ratio, were superior to that of mammography. We also
      confirmed that the established malignant criteria for malignancy, including
      lobulated shape, irregular contour and non-uniform internal echo in
      ultrasonography, and stellate mass in mammography, were statistically significant
      in distinguishing breast cancer from benign breast lesion. Moreover, the
      interobserver agreement kappa of ultrasonography and mammography were 0.64 and
      0.59, respectively. Ultrasonography was also superior to mammography in attaining
      clinical agreement between the different observers in breast cancer detection.

PMID- 10199063
TI  - [Serum protein fractions in patients with laryngeal cancer undergoing radiation
      therapy. Possibility as a prognostic factor].
AB  - The levels of 21 protein components of the sera of 45 patients with cancer of the
      larynx undergoing radiation therapy were determined by a single radial
      immunodiffusion method before and after radiation therapy. We examined the
      correlation between changes in serum protein fractions and the prognosis of the
      patients. The patients with cancer of the larynx were treated with external
      irradiation of 60Co gammer-rays. Total target doses were 60 Gy. The levels of the
      same protein components were also measured in 43 normal adult individuals as a
      control. All patients were observed for 5 years and 12 years following radiation
      therapy. In the pretreatment sera obtained from patients with cancer of the
      larynx, the concentrations of prealbumin (Prealb), antithrombin III (ATIII) and
      plasminogen (Pmg) were significantly lower than controls. However the
      concentrations of alpha 1-acid glycoprotein (alpha 1AG), alpha 1-antitrypsin
      (alpha 1AT), alpha 1-antichymotrypsin (alpha 1X), haptoglobin (Hp), fibrinogen
      (Fib) and hemopexin (Hx) were elevated. At the completion of radiation therapy,
      the alpha 1AG, alpha 1AT, alpha 1X, Hp, Fib and inter alpha trypsin inhibitor (I
      alpha I) were significantly elevated than those normal controls. In patients
      without recurrent cancer after radiation therapy, the alpha 1AT, ceruloplasmin
      (Cp), Fib, IgA and Hx levels measured before radiation therapy were significantly
      lower than those patients with recurrent cancer. In patients without recurrent
      cancer after radiation therapy, the alpha 1AT, Hp, Cp, IgG, and IgA levels
      measured after radiation therapy were reduced compared with those patients with
      recurrent cancer. In patients who had lived more than 5 years after radiation
      therapy, the alpha 1AT, Cp and Fib levels measured before radiation therapy
      reduced significantly compared with those who had died within 5 years. In those
      who had lived more than 5 years, the alpha 1AG, alpha 1AT, Hp, Fib, IgG, and IgA
      levels measured after radiation therapy were reduced significantly compared with
      those who died within 5 years. In cases of laryngeal cancer following a period of
      5 to 12 years after radiation therapy, multiple regression analysis was used to
      determine whether increased concentrations of serum protein fractions were
      associated with good prognosis for the original disease. AT III, Prealb, alpha
      1AG, albumin (Alb) and I alpha I before radiation therapy were positively
      correlated with survival, whereas Hx, Pmg, Cp, IgM, Cl inhibitor (ClInh), alpha
      1AT and Fib showed negative correlations. After radiation therapy, transferrin
      (Tf), Cp, Prealb, AT III and I alpha I were found to be positively associated
      with survival, whereas IgA, IgM, Pmg, alpha 1X and alpha 1AG were negative
      factors. From the elevation levels of acute phase proteins (alpha 1AT, Cp) and
      Fib and immunoglobulins (IgA, IgM) in the serum and lower levels of Prealb and AT
      III before and after radiation therapy, we may predict a relatively poor
      prognosis in these patients of laryngeal cancer.

PMID- 10199064
TI  - [Radiological study of destructive spondyloarthropathy in patients receiving a
      long-term of hemodialysis].
AB  - Patients receiving long-term hemodialysis were examined radiologically twice at 7
      years interval, in order to elucidate the natural history of destructive
      spondyloarthropathy (DSA). DSA is known as a serious spinal lesion characteristic
      to hemodialyzed patients. In this study, 239 patients receiving hemodialysis were
      subjected to the study. DSA was detected in 21 cases (8.8%), which was mainly
      localized in the middle or lower cervical spine. The incidence of DSA was
      increased in those receiving hemodialysis for more than 5 years. Fifty-four among
      them were re-examined 7 years after the initial examination, and DSA was found in
      20 cases (37%). Some of them complained of severe pain in the cervical or lumbar
      regions, and showed myelopathic signs. Seemingly, the destructive changes of DSA
      aggravates in proportion to the long duration of hemodialysis.

PMID- 10199065
TI  - [The hygienic tasks in support of the epidemiological-health wellbeing of the
      population at the current stage].

PMID- 10199066
TI  - [The estimation of the carcinogenic risk in relation to anthropogenic pollution
      of the atmosphere].
AB  - The paper assesses an additional risk of aerogenic exposure in the establishment
      of a poor epidemiological situation in the context of cancer morbidity, which
      accounts for 2 cases per 1000 individuals in the most polluted area. The analysis
      made it possible to reveal the areas showing an increased additional cancer risk
      by individual nosological entities and to determine the directions of hygienic
      and epidemiological studies.

PMID- 10199067
TI  - [An epidemiological study of cancer morbidity and mortality among the population
      living in areas close to thermal and atomic electric power stations].
AB  - Cancer mortality and morbidity rates were studied in the population residing in 2
      areas adjacent to thermoelectric stations and in 3 areas next to atomic power
      stations. They were shown to be higher in the population living in vicinity of
      the former than in the latter stations.

PMID- 10199068
TI  - [The health, hygienic and toxicological characteristics of the natural water from
      the upper Volga].
AB  - The paper provides sanitary and toxicological water characteristics in the city
      of Yaroslavl on the Volga River in 1993-1996. The water was shown to contain high
      levels of petroleum products, COD, and toxic substances. The water concentrations
      of phenol were no greater than the acceptable values. Those of metals,
      pesticides, and detergents did not exceed the sanitary standards.

PMID- 10199069
TI  - [The effect of the mineral composition of drinking water on the health of the
      population (a review)].

PMID- 10199070
TI  - [Industrial hygiene and the health status of workers on track power-driven
      equipment].
AB  - The study has revealed the leading poor occupational factors in workers of
      railroad power-driven stations, shows their nutritional status and pattern, and
      specific features of morbidity. It gives recommendations to optimize the
      alimentary status, to ensure the sanitary and epidemiological well-being and
      health of the workers.

PMID- 10199071
TI  - [Chronic fatigue in workers--an index for risk assessment].

PMID- 10199072
TI  - [Improvement in the hygiene training of workers in public eating establishments
      and the foodstuffs trade].
AB  - Experience gained in the hygienic training of those who are engaged at public
      catering enterprises and grocery stores in different regions of the Russian
      Federation is presented. Hygienic training courses have been set up in the State
      Sanitary and Epidemiological Surveillance centers. Programs for training workers
      at public catering enterprises and grocery stores have been approved by the board
      and the Russian Federation State Sanitary and Epidemiological Surveillance
      Committee and the Trade Committee of the Russian Federation.

PMID- 10199073
TI  - [The complex influence of school environmental factors on the health of
      children].
AB  - The combined influence of school environmental factors and a teaching process on
      children's health was studied in Orenburg. The study demonstrates there is a
      relationship between some physiological parameters in schoolchildren and the
      above factors and the level of educational burden. Measures to correct poor
      school factors are required.

PMID- 10199074
TI  - [The effect of the instructional profile in secondary schools on the body
      functional status of the pupils].
AB  - The main point of a lyceum is specialized education. The features of its
      educational process were studied by 6 profiles: medical, humanitarian,
      physicomathematical, chemobiological, technical, and commercial. The impact of
      either profile on the functional status of 2627 children was also examined. Study
      at the chemobiological, technical, and physicomathematical lyceums was shown to
      exert an unfavourable influence on the children's health.

PMID- 10199075
TI  - [The informational significance of metal bioaccumulation in the hair of preschool
      children].
AB  - Hair and urine metal accumulation was studied in healthy children living in
      different pollution areas. The levels of biogenic amines, the activity of the
      enzymes LDH, AP, and cholinesterase were also determined in the exhaled air
      condensate (EAC) and urine. High accumulation of metals, low EAC levels of
      biogenic amines, high activity of the urine enzymes were observed in the children
      residing in high polluted areas. At the same time these changes were less marked
      in the moderately polluted areas. The revealed changes allow one to select
      children at risk and to make health-promoting measures.

PMID- 10199076
TI  - [The subjective assessment by the population of the radiation risk].
AB  - The role of a subjective factor in the population's rating of various risk
      factors in radionuclide-polluted and radionuclide-free areas was studied. The
      residents from both areas consider to live in the radioactively polluted areas to
      be the first among risk factors. The coefficients of radiation risk rating by the
      population are 1.3-1.8.

PMID- 10199077
TI  - [The effect of certain factors on the radon concentration in the air of school
      premises].

PMID- 10199078
TI  - [The risk assessment of cancer morbidity in the joint action of carcinogens].

PMID- 10199079
TI  - [Volatile organic compounds in the air of the premises of residential and public
      buildings].

PMID- 10199080
TI  - [Toxicological hygiene studies of the alcohols produced by hydrolysis plants].

PMID- 10199081
TI  - [A new method for improving the visibility of the rolling stock in railroad
      transportation].

PMID- 10199083
TI  - [The organization of sanitary dosimetric control over the use of laser radiation
      in treatment and prevention institutions].

PMID- 10199082
TI  - [The microbial purification of sewage containing toxic substances].
AB  - The biotransformation of xenobiotics in the waste waters of gas-processing works
      was studied. Toxic pollutants were decontaminated by high-active aerobic and
      anaerobic microorganisms. The process for purifying industrial waste waters was
      effected at the Tengiz gas-processing works.

PMID- 10199084
TI  - [The prediction of the class of hazard of organic compounds by their structure].

PMID- 10199085
TI  - [An experimental study of the embryotoxic action of a complex of air pollutants
      in the Kryvyy Rih industrial region].

PMID- 10199086
TI  - [Toxicological studies as a stage in the hygienic expertise of polymeric
      materials for ship building].

PMID- 10199087
TI  - [The hygienic assessment of the working conditions for the workers of automatic
      telephone exchanges].

PMID- 10199088
TI  - [The hygiene education and training of the population: the problems and the means
      for implementation].

PMID- 10199089
TI  - [The validation of methodological measures for conducting social hygiene
      monitoring in Vologda Province].

PMID- 10199090
TI  - [The scientific and practical activities of the Center for State Epidemiological
      Health Surveillance in Shchelkovo District, Moscow Province].

PMID- 10199091
TI  - [The test exam as a stage in final state certification and the tasks in its
      improvement].

PMID- 10199092
TI  - [Measures to improve the medical care of adolescents].

PMID- 10199093
TI  - [The possibility of using risk assessments of the development of diagnostically
      different body states for setting hygienic standards].

PMID- 10199094
TI  - [The use of a rating system to control student knowledge in the teaching of
      hygiene].

PMID- 10199095
TI  - "Should medical journals try to influence political debates?".

PMID- 10199096
TI  - Family medicine in Hawaii.

PMID- 10199097
TI  - Patient privacy and confidentiality.

PMID- 10199098
TI  - Use of complementary and alternative medicine in Hawaii cancer patients.
AB  - This research investigated complementary and alternative medicine (CAM) use by
      Hawai'i cancer patients. Thirty-six percent of patients used CAM, most commonly
      religious/spiritual therapy and herbal treatments. CAM use was linked with
      younger age, female gender, Catholic religion, and more education. More research
      is needed to inform decision-making.

PMID- 10199099
TI  - Medical futility and the critically ill patient.
AB  - Today, the world of critical care medicine has given us the capabilities to
      accomplish things that were only dreamed of a few decades ago. When combined with
      the increasing importance of patient autonomy and economics in healthcare, these
      new capabilities have caused conflicts about what is too little, and what is too
      much. Medical futility becomes an issue whenever these conflicts arise.
      Understanding how to deal with issues surrounding futility begins with defining
      it. A firm definition is not possible or desirable, but revolves around the
      probability of being able to achieve a patient's goal with modern medicine.
      Establishing this understanding between the patient and their family (team), and
      the healthcare team, is dependent on trust between the two. It must be recognized
      that there are many reasons for families to not trust healthcare professionals
      and that these reasons need to be explored and dealt with. Sometimes conflicts
      regarding predictions and economics need to be addressed. Once trust is
      established a goal for a course of medical treatment should be discussed from the
      patient's perspective. This discussion should involve the physician's best
      judgement as to the chances of achieving this goal, and what type of discomfort
      or indignity, if any, the patient may experience. Only after these have been
      clearly discussed can decisions regarding medical futility be made. To date, the
      U. S. Courts have refused to grant physicians and hospitals the power to override
      the opinions of family members on matters of futility. However, with time, a
      consensus of public opinion should influence decisions regarding medical
      futility.

PMID- 10199100
TI  - Juvenile mania versus ADHD.

PMID- 10199101
TI  - More on valproate and polycystic ovaries.

PMID- 10199102
TI  - SSRIs and movement disorders.

PMID- 10199103
TI  - Methadone-induced hallucinations.

PMID- 10199104
TI  - Factitious hemoptysis.

PMID- 10199105
TI  - Pycnogenol for ADHD?

PMID- 10199106
TI  - No safe haven. II: The effects of violence exposure on urban youth.
AB  - OBJECTIVES: To examine the moderating effects of gender, grade level, and
      ethnicity on the associations between violence exposure and adolescents'
      internalizing symptoms and externalizing behavior and to explore whether such
      relationships persist over time. METHOD: A survey of adolescents' exposure to
      violence, internalizing symptoms, and externalizing behavior was administered to
      2 cross-sectional samples of 6th, 8th, and 10th graders (N = 2,748 in 1994 and
      2,600 in 1996) in an urban school system. Approximately 1,100 adolescents
      participated in both surveys and served as the longitudinal sample. RESULTS:
      Structural equation models indicated that violence exposure was closely
      associated with both externalizing behavior (r = 0.74-0.79) and internalizing
      symptoms (r = 0.36-0.38). The strength of association was similar across gender
      and ethnic groups. However, violence exposure was more closely related with
      internalizing symptoms for younger adolescents than their older counterparts. The
      longitudinal analysis suggested that exposure to violence reported at time 1 was
      related to adolescents' internalizing symptoms and externalizing behavior 2 years
      later. CONCLUSIONS: These results document high levels of violence exposure for
      urban youths and indicate links to a range of psychiatric symptoms and indicators
      of poor adjustment. Such findings carry implications for direct clinical work
      with young people, as well as for program development and public policy.

PMID- 10199107
TI  - Children's responses to a nuclear waste disaster: PTSD symptoms and outcome
      prediction.
AB  - OBJECTIVE: To examine the psychological impact of living near a nuclear waste
      disaster that involved ongoing threat of radioactive contamination. METHOD:
      Participants were an exposed sample (residence within a 5-mile radius of the
      nuclear plant) of 120 children (7-15 years old) and their parents and a
      nonexposed comparison sample of 60 children and their parents. Parent and self
      ratings of the children's psychological functioning and posttraumatic stress
      disorder (PTSD) symptoms were obtained, along with cognitive variables. RESULTS:
      Minimal differences between the 2 samples were found. In the exposed sample,
      stress responses for the child self-reports showed several age group by gender
      interactions. Girls' PTSD symptoms tended to increase with age while boys'
      symptoms decreased, with intrusion showing the strongest effects. While child and
      parent PTSD symptom ratings were correlated, children reported approximately
      twice as many symptoms. Cognitive understanding increased with age and was
      greater in boys. Exposure and parent functioning significantly predicted outcome.
      CONCLUSIONS: Age and gender effects after disaster might best be explored as an
      interaction. While disaster effects were mild, the psychological health of the
      parents may be an important determinant of psychological health in children in
      this type of disaster.

PMID- 10199108
TI  - Moral development and psychopathological interference in conscience functioning
      among adolescents after trauma.
AB  - OBJECTIVES: To compare moral development and psychopathological interference with
      conscience functioning (PI) among adolescents exposed to different degrees of
      earthquake-related trauma and to investigate the relationship of moral
      development and PI to exposure to trauma, severity of posttraumatic stress
      disorder (PTSD) symptoms, postearthquake adversities, and extent of loss of
      nuclear family members. METHOD: Adolescents (N = 193) from 2 cities at different
      distances from the epicenter were evaluated. The Stilwell Structured Conscience
      Interview was used to assess moral development and PI. Structured self-report
      instruments were used to obtain ratings of severity of earthquake-related trauma,
      posttraumatic stress symptoms, and postearthquake adversities. RESULTS:
      Adolescents in the city near the epicenter manifested advanced moral development
      as compared with their counterparts in the less affected city. Concomitantly,
      they endorsed responses indicating PI. Levels of PI were significantly correlated
      with severity of PTSD symptoms. CONCLUSION: In the aftermath of a catastrophic
      natural disaster, children assume greater responsibilities and confront a
      multitude of morally challenging interpersonal situations which may result in an
      advancement of their moral development. Yet, at the same time, PTSD symptoms and
      negative schematizations of self and others may give rise to disturbances in
      conscience functioning. The findings suggest that therapeutic consideration
      should be given to assisting children in integrating the horror of their
      traumatic experiences and the harshness of posttrauma adversities into an
      adaptive schema of good and evil in themselves and the world.

PMID- 10199109
TI  - Posttraumatic stress disorder in hospitalized adolescents: psychiatric
      comorbidity and clinical correlates.
AB  - OBJECTIVE: To describe the diagnostic comorbidity and clinical correlates of
      posttraumatic stress disorder (PTSD) in adolescent psychiatric inpatients.
      METHOD: Seventy-four adolescent inpatients were given a structured diagnostic
      interview, the revised version of the Diagnostic Interview for Children and
      Adolescents, and a battery of standard self-report measures to assess general
      trauma exposure, posttraumatic stress symptoms, suicidal behavior, dissociation,
      and depression. RESULTS: Ninety-three percent of subjects reported exposure to at
      least one traumatic event such as being a witness/victim of community violence,
      witnessing family violence, or being the victim of physical/sexual abuse. Thirty
      two percent of subjects met diagnostic criteria for current PTSD, with sexual
      abuse cited as the most common traumatic stressor in 69% of PTSD cases. Girls
      were significantly more likely to develop PTSD than boys, although the total
      number of types of trauma did not differ by gender. Compared with psychiatric
      controls, male youngsters with PTSD were significantly more likely to have
      comorbid diagnoses of eating disorders, other anxiety disorders, and somatization
      disorder. Furthermore, male and female youngsters with PTSD were significantly
      more likely to have attempted suicide and report greater depressive and
      dissociative symptoms. CONCLUSION: In clinical populations of hospitalized
      adolescents exposed to multiple forms of trauma, PTSD is a common, but highly
      comorbid disorder. Specific multimodal assessments and treatments targeted to
      both PTSD and its comorbidity profile are warranted.

PMID- 10199110
TI  - Predicting methylphenidate response in children with ADHD: theoretical,
      empirical, and conceptual models.
AB  - OBJECTIVE: To evaluate the theoretical merit and empirical validity of models
      designed to predict response to methylphenidate (MPH) among children with
      attention-deficit/hyperactivity disorder (ADHD). METHOD: Seventy-six children
      with ADHD received each of 4 counterbalanced doses of MPH (5, 10, 15, and 20 mg)
      in the context of a double-blind, placebo-controlled, within-subject (crossover)
      experimental design. Logical and conceptual foundations of 3 models of MPH
      response were subjected to critical scrutiny, and patterns of relationship
      anticipated on the basis of these models were subjected to empirical analysis.
      RESULTS: The conceptual foundations of all reviewed models were found to be
      substantially flawed, and none provided an adequate empirical basis for
      predicting response to MPH among children with ADHD. CONCLUSIONS: The observed
      pattern of relationships suggests that magnitudes of response to MPH in domains
      of classroom attention and behavioral disinhibition are correlated and
      differentially predictive of response on measures of academic performance and
      teacher-rated behavior.

PMID- 10199111
TI  - Response to methylphenidate in children with ADHD and comorbid anxiety.
AB  - OBJECTIVE: To determine whether comorbid anxiety alters response to
      methylphenidate (MPH) in children with attention-deficit hyperactivity disorder
      (ADHD). METHOD: Ninety-one children with ADHD were assessed for anxiety. Children
      were randomly assigned to receive MPH or placebo, titrated to a dose of 0.7
      mg/kg, while side effects were minimized. Measures of side effects and behavioral
      response were obtained from parents and teachers before treatment, after
      titration to optimal dose, and after 4 months of treatment. These measures, dose
      of drug, and rate of adherence to assigned medication assignment were compared
      for nonanxious (ADHD- ANX) and anxious ADHD children (ADHD+ ANX). RESULTS: Rates
      of adherence to original medication assignment did not differ between the groups.
      ADHD+ ANX on both MPH and placebo titrated to a lower dose at the end of
      titration, although the dose of drug did not differ among the groups after 4
      months of treatment. No differential response to MPH between ADHD+ ANX and ADHD-
      ANX was noted at end-titration or at 4 months on any side effect or behavioral
      measures. CONCLUSIONS: Comorbid anxiety does not appear to influence development
      of side effects or behavioral response to MPH when dose is titrated as in
      standard clinical practice.

PMID- 10199112
TI  - Behavioral inhibition in children from families at high risk for developing
      alcoholism.
AB  - OBJECTIVE: To determine whether children at risk for the development of adult
      alcohol dependence would show greater "behavioral inhibition" to the unfamiliar,
      an early childhood temperament characteristic. METHOD: One hundred peer play
      evaluations were conducted blindly with preschool children from families selected
      to be at high or low risk for developing alcohol dependence. Each child was
      paired with different children (same-sex pairs) in independent sessions to
      determine the stability of the behavioral response. RESULTS: High-risk children
      spent significantly more time staring at the other child during the peer play
      session while refraining from engaging in play, and significantly less time
      speaking to the other child. Significantly more time was spent proximal to the
      parent, but only on the first peer play session. These behaviors have been shown
      to be indicators of behavioral inhibition. CONCLUSIONS: These findings suggest
      that the presence of behavioral inhibition to the unfamiliar in childhood may be
      a risk factor for later development of alcohol dependence. While there is
      abundant evidence that childhood externalizing behaviors are risk factors for
      later development of substance dependence, the present results suggest that
      internalizing behaviors may be a pathway as well.

PMID- 10199113
TI  - Behavioral inhibition and developmental risk.

PMID- 10199114
TI  - Behavioral and emotional problems among children of cocaine- and opiate-dependent
      parents.
AB  - OBJECTIVE: To test associations between parental drug abuse and children's
      problems, children of cocaine- and opiate-dependent parents were compared with
      demographically matched referred and nonreferred children. METHOD: Cocaine- and
      opiate-dependent parents in treatment completed the Child Behavior Checklist for
      410 children (218 boys, 192 girls) from ages 2 through 18 years (mean = 7.9
      years). Children of drug abusers (CDAs) were demographically matched to referred
      (RCs) and nonreferred children (NRCs). RESULTS: RCs scored lower than CDAs and
      NRCs on most competence scales, and higher than CDAs and NRCs on all problem
      scales. CDAs scored lower than NRCs on most competence scales, and higher than
      NRCs on Withdrawn, Thought Problems, Delinquent Behavior, Aggressive Behavior,
      Internalizing, Externalizing, and Total Problems. Group status also predicted
      clinical range scores on most competence and all problem scales. CONCLUSIONS:
      CDAs showed more internalizing and externalizing psychopathology relative to
      matched NRCs, but they showed significantly less psychopathology than shown by
      matched RCs. CDAs are an important group to target for preventive interventions.

PMID- 10199115
TI  - Relationships between learning difficulties and psychological problems in
      preadolescent children from a longitudinal sample.
AB  - OBJECTIVES: To examine the relationships between learning difficulties and
      behavior problems in preadolescent children both concurrently and longitudinally,
      using data from the Australian Temperament Project, and to examine associations
      between DSM-diagnosed disorders and types of learning difficulties. METHOD:
      Clinical and comparison groups of 11- to 12-year-old children were assessed on
      behavioral and learning indices and completed a structured diagnostic interview.
      Longitudinal data were available from earlier surveys of the development of these
      children. RESULTS: Children in the clinical group were disadvantaged on all
      learning and behavioral indices, and their problems in many cases had been
      evident from 7 to 8 years of age. There were specific associations between types
      of learning difficulties and both internalizing and externalizing disorders.
      Numeracy difficulties were strongly associated with DSM diagnoses for both boys
      and girls, and externalizing problems tended to co-occur with a combination of
      learning problems. CONCLUSIONS: Behavioral maladjustment in many domains is
      strongly associated with learning difficulties even after intelligence and
      socioeconomic factors are controlled. The odds ratios for persistence of
      difficulties throughout elementary school are extremely high for children with
      clinical problems.

PMID- 10199116
TI  - Assessment of risk of eating disorders among adolescents in Appalachia.
AB  - OBJECTIVE: Students from 5 public schools in east Tennessee in grades 6 through
      10 were assessed for their risk of eating disorder. METHOD: The Eating Attitudes
      Test (EAT40), a self-administered questionnaire, was given anonymously to 1,302
      male and female adolescents. RESULTS: The results showed that 19.8% of females
      and 3.7% of males scored above 29, indicating high risk for development of an
      eating disorder. There was also a trend toward increased prevalence of risk in
      areas that are more rural. CONCLUSIONS: These findings suggest that the risk for
      eating disorders may be greater in rural areas than has previously been believed.
      This has implications for understanding the etiology of these diseases as well as
      demonstrating the need for more research in these often underserved areas.

PMID- 10199117
TI  - Psychiatric disorders among Japanese children.
AB  - OBJECTIVE: To generate current data on the prevalence of psychiatric disorders
      among Japanese children, using DSM-III-R criteria. METHOD: As part of an ongoing
      longitudinal study in a Japanese community sample, 114 mother-child dyads were
      interviewed when the children were approximately 8 years old. DSM-III-R disorders
      of the children were diagnosed through the administration of a structured
      diagnostic instrument, the parent and child versions of the Child Assessment
      Schedule, to both the children and their mothers. RESULTS: The prevalence rate
      for any diagnosis was 49.1%, which is similar to that of U.S. children and
      adolescents. CONCLUSION: The Child Assessment Schedule is an appropriate scale
      for assessing the psychopathology of Japanese children, which is as prevalent as
      in a U.S. sample.

PMID- 10199118
TI  - Thirty-three cases of body dysmorphic disorder in children and adolescents.
AB  - OBJECTIVE: Body dysmorphic disorder (BDD), a preoccupation with a nonexistent or
      slight defect in appearance, usually begins during adolescence. Because there
      have been no studies of the clinical features of BDD in children and adolescents,
      the authors assessed these features in the largest series to date. METHOD: Thirty
      three children and adolescents with DSM-IV BDD were assessed for demographic
      characteristics, phenomenology, associated psychopathology, and treatment history
      and response. RESULTS: Bodily preoccupations most often focused on the skin (61%)
      and hair (55%). All subjects had associated compulsive behaviors, most often
      camouflaging (e.g., with clothing) in 94%, comparing with others (87%), and
      mirror checking (85%). Ninety-four percent reported impairment in social
      functioning and 85% in academic or job functioning due to BDD. Thirty-nine
      percent had had psychiatric hospitalizations, and 21% had made a suicide attempt.
      Ten (53%) of 19 subjects treated with a serotonin reuptake inhibitor had much or
      very much improvement in BDD symptoms; in contrast, 0 of 8 trials with other
      psychotropic medications, 0 of 1 trial of cognitive-behavioral therapy, and 1 of
      20 psychotherapy trials resulted in improvement. Twelve (36%) subjects received
      surgical, dermatological, or dental treatment, with a poor outcome in all cases.
      CONCLUSIONS: BDD can cause significant morbidity in children and adolescents.
      These preliminary data suggest that serotonin reuptake inhibitors may be an
      effective treatment in this age group.

PMID- 10199119
TI  - Corticotropin-releasing hormone and cortisol: longitudinal associations with
      depression and antisocial behavior in pregnant adolescents.
AB  - OBJECTIVE: To examine the concurrent and longitudinal associations between
      corticotropin-releasing hormone (CRH) and cortisol concentrations and depression
      and antisocial behavior (conduct disorder symptoms) in pregnant adolescents.
      METHOD: Fifty-nine adolescents were evaluated in early pregnancy (9-21 weeks'
      gestation), late pregnancy (32-34 weeks' gestation), and the postpartum period (4
      5 weeks postpartum). Symptoms of depression and conduct disorder were obtained
      from the Diagnostic Interview Schedule for Children. RESULTS: Lower
      concentrations of CRH were related to a greater number of depression symptoms in
      early pregnancy (p < .05) and in late pregnancy (p < .05). Lower concentrations
      of CRH also were related to a greater number of conduct disorder symptoms in
      early pregnancy (p < .06) and in the postpartum period (p < .05). CONCLUSION: The
      findings support the long-standing hypothesis that stress-related products of the
      hypothalamic-pituitary-adrenal axis are associated with emotions and behavior
      during pregnancy.

PMID- 10199120
TI  - Further evidence of a bidirectional overlap between juvenile mania and conduct
      disorder in children.
AB  - OBJECTIVE: To investigate systematically the overlap between mania and conduct
      disorder (CD) in a sample of consecutively referred youths. It was hypothesized
      that neither CD nor manic symptoms were secondary to the other disorder and that
      children with the 2 disorders would have correlates of both. METHOD: Subjects
      were consecutively referred children and adolescents meeting DSM-III-R diagnostic
      criteria on structured diagnostic interview for CD (n = 116), mania (n = 110),
      and CD + mania (n = 76). RESULTS: Of 186 children and adolescents with mania and
      of 192 with CD, 76 satisfied criteria for both CD and mania, representing 40% of
      youths with CD and 41% of youths with mania, respectively. Examination of the
      clinical features, patterns of psychiatric comorbidity, and functioning in
      multiple domains showed that children with CD and mania had similar features of
      each disorder irrespective of the comorbidity with the other disorder.
      CONCLUSIONS: The data suggest that when mania and CD co-occur in children, both
      are correctly diagnosed. In these comorbid cases, CD symptoms should not be
      viewed as secondary to mania and manic symptoms should not be viewed as secondary
      to CD.

PMID- 10199121
TI  - Complex partial seizures in an adolescent psychiatric inpatient setting.

PMID- 10199122
TI  - Evaluating the validity of a research study.

PMID- 10199123
TI  - Genetics of childhood disorders: I. Genetics and intelligence.

PMID- 10199124
TI  - [Molecular biology and clinical diabetology].
AB  - Recent advancement of molecular biology highlighted three areas of basic research
      which may be important for clinical diabetology. One is the understanding of
      mechanisms of differentiation in pancreatic beta-cells and adipocytes. The second
      is the development of methods of tissue-specific knock-out mouse. This approach
      revealed that muscle may not be important for insulin-dependent glucose disposal
      in vivo. The third is the advancement of genetics which enabled to clone a major
      susceptibililly gene for type 2 diabetes mellitus (NIDDM1). These progress may
      bring new therapies for clinical diabetology.

PMID- 10199125
TI  - [Role of the NADH shuttle system in glucose-induced insulin secretion].
AB  - To determine the role of the NADH shuttle system composed of the glycerol
      phosphate shuttle and malate-aspartate shuttle in glucose-induced insulin
      secretion from pancreatic beta cells, we have generated mice which lack
      mitochondrial glycerol-3 phosphate dehydrogenase (mGPDH), a rate-limiting enzyme
      of the glycerol phosphate shuttle. When both shuttles were halted in mGPDH
      deficient islets treated with aminooxyacetate, an inhibitor of the malate
      aspartate shuttle, glucose-induced insulin secretion was almost completely
      abrogated. Under these conditions, although the flux of glycolysis and supply of
      glucose-derived pyruvate into mitochondria were unaffected, glucose-induced
      increases in NAD(P)H autofluorescence, mitochondrial membrane potential, Ca2+
      entry into mitochondria, and ATP content were severely attenuated. This study
      provides the first direct evidence that the NADH shuttle system is essential for
      coupling glycolysis with the activation of mitochondrial energy metabolism to
      trigger glucose-induced insulin secretion and thus revises the classical model
      for the metabolic signals of glucose-induced insulin secretion.

PMID- 10199126
TI  - [Clinical evaluation of insulin resistance].
AB  - Insulin resistance is a characteristic feature of NIDDM. Several methods to
      evaluate insulin resistance including euglycemic clamp study, Bergman's minimal
      model method, HOMA-R method and others. Some of these methods require long time
      which may be a disadvantage for the patients. More studies are necessary to prove
      that some of simple methods can be applied to all the patients with NIDDM.

PMID- 10199127
TI  - [Diabetes mellitus as a life-style related disease--importance of environmental
      factors on pathogenesis and progress of type-2 diabetes].
AB  - Onset and progress of several diseases common in adults such as diabetes
      mellitus, hyperlipidemia and hypertension are closely correlated with
      environmental factors. In recent years besides aging, lack of exercise,
      overweight, excess intake of fat and carbohydrates are recognized to be
      increasingly important to develop so called life-style related diseases
      especially in type 2 diabetes. The system of the insulin action from the
      biosynthesis of insulin and excretion in the pancreatic beta cells to receptor
      and insulin signal transmissions is often influenced by unfavorable life style in
      the modernized era. Either for primary or for secondary prevention, education not
      only in patients but in general public must be extensively conducted.

PMID- 10199128
TI  - [Current concept of the pathogenesis of autoimmune type 1 diabetes mellitus].
AB  - In type 1 diabetes, the beta cell is selectively destroyed by T lymphocytes in a
      genetically susceptible individual. Susceptible HLA-class II molecules which have
      low binding affinity with putative beta cell antigens may fail in induction of
      self-tolerance. beta cell-reactive T cells may expand and infiltrate around the
      islet (benign insulitis) by stimulation with environmental factors through
      molecular mimicry and/or beta cell antigens per se. Benign insulitis may develop
      to destructive insulitis under overexpression of Th1 cytokines, which may be
      affected by non-MHC genes. Immune interventions to shift a cytokine balance to
      Th2 dominance in the insulitis lesion may be most realistic approach to suppress
      development of type 1 diabetes after the induction of autoimmunity.

PMID- 10199129
TI  - [Pathogenesis of impaired insulin secretion in NIDDM].
AB  - The most important role of pancreatic beta-cells is the insulin secretion
      responding to the plasma glucose level. Molecular biological and
      electrophysiological approaches have been revealing the molecular mechanism of
      glucose-stimulated insulin secretion. A lot of key molecules of the systems,
      including GLUT2, glucokinase, SUR1, Kir6.2 and CD38, have been cloned and
      characterized whether the mutations in these genes are responsible for the
      pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM). In this paper,
      we summarized the recent advances concerning pathogenesis of NIDDM in respect of
      impaired insulin secretion from pancreatic beta-cells.

PMID- 10199130
TI  - [Molecular mechanism and clinical impact of insulin resistance in type 2 diabetes
      mellitus].
AB  - Type 2 diabetes is characterized by insulin resistance as well as impaired
      insulin secretion. Thus, the enhancement of insulin sensitivity is a possible
      treatment modality. The mechanism of insulin resistance is still unknown.
      However, some genetic backgrounds may be involved and modulated by environmental
      factors. Obesity is considered to be one of major factors to induce insulin
      resistance. Regarding mechanism of obesity-induced insulin resistance, the
      increased expression of Tumor necrosis factor alpha and abnormality in PTPase are
      postulated. Prolonged hyperglycemia also induces the impairment of insulin
      action, resulting in worsening glycemic control. Abnormal glucosamine
      biosynthesis and impaired receptor kinase are considered to be involved in the
      hyperglycemia-induced insulin resistance.

PMID- 10199131
TI  - [NIDDM susceptibility genes].
AB  - Non-insulin dependent diabetes mellitus (NIDDM) is a heterogeneous disorder and
      both genetic and nongenetic factors are associated with the development of
      diabetes. Until now five genes (HNF-4 alpha, glucokinase, HNF-1 alpha, IPF-1 and
      HNF-1 beta), whose mutation can result in MODY, insulin and insulin receptor
      genes, and mitochondria DNA have been reported to be responsible for diabetes.
      Furthermore the mutations in some genes which work for insulin secretion or
      action also have been reported. This review discusses our current knowledge of
      these NIDDM susceptibility genes.

PMID- 10199132
TI  - [New classification of diabetes by ADA and WHO with special reference to
      pathogenesis].
AB  - New classification of diabetes mellitus was proposed by ADA international
      committee on the diagnosis and classification and by WHO consultation committee.
      The classification based on the pathogeneses of diabetes and also on the stages
      of diseases. Since our knowledge on causes of diabetic syndrome is not yet enough
      to classify diabetes in genetic bases, the classification had been carried out
      some sort of mixture of pathogeneses, genetic findings and clinical features of
      hyperglycemia. Stages of diseases based on the natural course of diabetes
      mellitus in reference to shortage of insulin effects and degree of chronic
      hyperglycemia. These two components of classification composed two dimensions of
      the field that expresses all the pathogeneses and metabolic conditions of all
      diabetic patients.

PMID- 10199133
TI  - [Some comments on ADA and WHO reports on the new criteria for the diagnosis of
      diabetes mellitus].
AB  - The Expert Committee of ADA and a WHO working group reported the new criteria for
      the diagnosis of diabetes mellitus in 1997 and 1998, respectively. However,
      similar conclusions were obtained in those separate reports. The main changes
      proposed are as follows. The diagnostic fasting plasma glucose value has been
      lowered to > or = 126 mg/dl. Impaired Glucose Tolerance (IGT) is changed to allow
      for the new fasting level. A new category of Impaired Fasting Glycaemia (IFG) is
      proposed to encompass values which are above normal but below the diagnostic cut
      off for the diabetes (plasma > or = 110 to < 126 mg/dl). It is hoped that the new
      criteria for the diagnosis will be useful in the therapeutic judgements of
      diabetes mellitus.

PMID- 10199134
TI  - [Outline of revision of classification and diagnostic criteria of diabetes
      mellitus in Japan].
AB  - Japan Diabetes Society organized a committee for the revision of diagnostic
      criteria of diabetes mellitus in 1995. Like ADA and WHO reports, this committee
      adopts a classification based on etiologies, and presents a two-dimensional
      figure with etiologies and the state of insulin deficiency on different axis. The
      words IDDM and NIDDM will be retained as terms representing the different degree
      of insulin deficiency. On the basis of glycemia, diabetic type is defined when
      fasting plasma glucose exceeded 126 mg/dl and/or 2-hour plasma glucose by 75 g
      GTT exceeded 200 mg/dl. The diagnosis of diabetes in an individual can be made by
      confirming sustained diabetic type on repeated tests or co-existance of
      characteristic clinical features of diabetes. Normal type is defined by FPG < 110
      mg/dl and 2hPG < 140 mg/dl. The borderline type, defined as neither normal nor
      diabetic types, corresponds to IFG plus IGT according to ADA and WHO reports. The
      application of HbA1c for diagnosis of diabetes and the criteria for gestational
      diabetes mellitus are also discussed.

PMID- 10199135
TI  - [Role of advanced glycation end products (AGE) in the development of diabetic
      microangiopathies and the beneficial effects of AGE inhibitors].
AB  - Glucose or other reducing sugars in plasma or tissue fluids react with proteins
      by a nonenzymatic, post-translational process called glycation or Maillard
      reaction which leads to the formation of advanced glycation end products (AGEs).
      AGEs are implicated in the multiorgan complications of diabetes because of their
      multipotent bioactivities through their receptors as well as the functional and
      structural derangement of the AGE-bearing proteins. AGE inhibitors such as
      aminoguanidine have been shown to have beneficial effects on the progression of a
      full range of diabetic complications in animal models. Furthermore, a recent
      clinical study showed that aminoguanidine therapy resulted in significant
      improvements in several key measurements; it reduced urinary protein, LDL
      cholesterol and triglycerides as well as blood pressure. A novel class of AGE
      antagonists, AGE breakers have been also developed and waiting for the clinical
      evaluation.

PMID- 10199136
TI  - [Vascular endothelial cell dysfunction in diabetes mellitus].
AB  - Diabetes mellitus is complicated with vascular disorders such as atherosclerosis
      (macroangiopathy) and retinopathy (microangiopathy). In macroangiopathy, AGE
      plays an important role in atherogesis through NF-kappa B activation, that
      induces VCAM-1 and MCP-1. Diabetic retinopathy is based on the microangiopathy
      characteristic of angiogenesis. VEGF is a key substance in the angiogenesis in
      the retina. VEGF is produced from retinal cells exposed to AGE, adenosine, bFGF.
      VEGF elictes angiogenesis and increased vascular permeability (retinal edema). I
      consider that AGE is the most important substance in diabetic vascular disorder.
      Therefore, I expect a new application for diabetic angiopathy to suppress the
      effect of AGE.

PMID- 10199137
TI  - [Diabetic neuropathy: clinical and experimental progress in its pathogenesis and
      treatment].
AB  - Diabetic symmetrical polyneuropathy have been known to arise from metabolic
      alteration such as accelerated polyol pathway and/or from neurovascular deficit.
      Recently, two other hypotheses were confirmed. Decreased neurotrophic supports
      were reported in diabetic neuropathy. Subcutaneous injection of recombinant human
      nerve growth factor ameliorated sensory symptoms and cooling detection threshold.
      The most common adverse effect was injection site hyperalagesia. Brain-derived
      neurotrophic factor, neurotrophin-3 and insulin-like growth factors are under
      clinical trials. The excessive oxidative stresses are also associated with
      diabetic neuropathy. Increased production and decreased scavenge system of free
      radicals enhance their cytotoxic effects. Alpha-lipoic acid, gliclazide and
      troglitazone have been reported to be effective for diabetic neuropathy.

PMID- 10199138
TI  - [Diabetic retinopathy--the mechanisms of the ocular neovascularization and the
      development of anti-angiogenic drugs].
AB  - Ocular neovascularization contributes to severe visual loss of the patients with
      diabetic retinopathy (DR) which is the leading cause of blindness on adults of
      working age. The mechanisms of ocular neovascularization are not fully
      understood. Several growth factors, particularly vascular endothelial growth
      factor (VEGF), vasoactive peptides such as angiotensin II and adhesion molecules
      such as integrins are considered to contribute to the ocular neovascularization.
      VEGF is believed to play the key role in the development of DR. Ischemic hypoxia
      of retina is well known to be the potent stimulus for the production of VEGF. In
      addition, we have reported that reactive oxygen intermediates, advanced glycation
      end products and insulin-like growth factor-1, also all, may participate in the
      pathogenesis of DR through their ability to increase VEGF production. The trials
      for anti-angiogenic drugs is developing now for the treatment of DR. VEGF may be
      the most suitable target for the inhibition of the ocular neovascularization.

PMID- 10199139
TI  - [Diabetic nephropathy--recent advances in its mechanism and treatment].
AB  - The elevated glomerular filtration rate that occurs in 25 to 40 percent of
      insulin-dependent diabetics has been proposed as having a role in the initiation
      and evolution of diabetic nephropathy. We report that both enhanced NO synthesis
      by ecNOS in afferent arterioles and glomerular endothelial cells and increased
      expression of IGF-1 receptor can cause glomerular hyperfiltration, and that
      upregulated expression of ICAM-1 can promote the intraglomerular infiltration of
      mononuclear cells, which were prevented by aldose reductase inhibitor. The
      results of United Kingdom Prospective Diabetes Study (UKPDS) will also be
      discussed.

PMID- 10199140
TI  - [Mechanism of atherosclerosis in diabetes: altered cytokine network in the
      vascular wall].
AB  - In the diabetic vascular complication, biochemical and mechanical injuries to
      endothelial cells are involved not only in the process of microangiopathy, but
      also in diabetic atherosclerosis (or arteriosclerosis) which is so-called
      macroangiopathy. In the presence of diabetes or persistent hyperglycemia, many
      cytokines including growth factors such as PDGF, HB-EGF, IL-1 beta and TNF alpha
      are upregulated in intimal cells of the arterial or aortic wall. These changes
      alter the cytokine network in the common mechanism of atherosclerosis, "Response
      to-injury hypothesis", and further accelerate the formation of atherosclerotic
      lesion. In addition, diabetes causes abnormal responsibility to HB-EGF, PDGF and
      TGF-beta in medial smooth muscle cells leading to the elevated activity to their
      proliferation and migration into the intima. Thus, all cell types consisting
      arterial or aortic wall are involved in the process of diabetic atherosclerosis.

PMID- 10199141
TI  - [Slowly progressive IDDM].
AB  - A prospective study over 10 years on the natural history of beta-cell function in
      islet cell antibody (ICA)-positive NIDDM disclosed a characteristic findings of
      slowly progressive IDDM distinct from those of acute onset IDDM. The
      characteristics includes: (1) the clinical phenotype at the onset of diabetes is
      non-insulin requiring, (2) the onset is late age, (3) beta-cell failure
      progresses slowly over several years with persistently positive low-titer ICA and
      high titer of GAD antibodies, (4) pathological study on autopsied pancreas
      demonstrated that beta-cell loss is incomplete, and exocrine pancreas is often
      atrophied with cell infiltration of CD8+ T lymphocytes, (5) higher family history
      of NIDDM, and (6) association with some genetic predisposition including HLA
      DQA1*0301-DQB1*0401 and/or mitochondrial gene mutation at nucleotide pair 3243,
      and a lack of association with HLA-A24. These results are sharply contrast with
      acute onset IDDM, suggesting a presence of distinct subtype of IDDM in Japanese
      population. We also demonstrated that small dose of insulin therapy was effective
      for the suppression of immunological beta-cell failure.

PMID- 10199142
TI  - [Childhood diabetes mellitus].
AB  - Long-term check of 68 type 1 diabetes patients (1978-1998); 23 under age 19, mean
      age 13.4 +/- 4.1 (group A) and 45 above age 20, mean age 26.7 +/- 4.9 (group B)
      were analyzed. 1) Mean onset age were 5.5 +/- 3.9 years old in group A whereas
      7.8 +/- 3.5 in B. 2) In all type 1 diabetes high prevalences of positive HLA-DQ
      region gene and ICA and/or GADA were found. About 11% of all these patients
      showed the clinical pattern of slowly progressive variants. 3) Treatment
      modalities in individuals were successfully selected out of various combinations
      of insulin and multiple daily injection (MDI) styles. 4) Late complication
      prevalences were none in A and very little in B (8.9% background and none
      proliferative retinopathy, 2.2% nephropathy and 2.2% hypertension). 5) Five
      married females were able to have 7 normal babies. Sixteen type 2 diabetes
      patients, including one MODY 2, were successfully treated with combinations of
      sulfonylureas/alphaglucosidase inhibitors/insulin.

PMID- 10199143
TI  - [Syndromes of severe insulin resistance].
AB  - The syndromes of extreme severe insulin resistance are mainly caused by genetic
      defects of the insulin receptor gene (Type A syndrome, Leprechaunism, and Rabson
      Mendenhall syndrome) or by the presence of circulating autoantibodies that
      disrupt the normal functions of the insulin receptor (Type B syndrome). These
      syndromes are characterized by the hyperinsulinemia and severe insulin resistance
      and in most cases accompanied by impaired glucose tolerance and diabetes
      mellitus. The clinical features common to these syndromes are acanthosis
      nigricans, hyperandrogenism and ovarian dysfunction. On the other hand, an
      important distinguishing typical feature in type B syndrome is evidence of other
      autoimmune disorders. [These syndromes can be a contributory causes of insulin
      resistance in a subpopulation with NIDDM.]

PMID- 10199144
TI  - [Syndrome X].
AB  - Insulin resistance is an early and major feature in the development of non
      insulin-dependent diabetes mellitus(NIDDM). It is also associated with
      hyperlipidemia, hypertension, obesity and cardiovascular disease. It is the
      clustor of the risk factors for atherosclerosis and recognized as 'insulin
      resistance syndrome' (Syndrome X). Central (abdominal) obesity is much more
      strongly associated with insulin resistance than overall obesity. The increase of
      both the influx of free fatty acid to liver and the production of TNF-alpha in
      adipose tissue may play an important role in mechanism of insulin resistance
      associated with central obesity. Calorie restriction and weight loss improve
      insulin sensitivity in overweight humans. Exercise training also improves insulin
      sensitivity via increased oxidative enzymes, glucose transporters (GLUT4) and
      capillarity in muscle as well as by reducing abdominal fat. The new 'glitazones'
      (thiazolidinediones) is used clinically to improve insulin sensitivity.

PMID- 10199145
TI  - [Pathogenesis and management of gestational diabetes mellitus].
AB  - The definition of gestational diabetes mellitus (GDM) is carbohydrate intolerance
      of varying degrees of severity, with onset or first recognition during pregnancy.
      GDM develops due to insulin resistance during pregnancy and impaired insulin
      secretion. The problems of GDM are increasing the risk of adverse pregnancy
      outcome and development of diabetes later in life in the mother. To prevent
      adverse perinatal outcome, it is important to screen for glucose intolerance as
      early in pregnancy as possible, and to control maternal hyperglycemia
      intensively. To reduce the risk of future diabetes in the mother, patient should
      control weight and increase physical activity.

PMID- 10199146
TI  - [Diabetes mellitus in the elderly].
AB  - The prevalence of diabetes mellitus and glucose intolerance increases with
      advancing age. Age-related changes in glucose intolerance in non-diabetic
      subjects are primarily observed in postprandial blood glucose levels with only
      small changes in fasting levels. Age-related adjustment in the goals of treatment
      is much more important than that in diagnostic criteria. A careful assessment of
      the current medical status and consideration of remaining life expectancy are
      important in elderly patients with diabetes mellitus. Elderly patients with
      diabetes mellitus can be divided into two subgroups: elderly age-at-onset and
      younger age-at-onset groups. Diabetes in the former category is usually mild
      whereas patients in the latter category often suffer from chronic diabetic
      complications. It is important to assess the current status of patients relative
      to these categories and adjust the treatment of diabetes mellitus relative to
      current medical status of patients.

PMID- 10199147
TI  - [Secondary diabetes].
AB  - Secondary diabetes can be defined as a diabetic condition that develops after the
      destruction of the beta-cells in the pancreatic islets and/or the induction of
      insulin resistance by an acquired disease (e.g. endocrinopathies) or others.
      Recently, diabetes mellitus has divided into four distinct types (type 1
      diabetes, type 2 diabetes, other specific types of diabetes and gestational
      diabetes) in the Report of the Expert Committee on the Diagnosis and
      Classification of Diabetes Mellitus in USA. The categories between secondary
      diabetes and the other specific types of diabetes might be different a little,
      some of the latter being described here. The details of the genetic defects in
      insulin action has been presented elsewhere (see Chapter V-3).

PMID- 10199148
TI  - [Prevention of diabetes mellitus].
AB  - Diabetes mellitus is one of the most common chronic diseases in the developed
      countries and is a major cause of blindness, renal failure or amputations, all of
      which require expensive health-care resources. Diabetes is also associated with
      the increased risk of cardiovascular and cerebrovascular diseases and a
      substantial reduction in life expectancy. Therefore, prevention of diabetes is
      desirable. Recently, epidemiological studies have provided a basis of
      understanding the environmental determinants of diabetes and several prospective
      studies have shown that in the aggregate, intensive therapy improves health-care
      status by improving not only microvascular disease but also macrovascular disease
      in both type 1 and type 2 diabetes.

PMID- 10199149
TI  - [Perspective of dietary management and exercise therapy in diabetes mellitus].
AB  - Diet and exercise are basic measures of treatment of diabetes mellitus. To
      prevent the development and progression of atherosclerotic disease as well as
      microangiopathy, diet management should be focused on the reductions of
      conventional risk factors for atherosclerosis such as hyperglycemia,
      dyslipidemia, and hypertension. To control the these risk factors, both total
      energy and fat intake should be reduced. A diet high in mono- and poly
      unsaturated fatty acids, and dietary fibers are recommended to diabetic patients,
      but the ideal ratio of saturated, monounsaturated, and polyunsaturated fatty
      acids should be determined from clinical and epidemiological studies in the
      future. A high concentration of plasma homocysteine is a new risk factor for
      atherosclerotic disease in diabetic patients. To reduce plasma homocysteine, diet
      enriched in folate and vitamin B12 may be recommended. A high intake of
      flavonoid, one of antioxidants, may be also recommended in diabetic patients
      because of its counteraction against increased oxidative stress in diabetes
      mellitus. Exercise therapy is an effective measure for improving glycemic control
      in Type 2 diabetic patients. However, the most appropriate kinds and strength of
      exercise in diabetic patients with complications or elderly diabetic patients
      still remain unknown. The dietary regimen or exercise of diabetic patients should
      be determined individually according to the risk factors, complications, and
      psychological and socioeconomic conditions.

PMID- 10199150
TI  - [Therapeutic utility of biguanides in the treatment of NIDDM].
AB  - Metformin, one of the biguanides, is an oral hypoglycemic agent which acts
      primarily by decreasing hepatic glucose output and by increasing peripheral
      glucose disposal, therefore it has different hypoglycemic mechanism from that of
      sulfonylureas. The hypoglycemic effects of metformin are observed not only in
      obese NIDDM patients, but also in non-obese NIDDM patients. Moreover, addition of
      metformin improves glycemic control in patients with suboptimal glycemic control
      while taking maximum sulfonylurea therapy. Therefore, it is complementary to
      sulfonylurea therapy and represents a useful additional drug for the treatment,
      irrespective of obesity. The rare but serious condition of lactic acidosis should
      be kept in mind as a potential side effect, however, if metformin is avoided in
      patients with contraindications, the medication is very safe.

PMID- 10199151
TI  - [Use of sulfonylurea (SU) in the treatment of diabetes mellitus].
AB  - The main action of SU in the treatment of diabetes mellitus is the stimulation of
      insulin secretion, and the extrapancreatic action including stimulation of
      insulin actions in glycogen synthesis and inhibition of glucose production in
      liver is also reported. The indication of SU in the treatment of diabetes
      mellitus is for NIDDM usually after diet therapy or suitable exercise therapy. In
      IDDM and several special cases including diabetic ketoacidosis, severe infection,
      pregnancy, poor-controlled NIDDM, gangrane, surgery operation, severe renal or
      hepatic failure et al. insulin therapy should be started. In mild NIDDM,
      gliclazide, tolbutamide or acetohexamide is used, and in more severe NIDDM
      glibenclamide is used. The action time of chlorpropamide is very long, usually
      from 20 to 60 hours, therefore special care should be taken for hypoglycemia. As
      the causes for secondary failure, transition from NIDDM to IDDM, failure of diet
      therapy, glucose toxity and others are considered.

PMID- 10199152
TI  - [alpha-Glucosidase inhibitor].
AB  - Oral anti-diabetic agents with hypoglycemic action via mechanisms distinct from
      the sulfonylureas have recently been developed. One of these, alpha-glucosidase
      inhibitor slows the absorption rate of carbohydrate from the small intestine.
      Effects of voglibose on glycemic control and on the function of pancreatic islets
      were evaluated using Goto-Kakizaki (GK) rats with non-insulin-dependent diabetes
      mellitus (NIDDM). Insulin secretory capacity in response to glucose of islets was
      significantly improved after 8-week administration of voglibose. The treatment
      increased the insulin content of the islets to almost twice that in untreated
      controls. Thus, the treatment can restore the deteriorated islet function of GK
      rats, possibly through protection from glucose toxicity.

PMID- 10199153
TI  - [Insulin-sensitizing agent].
AB  - Troglitazone is a new oral insulin-sensitizing agent from the thiazolidinedione
      group of compounds that has been developed in Japan Thiazolidinediones improve
      the insulin sensitivity at muscle, adipose tissue and liver. The overall
      effectiveness of troglitazone seems to be less potent than is usually seen with
      sulfonylureas, however, there are good responders to troglitazone, in which
      sulfonylurea had failed to improve glycemia. It is frequently very effective for
      those who are very obese and show hyperinsulinemia. Recent reports demonstrate
      the good therapeutic power of troglitazone in combination with a sulfonylurea or
      metformin, or insulin. In future, a possibility that reduction of insulin
      resistance by troglitazone reduce cardiovascular risk will be discussed.
      Unfortunately, wider use has led to recognition of potential for serious liver
      damage. Until now, the mechanisms of the liver toxicity has not been known. We
      have to monitor GOT, GPT and LDH levels as recommended.

PMID- 10199154
TI  - [Indication of intensive insulin therapy and its practice].
AB  - DCCT and Kumamoto Study demonstrated that optimal glycemic control with intensive
      insulin therapy could delay the onset and progression of the early stages of
      diabetic microvascular complications in Japanese patients with noninsulin
      dependent diabetes as well as in patients with insulin dependent diabetes
      mellitus. To obtain optimal glycemic control, the prandial insulin supplements
      before each meal are recommended for insulin requiring patients with noninsulin
      dependent diabetes mellitus whose residual B cell functions are retained to some
      extent, whereas the combined basal at bedtime plus prandial insulin supplements
      are essential for the patients with noninsulin dependent diabetes mellitus whose
      residual B cell functions are severely exhausted as well as in the patients with
      insulin dependent diabetes mellitus. The glycemic threshold to prevent the onset
      and progression of diabetic microvascular complications in the Kumamoto Study was
      indicated as follows; HbA1c < 6.5%, fasting blood glucose concentration < 110
      mg/dl, and 2-hour postprandial blood glucose concentration < 180 mg/dl.

PMID- 10199155
TI  - [Insulin-sensitizing agents].

PMID- 10199156
TI  - [Sulfonylurea drug--a new sulfonylurea drug for type 2 diabetes].
AB  - The incidence of diabetes mellitus has been increased year by year and now 5-6
      millions are diabetic patients in Japan. Studies of DCCT and UKPDS concluded that
      tight control of diabetes was benefit for prevention of diabetic complications in
      type 1 and type 2 diabetes, respectively. New type of sulfonylurea (glimepiride)
      has been developed by Hoechst Marion Roussel company which continues clinical
      trials in Japan. Grimepiride is an insulin sparing sulfonylurea drug for the
      treatment of type 2 diabetes patients whose high blood glucose cannot be
      controlled by diet and exercise alone. In Europe and United State glimepiride has
      been used as a monotherapy or in combination with insulin. Glucose control was
      effectively observed in type 2 diabetics including obese and hypertensive
      patients by the drug. Mechanism of sulfonylurea which stimulates insulin release
      is supposed by binding to a regulatory subunit of plasma membrane ATP-sensitive
      K+ (KATP) channel. The consequent closure of KATP channel leads to
      depolarization, opening of voltage-dependent Ca2+ channels, Ca2+ influx, and a
      rise in intracellular [Ca2+], resulting in insulin secretion. However, it has
      been suggested that sulfonylurea may have an additional action on secretion,
      independent of changes in intracellular [Ca2+] but dependent on the activity of
      protein kinase C (PKC). It is controversial whether or not sulfonylurea is a
      risky drug to the process of diabetic macroangiopathy, by suppressing KATP
      channels in the heart.

PMID- 10199157
TI  - [Non-SU, insulin secretagogues].
AB  - The chemical structures, mechanisms of actions, bioavailabilities,
      insulinotrophic and hypoglycemic actions, and clinical trials of three novel oral
      hypoglycemic agents, NN-623, A-4166 and KAD-1229 are overviewed. They are non-SU
      insulin secretagogues and they induce quicker and shorter hypoglycemia than
      sulphonylureas do, presumably because they are rapidly absorbed into (Tmax: < 30
      min) and excreted from blood (T 1/2: < 60 min). They bind to the SU-receptors and
      suppress K-ATP channels like sulphonylureas do. They stimulate mainly the initial
      phase of insulin release and evoke a decrease in postprandial rises in plasma
      glucose in several animals and humans. Clinical trials demonstrated they are
      efficacious and safe in the treatment of NIDDM subjects. They are useful as a
      first choice drug for the early stage of NIDDM.

PMID- 10199158
TI  - [Rapid-acting insulin analogues].
AB  - Two rapid-acting insulin analogues, Lys(B28), Pro(B29)-human insulin (insulin
      lispro) and Asp(B28)-human insulin (insulin aspart) are developed and introduced
      into the clinical trials or applications recently. The replacement of the natural
      amino acid sequence at the position 28 of the B-chain of human insulin results in
      an insulin molecule with reduced self association. Proline at position B28 near
      the COOH terminal of the B chain of human insulin is important for the
      dimerization of insulin molecules. These two insulin analogues exist in solution
      as a monomeric form and display faster pharmacodynamic action than human regular
      insulin. In healthy volunteers when injected subcutaneously, serum insulin
      concentration peaks more than twice higher and in less than half the time,
      compared to regular insulin. The glucose infusion rate to maintain the euglycemia
      level peaked in about half the time, but the total glucose infused during the
      euglycemic clamp is not significantly different from that of regular insulin.
      These rapid absorbed insulin analogues significantly inhibited the postprandial
      plasma glucose excursion more effectively even injected just before each meal in
      type 1 diabetic patients. The shorter duration of insulin action reduced the risk
      of severe hypoglycemia in nighttime or late postprandial time. The long-term
      treatment with this analogues improved HbA1c levels. Use of these insulin
      analogues as a preprandial bolus injection improves the quality of life of
      insulin-treated patients.

PMID- 10199159
TI  - [Design and development strategy for wearable and implantable artificial
      endocrine pancreas].
AB  - The ultimate goal of development of an artificial endocrine pancreas is for long
      term strict glycemic control, and therefore, the trend in development is now from
      bedside-type to wearable- or implantable-type. With either a miniaturized
      extracorporeal glucose monitoring system based on microdialysis sampling method
      or a ferrocene-mediated needle-type glucose sensor covered with highly
      biocompatible membrane, and with subcutaneous insulin infusion algorithm using
      short-acting insulin analogue, long-term physiological glycemic control could be
      obtained by wearable artificial endocrine pancreas. The next step will be
      directed to the implantable one. Non-invasive infrared absorbance spectroscopy to
      fit into an artificial tooth prosthesis, an implantable artificial endocrine
      pancreas, in which measured glucose concentrations are transmitted telemetrically
      to implanted computer and pump system, might be developed.

PMID- 10199160
TI  - [Current status and future prospect of pancreas and islet transplantation].
AB  - As of November 1997, 9,891 pancreas transplantation were reported to the
      International Pancreas Transplant Registry. In the United States, for all 1994
      97, SPK, PAK, and PTA transplants, one-year graft survival rates were 82%, 71%,
      and 62%, respectively. The 1994-97 pancreas survival rates in all categories were
      higher than in previous eras. The improvement in graft survival rates has been
      associated with the introduction of FK506 and MMF, but excellent results are seen
      with cyclosporine, so the improvement may in part be due to the increasing
      experience that centers now have with pancreas transplantation. Although the
      standard surgical procedure remains pancreas-exocrine bladder drainage, the
      number of enteric drainage cases is increasing. It has been reported that the
      portal venous and enteric drainages are safe, with outcomes similar to those of
      standard technique. It appears that these will become the standard methods in the
      near future. Although 15 pancreas transplantations have been carried out in
      Japan, they ceased after 1994. Currently, social debate to determine the rules
      governing such procedures is ongoing. As of December 1995, 306 adult islet
      allotransplantation were reported to the Islet Transplant Registry. One-year
      islet survival rates were 27% in cases for 1990-94. Islet transplantation has the
      potential to be the most physiological advantage for the treatment of diabetes
      mellitus. However, the endocrine function provided by these transplants has been
      far from optimal.

PMID- 10199161
TI  - [Expression of a novel transcript for the TRH receptor in human pituitary
      adenomas].
AB  - We measured amounts of thyrotropin-releasing hormone receptor (TRHR) mRNA in
      human pituitary tumors, and found a novel transcript of the TRHR gene.
      Competitive PCR revealed expression of the TRHR mRNA in all pituitary adenomas
      examined, and its level was variable and similar to that in the normal pituitary.
      When the C-terminal region was amplified by PCR, an additional short product was
      observed. Cloning and sequence analysis of this short fragment revealed that the
      deleted sequence corresponded exactly to the 5' sequence of exon 3, indicating
      alternative splicing of the TRHR mRNA. This alternative splicing resulted in a
      frame shift yielding a C-terminal truncated protein (HTRHR2) on translation. The
      mRNA ratio of the HTRHR2 versus the wild-type was significantly different among
      pituitary tumors.

PMID- 10199162
TI  - [Calcium-sensing receptor and its related diseases].
AB  - The cloning of a G protein-coupled, extracellular calcium-sensing receptor (CaSR)
      provided direct evidence that Ca(2+)-sensing can occur through receptor-mediated
      activation of G proteins and their associated downstream regulators of cellular
      function. CaSR transcripts and protein are present in various tissues that are
      involved in Ca2+ homeostasis and that do not have well-established roles in Ca
      balance as well. The physiological relevance of the CaSR has been established by
      identifying inherited hyper-and hypocalcemia disorders resulting from CaSR
      mutations: familial hypocalciuric hypercalcemia and neonatal severe
      hyperparathyroidism result from inactivating CaSR mutations while autosomal
      dominant hypocalcemia is caused by activating mutations. CaSR may also play a
      role in water metabolism. Calcimimetics that activate CaSR are undergoing
      clinical trials and might prove effective in manipulation of serum calcium
      concentration and urinary calcium excretion through CaSR activities.

PMID- 10199163
TI  - [A.D. Ado and the development of allergology as a science (1959-1970)].

PMID- 10199164
TI  - [The interaction between neuromediators and immune receptors].

PMID- 10199165
TI  - [Bacterial infection in the etiology of bronchial asthma].
AB  - The role of bacterial infection in etiopathogenesis of bronchial asthma should
      not be underestimated. The use of maintenance instead of causal treatment is not
      valid. We insist on antibiotic therapy and long-term bacterial immunotherapy of
      bronchial asthma and support value of bacterial antigen potentiating the action
      of inhalation antigen. This is confirmed by our treatment results which are very
      good.

PMID- 10199166
TI  - [Increased sensitivity to cockroaches of the species Blattella germanica in
      patients with allergic diseases].
AB  - Sensitization to Blattella germanica (B.g.) was studied in 290 allergic patients
      having increased sensitivity to house dust (HD). The study carried out by ELISA
      techniques with the use of allergen especially developed by the authors, revealed
      that the sera of adults and children with bronchial asthma (BA) contained high
      levels of IgE antibodies (Ab) to B.g. in 34 and 63.5% of cases, respectively. The
      presence of pronounced IgE-linked sensitization of target cells of BA patients
      was confirmed in leukocyte alteration test and in the natural leukocyte migration
      inhibition test. Increased sensitization to B.g. was shown to be the second in
      the total spectrum of sensitization to different arthropod species in house dust,
      and the presence of mixed sensitization to B.g. and HD mites was not due to cross
      reactions caused by main mite allergens. The content of IgG and IgG4 Ab to B.g.
      in BA patients exceeds that in healthy subjects, the tendency towards reverse
      correlation (r = -0.4) between the content of specific IgE and IgG Ab being
      revealed in the former. An essential role of sensitization to cockroaches in
      pathogenesis of BA is emphasized.

PMID- 10199167
TI  - [T-cells as immunomodulation targets: a new strategy in allergy therapy].

PMID- 10199168
TI  - [Chemical modification of allergen leading to changes in its epitopic activity].
AB  - Modification of a model allergen ovalbumin (OA) with succinylation led to a
      decrease of its allergenicity measured by passive cutaneous anaphylaxis reaction,
      RAST inhibition assay and basophil histamine release. Modified OA stimulated OA
      specific T-cell hybrid 3DO-548 to produce IL-2 at the same level as in case of
      non-modified OA. Modified OA did not induce anti-OA IgE, but did induce anti-OA
      IgG antibodies. This approach to chemical modification of allergen-selective
      blockade of B-cell epitopes while not affecting T-cell epitopes suggests new
      opportunities in creation of safe and effective allergovaccines.

PMID- 10199169
TI  - [Immunologic safety of vaccines].

PMID- 10199170
TI  - [The eosinophilic leukocyte as a key cell of inflammation in atopic bronchial
      asthma].

PMID- 10199171
TI  - [Allergy: allergens, induction and IgE synthesis regulation].

PMID- 10199172
TI  - [DOTS strategy and its application in Russia].
AB  - Leading principles of DOTS strategy for Russia are outlined. It has been
      introduced in Russia since 1994 in Ivanovo, Tomsk Regions, Mary El Republic. New
      territories (Leningrad and Arkhangelsk Regions) have recently joined the project.
      Methods of detecting bacillary patients, scheme of chemotherapy for different
      tuberculosis patients and of bacteriological and x-ray follow-up control are
      presented. Positive aspects of the program are analyzed as well as causes of its
      insufficient benefit under conditions of Russian Federation.

PMID- 10199173
TI  - [Results of DOTS use in Russia].
AB  - At present, the DOT programme has been introduced in Russia, which is supported
      by the following foreign organizations: MERLIN (British non-governmental agency;
      WHO, Finnish Association of Pulmonary Diseases; Norwegian Association of Patients
      with Tuberculosis; New York Institute of Health, "Physicians Without Borders"
      (Belgium). The main point of the programme is to identify bacillary patients with
      tuberculosis in the clinical diagnostic laboratories among those who see doctors
      for complaints of suspected tuberculosis. While implementing the programme, the
      work of a general health care laboratory could be activated in identifying
      patients with tuberculosis.

PMID- 10199174
TI  - [Analysis of tuberculosis morbidity in the southeastern district of Moscow].
AB  - The present-day poor epidemiological conditions are marked by an increase in
      tuberculosis detection rates (1.43%) with low coverage (28.0%) of the population
      with preventive fluorographic surveys and a high proportion (39.0%) of young
      patients (aged 18-39 years) among new cases. The shares of advanced and acute
      forms of tuberculosis were 7.2 and 11.4%, respectively. A decay phase was
      detected in 50.6%, 52.6% of patients isolated bacteria. In children, tuberculosis
      morbidity increased by 28.6% mainly among the unregistered extrafamilial
      contacts. Most patients (75.8%) detected upon their referral to the polyclinics
      and general hospitals had a high proportion of extrapulmonary tuberculosis. Thus,
      the above trends of morbidity show its high potential level.

PMID- 10199175
TI  - [Tuberculosis in Russia].
AB  - An unfavorable epidemiological trend in tuberculosis morbidity and mortality has
      been registered in the last decade. The number of newly detected cases and
      mortality in 1997 vs 1991 rose more than 2-fold reaching 73.9 and 16.7 per
      100,000, respectively. The effectiveness of tuberculosis treatment is worsening:
      bacterial discharge stopped in 72.6%, destruction cavities in the lungs closed in
      62.6%, clinical recovery was obtained in 17.2% of patients (relevant statistics
      for 1986 were 89.9, 81.6 and 21.9%, respectively). To correct the situation,
      government of the Russian Federation has adopted the program of tuberculosis
      control for 1998-2004. The Health Administration of the Ivanovo and Tomsk Regions
      has successfully introduced the DOTS program. Now, this positive experience is
      applied in other regions and institutions.

PMID- 10199176
TI  - [New principles of clinical and X-ray examination of children and adolescents
      registered in special antituberculous hospitals].
AB  - The authors have analyzed informative value of the main clinical and X-ray
      examinations, their scope and frequency in respect to age, tuberculosis stage and
      the disease pattern for children and adolescents on follow-up after treatment in
      special antituberculosis hospitals. A differential scheme of examination of
      followed-up tuberculous children and adolescent has been proposed which raises
      efficacy and cost of the follow-up, minimize exposure to X-rays.

PMID- 10199177
TI  - [Causes of tuberculosis in successfully BCG vaccinated infants and preschool
      children].
AB  - Tuberculosis has developed in 21.5% of infants and preschool children effectively
      vaccinated with BCG. 85.1% of them had uncomplicated and mild forms of the
      disease. The onset of tuberculosis in the vaccinated children was explained
      primarily by poor prophylactic measures among population as a whole and in the
      risk groups, unsatisfactory search for sources of the infection.

PMID- 10199178
TI  - [Diagnosis, clinical picture and treatment policy in acute progressive forms of
      pulmonary tuberculosis under present-day epidemiological conditions].
AB  - Among 103 examinees, the most common clinical type was caseous pneumonia (45.6%),
      progressive fibrocavernous tuberculosis (20.4%), infiltrative caseous pneumonia
      (17.5%), disseminated tuberculosis (16.5%). Progression was characterized by
      cavern formation in 91.1% of patients, with large and giant caverns containing
      nonspecific microbes forming in 79.6%. All the patients were found to isolate
      bacteria and 93.5% showed their excess. Drug-resistant microbes were identified
      in 62.1% of patients; polydrug resistance was seen in 37.5%. Chemotherapy was
      performed at the first stage by using 5 drugs: isoniazid, rifampicin,
      pyrazinamide, ethambutol plus kanamycin or amikacin. A combination of reserve
      drugs, including prothionamide, ofloxacin (ciprofloxacin) amikacin, pyrazinamide,
      and ethambutol, was used in patients with polyresistance. Symptomatic and
      pathogenetic therapies should aim at correcting complications and concomitant
      abnormalities. Following 6 months, 80% of patients stopped isolating bacteria,
      the process became stable and they could be prepared for planned surgical
      treatment. In 20% of cases, the process was progressive and it required salvage
      operations.

PMID- 10199179
TI  - [Current characteristics of advanced and rapidly progressive forms of pulmonary
      tuberculosis].
AB  - Tuberculosis morbidity and mortality in the Moldova Republic has deteriorated
      since 1991. The percentage of advanced and rapidly progressive forms of the
      disease rose 2-3-fold. Most of the patients are 21-50-year-old unemployed men
      living in poor financial and social conditions. Advanced and rapidly progressive
      tuberculosis forms present clinically with multiple symptoms and destructions,
      high incidence of generalized dissemination and involvement of the brain.
      Treatment effectiveness depends on feasibility of combined therapy incorporating
      4-5 antituberculous drugs. After the treatment, 84.1% of the patients stopped
      bacterial discharge, closure of the caverns was achieved in 55.3% of the
      patients.

PMID- 10199180
TI  - [Results of polyresistant tuberculosis treatment: data of the Santarishkes
      Republican tuberculous hospital].
AB  - In 1994-1996 the Santarishkes republican tuberculous hospital (Lithuania) has
      admitted 98 patients (82 males, 16 females) with polyresistant tuberculosis (M.
      tuberculosis were resistant to at least isoniazid and rifampicin). Of these, 13
      patients were untreated, 17 had recurrences, 68 had chronic tuberculosis. After
      polyresistance of M. tuberculosis was found, the patients received an individual
      treatment with sensitive drugs. 20 patients were operated. The absence of
      bacteria was achieved only in 24 (24.5%) patients. Tuberculous lesions in the
      lungs disappeared and clinical symptoms relieved in 14 of them. In 74(75.5%)
      nonresponders the course of the disease was unfavourable. Negative treatment
      outcomes were observed in 38.5%, 64.7% and 85.3% of new-onset, recurrent and
      chronic cases, respectively.

PMID- 10199181
TI  - Caseous and infiltrative-caseous pneumonia in computed tomography.
AB  - Computer tomography (CT) imaging was made in 22 patients with acute tuberculosis-
      caseous and infiltrative-caseous pneumonia. CT role in detection of caseous
      changes, assessment of the extent and structure of caseosis, in differentiation
      of caseous and infiltrative-caseous pneumonia is described. CT is suggested to be
      an optimal roentgenological method of identifying caseous-pneumonic forms of
      tuberculosis.

PMID- 10199182
TI  - [Role of bronchospasm in development of bronchial obstruction in pulmonary
      tuberculosis].
AB  - The examination of 90 patients suffering from pulmonary tuberculosis with
      bronchial obstruction (BO) has found bronchospasm in one third of the examinees.
      In spite of the spasm weakness, its contribution to development of BO is
      significant: 21-40, 41-80, 81-100% in 4, 6 and 27% of patients.

PMID- 10199183
TI  - [Surgical treatment of renal tuberculosis].
AB  - The analysis of the results of surgical treatment of 178 patients with
      destructive nephrotuberculosis indicates that operative methods are justified in
      the treatment of nephrotuberculosis as they provide cleansing of the infection
      focus, restoration of renal and urinary tract function, help to avoid long-term
      and massive chemotherapy. Organ-preserving and reconstructive operations on the
      kidneys and urinary tracts in early disease.

PMID- 10199184
TI  - [Ultrasonic diagnosis of pleurisy in patients with pulmonary tuberculosis].
AB  - Ultrasound proved helpful in diagnosis of pleurisy in tuberculous patients. It is
      able to localize exudate, to determine its volume, size and characteristic
      features as well as to show structure of the pleural layers, the existence of
      pleural adhesions. Echography differentiates changes in the adjacent pulmonary
      tissue and pleura though it is difficult in patients with rapidly progressive
      tuberculosis, especially in caseous pneumonia because affected pulmonary tissue
      is also hypoechogenic. Ultrasound is superior to X-ray in low volumes of the
      liquid in the pleural cavity or atypical position of the pleural exudate.
      Ultrasonic investigation is also used in dynamic control of treatment
      effectiveness without radiation load on the patient.

PMID- 10199185
TI  - [Perspective of tuberculous coxarthrosis sequela endoprosthesis].
AB  - The paper analyzes total endoprosthesis of the hip joint due to tuberculous
      coxitis sequelae in 54 patients. Two patients underwent bilateral endoprosthesis.
      Histological findings confirmed the tuberculous etiology of prior coxitis and
      provided the policy of pre- and postoperative antituberculous therapy. The
      supportability and function of the joint recovered 3-4 months after surgery.
      Arthralgia occurred in 2 patients 4 and 5 years following surgery. In sequelae of
      tuberculous coxitis, hip joint endoprosthesis by the procedure developed in the
      clinic yielded good results.

PMID- 10199186
TI  - [Clinical presentation, course and treatment of recurrent sarcoidosis: followup
      data].
AB  - The paper presents the results of long-term follow-ups of 107 patients with
      recurrent sarcoidosis registered as having Group VII-IB. In the patients, there
      was the greatest dissemination of the process in the lung, intrathoracic lymph
      nodes and other organs and MF MB in the blood, sputum, BAC? Group VIIIB patients
      need the greatest attention of physicians, treatment involving extracorporeal and
      physiotherapeutical methods to prevent respiratory failure and disability.

PMID- 10199187
TI  - [Biochemical mechanisms of thoracic fibrosis development after pneumonectomy in
      patients operated for progressive pulmonary tuberculosis].
AB  - Forty three patients undergone pulmonectomy/pleuropulmonectomy were studied 1-3
      days to 1.5 months after surgery. The content of total protein (TP), fibronectin
      (FN), medium-weight molecules, fibrinogen and fibrin degradation products (FFDP).
      In the absence of complications within the first 3 weeks after surgery, exudate
      was concentrated along with intensive cavitary proteolytic clearance, then there
      was deposited fibrin lysis concurrently with increased local FN synthesis. The
      magnitude of the two latter processes was directly relate to the rates of
      residual cavitary fragmentation and obliteration. In patients with empyema, fluid
      drainage from the residual cavity and exudate was impaired in the early
      postoperative period and the exudate was characterized by very low concentrations
      of TP, FN, FFDP. Subsequently, the phenomena of exudate dilution remained, which
      was associate with a decrease in the rate of proteolytic processes and a slow
      increase in local FN synthesis.

PMID- 10199188
TI  - [Bacteremia in tuberculosis and other mycobacterial infections].

PMID- 10199189
TI  - [Impact of ozonized sorbent hemocarboperfusion on kallikrein-kinin system in
      patients with progressive pulmonary tuberculosis].
AB  - The impact of ozonized sorbent hemocarboperfusion on the kallicrein-kinin system
      (KKS) was studied in 21 patients with slowly progressive (Group 1) and acute
      (Group 2) pulmonary tuberculosis. In Group 1 patients, the baseline values of KKS
      were suggestive of its depression with an increase in alpha 1-protease inhibitor
      (alpha 1-PI). In Group 2 patients, the activity of kallikrein was twice higher
      than the mean normal values with increased uptake of its precursor, a dramatic
      decrease in the level of alpha 2-macroglobulin and an acute phasic elevation of
      alpha 1-PI.

PMID- 10199190
TI  - [Antimycobacterial antigens in lung secretion].
AB  - A latex antibody diagnostic kit was used to reveal microbacterial antigens in the
      sputum of patients with tuberculous and nonspecific lung disease in 54 and 38% of
      cases, respectively. It is suggested that Mycobacterium antigens are present in
      different tissues of an infected macroorganism.

PMID- 10199191
TI  - [Examining fibrotic process in lung during treatment of chronic murine
      tuberculosis with lysosomotropic drug isonaizid].
AB  - Light and ultrastructural morphometries were used to evaluate the effects of
      dextran-conjugated isoniazid (MW 30-40 kDa) on the morphology of chronic
      pulmonary tuberculous inflammation induced by BCG vaccine in mice. The revealed
      antifibrotic effect of the conjugated drug is accompanied by much less damage to
      the alveolar macrophageal ultrastructures (the mitochondrial apparatus in
      particular) than that of free isoniazid. It is concluded that the lysosomotropic
      properties imparted to isoniazid basically change its effect on fibrogenesis and
      are essential in the prevention of antiinflammatory pneumoscleroses.

PMID- 10199192
TI  - [Pulmonary hemorrhage in patients with tuberculosis (lecture)].

PMID- 10199193
TI  - [Clinics in disseminated intravascular coagulation].

PMID- 10199194
TI  - [Genetic polymorphisms and thrombotic disorder].

PMID- 10199195
TI  - [Acute myelogenous leukemia in elderly].

PMID- 10199196
TI  - [Current concept of hemophagocytic syndrome].

PMID- 10199197
TI  - [Diagnosis and pathogenesis of primary (familial) hemophagocytic
      lymphohistiocytosis].

PMID- 10199198
TI  - [Treatment of familial hemophagocytic lymphohistiocytosis].

PMID- 10199199
TI  - [Characteristics of hemophagocytic lymphohistiocytosis in childhood in Japan].

PMID- 10199200
TI  - [Clinicopathological characteristics of adult patients with lymphoma-associated
      hemophagocytic syndrome in Japan].

PMID- 10199201
TI  - [Hemophagocytic syndrome in autoimmune disease].

PMID- 10199202
TI  - [Pathogenesis of hemophagocytic syndrome (HPS)--regarding cytokine].

PMID- 10199203
TI  - [Treatment for adult hemophagocytic syndrome].

PMID- 10199204
TI  - [Storage iron decrease rates and their clinical significance in iron deficiency
      anemia patients following intravenous iron therapy].
AB  - A simple method was devised for determination of the storage iron decrease rate
      (SID) and the number of days to a recurrent state of iron deficiency. Several
      patients with iron deficiency anemia were given intravenous doses of iron, and
      their serum ferritin levels were periodically assayed. A serum ferritin decrease
      curve was plotted semi-logarithmically; back-extrapolation of that curve yielded
      the period of days (D) from the starting day of iron supplement therapy to the
      day by which serum ferritin had decreased to 12 ug/l. The amount of administered
      iron that was initially stored and eventually lost during period D was calculated
      by subtracting the amount of iron utilized for hemoglobin increase (R) from the
      total amount of iron administered (T) to each patient. R was calculated from
      values for patient body weight and change in hemoglobin concentration prior to
      and after therapy. SID values were obtained from the following formula: SID = (T
      R)/mg/day. SID rates and the number of days to a state of recurrent iron
      deficiency were measured in 12 patients. SID rates ranged from 0.8 to 9.8 mg/day,
      and were larger in those patients who exhibited heavier blood loss. A correlation
      was observed between SID values and the half-times for serum ferritin decrease,
      as expressed by the equation, Y = 248.5X0.129 (r = 0.129). SID values reflected
      the negative iron balance of each patient. That observation suggested it should
      be possible to select a more appropriate intravenous iron does for individual
      patients if their SID values are taken into full account.

PMID- 10199205
TI  - [Acute promyelocytic leukemia with t(11;17)(q23;q21)].
AB  - We report the first Japanese case of acute promyelocytic leukemia with
      t(11;17)(q23;q21) and CD56. A 41-year-old man with schizophrenia was hospitalized
      because of the appearance of blasts with Auer bodies in his peripheral blood. A
      bone marrow smear showed an abundance of abnormal cells with scanty azurophile
      granules in the cytoplasm and somewhat lobulated nuclei. Because the abnormal
      cells demonstrated strongly positive peroxidase reactivity with a few faggot
      bodies, the patient was given a diagnosis of acute promyelocytic leukemia (M3v
      according to the FAB classification). However, chromosome analysis revealed
      t(11;17)(23; q21). All-trans retinoic acid (ATRA) was not effective. Mitoxantrone
      was more effective than daunorubicin, and resulted in a complete remission with a
      normal karyotype. About 9 months later, the patient suffered a relapse. Surface
      marker analysis demonstrated blasts that were positive for CD56, CD13, and CD33.
      MEC (mitoxantrone, etoposide, cytarabine) therapy was ineffective. Although ATRA
      was administered at a dose of 80 mg/day for more than 2 months, the number of
      myelocytes and promyelocytes increased Finally CAG (cytarabine, aclarubicin, G
      CSF) therapy was initiated, but the patient died due to intracranial invasion and
      hemorrhage accompanied by disseminated intravascular coagulation.

PMID- 10199206
TI  - [Primary splenic lymphoma with hypoplastic bone marrow].
AB  - A 44-year-old man was admitted because of persistent fever and pancytopenia.
      Because his bone marrow was hypoplastic and the karyotype of his marrow cells was
      normal, he was given a diagnosis of aplastic anemia, and treated with
      glucocorticoids and granulocyte colony-stimulating factor. Splenomegaly was later
      found and a splenectomy performed: pathological findings on resected tissue
      specimens disclosed non-Hodgkin's lymphoma, B-cell diffuse large. The patient was
      transferred to our hospital, where a bone marrow biopsy revealed lymphoma cells
      infiltrating his hypoplastic marrow. Complex chromosomal abnormalities were
      detected in marrow cells, but no lymphadenopathy was observed. A diagnosis of
      primary splenic lymphoma with infiltration of lymphoma cells into bone marrow was
      made, and chemotherapy was accordingly started. After multiple cycles of
      chemotherapy, the patient's marrow recovered to a normal state and his karyotype
      abnormalities disappeared. Six months later, pancytopenia reappeared and lymphoma
      cells were again detected in the patient's bone marrow. We reasoned that the
      hypoplastic state of his bone marrow was associated with the lymphoma, and that
      cytokines, including interferon-gamma, may have been responsible for this
      association.

PMID- 10199207
TI  - [Atypical chronic myeloid leukemia presenting with trilineage dysplasia and IgG
      (lambda) type monoclonal gammopathy].
AB  - A 78-year-old man was diagnosed as leukocytosis in February 1994. Physical
      examination revealed marked hepatosplenomegaly. A peripheral blood examination
      disclosed 95,090/microliter leukocytes without hiatus leukemicus, 6.5 g/dl Hb,
      and 15.0 x 10(4)/microliter platelets. The neutrophil alkaline phosphatase score
      was 27, and serum VB12 was above 1,600pg/ml. IgG was identified as monoclonal
      immunoglobulin of type lambda. Bone marrow specimens demonstrated marked
      granulocytic hyperplasia. Neither the Philadelphia chromosome (Ph1) nor BCR gene
      rearrangement was detected; hence, the diagnosis of Ph1 (-) chronic myeloid
      leukemia (CML) was made. The patient was treated with hydroxyurea and low-dose VP
      16 with no improvement, and died of pneumonia and sepsis in June 1995. This case
      was considered to be consistent with atypical CML (aCML) according to the FAB
      classification because monocytosis was not observed. It seems likely and
      interesting that the coexistent monoclonal gammopathy and aCML might have arisen
      from common abnormal hematopoietic stem cells.

PMID- 10199208
TI  - [Multiple myeloma in siblings].
AB  - We encountered 2 patients with multiple myeloma in a family with 11 siblings,
      suggesting that the occurrence of the disease may be associated with genetic
      factors. Patient 1: The second daughter (age 79) was given a diagnosis of
      multiple myeloma and admitted to our hospital in December 1997 for treatment. IgG
      lambda type M protein was detected by serum immunoelectrophoresis, punched out
      lesions (+) by X ray examination, and atypical plasma cells (14% of total) by
      bone marrow examination. Patient 2: The fifth daughter (age 68) received a
      diagnosis of multiple myeloma and was admitted to our hospital in May 1997 for
      treatment. Bence Jones-kappa type and IgA-kappa type M protein were detected by
      serum immunoelectrophoresis, punched out lesions (+) by X ray examination, and
      atypical plasma cells (90% of total) by bone marrow examination. It was noted
      that the sixth daughter had leukemia; hence, 3 of the 11 siblings had blood
      disorders. For this reason, HLA studies were performed and detected A31, B39,
      B51, and Cw7 in patient 1 and A31, B51, B62, and Cw4 in patient 2. Further case
      studies will hopefully reveal more details concerning the relationship between
      myeloma and HLA.

PMID- 10199209
TI  - [Burkitt's lymphoma originating in gluteal muscle tissue].
AB  - We report a case of Burkitt's lymphoma originating in gluteal muscle tissue. A 61
      year-old Japanese man was admitted to our hospital due to painful swelling of the
      left femur and gluteal region in October 1996. A laboratory examination disclosed
      elevated levels of serum lactate dehydrogenase and soluble interleukin 2
      receptor. Gallium scintigraphy demonstrated accumulations in the left femur and
      gluteal region. Magnetic resonance imaging yielded intense signals and disclosed
      swelling of muscle tissue in the same region. Pathological examination of biopsy
      specimens from the left femur revealed a starry-sky pattern, and a chromosomal
      analysis revealed t(2;8)(p11;q24). Heightened concentrations of antibody for
      Epstein-Barr virus were not detected. Non-African type Burkitt's lymphoma was
      diagnosed on the basis of these findings. CHOP therapy and irradiation of the
      affected region were initially effective, but the disease eventually became
      resistant to treatment. The patient died of cerebral hemorrhage. As far as we
      know, this is the first report in Japan of Burkitt's lymphoma originating in
      muscle tissue.

PMID- 10199210
TI  - [Human parvovirus B19-induced aplastic crisis in a patient treated with fibrin
      sealant].
AB  - A 42-year-old woman underwent a myomectomy on March 31, 1998. On the 10th
      postoperative day, leukopenia and reticulocytopenia were observed. Bone marrow
      aspiration revealed severe erythroblastopenia with giant proerythroblasts,
      suggesting a recent parvovirus infection. Both anti-parvovirus B19 IgM antibody
      and IgG antibody seroconversion was observed, and human parvovirus B19 DNA was
      detected by polymerase chain reaction (PCR) methods. The hematologic data on the
      patient rapidly improved thereafter. It was determined that acute-phase serum had
      inhibited CFU-E and BFU-E derived colony formation. Based on these findings,
      parvovirus B19-induced aplastic crisis was diagnosed. Fibrin sealant, which is a
      typical hemostatic agent produced from blood, had been during the operation.
      Human parvovirus B19 DNA was detected in the fibrin sealant by PCR. Our case
      report documents the transmission of human parvovirus B19 by fibrin sealant.

PMID- 10199211
TI  - [Rapidly progressive irradiated cervical cancer that metastasized to the liver
      during therapy for idiopathic thrombocytopenic purpura].
AB  - A 37-year-old woman was given a diagnosis of cervical cancer in August 1994.
      Because of severe thrombocytopenia, she was given radiation therapy at 50 Gy with
      great effectiveness. The thrombocytopenia was diagnosed as idiopathic
      thrombocytopenic purpura. Because the patient refused to undergo a splenectomy
      operation, she was treated with prednisolone, gamma-globulin, and danazol with no
      effect. In January 1995 she began receiving azathioprine and her platelet count
      gradually increased. In March, she complained of severe left abdominal pain but
      abdominal computed tomography (CT) scans showed no abnormal findings.
      Nonetheless, the patient's lumbago persisted and her liver dysfunction was
      progressive. Abdominal CT scans performed on April 18 disclosed multiple liver
      tumors. The patient died on April 28. Autopsy revealed that the cervical cancer
      was the primary origin of the liver tumors. We concluded that extra precautions
      should be taken when administering immunosuppressive therapy to patients with a
      history of malignant diseases.

PMID- 10199212
TI  - [What is your diagnosis? WPW syndrome].

PMID- 10199213
TI  - [Treatment of adult acute lymphoblastic leukemia].
AB  - In patients with adult ALL, substantial progress has been made in the past 20
      years. At present a cure rate of 30-40% can be achieved and varies in defined
      subgroups between 10-51%. ALL does not represent an uniform disease but is formed
      by biologic subentities, which differ in their natural history, clinical
      presentation and prognosis. A comprehensive diagnostic examination, including
      morphology, cytochemistry, immunology, cytogenetic and molecular genetic analysis
      is a precondition for prognostic assessment and therapeutic stratification. The
      basic principle of ALL treatment is a combination chemotherapy with sequential
      administration of induction, consolidation and maintenance therapy. Bone marrow
      transplantation has become an important part of the treatment strategy and is
      performed in patients with high risk. In the subgroup of T-ALL a significant
      progress has been made in the last years with survival rates of 40-50%. In B-ALL
      the results have been greatly improved to 48-51% by introduction of a specific
      treatment strategy. However, the results (about 30%) stagnate for the total group
      of B-lineage-ALL (common ALL, pre-B-ALL, pro-B-ALL). Patients with B-lineage-ALL
      can be subdivided in a high and low risk group according to the presence of risk
      factors (age, white blood cell count, time to achieve a complete remission, pro-B
      ALL and the translocations t[4;11], t[9;22]). The outcome of the subgroup of
      adult pro-B-ALL has been substantially improved (50%). An increase of treatment
      results (20%) appears in outlines for patients above 50 years. The Ph/bcr-abl
      positive ALL has in spite of improved complete remission rates (60-70%)
      consistently unfavourable survival rates (10%).

PMID- 10199214
TI  - [Acute myeloid leukemia (AML)].
AB  - Acute myeloid leukemia (AML) appears related to some environmental factors and
      higher age. The morphological subtypes reflect genotypes as detected by specific
      chromosome translocations and related fusion genes. Genotypes determine the
      disease biology and prognosis. Chemotherapy remains as the backbone of treatment
      and has brought the long-term disease-free survival to 30-40%. Factors
      contributing to the improved results are prolonged maintenance, double induction
      strategy and high dose AraC in postremission and induction phase. Allogeneic bone
      marrow transplantation adds to the improvements by the graft versus leukemia
      effect. Autologous stem cell transplantations may allow further escalation of
      postremission chemotherapy and might thus further improve the cure rate in AML.

PMID- 10199215
TI  - [Role of aggressive treatment strategies for myelodysplastic syndromes].
AB  - Myelodysplastic syndromes (MDS) constitute a heterogenous group of acquired bone
      marrow disorders characterized by ineffective hematopoiesis, cellular dysfunction
      and an increased risk of transformation into acute myeloid leukemia (AML). The
      percentage of medullary blast cells and the karyotype at diagnosis are the most
      important predictors of survival. Patients with more than 10% blast cells or an
      unfavourable karyotype (chromosome 7 abnormalities or complex aberrations)
      usually survive less than 12 months. This review article focuses on the roles of
      intensive AML-type chemotherapy, autologous stem cell transplantation and
      allogeneic bone marrow transplantation in the management of patients with
      advanced MDS. Recent studies suggest that, with appropriate selection of
      patients, intensive chemotherapy produces high rates of complete remission.
      Chances of entering remission are particularly high in patients with a good
      Karnofsky score, bone marrow blast count < 30% and normal karyotype. When
      compared with acute myeloid leukemia, results of autologous bone marrow
      transplantation in MDS are disappointing. A major disadvantage of this approach
      is the delayed recovery of hematopoiesis. Autologous peripheral blood progenitor
      cell transplantation overcomes this difficulty and is currently explored as
      consolidation therapy after successful remission induction with polychemotherapy
      in an intergroup study of the EORTC and EBMT. Allogeneic bone marrow
      transplantation remains the treatment of choice for younger MDS patients,
      offering a good chance of cure if the transplantation is performed at an early
      stage of disease or if the patient receives the transplant in complete remission
      after conventional chemotherapy.

PMID- 10199216
TI  - [Trachelodynia and unusual muscle ache. The first symptoms in an acute peripheral
      polyneuropathy patient: a 37 year old physician's assistant. Guillain-Barr'e
      syndrome with leg sensorimotor tetraparesis, infectious mononucleosis and low
      grade hepatitis].

PMID- 10199217
TI  - Taking time seriously. A theory of socioemotional selectivity.
AB  - Socioemotional selectivity theory claims that the perception of time plays a
      fundamental role in the selection and pursuit of social goals. According to the
      theory, social motives fall into 1 of 2 general categories--those related to the
      acquisition of knowledge and those related to the regulation of emotion. When
      time is perceived as open-ended, knowledge-related goals are prioritized. In
      contrast, when time is perceived as limited, emotional goals assume primacy. The
      inextricable association between time left in life and chronological age ensures
      age-related differences in social goals. Nonetheless, the authors show that the
      perception of time is malleable, and social goals change in both younger and
      older people when time constraints are imposed. The authors argue that time
      perception is integral to human motivation and suggest potential implications for
      multiple subdisciplines and research interests in social, developmental,
      cultural, cognitive, and clinical psychology.

PMID- 10199218
TI  - The seven sins of memory. Insights from psychology and cognitive neuroscience.
AB  - Though often reliable, human memory is also fallible. This article examines how
      and why memory can get us into trouble. It is suggested that memory's misdeeds
      can be classified into 7 basic "sins": transience, absentmindedness, blocking,
      misattribution, suggestibility, bias, and persistence. The first three sins
      involve different types of forgetting, the next three refer to different types of
      distortions, and the final sin concerns intrusive recollections that are
      difficult to forget. Evidence is reviewed concerning each of the 7 sins from
      relevant sectors of psychology (cognitive, social, and clinical) and from
      cognitive neuroscience studies that include patients with focal brain damage or
      make use of recently developed neuroimaging techniques. Although the 7 sins may
      appear to reflect flaws in system design, it is argued instead that they are by
      products of otherwise adaptive features of memory.

PMID- 10199219
TI  - Reducing sexual transmission of HIV from those who know they are infected: the
      need for personal and collective responsibility.

PMID- 10199220
TI  - Selection of HIV-1 genotypes by cultivation in different primary cells.
AB  - OBJECTIVES: To determine the representation of particular HIV-1 genotypes during
      cultivation in different primary cell-culture systems compared with the spectrum
      of the quasispecies in vivo. METHODS: Primary isolates of HIV-1 were recovered by
      isolation in cultures of lymphocytes, mixed mononuclear cells (MNC), and
      monocytes/macrophages. Nucleotide sequence determination of the C2-V3 region of
      gp120 of HIV was performed on 10-20 independently isolated clones derived by
      polymerase chain reaction from the culture systems, the uncultured peripheral
      blood MNC (PBMC) as well as plasma. RESULTS: Several predominant HIV genotypes
      were found in the uncultured PBMC from each of the patients. The most frequent
      genotypes in PBMC were also the most frequent types in plasma. In addition,
      lymphocytes, macrophages or mixed MNC cultures allowed the outgrowth of variants
      that were underrepresented in uncultured PBMC. We showed that the virus
      cultivation systems used in this study selected differently for the genetic
      variants. Whereas some genotypes were present in all three culture systems,
      although at different frequencies, others were exclusively found in a specific
      culture system. CONCLUSIONS: These results demonstrate that monocyte/macrophage
      and mixed MNC culture systems complement the standard lymphocyte culture in terms
      of the spectrum of genotypically different virus variants obtained in vitro.

PMID- 10199221
TI  - Nitric oxide synthase expression and apoptotic cell death in brains of AIDS and
      AIDS dementia patients.
AB  - OBJECTIVES: To determine the occurrence and cellular localization of inducible
      nitric oxide synthase (iNOS), NOS activity and its association with cell death in
      brains of AIDS and AIDS dementia complex (ADC) patients. DESIGN AND METHODS: Post
      mortem cerebral cortex tissue of eight AIDS patients, eight ADC patients and
      eight control subjects was processed for iNOS immunocytochemistry, NADPH
      diaphorase activity staining as an index of NOS activity, and in situ end
      labelling to detect cell death. RESULTS: iNOS-positive cells were present in the
      white matter of 14 out of 16 AIDS and ADC patients, whereas two out of eight
      control subjects showed iNOS-positive cells. iNOS immunoreactivity was
      exclusively localized in activated macrophages and microglial cells that both
      showed NADPH-diaphorase activity. In addition, NADPH-diaphorase activity, not
      related to iNOS immunoreactivity, was observed in astrocytes in both white and
      grey matter of AIDS and ADC patients. All AIDS and ADC patients, and only one
      control subject showed characteristic features of apoptotic cell death.
      CONCLUSIONS: Different forms of NOS are present in microglial cells and
      astrocytes of AIDS and ADC patients but are largely absent in control subjects.
      Although more NOS-expressing cells occur in ADC than in AIDS patients, apoptotic
      cell death was found in both patient groups to the same extent. We postulate that
      NO production in brains of AIDS patients results in cumulative cortical cell
      loss, which becomes neurologically evident at later stages of disease and is
      expressed as ADC.

PMID- 10199222
TI  - Increased interleukin-10 in the the endocervical secretions of women with non
      ulcerative sexually transmitted diseases: a mechanism for enhanced HIV-1
      transmission?
AB  - OBJECTIVE: Although non-ulcerative sexually transmitted diseases (STD) and
      bacterial vaginosis are implicated as cofactors in heterosexual HIV-1
      transmission, the mechanisms have not been defined. Recent in vitro data suggest
      that interleukin (IL)-10 may increase susceptibility of macrophages to HIV-1
      infection. Therefore, we performed this study to assess whether non-ulcerative
      STD are associated with detection of IL-10 in the female genital tract. METHODS:
      Women with clinical pelvic inflammatory disease with or without cervicovaginal
      discharge were recruited from an STD clinic in Nairobi, Kenya. Endocervical and
      endometrial specimens were obtained for Neisseria gonorrhoeae and Chlamydia
      trachomatis DNA detection, Trichonomas vaginalis culture, and CD4 and CD8 T-cell
      enumeration. Bacterial vaginosis was diagnosed by Gram stain. IL-10 was detected
      in endocervical specimens using enzyme-linked immunosorbent assay. Blood was
      obtained for HIV-1 serology. RESULTS: One hundred and seventy-two women were
      studied. N. gonorrhoeae, C. trachomatis, bacterial vaginosis, and T. vaginalis
      were detected in 38 (21%), 17 (9%), 71 (43%), and 22 (12%) women, respectively.
      Cervical IL-10 was detected more often in women with N. gonorrhoeae [adjusted
      odds ratio (AOR), 3.4; 95% confidence interval (CI), 1.4-8.4], C. trachomatis
      (AOR, 4.4; 95% CI, 1.2-15.6), and bacterial vaginosis (AOR, 3.1; 95% CI, 1.4-6.9)
      than in women without these infections. CONCLUSIONS: The association of non
      ulcerative STD and bacterial vaginosis with increased frequency of IL-10
      detection in endocervical secretions suggests a potential mechanism through which
      these infections may alter susceptibility to HIV-1 infection in women.

PMID- 10199223
TI  - HIV-1 infectivity and host range modification by cathepsin D present in human
      vaginal secretions.
AB  - OBJECTIVE: To investigate HIV-1 infectivity in the natural environment of vaginal
      secretions. DESIGN: Vaginal wash samples collected from 14 healthy women were
      incubated in vitro with various HIV-1 strains for 10 min at 37 degrees C and then
      assayed for infectivity on primary lymphocyte cultures, or on CEM cells, or on
      CD4- ME180 cells derived from vaginal epithelium. METHODS: HIV-1 infectivity was
      measured by early virus growth in the various host cells tested using a
      quantitative p24 assay and by the Karber procedure. RESULTS: Preincubation of HIV
      1(IIIB) with vaginal wash samples or 2 microg/ml cathepsin D increased the
      ability of the virus to grow in lymphocyte cultures. The vaginal wash effect was
      abolished by 5 microg/ml pepstatin A, an inhibitor of aspartyl proteases.
      Presence of precursor and mature forms of cathepsin D in vaginal wash was
      demonstrated after passage through a pepstatin A-agarose column. Median tissue
      culture infective doses of HIV-1(IIIB) and HIV-1(JRFL) strains were increased
      14.4-fold and 18-fold, respectively, after preincubation in vaginal wash sample,
      and were increased by pretreatment with 2 microg/ml cathepsin D. When CD4
      receptors of CEMss cells were blocked by OKT4a monoclonal antibody, the cells
      lost susceptibility to HIV-1 (IIIB), but supported the growth of virus pretreated
      with vaginal wash sample or cathepsin D. These treated viruses were able to
      initiate infection of CD4-ME180 epithelial cells, which were not receptive to
      untreated virus. ME180 cells were shown to possess the messenger of CXC-chemokine
      receptor-4. CONCLUSIONS: Vaginal secretions may help HIV-1 transmission to women
      by increasing infectivity for CD4+ cells and allowing entrance into some CD4
      epithelial cells.

PMID- 10199224
TI  - Prognostic value of plasma HIV RNA in the natural history of Pneumocystis carinii
      pneumonia, cytomegalovirus and Mycobacterium avium complex. Multicenter AIDS
      Cohort Study.
AB  - OBJECTIVES: To use follow-up on untreated HIV-positive men to assess the
      prognostic information provided by baseline data on plasma HIV RNA, CD4 cell
      count, age, and HIV-related symptom status, separately for three specific AIDS
      defining illnesses: Pneumocystis carinii pneumonia (PCP), cytomegalovirus (CMV),
      and Mycobacterium avium complex (MAC). METHODS: The study population were 734 HIV
      positive homosexual men enrolled in the Multicenter AIDS Cohort Study, with
      follow-up (1984-1985 through mid-1988) restricted to the antiretroviral treatment
      free and prophylaxis-free era. Baseline marker values were categorized and
      assessed as predictor variables in separate time-to-event analyses for each of
      the three specific outcomes. RESULTS: A total of 138 cases of PCP, 25 cases of
      CMV, and 25 cases of MAC were observed. For PCP and CMV, higher categories of HIV
      RNA and lower categories of CD4 cell count were associated with increased risk
      relative to the respective reference groups. For MAC, oral candidiasis or fever
      and elevated HIV RNA at baseline were the primary risk factors. Further analysis
      highlighted the importance of monitoring HIV RNA levels in addition to CD4 cell
      counts when evaluating patients' risk of developing PCP. CONCLUSIONS: In the
      absence of treatment, plasma HIV RNA levels provide prognostic information about
      the risk of these three specific AIDS-defining illnesses, independently of the
      CD4 cell count. These data provide a useful reference as researchers investigate
      changing patterns in the incidence and predictors of opportunistic infections in
      the era of increasingly active antiretroviral therapies.

PMID- 10199225
TI  - A stochastic model for primary HIV infection: optimal timing of therapy.
AB  - OBJECTIVE: To investigate the optimal time point for the initiation of therapy in
      HIV infection from the perspective of drug resistance. BACKGROUND: The enormous
      genetic diversity of HIV within an infected individual represents one of the
      greatest challenges for effective therapy, because the viral population may
      harbour drug-resistant mutants that rapidly outgrow the wild-type virus once the
      patient starts treatment. To determine the optimal timing of therapy it is
      crucial to know how long it takes for the viral population to build up sufficient
      diversity to enable the virus to escape from therapy. METHOD: A stochastic model
      of the viral diversification during primary infection was used to study the
      behaviour of small population sizes of mutant virus. RESULTS AND CONCLUSIONS: The
      simulations suggest that from the perspective of viral diversity, therapy should
      be started at the viral set-point. Starting treatment earlier involves a risk of
      the selective outgrowth of drug-resistant mutants, which are transiently present
      at the viral peak during primary infection.

PMID- 10199226
TI  - Clinical cross-resistance between the HIV-1 protease inhibitors saquinavir and
      indinavir and correlations with genotypic mutations.
AB  - OBJECTIVES: To determine the clinical efficacy of the HIV-1 protease inhibitor
      indinavir (IDV) in saquinavir (SQV)-experienced patients and delineate the
      developing drug-resistance patterns. DESIGN: Open-label prospective clinical
      trial. SETTING: University hospital research center. PATIENTS: Ten patients who
      had completed a SQV monotherapy study in which they had received SQV at a dose of
      3600 or 7200 mg daily (two and fourfold the standard dose). INTERVENTIONS: At
      enrollment patients received IDV for 4 weeks as monotherapy, after which
      zidovudine (ZDV) and lamivudine (3TC) were added to their drug regimen. Patients
      then received combination therapy (IDV-ZDV-3TC) for an additional 20 weeks to
      complete a total of 24 weeks of therapy. MAIN OUTCOME MEASURES: Plasma HIV RNA
      viral load and CD4+ T-cell counts were monitored. Sequencing of the HIV protease
      gene was performed to determine the development of resistance mutations. Plasma
      samples for sequencing were taken before initial SQV therapy, after SQV therapy
      before starting IDV, and after 24 weeks of IDV therapy. RESULTS: The average
      duration of high-dose SQV before starting IDV was 58+/-29.2 weeks. A 0.58 log10
      RNA copies/ml increase was noted during the 3-week washout phase followed by a
      mean reduction in plasma HIV RNA viral load of 1.2 log10 RNA copies/ml after 4
      weeks of IDV. After the addition of ZDV and 3TC at week 4, HIV RNA continued to
      fall reaching a mean reduction of 1.96 log10 RNA copies/ml at week 24. Plasma HIV
      RNA was below 400 RNA copies/ml in six out of nine patients at week 24. CD4+ T
      cell counts showed a gradual rise from 328 x 10(6)/l to 453 x 10(6)/l by week 24.
      SQV therapy had resulted in multiple mutations in the protease gene. Six of the
      patients had developed five or more mutations: L90M in two, G48V in four (of
      which three also contained L101), and V82A in three. Patients in whom plasma HIV
      RNA was not durably suppressed by subsequent IDV combination therapy developed
      multiple (up to four) additional mutations within 24 weeks, including codons 54,
      82 and 93 amongst others. No clear correlation was found between the mutations
      that had developed in individual patients after SQV and the subsequent efficacy
      of IDV. CONCLUSION: Prolonged use of SQV at potent doses in the presence of
      elevated viral load levels resulted in the development of multiple resistance
      mutations. Individual resistance patterns varied greatly between patients, as did
      their virological response to therapy. Resistance assays may be useful in
      identifying which patients will benefit from salvage therapy with a second
      protease inhibitor.

PMID- 10199227
TI  - Virological response to protease inhibitor therapy in an HIV clinic cohort.
AB  - OBJECTIVE: New antiretroviral strategies aim to reduce plasma HIV RNA (viral
      load) to below the limits of detectability of assays with the objective of
      reducing viral replication in order to stop or reverse the pathogenic process and
      prevent development of drug resistance. First use of a protease inhibitor might
      offer the most realistic chance of achieving this aim. Our objective was to study
      the virological response to protease inhibitors in patients taking them for the
      first time. METHODS: A total of 901 patients from a large outpatient clinic were
      followed a mean of 15 months from the time of starting a protease inhibitor until
      1 May 1998. Viral load and CD4 cell count measurements were made on average every
      34 days. RESULTS: Overall there was a 79% [95% confidence interval (CI), 76-82]
      probability of the patients achieving a viral load < 500 copies/ml by 24 weeks
      after starting the protease inhibitor. In a multiple Cox regression model, those
      with lower initial viral load [relative hazard (RH), 0.72; P < 0.0001], higher
      CD4 cell count (RH, 1.07; P = 0.002), those starting other new drugs at same time
      as the protease inhibitor (RH, 1.46 for two versus none; P = 0.003), those who
      were antiretroviral-naive, and those using indinavir or nelfinavir were more
      likely to achieve such levels. In those 651 patients achieving viral load < 500
      copies/ml within 24 weeks, there was an estimated 53% (95% CI, 51-55) probability
      of rebound of viral load to > 500 copies/ml by 52 weeks from the first
      undetectable value. Again, those who had started other new drugs at the same time
      as the protease inhibitor (RH, 0.57; P = 0.003 for starting two versus none)
      tended to experience a lower probability of viral load rebound, as did those with
      higher initial CD4 cell count (RH, 0.87 per 100 x 10(6)/l higher; P = 0.0007).
      Those who took saquinavir achieved less durable virological responses than those
      who took other protease inhibitors. CONCLUSIONS: Starting protease inhibitor
      therapy with two other new antiretroviral drugs simultaneously with protease
      inhibitor therapy offers a better best chance of achieving sustained viral load <
      500 copies/ml than starting fewer new drugs.

PMID- 10199228
TI  - Bone marrow macrophage iron grade and survival of HIV-seropositive patients.
AB  - OBJECTIVE: Increased iron stores predispose to certain microbial infections. This
      association might be especially important in patients whose immune system is
      impaired by HIV. This study examined the relationship between iron stores and the
      survival times of patients with HIV infection. DESIGN: Retrospective analysis of
      iron stores, as determined directly in bone marrow aspirates, and of hospital
      records. SETTING: The George Washington University Hospital, an urban academic
      tertiary care institution. PATIENTS: Three hundred and forty-eight HIV
      seropositive adults who had diagnostic bone marrow aspirates between January 1985
      and June 1996. MEASUREMENTS: Bone marrow macrophage iron stores were graded on a
      scale of 0 to 5. For analysis of the influence of iron stores on survival, we
      compared patients with grades 4-5 iron stores (markedly or massively increased; n
      = 188) to those with grades 0-2 iron stores (normal or decreased; n = 130).
      RESULTS: Infections caused by Candida spp., Pneumocystis carinii, and
      Mycobacterium spp. were more common in patients with high macrophage iron grades
      than in patients with low or normal iron grades (P < or = 0.006). The adjusted
      estimated rate of death (hazards ratio) was higher in patients with high iron
      stores compared with patients with low or normal iron stores, both from the time
      of the bone marrow study (ratio of 2.1; 95% confidence interval 1.3-3.5; P =
      0.003) and the determination of HIV-seropositivity (ratio of 2.8; 95% confidence
      interval 1.4-4.9; P = 0.001). CONCLUSION: High iron stores, as determined by bone
      marrow macrophage iron grade, may be associated with shorter survival times in
      patients with HIV infection.

PMID- 10199229
TI  - Evaluation of the World Health Organization staging system for HIV infection and
      disease in Ethiopia: association between clinical stages and laboratory markers.
AB  - OBJECTIVE: To study the association between the clinical axis of the World Health
      Organization (WHO) staging system of HIV infection and disease and laboratory
      markers in HIV-infected Ethiopians. DESIGN: Cross-sectional study. METHODS:
      Clinical manifestations and stage of HIV-positive individuals participating in a
      cohort study of HIV infection progression, and of HIV-positive patients
      hospitalized with suspicion of AIDS, were compared to CD4+ T-cell count and viral
      load. RESULTS: Of the 86 HIV-positive participants of the cohort study, 53 (62%),
      16 (19%), 16 (19%), and one (1.2%) were in stage 1, 2, 3 and 4, respectively.
      Minor weight loss (n = 15) and pulmonary tuberculosis (n = 9) were the most
      commonly diagnosed conditions among the 38 (44%) symptomatic HIV-positive
      individuals. Although 23 (27%) HIV-positive participants had CD4+ T-cell counts
      less than 200 x 10(6)/l, only one was in clinical stage 4. Among 79 hospitalized
      HIV-positive patients, 15 (19%) and 64 (81%) were in stage 3 and 4, respectively.
      The majority (83.5%) had CD4+ T-cell counts < 200 x 10(6)/l. Individuals at stage
      3 had lower CD4+ T-cell counts and higher viral loads when seen in hospital as
      compared to cohort participants (P = 0.06 and 0.008, respectively). When grouping
      the two study populations, the median CD4+ T-cell count decreased (337, 262, 225,
      126, and 78 x 10(6)/l, P< 0.01), and the median viral load increased (4.08, 3.89,
      4.47, 5.65, and 5.65 log10 copies/ml, P < 0.01), with increasing clinical stage
      of HIV infection (1, 2, 3 cohort, 3 hospital, and 4, respectively). Median CD4+ T
      cell counts were remarkably low in HIV-negative participants (749 x 10(6)/l), and
      in HIV-positive participants at stage 1 and 2 (337 and 262 x 10(6)/l,
      respectively). CONCLUSIONS: There was a good correlation between WHO clinical
      stages and biological markers. CD4+ T-cell counts were low in Ethiopians,
      particularly during early stages of HIV-1 infection, and preliminary reference
      values at different stages of HIV-1 infection were determined. In HIV-infected
      Ethiopians, lymphocyte counts less than 1,000 x 10(6)/l in non-hospitalized
      individuals, and less than 2,000 x 10(6)/l in hospitalized patients, had high
      positive predictive value, but low sensitivity, in identifying subjects with low
      CD4+ T-cell counts (< 200 x 10(6)/l) who would benefit from chemoprophylaxis of
      opportunistic infections. The on-going longitudinal study will be useful to
      confirm the prognostic value of the WHO staging system.

PMID- 10199230
TI  - Reductions in risk behaviour provide the most consistent explanation for
      declining HIV-1 prevalence in Uganda.
AB  - OBJECTIVE: To monitor the HIV-1 epidemic in Western Uganda and the possible
      impact of interventions. DESIGN: Results from sentinel surveillance of HIV-1
      seroprevalence were compared with cross-sectional serosurvey data and model
      simulations. METHODS: Age-specific trends in HIV-1 prevalence between 1991 and
      1997 amongst antenatal clinic (ANC) attenders in the town of Fort Portal, where a
      comprehensive AIDS control programme has been implemented since 1991, were
      analysed. Results were compared with outputs from a mathematical model simulating
      the HIV-1 epidemic in Uganda. Two scenarios were modelled: one without and one
      with behaviour change. Sentinel surveillance data were compared with data from a
      population-based HIV-1 serosurvey at the study site, which was carried out in
      early 1995. RESULTS: Data from 3271 ANC attenders identified greater education
      and being single as risk factors for HIV-1 infection. A significant decrease of
      risk for women with secondary school education over time was observed, whereas
      the risk for illiterate women remained high. Among women aged 15-19 years (n =
      1045) education and marital status-adjusted HIV-1 prevalence declined steadily
      from 32.2% in 1991 to 10.3% in 1997. For 20-24-year-old women (n = 1010) HIV-1
      prevalence increased until 1993 from 19.9% to 31.7% and decreased thereafter
      (21.7% in 1997). These trends closely follow the prediction of the model
      simulation assuming behaviour change, and for 1995-1997, confidence intervals of
      the HIV-1 prevalence estimate exclude the model output for an uninfluenced
      epidemic. No clear trends of HIV-1 prevalence were found in older women (n =
      1216) and comparisons with the model were ambiguous. Sentinel surveillance data
      at the time of the population survey closely reflected results for the female
      general population sample for the two younger age-groups (15-19 and 20-24 years).
      In contrast, pregnant women aged 25-29 years showed significantly lower rates
      than the population sample (20.8% versus 45.1%). CONCLUSION: HIV-1 prevalence
      amongst ANC attenders aged 15-24 years can be used to monitor the HIV-1 epidemic
      in the given setting. Declining trends of HIV-1 prevalence in women aged 15-19
      and 20-24 years most likely correspond to a reduced HIV-1 incidence attributable
      to changes in behaviour. Our data also show that sentinel surveillance data need
      to be age-stratified to give useful information.

PMID- 10199231
TI  - Age of male circumcision and risk of prevalent HIV infection in rural Uganda.
AB  - OBJECTIVE: To assess whether circumcision performed on postpubertal men affords
      the same level of protection from HIV-1 acquisition as circumcisions earlier in
      childhood. DESIGN: Cross-sectional study of a population-based cohort. SETTING:
      Rakai district, rural Uganda. METHODS: A total of 6821 men aged 15-59 years were
      surveyed and venous blood samples were tested for HIV-1 and syphilis. Age at
      circumcision was dichotomized into men who were circumcised before or at age 12
      years (prepubertal) and men circumcised after age 12 years (postpubertal).
      Postpubertal circumcised men were also subdivided into those reporting
      circumcision at ages 13-20 years and > or = 21 years. RESULTS: HIV-1 prevalence
      was 14.1% in uncircumcised men, compared with 16.2% for men circumcised at age >
      or = 21 years, 10.0% for men circumcised at age 13-20 years, and 6.9% in men
      circumcised at age < or = 12 years. On bivariate analysis, lower prevalence of
      HIV-1 associated with prepubertal circumcision was observed in all age,
      education, ethnic and religious groups. Multivariate adjusted odds ratio of
      prevalent HIV-1 infection associated with prepubertal circumcision was 0.39 [95%
      confidence interval (CI), 0.29-0.53]. In the postpubertal group, the adjusted
      odds ratio for men circumcised at ages 13-20 years was 0.46 (95% CI, 0.28-0.77),
      and 0.78 (95% CI, 0.43-1.43) for men circumcised after age 20 years. CONCLUSIONS:
      Prepubertal circumcision is associated with reduced HIV risk, whereas
      circumcision after age 20 years is not significantly protective against HIV-1
      infection. Age at circumcision and reasons for circumcision need to be considered
      in future studies of circumcision and HIV risk.

PMID- 10199232
TI  - Maternal viral load and timing of mother-to-child HIV transmission, Bangkok,
      Thailand. Bangkok Collaborative Perinatal HIV Transmission Study Group.
AB  - OBJECTIVES: To determine the proportion of HIV-1-infected infants infected in
      utero and intrapartum, the relationship between transmission risk factors and
      time of transmission, and the population-attributable fractions for maternal
      viral load. DESIGN: Prospective cohort study of 218 formula-fed infants of HIV-1
      infected untreated mothers with known infection outcome and a birth HIV-1
      positive DNA PCR test result. METHODS: Transmission in utero was presumed to have
      occurred if the birth sample (within 72 h of birth) was HIV-1-positive by PCR;
      intrapartum transmission was presumed if the birth sample tested negative and a
      later sample was HIV-1-positive. Two comparisons were carried out for selected
      risk factors for mother-to-child transmission: infants infected in utero versus
      all infants with a HIV-1-negative birth PCR test result, and infants infected
      intrapartum versus uninfected infants. RESULTS: Of 49 infected infants with an
      HIV-1 birth PCR result, 12 (24.5%) [95% confidence interval (CI), 14 -38] were
      presumed to have been infected in utero and 37 (75.5%) were presumed to have been
      infected intrapartum. The estimated absolute overall transmission rate was 22.5%;
      this comprised 5.5% (95% CI, 3-9) in utero transmission and 18% (95% CI, 13-24)
      intrapartum transmission. Intrapartum transmission accounted for 75.5% of
      infections. High maternal HIV-1 viral load (> median) was a strong risk factor
      for both in utero [adjusted odds ratio (AOR) 5.8 (95% CI, 1.4-38.8] and
      intrapartum transmission (AOR, 4.4; 95% CI, 1.9-11.2). Low birth-weight was
      associated with in utero transmission, whereas low maternal natural killer cell
      and CD4(+) T-lymphocyte percentages were associated with intrapartum
      transmission. The population-attributable fraction for intrapartum transmission
      associated with viral load > 10 000 copies/ml was 69%. CONCLUSIONS: Our results
      provide further evidence that most perinatal HIV-1 transmission occurs during
      labor and delivery, and that risk factors may differ according to time of
      transmission. Interventions to reduce maternal viral load should be effective in
      reducing both in utero and intrapartum transmission.

PMID- 10199233
TI  - The impact of potent antiretroviral therapy on the characteristics of
      hospitalized patients with HIV infection.
AB  - OBJECTIVE: Despite advances in antiretroviral treatment, a large number of HIV
      infected patients still require hospitalization. This study describes the
      characteristics of HIV patients requiring hospitalization before and after the
      advent of potent antiretroviral therapies. METHODS: Information was collected on
      all HIV-positive patients admitted to the New York Hospital-Cornell Medical
      Center in New York City. Data was collected from 1 January through 30 June 1995,
      and during the same 6-month interval in 1997. RESULTS: In each time period over
      1500 outpatients were receiving treatment for HIV infection. There was a
      significant decrease in the incidence of admission [60.4 per 100 patient-years
      (PY) in 1995, 28.8 per 100 PY in 1997], and length of stay (10 versus 8 days).
      The median CD4 cell count of all HIV-infected patients admitted to the hospital
      doubled: 37 x 10(6)/l in 1995 versus 80 x 10(6)/l in 1997. However, there was no
      significant change in the median CD4 cell count of patients diagnosed with
      opportunistic infections. The incidence of the most common diagnosis (bacterial
      pneumonia, 8.0 per 100 PY in 1995 versus 3.6 per 100 PY in 1997) and the most
      common opportunistic infection (Pneumocystis carinii pneumonia 7.6 per 100 PY in
      1995 versus 2.4 per 100 PY in 1997) decreased significantly. CONCLUSIONS: Since
      the introduction of potent antiretroviral therapy, a significant decrease in the
      incidence of hospital admission and opportunistic infections has occurred. There
      has been a doubling of the median CD4 cell count of inpatients. There has been no
      significant change in the median CD4 cell count at which patients present with
      opportunistic infections.

PMID- 10199234
TI  - Evidence for cdc2 gene in pneumocystis carinii hominis and its implication for
      culture.

PMID- 10199235
TI  - High frequency of the 3'A mutation of the SDF-1 gene in Cambodia.

PMID- 10199236
TI  - Alleles that may influence HIV-1 pathogenesis in Chinese subjects.

PMID- 10199237
TI  - Role of highly active antiretroviral therapy in human papillomavirus-induced
      genital dysplasia in HIV-1-infected patients.

PMID- 10199238
TI  - Host protein incorporation is conserved among diverse HIV-1 subtypes.

PMID- 10199239
TI  - Reversal of accelerated neutrophil apoptosis and restoration of respiratory burst
      activity with r-metHuG-CSF (Filgrastim therapy in patients with AIDS.

PMID- 10199240
TI  - Why are the decay rates in plasma HIV-1 different for different treatments and in
      different patient populations?

PMID- 10199241
TI  - Patients with HIV-1 RNA below 1000 copies/ml after 48 weeks on dual nucleoside
      combination therapy. Delta Coordinating Committee.

PMID- 10199242
TI  - Kaposi's sarcoma is an important risk factor for survival in HIV-infected
      patients independent of CD4+ cell count.

PMID- 10199243
TI  - An HIV-1-infected individual homozygous for the CCR-5 delta32 allele and the SDF
      1 3'A allele.

PMID- 10199244
TI  - Risk factors for adjacent-segment failure following lumbar fixation with rigid
      instrumentation for degenerative instability.
AB  - OBJECT: The authors performed a retrospective analysis of 125 consecutive
      patients in whom instrumentation was placed to promote lumbar fusion for the
      treatment of degenerative instability. All procedures were performed by a single
      surgeon. The authors sought to determine the risk factors for next-segment
      degeneration after lumbar spinal fusion with rigid instrumentation. METHODS:
      Thirty-one of 125 fusion procedures were performed in women who were
      postmenopausal. A total of 18 of 125 patients developed symptomatic next-segment
      degeneration at a previously asymptomatic level; 15 were postmenopausal women.
      Data were obtained in patients with next-segment failure based on radiographic
      studies, neurological assessment, demographic factors, and sequential follow-up
      examinations. The mean follow-up period for this group was 44.8 months. All women
      were postmenopausal, and 53% received biphosphonate drugs and calcium
      supplementation preoperatively for osteopenia. Twenty percent of all patients
      with next-segment failure were cigarette smokers. Next-segment diseases included
      spondylolisthesis (39%), spinal canal stenosis due to disc herniation and/or
      facet hypertrophy (33%), stress fracture of the adjacent vertebral body (28%),
      and scoliosis (17%). Patients frequently had more than one degenerative process
      at the next segment. CONCLUSIONS: The risk of adjacent-segment failure is clearly
      higher for patients in whom lumbar fusion with rigid instrumentation is performed
      to treat degenerative instability. This risk appears to be especially high in
      postmenopausal women.

PMID- 10199245
TI  - Modified open-door laminoplasty for treatment of neurological deficits in younger
      patients with congenital spinal stenosis: analysis of clinical and radiographic
      data.
AB  - OBJECT: Multilevel anterior cervical decompressive surgery and fusion effectively
      treats cervical myeloradiculopathy that is caused by severe cervical spinal
      stenosis, but degenerative changes at adjacent vertebral levels frequently result
      in long-term morbidity. The authors performed a modified open-door laminoplasty
      procedure in which allograft bone and titanium miniplates were used to treat
      cervical myeloradiculopathy in younger patients with congenital canal stenosis
      while maintaining functional cervical motion segments. Pre- and postoperative
      magnetic resonance imaging and/or computerized tomography myelography were
      performed to assess changes in cervical spinal canal dimensions. Pre- and
      postoperative flexion-extension radiographs were compared to determine the
      residual motion of the targeted operative segments. METHODS: Twenty younger
      patients (average age 37.7 years) underwent modified open-door laminoplasty for
      treatment of myelopathy or myeloradiculopathy related to significant cervical
      spinal stenosis with or without associated central or lateral disc herniation or
      foraminal stenosis. These surgeries were performed during a 2-year period and
      follow-up review remains ongoing (average follow-up period 21.6 months).
      Reconstructive procedures were performed on an average of 4.1 levels (range three
      six). Operative time averaged 186 minutes (range 93-229 minutes). Average blood
      loss was 305 ml (range 100-650 ml). No cases were complicated by neurological
      deterioration, infection, wound breakdown, graft displacement, or hardware
      failure. The patients' Nurick Scale grade improved from a preoperative average of
      1.8 to a postoperative average of 0.5. Pre- and postoperative sagittal spinal
      diameter averaged 11.2 mm (8-14 mm) and 16.6 mm (13-19 mm), respectively. The
      sagittal compression ratio (sagittal/lateral x 100%) increased from 48% pre- to
      72% postoperatively. The spinal canal area increased an average of 55% (range 19
      127%). In patients in whom pre- and postoperative flexion-extension radiographs
      were obtained, 72.7% residual neck motion was maintained. No patient developed
      increased neck or shoulder pain. Neurological symptoms improved in all patients,
      with total relief of myelopathy in 50% and partial improvement in 50%.
      CONCLUSIONS: Modified open-door laminoplasty with allograft bone and titanium
      miniplates effectively treats neurological deficits in younger patients with
      congenital and spinal stenosis. Although long-term results are unknown, short
      term results are good and there is a low incidence of complications.

PMID- 10199246
TI  - Treatment of cervical compressive myelopathy with a new dorsolateral
      decompressive procedure.
AB  - OBJECT: A new dorsolateral decompressive procedure involving a unilateral
      approach has been devised for the treatment of cervical compressive myelopathy.
      In this operation, the posterior spinal elements of the contralateral side are
      not disturbed, and thus, postoperative deformity of the cervical spine can be
      avoided. Following decompressive surgery via the unilateral approach, the
      cervical spine was kept more stable compared with the results obtained after wide
      laminectomy or other expansive laminoplasty procedures. METHODS: Twenty-six
      patients underwent dorsolateral decompressive surgery, and the patients' clinical
      and radiological results were examined during the follow-up period to evaluate
      neurological function and postoperative deformities of the cervical spine. The
      underlying conditions for myelopathy were cervical spondylosis (19 patients),
      ossification of posterior longitudinal ligament (three patients), and
      ossification of yellow ligament (four patients). The follow-up period ranged from
      6 to 110 months (average 35.5 months). Functional recovery, which was rated by
      using the Japanese Orthopaedic Association scoring system, was an average of 56%
      in all patients (100% being equal to full recovery). The recovery rate was
      compatible with those attained after other expansive laminoplasty procedures.
      Radiographically, progression to swan-neck or kyphotic deformity was not observed
      in any patient. No postoperative spinal instability was noted. Based on
      computerized tomography myelograph evaluation, the average transectional area of
      the dural tube at the C4-5 level was expanded from 122 mm2 to 169 mm2, and the
      transectional area of the spinal cord at the C4-5 level was expanded from 39.6
      mm2 to 52.9 mm2 after surgery. CONCLUSIONS: The authors conclude that this
      operative procedure could be used as a new option for the treatment of cervical
      compressive myelopathy.

PMID- 10199247
TI  - Cervical laminectomy without fusion in patients with rheumatoid arthritis.
AB  - OBJECT: The authors performed a prospective study to determine whether cervical
      laminectomy without simultaneous fusion results in spinal instability. METHODS:
      Because of clinical and radiographic signs of cord compression, 15 patients with
      rheumatoid arthritis (including one with Bechterew's disease) and severe
      involvement of the cervical spine underwent decompressive laminectomy without
      fusion performed on one or more levels. Preoperative flexion-extension
      radiographs demonstrated dislocation but no signs of instability at the level of
      cord compression. Clinical and radiological reexamination were performed twice at
      a median of 15 months (6-24 months) and 43 months (28-72 months) postoperatively.
      One patient developed severe vertical translocation 28 months after undergoing a
      C-1 laminectomy, which led to sudden tetraplegia. She required reoperation in
      which posterior fusion was performed. No signs of additional instability at the
      operated levels were found in the remaining 14 patients. In three patients
      increased but stable dislocation was demonstrated. The results of clinical
      examination were favorable in most patients, with improvement of neurological
      symptoms and less pain. CONCLUSIONS: The authors conclude that decompressive
      laminectomy in which the facet joints are preserved can be performed in the
      rheumatoid arthritis-affected cervical spine in selected patients in whom signs
      of cord compression are demonstrated, but in whom radiographic and preoperative
      signs of instability are not. Performing a simultaneous fusion procedure does not
      always appear necessary. Vertical translocation must be detected early, and if
      present, a C-1 laminectomy should be followed by occipitocervical fusion.

PMID- 10199248
TI  - A prospective randomized double-blind controlled trial to evaluate the efficacy
      of an analgesic epidural paste following lumbar decompressive surgery.
AB  - OBJECT: Pain control can often be improved by local (as opposed to systemic)
      application of analgesic and/or anesthetic medication. The purpose of this study
      was to evaluate the efficacy of a single-dose epidural analgesic "paste" in the
      control of postoperative pain in patients who have undergone lumbar decompressive
      surgery. METHODS: Sixty patients undergoing routine elective lumbar decompressive
      surgery were randomized in a double-blind fashion to one of two groups: those
      receiving active paste or placebo paste. The paste was applied to the exposed
      dura at the time of surgery, just prior to wound closure. Patients received
      follow-up care in the hospital and at home for 3 months postsurgery. Several
      outcome measures were studied to ascertain differences in pain control and to
      ensure comparability between groups. Patients who received active paste
      demonstrated significantly lower pain scores compared with those who received
      placebo paste for up to 6 weeks postoperatively. General health perception
      indexed by the Short Form 36 was also significantly better in patients who
      received active paste for up to 6 weeks. In-hospital and outpatient oral narcotic
      consumption was significantly lower in the active paste-treated group. Inpatient
      straight leg raising scores were improved in those patients who received active
      compared with control paste. CONCLUSIONS: Application of an analgesic paste
      directly to the epidural space during lumbar decompressive surgery significantly
      improves postoperative pain control, reduces prescribed analgesic drug
      consumption, and improves overall health perception for up to 6 weeks following
      surgery. The authors conclude that this postoperative pain control strategy is
      both effective and safe and may provide a new standard of pain management in
      patients undergoing lumbar discectomy or laminectomy.

PMID- 10199249
TI  - Results of the surgical treatment of perimedullary arteriovenous fistulas with
      special reference to embolization.
AB  - OBJECT: This retrospective study was performed to evaluate the results of
      surgical treatment and the use of preoperative embolization in managing patients
      with perimedullary arteriovenous fistulas (AVFs). METHODS: The authors studied 20
      consecutive patients with perimedullary AVFs who underwent surgical treatment.
      Arteriovenous shunts were at the level of the cervical spine in five patients,
      the thoracic spine in 12, and the conus medullaris in three patients. Of the 20
      AVFs, three were fed by the anterior spinal artery only, three by the posterior
      spinal artery, and 14 by both the anterior and posterior spinal arteries. Nine
      patients had varices that compressed the spinal cord. Eleven patients underwent
      surgery, and nine patients underwent surgery combined with adjuvant preoperative
      embolization. Preoperative embolization remarkably reduced blood flow through the
      AVFs and facilitated subsequent surgical procedures. Postoperative angiography
      revealed complete disappearance of the AVFs in 16 patients. However, small
      fistulas persisted in the other four patients, whose large lesions were fed by
      the anterior spinal artery. Postoperatively, neurological status was improved in
      11 patients, unchanged in eight, and worse in one patient. CONCLUSIONS: Effective
      interruption of a spinal arteriovenous shunt was achieved by surgery in all
      cases, even when the anterior spinal artery was involved. For large and high-flow
      AVFs, embolization proved to be a useful adjunct to surgery.

PMID- 10199250
TI  - Variations of the extreme-lateral craniocervical approach: anatomical study and
      clinical analysis of 69 patients.
AB  - OBJECT: The aim of this study was to describe six variations of the extreme
      lateral craniocervical approach, their application, and treatment results.
      METHODS: During a 4-year period 69 patients underwent surgery in which six
      variations of the extreme-lateral craniocervical approach were performed. The
      variations included: the transfacetal approach (TFA), performed to treat four
      lesions in the upper cervical spine anterior or anterolateral to the spinal cord;
      the retrocondylar approach, to treat five intradural lesions located
      anterolateral to the medulla oblongata and six vascular lesions to expose the
      extradural segment of the vertebral artery (VA); the partial transcondylar
      approach (PTCA), to treat 18 intradural lesions located anterior to the medulla
      oblongata; the complete transcondylar approach (CTCA), to treat 13 extradural
      lesions that involved the lower clivus and anterior upper cervical spine; the
      extreme-lateral transjugular approach, to treat 14 jugular foramen tumors; and
      the transtubercular approach with or without division of the sigmoid sinus, to
      treat complex VA and vertebrobasilar junction aneurysms. An anatomical prosection
      was performed to study the surgical exposure of each of the six variations of the
      extreme-lateral craniocervical approach. Total removal was achieved in 35 (69%)
      of the patients with tumor; subtotal resection was achieved in 16 (31%) of those
      patients. In the 12 patients with VA aneurysms, seven underwent clipping, three
      underwent trapping and a vein graft bypass procedure, and two underwent trapping
      without the use of a bypass procedure. In five other patients, different cystic,
      inflammatory, and other vascular lesions were successfully treated. Fifty percent
      of the patients who underwent surgery via the TFA, 83% via the of the CTCA, and
      11% via the PTCA required an occipitocervical fusion procedure. The mean
      Karnofsky Performance Scale score was 74.7 preoperatively and 76.4
      postoperatively. Major complications were hydrocephalus (nine patients),
      cerebrospinal fluid leakage (seven patients), worsened cranial nerve function
      (seven patients), vertebrobasilar vasospasm (one patient), and sigmoid sinus
      thrombosis (one patient). CONCLUSIONS: To treat lesions in the region of the
      foramen magnum and surrounding areas, the approach should be tailored to each
      specific lesion to provide the needed exposure without unnecessary operative
      steps.

PMID- 10199251
TI  - Vascular endothelial growth/permeability factor in spinal cord injury.
AB  - OBJECT: Predicated on the hypothesis that this cytokine can contribute to the
      development of vascular hyperpermeability, leading to tissue edema after trauma,
      the purpose of this study was to determine the presence in tissue of vascular
      endothelial growth/permeability factor (VEG/PF) after experimental spinal cord
      injury. METHODS: The presence of VEG/PF was studied at 8 hours and 2, 8, and 14
      days after a traumatic injury in adult Wistar rats. Studies were conducted in
      which a monoclonal antibody to the VEG/PF was used. Strong VEG/PF
      immunoreactivity was detected in the walls of pial and intramedullary vessels and
      in reactive astrocytes 8 hours posttrauma and was unchanged on Days 2 and 8. By
      Day 14, immunoreactivity decreased, and most of the arterioles from the pia and
      gray matter showed no mural VEG/PF. CONCLUSIONS: The authors' present findings
      suggest a role for this cytokine in the development of tissue edema after spinal
      cord trauma and point to the possible usefulness of a therapeutic approach to
      spinal cord injury based on blocking the cell expression of VEG/PF or its
      physiological effects.

PMID- 10199252
TI  - Use of porous hydroxyapatite graft containing recombinant human bone
      morphogenetic protein-2 for cervical fusion in a caprine model.
AB  - OBJECT: The efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2)
      for enhancing anterior cervical spine interbody fusion when added to a porous
      hydroxyapatite (HA) graft was investigated. METHODS: Fourteen mature goats
      underwent three-level anterior discectomies after induction of endotracheal
      anesthesia. Porous HA grafts that contained 0, 5, and 50 microg of rhBMP-2 were
      placed concurrently with anterior cervical spine plates to achieve interbody
      fusion. The fusion rate, radiological findings, biomechanical stiffness, and
      histological appearance were evaluated in 42 spinal units immediately and again
      at 4 and 12 weeks after graft and plate placement. At 12 weeks postsurgery,
      manual testing showed a 100% fusion rate in the spines with HA grafts containing
      high-dose rhBMP-2; however, only a 50% fusion rate was shown in spines with
      grafts that contained no or low-dose rhBMP-2. On radiographic and histological
      studies the process of solid fusion was seen to be more advanced in relation to
      the use of larger amounts of rhBMP-2. Biomechanical testing demonstrated
      significantly higher stiffness values for grafts that contained high-dose rhBMP-2
      than those without rhBMP-2 in flexion at 4 weeks, as well as in flexion,
      extension, and lateral bending tests at 12 weeks. Histological analysis
      demonstrated that rhBMP-2 increased the amount of bone apposition on the surface
      of the implants and promoted bone formation in the porous structure without
      increasing the penetration distance. CONCLUSIONS: Through osteogenesis at the
      fusion site, the addition of rhBMP-2 to a porous HA ceramic graft enhances the
      rate of anterior cervical fusion.

PMID- 10199253
TI  - Spinal cord ganglioglioma in a child with neurofibromatosis type 2. Case report
      and literature review.
AB  - Gangliogliomas of the spinal cord are rare disease entities that occur in early
      childhood. Their occurrence in association with neurofibromatosis Type 2 (NF2)
      has not been described. The authors describe the unique case of a 2-year-old
      child with stigmata of NF2 who harbored a spinal cord ganglioglioma that
      presented as a rapidly growing, exophytic intramedullary mass lesion at the
      cervicomedullary junction. Treatment consisted of complete surgical resection.
      Histopathological analysis of the lesion demonstrated a mixed population of
      neoplastic cells, of both neuronal and glial lineage, that supported the
      diagnosis of ganglioglioma.

PMID- 10199254
TI  - De novo development of a cavernous malformation of the spinal cord following
      spinal axis radiation. Case report.
AB  - Analysis of recent reports has suggested that cavernous malformations (CMs) of
      the brain may have an acquired pathogenesis and a dynamic pathophysiological
      composition, with documented appearance of new lesions in familial cases and
      following radiotherapy. The authors report the first case of demonstrated de novo
      formation of an intramedullary CM following spinal radiation therapy. A 17 year
      old boy presented with diabetes insipidus and delayed puberty. Evaluation of
      endocrine levels revealed hypopituitarism, and magnetic resonance (MR) imaging
      demonstrated an infundibular mass. The patient underwent a pterional craniotomy
      and removal of an infundibular germinoma. The MR image of the spine demonstrated
      normal results. The patient received craniospinal radiation therapy and did well.
      He presented 5 years later with acute onset of back pain, lower-extremity
      weakness and numbness, and difficulty with urination. An MR image obtained of the
      spine revealed an intramedullary T-7 lesion; its signal characteristics were
      consistent with a CM. The patient was initially managed conservatively but
      developed progressive myelopathy and partial Brown-Sequard syndrome. Although he
      received high-dose steroids and bed rest, his symptoms worsened. He underwent a
      costotransversectomy and excision of a hemorrhagic vascular lesion via an
      anterolateral myelotomy. Pathological examination confirmed features of a CM. The
      patient has done well and was walking without assistance within 4 weeks of
      surgery. De novo genesis of CMs may be associated with prior radiation therapy to
      the spinal cord.

PMID- 10199255
TI  - Lobular capillary hemangioma of the cauda equina. Case report.
AB  - This 56-year-old woman presented with a 1-year history of low-back pain,
      sciatica, and paresthesias in the right S-1 dermatome. On examination the patient
      was shown to have a right-sided Lasegue's sign, normal strength, hypalgesia in
      the right S-1 dermatome, and a slight diminution of the right Achilles tendon
      reflex. Magnetic resonance imaging revealed a 2-cm intradural enhancing lesion at
      the level of the L-4 vertebra. Laminectomy of L3-L5 vertebrae was performed, and
      intradural exploration disclosed a blueberry-appearing tumor that was surrounded
      by an intense arachnoiditis and attached to the right S-1 nerve root. A cystic
      collection of cerebrospinal fluid was seen caudal to the tumor. Complete removal
      required transection of the adherent nerve root fascicles. Histological analyses
      indicate that the lesion was a lobular capillary hemangioma, which, to the
      authors' knowledge, appears to be one of the first recorded examples of such a
      case.

PMID- 10199256
TI  - Chronic renal failure causing brown tumors and myelopathy. Case report and review
      of pathophysiology and treatment.
AB  - Brown tumors (osteoclastomas) are histologically benign lesions that are caused
      by primary or secondary hyperparathyroidism. Secondary hyperparathyroidism is a
      frequent complication of chronic renal failure. Skeletal brown tumors are
      relatively uncommon, and brown tumors that involve the spine are considered very
      rare. The authors present the case of a 37-year-old woman with systemic lupus
      erythematosus and hemodialysis-dependent anuric renal failure, in whom spinal
      cord compression developed due to a brown tumor and pathological fracture at T-9.
      The patient underwent transthoracic decompressive surgery and spinal
      reconstruction in which cadaveric femoral allograft and instrumentation were
      used. Brown tumors of the vertebral column require surgical treatment if medical
      therapy and parathyroidectomy fail to halt their progression or if acute
      neurological deterioration occurs. In patients with renal failure bone healing is
      delayed and there is an increased risk that healing will fail because the
      metabolic derangements can result in severe osteoporosis. Surgical reconstruction
      of the spine may require the use of augmentation with instrumentation and
      aggressive treatment of hyperparathyroidism to achieve successful outcomes.

PMID- 10199257
TI  - Neurocytoma of the cauda equina. Case report.
AB  - A case of a neurocytoma involving a nerve root of the cauda equina in a 46-year
      old woman is reported. The patient presented with a 2-month history of
      progressive left lower-extremity weakness and pain and decreased ability to walk,
      as well as complaints of incomplete voiding. A magnetic resonance image revealed
      a 7-mm oval mass that was located intrathecally and extended from T-12 to L-1 and
      was adjacent to a nerve root. No lesions were identified at higher vertebral
      levels. The mass was excised. On histological examination it was found to have
      classical features of a neurocytoma. To the best of the authors' knowledge, this
      is the first report of a neurocytoma occurring in that region. A detailed
      histological description of this case and review of the pertinent literature are
      provided.

PMID- 10199258
TI  - Intraspinal epidermoid cyst occurring 15 years after lipomyelomeningocele repair.
      Case report.
AB  - The authors report the case of a spinal epidermoid cyst that developed in a
      patient who had undergone surgery for lipomyelomeningocele repair 15 years
      earlier. The patient presented with symptoms of retethering. Magnetic resonance
      imaging revealed a cystic intraspinal mass that extended from L-2 to L-5. The
      mass proved to be an epidermoid cyst. Spinal epidermoid cysts can cause
      retethering after a repair of lipomyelomeningocele, and the risk of this
      development can be present for decades.

PMID- 10199259
TI  - Subdural hematoma from a Type I spinal arteriovenous malformation. Case report.
AB  - The authors report a patient in whom a subdural hematoma developed from a Type I
      spinal arteriovenous malformation (AVM). The patient became symptomatic with back
      pain, and magnetic resonance imaging revealed a spinal subdural hematoma.
      Selective spinal angiography, however, failed to demonstrate a pathological
      process. The patient underwent exploratory laminoplasty that revealed a subdural
      extraarachnoid hematoma with an underlying Type I spinal AVM, which was
      surgically obliterated. The patient recovered completely. Subdural hematomas that
      affect the spine are rare. Although a negative result was obtained using
      selective spinal angiography, exploratory surgery should be considered for the
      evacuation of a subdural hematoma and possibly for the definitive treatment of a
      spinal AVM.

PMID- 10199260
TI  - Imaging features in combined atlantoaxial and occipitoatlantal rotatory
      subluxation: a rare entity. Case report.
AB  - The authors report a new case of combined atlantoaxial and occipitoatlantal
      rotatory subluxation in a 17-year-old girl. They describe the clinical and
      imaging features of this rare entity. An occiput-C2 arthrodesis was performed.

PMID- 10199261
TI  - Ossification of the cervical anterior longitudinal ligament contributing to
      dysphagia. Case report.
AB  - The authors evaluated the clinical, radiological, and surgical management of
      ossification of the anterior longitudinal ligament (OALL) that contributed to
      dysphagia in a patient with simultaneous cervical ossification of the posterior
      longitudinal ligament (OPLL). A 57-year-old man presented with increasing
      dysphagia and moderate myelopathy. Imaging studies, including esophagoscopy,
      revealed marked esophageal compression due to OALL that extended between the C2-5
      levels and significant C5-7 OPLL that compressed the distal cervical spinal cord.
      The use of rongeurs and a high-speed drill facilitated excision of the C2-5 OALL
      mass, and a routine anterior corpectomy with fusion was performed at the C5-7
      level. Postoperatively, the patient's dysphagia and symptoms of myelopathy
      immediately resolved. The strut graft became fully fused 3 months
      postoperatively, as demonstrated on dynamic x-ray films, and the patient has
      remained asymptomatic 4 months postoperatively. Patients with dysphagia and
      coexisting myelopathy benefit from simultaneous surgery for resection of OALL and
      OPLL masses.

PMID- 10199262
TI  - Posterior epidural migration of sequestered lumbar disc fragments. Report of two
      cases.
AB  - The posterior epidural migration of sequestered lumbar disc fragments is an
      uncommon event. The authors report two such cases in which patients presented
      with either intense radicular pain or cauda equina syndrome. The radiological
      characteristics were the posterior epidural location and the ring enhancement of
      the mass after injection of contrast material. The major diagnostic pitfalls are
      discussed.

PMID- 10199263
TI  - Bilateral sagittal split mandibular osteotomies as an adjunct to the transoral
      approach to the anterior craniovertebral junction. Technical note.
AB  - Transoral approaches are used to expose the craniovertebral junction anteriorly.
      In patients in whom there is limited mandibular excursion, the placement of
      retractors and/or surgical instruments is difficult, and midline "stairstep split
      mandibulotomy" has been advocated as an adjunctive procedure. Although effective,
      this approach requires external splitting of the lip as well as median glossotomy
      or a lateral mucosal incision. The purpose of this study was to show that
      bilateral sagittal split mandibular osteotomies (BSSMOs), which are used in
      orthognathic surgery, represent a safer and more effective alternative to the
      stairstep split mandibulotomy when performed as an adjunct to the transoral
      approach because all incisions are intraoral and the plane of retraction is
      rostrocaudal instead of lateral. Hospital records and radiographic files of four
      patients who underwent BSSMO/transoral approach for odontoidectomy between 1994
      and 1997 were reviewed retrospectively. There were three women and one boy (mean
      age 37.8 years, range 11-68 years). Predisposing conditions included rheumatoid
      arthritis (two patients), Klippel-Feil syndrome (one patient), and congenital
      occipitocervical instability (one patient). Jaw mobility was limited in all
      patients. In addition, one patient had macroglossia, another micrognathia, and
      another retrognathia. The BSSMO provided excellent exposure for resection of the
      odontoid process, as verified on follow-up magnetic resonance imaging or
      computerized tomography studies obtained in all patients. All mandibles were
      rigidly fixed by placing anterior mandibular border titanium plates and
      unicortical screws, and there was no incidence of nonunion or of lingual or
      inferior alveolar nerve injuries. The mean follow-up period was 26 months. The
      BSSMO is an excellent, less invasive adjunct to the transoral approach in
      patients with limited jaw mobility.

PMID- 10199264
TI  - A new occipitocervical fusion construct in pediatric patients with
      occipitocervical instability. Technical note.
AB  - Posterior occipitocervical stabilization procedures were successfully performed
      in 10 patients (nine boys and one girl) 16 years of age or younger by using C1-2
      transarticular screws coupled with a rigid occipitocervical construct. The
      average length of follow-up evaluation was 18.8 months (range 5-37 months). No
      implant failed and all fusions were successful without the use of an external
      orthotic halo device.

PMID- 10199265
TI  - Tuberculosis causing secondary basilar impression. Case illustration.

PMID- 10199266
TI  - Acute hydrocephalus following lateral C1-2 puncture. Case illustration.

PMID- 10199267
TI  - Of geese and golden eggs.

PMID- 10199268
TI  - Formation of phalanges and small joints by tissue-engineering.
AB  - BACKGROUND: This report describes the formation of small phalanges and whole
      joints from three types of bovine-cell sources transplanted onto biodegradable
      polymer matrices. The resulting structures had the shape and composition of human
      phalanges with joints. METHODS: Fresh bovine periosteum was wrapped around a
      copolymer of polyglycolic and poly-L-lactic acid. Separate sheets of polyglycolic
      acid polymer were then seeded with chondrocytes and tenocytes isolated from the
      shoulders of freshly killed calves. The gross form of a composite tissue
      structure was constituted in vitro by assembling the parts and suturing them to
      create models of a distal phalanx, a middle phalanx, and a distal interphalangeal
      joint. RESULTS: Subcutaneous implantation of the sutured composite tissues into
      athymic mice resulted in the formation, after twenty weeks, of new tissue with
      the shape and dimensions of human phalanges with joints. Histological examination
      revealed mature articular cartilage and subchondral bone with a tenocapsule that
      had a structure similar to that of human phalanges and joints. There was
      continuous cell differentiation at the ectopic site even after extended periods.
      CONCLUSIONS: These findings suggest that the formation of phalanges and small
      joints is possible with the selective placement of periosteum, chondrocytes, and
      tenocytes into a biodegradable synthetic polymer scaffold.

PMID- 10199269
TI  - Delay in the diagnosis and treatment of primary bone sarcoma of the pelvis.
AB  - BACKGROUND: Symptoms arising from primary bone sarcoma of the pelvic girdle are
      often insidious in onset and nonspecific in nature. To make the subtle initial
      signs and symptoms of these tumors more apparent to clinicians, we studied a
      cohort of patients who had a primary bone sarcoma of the pelvic girdle. Our
      purpose was to describe the initial clinical findings and to evaluate the
      duration, frequency, and implications of delays in the treatment of these tumors.
      METHODS: We retrospectively analyzed the data on sixty-eight patients who had a
      primary bone sarcoma of the pelvic girdle. The data that we reviewed included
      demographic characteristics; histological diagnosis; anatomical location, size,
      and stage of the tumor; characteristics of the biopsy specimen; duration and
      description of symptoms before an accurate diagnosis was made; delay before
      recognition of the tumor on radiographs; results of diagnostic imaging;
      inaccurate diagnoses; type of intervention based on these inaccurate diagnoses;
      and outcome with regard to survival. There were forty high-grade sarcomas and
      twenty-eight low-grade sarcomas. RESULTS: Excluding two asymptomatic patients in
      whom the sarcoma was noted incidentally, the average duration of symptoms before
      an accurate diagnosis was made was ten months (median, six months; range, one
      month to four years). Common symptoms and findings on physical examination
      included pain in the buttock (twenty-three patients; 35 percent), a mass (twenty
      patients; 30 percent), sciatica (nineteen patients; 29 percent), pain in the hip
      (seventeen patients; 26 percent), pain in the groin (thirteen patients; 20
      percent), and low-back pain (fourteen patients; 21 percent). In thirty (44
      percent) of the sixty-eight patients, the pelvic sarcoma was not recognized
      initially and an inaccurate diagnosis was made. The misdiagnoses included a
      herniated lumbar disc, spinal stenosis, spondylolisthesis, tendinitis, bursitis,
      an inguinal hernia, a stress fracture, a pilonidal cyst, a recurrent urinary
      tract infection, and degenerative arthritis of the spine, hip, and knee.
      Inappropriate treatment for these misdiagnoses included seven operative
      procedures (two laminectomies, two debridements, one hip arthrotomy, one total
      knee replacement, and one inguinal herniorrhaphy), six courses of nonsteroidal
      anti-inflammatory medications, five chiropractic adjustments, four trials of
      physical therapy, and three local injections of steroids. It took an average of
      seven months for the clinicians to arrive at the diagnosis of primary pelvic
      sarcoma. With the numbers available, no significant association between the
      duration of symptoms before an accurate diagnosis was made and the grade or the
      stage of the tumor could be detected. In addition, no association between the
      duration of symptoms and the survival of the patient (p = 0.54) could be
      determined, with univariate analysis. The grade and the stage of the tumor were
      strongly associated with the outcome, with a low tumor grade proving to be a
      favorable prognostic indicator for survival (p = 0.006). CONCLUSIONS: Patients
      who have a primary bone sarcoma of the pelvis often have had symptoms for a long
      duration that mimic those of more commonly encountered non-neoplastic
      musculoskeletal conditions. When a patient has symptoms that appear to be out of
      the ordinary, particularly refractory pain or pain at rest, physicians should
      include the pelvic girdle in the evaluation and should carefully examine a high
      quality radiograph of the entire pelvis.

PMID- 10199270
TI  - Chondrosarcoma of bone: an assessment of outcome.
AB  - BACKGROUND: The data on 227 patients who had been managed for a chondrosarcoma at
      one institution were reviewed to determine the nature of the lesions, the
      predictors of outcome, and whether there were any ways to change the treatment
      approaches to improve the results. METHODS: The patients were followed for a mean
      duration of six years (range, three to twenty-five years). The mean age of the
      patients was forty-seven years (range, nine to eighty-four years). The most
      prevalent sites of the tumors were the femur (seventy-eight), the pelvis (fifty
      one), and the humerus (thirty-nine). The tumors were divided into two groups
      according to histological grade. Eighty-six tumors (sixteen atypical enchondromas
      and seventy grade-1 chondrosarcomas) that were locally destructive but were
      associated with a low likelihood of metastasis were considered to be low-grade.
      The remaining 141 lesions, which were locally destructive, potentially
      metastatic, and capable of causing death, were thought to be high-grade. One
      hundred and three of these 141 lesions were grade 2, and thirty-eight were grade
      3 (eighteen of the thirty-eight were grade 3 only, and twenty were both grade 3
      and dedifferentiated). Two hundred and twenty-four patients were managed with
      resection and a limb-sparing procedure; the remaining three patients had an
      amputation. Postoperative adjuvant radiation was used for fifty-six patients;
      chemotherapy, for thirty-five; and both radiation and chemotherapy, for nineteen.
      Flow cytometric patterns were analyzed for 105 patients. RESULTS: The patients
      who had a high-grade tumor were older than those who had a low-grade tumor (mean
      age [and standard deviation], 50+/-17.0 years compared with 40+/-15.9 years; p <
      0.001). Pathological fracture, metastasis, local recurrence, and death were more
      prevalent in the group that had a high-grade lesion (p < 0.001). Predictors of
      metastasis and death in that group of patients included local recurrence, a
      pelvic location of the tumor, a tumor that was more than 100 cubic centimeters in
      size, a ploidic abnormality (aneuploidy coupled with a high mean DNA index), a
      histological grade of 3, and a dedifferentiated type of tumor (p < 0.001).
      CONCLUSIONS: Although the data are suggestive, with the numbers available for
      study we could not detect a significant difference in the rates of pulmonary
      metastasis and death between the patients who had a grade-3 lesion and those who
      had a grade-3 lesion that was also dedifferentiated. However, the interval
      between diagnosis and death was 32+/-22.8 months for the patients who had a grade
      3 lesion compared with 5+/-3.7 months for those who had a grade-3 lesion that was
      also dedifferentiated (p < 0.001). Overall, patients who had had a resection with
      wide margins (margins extending outside the reactive zone) had a longer duration
      of survival than did those who had had a so-called marginal resection (margins
      extending outside the tumor but within the reactive zone) or an intralesional
      resection (margins within the lesion) (p < 0.04). Adjunctive chemotherapy or
      radiation, or both (which, it must be noted, was used, without a protocol, in a
      relatively small number of patients), after an intralesional resection, for
      recurrent disease, or for distant metastasis did not appear to alter the outcome.

PMID- 10199271
TI  - Thromboembolic prophylaxis with use of aspirin, exercise, and graded elastic
      stockings or intermittent compression devices in patients managed with total hip
      arthroplasty.
AB  - BACKGROUND: Prophylaxis against pulmonary embolism as a complication of total hip
      arthroplasty remains controversial. Our experience suggests that an inexpensive
      protocol of prophylaxis that includes aspirin and exercise is effective. METHODS:
      We investigated the effectiveness of aspirin, a program of intraoperative and
      postoperative exercises, and graded elastic stockings or intermittent compression
      devices as prophylaxis against thromboembolic disease in a series of 1267
      patients who had had 1492 total hip arthroplasties. All of the operations were
      done through a posterior approach. For the purpose of this review, the duration
      of follow-up was limited to a minimum of three months. No patient was lost to
      follow-up. Any thromboembolic complications that may have occurred after the
      third postoperative month were not considered to be related to the operation and
      were not recorded. RESULTS: A fatal pulmonary embolism occurred after two
      arthroplasties (0.13 percent), a nonfatal pulmonary embolism was diagnosed after
      fourteen (0.94 percent), and deep venous thrombosis developed after fifteen (1.01
      percent). Regional (epidural) anesthesia was used for 1099 arthroplasties (73.7
      percent), and general anesthesia was used for 393 procedures (26.3 percent). A
      fatal pulmonary embolism occurred after two (0.18 percent) of the 1099
      arthroplasties that had been performed with regional anesthesia and after none
      that had been performed with general anesthesia (chi square = 0.22; p > 0.05). A
      nonfatal pulmonary embolism occurred after two procedures (0.18 percent) that had
      been done with regional anesthesia and after twelve (3.05 percent) that had been
      done with general anesthesia (chi square = 25.3; p < 0.001). Deep venous
      thrombosis was diagnosed after seven procedures (0.64 percent) that had been
      performed with regional anesthesia and after eight (2.04 percent) that had been
      performed with general anesthesia (chi square = 5.45; p < 0.025). We detected a
      significant difference between men and women with respect to the rate of nonfatal
      pulmonary embolism (chi square = 4.36; p < 0.05). With the numbers available, we
      found no significant differences between the 774 arthroplasties (51.9 percent) in
      patients who had worn graded elastic stockings and the 718 arthroplasties (48.1
      percent) in patients who had used intermittent compression devices, between the
      774 arthroplasties (51.9 percent) that had been performed in Florida and the 718
      (48.1 percent) that had been done in California, or between the 1313 primary
      arthroplasties (88 percent) and the 179 revision arthroplasties (12 percent),
      with regard to the prevalence of fatal pulmonary embolism, nonfatal pulmonary
      embolism, or deep venous thrombosis (p > 0.05 for all comparisons). In summary,
      we found that the type of compression (graded elastic stockings or intermittent
      compression devices), the geographic location (California or Florida), and the
      type of operation (primary or revision) had no significant effect, with the
      numbers available, on the rate of thromboembolic complications. Compared with
      general anesthesia, the use of regional anesthesia was associated with a
      significantly lower rate of nonfatal pulmonary embolism (p < 0.001) and deep
      venous thrombosis (p < 0.025). Both patients who had a fatal pulmonary embolism
      had had regional anesthesia (p > 0.05). CONCLUSIONS: This inexpensive method of
      prophylaxis against thromboembolic disease after total hip arthroplasty, which
      was based primarily on the use of aspirin as the pharmacological agent and the
      performance of intraoperative and postoperative exercises, produced good clinical
      results.

PMID- 10199272
TI  - Total hip arthroplasty with insertion of the acetabular component without cement
      in hips with total congenital dislocation or marked congenital dysplasia.
AB  - BACKGROUND: End-stage osteoarthritis secondary to total congenital dislocation or
      severe congenital dysplasia of the hip (class B or C according to the system of
      Eftekhar or type 2 or 3 according to the system of Hartofilakidis et al.) in
      adults presents special problems with regard to reconstruction of the hip. The
      purpose of the present study was to assess the intermediate-term results
      associated with the use of a porous ingrowth acetabular component for the
      treatment of these difficult cases. METHODS: We performed a prospective study of
      a consecutive series of twenty-one patients (twenty-four hips) who had had a
      primary total hip arthroplasty with use of a hemispherical acetabular component
      that was inserted without cement and fixed with screws. No patient was lost to
      follow-up. Three patients (four hips) died, of causes unrelated to the total hip
      arthroplasty, before a minimum duration of follow-up of five years. None of these
      patients had had revision. Of the remaining eighteen patients (twenty hips),
      fifteen were women and three were men. Ten hips had total dislocation, and ten
      had severe dysplasia. RESULTS: After an average duration of follow-up of eighty
      three months (range, sixty-four to 102 months), the average Harris hip score was
      90 points (range, 68 to 97 points). No patient had revision, loosening, or
      migration of the acetabular component; pelvic osteolysis; or a continuous
      radiolucent line at the mesh-bone interface of the acetabular component. The
      average rate of polyethylene wear was 0.08 millimeter per year (range, zero to
      0.21 millimeter per year). CONCLUSIONS: The porous ingrowth acetabular component
      that was used in the present study functioned well at the time of the
      intermediate-term follow-up of this group of patients who had marked congenital
      dysplasia or total dislocation of the hip. The use of this component decreased
      the need for structural acetabular grafts. This component appears to perform as
      well as larger components of this design that have been assessed after similar
      durations of follow-up.

PMID- 10199273
TI  - An outcome study of chronic patellofemoral pain syndrome. Seven-year follow-up of
      patients in a randomized, controlled trial.
AB  - BACKGROUND: We determined prospectively the long-term outcomes of nonoperative
      treatment of chronic patellofemoral pain syndrome. METHODS: Of forty-nine
      patients in a prospective, randomized, double-blind study of unilateral chronic
      patellofemoral pain syndrome in the knee, forty-five were reexamined seven years
      after the initial trial of treatment. In the earlier trial, the short-term (six
      month) effects of intra-articular injections of glycosaminoglycan polysulfate
      combined with intensive quadriceps-muscle exercises were compared with those of
      injections of a placebo combined with exercises and with those of exercises
      alone. At seven years, the follow-up consisted of standardized subjective,
      functional, and clinical assessments and muscle-strength measurements as well as
      magnetic resonance imaging, radiography, and bone-densitometry measurements of
      the knee. RESULTS: At six months, complete subjective, functional, and clinical
      recovery had occurred in almost three-fourths of the patients and, with the
      numbers available for study, neither significant nor clinically important
      differences among the three initial treatment groups were detected. The
      subjective and functional parameters showed few changes between six months and
      seven years; almost three-fourths of the patients still had full subjective and
      functional recovery at the time of the latest follow-up. However, according to
      the physician's clinical evaluation, the number of patients who had no symptoms
      on the patellar compression and apprehension tests decreased over time, from
      forty-two (93 percent) and forty (89 percent) of forty-five patients at six
      months to thirty (67 percent) and thirty-one (69 percent) at seven years; these
      changes were significant (p = 0.002 and p = 0.023, respectively). The number of
      patients who had crepitation on the patellar compression test increased over
      time, from twenty-six (58 percent) at six months to thirty-six (80 percent) at
      seven years (p = 0.021). The physician's overall assessment showed a similar
      trend, with thirty-four patients (76 percent) having had complete recovery at six
      months compared with thirty (67 percent) at seven years; however, with the
      numbers available, this change was not significant (p = 0.420). Magnetic
      resonance imaging, performed for thirty-seven patients, revealed no abnormalities
      in twenty-four (65 percent), mild abnormalities in four (11 percent), moderate
      abnormalities (a 25 to 75 percent decrease in the thickness of the cartilage) in
      seven (19 percent), and overt patellofemoral osteoarthritis in two (5 percent) at
      seven years. CONCLUSIONS: The seven-year overall outcome was good in
      approximately two-thirds of the patients. However, the remaining patients still
      had symptoms or objective signs of a patellofemoral abnormality.

PMID- 10199274
TI  - Radiographic evaluation of the position of implants in the medial malleolus in
      relation to the ankle joint space: anteroposterior compared with mortise
      radiographs.
AB  - BACKGROUND: Displaced transverse fractures of the medial malleolus are commonly
      treated with open reduction and internal fixation with two screws or wires. A
      mortise radiograph is often used to verify the position of the implants relative
      to the joint space. However, because the medial and lateral talomalleolar spaces
      are normally not parallel, the mortise projection (which is colinear with the
      lateral space) does not provide an accurate radiograph of the medial joint space.
      METHODS: In ten cadaveric ankles, two wires were inserted into the medial
      malleolus, as is done for fixation of a fracture, and the distance of the wires
      from the joint space was measured on an anteroposterior radiograph, on mortise
      radiographs made with the foot in 15 and 30 degrees of internal rotation, and on
      anatomical cross section. RESULTS: The measurement on the anteroposterior
      radiograph exceeded the anatomical measurement in only two specimens, and the
      discrepancy was 0.5 millimeter in both instances. Measurement of the osseous
      thickness between the joint surface and the posterior wire on the mortise
      radiographs always revealed a lower value than the measurements on the
      anteroposterior radiograph and the anatomical cross section of the same specimen.
      There was a false appearance of intra-articular placement of the posterior wire
      on the 15-degree mortise radiographs of four specimens and on the 30-degree
      mortise radiographs of eight specimens. CONCLUSIONS: These findings demonstrate
      that the mortise projection provides an oblique radiograph of the medial joint
      space that can inaccurately reflect the true position of fixation implants in the
      medial malleolus. Because an anteroposterior radiograph is made with the
      articular surface of the medial malleolus tangential to the beam, it provides a
      more accurate representation of implants in the medial malleolus.

PMID- 10199275
TI  - Relationship between clinical measurements and motion of the first
      metatarsophalangeal joint during gait.
AB  - BACKGROUND: The range of joint motion is a commonly reported outcome measure in
      assessment of the great toe. Although motion of the first metatarsophalangeal
      joint during gait is of primary functional importance, clinicians rely on
      relatively static clinical measures to assess this joint. The relationship
      between the results of commonly used clinical tests of motion of the first
      metatarsophalangeal joint and motion of this joint during gait was assessed in a
      study of thirty-three subjects who had no history of a pathological condition of
      the foot or ankle. METHODS: An electromagnetic tracking device was used to
      acquire three-dimensional orientation data on the hallux with respect to the
      first metatarsal. Receivers were secured to the skin overlying the proximal
      phalanx of the hallux, the first metatarsal, and the medial aspect of the
      calcaneus. Measurements were recorded during four clinical tests. These tests
      assessed the active range of motion of the first metatarsophalangeal joint with
      the subject weight-bearing, the passive range of motion with the subject weight
      bearing, the passive range of motion with the subject non-weight-bearing, and the
      motion during a heel-rise. The data collected with these tests were compared with
      motion of the first metatarsophalangeal joint during walking. The focus of the
      analysis was the dorsiflexion component of rotation. RESULTS: With the exception
      of the passive range of motion with the subject weight-bearing, the ranges of
      motion measured during all of the clinical tests exceeded the motion of the first
      metatarsal joint that is required during normal walking. The motion measured
      during heel-rise (r = 0.87, p < 0.001) and the active range of motion with the
      subject weight-bearing (r = 0.80, p < 0.001) had the strongest correlations with
      motion of the first metatarsophalangeal joint during gait. The mean dorsiflexion
      during the test of the active range of motion (44 degrees) was closer to the mean
      dorsiflexion during gait (42 degrees) than was the mean value measured during the
      heel-rise test (58 degrees). This study also demonstrated that the clinical tests
      are not interchangeable as their mean results differed by as much as 21 degrees.
      CONCLUSIONS: The selection of a reliable and valid clinical test and an
      understanding of the relationship of the results of this test to the motion
      requirements during normal gait will help to standardize reporting techniques and
      will improve the ability of the clinician to determine the outcomes of treatment.
      This study showed that measurement of the active range of motion with the subject
      weight-bearing was a reliable and valid test and that the results were strongly
      correlated with motion of the first metatarsophalangeal joint during gait.

PMID- 10199277
TI  - Position of immobilization after dislocation of the shoulder. A cadaveric study.
AB  - BACKGROUND: After reduction of a shoulder dislocation, the torn edges of a
      Bankart lesion need to be approximated for healing during immobilization. The
      position of immobilization has traditionally been adduction and internal
      rotation, but there is little direct evidence to support or discredit the use of
      this position. The purpose of the present study was to determine the relationship
      between the position of the arm and the coaptation of the edges of a simulated
      Bankart lesion created in cadaveric shoulders. METHODS: Ten thawed fresh-frozen
      cadaveric shoulders were used for experimentation. All of the muscles were
      removed to expose the joint capsule. A simulated Bankart lesion was created by
      sectioning the anteroinferior aspect of the capsule from the labrum. With linear
      transducers attached to the anteroinferior and inferior portions of the Bankart
      lesion, the opening and closing of the lesion were recorded with the arm in 0,
      30, 45, and 60 degrees of elevation in the coronal and sagittal planes as well as
      with the arm in rotation from full internal to full external rotation in 10
      degree increments. RESULTS: With the arm in adduction, the edges of the simulated
      Bankart lesion were coapted in the range from full internal rotation to 30
      degrees of external rotation. With the arm in 30 degrees of flexion or abduction,
      the edges of the lesion were coapted in neutral and internal rotation but were
      separated in external rotation. At 45 and 60 degrees of flexion or abduction, the
      edges were separated regardless of rotation. CONCLUSIONS: The present study
      demonstrated that, in the cadaveric shoulder, there was a so-called coaptation
      zone in which the edges of a simulated Bankart lesion were kept approximated
      without the surrounding muscles.

PMID- 10199276
TI  - Results of transfer of the pectoralis major tendon to treat paralysis of the
      serratus anterior muscle.
AB  - BACKGROUND: Paralysis of the serratus anterior muscle can be functionally
      disabling. As a result of the scapular winging associated with such paralysis,
      the scapula does not remain apposed to the thorax when the upper extremity is
      elevated forward at the shoulder. This produces functional disability associated
      with pain and loss of a stable base for movement of the upper extremity. METHODS:
      We reviewed the results of transfer of the pectoralis major tendon with the
      addition of a fascial graft in sixteen patients who had paralysis of the serratus
      anterior. The average age of the patients at the time of the operation was thirty
      three years (range, twenty to fifty-five years). Electrodiagnostic studies
      confirmed the presence of an isolated injury of the long thoracic nerve. The
      index operation was performed sixteen months to eleven years after the onset of
      pain and weakness. The etiology of the paralysis was idiopathic in two patients,
      traumatic in seven, and secondary to operative intervention in seven. All
      patients had pain in the shoulder on the side of the paralysis. RESULTS: The
      result was excellent for eight patients, good for five, and fair for one at an
      average of four years and three months (range, two years and one month to nine
      years) postoperatively. There were two failures, both of which occurred after a
      traumatic event. Of the fourteen patients in whom the procedure did not fail,
      eight were asymptomatic and had normal function, five had intermittent mild
      discomfort, and one had frequent mild pain without any winging of the scapula.
      The average Constant and Murley score for the fourteen patients in whom the
      procedure did not fail increased from 36 points preoperatively to 92 points
      postoperatively. CONCLUSIONS: The index procedure successfully alleviated the
      functional disability caused by paralysis of the serratus anterior muscle.

PMID- 10199278
TI  - Biomechanical evaluation of fixation of intra-articular fractures of the distal
      part of the radius in cadavera: Kirschner wires compared with calcium-phosphate
      bone cement.
AB  - BACKGROUND: The purpose of this study was to compare the biomechanical efficacy
      of an injectable calcium-phosphate bone cement (Skeletal Repair System [SRS])
      with that of Kirschner wires for the fixation of intraarticular fractures of the
      distal part of the radius. METHODS: Colles fractures (AO pattern, C2.1) were
      produced in ten pairs of fresh-frozen human cadaveric radii. One radius from each
      pair was randomly chosen for stabilization with SRS bone cement. These ten radii
      were treated with open incision, impaction of loose cancellous bone with use of a
      Freer elevator, and placement of the SRS bone cement by injection. In the ten
      control specimens, the fracture was stabilized with use of two horizontal and two
      oblique Kirschner wires. The specimens were cyclically loaded to a peak load of
      200 newtons for 2000 cycles to evaluate the amount of settling, or radial
      shortening, under conditions simulating postoperative loading with the limb in a
      cast. Each specimen then was loaded to failure to determine its ultimate
      strength. RESULTS: The amount of radial shortening was highly variable among the
      specimens, but it was consistently higher in the Kirschner-wire constructs than
      in the bone fixed with SRS bone cement within each pair of radii. The range of
      shortening for all twenty specimens was 0.18 to 4.51 millimeters. The average
      amount of shortening in the SRS constructs was 50 percent of that in the
      Kirschner-wire constructs (0.51+/-0.34 compared with 1.01+/-1.23 millimeters; p =
      0.015). With the numbers available, no significant difference in ultimate
      strength was detected between the two fixation groups. CONCLUSIONS: This study
      showed that fixation of an intra-articular fracture of the distal part of a
      cadaveric radius with biocompatible calcium-phosphate bone cement produced
      results that were biomechanically comparable with those produced by fixation with
      Kirschner wires. However, the constructs that were fixed with calcium-phosphate
      bone cement demonstrated less shortening under simulated cyclic load-bearing.

PMID- 10199279
TI  - Metallosis due to impingement between the socket and the femoral neck in a metal
      on-metal bearing total hip prosthesis. A case report.

PMID- 10199280
TI  - Symptomatic osteochondroma of the clavicle. A report of two cases.

PMID- 10199281
TI  - Multifocal, metachronous giant-cell tumor of the ulna. A case report.

PMID- 10199282
TI  - Retirement from orthopaedic surgery.

PMID- 10199284
TI  - Percutaneous radiofrequency coagulation of osteoid osteoma compared with
      operative treatment.

PMID- 10199283
TI  - Charnley total hip arthroplasty in patients less than fifty years old. A twenty
      to twenty-five-year follow-up note.

PMID- 10199285
TI  - Correlation between the measures of impairment, according to the modified system
      of the American Medical Association, and function.

PMID- 10199286
TI  - Treatment of unruptured cerebral aneurysms.

PMID- 10199287
TI  - The projection of the cervical disc and uncinate process on the posterior aspect
      of the cervical spine.
AB  - BACKGROUND: Surgical techniques of foraminotomy for decompression of the cervical
      nerve have been well described in the literature. Excessive resection of the
      facet joint and laminae may decrease segmental stability and increase scar
      formation. How much bony resection is adequate to remove a soft or hard disc
      herniation is not known. No studies regarding this subject are available.
      METHODS: Thirty-nine adult dry bone spines from C3 to C7 were used and four
      measurements on each vertebra were taken in this study. The first three
      measurements included the vertical distances between the superior borders of the
      lamina and the vertebral body measured at the midline of the laminae, the middle
      of the lamina, and the lamina-facet junction, respectively. The fourth was the
      horizontal distance between the medial most border of the superior facet and the
      tip of the uncinate process. RESULTS: No significant differences between male and
      female specimens were found in any measurements in this study. The mean vertical
      distances from the superior border of the lamina inferior to the superior border
      of the vertebral body measured at the three points for all levels were
      approximately 1-3 mm, although the standard deviations for those were relatively
      high. The tip of the uncinate process was located from 2 mm at C3 to 1 mm at C6
      medial to the medial most border of the superior facet, and then changed to be
      located 1 mm lateral to the medial most border of the superior facet.
      CONCLUSIONS: This study suggests that a semicircular laminotomy placed on the
      inferior aspect of the lamina above may be adequate for a lateral soft disc
      herniation because the inferior border of the disc is higher than the superior
      border of the inferior lamina, whereas a traditional foraminotomy is needed for a
      hard disc pathology.

PMID- 10199288
TI  - Surgical approach to ossification of the thoracic yellow ligament.
AB  - BACKGROUND: Symptomatic ossification of the yellow ligament (OYL) at the lower
      thoracic level is uncommon. Although wide laminectomy has, until now, been the
      primary treatment for this disease, we propose a less invasive technique based on
      a new method of three-dimensional computed tomography (CT). METHODS: The clinical
      features and radiologic imaging findings of 37 patients with OYL (mean age, 54
      years) were analyzed. The surgical approach was selected based on the position of
      the depicted OYL on 3D CT scan in each patient. RESULTS: The male-to-female ratio
      was 3:1. Involvement of the upper thoracic region was seen 11 times; of the
      middle region 8 times, and of the lower region 40 times (several patients had
      involvement in more than one region). About half of the patients complained of
      gait disturbance on admission caused by the markedly enlarged OYL. No
      postoperative complications were found. Neurologic deterioration was observed in
      only one patient. CONCLUSIONS: OYL should be treated as early as possible, using
      the least invasive technique available. By using 3D CT, we were able to perform
      limited surgery consisting of foraminotomy or extended partial laminectomy at the
      affected level after confirming the anatomic location of the OYL. In laterally
      extended OYL, it is necessary to decompress the radicular artery in order to
      prevent ischemic damage to the spinal cord.

PMID- 10199289
TI  - Spinal subarachnoid hemorrhage attributable to schwannoma of the cauda equina.
AB  - BACKGROUND: Cauda equina syndrome occurring as a result of spontaneous spinal
      subarachnoid hemorrhage (SAH) from a spinal tumor is reported to be rare. CASE
      DESCRIPTION: A 28-year-old woman presented at our clinic with a history of severe
      back pain for 10 days, progressive paraparesis, and urinary retention. Her
      physical examination revealed a mass located intradurally at the level of L1-2
      and a massive SAH. An L1-L2, laminectomy and a hemilaminectomy from D9 to D12
      were performed and the SAH was evacuated and the cord was decompressed.
      CONCLUSION: At the first year follow-up, her restricted dorsal and plantar
      flexion continued. Post-gadolinium magnetic resonance imaging revealed no mass.

PMID- 10199290
TI  - Arachnoid cysts of the posterior fossa.
AB  - BACKGROUND: The surgical indications and management of posterior fossa arachnoid
      cysts (AC) are still controversial. Different surgical techniques and management
      have already been suggested for arachnoid cysts of the posterior fossa. AC
      involving the posterior fossa and especially the cerebellopontine angle may carry
      a high surgical morbidity because of the involvement of important neurovascular
      structures (e.g., brain stem and cranial nerves). Only long-term follow-up will
      determine the best surgical technique for such lesions. METHODS: Between 1990 and
      1996 a total of 12 patients underwent surgery for arachnoid cysts involving the
      posterior fossa. In seven cases AC were located within the cerebellopontine angle
      (CPA), in three cases in the CPA with major extension dorsal to the brainstem,
      and in two cases at the CPA extending into the internal auditory canal. RESULTS:
      A suboccipital retrosigmoid approach was performed in all patients. Radical
      resection of the cyst could be accomplished in all but one case. There was no
      mortality. Major postoperative morbidity was present in one case because of an
      intraoperative air embolism in the semisitting position and strong adherence of
      the cyst wall to the surrounding neurovascular structures. Long-term follow-up
      (mean, 3.3 years) revealed improvement of most preoperative symptoms. CONCLUSION:
      Open surgery and radical removal of the AC located at the posterior fossa, based
      on our retrospective analysis, provide very good long-term postoperative results.
      The suboccipital approach provides a good and safe exposure of vascular
      structures and cranial nerves in the CPA and allows radical resection of the
      cyst, reducing the chance of recurrence.

PMID- 10199291
TI  - Pediatric syringomyelia with chiari malformation: its clinical characteristics
      and surgical outcomes.
AB  - BACKGROUND: Most reports regarding pediatric syringomyelia have focused not only
      on Chiari malformation, but also on spinal dysraphism. However, the clinical
      characteristics of syringomyelia with spinal dysraphism are quite different from
      those of syringomyelia due to Chiari Type I malformation. The objectives of this
      study were to identify clinical characteristics of pediatric syringomyelia and to
      determine whether surgery prevents or corrects the scoliosis associated with
      syringomyelia. METHODS: We reviewed the records of 16 pediatric patients with
      syringomyelia and Chiari Type I malformation. The patients' ages ranged from 3 to
      15 years, with mean age of 9.8 years. None of the patients had spinal dysraphism.
      RESULTS: Nystagmus was observed in 2 of the 16 patients, motor weakness in 8
      patients, sensory disturbance in 10 patients, and scoliosis in 13 patients. As
      the initial surgical procedure, foramen magnum decompression (FMD) was performed
      in seven patients and syringo-subarachnoid (S-S) shunting in nine patients. The
      motor function improved in 7 of the 8 affected patients, and the sensory
      disturbance improved in 9 of the 10 affected patients. The magnetic resonance
      images obtained after the surgery revealed marked decrease of the syrinx size in
      all patients. Of the 13 patients with scoliosis, 5 showed improvement, 5
      stabilization, and 3 deterioration. CONCLUSIONS: Compared with adolescent and
      adult syringomyelia, pediatric syringomyelia shows a much lower incidence of
      sensory disturbance and pain, but quite a high incidence of scoliosis. Surgery is
      effective in improving or stabilizing scoliosis in these patients.

PMID- 10199292
TI  - A prospective study on the effects of early surgery on vasospasm after
      subarachnoid hemorrhage.
AB  - BACKGROUND: To test the hypothesis that early surgery prevents vasospasm, a
      prospective analysis used strictly selected cases of anterior communicating
      artery aneurysms with symmetric distribution of subarachnoid hemorrhage. METHODS:
      Seven patients underwent early surgery (9-29 hours after ictus) through a
      standard pterional approach. Subarachnoid blood clots surrounding the ipsilateral
      major cerebral arteries were meticulously irrigated and suctioned. Comparison was
      made between the hemispheres with surgical intervention and those without, in
      terms of incidence of delayed ischemic neurologic deficits and cerebral
      infarction on computed tomographic scans, degree of angiographic vasospasm, and
      cerebral blood flow (CBF). RESULT: The degree of angiographic vasospasm,
      quantified by measuring the alterations in the ratio of the diameters of the
      intracranial arteries (C1, M1) to the extracranial internal carotid artery (C5),
      did not differ significantly between the surgical and nonsurgical sides. The mean
      CBF was also comparable between both sides in the chronic spasm phase (Day 6-9)
      as well as in the early postoperative period (Day 1-3). A significant reduction
      of CBF was observed during the early postoperative period in the basal frontal
      lobe of the surgical side. This CBF reduction seems to correspond to brain
      retraction. CONCLUSIONS: The results suggest that the effect of clot removal may
      be offset by the negative aspect of early surgery, and early surgery per se seems
      to have little effect on the course of the chronic vasospasm.

PMID- 10199293
TI  - Morphological changes after percutaneous transluminal angioplasty.
AB  - BACKGROUND: Percutaneous transluminal angioplasty (PTA) dilates constricted
      arteries at the circle of Willis to reverse cerebral ischemia caused by cerebral
      vasospasm. Although 90% of the patients show angiographic improvement after PTA,
      only 70% show clinical improvement. Why some patients do not improve after PTA is
      unknown. We report on a 48-year-old woman who failed to improve after PTA and
      died from aneurysm rerupture. Pathologic studies were performed to determine why
      PTA failed to reverse the symptoms of cerebral ischemia. METHODS: The arteries of
      the brain were studied by light microscopy using Gomori's trichrome stain. The
      arteries were also studied by scanning and transmission electron microscopy.
      RESULTS: The arteries that were dilated with PTA showed compression of the
      connective tissue, stretching of the internal elastic lamina, and a combination
      of compression and stretching of the smooth muscle. The small arteries and
      arterioles that had been treated with an infusion of intraarterial papaverine
      were constricted with a thickened intimal layer. CONCLUSION: The persistence of
      cerebral vasospasm in small and perforating arteries may contribute to the
      failure of cerebral ischemia to reverse after PTA.

PMID- 10199294
TI  - Non-anastomotic bypass surgery for childhood moyamoya disease using dural pedicle
      insertion over the brain surface combined with encephalogaleomyosynangiosis.
AB  - BACKGROUND: Anastomotic bypass surgery for childhood moyamoya disease provides
      more rapid improvement of blood circulation than indirect non-anastomotic bypass
      surgery, but there are several problems, such as the technical difficulty of the
      operation, the extended period of anesthesia, and temporary occlusion of blood
      flow in the vessels of the brain surface. METHODS: We describe a new non
      anastomotic bypass procedure using dural pedicle insertion over the brain surface
      combined with encephalogaleomyosynangiosis and preservation of the superficial
      temporal artery (STA). We treated nine patients with childhood moyamoya disease
      admitted to our institution from 1989 through 1994. The operative field was
      determined based on the ischemic site identified by preoperative neuroimaging
      methods. Our procedure was performed in a total of 15 hemispheres, and the
      patients have been followed up for 5 months to 5 years after operation. RESULTS:
      Cerebral angiography, cerebral blood flow measurements, and clinical symptoms and
      signs were improved at the operation site in all patients. Because the STA and
      the superficial portion of the temporal muscle attached to the skin flap were
      preserved, the skin at the operation site was not depressed and no necrosis,
      infection, or alopecia developed. CONCLUSION: Childhood moyamoya disease is
      progressive, so repeated bypass surgery may be required. Therefore, non
      anastomotic bypass surgery is better for the first operation because the STA is
      preserved. The present procedure using temporal muscle, galea, and dura can be
      extended over a wider brain surface than the operative field, and is suitable for
      establishing collateral circulation in the frontal lobe. Blood flow in the skin
      flap is maintained, so the cosmetic result is satisfactory.

PMID- 10199296
TI  - Operative approach to mediosuperior cerebellar tumors: occipital interhemispheric
      transtentorial approach.
AB  - BACKGROUND: The transtentorial approach is well known as an approach to the
      pineal region. We have modified this approach for mediosuperior cerebellar
      tumors. METHODS: We describe six cases of tumor excision in this region using an
      occipital interhemispheric transtentorial approach. RESULTS: The lesions were
      easily accessible and the tumor was totally removed by this modified approach in
      all cases. Transient visual field disturbance with spontaneous recovery occurred
      in two patients. The lateral margin of the tumor was accessed easily up to 35 mm
      from the midline on the operative side and up to 17 mm from the midline on the
      contralateral side. CONCLUSION: This approach proved to be very useful for
      mediosuperior lesions of the cerebellum, without causing any neural structural
      damage, and allowed for a wider operative field.

PMID- 10199295
TI  - Petroclival meningioma. An attempt to define the role of skull base approaches in
      their surgical management.
AB  - BACKGROUND: Petroclival meningiomas represent a difficult surgical challenge. The
      introduction of modern techniques of skull base surgery has stimulated the
      interest of the neurosurgical community in the surgical management of these
      lesions, although very good results have been obtained by experienced
      neurosurgeons in cases of petroclival meningioma operated using traditional
      surgical approaches. METHODS: Thirty-one cases of petroclival meningioma have
      been operated on during a 4-year period using two different philosophies as far
      as the approach. Group A patients (13 cases) have been operated on using mostly
      either a subtemporal transtentorial or a retrosigmoid approach. Group B patients
      (18 cases) have been managed using a lateral skull base approach, either the
      anterior transpetrosal or the presigmoid approach.
      Translabyrinthine/transcochlear approaches have been used occasionally. RESULTS:
      Tumor dissection and removal seemed to be easier in skull-base operated patients.
      However, operations take longer and surgical complications such as cerebrospinal
      fluid leak and hearing loss were increased. Radical tumor removal could be
      achieved in an equal percentage of cases of both groups (77% vs. 83%). The early
      postoperative course was more favorable in group B patients. However, late
      permanent morbidity appeared to be similar in the two groups of patients.
      CONCLUSIONS: Skull base approaches facilitate tumor dissection and removal at the
      expense of increased surgical complications. However, the widened surgical field
      and increased angle of approach that the techniques of skull base surgery may
      offer can play a significant role in the removal of sizeable, infiltrative,
      and/or recurrent petroclival meningiomas.

PMID- 10199297
TI  - Vertebral osteoblastoma: are radiologic structural changes necessary for
      diagnosis?
AB  - BACKGROUND: A case of osteoblastoma localized at the pedicle of the 10th thoracic
      vertebra is presented. CASE DESCRIPTION: The patient complained of nocturnal back
      pain not relieved by salycilates, a typical symptom of osteoblastoma. Bone
      scintigraphy showed a lower thoracic focus of increased osteoblastic activity;
      however, X-rays, computed tomography, and magnetic resonance images (MRI) were
      within normal limits, showing only obscure changes that were also noted in the
      rest of the spine. Repeat MRI with contrast revealed a focal enhancement. After
      pediculectomy, histopathologic examination confirmed the diagnosis of
      osteoblastoma. Fifteen months postoperatively, the patient is symptom-free.
      CONCLUSION: Our case demonstrates that some cases of osteoblastoma may not have
      the classical radiological appearance. Although non-contrast computed tomography
      and T1-weighted MRI are mildly positive in some instances, osteoblastoma is best
      visualized on MRI with gadolinium. Like any other neoplasm, osteoblastoma should
      be detected and removed early, before it can cause structural bony changes.

PMID- 10199298
TI  - Intraventricular hemorrhage as a false localizing sign of a thoracolumbar
      arteriovenous malformation: case report.
AB  - BACKGROUND: Spinal arteriovenous malformation (SAVM) is a relatively rare disease
      characterized by a high incidence of intramedullary and subarachnoid haemorrhage.
      When the hemorrhage is profuse and the SAVM is in the cervical region the
      symptoms (disturbance of consciousness, papilledema, cranial nerve palsies, and
      convulsions) may be so severe and rapid in their onset that they may be mistaken
      for intracranial hemorrhage. We report here on a patient with a SAVM at T10-12,
      which bled intracranially, mainly intraventricularly, and resulted first in
      respiratory arrest and unconsciousness. CASE DESCRIPTION: The patient had been
      well until he was 28 years old when, during intercourse, he suffered a terrible
      headache and suddenly lost consciousness, with a transient respiratory arrest. He
      was also noted to have right hemiparesis. A computed tomography scan demonstrated
      intraventricular hemorrhage. After a 24-hour period of artificial ventilation the
      patient regained consciousness and the right arm paresis completely recovered,
      but a gradual worsening of the motor function of the left leg developed. Digital
      subtraction angiography did not demonstrate any intracranial source of bleeding,
      whereas spinal angiography revealed a SAVM located at the medullary cone, which
      was totally removed by surgery. CONCLUSION: The case reported here raises several
      important issues. First, the advisability of spinal magnetic resonance imaging in
      the investigation of intraventricular (and subarachnoid) hemorrhage in patients
      with no demonstrable intracranial source. Secondly, the benefits of early
      diagnosis and reestablishment of the spinal cord circulation before the onset of
      thrombosis and the progressive phase of myelopathy. Finally, the necessity of
      complete obliteration and treatment of SAVMs even in patients with fixed
      neurologic deficits, because rebleeding of lower thoracic or lumbar SAVMs can
      lead to impairment at a higher level with severe or lethal consequences.

PMID- 10199299
TI  - Intramedullary cavernous angioma. Resection by oblique corpectomy.
AB  - BACKGROUND: Intramedullary cavernomas are rare lesions usually operated on via a
      posterior approach and myelotomy. CASE REPORT: A 42-year-old woman progressively
      developed a tetraplegia with sphincter disturbances over a period of 26 years.
      Magnetic resonance imaging showed a cervical intramedullary cavernoma with an
      extramedullary anterolateral exophytic portion. To avoid myelotomy, this lesion
      was approached directly via its anterior exophytic portion. Through a cervical
      anterolateral approach, the vertebral body of C4 and the intervertebral discs
      were obliquely drilled out. The posterior longitudinal ligament and the dura
      mater were opened. The exophytic portion was coagulated and the intramedullary
      portion was completely excised. The dura mater was closed and a bone graft was
      inserted between C3 and C5 and secured with a plate. RESULTS: After transient
      worsening, upper limb weakness improved from its preoperative status but
      paraparesis persisted after a follow-up of 12 months. The sphincter disturbances
      disappeared. CONCLUSIONS: The anterolateral approach combined with oblique
      corpectomy may be an appropriate technique in case of anterior intramedullary
      cavernomas. It provides direct access to the lesion, avoiding additional
      myelotomy.

PMID- 10199300
TI  - Role of stereotactic aspiration in the management of tuberculous brain abscess.
AB  - BACKGROUND: Intracranial tuberculous abscesses are uncommon clinical entities,
      even in countries where tuberculosis is endemic. Surgical excision and
      antituberculous treatment is the treatment of choice. The role of stereotactic
      aspiration in the management of these lesions is highlighted in this
      communication. METHODS: Three patients, all receiving treatment for pulmonary
      tuberculosis, presented with symptoms of raised intracranial pressure and
      neurological deficits. Computed tomography (CT) scans revealed cystic lesions
      with enhancing rim in the thalamus in two patients and multiple coalescing cystic
      lesions in the deep temporal region in another. RESULTS: Stereotactic aspiration
      of the cyst and biopsy of the cyst wall were performed in all. In two, the pus
      revealed acid fast bacilli (AFB). In another, though the pus did not reveal any
      AFB, the wall showed tuberculous granuloma. Antituberculous treatment was
      continued in all the patients. Follow-up CT revealed resolution of the lesions in
      all patients. CONCLUSION: Stereotactic aspiration is an useful alternative
      modality of management of tuberculous abscesses in a selected group of patients.

PMID- 10199301
TI  - Clostridium perfringens: a rare cause of postoperative spinal surgery meningitis.
AB  - BACKGROUND: Clostridium perfringens is a rare cause of central nervous system
      infections, particularly meningitis. The case of a 76-year-old man who developed
      fatal C. perfringens meningitis after routine decompressive laminectomy for
      spinal stenosis is described. CASE REPORT: Twelve days after surgery the patient
      presented with pain and serosangiunous drainage from the surgical incision site.
      A swab of the drainage revealed Gram-positive bacilli; MRI of the lumbosacral
      spine showed the appearance of air around the laminectomy site. The patient died
      within 6 hours of presentation. Autopsy revealed acute cranial and spinal
      meningitis and choroid plexitis with organisms consistent with C. perfringens.
      CONCLUSION: No significant enteral pathology or source of endogenous infection
      was determined, suggesting postoperative wound contamination and meningeal
      seeding with this ubiquitous organism. Clostridial infection, although rare,
      should be considered in any patient with meningitis with a history of surgical
      intervention. Survival with minimal neurological deficits was achieved in half of
      the previously reported cases.

PMID- 10199302
TI  - Infection rate with replacement of bone fragment in compound depressed skull
      fractures.
AB  - BACKGROUND: Traditional management of compound depressed skull fractures entails
      elevation and removal of all bone fragments with delayed cranioplasty. Bone
      fragment removal is intended to reduce the potential for infection. However, bone
      fragment removal often necessitates a second operation to repair the resultant
      calvarial defect. This study examines the postoperative infection rate when bone
      fragments are replaced primarily. METHODS: A retrospective study was carried out
      of all patients admitted with the diagnosis of compound depressed skull fracture
      to a university hospital from 1991 to 1996. RESULTS: Of 52 patients with the
      diagnosis of compound depressed skull fracture treated at our university hospital
      over the past 5 years, 32 underwent elevation and repair within 72 hours. All
      patients except one received antibiotics during surgery and for at least 1.5 days
      after surgery. Follow-up averaged just over 22 months. In all 32 consecutive
      patients treated with debridement and elevation of compound depressed skull
      fractures with primary replacement of bone fragments within 72 hours of injury,
      there were no infectious sequelae. CONCLUSIONS: Immediate replacement of bone
      fragments in compound depressed skull fractures does not increase the risk of
      infectious complications.

PMID- 10199303
TI  - Nonshaved cranial neurosurgery.
AB  - BACKGROUND: Preoperative shaving for cranial neurosurgical procedures is still
      recommended in textbooks. There are reports demonstrating the success of
      nonshaved surgery. The objective of this study was to compare the surgical
      infection rate of cranial neurosurgical procedures with two different scalp
      preparations: shaved or nonshaved. METHODS: Clinical trials of nonshaved scalp
      preparation were performed in non-emergency cranial neurosurgical procedures at
      Songklanagarind Hospital from August 1994 to December 1996. Patients were entered
      in the nonshaved group using the following exclusion criteria: immunocompromised
      host, presence of infectious diseases, surgery with foreign material insertion,
      multiple operations within 1 month, and presence of traumatic wound around the
      operative site. Patients who survived less than 1 month after surgery were
      excluded except in cases where death resulted from intracranial infection.
      RESULTS: During the 29-month period, 225 of 1,244 cranial neurosurgical
      procedures were selected for study. Ages ranged from 4 to 86 years. Brain tumors
      were encountered in 57%. In the nonshaved group, there were 89 procedures (80
      cases), compared with 136 procedures (123 cases) in the shaved group. Surgical
      infection rates were 3.37% and 5.88%, respectively (p>0.05). CONCLUSIONS:
      Nonshaved scalp preparation is recommended for nonemergency cranial neurosurgical
      procedures.

PMID- 10199304
TI  - A drainage bag (jelly bag) using a superabsorbent polymer: technical note.
AB  - BACKGROUND: Various types of drainage bags for use after an operation are
      currently available, but they are often bulky, and backflow of contents can occur
      when the bag is not in the upright position. METHODS: As an alternative, we
      developed a drainage bag containing a superabsorbent polymer that becomes jelly
      like as it absorbs the fluid. RESULTS: This bag is lightweight and compact for
      easy carrying, and there was no backflow, whatever its position. CONCLUSION:
      These features demonstrate a very useful drainage bag. This bag was remarkably
      useful for unconscious patients or for restless ones, particularly in the field
      of neurosurgery.

PMID- 10199305
TI  - The power of the individual.

PMID- 10199306
TI  - Commendably and with a good conscience.

PMID- 10199307
TI  - Familial patterns of thoracic aortic aneurysms.
AB  - HYPOTHESIS: To provide evidence that genetic factors contribute to the
      development of thoracic aortic aneurysms (TAA) by demonstrating familial patterns
      of the disease. DESIGN: Retrospective review. SETTING: University hospital.
      PATIENTS AND METHODS: We sought to identify familial patterns of TAA from a
      database of 598 patients evaluated or treated for TAA at the Yale Center for
      Thoracic Aortic Disease, New Haven, Conn, from January 1985 to August 1998. Of
      the 598 patients, 45 patients had a diagnosis of Marfan syndrome and 553 patients
      had no known history of any collagen vascular disorder. Of the 553 patients in
      the latter category, 398 patients had confirmed TAA, 66 had TAA with concomitant
      aortic dissections, and 89 had aortic dissections. From the group of 464 patients
      with TAA with or without concomitant aortic dissections, 2 interviewers attempted
      to contact 150 randomly selected patients for telephone screening to determine
      the presence of familial patterns of aortic disease. Fifteen of these patients
      were lost to follow-up. Complete medical and family histories of the remaining
      135 patients (85 men, 50 women) were reviewed. Of the 135 individuals screened,
      26 (18 men, 8 women) (19.3%) were found to belong to multiplex pedigrees. These
      26 patients with familial nonsyndromic TAA were compared with the remaining 109
      patients with sporadic TAA and the 45 patients with Marfan syndrome-associated
      TAA. MAIN OUTCOME MEASURES: Groups were examined for statistical differences in
      age and aortic size at the time of diagnosis, growth rates of TAA, and rates of
      concomitant diseases. Nonsyndromic family pedigrees were analyzed and potential
      modes of inheritance were determined. RESULTS: The mean age at presentation for
      patients with familial nonsyndromic TAA (56.8 years) was significantly younger
      than the mean age of presentation in sporadic cases (64.3 years, P< or =.03), and
      significantly older than that of patients with Marfan syndrome (24.8 years, P< or
      =.001). Patients with a family history of aortic aneurysms had faster growth
      rates (0.22 cm/y) compared with patients with sporadic TAA (0.03 cm/y) (P< or
      =.001) and patients with Marfan syndrome (0.10 cm/y) (P< or =.04). Familial
      nonsyndromic TAA in patients with a concomitant aortic dissection had a growth
      rate of 0.33 cm/y, which was greater than that of patients with sporadic TAA
      (0.10 cm/y) and patients with Marfan syndrome (0.08 cm/y) with associated aortic
      dissection. This growth of 0.33 cm/y was significantly faster than the overall
      growth rate estimate of aneurysms in patients with aortic dissection (0.14 cm/y)
      (P< or =.05). Ten pedigrees (38.5%) showed direct father to son transmission,
      consistent with an autosomal dominant mode of inheritance. Six family pedigrees
      (23.1%) suggested an autosomal dominant or X-linked mode of inheritance. Seven
      pedigrees (26.9%) suggested a recessive mode of inheritance; 2 an autosomal
      recessive mode, and 5 an X-linked recessive or autosomal recessive mode. The
      remaining 3 pedigrees displayed more complex modes of inheritance. CONCLUSIONS:
      This study supports the role of genetic factors influencing familial aggregation
      of TAA. Thoracic aortic aneurysms in association with multiplex pedigrees
      represent a new risk factor for aneurysm growth. Pedigree analysis suggests
      genetic heterogeneity. The primary mode of inheritance seems to be autosomal
      dominant, but X-linked dominant and recessive modes are also evident.

PMID- 10199308
TI  - Does uninjured skin release proinflammatory cytokines following trauma and
      hemorrhage?
AB  - HYPOTHESIS: Uninjured skin contributes to the elevation in circulating levels of
      proinflammatory cytokines seen following severe injury. DESIGN: Male C3H/HeN mice
      underwent trauma, trauma-hemorrhage and resuscitation, or closed long-bone
      fracture. Serum, skin, and liver samples were harvested at designated times after
      experimental treatment. MAIN OUTCOME MEASURES: Levels of interleukin (IL) 1beta,
      IL-6, and tumor necrosis factor alpha (TNF-alpha) were determined in serum and
      skin cultures at 1, 8, and 24 hours after trauma-hemorrhage. The RNA was isolated
      from liver and skin samples at 1, 2, 4, 8, and 24 hours from all 3 experimental
      groups, and gene expression of the cytokines was determined. RESULTS: Remote
      (nontraumatized) skin from trauma-hemorrhage animals released significantly more
      IL-6 and TNF-alpha into culture supernatants at 1 and 24 hours and significantly
      more IL-1beta at 1, 8, and 24 hours than did skin from sham animals. Serum levels
      of all 3 cytokines were significantly elevated at 1 and 24 hours after trauma
      hemorrhage relative to sham animals. Gene expression of all 3 cytokines was
      detected in skin and liver following trauma-hemorrhage. Furthermore, gene
      expression of all 3 cytokines was detected in uninjured skin after soft tissue
      trauma and closed long-bone fracture. CONCLUSIONS: Proinflammatory cytokine gene
      expression is up-regulated in uninjured skin following trauma, trauma-hemorrhage,
      and long-bone fracture. This increase in gene expression correlates with
      increased cytokine production by cultured skin as well as increased circulating
      cytokine levels. These results suggest that uninjured skin may also contribute to
      the rise in circulating cytokine levels seen after injury.

PMID- 10199309
TI  - Extracorporeal membrane oxygenation for nonneonatal acute respiratory failure.
AB  - HYPOTHESIS: Extracorporeal membrane oxygenation (ECMO) is effective in
      nonneonatal acute respiratory failure under certain circumstances. DESIGN:
      Retrospective medical record review. SETTING: The intensive care unit of a
      tertiary care hospital. PATIENTS: Thirty-four nonneonatal patients (mean age, 22
      years; range, 8 days to 56 years), with ratios of the PaO2 to the fraction of
      inspired oxygen persistently below 70, who were treated with ECMO after maximal
      ventilator therapy had failed (mean time of ventilator therapy, 6.9 days; range,
      1-41 days). The mean ECMO duration was 304 hours (range, 56-934 hours). Patients
      were grouped into 7 categories based on their diagnosis: sepsis or sepsis
      syndrome (n = 3), bacterial or fungal pneumonia (n = 10), viral pneumonia (n =
      5), trauma or burn (n = 2), inhalation injury without burn (n = 1),
      immunocompromised state (due to transplantation or chemotherapy) (n = 8), and
      acute respiratory failure of unknown origin (n = 5). MAIN OUTCOME MEASURE:
      Survival to hospital discharge following ECMO therapy. RESULTS: Overall survival
      was 53% (18 patients). All 6 patients (100%) with viral pneumonias or isolated
      inhalation injuries survived. Of 13 patients with bacterial pneumonia, sepsis, or
      sepsis syndrome not complicated by multiorgan failure, 10 (77%) survived. In
      contrast, all but 1 of the immunocompromised patients died. Survival in patients
      who were intubated for less than 9 days before ECMO was 64%, whereas survival
      fell precipitously to 22% for patients who experienced mechanical ventilation for
      9 or more days before the implementation of ECMO. Finally, the proportion of
      patients who died while receiving ECMO therapy was greater when the ECMO duration
      exceeded 300 hours (62% vs. 38%; P<.05). CONCLUSIONS: Nonneonatal survival with
      ECMO therapy is strongly dependent on the diagnosis. Pre-ECMO intubation for less
      than 9 days had little effect on survival. Survival rates decreased when the
      length of time of receiving ECMO exceeded 300 hours.

PMID- 10199310
TI  - Outcome of patients with melanoma and histologically negative sentinel lymph
      nodes.
AB  - HYPOTHESIS: Patients with melanoma and histologically negative sentinel lymph
      nodes identified by lymphatic mapping have a very good prognosis. DESIGN: Cohort
      study with follow-up information obtained from medical records and telephone
      interviews. SETTING AND PATIENTS: Of all patients with cutaneous melanoma who
      underwent intraoperative sentinel lymph node mapping between November 15, 1993,
      and April 18, 1997, at the Massachusetts General Hospital, Boston, 89 were found
      to have no evidence of melanoma in their sentinel nodes. Forty-six lesions (51%)
      were on an extremity and 44 (49%) were of axial location. The median tumor
      thickness was 1.8 mm (range, 0.36-12.0 mm) and 11 tumors (12%) were ulcerated.
      INTERVENTIONS: Patients underwent intraoperative sentinel lymph node mapping with
      lymphazurin and radiolabeled sulfur colloid. Sentinel lymph nodes were analyzed
      by standard hematoxylin-eosin staining. Only 2 patients received adjuvant therapy
      following wide excision of the primary lesion. MAIN OUTCOME MEASURES: Site of
      initial recurrence and time to initial recurrence. RESULTS: The median follow-up
      for all patients was 23 months (range, 2-54 months). Eleven patients (12%)
      developed melanoma recurrences, and 78 (88%) patients remain disease free.
      Regional lymph nodes were the initial site of recurrence in 7 (8%) of 89
      patients, and 7 (7%) of 106 mapped basins. Four patients had recurrence without
      involvement of regional lymph nodes: 2 with distant metastases and 2 with in
      transit metastases. The median time to recurrence was 12 months (range, 2-35
      months). Sentinel lymph nodes were reanalyzed using serial sections and
      immunoperoxidase stains in 7 patients with recurrence and metastatic melanoma was
      identified in 3 (43%). CONCLUSIONS: The risk for melanoma recurrence is
      relatively low in patients with histologically negative sentinel nodes identified
      by lymphatic mapping. Longer follow-up will improve our understanding of the
      prognostic value of this procedure.

PMID- 10199311
TI  - Multimodality management of Merkel cell carcinoma.
AB  - HYPOTHESIS: Merkel cell carcinoma is a rare dermal neuroendocrine carcinoma whose
      optimal treatment and prognostic factors are poorly defined. We hypothesize that
      high-risk patients with Merkel cell carcinoma are best treated with multimodality
      therapy. DESIGN: A retrospective review of all patients (N = 33) with Merkel cell
      carcinoma treated at the Massachusetts General Hospital from January 1, 1980, to
      August 24,1997. Median follow-up time was 37 months (range, 6-157 months).
      PATIENTS: Adequate data for evaluation were available for 31 patients. Male to
      female distribution was 14 men and 17 women, with a median patient age of 68
      years. MAIN OUTCOME MEASURE: Stage at presentation; factors associated with
      recurrence; and the effects of surgery, radiation therapy (XRT), and chemotherapy
      on recurrence, salvage, and survival rates. RESULTS: There were 12 extremity, 11
      head and neck, and 8 truncal tumors. There were 22 isolated primary tumors, 8
      with additional clinically positive lymph nodes, and 1 with distant disease.
      Therapy was local excision with or without XRT in 19 patients, local resection
      and lymphadenectomy with or without XRT in 8 patients, and XRT alone in 4
      patients with head and neck tumors. Fifteen patients developed recurrences (7
      local, 8 nodal, and 10 distant). Median time to recurrence was 8 months (range, 3
      48 months). There were 7 tumor-related deaths, 6 of which were associated with
      truncal lesions (P<.001). No locoregional recurrences occurred in patients with
      margins of resection of 2 cm or greater or adequate XRT. A multivariate analysis
      selected truncal location (P = .005) and nodal disease (P = .05) as predictors of
      mortality. Remission was possible in 5 patients with locoregional and 2 patients
      with distant recurrences. CONCLUSIONS: Merkel cell carcinoma is an aggressive
      dermal cancer with frequent nodal metastases; truncal tumors have the worst
      prognosis. Locoregional recurrence correlates with inadequate margins and lack of
      XRT, but remission is possible with multimodality therapy.

PMID- 10199312
TI  - Mechanism of adrenal insufficiency following trauma and severe hemorrhage: role
      of hepatic 11beta-hydroxysteroid dehydrogenase.
AB  - BACKGROUND: Although adrenal insufficiency may not occur with moderate
      hypotension, it does occur with severe hemorrhage. Since hepatocellular function
      is depressed following severe hemorrhage, it remains unknown whether the liver
      plays any role in regulating adrenal function after trauma and hemorrhagic shock.
      HYPOTHESIS: Hepatic 11beta-hydroxysteroid dehydrogenase (11beta-HSD), a
      microsomal enzyme responsible for the degradation of bioactive corticosterone,
      plays a major role in the development of adrenal insufficiency following trauma
      and severe hemorrhage. DESIGN, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Male
      rats underwent laparotomy to induce trauma before hemorrhage. They were then bled
      to and maintained at a blood pressure of 40 mm Hg until 40% of the maximal bleed
      out volume was returned in the form of Ringer lactate. The rats were then
      resuscitated with 4 times the volume of maximal bleed-out with Ringer lactate
      during a 60-minute period. Plasma levels of corticosterone and corticotropin were
      measured at various intervals. In additional groups, corticotropin-induced
      corticosterone release, adrenal contents of corticosterone and cyclic adenosine
      monophosphate (cAMP), hepatic 11beta-HSD activity, and plasma levels of
      corticosterone-binding globulin were determined at 1.5 hours after resuscitation.
      Moreover, a model of moderate hypotension (blood pressure, 80 mm Hg) was used to
      determine whether adrenal function is depressed under such conditions. RESULTS:
      At the time of maximal bleed-out, plasma corticosterone and corticotropin levels
      increased by 245% (P<.001) and 293% (P<.001), respectively. Despite corticotropin
      levels being similar to those of the animals undergoing sham operation after
      resuscitation, corticosterone levels in hemorrhaged animals remained elevated up
      to 4 hours after resuscitation (by 158%-207%; P<.001). In addition, corticotropin
      induced corticosterone release decreased by 78% at 1.5 hours after resuscitation
      (P = .009). In contrast, moderate hypotension did not reduce corticotropin
      induced corticosterone release. Adrenal corticosterone content and cAMP levels
      (i.e., the second messenger of corticotropin action) decreased by 55% (P<.001)
      and 25% (P = .03), respectively. Hepatic 11beta-HSD activity decreased
      significantly at 1.5 hours after resuscitation (P<.001). CONCLUSIONS: Sustained
      increase in plasma corticosterone levels following hemorrhage and resuscitation
      may be, in part, due to the decreased hepatic 11beta-HSD activity. The high level
      of corticosterone negatively regulates corticotropin release, further reducing
      adrenal responsiveness to corticotropin stimulation. Thus, the liver appears to
      play an important role in regulating adrenal function following trauma and severe
      hemorrhage.

PMID- 10199313
TI  - Interval or permanent nonoperative management of acute type A aortic dissection.
AB  - HYPOTHESIS: Selected patients with acute type A (ascending) aortic dissection who
      are treated with delayed operation or nonoperative therapy may have better early
      and short-term outcomes than was previously expected. DESIGN AND SETTING:
      Retrospective cohort at a university hospital. SUBJECTS: Data on 75 patients with
      acute or chronic type A aortic dissection treated at one institution from January
      1, 1985, to November 30, 1997, were analyzed. Of these 75 patients, 34 (21 male
      and 13 female, with a mean age of 65.5 years) did not undergo initial operative
      treatment, and 15 (10 male and 5 female, with a mean age of 72.6 years) never
      underwent surgery. For the 19 patients who underwent delayed surgery, the mean
      period between aortic dissection and intervention was 11.4+/-4.83 days. The
      follow-up period ranged from 0.27 to 149 months, with a mean of 20.2 months. MAIN
      OUTCOME MEASURES: Vascular complications, hospital mortality, and early survival.
      RESULTS: Reasons for interval delay in surgical treatment included initial
      misdiagnosis or delay in diagnosis (13 [68%] of 19), need to address significant
      comorbidity (4 [21%] of 19), and initial refusal of operative intervention (2
      [11%] of 19). For the 15 patients treated entirely by medical therapy, reasons
      for electing nonoperative management included extensive comorbidity (5 [33%] of
      15), refusal of surgical intervention (6 [40%] of 15), and misdiagnosis or long
      delay in diagnosis (4 [27%] of 15). Of the 34 patients, 15 (44%) presented with
      moderate or severe aortic insufficiency, 5 (14%) had evidence of pericardial
      effusion, 6 (21%) had evidence of concomitant coronary ischemia on
      electrocardiogram, and 8 (24%) had extension of the dissection into the
      descending aorta. Four patients (11.8%) died while in the hospital. Of the 34
      patients, 30 (88%) who underwent either delayed or no surgery received aggressive
      medical treatment (beta-adrenergic blocking agents and afterload-reducing agents)
      and were discharged from the hospital. All patients who were operative candidates
      in the interval treatment group survived to reach definitive operation. There was
      no statistically significant difference in short-term survival between the group
      of patients undergoing delayed surgery or medical treatment only and the group of
      41 patients undergoing early operation (P = .42). CONCLUSIONS: Immediate surgical
      therapy is still recommended for acceptable operative candidates with acute type
      A aortic dissection who seek immediate treatment. However, this study permits the
      following 2 conclusions: (1) patients with type A aortic dissection who are
      referred or whose conditions are diagnosed several days after presentation have
      survived the early dangerous period and can safely undergo surgery semielectively
      (rather than emergently); and (2) selected patients who are not considered
      operative candidates and who survive the initial type A aortic dissection without
      complication may be treated with aggressive medical therapy and achieve
      acceptable early and short-term outcomes, which is better than previously
      expected.

PMID- 10199314
TI  - Cavernous hemangioma of the liver: anatomic resection vs. enucleation.
AB  - HYPOTHESIS: Patient outcome and the development of major intra-abdominal
      postoperative complications following removal of cavernous hemangiomas of the
      liver are affected by methods of resection. DESIGN: Case-control study. SETTING:
      Hepatobiliary surgery and liver transplantation unit in a tertiary care referral
      medical center. PATIENTS: Between December 1, 1987, and December 1, 1997, 28
      patients underwent the surgical removal of cavernous hemangioma either by hepatic
      resection or enucleation. Indications for the operation were pain, enlarging
      tumors, uncertain diagnosis, or rupture. MAIN OUTCOME MEASURES: The technique of
      tumor removal, hospital course, and the development of intra-abdominal
      complications. Independent factors influencing the development of complications
      were ascertained by multivariate analysis. RESULTS: Twenty-four female and 4 male
      patients (age, 47.5+/-12.4 [mean +/- SD] years) underwent either enucleation (n =
      23) or liver resection (n = 5). Lesions ranged from 2 to 16 cm in their
      postresection diameter. No surgical (30-day) mortality was observed. Four major
      intra-abdominal complications were found: 1 episode of intraoperative bleeding
      requiring abdominal packing and 3 intra-abdominal fluid collections requiring
      percutaneous drainage. Enucleation was the only independent factor found by
      univariate and multivariate analyses to be associated with a reduction in the
      number of intra-abdominal complications (P = .04). CONCLUSIONS: Cavernous
      hemangiomas of the liver can be removed safely by either hepatic resection or
      enucleation. Enucleation is associated with fewer intra-abdominal complications
      and should be the technique of choice when tumor location and technical factors
      favor enucleation.

PMID- 10199315
TI  - Perioperative strokes after 1001 consecutive carotid endarterectomy procedures
      without an electroencephalogram: incidence, mechanism, and recovery.
AB  - HYPOTHESIS: That alternative methods of cerebral protection, especially routine
      shunting of all patients undergoing general anesthesia or shunting on the basis
      of neurologic assessment with the patient awake under cervical plexus block,
      result in outcomes of carotid endarterectomy comparable with those reported using
      electroencephalographic monitoring. DESIGN: Retrospective review of cases from a
      vascular registry established in 1990. SETTING: Tertiary care center. PATIENTS:
      Consecutive sample of 1001 patients who underwent carotid endarterectomy.
      INTERVENTIONS: Carotid endarterectomy procedures were performed without
      electroencephalographic monitoring, using general anesthesia with routine
      shunting or using regional anesthesia. MAIN OUTCOME MEASURES: Overall stroke and
      mortality rates and cause and consequence of the postoperative strokes. RESULTS:
      There were 14 nonfatal strokes (1.4%) and 2 deaths (0.2%), for a combined stroke
      and death rate of 1.6%. Nine (64%) of the 14 strokes appeared to result from a
      technical error during the endarterectomy. Mild deficits were noted after 7
      strokes (50%), with the remainder resulting in deficits that required inpatient
      rehabilitation. Twelve patients with strokes (86%) eventually returned home
      without need for assistance. CONCLUSIONS: Most postoperative strokes in this
      series were due to technical errors. Overall, even in patients with strokes
      initially requiring inpatient rehabilitation, there was good recovery of
      function. Low stroke and mortality rates can be achieved in carotid
      endarterectomy without the use of electroencephalographic monitoring.

PMID- 10199316
TI  - Distal splenorenal shunt: role, indications, and utility in the era of liver
      transplantation.
AB  - HYPOTHESIS: The distal splenorenal shunt (DSRS) continues to play an important
      role in the management of recurrent variceal bleeding with minimal negative
      impact on subsequent orthotopic liver transplantation (OLT). DESIGN: Case-control
      study. SETTING: Hepatobiliary surgery and liver transplantation unit in a
      tertiary referral medical center. PATIENTS: From August 1, 1985, through October
      31, 1997, a single team of surgeons performed 81 DSRS procedures for recurrent
      variceal hemorrhage. Eleven patients undergoing OLT subsequent to DSRS were
      compared with a group of 274 patients undergoing OLT without any previous shunt
      during the same period. MAIN OUTCOME MEASURES: Operative time, use of blood
      products, length of hospital stay, perioperative complications, and survival
      rates. RESULTS: Operative (30-day) mortality for DSRS was 6% (n = 5). From follow
      up information available for 74 patients, the 1- and 5-year survival rates were
      86.4% (n = 64) and 74.3% (n = 55), respectively. Recurrent variceal bleeding and
      hepatic encephalopathy occurred in 5 (6.8%) and 11 patients (14.9%),
      respectively, after DSRS. In 9 patients, DSRS was used as salvage for failed
      transjugular intrahepatic portosystemic shunt. CONCLUSIONS: Distal splenorenal
      shunt is a safe, durable, and effective treatment for controlling recurrent
      variceal hemorrhage in patients with acceptable operative risk and good liver
      function. It does not compromise future liver transplantation and can
      considerably delay the time until transplantation is required. Given the early
      occlusion rate and need for constant surveillance, transjugular intrahepatic
      portosystemic shunting should be reserved for patients with Child C
      classification cirrhosis with chronic hemorrhage or intractable ascites or as an
      emergency procedure for patients with uncontrollable bleeding using endoscopic
      therapy.

PMID- 10199317
TI  - Reticuloendothelial system activity and organ failure in patients with multiple
      injuries.
AB  - HYPOTHESIS: Reticuloendothelial system function is altered in patients with
      multiple trauma and organ failure. DESIGN: Prospective cohort study. SETTING:
      Surgical intensive care unit at a level I trauma center. PATIENTS: Patients with
      multiple blunt trauma and injury severity scores greater than 20, with no
      referrals. INTERVENTIONS: Every second day reticuloendothelial system (RES)
      clearance capacity and liver blood flow were determined by administering labeled
      human albumin. Liver function was measured by enzymatic decay of indocyanine
      green, and levels of plasma tumor necrosis factor alpha were evaluated. RESULTS:
      In nonsurviving patients with blunt trauma, RES function was altered and was
      associated with organ dysfunction and infectious complications. Of 61 patients,
      42 survived and 19 did not. Sixteen patients (84%) died of multiple organ
      failure. Significantly elevated RES activity (colloid clearance rate) was present
      between day 5 and day 13 after trauma in nonsurvivors (0.86+/-0.16 [mean +/- SD]
      on day 7, P = .003) compared with survivors (0.48+/-0.08 on day 7) and 20 healthy
      volunteers (0.47+/-0.06); RES activity then decreased to subnormal levels in
      nonsurvivors. Tumor necrosis factor alpha plasma levels were elevated early after
      injury only in nonsurvivors (on day 1: nonsurvivors, 1.2+/-0.4 ng/mL [mean +/-
      SD]; survivors, 0.5+/-0.2 ng/mL; P = .02). Indocyanine green half-life values
      increased late after trauma, indicating late organ failure (on day 19:
      nonsurvivors, 111+/-29 minutes [mean +/- SD]; survivors, 12+/-4 minutes; P<.001).
      CONCLUSIONS: Early after trauma, nonsurviving patients demonstrated increased
      proinflammatory cytokine levels, followed by a state of pathological
      hyperactivation of the reticuloendothelial system prior to death. These results
      indicate that the stationary host defense system is involved in the mechanisms
      causing organ failure after severe trauma.

PMID- 10199319
TI  - Clinical implications of hemoglobin as a nitric oxide carrier.
AB  - Hemoglobin is perhaps the most intensively studied of the biologically important
      molecules. Much is known of its structure, its function, and its regulation. In
      addition to well-characterized processes of oxygen, carbon dioxide, and carbon
      monoxide transport, new data suggest a key role of hemoglobin as a carrier of
      nitric oxide. In this review, we describe the basis of this interaction, as well
      as its clinical relevance to such problems as acute respiratory distress
      syndrome, percutaneous transluminal coronary angioplasty, and transplant
      allograft survival.

PMID- 10199318
TI  - Perioperative immunonutrition in patients undergoing cancer surgery: results of a
      randomized double-blind phase 3 trial.
AB  - HYPOTHESIS: Perioperative administration of a supplemented enteral formula may
      reduce the rate of postoperative infections. DESIGN: Prospective, randomized,
      double-blind clinical trial. SETTING: Department of surgery at a university
      hospital. PATIENTS: Two hundred six patients with neoplasm of colorectum,
      stomach, or pancreas. INTERVENTION: Patients were randomized to drink 1 L/d of
      either a control enteral formula (n = 104) or the same formula enriched with
      arginine, RNA, and omega3 fatty acids (n = 102) for 7 consecutive days before
      surgery. The 2 diets were isoenergetic and isonitrogenous. Jejunal infusion with
      the same formulas was started 6 hours after operation and continued until
      postoperative day 7. MAIN OUTCOME MEASURES: Rate of postoperative infectious
      complications and length of hospital stay. RESULTS: Both groups were comparable
      for age, sex, weight loss, Karnofsky scale score, nutritional status, hemoglobin
      level, duration of surgery, blood loss, and rate of homologous transfusion.
      Intent-to-treat analysis showed a 14% (14/102) infectious complication rate in
      the supplemented group vs 30% (31/104) in the control group (P = .009). In the
      eligible population, the postoperative infection rate was 11% (9/85) in the
      supplemented group vs. 24% (21/86) in the control group (P = .02). The mean +/-
      SD length of postoperative stay was 11.1+/-4.4 days in the supplemented group and
      12.9+/-4.6 in the control group (P = .01). CONCLUSION: Perioperative
      administration of a supplemented enteral formula significantly reduced
      postoperative infections and length of stay in patients undergoing surgery for
      cancer.

PMID- 10199320
TI  - Surgery in Argentina.
AB  - This article will provide a brief background on Argentina and then summarize the
      country's medical and surgical history, undergraduate and postgraduate training
      programs, residency programs, surgical associations, research, and the
      Argentinean Journal of Surgery (Revista Argentina de Cirugia). Surgery in
      Argentina is at the same level as that of most developed countries although
      transplantation, traumatology, and laparoscopic surgery have been emphasized.

PMID- 10199321
TI  - The value of physician assistants to surgical education in teaching hospitals.

PMID- 10199322
TI  - An update of tumor metastasis to the breast data.

PMID- 10199323
TI  - From tennis courts to transplants.

PMID- 10199324
TI  - Medical education in early 19th century America.

PMID- 10199325
TI  - Neuro-oncology 1999.

PMID- 10199326
TI  - Neuro-oncology: an overview.
AB  - The direct, indirect, and treatment-related effects of cancer on the nervous
      system have received variable attention by neurologists over the past century.
      The diseases encompassed in the neuro-oncology field and our understanding of
      them have increased rapidly during the past 30 years. In part, progress has been
      driven by technological achievements in neuroimaging, in particular, computed
      tomography and magnetic resonance imaging. These advances have allowed
      unprecedented opportunities to view the anatomy and pathology of the central
      nervous system (CNS) and, to an extent, portions of the peripheral nervous system
      that could be affected by cancer or its treatment. Clear gains have occurred in
      diagnostic accuracy, neurosurgical safety, ease of tumor resection, and safer and
      more accurate radiotherapy. After carmustine chemotherapy was introduced in the
      late 1960s, neurosurgeons and a new breed of physician, the neuro-oncologist,
      investigated the clinical benefits of an increasing number of anticancer agents
      against gliomas, medulloblastomas, and metastatic tumors in the CNS. In parallel,
      another sector of neuro-oncology developed that was more closely allied with
      neurology. The focus of this activity was in correlative neurology and pain
      management issues.

PMID- 10199327
TI  - Paraneoplastic syndromes.
AB  - The fact that a small cancer hidden in the chest, abdomen, or pelvis could
      destroy or damage portions of the nervous system, such as cerebellar Purkinje
      cells or cholinergic synapses, has intrigued neurologists since paraneoplastic
      syndromes were first described. In 1965, when little was known about their
      pathogenesis, a full issue of the journal Brain and an international symposium
      were devoted to paraneoplastic disorders. In this decade, the discovery of
      several paraneoplastic antibodies that react with both the nervous system and the
      causal cancer has rekindled interest in these syndromes (Table). Several other
      factors make these rare syndromes of clinical and scientific interest. A recent
      review by Dalmau and Posner contains a more comprehensive bibliography of
      paraneoplastic syndromes.

PMID- 10199328
TI  - Advances in cancer pain.
AB  - Advances in cancer pain research and management are an example of the advances
      that have occurred within the field of neuro-oncology, the medical discipline
      that includes the diagnosis and treatment of primary central nervous system
      neoplasms, metastatic and nonmetastatic neurological complications of cancer
      originating outside the nervous system, and pain associated with cancer. Progress
      in the diagnosis and treatment of cancer, coupled with advances in our
      understanding of the anatomy, physiology, pharmacology, and psychology of pain
      perception, has led to improved care of the patient with pain of malignant
      origin. Currently, specialized methods of cancer diagnosis and treatment provide
      the most direct approach to treating cancer pain by treating the cause of the
      pain. Yet, before the introduction of successful antitumor therapy, when
      treatment of the cause of the pain has failed or when injury to bone, soft
      tissue, or nerve has occurred as a result of therapy, appropriate pain management
      is essential.

PMID- 10199329
TI  - Brain tumors in children.
AB  - Childhood brain tumors are the leading cause of cancer-related morbidity and
      mortality in the pediatric years and differ from primary central nervous system
      tumors occurring in adults. Management strategies must take into account not only
      the tumor type, but the age of the patient and the likelihood of treatment
      induced nervous system damage. With current means of treatment, most children
      older than 3 years can be effectively treated. Chemotherapy has taken on an
      increasing role in the treatment of childhood medulloblastomas, low-grade
      gliomas, and high-grade gliomas. Some tumor types, especially atypical teratoid
      tumors, brainstem gliomas, malignant gliomas, and malignant infantile tumors,
      remain significant therapeutic dilemmas.

PMID- 10199330
TI  - Current therapy for brain tumors: back to the future.
AB  - In the last 30 years, while considerable progress has been made in laboratory
      research of malignant gliomas, fewer clinical breakthroughs can be highlighted.
      Laboratory research has improved our understanding of the biology, and especially
      the molecular genetics of this disease. Unfortunately, these successes highlight
      the difficulties in translating laboratory results into substantive clinical
      improvements. In part, these difficulties stem from a schizophrenic view of the
      development and evolution of brain tumors. We believe either that (1) brain
      tumors are local and therefore the most important research should have as its
      goal local control, or (2) brain tumors are diffuse, which is to say that the
      cells rapidly grow beyond their initial locus, and our research goal is the
      prevention or treatment of the advancing tumor front. Clearly both hypotheses
      have merit and, in fact, almost certainly, both are true. The question becomes,
      should we devote our research energies to one hypothesis at the exclusion of the
      other?

PMID- 10199331
TI  - Current treatment of oligodendrogliomas.

PMID- 10199332
TI  - Molecular genetics of brain tumors.
AB  - As many as 40000 patients are newly diagnosed each year as having brain tumors.
      About half of these are metastatic foci of tumors originating outside the central
      nervous system, while the other half are primary tumors of central nervous system
      tissues. These are a diverse group of neoplasms. Currently, primary brain tumors
      are classified in a manner that reflects their histological appearance and
      location. The identification of cancer as a disorder of genes, however, has
      opened the possibility of classifying tumors according to the genetic alterations
      that underlie their pathogenesis and that regulate their malignant behavior. Two
      major classes of genes critical for the development of all types of cancer,
      including brain tumors, are now recognized: tumor suppressor genes, which encode
      genes that function to inhibit cell proliferation and tumor development, and
      oncogenes, which encode proteins that stimulate proliferation and mediate
      biological activities important for invasion, neoangiogenesis, immune escape, and
      other characteristics of malignancy. While in most cases the specific pathways
      regulating tumor characteristics such as tumor neoangiogenesis and tissue
      invasion remain to be defined, recognition of the genetic changes characteristic
      of individual tumor types should provide opportunities to develop more effective,
      less toxic therapies.

PMID- 10199334
TI  - New molecular strategies to cure brain tumors.
AB  - Overall, malignant primary and metastatic brain tumors remain as lethal in the
      1990s as they were in the 1970s. Just as the introduction of radiation therapy 2
      decades ago added several months to survival time, numerous chemotherapeutic
      trials have demonstrated only limited efficacy. Fortunately, recent discoveries
      in molecular medicine have not only revolutionized our understanding of the
      events that lead to tumorigenesis, but they have created novel tools for
      targeting malignant cells. Novel treatment modalities are now being tested in pre
      phase I animal models, while others are in different stages of clinical trials.
      The purpose of this review is to briefly summarize the emerging strategies of
      gene therapy, antiangiogenesis, immunotherapy, and targeting tumor cells.

PMID- 10199333
TI  - Targeting in gene therapy for gliomas.
AB  - Cancer is a disease of a series of genes. Thus, theoretically, brain tumors could
      be treated by targeting their fundamental molecular defects. Currently, most of
      the approved clinical protocols for gene therapy involve cancer patients. Several
      of these protocols are designed to improve the treatment of brain tumors. In this
      brief report, we analyze the rationale, advantages, and disadvantages of a series
      of gene therapy approaches against brain tumors that include transfer of tumor
      suppressor genes and cell-cycle modulators; suicide or prodrug strategies;
      immunogene therapy; antiangiogenesis; and oncolytic virus therapy. In summary, in
      this review, we highlight the translational advances in molecular medicine that
      broaden our battery of therapies for patients with brain tumors.

PMID- 10199335
TI  - TNFA and TNFB polymorphisms in myasthenia gravis.
AB  - BACKGROUND: Tumor necrosis factor (TNF) alpha and TNF-beta are proinflammatory
      cytokines thought to be involved in the pathogenesis of myasthenia gravis (MG).
      OBJECTIVE: To examine whether TNF polymorphisms are associated with MG, MG
      subgroups, and the presence of titin and ryanodine-receptor antibodies. PATIENTS
      AND METHODS: We did genotyping on 30 patients with MG and 92 healthy blood donors
      for 2 biallelic TNFA polymorphisms (G to A at positions -238 and -308) and 1 TNFB
      polymorphism (NcoI digestive site) using methods based on the polymerase chain
      reaction. RESULTS: Patients with thymoma were typically homozygous for both the
      TNFA*T1 and the TNFB*2 alleles, but patients having an early onset of MG without
      thymoma were carriers of the TNFA*T2 and TNFB*1 alleles. Patients without thymoma
      who had the titin antibody had the same high frequency of TNFA*T1 and TNFB*2 as
      patients with thymoma, whereas patients without the titin antibody carried the
      same allele, TNFA*T2 and TNFB*1, regardless of age and thymic disease. No
      association was found with acetylcholine-receptor levels or disease severity for
      any of the TNFA or TNFB polymorphisms. CONCLUSION: Patients having MG, including
      those with thymoma, who have the titin antibody are most often homozygous for the
      TNFA*T1 and TNFB*2 alleles, whereas the presence of the TNFA*T2 and TNFB*1
      alleles correlates with early-onset MG and the absence of titin antibodies.

PMID- 10199336
TI  - Prolonged sympathetic reflex latency on skin nerves in sporadic cerebellar
      degeneration.
AB  - BACKGROUND: Many physiological or pharmacological evaluations of autonomic
      function have been performed in patients with various types of cerebellar
      degeneration (CD). Few studies have been done, however, using neurographic
      recordings in patients with CD, especially of sudomotor or vasoconstrictor
      nerves. OBJECTIVE: To confirm the clinical importance of sympathetic reflex
      latencies on the skin nerves of patients with various types of CD. DESIGN AND
      SETTING: Case-comparison study at an academic center. PARTICIPANTS: We studied 12
      patients who had sporadic CD (cerebellar cortical atrophy, olivopontocerebellar
      atrophy, and Shy-Drager syndrome) and 15 healthy volunteers as controls. METHODS:
      Skin sympathetic nerve activity (SSNA), sympathetic skin response, and skin
      vasomotor reflex were simultaneously recorded using randomly administered
      electrical stimuli. RESULTS: In controls, SSNA reflex latency ranged from 640 to
      864 milliseconds. Patients with cerebellar cortical atrophy exhibited slight but
      significant (P<.01) prolongation of reflex latency to the onset of reflex bursts.
      In patients with olivopontocerebellar atrophy, latency to the onset and the peak
      of reflex bursts was significantly prolonged (P<.001). Patients with Shy-Drager
      syndrome had no SSNA, sympathetic skin response, or skin vasomotor reflex, even
      with supramaximal electrical stimuli. CONCLUSIONS: Prolonged reflex latency or
      the absence of reflex bursts on SSNA can be observed in patients with CD with
      various forms of autonomic dysfunction. The measurement of SSNA reflex latency
      may be a useful method of evaluating sympathetic function, including the central
      pathway.

PMID- 10199337
TI  - Region-specific corpus callosum atrophy correlates with the regional pattern of
      cortical glucose metabolism in Alzheimer disease.
AB  - BACKGROUND: Positron emission tomographic studies of patients with Alzheimer
      disease (AD) suggest a loss of metabolic functional interactions between
      different cortical regions. Atrophy of the corpus callosum as the major tract of
      intracortical connective fibers may reflect decreased cortical functional
      integration in AD. OBJECTIVES: To investigate whether regional atrophy of the
      corpus callosum is correlated with regional reductions of cortical glucose
      metabolism, as shown by positron emission tomography, and whether primary white
      matter degeneration is a possible cofactor of corpus callosum atrophy in AD.
      PATIENTS AND METHODS: We measured total and regional cross-sectional areas of the
      corpus callosum on midsagittal magnetic resonance imaging scans from 12 patients
      with AD and 15 age-matched control subjects. Regional cerebral metabolic rates
      for glucose in cortical lobes were measured by positron emission tomography using
      fludeoxyglucose F 18. White matter hyperintensities were rated in T2-weighted
      magnetic resonance imaging scans. RESULTS: The total cross-sectional area of
      corpus callosum was significantly reduced in patients with AD, with the most
      prominent changes in the rostrum and splenium and relative sparing of the body of
      the corpus callosum. Frontal and parietal lobe metabolism was correlated with the
      truncal area of the corpus callosum in AD. The ratios of frontal to parietal and
      of frontal to occipital metabolism were correlated with the ratio of anterior to
      posterior corpus callosum area in the group with AD. White matter
      hyperintensities did not correlate with corpus callosum atrophy in the patients
      with AD. CONCLUSION: The regional pattern of corpus callosum atrophy correlated
      with reduced regional glucose metabolism independently of primary white matter
      degeneration in the patients with AD.

PMID- 10199338
TI  - A randomized placebo-controlled comparative trial of gabapentin and propranolol
      in essential tremor.
AB  - BACKGROUND: New medication is needed to treat essential tremor. Preliminary
      evidence suggests that gabapentin may be effective in the treatment of this
      disorder. OBJECTIVE: To study the effects of gabapentin in a comparative, double
      blind, crossover, placebo-controlled trial of patients who have essential tremor.
      PATIENTS AND METHODS: 16 patients with essential tremor (6 with a new onset and
      10 with a 2-week washout period of previous treatment with propranolol
      hydrochloride) received gabapentin (Neurontin), 400 mg 3 times daily; propranolol
      hydrochloride, 40 mg 3 times daily; and placebo for 15 days with a 1-week washout
      period between treatments. MAJOR OUTCOME MEASURES: Major outcome evaluations
      consisted of a Tremor Clinical Rating Scale, accelerometric recordings, and a
      self-reported disability scale obtained before drug intake on study days 1 and 15
      of each treatment period. In addition, the initial (day 1) and superimposed (day
      15) drug effects were studied before and 2, 4, 6, and 8 hours after drug intake.
      RESULTS: At day 15, both gabapentin and propranolol demonstrated significant and
      comparable efficacy in reducing tremor from baseline in all tremor measures. The
      initial drug effects evaluated through accelerometry revealed no significant
      changes with the use of a placebo, but gabapentin and propranolol use
      significantly reduced tremor power. CONCLUSION: Gabapentin may be useful for the
      treatment of essential tremor.

PMID- 10199339
TI  - Successful use of alternate waste nitrogen agents and hemodialysis in a patient
      with hyperammonemic coma after heart-lung transplantation.
AB  - BACKGROUND: Lethal hyperammonemic coma has been reported in 2 adults after lung
      transplantation. It was associated with a massive elevation of brain glutamine
      levels, while plasma glutamine levels were normal or only slightly elevated. In
      liver tissue, glutamine synthetase activity was markedly reduced, and the
      histologic findings resembled those of Reye syndrome. The adequacy of therapy
      commonly used for inherited disorders of the urea cycle has not been adequately
      evaluated in patients with this form of secondary hyperammonemia. OBJECTIVE: To
      determine whether hemodialysis, in conjunction with intravenous sodium
      phenylacetate, sodium benzoate, and arginine hydrochloride therapy, would be
      efficacious in a patient with hyperammonemic coma after solid-organ
      transplantation. DESIGN: Case report. SETTING: A children's hospital. PATIENT: A
      41-year-old woman with congenital heart disease developed a hyperammonemic coma
      with brain edema 19 days after undergoing a combined heart and lung
      transplantation. METHODS: Ammonium was measured in plasma. Amino acids were
      quantitated in plasma and cerebrospinal fluid by column chromatography. The
      effectiveness of therapy was assessed by measuring plasma ammonium levels and
      intracranial pressure and performing sequential neurological examinations.
      RESULTS: The patient had the anomalous combination of increased cerebrospinal
      fluid and decreased plasma glutamine levels. To our knowledge, she is the first
      patient with this complication after solid-organ transplantation to survive after
      combined therapy with sodium phenylacetate, sodium benzoate, arginine
      hydrochloride, and hemodialysis. Complications of the acute coma included focal
      motor seizures, which were controlled with carbamazepine, and difficulty with
      short-term memory. CONCLUSIONS: The aggressive use of hemodialysis in conjunction
      with intravenous sodium phenylacetate, sodium benzoate, and arginine
      hydrochloride therapy may allow survival in patients after solid-organ
      transplantation. An acute acquired derangement in extra-central nervous system
      glutamine metabolism may play a role in the production of hyperammonemia in this
      illness that resembles Reye syndrome, and, as in other hyperammonemic disorders,
      the duration and degree of elevation of brain glutamine levels may be the
      important determining factors in responsiveness to therapy.

PMID- 10199340
TI  - Images in neurology. The cutaneous stigmata of Fabry disease: an X-linked
      phakomatosis associated with central and peripheral nervous system dysfunction.

PMID- 10199341
TI  - Neurology was there--1960.

PMID- 10199342
TI  - State funding and data disclosure.

PMID- 10199343
TI  - NICE: a step forward in the quality of NHS care. National Institute for Clinical
      Excellence. National Health Service.

PMID- 10199344
TI  - Are there good and bad carbohydrates for HDL cholesterol?

PMID- 10199345
TI  - Elective caesarean section for prevention of vertical transmission of HIV-1
      infection.

PMID- 10199346
TI  - More (or less) on Broca.

PMID- 10199347
TI  - A pill a day, or two, for hepatitis B?

PMID- 10199348
TI  - Are clinical trials of therapeutic agents for MS long enough?

PMID- 10199350
TI  - Spinal-cord stimulation in critical limb ischaemia: a randomised trial. ESES
      Study Group.
AB  - BACKGROUND: For patients with critical limb ischaemia, spinal-cord stimulation
      has been advocated for the treatment of ischaemic pain and the prevention of
      amputation. We compared the efficacy of the addition of spinal-cord stimulation
      to best medical treatment in a randomised controlled trial. METHODS: 120 patients
      with critical limb ischaemia not suitable for vascular reconstruction were
      randomly assigned either spinal-cord stimulation in addition to best medical
      treatment or best medical treatment alone. Primary outcomes were mortality and
      amputation. The primary endpoint was limb survival at 2 years. FINDINGS: The mean
      (SD) age of the patients was 72.6 years (10.3). Median (IQR) follow-up was 605
      days (244-1171). 40 (67%) of 60 patients in the spinal-cord-stimulator group and
      41 (68%) of 60 patients in the standard group were alive at the end of the study,
      (p=0.96). There were 25 major amputations in the spinal-cord-stimulator group and
      29 in the standard group, (p=0.47). The hazard ratio for survival at 2 years
      without major amputation in the spinal-cord stimulation group compared with the
      standard group was 0.96 (95% CI 0.61-1.51). INTERPRETATION: Spinal-cord
      stimulation in addition to best medical care does not prevent amputation in
      patients with critical limb ischaemia.

PMID- 10199351
TI  - Glycaemic index as a determinant of serum HDL-cholesterol concentration.
AB  - BACKGROUND: Diet influences the prevalence of coronary heart disease (CHD).
      Insulin sensitivity and concentrations of HDL cholesterol, two metabolic
      predictors of CHD, are also influenced by diet. Dietary carbohydrates with a high
      glycaemic index cause a high postprandial glucose and insulin response, and are
      associated with decreased insulin sensitivity and an increased risk of CHD. This
      study examined whether the glycaemic index of dietary carbohydrates is a
      determinant of serum HDL-cholesterol concentrations. METHOD: Dietary,
      anthropometric, and biochemical data from the 1986-87 Survey of British Adults
      (n=2200) were reanalysed by a multiple regression model, which examined the
      relation between serum total cholesterol, HDL-cholesterol, and calculated LDL
      cholesterol concentrations and various dietary characteristics, including the
      type of carbohydrate, the glycaemic index, and fat intake. FINDINGS: Among the
      1420 participants with complete data, there was a significant negative relation
      between serum HDL-cholesterol concentration and the glycaemic index of the diet
      for both men (regression coefficient -0.00724 [95% CI -0.0101 to -0.00434],
      p=0.02) and women (-0.01326 [-0.0162 to -0.0102], p<0.0001). No other significant
      relation was found with total cholesterol or LDL-cholesterol concentration or
      with any other dietary carbohydrate or fat constituent. INTERPRETATION: In a
      cross-sectional study of middle-aged adults, the glycaemic index of the diet was
      the only dietary variable significantly related to serum HDL-cholesterol
      concentration. Thus, the glycaemic index of the diet is a stronger predictor than
      dietary fat intake of serum HDL-cholesterol concentration.

PMID- 10199352
TI  - Association of variants of the gene for mannose-binding lectin with
      susceptibility to meningococcal disease. Meningococcal Research Group.
AB  - BACKGROUND: The reasons why meningococcal disease develops in only a small
      proportion of individuals carrying the causative bacteria are unknown.
      Differences in host responses to bacterial colonisation are thought to be
      involved, since people with deficiencies in the terminal components of the
      complement pathway, or of properdin, are susceptible to meningococcal disease. We
      postulate that genetic variants of mannose-binding lectin (MBL), a plasma opsonin
      that initiates another pathway of complement activation, might similarly cause
      susceptibility to meningococcal disease. METHODS: The frequency of variants of
      the MBL gene was ascertained in children with meningococcal disease and controls
      from two independent studies; one hospital-based (194 patients and 272 controls
      [patients with non-infectious disorders]), and one community-based (72 patients
      and 110 controls [healthy individuals]), by means of PCR and restriction-enzyme
      digestion, with confirmation by DNA sequencing. FINDINGS: The proportion of
      people homozygous for MBL-variant alleles was higher in patients with
      meningococcal disease than in controls in the hospital study (15 [7.7%] vs four
      [1.5%]; odds ratio 6.5 [95% CI 2.0-27.2]) and in the community study (six [8.3%]
      vs three [2.7%]; 4.5 [0.9-29.1]). The population attributable fraction of cases
      attributable to MBL variants (homozygous and heterozygous) was 32%.
      INTERPRETATION: The MBL pathway is a critical determinant of meningococcal
      disease susceptibility, and genetic variants of MBL might account for a third of
      all disease cases.

PMID- 10199349
TI  - Elective caesarean-section versus vaginal delivery in prevention of vertical HIV
      1 transmission: a randomised clinical trial.
AB  - BACKGROUND: Results from observational studies suggest that caesarean-section
      delivery may reduce the risk of mother-to-child transmission of HIV-1 infection
      in comparison with vaginal delivery. We carried out a randomised clinical trial
      to address this issue and to assess the extent of postdelivery complications.
      METHODS: Eligible women were between 34 and 36 weeks of pregnancy, with a
      confirmed diagnosis of HIV-1 infection, and without an indication for caesarean
      section delivery or a contraindication to this mode of delivery. Women were
      randomly assigned elective caesarean-section delivery at 38 weeks of pregnancy or
      vaginal delivery. An infant was classified as uninfected if he or she became
      negative for antibody to HIV-1 by age 18 months or was negative for virus by PCR
      or culture on at least two occasions, with no clinical, immunological, or viral
      evidence of infection. From 1993, to March, 1998, 436 women were randomised.
      FINDINGS: We present the results of an analysis updated to November, 1998, with
      data on the infection status of 370 infants. Three (1.8%) of 170 infants born to
      women assigned caesarean-section delivery were infected, compared with 21 (10.5%)
      of 200 born to women assigned vaginal delivery (p<0.001). Seven (3.4%) of 203
      infants of women who actually gave birth by caesarean section were infected
      compared with 15 (10.2%) of 167 born vaginally (p=0.009). There were few
      postpartum complications and no serious adverse events in either group.
      INTERPRETATION: Our findings provide evidence that elective caesarean-section
      delivery significantly lowers the risk of mother-to-child transmission of HIV-1
      infection without a significantly increased risk of complications for the mother.

PMID- 10199353
TI  - Prevalence and detection of serious psychiatric disorder in defendants attending
      court.
AB  - BACKGROUND: Diversion programmes in magistrates' courts are designed to provide
      immediate advice or access to mental-health treatment facilities for defendants
      when appropriate. The prevalence of serious psychiatric disorder and the
      proportion of defendants who might require transfer are unknown. We undertook a
      study to address these issues and to find out whether defendants with such
      disorders are reliably detected by court personnel and referred to psychiatric
      staff in court diversion programmes. METHODS: A two-phase screening method used
      questionnaires for psychiatric disorder (the general health questionnaire and
      psychotic screening questionnaire) and screening instruments for alcohol and
      substance misuse followed by standard psychiatric interview (schedules for
      clinical assessment in neuropsychiatry). The detection rate of defendants with
      serious psychiatric disorder by court staff was observed. FINDINGS: The frequency
      of serious psychiatric disorder was 1.31% (three of 229) among defendants
      appearing in court direct from the community and 6.57% (96 of 1460) among those
      held in custody overnight. Of the 99 defendants with serious psychiatric
      disorder, 34 had schizophrenia and other psychoses and 55 had depressive
      disorders. 42 (76%) of the 55 individuals with depressive disorders had suicidal
      ideas, which were recorded on the first-phase screening questionnaire in many
      cases. Only 14 of 96 defendants from overnight custody with serious psychiatric
      disorder were detected by court staff and referred to the court diversion
      programme. INTERPRETATION: There is a substantial rate of psychiatric disorder in
      the court population, which is not satisfactorily detected with the current
      system. Brief screening questionnaires and training of court staff are probably
      necessary for detection of people with serious psychiatric disorder passing
      through the courts.

PMID- 10199355
TI  - Muscle pain after exercise.

PMID- 10199354
TI  - Brain regions involved in articulation.
AB  - BACKGROUND: The left inferior frontal gyrus (Broca's area) is generally believed
      to be critical for the motor act of speech. A lesion-based analysis has, however,
      shown that the left anterior insula is necessary for accurate articulation. We
      used functional imaging in normal people to show the neural systems involved in
      speech during different speech tasks. METHODS: 12 normal people underwent
      positron emission tomography with oxygen-15-labelled water as tracer. We measured
      cerebral activity while participants performed three different tasks: repetition
      of heard nouns at different rates; listening to single nouns at different rates;
      and anticipation of listening or repetition. We analysed the data with imaging
      software. FINDINGS: Repetition of single words did not activate Broca's area but
      activity in three left-lateralised regions was seen: the anterior insula, a
      localised region in the lateral premotor cortex, and the posterior pallidum. The
      left anterior insula and lateral premotor cortex showed a conjunction of activity
      for hearing and articulation. In addition, articulation modulated the response to
      hearing words in the left dorsolateral temporal cortex, the physiological
      expression of the speaker's auditory attention being directed towards the stimuli
      and not his or her articulated responses. INTERPRETATION: The formulation of an
      articulatory plan is a function of the left anterior insula and lateral premotor
      cortex and not of Broca's area. The left basal ganglia seem to be dominant for
      speech, although the axial muscles involved receive their motor output from both
      cerebral hemispheres.

PMID- 10199356
TI  - Brain proton spectroscopy in dementia: an aid to clinical diagnosis.

PMID- 10199357
TI  - Cholinergic therapy for Down's syndrome.

PMID- 10199358
TI  - An independent pilot study into the accuracy and reliability of home blood
      glucose monitors.

PMID- 10199359
TI  - Hepatocellular adenomas in patients taking danazol for hereditary angio-oedema.

PMID- 10199360
TI  - Wine ethanol, platelets, and Mediterranean diet.

PMID- 10199361
TI  - Validating aminoterminal BNP assays: a word of caution.

PMID- 10199363
TI  - Jhum-jhum: neuropsychiatric symptoms in a Nepali village.

PMID- 10199362
TI  - A new formula for estimating mean aortic pressure.

PMID- 10199364
TI  - Centenarians point the way to healthy ageing.

PMID- 10199365
TI  - Medicare reform hangs in the balance.

PMID- 10199366
TI  - In pursuit of quality: the National Institute for Clinical Excellence.
AB  - In the UK, as elsewhere in the world, there is abundant evidence of unacceptable
      inequalities and inefficiencies in health care. These failures are manifest in
      various ways including inappropriate variations in the uptake and use of health
      technologies of proven value, the too frequent failure to provide patients with
      optimum care for the treatment of common diseases, and the too ready adoption of
      health technologies with no established clinical benefits. Healthcare systems
      worldwide are therefore struggling to find ways to ensure that their health
      professionals are able to provide patients with the highest possible (and
      affordable) standards of clinical care. The British government has committed
      itself to a programme of enhancing the quality of care given to National Health
      Service (NHS) patients. The new National Institute for Clinical Excellence (NICE)
      has been charge with providing NHS staff with clear and robust advice that will
      help them meet their own, and their patients', aspirations. The Institute's
      guidance will cover individual technologies as well as the management of a wide
      range of conditions. NICE will also advise on appropriate methods of clinical
      audit in those areas where it has provided guidance.

PMID- 10199367
TI  - Immunosuppressive strategies in transplantation.

PMID- 10199368
TI  - Fibromyalgia falls foul of a fallacy.

PMID- 10199369
TI  - Coronary risk assessment methods and cholesterol lowering.

PMID- 10199370
TI  - Coronary risk assessment methods and cholesterol lowering.

PMID- 10199372
TI  - Coronary risk assessment methods and cholesterol lowering.

PMID- 10199371
TI  - Coronary risk assessment methods and cholesterol lowering.

PMID- 10199373
TI  - Coronary risk assessment methods and cholesterol lowering.

PMID- 10199374
TI  - Coronary risk assessment methods and cholesterol lowering.

PMID- 10199375
TI  - Seven deaths in Darwin.

PMID- 10199376
TI  - Abnormal retinal vascularisation in preterm children.

PMID- 10199377
TI  - Iron-deficiency anaemia in premenopausal women.

PMID- 10199378
TI  - Is there an inapparent dengue explosion?

PMID- 10199379
TI  - Methadone and quality of life.

PMID- 10199380
TI  - Endotoxaemia, hyperfibrinolysis, and bleeding in cirrhosis.

PMID- 10199381
TI  - Churg-Strauss syndrome and antiasthma therapy.

PMID- 10199382
TI  - Human cloning.

PMID- 10199383
TI  - Human cloning.

PMID- 10199384
TI  - The sacking of JAMA.

PMID- 10199385
TI  - The sacking of JAMA.

PMID- 10199386
TI  - Affirmative action needed in The Lancet.

PMID- 10199387
TI  - The Nobel Chronicles. 1947: Carl Ferdinand Cori (1896-1984); Gerty Theresa
      Radnitz Cori (1896-1957); and Bernardo Alberto Houssay (1887-1971).

PMID- 10199388
TI  - Sketches from The Lancet. Doctors' handwriting.

PMID- 10199389
TI  - Structural characterization of viral neutralizing monoclonal antibodies to
      hepatitis B surface antigen.
AB  - In this study we describe the viral neutralizing activity of murine monoclonal
      antibodies (MAb) specific for hepatitis B surface antigen (HBsAg). This viral
      neutralizing activity was assessed in vitro by employing Hepatitis Delta Virus
      (HDV) and human hepatocytes as target cells. To further characterize these viral
      neutralizing antibodies we generated a panel of anti-idiotypic (anti-Id) reagents
      and serologically characterized these antibodies for epitope specificity, Id
      specificity, and Id heterogeneity. Direct binding and competitive inhibition
      solid phase enzyme immunoassay have demonstrated that two murine MAb specific for
      HBsAg (anti-HBs), designated A1.2 and A3.1, recognize similar or overlapping
      epitopes on HBsAg, while monoclonal anti-HBs, designated A2.1 recognizes a unique
      HBsAg epitope. Further, Id analysis using monoclonal and polyclonal anti-Id
      reagents have identified both a private and a cross-reactive Id, respectively, on
      the anti-HBs, A1.2 preparation. The source of the idiotypic cross-reactivity
      between A1.2 and A3.1 has been identified, using Western blot analysis, to
      conformational determinants expressed by the heavy (H) and light (L) chains of
      these monoclonal anti-HBs. Lastly, the intrastrain antibody repertoire induced
      following HBsAg immunization was found to be relatively restricted in
      heterogeneity by clonotype analysis using isoelectric focusing and affinity
      immunoblot analysis. Interspecies variability in the anti-HBs response was
      observed based on epitope recognition using purified anti-HBs from a variety of
      species.

PMID- 10199390
TI  - The binding of anti-DNA antibodies to phosphorothioate oligonucleotides in a
      solid phase immunoassay.
AB  - Phosphorothioate oligonucleotides (S-oligos) are nucleic acid derivatives that
      are commonly used as antisense agents. These compounds, similar to bacterial DNA
      and CpG oligonucleotides, display a variety of immunological activities in vitro
      and in vivo. To assess further these activities, the antigenicity of a series of
      S-oligos was assessed in the solid phase using anti-DNA antibodies from sera of
      patients with systemic lupus erythematosus. By ELISA, S-oligos bound well to anti
      DNA antibodies under the same conditions as calf thymus DNA antigen. The
      specificity for anti-DNA was established by competition assays showing cross
      inhibition of binding by DNA and S-oligos. Reactivity with anti-DNA was observed
      with S-oligos varying in sequence, suggesting interaction with a conserved
      determinant not strictly dependent on the bases. Furthermore. in comparison with
      a phosphodiester oligomer of the same sequence, a phosphorothioate showed
      dramatically increased activity. These findings indicate that structural features
      associated with the S-oligo backbone promote specific binding to anti-DNA
      antibodies and influence the size requirement for antigenicity in the solid
      phase. These observations thus extend the immunological properties of S-oligos
      and suggest uses of these compounds in the diagnosis and treatment of autoimmune
      disease.

PMID- 10199391
TI  - HIV Tat represses transcription of the beta 2-microglobulin promoter.
AB  - The MHC class I complex, which binds and presents peptide antigen, is composed of
      a class I heavy chain and the beta2-microglobulin light chain. HIV-1, which
      induces a profound immunodeficiency in infected individuals, encodes proteins
      that cause decreased expression of class I heavy chain. We now report that the
      HIV Tat protein, which is a potent transactivator of viral transcription, is also
      a potent repressor of the beta2-microglobulin gene. Repression is mediated
      through the basal promoter of the beta2-microglobulin gene, which is shown to be
      predominantly regulated by an initiator element. Tat repression is further
      augmented by the short viral transcript, TAR, which interacts with Tat. Tat
      mediated repression of beta2-microglobulin expression, together with its known
      repression of class I gene transcription, provides an effective mechanism by
      which HIV could prevent cell surface expression of the MHC class I complex and
      avoid immune surveillance.

PMID- 10199392
TI  - Anti-idiotypic antibody D12 and superantigen SPA both interact with human VH3
      encoded antibodies on the external face of the heavy chain involving FR1, CDR2
      and FR3.
AB  - The mouse monoclonal antibody (mAb) D12 specifically binds in the variable region
      (idiotype) of human V(H)3 encoded antibodies. We used mutational analysis to
      determine the subregions of a V(H)3 encoded antibody which effect the interaction
      with mAb D12. Recombinant antibodies composed of mutant heavy chains were
      produced using the baculovirus expression system. The results of this
      topographical study indicate that the combined conformations of FRI, CDR2 and FR3
      are critical for mAb D12 binding. MAb D12 binding was not effected either by the
      heavy chain CDR3 sequence nor by the light chain. We previously demonstrated that
      structures within the same three subregions are required for the B cell
      superantigen Staphylococcal protein A (SPA) binding to V(H)3 encoded antibodies.
      Thus, some anti-idiotypic antibodies can interact with antibodies in a similar
      fashion to superantigens.

PMID- 10199393
TI  - A single gene for human TRAF-3 at chromosome 14q32.3 encodes a variety of mRNA
      species by alternative polyadenylation, mRNA splicing and transcription
      initiation.
AB  - Human TRAF-3 is a signaling molecule that interacts with the cytoplasmic tails of
      CD40 and other TNF-receptor family members. TRAF-3 mRNA is expressed as two major
      classes of approximately 2 and 8 kb and a number of TRAF-3 encoding cDNA clones
      differ in discrete gene segments. Because this variety of mRNA species could
      result from mRNA processing events and/or multiple genes, the structure and
      localization of TRAF-3 encoding gene elements were determined. FISH and radiation
      hybrid mapping demonstrated that TRAF-3 is located at chromosome 14q32.3,
      approximately 1 Mb centromeric to the Ig heavy chain gene complex. Physical
      mapping of four overlapping genomic PAC clones established that TRAF-3
      transcripts are encoded by a single gene, comprised of 13 exons and spanning 130
      kb. Alternative polyadenylation in the mRNA segment encoded by exon 12 accounts
      for the difference between the 2 kb and the 8 kb classes of transcripts.
      Alternative mRNA splicing in the coding region (encoded by exons 3-12) generates
      transcripts which delete exons 8 (75 nt), 7+8 (156 nt) or 8+9 (168 nt) and that
      encode distinct protein isoforms (delta25, delta52 and delta56 aa, respectively).
      Alternative splicing of exon 2 (139 nt) and alternative transcriptional
      initiation result in mRNA species with distinct 5'UTRs. Together, these data
      indicate that a single TRAF-3 gene encodes a variety of mRNA species by a
      combination of alternative polyadenylation, alternative mRNA splicing and/or
      alternative initiation.

PMID- 10199394
TI  - The structural basis for DNA binding by an anti-DNA autoantibody.
AB  - We have used single and multiple site-directed mutagenesis, and molecular
      modeling, to identify critical residues in the DNA binding site of MAb 2C10, an
      IgG anti-dsDNA autoantibody from an MRL/lpr lupus mouse. Simultaneous replacement
      of four Arg residues in the CDR3H abolished binding activity. With one exception,
      replacement of any one of these Arg residues reduced the activity to 20-50% of
      the unmutated scFv activity. Arg to Asp replacements had a slightly greater
      effect than Arg to Ala replacements. In the one exceptional case, replacement of
      Arg99 with Ala actually increased DNA binding five-fold and replacement by Asp
      had little effect. Mutation of Phe32 and Asn35 to A1a in CDRIH decreased DNA
      binding, whereas replacement of Arg31 with A1a had negligible effect. Ala
      substitution of any one of a cluster of Asp residues in CDR1L increased DNA
      binding three to six-fold, confirming previous findings that the L-chain of MAb
      2C10 is not favorable for DNA binding. The L-chain does participate in shaping
      the selectivity of antigen binding, and mutation of CDR3L residue Asp92 or Asn93
      caused a decrease in DNA binding activity. Directed mutagenesis, consistent with
      a molecular model, indicates that: several CDR amino acids contribute to DNA
      binding, without one residue dominating; both VH and VL CDR3 domains contribute
      to specificity of binding whereas the CDR1L hinders DNA binding. The results
      suggest a significant role for electrostatics in the interaction of DNA with MAb
      2C10.

PMID- 10199395
TI  - Slit branches out: a secreted protein mediates both attractive and repulsive axon
      guidance.

PMID- 10199396
TI  - Increasing the complexity of coactivation in nuclear receptor signaling.

PMID- 10199397
TI  - Deconstructing type 2 diabetes.

PMID- 10199398
TI  - Negative feedback mechanisms and their roles during pattern formation.

PMID- 10199399
TI  - A steroid receptor coactivator, SRA, functions as an RNA and is present in an SRC
      1 complex.
AB  - Nuclear receptors play critical roles in the regulation of eukaryotic gene
      expression. We report the isolation and functional characterization of a novel
      transcriptional coactivator, termed steroid receptor RNA activator (SRA). SRA is
      selective for steroid hormone receptors and mediates transactivation via their
      amino-terminal activation function. We provide functional and mechanistic
      evidence that SRA acts as an RNA transcript; transfected SRA, unlike other
      steroid receptor coregulators, functions in the presence of cycloheximide, and
      SRA mutants containing multiple translational stop signals retain their ability
      to activate steroid receptor-dependent gene expression. Biochemical fractionation
      shows that SRA exists in distinct ribonucleoprotein complexes, one of which
      contains the nuclear receptor coactivator steroid receptor coactivator 1. We
      suggest that SRA may act to confer functional specificity upon multiprotein
      complexes recruited by liganded receptors during transcriptional activation.

PMID- 10199400
TI  - A Smad transcriptional corepressor.
AB  - Following TGFbeta receptor-mediated phosphorylation and association with Smad4,
      Smad2 moves into the nucleus, binds to target promoters in association with DNA
      binding cofactors, and recruits coactivators such as p300/CBP to activate
      transcription. We identified the homeodomain protein TGIF as a Smad2-binding
      protein and a repressor of transcription. A TGFbeta-activated Smad complex can
      recruit TGIF and histone deacetylases (HDACs) to a Smad target promoter,
      repressing transcription. Thus, upon entering the nucleus, a Smad2-Smad4 complex
      may interact with coactivators, forming a transcriptional activation complex, or
      with TGIF and HDACs, forming a transcriptional repressor complex. Formation of
      one of these two mutually exclusive complexes is determined by the relative
      levels of Smad corepressors and coactivators within the cell.

PMID- 10199401
TI  - NELF, a multisubunit complex containing RD, cooperates with DSIF to repress RNA
      polymerase II elongation.
AB  - DRB is a classic inhibitor of transcription elongation by RNA polymerase II (pol
      II). Since DRB generally affects class II genes, factors involved in this process
      must play fundamental roles in pol II elongation. Recently, two elongation
      factors essential for DRB action were identified, namely DSIF and P-TEFb. Here we
      describe the identification and purification from HeLa nuclear extract of a third
      protein factor required for DRB-sensitive transcription. This factor, termed
      negative elongation factor (NELF), cooperates with DSIF and strongly represses
      pol II elongation. This repression is reversed by P-TEFb-dependent
      phosphorylation of the pol II C-terminal domain. NELF is composed of five
      polypeptides, the smallest of which is identical to RD, a putative RNA-binding
      protein of unknown function. This study reveals a molecular mechanism for DRB
      action and a regulatory network of positive and negative elongation factors.

PMID- 10199402
TI  - Active transcriptional repression by the Rb-E2F complex mediates G1 arrest
      triggered by p16INK4a, TGFbeta, and contact inhibition.
AB  - Rb inhibits progression from G1 to S phase of the cell cycle. It associates with
      a number of cellular proteins; however, the nature of these interactions and
      their relative significance in cell cycle regulation are still unclear. We
      present evidence that Rb must normally interact with the E2F family of
      transcription factors to arrest cells in G1, and that this arrest results from
      active transcriptional repression by the Rb-E2F complex, not from inactivation of
      E2F. Thus, a major role of E2F in cell cycle regulation is assembly of this
      repressor complex. We demonstrate that active repression by Rb-E2F mediates the
      G1 arrest triggered by TGFbeta, p16INK4a, and contact inhibition.

PMID- 10199403
TI  - Nef-induced CD4 degradation: a diacidic-based motif in Nef functions as a
      lysosomal targeting signal through the binding of beta-COP in endosomes.
AB  - The Nef protein of primate lentiviruses downregulates the cell surface expression
      of CD4 through a two-step process. First, Nef connects the cytoplasmic tail of
      CD4 with adaptor protein complexes (AP), thereby inducing the formation of CD4
      specific clathrin-coated pits that rapidly endocytose the viral receptor. Second,
      Nef targets internalized CD4 molecules for degradation. Here we show that Nef
      accomplishes this second task by acting as a connector between CD4 and the beta
      subunit of COPI coatomers in endosomes. A sequence encompassing a critical acidic
      dipeptide, located nearby but distinct from the AP-binding determinant of HIV-1
      Nef, is responsible for beta-COP recruitment and for routing to lysosomes. A
      novel class of endosomal sorting motif, based on acidic residues, is thus
      revealed, and beta-COP is identified as its downstream partner.

PMID- 10199404
TI  - Crystal structures of complexes of PcrA DNA helicase with a DNA substrate
      indicate an inchworm mechanism.
AB  - We have determined two different structures of PcrA DNA helicase complexed with
      the same single strand tailed DNA duplex, providing snapshots of different steps
      on the catalytic pathway. One of the structures is of a complex with a
      nonhydrolyzable analog of ATP and is thus a "substrate" complex. The other
      structure contains a bound sulphate ion that sits in a position equivalent to
      that occupied by the phosphate ion produced after ATP hydrolysis, thereby
      mimicking a "product" complex. In both complexes, the protein is monomeric. Large
      and distinct conformational changes occur on binding DNA and the nucleotide
      cofactor. Taken together, these structures provide evidence against an "active
      rolling" model for helicase action but are instead consistent with an "inchworm"
      mechanism.

PMID- 10199405
TI  - Transformation of MutL by ATP binding and hydrolysis: a switch in DNA mismatch
      repair.
AB  - The MutL DNA mismatch repair protein has recently been shown to be an ATPase and
      to belong to an emerging ATPase superfamily that includes DNA topoisomerase II
      and Hsp90. We report here the crystal structures of a 40 kDa ATPase fragment of
      E. coli MutL (LN40) complexed with a substrate analog, ADPnP, and with product
      ADP. More than 60 residues that are disordered in the apoprotein structure become
      ordered and contribute to both ADPnP binding and dimerization of LN40. Hydrolysis
      of ATP, signified by subsequent release of the gamma-phosphate, releases two key
      loops and leads to dissociation of the LN40 dimer. Dimerization of the LN40
      region is required for and is the rate-limiting step in ATP hydrolysis by MutL.
      The ATPase activity of MutL is stimulated by DNA and likely acts as a switch to
      coordinate DNA mismatch repair.

PMID- 10199406
TI  - Phosphorylation of histone H3 is required for proper chromosome condensation and
      segregation.
AB  - Phosphorylation of histone H3 at serine 10 occurs during mitosis in diverse
      eukaryotes and correlates closely with mitotic and meiotic chromosome
      condensation. To better understand the function of H3 phosphorylation in vivo, we
      created strains of Tetrahymena in which a mutant H3 gene (S10A) was the only gene
      encoding the major H3 protein. Although both micronuclei and macronuclei contain
      H3 in typical nucleosomal structures, defects in nuclear divisions were
      restricted to mitotically dividing micronuclei; macronuclei, which are amitotic,
      showed no defects. Strains lacking phosphorylated H3 showed abnormal chromosome
      segregation, resulting in extensive chromosome loss during mitosis. During
      meiosis, micronuclei underwent abnormal chromosome condensation and failed to
      faithfully transmit chromosomes. These results demonstrate that H3 serine 10
      phosphorylation is causally linked to chromosome condensation and segregation in
      vivo and is required for proper chromosome dynamics.

PMID- 10199407
TI  - Cell cycle-dependent polar localization of an essential bacterial histidine
      kinase that controls DNA replication and cell division.
AB  - The master CtrA response regulator functions in Caulobacter to repress
      replication initiation in different phases of the cell cycle. Here, we identify
      an essential histidine kinase, CckA, that is responsible for CtrA activation by
      phosphorylation. Although CckA is present throughout the cell cycle, it moves to
      a cell pole in S phase, and upon cell division it disperses. Removal of the
      membrane-spanning region of CckA results in loss of polar localization and cell
      death. We propose that polar CckA functions to activate CtrA just after the
      initiation of DNA replication, thereby preventing premature reinitiations of
      chromosome replication. Thus, dynamic changes in cellular location of critical
      signal proteins provide a novel mechanism for the control of the prokaryote cell
      cycle.

PMID- 10199408
TI  - The EGF-CFC protein one-eyed pinhead is essential for nodal signaling.
AB  - The zebrafish EGF-CFC gene one-eyed pinhead (oep) is required zygotically for the
      formation of the ventral neuroectoderm, endoderm, and prechordal plate. Here we
      report that embryos lacking both maternal and zygotic Oep activity are defective
      in germ layer formation, organizer development, and the positioning of the
      anterior-posterior axis. An identical phenotype is displayed by double mutants
      for the nodal-related genes squint and cyclops. Mutations in oep eliminate the
      response to Squint and Cyclops overexpression but are suppressed by expression of
      Activin and activated forms of the type I receptor ActRIB and Smad2. Expression
      of the murine EGF-CFC gene cripto rescues oep mutants. These results suggest a
      conserved role for EGF-CFC proteins as essential extracellular cofactors for
      Nodal signaling during vertebrate development.

PMID- 10199410
TI  - Will TSEs taint the US blood supply?

PMID- 10199409
TI  - Germline mutations in the extracellular domains of the 55 kDa TNF receptor,
      TNFR1, define a family of dominantly inherited autoinflammatory syndromes.
AB  - Autosomal dominant periodic fever syndromes are characterized by unexplained
      episodes of fever and severe localized inflammation. In seven affected families,
      we found six different missense mutations of the 55 kDa tumor necrosis factor
      receptor (TNFR1), five of which disrupt conserved extracellular disulfide bonds.
      Soluble plasma TNFR1 levels in patients were approximately half normal.
      Leukocytes bearing a C52F mutation showed increased membrane TNFR1 and reduced
      receptor cleavage following stimulation. We propose that the autoinflammatory
      phenotype results from impaired downregulation of membrane TNFR1 and diminished
      shedding of potentially antagonistic soluble receptor. TNFR1-associated periodic
      syndromes (TRAPS) establish an important class of mutations in TNF receptors.
      Detailed analysis of one such mutation suggests impaired cytokine receptor
      clearance as a novel mechanism of disease.

PMID- 10199411
TI  - Diabetes research plan presented to Congress.

PMID- 10199412
TI  - Passion for poetry, compassion for others.

PMID- 10199413
TI  - From the Food and Drug Administration.

PMID- 10199414
TI  - From the Centers for Disease Control and Prevention. Update: influenza activity-
      United States, 1998-99 season.

PMID- 10199415
TI  - From the Centers for Disease Control and Prevention. HIV postexposure prophylaxis
      registry closing.

PMID- 10199416
TI  - From the Centers for Disease Control and Prevention. New population standard for
      age-adjusting death rates.

PMID- 10199417
TI  - Pharmaceutical benefits managers and optimizing prescribing.

PMID- 10199418
TI  - Pharmaceutical benefits managers and optimizing prescribing.

PMID- 10199419
TI  - Antiviral therapies for long-term suppression of genital herpes.

PMID- 10199420
TI  - Antiviral therapies for long-term suppression of genital herpes.

PMID- 10199421
TI  - Putting computer-based evidence in the hands of clinicians.

PMID- 10199422
TI  - Calcium intake and colon cancer biomarkers.

PMID- 10199424
TI  - Promoting patient safety by preventing medical error.

PMID- 10199423
TI  - Method of physician payment and patient trust.

PMID- 10199425
TI  - Tales of the unnatural: correction.

PMID- 10199426
TI  - Improved out-of-hospital cardiac arrest survival through the inexpensive
      optimization of an existing defibrillation program: OPALS study phase II. Ontario
      Prehospital Advanced Life Support.
AB  - CONTEXT: Survival rates for out-of-hospital cardiac arrest are low; published
      survival rates in Ontario are only 2.5%. This study represents phase II of the
      Ontario Prehospital Advanced Life Support (OPALS) study, which is designed to
      systematically evaluate the effectiveness and efficiency of various prehospital
      interventions for patients with cardiac arrest, trauma, and critical illnesses.
      OBJECTIVE: To assess the impact on out-of-hospital cardiac arrest survival of the
      implementation of a rapid defibrillation program in a large multicenter emergency
      medical services (EMS) system with existing basic life support and defibrillation
      (BLS-D) level of care. DESIGN: Controlled clinical trial comparing survival for
      36 months before (phase I) and 12 months after (phase II) system optimization.
      SETTING: Nineteen urban and suburban Ontario communities (populations ranging
      from 16 000 to 750 000 [total, 2.7 million]). PATIENTS: All patients who had out
      of-hospital cardiac arrest in the study communities for whom resuscitation was
      attempted by emergency responders. INTERVENTIONS: Study communities optimized
      their EMS systems to achieve the target response interval from when a call was
      received until a vehicle stopped with a defibrillator of 8 minutes or less for
      90% of cardiac arrest cases. Working both locally and provincially, communities
      implemented multiple measures, including defibrillation by firefighters, base
      paging, tiered response agreements with fire departments, continuous quality
      improvement for response intervals, and province-wide revision and implementation
      of standard dispatch policies. All response times were obtained from a central
      dispatch system. MAIN OUTCOME MEASURE: Survival to hospital discharge. RESULTS:
      The 4690 cardiac arrest patients studied in phase I and the 1641 in phase II were
      similar for all clinical and demographic characteristics, including age, sex,
      witnessed status, rhythm, and receipt of bystander cardiopulmonary resuscitation.
      The proportion of cases meeting the 8-minute response criterion improved (76.7%
      vs 92.5%; P<.001) as did most median response intervals. Overall survival to
      hospital discharge for all rhythm groups combined improved from 3.9% to 5.2 % (P
      = .03). The 33% relative increase in survival represents an additional 21 lives
      saved each year in the study communities (approximately 1 life per 120000
      residents). The charges were estimated to be US $46900 per life saved for
      establishing the rapid defibrillation program and US $2400 per life saved
      annually for maintaining the program. CONCLUSION: An inexpensive, multifaceted
      system optimization approach to rapid defibrillation can lead to significant
      improvements in survival after cardiac arrest in a large BLS-D EMS system.

PMID- 10199427
TI  - Influence of cardiopulmonary resuscitation prior to defibrillation in patients
      with out-of-hospital ventricular fibrillation.
AB  - CONTEXT: Use of automated external defibrillators (AEDs) by first arriving
      emergency medical technicians (EMTs) is advocated to improve the outcome for out
      of-hospital ventricular fibrillation (VF). However, adding AEDs to the emergency
      medical system in Seattle, Wash, did not improve survival. Studies in animals
      have shown improved outcomes when cardiopulmonary resuscitation (CPR) was
      administered prior to an initial shock for VF of several minutes' duration.
      OBJECTIVE: To evaluate the effects of providing 90 seconds of CPR to persons with
      out-of-hospital VF prior to delivery of a shock by first-arriving EMTs. DESIGN:
      Observational, prospectively defined, population-based study with 42 months of
      preintervention analysis (July 1, 1990-December 31, 1993) and 36 months of post
      intervention analysis (January 1, 1994-December 31, 1996). SETTING: Seattle fire
      department-based, 2-tiered emergency medical system. PARTICIPANTS: A total of 639
      patients treated for out-of-hospital VF before the intervention and 478 after the
      intervention. INTERVENTION: Modification of the protocol for use of AEDs,
      emphasizing approximately 90 seconds of CPR prior to delivery of a shock. MAIN
      OUTCOME MEASURES: Survival and neurologic status at hospital discharge determined
      by retrospective chart review as a function of early (<4 minutes) and later (> or
      =4 minutes) response intervals. RESULTS: Survival improved from 24% (155/639) to
      30% (142/478) (P=.04). That benefit was predominantly in patients for whom the
      initial response interval was 4 minutes or longer (survival, 17% [56/321] before
      vs 27% [60/220] after; P = .01). In a multivariate logistic model, adjusting for
      differences in patient and resuscitation factors between the periods, the
      protocol intervention was estimated to improve survival significantly (odds
      ratio, 1.42; 95% confidence interval, 1.07-1.90; P = .02). Overall, the
      proportion of victims who survived with favorable neurologic recovery increased
      from 17% (106/634) to 23% (109/474) (P = .01). Among survivors, the proportion
      having favorable neurologic function at hospital discharge increased from 71%
      (106/150) to 79% (109/138) (P<.11). CONCLUSION: The routine provision of
      approximately 90 seconds of CPR prior to use of AED was associated with increased
      survival when response intervals were 4 minutes or longer.

PMID- 10199428
TI  - Distribution of and factors associated with serum homocysteine levels in
      children: Child and Adolescent Trial for Cardiovascular Health.
AB  - CONTEXT: Although evidence suggests that homocysteine is a risk factor for
      cardiovascular disease in adults, little information exists on homocysteine
      levels in children. OBJECTIVES: To describe the distribution of serum
      homocysteine concentrations among children and to examine the association between
      homocysteine levels and several characteristics, including serum levels of folic
      acid and vitamins B12 and B6. DESIGN: Cross-sectional analysis. SETTING: School
      based cohort from California, Louisiana, Minnesota, and Texas. PARTICIPANTS: A
      total of 3524 US schoolchildren, aged 13 and 14 years, from the Child and
      Adolescent Trial for Cardiovascular Health (completed in 1994). Measurement was
      conducted in 1997. MAIN OUTCOME MEASURE: Nonfasting serum total homocysteine
      concentration. RESULTS: The distribution of homocysteine values ranged from 0.1
      to 25.7 micromol/L (median, 4.9 micromol/L). Geometric mean homocysteine
      concentration was significantly higher in boys (5.22 micromol/L) than girls (4.84
      micromol/L); blacks (5.51 micromol/L) than whites (4.96 micromol/L) or Hispanics
      (4.93 micromol/L); nonusers of multivitamins (5.09 micromol/L) than users (4.82
      micromol/L); and smokers (5.19 micromol/L) than nonsmokers (5.00 micromol/ L).
      Serum homocysteine was significantly inversely correlated with serum levels of
      folic acid (r= -0.36; P = .001), vitamin B12 (r = -0.21; P = .001), and vitamin
      B6 (r = -0.18; P = .001). Serum homocysteine was not significantly associated
      with serum lipid levels or family history of cardiovascular disease and was only
      weakly related to body mass index and systolic blood pressure. After multivariate
      adjustment, homocysteine remained independently associated with sex, race, serum
      folic acid and vitamin B12 levels, and systolic blood pressure. CONCLUSIONS: The
      distribution of homocysteine levels in children is substantially lower than that
      observed for adults; however, a small percentage of children are still
      potentially at elevated risk for future cardiovascular disease. Serum folic acid
      may be an important determinant of homocysteine levels in children.

PMID- 10199429
TI  - Effect of estrogen on brain activation patterns in postmenopausal women during
      working memory tasks.
AB  - CONTEXT: Preclinical studies suggest that estrogen affects neural structure and
      function in mature animals; clinical studies are less conclusive with many, but
      not all, studies showing a positive influence of estrogen on verbal memory in
      postmenopausal women. OBJECTIVE: To investigate the effects of estrogen on brain
      activation patterns in postmenopausal women as they performed verbal and
      nonverbal working memory tasks. DESIGN: Randomized, double-blind, placebo
      controlled, crossover trial from 1996 through 1998. SETTING: Community volunteers
      tested in a hospital setting. PATIENTS: Forty-six postmenopausal women aged 33 to
      61 years (mean [SD] age, 50.8 [4.7] years). INTERVENTION: Twenty-one-day
      treatment with conjugated equine estrogens, 1.25 mg/d, randomly crossed over with
      identical placebo and a 14-day washout between treatments. MAIN OUTCOME MEASURES:
      Brain activation patterns measured using functional magnetic resonance imaging
      during tasks involving verbal and nonverbal working memory. RESULTS: Treatment
      with estrogen increased activation in the inferior parietal lobule during storage
      of verbal material and decreased activation in the inferior parietal lobule
      during storage of nonverbal material. Estrogen also increased activation in the
      right superior frontal gyrus during retrieval tasks, accompanied by greater left
      hemisphere activation during encoding. The latter pattern represents a sharpening
      of the hemisphere encoding/retrieval asymmetry (HERA) effect. Estrogen did not
      affect actual performance of the verbal and nonverbal memory tasks. CONCLUSIONS:
      Estrogen in a therapeutic dosage alters brain activation patterns in
      postmenopausal women in specific brain regions during the performance of the
      sorts of memory function that are called upon frequently during any given day.
      These results suggest that estrogen affects brain organization for memory in
      postmenopausal women.

PMID- 10199430
TI  - Relationship between fasting plasma glucose and glycosylated hemoglobin:
      potential for false-positive diagnoses of type 2 diabetes using new diagnostic
      criteria.
AB  - CONTEXT: New criteria for the diagnosis of type 2 diabetes mellitus have recently
      been introduced that lowered the diagnostic fasting plasma glucose (FPG)
      concentration from 7.8 to 7.0 mmol/L (140 to 126 mg/dL). OBJECTIVE: To determine
      if individuals with diabetes diagnosed by the new FPG concentration criterion
      would have excessive glycosylation (elevated hemoglobin [HbA1c] levels).
      DEFINITIONS: We determined the distribution of HbA1c levels in individuals using
      4 classifications: (1) normal by the new criterion (FPG concentration <6.1 mmol/L
      [110 mg/dL]); (2) impaired fasting glucose by the new criterion (FPG
      concentration of 6.1-6.9 mmol/L [110-125 mg/dL]); (3) diabetes diagnosed solely
      by the new FPG concentration criterion of 7.0 through 7.7 mmol/L (126-139 mg/dL);
      and (4) diabetes diagnosed by the previous FPG concentration criterion of 7.8
      mmol/L (140 mg/dL) or higher. DESIGN: Cross-sectional analysis of 2 large data
      sets (NHANES III and Meta-Analysis Research Group [MRG] on the Diagnosis of
      Diabetes Using Glycated Hemoglobin) that contained individuals in whom FPG
      concentrations, 2-hour glucose concentrations using an oral glucose tolerance
      test, and an HbA1c level were simultaneously measured. We cross-tabulated FPG
      concentrations (<6.1 mmol/L [110 mg/dL], 6.1-6.9 mmol/L [110-125 mg/dL], 7.0-7.7
      mmol/L [126-139 mg/dL], and > or =7.8 mmol/L [140 mg/dL]) and HbA1c levels
      separated into 3 intervals: normal, less than the upper limit of normal (ULN);
      slightly elevated, ULN to ULN plus 1%; and high, higher than ULN plus 1%.
      RESULTS: Among subjects with normal FPG concentrations, HbA1c levels in the
      NHANES III (and the MRG) data sets were normal in 97.3% (96.2%), slightly
      elevated in 2.7% (3.6%), and high in 0.1% (0.2%). Among individuals with impaired
      fasting glucose, HbA1c concentrations were normal in 86.7% (81.4%), slightly
      elevated in 13.1% (16.4%), and high in 0.2% (2.2%). Among diabetic patients
      diagnosed by the new FPG criterion only, HbA1c levels were normal in 60.9%
      (59.6%), slightly elevated in 35.8% (32.8%), and high in 3.4% (7.6%). In diabetic
      patients diagnosed by the former FPG criterion, HbA1c levels were normal in 18.6%
      (16.7%), slightly elevated in 32.5% (21.0%), and high in 48.9% (62.3%).
      CONCLUSIONS: About 60% of the new cohort of diabetic patients in both data sets
      have normal HbA1c levels. We believe that diabetes should not be diagnosed in
      those with FPG concentrations less than 7.8 mmol/L (140 mg/dL) unless excessive
      glycosylation is evident. Individuals without excessive glycosylation but with
      moderate elevations of FPG concentrations (6.1-7.7 mmol/L [110-139 mg/dL]) should
      be diagnosed as having impaired fasting glucose and treated with an appropriate
      diet and exercise. This diagnostic labeling achieves the goal of early
      intervention without subjecting these persons to the potentially negative
      insurance, employment, social, and psychological consequences of a diagnosis of
      diabetes mellitus.

PMID- 10199431
TI  - An international study of patient compliance with hemodialysis.
AB  - CONTEXT: International differences in compliance of patients undergoing
      hemodialysis are poorly characterized and could contribute to international
      survival differences. OBJECTIVE: To compare international differences in patient
      compliance with hemodialysis treatments. DESIGN: A prospective observational
      study of patients undergoing hemodialysis in 1995 and a cross-sectional survey of
      health care professionals caring for hemodialyzed patients in 1996. SETTING AND
      PATIENTS: Four dialysis centers in the southeastern United States with 415
      patients undergoing hemodialysis, 1 center in Sweden with 84 patients, and 4
      centers in Japan with 194 patients participated in the prospective observational
      study. In the cross-sectional survey, nurses and nephrologists from the United
      States (n = 49), Japan (n = 21), and Sweden (n = 16) responded to questions
      regarding the compliance of their patients undergoing hemodialysis. MAIN OUTCOME
      MEASURES: Percentage of patients who miss a dialysis treatment and number of
      missed dialysis treatments. RESULTS: Of 415 US patients, 147 missed 699
      treatments over a 6-month period (28.1 missed treatments per 100 patient-months
      or 2.3% of all prescribed treatments). During a 3-month period, there were 0
      missed treatments per 100 patient-months for patients from Japan and 0 missed
      treatments per 100 patient-months for patients from Sweden (P<.001). In the cross
      sectional survey, the mean (SD) estimated percentage of patients missing a
      treatment per month was 4% (3%) for the United States, 0% for Japan, and 0.1%
      (3%) for Sweden (P<.001). CONCLUSIONS: Noncompliance is much more common in US
      patients undergoing hemodialysis than Swedish and Japanese patients. The
      implications of these results for international differences in survival deserve
      further study.

PMID- 10199432
TI  - Users' guides to the medical literature: XV. How to use an article about disease
      probability for differential diagnosis. Evidence-Based Medicine Working Group.

PMID- 10199433
TI  - Advancing cardiac resuscitation: lessons from externally controlled trials.

PMID- 10199434
TI  - When is diabetes diabetes?

PMID- 10199435
TI  - The new face of medical education.

PMID- 10199436
TI  - Medicare antifraud initiatives: effects on resident education.

PMID- 10199437
TI  - Medicare's role in financing graduate medical education.

PMID- 10199438
TI  - An apology for those who leave medicine.

PMID- 10199440
TI  - JAMA patient page: CPR.

PMID- 10199439
TI  - Historical perspective of medical residency training: 50 years of changes.

PMID- 10199441
TI  - Patterns of treatment for older women with newly diagnosed breast carcinoma.
AB  - The patterns of treatment for newly diagnosed breast carcinomas in older women
      aged 65 years or more have not been well studied, particularly in relation to
      screening mammography performed for the early detection of breast cancer.
      Therefore, the present study was performed to determine the patterns of treatment
      for newly diagnosed breast carcinomas in older women aged 65 years or more and to
      determine the impact of screening mammography on these patterns of treatment. The
      study population consisted of 130 women aged 65 years or more with newly
      diagnosed breast carcinoma from 1993 through 1994 enrolled in a large health
      maintenance organization. The medical records of these 130 patients were
      reviewed. The breast cancers detected in women who had undergone mammographic
      screening were more often eligible for breast-conservation treatment than the
      breast cancers detected in women who had not undergone mammographic screening
      (79% vs. 48%, respectively; p = 0.0044). For the breast cancers that were
      eligible for breast-conservation treatment, breast-conservation treatment was
      used more often for the women who had undergone mammographic screening than for
      the women who had not undergone mammographic screening (70% vs. 27%,
      respectively; p = 0.0077). Definitive radiation therapy was delivered after
      breast-conservation surgery in 89% (55/62) of the patients. Medical oncology
      consultation was obtained more commonly for more advanced staged breast cancers.
      Clinical management was altered in 9% (12/130) of the patients because of older
      patient age, comorbid medical conditions, or both. These findings have documented
      the patterns of treatment for older women aged 65 years or more with newly
      diagnosed breast cancer. Screening mammography had a significant impact on the
      patterns of breast cancer management, as demonstrated by the association of
      screening mammography with an increased eligibility for breast-conservation
      treatment and an increased use of breast-conservation treatment for eligible
      patients.

PMID- 10199442
TI  - Early postoperative complications of splenectomy for hematologic disease.
AB  - Splenectomy may be indicated in a variety of hematologic diseases for diagnostic
      reasons, therapeutic reasons, or both. Most reviews reveal a high proportion of
      procedures performed as part of the staging process for Hodgkin disease.
      Splenectomy for myelofibrosis has been associated with an increased postoperative
      complication rate. Other determinants of morbidity have been splenic weight and
      operative blood loss. The authors reviewed a series of 83 adult patients from a
      prospective database established in 1991 to determine the incidence of early
      postoperative complications associated with splenectomy for hematologic disease
      and to analyze patient characteristics that may predict their occurrence.
      Morbidity that occurred within 30 days of splenectomy was considered to be an
      early postoperative complication. Operative estimated blood loss and incidence of
      postoperative complications were correlated with patient age, preoperative
      platelet count, splenic weight, and diagnosis of myelofibrosis as regression
      covariates. Indications for splenectomy were therapeutic in 76 patients (92%).
      Median splenic weight was 760 g, and 22 patients had massive splenomegaly.
      Patients with splenic weight more than 1,500 g had a significantly higher median
      estimated blood loss (300 ml; p = 0.02). Splenic weight was the main determinant
      of estimated blood loss in a multiple linear regression analysis (p = 0.02).
      Twenty-two patients (27%) experienced postoperative complications and five of
      those patients died (6%). Patients with myelofibrosis had the highest incidence
      of complications (50%) and the highest postoperative mortality (21%; p = 0.04).
      In a logistic regression model, estimated blood loss was the only variable
      significantly correlated with postoperative complications (p = 0.02). Splenectomy
      for hematologic disease is associated with an acceptable early postoperative
      complication rate, even when the indication is predominantly therapeutic.
      Patients at particularly high risk include those with elevated operative blood
      loss, massive splenomegaly, and myelofibrosis.

PMID- 10199443
TI  - Impact of clinical, pathologic, and treatment-related factors on outcome in
      patients with locally advanced breast cancer treated with multimodality therapy.
AB  - The authors reviewed the experience at their institution treating patients with
      locally advanced breast cancer using multimodality therapy to identify clinical,
      pathologic, and treatment-related factors affecting outcome. One hundred patients
      with locally advanced breast cancer were treated with definitive therapy at
      William Beaumont Hospital. Three patients had stage IIB disease, 45 patients had
      stage IIIA disease, and 52 patients had IIIB disease. Thirteen patients had
      inflammatory breast carcinoma. Seventy-four patients (74%) received trimodality
      therapy consisting of systemic therapy, radiation therapy, and surgery. Systemic
      therapy was delivered to 90 patients. Eighty-three patients (83%) received
      adjuvant radiation therapy. Eighty-five patients underwent mastectomy (85%).
      Multiple clinical, pathologic, and treatment-related factors were analyzed for
      their impact on outcome. The median follow-up was 47 months. Overall, the 5-year
      actuarial rates of local control, disease-free survival, overall survival, and
      cause-specific survival were 81%, 43%, 53%, and 55%, respectively. The 5-year
      actuarial cause-specific survival rates for patients with inflammatory breast
      carcinoma, stage IIIA disease, and stage IIIB disease were 25%, 55%, and 53%,
      respectively. On multivariate analysis, local control was improved with radiation
      therapy (p = 0.008) and the absence of inflammatory breast carcinoma (p = 0.008).
      Disease-free survival was improved with the addition of radiation therapy (p =
      0.001) and with less than four positive lymph nodes (p = 0.003). Distant
      metastasis-free survival was improved in patients without inflammatory breast
      carcinoma (p = 0.0249) and with less than four involved lymph nodes (p = 0.0135).
      Cause-specific survival and overall survival were adversely affected by the
      presence of inflammatory breast carcinoma (p = 0.0135 and p = 0.0325,
      respectively) or four or more involved lymph nodes (p = 0.0082 and p = 0.012,
      respectively). Radiation therapy appears to be a critical component in the
      overall treatment of patients with locally advanced breast cancer by improving
      the rates of local control and disease-free survival. Other adverse factors for
      survival include four or more positive lymph nodes and inflammatory breast
      carcinoma.

PMID- 10199444
TI  - Prospective randomized comparison of tropisetron with and without dexamethasone
      against high-dose metoclopramide in prophylaxis of acute and delayed cisplatin
      induced nausea and vomiting.
AB  - Several studies have confirmed the efficacy of high-dose metoclopramide and, more
      recently, serotonin antagonists, with and without dexamethasone, in the
      prophylaxis of cisplatin-induced nausea and vomiting. Most of these trials have
      been reported from Western countries. There is little or no information about the
      efficacy and tolerability of these agents in ethnic groups in other countries.
      Furthermore, many patients in the developing countries cannot afford serotonin
      antagonists. The result is a critical need to evaluate these agents and justify
      their increasingly common use. The authors performed a prospective randomized
      trial to compare the efficacy and tolerability of tropisetron with and without
      dexamethasone against high-dose metoclopramide cocktail in patients receiving a
      uniform dose of cisplatin (100 mg/m2). Metoclopramide 2 mg/kg was combined with
      clemastine, dexamethasone, and lorazepam. These drugs were initially repeated at
      short intervals and subsequently given in the oral form for the next 5 days.
      Tropisetron 5 mg was administered intravenously 15 minutes immediately before
      cisplatin therapy and followed up with oral therapy for 5 days. The third group
      received the same doses of tropisetron along with dexamethasone before cisplatin
      and twice daily thereafter. The authors randomized 301 episodes. The patient
      characteristics were well balanced between the three groups. Acute nausea and
      vomiting were completely prevented in almost two thirds of patients receiving
      metoclopramide and tropisetron plus dexamethasone. These results are
      significantly superior to those of tropisetron alone (p < 0.01). Similarly,
      delayed nausea and vomiting were significantly better controlled with
      metoclopramdie cocktail and tropisetron plus dexamethasone than with tropisetron
      alone. Side effects were generally mild; however, they were more frequent with
      metoclopramide. The authors conclude that metoclopramide-based combination
      antiemetic therapy continues to be a cheaper alternative to serotonin antagonists
      and equally effective. Metoclopramide-based therapy, however, is more labor
      intensive, and issues related to administrative errors, side effects, and
      compliance gain increasing importance. The identification of persons at a higher
      risk for metoclopramide-induced side effects may help minimize the unacceptable
      consequences of therapy.

PMID- 10199445
TI  - Apocrine gland carcinoma of the axilla: review of the literature and
      recommendations for treatment.
AB  - Apocrine gland carcinoma is a rare form of sweat gland neoplasm with a
      distinctive cytologic appearance. Although the region of the axilla remains the
      most common site for these tumors, apocrine gland carcinoma of the anogenital
      region, eyelid, ear, chest, wrist, lip, foot, toe, and finger have been reported.
      Classically, these slow-growing lesions present as painless, colorless or
      reddish, firm or cystic nodules. More than half of the reported patients with
      apocrine carcinoma had lymph node metastases at the time of diagnosis. Wide local
      excision is standard therapy for these lesions. A therapeutic lymph node
      dissection is indicated for confirmed lymph node metastases and may have a role
      in the setting of a large or highly aggressive tumor with narrow surgical
      margins. Although apocrine gland carcinoma responds poorly to chemotherapy,
      adjuvant radiotherapy may be used in advanced local or regional disease. The
      authors describe a 69-year-old man with a large recurrent apocrine gland
      carcinoma of the axilla treated with en bloc excision with axillary dissection
      and offer a pertinent review of the English literature and recommendations for
      treatment.

PMID- 10199446
TI  - Adjuvant dose-intense chemotherapy with peripheral blood stem cell support in
      stage II-III breast cancer with five to nine involved axillary lymph nodes.
AB  - The purpose of this study is to determine outcomes for patients with high-risk
      nonmetastatic breast cancer undergoing high-dose chemotherapy with peripheral
      blood stem cell support. Forty-three patients with stage II-III disease, five to
      nine positive axillary lymph nodes, and a median age of 44 years (range, 27-60
      years) were enrolled in a study that included: 1) standard dose doxorubicin, 5
      fluorouracil, and methotrexate adjuvant therapy; 2) cyclophosphamide, etoposide,
      filgrastim, and peripheral blood stem cell harvest; and 3) high-dose
      cyclophosphamide, thiotepa, and carboplatin (CTCb) followed by peripheral blood
      stem cell infusion. All 43 patients received doxorubicin, 5-fluorouracil, and
      methotrexate, 42 (98%) received etoposide, and 41 (95%) received CTCb. Thirty-two
      patients (74%) are alive, 28 (65%) without relapse at a median of 55 months
      (range, 41-87 months). Two died (5%) of treatment-related causes, (subclavian
      catheter complication after etoposide and late radiation pneumonitis), and nine
      other deaths (21%) were associated with recurrent breast cancer. The
      probabilities of overall and event-free survival at 4 years were 0.77 and 0.67,
      respectively, compared with 0.82 and 0.69, respectively, for 72 similar patients
      with 10 or more positive axillary nodes receiving the same sequence of therapy.
      Thus, patients with five to nine positive axillary lymph nodes have a similar
      risk of failure after high-dose chemotherapy and peripheral blood stem cell
      support as patients with 10 or more positive axillary lymph nodes.

PMID- 10199447
TI  - Stereotactic Irradiation: potential new treatment method for brain metastases
      resulting from ovarian cancer.
AB  - Stereotactic irradiation (radiosurgery) is a method of precisely focusing well
      defined beams of radiation at small intracranial targets. The technique has been
      applied to the treatment of brain lesions that are benign (e.g., arteriovenous
      malformations, meningiomas, pituitary adenomas) and malignant (e.g., gliomas,
      metastases). This paper introduces preliminary data suggesting the possible value
      of radiosurgery in the management of ovarian cancer metastatic to the brain.
      Among 32 women with ovarian cancer metastatic to the brain treated with whole
      brain irradiation, nine (29%) experienced a complete radiographic response,
      compared with two of the five patients (40%) treated with radiosurgery. The 2
      year survival rate was 60% among those treated with radiosurgery and 15% among
      those who received whole brain irradiation without radiosurgical boost.
      Stereotactic irradiation may be of clinical benefit to select patients with brain
      metastases resulting from ovarian cancer. A prospective randomized trial has been
      implemented by the Radiation Therapy Oncology Group (RTOG 95-08) to determine
      whether such observations are reproducible on a national scale.

PMID- 10199448
TI  - Energy and applicator size and shape used in over 800 intraoperative electron
      beam therapy fields.
AB  - Intraoperative radiotherapy is a treatment option for some patients with locally
      advanced malignancies. This report updates the Mayo Clinic experience in more
      than 800 patients by analyzing the use of electron energy and cone size and shape
      by disease site between 1981 and 1996.

PMID- 10199449
TI  - Low-grade fibromyxoid sarcoma: clinicopathologic case report with review of the
      literature.
AB  - Low-grade fibromyxoid sarcoma is a rare, benign-appearing soft tissue neoplasm
      with an aggressive clinical course characterized by multiple local recurrences
      over several years, with ultimate spread to lung and occasionally to bone. Thus
      far, a total of 24 cases of low-grade fibromyxoid sarcoma have been reported in
      the literature. The authors present an additional case that grossly and
      microscopically emphasizes a pronounced lobular pattern of contrasting areas of
      cellularity showing high proliferative activity, as demonstrated by a
      proliferation marker, Ki 67 with MIB-1, and hypocellular areas with prominent
      myxoid component and abundant collagen fibrils. There was predominance of
      delicate capillary-sized stromal vessels with collagenized walls in both cellular
      and myxoid areas. The unusual features in this case were osseous metaplasia,
      prominent intranuclear pseudoinclusions, DNA tetraploidy, and membrane-bound
      intracytoplasmic fat vacuoles. The immunoprofile and cytologic and
      ultrastructural features are described. After the excision of the tumor, the
      patient was treated with radiotherapy without chemotherapy. The patient has been
      observed for 26 months and is alive without the evidence of disease. The
      postoperative follow-up with axial computed tomography at 24 months showed no
      evidence of disease, except postsurgical fibrotic changes.

PMID- 10199450
TI  - Pilot trial of infusional 5-fluorouracil, interleukin-2, and subcutaneous
      interferon-alpha for advanced renal cell carcinoma.
AB  - The authors developed an outpatient, three-drug combination regimen for advanced
      renal cell carcinoma. Treatment was administered for 5 days each week for 4
      weeks, followed by 2-week rests. Each weekly treatment consisted of 5
      fluorouracil 1,750 mg/m2 continuous intravenous infusion for 24 hours followed by
      interleukin-2 6 mIU/m2 per day continuous intravenous infusion for 4 days, and
      interferon-alpha2b 6 mU/m2 subcutaneously on days 1, 2, and 5. This trial was
      undertaken to assess tolerability to this regimen and obtain a preliminary
      assessment of its effectiveness. Most patients required some dose adjustments
      (especially of cytokines), treatment interruptions, or both. Toxicities were as
      would be expected from individual drug profiles with only mild to moderate
      hematologic toxicities. Among 16 patients with renal cell carcinoma treated, four
      had major (clinical partial response) responses, one of which was demonstrated to
      be a pathologic clinical response after surgical resection of a residual mass.
      Estimated median survival time of all patients was 93 weeks. Response and
      survival were correlated with known clinical risk factors. Responding patients
      were noted to be significantly older in age (X = 61.75 years) than nonresponders
      (X = 48.92 years). There was no correlation between age and other clinical risk
      factors, treatment tolerance, or survival. The authors conclude that this three
      drug regimen is a practical, tolerable, and promising regimen for further study
      in renal cell carcinoma.

PMID- 10199451
TI  - Single-agent paclitaxel in patients with metastatic breast cancer receiving high
      dose chemotherapy with peripheral blood stem cell support.
AB  - The purpose of this trial was to determine the effects of paclitaxel in patients
      with newly diagnosed metastatic breast cancer scheduled to receive high-dose
      chemotherapy with peripheral blood stem cell support. Eighty-four patients
      received anthracycline-based induction and two doses of paclitaxel at 170 mg/m2
      (n = 52) or 250 mg/m2 (n = 32). Eighty-two (98%) received cyclophosphamide and
      etoposide (n = 50) or paclitaxel and cyclophosphamide (n = 32) with granulocyte
      colony-stimulating factor for mobilization of peripheral blood stem cells, and 79
      (94%) received cyclophosphamide, thiotepa, and carboplatin with peripheral blood
      stem cell support. One patient (1%) died of infection and 56 (67%) died of
      progressive disease. For patients with measurable disease, the complete response
      rate was 21% after induction and 29% after paclitaxel (p = 0.54). Results were
      compared with those of 125 patients who received the same sequence of therapy
      without paclitaxel. The complete response rate after high-dose chemotherapy was
      54% for patients receiving paclitaxel and 62% for those not receiving paclitaxel
      (p = 0.60). The probabilities of overall survival and event-free survival at 3
      years for patients receiving paclitaxel were 46% and 24%, respectively, compared
      with 54% and 22%, respectively, for patients not receiving paclitaxel (p = 0.62).
      Further trials evaluating this dose and schedule of paclitaxel in patients with
      metastatic breast cancer receiving high-dose chemotherapy are not warranted.

PMID- 10199452
TI  - Phase II North Central Cancer Treatment Group study of 2-cholorodeoxyadenosine in
      patients with recurrent glioma.
AB  - There is no standard treatment for patients with recurrent gliomas, and their
      prognosis remains poor. 2-Chlorodeoxyadenosine is a purine analogue that has
      significant activity in many low-grade lymphoproliferative disorders. The authors
      conducted a phase II study to determine the efficacy of 2-chlorodeoxyadenosine in
      patients with recurrent gliomas. Patients with a histologically confirmed primary
      brain tumor with evidence of progression after radiation therapy were eligible.
      Protocol treatment consisted of 2-chlorodeoxyadenosine 7.0 mg/m2 intravenously on
      days 1 through 5 every 28 days. For those with a history of prior nitrosourea
      therapy, the dose of 2-chlorodeoxyadenosine was reduced to 5.6 mg/m2 on days 1
      through 5. Treatment was continued until progression or a maximum of 12 cycles.
      Fifteen patients with recurrent astrocytomas or oligoastrocytomas of all grades
      were entered in the study. Treatment was well tolerated. Major toxicities were
      myelosuppression and neurotoxicity. No responses were seen. The authors conclude
      that although 2-chlorodeoxyadenosine is well tolerated, no demonstrable activity
      in patients with recurrent gliomas was established.

PMID- 10199453
TI  - Anaphylaxis from intraperitoneal infusion of cisplatin: a case report.
AB  - Anaphylactic reactions to platinum compounds and paclitaxel are well-recognized
      complications during their systemic administration. Although there have been
      reports describing anaphylaxis during intravesical instillation of
      chemotherapeutic agents, to the best of the authors' knowledge, no
      hypersensitivity reactions after intraperitoneal administration of
      chemotherapeutic drugs has been reported in the English literature. The authors
      report an unusual case of anaphylaxis occurring in a 33-year-old woman who has
      been treated with paclitaxel and cisplatin for ovarian cancer. She developed a
      hypersensitivity reaction during her ninth cycle of chemotherapy, immediately
      after institution of intraperitoneal infusion of cisplatin. It is important to be
      aware of the possibility of anaphylaxis during chemotherapy administration other
      than the systemic route so that appropriate premedication or effective treatment
      can be promptly instituted.

PMID- 10199454
TI  - Soft tissue masses of the chest wall and axilla: has metastatic melanoma been
      considered?
AB  - Isolated axillary and chest wall soft tissue masses are an uncommon presentation
      of metastatic cancer. The authors present three patients in whom malignant
      melanomas metastatic to these sites had been misdiagnosed, leading to
      inappropriate oncologic treatment planning in all three cases. The presumed
      diagnoses, even after fine-needle aspiration or trucut biopsies, were soft-tissue
      sarcoma (n = 2) and undifferentiated breast cancer (n = 1). The combination of
      taking a thorough history and performing proper immunohistochemical analysis of
      the biopsy material would have suggested the presence of malignant melanoma in
      all cases. As the disease appeared locoregionally limited in all patients,
      radical surgical resection with extended lymphadenectomy was performed without
      significant dysfunction of the upper extremity. One patient agreed to
      postoperative immunotherapy with interferon-alpha. Two patients are currently
      alive 17 and 14 months after operation. One patient was found to have systemic
      recurrence at 5 months, one experienced two isolated local recurrences in a prior
      operative site that were amenable to reresection and presently has no evidence of
      disease 12 months after resection, and one patient remains free of disease at 14
      months. Clinical presentation, suggested diagnostic workup, and therapeutic
      implications are discussed to avoid misdiagnoses in this setting of possible
      clinical presentations of metastatic melanoma.

PMID- 10199455
TI  - Expression of risk factors for breast cancer in women younger than 49.
AB  - The definition of women younger than 49 who are at increased risk for breast
      cancer would enable intensified efforts in surveillance and use of preventive
      measures for this group. In this survey of 32,123 members of Health Net, an
      increased risk for breast cancer was related to age, breast cancer in the
      immediate family (mother, sister), and previous biopsies for cystic lesions of
      the breast. No increased risk was related to menarche, nulliparity, first
      pregnancy after age 30, or breast feeding.

PMID- 10199456
TI  - Disseminated Langerhans cell histocytosis in children: treatment outcome.
AB  - Langerhans cell histiocytosis is an interesting disorder with a variety of
      presentations and variable outcomes. This study evaluates response to treatment,
      recurrence, and survival in disseminated Langerhans cell histiocytosis treated at
      Regional Cancer Centre, Trivandrum, India from 1983 through 1994. Thirty-five
      patients with disseminated Langerhans cell histiocytosis were seen. Six had group
      A disease, 21 had group B disease, and eight had group C disease. In group A,
      five of six patients are disease free at a median follow-up of 48 months. Two had
      recurrence after initial treatment, which was salvaged. In group B, 13 of 15
      patients had complete response after chemotherapy, nine of whom experienced
      recurrence later. Three of five patients who received irradiation alone
      experienced recurrence. One died of progressive disease. Two patients were lost
      to follow-up. Seventeen of 20 are alive with median follow-up of 67 months. In
      group C, one of eight patients are alive after multiple recurrences. Of the
      surviving patients, 29% had significant sequelae. In summary, group A and B
      patients do well with treatment, and most of the recurrences can be salvaged. A
      significant proportion of patients have sequelae. Newer aggressive protocols must
      be developed for treating group C patients. Measures to prevent sequelae must
      also be developed.

PMID- 10199457
TI  - Role of radiation therapy in the management of cutaneous malignant melanoma.
AB  - Traditionally, cutaneous malignant melanoma is regarded as a radioresistant
      tumor. Recently, however, an increasing number of clinical studies have refuted
      this notion. The authors examined the role of radiation therapy in the palliative
      and/or adjuvant treatment of cutaneous malignant melanoma. The records of 69
      patients with cutaneous malignant melanoma were reviewed. Twenty-five patients
      with extensive regional lymph node involvement received adjuvant radiation
      therapy after primary surgical treatment, and the remainder received palliative
      radiation therapy. The therapeutic significance of fraction size was analyzed. In
      the palliative radiation therapy group, the response rate was 52% with a fraction
      size < or = 300 cGy and 35% with a larger fraction size (p > 0.05, NS). Local
      regional control rates after adjuvant radiation therapy using conventional
      fractionation and larger fraction size were 87% and 82%, respectively (p > 0.05,
      NS). Radiation therapy is effective in the management of cutaneous malignant
      melanoma. It plays an important role in the palliation of metastatic disease and
      as an adjuvant treatment. No advantage in using a large fraction size over
      conventional dose schedules was found.

PMID- 10199458
TI  - Complete clinical remission in a patient with advanced pancreatic cancer using
      mitomycin C-based chemotherapy: the role of adjunctive heparin.
AB  - In a patient with advanced pancreatic cancer, with a hypercoagulable state, a
      complete clinical response was obtained with a mitomycin-based regimen plus
      adjunctive heparin. The patient converted from a partial response to a complete
      response with the addition of heparin, raising the possibility that heparin was
      somehow involved in the process. Recent studies have reported prolongation of
      survival in patients with cancer who were given heparin along with chemotherapy.
      The known antiangiogenic and antiproliferative action of heparin may explain this
      possible synergism. If heparin is, in fact, synergistic with cytotoxic cancer
      drugs, a fertile field of investigation is open to cooperative groups, especially
      because long-term heparin therapy is now feasible and safe, the low-molecular
      weight heparins even more so.

PMID- 10199459
TI  - Late recurrence of childhood acute lymphoblastic leukemia.
AB  - Late relapse of childhood lymphoblastic leukemia 10 years after the end of
      treatment is rare. A young woman whose acute lymphoblastic leukemia recurred 11
      years after the end of treatment for acute lymphoblastic leukemia is described,
      and the literature on late relapse of childhood acute lymphoblastic leukemia is
      reviewed.

PMID- 10199460
TI  - Therapy of desmoid tumors and fibromatosis using vinorelbine.
AB  - In patients with either desmoids or fibromatosis who do not tolerate vinblastine
      and methotrexate because of neurotoxicity, the combination of vinorelbine and
      methotrexate can be substituted in most. Patients with the same condition who had
      not been previously treated with a combination of vinblastine and methotrexate
      responded well to the combination of vinorelbine and methotrexate, with
      significantly less neurotoxicity and a similar objective and subjective response
      rate. Sixty percent of patients had either a substantial partial remission or a
      complete remission. In no patients did the disease progress while they were
      receiving this therapy. Symptomatic relief, primarily of pain, occurred in 80% of
      patients. While minimal neurotoxicity was seen in 16% of these patients, it did
      not interfere with the completion of therapy. The combination of vinorelbine and
      methotrexate appears to be active in the treatment of both desmoid tumors and
      fibromatosis and is associated with significantly less neurotoxicity then that
      seen with the combination of vinblastine and methotrexate. No long-term toxicity
      was seen in any patient in this series.

PMID- 10199461
TI  - Treatment with a nonanthracycline regimen in advanced breast cancer: vinorelbine,
      cyclophosphamide, and 5-fluorouracil with folinic acid.
AB  - The efficacy of combination therapy with vinorelbine, cyclophosphamide, and 5
      fluorouracil was assessed in women who had received no prior therapy for locally
      advanced or metastatic breast cancer. Sixty patients with metastatic breast
      cancer who had finished any adjuvant therapy at least 6 months previously and who
      had not received treatment for advanced disease were entered onto the study. The
      schedule consisted of vinorelbine (Navelbine, Pierre Fabre Medicament) 25 mg/m2
      on days 1 and 8, cyclophosphamide 500 mg/m2 on day 1, and 5-fluorouracil 500
      mg/m2 followed by folinic acid 200 mg/m2 on days 1 and 8. Treatment was repeated
      every 21 days up to a maximum of 8 cycles. Objective responses were observed in
      27 of 60 patients (45%; CI95 32.4-57.6) including 4 complete responses (6.7%;
      CI95 0-13) and 23 partial responses (38.3%; CI95 22.5-54.1). The responses were
      achieved in both visceral and nonvisceral sites and at the same rate for patients
      with multiple sites of disease. Neutropenia was dose limiting, with 40% of
      patients affected at grade 3 or 4, while other hematologic and nonhematologic
      toxicity was very mild. This schedule achieves good levels of response without
      the use of an anthracycline, so it is suitable either for patients who have been
      extensively exposed to anthracyclines during adjuvant therapy or for those who
      have other contraindications to their use.

PMID- 10199462
TI  - Lung carcinoma presenting as metastasis to intracranial meningioma: case report
      and review of the literature.
AB  - Tumor-to-tumor metastasis is rare. The authors report a case of a 52-year-old man
      with a 1-year history of a right parasaggital meningioma, whose clinical signs
      were consistent with enlarging meningioma. In preparation for surgery, the
      routine preoperative chest radiograph revealed a lung mass. Fine-needle
      aspiration of the mass revealed adenocarcinoma. The patient underwent surgical
      excision of the intracranial mass, which was thought to be a meningioma. However,
      pathologic examination revealed a transitional meningioma extensively infiltrated
      with deposits of metastatic carcinoma from the patient's primary lung tumor.
      Metastasis to meningioma was therefore responsible for the rapid enlargement of
      the long-standing meningioma, and caused the first clinical manifestation of
      primary lung carcinoma. Recurrent metastasis developed at the surgical site 5
      weeks later, requiring surgical excision and postoperative radiation to prevent
      further recurrence. This is a highly unusual presentation for lung carcinoma and,
      to the authors' best knowledge, is the first such case reported. A review of the
      published literature revealed 20 other cases of lung carcinoma metastatic to
      meningioma, which were incidentally discovered on surgery or autopsy.

PMID- 10199463
TI  - Induction platinum-based chemotherapy followed by radical hyperfractionated
      radiotherapy with concurrent chemotherapy in the treatment of locally advanced
      non-small-cell carcinoma of the lung.
AB  - This study evaluated tolerance, local control, and short-term survival in
      patients with locally advanced non-small-cell lung carcinoma treated with
      induction chemotherapy followed by radical hyperfractionated radiotherapy with
      concurrent chemotherapy. Thirty-one patients with stage IIIa (N2) or IIIb tumors
      were treated with cis-platinum-based induction chemotherapy for 1 to 4 courses
      followed by radical hyperfractionated radiotherapy (69.6 Gy) with concurrent
      chemotherapy given at the beginning and end of radiotherapy. Induction
      chemotherapy produced no complete responses and 18 (58%) partial responses. After
      completion of radiotherapy, 4 patients had complete response (13%) and 23
      patients (74%) partial response. The patterns of failure were as follows:
      intrathoracic, 6 patients (22%); intrathoracic + distant metastasis, 6 patients
      (22%); distant metastasis without thoracic failure, 5 patients (19%). Six
      patients of the 12 with intrathoracic failure experienced in-field radiotherapy
      pure local failure. At the time of this analysis, 10 patients were alive and well
      (4 complete and 6 partial responders). Actuarial survival projected at 39 months
      is 35%. No benefit was observed for those patients responding to induction
      chemotherapy. Toxicity was as follows: grade III neutropenic fever in 4 patients
      (13%), grade IV neutropenia in 13 patients (42%), pneumonia in 6 patients (19%),
      grade III esophagitis in 4 patients (13%) and severe clinical pneumonitis in 1
      patient (3%). Induction chemotherapy followed by chemoradiotherapy is feasible,
      and the preliminary results are encouraging. Complete response after radiotherapy
      appeared to be related to short-term disease-free survival, and decisions based
      on the response to chemotherapy may be equivocal.

PMID- 10199464
TI  - Durable clinical and pathologic response of hepatocellular carcinoma to systemic
      and hepatic arterial administration of platinol, recombinant interferon alpha 2B,
      doxorubicin, and 5-fluorouracil: a communication.
AB  - The case described here illustrates the antitumor activity of a four-drug
      systemic combination chemobiotherapy with platinol, recombinant interferon alpha
      2b, doxorubicin (Adriamycin), and 5-fluorouracil (5-FU) (PIAF) in a patient with
      diffuse hepatocellular carcinoma involving the liver and lungs.

PMID- 10199465
TI  - Microangiopathic hemolytic anemia as an early predictor of recurrence in gastric
      cancer.

PMID- 10199466
TI  - Hodgkin's disease expressing follicular dendritic cell marker CD21 without any
      other B-cell marker: a clinicopathologic study of nine cases.
AB  - Reed-Sternberg (RS) and Hodgkin's (H) cells are considered to be the neoplastic
      cells in Hodgkin's disease (HD). Although most data suggest their lymphoid
      origin, the nature of these cells still remains a subject of controversy.
      Recently, a number of RS cells have been found to express an antigen that is also
      present on follicular dendritic cells (FDCs), asserting FDCs as the possible
      progenitor cells of H-RS cells. This prompted us to investigate whether these
      CD21-positive cases had distinct clinicopathologic characteristics. In a series
      of 94 examined cases of HD, we identified 9 CD21-positive ones (4 of 37 cases of
      nodular sclerosis, 1 of 41 mixed cellularity, and 4 of 12 lymphocyte depletion
      HD) without any other B-cell marker on paraffin sections. The patients varied in
      age from 16 to 82 years (median, 50 years) and included six men and three women.
      They had superficial or mesenteric lymphadenopathy without hepatosplenomegaly.
      Peripheral blood leukocytosis was seen in three patients. The clinical course was
      indolent, and all patients but one achieved an initial complete response with HD
      based treatment regimens, although three of them relapsed. Morphologically, two
      subgroups could be delineated. Six of the cases were characterized, besides by
      the classic RS cells, by a varying number of the cells with the distinctive
      walnutlike or cerebrumlike nuclei and cytologically with cytoplasmic processes.
      Their fine structural examination also revealed villous processes, but no
      desmosomes. The other three cases had multinucleated RS cells often with
      triangular nuclei, but not cytoplasmic processes. The percentage of CD21-positive
      tumor cells ranged from less than 10% to 60% among the H-RS cells. These RS cells
      were positive for CD30 (9 of 9), CD15 (7 of 9), CD68 (1 of 8), fascin (8 of 8), S
      100 protein (1 of 7), and epithelial membrane antigen (2 of 8) on paraffin
      sections. Notably, of eight cases examined on frozen sections, two showed
      immunostaining for DRC1, CD35, R4/23, and Ki-M4p. Only CD35 was also detected in
      the other two cases. Genotypic investigation showed germline configuration of the
      T-cell receptor beta and gamma chain genes and the immunoglobulin heavy chain
      gene in all eight cases examined. In situ hybridization showed Epstein-Barr virus
      sequences in four cases, three of which were examined by the terminal region
      analysis and showed the Epstein-Barr virus to be monoclonal. We concluded that in
      a small proportion (9.6%) of HD, H-RS cells might be derived from FDCs and that
      they appear to represent a distinct pathologic variant based on morphologic and
      phenotypic traits within the framework of HD.

PMID- 10199467
TI  - Interstitial cells of Cajal as precursors of gastrointestinal stromal tumors.
AB  - Interstitial cells of Cajal (ICC) are implicated in the regulation of gut
      peristalsis and are immunostained by antibodies against Kit (CD117), a tyrosine
      kinase receptor. Most gastrointestinal mesenchymal tumors (GIMTs) are of
      uncertain histogenesis, although many are CD34-positive. CD34 was found to
      colocalize with vimentin (Vim) and the Kit-positive networks of cells within and
      around neural plexi, indicating that ICC can be Vim- and CD34-positive. ICCs
      appear to be the only Kit+CD34+Vim+ cell in the gut. Formalin-fixed, paraffin
      embedded tissues from 43 GIMTs were immunostained for Kit, CD34, Vim, PGP 9.5
      (PGP, a neural marker), muscle-specific actin (MSA), and other markers including
      desmin (Des). Eight tumors were myoid (MSA+Des+Vim-Kit-CD34-), and one was a
      schwannoma (PGP+S100+Vim+Kit-CD34-), but 34 tumors were of uncertain histogenesis
      (gastrointestinal stromal tumors, GIST), exhibiting neither a complete myoid nor
      a schwannian immunophenotype. All 34 were Vim+, and 33/34 were either Kit (n =
      30) or CD34 (n = 23) immunoreactive. Of these 34 GIST, 24 were negative for all
      myoid and neural markers, 6 were PGP+S100-, and 4 were MSA+Des-. The
      Kit+CD34+Vim+ immunophenotype of GIST suggests that they originate from, or have
      differentiated into, ICC-like cells; the term ICC tumor (ICCT) is suggested. Kit
      is a more sensitive marker than CD34 for ICCT, but both are required in tumor
      identification. All clinically malignant GISTs were pathologically malignant
      (size, mitoses) but also showed loss of either CD34 or Kit. "Blind" examination
      of electron micrographs in 10 tumors showed them to be heterogeneous. Some had
      features seen in normal ICC, but cells could not be positively identified as
      being adult ICC. GIMT may therefore be classifiable into those with pure myoid,
      schwannian (or neural) differentiation, but the majority are of ICC origin or
      show ICC differentiation immunophenotypically (ICCT).

PMID- 10199468
TI  - Allergic esophagitis in children: a clinicopathological entity.
AB  - Infiltration of esophageal epithelium by eosinophils is seen in reflux
      esophagitis and allergic gastroenteritis. This study was performed to identify
      differences between patients with acid reflux esophagitis and those with non-acid
      reflux, possibly allergic, esophagitis. Intraepithelial eosinophils were
      demonstrated in posttherapy esophageal biopsy specimens in 28 children treated
      for gastroesophageal reflux disease (GERD). These patients were divided into
      three groups based on their response to treatment and the results of esophageal
      pH probe monitoring. Eleven patients (Group A) had incomplete clinical response
      and normal pH probe monitoring results. Ten patients (Group B) had incomplete
      response but did not have pH probe monitoring. These two groups formed the index
      population. Seven patients (Group C) had clinical improvement with GERD therapy
      and abnormal pH probe monitoring characteristic of GERD; they constituted the
      control population. Clinical, laboratory, and pathologic features were evaluated
      to detect differences between index and control populations. Dysphagia, food
      impaction, failure to thrive, peripheral eosinophilia, and abnormal allergen skin
      test results were detected only in Group A and B patients. Biopsy specimens of
      the distal 9 cm of the esophagus, after GERD therapy, contained larger numbers of
      eosinophils in Groups A and B than in Group C as shown on high-power fields (HPF)
      (A: 31/HPF +/- 19.5; B: 28/HPF +/-23.7; versus C: 5/HPF +/-6.7; p = 0.009).
      Eosinophil aggregates were identified only in Groups A and B (p = 0.07).
      Eosinophils located preferentially in the superficial layers of the squamous
      epithelium were noted only in Groups A and B (p = 0.02). Group A and B patients
      demonstrated clinical improvement when given antiallergic therapy. The authors
      identified a group of pediatric patients characterized by an allergic history,
      lack of adequate response to GERD therapy, normal esophageal pH probe monitoring
      results, and large numbers of eosinophils in esophageal biopsy specimens obtained
      after GERD treatment. On the basis of these features, the authors propose that
      these patients represent examples of allergic esophagitis.

PMID- 10199469
TI  - Ovarian serous borderline tumors with micropapillary and cribriform patterns: a
      study of 40 cases and comparison with 44 cases without these patterns.
AB  - A group of investigators have proposed that the presence of micropapillary or
      cribriform patterns within ovarian serous tumors diagnosed as borderline
      according to World Health Organization (WHO) criteria identifies a subset of
      these neoplasms that are apt to be associated with invasive peritoneal implants
      and therefore should be designated as "micropapillary carcinoma." The authors of
      the current article identified 40 serous borderline tumors that showed one or
      both of these patterns, using the earlier investigators' published criteria for
      so-called micropapillary carcinoma, and compared them with 44 tumors that lacked
      these patterns (controls). Twenty-six patients with micropapillary tumors were
      aged 21 to 76 years (mean 38); 11 with cribriform tumors were aged 34 to 79 years
      (mean 60); and 3 with tumors having both patterns were aged 21 to 58 years (mean
      38); the control patients were aged 22 to 83 years (mean 54). An advanced stage,
      bilaterality, and ovarian surface growth were features of the "micropapillary"
      tumors more often than of the control tumors. Except for a postoperative death
      related to sepsis, all 11 patients with Stage I tumors with either or both
      patterns who were followed until their death, or for at least 5 years (mean 7.9
      years), survived without evidence of disease; a twelfth patient had a recent
      removal of recurrent pelvic tumor at 2.8 years and was alive at 3.3 years. Six of
      the eight patients with Stage II or III tumors with either or both patterns who
      were followed for at least 5 years (mean 7.5 years) survived disease-free. No
      deaths from tumor or progressive recurrences occurred in 27 control cases with 5
      14 (mean 7.9) years of follow-up data. The two tumor-related deaths in the entire
      series, one from a micropapillary tumor and one from a cribriform tumor, occurred
      in patients who had Stage III tumors with invasive peritoneal implants. No
      patient with "micropapillary" tumors and noninvasive implants had progressive
      disease. Two women with "micropapillary" tumors and two control subjects had
      stable recurrent tumor or a newly developed tumor in a contralateral ovary that
      had been spared during the initial operation. Our findings confirm those of
      previous investigators that noninvasive serous tumors with a micropapillary or
      cribriform pattern or both patterns may be accompanied by invasive peritoneal
      implants more often than tumors without such patterns and that in such cases the
      disease is likely to be progressive and fatal. Since so-called micropapillary
      carcinomas lack obvious stromal invasion within the ovary, and their prognosis
      when they spread to the peritoneum is much closer to that associated with typical
      Stage II and III serous borderline tumors than to that associated with similarly
      staged serous carcinomas, the authors believe that this newly described category
      of tumors should remain as a subset within the borderline category, with a
      notation that their prognosis is poor if they are associated with invasive
      peritoneal implants.

PMID- 10199470
TI  - Mucinous cystic tumors of the pancreas: clinicopathological features, prognosis,
      and relationship to other mucinous cystic tumors.
AB  - The clinicopathological features of 56 patients with mucinous cystic tumors
      (MCTs) of the pancreas were studied. Particular attention was paid to the
      prognosis of MCTs and the relationship to their ovarian, hepatic, and
      retroperitoneal counterparts. To distinguish MCTs from pancreatic intraductal
      papillary-mucinous tumors, MCTs were defined as tumors lacking communication with
      the duct system and containing mucin-producing epithelium, usually supported by
      ovarian-like stroma. All 56 tumors occurred in women (mean age 48.2 years) and
      were preferentially (93%) located in the body and tail of the pancreas. In
      accordance with the WHO classification, MCTs were divided into adenomas (n = 22),
      borderline tumors (n= 12), and noninvasive and invasive carcinomas (n = 22).
      Survival analysis revealed the extent of invasion to be the most significant
      prognostic factor (p<0.0001). Malignancy correlated with multilocularity and
      presence of papillary projections or mural nodules, loss of ovarian-like stroma,
      and p53 immunoreactivity. Stromal luteinization with expression of tyrosine
      hydroxylase, calretinin, or alpha inhibin was found in 66% of the cases. We
      conclude that the biologic behavior of MCTs is predictable on the basis of the
      extent of invasion. The similarities (i.e. gender, morphology, stromal
      luteinization) between pancreatic MCT and its ovarian, hepatobiliary, and
      retroperitoneal counterparts suggest a common pathway for their development.

PMID- 10199471
TI  - Biopsy diagnosis of colitis: possibilities and pitfalls.
AB  - The histopathologic diagnosis of inflammation is common in colorectal biopsies
      but is of limited value, if not further specified. We reviewed 280 endoscopic
      colorectal biopsy specimens for nonneoplastic disease from 100 consecutive
      patients in order to assess (a) the frequency of inflammation in excess of the
      physiologic infiltrate, (b) the frequency with which the cause of the
      inflammation could be specified, and (c) the interobserver variability in
      diagnosing inflammation. Based on the reviewers' impression, each case was
      classified into one of three categories: (I) normal or nonspecific change, (II)
      nonspecific inflammation, and (III) inflammation suggestive or diagnostic of
      specific cause. Inflammation was diagnosed in 68% of cases. The majority of these
      cases (75%) showed features typically associated with specific types of colitis,
      including Crohn's disease (n = 16), ulcerative colitis (n = 13), inflammatory
      bowel disease not otherwise specified (n = 5), infectious colitis (n = 6),
      ischemic colitis (n = 4), solitary rectal ulcer syndrome (n = 3), radiation
      colitis (n = 2), and lymphocytic colitis (n = 2). Interobserver variability was
      greatest in biopsy specimens interpreted by the reviewers as normal or showing
      nonspecific changes, most of which had been diagnosed as mild inflammation by the
      original pathologists. Etiologic classification of colitis was lacking in 59% of
      the cases interpreted by the reviewers as suggestive or diagnostic of a specific
      cause. We conclude that (a) the majority of colorectal biopsy specimens from
      patients with nonneoplastic disease in this series show inflammation, (b) the
      majority of such cases allow a specific cause of colitis to be suggested or
      firmly diagnosed, and (c) pathologists tend to overdiagnose the physiologic
      inflammatory infiltrate as evidence of colitis and underdiagnose specific
      etiologic types of colitis.

PMID- 10199472
TI  - Benign schwannoma of the digestive tract: a clinicopathologic and
      immunohistochemical study of five cases, including a case of esophageal tumor.
AB  - We report five cases of schwannomas of the digestive tract. The patients were two
      men and three women, whose ages ranged from 56 to 74 years. Three cases arose in
      the stomach, one in the ascending colon, and one in the esophagus; the latter was
      a hitherto unreported location for this tumor. The schwannomas ranged from 2 to
      11 cm in diameter. They were well circumscribed but not encapsulated, with
      interlacing bundles of spindle cells, nuclear atypia and no mitosis, interspersed
      with collagenous strands. Inflammatory cells were scattered throughout the tumors
      and a peripheral cuff of lymphoid aggregates was observed in all cases.
      Intracellular periodic acid-Schiff (PAS)-positive crystalloids were found in
      three cases; no skeinoid fibers were seen. A diffuse and intense positivity for
      vimentin and S-100 protein was detected in all five cases together with a
      variable and sometimes focal positivity for glial fibrillary acidic protein and
      neuron-specific enolase. None of the tumors showed expression of CD34 or the
      smooth muscle antigens tested. The four cases with a sufficient follow-up had a
      favorable outcome without any recurrence or metastasis. The morphologic and
      immunohistochemical features of digestive schwannomas were compared with those of
      other gastrointestinal stromal tumors. Schwannomas have many differences.
      Digestive schwannomas can be readily recognized on histologic and
      immunohistochemical examination. They are spindle cell tumors without epithelioid
      features, with a peripheral cuff of lymphoid tissue. Specific intracellular
      needle-shaped PAS-positive crystalloids are found in some cases, whereas skeinoid
      fibers are not. These tumors always express S-100 protein in a diffuse and strong
      manner, and they express glial fibrillary acidic protein but not express CD34.
      Digestive schwannomas usually are gastric tumors and have never been reported in
      the small bowel. They pursue a benign course and are far rarer than
      gastrointestinal autonomic nerve tumors.

PMID- 10199473
TI  - Diffuse glomerular basement membrane lamellation in renal allografts from
      pediatric donors to adult recipients.
AB  - The transplantation of kidneys from pediatric cadaveric donors into adult
      recipients is performed in many centers. However, some studies indicate that the
      outcome of such renal transplants may be inferior compared with that of adult
      donors, particularly if the donor is an infant. Morphologic studies of failed
      pediatric donor kidneys in adult recipients describe various degrees of segmental
      or global glomerular sclerosis. The authors have performed ultrastructural
      examinations on such transplants and have identified six cases with diffuse
      irregular lamellation of the glomerular basement membrane (GBM), a change that
      may develop as early as 10 weeks after transplantation. The age of all donors was
      < or =6 years; three were infants. The incidence of the lesion was 9% at our
      institution in renal transplant patients who received a graft from donors <10
      years old. Diffuse GBM lamellation has not been found in renal transplants from
      adult donors. Light microscopy showed various degrees of diffuse mesangial
      expansion, usually with segmental glomerular sclerosis. The patients had severe
      proteinuria. While recurrent focal segmental glomerular sclerosis (FSGS) has to
      be excluded, such diffuse GBM lamellation is generally not seen in recurrent FSGS
      cases. The pathogenesis of the lesion is most likely related to hyperperfusion
      injury of small pediatric donor kidneys grafted into adult recipients.

PMID- 10199474
TI  - Natural history of urothelial dysplasia of the bladder.
AB  - Urothelial dysplasia is the putative precursor of urothelial carcinoma in situ
      (CIS) and invasive urothelial carcinoma of the urinary tract. Urothelial
      dysplasia is frequently identified in patients with urothelial CIS and cancer.
      However, very little is known about the clinical presentation and natural history
      of urothelial dysplasia in the absence of urothelial CIS or invasive cancer. The
      authors studied 36 patients with isolated urothelial dysplasia at the Mayo Clinic
      between 1969 and 1984. None of these patients had previous or concurrent
      urothelial CIS or invasive cancer, and none received treatment for dysplasia. The
      histopathologic features of urothelial dysplasia were examined, and long-term
      clinical follow-up was obtained. Progression was defined as the development of
      urothelial CIS or carcinoma. The male-to-female ratio was 2.6:1, and the mean
      patient age at the time of diagnosis was 60 years (range 25-79). Urothelial
      dysplasia has a predilection for the posterior wall. Eleven patients had urinary
      irritative symptoms, 10 had hematuria, 3 had both irritative symptoms and
      hematuria, and 12 were found to have dysplasia incidentally. The mean follow-up
      was 8.2 years (range 0.1-25.5). Seven (19%) of 36 patients developed biopsy
      proven progression, including 4 with CIS and 3 with invasive cancer, and 1 of
      them died of bladder cancer. The intervals from diagnosis to progression ranged
      from 6 months to 8 years (mean 2.5 years). One of the remaining 29 patients had
      positive cytologic results 2.5 years after the initial diagnosis of dysplasia.
      The authors conclude that urothelial dysplasia is a significant risk for the
      development of CIS and invasive urothelial carcinoma, and patients with
      urothelial dysplasia should be followed up closely.

PMID- 10199475
TI  - Adenoid cystic and adenoid basal carcinoma of the uterine cervix: comparative
      morphologic, mucin, and immunohistochemical profile of two rare neoplasms of
      putative 'reserve cell' origin.
AB  - Adenoid cystic carcinomas (ACCs) and adenoid basal carcinomas (ABCs) are rare
      neoplasms of the uterine cervix that are currently regarded as distinct
      clinicopathologic entities. Accurate distinction between ABCs and ACCs is of
      clinical importance because of differences in their biological behavior. This
      study compares the morphologic, mucin, and immunohistochemical profiles of 18
      cervical ACCs, 8 ABCs, and 1 combined ABC-ACC. Serial sections from the 27 cases
      were stained with hematoxylin and eosin, periodic acid-Schiff-diastase,
      mucicarmine, and alcian blue and subjected to a panel of immunoperoxidase
      markers, namely, MNF116, CAM 5.2, CK7, CK20, epithelial membrane antigen,
      carcinoembryonic antigen (CEA), S-100, HHF 35, laminin, and type IV collagen. One
      ACC was also examined ultrastructurally. Almost all patients were postmenopausal
      black women. The distinction between ABC and ACC was best made morphologically.
      Divergent epithelial differentiation was seen in 18 cases (11 ACCs, 6 ABCs, and 1
      ABC-ACC). Six cases with intact surface epithelium showed a high grade squamous
      intraepithelial lesion. There was no significant difference in mucin staining.
      Both tumor types had a similar immunohistochemical profile, apart from type IV
      collagen and laminin staining, which occurred exclusively in relation to the
      extracellular basement membranelike material in the ACC. Eleven ACCs and three
      ABCs were S-100-positive, including the respective ACC and ABC components of the
      combined ABC-ACC. Eight of the S-100-positive neoplasms with ACC morphology also
      stained with HHF 35, suggesting myoepithelial differentiation. The latter was
      confirmed in one ACC examined ultrastructurally. The similar clinical profiles,
      apart from the different biological behavior, capacity for divergent
      differentiation, and the occurrence of ABC areas in some ACCs and vice versa
      suggest that these tumors may share a common histogenesis, forming part of a
      morphologic and biologic spectrum of basaloid cervical neoplasms of putative
      "reserve cell" origin. Circumstantial evidence suggests that ABC may be a
      precursor of cervical ACC.

PMID- 10199476
TI  - Histopathologic studies of colorectal postendoscopic resection sites: "skipping
      electrothermal injury" associated with endoscopic resection procedures.
AB  - To elucidate the pathologic changes due to endoscopic resection (ER), 32 post-ER
      sites in 24 surgically removed colorectal specimens and the previous ER specimens
      were examined. The depth of all the previous ER specimens was restricted to the
      submucosa, and all post-ER sites showed submucosal stromal changes of various
      degrees. Fourteen sites (43.8%) showed muscular or serosal changes. One of these
      lesions was considered to be a reaction to a tattoo agent, but all the other
      lesions were considered to represent skipping electrothermal injury caused by
      electrical current passing through the colorectal wall. The lesions consisted of
      muscular depletion in the inner layer of the muscularis propria (12 sites,
      37.5%), hemorrhage or fibrosis between the inner and outer layers of the
      muscularis propria (3 sites, 9.4%), and serosal changes (10 sites, 31.3%). These
      skip regions would be vulnerable to electrical current. These findings suggest
      that asymptomatic electrothermal injury associated with ER is frequent.
      Statistically, the electrothermal injury appeared to be related to the size of
      the previous ER specimens. However. these results also reveal that the ER of
      tissues <10 mm can cause electrothermal injury and can result in full-thickness
      necrosis.

PMID- 10199477
TI  - Dedifferentiation in adenoid cystic carcinoma of salivary gland: an uncommon
      complication associated with an accelerated clinical course.
AB  - Adenoid cystic carcinoma (ACC) of the salivary gland is generally an indolent
      tumor that pursues a protracted clinical course with recurrences and late
      metastasis. The authors report three cases of ACC with dedifferentiation to high
      grade malignant neoplasms. One patient developed dedifferentiated ACC ab initio,
      with extensive local disease and multiple lymph nodes metastases at first
      presentation, requiring mutilating surgery. Two patients had dedifferentiated ACC
      4 and 10 years, respectively, following excision of the initial uncomplicated
      ACC; both patients died within 1.5 years after recurrence. Histologically, the
      dedifferentiated component appeared as a distinct population of anaplastic cells
      with more abundant cytoplasm, irregular-shaped tumor islands infiltrating a
      desmoplastic stroma, and total loss of bicellular differentiation characteristic
      of ACC. The immunophenotypic profile was altered in comparison with the ACC, such
      as acquisition of strong staining for S100 protein and lack of a myoepithelial
      component in the two cases that were interpreted as being poorly differentiated
      adenocarcinoma. One case was a sarcomatoid neoplasm with focal myoepithelial
      features. Overexpression of p53 protein was demonstrated in the dedifferentiated
      component in one case, and overexpression of cyclin D1 was seen in two cases. The
      dedifferentiated component had a higher Ki67 index than did the ACC. To the
      authors' best knowledge, this report represents the first documentation of
      dedifferentiation as a form of tumor progression in ACC, which is associated with
      a sinister clinical outcome.

PMID- 10199478
TI  - Epstein-Barr virus-associated leiomyosarcoma of the thyroid in a child with
      congenital immunodeficiency: a case report.
AB  - We report an unusual case of multifocal leiomyosarcoma involving the thyroid
      gland, liver, and right lung in a child with congenital immunodeficiency disease.
      The smooth muscle nature of these neoplasms was confirmed by immunohistochemistry
      and electron microscopic studies. In situ hybridization showed large amounts of
      Epstein-Barr virus messenger RNA within the tumor cells. Although Epstein-Barr
      virus-associated smooth muscle tumors have been reported in children with AIDS
      and after organ transplantation, we are unaware of any case report in congenital
      immunodeficiency disease.

PMID- 10199479
TI  - Primary intracerebral Hodgkin's disease: report of a case with Epstein-Barr virus
      association and review of the literature.
AB  - A case of primary intracerebral Hodgkin's disease (HD) without dural attachment
      in a 54-year-old immunocompetent patient is described. The infiltrate was located
      superficially in the occipital lobe and corresponded to the histologic type of
      nodular sclerosis. A typical immunohistochemical profile (membrane and
      cytoplasmic staining with dotlike Golgi enhancement of CD30, moderate cytoplasmic
      staining of CD15 in the Golgi area, membrane staining of CD20 of <10% of blastic
      cells, CD45RB negative) and in addition Epstein-Barr virus (EBV) latent membrane
      protein was detectable in Reed-Sternberg cells. Staging revealed no other organ
      sites of involvement. After combined surgery, postoperative radiotherapy, and
      chemotherapy, there are no signs of recurrence or systemic disease on follow-up
      for >1 year. To the authors' best knowledge, an association of EBV with primary
      central nervous system HD has not been demonstrated before.

PMID- 10199480
TI  - Epstein-Barr virus-associated intravascular lymphomatosis within Kaposi's sarcoma
      in an AIDS patient.
AB  - Intravascular lymphomatosis (IL) is an unusual neoplasm characterized by
      multifocal proliferation of lymphoma cells exclusively within the blood vessels.
      We report here a patient with acquired immunodeficiency syndrome (AIDS) and
      disseminated Kaposi's sarcoma. A 233-bp amplification product of HHV-8 was
      detected in the DNA extracted from specimens of Kaposi's sarcoma at different
      sites by polymerase chain reaction (PCR). At autopsy, the vessels within the
      Kaposi's sarcoma were dilated and filled with atypical large mononuclear cells.
      No such feature was seen in the vessels of non-Kaposi's sarcomatous regions.
      Immunohistochemically, the spindle cells of Kaposi's sarcoma were positive for
      CD31 (endothelial cell marker). The intravascular tumor cells were positive for
      CD45 (leukocyte common antigen) but negative for others, including chloroacetate
      esterase, CD45-RO (UCHL-1, Pan-T), CD3, CD43, CD20 (L26, Pan-B), CD30 (Ki-1),
      immunoglobulin heavy chains and light chains, CD56 (natural killer cell antigen),
      and CD31. Monoclonal rearrangement of immunoglobulin heavy chain gene was
      detected in the DNA extracts from fresh tissue of Kaposi's sarcoma by PCR, which
      indicated that the lymphoma cells within the Kaposi's sarcoma were of monoclonal
      B cell origin. In situ hybridization revealed that EBER-1 transcripts were
      present in the lymphoma cells of IL but not in the spindle cells of Kaposi's
      sarcoma. To the authors' best knowledge, this is the first instance of IL in an
      AIDS patient with direct evidence of EBV association.

PMID- 10199481
TI  - Fibroepithelial polyps of the anus with epithelial vacuolation.

PMID- 10199482
TI  - Pathogenesis of intraluminal prostatic crystalloids.

PMID- 10199483
TI  - Atypical small acinar proliferations.

PMID- 10199484
TI  - Cytokeratin expression in cauda equina paragangliomas.

PMID- 10199485
TI  - The risks of itinerent anesthesia services.

PMID- 10199486
TI  - Self-reported systemic, immune-mediated disorders in patients with and without
      proplast-teflon implants of the temporomandibular joint.
AB  - PURPOSE: This study investigates the self-reported immune-related health status
      of patients exposed to Proplast-Teflon (P/T) temporomandibular joint (TMJ)
      implants, comparing their health status with a group of patients who were not
      exposed to any alloplastic TMJ implants. It also compares those whose implants
      were removed with those in whom they were retained. PATIENTS AND METHODS:
      Patients seen in a single oral and maxillofacial surgical practice completed a
      detailed self-report questionnaire about physical symptoms and disorders. Sixty
      four had received P/T implants, and 22 were unexposed to any TMJ alloplastic
      implant. Of the P/T-exposed group, 44 had removed and 20 had retained implants.
      RESULTS: In general, P/T-exposed patients did not differ from unexposed patients
      in rates of reported immune-mediated and somatization-related conditions,
      allergies, or symptoms of environmental sensitivity. However, patients with
      removed P/T implants reported significantly more problems in all categories of
      conditions than those with retained P/T implants. This difference was no longer
      statistically significant after controlling for pain severity and sex.
      CONCLUSIONS: Although P/T-exposed patients do not report more systemic health
      conditions than similar patients who were unexposed to alloplastic jaw implants,
      those with removed implants report more conditions and are more likely to be seen
      in clinical practice. This may lead to a bias in the general perception regarding
      the systemic health status of P/T-exposed patients. In addition, effects may be
      secondary to high levels of pain and dysfunction among patients with removed
      implants, rather than implant exposure itself. Future prospective research is
      needed to identify factors associated with implant failure.

PMID- 10199487
TI  - Management of frontal sinus fractures: a review of 33 cases.
AB  - PURPOSE: The purpose of this article is to provide an overview of fracture
      patterns, patient characteristics, and surgical approaches associated with
      frontal sinus fractures. The short- and long-term complications of frontal sinus
      fractures treated over a 20-year period are presented. PATIENTS AND METHODS: The
      records of patients admitted to the University of Kentucky Medical Center from
      1975 through 1994 with a diagnosis of frontal sinus fracture were reviewed.
      Fracture patterns were categorized and information collected related to
      demographics, circumstance of injury, perioperative management, surgical
      procedures, and complications. Long-term complications were studied by asking
      patients to return for clinical and radiographic follow-up. RESULTS: The average
      age of patients with frontal sinus fractures was 32 years. Thirty-one of the 33
      victims were male. Motor vehicle accidents were the most common cause. Twenty-one
      patients had anterior table fractures (type I), 11 had combined
      anterior/posterior table fractures (type II = 9, type IV = 2), and one patient
      had an isolated posterior table fracture (type III). Short-term postoperative and
      perioperative complications were minimal. Long-term complications included acute
      frontal sinusitis (one patient), cosmetic forehead defects (two patients), and
      encephalitis (one patient). CONCLUSIONS: The critical elements to successful
      frontal sinus fracture repair are precise diagnosis of the craniofacial fracture
      pattern, appropriate management of the frontonasal duct(s), and prevention of
      serious brain sequelae. Long-term follow-up of patients with frontal sinus
      injuries is recommended.

PMID- 10199488
TI  - Staged surgical treatment of obstructive sleep apnea syndrome: a review of 35
      patients.
AB  - PURPOSE: The purpose of this study was to investigate the success of a staged
      surgical reconstruction of the upper airway for treatment of obstructive sleep
      apnea syndrome. PATIENTS AND METHODS: Thirty-five patients with obstructive sleep
      apnea syndrome documented by nocturnal polysomnography were treated surgically
      with a staged protocol for reconstruction of the upper airway. All patients were
      evaluated preoperatively by a history and physical examination, including
      fiberoptic nasopharyngoscopy, oropharyngoscopy, and hypopharyngoscopy;
      cephalometric analysis; and laboratory polysomnography. All patients included
      were diagnosed with type II obstruction, with collapse at the oropharyngeal and
      hypopharyngeal levels. Stage I reconstruction consisted of
      uvulopalatopharyngoplasty (UPPP) by the Fujita method and anterior mandibular
      osteotomy (AMO) or inferior sagittal osteotomy (ISO) with genioglossus muscle
      advancement. If stage I was unsuccessful, patients were advanced to stage II and
      stage III, if necessary. Stage II reconstruction consisted of bimaxillary
      advancement with rigid fixation. Stage III reconstruction consisted of hyoid
      myotomy and advancement. RESULTS: All patients underwent follow-up nocturnal
      polysomnography 4 to 6 months after the last surgical procedure. Most patients
      responded positively to stage I reconstruction (respiratory disturbance index
      [RDI] < 20, with O2 saturation 95+%). Twenty-four patients (69%) had
      postoperative RDIs of 20 or less. Of these, 11 patients (31%) had an RDI of five
      or fewer; seven patients (20%) had an RDI between 6 and 10, and six patients
      (17%) had an RDI between 10 and 20. The mean preoperative RDI was 53, and the
      mean postoperative RDI was 19. Of the three patients who elected to proceed to
      stage II reconstruction, all had a postoperative RDI of 10 or less (two patients
      [67%] had an RDI of 5 or less, and one patient [33%] had an RDI of 6 to 10).
      CONCLUSION: This study showed that properly selected patients with obstructive
      sleep apnea syndrome benefit from a staged reconstruction of the upper airway.

PMID- 10199489
TI  - Change in clinical status of third molars in adults during 12 years of
      observation.
AB  - PURPOSE: The aim of the study was to follow the clinical changes in third molar
      status during a 12-year period in patients aged 20 to 32 years. PATIENTS AND
      METHODS: The study was based on a follow-up of 81 university students (32 men, 49
      women). They were clinically examined and panoramic radiographs were taken at
      baseline (mean age, 20.7+/-0.5 years) and at the end of the study (mean age,
      32.6+/-0.6 years). RESULTS: The students had 285 unerupted, partially erupted, or
      fully erupted third molars at the beginning of the study, and 150 at the end. On
      final examination, 115 teeth were erupted. During the first 6 years from age 20
      to 26, various clinical changes took place in the status of the third molars. In
      the second 6 years, until age 32, the two main changes were either removal or
      eruption. During the 12-year follow-up, 22% of third molars erupted, a few even
      after 26 years of age; the percentage of third molars removed was 42%.
      CONCLUSION: Third molars undergo continuous clinical change at least up to the
      age of 32 years.

PMID- 10199490
TI  - Fractures of the condylar process: surgical versus nonsurgical treatment.
AB  - PURPOSE: The purpose of this study was to compare outcomes from surgical and
      nonsurgical treatment of condylar process fractures. PATIENTS AND METHODS: Two
      hundred thirty-four patients with fractures of the mandibular condylar process
      were treated by open or closed methods. In the follow-up study, 150 patients with
      a mean follow-up time of 2.5 years were analyzed using radiologic and objective
      and subjective clinical examinations. RESULTS: No significant difference in
      mobility, joint problems, occlusion, muscle pain, or nerve disorders were
      observed when the surgically and nonsurgically treated patients were compared.
      The only significant difference was in subjective discomfort. Surgically treated
      patients showed significantly more weather sensitivity and pain on maximum mouth
      opening. CONCLUSION: Because of its disadvantages, open surgery is only indicated
      in patients with severely dislocated condylar process fractures.

PMID- 10199491
TI  - The use of maxillary sinus endoscopy in the diagnosis of orbital floor fractures.
AB  - PURPOSE: The goal of the current study was to evaluate the ability to diagnose
      the presence of an inferior orbital wall fracture through the use of a
      transantral endoscopy technique at bedside. PATIENTS AND METHODS: Seven trauma
      patients with initial axial computed tomography (CT) scan findings consistent
      with an orbital floor fracture were studied. Before endoscopy, the patients
      underwent a coronal CT scan with 3-mm cuts for later comparison with the
      endoscopic findings. The surgeon performing the endoscopy procedure was blinded
      to the results of the coronal CT scan. Visual acuity, intraocular pressure, and
      measurement for enophthalmos were performed before endoscopy. The endoscopic
      procedure was performed at the bedside using local anesthesia. A trocar was used
      in the canine fossa to gain access to the maxillary sinus. A 30 degrees and then
      a 70 degrees endoscope were introduced through the trocar to evaluate the
      integrity of the orbital floor (ie, maxillary sinus roof). The degree of mucosal
      injury of the orbital floor and the presence of blood or orbital contents in the
      sinus were recorded. The ophthalmologic examination was repeated after completion
      of endoscopy. RESULTS: The endoscopic procedure was able to be completed in all
      patients. There was no change in the ophthalmologic examination in any patient as
      a result of endoscopy. In six of the seven patients studied, the endoscopic
      findings correlated with the need for surgical intervention to repair the orbital
      floor predicted on the basis of coronal CT scan. This was determined by the
      degree of injury to the orbital floor and the presence of hematoma, exposed bone,
      or fat. In the remaining case, endoscopy was not diagnostic for the presence of a
      fracture because only ecchymosis of the orbital floor was noted. CONCLUSIONS: The
      ability to perform endoscopy under local anesthesia at the bedside is useful in
      those trauma patients whose concomitant injuries may prohibit other diagnostic
      modalities.

PMID- 10199492
TI  - The efficacy of short-term danazol prophylaxis in hereditary angioedema patients
      undergoing maxillofacial and dental procedures.
AB  - PURPOSE: This study evaluated the efficacy of short-term danazol prophylaxis in
      hereditary angioedema patients undergoing maxillofacial or dental procedures.
      PATIENTS AND METHODS: Twelve patients with a history of edema after dental
      procedures were administered danazol (600 mg/d) 4 days preoperatively and 4 days
      postoperatively. The serum levels of complement components were determined
      preoperatively and postoperatively as well as at 6, 12 and 24 hours in six
      patients. RESULTS: None of the 12 patients developed angioneurotic edema. The
      serum levels of the complement components were decreased immediately after
      surgery and returned to normal within 24 hours. CONCLUSION: The short-term
      prophylactic use of danazol in patients with hereditary angioedema undergoing
      oral surgery is an effective preventive measure.

PMID- 10199494
TI  - The in vitro evaluation of a local pedicled osteomyocutaneous mandibular flap for
      the reconstruction of composite mandibular defects.
AB  - PURPOSE: The purpose of this study was to develop and assess the potential
      feasibility of reconstructing composite defects of the mandible with a local
      pedicled osteomyocutaneous mandibular flap. MATERIALS AND METHODS: The flap
      design was established based on anatomic principles. A prospective evaluation of
      the flap was then performed in a fresh cadaver model, and, subsequently, its
      vascular integrity was documented with angiography. RESULTS: The pedicled
      osteomyocutaneous mandibular flap was technically simple to raise and had an
      exceptionally long arc of rotation, which should enable it to fill most compound
      segmental defects of the mandible. Angiographic studies of the harvested flaps
      done under fluoroscopic guidance confirmed that excellent vascularity of all
      components of the flap was present. CONCLUSIONS: The pedicled osteomyocutaneous
      mandibular flap appears to have a sound anatomic basis. Clinical evaluation is
      needed to fully elucidate its potential role in head and neck reconstruction.

PMID- 10199493
TI  - In vitro effects of therapeutic ultrasound on cell proliferation, protein
      synthesis, and cytokine production by human fibroblasts, osteoblasts, and
      monocytes.
AB  - PURPOSE: The aim of this study was to evaluate several in vitro effects of
      ultrasound that could revert or prevent the hypoxia, hypovascularity, and
      hypocellularity observed in osteoradionecrosis. MATERIALS AND METHODS: Two
      different ultrasound machines were evaluated, a "traditional" (1 MHz, pulsed 1:4)
      and a "long wave" (45 kHz, continuous) machine, tested at various intensities.
      Ultrasound was applied to human gingival fibroblasts, mandibular osteoblasts, and
      monocytes. The assays performed were cell proliferation (DNA synthesis), collagen
      and noncollagenous protein (NCP) synthesis, and cytokine production (ELISA)
      involving interleukin (IL) 1 beta, IL-6, and IL-8, tumor necrosis factor alpha
      (TNF alpha), basic fibroblast growth factor (bFGF), and vascular endothelial
      growth factor (VEGF). RESULTS: Both ultrasound machines induced increased cell
      proliferation in fibroblasts and osteoblasts, between 35% and 52%. The collagen
      and NCP synthesis were also significantly enhanced to levels up to 112%, the best
      results being with the 45-kHz machine. The ELISA results showed a slight
      stimulation of IL-1 beta by all cell types; there was no difference in IL-6 and
      TNF alpha levels. The angiogenesis-related cytokines evaluated were significantly
      stimulated: IL-8 and bFGF production was enhanced in osteoblasts, and VEGF
      production was stimulated in all three cell types. Both ultrasound machines
      produced the same results, with the recommended intensities being 15 and 30
      mW/cm2(SA) for the 45-kHz ultrasound, and 0.1 and 0.4 W/cm2(SAPA) for the 1 MHz
      ultrasound. CONCLUSIONS: Therapeutic ultrasound induces in vitro cell
      proliferation, collagen/NCP production, bone formation, and angiogenesis. These
      findings support its use in prospective clinical trials for the prevention and
      treatment of osteoradionecrosis.

PMID- 10199495
TI  - Trigeminal ganglion cell response to mental nerve transection and repair in the
      rat.
AB  - PURPOSE: Animal studies have suggested that peripheral nerve transection results
      in substantial loss of ganglion cells and the selective survival of cells based
      on size. The implications are that subsequent repair of peripheral nerve injuries
      will be determined by the numerical density and character of the surviving cells.
      The purpose of this study was twofold: First, to determine the effect of mental
      nerve transection without repair on trigeminal ganglion cell density and
      morphology in adult rats, and second, to determine the variation of trigeminal
      ganglion cell density and morphology after immediate and delayed repair.
      MATERIALS AND METHODS: In the first part of the study, 12 adult male Sprague
      Dawley rats had their mental nerves exposed bilaterally (n = 24). Twelve mental
      nerves were then transected and prevented from regenerating, and the remaining 12
      nerves were uninjured. Ninety and 180 days after transection or sham surgery, the
      trigeminal ganglia were serially cut into 5 microm longitudinal sections along
      the dorsoventral axis. The volume and volume density of the mandibular mental
      subdivision containing sensory cells was determined at each section level with
      point-counting methods. The numerical density and total number of cells was
      estimated on the same section, using an unbiased three-dimensional stereological
      probe, the dissector. Cell size and shape determinants were estimated using the
      dissector and computerized planimetry. In the second part of the study, six rats
      had the mental nerves transected bilaterally and immediately repaired by
      microscopic sutures. In six additional rats, the repair was delayed for 90 days.
      In both groups, the trigeminal ganglia were serially cut at 30, 60, and 90 days
      post-repair and stereologic estimates of numerical density and histomorphometry
      were examined using the dissector and computed planimetry. RESULTS: In the
      trigeminal ganglia of the 12 sham-operated animals, the mean number of cells was
      20.6 x 10(3) (+/-2.9 X 10(3)). After nerve section, the mean number of cells was
      10.88 X 10(3) (+/-0.9 X 10(3)), representing a 47% reduction. The mean volume of
      the mandibular subdivision cells in the ganglia of the sham surgery animals was
      0.3 mm3 (+/-0.05) and 0.22 mm3 (+/-0.04) in nerve-sectioned ganglia, a 38%
      difference. There were no ganglia cell size or shape differences between the two
      groups. The mean number of cells in the ganglia of immediately repaired nerves
      was 10.66 x 10(3)(+/-1.1 X 10(3)), and it was 12.45 x 10(3) (+/-0.9 x 10(3))
      after delayed repair. The numerical density was significantly less than in the
      sham surgery ganglia but not different from that of the transection/no repair
      ganglia. The weighted mean reference volume of the mandibular subdivision after
      immediate and delayed repair was similar and was significantly greater than the
      transection/no repair group, but not different from the sham surgery group. The
      cell size was slightly larger in delayed-repair ganglia compared with immediate
      repair ganglia, but the differences were not significant. There were no
      significant differences in any of the stereologic estimates when analyzed across
      treatment time. CONCLUSIONS: The results of this study agree with previous
      reports that peripheral nerve transection produces a substantial loss of nerve
      cells within specified regions of sensory ganglions. However, the results
      conflict with evidence that cells survive transection based on size and shape.
      These findings also indicate that in the adult rat the substantial loss of nerve
      cells was unaltered by the reconnection of their severed axons. Neither immediate
      or delayed repair of the transected nerve altered the spectrum of surviving cells
      based on size or shape. The reestablishment of the mean reference volume of the
      mandibular subdivision after section and repair suggests that demands made on
      regenerating axons appear to result in the restoration of ganglionic volume
      normally lost after axotomy, probably the result of axo

PMID- 10199496
TI  - The third molar controversy: framing the controversy as a public health policy
      issue.
AB  - PURPOSE: This article summarizes the current research available concerning the
      removal of impacted third molars, and provides a background from which
      practitioners, public health policy advocates, and third-party payers can more
      objectively assess the the issues of appropriateness of care and overutilization
      of third molar surgery. MATERIALS AND METHODS: A literature review was
      undertaken, with emphasis on noninterventional outcome studies and studies using
      statistical modeling techniques. RESULTS: The health care resources being devoted
      to the removal of third molars are in the billions of dollars. There is an
      attempt at limiting these expenditures by third-party payers. These attempts have
      focused on the prophylactic removal of asymptomatic third molars. Some sources
      label the procedure as unnecessary surgery. Analysis of the literature does not
      answer this question with any degree of confidence. CONCLUSION: There appears to
      be a need for large population-based studies to provide practitioners with data
      to help them decide when intervention is indicated and when it is not. There is
      little agreement on how many third molars are being removed for so-called
      prophylactic reasons. The studies that are available on the nonintervention
      course are few and have significant flaws. The studies that argue against
      prophylactic removal are largely based on statistical models. The application of
      these models as a basis for clinical decision making is questionable. The effects
      of provider supply and reimbursement must be considered as an integral part of
      the controversy.

PMID- 10199497
TI  - Infiltrating angiolipoma of the mucolabial fold: a case report and review of the
      literature.

PMID- 10199499
TI  - Myositis ossificans traumatica of the medial pterygoid muscle.

PMID- 10199498
TI  - Solitary mucosal "infantile" myofibroma in a 21-year-old man.

PMID- 10199500
TI  - Reconstruction of the temporomandibular joint using calvarial bone after a failed
      Teflon-Proplast implant.

PMID- 10199501
TI  - Glandular odontogenic cyst of the mandible.

PMID- 10199502
TI  - Hypertrophic branchial myopathy with uniform type 2 fibers: a case report.

PMID- 10199503
TI  - Securing a genioplasty segment with a fixed mandibular implant.

PMID- 10199504
TI  - Posterior vertical body osteotomy (PVBO): a predictable rescue procedure for
      proximal segment fracture during sagittal split ramus osteotomy of the mandible.

PMID- 10199505
TI  - A case of a new entity named unilateral dysplasia of the mandibular condyle.

PMID- 10199506
TI  - Blood pressure and intracerebral hemorrhage.

PMID- 10199507
TI  - An appreciation of cardiac resuscitation.

PMID- 10199508
TI  - Multiple mechanisms of excitotoxicity.

PMID- 10199509
TI  - Acute phase proteins and the systemic inflammatory response.

PMID- 10199510
TI  - Subarachnoid hemorrhage, systemic immune response syndrome, and MODS: is there
      cross-talk between the injured brain and the extra-cerebral organ systems?
      Multiple organ dysfunction syndrome.

PMID- 10199511
TI  - Unfinished business: assessing the efficacy of extraluminal silver ions on the
      prevention of microbial colonization and catheter-associated infection.

PMID- 10199512
TI  - Psychiatric treatment helps survivors of suicide attempts.

PMID- 10199513
TI  - Effects of ventilator resetting on indirect calorimetry measurement--the
      importance of patience.

PMID- 10199514
TI  - Volume loading for acute circulatory failure from pulmonary embolism.

PMID- 10199515
TI  - No steroids or STITCH for CPB?

PMID- 10199516
TI  - Early diagnosis of septic shock: a simple test for a complex condition?

PMID- 10199517
TI  - Dobutamine: empirical generalizations vs. age appropriate evidence.

PMID- 10199518
TI  - The unorthodox and orthodox: the therapeutic role of acadesine after traumatic
      injury and sepsis.

PMID- 10199519
TI  - Searching for the perfect indicator of dysoxia.

PMID- 10199520
TI  - Pleural effusions and hypoxemia.

PMID- 10199521
TI  - Hemofiltration and left ventricular function in sepsis: mechanisms and clinical
      implications.

PMID- 10199522
TI  - Between a rock and a hard place: myocardial ischemia in the worst of times.

PMID- 10199523
TI  - Intracranial hemorrhage: time for an intervention.

PMID- 10199524
TI  - Cerebral perfusion in cerebral malaria.

PMID- 10199525
TI  - Rate of 24-hour blood pressure decline and mortality after spontaneous
      intracerebral hemorrhage: a retrospective analysis with a random effects
      regression model.
AB  - OBJECTIVE: To study the effect of decline in blood pressure on mortality in
      patients with spontaneous intracerebral hemorrhage (ICH). DESIGN: Retrospective
      chart review. SETTING: University-affiliated teaching hospital. PATIENTS:
      Consecutive patients admitted with spontaneous ICH over a 3-year period.
      MEASURES: Blood pressure recordings were obtained from the first 24 hrs. Patients
      (n = 105) with more than five blood pressure recordings and on average greater
      than one measurement per 2 hrs were included (mean measurements per patient =
      20.3). Mean arterial pressure (MAP) recordings over the first 24 hrs after
      presentation were regressed on time for each patient. Each patient's MAP was
      calculated as a slope (change mm Hg/hr). We performed logistic regression
      analyses to determine the effect of MAP slope on mortality and functional
      outcome, adjusting for other predictive factors including Glasgow Coma Scale
      (GCS) score and hematoma volume. The effect of MAP slope on mortality was also
      evaluated in subsets of patients based on age, gender, initial GCS score, initial
      MAP, treatment status, hematoma volume, and presence of ventricular blood. MAIN
      RESULTS: Mean slope of change in MAP was -2.0 mm Hg/hr (+/- 1.9, range -8.5 to
      +0.6). The slope of MAP (faster rate of decline) within the first 24 hrs was
      significantly associated with higher mortality (p =.04), independent of initial
      GCS score and hematoma volume. In subgroup analyses, MAP slope was significantly
      associated with mortality in men (p = .08), patients with hematoma volume <50 mm3
      (p =.08), initial MAP < or = 146 mm Hg (p = .006), and those with initial GCS
      score > or = 10 (p= .07). MAP slope did not predict functional outcome among
      survivors. CONCLUSIONS: A rapid decline in MAP within 24 hrs after presentation
      is independently associated with increased mortality in patients with ICH. A
      large, prospective, randomized trial is required to confirm these findings.

PMID- 10199526
TI  - Vasopressin improves vital organ blood flow after prolonged cardiac arrest with
      postcountershock pulseless electrical activity in pigs.
AB  - OBJECTIVE: Although a benefit of vasopressin when compared with epinephrine was
      shown during cardiopulmonary resuscitation (CPR) after a short duration of
      ventricular fibrillation cardiac arrest, the effect of vasopressin during
      prolonged cardiac arrest with pulseless electrical activity is currently unknown.
      DESIGN: Prospective, randomized laboratory investigation using an established
      porcine model with instrumentation for measurement of hemodynamic variables,
      vital organ blood flow, blood gases, and return of spontaneous circulation.
      SETTING: University hospital laboratory. SUBJECTS: Eighteen domestic pigs.
      INTERVENTIONS: After 15 mins of cardiac arrest and 3 mins of chest compressions,
      18 animals were randomly treated with either 0.8 units/kg vasopressin (n = 9) or
      200 microg/kg epinephrine (n = 9). MEASUREMENTS AND MAIN RESULTS: Compared with
      epinephrine, vasopressin resulted, at both 90 secs and 5 mins after drug
      administration, in significantly higher (p < .05) median (25th-75th percentiles)
      left ventricular myocardial blood flow (120 [range, 96-193] vs. 54 [range, 11-92]
      and 56 [range, 41-80] vs. 21 [range, 11-40] mL/min/100 g, respectively) and total
      cerebral blood flow (85 [78-102] vs. 24 [18-41] and 50 [44-52] vs. 8 [5-23]
      mL/min/100 g, respectively). Spontaneous circulation was restored in eight of
      nine animals in the vasopressin group and in one of nine animals in the
      epinephrine group (p = .003). CONCLUSIONS: Compared with a maximum dose of
      epinephrine, vasopressin significantly increased left ventricular myocardial and
      total cerebral blood flow during CPR and return of spontaneous circulation in a
      porcine model of prolonged cardiac arrest with postcountershock pulseless
      electrical activity.

PMID- 10199527
TI  - Quinolinic acid in the cerebrospinal fluid of children after traumatic brain
      injury.
AB  - OBJECTIVE: To measure quinolinic acid, a macrophage-derived neurotoxin, in the
      cerebrospinal fluid (CSF) of children after traumatic brain injury (TBI) and to
      correlate CSF quinolinic acid concentrations to clinically important variables.
      DESIGN: A prospective, observational study. SETTING: The pediatric intensive care
      unit in Children's Hospital of Pittsburgh, a tertiary care, university-based
      children's hospital. PATIENTS: Seventeen critically ill children following severe
      TBI (Glasgow Coma Scale score <8) whose care required the placement of an
      intraventricular catheter for continuous drainage of CSF. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Patients ranged in age from 2 mos to 16 yrs (mean
      6.0 yrs). CSF was collected immediately on placement of the ventricular catheter
      and daily thereafter. Quinolinic acid concentration was measured by gas
      chromatography/mass spectroscopy in 69 samples (4.0 +/- 0.4 [SEM] samples per
      patient). CSF quinolinic acid concentration progressively increased after injury
      (p = .034, multivariate analysis) and was increased in nonsurvivors vs. survivors
      (p = .002, multivariate analysis). CSF quinolinic acid concentration was not
      associated with age. Although overall CSF quinolinic acid concentration was not
      associated with shaken injury (p = .16, multivariate analysis), infants suffering
      with shaken infant syndrome had increased admission CSF quinolinic acid
      concentrations compared with children with accidental mechanisms of injury (p =
      .027, Mann-Whitney Rank Sum test). CONCLUSIONS: A large and progressive increase
      in the macrophage-derived neurotoxin quinolinic acid is seen following severe TBI
      in children. The increase is strongly associated with increased mortality.
      Increased CSF quinolinic acid concentration on admission in children with shaken
      infant syndrome could reflect a delay in presentation to medical attention or age
      related differences in quinolinic acid production. These findings raise the
      possibility that quinolinic acid may play a role in secondary injury after TBI in
      children and suggest an interaction between inflammatory and excitotoxic
      mechanisms of injury following TBI.

PMID- 10199528
TI  - Procalcitonin used as a marker of infection in the intensive care unit.
AB  - OBJECTIVE: To determine the value of procalcitonin (ProCT) as a marker of
      infection in critically ill patients. DESIGN: Prospective, observational study.
      SETTING: Medicosurgical department of intensive care (31 beds). PATIENTS: One
      hundred eleven infected and 79 noninfected patients. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: ProCT and C-reactive protein (CRP) concentrations
      were monitored daily. The best cutoff values for ProCT and CRP were 0.6 ng/mL and
      7.9 mg/dL, respectively. Compared with CRP, ProCT had a lower sensitivity (67.6
      vs. 71.8), specificity (61.3 vs. 66.6), and area under the receiver operating
      characteristic curve (0.66 vs. 0.78, p < .05). The combination of ProCT and CRP
      increased the specificity for infection to 82.3%. In the infected patients,
      plasma ProCT, but not CRP, values were higher in nonsurvivors than in survivors.
      Infected patients with bacteremia had higher ProCT concentrations than those
      without bacteremia, but similar CRP concentrations. ProCT levels were
      particularly high in septic shock patients. CONCLUSIONS: ProCT is not a better
      marker of infection than CRP in critically ill patients, but it can represent a
      useful adjunctive parameter to identify infection and is a useful marker of the
      severity of infection.

PMID- 10199529
TI  - Extracerebral organ dysfunction and neurologic outcome after aneurysmal
      subarachnoid hemorrhage.
AB  - OBJECTIVE: To analyze the influence of extracerebral organ system dysfunction
      after aneurysmal subarachnoid hemorrhage (SAH) on mortality and neurologic
      outcome. DESIGN: Observational study with retrospective data extraction. SETTING:
      Neurosurgical intensive care unit (NICU) at a primary level university hospital,
      supervised and staffed by both members of the Clinic of Neurosurgery and the
      Clinic of Anesthesiology and General Intensive Care. PATIENTS: Two hundred forty
      two patients treated for intracranial aneurysm rupture within 7 days of the most
      recent SAH. INTERVENTIONS: Routine neurosurgical interventions for obliteration
      of the ruptured aneurysm (microsurgery, Guglielmi Detachable Coils embolization)
      and for treatment of posthemorrhagic hydrocephalus (ventriculostomy,
      cerebrospinal fluid shunt implantation). MEASUREMENTS AND MAIN RESULTS:
      Respiratory, renal, hepatic, cardiovascular, and hematologic organ system
      functions were evaluated both individually and in aggregate by using a modified
      version of the Multiple Organ Dysfunction (mMOD) score. Of 1,452 organ system
      functions assessed in 242 patients during their NICU stay, 714 organ system
      functions were intact (cerebral: 0, extracerebral: 714), 556 organ systems had
      mild-to-moderate dysfunctions (mMOD scoremax 1-2 for the affected organ system;
      cerebral: 153, extracerebral: 403), and 182 organ systems failed (mMOD scoremax 3
      for the affected organ system; cerebral: 89, extracerebral: 93). Severity of
      extracerebral organ system dysfunctions correlated with the degree of neurologic
      impairment (Hunt and Hess [H&H] score) in a graded fashion. Similarly, the chance
      to develop systemic inflammatory response syndrome (SIRS) during the NICU stay
      increased with increasing admission H&H grade. The incidence of SIRS and septic
      shock was 29% and 10.3%, respectively. The mortality rate was 40.2% in patients
      with SIRS and 80% for patients suffering septic shock. Seventy-seven percent of
      extracerebral organ system failures (OSFs) occurred in conjunction with SIRS: 51%
      of respiratory OSFs, 97% of renal OSFs, 100% of hepatic OSFs, 96% of
      cardiovascular OSFs, and 73% of hematopoietic OSFs. Both CNS dysfunction and
      extracerebral organ system dysfunctions were significantly related to neurologic
      outcome. The probability of unfavorable neurologic outcome significantly
      increased with both decreasing cerebral perfusion pressure (CPP) and increasing
      severity of extracerebral organ dysfunction. CONCLUSION: Aneurysmal SAH and its
      neurologic sequelae accounted for the principal morbidity and mortality in the
      current series. Development of extracerebral organ system dysfunction was
      associated with a higher probability of unfavorable neurologic outcome. Systemic
      inflammation (SIRS) and secondary organ dysfunction were the principal non
      neurologic causes of death.

PMID- 10199530
TI  - Efficacy of silver-coating central venous catheters in reducing bacterial
      colonization.
AB  - OBJECTIVE: To compare silver-coated and uncoated central venous catheters
      regarding bacterial colonization. To assess the relative contribution of catheter
      hub and skin colonization to catheter tip colonization. DESIGN: Prospective,
      randomized clinical trial. SETTING: Intensive care unit in a university hospital.
      PATIENTS: Patients after cardiac surgery who required a central venous double
      lumen catheter (DLC). INTERVENTIONS: Sixty-seven adult patients were
      prospectively randomized to receive either a silver-coated (S group, n = 34) or
      an uncoated control (C group, n = 33) DLC. Blood cultures were drawn at catheter
      removal, and removed catheters were analyzed with quantitative cultures. Typing
      of microorganisms included DNA fingerprinting. MEASUREMENTS AND MAIN RESULTS:
      Catheters were removed if no longer necessary and aseptically divided into three
      segments: segment A, the catheter tip; segment B, an intermediate section; and
      segment C, the subcutaneous portion. Bacterial catheter colonization was
      quantitatively measured using sonication to detach adherent bacteria from the
      catheter segments in the broth and subsequent culture of an aliquot. Selected
      isolates of coagulase-negative staphylococci and other bacteria from catheter
      segments were examined by means of pulsed-field gel electrophoresis (PFGE) after
      macrorestriction digestion of bacterial DNA to study colonization pathogenesis.
      Quantitatively lower bacterial colonization could be demonstrated on the silver
      coated catheters (200 +/- 550 colony forming units [CFUs]/cm catheter segment;
      mean +/- SD). The difference in the control catheters (1120 +/- 5350 CFUs/cm
      catheter segment; mean +/- SD) was not, however, significant (p = .25). The
      frequency of colonization of at least one catheter segment was 52.9% for the
      silver-coated catheters and 57.6% for the control catheters (p= .44), without any
      significant differences in the colonization of corresponding catheter segments.
      The rate of significant catheter colonization (i.e., > or = 10(3) CFUs/cm
      catheter by quantitative catheter culture or > or = 10(3) CFUs/mL by luminal
      flush) was nine in the silver group and seven in the control group, a difference
      that failed to reach significance (p = .41). Two patients in both groups
      developed catheter-related bacteremia. Pattern analysis after PFGE demonstrated
      that about 70% of the isolates found on the catheter tip were identical with
      those on the skin at the insertion site, whereas about 75% were identical with
      those recovered from the hub. In 29% of colonized catheters, identical bacteria
      were found on the hub and the skin at the insertion site. CONCLUSIONS: Silver
      coating of DLCs did not significantly reduce bacterial catheter colonization
      compared with the control catheters. PFGE analysis of coagulase-negative
      staphylococci and other bacteria demonstrated various pathogenic routes of
      catheter-related colonization, whereby the microorganisms of the skin flora
      around the insertion site must be regarded as the main source of catheter-related
      infections.

PMID- 10199531
TI  - Long-term results and quality of life after parasuicidal multiple blunt trauma.
AB  - OBJECTIVE: This study evaluates the somatic, socioeconomic, and psychiatric long
      term results, as well as the factors for adverse outcome, in a significant subset
      of patients with severe multiple injuries resulting from attempted suicide.
      DESIGN: The follow-up study 6.1 +/- 3 (SD) yrs after trauma was based on
      prospectively documented data of patients with multiple injuries. SETTING: Level
      I university trauma center in a major German city. MEASUREMENTS AND MAIN RESULTS:
      Data derived from thorough physical and psychiatric evaluations. The Brief
      Psychiatric Rating Scale and the Global Assessment of Functioning Scale served to
      describe psychiatric outcome. PATIENTS: In a series of 539 severely injured
      patients (Abbreviated Injury Score in two regions > or = 3), 65 (12%) attempted
      suicides were reported (Injury Severity Score, 40 +/- 15; age, 38 +/- 18 yrs).
      Twenty-one patients of the study cohort died during the hospital stay, and six
      subjects died thereafter, none because of suicide. Three patients were lost to
      follow-up, resulting in 35 individuals eligible for examination. None of the
      latter had reattempted suicide. Seventeen (48%) had good or satisfactory outcomes
      reflected by absent or ambulatory psychiatric treatment, employment, normal
      psychiatric findings (Brief Psychiatric Rating Scale), and good psychosocial
      ability (Global Assessment of Functioning Scale). For eight patients (24%), the
      result was indeterminate. The adverse outcomes in ten patients (28%) were mainly
      influenced by the presence of chronic schizophrenia (n = 4), affective disorder
      (n = 2), or severe traumatic brain injury (n = 3). CONCLUSIONS: Despite the
      parasuicidal origin, the long-term results after severe trauma were good or
      satisfactory in approximately half the cases and without further suicide attempts
      in any of the patients. Good recovery of the parasuicidal patients in our study
      is approximately 20% lower than in an unselected group of patients with multiple
      injuries and may be attributed mainly to the underlying chronic psychiatric
      disease.

PMID- 10199532
TI  - Effects of ventilator resetting on indirect calorimetry measurement in the
      critically ill surgical patient.
AB  - OBJECTIVE: To evaluate the effect of acute changes in minute ventilation (VE) on
      oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory quotient,
      and energy expenditure during volume-controlled mechanical ventilation in the
      critically ill surgical patient. The effects on some oxygen transport variables
      were assessed as well. DESIGN: Prospective, randomized clinical study SETTING:
      Adult surgical intensive care unit of a university teaching hospital. PATIENTS:
      Twenty adult critically ill surgical patients were studied during volume
      controlled mechanical ventilation. INTERVENTIONS: After a basal period of
      stability (no changes over time in body temperature, energy expenditure, blood
      gases, acid-base status, cardiac output, and ventilatory parameters), VE was then
      randomly either increased or reduced (+/-35%) by a change in tidal volume (VT),
      while respiratory rate and inspiratory/expiratory ratio were kept constant.
      Settings were then maintained for 120 mins. During the study, patients were
      sedated and paralyzed. MEASUREMENTS AND MAIN RESULTS: VO2, VCO2, and respiratory
      quotient were measured continuously by a Nellcor Puritan Bennett 7250 metabolic
      monitor (Nellcor Puritan Bennett, Carlsbad, CA). Hemodynamic and oxygen transport
      parameters were obtained every 15 mins during the study. Despite large changes in
      VE, VO2 and energy expenditure did not change significantly either in the
      increased or in the reduced VE groups. After 15 mins, VCO2 and respiratory
      quotient changed significantly after ventilator resetting. VCO2 increased by 10.5
      +/- 1.1% (from 2.5 +/- 0.10 to 2.8 +/- 0.12 mL/min/kg, p< .01) in the increased
      VE group and decreased by 12.4 +/- 2.1% (from 2.7 +/- 0.17 to 2.4 +/- 0.16
      mL/min/kg, p< .01) in the reduced VE group. Similarly, respiratory quotient
      increased by 16.2% +/- 2.2% (from 0.87 +/- 0.02 to 1.02 +/- 0.02, p< .01) and
      decreased by 17.2% +/- 1.8% (from 0.88 +/- 0.02 to 0.73 +/- 0.02, p< .01). VCO2
      normalized in the reduced VE group, but remained higher than baseline in the
      increased VE group. Respiratory quotient did not normalize in both groups and
      remained significantly different from baseline at the end of the study. Cardiac
      index, oxygen delivery, and mixed venous oxygen saturation increased, while
      oxygen extraction index decreased significantly in the reduced VE group. Neither
      of the mentioned parameters changed significantly in the increased VE group.
      CONCLUSIONS: We conclude that, during controlled mechanical ventilation, the time
      course and the magnitude of the effect on gas exchange and energy expenditure
      measurements caused by acute changes in VE suggest that VO2 and energy
      expenditure measurements can be used reliably to evaluate and quantify metabolic
      events and that VCO2 and respiratory quotient measurements are useless for
      metabolic purposes at least for 120 mins after ventilator resetting.

PMID- 10199533
TI  - Hemodynamic effects of fluid loading in acute massive pulmonary embolism.
AB  - OBJECTIVE: To assess the hemodynamic effects of fluid loading in patients with
      acute circulatory failure caused by acute massive pulmonary embolism (AMPE).
      DESIGN: Prospective study. SETTING: Respiratory critical care unit of a
      university hospital. PATIENTS: Thirteen patients free of previous cardiopulmonary
      disease with angiographically proven AMPE (Miller index = 24 +/- 1), with acute
      circulatory failure defined by a cardiac index (CI) lower than 2.5 L/min/m2.
      INTERVENTION: Infusion of 500 mL of dextran 40 over 20 mins. MEASUREMENTS AND
      MAIN RESULTS: Fluid loading induced a substantial increase in right atrial
      pressure from 9 +/- 1 mm Hg to 17 +/- 1 mm Hg and in right ventricular end
      diastolic volume index from 123 +/- 14 mL/m2 to 150 +/- 11 mL/m2 (p < .05 for
      both comparisons). The increase in right ventricular preload was associated with
      an increase in Cl from 1.6 +/- 0.1 to 2.0 +/- 0.1 L/min/m2 (p < .05), whereas
      right ventricular ejection fraction (15 +/- 3% at baseline vs. 16 +/- 3% after
      fluid loading) and total pulmonary vascular resistance index (1689 +/- 187 dyne x
      sec/cm5 x m2 at baseline vs. 1492 +/- 166 dyne x sec/ cm5 x m2 after fluid
      loading) remained unchanged. The increase in Cl induced by fluid loading was
      inversely correlated to baseline right ventricular end-diastolic volume index (r
      = -.89 ; p< .05). CONCLUSIONS: These results suggest that fluid loading can
      improve hemodynamic status in patients with acute circulatory failure caused by
      AMPE.

PMID- 10199534
TI  - Influence of methylprednisolone on cytokine balance during cardiac surgery.
AB  - OBJECTIVE: To determine the influence of methylprednisolone on the cytokine
      balance during cardiac surgery. DESIGN: Prospective, randomized, nonblinded
      study. SETTING: University hospital. PATIENTS: Twenty-one patients on
      cardiopulmonary bypass undergoing aortocoronary bypass surgery. INTERVENTIONS:
      According to a randomized sequence, the patients either received
      methylprednisolone (30 mg/kg) [corrected] before cardiopulmonary bypass and
      before declamping of the aorta (MPS group, n = 11) or received nothing (control
      group, n = 10). MEASUREMENTS AND MAIN RESULTS: Serum proinflammatory cytokines
      (interleukin [IL]-8, IL-6) and anti-inflammatory cytokines (IL-10, IL-1ra) were
      measured by enzyme-linked immunosorbent assays. Serum IL-6 and IL-8
      concentrations in the control group (15.2 +/- 4.1 and 14.1 +/- 1.9 pg/mL,
      preoperatively) increased to 242 +/- 70.1 and 97.3 +/- 18.3 pg/mL at 60 mins
      after declamping of the aorta (p < .01, p < .01, respectively). The increases
      were greater than those from 2.5 +/- 0.6 and 2.5 +/- 0.5 pg/mL to 109.5 +/- 29.0
      and 33 +/- 4.1 pg/mL in the MPS group for IL-6 and IL-8, respectively. Serum IL
      10 concentrations increased significantly 60 mins after declamping of the aorta
      compared with its preoperative value in the two groups (the control group, from
      1.0 +/- 0 to 537.9 +/- 61.7 pg/mL; the MPS group, from 0.3 +/- 0.2 to 654.9 +/-
      24 pg/mL [p < .01, p < .01, respectively]). No difference was found between the
      two groups. Similarly, serum IL-1ra concentrations in the two groups increased
      the preoperative value in the control group from 304 +/- 120 to 44,374 +/- 14,631
      pg/mL and in the MPS group from 616.5 +/- 109.6 to 35,598 +/- 9,074 pg/mL at 60
      mins after declamping of the aorta (p < .01, p < .01, respectively). There was no
      difference between the two groups. CONCLUSIONS: Methylprednisolone reduces the
      production of IL-6 and IL-8 but not that of IL-10 and IL-1ra. These results
      suggest that one of the mechanisms of the cytoprotective effect of
      methylprednisolone may be to make changes in the proinflammatory and anti
      inflammatory cytokine balance.

PMID- 10199535
TI  - Neutrophil function capacity to express CD10 is decreased in patients with septic
      shock.
AB  - OBJECTIVE: To evaluate the performance of a newly developed assay to assess
      neutrophil function capacity. After optimization, the assay was performed on
      samples derived from patients with septic shock and compared with healthy
      controls and patients with a systemic viral infection. DESIGN: Prospective
      evaluation of the performance of a new assay. SETTINGS: Medical intensive care
      unit, hospital laboratory. PATIENTS: Ten patients with septic shock, ten patients
      with infectious mononucleosis, and ten healthy controls. MEASUREMENTS AND MAIN
      RESULTS: We report an assay to assess neutrophil function capacity, in which CD10
      membrane expression is measured by FACS before and after in vitro stimulation
      with Staphylococcus aureus bacteria. This assay evaluates the early activation
      state of circulating neutrophils and is shown to be of value in diagnosing a
      sepsis syndrome. First the assay was optimized. As an anticoagulant, sodium
      citrate gave the best results. Blood samples must be kept on ice to reduce
      activation inside the siliconized tube and can be stored in this way for at least
      8 hrs without affecting the test results. Kinetic studies showed a maximal
      expression of CD10 on neutrophils of healthy volunteers after 15 mins of
      stimulation with S. aureus bacteria. Second, the test was performed on samples
      derived from ten septic patients and ten patients with infectious mononucleosis.
      Septic patients had a significantly decreased CD10 expression capacity compared
      with healthy controls. Patients with infectious mononucleosis have a
      significantly higher CD10 expression capacity compared with septic patients, but
      in approximately one-half of them, the expression capacity was below the range
      found in controls. CONCLUSIONS: These results indicate that in circulating
      neutrophils, the secretory vesicles have been mobilized completely in patients
      with septic shock. The assay proves to be of acceptable analytical quality and
      can be quickly and easily performed. Regarding clinical performance, this assay
      may be helpful in diagnosing septic shock.

PMID- 10199536
TI  - Systemic inflammatory response syndrome in patients hospitalized for
      gastrointestinal bleeding.
AB  - OBJECTIVE: To describe the incidence and causes of systemic inflammatory response
      syndrome (SIRS), to determine the risk factors for its development, and to assess
      its impact on the outcome of patients hospitalized for gastrointestinal bleeding.
      DESIGN: Prospective, observational study. SETTING: A 528-bed, university
      affiliated, teaching hospital. PATIENTS: The study included 411 adults
      hospitalized for gastrointestinal bleeding from January 1, 1995, through June 30,
      1996. MEASUREMENTS: We obtained the demographic data, selected clinical findings,
      laboratory values, length of hospital stay, presence and cause of SIRS, presence
      of organ failure, and in-hospital mortality for each patient. The Acute
      Physiology and Chronic Health Evaluation II (APACHE II) score was calculated.
      Univariate and multivariate logistic regression analyses were used to determine
      differences between groups. RESULTS: Patients' ages (mean +/- SD) were 55.9 +/-
      17.3 yr; 227 (55%) were male; 247 (60%) were African-American. SIRS developed in
      112 patients (27%). Sepsis was the cause of SIRS in 63% of patients (70/112).
      Severe sepsis developed in 20 patients and septic shock in 5 patients. The most
      common cause of sepsis was pneumonia (19). There were no significant differences
      in age, gender, race, and the presence of liver disease between patients with and
      without SIRS. Upper gastrointestinal bleeding (76/211 vs. 36/ 200; p = .0196),
      intensive care unit admission (73/152 vs. 391259; p < .0001), and higher APACHE
      II scores (median, 17 vs. 11; p< .0001) were associated with the development of
      SIRS. The length of hospital stay was longer (median, 9.5 vs. 3 days; p < .0001),
      and the number of organ failures (median, 1 vs. 0; p < .0001) and in-hospital
      mortality rates (23 vs. 4%; p < .0001) were higher in patients with SIRS than in
      those without SIRS. CONCLUSIONS: SIRS occurs in 27% of patients admitted for
      gastrointestinal bleeding and is associated with a poor prognosis. Intensive care
      unit admission, upper gastrointestinal bleeding, and high APACHE II scores are
      risk factors for the development of SIRS in patients hospitalized for
      gastrointestinal bleeding.

PMID- 10199537
TI  - The hemodynamic effects of dobutamine infusion in the chronically instrumented
      newborn piglet.
AB  - OBJECTIVE: To determine the systemic, pulmonary, mesenteric, and renal
      hemodynamic effects of short and prolonged infusions of dobutamine. DESIGN:
      Prospective randomized unblinded study. SETTING: University research laboratory.
      SUBJECTS: Thirteen newborn (1-3 days old) piglets. INTERVENTIONS: Piglets were
      instrumented and studied 48 hrs later. Fifteen-minute infusions of dobutamine at
      5, 10, 20 and 50 microg/ kg x min were randomly given with 15-min rests between
      the doses. After a 1-hr hiatus, a dose of 10 microg/kg x min was continuously
      administered for 2 hrs. MEASUREMENTS AND MAIN RESULTS: Systemic and pulmonary
      arterial pressures, cardiac index (thermodilution), and superior mesenteric and
      renal artery flows were measured. Vascular resistance values were calculated.
      MAIN RESULTS: Fifteen-minute infusions: Dobutamine dose-dependently increased
      cardiac index with tachycardia but not stroke volume (from 187 +/- 43 to 238 +/-
      51 mL/kg x min at baseline and 50 microg/ kg x min, respectively, p < .05; values
      expressed as mean +/- SD). Systemic, but not pulmonary, vascular resistance
      decreased, resulting in a significant decrease in systemic to pulmonary arterial
      pressure ratio (from 3.8 +/- 0.8 at baseline to 3.2 +/- 1.0 at 50 microg/ kg x
      min). Superior mesenteric and renal flows were not affected. Two-hour infusion at
      10 microg/kg x min: Cardiac index progressively increased from 173 +/- 34 to 240
      +/- 58 mL/kg x min at baseline and 120 mins, respectively, (p < .05). The initial
      tachycardia was transient, and stroke volume was significantly increased at 60
      mins and thereafter. Although systemic and pulmonary vascular resistance values
      fell simultaneously, systemic to pulmonary arterial pressure ratio decreased
      significantly to 3.4 +/- 0.9 at 120 mins from 3.9 +/- 0.7 at baseline. Superior
      mesenteric and renal artery flows increased significantly with vasodilation after
      60 mins. CONCLUSIONS: Short infusions of dobutamine dose-dependently increase
      cardiac output due to tachycardia, without significant effect on mesenteric and
      renal blood flows. Prolonged infusion of dobutamine at 10 microg/kg x min
      progressively increases cardiac output and stroke volume with transient
      tachycardia, and increases mesenteric and renal blood flows. Caution is required
      in the treatment of critically ill neonates with dobutamine, which could also
      reduce systemic to pulmonary arterial pressure ratio.

PMID- 10199538
TI  - Acadesine during fluid resuscitation from shock and abdominal sepsis.
AB  - OBJECTIVE: To determine properties of acadesine, the prototype adenosine
      regulating agent, in an experimental model in which abdominal sepsis is
      superimposed onto hemorrhagic shock. DESIGN: Randomized, blinded animal study.
      SETTING: University-based animal research facility. SUBJECTS: Twenty-eight
      anesthetized mongrel pigs (35.5 +/- 1.1 kg). INTERVENTIONS: The cecum was ligated
      and punctured to produce abdominal sepsis. To produce hemorrhagic shock, 45% to
      47% of the estimated blood volume was withdrawn. After 1 hr, shed blood plus
      supplemental crystalloid (twice the shed blood volume) plus either acadesine (5
      mg/kg bolus + 1 mg/kg x 60 min, n = 10) or its vehicle (n = 10) was administered.
      All animals were awakened and observed for 48 hrs. At 48 hrs, cardiac function,
      bacterial cultures from the septic focus, and inflammatory changes in the abdomen
      were quantified. MEASUREMENTS AND MAIN RESULTS: After resuscitation with
      acadesine vs. vehicle, we observed the following: a) arterial blood pressure and
      cardiac filling pressures were similar but cardiac index, systemic oxygen
      delivery, and systemic oxygen consumption were increased; b) plasma lactate was
      higher, systemic vascular resistance was lower, but ileal mucosal blood flow was
      not measurably altered; c) lipopolysaccharide-evoked tumor necrosis factor
      production in whole blood ex vivo was reduced; d) in those animals that survived
      48 hrs (10/10 vs. 8/10), sepsis-induced cardiac depression, amount of free
      intraperitoneal fluid, extra abscess inflammatory reaction, abscess wall
      formation, abscess bacterial counts, and peritoneal bacterial counts, were all
      similar, but blood bacterial counts were higher. CONCLUSIONS: Fluid resuscitation
      with acadesine produced no adverse hemodynamic consequences and probably improved
      washout of metabolites from the reperfused microcirculation in sites other than
      the small intestine or heart. Taken together, these observations suggest that
      adenosine regulating agents might have therapeutic potential during fluid
      resuscitation from trauma. However, at least in these extreme conditions, the
      acute salutary effects of acadesine were probably overwhelmed by polymicrobial
      sepsis. Further studies must determine whether supplemental adjuvants to boost
      host defense during recovery from trauma will optimize adenosine-based
      resuscitation solutions.

PMID- 10199539
TI  - Redox status of cytochrome a,a3: a noninvasive indicator of dysoxia in regional
      hypoxic or ischemic hypoxia.
AB  - OBJECTIVE: Multiwavelength near infrared (NIR) spectrophotometry can monitor the
      redox state of cytochrome a,a3 (cyt a,a3) in vivo. Because cyt a,a3 is the most
      immediate reductant of oxygen, this technique has been proposed to evaluate
      tissue oxygenation. The purpose of this study was to examine the relationship
      between cyt a,a3 oxidation level as an indicator of dysoxia and oxygen uptake
      (VO2) when oxygen delivery (DO2) was progressively lowered in an in situ
      vascularly isolated hindlimb. DESIGN: Prospective, randomized, laboratory study.
      SETTING: University research laboratory. SUBJECTS: Fourteen pigs. INTERVENTIONS:
      Measurement of critical values for both VO2 and cyt a,a3 oxidation during
      ischemic and hypoxic hypoxia. MEASUREMENTS AND MAIN RESULTS: The right hindlimb
      of anesthetized, paralyzed, and ventilated pigs was subjected to progressive
      ischemic or hypoxic hypoxia for 100 mins by ten stepwise decreases in DO2. In
      ischemic hypoxia (n = 7), arterial inflow (Q) from a pump-membrane oxygenator
      system was lowered from 50 to 0 mL/min, with PaO2 maintained at 100 mm Hg. In
      hypoxic hypoxia (n = 6), PaO2 was lowered from 100 mm Hg to 0 mm Hg. Hindlimb DO2
      was calculated as the product of Q and arterial oxygen content, and VO2 as the
      product of Q and arteriovenous difference. The cyt a,a3 oxidation level was
      measured every 10 secs with a four-wavelength spectrophotometer. These parameters
      were measured 9 mins after each change of DO2. Critical values for both VO2 and
      cyt a,a3 oxidation level as a function of DO2 were determined in each animal by
      dual linear regression analysis. In ischemic and hypoxic hypoxia, a strong
      correlation was found between cyt a,a3 oxidation level and VO2 in both ischemic
      and hypoxic hypoxia (r2 =.90 and .87, respectively). Hindlimb vascular resistance
      increased in ischemic hypoxia and decreased in hypoxic hypoxia when DO2 reached
      critical DO2. CONCLUSIONS: From these results, we concluded that monitoring the
      cyt a,a3 redox state by NIR spectrophotometry is, in this experimental setting, a
      sensitive indicator of dysoxia during regional hypoxic or ischemic hypoxia.

PMID- 10199540
TI  - Gas exchange and hemodynamics in experimental pleural effusion.
AB  - OBJECTIVE: To investigate the cardiorespiratory effects of graded bilateral
      pleural effusions in the anesthetized pig. DESIGN: Prospective, randomized,
      controlled, laboratory study. SETTING: Animal laboratory. SUBJECTS: Eleven male
      Yorkshire pigs. INTERVENTIONS: Animals were anesthetized using inhaled
      isoflurane. Orotracheal intubation was followed by mechanical ventilation.
      Bilateral chest tubes were inserted, and graded increasing pleural effusions were
      created using saline of 0, 20, 40, and 80 mL/kg, divided equally between each
      side. At each pleural volume, intravascular volume was randomly altered (by
      phlebotomy or transfusion of colloid) to normal (unchanged), low (decreased by 10
      mL/kg), or high (increased by 10 mL/kg). MEASUREMENTS AND MAIN RESULTS:
      Hemodynamic parameters, intrapleural pressures, hemoglobin, and blood gases were
      measured. At the lowest volume of pleural fluid, PaO2 was reduced by
      approximately 50% vs. baseline, whereas systemic hemodynamics were unchanged.
      PaO2 was reduced in a dose-dependent fashion as pleural volume increased but was
      not affected by alterations in intravascular volume. Intrapulmonary shunt was
      increased both by intrapleural volume in a dose-dependent fashion and by
      increases in intravascular volume at high levels of pleural volume. Cardiac
      output and systemic mean arterial pressure increased with elevated intravascular
      volume but were not influenced by lower levels of intrapleural volume. Mean
      pulmonary arterial pressure, central venous pressure, and pulmonary artery
      occlusion pressure were increased by elevations in both intrapleural volume and
      intravascular volume. Intrapleural pressure and pulmonary vascular resistance
      were related to intrapleural volume only. CONCLUSIONS: Hypoxemia occurs as an
      early event in acute bilateral pleural effusions and precedes hemodynamic
      decompensation. Oxygenation is independent of intravascular filling pressures,
      but hemodynamics are preserved with elevated filling pressures. Clinical studies
      should be undertaken to examine the risks/benefits of careful removal of pleural
      fluid in patients with pleural effusions, when oxygenation is impaired during
      mechanical ventilation.

PMID- 10199541
TI  - Large-pore hemodialysis in acute endotoxin shock.
AB  - OBJECTIVE: This study was undertaken to test the hypothesis that hemodialysis
      with a large-pore membrane would improve heart function during acute endotoxin
      shock. SETTING: Large animal laboratory. DESIGN: Eighteen mongrel dogs were
      instrumented to measure left ventricular maximum end-systolic elastance (left
      ventricular maximum elastance at end systole), cardiac output, circumflex artery
      blood flow, and myocardial mechanical efficiency (CO x MAP/MVO2, where CO is
      cardiac output, MAP is mean arterial pressure, and MVO2 is myocardial oxygen
      consumption). Plasma catecholamine concentrations were determined by high
      performance liquid chromatography. Endotoxin shock was induced by infusing 5.0
      microg/kg/min of Escherichia col 0127:B8 endotoxin in the portal vein for 60
      mins, followed by 2.0 microg/kg/min of constant infusion. Control dogs (n = 6)
      received 4.0 mL/kg/min of saline; hemodialysis dogs (n = 6) underwent venovenous
      hemodialysis in 50-min intervals using a polysulfone filter (1.2 m2; mean pore
      size, 0.50 nm; blood flow rate, 400 mL/min; ultrafiltrate, "zero-balanced");
      shams (n = 5) were treated identically to hemodialysis dogs, except that no
      convective dialysis was performed. A fourth group (n = 6) was treated with
      dopamine (5.0-7.0 microg/kg/min, optimal dose for contractile increase based on
      dose-response studies). MEASUREMENTS AND MAIN RESULTS: After 2 hrs of treatment,
      left ventricular maximum elastance at end systole increased and was unchanged in
      controls (30 +/- 5 mm Hg/mm) and shams (24 +/- 6 mm Hg/mm) compared with basal
      control. Hemodialysis treatment increased contractility (53 +/- 4 mm Hg/mm), as
      did dopamine treatment (54 +/- 7 mm Hg/mm). Endotoxin shock reduced mechanical
      efficiency to 45% of basal control; with hemodialysis treatment, left ventricular
      efficiency returned to 64% of basal control measurement, compared with 49% with
      dopamine treatment. During treatment, myocardial glucose uptake was increased
      with hemodialysis compared with other groups. No difference was observed among
      groups for left ventricular end-diastolic pressures or dimensions, or
      catecholamine concentrations. CONCLUSIONS: Large-pore hemodialysis increased left
      ventricular contractility to a similar degree as dopamine and provided a marginal
      improvement in myocardial glucose uptake and mechanical efficiency.

PMID- 10199542
TI  - Combined antithrombin III and C1-esterase inhibitor treatment decreases
      intravascular fibrin deposition and attenuates cardiorespiratory impairment in
      rabbits exposed to Escherichia coli endotoxin.
AB  - OBJECTIVE: To assess the effect of a combined antithrombin III and C1-esterase
      inhibitor treatment on intravascular organ fibrin deposition and
      cardiorespiratory changes following intravenous Escherichia coli endotoxin
      (lipopolysaccharide [LPS] 80 microg/kg i.v.) exposure. DESIGN: Prospective,
      randomized trial. SETTING: Research laboratory of a university medical center.
      SUBJECTS: Anesthetized, instrumented and mechanically ventilated rabbits
      ([Chbb:CH); n = 40). INTERVENTIONS: Endotoxin was given to 30 animals. Ten
      animals received no inhibitor (endotoxin control group). The other animals were
      either treated by high-dose (300 units/kg; n = 10) or low-dose (100 units/kg; n =
      10) combined antithrombin III and C1-esterase inhibitor administration. Ten
      rabbits (time control group) were given placebo (sodium chloride 0.9%).
      Cardiorespiratory variables were assessed at baseline, 120 mins, and 240 mins
      after endotoxin or placebo administration. Four hours after endotoxin injection,
      liver, lung, and kidney tissue samples were examined for intravascular fibrin
      deposition by light microscopy. MEASUREMENTS AND MAIN RESULTS: Inhibitor
      treatment significantly decreased clot formation in lungs and livers without,
      however, demonstrating a clear dose-dependent effect. Combined antithrombin
      III/C1-esterase treatment attenuated the decrease of mean arterial pressure and
      cardiac output observed following endotoxin injection. Blood pressure improvement
      was significantly dependent on dosage administered. CONCLUSION: Combination of
      antithrombin III and C1-esterase inhibitor treatment during early endotoxin shock
      decreased organ fibrin deposition and improved cardiovascular stability.

PMID- 10199543
TI  - Hypertonic saline without or with dextran-70 in the treatment of experimental
      acute myocardial ischemia and reperfusion.
AB  - OBJECTIVE: To evaluate the effects of treatment with hypertonic saline without
      (HS) or with dextran (HSD) on cardiac function and myocardial damage during
      reperfusion after acute myocardial ischemia. DESIGN: A prospective, randomized,
      controlled study. SETTING: Animal laboratory at a university medical center.
      SUBJECTS: Three-month-old male, crossbred (Swedish landrace, Yorkshire, and
      Hampshire) pigs. INTERVENTIONS: The pigs were anesthetized and catheterized. A
      mid-sternal thoracotomy was performed, the pericardial sac was opened, and the
      left anterior descending artery was dissected free and occluded for 45 mins. A 10
      min treatment period with 4 mL/kg HS (7.5%), HSD (7.5%/6%), or normal saline
      (0.9%) was started 5 mins before reperfusion. After a reperfusion period of 240
      mins, biopsies from the ischemic area were taken. Thereafter, the hearts were
      excised and subjected to a staining procedure (triphenyltetrazoliumchloride and
      Evan's blue), and the left ventricle was sliced for assessment of the size of the
      infarcted area and the area at risk. MEASUREMENTS AND MAIN RESULTS: Central
      hemodynamics and myocardial performance were monitored before, during, and for
      240 mins after 45 mins of acute left anterior descending artery occlusion.
      Alterations in blood chemistry and serum levels of markers of myocardial damage
      were repeatedly analyzed during the experimental procedure. Biopsies from the
      injured myocardium were analyzed for adenosine triphosphate, adenosine 5'
      diphosphate, adenosine monophosphate, creatine phosphate, lactate, and glucose.
      Infarct sizes and areas at risk were planimetrically quantified. HS was not found
      to enhance, but rather to depress, cardiac performance at reperfusion, whereas
      HSD improved hemodynamics and myocardial contractility. HS or HSD administration
      was not found to increase the ischemia-induced myocardial damage. CONCLUSIONS:
      The administration of HSD but not HS will improve hemodynamics and myocardial
      performance during reperfusion after 45 mins of myocardial ischemia. The
      documented myocardial ischemic injury was not affected by any of the fluid
      therapies. Therefore, the present data do not support previously suggested
      detrimental effects of HS on myocardial ischemic injury.

PMID- 10199544
TI  - Volume of ventricular blood is an important determinant of outcome in
      supratentorial intracerebral hemorrhage.
AB  - OBJECTIVE: To determine the prognostic significance and pathophysiologic
      implication of intraventricular extension of supratentorial intracerebral
      hemorrhage. DESIGN: Prospective study. SETTING: Acute stroke and neurointensive
      care units of a tertiary care hospital. PATIENTS: One hundred twenty-nine
      patients with supratentorial intracerebral hemorrhage, managed medically.
      INTERVENTIONS: Two patients had intraventricular catheters placed for external
      drainage. No patient received thrombolytics or surgical evacuation of clot.
      MEASUREMENTS AND MAIN RESULTS: Of the 129 patients, 47 had intraventricular
      extension of their hemorrhages. These patients had larger intraparenchymal
      hemorrhages (36.6 cm3 vs. 15.0 cm3) and lower initial Glasgow Coma Scale scores
      (mean, 9.6 vs. 13.7). Their 30-day mortality rate was 43% compared with only 9%
      among those without ventricular extension. Univariate and multivariate logistic
      regression modeling was used to assess the prognostic significance of various
      measures of intraventricular hemorrhage. The presence of intraventricular
      hemorrhage, the number of ventricles containing blood, fourth ventricular blood,
      and intraventricular hemorrhage volume were each related to 30-day mortality in a
      univariate analysis, but only intraventricular hemorrhage volume contributed
      significantly to outcome prediction in the presence of Glasgow Coma Scale score.
      CONCLUSIONS: Volume of intraventricular hemorrhage is an important determinant of
      outcome in supratentorial intracerebral hemorrhage.

PMID- 10199545
TI  - Syndrome of inappropriate antidiuretic hormone secretion in children following
      spinal fusion.
AB  - OBJECTIVES: a) To determine if antidiuretic hormone (ADH) is elevated in patients
      undergoing spinal fusion, especially in those who have clinical evidence of
      syndrome of inappropriate antidiuretic hormone (SIADH); b) to evaluate the
      relationship between ADH secretion and the secretion of atrial natriuretic
      peptide (ANP). SETTING: Tertiary care pediatric intensive care unit (ICU) in a
      university hospital. DESIGN: A prospective cross-sectional, observational study
      with factorial design. PATIENTS: Thirty patients > or = 10 yrs of age undergoing
      spinal fusion admitted to the ICU for postoperative care. INTERVENTIONS: Patients
      underwent anterior, posterior, or both anterior/posterior spinal fusion. Blood
      was collected for serial measurements of ADH, ANP and serum electrolyte levels.
      Heart rate, blood pressure and central venous pressure were measured.
      MEASUREMENTS AND MAIN RESULTS: Thirty children were studied. Nineteen had
      idiopathic scoliosis, nine had neuromuscular scoliosis, one had Marfan's disease,
      and one had congenital scoliosis. Ten (33%) children met clinical criteria of
      SIADH. There was no difference in duration of surgery, blood loss, volume of iv
      fluid administration pre- and intraoperatively, or type of scoliosis between
      those who developed SIADH and those who did not. Hemodynamic variables were
      similar in both groups. ADH levels increased in both groups immediately
      postoperatively and at 6 hrs after surgery, but were much more elevated in those
      patients with SIADH. Patients with SIADH also had significantly higher ADH levels
      preoperatively. In relation to serum osmolality, ADH was considerably higher in
      those with SIADH compared with those who did not. Although ANP values tended to
      be higher in the group with SIADH, this did not reach statistical significance.
      CONCLUSION: SIADH occurs in a subset of children who undergo spinal fusion. The
      diagnosis of SIADH can be made easily using clinical parameters which are well
      defined. In the face of SIADH, continued volume expansion may be harmful, and
      should therefore be avoided.

PMID- 10199546
TI  - No evidence for cerebral hypoperfusion during cerebral malaria.
AB  - OBJECTIVE: Among the mechanisms suggested for altered consciousness during
      cerebral malaria is the hypothesis of cerebral ischemia, which remains
      controversial, with little supportive O2 conflicting hemodynamic data. The
      purpose of this study was to test the hypothesis that cerebral ischemia is a main
      mechanism for altered consciousness during cerebral malaria. SETTING: University
      hospital pediatric ward in a region with endemic cerebral malaria. DESIGN:
      Prospective evaluation of cerebral hemodynamics and cerebral oxygenation during
      cerebral malaria compared with severe malaria anemia without altered
      consciousness. PATIENTS: During a 2-wk period, we evaluated all patients who were
      admitted for cerebral malaria (n = 5). Age-matched patients admitted for severe
      malaria anemia without altered consciousness (n = 3) and outpatients (n = 3) were
      investigated for comparison. INTERVENTIONS: All patients received the usual
      treatment according to their needs, which was determined by the physician in
      charge. Repeated neurologic evaluations were performed during the early
      management period in patients with cerebral malaria. METHODS AND MAIN RESULTS: We
      repeatedly measured cerebral blood flow velocity (transcranial Doppler) and
      simultaneous systemic determinants of cerebral blood flow (arterial pressure,
      arterial oxygen saturation, PaCO2, rectal temperature, and hemoglobin
      concentration). The adequacy of cerebral blood flow to oxygen demands during
      cerebral malaria was assessed by continuous recording of jugular bulb venous
      oxygen saturation (using a fiberoptic device). Marked cerebral vasodilation was
      observed during cerebral malaria (systolic velocity, 1.45 +/- 0.09 m/s; diastolic
      velocity, 0.75 +/- 0.08 m/s; n = 4) and during severe malaria anemia (systolic
      velocity, 1.18 +/- 0.14 m/s; diastolic velocity, 0.55 +/- 0.05 m/s; n = 3)
      compared with control children (systolic velocity, 0.84 +/- 0.13 m/s; diastolic
      velocity, 0.35 +/- 0.06 m/s; n = 3; p < .05). During cerebral malaria, jugular
      bulb venous oxygen saturation remained stable, including during neurologic
      recovery, with initial values of 67.5 +/- 4.3%. CONCLUSIONS: Because jugular bulb
      venous oxygen saturation remained within the normal range, cerebral hyperemia
      seems to be an adaptive response to altered systemic determinants, which argues
      against a hemodynamic mechanism for altered consciousness during cerebral
      malaria.

PMID- 10199548
TI  - Practice parameters for hemodynamic support of sepsis in adult patients in
      sepsis. Task Force of the American College of Critical Care Medicine, Society of
      Critical Care Medicine.
AB  - OBJECTIVE: To present guidelines for hemodynamic support of adult patients with
      sepsis. PARTICIPANTS: An international task force of nine experts in disciplines
      related to critical care medicine was convened from the membership of the Society
      of Critical Care Medicine. EVIDENCE: Review of published literature and expertise
      and personal experience of task force. The strength of evidence of human studies
      was classified according to study design and scientific value. CONSENSUS PROCESS:
      The task force met several times in person and communicated by electronic mail to
      identify the pertinent literature and arrive at consensus recommendations.
      Consideration was given to the relationship between the weight of scientific
      evidence and the experts'opinions. Draft documents were composed and debated by
      the task force until consensus was reached. The strength of recommendations was
      graded according to evidenced-based guidelines. CONCLUSIONS: The panel formulated
      an underlying approach to the hemodynamic support of sepsis. Hemodynamic
      therapies should be titrated to specific and definable endpoints. The effects of
      therapy should be assessed by monitoring a combination of parameters of global
      and regional perfusion. Using this approach, the panel made specific
      recommendations for fluid resuscitation, vasopressor therapy, and inotropic
      therapy of septic patients.

PMID- 10199547
TI  - Guidelines for intensive care unit admission, discharge, and triage. Task Force
      of the American College of Critical Care Medicine, Society of Critical Care
      Medicine.
AB  - OBJECTIVE: To provide guidelines for admission, discharge, and triage of adult
      patients to the intensive care unit (ICU), based on expert opinion and the
      relevant literature. DATA SOURCES: Publications relevant to the admission,
      discharge, and triage of patients to the ICU were obtained from the medical
      literature. STUDY SELECTION: Not applicable. DATA EXTRACTION: Articles were
      reviewed and the relevant information extracted for analysis by an expert panel.
      DATA SYNTHESIS: The articles were reviewed and graded levels of recommendation
      made based on a rating system described in the text. CONCLUSIONS: Although little
      scientifically rigorous data exist validating the criteria for admission,
      discharge, and triage of adult patients to the ICU, current literature and expert
      opinion support guidelines to streamline the admission, discharge, and triage
      process.

PMID- 10199549
TI  - Nonsurgical treatment of a severe tracheal rupture after endotracheal intubation.
AB  - OBJECTIVE: We report the case of an 82-yr-old woman with a large complete
      longitudinal tracheal rupture, following endotracheal intubation. The patient was
      treated nonoperatively with excellent outcome. The diagnostic and therapeutic
      course as well as other therapeutic options are discussed.

PMID- 10199550
TI  - Differential behavior of E-cadherin and occludin in their colocalization with ZO
      1 during the establishment of epithelial cell polarity.
AB  - At the initial stage of cell-cell contact of epithelial cells, primordial spot
      like junctions are formed at the tips of thin cellular protrusions radiating from
      adjacent cells, where E-cadherin and ZO-1 are precisely coconcentrated (Yonemura
      et al., 1995, J. Cell Sci. 108:127-142). In fully polarized epithelial cells, E
      cadherin and ZO-1 are completely sorted into belt-like adherens junctions (AJ)
      and tight junctions (TJ), respectively. Here we examined the behavior of
      occludin, an integral membrane protein consisting of TJ, during the establishment
      of epithelial cell polarity. Using confocal immunofluorescence microscopy, we
      quantitatively compared the spatial relationship of occludin/ZO-1 with that of E
      cadherin/ZO-1 during epithelial cellular polarization by replating or wounding
      cultured mouse epithelial cells (MTD1-A). At the initial stage of cell-cell
      contact, E-cadherin and ZO-1 appeared to be simultaneously recruited to the
      primordial form of spot-like junctions at the tips of cellular processes which
      showed no concentration of occludin. Then, as cellular polarization proceeded,
      occludin was gradually accumulated at the ZO-1-positive spot-like junctions to
      form belt-like TJ, and in a complementary manner E-cadherin was sorted out from
      the ZO-1-positive spot-like junctions to form belt-like AJ. The molecular
      mechanism of TJ/AJ formation during epithelial cellular polarization is discussed
      with special reference to the roles of ZO-1.

PMID- 10199551
TI  - POU family transcription factors in the nervous system.
AB  - The POU (Pit-Oct-Unc) family of transcription factors was originally defined on
      the basis of a common DNA binding domain in the mammalian factors Pit-1, Oct-1,
      and Oct-2 as well as the nematode protein Unc-86. Subsequently, a number of other
      POU family factors have been identified in both vertebrates and invertebrates.
      Many of these original and subsequently isolated members of the family have been
      shown to play critical roles in the development and functioning of the nervous
      system. To exemplify this, studies are described involving the functional
      characterisation of the Oct-2 factor, one of the original POU factors, and of the
      Brn-3 factors, which were isolated subsequently and are the mammalian factors
      most closely related to Unc-86.

PMID- 10199552
TI  - Transcriptional control by cell-cycle regulators: a review.
AB  - In eukaryotes, progression of the cell cycle is associated with periodic
      transcription activation/repression of growth-regulatory genes. We summarize here
      current knowledge and views on the role of critical cell-cycle regulators such as
      the retinoblastoma pocket family members and cyclin-dependent kinases in the
      regulation of gene transcription. In particular, we discuss here the role of
      specific cyclin-dependent kinase complexes in the regulation of basal
      transcription. Although the functional connections between transcription and cell
      cycle regulators is far from being understood, recent progress has been made in
      connecting cell-cycle progression to dedicated components of the RNA polymerase
      II transcription apparatus complex.

PMID- 10199553
TI  - Hyaluronic acid enhances proliferation and chondroitin sulfate synthesis in
      cultured chondrocytes embedded in collagen gels.
AB  - The effects of hyaluronic acid (HA) on the proliferation and chondroitin sulfate
      (CS) synthesis of chondrocytes embedded in collagen gels were examined. Articular
      cartilage was isolated from the humerus, femur, and tibia of 21 10-week-old
      Japanese white rabbits. Chondrocytes isolated by collagenase digestion were
      embedded in type I collagen gels and cultured in Dulbecco's modified Eagle's
      medium (DMEM) with various doses of HA for 4 weeks. Histological and biochemical
      evaluations were performed at postculture weeks 1, 2, 3, and 4. For biochemical
      evaluations, isomers such as chondroitin 6-sulfate (delta(di)-6S) and chondroitin
      4-sulfate (delta(di)-4S) synthesized by cultured chondrocytes were determined by
      high performance liquid chromatography (HPLC) combined with fluorometry.
      Morphological and histological studies demonstrated that HA-treated chondrocytes
      in collagen gel proliferated profusely while maintaining their phenotype. At
      postculture week 4, 0.1 mg/ml of HA induced an eightfold increase in cell counts
      compared with HA pretreatment values, or 1.5-fold more than control group.
      Synthesis of delta(di)-6S (delta(di)-6S content/cell) in groups treated with 0.01
      and 0.1 mg/ml of HA significantly increased, while gel accumulation rates in
      groups treated with 0.1 and 1.0 mg/ml of HA scored significantly higher values
      than other groups. In collagen gel culture, HA enhanced the proliferation and
      delta(di)-6S synthesis of chondrocytes while maintaining their phenotype. In
      clinical application, since the supply of autologous chondrocytes for
      transplantation is not unlimited, the HA-treated culture method may be useful for
      increasing the number of chondrocytes and thus improving the quality of implants.

PMID- 10199554
TI  - Hyperoxia causes decreased expression of vascular endothelial growth factor and
      endothelial cell apoptosis in adult retina.
AB  - Mice or humans with photoreceptor degenerations experience permeability and
      dropout of retinal capillaries. Loss of photoreceptors results in decreased
      oxygen usage and thinning of the retina with increased oxygen delivery to the
      inner retina. To investigate the possibility that increased tissue oxygen plays a
      role in the vascular damage, we exposed adult mice to hyperoxia, which also
      increases oxygen in the retina. After 1, 2, or 3 weeks of hyperoxia, there was a
      statistically significant decrease in retinal vascular density that was not
      reversible, and endothelial cell apoptosis was demonstrated by TUNEL staining.
      Mice exposed to hyperoxia and mice with photoreceptor degeneration both showed
      decreased expression of VEGF in the retina. After complete or near-complete
      degeneration of photoreceptors, there was increased expression of VEGF in RPE
      cells, which may explain the association of photoreceptor degeneration and
      neovascularization in or around the RPE. Increased expression of VEGF in
      photoreceptors of transgenic mice failed to prevent hyperoxia-induced retinal
      capillary dropout. These data suggest that increased oxygen in the retina, either
      by increased inspired oxygen or by photoreceptor degeneration, results in
      endothelial cell death and dropout of capillaries. Decreased expression of VEGF
      may be a contributing factor, but the situation may be more complicated for
      mature retinal vessels than it is for immature vessels, because VEGF replacement
      does not rescue mature retinal vessels, suggesting that other factors may also be
      involved.

PMID- 10199555
TI  - Regulation of actin cytoskeleton in lymphocytes: PKC-delta disrupts IL-3-induced
      membrane ruffles downstream of Rac1.
AB  - In the murine pre-B lymphoid cell line Baf3, the presence of IL-3 is required for
      the formation of membrane ruffles that intensely stain for actin and are
      responsible for the elongated cell phenotype. Withdrawal of IL-3 dissolves
      ruffled protrusions and converts the cell phenotype to round. Flow cytometric
      analysis of the cell shape showed that an inactive analog of Rac1 but not
      inactive RhoA or inactive cdc42 rounds the cells in the presence of IL-3.
      Constitutively activated Rac1 restores the elongated cell phenotype to IL-3
      starved cells. We conclude that the activity of Rac1 is necessary and sufficient
      for the IL-3-induced assembly of membrane ruffles. Similar to the IL-3
      withdrawal, phorbol 12-myristate 13-acetate (PMA) dissolves actin-formed membrane
      ruffles and rounds the cells in the presence of IL-3. Flow cytometric analysis of
      the cell shape demonstrated that in the presence of IL-3 the PMA-induced cell
      rounding cannot be abolished by constitutively active Rac1 but can be imitated by
      inactive Rac1. These data indicate that PMA disrupts the IL-3 pathway downstream
      of Rac1. Cells rounded by PMA return to the elongated phenotype concomitantly
      with PKC depletion. PMA-induced cell rounding can be reversed by the PKC-specific
      inhibitor GF109203X. Experiments with overexpression in Baf3 of individual PKC
      isoforms and a dominant negative PKC-delta indicate that activation of PKC-delta
      but not other PKC isoforms is responsible for disruption of membrane ruffles.

PMID- 10199556
TI  - Fra-1 potentiates osteoclastic differentiation in osteoclast-macrophage precursor
      cell lines.
AB  - c-Fos, a component of the dimeric transcription factor AP-1, is necessary for
      osteoclast formation. To determine whether c-Fos can substitute for any or all of
      the stimuli needed for osteoclast induction, we infected osteoclast precursors
      with retroviral vectors expressing c-Fos or the Fos-related protein, Fra-1. The
      infected cells were incubated with or without osteoclast-inductive stimuli.
      Osteoclast formation from retroviral-infected precursors remained completely
      dependent on osteoclast-inductive stromal cells. Unexpectedly, infection of
      bipotential osteoclast-macrophage precursor cell lines with retroviruses
      expressing Fra-1 but not c-Fos caused a 10-100-fold increase in the number of
      precursors that developed calcitonin receptors associated with an increase in
      bone resorption. These observations suggest that, in the precursor cell lines,
      Fra-1 is a limiting factor for full responsiveness to the osteoclast-inductive
      environment. Fra-1 is therefore likely to play a role in osteoclast
      differentiation which is distinct from that of c-Fos.

PMID- 10199557
TI  - Cytoplasmic elongation and rupture in megakaryoblastic leukemia cells via
      activation of adhesion and motility by staurosporine on fibronectin-bound
      substratum.
AB  - Human megakaryoblastic leukemia Meg-01 cells were attached to fibronectin (FN)
      coated substratum, on which remarkable spreading and cytoplasmic elongation was
      induced by treatment with a protein kinase inhibitor, staurosporine (stp). This
      effect was inhibited by RGDS and was also not seen on FN-lacking substratum. The
      extended cytoplasm had swollen terminals and nodes, which contained GpIIb and
      beta-thromboglobulin, occasionally included alpha granules, and tended to form
      particles (2-5 microm) after rupture of the narrowed cytoplasm. Among other
      protein kinase modulators tested, only K252a promoted the elongation, while
      calphostin, herbimycin, TPA, and calyculin suppressed it. The cells began to
      migrate soon after addition of stp, with attachment to the substratum held at
      some sites during the migration. This tethered movement seemed to cause the
      cytoplasmic elongation and the rupture into particles. The elongation was
      retarded by pretreating the cells with cytochalasin A and Clostridium C3 toxin
      but not with demecolcine. Actin microfilaments in the stp-treated Meg-01 cells
      accumulated in the filopodia and periphery of the extended cytoplasm, in which
      vinculin was colocalized as adhesion plaques. The microtubules were
      longitudinally oriented through the cytoplasmic extension and showed no ring
      profile in the nodes and particles. Thus, stp in the presence of FN appears to
      stimulate reorganization of actin-based cytoskeleton and formation of focal
      contacts in Meg-01 cells. This leads to the activation of cell adhesion and
      motility, and then cytoplasmic elongation and rupture into particles.

PMID- 10199558
TI  - Role of NFkappaB in the regulation of macrophage colony stimulating factor by
      tumor necrosis factor-alpha in ST2 bone stromal cells.
AB  - Expression of MCSF in bone is important to the regulation of osteoclastogenesis.
      We show here that tumor necrosis factor-alpha (TNFalpha) increases the production
      of both soluble (sMCSF) and membrane-bound (mMCSF) macrophage colony stimulating
      factor by ST2 bone stromal cells. Treatment of ST2 cells with TNFalpha caused
      sMCSF levels to increase by 394+/-5% from basal; mMCSF rose by 316+/-66% from
      30+/-10 per 100,000 cells in the same time. These increases were consistent with
      increased expression of mRNAs encoding both isoforms. Increases in MCSF mRNA are
      also seen after stimulation with dexamethasone. To investigate the potential role
      of NFkappaB in this TNFalpha effect, we treated cells with sodium salicylate
      (NaS), an inhibitor of NFkappaB translocation. NaS decreased TNFalpha-stimulated
      NFkappaB activation by 50% as assessed by EMSA. Despite inhibition of NFkappaB
      signaling, NaS enhanced TNFalpha-stimulated MCSF secretion and did not prevent
      TNFalpha-stimulated increases in sMCSF mRNA, suggesting that NFkappaB was not
      involved in TNFalpha effect on the gene. TNFalpha failed to stimulate
      transcription of a 774 nucleotide MCSF promoter-luciferase reporter transfected
      into ST2 cells which contained the NFkappaB consensus sequence. Deletion of the
      seven nucleotides containing the NFkappaB homology response sequence from the
      MCSF promoter increased basal gene transcription by twofold. TNFalpha thus
      contributes to an osteoclastogenic environment through upregulation of bone
      expression of both MCSF isoforms. Our data suggests that NFkappaB is not the
      major signaling pathway through which this occurs.

PMID- 10199559
TI  - Expression of insulin-like growth factor binding protein-3 (IGFBP-3) in human
      keratinocytes is regulated by EGF and TGFbeta1.
AB  - Insulin-like growth factor-I (IGF-I) is essential for normal epidermal
      homeostasis; however, the role of IGF binding proteins (IGFBPs), regulators of
      IGF action, remains unclear. Here we examine the regulation of human keratinocyte
      produced IGFBPs by epidermal growth factor (EGF), transforming growth factor beta
      1 (TGFbeta1), and IGF-I, growth factors known to be active in skin. In the
      absence of added growth factors, IGFBP-3 was the major binding protein secreted
      into the medium by primary keratinocytes. Addition of EGF or TGFbeta1 to
      keratinocyte cultures resulted in a significant decrease in IGFBP-3 abundance in
      conditioned medium when compared with control, untreated cells. Specifically, EGF
      (50 ng/ml) and TGFbeta1 (50 ng/ml) reduced IGFBP-3 abundance to 15+/-6% and 22+/
      9%, respectively. Using Northern blot analysis, we found EGF and TGFbeta1 (50
      ng/ml) to reduce IGFBP-3 mRNA levels in keratinocytes to 51+/-12% and 50+/-38%,
      respectively, when compared with control, untreated cells. Treatment with IGF-I
      or its analogue des(1-3)IGF-I did not lead to any consistent change in IGFBP-3
      abundance. However, both IGF-I and des(1-3)IGF-I at 100 ng/ml led to a modest
      increase in IGFBP-3 mRNA levels in keratinocytes, suggesting posttranscriptional
      regulation of IGFBP-3 abundance. We propose that local modulation of IGFBP-3
      abundance may represent another level of regulation of growth factor action in
      the epidermis, where EGF and TGFbeta1 and possibly other local growth factors
      specifically regulate the availability of IGF-I to its keratinocyte receptors.

PMID- 10199560
TI  - Ca(2+)- and protein kinase C-dependent stimulation of mitogen-activated protein
      kinase in detergent-skinned vascular smooth muscle.
AB  - Protein kinase C and mitogen-activated protein (MAP) kinase are expressed in all
      smooth muscle cells and believed to be important in several physiologically
      relevant properties of this muscle. Our goal was to determine if protein kinase C
      and MAP kinase are activated by a simple increase in cellular Ca(2+) and to
      determine if protein kinase C is an upstream activator of MAP kinase. These
      studies were performed in the Triton X-100 detergent-skinned preparation of the
      swine carotid artery, which allows control of the intracellular environment
      without influence from membrane or receptor-mediated modulation. The p42 and p44
      isoforms of MAP kinase were activated in a concentration-dependent fashion by an
      increase in Ca2+. This was shown by in-the-gel kinase assay and direct
      measurement of MAP kinase phosphotransferase activity. Protein kinase C was also
      activated by an increase in Ca2+, as shown by a novel assay that measures total
      active protein kinase C in the tissue. Inhibition of protein kinase C activity
      completely abolished MAP kinase activity. Additionally, inhibition of
      Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) also abolished MAP
      kinase activity. Using intact swine carotid arteries, we showed p42 and p44 MAP
      kinase to be activated by both histamine and phorbol dibutyrate, but only the p42
      isoform was calcium-sensitive. Our results suggest that a Ca(2+)-dependent
      isoform of protein kinase C and CaM kinase II are upstream activators of MAP
      kinase in the swine carotid artery.

PMID- 10199561
TI  - Peroxisome proliferation, adipocyte determination and differentiation of
      C3H10T1/2 fibroblast cells induced by humic acid: induction of PPAR in diverse
      cells.
AB  - Humic acid, a high-molecular-weight polyphenolic compound, exists abundantly in
      soil, natural water, and various terrestrial and aquatic environments. Humic acid
      causes peroxisome proliferation in mouse liver and induces the expression of
      peroxisome proliferator activated receptor (PPAR) in BNL CL.2 cells. Both
      cytotoxicity and flow cytometry show that humic acid inhibits the growth of
      C3H10T1/2 cells at G1 phase. C3H10T1/2 fibroblast cells express PPARgamma and the
      adipocyte P2 (aP2) genes which convert into adipocytes after being treated with
      humic acid. Our findings may provide a unique model for studying the molecular
      control of determination and differentiation of mesodermal cell lineages.

PMID- 10199562
TI  - Interleukin-1 alpha induced cyclooxygenase-2 expression in bone-derived
      endothelial cells.
AB  - Histological studies have suggested that vascular endothelial cells in bone are
      members of a complex network that regulates bone development and remodeling by
      producing soluble factors or by mediating cell-cell adhesion. To clarify the role
      of bone-derived endothelial cell lines (BDECs) in bone remodeling, we established
      several clones of BDECs from the femurs of BALB/c mice after transformation with
      the SV40 virus. Then we examined the response of these clones to interleukin
      1alpha (IL-1alpha). IL-1alpha is known to induce bone resorption in part by
      increasing the expression of cyclooxygenase-2 (COX-2) that is associated with the
      production of PGE2 in osteoblast-lineage cells. Treating the primary and
      established BDECs with IL-1alpha induced COX-2 mRNA expression. A transcriptional
      activation assay revealed that the treatment with IL-1alpha increased COX-2
      promoter activity in a dose-dependent manner, and IL-1alpha promoted COX-2
      protein expression in BDECs. Treatment with IL-1alpha promoted PGE2 production
      from BDECs in a dose-dependent manner. These results indicate that IL-1alpha
      stimulates PGE2 synthesis largely by inducing BDECs to express COX-2. Because
      PGE2 stimulates bone resorption, these vascular endothelial cells, as well as
      osteoblast cells, play important roles in bone remodeling.

PMID- 10199563
TI  - From cell cycle regulation to angiogenesis: dialogue between the basic and
      clinical sciences.
AB  - Basic research in biological and medical disciplines has revealed fundamental
      aspects of the differentiation of single cells as well as the development of
      multicellular organisms. The combination of knowledge of intracellular and
      intercellular pathways controlling development and homeostasis in higher
      organisms is the key to understanding certain diseases that are associated with
      abnormalities in these pathways and developing strategies for fighting them.
      Today's high scientific output in a rapidly growing number of scientific journals
      requires great effort to keep up with the latest developments outside one's
      specialization. The tenth international conference of the International Society
      of Differentiation (ISD) therefore was a great opportunity for scientists of
      diverse fields of biological and medical research to learn about the latest
      developments in even remotely related branches of research and opening new
      perspectives. The authors have tried to conserve this spirit in reviewing main
      aspects of research presented at the conference.

PMID- 10199564
TI  - Decreased steady-state insulin-like growth factor binding protein-3 (IGFBP-3)
      mRNA level is associated with differentiation of cultured porcine myogenic cells.
AB  - Insulin-like growth factor binding proteins (IGFBPs) affect the biological
      activity of IGF-I in several cell types, including cultured muscle cells.
      Additionally, at least one of the IGFBPs, IGFBP-3, has been shown to have IGF
      independent effects on cell proliferation. Numerous studies have shown that
      immortalized muscle cell lines produce various IGFBPs, but to date no muscle cell
      line has been reported to produce IGFBP-3 protein or mRNA. Unlike muscle cell
      lines, primary cultures of porcine embryonic myogenic cells express IGFBP-3 mRNA
      and secrete a protein that is immunologically identifiable as IGFBP-3.
      Additionally, steady-state IGFBP-3 levels change significantly during
      differentiation. Here we report that differentiation of porcine myogenic cells in
      an IGFBP-3-free medium is accompanied by reduced steady-state IGFBP-3 mRNA
      levels. Steady-state levels of IGFBP-3 mRNA decreased approximately sevenfold (P
      < .05) during differentiation and then increased to predifferentiation levels
      once differentiation was complete. Addition of TGF-beta1 (0.5 ng/ml) to porcine
      myogenic cultures suppressed fusion and resulted in a sevenfold increase in
      steady-state IGFBP-3 mRNA and a 1.8-fold increase in IGFBP-3 protein levels as
      compared to untreated control cultures (P < .05). Results suggest that
      alterations in IGFBP-3 mRNA and protein may play a role in differentiation of
      porcine embryonic muscle cells.

PMID- 10199565
TI  - U2AF35 is encoded by an essential gene clustered in an operon with
      RRM/cyclophilin in Caenorhabditis elegans.
AB  - In most species the 3' splice site is recognized initially by an interaction
      between the two-subunit splicing factor U2AF with the polypyrimidine (poly(Y))
      tract that results in recruitment of the U2 snRNP to the branch-point consensus
      just upstream. In contrast, in Caenorhabditis elegans, both the poly(Y) tract and
      the branch-point consensus sequences are missing, apparently replaced by the
      highly conserved U4CAG/R 3' splice site consensus. Nevertheless C. elegans U2AF65
      is very similar to its mammalian and fly counterparts and may recognize the 3'
      splice site consensus. Here we report the cloning of the C. elegans U2AF35 gene,
      uaf-2. We show that it lacks an identifiable RS domain, which, in flies, has been
      shown to play a role in RNA binding, but it contains an extended glycine-rich
      stretch at its C-terminus. uaf-2 is in an operon with cyp-13, a gene that encodes
      a cyclophilin with an RRM domain at its N-terminus. We demonstrate by RNA
      interference that both U2AF genes, uaf-1 (which encodes U2AF65) and uaf-2, are
      required for viability, whereas cyp-13 is apparently not.

PMID- 10199566
TI  - The peculiar architectural framework of tRNASec is fully recognized by yeast
      AspRS.
AB  - The wild-type transcript of Escherichia coli tRNASec, characterized by a peculiar
      core architecture and a large variable region, was shown to be aspartylatable by
      yeast AspRS. Similar activities were found for tRNASec mutants with methionine,
      leucine, and tryptophan anticodons. The charging efficiency of these molecules
      was found comparable to that of a minihelix derived from tRNAAsp and is accounted
      for by the presence of the discriminator residue G73, which is a major aspartate
      identity determinant. Introducing the aspartate identity elements from the
      anticodon loop (G34, U35, C36, C38) into tRNASec transforms this molecule into an
      aspartate acceptor with kinetic properties identical to tRNAAsp. Expression of
      the aspartate identity set in tRNASec is independent of the size of its variable
      region. The functional study was completed by footprinting experiments with four
      different nucleases as structural probes. Protection patterns by AspRS of
      transplanted tRNASec and tRNAAsp were found similar. They are modified,
      particularly in the anticodon loop, upon changing the aspartate anticodon into
      that of methionine. Altogether, it appears that recognition of a tRNA by AspRS is
      more governed by the presence of the aspartate identity set than by the
      structural framework that carries this set.

PMID- 10199567
TI  - The uridine in "U-turn": contributions to tRNA-ribosomal binding.
AB  - "U-turns" represent an important class of structural motifs in the RNA world,
      wherein a uridine is involved in an abrupt change in the direction of the
      polynucleotide backbone. In the crystal structure of yeast tRNAPhe, the invariant
      uridine at position 33 (U33), adjacent to the anticodon, stabilizes the exemplar
      U-turn with three non-Watson-Crick interactions: hydrogen bonding of the 2'-OH to
      N7 of A35 and the N3-H to A36-phosphate, and stacking between C32 and A35
      phosphate. The functional importance of each noncanonical interaction was
      determined by assaying the ribosomal binding affinities of tRNAPhe anticodon stem
      and loop domains (ASLs) with substitutions at U33. An unsubstituted ASL bound 30S
      ribosomal subunits with an affinity (Kd = 140+/-50 nM) comparable to that of
      native yeast tRNAPhe (Kd = 100+/-20 nM). However, the binding affinities of ASLs
      with dU-33 (no 2'-OH) and C-33 (no N3-H) were significantly reduced (2,930+/-140
      nM and 2,190+/-300 nM, respectively). Surprisingly, the ASL with N3-methyluridine
      33 (no N3-H) bound ribosomes with a high affinity (Kd = 220+/-20 nM). In
      contrast, ASLs constructed with position 33 uridine analogs in nonstacking,
      nonnative, and constrained conformations, dihydrouridine (C2'-endo), 6
      methyluridine (syn) and 2'O-methyluridine (C3'-endo) had almost undetectable
      binding. The inability of ASLs with 6-methyluridine-33 and 2'O-methyluridine-33
      to bind ribosomes was not attributable to any thermal instability of the RNAs.
      These results demonstrate that proton donations by the N3-H and 2'OH groups of
      U33 are not absolutely required for ribosomal binding. Rather, the results
      suggest that the overall uridine conformation, including a dynamic (C3'-endo >
      C2'-endo) sugar pucker, anti conformation, and ability of uracil to stack between
      C32 and A35-phosphate, are the contributing factors to a functional U-turn.

PMID- 10199568
TI  - RNA-protein interactions in the human RNase MRP ribonucleoprotein complex.
AB  - The eukaryotic nucleolus contains a large number of small RNA molecules that, in
      the form of small nucleolar ribonucleoprotein complexes (snoRNPs), are involved
      in the processing and modification of pre-rRNA. One of the snoRNPs that has been
      shown to possess enzymatic activity is the RNase MRP. RNase MRP is an
      endoribonuclease involved in the formation of the 5' end of 5.8S rRNA. In this
      study the association of the hPop1 protein with the RNase MRP complex was
      investigated. The hPop1 protein seems not to be directly bound to the RNA
      component, but requires nt 1-86 and 116-176 of the MRP RNA to associate with the
      RNase MRP complex via protein-protein interactions. UV crosslinking followed by
      ribonuclease treatment and immunoprecipitation with anti-Th/To antibodies
      revealed three human proteins of about 20, 25, and 40 kDa that can associate with
      the RNase MRP complex. The 20- and 25-kDa proteins appear to bind to stem-loop I
      of the MRP RNA whereas the 40-kDa protein requires the central part of the MRP
      RNA (nt 86-176) for association with the RNase MRP complex. In addition, we show
      that the human RNase P proteins Rpp30 and Rpp38 are also associated with the
      RNase MRP complex. Expression of Vesicular Stomatitis Virus- (VSV) tagged
      versions of these proteins in HeLa cells followed by anti-VSV immunoprecipitation
      resulted in coprecipitation of both RNase P and RNase MRP complexes. Furthermore,
      UV crosslinking followed by anti-Th/To and anti-Rpp38 immunoprecipitation
      revealed that the 40-kDa protein we detected in UV crosslinking is probably
      identical to Rpp38.

PMID- 10199569
TI  - Conservation of functional features of U6atac and U12 snRNAs between vertebrates
      and higher plants.
AB  - Splicing of U12-dependent introns requires the function of U11, U12, U6atac,
      U4atac, and U5 snRNAs. Recent studies have suggested that U6atac and U12 snRNAs
      interact extensively with each other, as well as with the pre-mRNA by Watson
      Crick base pairing. The overall structure and many of the sequences are very
      similar to the highly conserved analogous regions of U6 and U2 snRNAs. We have
      identified the homologs of U6atac and U12 snRNAs in the plant Arabidopsis
      thaliana. These snRNAs are significantly diverged from human, showing overall
      identities of 65% for U6atac and 55% for U12 snRNA. However, there is almost
      complete conservation of the sequences and structures that are implicated in
      splicing. The sequence of plant U6atac snRNA shows complete conservation of the
      nucleotides that base pair to the 5' splice site sequences of U12-dependent
      introns in human. The immediately adjacent AGAGA sequence, which is found in
      human U6atac and all U6 snRNAs, is also conserved. High conservation is also
      observed in the sequences of U6atac and U12 that are believed to base pair with
      each other. The intramolecular U6atac stem-loop structure immediately adjacent to
      the U12 interaction region differs from the human sequence in 9 out of 21
      positions. Most of these differences are in base pairing regions with
      compensatory changes occurring across the stem. To show that this stem-loop was
      functional, it was transplanted into a human suppressor U6atac snRNA expression
      construct. This chimeric snRNA was inactive in vivo but could be rescued by
      coexpression of a U4atac snRNA expression construct containing compensatory
      mutations that restored base pairing to the chimeric U6atac snRNA. These data
      show that base pairing of U4atac snRNA to U6atac snRNA has a required role in
      vivo and that the plant U6atac intramolecular stem-loop is the functional analog
      of the human sequence.

PMID- 10199570
TI  - Coordination of tRNA nuclear export with processing of tRNA.
AB  - Eukaryotic tRNAs are synthesized in the nucleus and need to be exported to the
      cytoplasm where they function in translation. tRNA export is mediated by exportin
      t, which binds tRNA directly and with high affinity. tRNAs are initially
      synthesized as precursor molecules. Maturation to functional tRNA takes place in
      the nucleus, precedes export, and includes trimming of the 5' and 3' ends,
      posttranscriptional addition of the 3' CCA end, nucleoside modifications, and in
      some cases splicing. Here we address the question of how tRNA maturation is
      coordinated with export and thus how cytoplasmic accumulation of inactive
      maturation intermediates is avoided. This could, in principle, be achieved by
      nuclear retention of immature tRNA or by selective export of the fully mature
      form. We show that exportin-t has a strong preference for tRNA with correctly
      processed 5' and 3' ends and nucleoside modification. tRNA recognition by
      exportin-t can thus be considered as a quality control mechanism for these
      maturation steps prior to tRNA export. Surprisingly however, exportin-t can
      efficiently bind unspliced tRNA and intron-containing tRNA is exported when the
      rate of splicing is slow. During characterization of the exportin-t/tRNA
      interaction we found that exportin-t recognizes features in the tRNA that are
      conserved between prokaryotic and eukaryotic tRNAs. Our data suggest that correct
      tRNA shape, the 5' and 3' terminal ends, and the TpsiC loop are critical for
      exportin-t binding.

PMID- 10199571
TI  - Subgenomic mRNA regulation by a distal RNA element in a (+)-strand RNA virus.
AB  - Subgenomic (sg) mRNAs are synthesized by (+)-strand RNA viruses to allow for
      efficient translation of products encoded 3' in their genomes. This strategy also
      provides a means for regulating the expression of such products via modulation of
      sg mRNA accumulation. We have studied the mechanism by which sg mRNAs levels are
      controlled in tomato bushy stunt virus, a small (+)-strand RNA virus which
      synthesizes two sg mRNAs during infections. Neither the viral capsid nor movement
      proteins were found to play any significant role in modulating the accumulation
      levels of either sg mRNA. Deletion analysis did, however, identify a 12-nt-long
      RNA sequence located approximately 1,000 nt upstream from the site of initiation
      of sg mRNA2 synthesis that was required specifically for accumulation of sg
      mRNA2. Further analysis revealed a potential base-pairing interaction between
      this sequence and a sequence located just 5' to the site of initiation for sg
      mRNA2 synthesis. Mutant genomes in which this interaction was either disrupted or
      maintained were analyzed and the results indicated a positive correlation between
      the predicted stability of the base-pairing interaction and the efficiency of sg
      mRNA2 accumulation. The functional significance of the long-distance interaction
      was further supported by phylogenetic sequence analysis which revealed
      conservation of base-pairing interactions of similar stability and relative
      position in the genomes of different tombusviruses. It is proposed that the
      upstream sequence represents a cis-acting RNA element which facilitates sg mRNA
      accumulation by promoting efficient synthesis of sg mRNA2 via a long-distance RNA
      RNA interaction.

PMID- 10199572
TI  - Nonsense mutations in the alcohol dehydrogenase gene of Drosophila melanogaster
      correlate with an abnormal 3' end processing of the corresponding pre-mRNA.
AB  - From bacteria to mammals, mutations that generate premature termination codons
      have been shown to result in the reduction in the abundance of the corresponding
      mRNA. In mammalian cells, more often than not, the reduction happens while the
      RNA is still associated with the nucleus. Here, it is reported that mutations in
      the alcohol dehydrogenase gene (Adh) of Drosophila melanogaster that generate
      premature termination codons lead to reduced levels of cytoplasmic and nuclear
      mRNA. Unexpectedly, it has been found that the poly(A) tails of Adh mRNAs and pre
      mRNAs that carry a premature termination codon are longer than in the wild-type
      transcript. The more 5' terminal the mutation is, the longer is the poly(A) tail
      of the transcript. These findings suggest that the integrity of the coding region
      may be required for accurate mRNA 3' end processing.

PMID- 10199573
TI  - Formation of metastable RNA structures by sequential folding during
      transcription: time-resolved structural analysis of potato spindle tuber viroid (
      )-stranded RNA by temperature-gradient gel electrophoresis.
AB  - A model of functional elements critical for replication and infectivity of the
      potato spindle tuber viroid (PSTVd) was proposed earlier: a thermodynamically
      metastable structure containing a specific hairpin (HP II) in the (-)-strand
      replication intermediate is essential for template activity during (+)-strand
      synthesis. We present here a detailed kinetic analysis on how PSTVd (-)-strands
      fold during synthesis by sequential folding into a variety of metastable
      structures that rearrange only slowly into the structure distribution of the
      thermodynamic equilibrium. Synthesis of PSTVd (-)-strands was performed by T7-RNA
      polymerase; the rate of synthesis was varied by altering the concentration of
      nucleoside triphosphates to mimic the in vivo synthesis rate of DNA-dependent RNA
      polymerase II. With dependence on rate and duration of the synthesis, the
      structure distributions were analyzed by temperature-gradient gel electrophoresis
      (TGGE). Metastable structures are generated preferentially at low transcription
      rates--similar to in vivo rates--or at short transcription times at higher rates.
      Higher transcription rates or longer transcription times lead to metastable
      structures in low or undetectable amounts. Instead different structures do
      gradually appear having a more rod-like shape and higher thermodynamic stability,
      and the thermodynamically optimal rod-like structure dominates finally. It is
      concluded that viroids are able to use metastable as well as stable structures
      for their biological functions.

PMID- 10199574
TI  - UV-induced modifications in the peptidyl transferase loop of 23S rRNA dependent
      on binding of the streptogramin B antibiotic, pristinamycin IA.
AB  - The naturally occurring streptogramin B antibiotic, pristinamycin IA, which
      inhibits peptide elongation, can produce two modifications in 23S rRNA when bound
      to the Escherichia coli 70S ribosome and irradiated at 365 nm. Both drug-induced
      effects map to highly conserved nucleotides within the functionally important
      peptidyl transferase loop of 23S rRNA at positions m2A2503/psi2504 and
      G2061/A2062. The modification yields are influenced strongly, and differentially,
      by P-site-bound tRNA and strongly by some of the peptidyl transferase antibiotics
      tested, with chloramphenicol producing a shift in the latter modification to
      A2062/C2063. Pristinamycin IA can also produce a modification on binding to
      deproteinized, mature 23S rRNA, at position U2500/C2501. The same modification
      occurs on an approximately 37-nt fragment, encompassing positions approximately
      2496-2532 of the peptidyl transferase loop that was excised from the mature rRNA
      using RNAse H. In contrast, no antibiotic-induced effects were observed on in
      vitro T7 transcripts of full-length 23S rRNA, domain V, or on a fragment
      extending from positions approximately 2496-2566, which indicates that one or
      more posttranscriptional modifications within the sequence Cm-C-U-C-G-m2A-psi
      G2505 are important for pristinamycin IA binding and/or the antibiotic-dependent
      modification of 23S rRNA.

PMID- 10199575
TI  - Identification of RNAs that bind to a specific protein using the yeast three
      hybrid system.
AB  - We have adapted the yeast three-hybrid system to identify RNA ligands for an RNA
      binding protein. In this assay system, a protein-RNA interaction is detected by
      the reconstitution of a transcriptional activator using two hybrid proteins and a
      hybrid RNA. The RNA molecule is tethered to the promoter of a reporter gene by
      binding to a hybrid protein consisting of the bacteriophage MS2 coat protein
      fused to the DNA-binding protein LexA; the RNA-binding domain to be analyzed is
      fused to the transcriptional activation domain of the yeast Gal4 protein; and the
      bifunctional RNA consists of binding sites for the coat protein and for the other
      RNA-binding domain. We built an RNA library such that short fragments of genomic
      DNA from yeast were transcribed in yeast together with binding sites for the coat
      protein. We screened this hybrid RNA library for RNAs that bound to the yeast
      Snp1 protein, a homolog of the human U1-70K protein. The screen yielded as the
      strongest positive the fragment of U1 RNA that contains loop I, which is known to
      bind to Snp1 in U1 snRNP. We also identified four other RNA ligands that produced
      weaker three-hybrid signals, suggesting lower affinities for Snp1 as compared to
      U1 RNA. In addition, this search also yielded a set of RNA sequences that can
      activate transcription on their own when bound to a promoter through a protein
      interaction.

PMID- 10199576
TI  - Deltamethrin-induced testicular apoptosis in rats: the protective effect of
      nitric oxide synthase inhibitor.
AB  - This study is the first to examine and characterize the testicular apoptosis
      which might be induced due to exposure of male rats to deltamethrin. Furthermore,
      the role which might be played by nitric oxide (NO), as well as the other
      reactive oxygen species (ROS) in controlling this testicular apoptosis was
      assessed. Apoptosis was evaluated by DNA fragmentation detected by agarose gel
      electrophoresis and cellular morphology on testicular tissue sections. It was
      found that administration of deltamethrin (1 mg/kg daily for 21 days) to animals
      resulted in characteristic DNA migration patterns (laddering), thereby providing
      evidence that apoptosis is the major mechanism of cell death in the testicular
      tissues. In addition, histopathological examination of testicular tissue sections
      showed that apoptosis was confined to the basal germ cells, primary and secondary
      spermatocytes. These changes, in addition to the appearance of Sertoli cell
      vacuoles in deltamethrin-intoxicated animals, indicates the suppression of
      spermatogenesis. At the same time, the plasma levels of both NO and lipid
      peroxides measured as malondialdehyde (MDA) were found to be significantly
      increased in deltamethrin-treated animals. Administration of NO synthase (NOS)
      inhibitors such as N(G)-nitro monomethyl L-arginine hydrochloride (L-NMMA, 1
      mg/kg) to rats 2 h before exposure to deltamethrin was effective in the reduction
      of the typically testicular apoptotic DNA fragmentation pattern and the
      associated histopathological changes. These findings may suggest that
      deltamethrin-induced testicular apoptosis is mediated by NO. Therefore, the
      pharmacological manipulation of apoptosis by selective NOS inhibitors such as L
      NMMA may offer new possibilities for the control of deltamethrin-induced
      testicular dysfunction and infertility in the future.

PMID- 10199577
TI  - Trichloroethylene inhibits aldehyde dehydrogenase only for aliphatic aldehydes of
      short chains in rats.
AB  - The effects of trichloroethylene (TCE) administration on aldehyde dehydrogenase
      (ALDH) and cytochrome P450 isozymes were studied in rats and compared with those
      of methanol. Intragastric administration of TCE to rats at 0.05 or 0.2 ml/kg for
      1 week significantly inhibited ALDH activity for aliphatic aldehydes of short
      chains in the mitochondrial and cytosolic fractions of rat liver, respectively,
      but had no effect on the activity for long chain aliphatic aldehydes. ALDH
      activity catalyzing the metabolism of some aromatic aldehydes was even induced by
      TCE. Microsomal ALDH activity was not decreased by TCE treatment. A kinetic study
      showed that the low-Km isozyme of ALDH for propionaldehyde in mitochondrial and
      cytosolic fractions was inhibited by TCE treatment. Addition of TCE,
      trichloroethanol or trichloroacetic acid to the in vitro assay system did not
      affect the activity for acetaldehyde, but chloral hydrate at 0.02 mM decreased
      the activity by 42 and 35% in cytosol and the 700 x g supernatant, respectively.
      Methanol treatment, on the other hand, had no effect on any ALDH activity. Both
      TCE and methanol significantly induced CYP2E1 in rat liver. The combined effects
      of TCE on ALDH and cytochrome P450 may account for the degreasers' flush.
      Exposure to TCE and methanol may result in a change in the metabolism and
      toxicity of other chemicals.

PMID- 10199578
TI  - Pb2+ promotes lipid oxidation and alterations in membrane physical properties.
AB  - Experimental evidence suggests that cellular damage mediated by oxidants could be
      involved in the pathology associated with lead (Pb) toxicity. We investigated the
      effect of Pb2+ on lipid oxidation in liposomes using different initiators. In the
      presence of Fe2+, Pb2+ (12.5-200 microM) stimulated lipid oxidation in
      phosphatidylcholine:phosphatidylserine-containing liposomes, measured as 2
      thiobarbituric acid-reactive substances (TBARS) and conjugated dienes. This
      stimulatory effect depended on the presence of membrane negative charges and on
      bilayer integrity. Pb2+ did not stimulate TBARS formation in the presence of 25
      mM 2,2'-azo-bis (2,4 dimethylvaleronitrile (AMVN) and 2,2' azobis (2
      amidinopropane) (AAPH). Pb2+ significantly stimulated TBARS production and NADH
      oxidation in the presence of photoactivated rose Bengal. The use of specific
      inhibitors indicated that several reactive oxygen species were involved in the
      pro-oxidant action of Pb2+. Pb2+ (12.5-200 microM) caused membrane lateral phase
      separation and this effect was positively correlated with its capacity to
      stimulate Fe2+ and rose Bengal-initiated TBARS production. Pb2+ could bind to the
      membrane and act to stimulate lipid oxidation by causing changes in membrane
      physical properties. Through this mechanism Pb2+ would favor the propagation of
      lipid oxidation. By causing lateral phase separation and/or by increasing lipid
      oxidation rates, Pb2+ could be cytotoxic by altering membrane-related processes.

PMID- 10199579
TI  - Metallothionein does not protect mouse endocrine cells from damage induced by
      alloxan injection.
AB  - Effects of metallothionein (MT) on pancreatic endocrine cells of mice, injected
      with alloxan and at different zinc status were studied. Mice were given drinking
      water containing four different concentrations of zinc (0, 0.05, 0.1 or 0.5%) for
      18 days, and alloxan was injected once on the 14th day. When zinc was added to
      the drinking water, pancreatic zinc and MT contents increased after injection of
      alloxan, but did not change with injection of vehicle alone, except in the group
      of mice drinking 0.5% zinc in water. However, plasma glucose level was increased
      in all the alloxan injected groups, and was independent of their zinc status. In
      mice given water with 0.5% of zinc, both pancreatic zinc and MT contents were
      higher than control mice given water alone. There was no difference in zinc and
      MT contents of the pancreas in mice drinking 0.5% zinc in groups injected with
      either alloxan or vehicle. The increase in plasma alpha-amylase activity, an
      indicator of pancreatic exocrine toxicity, was observed only in mice drinking
      water with 0.5% zinc after injection of both alloxan and vehicle.
      Histochemically, degranulation of zymogen and duct-like structures of exocrine
      cells and atrophy and disappearance of islet cells were observed in alloxan
      injected mice drinking 0.5% zinc in water. The zymogen degranulation was observed
      on the vehicle-injected mice drinking 0.5% zinc in water. MT was
      immunohistochemically detected in the exocrine cells of both alloxan- and vehicle
      injected mice given 0.5% zinc in water. No MT was detected in islet cells of mice
      in any group. The results show that an increase of zinc content may be followed
      by induction of MT synthesis in the pancreas of mice given increasing amounts of
      zinc in drinking water. However, MT dose not provide any protection against
      damage caused by alloxan to endocrine cells of the pancreas.

PMID- 10199580
TI  - Effect of glucuronidation substrates/inhibitors on N-(3,5
      dichlorophenyl)succinimide nephrotoxicity in Fischer 344 rats.
AB  - The agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) is an acute
      nephrotoxicant in rats. Our previous studies have strongly suggested that
      glucuronide conjugation of NDPS metabolites might be a bioactivation step
      mediating NDPS nephrotoxicity. In this study, effects of substrates and/or
      inhibitors of primarily glucuronidation on NDPS nephrotoxicity were examined to
      explore further the role of glucuronidation in NDPS nephrotoxicity. Male Fischer
      344 rats (4-6/group) were administered one of the following intraperitoneal
      (i.p.) pretreatments (dose, pretreatment time) prior to NDPS (0.4 mmol/kg) or
      NDPS vehicle (sesame oil, 2.5 ml/kg): (1) no pretreatment; (2) borneol (900
      mg/kg, 30 min); (3) eugenol (500 mg/kg per day, 3 days); (4) clofibric acid (400
      mg/kg, 15 min before (1/2 dose) and 3 h after (1/2 dose)), or (5) valproic acid,
      sodium salt (1.0 mmol/kg, 15 min). Following NDPS or NDPS vehicle administration,
      renal function was monitored at 24 and 48 h. Pretreatment with borneol or
      eugenol, substrates for ether glucuronidation and sulfation (mainly
      glucuronidation), afforded complete protection against NDPS nephrotoxicity.
      Substrates for acyl glucuronidation, clofibric acid or valproic acid, mildly
      reduced or had little effect on NDPS nephrotoxicity, respectively. These results
      suggest that ether glucuronide conjugates of NDPS metabolites, rather than acyl
      glucuronide conjugates, may be the primary ultimate nephrotoxicant species
      mediating NDPS nephrotoxicity.

PMID- 10199581
TI  - Analysis of interleukin 12 protein production and mRNA expression in mice exposed
      topically to chemical allergens.
AB  - Interleukin (IL) 12 is a heterodimeric cytokine which stimulates IFN-gamma
      production and promotes the development of type 1 T helper cells and T cytotoxic
      cells from their respective precursors. We have described previously that contact
      allergens such as 2,4-dinitrochlorobenzene (DNCB), and respiratory allergens such
      as trimellitic anhydride (TMA) induce discrete type 1 and type 2 cytokine
      secretion patterns, respectively, following repeated topical exposure of BALB/c
      strain mice. Under such conditions, we have now examined production by draining
      LNC of the inducible subunit of IL-12 (p40) and p40 and p35 subunit mRNA
      expression. Cultured LNC prepared from mice treated with DNCB secreted
      significantly more IL-12 p40 protein than did TMA- or vehicle-activated LNC, such
      differences becoming more pronounced as the duration of culture increased.
      Maximal levels of mRNA expression of the IL-12 p40 subunit were observed after 6
      24 h of culture in all treatment groups and declined thereafter. Somewhat higher
      levels were induced following exposure to DNCB, these differences only reached
      statistical significance at 24 h of culture. Expression of this subunit by LNC
      from all treatment groups declined with time in culture. Levels of IL-12 p35 mRNA
      expression were comparable in cultured LNC prepared from allergen and vehicle
      treated mice and remained constant throughout the entire culture period. These
      data indicate that the divergent T cell cytokine responses seen in response to
      contact and respiratory allergens are associated with differential production of
      IL-12 p40 protein in the absence of substantial changes in the expression of mRNA
      for either subunit.

PMID- 10199582
TI  - Persistent effect of in utero meso-2,3-dimercaptosuccinic acid (DMSA) on immune
      function and lead-induced immunotoxicity.
AB  - Meso-2,3-dimercaptosuccinic acid (DMSA) is a drug currently employed for cheltion
      therapy in lead poisoning; however, little is known about its potential effects
      on the immune system. To examine the effect of DMSA and its capacity to reverse
      immunotoxicity resulting from exposure to lead in utero, female Fischer 344 rats
      were administered lead acetate in drinking water from 2 weeks prior to mating
      until parturition; DMSA was given by gavage on days 6-21 of gestation. The immune
      function of the female offspring was tested at 13 weeks of age. The results
      showed that lead (250 ppm) suppressed Th1-type responses (delayed-type
      hypersensitivity (DTH), interferon gamma (IFN gamma) production), enhanced a Th2
      type response (interleukin-4 (IL-4) production), and increased tumor necrosis
      factor alpha (TNF alpha) production from macrophages. DMSA treatment (60 mg/kg
      per day) during pregnancy significantly lowered the blood lead levels of both the
      embryos and the lactating dams as well as the milk lead level of lactating dams.
      The chelation treatment also reversed the lead-induced alterations in pup body
      weight, relative spleen weight, TNF alpha, and IL-4 production. But in utero
      exposure to DMSA alone resulted in decreased DTH response in adult offspring.
      This was likely due to a reduced cell recruitment, since plasma monocyte
      chemoattractant protein-1 (MCP-1) levels were decreased. The DMSA-exposed
      offspring also demonstrated increased interleukin-2 (IL-2) production. These
      results suggest that DMSA reverses some of the lead-induced immunotoxicity;
      however, this treatment itself during embryonic development produces subsequent
      adult immunomodulation.

PMID- 10199584
TI  - Acute and chronic oral administration of bis(maltolato)oxovanadium(IV) in Zucker
      diabetic fatty (ZDF) rats.
AB  - This is a preliminary study in which both acute and chronic oral administration
      of bis(maltolato)oxovanadium (IV) (BMOV) was examined in the Zucker diabetic
      fatty (ZDF) rat, an animal model that develops overt hyperglycemia in the
      presence of hyperinsulinemia followed by beta-cell depletion. At 9-10 weeks of
      age, in the presence of hyperglycemia, hyperinsulinemia and hyperlipidemia, an
      acute oral gavage dose response was conducted to determine glucose-lowering
      properties of BMOV, time of response and effect of BMOV on plasma insulin levels.
      Doses of BMOV greater than 0.2 mmol/kg resulted in plasma glucose levels of less
      than 9 mmol/l. The highest dose administered (0.8 mmol/kg) significantly reduced
      plasma insulin (initial: 2.83+/-0.2, final: 1.23+/-0.09 nmol/l, P<0.05) and
      plasma triglyceride (initial: 4.94+/-0.33, final: 1.55+/-0.07 mmol/l, P<0.05)
      levels. At 15 weeks of age, in the presence of hyperglycemia, hyperlipidemia and
      normal insulin levels, BMOV was administered orally in the drinking water for a
      10-week period to determine the effect of treatment on glucose, insulin and lipid
      levels. BMOV treatment significantly reduced plasma glucose levels (final BMOV
      treated: 13.25+/-1.43, untreated: 28.71+/-0.6 mmol/l, P<0.05) and effectively
      preserved pancreatic beta-cell function. These data suggest a role for BMOV as a
      therapeutic agent in non-insulin-dependent diabetes mellitus through improvement
      in glucose homeostasis and preservation of insulin reserves.

PMID- 10199583
TI  - Inhibition of aldose reductase in human erythrocytes by vitamin C.
AB  - Ascorbic acid, or vitamin C, has been reported to lower erythrocyte sorbitol
      concentrations, and present studies were performed to determine the mechanism of
      this effect. Incubation of erythrocytes with increasing concentrations of glucose
      (5-40 mM) progressively increased erythrocyte sorbitol contents, reflecting
      increased flux through aldose reductase. At extracellular concentrations of 90
      microM, both ascorbic acid and its oxidized form, dehydroascorbate, decreased
      intracellular sorbitol by 25 and 45%, respectively. This inhibition was not
      dependent on the extracellular glucose concentration, or on erythrocyte contents
      of free NADPH or GSH. To test for a direct effect of ascorbate on aldose
      reductase, erythrocyte hemolysates were prepared and supplemented with 100 microM
      NADPH. Hemolysates reduced glucose to sorbitol in a dose-dependent manner that
      was inhibited with a Ki of 120 microM by the aldose reductase inhibitor
      tetramethylene glutaric acid. Above 100 microM, ascorbic acid also lowered
      hemolysate sorbitol generation by about 30%. Studies with ascorbic acid
      derivatives showed that the reducing capacity of ascorbic acid was not required
      for inhibition of sorbitol production from glucose in erythrocyte hemolysates.
      These results show that high, but physiologic, concentrations of ascorbic acid
      can directly inhibit erythrocyte aldose reductase, and provide a rationale for
      the use of oral vitamin C supplements in diabetes.

PMID- 10199585
TI  - Potentiating effects of hyper-osmolality and epidermal growth factor on the
      release of arachidonic acid in human glomerular mesangial cells.
AB  - Studies were performed to determine the interactive effects of high
      concentrations of glucose (HG) and epidermal growth factor (EGF) on the release
      of arachidonic acid (3H-AA) in human glomerular mesangial cells (MC) in culture.
      Since high glucose has been reported to increase the mass of diacylglycerol (DAG)
      in MC, the HG-induced release of 3H-AA was compared to that initiated by the
      phorbol ester, PMA. It was found that when media contained high levels (25 mM) of
      glucose, the release of 3H-AA was increased significantly by 8.4% (change from
      control) after 1 h of exposure and was maintained at values not significantly
      different from this level for the next 2 h. After 3-h exposure, there was no
      significant difference between 25 and 50 mM glucose, suggesting that the effects
      of glucose are saturating at 25 mM. After 1-h exposure, 3H-AA release was also
      increased by PMA; however, the increase was larger and the peak increase was
      delayed until after 1 h. 3H-AA release was significantly increased by epidermal
      growth factor (EGF) by 8.5% after 1 h and was maintained at this level after 2
      and 3 h of exposure. In the presence of HG, EGF increased 3H-AA release by 24.6%
      after the 1st hour and by 20.4 and 19.4%, after the 2nd and 3rd hours,
      respectively. Mannitol (20 mM), added as an osmotic control, increased 3H-AA
      release by 6.2% and also significantly enhanced the effects of EGF after 3 h. The
      experimental values (19.0%) for the release of 3H-AA after 3-h exposure to EGF in
      combination with either high glucose or mannitol were significantly greater than
      the expected (added) values (12.1%). These results demonstrate that as a result
      of an elevated solution osmolality, high glucose acts synergistically with EGF to
      increase the release of 3H-AA in human mesangial cells.

PMID- 10199586
TI  - Prevalence of diabetes in Catalonia (Spain): an oral glucose tolerance test-based
      population study.
AB  - The goal of this study was to investigate the prevalence of diabetes mellitus and
      impaired glucose tolerance in the adult population of Catalonia and study their
      association with obesity, central obesity, hypertension and smoking habit. A
      random sample of 3839 subjects aged 30-89 years participated in this cross
      sectional study: 2214 subjects underwent a health examination with oral glucose
      tolerance test (OGTT) and 1625 were interviewed by phone. Diabetes prevalence
      (known and unknown) in the 30-89-year-old population was 10.3%, (95% CI: 9.1
      11.6). In this age group, the prevalence rates of known diabetes, unknown
      diabetes and impaired glucose tolerance were 6.4, 3.9 and 11.9% in men and 6.9,
      3.4 and 11.9% in women. The age adjusted prevalence to the world population for
      the 30-64-year-old age group was 6.1% (7.1% in men and 5.2% in women).The factors
      significantly associated with diabetes were age, obesity, hypertension and family
      history of diabetes. The high ratio of previously known diabetic cases to newly
      discovered ones, specially in the oldest age group, suggests good levels of
      awareness and medical services. The prevalence in Catalonia is similar to that
      observed in other Mediterranean countries.

PMID- 10199587
TI  - Temporal trends in spontaneous abortion associated with Type 1 diabetes.
AB  - The objective of this study was to investigate temporal changes in the reported
      rates of spontaneous abortion associated with Type 1 diabetes. Individuals from
      the Children's Hospital of Pittsburgh Type 1 Diabetes Registry for 1950-1964
      (n=495) completed a self-report reproductive history questionnaire in 1981 that
      was updated in 1990. Data from both surveys, which proved to be valid and
      reliable, were utilized for this report. More spontaneous abortions (26.8 vs.
      7.7%, P<0.001), stillbirths (4.7 vs. 1.2%, P<0.001) and induced abortions (7.0
      vs. 0.9%, P<0.001) were reported for Type 1 diabetic women than for the non
      diabetic partners of Type 1 diabetic men. A significant temporal decline in the
      rates of spontaneous abortion for Type 1 diabetic women was observed (< or =
      1969: 26.4%; 1970-1979: 31.0%; 1980-1989: 15.7%; P<0.05). No differences were
      apparent for the non-diabetic partners of Type 1 diabetic men (< or = 1969: 4.2%;
      1970-1979: 9.5%; 1980-1989: 5.7%; P>0.05). Temporal changes in medical care for
      women with diabetes (i.e. self-monitoring of glycemic control) may have
      contributed to a recent reduction in spontaneous abortions associated with
      maternal Type 1 diabetes.

PMID- 10199588
TI  - Preperitoneal fat deposition estimated by ultrasonography in patients with non
      insulin-dependent diabetes mellitus.
AB  - Preperitoneal fat is an indicator of visceral fat deposition, which is closely
      related to atherosclerosis and coronary heart disease in obese patients. We
      assessed the relationship of preperitoneal fat deposition and various clinical
      characteristics in 90 patients with non-insulin-dependent diabetes mellitus
      (NIDDM). Preperitoneal and subcutaneous fat deposition were measured by
      ultrasonography. In both the male and female diabetics, preperitoneal fat levels
      were significantly higher than in age-matched healthy subjects. We also
      determined blood pressures, fasting plasma glucose, glycosylated hemoglobin A1c,
      serum lipids, fasting immunoreactive insulin (FIRI), daily urinary C-peptide
      (CPR), serum leptin, urinary albumin excretion and body mass index (BMI). Of
      these parameters, BMI, FIRI, leptin and daily urinary CPR were positively
      correlated with preperitoneal fat deposition. Patients with diet therapy alone
      showed significantly higher preperitoneal fat levels than those receiving insulin
      therapy. In female, patients with increased preperitoneal fat showed higher
      prevalence of hypertension than those with decreased fat. Macroalbuminuric
      patients had a lower preperitoneal fat than microalbuminuric and normoalbuminuric
      patients. Patients with proliferative retinopathy exhibited lower preperitoneal
      fat than did those without retinopathy. Preperitoneal fat levels were positively
      correlated with motor or sensory nerve conduction velocity. CONCLUSION: The
      present findings suggest that in NIDDM patients, increased preperitoneal fat
      deposition is closely associated with obesity, hypertension and hyperinsulinemia,
      and negatively modulates diabetic microangiopathy including nephropathy,
      retinopathy and neuropathy.

PMID- 10199589
TI  - Prevalence of glutamic acid decarboxylase antibodies amongst young Malaysian
      diabetics.
AB  - This study determined the prevalence of glutamic acid decarboxylase antibodies
      (GAD Ab) in a group of 926 young Malaysian diabetics of three ethnic groups,
      Malay, Chinese, and Indian. Patients were clinically diagnosed to be Type 1 or
      Type 2 before the age of 40 years. The overall GAD Ab positivity was 17.4%
      (161/926), significantly higher in the Type 1 than the Type 2 diabetics (35.5%,
      116/329 vs. 7.5%, 45/597, P=0.0001). Compared to GAD Ab negative patients,
      seropositive diabetics were diagnosed at younger age (21.2+/-0.9 vs. 27.4+/-0.3
      y, P=0.0001), had lower fasting (289+/-27.4 vs. 640+/-17.6 pmol/l, P=0.0001) and
      post-glucagon C-peptide levels (527+/-51.8 vs. 1030+/-28.9 pmol/l, P=0.0001).
      There were no racial differences in the prevalence of GAD Ab; of the total Type
      1, 30.8, 36.4, and 39.4% were Malay, Chinese, and Indian diabetics, respectively
      and of the total Type 2, 8.8, 8.2, and 4.4% were Malay, Chinese, and Indian
      diabetics respectively. There was a curvilinear relationship between GAD Ab and
      the post-glucagon C-peptide levels, suggesting that GAD Ab do play a role in the
      beta-cells destruction and could be an important immune marker for the LADA
      group. This study reconfirmed previous reports that the autoimmune mechanisms in
      the Type 1 Asian diabetics are indeed different from the Caucasians, and further
      investigations should be carried out to explain the differences.

PMID- 10199590
TI  - Mortality in diabetes mellitus--data from a developing region of the world.
AB  - This retrospective study presents the mortality trends in diabetic patients in a
      developing region of the world. The data were collected by screening the hospital
      records of all diabetic patients who died over a period of a decade at Institute
      of Medical Sciences, a tertiary care medical centre in Kashmir Valley of India.
      Of 133,374 patients admitted to the centre from January 1987 to December 1996,
      9627 died, of whom 269 (151 males and 118 females) were recorded to have diabetes
      mellitus. The mean+/-S.D. age at the time of death was 51.61+/-13.77 years for
      males and 51.50+/-15.50 years for females. The common causes contributing to
      death were infections (33.83%), chronic renal failure (30.85%), coronary artery
      disease (16.36%), cerebrovascular disease (13.75%), hypoglycaemia (7.81%),
      diabetic ketoacidosis (6.69%) and hyperosmolar coma (2.23%). In 7.43% patients
      the cause of death could not be ascertained. Death was attributed to single cause
      in 60.22%, to two causes in 26.39% and to three or more causes in 5.95%. Most
      (59.11%) of these diabetic patients died within a week of hospitalisation. We
      conclude that mortality trends in diabetes mellitus differ in developing regions
      as compared to developed regions reflecting poor healthcare in general and
      diabetic care in particular. Unlike in west, where the major killers in diabetic
      patients are coronary artery disease and cerebrovascular disease, infections and
      chronic renal failure continue to be leading causes of death in patients with
      diabetes mellitus in developing regions like ours.

PMID- 10199591
TI  - Effect of diet and nutrition on the expression of cytochromes P450.

PMID- 10199592
TI  - Glutathione S-transferases in wild-type and doxorubicin-resistant MCF-7 human
      breast cancer cell lines.
AB  - 1. Overexpression of glutathione S-transferases (GST) in breast cancer cells is
      hypothesized to be a component of the multifactorial doxorubicin-resistant
      phenotype. 2. We have characterized the expression of GST enzymes at the
      catalytic activity, protein and mRNA levels in wild-type MCF-7 (MCF-7/WT) human
      breast cancer cells and a line selected for resistance to doxorubicin (MCF
      7/ADR), with the goal of modulating GST activity to overcome resistance. 3. The
      MCF-7/ADR cells were 30-65-fold more resistant to doxorubicin than the MCF-7/WT
      cells. 4. Total cytosolic GST catalytic activity was elevated 23-fold in the MCF
      7/ADR cells as compared with the MCF-7/WT cells, and the MCF-7/ADR cells also
      showed 3-fold increases in catalytic activity toward GST mu and alpha class
      selective substrates. Neither cell line showed detectable catalytic activity with
      a GST mu class-selective substrate. 5. MCF-7/ADR cells showed pronounced
      overexpression of GST mu protein and GST P1 mRNA in comparison with the wild-type
      cell line. Neither cell line displayed detectable GST alpha or mu at the protein
      level. 6. A glutathione analogue that functions as a selective GST alpha
      inhibitor was more potent at inhibiting total cytosolic GST catalytic activity in
      the MCF-7/ADR cell line than GST alpha and mu class-selective inhibitory
      glutathione analogues and the non-selective GST inhibitor ethacrynic acid. 7. The
      multidrug resistance-associated protein, which can function as a glutathione
      conjugate transporter, appeared weakly overexpressed in the MCF-7/ADR cells in
      comparison with the MCF-7/WT cells.

PMID- 10199593
TI  - Metabolism of digoxin and digoxigenin digitoxosides in rat liver microsomes:
      involvement of cytochrome P4503A.
AB  - 1. The sequential metabolism of digoxin (Dg3) to digoxigenin bis-digitoxoside
      (Dg2), digoxigenin mono-digitoxoside (Dg1) and digoxigenin (Dg0) was investigated
      in rat liver microsomes. 2. Kinetic studies produced results consistent with a
      single enzyme mechanism describing the successive oxidative cleavages. Formation
      of Dg2 was catalysed with mean (+/-SD) Km and Vmax of 125 +/- 22 microM and 362
      +/- 37 pmol/min/mg protein, respectively. The corresponding values for the
      formation of Dg1 were 61 +/- 5 microM and 7 +/-1 pmol/min/mg protein. Dg0
      formation was catalysed with the apparent values of 30 +/- 9 microM and 310 +/-
      30 pmol/min/mg protein. 3. Chemical inhibition of cytochrome P450 (CYP) 3A
      subfamily with ketoconazole and triacetyoleandomycin decreased the formation of
      Dg2 and Dg1 by up to 90%. Antibodies specific to rat CYP3A2 lowered the rate of
      oxidative cleavage of Dg3 and Dg2 by up to 85%. Inhibition of CYP2E1, CYP2C
      subfamily and CYP1A2 by chemical and immuno-inhibition did not affect initial
      rates of metabolism of Dg3 and Dg2. In contrast, Dg1 metabolism was not affected
      by triacetyloleandomycin as well as by antibodies to CYP3A2, CYP2C11, CYP2E1,
      CYP2B1/2B2 and CYP1A2. It was however inhibited by >80% by gestodene and 17alpha
      ethynylestradiol (selective inhibitors of human CYP3A). 4. Collectively, these
      data support the involvement of CYP3A in the cleavage of Dg3 and Dg2 in rat liver
      microsomes. The enzyme-metabolizing Dg1 remains to be identified.

PMID- 10199594
TI  - Contribution of human hepatic cytochrome P450s and steroidogenic CYP17 to the N
      demethylation of aminopyrine.
AB  - 1. Aminopyrine N-demethylase activity was determined for 11 forms of human
      hepatic cytochrome P450s (P450s) expressed in yeast Saccharomyces cerevisiae and
      for human steroidogenic CYP17 expressed in Escherichia coli. 2. Among the hepatic
      P450s, the N-demethylation of aminopyrine was catalysed most efficiently by
      CYP2C19, followed by CYP2C8, 2D6, 2C18 and 1A2, whereas the activity with CYP2E1
      was negligible. The kinetics of the N-demethylation process by CYP1A2, 2C8, 2C19
      and 2D6 were studied by fitting to Michaelis-Menten kinetics by Lineweaver-Burk
      plots. CYP2C19 exhibited the highest affinity and a high capacity for the
      aminopyrine N-demethylation. CYP2C8 showed the highest Vmax, followed by CYP2C19,
      2D6 and 1A2, whereas the Km for CYP2C8, 2D6 and 1A2 were 10-17 times higher than
      that for CYP2C19. Accordingly, the Vmax/Km for CYP2C19 was more than nine times
      higher than that of other P450s. 3. Human steroidogenic CYP17 also catalysed
      aminopyrine N-demethylation and the activity was comparable with that for CYP3A4
      which is a dominant P450 in human liver. The activity was increased 1.5-fold by
      the addition of cytochrome b5, whereas the activity was not affected by the
      addition of Mg2+. 4. These results suggest that several human hepatic P450s,
      especially CYP2C19, and steroidogenic CYP17 exhibit aminopyrine N-demethylase
      activity.

PMID- 10199595
TI  - Quantitative in vivo and in vitro sex differences in artemisinin metabolism in
      rat.
AB  - 1. The pharmacokinetics of the antimalarial compound artemisinin were compared in
      the male and female Sprague-Dawley rat after single dose i.v. (20 mg x kg(-1)) or
      i.p. (50 mg x kg(-1)) administration of an emulsion formulation. 2. Plasma
      clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) 1 x h(-1)
      x kg(-1) in the male rat and 10.6 (95% CI: 7.5, 15.0) 1 x h(-1) x kg(-1) in the
      female rat suggesting high hepatic extraction in combination with erythrocyte
      uptake or clearance. Artemisinin half-life was approximately 0.5 h after both
      routes of administration in both sexes. Values for plasma clearance and half
      lives did not statistically differ between the sexes. 3. After i.p.
      administration artemisinin AUCs were 2-fold higher in the female compared with
      male rat (p < 0.001). Artemisinin disappearance was 3.9-fold greater in
      microsomes from male compared with female livers and it was inhibited in male
      microsomes by goat or rabbit serum containing antibodies against CYP2C11 and
      CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma
      was lower (p < 0.001) in plasma obtained from the male (8.8 +/- 2.0%) compared
      with the female rat (11.7 +/- 2.2%). 5. The possibility of a marked sex
      difference, dependent on the route of administration, has to be taken into
      account in the design and interpretation of toxicological studies of artemisinin
      in this species.

PMID- 10199597
TI  - Synchronized approximately 15.0-35.0 Hz oscillatory response to spatially
      modulated visual patterns in man.
AB  - When suitably stimulated, neurons in the striate visual cortex of cats fire in
      bursts at 20-60 Hz and the membrane potential oscillates rhythmically in the same
      frequency range and in phase. These oscillations reflect intrinsic properties of
      mammalian neurons, occur in coherent spatial patterns that depend on the
      segregation and stimulus selectivity of stimulated cells, and mediate in long
      range synchronization across columns and over large cortical areas of cells
      responding to the same stimulus property/properties. The pool of activated
      neurons may be adequate in size to drive cellular oscillations into local fields
      and mass responses. Accordingly, stimulus-dependent oscillatory activity in the
      same frequency range was described in man after contrast stimulation. Our results
      describe oscillatory potentials at approximately 15.0-35.0 Hz that in man are
      (partly) independent from, and anticipate the occurrence of, the conventional low
      frequency visual response evoked by transient, foveal stimulation with spatially
      modulated patterns.

PMID- 10199596
TI  - Studies on the metabolism of 4-fluoroaniline and 4-fluoroacetanilide in rat:
      formation of 4-acetamidophenol (paracetamol) and its metabolites via
      defluorination and N-acetylation.
AB  - 1. The urinary metabolic fate of 4-fluoroaniline (4-FA) and 1-[13C]-4
      fluoroacetanilide (4-FAA) has been studied using NMR-based methods after 50 and
      100 mg kg(-1) i.p. doses respectively to the male Sprague-Dawley rat. 2. 4-FA was
      both ortho- and para-hydroxylated. The major metabolite produced by ortho
      hydroxylation was 2-amino-5-fluorophenylsulphate accounting for approximately 30%
      of the dose. Of the dose, approximately 10% was excreted via para-hydroxylation
      and the resulting defluorinated metabolites were N-acetylated and excreted as
      sulphate (major), glucuronide (minor) and N-acetyl-cysteinyl (minor) conjugates
      of 4-acetamidophenol (paracetamol). 3. The major route of metabolism of 1-[13C]-4
      FAA was N-deacetylation and the metabolites excreted in the urine were
      qualitatively identical to 4-FA. The paracetamol metabolites produced via para
      hydroxylation were also a product of N-deacetylation and reacetylation, as the
      [13C]-label was not retained. 4. These studies demonstrate the value of [13C]
      labelling in understanding the contribution of N-acetylation, and futile
      deacetylation-reacetylation reactions, in aniline metabolism. In addition, this
      work sheds new light on the metabolic lability of certain aromatic fluorine
      substituents.

PMID- 10199598
TI  - Long-term depression of perforant path excitatory postsynaptic potentials
      following synchronous network bursting in area CA3 of immature hippocampus.
AB  - Various forms of synaptic long-term potentiation and depression have been studied
      in detail in hippocampus and neocortex. Each are produced by specific patterns of
      synaptic activation and rely on electrical stimulation of afferents for their
      induction. Few studies have explored the ability of activity produced by cortical
      networks themselves to generate similar long-term changes in synaptic efficacy.
      Experiments have shown that periods of synchronized network bursting in both
      slices and dissociated cultures of hippocampus can lead to persistent network
      discharges. Conversely, one study has reported that network discharging can
      disrupt the induction of long-term potentiation in hippocampus. Whether long-term
      depression can be induced by synchronous network discharging is unknown. In
      experiments reported here, we examined the long-term effects of synchronized
      activity within hippocampal CA3 networks on synaptic potentials produced by the
      converging perforant path. Prior to induction of network bursting, slices were
      incubated in a perfusate containing picrotoxin and elevated (4 mM) Ca2+ and Mg2+.
      To induce network discharges, the concentration of both divalent cations were
      reduced to normal levels (1.5 mM). Following 20 min of network bursting,
      perforant path synapses, that did not participate in network discharging,
      underwent a 30% non-decrementing long-term depression. At the same time,
      synchronized network discharges, that were absent prior to induction, persisted
      upon return to preinduction conditions. The antagonist of the N-methyl-D
      aspartate receptor, D(-)2-amino-5-phosphonovalerate, blocked both long-term
      depression of perforant path excitatory postsynaptic potentials and persistent
      network discharging. Results suggest that activity generated by hippocampal
      networks is able to produce long-term depression of non-coincidentally active
      synapses.

PMID- 10199600
TI  - Differential responsiveness of dopamine transmission to food-stimuli in nucleus
      accumbens shell/core compartments.
AB  - The nucleus accumbens septi is the major target of mesolimbic dopamine neurons
      originating in the ventral tegmental area of the mesencephalon. Studies involving
      experimental manipulation of dopamine transmission by drugs and by lesions, as
      well as in vivo monitoring of extracellular dopamine concentrations, have
      provided evidence that the dopamine transmission of the nucleus accumbens plays
      an important role in behaviour motivated by conventional (e.g., food, sex) and
      drug reinforcers. Motivated behaviour is distinguished into an appetitive
      (preparatory/anticipatory) phase consisting of flexible response patterns
      intended to search and approach the reward itself, and a consummatory phase,
      consisting of fixed response patterns (eating, drinking, copulating, etc.)
      finalized to the utilization of the biological resources of the reward (caloric,
      metabolic, genetic, etc.). While some studies reported a stimulation of dopamine
      transmission in the nucleus accumbens in relation to appetitive as well as
      consummatory behaviour, other studies reported a relationship exclusively with
      consummatory behaviour. Therefore, the precise relationship between dopamine
      transmission in the nucleus accumbens and specific phases of motivated behaviour
      is debated. On the basis of topographical, histochemical and connectional
      evidence, the nucleus accumbens has been subdivided into two compartments, a
      medioventral "shell" and a laterodorsal "core". This heterogeneity may be
      relevant to the current debate over the role of nucleus accumbens dopamine in
      behaviour. Thus, one might hypothesize that, depending on the specific
      compartment of the nucleus accumbens where dopamine transmission is monitored, a
      different relationship with specific stimuli which motivate behaviour is
      obtained. In order to verify this possibility we monitored by microdialysis the
      changes in dopamine transmission in the nucleus accumbens shell and core during
      appetitive and consummatory phases of behaviour motivated by food. As food we
      utilized a palatable snack food (Fonzies) whose consumption has been shown in
      previous studies from our laboratory to release dopamine in the nucleus accumbens
      shell and in the medial prefrontal cortex. Unpredicted consumption of Fonzies
      preferentially stimulated dopamine transmission in the shell as compared to the
      core. Appetitive food stimuli (perforated Fonzies-filled boxes) phasically
      stimulated dopamine transmission in the core but not in the shell and sensitized
      the dopamine response to feeding in the core but inhibited that in the shell.
      These clear-cut differences between nucleus accumbens shell and core suggest that
      phasic dopamine transmission in each compartment of the nucleus accumbens
      subserves different roles in motivated behaviour.

PMID- 10199599
TI  - Opiate tolerance to daily heroin administration: an apparent phenomenon
      associated with enhanced pain sensitivity.
AB  - From a classical viewpoint, tolerance to analgesic effects of opiates refers to
      the decreased effectiveness of a given opiate following its repeated use. Despite
      much research, it has not been conclusively demonstrated in vivo that functional
      changes observed at the opioid receptor level in the responsiveness to opiates
      account for development of tolerance. An alternative hypothesis is that opioid
      receptors remain operative following repeated opiate administration but that
      opioid receptor activation rapidly induces a prolonged increase in pain
      sensitivity which opposes the predominant opiate analgesic effect following
      repeated opiate administration. We recently showed that a single heroin
      administration induces an enhanced pain sensitivity for several days, a
      phenomenon which is prevented by the non-competitive N-methyl-D aspartate
      receptor antagonist MK-801. Herein we report that repeated once-daily heroin
      injections induced a gradual lowering of the nociceptive threshold which
      progressively masked a sustained heroin analgesic functional effect. MK-801
      prevented such opiate-induced allodynia and thereby prevented development of an
      apparent decrease in the effectiveness of heroin. These results indicate that
      intermittent heroin administration induced a persistent increase in the basal
      pain sensitivity which, if not taken into account gives the impression of less
      analgesia, i.e. apparent tolerance.

PMID- 10199601
TI  - Glial cell line-derived neurotrophic factor protects against delayed neuronal
      death after transient forebrain ischemia in rats.
AB  - Glial cell line-derived neurotrophic factor, a member of the transforming growth
      factor-beta superfamily, is a potent neurotrophic factor, which has a variety of
      biological activities that affect several types of neurons in both the central
      and peripheral nervous systems. In this study, we examined the effects of glial
      cell line-derived neurotrophic factor on delayed neuronal death in the
      hippocampal CA1 region of rats after transient forebrain ischemia. In the control
      rats pretreated with the vehicle, transient forebrain ischemia-induced delayed
      neuronal death in the hippocampal CA1 region was observed seven days after
      reperfusion. Pretreatment with glial cell line-derived neurotrophic factor (1.0
      microg), which was directly microinjected into the right hippocampal CA1 region,
      gave significant protection against the delayed hippocampal neuronal death. On
      the contralateral side of the hippocampus, which was not injected with glial cell
      line-derived neurotrophic factor, delayed neuronal death similar to that seen in
      vehicle-treated control animals was observed. Intracerebroventricular glial cell
      line-derived neurotrophic factor (2.5 microg) injection also protected against
      delayed neuronal death. In addition, pretreatment with glial cell line-derived
      neurotrophic factor gave significant protection against apoptotic cell death
      induced by brain ischemia in the hippocampal CA1 region, as determined by in situ
      staining for DNA fragmentation. These findings suggest that glial cell line
      derived neurotrophic factor plays an important role in delayed neuronal death
      induced by brain ischemia.

PMID- 10199602
TI  - The effects of the N-terminal tripeptide of insulin-like growth factor-1, glycine
      proline-glutamate in different regions following hypoxic-ischemic brain injury in
      adult rats.
AB  - Insulin-like growth factor-1 has pleiotropic effects in the central nervous
      system and can act both as a survival and a differentiation factor. Insulin-like
      growth factor-1 can be proteolytically cleaved into des-N-(1-3)-insulin-like
      growth factor-1 and a N-terminal tripeptide fragment, glycine-proline-glutamate.
      Both insulin-like growth factor-1 and des-N-(1-3)-insulin-like growth factor-1
      can improve neuronal survival after hypoxic-ischemic brain injury in vivo. The
      present study investigates the effects of glycine-proline-glutamate on different
      brain regions and neuronal populations after hypoxic-ischemic injury. Unilateral
      hypoxic-ischemic injury was induced in adult rats. Glycine-proline-glutamate (3
      microg) was administered centrally 2 h after the injury and the extent of brain
      damage determined five days later. In a separate trial immunohistochemical
      techniques were used to determine the effects of glycine-proline-glutamate on
      specific populations of neurons in the striatum after the injury. Compared to the
      vehicle treatment, glycine-proline-glutamate (n=19) treatment reduced the extent
      of cortical damage and neuronal loss in the CA1-2 subregions of the hippocampus
      (P<0.05). In the striatum, there was a trend towards a reduction in neuronal loss
      after glycine-proline-glutamate treatment (P=0.053) compared to the vehicle
      (n=21)-treated animals. In a separate study, glycine-proline-glutamate (n=8)
      treatment prevented the loss of choline acetyltransferase (P<0.05), glutamate
      acid decarboxylase (P<0.05) and somatostatin (P<0.05) containing neurons in the
      ipsilateral striatum following hypoxic-ischemic brain injury and also increased
      the numbers of neuronal nitric oxide synthase (P<0.05) containing neurons in the
      contralateral side. These studies suggest that in addition to neuroprotective
      effects, glycine-proline-glutamate can influence neuronal activity after hypoxic
      ischemic injury.

PMID- 10199603
TI  - Neural activity of supplementary and primary motor areas in monkeys and its
      relation to bimanual and unimanual movement sequences.
AB  - A chronic single-unit study of motor cortical activity was undertaken in two
      monkeys trained to perform a bimanually coordinated task. The hypothesis was
      tested that the supplementary motor area plays a specific role in coordinating
      the two hands for common goal-oriented actions. With this objective, a special
      search was made for neurons that might exhibit properties exclusively related to
      bimanual task performance. Monkeys learned to reach for and to pull open a spring
      loaded drawer with one hand, while the other hand reached out to grasp food from
      the drawer recess. The two hands were precisely coordinated for achievement of
      this goal. Monkeys also performed, in separate blocks of trials, only the pulling
      or grasping movements, using the same hands as in the bimanual task. Task-related
      activity of 348 neurons from the supplementary motor area and 341 neurons from
      the primary motor area, each examined in the bimanual and in both unimanual
      tasks, was recorded in the two hemispheres. Most neurons from the supplementary
      motor area were recorded within its caudal microexcitable portion. Contrary to
      expectation, the proportion of neurons with activity patterns related exclusively
      to the bimanual task was small, but somewhat higher in the supplementary motor
      area (5%) than in the primary motor cortex (2%). Another group of neurons that
      were equally modulated during the bimanual as well as to both unimanual task
      components might also contribute in controlling bimanual actions. Such "task
      dependent" rather than "effector-dependent" activity patterns were more common in
      neurons of the supplementary motor area (19%) than of the primary motor cortex
      (5%). Bilateral receptive fields were also more numerous among the supplementary
      motor area neurons. However, a large majority of neurons from primary and
      supplementary motor areas had activity profiles clearly related only to
      contralateral hand movements (65% in the primary motor and 51% in the
      supplementary motor area). A similar group of neurons showed an additional slight
      modulation with ipsilateral movements; they were equally common in the two areas
      (14% and 16%, respectively) and their significance for bimanual coordination is
      questionable. Summed activity profiles of all neurons recorded in the primary and
      supplementary motor areas of the same hemisphere were compared. The modulations
      of the three histograms, corresponding to the two unimanual and the bimanual
      tasks, were similar for the two motor areas, i.e. prominent with bimanual and
      contralateral movements and weak with ipsilateral movements. It is concluded that
      the supplementary motor area is likely to contribute to bimanual coordination,
      perhaps more than the primary motor cortex, but that it is not a defining
      function for the former cortical area. Instead, it is suggested that the
      supplementary motor area is part of a callosally interconnected and distributed
      network of frontal and parietal cortical areas that together orchestrate bimanual
      coordination.

PMID- 10199604
TI  - Nitric oxide synthase neurons in different areas of normal aged and Alzheimer's
      brains.
AB  - This study investigated the distribution of nitric oxide synthase-containing
      neurons in the cerebral cortex of individuals with Alzheimer's disease, and
      compared them with age-matched controls. Paraffin-embedded sections of the
      frontal (area 10), occipital (area 17) and entorhinal cortices (area 28), and
      hippocampal formation obtained from 13 autopsy cases were used in the study.
      Neurons expressing nitric oxide synthase messenger RNA and protein were
      identified, respectively, by in situ hybridization and immunohistochemistry.
      Optical densities of nitric oxide synthase-positive neurons were assessed in 50
      randomly selected fields of each of the above regions of the cortices, in each
      case by microscopic photometry. In the frontal cortex of the Alzheimer group,
      while a decrease in the number of nitric oxide synthase-positive neurons was
      evident, the nitric oxide synthase neurons, on the other hand, showed an
      increased optical density in layers II-IV when compared with those of normal
      ageing. In the occipital cortices, no significant differences in optical density
      were recorded between the normal ageing and Alzheimer specimens. In the
      entorhinal cortex, the optical densities of nitric oxide synthase neurons were
      again similar between the Alzheimer and age-matched control groups. In the
      hippocampar formation itself, there was an increase of nitric oxide synthase
      staining in the Alzheimer patients. These results show that (i) nitric oxide
      synthase neurons are abundant in the human cortex, (ii) the distribution of
      nitric oxide synthase neurons differs between different cortical regions, and
      (iii) there are differences between normal ageing and Alzheimer patients in the
      frontal cortex and the hippocampus.

PMID- 10199605
TI  - The mosaic of brain glial hyperactivity during normal ageing and its attenuation
      by food restriction.
AB  - Food restriction of adult rodents increases lifespan, with commensurate
      attenuation of age-related pathological lesions in many organs, as well as
      attenuation of normal ageing changes that are distinct from gross lesions.
      Previous work showed that chronic food restriction attenuated age-associated
      astrocyte and microglial hyperactivity in the hippocampal hilus, as measured by
      expression of glial fibrillary acidic protein and major histocompatibility
      complex II antigen (OX6). Here, we examined other markers of astrocyte and
      microglial activation in gray and white matter regions of ad libitum-fed (Brown
      Norway x Fischer 344) F1 male rats aged three and 24 months and chronic food
      restricted rats aged 24 months. In situ hybridization and immunohistochemical
      techniques evaluated glial expression of glial fibrillary acidic protein,
      apolipoprotein E, apolipoprotein J (clusterin), heme oxygenase-1, complement 3
      receptor (OX42), OX6 and transforming growth factor-beta1. All markers were
      elevated in the corpus callosum during ageing and were attenuated by food
      restriction, but other regions showed marked dissociation of the extent and
      direction of changes. Astrocytic activation, as measured with glial fibrillary
      acidic protein expression (coding and intron-containing RNA, immunoreactivity),
      increased with age in the corpus callosum, basal ganglia and hippocampus.
      Generally, food restriction attenuated the age-related increase in glial
      fibrillary acidic protein messenger RNA and immunoreactivity. Food restriction
      also reduced the age-related increase in apolipoprotein J and E messenger RNA and
      heme oxygenase-1 immunoreactivity in the basal ganglia and corpus callosum.
      However, astrocytes in the hilus of the hippocampus showed an age-related
      decrease in apolipoprotein J and E messenger RNA, which was further intensified
      by food restriction. The age-associated microglial activation measured by OX6 and
      OX42 immunoreactivity was reduced by food restriction in most subregions. The
      localized subsets of glial age changes and effects of food restriction comprise a
      mosaic of ageing consistent with the regional heterogeneity of ageing changes
      reported by others. In particular, age has a differential effect on astrocytic
      and microglial hyperactivity in gray versus white matter areas. The evident
      mosaic of glial ageing and responses to food restriction suggests that multiple
      mechanisms are at work during ageing.

PMID- 10199606
TI  - Dopamine and serotonin imbalances in the left anterior cingulate and pyriform
      cortices following the repeated intermittent administration of cocaine.
AB  - Studies on the neurobiology of cocaine abuse suggest that cocaine directly
      modifies the activity of dopamine neurons projecting from the dopamine
      synthesizing cells of the ventral tegmental area to the nucleus accumbens. The
      repeated use of cocaine produces persistent adaptations within the
      mesocorticolimbic system and the resulting changes in monoamine neurotransmission
      may lead to behavioral sensitization. The present series of experiments sought to
      determine the effects of the repeated, intermittent challenge that took place two
      days after discontinuation of the pretreatment regimen; (ii) the ex vivo levels
      of biogenic monoamines, choline and acetylcholine in the nucleus accumbens, the
      dorsolateral caudate nucleus, as well as the anterior cingulate, frontal motor,
      frontal somatosensory and pyriform cortices; and (iii) the degree of
      neurochemical relationship between the left and right hemispheres. The repeated
      administration of cocaine produced sensitized behavioral responses to a
      subsequent challenge. Neurochemical correlates of repeated cocaine administration
      were observed at the cortical level and included a significant decrease in
      serotonin levels in the left anterior cingulate and pyriform cortices and an
      increase in dopamine metabolism in the left pyriform cortex. Furthermore, a shift
      in the interhemispheric coupling coefficient matrix for dopamine
      neurotransmission was observed in both the pyriform cortex and nucleus accumbens
      of cocaine-sensitized animals suggesting that, in these structures, the two
      hemispheres are operating independently. These results demonstrate that cocaine
      produces alterations in specific dopaminergic and serotonergic pathways that
      arise from the mesencephalon and project towards both the anterior cingulate and
      pyriform cortices.

PMID- 10199607
TI  - Recurrent seizures and hippocampal sclerosis following intrahippocampal kainate
      injection in adult mice: electroencephalography, histopathology and synaptic
      reorganization similar to mesial temporal lobe epilepsy.
AB  - Human mesial temporal lobe epilepsy is characterized by hippocampal seizures
      associated with pyramidal cell loss in the hippocampus and dispersion of dentate
      gyrus granule cells. A similar histological pattern was recently described in a
      model of extensive neuroplasticity in adult mice after injection of kainate into
      the dorsal hippocampus [Suzuki et al. (1995) Neuroscience 64, 665-674]. The aim
      of the present study was to determine whether (i) recurrent seizures develop in
      mice after intrahippocampal injection of kainate, and (ii) the
      electroencephalographic, histopathological and behavioural changes in such mice
      are similar to those in human mesial temporal lobe epilepsy. Adult mice receiving
      a unilateral injection of kainate (0.2 microg; 50 nl) or saline into the dorsal
      hippocampus displayed recurrent paroxysmal discharges on the
      electroencephalographic recordings associated with immobility, staring and,
      occasionally, clonic components. These seizures started immediately after kainate
      injection and recurrid for up to eight months. Epileptiform activities occurred
      most often during sleep but occasionally while awake. The pattern of seizures did
      not change over time nor did they secondarily generalize. Glucose metabolic
      changes assessed by [14C]2-deoxyglucose autoradiography were restricted to the
      ipsilateral hippocampus for 30 days, but had spread to the thalamus by 120 days
      after kainate. Ipsilateral cell loss was prominent in hippocampal pyramidal cells
      and hilar neurons. An unusual pattern of progressive enlargement of the dentate
      gyrus was observed with a marked radial dispersion of the granule cells
      associated with reactive astrocytes. Mossy fibre sprouting occurred both in the
      supragranular molecular layer and infrapyramidal stratum oriens layer of CA3. The
      expression of the embryonic form of the neural cell adhesion molecule coincided
      over time with granule cell dispersion. Our data describe the first histological,
      electrophysiological and behavioural evidence suggesting that discrete
      excitotoxic lesions of the hippocampus in mice can be used as an isomorphic model
      of mesial temporal lobe epilepsy.

PMID- 10199608
TI  - Effects of pH changes on calcium-mediated potentials in rat hippocampal neurons
      in vitro.
AB  - The effects of changes in extra- and intracellular pH (pHo and pHi, respectively)
      on potentials mediated by the influx of Ca2+ ions were investigated in
      intracellular "current-clamp" recordings from CA1 pyramidal neurons in rat
      hippocampal slices. In neurons which exhibited a "regular-spiking" discharge in
      response to depolarizing current injection at pH 7.3, perfusion with pH 7.7
      medium led to the development of burst firing. Conversely, neurons which were
      "burst-firing" at pH 7.3 became regular spiking upon exposure to pH 6.9 medium.
      In addition, the rebound depolarization following a current-evoked
      hyperpolarization to >- 60 mV, which in part reflects activation of a low-voltage
      activated Ca2+ conductance, was reduced at pHo 6.9 and enhanced at pHo 7.7.
      Neither the burst firing pattern of discharge nor the augmented rebound
      depolarization observed during perfusion with pH 7.7 medium was due to the
      reduction in [Cl-]o consequent upon the increase in [HCO3-]o at a constant PCO2.
      The magnitudes of the fast afterhyperpolarization which follows a single
      depolarizing current-evoked action potential and the slow afterhyperpolarization
      which follows a train of action potentials were attenuated and enhanced,
      respectively, during perfusion with pH 6.9 and pH 7.7 media, compared to
      responses obtained at pH 7.3. Reducing pHi at a constant pHo (by exposure to pH
      7.3 HCO3-/CO2-free medium buffered with 30 mM HEPES) also attenuated fast and
      slow afterhyperpolarizations. In tetrodotoxin- and tetraethylammonium-poisoned
      slices, perfusion with pH 6.9 and pH 7.7 media reduced and increased,
      respectively, the magnitude of current-evoked Ca2+-dependent depolarizing
      potentials and their associated slow afterhyperpolarizations, compared with
      responses obtained at pH 7.3. In contrast, reducing pHi at a constant pHo
      elicited only a small reduction in the magnitude of Ca2+ spikes but markedly
      attenuated the subsequent slow afterhyperpolarization. The results suggest that,
      in rat CA1 hippocampal pyramidal neurons, Ca2+-dependent depolarizing potentials
      mediated by the influx of Ca2+ ions through voltage-activated Ca2+ channels are
      sensitive to changes in pHo. These effects of changes in pHo are not dependent
      upon changes in pHi consequent upon the changes in pHo. Changes in pHo also
      affect the magnitudes of fast and slow afterhyperpolarizations mediated by Ca2+
      dependent K+ conductances. In these cases, however, the effects of changes in pHo
      are mimicked by changes in pHi at a constant pHo, suggesting in turn that the
      effects of changes in pHo on fast and slow afterhyperpolarizations may be
      mediated both by changes in Ca2+ influx (reflecting mainly changes in pHo) and by
      direct effects of changes in pHi (consequent upon changes in pHo) on Ca2+
      dependent K+ conductances.

PMID- 10199609
TI  - Ventral hippocampal dopamine D1 and D2 systems and spatial working memory in
      rats.
AB  - The hippocampus has long been known to be important for memory function. However,
      the involvement of hippocampal dopamine systems with memory has received little
      attention. In the current study, dopamine D1 and D2 hippocampal receptor system
      involvement with memory was assessed in female Sprague-Dawley rats by local
      infusion of D1 and D2 agonists and antagonists into the ventral hippocampus.
      Working memory performance was assessed on the radial-arm maze. Neither the D1
      agonist dihydrexidine (1.1-10 microg/side) nor the D1 antagonist SCH 23390 (0.19
      1.67 microg/side) was effective in significantly altering radial-arm maze choice
      accuracy. In contrast, there were significant and opposite effects of D2 agonist
      and antagonist treatments. The D2 agonist quinpirole caused a significant
      (P<0.05) dose-related improvement in choice accuracy over a dose range of 1.1-10
      microg/side. In a complementary fashion, the D2 antagonist raclopride caused a
      significant (P<0.05) dose-related choice accuracy deficit over a range of 0.19
      1.67 microg/side. This study provides clear evidence that hippocampal D2 activity
      is positively related to working memory performance, while evidence for D1
      systems is less compelling. Dopamine D2 receptors in the ventral hippocampus were
      shown to have important influences on spatial working memory. In a consistent
      pattern of effects ventral hippocampal infusion of the D2 agonist quinpirole
      improved working memory performance in the radial-arm maze, while ventral
      hippocampal infusion of the D2 antagonist raclopride impaired performance.

PMID- 10199610
TI  - Blockade of N-methyl-D-aspartate receptors in the insular cortex disrupts taste
      aversion and spatial memory formation.
AB  - The present experiments examined the effects of direct intracortical
      microinjections of the N-methyl-D-aspartate receptor antagonist 2-amino-5
      phosphonovaleric acid directly into the insular cortex of rats, before or
      immediately after training of conditioned taste aversion and the water maze
      spatial learning task. In the first series of experiments animals received
      bilateral injections of 2-amino-5-phosphonovaleric acid prior to taste aversion
      conditioning or spatial training. A strong disruptive effect was found in the
      acquisition of training tasks. To determine the possible involvement of N-methyl
      D-aspartate receptors in the early post-training processes taking place in the
      cortex during both learning paradigms, in a second series of experiments, animals
      received bilateral 2-amino-5-phosphonovaleric acid microinjections 30, 60 or 120
      min after the acquisition trial, and 15 min before the retention test. For
      spatial learning successive treatments were independently done either starting at
      the onset of the asymptotic phase of the learning curve, 0, 30 or 120 min after
      finishing the training session, as well as 15 min before the retention test
      trial. The conditioned taste aversion task remained sensitive to N-methyl-D
      aspartate blockade during a period of at least 2 h after the first presentation
      of the gustatory stimulus, while in the case of the spatial learning task, a
      gradually decreasing effect was observed from the onset of the asymptotic phase
      onwards. Taken together, these results provide direct evidence for N-methyl-D
      aspartate receptor involvement in cortical regulation of memory formation.
      Furthermore, our results suggest that in the same cortical region, a different
      time-course for the activation of N-methyl-D-aspartate-dependent mechanisms
      occurs during the early formation of cortically mediated memories, depending on
      the particular behavioural task.

PMID- 10199611
TI  - Quantification of cholinergic and select non-cholinergic mesopontine neuronal
      populations in the human brain.
AB  - The pars compacta and pars dissipata of the pedunculopontine nucleus contain
      cholinergic cell group Ch5, and the laterodorsal tegmental nucleus contains
      cholinergic cell group Ch6. The pedunculopontine nucleus has been implicated in a
      variety of functions, including mediation of rapid eye movement sleep and in
      extrapyramidal motor function, although the role of cholinergic and non
      cholinergic neurons is unclear. Quantitative neuroanatomical techniques were used
      to map the distribution of cholinergic neurons in the mesopontine nuclei of the
      adult human brain. In addition, the number and distribution of comparably sized
      non-cholinergic neurons at selected anatomical levels were compared. An antibody
      raised against human choline acetyltransferase was used to stain
      immunohistochemically the mesopontine neurons in six brains, ranging in age from
      28 to 60 years. The rostrocaudal length of the Cb5/Ch6 cell complex was
      approximately 10 mm. The estimated total number of cells was similar for all
      brains, and varied by less than 7%. The estimated average number of cholinergic
      cells in the combined pedunculopontine and laterodorsal tegmental nuclei was
      approximately 20,000, with 30% of the cells in the pedunculopontine nucleus pars
      compacta, 57% in the pedunculopontine nucleus pars dissipata and 13% in the
      laterodorsal tegmental nucleus. There was no correlation between cell number and
      age. Within areas of mesopontine tegmentum occupied by the Ch5 cholinergic
      neurons, there were often more noncholinergic neurons than comparably sized
      cholinergic neurons. The present study provides detailed maps of the distribution
      and number of mesopontine cholinergic neurons in the normal human brain. Many non
      cholinergic neurons are intermixed with the cholinergic pedunculopontine neurons.
      One region of the pedunculopontine nucleus pars dissipata containing few
      cholinergic neurons, located adjacent to the ventral border of the
      pedunculopontine nucleus pars compacta, may correspond to the midbrain
      extrapyramidal area as defined previously in rodent and in non-human primate.
      These data will be useful for quantitative neuropathological studies concerning
      the role of both cholinergic and non-cholinergic mesopontine neurons in diseases
      proposed to affect these neurons, including Parkinson's disease, schizophrenia
      and progressive supranuclear palsy.

PMID- 10199612
TI  - Presynaptic markers of cholinergic function in the rat brain: relationship with
      age and cognitive status.
AB  - The nature of age-related changes in cholinergic function and their relationship
      to age-related behavioral decline were examined in the present study. Male
      Fischer-344 rats of four ages (four, 11, 17 and 23 months) were tested in a
      battery of cognitive tasks. Discrete microdissections of brain areas involved in
      cognitive function were performed, and activity of choline acetyltransferase and
      levels of hemicholinium-3 binding were determined to assess the integrity of
      cholinergic innervation. Age-related changes in cholinergic markers occurred
      predominantly in the medial septal area and its target areas (hippocampus and
      cingulate cortex), and were also present in the posterior caudate. However, most
      of the age-related changes in cholinergic markers were already present at ages at
      which behavioral impairment was not yet maximal. There were some consistent
      correlations between behavioral and neurochemical measures, independent of age,
      but these accounted for relatively small proportions of variance in behavioral
      performance. For most of these correlations, lower levels of presynaptic
      cholinergic markers were related to better behavioral performance. In brain areas
      in which correlations changed with age, lower levels of presynaptic cholinergic
      markers were associated with better performance in young rats, whereas higher
      levels were associated with better performance in aged rats. Recent lesion
      studies using a toxin selective for basal forebrain cholinergic neurons have
      suggested that these neurons do not play as central a role in learning and memory
      in young and aged animals as was previously thought. When considered in this
      context, the present results suggest that preserved cholinergic function in old
      age might act indirectly to sustain cognitive ability. Changes in cholinergic
      function may represent one of a number of age-related neurobiological events that
      underlie behavioral impairments, or may be a permissive factor for other age
      related processes that are more directly responsible for cognitive impairments.

PMID- 10199613
TI  - Dopamine D1 receptor modulation of glutamate receptor messenger RNA levels in the
      neocortex and neostriatum of unilaterally 6-hydroxydopamine-lesioned rats.
AB  - The effect of treatment with the D1 dopamine receptor agonist SKF 38393 on the
      expression of metabotropic glutamate receptor 1, 3, 4 and 5 receptor subtypes and
      of the glutamate N-methyl-D-aspartate ionotropic receptor subunits NRI, NR2A and
      NR2B was analysed using in situ hybridization. We studied the neocortex and
      neostriatum of normal rats and of rats unilaterally treated with 6
      hydroxydopamine, a neurotoxin that, after intracerebral injection into the
      ventral tegmental area, causes selective degeneration of the ascending dopamine
      pathway. In the 6-hydroxydopamine-lesioned rats, metabotropic glutamate receptor
      subtype 3 messenger RNA levels were ipsilaterally increased in the neocortex and
      neostriatum, while the levels of metabotropic glutamate receptor subtype 4
      messenger RNA were bilaterally increased in both regions. When administered to
      the 6-hydroxydopamine-lesioned rats, the D1 receptor agonist SKF 38393 (3 x 20
      mg/kg, s.c.) produced a bilateral decrease in the expression of the metabotropic
      glutamate receptor subtype 1 and 5 receptor messenger RNA levels in the neocortex
      and neostriatum. In the neostriatum, SKF 38393 attenuated the ipsilateral
      increase in the expression of striatal metabotropic glutamate receptor subtype 3
      messenger RNA produced by the 6-hydroxydopamine lesion. Furthermore, SKF 38393
      produced a bilateral decrease in the levels of NRI receptor subunit messenger RNA
      and, in contrast, an increase in the striatal NR2B messenger RNA levels. All of
      these effects were abolished by the D1 receptor antagonist SCH 23360. These
      results indicate a differential D1 receptor-mediated modulation of the expression
      of some glutamate receptor subtypes in the neostriatum and neocortex, in
      agreement with the idea of a functional coupling between dopamine and excitatory
      amino acid systems in both regions. Thus, pharmacological targeting of excitatory
      amino acid systems could provide alternative or complementary treatment
      strategies for diseases involving dopaminergic systems in the striatum (e.g.,
      Parkinson's disease) and cortex (e.g., schizophrenia).

PMID- 10199614
TI  - Striatal, pallidal, and pars reticulata evoked inhibition of nigrostriatal
      dopaminergic neurons is mediated by GABA(A) receptors in vivo.
AB  - Dopaminergic neurons express both GABA(A) and GABA(B) receptors and GABAergic
      inputs play a significant role in the afferent modulation of these neurons.
      Electrical stimulation of GABAergic pathways originating in neostriatum, globus
      pallidus or substantia nigra pars reticulata produces inhibition of dopaminergic
      neurons in vivo. Despite a number of prior studies, the identity of the GABAergic
      receptor subtype(s) mediating the inhibition evoked by electrical stimulation of
      neostriatum, globus pallidus, or the axon collaterals of the projection neurons
      from substantia nigra pars reticulata in vivo remain uncertain. Single-unit
      extracellular recordings were obtained from substantia nigra dopaminergic neurons
      in urethane anesthetized rats. The effects of local pressure application of the
      selective GABA(A) antagonists, bicuculline and picrotoxin, and the GABA(B)
      antagonists, saclofen and CGP-55845A, on the inhibition of dopaminergic neurons
      elicited by single-pulse electrical stimulation of striatum, globus pallidus, and
      the thalamic axon terminals of the substantia nigra pars reticulata projection
      neurons were recorded in vivo. Striatal, pallidal, and thalamic induced
      inhibition of dopaminergic neurons was always attenuated or completely abolished
      by local application of the GABA(A) antagonists. In contrast, the GABA(B)
      antagonists, saclofen or CGP-55845A, did not block or attenuate the stimulus
      induced inhibition and at times even increased the magnitude and/or duration of
      the evoked inhibition. Train stimulation of globus pallidus and striatum also
      produced an inhibition of firing in dopaminergic neurons of longer duration.
      However this inhibition was largely insensitive to either GABA(A) or GABA(B)
      antagonists although the GABA(A) antagonists consistently blocked the early
      portion of the inhibitory period indicating the presence of a GABA(A) component.
      These data demonstrate that dopaminergic neurons of the substantia nigra pars
      compacta are inhibited by electrical stimulation of striatum, globus pallidus,
      and the projection neurons of substantia nigra pars reticulata in vivo. This
      inhibition appears to be mediated via the GABA(A) receptor subtype, and all three
      GABAergic afferents studied appear to possess inhibitory presynaptic GABA(B)
      autoreceptors that are active under physiological conditions in vivo.

PMID- 10199615
TI  - GABAergic control of rat substantia nigra dopaminergic neurons: role of globus
      pallidus and substantia nigra pars reticulata.
AB  - Dopaminergic neurons in vivo fire spontaneously in three distinct patterns or
      modes. It has previously been shown that the firing pattern of substantia nigra
      dopaminergic neurons can be differentially modulated by local application of
      GABA(A) and GABA(B) receptor antagonists. The GABA(A) antagonists, bicuculline or
      picrotoxin, greatly increase burst firing in dopaminergic neurons whereas GABA(B)
      antagonists cause a modest shift away from burst firing towards pacemaker-like
      firing. The three principal GABAergic inputs to nigral dopaminergic neurons arise
      from striatum, globus pallidus and from the axon collaterals of nigral pars
      reticulata projection neurons, each of which appear to act in vivo primarily on
      GABA(A) receptors (see preceding paper). In this study we attempted to determine
      on which afferent pathway(s) GABA(A) antagonists were acting to cause burst
      firing. Substantia nigra dopaminergic neurons were studied by single unit
      extracellular recordings in urethane anesthetized rats during pharmacologically
      induced inhibition and excitation of globus pallidus. Muscimol-induced inhibition
      of pallidal neurons produced an increase in the regularity of firing of nigral
      dopaminergic neurons together with a slight decrease in firing rate. Bicuculline
      induced excitation of globus pallidus neurons produced a marked increase in burst
      firing together with a modest increase in firing rate. These changes in firing
      rate were in the opposite direction to what would be expected for a monosynaptic
      GABAergic pallidonigral input. Examination of the response of pars reticulata
      GABAergic neurons to similar manipulations of globus pallidus revealed that the
      firing rates of these neurons were much more sensitive to changes in globus
      pallidus neuron firing rate than dopaminergic neurons and that they responded in
      the opposite direction. Pallidal inhibition produced a dramatic increase in the
      firing rate of pars reticulata GABAergic neurons while pallidal excitation
      suppressed the spontaneous activity of pars reticulata GABAergic neurons. These
      data suggest that globus pallidus exerts significant control over the firing rate
      and pattern of substantia nigra dopaminergic neurons through a disynaptic pathway
      involving nigral pars reticulata GABAergic neurons and that at least one
      important way in which local application of bicuculline induces burst firing of
      dopaminergic neurons is by disinhibition of this tonic inhibitory input.

PMID- 10199616
TI  - Opposite tonic modulation of dopamine and adenosine on c-fos gene expression in
      striatopallidal neurons.
AB  - The impulse flow-dependent dopamine release in the striatum was acutely blocked
      by unilateral lesion of the medial forebrain bundle with 6-hydroxydopamine.
      Within 45 min this disruption reduced the striatal extracellular dopamine levels
      by 80% as determined by in vivo voltammetry. A strong induction of c-fos
      messenger RNA was detected in the ipsilateral dorsolateral striatum 75 min after
      6-hydroxydopamine injection by in situ hybridization. Double labelling
      demonstrates that this induction was confined to neurons expressing the dopamine
      D2 receptor messenger RNA. At this time-point, there were no changes in the
      striatal levels of either tyrosine hydroxylase immunoreactivity or dopamine D2
      receptor messenger RNA. The c-fos messenger RNA expression induced by acute 6
      hydroxydopamine injection was abolished by intraperitoneal pretreatment with the
      dopamine D2 receptor agonist, quinelorane (2 mg/kg) and strongly reduced by
      administration of the selective adenosine A2A receptor antagonist SCH-58261 (5
      mg/kg). The results reported here show, by using a novel methodological approach,
      that an acute decrease of dopamine release causes an induction of c-fos messenger
      RNA in dopamine D2 receptor-containing striatopallidal neurons. This, together
      with previous findings, demonstrates that the c-fos gene expression is tonically
      inhibited by the impulse flow-dependent dopamine release via D2 receptors. In
      addition, this study provides evidence that endogenous adenosine, acting via
      adenosine A2A receptors, induces striatal c-fos messenger RNA when extracellular
      dopamine levels are strongly reduced. Thus endogenous dopamine and adenosine
      exert opposite effects on the activity of the D2-containing striatopallidal
      neurons.

PMID- 10199617
TI  - Differential distribution of N-methyl-D-aspartate receptor-2 subunit messenger
      RNA in the rat superior olivary complex.
AB  - The distribution of N-methyl-D-aspartate receptor subunit messenger RNA was
      examined in the superior olivary complex of the rat using in situ hybridization
      methods. Non-radioactive methods showed N-methyl-D-aspartate receptor-1 and N
      methyl-D-aspartate receptor-2A, -2B and -2C subunit expression to be abundant in
      principal cells of all major superior olivary complex regions, with N-methyl-D
      aspartate receptor-1 expression higher than N-methyl-D-aspartate receptor-2.
      After auto-radiographic in situ hybridization, counting silver grains over cells
      was used to quantitate and compare levels of expression of the N-methyl-D
      aspartate receptor-2 subunits. N-Methyl-D-aspartate receptor-2A, -2B and -2C
      expression was detected over cells in the lateral and medial superior olive, the
      medial, lateral and ventral nucleus of the trapezoid body, and the superior
      paraolivary nucleus. N-Methyl-D-aspartate receptor-2D expression was only
      observed in the lateral superior olive, lateral nucleus of the trapezoid body and
      ventral nucleus of the trapezoid body. Three distinct patterns of labeling were
      observed. The lateral superior olive and ventral nucleus of the trapezoid body
      showed higher expression of N-methyl-D-aspartate receptor-2A and -2C than other
      subunits; the medial nucleus of the trapezoid body showed higher N-methyl-D
      aspartate receptor-2B expression than other subunits; and the medial superior
      olive, superior paraolivary nucleus and ventral nucleus of the trapezoid body
      showed relatively equivalent expression of N-methyl-D-aspartate receptor-2A, -2B
      and -2C subunits. N-Methyl-D-aspartate receptor-2D had the lowest expression,
      with levels greater than background in only the lateral superior olive, ventral
      nucleus of the trapezoid body and lateral nucleus of the trapezoid body.
      Immunocytochemistry using antibodies to N-methyl-D-aspartate receptor-2A, -2B and
      -2C showed immunolabeling consistent with in situ hybridization results. These
      results show diversity in expression of N-methyl-D-aspartate receptor-2 subunits
      in different superior olivary complex regions and would predict pharmacological
      differences.

PMID- 10199618
TI  - Effect of iron and lipid peroxidation on development of cerebellar granule cells
      in vitro.
AB  - The aim of this study was to investigate the effect of chelated ferric ion on
      neuronal development in vitro using cultured cerebellar granule cells of the rat.
      The cells were exposed to ferric nitrilotriacetate at varying concentrations for
      seven or 14 days. In addition to morphological studies, protein content
      determination and malondialdehyde measurement were performed. The study showed
      that cell development, with the addition of a lower concentration of chelated
      ferric ion (5 microM), could be kept in a normal condition, no significant
      changes in protein content and malondialdehyde production being found as compared
      with those of the controls, while the addition of higher concentrations of
      chelated ferric ion (> or = 10 microM) to the cultures demonstrated an adverse
      effect on development of cerebellar granule cell in vitro. Determination of
      protein content showed that the neuronal population decreased significantly, and
      the neuronal loss was inversely proportional to the iron concentrations added.
      Malondialdehyde measurement demonstrated that the extent of lipid peroxidation
      reaction increased remarkably with increasing iron concentration. A very close
      and highly significant correlation (gamma=0.985) between changes of
      malondialdehyde production and protein content was observed. These results
      suggest that the neuronal loss in the cultures with higher concentrations of iron
      was due to lipid peroxidation reaction induced by the addition of iron, and that
      iron overload might accelerate the process of ageing and death of cerebellar
      granule cells in vitro.

PMID- 10199619
TI  - Characterization of a hyperpolarizing-activated current in rat lateral
      parabrachial neurons.
AB  - The present study examined the electrophysiological and kinetic properties of a
      hyperpolarizing-activated current in neurons located in the lateral parabrachial
      nucleus. We investigated whether differences observed in the shape of action
      potential afterhyperpolarizations in lateral parabrachial nucleus neurons, and
      the ability of these neurons to accommodate, correlated with the presence of this
      current. A voltage-activated inwardly rectifying current that increased in
      amplitude with hyperpolarization was observed in 83% of the neurons examined.
      Under voltage-clamp recording conditions, this current activated at about -70 mV,
      was half-activated at -96.5 mV and was blocked by bath application of 2 mM
      cesium, but not by 100 microM barium. In the current-clamp mode, activation of
      this current resulted in a transient increase in neuronal excitability at the
      termination of the more negative current injections. The presence of this current
      did not correlate with specific action potential characteristics or the ability
      of lateral parabrachial nucleus neurons to accommodate, as the kinetics and
      voltage-dependent characteristics are such that this hyperpolarizing-activated
      current does not affect neuronal excitability at or near the resting membrane
      potential. However, it may act as an important depolarizing mechanism that
      prevents neurons from becoming unresponsive when they are excessively
      hyperpolarized, These results provide evidence that the majority of neurons
      located in the lateral parabrachial nucleus exhibit a mixed cationic current,
      which is consistent with the H-current or Q-current. This current may function as
      a negative feedback mechanism that is activated under conditions of intense
      hyperpolarization so as to ensure that lateral parabrachial nucleus neurons are
      in a more suitable state of readiness to respond appropriately to afferent input.

PMID- 10199620
TI  - Distribution of metabotropic glutamate receptors in the parabrachial and Kolliker
      Fuse nuclei of the rat.
AB  - In the present study, we analysed the distribution and cellular localization of
      metabotropic glutamate receptors (1alpha, 2/3, 5) in parabrachial and Kolliker
      Fuse nuclei using subtype-specific antisera. Immunolabelling revealed that
      different nuclei express different sets of metabotropic glutamate receptors.
      Metabotropic glutamate receptor la immunoreactivity was found in the Kolliker
      Fuse nucleus and in several parabrachial nuclei, including the waist area,
      lateral crescent, medial, external medial and ventral lateral nuclei. The
      external lateral and internal lateral parabrachial nuclei were devoid of
      metabotropic glutamate receptor 1alpha immunoreactivity. Metabotropic glutamate
      receptor 5 immunoreactivity was observed in the Kolliker-Fuse and in the medial
      parabrachial nuclei, while in the remaining nuclei the staining was very weak.
      Again, the external lateral nucleus was devoid of metabotropic glutamate receptor
      5 immunoreactivity. The metabotropic glutamate receptor 2/3 antisera stained all
      lateral parabrachial nuclei as well as the Kolliker-Fuse nucleus, while staining
      in the medial parabrachial nucleus was weak. Metabotropic glutamate receptor
      1alpha immunoreactivity was observed on presumed dendritic profiles, while
      metabotropic glutamate receptor 5 immunoreactivity was found predominantly on
      neuronal cell bodies. Metabotropic glutamate receptor 2/3 immunoreactivity was
      present as a fine, punctate immunostaining in the neuropil. Our data suggest that
      glutamate release in the parabrachial and Kolliker-Fuse nuclei might induce a
      variety of second messenger cascades, as indicated by the presence or absence of
      certain types of metabotropic glutamate receptors.

PMID- 10199621
TI  - Enhancement of GABA-activated current by muscarine in rat dorsal root ganglion
      neurons.
AB  - The modulation of GABA-gated ion channel responses to GABA, pentobarbital and
      diazepam by muscarine was studied in freshly isolated rat dorsal root ganglion
      neurons using a whole-cell patch-clamp technique. Muscarine enhanced current
      activated by 5 microM GABA dose-dependently with an EC50 of 40 +/- 2 microM. This
      potentiation was not blocked by pirenzepine, gallamine and atropine, the specific
      and non-specific muscarinic receptor antagonists. Muscarine shifted the GABA dose
      response curve to the left, with the GABA EC50 decreased from 45 +/- 2 to 13 +/-
      2 microM. The maximal response to GABA was suppressed to 89.3 +/- 4.6% as
      compared with the control (100%) by 80 microM muscarine. Muscarine potentiated
      GABA (1-100 microM)-activated current in a voltage-independent manner. Muscarine
      shifted the dose-response curve for pentobarbital enhancement of GABA-activated
      current to the left, and the enhancement of GABA-activated current by muscarine
      was additive to that of pentobarbital over all pentobarbital concentrations.
      Muscarine shifted the dose-response curve for diazepam (1-100 nM) enhancement of
      GABA-activated current to the left. However, muscarine attenuated the
      facilitatory effect of saturating concentrations of diazepam (> 100 nM). The
      potentiating effect of muscarine was blocked by 1 nM ethyl-beta-carboline-3
      carboxylate, the inverse agonist of benzodiazepine receptors. These results
      suggest that GABA-gated ion channel responses to GABA and pentobarbital were
      potentiated by muscarine and the binding site(s) for muscarine might be related
      to those for diazepam.

PMID- 10199622
TI  - Transgenic mice over-expressing substance P exhibit allodynia and hyperalgesia
      which are reversed by substance P and N-methyl-D-aspartate receptor antagonists.
AB  - A transgenic mouse has been developed which, during development, over-expresses
      nerve growth factor under the control of a myelin basic protein promoter. These
      animals display an ectopic network of substance P-containing sensory fibers in
      the white matter of the spinal cord. To study the functional significance of this
      model to nociception, these mice were studied in a test measuring the latency to
      tail withdrawal from a noxious radiant heat stimulus. Baseline reaction times
      were significantly less in transgenic mice, suggesting thermal allodynia. A
      mechanical stimulus was then applied to the tip of the tail at either 450 g or
      1400 g for 2 s and tail withdrawal readings were taken for another 10 min. In
      control mice, the 450 g stimulus was without effect, suggesting that it is
      normally innocuous. In transgenic mice, this stimulus induced a transient
      decrease in withdrawal latency at 1 min. Thus, transgenic mice exhibited
      mechanical allodynia. The 1400 g stimulus decreased withdrawal latency in both
      transgenic and control mice. However, the response was greater in transgenic
      mice, indicating that they exhibited mechanical hyperalgesia. The neurokinin-1
      receptor antagonist CP-96,345, but not the inactive stereoisomer CP-96,344,
      administered subcutaneously 30 min before the 450 g stimulus, blocked the
      stimulation-induced allodynia in transgenic mice, and revealed a transient
      antinociception in transgenic and control mice. Ketamine, an N-methyl-D-aspartate
      receptor antagonist, given intraperitoneally 10 min before 450 g stimulation,
      blocked the allodynia in transgenic mice. These results indicate that these
      transgenic mice display hyperalgesia and allodynia, and that these nociceptive
      responses are reversed by substance P and N-methyl-D-aspartate receptor
      antagonists.

PMID- 10199623
TI  - Release of substance P, calcitonin gene-related peptide and prostaglandin E2 from
      rat dura mater encephali following electrical and chemical stimulation in vitro.
AB  - Neurogenic inflammation of the dura, expressed in plasma extravasation and
      vasodilatation, putatively contributes to different types of headache. A novel in
      vitro preparation of the fluid-filled skull cavities was developed to measure
      mediator release from dura mater encephali upon antidromic electrical stimulation
      of the trigeminal ganglion and after application of a mixture of inflammatory
      mediators (serotonin, histamine and bradykinin, 10(-5) M each, pH 6.1) to the
      arachnoid side of rat dura. The release of calcitonin gene-related peptide,
      substance P and prostaglandin E2 from dura mater was measured in 5-min samples of
      superfusates using enzyme immunoassays. Orthodromic chemical and antidromic
      electrical stimulation of dural afferents caused significant release of
      calcitonin gene-related peptide (2.8- and 4.5-fold of baseline). The neuropeptide
      was found to be increased during the 5-min stimulation period and returned to
      baseline (20.9 +/- 12 pg/ml) in the sampling period after stimulation. In
      contrast, release of substance P remained at baseline levels (19.3 +/- 11 pg/ml)
      throughout the experiment. Prostaglandin E2 release was elevated during chemical
      and significantly also after antidromic electrical stimulation (6- and 4.2-fold
      of baseline, which was 305 +/- 250 pg/ml). Prostaglandin E2 release outlasted the
      stimulation period for at least another 5 min. The data support the hypothesis of
      neurogenic inflammation being involved in headaches and provide new evidence for
      prostaglandin E2 possibly facilitating meningeal nociceptor excitation and,
      hence, pain.

PMID- 10199624
TI  - Selective targeting of somatostatin receptor 3 to neuronal cilia.
AB  - Recently, five members of the somatostatin receptor family have been cloned.
      However, little is known about their cellular and subcellular localization in the
      central nervous system. Using specific anti-peptide antisera, we observed
      somatostatin receptor 3-like immunoreactivity in many brain regions, including
      the cerebral cortex, hippocampus, hypothalamus, amygdala and cerebellum. In all
      of these regions (except for the cerebellar cortex), somatostatin receptor 3-like
      immunoreactivity was selectively targeted to 4-8-microm-long rod-shaped profiles
      which did not co-localize with axonal or dendritic markers. One immunoreactive
      profile was always associated with one neuronal cell body. This staining pattern
      was resistant to colchicine treatment and showed a closely overlapping
      distribution with somatostatin receptor 3 messenger RNA, suggesting that the
      receptor protein is not transported over long distances. Electron microscopic
      analysis revealed that somatostatin receptor 3-like immunoreactivity is localized
      to the plasma membrane of neuronal cilia which extended into an intercellular
      pocket and showed a 9+0 filament pattern in their basal body and proximal
      segments. Thus, somatostatin receptor 3 demonstrates a unique example of a G
      protein-coupled receptor not localized to "classical" pre- or postsynaptic sites,
      but selectively targeted to neuronal cilia. The presence of the somatostatin
      receptor 3 receptor on neuronal cilia suggests that these presumably non-motile
      cilia may not merely represent developmental remnants, but rather function as
      chemical sensors of the immediate milieu.

PMID- 10199625
TI  - Molecular and behavioral effects mediated by Gs-coupled adenosine A2a, but not
      serotonin 5-Ht4 or 5-Ht6 receptors following antipsychotic administration.
AB  - Typical antipsychotic agents are potent antagonists of Gi-coupled dopamine D2
      receptors, but their mechanisms of action following this initial blockade remain
      poorly understood. We hypothesized that in striatal neurons, interruption of this
      inhibitory dopamine D2 input would unmask endogenous striatal Gs-coupled
      receptors. An increase in cAMP levels generated by these unopposed receptors
      would then lead to the well-described behavioral and molecular effects of
      antipsychotic administration such as catalepsy and striatal c-fos and neurotensin
      gene transcription. We examined three striatal Gs-coupled receptor systems
      (serotonin 5-HT4, serotonin 5-HT6 and adenosine A2a) to assess their potential
      involvement in the mechanism of action of the typical antipsychotic haloperidol.
      Antagonists of each of these three receptor systems together with a 1 mg/kg dose
      of haloperidol were co-administered to Sprague-Dawley rats, and both the degree
      of catalepsy produced in the animals and the induction of striatal c-fos and
      neurotensin messenger RNAs were measured. Both the specific adenosine A2a
      antagonist 8-(3-chlorostyryl)-caffeine and the general adenosine antagonist
      theophylline reduced haloperidol-dependent induction of striatal neurotensin and
      c-fos messenger RNA. Administration of these agents also greatly reduced the
      degree of catalepsy induced by haloperidol. Antagonists of the 5-HT6 receptor
      failed to block the induction of striatal messenger RNAs, but the 5-HT6
      antagonist clozapine (an important atypical antipsychotic agent in its own right)
      was a potent inhibitor of catalepsy. 5-HT4 agents were unable to alter
      haloperidol's effects on striatal messenger RNA levels or catalepsy. We conclude
      that the striatal Gs-coupled adenosine A2a receptor is an important mediator of
      the molecular and behavioral sequelae following haloperidol administration.

PMID- 10199626
TI  - Gonadectomy in adult life increases tyrosine hydroxylase immunoreactivity in the
      prefrontal cortex and decreases open field activity in male rats.
AB  - The prefrontal cortices in rats participate in a range of cognitive, emotional,
      and locomotor functions that are dependent on its rich catecholamine innervation.
      Sex differences identified in many of these functions suggest that the prefrontal
      cortex is also influenced by gonadal hormones. Previous studies have shown that
      prefrontal catecholamines can be modified by changes in the hormone environment
      in developing animals. The present analyses, carried out in male rats
      gonadectomized as adults, with and without supplementation with testosterone
      proprionate, and examined at intervals from two days to 10 weeks after surgery,
      revealed that both the anatomical organization of prefrontal catecholamine
      afferents, and a behavioral measure sensitive to their selective lesioning remain
      highly responsive to changes in testicular hormones in adulthood. Thus,
      gonadectomy in adult male rats rapidly led to a large but transient decrease in
      the density of tyrosine hydroxylase immunoreactivity in all layers of the dorsal
      anterior cingulate cortex. This was followed by a sustained period in which
      immunoreactivity in the supragranular layers returned to levels that were just
      below normal (between 72 and 79% of normal), and labeling in deep laminae
      stabilized at considerably elevated innervation densities (approximately 150% of
      normal). Neither the acute decrease nor the chronic over-innervation
      characteristic of gonadectomized animals was observed in rats that were
      gonadectomized and supplemented with testosterone proprionate. Open field
      activity assessed along a corresponding 10 week timeline showed that
      gonadectomized animals were significantly less active than hormonally intact
      controls, a behavioral pattern opposite to the hyperactivity which persists
      following prefrontal dopamine lesions. Gonadectomized animals supplemented with
      testosterone proprionate, on the other hand, had open field scores that were not
      significantly different from controls. Taken together, these findings indicate
      that the adult hormone environment provides a significant, and seemingly
      functionally significant influence over the catecholamine innervation of the rat
      prefrontal cortex. Such lifelong responsiveness of the prefrontal cortical
      catecholamines to circulating hormones suggests that gonadal steroids are an
      active component of the biology of normal adult cognition, and may also have
      relevance for cortical dysfunction in disorders such as schizophrenia which are
      not only strongly tied to the catecholamines, but exhibit considerable biases
      among men and women as well.

PMID- 10199627
TI  - Sex and seasonal differences in the rate of cell proliferation in the dentate
      gyrus of adult wild meadow voles.
AB  - In order to study the neurobiological basis of seasonal changes in hippocampal
      structure and function, the rate of cell proliferation was examined in male and
      female wild meadow voles captured during different seasons. We found that the
      number of [3H]thymidine-labeled cells varied across the seasons and across sex in
      the meadow vole. Non-breeding female meadow voles had a higher rate of cell
      proliferation and cell death than males captured during either season or breeding
      females. These seasonal changes in the female meadow vole were associated with
      both fluctuating levels of adrenal steroids and gonadal steroids. Estradiol level
      was highly correlated with both the number of [3H]thymidine-labeled cells and the
      number of pyknotic cells in female meadow voles, with high levels of estradiol
      being associated with low levels of cell proliferation and cell death.
      Corticosterone level was associated with the number of [3H]thymidine-labeled
      cells in the hilus of female meadow voles. This seasonal change in the number of
      [3H]thymidine-labeled cells was also related to the overall volume of the
      hippocampus. At variance with past literature, there was no statistically
      significant sex difference favoring males in hippocampal volume, although the
      means were in the predicted direction. In male meadow voles, the number of
      pyknotic cells was related to testosterone level, with high levels of
      testosterone being associated with greater levels of cell death in the granular
      cell layer. There was also a suggestion that the number of [3H]thymidine-labeled
      cells in the hilus varied seasonally in males, with higher rates of cell
      proliferation during the breeding season than during the non-breeding season. In
      summary, we found that there were large fluctuations across the season in the
      rate of cell proliferation in the dentate gyrus of adult female meadow voles.
      Females captured during the non-breeding season had higher rates of cell
      proliferation in the granule cell layer than females captured during the breeding
      season. This seasonal fluctuation was related to hormone levels, with high levels
      of corticosterone and estradiol being related to lower levels of cell
      proliferation. These seasonal changes in cell proliferation may be related to
      known changes in spatial learning in the meadow vole and provide insights into
      changes in the hippocampus that occur in other species, including primates.

PMID- 10199628
TI  - Strain differences in Fos expression following airpuff startle in Spontaneously
      Hypertensive and Wistar Kyoto rats.
AB  - The airpuff startle stimulus elicits both a behavioral and a concurrent
      sympathetic and parasympathetic activation, which have been shown to differ
      between inbred normotensive Wistar Kyoto and Spontaneously Hypertensive rat
      strains. Neither the brain sites responsible for the cardiovascular and motor
      responses, nor the origins of the strain differential responses, have yet been
      elucidated. The goals of the present study were (i) to define the neuronal
      pattern of immunoreactive Fos expression to the airpuff stimulus, and (ii) to
      determine whether this pattern of expression differed between the two contrasting
      inbred rat strains, thereby relating to observed differences in response. The
      airpuff stimulus induced Fos protein expression in discrete nuclei within the
      hypothalamus, thalamus, midbrain, pons and medulla of both strains, with strain
      dependent differences evident in the hypothalamus (lateral, ventromedial and
      dorsomedial), pons (locus coeruleus) and medulla (rostroventrolateral medulla and
      solitary tract nuclei). To remove Fos expression arising from test chamber
      novelty, which was observed in both strains, a subset of animals was habituated
      to the test chamber for four days prior to testing. Habituation reduced Fos
      expression in several brain regions in the Wistar Kyoto, but failed to do so in
      the Spontaneously Hypertensive rat. The present results are the first to identify
      a set of brain regions likely to be responsible for the mediation of the
      cardiovascular and motor responses associated with the airpuff startle stimulus.
      Several of the identified areas contain neurotransmitters implicated by prior
      pharmacological studies. Further, these data identify differences in the degree
      of activation of specific neuronal structures that probably underlie strain
      differences in the cardiovascular response to the airpuff. Additionally, the
      results provide a cellular correlate to reported deficits in behavioral
      habituation by the Spontaneously Hypertensive rat and suggest a potentially
      profound difference between the ability of these two strains to adapt to repeated
      mild stress stimuli.

PMID- 10199629
TI  - Modulation of desensitization at glutamate receptors in isolated crucian carp
      horizontal cells by concanavalin A, cyclothiazide, aniracetam and PEPA.
AB  - In horizontal cells freshly dissociated from crucian carp (Carassius auratus)
      retina, we examined the effects of modulators of glutamate receptor
      desensitization, concanavalin A, cyclothiazide, aniracetam and 4-[2
      (phenylsulfonylamino)ethylthio]-2,6-difluoro-phenoxyacetam ide (PEPA), on
      responses to rapid application of glutamate and kainate, using whole-cell voltage
      clamp techniques. Incubation of concanavalin A suppressed the peak response but
      weakly potentiated the equilibrium response of horizontal cells to glutamate.
      Cyclothiazide blocked glutamate-induced desensitization in a dose-dependent
      manner, which resulted in a steady increase of the equilibrium current. The
      concentration of cyclothiazide causing a half-maximal potentiation for the
      equilibrium response was 85 microM. Furthermore, cyclothiazide shifted the dose
      response relationship of the equilibrium current to the right, but slightly
      suppressed the kainate-induced sustained current. These effects of concanavalin A
      and cyclothiazide are consistent with the supposition that glutamate receptors of
      carp horizontal cells may be an alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionate (AMPA)-preferring subtype. In order to further characterize the AMPA
      receptors of horizontal cells, modulation by aniracetam and PEPA of glutamate-
      and kainate-induced currents was studied. Aniracetam, a preferential modulator of
      flop variants of AMPA receptors, considerably blocked desensitization of
      glutamate-induced currents, but only slightly potentiated kainate-induced
      currents. It was further found that PEPA, a flop-preferring allosteric modulator
      of AMPA receptor desensitization, slightly suppressed the peak current, while it
      dramatically potentiated the equilibrium current induced by glutamate in a dose
      dependent manner. PEPA was much potent than aniracetam at these receptors and
      showed the effect on glutamate-induced desensitization even at a concentration as
      low as 3 microM. PEPA also potentiated non-desensitizing currents induced by
      kainate, but with much less extent. These modulatory effects of concanavalin A,
      cyclothiazide, aniracetam and PEPA on AMPA receptors in carp horizontal cells
      were rather similar to those obtained at AMPA receptors assembled from flop
      variants expressed in Xenopus oocyte and HEK cell. Consequently, we speculate
      that the AMPA receptor on carp horizontal cells may predominantly carry the flop
      splice variants.

PMID- 10199630
TI  - Rapid desensitization of PC12 cells stimulated with high concentrations of
      extracellular S100.
AB  - Undifferentiated PC12 cells undergo apoptosis, via a calcium-induced calcium
      release mechanism, when the calcium-binding protein purified from bovine brain
      (native S100) is present in micromolar concentration in the medium. This process
      begins when S100 binds to specific membrane binding sites and involves up to 50%
      of the cell population. In the experiments reported here, we demonstrate that, by
      utilizing [3H]S100, the S100 protein can be displaced from its binding sites only
      during the first 10 min of incubation. This fact is due to an internalization
      mechanism, having a time-course with a plateau after 10-20 min of incubation. The
      native form of S100 is a mixture of two different S100 isoforms: S100A1 (20%) and
      S100B (80%). Using confocal microscopy and monoclonal antibodies, we demonstrated
      that only one of these isoforms, S100A1, was autoexpressed in more than 50% of
      the PC12 cells analysed. After cell incubation with 2 microM native S100, S100B
      also appears in PC12 cells, with a maximum presence after 10 min of incubation.
      This fact seems to indicate that this isoform, at least, is effectively
      translocated when stimulated with external native S100. From the data reported,
      it is possible to hypothesize that, in PC12 cells, a possible homeostatic
      mechanism is present that can counteract the effect of a continuously applied
      lethal stimulus (stimuli) on cell viability.

PMID- 10199631
TI  - Heat-shock protein protection.

PMID- 10199632
TI  - Using spontaneous and induced mutations to dissect brain and behavior
      genetically.

PMID- 10199633
TI  - Characterizing complex chemosensors: information-theoretic analysis of olfactory
      systems.
AB  - The mechanisms that underlie a wine lover's ability to identify a favorite
      vintage and a dog's ability to track the scent of a lost child are still deep
      mysteries. Our understanding of these olfactory phenomena is confounded by the
      difficulty encountered when attempting to identify the parameters that define
      odor stimuli, by the broad tuning and variability of neurons in the olfactory
      pathway,and by the distributed nature of olfactory encoding. These issues pertain
      to both biological systems and to newly developed 'artificial noses' that seek to
      mimic these natural processes. Information theory, which quantifies explicitly
      the extent to which the state of one system (for example, the universe of all
      odors) relates to the state of another (for example, the responses of an odor
      sensing device),can serve as a basis for analysing both natural and engineered
      odor sensors. This analytical approach can be used to explore the problems of
      defining stimulus dimensions, assessing strategies of neuronal processing, and
      examining the properties of biological systems that emerge from interactions
      among their complex components. It can also serve to optimize the design of
      artificial olfactory devices for a variety of applications, which include process
      control, medical diagnostics and the detection of explosives.

PMID- 10199634
TI  - Neurotrophic factors.

PMID- 10199635
TI  - Sight and insight--on the physiological role of nitric oxide in the visual
      system.
AB  - Research in the fields of cellular communication and signal transduction in the
      brain has moved very rapidly in recent years. Nitric oxide (NO) is one of the
      latest discoveries in the arena of messenger molecules. Current evidence
      indicates that, in visual system, NO is produced in both postsynaptic and
      presynaptic structures and acts as a neurotransmitter, albeit of a rather
      unorthodox type. Under certain conditions it can switch roles to become either
      neuronal 'friend' or 'foe'. Nitric oxide is a gas that diffuses through all
      physiological barriers to act on neighbouring cells across an extensive volume on
      a specific time scale. It, therefore,has the opportunity to control the
      processing of vision from the lowest level of retinal transduction to the control
      of neuronal excitability in the visual cortex.

PMID- 10199636
TI  - The TINS Lecture. Understanding the roles of Otx1 and Otx2 in the control of
      brain morphogenesis.
AB  - The murine homologs of the orthodenticle (otd) gene of Drosophila, Otx1 and Otx2,
      have an important role in brain morphogenesis. Analysis of Otx1 and Otx2 null
      mice reveals that Otx1 is required primarily for corticogenesis and sense-organ
      development,while Otx2 is necessary for specification and maintenance of anterior
      neural plate as well as for proper gastrulation. Cross-phylum recoveries of Otx1
      abnormalities by Drosophila otd, and vice versa, indicate that genetic functions
      required in mammalian-brain development evolved in a primitive ancestor of flies
      and mice. Knock-in mouse models in which Otx2 was replaced with Otx1, and vice
      versa, provide evidence that the existence of Otx1-/- and Otx2-/- divergent
      phenotypes largely reflects differences in expression patterns rather than in the
      biochemical activity of OTX1 and OTX2. In evolutionary terms, some of these
      findings lead us to hypothesize a fascinating and crucial role for Otx genes that
      contributes to the genetic program required for the specification of the
      development of the vertebrate head.

PMID- 10199637
TI  - Does the right side know what the left is doing?
AB  - Following peripheral-nerve lesions there are well-documented events that affect
      the contralateral nonlesioned structures. These contralateral effects are
      qualitatively similar to those occurring at the ipsilateral side, but are usually
      smaller in magnitude and have a briefer time course. It is unclear whether the
      findings are an epiphenomenon or serve a biological purpose, but in either case
      the existence of these effects implies the presence of unrecognized signalling
      mechanisms that link the two sides of the body. Strong circumstantial evidence
      argues against a peripheral mechanism (for example, via circulating factors) and
      in favour of a central mechanism, in particular signalling via the system of
      commissural interneurons that is present in spinal cord and brainstem. While an
      altered pattern of activity in this system might underlie the phenomenon, there
      are several reasons for proposing that the changes depend upon chemical signals,
      possibly growth factors. Because of its relative easy access for experimental
      manipulation, the spinal cord could serve as a model system to study these
      transmedian signalling systems.

PMID- 10199638
TI  - Maps versus clusters: different representations of auditory space in the midbrain
      and forebrain.
AB  - The auditory system determines the location of stimuli based on the evaluation of
      specific cues. The analysis begins in the tonotopic pathway, where these cues are
      processed in parallel, frequency-specific channels. This frequency-specific
      information is processed further in the midbrain and in the forebrain by
      specialized, space-processing pathways that integrate information across
      frequency channels, creating high-order neurons tuned to specific locations in
      space. Remarkably, the results of this integrative step are represented very
      differently in the midbrain and forebrain: in the midbrain, space is represented
      in maps, whereas, in the forebrain, space is represented in clusters of similarly
      tuned neurons. We propose that these different representations reflect the
      different roles that these two brain areas have in guiding behavior.

PMID- 10199639
TI  - Where the abstract feature maps of the brain might come from.
AB  - Three types of neuronal organization can be called 'brain maps': sets of feature
      sensitive cells, ordered projections between neuronal layers and ordered maps of
      abstract features. The latter are most intriguing as they reflect the central
      properties of an organism's experiences and environment. It is proposed that such
      feature maps are learned in a process that involves parallel input to neurons in
      a brain area and adaptation of neurons in the neighborhood of the cells that
      respond most strongly to this input. This article presents a new mathematical
      formulation for such adaptation and relates it to physiological functions.

PMID- 10199640
TI  - Callosal disconnection syndrome in a left-handed patient due to infarction of the
      total length of the corpus callosum.
AB  - We report on a left-handed patient with an ischemic infarction affecting
      exclusively the total length of the corpus callosum. This lesion clinically
      correlated with an almost complete callosal disconnection syndrome as described
      in callosotomy subjects, including unilateral verbal anosmia, hemialexia,
      unilateral ideomotor apraxia, unilateral agraphia, unilateral tactile anomia,
      unilateral constructional apraxia, lack of somesthetic transfer and dissociative
      phenomena. Despite the patient's left-handedness, his pattern of deficits was
      similar to the disconnection syndrome found in right-handers. Our report focusses
      on motor dominance and praxis. We followed-up the improvement in left apraxia and
      investigated the ability to initiate and learn a new visuo-motor skill. The
      results permit two tentative assumptions: (1) that the improvement in left
      apraxia was due to a compensatory increase in ipsilateral proximal muscle
      control, and (2) that motor dominance, i.e. the competence to initiate and learn
      a new movement pattern, was hemispherically dissociable from manual dominance in
      the sense of praxis control.

PMID- 10199641
TI  - Spatial representation in the normal visual field: a study of hemifield line
      bisection.
AB  - We examined bisection of lines viewed in only one hemifield by normal subjects.
      Subjects first performed a traditional version of line bisection, by indicating
      the perceived midpoint of a line on paper with a penmark. Bisection was accurate
      when they were allowed to shift their gaze over the stimulus, but it was biased
      towards the central visual field (centripetally) when gaze was fixed so that the
      line was seen in only one hemifield. In a second experiment, lines with
      transectors at various locations were presented briefly on a screen and subjects
      had to indicate on which side of the perceived midpoint the transector was
      located. A centripetal bias was still found, indicating that it has a perceptual
      origin. The interaction between bias and effects of tangent line presentation
      suggested that subjects were performing an angle bisection rather than a line
      bisection. Also, there was bias in not only right and left hemifields but also
      upper and lower hemifields. In a third experiment, increasing the width of the
      stimulus bars peripherally did not eliminate this bias. Bias was size-invariant
      along the horizontal meridian. This spatial version of Weber's law was modeled by
      a magnification function using an exponential equation. The slope of this
      function is much shallower than those currently known for V1, V4 and V5. We
      conclude that a centripetal bias exists for hemifield line bisection and that
      this bias likely contributes to the contralateral bias of line bisection by
      hemianopic patients found in other studies.

PMID- 10199642
TI  - The bare bones of object recognition: implications from a case of object
      recognition impairment.
AB  - Three experiments were designed to investigate the performance of a patient (RK)
      who could name objects when presented in conventional views but showed
      catastrophic failures in identification from unconventional views. The aim of all
      three experiments was to assess the properties of the central representations
      that allow recognition of objects presented in conventional but not
      unconventional views. All three experiments showed that RK had problems in object
      identification not apparent from his naming performance. In the first experiment,
      RK was found to be extremely impaired at recognising the parts of objects even
      though he could name the whole object. In the second experiment, alterations in
      colour, shape and parts of objects were undetected in stimuli that he could name.
      In the third experiment, RK showed considerable difficulty with mirror-images and
      inversion tasks. The explanation for RK's impaired object recognition could not
      be attributed to defects to his early visual processing. We argue that RK's
      recognition is achieved through abstract (object-centred) representations that
      are global rather than local, and quite independent of their spatial framework.
      These abstract representations we take to be the essential bare bones for object
      recognition.

PMID- 10199643
TI  - Word and picture matching: a PET study of semantic category effects.
AB  - We report two positron emission tomography (PET) studies of cerebral activation
      during picture and word matching tasks, in which we compared directly the
      processing of stimuli belonging to different semantic categories (animate and
      inanimate) in the visual (pictures) and verbal (words) modality. In the first
      experiment, brain activation was measured in eleven healthy adults during a
      same/different matching task for textures, meaningless shapes and pictures of
      animals and artefacts (tools). Activations for meaningless shapes when compared
      to visual texture discrimination were localized in the left occipital and
      inferior temporal cortex. Animal picture identification, either in the comparison
      with meaningless shapes and in the direct comparison with non-living pictures,
      involved primarily activation of occipital regions, namely the lingual gyrus
      bilaterally and the left fusiform gyrus. For artefact picture identification, in
      the same comparison with meaningless shape-baseline and in the direct comparison
      with living pictures, all activations were left hemispheric, through the
      dorsolateral frontal (Ba 44/6 and 45) and temporal (Ba 21, 20) cortex. In the
      second experiment, brain activation was measured in eight healthy adults during a
      same/different matching task for visually presented words referring to animals
      and manipulable objects (tools); the baseline was a pseudoword discrimination
      task. When compared with the tool condition, the animal condition activated
      posterior left hemispheric areas, namely the fusiform (Ba 37) and the inferior
      occipital gyrus (Ba 18). The right superior parietal lobule (Ba 7) and the left
      thalamus were also activated. The reverse comparison (tools vs animals) showed
      left hemispheric activations in the middle temporal gyrus (Ba 21) and precuneus
      (Ba 7), as well as bilateral activation in the occipital regions. These results
      are compatible with different brain networks subserving the identification of
      living and non-living entities; in particular, they indicate a crucial role of
      the left fusiform gyrus in the processing of animate entities and of the left
      middle temporal gyrus for tools, both from words and pictures. The activation of
      other areas, such as the dorsolateral frontal cortex, appears to be specific for
      the semantic access of tools only from pictures.

PMID- 10199644
TI  - Free-viewing perceptual asymmetries for the judgement of brightness, numerosity
      and size.
AB  - Perceptual asymmetries under free-viewing conditions were investigated in 24
      normal dextral adults. Three tasks were administered that required participants
      to chose between a pair of left/right reversed stimuli on the basis of their
      brightness, numerosity or size. These stimulus features were represented
      asymmetrically within the stimuli, so that each stimulus appeared darker, larger
      or more numerous on the left or right sides. Participants more often selected the
      stimulus with the relevant feature on the left-hand side for all three tasks.
      Response times for leftward responses were faster than rightward responses. Split
      half reliabilities revealed a high level of consistency within the tasks.
      However, the correlation between tasks was low. These results suggest that the
      different tasks, while showing similar levels of perceptual asymmetry, engage
      distinct sets of lateralised processes.

PMID- 10199645
TI  - The role of auditory cortex in retention of rhythmic patterns as studied in
      patients with temporal lobe removals including Heschl's gyrus.
AB  - This experiment examined the participation of the auditory cortex of the temporal
      lobe in the perception and retention of rhythmic patterns. Four patient groups
      were tested on a paradigm contrasting reproduction of auditory and visual
      rhythms: those with right or left anterior temporal lobe removals which included
      Heschl's gyrus (HG), the region of primary auditory cortex (RT-A and LT-A); and
      patients with right or left anterior temporal lobe removals which did not include
      HG (RT-a and LT-a). Estimation of lesion extent in HG using an MRI-based
      probabilistic map indicated that, in the majority of subjects, the lesion was
      confined to the anterior secondary auditory cortex located on the anterior
      lateral extent of HG. On the rhythm reproduction task, RT-A patients were
      impaired in retention of auditory but not visual rhythms, particularly when
      accurate reproduction of stimulus durations was required. In contrast, LT-A
      patients as well as both RT-a and LT-a patients were relatively unimpaired on
      this task. None of the patient groups was impaired in the ability to make an
      adequate motor response. Further, they were unimpaired when using a dichotomous
      response mode, indicating that they were able to adequately differentiate the
      stimulus durations and, when given an alternative method of encoding, to retain
      them. Taken together, these results point to a specific role for the right
      anterior secondary auditory cortex in the retention of a precise analogue
      representation of auditory tonal patterns.

PMID- 10199646
TI  - Somatosensory extinction for meaningful objects in a patient with right
      hemispheric stroke.
AB  - Implicit, high level processing of extinguished objects has often been described
      in the visual modality. In the tactile domain, however, research on this topic is
      meagre and it is still uncertain whether processing of tactually presented
      stimuli can be affected by the same attentional disorders as visual stimuli. In
      this paper we describe a patient, ENM, with visual neglect and light touch
      extinction who, in a naming task of objects presented in the tactile modality,
      simultaneously to both hands, showed extinction for left hand objects. He was,
      nevertheless, able to make above chance Same/Different judgements on the two
      stimuli. We also tested two neurologically intact subjects who performed the test
      wearing a ski-glove on the left hand to impair the recognition of left hand
      objects. In these subjects, Same/Different judgements were at chance level when
      recognition rate was as low as that found in patient ENM. This happened when
      either the objects, although sharing the same name were different in shape
      (conditions Same-Different) or when the two objects were different with respect
      to the category name but were actually physically similar (conditions Different
      Similar). However, when the objects were either identical or completely
      different, i.e., in a condition where judgement could be based simply on the
      physical analysis of the object shape (condition Same Identical and Different
      Dissimilar), their Same/Different judgements were above chance, despite the
      tactual deficit. Our conclusion was that patient ENM showed implicit recognition
      of left hand objects, at least in the Same Different and in the Different-Similar
      conditions, whereas, in the same conditions, normal subjects with an artificial
      sensory impairment did not. Our results also show that Same/Different judgements
      may be, in some conditions, less demanding than naming tasks, as suggested by
      Farah et al. Furthermore, patient ENM performed the test both with uncrossed and
      crossed hands. We found that extinction always affected the hand contralateral to
      the brain damage, although there was a tendency for a decrement of the
      ipsilesional hand performance in the crossed condition. We discuss these findings
      with reference to the most recent theories on the existence of a body centered
      spatial frame of reference.

PMID- 10199647
TI  - Covert orienting and focusing of attention in children with attention deficit
      hyperactivity disorder.
AB  - Performance on the covert visuo-spatial attentional functions of orienting and
      focusing by a group of ADHD children (n = 20) was compared to that of age and sex
      matched control children. In Experiment 1, responses were given to cued targets
      at valid and invalid locations. In Experiment 2, responses were given to targets
      presented in small, medium-sized or large visual field locations. For both
      experiments, the hypotheses that reaction times of ADHD children would be greater
      than those of control children and that performance would be asymmetrical, were
      supported. For Experiment 1, ADHD children showed bilaterally greater 'benefits'
      from having directed attention to the cued location and greater 'costs' in having
      to relocate the attentional focus than controls. In Experiment 2, the hypothesis
      that the function of focusing attention by ADHD children may show breakdown in
      the usual pattern of an increase in reaction time with focus area was partly
      supported by the finding of similar reaction times to targets presented in medium
      sized and large regions of the left visual hemifield. These results have been
      interpreted as reflecting a stronger anchorage of attention by ADHD children upon
      a cued location and an inability to shift covert attention easily to an
      alternative location. The breakdown of the focusing function suggests adoption of
      similar time response sets across focus area size by the more compromised right
      hemisphere.

PMID- 10199648
TI  - Does auditory attention shift in the direction of an upcoming saccade?
AB  - In a series of experiments, we examined whether auditory attention shifts in the
      direction of an upcoming saccade, as recently reported for visual attention.
      Normal listeners made speeded discriminations for the elevation (up versus down)
      of abrupt sounds, regardless of their laterality. Each sound was presented around
      the time that a lateral saccade was made. Auditory elevation discriminations were
      reliably faster when the saccade was made towards the side of the auditory probe
      rather than away. Furthermore, an auditory probe on one side speeded up centrally
      cued saccades made in that direction, although sounds did not influence saccades
      to peripheral visual events. The latter visual events were insufficient to affect
      hearing unless a saccade was made towards them. A further study showed that
      fixating towards or away from sounds, rather than saccading, could also affect
      elevation judgements, with poorer performance when fixating away. However, the
      influence of an upcoming saccade upon hearing could not be reduced to this
      fixation effect, since the saccade influence was found even for sounds which
      terminated before any shift in fixation began. Taken together, our results imply
      that the direction of an upcoming saccade can affect hearing, as can eye
      position.

PMID- 10199649
TI  - Asymmetries between dominant and non-dominant hands in real and imagined motor
      task performance.
AB  - Motor imagery is a dynamic state in which an individual mentally simulates the
      performance of a specific motor action or motor task. Recent behavioural and
      neuroimaging evidence suggests that the same neurocognitive networks control real
      and imagined movements. This hypothesis was tested by investigating whether motor
      asymmetries related to cerebral dominance also occurred for imagined movements.
      Fifty subjects performed the visually guided pointing task of Sirigu et al.
      [Sirigu, A., Duhamel, J., Cohen, L., Pillon, B., Dubois, B. and Agid, Y., The
      mental representation of hand movements after parietal cortex damage. Science,
      1996, 273, 1564-1567.] using their dominant and non-dominant hands. Analysis of
      group data indicated that both real and imagined movement conformed to Fitts'
      law. Analysis of individual data indicated that asymmetries arising from motor
      dominance in real movements also occurred for imagined movements. However, the
      relative slowing and error associated with the non-dominant hand was greater for
      imagined movements than for real movements. These asymmetries support the
      hypothesis that real and imagined movements are represented within the same
      neurocognitive networks but suggest that asymmetries in performance related to
      handedness are greater for imagined movements. In addition, while the visually
      guided pointing task provides a useful test of the ability to make imagined
      movements, asymmetries in the speed and reliability of imagined performance are
      significantly greater than those for real performance.

PMID- 10199650
TI  - Row blindness in Gestalt grouping and developmental dyslexia.
AB  - A classic Gestalt figure is a 4 x 4 array of items grouped by similarity into
      either rows or columns. We found that some people do not see rows ("row
      blindness"). Furthermore, row blindness correlates with difficulties processing
      written language--more than half of the college-age dyslexics tested were row
      blind. Reading difficulties are probably not a cause of row blindness and forming
      rows by grouping is a part of reading, suggesting that row blindness might be one
      source of problems processing written language.

PMID- 10199651
TI  - Combining hydrophobicity and helicity: a novel approach to membrane protein
      structure prediction.
AB  - In spite of the overwhelming numbers and critical biological functions of
      membrane proteins, only a few have been characterized by high-resolution
      structural techniques. From the structures that are known, it is seen that their
      transmembrane (TM) segments tend to fold most often into alpha-helices. To
      evaluate systematically the features of these TM segments, we have taken two
      approaches: (1) using the experimentally-measured residence behavior of
      specifically designed hydrophobic peptides in RP-HPLC, a scale was derived based
      directly on the properties of individual amino acids incorporated into membrane
      interactive helices: and (2) the relative alpha-helical propensity of each of the
      20 amino acids was measured in the organic non-polar environment of n-butanol. By
      combining the resulting hydrophobicity and helical propensity data, in
      conjunction with consideration of the 'threshold hydrophobicity' required for
      spontaneous membrane integration of protein segments, an approach was developed
      for prediction of TM segments wherein each must fulfill the dual requirements of
      hydrophobicity and helicity. Evaluated against the available high-resolution
      structural data on membrane proteins, the present combining method is shown to
      provide accurate predictions for the locations of TM helices. In contrast, no
      segment in soluble proteins was predicted as a 'TM helix'.

PMID- 10199652
TI  - Molecular modeling, synthesis, and structures of N-methylated 3,5-linked pyrrolin
      4-ones toward the creation of a privileged nonpeptide scaffold.
AB  - The molecular modeling, synthesis, and elucidations of the solid state and
      solution structures of N-methylated 3,5-linked bispyrrolin-4-ones are described.
      Prior investigations established that the 3,5-linked pyrrolin-4-one based
      scaffold can be incorporated into mimics of beta-sheet/beta-strands and into
      potent, orally bioavailable inhibitors of the HIV-1 protease. To extend the
      utility of this scaffold beyond that of the initially designed mimics of beta
      sheet/beta-strands, we have now explored the structure of N-methylated
      pyrrolinones. Molecular modeling indicated that N-methylated bispyrrolinones
      could adopt three low-energy backbone conformations (ca. 165 degrees, 289
      degrees, and 320 degrees). Upon their successful synthesis, structural
      elucidation both in the solid state and in solution revealed the existence of two
      of the three predicted backbone conformers (ca. 165 degrees and 289 degrees). Two
      structures were particularly noteworthy and completely unexpected. Mono-N-methyl
      bispyrrolinone (+)-1 self assembled in the solid state to form a novel helix,
      while the acetylene-linked dimer of (+)-1, designed to potentiate the observed
      helical array, instead associated via an intermolecular hydrogen bond in parallel
      columns. These serendipitous observations led us to speculate that the
      pyrrolinone moiety may in fact represent a privileged nonpeptide scaffold, able
      to mimic not only the extended beta-sheet/beta-strand conformation as initially
      targeted, but also diverse conformations including those analogous to beta-turns
      and helices. These seemingly unlimited conformations greatly expand the scope of
      this scaffold for the development of low-molecular weight ligands for
      biologically important macromolecules.

PMID- 10199653
TI  - Design of proteins using rigid organic macrocycles as scaffolds.
AB  - We have designed and synthesized new three-helix template-assembled synthetic
      proteins (TASPs) 1a-c. The template was the rigid cyclotribenzylene (CTB)
      macrocycle 2, which has C3 symmetry. Thiol moieties on the CTB template were used
      to link cysteine-containing peptide strands 3a-c via disulfide bonds. With
      designed peptide strands of 15 and 18 residues in length, the structure of TASPs
      1a-c were determined to be helical in water according to circular dichroism (CD)
      spectroscopy. The helicities of TASPs 1a-c were unchanged over large ranges of pH
      (2-12) and salt concentrations (0-2 M KCl). TASPs 1a-c were also extremely
      resistant to chemical denaturants: it requires a guanidine hydrochloride (GnHCl)
      concentration of 7.4 M for TASPs 1a-c to lose 50% of their helicity. The major
      force for stabilization of TASPs 1a-c is the hydrophobic bundling of the helices.

PMID- 10199654
TI  - Two new beta-strand mimics.
AB  - In a previous report, Nowick and co-workers described beta-strand mimic A, which
      duplicates the structure and hydrogen-bonding pattern of one edge of a
      tetrapeptide in a beta-strand conformation (Nowick, J. S.; Pairish, M.; Lee, I.
      Q.; Holmes, D. L.; Ziller, J. W. J. Am. Chem. Soc. 1997, 119, 5413). Beta-strand
      mimic A is composed of a 5-amino-2-methoxybenzoic acid unit linked to a 5
      hydrazino-2-methoxybenzamide unit by means of an acylhydrazine group. This paper
      introduces two related beta-strand mimics (B and C) and reports their comparison
      to beta-strand mimic A. Beta-strand mimic B is composed of a 5-amino-2
      methoxybenzoic acid unit linked by a diacylhydrazine group to a fumaramide unit;
      beta-strand mimic C is composed of a 5-amino-2-methoxybenzoic acid unit linked by
      a diacylhydrazine group to a peptide. Beta-strand mimics A-C were connected to
      tripeptide (Phe-Ile-Leu) groups by means of 1,2-diaminoethane diurea turn units
      to form artificial beta-sheets 1-3. 1H NMR studies, involving ROESY, chemical
      shift, coupling constant, and variable temperature experiments, reveal that 1-3
      adopt hydrogen-bonded antiparallel beta-sheet conformations and establish that
      all three templates are viable beta-strand mimics.

PMID- 10199655
TI  - The nucleation of monomeric parallel beta-sheet-like structures and their self
      assembly in aqueous solution.
AB  - The aromatic diacid residue 4,6-dibenzofuranbispropionic acid (1) was designed to
      nucleate a parallel beta-sheet-like structure in small peptides in aqueous
      solution via a hydrogen-bonded hydrophobic cluster. Even though a 14-membered
      ring hydrogen bond necessary for parallel beta-sheet formation is favored in
      simple amides composed of 1, this hydrogen bonding interaction does not appear to
      be sufficient to nucleate parallel beta-sheet formation in the absence of
      hydrophobic clustering between the dibenzofuran portion of 1 and the hydrophobic
      side chains of the flanking alpha-amino acids. The subsequence --hydrophobic
      residue-1-hydrophobic residue-- is required for folding in the context of a
      nucleated two-stranded parallel beta-sheet structure. In all cases where the
      peptidomimetics can fold into two diastereomeric parallel beta-sheet structures
      having different hydrogen bonding networks, these conformations appear to
      exchange rapidly. The majority of the parallel beta-sheet structures evaluated
      herein undergo linked intramolecular folding and self-assembly, affording a
      fibrillar beta-sheet quaternary structure. To unlink folding and assembly,
      asymmetric parallel beta-sheet structures incorporating N-methylated alpha-amino
      acid residues have been synthesized using a new solid phase approach. Residue 1
      facilitates the folding of several peptides described within affording a
      monomeric parallel beta-sheet-like structure in aqueous solution, as ascertained
      by a variety of spectroscopic and biophysical methods, increasing our
      understanding of parallel beta-sheet structure.

PMID- 10199656
TI  - Structure-function relationship in a beta-sheet peptide inhibitor of E47
      dimerization and DNA binding.
AB  - A beta-sheet peptide inhibitor, 2H10, has been developed that inhibits the
      dimerization of the transcription factor E47. Inhibition of E47 dimerization has
      been demonstrated to also inhibit the DNA binding of this transcription factor.
      Truncated peptides based on 2H10 have demonstrated that the beta-sheet content of
      these peptides directly correlates with their inhibitory properties. Individual
      residues within 2H10 were identified that were responsible for the beta-sheet
      secondary structure by employing an alanine replacement strategy. The beta-sheet
      character of the alanine mutants also correlated well with their inhibition of
      E47 DNA binding. These results provide further evidence that interactions between
      the interfacial peptide inhibitors of E47 and the transcription factor itself are
      mediated by a beta-sheet structure.

PMID- 10199657
TI  - Alcohol-induced denaturation of beta-lactoglobulin: a close correlation to the
      alcohol-induced alpha-helix formation of melittin.
AB  - Alcohols denature the native structure of proteins and induce alpha-helical
      structure. The potential of alcohols causing such effects varies substantially
      depending on the alcohol species. With beta-lactoglobulin as a model protein, we
      compared the effects of various alcohols and observed the additive contribution
      of each group constituting the alcohol molecules. Whereas the hydrophobic
      hydrocarbon group promotes the transition according to their size, hydrophilic
      hydroxyl group suppresses the transition. Halogen groups promote the transition
      depending on their type and number. It has been known that alcohols induce the
      alpha-helical structure on the short peptides such as melittin. There is a close
      correlation between the potentials of alcohol in denaturing beta-lactoglobulin
      and those in inducing the helical structure in melittin, indicating that the
      underlying mechanisms of the two phenomena are the same.

PMID- 10199658
TI  - Induction of protein-like molecular architecture by self-assembly processes.
AB  - One of the most intriguing self-assembly processes is the folding of peptide
      chains into native protein structures. We have developed a method for building
      protein-like structural motifs that incorporate sequences of biological interest.
      A lipophilic moiety is attached onto an N(alpha)-amino group of a peptide chain,
      resulting in a 'peptide-amphiphile'. The alignment of amphiphilic compounds at
      the lipid solvent interface is used to facilitate peptide alignment and structure
      initiation and propagation. Peptide-amphiphiles containing potentially triple
      helical structural motifs have been synthesized. The resultant head group
      structures have been characterized by circular dichroism and NMR spectroscopies.
      Evidence for a self-assembly process of peptide-amphiphiles has been obtained
      from: (a) circular dichroism spectra and melting curves characteristic of triple
      helices, (b) one- and two-dimensional NMR spectra indicative of stable triple
      helical structure at low temperatures and melted triple-helices at high
      temperatures, and (c) pulsed-field gradient NMR experiments demonstrating
      different self-diffusion coefficients between proposed triple-helical and non
      triple-helical species. The peptide-amphiphiles described here provide a simple
      approach for building stable protein structural motifs using peptide head groups.

PMID- 10199659
TI  - Designed four-helix bundle catalysts--the engineering of reactive sites for
      hydrolysis and transesterification reactions of p-nitrophenyl esters.
AB  - Four-helix bundle proteins have been designed that catalyze the hydrolysis and
      transesterification reactions of p-nitrophenyl esters by a cooperative
      nucleophilic and general acid mechanism. The catalysts consist of two 42-residue
      peptides that fold into helix-loop-helix motifs and dimerise. They have
      previously been shown to recognize anionic and hydrophobic substrates and to
      follow saturation kinetics. The catalytic entity is a HisH(+)-His pair in a
      helical segment spaced i, i+4, which can be supplemented by arginines and lysines
      in the adjacent helix. The binding residues have now been optimized for the
      catalysis of mono-p-nitrophenyl fumarate hydrolysis and found to vary with the
      location of the site. The catalytic efficiency of the HisH(+)-His site in helix
      II in positions 30 and 34 is enhanced by the introduction of arginine and or
      lysine residues in positions 11 and 15, but not in 8 and 11 or in 15 and 19. The
      most efficient catalyst using this site, JNIIR11K15, catalyses the reaction with
      a second-order rate constant of 0.134 M(-1) s(-1) in aqueous solution at pH 5.1
      and 290 K. The second-order rate constant is larger than those of the
      corresponding sites with 'longer' and 'shorter' binding residues. Similar
      experiments have shown that the efficiency and selectivity of catalysts based on
      a HisH(+)-11-His-15 site in helix I are enhanced the most by the introduction of
      Lys-30 and Arg-34.

PMID- 10199660
TI  - Beta-hairpin and beta-sheet formation in designed linear peptides.
AB  - Recent knowledge about the determinants of beta-sheet formation and stability has
      notably been improved by the structural analysis of model peptides with beta
      hairpin structure in aqueous solution. Several experimental studies have shown
      that the turn region residues can not only determine the stability, but also the
      conformation of the beta-hairpin. Specific interstrand side-chain interactions,
      hydrophobic and polar, have been found to be important stabilizing interactions.
      The knowledge acquired in the recent years from peptide systems, together with
      the information gathered from mutants in proteins, and the analysis of known
      protein structures, has led to successful design of a folded three-stranded
      monomeric beta-sheet structure.

PMID- 10199661
TI  - Stereochemical control of peptide folding.
AB  - Stereochemically constrained amino acid residues that strongly favour specific
      backbone conformations may be used to nucleate and stabilize specific secondary
      structures in designed peptides. An overview of the use of alphaalpha-dialkyl
      amino acids in stabilizing helical structures in synthetic peptides is presented,
      with an emphasis on work carried out in the authors laboratory. Alpha
      aminoisobutyric acid (Aib) and related achiral homologs facilitate stable helix
      formation in oligopeptides as exemplified by a large number of crystal structure
      determinations in the solid state. The ability to design conformationally rigid
      helical modules has been exploited in attempts to design structurally well
      characterized helix-linker helix, using potential nonhelical linking segments.
      Beta-hairpin design has been approached by exploiting the tendency of 'prime
      turns' to nucleate hairpin formation. The use of nucleating (D)Pro-Gly segments
      has resulted in the generation of several well characterized beta-hairpin
      structures, including the crystallographic observation of beta-hairpin in a
      synthetic apolar octapeptide. Extensions of this approach to three stranded beta
      sheets and larger structures containing multiple (D)Pro-Gly segments appear
      readily possible.

PMID- 10199662
TI  - Determining the occurrence of a 3(10)-helix and an alpha-helix in two different
      segments of a lipopeptaibol antibiotic using TOAC, a nitroxide spin-labeled
      C(alpha)-tetrasubstituted alpha-aminoacid.
AB  - Trichogin GA IV is a 11-residue lipopeptaibol antibiotic exhibiting membrane
      modifying properties. We synthesized step-by-step by solution methods three
      trichogin analogues, each with a double Aib (alpha-aminoisobutyric acid)-->TOAC
      (2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid) replacement. The
      strict similarity in the conformational propensities of Aib and TOAC allowed us
      to exploit these analogues in a detailed investigation of the conformation of
      this lipopeptaibol in different organic solvents and in a membrane-mimetic
      environment using in particular the double spin labeling ESR technique. We
      conclude that the secondary structure in solution remains essentially unchanged
      if compared to that previously found in the crystal state for trichogin. More
      specifically, the N-terminal region of the peptide folds in a 3(10)-helix, while
      the central and C-terminal regions are mainly alpha-helical. An additional,
      significant proof for the modest plasticity of the trichogin structure was
      obtained by an X-ray diffraction analysis of the nOct-[TOAC4,8, Leu-OMe11]
      analogue. For the three analogues permeability measurements revealed membrane
      modifying properties comparable to those of natural trichogin.

PMID- 10199663
TI  - Vibrational circular dichroism spectroscopy of selected oligopeptide
      conformations.
AB  - Vibrational circular dichroism (VCD) has been shown to be a useful technique for
      characterization of the qualitative secondary structure type for linear
      polypeptides and oligopeptides. A brief review of characteristic spectral
      responses and applications is given. Since VCD is dependent on relatively short
      range interactions, it detects residual structure in such oligomers even if long
      range order is lost. VCD studies presented here for Lys oligomers as well as Lys
      and Glu polymers as a function of length, salt added and temperature, confirm
      residual local order in these 'random coils'. Comparison to results with Pro
      oligomers, supports an interpretation that these extended structures have a left
      handed twist conformation. The 'coil' VCD is shown to be significantly reduced in
      intensity by temperature increase and by decrease in peptide length. By contrast,
      for partially alpha-helical Ac-(AAKAA)3GY-NH2 oligomers, the spectrum changes to
      the high temperature Lys(n) shape on heating, first losing then gaining
      intensity, indicating an equilibrium shift between structured states, from helix
      to coil (locally ordered) forms. VCD is shown to be a useful technique for
      monitoring local order in otherwise random coil structures.

PMID- 10199664
TI  - C-terminal capping motifs in model helical peptides.
AB  - Solution structures of a series of consensus sequence peptides with N- and C
      terminal capping interactions have been determined by 2-D nuclear magnetic
      resonance spectroscopy and a simulated annealing strategy. All peptides are found
      to be stabilized by a hydrophobic interaction and a capping box structure (SXXE)
      at the N-terminus whereas several different capping motifs are discerned near the
      peptide C-terminus. Among these, the asparagine side chain-backbone main chain
      (i, i-4) capping structure is most stabilizing and highly populated in the
      simulated annealing calculation. A glycine alphaL capping motif stabilizes the
      peptide terminus, which otherwise tends to fray, but this is occupied only a
      fraction of the time in the trial structures determined. Our experimental search
      over several models for a second type of C-terminal capping structure, the so
      called 'Schellman motif', which is seen in native proteins, is unsuccessful,
      indicating this structural element contributes less to oligopeptide stability in
      solution and most probably populates only transiently.

PMID- 10199665
TI  - Triple helical stabilities of guest-host collagen mimetic structures.
AB  - The peptoid Nleu (N-isobutylglycine) has been successfully incorporated into a
      series of collagen mimetics composed of Gly-Pro-Nleu and Gly-Nleu-Pro sequences
      and has been able to maintain triple helices in appropriate structures. The
      achiral trimeric sequence Gly-Nleu-Nleu as a guest sequence in structures such as
      Ac-(Gly-Pro-Hyp)3-(Gly-Nleu-Nleu)3-(Gly-Pro-Hyp)3-NH2 retains triple helicity. As
      an extension of this study, we report, in this paper, on a series of guest-host
      collagen mimetic structures in which Gly-Nleu-Pro sequences are employed as the
      host. The guest sequences for these guest-host structures include Gly-Nleu-Nleu
      and Gly-Nx-Pro sequences where Nx is composed of a variety of alkyl and aralkyl
      peptoid residues. From these guest-host collagen mimetic structures, we are able
      to elucidate the contributions of hydrophobic and steric effects on triple helix
      formation. The Gly-Nleu-Pro sequences have been shown to be effective in inducing
      triple helicity. Conformational characterization of the guest-host collagen
      mimetic structures was established by techniques such as temperature-dependent
      optical rotation measurements and circular dichroism (CD) spectroscopy.

PMID- 10199666
TI  - Synthesis and study of peptides with semirigid i and i + 7 side-chain bridges
      designed for alpha-helix stabilization.
AB  - A search for conformational constraints on the peptide alpha-helical conformation
      indicated that para-substituted amino acid derivatives of a benzene ring might be
      suitable for linking pairs of side chains that are separated by two turns of the
      helix. A 14-residue synthetic, amphiphilic alpha-helical peptide model system has
      been used to study the helix stabilizing effects of a series of four such bridges
      having constitutionally isomeric structures. These bridges were used to link
      positions 3 and 10 of the model peptides. The peptides were synthesized in good
      yield by standard solid-phase methods, including cyclization on the solid
      support. They were then studied for their solution conformations and melting
      behavior by circular dichroism (CD) spectropolarimetry, and for their elution
      behavior on reversed-phase HPLC columns. In aqueous solution and in 50% (v/v)
      trifluoroethanol, the most effective bridge for helix stabilization consisted of
      a 4-(aminomethyl)phenylacetic acid residue (AMPA) linked by amide bonds to the
      side chain functional groups of a (S)-2,3-diaminopropionic acid residue (Dap) in
      position 3 of the model peptide and an aspartic acid residue in position 10. This
      Dap3(AMPA), Asp10 bridge was about as effective as two Lys(i), Asp(i+4) lactam
      bridges incorporated linking residues 3 and 7, and 10 and 14, in the same model
      peptide sequence. This suggests that it is worth about 1 kcal/mol of helix
      stabilization energy.

PMID- 10199667
TI  - Optimization of hydrophobic domains in peptides that undergo transformation from
      alpha-helix to beta-fibril.
AB  - Recent studies on peptide fibrillogenesis by the de novo method as well as
      amyloidogenic proteins including prion proteins and Alzheimer's beta-peptides
      have provided insights into the conformational changes, such as alpha-helix to
      beta-structure, involved in folding and misfolding processes. We have found that
      an exposed hydrophobic nucleation domain at N-terminal causes a structural
      transition of a peptide from alpha-helix to beta-fibril. It became clear that N
      terminal acyl groups of particular lengths in a 2alpha-helix peptide caused the
      peptide to undergo an alpha-to-beta transition. The peptide with the octanoyl
      group (C8-2alpha) showed the highest rate of transformation. The study of the
      designed peptides revealed that these alpha-to-beta transitions were closely
      related to the initial alpha-helix conformation and its stability. Engineering
      peptides that undergo alpha-to-beta transitions are attractive not only to the
      study of pathogenic proteins such as prion proteins, but also to the control of
      self-assembly of peptides, which will lead to the development of peptidyl self
      assembling materials.

PMID- 10199668
TI  - Chemical ligation to obtain proteins comprising helices with individual amino
      acid sequences.
AB  - Development of the strategies for assembling multiple kinds of peptide segments
      would give new possibilities for the de novo design of functional proteins. We
      will introduce our approach for the selective assembly of helical peptide
      segments on a peptide template to give four-helix-bundle proteins comprising
      individual helices.

PMID- 10199669
TI  - Beyond health services research.

PMID- 10199670
TI  - Income inequality and health: pathways and mechanisms.
AB  - The relationship between income and health is well established: the higher an
      individual's income, the better his or her health. However, recent research
      suggests that health may also be affected by the distribution of income within
      society. We outline the potential mechanisms underlying the so-called relative
      income hypothesis, which predicts that an individual's health status is better in
      societies with a more equal distribution of incomes. The effects of income
      inequality on health may be mediated by underinvestment in social goods, such as
      public education and health care; disruption of social cohesion and the erosion
      of social capital; and the harmful psychosocial effects of invidious social
      comparisons.

PMID- 10199671
TI  - Low income, race, and the use of mammography.
AB  - OBJECTIVE: To describe national trends in mammography use by race and income and
      to test whether higher use of mammography among low-income African American women
      than low-income white women can be explained by health insurance coverage, usual
      place of health care, or place of residence. DATA SOURCES/STUDY SETTING: Data
      from five years of the National Health Interview Survey spanning the period 1987
      1994. STUDY DESIGN: Trends in the percentage of women 50-64 years of age with a
      mammogram within the past two years were analyzed by race and income. Data for
      1993-1994 were pooled, and with logistic regression analysis, variation in use of
      recent mammography for low-income women was investigated. Independent variables
      are age, race, family income, education, health insurance coverage, place of
      usual source of health care, metropolitan residence, and geographic region. DATA
      COLLECTION/EXTRACTION METHODS: The National Health Interview Survey is a cross
      sectional national survey conducted by the National Center for Health Statistics.
      Data are collected through household interviews. [Editor's note: in keeping with
      HSR policy, the term black is used to conform to its use in the surveys studied.
      In other references to race, the term African American is used.] PRINCIPAL
      FINDINGS: Among women 50-64 years of age use of recent mammograms increased
      rapidly between 1987 and 1991 for all groups of women, and between 1991 and 1994
      the increases slowed. However, increases between 1991 and 1994 have been more
      rapid among low-income black women than among low-income white women. In 1993
      1994, low-income black women were about one-third more likely than low-income
      white women to report mammography within the past two years. This difference
      could not be explained by health insurance coverage, usual source of health care,
      metropolitan status, or region of residence. CONCLUSIONS: These results, which
      provide some evidence of success for screening programs targeted to the poor,
      raise the question of why low-income black women appear to be to more likely than
      low-income white women to have benefited from recent efforts to promote
      mammography. Continued evaluation of mammography programs focused on women who
      are underserved as well as the monitoring of trends and variations in service use
      by race and income are needed.

PMID- 10199672
TI  - Out-of-pocket health spending by poor and near-poor elderly Medicare
      beneficiaries.
AB  - OBJECTIVE: To estimate out-of-pocket health care spending by lower-income
      Medicare beneficiaries, and to examine spending variations between those who
      receive Medicaid assistance and those who do not receive such aid. DATA SOURCES
      AND COLLECTION: 1993 Medicare Current Beneficiary Survey (MCBS) Cost and Use
      files, supplemented with data from the Bureau of the Census (Current Population
      Survey); the Congressional Budget Office; the Health Care Financing
      Administration, Office of the Actuary (National Health Accounts); and the Social
      Security Administration. STUDY DESIGN: We analyzed out-of-pocket spending through
      a Medicare Benefits Simulation model, which projects out-of-pocket health care
      spending from the 1993 MCBS to 1997. Out-of-pocket health care spending is
      defined to include Medicare deductibles and coinsurance; premiums for private
      insurance, Medicare Part B, and Medicare HMOs; payments for non-covered goods and
      services; and balance billing by physicians. It excludes the costs of home care
      and nursing facility services, as well as indirect tax payments toward health
      care financing. PRINCIPAL FINDINGS: Almost 60 percent of beneficiaries with
      incomes below the poverty level did not receive Medicaid assistance in 1997. We
      estimate that these beneficiaries spent, on average, about half their income out
      of-pocket for health care, whether they were enrolled in a Medicare HMO or in the
      traditional fee-for-service program. The 75 percent of beneficiaries with incomes
      between 100 and 125 percent of the poverty level who were not enrolled in
      Medicaid spent an estimated 30 percent of their income out-of-pocket on health
      care if they were in the traditional program and about 23 percent of their income
      if they were enrolled in a Medicare HMO. Average out-of-pocket spending among fee
      for-service beneficiaries varied depending on whether beneficiaries had Medigap
      policies, employer-provided supplemental insurance, or no supplemental coverage.
      Those without supplemental coverage spent more on health care goods and services,
      but spent less than the other groups on prescription drugs and dental care
      services not covered by Medicare. CONCLUSIONS: While Medicaid provides
      substantial protection for some lower-income Medicare beneficiaries, out-of
      pocket health care spending continues to be a substantial burden for most of this
      population. Medicare reform discussions that focus on shifting more costs to
      beneficiaries should take into account the dramatic costs of health care already
      faced by this vulnerable population.

PMID- 10199673
TI  - Pressures on safety net access: the level of managed care penetration and
      uninsurance rate in a community.
AB  - OBJECTIVE: To examine the effects of managed care penetration and the uninsurance
      rate in an area on access to care of low-income uninsured persons and to compare
      differences in access between low-income insured and uninsured persons across
      these different market areas. DATA SOURCES: Primarily the Community Tracking
      Study household survey. Other market-level data were obtained from the Community
      Tracking Study physician survey, American Hospital Association annual survey of
      hospitals, Area Resource File, HCFA Administrative Data, Bureau of Primary Care
      data on Community Health Centers. STUDY DESIGN: Individuals are grouped based on
      the level of managed care penetration and uninsurance rate in the site where they
      reside. Measures of managed care include overall managed care penetration in the
      site, and the level of Medicaid managed care penetration in the state.
      Uninsurance rate is defined as the percentage of people uninsured in the site.
      Measures of access include the percentage with a usual source of care, percentage
      with any ambulatory care use, and percentage of persons who reported unmet
      medical care needs. Estimates are adjusted to control for other confounding
      factors, including both individual and market-level characteristics. DATA
      COLLECTION: A survey, primarily telephoned, of households concentrated in 60
      sites, defined as metropolitan statistical areas and nonmetropolitan areas.
      PRINCIPAL FINDINGS: Access to care for low-income uninsured persons is lower in
      states with high Medicaid managed care penetration, compared to uninsured persons
      in states with low Medicaid managed care penetration. Access to care for low
      income uninsured persons is also lower in areas with high uninsurance rates. The
      "access gap" (differences in access between insured and uninsured persons) is
      also larger in areas with high Medicaid managed care penetration and areas with
      high uninsurance rates. CONCLUSIONS: Efforts to achieve cost savings under
      managed care may result in financial pressures that limit cross-subsidization of
      care to the medically indigent, particularly for those providers who are heavily
      dependent on Medicaid revenue. High demand for care (as reflected in high
      uninsurance rates) may further strain limited resources for indigent care,
      further limiting access to care for uninsured persons.

PMID- 10199674
TI  - Changes in access to care, 1977-1996: the role of health insurance.
AB  - OBJECTIVE: To describe changes in Americans' access to care over the last 20
      years focusing on the uninsured, Hispanic American, and young adult populations,
      and to analyze the factors underlying these changes with a particular focus on
      the role of health insurance. DATA SOURCES/STUDY SETTING: Data from the 1977
      National Medical Care Expenditure Survey, the 1987 National Medical Expenditure
      Survey, and the 1996 Medical Expenditure Panel Survey. STUDY DESIGN: Focusing on
      whether each individual has a usual source of health care, we present descriptive
      statistics and algebraic decompositions. DATA COLLECTION/EXTRACTION METHODS: We
      combine data from the household surveys with questions from access to care
      supplements that were administered each time. PRINCIPAL FINDINGS: Hispanic
      Americans and young adults age 18-24 are more likely to lack a usual source of
      care than other Americans; these inequalities increased over the period studied
      and cannot be explained solely by changes in health insurance coverage.
      CONCLUSIONS: Although increasing health insurance coverage will likely improve
      access to care among Hispanics and young adults, our findings suggest that the
      expansion of insurance coverage will not be sufficient to eliminate current
      disparities in access to care.

PMID- 10199675
TI  - A conflict of strategies: Medicaid managed care and Medicaid maximization.
AB  - OBJECTIVE: To examine the influence of state strategies aimed at increasing
      federal Medicaid matching dollars on the design of states' Medicaid managed care
      programs. STUDY DESIGN: Data obtained from the 1996-1997 case studies of 13
      states to examine how states have adapted the design of their Medicaid managed
      care programs in part because of maximization strategies, to accommodate the many
      roles and responsibilities that Medicaid has assumed over the years. PRINCIPAL
      FINDINGS: Our study showed that as states made the shift to managed care, some
      found that the responsibilities undertaken in part through maximization
      strategies proved to be in conflict with their Medicaid managed care initiatives.
      Among other things, the study revealed that most states included provisions that
      preserved the health care safety net, such as adapting the managed care benefit
      package and promoting the participation of safety net providers in managed care
      programs. In addition, most of the study states continued to pay special
      subsidies to safety net providers, including hospitals and clinics. CONCLUSIONS:
      States have made real progress in moving a large number of Medicaid beneficiaries
      into managed care. At the same time, many states have specially crafted their
      managed care programs to accommodate safety net providers and existing funding
      mechanisms. By making these adaptations states, in the long run, may compromise
      the central goals of managed care: controlling costs and improving Medicaid
      beneficiaries' access to and quality of care.

PMID- 10199676
TI  - Shaping the future of Medicare.
AB  - This article suggests that further major changes in Medicare at this time are
      unwarranted. The enactment of the Balanced Budget Act (BBA) has eliminated the
      need for quick action to assure solvency of the Part A Trust Fund, which is
      projected to be in balance for at least ten years. It will take time to implement
      and assess the effects of the BBA. The uncertainties of future trends in the
      health sector and Medicare suggest a go-slow approach. Future reforms to finance
      health care as the baby boom generation retires should be guided by the goals of
      continuing to assure health and economic security to elderly and disabled
      beneficiaries, with particular attention to the financial burdens on lower-income
      beneficiaries and those with serious illnesses or chronic conditions. Employers
      are cutting back on retiree health coverage, and the appropriate contribution of
      employers will need to be addressed. The BBA included major provisions to expand
      Medicare managed care choices. Special attention will need to be given to how
      well these innovations work, their cost impact on Medicare, the extent to which
      beneficiaries are able to make informed choices, and whether risk selection among
      plans and between traditional Medicare and plans can be adequately addressed.
      Most of the savings of BBA came from tighter payment rates to managed care plans
      and fee-for-service providers; it is unclear whether these will lead to rates
      well below the private sector or whether further savings can be achieved by
      extending these changes beyond 2002.

PMID- 10199677
TI  - Perceived financial incentives, HMO market penetration, and physicians' practice
      styles and satisfaction.
AB  - OBJECTIVE: To estimate the effects of physicians' personal financial incentives
      and other measures of involvement with HMOs on three measures of satisfaction and
      practice style: overall practice satisfaction, the extent to which prior
      expectations about professional autonomy and the ability to practice good-quality
      medicine are met, and several specific measures of practice style. DATA SOURCES:
      A telephone survey conducted in 1997 of 1,549 physicians who were located in the
      75 largest Metropolitan Statistical Areas in 1991. Eligible physicians were under
      age 52, had between 8 and 17 years of post-residency practice experience, and
      spent at least 20 hours per week in patient care. The response rate was 74
      percent. STUDY DESIGN: Multivariate binomial and multinomial ordered logistic
      regression models were estimated. Independent variables included physicians' self
      reported financial incentives, measured by the extent to which their overall
      financial arrangements created an incentive to either reduce or increase services
      to patients, the level of HMO penetration in the market, employment setting,
      medical specialty, exposure to managed care while in medical training, and
      selected personal characteristics. PRINCIPAL FINDINGS: About 15 percent of survey
      respondents reported a moderate or strong incentive to reduce services; 70
      percent reported a neutral incentive; and 15 percent reported an incentive to
      increase services. Compared to physicians with a neutral incentive, physicians
      with an incentive to reduce services were from 1.5 to 3.5 times more likely to be
      very dissatisfied with their practices and were 0.2 to 0.5 times as likely to
      report that their expectations regarding professional autonomy and ability to
      practice good-quality medicine were met. They were also 0.2 to 0.6 times as
      likely to report having the freedom to care for patients the way they would like
      along several specific measures of practice style, such as sufficient time with
      patients, ability to hospitalize, ability to order tests and procedures, and
      ability to make referrals. These effects were generally reinforced by practicing
      in an area with a high level of HMO penetration and were offset to some extent by
      having had exposure to HMOs and the practice of cost-effective medicine while in
      medical training. CONCLUSIONS: Although financial incentives to reduce services
      are not widespread, there is a legitimate reason to be concerned about possible
      adverse affects on the quality of care. More research is needed to investigate
      directly whether changes in patients' health are affected by their physicians'
      financial incentives.

PMID- 10199678
TI  - Variations in primary care physician referral rates.
AB  - OBJECTIVE: To examine primary care physician referral rate variations, including
      their extent and their stability over time and across diagnostic categories. DATA
      SOURCES: 1995/1996 claims data for adult patients from a large Independent
      Practitioner Association (IPA) model managed care organization (MCO) in the
      Rochester, NY metropolitan area. The IPA includes over 95 percent of area primary
      care physicians (PCPs), and the MCO includes over 50 percent area residents.
      STUDY DESIGN: Referral rates (patients referred to and seen by specialists one or
      more times/patients seen by PCP/year) were developed for the PCPs (457 general
      practitioners, family physicians, and internists) in the MCO, including observed
      referral rates, expected referral rates based on case-mix adjustment across the
      whole sample, physician-specific case mix-adjusted referral rates (empirical
      Bayes estimates), and diagnostic category-specific case mix-adjusted referral
      rates. PRINCIPAL FINDINGS: Wide variations in observed referral rates (0.01-0.69
      patients referred/patients seen/year) were attenuated relatively little by case
      mix adjustment and persisted in case mix-adjusted empirical Bayes estimates (0.02
      0.65). The year-to-year case mix-adjusted referral rate correlation was .90.
      Correlations of case mix adjusted-referral rates across diagnostic categories
      were moderate (r=.46-.67). CONCLUSIONS: PCP referral rates exhibit wide
      variations that are independent of case mix, remain stable over time, and are
      generalizable across diagnostic categories. Understanding this physician practice
      variation and its relationship to costs and outcomes is critical to evaluating
      the effect of current efforts to reduce PCP referral rates.

PMID- 10199679
TI  - Medicare physician referral patterns.
AB  - OBJECTIVE: To study patterns of referral between primary and specialty care
      providers among Medicare beneficiaries and to identify correlates of the
      probability of referral. DATA SOURCES: The 1992 and 1993 Medicare Current
      Beneficiary Survey (MCBS), including associated claims data. MCBS data are linked
      to the Area Resource File (ARF) and the Physician Identification Master Record
      (PIMR). STUDY DESIGN: This is a retrospective design using cross-sectional
      descriptive and multivariate correlational analysis. Estimates are made for two
      years. Key variables include two alternative definitions of referrals, patient
      socio-demographic and health status, physician characteristics, and county-level
      descriptors. DATA COLLECTION: The MCBS is a panel survey of a stratified random
      sample of Medicare beneficiaries begun in 1991. The data are linked to Medicare
      claims records for survey respondents. The ARF is a health resources data set
      that contains more than 7,000 variables at the county level, including
      information on health facilities, health professions, services resources and
      utilization, and socioeconomic and environmental characteristics. The PIMR is a
      record of all physicians in the United States and describes their professional
      characteristics. PRINCIPAL FINDINGS: The overall rate of physician referrals in
      the MCBS, approximately 10 percent, is higher than that found in prior research,
      as is the level of self-referral to specialists at about 70 percent. Depending on
      the dependent variable definition, between 60 and 85 percent of all Medicare
      beneficiaries had at least one referral, and the average number of referrals per
      person per year was greater than two. Referrals show a multi-directional pattern
      rather than a simple pattern of primary to specialty care, with referrals between
      primary care physicians, referrals between specialists, and referrals from
      specialty to primary care being not uncommon. Strong predictors of referral
      include patient health and patient insurance coverage and income. Physician
      factors do not contribute much to explaining referrals. CONCLUSIONS: Medicare
      referral patterns are similar to those found in other studies. Patient factors
      appear to be a more important factor in explaining referrals than was estimated
      from prior research. Additional research is needed to explain the more complex
      dynamics of referral patterns.

PMID- 10199680
TI  - Conditional Length of Stay.
AB  - OBJECTIVE: To develop and test a new outcome measure, Conditional Length of Stay
      (CLOS), to assess hospital performance when deaths are rare and complication data
      are not available. DATA SOURCES: The 1991 and 1992 MedisGroups National
      Comparative Data Base. STUDY DESIGN: We use engineering reliability theory
      traditionally applied to estimate mechanical failure rates to construct a CLOS
      measure. Specifically, we use the Hollander-Proschan statistic to test if LOS
      distributions display an "extended" pattern of decreasing hazards after a
      transition point, suggesting that "the longer a patient has stayed in the
      hospital, the longer a patient will likely stay in the hospital" versus an
      alternative possibility that "the longer a patient has stayed in the hospital,
      the faster a patient will likely be discharged from the hospital." DATA
      COLLECTION/EXTRACTION METHODS: Abstracted records from 7,777 pediatric pneumonia
      cases and 3,413 pediatric appendectomy cases were available for analysis.
      PRINCIPAL FINDINGS: For both conditions, the Hollander-Proschan statistic
      strongly displays an "extended" pattern of LOS by day 3 (p<.0001) associated with
      declining rates of discharge. This extended pattern coincides with increasing
      patient complication rates. Worse admission severity and chronic disease
      contribute to lower rates of discharge after day 3. CONCLUSIONS: Patient stays
      tend to become prolonged after complications. By studying CLOS, one can determine
      when the rate of hospital discharge begins to diminish--without the need to
      directly observe complications. Policymakers looking for an objective outcome
      measure may find that CLOS aids in the analysis of a hospital's management of
      complicated patients without requiring complication data, thereby facilitating
      analyses concerning the management of patients whose care has become complicated.

PMID- 10199682
TI  - Barriers between guidelines and improved patient care: an analysis of AHCPR's
      Unstable Angina Clinical Practice Guideline. Agency for Health Care Policy and
      Research.
AB  - OBJECTIVES: To describe common barriers that limit the effect of guidelines on
      patient care, with emphasis on recommendations for triage in the Agency for
      Health Care Policy and Research (AHCPR) Unstable Angina Clinical Practice
      Guideline. DATA SOURCES: Previously reported results from a prospective clinical
      study of 10,785 patients presenting to the emergency department (ED) with
      symptoms suggestive of acute cardiac ischemia. STUDY DESIGN: Design is an
      analysis of the AHCPR guideline with regard to recognized barriers in guideline
      implementation. Presentation of hypothetical scenarios to ED physicians was used
      to determine interrater reliability in applying the guideline to assess risk and
      to make triage decisions. PRINCIPAL FINDINGS: The AHCPR guideline's triage
      recommendations demonstrate (1) poor interobserver reliability in interpretation
      by ED physicians; (2) limited applicability of recommendations for outpatient
      management (applies to 6 percent of patients presenting to the ED with unstable
      angina); (3) incomplete specifications of exceptions that may require deviation
      from guideline recommendations; (4) unexpected effects on medical care by
      significantly increasing the demand for limited intensive care beds; and (5)
      unknown effects on patient outcomes. In addition, analysis of the guideline
      highlights the need to address organizational barriers, such as administrative
      policies that conflict with guideline recommendations and the need to adapt the
      guideline to conform to local systems of care. CONCLUSIONS: Careful analysis of
      guideline attributes, projected effect on medical care, and organizational
      factors reveal several barriers to successful guideline implementation that
      should be addressed in the design of future guideline-based interventions.

PMID- 10199681
TI  - How much better can we predict dialysis patient survival using clinical data?
AB  - OBJECTIVE: To use three approaches to compare dialysis survival prediction based
      on variables included in the Standardized Mortality Ratio (SMR) with prediction
      based on a clinically enriched set of variables. DATA SOURCE: The United States
      Renal Data System Case Mix Severity data set containing demographic, clinical,
      functional, nutritional, and treatment details about a random sample of 4,797
      adult dialysis patients from 291 treatment units, incident to dialysis in 1986
      and 1987. STUDY DESIGN: This observational study uses baseline patient
      characteristics in two proportional hazards survival models: the BASE model
      incorporates age, race, sex, and cause of end-stage renal disease (ESRD); the
      FULL model includes these and additional clinical information. We compare each
      model's performance using (1) the c-index, (2) observed median survival in strata
      of predicted risk, and (3) predicted survival for patients with different
      characteristics. PRINCIPAL FINDINGS: The FULL model's c-index (0.709, 0.708
      0.711) is significantly higher than that of the BASE model (0.675, 0.675-0.676),
      indicating better discrimination. Second, the sickest patients identified by the
      FULL model were in fact sicker than those identified as sickest by the BASE
      model, with observed median survival of 451 days versus 524. Third, survival
      predictions for sickest patients using the FULL model are one-third shorter than
      those based on the BASE model. CONCLUSIONS: The model with more detailed clinical
      information predicted survival better than the BASE model. Clinical
      characteristics enable more accurate predictions, particularly for the sickest
      patients. Thus, clinical characteristics should be considered when making quality
      assessments for dialysis patients.

PMID- 10199683
TI  - Developing quality measures for adolescent care: validity of adolescents' self
      reported receipt of preventive services.
AB  - OBJECTIVE: To demonstrate the feasibility of directly surveying adolescents about
      the content of preventive health services they have received and to assess the
      validity of adolescent self-reported recall. DATA SOURCES/SETTING: Audiotaped
      encounters, telephone interviews, and chart reviews with 14-21 year olds being
      seen for preventive care visits at 15 pediatric and family medicine private
      practices, teaching hospital clinics, and health centers. DESIGN: 537 adolescents
      presenting for well visits were approached, 400 (75 percent) consented, 374 (94
      percent) were audiotaped, and 354 (89 percent) completed telephone interviews
      either two to four weeks or five to seven months after their visits. Audiotapes
      were coded for screening and counseling across 34 preventive service content
      areas. Intraobserver reliability (Cohen's kappa) ranged from 0.45 for talking
      about peers to 0.94 for discussing tobacco. The sensitivity and specificity of
      the adolescent self-reports were assessed using the audiotape coding as the gold
      standard. RESULTS: Almost all adolescents surveyed (94 percent) remembered having
      had a preventive care visit, 93 percent identified the site of care, and most (84
      percent) identified the clinician they had seen. There was wide variation in the
      prevalence of screening, based on the tape coding. Adolescent self-report was
      moderately or highly sensitive and specific at two weeks and six months for 24 of
      34 screening and counseling items, including having discussed: weight, diet, body
      image, exercise, seatbelts, bike helmet use, cigarettes/smoking, smokeless
      tobacco, alcohol, drugs, steroids, sex, sexual orientation, birth control,
      condoms, HIV, STDs, school, family, future plans, emotions, suicidality, and
      abuse. Self-report was least accurate for blood pressure/cholesterol screening,
      immunizations, or for having discussed fighting, violence, weapon carrying,
      sleep, dental care, friends, or over-the-counter drug use. CONCLUSION:
      Adolescents' self-report of the care they have received is a valid method of
      determining the content of preventive health service delivery. Although recall of
      screening and counseling is more accurate within two to four weeks after
      preventive care visits, adolescents can report accurately on the care they had
      received five to seven months after the preventive health care visits occurred.

PMID- 10199684
TI  - Impact of a DRG-based hospital financing system on quality and outcomes of care
      in Italy.
AB  - OBJECTIVE: To examine potential changes in quality of care associated with a
      recent financing system implementation in Italy: in 1995, hospital financing
      reform implemented in Italy included the introduction of a DRG-based hospital
      financing system with the goals of controlling the growth of hospital costs and
      making hospitals more accountable for their productivity. DATA SOURCES: Hospital
      discharge abstract data from 1993 through 1996 for all hospitals (N=32) in the
      Friuli-Venezia-Giulia region of Italy. Regional population data were used to
      calculate rates. STUDY DESIGN: Changes between 1993 and 1996 in hospital
      admissions, length of stay, mortality rates, severity of illness, and readmission
      rates were studied for nine common medical and surgical conditions: appendicitis,
      diabetes mellitus, colorectal cancer, cholecystitis, bronchitis/chronic
      obstructive pulmonary disease (COPD), bacterial pneumonia, coronary artery
      disease, cerebrovascular disease, and hip fracture. PRINCIPAL FINDINGS: The total
      number of ordinary hospital admissions decreased from 244,581 to 204,054 between
      1993 and 1996, a population-based decrease of 17.3 percent (p<.001). The mean
      length of stay decreased from 9.1 days to 8.8 days, resulting in a 21.1 percent
      decrease in hospital bed days (p<.001). Day hospital use increased sevenfold from
      16,871 encounters in 1993 to 108,517 encounters in 1996. The largest decrease in
      hospital admissions among study conditions was a 41 percent decrease for diabetes
      (from 2.25 per 1,000 in 1993 to 1.31 in 1996, p<.001). For eight of the nine
      conditions, severity of illness increased. Differences between severity-adjusted
      expected and observed in-hospital mortality rates were small. CONCLUSIONS:
      Observed trends showed a decrease in ordinary hospital admissions, an increase in
      day hospital admissions, and a greater severity of illness among hospitalized
      patients. There was little or no change in mortality and readmission rates.
      Administrative data can be used to track changes in patterns of care and to
      identify potential quality problems deserving further review.

PMID- 10199685
TI  - Medical records and privacy: empirical effects of legislation.
AB  - OBJECTIVE: To determine the effects of state legislation requiring patient
      informed consent prior to medical record abstraction by external researchers for
      a specific study. DATA SOURCES/STUDY SETTING: Informed consent responses obtained
      from November 1997 through April 1998 from members of a Minnesota-based IPA model
      health plan. STUDY DESIGN: Descriptive case study of consent to gain access to
      medical records for a pharmaco-epidemiologic study of seizures associated with
      use of a pain medication that was conducted as part of the FDA's post-marketing
      safety surveillance program to evaluate adverse events associated with approved
      drugs. DATA COLLECTION: The informed consent process approved by an institutional
      review board consisted of three phases: (1) a letter from the health plan's
      medical director requesting participation, (2) a second mailing to
      nonrespondents, and (3) a follow-up telephone call to nonrespondents. PRINCIPAL
      FINDINGS: Of 140 Minnesota health plan members asked to participate in the
      medical records study, 52 percent (73) responded and 19 percent (26) returned a
      signed consent form authorizing access to their records for the study. For 132
      study subjects enrolled in five other health plans in states where study-specific
      consent was not required, health care providers granted access to patient medical
      records for 93 percent (123) of the members. CONCLUSION: Legislation requiring
      patient informed consent to gain access to medical records for a specific
      research study was associated with low participation and increased time to
      complete that observational study. Efforts to protect patient privacy may come
      into conflict with the ability to produce timely and valid research to safeguard
      and improve public health.

PMID- 10199686
TI  - Health services research in workers' compensation medical care: policy issues and
      research opportunities.
AB  - OBJECTIVE: To describe some of the unique aspects of medical care offered under
      workers' compensation insurance systems and discuss the major policy
      considerations relevant to health services researchers undertaking investigations
      in this area. BACKGROUND AND FINDINGS: State-based workers' compensation (WC)
      insurance systems requiring employers to pay for medical care and wage
      replacement for workplace injuries and illnesses were first developed between
      1910 and 1920 in the United States. Employers are generally required to purchase
      state-regulated workers' compensation insurance that includes first-dollar
      payment for all medical and rehabilitative services and payment of lost wages to
      workers with work-related illness or injury. Injured workers have variable but
      usually limited latitude in choosing their health care provider. Employers and
      workers' compensation insurers have incentives for controlling both the cost of
      medical care and lost wages. CONCLUSION: The major policy issues in WC medical
      care--the effect of patient choice of provider and delivery system structure, the
      ensuring of high-quality care, the effect of integrating benefits, and
      investigation of the interrelationships between work, health, and productivity-
      can be informed by current studies in health services research and by targeted
      future studies of workers' compensation populations. These studies must consider
      the extent of patient choice of physician, the regulatory environment, the unique
      role of the workplace as a risk and modifying factor, and the complex interaction
      between health and disability insurance benefits.

PMID- 10199687
TI  - Factors affecting bargaining outcomes between pharmacies and insurers.
AB  - OBJECTIVE: To model the bargaining power of pharmacies and insurers in price
      negotiations and test whether it varies with characteristics of the pharmacy,
      insurer, and pharmacy market. DATA SOURCES/STUDY SETTING: Data from four sources.
      Pharmacy/insurer transactions were taken from Medstat's universe of 6.8 million
      pharmacy claims in their 1994 Marketscan database. Sources Informatics, Inc.
      supplied a three-digit zip code-level summary database containing pharmacy
      payments and self-reported costs for retail (cash-paying) customers for the top
      200 pharmaceutical products by prescription size in 1994. The National Council of
      Prescription Drug Programs supplied their 1994 pharmacy database. Zip code-level
      socioeconomic and commercial information was taken from Bureau of the Census'
      1990 Summary Tape File 3B and 1994 Zip Code Business Patterns database. STUDY
      DESIGN: The provider/insurer bargaining model first employed in Brooks, Dor, and
      Wong (1997, 1998) was adapted to the circumstances surrounding pharmacy and
      insurer bargaining. DATA COLLECTION/EXTRACTION METHODS: The units of observation
      in this study were single Medstat claims for each unique insurer/pharmacy
      combination in the database for selected pharmaceutical products. The four
      products selected varied in the conditions they treat, whether they are used to
      treat chronic or acute conditions, and by their sales volume. Used in the
      analysis were 9,758 Zantac, 2,681 Humulin, 3,437 Mevacor, and 1,860 Dilantin
      observations. PRINCIPAL FINDINGS: We find statistically significant variation in
      pharmacy bargaining power. Pharmacy bargaining power varies significantly across
      markets, insurers, and pharmacy types. With respect to market structure, pharmacy
      bargaining power is negatively related to pharmacies per capita and pharmacies
      per employer and positively related to pharmacy concentration at higher
      concentration levels. In addition, the higher the percentage of independent
      pharmacies in an area, the lower the pharmacy bargaining power. With respect to
      socioeconomic conditions, pharmacy bargaining power is higher in areas with lower
      per capita income and higher rates of public assistance. CONCLUSIONS: The
      bargaining power of pharmacies in contract negotiations with insurers varies
      considerably with exogenous factors. Local area pharmacy ownership concentration
      enhances pharmacy bargaining. As a result, anti-trust law prohibiting the
      collective bargaining of independent pharmacies with insurers leaves independents
      at a disadvantage with respect to chains.

PMID- 10199688
TI  - Mechanical contribution of endocardium during finite extension and torsion
      experiments on papillary muscles.
AB  - Finite extension and torsion tests on cardiac papillary muscles are presently the
      best way to directly measure the response to shear along myocardial fibers.
      Quantifying this response is necessary for determining the complete three
      dimensional constitutive behavior of myocardium as a transversely isotropic
      material. Analysis of such tests is complicated, however, since papillary muscles
      are materially inhomogeneous, consisting of a myocardial core surrounded by an
      endocardial sheath that is rich in collagen. In this article, we show that the
      papillary muscle response to extension and torsion additively decouples into the
      response of the bare myocardial core plus the response of an endocardial sheath
      filled with fluid (assuming the muscle is a radially inhomogeneous and
      incompressible continuum with cylindrical symmetry). This result allows the
      endocardial response to be subtracted from the intact papillary muscle response
      to obtain the response of the bare myocardial core. An initial estimate suggests
      that the endocardial sheath affects the axial moment significantly (50% of torque
      for all twists at low stretch) but affects the axial force only slightly (<10% at
      moderate twists).

PMID- 10199689
TI  - Changes in passive but not active mechanical properties predict recovery of
      function of stunned myocardium.
AB  - The time course of alterations in active and passive mechanical properties of
      stunned myocardium during ischemia and throughout reperfusion has not been
      thoroughly quantified. This investigation tested the hypothesis that the amount
      of injury as well as the rate and extent of recovery of contractile function in
      postischemic, reperfused myocardium are directly correlated to changes in
      regional active and passive elastance and viscosity. A modified viscoelastic
      Voigt model was employed to quantify myocardial mechanical properties. Left
      ventricular pressure and segment length (in both ischemic and normal regions)
      were fit to the model consisting of an active elastic spring in parallel with a
      viscous damper and a passive elastic spring. The mechanical properties of
      myocardium from dogs which recovered (> or = 50%) baseline regional contractile
      function as determined by percent segment shortening (n=7) were compared to those
      from dogs that did not recover function (n=7). Both groups displayed decreased
      active elastance in the ischemic region during coronary artery occlusion, and
      this decrease was maintained in the nonrecovery group. Increases in viscosity of
      ischemic myocardium were observed in both groups during coronary occlusion but
      returned to control only in the recovery group. The nonrecovery group
      demonstrated increased passive elastance in the ischemic region during coronary
      occlusion and throughout the reperfusion period whereas the recovery group
      remained unchanged. We conclude that functional recovery of stunned myocardium is
      directly related to alterations in mechanical properties caused by ischemia and
      that changes in passive elastance during occlusion may predict the ability of
      ischemic myocardium to recover contractile function.

PMID- 10199690
TI  - Conductance method for the measurement of cross-sectional areas of the aorta.
AB  - A modified conductance method to determine the cross-sectional areas (CSAs) of
      arteries in piglets was evaluated in vivo. The method utilized a conductance
      catheter having four electrodes. Between the outer electrodes an alternating
      current was applied and between the inner electrodes the induced voltage
      difference was measured and converted into a conductance. CSA was determined from
      measured conductance minus parallel conductance, which is the conductance of the
      tissues surrounding the vessel times the length between the measuring electrodes
      of the conductance catheter divided by the conductivity of blood. The parallel
      conductance was determined by injecting hypertonic saline to change blood
      conductivity. The conductivity of blood was calculated from temperature and
      hematocrit and corrected for maximal deformation and changes in orientation of
      the erythrocytes under shear stress conditions. The equations to calculate the
      conductivity of blood were obtained from in vitro experiments. In vivo average
      aortic CSAs. determined with the conductance method CSA(G) in five piglets, were
      compared to those determined with the intravascular ultrasound method CSA(IVUS).
      The regression equation between both values was CSA(G)=-0.09+1.00 x CSA(IVUS),
      r=0.97, n=53. The mean difference between the values was -0.29%+/-5.57% (2
      standard deviations). We conclude that the modified conductance method is a
      reliable technique to estimate the average cross-sectional areas of the aorta in
      piglets.

PMID- 10199691
TI  - Finite element model determination of correction factors used for measurement of
      aortic diameter via conductance.
AB  - Traditional methods for estimating the slope alpha and offset volume Vp for
      determining real-time chamber volume by the conductance catheter technique are
      not suited to measurements made in the aorta due to the relatively low
      resistivity of the aortic wall. We developed three distinct three-dimensional
      finite element models of the conductance catheter and surrounding tissues in
      order to predict alpha and Vp and to examine the nature of the electric field
      near the aortic wall. A heterogeneous isotropic model of the catheter, aorta and
      surrounding tissues accurately predicted the values of alpha and Vp. A
      homogeneous anisotropic model was developed to examine the effects of anisotropy
      of blood and the layers of the aortic wall on measured values of resistance,
      alpha and Vp. This model demonstrated that anisotropy of blood and aortic wall
      tissue can increase the values of both alpha and Vp. Finally, a three-dimensional
      homogeneous isotropic rectangular model allowed examination of the effects of
      catheter position. This model showed small effects of catheter position on
      measured resistance (9.7% increase) and larger effects on alpha (21.2% decrease)
      and Vp (41.9% increase). We conclude the following: the FEA models may lead to
      accurate estimate values of alpha and Vp in vivo. The unique anisotropic
      conductive properties of the layers of the aortic wall contribute to the high
      observed values of alpha and Vp in the aorta. Finally, catheter position has a
      proportionately greater effect on alpha and Vp than on measured resistance. The
      results of this study should assist in the determination of aortic mechanical
      properties using conductance catheter measurements of vessel dimension.

PMID- 10199692
TI  - Computationally efficient model for simulating electrical activity in cardiac
      tissue with fiber rotation.
AB  - Transmural rotation of cardiac fibers may have a large influence on the
      initiation, stabilization, and termination of several life threatening cardiac
      arrhythmias. However, three-dimensional modeling of reentry in cardiac tissue is
      computationally demanding, as a tissue on the order of centimeters in size must
      be used to sustain reentry and several seconds must be simulated. Numerical
      accuracy requires time steps on the order of microseconds and spatial
      discretization on the order of microns. Consequently, the resultant numerical
      systems are extremely large. In this article, a computationally efficient model
      of a three-dimensional block of cardiac tissue with fiber rotation is presented.
      Computational speedup is achieved by using a discrete cable model which allowed
      for system order reduction, and also by using a scheme for tracking the
      activation wave front which identified regions requiring integration with a small
      time step. Simulating 1.2 s of activity of the approximately 2 x 10(6) cells
      constituting a block measuring 2.0 x 4.0 x 0.29 cm was performed in 26 h. Effects
      of model parameters on performance are discussed. The effect of fiber rotation on
      the spread of electrical activity after point source stimulation and a cross
      shock protocol is clearly demonstrated.

PMID- 10199693
TI  - Bispectral energies within electrocardiograms during ventricular fibrillation are
      correlated with defibrillation shock outcome.
AB  - We investigated whether the degree of phase coupling among orthogonal
      electrocardiograms during ventricular fibrillation (VF) was correlated with
      defibrillation shock outcome. We used cross bispectrum to estimate the degree of
      phase coupling. In dogs, VF was electrically induced and terminated with a
      defibrillation shock with a 50% probability of success. The defibrillation shock
      was delivered between the right ventricular apex and a subcutaneous patch
      electrode. Bispectra were integrated within 8.7-11.7, 8.7-11.7 Hz bandwidths and
      compared between those trials for which the defibrillation shocks were successful
      (206 trials, 49%) and unsuccessful (221 trials, 51%) in terminating VF. Results
      showed that between 200 and 1000 ms before defibrillation shock, unsuccessful
      trials had greater bispectral energy than successful trials (p<0.05). Although
      correlations between degree of phase coupling and shock outcome do not indicate
      causal relationship or predictability, they provide further evidence of the
      organization during fibrillation. We discuss the nonstationary wavelet
      hypothesis, previously proposed in the literature by other investigators, as one
      of the possible mechanisms to explain the correlation between bispectral energy
      and shock outcome.

PMID- 10199694
TI  - Practical real-time computing system for biomedical experiment interface.
AB  - Many biomedical experiments require a precisely timed real-time (RT) computer
      interface. Because commonly used desktop operating systems are inherently non
      real-time, real-time laboratory computer systems are often based on outdated DOS
      software or expensive proprietary real-time operating systems. Here we discuss a
      real-time computing system, based on the free RT-LINUX operating system, which we
      have developed for adaptive pacing control in a clinical cardiac
      electrophysiology laboratory. This powerful, flexible, and inexpensive system
      demonstrates that RT-LINUX is well suited for real-time biomedical experiment
      interface.

PMID- 10199695
TI  - New method to obtain ultrasonic angle independent Doppler color images using a
      sector transducer.
AB  - A new method based on the multiple beam procedure to obtain ultrasonic angle
      independent Doppler color (AIDC) images using Doppler color imaging with a sector
      transducer has been developed. The transducer was sequentially placed at three
      locations with different direction orientations to acquire velocity information
      for the same flow field. Equations have been derived and used to obtain the
      velocity amplitude and flow direction angle for each point in the flow field from
      the acquired velocity data and the known positions of the transducer. AIDC images
      then can be reconstructed. To evaluate the feasibility of this method, AIDC
      images using a sector transducer have been reconstructed for steady flow fields
      in a latex tube model and for blood flow in the abdominal aorta of normal human
      subjects. The quantitative results obtained using this method were in reasonably
      good agreement with those obtained from existing reference methods.

PMID- 10199696
TI  - Quantitative assessment of steady and pulsatile flow fields in a parallel plate
      flow chamber.
AB  - Steady and pulsatile flows were imaged and quantified in a parallel plate flow
      chamber that was designed to allow constant variation of the volumetric flow rate
      and to minimize pressure gradients across the width of the flow field. Results
      indicated that both the steady and pulsatile flow fields were uniform across the
      width of the flow chamber as shown by linear regression analysis. Further, the
      dynamic effects of the fluid pulse were transmitted almost instantaneously across
      the length of the flow field. These findings verify that parallel plate devices
      designed in this manner are suitable for delivering uniform steady and pulsatile
      shear stress to adherent cell populations in vitro.

PMID- 10199697
TI  - A priori identifiability of distributed models of blood-tissue exchange.
AB  - A priori identifiability deals with the uniqueness of the solution for the
      unknown parameters of a dynamic model from a given input-output experiment, and
      is a prerequisite for well posedness of parameter estimation from the data.
      Identifiability has been extensively investigated for lumped parameter, linear,
      and nonlinear dynamic models, in particular, compartmental models of biological
      systems. Much less attention has been devoted to distributed parameter model, in
      particular, those describing blood-tissue exchange, which are normally used to
      interpret regional multiple tracer dilution experiments. In this paper, we study
      a priori identifiability of distributed parameter models of transcapillary
      exchange, focusing first on a single capillary (one-region) model, then moving on
      to a single capillary-interstitial fluid (two-region) model, and finally to an
      organ model also describing flow heterogeneity.

PMID- 10199698
TI  - Single cell model for simultaneous drug delivery and efflux.
AB  - Multidrug resistance (MDR) of some cancer cells is a major challenge for
      chemotherapy of systemic cancers to overcome. To experimentally uncover the
      cellular mechanisms leading to MDR, it is necessary to quantitatively assess both
      drug influx into, and efflux from, the cells exposed to drug treatment. By using
      a novel molecular microdelivery system to enforce continuous and adjustable drug
      influx into single cells by controlled diffusion through a gel plug in a
      micropipet tip, drug resistance studies can now be performed on the single cell
      level. Our dynamic model of this scheme incorporates drug delivery, diffusive
      mixing, and accumulation inside the cytoplasm, and efflux by both passive and
      active membrane transport. Model simulations using available experimental
      information on these processes can assist in the design of MDR related
      experiments on single cancer cells which are expected to lead to a quantitative
      evaluation of mechanisms. Simulations indicate that drug resistance of a cancer
      cell can be quantified better by its dynamic response than by steady-state
      analysis.

PMID- 10199699
TI  - Kinetic model for integrin-mediated adhesion release during cell migration.
AB  - Under many circumstances, cell migration speed is limited by the rate of cell
      substratum detachment at the cell rear. We have constructed a mathematical model
      to integrate how the biophysical and biochemical interactions between integrins,
      the cytoskeleton, and the matrix affect rear retraction and linkage dissociation
      mechanisms. Our model also examines how applied forces and integrin clustering
      affect retraction kinetics. The model predicts two distinct detachment
      phenotypes. In the first, detachment is extremely rapid, dominated by integrin
      extracellular-matrix dissociation, and it occurs at high forces or low
      adhesiveness. In the second, detachment is much slower, dominated by integrin
      cytoskeleton dissociation, and it occurs at low forces or high adhesiveness. The
      amount of integrin extracted from the rear of the cell is an assay for the
      detachment phenotype. During rapid detachment cells leave little integrin on the
      substratum whereas during slow detachment a large fraction of integrin rips from
      the membrane. This model delineates parameters which can be exploited to regulate
      cell speed in each detachment regime. The model also offers an explanation as to
      why some cell types, such as leukocytes or keratocytes, are able to detach easily
      and move very quickly while other cell types, such as fibroblasts, tend to
      migrate more slowly and release many more integrins during detachment.

PMID- 10199700
TI  - Effect of cell-cell interactions on the observable strength of adhesion of sheets
      of cells.
AB  - Previous research in cellular adhesion has focused primarily on studying isolated
      cells under conditions where cells do not interact with each other. However, in
      vivo cells form sheets where both cell-substratum and cell-cell interactions
      contribute to the overall adhesive behavior. Our understanding of how cell-cell
      and cell-substratum interactions affect the overall process of cell adhesion in
      these situations is limited. To address this problem, we developed a systematic
      approach to evaluate how cell-cell and cell-substratum interactions affect the
      critical shear stress for detachment for semi-confluent and confluent sheets of
      cells. Our studies were based on subjecting cultures of adherent cells to a
      defined hydrodynamic flow in a radial-flow chamber with a gap height of 140
      microm. Using phase-contrast microscope imaging and analysis we measured shear
      dependent patterns of detachment as a function of the extent of cell confluency.
      Our results show that the critical shear stress for detachment is maximum at
      intermediate extents of confluency of 10%-40%. These results have important
      implications for sodding vascular grafts and tissue engineering.

PMID- 10199701
TI  - Estimation of tendon moment arms from three-dimensional magnetic resonance
      images.
AB  - New three-dimensional (3D) magnetic resonance imaging (MRI) methods for measuring
      the tendon moment arm were created and were evaluated on the tendon moment arm of
      the flexor digitorum profundus at the third metacarpophalangeal joint. Using an
      open magnet MRI system and a hand holder, a series of static images were acquired
      at four joint angles and analyzed using specially created computer programs.
      Three methods were evaluated: (1) a 3D tendon excursion method that extended the
      method of Landsmeer; (2) a 3D geometric method whereby the moment arm was the
      perpendicular distance between the joint axis of rotation and the tendon path,
      and (3) a two-dimensional (2D) geometric method whereby single image slices were
      analyzed. Repeating the imaging and measurement processes, the 3D tendon
      excursion method was more reproducible (6% variation) than the 3D geometric
      method (12%), and both were much more reproducible than the 2D geometric method
      (27%). By having three operators analyze a single set of image data, we found
      that the precision of the 3D tendon excursion method was much less affected by
      segmentation error than the 3D geometric method. With the 3D imaging methods,
      tendon bowstringing and a displacement of the joint center of rotation toward the
      dorsal side of the hand were evident, leading to as much as a 60% increase in
      moment arm with joint flexion. Because of the dependence on flexion and variation
      between subjects, we recommend patient-specific measurements for target
      applications in functional neuromuscular stimulation interventions and tendon
      transfer surgery.

PMID- 10199703
TI  - Variational approaches toward nonlinear time-series analysis.
AB  - Linear autoregressive models (AR) have broad applications toward spectral
      analyses and digital filtering of signals, as well as identification, prediction,
      and control of dynamical systems. However, the symmetric Gaussian properties of
      linear AR presume independence between the first and second order moments of
      system outputs. Using nonlinear AR to quantify interactions between the mean and
      autocovariance of a signal, analysts can discriminate asymmetric frequency
      components, estimate the relative contribution of system nonlinearities toward
      mean output, evaluate relative structural stability of a system, and predict
      critical regions where bifurcations in its dynamics might occur. Quadratic
      analyses are performed on simulated outputs from a nonlinear model and various
      experimental time series (Canadian lynx population, respiratory volume dynamics
      in rat, Cheyne-Stokes respiration in patients with congestive heart failure,
      intracranial pressures in patient with cerebral hematoma). These case studies
      demonstrate the utility of the techniques for evaluating the qualitative
      behaviors of dynamical systems in the presence of slowly varying inputs.

PMID- 10199704
TI  - Response on drug policy.

PMID- 10199702
TI  - Hemodynamic effect of cerebral vasospasm in humans: a modeling study.
AB  - A mathematical model of cerebral hemodynamics during vasospasm is presented. The
      model divides arterial hemodynamics into two cerebral territories: with and
      without spasm. It also includes collateral circulation between the two
      territories, cerebral venous hemodynamics, cerebrospinal fluid circulation,
      intracranial pressure (ICP) and the craniospinal storage capacity. Moreover, the
      pial artery circulation in both territories is affected by cerebral blood flow
      (CBF) autoregulation mechanisms. In this work, a numerical value to model
      parameters was given assuming that vasospasm affects only a single middle
      cerebral artery (MCA). In a first stage, the model is used to simulate some
      clinical results reported in the literature, concerning the patterns of MCA
      velocity, CBF and pressure losses during vasospasm. The agreement with clinical
      data turns out fairly good. In a second stage, a sensitivity analysis on some
      model parameters is performed (severity of caliber reduction, longitudinal
      extension of the spasm, autoregulation gain, ICP, resistance of the collateral
      circulation, and mean systemic arterial pressure) to clarify their influence on
      hemodynamics in the spastic territory. The results suggest that the clinical
      impact of vasospasm depends on several concomitant factors, which should be
      simultaneously taken into account to reach a proper diagnosis. In particular,
      while a negative correlation between MCA velocity and cross sectional area can be
      found until CBF is well preserved, a positive correlation may occur when CBF
      starts to decrease significantly. This might induce false-negative results if
      vasospasm is assessed merely through velocity measurements performed by the
      transcranial Doppler technique.

PMID- 10199706
TI  - CDC targets arthritis, a leading cause of disability.

PMID- 10199705
TI  - WHO guidelines seek to lower risk of TB transmission during air travel.

PMID- 10199707
TI  - Center to review evidence of chemical threats to human reproduction.

PMID- 10199708
TI  - NHLBI Website: asthma management.

PMID- 10199709
TI  - Limit children's work hours, report says.

PMID- 10199710
TI  - Cities need new drugs, diagnostic tests, and software to prepare for chemical,
      biological attacks.

PMID- 10199711
TI  - AHCPR offers resources for consumers, providers, and health agencies. Agency for
      Health Care Policy and Research.

PMID- 10199713
TI  - How organized medical care can advance public health.

PMID- 10199712
TI  - Nonprofit to for-profit conversions by hospitals, health insurers, and health
      plans.
AB  - Conversion of hospitals, health insurers, and health plans from nonprofit to for
      profit ownership has become a focus of national debate. The author examines why
      nonprofit ownership has been dominant in the US health system and assesses the
      strength of the argument that nonprofits provide community benefits that would be
      threatened by for-profit conversion. The author concludes that many of the
      specific community benefits offered by nonprofits, such as care for the poor,
      could be maintained or replaced by adequate funding of public programs and that
      quality and fairness in treatment can be better assured through clear standards
      of care and adequate monitoring systems. As health care becomes increasingly
      commercialized, the most difficult parts of nonprofits' historic mission to
      preserve are the community orientation, leadership role, and innovation that
      nonprofit hospitals and health plans have provided out of their commitment to a
      community beyond those to whom they sell services.

PMID- 10199714
TI  - Children at work.

PMID- 10199715
TI  - Preventing emerging infectious diseases as we enter the 21st century: CDC's
      strategy.

PMID- 10199716
TI  - Effect of insurance coverage on the relationship between asthma hospitalizations
      and exposure to air pollution.
AB  - OBJECTIVE: Based on the assumption that people without health insurance have
      limited access to the primary care services needed to prevent unnecessary
      hospitalizations for asthma, the authors hypothesized that insurance is a factor
      in the strength of the association between hospital admissions for asthma and
      exposure to air pollution. They tested this hypothesis with 1991-1994 data from
      central Los Angeles. METHODS: The authors analyzed the effect of insurance status
      on the association between asthma-related hospital admissions and exposure to
      atmospheric particulates (PM10) and ozone (O3) using hospital discharge and air
      quality data for 1991-1994 for central Los Angeles. They used regression
      techniques with weighted moving averages (simulating distributed lag structures)
      to measure the effects of exposure on overall hospital admissions, admissions of
      uninsured patients, admissions for which MediCal (California Medicaid) was the
      primary payer, and admissions for which the primary payer was another government
      or private health insurance program. RESULTS: No associations were found between
      asthma admissions and O3 exposure. An estimated increase from 1991 to 1994 of 50
      micrograms per cubic meter in PM10 concentrations averaged over eight days was
      associated with an increase of 21.0% in the number of asthma admissions. An even
      stronger increase--27.4%--was noted among MediCal asthma admissions. CONCLUSIONS:
      The authors conclude that low family income, as indicated by MediCal coverage, is
      a better predictor of asthma exacerbations associated with air pollution than
      lack of insurance and, by implication, a better predictor of insufficient access
      to primary care.

PMID- 10199717
TI  - Counting the uninsured using state-level hospitalization data.
AB  - OBJECTIVE: To assess the appropriateness of using state-level data on uninsured
      hospitalizations to estimate the uninsured population. METHODS: The authors used
      1992-1996 data on hospitalizations of newborns and of appendectomy and heart
      attack patients in Florida to estimate the number of people in the state without
      health insurance coverage. These conditions were selected because they usually
      require hospitalization and they are common across demographic categories.
      RESULTS: Adjusted for the gender and ethnic composition of the population, the
      percentages of uninsured hospitalizations for appendectomies and heart attacks
      produced estimates of the state's uninsured population 1.6 percentage points
      lower than those reported for 1996 in the US Census March Current Population
      Survey. CONCLUSION: Data reported by hospitals to state agencies can be used to
      monitor trends in health insurance coverage and provides an alternative data
      source for a state-level analysis of the uninsured population.

PMID- 10199718
TI  - An outbreak of hepatitis A associated with an infected foodhandler.
AB  - OBJECTIVE: The recommended criteria for public notification of a hepatitis A
      virus (HAV)-infected foodhandler include assessment of the foodhandler's hygiene
      and symptoms. In October 1994, a Kentucky health department received a report of
      a catering company foodhandler with hepatitis A. Patrons were not offered immune
      globulin because the foodhandler's hygiene was assessed to be good and he denied
      having diarrhea. During early November, 29 cases of hepatitis A were reported
      among people who had attended an event catered by this company. Two local health
      departments and the Centers for Disease Control and Prevention, in collaboration
      with two state health departments, undertook an investigation to determine the
      extent of the outbreak, to identify the foods and event characteristics
      associated with illness, and to investigate the apparent failure of the criteria
      for determining when immune globulin (IG) should be offered to exposed members of
      the public. METHODS: Cases were IgM anti-HAV-positive people with onset of
      symptoms during October or November who had eaten foods prepared by the catering
      company. To determine the outbreak's extent and factors associated with illness,
      the authors interviewed all case patients and the infected foodhandler and
      collected information on menus and other event characteristics. To investigate
      characteristics of events associated with transmission, the authors conducted a
      retrospective analysis comparing the risk of illness by selected event
      characteristics. To evaluate what foods were associated with illness, they
      conducted a retrospective cohort study of attendees of four events with high
      attack rates. RESULTS: A total of 91 cases were identified. At least one case was
      reported from 21 (51%) of the 41 catered events. The overall attack rate was 7%
      among the 1318 people who attended these events (range 0 to 75% per event).
      Attending an event at which there was no on-site sink (relative risk [RR] = 2.3,
      95% confidence interval [CI] 1.4, 3.8) or no on-site kitchen (RR = 1.9, 95% Cl
      1.1, 2.9) was associated with illness. For three events with high attack rates,
      eating at least one of several uncooked foods was associated with illness, with
      RRs ranging from 8 to undefined. CONCLUSION: A large hepatitis A outbreak
      resulted from an infected foodhandler with apparent good hygiene and no reported
      diarrhea who prepared many uncooked foods served at catered events. Assessing
      hygiene and symptoms s subjective, and may be difficult to accomplish. The
      effectiveness of the recommended criteria for determining when IG should be
      provided to exposed members of the public needs to be evaluated.

PMID- 10199720
TI  - All quiet on the third coast: medical inspections of immigrants in Michigan.

PMID- 10199719
TI  - A community-wide infant mortality review: findings and implications.
AB  - The authors present the results of a community-wide infant mortality review,
      describe implications for the delivery of maternal and child health services, and
      discuss the value of such reviews in addressing local public health concerns. The
      review included an analysis of birth and death certificates and medical record
      data; maternal interviews; review of cases and development of recommendations by
      provider panels; and convening of community groups to develop strategies to
      improve the health and health care of women and infants. The review focused on
      287 infant deaths during 1990-1993. More than half of all neonatal deaths were
      attributable to "previable" or "borderline viable" births. Sexually transmitted
      infections were the most frequently identified underlying risk, and smoking was
      the most frequently identified prenatal risk. Homelessness, physical and sexual
      abuse, and alcohol use were at least twice as likely among women whose babies
      died than among a high risk comparison group. Panelists identified fragmented
      health care over the course of women's reproductive lives as a predominant theme.
      The authors conclude that: (a) The focus of maternal and child health care should
      shift to a model of women's health care that addresses the chronicity of social
      and clinical risks. (b) Infant mortality reviews are a valuable tool for
      community education, systems review, and policy development and can be applied to
      other public health issues with local significance. (c) Expectations about the
      review process's ability to produce conclusions about causality or
      recommendations narrowly geared to reducing infant mortality rates need to be
      reframed. (d) The model will be strengthened by greater participation of families
      affected by infant death.

PMID- 10199721
TI  - Havana revisited.

PMID- 10199722
TI  - The schools of public health and practice: where we stand.

PMID- 10199723
TI  - Genetic modification of liver grafts with an adenoviral vector encoding the Bcl-2
      gene improves organ preservation.
AB  - BACKGROUND: Liver function after transplantation is determined by the quality of
      the donor organ and the influences of preservation, flush, and reperfusion
      injury. In this regard, cell death (apoptosis) plays an important role in organ
      preservation and rejection. Therefore, we examined the possibility of genetic
      modification of the liver graft with a recombinant adenovirus vector encoding the
      Bcl-2 gene to reduce apoptosis during the preservation time. METHODS: Liver
      grafts from C57B1/6 mice were procured and preserved using standard techniques. A
      replication defective adenovirus vector (deltaE1) containing the human Bcl-2 gene
      (AdCMVhBcl-2) was developed in our laboratory. An adenovirus vector encoding an
      irrelevant gene (Escherichia coli beta-galactosidase) was used as a control. Each
      mouse received 1 x 10(9) plaque forming units administered i.v. 48 hr before the
      liver procurement. Analyses of liver enzyme activities were determined in the
      preservation solution. Apoptosis in liver biopsies was determined by DNA
      fragmentation with an in situ histochemical assay. RESULTS: Immunohistochemical
      analysis and RT-PCR confirmed the expression of hBcl-2 in the grafts. Grafts from
      livers expressing hBcl-2 showed significant reduction of the aspartame amino
      transferase (AST) and lactate dehydrogenase (LDH) release compared with grafts
      from the control groups. After rewarming, significant cytoprotection was also
      observed in grafts from animals treated with AdCMVhBcl-2. Histological analysis
      correlated with the hepatocellular injury determined with transaminases and LDH
      in the preservation solution. Significant reduction in the number of apoptotic
      cells was observed in grafts expressing hBcl-2. CONCLUSIONS: We have demonstrated
      a novel approach to reducing the preservation injury to liver grafts with the
      human Bcl-2 gene. This approach may allow a longer preservation time, potentially
      reduce the incidence of primary nonfunction, decrease the immunogenicity of the
      cold injured organ, and increase the safer use of "marginal" liver grafts.

PMID- 10199724
TI  - Fetal porcine islet-like cell clusters transplanted to cynomolgus monkeys: an
      immunohistochemical study.
AB  - BACKGROUND: The mechanism(s) involved in acute cellular xenograft rejection have
      hitherto been generated in vitro or in different experimental models, with pig
      tissue being transplanted to rodents. There is an urgent need to validate these
      results in a clinically more relevant combination of species. METHODS: Fetal
      porcine islet-like cell clusters (ICC) were transplanted under the kidney capsule
      in cynomolgus monkeys, either untreated or given immunosuppression with
      cyclosporine (CsA; 10 mg/kg body weight, intramuscularly) and 15-deoxyspergualin
      (DSG; 5 mg/kg body weight, intramuscularly). ICC xenografts were examined at 1,
      3, 6, or 10-12 days after transplantation, using immunohistochemical techniques.
      Serum levels of xenoreactive antibodies were measured with ELISA. RESULTS: No
      deposits of IgM, IgG, Clq, or C3 were detected within the ICC xenograft in any of
      the monkeys. Likewise, no significant increase in the levels of xenoreactive
      antibodies were found after transplantation. In untreated animals, a few N
      Elastase-positive cells (neutrophil granulocytes) were seen in the xenograft at
      day 1. A few mononuclear cells were present in the adjacent renal parenchyma, but
      they did not infiltrate the xenograft. At this time (day 1), early signs of
      necrosis were observed in the central parts of the graft. On day 3, the graft had
      a large, central necrotic area that contained polymorphonuclear cells; the
      remaining parts of the xenograft showed severe infiltration with CD8+ T cells.
      Occasional CD68+ cells (macrophages) were seen on days 1 and 3. On day 6, large
      numbers of macrophages were found infiltrating the entire graft. A few CD20+ B
      cells, accumulated as small clusters, were also found. Only a few natural killer
      cells (CD56+) were detected. The CsA/DSG-treated monkeys showed markedly fewer
      CD2+/CD8+ T cells on day 6 than the untreated monkeys, and the ICC graft was
      clearly better preserved. However, the number of CD8+ and CD68+ cells had
      increased considerably at 12 days after transplantation and diffusely infiltrated
      the whole ICC xenograft. CONCLUSION: Porcine ICC transplanted under the kidney
      capsule in cynomolgus monkeys were rejected by an acute cell-mediated rejection
      progressing during the first 6 days after transplantation. The process was not
      dependent on host Ig or C3 binding to the graft. Although the rejection of
      porcine ICC was significantly delayed in CsA/DSG-treated monkeys, the ICC
      xenografts were almost completely destroyed 12 days after transplantation.

PMID- 10199725
TI  - Involvement of endogenous interleukin-10 and tumor necrosis factor-alpha in renal
      ischemia-reperfusion injury.
AB  - BACKGROUND: Ischemia followed by reperfusion is a common clinical event
      associated with a pro-inflammatory response leading to organ dysfunction. The aim
      of the present study is to evaluate the interplay between this pro-inflammatory
      response and apoptosis. We investigated the role of the pro-inflammatory mediator
      tumor necrosis factor-alpha (TNF-alpha) and the anti-inflammatory mediator
      interleukin-10 (IL-10) in inflammation and apoptosis after renal ischemia
      reperfusion. METHODS: Male Swiss mice were subjected to 45 min of ischemia
      followed by reperfusion and subsequently administered neutralizing Abs against
      either TNF-alpha (TN3), IL-10 (JES5-2A5) or control. RESULTS: After 1 day of
      reperfusion, anti-TNF-alpha treatment reduced whereas anti-IL-10 treatment
      exacerbated postischemic renal injury, inflammation, and, to a lesser extent,
      apoptosis as measured by changes in blood urea nitrogen content,
      immunohistologically detectable renal TNF-alpha protein and neutrophils,
      histological integrity of renal parenchyma, and DNA ladder formation.
      Furthermore, anti-IL-10 treatment enhanced major histocompatibility complex class
      I and II expression at day 7 as measured by enzyme immunoassay and
      immunohistology. CONCLUSIONS: These data indicate that the extent of reperfusion
      induced apoptosis is modulated by the inflammatory response, during which locally
      produced TNF-alpha plays a significant role in the development of tissue injury.
      Subsequently, this pro-inflammatory reaction is followed by endogenous production
      of the anti-inflammatory cytokine IL-10, which serves as a physiological
      counterbalance to the effects of TNF-alpha. These novel pathophysiological
      insights may provide new basis for the development of tools for limiting ischemia
      and reperfusion injury.

PMID- 10199726
TI  - Efficacy of media enriched with nonlactate-generating substrate for organ
      preservation: in vitro and clinical studies using the cornea model.
AB  - BACKGROUND: Using a rabbit cornea model, our recent study demonstrated that Chen
      Medium (CM), an isotonic media enriched with nonlactate-generating high-energy
      substrates, is very effective for organ preservation. In the present study, the
      efficacy of CM is further evaluated with human corneas METHODS: The effectiveness
      of CM and Optisol for preserving the endothelial integrity of human corneas in
      vitro was evaluated by scanning electron microscopy. Clinical efficacy was
      evaluated in a total of 83 patients: 10 patients with keratoconus grafted
      randomly with either CM- or Optisol-stored cornea of the same donor, and 73
      patients with various conditions grafted with CM-stored corneas. After surgery,
      visual acuity and quality of the graft were monitored for up to 4.6 years.
      RESULTS: The scanning electron microscopic study revealed that after 11-day
      storage at 4 degrees C, the CM-stored cornea had only marginal disruptive
      changes, 9.4+/-1.1%, in endothelial cells, as opposed to 42.4+/-4.6% of the
      Optisol-stored cornea. All 78 CM-stored corneas, including 67 with 12.2- to 17.7
      hr death-to-storage time, 3-7.6 days of storage time, and initial marginal
      quality before storage, were successfully transplanted. These grafts were thin
      and clear, with an excellent epithelial integrity and without significant changes
      in endothelial cell density. Five Optisol-stored corneas were also successfully
      grafted; one of them, however, was edematous for about 4 weeks, and all the
      grafts were slightly thicker with substantial endothelial cell loss. CONCLUSION:
      Using a cornea model, present and recent studies show that CM is very effective
      for preserving tissue viability and endothelial integrity. Previous study
      revealed that CM-stored tissues maintained high levels of ATP and metabolic
      function, with suppression of lactate formation and accumulation. Thus, these
      findings support the concept that preservation of tissue viability is closely
      associated with the ability of the tissues to retain metabolic activity, to
      generate ATP efficiently, and to prevent acidosis effectively during storage.

PMID- 10199727
TI  - Antagonizing leukotriene B4 receptors delays cardiac allograft rejection in mice.
AB  - BACKGROUND: Allograft rejection is a cellular immunological/inflammatory response
      that is, in part, directed by potent proinflammatory mediators. This study was
      designed to test the hypothesis that leukotriene B4 (LTB4) may have a role in
      graft rejection and that LTB4 receptor antagonists may be clinically useful in
      the treatment of allograft rejection. METHODS: We evaluated the potent and
      selective LTB4 receptor antagonist CP-105696 in a murine heterotopic cardiac
      allograft model with oral dosing daily for 28 days or in an induction protocol
      (day -1 to day 3). RESULTS: At a dose of 50 mg/kg/day (28 days), B10.BR (H2k)
      allografts transplanted into C57Bl/6 (H2b) recipients were significantly
      protected, as reflected by the mean survival time versus control grafts (27+/-20
      days [n=10] vs. 12+/-6 days [n=14]; P=0.0146). Using an induction protocol (day 
      1 to day 3), CP-105696 at 100 mg/kg/day significantly prolonged allograft
      survival (33+/-23 days [n=9]; P=0.0026), but CP-105696 at 10 mg/kg/day did not
      (18+/-16 days [n=8]; P=0.1433). Syngeneic grafts survived indefinitely (n=11).
      Immunohistological evaluation of allografts at rejection revealed a mononuclear
      cell infiltrate composed primarily of CD3+ and CD11b+ (Mac-1+) cells, which were
      infrequent in syngeneic grafts. Allografts from mice treated with CP-105696 at 50
      or 100 mg/kg/day demonstrated a selective reduction in beta2-integrin (Mac-1)
      expression on monocytes/macrophages, as demonstrated by CD11b staining density
      compared with allograft controls. CONCLUSIONS: The results suggest that LTB4 or
      other potential ligands for LTB4 receptors may be important mediators of
      allograft rejection and support the clinical evaluation of LTB4 receptor
      antagonists in human organ transplantation.

PMID- 10199728
TI  - Co-encapsulation of Sertoli enriched testicular cell fractions further prolongs
      fish-to-mouse islet xenograft survival.
AB  - BACKGROUND: We previously demonstrated that alginate microencapsulation can
      prolong fish (tilapia) islet xenograft survival in diabetic animals. However, at
      present, microencapsulation does not provide complete immune protection to
      discordant islet xenografts, and long-term graft survival requires supplemental
      low-dose systemic immunosuppression. In the present study, fish islets were co
      encapsulated with Sertoli enriched testicular cell fractions to find out whether
      this would further prolong fish islet graft survival in diabetic mice. METHODS:
      Sertoli enriched testicular cell fractions were enzymatically harvested from
      adult Balb/c or Wistar-Furth rats. They were cultured and co-encapsulated with
      fragmented tilapia islets in alginate microcapsules. Encapsulated islets alone or
      islets co-encapsulated with Sertoli cells were then intraperitoneally
      transplanted into streptozotocin-diabetic Balb/c mice, and graft survival times
      were compared. Encapsulated and co-encapsulated islet function was also confirmed
      in streptozotocin-diabetic athymic nude mice. RESULTS: Co-encapsulation with
      Sertoli enriched testicular cell fractions further prolonged mean fish islet
      graft survival time from 21+/-6.7 days (encapsulated islet cells alone) to >46+/
      6.3 days (co-encapsulated with syngeneic murine Sertoli cells), without
      additional systemic immunosuppression. Testicular cells harvested from xenogeneic
      Wistar-Furth rats produced similar protective results (>46+/-10.9 days).
      CONCLUSIONS: Our results support the theory that Sertoli cells produce local
      immunosuppressive factors. These factors supplement the immune protective feature
      of alginate microcapsules in our model. Testicular cell fractions may be an
      important naturally occurring facilitator in the development of new
      microencapsulation systems for islet xenotransplantation.

PMID- 10199729
TI  - Morphologic alteration of hepatocytes and sinusoidal endothelial cells in rat
      fatty liver during cold preservation and the protective effect of hepatocyte
      growth factor.
AB  - BACKGROUND: Fatty liver grafts are considered to be one of the main factors of
      primary nonfunctioning graft in transplantation. We investigated here, the
      hepatic damage during cold preservation in a rat fatty liver model by
      ultrastructural observation, and examined the effect of human recombinant
      hepatocyte growth factor (hrHGF) on amelioration of the cold-preserved graft
      condition. METHODS: Wistar rats were fed a choline-deficient diet (CDD) for 7
      days. Livers were stored in cold University of Wisconsin (UW) solution for 0, 4,
      and 24 hr. We evaluated the ultrastructural alteration of the hepatocytes,
      sinusoidal architecture, and endothelial cells (SECs) by scanning and
      transmission electron microscopy. Ex vivo, we measured alanine aminotransferase
      (ALT) in first effluent as an index of hepatocyte injury and the hyaluronic
      uptake rate (HUR) as that of SEC damage. We injected hrHGF into rats fed CDD for
      7 days through the portal vein and also added it to the UW solution to determine
      whether or not the agent ameliorated the hepatic damage in cold-preserved fatty
      livers. RESULTS: In rats fed CDD for 7 days, the lesion occupied by fat deposits
      appeared to enlarge with the duration of cold preservation leading to the
      disarrangement of sinusoidal architecture. Furthermore, sinusoidal endothelial
      damage, in which gaps, blebs, microvilli, and sinusoid denudation were detected,
      appeared to be more severe in these livers than in the corresponding control
      livers. ALT significantly increased in the 4-hr cold-preserved livers of rats fed
      CDD for 7 days. HUR decreased with 4-hr cold preservation and/or with CDD
      feeding. Administration of hrHGF prevented the expansion of fatty droplets and
      reduced SEC injury as detected by morphological observations. Increase of ALT in
      first effluent was inhibited to about one fourth the level observed in the 4-hr
      cold-preserved livers of rats fed CDD. Moreover, HUR significantly increased with
      the pretreatment of hrHGF. CONCLUSION: The hepatic injury in both hepatocytes and
      SECs in cold-preserved fatty liver graft developed more rapidly and severely than
      in the corresponding controls and demonstrated a protective effect of hrHGF.

PMID- 10199730
TI  - Migration of dendritic cells to the draining lymph node after allogeneic or
      congeneic rat skin transplantation.
AB  - BACKGROUND: After transplantation, donor dendritic cells (DC) migrating to the
      draining lymph node of the recipient are thought to play an important role in the
      initiation of graft rejection. In this study, we compared the in vivo migration
      of DC after allogeneic skin transplantation with that after congeneic skin
      transplantation. METHODS: A rat model was used with the PVG-RT7b rats as donor
      animals. These rats have leukocytes bearing an epitope of the leukocyte common
      antigen that can be recognized by the monoclonal antibody His 41. The cells of
      the allogeneic (ACI) and congeneic (PVG) recipient animals do not express this
      marker. RESULTS: In both recipient rat strains, graft-derived His 41+ DC could be
      detected in the T cell areas of the draining lymph nodes after skin
      transplantation. However, the number of migrated His 41+ cells present was lower
      in the allogeneic recipients. Similar results were obtained when skin DC isolated
      from the PVG-RT7b rats were injected subcutaneously into the hind footpads of
      allogeneic and congeneic recipients. Although the numbers of migrated His 41+ DC
      present were lower, the lymph nodes of the allogeneic recipients were much more
      enlarged and the grafts were rejected which did not occur in the congeneic
      recipients. CONCLUSIONS: The presence of donor-derived DC in the graft draining
      lymph nodes underlines the importance of the direct route of allo-activation. The
      lower numbers of migrated His 41+ DC in lymph nodes of allogeneic recipients may
      be the result of killing of the cells after presentation of the allo-antigens to
      the recipient T cells.

PMID- 10199732
TI  - Bone marrow changes in heart transplant recipients with peripheral cytopenia.
AB  - BACKGROUND: We analyzed bone marrow changes in heart transplant recipients who
      develop peripheral cytopenia and underwent bone marrow biopsy (BMB). We
      correlated the changes in bone marrow with survival, acute and chronic rejection,
      infections, and malignancy. METHODS: The test group was constituted of 64 heart
      transplant recipients with peripheral cytopenia, in whom 82 BMBs were performed
      to assess marrow quantitative (cellularity, erythropoiesis, myelopoiesis,
      megakaryopoiesis, fibrosis, and blast cells) and qualitative (dyserythropoiesis,
      dysmyelopoiesis, and dysmegakaryopoiesis) changes. The control series was
      constituted of 217 matchable transplant recipients without cytopenia. Statistical
      analysis was aimed at assessing whether: (1) cytopenia is an independent risk
      factor for survival; (2) acute rejection, chronic rejection, infections, and
      malignancy predict cytopenia; (3) the degree in BMB change allows further
      stratification of the risk of death; and (4) characteristics and distribution of
      BMB lesions vary in patients with and without acute and chronic rejection,
      infections, and malignancy. RESULTS: In the test group, BMB specimens showed
      reduced cellularity in 68% of patients and dysplastic changes of a mild degree
      affecting all three marrow lines (erythropoietic in 88%, myelopoietic in 43%, and
      megakaryopoietic in 79%). At statistical analysis, peripheral cytopenia was an
      independent risk factor for survival, and malignancy proved to be a risk factor
      for cytopenia. Of BMB specimen changes, only dysmegakaryopoiesis showed a trend
      as a negative risk factor for survival. Acute rejection was associated with a
      high score of erythropoiesis, infections with a low score of dysmegakaryopoiesis,
      and malignancy with a high score of cellularity. CONCLUSIONS: Peripheral
      cytopenia is an independent risk factor for survival in heart transplant
      recipients. Different marrow changes correlate with transplantation-related
      complications, i.e., acute rejection, infection, and malignancy.

PMID- 10199731
TI  - Donor hematopoietic progenitor cells in nonmyeloablated rat recipients of
      allogeneic bone marrow and liver grafts.
AB  - BACKGROUND: Although the persistence of multilineage microchimerism in recipients
      of long-surviving organ transplants implies engraftment of migratory pluripotent
      donor stem cells, the ultimate localization in the recipient of these cells has
      not been determined in any species. METHODS: Progenitor cells were demonstrated
      in the bone marrow and nonparenchymal liver cells of naive rats and in Brown
      Norway (BN) recipients of Lewis (LEW) allografts by semiquantitative colony
      forming unit in culture (CFU-C) assays. The LEW allografts of bone marrow cells
      (BMC) (2.5x10(8)), orthotopic livers, or heterotopic hearts (abdominal site) were
      transplanted under a 2-week course of daily tacrolimus, with additional single
      doses on days 20 and 27. Donor CFU-C colonies were distinguished from recipient
      colonies in the allografts and recipient bone marrow with a donor-specific MHC
      class II monoclonal antibody. The proportions of donor and recipient colonies
      were estimated from a standard curve created by LEW and BN bone marrow mixtures
      of known concentrations. RESULTS: After the BMC infusions, 5-10% of the CFU-C in
      the bone marrow of BN recipients were of the LEW phenotype at 14, 30, and 60 days
      after transplantation. At 100 days, however, donor CFU-C could no longer be found
      at this site. The pattern of LEW CFU-C in the bone marrow of BN liver recipients
      up to 60 days was similar to that in recipients of 2.5x10(8) BMC, although the
      donor colonies were only 1/20 to 1/200 as numerous. This was expected, because
      the progenitor cells in the passenger leukocytes of a single liver are equivalent
      to those in 1-5x10(6) BMC. Using a liquid CFU-C assay, donor progenitor cells
      were demonstrated among the nonparenchymal cells of liver allografts up to 100
      days. In contrast, after heart transplantation, donor CFU-C could not be
      identified in the recipient bone marrow, even at 14 days. CONCLUSION: effective
      immunosuppression, allogeneic hematopoietic progenitors compete effectively with
      host cells for initial engraftment in the bone marrow of noncytoablated
      recipients, but disappear from this location between 60 and 100 days after
      transplantation, coincident with the shift of donor leukocyte chimerism from the
      lymphoid to the nonlymphoid compartment that we previously have observed in this
      model. It is possible that the syngeneic parenchymal environment of the liver
      allografts constitutes a privileged site for persistent progenitor donor cells.

PMID- 10199733
TI  - Reversal of naturally occuring diabetes in primates by unmodified islet
      xenografts without chronic immunosuppression.
AB  - BACKGROUND: Isolated pancreatic islet transplantation (IPITx) is an attractive
      alternative for treatment of insulin-dependent diabetes mellitus (IDDM). However,
      IPITx has been difficult to implement clinically because islets frequently fail
      to function, have a high incidence of rejection, and are susceptible to
      autoimmune recurrence and damage by chronic immunosuppressive therapy. Tolerance
      induction may be a rational approach to resolve several of these limitations.
      Because anti-CD3 immunotoxin (IT) has been successful in promoting stable primate
      kidney transplant tolerance in our experience, we considered that tolerance
      induction with IT might be duplicated in IPITx. MATERIALS AND METHODS: Three
      monkeys with spontaneous IDDM (two Macaca fascicularis and one Ceropithecus
      aethiops) were treated with xenogeneic pancreatic islets (Macaca mulatta).
      Intrahepatic islet transplantation was performed at a mean of 13136+/-3860 islet
      equivalents/kg. Islet xenograft acceptance was accomplished by tolerance
      induction with two injections of IT given on day 0 at 2 hr before transplantation
      and on day +1, respectively. IT treatment was supplemented with cyclosporine and
      steroids administered on days 0 through 4. No additional immunosuppression was
      given thereafter. Two additional control macaques with spontaneous IDDM received
      the immunosuppressive protocol without islet infusion. RESULTS: All recipients
      were restored to stable euglycemia, off exogenous insulin, within 1-2 weeks after
      transplantation. Glucose tolerance, C-peptide, and glycosylated hemoglobin tests
      confirmed the restoration of normal glucose homeostasis after islet
      transplantation. All three islet recipients have remained euglycemic at 410, 255,
      and 100 days of follow-up despite recovery of peripheral T cells to normal
      levels. In contrast, none of the controls presented changes in the diabetic
      status 4 and 8 months after treatment. CONCLUSIONS: These results represent the
      first demonstration in nonhuman primates of stable, long-term acceptance of
      nonencapsulated xenogeneic islets off all immunosuppression, suggesting
      operational tolerance. The findings have potential implications for islet
      transplantation as well as improved and more cost-effective therapy for IDDM.

PMID- 10199734
TI  - CD8+ T cells produce RANTES during acute rejection of murine allogeneic skin
      grafts.
AB  - BACKGROUND: Based on their chemoattractant properties, it is likely that
      chemokines play a role in recruiting alloantigen-primed T cells to allografts and
      in amplifying inflammation within the graft. The graft-infiltrating leukocytes
      producing specific chemokines remain largely unknown. METHODS: We tested the
      intragraft RNA expression of the chemokine RANTES (regulated on activation normal
      T expressed and secreted) and granzyme B during rejection of full thickness,
      allogeneic skin grafts by C57BL/6 mice. Grafts with different immunogenetic
      disparities were chosen to test expression when rejection was mediated by CD4+,
      CD8+, or both CD4+ and CD8+ T cells. RNA expression was also tested in purified
      CD4+ and CD8+ T cell populations from skin graft recipients. Immunohistology was
      performed on graft sections to test colocalization of RANTES protein and graft
      infiltrating CD4+ and CD8+ T cells. RESULTS: Intra-allograft RANTES RNA
      expression was not observed during CD4+ T cell-mediated rejection. Expression of
      RANTES and granzyme B RNA was observed at low levels in purified populations of
      CD8+, but not CD4+, T cells from the spleen and lymph nodes of graft recipients
      beginning at day 7 after transplantation and increased thereafter. Intra
      allograft RANTES protein was associated with a small number of graft-infiltrating
      CD8+ T cells but was also associated with endothelial cells and with many graft
      infiltrating CD4+ T cells. CONCLUSIONS: CD8+ T cells produce RANTES during
      allogeneic skin graft rejection. In the allograft, the chemokine also colocalizes
      with CD4+ T cells that do not produce RANTES.

PMID- 10199735
TI  - Definition and characterization of chicken Gal alpha(1,3)Gal antibodies.
AB  - BACKGROUND: The Gal alpha(1,3)Gal epitope is of interest as, in pig-to-primate
      xenotransplantation, it is the major target of naturally occurring human IgM and
      IgG antibodies, leading to hyperacute rejection. Human and Old World monkeys make
      anti-Gal alpha(1,3)Gal antibodies as they lack a functional gene and do not
      express Gal alpha(1,3)Gal. Interestingly, the cultured fibroblasts of some other
      species, such as chickens, have been reported also not to express Gal
      alpha(1,3)Gal--if this is true for other tissues, and chickens do not express Gal
      alpha(1,3)Gal antigen, then they would have anti-Gal antibodies--which could have
      diagnostic and therapeutic value, particularly as chicken antibodies do not fix
      mammalian complement. METHODS: Standard serological methods were used to
      characterize the antibodies. Several baboons received pig kidney xenografts that
      had been perfused with hyperimmune chicken anti-Gal antibodies. RESULTS AND
      CONCLUSIONS: We now demonstrate that chickens do not express Gal alpha(1,3)Gal on
      their red cells, leukocytes, or tissues, and that their serum contains large
      amounts of anti-Gal alpha(1,3)Gal antibodies. In addition, chickens could be
      immunized to produce high-titer, high-avidity antibodies (9.5x10(9) M(-1))--an
      avidity considerably greater than that of the Gal alpha(1,3)Gal binding lectin
      IB4 (2.9x10(8) M(-1)) or Gal antibodies in human serum (2.2x10(5) M(-1)). Chicken
      antibodies, obtained from both normal and immunized chickens, could block the in
      vitro cytolysis of pig endothelial cells or lymphocytes by human or baboon
      antibodies. However, such antibodies tested in vivo in pig-to-baboon
      xenotransplantation failed to block hyperacute rejection and, indeed, may have
      accelerated this.

PMID- 10199736
TI  - Anti-CD25 therapy reveals the redundancy of the intragraft cytokine network after
      clinical heart transplantation.
AB  - BACKGROUND: Despite blockade of the interleukin-2/interleukin 2 receptor (IL-2/IL
      2R) pathway by the murine anti-CD25 (i.e., IL-2R alpha chain) monoclonal antibody
      BT563, cardiac rejection can still occur. In these cases, growth factors other
      than IL-2 may contribute to allograft rejection. We studied the expression of IL
      15, a macrophage-derived cytokine associated with T-cell activation, which
      interacts with the beta and gamma chains of the IL-2R during rejection episodes
      under anti-CD25 therapy. METHODS: We measured intragraft IL-15 mRNA expression
      and the number of IL-15- and CD68-positive cells in posttransplantation
      endomyocardial biopsies (EMBs; n=45) and in nontransplanted, donor-heart
      specimens (n=11) by competitive template reverse transcription-polymerase chain
      reaction and immunohistochemistry, respectively. RESULTS: IL-15 mRNA expression
      was present in the majority of posttransplantation EMB specimens (91%, 41/45) and
      in nontransplanted donor-heart specimens (91%, 10/11). Relative IL-15 mRNA levels
      were neither associated with transplantation nor with rejection status. After
      transplantation, the number of IL-15- and CD68-positive cells significantly
      increased (P<0.001), but IL-15-positive cell counts did not reflect the
      histological rejection grade. Anti-CD25 treatment, in contrast to its effects on
      the IL-2/IL-2R complex, had no influence on intragraft IL-15 mRNA and protein
      production. In rejection EMB specimens, during (n=5) and after (n=8) anti-CD25
      therapy, no differences in relative IL-15 mRNA levels, or in IL-15- and CD68
      positive cell counts, were measured. CONCLUSIONS: After heart transplantation,
      high numbers of IL-15- and CD68-positive cells infiltrate the graft. This
      phenomenon is independent of the rejection status. IL-15 remains present during
      blockade of the IL-2/IL-2R pathway by anti-CD25 monoclonal antibodies, and it may
      participate in T cell-dependent donor-directed immune responses, thereby
      explaining the occurrence of rejection in the absence of IL-2.

PMID- 10199737
TI  - Interleukin-10 and posttransplant lymphoproliferative disorder after kidney
      transplantation.
AB  - BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) is a life
      threatening complication of transplantation, which comprises a morphologically
      and clinically heterogeneous spectrum of B-lymphocyte diseases. Risk factors
      include primary or reactivated Epstein-Barr virus (EBV) infection, and the type
      and duration of immunosuppression. Interleukin-10 (IL-10) is a pleiotropic
      cytokine, produced primarily by T-helper 2 (Th2) lymphocytes in the later stages
      of T-cell activation, suggested to play a role in EBV-associated PTLD. We
      recently reported preliminary findings on IL-10 in relation to the development of
      PTLD in three kidney transplanted patients. The study now includes nine patients
      that could be followed before and/or after the occurrence of lymphoma. METHODS:
      Nine patients with lymphomas (eight PTLDs and one Hodgkin's disease) were
      diagnosed among 268 consecutive renal transplantations (1990-1997). All were
      treated with cyclosporine with an initial 10-day course of antilymphocyte
      globulin, supplemented from 1995 with mycophenolate mofetil. Serum antibodies
      against EBV were detected using recombinant antigens. A double sandwich enzyme
      linked immunosorbent assay using rabbit antibodies to purified human recombinant
      IL-10 was employed; the assay is specific for human natural and viral IL-10.
      RESULTS: Three patients experienced primary EBV infection, five reactivated EBV
      infections, and one did not change EBV status. Three patients had a fulminant
      course and died with EBV-associated PTLD confirmed post mortem. The other six are
      alive and are apparently cured. Treatment was immediate discontinuation of
      immunosuppression (in all PTLDs) and long-term high-dose aciclovir in all but
      one. Two patients have maintained excellent graft function for 3 and 2 years,
      respectively, without immunosuppression and are now in a state of operational
      tolerance. In three of four cases with initial lymphoma, EBV infection (primary
      or reactivation) preceded the increase in IL-10. In all four cases, the IL-10
      increase preceded the PTLD diagnosis. In six cases, IL-10 could be followed after
      treatment showing either immediate zero or a decrease to zero. CONCLUSION: IL-10
      seems to play a role in EBV-associated PTLD. Moreover, IL-10 may have an
      important role in transplant tolerance by inducing long-lasting anergy to donor-
      and host-specific alloantigens, perhaps caused by down-regulation of Th1
      cytokines in the graft. If substantiated, this may provide new insight into the
      pathogenesis of PTLD introducing new strategies for prevention and therapy of
      PTLD, and for the induction of tolerance in transplanted patients.

PMID- 10199738
TI  - Transforming growth factor (TGF)-beta mimics and anti-TGF-beta antibody abrogates
      the in vivo effects of cyclosporine: demonstration of a direct role of TGF-beta
      in immunosuppression and nephrotoxicity of cyclosporine.
AB  - BACKGROUND: Cyclosporine (CsA) has been shown to induce the expression of
      transforming growth factor (TGF)-beta both in vitro and in vivo. It is
      hypothesized that the efficacy as well as the side effects of CsA are mediated by
      TGF-beta. This study was planned to investigate whether anti-TGF-beta mitigated
      and TGF-beta reproduced the in vivo effects of CsA to directly prove this
      hypothesis. METHODS: B6AF1 (H2b/k.d) mice were divided into groups and received
      the following: CsA, vehicle (olive oil), CsA + anti-TGF-beta1 antibody, TGF
      beta1, or vehicle phosphate-buffered saline/bovine serum albumin. All studies
      were carried out at 10 and 28 days after the last day of CsA administration with
      the exception of the exogenous TGF-beta experiments, which were performed 5 days
      after exogenous TGF-beta administration. The efficacy was studied by the anti-CD3
      induced ex vivo proliferation of splenocytes measured by [3H]thymidine uptake;
      TGF-beta protein levels were quantified by ELISA. TGF-beta, collagen, and
      fibronectin gene expression was studied using reverse transcriptase-polymerase
      chain reaction, and histopathological analysis was made on periodic acid-Schiff-
      and trichrome C-stained thin kidney sections. RESULTS: CsA treatment resulted in
      decreased ex vivo proliferation of splenocytes, an increase in TGF-beta protein
      in the sera, and renal histopathological changes including tubular swelling,
      vacuolization, thrombotic microangiopathy, and increased expression of TGF-beta,
      collagen and fibronectin genes. All of these findings were blocked by anti-TGF
      beta antibody. CONCLUSION: The study demonstrates the in vivo modulation of the
      effects of CsA by manipulating TGF-beta levels and suggests that TGF-beta at
      least in part mediates CsA's beneficial and detrimental effects.

PMID- 10199739
TI  - Allogeneic bronchoalveolar lavage cells induce the histology and immunology of
      lung allograft rejection in recipient murine lungs: role of intercellular
      adhesion molecule-1 on donor cells.
AB  - BACKGROUND: Intercellular adhesion molecule (ICAM)-1 expressed on accessory cells
      has a key role in antigen presentation. The histology and immunology of lung
      allograft rejection is postulated to result from donor lung accessory cells
      presenting alloantigens to recipient lymphocytes, and, therefore, ICAM-1 may have
      a crucial role in the rejection process. We have previously reported that the
      instillation of allogeneic (C57BL/6, I-a(b)) bronchoalveolar lavage (BAL) cells
      (96% macrophages, 2% dendritic cells) into the lungs of recipient BALB/c mice (I
      a(d)) induced the histology and immunology of acute lung allograft rejection.
      Using this model, the purpose of the current study was to determine the role of
      ICAM-1 on donor lung cells in lung allograft rejection. METHODS: BALB/c mice
      received allogeneic BAL cells from wild-type or ICAM-1 mutant (lacking ICAM-1
      expression) C57BL/6 mice by nasal insufflation weekly for 4 weeks. Recipient mice
      underwent BAL and serum collection for the determination of T helper 1/T helper 2
      cytokines and IgG subtypes. Lung histology was graded using standard criteria for
      allograft rejection. RESULTS: Although wild-type cells induced a lymphocytic
      vasculitis and bronchitis, ICAM-1 mutant allogeneic BAL cells only induced a
      lymphocytic vasculitis in recipient lungs. Both wild-type and ICAM-1 mutant cells
      induced up-regulated local interferon-gamma and IgG2a production, and deposition
      of IgG2a in recipient lungs. CONCLUSIONS: These data show that ICAM-1 on donor
      lung accessory cells mediates differential effects on the histology and
      immunology of acute lung allograft rejection.

PMID- 10199740
TI  - Human allogeneic vascular rejection after arterial transplantation and peripheral
      lymphoid reconstitution in severe combined immunodeficient mice.
AB  - BACKGROUND: Interspecies differences create important shortcomings in existing
      animal models used to describe in vivo events responsible for allograft
      rejection. Alloimmune destruction of human dermal microvessels, histologically
      consistent with rejection, has been demonstrated in human skin-grafted severe
      combined immunodeficient (SCID) mice receiving allogeneic human peripheral blood
      mononuclear cells (PBMC). We have now documented human alloimmune injury in a
      vascularized, SCID-human arterial transplantation model. METHODS: Fresh human
      artery was used to replace the CB.17 SCID/beige mouse infrarenal aorta. Seven
      days later, 3x10(8) human PBMC were administered intraperitoneally, and
      lymphocyte engraftment was considered successful when circulating human CD3+
      cells were later identified in peripheral blood. RESULTS: Forty-six of 49 (94%)
      mice undergoing transplantation survived, including 14 controls with arterial
      grafts receiving no PBMC. Twenty-eight of 32 mice demonstrated circulating human
      CD3+ cells, 14 days after PBMC administration. Animals were killed at 14, 21, or
      28 days after receiving allogeneic PBMC, and arteries were recovered for
      histology and immunohistology. All 14 control mice had patent transplanted grafts
      with normal vascular histology and no lymphoid infiltration. Damage to
      transplanted arteries among lymphocyte-engrafted mice was apparent by 14 and 21
      days in some animals, whereas 16 of 22 exhibited moderate to severe intimal,
      medial, and/or adventitial lymphocytic infiltration with intimal expansion by day
      28. The infiltrate consisted of HLA-A, -B, -C+, and -DR+, human CD3+ cells,
      approximately equally distributed as CD4+ and CD8+ subsets. Some infiltrating
      lymphocytes were cytolytic cells as demonstrated by perforin staining. The
      endothelium of transplanted human arteries exhibited endothelialitis, and the
      endothelial cells stained intensely with anti-HLA-A, -B, -C and anti-HLA-DR
      antibodies. The expanded intima was predominantly smooth muscle cells, staining
      positively for smooth muscle alpha-actin, HLA-A, -B, -C and HLA-DR. Medial
      necrosis was not observed. CONCLUSION: The results provide evidence of alloimmune
      mediated vascular rejection in this human arterial transplantation model.

PMID- 10199741
TI  - Alloimmune-mediated apoptosis: comparison in mouse models of acute and chronic
      cardiac rejection.
AB  - BACKGROUND: The purpose of the present study was (1) to compare apoptotic
      activity in models of acute and chronic rejection and (2) to study the cellular
      distribution of parenchymal versus inflammatory cell apoptosis. METHODS:
      Heterotopic cardiac mouse transplantation (CBA into C57BL/6) was used to produce
      allografts undergoing acute (day 7, untreated recipients, n=6) or chronic (day
      55, anti-CD4/8 for 28 days, n=6) rejection. As references, we used 55-day
      isograft controls (n=5) and native hearts (n=6). To assess apoptotic activity, we
      quantified DNA laddering (32P incorporation), DNA fragmentation (antinucleosome
      ELISA), and caspase-1 transcript levels (32P-reverse transcriptase-polymerase
      chain reaction). To localize apoptosis, we performed terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labeling. RESULTS: DNA laddering and
      nucleosome levels were increased in allografts undergoing acute or chronic
      rejection when compared with both controls. Both parameters were twofold higher
      in acutely compared with chronically rejecting hearts. Caspase-1 transcript
      levels were increased in acutely (P<0.0001) and chronically rejecting hearts
      (P=0.004). Acutely rejecting grafts had more terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labeling-positive nuclei (53+/-3 nuclei/high
      powered field) than chronically rejecting grafts (9+/-1 nuclei/high-powered
      field, P<0.0001), but the distribution between graft-infiltrating inflammatory
      cells and myocytes was similar. Vascular cells undergoing apoptosis were
      infrequent in both forms. CONCLUSION: Using four separate indices, apoptotic
      activity is more pronounced in cardiac allografts undergoing acute compared with
      chronic rejection. This reflects, in part, the degree of alloimmune response.
      However, we speculate that the contributions of apoptosis to various forms of
      rejection are multifactorial. The long-term outcome to the graft may depend upon
      the magnitude, timing, and target of programmed cell death.

PMID- 10199742
TI  - Immunomodulatory functions of hyaluronate in the LEW-to-F344 model of chronic
      cardiac allograft rejection.
AB  - BACKGROUND: CD44 is an important leukocyte cell surface glycoprotein with diverse
      functions including cell adhesion, homing, migration, and activation. METHODS:
      Because administration of the principal ligand of CD44, hyaluronate (HA), in
      soluble form, can inhibit CD44-HA interaction, we tested the effects of HA in
      vivo in an established model of chronic allograft rejection. Control F344
      recipients of LEW hearts received either no treatment or low-dose cyclosporine
      (CsA) for 30 days from the day of transplantation. Experimental animals received
      30 days of CsA in combination with 30 or 90 days of low molecular weight HA (LMW
      HA). RESULTS: CsA therapy alone resulted in approximately 40% long-term (>100
      days) graft survival, whereas CsA + LMW-HA (30-day and 90-day protocols)
      significantly increased long-term graft survival to 60% and 92%, respectively.
      Light microscopy and immunohistology of CsA-treated and CsA + LMW-HA-treated
      grafts harvested at day 30 after transplantation demonstrated that LMW-HA + CsA
      therapy decreased mononuclear cell infiltration and afforded better preservation
      of myocardial architecture. In addition, LMW-HA + CsA-treated grafts exhibited
      decreased expression of interferon-gamma and the growth factors transforming
      growth factor-beta, platelet-derived growth factor, and fibrogenic growth factor
      beta. Long-term surviving grafts were assessed for arteriosclerosis, the sine qua
      non of chronic rejection in this model. Using a standardized scoring system,
      significantly less arteriosclerosis was seen in grafts from LMW-HA + CsA-treated
      animals at 120 days after transplantation compared with CsA alone-treated grafts.
      This difference was not significant, however, in grafts harvested at >150 days.
      CONCLUSION: This is the first report indicating that CD44-HA interactions play an
      important role in chronic allograft rejection.

PMID- 10199743
TI  - Successful living related simultaneous pancreas-kidney transplant between
      identical twins.
AB  - Simultaneous pancreas-kidney transplant from living donors has been recently
      proposed as an effective therapeutic option in selected uremic patients with type
      I diabetes. We report the first simultaneous pancreas-kidney transplant performed
      between identical twins. Posttransplant, the recipient has been maintained on low
      dose cyclosporine to avoid recurrent auto-immune insulitis. At the 1-year follow
      up, both donor and recipient are well with normal renal function and excellent
      glucose control. Simultaneous pancreas-kidney transplant between identical twins
      can be performed successfully using cyclosporine to prevent recurrent auto-immune
      insulitis.

PMID- 10199744
TI  - Polyomavirus disease under new immunosuppressive drugs: a cause of renal graft
      dysfunction and graft loss.
AB  - BACKGROUND: Manifest polyomavirus (PV) renal graft infection is a rare
      complication. We diagnosed 5 cases among 70 kidney recipients undergoing
      transplants since December 1995; however, there were no cases at our institution
      before December 1995. METHOD: To identify risk factors promoting manifest PV
      graft infection, we compared those 5 patients with kidney recipients who had
      signs of PV replication but no manifest graft infection (n=23, control group). PV
      replication was judged by the presence of intranuclear inclusion cells in the
      urine. RESULTS: Before the infection, five of five patients had recurrent
      rejection episodes. All were switched from cyclosporine A to high dose tacrolimus
      as rescue therapy. Infection was diagnosed histologically 9+/-2 months
      posttransplantation; it persisted and led to graft loss in four of five patients.
      In control patients, graft function was stable, 1 of 23 patients were switched to
      tacrolimus as rescue therapy, and graft loss occurred in 4 of 23 patients.
      CONCLUSION: Recurrent rejection episodes and high dose immunosuppressive therapy,
      including tacrolimus, are risk factors for manifest PV kidney graft infection,
      which has an ominous prognosis.

PMID- 10199745
TI  - The value of intravenous heme-albumin and plasmapheresis in reducing
      postoperative complications of orthotopic liver transplantation for
      erythropoietic protoporphyria.
AB  - Erythropoietic protoporphyria (EPP) is marked by a deficiency of ferrochelatase,
      which occurs in all cells and tissues, preventing effective conversion of proto
      porphyrin IX to heme and thereby blocking effective feedback inhibition of heme
      synthesis. The major source of the excess protoporphyrin is the bone marrow.
      Protoporphyrin IX may accumulate, with resultant toxicity chiefly of the marrow,
      skin, nervous system, and liver. Orthotopic liver transplantation (OLT) is, at
      present, the only adequate intervention for severe liver compromise secondary to
      protoporphyrin deposition, but it has been complicated by severe photosensitivity
      and polyneuropathy. Intravenous heme and plasmapheresis have been proposed but
      not previously reported as means to reduce the protoporphyrin burden before liver
      transplantation. We report a man with EPP who underwent preoperative heme-albumin
      administration and plasmaphereses that led to marked reductions in plasma and
      erythrocyte protoporphyrin levels. His OLT was uneventful, and he developed
      neither polyneuropathy nor exacerbation of photosensitivity.

PMID- 10199746
TI  - Vascular endothelial growth factor expression in human chronic renal allograft
      rejection.
AB  - BACKGROUND: Chronic renal allograft rejection is characterized by interstitial
      fibrosis and vasculopathy. Vascular endothelial growth factor (VEGF) is an
      endothelial mitogen with increased expression in inflammation and vasculopathy.
      METHODS: Renal tissue from 17 patients with chronic rejection was examined for
      VEGF protein and the presence of CD 68-positive macrophages, and compared to
      biopsies from patients with temporary allograft dysfunction, acute rejection, and
      native kidneys with thin membrane disease. RESULTS: In the chronic rejection
      group, there was markedly increased expression of VEGF protein in the
      interstitium (P<0.0001). In serial sections, VEGF colocalized with the expression
      of CD 68-positive macrophages. Significantly more macrophages were in the
      tubulointerstitium in tissue with chronic rejection than in those with temporary
      allograft dysfunction (P<0.005). Additionally, VEGF protein expression in the
      glomeruli and the vascular compartment of patients with chronic rejection was
      increased. CONCLUSION: The up-regulation of VEGF in chronic renal allograft
      rejection may be important in inflammation and development of fibrosis.

PMID- 10199747
TI  - Clinical review 102: Type 2 diabetes mellitus: update on diagnosis,
      pathophysiology, and treatment.

PMID- 10199748
TI  - A mathematical model for predicting growth response to growth hormone replacement
      therapy--a useful clinical tool or an intellectual exercise?

PMID- 10199749
TI  - Derivation and validation of a mathematical model for predicting the response to
      exogenous recombinant human growth hormone (GH) in prepubertal children with
      idiopathic GH deficiency. KIGS International Board. Kabi Pharmacia International
      Growth Study.
AB  - Postmarketing surveillance studies of recombinant human GH therapy, such as the
      Kabi Pharmacia International Growth Study (KIGS; Pharmacia & Upjohn, Inc.,
      International Growth Database), have accumulated extensive data concerning the
      characteristics and growth outcomes of children with various causes of short
      stature. These data provide an opportunity to analyze the factors that determine
      responsiveness to GH and allow the development of disease-specific growth
      prediction models. We undertook a multiple regression analysis of height velocity
      (centimeter per yr) with various patient parameters of potential relevance using
      data from a cohort of 593 prepubertal children with idiopathic GH deficiency
      (GHD) from the KIGS database. Our aim was to produce models that would have
      practical utility for predicting prepubertal growth during each of the first 4 yr
      of GH replacement therapy. These models were validated by a prospective
      comparison of predicted and observed growth outcomes in an additional 3 cohorts
      of prepubertal children with idiopathic GHD: 237 additional KIGS patients, 29
      patients from the Australian OZGROW study, and 33 patients from Tubingen,
      Germany. The most influential variable for first year growth response was the
      natural log (ln) of the maximum GH response during provocation testing, which was
      inversely correlated with height velocity. The first year growth response was
      also inversely correlated with chronological age and height SD score minus
      midparental height SD score. First year growth was positively correlated with
      body weight SD score, weekly GH dose (ln), and birth weight SD score. Two first
      year models were developed using these parameters, 1 including and 1 excluding
      the maximum GH response to provocative testing. The former model explained 61% of
      the response variability, with a SD of 1.46 cm; the latter model explained 45% of
      the variability, with a SD of 1.72 cm. The two models gave similar predictions,
      although the model excluding the maximum GH response to testing tended to
      underpredict the growth response in patients with very low GH secretory capacity.
      For the second, third, and fourth year growth responses, 4 predictors were
      identified: height velocity during the previous year (positively correlated),
      body weight SD score (positively correlated), chronological age (negatively
      correlated), and weekly GH dose (ln; positively correlated). The models for the
      second, third, and fourth year responses explained 40%, 37%, and 30% of the
      variability, respectively, with SDs of 1.19, 1.05, and 0.95 cm, respectively.
      When the models were applied prospectively to the other cohorts, there were no
      significant differences between observed and predicted responses in any of the
      cohorts in any year of treatment. The fourth year response model gave accurate
      prospective growth predictions for the fifth to the eighth prepubertal years of
      GH treatment in a subset of 48 KIGS patients. Analyses of Studentized residuals
      provided further validation of the models. The parameters used in our models do
      not explain all of the variability in growth response, but they have a high
      degree of precision (low error SDs). Moreover, the parameters used are robust and
      easily accessible. These properties give the models' practical utility as growth
      prediction tools. The availability of longitudinal, disease-specific models will
      be helpful in the future for enabling growth-promoting therapy to be planned at
      the outset, optimized for efficacy and economy, and individualized to meet
      treatment goals based on realistic expectations.

PMID- 10199750
TI  - Tumor localization--the ectopic ACTH syndrome.

PMID- 10199751
TI  - Lack of utility of (111)In-pentetreotide scintigraphy in localizing ectopic ACTH
      producing tumors: follow-up of 18 patients.
AB  - Octreotide scintigraphy has been advocated as the principal imaging modality for
      localizing ectopic ACTH-secreting tumors in Cushing's syndrome. To assess its
      usefulness we reviewed the course of 18 consecutive patients with ectopic ACTH
      producing tumor. Imaging included (111)In-pentetreotide scintigraphy, computed
      tomography (CT), and/or magnetic resonance imaging (MRI). Tumor was detected
      initially in 7/18 patients, and in 3/18 during follow-up. No ACTH-secreting tumor
      was detected by octreotide scintigraphy when CT/ MRI were negative. Seventeen of
      forty octreotide scintigrams were abnormal. CT and/or MRI confirmed tumors in 10,
      but demonstrated nonendocrine lesions in association with 6 false positive
      octreotide scintigrams. Hepatic venous sampling for ACTH refuted one lesion
      detected by octreotide and CT scans. Twenty-three of forty octreotide scintigrams
      were normal. Of these, 8 were false negative, as CT and/or MRI detected tumor; 10
      agreed with negative CT and MRI, and 5 correctly refuted false positive CT and/or
      MRI scans. Repeated CT/ MR, but not octreotide scintigraphy, led to tumor
      resection in 2 patients. We conclude that octreotide scintigraphy does not offer
      greater sensitivity than CT/MRI and that false positive scans are common.
      Although octreotide scintigraphy may be helpful in selected cases, it is not a
      significant advance over conventional imaging for ectopic ACTH-secreting tumors.

PMID- 10199752
TI  - Usefulness of somatostatin receptor scintigraphy in patients with occult ectopic
      adrenocorticotropin syndrome.
AB  - SRIF receptor scintigraphy (SRS) has been proposed for the localization of
      ectopic ACTH-secreting tumors responsible for Cushing's syndrome. However, in
      most cases reported, the tumors were also visible using conventional imaging.
      Therefore, the usefulness of SRS in localizing truly occult ectopic ACTH
      secreting tumors remains unknown. We report the results of SRS in 12 patients
      with ectopic ACTH syndrome (EAS) and in whom the source of ACTH was occult at
      presentation despite carefully performed conventional imaging. The diagnosis of
      EAS was made by identification of an ACTH-secreting tumor during follow-up in 5
      patients or given a pituitary-to-peripheral ACTH ratio of 1.9 or less during
      petrosal sinus sampling combined with CRH injection and a negative pituitary
      magnetic resonance imaging (MRI). Whole-body planar SRS, using (111)In
      pentetreotide, was performed 19 times in the 12 patients during initial workup
      and/or follow-up. Axial tomography imaging (single-photon emission-computed
      tomography) was performed in 7 of these. Conventional imaging was performed
      within a month of SRS, allowing comparison of the two approaches for the
      localization of the ACTH-secreting tumors. In addition, the response of plasma
      cortisol, after a single injection of 200 microg octreotide, was studied in 6
      patients. Five patients had negative SRS and conventional imaging studies. The
      source of ACTH secretion remains occult despite 10-55 months of follow-up in four
      of these, whereas a 2-cm ileal carcinoid tumor, with liver micrometastases, was
      found at laparotomy in one patient, 14 months after presentation. SRS was
      positive in 4 of 12 patients. It was false-positive in 1 patient with follicular
      thyroid adenoma. Nineteen months after presentation, SRS identified liver
      metastasis that was also visible using MRI in one patient, but the primary tumor
      remains occult. SRS identified a 10-mm pancreatic tumor that became detectable,
      using computed tomography (CT) scanning 9 months later, in 1 patient; and 2
      mediastinal lymph nodes of 10 mm, previously ignored by MRI, in another patient,
      whereas no tumor was detectable within the parenchymal lung. SRS had little
      influence on therapeutic options in these 2 patients, in whom no final diagnosis
      could be made. Repetition of SRS during the follow-up of patients with previously
      negative scintiscans was useless. Conventional imaging was positive in 6 of 12
      patients. In the 2 patients with pancreatic tumor and isolated mediastinal lymph
      nodes, conventional imaging studies were interpreted as positive only after the
      results of SRS. One patient had liver metastasis that was also visible using SRS.
      Thin-section CT scanning visualized ACTH-secreting bronchial tumors and
      metastatic mediastinal lymph nodes of 10-15 mm in diameter in 3 patients after 14
      72 months of follow-up, whereas SRS was negative. There was no evident
      relationship between the endocrine status (hyper- or eucortisolism) and the
      results of SRS. The in vivo response of plasma cortisol to octreotide correlated
      to the results of SRS in 4 of 6 cases. In conclusion, both imaging procedures had
      a low diagnostic yield in this series. However, the sensitivity of SRS for the
      detection of bronchial carcinoids was lower than that of thin-section CT
      scanning. We therefore advocate the use of conventional imaging, including thin
      section CT scanning of the chest, analyzed by experienced radiologists, as the
      first-line investigation in patients with occult EAS. SRS should not be repeated
      during the follow-up in patients with a previously negative scintigram.

PMID- 10199753
TI  - Prevention of recurrent pancreatitis in familial lipoprotein lipase deficiency
      with high-dose antioxidant therapy.
AB  - We describe a dramatic response to antioxidant therapy in three patients with
      familial lipoprotein lipase deficiency complicated by frequent severe episodes of
      pancreatitis who had failed to respond to other dietary and pharmacological
      measures. Antioxidant therapy may be an important advance in the management of
      this type of patient.

PMID- 10199754
TI  - Maltoma of the thyroid in a man with Hashimoto's thyroiditis.
AB  - We report the case of a 42-yr-old man with primary thyroid lymphoma arising from
      mucosa-associated lymphoid tissue (MALT-lymphoma, maltoma). The patient underwent
      a hemithyroidectomy for a growing mass in the right lobe of the thyroid while
      being treated with 1-thyroxine for Hashimoto's thyroiditis. The clinical
      diagnosis of Hashimoto's disease was confirmed by aspiration biopsy of the mass
      during the course of L-thyroxine treatment. Postoperatively, histology showed
      atypical lymphoproliferative infiltrates suspicious of low-grade non-Hodgkin's
      lymphoma of mucosa-associated lymphoid tissue-type, coexisting with a reactive
      process typical of chronic lymphocytic thyroiditis. Immunophenotyping showed a
      mixed B- and T-lymphocyte population, which was nondiagnostic. However, Southern
      blot analysis revealed a clonal rearrangement of the Ig heavy chain gene. This
      case demonstrates that cytology or histology may not distinguish between reactive
      or low-grade lymphomatous thyroid processes. The use of molecular technique was
      essential to prove clonality and the presence of lymphoma.

PMID- 10199755
TI  - Failure of cortisone acetate treatment in congenital adrenal hyperplasia because
      of defective 11beta-hydroxysteroid dehydrogenase reductase activity.
AB  - Congenital adrenal hyperplasia in children is often treated with cortisone
      acetate and fludrocortisone. It is known that certain patients with congenital
      adrenal hyperplasia require very high substitution doses of cortisone acetate,
      and a few patients do not respond to this treatment at all. A patient with 21
      hydroxylase deficiency, for whom elevated pregnanetriol (P3) levels in urine were
      not suppressed during treatment with cortisone acetate (65 mg/m2 x day), was
      examined. The activation of cortisone to cortisol was assessed by measuring
      urinary metabolites of cortisone and cortisol. The patient's inability to respond
      to treatment with cortisone acetate was found to be caused by a low conversion of
      cortisone to cortisol, assumed to be secondary to low 11beta-hydroxysteroid
      dehydrogenase activity (11-oxoreductase deficiency). All exons and exon/intron
      junctions of the 11beta-hydroxysteroid dehydrogenase type1 gene (HSD11L) were
      sequenced without finding any mutations, but a genetic lesion in the promoter or
      other regulatory regions cannot be ruled out. The deficient 11-oxoreductase
      activity seems to have been congenital, in this case, but can possibly be
      attributable to a down-regulation of the enzyme activity. The results support the
      use of hydrocortisone, rather than cortisone acetate, for substitution therapy in
      adrenal insufficiency.

PMID- 10199756
TI  - Increases in bone mineral density after discontinuation of daily human
      parathyroid hormone and gonadotropin-releasing hormone analog administration in
      women with endometriosis.
AB  - Intermittent PTH administration increases spinal bone mineral density (BMD) and
      prevents bone loss from the hip and total body in young women treated with a long
      acting GnRH analog for endometriosis. To establish whether these beneficial
      effects on BMD persist after PTH administration is discontinued, we remeasured
      BMD and biochemical markers of bone turnover in 38 women with endometriosis who
      had been treated with a GnRH analog alone (nafarelin acetate; 200 microg,
      intranasally, twice daily; n = 23; group 1) or who had received nafarelin plus
      human PTH-(1-34) (40 microg/day, s.c.; n = 15; group 2) for 6-12 months 1 yr
      after therapy was completed. Cyclic menstrual function returned promptly after
      nafarelin therapy was discontinued. In group 1, BMD increased significantly at
      all sites [P < 0.001 for the anterior-posterior (AP) and lateral spine; P = 0.014
      for the femoral neck; P = 0.004 for the trochanter], except the proximal radius
      (P = 0.065) and total body bone density (P = 0.069) after nafarelin therapy was
      stopped. In group 2, BMD increased significantly at the AP spine (P < 0.001),
      lateral spine (P = 0.012), femoral neck (P = 0.002), and trochanter (P = 0.029)
      after nafarelin therapy was stopped. BMD of the spine in the AP projection
      increased more in group 2 and than in group 1 after therapy was stopped (P =
      0.045). Despite these increases after discontinuation of nafarelin therapy, BMD
      was still significantly below baseline values at the AP spine (P < 0.001) and
      femoral neck (P = 0.006) and tended to be lower than baseline values at the
      trochanter (P = 0.057) and total body (P = 0.101) at the end of the 1-yr follow
      up period in group 1. In contrast, BMD was significantly above baseline values at
      the AP and lateral spine (P < 0.001) sites and was similar to baseline values at
      the other skeletal sites at the end of the 1-yr follow-up period in group 2. Bone
      turnover returned to baseline values in both groups when therapy was stopped. We
      conclude that the beneficial effects of PTH on bone persist in women who regain
      cyclic menstrual function. Although part of the increases in BMD are probably due
      to restoration of ovarian function, additional increases in BMD most likely
      represent a further anabolic effect of PTH on bone that is not detected until
      after PTH administration is stopped.

PMID- 10199757
TI  - The effects of dose, nutrition, and age on hexarelin-induced anterior pituitary
      hormone secretion in adult patients on maintenance hemodialysis.
AB  - Malnutrition is common in chronic renal failure (CRF) and adversely affects
      prognosis. In view of the anabolic action of GH in CRF, we have studied the
      effects of hexarelin, a GH secretagogue, on CRF. An iv dose-response study in six
      20- to 40-yr-old well nourished hemodialysis (HD) patients was followed by
      administration of the maximally effective dose to six 20- to 40-yr-old healthy
      controls, six 20- to 40-yr-old poorly nourished HD patients, and six 50- to 70-yr
      old poorly nourished HD patients. GH secretion (area under the curve over 180
      min, mean +/- SE) after 2 and 1 microg/kg doses (10.7 +/- 4.2 and 8.2 +/- 5.2
      min/U x L, respectively) was greater than after placebo (0.60 +/- 0.11 min/U x L;
      P < 0.001 and P < 0.05, respectively). The most effective dose (2 microg/kg)
      produced similar GH secretion (11.4 +/- 3.3 min/U x L) in controls. GH secretion
      in the younger poorly nourished HD group (19.0 +/- 4.4 min/U x L) was not
      significantly different from that in the well nourished 20- to 40-yr-old HD
      patients (P = 0.06). GH secretion in the older, poorly nourished HD patients (9.4
      +/- 2.2 min/U x L) was similar to that in the young, poorly nourished group (P =
      0.18). ACTH and cortisol concentrations increased in all groups, whereas PRL
      concentrations were not affected in CRF. The profound action of hexarelin on GH
      secretion has been shown to extend to CRF. Trends were evident toward increasing
      efficacy in malnourished subjects and decreasing efficacy with age. Further
      studies are required to determine whether the acute actions of hexarelin can be
      translated into long term anabolic changes.

PMID- 10199758
TI  - Plasma concentrations of tumor necrosis factor-alpha (TNF-alpha) and soluble TNF
      receptors in patients with anorexia nervosa.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a cytokine with numerous immunological
      and metabolic activities. To study the role of TNF-alpha on the pathophysiology
      of anorexia nervosa and its complications, plasma concentrations of TNF-alpha, 2
      soluble TNF receptors (sTNF-RI and sTNF-RII), and leptin were measured in 20
      female patients with anorexia nervosa (AN) and 20 age-matched normal women (N).
      Plasma TNF-alpha concentrations in AN were significantly higher than those in N
      (4.1 +/- 0.6 pg/mL vs. 1.6 +/- 0.1 pg/mL; P < 0.01). Although no significant
      difference was observed in plasma sTNF-RI concentrations between the two groups,
      plasma sTNF-RII concentrations in AN were significantly higher than those in N
      (2094.0 +/- 138.5 pg/mL vs. 1569.5 +/- 84.0 pg/mL; P < 0.01). Plasma
      concentrations of TNF-alpha and sTNF-RII after treatment of 8 anorectic patients
      were not different from those before treatment, although body fat mass and plasma
      leptin concentrations significantly increased after treatment. Plasma TNF-alpha
      concentrations were not related to body fat mass in anorectic patients. These
      results suggest that the adipose tissue may not be the immediate source of TNF
      alpha in anorectic patients and that TNF-alpha may contribute to the
      pathophysiology of immunological and metabolic abnormalities in anorexia nervosa.

PMID- 10199759
TI  - Success rate of radioiodine therapy in Graves' disease: the influence of
      thyrostatic medication.
AB  - There is controversy whether simultaneous thyrostatic medication influences the
      outcome of radioiodine (131I) therapy in Graves' disease by reducing the absorbed
      energy dose of 131I when delivering a standard dose. We therefore sought to
      ascertain whether the outcome of ablative 131I therapy is in any way affected by
      simultaneous thyrostasis (carbimazole) by aiming for a constant absorbed dose of
      200-250 Gy. We prospectively studied 207 patients with Graves' disease (106 with
      and 101 without simultaneous carbimazole at the time of 131I therapy). All
      patients were reexamined 3, 6, and 12 months after 131I therapy. The 101
      nonthyrostatic patients showed a highly significantly greater success rate (93%)
      than the 106 thyrostatic patients (49%). Stepwise logistic regression
      demonstrated that failure was related to the administration of carbimazole during
      131I therapy (P < 0.00005) and the absorbed dose (P < 0.025), but was not related
      to free T3, free T4, TSH receptor antibodies, or thyroid volume. The success rate
      was 100% in 93 nonthyrostatic patients with absorbed doses of 200 Gy or more, but
      was only 12.5% (1 of 8) for absorbed doses less than 200 Gy. Correlation between
      success and absorbed dose was significantly higher for nonthyrostatic than for
      thyrostatic patients (r = 0.93 vs. r = 0.24). Sixteen patients who discontinued
      thyrostasis 1-3 days before 131I therapy showed 94% successes. Simultaneous
      thyrostasis is the decisive factor against a successful 131I therapy even if the
      significantly reduced 131I uptake/half-life values under thyrostasis are
      compensated with a higher delivered dose to ensure a comparable absorbed dose,
      possibly due to the additionally effective radioprotective properties of
      carbimazole. Therefore, if clinically feasible, we recommend discontinuing
      thyrostasis at least 1 day before beginning 131I therapy, because even in
      hyperthyroid nonthyrostatic patients the success rate was 100%.

PMID- 10199760
TI  - The control on growth hormone release by free fatty acids is maintained in
      acromegaly.
AB  - Free fatty acids (FFA) physiologically regulate GH release via a negative
      feedback. The aim of this study was to examine whether such feedback is preserved
      in acromegaly, a condition in which alterations in other regulatory mechanisms of
      GH release occur. Eight acromegalic patients (group 1: five women and three men,
      43.0 +/- 4.2 yr old, mean +/- SE) received per os on two different days, at a 3
      day-interval, in a random order, placebo or 250 mg of acipimox, an inhibitor of
      lipolysis analogous to nicotinic acid, at 0700 and 1100 h. In both tests GHRH (1
      29 NH2), 50 microg, was administered i.v. at 1300 h. Blood samples for GH, FFA,
      immunoreactive insulin (IRI), and glucose were taken from 0900 to 1500 h, and the
      time period considered for statistical analysis was 1200-1500 h, representative
      of steady-state condition for FFA, IRI, and glucose. Mean plasma FFA levels (1200
      1500 h) were significantly lower after acipimox than after placebo (0.05 +/- 0.01
      vs. 0.17 +/- 0.01 g/L, P < 0.01). In contrast, both mean basal GH levels (1200
      1300 h) and the mean GH response to GHRH (GH delta area, 1300-1500 h) were
      significantly higher after acipimox than after placebo (12.0 +/- 1.9 vs. 7.8 +/-
      1.2 microg/L, P < 0.01; 2937 +/- 959 vs. 1154 +/- 432 microg/L x 120 min, P <
      0.01). The increase in both basal GH levels and GH delta area occurred in all
      eight patients. Acipimox also reduced mean serum IRI (83 +/- 12 vs. 112 +/- 14
      pmol/L) and blood glucose (5.1 +/- 0.1 vs. 5.7 +/- 0.1 mmol/L) levels, as
      compared with placebo (P < 0.03 or less). Eight acromegalic patients (group 2:
      six women and two men, 46.6 +/- 5.7 yr old) underwent a constant i.v. 10% lipid
      infusion (150 mL/h), started at 0900 h and continued until 1500 h. Mean plasma
      FFA levels (1200-1500 h) were significantly higher during lipid infusion than
      after placebo (0.27 +/- 0.01 vs. 0.16 +/- 0.01 g/L, P < 0.02); in contrast, mean
      basal GH levels (1200-1300 h) were reduced by lipid infusion, as compared with
      placebo (9.9 +/- 3.1 vs. 16.6 +/- 4.4 microg/L, P < 0.01), and the same occurred
      for the GH delta area after GHRH (2498 +/- 1643 vs. 4512 +/- 1988 microg/L x 120
      min, P < 0.01). Serum IRI and blood glucose levels were similar after placebo and
      during lipid infusion. These data indicate that, in acromegaly, the acute
      reduction of circulating FFA levels results in increased GH release, whereas the
      increase in circulating FFA levels is accompanied by a reduced GH release. Taken
      together, these findings suggest that, in acromegaly, the control of FFA on GH
      release is preserved.

PMID- 10199761
TI  - Immunoglobulin G insulin autoantibodies in BABYDIAB offspring appear postnatally:
      sensitive early detection using a protein A/G-based radiobinding assay.
AB  - Insulin autoantibodies (IAA) are early sensitive markers of pre-diabetes in the
      young. The aim of this study was to assess whether, using IgG-specific
      measurement with a protein A/G assay, IAA are already present at birth, and
      whether this assay is suitable for early autoantibody screening. Cord blood and
      follow-up samples from offspring of parents with type 1 diabetes included in the
      BABYDIAB study were analyzed. Although insulin antibodies in cord blood from
      children of mothers with type 1 diabetes were readily detected and correlated
      well with levels in the maternal circulation, no insulin binding was detected in
      247 cord blood samples from children of father probands. IgG IAA were detected at
      2 yr in all 21 children who had multiple islet autoantibodies or who later
      developed type 1 diabetes, but were confirmed in only 6 of 58 with IAA by the
      conventional IAA assay in the absence of other islet autoantibodies. False
      positive IAAs in the conventional assay were often attributable to hemolysis.
      Hemolysis did not affect protein A/G IAA measurement, and results in whole
      capillary blood samples were comparable to those in corresponding serum samples
      (r2 = 0.99). These data show that IgG IAA appear early and after birth, and that
      the protein A/G IAA assay is sufficiently sensitive for early screening. The
      specificity of this assay requires further evaluation.

PMID- 10199762
TI  - Clinical trial of transdermal testosterone and oral levonorgestrel for male
      contraception.
AB  - Approaches to hormonal male contraception are predominantly based on injectable
      testosterone (T) application. As most users would prefer an injection-independent
      modality, this study was designed to develop a self-applicable hormonal male
      contraceptive regimen by combining transdermal T with an oral gestagen. Eleven
      healthy men (23-40 yr old) were treated with oral levonorgestrel and transdermal
      T for 24 weeks. T was applied daily as a transdermal patch to be worn on the
      trunk. Levonorgestrel was taken orally at a dose of 250 microg daily up to week
      12, followed by 500 microg to week 24 in those volunteers who had not become
      azoospermic by that time. Within 24 weeks, 2 of 11 volunteers had become
      azoospermic, and 3 of 11 showed sperm concentrations below 3 million/mL. The
      sperm concentrations of the remaining volunteers declined, but failed to reach
      the limit considered compatible with contraception by WHO. Treatment resulted in
      suppression of LH, FSH, and sex hormone-binding globulin, whereby the volunteers
      with lower sperm concentrations showed more pronounced suppression than the
      others. Mean T concentrations remained within the lower limit of normal and on
      occasions were below this level. There were no complaints of hypoandrogenism.
      Although mean levels of low density lipoprotein cholesterol, apolipoprotein B, as
      well as basal and postprandial insulin increased, high density lipoprotein
      cholesterol and apolipoprotein A-I decreased during the treatment phase. Changes
      in lipid parameters were normalized within 3 weeks after cessation of medication.
      Although only 5 of 11 volunteers reached the target sperm counts (<3 million/mL),
      the study shows that a self-applicable hormonal male contraceptive could be
      developed.

PMID- 10199763
TI  - Spironolactone, but not flutamide, administration prevents bone loss in
      hyperandrogenic women treated with gonadotropin-releasing hormone agonist.
AB  - GnRH agonists (GnRHa) have recently been proposed for the treatment of hirsutism
      in women with the polycystic ovary syndrome (PCOS). As most of these subjects
      have increased androgen secretion from both ovaries and adrenal glands, the
      association of GnRHa with antiandrogen drugs might enhance the clinical response
      to treatment. On the other hand, this association might also potentiate the
      adverse effects of GnRHa on bone metabolism, generating a potentially harmful
      situation at the skeletal level. In this study we investigated in 41 PCOS
      patients the skeletal effects of a 6-month course of GnRHa (tryptorelin, 3.75 mg,
      i.m., monthly), either alone (n = 12) or associated with the antiandrogen drugs
      spironolactone (100 mg, orally, once daily; n = 14) or flutamide (250 mg, once
      daily; n = 15). In all subjects bone mineral density was measured before and
      after treatment by dual energy x-ray absorptiometry at the lumbar spine (L2-L4)
      and at the femoral neck and Ward's triangle. In addition, at baseline and after 6
      months of therapy, bone metabolism markers (serum and urinary calcium, serum
      phosphorus and alkaline phosphatase, plasma osteocalcin, and urinary
      hydroxyproline) and endocrine parameters (serum gonadotropins, estradiol, and
      free testosterone) were assayed. Women given either GnRHa alone or associated
      with spironolactone or flutamide were similar for age and body mass index. At
      baseline, the 3 groups of PCOS women were also similar for endocrine and bone
      parameters. After 6 months, all treatments determined similar striking
      suppressions of serum gonadotropins and sex steroids. Concurrently, bone mineral
      density was significantly reduced at all examined sites in subjects receiving
      either GnRHa alone or GnRHa plus flutamide. Conversely, women given GnRHa plus
      spironolactone did not show any change in skeletal mass from baseline values (P <
      0.05-0.01 among groups). Biochemical parameters of bone metabolism were
      consistent with densitometric assessments. In conclusion, after a 6-month course
      of therapy, bone mineral density is reduced in PCOS women given either GnRHa
      alone or GnRHa plus flutamide, but not in those receiving GnRHa plus
      spironolactone. The mechanisms of the bone-sparing effect of spironolactone
      remain to be determined. Nevertheless, this drug could represent a useful tool to
      prevent skeletal loss in women given GnRHa as well as in other hypoestrogenic
      conditions, in particular when estrogens are not recommended.

PMID- 10199764
TI  - Serum antibodies against the flavoprotein subunit of succinate dehydrogenase are
      sensitive markers of eye muscle autoimmunity in patients with Graves'
      hyperthyroidism.
AB  - Thyroid-associated ophthalmopathy is an autoimmune disorder of the extraocular
      muscles and orbital connective tissue, which is usually associated with Graves'
      hyperthyroidism. Well-studied markers of ophthalmopathy are eye muscle membrane
      antigens, reportedly of approximately 64-kDa molecular mass. One, originally
      identified only as the 64-kDa protein, has recently been shown to be the
      flavoprotein (Fp) subunit of mitochondrial succinate dehydrogenase, which has a
      correct molecular mass of 67 kDa. We have used purified beef heart Fp as antigen
      in an enzyme-linked immunosorbent assay for cross-reactive human autoantibodies.
      Sera have been screened from patients with thyroid-associated ophthalmopathy
      classified according to activity and presence or not of eye muscle disease, and
      from those with Graves' hyperthyroidism without eye involvement. Also examined
      were serum samples taken periodically from 20 patients with Graves'
      hyperthyroidism during 24 months of treatment of their hyperthyroidism with
      antithyroid drugs. Four of these patients had ophthalmopathy at the onset, 12
      developed ophthalmopathy, and 4 did not develop any eye signs during treatment.
      Anti-Fp subunit antibodies were detected in 73% of patients with active
      ophthalmopathy and evidence of eye muscle involvement but only in 25% if there
      was only congestive ophthalmopathy. These values were 0% and 11% for patients
      with chronic ophthalmopathy, with or without eye muscle dysfunction,
      respectively. The antibodies were also detected in 14% of patients with Graves'
      hyperthyroidism without evident ophthalmopathy, 11% of patients with
      nonimmunologic thyroid disorders, 12% of type I diabetics, and 12% of age- and
      sex-matched normal subjects. Significantly, appearance of anti-Fp antibodies
      predicted the development of ophthalmopathy in 5 of the 6 patients with Graves'
      hyperthyroidism, who developed eye muscle dysfunction after treatment of the
      hyperthyroidism, and coincided with the onset of eye muscle signs in the other
      patient. Antibodies were not detected in any of 6 patients who developed
      congestive ophthalmopathy without evidence of eye muscle damage or in 4 patients
      who did not develop any eye signs. In conclusion, we have shown a close
      relationship between eye muscle disease and serum antibodies against the Fp
      subunit of succinate dehydrogenase in patients with Graves' hyperthyroidism.

PMID- 10199765
TI  - The autonomic control of heart rate and insulin resistance in young adults.
AB  - The pathophysiology of insulin resistance is unclear. A link between increased
      heart rate (HR) and insulin resistance suggests an association with sympathetic
      nervous system activity. To further evaluate this, we examined autonomic activity
      using spectral analysis of HR variability (HRV), which provides a measure of
      cardiac sympathovagal modulation, and related this to insulin sensitivity (Si) in
      137 men and women (20 yr old). The HRV spectrum displays 2 major peaks: a high
      frequency peak, reflecting vagal activity, and a low-frequency peak caused by
      vagal and sympathetic activity. The high-to-low ratio (HLratio) reflects
      sympathovagal balance. Si was measured, using the i.v. glucose tolerance test
      with minimal modeling, and HR data was derived from a 15-min supine
      electrocardiogram. Women were more insulin resistant than men (Si, 3.94 vs. 5.09
      10(4) min(-1)/per pmol x L; P = 0.002), had higher HR (59 vs. 56 beats/min, P =
      0.019), but had a higher HLratio (2.04 vs. 1.31, P = 0.001). In men (but not
      women), Si correlated with HR (r = -0.410, P = 0.001) and measures of HRV:
      HLratio (r = 0.291, P = 0.002) independently of body mass index. In conclusion,
      Si correlates with cardiac sympathovagal balance in men, but not women,
      suggesting gender differences in the autonomic modulation of insulin resistance.

PMID- 10199766
TI  - Effects of pharmacological doses of nandrolone decanoate and progressive
      resistance training in immunodeficient patients infected with human
      immunodeficiency virus.
AB  - This nonplacebo-controlled, open label, randomized study was conducted to test
      the hypotheses that pharmacological doses of nandrolone decanoate would increase
      lean body tissue, muscle mass, and strength in immunodeficient human
      immunodeficiency virus-infected men, and that these effects would be enhanced
      with progressive resistance training (PRT). Thirty human immunodeficiency virus
      positive men with fewer than 400 CD4 lymphocytes/mm3 were randomly assigned to
      receive weekly injections of nandrolone alone or in combination with supervised
      PRT at 80% of the one-repetition maximum three times weekly for 12 weeks. Total
      body weight increased significantly in both groups (3.2 +/- 2.7 and 4.0 +/- 2.0
      kg, respectively; P < 0.001), with increases due primarily to augmentation of
      lean tissue. Lean body mass determined by dual energy x-ray absorptiometry
      increased significantly more in the PRT group (3.9 +/- 2.3 vs. 5.2 +/- 5.7 kg,
      respectively; P = 0.03). Body cell mass by bioelectrical impedance analysis
      increased significantly (P < 0.001) in both groups (2.6 +/- 1.0 vs. 2.9 +/- 0.8
      kg), but to a similar magnitude (P = NS). Significant increases in cross
      sectional area by magnetic resonance imaging of total thigh muscles (1538 +/- 767
      and 1480 +/- 532 mm2), quadriceps (705 +/- 365 and 717 +/- 288 mm2), and
      hamstrings (842 +/- 409 and 771 +/- 295 mm2) occurred with both treatment
      strategies (P < 0.001 for the three muscle areas); these increases were similar
      in both groups (P = NS). By the one-repetition method, strength increased in both
      upper and lower body exercises, with gains ranging from 10.3-31% in the
      nandrolone group and from 14.4-53.0% in the PRT group (P < 0.006 with one
      exception). Gains in strength were of significantly greater magnitude in the PRT
      group (P < or = 0.005 for all comparisons), even after correction for lean body
      mass. Thus, pharmacological doses of nandrolone decanoate yielded significant
      gains in total weight, lean body mass, body cell mass, muscle size, and strength.
      The increases in lean body mass and muscular strength were significantly
      augmented with PRT.

PMID- 10199767
TI  - The growth hormone (GH) response to the arginine plus GH-releasing hormone test
      is correlated to the severity of lipid profile abnormalities in adult patients
      with GH deficiency.
AB  - The aim of the present study was to correlate the degree of the GH response to
      the combined arginine and GHRH (ARG+GHRH) test with clinical status in 157 adult
      hypopituitary patients and 35 healthy controls. On the basis of the GH response
      to ARG+GHRH, the 192 subjects were subdivided into 5 groups: group 1, very severe
      GH deficiency (GHD; 65 patients with GH peak <3 microg/L); group 2, severe GHD
      (37 patients with GH peak between 3.1-9 microg/L); group 3, partial GHD (25
      patients with GH peak between 9.1-16.5 microg/L); group 4, non-GHD (30 patients
      with GH peak >16.5 microg/L); and group 5 (35 controls with GH peak >16.5
      microg/L). Plasma insulin-like growth factor I (IGF-I) concentrations were lower
      (P < 0.001) in patients of group 1 (74.4 +/- 6.7 microg/L) and group 2 (81.4 +/-
      6.8 microg/L) than in those of group 3, 4, and 5 (163.6 +/- 40.6, 185.9 +/- 21,
      and 188.8 +/- 11.1 microg/L, respectively). Plasma IGF-binding protein-3
      concentrations were lower (P < 0.01) in group 1 (2.1 +/- 0.2 mg/L) and group 2
      (2.0 +/- 0.2 mg/L) than in group 3 (3.4 +/- 0.7 mg/L) and group 5 (3.8 +/- 0.2
      mg/L). In patients of group 1, total cholesterol (228.3 +/- 5.7 mg/dL) and
      triglycerides levels (187.4 +/- 15.3 mg/dL) were higher than those in group 3
      (196.6 +/- 9.6 and 115.8 +/- 10.1 mg/dL, respectively), group 4 (176.8 +/- 11.3
      and 101.4 +/- 12.5 mg/dL, respectively), and group 5 (160 +/- 6.9 and 99.3 +/-
      5.4 mg/dL, respectively). High density lipoprotein cholesterol levels were lower
      in patients of group 1 (45.2 +/- 2.4 mg/dL) than in those of group 4 (54.7 +/-
      3.5 mg/dL; P < 0.05) and group 5 (53.6 +/- 2 mg/dL; P < 0.001), whereas low
      density lipoprotein cholesterol levels were higher in patients of group 1 (127.3
      +/- 7.9 mg/dL), group 2 (129.2 +/- 9.5 mg/dL), and 3 (133 +/- 9 mg/dL) than in
      those of group 5 (102.4 +/- 7.4 mg/dL; P < 0.05). Patients of group 2 had total
      cholesterol, high density lipoprotein cholesterol, and triglycerides levels at an
      intermediate level with respect to those in groups 1, 3, and 4. Among the five
      groups, no difference was found in fasting glucose concentrations, heart rate, or
      systolic and diastolic blood pressures. A significant increase in fat body mass
      and a decrease in lean body mass and total body water were found in all patients
      compared to controls. Disease duration was significantly shorter in patients of
      group 4 than in those of the remaining three groups (P < 0.001). A significant
      correlation was found between the GH peak after ARG+GHRH and disease duration (r
      = -0.401; P < 0.001), plasma IGF-I (r = 0.434; P < 0.001), total cholesterol (r =
      -0.324; P < 0.001), and triglycerides levels (r = -0.219; P < 0.05). A
      significant multiple linear regression coefficient was found between the GH peak
      after ARG+GHRH and plasma IGF-I levels (t = 2.947; P < 0.005), total cholesterol
      levels (t = -2.746; P < 0.01), and disease duration (t = -2.397; P < 0.05). In
      conclusion, the results of the present study indicate that the degree of the GH
      response to ARG+GHRH is correlated with the severity of lipid profile
      abnormalities and substantiate the reliability of the ARG+GHRH test for the
      diagnosis of GHD in adults. Because at present GH treatment is recommended only
      in adult patients with severe GHD, patients with a GH response below 9 microg/L
      to the ARG+GHRH test should be treated with GH, as should patients with a peak GH
      response to an insulin tolerance test below 3 microg/L.

PMID- 10199768
TI  - Insulin-like growth factor binding proteins (IGFBPs) and IGFBP-related protein 1
      levels in cerebrospinal fluid of children with acute lymphoblastic leukemia.
AB  - Abnormalities in insulin-like growth factor binding proteins (IGFBPs) have been
      reported in the cerebrospinal fluid (CSF) of children with acute leukemia. In the
      present study, we have further characterized the IGFBPs in whole CSF
      prospectively in 11 children with acute B-lineage lymphoblastic leukemia (ALL)
      undergoing chemotherapy. Western ligand blots Western immunoblots using a new
      anti-IGFBP-6 and a new IGFBP-rP1 (related protein-1 antibody and immunoassays
      (Diagnostic Systems Laboratories, Inc., Webster, TX) were used to characterize
      and measure IGFBP-6, IGFBP-2, IGFBP-3, and IGFBP-rP1 in children with ALL at
      diagnosis, and with treatment. Comparisons at baseline were made with 11 children
      with meningitis and 11 children with febrile convulsions (controls). The mean (+/
      SE) CSF IGFBP-6 in ALL patients, 56 (+/- 7) ng/mL, was significantly lower than
      in meningitis, 97 (+/- 17) ng/mL; and in controls, 123 (+/- 24) ng/mL (P < 0.05,
      t test). In contrast, CSF IGFBP-3 was elevated in ALL patients, 29 (+/- 9) ng/mL;
      compared with meningitis, 11 (+/- 1) ng/mL; and controls, 10 (+/- 1) ng/mL (P <
      0.05, t test); and IGFBP-2 did not differ among the three groups (47-59 ng/mL, P
      > 0.05). CSF IGFBP-6 remained very low in the patients with ALL, at 4 and 36
      weeks of treatment; whereas IGFBP-3 decreased to control levels, and IGFBP-2 did
      not change significantly. At baseline, Western ligand blots and Western
      immunoblots identified a 25- to 28-kDa broad band as IGFBP-6 and a 30-kDa band as
      IGFBP-2 and showed that there was almost no intact IGFBP-3 in CSF. IGFBP-rP1 was
      also present in the CSF and was elevated in patients with ALL, compared with the
      2 control groups. In conclusion, at diagnosis, IGFBP-rP1 and fragments of IGFBP-3
      are elevated, and IGFBP-6 is significantly decreased, in the CSF of ALL children;
      and IGFBP-6 remained low, with treatment, up to 36 weeks. The role of the IGFBPs
      and IGFBP-rPs in central nervous system acute leukemia remain to be further
      elucidated.

PMID- 10199769
TI  - Serum leptin response to the acute and chronic administration of growth hormone
      (GH) to elderly subjects with GH deficiency.
AB  - In human studies, the principal determinant of serum leptin concentrations is fat
      mass (FM), but lean mass (LM) also has a significant negative influence. GH
      treatment in GH deficiency (GHD) alters body composition, increasing LM and
      decreasing FM, and thus would be expected to alter leptin concentrations. We have
      therefore examined the acute and chronic effects of GH on serum leptin in 12
      elderly GHD subjects (ages 62-85 yr; 3 women and 9 men). FM (kilograms) and LM
      (kilograms) were determined by dual energy x-ray absortiometry. Leptin, insulin,
      insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein-1 (IGFBP-1),
      IGFBP-2, and IGFBP-3 were measured by specific immunoassays. Leptin, insulin, and
      IGFBP-1 concentrations were log10 transformed, and data were expressed as the
      geometric mean (-1, +1 tolerance factor). All other data are presented as the
      mean +/- SD. In the acute study, patients received a single bolus dose of GH (0.1
      mg/kg BW) at time zero, with blood samples drawn at 0, 12, 24, 48, and 72 h and 1
      and 2 weeks. There was a significant rise in leptin, insulin, and IGF-I at a
      median time of 24 h, followed by a significant fall, and nadir concentrations
      were reached at a median time of 1.5 weeks (leptin) or 2 weeks (insulin and IGF
      I). IGFBP-3 concentrations were also significantly increased, but peak
      concentrations were not achieved until 48 h. IGF-II, IGFBP-1, and IGFBP-2
      exhibited transient decreases before returning to baseline levels. There was no
      relationship between increased leptin concentrations and either insulin or IGF-I
      concentrations. In the chronic study, patients received daily GH treatment at
      doses of 0.17, 0.33, and 0.5 mg/day, each for 3 months (total time on GH, 9
      months), and were then followed off GH for a further 3 months. Dual energy x-ray
      absortiometry was undertaken at 0, 3, 6, 9, and 12 months, and blood samples were
      drawn at these time points. Over 9 months on GH there was a significant fall in
      FM and a significant rise in LM, but no change in leptin. There were also
      significant increments in insulin, IGF-I, and IGFBP-3, whereas IGF-II, IGFBP-1,
      and IGFBP-2 did not change over 9 months of GH treatment. After 3 months off GH,
      there was a significant rise in FM and leptin. High dose single bolus GH led to
      an increase in serum leptin within 24 h apparently independent of changes in
      insulin or IGF-I. Despite the changes in body composition during chronic GH
      treatment, there was no change in leptin. However, discontinuation of GH led to a
      rapid reversal of the favorable body composition and a rise in serum leptin.

PMID- 10199770
TI  - Growth hormone (GH) therapy in GH-deficient adults influences the response to a
      dietary load of cholesterol and saturated fat in terms of cholesterol synthesis,
      but not serum low density lipoprotein cholesterol levels.
AB  - An increased dietary load of cholesterol (ch) and saturated fat increases serum
      low density lipoprotein ch (LDL-ch) levels. GH therapy in GH-deficient adults
      decreases serum LDL-ch levels. In the rat, GH is important for resistance to
      dietary cholesterol in terms of serum cholesterol levels. The aim of this study
      was to investigate the influence of GH on the effects of an increase in the
      intake of cholesterol and saturated fat on serum lipoproteins and markers for
      cholesterol synthesis in man. Six GH-deficient adults were given an isocaloric
      diet enriched in cholesterol and saturated fat for 17 days with and without GH
      therapy (1-1.5 U/day). Serum cholesterol, LDL-ch, apolipoprotein B (apoB), and
      apoA1 levels increased during the diet period with GH therapy and tended to
      increase during the diet period without GH. However, GH therapy did not influence
      the dietary effect on serum cholesterol, LDL-ch, apoA1, or apoB levels. Serum
      levels of triglycerides, very low density lipoprotein ch, high density
      lipoprotein ch, and apoE were not affected by diet or GH therapy. GH therapy
      increased serum lipoprotein(a) levels, but did not affect the response to diet.
      The serum total delta7-lathosterol/cholesterol ratio increased less during the
      diet period with GH therapy than during the diet period without GH. Serum 7alpha
      hydroxy-4-cholesten-3-one levels tended to increase during both diet periods, but
      were not influenced by GH treatment. Serum plant sterol levels did not change.
      These results indicate that GH counteracts an increase in cholesterol synthesis
      induced by a high fat diet without affecting bile acid synthesis or sterol
      absorption. GH therapy did not have any major influence on the dietary effects on
      serum lipoprotein levels.

PMID- 10199771
TI  - A prospective randomized trial comparing low dose flutamide, finasteride,
      ketoconazole, and cyproterone acetate-estrogen regimens in the treatment of
      hirsutism.
AB  - Sixty-six hirsute women were randomized and treated with 1) flutamide (n = 15),
      250 mg/day; 2) finasteride (n = 15), 5 mg/day; 3) ketoconazole (n = 16), 300
      mg/day; and 4) ethinyl estradiol (EE)-cyproterone acetate (CPA; n = 20), 0.01 mg
      EE/day for the first week, 0.02 mg EE/day for the second week, and 0.01 mg EE/day
      for the third week, followed by a pause of 7 days, then 12.5 mg CPA/day added
      during the first 10 days of every month for 12 months. Hirsutism was evaluated by
      the Ferriman-Gallwey score, and hair diameter and hair growth rate were
      determined by a special image analysis processor in basal conditions and after
      90, 180, 270, and 360 days of treatment. All treatments produced a significant
      decrease in the hirsutism score, hair diameter, and daily hair growth rate:
      flutamide, -55 +/- 13%, -21 +/- 14%, and -37 +/- 18%; finasteride, -44 +/- 13%, 
      16 +/- 12%, and -27 +/- 14%; ketoconazole, -53 +/- 18%, -14 +/- 12%, and -30 +/-
      21%; and EE-CPA, -60 +/- 18%, -20 +/- 11%, and -28 +/- 21%. Some differences
      existed among treatments with regard to effectiveness; EE-CPA and flutamide seem
      to be the most efficacious in improving hirsutism. For the hirsutism score, a
      greater decrease was seen with EE-CPA (-60 +/- 18%) than with finasteride (-44 +/
      13%; P < 0.01) and a greater decrease was seen with flutamide (-58 +/- 18%) than
      with finasteride (-44 +/- 13%; P < 0.05). Flutamide is the fastest in decreasing
      hair diameter; EE-CPA is the fastest in slowing down hair growth, even though at
      the end of the treatment there was a significant difference between flutamide and
      finasteride only (-41 +/- 18% vs. -27 +/- 14%; P < 0.05). Flutamide,
      ketoconazole, and EE-CPA induced a significant decrease in total and free
      testosterone, 5alpha-dihydrotestosterone, dehydroepiandrosterone,
      dehydroepiandrosterone sulfate, and androstenedione plasma levels. During the EE
      CPA treatment, gonadotropins were suppressed, and the sex hormone-binding
      globulin level increased. Finasteride induced a decrease in
      dehydroepiandrosterone sulfate and 5alpha-dihydrotestosterone and an increase in
      testosterone levels. Very few side-effects were observed during treatment with
      low doses of flutamide, EE-CPA, and particularly finasteride. Flutamide induced a
      decrease whereas EE-CPA induced an increase in triglycerides and cholesterol,
      showing higher values within the normal range. Ketoconazole induced several side
      effects and complications, and several people dropped out of the study. Despite
      different modalities of action and significantly different effects on androgen
      levels, low doses of flutamide, finasteride, and EE-CPA constitute very
      satisfactory alternative therapeutic regimens in the treatment of hirsutism.

PMID- 10199772
TI  - Reactivation of pituitary hormone release and metabolic improvement by infusion
      of growth hormone-releasing peptide and thyrotropin-releasing hormone in patients
      with protracted critical illness.
AB  - Protracted critical illness is marked by protein wasting resistant to feeding, by
      accumulation of fat stores, and by suppressed pulsatile release of GH and TSH. We
      previously showed that the latter can be reactivated by brief infusion of GH
      releasing peptide (GHRP-2) and TRH. Here, we studied combined GHRP-2 and TRH
      infusion for 5 days, which allowed a limited evaluation of the metabolic
      effectiveness of this novel trophic endocrine strategy. Fourteen patients (mean
      +/- SD age, 68 +/- 11 yr), critically ill for 40 +/- 28 days, were compared to a
      matched group of community-living control subjects at baseline and subsequently
      received 5 days of placebo and 5 days of GHRP-2 plus TRH (1 + 1 microg/kg x h)
      infusion in random order. At baseline, impaired anabolism, as indicated by
      biochemical markers (osteocalcin and leptin), was linked to hyposomatotropism
      [reduced pulsatile GH secretion, as determined by deconvolution analysis, and low
      GH-dependent insulin-like growth factor and binding protein (IGFBP) levels].
      Biochemical markers of accelerated catabolism (increased protein degradation and
      bone resorption) were related to tertiary hypothyroidism and the serum
      concentration of IGFBP-1, but not to hyposomatotropism. Metabolic markers were
      independent of elevated serum cortisol. After 5 days of GHRP-2 plus TRH infusion,
      osteocalcin concentrations increased 19% vs. -6% with placebo, and leptin had
      rose 32% vs. -15% with placebo. These anabolic effects were linked to increased
      IGF-I and GH-dependent IGFBP, which reached near-normal levels from day 2 onward.
      In addition, protein degradation was reduced, as indicated by a drop in the
      urea/creatinine ratio, an effect that was related to the correction of tertiary
      hypothyroidism, with near-normal thyroid hormone levels reached and maintained
      from day 2 onward. Concomitantly, a spontaneous tendency of IGFBP-1 to rise and
      of insulin to decrease was reversed. Cortisol concentrations were not detectably
      altered. In conclusion, 5-day infusion of GHRP-2 plus TRH in protracted critical
      illness reactivates blunted GH and TSH secretion, with preserved pulsatility,
      peripheral responsiveness, and feedback inhibition and without affecting serum
      cortisol, and induces a shift toward anabolic metabolism. This provides the first
      evidence of the metabolic effectiveness of short term GHRP-2 plus TRH agonism in
      this particular wasting condition.

PMID- 10199773
TI  - Growth hormone (GH) deficiency (GHD) of childhood onset: reassessment of GH
      status and evaluation of the predictive criteria for permanent GHD in young
      adults.
AB  - GH secretion was reevaluated after completion of GH treatment at a mean age of
      19.2 +/- 3.2 yr in 35 young adults with childhood-onset GH deficiency (GHD). The
      patients were subdivided into 4 groups according to their first pituitary
      magnetic resonance imaging (MRI) findings: group I, 11 patients with isolated GHD
      (IGHD) and normal pituitary volume (280 +/- 59.4 mm3); group II, 7 patients with
      IGHD and small pituitary gland (163.1 +/- 24.4 mm3; P = 0.0009 vs. group I);
      group III, 13 patients (5 with IGHD and 8 with multiple pituitary hormone
      deficiency) with congenital hypothalamic-pituitary abnormalities such as
      pituitary hypoplasia (95.8 +/- 39.3 mm3; P < 0.00001 vs. group I and P = 0.003
      vs. group II), pituitary stalk agenesis, and posterior pituitary ectopia; and
      group IV, 4 patients with multiple pituitary hormone deficiency secondary to
      craniopharyngioma. Pituitary MRI and GH secretory status were reevaluated after
      GH withdrawal using arginine, insulin induced-hypoglycemia, and sequential
      arginine-insulin tests. Serum insulin-like growth factor I (IGF-I) and IGF
      binding protein-3 (IGFBP-3) were determined at the time of retesting and 6, 12,
      and 24 months after discontinuation of treatment in the patients with permanent
      GHD and after 6 months in those with normal GH responses to stimulation. The
      patients in groups I and II showed a normal response to stimulation after
      completion of GH treatment regardless of pituitary size, whereas all patients in
      groups III and IV still had a GH response of less than 3 microg/L to any of the
      tests. Pituitary volume normalized in 6 of 7 patients in group II, whereas in all
      patients in group III MRI studies confirmed the initial findings. Mean IGF-I and
      IGFBP-3 concentrations at the time of retesting were significantly higher in
      groups I and II than in groups III and IV. In patients of groups III and IV, mean
      IGF-I was significantly decreased after 6 and 12 months, whereas IGFBP-3 was
      significantly decreased 12 months after treatment withdrawal. Our results confirm
      that a high proportion of children with IGHD and normal or small pituitary show
      normalization of GH secretion at the completion of GH treatment, whereas GHD is
      permanent in all patients with pituitary hypoplasia, pituitary stalk agenesis,
      and posterior pituitary ectopia. IGF-I and IGFBP-3 determinations shortly after
      GH withdrawal had limited value in the diagnosis of GHD of childhood onset
      associated with congenital hypothalamic-pituitary abnormalities, but became
      accurate after 6-12 months. We suggest that patients with GHD and congenital
      hypothalamic-pituitary abnormalities do not require further investigation of GH
      secretion, whereas patients with IGHD and normal or small pituitary gland should
      be retested well before the attainment of adult height.

PMID- 10199774
TI  - Decrease in carotid intima-media thickness after one year growth hormone (GH)
      treatment in adults with GH deficiency.
AB  - An increased carotid arterial intima-media thickness (IMT) has been reported in
      hypopituitary adults untreated for GH deficiency. In the present study, the
      effect of GH replacement on IMT and cardiovascular risk factors was prospectively
      investigated, in GH deficiency patients treated at a mean dose of 1 UI/day during
      1 yr (n = 22) and 2 yr (n = 11). The IMT measurements were performed by the same
      experienced physician, and the coefficient of variation (calculated in two
      control groups) was below 6.5%. IMT at baseline was related to conventional risk
      factors. After 1 yr GH treatment, IMT decreased from 0.78 +/- 0.03 mm to 0.70 +/-
      0.03 mm (P < 0.001). The decrement was observed in 21 of 22 patients. After 2 yr
      GH treatment, IMT had stabilized at 0.70 +/- 0.04 mm and remained significantly
      different from baseline values (P < 0.003). GH treatment resulted in a moderate
      decrease in waist circumference and body fat mass and an increase in VO2 max.
      Conventional cardiovascular risk factors were unmodified except for a transient
      10% decrease in low-density lipoprotein cholesterol at 6 months. The contrast
      between the limited metabolic effect of treatment and the importance and
      precocity of the changes in IMT suggests that the decrease in IMT was not
      exclusively attributable to a reversal in the atherosclerotic process. A direct
      parietal effect of GH replacement on the arterial wall might also be involved.
      The consequences, in terms of cardiovascular risk, should be established by
      randomized prospective trials.

PMID- 10199775
TI  - Luteinizing hormone and different genetic variants, as indicators of frailty in
      healthy elderly men.
AB  - We investigated the possible clinical correlates between the serum LH
      concentration and characteristics of frailty and determined the presence and
      concentration of a genetic LH variant in an independently living population of
      elderly men. After exclusion of subjects with severe mobility problems and signs
      of dementia, 403 healthy men (aged 73-94 yr) were randomly selected from a
      population-based sample. Total testosterone (T), sex hormone-binding globulin
      (SHBG), and leptin were determined by RIA. Non-SHBG-bound T was calculated. LH
      and the presence of the genetic LH variant were measured using immunofluorometric
      assays. The characteristics of frailty were leg extensor strength using
      dynamometry, bone mineral density of total body and proximal femur, and body
      composition, including lean mass and fat mass, measured by dual energy x-ray
      absorptiometry. Disability was further assessed by the Modified Health Assessment
      Questionnaire and by a measure of physical performance. LH significantly
      increased with age and inversely correlated with T and non-SHBG-bound T. LH was
      inversely related to muscle strength and lean mass, and both relations were
      independent of T. LH was positively related to self-reported disability (Modified
      Health Assessment Questionnaire); 12.5% of the study population was heterozygous
      for the LH variant allele. T levels and the degree of frailty were not different
      in the wild-type LH group compared with the heterozygote LH variant group. A
      significant positive relation between LH and fat mass as well as leptin was only
      present in the heterozygote LH variant group. In conclusion, serum LH levels
      increases with age in independently living elderly men and correlates inversely
      with a variety of indicators of frailty. The observed relation between LH and
      frailty, independent of T, suggests that LH reflects serum androgen activity in a
      different way than T, possibly reflecting more closely the combined feedback
      effect of estrogen and androgen. A difference in biological response between the
      two LH forms is suggested, as a difference exists in the relation between LH and
      fat mass, respectively, and leptin in the heterozygote LH variant subjects vs.
      the wild-type LH subjects.

PMID- 10199776
TI  - 17Beta-hydroxysteroid dehydrogenase type 1, 2, 3, and 4 expression and enzyme
      activity in human anterior pituitary adenomas.
AB  - 17Beta-hydroxysteroid dehydrogenase (17betaHSD) isoforms reversibly catalyze the
      final step in the formation of estradiol (E2) from estrone (E1) and the formation
      of testosterone from androstenedione. We have investigated 17betaHSD type 1, 2,
      3, and 4 gene expression and 17betaHSD estrogenic activity in human anterior
      pituitary adenomas. 17BetaHSD messenger ribonucleic acid (mRNA) expression was
      studied by RT-PCR in 42 pituitary tumors and 3 normal pituitaries, 17betaHSD
      activity was studied in 11 tumors and 17betaHSD type 1 was immunolocalized in
      vitro in 6 tumors. 17BetaHSD type 1 gene expression was detected in 34 of 42
      adenomas in all tumor subtypes; 17betaHSD type 2 mRNA was detected in 18 of 42
      adenomas, but not in prolactinomas; 17betaHSD type 3 mRNA was detected in 12 of
      42 adenomas, but not in corticotropinomas; 17betaHSD type 4 was expressed in 20
      of 42 adenomas by all adenoma subtypes. Reversible 17betaHSD activity was found
      in 9 of 11 adenomas, and 17betaHSD type 1 immunopositivity was cytoplasmically
      distributed in all 6 adenomas in vitro. All 4 17betaHSD isoforms are variably
      expressed in human anterior pituitary adenomas, which also show 17betaHSD enzyme
      activity, suggesting that 17betaHSD may play an important role in regulating the
      local cellular levels of estradiol.

PMID- 10199777
TI  - Low serum levels of free and total insulin-like growth factor I (IGF-I) in
      patients with anorexia nervosa are not associated with increased IGF-binding
      protein-3 proteolysis.
AB  - Patients with anorexia nervosa (AN) are GH resistant, with elevated GH levels and
      low serum levels of total insulin-like growth factor I (IGF-I). IGF-I action is
      modulated by IGF-binding proteins (IGFBPs), and a variety of catabolic states has
      been characterized by the presence of increased IGFBP-3 proteolysis. The present
      study was performed to examine the levels of free IGFs in AN and to clarify
      whether AN is associated with increased IGFBP-3 proteolytic activity. In 24
      patients and 10 age-matched controls, the fasting serum concentrations of free
      IGF-I and -II were measured using ultrafiltration by centrifugation. In addition,
      GH, GH-binding protein, total IGFs, IGFBP-1 to -4, and IGFBP-3 proteolytic
      activity were measured. The IGFBPs were measured by both immunoassays and Western
      ligand blotting. Twelve of the patients were restudied 3 months after a minor
      increase in body mass index. In AN, the levels of GH-binding protein, free and
      total IGF-I, free IGF-II, and IGFBP-3 were significantly reduced; total IGF-II,
      IGFBP-2, and IGFBP-4 levels were unchanged; and IGFBP-1 was increased. No
      increased IGFBP-3 proteolytic activity could be detected in AN. In conclusion,
      the mechanisms responsible for the adaption of the GH-IGF-IGFBP axis in AN may be
      different from other catabolic conditions, because the low levels of free and
      total IGF-I in AN are not associated with increased IGFBP-3 proteolysis.

PMID- 10199779
TI  - Characterization of human iodothyronine sulfotransferases.
AB  - Sulfation is an important pathway of thyroid hormone metabolism that facilitates
      the degradation of the hormone by the type I iodothyronine deiodinase, but little
      is known about which human sulfotransferase isoenzymes are involved. We have
      investigated the sulfation of the prohormone T4, the active hormone T3, and the
      metabolites rT3 and 3,3'-diiodothyronine (3,3'-T2) by human liver and kidney
      cytosol as well as by recombinant human SULT1A1 and SULT1A3, previously known as
      phenol-preferring and monoamine-preferring phenol sulfotransferase, respectively.
      In all cases, the substrate preference was 3,3'-T2 >> rT3 > T3 > T4. The apparent
      Km values of 3,3'-T2 and T3 [at 50 micromol/L 3'-phosphoadenosine-5'
      phosphosulfate (PAPS)] were 1.02 and 54.9 micromol/L for liver cytosol, 0.64 and
      27.8 micromol/L for kidney cytosol, 0.14 and 29.1 micromol/L for SULT1A1, and 33
      and 112 micromol/L for SULT1A3, respectively. The apparent Km of PAPS (at 0.1
      micromol/L 3,3'-T2) was 6.0 micromol/L for liver cytosol, 9.0 micromol/L for
      kidney cytosol, 0.65 micromol/L for SULT1A1, and 2.7 micromol/L for SULT1A3. The
      sulfation of 3,3'-T2 was inhibited by the other iodothyronines in a concentration
      dependent manner. The inhibition profiles of the 3,3'-T2 sulfotransferase
      activities of liver and kidney cytosol obtained by addition of 10 micromol/L of
      the various analogs were better correlated with the inhibition profile of SULT1A1
      than with that of SULT1A3. These results indicate similar substrate specificities
      for iodothyronine sulfation by native human liver and kidney sulfotransferases
      and recombinant SULT1A1 and SULT1A3. Of the latter, SULT1A1 clearly shows the
      highest affinity for both iodothyronines and PAPS, but it remains to be
      established whether it is the prominent isoenzyme for sulfation of thyroid
      hormone in human liver and kidney.

PMID- 10199778
TI  - Galanin is released by adrenocorticotropin-secreting pituitary adenomas in vivo
      and in vitro.
AB  - Galanin, a brain-gut peptide, is also synthesized and released by the pituitary.
      In man, galanin-like immunoreactivity and galanin messenger RNA have been
      detected specifically in normal and tumoral corticotropes, but little is known
      about the production and release of galanin by the human pituitary. We evaluated
      galanin release by 5 ACTH-secreting pituitary adenomas in culture and plasma
      galanin concentrations in the inferior petrosal sinuses (IPSs) of 15 patients
      with Cushing's disease before and after CRH administration. For comparison, the
      galanin response to CRH was evaluated in 8 normal controls. Galanin secretion by
      pituitary tumor cultures ranged from 30-230 pmol/4 h. Incubation with CRH induced
      an increase in galanin concentrations (100 pM CRH: 151 +/- 32%; 1 nM CRH: 232 +/-
      43%; 10 nM CRH: 246 +/- 35%; and 100 nM CRH: 270 +/- 44% unstimulated levels at
      24 h, P < 0.05). The stimulatory effect of CRH seemed to be dose-dependent. Basal
      and CRH-stimulated ACTH and galanin concentrations also exhibited a strong
      positive correlation in single tumor cultures. At IPS sampling, mean basal plasma
      galanin concentrations in the dominant IPS were somewhat higher than those
      registered at the periphery (18.6 +/- 1.94 vs. 15.8 +/- 1.60 pmol/L, P = 0.05).
      Administration of CRH induced a modest but significant increase in galanin
      concentrations at all three sampling sites. No correlations were found between
      ACTH and galanin levels in the IPSs and at the periphery. Different from what was
      observed in patients with Cushing's disease, CRH did not modify plasma galanin
      concentrations in normal subjects. In conclusion, this study demonstrates that
      galanin is released by human tumoral corticotropes and responds to CRH. The role
      of locally produced galanin is, as yet, unknown but may possibly be that of a
      autocrine/paracrine modulator.

PMID- 10199780
TI  - Follicle-stimulating hormone-inhibin B interactions during the follicular phase
      of the primate menstrual cycle revealed by gonadotropin-releasing hormone
      antagonist and antiestrogen treatment.
AB  - The aim was to determine the pattern of inhibin A and inhibin B secretion during
      the ovulatory cycle of the macaque and to explore the effects of manipulating
      follicular phase FSH on inhibin B secretion by: 1) blocking the early follicular
      phase rise in FSH with GnRH antagonist treatment; 2) administering FSH in GnRH
      antagonist-treated animals; and 3) preventing the midfollicular phase decline in
      FSH by a specific antiestrogen. Treatment with GnRH antagonist, starting on day
      25 of the cycle, abolished the early follicular phase rise in FSH and the
      associated increase in inhibin B. The same treatment, followed by exogenous FSH,
      restored the secretion of inhibin B. Treatment with antiestrogen, commencing
      during the midfollicular phase, induced a supraphysiological rise in FSH,
      followed by a marked stimulation of inhibin B and estradiol secretion. Despite
      continued antiestrogen treatment, FSH secretion declined before peak values of
      inhibin B and estradiol were attained, implying a potential endocrine role for
      inhibin B, in addition to estradiol, in the negative feedback regulation of FSH.
      These results show that follicular phase FSH is the major stimulus for inhibin B
      secretion.

PMID- 10199781
TI  - Coexpression of alternatively spliced estrogen and progesterone receptor
      transcripts in human breast cancer.
AB  - Primary transcripts of the human estrogen receptor (ER) and progesterone receptor
      (PR) are subject to a number of alternative splicing events resulting in a range
      of variant messenger ribonucleic acid species in receptor-positive tissues.
      Despite in vitro demonstrations of a possible role for some of these variants in
      hormonal sensitivity, the clinical significance of this process is uncertain. In
      this study the coexpression of variant ER and PR transcripts has been documented
      by RT-PCR and Southern blot analysis in a series of receptor-positive breast
      tumors. In 35 ER-positive tumors, a common profile of variant ER transcripts was
      present, with all tumors containing the delta2ER and delta7ER, 94% containing the
      delta4ER, and 83% containing the delta5ER. In 25 of these cases, which were also
      PR positive, the most highly expressed PR variants, the delta4PR, delta6PR, and
      delta(4/2)PR, a transcript from which a 126-bp portion of PR exon 4 was deleted,
      were detected in over 90% of the cases. The alternatively spliced ER variants
      were expressed at higher relative levels than the PR species, which had mean
      levels of expression less than 10% that of wild-type PR. The most abundant
      species was the delta7ER, which was present at levels ranging from 29-83% of the
      wild type. There was no relationship between the level of delta7ER in individual
      tumors and the pattern of expression of the estrogen-responsive proteins PR and
      pS2. The common profile of alternatively spliced ER and PR transcripts in breast
      tumors means that this feature cannot be used as a discriminator of hormone
      responsiveness or other clinical end points. Further, the low level of expression
      of the majority of variant species calls into question their potential for
      impacting significantly on receptor function.

PMID- 10199782
TI  - Effects of thyroid hormones on apoptotic cell death of human lymphocytes.
AB  - Apoptosis plays a critical role in the development and homeostasis of tissues,
      especially those with high cell turnover such as the lymphoid system. We have
      examined the effects of thyroid hormones, TSH and TRH, on apoptosis of human T
      lymphocytes. We found that T lymphocytes cultured with T3 and T4, but not TSH nor
      TRH, in vitro showed enhanced apoptosis, evidenced by DNA ladder formation and
      characteristic morphological changes. In addition, prolonged cultivation with
      thyroid hormones of the lymphocytes further enhanced the extent of apoptosis. We
      also found that treatment with thyroid hormones of T lymphocytes induced
      reduction of mitochondrial transmembrane potential (delta psi) and production of
      reactive oxygen species, both of which are intimately associated with apoptotic
      cell death. In addition, cellular expression of antiapoptotic Bcl-2 protein was
      clearly reduced by the treatment of lymphocytes with thyroid hormones in vitro.
      Thus, T lymphocytes treated with thyroid hormones accompany reduction of Bcl-2
      protein expression, production of reactive oxygen species, and reduction of
      mitochondrial delta psi, resulting in apoptotic lymphocyte death. Moreover, we
      found that lymphocytes in patients with Graves' disease showed enhanced apoptosis
      compared with those in normal individuals. These results suggest that thyroid
      hormones have the potential to induce apoptotic cell death of human lymphocytes
      in vivo and in vitro.

PMID- 10199783
TI  - Prolonged exposure of human beta-cells to high glucose increases their release of
      proinsulin during acute stimulation with glucose or arginine.
AB  - The disproportionate hyperproinsulinemia in type 2 diabetes has been attributed
      to either a primary beta-cell defect or a secondary dysregulation of beta cells
      under sustained hyperglycemia. This study examines the effect of a 10- to 13-day
      exposure to 20 mmol/L glucose on subsequent proinsulin and insulin release by
      human islets isolated from nondiabetic donors. Compared to control preparations
      kept at 6 mmol/L glucose, the high glucose cultured beta-cells released more
      proinsulin and less insulin during perifusion at 5, 10, or 20 mmol/L glucose. The
      lower amounts of secreted insulin resulted from a marked reduction in cellular
      insulin content (5-fold lower than in controls). The higher amount of secreted
      proinsulin is attributed to the sustained state of cellular activation that is
      known to occur after prolonged exposure to high glucose levels. This activated
      state of the beta-cell population is also held responsible for its higher
      secretory responsiveness to 5 mmol/L arginine at a submaximal (5 mmol/L) glucose
      concentration (8-fold higher proinsulin levels than in the control population).
      It results, together with the reduction in cellular insulin content, in 7- to 10
      fold higher proinsulin over insulin ratios in the medium; at 5 mmol/L glucose,
      this extracellular ratio is similar to that in the cells. These data add direct
      support to the view that a disproportionate hyperproinsulinemia can result from a
      sustained activation of human beta-cells after prolonged exposure to elevated
      glucose levels.

PMID- 10199784
TI  - Expression of the functional extracellular domain of human thyrotropin receptor
      using a vaccinia virus system: its purification and analysis of autoantibody
      binding.
AB  - We produced substantial amount of the extracellular domain of the human TSH
      receptor (TSHRE) that has a tag of six histidines at C-terminus as a soluble form
      in the human cell line HeLa using a vaccinia virus system. By sequential nickel
      chelating and lentil lectin column chromatography, TSHRE was purified to about
      70% purity, with the recovery of around 0.1-0.2 mg TSHRE/L culture (5 x 10(8)
      cells/liter culture). The purified TSHRE interacted with TSH as well as Graves'
      autoantibodies to TSHR. However, the affinity of TSHRE for TSH was much lower
      than that of intact TSHR. The IC50 value for inhibition of TSH-dependent cAMP
      synthesis by TSHRE was about 10(-8) mol/L. Most importantly, the purified TSHRE
      inhibited the binding of the IgG of Graves' patients to thyroid membrane. About 1
      microg/mL (2 x 10(-8) mol/L) TSHRE neutralized most of the autoantibody activity
      of patients' sera tested in the TSH binding inhibitory immunoglobulin (TBII)
      assay. Moreover, this protein neutralized thyroid stimulatory antibody-induced
      cAMP synthesis with an IC50 of 1 x 10(-9) mol/L and completely at 0.5-1 microg/mL
      (1-2 x 10(-8) mol/L). In the simple enzyme-linked immunosorbent assay, the TSHRE
      immobilized on the wells coated with nickel showed significantly higher binding
      with the IgGs from Graves' patients than in those from normal individuals. This
      autoantibody-reactive TSHRE will be useful for further studies on the diagnosis,
      pathogenesis, and the development of therapy of Graves' disease.

PMID- 10199785
TI  - Heritability of pancreatic beta-cell function among nondiabetic members of
      Caucasian familial type 2 diabetic kindreds.
AB  - Both defective insulin secretion and insulin resistance have been reported in
      relatives of type 2 diabetic subjects. We tested 120 members of 26 families with
      a type 2 diabetic sibling pair with a tolbutamide-modified, frequently sampled
      i.v. glucose tolerance test to determine the insulin sensitivity index (S(I)) and
      acute insulin response to glucose (AIRglucose). A measure of beta-cell
      compensation for insulin sensitivity was calculated as the product S(I) x
      AIRglucose, based on the demonstrated hyperbolic relationship between insulin
      sensitivity and insulin secretion. A percentile score for this compensation was
      assigned based on published values. Of the 120 family members, 26 had previously
      diagnosed impaired glucose tolerance on oral testing, and 94 had normal glucose
      tolerance tests. As a group, family members showed a significantly lower S(I) x
      AIRglucose than a similar, previously reported, control population, even when
      impaired glucose tolerance members were excluded. We performed a multivariate
      analysis of diabetes status, S(I), AIRglucose and to estimate the heritability of
      each trait and the genetic and environmental correlations between traits. We
      estimated the heritability of S(I) x AIRglucose to be 67 +/- 3% when all members
      were included and 70 +/- 4% when only normal glucose tolerance members were
      considered. Both AIRglucose and S(I) were also familial, albeit with lower
      heritabilities (38 +/- 1% and 38 +/- 2%, respectively, for all family members).
      Both S(I) x AIRglucose and S(I) showed strong negative genetic correlations with
      diabetes (-85 +/- 3% and -87 +/- 2%, respectively, all family members), whereas
      AIRglucose did not correlate with diabetes. We conclude that insulin secretion,
      as measured by S(I) x AIRglucose, is decreased in nondiabetic members of familial
      type 2 diabetic kindreds, that S(I) x AIRglucose in these high risk families is
      highly heritable, and that the same polygenes may determine diabetes status and a
      low S(I) x AIRglucose. Our data suggest that insulin secretion, when expressed as
      an index normalized for insulin sensitivity, is more familial than either insulin
      sensitivity or first phase insulin secretion alone and may be a very useful trait
      for identifying genetic predisposition to type 2 diabetes.

PMID- 10199786
TI  - The presence or absence of a retroviral long terminal repeat influences the
      genetic risk for type 1 diabetes conferred by human leukocyte antigen DQ
      haplotypes. Belgian Diabetes Registry.
AB  - Major genetic susceptibility to type 1 diabetes mellitus maps to the human
      leukocyte antigen (HLA) region on chromosome 6p. During evolution, endogenous
      retroviral long terminal repeats (LTR) have been integrated at several sites
      within this region. We analyzed the presence of a solitary HERV-K LTR in the HLA
      DQ region (DQ-LTR3) and its linkage to DRB1, DQA1, and DQB1 haplotypes derived
      from 246 German and Belgian families with a patient suffering from type 1
      diabetes mellitus. Segregation analysis of 984 HLA DQA1/B1 haplotypes showed that
      DQ-LTR3 is linked to distinct DQA1 and DQB1 haplotypes but is absent in others.
      The presence of DQ-LTR3 on HLA DQB1*0302 haplotypes was preferentially
      transmitted to patients from heterozygous parents (82%; P < 10(-6)), in contrast
      to only 2 of 7 DQB1*0302 haplotypes without DQ-LTR3. Also, the extended HLA
      DRB1*0401, DQB1*0302 DQ-LTR3-positive haplotypes were preferentially transmitted
      (84%; P < 10(-6)) compared with 1 of 6 DR-DQ matched DQ-LTR3 negative haplotypes.
      DQ-LTR3 is missing on most DQB1*0201 haplotypes, and those LTR3 negative
      haplotypes were also preferentially transmitted to patients (80%; P < 10(-6)),
      whereas DQB1*0201 DQ-LTR3-positive haplotypes were less often transmitted to
      patients (36%). Other DQA1/B1 haplotypes did not differ for DQ-LTR3 between
      transmitted and nontransmitted haplotypes. Thus, the presence of DQLTR3 on HLA
      DQB1*0302 and its absence on DQB1*0201 haplotypes are independent genetic risk
      markers for type 1 diabetes.

PMID- 10199787
TI  - Increased sulfatation of orbital glycosaminoglycans in Graves' ophthalmopathy.
AB  - Accumulation of interstitial glycosaminoglycans (GAG) in orbital tissue of
      patients with Graves' ophthalmopathy (GO) leads to edema, increased orbital
      pressure, and proptosis. In this study, a new, highly sensitive, high performance
      liquid chromatography method was developed to determine the altered concentration
      and biochemical composition of different GAG polymers in orbital connective
      tissue of 27 GO patients and 18 controls. GAG were isolated by tissue
      homogenization and digestion, followed by sequential enzymatic GAG hydrolysis and
      high performance liquid chromatographic analysis of the resulting alpha,beta
      unsaturated disaccharides. High recovery rates of 78 +/- 6% (mean +/- SE) and a
      detection limit of 4.0 microg/L (0.01 micromol/L) were obtained. Total tissue GAG
      amounted to 254 +/- 16 microg/g wet tissue wt in patients and 150 +/- 13 microg/g
      (P < 0.0001) in controls. Regarding the GAG polymers, marked differences were
      detected between patients and controls (chondroitin sulfate, 127 +/- 13 vs. 47 +/
      5 microg/g; hyaluronic acid, 56 +/- 5 vs. 34 +/- 4 microg/g; both P < 0.0001;
      dermatan sulfate, 77 +/- 6 vs. 69 +/- 6 microg/g; P < 0.05). In patients,
      chondroitin sulfate was the major GAG component (48 +/- 6 vs. 31 +/- 5% of total
      GAG in controls), whereas dermatan sulfate was dominant in controls (46 +/- 8%
      vs. 30 +/- 5%). The sulfated disaccharide digestion products were markedly
      increased (P < 0.0001) in patients, and the ratio of sulfated vs. total
      disaccharide content was 85 +/- 6% vs. 65 +/- 5% (P < 0.05) in patients and
      controls, respectively. As accumulation of negatively charged sulfate residues in
      GAG disaccharides results in enhanced water-binding capacity, beside inflammation
      and increased volume of the orbital adipose tissue, the altered structure and
      nature of sulfated GAG units in the orbit may be responsible for the pathogenic
      changes in Graves' ophthalmopathy.

PMID- 10199788
TI  - Characterization of Prophet of Pit-1 gene expression in normal pituitary and
      pituitary adenomas in humans.
AB  - Prophet of Pit-1 (Prop-1), which is a paired-like homeodomain transcription
      factor, is capable of binding to sites in an early enhancer of the Pit-1 gene and
      regulating its expression. According to a previous report, Prop-1 messenger RNA
      (mRNA) is expressed in the developing pituitary gland before Pit-1 mRNA
      expression and maximum expression are observed at e 12.0. After e 14.5, Prop-1
      mRNA expression rapidly decreases, and only trace amounts of mRNA are detectable
      in adult mouse pituitary. Human Pit-1 is expressed considerably, not only in
      normal adult pituitary but also in pituitary adenomas, so we studied human Prop-1
      gene expression in adult pituitary and pituitary adenomas. We also cloned human
      Prop-1 complementary DNA (cDNA) and sequenced the Prop-1 cDNAs in pituitary
      adenomas. The amino acid sequence of human Prop-1 cDNA that we cloned was
      identical to that of the previously reported sequence, except Thr substituted at
      codon 142 instead of Ala. This amino acid substitution is considered to be a
      polymorphism because it did not alter transcriptional activity, and 7 of 28
      alleles were Ala. Human Prop-1 transcript was detected in normal adult pituitary,
      by Northern blot analysis, and in all pituitary adenomas examined by RT-PCR
      analysis. The expression of human Prop-1 in pituitary adenomas was confirmed by
      in situ hybridization in one of the somatotroph adenomas. The sequence analysis
      of human Prop-1 cDNAs in these pituitary adenomas revealed that there were no
      mutations, except 5 silent nucleic acid substitutions, suggesting that mutations
      of Prop-1 gene do not represent a frequent mechanism of human pituitary
      tumorigenesis.

PMID- 10199789
TI  - Urocortin stimulates placental adrenocorticotropin and prostaglandin release and
      myometrial contractility in vitro.
AB  - Urocortin is a new member of the CRF family. Multiple biological effects for
      urocortin have been shown in rats and in some in vitro models, showing a
      modulatory role in hormonal and behavioral functions. Human placenta expresses
      urocortin, but no information is available on the possible local biological
      actions. The aim of the present study was to evaluate the effect of urocortin on
      placental ACTH and prostaglandin (PG) secretion, as well as on myometrial
      contractility. Various in vitro models were used. For investigating the effect of
      urocortin on ACTH release, primary cultures of human trophoblast cells were used.
      Culture media, collected before and after 3 h exposure to different doses of
      urocortin and ACTH, were measured by RIA. Trophoblast tissue explants were
      incubated for 24 h in the presence of increasing doses of urocortin, and
      prostaglandin E2 (PGE2) levels were measured by RIA. Strips of myometrial tissue
      were incubated in an organ bath and connected to an isometric smooth-muscle
      transducer in the presence of urocortin, with or without prostaglandin F2alpha
      (PGF2a). In all these experiments, the effect of astressin (a CRF receptor
      antagonist) on urocortin-induced actions and the effect of equimolar doses of CRF
      were evaluated. A dose-related increase of trophoblast ACTH or PGE2 was induced
      by urocortin, whereas astressin inhibited urocortin-stimulated ACTH or PGE2
      release. Equimolar doses of CRF showed a similar effect on both ACTH and PGE2.
      Urocortin increased PGF2alpha-induced myometrial contractility, and this effect
      was completely abolished by the addition of astressin. The present study showed
      that human urocortin stimulates placental secretion of ACTH and PGE2, and
      modulates myometrial contractility, suggesting a role for this peptide in
      placental and intrauterine CRF pathways.

PMID- 10199790
TI  - Evidence for genetic transmission of thyroid peroxidase autoantibody epitopic
      "fingerprints".
AB  - Autoimmune thyroid disease is characterized by the tendency to cluster in
      families and by IgG class autoantibodies to antigens such as thyroid peroxidase
      (TPO). The epitopes recognized by polyclonal serum autoantibodies can be
      quantitatively fingerprinted using four recombinant human TPO autoantibodies
      (expressed as Fab) that define A and B domain epitopes in an immunodominant
      region. To determine whether these fingerprints are genetically transmitted, we
      analyzed fingerprints of 63 members of 7 multiplex Old Order Amish families and
      17 individuals from 4 Hashimoto thyroiditis families. Inhibition of serum
      autoantibody binding to [125I]TPO by the recombinant Fab was used to assess
      recognition of the TPO immunodominant region (4 Fab combined) and recognition of
      domain A or B (individual Fab). Complex segregation analysis was performed using
      a unified model (POINTER). For the 4 Fab combined inhibition phenotype, the no
      transmission model was rejected (chi2(4) = 20.67; P < 0.0032), and the most
      parsimonious model includes a major gene effect. More importantly, evidence for
      genetic transmission was obtained for the phenotype defined by the ratio of
      inhibition by subdomain Fab B1:B2. Thus, for this ratio (reflecting recognition
      of the B domain), the no transmission model was rejected chi2(4) = 63.59; P <
      0.000008). Moreover, the polygenic hypothesis could be rejected, but not the
      major locus hypothesis, suggesting that major genes might be involved in familial
      transmission of this trait. In conclusion, our findings suggest that autoantibody
      recognition of the TPO immunodominant region and the TPO B domain is genetically
      transmitted. These data may open the way to the identification by candidate
      analysis or positional cloning of at least one gene responsible for the
      development of Hashimoto's thyroiditis.

PMID- 10199791
TI  - The effect of estrogen on aromatase and vascular endothelial growth factor
      messenger ribonucleic acid in the normal nonhuman primate mammary gland.
AB  - In the present study, the baboon was used as a model to investigate the effects
      of steroid hormones on vascular endothelial growth factor (VEG/PF) and aromatase
      expression and on proliferation of the normal mammary gland. Immunocytochemistry
      revealed that both aromatase and VEG/PF were expressed in the epithelial cells of
      the terminal ductal lobular units. Mammary tissue biopsies were obtained from
      female baboons during the follicular and luteal phases of the menstrual cycle, 4
      weeks after ovariectomy (OVX), and after 2 weeks of treatment with estradiol
      benzoate (E2B; 500 microg/day, i.m.). Although there was little apparent
      difference in aromatase messenger ribonucleic acid (mRNA) in tissue from
      follicular and luteal phases or after ovariectomy, aromatase mRNA was decreased
      in tissue from ovariectomized (OVX) animals treated for 2 weeks with E2B.
      Furthermore, aromatase activity in tissue from these animals was markedly reduced
      compared to activity in tissue from the OVX animals before treatment (P < 0.001).
      In one animal in which mammary aromatase activity was measured sequentially
      during the follicular and luteal phases, aromatase activity was increased
      significantly after OVX and was reduced to the level in the intact animal by
      subsequent treatment with E2B. This effect on both aromatase activity and mRNA
      occurred rapidly 2 and 4 h after injection with E2B. In contrast to its effect on
      aromatase, E2B treatment of OVX animals stimulated VEG/PF mRNA 2 and 4 h after
      injection. In histoculture of mammary biopsies from these animals in the
      follicular and luteal phases of the menstrual cycle or after OVX, [3H]thymidine
      incorporation was increased significantly by incubation with testosterone (T) as
      well as estrogen (P < 0.01). The effect of T was blocked by aromatase inhibitor,
      4-hydroxyandrostenedione, suggesting that the tissue is responsive to E produced
      by aromatization of T in the tissue. When mammary tissue from OVX animals was
      cultured with T, there was a significantly greater increase in [3H]thymidine
      incorporation than in histocultures of tissue from intact animals (P < 0.01).
      However, in histocultures of tissue from the OVX animals treated with E2B (500
      microg) for 2 weeks, [3H]thymidine incorporation was similar to the level in
      tissue of intact animals incubated with T. No significant changes occurred in
      [3H]thymidine incorporation with the nonaromatizable androgen dihydrotestosterone
      or progesterone alone. These findings suggest that estrogens produced locally by
      aromatization of T have a functional role in mammary tissue. Aromatase expressed
      in the mammary gland could be important in maintaining local estrogen
      concentrations, particularly after menopause. Estrogen appears to regulate
      transcription of both aromatase and VEG/PF in the mammary gland, suggesting a
      regulatory loop by which local estrogens could stimulate VEG/PF production. Thus,
      paracrine/autocrine mechanisms that can enhance the proliferation of malignant
      cells and their metastatic spread already exist before transformation.

PMID- 10199792
TI  - Two novel cysteine substitutions (C1263R and C1995S) of thyroglobulin cause a
      defect in intracellular transport of thyroglobulin in patients with congenital
      goiter and the variant type of adenomatous goiter.
AB  - We analyzed the thyroglobulin (Tg) gene of 2 unrelated patients with congenital
      goiter and the Tg gene of 2 siblings with the variant type of adenomatous goiter.
      The clinical characteristics of the patients with congenital goiter and the
      variant type of adenomatous goiter were very similar, except for serum Tg levels,
      which were less than 15 pmol/L in the patients with congenital goiter, but 117
      181 pmol/L in the patients with the variant type of adenomatous goiter (normal,
      15-50 pmol/L). The tissue content of Tg in the thyroid glands of all 4 patients
      was reduced at 0.9-3.8% of total protein (normal, 19-40%). The missense mutation
      C1263R was detected in the 2 unrelated patients with congenital goiter; the
      pedigree study showed an autosomal recessive pattern of inheritance. In the 2
      siblings with the variant type of adenomatous goiter, the missense mutation
      C1995S was homozygously detected. In the Tg complementary DNA of 110 normal
      subjects, the allelic frequencies of the C1263R and C1995S mutations were each
      less than 0.5%. Also in the normal subjects were detected 35 nucleotide
      polymorphisms, the insertion of 3 nucleotides, and 1 alternative splicing, each
      of which was not associated with any specific thyroid disease. From these data,
      the molecular mechanism of the C1263R and C1995S mutations was elucidated. We
      first analyzed the carbohydrate residues of C1263R Tg and C1995S Tg. Sensitivity
      to treatment by endoglycosidase H suggests that C1263R Tg and C1995S Tg were
      retained in the endoplasmic reticulum (ER). Also, the presence of endoglycosidase
      H-resistant Tg as well as endoglycosidase H-sensitive Tg in the patients with the
      variant type of adenomatous goiter suggests that a fraction of C1995S Tg was
      transported to the Golgi and associated with the mildly increased serum Tg
      levels. Native PAGE and Western blot analysis with anti-Tg antibody showed that
      C1263R Tg and C1995S Tg form high mol wt aggregates in the ER. Our results
      suggest that missense mutations that replace cysteine with either arginine or
      serine cause an abnormal three-dimensional structure of Tg. Such misfolded Tg
      polypeptides are retained in the ER as high mol wt aggregates.

PMID- 10199793
TI  - Placental glucose transporter expression is regulated by glucocorticoids.
AB  - Although glucocorticoids play important roles in development and fetal
      programming, they are widely used for treatment of a variety of diseases during
      pregnancy. In various tissues, glucocorticoids down-regulate glucose transport
      systems; however, their effects on glucose transporters in the placenta are
      unknown. In the present study, the glucose carrier proteins GLUT1 and GLUT3 were
      localized in the trophoblast and endothelium of the human, rat, and mouse
      placenta. Subsequently, it was investigated whether glucocorticoids affect
      messenger ribonucleic acid and protein expression of these molecules by Northern
      and Western blotting using 1) human term placental trophoblast cells cultured in
      the presence or absence of 0.5, 5, and 50 micromol/L triamcinolone; 2) placentas
      of rats that received a single i.p. dose of 0.38 mg/kg triamcinolone; and 3)
      placentas of transgenic mice bearing an antisense glucocorticoid receptor gene
      construct. In all of these systems, both glucose transporters were significantly
      down-regulated (P < 0.05), with the exception of increased GLUT3 messenger
      ribonucleic acid and protein levels in transgenic mice. The results demonstrate
      that triamcinolone is a potent regulator of placental GLUT1 and GLUT3 expression
      involving the glucocorticoid receptor. We speculate that impaired expression of
      placental glucose transporters after glucocorticoid administration might
      contribute to the adverse side-effects, the foremost of which is a growth
      retarded fetus, of this treatment during pregnancy.

PMID- 10199794
TI  - 11Beta-hydroxysteroid dehydrogenase type 2 and mineralocorticoid receptor in
      human fetal development.
AB  - 11Beta-Hydroxysteroid dehydrogenase type II (11betaHSD2) confers specificity on
      the mineralocorticoid receptor (MR) by converting biologically active
      glucocorticoids to inactive 11-keto metabolites. The biological significance of
      11betaHSD2 activity during fetal development is currently being explored, but the
      temporal and spatial distributions of the enzyme and receptor have not been
      examined. We therefore examined their distributions during various stages of
      human fetal development using immunohistochemistry. Both 11betaHSD2 and MR
      immunoreactivity were detected in the distal convoluted and collecting tubules of
      the kidney from early in gestation. Fetal skin, intermediate layer of the
      epidermis, peridermal cells, and hair follicles were positive for both 11betaHSD2
      and MR. Weak 11betaHSD2 and MR immunoreactivity was detected in the superficial
      ciliated epithelium of the esophagus, the deep layer of gastric epithelial cells,
      and the superficial epithelium of the small intestine. Columnar epithelium in the
      terminal bronchiolar budding component of fetal lung and tracheal and bronchial
      ciliated epithelium were also positive for MR and 11betaHSD2 from early
      gestation. Colonic epithelium and pancreatic exocrine duct cells, which
      demonstrated marked immunoreactivity of both MR and 11betaHSD2 in the adult, did
      not express MR and 11betaHSD2 until very late in gestation. These results imply
      that mineralocorticoid action in the upper fetal gastrointestinal tract, kidney,
      skin, and lung is facilitated by 11betaHSD2 and is involved in water and
      electrolyte transport between fetus and amniotic fluid as well as fetal urine
      production.

PMID- 10199795
TI  - A germline mutation of the thyrotropin receptor gene associated with
      thyrotoxicosis and mitral valve prolapse in a Chinese family.
AB  - Activating mutations of the TSH receptor (TSH-R) have been reported to result in
      toxic adenomas, multinodular goiters, sporadic neonatal hyperthyroidism, and
      familial autosomal dominant nonautoimmune hyperthyroidism. To date, all
      descriptions of such mutations, whether somatic or genomic, have been confined to
      the Caucasian population. We describe a Chinese family in whom a germline proline
      to serine substitution in position 639 resulted in familial thyrotoxicosis. This
      constitutively activating mutation has been previously described in a
      hyperfunctioning thyroid nodule. The three children in this family developed
      thyrotoxicosis during childhood; their father was diagnosed as thyrotoxic at the
      age of 38 yr. Two of the children and the father had mitral valve prolapse (MVP)
      associated with mitral regurgitation. There was a close temporal relationship
      between the onset of thyrotoxicosis and the diagnosis of mitral valvular disease
      in these patients. An increased prevalence of MVP has been reported in Graves'
      disease and chronic lymphocytic thyroiditis, but the pathophysiological
      mechanisms linking MVP and autoimmune thyroid disease are still not understood.
      This is the first report of an association between activating TSH-R mutations and
      MVP. We postulate that TSH-R activation may increase the clinical expression of
      MVP in genetically predisposed individuals.

PMID- 10199796
TI  - Changes in tissue transglutaminase activity and expression during retinoic acid
      induced growth arrest and apoptosis in primary cultures of human epithelial
      prostate cells.
AB  - We treated primary epithelial cells from human normal prostate (NEPC) and
      prostate cancer (CEPC) with all-trans-retinoic acid (RA) to study whether it
      regulates the activity of tissue transglutaminase (tTGase), an enzyme that
      accumulates in cells undergoing apoptosis. tTGase activity was assessed by
      [14C]spermidine incorporation; tTGase, P53, Bcl-2, and p21 protein levels were
      evaluated by Western blotting; and RA receptors (RAR alpha, -beta, and -gamma),
      tTGase, retinol-binding protein (RBP), and cellular RBP type I transcripts were
      determined by semiquantitative RT-PCR. After 72-96 h of 10(-6) mol/L RA
      treatment, cell growth inhibition and apoptosis were associated with increased
      tTGase activity in both NEPC and CEPC, and with increased tTGase protein and
      messenger ribonucleic acid levels only in NEPC. Moreover, RA down-regulated RAR
      alpha and -beta and increased RBP messenger ribonucleic acid levels in NEPC,
      whereas it increased RAR beta gene expression and decreased Bcl-2 protein levels
      in CEPC. Our results suggest that RA induces tTGase gene expression and enzyme
      activity in normal prostate cells, and that RA-regulated pathways are impaired in
      cancer cells. Moreover, down-regulation of Bcl-2 protein and up-regulation of RAR
      beta suggest that retinoid may act on the genetic defect responsible for prostate
      cancer progression.

PMID- 10199797
TI  - Restoration of reproductive potential by lifestyle modification in obese
      polycystic ovary syndrome: role of insulin sensitivity and luteinizing hormone.
AB  - Weight reduction and exercise have been shown to help with menstrual disturbance
      and infertility in obese women with polycystic ovary syndrome. We studied the
      relationship between insulin sensitivity and ovulation patterns in 18 infertile
      anovulatory obese polycystic ovary syndrome (PCOS) women (NO) with normal glucose
      tolerance, aged between 22-39 yr with a body mass index of 27-45 kg/m2, before
      and after a 6-month diet and exercise program. This program promotes healthy
      lifestyle factors, but does not lead to rapid weight loss. The anthropometric,
      metabolic, and endocrine factors of these subjects were compared to those of 10
      age- and weight-matched PCOS women with regular monthly ovulation (RO). Before
      lifestyle modification, the anovulatory subjects had greater central obesity than
      regular ovulators, as assessed by percent central fat (NO, 45.7 +/- 0.8%; RO,
      42.2 +/- 1.6%; P < 0.05), higher glucose increment after glucose challenge (NO,
      10.1 +/- 1.0 mmol/L; RO, 6.4 +/- 1.1 mmol/L; P < 0.02), lower insulin sensitivity
      index (NO, 1.2 +/- 0.2; RO, 2.8 +/- 0.6 micromol/kg x min/pmol/L; P < 0.005),
      higher plasma LH (NO, 8.9 +/- 0.9; RO, 4.6 +/- 0.9 IU/L; P < 0.005), and lower
      plasma sex hormone-binding globulin (NO, 18.0 +/- 2.5; RO, 27.8 +/- 5.7 nmol/L; P
      < 0.05]. Anovulatory subjects were classified as responders (R) to the
      intervention if they regained ovulation during the study. As a result of
      intervention, R showed an 11% reduction in central fat, a 71% improvement in
      insulin sensitivity index, a 33% fall in fasting insulin levels, and a 39%
      reduction in LH levels. None of these parameters changed significantly in
      nonresponders (NR). At the end of the study, R had lower fasting insulin (R, 13.6
      +/- 1.7; NR, 23.0 +/- 3.5 mU/L) and LH levels (R, 5.0 +/- 1.7; NR, 7.4 +/- 1.4
      IU/L), but similar androgen levels compared to NR. We conclude that lifestyle
      modification without rapid weight loss leads to a reduction of central fat and
      improved insulin sensitivity, which restores ovulation in overweight infertile
      women with PCOS. Lifestyle modification is the best initial management for obese
      women seeking to improve their reproductive function.

PMID- 10199798
TI  - Pharmacokinetic profiles of repaglinide in elderly subjects with type 2 diabetes.
AB  - Pharmacokinetic profiles of single- and multiple-dose regimens of repaglinide
      were evaluated in 12 elderly subjects with type 2 diabetes. On day 1, following a
      10-hour fast, subjects received a single 2-mg dose of repaglinide. Starting on
      day 2 and continuing for 7 days, each subject received a 2-mg dose of repaglinide
      15 minutes before each of the three main meals. On day 9, subjects received a
      single 2-mg dose of repaglinide. Pharmacokinetic profiles, including area under
      the curve (AUC), log(AUC), maximal concentration (Cmax), log(Cmax), time to
      maximal concentration (Tmax), and half-life (T(1/2)), were determined at
      completion of the single- and multiple-dose regimens (days 1 and 9,
      respectively). Trough repaglinide values were collected on days 2 through 7. The
      mean log(AUC) values after multiple dosing were significantly higher than the
      values obtained after a single dose. The mean values for log(Cmax), and Tmax were
      comparable after each dosing regimen. The T(1/2) of repaglinide after multiple
      dosing was 1.7 hours. The trough values for repaglinide were low. No hypoglycemic
      events were reported. The pharmacokinetic profiles of repaglinide after single-
      and multiple-dose regimens were similar, and repaglinide was well tolerated by
      elderly subjects with type 2 diabetes.

PMID- 10199799
TI  - Insulin-like growth factor-II mediates the steroidogenic and growth promoting
      actions of follicle stimulating hormone on human ovarian pre-antral follicles
      cultured in vitro.
AB  - FSH is important for ovarian antral follicle growth and steroidogenesis,
      processes in the human that are believed to be mediated by IGF-II. The objective
      of this study was to determine if human ovarian pre-antral follicles are also FSH
      and IGF-II-responsive, since the clinical questions and mechanisms underlying
      the effects on the pre-antral follicle pool of exogenously administered
      gonadotropins for fertility therapy and elevated endogenous gonadotropins in the
      perimenopause remain unanswered. Class 2 preantral follicles were isolated from
      human premenopausal ovaries (n=6) and cultured in vitro with androstenedione and
      either no additives or with FSH or IGF-II. FSH (100 ng/mL) stimulated estradiol
      (E2) production by 3.58 +/- 0.4 fold over 48 hr, compared to controls without
      FSH. This effect was completely inhibited in the presence of the IGF-II
      antagonist, IGF binding protein-4 (IGFBP-4). IGF-II also stimulated E2 production
      by preantral follicles with doses as low as 1 ng/mL and within 24 hr of
      treatment. Maximal response of 3- to 9-fold above control was achieved with 100
      ng/mL of IGF-II between 96-120 hr of culture. IGFBP-4 completely inhibited E2
      production to basal levels. FSH stimulated IGF-II mRNA in pre-antral follicles
      about 4-fold, determined by RT-PCR. FSH also stimulated follicle growth,
      determined by light microscopy, 50-68% over 48 hr, compared to controls
      (P<0.001), a process that was inhibited in the presence of IGFBP-4. Cumulatively,
      these data support IGF-II as a mediator of FSH action on human preantral
      follicles.

PMID- 10199800
TI  - Several mutations in the melanocortin-4 receptor gene including a nonsense and a
      frameshift mutation associated with dominantly inherited obesity in humans.
AB  - The melanocortin-4 receptor gene (MC4-R) has been implicated in weight
      regulation. Recently, two independent groups reported frameshift mutations
      associated with a dominant form of obesity (1, 2). We screened the coding region
      of the MC4-R in 306 extremely obese children and adolescents (mean body mass
      index: BMI 34.4 +/- 6.6 kg/m2), 25 healthy underweight students (mean BMI 17.1 +/
      0.8 kg/m2), 52 normal weight individuals (mean BMI 22.0 +/- 1.0 kg/m2), 51
      inpatients with anorexia nervosa (AN, DSM IV criteria, mean BMI 14.3 +/- 1.5
      kg/m2) and 27 patients with bulimia nervosa (BN, DSM IV criteria, mean BMI 21.7
      +/- 5.8 kg/m2) by single strand conformation polymorphism analysis (SSCP).
      Several mutations were identified, including the frameshift mutation described
      (1). The mutations were as follows: a) The deletion of 4 bp (delta of CTCT at
      codon 211) results in a frameshift, thus rendering a truncated protein. This
      mutation has been assumed to be associated with dominantly-inherited morbid
      obesity in humans (1). Both the index patient (BMI 42.06 kg/m2, height 171 cm,
      age 19.6 years) and her mother (BMI 37.55 kg/m2, height 164 cm, age 42.5 years)
      were heterozygous for the deletion. b) A nonsense mutation at position 35 of the
      MC4-R was detected in two obese probands (BMI 31.29 kg/m2 and BMI 45.91 kg/m2).
      This mutation leads to a truncated protein that encompasses the N-terminal
      extracellular domain. Both carriers additionally showed (c) a missense mutation
      (Asp-37-Val). In both of these cases Tyr-35-Stop and Asp-37-Val were maternally
      transmitted, thus these variations form a haplotype. d) e) A male obese proband
      harbored two missense mutations (Ser-30-Phe, Gly-252-Ser). f)-i) Four different
      missense mutations (Pro-78-Leu, Thr-112-Met, Arg-165-Trp, Ile-317-Thr) were
      detected in four different male probands, respectively. All of these mutations (a
      to i) were found solely in extremely obese individuals whose BMIs were all above
      the 99th percentile. j) A silent mutation (C-579-T, Val-193-Val) was detected in
      a male underweight individual. k) A previously described polymorphism (Val-103
      Ile; 3) was detected with similar frequencies in all different study groups. 1)
      We identified a novel polymorphism (Ile-251-Leu) with similar allele frequencies
      in all groups under study. In conclusion, our data indicate that mutations in the
      MC4-R are not uncommon. Whereas our data support the evidence for dominantly
      inherited obesity as revealed by the three obese probands with haplo
      insufficiency, the functional significance of the missense mutations remains to
      be determined.

PMID- 10199801
TI  - Comment on calcium-regulated renal calcium handling in healthy men.

PMID- 10199802
TI  - Comment--Is there a role for low doses of mitotane (o,p'-DDD) as adjuvant therapy
      in adrenocortical carcinoma?

PMID- 10199803
TI  - Uneventful pregnancy in an acromegalic patient treated with slow-release
      lanreotide: a case report.

PMID- 10199804
TI  - Comment on "true" and "apparent" bone density measurement in children with GH
      deficiency.

PMID- 10199805
TI  - Comment on Carney complex and related syndromes and their genetic loci.

PMID- 10199806
TI  - Cellular microbiology: can we learn cell physiology from microorganisms?
AB  - Cellular microbiology is a new discipline that is emerging at the interface
      between cell biology and microbiology. The application of molecular techniques to
      the study of bacterial pathogenesis has made possible discoveries that are
      changing the way scientists view the bacterium-host interaction. Today, research
      on the molecular basis of the pathogenesis of infective diarrheal diseases of
      necessity transcends established boundaries between cell biology, bacteriology,
      intestinal pathophysiology, and immunology. The use of microbial pathogens to
      address questions in cell physiology is just now yielding promising applications
      and striking results.

PMID- 10199807
TI  - Desensitization of P2Y2 receptor-activated transepithelial anion secretion.
AB  - Desensitization of P2Y2 receptor-activated anion secretion may limit the
      usefulness of extracellular nucleotides in secretagogue therapy of epithelial
      diseases, e.g., cystic fibrosis (CF). To investigate the desensitization process
      for endogenous P2Y2 receptors, freshly excised or cultured murine gallbladder
      epithelia (MGEP) were mounted in Ussing chambers to measure short-circuit current
      (Isc), an index of electrogenic anion secretion. Luminal treatment with
      nucleotide receptor agonists increased the Isc with a potency profile of ATP =
      UTP > 2-methylthioATP >> alpha,beta-methylene-ATP. RT-PCR revealed the expression
      of P2Y2 receptor mRNA in the MGEP cells. The desensitization of anion secretion
      required a 10-min preincubation with the P2Y2 receptor agonist UTP and increased
      in a concentration-dependent manner (IC50 approximately 10(-6) M). Approximately
      40% of the anion secretory response was unaffected by maximal desensitizing
      concentrations of UTP. Recovery from UTP-induced desensitization was rapid (<10
      min) at preincubation concentrations less than the EC50 (1.9 x 10(-6) M) but
      required progressively longer time periods at greater concentrations. UTP-induced
      total inositol phosphate production and intracellular Ca2+ mobilization
      desensitized with a concentration dependence similar to that of anion secretion.
      In contrast, maximal anion secretion induced by Ca2+ ionophore ionomycin was
      unaffected by preincubation with a desensitizing concentration of UTP. It was
      concluded that 1) desensitization of transepithelial anion secretion stimulated
      by the P2Y2 receptor agonist UTP is time and concentration dependent; 2) recovery
      from desensitization is prolonged (>90 min) at UTP concentrations >10(-5) M; and
      3) UTP-induced desensitization occurs before the operation of the anion secretory
      mechanism.

PMID- 10199808
TI  - Targeted disruption of the murine Nhe1 locus induces ataxia, growth retardation,
      and seizures.
AB  - In most cells, the ubiquitously expressed Na+/H+ exchanger isoform 1 (NHE1) is
      thought to be a primary regulator of pH homeostasis, cell volume regulation, and
      the proliferative response to growth factor stimulation. To study the function of
      NHE1 during embryogenesis when these cellular processes are very active, we
      targeted the Nhe1 gene by replacing the sequence encoding transmembrane domains 6
      and 7 with the neomycin resistance gene. NHE activity assays on isolated acinar
      cells indicated that the targeted allele is functionally null. Although the
      absence of NHE1 is compatible with embryogenesis, Nhe1 homozygous mutants (-/-)
      exhibit a decreased rate of postnatal growth that is first evident at 2 wk of
      age. At this time, Nhe1 -/- animals also begin to exhibit ataxia and epileptic
      like seizures. Approximately 67% of the -/- mutants die before weaning.
      Postmortem examinations frequently revealed an accumulation of a waxy particulate
      material inside the ears, around the eyes and chin, and on the ventral surface of
      the paws. Histological analysis of adult tissues revealed a thickening of the
      lamina propria and a slightly atrophic glandular mucosa in the stomach.

PMID- 10199809
TI  - Ca2+-ATPases and their expression in the mammary gland of pregnant and lactating
      rats.
AB  - The transcellular Ca2+ fluxes required for milk production must be rigorously
      regulated to maintain the low cytosolic Ca2+ concentrations critical to cell
      function. Ca2+-ATPases play a critical role in the maintenance of this cellular
      Ca2+ homeostasis. Using RT-PCR and sequencing, we identified six Ca2+ pumps in
      lactating mammary tissue. Three plasma membrane Ca2+-ATPases (PMCAs) were found
      (PMCA1b, PMCA2b, and PMCA4b). Two sarco (endo)plasmic reticulum Ca2+-ATPases
      (SERCAs) were identified (SERCA2 and SERCA3), and the rat homologue to the yeast
      Golgi Ca2+-ATPase RS-10 was also found. The pattern of mRNA expression of each of
      these pumps was examined in rat mammary tissue from the 7th day of pregnancy to
      the 21st day of lactation. Northern blots revealed increased mRNA expression for
      all Ca2+ pumps by the 14th day of lactation, and transcripts continued to
      increase through the 18th day of lactation. PMCA1b, PMCA4b, SERCA2, and SERCA3
      showed the lowest levels of expression. RS-10 transcripts were more abundant than
      SERCA2, SERCA3, PMCA1b, and PMCA4b. RS-10 was the only pump to increase in
      expression before parturition. PMCA2b was the most abundant transcript found in
      lactating mammary tissue. At peak lactation, expression of PMCA2b approached that
      of actin. The high expression, high affinity for Ca2+, and high activity at low
      calmodulin concentrations exhibited by PMCA2b suggest that it is uniquely suited
      for maintenance of Ca2+ homeostasis in the lactating mammary gland. The pattern
      of expression and abundance of RS-10 suggest that it is a candidate for the Golgi
      Ca2+-ATPase shown to be important in maintaining the Golgi Ca2+ concentration
      required for casein synthesis and micelle formation.

PMID- 10199810
TI  - Stimulation of cystine uptake by nitric oxide: regulation of endothelial cell
      glutathione levels.
AB  - Nitric oxide (NO) is known to produce some of its biological activity through
      modification of cellular thiols. Return of cellular thiols to their basal state
      requires the activity of the GSH redox cycle, suggesting important interactions
      between NO signaling and regulation of cellular redox status. Because continuous
      exposure to NO may lead to adaptive responses in cellular redox systems, we
      investigated the effects of NO on cellular GSH levels in vascular endothelial
      cells. Acute exposure (1 h) of cells to >1 mM S-nitroso-N-acetyl-penicillamine
      (SNAP) led to depletion of GSH. On the other hand, chronic exposure to lower
      concentrations of SNAP (</=1 mM) led to a progressive increase in cytosolic GSH,
      reaching fourfold above basal by 16 h. The mechanism may involve an increase in
      GSH biosynthesis through effects on biosynthetic enzymes or through increased
      supply of cysteine, the limiting substrate. In this regard, we report that
      chronic exposure to SNAP led to a concentration-dependent increase in cystine
      uptake over a time course similar to that seen for elevation of GSH. The effect
      of SNAP on cystine uptake was inhibitable by either cycloheximide or actinomycin
      D, suggesting a requirement for both RNA and protein synthesis. Furthermore,
      uptake was Na+ independent and was blocked by extracellular glutamate.
      Extracellular glutamate also blocked SNAP-mediated elevation of cytosolic GSH.
      Finally, in a coculture model, NO produced by cytokine-pretreated RAW 264.7 cells
      increased both GSH levels and cystine uptake in naive endothelial cells. These
      findings strongly suggest that NO leads to adaptive induction of the x-c amino
      acid transport system, increased cystine uptake, and elevation of intracellular
      GSH levels.

PMID- 10199811
TI  - Hypoxia induces permeability in brain microvessel endothelial cells via VEGF and
      NO.
AB  - In this study, an in vitro model of the blood-brain barrier, consisting of
      porcine brain-derived microvascular endothelial cells (BMEC), was used to
      evaluate the mechanism of hypoxia-induced hyperpermeability. We show that hypoxia
      induced permeability in BMEC was completely abolished by a neutralizing antibody
      to vascular endothelial growth factor (VEGF). In contrast, under normoxic
      conditions, addition of VEGF up to 100 ng/ml did not alter monolayer barrier
      function. Treatment with either hypoxia or VEGF under normoxic conditions induced
      a twofold increase in VEGF binding sites and VEGF receptor 1 (Flt-1) mRNA
      expression in BMEC. Hypoxia-induced permeability also was prevented by the nitric
      oxide (NO) synthase inhibitor NG-monomethyl-L-arginine, suggesting that NO is
      involved in hypoxia-induced permeability changes, which was confirmed by
      measurements of the cGMP level. During normoxia, treatment with VEGF (5 ng/ml)
      increased permeability as well as cGMP content in the presence of several
      antioxidants. These results suggest that hypoxia-induced permeability in vitro is
      mediated by the VEGF/VEGF receptor system in an autocrine manner and is
      essentially dependent on reducing conditions stabilizing the second messenger NO
      as the mediator of changes in barrier function of BMEC.

PMID- 10199812
TI  - Hormonal regulation of oligopeptide transporter pept-1 in a human intestinal cell
      line.
AB  - The intestinal oligopeptide transporter (cloned as Pept-1) has major roles in
      protein nutrition and drug therapy. A key unstudied question is whether
      expression of Pept-1 is hormonally regulated. In this experiment, we investigated
      whether insulin has such a role. We used a human intestinal cell monolayer (Caco
      2) as the in vitro model of human small intestine and glycylglutamine (Gly-Gln)
      as the model substrate for Pept-1. Results showed that addition of insulin at a
      physiological concentration (5 nM) to incubation medium greatly stimulates Gly
      Gln uptake by Caco-2 cells. This stimulation was blocked when genistein, an
      inhibitor of tyrosine kinase, was added to incubation medium. Studies of the
      mechanism of insulin stimulation showed the following. 1) Stimulation occurred
      promptly (30-60 min) after exposure to insulin. 2) There was no significant
      change in the Michaelis-Menten constant of Gly-Gln transport, but there was a
      nearly twofold increase in its maximal velocity. 3) Insulin effect persisted even
      when Golgi apparatus, which is involved in trafficking of newly synthesized Pept
      1, was dismantled. 4) However, there was complete elimination of insulin effect
      by disruption of microtubules involved in trafficking of preformed Pept-1. 5)
      Finally, with insulin treatment, there was no change in Pept-1 gene expression,
      but the amount of Pept-1 protein in the apical membrane was increased. In
      conclusion, the results show that insulin, when it binds to its receptor,
      stimulates Gly-Gln uptake by Caco-2 cells by increasing the membrane population
      of Pept-1. The mechanism appears to be increased translocation of this
      transporter from a preformed cytoplasmic pool.

PMID- 10199813
TI  - UTP inhibits Na+ absorption in wild-type and DeltaF508 CFTR-expressing human
      bronchial epithelia.
AB  - Ca2+-mediated agonists, including UTP, are being developed for therapeutic use in
      cystic fibrosis (CF) based on their ability to modulate alternative Cl-
      conductances. As CF is also characterized by hyperabsorption of Na+, we
      determined the effect of mucosal UTP on transepithelial Na+ transport in primary
      cultures of human bronchial epithelia (HBE). In symmetrical NaCl, UTP induced an
      initial increase in short-circuit current (Isc) followed by a sustained
      inhibition. To differentiate between effects on Na+ absorption and Cl- secretion,
      Isc was measured in the absence of mucosal and serosal Cl- (INa). Again, mucosal
      UTP induced an initial increase and then a sustained decrease that reduced
      amiloride-sensitive INa by 73%. The Ca2+-dependent agonists histamine,
      bradykinin, serosal UTP, and thapsigargin similarly induced sustained inhibition
      (62-84%) of INa. Mucosal UTP induced similar sustained inhibition (half-maximal
      inhibitory concentration 296 nM) of INa in primary cultures of human CF airway
      homozygous for the DeltaF508 mutation. BAPTA-AM blunted UTP-dependent inhibition
      of INa, but inhibitors of protein kinase C (PKC) and phospholipase A2 had no
      effect. Indeed, direct activation of PKC by phorbol 12-myristate 13-acetate
      failed to inhibit Na+ absorption. Apyrase, a tri- and diphosphatase, did not
      reverse inhibitory effects of UTP on INa, suggesting a long-term inhibitory
      effect of UTP that is independent of receptor occupancy. After establishment of a
      mucosa-to-serosa K+ concentration gradient and permeabilization of the mucosal
      membrane with nystatin, mucosal UTP induced an initial increase in K+ current
      followed by a sustained inhibition. We conclude that increasing cellular Ca2+
      induces a long-term inhibition of transepithelial Na+ transport across normal and
      CF HBE at least partly due to downregulation of a basolateral membrane K+
      conductance. Thus UTP may have a dual therapeutic effect in CF airway: 1)
      stimulation of a Cl- secretory response and 2) inhibition of Na+ transport.

PMID- 10199814
TI  - Shear-induced tyrosine phosphorylation in endothelial cells requires Rac1
      dependent production of ROS.
AB  - The shear-induced intracellular signal transduction pathway in vascular
      endothelial cells involves tyrosine phosphorylation and activation of mitogen
      activated protein (MAP) kinase, which may be responsible for the sustained
      release of nitric oxide. MAP kinase is known to be activated by reactive oxygen
      species (ROS), such as H2O2, in several cell types. ROS production in ligand
      stimulated nonphagocytic cells appears to require the participation of a Ras
      related small GTP-binding protein, Rac1. We hypothesized that Rac1 might serve as
      a mediator for the effect of shear stress on MAP kinase activation. Exposure of
      bovine aortic endothelial cells to laminar shear stress of 20 dyn/cm2 for 5-30
      min stimulated total cellular and cytosolic tyrosine phosphorylation as well as
      tyrosine phosphorylation of MAP kinase. Treating endothelial cells with the
      antioxidants N-acetylcysteine and pyrrolidine dithiocarbamate inhibited in a dose
      dependent manner the shear-stimulated increase in total cytosolic and,
      specifically, MAP kinase tyrosine phosphorylation. Hence, the onset of shear
      stress caused an enhanced generation of intracellular ROS, as evidenced by an
      oxidized protein detection kit, which were required for the shear-induced total
      cellular and MAP kinase tyrosine phosphorylation. Total cellular and MAP kinase
      tyrosine phosphorylation was completely blocked in sheared bovine aortic
      endothelial cells expressing a dominant negative Rac1 gene product (N17rac1). We
      concluded that the GTPase Rac1 mediates the shear-induced tyrosine
      phosphorylation of MAP kinase via regulation of the flow-dependent redox changes
      in endothelial cells in physiological and pathological circumstances.

PMID- 10199815
TI  - TGF-alpha reduces bradykinin-stimulated ion transport and prostaglandin release
      in human colonic epithelial cells.
AB  - The effect of chronic exposure to transforming growth factor-alpha (TGF-alpha) on
      bradykinin-stimulated acute prostanoid production and ion secretion in monolayers
      of HCA-7 colony 29 colonic epithelial cells has been studied. Monolayers
      synthesized prostaglandin E2 (PGE2) at a basal rate of 2.10 +/- 0.31 pg.
      monolayer-1. min-1 over 24 h. Bradykinin (10(-8)-10(-5) M) dose dependently
      increased acute PGE2 release by three orders of magnitude. This was associated
      with a rise in cAMP from 1.60 +/- 0.14 to 2.90 +/- 0.1 pmol/monolayer (P < 0.02)
      and a dose-dependent increase in short-circuit current (SCC). When monolayers
      were primed by a 24-h exposure to TGF-alpha, basal PGE2 release rose to 6.31 +/-
      0.38 pg. monolayer-1. min-1 (TGF-alpha concn 10 ng/ml; P = 0.001). However, the
      stimulation of acute prostaglandin release, intracellular cAMP, and increased SCC
      by bradykinin was significantly reduced by preincubation with TGF-alpha. Priming
      with PGE2 (10(-8)-10(-6) M) over 24 h mimicked the effect of TGF-alpha on
      bradykinin-induced changes in cAMP and SCC. These data suggest that enhanced
      chronic release of prostaglandins in response to stimulation with TGF-alpha may
      downregulate acute responses to bradykinin. In vivo, TGF-alpha could have an
      important modulatory function in regulating secretion under inflammatory
      conditions.

PMID- 10199816
TI  - Effect of selective proteasome inhibitors on TNF-induced activation of primary
      and transformed endothelial cells.
AB  - The objective of this study was to assess the effects of two structurally
      distinct yet selective proteasome inhibitors (PS-341 and lactacystin) on
      leukocyte adhesion, endothelial cell adhesion molecule (ECAM) expression, and
      nuclear factor-kappaB (NF-kappaB) activation in tumor necrosis factor (TNF)-alpha
      stimulated human umbilical vein endothelial cells (HUVEC) and the transformed,
      HUVEC-derived, ECV cell line. We found that TNF (10 ng/ml) significantly enhanced
      U-937 and polymorphonuclear neutrophil (PMN) adhesion to HUVEC but not to ECV;
      TNF also significantly enhanced surface expression of vascular cell adhesion
      molecule 1 and E-selectin (in HUVEC only), as well as intercellular adhesion
      molecule 1 (ICAM-1; in HUVEC and ECV). Pretreatment of HUVEC with lactacystin
      completely blocked TNF-stimulated PMN adhesion, partially blocked U-937 adhesion,
      and completely blocked TNF-stimulated ECAM expression. Lactacystin attenuated TNF
      stimulated ICAM-1 expression in ECV. Pretreatment of HUVEC with PS-341 partially
      blocked TNF-stimulated leukocyte adhesion and ECAM expression. These effects of
      lactacystin and PS-341 were associated with inhibitory effects on TNF-stimulated
      NF-kappaB activation in both HUVEC and ECV. Our results demonstrate the
      importance of the 26S proteasome in TNF-induced activation of NF-kappaB, ECAM
      expression, and leukocyte-endothelial adhesive interactions in vitro.

PMID- 10199817
TI  - Amino acids are compatible osmolytes for volume recovery after hypertonic
      shrinkage in vascular endothelial cells.
AB  - The response to chronic hypertonic stress has been studied in human endothelial
      cells derived from saphenous veins. In complete growth medium the full recovery
      of cell volume requires several hours and is neither associated with an increase
      in cell K+ nor hindered by bumetanide but depends on an increased intracellular
      pool of amino acids. The highest increase is exhibited by neutral amino acid
      substrates of transport system A, such as glutamine and proline, and by the
      anionic amino acid glutamate. Transport system A is markedly stimulated on
      hypertonic stress, with an increase in activity roughly proportional to the
      extent and the duration of the osmotic shrinkage. Cycloheximide prevents the
      increase in transport activity of system A and the recovery of cell volume. It is
      concluded that human endothelial cells counteract hypertonic stress through the
      stimulation of transport system A and the consequent expansion of the
      intracellular amino acid pool.

PMID- 10199818
TI  - NHE2 contains subdomains in the COOH terminus for growth factor and protein
      kinase regulation.
AB  - The cloned epithelial cell-specific Na+/H+ exchanger (NHE) isoform NHE2 is
      stimulated by fibroblast growth factor (FGF), phorbol 12-myristate 13-acetate
      (PMA), okadaic acid (OA), and fetal bovine serum (FBS) through a change in
      maximal velocity of the transporter. In the present study, we used COOH-terminal
      truncation mutants to delineate specific domains in the COOH terminus of NHE2
      that are responsible for growth factor and/or protein kinase regulation. Five
      truncation mutants (designated by the amino acid number at the truncation site)
      were stably expressed in NHE-deficient PS120 fibroblasts. The effects of PMA,
      FGF, OA, FBS, and W-13 [a Ca2+/calmodulin (CaM) inhibitor] were studied.
      Truncation mutant E2/660, but not E2/573, was stimulated by PMA. OA stimulated
      E2/573 but not E2/540. FGF stimulated E2/540 but not E2/499. The most truncated
      mutant, E2/499, was stimulated by FBS. W-13 stimulated the basal activity of the
      wild-type NHE2. However, W-13 had no effect on E2/755. By monitoring the emission
      spectra of dansylated CaM fluorescence, we showed that dansylated CaM bound
      directly to a purified fusion protein of glutathione S-transferase and the last
      87 amino acids of NHE2 in a Ca2+-dependent manner, with a stoichiometry of 1:1
      and a dissociation constant of 300 nM. Our results showed that the COOH terminus
      of NHE2 is organized into separate stimulatory and inhibitory growth
      factor/protein kinase regulatory subdomains. This organization of growth
      factor/protein kinase regulatory subdomains is very similar to that of NHE3,
      suggesting that the tertiary structures of the putative COOH termini of NHE2 and
      NHE3 are very similar despite the minimal amino acid identity in this part of the
      two proteins.

PMID- 10199819
TI  - In vivo regulation of beta-MHC gene in rodent heart: role of T3 and evidence for
      an upstream enhancer.
AB  - Cardiac beta-myosin heavy chain (beta-MHC) gene expression is mainly regulated
      through transcriptional processes. Although these results are based primarily on
      in vitro cell culture models, relatively little information is available
      concerning the interaction of key regulatory factors thought to modulate MHC
      expression in the intact rodent heart. Using a direct gene transfer approach, we
      studied the in vivo transcriptional activity of different-length beta-MHC
      promoter fragments in normal control and in altered thyroid states. The test beta
      MHC promoter was fused to a firefly luciferase reporter gene, whereas the control
      alpha-MHC promoter was fused to the Renilla luciferase reporter gene and was used
      to account for variations in transfection efficiency. Absolute reporter gene
      activities showed that beta- and alpha-MHC genes were individually and
      reciprocally regulated by thyroid hormone. The beta-to-alpha ratios of reporter
      gene expression demonstrated an almost threefold larger beta-MHC gene expression
      in the longest than in the shorter promoter fragments in normal control animals,
      implying the existence of an upstream enhancer. A mutation in the putative
      thyroid response element of the -408-bp beta-MHC promoter construct caused
      transcriptional activity to drop to null. When studied in the -3, 500-bp beta-MHC
      promoter, construct activity was reduced ( approximately 100-fold) while thyroid
      hormone responsiveness was retained. These findings suggest that, even though the
      bulk of the thyroid hormone responsiveness of the gene is contained within the
      first 215 bp of the beta-MHC promoter sequence, the exact mechanism of
      triiodothyronine (T3) action remains to be elucidated.

PMID- 10199820
TI  - Regulation of intracellular polyamine biosynthesis and transport by NO and
      cytokines TNF-alpha and IFN-gamma.
AB  - Nitric oxide (NO) has been described to exert cytostatic effects on cellular
      proliferation; however the mechanisms responsible for these effects have yet to
      be fully resolved. Polyamines, conversely, are required components of cellular
      proliferation. In experimental models of inflammation, a relationship between
      these two pathways has been suggested by the temporal regulation of a common
      precursor, arginine. This study was undertaken to determine the effects NO and
      the NO synthase (NOS)-inducing cytokines, tumor necrosis factor-alpha (TNF-alpha)
      and interferon-gamma (IFN-gamma), exert on polyamine regulation. The transformed
      kidney proximal tubule cell line, MCT, maintains high constitutive levels of the
      first polyamine biosynthetic enzyme, ornithine decarboxylase (ODC). NO donors
      markedly suppressed ODC activity in MCT and all other cell lines examined. TNF
      alpha and IFN-gamma induction of NO generation resulted in suppressed ODC
      activity, an effect prevented by the inducible NOS inhibitor L-N6-(1
      iminoethyl)lysine (L-NIL). Dithiothreitol reversal of NO-mediated ODC suppression
      supports nitrosylation as the mechanism of inactivation. We also evaluated
      polyamine uptake, inasmuch as inhibition of ODC can result in a compensatory
      induction of polyamine transporters. Administration of NO donors, or TNF-alpha
      and IFN-gamma, suppressed [3H]putrescine uptake, thereby preventing transport
      mediated reestablishment of intracellular polyamine levels. This study
      demonstrates the capacity of NO and inflammatory cytokines to regulate both
      polyamine biosynthesis and transport.

PMID- 10199821
TI  - Muscle LIM protein: expressed in slow muscle and induced in fast muscle by
      enhanced contractile activity.
AB  - To identify early changes in gene expression during the fast-to-slow transition
      induced by chronic low-frequency stimulation, total RNA was extracted from 12-h
      stimulated tibialis anterior (TA) muscles of rats and amplified by differential
      display RT-PCR. Among the signals of differentially expressed mRNAs, a cDNA
      approximately 300 bp in length, which was almost undetectable in control TA
      muscles but prominent in stimulated TA and normal soleus muscles, was identified.
      This cDNA was cloned and identified as corresponding to the mRNA of the muscle
      LIM protein (MLP). Its differential expression in control, stimulated TA, and
      soleus muscles was verified by Northern blotting. Antibodies against MLP were
      used to identify by immunoblot analysis a protein of 22 kDa, the predicted
      molecular mass of MLP. Immunohistochemistry revealed strong reactivity for MLP in
      all fibers of normal soleus muscle and faint staining of some type IIA and type I
      fibers in control TA muscle. These fibers increased in number and staining
      intensity in 4-day-stimulated TA muscle. MLP thus seems to play an essential role
      during the rearrangement of cytoskeletal and/or myofibrillar structures in
      transforming adult muscle fibers.

PMID- 10199822
TI  - Purinergic and cholinergic agonists induce exocytosis from the same granule pool
      in HT29-Cl.16E monolayers.
AB  - Several secretagogues induce mucin secretion in epithelial monolayers, as
      determined by measuring released granule contents. To assess whether different
      agonists act on the same granule pool, capacitance changes in intact monolayers
      of the goblet cell line HT29-Cl.16E were measured by a novel impedance method.
      Apical ATP (purinergic agonist) and basolateral carbachol (cholinergic agonist)
      induce rapid exocytosis with maximal capacitance changes within 3 min. The
      maximal levels of exocytosis that can be induced by optimal concentrations of
      either agonist are the same and produce a 30-40% increase in total monolayer
      capacitance. When ATP and carbachol are applied simultaneously, the magnitude of
      exocytosis is unchanged from the single-secretagogue level. The recovery of
      capacitance to baseline (endocytosis) is significantly faster after ATP
      stimulation than after carbachol stimulation. When ATP and carbachol are applied
      sequentially at doses that give maximal exocytosis, the magnitude of the
      capacitance increase produced by the second secretagogue is less than or equal to
      that of the capacitance decrease during the recovery period. Together, these data
      suggest that purinergic and cholinergic agonists act on the same granule pool.

PMID- 10199823
TI  - Caffeine does not inhibit substance P-evoked intracellular Ca2+ mobilization in
      rat salivary acinar cells.
AB  - We used the Ca2+-sensitive fluorescent dye fura 2, together with measurements of
      intracellular D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3], to assess the
      inhibitory effects of caffeine on signal transduction via G protein-coupled
      receptor pathways in isolated rat mandibular salivary acinar cells. ACh,
      norepinephrine (NE), and substance P (SP) all evoked substantial increases in the
      intracellular free Ca2+ concentration ([Ca2+]i). Responses to ACh and NE were
      markedly inhibited by prior application of 20 mM caffeine. The inhibitory effect
      of caffeine was not reproduced by phosphodiesterase inhibition with IBMX or
      addition of cell-permeant dibutyryl cAMP. In contrast to the ACh and NE
      responses, the [Ca2+]i response to SP was unaffected by caffeine. Despite this,
      SP and ACh appeared to mobilize Ca2+ from a common intracellular pool.
      Measurements of agonist-induced changes in Ins(1,4,5)P3 levels confirmed that
      caffeine inhibited the stimulus-response coupling pathway at a point before
      Ins(1,4,5)P3 generation. Caffeine did not, however, inhibit [Ca2+]i responses
      evoked by direct activation of G proteins with 40 mM F-. These data show that
      caffeine inhibits G protein-coupled signal transduction in these cells at some
      element that is common to the muscarinic and alpha-adrenergic signaling pathways
      but is not shared by the SP signaling pathway. We suggest that this element might
      be a specific structural motif on the G protein-coupled muscarinic and alpha
      adrenergic receptors.

PMID- 10199824
TI  - Effects of melatonin on ionic currents in cultured ocular tissues.
AB  - The effects of melatonin on ionic conductances in a cultured mouse lens
      epithelial cell line (alpha-TN4) and in cultured human trabecular meshwork (HTM)
      cells were measured using the amphotericin perforated patch whole cell voltage
      clamp technique. Melatonin stimulated a voltage-dependent Na+-selective current
      in lens epithelial cells and trabecular meshwork cells. The effects of melatonin
      were observed at 50 pM and were maximal at 100 microM. Melatonin enhanced
      activation and inactivation kinetics, but no change was observed in the voltage
      dependence of activation. The results are consistent with an increase in the
      total number of ion channels available for activation by membrane depolarization.
      Melatonin was also found to stimulate a K+-selective current at high doses (1
      mM). Melatonin did not affect the inwardly rectifying K+ current or the delayed
      rectifier type K+ current that has been described in cultured mouse lens
      epithelial cells. The results show that melatonin specifically stimulated the TTX
      insensitive voltage-dependent Na+ current by an apparently novel mechanism.

PMID- 10199825
TI  - Endothelin-B receptors activate Galpha13.
AB  - Endothelin (ET) receptors activate heterotrimeric G proteins that are members of
      the Gi, Gq, and Gs families but may also activate members of other families such
      as Galpha12/13. Galpha13 has multiple complex cellular effects that are similar
      to those of ET. We studied the ability of ET receptors to activate Galpha13 using
      an assay for G protein alpha-chain activation that is based on the fact that an
      activated (GTP-bound) alpha-chain is resistant to trypsinization compared with an
      inactive (GDP-bound) alpha-chain. Nonhydrolyzable guanine nucleotides and AlMgF
      protected Galpha13 from degradation by trypsin. In membranes from human embryonic
      kidney 293 cells that coexpress ETB receptors and alpha13, ET-3 and 5'
      guanylylimidodiphosphate [Gpp(NH)p] increased the protection of alpha13 compared
      with Gpp(NH)p alone. The specificity of ETB receptor-alpha13 coupling was
      documented by showing that beta2 receptors and isoproterenol or ETA receptors and
      ET-1 did not activate alpha13 and that a specific antagonist for ETB receptors
      blocked ET-3-dependent activation of alpha13.

PMID- 10199826
TI  - ETB receptor activation leads to activation and phosphorylation of NHE3.
AB  - In OKP cells expressing ETB endothelin receptors, activation of Na+/H+ antiporter
      activity by endothelin-1 (ET-1) was resistant to low concentrations of
      ethylisopropyl amiloride, indicating regulation of Na+/H+ exchanger isoform 3
      (NHE3). ET-1 increased NHE3 phosphorylation in cells expressing ETB receptors but
      not in cells expressing ETA receptors. Receptor specificity was not due to
      demonstrable differences in receptor-specific activation of tyrosine
      phosphorylation pathways or inhibition of adenylyl cyclase. Phosphorylation was
      associated with a decrease in mobility on SDS-PAGE, which was reversed by
      treating immunoprecipitated NHE3 with alkaline phosphatase. Phosphorylation was
      first seen at 5 min and was maximal at 15-30 min. Phosphorylation was maximal
      with 10(-9) M ET-1. Phosphorylation occurred on threonine and serine residues at
      multiple sites. In summary, ET-1 induces NHE3 phosphorylation in OKP cells on
      multiple threonine and serine residues. ETB receptor specificity, time course,
      and concentration dependence are all similar between ET-1-induced increases in
      NHE3 activity and phosphorylation, suggesting that phosphorylation plays a key
      role in activation.

PMID- 10199828
TI  - Organic cation transport in rat choroid plexus cells studied by fluorescence
      microscopy.
AB  - Quinacrine uptake and distribution were studied in a primary culture of rat
      choroid plexus epithelial cells using conventional and confocal fluorescence
      microscopy and image analysis. Quinacrine rapidly accumulated in cells, with
      steady-state levels being achieved after 10-20 min. Uptake was reduced by other
      organic cations, e.g., tetraethylammonium (TEA), and by KCN. Quinacrine
      fluorescence was distributed in two cytoplasmic compartments, one diffuse and the
      other punctate. TEA efflux experiments indicated that more than one-half of
      intracellular organic cation was in a slowly emptying compartment. The
      protonophore monensin both emptied that TEA compartment and abolished punctate
      quinacrine fluorescence, suggesting that a large fraction of total intracellular
      organic cation was sequestered in acidic vesicles, e.g., endosomes. Finally,
      quinacrine-loaded vesicles were seen to move within the cytoplasm and to abruptly
      release their contents at the blood side of the cell; the rate of release was
      greatly reduced by the microtubule disrupter nocodazole.

PMID- 10199827
TI  - Inhibition of polyamine synthesis induces p53 gene expression but not apoptosis.
AB  - The nuclear phosphoprotein p53 acts as a transcription factor and is involved in
      growth inhibition and apoptosis. The present study was designed to examine the
      effect of decreasing cellular polyamines on p53 gene expression and apoptosis in
      small intestinal epithelial (IEC-6) cells. Cells were grown in DMEM containing 5%
      dialyzed fetal bovine serum in the presence or absence of alpha
      difluoromethylornithine (DFMO), a specific inhibitor of polyamine biosynthesis,
      for 4, 6, and 12 days. The cellular polyamines putrescine, spermidine, and
      spermine in DFMO-treated cells decreased dramatically at 4 days and remained
      depleted thereafter. Polyamine depletion by DFMO was accompanied by a significant
      increase in expression of the p53 gene. The p53 mRNA levels increased 4 days
      after exposure to DFMO, and the maximum increases occurred at 6 and 12 days after
      exposure. Increased levels of p53 mRNA in DFMO-treated cells were paralleled by
      increases in p53 protein. Polyamines given together with DFMO completely
      prevented increased expression of the p53 gene. Increased expression of the p53
      gene in DFMO-treated cells was associated with a significant increase in G1 phase
      growth arrest. In contrast, no features of programmmed cell death were identified
      after polyamine depletion: no internucleosomal DNA fragmentation was observed,
      and no morphological features of apoptosis were evident in cells exposed to DFMO
      for 4, 6, and 12 days. These results indicate that 1) decreasing cellular
      polyamines increases expression of the p53 gene and 2) activation of p53 gene
      expression after polyamine depletion does not induce apoptosis in intestinal
      crypt cells. These findings suggest that increased expression of the p53 gene may
      play an important role in growth inhibition caused by polyamine depletion.

PMID- 10199829
TI  - Cloning of Trp1beta isoform from rat brain: immunodetection and localization of
      the endogenous Trp1 protein.
AB  - The Trp gene product has been proposed as a candidate protein for the store
      operated Ca2+ channel, but the Trp protein(s) has not been identified in any
      nonexcitable cell. We report here the cloning of a rat brain Trp1beta cDNA and
      detection and immunolocalization of the endogenous and expressed Trp1 protein. A
      400-bp product, with >95% homology to mouse Trp1, was amplified from rat
      submandibular gland RNA. Rat-specific primers were used for cloning of a full
      length rat brain Trp1beta cDNA (rTrp1), encoding a protein of 759 amino acids.
      Northern blot analysis demonstrated the transcript in several rat and mouse
      tissues. The peptide (amino acids 523-536) was used to generate a polyclonal
      antiserum. The affinity-purified antibody 1) immunoprecipitated human Trp1
      (hTrp1) from transfected HEK-293 cells, 2) reacted with a protein of
      approximately 92 kDa, but not with hTrp3, in membranes of hTrp3-expressing HEK
      293 cells, and 3) reacted with proteins of 92 and 56 kDa in human and rat brain
      membranes. Confocal microscopy and cell fractionation demonstrated that
      endogenous and expressed hTrp1 and expressed hTrp3 proteins were localized in the
      plasma membrane of HEK-293 cells, consistent with their proposed role in Ca2+
      influx. The data demonstrate for the first time the presence of Trp1 protein in a
      nonexcitable cell.

PMID- 10199830
TI  - Switched single-electrode voltage-clamp amplifiers allow precise measurement of
      gap junction conductance.
AB  - Measurement of gap junction conductance (gj) with patch-clamp amplifiers can, due
      to series resistance problems, be subject to considerable errors when large
      currents are measured. Formulas developed to correct for these errors
      unfortunately depend on exact estimates of series resistance, which are not
      always easy to obtain. Discontinuous single-electrode voltage-clamp amplifiers
      (DSEVCs) were shown to overcome series resistance problems in single whole cell
      recording. With the use of two synchronized DSEVCs, the simulated gj in a model
      circuit can be measured with a maximum error of <5% in all recording situations
      investigated (series resistance, 5-47 MOmega; membrane resistance, 20-1,000
      MOmega; gj, 1-100 nS). At a very low gj of 100 pS, the error sometimes exceeded
      5% (maximum of 15%), but the error was always <5% when membrane resistance was
      >100 MOmega. The precision of the measurements is independent of series
      resistance, membrane resistance, and gj. Consequently, it is possible to
      calculate gj directly from Ohm's law, i.e., without using correction formulas.
      Our results suggest that DSEVCs should be used to measure gj if large currents
      must be recorded, i.e., if cells are well coupled or if membrane resistance is
      low.

PMID- 10199831
TI  - LXA4, aspirin-triggered 15-epi-LXA4, and their analogs selectively downregulate
      PMN azurophilic degranulation.
AB  - The eicosanoid lipoxin A4 (LXA4) is biosynthesized in vivo by cells present at
      inflammatory sites and appears to be an endogenous anti-inflammatory mediator.
      Further, in the presence of aspirin, the 15-epimer of LXA4 (15-epi-LXA4) is
      biosynthesized and may mediate some of aspirin's desirable bioactions. LXA4, 15
      epi-LXA4, and their stable analogs inhibit inflammation in established animal
      models, indicating that these compounds may be useful for treating inflammatory
      disease states. To investigate the cellular mechanisms by which these lipid
      mediators downregulate inflammation, we investigated whether these eicosanoids
      could influence receptor-mediated degranulation of human neutrophils, an event
      thought to play a major causative role in several inflammatory disease states.
      LXA4, 15-epi-LXA4, and their stable analogs potently (IC50 < 1 nM) and
      selectively downregulated neutrophil release of azurophilic granule contents but
      did not affect other neutrophil secretory functions. Thus the cellular basis of
      action of these natural off-switches to inflammation appears to involve
      downregulation of neutrophil azurophilic granule release.

PMID- 10199832
TI  - Beneficial effect of myocardial angiogenesis on cardiac remodeling process by
      amlodipine and MCI-154.
AB  - The present study examined the effect of long-term treatment with amlodipine and
      MCI-154 (a Ca2+ sensitizer) on progressive cardiac dysfunction and
      microvasculature in the dilated cardiomyopathic (DCM) hamster heart. After
      treatment of DCM hamsters (Bio 53.58) with amlodipine or MCI-154 for 15 wk from
      the age of 5 wk, amlodipine and MCI-154 were found to cause an increase in left
      ventricular percent fractional shortening and decreases in left ventricular
      diastolic dimension and isovolumic relaxation time in echocardiograms (P < 0.01).
      A hemodynamic study showed that the diastolic time constant decreased in the
      amlodipine-treatment group (P < 0.05). In a morphometric study employing a double
      staining method that discriminated arteriolar and venular capillaries, amlodipine
      and MCI-154 caused increases in total capillary density (P < 0.05) and the
      proportion of venular capillaries (P < 0.05). Moreover, Northern blot analysis
      showed that the expression of mRNA for vascular endothelial growth factor was
      significantly increased by amlodipine and MCI-154. They preserve coronary
      microvasculature in the DCM hamster and might induce angiogenesis of small
      vessels, thereby contributing to preservation of cardiac systolic and diastolic
      function.

PMID- 10199833
TI  - Coronary microvascular protection with mg2+: effects on intracellular calcium
      regulation and vascular function.
AB  - The use of Mg2+-supplemented hyperkalemic cardioplegia preserves microvascular
      function. However, the mechanism of this beneficial action remains to be
      elucidated. We investigated the effects of Mg2+ supplementation on the regulation
      of intracellular calcium concentration ([Ca2+]i) and vascular function using an
      in vitro microvascular model. Ferret coronary arterioles (80-150 micrometer in
      diameter) were studied in a pressurized (40 mmHg) no-flow, normothermic (37
      degrees C) state. Simultaneous monitoring of internal luminal diameter and
      [Ca2+]i using fura 2 were made with microscopic image analysis. The microvessels
      (n = 6 each group) were divided into four groups according to the content of
      MgCl2 (nominally 0, 1.2, 5.0, and 25.0 mM) in a hyperkalemic cardioplegic
      solution ([K+] 25.0 mM). After baseline measurements, vessels were subjected to
      60 min of hypoxia with hyperkalemic cardioplegia (equilibrated with 95% N2-5%
      CO2) containing each concentration of Mg2+ ([Mg2+]) and were then reoxygenated.
      During hyperkalemic cardioplegia, [Ca2+]i increased in a time-dependent manner in
      all groups. In the lower [Mg2+] cardioplegia groups, [Ca2+]i was significantly
      increased at the end of the 60-min cardioplegic period (247 +/- 44 nM and 236 +/-
      49 nM in [Mg2+] 0 and 1.2 mM groups, respectively; both P < 0.05 vs. baseline)
      with 19.6-17.2% vascular contraction. Conversely, there was no significant
      [Ca2+]i increase in the higher [Mg2+] cardioplegia groups and less vascular
      contraction (5.4-4.1%, both P < 0.05 vs. [Mg2+] 1.2 mM group). After reperfusion,
      agonist (U-46619, thromboxane A2 analog)-induced vascular contraction was
      significantly enhanced in the lower [Mg2+] cardioplegia groups (both P < 0.05 vs.
      control) but was normalized in the higher [Mg2+] cardioplegia groups. Intrinsic
      myogenic contraction was significantly decreased in the lower [Mg2+] cardioplegia
      groups (both P < 0.05 vs. control) but was preserved in the higher [Mg2+]
      cardioplegia groups. These results suggest that supplementation of the solution
      with >5.0 mM [Mg2+] may prevent hyperkalemic cardioplegia-related intracellular
      Ca2+ overloading and preserve vascular contractile function in coronary
      microvessels.

PMID- 10199834
TI  - Effects of hindlimb suspension on cytosolic Ca2+ and [3H]ryanodine binding in
      cardiac myocytes.
AB  - Effects of a 14-day hindlimb suspension were examined on [3H]ryanodine binding to
      rat ventricular microsomes and on cytosolic Ca2+ concentration ([Ca2+]i) and
      voltage-dependent Ca2+ channels in isolated ventricular myocytes. In suspended
      rats, the amplitude of the twitch [Ca2+]i transient was increased without
      significant modifications of the basal [Ca2+]i and sarcoplasmic reticulum
      content. Because cell capacitance, L-type Ca2+-current density, and Ca2+-channel
      gating were not significantly modified after suspension, the increase in [Ca2+]i
      was expected to reside in a change in ryanodine receptors. Scatchard analysis of
      [3H]ryanodine binding revealed that suspension enhanced binding by increasing the
      affinity of the receptors for [3H]ryanodine without affecting the maximal binding
      capacity. Both Ca2+-release channel activity and [3H]ryanodine binding are
      modulated by Ca2+. However, the Ca2+ sensitivity of [3H]ryanodine binding
      remained unchanged after suspension. Taken together, these results suggest that
      the increase in twitch [Ca2+]i transients after suspension may result from a
      change in the intrinsic properties of the ryanodine receptors but not from a
      change in the expression level of these receptors.

PMID- 10199835
TI  - Betamethasone-mediated vascular dysfunction and changes in hematological profile
      in the ovine fetus.
AB  - Glucocorticoid administration to fetal sheep induces a sustained systemic blood
      pressure rise and an associated increase in femoral vascular resistance. We
      utilized a small vessel myograph to compare isometric vascular responses of small
      femoral arterial branches from fetal sheep infused intravenously with either
      betamethasone or vehicle in vivo from 128 days gestation. Changes in
      hematological parameters were also determined. Betamethasone was infused for 48 h
      to produce fetal plasma betamethasone concentrations similar to those observed in
      human fetuses after maternal treatment with betamethasone to accelerate fetal
      lung maturation. When compared with vessels removed from vehicle-infused fetuses,
      vessels obtained from betamethasone-treated fetuses exhibited 1) enhanced
      sensitivity to depolarizing potassium solutions; 2) no differences in response to
      the thromboxane mimetic U-46619 or norepinephrine; and 3) differential responses
      to vasodilators, enhanced sensitivity to ACh, but decreased response to
      bradykinin and forskolin. In addition, erythrocyte and leukocyte counts were
      increased in betamethasone-infused fetuses. These observations indicate that
      multiple mechanisms operate to increase fetal vascular resistance during
      antenatal betamethasone exposure.

PMID- 10199836
TI  - Distinct scavenger receptor expression and function in the human CD14(+)/CD16(+)
      monocyte subset.
AB  - The CD14(+)/CD16(+) subset of human blood monocytes, which expresses low levels
      of the lipopolysaccharide receptor CD14 and high levels of the Fc receptor CD16
      and exhibits features of mature tissue macrophages, is expanded in certain
      inflammatory conditions and may be relevant in atherosclerosis. Scavenger
      receptors (ScR) are important for lipid accumulation into macrophage-derived foam
      cells in atherogenesis and for the clearance of pathogens. Hence, we compared the
      function and expression of ScR in CD33(low) CD16(+) and CD33(high) CD14(++)
      monocyte subsets. Double immunofluorescence analysis of isolated monocytes
      revealed that the CD33(low) subset showed lower specific, ScR-mediated binding of
      DiI-labeled modified low-density lipoproteins (LDL) than CD33(high) cells.
      Differences in modified LDL binding between subsets were accompanied by changes
      in mRNA expression. RT-PCR in sorted cells indicated lower ScR class A type I/II
      (ScR-AI/II) mRNA levels in CD14(+)/CD16(+) than in CD14(++) cells, whereas CD36
      transcripts were unaltered. This was paralleled by findings in mostly CD16(+)
      monocyte-derived macrophages showing a marked reduction in ScR-mediated binding
      of acetylated LDL, but not in the binding of oxidized LDL, and lower expression
      of ScR-AI/II mRNA, but not CD36 transcripts, after exposure to tumor necrosis
      factor-alpha for 48 h in vitro. Thus the subset of CD14(+)/CD16(+) monocytes
      shows distinct ScR function and expression, possibly reflecting a preactivation
      by cytokines with a predilection for specific inflammatory or vascular
      conditions, e.g., atherogenesis.

PMID- 10199837
TI  - On the validity of blood flow measurement using colored microspheres.
AB  - The aim of this study was 1) to investigate the validity of repeated estimations
      of blood flow using colored microspheres (CMS) and 2) to develop and validate a
      method that permits four consecutive estimations in the same animal using
      nonradiolabeled microspheres (NRMS). Several mixtures of different types of
      microspheres were injected in dogs, with each mixture containing the radiolabeled
      microspheres (RMS; labeled with 113Sn) with either three CMS, four CMS, or three
      CMS and one type of fluorescent (crimson labeled) microsphere (FMS). The blood
      flows estimated with the use of any of the injected microspheres were compared
      with those measured using the RMS as the "gold standard." The results were
      analyzed by 1) regression analysis, 2) variance analysis (ANOVA I), and 3)
      estimation of the limits of agreement between RMS and NRMS flow rates. The
      results indicate that simultaneous estimations of blood flow obtained with the
      use of more than three CMS lack accuracy and reliability. A combination of three
      types of CMS with crimson-labeled FMS, however, offers the possibility to
      estimate consecutively four different flow rates in the same animal in an
      accurate way and with relatively high precision.

PMID- 10199838
TI  - Localization and quantitation of cardiac annexins II, V, and VI in hypertensive
      guinea pigs.
AB  - Annexins are characterized by Ca2+-dependent binding to phospholipids. Annexin II
      mainly participates in cell-cell adhesion and signal transduction, whereas
      annexins V and VI also seem to regulate intracellular calcium cycling. Their
      abundance and localization were determined in left ventricle (LV) and right
      ventricle (RV) from hypertensive guinea pigs, during the transition from
      compensatory hypertrophy to heart failure. Immunoblot analysis of annexins II, V,
      and VI revealed an increased accumulation (2.6-, 1.45-, and 2.3-fold,
      respectively) in LV from hypertensive guinea pigs and no modification in RV.
      Immunofluorescent labeling of annexins II, V, and VI; of Na+-K+-ATPase; and of
      sarcomeric alpha-actinin showed that in control LV and RV, 1) annexin II is
      present in nonmuscle cells; 2) annexins V and VI are mainly observed in the
      sarcolemma and intercalated disks of myocytes; 3) annexins II, V, and VI strongly
      label endothelial cells and adventitia of coronary arteries; and 4) annexin VI is
      present in the media. At the onset of heart failure, the most striking changes
      are the increased protein accumulation in LV and the very strong labeling of
      annexins II, V, and VI in interstitial tissue, suggesting a role in fibrosis
      development and cardiac remodeling.

PMID- 10199839
TI  - Altered kinetics of contraction of mouse atrial myocytes expressing ventricular
      myosin regulatory light chain.
AB  - To investigate the role of myosin regulatory light chain isoforms as a
      determinant of the kinetics of cardiac contraction, unloaded shortening velocity
      was determined by the slack-test method in skinned wild-type murine atrial cells
      and transgenic cells expressing ventricular regulatory light chain (MLC2v).
      Transgenic mice were generated using a 4.5-kb fragment of the murine alpha-myosin
      heavy chain promoter to drive high levels of MLC2v expression in the atrium.
      Velocity of unloaded shortening was determined at 15 degrees C in maximally
      activating Ca2+ solution (pCa 4.5) containing (in mmol/l) 7 EGTA, 1 free Mg2+, 4
      MgATP, 14.5 creatine phosphate, and 20 imidazole (ionic strength 180 mmol/l, pH
      7.0). Compared with the wild type (n = 10), the unloaded shortening velocity of
      MLC2v-expressing transgenic murine atrial cells (n = 10) was significantly
      greater (3.88 +/- 1.19 vs. 2.51 +/- 1.08 muscle lengths/s, P < 0.05). These
      results provide evidence that myosin light chain 2 regulates cross-bridge cycling
      rate. The faster rate of cycling in the presence of MLC2v suggests that the MLC2v
      isoform may contribute to the greater power-generating capabilities of the
      ventricle compared with the atrium.

PMID- 10199840
TI  - Phospholamban deficiency does not compromise exercise capacity.
AB  - Deficiency of phospholamban (PLB) results in enhancement of basal murine cardiac
      function and an attenuated response to beta-adrenergic stimulation. To determine
      whether the absence of PLB also reduces the reserve capacity of the murine
      cardiovascular system to respond to stress, we evaluated the heart rate (HR),
      blood pressure, and metabolic responses of PLB-deficient (PLB-/-) mice to graded
      treadmill exercise (GTE). PLB-/- mice were hypertensive at rest (125 +/- 19 vs.
      109 +/- 16 mmHg, P < 0.05) but had normal tachycardic and hypotensive responses
      to isoproterenol. The HR response to GTE was normal; however, the hypertension in
      PLB-/- mice normalized at peak exercise. Their exercise capacities, as measured
      by duration of exercise and peak oxygen consumption (VO2), were normal. The
      oxygen pulse (VO2/HR) curve was also normal in PLB-/- mice, suggesting an ability
      to appropriately increase stroke volume and oxygen extraction during GTE, despite
      an inability to increase beta-adrenergically stimulated cardiac contractility.
      Thus deficiency of PLB, although resulting in diminished beta-adrenergic
      inotropic reserve, does not compromise cardiac performance during exercise.

PMID- 10199841
TI  - BAY K 8644 modifies Ca2+ cross signaling between DHP and ryanodine receptors in
      rat ventricular myocytes.
AB  - The amplification factor of dihydropyridine (DHP)/ryanodine receptors was defined
      as the amount of Ca2+ released from the sarcoplasmic reticulum (SR) relative to
      the influx of Ca2+ through L-type Ca2+ channels in rat ventricular myocytes. The
      amplification factor showed steep voltage dependence at potentials negative to 
      10 mV but was less dependent on voltage at potentials positive to this value. In
      cells dialyzed with 0.2 mM cAMP in addition to 2 mM fura 2, the Ca2+-channel
      agonist (-)-BAY K 8644 enhanced Ca2+-channel current (ICa), shifted the
      activation curve by -10 mV, and significantly delayed its inactivation.
      Surprisingly, BAY K 8644 reduced the amplification factor by 50% at all
      potentials, even though the caffeine-releasable Ca2+ stores were mostly intact at
      holding potentials of -90 mV. In contrast, brief elevation of extracellular Ca2+
      activity from 2 to 10 mM enhanced both ICa and intracellular Ca2+ transients in
      the absence or presence of BAY K 8644 but had no significant effect on the
      amplification factor. BAY K 8644 abolished the direct dependence of the rate of
      inactivation of ICa on the release of Ca2+ from the SR. These findings suggest
      that the gain of the Ca2+-induced Ca2+ release in cardiac myocytes is regulated
      by the gating kinetics of cardiac L-type Ca2+ channels via local exchange of Ca2+
      signals between DHP and ryanodine receptors and that BAY K 8644 suppresses the
      amplification factor through attenuation of the Ca2+-dependent inactivation of
      Ca2+ channels.

PMID- 10199842
TI  - Hemodilution, cerebral O2 delivery, and cerebral blood flow: a study using
      hyperbaric oxygenation.
AB  - Hemodilution reduces blood viscosity and O2 content (CaO2) and increases cerebral
      blood flow (CBF). Viscosity and CaO2 may contribute to increasing CBF after
      hemodilution. However, because hematocrit is the major contributor to blood
      viscosity and CaO2, it has been difficult to assess their relative importance. By
      varying blood viscosity without changing CaO2, prior investigation in hemodiluted
      animals has suggested that both factors play roughly equal roles. To further
      investigate the relationship of hemodilution, blood viscosity, CaO2, and CBF, we
      took the opposite approach in hemodiluted animals, i.e., we varied CaO2 without
      changing blood viscosity. Hyperbaric O2 was used to restore CaO2 to normal after
      hemodilution. Pentobarbital sodium-anesthetized rats underwent isovolumic
      hemodilution with 6% hetastarch, and forebrain CBF was measured with
      [3H]nicotine. One group of animals did not undergo hemodilution and served as
      controls (Con). In the three experimental groups, hematocrit was reduced from 44%
      to 17-19%. Con and hemodiluted (HDil) groups were ventilated with 40% O2 at 101
      kPa (1 atmosphere absolute), which resulted in CaO2 values of 19.7 +/- 1.3 and
      8.1 +/- 0.7 (SD) ml O2/dl, respectively. A second group of hemodiluted animals
      (HBar) was ventilated with 100% O2 at 506 kPa (5 atmospheres absolute) in a
      hyperbaric chamber, which restored CaO2 to an estimated 18.5 +/- 0.5 ml O2/dl by
      increasing dissolved O2. A fourth group of hemodiluted animals (HCon) served as
      hyperbaric controls and were ventilated with 10% O2 at 506 kPa, resulting in CaO2
      of 9.1 +/- 0.6 ml O2/dl. CBF was 79 +/- 19 ml. 100 g-1. min-1 in the Con group
      and significantly increased to 123 +/- 9 ml. 100 g-1. min-1 in the HDil group.
      When CaO2 was restored to baseline with dissolved O2 in the HBar group, CBF
      decreased to 104 +/- 20 ml. 100 g-1. min-1. When normoxia was maintained during
      hyperbaric exposure in the HCon group, CBF was 125 +/- 18 ml. 100 g-1. min-1, a
      value indistinguishable from that in normobaric HDil animals. Our data
      demonstrate that the reduction in CaO2 after hemodilution is responsible for 40
      60% of the increase in CBF.

PMID- 10199843
TI  - Expression of endothelin-1, ETA and ETB receptors, and ECE and distribution of
      endothelin-1 in failing rat heart.
AB  - Endothelin (ET)-1 has a positive inotropic effect and induces hypertrophy in
      cardiomyocytes. We previously reported that the peptide level of ET-1 is
      increased in the failing heart of rats with chronic heart failure (CHF) and that
      treatment with an ETA-receptor antagonist greatly improves survival in rats with
      CHF. However, precise analysis for alteration of the myocardial ET system in the
      failing heart is not known. In this study, we used rats with CHF due to chronic
      myocardial infarction. Sham-operated rats served as a control. The results showed
      that the level of preproendothelin (preproET)-1 mRNA and the peptide level of ET
      1 were markedly increased in the heart of rats with CHF, whereas the expression
      of endothelin-converting enzyme (ECE)-1 mRNA in the heart did not differ between
      CHF and control rats. The intensity of ET-1 staining (ET-1-like immunoreactivity)
      in cardiomyocytes was markedly stronger in rats with CHF than in control rats,
      and the fibrotic tissues of the infarcted area were not stained. The mRNA and
      protein levels of both ETA and ETB receptors in the heart were significantly
      higher in rats with CHF than in control rats. The present study suggests that the
      increase in ET-1 peptide level in the heart of the rats with CHF originated from
      upregulation of preproET-1 mRNA, which was not attendant with the alteration of
      ECE-1 mRNA expression, and that both the ETA- and ETB-receptor systems are
      greatly accelerated in the failing heart.

PMID- 10199844
TI  - Hypoxic contraction of small pulmonary arteries from normal and endotoxemic rats:
      fundamental role of NO.
AB  - The present study was aimed at examining the role of nitric oxide (NO) in the
      hypoxic contraction of isolated small pulmonary arteries (SPA) in the rat.
      Animals were treated with either saline (sham experiments) or Escherichia coli
      lipolysaccharide [LPS, to obtain expression of the inducible NO synthase (iNOS)
      in the lung] and killed 4 h later. SPA (300- to 600-micrometer outer diameter)
      were mounted as rings in organ chambers for the recording of isometric tension,
      precontracted with PGF2alpha, and exposed to either severe (bath PO2 8 +/- 3
      mmHg) or milder (21 +/- 3 mmHg) hypoxia. In SPA from sham-treated rats,
      contractions elicited by severe hypoxia were completely suppressed by either
      endothelium removal or preincubation with an NOS inhibitor [NG-nitro-L-arginine
      methyl ester (L-NAME), 10(-3) M]. In SPA from LPS-treated rats, contractions
      elicited by severe hypoxia occurred irrespective of the presence or absence of
      endothelium and were largely suppressed by L-NAME. The milder hypoxia elicited no
      increase in vascular tone. These results indicate an essential role of NO in the
      hypoxic contractions of precontracted rat SPA. The endothelium independence of
      HPV in arteries from LPS-treated animals appears related to the extraendothelial
      expression of iNOS. The severe degree of hypoxia required to elicit any
      contraction is consistent with a mechanism of reduced NO production caused by a
      limited availability of O2 as a substrate for NOS.

PMID- 10199845
TI  - Arterial chemoreflex in conscious normotensive and hypertensive adult rats.
AB  - Evidence from human and animal studies suggests that the arterial chemoreflex may
      be exaggerated in essential hypertension. In the present study, cardiorespiratory
      responses to peripheral chemoreceptor stimulation were compared in conscious
      unrestrained spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY)
      and Sprague-Dawley (SD) rats (13-14 wk old). Chemoreceptors were stimulated by
      injections of potassium cyanide (30-125 microgram/kg iv). Chemoreceptor
      stimulation elicited a pressor response and bradycardia. The peak change in mean
      arterial pressure evoked during chemoreceptor stimulation was not significantly
      different between SH (n = 18) and WKY (n = 18) rats but was significantly smaller
      in SD rats (n = 18). An evaluation of respiratory responses to chemoreceptor
      stimulation in conscious and anesthetized rats also demonstrated no significant
      difference between SH and WKY rats, but the response of the SD rats tended to be
      smaller. These results demonstrate that differences in the arterial chemoreflex
      response of SH vs. normotensive rats are not linked to hypertension but, rather,
      to differences between rat strains.

PMID- 10199846
TI  - C-peptide induces a concentration-dependent dilation of skeletal muscle
      arterioles only in presence of insulin.
AB  - In this study we tested the hypothesis that C-peptide alone or in conjunction
      with insulin may cause a dilation of skeletal muscle arterioles. First-order
      arterioles (88 microm) isolated from rat cremaster muscles were pressurized (65
      mmHg), equilibrated in a Krebs bicarbonate-buffered solution (pH 7.4), gassed
      with 10% O2 (balance 5% CO2, 85% N2), and studied in a no-flow state. C-peptide
      administered at concentrations of 0.3, 1, 3, 10, 100, 300, and 1,000 ng/ml evoked
      arteriolar dilation that was not concentration dependent. In contrast, the
      administration of the four lower physiological concentrations of C-peptide to
      arterioles exposed to a nondilating concentration of insulin evoked a significant
      concentration-dependent increase in arteriolar diameter from 8.6 to 42.3% above
      control. The arteriolar dilation to C-peptide in the presence of insulin was
      completely inhibited by administration of NG-nitro-L-arginine (10(-4) M).
      Responses to ACh and adenosine were not enhanced when these drugs were
      administered in the presence of insulin. These results indicate that C-peptide
      has the capacity to evoke arteriolar dilation in skeletal muscle via a nitric
      oxide-mediated mechanism that appears to be enhanced by an interaction with
      insulin. Furthermore, the effects of insulin appear to be specific for C-peptide
      and are not the result of a general enhancement of endothelium-dependent or
      endothelium-independent dilation.

PMID- 10199847
TI  - Importance of PKC and tyrosine kinase in single or multiple cycles of
      preconditioning in rat hearts.
AB  - Both tyrosine kinase (TK) and protein kinase C (PKC) inhibitors have been shown
      individually to completely abolish the cardioprotective effects of ischemic
      preconditioning (IPC) in rabbits; however, blockade of both enzymes is necessary
      to totally abolish IPC in pigs. Recently, we have shown that TK inhibition
      partially attenuates the cardioprotective effect of IPC in intact rat hearts.
      Therefore, the present study was designed to test the hypothesis that inhibition
      of both TK and PKC is necessary to completely abolish IPC in the intact rat and
      that this effect is dependent on the intensity of the preconditioning stimulus.
      All animals were subjected to 30 min of coronary artery occlusion and 2 h of
      reperfusion. In series 1, multiple-cycle-induced IPC was produced via three 5-min
      occlusions interspersed with 5 min of reperfusion (3 x 5 IPC). Genistein (5
      mg/kg), a TK inhibitor infused 30 min before IPC, and chelerythrine chloride (5
      mg/kg), a PKC inhibitor infused 5 min before the prolonged ischemic insult, were
      administered alone or in combination in the absence or presence of 3 x 5 IPC. 3 x
      5 IPC produced a marked reduction in infarct size as a percentage of area at risk
      compared with control (8.0 +/- 0.8 vs. 56.1 +/- 0.8%). The effects of 3 x 5 IPC
      were partially blocked by pretreatment with genistein (34.0 +/- 2.0%) or
      chelerythrine (26.4 +/- 2.8%) alone; however, combined administration of
      genistein and chelerythrine completely abolished the effects of 3 x 5 IPC (50.7
      +/- 3.6%). In series 2, single-cycle IPC was elicited by one 5-min occlusion
      followed by 10 min of reperfusion (1 x 5 IPC). Compared with control, 1 x 5 IPC
      also significantly reduced infarct size (15.4 +/- 3.0%). Genistein or
      chelerythrine administered alone completely abolished 1 x 5 IPC-induced
      cardioprotection. These results suggest that the efficacy of TK and PKC
      inhibition to block IPC depends on the intensity of the preconditioning stimulus
      and that these kinases may work through parallel pathways.

PMID- 10199848
TI  - Osmotic shock: modulation of contractile function, pHi, and ischemic damage in
      perfused guinea pig heart.
AB  - To determine the contribution of changes in extracellular osmolarity to ischemic
      injury, isolated guinea pig hearts were perfused with hyposmotic (220 mosM) or
      hyperosmotic (380 mosM) buffer. 31P NMR spectroscopy was used to follow changes
      in intracellular pH (pHi) and energetics. Hyposmotic buffer decreased myocardial
      developed pressure by 30 +/- 2% and pHi by 0.02 +/- 0.01 unit, whereas
      hyperosmotic buffer increased myocardial developed pressure by 34 +/- 1% and pHi
      by 0.14 +/- 0.01 unit. All hearts recovered to control values on restoration of
      isosmotic (300 mosM) buffer. The hyperosmolar-induced intracellular alkalosis and
      developed pressure increase were not prevented by inhibition of Na+/H+ exchange
      with use of 1 microM HOE-642 but were abolished with use of bicarbonate-free
      buffers. After 20 min of total global ischemia, hearts perfused with hyposmotic
      buffer showed significantly greater recoveries of developed pressure,
      phosphocreatine, and ATP than control hearts, but hearts perfused with
      hyperosmotic buffer did not recover after ischemia. In conclusion, buffer
      osmolarities between 220 and 380 mosM alter myocardial pHi and developed pressure
      but are not deleterious during perfusion. However, buffer osmolarity
      significantly alters the extent of myocardial ischemic injury.

PMID- 10199849
TI  - Sympathovagal balance is major determinant of short-term blood pressure
      variability in healthy subjects.
AB  - Short-term blood pressure variability (BPV) has been suggested to provide
      important information about cardiovascular regulation. However, the background of
      BPV, its determinants, and physiological correlates have remained obscure. The
      aim of this study was to characterize physiological correlates of BPV and to
      investigate associations between BPV and neural and hormonal regulatory systems
      at rest in healthy subjects. We studied 117 healthy, normal-weight, nonsmoking
      male and female subjects aged 23-77 yr. Spectral analysis of BPV and heart rate
      variability (HRV) was performed from 5-min blood pressure (Finapres) and
      electrocardiogram recordings during controlled breathing. Baroreflex sensitivity
      (BRS) was measured using the phenylephrine method. In addition, plasma
      concentrations of norepinephrine, epinephrine, and arginine vasopressin and
      plasma renin activity were measured. We found that the ratio between the low- and
      high-frequency components of HRV, an index of cardiac sympathovagal balance,
      correlated positively with total power and very low- and low-frequency components
      of systolic and diastolic BPV and inversely with high-frequency components of
      systolic and diastolic BPV. BRS, predominantly a measure of cardiac vagal
      regulation, correlated inversely with BPV. Furthermore, age, gender, body mass
      index, and systolic blood pressure contributed to BPV. Vasoactive hormones were
      not significant correlates of BPV. We conclude that sympathovagal balance of
      cardiovascular regulation is the major determinant of BPV. Other factors
      associated with BPV are age, gender, body mass index, blood pressure, and BRS.

PMID- 10199850
TI  - Cortical NOS inhibition raises the lower limit of cerebral blood flow-arterial
      pressure autoregulation.
AB  - The maintenance of constant cerebral blood flow (CBF) as arterial blood pressure
      is reduced, commonly referred to as CBF-pressure autoregulation, is typically
      characterized by a plateau until the vasodilatory capacity is exhausted at the
      lower limit, after which flow falls linearly with pressure. We investigated the
      effect of cortical, as opposed to systemic, nitric oxide synthase (NOS)
      inhibition on the lower limit of CBF-pressure autoregulation. Forty-four Sprague
      Dawley rats were anesthetized with halothane and N2O in O2. With a closed cranial
      window placed the previous day in a ventilated and physiologically stable
      preparation, we determined the CBF using laser-Doppler flowmetry. Animals with
      low reactivity to inhaled CO2 and suffused ADP or ACh were excluded. Five
      arterial pressures from 100 to 40 mmHg were obtained with controlled hemorrhagic
      hypotension under cortical suffusion with artificial cerebrospinal fluid (aCSF)
      and then again after suffusion for 35 (n = 5) and 105 min (n = 10) with aCSF, 10(
      3) M Nomega-nitro-L-arginine (L-NNA; n = 12), or 10(-3) M Nomega-nitro-D-arginine
      (D-NNA; n = 5). An additional group (n = 7) was studied after a 105-min suffusion
      of L-NNA followed by a single blood withdrawal procedure. The lower limit of
      autoregulation was identified visually by four blinded reviewers as a change in
      the slope of the five-point plot of CBF vs. mean arterial blood pressure. The
      lower limit of 90 +/- 4.3 mmHg after 105 min of 1 mM L-NNA suffusion was
      increased compared with the value in the time-control group of 75 +/- 5.3 mmHg (P
      < 0.01; ANOVA) and the initial value of 67 +/- 3.7 mmHg (P < 0.001). The lower
      limit of 84 +/- 5.9 mmHg in seven animals with 105 min of suffusion of 1 mM L-NNA
      without previous blood withdrawal was significantly increased (P < 0.01) in
      comparison with 70 +/- 1.9 mmHg from those with just aCSF suffusion (n = 37). No
      changes in lower limit for the other agents or conditions, including 105 or 35
      min of aCSF or 35 min of L-NNA suffusion, were detected. The lack of effect on
      the lower limit with D-NNA suffusion suggests an enzymatic mechanism, and the
      lengthy L-NNA exposure of 105 min, but not 35 min, suggests inhibition of a
      diffusionally distant NOS source that mediates autoregulation. Thus cortical
      suffusion of L-NNA raises the lower limit of autoregulation, strongly suggesting
      that nitric oxide is at least one of the vasodilators active during hypotension
      as arterial pressure is reduced from normal.

PMID- 10199851
TI  - Two populations of sympathetic neurons project selectively to mesenteric artery
      or vein.
AB  - The objective of this study was to determine whether sympathetic neurons of the
      inferior mesenteric ganglion (IMG) projecting to mesenteric arteries could be
      distinguished by their localization, neurochemical phenotype, and
      electrophysiological properties from neurons projecting to mesenteric veins. In
      an in vitro intact vasculature-IMG preparation, neurons were labeled following
      intraluminal injection of Fluoro-Gold or rhodamine beads into the inferior
      mesenteric artery (IMA) or vein (IMV). The somata of neurons projecting to IMA
      were localized in the central part of the IMG, whereas those projecting to IMV
      were localized more peripherally. None of the labeled neurons was doubly labeled.
      Neuropeptide Y immunoreactivity was found in 18.9% of neurons innervating the
      IMA, but not in neurons innervating the IMV. Identified neurons were dissociated
      and characterized using whole cell patch-clamp recording. After direct soma
      depolarization, all of the labeled arterial and venous neurons were classified as
      tonic firing, compared with only 40% of unlabeled neurons; the remaining 60% of
      unlabeled neurons were phasic firing. The results indicate that IMG neurons
      projecting to mesenteric arteries are distinct from neurons projecting to
      mesenteric veins.

PMID- 10199852
TI  - Sympathovagal balance: how should we measure it?
AB  - There are complex interactions between the sympathetic and parasympathetic
      nervous system inputs to the sinus node. The concept of "sympathovagal balance"
      reflects the autonomic state resulting from the sympathetic and parasympathetic
      influences. Despite widespread usage of a variety of heart rate (HR) variability
      parameters as indexes of sympathovagal balance, no index has been validated as a
      measure of sympathovagal balance. This study evaluated the utility of HR, HR
      variability, and a new parameter termed the vagal-sympathetic effect (VSE) as
      indexes of sympathovagal balance. The ideal parameter had to satisfy the
      following criteria: 1) the index should vary similarly among subjects in response
      to different autonomic conditions; 2) the variability in the index among subjects
      exposed to the same autonomic conditions should be small; and 3) the response of
      the index to various autonomic conditions should reflect the underlying changes
      in physiological state and have a meaningful interpretation. Volunteers [8 men, 6
      women; mean age 28.5 +/- 4.8 (SD) yr] were evaluated for the effects of
      sympathetic and parasympathetic stimulation and blockade on HR and HR
      variability. VSE was defined as the ratio of the R-R interval to the intrinsic R
      R interval. VSE and R-R interval consistently changed in the expected directions
      with parasympathetic and sympathetic stimulation and blockade. A general
      linearized model was used to evaluate the response of each parameter. VSE and R-R
      interval had r2 values of 0.847 and 0.852, respectively. Natural logarithm of the
      low-frequency power had an r2 value of 0.781 with lower r2 values for all the
      other HR variability parameters. The coefficient of variation was also lowest for
      each condition tested for the VSE and the R-R interval. VSE and R-R interval best
      satisfy the criteria for the ideal index of sympathovagal balance. Because it is
      impractical under most conditions to measure the VSE as the index of
      sympathovagal balance, the most suitable index is the R-R interval.

PMID- 10199853
TI  - Estradiol modulates vascular response to melatonin in rat caudal artery.
AB  - The purpose of this study was to determine whether estrogen modulates the
      function of vascular melatonin receptors. We used the rat caudal artery and found
      that the contractile effects of melatonin were influenced by the estrous cycle,
      ovariectomy, and estrogen replacement. In arterial ring segments isolated from
      female rats, melatonin potentiated, in a concentration-dependent manner,
      contractions produced either by adrenergic nerve stimulation or by phenylephrine.
      Constrictor responses to melatonin were smaller in arteries from female rats in
      proestrus compared with other stages of the estrous cycle and after ovariectomy.
      Administration of 17beta-estradiol to ovariectomized female rats also resulted in
      decreased constriction of isolated arteries to melatonin; however, in vitro
      addition of 17beta-estradiol (10(-7) M) had no effect. In the caudal artery,
      melatonin appears to act on two receptor subtypes that mediate contraction and
      relaxation, respectively. The selective melatonin MT2-receptor antagonist 4
      phenyl-2-propionamidotetraline (4P-PDOT) enhanced constrictor responses to
      melatonin in arterial segments from intact female rats, consistent with the
      inhibition of MT2 receptor-mediated relaxation. In contrast, 4P-PDOT had no
      significant effect in arteries from ovariectomized female rats. However, when
      estradiol was replaced in vivo, the effect of 4P-PDOT on melatonin responses was
      restored. Thus circulating estradiol appears to enhance MT2 melatonin-receptor
      function in the thermoregulatory caudal artery of the female rat resulting in
      increased vasodilatation in response to melatonin.

PMID- 10199854
TI  - Inhibition of phospholipase A2 attenuates functional hyperemia in the hamster
      cremaster muscle.
AB  - Arachidonic acid (AA) is the common precursor for several vasodilatory factors
      involved in the local control of blood flow. This study was designed to determine
      the role of phospholipase A2 (PLA2) and AA release in functional hyperemia in the
      hamster cremaster muscle. The muscle was prepared for in vivo microscopy and
      subjected to electrical field stimulation for 1 min. First- and second-order
      arterioles dilated in response from a mean diameter of 66 +/- 5 to 88 +/- 7
      micrometer (n = 6). PLA2 was then inhibited with quinacrine (3 x 10(-6) M) for 60
      min. PLA2 inhibition was verified by an attenuation of thrombin-induced
      vasodilation (2 U/ml). Quinacrine had no effect on resting arteriolar diameter
      but completely abolished functional hyperemia. Quinacrine also had no effect on
      dilation induced by superfusion of the preparation with 3 x 10(-6)-10(-5) M AA,
      10(-6)-10(-4) M adenosine, or 10(-6)-10(-4) M sodium nitroprusside, ruling out
      nonspecific effects of quinacrine on smooth muscle contractility. These results
      indicate that functional hyperemia in the hamster cremaster muscle is dependent
      on PLA2 activation and the availability of AA.

PMID- 10199855
TI  - Heterogeneity of 4-aminopyridine-sensitive current in rabbit sinoatrial node
      cells.
AB  - The electrophysiological properties of sinoatrial (SA) node pacemaker cells vary
      in different regions of the node. In this study, we have investigated variation
      of the 4-aminopyridine (4-AP)-sensitive current as a function of the size (as
      measured by the cell capacitance) of SA node cells to elucidate the ionic
      mechanisms. The 10 mM 4-AP-sensitive current recorded from rabbit SA node cells
      was composed of transient and sustained components (Itrans and Isus,
      respectively). The activation and inactivation properties [activation: membrane
      potential at which conductance is half-maximally activated (Vh) = 19.3 mV, slope
      factor (k) = 15.0 mV; inactivation: Vh = -31.5 mV, k = 7.2 mV] as well as the
      density of Itrans (9.0 pA/pF on average at +50 mV) were independent of cell
      capacitance. In contrast, the density of Isus (0.97 pA/pF on average at +50 mV)
      was greater in larger cells, giving rise to a significant correlation with cell
      capacitance. The greater density of Isus in larger cells (presumably from the
      periphery) can explain the shorter action potential in the periphery of the SA
      node compared with that in the center. Thus variation of the 4-AP-sensitive
      current may be involved in regional differences in repolarization within the SA
      node.

PMID- 10199856
TI  - Effect of NO on transmural distribution of blood flow in hypertrophied left
      ventricle during exercise.
AB  - When exercise in the presence of a coronary artery stenosis results in
      subendocardial ischemia, administration of a nitric oxide (NO) donor increases
      subendocardial blood flow, whereas NO synthesis blockade worsens subendocardial
      hypoperfusion. Because left ventricular hypertrophy (LVH) is also associated with
      subendocardial hypoperfusion during exercise, this study tested the hypothesis
      that alterations of NO availability can similarly influence subendocardial blood
      flow in the hypertrophied heart. Studies were performed in seven dogs in which
      ascending aortic banding resulted in an 80% increase in LV weight. Myocardial
      blood flow was measured with microspheres during treadmill exercise that
      increased heart rates to 216 +/- 8 beats/min. During control exercise, mean
      myocardial blood flow in animals with LVH was similar to that in historic
      controls, but the ratio of subendocardial to subepicardial blood flow was lower
      in animals with hypertrophy (0.88 +/- 0.07) than in controls (1.36 +/- 0.08; P <
      0.05). Blockade of NO synthesis with NG-nitro-L-arginine (L-NNA; 1.5 mg/kg ic)
      caused no change in heart rate or LV systolic pressure during exercise.
      Furthermore, L-NNA did not worsen subendocardial hypoperfusion during exercise.
      Intracoronary infusion of nitroglycerin (0.4 microgram. kg-1. min-1) did not
      significantly alter either mean blood flow or the transmural distribution of
      perfusion during exercise in the hypertrophied hearts. Thus, unlike the
      subendocardial underperfusion that occurs when a stenosis limits coronary blood
      flow, alterations of NO availability did not alter subendocardial hypoperfusion
      in the hypertrophied hearts.

PMID- 10199857
TI  - L- and T-type voltage-gated Ca2+ currents in adrenal medulla endothelial cells.
AB  - We investigated voltage-dependent Ca2+ channels of bovine adrenal medulla
      endothelial cells with the whole cell version of the patch-clamp technique.
      Depolarization elicited an inward current that was carried by Ca2+ and was
      composed of a transient (T) current, present in all the cells tested, and a
      sustained (L) current, present in 65% of them. We separated these currents and
      measured their individual kinetic and gating properties. The activation threshold
      for T current was approximately -50 mV, and its maximum amplitude was -49.8 +/-
      4.8 pA (means +/- SE, n = 19) at 0 mV. The time constant was 10.2 +/- 1.5 ms (n =
      4) for activation and 18.4 +/- 2.8 ms (n = 4) for inactivation. The L current
      activated at -40 mV, and it reached a plateau at -20.1 +/- 2.3 pA (n = 6). Its
      activation time course was a single exponential with an activation time contant
      of 26.8 +/- 2.3 ms (n = 4). Current-voltage curves, kinetics, gating, response to
      BAY K 8644, nifedipine, amiloride, and different selectivity for Ba2+ and Ca2+
      indicated that the underlying channels for the observed currents are only of the
      T- and L-types that resemble those of the endocrine secretory cells.

PMID- 10199858
TI  - Delayed ischemic preconditioning is mediated by opening of ATP-sensitive
      potassium channels in the rabbit heart.
AB  - Cardioprotection from preconditioning reappears 24 h after the initial stimulus.
      This phenomenon is called the second window of protection (SWOP). We hypothesized
      that opening of the ATP-sensitive potassium (KATP) channel mediates the
      protective effect of SWOP. Rabbits were preconditioned (PC) with four cycles of 5
      min regional ischemia each followed by 10 min of reperfusion. Twenty-four hours
      later, the animals were subjected to sustained ischemia for 30 min followed by
      180 min of reperfusion (I/R). Glibenclamide (Glib, 0.3 mg/kg ip) or 5
      hydroxydecanoate (5-HD, 5 mg/kg iv) was used to block the KATP channel function.
      Infarct size was reduced from 41.2 +/- 2. 6% in sham-operated rabbits to 11.6 +/-
      1.0% in PC rabbits, a 71% reduction (n = 11, P < 0.01). Treatment with Glib or 5
      HD before I/R increased the infarct size to 43.4 +/- 2.6 and 37.8 +/- 1.9%,
      respectively (P < 0.01 vs. PC group, n = 12/group). Sham animals treated with
      either Glib or 5-HD had an infarct size of 39.0 +/- 3.4 and 37.8 +/- 1.5%,
      respectively, which was not different from control (40.0 +/- 3.8%) or sham (41.2
      +/- 2.6%) I/R hearts. Monophasic action potential duration (APD) at 50%
      repolarization significantly shortened by 28.7, 26.6, and 23.3% in sham animals
      during 10, 20, and 30 min of ischemia. However, no further augmentation in the
      shortening of APD was observed in PC hearts. Glib and 5-HD significantly
      suppressed ischemia-induced epicardial APD shortening, suggesting that 5-HD may
      not be a selective blocker of the mitochondrial KATP channel in vivo. We conclude
      that SWOP is mediated by a KATP channel-sensitive mechanism that may have
      occurred because of the opening of the sarcolemmal KATP channel in vivo.

PMID- 10199859
TI  - Phase-dependent heartbeat modulation by muscle contractions during dynamic
      handgrip in humans.
AB  - The influence of cardiac phase on the response of the cardiac pacemaker to
      dynamic hand contraction in eight healthy young men was studied to determine
      whether heart rate response to muscle contraction varied as a function of timing
      within the cardiac cycle. Changes in R-R interval (RRI) in response to muscle
      contraction were measured at various cardiac phases during heartbeat-synchronized
      handgrip at a rate of one contraction per two heartbeats. To extract the direct
      effect of the muscle contraction on the RRI, spontaneous slow variations and
      respiratory sinus arrhythmia were removed from the total RRI fluctuations in the
      frequency domain. Cross-correlograms between the extracted RRI fluctuations and
      muscle contraction showed that the coupling was strong when the muscle
      contraction occurred at the middle phase of the cardiac cycle. Muscle contraction
      at the systolic phase of the cardiac cycle had a tendency to produce a phase
      advance (shortening of RRI), whereas muscle contraction at the middle phase or
      later had a tendency to produce a phase delay (prolongation of RRI). The results
      showed the presence of a neuronal circuit that modulates the cardiac pacemaker
      activity depending on the timing of muscle contraction in the cardiac cycle.

PMID- 10199860
TI  - Oxygen-wasting effect of inotropy in the "virtual work model".
AB  - In the "virtual work model," left ventricular total mechanical energy (TME) is
      linearly related to myocardial oxygen consumption (MVO2). This relationship (MVO2
      TME) is supposedly independent of inotropic stimulation, vascular loading, and
      heart rate variations. We reexamined the effect of inotropic stimulation
      (dopamine) on the metabolic to mechanical energy transfer in nine open-chest
      anesthetized pigs. Left ventricular mechanical energy was calculated using TME
      (mean ejection pressure x end-diastolic volume + stroke work), TMEW (end
      diastolic volume reduced by unstressed ventricular volume), and the pressure
      volume area (PVA). A highly linear relationship between MVO2 and mechanical
      energy was found for all three indexes during control and dopamine runs (r = 0.87
      0.99). The slopes were unaltered by dopamine. y-Axis intercepts were (control vs.
      dopamine) as follows (in J. beat-1. 100 mg-1; means +/- SD): TME, 0.36 +/- 0.12
      vs. 0.61 +/- 0.30 (P < 0.02); TMEW, 0.43 +/- 0.16 vs. 0.72 +/- 0.32 (P < 0.02);
      and PVA, 0.34 +/- 0.13 vs. 0.60 +/- 0.30 (P < 0.02). We conclude that the virtual
      work model is dependent on inotropic stimulation and that new insight into
      myocardial chemomechanical coupling is not added by this concept.

PMID- 10199861
TI  - Impaired aerobic capacity in hypercholesterolemic mice: partial reversal by
      exercise training.
AB  - The present study assessed whether impaired aerobic capacity previously observed
      in hypercholesterolemic mice is reversible by exercise training. Seventy-two 8-wk
      old female C57BL/6J wild-type (+, n = 42) and apolipoprotein E-deficient (-, n =
      30) mice were assigned to the following eight interventions: normal chow,
      sedentary (E+, n = 17; E-, n = 8) or exercised (E+ex, n = 13; E-ex, n = 7) and
      high-fat chow, sedentary (E+chol, n = 6; E-chol, n = 8) or exercised (E+chol-ex,
      n = 6; E-chol-ex, n = 7). Mice were trained on a treadmill 2 x 1 h/day, 6
      days/wk, for 4 wk. Cholesterol levels correlated inversely with maximum oxygen
      uptake (r = -0.35; P < 0. 02), which was blunted in all hypercholesterolemic
      sedentary groups (all P < 0.05). Maximum oxygen uptake improved in all training
      groups but failed to match E+ex (all P < 0.05). Vascular reactivity and nitric
      oxide (NO) synthesis correlated with anaerobic threshold (r = 0.36; P < 0.025)
      and maximal distance run (r = 0.59; P < 0.007). We conclude that genetically
      induced hypercholesterolemia impairs aerobic capacity. This adverse impact of
      hypercholesterolemia on aerobic capacity may be related to its impairment of
      vascular NO synthesis and/or vascular smooth muscle sensitivity to
      nitrovasodilators. Aerobic capacity is improved to the same degree by exercise
      training in normal and genetically hypercholesterolemic mice, although there
      remains a persistent difference between these groups after training.

PMID- 10199862
TI  - Physiological doses of estradiol decrease nocturnal blood pressure in
      normotensive postmenopausal women.
AB  - The effect of a 2-mo treatment with transdermal estradiol (50 microgram/day)
      versus placebo on 24 h of blood pressure rhythm was investigated in 18
      normotensive healthy postmenopausal women. Whereas daytime blood pressure was not
      modified, nighttime blood pressure was reduced by estradiol. Estradiol magnified
      the nocturnal decrement of systolic (14.3 +/- 7.2 vs. 9.8 +/- 6.7 mmHg, P = 0.
      0033), diastolic (11.6 +/- 5.0 vs. 7.5 +/- 7.3 mmHg, P = 0.028), and mean (10.8
      +/- 5.6 vs. 7.2 +/- 4.5 mmHg, P = 0.011) blood pressure. As a consequence, the 24
      h rhythm of mean blood pressure was restored in 50% of the subjects (P = 0.045)
      in whom it was absent and was amplified in the remaining 50% of the subjects.
      Body mass index was an independent determinant of blood pressure values being
      directly related to the amplitude of the 24-h mean blood pressure rhythm (r2 =
      0.38; P = 0.0067). In normotensive postmenopausal women, physiological doses of
      estradiol amplify the nocturnal decline of blood pressure.

PMID- 10199863
TI  - Ischemic preconditioning depends on interaction between mitochondrial KATP
      channels and actin cytoskeleton.
AB  - Both mitochondrial ATP-sensitive K+ (KATP) channels and the actin cytoskeleton
      have been proposed to be end-effectors in ischemic preconditioning (PC). For
      evaluation of the participation of these proposed end effectors, rabbits
      underwent 30 min of regional ischemia and 3 h of reperfusion. PC by 5-min
      ischemia + 10-min reperfusion reduced infarct size by 60%. Diazoxide, a
      mitochondrial KATP-channel opener, administered before ischemia was protective.
      Protection was lost when diazoxide was given after onset of ischemia. Anisomycin,
      a p38/JNK activator, reduced infarct size, but protection from both diazoxide and
      anisomycin was abolished by 5-hydroxydecanoate (5-HD), an inhibitor of
      mitochondrial KATP channels. Isolated adult rabbit cardiomyocytes were subjected
      to simulated ischemia by centrifuging the cells into an oxygen-free pellet for 3
      h. PC was induced by prior pelleting for 10 min followed by resuspension for 15
      min. Osmotic fragility was assessed by adding cells to hypotonic (85 mosmol)
      Trypan blue. PC delayed the progressive increase in fragility seen in non-PC
      cells. Incubation with diazoxide or pinacidil was as protective as PC. Anisomycin
      reduced osmotic fragility, and this was reversed by 5-HD. Interestingly,
      protection by PC, diazoxide, and pinacidil could be abolished by disruption of
      the cytoskeleton by cytochalasin D. These data support a role for both
      mitochondrial KATP channels and cytoskeletal actin in protection by PC.

PMID- 10199864
TI  - COX-2 and cytosolic PLA2 mediate IL-1beta-induced cAMP production in human
      vascular smooth muscle cells.
AB  - Interleukin (IL)-1 is a potent vasodilator that causes prolonged induction of
      prostacyclin (PGI2) and cAMP synthesis in human vascular smooth muscle cells
      (HVSMC). The present study investigated IL-1 induction of PG synthetic enzymes in
      HVSMC and tested their respective roles in PGI2 and cAMP production.
      Cyclooxygenase (COX)-1 mRNA was not detectable in either control or IL-1-treated
      HVSMC, as assessed by RT-PCR. In contrast, COX-2 mRNA was detectable in control
      HVSMC, increased markedly (16-fold) after 1 h of IL-1 exposure, and increased
      further (52-fold) after 24 h. COX-2 protein levels, assessed by Western analysis,
      were increased concomitantly. HVSMC contained mRNA encoding both the secreted and
      cytosolic forms of phospholipase A2 (sPLA2 and cPLA2, respectively). IL-1
      stimulation did not affect sPLA2 mRNA levels, but cPLA2 mRNA levels increased at
      8 h, after the initial induction of PG synthesis. HVSMC constitutively expressed
      PGI2 synthase mRNA, and its levels were not affected by IL-1. A selective COX-2
      inhibitor, NS-398, reversed IL-1-induced PGI2 and cAMP production, supporting a
      role of COX-2 in mediating increased PG synthesis. IL-1-induced cAMP was also
      reversed by a selective cPLA2 inhibitor, AACOCF3, but not by thioetheramide
      phosphorylcholine, which inhibits sPLA2 preferentially over cPLA2, supporting a
      requirement for cPLA2-derived arachidonic acid in IL-1-induced PG synthesis. The
      delayed induction of cPLA2 mRNA was also attenuated by NS-398, suggesting that it
      was secondary to the initial COX-2-induced PG synthesis. Together, the results
      support the hypothesis that IL-1 induces intracellular PG synthesis in HVSMC via
      rapid upregulation of COX-2, which utilizes cPLA2-derived arachidonic acid to
      generate PG metabolites that regulate adenylate cyclase.

PMID- 10199865
TI  - Linkage analysis of glucocorticoid and beta2-adrenergic receptor genes with blood
      pressure and body mass index.
AB  - Glucocorticoids and catecholamines exert important effects on cardiovascular
      physiology and metabolism. Variants of the glucocorticoid receptor gene (GRL) and
      the beta2-adrenergic receptor gene (ADRB2) have been associated with high blood
      pressure and obesity. These genes are close on human chromosome 5q31-5q32, and we
      undertook a linkage analysis of this region in 264 families from the general
      population in relation to systolic and diastolic blood pressure, body mass index,
      weight, height, and pulse rate. All family members were genotyped at four
      microsatellite loci (D5S207, D5S210, D5S519, and D5S119) located on chromosome
      5q31-5q33.3. Using quantitative identity-by-descent sibling pair linkage
      analysis, we found that at no loci was genetic similarity associated with
      phenotypic similarity for systolic and diastolic blood pressure, body mass index,
      weight, height, or pulse rate. Although it is not possible to exclude the
      influence of specific combinations of certain GRL and ADRB2 polymorphisms, the
      absence of significant linkage in our population argues against a role for GRL or
      ADRB2 in physiological variation of blood pressure and body mass index.

PMID- 10199866
TI  - Effects of AT1-receptor blockade on progression of left ventricular dysfunction
      in dogs with heart failure.
AB  - The objective of the present study was to determine the effects of early long
      term monotherapy with the angiotensin II AT1-receptor antagonist valsartan on the
      progression of left ventricular (LV) dysfunction and remodeling in dogs with
      moderate heart failure (HF). Studies were performed in 30 dogs with moderate HF
      produced by multiple sequential intracoronary microembolizations. Embolizations
      were discontinued when LV ejection fraction was 30-40%. Two weeks after the last
      embolization, dogs were randomized to 3 mo of oral therapy with low-dose
      valsartan (400 mg twice daily, n = 10), to high-dose valsartan (800 mg twice
      daily, n = 10), or to no treatment at all (control, n = 10). Treatment with
      valsartan significantly reduced mean aortic pressure and LV end-diastolic
      pressure compared with control. In untreated dogs, LV ejection fraction decreased
      (37 +/- 1 vs. 29 +/- 1%, P = 0.001) and end-systolic volume (ESV) and end
      diastolic volume (EDV) increased (81 +/- 5 vs. 92 +/- 5 ml, P < 0.001; 51 +/- 3
      vs. 65 +/- 3 ml, P = 0.001, respectively) after 3 mo of follow-up compared with
      those levels before follow-up. In dogs treated for 3 mo with low-dose valsartan,
      ejection fraction was preserved (37 +/- 1 vs. 38 +/- 2%, pretreatment vs.
      posttreatment) as was ESV but not EDV. In dogs treated for 3 mo with high-dose
      valsartan, ejection fraction decreased (35 +/- 1 vs. 31 +/- 2%, P = 0.02) and ESV
      and EDV increased in a manner comparable to those levels in controls. Valsartan
      had no significant effects on cardiomyocyte hypertrophy or on the extent of
      interstitial fibrosis. We conclude that, for dogs with moderate HF, early long
      term therapy with the AT1-receptor blocker valsartan decreases preload and
      afterload but has only limited benefits in attenuating the progression of LV
      dysfunction and chamber remodeling.

PMID- 10199867
TI  - Bradykinin-stimulated protein synthesis by myocytes is dependent on the MAP
      kinase pathway and p70(S6K).
AB  - Bradykinin (BK) has a direct hypertrophic effect on rat ventricular
      cardiomyocytes (VCM) as defined by an increase in protein synthesis and an
      increase in atrial natriuretic peptide mRNA and secretion. In the current study,
      we have examined the dependence of BK-induced protein synthesis on activation of
      90-kDa ribosomal S6 kinase (p90(rsk)) and 70-kDa S6 kinase (p70(S6K)). Both of
      these kinases possess the ability to phosphorylate the ribosomal protein S6,
      which plays an important role in initiating mRNA translation. Stimulation of
      adult VCM with 10 microM BK increased p90(rsk) activity by 2.5 +/- 0.3-fold and
      increased p70(S6K) activity by 2.0 +/- 0.3-fold. p90(rsk) is a terminal kinase in
      the mitogen-activated protein (MAP) kinase pathway. Inhibition of MAP kinase
      kinase activation by Raf in the MAP kinase pathway with PD-098059 (25 microM)
      blocked BK-stimulated activation of p90(rsk) by 70% and unexpectedly blocked
      p70(S6K) by 72%. Rapamycin inhibited BK-stimulated p70(S6K) activity by 93% but
      had no effect on p90(rsk) activation by BK. Inhibition of the MAP kinase pathway
      and p70(S6K) with PD-098059 was paralleled by changes in protein synthesis. BK
      (10 microM) increased [3H]phenylalanine incorporation by 27 +/- 3 and 39 +/- 6%
      in cultured adult and neonatal VCM, respectively. Treatment with PD-098059 or
      rapamycin abolished the increase in protein synthesis stimulated by BK. These
      results suggest that 1) BK activates p70(S6K) and p90(rsk); 2) although both
      p70(S6K) and p90(rsk) have the potential to phosphorylate the ribosomal S6
      protein, p70(S6K) and not p90(rsk) is the predominant kinase involved in
      increasing protein synthesis by BK; and 3) p70(S6K) activation is dependent on
      stimulation of the MAP kinase pathway at a point distal to Raf.

PMID- 10199868
TI  - Muscle metaboreflex improves O2 delivery to ischemic active skeletal muscle.
AB  - Ischemia of active skeletal muscle elicits a powerful pressor response, termed
      the muscle metaboreflex. We recently reported that the muscle metaboreflex
      pressor response acts to partially restore blood flow to the ischemic active
      skeletal muscle. However, because this reflex is activated by reductions in O2
      delivery rather than blood flow per se, gain of the muscle metaboreflex as
      analyzed on the basis of blood flow alone may underestimate its true strength if
      this reflex also acts to increase arterial O2 content. In conscious dogs
      chronically instrumented to measure systemic arterial pressure, cardiac output,
      and hindlimb blood flow, we activated the muscle metaboreflex via graded, partial
      reductions in hindlimb blood flow during mild (3.2 km/h) and moderate (6.4 km/h,
      10% grade) workloads. At rest, during free-flow exercise, and with metaboreflex
      activation, we analyzed arterial blood samples for Hb concentration and O2
      content and compared muscle metaboreflex gain calculations based on the ability
      to partially restore flow with those based on the ability to partially restore O2
      delivery (blood flow x arterial O2 content). During both mild and moderate
      exercise, metaboreflex activation caused significant increases in arterial Hb
      concentration and O2 content. Metaboreflex gain quantified on the ability to
      partially restore O2 delivery was significantly greater than that based on
      restoration of blood flow during both mild and moderate workloads (0.52 +/- 0.10
      vs. 0.39 +/- 0.08, P < 0.05, and 0.61 +/- 0. 05 vs. 0.46 +/- 0.04, P < 0.05,
      respectively). We conclude that the muscle metaboreflex acts to increase both
      arterial O2 content and blood flow to ischemic muscle such that when combined, O2
      delivery is substantially increased and metaboreflex gain is greater when
      analyzed with a more integrative approach.

PMID- 10199870
TI  - Circulation online only : april 13, 1999 

PMID- 10199869
TI  - The potential clinical impact of 20 years of nitric oxide research.

PMID- 10199871
TI  - Adenovirus-mediated delivery of fas ligand inhibits intimal hyperplasia after
      balloon injury in immunologically primed animals.
AB  - BACKGROUND: Adenoviral constructs have been used for studies of injury-induced
      vascular hyperplasia in immunologically naive laboratory animals, but their
      usefulness for intra-arterial gene therapy may be limited by the prevalence of
      preexisting immunity to adenovirus in the patient population. Here, we explored
      the efficacy of adenovirus-mediated transfer of Fas ligand, a cytotoxic gene with
      immunomodulatory properties, in inhibiting injury-induced vascular lesion
      formation in both naive and immunologically primed animals. METHODS AND RESULTS:
      Lesion formation was evaluated in balloon-injured carotid arteries of naive and
      adenovirus-immunized rats that were infected with adenoviral constructs
      expressing Fas ligand (Ad-FasL), the cyclin-dependent kinase inhibitor p21 (Ad
      p21), or beta-galactosidase (Ad-betagal). In naive rats, Ad-FasL induced
      apoptosis in medial vascular smooth muscle cells and inhibited intimal
      hyperplasia by 60% relative to Ad-betagal-treated vessels (P<0.05), whereas the
      cytostatic agent Ad-p21 decreased lesion size by 58% (P<0.05). In animals
      preimmunized with an adenoviral vector containing no transgene, Ad-FasL
      significantly inhibited neointima formation (73% reduction, P<0.05), but Ad-p21
      failed to inhibit neointima formation relative to controls. Immunologically
      primed rats displayed robust T-cell infiltration in Ad-p21- and Ad-betagal
      treated vessels, but T-cell infiltration was markedly attenuated in Ad-FasL
      treated vessels. CONCLUSIONS: Our data demonstrate that adenovirus-mediated Fas
      ligand delivery can inhibit intimal hyperplasia in both immunologically primed
      and naive animals, whereas the efficacy of an adenovirus-mediated p21 delivery is
      limited to immunologically naive animals. This study documents, for the first
      time, the therapeutic efficacy of intravascular adenoviral gene transfer in
      animals with preexisting immunity to adenovirus.

PMID- 10199872
TI  - Local inhibition of tissue factor reduces the thrombogenicity of disrupted human
      atherosclerotic plaques: effects of tissue factor pathway inhibitor on plaque
      thrombogenicity under flow conditions.
AB  - BACKGROUND: Plaque disruption and subsequent thrombus formation lead to acute
      coronary syndromes and progression of atherosclerotic disease. Tissue factor (TF)
      appears to mediate plaque thrombogenicity. Tissue factor pathway inhibitor (TFPI)
      is the major physiological inhibitor of TF. This study analyzes the role of TF on
      thrombogenicity of disrupted human atherosclerotic plaques and the therapeutic
      possibilities of its specific inhibition. METHODS AND RESULTS: Human
      atherosclerotic and normal arterial segments were exposed to heparinized blood at
      flow conditions modeling medium-grade coronary stenosis in the Badimon perfusion
      chamber. The antithrombotic effects of the specific inhibition of plaque TF was
      assessed by reduction in the deposition of radiolabeled platelets and
      fibrin(ogen) and immunohistochemical analysis of perfused arteries. TF activity
      was inhibited by both recombinant TFPI and a polyclonal antibody against human
      TF. Human lipid-rich plaques were more thrombogenic than less advanced
      atherosclerotic plaques. Specific inhibition of TF activity reduced plaque
      thrombogenicity, inhibiting both platelet and fibrin(ogen) deposition (580 versus
      194 plateletsx10(6)/cm2; P<0.01, and 652 versus 172x10(12) molecules of Fg/cm2;
      P<0.05, respectively) and thrombosis (immunohistochemistry). CONCLUSIONS: This
      study documents the key role of TF activity in acute arterial thrombosis after
      atherosclerotic plaque disruption and provides evidence of the benefit of
      blocking plaque TF activity. Therefore the inhibition of the TF pathway opens a
      new therapeutic strategy in the prevention of acute coronary thrombosis after
      plaque disruption.

PMID- 10199873
TI  - Functional polymorphism in the regulatory region of gelatinase B gene in relation
      to severity of coronary atherosclerosis.
AB  - BACKGROUND: Gelatinase B, a matrix metalloproteinase that has proteolytic
      activity against connective tissue proteins, has been suggested to be important
      in the connective tissue remodeling processes associated with atherogenesis and
      plaque rupture. This study tested the hypothesis that sequence variation in the
      promoter region of the gelatinase B gene influences its expression, predisposing
      individuals carrying certain genetic variants to more severe atherosclerosis.
      METHODS AND RESULTS: Single-strand conformation polymorphism analysis was carried
      out to search the promoter region of the gene encoding gelatinase B for naturally
      occurring genetic variation. As a result, an unreported common polymorphism was
      detected, which arose from a cytosine (C) to thymidine (T) transition at position
      -1562 relative to the start of transcription. Transient transfection experiments
      and DNA-protein interaction assays indicated that the T allele had a higher
      promoter activity than the C allele, which appeared to be due to preferential
      binding of a putative transcription repressor protein to the C allelic promoter.
      A sample of 584 male patients with myocardial infarction and 645 age-matched male
      healthy control subjects were genotyped. The allele frequencies were not
      significantly different between the cases and control subjects. However, in 374
      patients with available angiographic data, 26% of those carrying 1 or 2 copies of
      the T allele had >50% stenosis in 3 coronary arteries, whereas only 15% of C/C
      homozygotes had triple-vessel disease. CONCLUSIONS: These data suggest that this
      functional genetic variation influences gelatinase B gene promoter activity in an
      allele-specific manner and has an effect on atherosclerotic phenotype.

PMID- 10199874
TI  - Endothelium-dependent and -independent perfusion reserve and the effect of L
      arginine on myocardial perfusion in patients with syndrome X.
AB  - BACKGROUND: Impaired vasodilatation capacity in patients with angina pectoris and
      a normal coronary arteriogram (syndrome X [SX]) has been reported. Most studies
      report on the response in epicardial vessels. This does not necessarily reflect
      compromised myocardial microcirculation. Lack of the NO precursor L-arginine has
      been suggested as a possible cause. METHODS AND RESULTS: Myocardial blood flow
      (MBF) was measured, using PET, at rest (MBF-rest) and during intravenous
      dipyridamole (MBF-DIP) in 25 women (mean age 53+/-7 years) with SX. Thirty
      healthy volunteers served as controls. One group (A) consisted of 15 age-matched
      female volunteers (54+/-10 years). The other control group consisted of 15 young
      healthy women (B; 24+/-5 years). In 12 SX patients, MBF-rest and MBF during cold
      pressor testing were also measured after infusion of L-arginine (6.7 g/min for 45
      minutes). The increase in MBF after cold pressor testing was similar in the SX
      group compared with controls. L-arginine did not affect MBF-rest (0.83+/-0.14
      versus 0.89+/-0.13 mL. g-1. min-1) or MBF after cold pressor test (0.95+/-0.10
      versus 1. 03+/-0.17 mL. g-1min-1). In contrast, the hyperemic response to DIP was
      blunted compared with the group A controls (1.68+/-0.49 versus 2. 34+/-0.45 mL. g
      1. min-1, P<0.05); this resulted in a significant reduction of the coronary flow
      reserve in SX patients relative to controls (2.03+/-0.53 versus 2.96+/-0.63 mL. g
      1. min-1, P<0.01). CONCLUSIONS: In patients with SX, the microcirculatory
      response to cold, reflecting the endothelium function, is normal and unaltered by
      intravenous L-arginine. This suggests preserved microcirculatory endothelial
      function. However, a markedly attenuated hyperemic flow and flow reserve after
      DIP suggest a dysfunction of the adenosine-mediated endothelium-independent
      vasodilatation at the microcirculatory level in these patients.

PMID- 10199875
TI  - Functional effects of endothelin and regulation of endothelin receptors in
      isolated human nonfailing and failing myocardium.
AB  - BACKGROUND: An activated endothelin (ET) system may be of pathophysiological
      relevance in human heart failure. We characterized the functional effects of ET
      1, ET receptors, and ET-1 peptide concentration in left ventricular myocardium
      from 10 nonfailing hearts (NF) and 27 hearts in end-stage failure due to
      idiopathic dilative cardiomyopathy (DCM). METHODS AND RESULTS: Inotropic effects
      were characterized in isolated muscle strips (1 Hz; 37 degrees C). ET-1 0.0001 to
      0.3 micromol/L significantly (P<0.05) increased twitch force by maximally 59+/
      10% in NF and by 36+/-11% in DCM (P<0.05 versus NF). Preincubation with
      propranolol 1 micromol/L and prazosin 0.1 micromol/L did not affect the response
      to ET-1, but the mixed ET receptor antagonist bosentan and the ETA receptor
      antagonist BQ-123 shifted the concentration-response curves for ET-1 rightward.
      The ETB receptor agonist sarafotoxin S6c 0.001 to 0.3 micromol/L had no
      functional effects. The inotropic response to ET-1 was not associated with
      increased intracellular Ca2+ transients, as assessed in aequorin-loaded muscle
      strips. ET receptor density (Bmax; radioligand binding) was 62.5+/-12.5 fmol/mg
      protein in NF and 122. 4+/-24.3 fmol/mg protein in DCM (P<0.05 versus NF). The
      increase in Bmax in DCM resulted from an increase in ETA receptors without change
      in ETB receptors. ET-1 peptide concentration (radioimmunoassay) was higher in DCM
      than in NF (14 447+/-2232 versus 4541+/-1340 pg/mg protein, P<0.05). CONCLUSIONS:
      ET-1 exerts inotropic effects in human myocardium through ETA receptor-mediated
      increases in myofibrillar Ca2+ responsiveness. In DCM, functional effects of ET-1
      are attenuated, but ETA receptor density and ET-1 peptide concentration are
      increased, indicating an activated local cardiac ET system and possibly a reduced
      postreceptor signaling efficiency.

PMID- 10199876
TI  - Effect of atrial natriuretic peptide on muscle sympathetic activity and its
      reflex control in human heart failure.
AB  - BACKGROUND: The purpose of this study was to determine if atrial natriuretic
      peptide (ANP) exerts a relative inhibitory effect on muscle sympathetic nerve
      activity (MSNA) at rest and during nonhypotensive lower body negative pressure
      (LBNP) in heart failure, as in healthy subjects. METHODS AND RESULTS: Fifteen men
      (age 39+/-2 years [mean+/-SE]) with dilated cardiomyopathy (ejection fraction
      18+/-3%) received intravenous ANP (50 microgram bolus, then 50 ng. kg-1. min-1)
      and nitroglycerin (NTG, 8 mg/min) as a hemodynamic control. During each infusion
      MSNA, blood pressure (BP), central venous pressure (CVP), and heart rate (HR)
      were recorded before and during LBNP at -6 and -12 mm Hg. NTG and ANP caused
      similar and significant reductions in CVP and diastolic BP, but resting MSNA did
      not increase with either infusion. LBNP at -6 mm Hg lowered CVP (P<0.05), whereas
      LBNP at -12 mm Hg caused significant reductions in CVP, systolic BP, and
      diastolic BP. These effects of nonhypotensive and hypotensive LBNP on CVP and BP
      were similar during ANP and NTG infusions, yet MSNA was lower both before and
      with LBNP during ANP (P<0.02). Nonhypotensive LBNP increased MSNA during NTG
      (+133+/-68 Units; P<0.001) but not during ANP infusion (+24+/-23 Units; P=NS).
      CONCLUSIONS: These observations are consistent with the concept that ANP exerts a
      sympathoinhibitory action in heart failure. This is most evident in response to
      reductions in atrial pressures that do not affect systemic BP.

PMID- 10199877
TI  - Gender differences in survival in advanced heart failure. Insights from the FIRST
      study.
AB  - BACKGROUND: Previous natural history studies in broad populations of heart
      failure patients have associated female gender with improved survival,
      particularly in patients with a nonischemic etiology of ventricular dysfunction.
      This study investigates whether a similar survival advantage for women would be
      evident among patients with advanced heart failure. METHODS AND RESULTS: The
      study analysis is based on the Flolan International Randomized Survival Trial
      (FIRST) study which enrolled 471 patients (359 men and 112 women) who had
      evidence of end-stage heart failure with marked symptoms (60% NYHA class IV) and
      severe left ventricular dysfunction (left ventricular ejection fraction 18+/
      4.9%). A Cox proportional-hazards model, adjusted for age, gender, 6-minute walk,
      dobutamine use at randomization, mean pulmonary artery blood pressure, and
      treatment assignment, showed a significant association between female gender and
      better survival (relative risk of death for men versus women was 2.18, 95% CI
      1.39 to 3.41; P<0.001). Although formal interaction testing was negative
      (P=0.275), among patients with a nonischemic etiology of heart failure, the
      relative risk of death for men versus women was 3.08 (95% CI 1.56 to 6.09,
      P=0.001), whereas among those with ischemic heart disease, the relative risk of
      death for men versus women was 1.64 (95% CI 0.87 to 3.09, P=0.127). CONCLUSIONS:
      Women with advanced heart failure appear to have better survival than men.
      Subgroup analysis suggests this finding is strongest among patients with a
      nonischemic etiology of heart failure.

PMID- 10199878
TI  - Impaired force-frequency relations in patients with hypertensive left ventricular
      hypertrophy. A possible physiological marker of the transition from physiological
      to pathological hypertrophy.
AB  - BACKGROUND: The extent to which force-frequency and relaxation-frequency
      relations (FFR and RFR, respectively) and exercise-induced adrenergic stimulation
      affect myocardial inotropic and lusitropic reserves has not been established in
      patients with left ventricular (LV) hypertrophy (LVH). METHODS AND RESULTS: We
      calculated the maximum first derivative of LV pressure (LV dP/dtmax) and the LV
      pressure half-time (T1/2) during pacing, exercise, and isoproterenol infusion in
      17 patients with hypertensive LVH and 9 control subjects to investigate the
      influence of increases in heart rate (HR) and adrenergic stimulation on inotropic
      and lusitropic reserves. Group A consisted of 10 LVH patients who showed a
      progressive increase in the HR-LV dP/dtmax relation. Group B consisted of 7 LVH
      patients in whom the HR-dP/dtmax relation at physiological pacing rates was
      biphasic. The LV mass index was larger and the LV ejection fraction was smaller
      in group B than in group A (244+/-72 g/m2 versus 172+/-22 g/m2 and 55+/-18%
      versus 72+/-6%, respectively; both P<0.05). The increase in LV dP/dtmax was
      greater during exercise than pacing alone for similar increases in HR in all
      groups (P<0.05) (group A, 111+/-22% versus 25+/-14%; group B, 105+/-35% versus
      14+/-10%; control, 111+/-24% versus 25+/-12%). T1/2 was shorter (P<0.05) during
      exercise than with pacing alone in all groups (group A, 41+/-6% versus 11+/-3%;
      group B, 38+/-9% versus 14+/-4%; control, 44+/-6% versus 12+/-5%). Isoproterenol
      infusion caused similar increases in LV dP/dtmax and similar decreases in T1/2 in
      all groups. CONCLUSIONS: The FFR was biphasic in patients with severe LVH
      irrespective of LV function but was preserved in patients with less severe LVH
      and control subjects. Importantly, the RFR and adrenergic control of both
      inotropic and lusitropic reserves were well preserved in all LVH patients. A
      biphasic FFR at physiological pacing rates may be one of the earliest markers of
      the transition from physiological adaptation to the pathological process in LVH
      patients.

PMID- 10199879
TI  - Blood pressure response during treadmill testing as a risk factor for new-onset
      hypertension. The Framingham heart study.
AB  - BACKGROUND: Although systolic blood pressure (SBP) response to exercise has been
      shown to predict subsequent hypertension in small samples of men, this
      association has not been studied in a large population-based sample of middle
      aged men and women. The purpose of this study was to examine, in normotensive
      subjects, the relations of SBP and diastolic blood pressure (DBP) during the
      exercise and recovery periods of a graded treadmill test to the risk of
      developing new-onset hypertension. METHODS AND RESULTS: BP data from exercise
      testing in 1026 men and 1284 women (mean age, 42+/-10 years; range, 20 to 69
      years) from the Framingham Offspring Study who were normotensive at baseline were
      related to the incidence of hypertension 8 years later. New-onset hypertension,
      defined as an SBP >/=140 mm Hg or DBP >/=90 mm Hg or the initiation of
      antihypertensive drug treatment, occurred in 228 men (22%) and 207 women (16%).
      Exaggerated SBP (Ex-SBP 2) and DBP (Ex-DBP 2) response and delayed recovery of
      SBP (R-SBP 3) and DBP (R-DBP 3) were defined as an age-adjusted BP greater than
      the 95th percentile during the second stage of exercise and third minute of
      recovery, respectively. After multivariable adjustment, Ex-DBP 2 was highly
      predictive of incident hypertension in both men (OR, 4.16; 95% CI, 2.15, 8.05)
      and women (OR, 2.17; CI, 1.19, 3.96). R-SBP 3 was predictive of hypertension in
      men in a multivariable model that included exercise duration and peak exercise BP
      (OR, 1.92; CI, 1.00, 3.69). Baseline resting SBP (chi2, 23.4 in men and 34.7 in
      women) and DBP (chi2, 11.3 in men and 13.1 in women) had stronger associations
      with new-onset hypertension than exercise DBP (chi2, 16.4 in men and 6.1 in
      women) and recovery SBP (chi2, 6.5 in men and 2.1 in women) responses.
      CONCLUSIONS: An exaggerated DBP response to exercise was predictive of risk for
      new-onset hypertension in normotensive men and women. An elevated recovery SBP
      was predictive of hypertension in men. These findings may reflect subtle
      pathophysiological features in the preclinical stage of hypertension.

PMID- 10199880
TI  - Effect of butorphanol tartrate on shock-related discomfort during internal atrial
      defibrillation.
AB  - BACKGROUND: In patients with atrial fibrillation, intracardiac atrial
      defibrillation causes discomfort. An easily applicable, short-acting analgesic
      and anxiolytic drug would increase acceptability of this new treatment mode.
      METHODS AND RESULTS: In a double-blind, placebo-controlled manner, the effect of
      intranasal butorphanol, an opioid, was evaluated in 47 patients with the use of a
      step-up internal atrial defibrillation protocol (stage I). On request, additional
      butorphanol was administered and the step-up protocol continued (stage II).
      Thereafter, if necessary, patients were intravenously sedated (stage III). After
      each shock, the McGill Pain Questionnaire was used to obtain a sensory (S),
      affective (A), evaluative (E), and total (T) pain rating index (PRI) and a visual
      analogue scale analyzing pain (VAS-P) and fear (VAS-F). For every patient, the
      slope of each pain or fear parameter against the shock number was calculated and
      individual slopes were averaged for the placebo and butorphanol group. All
      patients were cardioverted at a mean threshold of 4.4+/-3.3 J. Comparing both
      patient groups for stage II, the mean slopes for PRI-T (P=0.0099), PRI-S
      (P=0.019), and PRI-E (P=0.015) became significantly lower in the butorphanol
      group than in the placebo group. Comparing patients who received the same shock
      intensity ending stage I and going to stage II, in those patients randomized to
      placebo the mean VAS-P (P=0.023), PRI-T (P=0. 029), PRI-S (P=0.030), and PRI-E
      (P=0.023) became significantly lower after butorphanol administration.
      CONCLUSIONS: During a step-up internal atrial defibrillation protocol, intranasal
      butorphanol decreased or stabilized the value of several pain variables and did
      not affect fear. Of the 3 qualitative components of pain, only the affective
      component was not influenced by butorphanol. The PRI evaluated pain more
      accurately than the VAS.

PMID- 10199881
TI  - Prediction of sustained ventricular tachycardia inducible by programmed
      stimulation in patients with coronary artery disease. Utility of clinical
      variables.
AB  - BACKGROUND: Cardiologists often use clinical variables to determine the need for
      electrophysiological studies to stratify patients for risk of sudden death. It is
      not clear whether this is rational in patients with coronary artery disease, left
      ventricular dysfunction, and nonsustained ventricular tachycardia. METHODS AND
      RESULTS: We analyzed the first 1721 patients enrolled in the Multicenter
      UnSustained Tachycardia Trial to determine whether clinical variables could
      predict which patients would have inducible sustained monomorphic ventricular
      tachycardia. The rate of inducibility of sustained ventricular tachycardia was
      significantly higher in patients with a history of myocardial infarction and in
      men compared with women. There was a progressively increased rate of inducibility
      with increasing numbers of diseased coronary arteries. There was a significantly
      lower rate of inducibility in patients with prior coronary artery bypass surgery
      and in patients who also had noncoronary cardiac disease. The rate of
      inducibility was higher in patients of white race, patients with recent (</=6
      weeks) angina, left ventricular dyskinesis, and in patients with greater numbers
      of fixed thallium defects. Inducibility was more likely in patients who had a
      prior myocardial infarction complicated by congestive heart failure, ventricular
      tachycardia, or fibrillation </=48 hours after the onset of infarction. Although
      these associations are statistically significant, the accuracy of the clinical
      variables in discriminating between patients with and those without inducible
      ventricular tachycardia is only modest (receiver operator characteristic area
      <0.70). CONCLUSIONS: Multiple clinical variables are independently associated
      with inducible sustained ventricular tachycardia. However, they have limited
      utility to guide clinical decisions regarding the use of electrophysiological
      testing for risk stratification in this patient population.

PMID- 10199882
TI  - Mortality and morbidity of aortic regurgitation in clinical practice. A long-term
      follow-up study.
AB  - BACKGROUND: The outcome of aortic regurgitation conservatively followed in
      clinical practice is poorly defined. METHODS AND RESULTS: Long-term outcome of
      246 patients with severe or moderately severe aortic regurgitation diagnosed by
      color Doppler echocardiography was analyzed. With conservative management,
      mortality rate was higher than expected (at 10 years, 34+/-5%, P<0. 001) and
      morbidity was high (10-year rates of 47+/-6% for heart failure and 62+/-4% for
      aortic valve surgery). At 10 years, 75+/-3% of patients had died or had surgery
      and 83+/-3% had had cardiovascular events. In multivariate analysis, predictors
      of survival were age (P<0.001), functional class (P<0.001), comorbidity index
      (P=0.033), atrial fibrillation (P=0.002), and left ventricular end-systolic
      diameter corrected for body surface area (P=0.025). Ejection fraction was also an
      independent predictor of overall survival, including postoperative follow-up of
      surgically treated patients (P<0.001). High risk during conservative treatment,
      with mortality rate in excess of that expected, was noted among patients with
      severe, even transient, symptoms (24.6% yearly, P<0.001) but also in those with
      mild (class II) symptoms (6.3% yearly, P=0.02) and in asymptomatic patients with
      left ventricular ejection fraction <55% (5.8% yearly, P=0.03) or with end
      systolic diameter normalized to body surface area >/=25 mm/m2 (7.8% yearly,
      P=0.004). Surgery performed during follow-up was independently associated with
      reduced cardiovascular mortality (adjusted hazard ratio, 0.54; P=0.048).
      CONCLUSIONS: Patients diagnosed with severe aortic regurgitation in clinical
      practice incur excess mortality and high morbidity, underscoring the serious
      prognosis of the disease. Surgery, which reduces cardiac mortality rates, should
      be considered promptly in high-risk patients.

PMID- 10199883
TI  - Long-term prostacyclin for pulmonary hypertension with associated congenital
      heart defects.
AB  - BACKGROUND: Although long-term prostacyclin (PGI2) has been shown to improve
      hemodynamics, quality of life, and survival in patients with primary pulmonary
      hypertension, its use in patients with pulmonary hypertension (PHT) and
      associated congenital heart defects (CHD) has not been evaluated. METHODS AND
      RESULTS: Twenty patients (15+/-14 years) with PHT and associated CHD (9 atrial
      septal defect, 7 ventricular septal defect, 4 transposition of the great vessels,
      3 patient ductus arteriosus, 3 partial anomalous pulmonary venous return, and 1
      aortopulmonary window) who failed conventional therapy (including digitalis;
      diuretics; oxygen; warfarin; calcium channel blockade, if indicated; and surgery,
      if operable) were treated with chronic PGI2. Eleven patients had previous cardiac
      surgery at a median age of 3 years (range, 5 days to 47 years). Eleven of 20
      patients had residual systemic to pulmonary shunts. Hemodynamics, NYHA functional
      class, and exercise capacity were measured at baseline and after 1 year of PGI2
      therapy. None of the patients acutely responded to PGI2 administration. Despite
      lack of an acute response, mean pulmonary artery pressure decreased 21% on
      chronic PGI2: 77+/-20 to 61+/-15 mm Hg (P<0.01, n=16). Cardiac index and
      pulmonary vascular resistance also improved on long-term PGI2: 3. 5+/-2.0 to
      5.9+/-2.7 L. min-1. m-2 (P<0.01, n=16), and 25+/-13 to 12+/-7 U.m2 (P<0.01,
      n=16), respectively. NYHA functional class improved from 3.2+/-0.7 to 2.0+/-0.9
      (P<0.0001, n=19). Exercise capacity increased from 408+/-149 to 460+/-99 m
      (P=0.13, n=14) on long-term PGI2. CONCLUSIONS: Chronic PGI2 improves hemodynamics
      and quality of life in patients with PHT and associated CHD who fail conventional
      therapy. As previously demonstrated in patients with primary pulmonary
      hypertension, long-term PGI2 may have an important role in the treatment of
      patients with PHT and associated CHD.

PMID- 10199884
TI  - Serial assessment of sympathetic reinnervation after orthotopic heart
      transplantation. A longitudinal study using PET and C-11 hydroxyephedrine.
AB  - BACKGROUND: Little is known about the progressiveness of sympathetic
      reinnervation late after cardiac transplantation (HTX). The aim of the present
      study was to describe individual growth of sympathetic terminals after HTX by a
      longitudinal quantitative assessment. METHODS AND RESULTS: In 20 patients after
      HTX, dynamic PET with C-11 hydroxyephedrine (HED) was performed twice within
      3.0+/-0.5 years. According to the time interval between HTX and first PET,
      subgroups of patients early (group A, <1.5 years; n=7), intermediate (group B,
      1.5 to 7 years; n=7) and late (group C, >7 years; n=6) after HTX were defined. At
      the time of first HED PET, 10 patients were completely denervated (7 in group A,
      2 in group B, and 1 in group C). Only 3 remained denervated at second PET. A
      significant increase of reinnervated myocardium between first and second PET was
      found in all 3 groups (0% to 9+/-9% of left ventricle for group A, P<0.05; 13+/
      12% to 23+/-17% for group B, P<0.05; 21+/-21% to 37+/-23% for group C, P<0.05).
      The magnitude of increase was similar between groups. Reinnervation was first
      surveyed in the basal anterior region, then toward apex, septal, and lateral
      wall. Inferior wall remained denervated. The largest reinnervated area surveyed
      in an individuum was 66% of the left ventricle. CONCLUSIONS: The present data
      confirm the low likelihood of sympathetic reinnervation within 18 months after
      HTX. Once the reinnervation process is initiated, a continuous growth is observed
      even late after HTX, suggesting a progressive nature of reinnervation.
      Reinnervation, however, remained regionally heterogeneous, and a complete
      restoration was not found until 15 years after HTX.

PMID- 10199885
TI  - ApoCIII gene variants modulate postprandial response to both glucose and fat
      tolerance tests.
AB  - BACKGROUND: We investigated the relationship between variation in the
      apolipoprotein (apo) AI-CIII-AIV gene cluster and response to an oral glucose
      test (OGTT) and oral fat load test (OFTT) in the EARSII group of young, healthy
      male offspring whose fathers had had a myocardial infarction before the age of 55
      years (cases, n=407) compared with age-matched controls (n=415). The apoCIII
      variations examined were C3238G (SstI) in the 3'-UTR, C1100T in exon 3, C-482T in
      the insulin response element (IRE), and T-2854G in the apoCIII-AIV intergenic
      region. METHODS AND RESULTS: The postprandial response was regulated by variation
      at the T-2854G and C3238G sites. After the OFTT, carriers of the rare alleles had
      delayed clearance of triglyceride (Tg) levels; G-2854 carriers showed the largest
      effect on Tg (AUC, 24% greater, P<0.002; peak, 19% greater, P<0.005), and G3238
      carriers showed a smaller response (AUC, 13% greater, P<0.05; peak, 13% greater,
      P=0.03). However, after adjustment for fasting level of Tg, only the effect with
      the T-2854G remained significant. Variation at the C-482T (IRE) determined
      response to the OGTT, with carriers of the rare T-482 having significantly
      elevated glucose (28.7% AUC, P=0.013) and insulin (20.5% AUC, P<0. 01)
      concentrations. CONCLUSIONS: These data suggest that specific genetic variants at
      the apoCIII gene locus differentially affect postprandial and response to OGTT
      and suggest a novel mechanism for the effects of variation at this locus on risk
      for atherosclerosis.

PMID- 10199886
TI  - Proinflammatory mediators chronically downregulate the formation of the
      endothelium-derived hyperpolarizing factor in arteries via a nitric oxide/cyclic
      GMP-dependent mechanism.
AB  - BACKGROUND: Endothelium-dependent dilator responses mediated by NO and
      endothelium-derived hyperpolarizing factor (EDHF) are altered in arteriosclerosis
      and sepsis. The possibility that proinflammatory mediators that stimulate the
      expression of inducible NO synthase (NOS II) affect the generation of EDHF was
      examined in isolated arteries. METHODS AND RESULTS: Under combined blockade of
      NOS and cyclooxygenase, EDHF-mediated relaxation elicited by several agonists was
      significantly attenuated in rabbit carotid and porcine coronary arteries exposed
      to cytokines and lipopolysaccharide. The blunted relaxation was coincident with
      NOS II expression and was prevented by inhibition of NOS II as well as of global
      protein synthesis. The NO donor CAS 1609 and 8-bromo-cGMP mimicked the
      proinflammatory mediator effect. In contrast, long-term blockade of endothelial
      NO generation increased the relaxation in carotid but not in coronary arteries.
      Proinflammatory mediators reduced the synthesis of EDHF assessed as
      hyperpolarization of vascular smooth muscle cells elicited by the effluent from
      bradykinin-stimulated coronary arteries. Proinflammatory mediators induced NOS II
      expression in cultured endothelial cells and decreased the expression of
      cytochrome P450 enzymes, which are the most probable candidates for the synthesis
      of EDHF. CONCLUSIONS: Proinflammatory mediators inhibit the formation of EDHF in
      isolated arteries. This impairment is coincident with NOS II expression in the
      arterial wall and seems to be mediated through the induced generation of NO,
      which downregulates the putative EDHF-forming enzyme. Thus, a decreased formation
      of EDHF may contribute to the endothelial dysfunction in arteriosclerosis and
      sepsis.

PMID- 10199887
TI  - Generation of humanized mice susceptible to peptide-induced inflammatory heart
      disease.
AB  - BACKGROUND: Dilated cardiomyopathy (DCM) is a major cause of sudden cardiac
      death. In certain mouse major histocompatibility complex (MHC) backgrounds,
      myocarditis and inflammatory cardiomyopathy can be triggered by immunization with
      heart muscle-specific proteins. Similarly, chronic heart disease in humans has
      been linked to certain HLA alleles, such as HLA-DQ6. However, there is no
      experimental evidence showing that human MHC class II molecules and peptides
      derived from human proteins are involved in the pathogenesis of myocarditis and
      DCM. METHODS AND RESULTS: We generated double CD4- and CD8-deficient mice
      transgenic for human CD4 (hCD4) and human HLA-DQ6 to specifically reconstitute
      the human CD4/DQ6 arm of the immune system in mice. Transgenic hCD4 and HLA-DQ6
      expression rendered genetically resistant C57BL/6 mice susceptible to the
      induction of autoimmune myocarditis induced by immunization with cardiac myosin.
      Moreover, we identified heart-specific peptides derived from both mouse and human
      alpha-myosin heavy chains capable of inducing inflammatory heart disease in hCD4
      and HLA-DQ6 double transgenic mice but not in hCD4 single transgenic littermates.
      The autoimmune inflammatory heart disease induced by the human heart muscle
      specific peptide in hCD4 and HLA-DQ6 double transgenic mice shared functional and
      phenotypic features with the disease occurring in disease-susceptible
      nontransgenic mice. CONCLUSIONS: Our data provide the first genetic and
      functional evidence that human MHC class II molecules and a human alpha-myosin
      heavy chain-derived peptide can cause inflammatory heart disease and suggest that
      human inflammatory cardiomyopathy can be caused by organ-specific autoimmunity.
      The humanized mice generated in this study will be an ideal animal model to
      further elucidate the pathogenesis of inflammatory heart disease and facilitate
      the development of rational treatment strategies.

PMID- 10199888
TI  - Myocardial lactate metabolism in fetal and newborn lambs.
AB  - BACKGROUND: Around birth, myocardial substrate supply changes from carbohydrates
      before birth to primarily fatty acids after birth. Parallel to these changes, the
      myocardium is expected to switch from the use of primarily lactate before birth
      to fatty acids thereafter. However, myocardial lactate uptake and oxidation
      around birth has not been measured in vivo. METHODS AND RESULTS: We measured
      myocardial lactate uptake, oxidation, and release with infusion of [1-13C]lactate
      and myocardial flux of fatty acids and glucose in chronically instrumented fetal
      and newborn (1 to 15 days) lambs. Myocardial lactate oxidation was the same in
      newborn (81.7+/-14.7 micromol. min-1. 100 g-1, n=11) as in fetal lambs (60.7+/
      26.7 micromol. min-1. 100 g-1, n=7). Lactate uptake was also the same in newborn
      as in fetal lambs. Lactate uptake was higher than lactate flux, indicating
      lactate release simultaneously with uptake. In the newborn lambs, lactate uptake
      declined with age. Lactate uptake was strongly related to lactate supply, whereas
      lactate oxidation was not. The supply of fatty acids or glucose did not interfere
      with lactate uptake, but the flux of fatty acids was inversely related to lactate
      oxidation. CONCLUSIONS: We show that lactate is an important energy source for
      the myocardium before birth as well as in the first 2 weeks after birth in lambs.
      We also show that there is release of lactate by the myocardium simultaneously
      with uptake of lactate. Furthermore, we show that lactate oxidation may be
      attenuated by fatty acids but not by glucose, probably at the level of pyruvate
      dehydrogenase.

PMID- 10199889
TI  - Transient outward current, Ito1, is altered in cardiac memory.
AB  - BACKGROUND: Cardiac memory refers to an altered T-wave morphology induced by
      ventricular pacing or arrhythmias that persist for variable intervals after
      resumption of sinus rhythm. METHODS AND RESULTS: We induced long-term cardiac
      memory (LTM) in conscious dogs by pacing the ventricles at 120 bpm for 3 weeks.
      ECGs were recorded daily for 1 hour, during which time pacing was discontinued.
      At terminal study, the heart was removed and the electrophysiology of left
      ventricular epicardial myocytes was investigated. Control (C) and LTM ECG did not
      differ, except for T-wave amplitude, which decreased from 0.12+/-0.18 to -0.34+/
      0.21 mV (+/-SEM, P<0.05), and T-wave vector, which shifted from -37+/-12 degrees
      to -143+/-4 degrees (P<0.05). Epicardial action potentials revealed loss of the
      notch and lengthening of duration at 20 days (both P<0.05). Calcium-insensitive
      transient outward current (Ito) was investigated by whole-cell patch clamp. No
      difference in capacitance was seen in C and LTM myocytes. Ito activated on
      membrane depolarization to -25+/-1 mV in C and -7+/-1 mV (P<0.05) in LTM
      myocytes, indicating a positive voltage shift of activation. Ito density was
      reduced in LTM myocytes, and a decreased mRNA level for Kv4.3 was observed.
      Recovery of Ito from inactivation was significantly prolonged: it was 531+/-80 ms
      (n=10) in LTM and 27+/-6 ms (n=9) in C (P<0.05) at -65 mV. CONCLUSIONS: Ito
      changes are associated with and can provide at least a partial explanation for
      action-potential and T-wave changes occurring with LTM.

PMID- 10199890
TI  - Mapping of atrial activation with a noncontact, multielectrode catheter in dogs.
AB  - BACKGROUND: Endocardial mapping of sustained arrhythmias has traditionally been
      performed with a roving diagnostic catheter. Although this approach is adequate
      for many tachyarrhythmias, it has limitations. The purpose of this study was to
      evaluate a novel noncontact mapping system for assessing atrial tachyarrhythmias.
      METHODS AND RESULTS: The mapping system consists of a 9F multielectrode-array
      balloon catheter that has 64 active electrodes and ring electrodes for emitting a
      locator signal. The locator signal was used to construct a 3-dimensional right
      atrial map; it was independently validated and was highly accurate. Virtual
      electrograms were calculated at 3360 endocardial sites in the right atrium. We
      evaluated right atrial activation by positioning the balloon catheter in the mid
      right atrium via a femoral venous approach. Experiments were performed on 12
      normal mongrel dogs. The mean correlation coefficient between contact and virtual
      electrograms was 0.80+/-0.12 during sinus rhythm. Fifty episodes of atrial
      flutter induced in 11 animals were evaluated. In the majority of experiments,
      complete or almost complete reentrant circuits could be identified within the
      right atrium. Mean correlation coefficient between virtual and contact
      electrograms was 0.85+/-0.17 in atrial flutter. One hundred fifty-six episodes of
      pacing-induced atrial fibrillation were evaluated in 11 animals. Several distinct
      patterns of right atrial activation were seen, including single-activation wave
      fronts and multiple simultaneous-activation wave fronts. Mean correlation
      coefficient between virtual and contact electrograms during atrial fibrillation
      was 0.81+/-0.18. The accuracy of electrogram reconstruction was lower at sites
      >4.0 cm from the balloon center and at sites with a high spatial complexity of
      electrical activation. CONCLUSIONS: This novel noncontact mapping system can
      evaluate conduction patterns during sinus rhythm, demonstrate reentry during
      atrial flutter, and describe right atrial activation during atrial fibrillation.
      The accuracy of electrogram reconstruction was good at sites <4.0 cm from the
      balloon center, and thus the system has the ability to perform high-resolution
      multisite mapping of atrial tachyarrhythmias in vivo.

PMID- 10199891
TI  - Electrocardiographic abnormalities in a murine model injected with IgG from
      mothers of children with congenital heart block.
AB  - BACKGROUND: It is a widely held view that congenital heart block (CHB) is caused
      by the transplacental transfer of maternal autoantibodies (anti-SSA/Ro and/or
      anti-SSB/La) into the fetal circulation. To test this hypothesis and to reproduce
      human CHB, an experimental mouse model (BALB/c) was developed by passive transfer
      of human autoantibodies into pregnant mice. METHODS AND RESULTS: Timed pregnant
      mice (n=54) were injected with a single intravenous bolus of purified IgG
      containing human anti-SSA/Ro and anti-SSB/La antibodies from mothers of children
      with CHB. To parallel the "window period" of susceptibility to CHB in humans, 3
      groups of mice were used: 8, 11, and 16 days of gestation. Within each group, we
      tested 10, 25, 50, and 100 microg of IgG. At delivery, ECGs were recorded and
      analyzed for conduction abnormalities. Bradycardia and PR interval were
      significantly increased in 8-, 11-, and 16-day gestational groups when compared
      with controls (P<0.05). QRS duration was not significantly different between all
      groups. Antibody levels measured by ELISA in both mothers and their offspring
      confirmed the transplacental transfer of the human antibodies to the pups.
      CONCLUSIONS: The passive transfer model demonstrated bradycardia, first-degree
      but not complete atrioventricular block in pups. The greater percentage and
      degree of bradycardia and PR prolongation in the 11-day mouse group correlates
      with the "window period" of susceptibility observed in humans. The high incidence
      of bradycardia suggests possible sinoatrial node involvement. All together, these
      data provide relevant insights into the pathogenesis of CHB.

PMID- 10199892
TI  - Non-Q-wave infarction and ostial left coronary obstruction due to giant Lambl's
      excrescences of the aortic valve.

PMID- 10199893
TI  - Hypercholesterolemia, abnormal coronary vasomotion, and calcium antagonists.

PMID- 10199894
TI  - ILCOR advisory statement: resuscitation of the newly born infant. An advisory
      statement from the pediatric working group of the International Liaison Committee
      on Resuscitation.

PMID- 10199895
TI  - Correction 

PMID- 10199896
TI  - Radiofrequency ablation of atrial flutter.

PMID- 10199897
TI  - Malignancies in pediatric patients with ataxia telangiectasia.
AB  - BACKGROUND: Patients with ataxia telangiectasia (AT), known to have an inherent
      increased susceptibility to the development of cancer, may present with
      malignancies that are unusual for the patient's age, are often difficult to
      diagnose clinically and radiographically and respond poorly to conventional
      therapy. MATERIALS AND METHODS: We reviewed the clinical presentation and imaging
      studies of 12 AT patients who developed malignancies. RESULTS: Eight of the
      twelve patients developed non-Hodgkin's lymphoma (CNS, thorax, bone), two
      developed Hodgkin's disease, and two were diagnosed with gastrointestinal
      mucinous adenocarcinoma. CONCLUSION: The lymphomas were commonly extra nodal, and
      infiltrative rather than mass-like. The recognition of the tumors was often
      delayed due to confusion with the known infectious complications in AT patients.

PMID- 10199898
TI  - Hepatic adenomatosis: rapid sequence MR imaging following gadolinium enhancement:
      a case report.
AB  - Hepatic adenomas are primary liver tumors usually associated with underlying
      metabolic disease or with anabolic steroid or oral contraceptive use. Hepatic
      adenomatosis (HA) is defined as the presence of more than four adenomas. Only 13
      cases of HA have been reported in patients without glycogen storage disease or
      steroid use. We report a case of HA imaged by postcontrast T1-weighted images
      obtained during a breath-holding series. The lesions were most conspicuous 3-4
      min after contrast administration; 4 of the 5 tumors were not identified on T2
      weighted images. Unlike previous reports of HA in which the lesions remained
      hyperintense during sequential postcontrast imaging, the smaller lesions in this
      case demonstrated contrast washout, thereby distinguishing them from
      hemangiomata.

PMID- 10199899
TI  - Congenital absence of the portal vein in a boy.
AB  - Congenital absence of the portal vein (CAPV) is a malformation that is generally
      thought to be limited to females. We encountered an 11-year-old boy with this
      malformation. In 17 previously reported cases of CAPV, 2 were male. Three male
      patients, including our case, were Abernethy type Ib malformation. They had no
      associated liver tumour and two had no additional congenital abnormality.
      Conversely, 13 of the 15 female patients had congenital abnormalities and 6 had
      liver mass lesions.

PMID- 10199900
TI  - Applications of magnetic resonance imaging and magnetic resonance angiography to
      evaluate the hepatic vasculature in the pediatric patient.
AB  - Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) offer
      several techniques to evaluate the hepatic vasculature. These techniques are
      briefly reviewed with reference to the pediatric population. Examples of MRI and
      MRA in the evaluation of the hepatic vasculature in pediatric patients are
      presented.

PMID- 10199901
TI  - Adult diseases in children.
AB  - The classic teaching in performance and interpretation of diagnostic studies is
      that "children are not small adults." The purpose of this article is to show a
      spectrum of "adult" disease entities that can occur, but are not usually
      considered in the pediatric population: cricopharyngeal achalasia, Schatzki's
      ring, achalasia, Helicobacter pylori, pancreatic carcinoma, adenocarcinoma of the
      colon, nasopharyngeal carcinoma, thyroid carcinoma, malignant melanoma,
      hydatidiform mole, renal cell carcinoma, leiomyosarcoma of the ovary and
      sarcoidosis. Radiologists interpreting pediatric imaging should recognize these
      entities and perform an appropriate diagnostic workup.

PMID- 10199902
TI  - Evaluation of a method of assessing faecal loading on plain abdominal radiographs
      in children.
AB  - BACKGROUND: Childhood constipation is common and assessment is often difficult.
      Plain abdominal radiography is simple and commonly used to assess constipation.
      The role of radiography with the use of a simple scoring system has not been
      fully evaluated. OBJECTIVE: To assess the reliability of scoring faecal loading
      on plain abdominal radiographs in children with intractable constipation.
      MATERIALS AND METHODS: Plain abdominal radiographs from 33 constipated and 67
      control children were independently assessed by three observers on two separate
      occasions. A scoring system was devised with scores from 0 (no stool) to 5 (gross
      faecal loading with bowel dilatation) in three areas of the colon, giving a total
      score of 0-15. RESULTS: There were significant differences between the scores of
      the constipated and control radiographs for each observer (P = 0.05). There was
      no intra-observer variation (P = 0.12-0.69), but significant inter-observer
      variation was demonstrated (P = 0.00). CONCLUSIONS: We have found this scoring
      system to be a clinically useful and a reproducible tool in assessing childhood
      constipation. Assessment of faecal loading is subjective and varies between
      observers, although one observer will consistently score faecal loading on the
      same radiograph on successive occasions. To limit exposure to ionising radiation,
      we recommend that radiography be reserved for the investigation of intractable
      constipation, and its accuracy is improved if all radiographs are scored by the
      same observer.

PMID- 10199903
TI  - MR imaging in longitudinal epiphyseal bracket in children.

PMID- 10199904
TI  - MRI multiplanar reconstruction in the assessment of congenital talipes
      equinovarus.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) has been shown to be a useful tool
      in the evaluation of the complex deformities which are present in congenital
      talipes equinovarus (clubfoot). OBJECTIVE: To evaluate MRI with the multiplanar
      reconstruction (MPR) technique as a new method for assessment of clubfoot.
      MATERIALS AND METHODS: Seven infants with 11 clubfeet were studied by using three
      dimensional gradient-echo MR sequences. MPR was performed from the acquired image
      data in orthogonal, single and double oblique planes to demonstrate the complex
      deformities in clubfoot. Three angles (talar body-neck angle, talocalcaneal left
      right angle and the talocalcaneal superior-inferior angle) were defined for
      measuring the medial angulation of the talar neck and the rotation of the
      calcaneus in relation to the talus. RESULTS: The method clearly demonstrated the
      pathological anatomy of the clubfeet, especially the talonavicular articulations.
      Dislocation of the navicular bone was observed in 9 of the 11 feet. The angle
      measurements were easily conducted with MPR, and these angles differed
      considerably among the patients. CONCLUSIONS: The information provided by this
      method is useful for classification of the severity of clubfoot deformities.

PMID- 10199905
TI  - A case of oral-facial-digital syndrome with overlapping manifestations of type V
      and type VI: a possible new OFD syndrome.
AB  - We report a child with clinical and radiological manifestations characteristic of
      both V'aradi syndrome (oral-facial-digital syndrome type VI) and Thurston
      syndrome (oral-facial-digital syndrome type V). The findings have not been
      reported previously, and we believe that it represents a new variant.

PMID- 10199906
TI  - Ewing's sarcoma recurrence vs radiation necrosis in dynamic contrast-enhanced MR
      imaging: a case report.
AB  - PURPOSE: We report a case of Ewing's sarcoma in the right distal femur in a 6
      year-old male to demonstrate how dynamic contrast-enhanced magnetic resonance
      imaging (DEMRI) findings predicted histopathology. MATERIALS AND METHODS: DEMRI
      was performed at presentation and during and after completion of chemotherapy and
      radiation therapy. Histopathologic studies were done at presentation, at 77 weeks
      (20 weeks after a pathological fracture), and from the en bloc resection at 104
      weeks. RESULTS: DEMRI predicted the early tumor response, absence of tumor
      recurrence, presence of necrosis and lack of fracture healing, confirmed by
      histopathology. CONCLUSION: DEMRI is a clinically useful tool in managing Ewing's
      sarcoma.

PMID- 10199907
TI  - MRI diagnosis of suspected atlanto-occipital dissociation in childhood.
AB  - OBJECTIVE: To demonstrate the utility of magnetic resonance (MR) imaging in the
      diagnosis of complete and partial ligamentous injuries in patients with suspected
      atlanto-occipital dissociation (AOD). MATERIALS AND METHODS: Five patients with
      suspected AOD had MR imaging performed within an average of 4 days after injury.
      MR scans were reviewed with specific analysis of craniocervical ligamentous
      structures. Charts were reviewed to obtain clinical information regarding
      presentation, treatment, hospital course, and outcome. RESULTS: Two patients
      demonstrated MR evidence of complete AOD. One had disruption of all visualized
      major ligamentous structures at the craniocervical junction with anterolisthesis
      and evidence of cord damage. The second had injuries to the tectorial membrane,
      superior band of the cruciform ligament, apical ligament, and interspinous
      ligament at C 1-2. The remaining three patients sustained incomplete severance of
      the ligamentous structures at the craniocervical junction. All patients
      demonstrated subtle radiographic findings suggestive of AOD, including soft
      tissue swelling at the craniocervical junction without fracture. The two patients
      with complete AOD died. The three patients with partial AOD were treated with
      stabilization. On follow-up, these three children were asymptomatic following
      their craniocervical injury. CONCLUSION: MR imaging of acute AOD provides
      accurate identification of the craniocervical ligaments injured, classification
      of full versus partial ligamentous disruption, and analysis of accompanying
      spinal cord injury. This information is important for early appropriate
      neurosurgical management and preservation of neurologic function in survivors.

PMID- 10199908
TI  - Sequential MRI, SPECT and PET in respiratory syncytial virus encephalitis.
AB  - We report on a 3-year-old girl with respiratory syncytial virus (RSV)
      encephalitis manifested by disturbance of consciousness, conjugate eye deviation,
      anuria, truncal ataxia and intention tremor. T2-weighted magnetic resonance
      imaging (MRI) showed hyperintense areas in the cerebellar cortex. No lesion was
      detected in the cerebral cortex, pons or spinal cord. The hyperintense areas in
      the cerebellar cortex diminished with recovery from the clinical manifestations
      and had resolved 2 months after onset. The MRI lesions in the cerebellum were
      considered to be due to oedema. SPECT and positron emission tomography (PET),
      performed 3 months after onset, disclosed areas of hypoperfusion and
      hypometabolism at the same sites. One year after onset, MRI showed mild atrophy
      of the cerebellum. Hypoperfusion on SPECT and hypometabolism on PET remained.
      Neuroimaging showed that ataxia and tremor in this case were the result of
      cerebellitis. The patient has no neurological deficit except for mild truncal
      ataxia. This patient is a rare example of RSV encephalitis.

PMID- 10199909
TI  - A survey of post-discharge side effects of conscious sedation using chloral
      hydrate in pediatric CT and MR imaging.
AB  - BACKGROUND: Limited information is available on post-discharge side effects of
      chloral hydrate sedation in pediatric imaging. OBJECTIVE: To prospectively study
      the post-discharge side effects of chloral hydrate sedation in pediatric CT and
      MR imaging. MATERIALS AND METHODS: A total of 119 children undergoing CT and MRI
      were sedated using chloral hydrate with 89 % success (mean initial dose, 72 mg/kg
      body weight) and 98 % success after augmentation (mean total, 78 mg/kg body
      weight). The frequency of each post-discharge side effect was correlated with
      other side effects and 12 patient/technical parameters. RESULTS: The survey was
      completed in 80 children. Sleepiness lasted for > 4 h in 28 %. Unsteadiness
      occurred in 68 % and hyperactivity in 29 %. Appetite became poor in 14 % and
      vomiting occurred in 15 %. Normal activity was resumed after > 4 h in 54 %. Sleep
      deprivation did not result in increased success or earlier onset of sedation and
      might be associated with hyperactivity. A higher dose did not result in an
      increased success rate or earlier onset of sedation within the dose range used in
      this study. CONCLUSION: Data on the post-discharge side effects of chloral
      hydrate sedation will be useful to radiologists, technologists, and nurses
      explaining to parents about sedation using this agent.

PMID- 10199910
TI  - Assessment of increase in renal pelvic size on post-void sonography as a
      predictor of vesicoureteral reflux.
AB  - BACKGROUND: During the course of our routine renal ultrasound examinations, we
      noticed that some children who developed dilatation of a renal pelvis following
      voiding had reflux found on voiding cystourethrography (VCUG). PURPOSE: To
      determine if increase in renal pelvic size on post-void ultrasound is an accurate
      predictor of vesicoureteral reflux. MATERIALS AND METHODS: Fifty-seven children
      (113 kidneys) underwent renal ultrasound and VCUG on the same day.
      Anteroposterior dimensions of the renal pelves were prospectively measured on
      ultrasound prior to and following patient voiding and correlated with the results
      of the VCUG. RESULTS: The diameter of the renal pelvis increased in 12 and
      decreased in 38 kidneys on post-void ultrasound. Vesicoureteral reflux occurred
      in 19 kidneys and among these kidneys, renal pelvic diameter increased in 2,
      decreased in 7, and was unchanged in 10 following voiding. There was no
      significant correlation between post-void change in renal pelvic diameter and the
      presence of vesicoureteral reflux. CONCLUSION: Increase in renal pelvic size on
      post-void ultrasound is not a reliable indicator of vesicoureteral reflux.

PMID- 10199911
TI  - Development of a life-threatening anaphylactoid reaction following administration
      of ioversol in a child.
AB  - We report for the first time the case of a 3-year-old girl who developed a severe
      anaphylactoid reaction following the administration of the nonionic, low osmolar
      intravenous radiographic contrast agent ioversol. Severe reactions to ioversol
      have rarely been reported in adult patients and to our knowledge never in
      children. Health care providers managing children who may require radiologic
      imaging studies with ioversol should be aware of the potential complications of
      this radiographic contrast agent.

PMID- 10199912
TI  - Molecular cloning of the human gene STK10 encoding lymphocyte-oriented kinase,
      and comparative chromosomal mapping of the human, mouse, and rat homologues.
AB  - LOK is a new and unique member of the STE20 family with serine/threonine kinase
      activity, and its expression is restricted mostly to lymphoid cells in mice. We
      cloned the cDNA encoding the human homologue of LOK. The amino acid sequence
      deduced from the cDNA shows a high similarity to that of mouse LOK, with 88%
      identity as a whole. The kinase domains at the N-terminus and the coiled-coil
      regions at the C-terminus are particularly conserved, showing 98% and 93%
      identity, respectively. Western blot analysis with mouse LOK-specific antibody
      detected 130 000 Mr LOK proteins in human and rat lymphoid cell lines and
      tissues. The gene encoding the LOK (STK10/Stk10) gene was mapped by fluorescence
      in situ hybridization to chromosome 5q35.1 in human, chromosome 11A4 in mouse,
      and chromosome 10q12.3 in rat. By virtue of polymorphic CA repeats found in the
      3' untranslated region of the mouse Stk10 gene, the Stk10 locus was further
      pinpointed to chromosome 11 between D11Mit53 and D11Mit84, using the
      intersubspecific backcross mapping panel. These results established STK10 as a
      new marker of human chromosome 5 to define the syntenic boundary of human
      chromosomes 5 and 16 on mouse chromosome 11.

PMID- 10199913
TI  - Molecular cloning and characterization of CD4 in an aquatic mammal, the white
      whale Delphinapterus leucas.
AB  - Given the importance of the cell surface recognition protein, CD4, in immune
      function, the cloning and characterization of CD4 at the molecular level from an
      odontocete cetacean, the white whale (Delphinapterus leucas), was carried out.
      Whale CD4 cDNA contains 2662 base pairs and translates into a protein containing
      455 amino acids. Whale CD4 shares 64% and 51% identity with the human and mouse
      CD4 protein, respectively, and is organized in a similar manner. Unlike human and
      mouse, however, the cytoplasmic domain, which is highly conserved, contains amino
      acid substitutions unique to whale. Moreover, only one of the seven potential N
      linked glycosylation sites present in whale is shared with human and mouse.
      Evolutionarily, the whale CD4 sequence is most similar to pig and structurally
      similar to dog and cat, in that all lack the cysteine pair in the V2 domain.
      These differences suggest that CD4 may have a different secondary structure in
      these species, which may affect binding of class II and subsequent T-cell
      activation, as well as binding of viral pathogens. Interestingly, as a group,
      species with these CD4 characteristics all have high constitutive expression of
      class II molecules on T lymphocytes, suggesting potential uniqueness in the
      interaction of CD4, class II molecules, and the immune response. Molecular
      characterization of CD4 in an aquatic mammal provides information on the CD4
      molecule itself and may provide insight into adaptive evolutionary changes of the
      immune system.

PMID- 10199914
TI  - Gene organization of the quail major histocompatibility complex (MhcCoja) class I
      gene region.
AB  - Class I genomic clones of the quail (Coturnix japonica) major histocompatibility
      complex (MhcCoja) were isolated and characterized. Two clusters spanning the 90.8
      kilobase (kb) and 78.2 kb class I gene regions were defined by overlapping cosmid
      clones and found to contain at least twelve class I loci. However, unlike in the
      chicken Mhc, no evidence for the existence of any Coja class II gene was obtained
      in these two clusters. Based on comparative analysis of the genomic sequences
      with those of the cDNA clones, Coja-A, Coja-B, Coja-C, and Coja-D (Shiina et al.
      1999), these twelve loci were assigned to represent one Coja-A gene, two Coja-B
      genes (Coja-B1 and -B2), four Coja-C genes (Coja-C1-C4), four Coja-D genes (Coja
      D1-D4), and one new Coja-E gene. A class I gene-rich segment of 24.6 kb in which
      five of these genes (Coja-B1, -B2, -D1, -D2 and -E) are densely packed were
      sequenced by the shotgun strategy. All of these five class I genes are very
      compact in size [2089 base pairs (bp)-2732 bp] and contain no apparent genetic
      defect for functional expression. A transporter associated with the antigen
      processing (TAP) gene was identified in this class I gene-rich segment. These
      results suggest that the quail class I region is physically separated from the
      class II region and characterized by a large number of the expressible class I
      loci (at least seven) in contrast to the chicken Mhc, where the class I and class
      II regions are not clearly differentiated and only at most three expressed class
      I loci so far have been recognized.

PMID- 10199916
TI  - The P5 multicopy gene family in the MHC is related in sequence to human
      endogenous retroviruses HERV-L and HERV-16.
AB  - P5 is believed to be a multicopy gene family with at least eight members
      restricted to the major histocompatibility complex (MHC). Although the function
      of P5 genes is not known, one of the family members, P5-1, was found previously
      to be specifically transcribed in lymphoid cells and tissue. In this study, we
      used computer programs Censor and RepeatMasker, and dot plot analysis to show
      that the major P5 family members are related in sequence to human endogenous
      retroviruses, HERV-L and HERV-16. The P5-HERV sequences have at least 60%
      sequence identity with HERV-L within the pol region but differ significantly
      within the gag and LTR regions. The LTRs flanking the P5-HERV sequences share
      about 70% identity with the repeat element LTR16B. Structural analysis of open
      reading frames (ORFs) confirmed that the P5-1 cDNA is characterized by many stop
      codons and short putative coding regions resembling the patterns found in the
      HERV-L nucleotide sequence rather than those found in an mRNA sequence such as
      expressed by HLA class I genes. A 159 base pair (bp) ORF at the 5' end of the
      2535 bp P5-1 mRNA may code for a peptide of 52 amino acids with a domain
      identical in sequence to the signal peptide of HLA molecules. Furthermore, the P5
      1 mRNA is complementary in sequence to retroviral pol mRNA. Therefore, the P5-1
      genomic sequence appears to be an example of an HERV within the MHC that
      expresses an antisense transcript with a possible role in immunity to retrovirus
      infection.

PMID- 10199915
TI  - Structural analysis, expression, and chromosomal localization of the mouse ikba
      gene.
AB  - The pleiotropic transcription factor NF-kappaB is localized in the cytoplasm
      bound to its inhibitory subunit IkappaB. The predominant form of NF-kappaB is a
      p50/p65 heterodimer which can be released from IkappaB-alpha and migrate to the
      nucleus. Previous studies have shown that IkappaB-alpha-/- mice die 8 to 10 days
      postnatally, showing runting and a severe dermatitis. However, the organ
      distribution of mouse IkappaB-alpha, the exon-intron structure, and the
      chromosomal localization of ikba have not been determined so far. A mouse Sv129
      genomic DNA library was screened with a human IkappaB-alpha/MAD-3 cDNA probe. One
      clone (P1) was isolated, spanning the complete ikba gene and the
      promoter/enhancer region. We show that the exon-intron structure between mouse
      and pig ikba is completely conserved. In contrast to human ikba, the ankyrin
      repeat 5 is not interrupted by an intron. Furthermore, the mouse ikba promoter
      contains 6 putative NF-kappaB binding sequences, which are conserved in mouse,
      pig, and human, underlining the importance of NF-kappaB as a key regulator of
      ikba transcription. The deduced amino acid sequence shows >90% similarity between
      mouse, pig, and human ikba. Chromosome mapping localized the mouse ikba gene to
      chromosome 12. Northern blot analysis demonstrated predominant expression in
      lymphoid tissue (lymph node and thymus). However, IkappaB-alpha mRNA was detected
      as well in liver tissue, the gastrointestinal tract, and the reproductive tract.
      The cloning and determination of the structure are a prerequisite for the
      construction of vectors for conditional gene targeting experiments.

PMID- 10199917
TI  - Nackt (nkt), a new hair loss mutation of the mouse with associated CD4
      deficiency.
AB  - A spontaneous recessive mutation named nackt (symbol: nkt) affecting hair growth
      and T-cell development was discovered in a moderately inbred stock of mice. Skin
      lesions were characterized by sparse rough coat, bare patches around the eyes and
      neck, and a scratching behavior throughout life. Fluorescence-activated cell
      sorter analysis indicated a deficiency in the CD4(+) 8(-) T-cell subset in the
      thymus and a marked decrease in CD4(+) T cells in peripheral lymphoid organs.
      Linkage analysis using a set of molecular markers and an F2 intersubspecific
      cross indicated that the mutation maps to the central region of mouse chromosome
      13, in a region homologous to human chromosome 5q22-q35.

PMID- 10199919
TI  - Characterization of Mhc-DRB allelic diversity in white-tailed deer (Odocoileus
      virginianus) provides insight into Mhc-DRB allelic evolution within Cervidae.
AB  - Although white-tailed deer (Odocoileus virginianus) are one of North America's
      best studied mammals, no information is available concerning allelic diversity at
      any locus of the major histocompatibility complex in this taxon. Using the
      polymerase chain reaction, single-stranded conformation polymorphism analysis,
      and DNA sequencing techniques, 15 DRB exon 2 alleles were identified among 150
      white-tailed deer from a single population in southeastern Oklahoma. These
      alleles represent a single locus and exhibit a high degree of nucleotide and
      amino acid polymorphism, with most amino acid variation occurring at positions
      forming the peptide binding sites. Furthermore, twenty-seven amino acid residues
      unique to white-tailed deer DRB alleles were detected, with 19 of these occurring
      at residues forming contact points of the peptide binding region. Significantly
      higher rates of nonsynonymous than synonymous substitutions were detected among
      these DRB alleles. In contrast to other studies of Artiodactyla DRB sequences,
      interallelic recombination does not appear to be playing a significant role in
      the generation of allelic diversity at this locus in white-tailed deer. To
      examine evolution of white-tailed deer (Odvi-DRB) alleles within Cervidae, we
      performed a phylogenetic analysis of all published red deer (Ceel-DRB), roe deer
      (Caca-DRB), and moose (Alal-DRB) DRB alleles. The phylogenetic tree clearly shows
      a trans-species persistence of DRB lineages among these taxa. Moreover, this
      phylogenetic tree provides insight into evolution of DRB allelic lineages within
      Cervidae and may aid in assignment of red deer DRB alleles to specific loci.

PMID- 10199918
TI  - Cloning and chromosomal mapping of a gene isolated from thymic stromal cells
      encoding a new mouse type II membrane serine protease, epithin, containing four
      LDL receptor modules and two CUB domains.
AB  - We cloned and sequenced a mouse gene encoding a new type of membrane bound serine
      protease (epithin) containing a multidomain structure. The initial cDNA clone was
      found previously in a polymerase chain reaction (PCR)-based subtractive library
      generated from fetal thymic stromal cells, and the message was shown to be highly
      expressed in a thymic epithelial nurse cell line. A clone isolated from a severe
      combined immunodeficiency (SCID) thymus library and extended to its full length
      at the 5' end with the RACE technique contains an open reading frame of 902 amino
      acids. Based on the sequence of this clone, the predicted protein structure is a
      type II membrane protein with a C-terminal serine protease domain linked to the
      membrane by four low density lipoprotein receptor modules and two CUB domains.
      High message expression by northern blotting was detected in intestine, kidney,
      lung, SCID, and Rag-2(-/-) thymus, and 2-deoxyguanosine-treated fetal thymic
      rudiment, but not in skeletal muscle, liver, heart, testis, and brain. Sorted MHC
      class II+ and II- fetal thymic stromal cells were positive for expression by
      reverse transcriptase-PCR, whereas CD45(+) thymocytes were not. The gene was
      found in chicken and multiple mammalian species under low stringency Southern
      hybridization conditions. Under high stringency conditions, only a single gene
      per haploid genome was identified in the mouse. This gene, Prss14 (protease,
      serine, 14), was mapped to mouse chromosome 9 and is closely linked to the Fli1
      (Friend leukemia integration 1) gene.

PMID- 10199920
TI  - Organization of the genes encoding the human proteasome activators PA28alpha and
      beta.
AB  - Two proteasome activators PA28alpha and beta, which have been implicated in
      antigen processing for loading class I MHC molecules, are synthesized in response
      to Ifn-gamma. The human genes encoding these activators (PSME1 and PSME2,
      respectively) were analyzed by sequencing. Each gene comprised 11 exons,
      consistent with gene duplication during vertebrate evolution. The intron/exon
      organization of both genes was highly conserved, the major difference being the
      absence of the exon encoding the lysine and glutamic acid-rich 'KEKE' motif in
      PA28beta. Two other genes of relevance to the immune system were located close to
      those for PA28 at 14q11.2 including ISGF3G, a protein involved in transcription
      after IFNalpha signalling. These sequences were also characterized.

PMID- 10199921
TI  - Gene conversion of major histocompatibility complex genes is associated with CpG
      rich regions.
AB  - We examined 32 DNA sequences of mouse and human major histocompatibility complex
      (MHC) genes believed to have been subjected to gene conversion events. All
      regions of the mouse H2 genes as well as the human HLA genes which have been
      implied to be involved in gene conversion events had elevated levels of CpG
      dinucleotides, whereas the rest of the genes showed extensive CpG suppression.
      Mouse MHC genes which have been suspected but not directly implied to be involved
      in gene conversion events also showed elevated levels of CpG dinucleotides.
      Moreover, both mouse and human MHC genes which have never been suspected of
      undergoing gene conversion had low levels of CpG throughout the genes. These
      results indicate that high CpG levels are correlated with gene conversion rather
      than with polymorphism, as non-polymorphic genes that have been implicated as
      gene conversion donors also have elevated levels of CpG dimers in the involved
      regions, whereas polymorphic genes which have never been considered to undergo
      gene conversion events have a low level of CpG dinucleotides. We also studied the
      methylation pattern of CpG dimers in the Abk gene by restriction enzyme digestion
      of mouse testis DNA followed by Southern blot and hybridization to an Abk
      specific probe. The examined CpG dimers in prepubescent mice, where the latest
      germline stages are spermatogonia, leptene, or pachytene, are respectively non
      methylated. Accordingly, the CpG dimers appear to be non-methylated in germline
      DNA from the testis of prepubescent mice, where gene conversions have been
      reported to occur.

PMID- 10199922
TI  - Multiple class I loci expressed by the quail Mhc.

PMID- 10199923
TI  - Identification and sequence analysis of an Mhc class II B gene in a marsupial
      (Monodelphis domestica).

PMID- 10199924
TI  - Conservation of 3' untranslated region elements in tammar wallaby (Macropus
      eugenii) TNF-alpha mRNA.

PMID- 10199925
TI  - The sequence and organization of the mouse valyl-tRNA synthetase gene G7a/Bat6
      located in the MHC class III region.

PMID- 10199926
TI  - Lymphoscintigraphy in oncology: a rediscovered challenge.
AB  - The validation of the sentinel node concept in oncology has led to the
      rediscovery of lymphoscintigraphy. By combining preoperative lymphatic mapping
      with intraoperative probe detection this nuclear medicine procedure is being
      increasingly used to identify and detect the sentinel node in melanoma, breast
      cancer, and in other malignancies such as penile cancer and vulvar cancer. In the
      past lymphoscintigraphy has been widely applied for various indications in
      oncology, and in the case of the internal mammary lymph-node chain its current
      use in breast cancer remains essential to adjust irradiation treatment to the
      individual findings of each patient. In another diagnostic area,
      lymphoscintigraphy is also useful to document altered drainage patterns after
      surgery and/or radiotherapy; its use in breast cancer patients with upper limb
      oedema after axillary lymph-node dissection or in melanoma patients with lower
      extremity oedema after groin dissection can provide information for physiotherapy
      or reconstructive surgery. Finally, the renewed interest in lymphoscintigraphy in
      oncology has led not only to the rediscovery of findings from old literature
      reports, but also to a discussion about methodological aspects such as tracer
      characteristics, image acquisition or administration routes, as well as to
      discussion on the study of migration patterns of radiolabelled colloid particles
      in the context of cancer dissemination. All this makes the need for standardized
      guidelines for lymphoscintigraphy mandatory.

PMID- 10199927
TI  - Lymphatic mapping and sentinel lymph node biopsy in breast cancer.
AB  - Lymphatic mapping with selective lymphadenectomy is an attractive approach in
      breast-cancer patients. It uses existing technology to exploit logical anatomic
      and physiological principles to identify occult regional lymph-node metastases.
      The lymphatic flow is visualized and the first (sentinel) lymph node on a direct
      drainage pathway from the primary tumour is identified. This is the node at
      greatest risk of harbouring metastatic deposits. Retrieving this node requires a
      concerted effort from the nuclear medicine physician, surgeon and pathologist.
      Lymphoscintigraphy can indicate the number of sentinel nodes and their location.
      The surgeon can use two techniques to find the node. A vital dye injected at the
      tumour site will stain the lymphatic duct as well as the sentinel node and allow
      their visual identification. Alternatively, a lymph-node-seeking
      radiopharmaceutical will also migrate from the tumour site to the sentinel node
      and will enable its retrieval with the use of a gamma detection probe. The
      pathologist has a number of techniques to identify tumour deposits in the lymph
      node. A review of the literature shows that the sentinel node can be found in
      more than 90% of the patients. With experience, the false-negative rate can be
      kept down to about 5%. This novel approach of lymphatic mapping with selective
      lymphadenectomy may lead to a substantial reduction in the need for axillary node
      dissection in patients with breast cancer without compromising survival and
      regional control, and without loss of prognostic and staging information. This
      development will translate into a great reduction in patient morbidity and
      medical expenses.

PMID- 10199928
TI  - The sentinel node in breast cancer: implications for adjuvant treatment?

PMID- 10199929
TI  - The sentinel node procedure in cutaneous melanoma: an overview of 6 years'
      experience.

PMID- 10199930
TI  - Clinical applications of gamma-detection probes - radioguided surgery.
AB  - Radioguided surgery (RGS) is a surgical technique that enables the surgeon to
      identify tissue "marked" by a radionuclide before surgery, based on the tissue
      characteristics, the radioactive tracer and its carrying molecule, or the
      affinity of both. Thus, yet another tool has been added to the inspection and
      palpation traditionally used by the surgeon. Current clinical applications of
      radioguided surgery are: radioimmunoguided surgery (RIGS) for colon cancer,
      sentinel-node mapping for malignant melanoma (which has become state-of-the-art),
      sentinel-node mapping for breast, vulvar and penile cancer, and detection of
      parathyroid adenoma and bone tumour (such as osteid osteoma). Although the same
      gamma-detecting probe (GDP) may be used for all these applications, the carrier
      substance and the radionuclide differ. MoAb and peptides are used for RIGS,
      sulphur colloid for sentinel-node mapping, iodine-125 for RIGS, technetium-99m
      for sentinel node, parathyroid and bone. The mode of injection also differs, but
      there are some common principles of gamma-guided surgery. RIGS enables the
      surgeon to corroborate tumour existence, find occult metastases, and assess the
      margins of resection; this may result in a change on the surgical plan. Sentinel
      lymph-node (SLN) scintigraphy for melanoma guides the surgeon to find the
      involved lymph nodes for lymph-node dissection. SLN for breast cancer is being
      investigated with promising results. This procedure has also changed the outlook
      of lymph-node pathology by giving the pathologist designated tissue samples for
      more comprehensive examination. Gamma-guided surgery will result in more accurate
      and less unnecessary surgery, better pathology and, hopefully, in better patient
      survival.

PMID- 10199931
TI  - Radiopharmaceuticals in sentinel lymph-node detection - an overview.
AB  - Biopsy of the first tumour-draining lymph node (sentinel node, SN) is bound to
      become the procedure of choice in regional staging of melanoma and breast cancer
      patients. Several radiopharmaceuticals have been developed for
      lymphoscintigraphy. In this paper we review the most frequently used
      radiopharmaceuticals for their appropriateness in the sentinel-node procedure. We
      conclude that accurate localization of SNs is demonstrated using technetium-99m
      sulfur colloid (99mTc-SC), 99mTc antimony trisulfide colloid (99mTc-ATC) [10] and
      99mTc nanocolloidal albumin (99mTc-CA). 99mTc-Ca and 99mTc-SC are both available
      in Europe. In the United States 99mTc-SC is the only registered tracer for
      lymphoscintigraphy.

PMID- 10199932
TI  - Pathological investigation of sentinel lymph nodes.
AB  - The sentinel lymph-node procedure enables selective targeting of the first
      draining lymph node, where the initial metastases will form. A negative sentinel
      node (SN) predicts the absence of tumour metastases in the other regional lymph
      nodes with high accuracy. This means that in the case of a negative SN, regional
      lymph-node dissection is no longer necessary. Besides saving costs, this will
      prevent many side-effects as a result of lymph-node dissection. The task of the
      pathologist is to screen SNs for metastases. To this end, several techniques are
      available such as standard histo- and cytopathological techniques,
      immunohistochemistry, flow cytometry, and molecular biological techniques. These
      methods are explained and their sensitivity for detecting SN metastases is
      discussed. Some of these techniques also appear to be useful for intra-operative
      evaluation of SNs. The standard protocol for detection of SN metastases consists
      of extensive histopathological investigation including step H&E stained sections
      and immunohistochemistry. Intra-operative frozen-section analysis of SNs has been
      shown to be reliable for breast-cancer axillary lymph nodes. In the intra
      operative setting, imprint cytology can also be used but its additional value to
      frozen section analysis is not yet clear. Further studies are necessary to
      establish the role of sophisticated molecular biological techniques such as
      reverse transcription polymerase chain reaction (RT-PCR) in detecting SN
      metastases. The sensitivity of flow cytometry is too low for this purpose.

PMID- 10199933
TI  - Examining the immune response in sentinel lymph nodes of mice and men.
AB  - Recently, it was recognized that an immune response develops along one of two
      major pathways. One leads to a destructive immune response (type 1), while the
      alternative leads to a nondestructive immune response (type 2). Our studies in
      animal models suggest that therapeutic vaccines induce a tumor-specific type 1
      immune response while ineffective vaccines induce a type 2 response. These
      results have led us to examine the immune response in sentinel lymph nodes
      draining tumor vaccines of patients entered onto clinical trials for melanoma,
      breast and renal cell cancer.

PMID- 10199934
TI  - Lessons for medicine and nuclear medicine research.

PMID- 10199935
TI  - The evaluation and calibration of fan-beam collimators.
AB  - The aims of this study were (a) to determine the true focal length of a fan-beam
      collimator and (b) to calibrate image size (mm/pixel) for each collimator to
      permit inter-comparison of image data acquired on different gamma camera systems.
      A total of six fan-beam collimators on three dual-head gamma camera systems were
      evaluated using a set of four cobalt-57 point source markers. The markers were
      arranged in a line in the transverse plane with a known separation between them.
      Tomographic images were obtained at three radii of rotation. From reconstructed
      transaxial images the distance between markers was measured in pixels and used to
      determine pixel size in mm/pixel. The system value for the focal length of the
      collimator was modified by up to +/-100 mm and transaxial images were again
      reconstructed. To standardize pixel size between systems, the apparent radius of
      rotation during a single-photon emission tomography (SPET) acquisition was
      modified by changes to the effective collimator thickness. SPET images of a 3D
      brain phantom were acquired on each system and reconstructed using both the
      original and the modified values of collimator focal length and thickness. Co
      registration and subtraction of the reconstructed transaxial images was used to
      evaluate the effects of changes in collimator parameters. Pixel size in the
      reconstructed image was found to be a function of both the radius of rotation and
      the focal length. At the correct focal length, pixel size was essentially
      independent of the radius of rotation. For all six collimators, true focal length
      differed from the original focal length by up to 26 mm. These differences in
      focal length resulted in up to 6% variation in pixel size between systems. Pixel
      size between the three systems was standardized by altering the value for
      collimator thickness. Subtraction of the co-registered SPET images of the 3D
      brain phantom was significantly improved after optimization of collimator
      parameters, with a 35%-50% reduction in the standard deviation of residual counts
      in the subtraction images. In conclusion, we have described a simple method for
      measurement of the focal length of a fan-beam collimator. This is an important
      parameter on multidetector systems for optimum image quality and where accurate
      co-registration of SPET to SPET and SPET to MRI studies is required.

PMID- 10199936
TI  - Deposition of aqueous aerosol of technetium-99m diethylene triamine penta-acetic
      acid generated and delivered by a novel system (AERx) in healthy subjects.
AB  - Deposition of technetium-99m diethylene triamine penta-acetic acid aqueous
      radioaerosols generated by a novel aerosol delivery system (AERx) was studied in
      six healthy subjects using both planar and single-photon emission tomography
      (SPET) imaging. AERx is a microprocessor-controlled, bolus inhalation device that
      is actuated at pre-programmed values of inspiratory flow rate and volume. The
      aims of the study were to determine the effects of posture and inhaled volume
      upon deposition of the aerosol in the lungs. Each subject inhaled the
      radioaerosol in two positions (supine vs sitting) and with two inspiratory
      manoeuvres [vital capacity (VC) vs "fixed volume" of 1 l above functional
      residual capacity]. Simultaneous transmission-emission planar and tomographic
      images were acquired. The results showed diffuse deposition of the aerosol in the
      lung. Neither the breathing manoeuvre nor the posture was found to affect the
      distribution of the aerosol as measured by the ratio of the activity (counts per
      pixel) in the peripheral:central (penetration index, PI) or in the apex:base
      regions of the planar lung images (P>0.1). A small, albeit statistically
      significant, difference in PI (P<0.03) was found between VC and fixed volume
      sitting manoeuvres with SPET only. The PI values themselves indicate that the
      radioaerosol was well distributed in the lung, with the periphery having 45%-64%
      of the activity of the central region. Superposition of transmission SPET lung
      outline on emission SPET visually confirmed the excellent peripheral deposition
      of the aerosol. The AERx system showed high efficiency of delivery, with
      approximately 50% of the extruded dose in the device depositing in the lung. The
      uniformity of radioactivity distributed throughout the lung is attributed to the
      fine particle size (mass median aerodynamic diameter of 2 microm) of the aerosol
      and the electronic control of aerosol inhalation by the device. In conclusion,
      the AERx system can be ideal for diffuse aerosol deposition of therapeutic or
      diagnostic agents and is largely unaffected by inhaled volume and posture. The
      efficiency of the device device can limit the total radiation exposure of
      patients and staff administering the radioaerosols, and can make it suitable for
      delivery of expensive drugs.

PMID- 10199937
TI  - Protein synthesis rate measured with L-[1-11C]tyrosine positron emission
      tomography correlates with mitotic activity and MIB-1 antibody-detected
      proliferation in human soft tissue sarcomas.
AB  - Protein synthesis rate (PSR) can be assessed in vivo using positron emission
      tomography with L-[1-11C]tyrosine (TYR-PET). Biological activity of soft tissue
      sarcomas (STS) can be measured in vitro by the mitotic rate and number of
      proliferating cells. In STS the grade of malignancy, in which the mitotic index
      plays a major role, is considered to be the major standard in predicting
      biological tumour behaviour. This study was designed to test the validity of TYR
      PET in relation to different histopathological features. In 21 patients with
      untreated STS, the PSR was measured using TYR-PET. The number of mitoses was
      counted and tumours were graded according to the grading system of Coindre et al.
      (Cancer 1986; 58:306-309). Proliferative activity was assessed by
      immunohistological detection of the Ki-67 nuclear antigen using MIB-1 monoclonal
      antibody. To test the association between the PSR and these tumour parameters, a
      correlation analysis was performed. A significant (P<0.05) correlation was found
      between PSR and the Ki-67 proliferation index (R = 0.54), and between PSR and
      mitotic rate (R = 0.64). There was no correlation between PSR and tumour grade.
      The present study in malignant soft tissue tumours relates in vivo tumour
      metabolism as established with TYR-PET to tumour activity measured in vitro and
      indicates that the non-invasive method of TYR-PET can estimate the mitotic and
      proliferative activity in STS.

PMID- 10199938
TI  - Uptake of positron emission tomography tracers in experimental bacterial
      infections: a comparative biodistribution study of radiolabeled FDG, thymidine, L
      methionine, 67Ga-citrate, and 125I-HSA.
AB  - The purpose of this study was to evaluate the localization of positron emission
      tomography (PET) tracers [2-deoxy-2-fluoro-D-glucose (FDG), thymidine, and L
      methionine] in sites of bacterial infection, and to contrast this with that of
      other tracers. The left calf muscles of rats were infected with a suspension of
      Escherichia coli and the biodistribution of 18F- or 3H-FDG, 3H-thymidine, L-11C-
      or 3H-methionine, gallium-67 citrate (67Ga-citrate) and iodine-125 human serum
      albumin (125I-HSA) was determined in these animals. 3H-FDG uptake in the
      infectious foci was evaluated by autoradiography of histological sections.
      Although 18F-FDG, 67Ga-citrate, and 125I-HSA showed comparatively high uptake in
      the infected muscle [the percentage activity of injected dose (ID) per gram of
      tissue normalized for rat weight in kilogram (%ID/g)xkg at 2 h postinjection was
      as follows: 18F-FDG, 0.184+/-0.026 to 0.218+/-0.046; 67Ga-citrate, 0.221+/-0.016;
      125I-HSA, 0. 198+/-0.019], the infected muscle to blood ratio was much higher for
      18F-FDG than for 67Ga-citrate or 125I-HSA (18F-FDG, 10.31+/-0.76 to 14.89+/-2.26;
      67Ga-citrate, 1.24+/-0.67; 125I-HSA, 0.20+/-0.02). The draining reactive lymph
      nodes also showed higher accumulation of 18F-FDG than of 67Ga-citrate or 125I
      HSA. The uptake of 3H-thymidine and L-11C- or 3H-methionine in the infected
      muscle was lower than that of 18F- or 3H-FDG (at 2 h postinjection, 3H-thymidine
      = 0. 039+/-0.005 and L-3H-methionine = 0.063+/-0.007 (%ID/g)xkg. Autoradiographs
      showed that the highest 3H-FDG uptake was seen in the area of inflammatory cell
      infiltration surrounding the necrotic region. In conclusion, 18F-FDG, which
      rapidly accumulates in sites of bacterial infection and in reactive lymph nodes
      with a high target to background ratio, appears to be a promising infection
      detection agent.

PMID- 10199939
TI  - In vivo imaging of serotonin transporters with [99mTc]TRODAT-1 in nonhuman
      primates.
AB  - [99mTc]TRODAT-1 was the first 99mTc-labeled imaging agent to show specific
      binding to dopamine transporters (DAT) in the striatum (STR) of human brain.
      Additionally, in vitro binding and autoradiographic experiments demonstrated that
      this tracer also binds to serotonin transporters (SERT) in the
      midbrain/hypothalamus (MB) area. In this study, [99mTc]TRODAT-1 was investigated
      as a potentially useful ligand to image SERT in the MB of living brain. A total
      of eight single-photon emission tomography (SPET) scans were performed in two
      baboons (Papio anubis) after intravenous (i.v.) injection of 740 MBq (20 mCi) of
      [99mTc]TRODAT-1 using a triple-head gamma camera equipped with ultra-high
      resolution fan-beam collimators (scan time: 0-210 min). In four blocking studies,
      baboons were pretreated with (+)McN5652 (1 mg/kg, i.v.) or methylphenidate (1
      mg/kg, i.v.) to specifically block SERT or DAT, respectively. After co
      registration with magnetic resonance images of the same baboon, a region of
      interest analysis was performed using predefined templates to calculate specific
      uptake in the midbrain area and the striatum, with the cerebellum as the
      background region [(MB-CB)/CB, (STR-CB)/CB]. Additionally, two PET scans of the
      same baboons were performed after i.v. injections of 74-111 MBq (2-3 mCi) of
      [11C](+)McN5652 to identify the SERT sites. In [99mTc]TRODAT-1/SPET scans, the
      SERT sites in the MB region were clearly visualized. Semiquantitative analysis
      revealed a specific uptake in MB ([MB-CB]/CB) of 0.30+/-0.02, which was decreased
      to 0. 040+/-0.005 after pretreatment with nonradioactive (+)McN5652, a selective
      SERT ligand. Pretreatment with methylphenidate reduced the specific binding of
      [99mTc]TRODAT-1 to DAT sites [(STR-CB)/CB] from 2.45+/-0.13 to 0.32+/-0.04
      without any effect on its binding to SERT sites [(MB-CB)/CB], which was confirmed
      by the co-registration of the [11C](+)McN5652/PET scans. This preliminary study
      suggests that specific binding of [99mTc]TRODAT-1 to SERT sites can be detected
      by in vivo SPET imaging despite the low target to background ratio. These
      findings provide impetus for further development of similar compounds with
      improved binding affinity and selectivity to SERT sites.

PMID- 10199940
TI  - Antibody-guided three-step therapy for high grade glioma with yttrium-90 biotin.
AB  - While the incidence of brain tumours seems to be increasing, median survival in
      patients with glioblastoma remains less than 1 year, despite improved diagnostic
      imaging and neurosurgical techniques, and innovations in treatment. We have
      developed an avidin-biotin pre-targeting approach for delivering therapeutic
      radionuclides to gliomas, using anti-tenascin monoclonal antibodies, which seems
      potentially effective for treating these tumours. We treated 48 eligible patients
      with histologically confirmed grade III or IV glioma and documented residual
      disease or recurrence after conventional treatment. Three-step radionuclide
      therapy was performed by intravenous administration of 35 mg/m2 of biotinylated
      anti-tenascin monoclonal antibody (1st step), followed 36 h later by 30 mg of
      avidin and 50 mg of streptavidin (2nd step), and 18-24 h later by 1-2 mg of
      yttrium-90-labelled biotin (3rd step). 90Y doses of 2.22-2.96 GBq/m2 were
      administered; maximum tolerated dose (MTD) was determined at 2.96 GBq/m2. Tumour
      mass reduction (>25%-100%), documented by computed tomography or magnetic
      resonance imaging, occurred in 12/48 patients (25%), with 8/48 having a duration
      of response of at least 12 months. At present, 12 patients are still in
      remission, comprising four with a complete response, two with a parital response,
      two with a minor response and four with stable disease. Median survival from 90Y
      treatment is 11 months for grade IV glioblastoma and 19 months for grade III
      anaplastic gliomas. Avidin-biotin based three-step radionuclide therapy is well
      tolerated at the dose of 2.2 GBq/m2, allowing the injection of 90Y-biotin without
      bone marrow transplantation. This new approach interferes with the progression of
      high-grade glioma and may produce tumour regression in patients no longer
      responsive to other therapies.

PMID- 10199941
TI  - Uptake kinetics of the somatostatin receptor ligand [86Y]DOTA-DPhe1- Tyr3
      octreotide ([86Y]SMT487) using positron emission tomography in non-human primates
      and calculation of radiation doses of the 90Y-labelled analogue.
AB  - [90Y]DOTA-DPhe1-Tyr3-octreotide ([90Y]-SMT487) has been suggested as a promising
      radiotherapeutic agent for somatostatin receptor-expressing tumours. In order to
      quantify the in vivo parameters of this compound and the radiation doses
      delivered to healthy organs, the analogue [86Y]DOTA-DPhe1-Tyr3-octreotide was
      synthesised and its uptake measured in baboons using positron emission tomography
      (PET). [86Y]DOTA-DPhe1-Tyr3-octreotide was administered at two different peptide
      concentrations, namely 2 and 100 microg peptide per m2 body surface. The latter
      concentration corresponded to a radiotherapeutic dose. In a third protocol
      [86Y]DOTA-DPhe1-Tyr3-octreotide was injected in conjunction with a simultaneous
      infusion of an amino acid solution that was high in l-lysine in order to lower
      the renal uptake of radioyttrium. Quantitative whole-body PET scans were recorded
      to measure the uptake kinetics for kidneys, liver, lung and bone. The individual
      absolute uptake kinetics were used to calculate the radiation doses for [90Y]DOTA
      DPhe1-Tyr3-octreotide according to the MIRD recommendations extrapolated to a 70
      kg human. The highest radiation dose was received by the kidneys, with 2.1-3.3
      mGy per MBq [90Y]DOTA-DPhe1-Tyr3-octreotide injected. For the 100 microg/m2
      SMT487 protocol with amino acid co-infusion this dose was about 20%-40% lower
      than for the other two treatment protocols. The liver and the red bone marrow
      received doses ranging from 0.32 to 0.53 mGy and 0.03 to 0.07 mGy per MBq
      [90Y]DOTA-DPhe1-Tyr3-octreotide, respectively. The average effective dose
      equivalent amounted to 0. 23-0.32 mSv/MBq. The comparatively low estimated
      radiation doses to normal organs support the initiation of clinical phase I
      trials with [90Y]DOTA-DPhe1-Tyr3-octreotide in patients with somatostatin
      receptor-expressing tumours.

PMID- 10199942
TI  - Evaluation of flow characteristics of soft-tissue vascular malformations using
      technetium-99m labelled red blood cells.
AB  - The estimation of intralesional haemodynamics is crucial in determining
      appropriate treatment for soft-tissue vascular malformations. The aim of this
      study was to develop a method to evaluate the flow characteristics of soft-tissue
      vascular malformations using technetium-99m labelled red blood cells (99mTc
      RBCs). Seventy-nine soft-tissue vascular malformations, including 20
      arteriovenous malformations and 59 venous malformations, in 57 patients were
      examined. Following the intravenous injection of 99mTc-RBCs, dynamic imaging was
      performed for 30 min with the lesion in the field of view (99mTc-RBC flow study).
      A time-activity curve was generated for the lesion, and the lesion was
      categorized as a high-flow or low-flow lesion by visual inspection of the curve.
      In low-flow lesions, mean vascular transit time (MTT) was calculated by curve
      fitting based on a two-compartment model. Twenty-nine lesions in 19 patients were
      examined twice, and reproducibility was assessed. In 23 venous malformations in
      16 patients, 99mTc-Sn colloid was percutaneously injected into the intravascular
      space of the lesion, and dynamic data of 5-min duration were acquired (direct
      puncture scintigraphy). MTT was estimated from the washout curve and compared
      with MTT estimated by 99mTc-RBC flow study. 99mTc-RBC flow study classified all
      20 arteriovenous malformations as high-flow lesions and all 59 venous
      malformations as low-flow lesions. In the low-flow lesions, MTT estimated by
      99mTc-RBC flow study ranged from 61.2 to 2174.9 s. In the reproducibility study,
      complete concordance in classification and high correlation in MTT were shown
      between the first and second examinations. MTT estimated by 99mTc-RBC flow study
      was significantly correlated with that estimated by direct puncture scintigraphy.
      In summary, 99mTc-RBC flow study provides a quantitative indicator of
      intralesional haemodynamics in low-flow lesions in addition to accurate
      distinction between high-flow and low-flow lesions. The results of this study
      suggest the feasibility of detailed evaluation of flow characteristics in soft
      tissue vascular malformations using 99mTc-RBCs.

PMID- 10199943
TI  - Determination of the gastric emptying of solid dosage forms using gamma
      scintigraphy: a problem of image timing and mathematical analysis.
AB  - This work was designed to identify the maximum time interval of image acquisition
      by gamma-scintigraphy for monitoring the emptying of a dosage form such as a
      tablet. Appropriate statistical parameters to describe this process were sought,
      including a statistical procedure for group comparisons of such data. Gamma
      scintigraphy was employed in seven healthy male volunteers, who swallowed a light
      and a dense tablet, each 12 mm in diameter, formulated to contain different
      isotopes to allow identification. Images were taken sequentially at 30-s
      intervals to provide images of each tablet in 1-min spacing until emptying of
      both tablets was reported. In selecting images, it was also possible to simulate
      image acquisition intervals of 2, 3, 5, 10, 15, 20 and 30 min. The values derived
      are discrete random variables. The maximum time interval between image
      acquisitions that permitted reliable results to be obtained was found to be 3 min
      for light and 2 min for dense tablets. Consideration of the emptying of a tablet
      as a Bernoulli random event provided a suitable statistical approach to the
      analysis of such data, giving a median and an interquartile range. While the
      commonly applied method, which is based on parametric procedures deriving
      arithmetic means and standard deviations, failed to detect a difference in the
      emptying times of the two types of tablets, the use of non-parametric statistics
      (Wilcoxon test) provided a clear distinction between them in this respect. The
      assessment of gastric emptying by gamma-scintigraphy studies can be improved by
      using short image intervals and application of appropriate statistical analysis.

PMID- 10199944
TI  - Comparison of FDG PET and positron coincidence detection imaging using a dual
      head gamma camera with 5/8-inch NaI(Tl) crystals in patients with suspected body
      malignancies.
AB  - The purpose of this study was to compare the diagnostic accuracy of fluorine-18
      fluorodeoxyglucose (FDG) images obtained with (a) a dual-head coincidence gamma
      camera (DHC) equipped with 5/8-inch-thick NaI(Tl) crystals and parallel slit
      collimators and (b) a dedicated positron emission tomograph (PET) in a series of
      28 patients with known or suspected malignancies. Twenty-eight patients with
      known or suspected malignancies underwent whole-body FDG PET imaging (Siemens,
      ECAT 933) after injection of approximately 10 mCi of 18F-FDG. FDG DHC images were
      then acquired for 30 min over the regions of interest using a dual-head gamma
      camera (VariCam, Elscint). The images were reconstructed in the normal mode,
      using photopeak/photopeak, photopeak/Compton, and Compton/photopeak coincidence
      events. FDG PET imaging found 45 lesions ranging in size from 1 cm to 7 cm in 28
      patients. FDG DHC imaging detected 35/45 (78%) of these lesions. Among the ten
      lesions not seen with FDG DHC imaging, eight were less than 1.5 cm in size, and
      two were located centrally within the abdomen suffering from marked attenuation
      effects. The lesions were classified into three categories: thorax (n=24), liver
      (n=12), and extrahepatic abdominal (n=9). FDG DHC imaging identified 100% of
      lesions above 1.5 cm in the thorax group and 78% of those below 1.5 cm, for an
      overall total of 83%. FDG DHC imaging identified 100% of lesions above 1.5 cm, in
      the liver and 43% of lesions below 1.5 cm, for an overall total of 67%. FDG DHC
      imaging identified 78% of lesions above 1.5 cm in the extrahepatic abdominal
      group. There were no lesions below 1.5 cm in this group. FDG coincidence imaging
      using a dual-head gamma camera detected 90% of lesions greater than 1.5 cm. These
      data suggest that DHC imaging can be used clinically in well-defined diagnostic
      situations to differentiate benign from malignant lesions.

PMID- 10199945
TI  - Imaging of lung cancer with fluorine-18 fluorodeoxyglucose: comparison of a dual
      head gamma camera in coincidence mode with a full-ring positron emission
      tomography system.
AB  - Dual-head gamma cameras operated in coincidence mode are a new approach for
      tumour imaging using fluorine-18 fluorodeoxyglucose (FDG). The aim of this study
      was to assess the diagnostic accuracy of such a camera system in comparison with
      a full-ring positron emission tomography (PET) system in patients with lung
      cancer. Twenty-seven patients (1 female, 26 males, age 62+/-9 years) with lung
      cancer or indeterminate pulmonary nodules were studied on the same day with a
      full-ring PET scanner (Siemens ECAT EXACT) and a coincidence gamma camera system
      (ADAC Vertex MCD). Sixty minutes after injection of 185-370 MBq FDG, a scan of
      the chest was performed with the full-ring system. Approximately 2 h p.i., the
      coincidence camera study was performed. Coincidence gamma camera (CGC) and PET
      images with (PETac) and without attenuation correction (PETnac) were analysed
      independently by two blinded observers. In addition, FDG uptake in primary
      tumours and involved lymph nodes was quantified relative to normal contralateral
      lung (T/L ratios). All primary tumours were histologically proven. The lymph node
      status was histologically determined in 23 patients. In four patients, no lymph
      node sampling was performed because of extensive disease or concurrent illnesses.
      In the 27 patients, 25 primary lung cancers and two metastatic lesions were
      histologically diagnosed. The number of coincidences per centimetre axial field
      of view was 3.33+/-0. 93x10(5) for the CGC and 1.09+/-0.36x10(6) for the
      dedicated PET system. All primary tumours (size: 4.6+/-2.6 cm) were correctly
      identified in the CGC and dedicated PET studies. T/L ratios were 4. 7+/-2.5 for
      CGC and 6.9+/-2.8 for PETnac (P <0.001). Histopathological evaluation revealed
      lymph node metastases in 11 of 88 sampled lymph node stations (size: 2.3+/-1.0
      cm). All lymph node metastases were identified in the PETac studies, while PETnac
      detected 10/11 and CGC 8/11. For positive lymph nodes that were visible in CGC
      and PETnac studies, T/L ratios were 3.7+/-2.3 for CGC and 6.6+/-3.1 for PETnac
      (P=0.02). The diameters of false-negative lymph nodes in the CGC studies were
      0.75, 1.5 and 2 cm. False-positive FDG uptake in lymph nodes was found in two
      patients with all three imaging methods. For all lesions combined, T/L ratios in
      CGC relative to PETnac studies decreased significantly with decreasing lesion
      size (r=0.62; P<0.001). In conclusion, compared with a full-ring PET system the
      sensitivity of CGC imaging for detection of lung cancer is limited by a lower
      image contrast which deteriorates with decreasing lesion size. Nevertheless, the
      ability of CGC imaging to detect pulmonary lesions with a diameter of at least 2
      cm appears to be similar to that of a full-ring system. Both systems provide a
      similar specificity for the evaluation of lymph node involvement.

PMID- 10199946
TI  - Technetium-99m sestamibi imaging in paediatric neuroblastoma and ganglioneuroma
      and its relation to P-glycoprotein.
AB  - Imaging with technetium-99m sestamibi offers a non-invasive approach to detect
      the presence of functional P-glycoprotein (Pgp), one of the major causes of
      multidrug resistance, in human malignancies. A clinical role for Pgp has been
      suggested in the subpopulation of primary neuroblastoma without amplification of
      the proto-oncogene MYCN. We wanted to evaluate the usefulness of 99mTc-sestamibi
      scintigraphy in the screening of neural crest tumours for the presence of Pgp. In
      ten children suffering from MYCN-negative neuroblastoma, ganglioneuroblastoma or
      ganglioneuroma, 99mTc-sestamibi imaging was performed at initial diagnosis. All
      patients underwent planar imaging 20-30 min and 3.5-4 h after intravenous
      injection of 740 MBq/1.73 m2 99mTc-sestamibi. Tumour to normal tissue ratios, as
      well as washout rates, were determined and compared with in vitro flow cytometric
      analysis of Pgp expression and function. Pgp expression was analysed flow
      cytometrically with the monoclonal antibodies 4E3 and MRK16, and Pgp function was
      evaluated by means of rhodamine 123 uptake and efflux either in the absence or in
      the presence of the Pgp inhibitor verapamil. In nine of ten patients, we found
      that the intratumoral 99mTc-sestamibi activity was comparable to the background
      activity, which might be suggestive of Pgp presence. This was confirmed flow
      cytometrically in all but one patient. 99mTc-sestamibi enhancement was seen in
      the primary tumour and the bone marrow metastases of one of the ten patients, and
      this result was concordant with a negative Pgp status. The findings presented
      suggest that 99mTc-sestamibi imaging results might correlate with the presence of
      functional Pgp in neural crest tumours without MYCN amplification.

PMID- 10199947
TI  - Altered gastric emptying in patients with irritable bowel syndrome.
AB  - Irritable bowel syndrome is the most frequent functional disorder of the
      digestive system. Patients with irritable bowel syndrome have motor disorders not
      only in the colon, but also in other parts of the digestive tract such as the
      oesophagus and small intestine; however, it is not known whether the stomach is
      also involved. We used a radiolabelled mixed solid-liquid meal (technetium-99m
      for the solid component, indium-111 for the liquid component) to study gastric
      emptying of solids (GES), liquids (GEL) and indigestible solids (GER) in 50
      patients diagnosed as having irritable bowel syndrome (30 with predominant
      constipation and 20 with predominant diarrhoea). GER was measured by counting the
      number of indigestible solids remaining in the stomach 4 h after they were
      swallowed. In patients with irritable bowel syndrome, GES and GEL were slower
      than in control subjects (P<0.05). GER was normal in all patients except for two
      women. Thirty-two patients (64%) showed delayed GES, 29 (58%) delayed GEL, and 2
      (4%) delayed GER. Among patients with irritable bowel syndrome, GES was slower in
      those with predominant constipation than in those with predominant diarrhoea
      (P<0.05); GEL and GER were similar in both groups. Gastroparesis was found in a
      large proportion of patients with irritable bowel syndrome, suggesting the
      presence of a more generalised motor disorder of the gut.

PMID- 10199948
TI  - Exercise-induced stunning continues for at least one hour: evaluation with
      quantitative gated single-photon emission tomography.
AB  - To elucidate the after-effect of exercise on left ventricular (LV) function, end
      diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (LVEF)
      were evaluated at 1 h after exercise and at rest by technetium-99m tetrofosmin
      gated myocardial single-photon emission tomography (SPET) using an automated
      program in 53 subjects. The subjects were grouped as follows: normal scan (n =
      16), ischaemia (n = 19) and infarction (n = 18), based on the interpretation of
      perfusion images. Postexercise LVEF did not differ from resting LVEF in the
      groups with normal scan and infarction. In patients with ischaemia, postexercise
      EDV (90+/-17 ml, mean +/-SD) and ESV (44+/-15 ml) were significantly higher than
      EDV (84+/-15 ml, P = 0.001) and ESV (36+/-14 ml, P<0.0005) at rest. LVEF was
      significantly depressed 1 h after exercise (53%+/-9% vs 58%+/-9%, P<0.0001). In
      ischaemic patients with depressed postexercise LVEF, LVEF difference between rest
      and postexercise showed a significant correlation with the sum of defect scores,
      which were reversible from exercise to rest perfusion images (r = 0.92,
      P<0.0001). These results indicate that exercise-induced LV dysfunction
      (myocardial stunning) continues for at least 1 h in ischaemic patients and that
      the extent of LVEF depression is determined by the severity of ischaemia.

PMID- 10199949
TI  - Cardiac sympathetic denervation in familial amyloid polyneuropathy assessed by
      iodine-123 metaiodobenzylguanidine scintigraphy and heart rate variability.
AB  - Familial amyloid polyneuropathy (FAP) is a rare and severe hereditary form of
      amyloidosis, due to nervous deposits of a genetic variant transthyretin produced
      by the liver and characterized by both sensorimotor and autonomic neuropathy.
      Left ventricular systolic dysfunction is rare, but conduction disturbances and
      sudden deaths can occur. The neurological status of the heart has not been
      elucidated, and an alteration of the sympathetic nerves may be involved. We
      studied 17 patients (42+/-12 years) before liver transplantation by iodine-123
      metaiodobenzylguanidine (MIBG) scintigraphy, heart rate variability analysis,
      coronary angiography, radionuclide ventriculography, rest thallium single-photon
      emission tomography (SPET) and echocardiography. Coronary arteries, left
      ventricular systolic function and rest thallium SPET were normal in all patients.
      Only mild evidence of amyloid infiltration was found at echocardiographic
      examination. Cardiac MIBG uptake was dramatically decreased in patients compared
      with age-matched control subjects (heart-to-mediastinum activity ratio at 4 h:
      1.36+/-0.26 versus 1.98+/-0.35, P<0.001), while there was no difference in MIBG
      washout rate. Heart rate variability analysis showed a considerable scatter of
      values, with high values in four patients despite cardiac sympathetic denervation
      as assessed by MIBG imaging. The clinical severity of the polyneuropathy
      correlated with MIBG uptake at 4 h but not with the heart rate variability
      indices. Cardiac MIBG uptake and the heart rate variability indices did not
      differ according to the presence or absence of conduction disturbances. Patients
      with FAP have sympathetic cardiac denervation as assessed by MIBG imaging despite
      a preserved left ventricular systolic function and cardiac perfusion, without
      correlation with conduction disturbances. Results of the heart rate variability
      analysis were more variable and this technique does not seem to be the best way
      to evaluate the extent of cardiac sympathetic denervation in FAP patients.

PMID- 10199950
TI  - Genetic susceptibility to radiation effects: possible implication for medical
      ionising radiation exposures.

PMID- 10199951
TI  - Heterochromatin.
AB  - The properties of heterochromatin are reconsidered in the context of our present
      understanding of gene silencing, telomeric and centromeric properties, position
      effect variegation and X-chromosome inactivation. It is proposed that the
      chromatin in heterochromatic chromosomal regions is generally similar in its
      molecular composition to that in silenced chromosomal regions. Heterochromatic
      appearance hence reflects not a particular quality of the respective chromosomal
      regions but only a specific kind of chromatin packaging comparable to that
      required for the inactivation of genes. This packaging may be initiated by
      particular signals in the DNA but can be propagated over more extended
      chromosomal regions by the formation of multiprotein complexes that interact with
      histones and possibly cell-specific additional components (RNA or proteins) that
      determine the status of the chromosome in a particular cell type.

PMID- 10199952
TI  - CHD1 interacts with SSRP1 and depends on both its chromodomain and its
      ATPase/helicase-like domain for proper association with chromatin.
AB  - CHD1, an Mr approximately 200,000 protein that contains a chromodomain (C), an
      ATPase/helicase-like domain (H) and a DNA-binding domain (D), was previously
      shown to be associated with decompacted interphase chromatin in mammalian cells
      and with transcriptionally active puffs and interbands in Drosophila polytene
      chromosomes. We now show by transient transfection experiments with genes
      expressing wild-type and mutant forms of CHD1 that both the C and H domains are
      essential for its proper association with chromatin. We also present evidence for
      an in vivo interaction between CHD1 and a novel HMG box-containing protein,
      SSRP1, which involves an amino-terminal segment of CHD1 that does not include the
      chromodomain. Immunocytochemical analyses indicated that CHD1 and SSRP1
      colocalize in both mammalian nuclei and Drosophila polytene chromosomes.

PMID- 10199953
TI  - Identification and characterization of mouse homologue to yeast Cdc7 protein and
      chromosomal localization of the cognate mouse gene Cdc7l.
AB  - The Cdc7 kinase is required for the G1/S-phase transition during the cell cycle
      and plays a direct role in the activation of individual origins of replication in
      Saccharomyces cerevisiae. Here, we report the identification of a mouse cDNA,
      MmCdc7, whose product is closely related in sequence to Saccharomyces cerevisiae
      Cdc7 as well as their human, Xenopus and Schizosaccharomyces pombe homologues.
      The MmCdc7p contains the conserved subdomains common to all protein
      serine/threonine kinases and three kinase inserts that are characteristic of
      members of the Cdc7 protein family. We have mapped the locus of the MmCdc7 gene
      to chromosome 5, band 5E. Conservation of structures among members of the Cdc7
      related proteins suggests that these proteins play a key role in the regulation
      of DNA replication during the cell cycle in all eukaryotes.

PMID- 10199954
TI  - Comparative mapping of cosmids and gene clones from a 1.6 Mb chromosomal region
      of Drosophila melanogaster in three species of the distantly related subgenus
      Drosophila.
AB  - The successful hybridization of cosmid clones from Drosophila melanogaster
      (Sophophora subgenus) to the salivary gland chromosomes of other species as
      distantly related as those in the Drosophila subgenus attests their great
      potential for unravelling genome evolution. We have carried out, using 28 cosmids
      and 13 gene clones, a study of the organization of the D. melanogaster 95A-96A
      chromosomal region in three Drosophila subgenus species: D. repleta, D. buzzattii
      and D. virilis. These clones were first used to built an accurate map of this 1.6
      Mb region of D. melanogaster chromosome 3R (Muller's element E). Then, they were
      hybridized and mapped to the homologous chromosome 2 of the other three distantly
      related species. The studied region is disseminated over 13 different sites of
      chromosome 2 in the Drosophila subgenus species, which implies a minimum of 12
      inversion breakpoints fixed between the two subgenera. Extrapolation to the
      entire chromosome gives 90 fixed inversions. The D. melanogaster Pp1-96A-Acr96Aa
      segment conserved in D. repleta and D. buzzatii is longer than previously thought
      and is also conserved in D. virilis. In addition, three other D. melanogaster
      segments conserved in the three Drosophila subgenus species were found. Finally,
      our data indicate significant statistical differences in the evolution rate of
      Muller's element E among lineages, a result that agrees well with the previous
      cytogenetic data.

PMID- 10199955
TI  - Detection of poly(ADP-ribose) synthesis in Drosophila testes upon gamma
      irradiation.
AB  - Poly(ADP-ribose) polymerase (PARP) activity is widespread among eukaryotes. Upon
      DNA damage PARP binds to DNA strand breaks and transfers ADP-ribose residues from
      NAD+ to acceptor proteins and to ADP-ribosyl protein adducts. This leads to
      branched polymers of protein-coupled poly(ADP-ribose) (pADPr). Because the
      germline of Drosophila has recently become important in the study of DNA double
      strand break repair (DSBR) as opposed to somatic DSBR we tested whether the
      catalytic activity of PARP can be stimulated by gamma-irradiation during
      Drosophila spermatogenesis. Using antibodies against pADPr we detected a
      significant increase in PARP activity in male germline cells during
      spermatogenesis upon gamma-irradiation. Different stages of spermatogenesis
      revealed different subnuclear localization patterns of pADPr. In premeiotic and
      postmeiotic cells pADPr localized in a pattern overlapping with lamin and
      topoisomerase II at the nuclear rim. In primary spermatocytes pADPr is associated
      with three loci corresponding to the chromosomes at the nuclear periphery.

PMID- 10199956
TI  - The extent and position of homoeologous recombination in a distant hybrid of
      Alstroemeria: a molecular cytogenetic assessment of first generation backcross
      progenies.
AB  - To estimate the extent and position of homoeologous recombination during meiosis
      in an interspecific hybrid between two distantly related Alstroemeria species,
      the chromosome constitution of six first generation backcross (BC1) plants was
      analysed using sequential fluorescent in situ hybridization (FISH) and genomic in
      situ hybridization (GISH) analysis. Four different probes were used for the FISH
      analysis: two species-specific and two rDNA probes. The six BC1 plants were
      obtained from crosses between the hybrid A. aurea x A. inodora with its parent A.
      inodora. GISH clearly identified all chromosomes of both parental genomes as well
      as recombinant chromosomes. The sequential GISH and FISH analysis enabled the
      accurate identification of all individual chromosomes in the BC1 plants,
      resulting in the construction of detailed karyotypes of the plants. The
      identification of the recombinant chromosomes provided evidence which chromosomes
      of the two species are homoeologous. Two of the BC1 plants were aneuploid
      (2n=2x+1=17) and four triploid (2n=3x=24), indicating that both n and 2n gametes
      were functional in the F1 hybrid. Using GISH, it was possible to estimate
      homeologous recombination in two different types of gametes in the F1 hyrid. The
      positions of the crossover points ranged from highly proximal to distal and the
      maximum number of crossover points per chromosome arm was three. Compared with
      the aneuploid plants, the triploid plants (which received 2n gametes) clearly
      possessed fewer crossovers per chromosome, indicating reduced chromosome
      pairing/recombination prior to the formation of the 2n gametes. Besides
      homeologous recombination, evidence was found for the presence of structural
      rearrangements (inversion and translocation) between the chromosomes of the
      parental species. The presence of the ancient translocation was confirmed through
      FISH analysis of mitotic and meiotic chromosomes.

PMID- 10199957
TI  - Demonstration of a DNase-sensitive network associated with the nuclear pore
      complexes in rat liver nuclei.
AB  - Rat liver nuclei have been studied by transmission electron microscopy after
      resuspension in a phosphate-buffered salt solution containing SO2-4 as the
      quantitatively dominant anion. Owing to the high solubility of chromatin in the
      presence of SO2-4 instead of Cl- at isotonicity, nuclei are depleted for
      chromatin by DNase I digestion in this buffer, eliminating the need for high-salt
      extraction. This shows that at least 75% of the nuclear pore complexes are
      associated with fibrogranular structures, which ramify as a network throughout
      the nucleus, interconnecting the nuclear lamina, interchromatin granule clusters
      and nucleoli. Perichromatin granules are located in this material proximal to the
      nuclear pore complexes. Most of the chromatin is removed without major impact on
      the network, but below a level of 25% residual chromatin there is a considerable
      reduction of this material, and only about 15% of the connections to the nuclear
      pore complexes are resistant to digestion with DNase I or streptodornase A and B.
      The percentage of nuclear pore complexes connected to the network is further
      reduced by salt extraction and RNase treatment. These results suggest that DNA is
      an integral part of the network, which presumably plays a role in nucleo
      cytoplasmic transport of RNA and protein.

PMID- 10199959
TI  - From classical mutations and concepts to molecular regulation and evolutionary
      models of development.

PMID- 10199960
TI  - Molecular control of vertebrate limb development, evolution and congenital
      malformations.
AB  - The vertebrate limb is a powerful model system for studying the cellular and
      molecular interactions that determine morphological pattern during embryonic
      development. Recent advances in our understanding of these interactions have shed
      new light on the molecular mechanisms of vertebrate limb development, evolution
      and congenital malformations. The transfer of information has, until recently,
      been largely one way, with developmental studies informing our understanding of
      the fossil record and clinical limb anomalies; however, evolutionary and clinical
      studies are now beginning to shed light onto one another and onto basic
      developmental processes. In this review, we discuss recent advances in these
      fields and how they are interacting to improve our understanding of vertebrate
      limb biology.

PMID- 10199961
TI  - Hox genes in digit development and evolution.
AB  - Homeobox genes located in the 5' part of the HoxA and HoxD complexes are required
      for proliferation of skeletal progenitor cells of the vertebrate limb. Specific
      combinations of gene products determine the length of the upper arm (genes
      belonging to groups 9 and 10), the lower arm (groups 10, 11 and 12) and the
      digits (groups 11, 12 and 13). In these different domains, individual gene
      products quantitatively contribute to an overall protein dose, with predominant
      roles for groups 11 and 13. Quantitative reduction in the gene dose in each set
      results in truncations of the corresponding anatomical regions. The physical
      order of the genes in the HoxA and HoxD complexes, as well as a unidirectional
      sequence in gene activation, allow for completion of the process in a precise
      order, which in turn makes possible the sequential outgrowth of the respective
      primordia. While the skeletal patterns of upper and lower limb are relatively
      stable throughout the tetrapods, more variation is seen in the digits. Molecular
      analysis of the underlying regulatory processes promises further exciting
      insights into the genetic control of development, pathology and the course of
      evolution.

PMID- 10199962
TI  - Do 5'Hoxd genes play a role in initiating or maintaining A-P polarizing signals
      in the limb?
AB  - The analysis of multiple null mutants generated through targeted disruption
      indicates that the 5' members of the Hoxd and Hoxa clusters determine the
      skeletal pattern in the limb by regulating the formation and growth of the
      different chondrogenic precursors for the skeletal elements. While these studies
      have established that together these genes are the major players in regulating
      formation of the limb skeleton, the roles of individual members have often been
      difficult to evaluate fully due to extensive functional overlap between various
      5'Hoxd and 5'Hoxa genes. The analysis of gain-of-function mutants provides a
      complementary approach to elucidate gene function in the presence of multiple
      redundancies. This approach has recently revealed that Hoxd-12 can induce Sonic
      hedgehog and suggests a new role for certain 5'Hoxd genes in the initiation of
      Sonic hedgehog expression and its maintenance through feedback regulation. Thus,
      some 5'Hoxd genes may be a part of the regulatory network that positions and
      reinforces polarizing signals in the posterior-distal limb bud.

PMID- 10199963
TI  - Fibroblast growth factor receptors (FGFRs) and their roles in limb development.
AB  - Fibroblast growth factor (FGF) receptors constitute a family of four membrane
      spanning tyrosine kinases (FGFR1-4) which serve as high-affinity receptors for 17
      growth factors (FGF1-17). To study functions of FGF/ FGFR signals in development,
      mice that carry mutations in each receptor have been created by gene targeting.
      Analysis of these mutant mice revealed essential functions of FGF receptors in
      multiple biological processes, including mesoderm induction and patterning, cell
      growth and migration, organ formation and bone growth. In this review we discuss
      recent work with FGF receptors to illustrate mechanisms, through which the
      FGF/FGFR signals specify vertebrate limb initiation, outgrowth and patterning.

PMID- 10199964
TI  - Fibroblast-growth-factor-induced additional limbs in the study of initiation of
      limb formation, limb identity, myogenesis, and innervation.
AB  - In this review, we focus on the additional limb induced by members of the
      fibroblast growth factor (FGF) family in the flank of chick embryos. The
      "additional limb" was first reported 73 years ago by Balinsky in 1925. He grafted
      otic vesicle to the flank of newt embryos and observed the formation of the
      "additional limb." In 1995, formation of an additional limb was found to be
      induced by FGF in the chick embryo. This finding subsequently led to the recent
      understanding of how the limb bud is initially formed, how the limb position is
      determined, and how the limb identity is determined. Thus, the additional limb
      has been recognized as a useful experimental system for the study of limb
      development and its relation to the regionalization of the body. Furthermore,
      since limb muscles are formed from cells which have migrated from somites and
      innervation to them takes place from the spinal cord, the additional limb would
      also be a powerful tool with which to study the relation of limb morphogenesis to
      developmental processes of the spinal cord and somites. This review consists of
      five sections: (1) "Introduction," (2) "How to make additional limbs," (3)
      "Characteristics of the additional limb," (4) "Studies with the additional limb,"
      and (5) "Concluding remarks." In the second section, techniques to make
      additional limbs are reviewed, showing that additional limbs can be made by
      fairly easy manipulation of the chick embryo. In the third section, the
      characteristics analyzed so far of the additional limb are summarized, focusing
      on its morphology. In the fourth section, recent studies on the use of the
      additional limb are reviewed: experiments on the additional limb have been
      performed to elucidate the mechanisms governing determination of limb identity by
      Hox codes and the Tbx family and initiation of limb formation by FGF10. In
      addition, the roles of SF/HGF in the formation of limb muscles have also been
      investigated using the additional limb. In the near future, the additional limb
      will be also used in the study of innervation from the spinal cord, and probably
      migration of neural crest cells.

PMID- 10199965
TI  - T-box genes and the formation of vertebrate forelimb- and hindlimb specific
      pattern.
AB  - Limb patterning is thought to be a multistep process involving specification of
      the limb fields, establishment of defined signaling centers that globally inform
      cells of their position, interpretation of positional signals, and regulated
      growth and differentiation of the limb structures. Great progress has been made
      over the past few years in identifying the molecular players that control limb
      outgrowth and patterning, in particular, how the limb axes are specified.
      However, the molecular mechanism for determination of the morphological and
      functional differences between forelimbs and hindlimbs has remained elusive. The
      recent identification of a series of limb-specific transcription factors has now
      provided excellent candidates for such upstream regulators of limb identity, and
      has allowed new insights into the regulatory network of making a hand or a foot.

PMID- 10199966
TI  - Dorsoventral patterning of the vertebrate limb: a process governed by multiple
      events.
AB  - In this review, we detail recent studies which have led to the first molecular
      insights into dorsoventral vertebrate limb patterning. In keeping with classical
      experiments which defined ectodermal-mesodermal signaling as an important
      component of limb bud dorsoventral axis specification, the genes identified to
      date to be critically important for proper dorsoventral limb patterning include
      both ectodermally and mesodermally expressed cell:cell signaling molecules and
      transcription factors. A surprising complexity to dorsoventral vertebrate limb
      patterning has been revealed by gene targeting in the mouse and lineage tracing
      in the chick, with current models suggesting that the dorsoventral limb axis is
      specified by distinct mechanisms in the proximal versus distal limb.

PMID- 10199967
TI  - Gli genes and limb development.
AB  - During development of the limb Shh plays a key role as a mediator of zone of
      polarizing activity (ZPA). However, the molecular mechanisms by which Shh directs
      anterior/posterior patterning in the limb remain unknown. Members of the Gli gene
      family encode zinc-finger transcription factors and represent likely candidates
      for being regulators of Shh target genes. In this review we would like to
      summarize the current knowledge on expression and function of Gli genes in limb
      development.

PMID- 10199968
TI  - Formin defines a large family of morphoregulatory genes and functions in
      establishment of the polarising region.
AB  - Formin was originally isolated as the gene affected by the murine limb deformity
      (ld) mutations, which disrupt the epithelial-mesenchymal interactions regulating
      patterning of the vertebrate limb autopod. More recently, a rapidly growing
      number of genes with similarity to formin have been isolated from many different
      species including fungi and plants. Genetic and biochemical analysis shows that
      formin family members function in cellular processes regulating either
      cytokinesis and/or cell polarisation. Another common feature among formin family
      members is their requirement in morphogenetic processes such as budding and
      conjugation of yeast, establishment of Drosophila oocyte polarity and vertebrate
      limb pattern formation. Vertebrate formins are predominantly nuclear proteins
      which control polarising activity in limb buds through establishment of the
      SHH/FGF-4 feedback loop. Formin acts in the limb bud mesenchyme to induce apical
      ectodermal ridge (AER) differentiation and FGF-4 expression in the posterior AER
      compartment. Finally, disruption of the epithelial-mesenchymal interactions
      controlling induction of metanephric kidneys in ld mutant embryos indicates that
      formin might function more generally in transduction of morphogenetic signals
      during embryonic pattern formation.

PMID- 10199969
TI  - Regulation by members of the transforming growth factor beta superfamily of the
      digital and interdigital fates of the autopodial limb mesoderm.
AB  - Embryonic limb outgrowth is accomplished by the proliferation of mesodermal cells
      in the progress zone. In this region, mesodermal cells are maintained in an
      undifferentiated and proliferating state by the action of the apical ectodermal
      ridge (AER). Differentiation of these cells into individual skeletal elements
      occurs when the cells are displaced proximally and leave the influence of the AER
      as a consequence of the accumulation of cells in that region. Here we review the
      evidence obtained in the last few years showing that members of the transforming
      growth factor beta (TGFbeta) subfamily and bone morphogenetic proteins (BMPs) act
      as proximal signals in the autopod regulating the fate of the progress zone cells
      towards chondrogenesis or apoptosis. Our findings show that apoptosis is
      regulated by BMPs while chondrogenesis requires the interaction of TGFbetas and
      BMPs. Fibroblast growth factors (FGFs) produced by the AER exert an opposite
      function to both TGFbetas and BMPs, maintaining the progress zone cells in an
      undifferentiated state.

PMID- 10199970
TI  - From head to toe: conservation of molecular signals regulating limb and
      craniofacial morphogenesis.
AB  - Recent evidence indicates that many molecules involved in generating and
      patterning the limbs also play a role during craniofacial morphogenesis. On the
      surface, this is an unexpected finding given that these regions of the body have
      separate evolutionary origins, are composed of different embryonic tissues, and
      are quite dissimilar in their anatomy. Results from several experiments involving
      Sonic hedgehog and retinoic acid point to a remarkable conservation of the
      signaling pathways mediated by these morphogens across multiple organ systems.
      Moreover, mutants such as the extra-toes and doublefoot mouse, and the talpid
      chicken also provide insights on common developmental processes that underlie the
      formation of the limbs and face. The identification of highly conserved aspects
      of morphogenesis is important for understanding fundamental mechanisms of
      development, as well as for revealing the common denominator of countless birth
      defects and providing new strategies for their prevention and cure.

PMID- 10199971
TI  - BMP/GDF-signalling interactions during synovial joint development.
AB  - The synovial joint arises from an initial condensation of cells that subsequently
      develops into distinct skeletal structures, separated by the joint. Bone
      morphogenetic proteins (BMPs) and growth and differentiation factors (GDFs) have
      a fundamental role during skeletogenesis, including joint formation. Development
      of the joint appears to be dependent on the differential expression/activity of
      the related BMP and GDF subfamilies. Gdf-5 is expressed in the developing joints
      and is necessary for the formation of some joints. In contrast, recent data has
      shown that antagonism of the BMP family is crucial for joint formation. Here, we
      review mechanisms of how BMP signalling may be antagonised/modified. We also
      describe the expression of Bmp-2 and Bmp-4 together with two BMP antagonists,
      chordin and noggin, during chick joint development. Finally, we discuss possible
      mechanisms of how a joint forms and the evidence that the joint is a 'signalling
      centre' that may coordinate the development of adjacent skeletal structures.

PMID- 10199972
TI  - The recombinant limb as a model for the study of limb patterning, and its
      application to muscle development.
AB  - The recombinant limb is a model system that has proved fruitful for analyzing
      epithelial-mesenchymal interactions and understanding the functional properties
      of the components of the limb bud. Here we present an overview of some of the
      insights obtained through the use of this technique. Among these are the
      understanding that fore or hind limb identity is inherent to the limb bud
      mesoderm, that the apical ectodermal ridge (AER) is a permissive signaling center
      and that the limb bud ectoderm plays a central role in the control of
      dorsoventral polarity. Recombinant limb studies have also allowed the
      identification of the affected tissue component in several limb mutants. More
      recently this model has been applied to the study of regulation of gene
      expressions related to patterning. In this report we use recombinant limbs to
      analyze pattering of the Pax3 expressing limb muscle cell lineage in the early
      stages of limb development. In recombinant limbs made without the zone of
      polarizing activity (ZPA), myoblasts appear intermingled with other mesodermal
      cells at the beginning of the recombinant limb development. Rapidly thereafter,
      the muscle precursors segregate and organize around the central forming
      chondrogenic core of the recombinant. Although this segregation is reminiscent of
      that occurring during normal development, the myoblasts in the recombinant fail
      to proliferate appropriately and also fail to migrate distally. Consequently, the
      muscle pattern in the recombinant limb is defective indicating that normal
      patterning cues are absent. However, recombinant limbs polarized with a ZPA
      exhibited a larger mass of muscle cells and a more normal morphogenesis,
      supporting a role for this signaling center in limb muscle development. Finally,
      we have ruled out host somite contributions to recombinant limbs by grafting
      chick recombinant limbs to quail hosts. This initial report demonstrates the
      value of the recombinant limb model system for dissecting the environmental cues
      required for normal muscle limb patterning.

PMID- 10199973
TI  - Muscle development during vertebrate limb outgrowth.
AB  - Limb development has become one of the model systems for studying vertebrate
      development. One crucial aspect in limb development is the origin,
      differentiation and patterning of muscle. Much progress has been made in recent
      years towards understanding this process. One of the general observations is that
      the genes involved in limb muscle development appear to be very similar to those
      involved in muscle development in other regions of the embryo. In this review, we
      summarize some of the genes and mechanisms that regulate limb muscle development
      and discuss various avenues along which a deeper understanding can be gained of
      how muscle cells originate and differentiate in different tissues during
      vertebrate development.

PMID- 10199974
TI  - Extrinsic influences on limb muscle organisation.
AB  - Skeletal muscle within the vertebrate limb originates from the somite. Much work
      has focussed upon the role of secreted signalling molecules of the Hedgehog,
      fibroblast growth factor (FGF), bone morphogenetic protein (BMP), and Wnt
      families plus their associated antagonists in establishing somitic cell types,
      yet there is no consensus on how these signals combine to influence muscle
      patterning. When somitic cells migrate into the limb bud, they become subject to
      a new set of guidance and patterning cues. Here we discuss the possible roles
      played by signalling proteins, particularly Hedgehogs, in guiding the cells of
      the limb musculature to their fate.

PMID- 10199975
TI  - Determination and development of the larval muscle pattern in Drosophila
      melanogaster.
AB  - This review describes briefly what is known about the early steps of mesoderm
      differentiation in the fruitfly Drosophila melanogaster. After a summary of
      general aspects including mesoderm differentiation, mesoderm cell migration and
      subdivision of the mesoderm, more detail is given about the specification of
      muscle progenitor cells, due to their role as the earliest obvious landmarks in
      muscle fiber development in Drosophila. Particular focus is given to recent
      results on the role of asymmetric cell division in muscle differentiation.
      Furthermore a short summary of myoblast fusion is provided.

PMID- 10199976
TI  - Myotome formation: a multistage process.
AB  - The epaxial muscles of the body are localized in a dorsomedial position with
      respect to the axial structures, attach to the vertebral column and are concerned
      with maintenance of posture and movements of the vertebral column. The epaxial
      musculature derives from the myotome, a transient embryonic structure whose
      formation is initiated at the epithelial somite stage and is accomplished
      following complete dissociation of the epithelial dermomyotome. Recent results
      suggest that myotome development is a multistage process, characterized by
      addition of sequential waves of muscle progenitors. A first wave originates along
      the medial part of the epithelial somite and gives rise to a primary myotomal
      structure; a second wave arises from the rostral and caudal lips of the
      epithelial dermomyotome and from the dorsomedial lip, which contributes
      indirectly through the rostral and caudal edges, and a third wave which is
      composed of mitotically active resident progenitors accounts for significant
      growth of the myotomal mass and for its transition into epaxial muscle. In this
      review we discuss the origin, migration and known cellular and molecular features
      that characterize each wave of progenitors that colonize the myotome.

PMID- 10199977
TI  - Regulation of hypaxial muscle development.
AB  - The majority of skeletal muscles in higher vertebrates are hypaxial and stem from
      the lateral lip of the dermomyotomes. Various external signals converge on the
      dorsolateral quadrant of the somite to specify the hypaxial muscle precursors, to
      discriminate between migratory and non-migratory cells and to allow delamination
      of precursors destined for long-range migration. Within the somite, Pax3 acts as
      upstream regulator of hypaxial muscle development. Downstream targets are cMet
      and Lbx1, which may independently control identity, differentiation and motility
      of migratory muscle precursors.

PMID- 10199978
TI  - The alpha7beta1 integrin in muscle development and disease.
AB  - The alpha7beta1 integrin is a laminin receptor on the surface of skeletal
      myoblasts and myofibers. Alternative forms of both the alpha7 and beta1 chains
      are expressed in a developmentally regulated fashion during myogenesis. These
      different alpha7beta1 isoforms localize at specific sites on myofibers and appear
      to have distinct functions in skeletal muscle. These functions include the
      migration and proliferation of developing myoblasts, the formation and integrity
      of neuromuscular and myotendinous junctions, and the "gluing" together of muscle
      fibers that is essential to the generation of contractile force. The alpha7beta1
      integrin appears to be both directly and indirectly causally related to several
      muscle diseases. Enhanced expression of alpha7beta1-mediated linkage of the
      extracellular matrix is seen in Duchenne muscular dystrophy and may compensate
      for the absence of the dystrophin-mediated linkage. Downregulation of expression
      of the integrin may contribute to the development of pathology in congenital
      laminin deficiencies. Mutations in the alpha7 integrin gene underlie additional
      congenital muscle diseases. The functional roles of this integrin in the
      formation and stability of the neuromuscular and myotendinous junctions and its
      localization between fibers suggest that altered expression or function of this
      integrin may have widespread involvement in other myopathies. The localization of
      the alpha7 gene at human chromosome 12q13 is a useful clue for focusing such
      studies.

PMID- 10199979
TI  - M-cadherin and its sisters in development of striated muscle.
AB  - Cadherins are calcium-dependent, transmembrane intercellular adhesion proteins
      with morphoregulatory functions in the development and maintenance of tissues. In
      the development of striated muscle, the expression and function of mainly M-, N-,
      and R-cadherin has been studied so far. While these three cadherins are expressed
      in skeletal muscle cells, of these only N-cadherin is expressed in cardiac
      muscle. In this review, M-, N-, and R-cadherin are discussed as important players
      in the terminal differentiation and possibly also in the commitment of skeletal
      muscle cells. Furthermore, reports are described which evaluate the essential
      role of N-cadherin in the formation of heart tissue.

PMID- 10199980
TI  - Genetic and epigenetic control of muscle development in vertebrates.
AB  - The skeletal body muscle of vertebrates is derived from segmentally arranged
      mesodermal structures, the somites. Only the dorsal epithelial half of the
      somite, the dermomyotome, gives rise to muscle cells during normal development.
      Head muscle takes its origin from the somites, the unsegmented paraxial head
      mesoderm and the prechordal mesoderm. Some muscle precursor cells, for instance
      those for limb and tongue muscle, migrate over considerable distances before
      differentiating at their target sites. In recent years, our understanding of the
      molecular events underlying myogenesis has increased considerably. Muscle
      differentiation is preceded by several steps during which precursor cells are
      specified. Markers of myogenic specification are myf5, myoD, mrf4 and myogenin,
      which encode transcription factors of the basic helix-loop-helix family. These
      factors bind to promoters of many muscle-specific genes and interact with MEF2
      (myocyte enhancer binding factor-2) belonging to the MADS (MCM1, agamous,
      deficiens, serum response factor) box transcription factors. Signalling events
      leading to myogenic precursor cell specification and to the formation of muscle
      fibres are being elucidated. Inductive signals emanate from the neural tube,
      notochord and ectoderm. Controversial findings concerning the role of the
      notochord and neural tube in muscle development suggest that the epigenetic
      events leading to myogenesis are more complex than originally anticipated.
      Signals from the lateral plate counteract those from the axial organs and induce
      the locally restricted emigration of muscle precursor cells. Future
      investigations will have to show how signalling molecules and their receptors
      interact in the process of fine-tuning muscle formation in the embryo.

PMID- 10199982
TI  - The renewal of orthopedic surgery toward the twenty-first century.

PMID- 10199983
TI  - Factors affecting the rectus femoris-patellar tendon Q-angle, measured using a
      computed tomographic scan.
AB  - We devised a method to measure the Q-angle (the angle between the rectus femoris
      and the patellar ligament), using computed tomography (CT), in 1993. In this
      study, I investigated the lateral shift at each point forming the angle as
      factors affecting the Q-angle. The study group consisted of 83 patients with
      recurrent patellar dislocation (83 lower limbs) and a control group of 55 healthy
      people (55 lower limbs). A lateral shift was found in the anterosuperior iliac
      spine (ASIS) in the dislocation group compared with the control group (P < 0.01).
      A lateral shift was also found in the anteroinferior iliac spine (AIIS) in the
      dislocation group compared with the control group (P < 0.05). A medial shift was
      found in the bottom of the groove of the femoral condyle in the dislocation group
      compared with the control group (P < 0.001). A lateral shift was also seen in the
      tibial tubercle of the dislocation group in comparison with the control group (P
      < 0.0001). Lateral shift of the tibial tubercle may be the main factor
      influencing the Q-angle, as measured by CT.

PMID- 10199981
TI  - Transcriptional mechanisms regulating MyoD expression in the mouse.
AB  - The basic-loop-helix transcription factors, MyoD and Myf-5, are essential
      regulators of skeletal muscle lineage determination in vertebrates.
      Investigations into the signaling and response systems regulating MyoD and Myf-5
      gene expression in muscle progenitor cells have led to the identification of
      molecular signals and DNA regulatory regions that control expression of these
      muscle regulatory genes. Here we discuss recent advances in these areas, with
      emphasis on in vivo analyses of MyoD transcription.

PMID- 10199984
TI  - New method for measuring area of spinal canal after double-door laminoplasty.
AB  - In the double-door laminoplasty procedure used for patients with cervical
      myelopathy, techniques to obtain a wider spinal canal have been tested. We
      hypothesized that making the lateral gutters as lateral as possible may be
      effective for obtaining a wider spinal canal. In this study we aimed to test our
      hypothesis by using a new measurement method to assess the postoperative cross
      sectional area of the spinal canal. Fifty-six vertebrae were operated on in 11
      patients, using the STSS spacer (Asahi Optical, Tokyo, Japan). On computed
      tomography (CT) scans, the most posterior edge of a space-occupying lesion was
      defined as point A and a horizontal line through point A was drawn parallel to
      the posterior wall of the vertebral body (line X). Two oblique lines were drawn
      along the medial margin of the bilateral split laminae (lines R and L). The
      triangular area enclosed by lines X, R, and L was defined as the substantial area
      of the spinal canal (SASC). A horizontal line through the median points of the
      bilateral facet joint in the anteroposterior direction was defined as line B.
      According to the relative position of line X to line B, two types of vertebra
      were observed: In type 1, line X was located ventral to line B; in type 2, line X
      was located dorsal to line B. The mean data values for type 1 vertebra were:
      SASC, 133.1 mm2; ATD, 22.9 mm; angle R, 61.3 degrees; and angle L, 61.8 degrees.
      The mean data values for type 2 vertebra were: SASC, 99.8 mm2; ATD, 20.1 mm;
      angle R, 58.6 degrees; and angle L, 57.5 degrees. There were significant
      differences between types 1 and 2 vertebrae in values both for SASC and ATD (P <
      0.01). There were no significant differences between types 1 and 2 vertebrae
      regarding angles R and L. The difference in SASC in the two types appeared to
      arise from the difference in ATD. In other words, the degree of enlargement of
      the spinal canal was determined not by the inclination of the bilateral split
      laminae, but by the transverse diameter. This result supports the validity of our
      hypothesis. In a double-door laminoplasty, to obtain a wider spinal canal, the
      lateral gutters must be made as lateral as possible (i.e., at the medial border
      of the facet joints, especially in type 2 vertebra). On the preoperative CT scan,
      the relative positions of the large-volume lesion and the facet joint must be
      noted.

PMID- 10199985
TI  - Clinical outcome of revision of the patellar component in total knee
      arthroplasty. A 2- to 7-year follow-up study.
AB  - The objectives of this study were to determine the relationship between the
      thickness of the residual patellar bone and the composite patella-patellar
      component, and the clinical outcome in patients who had undergone revision total
      knee arthroplasty (TKA) with a biconvex patellar component. Clinical outcome
      after at least a 2-year follow-up was determined using the Knee Society pain and
      functional scores, and radiographically, with the thicknesses of the patellar
      bone and composite measured in 23 knees (22 patients). The thickness of the
      patellar bone after preparation for a biconvex patellar component was
      significantly less for revised patellae (average, 5.0 mm) than the primary
      patellae (average, 7.9 mm; P < 0. 01). Differences in thickness between
      preoperative patellae, primary composites, and revision composites did not
      significantly affect postoperative results. There were no patellar fractures,
      despite the relatively thin bone remnant in the revision patients. Radiolucency
      was observed in 8% of the revisions. A patella with a thickness of residual bone
      of as little as 5 mm can provide favorable clinical results in revision TKA with
      restoration of the composite thickness of the patella achieved using a thick but
      small-diameter biconvex patellar component.

PMID- 10199986
TI  - Gait analysis following varus osteotomy of the femur for hip osteoarthritis.
AB  - The purpose of this study was to evaluate differences in the gait patterns of
      healthy and osteoarthritic hips, and changes in these patterns after
      intertrochanteric varus osteotomy of the femur, in relation to the strength of
      the muscles around the hip joint. We measured the strength ratio of hip abductor
      muscles, temporal and distance factors, and pelvic movement, and carried out
      dynamic electromyography (EMG) in 24 women who underwent unilateral varus
      osteotomy of the femur for hip osteoarthritis (OA), 30 non-surgically-treated
      women with hip OA, and 54 healthy women. The stance phase time was shorter and
      the strength ratio of hip abductor muscles was lower in the operated patients
      than these values in the other two groups, changes in pelvic obliquity and tilt
      were smaller, and changes in the percent maximum voluntary contraction of the
      gluteus medius and tensor fascia latae muscles were greater than these values in
      the healthy subjects. This study showed the postoperative reappearance of the
      simulated conditions in the hip before varus osteotomy of the femur, providing
      evidence that the pelvis was horizontally maintained during walking due to the
      decreased stance phase time and increased performance of the hip abductor muscles
      achieved after this procedure.

PMID- 10199987
TI  - Quantitative evaluation of gait pattern in patients with osteoarthrosis of the
      knee before and after total knee arthroplasty. Gait analysis using a pressure
      measuring system.
AB  - Using a pressure measuring system, we quantitatively evaluated gait pattern in
      patients with osteoarthrosis (OA) of the knee before and after total knee
      arthroplasty (TKA). In the OA group, the stance time was longer, and the average
      vertical component of the floor reaction force (AVF) was lower than the values in
      normal age-matched subjects. These gait parameters correlated with the clinical
      score. These results suggest that changes in the gait parameters reflect gait
      patterns that reduce load on the knee. The center of pressure (COP) under the
      foot was correlated with the axial alignment of the lower limb in the mid-stance
      phase. In the TKA group, the clinical scores and gait parameters were improved 12
      months after surgery compared with the preoperative values. The COP in the mid
      stance phase moved inward after the TKA. However, in patients examined more than
      2 years after a TKA, stance time and AVF did not reach normal levels, despite the
      patients' good clinical scores. These findings indicate that the gait pattern
      before surgery continues although pain on walking is reduced early after a TKA.
      Gait evaluation with a simple pressure measuring system revealed the changes in
      gait that are difficult to define by subjective clinical assessment.

PMID- 10199988
TI  - Intra-focal fixation for treating distal radius fracture: results of 104 cases.
AB  - Intra-focal fixation for a displaced distal radius fracture is a surgical option
      that achieves early functional recovery. We report a retrospective evaluation of
      the results with various types of distal radius fracture, using various fixation
      materials in 104 patients (69 women and 35 men; average age, 51.4 years; range, 4
      91 years). Fracture types classified according to Frykman were: 14 type I, 15
      type II, 6 type III, 16 type IV, 10 type V, 16 type VI, 9 type VII, and 18 type
      VIII. Fixation materials used were: conventional Kirschner wire in 6 patients,
      threaded Kirschner wire in 38, arum pins in 38, and conehead wedging screws in
      22. The results for patients with Frykman types V-VIII fractures were not as good
      as those for patients with types I-IV. The arum pin and conehead wedging screw
      were each superior to either Kirschner wire or threaded Kirschner wire in
      reducing the fracture and in maintaining fixation. Our evaluation suggested that
      intra-focal fixation was also suitable for treatment of an intra-articular
      fracture. In elderly patients, we recommend the arum pin and conehead wedging
      screw as fixation materials, and suggest short-term postoperative immobilization.

PMID- 10199989
TI  - A biomechanical study of posterolateral lumbar fusion using a three-dimensional
      nonlinear finite element method.
AB  - Biomechanical analyses under compressive load, flexion, and extension torque were
      performed, using a nonlinear three-dimensional finite element method, to evaluate
      stability in posterolateral fusion. Effects of facet fusion and disc denucleation
      on posterolateral fusion were also examined. Using an initially prepared L4-5
      motion segment model, we prepared a denucleation model, posterolateral fusion
      models classified by presence or absence of denucleation and facet fusion, and an
      interbody fusion model. In the denucleation model, rigidity was less than in the
      normal model, and maximum rigidity was analyzed for the interbody fusion model.
      The effect of denucleation on posterolateral fusion was also analyzed. Taking
      into account the instability of the anterior elements, including the
      intervertebral disc, appears to be clinically important. In the posterolateral
      fusion model under compressive load, the axis of rotation moved principally
      toward the fusion mass, and axial displacement and flexion rotation were induced.
      Sagittal rotation angles under flexion and extension torque were 1.5 degrees -2.3
      degrees at a maximum moment of 15 N-m, demonstrating elasticity of posterolateral
      fusion. When combined with facet fusion, posterolateral fusion yielded increase
      of load transfer across the lamina and decrease of rotation angle of about 10%
      under flexion-extension torque. Adjunctive clinical use of facet fusion should
      permit more solid posterolateral fusion.

PMID- 10199990
TI  - Effects of hyaluronan on periosteal grafts for large full-thickness defects in
      rabbit articular cartilage.
AB  - We studied the effects of hyaluronan (HA) on chondrogenesis in periosteal grafts
      in rabbit knees to elucidate the effects of this agent in the repair of articular
      cartilage. Large full-thickness defects of the articular cartilage were created
      in the anteromedial part of the femoral articular surface of bilateral knee
      joints. Periosteal grafts were then harvested and sutured onto the defects. HA
      was injected in the right knee immediately after the operation and then once a
      week for 4 weeks (HA group). The same volume of saline was injected in the left
      knee in the control group. The animals were killed 2, 5, 8, and 12 weeks after
      the operation. Macroscopic and histological findings of the regenerated tissue
      were evaluated with a semiquantitative histological grading system. The total
      histological scores of the HA group were better than those in the control group
      at each time examination point. At 12 weeks, in particular, the scores for
      surface regularity and integration to adjacent articular cartilage were
      significantly better in the HA group than in the control group (P < 0.05). No
      significant differences were observed between the two groups in regard to the
      area healed (%). HA may have beneficial effects on the repair of large full
      thickness defects of the articular cartilage with autologous periosteal grafts.

PMID- 10199991
TI  - Meniscus transplantation using a cryopreserved allograft. Histological and
      ultrastructural study of the transplanted meniscus.
AB  - We performed allogenic meniscus transplantation in rabbits and investigated the
      regenerative process in the transplanted meniscus with particular respect to its
      ultra-structure. Under a transmission electron microscope, the chondrocytes and
      extracellular matrix were degenerated or destroyed in week 0. Fibroblasts were
      observed 4-8 weeks postoperatively. Immature chondrocytes emerged at 12
      postoperative weeks. At 16 weeks, the newly formed chondrocytes and extracellular
      matrix were virtually normal. Although the diameter of collagen fibrils still
      varied, their arrangement was dense and the filaments had almost normal banding.
      This study demonstrated that newly formed chondrocytes may differentiate from
      fibroblasts 8-12 weeks after transplantation. The fibroblasts synthesized
      collagen fiber and glycosaminoglycan, indicating that repair of the extracellular
      matrix may be initiated 4-8 weeks postoperatively, becoming were active after 12
      weeks when the newly formed chondrocytes emerge. The extracellular matrix is
      injured during rapid freezing, cryopreservation, and slow thawing, and repair is
      delayed due to this deterioration. The extracellular matrix thus needs to be
      protected from injury as far as possible in order to promote its repair, since it
      normalizes more slowly than chondrocytes.

PMID- 10199992
TI  - External fixation in the distal forearm: its use in fractures and malunions.

PMID- 10199993
TI  - Production scheduling and rescheduling with genetic algorithms.
AB  - A general model for job shop scheduling is described which applies to static,
      dynamic and non-deterministic production environments. Next, a Genetic Algorithm
      is presented which solves the job shop scheduling problem. This algorithm is
      tested in a dynamic environment under different workload situations. Thereby, a
      highly efficient decoding procedure is proposed which strongly improves the
      quality of schedules. Finally, this technique is tested for scheduling and
      rescheduling in a non-deterministic environment. It is shown by experiment that
      conventional methods of production control are clearly outperformed at reasonable
      run-time costs.

PMID- 10199994
TI  - Evolutionary algorithms, homomorphous mappings, and constrained parameter
      optimization.
AB  - During the last five years, several methods have been proposed for handling
      nonlinear constraints using evolutionary algorithms (EAs) for numerical
      optimization problems. Recent survey papers classify these methods into four
      categories: preservation of feasibility, penalty functions, searching for
      feasibility, and other hybrids. In this paper we investigate a new approach for
      solving constrained numerical optimization problems which incorporates a
      homomorphous mapping between n-dimensional cube and a feasible search space. This
      approach constitutes an example of the fifth decoder-based category of constraint
      handling techniques. We demonstrate the power of this new approach on several
      test cases and discuss its further potential.

PMID- 10199995
TI  - FOX-GA: a genetic algorithm for generating and analyzing battlefield courses of
      action.
AB  - This paper describes FOX-GA, a genetic algorithm (GA) that generates and
      evaluates plans in the complex domain of military maneuver planning. FOX-GA's
      contributions are to demonstrate an effective application of GA technology to a
      complex real world planning problem, and to provide an understanding of the
      properties needed in a GA solution to meet the challenges of decision support in
      complex domains. Previous obstacles to applying GA technology to maneuver
      planning include the lack of efficient algorithms for determining the fitness of
      plans. Detailed simulations would ideally be used to evaluate these plans, but
      most such simulations typically require several hours to assess a single plan.
      Since a GA needs to quickly generate and evaluate thousands of plans, these
      methods are too slow. To solve this problem we developed an efficient evaluator
      (wargamer) that uses course-grained representations of this problem domain to
      allow appropriate yet intelligent trade-offs between computational efficiency and
      accuracy. An additional challenge was that users needed a diverse set of
      significantly different plan options from which to choose. Typical GA's tend to
      develop a group of "best" solutions that may be very similar (or identical) to
      each other. This may not provide users with sufficient choice. We addressed this
      problem by adding a niching strategy to the selection mechanism to insure
      diversity in the solution set, providing users with a more satisfactory range of
      choices. FOX-GA's impact will be in providing decision support to time
      constrained and cognitively overloaded battlestaff to help them rapidly explore
      options, create plans, and better cope with the information demands of modern
      warfare.

PMID- 10199996
TI  - Predicting epistasis from mathematical models.
AB  - Classically, epistasis is either computed exactly by Walsh coefficients or
      estimated by sampling. Exact computation is usually of theoretical interest since
      the computation typically grows exponentially with the number of bits in the
      domain. Given an evaluation function, epistasis also can be estimated by
      sampling. However this approach gives us little insight into the origin of the
      epistasis and is prone to sampling error. This paper presents theorems
      establishing the bounds of epistasis for problems that can be stated as
      mathematical expressions. This leads to substantial computational savings for
      bounding the difficulty of a problem. Furthermore, working with these theorems in
      a mathematical context, one can gain insight into the mathematical origins of
      epistasis and how a problem's epistasis might be reduced. We present several new
      measures for epistasis and give empirical evidence and examples to demonstrate
      the application of the theorems. In particular, we show that some functions
      display "parity" such that by picking a well-defined representation, all Walsh
      coefficients of either odd or even index become zero, thereby reducing the
      nonlinearity of the function.

PMID- 10199997
TI  - An evolutionary algorithm for interval solid transportation problems.
AB  - The Solid Transportation Problem arises when bounds are given on three item
      properties. Usually, these properties are source, destination and mode of
      transport (conveyance), and may be given in an interval way. This paper deals
      with solid transportation problems in which the data in the constraint set are
      expressed in an interval form, i.e. when sources, destinations and conveyances
      have interval values instead of point values. An arbitrary linear or nonlinear
      objective function is also considered. To solve the problem, an Evolutionary
      Algorithm which extends and generalizes other approaches considering only point
      values, is proposed.

PMID- 10199998
TI  - The natural history of asthma in adults: the problem of irreversibility.
AB  - Asthma is common, affecting 5% to 10% of adults; asthma is progressive, leading
      to irreversible obstruction in 80% of elderly patients; and asthma is complex,
      often complicated by coexisting lung diseases. This loss of lung function results
      from 4 independent pathologic conditions: (1) airway remodeling, especially in
      the small airways, from the lymphocytic-eosinophilic inflammation that
      characterizes asthma; (2) bronchiectasis; (3) postinfectious pulmonary fibrosis;
      and (4) emphysema and chronic bronchitis from tobacco smoke. Deterioration in
      lung function develops faster in nonallergic patients with intrinsic asthma
      during the period shortly after onset of asthma and in older patients. About 4%
      of patients die of asthma, and most are elderly. Death most often results from
      complications of irreversible obstruction or cardiotoxicity of bronchodilator
      therapy. More research is needed to improve therapy for preventing remodeling of
      small airways, to confirm the frequency of bronchiectasis and postinfectious
      fibrosis and to determine their causes, and to develop diagnostic criteria to
      identify these complications. Meanwhile, clinicians treating adult asthmatic
      patients need to be aggressive in preventing the damage from cigarette smoke; in
      immunizing for influenza and pneumococcus infection and identifying and treating
      respiratory infections, particularly at times of acute exacerbations; in
      diagnosing and managing bronchiectasis; and in objectively confirming the
      efficacy of asthma therapy to prevent illness from overtreatment with
      glucocorticoids and bronchodilators.

PMID- 10199999
TI  - Apoptosis: mechanisms of life and death in the immune system.
AB  - When normal cells die, it is almost always by the process of apoptosis, which is
      a morphologic description. Some cells die readily and are rapidly replaced;
      others live as long as we do. Because apoptotic morphology is similar from cell
      to cell, researchers have embarked on an intense search for a common underlying
      biochemical process. There is an apoptotic mechanism or cell death program, which
      is expressed in embryos and throughout life. Most tissues, and especially the
      skin, gut, and immune system, depend on well-ordered apoptosis and cell
      replacement. Apoptosis can fail to occur, as in the newly described autoimmune
      lymphoproliferative syndrome, or be turned on pathologically, as in degenerative
      diseases. We would like to induce apoptosis in dangerous cells or block it to
      preserve valuable cells. We need to know more about how apoptosis is regulated
      and what we can do to influence the process.

PMID- 10200000
TI  - "Their's but to do and die": eosinophil longevity in asthma.

PMID- 10200001
TI  - Prevalence of peanut and tree nut allergy in the US determined by a random digit
      dial telephone survey.
AB  - BACKGROUND: Allergy to peanuts and tree nuts (TNs) is one of the leading causes
      of fatal and near-fatal food-induced allergic reactions. These allergies can be
      lifelong and appear to be increasing in prevalence. Despite the seriousness of
      these allergies, the prevalence of peanut and TN allergy in the general
      population is unknown. OBJECTIVE: We sought to determine the prevalence of peanut
      and TN allergy among the general population of the United States. METHODS: We
      used a nationwide, cross-sectional, random digit dial telephone survey with a
      standardized questionnaire. RESULTS: A total of 4374 households contacted by
      telephone participated (participation rate, 67%), representing 12,032
      individuals. Peanut or TN allergy was self-reported in 164 individuals (1.4%; 95%
      confidence interval [CI], 1.2%-1.6%) in 151 households (3.5%; 95% CI, 2.9%-4.0%).
      The prevalence of reported allergy in adults (1.6%) was higher than that found in
      children under 18 years of age (0.6%). In 131 individuals, details of the
      reactions were obtained. When applying criteria requiring reactions to be typical
      of IgE-mediated reactions (hives, angioedema, wheezing, throat tightness,
      vomiting, and diarrhea) within an hour of ingestion, 10% of these subjects were
      excluded. Among the remaining 118 subjects, allergic reactions involved 1 organ
      system (skin, respiratory, or gastrointestinal systems) in 50 subjects, 2 in 45
      subjects, and all 3 in 23 subjects. Forty-five percent of these 118 respondents
      reported more than 5 lifetime reactions. Only 53% of these 118 subjects ever saw
      a physician for the allergic reaction, and only 7% had self-injectable
      epinephrine available at the time of the interview. The prevalence of peanut and
      TN allergy was adjusted by assuming that 10% of the remaining 33 subjects without
      a description of their reactions would also be excluded and correcting for a 7%
      false-positive rate for the survey instrument. A final "corrected" prevalence
      estimate of 1.1% (95% CI, 1.0%-1.4%) was obtained. CONCLUSIONS: Peanut and/or TN
      allergy affects approximately 1.1% of the general population, or about 3 million
      Americans, representing a significant health concern. Despite the severity of
      reactions, about half of the subjects never sought an evaluation by a physician,
      and only a few had epinephrine available for emergency use.

PMID- 10200002
TI  - Evaluation of apoptosis of eosinophils, macrophages, and T lymphocytes in mucosal
      biopsy specimens of patients with asthma and chronic bronchitis.
AB  - BACKGROUND: Apoptosis regulates inflammatory cell survival, and its reduction
      contributes to the chronicity of an inflammatory process. Apoptosis is controlled
      by suppressing or inducing genes, such as bcl-2 and p53, respectively. OBJECTIVE:
      We sought to assess apoptosis of eosinophils, macrophages, and T lymphocytes in
      bronchial biopsy specimens from asthmatic subjects and to examine its regulation
      by evaluating the expression of B-cell lymphoma leukemia-2 (Bcl-2) and P53
      proteins. We also sought to explore the relationships between cell apoptosis and
      GM-CSF, a cytokine able to increase eosinophil and macrophage survival. METHODS:
      Apoptosis in eosinophils, macrophages, and T lymphocytes was evaluated in
      bronchial biopsy specimens obtained from 30 asthmatic subjects, 26 subjects with
      chronic bronchitis, and 15 control subjects by combining the terminal
      deoxynucleotidyl transferase-mediated dNTP nick end-labeling technique and
      immunohistochemistry. The expression of P53, Bcl-2, and GM-CSF was studied
      through immunohistochemistry by using specific mAbs. RESULTS: The number of
      apoptotic eosinophils and macrophages was lower in subjects with asthma than in
      those with chronic bronchitis (P <.007 and P <.001, respectively) and inversely
      correlated with the clinical severity of asthma (P <.001 and P <.002,
      respectively). Few T lymphocytes were apoptotic in all groups studied. In asthma
      GM-CSF+ cells correlated with the number of nonapoptotic eosinophils and
      macrophages (P =.0001) and with the severity of the disease (P <.003). In asthma
      Bcl-2+ cells were higher than in control subjects and subjects with chronic
      bronchitis (P <.002 and P <.015, respectively), they outnumbered P53+ cells, and
      they correlated with the number of T lymphocytes (P <.001) and with the severity
      of the disease (P <.003). CONCLUSION: Airway inflammation in asthma is associated
      with an enhanced survival of different cell types caused by reduced apoptosis.

PMID- 10200003
TI  - Onset and duration of action of levocabastine nasal spray in atopic patients
      under nasal challenge conditions.
AB  - BACKGROUND: Although prior studies have documented the rapid onset of action of
      topical intranasal levocabastine (LEV), little is known about its duration of
      action under nasal challenge conditions. OBJECTIVES: We sought to assess the
      onset and duration of action of escalating doses of LEV nasal spray by using a
      nasal allergen challenge (NAC) model. METHODS: Eighteen asymptomatic subjects
      with histories of seasonal allergic rhinitis were enrolled into a randomized,
      single-blind, placebo-controlled, dose-ranging crossover study. Each patient was
      randomly assigned to receive single doses of placebo and intranasal LEV 0.1, 0.2,
      and 0.4 mg during 2 parts of the study. In part 1 (onset of action), NAC
      consisted of a single dose of allergen administered 5 minutes after study drug
      treatment. In part 2 (duration of action), NAC consisted of increasing doses of
      allergen administered 0.5, 6, 12, and 24 hours on separate days after study drug
      treatment. Nasal symptom scores (NSSs) and nasal peak expiratory flow rates were
      measured after NAC in both phases of the study. Blood samples for plasma LEV
      concentrations were drawn after each NAC. RESULTS: In part 1, NSSs were
      significantly lower after the administration of LEV 0.1, 0.2, and 0.4 mg compared
      with placebo (P <.05). In part 2, NSSs were significantly lower after LEV doses
      of 0.2 and 0.4 mg compared with placebo at 0.5, 6, 12, and 24 hours after
      treatment (P <.05). The mean provocative dose of allergen required to elicit a
      positive nasal reaction was increased after LEV doses of 0.2 and 0.4 mg at 0.5,
      6, and 12 hours after treatment. Nasal peak expiratory flow rates demonstrated no
      significant differences between LEV and placebo for any doses at any time points.
      Mean plasma LEV concentrations were low (range, 0 to 3. 7 ng/mL) after all doses
      and did not correlate with drug efficacy. CONCLUSIONS: Single intranasal LEV
      doses of 0.1, 0.2, and 0.4 mg significantly reduced the severity of the immediate
      nasal response to allergen when administered 5 minutes before NAC. This
      protective effect against NAC continued to be present 24 hours after
      administration of LEV doses of 0.2 and 0.4 mg. Efficacy in blocking the reaction
      to NAC did not correlate with plasma LEV levels, suggesting that the inhibitory
      effect was due largely to topical rather than systemic effects.

PMID- 10200004
TI  - Washing the dog reduces dog allergen levels, but the dog needs to be washed twice
      a week.
AB  - BACKGROUND: Many asthmatic patients allergic to dogs refuse to part with their
      dog, and it is essential to develop techniques for lowering exposure with a dog
      in the home. OBJECTIVE: This study investigated the effect of dog washing on the
      subsequent recovery of Can f 1 from dog hair clippings and on the airborne
      allergen over a 7-day period. METHODS: Dogs, which had not been washed for at
      least the previous 3 weeks, were washed with a hand-held shower and proprietary
      shampoo. Hair clippings and dander samples from 25 dogs were collected before and
      immediately after washing. After these initial studies, 16 dogs had a small tuft
      of hair clipped from the collar or spinal area before washing and then daily for
      the next 7 days. Air sampling was performed in 5 homes, and the air samples were
      collected (airflow rate, 9 L/min) over an 8-hour period per day on 10 consecutive
      days (3 days of baseline sampling before washing and then 7 consecutive days
      after washing). Can f 1 level was measured by using 2-site ELISA. RESULTS:
      Washing significantly reduced recoverable Can f 1 from clippings (84% reduction:
      from 73 microg/g to 12 microg/g [geometric mean]; P <.0001) and from dander
      samples (86% reduction: from 347 microg/g to 50 microg/g [geometric mean]; P
      <.0001). There was a significant reduction in Can f 1 levels in dog hair over the
      observed 8-day period (F = 18.4, P <. 0001). By using a multiple comparison test,
      this observed significance was found to be due to the difference between the
      baseline levels and those on days 1 and 2 after washing, with no difference in
      the baseline Can f 1 compared with days 3 to 7. Airborne Can f 1 levels showed a
      downward trend, which reached statistical significance when the data were grouped
      into 3 sampling periods as follows: baseline (ie, mean of 3 days before sampling)
      was compared with days 1 to 4 after washing (41% reduction, 95% CI 13%-60%) and
      days 5 to 7 after washing (61% reduction, 95% CI 2%-84%; P =.014). CONCLUSIONS:
      Washing the dog reduces recoverable allergen from dog hair and dander. The dog
      needs to be washed at least twice a week to maintain the reduction in recoverable
      Can f 1 from its hair. Washing the dog achieves a modest reduction in the level
      of airborne Can f 1 in homes with a dog.

PMID- 10200005
TI  - Oral versus intravenous corticosteroids in children hospitalized with asthma.
AB  - BACKGROUND: Previous studies have demonstrated that in the emergency treatment of
      an asthma exacerbation, corticosteroids used in conjunction with beta-agonists
      result in lower hospitalization rates for children and adults. Furthermore,
      orally administered corticosteroids have been found to be effective in the
      treatment of outpatients with asthma. However, similar data in inpatients is
      lacking. OBJECTIVE: The purpose of this study was to determine the efficacy of
      oral prednisone versus intravenous methylprednisolone in equivalent doses for the
      treatment of an acute asthma exacerbation in hospitalized children. METHODS: We
      conducted a randomized, double-blind, double-placebo study comparing oral
      prednisone at 2 mg/kg/dose (maximum 120 mg/dose) twice daily versus intravenous
      methylprednisolone at 1 mg/kg/dose (maximum 60 mg/dose) four times daily in a
      group of patients 2 through 18 years of age hospitalized for an acute asthma
      exacerbation. All patients were assessed by a clinical asthma score 3 times a
      day. The main study outcome was length of hospitalization; total length of stay
      and time elapsed before beta-agonists could be administered at 6-hour intervals.
      Duration of supplemental oxygen administration and peak flow measurements were
      secondary outcome measures. RESULTS: Sixty-six patients were evaluated. Children
      in the prednisone group had a mean length of stay of 70 hours compared with 78
      hours for the methylprednisolone group (P =.52). Children in the prednisone group
      were successfully weaned to beta-agonists in 6-hour intervals after 59 hours
      compared with 68 hours for the methylprednisolone group (P =.47). Patients
      receiving prednisone required supplemental oxygen for 30 hours compared with 52
      hours for the methylprednisolone group (P =.04). CONCLUSION: There was no
      difference in length of hospital stay between asthmatic patients receiving oral
      prednisone and those receiving intravenous methylprednisolone. Because
      hospitalization charges are approximately 10 times greater for intravenous
      methylprednisolone compared with oral prednisone, the use of oral prednisone to
      treat inpatients with acute asthma would result in substantial savings.

PMID- 10200007
TI  - In vivo modulation of glucocorticoid receptor mRNA by inhaled fluticasone
      propionate in bronchial mucosa and blood lymphocytes in subjects with mild
      asthma.
AB  - BACKGROUND: In vivo regulation of the glucocorticoid receptor (GR) by
      glucocorticoids provides a means of modulating sensitivity of targeted cells.
      OBJECTIVE: We sought to determine the in vivo modulation of GR mRNA expression by
      fluticasone propionate (FP) in subjects with mild asthma. METHODS: Ten atopic
      asthmatic subjects were treated with FP 250 microg twice daily for 4 weeks.
      Before and after treatment, the patients underwent fiberoptic bronchoscopy with
      endobronchial biopsy and sampling of venous blood for measurements of GR mRNA
      levels. A solution hybridization assay was used for quantitative analysis of GR
      mRNA. In addition, a 24-hour urinary cortisol excretion and an
      adrenocorticotropic hormone test before and after treatment with FP were
      performed. RESULTS: A high interindividual variation in GR mRNA expression was
      seen. However, we detected a significant reduction of the GR mRNA levels in the
      endobronchial biopsy specimens after FP treatment (36.6 +/- 23.1 and 25.0 +/-
      10.9 amol GR mRNA/microg RNA, respectively; P <.01). In the peripheral blood
      lymphocytes an even more striking downregulation of the GR by its cognate ligand
      was documented (30.3 +/- 26.5 and 8.8 +/- 5 amol GR mRNA/microg RNA,
      respectively; P <.001), possibly reflecting differences in glucocorticoid
      sensitivity between tissues. A small but significant reduction of the 24-hour
      urinary cortisol excretion was observed (233 +/- 109 and 157 +/- 66 nmol/L,
      respectively; P <.01), whereas the feedback regulation of glucocorticoid
      synthesis by means of the hypothalamic-pituitary-adrenal axis as assessed by the
      adrenocorticotropic hormone test remained normal after treatment with FP.
      CONCLUSION: The results in this study confirm the potency of the inhaled
      corticosteroid FP and provide evidence for a considerable tissue-specific
      interindividual variation in the expression of the GR.

PMID- 10200006
TI  - Comparison between nasal provocation tests and skin tests in patients treated
      with loratadine and cetirizine.
AB  - BACKGROUND: The effect of H1-blockers may differ depending on the target organ.
      OBJECTIVE: A double-blind, placebo-controlled study was carried out to compare
      the effect of a 7-day treatment with loratadine (10 mg daily) or cetirizine (10
      mg daily) on nasal challenge with grass pollen grains and skin tests with
      allergen or histamine. METHODS: Twenty-four patients were enrolled, but the
      analysis was carried out on 23. Nasal challenge was carried out by using 5-fold
      increasing numbers of pollen grains. Skin prick tests were done with serial
      concentrations of allergens and 1 concentration of histamine. Patients were
      tested in a cross-over design, with each treatment being administered for the
      previous 7 days and with a 2-week washout period. RESULTS: By comparison with
      placebo, loratadine and cetirizine increased significantly the threshold number
      of pollen grains required to induce a positive nasal challenge (P <.001). There
      was no difference between loratadine and cetirizine. Skin test responses to
      allergen were significantly reduced by loratadine and cetirizine by comparison
      with placebo. Skin test responses to histamine were significantly decreased by
      the 2 H1-blockers, but they were more profoundly decreased by cetirizine than by
      loratadine. CONCLUSIONS: Both H1-blockers reduced similarly allergen-induced skin
      test and nasal challenge responses. Cetirizine was more effective on histamine
      skin test responses.

PMID- 10200008
TI  - Presence of hyperventilation in patients with asthma-like symptoms but negative
      asthma test responses: provocation with voluntary hyperventilation and mental
      stress.
AB  - BACKGROUND: A group of patients reporting asthma-like symptoms but with negative
      asthma tests has been identified. OBJECTIVE: The objective of this study was to
      determine whether hyperventilation might explain these symptoms and whether the
      tests could be used as diagnostic tools. METHODS: A hyperventilation provocation
      test (HVPT), a mental stress test, and the Word Color Conflict Test (WCCT) were
      performed on 10 patients with asthma-like symptoms, 10 patients with asthma, and
      10 healthy subjects. End-tidal PCO 2 (PETCO2) was recorded 10 minutes after the
      HVPT and during the WCCT. Blood pressure, heart rate, and respiratory rate were
      also studied. The Nijmegen symptom questionnaire was used in the assessment of
      symptoms. RESULTS: After the HVPT, the PETCO2 values recovered most slowly in the
      study group, the difference being significant compared with the healthy group (P
      <.01). During the WCCT, the study group had the lowest PETCO2 values at the 10-
      and 15-minute measurements, the difference again being significant compared with
      the healthy group (P <.05). The study group more often experienced symptoms
      before the test than the group with asthma (P <.05) and the healthy group (P
      <.001). The study group recognized significantly more symptoms previously
      experienced during the HVPT than the group with asthma (P <.05) and the healthy
      group (P <.01) and during the WCCT than the healthy group (P <.05). The study
      group showed a negative correlation between the PETCO2 level and the number of
      symptoms after the HVPT at 8 (r = -0-72; P <.05) and 10 minutes (r = -0.76; P
      <.05) and after the WCCT (r = -0.59; P <.05). Blood pressure, heart rate, and
      respiratory rate showed small differences between the groups. CONCLUSION:
      Patients with asthma-like symptoms may experience hyperventilation when provoked.
      Mental stress might be 1 trigger factor. The HVPT and WCCT can be used as
      diagnostic instruments.

PMID- 10200009
TI  - Immunotherapy in children with allergic asthma: effect on bronchial
      hyperreactivity and pharmacotherapy.
AB  - BACKGROUND: Immunotherapy has been shown to reduce allergen sensitivity to
      allergens such as cat and dust mite. The aim of this study was to investigate the
      effect of cat or dust mite immunotherapy on bronchial hyperreactivity and the
      need for inhaled corticosteroids in children with asthma, cat or dust mite
      allergy, and hay fever. SUBJECTS: Twenty-nine children, 7 to 16 years old,
      completed the 3-year study. They were randomly allocated to receive cat/dust mite
      or placebo and birch/timothy immunotherapy. METHODS: Before immunotherapy was
      begun and then once each year, bronchial histamine challenges were performed.
      Bronchial allergen challenge with the perennial allergen was done before and
      after the 3-year study. Pharmacotherapy was given according to a standardized
      protocol. RESULTS: PC20 allergen increased significantly in both the active
      immunotherapy group (P <.001) and in the placebo-pollen group (P <.05). PC20
      histamine increased continuously in the active immunotherapy group (P <.05 and P
      =.002 after 1 and 3 years, respectively) and had also increased after 3 years in
      the placebo-pollen group (P <.05). The difference between the 2 groups was
      significant for PC20 allergen (P =.001) but not for PC20 histamine. There was no
      significant change in the dose of inhaled budesonide needed for symptom control
      in either of the groups. CONCLUSION: Pollen immunotherapy combined with inhaled
      corticosteroids results in improvement of both cat/dust mite bronchial
      sensitivity and hyperresponsiveness to histamine. The combination of cat or dust
      mite, pollen immunotherapy, and inhaled budesonide enhances this improvement. Cat
      immunotherapy also induces cat allergen tolerance.

PMID- 10200010
TI  - The safety and efficacy of nebulized levalbuterol compared with racemic albuterol
      and placebo in the treatment of asthma in pediatric patients.
AB  - BACKGROUND: Limited dose-response information is available for nebulized beta2 
      agonists, especially in young children. OBJECTIVE: The purpose of this study was
      to determine the safety and efficacy of increasing doses of nebulized
      levalbuterol (Xopenex; the pure R-isomer of racemic albuterol) and racemic
      albuterol compared with placebo in the treatment of asthma in pediatric patients.
      METHODS: In this randomized, double-blind, crossover study, children (aged 3 to
      11 years) with asthma (resting FEV1 50% to 80% of predicted normal [Polgar's]
      values) were treated with either levalbuterol, racemic albuterol, or placebo.
      Eligible subjects underwent a screening visit followed by 4 treatment visits. At
      each treatment visit, serial pulmonary function tests were completed before and
      after the treatment; plasma was collected to determine enantiomer levels, and
      safety was evaluated. RESULTS: Five 3- to 5-year-old patients and twenty-eight 6-
      to 11-year-old patients completed the study, and a total of 87 doses of
      levalbuterol were administered. In the 6- to 11-year-old group, all doses of
      levalbuterol were significantly greater than placebo in peak change and percent
      peak change in FEV1 and area under the FEV1 versus time curve (P <.05). The FEV1
      values over the 8-hour study period were similar for levalbuterol 0.31 and 0.63
      mg and racemic albuterol 2.5 mg and were greatest after levalbuterol 1.25 mg.
      Median plasma levels of R-albuterol depended on dose and were 0.4, 0.7, 1.2, and
      1.0 after levalbuterol 0.31 mg, 0.63 mg, and 1.25 mg and racemic albuterol 2.5
      mg, respectively. All patients in the 2.5-mg racemic albuterol arm had measurable
      plasma levels of S-albuterol, although S-albuterol levels were undetectable in
      most patients in the levalbuterol arms. In a few patients who received
      levalbuterol, S-albuterol levels were detected, which was likely because of the
      use of racemic albuterol as a concomitant medication. All active treatments were
      well tolerated. beta-Mediated changes in heart rate, potassium, and glucose were
      dose dependent for all active treatment groups. CONCLUSION: Levalbuterol caused a
      significantly greater increase in FEV1 than placebo, and FEV1 values were
      comparable with or better than those observed with racemic albuterol. beta
      Mediated side effects were lower for an equipotent dose of levalbuterol when
      compared with racemic albuterol. Treatment with levalbuterol resulted in plasma
      levels that were dose dependent and had an approximate correlation with
      pharmacodynamic parameters.

PMID- 10200011
TI  - Effects of fluticasone propionate, triamcinolone acetonide, prednisone, and
      placebo on the hypothalamic-pituitary-adrenal axis.
AB  - BACKGROUND: Many clinicians are reluctant to prescribe inhaled corticosteroids
      because of concerns over potential effects on the hypothalamic-pituitary-adrenal
      axis. OBJECTIVE: The purpose of this study was to compare the adrenal responses
      to 6-hour cosyntropin infusion after treatment with fluticasone propionate
      aerosol, triamcinolone acetonide aerosol, prednisone, and placebo for 4 weeks, a
      sufficient time interval to assess any effects on the adrenal response to stress.
      METHODS: This double-blind, triple-dummy, randomized, placebo-controlled study
      was conducted in 128 patients to evaluate adrenal response to 6-hour cosyntropin
      infusion (a clinically relevant method for evaluating adrenal function) after 28
      days of treatment with fluticasone propionate aerosol 88 microg or 220 microg
      twice daily, triamcinolone acetonide aerosol 200 microg 4 times daily or 400
      microg twice daily, prednisone 10 mg once daily, and placebo. RESULTS: After 28
      days of treatment, mean plasma cortisol response to cosyntropin over 12 hours
      after initiation of the 6-hour infusion was similar among fluticasone,
      triamcinolone, and placebo groups; cortisol response was significantly (P <.05)
      reduced after treatment with prednisone compared with the other treatment groups.
      Mean 8-hour area under the plasma cortisol concentration-time curves and peak
      plasma cortisol concentrations were significantly (P </=.003) lower with
      prednisone than any other treatment; no significant differences were noted
      between placebo and either of the fluticasone groups in any assessment. Mean
      reductions from baseline in area under the plasma cortisol concentration time
      curves and peak cortisol concentrations were significantly (P <.05) greater with
      triamcinolone 400 microg twice daily compared with placebo. CONCLUSION: These
      results suggest that fluticasone propionate at therapeutic doses has effects on
      the hypothalamic-pituitary-adrenal axis comparable to that of placebo and has
      significantly less effect than prednisone as measured by 6-hour cosyntropin
      infusion after 28 days of treatment.

PMID- 10200012
TI  - Increased production of IFN-gamma and cysteinyl leukotrienes in virus-induced
      wheezing.
AB  - BACKGROUND: An imbalance of production of T-helper lymphocyte cytokines, favoring
      overproduction of IL-4, is believed to be important in the pathogenesis of
      allergic asthma. However, less is known about the cytokine response in virus
      induced wheezing, which is a major cause of morbidity in asthma. OBJECTIVE: We
      undertook this study to determine the magnitude of IFN-gamma, IL-4 and IL-10, and
      leukotriene (LT) responses in infants and children with virus-induced wheezing.
      METHODS: We measured the concentrations of IFN-gamma, IL-4 and IL-10, and
      cysteinyl LTs in respiratory secretions of 82 infants and young children during
      acute episodes of virus-induced wheezing. Control subjects were 47 infants and
      children with uncomplicated upper respiratory infections and 18 normal healthy
      infants. RESULTS: Ratios of IFN-gamma to IL-4 were higher (due to increased
      quantities of IFN-gamma) in subjects with wheezing than in those with upper
      respiratory infection alone (P =. 003). Quantities of LTs were also increased in
      wheezing subjects in comparison with those with upper respiratory infections (P
      =.009). There was a significant correlation between measured concentrations of
      IFN-gamma and LTs (correlation coefficient =.451, P =.007). Quantities of IL-4
      were slightly suppressed in the wheezing groups. CONCLUSIONS: An imbalance
      favoring overproduction of IFN-gamma appears to be associated temporarily with
      virus-induced wheezing. A possible mechanism is the enhanced release of LTs from
      eosinophils or mast cells after sensitization by IFN-gamma.

PMID- 10200013
TI  - Selective antipolysaccharide antibody deficiency associated with peripheral blood
      CD5+ B-cell predominance.
AB  - BACKGROUND: Primary humoral deficiencies vary from complete absence of B cells
      and/or serum immunoglobulin to lacunar deficits involving specific antibody
      responses to polysaccharides. OBJECTIVES: We compared the B-cell CD5 expression
      in patients with selective antipolysaccharide antibody deficiencies (SPADs),
      common variable immunodeficiency (CVID), and IgG subclass deficiency and in
      normal control subjects. METHODS: Five patient populations were evaluated: (1)
      patients with severe SPAD (no protective serologic postvaccine response to any of
      12 polysaccharide antigens tested); (2) patients with intermediate SPAD
      (diminished response to polysaccharide antigens and adequate response to 1 to 3
      of 12 serotypes tested); (3) patients with IgG subclass deficiency; (4) patients
      with CVID; and (5) age-matched control subjects. Blood was collected from all
      patients and evaluated by using flow cytometry. Results were compared by using
      the Student t test. RESULTS: Patients with severe SPAD deficiencies had a marked
      predominance of CD5+ B cells in the peripheral blood (93% to 97% of total B
      cells, n = 2). The intermediate SPAD group had a mean CD5+ B-cell percentage that
      was significantly higher than that of the age-matched control group (87. 4%, n =
      7, vs 52.5%, n = 20; P =.007). Patients with CVID and IgG subclass deficiency had
      mean CD5+ B-cell percentages that were similar to those of the age-matched
      control subjects. CONCLUSIONS: Our studies demonstrate that patients with SPAD
      had a markedly increased percentage of CD5+ B cells in the peripheral blood as
      compared with age-matched control subjects and patients with other humoral
      deficiencies. This observation suggests that an association may be present
      between CD5+ B-cell predominance and SPAD.

PMID- 10200014
TI  - The human recombinant histamine releasing factor: functional evidence that it
      does not bind to the IgE molecule.
AB  - BACKGROUND: We have previously shown that the human recombinant histamine
      releasing factor (HrHRF) caused histamine release from a subset of basophils from
      donors with allergy, and this release seemed to be dependent on the presence of a
      certain type of IgE, termed IgE+. IgE molecules that did not support HrHRF
      induced histamine release were termed IgE-. However, subsequently we demonstrated
      that HrHRF primes anti-IgE-antibody-induced histamine release from all basophils,
      irrespective of the type of IgE on the cell surface. OBJECTIVE: Because these
      data suggested that HrHRF does not exert its biologic effects by binding to IgE,
      but rather that it interacted with a surface receptor on the basophil, we wanted
      to obtain functional evidence that HrHRF did or did not bind to the IgE molecule.
      METHODS: The rat basophilic leukemia cell line (RBL-SX38), which has been
      transfected to express a functional human FcepsilonRI (alpha-, beta-, and gamma
      chains of the receptor) in addition to the normal rat FcepsilonRI, was used. The
      presence of the human FcepsilonRI receptor enables these cells to be sensitized
      with human IgE. Cells were passively sensitized with 1000 ng/mL human IgE+ or
      1000 ng/mL human IgE- for 60 minutes at 37 degrees C. Unsensitized cells served
      as a control. After the cells were washed, 1 x l0(5) cells were stimulated in the
      presence of 1 mmol/L Ca2+ with 0.1 microg/mL anti-IgE, 40 microg/mL HrHRF, or 40
      microg/mL mouse recombinant HRF (MrHRF), which has 96% homology to HrHRF.
      RESULTS: Mean anti-IgE-induced histamine release was 33% +/- 15%, and there was
      no difference between IgE+ sensitization (32% +/- 12%) and IgE- sensitization
      (34% +/- 18%). However, in contrast to human basophil experiments, neither HrHRF
      (0% +/- 0%) nor MrHRF (3% +/- 5%) caused histamine release in RBL cells
      sensitized with IgE+. In addition, priming the transfected RBL-SX38 cells or the
      parental cell line, RBL-2H3 cells, with HrHRF or MrHRF did not increase anti-IgE
      induced histamine release. CONCLUSION: The results indicate that HrHRF does not
      bind to IgE, either IgE+ or IgE-. Therefore it appears likely that rHRF signals
      through its own specific receptor, which is not expressed or functional on RBL
      SX38 or RBL-2H3 cells, but which seems to be expressed on basophils of atopic and
      nonatopic donors.

PMID- 10200015
TI  - Enhanced expression of fas ligand (CD95L) on T cells after segmental allergen
      provocation in asthma.
AB  - BACKGROUND: Little is known about the termination of the T-cell driven
      inflammation found in patients with allergic asthma. OBJECTIVE: Because signals
      delivered through Fas/Fas ligand can lead to T-cell apoptosis, we investigated
      the expression of Fas and Fas ligand on peripheral blood- and bronchoalveolar
      lavage fluid (BALF)-derived T cells and the percentage of apoptotic BALF cells in
      asthma. METHODS: Nine atopic subjects with mild asthma and 9 control subjects
      underwent segmental sham and allergen challenge. Flow cytometry was used to
      determine the T-cell expression of Fas and Fas ligand, and the terminal dUTP nick
      end labeled technique was applied to detect apoptotic BALF cells. RESULTS: In
      asthmatic and control subjects almost all T cells in the BALF expressed Fas
      antigen without changes after saline or allergen challenge. A small percentage of
      T cells in BALF expressed the Fas ligand. In asthmatic subjects, but not in
      control subjects, there was a significant increase in Fas ligand after allergen
      challenge (CD3: 0.8% +/- 0.6% [baseline] vs 3.2% +/- 1.2% [allergen challenge];
      CD4: 1.8% +/- 0.0% vs 4.3% +/- 1.8%; CD8: 2.8% +/- 2.4% vs 9.1% +/- 4.8%) but not
      after saline challenge, with a significant correlation to the percentage of BALF
      eosinophils. Apoptotic BALF cells were localized exclusively in macrophages at a
      very low frequency (0.03% to 0.15%) and without changes after saline or allergen
      challenge in both groups. CONCLUSION: In asthma there is an upregulation of Fas
      ligand on T cells in BALF after allergen challenge. Because there is no evidence
      for increased apoptosis, this phenomenon may reflect antigen-induced T-cell
      activation rather than apoptosis.

PMID- 10200016
TI  - Mast cells express connexins on their cytoplasmic membrane.
AB  - BACKGROUND: Because of the close association between mast cells and fibroblasts
      in the microenvironment and the importance of connexins (Cxs) in fibroblast
      communication with other cells, we hypothesized that mast cells also express Cxs,
      allowing them to similarly communicate with other cells through gap junctions.
      OBJECTIVES: We sought to identify the expression of Cxs (particularly Cx43, Cx32,
      and Cx26) by murine mast cells. METHODS: The expression of Cxs was studied by RT
      PCR, Northern blot analysis, Western blot analysis, flow cytometry, and confocal
      laser scanning microscopy. RESULTS: In this report we demonstrate that murine
      bone marrow cultured mast cells and the growth factor-independent murine mast
      cell line C57, express Cx43 and Cx32 as assessed by RT-PCR, Northern blot
      analysis, Western blot analysis, and flow cytometry, but do not express Cx26. We
      also show, by confocal laser scanning microscopy, that Cx43 localizes to the
      cytoplasmic membrane of mast cells in a pattern similar to that seen in
      fibroblasts. CONCLUSIONS: Mast cells express Cx43 and Cx32, and Cx43 is
      associated with the cytoplasmic membrane, suggesting that mast cells have the
      potential to communicate with other cells in their microenvironment in part
      through gap junctions.

PMID- 10200018
TI  - Relation of latex-specific IgE titer and symptoms in patients allergic to latex.
AB  - BACKGROUND: The relation between latex-specific IgE titer and the type or total
      number of latex-induced symptoms has not been previously investigated. OBJECTIVE:
      We sought to determine the association of latex-IgE in vitro assay results with
      the type, number, or severity of symptoms in patients allergic to latex. METHODS:
      Ninety-one patients with positive histories and positive skin test responses were
      identified as having type I allergy. Data was collected for reported symptoms
      after latex exposure. Symptom severity was quantitated by 2 scores: (1) the total
      number of symptoms to latex exposure and (2) a symptom severity score (3 =
      anaphylaxis, 2 = asthma, and 1 = rhinoconjunctivitis, urticaria, or both). All
      subjects underwent AlaSTAT and CAP tests. RESULTS: AlaSTAT class was associated
      with total number of symptoms (r = 0.32, P <.001) and severity score (r = 0.33, P
      <.002). Similarly, CAP class was associated with both number of symptoms (r =
      0.32, P <. 0001) and severity score (r = 0.31, P <.001). Among the symptoms
      reported, asthma had the strongest association with a positive in vitro IgE assay
      (odds ratio = 6.7 [95% confidence interval = 1.9, 25. 6]), followed by urticaria
      (odds ratio = 1.9 [95% confidence interval = 0.8, 4.6]). Contact dermatitis had
      no statistical association with in vitro assays in this study. AlaSTAT and CAP
      class correlated together significantly (r = 0.58, P <.001). CONCLUSION: Patients
      allergic to latex with higher AlaSTAT or CAP class were more symptomatic.
      Increasing class or titer also predicted more severe symptoms. Higher class of
      either the AlaSTAT or CAP assay to latex was strongly associated with latex
      related asthma and urticaria and marginally associated with latex-related
      rhinoconjunctivitis.

PMID- 10200019
TI  - Exposure-response relationships for work-related sensitization in workers exposed
      to rat urinary allergens: results from a pooled study.
AB  - BACKGROUND: Recent studies in a few industries have shown that the likelihood of
      IgE-mediated sensitization increases with increasing exposure. The shape of the
      exposure-response relationships and modification by age, sex, and smoking habit
      has hardly been studied. OBJECTIVE: The purpose of this study was to determine
      exposure sensitization relationships for rat sensitization and to evaluate the
      influence of atopy, smoking habits, and sex. METHODS: Data from 3 cross-sectional
      studies in The Netherlands, the United Kingdom, and Sweden were used and involved
      1062 animal laboratory workers. Selection criteria were harmonized, and this
      resulted in a study population of 650 animal laboratory workers (60.6% female)
      with less than 4 years of exposure. Air allergen levels were assessed previously
      and converted on the basis of an interlaboratory allergen analysis comparison.
      Available sera were analyzed for the presence of specific antibodies against
      common allergens (house dust mite, cat, dog, and grass and birch pollen) and work
      related allergens (rat and mouse urinary proteins). Questionnaire items on work
      related respiratory symptoms, hours worked with rats per week, job performed,
      smoking habits, and sex were used in this analysis RESULTS: The prevalence of
      work-related sensitization to rat urinary allergens (IgE >0.7 KU/L) was 9.7 % (n
      = 63). Thirty-six of the sensitized workers had work-related symptoms (asthma or
      rhinitis). Two hundred forty-eight workers (38.2%) were atopic (defined as
      specific IgE to 1 of the common allergens). The sensitization rate increased with
      increasing air allergen exposure. Atopic workers exposed to low levels of
      allergen had a more than 3-fold increased sensitization risk compared with
      nonexposed atopic workers. For atopic subjects, the risk increased little with
      increasing exposure, whereas for nonatopic subjects, a steadily increasing risk
      was observed. Smoking and sex did not modify the sensitization risk. CONCLUSION:
      Rat urinary allergen-sensitization risk increased with increasing exposure
      intensity. Workers who were atopic had a clearly elevated sensitization risk at
      low allergen exposure levels.

PMID- 10200017
TI  - Chemical mediators in atopic dermatitis: involvement of leukotriene B4 released
      by a type I allergic reaction in the pathogenesis of atopic dermatitis.
AB  - BACKGROUND: The mediators produced from a type I allergic reaction have not yet
      been able to explain the pathogenesis of atopic dermatitis (AD). OBJECTIVE: The
      purpose of this study was to elucidate the involvement of leukotriene (LT) B4
      produced from a type I allergic reaction in the pathogenesis of AD. METHOD: The
      release of LTB4 was measured both in vitro, in passively sensitized and antigen
      challenged human skin slices, as well as in vivo, in skin chambers on patients
      with AD. RESULTS: LTB4 was released from in vitro human skin by stimulation of
      the antigen (54.9 +/- 14.6 pg/g wet weight of skin by antigen challenge and 28.0
      +/- 11.1 pg/g in control skin, P <.002). Antigen-specific release of LTB4 and
      histamine was also observed in vivo in nonlesional skin from the patients with AD
      by using the skin chamber technique. CONCLUSION: LTB4 release during type I
      allergic reaction in human skin has been determined in vitro. The released LTB4
      possibly contributes to cellular response at the acute inflammatory lesion of AD.

PMID- 10200020
TI  - Association of HLA-DR11 with the anaphylactoid reaction caused by nonsteroidal
      anti-inflammatory drugs.
AB  - BACKGROUND: Several HLA alleles have been associated with asthma induced by
      nonsteroidal anti-inflammatory drugs (NSAIDs). The existence of HLA markers
      linked to other NSAID-induced reactions, such as cutaneous and anaphylactoid
      reactions, has not been established. OBJECTIVE: The purpose of our work was to
      study the HLA-DRB1 and HLA-DQB1 alleles in patients with cutaneous and
      anaphylactoid reactions caused by NSAIDs. METHODS: We have analyzed 114 HLA DRB1
      and 26 HLA-DQB1 alleles in 21 patients with anaphylactoid reactions caused by
      NSAIDs, 47 patients who had exclusively cutaneous reactions during single-blind,
      placebo-controlled oral challenges with NSAIDs, and 167 tolerant control subjects
      (29 of whom had also had an IgE-mediated anaphylaxis to different agents). HLA
      DRB1 and HLA-DQB1 alleles were typed by the polymerase chain reaction sequence
      specific primers method with genomic DNA. RESULTS: The frequency of HLA-DR11
      alleles was 58.8% in the anaphylactoid reaction group, compared with 15.9% in the
      NSAID-tolerant healthy control subjects (OR, 7:3; 95% confidence interval, 2.8
      19.0; P <.02) and 6.3% in the group of the patients with a tolerance for NSAIDs
      and with IgE-mediated anaphylaxis (OR, 18.75; 95% confidence interval, 4.3-81.1;
      P <.004). No differences were observed among HLA-DR11 alleles analyzed. There
      were no significant HLA-DQB1 associations with NSAID-induced anaphylactoid
      reactions. Patients with cutaneous reactions had HLA frequencies that did not
      differ significantly from the tolerant control subjects. CONCLUSION: The HLA
      DRB1*11 alleles showed a positive association with NSAID-induced anaphylactoid
      reactions.

PMID- 10200021
TI  - Thioredoxin treatment increases digestibility and lowers allergenicity of milk.
AB  - BACKGROUND: By resisting digestion in the stomach, the major bovine milk
      allergen, beta-lactoglobulin, is believed to act as a transporter of vitamin A
      and retinol to the intestines. beta-Lactoglobulin has 2 intramolecular disulfide
      bonds that may be responsible for its allergic effects. OBJECTIVE: This study was
      carried out to assess the importance of disulfide bonds to the allergenicity and
      digestibility of beta-lactoglobulin. METHODS: beta-Lactoglobulin was subjected to
      reduction by the ubiquitous protein thioredoxin, which was itself reduced by the
      reduced form of nicotinamide adenine dinucleotide phosphate by means of
      nicotinamide adenine dinucleotide phosphate-thioredoxin reductase. Digestibility
      was measured with a simulated gastric fluid; results were analyzed by SDS-PAGE.
      Allergenicity was assessed with an inbred colony of high IgE-producing dogs
      sensitized to milk. RESULTS: As found for other proteins with intramolecular
      disulfide bonds, beta-lactoglobulin was reduced specifically by the thioredoxin
      system. After reduction of one or both of its disulfide bonds, beta-lactoglobulin
      became strikingly sensitive to pepsin and lost allergenicity as determined by
      skin test responses and gastrointestinal symptoms in the dog model. CONCLUSION:
      The results provide new evidence that thioredoxin can be applied to enhance
      digestibility and lower allergenicity of food proteins.

PMID- 10200022
TI  - Anaphylaxis from yellow fever vaccine.
AB  - BACKGROUND: There are very few reports of anaphylactic reactions to yellow fever
      (YF) vaccine in the literature, and these date from the 1940s. OBJECTIVE: We
      sought to estimate the rate of YF vaccine-related anaphylaxis. METHODS: All
      reports of adverse reactions to YF vaccine submitted to the Vaccine Adverse Event
      Reporting System between 1990 and 1997 were reviewed for those meeting criteria
      for probable or possible anaphylactic reactions. RESULTS: Of 243 reports
      submitted, 40 describe probable or possible anaphylactic reactions. In 22 of
      these 40, YF vaccine was the only vaccine administered. There were 5,236,820
      doses of YF vaccine distributed in the United States during this period. By using
      all 40 cases, the rate of YF vaccine-related anaphylaxis would be 40 in 5,
      236,820 or about 1 in 131,000. In 35 of the reports, information was provided on
      whether previous doses of YF vaccine had been given. In 34 of these 35, the
      reaction occurred after the first dose of YF vaccine, suggesting that vaccine
      constituents other than the viral proteins may have been the allergens. The
      vaccine is grown in chicken embryos and contains gelatin as a stabilizer.
      CONCLUSION: YF vaccine can cause anaphylactic reactions. Persons presenting for
      YF vaccine should be asked if they have had adverse reactions to previous doses
      of this or other vaccines and if they are allergic to eggs, chicken, or gelatin.
      Health care workers administering YF vaccine should be prepared to recognize and
      treat anaphylactic reactions should they occur.

PMID- 10200023
TI  - Association of 3 gene polymorphisms with atopic diseases.
AB  - BACKGROUND: Various peptidases, including angiotensin-converting enzyme (ACE),
      inactivate some inflammatory peptides that are considered to influence the
      pathogenesis of atopic diseases. This enzyme is also involved in the conversion
      or activation of 2 bronchoconstriction mediators: angiotensin II from
      angiotensinogen and endothelin (ET), respectively. OBJECTIVE: We tested a
      hypothesis that asthma or other atopic diseases are associated with
      insertion/deletion ACE, M235T angiotensinogen, and TaqI ET-1 gene polymorphisms.
      METHODS: A case-control approach was used in the study. Healthy subjects (141
      persons) were used as control subjects, and 231 patients with histories of atopic
      asthma, allergic rhinitis, atopic dermatitis, or a combination thereof were
      studied. ACE genotype was determined by PCR, angiotensinogen M235T and ET-1 by
      PCR, and restriction analysis by AspI and TaqI, respectively. RESULTS: We found
      the significant association of the insertion/deletion polymorphism of the ACE, as
      well as that of M235T polymorphism of the angiotensinogen genes, with the group
      of patients with atopic diseases ( P =.0025 and P =.0204, respectively). No
      difference was proved for the intron 4 (position 8000) polymorphism in the ET-1
      gene when comparing the atopic patients with the control group (P =.1774). A
      significant difference was found between groups of patients with both asthma and
      rhinitis and patients without both respiratory atopic diseases (P =.0033).
      CONCLUSION: It follows that the examined polymorphisms in the genes for ACE,
      angiotensinogen, and ET-1 could participate in the etiopathogenesis of atopic
      diseases.

PMID- 10200024
TI  - Is sensitization to Alternaria alternata a risk factor for severe asthma? A
      population-based study.

PMID- 10200025
TI  - Acquired angioedema associated with chronic hepatitis C.

PMID- 10200026
TI  - Refractory exacerbations of hereditary angioedema with associated Helicobacter
      pylori infection.

PMID- 10200027
TI  - Same drug, different outcomes in the environmental exposure unit.

PMID- 10200030
TI  - By the way, doctor... Can exercise help prevent prostate symptoms? This is a
      claim made in a mailing by a local health club, and I want to know if it's true.

PMID- 10200029
TI  - Aspirin: real benefits, but real risks, too.

PMID- 10200031
TI  - Coping. You're not alone when it comes to loneliness.

PMID- 10200032
TI  - Urinary incontinence. Putting an end to the embarrassment.

PMID- 10200034
TI  - Violence and aggression in psychiatric patients.

PMID- 10200035
TI  - What others don't know.

PMID- 10200033
TI  - Dietary fat, breast cancer link is challenged.

PMID- 10200036
TI  - What are the advantages and disadvantages of using different providers for
      psychotherapy and drug treatment?

PMID- 10200038
TI  - Poswillo updated?

PMID- 10200037
TI  - Requirement of Ca2+ for aflatoxin production: inhibitory effect of Ca2+ channel
      blockers on aflatoxin production by Aspergillus parasiticus NRRL 2999.
AB  - Aflatoxin production by Aspergillus parasiticus NRRL 2999 was inhibited when Ca2+
      channel blockers, i.e., verapamil and diltiazem (> 1 mmol 1(-1)), were included
      in the culture medium. Inhibition was not accompanied by growth inhibition, nor
      was the [14C]-glucose uptake by the organism altered. However, both the compounds
      inhibited [14C]-acetate incorporation into aflatoxin B1 in a dose-dependent
      manner and decreased sporulation of the organism. Even though a nutritional role
      for Ca2+ has not been demonstrated unequivocally in fungi, the present study
      suggests the importance of Ca2+ in the production of these secondary metabolites.

PMID- 10200039
TI  - Diploma regulation.

PMID- 10200040
TI  - Proceedings of the Genoa Meeting of the Society for Research into Hydrocephalus
      and Spina Bifida, 1998.

PMID- 10200041
TI  - [Diversity and Unity in Surgery: Humanity and Science. Proceedings of the 115th
      Congress of the German Society for Surgery. Berlin, 28 April-2 May, 1998].

PMID- 10200042
TI  - Lichen planus as a side effect of HBV vaccination.

PMID- 10200043
TI  - Potential risk of birth defects after acitretin discontinuation.

PMID- 10200044
TI  - Proceedings of the 3rd Central European Transplant Conference. Wroclaw, Poland,
      December 15-17, 1997.

PMID- 10200045
TI  - Designing an alternative career ladder for library assistants.

PMID- 10200046
TI  - Virtual or actual: the term library is enough.

PMID- 10200047
TI  - From the past: historical resources and the virtual library.

PMID- 10200048
TI  - Balancing divergent expectations.

PMID- 10200049
TI  - Eileen R. Cunningham.

PMID- 10200050
TI  - Genetic findings in congenital bilateral aplasia of vas deferens patients and
      identification of six novel mutatations. Mutations in brief no. 138. Online.
AB  - Congential bilateral aplasia of vas deferens (CBAVD), a form of male sterility,
      has been suggested to represent a "genital" form of cystic fibrosis (CF), as
      mutations in the CFTR gene have been identified in most patients with this
      condition. Interestingly, the 5T allele in intron 8 appeared to be the most
      frequent mutation associated with CBAVD. However, the molecular basis of CBAVD is
      not completely understood. We have analysed the complete coding and flanking CFTR
      sequences by PCR-DGGE in 64 men with CBAVD from southern France with the aim to
      list any sequence alteration. Fourty-two of the 64 patients (65.6%) had mutations
      on both copies of the CFTR gene, including one patient with two mutations in the
      same copy (DF508 + A1067T). The 5T allele was present in 21/64 cases (33%). Six
      of the 28 different mutations identified in this study had never been described
      previously, and appeared to be specific to CBAVD (P111L, M244K, A1364V, G544V,
      2896insAG,-33G->A).

PMID- 10200051
TI  - Gorlin syndrome: identification of 4 novel germ-line mutations of the human
      patched (PTCH) gene. Mutations in brief no. 137. Online.
AB  - PTCH, the human homologue of the Drosophila segment polarity gene, patched, has
      been identified as the gene responsible for Gorlin or nevoid basal cell carcinoma
      syndrome (NBCCS). We report here the characterization of four novel mutations in
      the human PTCH gene in germ-line DNA from Gorlin patients. All mutations lead to
      truncation of the predicted protein product. Also included is a list of putative
      polymorphic nucleotide postions in the sequence covered by published primers.

PMID- 10200052
TI  - A novel point mutation in a splice acceptor site of intron 1 of the human low
      density lipoprotein receptor gene which causes severe hypercholesterolemia: an
      unexpected absence of exon skipping. Mutations in brief no. 139. Online.
AB  - Familial hypercholesterolemia (FH) is a genetic disorder caused by mutations in
      the low density lipoprotein (LDL)-receptor gene. We found a new mutation in the
      splice acceptor site of intron 1 of the LDL receptor gene, which is designated as
      68-1 G->C according to the nomenclature suggested by Beaudet and Tsui (1993), in
      a Japanese FH homozygote. She was born from consanguineous marriage and has this
      mutation as a true homozygous form. Her cultured fibroblasts showed no LDL
      receptor protein synthesis. This mutation caused activation of a cryptic splice
      acceptor side in the downstream exon 2, leading to frameshift and appearance of
      premature in-frame stop codon. The mutation was detected by Dde I restriction
      enzyme. The identical mutation was not found among 24 patients with homozygous
      and 120 patients with heterozygous FH. The mutation was very rare among the
      Japanese population.

PMID- 10200053
TI  - A de novo missense mutation (R1623Q) of the SCN5A gene in a Japanese girl with
      sporadic long QT sydrome. Mutations in brief no. 140. Online.
AB  - Two missense mutations and a nine-nucleotide deletion of the cardiac sodium
      channel (SCN5A) gene have been shown to cause long QT syndrome (LQTS) in several
      familial cases. We identified a novel missense mutation (R1623Q) of the SCN5A
      gene in a Japanese girl with sporadic LQTS. We used polymerase chain reaction,
      single-strand conformation polymorphism analysis and DNA sequence analysis to
      identify a mutation of the SCN5A gene in the patient. A single nucleotide
      substitution of guanine to adenine, in codon 1612, changed the coding sense of
      the SCN5A from arginine to glutamine (R1623Q) in the S4 segment of domain IV
      which is a highly conserved region of the SCN5A. This mutation was not identified
      in the unaffected biological parents and brother of the patient, and 100 normal,
      unrelated individuals. This finding is the first evidence of a de nova mutation
      in SCN5A associated with LQTS.

PMID- 10200054
TI  - Missense mutation in exon 11 (Codon 378) of the presenilin-1 gene in a French
      family with early-onset Alzheimer's disease and transmission study by mismatch
      enhanced allele specific amplification. Mutations in brief no. 141. Online.
      besancon@rockefeller1.univ.lyon1.fr.
AB  - Mutations in the presenilin-1 (PS1) gene account for the majority of familial
      early-onset Alzheimer's disease (EOAD) cases. We screened the coding part of the
      PS1 gene for the present of mutations in a French family with EOAD, using single
      strand conformation polymorphism (SSCP) analysis. Patients in the pedigree showed
      a missense mutation in exon 11 of the PS1 gene involving a transition of G to A,
      altering glycine to glutamate at codon 378. The cosegregation of the mutation
      with EOAD in the family was studied by allele specific amplification, enhanced by
      the introduction of a mismatch at the penultimate position near the 3' primer
      end. The mutation has not been described before and is located within the third
      large cytoplasmic loop and may lead to the appearance of a short additional a
      helix.

PMID- 10200055
TI  - Mutation sharing, predominant involvement of the MLH1 gene and description of
      four novel mutations in hereditary nonpolyposis colorectal cancer. Mutations in
      brief no. 144. Online.
AB  - Worldwide, the DNA mismatch repair genes MSH2 and MLH1 account for a major share
      and almost equal proportions of hereditary nonpolyposis colorectal cancer
      (HNPCC). Furthermore, the predisposing mutation usually varies from kindred to
      kindred. In this study, we screen 29 verified or putative HNPCC kindreds from
      Finland for mutations in these two genes and found 8 different mutations, 7 in
      MLH1 and 1 in MSH2, occurring in 13 families. Four of these mutations were novel.
      Altogether, we have to date studied 81 kindreds for mutations and 12 different
      mutations in 52 families have been identified, 10 in MLH1 and 2 in MSH2. These
      data show that Finnish HNPCC kindreds are characterized by the predominant
      involvement of MLH1 (49/52, 94% of the families) and a high rate of shared
      mutations (5/12, 42%) offering unique possibilities for mutation screening for
      both research and diagnostic purposes.

PMID- 10200056
TI  - Seven novel mutations in the adenosine deaminase (ADA) gene in patients with
      severe and delayed onset combined immunodeficiency: G74C, V129M, G140E, R149W,
      Q199P, 462delG, and E337del. Mutations in brief no. 142. Online.
AB  - The degree of immunodeficiency associated with deficiency of adenosine deaminase
      (ADA) is variable. Most patients are infants with severe combined
      immunodeficiency (SCID), but in about 20 percent immune dysfunction becomes
      manifest later in childhood ("delayed-onset"); several patients with "late" or
      "adult" onset of immune dysfunction have been diagnosed at 15-39 years. Over 40
      ADA gene mutations have thus far been identified. To better define the genotype
      phenotype relationship, we report 7 novel ADA mutations, including 5 missense
      mutations (G74C, V129M, G140E, R149W, Q199P) and two short deletions (462delG,
      E337del). These were identified among 7 patients (3 with SCID and 4 with delayed
      onset). A homozygote for 462delG had SCID, whereas patients homozygous or
      heterozyous for V129M had delayed-onset. Two other delayed-onset patients, one
      heterozygous for G74C and the other for Q199P, each had a second allele carrying
      the previously reported "severe" mutation G216R. These findings are consistent
      with previous observations suggesting that, in general, SCID occurs when both
      alleles eliminate ADA function, and a milder phenotype when at least one allele
      can supply a low level of function.

PMID- 10200058
TI  - A new informative Alw 26 I polymorphism in exon 10 of the human low density
      lipoprotein receptor gene. Application to prenatal diagnosis. Mutations in brief
      no. 145. Online.
AB  - Using DNA sequencing of the coding and exon flanking regions of the low density
      lipoprotein receptor (LDLR) gene we identified an Alw26 I site in exon 10 by a
      transition G142A. The alleles are represented by one uncut fragment (A1=108bp) or
      two fragments (A2=82bp and 26 pb). Two other fragments (72bp and 16bp) were
      systematically found within the amplified product. The alleles were detected in
      157 unrelated French Caucasians with A1 frequency = 0.58 and A2=0.42. The
      observed heterozygoty was 44.5%. Homozygous familial hypercholesterolemie (FH)
      has a severe clinical picture leading to death during childhood. Because it is
      very informative, the present polymorphism was very useful as genetic marker for
      clinical diagnois and counseling as we described in linkage analysis at the LDLR
      locus for prenatal diagnosis in a fetus who could inherit two LDLR mutant alleles
      from FH heterozygote parents.

PMID- 10200057
TI  - Two novel mutations in exon 11 of the PAH gene (V1163del TG and P362T) associated
      with classic phenylketonuira and mild phenylketonuria. Mutations in brief no.
      143. Online.
AB  - PKU is one of the commonest genetic disease in man, affecting 1/10,000
      individuals. It presents a wide phenotypical spectrum, from classic PKU to
      moderate Hyperpheylalaninemia depending on the residual enzymatic activity. Two
      novel mutations 1163/1164delTG and P362T in exon 11 have been detected during the
      mutational screening of the PAH gene in 84 families. 1163/1164delTC can be
      confused with V388M if the mutational screening is performed with BsaAI
      restriction enzyme, this mutation in heterozigosis presents a moderate phenotype.
      P362T mutation in heterozigosis with V388M shows a classical PKU phenotype. We
      report here two new mutations in exon 11 of the PAH gene (GenBank U49897),
      V1163delTG and P362T (using cDNA sequence), detected during the analysis of 57
      PKU and 36 HPA patients belonging to 84 unrelated families detected under a
      neonatal screening program performed in Catalonia.

PMID- 10200059
TI  - Novel acceptor splice site mutation in the invariant AG of intron 6 of alpha
      galactosidase A gene, causing Fabry disease. Mutations in brief no. 146. Online.
AB  - We found a novel acceptor splice site mutation in the invariant AG of intron 6 of
      alpha-galactosidase A (alpha-Gal A) gene (IVS6-1G->A) in a patient with Fabry
      disease by sequencing of genomic DNA. Sequencing of RT-PCR revealed the deletion
      of first base pair (c909del) of exon 7 in mRNA and a frameshift resulting in
      premature termination. This mutation gives rise to a rare aberrant splicing
      (Simultaneous 3' destruction and 3' creation).

PMID- 10200060
TI  - Pre- and postgame macronutrient intake of a group of elite Australian football
      players.
AB  - This study describes pre- and postcompetition mean energy and macro nutrient
      intakes of 40 elite Australian Football players. Carbohydrate intake, expressed
      both as a percentage of total energy intake (En%) and as grams per kilogram of
      body mass (g/kg BM). Pregame carbohydrate intake (53.6% En) was significantly
      greater (p < .01) than postgame (49.7% En). However, expressed as g/kg BM, pre-
      and postgame macronutrient intakes did not differ significantly. Protein and fat
      intakes (as g/kg BM) fell within guidelines, whereas energy intake (13.2 MJ/day
      or 153.8 kJ/kg BM) was lower than expected. Results suggest that for athletes
      engaging in endurance team sports where body mass and energy requirements vary
      considerably, carbohydrate recommendations are more appropriately expressed as
      g/kg BM rather than En %.

PMID- 10200061
TI  - Energy and nutrient status of amenorrheic athletes participating in a diet and
      exercise training intervention program.
AB  - Chronic energy deficit is one of the strongest factors contributors to exercise
      induced menstrual dysfunction. In such cases, macro- and micronutrient intakes
      may also be low. This study presents the results of a diet and exercise training
      intervention program. designed to reverse athletic amenorrhea, on improving
      energy balance and nutritional status in 4 amenorrheic athletes. The 20-week
      program provided a daily sport nutrition supplement and 1 day of rest/week. The
      program increased protein intakes for the 3 athletes with a protein deficit to
      within the recommended levels for active individuals. Micronutrient intakes
      increased, as did serum concentrations of vitamin B12, folate, zinc, iron, and
      ferritin. These results indicate that some amenorrheic athletes have poor
      nutritional status due to restricted EIs and poor food selections. A sport
      nutrition supplement may improve energy balance and nutritional status in active
      amenorrheic women.

PMID- 10200062
TI  - Publication of adverse events in exercise studies involving nutritional agents.

PMID- 10200063
TI  - The efficacy of carbohydrate supplementation and chronic high- carbohydrate diets
      for improving endurance performance.
AB  - Carbohydrate (CHO) is the body's most limited fuel and the most heavily
      metabolized during moderate-intensity exercise. For this reason it is recommended
      that endurance athletes consume a high-CHO diet (8-10 g CHO . kg body weight-1 .
      day-1) to enhance training and performance. A review of the literature supports
      the benefits of CHO supplementation on endurance performance. The benefits of
      chronic high-CHO diets on endurance performance are not as clear. Recent evidence
      suggests that a high-CHO diet may be necessary for optimal adaptations to
      training. However, the paucity of date in this area precludes any concrete
      conclusions. The practicality of high-CHO diets is not well understood. The
      available evidence would indicate that a high-CHO diet is the best dietary
      recommendation for endurance athletes.

PMID- 10200064
TI  - Proceedings of the 2nd European Pesticide Residue Workshop, EPRW98. Almeria,
      Spain, 24-27 May 1998.

PMID- 10200065
TI  - [The development of research in the field of experimental mycology (1978-1998)].

PMID- 10200066
TI  - [The 25th anniversary of the development of mycoplasmology in the D. K.
      Zabolotnyi Institute of Microbiology and Virology of the National Academy of
      Sciences of Ukraine].

PMID- 10200067
TI  - Proceedings of the 13th Annual General Meeting of the Italian Association for the
      Study of Glaucoma. Rapallo, Italy, 13-14 March 1998.

PMID- 10200068
TI  - Proceedings of the 7th Scientific Meeting of the Pacific Rim College of
      Psychiatrists. Fukuoka, Japan.

PMID- 10200069
TI  - Making cents out of caring for patients.

PMID- 10200070
TI  - New types of antimicrobial compounds produced by Lactobacillus plantarum.
AB  - New types of antimicrobial compounds were identified in the culture filtrate of
      Lactobacillus plantarum VTT E-78076. Activity was detected in the low molecular
      mass fraction separated by gel chromatography. This fraction totally inhibited
      the growth of the Gram-negative test organism, Pantoea agglomerans (Enterobacter
      agglomerans) VTT E-90396. Characteristic compounds from this fraction were
      identified by GC/MS-analysis and the identification was confirmed using pure
      commercial reference compounds in identical chromatographs and in antimicrobial
      tests. The active fraction included benzoic acid (CAS 65-85-0), 5-methyl-2,4
      imidazolidinedione (CAS 616-03-5, methylhydantoin), tetrahydro-4-hydroxy-4-methyl
      2H- pyran-2-one (CAS 674-26-0, mevalonolactone) and 3-(2-methylpropyl)-2,5
      piperazinedione (CAS 5845-67-0, cyclo(glycyl-L-leucyl)). These compounds in
      concentrations of 10 ppm inhibited growth of the test organism by 10-15% when
      acting separately, but 100% when all were applied together with 1% lactic acid.
      The inhibition was 40% by 1% lactic acid alone. The compounds were also active
      against Fusarium avenaceum (Gibberella avenacea) VTT-D-80147. The inhibition was
      10-15% by separate compounds in concentrations of 10 ppm and maximally 20% in
      combinations. Fungal growth was not inhibited by lactic acid. Inhibition by
      unfractionated Lact. plantarum culture filtrate was 37% and by the low molecular
      mass fraction, 27%.

PMID- 10200071
TI  - Franco-Belge Consensus Conference on Reflux gastro-esophagitis in the adult-
      diagnosis and treatment. Paris, France, 21-22 January 1999. Proceedings.

PMID- 10200072
TI  - A geriatric educational resource.

PMID- 10200073
TI  - Application of stable isotopes in clinical medicine. BIOMED1--Project PL93-1239.

PMID- 10200075
TI  - Dreaming with the dream team in the Netherlands.

PMID- 10200074
TI  - Workshop EFP 1998: diet, foraging behaviour and time budgets in non-human
      primates: how field studies may help improve the welfare of captive primates.
      European Federation for Primatology.

PMID- 10200076
TI  - Excellent article on Web search tools.

PMID- 10200077
TI  - Cannot separate spiritual from physical.

PMID- 10200078
TI  - Ocular cicatricial pemphigoid.
AB  - CP is a systemic disease of presumed autoimmune etiology that may involve the
      skin, conjunctiva, or any mucosal surface. As many patients present with ocular
      symptoms, ophthalmologists must inquire about signs of potential life-threatening
      esophageal and laryngeal involvement. Ocular involvement is a bilateral chronic
      cicatricial conjunctivitis that may result in fornix foreshortening, symblepharon
      formation, trichiasis, and entropion and keratinization of the eyelids and
      conjunctiva. These mechanical factors are responsible for progressive scarring
      and vascularization of the ocular surface. Successful systemic treatment of the
      autoimmune disease is now available; however, the condition often is not
      diagnosed until significant structural damage to the ocular adnexa has occurred.
      Our ability to rehabilitate visually patients with advanced disease by
      penetrating keratoplasty and associated techniques remains extremely limited.
      Hence, the focus of treatment in OCP should be on early detection of the disease,
      including conjunctival biopsy, prompt systemic treatment to prevent disease
      progression, and early aggressive treatment of secondary eyelid and conjunctival
      abnormalities to avoid the blinding keratopathy so prevalent in this disease.

PMID- 10200079
TI  - Culex pipiens in London Underground tunnels: differentiation between surface and
      subterranean populations.
AB  - Genetic variation was quantified between surface-dwelling populations of Culex
      pipiens and the so-called molestus form found in the London Underground (the
      Underground) railway system. The molestus form is a commercially important biting
      nuisance and in the southern part of its range is also a disease vector. The
      surface and subterranean populations were genetically distinct, with no evidence
      of gene flow between closely adjacent populations of the different forms, whereas
      there was little differentiation between the different populations of each form.
      The substantially reduced heterozygosity in the Underground populations and the
      allelic composition suggest that colonization of the Underground has occurred
      once or very few times. Breeding experiments show compatibility between the
      Underground populations but not with those breeding above ground. There is
      evidence of greater gene flow and a mixing of molestus and pipiens traits in the
      south of the species range. This paper considers the processes that may allow
      establishment of reproductive isolation in the north of the species range but not
      in the south.

PMID- 10200080
TI  - The Catherine wheel. For Michael O' Reilly.

PMID- 10200081
TI  - [Molecular biology and genetics in the field of otorhinolaryngology--molecular
      biology of allergy].

PMID- 10200082
TI  - The glossary of prosthodontic terms.

PMID- 10200083
TI  - Super germs solution.

PMID- 10200084
TI  - NMA's clinical trials program.

PMID- 10200086
TI  - [Significance of plasma fibronectin and CH50 determination in the evaluation of
      tissue responses of medical materials].

PMID- 10200085
TI  - [F.B. Fokht (1848-1930) and his scientific contribution to the development of
      clinical medicine (on 150th anniversary of his birth)].

PMID- 10200087
TI  - [Experimental study on efficacy of the treatment of a cut surface of a lung by
      using a newly developed synthetic absorbent sealant, Advaseal].

PMID- 10200088
TI  - [What are the factors determining authorship? An inquiry anong authors from the
      Nederlands Tijdschrift voor Geneeskunde].

PMID- 10200089
TI  - New Antiepileptic Drugs in Psychiatry. Symposium Proceedings. Schloss Elmau,
      Germany, March 27-29, 1998.

PMID- 10200090
TI  - [Diciphering mechanisms for glyco-chain signals--introduction].

PMID- 10200091
TI  - [Basic study on glyco chains].

PMID- 10200092
TI  - [Atypical thoracic pain. Panic disorder].

PMID- 10200093
TI  - Proceedings of the XIII International Symposium on Night and Shift Work. Finland,
      23-27 June 1997.

PMID- 10200094
TI  - [New information sources].

PMID- 10200095
TI  - [A new generation of female dental technicians].

PMID- 10200096
TI  - [At what point is the clientele satisfied?. Interview by Peter Jager].

PMID- 10200097
TI  - [The tooth-puller. Anonymous (after David Teniers le Jeune)].

PMID- 10200098
TI  - [Biomechanics and implants. The 1998 annual meeting of the Swiss Society for
      Implantology (SGI), Biomechanics and Implants, of 10 June 1998 in Davos].

PMID- 10200099
TI  - [New orthodontic treatment possibilities with Orthosystem implants. A report on
      the New Orthodontic Treatment Possibilities with Orthosystem Implants course in
      Bern of 16 October 1998].

PMID- 10200101
TI  - Proceedings of the Joint International Tropical Medicine Meeting. Bangkok,
      Thailand, 25-27 August 1997.

PMID- 10200100
TI  - [Procedural challenges in endodontics. Continuing education course (CEC) 6 May
      98].

PMID- 10200102
TI  - Trocars play a highly important role in the rapidly progressing field of
      laparoscopy.

PMID- 10200103
TI  - Endometriosis of the vermiform appendix (EVA) is an uncommon lesion with a
      frequency < 1% of all cases of pelvic endometriosis. Recent case.

PMID- 10200104
TI  - From the fibromyalgia challenge toward a new bio-psycho-social model of rheumatic
      diseases.

PMID- 10200105
TI  - Proceedings of the International Fibromyalgia Conference. Bad Nauheim, Germany,
      October 1997.

PMID- 10200106
TI  - Diabetes mellitus type 2, scientific approach to patient care models. 26th Annual
      congress of the Austrian Diabetes Society. Baden bei Wien, Austria, 19-21
      November 1998. Abstracts.

PMID- 10200107
TI  - Proceedings of the Vascular Smooth Muscle Symposium. Margretorp, Sweden, 21-25
      May 1998.

PMID- 10200108
TI  - Endovascular treatment of multiple aneurysms involving the posterior intracranial
      circulation.
AB  - The results of surgery on multiple intracranial aneurysms tha involve the
      vertebrobasilar circulation are poor, and associated patient mortality remains
      high. We describe the endovascular treatment of four patients with mutiple
      aneurysms that involved the posterior intracrancial circulation. Satisfactory
      occlusion of all aneurysms was achieved by using electrolytically detachable
      coils, and all patients had a good clinical recovery. Our early experience
      suggests that endovascular coil occlusion may be a particularly suitable method
      for treating this high-risk condition.

PMID- 10200109
TI  - New Frontiers in the Electrical Management of Cardiac Disorders. Proceedings of a
      symposium. Geneva, Switzerland, October 9-10, 1998.

PMID- 10200110
TI  - Infectivity of Marek's disease agent after different treatments used in vaccine
      production.

PMID- 10200111
TI  - Two-stage surgical hepatectomy and its effects on formation and metabolism of Cx
      reactive protein in the rabbit.

PMID- 10200113
TI  - Ameloblastic odontoma in the dog.

PMID- 10200112
TI  - Pharmacodynamics and treatment of mammals poisoned by Bufo marinus toxin.

PMID- 10200114
TI  - Immunodiffusion agar-gel test for demonstration of Borrelia anserina antigen
      produced by liver of infected chickens.

PMID- 10200115
TI  - Technique for the subcutaneous relocation of the common carotid artery in the
      horse.

PMID- 10200116
TI  - [How should a pruritic pityriasis rosea Gibert be treated?].

PMID- 10200117
TI  - [Could primary prevention or selective screening of melanoma be better targetted
      in general medicine? A prospective study to validate a self-assessed score].

PMID- 10200118
TI  - The fate of duplicated genes: loss or new function?
AB  - Gene duplication events are important sources of novel gene functions. However,
      more often than not, a duplicate gene may lose its function and become a
      pseudogene. What is the relative frequency of these two scenarios: functional
      divergence versus gene loss? Given that most non-neutral mutations are
      deleterious, gene loss should be far more frequent than divergence. However, a
      recent empirical study suggests that about 50% of all gene duplications will lead
      to functional divergence. The study infers the frequency of functional divergence
      from the size distribution of gene families produced by two successive genome
      duplications early in vertebrate evolution. Reasons for this unexpectedly high
      frequency of functional divergence are discussed.

PMID- 10200119
TI  - 1 + 1 = r4 and much much more.
AB  - Expression and mutational analysis has shown that the vertebrate Hox genes are
      instrumental in patterning of the developing embryo. However, the combined
      effects of functional redundancy, compensation, and synergy often obscure the
      precise roles of these genes. By combining gene targeting strategies with the
      analysis of regulatory sequences from the Hoxa1 and Hoff1 genes, it has been
      possible to bypass some of these complications and demonstrate their genetic and
      functional interactions during the development of the hindbrain and branchial
      arches.

PMID- 10200120
TI  - Antibiotic prophylaxis and treatment of cardiovascular disease.

PMID- 10200121
TI  - Estimation of risk reduction.

PMID- 10200122
TI  - Unexplained acronyms.

PMID- 10200123
TI  - Increased risk of myocardial infarction in men with both hypertriglyceridemia and
      elevated HDL cholesterol.

PMID- 10200124
TI  - Women versus men regarding outcome of CABG or PTCA.

PMID- 10200126
TI  - Flushing as a symptom of anaphylaxis.

PMID- 10200127
TI  - Detecting melanoma.

PMID- 10200128
TI  - Selective high dose gamma-globulin treatment in Kawasaki disease: assessment of
      clinical aspects and cost effectiveness.
AB  - BACKGROUND: High-dose intravenous gamma-globulin (IVGG) plus aspirin (ASA)
      treatment is effective in preventing coronary artery complications in acute
      Kawasaki disease (KD). However, gamma-globulin is very expensive, especially in
      Japan. Furthermore the indication for IVGG treatment and the optimal dose of
      gamma-globulin remain controversial. OBJECTIVES: To examine these two issues, we
      used Harada's scoring system to investigate whether a single 2 g/kg dose therapy
      has any advantage over the 5 day 400 mg/kg per day therapy. METHODS: We studied
      203 patients with KD who had no coronary artery complications on admission. Of
      these, 145 patients scored 4 or more on Harada score within the first 9 days of
      illness and were treated with IVGG treatment. Using a random number table, 72
      patients were selected to receive a single 2 g/kg dose (2 g group), while the
      remaining 73 patients were treated with 400 mg/kg per day for 5 consecutive days
      (400 mg group). Those who had a Harada score of three or less received no IVGG
      (non-IVGG group) treatment (58 patients). RESULTS: The incidence rate of coronary
      artery complications in the 2 g group was significantly lower than in the 400 mg
      group. The duration of high fever, positive duration of C-reactive protein and
      the number of hospital days in the 2 g group were each significantly shorter than
      in the 400 mg group. The total medical expense in the 2 g group was significantly
      lower than in the 400 mg group. There were no coronary artery complications in
      the non-IVGG group. CONCLUSIONS: It was found to be clinically more effective and
      more cost effective to select a patient by Harada's scoring system and, where a
      score of four or more was obtained, to administer a single 2 g/kg intravenous
      dose of gamma-globulin for acute KD.

PMID- 10200129
TI  - Changes in ventricular and muscle volumes of neonates.
AB  - BACKGROUND: To examine the changes in cardiac ventricular and muscle volumes in
      neonates, echocardiography was performed in 25 normal neonates at 3-5 and 30-35
      days after birth. METHODS: A standard apical four chamber view and a parasternal
      short axis view were used for the analysis of the left ventricle. For the
      analysis of the right ventricle, only an apical four-chamber view was used. A
      formula based on the area length method was used to calculate the left
      ventricular and muscle volumes and the single plane Simpson's rule was used for
      the right ventricular and muscle volumes. RESULTS: The left ventricular and
      muscle volumes per body surface did not change during the month following birth.
      The ratio of the muscle to ventricular volume of the left ventricle was also
      unchanged. However, the ratios of the right muscle volume to body surface and to
      the ventricular volume decreased after one month. CONCLUSIONS: The authors
      suggest that the decreases in pulmonary hypertension and right ventricular stroke
      volume play a role in the changes of right muscle volume.

PMID- 10200130
TI  - Cardiovascular function before and after iron therapy by echocardiography in
      patients with iron deficiency anemia.
AB  - BACKGROUND: The aim of the study was to estimate the left ventricular
      contractility using the ratio of left ventricular end-systolic wall stress to
      left ventricular end-systolic volume index in patients with iron deficiency
      anemia, for which there are no previous reports. METHODS: Cardiovascular
      functions were evaluated using echocardiography and pulsed Doppler
      echocardiography in 30 children aged 3-14 years (hemoglobin 4.9-8.5 g/dL),
      before, during and after iron therapy. We also studied 38 healthy children as a
      control group. RESULTS: The left ventricular preload was significantly higher and
      the left ventricular afterload was lower in the patients with anemia before iron
      therapy. The ratio of left ventricular end-systolic wall stress to left
      ventricular volume, an index of systolic function that is independent of preload
      and afterload, was significantly lower in the patients with anemia before iron
      therapy (before iron therapy 2.13 +/- 0.44, after therapy 3.52 +/- 0.76, healthy
      controls 3.42 +/- 0.70). Left ventricular early diastolic filling was
      significantly higher in the patients with anemia before iron therapy. The cardiac
      index was also significantly higher before therapy because of the increases in
      preload, heart rate and early diastolic filling, as well as the decrease of
      afterload. There were no significant differences in the indices of cardiovascular
      function between anemic patients after iron therapy compared with control
      subjects. CONCLUSIONS: The ratio of left ventricular end-systolic wall stress to
      the left ventricular volume index and the cardiac index suggested that a
      hemoglobin concentration < or = 6 g/dL was associated with left ventricular
      dysfunction and circulatory congestion.

PMID- 10200131
TI  - Microstructure of longitudinal 24 hour electroencephalograms in healthy preterm
      infants.
AB  - BACKGROUND: The aims of the present study were to find electroencephalographic
      parameters that appropriately represent the microstructure of
      electroencephalograms (EEG) in different sleep states and to find quantitative
      criteria for an automatic system of sleep-state classification in preterm
      infants. METHODS AND RESULTS: Continuous 24 h EEG was performed in 14 normal
      preterm infants for whom 26 EEG records were obtained. Based on respiratory
      activity, body movements and rapid eye movements, the different sleep states were
      determined visually in 30 s epochs. Seven EEG parameters, Minimum Akaike
      Information Criterion (Min-AIC), total power (TP), component powers (delta,
      theta, alpha and beta), and the discontinuity were calculated by means of
      autoregressive and component analyses in 30 s epochs. The student's t test was
      performed independently for each parameter. Four of the seven parameters (Min
      AIC, TP, delta component power and the discontinuity) showed significant
      differences in different sleep states. The results of multivariate discriminant
      analysis revealed that the combination of Min-AIC, TP, delta component power and
      the discontinuity of EEG defined the EEG sleep states well. CONCLUSION: The
      combination of Min-AIC. TP, delta component power and the discontinuity of EEG
      defined the EEG sleep states well and might be used to predict sleep state
      changes in preterm infants of conceptional ages of more than 30 weeks.

PMID- 10200132
TI  - Cardiac side effects of long-acting beta-2 agonist salmeterol in asthmatic
      children.
AB  - BACKGROUND: Salmeterol is a new long-acting beta 2 selective adrenoreceptor
      agonist. There are some reports about the cardiac side-effects of salmeterol in
      asthmatic adults. The aim of this study was to determine the cardiac side effects
      of salmeterol in children. METHODS: Seventeen children with moderate asthma (aged
      between 6 and 13 years, mean 8.76 years) received salmeterol with a spacer device
      (Volumatic 200 micrograms daily, b.i.d.) for 3 weeks. All the children were
      evaluated by 24 h ambulatory electrocardiography monitoring and echocardiography
      before, on the second and on the 21st day of treatment. RESULTS: In minimum heart
      rate measurements, there were significant differences between the baseline (mean
      +/- SD 54.29 +/- 7.13), second (59.24 +/- 6.86) and 21st day (60.65 +/- 8.23)
      results. Also, the mean heart rate before the treatment (89.59 +/- 6.78) was
      significantly different from that on the second (94.76 +/- 6.51) and 21st day
      (92.65 +/- 8.90) of treatment. Although all the values were within normal limits
      and there were no significant differences between the control group's values, a
      trend of increase in mean and the minimum heart rates was seen. There were no
      significant differences in blood pressure, serum K+, maximum heart rate,
      supraventricular and ventricular ectopic beats, ejection fraction, stroke volume,
      cardiac output and corrected QT interval at any time. No complaints of tremors or
      palpitations were reported. CONCLUSIONS: As no cardiac side effects were
      detected, it could be concluded that salmeterol is quite a safe drug for use in
      childhood asthma treatment.

PMID- 10200133
TI  - Expression of interleukin-2 receptor, CD25, on CD4 lymphocytes in response to
      varicella-zoster virus antigen among patients with malignancies immunized with
      live attenuated varicella vaccine.
AB  - BACKGROUND: Varicella in an immunocompromised host is often serious or life
      threatening. A live attenuated varicella vaccine was developed in Japan. It has
      been reported that the varicella vaccine is safe and highly protective against
      severe varicella in children with leukemia and other malignancies. It is
      important to investigate the persistence of varicella-zoster virus (VZV)-specific
      cell-mediated immunity in patients with malignancies who have been immunized with
      varicella vaccine. METHODS: Sixteen patients with malignancies and 11 controls
      had been immunized with attenuated live varicella vaccine. The duration from
      vaccination to the study ranged from 2 to 16 years (mean 10 years). Nineteen
      patients and 20 controls had experienced natural varicella infection. Peripheral
      blood mononuclear cells (PBMC) from patients and controls were cultured with VZV
      antigen for 6 days and the percentage of cluster of differentiation antigen
      (CD)25 among CD4 lymphocytes was calculated by flow cytometry. CONTROLS: The
      percentage of CD25-positive cells among CD4 lymphocytes significantly increased
      in response to the VZV antigen in vaccinated patients and patients with past
      natural varicella infection as observed in the controls. CONCLUSIONS: These data
      show that VZV-specific cell-mediated immunity is induced and persists in patients
      with malignancies after immunization with live varicella vaccine.

PMID- 10200134
TI  - Heterogeneity in F-actin polymerization of cord blood polymorphonuclear
      leukocytes stimulated by N-formyl-methionyl-leucyl-phenylalanine.
AB  - BACKGROUND: To elucidate the mechanism responsible for defects of
      polymorphonuclear leukocyte (PMNL) chemotaxis of neonates, we determined actin
      polymerization of NBD (7-nitrobenz-2-oxa-diazol)-phallacidin-stained PMNL
      following stimulation with either N-formyl-methionyl-leucyl-phenylalanine (fMLP)
      or phorbol myristate acetate (PMA) in cord blood and adult controls. METHODS: We
      measured F-actin content in PMNL stained with NBD-phallacidin using flow
      cytometry. RESULTS: Relative F-actin polymerization, that is, a ratio of
      stimulated F-actin to basal F-actin, was significantly decreased in cord blood
      PMNL when compared with that of adult PMNL. Distribution of fMLP-stimulated F
      actin showed a bimodal pattern, while adult PMNL disclosed a single pattern.
      Following stimulation with PMA, however, F-actin levels were equal in both cord
      and adult PMNL. A fluorescein isothiocyanate-conjugated fMLP receptor assay
      showed no significant difference in binding capacity of fMLP receptors between
      adult and cord PMNL. CONCLUSION: These results indicate that a deficiency of PMNL
      chemotaxis in neonates may be due, in part, to decreased relative F-actin
      polymerization, which may be caused by functional heterogeneity in cord blood
      PMNL.

PMID- 10200135
TI  - Evaluation of the pancreas reserve in siblings of type I diabetic children.
AB  - INTRODUCTION: The purpose of this study was to determine the pancreas reserve in
      siblings of diabetic patients by screening islet cell antibodies (ICA), insulin
      auto antibodies (IAA), reduced C-peptide levels, first-phase insulin release and
      the derangement of cellular immunity (reduction of natural killer cells,
      abnormality of the T cell subpopulations). METHODS AND RESULTS: Twelve siblings
      (aged 9.3 +/- 2.8 years) of diabetic children were evaluated and results were
      compared with the control group (12.1 +/- 3.5 years). For siblings of the
      diabetic children, fasting, post-prandial and glucagon response C-peptide mean
      values were 2.2 +/- 1.2, 7.2 +/- 7.1 and 5.3 +/- 3.6 ng/mL, respectively, while
      in the control group they were 1.5 +/- 0.8, 3.6 +/- 2.0 and 5.1 +/- 2.9 ng/mL,
      respectively. There were no differences between the two groups. In 33%,
      postprandial C-peptide, and in 11% of the siblings, glucagon response C-peptide
      values were exaggerated. In siblings the first phase insulin release (FPIR)
      during an intravenous glucose tolerance test was 128.5 +/- 96.6 (above the 50th
      percentile) and stimulated insulin release (SIR) was 103.8 +/- 92.5 (above 25th
      percentile). Sibling values were significantly lower than the control group (FPIR
      152.4 +/- 42.5, P = 0.01; SIR 134.9 +/- 38.2, P = 0.01). Values for FPIR (in two
      children) and SIR (three cases) were below the 5th percentile. In one, FPIR and
      SIR levels were both below the 1st percentile. Islet cell antibodies and IAA were
      also present in this subject. Treatment with nicotinamide was started in the
      cases with FPIR and SIR below the 5th percentile. We did not observe overt
      diabetic symptoms during the follow-up period of more than 3 years. CONCLUSION:
      We recommend that borderline insulin secretion be tested annually in siblings who
      show insufficient FPIR.

PMID- 10200136
TI  - Prevalence of specific allergic diseases in school children as related to
      parental atopy.
AB  - BACKGROUND: Our objective was to investigate the influence of parental allergy on
      the manifestations and course of allergic disease in children. METHODS AND
      RESULTS: A total of 15,234 school children aged 6 and 9 years were evaluated by
      means of questionnaires completed by their parents in a cross-sectional survey
      conducted in Tokushima, Japan. The prevalence and relative risk ratio (RRR) for
      parental allergy in children with atopic dermatitis, asthma and allergic rhinitis
      were 6.4% (RRR 2.5), 3.2% (RRR 2.4) and 15% (RRR 2.4), respectively. The risk of
      atopic dermatitis was particularly high in children whose parent had atopic
      dermatitis, with an RRR of 2.8 (father) and 3.7 (mother). Children with a
      parental history of asthma also had a high risk of that disorder (RRR of father
      5.3, mother 6.2). However, the risk of allergic rhinitis was no different in
      children with a parental history of allergic rhinitis or from children with a
      parental history of asthma and atopic dermatitis. A history of allergic disease
      in both parents, especially of asthma and atopic dermatitis, increased the risk
      of allergic disease in the child. Milder symptoms, such as wheezy bronchitis, in
      schoolchildren were similarly related with the same hereditary tendency as the
      identical allergic disease. The disappearance of allergic symptoms with age also
      related to a hereditary component, being less likely in children with a history
      of parental allergy than in those without such an atopic history. CONCLUSIONS:
      The manifestations and course of allergic disease in school children relate to
      parental allergic disease.

PMID- 10200137
TI  - Influence of valproic acid on the expression of various acyl-CoA dehydrogenases
      in rats.
AB  - BACKGROUND: Valproic acid (2-propyl-N-pentanoic acid, VPA) causes severe hepatic
      dysfunction, similar to Reye's syndrome, in a small number of patients. An
      enhanced excretion of dicarboxylic acids by patients indicates an interference
      with mitochondrial beta-oxidation. We investigated the expression of various acyl
      coenzyme A (acyl-CoA) dehydrogenases (ACD), which catalyze the first step of beta
      oxidation in VPA-treated rats. METHODS: The control group received normal saline
      and the experimental group received VPA (500 mg/kg per day) by intraperitoneal
      injections for 7 days. Various clinical chemistry parameters in rat blood and
      free and total carnitine levels in plasma and tissue were determined.
      Mitochondria were isolated from rat liver and heart and the relative amount of
      each ACD protein was determined by immunoblot analysis. Total RNA was prepared
      from various tissues and the mRNA levels for various ACD were measured by slot
      blot hybridization analysis using respective cDNA probes. RESULTS: Administration
      of VPA to rats caused various metabolic effects including hypoglycemia,
      hyperammonemia and decreased beta-hydroxybutyrate concentration. Free carnitine
      levels in plasma and heart were also decreased. Enzyme activities of various acyl
      CoA dehydrogenases, which are involved in fatty acid oxidation, decreased
      moderately in heart (57-79%), and slightly in liver (78-95%). The most prominent
      effects were observed in mRNA levels involved in fatty acid oxidation (short-,
      medium- and long-chain acyl-CoA dehydrogenase). Each mRNA increased in the liver,
      kidney, skeletal muscle and heart to varying degrees when rats were fed ad
      libitum. The increase of short- and medium- chain acyl-CoA dehydrogenase mRNA in
      the heart were particularly large. However, 3 day starvation strongly inhibited
      expression of ACD in VPA-treated rats. There was an apparent decrease in the
      amount of ACD mRNA and proteins in VPA-treated liver. CONCLUSIONS: Valproic acid
      causes enhanced expression of fatty ACD mRNA, especially in the heart, by a
      feedback mechanism related to inhibition of beta-oxidation in rats fed ad
      libitum. However, it impairs the expression of ACD in the liver when there is a
      drastic change in nutritional state.

PMID- 10200138
TI  - Serum prolactin in neonatal seizures.
AB  - BACKGROUND: Prolactin is the most specific neurohormone that is elevated after
      seizures. This study was undertaken to determine the clinical usefulness of
      plasma prolactin as a diagnostic aid in differential diagnosis of neonatal
      convulsions. METHODS: Forty-five patients followed for seizures were included in
      the study. Postictal serum prolactin levels were obtained 30 min after the onset
      of the seizures. A second sample obtained 24 h later was used to measure an
      unstimulated serum prolactin level. RESULTS: The most common cause of seizure was
      hypoxic ischemic encephalopathy (HIE) followed by sepsis. In patients with HIE,
      postictal serum prolactin levels were significantly higher than the unstimulated
      levels (P < 0.0002). Additionally, postictal prolactin levels were significantly
      higher than the unstimulated levels in clonic (P < 0.02) and tonic convulsions (P
      < 0.001). CONCLUSIONS: We conclude that the postictal serum prolactin level may
      be a marker in the differentiation of seizures as well as providing important
      information about their etiology. Further studies are needed to assess the normal
      range of serum prolactin levels in unstressed newborns.

PMID- 10200139
TI  - Lipoprotein A profiles in Arab newborns.
AB  - BACKGROUND: Lipoprotein A (LpA) is an intriguing lipoprotein with unquestionable
      genetic determination which is expressed early in life. The increasing interest
      in LpA is due to its established recognition as an important independent risk
      factor for premature atherosclerosis in cardiovascular diseases. Coronary heart
      disease is a major cause of morbidity and premature mortality in Kuwait. The
      present study was designed to measure serum LpA concentrations in Arab newborns
      to establish reference values for LpA in newborns and its relationship to factors
      present in the mother and baby. METHODS: Serum LpA concentration was analyzed in
      the cord blood of 107 Arab newborns by an enzyme-linked immunosorbent assay.
      RESULTS: The mean and median LpA were 54.8 mg/L and 33 mg/L, respectively (range
      1-500 mg/L). The frequency distribution of LpA in cord blood was skewed to the
      right, with the highest frequencies of LpA below 100 mg/L. Mean LpA levels were
      significantly higher in female infants compared with male infants at birth (77.27
      +/- 108.12 mg/L vs 40.2 +/- 41.43 mg/L, P < 0.05). Lipoprotein A concentrations
      in newborns were not influenced by material characteristics or type of delivery.
      Moreover, neonatal LpA concentration did not correlate with birthweight (BW) or
      body mass index (BMI). CONCLUSIONS: Lipoprotein A concentration at birth is low
      and is not related to maternal characteristics. Additionally, the development of
      circulating LpA in serum at birth was independent of BW and BMI.

PMID- 10200140
TI  - Estimated nutritional intake based on the reference growth curves for extremely
      low birthweight infants.
AB  - BACKGROUND: Although the optimal goal of extremely low birthweight (ELBW) infants
      has been debated, it can be argued that the best nutritional strategy for ELBW
      infants is one which achieves better growth while preventing neurological
      sequelae due to nutritional inadequacy, even if it does not mimic fetal growth.
      Our aim is to propose an advisable and practically feasible nutritional intake
      for ELBW infants. METHODS: We retrospectively investigated the nutritional intake
      in 16 ELBW infants (gestational age 26.7 weeks, birthweight 879.6 g), who
      exceeded the standard growth curves for Japanese infants of ELBW. We also
      analyzed the nutritional composition of human milk from 15 mothers delivering
      before term (PT milk) until the 12th week of lactation. The nutritional intake
      was calculated according to the composition of the parenteral and enteral
      regimen. RESULTS: The infants tolerated more than 100 mL/kg per day of milk until
      the fourth week of life. An average weight gain of more than 15 g/kg per day was
      achieved by the sixth week. An advisable nutritional intake capable of sustaining
      ELBW infants in a stable growing phase was calculated as the sum of the mean plus
      1SD of the daily nutritional intake. CONCLUSIONS: To exceed the ordinary growth
      curves for ELBW Japanese infants, it was suggested that more than 100 mL milk/kg
      per day could be fed until the fourth week of life, while the advisable daily
      intake of nutrients after six weeks of life should be as follows: water 160
      mL/kg, protein 3.2 g/kg, fat 7.4 g/kg, carbohydrate 12.8 g/kg, energy 544 kJ/kg,
      the following minerals in mg/kg: sodium 45, chloride 82, potassium 110, calcium
      140, phosphorus 70, magnesium 11, zinc 0.5 and copper at 60 micrograms/kg.
      Further studies will be needed to confirm the safety and effectiveness of this
      advisable intake for ELBW infants.

PMID- 10200141
TI  - Interleukin 8 in the tracheobronchial aspirate of infants acts as a neutrophil
      chemotactic factor in the development of chronic lung disease.
AB  - BACKGROUND: We have already reported that there are some periods when a high
      interleukin 8 (IL-8) concentration is observed in the tracheobronchial aspirate
      of infants with chronic lung disease (CLD), although the changing pattern of the
      IL-8 concentration varies depending on the type of CLD. Interleukin 8 is known as
      a neutrophil chemotactic agent. Therefore, we asked whether IL-8 is an important
      neutrophil chemotactic factor in the tracheobronchial aspirate of infants who
      later develop CLD. METHODS AND RESULTS: We measured the neutrophil chemotactic
      activity of the tracheobronchial aspirate in CLD infants with or without anti-IL
      8 antibody. Preincubation with anti-IL-8 immunoglobulinG resulted in a
      significant reduction of neutrophil chemotactic activity in the tracheobronchial
      aspirate. In infants with CLD following respiratory distress syndrome, there was
      a significant relationship between the IL-8 concentration and the neutrophil
      chemotactic activity of tracheobronchial aspirate without anti-IL-8 antibody,
      although no significant relationship was seen in infants with CLD following intra
      uterine infection or with other CLD. CONCLUSIONS: Interleukin 8 in the
      tracheobronchial aspirate seems to play a significant role in recruiting
      neutrophils into the airways of patients with CLD, especially CLD following
      respiratory distress syndrome. We believe that in this type of CLD, IL-8 in the
      lung is generated as a result of hyperoxia rather than infection. In this
      situation, production of other neutrophil chemotactic factors or some factors
      that inhibit IL-8 activity may be insignificant.

PMID- 10200142
TI  - Prenatal and postnatal histories of very low birthweight infants who developed
      hepatoblastoma.
AB  - BACKGROUND: Hepatoblastoma in children of very low birthweight (< 1500 g) is
      increasing in Japan and this has suggested the presence of either a genetic or
      environmental etiology. This study was aimed at revealing common prenatal and
      postnatal histories, including family history of hepatoblastomas in children of
      very low birthweight. METHODS AND RESULTS: The medical records of 15 patients,
      nine boys and six girls, were reviewed. The patients were diagnosed at the age of
      6-77 months (median 16 months). Their birthweight ranged from 560 to 1380 g
      (median 826 g) and the gestational age was 23-33 weeks (median 25 weeks). No
      parents were exposed to any occupational risk factors and there were no
      characteristic features in the parents' history or the maternal reproductive
      history, although one patient was born to a mother who had taken a contraceptive
      before she got pregnant with the patient as a result of in vitro fertilization. A
      ventricular septal defect and an atresia of the external auditory canal were
      congenital anomalies seen in the patients, but congenital anomalies associated
      with hepatoblastoma were not seen. Early postnatal illnesses included respiratory
      distress syndrome in six patients, symptomatic patent ductus arteriosus in three
      patients, chronic lung disease in seven patients, cytomegalovirus hepatitis in
      one patient and cholelithiasis in one patient. Oxygen therapy was given to 13
      patients for a period of 4-508 days (median 112 days) and lengths of oxygen
      therapy and assisted ventilation were significantly longer in patients with a
      stage IIIB or IV tumor than those with a stage II or IIIA tumor (P = 0.0040 and
      0.0190, respectively). Furosemide was used in 13 patients for a period of 6-460
      days (median 88 days) and the length of the treatment was also significantly
      longer in patients with advanced tumors (P = 0.0420). Among the patients at 23-25
      weeks of gestation, these treatments tended to be longer in patients with a stage
      IIIB or IV tumor than those with a stage II or IIIA tumor. CONCLUSIONS: These
      results suggest the presence of an environmental etiology, rather than a genetic
      one, which is responsible for the development of hepatoblastoma in children of
      very low birthweight. Close monitoring of the children after being discharged
      from the neonatal intensive care unit is essential and a case-control study is
      necessary to identify risk factors for hepatoblastoma in children of very low
      birthweight.

PMID- 10200143
TI  - Atrioventricular block in a patient with growth hormone deficiency during growth
      hormone therapy.

PMID- 10200144
TI  - Isoproterenol continuous inhalation therapy in an infant with severe
      bronchiolitis lifesaving therapy.

PMID- 10200145
TI  - Continuous subcutaneous insulin injection for a case of mitochondrial cytopathy
      with diabetes mellitus requiring a large amount of insulin.

PMID- 10200146
TI  - A case of group A beta-hemolytic streptococcal proctitis prior to pharyngitis.

PMID- 10200147
TI  - Treatment of refractory Evans' syndrome with cyclosporine and prednisone.

PMID- 10200148
TI  - Peculiar odor of traditional food and maple syrup urine disease.

PMID- 10200149
TI  - A young infant with Goldbloom syndrome.

PMID- 10200150
TI  - Thrombocytopenia caused by acquired cytomegalovirus infection in children.

PMID- 10200151
TI  - Guideline for weaning (revised edition). Ministry of Health and Welfare, Japan.

PMID- 10200152
TI  - A versatile mismatch recognition agent: specific cleavage of a plasmid DNA at a
      single base mispair.
AB  - [Rh(bpy)2(chrysi)]3+ is a novel, sterically bulky DNA intercalator that has been
      designed to bind specifically in the destabilized regions near DNA base
      mismatches and, upon photoactivation, to cleave the DNA backbone. Here the
      molecule is shown to be both a general and remarkably specific mismatch
      recognition agent. Specific DNA cleavage is observed at over 80% of mismatch
      sites in all the possible single base pair sequence contexts around the mispaired
      bases. Moreover, the complex is highly site-specific; it is shown to recognize
      and photocleave at a single base mismatch in a 2725 base pair linearized plasmid
      heteroduplex. Sterically demanding intercalators such as [Rh(bpy)2(chrysi)]3+ may
      have application both in mutation detection systems and as mismatch-specific
      chemotherapeutic agents.

PMID- 10200153
TI  - Efficient formation of nitric oxide from selective oxidation of N-aryl N'
      hydroxyguanidines by inducible nitric oxide synthase.
AB  - Inducible nitric oxide synthase (NOS II) efficiently catalyzes the oxidation of N
      (4-chlorophenyl)N'-hydroxyguanidine 1 by NADPH and O2, with concomitant formation
      of the corresponding urea and NO. The characteristics of this reaction are very
      similar to those of the NOS-dependent oxidation of endogenous Nomega-hydroxy-L
      arginine (NOHA), i.e., (i) the formation of products resulting from an oxidation
      of the substrate C=N(OH) bond, the corresponding urea and NO, in a 1:1 molar
      ratio, (ii) the absolute requirement of the tetrahydrobiopterin (BH4) cofactor
      for NO formation, and (iii) the strong inhibitory effects of L-arginine (L-arg)
      and classical inhibitors of NOSs. N-Hydroxyguanidine 1 is not as good a substrate
      for NOS II as is NOHA (Km = 500 microM versus 15 microM for NOHA). However, it
      leads to relatively high rates of NO formation which are only 4-fold lower than
      those obtained with NOHA (Vm = 390 +/- 50 nmol NO min-1 mg protein-1,
      corresponding roughly to 100 turnovers min-1). Preliminary results indicate that
      some other N-aryl N'-hydroxyguanidines exhibit a similar behavior. These results
      show for the first time that simple exogenous compounds may act as NO donors
      after oxidative activation by NOSs. They also suggest a possible implication of
      NOSs in the oxidative metabolism of certain classes of xenobiotics.

PMID- 10200154
TI  - Structural and dynamical properties of a partially unfolded Fe4S4 protein: role
      of the cofactor in protein folding.
AB  - Heteronuclear multidimensional NMR spectroscopy was used to investigate in detail
      the structural and dynamical properties of a partially unfolded intermediate of
      the reduced high-potential iron-sulfur protein (HiPIP) from Chromatium vinosum
      present in 4 M guanidinium chloride solution. After an extensive assignment of
      15N and 1H resonances, NOE data, proton longitudinal relaxation times, and
      3JHNHalpha coupling constants as well as 15N relaxation parameters (T1, T2,
      T1rho, and 1H-15N NOE) were obtained and used to build a structural model of the
      intermediate. The Fe4S4 cluster of the HiPIP plays a decisive role in determining
      the resulting structure, which is random in the N-terminal half of the protein
      and partially organized in the loops between the cysteines bound to the cluster.
      Consistent with the structural data, the backbone mobility is typical of folded
      proteins in the regions where there are elements of structure and increases with
      the structural indetermination.

PMID- 10200155
TI  - A refined model for the solution structure of oxidized putidaredoxin.
AB  - A refined model for the solution structure of oxidized putidaredoxin (Pdxo), a
      Cys4Fe2S2 ferredoxin, has been determined. A previous structure (Pochapsky et al.
      (1994) Biochemistry 33, 6424-6432; PDB entry ) was calculated using the results
      of homonuclear two-dimensional NMR experiments. New data has made it possible to
      calculate a refinement of the original Pdxo solution structure. First,
      essentially complete assignments for diamagnetic 15N and 13C resonances of Pdxo
      have been made using multidimensional NMR methods, and 15N- and 13C-resolved
      NOESY experiments have permitted the identification of many new NOE restraints
      for structural calculations. Stereospecific assignments for leucine and valine
      CH3 resonances were made using biosynthetically directed fractional 13C labeling,
      improving the precision of NOE restraints involving these residues. Backbone
      dihedral angle restraints have been obtained using a combination of two
      dimensional J-modulated 15N,1H HSQC and 3D (HN)CO(CO)NH experiments. Second, the
      solution structure of a diamagnetic form of Pdx, that of the C85S variant of
      gallium putidaredoxin, in which a nonligand Cys is replaced by Ser, has been
      determined (Pochapsky et al. (1998) J. Biomol. NMR 12, 407-415), providing
      information concerning structural features not observable in the native
      ferredoxin due to paramagnetism. Third, a crystal structure of a closely related
      ferredoxin, bovine adrenodoxin, has been published (Muller et al. (1998)
      Structure 6, 269-280). This structure has been used to model the metal binding
      site structure in Pdx. A family of fourteen structures is presented that exhibits
      an rmsd of 0.51 A for backbone heavy atoms and 0.83 A for all heavy atoms.
      Exclusion of the modeled metal binding loop region reduces overall the rmsd to
      0.30 A for backbone atoms and 0.71 A for all heavy atoms.

PMID- 10200156
TI  - Characteristics and crystal structure of bacterial inosine-5'-monophosphate
      dehydrogenase.
AB  - IMP dehydrogenase (IMPDH) is an essential enzyme that catalyzes the first step
      unique to GTP synthesis. To provide a basis for the evaluation of IMPDH
      inhibitors as antimicrobial agents, we have expressed and characterized IMPDH
      from the pathogenic bacterium Streptococcus pyogenes. Our results show that the
      biochemical and kinetic characteristics of S. pyogenes IMPDH are similar to other
      bacterial IMPDH enzymes. However, the lack of sensitivity to mycophenolic acid
      and the Km for NAD (1180 microM) exemplify some of the differences between the
      bacterial and mammalian IMPDH enzymes, making it an attractive target for
      antimicrobial agents. To evaluate the basis for these differences, we determined
      the crystal structure of the bacterial enzyme at 1.9 A with substrate bound in
      the catalytic site. The structure was determined using selenomethionine
      substituted protein and multiwavelength anomalous (MAD) analysis of data obtained
      with synchrotron radiation from the undulator beamline (19ID) of the Structural
      Biology Center at Argonne's Advanced Photon Source. S. pyogenes IMPDH is a
      tetramer with its four subunits related by a crystallographic 4-fold axis. The
      protein is composed of two domains: a TIM barrel domain that embodies the
      catalytic framework and a cystathione beta-synthase (CBS) dimer domain of so far
      unknown function. Using information provided by sequence alignments and the
      crystal structure, we prepared several site-specific mutants to examine the role
      of various active site regions in catalysis. These variants implicate the active
      site flap as an essential catalytic element and indicate there are significant
      differences in the catalytic environment of bacterial and mammalian IMPDH
      enzymes. Comparison of the structure of bacterial IMPDH with the known partial
      structures from eukaryotic organisms will provide an explanation of their
      distinct properties and contribute to the design of specific bacterial IMPDH
      inhibitors.

PMID- 10200157
TI  - Nucleophilic activation by positioning in phosphoryl transfer catalyzed by
      nucleoside diphosphate kinase.
AB  - The nonenzymatic reaction of ATP with a nucleophile to generate ADP and a
      phosphorylated product proceeds via a dissociative transition state with little
      bond formation to the nucleophile. Consideration of the dissociative nature of
      the nonenzymatic transition state leads to the following question: To what extent
      can the nucleophile be activated in enzymatic phosphoryl transfer? We have
      addressed this question for the NDP kinase reaction. A mutant form of the enzyme
      lacking the nucleophilic histidine (H122G) can be chemically rescued for ATP
      attack by imidazole or other exogenous small nucleophiles. The ATP reaction is 50
      fold faster with the wild-type enzyme, which has an imidazole nucleophile
      positioned for reaction by a covalent bond, than with H122G, which employs a
      noncovalently bound imidazole nucleophile [(kcat/KM)ATP]. Further, a 4-fold
      advantage for imidazole positioned in the nucleophile binding pocket created by
      the mutation is suggested from comparison of the reaction of H122G and ATP with
      an imidazole versus a water nucleophile, after correction for the intrinsic
      reactivities of imidazole and water toward ATP in solution. X-ray structural
      analysis shows no detectable rearrangement of the residues surrounding His 122
      upon mutation to Gly 122. The overall rate effect of approximately 10(2)-fold for
      the covalent imidazole nucleophile relative to water is therefore attributed to
      positioning of the nucleophile with respect to the reactive phosphoryl group.
      This is underscored by the more deleterious effect of replacing ATP with
      AlphaTauPgammaS in the wild-type reaction than in the imidazole-rescued mutant
      reaction, as follows. For the wild-type, AlphaTauPgammaS presumably disrupts
      positioning between nucleophile and substrate, resulting in a large thio effect
      of 300-fold, whereas precise alignment is already disrupted in the mutant because
      there is no covalent bond to the nucleophile, resulting in a smaller thio effect
      of 10-fold. In summary, the results suggest a catalytic role for activation of
      the nucleophile by positioning in phosphoryl transfer catalyzed by NDP kinase.

PMID- 10200158
TI  - Structural basis for the design of antibiotics targeting peptide deformylase.
AB  - While protein synthesis in bacteria begins with a formylated methionine, the
      formyl group of the nascent polypeptide is removed by peptide deformylase. Since
      eukaryotic protein synthesis does not involve formylation and deformylation at
      the N-terminus, there has been increasing interest in peptide deformylase as a
      potential target for antibacterial chemotherapy. Toward this end and to aid in
      the design of effective antibiotics targeting peptide deformylase, the structures
      of the protein-inhibitor complexes of both the cobalt and the zinc containing
      Escherichia coli peptide deformylase bound to the transition-state analogue, (S)
      2-O-(H-phosphonoxy)-L-caproyl-L-leucyl-p-nitroanilide (PCLNA), have been
      determined. The proteins for both deformylase-inhibitor complexes show basically
      the same fold as for the native enzyme. The PCLNA inhibitor adopts an extended
      conformation and fits nicely into a hydrophobic cavity located near the metal
      site. On the basis of these structures, guidelines for the design of high
      affinity deformylase inhibitors are suggested. As our results show that the
      protein residues which interact with the PCLNA inhibitor are conserved over a
      wide variety of species, we suggest that antibiotics targeting deformylase could
      have wide applicability.

PMID- 10200160
TI  - alpha-lytic protease precursor: characterization of a structured folding
      intermediate.
AB  - The bacterial alpha-lytic protease (alphaLP) is synthesized as a precursor
      containing a large N-terminal pro region (Pro) transiently required for correct
      folding of the protease [Silen, J. L., and Agard, D. A. (1989) Nature 341, 462
      464]. Upon folding, the precursor is autocatalyticly cleaved to yield a tight
      binding inhibitory complex of the pro region and the fully folded protease
      (Pro/alphaLP). An in vitro purification and refolding protocol has been developed
      for production of the disulfide-bonded precursor. A combination of spectroscopic
      approaches have been used to compare the structure and stability of the precursor
      with either the Pro/alphaLP complex or isolated Pro. The precursor and complex
      have significant similarities in secondary structure but some differences in
      tertiary structure, as well as a dramatic difference in stability. Correlations
      with isolated Pro suggest that the pro region part of the precursor is fully
      folded and acts to stabilize and structure the alphaLP region. Precursor folding
      is shown to be biphasic with the fast phase matching the rate of pro region
      folding. Further, the rate-limiting step in oxidative folding is formation of the
      disulfide bonds and autocatalytic processing occurs rapidly thereafter. These
      studies suggests a model in which the pro region folds first and catalyzes
      folding of the protease domain, forming the active site and finally causing
      autocatalytic cleavage of the bond separating pro region and protease. This last
      processing step is critical as it allows the protease N-terminus to rearrange,
      providing the majority of net stabilization of the product Pro/alphaLP complex.

PMID- 10200159
TI  - Peptidomimetic probes and molecular modeling suggest that Alzheimer's gamma
      secretase is an intramembrane-cleaving aspartyl protease.
AB  - The amyloid beta-protein (Abeta), implicated in the pathogenesis of Alzheimer's
      disease (AD), is a proteolytic metabolite generated by the sequential action of
      beta- and gamma-secretases on the amyloid precursor protein (APP). The two main
      forms of Abeta are 40- and 42-amino acid C-terminal variants, Abeta40 and
      Abeta42. We recently described a difluoro ketone peptidomimetic (1) that blocks
      Abeta production at the gamma-secretase level [Wolfe, M. S., et al. (1998) J.
      Med. Chem. 41, 6-9]. Although designed to inhibit Abeta42 production, 1 also
      effectively blocked Abeta40 formation. Various amino acid changes in 1 still
      resulted in inhibition of Abeta40 and Abeta42 production, suggesting relatively
      loose sequence specificity by gamma-secretase. The alcohol counterparts of
      selected difluoro ketones also lowered Abeta levels, indicating that the ketone
      carbonyl is not essential for activity and suggesting that these compounds
      inhibit an aspartyl protease. Selected compounds inhibited the aspartyl protease
      cathepsin D but not the cysteine protease calpain, corroborating previous
      suggestions that gamma-secretase is an aspartyl protease with some properties
      similar to those of cathepsin D. Also, since the gamma-secretase cleavage sites
      on APP are within the transmembrane region, we consider the hypothesis that this
      region binds to gamma-secretase as an alpha-helix and discuss the implications of
      this model for the mechanism of certain forms of hereditary AD.

PMID- 10200161
TI  - The folding and structural integrity of the first LIN-12 module of human Notch1
      are calcium-dependent.
AB  - Notch1 is a member of a conserved family of large modular type 1 transmembrane
      receptors that control differentiation in multicellular animals. Notch function
      is mediated through a novel signal transduction pathway involving successive
      ligand-induced proteolytic cleavages that serve to release the intracellular
      domain of Notch, which then translocates to the nucleus and activates downstream
      transcription factors. The extracellular domain of all Notch receptors have three
      iterated LIN-12 modules that appear to act as negative regulatory domains,
      possibly by limiting proteolysis. Each LIN-12 module contains three disulfide
      bonds and three conserved aspartate (D) or asparagine (N) residues. To begin to
      understand the structural basis for LIN-12 function, the first LIN-12 module of
      human Notch1 (rLIN-12.1) has been expressed recombinantly in Escherichia coli and
      purified in a reduced form. In redox buffers, rLIN-12.1 forms only one disulfide
      isomer in the presence of millimolar Ca2+ concentrations, whereas multiple
      disulfide isomers are observed in the presence of Mg2+ and EDTA. Further,
      mutation of conserved residues N1460, D1475, and D1478 to alanine abolishes Ca2+
      dependent folding of this module. Mass spectrometric analysis of partially
      reduced rLIN-12.1 has been used to deduce that disulfide bonds are formed between
      the first and fifth (C1449-C1472), second and fourth (C1454-C1467), and third and
      sixth (C1463-C1479) cysteines of this prototype module. This arrangement is
      distinct from that observed in other modules, such as EGF and LDL-A, that also
      contain three disulfide bonds. One-dimensional proton nuclear magnetic resonance
      shows that Ca2+ induces a dramatic increase in the extent of chemical shift
      dispersion of the native rLIN-12.1 amide protons, as seen for the Ca2+-binding
      LDL-A modules. We conclude that Ca2+ is required both for proper folding and for
      the maintenance of the structural integrity of Notch/LIN-12 modules.

PMID- 10200162
TI  - Alternative roles for putative ice-binding residues in type I antifreeze protein.
AB  - Two sets of variants of type I antifreeze protein have been synthesized to
      investigate the role of Leu and Asn in the activity of this 37-residue alpha
      helix. Leu and Asn flank the central two of four regularly spaced ice-binding Thr
      in the i-1 and i + 3 positions, respectively. All three residues project from the
      same side of the helix to form the protein's putative ice-adsorption site and are
      considered in some models to act together as an "ice-binding motif". Replacement
      of Asn by residues with shorter side chains resulted in either a small loss (Ala)
      or gain (Thr) of antifreeze activity. However, substitution of Asn by its
      slightly larger homologue (Gln) abolished thermal hysteresis activity. The Gln
      containing peptide was very soluble, largely monomeric, and fully helical. Of the
      three variants in which Leu was replaced by Ala, two of the three were more
      active than their Leu-containing counterparts, but all three variants began to
      precipitate as the peptide concentration increased. None of the seven variants
      tested showed dramatic differences in ice crystal morphology from that
      established by the wild type. These results are consistent with a primary role
      for Leu in preventing peptide aggregation at the antifreeze protein
      concentrations (10 mg/mL) normally present in fish serum. Similarly the role for
      Asn may have more to do with enhancing the solubility of these rather hydrophobic
      peptides than of making a stereospecific hydrogen-bonding match to the ice
      lattice as traditionally thought. Nevertheless, the dramatic loss of activity in
      the Asn-to-Gln replacement demonstrates the steric restriction on residues in or
      near the ice-binding site of the peptide.

PMID- 10200163
TI  - Reversible and irreversible hemichrome generation by the oxygenation of
      nitrosylmyoglobin.
AB  - The repeated oxygenation/reduction/nitrosylation of nitrosylmyoglobin produces
      low-spin ferric heme hemichromes which have been characterized by electron spin
      resonance spectroscopy. The predominant myoglobin hemichrome is a chemically
      reversible dihistidyl complex identified by the g values 1.53, 2.21, and 2.97.
      Also present is a low-spin ferric hydroxide derivative which is represented by
      the g values 1.83, 2.18, and 2.59. The formation of these species goes undetected
      by UV-vis spectroscopy, but the oxygenation of myoglobin to metmyoglobin is
      correlated with complete conversion of nitric oxide to nitrate which is released
      following a clear induction period. These results are interpreted in terms of the
      intermediates generated during the MbNO oxygenation reaction.

PMID- 10200164
TI  - Multistep denaturation of Borrelia burgdorferi OspA, a protein containing a
      single-layer beta-sheet.
AB  - Outer surface protein A (OspA) from the Lyme disease spirochete, Borrelia
      burgdorferi, is a dumbbell-shaped protein in which two globular domains are
      connected by a three-stranded beta-sheet segment that is solvent-exposed on both
      faces. Previous studies showed that the whole protein, including the single-layer
      beta-sheet, is highly rigid. To elucidate the folding mechanism and the role of
      the central beta-sheet in the formation of the rigid molecule, we investigated
      the equilibrium thermal denaturation reaction of OspA. We applied differential
      scanning calorimetry, heteronuclear NMR spectroscopy, and solution small-angle X
      ray scattering (SAXS) to characterize the reaction in detail. All three
      techniques revealed that OspA denatures in two separable cooperative transitions.
      NMR measurements on OspA specifically 15N-labeled at Lys residues identified the
      locations of the two folding units and revealed that the C-terminal segment is
      less stable than the remaining N-terminal segment. The boundary between the two
      folding units is located within the central beta-sheet. The interconversion among
      the three folding states (fully folded, C-terminus unfolded, and fully denatured)
      is slow relative to chemical shift differences (<24 Hz), indicating that there
      are significant kinetic barriers in the denaturation reactions. SAXS measurements
      determined the radius of gyration of the native protein to be 25.0 +/- 0.3 A,
      which increases to 34.4 +/- 1.0 A in the first transition, and then to 56.1 +/-
      1.6 A in the second transition. Thus, the intermediate state, in which the C
      terminal folding unit is already denatured, is still compact. These results
      provide a basis for elucidating the folding mechanism of OspA.

PMID- 10200165
TI  - Cofactor requirements and reconstitution of microcin B17 synthetase: a
      multienzyme complex that catalyzes the formation of oxazoles and thiazoles in the
      antibiotic microcin B17.
AB  - In the maturation of the Escherichia coli antibiotic Microcin B17 (MccB17), the
      McbA prepro-antibiotic is modified post-translationally by the multimeric
      microcin synthetase complex (composed of the McbB, -C, and -D proteins), which
      cyclizes four cysteines and four serines to thiazoles and oxazoles, respectively.
      Herein, we report the purification of individual subunits of MccB17 synthetase as
      fusions to maltose binding protein (MBP), and the in vitro reconstitution of
      heterocyclization activity. Preliminary characterization of each subunit reveals
      McbB to be a zinc-containing protein that may catalyze the initial
      cyclodehydration step, and McbC to contain flavin, consistent with an anticipated
      role for a dehydrogenase. We have previously demonstrated that McbD is a
      regulated ATPase/GTPase that may function as a conformational switch.
      Photolabeling experiments with the McbA propeptide now identify McbD as the
      initial site of substrate recognition. Heterocyclization activity was
      reconstituted only by combining all three subunits, demonstrating that each
      protein is required for heterocycle formation. Titration assays indicate that the
      subunits bind to each other with at least micromolar affinities, although McbD
      affords activity only after the MBP tag is proteolytically removed. Subunit
      competition assays with an McbDD147A mutant, which yields a catalytically
      deficient synthetase in vivo, show it to be defective in complex formation,
      whereas the McbBC181A/C184A double mutant, which is also inactive, competitively
      inhibits reconstitution by native McbB. Addition of the HtpG chaperone
      (originally shown to copurify with MccB17 synthetase), does not stimulate
      synthetase reconstitution or heterocyclization activity in vitro. A model for
      synthetase activity is proposed.

PMID- 10200166
TI  - Identifying groups involved in the binding of prephenate to prephenate
      dehydrogenase from Escherichia coli.
AB  - Site-directed mutagenesis was used to investigate the importance of Lys178,
      Arg286, and Arg294 in the binding of prephenate to the bifunctional enzyme
      chorismate mutase-prephenate dehydrogenase. From comparison of the kinetic
      parameters of wild-type enzyme and selected mutants, we conclude that only Arg294
      interacts specifically with prephenate. The R294Q substitution reduces the
      enzyme's affinity for prephenate without affecting V/Et of the dehydrogenase
      reaction or the kinetic parameters of the mutase reaction. Arg294 likely
      interacts with the ring carboxylate at C-1 of prephenate since the dissociation
      constants for a series of inhibitors missing the ring carboxyl group were similar
      for wild-type and R294Q enzymes. The pH dependencies of log (V/KprephenateEt) and
      of pKi for hydroxyphenyllactate show that the wild-type dehydrogenase possesses a
      group with a pK of 8.8 that must be protonated for binding prephenate to the
      enzyme. None of the three conserved residues is this group since its titration is
      observed in the V/KprephenateEt profiles for the mutants K178Q, R286A, and R294Q.
      This group is also seen in the pH-rate profiles of the binding of two substrate
      analogues, hydroxyphenyllactate and deoxoprephenate. Their only common structural
      feature at C-1 is the side chain carboxylate, indicating that the protonated
      residue (pK 8.8) must interact with prephenate's side chain carboxylate. Gdn-HCl
      induced denaturation was conducted on wild-type and selected mutant proteins.
      Unfolding of the wild-type enzyme proceeds through a partially unfolded dimer
      which dissociates into unfolded monomers. The order of stability is wild-type =
      R294Q > K178Q > R286A > K178R. The least unstable mutants have reduced mutase and
      dehydrogenase activities.

PMID- 10200167
TI  - DnrD cyclase involved in the biosynthesis of doxorubicin: purification and
      characterization of the recombinant enzyme.
AB  - Mutations in the Streptomyces peucetius dnrD gene block the ring cyclization
      leading from aklanonic acid methyl ester (AAME) to aklaviketone (AK), an
      intermediate in the biosynthetic pathway to daunorubicin (DNR) and doxorubicin.
      To investigate the role of DnrD in this transformation, its gene was
      overexpressed in Escherichia coli and the DnrD protein was purified to
      homogeneity and characterized. The enzyme was shown to catalyze the conversion of
      AAME to AK presumably via an intramolecular aldol condensation mechanism. In
      contrast to the analogous intramolecular aldol cyclization catalyzed by the TcmI
      protein from the tetracenomycin (TCM) C pathway in Streptomyces glaucescens,
      where a tricyclic anthraquinol carboxylic acid is converted to its fully aromatic
      tetracyclic form, the conversion catalyzed by DnrD occurs after anthraquinone
      formation and requires activation of a carboxylic acid group by esterification of
      aklanonic acid, the AAME precursor. Also, the cyclization is not coupled with a
      subsequent dehydration step that would result in an aromatic ring. As the
      substrates for the DnrD and TcmI enzymes are among the earliest isolable
      intermediates of aromatic polyketide biosynthesis, an understanding of the
      mechanism and active site topology of these proteins will allow one to determine
      the substrate and mechanistic parameters that are important for aromatic ring
      formation. In the future, these parameters may be able to be applied to some of
      the earlier polyketide cyclization processes that currently are difficult to
      study in vitro.

PMID- 10200168
TI  - Involvement of phenylalanine 272 of DNA polymerase beta in discriminating between
      correct and incorrect deoxynucleoside triphosphates.
AB  - DNA polymerase beta is a small monomeric polymerase that participates in base
      excision repair and meiosis [Sobol, R., et al. (1996) Nature 379, 183-186; Plug,
      A., et al. (1997) Proc. Natl. Acad. Sci. U.S.A. 94, 1327-1331]. A DNA polymerase
      beta mutator mutant, F272L, was identified by an in vivo genetic screen
      [Washington, S., et al. (1997) Proc. Natl. Acad. Sci. U.S.A. 94, 1321-1326].
      Residue 272 is located within the deoxynucleoside triphosphate (dNTP) binding
      pocket of DNA polymerase beta according to the known DNA polymerase beta crystal
      structures [Pelletier, H., et al. (1994) Science 264, 1891-1893; Sawaya, M., et
      al. (1997) Biochemistry 36, 11205-11215]. The F272L mutant produces errors at a
      frequency 10-fold higher than that of wild type in vivo and in the in vitro HSV
      tk gap-filling assay. F272L shows an increase in the frequency of both base
      substitution mutations and frameshift mutations. Single-enzyme turnover studies
      of misincorporation by wild type and F272L DNA polymerase beta demonstrate that
      there is a 4-fold decrease in fidelity of the mutant as compared to that of the
      wild type enzyme for a G:A mismatch. The decreased fidelity is due primarily to
      decreased discrimination between the correct and incorrect dNTP during ground
      state binding. These results suggest that the phenylalanine 272 residue is
      critical for maintaining fidelity during the binding of the dNTP.

PMID- 10200169
TI  - Processing of UV damage in vitro by FEN-1 proteins as part of an alternative DNA
      excision repair pathway.
AB  - Ultraviolet (UV) irradiation induces predominantly cyclobutane and (6-4)
      pyrimidine dimer photoproducts in DNA. Several mechanisms for repairing these
      mutagenic UV-induced DNA lesions have been identified. Nucleotide excision repair
      is a major pathway, but mechanisms involving photolyases and DNA glycosylases
      have also been characterized. Recently, a novel UV damage endonuclease (UVDE) was
      identified that initiates an excision repair pathway different from previously
      established repair mechanisms. Homologues of UVDE have been found in eukaryotes
      as well as in bacteria. In this report, we have used oligonucleotide substrates
      containing site-specific cyclobutane pyrimidine dimers and (6-4) photoproducts
      for the characterization of this UV damage repair pathway. After introduction of
      single-strand breaks at the 5' sides of the photolesions by UVDE, these
      intermediates became substrates for cleavage by flap endonucleases (FEN-1
      proteins). FEN-1 homologues from humans, Saccharomyces cerevisiae, and
      Schizosaccharomyces pombe all cleaved the UVDE-nicked substrates at similar
      positions 3' to the photolesions. T4 endonuclease V-incised DNA was processed in
      the same way. Both nicked and flapped DNA substrates with photolesions (the
      latter may be intermediates in DNA polymerase-catalyzed strand displacement
      synthesis) were cleaved by FEN-1. The data suggest that the two enzymatic
      activities, UVDE and FEN-1, are part of an alternative excision repair pathway
      for repair of UV photoproducts.

PMID- 10200170
TI  - Explanation of pre-steady-state kinetics and decreased burst amplitude of HIV-1
      reverse transcriptase at sites of modified DNA bases with an additional,
      nonproductive enzyme-DNA-nucleotide complex.
AB  - The majority of pre-steady-state kinetic investigations with HIV-1 reverse
      transcriptase (HIV-1 RT) have reported substoichiometric bursts (30-50%) of
      product formation in the initial reaction cycle. By using quantitative amino acid
      analysis, we have revised the extinction coefficient of the HIV-1 RT heterodimer
      and show that normal nucleotide incorporation (canonical four bases) proceeds
      with quantitative bursts in the first cycle. We have also modeled our previous
      results with this polymerase, including four situations with 8-oxo-7,8
      dihydroguanine (8-oxoGua) moieties in which substoichiometric bursts (2-35%) were
      observed even after the correction of enzyme concentration by amino acid
      analysis. These include insertion of dATP opposite template 8-oxoGua, insertion
      of (deoxy) 8-oxoGua 5'-triphosphate opposite template C, and extension of primers
      beyond 8-oxoGua-A and 8-oxoGua-C pairs. The "minimal" polymerase mechanism and
      three others were evaluated using KINSIM and FITSIM methods. The latter three
      mechanisms involve a conformationally distinct, inactive polymerase-DNA-dNTP
      complex in equilibrium with the initial ternary complex and a conformationally
      distinct complex leading to phosphodiester bond formation. All three of the
      modified mechanisms fit the observed reaction results, but the minimal mechanism
      did not. Nonfunctional binary complexes (enzyme-DNA) are an alternate explanation
      (to ternary complexes) in some cases. Finally, DNA trapping experiments indicate
      that enzyme does not dissociate from the 8-oxoGua-containing DNA substrate prior
      to phosphodiester bond formation. We conclude that HIV-1 RT is fully active in
      normal nucleotide incorporation and that substoichiometric bursts with modified
      systems are well-described by the existence of nonproductive ternary complexes,
      which can isomerize to productive complexes.

PMID- 10200171
TI  - The crystal structure of a 2-fluorocellotriosyl complex of the Streptomyces
      lividans endoglucanase CelB2 at 1.2 A resolution.
AB  - Glycoside hydrolases have been classified into over 66 families on the basis of
      amino acid sequence. Recently a number of these families have been grouped into
      "clans" which share a common fold and catalytic mechanism [Henrissat, B., and
      Bairoch, A. (1996) Biochem. J. 316, 695-696]. Glycoside hydrolase Clan GH-C
      groups family 11 xylanases and family 12 cellulases, which share the same
      jellyroll topology, with two predominantly antiparallel beta-sheets forming a
      long substrate-binding cleft, and act with net retention of anomeric
      configuration. Here we present the three-dimensional structure of a family 12
      endoglucanase, Streptomyces lividans CelB2, in complex with a 2-deoxy-2
      fluorocellotrioside. Atomic resolution (1.2 A) data allow clear identification of
      two distinct species in the crystal. One is the glycosyl-enzyme intermediate,
      with the mechanism-based inhibitor covalently linked to the nucleophile Glu 120,
      and the other a complex with the reaction product, 2-deoxy-2-fluoro-beta-D
      cellotriose. The active site architecture of the complex provides insight into
      the double-displacement mechanism of retaining glycoside hydrolases and also
      sheds light on the basis of the differences in specificity between family 12
      cellulases and family 11 xylanases.

PMID- 10200172
TI  - Mutation of an active site residue in Escherichia coli uracil-DNA glycosylase:
      effect on DNA binding, uracil inhibition and catalysis.
AB  - The role of the conserved histidine-187 located in the leucine intercalation loop
      of Escherichia coli uracil-DNA glycosylase (Ung) was investigated. Using site
      directed mutagenesis, an Ung H187D mutant protein was created, overproduced,
      purified to apparent homogeneity, and characterized in comparison to wild-type
      Ung. The properties of Ung H187D differed from Ung with respect to specific
      activity, substrate specificity, DNA binding, pH optimum, and inhibition by
      uracil analogues. Ung H187D exhibited a 55000-fold lower specific activity and a
      shift in pH optimum from pH 8.0 to 7.0. Under reaction conditions optimal for
      wild-type Ung (pH 8.0), the substrate preference of Ung H187D on defined single-
      and double-stranded oligonucleotides (25-mers) containing a site-specific uracil
      target was U/G-25-mer > U-25-mer > U/A-25-mer. However, Ung H187D processed these
      same DNA substrates at comparable rates at pH 7.0 and the activity was stimulated
      approximately 3-fold relative to the U-25-mer substrate. Ung H187D was less
      susceptible than Ung to inhibition by uracil, 6-amino uracil, and 5-fluorouracil.
      Using UV-catalyzed protein/DNA cross-linking to measure DNA binding affinity, the
      efficiency of Ung H187D binding to thymine-, uracil-, and apyrimidinic-site
      containing DNA was (dT20) = (dT19-U) >/= (dT19-AP). Comparative analysis of the
      biochemical properties and the X-ray crystallographic structures of Ung and Ung
      H187D [Putnam, C. D., Shroyer, M. J. N., Lundquist, A. J., Mol, C. D., Arvai, A.
      S., Mosbaugh, D. W., and Tainer, J. A. (1999) J. Mol. Biol. 287, 331-346]
      provided insight regarding the role of His-187 in the catalytic mechanism of
      glycosylic bond cleavage. A novel mechanism is proposed wherein the developing
      negative charge on the uracil ring and concomitant polarization of the N1-C1'
      bond is sustained by resonance effects and hydrogen bonding involving the
      imidazole side chain of His-187.

PMID- 10200173
TI  - Comparative FTIR analysis of the microenvironment of in cyanide-treated, high pH
      treated and iron-depleted photosystem II membrane fragments.
AB  - FTIR difference spectra due to light-induced formation were measured in control
      PS II membrane fragments and in samples where the magnetic interaction with the
      non-heme iron center in its high-spin Fe2+ state is eliminated by three different
      methods, i.e., extraction of the non-heme iron center, treatment with cyanide,
      and incubation at high pH (pH = 11). The results obtained reveal that (i) the
      most pronounced band at 1479 cm-1 reflecting the C../--O stretching mode of in
      the semiquinone anion radical remains invariant to "iron depletion" while it
      shifts by 4 and 2 cm-1 to lower frequencies upon cyanide and high pH treatments,
      respectively, (ii) peaks observed in the 2600-3000 cm-1 region which arise from
      Fermi resonance of harmonics and combinations of the imidazole ring modes with
      the hydrogen-bonding NH stretching vibrations are not affected upon iron
      depletion but are lost in cyanide and high pH-treated samples, and (iii) all
      three treatments give rise to some similar changes in the amide I bands of the
      protein backbones and in imidazole ring modes of the coupled histidine. These
      results show that the hydrogen-bonding interaction of is virtually unaffected
      upon non-heme iron depletion; in particular, the strong hydrogen bond between QA
      and a histidine side chain (most likely His 215 of the D2 subunit) is not
      changed. In marked contrast, drastic changes take place in the hydrogen bonding
      between QA and His upon CN- and high pH treatments. The straightforward
      interpretation is that the hydrogen bond is lost upon these treatments. Despite
      the striking difference in the effect of hydrogen-bonding interaction, all three
      treatments lead to similar structural pertubations on the protein conformational
      changes due to formation and ring vibrations of the coupled histidine side chain.
      On the basis of the data presented in the study, it is inferred that, concerning
      the hydrogen bond interaction, the microenvironment of is close to the native
      state when a suitable iron depletion is performed. Accordingly, the previously
      reported conclusion on the hydrogen-bonding pattern of in PS II [MacMillan, F.,
      Lendzian, F., Renger, G., and Lubitz, W. (1995) Biochemistry 34, 8144-8156]
      studied by using iron-depleted preparations most likely reflects the situation in
      an intact PS II.

PMID- 10200174
TI  - Resolution of electrogenic steps coupled to conversion of cytochrome c oxidase
      from the peroxy to the ferryl-oxo state.
AB  - Charge translocation across the membrane coupled to transfer of the third
      electron in the reaction cycle of bovine cytochrome c oxidase (COX) has been
      studied. Flash-induced reduction of the peroxy intermediate (P) to the ferryl-oxo
      state (F) by tris-bipyridyl complex of Ru(II) in liposome-reconstituted COX is
      coupled to several phases of membrane potential generation that have been time
      resolved with the use of an electrometric technique applied earlier in the
      studies of the ferryl-oxo-to-oxidized (F --> O) transition of the enzyme
      [Zaslavsky, D., et al. (1993) FEBS Lett. 336, 389-393]. As in the case of the F -
      > O transition, the electric response associated with photoreduction of P to F
      includes a rapid KCN-insensitive electrogenic phase with a tau of 40-50
      microseconds (reduction of heme a by CuA) and a multiphasic slower part; this
      part is cyanide-sensitive and is assigned to vectorial transfer of protons
      coupled to reduction of oxygen intermediate in the binuclear center. The net KCN
      sensitive phase of the response is approximately 4-fold more electrogenic than
      the rapid phase, which is similar to the characteristics of the F --> O
      electrogenic transition and is consistent with net transmembrane translocation of
      two protons per electron, including vectorial movement of both "chemical" and
      "pumped" protons. The protonic part of the P --> F electric response is faster
      than in the F --> O transition and can be deconvoluted into three exponential
      phases with tau values varying for different samples in the range of 0.25-0.33, 1
      1.5, and 6-7.5 ms at pH 8. Of these three phases, the 1-1.5 ms component is the
      major one contributing 50-60%. The P --> F conversion induced by single electron
      photoreduction of the peroxy state as studied in this work is several times
      slower than the P --> F transition resolved during oxidation of the fully reduced
      oxidase by molecular oxygen. The role of the CuB redox state in controlling the
      rate of P --> F conversion of heme a3 is discussed.

PMID- 10200175
TI  - Identification of a new reaction intermediate in the oxidation of methylamine
      dehydrogenase by amicyanin.
AB  - The two-electron oxidation of tryptophan tryptophylquinone (TTQ) in substrate
      reduced methylamine dehydrogenase (MADH) by amicyanin is known to proceed via an
      N-semiquinone intermediate in which the substrate-derived amino group remains
      covalently attached to TTQ [Bishop, G. R., and Davidson, V. L. (1996)
      Biochemistry 35, 8948-8954]. A new method for the stoichiometric formation of the
      N-semiquinone in vitro has allowed the study of the oxidation of the N
      semiquinone by amicyanin in greater detail than was previously possible.
      Conversion of N-semiquinone TTQ to the quinone requires two biochemical events,
      electron transfer to amicyanin and release of ammonia from TTQ. Using rapid
      scanning stopped-flow spectroscopy, it is shown that this occurs by a sequential
      mechanism in which oxidation to an imine (N-quinone) precedes hydrolysis by water
      and ammonia release. Under certain reaction conditions, the N-quinone
      intermediate accumulates prior to the relatively slow hydrolysis step.
      Correlation of these transient kinetic data with steady-state kinetic data
      indicates that the slow hydrolysis of the N-quinone by water does not occur in
      the steady state. In the presence of excess substrate, the next methylamine
      molecule initiates a nucleophilic attack of the N-quinone TTQ, causing release of
      ammonia that is concomitant with the formation of the next enzyme-substrate
      cofactor adduct. In light of these results, the usually accepted steady-state
      reaction mechanism of MADH is revised and clarified to indicate that reactions of
      the quinone form of TTQ are side reactions of the normal catalytic pathway. The
      relevance of these conclusions to the reaction mechanisms of other enzymes with
      carbonyl cofactors, the reactions of which proceed via Schiff base intermediates,
      is also discussed.

PMID- 10200176
TI  - Interdependency of sequence and positional specificities for cysteine proteases
      of the papain family.
AB  - The specificity of cysteine proteases is characterized by the nature of the amino
      acid sequence recognized by the enzymes (sequence specificity) as well as by the
      position of the scissile peptide bond (positional specificity, i.e.,
      endopeptidase, aminopeptidase, or carboxypeptidase). In this paper, the
      interdependency of sequence and positional specificities for selected members of
      this class of enzymes has been investigated using fluorogenic substrates where
      both the position of the cleavable peptide bond and the nature of the sequence of
      residues in P2-P1 are varied. The results show that cathepsins K and L and
      papain, typically considered to act strictly as endopeptidases, can also display
      dipeptidyl carboxypeptidase activity against the substrate Abz-FRF(4NO2)A and
      dipeptidyl aminopeptidase activity against FR-MCA. In some cases the activity is
      even equal to or greater than that observed with cathepsin B and DPP-I
      (dipeptidyl peptidase I), which have been characterized previously as
      exopeptidases. In contrast, the exopeptidase activities of cathepsins K and L and
      papain are extremely low when the P2-P1 residues are A-A, indicating that, as
      observed for the normal endopeptidase activity, the exopeptidase activities rely
      heavily on interactions in subsite S2 (and possibly S1). However, cathepsin B and
      DPP-I are able to hydrolyze substrates through the exopeptidase route even in
      absence of preferred interactions in subsites S2 and S1. This is attributed to
      the presence in cathepsin B and DPP-I of specific structural elements which serve
      as an anchor for the C- or N-terminus of a substrate, thereby allowing favorable
      enzyme-substrate interaction independently of the P2-P1 sequence. As a
      consequence, the nature of the residue at position P2 of a substrate, which is
      usually the main factor determining the specificity for cysteine proteases of the
      papain family, does not have the same contribution for the exopeptidase
      activities of cathepsin B and DPP-I.

PMID- 10200177
TI  - Contributions of residues of pancreatic phospholipase A2 to interfacial binding,
      catalysis, and activation.
AB  - Primary rate and equilibrium parameters for 60 site-directed mutants of bovine
      pancreatic phospholipase A2 (PLA2) are analyzed so incremental contributions of
      the substitution of specific residues can be evaluated. The magnitude of the
      change is evaluated so a functional role in the context of the N- and C-domains
      of PLA2 can be assigned, and their relationship to the catalytic residues and to
      the i-face that makes contact with the interface. The effect of substitutions and
      interfacial charge is characterized by the equilibrium dissociation constant for
      dissociation of the bound enzyme from the interface (Kd), the dissociation
      constant for dissociation of a substrate mimic from the active site of the bound
      enzyme (KL), and the interfacial Michaelis constants, KM and kcat. Activity is
      lost (>99.9%) on the substitution of H48 and D49, the catalytic residues. A more
      than 95% decrease in kcat is seen with the substitution of F5, I9, D99, A102, or
      F106, which form the substrate binding pocket. Certain residues, which are not
      part of the catalytic site or the substrate binding pocket, also modulate kcat.
      Interfacial anionic charge lowers Kd, and induces kcat activation through K56,
      K53, K119, or K120. Significant changes in KL are seen by the substitution of N6,
      I9, F22, Y52, K53, N71, Y73, A102, or A103. Changes in KM [=(k2+k-1)/k1] are
      attributed to kcat (=k2) and KL (=k-1/k1). Some substitutions change more than
      one parameter, implying an allosteric effect of the binding to the interface on
      KS, and the effect of the interfacial anionic charge on kcat. Interpreted in the
      context of the overall structure, results provide insights into the role of
      segments and domains in the microscopic events of catalytic turnover and
      processivity, and their allosteric regulation. We suggest that the interfacial
      recognition region (i-face) of PLA2, due to the plasticity of certain segments
      and domains, exercises an allosteric control on the substrate binding and
      chemical step.

PMID- 10200178
TI  - Site-specific characterization of the N-linked glycans of murine prion protein by
      high-performance liquid chromatography/electrospray mass spectrometry and
      exoglycosidase digestions.
AB  - The murine prion protein PrP gene encodes a protein of 254 amino acids with two
      consensus sites for Asn-linked glycosylation at codons 180 and 196. A partial
      site-specific study of the N-linked glycans from hamster PrP has previously been
      carried out by mass spectrometry [Stahl, N., Baldwin, M. A., Teplow, D. B., Hood,
      L., Gibson, B. W., Burlingame, A. L., and Prusiner, S. B. (1993) Biochemistry 32,
      1991-2002] and revealed that the glycosylation at Asn-181 (equivalent to mouse
      180) is heterogeneous, comprising over 30 glycoforms. The identification of the
      glycosylated peptide spanning Asn-197 was not reported. Recent technical advances
      in electrospray mass spectrometry now provide the sensitivity to detect low
      femtomole quantities of glycopeptides with >5000 mass resolution and 30 ppm mass
      measurement [Medzihradszky, K. F., Besman, M. J., and Burlingame, A. L. (1998)
      Rapid Commun. Mass Spectrom. 12, 472-478]. This performance coupled with stepwise
      exoglycosidase digestion has been employed to establish the differential nature
      of the structural complexity (glycoforms) of the glycans at Asn-180 and Asn-196
      from a single strain infected with the ME7 strain. Some sixty structures have
      been found characterized by neutral and sialylated bi-, tri-, and tetraantennary
      complex-type bearing outer-arm alpha(1-3)-fucosylation (the Lewisx and sialyl
      Lewisx epitopes), core alpha(1,6) fucosylation, and the presence of terminal
      HexNAc residues. The Lewisx trisaccharide is the major nonreducing structure at
      Asn-180, and significant amounts of both Lewisx and sialyl Lewisx epitopes are
      observed at Asn-196. The abundance of the Lewisx and sialyl Lewisx epitopes on
      murine PrPSc may indicate a role for these structures in the normal function of
      PrPC or the pathophysiology of PrPSc.

PMID- 10200180
TI  - N1-(5'-Phosphoribosyl)adenosine-5'-monophosphate cyclohydrolase: purification and
      characterization of a unique metalloenzyme 

PMID- 10200179
TI  - pKa values and the pH dependent stability of the N-terminal domain of L9 as
      probes of electrostatic interactions in the denatured state. Differentiation
      between local and nonlocal interactions.
AB  - pKa values were measured for the 6 carboxylates in the N-terminal domain of L9
      (NTL9) by following NMR chemical shifts as a function of pH. The contribution of
      each carboxylate to the pH dependent stability of NTL9 was estimated by comparing
      the pKa values for the native and denatured state of the protein. A set of
      peptides with sequences derived from NTL9 were used to model the denatured state.
      In the protein fragments, the pKa values measured for the aspartates varied
      between 3.8 and 4.1 and the pKa values measured for the glutamates varied between
      4.1 and 4.6. These results indicate that the local sequence can significantly
      influence pKa values in the denatured state and highlight the difficulties in
      using standard pKa values derived from small compounds. Calculations based on the
      measured pKa values suggest that the free energy of unfolding of NTL9 should
      decrease by 4.4 kcal mol-1 when the pH is lowered from 6 to 2. In contrast, urea
      and thermal denaturation experiments indicate that the stability of the protein
      decreases by only 2.6 kcal mol-1 when the carboxylates are protonated. This
      discrepancy indicates that the protein fragments are not a complete
      representation of the denatured state and that nonlocal sequence effects perturb
      the pKa's in the denatured state. Increasing the salt concentration from 100 to
      750 mM NaCl removes the discrepancy between the stabilities derived from
      denaturation experiments and the stability changes calculated from the pKa
      values. At high concentrations of salt there is also less variation of the pKa
      values measured in the protein fragments. Our results argue that in the denatured
      state of NTL9 there are electrostatic interactions between groups both local and
      nonlocal in primary sequence.

PMID- 10200181
TI  - Nitric oxide inhibits L-type Ca2+ current in glomus cells of the rabbit carotid
      body via a cGMP-independent mechanism.
AB  - Previous studies have shown that nitric oxide (NO) inhibits carotid body sensory
      activity. To begin to understand the cellular mechanisms associated with the
      actions of NO in the carotid body, we monitored the effects of NO donors on the
      macroscopic Ca2+ current in glomus cells isolated from rabbit carotid bodies.
      Experiments were performed on freshly dissociated glomus cells from adult rabbit
      carotid bodies using the whole cell configuration of the patch-clamp technique.
      The NO donors sodium nitroprusside (SNP; 600 microM, n = 7) and spermine nitric
      oxide (SNO; 100 microM, n = 7) inhibited the Ca2+ current in glomus cells in a
      voltage-independent manner. These effects of NO donors were rapid in onset and
      peaked within 1 or 2 min. In contrast, the outward K+ current was unaffected by
      SNP (600 microM, n = 6), indicating that the inhibition by SNP was not a
      nonspecific membrane effect. 2-(4-carboxyphenyl)-4,4,5, 5-tetramethyl-imidazoline
      1-oxyl-3-oxide (carboxy-PTIO; 500 microM), an NO scavenger, prevented inhibition
      of the Ca2+ current by SNP (n = 7), whereas neither superoxide dismutase (SOD;
      2,000 U/ml, n = 4), a superoxide scavenger, nor sodium hydrosulfite (SHS; 1 mM, n
      = 7), a reducing agent, prevented inhibition of the Ca2+ current by SNP. However,
      SNP inhibition of the Ca2+ current was reversible in the presence of either SOD
      or SHS. These results suggest that NO itself inhibits Ca2+ current in a
      reversible manner and that subsequent formation of peroxynitrites results in
      irreversible inhibition. SNP inhibition of the Ca2+ current was not affected by
      30 microM LY 83, 583 (n = 7) nor was it mimicked by 600 microM 8-bromoguanosine
      3':5'-cyclic monophosphate (8-Br-cGMP; n = 6), suggesting that the effects of NO
      on the Ca2+ current are mediated, in part, via a cGMP-independent mechanism. N
      ethylmaleimide (NEM; 2.5 mM, n = 6) prevented the inhibition of the Ca2+ current
      by SNP, indicating that SNP is acting via a modification of sulfhydryl groups on
      Ca2+ channel proteins. Norepinephrine (NE; 10 microM) further inhibited the Ca2+
      current in the presence of NEM (n = 7), implying that NEM did not nonspecifically
      eliminate Ca2+ current modulation. Nisoldipine, an L-type Ca2+ channel blocker (2
      microM, n = 6), prevented the inhibition of Ca2+ current by SNP, whereas omega
      conotoxin GVIA, an N-type Ca2+ channel blocker (1 microM, n = 9), did not prevent
      the inhibition of Ca2+ current by SNP. These results demonstrate that NO inhibits
      L-type Ca2+ channels in adult rabbit glomus cells, in part, due to a modification
      of calcium channel proteins. The inhibition might provide one plausible mechanism
      for efferent inhibition of carotid body activity by NO.

PMID- 10200182
TI  - Multijoint muscle regulation mechanisms examined by measured human arm stiffness
      and EMG signals.
AB  - Stiffness properties of the musculo-skeletal system can be controlled by
      regulating muscle activation and neural feedback gain. To understand the
      regulation of multijoint stiffness, we examined the relationship between human
      arm joint stiffness and muscle activation during static force control in the
      horizontal plane by means of surface electromyographic (EMG) studies. Subjects
      were asked to produce a specified force in a specified direction without
      cocontraction or they were asked to keep different cocontractions while producing
      or not producing an external force. The stiffness components of shoulder, elbow,
      and their cross-term and the EMG of six related muscles were measured during the
      tasks. Assuming that the EMG reflects the corresponding muscle stiffness, the
      joint stiffness was predicted from the EMG by using a two-link six-muscle arm
      model and a constrained least-square-error regression method. Using the
      parameters estimated in this regression, single-joint stiffness (diagonal terms
      of the joint-stiffness matrix) was decomposed successfully into biarticular and
      monoarticular muscle components. Although biarticular muscles act on both
      shoulder and elbow, they were found to covary strongly with elbow monoarticular
      muscles. The preferred force directions of biarticular muscles were biased to the
      directions of elbow monoarticular muscles. Namely, the elbow joint is regulated
      by the simultaneous activation of monoarticular and biarticular muscles, whereas
      the shoulder joint is regulated dominantly by monoarticular muscles. These
      results suggest that biarticular muscles are innervated mainly to control the
      elbow joint during static force-regulation tasks. In addition, muscle regulation
      mechanisms for static force control tasks were found to be quite different from
      those during movements previously reported. The elbow single-joint stiffness was
      always higher than cross-joint stiffness (off-diagonal terms of the matrix) in
      static tasks while elbow single-joint stiffness is reported to be sometimes as
      small as cross-joint stiffness during movement. That is, during movements, the
      elbow monoarticular muscles were occasionally not activated when biarticular
      muscles were activated. In static tasks, however, monoarticular muscle components
      in single-joint stiffness were increased considerably whenever biarticular muscle
      components in single- and cross-joint stiffness increased. These observations
      suggest that biarticular muscles are not simply coupled with the innervation of
      elbow monoarticular muscles but also are regulated independently according to the
      required task. During static force-regulation tasks, covariation between
      biarticular and elbow monoarticular muscles may be required to increase stability
      and/or controllability or to distribute effort among the appropriate muscles.

PMID- 10200183
TI  - In vivo assessment of the midbrain raphe nuclear regulation of serotonin release
      in the hamster suprachiasmatic nucleus.
AB  - Serotonin (5-HT) plays important regulatory roles in mammalian circadian
      timekeeping; however, little is known concerning the regulation of serotonergic
      activity in the circadian clock located in the suprachiasmatic nuclei (SCN). By
      using in vivo microdialysis to measure 5-HT release we demonstrated that
      electrical or pharmacological stimulations of the dorsal or median raphe nuclei
      (DRN and MRN, respectively) can alter basal release of 5-HT in the hamster SCN.
      There were similar increases in SCN 5-HT release after electrical stimulation of
      either the MRN or DRN, indicating that both could contribute to the serotonergic
      activity in the SCN. Systemic pretreatment with the 5-HT antagonist metergoline
      abolished DRN-induced SCN 5-HT release but had little effect on MRN-induced SCN 5
      HT release, suggesting different pathways for these nuclei in regulating 5-HT
      output in the SCN. Microinjections of the 5-HT1A autoreceptor agonist 8-OH-DPAT
      or antagonist WAY 100635 into the MRN caused significant inhibition and
      stimulation of SCN 5-HT release, respectively. Both drugs had substantially less
      effect in the DRN. These differential drug actions indicate that somatodendritic
      5-HT1A autoreceptors on MRN neurons provide the prominent raphe autoregulation of
      5-HT output in the SCN. Collectively the current results are evidence that DRN as
      well as MRN neurons can contribute to the regulation of 5-HT release in the
      hamster SCN. On the basis of the current observations and those from recent
      anatomic tracing studies of serotonergic projections to SCN it is hypothesized
      that DRN input to the SCN could be mediated by a DRN --> MRN --> SCN pathway
      involving a 5-HT-sensitive multisynaptic interaction between the DRN and MRN
      neurons.

PMID- 10200184
TI  - Outward currents influencing bursting dynamics in guinea pig trigeminal
      motoneurons.
AB  - To initiate and maintain bursts (and plateau potentials) in the presence of
      serotonin, guinea pig trigeminal motoneurons utilize L-type Ca2+ and persistent
      Na+ inward currents. However, the intrinsic currents that contribute to burst
      termination and determine the duration of the interburst interval are unknown.
      Therefore we investigated the roles of outward currents, whose slow activation is
      coupled to cytosolic cation (Ca2+ and Na+) accumulation. First we examined a Ca2+
      dependent K+ current (IK-Ca) with apamin and Ba2+-substituted, low-Ca2+ solution.
      Blockade of IK-Ca lengthened burst duration and cycle time but did not abolish
      bursting. Next we studied the Na+/K+-ATPase pump current (Ip) with cardiac
      glycosides. In the presence of apamin or low-Ca2+/Ba2+ solution, blocking Ip
      (with ouabain or strophanthidin) decreased both burst duration and cycle time and
      ultimately transformed bursting into tonic spiking. We conclude that IK-Ca and Ip
      contribute to burst termination in trigeminal motoneurons. These currents
      influence temporal bursting properties such as burst duration and cycle time and
      may help determine the phasic activity of motoneurons during rhythmic oral-motor
      behaviors.

PMID- 10200185
TI  - Transformations in embryonic motility in chick: kinematic correlates of type I
      and II motility at E9 and E12.
AB  - Soon after hatching, chicks exhibit an array of adaptive, coordinated behaviors.
      Chick embryos also acquire nearly 18 days of movement experience, referred to as
      embryonic motility, before hatching. The chick expresses three forms of motility,
      types I, II, and III, and each emerges at a different stage of embryonic
      development. Although much is known about the mechanisms associated with motility
      at early embryonic stages and at the onset of hatching, the transformations in
      behavior and underlying mechanisms are not fully understood. Thus the purpose of
      this study was to determine how motility is modified during the first expected
      transformation, from type I to type II. It was hypothesized that kinematic
      features for motility at embryonic day 12 (E12) would differ significantly from
      features at E9 because type II motility emerges during E11. Embryos were video
      taped for extended intervals in ovo at E9 or E12 and entire sequences of motility
      were computer digitized for kinematic analyses. Results reported here indicate
      that several of the kinematic features characteristic of motility at E9 are also
      reliable features at E12. On the basis of these findings, a kinematic definition
      of type I motility is posed for use in subsequent behavioral studies. Several
      parameters distinguished motility at E12 from E9. The most notable difference
      between ages was the less regular timing of repetitive limb movements at E12, a
      finding consistent with recent reports suggesting early motility is an emergent
      product of a transient neural network rather than a specialized pattern
      generator. As predicted from established definitions for type II motility,
      startle-like movements were common at E12; however, they also were present in
      many kinematic plots at E9, suggesting the discreet age-dependent boundaries in
      the established definition for type II motility may require modification. Some
      age-related differences, such as increased intralimb coordination and excursion
      velocity, may be prerequisites for adaptive behavior after hatching.

PMID- 10200186
TI  - Contribution of active zone subpopulation of vesicles to evoked and spontaneous
      release.
AB  - Our previous work on Drosophila synapses has suggested that two vesicle
      populations possessing different recycling pathways, a fast pathway emanating
      from the active zone and a slower pathway emanating from sites away from the
      active zone, exist in the terminal. The difference in recycling time between
      these two pathways has allowed us to create a synapse that possesses the small,
      active zone subpopulation without the larger, nonactive zone population. Synapses
      were depleted using the temperature-sensitive endocytosis mutant, shibire, which
      reversibly blocks vesicle recycling at the restrictive temperature. In the
      depleted state, both the excitatory junction potential (EJP) and spontaneous
      release are abolished. After shibire-induced depletion, the active zone
      population begins to reform within 30 s at the permissive temperature, whereas
      the nonactive zone population does not begin to reform until approximately 10-15
      min later. Evoked release recovered at approximately the same time as the active
      zone population. During the time when the active zone population existed in the
      terminal without the nonactive zone population, enough transmitter release was
      available to sustain a normal evoked response for many minutes at frequencies
      above those produced during normal activity (flight) by this motor neuron. When
      only the active zone population existed in the terminal, the frequency of
      spontaneous release was greatly attenuated and possessed abnormal release
      characteristics. Spontaneous release recovered its predepletion frequency and
      release characteristics only after the nonactive zone population was reformed.

PMID- 10200187
TI  - Subtype-specific effects of lithium on glutamate receptor function.
AB  - We report that substitution of sodium with lithium (Li+) in the extracellular
      solution causes subtype-specific changes in the inward and outward currents of
      glutamate receptors (GluRs), without a shift in reversal potential. Li+ produces
      an increase of inward and outward currents of alpha-amino-3-hydroxy-5-methyl-4
      isoxazole propionate receptors and decreases in the currents of kainate (KA) and
      N-methyl-D-aspartate receptors. The greatest effect of Li+ was observed with
      GluR3. A concentration-response curve for GluR3 reveals that the potentiation
      caused by Li+ is greatest at saturating agonist concentrations. GluR1, which
      shows no potentiation by Li+ at 100 microM KA, shows a small but significant
      potentiation at saturating KA and glutamate concentrations. The effects of Li+ on
      outward current, where Li+ is not the primary charge carrier, and the lack of
      reversal potential shift argue for a mechanism of potentiation not associated
      with Li+ permeation. This potentiation of current is specific for Li+ because
      rubidium, although causing an increase of inward current, shifted the reversal
      potential and did not increase outward current. The effects of Li+ are different
      for KA, a weak desensitizing agonist, and glutamate, a strong desensitizing
      agonist, suggesting that Li+ might interact with a mechanism of desensitization.
      By using cyclothiazide (CTZ) to reduce desensitization of GluR3, we find that for
      low concentrations of KA and glutamate potentiation of the response by a
      combination of CTZ and Li+ is no greater than by CTZ or Li+ alone. However, at
      high concentrations of agonist, the potentiation of the response by a combination
      of CTZ and Li+ is significantly greater than by CTZ or Li+ alone. This
      potentiation was additive for glutamate but not for KA. At high agonist
      concentration in the presence of CTZ, the intrinsically lower desensitization
      produced with KA-evoked responses may preclude Li+ from potentiating the current
      to the same degree as it can potentiate glutamate-evoked responses. The additive
      effects of CTZ and Li+ were unique to the flop variant of GluR3.

PMID- 10200188
TI  - Recovery of locomotion after ventral and ventrolateral spinal lesions in the cat.
      II. Effects of noradrenergic and serotoninergic drugs.
AB  - The effects of serotoninergic and noradrenergic drugs (applied intrathecally) on
      treadmill locomotion were evaluated in two adult cats subjected to a ventral and
      ventrolateral spinal lesion (T13). Despite the extensive spinal lesion, severely
      damaging important descending pathways such as the reticulo- and vestibulospinal
      tracts, both cats recovered quadrupedal voluntary locomotion. As detailed in a
      previous paper, the locomotor recovery occurred in three stages defined as early
      period, when the animal could not walk with its hindlimbs, recovery period, when
      progressive improvement occurred, and plateau period, when a more stable
      locomotor performance was observed. At this latter stage, the cats suffered from
      postural and locomotor deficits, such as poor lateral stability, irregular
      stepping of the hindlimbs, and inconsistent homolateral fore- and hindlimb
      coupling. The present study aimed at evaluating the potential of serotoninergic
      and/or noradrenergic drugs to improve the locomotor abilities in the early and
      late stages. Both cats were implanted chronically with an intrathecal cannula and
      electromyographic (EMG) electrodes, which allowed determination, under similar
      recording conditions, of the locomotor performance pre- and postlesion and
      comparisons of the effects of different drugs. EMG and kinematic analyses showed
      that norepinephrine (NE) injected in early and plateau periods improved the
      regularity of the hindlimb stepping and stabilized the interlimb coupling,
      permitting to maintain constant locomotion for longer periods of time.
      Methoxamine, the alpha1-agonist (tested only at the plateau period), had similar
      effects. In contrast, the alpha2-agonist, clonidine, deteriorated walking.
      Serotoninergic drugs, such as the neurotransmitter itself, serotonin (5HT), the
      precursor 5-hydroxytryptophan (5HTP), and the agonist quipazine improved the
      locomotion by increasing regularity of the hindlimb stepping and by increasing
      the step cycle duration. In contrast, the 5HT1A agonist 8-hydroxy
      dipropylaminotetralin (DPAT) caused foot drag in one of the cats, resulting in
      frequent stumbling. Injection of combination of methoxamine and quipazine
      resulted in maintained, regular stepping with smooth movements and good lateral
      stability. Our results show that the effects of drugs can be integrated to the
      residual voluntary locomotion and improve some of its postural aspects. However,
      this work shows clearly that the effects of drugs (such as clonidine) may depend
      on whether or not the spinal lesion is complete. In a clinical context, this may
      suggest that different classes of drugs could be used in patients with different
      types of spinal cord injuries. Possible mechanisms underlying the effect of
      noradrenergic and serotoninergic drugs on the locomotion after partial spinal
      lesions are discussed.

PMID- 10200189
TI  - Impact of network activity on the integrative properties of neocortical pyramidal
      neurons in vivo.
AB  - During wakefulness, neocortical neurons are subjected to an intense synaptic
      bombardment. To assess the consequences of this background activity for the
      integrative properties of pyramidal neurons, we constrained biophysical models
      with in vivo intracellular data obtained in anesthetized cats during periods of
      intense network activity similar to that observed in the waking state. In
      pyramidal cells of the parietal cortex (area 5-7), synaptic activity was
      responsible for an approximately fivefold decrease in input resistance (Rin), a
      more depolarized membrane potential (Vm), and a marked increase in the amplitude
      of Vm fluctuations, as determined by comparing the same cells before and after
      microperfusion of tetrodotoxin (TTX). The model was constrained by measurements
      of Rin, by the average value and standard deviation of the Vm measured from
      epochs of intense synaptic activity recorded with KAc or KCl-filled pipettes as
      well as the values measured in the same cells after TTX. To reproduce all
      experimental results, the simulated synaptic activity had to be of relatively
      high frequency (1-5 Hz) at excitatory and inhibitory synapses. In addition,
      synaptic inputs had to be significantly correlated (correlation coefficient
      approximately 0.1) to reproduce the amplitude of Vm fluctuations recorded
      experimentally. The presence of voltage-dependent K+ currents, estimated from
      current-voltage relations after TTX, affected these parameters by <10%. The model
      predicts that the conductance due to synaptic activity is 7-30 times larger than
      the somatic leak conductance to be consistent with the approximately fivefold
      change in Rin. The impact of this massive increase in conductance on dendritic
      attenuation was investigated for passive neurons and neurons with voltage
      dependent Na+/K+ currents in soma and dendrites. In passive neurons, correlated
      synaptic bombardment had a major influence on dendritic attenuation. The
      electrotonic attenuation of simulated synaptic inputs was enhanced greatly in the
      presence of synaptic bombardment, with distal synapses having minimal effects at
      the soma. Similarly, in the presence of dendritic voltage-dependent currents, the
      convergence of hundreds of synaptic inputs was required to evoke action
      potentials reliably. In this case, however, dendritic voltage-dependent currents
      minimized the variability due to input location, with distal apical synapses
      being as effective as synapses on basal dendrites. In conclusion, this
      combination of intracellular and computational data suggests that, during low
      amplitude fast electroencephalographic activity, neocortical neurons are
      bombarded continuously by correlated synaptic inputs at high frequency, which
      significantly affect their integrative properties. A series of predictions are
      suggested to test this model.

PMID- 10200190
TI  - Detection of vibration transmitted through an object grasped in the hand.
AB  - A tool or probe often functions as an extension of the hand, transmitting
      vibrations to the hand to produce a percept of the object contacting the tool or
      probe. This paper reports the psychophysical results of a combined psychophysical
      and neurophysiological study of the perception of vibration transmitted through a
      cylinder grasped in the hand. In the first part of the psychophysical study, 19
      subjects grasped a cylinder, 32 mm diam, with an embedded motor that caused
      vibration parallel to the axis of the cylinder. The relationship between
      threshold and frequency was the traditional U-shaped function with a minimum
      between 150 and 200 Hz. Except a study by Bekesy in which subjects grasped a rod
      that vibrated parallel to the skin surface, thresholds above 20 Hz were lower and
      the slopes were steeper than any reported previously. Thresholds were <0.01
      microm in some subjects. Data from both the psychophysical and the
      neurophysiological studies suggest that detection performance at frequencies >20
      Hz was based on activity in Pacinian afferents. The extreme sensitivity compared
      with previous reports may have resulted from differences in contact area,
      direction of vibration, contact force, and the shape of the stimulus probe. The
      effects of each of these variables were studied. At 40 and 300 Hz (frequencies
      near the lower and upper end of the Pacinian range) thresholds were 9.8 and 18.5
      dB (68 and 88%) lower, respectively, when subjects grasped the cylinder than when
      a 1-mm-diam probe vibrated perpendicular to the skin. These differences were
      accounted for as follows: 1) thresholds at a single fingerpad obtained with the
      large cylindrical surface were, on average, 20 and 60% lower, respectively, than
      thresholds with the punctate probe; 2) thresholds at the palm were, on average,
      15 and 40% lower, respectively, than at the fingerpads; 3) thresholds obtained
      when the subjects grasped the cylinder averaged 40 and 20% less, respectively,
      than when the cylinder contacted only the palm; 4) thresholds with the cylinder
      contacting two fingers were 10 and 30% lower, respectively, than thresholds with
      the cylinder contacting a single finger; and 5) thresholds with vibration
      parallel to the skin surface were, on average, 10 and 30% lower, respectively,
      than thresholds with vibration perpendicular to the skin. Contact force, which
      was varied from 0.05 to 1.0 N, had no effect.

PMID- 10200191
TI  - Inhibitory control of LTP and LTD: stability of synapse strength.
AB  - Although much is known about the induction of synaptic plasticity, the
      persistence of memories suggests the importance of understanding factors that
      maintain synaptic strength and prevent unwanted synaptic changes. Here we present
      evidence that recurrent inhibitory connections in the CA1 region of hippocampus
      may contribute to this task by modulating the relative ability to induce long
      term potentiation and depression (LTP and LTD). Bath application of the gamma
      aminobutyric acid (GABA) type A agonist muscimol to hippocampal slices increased
      the range of frequencies that produce LTD, whereas in the presence of the GABA
      type A antagonist picrotoxin LTD was induced only at very low stimulation
      frequencies (0.25-0.5 Hz). Because one source of GABAergic input to CA1 pyramidal
      cells is via recurrent inhibition, we tested the prediction that elevated
      postsynaptic spike activity would increase feedback GABA inhibition and favor the
      induction of LTD. By using an induction stimulation of 8 Hz, which alone produced
      no net change in synaptic strength, we found that stimulation presented during
      antidromic activation of pyramidal cell spikes induced LTD. This effect was
      blocked by picrotoxin. The influence of recurrent inhibition on LTP and LTD
      displays properties that may decrease the potential for self-reinforcing, runaway
      changes in synapse strength. A mechanism of this sort may help maintain patterns
      of synaptic strengths despite the ongoing opportunities for plasticity produced
      by synapse activation.

PMID- 10200192
TI  - Characterization of a Na+-dependent betaine transporter with Cl- channel
      properties in squid motor neurons.
AB  - Most marine invertebrates, including squids, use transporters to accumulate
      organic osmolytes such as betaine, to prevent water loss when exposed to elevated
      salinity. Although a limited number of flux studies have shown the Na+ dependence
      of betaine transport, nothing is known about the electrogenic properties of
      osmolyte transporters. We used whole cell and perforated-patch voltage-clamp
      techniques to characterize the electrical properties of the betaine transporter
      in giant fiber lobe motor neurons of the squid Lolliguncula brevis. Betaine
      activated a large, Cl--selective current that was reversibly blocked by 100
      microM niflumic acid (97 +/- 2% block after 40 s, SD; n = 7) and partially
      inhibited by 500 microM SITS (29 +/- 11%; n = 5). The Cl- current was Na+
      dependent and was virtually eliminated by isotonic replacement of Na+ with Li+,
      NMDG+, or Tris+. Concentration-response data revealed an EC50 in a
      physiologically relevant range for these animals of 5.1 +/- 0.9 mM (n = 11). In
      vertebrates, the betaine transporter is structurally related to the GABA
      transporter, and although GABA did not directly activate the betaine-induced
      current, it reversibly reduced betaine responses by 34 +/- 14% (n = 8). Short
      term changes in osmolality alone did not activate the Cl- current, but when
      combined with betaine, Cl- currents increased in hypertonic solutions and
      decreased in hypotonic solutions. Activation of the betaine transporter and Cl-
      current in hypertonic conditions may affect both volume regulation and
      excitability in L. brevis motor neurons. This study is the first report of a
      novel betaine transporter in neurons that can act as a Cl- channel.

PMID- 10200193
TI  - Functional GABAA receptor heterogeneity of acutely dissociated hippocampal CA1
      pyramidal cells.
AB  - CA1 pyramidal cells were voltage clamped, and GABA was applied to individual
      cells with a modified U-tube, rapid drug application system. With Vh = -50 mV,
      inward currents elicited by 10 microM GABA were inhibited by GABAA receptor
      (GABAR) antagonists and were baclofen insensitive, suggesting that GABA actions
      on isolated CA1 pyramidal cells were GABAR mediated. GABA concentration-response
      curves averaged from all cells were fitted best with a two-site equation,
      indicating the presence of at least two GABA binding sites, a higher-affinity
      site (EC50-1 = 11.0 microM) and a lower-affinity site (EC50-2 = 334.2 microM), on
      two or more populations of cells. The effects of GABAR allosteric modulators on
      peak concentration-dependent GABAR currents were complex and included monophasic
      (loreclezole) or multiphasic (diazepam) enhancement, mixed enhancement/inhibition
      (DMCM, zolpidem) or multiphasic inhibition (zinc). Monophasic (70% of cells) or
      biphasic (30% of cells) enhancement of GABAR currents by diazepam suggested three
      different sites on GABARs (EC50-1 =1.8 nM; EC50-2 = 75.8 nM; EC50-3 = 275.9 nM)
      revealing GABAR heterogeneity. The imidazopyridine zolpidem enhanced GABAR
      currents in 70% of cells with an EC50 = 222.5 nM, suggesting a predominance of
      moderate affinity alpha2 (or alpha3-) subtype-containing BZ Type IIA receptors. A
      small fraction of cells (10%) had a high affinity for zolpidem, something that is
      suggestive of alpha1 subtype-containing BZ Type I receptors. The remaining 30% of
      cells were insensitive to or inhibited by zolpidem, suggesting the presence of
      alpha5 subtype-containing BZ Type IIB receptors. Whether BZ Type I and Type II
      receptors coexist could not be determined. The beta-carboline methyl 6,7
      dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) inhibited GABAR currents in
      all cells at midnanomolar concentrations, but in addition, potentiated GABAR
      currents in some cells at low nanomolar concentrations, characterizing two groups
      of cells, the latter likely due to functional assembly of
      alpha5betaxgamma2GABARs. In all cells, GABAR currents were moderately sensitive
      (EC50 = 9 microM) to loreclezole, consistent with a relatively greater beta3
      subtype, than beta1 subtype, subunit mRNA expression. Two populations of cells
      were identified based on their sensitivities to zinc(IC50 = 28 and 182 microM),
      suggesting the presence of at least two GABAR isoforms including
      alpha5beta3gamma2 GABARs. Consistent with the heterogeneity of expression of
      GABAR subunit mRNA and protein in the hippocampus and based on their differential
      responses to GABA and to allosteric modulators, distinct populations of CA1
      pyramidal cells likely express multiple, functional GABAR isoforms.

PMID- 10200195
TI  - Oculomotor tracking in two dimensions.
AB  - Results from studies of oculomotor tracking in one dimension have indicated that
      saccades are driven primarily by errors in position, whereas smooth pursuit
      movements are driven primarily by errors in velocity. To test whether this result
      generalizes to two-dimensional tracking, we asked subjects to track a target that
      moved initially in a straight line then changed direction. We found that the
      general premise does indeed hold true; however, the study of oculomotor tracking
      in two dimensions provides additional insight. The first saccade was directed
      slightly in advance of target location at saccade onset. Thus its direction was
      related primarily to angular positional error. The direction of the smooth
      pursuit movement after the saccade was related linearly to the direction of
      target motion with an average slope of 0.8. Furthermore the magnitude and
      direction of smooth pursuit velocity did not change abruptly; consequently the
      direction of smooth pursuit appeared to rotate smoothly over time.

PMID- 10200196
TI  - Citrate ions enhance taste responses to amino acids in the largemouth bass.
AB  - The glossopharyngeal (IX) taste system of the largemouth bass, Micropterus
      salmoides, is highly selective to amino acids and is poorly responsive to
      trisodium citrate; however, IX taste responses to specific concentrations of L-
      and D-arginine and L-lysine but not L-proline were enhanced by citrate but not
      sodium ions. Binary mixtures of L-arginine (3 x 10(-4)M and 10(-3)M) or D
      arginine (10(-3)M) + trisodium citrate (10(-3)M; pH 7-9) resulted in enhanced
      taste activity, whereas binary mixtures of higher concentrations (10(-2)M and 10(
      1)M) of L- or D-arginine + 10(-3)M trisodium citrate were not significantly
      different from the response to the amino acid alone. Under continuous adaptation
      to 10(-3)M citrate, taste responses to L-arginine were also enhanced at the
      identical concentrations previously indicated, but responses to 10(-2)M and 10(
      1)M L-arginine were significantly suppressed. Under continuous adaptation to 10(
      2)M L-arginine, taste responses to 10(-2)M, 10(-1)M, and 10(0) M citrate were
      significantly enhanced. Cellular concentrations of both citrate and amino acids
      in prey of the carnivorous largemouth bass are sufficient for this taste
      enhancing effect to occur naturally during consummatory feeding behavior. Citrate
      acting as a calcium chelator is presented as a possible mechanism of action for
      the enhancement effect.

PMID- 10200194
TI  - Glutamate regulates IP3-type and CICR stores in the avian cochlear nucleus.
AB  - Neurons of the avian cochlear nucleus, nucleus magnocellularis (NM), are
      activated by glutamate released from auditory nerve terminals. If this
      stimulation is removed, the intracellular calcium ion concentration ([Ca2+]i) of
      NM neurons rises and rapid atrophic changes ensue. We have been investigating
      mechanisms that regulate [Ca2+]i in these neurons based on the hypothesis that
      loss of Ca2+ homeostasis causes the cascade of cellular changes that results in
      neuronal atrophy and death. In the present study, video-enhanced fluorometry was
      used to monitor changes in [Ca2+]i stimulated by agents that mobilize Ca2+ from
      intracellular stores and to study the modulation of these responses by glutamate.
      Homobromoibotenic acid (HBI) was used to stimulate inositol trisphosphate (IP3)
      sensitive stores, and caffeine was used to mobilize Ca2+ from Ca2+-induced Ca2+
      release (CICR) stores. We provide data indicating that Ca2+ responses
      attributable to IP3- and CICR-sensitive stores are inhibited by glutamate, acting
      via a metabotropic glutamate receptor (mGluR). We also show that activation of C
      kinase by a phorbol ester will reduce HBI-stimulated calcium responses. Although
      the protein kinase A accumulator, Sp-cAMPs, did not have an effect on HBI-induced
      responses. CICR-stimulated responses were not consistently attenuated by either
      the phorbol ester or the Sp-cAMPs. We have previously shown that glutamate
      attenuates voltage-dependent changes in [Ca2+]i. Coupled with the present
      findings, this suggests that in these neurons mGluRs serve to limit fluctuations
      in intracellular Ca2+ rather than increase [Ca2+]i. This system may play a role
      in protecting highly active neurons from calcium toxicity resulting in apoptosis.

PMID- 10200197
TI  - Contribution of single-channel properties to the time course and amplitude
      variance of quantal glycine currents recorded in rat motoneurons.
AB  - The amplitude of spontaneous, glycinergic miniature inhibitory postsynaptic
      currents (mIPSCs) recorded in hypoglossal motoneurons (HMs) in an in vitro brain
      stem slice preparation increased over the first 3 postnatal weeks, from 42 +/- 6
      pA in neonate (P0-3) to 77 +/- 11 pA in juvenile (P11-18) HMs. Additionally,
      mIPSC amplitude distributions were highly variable: CV 0.68 +/- 0.05 (means +/-
      SE) for neonates and 0.83 +/- 0.06 for juveniles. We wished to ascertain the
      contribution of glycine receptor (GlyR)-channel properties to this change in
      quantal amplitude and to the amplitude variability and time course of mIPSCs. To
      determine whether a postnatal increase in GlyR-channel conductance accounted for
      the postnatal change in quantal amplitude, the conductance of synaptic GlyR
      channels was determined by nonstationary variance analysis of mIPSCs. It was 48
      +/- 8 pS in neonate and 46 +/- 10 pS in juvenile HMs, suggesting that
      developmental changes in mIPSC amplitude do not result from a postnatal
      alteration of GlyR-channel conductance. Next we determined the open probability
      (Popen) of GlyR channels in outside-out patches excised from HMs to estimate the
      contribution of stochastic channel behavior to quantal amplitude variability.
      Brief (1 ms) pulses of glycine (1 mM) elicited patch currents that closely
      resembled mIPSCs. The GlyR channels' Popen, calculated by nonstationary variance
      analysis of these currents, was approximately 0.70 (0.66 +/- 0.09 in neonates and
      0.72 +/- 0.05 in juveniles). The decay rate of patch currents elicited by brief
      application of saturating concentrations of glycine (10 mM) increased
      postnatally, mimicking previously documented changes in mIPSC time course. Paired
      pulses of glycine (10 mM) were used to determine if rapid GlyR-channel
      desensitization contributed to either patch current time course or quantal
      amplitude variability. Because we did not observe any fast desensitization of
      patch currents, we believe that fast desensitization of GlyRs underlies neither
      phenomenon. From our analysis of glycinergic patch currents and mIPSCs, we draw
      three conclusions. First, channel deactivation is the primary determinant of
      glycinergic mIPSC time course, and postnatal changes in channel deactivation rate
      account for observed developmental changes in mIPSC decay rate. Second, because
      GlyR-channel Popen is high, differences in receptor number between synapses
      rather than stochastic channel behavior are likely to underlie the majority of
      quantal variability seen at glycinergic synapses throughout postnatal
      development. We estimate the number of GlyRs available at a synapse to be on
      average 27 in neonate neurons and 39 in juvenile neurons. Third, this change in
      the calculated number of GlyRs at each synapse may account for the postnatal
      increase in mIPSC amplitude.

PMID- 10200198
TI  - Opioidergic modulation of voltage-activated K+ currents in magnocellular neurons
      of the supraoptic nucleus in rat.
AB  - Opioidergic modulation plays an important role in the control of oxytocin and
      vasopressin release by magnocellular neurons (MCNs) in the supraoptic and
      paraventricular nuclei of the hypothalamus. We have used whole cell patch-clamp
      recording in acute slices of the supraoptic nucleus (SON) of the hypothalamus to
      study opioidergic modulation of voltage-dependent K+ currents in MCNs that are
      involved in release activity. The mu-receptor agonist D-Ala2, N-Me-Phe4, Gly5-ol
      enkephalin (DAMGO, 2 microM) affected K+ currents in 55% of magnocellular neurons
      recorded from. In these putative oxytocinergic cells, DAMGO increased the delayed
      rectifier current (IK(V)) amplitude by approximately 50% without significant
      effects on its activation kinetics. The transient A current (IA) was enhanced by
      DAMGO by approximately 36%. Its inactivation kinetic was accelerated slightly
      while the voltage dependence of steady-state inactivation was shifted by -6 mV to
      more negative potentials. All DAMGO effects were blocked by the preferential non
      kappa-opioid antagonist naloxone (10 microM). The kappa-opioid agonist trans-(+/
      )-3, 4-dichloro-N-methyl-N(2-[1-pyrrolidinyl]cyclohexyl)benzeneacetamide
      (U50,488; 10 microM) strongly suppressed IK(V) by approximately 57% and evoked a
      20-mV hyperpolarizing shift and an acceleration of activation in both, DAMGO
      sensitive and -insensitive putative vasopressinergic MCNs. U50,488 reduced IA by
      approximately 29% and tau of inactivation by -20% in DAMGO-sensitive cells. In
      contrast, in DAMGO-insensitive cells U50,488 increased IA by approximately 23%
      and strongly accelerated inactivation (tau -44%). The effects of U50,488 were
      suppressed by the selective kappa-receptor antagonist nor-binaltorphimine (5
      microM). We conclude that mu- and kappa-opioidergic inputs decrease and increase
      excitability of oxytocinergic MCNs, respectively, through modulation of voltage
      dependent K+ currents. In vasopressinergic MCNs, kappa-opioidergic inputs
      differentially modulate these K+ currents. The modulation of K+ currents is
      assumed to significantly contribute to opioidergic control of hormone release by
      MCNs within the supraoptic nucleus and from the axon terminals in the neural
      lobe.

PMID- 10200199
TI  - Somatostatin acts in CA1 and CA3 to reduce hippocampal epileptiform activity.
AB  - Although the peptide somatostatin (SST) has been speculated to function in
      temporal lobe epilepsy, its exact role is unclear, as in vivo studies have
      suggested both pro- and anticonvulsant properties. We have shown previously that
      SST has multiple inhibitory cellular actions in the CA1 region of the
      hippocampus, suggesting that in this region SST should have antiepileptic
      actions. To directly assess the effect of SST on epileptiform activity, we
      studied two in vitro models of epilepsy in the rat hippocampal slice preparation
      using extracellular and intracellular recording techniques. In one, GABA-mediated
      neurotransmission was inhibited by superfusion of the GABAA receptor antagonist
      bicuculline. In the second, we superfused Mg2+-free artificial cerebrospinal
      fluid to remove the Mg2+ block of the N-methyl-D-aspartate (NMDA) subtype of
      glutamate receptor. We show here that SST markedly reduces the intensity of
      evoked epileptiform afterdischarges and the frequency of spontaneous bursts in
      both CA1 and CA3. SST appears to act additively in the two regions to suppress
      the transmission of epileptiform events through the hippocampus. We further
      examined SST's actions in CA3 and found that SST dramatically reduced the
      frequency of paroxysmal depolarizing shifts (PDSs) recorded intracellularly in
      current clamp, as well as increasing the threshold for evoking "giant" excitatory
      postsynaptic currents (EPSCs), large polysynaptically mediated EPSCs that are the
      voltage-clamp correlate of PDSs. We also examined the actions of SST on
      pharmacologically isolated EPSCs generated at both mossy fiber (MF) and
      associational/commissural (A/C) synapses. SST appears to act specifically to
      reduce recurrent excitation between CA3 neurons because it depresses A/C- but not
      MF-evoked EPSCs. SST also increased paired-pulse facilitation of A/C EPSCs,
      suggesting a presynaptic site of action. Reciprocal activation of CA3 neurons
      through A/C fibers is critical for generation of epileptiform activity in
      hippocampus. Thus SST reduces feedforward excitation in rat hippocampus, acting
      to "brake" hyperexcitation. This is a function unique from that described for
      other hippocampal neuropeptides, which affect more standard neurotransmission.
      Our results suggest that SST receptors could be a unique, selective clinical
      target for treatment of limbic seizures.

PMID- 10200200
TI  - Ultrastructural analysis of ectopic synaptic boutons arising from peripherally
      regenerated primary afferent fibers.
AB  - The central axons of peripherally regenerated Abeta primary sensory neurons were
      impaled in the dorsal columns of alpha-chloralose-anesthetized cats 9-12 mo after
      axotomy. The adequate peripheral stimulus was determined, and the afferent fibers
      intracellularly stimulated while simultaneously recording the resulting cord
      dorsum potentials (CDPs). Fibers that successfully had reinnervated the skin
      responded to light tactile stimulation, and evoked CDPs that suggested dorsally
      located boutons were stained intracellularly with horseradish peroxidase (HRP).
      Two HRP-stained regenerated Abeta afferent fibers were recovered that supported
      large numbers of axon collaterals and swellings in laminae I, IIo, and IIi.
      Sections containing the ectopic collateral fibers and terminals in the
      superficial dorsal horn were embedded in plastic. Analyses of serial ultrathin
      sections revealed that ectopic projections from both regenerated fibers supported
      numerous synaptic boutons filled with clear round vesicles, a few large dense
      core vesicles (LDCVs) and several mitochondria (>3). All profiles examined in
      serial sections (19) formed one to three asymmetric axo-dendritic contacts.
      Unmyelinated portions of ectopic fibers giving rise to en passant and terminal
      boutons often contained numerous clear round vesicles. Several boutons (47%)
      received asymmetric contacts from axon terminals containing pleomorphic vesicles.
      These results strongly suggest that regenerated Abeta fibers activated by light
      tactile stimuli support functional connections in the superficial dorsal horn
      that have distinct ultrastructural features. In addition, the appearance of LDCVs
      suggests that primary sensory neurons are capable of changing their neurochemical
      phenotype.

PMID- 10200201
TI  - Recurrent mossy fiber pathway in rat dentate gyrus: synaptic currents evoked in
      presence and absence of seizure-induced growth.
AB  - A common feature of temporal lobe epilepsy and of animal models of epilepsy is
      the growth of hippocampal mossy fibers into the dentate molecular layer, where at
      least some of them innervate granule cells. Because the mossy fibers are axons of
      granule cells, the recurrent mossy fiber pathway provides monosynaptic excitatory
      feedback to these neurons that could facilitate seizure discharge. We used the
      pilocarpine model of temporal lobe epilepsy to study the synaptic responses
      evoked by activating this pathway. Whole cell patch-clamp recording demonstrated
      that antidromic stimulation of the mossy fibers evoked an excitatory postsynaptic
      current (EPSC) in approximately 74% of granule cells from rats that had survived
      >10 wk after pilocarpine-induced status epilepticus. Recurrent mossy fiber growth
      was demonstrated with the Timm stain in all instances. In contrast, antidromic
      stimulation of the mossy fibers evoked an EPSC in only 5% of granule cells
      studied 4-6 days after status epilepticus, before recurrent mossy fiber growth
      became detectable. Notably, antidromic mossy fiber stimulation also evoked an
      EPSC in many granule cells from control rats. Clusters of mossy fiber-like Timm
      staining normally were present in the inner third of the dentate molecular layer
      at the level of the hippocampal formation from which slices were prepared, and
      several considerations suggested that the recorded EPSCs depended mainly on
      activation of recurrent mossy fibers rather than associational fibers. In both
      status epilepticus and control groups, the antidromically evoked EPSC was
      glutamatergic and involved the activation of both AMPA/kainate and N-methyl-D
      aspartate (NMDA) receptors. EPSCs recorded in granule cells from rats with
      recurrent mossy fiber growth differed in three respects from those recorded in
      control granule cells: they were much more frequently evoked, a number of them
      were unusually large, and the NMDA component of the response was generally much
      more prominent. In contrast to the antidromically evoked EPSC, the EPSC evoked by
      stimulation of the perforant path appeared to be unaffected by a prior episode of
      status epilepticus. These results support the hypothesis that recurrent mossy
      fiber growth and synapse formation increases the excitatory drive to dentate
      granule cells and thus facilitates repetitive synchronous discharge. Activation
      of NMDA receptors in the recurrent pathway may contribute to seizure propagation
      under depolarizing conditions. Mossy fiber-granule cell synapses also are present
      in normal rats, where they may contribute to repetitive granule cell discharge in
      regions of the dentate gyrus where their numbers are significant.

PMID- 10200202
TI  - Possible novel mechanism for bitter taste mediated through cGMP.
AB  - Taste is the least understood among sensory systems, and bitter taste mechanisms
      pose a special challenge because they are elicited by a large variety of
      compounds. We studied bitter taste signal transduction with the quench-flow
      method and monitored the rapid kinetics of the second messenger guanosine 3',5'
      cyclic monophosphate (cGMP) production and degradation in mouse taste tissue. In
      response to the bitter stimulants, caffeine and theophylline but not strychnine
      or denatonium cGMP levels demonstrated a rapid and transient increase that peaked
      at 50 ms and gradually declined throughout the following 4.5 s. The theophylline-
      and caffeine-induced effect was rapid, transient, concentration dependent and
      gustatory tissue-specific. The effect could be partially suppressed in the
      presence of the soluble guanylyl cyclase (GC) inhibitor 10 microM ODQ and 30
      microM methylene blue but not 50 microM LY 83583 and boosted by nitric oxide
      donors 25 microM NOR-3 or 100 microM sodium nitroprusside. The proposed mechanism
      for this novel cGMP-mediated bitter taste signal transduction is cGMP production
      partially by the soluble GC and caffeine-induced inhibition of one or several
      phosphodiesterases.

PMID- 10200203
TI  - Discharge profiles of abducens, accessory abducens, and orbicularis oculi
      motoneurons during reflex and conditioned blinks in alert cats.
AB  - The discharge profiles of identified abducens, accessory abducens, and
      orbicularis oculi motoneurons have been recorded extra- and intracellularly in
      alert behaving cats during spontaneous, reflexively evoked, and classically
      conditioned eyelid responses. The movement of the upper lid and the
      electromyographic activity of the orbicularis oculi muscle also were recorded.
      Animals were conditioned by short, weak air puffs or 350-ms tones as conditioned
      stimuli (CS) and long, strong air puffs as unconditioned stimulus (US) using both
      trace and delayed conditioning paradigms. Motoneurons were identified by
      antidromic activation from their respective cranial nerves. Orbicularis oculi and
      accessory abducens motoneurons fired an early, double burst of action potentials
      (at 4-6 and 10-16 ms) in response to air puffs or to the electrical stimulation
      of the supraorbital nerve. Orbicularis oculi, but not accessory abducens,
      motoneurons fired in response to flash and tone presentations. Only 10-15% of
      recorded abducens motoneurons fired a late, weak burst after air puff,
      supraorbital nerve, and flash stimulations. Spontaneous fasciculations of the
      orbicularis oculi muscle and the activity of single orbicularis oculi motoneurons
      that generated them also were recorded. The activation of orbicularis oculi
      motoneurons during the acquisition of classically conditioned eyelid responses
      happened in a gradual, sequential manner. Initially, some putative excitatory
      synaptic potentials were observed in the time window corresponding to the CS-US
      interval; by the second to the fourth conditioning session, some isolated action
      potentials appeared that increased in number until some small movements were
      noticed in eyelid position traces. No accessory abducens motoneuron fired and no
      abducens motoneuron modified their discharge rate for conditioned eyelid
      responses. The firing of orbicularis oculi motoneurons was related linearly to
      lid velocity during reflex blinks but to lid position during conditioned
      responses, a fact indicating the different neural origin and coding of both types
      of motor commands. The power spectra of both reflex and conditioned lid responses
      showed a dominant peak at approximately 20 Hz. The wavy appearance of both reflex
      and conditioned eyelid responses was clearly the result of the high phasic
      activity of orbicularis oculi motor units. Orbicularis oculi motoneuron membrane
      potentials oscillated at approximately 20 Hz after supraorbital nerve stimulation
      and during other reflex and conditioned eyelid movements. The oscillation seemed
      to be the result of both intrinsic (spike afterhyperpolarization lasting
      approximately 50 ms, and late depolarizations) and extrinsic properties of the
      motoneuronal pool and of the circuits involved in eye blinks.

PMID- 10200204
TI  - Impulse encoding across the dendritic morphologies of retinal ganglion cells.
AB  - Nerve impulse entrainment and other excitation and passive phenomena are analyzed
      for a morphologically diverse and exhaustive data set (n = 57) of realistic (3
      dimensional computer traced) soma-dendritic tree structures of ganglion cells in
      the tiger salamander (Ambystoma tigrinum) retina. The neurons, including axon and
      an anatomically specialized thin axonal segment that is observed in every
      ganglion cell, were supplied with five voltage- or ligand-gated ion channels
      (plus leakage), which were distributed in accordance with those found in a recent
      study that employed an equivalent dendritic cylinder. A wide variety of impulse
      entrainment responses was observed, including regular low-frequency firing,
      impulse doublets, and more complex patterns involving impulse propagation
      failures (or aborted spikes) within the encoder region, all of which have been
      observed experimentally. The impulse-frequency response curves of the cells fell
      into three groups called FAST, MEDIUM, and SLOW in approximate proportion as seen
      experimentally. In addition to these, a new group was found among the traced
      cells that exhibited an impulse-frequency response twice that of the FAST
      category. The total amount of soma-dendritic surface area exhibited by a given
      cell is decisive in determining its electrophysiological classification. On the
      other hand, we found only a weak correlation between the electrophysiological
      group and the morphological classification of a given cell, which is based on the
      complexity of dendritic branching and the physical reach or "receptive field"
      area of the cell. Dendritic morphology determines discharge patterns to dendritic
      (synaptic) stimulation. Orthodromic impulses can be initiated on the axon
      hillock, the thin axonal segment, the soma, or even the proximal axon beyond the
      thin segment, depending on stimulus magnitude, soma-dendritic membrane area,
      channel distribution, and state within the repetitive impulse cycle. Although a
      sufficiently high dendritic Na-channel density can lead to dendritic impulse
      initiation, this does not occur with our "standard" channel densities and is not
      seen experimentally. Even so, impulses initiated elsewhere do invade all except
      very thin dendritic processes. Impulse-encoding irregularities increase when
      channel conductances are reduced in the encoder region, and the F/I properties of
      the cells are a strong function of the calcium- and Ca-activated K-channel
      densities. Use of equivalent dendritic cylinders requires more soma-dendritic
      surface area than real dendritic trees, and the source of the discrepancy is
      discussed.

PMID- 10200205
TI  - Calcium channels involved in synaptic transmission from reticulospinal axons in
      lamprey.
AB  - The pharmacology of calcium channels involved in glutamatergic synaptic
      transmission from reticulospinal axons in the lamprey spinal cord was analyzed
      with specific agonists and antagonists of different high-voltage activated
      calcium channels. The N-type calcium channel blocker omega-conotoxin GVIA (omega
      CgTx) induced a large decrease of the amplitude of reticulospinal-evoked
      excitatory postsynaptic potentials (EPSPs). The P/Q-type calcium channel blocker
      omega-agatoxin IVA (omega-Aga) also reduced the amplitude of the reticulospinal
      EPSPs, but to a lesser extent than omega-CgTx. The dihydropyridine agonist Bay K
      and antagonist nimodipine had no effect on the amplitude of the reticulospinal
      EPSP. Combined application of omega-CgTx and omega-Aga strongly decreased the
      amplitude the EPSPs but was never able to completely block them, indicating that
      calcium channels insensitive to these toxins (R-type) are also involved in
      synaptic transmission from reticulospinal axons. We have previously shown that
      the group III metabotropic glutamate receptor agonist L(+)-2-amino-4
      phosphonobutyric acid (L-AP4) mediates presynaptic inhibition at the
      reticulospinal synapse. To test if this presynaptic effect is mediated through
      inhibition of calcium influx, the effect of L-AP4 on reticulospinal transmission
      was tested before and after blockade of N-type channels, which contribute
      predominantly to transmitter release at this synapse. Blocking the N-type
      channels with omega-CgTx did not prevent inhibition of reticulospinal synaptic
      transmission by L-AP4. In addition, L-AP4 had no affect on the calcium current
      recorded in the somata of reticulospinal neurons or on the calcium component of
      action potentials in reticulospinal axons. These results show that synaptic
      transmission from reticulospinal axons in the lamprey is mediated by calcium
      influx through N-, P/Q- and R-type channels, with N-type channels playing the
      major role. Furthermore, presynaptic inhibition of reticulospinal transmission by
      L-AP4 appears not to be mediated through inhibition of presynaptic calcium
      channels.

PMID- 10200206
TI  - Control of fingertip forces in multidigit manipulation.
AB  - Previous studies of control of fingertip forces in skilled manipulation have
      focused on tasks involving two digits, typically the thumb and index finger. Here
      we examine control of fingertip actions in a multidigit task in which subjects
      lifted an object using unimanual and bimanual grasps engaging the tips of the
      thumb and two fingers. The grasps resembled those used when lifting a cylindrical
      object from above; the two fingers were some 4.25 cm apart and the thumb was
      approximately 5.54 cm from either finger. The three-dimensional forces and
      torques applied by each digit and the digit contact positions were measured along
      with the position and orientation of the object. The vertical forces applied
      tangential to the grasp surfaces to lift the object were synchronized across the
      digits, and the contribution by each digit to the total vertical force reflected
      intrinsic object properties (geometric relationship between the object's center
      of mass and the grasped surfaces). Subjects often applied small torques
      tangential to the grasped surfaces even though the object could have been lifted
      without such torques. The normal forces generated by each digit increased in
      parallel with the local tangential load (force and torque), providing an adequate
      safety margin against slips at each digit. In the present task, the orientations
      of the force vectors applied by the separate digits were not fully constrained
      and therefore the motor controller had to choose from a number of possible
      solutions. Our findings suggest that subjects attempt to minimize (or at least
      reduce) fingertip forces while at the same time ensure that grasp stability is
      preserved. Subjects also avoid horizontal tangential forces, even at a small cost
      in total force. Moreover, there were subtle actions exerted by the digits that
      included changes in the distribution of vertical forces across digits and slight
      object tilt. It is not clear to what extent the brain explicitly controlled these
      actions, but they could serve, for instance, to keep tangential torques small and
      to compensate for variations in digit contact positions. In conclusion, we have
      shown that when lifting an object with a three-digit grip, the coordination of
      fingertip forces, in many respects, matches what has been documented previously
      for two-digit grasping. At the same time, our study reveals novel aspects of
      force control that emerge only in multidigit manipulative tasks.

PMID- 10200207
TI  - Force-frequency and fatigue properties of motor units in muscles that control
      digits of the human hand.
AB  - Modulation of motor unit activation rate is a fundamental process by which the
      mammalian nervous system encodes muscle force. To identify how rate coding of
      force may change as a consequence of fatigue, intraneural microstimulation of
      motor axons was used to elicit twitch and force-frequency responses before and
      after 2 min of intermittent stimulation (40-Hz train for 330 ms, 1 train/s) in
      single motor units of human long finger flexor muscles and intrinsic hand
      muscles. Before fatigue, two groups of units could be distinguished based on the
      stimulus frequency needed to elicit half-maximal force; group 1 (n = 8) required
      9.1 +/- 0.5 Hz (means +/- SD), and group 2 (n = 5) required 15.5 +/- 1.1 Hz.
      Twitch contraction times were significantly different between these two groups
      (group 1 = 66. 5 ms; group 2 = 45.9 ms). Overall 18% of the units were fatigue
      resistant [fatigue index (FI) > 0.75], 64% had intermediate fatigue sensitivity
      (0.25 </= FI </= 0.75), and 18% were fatigable (FI < 0. 25). However,
      fatigability and tetanic force were not significantly different among groups.
      Therefore unlike findings in some other mammals, fast-contracting motor units
      were neither stronger nor more susceptible to fatigue than slowly contracting
      units. Fatigue, however, was found to be greatest in those units that initially
      exerted the largest forces. Despite significant slowing of contractile responses,
      fatigue caused the force-frequency relation to become displaced toward higher
      frequencies (44 +/- 41% increase in frequency for half-maximal force). Moreover,
      the greatest shift in the force-frequency relation occurred among those units
      exhibiting the largest force loss. A selective deficit in force at low
      frequencies of stimulation persisted for several minutes after the fatigue task.
      Overall, these findings suggest that with fatigue higher activation rates must be
      delivered to motor units to maintain the same relative level of force. Questions
      regarding classification of motor units and possible mechanisms by which fatigue
      related slowing might coexist with a shift in the force-frequency curve toward
      higher frequencies are discussed.

PMID- 10200208
TI  - Neuropeptide-mediated facilitation and inhibition of sensory inputs and spinal
      cord reflexes in the lamprey.
AB  - The effects of neuromodulators present in the dorsal horn [tachykinins,
      neuropeptide Y (NPY), bombesin, and GABAB agonists] were studied on reflex
      responses evoked by cutaneous stimulation in the lamprey. Reflex responses were
      elicited in an isolated spinal cord preparation by electrical stimulation of the
      attached tail fin. To be able to separate modulator-induced effects at the
      sensory level from that at the motor or premotor level, the spinal cord was
      separated into three pools with Vaseline barriers. The caudal pool contained the
      tail fin. Neuromodulators were added to this pool to modulate sensory inputs
      evoked by tail fin stimulation. The middle pool contained high divalent cation or
      low calcium Ringer to block polysynaptic transmission and thus limit the input to
      the rostral pool to that from ascending axons that project through the middle
      pool. Ascending inputs and reflex responses were monitored by making
      intracellular recordings from motor neurons and extracellular recordings from
      ventral roots in the rostral pool. The tachykinin neuropeptide substance P, which
      has previously been shown to potentiate sensory input at the cellular and
      synaptic levels, facilitated tail fin-evoked synaptic inputs to neurons in the
      rostral pool and concentration dependently facilitated rostral ventral root
      activity. Substance P also facilitated the modulatory effects of tail fin
      stimulation on ongoing locomotor activity in the rostral pool. In contrast, NPY
      and the GABAB receptor agonist baclofen, both of which have presynaptic
      inhibitory effects on sensory afferents, reduced the strength of ascending inputs
      and rostral ventral root responses. We also examined the effects of the
      neuropeptide bombesin, which is present in sensory axons, at the cellular,
      synaptic, and reflex levels. As with substance P, bombesin increased tail fin
      stimulation-evoked inputs and ventral root responses in the rostral pool. These
      effects were associated with the increased excitability of slowly adapting
      mechanosensory neurons and the potentiation of glutamatergic synaptic inputs to
      spinobulbar neurons. These results show the possible behavioral relevance of
      neuropeptide-mediated modulation of sensory inputs at the cellular and synaptic
      levels. Given that the types and locations of neuropeptides in the dorsal spinal
      cord of the lamprey show strong homologies to that of higher vertebrates, these
      results are presumably relevant to other vertebrate systems.

PMID- 10200209
TI  - Long-term potentiation in the dentate gyrus is not linked to increased
      extracellular glutamate concentration.
AB  - Long-term potentiation (LTP) of excitatory transmission is a likely candidate for
      the encoding and storage of information in the mammalian brain. There is a
      general agreement that LTP involves an increase in synaptic strength, but the
      mechanisms underlying this persistent change are unclear and controversial.
      Synaptic efficacy may be enhanced because more transmitter glutamate is released
      or because postsynaptic responsiveness increases or both. The purpose of this
      study was to examine whether increased extracellular glutamate concentration was
      associated with the robust and well-characterized LTP that can be induced in the
      rat dentate gyrus. To favor the detection of any putative change in extracellular
      glutamate associated with LTP, our experimental strategy included the following
      features. 1) Two separate series of experiments were carried out with animals
      under pentobarbital or urethan anesthesia; 2) changes in extracellular
      concentration of glutamate were monitored continuously by microdialysis coupled
      to enzyme amperometry; and 3) dialysate glutamate levels and changes in the slope
      of excitatory postsynaptic potential evoked by activation of the perforant path
      were recorded precisely at the same site. Tetanic stimulation of the perforant
      path increased persistently test-evoked responses in the dentate gyrus (by 19 and
      14% in barbiturate and urethan group, respectively), but there was no glutamate
      change either during or after LTP induction and no indication of increased
      glutamate efflux when low-frequency stimulation was applied. The results do not
      rule out a possible contribution of enhanced glutamate exocytosis to LTP
      induction and/or maintenance because such a presynaptic change may not be
      detectable extracellularly. However, our findings and other data supporting the
      notion that neurotransmitter glutamate may hardly leak out of the synaptic cleft
      conflict with the hypothesis that LTP could also involve a broad synaptic
      spillover of glutamate.

PMID- 10200210
TI  - IA in Kenyon cells of the mushroom body of honeybees resembles shaker currents:
      kinetics, modulation by K+, and simulation.
AB  - Cultured Kenyon cells from the mushroom body of the honeybee, Apis mellifera,
      show a voltage-gated, fast transient K+ current that is sensitive to 4
      aminopyridine, an A current. The kinetic properties of this A current and its
      modulation by extracellular K+ ions were investigated in vitro with the whole
      cell patch-clamp technique. The A current was isolated from other voltage-gated
      currents either pharmacologically or with suitable voltage-clamp protocols.
      Hodgkin- and Huxley-style mathematical equations were used for the description of
      this current and for the simulation of action potentials in a Kenyon cell model.
      Activation and inactivation of the A current are fast and voltage dependent with
      time constants of 0.4 +/- 0.1 ms (means +/- SE) at +45 mV and 3.0 +/- 1.6 ms at
      +45 mV, respectively. The pronounced voltage dependence of the inactivation
      kinetics indicates that at least a part of this current of the honeybee Kenyon
      cells is a shaker-like current. Deactivation and recovery from inactivation also
      show voltage dependency. The time constant of deactivation has a value of 0.4 +/-
      0.1 ms at -75 mV. Recovery from inactivation needs a double-exponential function
      to be fitted adequately; the resulting time constants are 18 +/- 3.1 ms for the
      fast and 745 +/- 107 ms for the slow process at -75 mV. Half-maximal activation
      of the A current occurs at -0.7 +/- 2.9 mV, and half-maximal inactivation occurs
      at -54.7 +/- 2.4 mV. An increase in the extracellular K+ concentration increases
      the conductance and accelerates the recovery from inactivation of the A current,
      affecting the slow but not the fast time constant. With respect to these
      modulations the current under investigation resembles some of the shaker-like
      currents. The data of the A current were incorporated into a reduced
      computational model of the voltage-gated currents of Kenyon cells. In addition,
      the model contained a delayed rectifier K+ current, a Na+ current, and a leakage
      current. The model is able to generate an action potential on current injection.
      The model predicts that the A current causes repolarization of the action
      potential but not a delay in the initiation of the action potential. It further
      predicts that the activation of the delayed rectifier K+ current is too slow to
      contribute markedly to repolarization during a single action potential. Because
      of its fast activation, the A current reduces the amplitude of the net
      depolarizing current and thus reduces the peak amplitude and the duration of the
      action potential.

PMID- 10200211
TI  - Three-dimensional eye-head coordination during gaze saccades in the primate.
AB  - The purpose of this investigation was to describe the neural constraints on three
      dimensional (3-D) orientations of the eye in space (Es), head in space (Hs), and
      eye in head (Eh) during visual fixations in the monkey and the control strategies
      used to implement these constraints during head-free gaze saccades. Dual scleral
      search coil signals were used to compute 3-D orientation quaternions, two
      dimensional (2-D) direction vectors, and 3-D angular velocity vectors for both
      the eye and head in three monkeys during the following visual tasks: radial
      to/from center, repetitive horizontal, nonrepetitive oblique, random (wide 2-D
      range), and random with pin-hole goggles. Although 2-D gaze direction (of Es) was
      controlled more tightly than the contributing 2-D Hs and Eh components, the
      torsional standard deviation of Es was greater (mean 3.55 degrees ) than Hs (3.10
      degrees ), which in turn was greater than Eh (1.87 degrees ) during random
      fixations. Thus the 3-D Es range appeared to be the byproduct of Hs and Eh
      constraints, resulting in a pseudoplanar Es range that was twisted (in orthogonal
      coordinates) like the zero torsion range of Fick coordinates. The Hs fixation
      range was similarly Fick-like, whereas the Eh fixation range was quasiplanar. The
      latter Eh range was maintained through exquisite saccade/slow phase coordination,
      i.e., during each head movement, multiple anticipatory saccades drove the eye
      torsionally out of the planar range such that subsequent slow phases drove the
      eye back toward the fixation range. The Fick-like Hs constraint was maintained by
      the following strategies: first, during purely vertical/horizontal movements, the
      head rotated about constantly oriented axes that closely resembled physical Fick
      gimbals, i.e., about head-fixed horizontal axes and space-fixed vertical axes,
      respectively (although in 1 animal, the latter constraint was relaxed during
      repetitive horizontal movements, allowing for trajectory optimization). However,
      during large oblique movements, head orientation made transient but dramatic
      departures from the zero-torsion Fick surface, taking the shortest path between
      two torsionally eccentric fixation points on the surface. Moreover, in the pin
      hole goggle task, the head-orientation range flattened significantly, suggesting
      a task-dependent default strategy similar to Listing's law. These and previous
      observations suggest two quasi-independent brain stem circuits: an oculomotor 2-D
      to 3-D transformation that coordinates anticipatory saccades with slow phases to
      uphold Listing's law, and a flexible "Fick operator" that selects head motor
      error; both nested within a dynamic gaze feedback loop.

PMID- 10200212
TI  - Effect of spatial attention on the responses of area MT neurons.
AB  - This study examines the influence of spatial attention on the responses of
      neurons in the middle temporal visual area (MT or V5) of extrastriate cortex. Two
      monkeys were trained to perform a direction-discrimination task. On each trial,
      two apertures of random-dot stimuli appeared simultaneously at two spatially
      separated locations; the monkeys were required to discriminate the direction of
      stimulus motion at one location while ignoring the stimulus at the other
      location. After extensive training, we recorded the responses of MT neurons in
      two configurations: 1) Both apertures placed "within" the neuron's receptive
      field (RF) and 2) one aperture covering the RF while the other was presented at a
      "remote" location. For each unit we compared the responses to identical stimulus
      displays when the monkey was instructed to attend to one or the other aperture.
      The responses of MT neurons were 8.7% stronger, on average, when the monkey
      attended to the spatial location that contained motion in the "preferred"
      direction. Attentional effects were equal, on average, in the within RF and
      remote configurations. The attentional modulations began approximately 300 ms
      after stimulus onset, gradually increased throughout the trial, and peaked near
      stimulus offset. An analysis of the neuronal responses on error trials suggests
      that the monkeys failed to attend to the appropriate spatial location on these
      trials. The relatively weak attentional effects that we observed contrast
      strikingly with recent results of Treue and Maunsell, who demonstrated very
      strong attentional modulations (median effect >80%) in MT in a task that shares
      many features with ours. Our results suggest that spatial attention alone is not
      sufficient to induce strong attentional effects in MT even when two competing
      motion stimuli appear within the RF of the recorded neuron. The difference
      between our results and those of Treue and Maunsell suggests that the magnitude
      of the attentional effects in MT may depend critically on how attention is
      directed to a particular stimulus and on the precise demands of the task.

PMID- 10200213
TI  - Mechanism of anesthesia revealed by shunting actions of isoflurane on
      thalamocortical neurons.
AB  - By using thalamic brain slices from juvenile rats and the whole cell recording
      technique, we determined the effects of aqueous applications of the anesthetic
      isoflurane (IFL) on tonic and burst firing activities of ventrobasal relay
      neurons. At concentrations equivalent to those used for in vivo anesthesia, IFL
      induced a hyperpolarization and increased membrane conductance in a reversible
      and concentration-dependent manner (ionic mechanism detailed in companion paper).
      The increased conductance short-circuited the effectiveness of depolarizing
      pulses and was the main cause for inhibition of tonic firing of action
      potentials. Despite the IFL-induced hyperpolarization, which theoretically should
      have promoted bursting, the shunt blocked the low-threshold Ca2+ spike (LTS) and
      associated burst firing of action potentials as well as the high-threshold Ca2+
      spike (HTS). Increasing the amplitude of either the depolarizing test pulse or
      hyperpolarizing prepulse or increasing the duration of the hyperpolarizing
      prepulse partially reversed the blockade of the LTS burst. In voltage-clamp
      experiments on the T-type Ca2+ current, which produces the LTS, IFL decreased the
      spatial distribution of imposed voltages and hence impaired the activation of
      spatially distant T channels. Although IFL may have increased a dendritic leak
      conductance or decreased dendritic Ca2+ currents, the somatic shunt appeared to
      block initiation of the LTS and HTS as well as their electrotonic propogation to
      the axon hillock. In summary, IFL hyperpolarized thalamocortical neurons and
      shunted voltage-dependent Na+ and Ca2+ currents. Considering the importance of
      the thalamus in relaying different sensory modalities (i.e., somatosensation,
      audition, and vision) and motor information as well as the corticothalamocortical
      loops in mediating consciousness, the shunted firing activities of
      thalamocortical neurons would be instrumental for the production of anesthesia in
      vivo.

PMID- 10200214
TI  - Ionic mechanism of isoflurane's actions on thalamocortical neurons.
AB  - We studied the actions of isoflurane (IFL) applied in aqueous solutions on
      ventrobasal neurons from thalamic brain slices of juvenile rats. By using the
      whole cell, patch-clamp method with current- and voltage-clamp recording
      techniques, we found that IFL increased a noninactivating membrane conductance in
      a concentration-dependent reversible manner. In an eightfold concentration range
      that extended into equivalent in vivo lethal concentrations, IFL did not produce
      a maximal effect on the conductance; this is consistent with a nonreceptor
      mediated mechanism of action. TTX eliminated action potential activity but did
      not alter IFL effects. The effects on the membrane potential and current induced
      by IFL were voltage independent but depended on the external [K+], reversing near
      the equilibrium potential for K+. External Ba2+ or internal Cs+ applications,
      which block K+ channels, suppressed the conductance increase caused by IFL.
      External applications of the Ca2+ channel blockers Co2+ or Cd2+ or internal
      application of the Ca2+ chelator 1,2-bis-(2-aminophenoxy)-ethane-N,N, N',N'
      tetraacetic acid did not prevent the effects of IFL, implying little involvement
      of Ca2+-dependent K+ currents. A contribution of inwardly rectifying K+ channels
      to the increased steady-state conductance seemed unlikely because IFL decreased
      inward rectification. An involvement of ATP-mediated K+ channels also was
      unlikely because application of the ATP-mediated K+ channel blocker glibenclamide
      (1-80 microM) did not prevent IFL's actions. In contrast to spiking cells, IFL
      depolarized presumed glial cells, consistent with an efflux of K+ from
      thalamocortical neurons. The results imply that a leak K+ channel mediated the
      IFL-induced increase in postsynaptic membrane conductance in thalamic relay
      neurons. Thus a single nonreceptor-mediated mechanism of IFL action was
      responsible for the hyperpolarization and conductance shunt of voltage-dependent
      Na+ and Ca2+ spikes, as reported in the preceding paper. Although anesthetics
      influence various neurological systems, an enhanced K+ leak generalized in
      thalamocortical neurons alone could account for anesthesia in vivo.

PMID- 10200215
TI  - Analysis of multiquantal transmitter release from single cultured cortical neuron
      terminals.
AB  - Application of single synapse recording methods indicates that the amplitude of
      postsynaptic responses of single CNS synapses can vary greatly among repeated
      stimuli. To determine whether this observation could be attributed to synapses
      releasing a variable number of transmitter quanta, we assessed the prevalence of
      multiquantal transmitter release in primary cultures of cortical neurons with the
      action potential (AP)-dependent presynaptic turnover of the styryl dye FM1-43 (,;
      ). It was assumed that if a high proportion of vesicles within a terminal were
      loaded with FM1-43 the amount of dye released per stimulus would be proportional
      to the number of quanta released and/or the probability of release at a terminal.
      To rule out differences in the amount of release (between terminals) caused by
      release probability or incomplete loading of terminals, conditions were chosen to
      maximize both release probability and terminal loading. Three-dimensional
      reconstruction of terminals was employed to ensure that bouton fluorescence was
      accurately measured. Analysis of the relationship between the loading of
      terminals and release indicated that presumed larger terminals (>FM1-43 uptake)
      release a greater amount of dye per stimulus than smaller terminals, suggesting
      multiquantal release. The distribution of release amounts across terminals was
      significantly skewed toward higher values, with 13-17% of synaptic terminals
      apparently releasing multiple quanta per AP. In conclusion, our data suggest that
      most synaptic terminals release a relatively constant amount of transmitter per
      stimulus; however, a subset of terminals releases amounts of FM1-43 that are
      greater than that expected from a unimodal release process.

PMID- 10200216
TI  - FMRFamide-activated Ca2+ channels in Lymnaea heart cells are modulated by
      "SEEPLY," a neuropeptide encoded on the same gene.
AB  - The cell-attached, patch-clamp technique was used to investigate the modulatory
      role of the neuropeptide SEQPDVDDYLRDVVLQSEEPLY ("SEEPLY") on FMRFamide-activated
      Ca2+ channels in isolated Lymnaea heart ventricular cells. Both SEEPLY and
      FMRFamide are encoded on the same neuropeptide gene and are coexpressed in a pair
      of excitatory motor neurons that innervate the heart. FMRFamide applied alone was
      capable of significantly increasing the P(open) time of a Ca2+ channel in
      isolated heart muscle cells. However, SEEPLY applied alone did not significantly
      alter the basal level of Ca2+ channel activity in the same cells. Repeated
      applications of FMRFamide (15 s every min) resulted in a progressive reduction in
      the number of Ca2+ channel openings and the overall P(open) time of the channel.
      The fifth successive 15-s application of FMRFamide failed to cause the Ca2+
      channels to open in the majority of cells tested. When FMRFamide and SEEPLY were
      repeatedly applied together (2-min applications every 4 min) the FMRFamide
      activated Ca2+ channels continued to respond after the fifth application of the
      two peptides. Indeed channel activity was seen to continue after repeated 2-min
      applications of FMRFamide and SEEPLY for as long as the patch lasted (</=60 min).
      As well as preventing the loss of response to FMRFamide, SEEPLY was also capable
      of both up- and down-regulating the response of the Ca2+ channel to FMRFamide.
      The direction of the response depended on the P(open) time of the channel before
      the application of SEEPLY. When the P(open) time for the FMRFamide-activated
      channel was initially 0.004 +/- 0.002 (means +/- SE), subsequent perfusion with a
      mixture of FMRFamide and SEEPLY produced a statistically significant increase in
      Ca2+ channel activity (13 cells). In two cells where no channel activity was
      observed in response to an initial application of FMRFamide, superfusing the
      heart cells with a mixture of FMRFamide and SEEPLY induced openings of the Ca2+
      channel. When the P(open) time of FMRFamide-induced Ca2+ channel openings was
      0.058 +/- 0.017 the subsequent application of a mixture of SEEPLY and FMRFamide
      caused a statistically significant decrease in Ca2+ channel activity (8 cells).
      As up- and down-regulation of FMRFamide-activated Ca2+ channel openings by SEEPLY
      were observed in the same cells (8 cells), this suggested that corelease of the
      two peptides might act together to regulate the level of Ca2+ channel activity
      within a defined range.

PMID- 10200217
TI  - Effect of reversible inactivation of macaque lateral intraparietal area on visual
      and memory saccades.
AB  - Previous studies from our laboratory identified a parietal eye field in the
      primate lateral intraparietal sulcus, the lateral intraparietal area (area LIP).
      Here we further explore the role of area LIP in processing saccadic eye movements
      by observing the effects of reversible inactivation of this area. One to 2 microl
      of muscimol (8 mg/ml) were injected at locations where saccade-related activities
      were recorded for each lesion experiment. After the muscimol injection we
      observed in two macaque monkeys consistent effects on both the metrics and
      dynamics of saccadic eye movements at many injection sites. These effects usually
      took place within 10-30 min and disappeared after 5-6 h in most cases and
      certainly when tested the next day. After muscimol injection memory saccades
      directed toward the contralesional and upper space became hypometric, and in one
      monkey those to the ipsilesional space were slightly but significantly
      hypermetric. In some cases, the scatter of the end points of memory saccades was
      also increased. On the other hand, the metrics of visual saccades remained
      relatively intact. Latency for both visual and memory saccades toward the
      contralesional space was increased and in many cases displayed a higher variance
      after muscimol lesion. At many injection sites we also observed an increase of
      latency for visual and memory saccades toward the upper space. The peak
      velocities for memory saccades toward the contralesional space were decreased
      after muscimol injection. The peak velocities of visual saccades were not
      significantly different from those of the controls. The duration of saccadic eye
      movements either to the ipsilesional or contralesional space remained relatively
      the same for both visual and memory saccades. Overall these results demonstrated
      that we were able to selectively inactivate area LIP and observe effects on
      saccadic eye movements. Together with our previous recording studies these
      results futher support the view that area LIP plays a direct role in processing
      incoming sensory information to program saccadic eye movements. The results are
      consistent with our unit recording data and microstimulation studies, which
      suggest that area LIP represents contralateral space and also has a bias for the
      upper visual field.

PMID- 10200218
TI  - Modulation of N-type Ca2+ channels by intracellular pH in chick sensory neurons.
AB  - Both physiological and pathological neuronal events, many of which elevate
      intracellular [Ca2+], can produce changes in intracellular pH of between 0.15 and
      0.5 U, between pH 7.4 and 6.8. N-type Ca2+ channels, which are intimately
      involved in exocytosis and other excitable cell processes, are sensitive to
      intracellular pH changes. However, the pH range over which N-type Ca2+ channels
      are sensitive, and the sensitivity of N-type Ca2+ channels to small changes in
      intracellular pH, are unknown. We studied the influence of intracellular pH
      changes on N-type calcium channel currents in dorsal root ganglion neurons,
      acutely isolated from 14-day-old chick embryos. Intracellular pH was monitored in
      patch-clamp recordings with the fluorescent dye, BCECF, and manipulated in both
      the acidic and basic direction by extracellular application of NH4+ in the
      presence and absence of intracellular NH4+. Changes in intracellular pH between
      6.6 and 7.5 produced a graded change in Ca2+ current magnitude with no apparent
      shift in activation potential. Intracellular acidification from pH 7.3 to 7.0
      reversibly inhibited Ca2+ currents by 40%. Acidification from pH 7.3 to pH 6.6
      reversibly inhibited Ca2+ currents by 65%. Alkalinization from pH 7.3 to 7.5
      potentiated Ca2+ currents by approximately 40%. Channels were sensitive to pHi
      changes with high intracellular concentrations of the Ca2+ chelator, bis-(o
      aminophenoxy)-N,N,N',N'-tetraacetic acid, which indicates that the effects of pHi
      did not involve a Ca2+-dependent mechanism. These data indicate that N-type Ca2+
      channel currents are extremely sensitive to small changes in pHi in the range
      produced by both physiological and pathological events. Furthermore, these data
      suggest that modulation of N-type Ca2+ channels by pHi may play an important role
      in physiological processes that produce small changes in pHi and a protective
      role in pathological mechanisms that produce larger changes in pHi.

PMID- 10200219
TI  - Selective inhibition of transient K+ current by La3+ in crab peptide-secretory
      neurons.
AB  - Although divalent cations and lanthides are well-known inhibitors of voltage
      dependent Ca2+ currents (ICa), their ability to selectively inhibit a voltage
      gated K+ current is less widely documented. We report that La3+ inhibits the
      transient K+ current (IA) of crab (Cardisoma carnifex) neurosecretory cells at
      ED50 approximately 5 microM, similar to that blocking ICa, without effecting the
      delayed rectifier K+ current (IK). Neurons were dissociated from the major
      crustacean neuroendocrine system, the X-organ-sinus gland, plated in defined
      medium, and recorded by whole cell patch clamp after 1-2 days in culture. The
      bath saline included 0.5 microM TTX and 0.5 mM CdCl2 to eliminate inward
      currents. Responses to depolarizing steps from a holding potential of -40 mV
      represented primarily IK. They were unchanged by La3+ up to 500 microM. Currents
      from -80 mV in the presence of 20 mM TEA were shown to represent primarily IA.
      La3+ (with TEA) reduced IA and maximum conductance (GA) by approximately 10% for
      1 microM and another 10% each in 10 and 100 microM La3+. Normalized GA-V curves
      were well fit with a single Boltzmann function, with V1/2 +4 mV and slope 15 mV
      in control; V1/2 was successively approximately 15 mV depolarized and slope
      increased approximately 2 mV for each of these La3+ concentrations. Cd2+ (1 mM),
      Zn2+ (200 microM), and Pb2+ (100 microM) or removal of saline Mg2+ (26 mM) had
      little or no effect on IA. Steady-state inactivation showed similar right shifts
      (from V1/2 -39 mV) and slope increases (from 2.5 mV) in 10 and 100 microM La3+.
      Time to peak IA was slowed in 10 and 100 microM La3+, whereas curves of
      normalized time constants of initial decay from peak IA versus Vc were right
      shifted successively approximately 15 mV for the three La3+ concentrations. The
      observations were fitted by a Woodhull-type model postulating a La3+-selective
      site that lies 0.26-0.34 of the distance across the membrane electric field, and
      both block of K+ movement and interaction with voltage-gating mechanisms; block
      can be relieved by depolarization and/or outward current. The observation of
      selective inhibition of IA by micromolar La3+ raises concerns about its use in
      studies of ICa to evaluate contamination by outward current.

PMID- 10200221
TI  - Membrane dysfunction induced by in vitro ischemia in immature rat hippocampal CA1
      neurons.
AB  - We investigated differences between immature and mature hippocampal neurons in
      their response to deprivation of oxygen and glucose (in vitro ischemia), using
      intracellular recording techniques from CA1 pyramidal neurons in rat brain
      slices. The membrane was more depolarized in immature hippocampal CA1 neurons
      (postnatal day 7, P7) compared with the adult neurons (P140), and the apparent
      input resistance in immature neurons was higher than that in adult neurons. In
      immature neurons, the threshold for action potential generation was high, and the
      peak amplitude of the action potential was low in comparison with adult neurons.
      A time-dependent inward rectification, at potentials negative than the resting
      potential, was prominent in neurons of P14 and P21. After P21, the resting
      membrane potential, the apparent input resistance, and the threshold and the peak
      amplitude of the action potential did not significantly change with increasing
      age. In adult neurons, application of ischemia-simulating medium caused
      irreversible changes in membrane potential consisting of an initial
      hyperpolarization followed by a slow depolarization and a rapid depolarization.
      Once the rapid depolarization occurred, reintroduction of oxygen and glucose
      failed to restore the membrane potential, a state referred to as irreversible
      membrane dysfunction. In neurons of ages P7 or P14, the initial hyperpolarization
      was not apparent, whereas a slow depolarization followed by a rapid
      depolarization was observed. With development of the neurons, the latency for
      onset of the rapid depolarization became shorter and its maximal slope increased.
      Moreover, neurons of ages P14 or P21 showed a partial or complete recovery after
      reintroduction of oxygen and glucose, unlike mature neurons. In summary, the
      present study has demonstrated that the initial hyperpolarization and rapid
      depolarization induced by in vitro ischemia is age dependent. The rapid
      depolarization is not readily produced in the neurons in age less than P21 during
      ischemic exposure.

PMID- 10200220
TI  - Role of proprioceptive signals from an insect femur-tibia joint in patterning
      motoneuronal activity of an adjacent leg joint.
AB  - Interjoint reflex function of the insect leg contributes to postural control at
      rest or to movement control during locomotor movements. In the stick insect
      (Carausius morosus), we investigated the role that sensory signals from the
      femoral chordotonal organ (fCO), the transducer of the femur-tibia (FT) joint,
      play in patterning motoneuronal activity in the adjacent coxa-trochanteral (CT)
      joint when the joint control networks are in the movement control mode of the
      active behavioral state. In the active behavioral state, sensory signals from the
      fCO induced transitions of activity between antagonistic motoneuron pools, i.e.,
      the levator trochanteris and the depressor trochanteris motoneurons. As such,
      elongation of the fCO, signaling flexion of the FT joint, terminated depressor
      motoneuron activity and initiated activity in levator motoneurons. Relaxation of
      the fCO, signaling extension of the FT joint, induced the opposite transition by
      initiating depressor motoneuron activity and terminating levator motoneuron
      activity. This interjoint influence of sensory signals from the fCO was
      independent of the generation of the intrajoint reflex reversal in the FT joint,
      i.e., the "active reaction," which is released by elongation signals from the
      fCO. The generation of these transitions in activity of trochanteral motoneurons
      barely depended on position or velocity signals from the fCO. This contrasts with
      the situation in the resting behavioral state when interjoint reflex action
      markedly depends on actual fCO stimulus parameters, i.e., position and velocity
      signals. In the active behavioral state, movement signals from the fCO obviously
      trigger or release centrally generated transitions in motoneuron activity, e.g.,
      by affecting central rhythm generating networks driving trochanteral motoneuron
      pools. This conclusion was tested by stimulating the fCO in "fictive rhythmic"
      preparations, activated by the muscarinic agonist pilocarpine in the otherwise
      isolated and deafferented mesothoracic ganglion. In this situation, sensory
      signals from the fCO did in fact reset and entrain rhythmic activity in
      trochanteral motoneurons. The results indicate for the first time that when the
      stick insect locomotor system is active, sensory signals from the proprioceptor
      of one leg joint, i.e., the fCO, pattern motor activity in an adjacent leg joint,
      i.e., the CT joint, by affecting the central rhythm generating network driving
      the motoneurons of the adjacent joint.

PMID- 10200222
TI  - Membrane dysfunction induced by in vitro ischemia in rat hippocampal CA1
      pyramidal neurons.
AB  - Intracellular and single-electrode voltage-clamp recordings were made to
      investigate the process of membrane dysfunction induced by superfusion with
      oxygen and glucose-deprived (ischemia-simulating) medium in hippocampal CA1
      pyramidal neurons of rat tissue slices. To assess correlation between potential
      change and membrane dysfunction, the recorded neurons were stained
      intracellularly with biocytin. A rapid depolarization was produced approximately
      6 min after starting superfusion with ischemia-simulating medium. When oxygen and
      glucose were reintroduced to the bathing medium immediately after generating the
      rapid depolarization, the membrane did not repolarize but depolarized further,
      the potential reaching 0 mV approximately 5 min after the reintroduction. In
      single-electrode voltage-clamp recording, a corresponding rapid inward current
      was observed when the membrane potential was held at -70 mV. After the
      reintroduction of oxygen and glucose, the current induced by ischemia-simulating
      medium partially returned to preexposure levels. These results suggest that the
      membrane depolarization is involved with the membrane dysfunction. The
      morphological aspects of biocytin-stained neurons during ischemic exposure were
      not significantly different from control neurons before the rapid depolarization.
      On the other hand, small blebs were observed on the surface of the neuron within
      0.5 min of generating the rapid depolarization, and blebs increased in size after
      1 min. After 3 min, neurons became larger and swollen. The long and transverse
      axes and area of the cross-sectional cell body were increased significantly 1 and
      3 min after the rapid depolarization. When Ca2+-free (0 mM) with Co2+ (2.5 mM)
      containing medium including oxygen and glucose was applied within 1 min after the
      rapid depolarization, the membrane potential was restored completely to the
      preexposure level in the majority of neurons. In these neurons, the long axis was
      lengthened without any blebs being apparent on the membrane surface. These
      results suggest that the membrane dysfunction induced by in vitro ischemia may be
      due to a Ca2+-dependent process that commences approximately 1.5 min after and is
      completed 3 min after the onset of the rapid depolarization. Because small blebs
      occurred immediately after the rapid depolarization and large blebs appeared 1.5
      3 min after, it is likely that the transformation from small to large blebs may
      result in the observed irreversible membrane dysfunction.

PMID- 10200223
TI  - Functional expression of exogenous proteins in mammalian sensory hair cells
      infected with adenoviral vectors.
AB  - To understand the function of specific proteins in sensory hair cells, it is
      necessary to add or inactivate those proteins in a system where their
      physiological effects can be studied. Unfortunately, the usefulness of
      heterologous expression systems for the study of many hair cell proteins is
      limited by the inherent difficulty of reconstituting the hair cell's exquisite
      cytoarchitecture. Expression of exogenous proteins within hair cells themselves
      may provide an alternative approach. Because recombinant viruses were efficient
      vectors for gene delivery in other systems, we screened three viral vectors for
      their ability to express exogenous genes in hair cells of organotypic cultures
      from mouse auditory and vestibular organs. We observed no expression of the genes
      for beta-galactosidase or green fluorescent protein (GFP) with either herpes
      simplex virus or adeno-associated virus. On the other hand, we found robust
      expression of GFP in hair cells exposed to a recombinant, replication-deficient
      adenovirus that carried the gene for GFP driven by a cytomegalovirus promoter.
      Titers of 4 x 10(7) pfu/ml were sufficient for expression in 50% of the
      approximately 1,000 hair cells in the utricular epithelium; < 1% of the nonhair
      cells in the epithelium were GFP positive. Expression of GFP was evident as early
      as 12 h postinfection, was maximal at 4 days, and continued for at least 10 days.
      Over the first 36 h there was no evidence of toxicity. We recorded normal voltage
      dependent and transduction currents from infected cells identified by GFP
      fluorescence. At longer times hair bundle integrity was compromised despite a
      cell body that appeared healthy. To assess the ability of adenovirus-mediated
      gene transfer to alter hair cell function we introduced the gene for the ion
      channel Kir2.1. We used an adenovirus vector encoding Kir2.1 fused to GFP under
      the control of an ecdysone promoter. Unlike the diffuse distribution within the
      cell body we observed with GFP, the ion channel-GFP fusion showed a pattern of
      fluorescence that was restricted to the cell membrane and a few extranuclear
      punctate regions. Patch-clamp recordings confirmed the expression of an inward
      rectifier with a conductance of 43 nS, over an order of magnitude larger than the
      endogenous inward rectifier. The zero-current potential in infected cells was
      shifted by -17 mV. These results demonstrate an efficient method for gene
      transfer into both vestibular and auditory hair cells in culture, which can be
      used to study the effects of gene products on hair cell function.

PMID- 10200224
TI  - Optical mapping of neural network activity in chick spinal cord at an
      intermediate stage of embryonic development.
AB  - We have applied multiple-site optical recording of transmembrane potential
      changes to recording of neuronal pathway/network activity from embryonic chick
      spinal cord slice preparations. Spinal cord preparations were dissected from 8
      day-old chick embryos at Hamburger-Hamilton stage 33, and transverse slice
      preparations were prepared with the 13th cervical spinal nerve or with the 2nd or
      5th lumbosacral spinal nerve intact. The slice preparations were stained with a
      voltage-sensitive merocyanine-rhodanine dye (NK2761). Transmembrane voltage
      related optical (dye-absorbance) changes evoked by spinal nerve stimulation with
      positive square-current pulses using a suction electrode were recorded
      simultaneously from many loci in the preparation, using a 128- or 1,020-element
      photodiode array. Optical responses were detected from dorsal and ventral regions
      corresponding to the posterior (dorsal) and anterior (ventral) gray horns. The
      optical signals were composed of two components, fast spike-like and slow
      signals. In the dorsal region, the fast spike-like signal was identified as the
      presynaptic action potential in the sensory nerve and the slow signal as the
      postsynaptic potential. In the ventral region, the fast spike-like signal
      reflects the antidromic action potential in motoneurons, and the slow signal is
      related to the postsynaptic potential evoked in the motoneuron. In preparations
      in which the ventral root was cut microsurgically, the antidromic action
      potential-related optical signals were eliminated. The areas of the maximal
      amplitude of the evoked signals in the dorsal and ventral regions were located
      near the dorsal root entry zone and the ventral root outlet zone, respectively.
      Quasiconcentric contour-line maps were obtained in the dorsal and ventral
      regions, suggesting the functional arrangement of the dorsal and ventral synaptic
      connections. Synaptic fatigue induced by repetitive stimuli in the ventral
      synapses was more rapid than in the dorsal synapses. The distribution patterns of
      the signals were essentially similar among C13, LS2, and LS5 preparations,
      suggesting that there is no difference in the spatiotemporal pattern of the
      neural responses along the rostrocaudal axis of the spinal cord at this
      developmental stage. In the ventral root-cut preparations, comparing the delay
      times between the ventral slow optical signals, we have been able to demonstrate
      that neural network-related synaptic connections are generated functionally in
      the embryonic spinal cord at Hamburger-Hamilton stage 33.

PMID- 10200225
TI  - Isodirectional tuning of adjacent interneurons and pyramidal cells during working
      memory: evidence for microcolumnar organization in PFC.
AB  - Studies on the cellular mechanisms of working memory demonstrated that neurons in
      dorsolateral prefrontal cortex (dPFC) exhibit directionally tuned activity during
      an oculomotor delayed response. To determine the particular contributions of
      pyramidal cells and interneurons to spatial tuning in dPFC, we examined both
      individually and in pairs the tuning properties of regular-spiking (RS) and fast
      spiking (FS) units that represent putative pyramidal cells and interneurons,
      respectively. Our main finding is that FS units possess spatially tuned sensory,
      motor, and delay activity (i. e., "memory fields") similar to those found in RS
      units. Furthermore, when recorded simultaneously at the same site, the majority
      of neighboring neurons, whether FS or RS, displayed isodirectional tuning, i.e.,
      they shared very similar tuning angles for the sensory and delay phases of the
      task. As the trial entered the response phase of the task, many FS units shifted
      their direction of tuning and became cross-directional to adjacent RS units by
      the end of the trial. These results establish that a large part of inhibition in
      prefrontal cortex is spatially oriented rather than being untuned and simply
      regulating the threshold response of pyramidal cell output. Moreover, the
      isodirectional tuning between adjacent neurons supports a functional
      microcolumnar organization in dPFC for spatial memory fields similar to that
      found in other areas of cortex for sensory receptive fields.

PMID- 10200226
TI  - Identification of the cerebral loci processing human swallowing with H2(15)O PET
      activation.
AB  - Lesional and electrophysiological data implicate a role for the cerebral cortex
      in the initiation and modulation of human swallowing, and yet its functional
      neuroanatomy remains undefined. We therefore conducted a functional study of the
      cerebral loci processing human volitional swallowing with 15O-labeled water
      positron emission tomography (PET) activation imaging. Regional cerebral
      activation was investigated in 8 healthy right handed male volunteers with a
      randomized 12-scan paradigm of rest and water swallows (5 ml/bolus, continuous
      infusion) at increasing frequencies of 0.1, 0.2, and 0.3 Hz, which were visually
      cued and monitored with submental electromyogram (EMG). Group and individual
      linear covariate analyses were performed with SPM96. In five of eight subjects,
      the cortical motor representation of pharynx was subsequently mapped with
      transcranial magnetic stimulation (TMS) in a posthoc manner to substantiate
      findings of hemispheric differences in sensorimotor cortex activation seen with
      PET. During swallowing, group PET analysis identified increased regional cerebral
      blood flow (rCBF) (P < 0.001) within bilateral caudolateral sensorimotor cortex
      [Brodmann's area (BA) 3, 4, and 6], right anterior insula (BA 16), right
      orbitofrontal and temporopolar cortex (BA 11 and 38), left mesial premotor cortex
      (BA 6 and 24), left temporopolar cortex and amygdala (BA 38 and 34), left
      superiomedial cerebellum, and dorsal brain stem. Decreased rCBF (P < 0.001) was
      also observed within bilateral posterior parietal cortex (BA 7), right anterior
      occipital cortex (BA 19), left superior frontal cortex (BA 8), right prefrontal
      cortex (BA 9), and bilateral superiomedial temporal cortex (BA 41 and 42).
      Individual PET analysis revealed asymmetric representation within sensorimotor
      cortex in six of eight subjects, four lateralizing to right hemisphere and two to
      left hemisphere. TMS mapping in the five subjects identified condordant
      interhemisphere asymmetries in the motor representation for pharynx, consistent
      with the PET findings. We conclude that volitional swallowing recruits multiple
      cerebral regions, in particular sensorimotor cortex, insula, temporopolar cortex,
      cerebellum, and brain stem, the sensorimotor cortex displaying strong degrees of
      interhemispheric asymmetry, further substantiated with TMS. Such findings may
      help explain the variable nature of swallowing disorders after stroke and other
      focal lesions to the cerebral cortex.

PMID- 10200227
TI  - Reacquisition deficits in prism adaptation after muscimol microinjection into the
      ventral premotor cortex of monkeys.
AB  - A small amount of muscimol (1 microl; concentration, 5 microg/microl) was
      injected into the ventral and dorsal premotor cortex areas (PMv and PMd,
      respectively) of monkeys, which then were required to perform a visually guided
      reaching task. For the task, the monkeys were required to reach for a target soon
      after it was presented on a screen. While performing the task, the monkeys' eyes
      were covered with left 10 degrees, right 10 degrees, or no wedge prisms, for a
      block of 50-100 trials. Without the prisms, the monkeys reached the targets
      accurately. When the prisms were placed, the monkeys initially misreached the
      targets because the prisms displaced the visual field. Before the muscimol
      injection, the monkeys adapted to the prisms in 10-20 trials, judging from the
      horizontal distance between the target location and the point where the monkey
      touched the screen. After muscimol injection into the PMv, the monkeys lost the
      ability to readapt and touched the screen closer to the location of the targets
      as seen through the prisms. This deficit was observed at selective target
      locations, only when the targets were shifted contralaterally to the injected
      hemisphere. When muscimol was injected into the PMd, no such deficits were
      observed. There were no changes in the reaction and movement times induced by
      muscimol injections in either area. The results suggest that the PMv plays an
      important role in motor learning, specifically in recalibrating visual and motor
      coordinates.

PMID- 10200228
TI  - Na+-K+-2Cl- cotransporter in immature cortical neurons: A role in intracellular
      Cl- regulation.
AB  - Na+-K+-2Cl- cotransporter has been suggested to contribute to active
      intracellular Cl- accumulation in neurons at both early developmental and adult
      stages. In this report, we extensively characterized the Na+-K+-2Cl-
      cotransporter in primary culture of cortical neurons that were dissected from
      cerebral cortex of rat fetus at embryonic day 17. The Na+-K+-2Cl- cotransporter
      was expressed abundantly in soma and dendritic processes of cortical neurons
      evaluated by immunocytochemical staining. Western blot analysis revealed that an
      approximately 145-kDa cotransporter protein was present in cerebral cortex at the
      early postnatal (P0-P9) and adult stages. There was a time-dependent upregulation
      of the cotransporter activity in cortical neurons during the early postnatal
      development. A substantial level of bumetanide-sensitive K+ influx was detected
      in neurons cultured for 4-8 days in vitro (DIV 4-8). The cotransporter activity
      was increased significantly at DIV 12 and maintained at a steady level throughout
      DIV 12-14. Bumetanide-sensitive K+ influx was abolished completely in the absence
      of either extracellular Na+ or Cl-. Opening of gamma-aminobutyric acid (GABA)
      activated Cl- channel or depletion of intracellular Cl- significantly stimulated
      the cotransporter activity. Moreover, the cotransporter activity was elevated
      significantly by activation of N-methyl-D-aspartate ionotropic glutamate receptor
      via a Ca2+-dependent mechanism. These results imply that the inwardly directed
      Na+-K+-2Cl- cotransporter is important in active accumulation of intracellular Cl
      and may be responsible for GABA-mediated excitatory effect in immature cortical
      neurons.

PMID- 10200229
TI  - Developmental aspects and mechanisms of rat caudal hypothalamic neuronal
      responses to hypoxia.
AB  - Previous reports from this laboratory have shown that a high percentage of
      neurons in the caudal hypothalamus are stimulated by hypoxia both in vivo and in
      vitro. This stimulation is in the form of an increase in firing frequency and
      significant membrane depolarization. The goal of the present study was to
      determine if this hypoxia-induced excitation is influenced by development. In
      addition, we sought to determine the mechanism by which hypoxia stimulates caudal
      hypothalamic neurons. Caudal hypothalamic neurons from neonatal (4-16 days) or
      juvenile (20-40 days) rats were patch-clamped, and the whole cell voltage and
      current responses to moderate (10% O2) or severe (0% O2) hypoxia were recorded in
      the brain slice preparation. Analysis of tissue oxygen levels demonstrated no
      significant difference in the levels of tissue oxygen in brain slices between the
      different age groups. A significantly larger input resistance, time constant and
      half-time to spike height was observed for neonatal neurons compared with
      juvenile neurons. Both moderate and severe hypoxia elicited a net inward current
      in a significantly larger percentage of caudal hypothalamic neurons from rats
      aged 20-40 days (juvenile) as compared with rats aged 4-16 days (neonatal). In
      contrast, there was no difference in the magnitude of the inward current response
      to moderate or severe hypoxia between the two age groups. Those cells that were
      stimulated by hypoxia demonstrated a significant decrease in input resistance
      during hypoxic stimulation that was not observed in those cells unaffected by
      hypoxia. A subset of neurons were tested independent of age for the ability to
      maintain the inward current response to hypoxia during synaptic blockade (11.4 mM
      Mg2+/0. 2 mM Ca2+). Most of the neurons tested (88.9%) maintained a hypoxic
      excitation during synaptic blockade, and this inward current response was
      unaffected by addition of 2 mM cobalt chloride to the bathing medium. In
      contrast, perfusion with the Na+ channel blocker, tetrodotoxin (1-2 microM) or
      Na+ replacement with N-methyl-D-glucamine (NMDG) significantly reduced the inward
      current response to hypoxia. Furthermore, the input resistance decrease observed
      during hypoxia was attenuated significantly during perfusion with NMDG. These
      results indicate the excitation elicited by hypoxia in hypothalamic neurons is
      age dependent. In addition, the inward current response of caudal hypothalamic
      neurons is not dependent on synaptic input but results from a sodium-dependent
      conductance.

PMID- 10200230
TI  - Cerebellar lesions and prism adaptation in macaque monkeys.
AB  - If a laterally displacing prism is placed in front of one eye of a person or
      monkey with the other eye occluded, they initially will point to one side of a
      target that is located directly in front of them. Normally, people and monkeys
      adapt easily to the displaced vision and correct their aim after a few trials. If
      the prism then is removed, there is a postadaptation shift in which the subject
      misses the target and points in the opposite direction for a few trials. We
      tested five Macaque monkeys for their ability to adapt to a laterally displacing
      prism and to show the expected postadaptation shift. When tested as normals, all
      five animals showed the typical pattern of adaptation and postadaptation shift.
      Like human subjects, the monkeys also showed complete interocular transfer of the
      adaptation but no transfer of the adaptation between the two arms. When
      preoperative training and testing was complete, we made lesions of various target
      areas on the cerebellar cortex. A cerebellar lesion that included the dorsal
      paraflocculus and uvula abolished completely the normal prism adaptation for the
      arm ipsilateral to the lesion in one of the five monkeys. The other four animals
      retained the ability to prism-adapt normally and showed the expected
      postadaptation shift. In the one case in which the lesion abolished prism
      adaptation, the damage included Crus I and II, paramedian lobule and the dorsal
      paraflocculus of the cerebellar hemispheres as well as lobule IX, of the vermis.
      Thus in this case, the lesion included virtually all the cerebellar cortex that
      receives mossy-fiber visual information relayed via the pontine nuclei from the
      cerebral cortex. The other four animals had damage to lobule V, the classical
      anterior lobe arm area and/or vermian lobules VI/VII, the oculomotor region. When
      tested postoperatively, some of these animals showed a degree of ataxia
      equivalent to that of the case in which prism adaptation was affected, but prism
      adaptation and the postadaptation shift remained normal. We conclude that in
      addition to its role in long-term motor learning and reflex adaptation, the
      region of the cerebellum that was ablated also may be a critical site for a short
      term motor memory. Prism adaptation seems to involve a region of the cerebellum
      that receives a mossy-fiber visual error signal and probably a corollary
      discharge of the movement.

PMID- 10200231
TI  - Activation of peripheral GABAA receptors inhibits temporomandibular joint-evoked
      jaw muscle activity.
AB  - We have previously shown that injection of mustard oil or glutamate into rat
      temporomandibular joint (TMJ) tissues, an experimental model of acute TMJ injury,
      can reflexly induce a prolonged increase in the activity of both digastric (jaw
      opener) and masseter (jaw-closer) muscles. In this study, GABA was applied to the
      TMJ region by itself or in combination with glutamate, and the magnitude of
      evoked jaw muscle electromyographic (EMG) activity was measured. Application of
      GABA alone to the TMJ region did not evoke significant jaw muscle EMG activity
      when compared with normal saline controls. In contrast, co-application of GABA
      and glutamate into the TMJ region decreased the magnitude of glutamate-evoked EMG
      activity. This GABA-mediated inhibition of glutamate-evoked EMG activity followed
      an inverse dose-response relationship with an estimated median inhibitory dose
      (ID50) of 0.17 +/- 0.05 (SE) micromol and 0.031 +/- 0.006 micromol for the
      digastric and masseter muscles, respectively. Co-administration of the GABAA
      receptor antagonist bicuculline (0.05 micromol) but not the GABAB receptor
      antagonist phaclofen (0.05 or 0. 15 micromol) reversed the suppressive actions of
      GABA, indicating that this action of GABA may be mediated by peripheral GABAA
      receptors located within the TMJ region. Our results suggest that activation of
      peripheral GABAA receptors located within the TMJ region could act to decrease
      the transmission of nociceptive information.

PMID- 10200232
TI  - Thalamic relay site for cold perception in humans.
AB  - The neural pathways subserving the sensation of temperature are virtually
      unknown. However, recent findings in the monkey suggest that the sensation of
      cold may be mediated by an ascending pathway relaying in the posterior part of
      the thalamic ventromedial nucleus (VMpo). To test this hypothesis we examined the
      responses of neurons to thermal stimulation of the skin and determined the
      perceptual effects of microstimulation in the VMpo region in awake patients
      undergoing functional stereotactic surgery. In 16 patients, microstimulation in
      the VMpo region evoked cold sensations in a circumscribed body part. Furthermore,
      at some of these sites thalamic neurons were found that responded to innocuous
      cooling of the skin area corresponding to the stimulation-evoked cold sensations.
      These data provide the first direct demonstration of a pathway mediating cold
      sensation and its location in the human thalamus.

PMID- 10200233
TI  - Cloning and expression of the human kv4.3 potassium channel.
AB  - We report on the cloning and expression of hKv4.3, a fast inactivating,
      transient, A-type potassium channel found in both heart and brain that is 91%
      homologous to the rat Kv4.3 channel. Two isoforms of hKv4.3 were cloned. One is
      full length (hKv4.3 long), and the other has a 19 amino acid deletion (hKv4.3
      short). RT-PCR shows that the brain contains both forms of the channel RNA,
      whereas the heart predominantly has the longer version. Both versions of the
      channel were expressed in Xenopus oocytes, and both contain a significant window
      or noninactivating current seen near potentials of -30 to -40 mV. The
      inactivation curve for hKv4.3 short is shifted 10 mV positive relative to hKv4.3
      long. This causes the peak window current for the short version to occur near -30
      mV and the peak for the longer version to be at -40 mV. There was little
      difference in the recovery from inactivation or in the kinetics of inactivation
      between the two isoforms of the channel.

PMID- 10200234
TI  - Correlation of primate superior colliculus and reticular formation discharge with
      proximal limb muscle activity.
AB  - We studied the discharge of neurons from both the superior colliculus (SC) and
      the underlying mesencephalic reticular formation (MRF) and its relation to the
      simultaneously recorded activity of 11 arm muscles. The 242 neurons tested with a
      center-out reach task yielded 2,586 pairs of neuron/muscle cross-correlations
      (normalized, such that perfect correlations are +/-1.0). Of these, 43% had peaks
      with magnitude as large as 0.15, a value that corresponds to the 5% level of
      significance, and 16% were as large as 0.25. The great majority of peaks in this
      latter group was positive. The median lag time within this group was 52 ms,
      indicating that the neuronal discharge tended to precede the correlated muscle
      activity. We found a small but significantly higher proportion of cells with
      these relatively strong correlations in the MRF than in the SC. For both areas,
      these occurred most frequently with muscles of the shoulder girdle and became
      less frequent for axial as well as for increasingly distal arm musculature. The
      results support a role for the SC and MRF in guiding the arm during reach
      movements via the control of proximal limb musculature.

PMID- 10200235
TI  - Dopaminergic synapses mediate neuronal changes in an analogue of operant
      conditioning.
AB  - Feeding behavior in Aplysia can be modified by operant conditioning in which
      contingent reinforcement is conveyed by the esophageal nerve (E n.). A neuronal
      analogue of this conditioning in the isolated buccal ganglia was developed by
      using stimulation of E n. as an analogue of contingent reinforcement. Previous
      studies indicated that E n. may release dopamine. We used a dopamine antagonist
      (methylergonovine) to investigate whether dopamine mediated the enhancement of
      motor patterns in the analogue of operant conditioning. Methylergonovine blocked
      synaptic connections from the reinforcement pathway and the contingent-dependent
      enhancement of the reinforced pattern. These results suggest that dopamine
      mediates at least part of the neuronal modifications induced by contingent
      reinforcement.

PMID- 10200236
TI  - Endogenous pH shifts facilitate spreading depression by effect on NMDA receptors.
AB  - Rapid extracellular alkalinizations accompany normal neuronal activity and have
      been implicated in the modulation of N-methyl-D-aspartate (NMDA) receptors.
      Particularly large alkaline transients also occur at the onset of spreading
      depression (SD). To test whether these endogenous pH shifts can modulate SD, the
      alkaline shift was amplified using benzolamide, a poorly permeant inhibitor of
      interstitial carbonic anhydrase. SD was evoked by microinjection of 1.2 M KCl
      into the CA1 stratum radiatum of rat hippocampal slices and recorded by a
      proximal double-barreled pH microelectrode and a distal potential electrode. In
      Ringer solution of pH 7.1 containing picrotoxin (but not at a bath pH of 7.4),
      addition of 10 microM benzolamide increased the SD alkaline shift from 0.20 +/-
      0.07 to 0.38 +/- 0.17 unit pH (means +/- SE). This was correlated with a
      significant shortening of the latency and an increase in the conduction velocity
      by 26 +/- 16%. In the presence of the NMDA receptor antagonist DL-2-amino-5
      phosphonovaleric acid (APV), benzolamide still amplified the alkaline transient,
      however, its effect on the SD latency and propagation velocity was abolished. The
      intrinsic modulation of SD by its alkaline transient may play an important role
      under focal ischemic conditions by removing the proton block of NMDA receptors
      where interstitial acidosis would otherwise limit NMDA receptor activity.

PMID- 10200237
TI  - Novel form of spreading acidification and depression in the cerebellar cortex
      demonstrated by neutral red optical imaging.
AB  - A novel form of spreading acidification and depression in the rat cerebellar
      cortex was imaged in vivo using the pH-sensitive dye, Neutral red. Surface
      stimulation evoked an initial beam of increased fluorescence (i.e., decreased pH)
      that spread rostrally and caudally across the folium and into neighboring folia.
      A transient but marked suppression in the excitability of the parallel fiber
      Purkinje cell circuitry accompanied the spread. Characteristics differentiating
      this phenomenon from the spreading depression of Leao include: high speed of
      propagation on the surface (average of 450 microm/s), stable extracellular DC
      potential, no change in blood vessel diameter, and repeatability at short
      intervals. This propagating acidification constitutes a previously unknown class
      of neuronal processing in the cerebellar cortex.

PMID- 10200238
TI  - PNAS policy on prior publication.

PMID- 10200239
TI  - How plants learn.

PMID- 10200240
TI  - Femtochemistry uncovers the nature of electron transfer reactions.

PMID- 10200242
TI  - Supernovae, an accelerating universe and the cosmological constant.
AB  - Observations of supernova explosions halfway back to the Big Bang give plausible
      evidence that the expansion of the universe has been accelerating since that
      epoch, approximately 8 billion years ago and suggest that energy associated with
      the vacuum itself may be responsible for the acceleration.

PMID- 10200243
TI  - Real or virtual large-scale structure?
AB  - Modeling the development of structure in the universe on galactic and larger
      scales is the challenge that drives the field of computational cosmology. Here,
      photorealism is used as a simple, yet expert, means of assessing the degree to
      which virtual worlds succeed in replicating our own.

PMID- 10200244
TI  - Observing the epoch of galaxy formation.
AB  - Significant observational progress in addressing the question of the origin and
      early evolution of galaxies has been made in the past few years, allowing for
      direct comparison of the epoch when most of the stars in the universe were
      forming to prevailing theoretical models. There is currently broad consistency
      between theoretical expectations and the observations, but rapid improvement in
      the data will provide much more critical tests of theory in the coming years.

PMID- 10200241
TI  - Tossing monkey wrenches into the clock: new ways of treating cancer.

PMID- 10200245
TI  - Scaling the universe: gravitational lenses and the Hubble constant.
AB  - Gravitational lenses, besides being interesting in their own right, have been
      demonstrated to be suitable as "gravitational standard rulers" for the
      measurement of the rate of expansion of the Universe (Ho), as well as to
      constrain the values of the cosmological parameters such as Omegao and Lambdao
      that control the evolution of the volume of the Universe with cosmic time.

PMID- 10200247
TI  - V-Amylose at atomic resolution: X-ray structure of a cycloamylose with 26 glucose
      residues (cyclomaltohexaicosaose).
AB  - The amylose fraction of starch occurs in double-helical A- and B-amyloses and the
      single-helical V-amylose. The latter contains a channel-like central cavity that
      is able to include molecules, "iodine's blue" being the best-known
      representative. Molecular models of these amylose forms have been deduced by
      solid state 13C cross-polarization/magic angle spinning NMR and by x-ray fiber
      and electron diffraction combined with computer-aided modeling. They remain
      uncertain, however, as no structure at atomic resolution is available. We report
      here the crystal structure of a hydrated cycloamylose containing 26 glucose
      residues (cyclomaltohexaicosaose, CA26), which has been determined by
      real/reciprocal space recycling starting from randomly positioned atoms or from
      an oriented diglucose fragment. This structure provides conclusive evidence for
      the structure of V-amylose, as the macrocycle of CA26 is folded into two short
      left-handed V-amylose helices in antiparallel arrangement and related by twofold
      rotational pseudosymmetry. In the V-helices, all glucose residues are in syn
      orientation, forming systematic interglucose O(3)n...O(2)(n+l) and
      O(6)n...O(2)(n+6)/O(3)(n+6) hydrogen bonds; the central cavities of the V-helices
      are filled by disordered water molecules. The folding of the CA26 macrocycle is
      characterized by typical "band-flips" in which diametrically opposed glucose
      residues are in anti rather than in the common syn orientation, this conformation
      being stabilized by interglucose three-center hydrogen bonds with O(3)n as donor
      and O(5)(n+l), O(6)(n+l) as acceptors. The structure of CA26 permitted
      construction of an idealized V-amylose helix, and the band-flip motif explains
      why V-amylose crystallizes readily and may be packed tightly in seeds.

PMID- 10200246
TI  - New insights into tumor suppression: PTEN suppresses tumor formation by
      restraining the phosphoinositide 3-kinase/AKT pathway.
AB  - The most recently discovered PTEN tumor suppressor gene has been found to be
      defective in a large number of human cancers. In addition, germ-line mutations in
      PTEN result in the dominantly inherited disease Cowden syndrome, which is
      characterized by multiple hamartomas and a high proclivity for developing cancer.
      A series of publications over the past year now suggest a mechanism by which PTEN
      loss of function results in tumors. PTEN appears to negatively control the
      phosphoinositide 3-kinase signaling pathway for regulation of cell growth and
      survival by dephosphorylating the 3 position of phosphoinositides.

PMID- 10200248
TI  - Demonstration of the parity-violating energy difference between enantiomers.
AB  - Racemic mixtures of (+) and (-) sodium potassium tartrate, tris(1, 2
      ethanediamine)cobalt(III), and tris(1,2-ethanediamine)iridium(III) molecules were
      crystallized, and the optical activities of the resulting crystalline materials,
      dissolved in water, were carefully measured to study the influence of the parity
      violating energy difference in the crystallization process. Although no effect
      was found in the case of tartrate, enantiomeric excess appeared in the
      crystallization of the cobalt and iridium complexes. These investigations,
      performed in our laboratory, demonstrated the contribution of the parity
      violating neutral weak current to the forces acting in molecules.

PMID- 10200249
TI  - A common pharmacophore for cytotoxic natural products that stabilize
      microtubules.
AB  - Taxol (paclitaxel), a complex diterpene obtained from the Pacific yew, Taxus
      brevifolia, is arguably the most important new drug in cancer chemotherapy. The
      mechanism of cytotoxic action for paclitaxel-i.e., the stabilization of
      microtubules leading to mitotic arrest-is now shared by four recently identified
      natural products, eleutherobin, epothilones A and B, and discodermolide. Their
      ability to competitively inhibit [3H]paclitaxel binding to microtubules strongly
      suggests the existence of a common binding site. Recently, we have developed
      nonaromatic analogues of paclitaxel that maintain high cytotoxicity and tubulin
      binding (e.g., nonataxel). We now propose a common pharmacophore that unites
      paclitaxel, nonataxel, the epothilones, eleutherobin, and discodermolide, and
      rationalizes the extensive structure-activity relationship data pertinent to
      these compounds. Insights from the common pharmacophore have enabled the
      development of a hybrid construct with demonstrated cytotoxic and tubulin-binding
      activity.

PMID- 10200250
TI  - High-efficiency gene transfer into skeletal muscle mediated by electric pulses.
AB  - Gene delivery to skeletal muscle is a promising strategy for the treatment of
      muscle disorders and for the systemic secretion of therapeutic proteins. However,
      present DNA delivery technologies have to be improved with regard to both the
      level of expression and interindividual variability. We report very efficient
      plasmid DNA transfer in muscle fibers by using square-wave electric pulses of low
      field strength (less than 300 V/cm) and of long duration (more than 1 ms).
      Contrary to the electropermeabilization-induced uptake of small molecules into
      muscle fibers, plasmid DNA has to be present in the tissue during the electric
      pulses, suggesting a direct effect of the electric field on DNA during
      electrotransfer. This i.m. electrotransfer method increases reporter and
      therapeutic gene expression by several orders of magnitude in various muscles in
      mouse, rat, rabbit, and monkey. Moreover, i.m. electrotransfer strongly decreases
      variability. Stability of expression was observed for at least 9 months. With a
      pCMV-FGF1 plasmid coding for fibroblast growth factor 1, this protein was
      immunodetected in the majority of muscle fibers subjected to the electric pulses.
      DNA electrotransfer in muscle may have broad applications in gene therapy and in
      physiological, pharmacological, and developmental studies.

PMID- 10200251
TI  - A mutation in the heterotrimeric stimulatory guanine nucleotide binding protein
      alpha-subunit with impaired receptor-mediated activation because of elevated
      GTPase activity.
AB  - It has been reported that substitution of Arg258, a residue within the GTPase
      domain of the heterotrimeric guanine nucleotide binding protein (G protein) alpha
      subunit (alphas), to alanine (alphas-R258A) results in decreased activation by
      receptor or aluminum fluoride (AlF4-) and increased basal GDP release. Arg258
      interacts with Gln170 in the helical domain, and, presumably, loss of this
      interaction between the GTPase and helical domain leads to more rapid GDP
      release, resulting in decreased activation by AlF4- and increased thermolability.
      In this study, we mutate Gln170 to alanine (alphas-Q170A) and demonstrate that
      this mutant, like alphas-R258A, has decreased activation by AlF4-, increased
      thermolability (both reversed in the presence of excess guanine nucleotide), and
      an increased rate of GDP release. However, unlike alphas-R258A, alphas-Q170A does
      not have impaired receptor-mediated activation. Therefore, this interdomain
      interaction is critical to maintain normal guanine nucleotide binding (and hence
      normal activation by AlF4-) but is not important for receptor-mediated
      activation. In single turnover GTPase assays, the catalytic rate for GTP
      hydrolysis of alphas-R258A was 14-fold higher than normal whereas that of alphas
      Q170A was unaffected. Examination of the alphas crystal structure suggests that
      Arg258, through interactions with Glu50, might constrain the position of Arg201,
      a residue critical for catalyzing the GTPase reaction. This is an example of a
      mutation in a heterotrimeric G protein that results in an increased intrinsic
      GTPase activity and provides another mechanism by which G protein mutations can
      impair signal transduction.

PMID- 10200252
TI  - Structure-based design of submicromolar, biologically active inhibitors of
      trypanosomatid glyceraldehyde-3-phosphate dehydrogenase.
AB  - The bloodstream stage of Trypanosoma brucei and probably the intracellular
      (amastigote) stage of Trypanosoma cruzi derive all of their energy from
      glycolysis. Inhibiting glycolytic enzymes may be a novel approach for the
      development of antitrypanosomatid drugs provided that sufficient parasite versus
      host selectivity can be obtained. Guided by the crystal structures of human, T.
      brucei, and Leishmania mexicana glyceraldehyde-3-phosphate dehydrogenase, we
      designed adenosine analogs as tight binding inhibitors that occupy the pocket on
      the enzyme that accommodates the adenosyl moiety of the NAD+ cosubstrate.
      Although adenosine is a very poor inhibitor, IC50 approximately 50 mM, addition
      of substituents to the 2' position of ribose and the N6-position of adenosine led
      to disubstituted nucleosides with micromolar to submicromolar potency in
      glyceraldehyde-3-phosphate dehydrogenase assays, an improvement of 5 orders of
      magnitude over the lead. The designed compounds do not inhibit the human
      glycolytic enzyme when tested up to their solubility limit (approximately 40
      microM). When tested against cultured bloodstream T. brucei and intracellular T.
      cruzi, N6-(1-naphthalenemethyl)-2'-(3-chlorobenzamido)adenosine inhibited growth
      in the low micromolar range. Within minutes after adding this compound to
      bloodstream T. brucei, production of glucose-derived pyruvate ceased, parasite
      motility was lost, and a mixture of grossly deformed and lysed parasites was
      observed. These studies underscore the feasibility of using structure-based drug
      design to transform a mediocre lead compound into a potent enzyme inhibitor. They
      also suggest that energy production can be blocked in trypanosomatids with a
      tight binding competitive inhibitor of an enzyme in the glycolytic pathway.

PMID- 10200253
TI  - Rings and filaments of beta protein from bacteriophage lambda suggest a
      superfamily of recombination proteins.
AB  - The beta protein of bacteriophage lambda acts in homologous genetic recombination
      by catalyzing the annealing of complementary single-stranded DNA produced by the
      lambda exonuclease. It has been shown that the beta protein binds to the products
      of the annealing reaction more tightly than to the initial substrates. We find
      that beta protein exists in three structural states. In the absence of DNA, beta
      protein forms inactive rings with approximately 12 subunits. The active form of
      the beta protein in the presence of oligonucleotides or single-stranded DNA is a
      ring, composed of approximately 15-18 subunits. The double-stranded products of
      the annealing reaction catalyzed by the rings are bound by beta protein in a left
      handed helical structure, which protects the products from nucleolytic
      degradation. These observations suggest structural homology for a family of
      proteins, including the phage P22 erf, the bacterial RecT, and the eukaryotic
      Rad52 proteins, all of which are involved in homologous recombination.

PMID- 10200254
TI  - Assigning protein functions by comparative genome analysis: protein phylogenetic
      profiles.
AB  - Determining protein functions from genomic sequences is a central goal of
      bioinformatics. We present a method based on the assumption that proteins that
      function together in a pathway or structural complex are likely to evolve in a
      correlated fashion. During evolution, all such functionally linked proteins tend
      to be either preserved or eliminated in a new species. We describe this property
      of correlated evolution by characterizing each protein by its phylogenetic
      profile, a string that encodes the presence or absence of a protein in every
      known genome. We show that proteins having matching or similar profiles strongly
      tend to be functionally linked. This method of phylogenetic profiling allows us
      to predict the function of uncharacterized proteins.

PMID- 10200255
TI  - Crystal structure of the CD2-binding domain of CD58 (lymphocyte function
      associated antigen 3) at 1.8-A resolution.
AB  - The binding of the cell surface molecule CD58 (formerly lymphocyte function
      associated antigen 3) to its ligand, CD2, significantly increases the sensitivity
      of antigen recognition by T cells. This was the first heterophilic cell adhesion
      interaction to be discovered and is now an important paradigm for analyzing the
      structural basis of cell-cell recognition. The crystal structure of a CD2-binding
      chimeric form of CD58, solved to 1.8-A resolution, reveals that the ligand
      binding domain of CD58 has the expected Ig superfamily V-set topology and shares
      several of the hitherto unique structural features of CD2, consistent with
      previous speculation that the genes encoding these molecules arose via
      duplication of a common precursor. Nevertheless, evidence for considerable
      divergence of CD2 and CD58 is also implicit in the structures. Mutations that
      disrupt CD2 binding map to the highly acidic surface of the AGFCC'C" beta-sheet
      of CD58, which, unexpectedly, lacks marked shape complementarity to the
      equivalent, rather more basic CD58-binding face of human CD2. The specificity of
      the very weak interactions of proteins mediating cell-cell recognition may often
      derive largely from electrostatic complementarity, with shape matching at the
      protein-protein interface being less exact than for interactions that combine
      specificity with high affinity, such as those involving antibodies.

PMID- 10200256
TI  - The Cys4 zinc finger of bacteriophage T7 primase in sequence-specific single
      stranded DNA recognition.
AB  - Bacteriophage T7 DNA primase recognizes 5'-GTC-3' in single-stranded DNA. The
      primase contains a single Cys4 zinc-binding motif that is essential for
      recognition. Biochemical and mutagenic analyses suggest that the Cys4 motif
      contacts cytosine of 5'-GTC-3' and may also contribute to thymine recognition.
      Residues His33 and Asp31 are critical for these interactions. Biochemical
      analysis also reveals that T7 primase selectively binds CTP in the absence of
      DNA. We propose that bound CTP selects the remaining base G, of 5'-GTC-3', by
      base pairing. Our deduced mechanism for recognition of ssDNA by Cys4 motifs bears
      little resemblance to the recognition of trinucleotides of double-stranded DNA by
      Cys2His2 zinc fingers.

PMID- 10200257
TI  - Location of translational initiation factor IF3 on the small ribosomal subunit.
AB  - The location of translational initiation factor IF3 bound to the 30S subunit of
      the Thermus thermophilus ribosome has been determined by cryoelectron microscopy.
      Both the 30S.IF3 complex and control 30S subunit structures were determined to 27
      A resolution. The difference map calculated from the two reconstructions reveals
      three prominent lobes of positive density. The previously solved crystal
      structure of IF3 fits very well into two of these lobes, whereas the third lobe
      probably arises from conformational changes induced in the 30S subunit as a
      result of IF3 binding. Our placement of IF3 on the 30S subunit allows an
      understanding in structural terms of the biochemical functions of this initiation
      factor, namely its ability to dissociate 70S ribosomes into 30S and 50S subunits
      and the preferential selection of initiator tRNA by IF3 during initiation.

PMID- 10200258
TI  - DRONC, an ecdysone-inducible Drosophila caspase.
AB  - Caspases play an essential role in the execution of programmed cell death in
      metazoans. Although 14 caspases are known in mammals, only a few have been
      described in other organisms. Here we describe the identification and
      characterization of a Drosophila caspase, DRONC, that contains an amino terminal
      caspase recruitment domain. Ectopic expression of DRONC in cultured cells
      resulted in apoptosis, which was inhibited by the caspase inhibitors p35 and
      MIHA. DRONC exhibited a substrate specificity similar to mammalian caspase-2.
      DRONC is ubiquitously expressed in Drosophila embryos during early stages of
      development. In late third instar larvae, dronc mRNA is dramatically up-regulated
      in salivary glands and midgut before histolysis of these tissues. Exposure of
      salivary glands and midgut isolated from second instar larvae to ecdysone
      resulted in a massive increase in dronc mRNA levels. These results suggest that
      DRONC is an effector of steroid-mediated apoptosis during insect metamorphosis.

PMID- 10200259
TI  - A MHC-encoded ubiquitin-like protein (FAT10) binds noncovalently to the spindle
      assembly checkpoint protein MAD2.
AB  - Recently a number of nonclass I genes were discovered in the human MHC class I
      region. One of these, FAT10, encodes a protein consisting of two domains with
      homology to ubiquitin. FAT10 mRNA is expressed constitutively in some
      lymphoblastoid lines and dendritic cells and in certain other cells after gamma
      interferon induction. FAT10 protein expression is controlled at several levels
      including transcription, translation, and protein stability. Yeast two-hybrid
      screening of a human lymphocyte library and immunoprecipitation studies revealed
      that FAT10 noncovalently associated with MAD2, a protein implicated in a cell
      cycle checkpoint for spindle assembly during anaphase. Thus, FAT10 may modulate
      cell growth during B cell or dendritic cell development and activation.

PMID- 10200260
TI  - Crystal structure of human T cell leukemia virus type 1 gp21 ectodomain
      crystallized as a maltose-binding protein chimera reveals structural evolution of
      retroviral transmembrane proteins.
AB  - Retroviral entry into cells depends on envelope glycoproteins, whereby receptor
      binding to the surface-exposed subunit triggers membrane fusion by the
      transmembrane protein (TM) subunit. We determined the crystal structure at 2.5-A
      resolution of the ectodomain of gp21, the TM from human T cell leukemia virus
      type 1. The gp21 fragment was crystallized as a maltose-binding protein chimera,
      and the maltose-binding protein domain was used to solve the initial phases by
      the method of molecular replacement. The structure of gp21 comprises an N
      terminal trimeric coiled coil, an adjacent disulfide-bonded loop that stabilizes
      a chain reversal, and a C-terminal sequence structurally distinct from HIV type
      1/simian immunodeficiency virus gp41 that packs against the coil in an extended
      antiparallel fashion. Comparison of the gp21 structure with the structures of
      other retroviral TMs contrasts the conserved nature of the coiled coil-forming
      region and adjacent disulfide-bonded loop with the variable nature of the C
      terminal ectodomain segment. The structure points to these features having
      evolved to enable the dual roles of retroviral TMs: conserved fusion function and
      an ability to anchor diverse surface-exposed subunit structures to the virion
      envelope and infected cell surface. The structure of gp21 implies that the N
      terminal fusion peptide is in close proximity to the C-terminal transmembrane
      domain and likely represents a postfusion conformation.

PMID- 10200261
TI  - Selective killing of transformed cells by cyclin/cyclin-dependent kinase 2
      antagonists.
AB  - Recent studies identified a short peptide motif that serves as a docking site for
      cyclin/cyclin-dependent kinase (cdk) 2 complexes. Peptides containing this motif
      block the phosphorylation of substrates by cyclin A/cdk2 or cyclin E/cdk2. Here
      we report that cell membrane-permeable forms of such peptides preferentially
      induced transformed cells to undergo apoptosis relative to nontransformed cells.
      Deregulation of E2F family transcription factors is a common event during
      transformation and was sufficient to sensitize cells to the cyclin/cdk2
      inhibitory peptides. These results suggest that deregulation of E2F and
      inhibition of cdk2 are synthetically lethal and provide a rationale for the
      development of cdk2 antagonists as antineoplastic agents.

PMID- 10200262
TI  - RXP 407, a phosphinic peptide, is a potent inhibitor of angiotensin I converting
      enzyme able to differentiate between its two active sites.
AB  - The human somatic angiotensin converting enzyme (ACE) contains two homologous
      domains, each bearing a zinc-dependent active site. All of the synthetic
      inhibitors of this enzyme used in clinical applications interact with these two
      active sites to a similar extent. Recently, several lines of evidence have
      suggested that the N-terminal active site of ACE might be involved in specific
      hydrolysis of some important physiological substrates, like Acetyl-Seryl-Aspartyl
      Lysyl-Proline, a negative regulator of hematopoietic stem cell differentiation
      and proliferation. These findings have stimulated studies aimed at identifying
      new ACE inhibitors able to block only one of the two active sites of this enzyme.
      By screening phosphinic peptide libraries, we discovered a phosphinic peptide Ac
      Asp-(L)Phepsi(PO2-CH2)(L)Ala-Ala-NH2, called RXP 407, which is able to
      differentiate the two ACE active sites, with a dissociation constant three orders
      of magnitude lower for the N-domain of the enzyme. The usefulness of a
      combinatorial chemistry approach to develop new lead structures is underscored by
      the unusual chemical structure of RXP 407, as compared with classical ACE
      inhibitors. As a highly potent and selective inhibitor of the N-terminal active
      site of wild ACE (Ki = 12 nM), RXP 407, which is metabolically stable in vivo,
      may lead to a new generation of ACE inhibitors able to block in vivo only a
      subset of the different functions regulated by ACE.

PMID- 10200263
TI  - BglG, the transcriptional antiterminator of the bgl system, interacts with the
      beta' subunit of the Escherichia coli RNA polymerase.
AB  - The Escherichia coli BglG protein antiterminates transcription at two terminator
      sites within the bgl operon in response to the presence of beta-glucosides in the
      growth medium. BglG was previously shown to be an RNA-binding protein that
      recognizes a specific sequence located just upstream of each of the terminators
      and partially overlapping with them. We show here that BglG also binds to the E.
      coli RNA polymerase, both in vivo and in vitro. By using several techniques, we
      identified the beta' subunit of RNA polymerase as the target for BglG binding.
      The region that contains the binding site for BglG was mapped to the N-terminal
      region of beta'. The beta' subunit, produced in excess, prevented BglG activity
      as a transcriptional antiterminator. Possible roles of the interaction between
      BglG and the polymerase beta' subunit are discussed.

PMID- 10200264
TI  - Universal conservation in translation initiation revealed by human and archaeal
      homologs of bacterial translation initiation factor IF2.
AB  - Binding of initiator methionyl-tRNA to ribosomes is catalyzed in prokaryotes by
      initiation factor (IF) IF2 and in eukaryotes by eIF2. The discovery of both IF2
      and eIF2 homologs in yeast and archaea suggested that these microbes possess an
      evolutionarily intermediate protein synthesis apparatus. We describe the
      identification of a human IF2 homolog, and we demonstrate by using in vivo and in
      vitro assays that human IF2 functions as a translation factor. In addition, we
      show that archaea IF2 can substitute for its yeast homolog both in vivo and in
      vitro. We propose a universally conserved function for IF2 in facilitating the
      proper binding of initiator methionyl-tRNA to the ribosomal P site.

PMID- 10200265
TI  - The membrane-attached electron carrier cytochrome cy from Rhodobacter sphaeroides
      is functional in respiratory but not in photosynthetic electron transfer.
AB  - Rhodobacter species are useful model organisms for studying the structure and
      function of c type cytochromes (Cyt c), which are ubiquitous electron carriers
      with essential functions in cellular energy and signal transduction. Among these
      species, Rhodobacter capsulatus has a periplasmic Cyt c2Rc and a membrane-bound
      bipartite Cyt cyRc. These electron carriers participate in both respiratory and
      photosynthetic electron-transfer chains. On the other hand, until recently,
      Rhodobacter sphaeroides was thought to have only one of these two cytochromes,
      the soluble Cyt c2Rs. Recent work indicated that this species has a gene, cycYRs,
      that is highly homologous to cycYRc, and in the work presented here, functional
      properties of its gene product (Cyt cyRs) are defined. It was found that Cyt cyRs
      is unable to participate in photosynthetic electron transfer, although it is
      active in respiratory electron transfer, unlike its R. capsulatus counterpart,
      Cyt cyRc. Chimeric constructs have shown that the photosynthetic incapability of
      Cyt cyRs is caused, at least in part, by its redox active subdomain, which
      carries the covalently bound heme. It, therefore, seems that this domain
      interacts differently with distinct redox partners, like the photochemical
      reaction center and the Cyt c oxidase, and allows the bacteria to funnel
      electrons efficiently to various destinations under different growth conditions.
      These findings raise an intriguing evolutionary issue in regard to cellular
      apoptosis: why do the mitochondria of higher organisms, unlike their bacterial
      ancestors, use only one soluble electron carrier in their respiratory electron
      transport chains?

PMID- 10200266
TI  - The NDUFA1 gene product (MWFE protein) is essential for activity of complex I in
      mammalian mitochondria.
AB  - The MWFE polypeptide of mammalian complex I (the proton-translocating NADH
      quinone oxidoreductase) is 70 amino acids long, and it is predicted to be a
      membrane protein. The NDUFA1 gene encoding the MWFE polypeptide is located on the
      X chromosome. This polypeptide is 1 of approximately 28 "accessory proteins"
      identified in complex I, which is composed of 42 unlike subunits. It was
      considered accessory, because it is not one of the 14 polypeptides making up the
      core complex I; a homologous set of 14 polypeptides can make a fully functional
      proton-translocating NADH-quinone oxidoreductase in prokaryotes. One MWFE mutant
      has been identified and isolated from a collection of respiration-deficient
      Chinese hamster cell mutants. The CCL16-B2 mutant has suffered a deletion that
      would produce a truncated and abnormal MWFE protein. In these mutant cells,
      complex I activity is reduced severely (<10%). Complementation with hamster
      NDUFA1 cDNA restored the rotenone-sensitive complex I activity of these mutant
      cells to approximately 100% of the parent cell activity. Thus, it is established
      that the MWFE polypeptide is absolutely essential for an active complex I in
      mammals.

PMID- 10200267
TI  - Acyl homoserine-lactone quorum-sensing signal generation.
AB  - Acyl homoserine lactones (acyl-HSLs) are important intercellular signaling
      molecules used by many bacteria to monitor their population density in quorum
      sensing control of gene expression. These signals are synthesized by members of
      the LuxI family of proteins. To understand the mechanism of acyl-HSL synthesis we
      have purified the Pseudomonas aeruginosa RhlI protein and analyzed the kinetics
      of acyl-HSL synthesis by this enzyme. Purified RhlI catalyzes the synthesis of
      acyl-HSLs from acyl-acyl carrier proteins and S-adenosylmethionine. An analysis
      of the patterns of product inhibition indicated that RhlI catalyzes signal
      synthesis by a sequential, ordered reaction mechanism in which S
      adenosylmethionine binds to RhlI as the initial step in the enzymatic mechanism.
      Because pathogenic bacteria such as P. aeruginosa use acyl-HSL signals to
      regulate virulence genes, an understanding of the mechanism of signal synthesis
      and identification of inhibitors of signal synthesis has implications for
      development of quorum sensing-targeted antivirulence molecules.

PMID- 10200268
TI  - A molecular trigger of lipid binding-induced opening of a helix bundle
      exchangeable apolipoprotein.
AB  - Apolipophorin III (apoLp-III) from the sphinx moth, Manduca sexta, is a helix
      bundle protein that interacts reversibly with lipoproteins. Its five elongated
      amphipathic alpha-helices are organized in an antiparallel fashion, with helices
      3 and 4 connected by a short 6-residue (PDVEKE) linker helix, termed helix 3'.
      Upon interaction with lipoproteins, apoLp-III opens to expose a continuous
      hydrophobic interior. It was postulated that helix bundle opening is preceded by
      an initiation step wherein helix 3' serves to recognize available lipoprotein
      surface binding sites. To test this hypothesis, helix 3' was replaced by residues
      that have a propensity to form a type I beta-turn, NPNG. This mutant apoLp-III
      was defective in lipoprotein binding assays. To define a more precise mode of
      interaction, the relevance of the presence of the hydrophobic Val-97 flanked by
      Asp-96 and Glu-98 was investigated by site-directed mutagenesis. V97N and
      D96N/V97N/E98Q apoLp-III were unable to compete with wild-type apoLp-III to
      initiate an interaction with lipoproteins, whereas D96N/E98Q apoLp-III was as
      competent as wild-type apoLp-III. The results suggest that Val-97 is critical,
      whereas Asp-96 and Glu-98 are irrelevant for initiating binding to lipoproteins.
      A model of binding is presented wherein apoLp-III is oriented with the helix 3'
      end of the molecule juxtaposed to the lipoprotein surface. Recognition of
      lipoprotein surface hydrophobic defects by Val-97 triggers opening of the helix
      bundle and facilitates formation of a stable binding interaction.

PMID- 10200269
TI  - Oligoribonuclease is an essential component of the mRNA decay pathway.
AB  - mRNA decay in prokaryotic cells involves the action of both endo- and
      exoribonucleases. In Escherichia coli, degradation of RNA to the mononucleotide
      level was thought to depend on RNase II and polynucleotide phosphorylase. Here,
      we show that the enzyme oligoribonuclease is an essential part of this process as
      well. Thus, inactivation of the orn gene encoding oligoribonuclease leads to a
      cessation of cell growth. Moreover, although pulse-labeled RNA decays normally in
      orn mutant cells under nonpermissive conditions, a large fraction of the
      resulting products is small oligoribonucleotides rather than the mononucleotides
      generated in wild-type cells. The oligoribonucleotides that accumulate are 2-5
      residues in length; longer molecules disappear during the decay process. These
      data indicate that oligoribonuclease is required to complete the degradation of
      mRNA to mononucleotides and that this process is required for cell viability.
      Inasmuch as close homologues of the orn gene are found in a wide range of
      eukaryotes, extending up to humans, these findings raise the possibility that
      oligoribonuclease also participates in mRNA degradation in these organisms.

PMID- 10200271
TI  - Triple-helix formation of DNA oligomers with methylthiourea-linked nucleosides
      (DNmt): a kinetic and thermodynamic analysis.
AB  - Complementary short-strand DNA homooligomers and methylthiourea-linked
      homonucleosides associate and form triplexes in solution. The melting
      temperatures, Tm, the association and dissociation kinetic and thermodynamic
      parameters, and activation energies were determined by UV thermal analysis for
      the triplexes of short-strand DNA homooligomers [d(pA)10-d(pA)23] and poly(dA)
      with the methylthiourea-linked nucleoside [5'-NH3+-d(Tmt)4-T-OH [DNmt5]].
      Circular dichroism studies show evidence of triple-helical association dependent
      on the length of the target homooligomer. The melting and cooling curves exhibit
      hysteresis behavior in the temperature range of 10-95 degrees C at 0.13 deg/min
      thermal rate. From these curves, the rate constants and the energies of
      activation for association (kon, Eon) and dissociation (koff, Eoff) were
      obtained. Tm decreases with the ionic strength and increases with increase in
      length of the monomers. The rate constants kon and koff at a given temperature
      (288 K-310 K) are dependent on the DNA strand length and also decrease and
      increase respectively with the ionic strength. The energies of activation for the
      association and dissociation processes are in the range of -18 to -38 kcal/mol
      and 3 to 18 kcal/mol, respectively. The equilibrium constant for the formation of
      the triplexes [5'-NH3+-d(Tmt)4-T-OH)2.d(pA)x, x = 10-23] is several orders of
      magnitude greater when compared with the triplexes of DNA. The number of base
      triplets in the nucleus of the DNmt2.DNA triple-helix (nucleation-zipping model)
      increases with decreased DNA oligomer length and with increased ionic strength.
      The values of DeltaH degrees calculated from the activation parameters are
      between -30 and -50 kcal/(mol base) and the values of DeltaG degrees are between 
      6 and -11 kcal/(mol base) for short-strand DNA.

PMID- 10200270
TI  - Effects of mutant p53 expression on human 15-lipoxygenase-promoter activity and
      murine 12/15-lipoxygenase gene expression: evidence that 15-lipoxygenase is a
      mutator gene.
AB  - Human 15-lipoxygenase (h15-LO) is present on chromosome 17p13.3 in close
      proximity to the tumor-suppressor gene, p53. 15-LO is implicated in
      antiinflammation, membrane remodeling, and cancer development/metastasis. The
      murine BALB/c embryo fibroblast cell line, (10)1val, expresses p53 in mutant (mt)
      conformation when grown at 39 degrees C and in wild-type conformation when grown
      at 32 degrees C. Transfection of h15-LO promoter constructs (driving luciferase
      reporter) into (10)1val cells and into p53-deficient (10)1 cells resulted in a
      marked increase in h15-LO promoter activity in (10)1val cells at 39 degrees C,
      but not at 32 degrees C, or as compared with (10)1 cells. Transfection of h15-LO
      promoter deletion constructs, however, resulted in total loss of activity in both
      cell types at 32 degrees C and 39 degrees C. Cotransfection of (10)1 cells with
      h15-LO promoter (driving luciferase reporter) along with increasing levels of a
      mt p53 expression vector demonstrated dose-dependent capacity of mt p53 to induce
      15-LO promoter activity. No effect was observed with wild-type p53. In contrast
      to h15-LO promoter activity, (10)1val cells had significantly lower levels of
      endogenous (murine) 12/15-LO (mouse analog of h15-LO) mRNA and protein when grown
      at 39 degrees C compared with cells grown at 32 degrees C. Our data support the
      hypothesis that loss of a tumor-suppressor gene (p53), or "gain-of-function
      activities" resulting from the expression of its mutant forms, regulates 15-LO
      promoter activity in man and in mouse, albeit in directionally opposite manners.
      The studies define a direct link between 15-LO activity and an established tumor
      suppressor gene located in close chromosomal proximity.

PMID- 10200272
TI  - RNA polymerase switch in transcription of yeast rDNA: role of transcription
      factor UAF (upstream activation factor) in silencing rDNA transcription by RNA
      polymerase II.
AB  - Transcription factor UAF (upstream activation factor) is required for a high
      level of transcription, but not for basal transcription, of rDNA by RNA
      polymerase I (Pol I) in the yeast Saccharomyces cerevisiae. RRN9 encodes one of
      the UAF subunits. We have found that rrn9 deletion mutants grow extremely slowly
      but give rise to faster growing variants that can grow without intact Pol I,
      synthesizing rRNA by using RNA polymerase II (Pol II). This change is reversible
      and does not involve a simple mutation. The two alternative states, one suitable
      for rDNA transcription by Pol I and the other favoring rDNA transcription by Pol
      II, are heritable not only in mitosis, but also in meiosis. Thus, S. cerevisiae
      has an inherent ability to transcribe rDNA by Pol II, but this transcription
      activity is silenced in normal cells, and UAF plays a key role in this silencing
      by stabilizing the first state.

PMID- 10200273
TI  - Prebiotic cytosine synthesis: a critical analysis and implications for the origin
      of life.
AB  - A number of theories propose that RNA, or an RNA-like substance, played a role in
      the origin of life. Usually, such hypotheses presume that the Watson-Crick bases
      were readily available on prebiotic Earth, for spontaneous incorporation into a
      replicator. Cytosine, however, has not been reported in analyses of meteorites
      nor is it among the products of electric spark discharge experiments. The
      reported prebiotic syntheses of cytosine involve the reaction of cyanoacetylene
      (or its hydrolysis product, cyanoacetaldehyde), with cyanate, cyanogen, or urea.
      These substances undergo side reactions with common nucleophiles that appear to
      proceed more rapidly than cytosine formation. To favor cytosine formation,
      reactant concentrations are required that are implausible in a natural setting.
      Furthermore, cytosine is consumed by deamination (the half-life for deamination
      at 25 degrees C is approximately 340 yr) and other reactions. No reactions have
      been described thus far that would produce cytosine, even in a specialized local
      setting, at a rate sufficient to compensate for its decomposition. On the basis
      of this evidence, it appears quite unlikely that cytosine played a role in the
      origin of life. Theories that involve replicators that function without the
      Watson-Crick pairs, or no replicator at all, remain as viable alternatives.

PMID- 10200274
TI  - Two heads of myosin are better than one for generating force and motion.
AB  - Several classes of the myosin superfamily are distinguished by their "double
      headed" structure, where each head is a molecular motor capable of hydrolyzing
      ATP and interacting with actin to generate force and motion. The functional
      significance of this dimeric structure, however, has eluded investigators since
      its discovery in the late 1960s. Using an optical-trap transducer, we have
      measured the unitary displacement and force produced by double-headed and single
      headed smooth- and skeletal-muscle myosins. Single-headed myosin produces
      approximately half the displacement and force (approximately 6 nm; 0.7 pN) of
      double-headed myosin (approximately 10 nm; 1.4 pN) during a unitary interaction
      with actin. These data suggest that muscle myosins require both heads to generate
      maximal force and motion.

PMID- 10200275
TI  - Singular value decomposition with self-modeling applied to determine
      bacteriorhodopsin intermediate spectra: analysis of simulated data.
AB  - An a priori model-independent method for the determination of accurate spectra of
      photocycle intermediates is developed. The method, singular value decomposition
      with self-modeling (SVD-SM), is tested on simulated difference spectra designed
      to mimic the photocycle of the Asp-96 --> Asn mutant of bacteriorhodopsin.
      Stoichiometric constraints, valid until the onset of the recovery of bleached
      bacteriorhodopsin at the end of the photocycle, guide the self-modeling
      procedure. The difference spectra of the intermediates are determined in
      eigenvector space by confining the search for their coordinates to a
      stoichiometric plane. In the absence of random noise, SVD-SM recovers the
      intermediate spectra and their time evolution nearly exactly. The recovery of
      input spectra and kinetics is excellent although somewhat less exact when
      realistic random noise is included in the input spectra. The difference between
      recovered and input kinetics is now visually discernible, but the same reaction
      scheme with nearly identical rate constants to those assumed in the simulation
      fits the output kinetics well. SVD-SM relegates the selection of a photocycle
      model to the late stage of the analysis. It thus avoids derivation of erroneous
      model-specific spectra that result from global model-fitting approaches that
      assume a model at the outset.

PMID- 10200276
TI  - Intermediate spectra and photocycle kinetics of the Asp96 --> asn mutant
      bacteriorhodopsin determined by singular value decomposition with self-modeling.
AB  - Singular value decomposition with self-modeling is applied to resolve the
      intermediate spectra and kinetics of the Asp96 --> Asn mutant bacteriorhodopsin.
      The search for the difference spectra of the intermediates is performed in
      eigenvector space on the stoichiometric plane. The analysis of data at pH values
      ranging from 4 to 8 and temperatures between 5 and 25 degrees C reveals
      significant, early partial recovery of the initial state after photoexcitation.
      The derived spectra are not biased by assumed photocycles. The intermediate
      spectra derived in the initial step differ from spectra determined in prior
      analyses, which results in intermediate concentrations with improved
      stoichiometric properties. Increasingly more accurate photocycles follow with
      increasing assumed complexity, of which parallel models are favored, consistent
      with recent, independent experimental evidence.

PMID- 10200277
TI  - Limiting dynamics of high-frequency electromechanical transduction of outer hair
      cells.
AB  - High-frequency resolution is one of the salient features of peripheral sound
      processing in the mammalian cochlea. The sensitivity originates in the active
      amplification of the travelling wave on the basilar membrane by the outer hair
      cells (OHCs), where electrically induced mechanical action of the OHC on a cycle
      by-cycle basis is believed to be the crucial component. However, it is still
      unclear if this electromechanical action is sufficiently fast and can produce
      enough force to enhance mechanical tuning up to the highest frequencies perceived
      by mammals. Here we show that isolated OHCs in the microchamber configuration are
      able to overcome fluid forces with almost constant displacement amplitude and
      phase up to frequencies well above their place-frequency on the basilar membrane.
      The high-frequency limit of the electromotility, defined as the frequency at
      which the amplitude drops by 3 dB from its asymptotic low-frequency value, is
      inversely dependent on cell length. The frequency limit is at least 79 kHz. For
      frequencies up to 100 kHz, the electromotile response was specified by an
      overdamped (Q = 0.42) second-order resonant system. This finding suggests that
      the limiting factor for frequencies up to 100 kHz is not the speed of the motor
      but damping and inertia. The isometric force produced by the OHC was constant at
      least up to 50 kHz, with amplitudes as high as 53 pN/mV being observed. We
      conclude that the electromechanical transduction process of OHCs possesses the
      necessary high-frequency properties to enable amplification of the travelling
      wave over the entire hearing range.

PMID- 10200278
TI  - Hormone-induced secretory and nuclear translocation of calmodulin: oscillations
      of calmodulin concentration with the nucleus as an integrator.
AB  - Many important enzyme activities are regulated by Ca2+-dependent interactions
      with calmodulin (CaM). Some of the most important targets for CaM action are in
      the nucleus, and Ca2+-dependent CaM translocation into this organelle has been
      reported. Hormone-evoked cytosolic Ca2+ signals occur physiologically as
      oscillations, but, so far, oscillations in CaM concentration have not been
      described. We loaded fluorescent-labeled CaM into pancreatic acinar cells and
      monitored the fluorescence in various regions by confocal microscopy. Sustained
      high concentrations of the hormone cholecystokinin or the neurotransmitter
      acetylcholine evoked a transient movement of cytosolic CaM from the basal
      nonnuclear area into the secretory granule region and, thereafter, a more
      substantial and prolonged translocation of CaM into the nucleoplasm. About 50% of
      the CaM that bound Ca2+ translocated. At a lower hormone concentration, evoking
      Ca2+ oscillations, regular spikes of increased CaM concentration were seen in the
      secretory granule region with mirror image spikes of decreased CaM concentration
      in the basal nonnuclear region. The nucleus was able to integrate the Ca2+ spike
      evoked pulses of CaM translocation into a sustained elevation of the
      nucleoplasmic concentration of this protein.

PMID- 10200279
TI  - Tamoxifen inhibits acidification in cells independent of the estrogen receptor.
AB  - Tamoxifen has been reported to have numerous physiological effects that are
      independent of the estrogen receptor, including sensitization of resistant tumor
      cells to many chemotherapeutic agents. Drug-resistant cells sequester weak base
      chemotherapeutics in acidic organelles away from their sites of action in the
      cytosol and nucleus. This work reports that tamoxifen causes redistribution of
      weak base chemotherapeutics from acidic organelles to the nucleus in drug
      resistant cells. Agents that disrupt organelle acidification (e.g., monensin,
      bafilomycin A1) cause a similar redistribution. Measurement of cellular pH in
      several cell lines reveals that tamoxifen inhibits acidification of endosomes and
      lysosomes without affecting cytoplasmic pH. Similar to monensin, tamoxifen
      decreased the rate of vesicular transport though the recycling and secretory
      pathways. Organellar acidification is required for many cellular functions, and
      its disruption could account for many of the side effects of tamoxifen.

PMID- 10200280
TI  - Protein phosphatase 2A interacts with the 70-kDa S6 kinase and is activated by
      inhibition of FKBP12-rapamycinassociated protein.
AB  - The FKBP12-rapamycin-associated protein (FRAP; also called RAFT1/mTOR) regulates
      translation initiation and entry into the cell cycle. Depriving cells of amino
      acids or treating them with the small molecule rapamycin inhibits FRAP and
      results in rapid dephosphorylation and inactivation of the translational
      regulators 4E-BP1(eukaryotic initiation factor 4E-binding protein 1) and p70(s6k)
      (the 70-kDa S6 kinase). Data published recently have led to the view that FRAP
      acts as a traditional mitogen-activated kinase, directly phosphorylating 4E-BP1
      and p70(s6k) in response to mitogenic stimuli. We present evidence that FRAP
      controls 4E-BP1 and p70(s6k) phosphorylation indirectly by restraining a
      phosphatase. A calyculin A-sensitive phosphatase is required for the rapamycin-
      or amino acid deprivation-induced dephosphorylation of p70(s6k), and treatment of
      Jurkat I cells with rapamycin increases the activity of the protein phosphatase
      2A (PP2A) toward 4E-BP1. PP2A is shown to associate with p70(s6k) but not with a
      mutated p70(s6k) that is resistant to rapamycin- and amino acid deprivation
      mediated dephosphorylation. FRAP also is shown to phosphorylate PP2A in vitro,
      consistent with a model in which phosphorylation of PP2A by FRAP prevents the
      dephosphorylation of 4E-BP1 and p70(s6k), whereas amino acid deprivation or
      rapamycin treatment inhibits FRAP's ability to restrain the phosphatase.

PMID- 10200281
TI  - Thyroid hormone, T3-dependent phosphorylation and translocation of Trip230 from
      the Golgi complex to the nucleus.
AB  - Trip230 is a novel coactivator of the thyroid hormone receptor that is negatively
      regulated by the retinoblastoma tumor-suppressor protein. In an examination of
      its subcellular distribution, Trip230 localized predominantly to the vicinity of
      the Golgi instead of the nucleus, as other nuclear hormone receptor coactivators.
      Using a series of deletion mutants, a critical region identified for Golgi area
      targeting coincided with a previously defined thyroid hormone receptor-binding
      domain of Trip230. During cell cycle progression, the expression level of Trip230
      is constant and a significant portion is imported into the nucleus at S phase.
      Within an hour of treating cells with T3, Trip230 immunofluorescence transiently
      colocalized with TR in prominent subnuclear structures. T3-dependent nuclear
      import of Trip230 does not require new protein synthesis. Coincident with T3
      treatment and nuclear import, newly phosphorylated residue(s) appeared in
      Trip230, suggesting that phosphorylation may be involved in its nuclear import.
      These findings provided a novel mechanism for the regulation of nuclear hormone
      transcription factors by hormone-responsive phosphorylation and nuclear import of
      cytoplasmically located coactivators.

PMID- 10200282
TI  - Mice that lack the angiogenesis inhibitor, thrombospondin 2, mount an altered
      foreign body reaction characterized by increased vascularity.
AB  - Disruption of the thrombospondin 2 gene (Thbs2) in mice results in a complex
      phenotype characterized chiefly by abnormalities in fibroblasts, connective
      tissues, and blood vessels. Consideration of this phenotype suggested to us that
      the foreign body reaction (FBR) might be altered in thrombospondin 2 (TSP2)-null
      mice. To investigate the participation of TSP2 in the FBR, polydimethylsiloxane
      (PDMS) and oxidized PDMS (ox-PDMS) disks were implanted in TSP2-null and control
      mice. Growth of TSP2-null and control skin fibroblasts in vitro also was
      evaluated on both types of disks. Normal fibroblasts grew as a monolayer on both
      surfaces, but attachment of the cells to ox-PDMS was weak and sensitive to
      movement. TSP2-null fibroblasts grew as aggregates on both surfaces, and their
      attachment was further compromised on ox-PDMS. After a 4-week implantation
      period, both types of PDMS elicited a similar FBR with a collagenous capsule in
      both TSP2-null and control mice. However, strikingly, the collagenous capsule
      that formed in TSP2-null mice was highly vascularized and thicker than that
      formed in normal mice. In addition, abnormally shaped collagen fibers were
      observed in capsules from mutant mice. These observations indicate that the
      presence or absence of an extracellular matrix component, TSP2, can influence the
      nature of the FBR, in particular its vascularity. The expression of TSP2
      therefore could represent a molecular target for local inhibitory measures when
      vascularization of the tissue surrounding an implanted device is desired.

PMID- 10200283
TI  - A mouse model for achondroplasia produced by targeting fibroblast growth factor
      receptor 3.
AB  - Achondroplasia, the most common form of dwarfism in man, is a dominant genetic
      disorder caused by a point mutation (G380R) in the transmembrane region of
      fibroblast growth factor receptor 3 (FGFR3). We used gene targeting to introduce
      the human achondroplasia mutation into the murine FGFR3 gene. Heterozygotes for
      this point mutation that carried the neo cassette were normal whereas neo+
      homozygotes had a phenotype similar to FGFR3-deficient mice, exhibiting bone
      overgrowth. This was because of interference with mRNA processing in the presence
      of the neo cassette. Removal of the neo selection marker by Cre/loxP
      recombination yielded a dominant dwarf phenotype. These mice are distinguished by
      their small size, shortened craniofacial area, hypoplasia of the midface with
      protruding incisors, distorted brain case with anteriorly shifted foramen magnum,
      kyphosis, and narrowed and distorted growth plates in the long bones, vertebrae,
      and ribs. These experiments demonstrate that achondroplasia results from a gain
      of-FGFR3-function leading to inhibition of chondrocyte proliferation. These
      achondroplastic dwarf mice represent a reliable and useful model for developing
      drugs for potential treatment of the human disease.

PMID- 10200285
TI  - Environmental variation shapes sexual dimorphism in red deer.
AB  - Sexual dimorphism results from dichotomous selection on male and female
      strategies of growth in relation to reproduction. In polygynous mammals, these
      strategies reflect sexual selection on males for access to females and
      competitive selection on females for access to food. Consequently, in such
      species, males display rapid early growth to large adult size, whereas females
      invest in condition and early sexual maturity at the expense of size. Hence, the
      magnitude of adult size dimorphism should be susceptible to divergence of the
      sexes in response to environmental factors differentially influencing their
      growth to reproduction. We show that divergent growth of male and female red deer
      after 32 years of winter warming and 15 years of contemporaneously earlier plant
      phenology support this prediction. In response to warmer climate during their
      early development, males grew more rapidly and increased in size, while female
      size declined. Conversely, females, but not males, responded to earlier plant
      phenology with increased investment in condition and earlier reproduction.
      Accordingly, adult size dimorphism increased in relation to warmer climate,
      whereas it declined in relation to forage quality. Thus, the evolutionary
      trajectories of growth related to reproduction in the sexes (i) originate from
      sexual and competitive selection, (ii) produce sexual size dimorphism, and (iii)
      are molded by environmental variation.

PMID- 10200284
TI  - Bicoid functions without its TATA-binding protein-associated factor interaction
      domains.
AB  - Four maternal systems are known to pattern the early Drosophila embryo. The key
      component of the anterior system is the homeodomain protein Bicoid (Bcd). Bcd
      needs the contribution of another anterior morphogen, Hunchback (Hb), to function
      properly: Bcd and Hb synergize to organize anterior development. A molecular
      mechanism for this synergy has been proposed to involve specific interactions of
      Bcd and Hb with TATA-binding protein-associated factors (TAFIIs) that are
      components of the general transcription machinery. Bcd contains three putative
      activation domains: a glutamine-rich region, which interacts in vitro with
      TAFII110; an alanine-rich domain, which targets TAFII60; and a C-terminal acidic
      region, which has an unknown role. We have generated flies carrying bcd
      transgenes lacking one or several of these domains to test their function in
      vivo. Surprisingly, a bcd transgene that lacks all three putative activation
      domains is able to rescue the bcdE1 null phenotype to viability. Moreover, the
      development of these embryos is not affected by the presence of dominant negative
      mutations in TAFII110 or TAFII60. This means that the interactions observed in
      vitro between Bcd and TAFII60 or TAFII110 aid transcriptional activation but are
      dispensable for normal development.

PMID- 10200286
TI  - Scaling in animal group-size distributions.
AB  - An elementary model of animal aggregation is presented. The group-size
      distributions resulting from this model are truncated power laws. The predictions
      of the model are found to be consistent with data that describe the group-size
      distributions of tuna fish, sardinellas, and African buffaloes.

PMID- 10200287
TI  - A tradeoff between immunocompetence and sexual ornamentation in domestic fowl.
AB  - Females often select their mates on the basis of the size or intensity of sexual
      ornaments, and it is thought that such traits are reliable indicators of male
      quality because the costliness of these traits prevents cheating. The
      immunocompetence handicap hypothesis is a recently proposed mechanistic
      explanation of these costs and states that males carry ornaments at the expense
      of their resistance to disease and parasites. The tradeoff between
      immunocompetence and sexual ornamentation was hypothesized to arise as a
      consequence of the dual effect of androgens on ornamentation (+) and immune
      function (-). To test this hypothesis, we compared comb size between male
      domestic chickens Gallus domesticus of lines divergently selected for antibody
      responses to sheep erythrocytes (three lines: selected for low response or high
      response and a control line). The importance of comb size in inter- and
      intrasexual selection is well established, and comb size is strongly dependent on
      testosterone level. Comb size was larger in the males of the low line than in the
      high line, and comb size of control males was intermediate, indicating a tradeoff
      between ornamentation and immunocompetence. Testosterone (T) levels varied in a
      similar fashion (TLow > TControl > THigh), suggesting that this hormone could
      mediate the tradeoff between ornamentation and immunocompetence. These results
      support the idea that a tradeoff with immune function may constrain the
      expression of secondary sexual ornaments.

PMID- 10200288
TI  - Expression pattern and, surprisingly, gene length shape codon usage in
      Caenorhabditis, Drosophila, and Arabidopsis.
AB  - We measured the expression pattern and analyzed codon usage in 8,133, 1,550, and
      2,917 genes, respectively, from Caenorhabditis elegans, Drosophila melanogaster,
      and Arabidopsis thaliana. In those three species, we observed a clear correlation
      between codon usage and gene expression levels and showed that this correlation
      is not due to a mutational bias. This provides direct evidence for selection on
      silent sites in those three distantly related multicellular eukaryotes.
      Surprisingly, there is a strong negative correlation between codon usage and
      protein length. This effect is not due to a smaller size of highly expressed
      proteins. Thus, for a same-expression pattern, the selective pressure on codon
      usage appears to be lower in genes encoding long rather than short proteins. This
      puzzling observation is not predicted by any of the current models of selection
      on codon usage and thus raises the question of how translation efficiency affects
      fitness in multicellular organisms.

PMID- 10200289
TI  - Genetic dissection of protein-protein interactions in multi-tRNA synthetase
      complex.
AB  - Cytoplasmic aminoacyl-tRNA synthetases of higher eukaryotes acquired extra
      peptides in the course of their evolution. It has been thought that these
      appendices are related to the occurrence of the multiprotein complex consisting
      of at least eight different tRNA synthetase polypeptides. This complex is
      believed to be a signature feature of metazoans. In this study, we used multiple
      sequence alignments to infer the locations of the peptide appendices from human
      cytoplasmic tRNA synthetases found in the multisynthetase complex. The selected
      peptide appendices ranged from 22 aa of aspartyl-tRNA synthetase to 267 aa of
      methionyl-tRNA synthetase. We then made genetic constructions to investigate
      interactions between all 64 combinations of these peptides that were individually
      fused to nonsynthetase test proteins. The analyses identified 11 (10 heterologous
      and 1 homologous) interactions. The six peptide-dependent interactions paralleled
      what had been detected by crosslinking methods applied to the isolated
      multisynthetase complex. Thus, small peptide appendices seem to link together
      different synthetases into a complex. In addition, five interacting pairs that
      had not been detected previously were suggested from the observed peptide
      dependent complexes.

PMID- 10200290
TI  - Comparative genomic hybridization, loss of heterozygosity, and DNA sequence
      analysis of single cells.
AB  - A PCR strategy is described for global amplification of DNA from a single
      eukaryotic cell that enables the comprehensive analysis of the whole genome. By
      comparative genomic hybridization, not only gross DNA copy number variations,
      such as monosomic X and trisomic 21 in single male cells and cells from Down's
      syndrome patients, respectively, but multiple deletions and amplifications
      characteristic for human tumor cells are reliably retrieved. As a model of
      heterogeneous cell populations exposed to selective pressure, we have studied
      single micrometastatic cells isolated from bone marrow of cancer patients. The
      observed congruent pattern of comparative genomic hybridization data, loss of
      heterozygosity, and mutations as detected by sequencing attests to the
      technique's fidelity and demonstrates its usefulness for assessing clonal
      evolution of genetic variants in complex populations.

PMID- 10200291
TI  - Identification by UV resonance Raman spectroscopy of an imino tautomer of 5
      hydroxy-2'-deoxycytidine, a powerful base analog transition mutagen with a much
      higher unfavored tautomer frequency than that of the natural residue 2'
      deoxycytidine.
AB  - UV resonance Raman spectroscopy was used to detect and estimate the frequency of
      the unfavored imino tautomer of the transition mutagen 5-hydroxy-2'-deoxycytidine
      (HO5dCyt) in its anionic form. In DNA, this 2'-deoxycytidine analog arises from
      the oxidation of 2'-deoxycytidine and induces C --> T transitions with 10(2)
      greater frequency than such spontaneous transitions. An imino tautomer marker
      carbonyl band (approximately 1650 cm-1) is enhanced at approximately 65 degrees C
      against an otherwise stable spectrum of bands associated with the favored amino
      tautomer. This band is similarly present in the UV resonance Raman spectra of the
      imino cytidine analogs N3-methylcytidine at high pH and N4-methoxy-2'
      deoxycytidine at pH 7 and displays features attributable to the imino form of C
      residues and their derivatives. The fact that the imino tautomer of HO5dCyt
      occurs at a frequency consistent with its high mutagenic enhancement lends strong
      support to the hypothesis that unfavored base tautomers play important roles in
      the mispair intermediates of replication leading to substitution mutations.

PMID- 10200292
TI  - High recombination rate in natural populations of Plasmodium falciparum.
AB  - Malaria parasites are sexually reproducing protozoa, although the extent of
      effective meiotic recombination in natural populations has been debated. If
      meiotic recombination occurs frequently, compared with point mutation and mitotic
      rearrangement, linkage disequilibrium between polymorphic sites is expected to
      decline with increasing distance along a chromosome. The rate of this decline
      should be proportional to the effective meiotic recombination rate in the
      population. Multiple polymorphic sites covering a 5-kb region of chromosome 9
      (the msp1 gene) have been typed in 547 isolates from six populations in Africa to
      test for such a decline and estimate its rate in populations of Plasmodium
      falciparum. The magnitude of two-site linkage disequilibrium declines markedly
      with increasing molecular map distance between the sites, reaching nonsignificant
      levels within a map range of 0.3-1.0 kb in five of the populations and over a
      larger map distance in the population with lowest malaria endemicity. The rate of
      decline in linkage disequilibrium over molecular map distance is at least as
      rapid as that observed in most chromosomal regions of other sexually reproducing
      eukaryotes, such as humans and Drosophila. These results are consistent with the
      effective recombination rate expected in natural populations of P. falciparum,
      predicted on the basis of the underlying molecular rate of meiotic crossover and
      the coefficient of inbreeding caused by self-fertilization events. This is
      conclusive evidence to reject any hypothesis of clonality or low rate of meiotic
      recombination in P. falciparum populations. Moreover, the data have major
      implications for the design and interpretation of population genetic studies of
      selection on P. falciparum genes.

PMID- 10200293
TI  - Mucosal vaccination overcomes the barrier to recombinant vaccinia immunization
      caused by preexisting poxvirus immunity.
AB  - Overcoming preexisting immunity to vaccinia virus in the adult population is a
      key requirement for development of otherwise potent recombinant vaccinia
      vaccines. Based on our observation that s.c. immunization with vaccinia induces
      cellular and antibody immunity to vaccinia only in systemic lymphoid tissue and
      not in mucosal sites, we hypothesized that the mucosal immune system remains
      naive to vaccinia and therefore amenable to immunization with recombinant
      vaccinia vectors despite earlier vaccinia exposure. We show that mucosal
      immunization of vaccinia-immune BALB/c mice with recombinant vaccinia expressing
      HIV gp160 induced specific serum antibody and strong HIV-specific cytotoxic T
      lymphocyte responses. These responses occurred not only in mucosal but also in
      systemic lymphoid tissue, whereas systemic immunization was ineffective under
      these circumstances. In this context, intrarectal immunization was more effective
      than intranasal immunization. Boosting with a second dose of recombinant vaccinia
      was also more effective via the mucosal route. The systemic HIV-specific
      cytotoxic T lymphocyte response was enhanced by coadministration of IL-12 at the
      mucosal site. These results also demonstrate the independent compartmentalization
      of the mucosal versus systemic immune systems and the asymmetric trafficking of
      lymphocytes between them. This approach to circumvent previous vaccinia immunity
      may be useful for induction of protective immunity against infectious diseases
      and cancer in the sizable populations with preexisting immunity to vaccinia from
      smallpox vaccination.

PMID- 10200294
TI  - A novel lipopolysaccharide-induced transcription factor regulating tumor necrosis
      factor alpha gene expression: molecular cloning, sequencing, characterization,
      and chromosomal assignment.
AB  - Lipopolysaccharide (LPS) is a potent stimulator of monocytes and macrophages,
      causing secretion of tumor necrosis factor alpha (TNF-alpha) and other
      inflammatory mediators. Given the deleterious effects to the host of TNF-alpha,
      it has been postulated that TNF-alpha gene expression must be tightly regulated.
      The nature of the nuclear factor(s) that control TNF-alpha gene transcription in
      humans remains obscure, although NF-kappaB has been suggested. Our previous
      studies pertaining to macrophage response to LPS identified a novel DNA-binding
      domain located from -550 to -487 in the human TNF-alpha promoter that contains
      transcriptional activity, but lacks any known NF-kappaB-binding sites. We have
      used this DNA fragment to isolate and purify a 60-kDa protein binding to this
      fragment and obtained its amino-terminal sequence, which was used to design
      degenerate probes to screen a cDNA library from THP-1 cells. A novel cDNA clone
      (1.8 kb) was isolated and fully sequenced. Characterization of this cDNA clone
      revealed that its induction was dependent on LPS activation of THP-1 cells;
      hence, the name LPS-induced TNF-alpha factor (LITAF). Inhibition of LITAF mRNA
      expression in THP-1 cells resulted in a reduction of TNF-alpha transcripts. In
      addition, high level of expression of LITAF mRNA was observed predominantly in
      the placenta, peripheral blood leukocytes, lymph nodes, and the spleen. Finally,
      chromosomal localization using fluorescence in situ hybridization revealed that
      LITAF mapped to chromosome 16p12-16p13.3. Together, these findings suggest that
      LITAF plays an important role in the activation of the human TNF-alpha gene and
      proposes a new mechanism to control TNF-alpha gene expression.

PMID- 10200295
TI  - Prevention of collagen-induced arthritis in mice by a polyphenolic fraction from
      green tea.
AB  - Identification of common dietary substances capable of affording protection or
      modulating the onset and severity of arthritis may have important human health
      implications. An antioxidant-rich polyphenolic fraction isolated from green tea
      (green tea polyphenols, GTPs) has been shown to possess anti-inflammatory and
      anticarcinogenic properties in experimental animals. In this study we determined
      the effect of oral consumption of GTP on collagen-induced arthritis in mice. In
      three independent experiments mice given GTP in water exhibited significantly
      reduced incidence of arthritis (33% to 50%) as compared with mice not given GTP
      in water (84% to 100%). The arthritis index also was significantly lower in GTP
      fed animals. Western blot analysis showed a marked reduction in the expression of
      inflammatory mediators such as cyclooxygenase 2, IFN-gamma, and tumor necrosis
      factor alpha in arthritic joints of GTP-fed mice. Histologic and
      immunohistochemical analysis of the arthritic joints in GTP-fed mice demonstrated
      only marginal joint infiltration by IFN-gamma and tumor necrosis factor alpha
      producing cells as opposed to massive cellular infiltration and fully developed
      pannus in arthritic joints of non-GTP-fed mice. The neutral endopeptidase
      activity was approximately 7-fold higher in arthritic joints of non-GTP-fed mice
      in comparison to nonarthritic joints of unimmunized mice whereas it was only 2
      fold higher in the arthritic joints of GTP-fed mice. Additionally, total IgG and
      type II collagen-specific IgG levels were lower in serum and arthritic joints of
      GTP-fed mice. Taken together our studies suggest that a polyphenolic fraction
      from green tea that is rich in antioxidants may be useful in the prevention of
      onset and severity of arthritis.

PMID- 10200297
TI  - Millimeter-scale positioning of a nerve-growth-factor source and biological
      activity in the brain.
AB  - Toxicity prevents the systemic administration of many therapeutic proteins, and
      attempts at protein targeting via the circulatory system (i.e., "magic bullets")
      have failed in all but a few special cases. Direct administration at the target
      site is a logical alternative, particularly in the central nervous system, but
      the limits of direct administration have not been defined clearly. Nerve growth
      factor (NGF) enhances survival of cholinergic neurons and, therefore, has
      generated considerable interest for the treatment of Alzheimer's disease. We
      tested the effectiveness of local delivery by implanting small polymer pellets
      that slowly released NGF into the central nervous system of adult rats at
      controlled distances from a target site containing transplanted fetal cholinergic
      cells. NGF-releasing implants placed within 1-2 mm of the treatment site enhanced
      the biological function of cellular targets, whereas identical implants placed
      approximately 3 mm from the target site of treatment produced no beneficial
      effect. Effective NGF therapy required millimeter-scale positioning of the NGF
      source, and efficacy correlated with the spatial distribution of NGF
      concentration in the tissue; this result suggests that NGF must be delivered
      within several millimeters of the target to be effective in treating Alzheimer's
      disease. Because the human brain is divided into functional regions that are
      typically several centimeters in diameter and often irregular in shape, new
      methods for sculpting larger-scale drug fields are needed. We illustrate a
      concept, called pharmacotectonics, in which drug-delivery systems are arranged
      spatially in tissues to shape concentration fields for potent agents.

PMID- 10200296
TI  - Reconstitution of functional L-selectin ligands on a cultured human endothelial
      cell line by cotransfection of alpha1-->3 fucosyltransferase VII and newly cloned
      GlcNAcbeta:6-sulfotransferase cDNA.
AB  - Recently, we proposed sialyl 6-sulfo Lewis X as a major carbohydrate-capping
      group of the L-selectin ligands on high endothelial venules in human lymph nodes.
      In this study we succeeded in reconstituting functional L-selectin ligands on a
      cultured human endothelial cell line, ECV304, by transfecting the alpha1-
      >3fucosyltranseferase VII (Fuc-T VII) and newly cloned GlcNAcbeta:6
      sulfotransferase (6-Sul-T) cDNAs. The ECV304 cells transfected with Fuc-T VII
      cDNA expressed conventional sialyl Lewis X detected with specific antibodies
      including 2H5, whereas the cells transfected with 6-Sul-T cDNA expressed sialyl 6
      sulfo lactosamine as well as MECA-79-defined carbohydrate determinants, but these
      singly transfected cells failed to express sialyl 6-sulfo Lewis X, as detected
      with the antisialyl 6-sulfo Lewis X mAb G152. Sialyl 6-sulfo Lewis X appeared
      only on the cells that were cotransfected with both 6-Sul-T and Fuc-T VII cDNAs.
      Significant adhesion of L-selectin-expressing cells was seen only to the doubly
      transfected ECV304 cells and was inhibited by G152. No adhesion was observed to
      the cells transfected either with 6-Sul-T or with Fuc-T VII cDNA alone. The mRNAs
      of the two enzymes were expressed or were inducible upon interleukin 1
      stimulation in human endothelial cells. These results indicate that a set of
      carbohydrate determinants synthesized by the concerted action of the two enzymes,
      as typically represented by the sialyl 6-sulfo Lewis X-capping group, serves as
      an essential component of the ligand for L-selectin and that the reagents 2H5 and
      MECA-79, utilized in earlier studies to detect L-selectin ligand on high
      endothelial venules, recognize two different aspects of the same set of synthetic
      products.

PMID- 10200298
TI  - Roles of trk family neurotrophin receptors in medullary thyroid carcinoma
      development and progression.
AB  - Although initiating mutations in the ret protooncogene have been found in
      familial and sporadic medullary thyroid carcinoma (MTC), the molecular events
      underlying subsequent tumor progression stages are unknown. We now report that
      changes in trk family neurotrophin receptor expression appear to be involved in
      both preneoplastic thyroid C cell hyperplasia and later tumor progression. Only a
      subset of normal C cells expresses trk family receptors, but, in C cell
      hyperplasia, the affected cells consistently express trkB, with variable
      expression of trkA and trkC. In later stages of gross MTC tumors, trkB expression
      was substantially reduced, while trkC expression was increased and often intense.
      In a cell culture model of MTC, exogenous trkB expression resulted in severely
      impaired tumorigenicity and was associated with 11-fold lower levels of the
      angiogenesis factor vascular endothelial growth factor. These results suggest
      that trk family receptor genes participate in MTC development and progression,
      and, in particular, that trkB may limit MTC tumor growth by inhibition of
      angiogenesis.

PMID- 10200300
TI  - Defective CD95/APO-1/Fas signal complex formation in the human autoimmune
      lymphoproliferative syndrome, type Ia.
AB  - Heterozygous mutations in the CD95 (APO-1/Fas) receptor occur in most individuals
      with autoimmune lymphoproliferative syndrome (ALPS) and dominantly interfere with
      apoptosis by an unknown mechanism. We show that local or global alterations in
      the structure of the cytoplasmic death domain from nine independent ALPS CD95
      death-domain mutations result in a failure to bind the FADD/MORT1 signaling
      protein. Despite heterozygosity for the abnormal allele, lymphocytes from ALPS
      patients showed markedly decreased FADD association and a loss of caspase
      recruitment and activation after CD95 crosslinking. These data suggest that
      intracytoplasmic CD95 mutations in ALPS impair apoptosis chiefly by disrupting
      death-domain interactions with the signaling protein FADD/MORT1.

PMID- 10200299
TI  - Distribution of human herpesvirus-8 latently infected cells in Kaposi's sarcoma,
      multicentric Castleman's disease, and primary effusion lymphoma.
AB  - Human herpesvirus 8 (HHV-8, also called KSHV) is linked to the etiopathogenesis
      of Kaposi's sarcoma (KS), multicentric Castleman's disease (MCD), and primary
      effusion lymphoma (PEL). The universal presence of HHV-8 in early KS has not yet
      been shown. We used a mAb (LN53) against latent nuclear antigen-1 (LNA-1) of HHV
      8 encoded by ORF73 to study the distribution of the cell types latently infected
      by HHV-8 in patch, plaque, and nodular KS, MCD, and PEL. In early KS, HHV-8 is
      present in <10% of cells forming the walls of ectatic vessels. In nodular KS, HHV
      8 is present in cells surrounding slit-like vessels and in >90% of spindle cells,
      but not in normal vascular endothelium. In addition, HHV-8 colocalizes with
      vascular endothelial growth factor receptor-3 (VEGFR-3), a marker of lymphatic
      and precursor endothelium. In early KS lesions, VEGFR-3 is more extensively
      expressed than LNA-1, indicating that HHV-8 is not inducing the proliferation of
      VEGFR-3-positive endothelium directly. In MCD, HHV-8 is present in mantle zone
      large immunoblastic B cells. No staining for LNA-1 is seen in samples from
      multiple myeloma, prostate cancer, and angiosarcoma, supporting the absence of
      any etiological link between these diseases and HHV-8.

PMID- 10200301
TI  - Hypervariable region 3 residues of HIV type 1 gp120 involved in CCR5 coreceptor
      utilization: therapeutic and prophylactic implications.
AB  - Crystallographic characterization of a ternary complex containing a monomeric
      gp120 core, parts of CD4, and a mAb, revealed a region that bridges the inner and
      outer domains of gp120. In a related genetic study, several residues conserved
      among primate lentiviruses were found to play important roles in CC-chemokine
      receptor 5 (CCR5) coreceptor utilization, and all but one were mapped to the
      bridging domain. To reconcile this finding with previous reports that the
      hypervariable region 3 (V3) of gp120 plays an important role in chemokine
      coreceptor utilization, elucidating the roles of various V3 residues in this
      critical part of the HIV type 1 (HIV-1) life cycle is essential. Alanine-scanning
      mutagenesis was carried out to identify V3 residues critical for CCR5
      utilization. Our findings demonstrated that several residues in V3 were critical
      to CCR5 utilization. Furthermore, these residues included not only those
      conserved across HIV-1 subtypes, but also those that varied among HIV-1 subtypes.
      Although the highly conserved V3 residues may represent unique targets for
      antiviral designs, the involvement of variable residues raises the possibility
      that antigenic variation in the coreceptor binding domain could further
      complicate HIV-1 vaccine design.

PMID- 10200302
TI  - Virulence and transmission success of the malarial parasite Plasmodium
      falciparum.
AB  - Virulence of Plasmodium falciparum is associated with the expression of variant
      surface antigens designated PfEMP1 (P. falciparum erythrocyte membrane protein 1)
      that are encoded by a family of var genes. Data presented show that the
      transmission stages of P. falciparum also express PfEMP1 variants. Virulence in
      this host-parasite system can be considered a variable outcome of optimizing the
      production of sexual transmission stages from the population of disease-inducing
      asexual stages. Immunity to PfEMP1 will contribute to the regulation of this
      trade-off by controlling the parasite population with potential to produce mature
      transmission stages.

PMID- 10200303
TI  - Neuroanatomical correlates of hunger and satiation in humans using positron
      emission tomography.
AB  - The central role of the hypothalamus in the origination and/or processing of
      feeding-related stimuli may be modulated by the activity of other functional
      areas of the brain including the insular cortex (involved in enteroceptive
      monitoring) and the prefrontal cortex (involved in the inhibition of
      inappropriate response tendencies). Regional cerebral blood flow (rCBF), a marker
      of neuronal activity, was measured in 11 healthy, normal-weight men by using
      positron emission tomography in a state of hunger (after 36-h fast) and a state
      of satiation (after a liquid meal). Hunger was associated with significantly
      increased rCBF in the vicinity of the hypothalamus and insular cortex and in
      additional paralimbic and limbic areas (orbitofrontal cortex, anterior cingulate
      cortex, and parahippocampal and hippocampal formation), thalamus, caudate,
      precuneus, putamen, and cerebellum. Satiation was associated with increased rCBF
      in the vicinity of the ventromedial prefrontal cortex, dorsolateral prefrontal
      cortex, and inferior parietal lobule. Changes in plasma insulin concentrations in
      response to the meal were negatively correlated with changes in rCBF in the
      insular and orbitofrontal cortex. Changes in plasma free fatty acid
      concentrations in response to the meal were negatively correlated with changes in
      rCBF in the anterior cingulate and positively correlated with changes in rCBF in
      the dorsolateral prefrontal cortex. In conclusion, these findings raise the
      possibility that several regions of the brain participate in the regulation of
      hunger and satiation and that insulin and free fatty acids may be metabolic
      modulators of postprandial brain neuronal events. Although exploratory, the
      present study provides a foundation for investigating the human brain regions and
      cognitive operations that respond to nutritional stimuli.

PMID- 10200304
TI  - A 500-bp region, approximately 40 kb upstream of the human CYP19 (aromatase)
      gene, mediates placenta-specific expression in transgenic mice.
AB  - In humans, aromatase P450 (product of CYP19 gene), which catalyzes conversion of
      C19 steroids to estrogens, is expressed in a number of tissues, including ovary,
      adipose, and syncytiotrophoblast of the placenta. The 5' untranslated regions of
      CYP19 mRNA transcripts in these tissues are encoded by different tissue-specific
      first exons, which are spliced onto a common site just upstream of the
      translation initiation site in exon II. In placenta, the 5' untranslated region
      of CYP19 mRNA transcripts is encoded by exon I.1, which lies approximately 40 kb
      upstream of exon II. To map genomic sequences required for placenta-specific
      CYP19 expression, fusion genes containing 2,400 and 501 bp of placenta-specific
      exon I.1 5' flanking DNA linked to the human growth hormone gene (hGH), as
      reporter, were introduced into transgenic mice. Expression of CYP19(I.1):hGH
      fusion genes containing as little as 501 bp of 5' flanking DNA was placenta
      specific and developmentally regulated. Furthermore, transgene expression
      occurred specifically in the labyrinthine trophoblast of the mouse placenta,
      which contains syncytial cells that may be analogous to the human
      syncytiotrophoblast. We show that a relatively small segment of DNA
      (approximately 500 bp) >40 kb upstream of the protein coding region of a human
      gene is able to direct expression in an appropriate tissue- and cell-specific
      manner in transgenic mice. These findings suggest that 5' flanking DNA within 501
      bp of exon I.1 of the human CYP19 gene contains cis-acting elements that bind
      placenta-specific transcription factors that are conserved between humans and
      mice.

PMID- 10200305
TI  - Polymorphism in RANTES chemokine promoter affects HIV-1 disease progression.
AB  - RANTES (regulated on activation normal T cell expressed and secreted) is one of
      the natural ligands for the chemokine receptor CCR5 and potently suppresses in
      vitro replication of the R5 strains of HIV-1, which use CCR5 as a coreceptor.
      Previous studies showed that peripheral blood mononuclear cells or CD4(+)
      lymphocytes obtained from different individuals had wide variations in their
      ability to secrete RANTES. These findings prompted us to analyze the upstream
      noncoding region of the RANTES gene, which contains cis-acting elements involved
      in RANTES promoter activity, in 272 HIV-1-infected and 193 non-HIV-1-infected
      individuals in Japan. Our results showed that there were two polymorphic
      positions, one of which was associated with reduced CD4(+) lymphocyte depletion
      rates during untreated periods in HIV-1-infected individuals. This mutation,
      RANTES-28G, occurred at an allele frequency of approximately 17% in the non-HIV-1
      infected Japanese population and exerted no influence on the incidence of HIV-1
      infection. Functional analyses of RANTES promoter activity indicated that the
      RANTES-28G mutation increases transcription of the RANTES gene. Taken together,
      these data suggest that the RANTES-28G mutation increases RANTES expression in
      HIV-1-infected individuals and thus delays the progression of the HIV-1 disease.

PMID- 10200306
TI  - Noninvasive measurement of anatomic structure and intraluminal oxygenation in the
      gastrointestinal tract of living mice with spatial and spectral EPR imaging.
AB  - EPR imaging has emerged as an important tool for noninvasive three-dimensional
      (3D) spatial mapping of free radicals in biological tissues. Spectral-spatial EPR
      imaging enables mapping of the spectral information at each spatial position,
      and, from the observed line width, the localized tissue oxygenation can be
      mapped. We report the development of EPR imaging instrumentation enabling 3D
      spatial and spectral-spatial EPR imaging of small animals. This instrumentation,
      along with the use of a biocompatible charcoal oximetry-probe suspension, enabled
      3D spatial imaging of the gastrointestinal (GI) tract, along with mapping of
      oxygenation in living mice. By using these techniques, the oxygen tension was
      mapped at different levels of the GI tract from the stomach to the rectum. The
      results clearly show the presence of a marked oxygen gradient from the proximal
      to the distal GI tract, which decreases after respiratory arrest. This technique
      for in vivo mapping of oxygenation is a promising method, enabling the
      noninvasive imaging of oxygen within the normal GI tract. This method should be
      useful in determining the alterations in oxygenation associated with disease.

PMID- 10200307
TI  - A synthetic inhibitor of histone deacetylase, MS-27-275, with marked in vivo
      antitumor activity against human tumors.
AB  - Synthetic benzamide derivatives were investigated for their ability to inhibit
      histone deacetylase (HDA). In this study, one of the most active benzamide
      derivatives, MS-27-275, was examined with regard to its biological properties and
      antitumor efficacy. MS-27-275 inhibited partially purified human HDA and caused
      hyperacetylation of nuclear histones in various tumor cell lines. It behaved in a
      manner similar to other HDA inhibitors, such as sodium butyrate and trichostatin
      A; MS-27-275 induced p21(WAF1/CIP1) and gelsolin and changed the cell cycle
      distribution, decrease of S-phase cells, and increase of G1-phase cells. The in
      vitro sensitivity spectrum of MS-27-275 against various human tumor cell lines
      showed a pattern different than that of a commonly used antitumor agent, 5
      fluorouracil, and, of interest, the accumulation of p21(WAF1/CIP1) tended to be
      faster and greater in the cell lines sensitive to MS-27-275. MS-27-275
      administered orally strongly inhibited the growth in seven of eight tumor lines
      implanted into nude mice, although most of these did not respond to 5
      fluorouracil. A structurally analogous compound to MS-27-275 without HDA
      inhibiting activity showed neither the biological effects in cell culture nor the
      in vivo therapeutic efficacy. These results suggest that MS-27-275 acts as an
      antitumor agent through HDA inhibition and may provide a novel chemotherapeutic
      strategy for cancers insensitive to traditional antitumor agents.

PMID- 10200308
TI  - Stable alphavirus packaging cell lines for Sindbis virus and Semliki Forest virus
      derived vectors.
AB  - Alphavirus vectors are being developed for possible human vaccine and gene
      therapy applications. We have sought to advance this field by devising DNA-based
      vectors and approaches for the production of recombinant vector particles. In
      this work, we generated a panel of alphavirus vector packaging cell lines (PCLs).
      These cell lines were stably transformed with expression cassettes that
      constitutively produced RNA transcripts encoding the Sindbis virus structural
      proteins under the regulation of their native subgenomic RNA promoter. As such,
      translation of the structural proteins was highly inducible and was detected only
      after synthesis of an authentic subgenomic mRNA by the vector-encoded replicase
      proteins. Efficient production of biologically active vector particles occurred
      after introduction of Sindbis virus vectors into the PCLs. In one configuration,
      the capsid and envelope glycoproteins were separated into distinct cassettes,
      resulting in vector packaging levels of 10(7) infectious units/ml, but reducing
      the generation of contaminating replication-competent virus below the limit of
      detection. Vector particle seed stocks could be amplified after low multiplicity
      of infection of PCLs, again without generating replication-competent virus,
      suggesting utility for production of large-scale vector preparations.
      Furthermore, both Sindbis virus-based and Semliki Forest virus-based vectors
      could be packaged with similar efficiency, indicating the possibility of
      developing a single PCL for use with multiple alphavirus-derived vectors.

PMID- 10200309
TI  - Self-assembly of polyglutamine-containing huntingtin fragments into amyloid-like
      fibrils: implications for Huntington's disease pathology.
AB  - Huntington's disease is a progressive neurodegenerative disorder caused by a
      polyglutamine [poly(Q)] repeat expansion in the first exon of the huntingtin
      protein. Previously, we showed that N-terminal huntingtin peptides with poly(Q)
      tracts in the pathological range (51-122 glutamines), but not with poly(Q) tracts
      in the normal range (20 and 30 glutamines), form high molecular weight protein
      aggregates with a fibrillar or ribbon-like morphology, reminiscent of scrapie
      prion rods and beta-amyloid fibrils in Alzheimer's disease. Here we report that
      the formation of amyloid-like huntingtin aggregates in vitro not only depends on
      poly(Q) repeat length but also critically depends on protein concentration and
      time. Furthermore, the in vitro aggregation of huntingtin can be seeded by
      preformed fibrils. Together, these results suggest that amyloid fibrillogenesis
      in Huntington's disease, like in Alzheimer's disease, is a nucleation-dependent
      polymerization.

PMID- 10200310
TI  - Escherichia coli genes regulated by cell-to-cell signaling.
AB  - Utilizing the bicistronic reporter transposon mini-Tn5 lacZ-tet/1, we have
      identified lacZ fusions to four Escherichia coli genes/operons that are strongly
      activated by the accumulation of self-produced extracellular signals. These
      fusions were designated cma9, cma48, cma113, and cma114 for conditioned medium
      activated. Each of the cma fusions was expressed in a growth phase-dependent
      manner, and the presence of conditioned medium from a stationary phase E. coli
      culture resulted in the premature activation of these fusions in cells at early
      to mid-logarithmic phase. The cma48 and cma114 fusions were dependent on RpoS for
      growth phase expression and response to extracellular factors. The extracellular
      factors that activated the cma9, cma48, and cma114 fusions were produced in both
      rich complex and defined minimal media. The cma fusions were shown to be within
      the cysK (cma9), astD (cma48), tnaB (cma113), and gabT (cma114) genes. These
      genes function in the uptake, synthesis, or degradation of amino acids that yield
      pyruvate and succinate.

PMID- 10200311
TI  - A corrinoid-dependent catabolic pathway for growth of a Methylobacterium strain
      with chloromethane.
AB  - Methylobacterium sp. strain CM4, an aerobic methylotrophic alpha-proteobacterium,
      is able to grow with chloromethane as a carbon and energy source. Mutants of this
      strain that still grew with methanol, methylamine, or formate, but were unable to
      grow with chloromethane, were previously obtained by miniTn5 mutagenesis. The
      transposon insertion sites in six of these mutants mapped to two distinct DNA
      fragments. The sequences of these fragments, which extended over more than 17 kb,
      were determined. Sequence analysis, mutant properties, and measurements of enzyme
      activity in cell-free extracts allowed the definition of a multistep pathway for
      the conversion of chloromethane to formate. The methyl group of chloromethane is
      first transferred by the protein CmuA (cmu: chloromethane utilization) to a
      corrinoid protein, from where it is transferred to H4folate by CmuB. Both CmuA
      and CmuB display sequence similarity to methyltransferases of methanogenic
      archaea. In its C-terminal part, CmuA is also very similar to corrinoid-binding
      proteins, indicating that it is a bifunctional protein consisting of two domains
      that are expressed as separate polypeptides in methyl transfer systems of
      methanogens. The methyl group derived from chloromethane is then processed by
      means of pterine-linked intermediates to formate by a pathway that appears to be
      distinct from those already described in Methylobacterium. Remarkable features of
      this pathway for the catabolism of chloromethane thus include the involvement of
      a corrinoid-dependent methyltransferase system for dehalogenation in an aerobe
      and a set of enzymes specifically involved in funneling the C1 moiety derived
      from chloromethane into central metabolism.

PMID- 10200312
TI  - Human RNA-specific adenosine deaminase ADAR1 transcripts possess alternative exon
      1 structures that initiate from different promoters, one constitutively active
      and the other interferon inducible.
AB  - RNA-specific adenosine deaminase (ADAR1) catalyzes the deamination of adenosine
      to inosine in viral and cellular RNAs. Two size forms of the ADAR1 editing enzyme
      are known, an IFN-inducible approximately 150-kDa protein and a constitutively
      expressed N-terminally truncated approximately 110-kDa protein. We have now
      identified alternative exon 1 structures of human ADAR1 transcripts that initiate
      from unique promoters, one constitutively expressed and the other IFN inducible.
      Cloning and sequence analyses of 5'-rapid amplification of cDNA ends (RACE) cDNAs
      from human placenta established a linkage between exon 2 of ADAR1 and two
      alternative exon 1 structures, designated herein as exon 1A and exon 1B. Analysis
      of RNA isolated from untreated and IFN-treated human amnion cells demonstrated
      that exon 1B-exon 2 transcripts were synthesized in the absence of IFN and were
      not significantly altered in amount by IFN treatment. By contrast, exon 1A-exon 2
      transcripts were IFN inducible. Transient transfection analysis with reporter
      constructs led to the identification of two functional promoters, designated PC
      and PI. Exon 1B transcripts were initiated from the PC promoter whose activity in
      transient transfection reporter assays was not increased by IFN treatment. The
      107-nt exon 1B mapped 14.5 kb upstream of exon 2. The 201-nt exon 1A that mapped
      5.4 kb upstream of exon 2 was initiated from the interferon-inducible PI
      promoter. These results suggest that two promoters, one IFN inducible and the
      other not, initiate transcription of the ADAR1 gene, and that alternative
      splicing of unique exon 1 structures to a common exon 2 junction generates RNA
      transcripts with the deduced coding capacity for either the constitutively
      expressed approximately 110-kDa ADAR1 protein (exon 1B) or the interferon-induced
      approximately 150-kDa ADAR1 protein (exon 1A).

PMID- 10200313
TI  - An intronic enhancer containing an N-box motif is required for synapse- and
      tissue-specific expression of the acetylcholinesterase gene in skeletal muscle
      fibers.
AB  - mRNAs encoding acetylcholinesterase (AChE; EC 3.1.1.7) are highly concentrated
      within the postsynaptic sarcoplasm of adult skeletal muscle fibers, where their
      expression is markedly influenced by nerve-evoked electrical activity and trophic
      factors. To determine whether transcriptional regulatory mechanisms account for
      the synaptic accumulation of AChE transcripts at the mammalian neuromuscular
      synapse, we cloned a 5.3-kb DNA fragment that contained the 5' regulatory region
      of the rat AChE gene and generated several constructs in which AChE promoter
      fragments were placed upstream of the reporter gene lacZ and a nuclear
      localization signal (nls). Using a recently described transient expression assay
      system in intact skeletal muscle, we show that this AChE promoter fragment
      directs the synapse-specific expression of the reporter gene. Deletion analysis
      revealed that a 499-bp fragment located in the first intron of the AChE gene is
      essential for expression in muscle fibers. Further analysis showed that sequences
      contained within this intronic fragment were (i) functionally independent of
      position and orientation and (ii) inactive in hematopoietic cells. Disruption of
      an N-box motif located within this DNA fragment reduced by more than 80% the
      expression of the reporter gene in muscle fibers. In contrast, mutation of an
      adjacent CArG element had no effect on nlsLacZ expression. Taken together, these
      results indicate that a muscle-specific enhancer is present within the first
      intron of the AChE gene and that an intronic N-box is essential for the
      regulation of AChE along skeletal muscle fibers.

PMID- 10200314
TI  - Evectins: vesicular proteins that carry a pleckstrin homology domain and localize
      to post-Golgi membranes.
AB  - We have identified two vesicular proteins, designated evectin (evt)-1 and -2.
      These proteins are approximately 25 kDa in molecular mass, lack a cleaved N
      terminal signal sequence, and appear to be inserted into membranes through a C
      terminal hydrophobic anchor. They also carry a pleckstrin homology domain at
      their N termini, which potentially couples them to signal transduction pathways
      that result in the production of lipid second messengers. evt-1 is specific to
      the nervous system, where it is expressed in photoreceptors and myelinating glia,
      polarized cell types in which plasma membrane biosynthesis is prodigious and
      regulated; in contrast, evt-2 is widely expressed in both neural and nonneural
      tissues. In photoreceptors, evt-1 localizes to rhodopsin-bearing membranes of the
      post-Golgi, an important transport compartment for which specific molecular
      markers have heretofore been lacking. The structure and subcellular distribution
      of evt-1 strongly implicate this protein as a mediator of post-Golgi trafficking
      in cells that produce large membrane-rich organelles. Its restricted cellular
      distribution and genetic locus make it a candidate gene for the inherited human
      retinopathy autosomal dominant familial exudative vitreoretinopathy and suggest
      that it also may be a susceptibility gene for multiple sclerosis.

PMID- 10200316
TI  - Quantization of continuous arm movements in humans with brain injury.
AB  - Segmentation of apparently continuous movement has been reported for over a
      century by human movement researchers, but the existence of primitive
      submovements has never been proved. In 20 patients recovering from a single
      cerebral vascular accident (stroke), we identified the apparent submovements that
      composed a continuous arm motion in an unloaded task. Kinematic analysis
      demonstrated a submovement speed profile that was invariant across patients with
      different brain lesions and provided experimental verification of the detailed
      shape of primitive submovements. The submovement shape was unaffected by its peak
      speed, and to test further the invariance of shape with speed, we analyzed
      movement behavior in a patient with myoclonus. This patient occasionally made
      involuntary shock-like arm movements, which occurred near the maximum capacity of
      the neuromuscular system, exhibited speed profiles that were comparable to those
      identified in stroke patients, and were also independent of speed.

PMID- 10200315
TI  - Expression of the antiproliferative gene TIS21 at the onset of neurogenesis
      identifies single neuroepithelial cells that switch from proliferative to neuron
      generating division.
AB  - At the onset of mammalian neurogenesis, neuroepithelial (NE) cells switch from
      proliferative to neuron-generating divisions. Understanding the molecular basis
      of this switch requires the ability to distinguish between these two types of
      division. Here we show that in the mouse ventricular zone, expression of the mRNA
      of the antiproliferative gene TIS21 (PC3, BTG2) (i) starts at the onset of
      neurogenesis, (ii) is confined to a subpopulation of NE cells that increases in
      correlation with the progression of neurogenesis, and (iii) is not detected in
      newborn neurons. Expression of the TIS21 mRNA in the NE cells occurs transiently
      during the cell cycle, i.e., in the G1 phase. In contrast to the TIS21 mRNA, the
      TIS21 protein persists through the division of NE cells and is inherited by the
      neurons, where it remains detectable during neuronal migration and the initial
      phase of differentiation. Our observations indicate that the TIS21 gene is
      specifically expressed in those NE cells that, at their next division, will
      generate postmitotic neurons, but not in proliferating NE cells. Using TIS21 as a
      marker, we find that the switch from proliferative to neuron-generating divisions
      is initiated in single NE cells rather than in synchronized neighboring cells.

PMID- 10200317
TI  - A selective role of calcineurin aalpha in synaptic depotentiation in hippocampus.
AB  - Pharmacological studies have suggested that long-term potentiation (LTP) and long
      term depression (LTD) and depotentiation, three forms of synaptic plasticity in
      the hippocampus, require the activity of the phosphatase calcineurin. At least
      two different isoforms of calcineurin are found in the central nervous system. To
      investigate whether all of these forms of synaptic plasticity require the same
      isoforms of calcineurin, we have examined LTD, depotentiation, and LTP in mice
      lacking the predominant calcineurin isoform in the central nervous system, Aalpha
      /- mice. Depotentiation was abolished completely whereas neither LTD nor LTP were
      affected. These studies provide genetic evidence that the Aalpha isoform of
      calcineurin is important for the reversal of LTP in the hippocampus and indicate
      that depotentiation and LTD operate through somewhat different molecular
      mechanisms.

PMID- 10200318
TI  - Genetic background changes the pattern of forebrain commissure defects in
      transgenic mice underexpressing the beta-amyloid-precursor protein.
AB  - We previously have reported corpus callosum defects in transgenic mice expressing
      the beta-amyloid precursor protein (betaAPP) with a deletion of exon 2 and at
      only 5% of normal levels. This finding indicates a possible involvement of
      betaAPP in the regulation or guidance of axon growth during neural development.
      To determine to what degree the betaAPP mutation interacts with genetic
      background alleles that predispose for forebrain commissure defects in some mouse
      lines, we have assessed the size of the forebrain commissures in a sample of 298
      mice. Lines with mixed genetic background were compared with congenic lines
      obtained by backcrossing to the parental strains C57BL/6 and 129/SvEv. Mice
      bearing a null mutation of the betaAPP gene also were included in the analysis.
      We show that, independently of genetic background, both lack and underexpression
      of betaAPP are associated with reduced brain weight and reduced size of forebrain
      commissures, especially of the ventral hippocampal commissure. In addition, both
      mutations drastically increase the frequency and severity of callosal agenesis
      and hippocampal commissure defects in mouse lines with 129/SvEv or 129/Ola
      background.

PMID- 10200319
TI  - An apamin-sensitive Ca2+-activated K+ current in hippocampal pyramidal neurons.
AB  - In hippocampal and other cortical neurons, action potentials are followed by
      afterhyperpolarizations (AHPs) generated by the activation of small-conductance
      Ca2+-activated K+ channels (SK channels). By shaping the neuronal firing pattern,
      these AHPs contribute to the regulation of excitability and to the encoding
      function of neurons. Here we report that CA1 pyramidal neurons express an AHP
      current that is suppressed by apamin and is involved in the control of repetitive
      firing. This current presents distinct kinetic and pharmacological features, and
      it is modulated differently than the apamin-insensitive slow AHP current.
      Furthermore, our in situ hybridizations show that the apamin-sensitive SK
      subunits are expressed in CA1 pyramidal neurons, providing a potential molecular
      correlate to the apamin-sensitive AHP current. Altogether, these results clarify
      the discrepancy between the reported high density of apamin-binding sites in the
      CA1 region and the apparent lack of an apamin-sensitive current in CA1 pyramidal
      neurons, and they may explain the effects of this toxin on hippocampal synaptic
      plasticity and learning.

PMID- 10200320
TI  - Cyclopentenone prostaglandins suppress activation of microglia: down-regulation
      of inducible nitric-oxide synthase by 15-deoxy-Delta12,14-prostaglandin J2.
AB  - Mechanisms leading to down-regulation of activated microglia and astrocytes are
      poorly understood, in spite of the potentially detrimental role of activated glia
      in neurodegeneration. Prostaglandins, produced both by neurons and glia, may
      serve as mediators of glial and neuronal functions. We examined the influence of
      cyclopentenone prostaglandins and their precursors on activated glia. As models
      of glial activation, production of inducible nitric-oxide synthase (iNOS) was
      studied in lipopolysaccharide-stimulated rat microglia, a murine microglial cell
      line BV-2, and IL-1beta-stimulated rat astrocytes. Cyclopentenone prostaglandins
      were potent inhibitors of iNOS induction and were more effective than their
      precursors, prostaglandins E2 and D2. 15-Deoxy-Delta12,14-prostaglandin J2 (15d
      PGJ2) was the most potent prostaglandin among those tested. In activated
      microglia, 15d-PGJ2 suppressed iNOS promoter activity, iNOS mRNA, and protein
      levels. The action of 15d-PGJ2 does not appear to involve its nuclear receptor
      peroxisome proliferator-activated receptor gamma (PPARgamma) because
      troglitazone, a specific ligand of PPARgamma, was unable to inhibit iNOS
      induction, and neither troglitazone nor 15d-PGJ2 could stimulate the activity of
      a PPAR-dependent promoter in the absence of cotransfected PPARgamma. 15d-PGJ2 did
      not block nuclear translocation or DNA-binding activity of the transcription
      factor NFkappaB, but it did inhibit the activity of an NFkappaB reporter
      construct, suggesting that the mechanism of suppression of microglial iNOS by 15d
      PGJ2 may involve interference with NFkappaB transcriptional activity in the
      nucleus. Thus, our data suggest the existence of a novel pathway mediated by
      cyclopentenone prostaglandins, which may represent part of a feedback mechanism
      leading to the cessation of inflammatory glial responses in the brain.

PMID- 10200321
TI  - Seasonal neuroplasticity in the songbird telencephalon: a role for melatonin.
AB  - Neuroplasticity in the vocal control system of songbirds is strongly influenced
      by seasonal fluctuations in circulating testosterone. These seasonally plastic
      telencephalic structures are implicated in the learning and production of song in
      songbirds. The role of the indoleamine melatonin in seasonal adaptations in birds
      has remained unclear. In this experiment, European starlings were castrated to
      remove the neuromodulating activity of gonadal steroids and were exposed to
      different photoperiods to induce reproductive states characteristic of different
      seasonal conditions. Long days increased the volume of the song-control nucleus
      high vocal center compared with its volume on short days. Exogenous melatonin
      attenuated the long-day-induced volumetric increase in high vocal center and also
      decreased the volume of another song-control nucleus, area X. This effect was
      observed regardless of reproductive state. To our knowledge, this is the first
      direct evidence of a role for melatonin in functional plasticity within the
      central nervous system of vertebrates.

PMID- 10200322
TI  - The neutral cysteine protease bleomycin hydrolase is essential for epidermal
      integrity and bleomycin resistance.
AB  - The papain superfamily member bleomycin hydrolase (Blmh) is a neutral cysteine
      protease with structural similarity to a 20S proteasome. Bleomycin (BLM), a
      clinically used glycopeptide anticancer agent, is deaminated in vitro by Blmh. We
      used gene targeting to generate mice that lack Blmh and demonstrated that Blmh is
      the sole enzyme required for BLM deamination. Although some Blmh null mice were
      viable and reproduced, only about 65% of the expected number survived the
      neonatal period, revealing an important role for Blmh in neonatal survival. Mice
      lacking Blmh exhibited variably penetrant tail dermatitis that resembled rodent
      ringtail. The histopathology of the tail dermatitis was similar to skin lesions
      in humans with pellagra, necrolytic migratory erythema, and acrodermatitis
      enteropathica. Compared with controls, Blmh null mice were more sensitive to
      acute BLM lethality and developed pulmonary fibrosis more readily following BLM
      treatment. Thus, we have established that Blmh is an essential protectant against
      BLM-induced death and has an important role in neonatal survival and in
      maintaining epidermal integrity.

PMID- 10200323
TI  - Estrogen-induced activation of mitogen-activated protein kinase requires
      mobilization of intracellular calcium.
AB  - Estrogens and growth factors such as epidermal growth factor (EGF) act as
      mitogens promoting cellular proliferation in the breast and in the reproductive
      tract. Although it was considered originally that these agents manifested their
      mitogenic actions through separate pathways, there is a growing body of evidence
      suggesting that the EGF and estrogen-mediated signaling pathways are intertwined.
      Indeed, it has been demonstrated recently that 17beta-estradiol (E2) can induce a
      rapid activation of mitogen-activated protein kinase (MAPK) in mammalian cells,
      an event that is independent of both transcription and protein synthesis. In this
      study, we have used a pharmacological approach to dissect this novel pathway in
      MCF-7 breast cancer cells and have determined that in the presence of endogenous
      estrogen receptor, activation of MAPK by E2 is preceded by a rapid increase in
      cytosolic calcium. The involvement of intracellular calcium in this process was
      supported by the finding that the presence of EGTA and Ca2+-free medium did not
      affect the activation of MAPK by E2 and, additionally, that this response was
      blocked by the addition of the intracellular calcium chelator 1,2-bis(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetate. Cumulatively, these data indicate
      that the estrogen receptor, in addition to functioning as a transcription factor,
      is also involved, through a nongenomic mechanism, in the regulation of both
      intracellular calcium homeostasis and MAPK-signaling pathways. Although
      nongenomic actions of estrogens have been suggested by numerous studies in the
      past, the ability to link estradiol and the estrogen receptor to a well defined
      signaling pathway strongly supports a physiological role for this activity.

PMID- 10200324
TI  - Stable expression of human beta1,4-galactosyltransferase in plant cells modifies
      N-linked glycosylation patterns.
AB  - beta1,4-Galactosyltransferase (UDP galactose: beta-N-acetylglucosaminide: beta1,4
      galactosyltransferase; EC 2.4.1. 22) catalyzes the transfer of galactose from UDP
      Gal to N-acetylglucosamine in the penultimate stages of the terminal
      glycosylation of N-linked complex oligosaccharides in mammalian cells. Tobacco
      BY2 cells lack this Golgi enzyme. To determine to what extent the production of a
      mammalian glycosyltransferase can alter the glycosylation pathway of plant cells,
      tobacco BY2 suspension-cultured cells were stably transformed with the full
      length human galactosyltransferase gene placed under the control of the
      cauliflower mosaic virus 35S promoter. The expression was confirmed by assaying
      enzymatic activity as well as by Southern and Western blotting. The transformant
      with the highest level of enzymatic activity has glycans with galactose residues
      at the terminal nonreducing ends, indicating the successful modification of the
      plant cell N-glycosylation pathway. Analysis of the oligosaccharide structures
      shows that the galactosylated N-glycans account for 47.3% of the total sugar
      chains. In addition, the absence of the dominant xylosidated- and fucosylated
      type sugar chains confirms that the transformed cells can be used to produce
      glycoproteins without the highly immunogenic glycans typically found in plants.
      These results demonstrate the synthesis in plants of N-linked glycans with
      modified and defined sugar chain structures similar to mammalian glycoproteins.

PMID- 10200325
TI  - Molecular cloning and functional expression of gibberellin 2- oxidases,
      multifunctional enzymes involved in gibberellin deactivation.
AB  - A major catabolic pathway for the gibberellins (GAs) is initiated by 2beta
      hydroxylation, a reaction catalyzed by 2-oxoglutarate-dependent dioxygenases. To
      isolate a GA 2beta-hydroxylase cDNA clone we used functional screening of a cDNA
      library from developing cotyledons of runner bean (Phaseolus coccineus L.) with a
      highly sensitive tritium-release assay for enzyme activity. The encoded protein,
      obtained by heterologous expression in Escherichia coli, converted GA9 to GA51
      (2beta-hydroxyGA9) and GA51-catabolite, the latter produced from GA51 by further
      oxidation at C-2. The enzyme thus is multifunctional and is best described as a
      GA 2-oxidase. The recombinant enzyme also 2beta-hydroxylated other C19-GAs,
      although only GA9 and GA4 were converted to the corresponding catabolites. Three
      related cDNAs, corresponding to gene sequences present in Arabidopsis thaliana
      databases, also encoded functional GA 2-oxidases. Transcripts for two of the
      Arabidopsis genes were abundant in upper stems, flowers, and siliques, but the
      third transcript was not detected by Northern analysis. Transcript abundance for
      the two most highly expressed genes was lower in apices of the GA-deficient ga1-2
      mutant of Arabidopsis than in wild-type plants and increased after treatment of
      the mutant with GA3. This up-regulation of GA 2-oxidase gene expression by GA
      contrasts GA-induced down-regulation of genes encoding the biosynthetic enzymes
      GA 20-oxidase and GA 3beta-hydroxylase. These mechanisms would serve to maintain
      the concentrations of biologically active GAs in plant tissues.

PMID- 10200326
TI  - Ligand specificity of a high-affinity binding site for lipo-chitooligosaccharidic
      Nod factors in Medicago cell suspension cultures.
AB  - Rhizobial lipo-chitooligosaccharides (LCOs) are signaling molecules involved in
      host-range recognition for the establishment of the symbiosis with leguminous
      plants. The major LCO of Rhizobium meliloti, the symbiont of Medicago plants
      contains four or five N-acetylglucosamines, O-acetylated and N-acylated with a
      C16:2 fatty acid on the terminal nonreducing sugar and O-sulfated on the reducing
      sugar. In this paper, the ligand specificity of a high-affinity binding site (Nod
      factor binding site 2 or NFBS2), enriched in a plasma membrane-enriched fraction
      of Medicago cell suspension cultures, is reported. By using chemically
      synthesized LCOs, the role of structural elements, important for symbiotic
      activities, as recognition motifs for NFBS2 was determined. The results show that
      the substitutions on the nonreducing sugar of the LCOs (the O-acetate group, the
      fatty acid, and the hydroxyl group on the C4 of the sugar) are determinants for
      high-affinity binding to NFBS2. In contrast, the sulfate group, which is
      necessary for all biological activities on Medicago, is not discriminated by
      NFBS2. However, the reducing sugar of the LCO seems to interact with NFBS2,
      because ligand binding is affected by the reduction of the free anomeric carbon
      and depends on the number of N-acetyl glucosamine residues. These results suggest
      that the recognition of the LCOs by NFBS2 is mediated by structural elements in
      both the lipid and oligosaccharidic moities, but not by the sulfate group.

PMID- 10200327
TI  - Natural allelic variation at seed size loci in relation to other life history
      traits of Arabidopsis thaliana.
AB  - We have analyzed two Arabidopsis strains differing in the mean seed size and seed
      number they produced. The accession Cape Verde Islands (Cvi) yielded on average
      about 40% fewer seeds than the laboratory strain Landsberg erecta (Ler), but Cvi
      seeds were almost twice as heavy. Maternal and nonmaternal genetic factors were
      involved in the seed size variation, and interactions between both types of
      factors presumably occurred. The Ler/Cvi seed size difference increased through
      seed development from ovule maturation until seed desiccation, suggesting that
      multiple processes of seed development were affected. In addition, it involved
      changes in the final cell number and cell size of the seed coat and the embryo.
      Cell number variation was controlled mainly by maternal factors, whereas
      nonmaternal allelic variation mostly affected cell size. By using a recombinant
      inbred line population derived from Ler and Cvi, we mapped quantitative trait
      loci (QTLs) affecting 12 life history traits related to seed size, fruit size,
      seed number, and plant resources. Five of the seed size QTLs colocated with QTLs
      for other traits, suggesting that they control seed size via maternal components
      affecting ovule number and/or carpel development, ovule development, or
      reproductive resource allocation in the mother plant. The six remaining putative
      seed size QTLs did not show a significant effect on any other trait, suggesting
      that this allelic variation may be involved specifically in seed development
      processes.

PMID- 10200328
TI  - Genes for calcineurin B-like proteins in Arabidopsis are differentially regulated
      by stress signals.
AB  - An important effector of Ca2+ signaling in animals and yeast is the
      Ca2+/calmodulin-dependent protein phosphatase calcineurin. However, the
      biochemical identity of plant calcineurin remained elusive. Here we report the
      molecular characterization of AtCBL (Arabidopsis thaliana calcineurin B-like
      protein) from Arabidopsis. The protein is most similar to mammalian calcineurin
      B, the regulatory subunit of the phosphatase. AtCBL also shows significant
      similarity with another Ca2+-binding protein, the neuronal calcium sensor in
      animals. It contains typical EF-hand motifs with Ca2+-binding capability, as
      confirmed by in vitro Ca2+-binding assays, and it interacts in vivo with rat
      calcineurin A in the yeast two-hybrid system. Interaction of AtCBL1 and rat
      calcineurin A complemented the salt-sensitive phenotype in a yeast calcineurin B
      mutant. Cloning of cDNAs revealed that AtCBL proteins are encoded by a family of
      at least six genes in Arabidopsis. Genes for three isoforms were identified in
      this study. AtCBL1 mRNA was preferentially expressed in stems and roots and its
      mRNA levels strongly increased in response to specific stress signals such as
      drought, cold, and wounding. In contrast, AtCBL2 and AtCBL3 are constitutively
      expressed under all conditions investigated. Our data suggest that AtCBL1 may act
      as a regulatory subunit of a plant calcineurin-like activity mediating calcium
      signaling under certain stress conditions.

PMID- 10200330
TI  - Local instrumental variables and latent variable models for identifying and
      bounding treatment effects.
AB  - This paper examines the relationship between various treatment parameters within
      a latent variable model when the effects of treatment depend on the recipient's
      observed and unobserved characteristics. We show how this relationship can be
      used to identify the treatment parameters when they are identified and to bound
      the parameters when they are not identified.

PMID- 10200329
TI  - Psychophysical isolation of a motion-processing deficit in schizophrenics and
      their relatives and its association with impaired smooth pursuit.
AB  - Schizophrenia patients and many of their relatives show impaired smooth pursuit
      eye tracking. The brain mechanisms underlying this impairment are not yet known,
      but because reduced open-loop acceleration and closed-loop gain accompany it,
      compromised perceptual processing of motion signals is implicated. A previous
      study showed that motion discrimination is impaired in schizophrenia patients.
      Motion discrimination can make use of position and contrast as well as velocity
      cues. Here, we report that the motion discrimination deficit, which occurs in
      both schizophrenic patients and in their first-degree relatives, involves a
      failure of velocity detection, which appears when judging intermediate target
      velocities. At slower and faster velocities, judgments of velocity discrimination
      seemed normal until we experimentally disentangled velocity cues from nonmotion
      cues. We further report that compromised velocity discrimination is associated
      with sluggish initiation of smooth pursuit. These findings point to specific
      central nervous system correlates of schizophrenic pathophysiology.

PMID- 10200331
TI  - A study of 9-nitrocamptothecin (RFS-2000) in patients with advanced pancreatic
      cancer.
AB  - This ongoing study evaluates the efficacy of oral 9-nitrocamptothecin (9NC), or
      RFS-2000, in the treatment of advanced pancreatic cancer. Patients received 9NC
      orally for 5 days/week; 8 weeks of therapy is required to achieve minimum
      effective dose. Starting dose was 1.5 mg/m2/day, with adjustments made as
      necessary. Patients were analyzed for changes in tumor size by CT scan, changes
      in serum CA 19-9 tumor marker levels, quality of life, and survival. 107
      consecutive patients with advanced adenocarcinoma of the pancreas were enrolled
      before November 3, 1997. Of this group, 47 patients did not receive the minimum 2
      courses of treatment necessary to induce response, leaving 60 evaluable patients.
      Primary dose-limiting toxicities were myelosuppression and interstitial cystitis.
      No deaths were attributed to 9NC. Median survival was 6.5 months for the 107
      total patients and 8.7 months for the 60 evaluable patients, with one patient
      surviving at 44+ months. Of the 60 evaluable patients, 31.7% were responders
      (median survival 18.6 months; range 6.5-44.7+ months), 31.7% were stable (median
      survival 9.7 months), and 36.6% were non-responders (median survival 6.8 months).
      Fifty-seven previously untreated patients had a median survival of 7.3 months
      compared to 4.7 months for the 50 previously treated patients. Thirty-three
      patients who failed gemcitabine therapy prior to 9NC treatment had a median
      survival of 4.7 months. 9NC is safe and efficacious as first-line therapy for the
      treatment of advanced pancreatic cancer. It also shows some modest success as
      second-line therapy in treating gemcitabine failures.

PMID- 10200332
TI  - Fumonisin B1 induces apoptosis in cultured human keratinocytes through
      sphinganine accumulation and ceramide depletion.
AB  - Fumonisin B1 stimulates apoptosis in a variety of cell types and tissues. We
      examined the role of sphingolipid changes in fumonisin B1-stimulated apoptosis.
      Sphinganine accumulated rapidly, sphingosine levels remained unchanged, and
      ceramides decreased during fumonisin B1 exposure. Increased DNA fragmentation,
      decreased viability, and apoptotic morphology were observed in cells exposed to
      fumonisin B1, sphinganine, or N-acetylsphingosine. Co-exposure to N
      acetylsphingosine or beta-chloroalanine, which blocks sphinganine accumulation,
      partially protected cells from fumonisin B1-induced apoptosis. These results
      illustrate three sphingolipid-dependent mechanisms for inducing apoptosis:
      accumulation of excess ceramide, accumulation of excess sphinganine, and
      depletion of ceramide or complex sphingolipids derived from ceramide.

PMID- 10200333
TI  - Vaccinia virus-mediated expression of wild-type p53 suppresses glioma cell growth
      and induces apoptosis.
AB  - The use of vaccinia virus vectors for cancer gene therapy may become a powerful
      method to achieve efficient anti-tumor effects. We used recombinant vaccinia
      virus expressing wild-type p53 (rVV-p53) to examine the biological effects of
      exogenous tumor suppressor p53 in human (U-373MG, U-87MG, LN-Z308) and rat glioma
      cells (9L, C6) in vitro. All glioma cell lines infected with rVV-p53 exhibited
      growth inhibition and underwent apoptosis as demonstrated by morphological
      studies using nuclear staining and flow cytometry. The key role of p53 in cell
      growth inhibition was confirmed as measured by colony forming efficiency. Growth
      inhibition and apoptosis were independent of the endogenous p53 status of the
      glioma cell lines.

PMID- 10200334
TI  - CD44 expression in human meningiomas: An immunocytochemical, immunohistochemical
      and flow cytometric analysis.
AB  - CD44 is a polymorphic family of cell adhesion molecules that has been implicated
      in tumour invasion and metastasis. In this comparative analysis study, we
      investigated the expression of the standard form of CD44 (CD44s or CD44H) in 25
      early passage cultures of meningiomas and histological sections, using
      immunohistochemical, immunocytochemical and flow cytometry techniques. There were
      20 grade I, 3 grade II and 2 grade III meningiomas in the study which also
      included 2 recurrent meningiomas and 1 meningioma arising some time after
      previous radiotherapy. Immunocytochemistry and flow cytometry results on early
      passage culture cells show that although the majority of the meningiomas were
      strongly positive for CD44H, some were only weakly positive. Immunohistochemical
      studies revealed a great variability in staining patterns both within individual
      tumours and between different tumours. Generally, the intensity varied between
      strong and negative, and in most tumours that were immunopositive, there was a
      multifocal pattern of staining. Five meningiomas did not stain at all for CD44H.
      Taken together, these findings suggest that generally the flow cytometry results
      correspond well with those of both immunocytochemical and immunohistochemical
      techniques, with a few exceptions. It is concluded that microenvironmental
      factors may be responsible for the differential expression seen with different
      techniques.

PMID- 10200335
TI  - GSH, GSH-related enzymes and GS-X pump in relation to sensitivity of human tumor
      cell lines to chlorambucil and adriamycin.
AB  - Glutathione (GSH) contents and activities of glutathione S-transferase (GST),
      glutathione reductase (GSH-RD), glutathione peroxidase (GSHpx) and glutathione
      conjugate export pump (GS-X pump) were determined in eight human tumor cell lines
      with different sensitivities to adriamycin and chlorambucil. Correlations between
      sensitivities of the human tumor cells to adriamycin and chlorambucil and the
      glutathione related factors were analyzed statistically. Sensitivities of the
      human tumor cells to chlorambucil were found to be correlated to all the
      glutathione related factors tested (r=0.68-0.88). IC50 values of adriamycin were
      also positively correlated to GSH contents and activities of GSH-RD, GSHpx and GS
      X pump with r values ranging from 0.66 to 0.77 but not to GST activity (r=0.25).
      Chang liver cells with highest GSH content and highest activities of GST, GSH-RD,
      GSHpx and GS-X pump were most resistant to both adriamycin and chlorambucil.
      These data suggested that glutathione related factors may work as an overall
      detoxification system participating in the detoxification of anticancer drugs
      such as adriamycin and chlorambucil, and to be involved in cellular resistance to
      these drugs.

PMID- 10200337
TI  - Current applications and perspectives of diagnostic nuclear medicine in oncology.
      Task Group of Oncology.
AB  - The characteristic of nuclear medicine is that it gives images of organs,
      structures and physiological or pathological processes, detecting the
      distribution of several radio-pharmaceuticals according to their uptake and
      metabolism. Its imaging can provide morphological information while at the same
      time containing data on cellular activity and functions. Such molecular imaging
      fulfils the modern orientations of oncology, where there is a need to define the
      presence of a malignancy in the earliest and most effective way, to characterise
      the neoplasm in terms of biological characteristics (e. g., proliferation,
      aggressiveness, differentiation, receptor status) and to obtain fundamental
      issues in patient management such as evaluation of disease extent, monitoring of
      therapies and study of treatment-induced side effects. The aim of this position
      paper is to discuss the main indications of nuclear medicine in diagnostic
      oncology reporting the most recent developments in nuclear medicine, and an
      extensive list of the major indications for nuclear medicine procedures. The
      techniques have been labelled as when considered essential in the diagnostic
      process, when they can give useful additional or information in combination with
      other instrumental diagnostic approaches, and alternative when they may be
      performed instead of other tests. These indications were derived by a general
      consensus within the Task Group of Oncology of the World Federation of Nuclear
      Medicine and Biology, and it should be stressed that only the current role of
      nuclear medicine was considered. The Task Group does not claim to have covered
      the entire range of nuclear medicine indications; in fact it was agreed to
      include only the most widely used techniques. The highly specific or very
      exceptionally used applications, or those still in development or under
      evaluation in clinical trials were not taken into consideration. The conclusion
      is that the current relationship between nuclear medicine and oncology can be
      defined not only as satisfactory but also as extremely promising, as nuclear
      medicine has the potential to compete with the most advanced radiological
      techniques of imaging, perhaps not so much in terms of sensitivity but more so in
      terms of specificity and biological characterisation. Several novel diagnostic
      procedures are able to solve clinical problems for which traditional radiology
      has shown clear limitations. Nuclear medicine remains today a dynamic medical
      specialty because it includes a combination of advances in basic science
      research, technology, cell biology and medical practice and it cannot be excluded
      that the new lines of research both towards new radiopharmaceuticals and advanced
      instrumentation will offer in the future new stimulating opportunities.

PMID- 10200336
TI  - Anti-proliferating effects of ginsenoside Rh2 on MCF-7 human breast cancer cells.
AB  - Ginsenoside Rh2 (G-Rh2) isolated from the root of Panax ginseng has been shown to
      have anti-cancer proliferation, differentiation and chemopreventive effects in
      certain cancer cell types. We investigated the mechanism of G-Rh2-induced growth
      inhibition in MCF-7 human breast carcinoma cells. G-Rh2 significantly inhibited
      the cell growth in a concentration-dependent manner, which effect was reversible,
      and induced a G1 arrest in cell cycle progression. G-Rh2 treatment down-regulated
      the protein level of cyclin D3 but upregulated the expression of cyclin-dependent
      kinase (Cdk) inhibitor p21WAF1/CIP1. The increased levels of p21 were associated
      with increased binding of p21 and Cdk2 concomitant with marked decrease in Cdk2
      and cyclin E-dependent kinase activities with no changes in Cdk2 and cyclin E
      expression. G-Rh2 markedly reduced the phosphorylated retinoblastoma protein
      (pRb) and enchanced association of unphosphorylated pRb and the transcription
      factor E2F-1. These data suggest that G-Rh2 inhibited the growth of MCF-7 cells,
      by inducing protein expression of p21 and reducing the protein levels of cyclin D
      which resulted in the down-regulation of cyclin/Cdk complex kinase activity,
      decreasing phosphorylation of pRb, and inhibiting E2F release.

PMID- 10200338
TI  - Effect of doxorubicin on wild-type and deoxyadenosine-resistant mouse leukemia
      L1210 cells.
AB  - Wild-type (WT) mouse leukemia L1210 cells express steady-state levels of the mRNA
      and protein for p53. However, the p53 expressed by the wild-type cells is a
      mutant form of p53. A deoxyadenosine-resistant L1210 cell line (Y8) derived from
      the parental WT L1210 cells does not maintain constitutive levels of p53 mRNA or
      protein. Upon DNA damage, induced by doxorubicin, neither the WT nor the Y8 cells
      block in G0/G1; the cells block in G2/M. However, treatment of the Y8 cells with
      doxorubicin results in a much greater fraction of cells becoming apoptotic
      compared to the WT cells. Doxorubicin treatment resulted in the induction of p53
      mRNA in the WT cells, but not the Y8 cells. WAF1, c-myc and Bax mRNAs were also
      induced by doxorubicin in the WT cells but not in the Y8 cells. The constitutive
      levels of WAF1 and Gadd45, unexpectedly seen in the p53-deficient Y8 cells,
      decreased following doxorubicin treatment. The comparison of the effects of DNA
      damage, as measured by mRNA levels, induced by X-irradiation or doxorubicin were
      found to vary between the WT and Y8 cells and for the particular mRNA studied.
      The effect of doxorubicin or X-irradiation on the cell cycle could be overridden
      in the WT cells by caffeine. Comparisons of DNA damage induced by doxorubicin or
      X-irradiation show that although the Y8 cells are more sensitive to these
      damaging agents than the WT cells, the effects on gene expressions are not
      identical.

PMID- 10200339
TI  - Reduced substratum adhesion and decreased expressions of 1 and 4 integrins in
      human breast cancer cells with a property of anchorage-independent growth.
AB  - The proliferation of normal human breast epithelial (HBE) cells was found to be
      dependent on their attachment on a solid culture substratum, whereas human breast
      cancer MCF-7 cells could grow in soft agar. The attachment of the dissociated
      single HBE cells to the substratum was complete within 4 h after replating, and
      most of the cells once attached were detached from the substratum by incubation
      with trypsin for 30 min. In contrast, the attachment of MCF-7 cells to the
      substratum proceeded more rapidly compared to that of HBE cells, and more than
      90% of the MCF-7 cells once attached were detached within a 10-min incubation
      with trypsin. The attachment of HBE cells to the substratum was significantly
      inhibited by a function-blocking antibody to beta1 or beta4 integrin, whereas MCF
      7 cells were not prevented from attaching by the anti-integrin beta1 antibody as
      far as examined but were by the anti-integrin beta4 antibody at the highest
      concentration tested. The absolute amounts of beta1 integrin in HBE and MCF-7
      cells were comparable to each other, while the cell surface level of beta1 in the
      MCF-7 cells was only 10% of that in the HBE cells. Both the total and cell
      surface levels of beta4 integrin expression in the MCF-7 cells were 30-40% of
      those in the HBE cells. The results suggest that anchorage-dependent HBE cells
      attach to the culture substratum via both beta1 and beta4 integrins, thereby
      generating a strong adhesiveness to the substratum. In contrast, anchorage
      independent MCF-7 cells had reduced adhesiveness to the substratum, and this
      property is suggested to be due to decreased levels of cell surface beta1
      integrin and total beta4 integrin expressed compared to their levels in normal
      counterparts.

PMID- 10200340
TI  - Altered complex formation between p21waf, p27kip and their partner G1 cyclins
      determines the stimulatory or inhibitory transforming growth factor-beta1 growth
      response of human fibroblasts.
AB  - TGF-beta1 stimulates proliferation of WI38 human embryo fibroblasts but inhibits
      that of their SV40-transformed counterparts, VA13 cells. Protein expression
      levels of cyclins A, D1, E and that of cdk2 and cdk4 were not affected by TGF
      beta1 in either of these cells. However, TGF-beta1-treatment increases cdk2
      kinase activity in WI38 cells and reduces it in VA13 cells. The same treatment
      reduces the amount of p21waf present in complexes with cyclins D1 and E in growth
      stimulated WI38 cells, but the reverse applies in growth-inhibited VA13 cells.
      Mitogenic stimulation of WI38 fibroblasts correlated with decreased expression of
      p27kip protein and reduced amounts of it in complex with cyclin E. In contrast,
      proliferative inhibition of VA13 fibroblasts by TGF-beta1 caused a reduction of
      p27kip in complexes with cyclin D1, but increased it in complexes with cyclin E,
      without affecting the overall level of p27kip protein expression. Thus, in this
      human fibroblast model, TGF-beta1-mediated stimulation or inhibition of
      proliferation depends on modulation in the amounts of p21waf and p27kip in
      complexes with cyclins D1 and E.

PMID- 10200341
TI  - Expression of growth hormone receptor in human prostatic carcinoma and
      hyperplasia.
AB  - By reverse transcription-polymerase chain reaction the transcript of the growth
      hormone receptor (GHR) was proved in 21 human prostatic carcinomas and 19 benign
      prostatic hyperplasias. A new method for extracting RNA from paraffin-embedded
      tissue was established. Western immunoblotting using the monoclonal antibody mAb
      263 revealed that the growth hormone receptor protein is equally expressed in
      prostatic carcinoma and hyperplasia. As shown by immunohistochemistry, the GHR
      protein is synthesized in the epithelial cells of the tumor acini. On the
      contrary, GHR was not found in normal prostatic epithelium. Our results imply
      that the growth hormone receptor may facilitate prostatic tumor cell growth.

PMID- 10200342
TI  - CXCR4 mRNA expression in colon, esophageal and gastric cancers and hepatitis C
      infected liver.
AB  - We have recently demonstrated by Northern blot and RT-PCR that the mRNA
      expression of the alpha-chemokine hIRH/SDF-1alpha is reduced in hepatocellular
      carcinoma (HCC), several digestive tract cancers and premalignant colon adenomas,
      and that its receptor CXCR4 mRNA expression is reduced in HCC. Here we
      investigate the expression of CXCR4 mRNA expression in several digestive tract
      cancers and hepatitis C viral (HCV) infected liver, a premalignant condition.
      There was no difference in the CXCR4 mRNA expression in colon, esophageal or
      gastric cancers compared to non-cancerous tissues. This is significantly
      different from the reduced expression we have seen with hepatocellular carcinoma
      (p<0.05). To better refine regional tumor or hepatic cytokine mRNA analysis
      within a biopsy sample we describe a micro-isolation technique for RNA extraction
      from portal and triad areas of liver biopsies or other small malignant or non
      malignant biopsy samples suitable for use in RT-PCR and differential display
      reactions. In HCV liver biopsies, the expression of hIRH and its receptor CXCR4
      mRNA, corrected for G3PDH, was not significantly different from that of control
      non-HCV (steatosis) biopsies. CXCR4 is expressed on leukocytes and its expression
      was predicted to correlate with hepatic inflammation. CXCR4 receptor mRNA
      expression did correlate significantly with that of its ligand hIRH/SDF-1alpha
      (p=0.001), and with the severity of fibrosis (p<0.05), but not with portal
      inflammation (p<0.10), piecemeal necrosis (p<0.10), lobular inflammation
      (p>0.10), the presence of lymphoid aggregates (p>0.10), or the total histological
      activity index (p=0.07). There was no difference in expression of hIRH or CXCR4
      between responders and non-responders to interferon (IFN) treatment, while as a
      control, the responder group of patients did show a higher expression of IFNalpha
      receptor than the non-responder group (p=0.05).

PMID- 10200343
TI  - Reduced expression of the CXCR4 receptor mRNA in hepatocellular carcinoma and
      lack of inducibility of its ligand alpha-chemokine hIRH/SDF1alpha/PBSF in vitro.
AB  - Differential cDNA displays between hepatocellular carcinoma and adjacent non
      malignant tissues have previously detected a PCR product, hIRH (human intercrine
      reduced in hepatomas), equivalent to SDF1alpha/PBSF whose mRNA was lost from
      human hepatocellular carcinoma and other malignant and pre-malignant samples and
      malignant cell lines. There are no reports to date of the mRNA status of the
      receptor for hIRH/SDF1alpha/PBSF, CXCR4 in malignant tissues. We report here that
      there is a reduction in the mRNA expression of CXCR4 in hepatocellular carcinoma
      as estimated by Northern blot and RT-PCR and compared to the adjacent non
      malignant tissue. The average (mean SD) tumor/normal ratio for CXCR4 mRNA
      expression, determined by RT-PCR, was 0.65 0.36 in 10 pairs of hepatocellular
      carcinomas. There was no consistent loss of CXCR4 mRNA expression in a range of
      malignant cell lines. The 3'-non-coding region of hIRH, had typical early
      response gene element sequences. Despite the presence of these 3'-elements there
      was no induction of hIRH gene expression in human lung carcinoma A549 cells by
      tumor necrosis factor alpha, interleukin-2, lipopolysaccharide or phorbol
      myristic acetate, nor in human melanoma cell line SB-2 by uv irradiation, under
      conditions which induced the homologue CXC intercrine IL-8 expression.
      Furthermore, there was no induction of hIRH gene expression, but rather a
      suppression, upon serum or cytokine addition to serum-deprived fibroblast cell
      lines, to an in vitro mouse bone marrow preparation, and to monocytic cell line
      THP-1.

PMID- 10200344
TI  - Detection of DNA polymorphisms and point mutations of high-affinity nerve growth
      factor receptor (TrkA) in human neuroblastoma.
AB  - We have studied nerve growth factor (NGF) receptors in 63 neuroblastoma tissues.
      We found DNA polymorphisms of TrkA consisting in C-->T transitions in tyrosine
      kinase domain at 6773, 7232 and 7301 nucleotides. Both C/T alleles were detected
      in tumors belonging to patients at stages 1, 2, 3 and 4 but not in 4S that
      expresses only the allele with C-->T. Furthermore, we detected a GT transversion
      resulting in a Gly-->Val substitution in a stage 4 and a stage 4S samples. We
      report the first evidence of TrkA polymorphism and point mutations in
      neuroblastoma.

PMID- 10200345
TI  - Prevention of colonic preneoplastic lesions by the probiotic Lactobacillus
      acidophilus NCFMTM in F344 rats.
AB  - The experiments described here were aimed at developing novel probiotic strains
      that may aid in the reduction of colon cancer risk. We assessed the potential
      anticancer properties of Lactobacillus acidophilus NCFMTM in male F344 rats using
      inhibition of the formation of azoxymethane (AOM)-induced aberrant crypt foci
      (ACF) in the colon as the measure of preventive efficacy. At 6 weeks of age,
      groups of rats were fed the experimental diets containing 0, 2% or 4% lyophilized
      cultures of L. acidophilus NCFMTM. At 7 weeks of age, all animals in each dietary
      group, except the vehicle-treated rats, were s.c. injected with AOM (15 mg/kg
      body weight) once weekly for two weeks. The vehicle-treated groups were given
      s.c. injections of normal saline. All rats were necropsied 10 weeks after the
      last AOM injection and ACF in formalin-fixed, methylene blue-stained colonic
      tissues were counted under the light microscope. The contents of the cecum were
      analyzed for bacterial beta-glucuronidase activity. Diet supplementation with the
      probiotic strain NCFMTM significantly suppressed AOM-induction of colonic ACF, in
      terms of total number, as well as crypt multiplicity and number of ACF/cm2 colon
      (P<0.01 - 0.001). NCFMTM inhibited AOM-induced colonic ACF formation in a dose
      dependent manner (P<0.01). A significant dose-dependent reduction of cecal beta
      glucuronidase activities was observed in the rats fed 2% (P<0.04) and 4%
      (P<0.0001) NCFMTM. These results suggest that Lactobacillus acidophilus NCFMTM
      may potentially prevent colon cancer development. Further studies are warranted
      to determine the full potential of this probiotic strain in preclinical efficacy
      studies.

PMID- 10200346
TI  - Treatment of a de novo fludarabine resistant-CLL xenograft model with bryostatin
      1 followed by fludarabine.
AB  - WSU-CLL is a de novo fludarabine resistant cell line established from a patient
      with advanced chronic lymphocytic leukemia (CLL) refractory to chemotherapy
      including fludarabine (Flud). Our previous studies indicate that bryostatin 1
      (Bryo 1) induces differentiation of WSU-CLL and increases the ratio of dCK/5'-NT
      activity and Bax/Bcl-2. This study tests the hypothesis that Bryo 1
      differentiated cells are more susceptible to Flud than the parent WSU-CLL cells.
      Flud, given sequentially after Bryo 1, in vitro and in vivo animal studies
      resulted in significantly higher rates of growth inhibition and improved animal
      survival. Flud at 100 to 600 nM exhibited a dose-dependent growth inhibitory
      effect on the WSU-CLL cell line. The sequential exposure to Bryo 1 (10 nM for 72
      h) followed by Flud (100 nM) resulted in significantly higher rates of growth
      inhibition than either the reverse addition of these two agents or each agent
      alone, but was not significantly different than the concurrent addition of Bryo 1
      + Flud. Using 7-amino-actinomycin D staining and flow cytometry, apoptosis was
      seen in 40.8% of cells treated with Bryo 1 (10 nM, 72 h) followed by Flud,
      compared with Flud (100 nM, 72 h) followed by Bryo 1 (18.1%). To demonstrate that
      Bryo 1 enhancement of Flud efficacy was not restricted to in vitro culture, we
      used the WSU-CLL xenograft model in mice with severe combined immune deficiency
      (SCID). Bryo 1 + Flud at the maximum tolerated doses (75 microg/kg i.p. and 200
      mg/kg i.v., respectively) were administered to mice in different combinations.
      The survival in days, the tumor growth inhibition ratio (T/C), the tumor growth
      delay (T-C) in days, log10 kill, as well as mean tumor weight (mtw) of mice
      treated with Bryo 1 followed by Flud, were significantly better than control and
      other groups. T/C%, T-C, log10 kill and mtw were as follows: Bryo 1 (36.8%, 10
      days, 0.8, 375 mg); Flud (100%, 0. 0 day, 0.0, 1130 mg); Bryo 1 + Flud (14.3%, 12
      days, 0.95, 288 mg); Bryo 1 followed by Flud (4.6%, 17 days, 1.35, 35 mg); Flud
      followed by Bryo (40.3%, 10 days, 0.80, 175 mg). We conclude that: i) Bryo 1
      sensitizes WSU-CLL cells to Flud and enhances apoptosis; ii) the sequential
      treatment with Bryo 1 followed by Flud resulted in higher anti-tumor activity
      compared with either agent alone, in combination, or the reverse addition of
      these agents and iii) these results are comparable to those of Bryo 1 followed by
      2-CdA suggesting common pathway(s) of interaction between Bryo 1 and purine
      analogues.

PMID- 10200347
TI  - Isolation of protein kinase C-alpha-regulated cDNAs associated with breast tumor
      aggressiveness by differential mRNA display.
AB  - Elevated levels of protein kinase C (PKC) are associated with increased
      metastatic capacity in both human breast cancer cells and breast tumors. MCF-7
      breast cancer cells stably transfected with PKC-alpha were recently shown to
      display a more aggressive phenotype and increased tumorigenicity in nude mice. To
      identify genes involved in the progression to the aggressive phenotype, mRNA
      differential display was performed to isolate cDNAs that are differentially
      expressed between the parental, non-metastatic MCF-7 cell line and the metastatic
      derivative MCF-7-PKC-alpha cell line. One cDNA was identified which was
      upregulated and four cDNAs were downregulated in MCF-7-PKC-alpha cells. The
      upregulated cDNA may be a differentiation-specific gene as it is 100% homologous
      to a putative glialblastoma cell differentiation-related protein, GBDR1. DNA
      sequence analysis and flow cytometry revealed that three of the downregulated
      cDNAs correspond to histone 3.B, and integrins alpha3 and alpha6. The fourth
      downregulated cDNA clone, G2Q, is a novel sequence. G2Q is expressed in normal
      breast and bronchial tissue, but is downregulated in a variety of tumor cell
      lines and in aggressive primary and secondary breast tumors, suggesting that G2Q
      may be a useful prognostic indicator of tumor aggressiveness. Further,
      downregulation of G2Q expression in the non-metastatic MCF-7 cells by antisense
      oligonucleotides resulted in increased in vitro invasive capacity of these cells
      in a Matrigel matrice. This study provides the basis for identifying new genes
      involved in breast tumor progression and the role that PKC plays in the
      pathogenesis of this cancer.

PMID- 10200348
TI  - Induction of rat WT1 gene expression correlates with human chromosome 11p11.2-p12
      mediated suppression of tumorigenicity in rat liver epithelial tumor cell lines.
AB  - We have previously identified and mapped a locus within human chromosome 11p11.2
      p12 that suppresses the tumorigenic potential of some rat liver tumor cell lines.
      In the present study, possible molecular mechanisms of human 11p11.2-p12-mediated
      liver tumor suppression were investigated by examining gene expression patterns
      in suppressed and non-suppressed microcell hybrid (MCH) cell lines. The parental
      rat liver tumor cell lines (GN6TF and GP7TB) express moderate levels of p53 mRNA
      and protein, overexpress mRNAs for c-H-ras, c-myc, and TGFa, and do not express
      detectable levels of WT1 mRNA or protein. Suppression of tumorigenicity by human
      chromosome 11p11.2-p12 was not accompanied by significant alterations in the
      levels of expression of p53, c-myc, or TGFa. Expression of c-H-ras was decreased
      significantly in both suppressed and non-suppressed MCH cell lines, suggesting
      that down-regulation of c-H-ras is not directly responsible for tumor
      suppression. In contrast, the level of expression of WT1 correlated precisely
      with tumor suppression in this model system. All suppressed MCH cell lines
      expressed WT1 mRNA and protein at levels comparable to that of untransformed rat
      liver epithelial cells (WB-F344), whereas only trace WT1 mRNA and protein were
      detected in a non-suppressed MCH cell line. PCR analysis demonstrated that two
      suppressed MCH cell lines do not carry the human WT1 gene, indicating that WT1
      expression in these lines originates from the rat locus. Furthermore, RT-PCR
      analysis showed that each of the four known splice variants of the WT1 mRNA are
      expressed in these suppressed MCH cell lines, recapitulating the expression
      pattern observed in the untransformed rat liver epithelial cells. Re-expression
      of tumorigenicity by suppressed MCH cell lines was accompanied by the coordinate
      loss of human chromosome 11p11.2-p12 and of WT1 gene expression, suggesting that
      one or more human 11p11.2-p12 genes are required for sustained expression of WT1
      in these cell lines. Together, these results suggest that the molecular mechanism
      governing human chromosome 11p11.2-p12-mediated liver tumor suppression may
      involve induction of rat WT1 gene expression under the direct or indirect
      transcriptional regulation of a genetic locus (or loci) on human 11p11.2-p12.

PMID- 10200349
TI  - Proliferating cell nuclear antigen as a predictor of therapeutic effect of
      continuous 5-fluorouracil administration in gastric cancer.
AB  - The change of proliferating cell nuclear antigen (PCNA) expression was examined
      in three gastric cancer cell lines, MKN28, MKN45 and MKN74, during continuous or
      bolus exposure to 5-fluorouracil (5-FU). The cytotoxic effect of 5-FU was almost
      the same in all the cells. PCNA expression was higher at 24 and 72 h after
      continuous 5-FU treatment than before treatment. Continuous 5-FU treatment of
      cells revealed higher expression of PCNA protein and mRNA than did bolus
      treatment. Flow cytometry revealed that 5-FU increased cell population at the
      late G1 or S phase 24 and 72 h after treatment. PCNA values at the late G1 and S
      phase were significantly higher than those at other phases 24 h after treatment.
      These results suggest that PCNA expression increased due to cell cycle
      accumulation at late G1 and S phases. Thus PCNA values just after chemotherapy of
      gastric cancer may be useful in predicting the therapeutic effects of continuous
      5-FU administration.

PMID- 10200350
TI  - Systematic sequencing of the BRCA-1 coding region for germ-line mutation
      detection in 70 French high-risk families.
AB  - Seventy French high-risk families were screened for germ-line BRCA-1 mutations.
      The BRCA-1 coding region and the exon-intron boundaries were sequenced, except
      when pre-screening by PTT revealed a truncated protein in exon 11. Germ-line BRCA
      1 mutations were detected in 24% of families. The number of breast and ovarian
      cancers per family, a relative young age at ovarian cancer diagnosis, and the
      occurrence of breast and ovarian cancer in the same patient significantly
      predicted the presence of a BRCA-1 mutation. The low BRCA-1 mutation frequency
      suggested that some alterations were not detected and some families were probably
      BRCA-2 or BRCAx carriers.

PMID- 10200351
TI  - Novel 19-nor-hexafluoride vitamin D3 analog (Ro 25-6760) inhibits human colon
      cancer in vitro via apoptosis.
AB  - Our previously performed experiments clearly showed a significant VDR-mediated
      growth inhibitory effect of 1,25-dihydroxyvitamin D3 and its synthetic analogs in
      a variety of human cancer cells including human colon and breast cancer, soft
      tissue sarcoma, and malignant melanoma cell lines. The mechanisms by which 1, 25
      dihydroxyvitamin D3 and its synthetic analogs growth inhibit human cancer cells
      is poorly elucidated. The exposure of human colon cancer cells HT-29 to 1,25
      dihydroxyvitamin D3 or its analog, 1alpha, 25-dihydroxy-16-ene-23yne-26,27
      hexafluoro-19-nor-choleca lci ferol (Ro 25-6760), at the 10(-6) M concentration
      resulted in significant growth inhibition with induction of the apoptotic process
      after three days of treatment detected by TUNEL assay and agarose gel
      electrophoresis of DNA. As a logical link with DNA fragmentation analyses and
      TUNEL assay, cleavage of the 116 kDa PARP protein was accompanied by the
      appearance of a characteristic 85 kDa fragment of PARP in a population of
      floating cells after both treatments. The results of cell cycle analysis showed a
      G0/G1 phase block after three days of administration of either compound when
      compared with untreated cells. On day 4, G0/G1 cell cycle arrest remained on the
      same level in comparison with control. Paralleling the G0/G1 phase block, was a
      notable decrease in the number of cells in the S phase which also became
      significant after three days of treatment. The results of these experiments show
      that the newly developed 19-nor synthetic vitamin D3 analog, Ro 25-6760, as well
      as 1, 25-dihydroxyvitamin D3, induced the expression of p21waf1, resulted in a
      significant G1/G0 cell cycle arrest leading to impressive growth inhibition and
      induction of apoptosis associated with proteolytic cleavage of poly(ADP-ribose)
      polymerase (PARP) showing a possible involvement of apoptosis-specific activation
      of the ICE/CED-3 proteolitic pathway.

PMID- 10200352
TI  - Regression of DMBA-induced breast carcinoma following ovariectomy is associated
      with increased expression of genes encoding insulin-like growth factor binding
      proteins.
AB  - Insulin-like growth factor I (IGF-I) has well characterized mitogenic and
      antiapoptotic effects in both normal and neoplastic mammary epithelial cells
      which are mediated through the IGF-I receptor. IGF activity is modulated by a
      family of high affinity IGF binding proteins (IGFBPs 1-6). Here we show that gene
      expression of IGFBP-2, -3, -4 and -5 increases rapidly in DMBA-induced rat
      mammary tumors following ovariectomy. We observed a 90% reduction in volume of
      DMBA-induced rat mammary tumors by 14 days post-ovariectomy. The time course of
      maximal tumor regression was associated with increased gene expression of IGFBPs,
      as detected by Northern blot analysis. IGFBP-2, -3, -4 and -5 mRNA levels
      increased from 2- to 16-fold of control by 14 days of estrogen-ablation. These
      results are compatible with the hypothesis that response of DMBA-induced mammary
      tumors to estrogen deprivation therapies involves reduction of IGF bioactivity
      secondary to upregulation of expression of IGF binding proteins.

PMID- 10200353
TI  - Regulation of human head and neck squamous cell carcinoma growth in tissue
      culture by opioid growth factor.
AB  - Squamous cell carcinoma of the head and neck (SCCHN) is the sixth most common
      malignancy worldwide. Approximately half of the patients afflicted die within 5
      years of diagnosis, and surviving patients may be left with severe esthetic and
      functional compromise. In this study, we discovered that an endogenous opioid
      peptide, [Met5]-enkephalin, inhibited the growth of human SCCHN in vitro; in view
      of this pentapeptide's action it has been termed opioid growth factor (OGF). OGF
      was found to be a constitutively expressed, receptor-mediated growth inhibitory
      agent that appears to be autocrine produced and secreted. Growth regulation was
      dose-related, reversible, cytostatic, and independent of serum. All 6 human SCCHN
      cell lines examined exhibited growth modulation by OGF. Blockade of peptide
      receptor interaction by opioid antagonists (naltrexone), or addition of antibody
      to OGF, resulted in substantial increases in cell number compared to control
      levels, showing the tonic nature of OGF-zeta activity. Immunocytochemical studies
      detected both OGF and its related receptor, zeta, in these cells, correlating
      with earlier findings of peptide and receptor in specimens of SCCHN obtained at
      surgery. These data suggest that a native opioid peptide, OGF, interacts with a
      novel opioid receptor, zeta, to tonically arrest the growth of human SCCHN.

PMID- 10200355
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- 10200354
TI  - Combination paclitaxel and vinorelbine therapy: in vitro cytotoxic interactions
      and dose-escalation study in breast cancer patients previously exposed to
      anthracyclines.
AB  - The objectives of the present study were first to analyse the in vitro cytotoxic
      interactions between paclitaxel and vinorelbine in order to approach the optimal
      clinical scheduling in cancer patients, and second to determine the maximum
      tolerated doses of this combination without haematopoietic growth factor in
      breast cancer patients previously exposed to anthracyclines. The in vitro
      cytotoxicity of paclitaxel and vinorelbine alone, in combination and in sequence,
      was evaluated against the established human doxorubicin-resistant MCF7 (MCF7-R)
      breast carcinoma cell line using the standard isobologram methodology. Regarding
      the simultaneous exposure to vinorelbine and paclitaxel, the combined data points
      fell mainly on the left side of the envelope of additivity suggesting a
      synergistic interaction. Conversely the representative isobologram of MCF7-R
      cells for sequential exposure to vinorelbine followed by paclitaxel or paclitaxel
      followed by vinorelbine indicated antagonism. These results prompted us to
      perform a trial of paclitaxel/vinorelbine combination using the administration of
      these drugs on the same day directly one after the other. The dose-escalation
      trial included 20 women with metastatic breast cancer who were treated by
      paclitaxel every 3 weeks (135 mg/m2 starting dose) with 20 mg/m2 steps in
      subsequent cohorts of patients and vinorelbine (30 mg/m2 fixed dose). Patients
      were treated every 21 days. A total of 91 courses of therapy were administered to
      patients at three dose levels. Neutropenic fever was the dose-limiting toxicity
      at level 3 (paclitaxel 175 mg/m2). Other significant toxicities included sensory
      neuropathy, myalgias and fatigue. We conclude that paclitaxel 155 mg/m2 and
      vinorelbine 30 mg/m2 administered directly one after the other on the same day,
      every 21 days, are the doses recommended for further study.

PMID- 10200356
TI  - [A comparative study of HLA-A locus in northern and southern Chinese by means 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- 10200357
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- 10200358
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- 10200359
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- 10200360
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- 10200361
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 patientsL(r) 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- 10200362
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- 10200363
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- 10200364
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(2/5, 40%) lacked the NAIP exon 5. CONCLUSION: The results suggest a
      possible correlation between NAIP gene deletion and the disease severity of SMA.

PMID- 10200365
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- 10200366
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- 10200367
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- 10200368
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
      alphaCS mutation, the alpha QS mutation and the alphaWestmead 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- 10200369
TI  - [Using the method of two-color fluorescence in situ hybridization to detect
      aneuploidy of human sperms]
AB  - OBJECTIVE: To develope 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- 10200370
TI  - The effect of variation in knee center location estimates on net knee joint
      moments.
AB  - To test the sensitivity of knee flexion-extension moment patterns to variation in
      estimates of the knee center location (KCL), inverse dynamics analysis was
      performed using three different KCLs for data collected from 18 healthy adult
      subjects who walked at five different speeds (25%, 50%, 75%, 100% and 125% of
      0.785 statures.s< ?? opnbop ?? ?-1). The KCL, which was determined using data
      from static subject calibration trials, was varied in software by plus or minus
      10 mm in the anteroposterior direction. The effect of this KCL variation on knee
      moments was similar across subjects and at all five walking speeds. The relative
      knee center variation effect, expressed as a percentage of the mean knee moment,
      was progressively greater at slower walking speeds, up to 123% of the first
      extensor peak at the slowest speed. The implication of these results is that,
      while KCL variation does not affect the general shape of the moment pattern at
      more natural walking speeds, it can change the sign of the moment-and thus the
      interpretation-when the moment magnitude is small (e.g. at the very slow speeds
      used by some patients). When knee moments are of magnitudes less than or equal to
      the KCL variation effect, one cannot confidently interpret them as representing
      either a net flexor or extensor knee control strategy. Copyright 1998 Elsevier
      Science B.V.

PMID- 10200371
TI  - The 3-dimensional kinematics of the walking gait cycle of children aged between
      10 and 24 months: cross sectional and repeated measures.
AB  - The purpose of this study was to examine the 3-dimensional kinematics of 'normal'
      walking gait in young children. A cross sectional study using nine children aged
      between 10 and 24 months, filmed whilst walking at natural speed, was undertaken
      using two gen-locked video cameras. The children were at different stages of
      walking development (from 0.5 to 10 months of independent walking (IW)). Repeated
      measures were taken from two of the children at 10 and 17 months of age and then
      at 18 and 24 months respectively. 3-dimensional video digitisation techniques
      utilising the DLT algorithm were used to obtain variables of the gait cycle. The
      position and movement of the arms were identified as potential motor development
      patterns. Ranges of movement and motion patterns observed in other variables are
      useful to determine 'normal' walking gait in such young children. The knees and
      hips were flexed throughout the gait cycle. Inter-limb asymmetries were observed
      for the knee angle pattern and for the stance and swing phase time. The mean
      stance phase time and double support time were 4 and 15% (respectively) greater
      than in adult's gait. The findings of this study are useful as a guide to
      research, teaching and clinical professions in this area of biomechanics.
      Copyright 1998 Elsevier Science B.V.

PMID- 10200372
TI  - Intra-stride belt-speed variation affects treadmill locomotion.
AB  - For overground and treadmill locomotion to be mechanically similar, it is
      required that the belt speed of the treadmill is constant and the same to that of
      overground locomotion. Variation of the belt speed during a stride causes
      exchange of energy between the subject and the treadmill. This might be the cause
      of different kinematic patterns between overground and treadmill locomotion,
      which have been reported in literature. The aim of this study was to investigate
      whether the intra-stride belt-speed is variable, and whether differences in
      kinematic patterns can be attributed to these variations. Nine subjects walked
      and ran overground and on two treadmills that were differently susceptible to
      subjects' braking and accelerating forces. It was found that the speed variations
      during treadmill locomotion affect the kinematic parameters significantly. The
      amount of intra-stride belt-speed variation was found to depend on the power of
      the treadmill and the mass of the subject. Copyright 1998 Elsevier Science B.V.

PMID- 10200373
TI  - From stride period to stride frequency.
AB  - The stride-cycle frequency of gait data is often estimated by taking the inverse
      of the average stride-cycle time (stride period) over several stride-cycles. We
      derive the density function of the stride-cycle frequency frequency (stride
      frequency) and describe some of its properties. We also show the conditions under
      which the inverse of the mean stride period is a 'good' estimate of the mean
      stride frequency. Copyright 1998 Elsevier Science B.V.

PMID- 10200374
TI  - Multivariate graphical presentation for gait rehabilitation study.
AB  - This paper describes a procedure to determine the progress of the gait
      rehabilitation in relation to a reference obtained from a normal population. This
      procedure includes three stages: (1) data standardization, to give time and space
      aspects comparable from one individual to another; (2) monovariate and
      multivariate distance computation, to assess the difference between a disabled
      patient at a given time in the rehabilitation and the reference computed from
      individuals with a 'normal' gait; and (3) distance evolution. Since several
      variables are taken into account at the same time, the star view is proposed,
      each ray corresponding to the average distance between a given function of the
      patient undergoing rehabilitation and the corresponding reference function. Thus,
      as the rehabilitation process progresses, the distances are reduced and the star
      ray decreases. As a case study, the procedure is applied to the rehabilitation of
      a patient with an anterior cruciate deficient knee. Copyright 1998 Elsevier
      Science B.V.

PMID- 10200375
TI  - Sudden turns and stops while walking: kinematic sources of age and gender
      differences.
AB  - Background: Significant age and gender differences were found among healthy young
      and older adult subjects in their abilities to quickly turn or stop in order to
      avoid obstacles that suddenly appear in the gait path (Cao C, Ashton-Miller JA,
      Schultz AB, Alexander NB. Abilities to turn suddenly: effects of age, gender and
      available response time. J Gerontol Med Sci 1997;52A:M88-M93; Cao C, Ashton
      Miller JA, Schultz AB, Alexander NB. Abilities to stop suddenly: effects of age,
      gender, gait phase, and available response time. Submitted for publication, 1997
      (also available as a chapter in Cao C. Biomechanics of forward momentum arrest
      when walking: age and gender differences. PhD Dissertation, University of
      Michigan, 1996). The present study quantified the extent to which age and gender
      differences in those subjects' response kinematics affected the total time they
      needed to suddenly arrest their forward momentum. Methods: Age- and gender-group
      means of four measures of forward movement of the anterior surface of the abdomen
      were obtained: the duration of the first post-cue response phase, from the visual
      cue that initiated the arrest response to reaching peak velocity (T1);
      acceleration (A1) during this phase; and decelerations (D2 and D3) during two
      subsequent post-cue response phases. A three-line-segment representation of this
      forward velocity history was constructed. This representation was used to predict
      the differences in response time needed (NRT) to suddenly arrest momentum that
      resulted from measured age and gender differences in each of the four response
      kinematics measures. Results: The largest contributor to the age group difference
      found in NRT was the increase in T1 among the older adults. Among the older
      males, the next largest contributor was their larger value of A1, and among the
      older females, their substantially smaller value of D2. Among the young adults in
      sudden turns, no single kinematic parameter seemed primarily responsible for the
      gender difference found in the NRT. Among the older adults, the gender difference
      in D2 was almost fully responsible for the gender difference in NRT, in both
      sudden stops and turns. Conclusions: Much of the older adults' need for longer
      response times than those of the young was attributable to the lengthened first
      phase of their responses. Older females, in addition, needed longer response
      times than young adults or older males because, during the second phase of their
      responses, their decelerations were substantially smaller. These age and gender
      differences may have arisen in part from known age and gender differences in
      abilities to develop lower extremity joint torque strengths rapidly. Copyright
      1998 Elsevier Science B.V.

PMID- 10200376
TI  - Voluntary and involuntary adaptation of gait in Parkinson's disease.
AB  - Voluntary and involuntary adaptation of gait in Parkinson's disease (PD) were
      studied in two separate experiments. In the first experiment, effects of changes
      in voluntary control were studied by asking PD patients and age-matched healthy
      subjects to adapt their walking pattern to visual cues resulting in spatial
      constraints, and auditory cues resulting in temporal constraints on stepping
      movements. In the second experiment, the adaptation to increases in speed during
      overground and treadmill walking was studied. Most patients were able to adapt
      their walking patterns in accordance with instructions. Notwithstanding
      consistent differences in step length, the adaptation to different conditions
      under study was highly similar in PD patients and healthy subjects. Only during
      walking with visually guided step length were the observed adaptations in PD
      patients less consistent. Contrary to these dissimilarities, the involuntary
      adaptation of timing of support and swing phases within the stride cycle was very
      similar between groups. In all conditions, only with changes in step length could
      a change in relative timing be observed. Our findings show that voluntary
      adaptation of gait is possible in PD and that basic involuntary coordination
      mechanisms are preserved. The observed disturbances in stride length regulation
      probably reflect an inability to perform fast movements in PD. Copyright 1998
      Elsevier Science B.V.

PMID- 10200377
TI  - Analysis of adaptation in anteroposterior dynamics of human postural control.
AB  - To quantify the postural adjustments over time, twelve normal subjects were
      investigated with posturography during vibration either toward the calf or the
      paraspinal neck muscles; with eyes open vs. eyes closed. The stimulus response
      adjustments over time were found to be almost identical for all test conditions,
      though the responses were smaller during eyes open conditions. To determine the
      response adjustments and thus the dynamics of postural control, a system
      identification methodology incorporating both step response and dynamic feedback
      components was developed. This methodology can be used to quantify both short
      term stimulus response and postural adaptive adjustments when evaluating postural
      control performance. Copyright 1998 Elsevier Science B.V.

PMID- 10200378
TI  - The biomechanics of running.
AB  - This review article summarizes the current literature regarding the analysis of
      running gait. It is compared to walking and sprinting. The current state of
      knowledge is presented as it fits in the context of the history of analysis of
      movement. The characteristics of the gait cycle and its relationship to potential
      and kinetic energy interactions are reviewed. The timing of electromyographic
      activity is provided. Kinematic and kinetic data (including center of pressure
      measurements, raw force plate data, joint moments, and joint powers) and the
      impact of changes in velocity on these findings is presented. The status of
      shoewear literature, alterations in movement strategies, the role of biarticular
      muscles, and the springlike function of tendons are addressed. This type of
      information can provide insight into injury mechanisms and training strategies.
      Copyright 1998 Elsevier Science B.V.

PMID- 10200379
TI  - Time-domain analysis of foot-ground reaction forces in negotiating obstacles.
AB  - In recent years there has been increasing interest in the kinetic and kinematic
      characteristics of adaptations to obstacles and the contribution of these
      measures to understanding processes of gait control. This study investigated the
      lead and trail foot kinetic characteristics of unobstructed walking and stepping
      over obstacles for unimpaired, healthy adult males (n=6) and females (n=6). Two
      strain-gauged force platforms were employed during free-speed ambulation and
      stepping over obstacles adjusted to 10, 20 and 30% of leg length. In stepping
      over obstacles subjects increased obstacle-crossing step lengths and reduced
      obstacle-crossing speed as a function of obstacle height. The force-time data
      revealed that, compared with the lead foot, the trail foot generated greater
      vertical and anterior-posterior force during the push-off/propulsive phase across
      all obstacle conditions, had lower vertical peak force during mid-stance and
      produced greater vertical and anterior posterior impulses. While maximum
      propulsive force increased with obstacle height, its timing in the normalized
      step cycle was uninfluenced by height. Collectively, the results showed that the
      constraints of stepping over obstacles imposed different kinetic demands on the
      lead and trail foot; this is reflected in a complex interaction of braking and
      propulsive forces. Regulation of the step in this task was not mediated by a
      single parameter, such as vertical impulse. Copyright 1997 Elsevier Science B.V.

PMID- 10200380
TI  - Examination of trial-independent characteristics of body kinematics in response
      to similar postural perturbations.
AB  - This study investigated the variability of certain kinematic features describing
      body segmental movement in response to a series of consecutive, translational
      movements of the supporting base along the anterior-posterior direction of the
      subject. These kinematic features included the amplitude and timings of the
      angular displacement, velocity and acceleration of the head, trunk, thigh and
      shank. A group of 21 subjects was tested, with their ages ranging from 22 to 77
      years. The results showed that the amplitudes changed significantly from the
      first trial to the later trials in most of the variables observed. However, there
      existed certain features, other than the amplitude, that were invariant over
      consecutive trials. Specifically, the time at which the initial peak amplitude
      occurred, the onset time was found to be similar between trials. Copyright 1997
      Elsevier Science B.V.

PMID- 10200381
TI  - The modelling of adult spastic paretic stiff-legged gait swing period based on
      actual kinematic data.
AB  - With the ultimate goal to better demonstrate the biomechanics of spastic paretic
      stiff-legged gait, we simulated the motion of this gait disability, based on
      actual kinematic gait data. We created and applied a seven link-segment forward
      dynamic model to the gait kinematics of five adult subjects with this gait
      disability as a result of stroke. Trunk and limb segment torques developed during
      the affected limb's swing period of gait were calculated via inverse dynamic
      techniques from the measured kinematic data and incorporated into the forward
      dynamic model to simulate motion. In each case, the simulated motion corresponded
      to the directly measured kinematics. The hip and knee torques were then altered
      to predict potential resultant changes in knee flexion. Preliminary results
      suggest a stronger effect of hip torque than knee torque on knee angle, which
      also qualitatively corresponded with clinical data. This study demonstrates the
      feasibility of forward dynamic modelling based on actual clinical data and
      provides a further means to analyze potential mechanisms of this gait disability.
      Copyright 1997 Elsevier Science B.V.

PMID- 10200382
TI  - Retest reliability of spatiotemporal gait parameters in children and adults.
AB  - The objective of the study was to assess the retest-reliability of ten different
      gait parameters in healthy children (n=12; age 6-7 years) and adults (n=12; age
      21-35 years) during free-speed locomotion on a simple walkway. Further the intra
      subject variability of the stride dimensions was checked. On two occasions,
      spatial gait parameters were measured by footprint analysis, temporal dimensions
      were recorded using video-analysis. For spatial gait parameters, correlation
      coefficients (ICC, Pearson's r) between the test and the retest results were
      found to be high in adults and satisfying in children. The temporal parameters
      were less consistent. Generally the within-trial variability was higher in
      children than in adults. Conclusions: (i) The retest reliability for the
      measurement of the spatial gait parameters can be judged as high. (ii) For gait
      analysis in children it should be taken into account that gait parameters are
      more variable from trial to trial than in adults. Copyright 1997 Elsevier Science
      B.V.

PMID- 10200383
TI  - Neural control of locomotion; The central pattern generator from cats to humans.
AB  - In the last years it has become possible to regain some locomotor activity in
      patients suffering from an incomplete spinal cord injury (SCI) through intense
      training on a treadmill. The ideas behind this approach owe much to insights
      derived from animal studies. Many studies showed that cats with complete spinal
      cord transection can recover locomotor function. These observations were at the
      basis of the concept of the central pattern generator (CPG) located at spinal
      level. The evidence for such a spinal CPG in cats and primates (including man) is
      reviewed in part 1, with special emphasis on some very recent developments which
      support the view that there is a human spinal CPG for locomotion. Copyright 1997
      Elsevier Science B.V.

PMID- 10200384
TI  - Neuropathic diabetic patients do not have reduced variability of plantar loading
      during gait.
AB  - The objective of this study was to measure the variability of plantar loading
      during gait and explore the differences between neuropathic and non-neuropathic
      patients. At least 50 cycles of in-shoe plantar pressure data were recorded as 39
      patients (13 non-diabetic, 13 diabetic non-neuropathic, 13 diabetic neuropathic)
      walked overground in two different types of footwear. As measured by both log
      mean squared error and coefficient of variation, the results showed that
      variability was not significantly influenced by the diagnostic group for any shoe
      condition or for any region of the foot. These findings suggest that reduced
      variability in plantar loading is not a factor in the development of plantar
      lesions in neuropathic patients. Copyright 1998 Elsevier Science B.V. All rights
      reserved

PMID- 10200385
TI  - Differences in the gait characteristics of people with diabetes and
      transmetatarsal amputation compared with age-matched controls.
AB  - Although qualitative reports in the surgical literature suggest that people with
      diabetes mellitus (DM) and transmetatarsal amputation (TMA) walk well with
      regular shoes and a toe-filler, recent data indicates that this population has
      multiple complications and difficulty with functional mobility. A thorough
      description of their gait characteristics may provide insights to the cause of
      these difficulties. The purpose of this study was to compare selected gait
      characteristics of people with DM and TMA to age-matched controls. We studied 15
      subjects with DM and a TMA, and 15 age-matched controls with an overall mean age
      of 62.3+/-9.2 years. Data were collected with computer assisted video as subjects
      walked across a force platform. Range-of-motion (ROM), moments, and power were
      estimated at the ankle, knee, and hip in the sagittal plane using standard link
      segment methods. People with DM and TMA had decreased ROM excursion, peak
      moments, and peak power at the ankle. At the hip, people with DM and a TMA had
      decreased ROM excursion, an earlier onset of the hip flexor moment, but no
      differences in peak moments or peak power. Since people with DM and TMA have
      reduced ability to generate plantar flexor power at the ankle, they appear to
      rely more heavily on 'pulling' their leg forward from the hip using their hip
      flexor muscles. This compensation is not complete, however, as people with DM and
      a TMA take shorter steps and walk slower than controls. Additional research is
      needed to determine methods to improve or better compensate for these gait
      deviations during late stance phase. Copyright 1998 Elsevier Science B.V. All
      rights reserved

PMID- 10200386
TI  - Age differences in abilities to perform tandem stand and walk tasks of graded
      difficulty.
AB  - We quantified the abilities of 12 young (mean age 23.3 years) and 12 old (mean
      age 72.0 years) healthy women to tandem stand and tandem walk on a set of six
      beams, ranging from 15 cm down to 2.5 cm in width. Tandem stand tasks were
      conducted with eyes both open and closed. Tandem walk tasks were conducted with
      eyes open, and with both heel-to-toe and comfortable-distance step types.
      Significant age differences were found in the mean rate of successful performance
      for both tandem stand and tandem walk (P<0.001, rm-ANOVA). For both age groups,
      significant main effects for beam width were found for both tandem stand and
      tandem walk tasks. During tandem stand with eyes closed, young women were always
      successful on the widest beam while elderly women had an average success rate of
      only 62% and demonstrated an increased dependence on vision on narrower beams.
      Copyright 1998 Elsevier Science B.V. All rights reserved

PMID- 10200387
TI  - Does a single control mechanism exist for both forward and backward walking?
AB  - It has been proposed that the highly reproducible forward walking (FW) locomotor
      pattern is generated by a central neuronal program or central pattern generator
      (CPG) which provides the underlying mechanism which produces the coordinated
      walking movement. The purpose of this study was to quantify the differences in
      the muscular activation patterns during FW and backward walking (BW) at a
      constant step frequency and to determine if common features exist across both
      locomotor conditions. The hypothesis was that FW and BW are both mediated by the
      same CPG; therefore, only small modifications in the CPG are required in order to
      produce the different characteristics of each walking mode. The results noted
      kinematically reversed patterns at the hip and ankle joints between FW and BW.
      The knee joint movement pattern was similar between conditions, however, a phase
      shift of 14.3% of the gait cycle occurred. An approximately 25% phase shift in
      the muscle activation patterns existed between FW and BW in four of the six
      muscles studied. Additionally, a pattern recognition technique was applied to the
      combined EMG signals to determine the minimum number of features required to
      generate the measured muscular output. Only two main features were necessary to
      produce the EMG patterns for both the FW and BW condition. The main features in
      FW were more consistent than noted in BW. The results support the notion that a
      single spinal mechanism such as a CPG with two main features appears to be in
      control during both FW and BW. Copyright 1998 Elsevier Science B.V. All rights
      reserved

PMID- 10200388
TI  - Reproducibility of the walking patterns of normal young adults: test-retest
      reliability of the walk ratio(step-length/step-rate).
AB  - The walk ratio, step-length divided by step-rate, is a speed-independent index of
      walking patterns. This study reports on the reproducibility of the walk ratio in
      repeated tests. A total of 25 healthy young subjects walked on a flat floor at
      five different speeds and the test was repeated on the same day and after 3
      months. The walk ratio did not vary in the tests. Intraclass correlation
      coefficients of the walk ratio between the tests were 0.6-0.8 except for walking
      at extreme speeds. These results suggest that the walk ratio is a reliable
      measure for evaluating pathological and aging walking patterns. Copyright 1998
      Elsevier Science B.V. All rights reserved

PMID- 10200389
TI  - Postural responses to vibration of neck muscles in patients with uni- and
      bilateral vestibular loss.
AB  - Postural responses to vibration applied unilaterally to the dorsal neck muscles
      were recorded with a sway platform in 11 patients with bilateral vestibular loss
      (BLD), 13 patients with unilateral vestibular lesions (ULD) and 19 normal
      subjects. In the normals, the vibration induced a forward postural deviation.
      Vibration failed to induce postural sway in the BLD patients but induced a
      backwards head movement in 7 patients. In the ULD patients, vibration
      contralateral to the lesion induced normal forward sway, whereas ipsilateral
      vibration resulted in sway directed to the side of the lesion and backwards. The
      findings demonstrate the importance of concurrent vestibular signals in
      determining the behavioural response to neck afferent input. We propose that in
      normal subjects the intact vestibular signal gives no confirmation that a head
      movement has occurred so it is assumed that the lower body has tilted forwards
      which provokes a compensatory sway. In the total absence of vestibular function
      the neck signal may represent a real head movement so the preferential response
      is a head tilt to restore upright posture. The vestibular imbalance in the ULD
      patients is roughly equivalent to the asymmetrical signals obtained in a normal
      subject during head rotation to the intact side. The stretch signal induced by
      ipsi-lesional vibration confirms possible head rotation, thus provoking a
      compensatory postural sway. Copyright 1998 Elsevier Science B.V. All rights
      reserved

PMID- 10200390
TI  - The influence of segment endpoint kinematics on segmental power calculations.
AB  - Segment power can be estimated from the rate of change of segment energy or from
      segment endpoint dynamics. The inequality between these two calculations is
      termed the segment power imbalance (DeltaP). Explanations for this imbalance have
      been largely anecdotal. We used 3D gait data for 20 young, healthy adults to show
      experimentally that DeltaP is always zero when rigid body assumptions are
      strictly adhered to. We show mathematically and experimentally that DeltaP is non
      zero (range: <1-100 W) when segment endpoints move relative to the segment center
      of mass (COM). We also show that Lagrangian numerical differentiation of segment
      endpoint trajectories produce small velocity artifacts which result in observable
      DeltaP (range: 0.3-5 W). The benefits of obtaining a small DeltaP was found to be
      offset by large discrepancies (range: 8-54 W) in joint power across the joint
      gap. For the foot, large DeltaP (range: 23-106 W) was observed when the distal
      velocity component included velocity of the center of pressure relative to the
      foot's COM. Our results suggest that, unless interpreted carefully, segment power
      calculations can potentially lead to erroneous clinical judgement. Copyright 1997
      Elsevier Science B.V.

PMID- 10200392
TI  - Neural control of locomotion: sensory control of the central pattern generator
      and its relation to treadmill training.
AB  - Many studies have shown that a special treadmill training is effective in
      restoring locomotor function in cats with a complete spinal lesion. In the last
      few years it has become possible to regain some locomotor activity in patients
      suffering from a spinal cord injury through an intense training on a treadmill,
      as in cats. The ideas behind this approach owe much to insights derived from
      studies on spinalized animals. The neural system responsible for the locomotor
      restoration in both cats and humans is thought to be located at spinal level and
      is referred to as the central pattern generator. The evidence for such a spinal
      central pattern generator is reviewed in part 1. An important element in the
      treadmill training for both spinal injured cats and humans is the provision of
      adequate locomotor related sensory input, which can possibly activate and/or
      regulate the spinal locomotor circuitry. This part of the review deals with the
      afferent control of the central pattern generator. Furthermore, the results of
      treadmill training for both cats and humans and their relation to sensory input
      are treated. These insights can possibly contribute to the design of a better
      treadmill training program for the rehabilitation of gait in spinal cord injured
      patients. Copyright 1998 Elsevier Science B.V. All rights reserved

PMID- 10200391
TI  - Lateral pelvic displacement during walking: retest reliability of a new method of
      measurement.
AB  - This study examined the retest reliability of a new method of measuring the
      amplitude and symmetry of lateral pelvic displacement (LPD) during walking.
      Previous methods of quantifying LPD did not consider variations in walking
      direction or enable quantification of side-to-side symmetry of LPD. Therefore,
      the new method was developed to measure the amplitude and symmetry of LPD
      relative to the base of support provided by the feet. Three-dimensional motion
      analysis was used to collect the coordinates of markers placed on the sacrum and
      heels of 20 unimpaired adults. Subjects performed three 10 m walking trials at
      their preferred speed. Between trial 1 and 2 the markers were removed and then
      reattached. Between trial 2 and 3 the markers remained attached. Retest
      reliability was high for consecutive measurements of amplitude of LPD (ICC
      (2,1)=0.91), and marker reattachment did not affect the degree of reliability
      (ICC (2,1)=0.94). The reliability was also high for consecutive measurements of
      symmetry of LPD (ICC (2,1)=0.80). Marker reattachment did however reduce the
      reliability of symmetry measures (ICC (2,1)=0.54). This study provides data on
      the retest reliability of a new method of measuring LPD in unimpaired subjects
      against which the performance of patients can be compared. Copyright 1998
      Elsevier Science B.V. All rights reserved

PMID- 10200394
TI  - The initiation of gait in young, elderly, and Parkinson's disease subjects.
AB  - Gait initiation is a transient movement between upright posture and steady-state
      gait. Kinematic, kinetic and electromyographic data have been documented in
      healthy young subjects. However, there is little published data on the elderly
      and on Parkinson's disease (PD) subjects who are known to 'freeze' when
      initiating gait. It was the purpose of this project to measure gait initiation in
      young, healthy elderly and PD subjects. The results showed many differences
      between the young and elderly and the elderly and PD subjects. However, if all
      dependent variables were normalized to gait velocity there were no differences at
      the P<0.05 level. The results showed a progressive slowing from the young to the
      elderly to the PD subjects. There does not appear to be a relationship between
      the PD subject's steady-state velocity and their age, number of years diagnosed,
      number of hours off medication, or the rating on the Hoehn and Yahr scale.
      Copyright 1998 Elsevier Science B.V.

PMID- 10200393
TI  - Knee kinetics in trans-tibial amputee gait.
AB  - This study evaluated the mechanics of the knee during gait in persons with trans
      tibial amputations. Spatiotemporal, kinematic, kinetic, and electromyographic
      data (EMG) were collected from ten individuals with trans-tibial amputations and
      ten control subjects during level walking. Results found that the trans-tibial
      amputee (TTA) group had significantly greater EMG activity of the knee extensors
      and knee flexors compared to normal. The muscle action of the TTA group was
      inconsistent with the knee kinetic data as demonstrated by a minimal external
      knee flexion moment and negligible knee power. The discrepancy between the
      mechanical and physiological measures of knee demand in this population
      illustrates the need for an integrated approach for the study of joint function
      during gait (i.e. EMG in combination with kinetic measures). Copyright 1998
      Elsevier Science B.V.

PMID- 10200395
TI  - A new gait parameterization technique by means of cyclogram moments: Application
      to human slope walking.
AB  - A new parameterization technique for the systematic characterization of human
      walking gait in diverse external conditions is proposed in this work. By
      parameterization we mean a quantitative expression of certain gait descriptors as
      the function of an external parameter, such as the ground slope. The mathematical
      quantifies derived from the geometric features of the hip-knee cyclograms are the
      main gait descriptors considered in this study. We demonstrate that these
      descriptors, expressed in a general setting as the geometric moments of the
      cyclogram contours, can meaningfully reflect the evolution of the gait kinematics
      on different slopes. We provide a new interpretation of the cyclogram perimeter
      and discover two potential invariants of slope-walking gait. Experimental slope
      walking data obtained for each 1 degrees interval within the range of -13 to +13
      degrees (+/-23.1%) on a variable-inclination treadmill was used in this study.
      The parameterization procedure presented here is fairly general in nature and may
      be employed without restriction to any closed curve such as the phase diagram,
      the moment-angle diagram, and the velocity-velocity curves of human gait. The
      technique may be utilized for the quantitative characterization of normal gait,
      global comparison of two different gaits, clinical identification of pathological
      conditions and for the tracking of progress of patients under rehabilitation
      program. Copyright 1998 Elsevier Science B.V.

PMID- 10200396
TI  - Measuring changes in step parameters during an exhausting running exercise.
AB  - A treadmill with four force transducers was used to analyze gait during running.
      39 volunteers ran on a treadmill until they were exhausted. The step parameter
      variances showed a very distinct change in time. 17 subjects showed a sudden
      increase in variance. The other 22 subjects did not show such an effect, probably
      because they stopped too soon. This was confirmed by lactate measurements. In
      conclusion, the described treadmill is able to register continuously the running
      pattern of healthy volunteers. During an exhausting exercise, the running pattern
      becomes irregular in the last phase of the exercise. Copyright 1998 Elsevier
      Science B.V.

PMID- 10200397
TI  - Selective dorsal rhizotomy as a treatment option for children with spastic
      cerebral palsy.
AB  - Cerebral palsy is the most common motor disorder originating in childhood and
      spasticity is the most frequent manifestation. The treatment strategies to reduce
      spasticity and thereby ameliorate the attendant gait abnormalities have included
      physiotherapy, orthoses, antispastic medications, orthopaedic surgery and
      neurosurgery. Of these, the neurosurgical procedure known as selective dorsal
      rhizotomy has gained widespread exposure, and indeed acceptance, over the past
      two decades, despite there being some controversy as to its efficacy. In this
      paper we review: cerebral palsy, including classification and treatment;
      selective dorsal rhizotomy, including historical background, patient selection,
      operative procedure, clinical outcome and complications; and gait analysis
      studies, including temporal-distance parameters, joint kinematics, normalisation
      for growth, and long-term follow-up. Both the short-term (1 year) and long-term
      (10 years) evidence has demonstrated that selective dorsal rhizotomy not only
      reduces spasticity but it also provides lasting functional benefits as measured
      by improved range of motion during gait. Rhizotomy is not a panacea for children
      with spastic diplegia but it is an important treatment option for the clinician
      to consider. Copyright 1998 Elsevier Science B.V.

PMID- 10200398
TI  - Can transverse plane rotations be estimated from video tape gait analysis?
AB  - The use of video tape in gait analysis is widespread and is frequently used when
      more sophisticated 3-dimensional analysis systems are not available or cannot be
      used. Its major shortcoming however is that it does not readily yield information
      about rotations in the transverse plane which may be amongst the most
      diagnostically significant features of pathological gait. This paper describes an
      inexpensive device which may be used, in conjunction with video taping, to aid
      visual estimation of transverse plane rotations, and quantifies the accuracy with
      which this was done by experienced observers. Copyright 1998 Elsevier Science
      B.V.

PMID- 10200399
TI  - Multifactorial estimation of hip and knee joint centres for clinical application
      of gait analysis.
AB  - Estimation of joint centres is required in gait analysis for kinematic and
      kinetic elaboration. In general, the method is based on regression equations and
      palpation of bone prominences. A kinematic approach can also be used at the hip
      joint but appears to be more demanding for the patients. The method presented
      here combines different independent approaches and is aimed at reducing the
      estimation errors caused by from skin motion artefacts and statistical variance
      of anthropometric data. It is based on minimising an optimisation function in
      which data from gait kinematics, anthropometric measurements and statistically
      derived morphological parameters are properly weighted. The procedure is suitable
      for clinical applications where the range of motion might be reduced and the
      patients can not perform complicated exercises. Validation has been made on ten
      normal subjects and ten patients with spina bifida. The results show that the
      reproducibility of the estimation and the congruency with the external
      measurements is improved with respect to both the morphologically based approach
      and the kinematic method. Copyright 1998 Elsevier Science B.V.

PMID- 10200400
TI  - Effects of age, available response time and gender on ability to stop suddenly
      when walking.
AB  - Background: Injuries may occur during walking when a sudden stop to avoid a gait
      path obstacle is called for unexpectedly, but cannot be completed in the time
      available. Little is known about abilities, particularly those of older adults,
      to stop suddenly. Methods: Twenty young (mean age 23.4 years) and 20 older (72.6
      years) healthy and physically active adults with equal numbers of females and
      males in each age group were studied. While walking straight ahead at
      approximately 1.3 m/s, they were cued by a light at one of five possible
      locations to stop as quickly as possible. Subjects were given available response
      times (ART), the times between the visual cue to stop and potential passage
      through a virtual wall that was outlined by the array of lights used to cue the
      subjects, ranging from 375 to 825 ms in 75-ms increments. The rate of success
      (RS) in completing the stops as prescribed was determined and the effects on RS
      of age, available response time and gender were examined. Regression analyses
      were used to interpolate the RS data. Results: At all ART, older female (OF)
      subjects had a significantly lower rate of success (RS) than either older male
      (OM) or young adult (YA) subjects. At an ART of 525 ms, for example, RS was 58%
      for YA and 51% for OM, but only 23% for OF. The regression analyses suggested
      that OM in the mean would have needed 10 ms longer and OF 70 ms longer than YA to
      achieve a 50% RS. No significant gender difference in RS were found among YA.
      Conclusions: The healthy and physically active older female subjects in this
      study needed longer available response times, and thus longer available stopping
      distances, than did the young adults or the older males to succeed as well in
      stopping suddenly while walking at their comfortable gait speed. Copyright 1998
      Elsevier Science B.V.

PMID- 10200401
TI  - Geometrical analysis of hip and knee joint mobility in cerebral palsied children.
AB  - The present investigation attempted to define a geometrical hexagon model for
      representing the sagittal range of motion (ROM) of hip and knee joint. The effect
      of both monoarticular and biarticular muscles on joint mobility in children with
      spastic cerebral palsy (SCP) were analyzed by this geometrical method.
      Photographic analysis was used to measure hip and knee joint angle at six
      different boundary positions. The ROM in normal children indicated age dependent
      reduction of maximal hip flexion and shortening of hamstring and rectus femoris
      muscles. A number of SCP children showed greater reduction of both hip flexion
      and extension and shortening of hamstring and rectus femoris muscles, whereas the
      ROM of knee joint was similar to that in normal children. The deteriorated hip
      joint mobility seems to be associated with shortening of muscle due to their
      intrinsic spasticity. The impaired ROM was more noticeable in SCP non-ambulator
      child than in independent ambulator. Thus, more extended range and frequent
      opportunity of joint motion may play an important role in improving the joint
      mobility in this patient group. Copyright 1998 Elsevier Science B.V.

PMID- 10200402
TI  - Center of gravity dynamic stability in normal and vestibulopathic gait.
AB  - The purpose of this study was to examine the three-dimensional whole body center
      of gravity (CG) kinematics during free and paced gait in healthy subjects (n=16)
      and individuals with vestibulopathy (n=8). The cycle time, double and single
      stance phase durations, values and timing of CG forward velocity, and CG vertical
      displacement were recorded using an 11 segment, 66 degree of freedom whole body
      model. The free speed gait of the vestibulopathic individuals was remarkable for
      increased cycle time, increased percentage of time spent in the double stance
      phase, decreased forward velocity of the CG, and decreased vertical displacement
      of the CG. However, during paced gait, no statistically significant differences
      were found between the vestibulopathic and control groups in all measures. In all
      groups, CG horizontal velocity maxima and minima significantly lagged CG vertical
      minima and maxima respectively. We conclude that whole body CG control does not
      result purely from optimization of mechanical potential and kinetic energy
      exchanges: our temporal offsets in the maxima and minima of the CG horizontal
      velocity and vertical displacement make this mechanically impossible.
      Furthermore, individuals with vestibular impairment may self-select a slower
      walking speed to ease their biomechanic stability challenge despite being able to
      ambulate faster with 'normal' CG velocities and displacements. Copyright 1998
      Elsevier Science B.V.

PMID- 10200403
TI  - Axial synergies in parkinsonian patients during voluntary trunk bending.
AB  - During upper trunk movements, the axial kinematic synergies (opposite movements
      of upper and lower segments) preserve the balance by minimizing the antero
      posterior center of gravity (CG) shift due to the movement. Forward and backward
      upper trunk movements were analyzed in a population of parkinsonian patients (PD)
      that were subject to falling, in order to determine whether an impaired control
      of the kinematic synergies might explain the falling. Ten PD (stage III-IV of the
      Hoehn and Yahr classification; Hoehn MM, Yahr MD. Parkinsonism: onset,
      progression and mortality. Neurology 1967;17;427-432) were compared to seven age
      matched control subjects (CS). Kinematic analysis and force platform recordings
      were carried out. Principal Component (PC) analysis was performed to measure the
      coupling between hip, knee and ankle joint angles during the movement. (1) In
      both PD and CS, the first principal component (PC1) was found to account for 98%
      or more of the joint angles changes, which indicates that there exists a strong
      coupling between the angles during the movement; however, the part of the
      movement not accounted for by PC1 was twice as high in PD as in CS. (2) The
      intertrial variability between the angle ratios was about twice as high in PD as
      in CS. (3) The absolute value of the antero-posterior CG shift occurring during
      the movement significantly increased in PD in the case of backward movements,
      both fast and slow. (4) As a high correlation was found between actual CG shift
      and its estimation based on the observed interjoint coordination, the increased
      CG shift in PD was related to unproper set of ratios between joint angles. It was
      concluded that the control of the kinematic synergy is preserved on the whole in
      PD, with an increased variability and unproper set of the ratios between joint
      angular changes. This may lead to CG shifts to beyond the support surface,
      especially in backward bending. Copyright 1998 Elsevier Science B.V.

PMID- 10200404
TI  - Postural sway and balance testing: a comparison of normal and anterior cruciate
      ligament deficient knees.
AB  - The purpose of this study was to assess postural sway and balance in normal and
      anterior cruciate ligament (ACL) deficient (ACLD) knees. Performance was assessed
      in 15 ACLD and 15 matched control (CON) subjects whilst standing on a postural
      sway meter and on a balance board. On both pieces of apparatus subjects attempted
      to maintain balance for 30 s under six different conditions; (1) and (2) standing
      on both legs with eyes open and closed; (3) and (4) standing on the injured leg
      with eyes open and closed; and (5) and (6) standing on the non-injured leg with
      eyes open and closed. Performance on the postural sway meter and balance board
      deteriorated significantly when both ACLD and CON stood on one leg (P<0.01), and
      when eyes were closed (P<0.01). This was independent of whether the leg was
      injured or not. The interaction of vision loss and single leg stance resulted in
      a significant deterioration in balance board performance on the injured leg
      compared to the non-injured leg in the ACLD group. Results suggest that use of a
      postural sway meter for predicting function and stability during dynamic
      activities in ACLD subjects may be inappropriate. Copyright 1998 Elsevier Science
      B.V.

PMID- 10200405
TI  - Electromyography in the biomechanical analysis of human movement and its clinical
      application.
AB  - This article introduces the area of scientific study of human movement. It is
      primarily intended for readers who wish to form a judgement on the usefulness of
      scientific movement analysis techniques in the treatment process of patients with
      abnormal movement patterns. With a focus on the analysis of human locomotion, the
      paper outlines the historical development of a biomechanical approach towards the
      understanding of human movement patterns. This approach alone proves to be
      inadequate in supplying reliable information on neuromuscular control of
      movement. It follows that electromyographic techniques are essential for this
      purpose. Scientific literature reveals relevant practical usability of such
      information. This is the rationale for a review of the historical, physiological,
      technical and methodological background of electromyographic analysis of
      movement. The field of management and rehabilitation of motor disability is
      identified as one important application area. On the basis of relevant
      literature, the present paper asserts that scientific analysis of human movement
      patterns can materially affect patient treatment. It provides evidence that
      patient management and rehabilitation processes in central neurological disorders
      can be improved through electromyographic techniques. In particular, this
      evidence supports the use of electromyography for surgical planning in children
      with cerebral palsy. The paper concludes with a view on future directions in
      research, development and applications of scientific analysis of human movement.
      Copyright 1998 Elsevier Science B.V.

PMID- 10200406
TI  - Muscle activation characteristics of stance balance control in children with
      spastic cerebral palsy.
AB  - Two studies were conducted to investigate muscle recruitment of children with
      spastic cerebral palsy in response to unexpected perturbation of balance in
      stance. The aim of the studies was to investigate neural and non-neural
      mechanical contributions to muscle responses differences these children display
      when maintaining balance. In the first study, muscle responses of children with
      spastic diplegia were compared to typically developing children with similar
      levels of walking experience. Each child stood on a moveable platform that was
      displaced backward. Electromyographic recordings of posterior agonist and
      anterior antagonist muscles of the legs and trunk were analyzed and compared to
      those of normal children who had obtained a similar developmental levels of
      mobility. Children with spastic cerebral palsy were found to have an increase in
      antagonist recruitment and decreased trunk activation when compared to typically
      developing children at the same level of walking experience. Developmental trends
      were noted to be similar in all children with or without pathology. As children
      gained independent walking skills, they demonstrated shorter onset latencies in
      leg and thigh muscles. In the second study, older children with no pathology were
      perturbed in crouch stance, simulating the posture of their matched children with
      cerebral palsy. Changes in their muscle responses were observed to more clearly
      approximate the muscle onset latency organization of children with spastic
      diplegia. Results of these studies suggest that muscle recruitment differences
      for balance control in children with spasticity are due to CNS deficits as well
      as mechanical changes in posture. Copyright 1998 Elsevier Science B.V.

PMID- 10200407
TI  - Effect of muscle strength and movement speed on the biomechanics of rising from a
      chair in healthy elderly and young women.
AB  - The ability to rise from a chair is an important task of daily living that is
      difficult for many elderly individuals to perform, and is particularly
      challenging when performed quickly. It is important to understand what factors
      limit performance of the task in older people, so that effective remedial
      approaches can be developed. In this study, we quantified lower-extremity muscle
      strength and chair-rise biomechanics in 12 young and 26 healthy elderly women
      during chair rise at normal and fast speeds without use of the hands. We found
      that hip and knee extensor torques, vertical and horizontal momentum, and
      vertical and horizontal ground reaction forces increased in the same way with
      speed for all subjects. All subjects increased their speed from normal to fast
      trials, but the young subjects were able to rise more quickly in the fast trials.
      In the normal speed trials, elderly subjects generated more trunk flexion and
      horizontal momentum while still in contact with the chair. Muscle activity
      patterns were similar for all subjects except that the elderly activated the
      ankle extensors earlier than the young. Although the elderly subjects were much
      weaker relative to body weight than the young subjects (48.5+/-14.1%), they were
      able to generate sufficient torques to perform the task. However, age-related
      differences suggest that chair-rise biomechanics were affected by the reduction
      in muscle strength, and that strength training regimes, particularly for the hip
      musculature, may be important to maintain chair-rise ability in the elderly.
      Copyright 1998 Elsevier Science B.V.

PMID- 10200408
TI  - Increasing obstacle height and decreasing toe-obstacle distance affect the joint
      moments of the stance limb differently when stepping over an obstacle.
AB  - Foot placement during gait is important in regulating the dynamics of the joints
      of the supporting limb and in maintaining balance of the whole body. We
      hypothesized that increasing obstacle height and decreasing toe-obstacle distance
      (distance between the trailing foot and the obstacle during stance of the
      trailing foot just prior to stepping over the obstacle) would affect the joint
      moments of the stance limb differently when stepping over an obstacle. A total of
      14 healthy young adults stepped over an obstacle 51, 102, 153, and 204 mm in
      height in a self-selected manner (i.e. toe-obstacle distance was not controlled)
      and for toe-obstacle distance targets of 10, 20, 30, and 40% of their step
      lengths measured during unobstructed gait. The adduction and internal rotation
      moments at the ankle joint increased as toe-obstacle distance decreased. The
      adduction and internal rotation moments at the hip joint during early stance, the
      internal rotation moment at the knee joint during late stance, and the
      dorsiflexion moment at the ankle joint during late stance increased with obstacle
      height. Reductions in toe-obstacle distance had greater effects on the moments of
      the ankle joint, and increases in obstacle height had greater effects on the
      moments of the hip joint. These greater demands on joint moments may affect the
      abilities of those elderly having decreased muscle strengths to safely step over
      obstacles. Copyright 1998 Elsevier Science B.V.

PMID- 10200409
TI  - A study of the effect of cyproheptadine on gait in hemiplegic children.
AB  - The properties of cyproheptadine as an anti-spastic agent have been reported
      since 1980. In this study we sought to investigate whether gait function, as
      specified by stride length, cadence, heart rate, and also by questionnaire,
      correlated with cyproheptadine medication during a double-blind matched-placebo
      cross-over trial, undertaken on a group of 16 hemiplegic spastic patients aged 4
      18 years. We found that neither qualitative nor quantitative analyses suggested
      any systematic change in gait parameters dependent on cyproheptadine medication.
      We conclude that our study on 16 patients showed no statistical evidence of
      improvement in spasticity due to the action of cyproheptadine. An effect was,
      however, found in the case of mean patient heart rate, which was 10% higher
      (P<0.003) at the end of the cyproheptadine medication period. Copyright 1998
      Elsevier Science B.V.

PMID- 10200410
TI  - Proprioceptive control of posture: a review of new concepts.
AB  - The assumption that proprioceptive inputs from the lower legs are used to trigger
      balance and gait movements is questioned in this review (an outgrowth of
      discussions initiated during the Neural Control of Movement Satellite meeting
      held in Cozumel, Mexico, April 1997). Recent findings presented here suggest that
      trunk or hip inputs may be more important in triggering human balance corrections
      and that proprioceptive input from the lower legs mainly helps with the final
      shaping and intermuscular coordination of postural and gait movements. Three
      major questions were considered. First, what role, if any, do lower-leg
      proprioceptive inputs play in the triggering of normal balance corrections? If
      this role is negligible, which alternative proprioceptive inputs then trigger
      balance corrections? Second, what is the effect of proprioceptive loss on the
      triggering of postural and gait movements? Third, how does proprioceptive loss
      affect the output of central pattern generators in providing the final shaping of
      postural movements? The authors conclude that postural and gait movements are
      centrally organized at two levels. The first level involves the generation of the
      basic directional-specific response pattern based primarily on hip or trunk
      proprioceptive input secondarily on vestibular inputs. This pattern specifies the
      spatial characteristics of muscle activation, that is which muscles are primarily
      activated, as well as intermuscular timing, that is, the sequence in which
      muscles are activated. The second level is involved in the shaping of centrally
      set activation patterns on the basis of multisensorial afferent input (including
      proprioceptive input from all body segments and vestibular sensors) in order that
      movements can adapt to different task conditions. Copyright 1998 Elsevier Science
      B.V.

PMID- 10200411
TI  - Climbing fibres - a key to cerebellar function.

PMID- 10200412
TI  - Kinases, myosin phosphatase and Rho proteins: curiouser and curiouser.

PMID- 10200413
TI  - Molecular insights into the physiology of the 'thin film' of airway surface
      liquid.
AB  - The epithelia that line the airways of the lung exhibit two general functions:
      (1) airway epithelia in all regions 'defend' the lung against infectious and
      noxious agents; and (2) airway epithelia in the proximal regions replenish water
      lost from airway surfaces, i.e. the 'insensible water loss', consequent to
      conditioning inspired air. How airway epithelia perform both functions, and co
      ordinate them in health and disease, is the subject of this review.

PMID- 10200414
TI  - Absence of modulation of the expressed calcium channel alpha1G subunit by
      alpha2delta subunits.
AB  - 1. The modulatory action of the alpha2delta subunit on various high-voltage
      activated calcium channels has been demonstrated previously. However, very little
      is known about auxiliary subunit modulation of low-voltage-activated (LVA)
      calcium channels. We have examined the modulation of the alpha1G subunit
      corresponding to the neuronal T-type calcium channel by the ubiquitously
      expressed alpha2delta-1 and brain-specific alpha2delta-3 subunits. 2. The alpha1G
      subunit was expressed alone or in combination with either the alpha2delta-1 or
      alpha2delta-3 subunit in human embryonic kidney (HEK 293) cells and whole-cell
      barium currents were measured. The current density-voltage relationships for peak
      and sustained current, kinetics of current activation and inactivation, voltage
      dependence of current inactivation and time course of the recovery from
      inactivation were analysed for each type of expressed channel. No significant
      difference was found for any of the examined parameters. 3. These results suggest
      that the LVA alpha1G channel is not regulated by known auxiliary alpha2delta
      subunits.

PMID- 10200415
TI  - Regulation of Na+ pump function by aldosterone is alpha-subunit isoform specific.
AB  - 1. During its early 'genomic' phase of action (< 3 h), aldosterone activates pre
      existing Na+ pumps (Na+,K+-ATPase) in epithelia formed by Xenopus laevis A6
      kidney cells. 2. To test whether this action also applies to pumps containing
      mammalian alpha-subunits of different isoforms, we generated A6 cell lines
      expressing the naturally ouabain-resistant rat alpha1 subunit or the rat alpha2*
      and alpha3* subunits made ouabain resistant by site-directed mutagenesis. 3. Cell
      lines were obtained which expressed the exogenous alpha-subunits in active,
      basolateral Na+ pumps, such that ouabain-resistant pump current (Ip) could be
      measured following apical permeabilization with amphotericin B. 4. The inhibition
      constants (Ki) for ouabain of the current carried by the pumps containing
      exogenous rat alpha-subunits were similar to those reported previously for ATPase
      activity inhibition. The apparent Michaelis constant (Km) for Na+ (K+
      replacement) was slightly higher for pumps containing the rat alpha1 than for
      those containing the alpha2* subunit (34.9 +/- 1.9 versus 26.3 +/- 2.6 mM). 5. At
      a Na+ concentration of 10 mM, aldosterone (2.5 h) increased the pump current
      carried by endogenous pumps as well as that carried by pumps containing the
      exogenous rat alpha1 subunit (by 1.8- to 2.2-fold). In contrast, the current
      carried by pumps containing the exogenous rat alpha2* subunit remained unchanged.
      6. The fact that this early transcriptionally mediated activation of Na+ pumps by
      aldosterone is specific for pumps containing an alpha1 subunit should permit the
      identification in this subunit of structures involved in its regulation.

PMID- 10200416
TI  - Single channel properties of human alpha3 AChRs: impact of beta2, beta4 and
      alpha5 subunits.
AB  - 1. We performed single channel analysis on human alpha3 acetylcholine receptors
      (AChRs) in Xenopus oocytes and native AChRs from the human neuroblastoma cell
      line IMR-32. alpha3 AChRs exhibit channel properties that reflect subunit
      composition. 2. alpha3beta2 AChR open times were 0.71 +/- 0.14 and 3.5 +/- 0.4 ms
      with a predominant conductance of 26 pS. alpha3beta4 AChRs had open times of 1.4
      +/- 0.2 and 6.5 +/- 0.8 ms and a predominant conductance of 31 pS. Burst times
      were 0.82 +/- 0.12 and 5.3 +/- 0.7 ms for alpha3beta2 and 1.7 +/- 0.1 and 16 +/-
      1 ms for alpha3beta4. Desensitization was faster for AChRs with the beta2 subunit
      than for those with the beta4 subunit. 3. One open time for alpha3alpha5beta2
      AChRs (5.5 +/- 0.3 ms) was different from those of alpha3beta2 AChRs. For
      alpha3alpha5beta4 AChRs, an additional conductance, open time and burst time (36
      pS, 22 +/- 3 ms and 43 +/- 4 ms, respectively) were different from those for
      alpha3beta4 AChRs. 4. alpha3 AChRs were inhibited by hexamethonium or
      mecamylamine. The rate constants for block of alpha3beta4 by hexamethonium and of
      alpha3beta2 by mecamylamine were 1.2 x 107 and 4.6 x 107 M-1 s-1, respectively.
      5. AChRs from IMR-32 cells had a predominant conductance of 32 pS and open times
      of 1.5 +/- 0.3 and 9.6 +/- 1.2 ms. These properties were most similar to those of
      alpha3beta4 AChRs expressed in oocytes. Antibodies revealed that 5 +/- 2 % of IMR
      32 alpha3 AChRs contained alpha5 subunits and 6 +/- 2 % contained beta2 subunits.
      IMR-32 alpha3 AChRs are primarily alpha3beta4 AChRs.

PMID- 10200417
TI  - Selective inhibition of gap junction channel activity by synthetic peptides.
AB  - 1. The aim of this study was to inhibit specifically one type of gap junction
      channel in cells expressing multiple connexins (Cx) using synthetic
      oligopeptides. 2. A7r5 cells (an aortic smooth muscle cell line expressing Cx40
      and Cx43) were incubated overnight with synthetic oligopeptides (P180-195)
      corresponding to a segment of the second extracellular loop of Cx43. This segment
      is different in sequence from the corresponding location in Cx40. 3. P180-195
      (500 microM) decreased cell-to-cell coupling as assessed by dye coupling and dual
      whole-cell voltage clamp. The decrease in permeability and junctional conductance
      was caused by selective inhibition of Cx43 gap junction channels. In contrast,
      overnight incubation of A7r5 cells with oligopeptides corresponding to a segment
      of the intracellular cytoplasmic tail of Cx43 was without effect. 4. These
      results indicate that oligopeptides P180-195 may interact with the extracellular
      domain of the Cx43 protein, thereby possibly mimicking connexin-connexin binding.
      This apparently inhibits Cx43 channel activity without disturbing the activity of
      Cx40 channels. 5. Experiments with oligopeptides corresponding to the equivalent
      part of the second extracellular loop of Cx40 (P177-192) pointed towards a
      selective inhibition of Cx40 channel activity. 6. Competition assays using
      synthetic oligopeptides may help to resolve the regulatory properties of gap
      junction channels in primary cells expressing multiple Cx.

PMID- 10200418
TI  - Differential effects of homologous S4 mutations in human skeletal muscle sodium
      channels on deactivation gating from open and inactivated states.
AB  - 1. The outermost charged amino acid of S4 segments in the alpha subunit of human
      skeletal muscle sodium channels was mutated to cysteine in domains I (R219C), II
      (R669C), III (K1126C), and IV (R1448C). Double mutations in DIS4 and DIVS4
      (R219C/R1448C), DIIS4 and DIVS4 (R669C/R1448C), and DIIIS4 and DIVS4
      (K1126C/R1448C) were introduced in other constructs. Macropatch recordings of
      mutant and wild-type (hSkM1-wt) skeletal muscle sodium channels expressed in
      Xenopus oocytes were used to measure deactivation kinetics from open or fast
      inactivated states. 2. Conductance (voltage) curves (G (V)) derived from current
      (voltage) (I (V)) relations indicated a right-shifted G (V) relationship for
      R669C and for R669C/R1448C, but not for other mutations. The apparent valency was
      decreased for all mutations. Time-to-peak activation at -20 mV was increased for
      R1448C and for double mutations. 3. Deactivation kinetics from the open state
      were determined from the monoexponential decay of tail currents. Outermost charge
      to-cysteine mutations in the S4 segments of domains III and IV slowed
      deactivation, with the greatest effect produced by R1448C. The deactivation rate
      constant was slowed to a greater extent for the DIII/DIV double mutation than
      that calculated from additive effects of single mutations in each of these two
      domains. Mutation in DIIS4 accelerated deactivation from the open state, whereas
      mutation in DIS4 had little effect. 4. Delays in the onset to recovery from fast
      inactivation were determined to assess deactivation kinetics from the inactivated
      state. Delay times for R219C and R669C were not significantly different from
      those for hSkM1-wt. Recovery delay was increased for K1126C, and was accelerated
      for R1448C. 5. Homologous charge mutations of S4 segments produced domain
      specific effects on deactivation gating from the open and from the fast
      inactivated state. These results are consistent with the hypothesis that
      translocations of S4 segments in each domain during deactivation are not
      identical and independent processes. Non-identical effects of these mutations
      raise several possibilities regarding deactivation gating; translocation of DIVS4
      may constitute the rate-limiting step in deactivation from the open state, DIVS4
      may be part of the immobilizable charge, and S4 translocations underlying
      deactivation in human skeletal muscle sodium channel may exhibit co-operativity.

PMID- 10200419
TI  - Effects of intra- and extracellular acidifications on single channel Kir2.3
      currents.
AB  - 1. The inward rectifier K+ channel Kir2.3 is inhibited by hypercapnia, and this
      inhibition may be mediated by decreases in intra- and extracellular pH. To
      understand whether Kir2.3 has two distinct pH sensors and whether cytosol-soluble
      factors are involved in the modulation of this channel during intracellular
      acidification, single channel currents were studied by expressing Kir2.3 in
      Xenopus oocytes. 2. In excised inside-out patches, Kir2.3 currents had a high
      baseline channel open-state probability (Po, at pH 7.4) with a strong inward
      rectification. Single channel conductance at hyperpolarizing membrane potential
      was about 17 pS with 150 mM K+ applied to both sides of the membrane. The channel
      showed a substate conductance of about 8 pS. 3. Reduction of intracellular pH
      (pHi) produced a fast and reversible inhibition of single channel Kir2.3 currents
      in inside-out patches. The extent of this inhibition is concentration dependent.
      A clear reduction in Kir2.3 currents was seen at pHi 7.0, and channel activity
      was completely suppressed at pHi 6.2 with mid-point inhibition (pK) at pH 6.77.
      4. The effect of low pHi on Kir2.3 currents was due to a strong inhibition of Po
      and a moderate suppression of single channel conductance. The pK values for these
      single channel properties were pH 6.78 and 6.67, respectively. 5. The decrease in
      Po with low pHi resulted from an increase in the channel mean closed time without
      significant changes in the mean open time. Substate conductance was not seen
      during low pHi. 6. Decrease in extracellular pH (pHo) also caused inhibition of
      single channel activity of Kir2.3 currents in excised outside-out patches. This
      effect, however, was clearly different from that of pHi: the pK (pH 6.70) was
      about 0.1 pH units lower; more than 50 % channel activity was retained at pHo
      5.8; and low pHo affected mainly single channel conductance. 7. These results
      therefore indicate that (1) there are two distinct pH sensors in Kir2.3, (2)
      different mechanisms are involved in the modulation of Kir2.3 through these two
      pH sensors, and (3) cytosol-soluble factors do not appear to be engaged in this
      modulation.

PMID- 10200420
TI  - Metabotropic GABA receptors facilitate L-type and inhibit N-type calcium channels
      in single salamander retinal neurons.
AB  - 1. Whole-cell voltage clamp experiments were performed on isolated spiking
      retinal neurons from the salamander retina. Calcium channel currents were studied
      using barium as the charge carrier while potassium and sodium currents were
      suppressed with TEA and TTX, respectively. 2. Baclofen, a metabotropic GABA
      receptor agonist, both enhanced and suppressed high-voltage-activated calcium
      channel current. Baclofen facilitated an L-type channel current, and this effect
      was not voltage dependent. As reported previously, baclofen inhibited an N-type
      channel current and this action was voltage dependent. 3. While the suppressive
      effect was mediated by a fast-acting, direct G-protein action, the facilitatory
      effect was slower and was blocked by inhibitors of protein kinase C (PKC), either
      GF-109203x or the PKC (19-36) sequence fragment. 4. The pharmacology of the
      inhibitory and facilitatory responses differed. Commonly used antagonists of
      metabotropic GABA receptors, CGP35348 and CGP55845, were more potent antagonists
      of the inhibitory response. Similarly, a selective agonist at the metabotropic
      GABA receptor, APMPA, was also more effective in eliciting the inhibitory
      response. 5. These observations indicate that there may be two baclofen-sensitive
      metabotropic GABA receptors with opposing effects on calcium channel current.
      This is the first description of a facilitatory action of GABAB receptors and
      indicates that GABA may not function exclusively as an inhibitory transmitter.

PMID- 10200421
TI  - Incremental conductance levels of GABAA receptors in dopaminergic neurones of the
      rat substantia nigra pars compacta.
AB  - 1. Molecular and biophysical properties of GABAA receptors of dopaminergic (DA)
      neurones of the pars compacta of the rat substantia nigra were studied in slices
      and after acute dissociation. 2. Single-cell reverse transcriptase-multiplex
      polymerase chain reaction confirmed that DA neurones contained mRNAs encoding for
      the alpha3 subunit of the GABAA receptor, but further showed the presence of
      alpha4 subunit mRNAs. alpha2, beta1 and gamma1 subunit mRNAs were never detected.
      Overall, DA neurones present a pattern of expression of GABAA receptor subunit
      mRNAs containing mainly alpha3/4beta2/3gamma3. 3. Outside-out patches were
      excised from DA neurones and GABAA single-channel patch-clamp currents were
      recorded under low doses (1-5 microM) of GABA or isoguvacine, a selective GABAA
      agonist. Recordings presented several conductance levels which appeared to be
      integer multiples of an elementary conductance of 4-5 pS. This property was
      shared by GABAA receptors of cerebellar Purkinje neurones recorded in slices
      (however, with an elementary conductance of 3 pS). Only the 5-6 lowest levels
      were analysed. 4. A progressive change in the distribution of occupancy of these
      levels was observed when increasing the isoguvacine concentration (up to 10
      microM) as well as when adding zolpidem (20-200 nM), a drug acting at the
      benzodiazepine binding site: both treatments enlarged the occupancy of the
      highest conductance levels, while decreasing that of the smallest ones.
      Conversely, Zn2+ (10 microM), a negative allosteric modulator of GABAA receptor
      channels, decreased the occupancy of the highest levels in favour of the lowest
      ones. 5. These properties of alpha3/4beta2/3gamma3-containing GABAA receptors
      would support the hypothesis of either single GABAA receptor channels with
      multiple open states or that of a synchronous recruitment of GABAA receptor
      channels that could involve their clustering in the membranes of DA neurones.

PMID- 10200423
TI  - Glucocorticoid block of protein kinase C signalling in mouse pituitary
      corticotroph AtT20 D16:16 cells.
AB  - 1. The regulation of large conductance calcium- and voltage-activated potassium
      (BK) currents by activation of the protein kinase C (PKC) and glucocorticoid
      signalling pathways was investigated in AtT20 D16:16 clonal mouse anterior
      pituitary corticotroph cells. 2. Maximal activation of PKC using the phorbol
      esters, 4beta-phorbol 12-myristate, 13-acetate (PMA), phorbol 12, 13 dibutyrate
      (PDBu) and 12-deoxyphorbol 13-phenylacetate (dPPA) elicited a rapid, and
      sustained, inhibition of the outward steady-state voltage- and calcium- dependent
      potassium current predominantly carried through BK channels. 3. The effect of PMA
      was blocked by the PKC inhibitors bisindolylmaleimide I (BIS; 100 nM) and
      chelerythrine chloride (CHE; 25 microM) and was not mimicked by the inactive
      phorbol ester analogue 4alpha-PMA. 4. PMA had no significant effect on the 1 mM
      tetraethylammonium (TEA)-insensitive outward current or pharmacologically
      isolated, high voltage-activated calcium current. 5. PMA had no significant
      effect on steady-state outward current in cells pre-treated for 2 h with 1 microM
      of the glucocorticoid agonist dexamethasone. Dexamethasone had no significant
      effect on steady-state outward current amplitude or sensitivity to 1 mM TEA and
      did not block PMA-induced translocation of the phorbol ester-sensitive PKC
      isoforms, PKCalpha and PKCepsilon, to membrane fractions. 6. Taken together these
      data suggest that in AtT20 D16:16 corticotroph cells BK channels are important
      targets for PKC action and that glucocorticoids inhibit PKC signalling downstream
      of PKC activation.

PMID- 10200422
TI  - Somatic and prejunctional nicotinic receptors in cultured rat sympathetic
      neurones show different agonist profiles.
AB  - 1. The release of [3H]-noradrenaline ([3H]-NA) in response to nicotinic
      acetylcholine receptor (nAChR) agonists was compared with agonist-induced
      currents in cultured rat superior cervical ganglion (SCG) neurones. 2. [3H]-NA
      release in response to high concentrations of nicotinic agonists was reduced, but
      not fully inhibited, by the presence of either tetrodotoxin (TTX) or Cd2+ to
      block voltage-gated Na+ or Ca2+ channels, respectively. We used the component of
      transmitter release that remained in the presence of these substances (named TTX-
      or Cd2+-insensitive release) to pharmacologically characterize nAChRs in
      proximity to the sites of vesicular exocytosis (prejunctional receptors).
      Prejunctional nAChRs were activated by nicotinic agonists with a rank order of
      potency of dimethylphenylpiperazinium iodide (DMPP) > nicotine > cytisine > ACh,
      and with EC50 values ranging from 22 microM (DMPP) to 110 microM (ACh). 3. [3H]
      NA release in response to low concentrations of nAChR agonists was fully
      inhibited by the presence of either TTX or Cd2+ (named TTX- or Cd2+-sensitive
      release). TTX-sensitive release was triggered by nicotinic agonists with a rank
      order of potency of DMPP > cytisine approximately nicotine approximately ACh,
      which due to its similarity to TTX-insensitive release indicates that it might
      also be triggered by prejunctional-type nAChRs. The EC50 values for TTX (Cd2+)
      sensitive release were less than 10 microM for all four agonists. 4. By contrast
      to transmitter release, somatic nAChRs as seen by patch clamp recordings were
      most potently activated by cytisine, with a rank order of potency of cytisine >
      nicotine approximately DMPP > ACh. EC50 values for the induction of currents
      exceeded 20 microM for all four agonists. 5. The nicotinic antagonist
      mecamylamine potently inhibited all transmitter release in response to nicotine.
      alpha-Bungarotoxin (alpha-BuTX) was, on the other hand, without significant
      effect on nicotine-induced TTX-insensitive release. The competitive antagonist
      dihydro-beta-erythroidine (DHbetaE) caused rightward shifts of the dose-response
      curves for both TTX-sensitive and TTX-insensitive transmitter release as well as
      for currents in response to nicotine, with pA2 values ranging from 4.03 to 4.58.
      6. Due to clear differences in the pharmacology of agonists we propose that
      nAChRs of distinct subunit composition are differentially targeted to somatic or
      axonal domains.

PMID- 10200424
TI  - One calcium ion may suffice to open the tetrameric cardiac ryanodine receptor in
      rat ventricular myocytes.
AB  - 1. The release of Ca2+ from sarcoplasmic reticulum in response to Ca2+ entering
      through L-type Ca2+ channels was studied in isolated voltage clamped rat
      ventricular myocytes at room temperature using the fluorescent Ca2+ indicators
      fluo-3 and Oregon Green 488 Bapta 5N. 2. Depolarizations to positive potentials
      elicited fluo-3 Ca2+ transients with rates of rise that were linearly related to
      the magnitude of the peak measured Ca2+ current in the presence of Cs+-containing
      pipette solutions. 3. Further experiments utilizing prepulses to preactivate a
      constant number of channels also revealed a linear relationship between the Ca2+
      transient rate of rise and the magnitude of entering Ca2+ current at positive
      potentials. Under these conditions as well, the maximal rates of rise of global
      myoplasmic Ca2+ transients were due primarily to Ca2+ release from the
      sarcoplasmic reticulum as revealed by effects of ryanodine and caffeine on the
      Ca2+ transients. Using such prepulses, linearity between the Ca2+ transient rate
      of rise and the magnitude of the peak Ca2+ current was found under a variety of
      pulse protocols. 4. Using one such pulse protocol, linearity between the Ca2+
      transient rate of rise and the magnitude of the peak Ca2+ current was also found
      when Ca2+ currents assessed at one potential were reduced in magnitude during the
      onset of block by application of Co2+. Using the same pulse protocol, linearity
      between the Ca2+ transient rate of rise and the magnitude of the peak Ca2+
      current was also found when use of Cs+ was avoided by blocking K+ currents with
      extracellular TEA and 4-aminopyridine. Linearity in the relationship between the
      Ca2+ transient rate of rise and the magnitude of the peak Ca2+ current was also
      found when Ca2+ transients were measured using the low affinity Ca2+ indicator
      Oregon Green 488 Bapta 5N in place of fluo-3. 5. These results appear to indicate
      that the cardiac ryanodine receptor is capable of being activated by only one
      calcium ion. Alternative interpretations of the data are discussed.

PMID- 10200425
TI  - Beta-adrenergic agonists regulate cell membrane fluctuations of human
      erythrocytes.
AB  - 1. Mechanical fluctuations of the cell membrane (CMFs) in human erythrocytes
      reflect the bending deformability of the membrane-skeleton complex. These
      fluctuations were monitored by time-dependent light scattering from a small area
      ( approximately 0. 25 microm2) of the cell surface by a method based on point
      dark field microscopy. 2. Exposure of red blood cells (RBCs) to adrenaline
      (epinephrine) and isoproterenol (isoprenaline) resulted in up to a 45 % increase
      in the maximal fluctuation amplitude and up to a 35 % increase in the half-width
      of the amplitude distribution. The power spectra of membrane fluctuations of
      control and treated cells revealed that adrenaline stimulated only the low
      frequency component (0.3-3 Hz). Analysis of the dose-response curves of beta
      adrenergic agonists yielded an EC50 of 5 x 10-9 and 1 x 10-11 M for adrenaline
      and isoproterenol, respectively. Propranolol had an inhibitory effect on the
      stimulatory effect of isoproterenol. These findings show a potency order of
      propranolol > isoproterenol > adrenaline. 3. The stimulatory effect of adrenaline
      was a temporal one, reaching its maximal level after 20-30 min but being
      abolished after 60 min. However, in the presence of 3-isobutyl-1-methylxanthine,
      a partial stimulatory effect was maintained even after 60 min. Pentoxifylline and
      8-bromo-cAMP elevated CMFs. However, exposure of ATP-depleted erythrocytes to
      adrenaline or 8-bromo-cAMP did not yield any elevation in CMFs. These findings
      suggest that the beta-agonist effect on CMFs is transduced via a cAMP-dependent
      pathway. 4. Deoxygenation decreased CMFs and filterability of erythrocytes by
      approximately 30 %. The stimulatory effect of isoproterenol on CMFs was 2.2-fold
      higher in deoxygenated RBCs than in oxygenated cells. 5. Exposure of RBCs to
      adrenaline resulted in a concentration-dependent increase in RBC filterability,
      demonstrating a linear relationship between CMFs and filterability, under the
      same exposure conditions to adrenaline. These findings suggest that beta
      adrenergic agonists may improve passage of erythrocytes through microvasculature,
      enhancing oxygen delivery to tissues, especially under situations of reduced
      oxygen tension for periods longer than 20 min.

PMID- 10200426
TI  - How does beta-adrenergic stimulation increase the heart rate? The role of
      intracellular Ca2+ release in amphibian pacemaker cells.
AB  - 1. The mechanism by which sympathetic transmitters increase the firing rate of
      pacemaker cells was explored in isolated cells from the sinus venosus of the cane
      toad Bufo marinus. Intracellular calcium concentration ([Ca2+]i) was measured
      with indo-1 and membrane potential and currents were recorded with the nystatin
      perforated-patch technique. 2. Adrenaline or isoprenaline (2 microM) increased
      the transient rise in [Ca2+]i and increased the firing rate; these effects were
      blocked by propranolol (2 microM). 3. To determine whether the changes in [Ca2+]i
      might influence the firing rate we studied agents which affect either the loading
      or the release of Ca2+ from the sarcoplasmic reticulum (SR). Rapid application of
      caffeine (10 mM) to spontaneously firing cells caused a large Ca2+ release from
      the SR and the cells were then quiescent for 24 s. In the presence of beta
      adrenergic stimulation the caffeine-induced [Ca2+]i was 14 % larger but the
      period of quiescence after application was reduced to 12 s. 4. Ryanodine, at
      either low (1 microM) or high (> 10 microM) concentration, stopped firing.
      However, when the SR store content of Ca2+ was tested with caffeine, at low
      ryanodine concentration the SR Ca2+ store was empty whereas at the high
      concentration the SR store was still loaded with Ca2+. beta-Adrenergic
      stimulation was not able to restore firing at the low concentration of ryanodine
      but did restore firing at the high ryanodine concentration. 5. An SR Ca2+ pump
      blocker, 2, 5-di(tert-butyl)-1,4-hydroquinone (TBQ) which depletes the SR store
      of Ca2+, also rapidly and reversibly stopped spontaneous firing. 6. The relation
      between the amplitude of the [Ca2+]i transient and firing rate established in the
      presence of ryanodine was similar when firing was restored by beta-stimulation.
      7. In both spontaneously firing and voltage-clamped cells, depleting the SR store
      with either ryanodine or TBQ suggested that about half of the Ca2+ which
      contributes to the calcium transient is released from the SR. 8. These results
      show that the amplitude of the [Ca2+]i transient is an important factor in the
      firing rate of toad pacemaker cells and consequently agents which modify SR Ca2+
      release influence firing rate. The effects of beta-stimulation on firing rate
      seem to be largely mediated by changes in amplitude of the [Ca2+]i transient.

PMID- 10200427
TI  - Ca2+-independent phosphorylation of myosin in rat caudal artery and chicken
      gizzard myofilaments.
AB  - 1. Smooth muscle contraction is activated primarily by the Ca2+-calmodulin (CaM)
      dependent phosphorylation of the 20 kDa light chains (LC20) of myosin. Activation
      can also occur in some instances without a change in intracellular free [Ca2+] or
      indeed in a Ca2+-independent manner. These signalling pathways often involve
      inhibition of myosin light chain phosphatase and unmasking of basal kinase
      activity leading to LC20 phosphorylation and contraction. 2. We have used
      demembranated rat caudal arterial smooth muscle strips and isolated chicken
      gizzard myofilaments in conjunction with the phosphatase inhibitor microcystin-LR
      to investigate the mechanism of Ca2+-independent phosphorylation of LC20 and
      contraction. 3. Treatment of Triton X-100-demembranated rat caudal arterial
      smooth muscle strips with microcystin at pCa 9 triggered a concentration
      dependent contraction that was slower than that induced by pCa 4.5 or 6 but
      reached comparable steady-state levels of tension. 4. This Ca2+-independent,
      microcystin-induced contraction correlated with phosphorylation of LC20 at serine
      19 and threonine-18. 5. Whereas Ca2+-dependent LC20 phosphorylation and
      contraction were inhibited by a synthetic peptide (AV25) based on the
      autoinhibitory domain of myosin light chain kinase (MLCK), Ca2+-independent,
      microcystin-induced LC20 phosphorylation and contraction were resistant to AV25.
      6. Ca2+-independent LC20 kinase activity was also detected in chicken gizzard
      smooth muscle myofilaments and catalysed phosphorylation of endogenous myosin
      LC20 at serine-19 and/or threonine-18. This is in contrast to MLCK which
      phosphorylates threonine-18 only after prior phosphorylation of serine-19. 7.
      Gizzard Ca2+-independent LC20 kinase could be separated from MLCK by differential
      extraction from myofilaments and by CaM affinity chromatography. Its activity was
      resistant to AV25. 8. We conclude that inhibition of smooth muscle myosin light
      chain phosphatase (MLCP) unmasks the activity of a Ca2+-independent LC20 kinase
      associated with the myofilaments and distinct from MLCK. This kinase, therefore,
      probably plays a role in Ca2+ sensitization and Ca2+-independent contraction of
      smooth muscle in response to stimuli that act via Ca2+-independent pathways,
      leading to inhibition of MLCP.

PMID- 10200428
TI  - The Rho-related protein Rnd1 inhibits Ca2+ sensitization of rat smooth muscle.
AB  - 1. The small GTP-binding Rho proteins are involved in the agonist-induced Ca2+
      sensitization of smooth muscle. The action and the expression of Rnd1, a new
      member of the Rho protein family constitutively bound to GTP, has been studied in
      rat smooth muscle. 2. Recombinant prenylated Rnd1 (0.01-0.1 mg ml-1) dose
      dependently inhibited carbachol- and GTPgammaS-induced Ca2+ sensitization in beta
      escin-permeabilized ileal smooth muscle strips but had no effect on the tension
      at submaximal [Ca2+] (pCa 6.3). Rnd1 inhibited GTPgammaS-induced tension without
      shifting the dose-response curves to GTPgammaS. 3. pCa-tension relationships were
      not modified by Rnd1 and the rise in tension induced through the inhibition of
      myosin light chain phosphatase by calyculin A was not affected by Rnd1. 4. The
      Ca2+ sensitization induced by recombinant RhoA was completely abolished when RhoA
      and Rnd1 were applied together. 5. Rnd1 was expressed at a low level in membrane
      fractions prepared from intestinal or arterial smooth muscles. The expression of
      Rnd1 was strongly increased in ileal and aortic smooth muscle from rats treated
      with progesterone or oestrogen. Progesterone-treated ileal muscle strips showed a
      decrease in agonist-induced Ca2+ sensitization. 6. The present study shows that
      (i) Rnd1 inhibits agonist- and GTPgammaS-induced Ca2+ sensitization of smooth
      muscle by specifically interfering with a RhoA-dependent mechanism and (ii) an
      increase in Rnd1 expression may account, at least in part, for the steroid
      induced decrease in agonist-induced Ca2+ sensitization.

PMID- 10200429
TI  - Role of PI3-kinase in the development of interstitial cells and pacemaking in
      murine gastrointestinal smooth muscle.
AB  - 1. Development of the pacemaker system in the small intestine depends upon
      signalling via tyrosine kinase (Kit) receptors. The downstream pathways initiated
      by Kit in interstitial cells of Cajal (ICC) have not been investigated.
      Wortmannin and 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY 294002),
      inhibitors of phosphatidylinositol 3'-kinase (PI3-kinase), were used to test the
      involvement of this pathway in the development and maintenance of ICC and
      electrical rhythmicity in the murine small intestine. 2. ICC and electrical slow
      waves were present in the murine jejunum at birth. ICC and electrical rhythmicity
      continued to develop in neonates such that adult activity was recorded after 1
      week. Development of ICC and rhythmicity were maintained in organ culture. 3.
      Wortmannin or LY 294002 inhibited the development of slow waves and blocked
      rhythmicity within 2-4 days. Loss of slow waves was preceded by disappearance of
      Kit-positive cells from the myenteric (IC-MY) and deep muscular plexus (IC-DMP)
      regions. Wortmannin or LY 294002 had no acute effect on slow waves. 4. Muscles
      from older animals (day 10-day 30) developed resistance to wortmannin treatment,
      but when the exposure to wortmannin was increased to 35 days, damage to ICC
      networks and electrical dysrhythmias were observed. 5. PI3-kinase appears to be a
      critical downstream signalling element linking Kit receptors to ICC development
      and maintenance of phenotype. ICC are more sensitive to Kit or PI3-kinase
      blockade at birth, but the importance of the PI3-kinase signalling in the
      maintenance of ICC persists into adulthood. Interference with PI3-kinase
      signalling in immature or adult animals could result in disruption of ICC and
      gastrointestinal dysrhythmias.

PMID- 10200430
TI  - Modulation by substrate concentration of maximal shortening velocity and
      isometric force in single myofibrils from frog and rabbit fast skeletal muscle.
AB  - 1. The effects of magnesium adenosine triphosphate (MgATP; also referred to as
      'substrate') concentration on maximal force and shortening velocity have been
      studied at 5 C in single and thin bundles of striated muscle myofibrils. The
      minute diameters of the preparations promote rapid diffusional equilibrium
      between the bathing medium and lattice space so that during contraction fine
      control of substrate and product concentrations is achieved. 2. Myofibrils from
      frog tibialis anterior and rabbit psoas fast skeletal muscles were activated
      maximally by rapidly (10 ms) exchanging a continuous flux of pCa 8.0 for one at
      pCa 4.75 at a range of substrate concentrations from 10 microM to 5 mM. At high
      substrate concentrations maximal isometric tension and shortening velocity of
      both frog and rabbit myofibrils were very close to those determined in whole
      fibre preparations from the same muscle types. 3. As in frog and rabbit skinned
      whole fibres, the maximal isometric force of the myofibril preparations decreases
      as MgATP concentration is increased. The maximal velocity of unloaded shortening
      (V0) depends hyperbolically on substrate concentration. V0 extrapolated to
      infinite MgATP (3.6 +/- 0.2 and 0.8 +/- 0.03 l0 s-1 in frog and rabbit
      myofibrils, respectively) is very close to that determined directly at high
      substrate concentration. The Km is 210 +/- 20 microM for frog tibialis anterior
      and 120 +/- 10 microM for rabbit psoas myofibrils, values about half those found
      in larger whole fibre preparations of the same muscle types. This implies that
      measurements in whole skinned fibres are perturbed by diffusional delays, even in
      the presence of MgATP regenerating systems. 4. In both frog and rabbit
      myofibrils, the Km for V0 is about one order of magnitude higher than the Km for
      myofibrillar MgATPase determined biochemically in the same experimental
      conditions. This confirms that the difference between the Km values for MgATPase
      and shortening velocity is a basic feature of the mechanism of chemomechanical
      transduction in muscle contraction.

PMID- 10200431
TI  - Inositol 1,3,4,5-tetrakisphosphate enhances long-term potentiation by regulating
      Ca2+ entry in rat hippocampus.
AB  - 1. The effect of inositol 1,3,4,5-tetrakisphosphate (InsP4) on long-term
      potentiation (LTP) was investigated in the CA1 region of rat hippocampal slices.
      Intracellular application of InsP4 and EPSP recordings were carried out using the
      whole-cell configuration. 2. Induction of LTP in the presence of InsP4 (100
      microM) resulted in a substantial enhancement of the LTP magnitude compared with
      control potentiation. Using an intrapipette perfusion system, it was established
      that application of InsP4 was required during induction of potentiation for this
      enhancement to occur. An enhancement of LTP was not observed if a non
      metabolizable inositol 1,4,5-trisphosphate (InsP3) analogue (2,3-dideoxy-1,4,5
      trisphosphate, 100 microM) was applied intracellularly. 3. Current-voltage
      relations of NMDA receptor-mediated EPSCs were not altered by InsP4 application.
      The presence of InsP4 was slightly effective in relieving a D-(-)-2-amino-5
      phosphonopentanoic acid (D-APV)-induced block of LTP. 4. The peak current
      amplitude of voltage-gated calcium channels (VGCCs) was increased by InsP4. omega
      Conotoxin GVIA inhibited the InsP4-induced LTP facilitation. 5. These data
      indicate that InsP4 can modify the extracellular Ca2+ entry through upregulation
      of VGCCs, which may in turn contribute to the observed enhancement of LTP induced
      by InsP4. 6. To investigate the possible involvement of intracellular Ca2+
      release in the facilitatory effect of InsP4 on LTP, different inhibitors of the
      endoplasmic reticulum-dependent Ca2+ release were applied (heparin, ryanodine,
      cyclopiazonic acid). The results suggest that InsP4 activates postsynaptic InsP3
      dependent Ca2+ release which normally does not contribute to the calcium-induced
      calcium release-dependent LTP.

PMID- 10200432
TI  - Reciprocity between light intensity and rhodopsin concentration across the rat
      retina.
AB  - 1. If a purpose of photostasis - absorption of a constant number of photons by
      the retina, regardless of incident light levels - is to maintain rods at
      saturation during the light period, then in retinal regions where light intensity
      is low, rhodopsin concentration should be high, and vice versa. 2. Our ocular
      transmission photometric measurements revealed that the distribution of light
      intensity across the rat retina was not as simple as had been thought and,
      furthermore, that the local concentration of rhodopsin had a high negative
      correlation with the light intensity. 3. The reciprocity between these two
      parameters leads to nearly uniform rates of photon absorption in rods across the
      retina.

PMID- 10200433
TI  - Gating of transmission in climbing fibre paths to cerebellar cortical C1 and C3
      zones in the rostral paramedian lobule during locomotion in the cat.
AB  - 1. Climbing fibre field potentials evoked by low intensity (non-noxious)
      electrical stimulation of the ipsilateral superficial radial nerve have been
      recorded in the rostral paramedian lobule (PML) in awake cats. Chronically
      implanted microwires were used to monitor the responses at eight different C1 and
      C3 zone sites during quiet rest and during steady walking on a moving belt. The
      latency and other characteristics of the responses identified them as mediated
      mainly via the dorsal funiculus-spino-olivocerebellar path (DF-SOCP). 2. At each
      site, mean size of response (measured as the area under the field, in mV ms)
      varied systematically during the step cycle without parallel fluctuations in size
      of the peripheral nerve volley. Largest responses occurred overwhelmingly during
      the stance phase of the step cycle in the ipsilateral forelimb while smallest
      responses occurred most frequently during swing. 3. Simultaneous recording from
      pairs of C1 zone sites located in the anterior lobe (lobule V) and C1 or C3 zone
      sites in rostral PML revealed markedly different patterns of step-related
      modulation. 4. The findings shed light on the extent to which the SOCPs
      projecting to different parts of a given zone can be regarded as functionally
      uniform and have implications as to their reliability as channels for conveying
      peripheral signals to the cerebellum during locomotion.

PMID- 10200434
TI  - Contribution of baroreceptors and chemoreceptors to ventricular hypertrophy
      produced by sino-aortic denervation in rats.
AB  - 1. To test whether sino-aortic denervation (SAD)-induced right ventricular
      hypertrophy (RVH) is a consequence of baroreceptor or chemoreceptor denervation,
      we compared the effects of aortic denervation (AD), carotid denervation (CD), SAD
      and a SAD procedure modified to spare the carotid chemoreceptors (mSAD), 6 weeks
      after denervation surgery in rats. A sham surgery group served as the control. 2.
      The blood pressure (BP) level was unaffected by AD, CD or SAD, but increased (9
      %) following mSAD. The mean heart rate level was not affected. Short-term BP
      variability was elevated following AD (81 %), SAD (144 %) and mSAD (146 %), but
      not after CD. Baroreflex heart rate responses to phenylephrine were attenuated in
      all denervation groups. 3. Significant RVH occurred only following CD and SAD.
      These procedures also produced high mortality (CD and SAD) and significant
      increases in right ventricular pressures and haematocrit (CD). 4. Significant
      left ventricular hypertrophy occurred following CD, SAD and mSAD. Normalized left
      ventricular weight was significantly correlated with indices of BP variability.
      5. These results suggest that SAD-induced RVH is a consequence of chemoreceptor,
      not baroreceptor, denervation. Our results also demonstrate that a mSAD procedure
      designed to spare the carotid chemoreceptors produced profound baroreflex
      dysfunction and significant left, but not right, ventricular hypertrophy.

PMID- 10200435
TI  - Modality-specific hyper-responsivity of regenerated cat cutaneous nociceptors.
AB  - 1. Experiments were performed on anaesthetized cats to investigate the receptive
      properties of regenerated cutaneous tibial nerve nociceptors, and to obtain
      evidence for coupling between them and other afferent fibres as being possible
      peripheral mechanisms involved in neuropathic pain. These properties were studied
      6-7 months after nerve section and repair. 2. Recordings were made from 25
      regenerated nociceptors; 14 were A fibres and the remainder were C fibres. Their
      receptive field sizes and conduction velocities were similar to controls. There
      was no significant difference between their mechanical thresholds and those of a
      control population of nociceptors. 3. Regenerated nociceptors were significantly
      more responsive to suprathreshold mechanical stimuli than were uninjured control
      fibres. This increase in mechanical sensitivity occurred in both A and C fibres,
      although A fibres showed a greater increase in mechano-sensitivity than C fibres.
      Over half of the regenerated nociceptors (13/25) showed after-discharge to
      mechanical stimuli which was never seen in controls; the mean firing rate during
      this period of after-discharge was significantly related to both stimulus
      intensity and stimulus area. 4. There was no significant difference between the
      heat encoding properties of regenerated nociceptors and control nociceptors. Cold
      sensitivity was similarly unchanged. Thus, abnormal peripheral sprouting was
      unlikely to account for the increased mechanical sensitivity of the regenerated
      fibres. None of the regenerated nociceptors were found to be coupled to other
      fibres. 5. These results suggest that the clinical observation of mechanical
      hyperalgesia in patients after nerve injury may have a peripheral basis. Based on
      this model, other signs of neuropathic pain (i.e. tactile or thermal allodynia)
      are more likely to be due to altered central processing.

PMID- 10200436
TI  - Functional heterogeneity of corticotrophs in the anterior pituitary of the sheep
      fetus.
AB  - 1. Parturition in the sheep is dependent on prepartum stimulation of the
      hypothalamo-pituitary-adrenal axis and an increase in fetal plasma cortisol
      concentration. We have investigated whether there are changes in the functional
      characteristics of the corticotrophic cells in the week before delivery or in
      response to an increase in circulating cortisol. 2. Fetal sheep were infused with
      cortisol (2-3 mg 24 h-1 i.v.; n = 11), or saline (4.4 ml 24 h-1 i.v.; n = 10)
      between 109 and 116 days gestation and pituitary glands were collected from these
      two groups, and from a late gestational group (140-145 days gestation; n = 10)
      for cell culture. Cells in half the wells from each pituitary were treated with
      cytotoxin (Cx; a cytotoxic analogue of corticotrophin releasing hormone (CRH)) to
      eliminate CRH target cells before exposure to ovine (o)CRH (10-8 M), arginine
      vasopressin (AVP; 10-7 M) or oCRH + AVP. 3. We have demonstrated that around 70 %
      of adrenocorticotrophic hormone (ACTH) in the fetal anterior pituitary is stored
      within corticotrophs which are CRH responsive. Cortisol acts to inhibit ACTH
      synthesis in corticotrophic cells which are CRH responsive, whereas AVP
      responsive cells in the fetal pituitary are relatively resistant to cortisol. 4.
      We propose that the stimulatory influence of the fetal hypothalamus must
      counteract the negative feedback effect of cortisol in the CRH-responsive cells
      to stimulate the increase in pituitary ACTH output which occurs before delivery.

PMID- 10200437
TI  - Effect of a 17 day spaceflight on contractile properties of human soleus muscle
      fibres.
AB  - 1. Soleus biopsies were obtained from four male astronauts 45 days before and
      within 2 h after a 17 day spaceflight. 2. For all astronauts, single chemically
      skinned post-flight fibres expressing only type I myosin heavy chain (MHC)
      developed less average peak Ca2+ activated force (Po) during fixed-end
      contractions (0.78 +/- 0. 02 vs. 0.99 +/- 0.03 mN) and shortened at a greater
      mean velocity during unloaded contractions (Vo) (0.83 +/- 0.02 vs. 0.64 +/- 0.02
      fibre lengths s-1) than pre-flight type I fibres. 3. The flight-induced decline
      in absolute Po was attributed to reductions in fibre diameter and/or Po per fibre
      cross-sectional area. Fibres from the astronaut who experienced the greatest
      relative loss of peak force also displayed a reduction in Ca2+ sensitivity. 4.
      The elevated Vo of the post-flight slow type I fibres could not be explained by
      alterations in myosin heavy or light chain composition. One alternative
      possibility is that the elevated Vo resulted from an increased myofilament
      lattice spacing. This hypothesis was supported by electron micrographic analysis
      demonstrating a reduction in thin filament density post-flight. 5. Post-flight
      fibres shortened at 30 % higher velocities than pre-flight fibres at external
      loads associated with peak power output. This increase in shortening velocity
      either reduced (2 astronauts) or prevented (2 astronauts) a post-flight loss in
      fibre absolute peak power (microN (fibre length) s-1). 6. The changes in soleus
      fibre diameter and function following spaceflight were similar to those observed
      after 17 days of bed rest. Although in-flight exercise countermeasures probably
      reduced the effects of microgravity, the results support the idea that ground
      based bed rest can serve as a model of human spaceflight. 7. In conclusion, 17
      days of spaceflight decreased force and increased shortening velocity of single
      Ca2+-activated muscle cells expressing type I MHC. The increase in shortening
      velocity greatly reduced the impact that impaired force production had on
      absolute peak power.

PMID- 10200438
TI  - Patterned ballistic movements triggered by a startle in healthy humans.
AB  - 1. The reaction time to a visual stimulus shortens significantly when an
      unexpected acoustic startle is delivered together with the 'go' signal in healthy
      human subjects. In this paper we have investigated the physiological mechanisms
      underlying this effect. If the commands for the startle and the voluntary
      reaction were superimposed at some level in the CNS, then we would expect to see
      alterations in the configuration of the voluntary response. Conversely, if the
      circuit activated by the startling stimulus is somehow involved in the execution
      of voluntary movements, then reaction time would be sped up but the configuration
      of the motor programme would be preserved. 2. Fourteen healthy male and female
      volunteers were instructed to react as fast as possible to a visual 'go' signal
      by flexing or extending their wrist, or rising onto tiptoe from a standing
      position. These movements generated consistent and characteristic patterns of EMG
      activation. In random trials, the 'go' signal was accompanied by a very loud
      acoustic stimulus. This stimulus was sufficient to produce a startle reflex when
      given unexpectedly on its own. 3. The startling stimulus almost halved the
      latency of the voluntary response but did not change the configuration of the EMG
      pattern in either the arm or the leg. In some subjects the reaction times were
      shorter than the calculated minimum time for processing of sensory information at
      the cerebral cortex. Most subjects reported that the very rapid responses were
      produced by something other than their own will. 4. We conclude that the very
      short reaction times were not produced by an early startle reflex adding on to a
      later voluntary response. This would have changed the form of the EMG pattern
      associated with the voluntary response. Instead, we suggest that such rapid
      reactions were triggered entirely by activity at subcortical levels, probably
      involving the startle circuit. 5. The implication is that instructions for
      voluntary movement can in some circumstances be stored and released from
      subcortical structures.

PMID- 10200439
TI  - When complex worlds collide: retinoic acid and apoptosis.

PMID- 10200440
TI  - Retinoic acids regulate apoptosis of T lymphocytes through an interplay between
      RAR and RXR receptors.
AB  - Vitamin A deficiency has been known for a long time to be accompanied with immune
      deficiency and susceptibility to a wide range of infectious diseases. Increasing
      evidence suggests that retinoic acids derived from vitamin A are involved in the
      functional regulation of the immune system. Of the two groups of retinoid
      receptors, retinoic acid receptors (RARs) and retinoid X receptors (RXRs) all
      trans and 9-cis retinoic acids are high affinity ligands for RARs and 9-cis
      retinoic acid additionally binds to RXRs. In cells, at high concentrations, all
      trans retinoic acid can be converted to 9-cis retinoic acid by unknown
      mechanisms. Apoptosis plays a major role in shaping the T cell repertoire and one
      way in which retinoids may affect immune functions is to influence the various
      apoptosis pathways. Indeed, it has been shown that retinoic acids can induce
      apoptosis, increase the rate of dexamethasone-induced death and inhibit
      activation-induced death of thymocytes and T lymphocytes. Therefore, retinoids
      together with glucocorticoids may be involved in regulating positive and negative
      selection of T lymphocytes. Here we demonstrate that retinoids can induce
      apoptosis of T cells through the stimulation of RARgamma. Specific stimulation of
      RARalpha, on the other hand, prevents both RARgamma-dependent and TCR-mediated
      cell death. In all these functions 9-cis retinoic acid proved to be more
      effective than all-trans retinoic acid suggesting the involvement of RXRs. Based
      on these results a possible mechanism through which costimulation of RARs and
      RXRs might affect spontaneous and activation-induced death of T lymphocytes is
      proposed.

PMID- 10200441
TI  - Retinoid-induced apoptosis in normal and neoplastic tissues.
AB  - Vitamin A and its derivatives (collectively referred to as retinoids) are
      required for many fundamental life processes, including vision, reproduction,
      metabolism, cellular differentiation, hematopoesis, bone development, and pattern
      formation during embryogenesis. There is also considerable evidence to suggest
      that natural and synthetic retinoids have therapeutical effects due to their
      antiproliferative and apoptosis-inducing effects in human diseases such as
      cancer. Therefore it is not surprising that a significant amount of research was
      dedicated to probe the molecular and cellular mechanisms of retinoid action
      during the past decade. One of the cellular mechanisms retinoids have been
      implicated in is the initiation and modulation of apoptosis in normal development
      and disease. This review provides a brief overview of the molecular basis of
      retinoid signaling, and focuses on the retinoid-regulation of apoptotic cell
      death and gene expression during normal development and in pathological
      conditions in vivo and in various tumor cell lines in vitro.

PMID- 10200442
TI  - The induction of apoptosis in HeLa cells by the loss of LBP-p40.
AB  - To analyze the function of the laminin-binding protein precursor p40 (LBP-p40) in
      higher eukaryotic cells, plasmid DNA expressing antisense or sense cDNA for p40
      under the control of the LacSwitch system was introduced into HeLa cells. Stable
      transformants were isolated, and the expression of p40 was assayed by Western and
      Northern blotting. The expression level of p40 was not affected in HeLa cell
      transformants cultured in 10% serum-supplemented media with the induction of
      antisense (AS)-p40 with 5 mM IPTG. However, both the protein and message for
      endogenous p40 in serum-depleted media with 5 mM IPTG were reduced to about 30 -
      10% of the expression level in serum-free media without 5 mM IPTG. Colony
      formation was inhibited with the suppression of p40. AS-p40 clones died in 7 days
      when cultured in serum-depleted media with 5 mM IPTG, while clones without 5 mM
      IPTG AS-p40 clones never died, even in serum-depleted media. Additionally, sense
      (S)-p40 clones and control CAT clones survived more than 2 weeks in serum-free
      media with 5 mM IPTG. DNA fragmentation assay revealed that cell death induced by
      the reduction of AS-p40 resulted from apoptosis. Both the inhibition of cell
      growth and apoptotic cell death were partially rescued by the transfer of the p40
      cDNA expression vector to AS-p40 clones. Moreover, the introduction of a
      synthetic hammerhead ribozyme for LBP-p40 using a fusigenic viral liposome
      suppressed the message for LBP-p40 even in the presence of 10% serum, and it also
      induced apoptosis.

PMID- 10200443
TI  - Fas/CD95/Apo-I activates the acidic sphingomyelinase via caspases.
AB  - Fas/CD95/Apo-I has been shown to stimulate a variety of molecules including
      several members of the caspase family and the acidic sphingomyelinase (Martin and
      Green 1995; Gulbins et al, 1995). Here, we demonstrate that Fas receptor
      triggered activation of the acidic sphingomyelinase, consumption of
      sphingomyelin, release of ceramide, and subsequent activation of JNK and p38-K
      are regulated by caspases. Inhibition of caspases by Ac-YVAD-chloromethylketone
      or transient CrmA transfection prevented stimulation of acidic sphingomyelinase,
      release of ceramide and activation of JNK and p38-K upon Fas-receptor
      crosslinking. Likewise, Fas triggered apoptosis was almost completely blocked by
      Ac-YVAD-chloromethylketone or CrmA mediated inhibition of caspases. The results
      suggest a new signalling cascade from the Fas receptor via caspases to acidic
      sphingomyelinase, ceramide and JNK/p38-K.

PMID- 10200444
TI  - High and low molecular weight DNA cleavage in ovarian granulosa cells:
      characterization and protease modulation in intact cells and in cell-free nuclear
      autodigestion assays.
AB  - To continue elucidation of the biochemical and molecular pathways involved in the
      induction of apoptosis in granulosa cells (GC) of ovarian follicles destined for
      atresia, we characterized the occurrence and protease modulation of high and low
      molecular weight (MW) DNA fragmentation during rat GC death. Atresia of ovarian
      follicles, occurring either spontaneously in vivo or induced in vitro, was
      associated with both high MW and internucleosomal (low MW) DNA cleavage.
      Incubation of follicles in the presence of a putative irreversible and non
      competitive inhibitor of caspase-1 (interleukin-1beta-converting enzyme or ICE),
      sodium aurothiomalate (SAM), completely prevented internucleosomal, but not high
      MW, DNA cleavage. As reported previously, morphological features of apoptosis
      (pyknosis, cellular condensation) and atresia (granulosa cell disorganization,
      oocyte pseudomaturation) remained detectable in SAM-treated follicles. The
      potential involvement of proteases in endonuclease activation was further
      analyzed in cell-free assays using nuclei from both GC (which autodigest their
      DNA) and HeLa cells (HC, which do not autodigest their DNA unless incubated with
      extracts prepared from other cell types). Crude cytoplasmic extracts prepared
      from GC induced both high MW and internucleosomal DNA cleavage in HC nuclei. The
      induction of low, but not high, MW DNA cleavage in HC nuclei by GC extracts was
      suppressed by pretreatment of the extracts with SAM or with any one of the serine
      protease inhibitors, dichloroisocoumarin (DCI), N-tosyl-L
      leucylchloromethylketone (TLCK) or N-tosyl-L-phenylchloromethylketone (TPCK).
      Interestingly, SAM and DCI also prevented cation-induced low MW DNA fragmentation
      in GC nuclei; however, TLCK and TPCK were without effect. Our results support a
      role for cytoplasmic and nuclear serine proteases in the activation of the
      endonuclease(s) responsible for internucleosomal DNA cleavage during apoptosis.

PMID- 10200445
TI  - Virus infection induces neuronal apoptosis: A comparison with trophic factor
      withdrawal.
AB  - Multicellular organisms can employ a number of defences to combat viral
      replication, the most dramatic being implementation of a cell autonomous
      apoptotic process. The overall cost to the viability of an organism of losing
      infected cells by apoptosis may be small if the dying cells can be substituted.
      In contrast, suicide of irreplaceable cells such as highly specialised neurons
      may have a more dramatic, even fatal consequence. Previous in vitro approaches to
      understanding whether neurotropic viruses cause neurons to apoptose have utilised
      transformed cell lines. These are not in the appropriate state of differentiation
      to provide an accurate indication of events in vivo. We have chosen to
      characterise the ability of a model CNS disease-causing virus, Semliki Forest
      virus (SFV), to infect and trigger apoptosis in primary cultures of nerve growth
      factor (NGF)-dependent sensory neurons. These cells are known to die when
      deprived of NGF and constitute a useful indicator of apoptosis. We observe that
      infection causes cell death which bears the morphological hallmarks of apoptosis,
      this occurs even in the present of survival promoting NGF and is concomitant with
      new virus production. Using the TUNEL (transferase dUTP nick end labelling)
      technique we show that SFV-induced apoptosis involves DNA fragmentation and
      requires caspase (CED-3/ICE cysteine protease) activation, as does apoptosis
      induced by NGF-deprivation. Extensive areas of apoptosis, as defined using a
      combination of ultrastructural analysis and TUNEL occur in infected neonatal
      mouse brains. The novel evidence that infection of primary neurons with SFV
      induces apoptosis with activation of one or more caspases defines a system for
      the further anlaysis of apoptosis regulation in physiologically relevant neurons.

PMID- 10200446
TI  - Aberrant death in dark chondrocytes of the avian growth plate.
AB  - Growth plate chondrocytes of embryonic chick femurs were examined by electron
      microscopy, cytophotometry and autoradiography. Apart from the well-described
      'light' chondrocyte, a different 'dark' type of chondrocyte was present,
      comprising 10 - 35% of the cell population. They were found at all stages of
      chondrocyte differentiation and in all ages of the femurs studied. Well developed
      rough endoplasmatic reticulum and Golgi complex, many secretory vesicles,
      energetically active mitochondria and a lot of glycogen, indicating high activity
      of the cytoplasm, were combined with low RNA synthesis, gentle margination and
      scattered compaction of the chromatin. DNA cytometry revealed that most of dark
      cells were diploid, but 15 - 30% were tetraploid, with the absence of an S-phase.
      Substantial loss of DNA was found in about 10% of dark chondrocytes. The TUNEL
      reaction demonstrated a limited number of DNA strand breaks. Advanced dark cells
      possessed the nuclear features of both apoptosis and necrosis. Besides
      chromomeric-chromonemic compaction, a chromatin arrangement similar to that of
      prometaphase and metaphase, as well as amitotic nuclear segregation, all of them
      degenerative, were found. Our interpretation is that the dark chondrocytes
      undergo an aberrant type of cell death which may be combined with aberrant cell
      cycle. Cell death of dark chondrocytes is preceded by a pre-mortal burst of
      secretion.

PMID- 10200447
TI  - Analysis of apoptosis and expression of bcl-2 gene family members in the human
      and baboon ovary.
AB  - Recent data support a role for apoptosis, under tight regulatory control by bcl
      2, oxidative stress response, tumor suppressor, and CASP gene family members, in
      mediating granulosa cell demise during follicular atresia in the rodent and avian
      ovary. Herein we evaluated the occurrence of apoptosis in the human and baboon
      ovary relative to follicular health status, and analyzed expression of several
      cell death genes in these tissues. In situlocalization of DNA strand breaks in
      fixed human and baboon ovarian tissue sections indicated that apoptosis was
      essentially restricted to granulosa cells of atretic antral follicles.
      Biochemical analysis of DNA oligonucleosomes in individual follicles isolated
      from baboon ovaries during the ovulatory phase revealed the presence of apoptotic
      DNA fragments in subordinate but not dominant follicles, thus substantiating the
      in situ labeling studies. Messenger RNA transcripts encoded by the bax death
      susceptibility gene, the bcl-xlong survival gene, the bcl-xshort pro-apoptosis
      gene, the p53 tumor suppressor gene, and two members of the CASP gene family
      (CASP-2/Ich-1, CASP-3/CPP32), were detected by Northern blot analysis of total
      RNA prepared either from human ovaries or from Percoll-purified granulosa-lutein
      cells obtained from patients undergoing assisted reproductive technologies.
      Lastly, immunohistochemical localization of the BAX death-susceptibility protein
      in the human ovary revealed abundant expression in granulosa cells of early
      atretic follicles, whereas BAX protein was extremely low or non-detectable in
      healthy or grossly-atretic follicles. We conclude that apoptosis occurs during,
      and is probably responsible for, folicular atresia in the human and baboon ovary.
      Moreover, apoptosis in the human ovary is likely controlled by altered expression
      of the same cohort of cell death regulatory factors recently implicated as
      primary determinants of apoptosis induction or suppression in the rodent ovary.

PMID- 10200448
TI  - Regulation of the apoptotic response to radiation damage in B cell development.
AB  - B lymphocyte precursor cells are ultrasensitive to DNA damage induced by
      irradiation and drugs and die by apoptosis at very low levels of exposure.
      Previous studies have shown that this high level sensitivity is p53-dependent,
      associated with very low level expression of Bcl-2 protein and can be reversed by
      expression of a bcl-2 transgene. We show here that transition from the pro-B to
      pre-B and then mature B cell stages of murine lymphopoiesis is accompanied by
      changes in proliferating cells in sensitivity to X-irradiation induced apoptosis
      and that this is paralleled by variation in the ratio of anti-(Bcl-2/Bcl-chiL) to
      pro-(Bax) apoptotic proteins. These are however not fixed or invariant features
      of developmental stage as they can be modulated by interactions via adhesive
      interactions with stromal cells, stromal proteins and growth factors. We
      interpret these data in the context of the stringent developmental regulation of
      clonal lymphopoiesis and the contingency programming of cells that have extensive
      proliferative potential with a very low threshold for apoptosis following DNA
      damage.

PMID- 10200449
TI  - Wild-type function of the p53 tumor suppressor protein is not required for
      apoptosis of mouse hepatoma cells.
AB  - The role of the tumor suppressor protein p53 in apoptosis of mouse hepatoma cells
      was studied. Different lines were used which were either p53 wild-type or carried
      various types of heterozygous or homozygous p53 mutations. The presence of
      mutations was demonstrated to correlate with a lack in transactivating activity
      of p53. While UV-light effectively produced apoptosis in cells of all lines,
      irrespective of their p53 mutational status, gamma-irradiation induced the
      formation of micronuclei but failed to induce apoptosis. Both UV- and gamma
      irradiation led to nuclear accumulation and increases in p53 protein in p53 wild
      type cells. Similarly, no significant differences in apoptotic response between
      p53 wild-type and p53 mutated cells were seen with other apoptotic stimuli like
      CD95/APO-1/Fas or TNFalpha. These data suggest that wild-type p53 is not required
      for induction of apoptosis in mouse hepatoma cells which may explain the apparent
      lack of p53 mutations in mouse liver tumors.

PMID- 10200450
TI  - Egr-1 inhibits apoptosis during the UV response: correlation of cell survival
      with Egr-1 phosphorylation.
AB  - UV irradiation of normal or immortalized cells induces a rapid increase in the
      expression of several transcription factors and is thought to serve a protective
      function. The human fibrosarcoma cell line, HT1080 clone H4, expresses almost
      undetectable levels of Egr-1 and does not respond to UV-C irradiation by the
      induction of Egr-1. The H4 cells are hypersensitive to UV which induces apoptosis
      and reduces clonogenicity. The introduction of exogenous Egr-1 into H4 (H4E9 and
      H4E4 cell-lines) confers protection from UV damage as measured by a number of
      assays. In both NIH3T3 (with inducible Egr-1) and H4E9 (constitutive Egr-1)
      cells, UV irradiation gave enhanced transactivation of Egr-1 reporters that
      correlated with phosphorylated Egr-1. Studies using inhibitors indicated that
      protein kinase-C and tyrosine kinases are involved in the anti-apoptotic effects
      of Egr-1 after UV damage. This is the first description of a biological effect of
      phosphorylated Egr-1.

PMID- 10200451
TI  - Commitment to cell death measured by loss of clonogenicity is separable from the
      appearance of apoptotic markers.
AB  - Kinetic analysis of dexamethasone-induced apoptosis in the human lymphoblastoid
      cell line CCRF CEM C7A has revealed a point when cells, morphologically
      indistinguishable from untreated cells, have irreversibly engaged a program
      leading to death, measured by a loss of clonogenicity. Since all cells that fail
      to clone eventually died through apoptosis, measurements of clonogenicity in this
      system provide an accurate measure of commitment to apoptotic death. Inhibition
      of caspases by peptide inhibitors blocked proteolysis of endogenous substrates
      and reduced nuclear condensation yet did not alter either dexamethasone-induced
      changes in clonogenicity or mitochondrial membrane potential. In contrast to the
      results with caspase inhibitors, expression of BCL-2 in CCRF CEM C7A cells proved
      sufficient to block all changes associated with apoptosis, including loss of both
      clonogenicity and changes in mitochondrial membrane potential. These results
      demonstrate that commitment to cell death can precede the key biochemical or
      morphological features of apoptosis by several hours and indicate that separate
      regulators govern cellular commitment to clonogenic death and the subsequent
      execution phase characterised as apoptosis.

PMID- 10200452
TI  - Differentially expressed genes in C6.9 glioma cells during vitamin D-induced cell
      death program.
AB  - C6.9 rat glioma cells undergo a cell death program when exposed to 1, 25
      dihydroxyvitamin D3 (1,25-D3). As a global analytical approach, we have
      investigated gene expression in C6.9 engaged in this cell death program using
      differential screening of a rat brain cDNA library with probes derived from
      control and 1,25-D3-treated cells. Using this methodology we report the isolation
      of 61 differentially expressed cDNAs. Forty-seven cDNAs correspond to genes
      already characterized in rat cells or tissues. Seven cDNAs are homologous to
      yeast, mouse or human genes and seven are not related to known genes. Some of the
      characterized genes have been reported to be differentially expressed following
      induction of programmed cell death. These include PMP22/gas3, MGP and beta
      tubulin. For the first time, we also show a cell death program induced up
      regulation of the c-myc associated primary response gene CRP, and of the
      proteasome RN3 subunit and TCTP/mortalin genes. Another interesting feature of
      this 1,25-D3 induced-cell death program is the down-regulated expression of
      transcripts for the microtubule motor dynein heavy chain/MAP 1C and of the
      calcium-binding S100beta protein. Finally 15 upregulated cDNAs encode ribosomal
      proteins suggesting a possible involvement of the translational apparatus in this
      cell program. Alternatively, these ribosomal protein genes could be up-regulated
      in response to altered rates of cellular metabolism, as has been demonstrated for
      most of the other isolated genes which encode proteins involved in metabolic
      pathways. Thus, this study presents to our knowledge the first characterization
      of genes which are differentially expressed during a cell death program induced
      by 1, 25-D3. Therefore, this data provides new information on the fundamental
      mechanisms which participate in the antineoplastic effects of 1,25-D3 and on the
      machinery of a cell death program in a glioma cell line.

PMID- 10200453
TI  - A transgenic mouse model for the study of apoptosis during limb development.

PMID- 10200456
TI  - Apoptosis and the cell cycle: the p53 connection.

PMID- 10200457
TI  - pRb and the cdks in apoptosis and the cell cycle.
AB  - Apoptosis is a fundamental biological process present in metazoan cells. Linking
      apoptosis to the cell cycle machinery provides a mechanism to maintain proper
      control of cell proliferation in a multicellular organism. pRb and the cyclin
      dependent kinases may have dual roles as integral components of the cell cycle
      and regulators of apoptosis. In many instances manipulation of the cell cycle
      through these molecules can induce or inhibit apoptosis. Recent studies also
      identify pRb as a substrate for an apoptotic protease; however, other cell cycle
      components are not known substrates. While it is clear that many common molecules
      can affect cell proliferation and cell death, the universality of any one cell
      cycle molecule in apoptosis has yet to be determined.

PMID- 10200458
TI  - p53 mediates apoptosis induced by c-Myc activation in hypoxic or gamma irradiated
      fibroblasts.
AB  - Deregulated c-Myc expression leads to a cellular state where proliferation and
      apoptosis are equally favored depending on the cellular microenvironment. Since
      the apoptotic sensitivity of many cells is influenced by the status of the p53
      tumor suppressor gene, we investigated whether the induction of apoptosis by DNA
      damage or non-genotoxic stress are also influenced by the p53 status of cells
      with altered c-Myc activity. Rat-1 fibroblasts expressing a conditional c-Myc
      allele (c-MycER), were transfected to express an antisense RNA complimentary to
      p53 mRNA. Expression of antisense p53 RNA decreased p53 protein levels and
      delayed p53 accumulation following c-Myc activation. Under hypoxic or low serum
      conditions, cells expressing antisense p53 were substantially more resistant to c
      Myc-induced apoptosis than were control cells. c-Myc activation also sensitized
      Rat-1 cells to radiation-induced apoptosis. Rat-1 cells expressing antisense p53
      RNA were more resistant to apoptosis induced by the combined effects of c-Myc
      activation and gamma irradiation. In a similar manner, apoptosis induced by c-Myc
      in serum starved, hypoxic or gamma irradiated fibroblasts was also inhibited by
      Bcl-2. These data indicate that p53 is involved in c-Myc-mediated apoptosis under
      a variety of stresses which may influence tumor growth, evolution and response to
      therapy.

PMID- 10200459
TI  - Phenotypic alterations of small cell lung carcinoma induced by different levels
      of wild-type p53 expression.
AB  - p53 induces both growth arrest and apoptosis in cancer cells. To clarify whether
      the level of p53 expression determines the response of small cell lung carcinoma
      (SCLC) cells, we assessed the effect of various p53 levels on a p53-null SCLC
      cell line, N417, using a tetracycline (Tc)-regulated inducible p53 expression
      system. Apoptosis was induced in SCLC cells with high p53 expression. Although
      low levels of p53 induced G1 arrest accompanied by p21 expression, cells with G1
      arrest seemed to undergo apoptosis after further cultivation. Expression of
      exogenous p21 induced G1 arrest but not apoptosis in SCLC cells, suggesting that
      p53-mediated G1 arrest was induced through p21 expression. Moreover, high level
      of p53 expression down-regulated Bcl-2 expression in SCLC cells, while Bax was
      consistently expressed irrespective to the level of p53 expression. These results
      suggest that p53-mediated apoptosis and G1 arrest depend on level of p53
      expression in SCLC cells and that the relative dominancy of Bax to Bcl-2 is
      involved in the induction of apoptosis by high level of p53 expression.

PMID- 10200460
TI  - High frequency of persistent hyperplastic primary vitreous and cataracts in p53
      deficient mice.
AB  - In order to investigate whether the p53 gene product plays a role in normal eye
      development, age matched p53-deficient mice and wild-type controls were
      sacrificed from day 2 to day 21 after birth. Eyes were paraffin-embedded and
      sectioned. Serial sections were taken at the level of the tunica vasculosa lentis
      and the hyaloid artery. The terminal dUTP nick-end labelling technique (TUNEL)
      was used to detect the number of cells displaying DNA fragmentation within these
      structures. Eyes were also prepared for scanning electron microscopy and resin
      embedded for semi-thin sections. Adult wild-type mice and p53-deficient mice were
      examined ophthalmoscopically in vivo. Ophthalmoscopical examination of mice
      completely deficient in p53 revealed them to be normal except for the persistence
      of the hyaloid vasculature, a structure that normally regresses during eye
      development. In adult animals there was also a high frequency of cataracts. Using
      morphological assessment and TUNEL we could show that in normal mice, regression
      of the primary vitreous, which includes the hyaloid artery, the vasa hyaloidea
      propria as well as the tunica vasculosa lentis, occurs via apoptotic cell death
      within 5 - 6 weeks after birth. The number of TUNEL-positive cells within these
      structures was significantly reduced in the p53-deficient mice in which parts of
      the hyaloid vasculature persisted and developed into a fibro-vascular retrolental
      plaque analogous to persistent hyperplastic primary vitreous (PHPV) described in
      humans. As in humans, PHPV in mice resulted in the development of cataracts. We
      have identified a role for p53-dependent apoptosis in the regression of the
      hyaloid vasculature and tunica vasculosa lentis. Our results provide further
      evidence for the importance of p53 in normal development and provide the first
      detailed evidence of its role in postnatal development in remodelling the
      developing eye.

PMID- 10200461
TI  - The C-D interhelical domain of the serpin plasminogen activator inhibitor-type 2
      is required for protection from TNF-alpha induced apoptosis.
AB  - The serine proteinase inhibitor (serpin), plasminogen activator inhibitor type 2
      (PAI-2), has been reported to inhibit tumor necrosis factor-alpha (TNF) induced
      apoptosis. In order to begin to understand the molecular basis for this
      protection, we have investigated the importance of a structural domain within the
      PAI-2 molecule, the C-D interhelical region, in mediating the protective effect.
      The C-D interhelical region is a 33 amino acid insertion which is unique among
      serpins and has been implicated in transglutaminase catalyzed cross-linking of
      PAI-2 to cell membranes. We have constructed a mutant of PAI-2 wherein 23 amino
      acids are deleted from the C-D interhelical region generating a structure
      predicted to be homologous to the closely related, but non-inhibitory serpin,
      chicken ovalbumin. The PAI-2Delta65/87 deletion mutant retained inhibitory
      activity against its known serine proteinase target, urokinase-type plasminogen
      activator (uPA); however expression of this mutant in HeLa cells failed to
      protect from TNF-induced apoptosis. Analyses of the cellular distribution of PAI
      2 showed that intracellular PAI-2, and not secreted or cell-surface PAI-2, was
      likely responsible for the observed protection from TNF-induced apoptosis. No
      evidence was found for specific cross-linking of PAI-2 to the plasma membrane in
      either control or TNF/cycloheximide treated cells. The data demonstrate that the
      PAI-2 C-D interhelical domain is functionally important in PAI-2 protection from
      TNF induced apoptosis and suggest a novel function for the C-D interhelical
      domain in the protective mechanism.

PMID- 10200462
TI  - Lack of ceramide generation in TF-1 human myeloid leukemic cells resistant to
      ionizing radiation.
AB  - The mechanism(s) by which ionizing radiation (IR) induces cell death is of
      fundamental importance in understanding cell sensitivity and resistance. Here we
      evaluated the response to IR of two subclones of the autonomous human
      erythromyeloblastic cell line TF-1: TF-1-34 (which expresses CD34) and TF-1-33
      (which lacks CD34). In clonogenic assays, TF-1-34 cells were found to be
      relatively less sensitive to IR compared to TF-1-33 cells based on the D0
      determination (3.01 vs 1.56 Gy). Furthermore, after IR at 12 Gy, TF-1-33 cell
      viability decreased by approximately 50% within 24 h, whereas TF-1-34 cell growth
      was unaffected during this time. Gradual loss of TF-1-34 cell viability was
      observed only after 48 h. Morphological and molecular analysis revealed that TF-1
      33 cells died of apoptosis, and TF-1-34 cells of delayed reproductive cell death.
      While IR produced comparable amounts of DNA double strand breaks (DSB) in both
      cell lines, TF-1-34 retained DSB much longer than TF-1-33 suggesting that
      radioresistance and the defective apoptotic response of TF-1-34 cells was not
      related to a higher DNA repair capacity. However, the lack of an apoptotic
      response in TF-1-34 was correlated to the absence of a sphingomyelin (SM)
      ceramide (CER) signaling pathway. Indeed, IR triggered in TF-1-33 cells but not
      in TF-1-34, SM hydrolysis (25% at 12 Gy) and CER generation (>50%) through the
      activation of neutral but not acid sphingomyelinase. Synthetic cell permeate CER
      induced apoptosis in both TF-1-33 and TF-1-34 cells. This study indicates that
      alterations of the SM-CER signaling pathway can significantly influence the cell
      death process as well as the survival of acute myeloid leukemia cells after IR
      exposure.

PMID- 10200463
TI  - Distinct cleavage products of nuclear proteins in apoptosis and necrosis revealed
      by autoantibody probes.
AB  - A central mechanism in apoptosis is the activation of proteases of the caspase
      (cysteine aspartases) family. Protease activation has also been implicated in
      necrosis, but its role in this cell death process and the identity of the
      proteases involved and their substrates, are unknown. Using human autoantibodies
      to well characterized cellular proteins as detecting probes in immunoblotting, we
      observed that a defined and somewhat similar set of nuclear proteins, including
      poly (ADP-ribose) polymerase (PARP) and DNA topoisomerase I (Topo I), were
      selectively cleaved during both apoptosis and necrosis of cultured cells induced
      by various stimuli. The resulting cleavage products were distinctively different
      in the two cell death pathways. In contrast to apoptosis, the cleavages of PARP
      and Topo I during necrosis were not blocked by the caspase inhibitor
      benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (zVAD-fmk). These findings
      suggest that different proteases act in apoptosis and necrosis, and that although
      both cell death processes result in selective cleavage of almost identical
      cellular proteins, they can be distinguished immunochemically on the basis of
      their cleavage products.

PMID- 10200464
TI  - Cytolytic P2X purinoceptors.
AB  - Anecdoctal evidence accumulated over almost 20 years has shown that many
      different cell types are killed by sustained exposure to high concentrations of
      extracellular ATP. The plasma membrane receptors involved have been
      pharmacologically characterized and cloned during the last 3 years, and named
      purinergic P2X. P2X receptors share an intriguing structural relatedness with
      Caenorhabditis elegans degenerins and mammalian amiloride-sensitive Na channels
      (ENaCs). Depending on the ATP dose, length of stimulation and receptor subtype,
      P2X receptor stimulation may cause necrosis or apoptosis. The intracellular
      pathways activated are poorly known, but the perturbation in intracellular ion
      homeostasis clearly plays a major role. ICE proteases (caspases) are also
      triggered, nonetheless their activation is not requested for ATP-dependent cell
      death. The physiological meaning of P2X receptor-dependent cytotoxicity is not
      understood, but an involvement in immune-mediated reactions is postulated.

PMID- 10200465
TI  - Sensitivity of S49.1 cells to anti-CD95 (Fas/Apo-1)-induced apoptosis: effects of
      CD95, Bcl-2 or Bcl-x transduction.
AB  - T lymphocytes have variable sensitivity to anti-CD95 which does not correlate
      closely with the level of CD95 expressed. To investigate this phenomenon, we
      screened murine T lymphocyte cultures for their sensitivity to anti-CD95.
      Subclones of the S49.1 cells showed widely variable sensitivity to anti-CD95 but
      similar levels of CD95. The resistant clones became sensitive after treatment
      with actinomycin D suggesting that they expressed resistance protein(s) with a
      high turnover relative to the CD95 apoptosis induction machinery. Our data
      suggest that the resistance protein(s) are not Bcl-2, Bcl-x, Fap-1 or Bag-1.
      Forced, increased expression of CD95 made most of the resistant cells more
      sensitive, but some remained resistant suggesting that the expression of the
      resistant protein(s) is heterogeneous and that increased CD95 levels does not
      always overcome the resistance.

PMID- 10200466
TI  - The adenomatous polyposis coli protein and retinoblastoma protein are cleaved
      early in apoptosis and are potential substrates for caspases.
AB  - Apoptosis in human monocytic THP.1 tumour cells, induced by diverse stimuli, was
      accompanied by proteolytic cleavage of the adenomatous polyposis coli gene
      product (APC) and by sequential cleavage of the retinoblastoma susceptibility
      gene product (Rb). Cleavage of poly(ADP-ribose) polymerase (PARP), APC and the
      initial cleavage of Rb at the carboxy terminal region all occurred at a similar
      time, early in the apoptotic process. Subsequently, Rb underwent a secondary
      cleavage to 43 kDa and 30 kDa protein fragments. Two caspase inhibitors,
      benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethyl ketone (Z-VAD.FMK) and acetyl
      Tyr-Val-Ala-Asp chloromethyl ketone (YVAD.CMK), had markedly different effects on
      the induction of apoptosis. Z-VAD.FMK inhibited the primary and secondary
      cleavage of Rb, cleavage of APC and PARP, and apoptosis assessed by flow
      cytometry. In marked contrast, YVAD.CMK inhibited cleavage of APC and the
      secondary cleavage of Rb to the 43 kDa and 30 kDa protein fragments but did not
      inhibit the primary carboxy terminal cleavage of Rb, PARP proteolysis or
      apoptosis assessed by flow cytometry. These results suggest that different
      caspases are responsible for the cleavage of different substrates at different
      stages during the apoptotic process and that a caspase may either cleave APC
      directly or may be involved in the pathway leading to APC proteolysis. This is
      the first report suggesting that a cytoplasmic tumour suppressor gene (APC) may
      be cleaved by a caspase during apoptosis.

PMID- 10200467
TI  - Induction of apoptosis by valinomycin: mitochondrial permeability transition
      causes intracellular acidification.
AB  - In order to determine whether disruption of mitochondrial function could trigger
      apoptosis in murine haematopoietic cells, we used the potassium ionophore
      valinomycin. Valinomycin induces apoptosis in the murine pre-B cell line BAF3,
      which cannot be inhibited by interleukin-3 addition or Bcl-2 over-expression.
      Valinomycin triggers rapid loss of mitochondrial membrane potential. This
      precedes cytoplasmic acidification, which leads to cysteine-active-site protease
      activation, DNA fragmentation and cell death. Bongkrekic acid, an inhibitor of
      the mitochondrial permeability transition, prevents acidification and subsequent
      induction of apoptosis by valinomycin.

PMID- 10200468
TI  - Anti-CD95 (APO-1/Fas) autoantibodies and T cell depletion in human
      immunodeficiency virus type 1 (HIV-1)-infected children.
AB  - Advanced stages of HIV-1-infection are characterized by progressive CD4+ T cell
      depletion. Peripheral T cells from HIV-1+ donors show accelerated apoptosis in
      vitro. The CD95 (APO-1/Fas) receptor/ligand system is involved in this process.
      To further study deregulation of the CD95 system in peripheral T cells during HIV
      1-infection, we measured CD95-expression on CD4+ and CD8+ T cells together with
      serum levels of soluble CD95 (sCD95) and anti-CD95 autoantibodies in HIV-1+
      children and healthy controls. Anti-CD95 levels in HIV-1+ children were
      significantly elevated when compared to uninfected controls, whereas serum levels
      of sCD95 were not different. In HIV-1+ children, CD95-expression on CD4+ and CD8+
      T cells increased with age. A strong correlation between depletion of CD4+ cells
      in vivo and increase in CD95-expression on CD4+ T cells was observed. In
      contrast, such a correlation was not found for CD8+ T cells. A negative
      correlation between anti-CD95 autoantibody levels and CD4+ T cell counts, that
      was predicted by multiple linear regression analysis of pooled data, was found in
      individual patients observed longitudinally by repeated measurements. Since anti
      CD95 autoantibodies isolated from HIV-infected adults have previously been shown
      to induce apoptosis of sensitive target cells in vitro, we speculate that the
      interaction of these antibodies with CD95-positive and CD95-sensitive T cells in
      vivo might be involved in progressive T cell loss during HIV-1-infection.

PMID- 10200469
TI  - Selective killing of CD8+ cells with a 'memory' phenotype (CD62Llo) by the N
      acetyl-D-galactosamine-specific lectin from Viscum album L.
AB  - As reported previously by our group, among the toxic proteins from Viscum album
      L. only the mistletoe lectins (MLs) induce the apoptotic killing pathway in human
      lymphocytes. Although one may expect a homogenous distribution of carbohydrate
      domains on cell surface receptors for the carbohydrate binding B chains of the
      toxic protein, the sensitivity of cells to these B chains obviously differ. Here
      we report a selective killing of CD8+ CD62Llo cells from healthy individuals by
      the galNAc-specific ML III (and RCA60, which binds to gal and galNAc), while the
      gal-specific ML I was less effective. This selective killing is not sufficiently
      explained by protein synthesis inhibition alone, since this subset was not
      affected by other ribosome inhibiting proteins such as the lectin from Ricinus
      communis (RCA120), lectin from Abrus precatorus (APA), abrin A, and inhibitors of
      RNA, DNA and/or protein synthesis such as actinomycin D, mitomycin C, and
      cycloheximide. We conclude that CD8+ cells with 'memory' phenotype (CD62Llo) are
      more sensitive to the ML III-mediated killing than their CD8+ CD62Lhi
      counterparts, CD4+ T cells, and CD19+ B cells. These cells probably express a
      distinct receptor with galNAc domains that is missing or not active on CD8+ cells
      with a 'naive' phenotype.

PMID- 10200470
TI  - Caspases are the main executioners of Fas-mediated apoptosis, irrespective of the
      ceramide signalling pathway.
AB  - Tumor necrosis factor alpha (TNF) or cytotoxic anti-Fas antibodies lead to the
      activation of apoptotic proteases (caspases) and to sphingomyelinase-mediated
      ceramide generation. Caspases and ceramide are both known to induce apoptosis on
      its own, but their relative contribution to Fas- and TNF-induced cell death is
      not well established. We report here that rapid apoptosis induced by TNF in U937
      cells or anti-Fas in Jurkat cells, in the presence of cycloheximide, induced only
      a very low increase (<20%) in the cell ceramide content. Neither treatment with
      inhibitors of sphingomyelinases nor incubation of cells with fumonisin B1, which
      inhibits de novo ceramide synthesis, prevented TNF and Fas-mediated apoptosis.
      Increasing or depleting the cell ceramide content by prolonged culture in the
      presence of monensin or fumonisin B1, respectively, did not prevent TNF and Fas
      mediated apoptosis. Treatment of cells with sphingomyelinase inhibitors did not
      affect to the activation of CPP32 (caspase-3) induced by TNF or anti-Fas
      antibodies. Chromatin condensation and fragmentation in cells treated with anti
      Fas or TNF was abrogated by peptide inhibitors of caspases, which also inhibited
      Fas-, but not TNF-induced cell death. These results indicate that while ceramide
      does not seem to act as a critical mediator of TNF and Fas-induced apoptosis, it
      is generated as a consequence of CPP32 activation and could contribute to the
      spread of the intracellular death signal.

PMID- 10200471
TI  - Analysis of nuclear degradation during lens cell differentiation.
AB  - Lens cells demonstrate a terminal differentiation process with loss of their
      organelles including nuclei. Chromatin disappearance is characterised by the same
      changes as most apoptotic cells, i.e. condensation of chromatin and cleavage into
      high molecular weight fragments and oligonucleosomes. The endo-deoxyribonucleases
      (bicationic (Ca2+, Mg2+), mono-cationic (Ca2+ or Mg2+) and acidic non-cationic
      dependent nucleases) are present in lens fibre cells. Our results suggest that
      the acidic non-cationic nuclease (DNase II) plays a major role in chromatin
      cleavage. This nuclease, known to be lysosomal, is found in lens fibre nuclei and
      only an antibody directed against DNase II inhibits the acidic DNA cleavage of
      lens fibre nuclei. In addition, there must be another DNase implicated in the
      process which is not DNase I but appears to be a Ca2+, Mg2+ dependent molecule.
      Regulation of these DNase activities may be accomplished by the effect of post
      translational modifications, acidic pH, mitochondrial release molecules, growth
      factors or oncogenes. Finally, fibre cells lose organelles without cytoplasmic
      elimination. The survival of these differentiated cells might be due to the
      action of survival factors such as FGF 1.

PMID- 10200472
TI  - Argos induces programmed cell death in the developing Drosophila eye by
      inhibition of the Ras pathway.
AB  - We studied the role of Ras signaling in the regulation of cell death during
      Drosophila eye development. Overexpression of Argos, a diffusible inhibitor of
      the EGF receptor and Ras signaling, caused excessive cell death in developing
      eyes at pupal stages. The Argos-induced cell death was suppressed by coexpression
      of the anti-apoptotic genes p35, diap1, or diap2 in the eye as well as by the
      Df(3L)H99 chromosomal deletion that lacks three apoptosis-inducing genes, reaper,
      head involution defective (hid) and grim. Transient misexpression of the
      activated Ras1 protein (Ras1V12) later in pupal development suppressed the Argos
      induced cell death. Thus, Argos-induced cell death seemed to have resulted from
      the suppression of the anti-apoptotic function of Ras. Conversely, cell death
      induced by overexpression of Hid was suppressed by gain-of-function mutations of
      the genes coding for MEK and ERK. These results support the idea that Ras
      signaling functions in two distinct processes during eye development, first
      triggering the recruitment of cells and later negatively regulating cell death.

PMID- 10200473
TI  - Cell death attenuation by 'Usurpin', a mammalian DED-caspase homologue that
      precludes caspase-8 recruitment and activation by the CD-95 (Fas, APO-1) receptor
      complex.
AB  - Apoptotic cell suicide initiated by ligation of CD95 (Fas/APO-1) occurs through
      recruitment, oligomerization and autocatalytic activation of the cysteine
      protease, caspase-8 (MACH, FLICE, Mch5). An endogenous mammalian regulator of
      this process, named Usurpin, has been identified (aliases for Usurpin include
      CASH, Casper, CLARP, FLAME-1, FLIP, I-FLICE and MRIT). This protein is
      ubiquitously expressed and exists as at least three isoforms arising by
      alternative mRNA splicing. The Usurpin gene is comprised of 13 exons and is
      clustered within approximately 200 Kb with the caspase-8 and -10 genes on human
      chromosome 2q33-34. The Usurpin polypeptide has features in common with pro
      caspase-8 and -10, including tandem 'death effector domains' on the N-terminus of
      a large subunit/small subunit caspase-like domain, but it lacks key residues that
      are necessary for caspase proteolytic activity, including the His and Cys which
      form the catalytic substrates diad, and residues that stabilize the P1 aspartic
      acid in substrates. Retro-mutation of these residues to functional caspase
      counterparts failed to restore proteolytic activity, indicating that other
      determinants also ensure the absence of catalytic potential. Usurpin
      heterodimerized with pro-caspase-8 in vitro and precluded pro-caspase-8
      recruitment by the FADD/MORT1 adapter protein. Cell death induced by CD95
      (Fas/APO-1) ligation was attenuated in cells transfected with Usurpin. In vivo, a
      Usurpin deficit was found in cardiac infarcts where TUNEL-positive myocytes and
      active caspase-3 expression were prominent following ischemia/reperfusion injury.
      In contrast, abundant Usurpin expression (and a caspase-3 deficit) occurred in
      surrounding unaffected cardiac tissue, suggesting reciprocal regulation of these
      pro- and anti-apoptotic molecules in vivo. Usurpin thus appears to be an
      endogenous modulator of apoptosis sensitivity in mammalian cells, including the
      susceptibility of cardiac myocytes to apoptotic death following ischemia/
      reperfusion injury.

PMID- 10200474
TI  - Wortmannin enhances activation of CPP32 (Caspase-3) induced by TNF or anti-Fas.
AB  - CPP32/apopain (Caspase-3), a protease of the Ced-3/ICE family, is a central
      mediator in the apoptosis induced by TNF or anti-Fas. In this study we
      demonstrate that wortmannin, an inhibitor of PI-3K, enhances the activation of
      CPP32 (Caspase-3) and DNA fragmentation in TNF-treated U937 cells and anti-Fas
      treated Jurkat cells. Caspase-3-like activity, Ac-DEVD-MCA cleavage activity, is
      enhanced by wortmannin in the range of the concentration (1 - 100 nM)
      specifically inhibiting PI-3K. LY294002, another PI-3K inhibitor, also enhances
      Caspase-3-like activity, but inhibitors for myosin light chain kinase and
      calmodulin dependent kinase do not have any effect on the Caspase-3-like
      activity. Wortmannin (1 - 100 nM) enhances the processing of Caspase-3 (32K) into
      active form (17K) in TNF- or anti-Fas-treated cells, but not in untreated cells.
      These observations suggest that inhibition of PI-3K induces the activation of
      processing enzyme of Caspase-3 or increases the susceptibility of Caspase-3 to
      the processing enzyme. PI-3K seems to protect the cells from apoptosis by
      suppressing the activation of Caspase-3.

PMID- 10200476
TI  - Sodium butyrate induces apoptosis and accumulation of ubiquitinated proteins in
      human breast carcinoma cells.
AB  - To investigate the possible relationship between apoptosis and the ubiquitin
      pathway we examined the patterns of ubiquitinated proteins in the human breast
      carcinoma MCF-7 cell line following induction of apoptotic death by sodium
      butyrate. Apoptosis in these cells was associated with internucleosomal DNA
      fragmentation and proteolytic cleavage of poly(ADP-ribose) polymerase. By dual in
      situ antiubiquitin immunofluorescence and chromatin DNA staining, we demonstrated
      that ubiquitin fluorescence was increased specifically in cells that underwent
      sodium butyrate-mediated apoptosis. The extent of ubiquitin incorporation into
      protein conjugates was examined in both adherent (not yet apoptotic) and floating
      (apoptotic) cell populations. We found that apoptotic cells exhibited enhanced
      intensity of ubiquitin-immunoreactive conjugates, whereas adherent cells did not.
      In addition, two-dimensional immunoblot analysis of proteins from apoptotic cells
      identified a set of isomeric ubiquitinated conjugates located at a pI range of 4.
      2 - 4.6 and a Mr approximately of 30 kDa. These data indicate that the ubiquitin
      pathway may play a role in the sodium butyrate-induced apoptotic program in
      breast carcinoma cells.

PMID- 10200475
TI  - Anti-apoptotic oncogenes prevent caspase-dependent and independent commitment for
      cell death.
AB  - Apoptosis is a morphologically defined type of cell death associated with the
      activation of certain proteases belonging to the ICE/CED-3 family, known as
      caspases. Resistance to apoptosis has been implicated as one of the mechanisms
      that participates in oncogenesis. We found that the broad-spectrum peptide
      inhibitor of the caspases, zVAD-fmk, interferes in a dose-dependent way with all
      the morphological and biochemical changes associated with apoptosis induced by
      anti-CD95 mAb, staurosporine, VP-16 and Act-D. However, with the exception of
      anti-CD95-triggered apoptosis, the insulted cells lost their clonogenic
      potential, even when pre-treated with a high dose of zVAD-fmk. Under these
      circumstances, the dying cells displayed no signs of apoptosis, including
      activation of caspases, externalization of phosphatidylserine, nuclear
      condensation, or DNA fragmentation. Instead, this cell death was characterized by
      cytoplasmic and nuclear vacuolization followed by the loss of plasma membrane
      integrity. Thus, preventing the onset of apoptosis by blocking caspase activity
      did not rescue cells from dying in response to drugs such as staurosporine, VP-16
      and Act-D. In comparison, ectopic expression of anti-apoptotic oncogenes such as
      bcl-2 and bcr-abl not only inhibited apoptosis but also preserved the clonogenic
      potential of the cells. Therefore, oncogenesis is promoted not by simply
      interfering with caspase-mediated apoptosis, but by preventing an upstream event
      which we define as the commitment point for cell death.

PMID- 10200477
TI  - The role of 2'-5' oligoadenylate-activated ribonuclease L in apoptosis.
AB  - Apoptosis of viral infected cells appears to be one defense strategy to limit
      viral infection. Interferon can also confer viral resistance by the induction of
      the 2-5A system comprised of 2'-5' oligoadenylate synthetase (OAS), and RNase L.
      Since rRNA is degraded upon activation of RNase L and during apoptosis and since
      both of these processes serve antiviral functions, we examined the role RNase L
      may play in cell death. Inhibition of RNase L activity, by transfection with a
      dominant negative mutant, blocked staurosporine-induced apoptosis of NIH3T3 cells
      and SV40-transformed BALB/c cells. In addition, K562 cell lines expressing
      inactive RNase L were more resistant to apoptosis induced by decreased
      glutathione levels. Hydrogen peroxide-induced death of NIH3T3 cells did not occur
      by apoptosis and was not dependent upon active RNAse L. Apoptosis regulatory
      proteins of the Bcl-2 family did not exhibit altered expression levels in the
      absence of RNase L activity. RNase L is required for certain pathways of cell
      death and may help mediate viral-induced apoptosis.

PMID- 10200478
TI  - Relation of impaired energy metabolism to apoptosis and necrosis following
      transient cerebral hypoxia-ischaemia.
AB  - This study investigated whether both mild and severe hypoxia-ischaemia (HI)
      caused significant numbers of cells to die by apoptosis in the developing brain
      in vivo. Newborn piglets were subjected to transient global HI and the fraction
      of all cells in the cingulate gyrus that were apoptotic or necrotic counted 48 h
      after resuscitation. The mean (S.D.) proportion of apoptotic cells was 11.9%
      (6.7%) (sham operated controls 4.1% (2.7%)), while 11.4% (8.4%) were necrotic
      (controls 0.7% (1.3%)) (P<0.05). Apoptotic and necrotic cell counts were both
      linearly related to the severity of impaired cerebral energy metabolism measured
      by magnetic resonance spectroscopy (P<0.05), as shown by: (1) the decline in the
      ratio of nucleotide triphosphates to the exchangeable phosphate pool during HI;
      (2) the fall in the ratio of phosphocreatine to inorganic phosphate 8 - 48 h
      after HI; and (3) an increased ratio of lactate to total creatine at both these
      times. Thus both apoptosis and necrosis occurred in the cingulate gyrus after
      both severe and mild HI in vivo in proportion to the severity of the insult.

PMID- 10200479
TI  - Departing is such sweet sorrow.

PMID- 10200480
TI  - Apoptosis in Greece.

PMID- 10200481
TI  - Lymphohematopoiesis in health and diseaseedited by Nydia G. Testa, Brian I. Lord,
      T. Michael Dexter.

PMID- 10200482
TI  - Life and death decisions: a biological role for the p75 neurotrophin receptor.

PMID- 10200483
TI  - p75NTR: A study in contrasts.
AB  - The p75 neurotrophin receptor (p75NTR) and trkA, trkB and trkC mediate the
      physiological effects of the neurotrophins. The trk receptors are responsible for
      the stereotypical survival and growth properties of the neurotrophins but
      defining the physiological function of the p75NTR has proven difficult. The
      p75NTR binds each of the neurotrophins with low nanomolar affinity whereas the
      three trk receptors show strong binding preferences for individual neurotrophins;
      in some cell types, p75NTR is the only neurotrophin receptor whereas in others it
      is co-expressed with the trks. The analysis of p75NTR function has been
      complicated by the fact that the predominant physiological role of p75NTR changes
      dramatically depending on cell context. Available data suggests that in cells
      where p75NTR is co-expressed with trk receptors, p75NTR functionally collaborates
      with the trks to either enhance responses to preferred trk ligands, to reduce
      neurotrophin-mediated trk receptor activation resulting from non-preferred
      ligands or to facilitate apoptosis resulting from neurotrophin withdrawal. In
      cells lacking trk expression, p75NTR can act autonomously to activate ligand
      dependent signaling cascades that may in some circumstances result in apoptosis
      but probably not through pathways utilized by its apoptotic brethren in the TNF
      receptor superfamily. Potential mechanisms for each of these functions of p75NTR
      are considered and the physiological implications of this unique signaling system
      are discussed.

PMID- 10200484
TI  - Neurotrophins: the biological paradox of survival factors eliciting apoptosis.
AB  - Neurotrophins are target-derived soluble polypeptides required for neuronal
      survival. Binding of neurotrophins to Trk receptor tyrosine kinases initiate
      signaling cascades that promote cell survival and differentiation. All family
      members bind to another receptor (p75NTR), which belongs to the tumor necrosis
      factor superfamily. Hence, nerve growth factor (NGF) and related trophic factors
      are unique in that two separate receptor types are utilized. Although the
      biological function of p75NTR has been elusive, it has been suggested to mediate
      apoptosis of developing neurons in the absence of Trk receptors. This presents a
      tantalizing paradigm, in which life-death decisions of cells are dependent upon
      the expression and action of two different receptors with distinctive signaling
      mechanisms. In the presence of TrkA receptors, p75 can participate in the
      formation of high affinity binding sites and enhanced NGF responsiveness leading
      to a survival signal. In the absence of TrkA receptors, p75 can generate, in only
      specific cell populations, a death signal. Here we discuss the unique features
      and implications of this unusual signal transduction system.

PMID- 10200485
TI  - p75NTR and the concept of cellular dependence: seeing how the other half die.
AB  - Cells depend on specific stimuli, such as trophic factors, for survival and in
      the absence of such stimuli, undergo apoptosis. How do cells initiate apoptosis
      in response to the withdrawal of trophic factors or other dependent stimuli?
      Recent studies of apoptosis induction by neurotrophin withdrawal argue for a
      novel form of pro-apoptotic signal transduction - 'negative signal transduction' 
      in which the absence of ligand-receptor interaction induces cell death. We have
      found that the prototype for this form of signaling - the common neurotrophin
      receptor, p75NTR - creates a state of cellular dependence (or addiction) on
      neurotrophins, and that this effect requires an 'addiction/dependence domain'
      (ADD) in the intracytoplasmic region of p75NTR. We have recently found other
      receptors that include dependence domains, arguing that dependence receptors, and
      their associated dependence domains, may be involved in a rather general
      mechanism to create cellular states of dependence on trophic factors, cytokines,
      adhesion, electrical activity and other dependent stimuli.

PMID- 10200486
TI  - Bcl-2 family proteins as ion-channels.
AB  - The Bcl-2 protein family function(s) as important regulators of cellular
      decisions to heed or ignore death signals. The three-dimensional structure of the
      Bcl-2 homolog, Bcl-XL, bears a strong resemblance to some pore-forming bacterial
      toxins. This similarity suggested that the Bcl-2 family proteins may also possess
      channel-forming capability. This review summarizes the recent initial studies on
      the in vitro channel activity of Bcl-2, Bcl-XL and Bax and offers some
      speculation as to the physiological role that these channels may play in the cell
      death pathway.

PMID- 10200487
TI  - The growth arrest and downregulation of c-myc transcription induced by ceramide
      are related events dependent on p21 induction, Rb underphosphorylation and E2F
      sequestering.
AB  - Ceramide is an intracellular lipid mediator generated through the sphingomyelin
      cycle in response to several extracellular signals. Ceramide has been shown to
      induce growth inhibition, c-myc downmodulation and apoptosis. In this paper we
      examined the mechanism by which ceramide induces growth suppression and the role
      of the G1-CDK/pRb/E2F pathway in this process. The addition of exogenous, cell
      permeable C2-ceramide to the Hs 27 human diploid fibroblast cell line resulted in
      a dose-dependent induction of the p21WAF1/CIP1/Sdi1 kinase inhibitor with
      reduction of cyclin-D1 associated kinase activity. Furthermore, significant
      dephosphorylation of pRb was observed, with increased association of pRb and the
      E2F transcription factor into a transcriptionally inactive complex. Ceramide was
      also capable of inhibiting the transcriptional activity of a CAT reporter vector
      driven by E2F binding sites containing c-myc promoter transfected into Hs 27
      cells. The requirement of the pRb protein for ceramide-induced c-myc
      downregulation was supported by the failure of ceramide to inhibit promoter
      activity in HeLa cells, in which pRb function is abrogated by the presence of the
      E7 Papilloma virus oncoprotein, and in pRb-deleted SAOS2 AT cells. Ceramide
      induced downregulation of the c-myc promoter was restored in SAOS2 #1 cells in
      which a functional Rb gene was reintroduced. Our studies demonstrate that pRb
      dephosphorylation, induced by ceramide, is at least partly necessary for c-myc
      downregulation, and therefore the CDK-Rb-E2F pathway appears to be a target for
      the ceramide-induced modulation of cell cycle regulated gene transcription.

PMID- 10200488
TI  - Alteration in p53 pathway and defect in apoptosis contribute independently to
      cisplatin-resistance.
AB  - The accumulation of molecular genetic defects selected during the adaptation
      process in the development of cisplatin-resistance was studied using progressive
      cisplatin-resistant variants (L1210/DDP2, L1210/DDP5, L1210/DDP10) derived from a
      murine leukemia cell line (L1210/0). Of these cell lines, only the most resistant
      L1210/DDP10 was cross-resistant to etoposide and deficient in apoptosis induced
      by these two drugs, indicating that resistance to DNA-damaging agents correlates
      with a defect in apoptosis. This defect was tightly associated with the loss of a
      Ca2+/Mg2+-dependent nuclear endonuclease activity present in the less cisplatin
      resistant cells. Evidence is presented that p53-dependent function (a) is lost
      not only in the apoptosis defective L1210/DDP10 cells, but also in the apoptosis
      susceptible L1210/DDP5 cells; (b) is unrelated to drug-induced cell cycle
      perturbations. These results suggest that deficiency in the p53 pathway and
      resistance to DNA-damaging agents due to a defect in apoptosis are independent
      events.

PMID- 10200489
TI  - The RB-related gene Rb2/p130 in neuroblastoma differentiation and in B-myb
      promoter down-regulation.
AB  - The retinoblastoma family of nuclear factors is composed of RB, the prototype of
      the tumour suppressor genes and of the strictly related genes p107 and Rb2/p130.
      The three genes code for proteins, namely pRb, p107 and pRb2/p130, that share
      similar structures and functions. These proteins are expressed, often
      simultaneously, in many cell types and are involved in the regulation of
      proliferation and differentiation. We determined the expression and the
      phosphorylation of the RB family gene products during the DMSO-induced
      differentiation of the N1E-115 murine neuroblastoma cells. In this system,
      pRb2/p130 was strongly up-regulated during mid-late differentiation stages,
      while, on the contrary, pRb and p107 resulted markedly decreased at late stages.
      Differentiating N1E-115 cells also showed a progressive decrease in B-myb levels,
      a proliferation-related protein whose constitutive expression inhibits neuronal
      differentiation. Transfection of each of the RB family genes in these cells was
      able, at different degrees, to induce neuronal differentiation, to inhibit
      [3H]thymidine incorporation and to down-regulate the activity of the B-myb
      promoter.

PMID- 10200490
TI  - Developmental expression patterns of Bcl-2, Bcl-x, Bax, and Bak in teeth.
AB  - The ontogenic profile of expression of four members of the Bcl-2 family (Bcl-2,
      Bcl-x, Bax and Bak) was examined in the mouse by immunohistochemistry using
      paraffin sections. All four members were expressed in changing patterns during
      critical stages of tooth morphogenesis. Expression was detected in epithelial
      cell populations including the dental lamina, internal dental epithelium (IDE;
      differentiating ameloblasts), stratum intermedium and stellate reticulum cells,
      as well as in the condensed dental mesenchyme. The temporo-spatial localization
      of the various members of the Bcl-2 family in dental epithelium and mesenchyme
      showed striking overlapping areas but often their expression patterns differed.
      In general, contemporaneous co-expression of the Bcl-2 and Bax proteins, and of
      the Bcl-x and Bak proteins was noted in various types of cells during the
      developmental process, with the intensity of Bcl-2>Bax and of Bak>Bcl-x.
      Expression was pronounced at sites where interaction between surface ectoderm and
      induced mesenchyme takes place, and at the enamel knot, which is regarded as
      organization/regulating center for tooth development. Around birth, after the
      structural maturation was accomplished, the expression was down-regulated. The
      absence of elevated expression of each of these four members of the Bcl-2 family
      after birth in the teeth suggests that these proteins are relevant during the
      accomplishment of the basic architecture but not once the structure of the tooth
      is established.

PMID- 10200491
TI  - An insertional mutagenesis approach to Dictyostelium cell death.
AB  - Programmed cell death (PCD) in Dictyostelium shows a pattern of ordered
      degeneration similar to that observed in higher eukaryotes but somewhat different
      from the most studied form of PCD, i.e. apoptosis. To contribute to a genetic
      definition of this process, Dictyostelium HMX44A cells have been subjected to
      insertional mutagenesis, followed by selection based on several rounds of
      differentiation/regrowth to recover only cells resistant to death. We describe
      here the approach used, a partial characterization of the first mutant thus
      obtained called C5 showing some dissociation of cell death signs, and, in this
      case where plasmid rescue was not possible, as a first step towards
      identification of the gene at play recovery of genomic flanking sequences via
      genomic recircularization and PCR. This work demonstrates the feasibility of an
      insertional mutagenesis approach to obtain death-resistant mutants in
      Dictyostelium.

PMID- 10200492
TI  - Co-expression of Fas and Fas-ligand on the surface of influenza virus-infected
      cells.
AB  - Influenza virus-infected cultured cells undergo apoptosis after an increment of
      Fas (APO-1/CD95) on the cell surface. By flow cytometry, cell surface Fas-ligand
      was detected in virus-infected cells with a time course similar to that of Fas.
      Moreover, Fas and Fas-ligand were co-expressed in those cells. The mode of
      induction, however, appeared to be distinct for the two proteins. Influenza virus
      infection induced the externalization of phosphatidylserine on the cell surface
      at the early stage of apoptosis, an event that has been observed in cells
      undergoing Fas-mediated apoptosis. In fact, apoptosis of the virus-infected cells
      was inhibited in the presence of an antagonistic anti-Fas-ligand monoclonal
      antibody. These results suggest that influenza virus infection causes augmented
      expression of both Fas and Fas-ligand and apoptosis is induced when the infected
      cells come into contact with each other.

PMID- 10200493
TI  - Comparative effects of Bcl-2 over-expression and ZVAD.FMK treatment on
      dexamethasone and VP16-induced apoptosis in CEM cells.
AB  - It is becoming apparent that caspases are essential mediators of the execution
      phase of apoptosis. A decrease in mitochondrial membrane potential (PsiM) is also
      thought to be an early event in apoptosis. In this study, we compare the effects
      of Bcl-2 over-expression against N-benzyloxycabonyl-Val-Ala-Asp
      fluoromethylketone (ZVAD. FMK)-sensitive caspase blockade on dexamethasone (DEX)
      and etoposide (VP16)-induced apoptosis in CEM T lymphoid cells. We assessed
      changes in nuclear chromatin, cell size, fragmentation, cell membrane
      permeability and PsiM. We found Bcl-2 over-expression and ZVAD.FMK-sensitive
      caspase inhibition were able to prevent chromatin condensation and cellular
      fragmentation. However, ZVAD.FMK was neither able to prevent loss of plasma
      membrane integrity nor PsiM depolarization which occur in both VP16 and DEX
      induced apoptosis. In VP16-induced apoptosis, the increase in cell membrane
      permeability was actually potentiated by caspase inhibition. Interestingly,
      ZVAD.FMK did prevent VP16-induced but not DEX-induced cell shrinkage. These
      results suggest that not all the actions of Bcl-2 can be explained by its ability
      to prevent caspase activation. Rather Bcl-2 must have other targets of action
      which include functions associated with mitochondria.

PMID- 10200494
TI  - Cripto: roles in mammary cell growth, survival, differentiation and
      transformation.
AB  - Cripto-1 (Cr-1) protein, encoded by the teratocarcinoma-derived growth factor
      gene (TDGF-1), is highly correlated with transformation in breast cancer. Eighty
      two percent of breast carcinomas express Cr-1 whereas it is undetected in normal
      human breast tissue. We confirmed and extended findings that Cr-1 protein is
      expressed during the pregnancy and lactating stages of normal murine mammary
      glands but is barely detectable in glands from virgin animals and is undetectable
      in involuted glands. Cr-1 was found to be expressed in CID 9 cells, a line of
      mammary epithelial cells derived from 14.5 day pregnant mice and we have used
      these cells to investigate the roles of this gene. Exogenous mouse Cr-1
      expression from a retroviral vector caused CID 9 cells to grow at an increased
      rate and to increased cell densities compared to parental and control cells. CID
      9 cells overexpressing Cr-1 did not differentiate efficiently. Infection of CID 9
      cells with a Cr-1 antisense vector caused these cells to change in morphology, to
      grow slowly, to undergo apoptosis at a higher rate and to achieve lower
      saturation densities but the cells were still capable of differentiating. We
      concluded that Cr-1 is an autocrine growth factor for normal breast cells, that
      when over-expressed stimulates excessive cell proliferation at the expense of
      differentiation. In transplantation studies, Cr-1 over-expression stimulated the
      growth and survival of mammary cells, but did not stimulate tumorigenesis in
      vivo.

PMID- 10200496
TI  - Back to the future: the role of cytochrome c in cell death.

PMID- 10200495
TI  - Expression of genes that regulate Fas signalling and Fas-mediated apoptosis in
      colon carcinoma cells.
AB  - The expression of genes that regulate Fas-induced apoptosis has been examined in
      10 human cultured colon carcinoma cell lines with defined and varied sensitivity
      to the cytolytic anti-Fas MoAb CH-11. Four lines demonstrated sensitivity to CH
      11 (HT29, GC3/c1, TS-, Thy4), and six were resistant to the induction of
      apoptosis vis Fas. In nine lines expressing Fas, PCR-sequencing indicated that
      the death domain contained wt sequences. Downstream of Fas, expression of
      FADD/MORT1 and FLICE, essential components of the DISC, and negative regulators
      of Fas signalling including sFas, FAP-1 and Bcl-2, showed no correlation between
      levels of expression and sensitivity to Fas-mediated cytotoxicity. However,
      levels of the Fas antigen varied by >1000-fold, and correlated with CH-11
      sensitivity. Following fourfold elevation in Fas expression in HT29 cells treated
      with interferon-gamma, a synergistic effect on Fas-mediated apoptosis was
      obtained when CH-11 and interferon-gamma were combined.

PMID- 10200497
TI  - Aspects of the involvement of interleukin-1 and nitric oxide in the pathogenesis
      of insulin-dependent diabetes mellitus.
AB  - The possible involvement of the cytokine interleukin-1 (IL-1) and nitric oxide
      (NO) in the pathogenesis of insulin-dependent diabetes mellitus (IDDM) is
      reviewed and current and potential therapies are discussed. IDDM is a common
      disorder in the Western world and it is rising in incidence. In IDDM, islet
      infiltrating macrophages produce IL-1 which is cytotoxic specifically to beta
      cells in vitro. IL-1 increases beta-cell formation of NO, ceramide,
      prostaglandins, heat-shock proteins, and activates a protease. Additionally, IL-1
      depresses beta-cell energy production, insulin gene expression and cyclic AMP
      synthesis, and impacts negatively on different parts of the insulin stimulus
      secretion coupling, actions mimicked by NO. Conversely, blocking NO formation
      prevented many of these effects in most reports published. Also, changes in
      cyclic AMP and prostaglandins seem unlikely events in mediating the cytotoxicity
      of IL-1, while the role of ceramide remains less clear. Peptides capable of
      blocking beta-cell IL-1 receptors, and agents blocking NO synthesis may prove
      valuable in preserving beta-cell function in IDDM. Although IDDM causes immense
      morbidity and expense, uniformly effective preventive or beta-cell protective
      therapy is not currently available. If IL-1 is causing beta-cell dysfunction in
      human IDDM through NO production, several processes in the IL-1-NO connection are
      appropriate targets for agents protecting beta-cells from destruction and
      functional inhibition in IDDM.

PMID- 10200498
TI  - A cytosolic factor is required for mitochondrial cytochrome c efflux during
      apoptosis.
AB  - Treatment of HL-60 cells with staurosporine (STS) induced mitochondrial
      cytochrome c efflux into the cytosol, which was followed by caspase-3 activation
      and apoptosis. Consistent with these observations, in vitro experiments
      demonstrated that, except for cytochrome c, the cytosol of HL-60 cells contained
      sufficient amounts of all factors required for caspase-3 activation. In contrast,
      treatment of HCW-2 cells (an apoptotic-resistant HL-60 subclone) with STS failed
      to induce significant amounts of mitochondrial cytochrome c efflux, caspase-3
      activation, and apoptosis. In vitro assays strongly suggested that a lack of
      cytochrome c in the cytosol was the primary limiting factor for caspase-3
      activation in HCW-2 cells. To explore the mechanism which regulates mitochondrial
      cytochrome c efflux, we developed an in vitro assay which showed that cytosolic
      extracts from STS-treated, but not untreated, HL-60 cells contained an activity,
      which we designated 'CIF' (cytochrome c-efflux inducing factor), which rapidly
      induced cytochrome c efflux from HL-60 mitochondria. In contrast, there was no
      detectable CIF activity in STS-treated HCW-2 cells although the mitochondria from
      HCW-2 cells were responsive to the CIF activity from STS-treated HL-60 cells.
      These experiments have identified a novel activity, CIF, which is required for
      cytochrome c efflux and they indicate that the absence of CIF is the biochemical
      explanation for the impaired ability of HCW-2 cells to activate caspase-3 and
      undergo apoptosis.

PMID- 10200499
TI  - Cancer cell sensitization to fas-mediated apoptosis by sodium butyrate.
AB  - Cancer cells often resist Fas-mediated apoptosis even when the Fas receptor is
      expressed at the cell surface. We show here that human and rat colon cancer cells
      undergo massive apoptosis when they are exposed to soluble Fas ligand in the
      presence of sodium butyrate, an agent that induces by itself only a low rate of
      apoptosis. Sodium butyrate potentiates Fas-dependent apoptosis in seven out of
      eight colon cancer cell lines. Sodium butyrate does not increase Fas receptor
      cell surface expression and does not modify cell levels of Bcl-2, Bcl-xL, Bcl-xS
      and Bax. Sodium butyrate also induces tumor cell sensitization to the apoptotic
      effect of the combination of TNF-alpha and IFN-gamma, but it does not modify the
      level of the FADD/Mort1 adaptator molecule, at the connection between Fas- and
      TNF-dependent apoptosis pathways. Because the clinical toxicity of butyrate is
      low, its ability to enhance Fas-signal delivery in cancer cells could be of
      therapeutic interest.

PMID- 10200500
TI  - Perforin-dependent nuclear entry of granzyme B precedes apoptosis, and is not a
      consequence of nuclear membrane dysfunction.
AB  - Killer lymphocytes utilize the synergy of a membranolytic protein, perforin, and
      the serine protease granzyme B (grB) to induce target cell apoptosis, however the
      mechanism of this synergy remains incompletely defined. We have previously shown
      that perforin specifically induces the redistribution of cytoplasmic grB into the
      nucleus of dying cells, however a causal role for nuclear targeting of grB in
      cell death has not been demonstrated. In the present study, we used confocal
      laser scanning microscopy (CLSM) to determine whether the nuclear accumulation of
      fluoresceinated (FITC-) grB precedes or is a consequence of apoptosis. Two
      distinct and mutually exclusive cellular responses were observed in FDC-P1 cells:
      (i) up to 50% of the cells rapidly accumulated FITC-grB in the nucleus (maximal
      at 7 min; t1/2 of 2 min) and underwent apoptosis; (ii) the remaining cells took
      up FITC-grB only into the cytoplasm, and escaped apoptosis. Under these
      conditions, DNA fragmentation was not observed for at least 13 min, indicating
      nuclear accumulation of grB preceded the execution phase of apoptosis.
      Furthermore, nuclear import of grB proceeded through an intact nuclear membrane,
      as the nuclei of cells whose cytoplasm was pre-loaded with 70 kDa FITC-dextran
      excluded dextran for up to 90 min while still undergoing apoptosis in response to
      perforin and grB. These findings indicated that perforin-induced nuclear
      accumulation of grB precedes apoptosis, and is not a by-product of caspase
      induced nuclear membrane degradation. The cell membrane lesions formed by
      perforin in these experiments were not large enough to permit a 13 kDa protein
      (yeast cdk p13suc) access into the cytoplasm, but an 8 kDa protein (bacterial
      azurin) was able to equilibrate between the cytosol and the exterior. Therefore,
      transmembrane pores large enough to allow passive diffusion of grB (32 kDa) into
      the cell are not necessary for apoptosis. Rather, a perforin-dependent signal
      results in a redistribution of grB from the cytoplasm to the nucleus, where it
      may contribute to the nuclear changes associated with apoptosis.

PMID- 10200501
TI  - Expression of the lymphotoxin beta receptor on follicular stromal cells in human
      lymphoid tissues.
AB  - The lymphotoxin beta receptor (LTbetaR), and its ligand, LTalpha1beta2, have been
      proposed to play a key role in the development and organization of lymphoid
      tissues. The LTbetaR is expressed on a variety of human primary and transformed
      cells, but strikingly absent on T or B lymphocytes and primary monocytes or
      peripheral dendritic cells, although LTbetaR is detected on some myeloid leukemic
      lines. In the developing thymus LTbetaR is prominent along the trabeculae and
      into the medulla upto corticomedullary junction. In the spleen, LTbetaR is
      prominently expressed by cells in the red pulp and along the borders of red and
      white pulp which colocalizes with reticular stromal cells. The LTbetaR is
      expressed on a human follicular dendritic cell line, FDC-1, and signals
      expression of CD54 when ligated with the LTalpha1beta2 complex. These results
      support the concept that directional interactions between LTalpha1beta2 bearing
      lymphocytes and LTbetaR bearing stromal cells are involved in the organization of
      lymphoid tissue.

PMID- 10200502
TI  - Bax-alpha promotes apoptosis induced by cancer chemotherapy and accelerates the
      activation of caspase 3-like cysteine proteases in p53 double mutant B lymphoma
      Namalwa cells.
AB  - Stable transfected human p53 (mt/mt) B lymphoma Namalwa variant lines showing
      differential expression of the Bax-alpha protein were derived under hygromycin
      selection. Overexpression of Bax-alpha in these variant cells accelerates cell
      death induced by short or continuous treatments with various concentrations of
      camptothecin, etoposide, vinblastine and shows no accelerating cell death
      activity in cis-platinum and paclitaxel-treated cells. Activation of apoptosis
      and oligonucleosome-sized DNA fragmentation was observed in the variant lines
      with more pronounced effect in cells containing high level of Bax-alpha protein.
      These results suggest that increased cell death mediated by anticancer drugs
      correlates with Bax-alpha level of expression and that Bax-alpha sensitizes
      Namalwa cells treated at low drug concentrations. The extent of DNA synthesis
      inhibition following DNA topoisomerase inhibitor treatments was similar in
      control and all transfected Namalwa cells suggesting that Bax-alpha acts
      downstream of DNA topoisomerase-mediated DNA strand breaks. To define further the
      relation between Bax-alpha expression and apoptosis activation, kinetics of
      caspase activation was measured in drug-treated cells. Caspase activities were
      measured using specific fluorogenic peptide derivatives DABCYL-YVADAPV-EDANS and
      Ac-DEVD-AMC, substrates of the caspase 1-like and caspase 3-like families,
      respectively. In control and Bax-alpha transfected Namalwa cells no increase in
      caspase 1-like activity was detected following camptothecin and etoposide
      treatments. In contrast, a significant difference in Ac-DEVD-AMC hydrolysis
      activity was observed in Bax-alpha transfected Namalwa cells compared to that of
      control Namalwa cells after camptothecin and etoposide treatment. Increased
      caspase 3-like activity correlated also with poly(ADPribosyl) polymerase
      cleavage. Taken together, these results suggest that Bax-alpha sensitize B
      lymphoma cells to series of anticancer drugs and accelerates the activation of
      apoptotic protease cascade.

PMID- 10200503
TI  - Mycoplasma nucleases able to induce internucleosomal DNA degradation in cultured
      cells possess many characteristics of eukaryotic apoptotic nucleases.
AB  - It was previously shown (Paddenberg et al (1996) Eur J Cell Biol 69, 105 - 119)
      that cells of established lines like NIH3T3 fibroblasts and the human pancreatic
      adenocarcinoma PaTu 8902 line only degrade their chromatin at internucleosomal
      sites after an apoptotic stimulus when infected with Mycoplasma hyorhinis. In
      order to distinguish mycoplasma nucleases (Mr 47 - 54 kDa) from already described
      eukaryotic apoptotic enzymes, the mycoplasma nucleases were partially purified
      from serum-free culture supernatants and further characterized. Here we
      demonstrate directly that the enriched mycoplasma nucleases were able to fragment
      the DNA of nuclease-negative substrate nuclei at internucleosomal sites. The DNA
      degradation was accompanied by morphological changes typical of apoptosis like
      chromatin condensation and margination followed by shrinkage of the nuclei. The
      biochemical characterization revealed that the mycoplasma nucleases had a neutral
      to weakly basic pH-optimum. They required both calcium and magnesium in the mM
      range for maximal activation and were inhibited by zinc chloride, EGTA and EDTA.
      In two dimensional zymograms they migrated as three spots with isoelectic points
      between 8.1 and 9.5. They were not inhibited by monomeric actin. Our data also
      demonstrate that nuclear extracts prepared from nuclei isolated from Mycoplasma
      hyorhinis infected cells contained the mycoplasma nuclease activities leading to
      their internucleosomal DNA-degradation after incubation in the presence of
      calcium and magnesium.

PMID- 10200504
TI  - Cell death in the avian blastoderm: resistance to stress-induced apoptosis and
      expression of anti-apoptotic genes.
AB  - We investigated the expression of an apoptotic cell death program in blastodermal
      cells prior to gastrulation and the susceptibility of these cells to stress
      induced cell death. A low frequency (3.1%) of apoptotic blastodermal cells was
      observed in Hoechst 33342-vitally stained cytological preparations of complete
      blastoderms from unincubated eggs. These cells showed the stereotypic features of
      apoptosis including a progression of nuclear changes, cell shrinkage and
      blebbing, and the formation of apoptotic bodies. Prolonged storage of eggs at 12
      degrees C induced apoptosis in blastodermal cells (14%). A modest amount of
      apoptosis (10%) was also induced at the heat shock temperature of 48 degrees C,
      but not at 45 degrees C. Etoposide and other potent cytotoxic drugs failed to
      induce apoptosis in the blastodermal cells after 4 h of exposure. Progressively
      more apoptosis was induced at 8 and 24 h, but it did not exceed 35% of the cells.
      We detected transcripts for the anti-apoptotic genes bcl-2, bcl-xL, and hsp70.
      The developmental expression of these genes, especially hsp70, correlated with
      the delayed and limited stress-induction of apoptosis. These studies reveal the
      capacity of pre-streak blastodermal cells to engage in apoptosis and their
      relative resistance to stress conditions. This may be due to the prominent
      expression of hsp70 and/or multiple cell death genes which primarily antagonize
      cell death.

PMID- 10200505
TI  - DATELINE Aix-les-bains.

PMID- 10200506
TI  - The mitochondrion as an integrator/coordinator of cell death pathways.

PMID- 10200507
TI  - Argos induces programmed cell death in the developing Drosophila eye by
      inhibition of the Ras pathway.

PMID- 10200508
TI  - Phagocytic clearance of apoptotic cells: food for thought.

PMID- 10200510
TI  - Apoptosis: the importance of being eaten.
AB  - In vivo, cells undergoing apoptosis are usually recognised and swiftly ingested
      by macrophages or neighbouring cells acting as semi-professional phagocytes. This
      review debates evidence that the contents of apoptotic cells represent a danger
      to the organism, being capable of injuring tissue directly or triggering
      autoimmune responses, concluding that phagocytic clearance of intact apoptotic
      cells is a safe disposal route. Indeed, new data suggest that, in certain
      circumstances, phagocytes ingesting apoptotic cells may actively downregulate
      inflammatory and immune responses. Consequently, increasing evidence that there
      may be factors capable of perturbing safe clearance of apoptotic cells in vivo
      suggests that failure of this process may be a hitherto unrecognised pathogenetic
      factor in inflammatory and autoimmune diseases. New treatments designed to
      promote safe phagocytic clearance of dying cells can be anticipated, and it may
      even prove possible to eliminate unwanted cells by inducing appearance of cell
      surface 'eat me' signals.

PMID- 10200509
TI  - The role of phosphatidylserine in recognition of apoptotic cells by phagocytes.
AB  - Exposure of phosphatidylserine on the outer leaflet of the plasma membrane is a
      surface change common to many apoptotic cells. Normally restricted to the inner
      leaflet, phosphatidylserine appears as a result of decreased aminophospholipid
      translocase activity and activation of a calcium-dependent scramblase.
      Phosphatidylserine exposure has several potential biological consequences, one of
      which is recognition and removal of the apoptotic cell by phagocytes. It is still
      not clear which receptors mediate PS recognition on apoptotic cells; however,
      several interesting candidates have been proposed. These include the Class B
      scavenger and thrombospondin receptor CD36, an oxLDL receptor (CD68), CD14,
      annexins, beta2 glycoprotein I, gas-6 and a novel activity expressed on
      macrophages stimulated with digestible particles such as beta-glucan. Whether PS
      is the sole ligand recognized by phagocytes or whether it associated with other
      molecules to form a complex ligand remains to be determined.

PMID- 10200512
TI  - Inhibition versus induction of apoptosis by proteasome inhibitors depends on
      concentration.
AB  - We previously established that NF-kappaB DNA binding activity is required for
      Sindbis Virus (SV)-induced apoptosis. To investigate whether SV induces nuclear
      translocation of NF-kappaB via the proteasomal degradation pathway, we utilized
      MG132, a peptide aldehyde inhibitor of the catalytic subunit of the proteasome.
      20 microM MG132 completely abrogated SV-induced NF-kappaB nuclear activity at
      early time points after infection. Parallel measures of cell viability 48 h after
      SV infection revealed that 20 microM MG132 induced apoptosis in uninfected cells.
      In contrast, a lower concentration of MG132 (200 nM) resulted in partial
      inhibition of SV-induced nuclear NF-kappaB activity and inhibition of SV-induced
      apoptosis without inducing toxicity in uninfected cells. The specific proteasomal
      inhibitor, lactacystin, also inhibited SV-induced death. Taken together, these
      results suggest that the pro-apoptotic and anti-apoptotic functions of peptide
      aldehyde proteasome inhibitors such as MG-132 depend on the concentration of
      inhibitor utilized and expand the list of stimuli requiring proteasomal
      activation to induce apoptosis to include viruses.

PMID- 10200511
TI  - Anti-apoptotic potential of insect cellular and viral IAPs in mammalian cells.
AB  - IAPs were identified as baculoviral proteins that could inhibit the apoptotic
      response of insect cells to infection. Of the viral IAPs, OpIAP and CpIAP can
      inhibit apoptosis, whereas AcIAP cannot. OpIAP and some mammalian homologues can
      inhibit mammalian cell death. Two mammalian IAPs bind to TNFRII associated
      factors (TRAFs), but the significance of this is unclear. Here we show that
      Drosophila cellular IAPs and two baculoviral IAPs (OpIAP and CpIAP) can inhibit
      mammalian cell death induced by overexpression of Caspases 1 and 2. IAPs must act
      on conserved components of the apoptotic mechanism, but as none of these IAPs
      could bind TRAF proteins, TRAFs are not likely to be important for IAP mediated
      apoptosis inhibition. As OpIAP protected against death induced by ligation of TNF
      receptor family members, but not by factor nor serum withdrawal from dependent
      cells, it can inhibit certain apoptotic pathways without affecting others.

PMID- 10200513
TI  - Differential p53 phosphorylation and activation of apoptosis-promoting genes Bax
      and Fas/APO-1 by irradiation and ara-C treatment.
AB  - In this study, we examined the effects of radiation and ara-C on induction of
      apoptosis and on the apoptosis-promoting genes p53, Bax and Fas/APO-1, in BV173
      human leukemia cells, which harbor the wild-type p53 gene. It has been reported
      that p53 upregulates Fas/APO-1 and Bax expression. Both irradiation and ara-C
      treatment resulted in apoptosis and induction of p53 proteins within hours. The
      Bax gene was activated in irradiated and ara-C-treated BV173 cells, but Fas/APO-1
      was induced only in irradiated BV173 cells. Radiation and ara-C treatment did not
      induce Bax or Fas/APO-1 protein expression in p53-null HL60 cells. Radiation
      weakly induced Fas/APO-1 expression in KBM-7 cells, which harbor a partially
      defective p53 gene. Both HL60 and KBM-7 cells are more resistant to radiation-
      and ara-C-induced apoptosis than BV173 cells. These results suggest that
      functional p53 is necessary for the activation of Bax and Fas/APO-1 expression.
      However, elevated p53 protein is not sufficient to activate Fas/APO-1 gene
      expression in ara-C-treated cells. Using two-dimensional gel electrophoresis, we
      found that the p53 proteins in irradiated and ara-C-treated BV173 cells have
      different isoelectric points; they converged to a single isoelectric point after
      in vitro treatment with phosphatase. These results suggest that different
      genotoxic treatments cause different phosphorylations of p53, which may account
      for the different levels of activation of Fas/APO-1 expression.

PMID- 10200514
TI  - Teratogen-induced cell death in postimplantation mouse embryos: differential
      tissue sensitivity and hallmarks of apoptosis.
AB  - Teratogen-induced cell death is a common event in the pathogenesis associated
      with tissues destined to be malformed. Although the importance of this cell death
      is recognized, little information is available concerning the biochemistry of
      teratogen-induced cell death. We show that three teratogens, hyperthermia,
      cyclophosphamide and sodium arsenite induce an increase in cell death in day 9.0
      mouse embryos with concurrent induction of DNA fragmentation, activation of
      caspase-3 and the cleavage of poly (ADP-ribose) polymerase (PARP). Teratogen
      induced cell death is also selective, i. e., some cells within a tissue die while
      others survive. In addition, cells within some tissues die when exposed to
      teratogens while cells in other tissues are relatively resistant to teratogen
      induced cell death. An example of the latter selectivity is seen in the cells of
      the developing heart, which are resistant to the cytotoxic potential of many
      teratogens. We show that the absence of cell death in the heart is accompanied by
      the complete lack of DNA fragmentation, activtion of caspase-3 and the cleavage
      of PARP.

PMID- 10200515
TI  - Cisplatin effects on F-actin and matrix proteins precede renal tubular cell
      detachment and apoptosis in vitro.
AB  - In primary cultures of porcine proximal tubular kidney cells and LLC-PK1 cells
      cisplatin (5 - 50 microM) caused apoptosis and cell detachment; in both systems
      cell detachment occurred, preceded by a loss of cytoskeletal F-actin stress
      fibers within 4 - 6 h, and a reduction of mRNA encoding for fibronectin, collagen
      a2 type (IV) and laminin B2 within 17 - 41 h. Prevention of F-actin damage by
      phalloidin prevented nuclear fragmentation, suggesting a relation between F-actin
      damage and apoptosis. Overexpression of Bcl-2 also prevented apoptosis, but did
      not prevent damage to the F-actin skeleton or the reduction of mRNA expression of
      the matrix proteins. These results suggest that Bcl-2 overexpression interferes
      with apoptotic signals downstream of F-actin. The relevance of these results for
      cell detachment in kidney toxicity is discussed.

PMID- 10200516
TI  - Prohibitin and RACK homologues are up-regulated in trypanosomes induced to
      undergo apoptosis and in naturally occurring terminally differentiated forms.
AB  - Two genes have been identified as up-regulated late during ConA-induced apoptosis
      in procyclic form Trypanosoma brucei rhodesiense. The first represents a
      homologue of prohibitin, a proto-oncogene originally described in mammals and
      subsequently in yeast, which is involved in cell-cycle control and senescence.
      The Trypanosoma prohibitin homologue appears to contain within it a putative
      death domain. The second gene, homologous to a family of regulatory proteins
      which are receptors for activated protein kinase C (RACKs), is also shown to be
      up-regulated in terminally differentiated bloodstream form trypanosomes. These
      are the first endogenous genes to be identified as up-regulated in programmed
      cell death (PCD) in unicellular organisms.

PMID- 10200517
TI  - The stress-response proteins poly(ADP-ribose) polymerase and NF-kappaB protect
      against bile salt-induced apoptosis.
AB  - Bile salts induce apoptosis and are implicated as promoters of colon cancer. The
      mechanisms by which bile salts produce these effects are poorly understood. We
      report that the cytotoxic bile salt, sodium deoxycholate (NaDOC), activates the
      key stress response proteins, NF-kappaB and poly(ADP-ribose) polymerase (PARP).
      The activation of NF-kappaB and PARP, respectively, indicates that bile salts
      induce oxidative stress and DNA damage. The pre-treatment of cells with specific
      inhibitors of these proteins [pyrrolidine dithiocarbamate (NF-kappaB inhibitor)
      and 3-aminobenzamide (PARP inhibitor)] sensitizes cells to the induction of
      apoptosis by NaDOC, indicating that these stress response pathways are protective
      in nature. Colon cancer risk has been reported to be associated with resistance
      to apoptosis. We found an increase in activated NF-kappaB at the base of human
      colon crypts that exhibit apoptosis resistance. This provides a link between an
      increased stress response and colon cancer risk. The implications of these
      findings with respect to apoptosis and to colon carcinogenesis are discussed.

PMID- 10200518
TI  - Caspase-mediated activation of PAK2 during apoptosis: proteolytic kinase
      activation as a general mechanism of apoptotic signal transduction?
AB  - p21-activated kinase 2 (PAK2) is proteolytically cleaved during apoptosis through
      the action of DEVD-sensitive caspase(s). This cleavage event causes PAK2
      activation, and PAK2 activity is implicated in regulation of the biochemistry and
      morphology of the apoptotic cell. PAK2 is just one example of a number of
      identified caspase targets that are protein kinases involved in regulating
      various aspects of cell function. We hypothesize that this may reflect their
      important role in regulating the controlled and orderly demise of the dying cell.

PMID- 10200519
TI  - Apoptosis: unmasking the executioner.
AB  - The execution phase of apoptosis is comprised of those processes that commit
      cells to apoptotic death. Many independent studies have implicated mitochondria
      as playing a critical role in apoptotic execution. The activation of caspase-3
      and subsequent late stage degradative events are probably triggered by the
      release of proteins (such as cytochrome c) from the intermembrane space of
      mitochondria. The mechanisms responsible for this release are controversial but
      may include mitochondrial permeability transition and bcl-2-regulated swelling of
      the mitochondrial matrix. Two theoretical models of execution are discussed. It
      is important to note that some critical features of these models are largely
      based on data acquired from cell-free studies. Further studies with intact cells
      are urgently needed to test the physiological validity of these models.

PMID- 10200520
TI  - Interaction of viral proteins with host cell death machinery.
AB  - In recent years, intense research has been directed towards understanding
      molecular mechanisms involved in viral pathogenesis. It is now known that many
      viruses manipulate host defense mechanisms to prevent apoptosis in order to
      maximize viral replication. Towards the end of their replication cycle, certain
      viruses direct the synthesis of proteins that induce apoptosis or cell lysis
      thereby facilitating viral release from the cell. The present review summarizes
      the current understanding of interactions between viral proteins and the host
      cell death machinery.

PMID- 10200521
TI  - Apoptosis induced by microinjection of cytochrome c is caspase-dependent and is
      inhibited by Bcl-2.
AB  - Microinjection of cytochrome c induced apoptosis in all the cell types we tested
      (IPC-81, Swiss 3T3, Clone 8 fibroblasts, NRK, H295, Y1, HEK 293). The apoptotic
      phenotype induced by injected cytochrome c was characterized by externalization
      of phosphatidyl serine, cell detachment from substratum and from neighbor cells,
      and had the classic ultrastructural features of membrane budding, chromatin
      condensation and cell shrinkage. Depending on the cell type and concentration of
      cytochrome c, the induction of apoptosis was remarkably rapid. The development of
      apoptosis was prevented by the caspase inhibitor Z-VAD.fmk. Four of the cell
      types (Clone 8, Swiss 3T3, NRK, Y1) were transfected with bcl-2 and these all
      showed a markedly decreased sensitivity towards injected cytochrome c. Our data
      suggest that extramitochondrial cytochrome c is a general apoptogen in cells with
      a functioning caspase system. They also indicate that, in preventing apoptosis,
      Bcl-2 acts not only at the level of regulation of cytochrome c release from
      mitochondria, but can also interfere with caspase activation induced by
      cytochrome c microinjected directly into the cytoplasm.

PMID- 10200522
TI  - The role of the tumor suppressor p53 in spermatogenesis.
AB  - The p53 protein appeared to be involved in both spermatogonial cell proliferation
      and radiation response. During normal spermatogenesis in the mouse, spermatogonia
      do not express p53, as analyzed by immunohistochemistry. However, after a dose of
      4 Gy of X-rays, a distinct p53 staining was present in spermatogonia, suggesting
      that, in contrast to other reports, p53 does have a role in spermatogonia. To
      determine the possible role of p53 in spermatogonia, histological analysis was
      performed in testes of both p53 knock out C57BL/6 and FvB mice. The results
      indicate that p53 is an important factor in normal spermatogonial cell production
      as well as in the regulation of apoptosis after DNA damage. First, p53 knock out
      mouse testes contained about 50% higher numbers of A1 spermatogonia, indicating
      that the production of differentiating type spermatogonia by the undifferentiated
      spermatogonia is enhanced in these mice. Second, 10 days after a dose of 5 Gy of
      X-rays, in the p53 knock out testes, increased numbers of giant sized
      spermatogonial stem cells were found, indicating disturbance of the apoptotic
      process in these cells. Third, in the p53 knock out testis, the differentiating
      A2-B spermatogonia are more radioresistant compared to their wild-type controls,
      indicating that p53 is partly indispensable in the removal of lethally irradiated
      differentiating type spermatogonia. In accordance with our immunohistochemical
      data, Western analysis showed that levels of p53 are increased in total adult
      testis lysates after irradiation. These data show that p53 is important in the
      regulation of cell production during normal spermatogenesis either by regulation
      of cell proliferation or, more likely, by regulating the apoptotic process in
      spermatogonia. Furthermore, after irradiation, p53 is important in the removal of
      lethally damaged spermatogonia.

PMID- 10200523
TI  - Differences in epitope accessibility of p53 monoclonal antibodies suggest at
      least three conformations or states of protein binding of p53 protein in human
      tumor cell lines.
AB  - The p53 tumor suppressor gene is deleted or mutated in over 50% of human tumors.
      Mutations frequently extend the half-life of the p53 protein; and a high level of
      nuclear p53 expression, detected by immunohistochemistry, has been used to
      predict the p53 status of tumors. We compared the sensitivity and reactivity of
      five frequently used, commercially available monoclonal antibodies (1801, DO1,
      DO7, BP53.12 and 421) in immunoblot and immunofluorescence assays, and found that
      results differed among the antibodies. Comparison of immunoblot analysis of
      denatured nuclear and cytoplasmic p53 protein were consistent with antibodies
      DO1, DO7 and BP53.12, each of which generated a strong specific signal in both
      cell fractions. However, in situ analysis demonstrated that although all
      antibodies recognized nuclear p53, only BP53.12 and 421 recognized p53 protein in
      the cytoplasm. In addition, 1801 produced a signal in p53-negative tumor cell
      lines. Differences in situ among the antibodies were probably due to the
      accessibility of their respective epitopes and suggested that nuclear and
      cytoplasmic p53 either have different three-dimensional conformations or are
      bound to different proteins. A third p53 protein conformation was also suggested
      by the observation that only two of the five antibodies (BP53.12 and DO7)
      detected induced levels of p53 in situ following exposure to ionizing radiation.
      In summary, except for the fact that DO7 does not recognize cytoplasmic p53 in
      situ, we found it to be the most specific, versatile, and reliable antibody. We
      conclude that the p53 antibody of choice depends upon the specific goal of a
      study and the method used to detect this protein.

PMID- 10200524
TI  - Irradiation induces G2/M cell cycle arrest and apoptosis in p53-deficient
      lymphoblastic leukemia cells without affecting Bcl-2 and Bax expression.
AB  - The tumor suppressor p53 has been implicated in gamma irradiation-induced
      apoptosis. To investigate possible consequences of wild-type p53 loss in
      leukemia, we studied the effect of a single dose of gamma irradiation upon p53
      deficient human T-ALL (acute lymphoblastic leukemia) CCRF - CEM cells. Exposure
      to 3 - 96 Gy caused p53-independent cell death in a dose and time-dependent
      fashion. By electron microscopic and other criteria, this cell death was
      classified as apoptosis. At low to intermediate levels of irradiation, apoptosis
      was preceded by accumulation of cells in the G2/M phase of the cell division
      cycle. Expression of Bcl-2 and Bax were not detectably altered after irradiation.
      Expression of the temperature sensitive mouse p53 V135 mutant induced apoptosis
      on its own but only slightly increased the sensitivity of CCRF - CEM cells to
      gamma irradiation. Thus, in these, and perhaps other leukemia cells, a p53- and
      Bcl-2/Bax-independent mechanism is operative that efficiently senses irradiation
      effects and translates this signal into arrest in the G2/M phase of the cell
      cycle and subsequent apoptosis.

PMID- 10200525
TI  - Increased sensitivity to cis-diamminedichloroplatinum induced apoptosis with
      mitochondrial DNA depletion.
AB  - Malignant cells harbor mechanisms which allow escape from drug-induced apoptosis,
      and the drug-resistance phenotype can be significantly associated with resistance
      to programmed cell death. There is accumulating evidence that mitochondria play a
      role in the tumorigenic phenotype, including the relative resistance to
      apoptosis. Whether changes at the mitochondrial level per se, would impact on the
      relative sensitivity of malignant cells to undergo drug-induced apoptosis, is not
      know. Accordingly, we determined if depleting mitochondrial DNA (mtDNA) would
      change the susceptibility of U937 cells to undergo apoptosis. With depletion,
      increases in sensitivity to cis-diamminedichoroplatinum (cisplatin)-induced
      apoptosis was observed. This sensitivity could be reverted to the parental
      phenotype by transforming the depleted cells with normal platelet mitochondria.
      mRNA expression of BAX, BCL2, MDR1, MRP, ERCC1 and ERCC2, putatively associated
      with cisplatin resistance to apoptotic death was unchanged. Inhibition of
      mitochondrial ATP production by oligomycin did not result in a change in ATP
      levels, indicating energetics were not playing a role in the observed phenotype
      changes. All U937 cells (with/without mtDNA) continued to respond to cisplatin by
      an apoptotic death. MtDNA-encoded molecules may be playing a role in the relative
      sensitivity of cells to undergo a cisplatin-induced apoptotic death, but may not
      be required for cells to undergo apoptosis per se.

PMID- 10200526
TI  - Onset of apoptotic DNA fragmentation can precede cell elimination by days in the
      small intestinal villus.
AB  - DNA fragmentation is a hallmark of apoptosis, and has been viewed as a short
      lived process (<hour) that immediately precedes cell elimination. However, use of
      sensitive techniques like in situ end-labelling plus (ISEL+) has indicated that
      the period between the initiation of detectable fragmentation and cell
      elimination could be longer (days). To address this possibility, we used a model
      system of cell death and replacement, the murine small intestinal villus. Pulses
      of 5-bromo-2'-deoxyuridine were used to follow quantitatively cohorts of cells
      from their generation in the crypts to their elimination at the villus tips,
      resulting in a temporal 'yard-stick' where position on the villus indicated time
      before cell elimination; these data allowed a mathematical description of cell
      movement and clearance. Combining these data with ISEL+ quantitation, enterocytes
      were found to commence and maintain DNA fragmentation 2 - 3 days before
      elimination, a phenomenon that likely has relevance to studies on apoptosis also
      in other systems.

PMID- 10200527
TI  - Selective induction of apoptosis in Philadelphia chromosome-positive chronic
      myelogenous leukemia cells by an inhibitor of BCR - ABL tyrosine kinase, CGP
      57148.
AB  - The BCR - ABL tyrosine kinase has been implicated as the cause of Philadelphia
      chromosome (Ph1)-positive leukemias. We report herein that CGP 57148, a selective
      inhibitor of the ABL tyrosine kinase, caused apoptosis specifically in bcr - abl
      positive chronic myelogenous leukemia (CML) cells, K562 and KYO-1. Upon treatment
      with CGP 57148, CRKL, a specific substrate for BCR - ABL that propagates signals
      via phosphatidylinositol-3' kinase (PI3K), was dephosphorylated, indicating
      inhibition of BCR - ABL tyrosine kinase at the cellular level. Likewise,
      MAPK/ERK, a downstream mediator of Ras, was also dephosphorylated. Caspase
      activation and cleavage of retinoblastoma protein (pRB) accompanied the
      development of CGP 57148-induced apoptosis. Inhibition of caspase suppressed
      apoptosis and the cleavage of pRB, and in turn arrested cells in the G1 phase.
      These results indicate that CGP 57148 shows apoptogenic and anti-proliferative
      effects on bcr - abl-positive cells by blocking BCR - ABL-initiated signaling
      pathways.

PMID- 10200528
TI  - Differentiation or death: the view from Versailles.

PMID- 10200529
TI  - Apoptosis: who was first?

PMID- 10200530
TI  - Bacterial toxins and the Rho GTP-binding protein: what microbes teach us about
      cell regulation.
AB  - In the present review activities of two bacterial toxins, Clostridium botulinum
      exoenzyme C3 and Escherichia coli CNF1, both acting on the GTP-binding protein
      Rho are analyzed. Proteins belonging to the Rho family regulate the actin
      cytoskeleton and act as molecular switches in a number of signal transduction
      pathways. C3 and CNF1 have opposite effects on Rho thus representing useful tools
      for studies on cell division, cell differentiation and apoptosis.

PMID- 10200531
TI  - Proteolytic cleavage of ras GTPase-activating protein during apoptosis.
AB  - p120-ras GTPase-activating protein (rasGAP) associates with Ras and negatively
      regulates Ras signaling by stimulating the intrinsic rate of Ras GTPase activity.
      rasGAP also associates with other cellular signaling proteins which suggest that
      rasGAP may play a role in coordinating other signal transduction pathways.
      Disruption of rasGAP in vivo results in extensive apoptosis. Fas-mediated
      apoptosis results in the activation of caspases that cleave cellular substrates
      which are important for maintaining cytoplasmic and nuclear integrity. We show
      here that rasGAP is proteolytically cleaved by caspases early in Fas-induced
      apoptosis of Jurkat cells. rasGAP was also cleaved by DNA-damaging
      chemotherapeutic agents and TNF-related apoptosis inducing ligand (TRAIL), also
      known as Apo2L. Based on the size of the products generated by cleavage of
      deletion mutants of rasGAP we predict that cleavage of rasGAP occurs in the
      hydrophobic region and between the SH2(2) and ras-p21 interacting domain which
      would leave an intact ras-p21 interacting domain. Interestingly, cleavage of
      rasGAP in vitro enhanced rasGAP hydrolysis activity. Our results demonstrate that
      diverse apoptotic stimuli cause caspase-mediated cleavage of rasGAP early in
      apoptosis.

PMID- 10200532
TI  - The CD95/CD95 ligand system is not the major effector in anticancer drug-mediated
      apoptosis.
AB  - Many anticancer drugs are able to induce apoptosis in tumor cells but the
      mechanisms underlying this phenomenon are poorly understood. Some authors
      reported that the p53 tumor suppressor gene may be responsible for drug-induced
      apoptosis; however, chemotherapy-induced apoptosis can also be observed in p53
      negative cells. Recently, doxorubicin (DXR) was reported to induce CD95L
      expression to mediate apoptosis through the CD95/CD95L system. Thus, an
      impairment of such a system may be involved in drug resistance. We evaluated the
      in vitro antitumor activity of several cytotoxic drugs on two human p53-negative
      T-cell lymphoma cell lines, the HUT78-B1 CD95L-resistant cell line and the HUT78
      parental CD95L-sensitive cell line. We demostrated by Western blotting assay that
      DXR and etoposide (VP-16) were able to induce CD95L expression after 4 h of
      treatment. In contrast, they were unable to induce the expression of p53. DXR, at
      concentrations ranging from 0.001 - 1 microg/ml, and VP16, at concentrations
      ranging from 0.05 - 1 microg/ml, were equally cytotoxic and induced apoptosis in
      both cell lines as assessed by fluorescence microscopy and flow cytometry
      analyses. Although we observed a slightly reduced percentage of apoptotic cells
      in HUT78B1 when compared with the parental HUT78 cells after few hours of drug
      exposure, this difference was no longer evident at 48 or 72 h. Similarly, the
      exposure of HUT78 cells to a CD95-blocking antibody partially reduced early
      apoptosis (24 h) without affecting the long-term effects of the drugs including
      cytotoxicity. Furthermore, as observed with DXR and VP-16, both the CD95L
      sensitive and the CD95L-resistant cell lines resulted equally sensitive to the
      cytotoxic effects of a number of different cytotoxic drugs (vincristine,
      camptothecin, 5-fluorouracil and methotrexate). The treatment with the Caspase-3
      tetrapeptide aldehyde inhibitor, Ac-DEVD-CHO, did not affect the DXR-induced
      apoptosis whereas it only modestly inhibited apoptosis and cytotoxicity of VP-16,
      while Z-VAD.FMK, a Caspase inhibitor that prevents the processing of Caspase-3 to
      its active form, was able to block DXR-induced apoptosis at 24 h but not at 48 h.
      Thus, our results do not confirm a crucial role for the CD95/CD95L system in drug
      induced apoptosis and suggest the involvement of alternative p53-independent
      pathways at least in this experimental model system.

PMID- 10200533
TI  - Fas and Fas-mediated effects on a human salivary cell line in vitro: a model for
      immune-mediated exocrine damage in Sjogren's syndrome.
AB  - Sjogren's syndrome (SS) is an autoimmune exocrinopathy characterized by
      mononuclear cell infiltration and loss of parenchymal tissue in salivary and
      lacrimal glands. The mechanisms for these histologic alterations are not known.
      Apoptotic cell death, induced by the ligation of Fas (APO-1/CD95) with Fas ligand
      (FasL/CD95L) may be an explanation for the tissue damage seen in SS. Fas and FasL
      were detected in minor salivary glands from SS patients and healthy individuals
      using immunohistochemical methods. There was increased expression of both Fas and
      FasL in the patients. The ability of the Fas-FasL pathway to influence epithelial
      cell growth and survival was demonstrated in vitro using a human submandibular
      cell line. The presence of Fas receptor was demonstrated on the cells. Anti-Fas
      antibody triggered cell death. Cells were also grown in the presence of gamma
      interferon (IFN-gamma). IFN-gamma induced an upregulation of Fas receptor
      expression and pre-treatment of cells with IFN-gamma led to enhanced anti-Fas
      mediated cell death.

PMID- 10200534
TI  - Increased spontaneous in vitro apoptosis in double negative T cells of humans
      with a fas/apo-1 mutation.
AB  - We describe a 17 year old patient suffering from Canale-Smith syndrome (CSS)
      including chronic lymphadenopathy, splenomegaly, hypergammaglobulinemia and
      recurrent Coombs positive hemolytic crises. The parents are not consanguine, all
      other family members including two brothers are healthy. Peripheral blood
      mononuclear cells of the patient showed an increased rate of CD3 positive,
      CD4/CD8 double negative T-lymphocytes. In vitro assays showed these cells to have
      an increased rate of spontaneous apoptosis. Though expression of Fas/Apo-1 (CD95)
      and Fas-ligand (FasL) was detected on RNA- and protein level we found Fas/Apo-1
      mediated apoptosis being significantly reduced. Sequencing of the fas/apo-1 gene
      proved the patient RT and his father to carry a point mutation at position 804
      located in exon 9 (death domain) leading to an amino acid substitution. For
      developing of CSS, a fas/apo-1 mutation seems to be necessary but not sufficient.
      An additional independent mechanism must be involved in the pathogenesis of human
      lpr<-phenotype.

PMID- 10200535
TI  - TNFalpha-mediated cell death is independent of cdc25A.
AB  - Tumor necrosis factor (TNFs) have been shown to be synthesized by ovarian
      carcinomas, and may therefore affect tumor cells in an autocrine manner.
      Therefore, we investigated the effects of recombinant TNFs on ovarian carcinoma
      cells N.1 and examined expression of the proto-oncogenes c-myc and cdc25A which
      are known to play a prominent role in apoptosis. TNFalpha elicited apoptosis in
      N.1 cells within 72 h which was shown by typical morphological changes, DNA
      fragmentation and signature type cleavage of poly(ADP-ribose) polymerase into a
      89 kDa proteolytic peptide. TNFalpha-induced apoptosis was accompanied by
      constitutive c-Myc expression, although the mRNA level of phosphatase cdc25A was
      suppressed within 24 h of TNFalpha treatment and the protein level decreased
      after 48 h. Cdc25A tyrosine phosphatase is an activator of the cdk2-cyclin E
      complex which allows for cell cycle progression. As expected, we found TNFalpha
      mediated Cdc25A down-regulation to inhibit Cdk2 activity. Cdc25A suppression was
      related to TNFalpha-induced apoptosis but not to a TNFalpha-induced G0 arrest
      because cyclin D1 expression was unaffected and the gene gas6 (growth arrest
      specific 6) was not induced. Arresting cells by treatment with genistein
      prevented TNFalpha-triggered apoptosis and inhibited c-myc expression. TNFalpha
      induced apoptosis is not accompanied by cell cycle arrest which may be due to
      constitutive c-Myc expression, although Cdc25A and Cdk2 activity is also down
      regulated. High c-Myc and low Cdc25A activity might present conflicting signals
      to the cell cycle machinery which are incompatible with cell survival.

PMID- 10200536
TI  - Expression of AML1-d, a short human AML1 isoform, in embryonic stem cells
      suppresses in vivo tumor growth and differentiation.
AB  - The human AML1 gene encodes a heterodimeric transcription factor which plays an
      important role in mammalian hematopoiesis. Several alternatively spliced AML1
      mRNA species were identified, some of which encode short protein products that
      lack the transactivation domain. When transfected into cells these short isoforms
      dominantly suppress transactivation mediated by the full length AML1 protein.
      However, their biological function remains obscure. To investigate the role of
      these short species in cell proliferation and differentiation we generated
      embryonic stem (ES) cells overexpressing one of the short isoforms, AML1-d, as
      well as cells expressing the full length isoforms AML1-b and AML2. The in vitro
      growth rate and differentiation of the transfected ES cells were unchanged.
      However, overexpression of AML1-d significantly affected the ES cells' ability to
      form teratocarcinomas in vivo in syngeneic mice, while a similar overexpression
      of AML1-b and AML2 had no effect on tumor formation. Histological analysis
      revealed that the AML1-d derived tumors were poorly differentiated and contained
      numerous apoptotic cells. These data highlight the pleiotropic effects of AML1
      gene products and demonstrate for the first time an in vivo growth regulation
      function for the short isoform AML1-d.

PMID- 10200537
TI  - Non-cell autonomous induction of apoptosis and loss of posterior structures by
      activation domain-specific interactions of Oct-1 in the Xenopus embryo.
AB  - Oct-1, a member of the POU family of transcription factors, is expressed at
      relatively high levels in ectodermal and mesodermal cell lineages during early
      Xenopus embryogenesis (Veenstra et al, 1995). Here we show that overexpression of
      Oct-1 induces programmed cell death concomitant with the loss of the posterior
      part of the body axis. Truncated Oct-1 variants, missing either the C-terminal or
      N-terminal trans-activation domain, exhibit a different capacity to cause such
      developmental defects. Oct-1-induced cell death is rescued in unilaterally
      injected embryos by non-injected cells, indicative of the non-cell autonomous
      character of the developmental effects of Oct-1. This was confirmed by marker
      gene analysis, which showed a significant decrease in brachyury expression,
      suggesting that Oct-1 interferes with an FGF-type signalling pathway.

PMID- 10200538
TI  - Apoptosis induced by N-hexanoylsphingosine in CHP-100 cells associates with
      accumulation of endogenous ceramide and is potentiated by inhibition of
      glucocerebroside synthesis.
AB  - We report that apoptosis induced by N-hexanoylsphingosine (C6-Cer) in CHP-100
      human neuroepithelioma cells associates with accumulation of
      monohexosylsphingolipids produced not only by short-chain ceramide glycosylation
      but also through glycosylation of a ceramide pool endogenously produced. By high
      performance thin layer chromatography on borate silica gel plates, newly formed
      monohexosylsphingolipids were identified as glucosylceramides (GluCer); however,
      accumulation of lactosylceramide or higher-order glycosphingolipids was not
      observed. GluCer accumulation was fully suppressed by D-threo-1-phenyl-2
      decanoylamino-3-morpholino-1-propanol; moreover, while this inhibitor had no
      effect on cell viability when administered alone, it markedly potentiated the
      apoptotic effect of C6-Cer. These results provide evidence that activation of
      GluCer synthesis is an important mechanism through which CHP-100 cells attempt to
      escape ceramide-induced apoptosis.

PMID- 10200540
TI  - Apoptosis and autoimmunity: two sides to the coin.

PMID- 10200539
TI  - UVA exposure of human skin reconstructed in vitro induces apoptosis of dermal
      fibroblasts: subsequent connective tissue repair and implications in photoaging.
AB  - The skin reconstructed in vitro has been previously shown to be a useful model to
      investigate the effects of UVB exposure (Bernerd and Asselineau, 1997). The
      present study describes the response to UVA irradiation. Major alterations were
      observed within the dermal compartment. Apoptosis of fibroblasts located in the
      superficial area of the dermal equivalent was observed as soon as 6 h after
      irradiation, leading to their disappearance after 48 h. This effect was obtained
      without major alterations of epidermal keratinocytes suggesting a differential
      cell type sensitivity to UVA radiations. In addition, collagenase I was secreted
      by dermal fibroblasts. The UVA dermal effects could be observed even after
      removal of the epidermis during the post irradiation period, demonstrating that
      they were independent of the keratinocyte response. The analysis of the tissue
      regeneration during the following 2 weeks revealed a connective tissue repair via
      fibroblasts proliferation, migration and active synthesis of extracellular matrix
      proteins such as fibronectin and procollagen I. This cellular recolonization of
      the superficial part of the dermal equivalent was due to activation of surviving
      fibroblasts located deeply in the dermal equivalent. The direct damage in the
      dermis and the subsequent connective tissue repair may contribute to the
      formation of UVA-induced dermal alterations.

PMID- 10200541
TI  - Prothymosin alpha antisense oligonucleotides induce apoptosis in HL-60 cells.

PMID- 10200542
TI  - Autoantigens as substrates for apoptotic proteases: implications for the
      pathogenesis of systemic autoimmune disease.
AB  - Systemic autoimmune diseases are a genetically complex, heterogeneous group of
      diseases in which the immune system targets a diverse, but highly specific group
      of intracellular autoantigens. The clustering and marked concentration of these
      molecules in the surface blebs of apoptotic cells, and their modification by
      apoptosis-specific proteolytic cleavage and/or phosphorylation at these sites,
      has focused attention on a unique apoptotic setting as the potential initiating
      stimulus for systemic autoimmunity. This apoptotic event is likely to (i) occur
      in a microenvironment containing high concentrations of the targeted antigens,
      (ii) be pro-immune in nature (e.g. viral infection), and (iii) allow
      suprathreshold concentrations of antigen with non-tolerized structure (either
      novel fragments, post-translational modifications, or complexes) to enter the
      class II processing pathway and initiate a primary immune response. Defective
      clearance or reduced anti-inflammatory consequences of apoptotic material may be
      important susceptibility factors in this group of diseases. Once the primary
      immune response to apoptotic antigens has been initiated, other apoptotic events
      (occurring in the course of homeostasis or damage) may stimulate the secondary
      immune response with less stringency, resulting in flares.

PMID- 10200543
TI  - Apoptosis in the effector phase of autoimmune diabetes, multiple sclerosis and
      thyroiditis.
AB  - The immune system is unusual in two respects. It produces billions of new cells
      daily that traffic throughout the body and cells within the system proliferate
      rapidly following exposure to an infectious agent. Both of these attributes
      require that cell production be regulated by cell death. Human diseases
      characterized by accelerated cell death leading to immunodeficiency disorders or
      by reduced cell death leading to systemic autoimmune diseases have been
      identified. In certain autoimmune diseases, the immune system directs its
      powerful cytotoxic effector mechanisms against specialized cells such as
      oligodendrocytes in multiple sclerosis, the beta cells of the pancreas in
      diabetes mellitus and thyrocytes in Hashimoto's thyroiditis. In this review, we
      examine the cytotoxic effector pathways implicated in cell death in organ
      specific autoimmune disorders.

PMID- 10200544
TI  - Possible role of NF-kappaB and p53 in the glutamate-induced pro-apoptotic
      neuronal pathway.
AB  - Apoptosis is now recognized as an important component in many progressive and
      acute neurodegenerative diseases. Extracellular signals and intracellular
      mechanisms triggering and regulating apoptosis in neuronal cells are still a
      matter of investigation. Here we review data from our and other laboratories with
      the aim to elucidate the nature of some proteins which are known to be involved
      in cell cycle regulation as well as in promoting degeneration and apoptosis of
      neurons. The following molecules will be taken into consideration: NF-kappaB,
      p53, p21 and MSH2. These proteins are activated by neurotoxic experimental
      conditions which involve the stimulation of selective receptors for the
      excitatory aminoacid glutamate. Thus, we hypothesize their contribution to an
      intracellular pathway responsible for the glutamate-induced neuronal death.
      Identification of such mechanisms could be relevant for understanding the
      apoptosis associated with various neurodegenerative diseases as well as for
      developing novel strategies of pharmacological intervention.

PMID- 10200545
TI  - Photodynamic therapy: a mitochondrial inducer of apoptosis.
AB  - Photodamage to the mitochondria of murine leukemia P388 cells resulted in
      immediate loss of the mitochondrial membrane potential together with the release
      of cytochrome c into the cytosol. This was followed by a rapid activation of
      caspase 3-like proteases, as indicated by a marked rise in DEVDase activity.
      There was no significant effect on WEHDase or VEIDase activities, suggesting that
      only the late-stage caspases had been effected. The apoptotic response to
      mitochondrial photodamage was abolished by the broad-spectrum caspase inhibitor
      zVAD-fmk, but this did not prevent loss of viability after mitochondrial
      photodamage. These studies indicate that the release of cytochrome c from
      photodamaged mitochondria is sufficient to directly initiate a caspase-dependent
      apoptotic response.

PMID- 10200547
TI  - An elevated bax/bcl-2 ratio corresponds with the onset of prostate epithelial
      cell apoptosis.
AB  - The prostate gland in adult male rats is highly dependent on androgenic steroids.
      Castration initiates the regression of this tissue through a process involving
      the loss of the vast majority of cells by means of apoptosis. We studied this
      well characterized in vivo model of apoptosis to evaluate how the expression of
      two particular gene products, bcl-2 and bax, known to be important for the
      regulation of apoptosis were affected by castration. An RNase protection assay
      designed to quantify the levels of bax mRNA showed that this transcript was
      transiently elevated after castration, reaching a peak in expression at 3 days
      and declining thereafter. In contrast, bcl-2 mRNA expression was continuously
      elevated over a period of up to 7 days after castration. The distinct changes in
      the expression of the mRNAs encoding these two genes were confirmed by an in situ
      hybridization analysis of regressing rat ventral prostate tissues. The elevation
      in mRNAs were apparently restricted to the secretory epithelial cells of the
      gland, the cellular compartment of the tissue most affected by castration.
      Finally, SDS - PAGE/Western blot analysis of bax and bcl-2 protein expression in
      the regressing rat prostate gland with bax and bcl-2-specific antibodies showed
      that the changes in the bax and bcl-2 protein levels were similar and consistent
      to that found for the mRNAs. In summary, the expression of both bax and bcl-2
      gene products are uniquely modulated during castration-induced regression of the
      rat ventral prostate gland. The changes we observed identify a transient but
      marked increase in the bax/bcl-2 expression ratio of the tissue that peaks on the
      second and third days after castration, coinciding with the peak periods of
      prostate cell apoptosis. These data support previous studies done on in vitro
      systems wherein it was shown that the bax/bcl-2 ratio determines the apoptotic
      potential of a cell.

PMID- 10200546
TI  - Characterization of a mutant T-cell hybridoma line with defects in the TCR
      mediated apoptotic pathway.
AB  - A mutant T-cell hybridoma line named mutant 51 was developed that, unlike the
      parental line, did not die after T-cell receptor (TCR) engagement and
      demonstrated reduced death in response to dexamethasone. Intracellular calcium
      measurements showed that available calcium stores were markedly reduced in the
      mutant cell line. Unlike control cells, secretion of IL-2 from mutant cells was
      also greatly reduced, although addition of exogenous IL-2 did not facilitate
      increased apoptosis. Although levels of the cell death gene product Nur77 were
      equivalent, additional studies showed that mutant cells expressed Nur77
      predominantly in the cytoplasm following TCR engagement, while parental cells
      displayed a nuclear translocalization of Nur77. In addition, Fas levels and Fas
      ligand dependant killing were both markedly reduced in the mutant clone. From
      these data we hypothesize a role for available calcium stores and Nur77 nuclear
      localization in TCR-mediated apoptosis in T-cell hybridomas.

PMID- 10200548
TI  - Alterations in cell death and cell cycle progression in the UV-irradiated
      epidermis of bcl-2-deficient mice.
AB  - The effect of bcl-2 gene ablation on epidermal cell death induced by UV-B
      irradiation was investigated in mice. Exposure of depilated back skin of bcl-2-/-
      mice to 0.5 J/cm2 UV-B caused a prolonged increase in the number of epidermal
      cells showing nuclear DNA fragmentation compared to wild-type littermates.
      Consistently, skin explants from bcl-2-deficient mice exhibited a higher number
      of sunburn cells per cm epidermis (16.6+/-2.1 vs 7.0+/-1.5) following exposure to
      0.1 J/cm2 UV-B in vitro. Furthermore, UV irradiation failed to increase pre
      melanosomes in skin explants from mutant animals, and primary menalocyte cultures
      derived from bcl-2 null mutants were highly susceptible to UV-induced cell death
      compared to cultures from wild-type littermates. An accelerated reappearance of
      proliferating cells, showing nuclear immunoreactivity for Ki-67 and c-Fos, was
      observed in the UV-irradiated epidermis of bcl-2-deficient mice. Taken together,
      these findings suggest that effects of UV radiation on epidermal cell death and
      cell cycle progression are influenced by survival-promoting Bcl-2.

PMID- 10200550
TI  - The role of macrophage cell death in tuberculosis.
AB  - Studies of host responses to infection have traditionally focused on the direct
      antimicrobial activity of effector molecules (antibodies, complement, defensins,
      reactive oxygen and nitrogen intermediates) and immunocytes (macrophages,
      lymphocytes, and neutrophils among others). The discovery of the systems for
      programmed cell death of eukaryotic cells has revealed a unique role for this
      process in the complex interplay between microorganisms and their cellular
      targets or responding immunocytes. In particular, cells of the
      monocyte/macrophage lineage have been demonstrated to undergo apoptosis following
      intracellular infection with certain pathogens that are otherwise capable of
      surviving within the hostile environment of the phagosome or which can escape the
      phagosome. Mycobacterium tuberculosis is a prototypical 'intracellular parasite'
      of macrophages, and the direct induction of macrophage apoptosis by this organism
      has recently been reported from several laboratories. This paper reviews the
      current understanding of the mechanism and regulation of macrophage apoptosis in
      response to M. tuberculosis and examines the role this process plays in
      protective immunity and microbial virulence.

PMID- 10200549
TI  - Apoptosis in hematopoietic cells (FL5.12) caused by interleukin-3 withdrawal:
      relationship to caspase activity and the loss of glutathione.
AB  - The mechanism of cell death caused by cytokine deprivation remains largely
      unknown. FL5.12 cells (a murine prolymphocytic cell line), following interleukin
      3 (IL-3) withdrawal, undergo a decrease in intracellular glutathione (GSH) that
      precedes the onset of apoptosis. In the present study, the induction of apoptosis
      following IL-3 withdrawal or GSH depletion with DL-buthionine-[S,R,]-sulfoximine
      (BSO) was examined. Both conditions caused time-dependent increases in
      phosphatidylserine externalization, acridine orange and ethidium bromide
      staining, decreases in mitochondrial membrane potential, processing and
      activation of caspase-3 and proteolysis of the endogenous caspase substrate
      poly(adenosine diphosphate ribose)polymerase (PARP). Apoptosis induced by IL-3
      deprivation but not BSO also caused lamin B1 cleavage, suggesting activation of
      caspase-6. Despite a more profound depletion of GSH after BSO than withdrawal of
      IL-3, the extent of apoptosis was somewhat lower. Benzyloxycarbonyl-Val-Ala
      Asp(OMe)fluoromethyl ketone (z-VAD.fmk) blocked this caspase activity and
      prevented cell death after BSO exposure but not after IL-3 deprivation. Following
      IL-3 withdrawal, the caspase inhibitors z-VAD.fmk and boc
      asp(OMe)fluoromethylketone (boc-asp.fmk) prevented the cleavage and activation of
      caspase-3, the breakdown of lamin B1 and partially mitigated PARP degradation.
      However, the externalization of phosphatidylserine, the fall in mitochondrial
      membrane potential and subsequent apoptotic cell death still occurred. These
      results suggest that IL-3 withdrawal may mediate cell death by a mechanism
      independent of both caspase activation and the accompanying loss of GSH.

PMID- 10200551
TI  - Dexamethasone induces apoptosis in human T cell clones expressing low levels of
      Bcl-2.
AB  - Previous results of ours have demonstrated that the same clonotype can express
      both a sensitive and a resistant phenotype to Dex-mediated PCD induction
      depending on its cell cycle phase. In particular, we demonstrated that human T
      lymphocytes, arrested in the G0/G1 phase of the cell cycle, are susceptible,
      while proliferating T cells are resistant to Dex-mediated apoptosis. In this
      paper, we have further characterized the sensitive and resistant phenotypes and
      investigated whether a different expression of the apoptotic genes Fas, FasL, Bcl
      2, Bcl-x and Bax is involved in the regulation of Dex-mediated apoptosis. The
      results show that the amount of Bcl-2 expression, that changes during cell cycle
      phases, determines susceptibility or resistance to apoptosis induced by Dex. In
      fact, undetectable expression of Bcl-2 in sensitive cells favors Dex-mediated
      apoptosis while high expression of Bcl-2 in proliferating cells counterbalances
      apoptosis induction. Moreover, the addition of exogenous IL-2, in the presence of
      Dex, fails to up-regulate Bcl-2 expression and to revert Dex-mediated apoptotic
      phenomena.

PMID- 10200552
TI  - IL-2 deprivation triggers apoptosis which is mediated by c-Jun N-terminal kinase
      1 activation and prevented by Bcl-2.
AB  - A variety of environmental stresses, as well as inflammatory cytokines, induce
      activation of c-Jun N-terminal kinases. We describe here that IL-2 deprivation
      induced apoptosis in TS1alphabeta cells does not modify c-Jun protein levels and
      correlates Bcl-2 downregulation and an increase in JNK1, but not JNK2, activity
      directly related to the induction of apoptosis. Indeed, downregulation of JNK1
      expression using antisense oligonucleotides inhibits apoptosis induced by IL-2
      withdrawal. Overexpression of Bcl-2 promotes cell survival and blocks JNK1
      activation as well as apoptosis caused by IL-2 deprivation. This suggests that
      inhibition of the JNK1 signaling pathway may be a mechanism through which Bcl-2
      promotes cell survival and prevents apoptosis triggered by growth factor
      withdrawal.

PMID- 10200553
TI  - Mammary development in health and disease: Biochemical Society Symposium 63edited
      by P.S. Rudland, D.G. Fernig and S.J. Leinster.

PMID- 10200554
TI  - Identification of two novel mRNA splice variants of bax.

PMID- 10200555
TI  - Emerging roles of caspase-3 in apoptosis.
AB  - Caspases are crucial mediators of programmed cell death (apoptosis). Among them,
      caspase-3 is a frequently activated death protease, catalyzing the specific
      cleavage of many key cellular proteins. However, the specific requirements of
      this (or any other) caspase in apoptosis have remained largely unknown until now.
      Pathways to caspase-3 activation have been identified that are either dependent
      on or independent of mitochondrial cytochrome c release and caspase-9 function.
      Caspase-3 is essential for normal brain development and is important or essential
      in other apoptotic scenarios in a remarkable tissue-, cell type- or death
      stimulus-specific manner. Caspase-3 is also required for some typical hallmarks
      of apoptosis, and is indispensable for apoptotic chromatin condensation and DNA
      fragmentation in all cell types examined. Thus, caspase-3 is essential for
      certain processes associated with the dismantling of the cell and the formation
      of apoptotic bodies, but it may also function before or at the stage when
      commitment to loss of cell viability is made.

PMID- 10200556
TI  - On the complexities of ceramide changes in cells undergoing apoptosis: lack of
      evidence for a second messenger function in apoptotic induction.
AB  - The generation of cellular ceramides as a second messenger has been implicated as
      a regulatory and required step for the induction of apoptosis. In this study, we
      have applied a recently developed mass spectrometric technique to the
      determination of changes in physiological ceramide levels during apoptosis
      induced by tumor necrosis factor plus cycloheximide in U937 cells and the
      chemical agents anisomycin or geranylgeraniol in HL-60 cells. The mass
      spectrometric method has significant advantages over traditional methods for
      ceramide quantitation in that it determines the relative abundance of all
      ceramide species present in complex biological lipid mixtures individually and
      simultaneously. We quantitiated ceramides ranging from C14 to C26, finding that
      their basal levels and relative distribution varied significantly, both within
      and between different cell types. However, we were not able to detect any
      significant changes in either total ceramide content or species distribution
      until 1 h or more post-stimulation with any of these treatments, by which time
      the cells were in an advanced stage of apoptosis. Differences were also seen
      between all three treatments in the ceramide species distribution observed in
      these late stages of apoptosis. These data indicate that in vivo ceramide
      generation occurs as a consequence of apoptosis rather than as an essential
      second messenger involved in its induction. They also pose new questions about
      the potential roles that certain ceramide species may play in the late stages of
      apoptosis, and demonstrate a clear need to utilize the resolving power of mass
      spectrometry-based assays in any future investigations into the biological
      function of ceramides.

PMID- 10200557
TI  - Relationships of apoptotic signaling mediated by ceramide and TNF-alpha in U937
      cells.
AB  - It is commonly assumed that ceramide is a second messenger that transduces
      signaling leading to apoptosis. We tested this hypothesis by investigating the
      role of ceramide in TNF-alpha-initiated apoptotic signaling using the histiocytic
      lymphoma cell line U937. We found considerable differences between cell killing
      by TNF-alpha and by ceramide. U937 cells treated with TNF-alpha are committed
      early and irreversibly to the apoptotic pathway and start to die 90 min after
      treatment. U937 cells treated with ceramide start to die 12 h after the initial
      treatment. The cell death signaling initiated by TNF-alpha is transduced within
      minutes of exposure to TNF-alpha and it is irreversible. Exogenous ceramide
      increases the intracellular level of ceramide rapidly, significantly, and well
      above the physiological levels, within minutes, but cellular commitment to death
      does not occur until after the first 6 h of incubation. Furthermore, the
      endogenous ceramide in U937 cells treated with TNF-alpha increases well after the
      commitment to the apoptotic pathway. The differences between ceramide and TNF
      alpha in the kinetics and the commitment to the apoptotic pathway suggest that,
      (a) ceramide is not a second messenger in the apoptotic signaling of TNF-alpha,
      (b) ceramide elevations, in TNF-alpha treated cells, are a consequence rather
      than a cause of apoptosis and (c) exogenously added ceramide and TNF-alpha kill
      cells via different pathways.

PMID- 10200558
TI  - Alix, a novel mouse protein undergoing calcium-dependent interaction with the
      apoptosis-linked-gene 2 (ALG-2) protein.
AB  - ALG-2 is a EF hand calcium binding protein with sequence homologies to
      calmodulin. Vito et al have shown that ALG-2 expression is required for apoptosis
      following a number of death stimuli,1 although nothing is known about the
      effectors which underlie ALG-2 function. Here we have used ALG-2 as bait in a
      yeast two hybrid screen of a mouse brain cDNA library. We found that ALG-2 binds
      to itself and to a novel protein that we call ALG-2 interacting protein X, Alix.
      Using co-immunoprecipitation experiments, we confirmed ALG-2/ALG-2 binding and
      demonstrated that this interaction is calcium independent. ALG-2/Alix interaction
      was also validated by co-immunoprecipitation, but in this case, the binding was
      found to be strictly calcium dependent. Alix seems highly conserved throughout
      evolution since it shows significant homologies to a putative C. elegans protein
      (YNK-1) and to proteins of A. nidulans (PalA) and S. cerevisiae (BRO1). Alix is a
      potential regulator or downstream effector of ALG-2 action.

PMID- 10200559
TI  - JNK/SAPK activity contributes to TRAIL-induced apoptosis.
AB  - We report here that JNK/SAPKs are activated by TRAIL in parallel to induction of
      apoptosis in human T and B cell lines. Death signaling as well as JNK/SAPK
      activation by TRAIL in these cells is FADD- and caspase-dependent since dominant
      negative FADD or the caspase inhibitor zVAD prevented both, apoptosis and
      JNK/SAPK activity. JNK/SAPK activity in response to triggering of CD95 by an
      agonistic antibody (alphaAPO-1) was also diminished by dominant-negative FADD or
      zVAD. Correspondingly, a cell line resistant to alphaAPO-1-induced death
      exhibited crossresistance to TRAIL-induced apoptosis and did not upregulate
      JNK/SAPK activity in response to TRAIL or alphaAPO-1. Inhibition of JNK/SAPK
      activity, by stably transfecting cells with a dominant-negative JNKK-MKK4
      construct, reduced apoptosis in response to TRAIL or alphaAPO-1. Therefore,
      activation of JNK/SAPKs by TRAIL or alphaAPO-1 occurs downstream of FADD and
      caspases and contributes to apoptosis in human lymphoid cell lines.

PMID- 10200561
TI  - Expression of tissue transglutaminase in the developing chicken limb is
      associated both with apoptosis and endochondral ossification.
AB  - The cross-linking enzyme tissue transglutaminase (tTG) participates in a variety
      of cellular functions. To assess its contribution to extracellular and
      intracellular processes during development we cloned the cDNA for chicken heart
      tissue transglutaminase and localized the sites of transglutaminase expression by
      in situ hybridization and immunohistochemistry. Compared with the chicken red
      blood cell transglutaminase cDNA, the heart cDNA encodes a transglutaminase with
      an amino-terminal truncation. The truncated enzyme retains full catalytic
      activity and is GTP-inhibitable. Tissue transglutaminase expression was observed
      in developmentally transient structures in embryonic chicken limb at day 7.5 of
      incubation suggesting that its expression is dynamically regulated during limb
      morphogenesis. The major morphogenetic events of the limb associated with
      transglutaminase expression were cartilage maturation during skeletal
      development, interdigital apoptosis, and differentiation of skeletal muscle.
      Maturation of the cartilage during endochondral ossification was characterized by
      intra- and extracellular transglutaminase accumulation in the zone of
      hypertrophic chondrocytes. Only intracellular enzyme could be detected in
      mesenchymal cells of the prospective joints, in apoptotic cells of the
      interdigital web, and in skeletal muscle myoblasts. An apparently constitutive
      expression of tissue transglutaminase was found in vascular endothelial cells
      corresponding to the adult expression pattern. The dynamic pattern of
      transglutaminase expression during morphogenesis suggests that tissue remodeling
      is a major trigger for transglutaminase induction.

PMID- 10200560
TI  - Programmed cell death without DNA fragmentation in the jimpy mouse: secreted
      factors can enhance survival.
AB  - Jimpy is one of many related mutations affecting the myelin proteolipid protein
      gene that causes severe hypomyelination in the central nervous system (CNS).
      Underlying the hypomyelination is a failure of oligodendrocytes (OLs) to
      differentiate, and the premature death of large numbers of OLs during the
      developmental period. Previous light and electron microscopic evidence suggested
      that jimpy OLs die in a manner consistent with programmed cell death. We have
      used TUNEL staining as a biochemical marker for apoptosis in conjunction with
      immunostaining for OL and myelin markers. At 13 - 14 days postnatal, a time when
      the number of dying OLs in jimpy CNS is increased more than five times normal,
      there are only modest increases (70% in spinal cord; 20% in cerebral cortex) in
      TUNEL labeled cells in mutant CNS tissues. The results in vitro are similar, and
      only a small per cent of TUNEL labeled cells have the antigenic phenotype of OLs.
      The discrepancy between numbers of dying and TUNEL labeled cells suggests either
      that most jimpy OLs do not undergo programmed cell death or that the biochemical
      pathways leading to their death do not involve DNA fragmentation which is
      detected by the TUNEL method. We also present evidence that jimpy OLs show
      increased survival and enhanced differentiation when they are grown in vitro in
      medium conditioned by cells lines which express products of the proteolipid
      protein gene. Cell lines expressing proteolipid protein and the alternatively
      spliced DM20 protein have differential effects on cell numbers and production of
      myelin-like membranes.

PMID- 10200562
TI  - Selective induction of apoptosis by capsaicin in transformed cells: the role of
      reactive oxygen species and calcium.
AB  - Capsaicin is a vanilloid quinone analog that inhibits the plasma membrane
      electron transport (PMOR) system and induces apoptosis in transformed cells.
      Using a cytofluorimetric approach we have determined that capsaicin induces a
      rapid increase of reactive oxygen species (ROS) followed by a subsequent
      disruption of the transmembrane mitochondrial potential (DeltaPsim) and DNA
      nuclear loss in transformed cell lines and in mitogen activated human T cells.
      This apoptotic pathway is biochemically different from the typical one induced by
      either ceramide or edelfosine where, in our system, the DeltaPsim dissipation
      precedes the generation of reactive oxygen species. Neither production of ROS nor
      apoptosis was found in capsaicin-treated resting T cells where the activity of
      the PMOR system is minimal when compared with mitogen activated or transformed T
      cells. Capsaicin also induces Ca2+ mobilization in activated but not in resting T
      cells. However, preincubation of cells with BAPTA-AM, which chelate cytosolic
      free calcium, did not prevent ROS generation or apoptosis induced by capsaicin,
      suggesting that ROS generation in capsaicin treated cells is not a consequence of
      calcium signaling and that the apoptotic pathway may be separated from the one
      that mobilizes calcium. Moreover, we present data for the implication of a
      possible vanilloid receptor in calcium mobilization, but not in ROS generation.
      These results provide evidence that the PMOR system may be an interesting target
      to design antitumoral and anti-inflammatory drugs.

PMID- 10200563
TI  - Bcl-XL induction during terminal differentiation of friend erythroleukaemia cells
      correlates with delay of apoptosis and loss of proliferative capacity but not
      with haemoglobinization.
AB  - Friend murine erythroleukaemia (F-MEL) cells are a useful model for studying the
      processes that regulate erythroid differentiation since exposure of these cells
      to chemical inducers (DMSO or HMBA) results in commitment to terminal cell
      division and synthesis of haemoglobin. This study examined the relationship
      between differentiation and apoptosis in DMSO sensitive and resistant F-MEL
      cells. Clear apoptosis was not observed in DMSO-treated sensitive F-MEL (strain
      745A) cells during the induction of differentiation. In contrast, DMSO-induced
      745A cells exhibited delayed apoptosis compared to uninduced cells. Since the Bcl
      2 family members play a major role in the control of apoptosis and/or
      differentiation, we determined their expression before and after DMSO or HMBA
      treatment. Neither untreated nor chemically-induced 745A cells expressed the Bcl
      2 protein. The levels of Bax and Bad proteins remained relatively constant during
      DMSO-induced differentiation. DMSO or HMBA treatment of 745A cells induced a
      marked increase of Bcl-XL expression during the late phase of differentiation
      which persisted even when the cells began to die. This upregulation of Bcl-XL was
      independent of cell density but was correlated with cell arrest in G0/G1. DMSO
      treatment induced a similar delay of apoptosis and enhancement of Bcl-XL
      expression in F-MEL (strain TFP10) cells which fail to synthesize haemoglobin in
      the presence of DMSO. Dexamethasone, which blocks DMSO-induced differentiation of
      F-MEL cells, prevented the induction of Bcl-XL. Inhibitors such as imidazole or
      succinylacetone, which inhibit haemoglobin synthesis but not commitment to
      terminal cell division, did not suppress Bcl-XL induction in DMSO-induced cells.
      Taken together, these results indicate that DMSO treatment of F-MEL cells induces
      a marked increase in Bcl-XL expression suggesting a role for this anti-apoptotic
      protein in the process of erythroid differentiation in F-MEL cells. Moreover,
      induction of Bcl-XL during this process seems to be associated with loss of
      proliferative capacity rather than with haemoglobin synthesis.

PMID- 10200565
TI  - Exposure of phosphatidylserine is a general feature in the phagocytosis of
      apoptotic lymphocytes by macrophages.
AB  - Although different macrophages exploit different cell surface receptors to
      recognize apoptotic lymphocytes, indirect evidence suggested that the
      phosphatidylserine (PS) that appears on the surface of lymphocytes undergoing
      apoptosis participates in specific recognition by all types of macrophages. To
      test this possibility directly, annexin V, a protein that specifically binds to
      PS, was used to mask this phospholipid on the apoptotic cell surface.
      Preincubation of apoptotic lymphocytes with annexin V blocked phagocytosis by
      elicited mouse peritoneal macrophages, macrophages of the mouse J774 cell line
      and mouse bone marrow macrophages. Similarly, annexin V was able to inhibit
      phagocytosis of lipid-symmetric erythrocytes, another target cell upon which PS
      is exposed. Together these results demonstrate directly that macrophages of all
      types depend on the PS exposed on the surface of apoptotic lymphocytes for
      recognition and phagocytosis.

PMID- 10200564
TI  - Adenovirus-mediated expression of Fas ligand induces apoptosis of human prostate
      cancer cells.
AB  - Several laboratories have reported on the apoptotic potentials of human prostate
      cancer (PC) cell lines in response to crosslinking of Fas (CD95/APO-1) with
      agonistic anti-Fas antibodies. We have re-evaluated the apoptotic potentials of
      seven human PC cell lines using the natural Fas ligand (FasL) in place of
      agonistic antibody. First, PC cell lines were tested in a standard cytotoxicity
      assay with a transfected cell line that stably expresses human FasL. Next, we
      developed an adenoviral expression system employing 293 cells that stably express
      crmA, a poxvirus inhibitor of apoptosis, to analyze the effects of FasL when
      expressed internally by the PC cell lines. Our data suggest that the apoptotic
      potentials of these cell lines were greatly underestimated in previous studies
      utilizing agonistic anti-Fas antibodies. Lastly, adenoviral-mediated expression
      of FasL prevented growth and induced regression of two human PC cell lines in
      immunodeficient mice. These preliminary in vivo results suggest a potential use
      for adenovirus encoding FasL as a gene therapy for PC.

PMID- 10200567
TI  - Life and death in a medieval atmosphere.

PMID- 10200566
TI  - Inhibition of transforming growth factor beta1-induced hepatoma cell apoptosis by
      liver tumor promoters: characterization of primary signaling events and effects
      on CPP32-like caspase activity.
AB  - The effects of the liver tumor promoters phenobarbital, clofibrate, dieldrin, and
      DDT on transforming growth factor-beta1 (TGFbeta)-induced apoptosis were studied
      in FTO-2B hepatoma cells. Inhibition of apoptosis by these compounds was strongly
      correlated with a decrease in CPP32-like caspase activity. Similar effects were
      obtained with insulin and dexamethasone. CPP32-like activity may thus provide a
      useful tool for quantiation of apoptosis under various treatment conditions.
      Diverse effects on apoptosis-associated cellular signaling proteins were
      observed: insulin led to an activation of the MAP kinases ERK1/2, of PKB/Akt and
      of NF-kappaB, phenobarbital and clofibrate enhanced NF-kappaB activity solely,
      while dexamethasone slightly enhanced NF-kappaB activity and increased the
      expression of Bcl-xL. Since inhibition of apoptosis was still detectable if the
      anti-apoptotic compounds were administered more than 10 h after TGFbeta, the
      diverse primary signals appear to converge at a presumably late stage of
      apoptosis, but upstream of activation of CPP32 or related caspases.

PMID- 10200568
TI  - Challenging the dogmas.

PMID- 10200569
TI  - Distinct cell killing properties of the Drosophila reaper, head involution
      defective, and grim genes.

PMID- 10200570
TI  - A remarkable 'death on the rocks' 

PMID- 10200571
TI  - Mapping and sequencing of the murine 'tissue' transglutaminase (Tgm2) gene:
      absence of mutations in MRLlpr/lpr mice.

PMID- 10200572
TI  - Phosphatidylserine externalization during differentiation-triggered apoptosis of
      erythroleukemic cells.
AB  - K562 erythroleukemia cells undergo apoptosis when induced to differentiate along
      the erythroid lineage with hemin. This event, characterized by DNA fragmentation,
      correlated with downregulation of the survival protein, BCL-xL, and decrease in
      mitochondrial transmembrane potential (deltapsi[m]) that ultimately resulted in
      cell death. Reorientation of phosphatidylserine (PS) from the cells inner-to
      outer plasma membrane leaflet and inhibition of the aminophospholipid translocase
      was observed upon hemin-treatment. Constitutive expression of BCL-2 did not
      inhibit hemin-induced alterations in lipid asymmetry or decrease in deltapsi[m],
      and only moderately prevented DNA fragmentation. BCL-2, on the other hand,
      effectively inhibited actinomycin D-induced DNA fragmentation, the appearance of
      PS at the cells outer leaflet and the decrease in deltapsi[m]. The caspase
      inhibitor, z.VAD.fmk, blocked DNA fragmentation by both hemin and actinomycin D,
      but inhibited PS externalization only in the actinomycin D-treated cells. These
      results suggest that, unlike pharmacologically-induced apoptosis, PS
      externalization triggered by differentiation-induced apoptosis occurs by a
      mechanism that is associated with a decrease in deltapsi[m], but independent of
      BCL-2 and caspases.

PMID- 10200573
TI  - Small stress protein Hsp27 accumulation during dopamine-mediated differentiation
      of rat olfactory neurons counteracts apoptosis.
AB  - The small stress protein Hsp27 is expressed during mammalian neural development.
      We have analyzed the role of this protein in immortalized rat olfactory
      neuroblasts. In the presence of dopamine a fraction of these cells differentiate
      into neurons while the remaining cells undergo apoptosis. We report here that the
      dopamine induced differentiation and apoptosis are associated with a transient
      and specific accumulation of Hsp27. Moreover, transfection experiments have shown
      that Hsp27 overexpression drastically decreases the fraction of cells undergoing
      apoptosis. In contrast, reduction of the endogenous level of Hsp27 led to
      abortion of differentiation and, therefore, drastically increased the number of
      apoptotic cells. Furthermore, in the normal cell population we show that Hsp27
      accumulation takes place only in differentiating cells that were not undergoing
      apoptosis. We therefore conclude that Hsp27 may represent a key protein that
      controls the decision of olfactory precursor cells to undergo either
      differentiation or cell death.

PMID- 10200574
TI  - Differential involvement of DNases in HeLa cell apoptosis induced by etoposide
      and long term-culture.
AB  - We have applied to human HeLa cells two different stimuli of apoptosis: the
      antitumoral drug etoposide, and a more 'physiological' death condition, obtained
      by growing cells in the same medium for long time periods, for up to 10 days.
      Analysis of different parameters demonstrated that in both experimental systems
      the same apoptotic features are visible. However, the DNA degradation pattern
      appeared to be different, suggesting the involvement of different DNases. In this
      view, we have analyzed the activity and expression of Ca2+-Mg2+-dependent and
      acid DNases. We have observed that DNase I is not modulated during apoptosis. In
      contrast, the acid L-DNase II (derived from Leukocyte Elastase Inhibitor by post
      translational modification), recently identified in our laboratory, is mainly
      active in the apoptotic pathway induced by long term-culture. Furthermore, we
      have provided evidence that while caspase 3 is activated by both inducers,
      caspase 1 is essential only for the etoposide-induced apoptosis.

PMID- 10200575
TI  - De novo expression of the class-A macrophage scavenger receptor conferring
      resistance to apoptosis in differentiated human THP-1 monocytic cells.
AB  - The class-A macrophage scavenger receptor (MSR) is a trimeric multifunctional
      protein expressed selectively in differentiated monomyeloid phagocytes which
      mediates uptake of chemically modified lipoproteins and bacterial products. This
      study investigated whether MSR plays a role in the regulation of apoptosis, a
      model of genetically programmed cell death. De novo expression of MSR occurred in
      human THP-1 monocytic cells differentiated with phorbol esters, which activated a
      nuclear transcription factor binding to the Ap1/ets-like domain of the MSR
      promoter. The phorbol ester-stimulated THP-1 cells also expressed increased
      levels of the pro-apoptotic gene products, caspase-3 and Fas ligand, but the
      cells exhibited no change in apoptosis. Global activation of GTP-binding proteins
      with fluoride anions triggered apoptosis of THP-1 cells in a time- and
      concentration-dependent manner, demonstrated by nuclear shrinkage and
      fragmentation and internucleosomal DNA fragmentation. However, the MSR-expressing
      THP-1 macrophage-like cells showed a significant reduction in apoptosis compared
      to undifferentiated control THP-1 cells, which produce MSR at undetectable
      levels. Fluoride stimulation also triggered apoptosis of human Jurkat T cells.
      Stimulation with phorbol ester made no difference in apoptosis between treated
      and untreated Jurkat cells. Finally, Chinese hamster ovary (CHO) cells
      overexpressing the class-A MSR type I by cDNA transfection showed markedly
      increased resistance to G-protein-coupled apoptosis. Thus, de novo expression of
      MSR associated with monocyte maturation into macrophages appears to confer the
      resistance of macrophages to apoptotic stimulation by G-protein activation.

PMID- 10200576
TI  - Human skeletal muscle cytosols are refractory to cytochrome c-dependent
      activation of type-II caspases and lack APAF-1.
AB  - Apoptotic regulatory mechanisms in skeletal muscle have not been revealed. This
      is despite indications that remnant apoptotic events are detected following
      exercise, muscle injury and the progression of dystrophinopathies. The recent
      elicitation of a cytochrome c-mediated induction of caspases has led to
      speculation regarding a cytochrome c mechanism in muscle. We demonstrate that
      cytosols from skeletal muscle biopsies from healthy human volunteers lack the
      ability to activate type-II caspases by a cytochrome c-mediated pathway despite
      the confirmed presence of both procaspase-3 and -9. This was not due to the
      presence of an endogenous inhibitor, as the muscle cytosols enhanced caspase
      activity when added to a control cytosol, subsequently activated by cytochrome c
      and dATP. In addition, we demonstrate that muscle cytosols lack the apoptosis
      protease activator protein-1 (APAF-1), both at the protein and mRNA levels. These
      data indicate that human skeletal muscle cells will be refractory to
      mitochondrial-mediated events leading to apoptosis and thus can escape a major
      pro-apoptotic regulatory mechanism. This may reflect an evolutionary adaptation
      of cell survival in the presence of the profusion of mitochondria required for
      energy generation in motility.

PMID- 10200577
TI  - Regulation of phosphatidylserine exposure and phagocytosis of apoptotic T
      lymphocytes.
AB  - In lymphocytes, an asymmetric distribution of phospholipids across the plasma
      membrane is maintained by an ATP-dependent translocase which specifically
      transports aminophospholipids from the outer to the inner leaflet of the bilayer.
      During apoptosis, this enzyme is down-regulated and a lipid flipsite, termed the
      scramblase, is activated. Together, these events lead to the appearance of
      phosphatidylserine (PS) on the cell surface. In DO11.10 T lymphocyte hybridoma
      cells undergoing apoptosis, the kinetics of PS externalization are paralleled by
      the development of PS-sensitive phagocytosis by macrophages. This parallel is
      also observed when PS externalization is effected directly by application of a
      Ca2+ ionophore, suggesting that PS externalization is not only necessary, but
      sufficient, to generate a recognition signal. The broad spectrum aspartate
      directed cysteine protease (caspase) inhibitor zVAD-fmk blocks externalization of
      PS and terminal cell lysis after induction of apoptosis by anti-CD3 antibody, but
      is ineffective when apoptosis is induced in the same cells by treatment with
      glucocorticoid. These results suggest that apoptosis induced by glucocorticoid
      does not require the same zVAD-sensitive caspase steps which are required for
      Fas/FasL-dependent death induced by anti-CD3 antibody, and that the action of
      these proteases is also not required for PS externalization. Extracellular Ca2+
      is required to complete the later stages of apoptosis in DO11.10 cells, and its
      removal restores normal transport of PS, suggesting that down-regulation of the
      aminophospholipid translocase and up-regulation of the scramblase are not
      effected by irreversible protease cleavage.

PMID- 10200578
TI  - p53-mediated up-regulation of CD95 is not involved in genotoxic drug-induced
      apoptosis of human breast tumor cells.
AB  - Induction of CD95 (Fas/APO-1) and CD95 ligand during chemotherapeutic treatment
      may contribute to the death by apoptosis of some tumor cells. In this study, we
      have analyzed the role of the CD95 system in genotoxic drug-induced death of
      human breast tumor cells. Incubation of the breast tumor cell lines MCF-7 and
      EVSA-T with doxorubicin or methotrexate caused apoptosis after 48 h of treatment.
      These drugs induced a marked increase in the level of CD95 mRNA and protein in
      wild-type p53-expressing MCF-7 cells. On the contrary, the breast cancer cell
      line EVSA-T that expresses high levels of an inactive form of p53, did not up
      regulate CD95 upon drug treatment. Elevation of CD95 expression by DNA-damaging
      drugs was notably blocked in MCF-7 cells expressing the human papillomavirus type
      16 E6 protein (E6 cells) which prevented p53 accumulation upon DNA damage.
      However, E6 cells were still killed by the drugs. Furthermore, the genotoxic
      drugs did not induce the expression of CD95 ligand in MCF-7 cells at doses that
      caused apoptosis in these breast tumor cells. Moreover, drug-induced apoptosis of
      breast tumor cells was not prevented in the presence of either a CD95
      antagonistic antibody or a CD95 ligand blocking antibody. We also observed a
      strong synergism between lower doses of DNA-damaging drugs and CD95 agonistic
      antibody in the induction of apoptosis in MCF-7 cells. In summary, our data
      indicate that drug-induced apoptosis of breast tumor cells occurs by a CD95/CD95L
      independent mechanism although by elevating the tumor suppressor proteins p53 and
      CD95, genotoxic drugs may sensitize breast tumor cells to CD95-mediated
      apoptosis.

PMID- 10200579
TI  - Activation of a low pH-dependent nuclease by apoptotic agents.
AB  - Intracellular acidification caused by agents such as UV(C), etoposide or ceramide
      accompanies the progression of apoptosis. It is suggested that cellular acidosis
      may set favorable conditions for a dormant, low pH-dependent (acidic) nuclease,
      which could be involved in intranucleosomal genome degradation, a hallmark of
      programmed cell death. Here we show that exposure of HL-60 cells to
      acidotic/apoptotic agents results in the several-fold activation of a novel low
      pH-dependent (acidic) nuclease activity, as revealed by zymography. Its activity,
      which resides in nuclei, is associated with four polypeptides with apparent Mr of
      56, 48, 45 and 40 kDa. Treatment of HeLa cells with UV(C) or ceramide causes also
      the up-regulation of an acidic nuclease activity which is represented by 70 and
      62 kDa polypeptides. These observations suggest that acidic nuclease activation
      can be induced by the same apoptotic agents in different cell types. In HL-60
      cells, acidic nuclease up-regulation triggered by acidotic agents follows the
      induction of AP-1 transcription factor active complexes and accompanies the
      progression of apoptosis. Inhibition of AP-1 factor activity caused by either
      anti-caspase/anti-acidotic agent Zn2+ or curcumin, an inhibitor of AP-1 binding
      to DNA and c-jun synthesis, protects cells from genome destruction. Acidic
      nuclease activation, however, is only partially inhibited by these factors. We
      propose that (i) the up-regulation of an acidic nuclease activity is governed by
      a regulatory pathway different from that responsible for AP-1 factor induction,
      caspases activation and intracellular acidification, and (ii) activation of an
      acidic nuclease does not cause any deleterious effects when AP-1 transcription
      factor induction, caspases activation and intracellular acidification are down
      regulated. Thus, the acidic nuclease up-regulation alone is not a sufficient
      prerequisite for apoptosis.

PMID- 10200580
TI  - Role of PI3-kinase in Bcl-X induction and apoptosis inhibition mediated by IL-3
      or IGF-1 in Baf-3 cells.
AB  - In Baf-3 cells, IL-3 and IGF-1 both inhibit cell death. These growth factors act
      at least on two different pathways involved in the inhibition of apoptosis. They
      both upregulate Bcl-X at the mRNA and protein levels and also activate a pathway
      which inhibits apoptosis in the absence of protein synthesis. Recently, these two
      growth factors have been shown to activate the PI3-kinase-AKT pathway which leads
      to the phosphorylation of the pro-apoptotic Bcl-XL regulator Bad. In this study,
      we have investigated the role of PI3-kinase in the regulation of Bcl-X expression
      and in the survival of Baf-3 cells. We show that PI3-kinase activation is
      involved in the upregulation of Bcl-X mRNA induced by both IL-3 and IGF-1.
      Moreover, PI3-kinase activity is also necessary for inhibition of apoptosis and
      caspase regulation by IGF-1 but not IL-3.

PMID- 10200581
TI  - The First European Workshop on Cell Death: (Death on the Rocks) held at Gran
      Sasso, Italy, 21 - 25 October 1998. Rocking cell death.

PMID- 10200582
TI  - Lymphocyte subsets in renal transplant recipients during growth hormone therapy.
AB  - OBJECTIVE: To evaluate the effect of growth hormone treatment on growth, levels
      of insulin-like growth factor I (IGF-I) and lymphocyte subsets in
      immunosuppressed renal allograft recipients. METHODS: 18 children (aged 8.0-16.6
      years) received growth hormone 1 IU/Kg/week daily for two years. Height, IGF-I
      levels and in 11/18 patients, lymphocyte subsets were evaluated serially.
      RESULTS: Standardized growth velocity increased from -1.0+1.5 to +1.2+2.2 and
      standardized IGF-I levels from +0.8+1.5 to +3.1+1.1 (1 year) and to +1.4+1.7 (2
      years). The total lymphocyte count and the number of T lymphocytes (CD3+)
      decreased. The decrease was more marked in CD8+ (from 1.5+0.3 x10(9)/L to 0.9+0.3
      x10(9)/L, 1 year and to 0.8+0.1 x10(9)/L, 2 years) compared to CD4+ (from 1.5+0.3
      x10(9)/L to 1.0+0.2 x10(9)/L, 1 year and to 1.3+0.2 x10(9)/L, 2 years), resulting
      in an increment of the CD4+/CD8+ index. CONCLUSIONS: The differential effect of
      growth hormone treatment on CD4+ and CD8+ lymphocytes might be explained by
      different expression of the IGF-I receptor in these distinct subsets.

PMID- 10200583
TI  - Thyroid volume, urinary and milk iodine in mothers after delivery and their
      newborns in iodine-replete country.
AB  - OBJECTIVE: To estimate thyroid volume (ThV) in primiparous (PP) and multiparous
      (MP) mothers (MO) and their newborns (NB) as related to their urinary iodine and
      thus contribute to the question on the interrelation between iodine intake during
      the pregnancy and thyroid function in pregnant women. METHODS: The ThV by
      ultrasound was estimated in a total of 258 MO (108 PP and 150 MP)) and their
      newborns on the 4th-7th day after delivery. There were 227 in term and 31 preterm
      (before 37th week) deliveries. In addition, ThV was estimated in double amount of
      controls (216 vs. PP and 300 vs. MP) in the same age range and nearly age matched
      which were either nulliparous or did not have delivery within last 12 months.
      Urinary iodine concentration was estimated in spot urine samples obtained from 75
      MO and their NB and milk iodine in 44 milk samples obtained between the 4th and
      7th day after delivery. RESULTS: On the first week after delivery, the ThV in all
      258 MO was significantly higher than that in 516 of nearly age matched females
      (mean+S.D.: 14.87+4. 93 ml vs. 10.61+4.02 ml, resp., P<0.01). Although the ThV
      was lower in 108 PP than in 150 MP women (mean+S.D.: 13.85+4.51 ml vs. 15.59+5.
      11 ml, resp., P<0.01), it was still significantly higher (P<0.01) than that in a
      double amount of nearly age matched controls for PP (9.96+3.15 ml) and MP
      (11.07+4.48 ml). Mean ThV found in all 258 NB was 0.60+0.21 ml (median 0.5 ml,
      range 0.2-1.6 ml), the values in those born in term being higher than in preterms
      (mean+S.D. 0.62+0. 20 ml vs. 0.45+0.12 ml; P<0.01). No correlation was found
      between the ThV and body weight in NB. However, significant correlation was found
      between the ThV in all 257 NO and their NB (r=0.292, P<0.05). The mean value of
      urinary iodine in mothers on the first week after delivery was 9.0+7.2 ug/dl
      (median 6.1, range 3.0-47.2). The average urinary iodine in primiparous was
      slightly higher than that in multiparous mothers (10.3 vs. 8.4 ug/dl; not
      significant). In newborns, the mean urinary iodine in the first week after birth
      was 11.6+7.6 ug/dl (median 6.5, range 0.745.0). CONCLUSIONS: The finding of about
      30 % higher ThV in 258 mothers after delivery than that in double amount of
      nearly age matched women (P<0.01) who were either nulliparous or did not have
      delivery at least within last 12 months shows that, in spite of general
      satisfactory iodine intake in Slovak population, the iodine intake during
      pregnancy was not satisfactory. This is supported by the data on urinary iodine
      which was higher in primiparous than in multiparous women.

PMID- 10200584
TI  - Thymidine kinase activity in homogenates of rat thyroid lobes from euthyroid,
      hypothyroid and/or hyperthyroid rats incubated with EGF: studies ex vivo in
      vitro.
AB  - OBJECTIVE: To examine thymidine kinase (TK - ATP: thymidine 5'
      phosphotransferase, EC 2.7.1.21) activity in homogenates of rat thyroid lobes
      incubated in vitro with epidermal growth factor (EGF). METHODS: The thyroid lobes
      were collected from euthyroid, hypothyroid and/or hyperthyroid animals.
      Hypothyroidism was developed in the experimental rats by an administration of 0.1
      % solution of propylthiouracil (PTU) in drinking water for 2 weeks, while
      hyperthyroidism was obtained by daily i.p. injections of L-thyroxine (50
      microg/kg, B.W.), also for 2 weeks. After collecting, the thyroids were incubated
      for 4 hours in RPMI 1640 medium with an addition of 20 mM of Hepes buffer, 15%
      FCS, penicillin (200 U/ml), streptomycin (10 ug/ml) and with EGF (Sigma) (0.1
      ng/ml, 10 ng/ml, 1000 ng/ml). The control lobes were incubated without any
      addition of EGF to the medium. TK activity was expressed as the amount of
      reaction products, measured by ascending chromatography. RESULTS: 1. in the
      absence of EGF, TK activity in the homogenates of thyroid lobes from hypothyroid
      rats was lower, while it was higher in the lobes from hyperthyroid animals, when
      compared to these obtained from euthyroid controls; 2. EGF in the concentration
      of 0.1 ng/ml or 1000 ng/ml decreased, while that in the concentration of 10 ng/ml
      increased TK activity in lobes collected from euthyroid or hyperthyroid rats; 3.
      in the tissue collected from hypothyroid rats, the addition of EGF (0.1 ng/ml or
      10 ng/ml) caused a slight increase in TK activity versus hypothyroid controls - a
      tendency towards diminishing TK activity could be observed as parallel to
      increasing EGF concentration. CONCLUSIONS: TK activity in the homogenates of rat
      thyroid lobes depends on the functional thyroid status and on applied EGF
      concentration in vitro.

PMID- 10200585
TI  - Overweight and increased diabetes susceptibility in neonatally insulin-treated
      adult rats.
AB  - OBJECTIVE: Since the offspring of gestational diabetic mothers (GD) is at
      increased risk to develop obesity and diabetogenic disturbances later in life,
      while pathophysiological mechanisms responsible are unclear, to investigate long
      term consequences of neonatal hyperinsulinism occurring characteristically in GD
      offspring. METHODS: Newborn Wistar rats received daily subcutaneous injections of
      a long-acting insulin from the 8th to 11th day of life (IRI), while in controls
      (CO) NaCl was applied. Body weight was recorded throughout life. Glucose
      tolerance test was performed on the 140th day of life (1.5 g/kg glucose injected
      i.p. after an overnight fast and blood samples were taken up to 90 min from
      retroorbital plexus). On the 240th day of life, the vulnerability to a single
      "subdiabetogenic" dose of streptozotocin (STZ; 25 mg/kg body weight) was tested.
      Blood samples for estimating glucose levels were taken before STZ, and
      subsequently on days 2, 7, 14, 21, and 28 after STZ. RESULTS: IRI rats developed
      overweight during juvenile life until adulthood (P<0.001), characterized by a
      clear elevation of the Lee obesity index (P<0.005), and associated with basal
      hyperglycaemia (P<0.05), hyperinsulinaemia (P<0.05), as well as an increased
      insulin/glucose-ratio as a measure of insulin resistance (P<0.005). Impaired
      glucose tolerance occurred in early adulthood, and increased vulnerability to a
      "subdiabetogenic" dose of streptozotocin (see above), leading to significant
      hyperglycaemia (P<0.05), was evaluated in the 9th month of age. Accompanied by a
      transient reduction of hyperinsulinaemia during a period of 21 days, Lee obesity
      index and insulin/glucose-ratio decreased significantly after STZ treatment in
      IRI rats (P<0.01). CONCLUSIONS: Overweight and increased diabetes susceptibility
      in adulthood due to temporary hyperinsulinism during a critical period of
      postnatal life are suggested to be a consequence of acquired dysregulation and
      overstimulation, respectively, of the pancreatic insulin secretion in rats.

PMID- 10200586
TI  - Porcine granulosa cells produce a progesterone secretion inhibitory activity.
AB  - OBJECTIVE: To extend our previous observations of granulosa cell conditioned
      medium inhibition on basal and FSH-stimulated progesterone secretion by granulosa
      cells from large porcine antral follicles. METHODS: Granulosa cell conditioned
      media (SGCCM) were obtained from cultures of granulosa cells which were harvested
      from small porcine antral follicles. SGCCM were fractionated by filtration
      through an Amicon XM-50 and an PM-10 membrane. RESULTS: Two fractions - XM-50
      filtrate (<50 kDa) and PM-10 retentate (10-50 kDa) - exhibited well expressed
      inhibitory effect on the progesterone secretion from large follicle granulosa
      cells in vitro. Such inhibitory effect was fully prevented by heat treatment,
      partially inactivated by trypsin digestion (P<0.05), but was resistant to several
      freeze-thaw cycles and storage at -20 or -70 degrees C for up to one year.
      CONCLUSIONS: It is suggested that SGCCM contains some regulatory substance(s)
      capable of inhibiting progesterone secretion by cultured granulosa cells and that
      the molecular weight of such substance is presumably between 10-50 kDa.

PMID- 10200587
TI  - Minireview: discussion about the limit between normal thyroid goiter.
AB  - Although the goitre seems to be well defined at least from clinical point of
      view, it is virtually impossible to find the precise definition of the opposite
      side of what should be the normal thyroid as concerns its size, histological
      structure and namely the level of growth stimulation by the external factors
      (such as TSH) and intrinsic tissue growth factors. Theoretically, the normal
      thyroid should be able to cover the requirements of the organism for the hormone
      in a reasonably large range without being stimulated to grow by any external or
      internal factors. So far, the search for normal thyroid has been conducted by
      several ways: 1. by post mortem thyroid weight, 2. by palpation, 3. by
      ultrasound. As based on post mortem thyroid weight, until the middle of this
      century a typical thyroid gland was considered to be about 20-25 g with the
      accepted upper normal size of 30 g, while more recent studies in iodine replete
      population have reported mean weights of about 10 g and an upper normal size 20
      g. According to several classifications for thyroid palpation the unpalpable
      thyroid should be allotted to the Grade 0 which is defined as "normal gland", "no
      goiter at all", "absence of goiter" etc. The first recommendation of normal
      thyroid volume for children and adolescents as estimated by ultrasound has been
      developed by Gutekunst and Teichert (1994). However, this was later challenged by
      the findings of considerable number of thyroid volumes which were higher than the
      upper limit of that recommendation as found in the countries with satisfactory
      values of urinary iodine (Delange et al. 1997). Nevertheless, recently it
      appeared that about 10-15 percent of adolescent thyroids show increased thyroid
      growth rate which significantly differs from the majority and which might be
      related to different tuning of molecular growth mechanism presumably of genetic
      origin (Tajtakova et al. 1998; Langer et al., in press). From, this follows that
      a certain number of enlarged thyroids apparently should not be included into a
      normal range.

PMID- 10200588
TI  - Circadian variations of androstenedione, dehydroepiandrosterone sulfate and free
      testosterone in obese women with menstrual disturbances.
AB  - OBJECTIVE: To assess the 24 h profile of androgenemia related to the androgens of
      both the ovarian and adrenal origin in obese women with menstrual disturbances.
      METHODS: The association of body mass and body fat distribution with circadian
      variations of selected androgens of ovarian and adrenal origin was examined in 16
      obese women with menstrual disturbances (BMI between 38 and 51 kg/m2; WHR between
      0.80 and 0.99) and in 16 healthy volunteers with normal body weight (BMI between
      21 and 24.6 kg/m2; WHR between 0.73 and 0.76). The age range of all subjects was
      29 to 40 (mean: 36.9+/-3.2 years). RESULTS: lts. Both the patients and control
      subjects showed a significant 24 h rhythm of androstenedione (A) and free
      testosterone (FT), while the circadian oscillations of dehydroepiandrosterone
      sulphate (DHEAS) did not differ significantly. In all obese women mean 24 h A,
      DHEAS and FT levels were significantly higher than those in controls. Moreover,
      the disturbances of DHEAS and FT secretion in the form of acrophase shift (for
      DHEAS from 7.37 to 3.45 h and for FT from 6.04 to 3.31 h) and the elevation of
      their 24 h amplitude values were observed. All obese women showed higher values
      of FT/A and FT/DHEAS indexes in selected clock time of day/night cycle (except
      those at 8.00 h for FT/A and at 5.00 h for FT/DHEAS) when compared to control
      group. A positive correlation was noted in all women studied between the values
      of BMI index, WHR ratio and mean 24 h level of androgens studied as well as FT/A
      and FT/ DHEAS indexes. A weaker correlation was found between body mass and body
      fat distribution on the one hand and fasting level of hormones studied on the
      other. Higher correlation between the values of WHR ratio and mean 24 h FT levels
      as well as FT/DHEAS indexes were obtained in obese women when compared to those
      of healthy subjects. CONCLUSIONS: Our findings suggest that, when assessing the
      androgen disturbances in obese patients, it is more useful to determine their
      circadian pattern than the basal level. The most reliable indicators of
      hyperandrogenism in obese women are: the 24 h concentration profile of FT and the
      value of FT/DHEAS index, not only during fasting but also after a meal at various
      time intervals. Circadian FT concentration and FT/DHEAS index values are
      essential indicators for visceral distribution of adipose tissue.

PMID- 10200589
TI  - Assessment of bone metabolism in obese women.
AB  - OBJECTIVE: To evaluate the bone metabolism in obese women by the estimation of
      selected markers of bone formation. METHODS: The concentration of plasma
      parathyroid hormone (PTH) and selected markers of bone formation [osteocalcin
      (BGP) in plasma, carboxyterminal propeptide of type I procollagen (PICP) and
      alkaline phosphatase (AP) activity in blood serum] and bone resorption [cross
      linked carboxyterminal telopeptide of type I collagen (ICTP) in blood serum and
      urinary excretion of calcium (Ca)] in 18 extremely obese women (BMI>40 kg/m2)
      with android phenotype (WHR>0.8) and in 20 healthy women with normal body weight.
      The age range of all subjects was 25 to 42 years (mean: 36.82 + 3.95). RESULTS:
      All obese women showed significantly increased concentration of plasma PTH, BGP
      and serum PICP, ICTP and elevated urinary excretion of Ca. CONCLUSIONS: The
      obtained results show that in extremely obese women with android phenotype bone
      metabolism disturbances may occur pointing at increased bone formation and
      resorption.

PMID- 10200590
TI  - The effects of Soybean Diet on Thyroid Hormone and Thyrotropin Levels in Aging
      Rats.
AB  - OBJECTIVE: To estimate the effect of soybean diet on serum level of thyroid
      hormone, its metabolites and thyrotropin (TSH) during aging in rats. METHODS:
      Male Donryu rats were fed laboratory chow containing 40 (Group A) or 10 volume
      percent (Group B) soybean protein, while controls (Group C) received regular
      laboratory chow. Groups of 10 animals of each groups were sacrificed by
      decapitation at the age of 12, 18, 24 and 30 months. Serum total thyroxine (T4),
      free thyroxine (FT4), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine
      (rT3) and 3,3'-diiodothyronine (3,3'-T2) and TSH concentrations were measured by
      specific radioimmunoassays. RESULTS: In Group A the level of T3 decreased
      significantly at from the age of 18 months, while in other groups such decrease
      was found only from the age of 24 months. Such changes were closely resembled by
      these in the level of 3,3'-T2, while inverse changes were observed in the level
      of rT3 which was increased in Group A from the age of 18 months and in the other
      groups from the age of 24 months. Serum T4 and FT4 level was decreased in all
      groups at the age of 30 months and no changes were observed in the level of TSH.
      CONCLUSIONS: The findings suggest that the level of T4, FT4 and T3 with its
      metabolite 3,3'-T2 stepwise decreased with aging, while that of rT3 showed
      inversely and increase. These changes were influenced by the content of soybean
      protein in the diet, the most rapid changes being found in the group with the
      high content of such protein.

PMID- 10200592
TI  - Minireview: Polychlorinated Biphenyls and the Thyroid Gland.

PMID- 10200591
TI  - Accuracy and Significance of Fine-Needle Aspiration Cytology and Frozen Section
      in Thyroid Surgery.
AB  - OBJECTIVE: In the retrospective study to review the records of patients who had
      undergone thyroid surgery between 1986-1995 and to determine the need of frozen
      section (FS) following FNA biopsy. METHODS: The records of 2083 patients who had
      thyroid surgery in Gazi University Medical Faculty Department of General Surgery
      between 1986-1995 were retrospectively reviewed to determine and compare the
      accuracy and significance of fine-needle aspiration (FNA) cytology and
      intraoperative frozen section (FS). Results. In 61 patients, both FNA and FS
      diagnosis were available for the comparison with the final pathologic diagnosis.
      In 196 patients, FNA diagnosis was available for the comparison with the final
      pathological diagnosis by permanent section and in 377 patients FS diagnosis was
      available for the comparison with the final pathological diagnosis. The
      sensitivity value for detection of malignancy by means of FNA was 57.1 % compared
      to 82.2 % by means of FS, and FS diagnosis was more specific (99 %) than FNA
      diagnosis (90.9 %). FNA diagnosis of benign conditions was correct in 141 of 150
      (94 %) patients. FS diagnosis of benign conditions was correct in 313 of 321
      (97.5 %) patients. Nine patients had the FNA findings that were positive for
      malignancy and FS confirmed this diagnosis in 8 patients. Conclusions. FNA is an
      important diagnostic tool for eliminating benign nodules, but it is not perfect.
      FS is very important for determining the surgical procedure, and because of
      direct observation of suspicious nodule, it is even more accurate. Using these
      tools together is more reliable, since the number of false positive and false
      negative values is lower than if only the individuals methods are used.

PMID- 10200593
TI  - The endless tragedy of pediatric AIDS.

PMID- 10200594
TI  - Fifty years: advancing knowledge, improving health.

PMID- 10200595
TI  - A personal perspective on HIV-AIDS research.

PMID- 10200596
TI  - Unique properties of a second human herpesvirus 8-encoded interferon regulatory
      factor (vIRF-2).
AB  - OBJECTIVE: Human herpesvirus 8/Kaposi's sarcoma herpesvirus (HHV-8/KSHV)
      contains, in addition to genes required for viral replication, an unique set of
      nonstructural genes which may be part of viral mimicry and contribute to viral
      replication and pathogenesis in vivo. Among these, HHV-8 encodes four open
      reading frames (ORFs) that show homology to the transcription factors of the
      interferon regulatory factor (IRF) family. In this study we demonstrate that one
      of these ORFs (vIRF-2) encodes a protein with mobility of 18 kd which has
      distinct pattern of expression and properties from the cellular IRFs and the
      previously characterized vIRF-1. METHODS: We cloned vIRF-2 by polymerase chain
      reaction (PCR) and studied its expression by Northern blot and reverse
      transcription-polymerase chain reaction (RT-PCR). Biologic activities were tested
      by chloramphenicol acetyltransferase (CAT) assay in transiently transfected
      mammalian cells. We characterized its DNA binding specificity by electrophoretic
      mobility shift analysis (EMSA) and its protein-protein interactions by in vitro
      pull-down assay. RESULTS: Although low levels of vIRF-2 mRNAs can be detected in
      the HHV-8-positive BCBL-1 tumor cell line, 12-0-tetradecanoylphorbol-13-acetate
      (TPA) treatment does not stimulate expression of vIRF-2 gene together with
      primary lytic cycle genes. Recombinant vIRF-2, which can form homodimers, does
      not bind specifically to the oligodeoxynucleotide repeats corresponding to the
      interferon-stimulated response element (ISRE), but it does bind to the NF-kappa B
      binding site. The fusion protein generated from vIRF-2 and the RelA (p65)
      activation domain stimulates transcriptional activity of HIV LTR, which contains
      two NF-kappa B sites, but does not stimulate the interferon-beta (IFNB) promoter,
      which contains only one NF-kappa B site. Interaction between recombinant vIRF-2
      and cellular IRFs such as IRF-1, IRF-2, and ICSBP was detected by in vitro
      binding assay, but no interaction between IRF-3 and vIRF-2 was found. Interaction
      of vIRF-2 with RelA (p65) and the carboxy-terminal part of p300 was also
      observed. In a transient transfection assay, vIRF-2 inhibits the IRF-1- or IRF-3
      mediated transcriptional activation of interferon-alpha (IFNA) gene promoter in
      infected cells and downmodulates RelA (p65)-stimulated activity of HIV LTR.
      CONCLUSIONS: These results suggest that, by interacting with cellular
      transcription factors and cofactors, vIRF-2 may modulate the expression of the
      early inflammatory genes and potentially deregulate the immune system.

PMID- 10200597
TI  - Epstein-Barr virus-encoded nuclear protein EBNA-3 interacts with the epsilon
      subunit of the T-complex protein 1 chaperonin complex.
AB  - OBJECTIVE: To find cellular proteins that associate with EBNA-3 (also called EBNA
      3A), one of the Epstein-Barr virus (EBV)-encoded growth transformation-associated
      nuclear proteins. METHODS: Screening human cDNA libraries in the yeast two-hybrid
      system and performing an analysis of interaction in vitro as well as in cell
      lysates. RESULTS: EBNA-3 binds to the epsilon subunit of the chaperonin
      containing T-complex protein 1 (epsilon-TCP-1) in the yeast two-hybrid system.
      The cDNA clone isolated from a human lymphocyte library was found to encode the
      middle and C-terminal part of epsilon-TCP-1. The interaction was confirmed by
      showing that a GST fusion protein specifically precipitated EBNA-3 from CV1 cells
      infected with recombinant vaccinia virus expressing EBNA-3. The interacting
      region was mapped to the putative apical domain of epsilon-TCP-1. CONCLUSIONS:
      This study shows that large, virus-encoded transforming proteins such as EBNA-3
      may receive help for their initial folding by chaperonin complexes. The
      recognition of the chaperonin complex likely occurs through specific interaction
      with one of the subunits. We suggest that nascent EBNA-3 may recognize the TCP-1
      complex by interacting with the apical region of the epsilon subunit.

PMID- 10200599
TI  - Relation between HIV-2 proviral load and CD4+ lymphocyte count differs in
      monotypic and dual HIV infections.
AB  - OBJECTIVE: To explore and compare the relations between proviral DNA load and
      CD4+ lymphocyte counts in both HIV-2 monotypic and HIV dual infection. STUDY
      DESIGN/METHODS: In Dakar, Senegal, where the HIV-1 and HIV-2 epidemics overlap,
      serum and peripheral blood mononuclear cell (PBMC) DNA samples were collected
      from registered female sex workers and hospitalized patients. Sera were evaluated
      for reactivity to antigens of HIV-1 and HIV-2 by immunoblot; dual reactivity was
      confirmed with recombinant envelope peptides for HIV-1 and HIV-2. These samples
      were then subjected to HIV-1 and HIV-2 proviral DNA polymerase chain reaction
      (PCR). To evaluate the HIV-2 cellular proviral DNA loads, a quantitative
      competitive PCR (QC-PCR) was developed using nested primers to amplify the gag
      region of HIV-2. This assay used an internal competitor generated by inserting 25
      bp in the first-round PCR target sequence. T-lymphocyte subset counts were
      estimated by flow cytometry for both HIV-2 monotypic and dually infected persons.
      RESULTS: 35 HIV-2-infected and 33 dually seroreactive samples were evaluated in
      this study. The CD4+ lymphocyte counts were similar in both groups, with mean
      values of 449 +/- 390 cells/mm3 for the HIV-2 monotypic infected persons and 476
      +/- 308 cells/mm3 among the dually infected persons. However, the median proviral
      loads differed significantly, with those in the HIV-2 group ranging from 63.2 to
      669.8 copies/10(5) CD4+ cells and demonstrating an inverse correlation with CD4+
      lymphocyte count. The HIV dually infected persons showed less variation in viral
      load, ranging from 9.9 to 43.3 copies/10(5) CD4+ cells. Among the HIV dually
      infected persons, low HIV-2 proviral load was correlated with low CD4+ lymphocyte
      counts. CONCLUSIONS: The HIV-2 proviral loads in HIV dually infected persons were
      significantly lower than those in HIV-2 monotypically infected individuals (P <
      .0001), despite comparable CD4+ lymphocyte counts. These results suggest that
      different HIV-2 proviral dynamics prevail in HIV dual infection.

PMID- 10200598
TI  - Cellular localization of human herpesvirus 8 in nonneoplastic lymphadenopathies
      and chronic interstitial pneumonitis by in situ polymerase chain reaction
      studies.
AB  - OBJECTIVES: To study the cellular localization of human herpesvirus 8 (HHV-8) in
      rare cases of HHV-8 infection from Italy that are associated neither with human
      immunodeficiency virus (HIV) infection nor Kaposi's sarcoma (KS). METHODS: The
      presence and distribution of HHV-8-infected cells was investigated by direct in
      situ polymerase chain reaction (PCR) in the lymph node tissues from 2 patients
      with reactive lymphadenopathies with florid follicular hyperplasia and increased
      vascularity and in the lung tissue from 1 patient with chronic interstitial
      pneumonitis. RESULTS: HHV-8 was localized in lymphoid and monocyte-macrophage
      cells scattered in the interfollicular regions of both lymph nodes but not in
      endothelial cells. In the lung tissue, HHV-8 was found in the inflammatory cells
      infiltrating the interalveolar interstitium, in endothelial cells of the
      pulmonary vasculature, and in rare pneumocytes. CONCLUSIONS: HHV-8 can infect
      nonneoplastic lymph nodes of immunocompetent subjects, and the distribution of
      infected cells outside of the germinal centers resembles that of Epstein-Barr
      virus (EBV)-infected cells in the lymph nodes in the course of infectious
      mononucleosis. Endothelial cells and pneumocytes may be a target of HHV-8
      infection out of the KS setting, at least in the presence of a chronic
      inflammatory process.

PMID- 10200600
TI  - Changes in circulating levels of HIV, CD4, and tissue expression of HIV in a
      patient with recent-onset ulcerative colitis treated by surgery. Case report.
AB  - OBJECTIVE: To determine CD4+ T-cell count and circulating and tissue levels of
      HIV before and after surgery in a patient with recent-onset ulcerative colitis.
      STUDY DESIGN/METHODS: CD4 lymphocytes and circulating and tissue HIV RNA levels
      were measured in an HIV-infected patient with ulcerative colitis before and after
      proctocolectomy. RESULTS: Approximately 3 weeks prior to surgery for ulcerative
      colitis that was unresponsive to corticosteroids, the patient's CD4 count was 930
      cells/mm3 and fell to 313 cells/mm3 within 10 days; the viral burden was
      approximately 80,000 RNA copies/mL. Tissue macrophages and lymphocytes in biopsy
      and resection specimens were shown to express high levels of HIV RNA by in situ
      hybridization. Five days postoperatively, the patient became asymptomatic and was
      discharged on tapering prednisone without antiretroviral agents. After surgery,
      the patient's CD4 count progressively rose, while viral RNA levels precipitously
      dropped. At 3, 6, and 15 weeks postoperatively, CD4 and viral RNA counts were 622
      cells/mm3 and 31,300 RNA copies/mL, 843 cells/mm3 and 11,400 RNA copies/mL, and
      747 cells/mm3 and 1500 RNA copies/mL, respectively. CONCLUSIONS: Circulating
      levels of HIV and CD4+ cells, as well as tissue expression of HIV, apparently can
      be influenced by localized inflammatory processes such as those occurring in
      inflammatory bowel disease.

PMID- 10200601
TI  - HIV vaccines and prevention in a world without Mary Lou Clements-Mann and
      Jonathan Mann.

PMID- 10200603
TI  - [Physiological function of BCL-3].

PMID- 10200602
TI  - [Molecular functions of cofilin which regulates reorganization of actin
      cytoskeleton].

PMID- 10200604
TI  - [Recent advances in the gene chip and its role in the post-genome era].

PMID- 10200605
TI  - [A novel plant lectin group has homologous structure to ribosome-inactivating
      protein, ricin].

PMID- 10200606
TI  - [Cellular signal transduction via the neurofibromatosis type 2 tumor suppressor
      gene product; merlin].

PMID- 10200607
TI  - [Characterization of protein isoaspartyl methyltransferase (PIMT)-deficient
      mice].

PMID- 10200608
TI  - [Integrin signal transduction via FAK in osteoblasts--early differentiation
      triggered by osteopontin].

PMID- 10200609
TI  - [Abolishment of the profession of barber-surgeon. Causes, circumstances and
      effects demonstrated on the example of the Kingdom of Wurttemberg (1886-1918)].

PMID- 10200610
TI  - [Chronic viral hepatitis--diagnosis, therapy and prognosis].
AB  - Infections with the hepatitis B, C or D virus can all lead to chronic hepatitis.
      Serological and molecular methods are essential for diagnosis and for
      differentiation between the different forms of chronic virus hepatitis. In adults
      between 5 and 10% of all infections with the hepatitis B virus become chronic
      while the rate is as high as 80% with the hepatitis C virus. All forms of chronic
      hepatitis are frequently asymptomatic for a long period of time. Complications
      are liver cirrhosis and hepatocellular carcinoma. During chronic hepatitis B
      infection in around 1% of the patients per year the virus is eliminated
      spontaneously while virus elimination occurs rarely in patients with chronic
      hepatitis C infection. In patients with chronic hepatitis C infection over a
      period of 30 years around 3% of the patients die due to chronic hepatitis C
      infection. As soon as chronic virus hepatitis is diagnosed treatment should be
      considered. Standard therapy for all forms of chronic viral hepatitis is
      interferon alpha. Additionally recent results indicate that nucleoside analogous
      are effective for chronic hepatitis B and C virus infection. For chronic
      hepatitis B infection studies with famciclovir and lamivudine show that viral
      replication can be effectively blocked. For chronic hepatitis C infection a
      combination therapy with interferon and ribavirin has been shown to reach higher
      elimination rates compared to interferon mono-therapy. The last treatment option
      for all forms of viral hepatitis is liver transplantation.

PMID- 10200611
TI  - [Atherosclerosis--a chronic infectious disease caused by Chlamydia pneumoniae].
AB  - Recent investigations allow a controversial but convincing interpretation of the
      pathogenesis of atherosclerosis (arteriosclerosis). Atherosclerosis can be
      apparently the result of ultrachronic persistent infection by Chlamydia
      pneumoniae and not the result of heterogenous risk factors. The main arguments
      for the chlamydial genesis are: Correlation of coronary heart disease and other
      atherosclerotic diseases and antibodies against Chlamydia pneumoniae. Chlamydia
      pneumoniae could be detected with different techniques (PCR, ICC,
      immunohistology, electromicroscopy, culture) in a high percentage in atheromas
      from different sites. Three successful international studies with macrolides in
      coronary heart disease. Target cells of atherosclerosis (endothelia, macrophages,
      muscle cells) can be infected by Chlamydia pneumoniae in vitro. Provocation of an
      arteriitis in animal experiments. The reduction of incidence of atherosclerotic
      diseases since the 1960s, probably due to advanced antibiotic therapy. Elevated
      acute-phase proteins and other inflammatory signs (CRP, WBC count, fibrinogen)
      briefly before occurrence of myocardial infarction. There are good arguments for
      intervention studies in coronary heart disease and other manifestations of
      atherosclerosis. The relevant antibiotics are licensed for chlamydial infections,
      cheap and safe. Meticulous records and long-term observation of patients need to
      be developed, sometimes contrary to interests of the pharmaceutical industry.

PMID- 10200612
TI  - [New trends in the follow-up of malignant diseases].
AB  - For many of the frequent malignant diseases (e.g. breast cancer, lung cancer,
      gastrointestinal cancers and urological cancers--except germ cell tumors) there
      is no clear evidence (in the sense of "evidence-based medicine") for the efficacy
      of fixed schedules during follow-up using imaging or laboratory procedures.
      Intensive and expensive follow-up programs could be justified by proven results,
      e.g. a better chance of cure, a longer survival and/or a better quality of life.
      But unfortunately, such results are not available for most of the frequent
      tumors. The following criteria should lead every physician when guiding his
      patients through the follow-up period after the potentially curative treatment of
      a malignant disease: Every single diagnostic step must be backboned by a clear
      medical rationale. Alone the fact that technical investigations can be made
      easily and are available almost everywhere cannot be the rationale to perform
      these methods routinely. The wish of the patient alone, to have some technical
      applications, is not a plausible reason to perform it, unless there is a clear
      medical indication. The unfounded and private desire of the physician, that he
      should know some results (e.g. tumor markers), is in most cases, insufficient
      justification.

PMID- 10200613
TI  - [The rehabilitation of older people].
AB  - Although age itself is not a disease, older people are more likely to contact
      diseases. These diseases and the loss of facilities in old age can develop slowly
      and almost unnoticed or can result from an acute illness. It is always important
      to intervene in good time as for older people spontaneous healing is often
      impossible without rehabilitation. This article deals with the development of
      geriatrics in Germany and introduces the institutions for geriatric
      rehabilitation. Taking the example of the geriatric department, it will describe
      in-patient and partial in-patient rehabilitation, the geriatric day clinic with
      out-patient rehabilitation and the rehabilitation team. The article ends by
      formulating some demands of governmental health policies and points out that
      nowadays the success of geriatric work is measurable.

PMID- 10200614
TI  - ["Self-inflicted injuries"--psychiatric, forensic and insurance aspects (II)].
AB  - German law distinguishes between attempted suicide which is not punishable and
      self-mutilation which is prohibited. This article describes the historical
      development of self-injurious behaviour, reviews the social, juridical, and
      ethical assessments of the past, and examines the statistical and biological
      results of current research. It relates observations from forensic medicine and
      psychiatry to specific clinical symptoms, toxicological circumstances, and social
      influences (stress incurred by everyday life, war, or imprisonment). Drawing on
      pertinent cases, it clarifies criminal and civil jurisdiction and emphasizes the
      importance of self-mutilation for private insurers. Intended for insurers,
      forensic scientists, and psychiatrists, recommendations concern the procedures to
      be followed in the examination, jurisdiction, and therapy involving cases of self
      inflicted injuries.

PMID- 10200615
TI  - [Is orlistat medically essential for the treatment of obesity?].
AB  - Obesity is a major health problem in western societies. The mainstay of therapy
      is behavioral modification. By inhibiting intestinal lipases orlistat modifies
      food composition. Thus, orlistat is a dietetic compound. Therefore, orlistat does
      not represent a medically necessary treatment option in terms of the conditions
      of private health insurances. However, adjunctive treatment with orlistat may
      make sense in single high risk patients.

PMID- 10200616
TI  - [19. ICLAM--International Congress for Medical Insurance].

PMID- 10200617
TI  - [Comment on N.-A. Sittaro: Risk assessment of expanded accident insurance for
      children. Versicherungsmedizin 50 (1998) Heft 4 S. 131].

PMID- 10200618
TI  - [Medical support for the Armed Forces: the results and the outlook].
AB  - A discussion of actual problems in the medical maintenance of the Armed Forces of
      Russia--combat and deployment readiness of the medical service, its personnel
      training programmes, sanitary-epidemiological control, medical treatment and
      prophylactics, medical materiel research and development for troops health care.
      The article deals with the military medical service' tasks of 1999 and of the
      imminent future focusing on the medical specialists' education with a due regard
      for their stationing and a possibility of substitution of military medical
      officers by civilians and the formation of an overall Armed Forces medical
      maintenance system on a territorial basis.

PMID- 10200619
TI  - [The clinico-epidemiological and medical expertise characteristics of
      neuropsychic morbidity in draftee contingents].
AB  - Official statistics show unfavourable growth tendencies of psychoneurological
      morbidity in younger generation in Russia, which creates recruitment problems for
      its Armed Forces. The authors offer a number of measures for preliminary checking
      up of the drafted personnel to prevent potential patients from joining the Army.

PMID- 10200620
TI  - [The methods of traditional medicine in outpatient polyclinic practice].
AB  - Some 7950 patients have been treated at the traditional medicine department of
      the Consulting and Diagnostic Center N52, 2/3rds of them came after long and
      unsuccessful medicamental treatment. Psychotherapy, manual therapy and
      acupuncture-reflex methods were successful in 86-93% of cases. They are
      recommended for local clinics provided that the latter are properly equipped and
      stuffed.

PMID- 10200621
TI  - [The use of simplified extrascleral alloscleroplasty in progressive myopia in
      servicemen].

PMID- 10200623
TI  - [The early diagnosis of the Marfan syndrome in servicemen].

PMID- 10200622
TI  - [The antibacterial therapy of community-acquired pneumonia].

PMID- 10200624
TI  - [A new Russian immunomodulating and anti-inflammatory preparation].

PMID- 10200625
TI  - [The trends in infectious morbidity in servicemen].
AB  - Analysing the morbidity situation in the Armed Forces the authors introduce the
      term "relative risk of morbidity ratio" as a means of calculation when comparing
      morbidity rates among military personnel and civilian population in a given
      district to formulate a morbidity rate forecast to help ships' or units' medics
      in preventive health care organisation.

PMID- 10200626
TI  - [The dynamics of the immunohematological indices in repeated exposures to radial
      accelerations].

PMID- 10200627
TI  - [The observation of legalities in the activities of the military medical
      service].

PMID- 10200628
TI  - [The organization of the delivery of surgical care in the Bundeswehr].

PMID- 10200629
TI  - [The development of clinical practice in the Military Medical Academy].

PMID- 10200632
TI  - Less is more (or how bigger is not necessarily better).

PMID- 10200631
TI  - Coding exams and radiographs.

PMID- 10200630
TI  - [The fate of Prof. V. A. Iurevich].

PMID- 10200633
TI  - How to profit from cosmetic dentistry. The case for case fees.

PMID- 10200634
TI  - How to profit from cosmetic dentistry. How the young dentist can profit.

PMID- 10200635
TI  - Initiate the transition to ... 'your opinion counts'.

PMID- 10200636
TI  - Funding your retirement.

PMID- 10200637
TI  - Infection control is more than just extra inventory.
AB  - Communication of infection-control practices is an overlooked area of practice
      management. Often, people forget to consider the training, time, and expense
      associated with the wide variety of protocols, techniques, and regimens. Explore
      and develop approaches aimed at conveying the infection-control practices you use
      to other care providers and your patient family. When these are used
      appropriately, you serve both patients and the community in the capacity for
      which you were trained--as a health-care professional. It does not get any better
      than that!

PMID- 10200638
TI  - Stamp out fear of rejection.

PMID- 10200639
TI  - Volatility in palladium market influences restorative dentistry.

PMID- 10200640
TI  - Is overhead bad?

PMID- 10200641
TI  - Where do these codes come from?

PMID- 10200642
TI  - How to profit from practice survey. The inside scoop on Dr. Typical.

PMID- 10200643
TI  - When 'someone else' messes up.

PMID- 10200644
TI  - DPMC. A force to be reckoned with.

PMID- 10200645
TI  - Are you healthy enough to provide health care?

PMID- 10200646
TI  - The dream team.

PMID- 10200647
TI  - Mastering customer service.

PMID- 10200648
TI  - Testifying.

PMID- 10200649
TI  - Going 'elective' in the family practice.

PMID- 10200650
TI  - The MSA option.

PMID- 10200651
TI  - Getting on e-mail lists.

PMID- 10200653
TI  - The learning of business.

PMID- 10200652
TI  - What a practice broker can do for you.

PMID- 10200654
TI  - High tech--an expense or an investment?

PMID- 10200655
TI  - Bonus systems: yes or no?

PMID- 10200656
TI  - Who can see your records?

PMID- 10200658
TI  - How to profit from Internet. A global study club.

PMID- 10200657
TI  - All smiles dental. Dental Practice of the Year.

PMID- 10200659
TI  - How to profit from Internet. Market your practice with attractive Web site.

PMID- 10200660
TI  - How to profit from Internet. A key to better practice management.

PMID- 10200661
TI  - How to profit from Internet. High time to order online.

PMID- 10200662
TI  - Selling to the financiers.

PMID- 10200664
TI  - Thieves you trust.

PMID- 10200663
TI  - A team's pride is sparked by 'input'.

PMID- 10200665
TI  - HIPPA's powerful suction.

PMID- 10200666
TI  - My name is John ... and I'm an alcoholic.

PMID- 10200668
TI  - The challenge is to climb a peak and cure a child's deformity.

PMID- 10200667
TI  - Huge group of dentists slandered?

PMID- 10200669
TI  - Why is the team unhappy?

PMID- 10200670
TI  - Many factors determine practice values.

PMID- 10200672
TI  - The shape of teeth to come.

PMID- 10200671
TI  - How to profit from photography. Technological explosion reinforces 'visual art'.

PMID- 10200673
TI  - A top 10 list of mistakes in practice management.

PMID- 10200674
TI  - Clearing the right jungle.

PMID- 10200676
TI  - The complaint box: who said, 'read 'em and weep?'.

PMID- 10200675
TI  - The millionaires club.

PMID- 10200677
TI  - From afar. 'Distance learning' closes the information gap by delivering it right
      into the practice.

PMID- 10200678
TI  - Dad's best lesson.

PMID- 10200679
TI  - Prototype your practice with a procedures manual.

PMID- 10200680
TI  - The Internet. Getting on e-mail lists.

PMID- 10200681
TI  - The devil in disguise!

PMID- 10200682
TI  - Losing our skilled providers.

PMID- 10200683
TI  - Why would anyone want to become a dentist?

PMID- 10200684
TI  - Do lasers deserve the 'flash in the pan' stigma? It depends on how diverse a
      practice is.

PMID- 10200685
TI  - Faster than an X-ray, safer than ... well, an X-ray.

PMID- 10200686
TI  - The specter of ... 'diagnosis paralysis'.

PMID- 10200687
TI  - Yesterday, insurance was such an easy game to play.

PMID- 10200688
TI  - Do we still need a boss on the assembly line in dentistry?

PMID- 10200689
TI  - A question about those connections.

PMID- 10200690
TI  - The best new patients may be looking for you!

PMID- 10200691
TI  - A five-step selling system.

PMID- 10200692
TI  - Tailor your practice to what the customer wants.

PMID- 10200693
TI  - The coalition forces.

PMID- 10200694
TI  - How to profit from computers. Intangible benefits of climbing new peaks.

PMID- 10200695
TI  - How to profit from computers. 10 rules for selecting a computer system.

PMID- 10200696
TI  - How to profit from computers. Wave of informatics will transform profession.

PMID- 10200697
TI  - DWI. Dental Wellness Index.

PMID- 10200698
TI  - A system that manages time.

PMID- 10200699
TI  - Why are you selling?

PMID- 10200700
TI  - Xylitol-based caries prevention: is there enough evidence for the existence of a
      specific xylitol effect?

PMID- 10200701
TI  - Tissue inhibitors of metalloproteinases level and collagenase activity in
      gingival crevicular fluid: the relevance to periodontal diseases.
AB  - OBJECTIVES: To provide an overall assessment of levels of tissue inhibitors of
      metalloproteinases (TIMPs), collagenase activities, and of immuno-reactivities
      for matrix metalloproteinases (MMP)-1 and -8 in gingival crevicular fluid (GCF)
      obtained from healthy subjects, and gingivitis and periodontitis patients, and to
      analyse the relationships between periodontal tissue destruction and the GCF
      components in periodontal diseases by principal component analysis. MATERIALS AND
      METHODS: GCF was sampled with sterile paper strips from 10 gingivitis and 11
      periodontitis patients. Ten volunteers served as clinically healthy controls.
      TIMP-1 and -2 protein amounts in GCF were measured by ELISA, and active and APMA
      activatable collagenase activities were determined by functional assays using
      image-analysis after SDS-PAGE. RESULTS: GCF TIMP-1 level and both active and
      latent collagenase activities were significantly higher in the diseased groups
      than in the healthy group. TIMP-2 was detectable in only 29% of all subjects
      (mean: 2.06 ng). Western blot analysis showed that MMP-8 was the major
      interstitial collagenase in the GCF of the diseased groups. Principal component
      analysis using clinical parameters and the GCF components has indicated
      components one to three account for 87% of total variation when evaluating the
      relevance of their measurements to periodontal diseases. CONCLUSIONS: We
      conducted the functional and immunological characterization of MMPs and TIMPs in
      the GCF of periodontally diseased patients. Principal component analysis
      indicated components one to three explaining 87% of total variation, and further
      suggested that higher collagenase activity (especially in active collagenase)
      would be an important marker in evaluating the pathogenesis of periodontitis.
      Consequently, these observations may have significant therapeutic and diagnostic
      implications.

PMID- 10200702
TI  - Hyaluronan and CD44 expression in minor salivary gland tumors.
AB  - OBJECTIVES: Hyaluronan (HA) and CD44 are most likely associated with tumor
      invasion and metastasis. Malignancies with different degrees of aggressiveness
      may express different levels and patterns of HA and CD44. The aim of this project
      was to examine the distribution of HA and CD44 in minor salivary gland tumors to
      determine if staining could be correlated with biologic behavior or tumor type.
      MATERIALS AND METHODS: Biotinylated hyaluronan binding protein as a probe for HA
      and monoclonal antibodies specific for CD44 were used to stain classic examples
      of the five most commonly encountered minor salivary gland tumors: monomorphic
      adenomas, pleomorphic adenomas, polymorphous low grade adenocarcinomas,
      mucoepidermoid carcinomas, and adenoid cystic carcinomas. RESULTS: Tumor cells of
      monomorphic adenomas were negative for both HA and CD44, and tumor capsules were
      intensely HA-positive. Pleomorphic adenomas exhibited HA and CD44 positivity in
      both mesenchymal and epithelial components, and HA in capsular tissues. All
      malignant salivary gland tumors expressed similar intense HA in tumor stroma. HA
      staining was more intense in stroma than in parenchymal cells. Tumor cells of
      most adenoid cystic carcinomas were HA-positive, while most polymorphous low
      grade adenocarcinomas were HA-negative. HA was uniformly distributed throughout
      supporting stroma of high and low grade malignancies, except for two polymorphous
      low grade adenocarcinomas (PLGAs) in which HA was more intense at the invading
      edge of the tumors. CD44 expression was seen only in tumor cells (not stroma) of
      malignancies, and was of similar intensity in both low and high grade tumors.
      CONCLUSIONS: Differences in the expression of HA and CD44 among different types
      of salivary gland tumors were noted. These findings, however, could not be
      correlated with known biologic behaviors of the tumor groups studied.
      Immunohistochemical staining of salivary gland tumors for HA and CD44 may be
      useful in separating monomorphic adenoma, polymorphous low grade adenocarcinoma
      and adenoid cystic carcinoma, lesions that may be difficult to distinguish with
      routine light microscopy.

PMID- 10200703
TI  - Alkalization produced by high-dose carbachol in HSG cell line is independent of
      Ca2+.
AB  - OBJECTIVES: The aim of this investigation was to clarify the mechanism of
      alkalization induced by carbachol in HSG cells. MATERIALS AND METHODS: Cells of
      the HSG cell line derived from a human submandibular gland adenocarcinoma and
      those of the A-431 human epidermoid carcinoma cell line were loaded with a
      fluorescent pH indicator, BCECF/AM, and the change in the intracellular pH of
      adherent cells and suspended ones were measured following stimulation with
      various concentrations (10(-7) M to 10(-2) M) of neurotransmitters (carbachol,
      noradrenaline, and isoproterenol). RESULTS: Isoproterenol did not cause
      alkalization of either cell type, whereas, noradrenaline and carbachol alkalized
      both types over the concentration ranges of 10(-6) M to 3 x 10(-3) M (HSG cell by
      noradrenaline), 10(-7) M to 2 x 10(-4) M (A-431 cell by noradrenaline), and 7 x
      10(-5) M to 10(-4) M (A-431 cell by carbachol). On the other hand, alkalization
      induced by carbachol in the HSG cells was recognized at concentrations higher
      than 6 x 10(-5) M, and it showed no upper limit in terms of carbachol
      concentration. This high-dose carbachol alkalization was not eliminated by
      preincubation with nifedipine (100 microM), a Ca2+ channel blocker, or with
      thapsigargin (100 microM), a microsomal Ca(2+)-ATPase inhibitor. CONCLUSIONS: The
      alkalization system induced by carbachol in the HSG cell was quite different from
      that in the A-431 cell, and that induced by high-dose carbachol in HSG cells
      appeared to be independent of intracellular Ca2+. These findings will be useful
      to clarify the mechanism of salivary secretion stimulated by neurotransmitters.

PMID- 10200704
TI  - Efficacy of topical mesalazine compared with clobetasol propionate in treatment
      of symptomatic oral lichen planus.
AB  - OBJECTIVE: To compare topically applied mesalazine (5-aminosalicylic acid) to
      topically applied clobetasol propionate in the treatment of patients suffering
      from symptomatic oral lichen planus. DESIGN: Randomized controlled longitudinal
      investigation. PATIENTS AND METHODS: Twenty-five out-patients suffering from oral
      lichen planus and referred to the Department of Oral Pathology and Oral Medicine
      of the University of Milan, Italy, during the period January to August 1997.
      Patients were randomly allocated (Group A and Group B) to treatment with
      mesalazine 5% or clobetasol propionate 0.05%. The drugs were topically applied
      twice daily for 4 weeks. Discomfort and pain were evaluated by the patient before
      and after treatment using a Visual Analogue Scale from zero (no pain) to 10
      (extreme pain). Results were statistically evaluated by a Mann-Whitney U test.
      RESULTS: The two pharmacological regimens obtained partial and complete absence
      of symptoms. In particular, the mesalazine tested group disclosed 57% complete
      absence of symptoms, 21.3% partial response and 9% no response. No statistically
      relevant difference has been detected between the two regimens. CONCLUSIONS: The
      results of this preliminary study, if confirmed by further investigations,
      suggest that mesalazine might be considered an alternative to clobetasol
      propionate for treatment of symptomatic oral lichen planus.

PMID- 10200705
TI  - The postantifungal effect (PAFE) of antimycotics on oral C. albicans isolates and
      its impact on candidal adhesion.
AB  - OBJECTIVE: Postantifungal effect (PAFE) is defined as the suppression of growth
      that persists following limited exposure of yeasts to antimycotics and subsequent
      removal of the drug. As there are no data on the PAFE of oral C. albicans
      isolates the main aim of this investigation was to measure the PAFE of 10 oral
      isolates of C. albicans following limited exposure (1 h) to five antifungal
      drugs, including nystatin which has not been previously used in PAFE assays. A
      secondary aim of the study was to evaluate the biological significance of PAFE,
      using a nystatin pre-exposed isolate of C. albicans and observing its adherence
      to denture acrylic surfaces, during the PAFE period. DESIGN: A total of 10 oral
      isolates of C. albicans were examined for the presence of the PAFE after 1 h
      exposure to five antifungal drugs, nystatin, amphotericin B, 5-fluorocytosine,
      ketoconazole and fluconazole. PAFE was automatically assessed with the help of a
      Spectramax machine which utilizes the principle of periodic turbidometric
      assessment of growth rates at a given temperature over a given period. The data
      thus collected are automatically processed in a graphic format as a computer
      printout. The PAFE was determined as the difference in time (h) required for
      growth of the drug-free control and the drug-exposed test cultures to increase to
      0.05 absorbance level following removal of the antifungal agent (by repeated
      washing). The adhesion of the single isolate to denture acrylic following limited
      exposure to nystatin was assessed by a previously described in vitro adhesion
      assay. RESULTS: Significant PAFE were observed for nystatin, amphotericin-B and 5
      fluorocytosine. A marginal PAFE was observed for ketoconazole and little or none
      for fluconazole. The mean duration of the PAFE of nystatin, amphotericin-B, 5
      fluorocytosine, ketoconazole and fluconazole were 2.89 (+/- 0.27) h, 2.83 (+/-
      0.23) h, 3.18 (+/- 0.31) h, 0.65 (+/- 0.11) h and 0.16 (+/- 0.06) h,
      respectively. The mean percentage reduction of adhesion of oral C. albicans
      BU47204 to denture acrylic during the PAFE period following exposure to nystatin
      for 10, 30, 50, 70 and 90 min was 9.12%, 61.73%, 65.99%, 82.16% and 83.14%,
      respectively. CONCLUSIONS: These in vitro findings imply that even a short period
      of exposure to antifungals may result in modulation of the growth and the
      virulent attributes of C. albicans, which however is largely dictated by the
      antimycotic agent in question. Whether such mechanisms operate in vivo needs to
      be clarified by further studies.

PMID- 10200706
TI  - Xylitol in caries prevention: what is the evidence for clinical efficacy?
AB  - Xylitol has attracted much attention as an alternative sweetener. Essentially all
      clinical studies concerning the effect of xylitol on caries development consent
      to its non-cariogenicity and to the beneficial effect of substituting sucrose
      with xylitol in chewing gums and sweets. However, claims of anti-caries or
      therapeutic effects, and superiority of xylitol over other polyols are still to
      be confirmed by well designed and conducted studies from independent research
      groups.

PMID- 10200707
TI  - Elimination of hypersensitive gagging reaction to dentistry by propofol at
      subhypnotic doses.
AB  - We describe a 44-year-old male patient with severe gagging reaction successfully
      treated without sedative effect by a continuous infusion of propofol. Propofol at
      subhypnotic doses seemed to be effective in eliminating hypersensitive gagging
      reaction to dentistry.

PMID- 10200708
TI  - Burkitt-like lymphoma presenting as a periodontal disease in AIDS patients: a
      report of two cases.
AB  - Burkitt-like lymphoma of the oral cavity is relatively uncommon in patients with
      acquired immunodeficiency syndrome (AIDS). The lesion usually appears as a
      solitary ulcerated mass with rapid onset. Some may present initially as gingival
      inflammation which delays final diagnosis and treatment. This report describes
      the presentations of multifocal intraoral Burkitt-like lymphoma in two Thai
      heterosexual men with AIDS. The clinical features and the radiographic findings
      in both cases mimicked a periodontal disease, showing extensive widening of the
      periodontal ligament space and loss of lamina dura in all segments of the molar
      teeth. The patients eventually died 5 and 14 months after they were diagnosed
      with HIV infection.

PMID- 10200709
TI  - Genetic disorders of the gingivae and periodontium.

PMID- 10200710
TI  - Drugs and oral disorders.
AB  - This chapter affirms that drugs and medicaments may have a profound effect on the
      periodontal structures. In some instances, such as drug-induced melanosis, the
      effect may be insignificant to the health of the patient. In other circumstances,
      drug-induced disorders may initiate painful, destructive disease processes that
      will not be successfully managed unless the causal role of drugs is recognized
      and altered. Finally, the clinician must remain aware of the contribution of drug
      induced xerostomia and smoking to increased susceptibility to dental and
      periodontal diseases.

PMID- 10200711
TI  - HIV infection and periodontal diseases.

PMID- 10200712
TI  - Infectious and tropical diseases affecting the human mouth.

PMID- 10200713
TI  - Mental disorders and periodontics.

PMID- 10200714
TI  - Mucocutaneous disorders.

PMID- 10200715
TI  - Gastrointestinal and granulomatous diseases.

PMID- 10200716
TI  - Gingival and periodontal aspects of diseases of the blood and blood-forming
      organs and malignancy.

PMID- 10200717
TI  - Do you practice marginal dentistry?

PMID- 10200718
TI  - Preimpregnated, fiber-reinforced prostheses. Part I. Basic rationale and complete
      coverage and intracoronal fixed partial denture designs.
AB  - This is the first of two articles describing the development and use of a
      continuous fiber-reinforced composite as a framework for the fabrication of fixed
      partial dentures and splints. The chemical composition and physical structure of
      the fiber-reinforced composite, along with the progression and development of a
      variety of fiber-reinforced composite materials, are discussed. Criteria for case
      selection, tooth preparation, and the clinical and laboratory procedures required
      for partial- or complete-coverage fixed partial denture fabrication and delivery
      are described.

PMID- 10200719
TI  - Alternatives to silver amalgam and resin composite in pediatric dentistry.
AB  - Silver amalgam has become a less attractive dental restorative material for
      restoration of primary teeth. After many decades of scientific and nonscientific
      controversy, use of silver amalgam for primary teeth is waning, not because of
      its mercury content but because dentistry has come up with more suitable
      materials. This article reviews the development and use of glass-ionomer silver
      cermet cements, resin-modified glass-ionomer cements, and polyacid-modified resin
      composites (compomers) for restoration of primary teeth.

PMID- 10200720
TI  - Candida albicans levels in patients with Sjogren's syndrome before and after long
      term use of pilocarpine hydrochloride: a pilot study.
AB  - OBJECTIVE: The purpose of this study was to compare the quantities of oral
      Candida albicans in patients with primary and secondary Sjogren's syndrome before
      and after the use of orally administered pilocarpine hydrochloride for 1 year.
      METHOD AND MATERIALS: Twelve female subjects with primary (n = 4) and secondary
      (n = 8) Sjogren's syndrome (mean age +/- SEM = 56.7 +/- 5.7 years) were enrolled
      in the study, after meeting rigid enrollment criteria. Oropharyngeal collection
      of samples and culturing was performed on each subject. Cultures specific for
      Candida albicans were plated into a culture media tube using the Oricult kit and
      also by serial dilutions and plating by a streptomycin-vancomycin technique.
      Cultures were incubated for 48 hours at 37 degrees C. The subjects used 5 mg of
      pilocarpine hydrochloride, administered orally three times daily, for 1 year,
      after which both of the Candida cultures were repeated. None of the subjects used
      antifungal medications, none smoked, and all were dentate. RESULTS: There was a
      significant difference in the prevalence of Candida after the use of pilocarpine
      hydrochloride for both groups. At the start of the study, 75% of all subjects
      were positive for Candida. Following the use of pilocarpine, 25% had positive
      cultures. There was also a decrease in the prevalence of clinical manifestations
      of infection from 75% of subjects to 25%. There was a significant decrease in the
      numbers of Candida cultured following the use of pilocarpine. CONCLUSION: Long
      term administration of pilocarpine hydrochloride resulted in a significant
      reduction in Candida albicans colonization in patients with primary or secondary
      Sjogren's syndrome.

PMID- 10200722
TI  - Microleakage of resin composite restorations with glass-ceramic inserts.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effects of glass-ceramic
      inserts and different application techniques of resin composites on marginal
      leakage. METHOD AND MATERIALS: Three groups of 10 standardized, round, Class V
      cavities were prepared on the buccal surface of 30 extracted human molar teeth.
      Group 1 received resin composite restorations, placed in one increment (bulk).
      Group 2 received resin composite restorations that were placed in two increments,
      and group 3 received resin composite restorations with beta-quartz ceramic
      inserts. After the teeth were thermocycled and placed in 0.5% basic fuchsin for
      24 hours, they were sectioned and examined for microleakage. RESULTS: On the
      occlusal margins, there was no statistically significant difference between the
      restorations placed with the incremental technique and the restorations with beta
      quartz inserts. The restorations placed with the bulk technique had significantly
      more microleakage than did the others. On the gingival margins, the restorations
      with beta-quartz inserts exhibited significantly less microleakage than did the
      other groups. The restorations placed with the bulk technique showed
      significantly more dye penetration than did the others. CONCLUSION: The use of a
      glass-ceramic insert reduced the marginal leakage of Class V resin composite
      restorations.

PMID- 10200723
TI  - An innovative direct technique for resin composite veneers for teeth with color
      alterations.
AB  - An alternative technique for fabricating resin composite veneers for teeth with
      color alterations is presented. The technique is based on research carried out
      with a silica derivative (coesite). The veneer is applied directly to the mouth.
      The objective of the technique is to provide greater translucence to the teeth,
      resulting in a better imitation of the natural appearance.

PMID- 10200721
TI  - A brief history and current status of metal-and ceramic surface-conditioning
      concepts for resin bonding in dentistry.
AB  - The bond strength of resin to metal or ceramic surfaces has been increased with
      the introduction of various surface-conditioning techniques. The principles of
      currently used conditioning methods and clinical trials with these methods are
      summarized. The advances in surface-conditioning methods have increased bonding
      to a high level; however, interpretation of the literature review indicates that
      chemical bonding by means of recently introduced techniques provides better
      results than does mechanical bonding.

PMID- 10200724
TI  - A scanning electron microscopic study of the effect of Gluma CPS bonding system
      on dentinal smear layers produced by different bur types and rotational speeds
      and on the resin-dentin interface.
AB  - OBJECTIVE: The purpose of this study was to investigate the effect of
      conditioners on smear layers produced by different bur types and rotational
      speeds and to study the interaction of subsequently applied primer and sealer
      with these conditioned surfaces. METHOD AND MATERIALS: Smear layers were produced
      on human teeth immediately after extraction by burs rotating at approximately
      6,000 rpm without water spray and 400,000 rpm with water spray. Gluma CPS etchant
      was applied for 15, 30, and 60 seconds, and a 20% phosphoric acid liquid
      (control) was applied for 30 seconds to smear layers. The specimens were prepared
      by critical point drying for scanning electron microscopic imaging within 24
      hours. Additional specimens were prepared and treated with Gluma CPS primer and
      sealer, according to the manufacturer's instructions. RESULTS: There were only
      small variations in the smear layer thicknesses with different bur types or
      speeds of rotation. Gluma CPS conditioner, applied for the recommended times, did
      not completely remove the smear layer. An altered smear layer, composed of a
      reaction product, remained on the dentinal surface. A zone of demineralization
      did occur, however, beneath the partially removed smear layer in both the 15- and
      30-second specimens but was only partly filled by primer and sealer. Smear layers
      were completely removed by the 20% phosphoric acid liquid to expose a delicate
      collagen network. CONCLUSION: An understanding of the appropriate treatment for
      smear layers is crucial to the development of improved dentin bonding systems.

PMID- 10200725
TI  - Clinical versus statistical significance.

PMID- 10200726
TI  - The limits to prediction: the future ain't what it used to be!

PMID- 10200727
TI  - Images in neuroscience. Brain development. XII. Maturation in brain activation.

PMID- 10200728
TI  - Biology and the future of psychoanalysis: a new intellectual framework for
      psychiatry revisited.
AB  - The American Journal of Psychiatry has received a number of letters in response
      to my earlier "Framework" article (1). Some of these are reprinted elsewhere in
      this issue, and I have answered them briefly there. However, one issue raised by
      some letters deserves a more detailed answer, and that relates to whether biology
      is at all relevant to psychoanalysis. To my mind, this issue is so central to the
      future of psychoanalysis that it cannot be addressed with a brief comment. I
      therefore have written this article in an attempt to outline the importance of
      biology for the future of psychoanalysis.

PMID- 10200729
TI  - Relationship between childhood behavioral disturbance and later schizophrenia in
      the New York High-Risk Project.
AB  - OBJECTIVE: An association between childhood behavioral disturbance and adulthood
      schizophrenia has been seen previously in retrospective or follow-back studies
      and in prospective studies. The authors examined the relationship between
      childhood behavioral problems and adulthood schizophrenia-related psychoses.
      Because a high rate of childhood behavioral problems is known to be associated
      with adult substance abuse, these analyses controlled for substance abuse.
      METHOD: The subjects of this investigation (N = 185) were offspring of parents
      with schizophrenia or affective disorder and of normal parents from the New York
      High-Risk Project (sample A). Data on childhood behavioral problems were obtained
      in a parent interview at initial assessment in 1971-1972. Adulthood outcomes
      (schizophrenia-related psychoses, affective disorders, anxiety disorders,
      substance abuse) were based on lifetime axis I diagnoses according to the
      Research Diagnostic Criteria. RESULTS: Substance abuse had a significant
      interaction with the clinical outcome groups. In subjects without substance
      abuse, those with schizophrenia-related psychoses had exhibited significantly
      more behavioral problems as children than had adult offspring with affective or
      anxiety disorder or with substance abuse only or no disorder. CONCLUSIONS: These
      results support the view that schizophrenia-related psychoses can be followed
      back to early behavioral disturbances. The confounding effects of substance abuse
      should be statistically controlled in studies of longitudinal associations
      between childhood behavioral disturbance and axis I outcomes.

PMID- 10200730
TI  - Association between memory complaints and incident Alzheimer's disease in elderly
      people with normal baseline cognition.
AB  - OBJECTIVE: Results of previous studies suggest that memory complaints may predict
      cognitive decline and dementia among elderly people in whom cognitive impairment
      is already apparent. However, cognitive decline is often a gradual process, and
      elderly people may notice that their memory deteriorates before mental status
      tests are able to detect any change in cognitive functioning. Therefore, the
      authors hypothesized that memory complaints would predict incident Alzheimer's
      disease in elderly subjects with no signs of cognitive impairment. METHOD: In the
      community-based Amsterdam Study of the Elderly, a sample of 3,778 nondemented
      persons, 65 to 84 years old, was selected and divided into two cognitive
      categories: normal (Mini-Mental State scores of 26-30) and borderline and
      impaired (Mini-Mental State scores less than 26). At baseline, the presence or
      absence of memory complaints was assessed. At follow-up, incident cases of
      Alzheimer's disease were diagnosed in a two-step procedure. RESULTS: After an
      average of 3.2 years, 2,169 persons were reevaluated, of whom 77 had incident
      Alzheimer's disease. Multivariate logistic regression analyses showed that memory
      complaints were associated with incident Alzheimer's disease in subjects with
      normal baseline cognition but not in subjects with impaired baseline cognition.
      CONCLUSIONS: The findings of this study suggest that memory complaints are a
      relatively strong predictor of incident Alzheimer's disease in older persons in
      whom cognitive impairment is not yet apparent. Furthermore, they suggest that
      older persons may be aware of a decline in cognition at a time when mental status
      tests are still unable to detect a decline from premorbid functioning.

PMID- 10200731
TI  - Psychological and behavioral functioning in adolescent psychiatric inpatients who
      report histories of childhood abuse.
AB  - OBJECTIVE: The purpose of this study was to examine psychological and behavioral
      functioning in psychiatrically hospitalized adolescents who report histories of
      childhood abuse. METHOD: Three hundred twenty-two subjects completed an
      assessment battery of psychometrically well-established instruments. Childhood
      abuse was assessed by using the childhood abuse scale of the Millon Adolescent
      Clinical Inventory. Childhood abuse scores of 30 or less and 70 or greater were
      used to create two study groups--no abuse (N = 93) and high abuse (N = 70),
      respectively. The two study groups were compared demographically and on the
      battery of instruments. RESULTS: The two groups differed substantially on most
      measures of psychological disturbance examined by the assessment battery. When
      age and depression level were controlled, the high-abuse group was characterized
      by significantly higher levels of dependency, suicidality, violence, impulsivity,
      substance use problems, and borderline tendency. Correlational analyses with the
      entire study group (N = 322) revealed that higher levels of these psychological
      problems were positively associated with higher levels of childhood abuse.
      CONCLUSIONS: Psychiatrically hospitalized adolescents who report childhood abuse
      present with a constellation of symptoms that, after removing the effects of
      depression, are consistent with borderline personality in statu nascendi.

PMID- 10200732
TI  - Predictors of treatment response from a first episode of schizophrenia or
      schizoaffective disorder.
AB  - OBJECTIVE: This study examined the treatment response of patients with first
      episode schizophrenia and schizoaffective disorder and potential predictors of
      response. METHOD: First-episode patients were assessed on measures of
      psychopathology, cognition, social functioning, and biological parameters and
      treated according to a standardized algorithm. RESULTS: One hundred eighteen
      patients (52% male, mean age 25.2 years) entered the study. The cumulative
      percentage of patients responding by 1 year was 87%; the median time to response
      was 9 weeks. The following variables were significantly associated with less
      likelihood of response to treatment: male sex, obstetric complications, more
      severe hallucinations and delusions, poorer attention at baseline, and the
      development of parkinsonism during antipsychotic treatment. Variables not
      significantly related to treatment response were diagnosis (schizophrenia versus
      schizoaffective disorder), premorbid functioning, duration of psychotic symptoms
      prior to study entry, baseline disorganization, negative and depressive symptoms,
      baseline motor function, akathisia and dystonia during treatment, growth hormone
      and homovanillic acid measures, psychotic symptom activation to methylphenidate,
      and magnetic resonance measures. CONCLUSIONS: Patients with first-episode
      schizophrenia and schizoaffective disorder have high rates of response to
      antipsychotic treatment; there are specific clinical and pathobiologic predictors
      of response.

PMID- 10200733
TI  - Health care utilization by older patients with coexisting dementia and
      depression.
AB  - OBJECTIVE: Few studies have examined the course of coexisting dementia and
      depression. The purpose of this study was to compare elderly patients who had
      coexisting dementia and depression with elderly patients who had either disorder
      alone in terms of their utilization of inpatient and outpatient services. METHOD:
      The study group included 7,115 veterans aged 60 years or older who had been
      discharged from Department of Veterans Affairs inpatient units in 1992 with
      diagnoses of major depression, dementia, or both. Outcome measures were analyzed
      for a 2-year period following the index hospitalization for each diagnostic study
      group. RESULTS: Patients with coexisting dementia and depression had
      significantly more psychiatric inpatient days than the other two study groups and
      more medical inpatient days and nursing home readmissions than patients with
      depression alone. Patients with coexisting dementia and depression had
      significantly more total inpatient days than the other two groups. Notably,
      patients with coexisting dementia and depression did not utilize more outpatient
      resources than the other study groups; in fact, they had significantly fewer
      medical, psychiatric, and total visits than patients with depression alone.
      CONCLUSIONS: The findings suggest that patients with coexisting dementia and
      depression are high utilizers of inpatient services, with a course of illness
      that may resemble dementia in terms of nursing home and inpatient medical care
      utilization and depression in terms of inpatient psychiatric care utilization;
      however, these patients utilized significantly fewer outpatient resources than
      the group with depression alone. Aggressive outpatient treatment approaches might
      reduce utilization of inpatient care for patients with coexisting depression and
      dementia.

PMID- 10200734
TI  - Psychiatric disorder and the broad autism phenotype: evidence from a family study
      of multiple-incidence autism families.
AB  - OBJECTIVE: Several studies have shown familial aggregation of some axis I
      psychiatric disorders in families ascertained through a single autistic proband.
      In this study the authors examined the rate of axis I psychiatric disorders in
      nonautistic relatives from multiple-incidence autism families and the possible
      relationship of these disorders to the broad autism phenotype. METHOD: The rates
      of axis I psychiatric disorders, assessed by using semistructured and family
      history interviews, were compared in parents, grandparents, and aunts and uncles
      ascertained through 25 families of multiple-incidence autism probands and 30
      families of probands with Down's syndrome. The possible association between
      selected psychiatric disorders and the broad autism phenotype, assessed directly
      through semistructured interviews and observational rating measures, was also
      examined in the two groups of parents. RESULTS: The parents of the autistic
      probands had significantly higher rates of major depressive disorder and social
      phobia than the parents of the Down's syndrome probands. The high rate of
      depression in the parents of the autistic probands was consistent with the high
      rates of depression and anxiety detected in the grandparents and aunts and uncles
      in the autism families by family history. There was no evidence of an
      association, within individuals, between either depression or social phobia and
      the broad autism phenotype. CONCLUSIONS: Relatives of autistic individuals have
      high rates of major depression and social phobia that are not associated with the
      broad autism phenotype and cannot be explained by the increased stress associated
      with raising an autistic child. Alternative mechanisms and the scientific and
      clinical implications of these findings are discussed.

PMID- 10200735
TI  - MRI volumes of the hippocampus and amygdala in adults with Down's syndrome with
      and without dementia.
AB  - OBJECTIVE: This study sought to determine whether volumes of the hippocampus and
      amygdala are disproportionately smaller in subjects with Down's syndrome than in
      normal comparison subjects and whether volume reduction is greater in Down's
      syndrome subjects with dementia. METHOD: The subjects were 25 adults with Down's
      syndrome (eight with dementia) and 25 cognitively normal adults who were
      individually matched on age, sex, and race. Magnetic resonance imaging measures
      included volumes of the hippocampus, amygdala, and total brain. Nineteen of the
      Down's syndrome subjects had follow-up scans (interscan interval = 9-41 months).
      RESULTS: Nondemented Down's syndrome subjects had significantly smaller volumes
      of the hippocampus, but not the amygdala, than their comparison subjects, even
      when total brain volume was controlled for. Volumes of both the hippocampus and
      the amygdala were smaller in the demented Down's syndrome subjects than in their
      comparison subjects, even when total brain volume was controlled for. Age was not
      correlated with volume of the hippocampus or amygdala among the nondemented
      Down's syndrome subjects and the comparison subjects; age was correlated with
      volume of the amygdala, but not the hippocampus, among the Down's syndrome
      subjects with dementia. Changes in volume over time were not statistically
      significant for either the demented or the nondemented subjects. CONCLUSIONS:
      Hippocampal volume, while disproportionately small for brain size in individuals
      with Down's syndrome, remains fairly constant through the fifth decade of life in
      those without dementia. All subjects over age 50 who had Down's syndrome
      demonstrated volume reduction in the hippocampus as well as clinical signs of
      dementia. Dementia was also associated with volume reductions in the amygdala
      that exceeded reductions in total brain volume.

PMID- 10200736
TI  - Problems reported by parents of children in multiple cultures: the Child Behavior
      Checklist syndrome constructs.
AB  - OBJECTIVE: The purpose of this study was to compare syndromes of parent-reported
      problems for children in 12 cultures. METHOD: Child Behavior Checklists were
      analyzed for 13,697 children and adolescents, ages 6 through 17 years, from
      general population samples in Australia, Belgium, China, Germany, Greece, Israel,
      Jamaica, the Netherlands, Puerto Rico, Sweden, Thailand, and the United States.
      RESULTS: Comparisons of nine cultures for subjects ages 6 through 17 gave medium
      effect sizes for cross-cultural variations in withdrawn and social problems and
      small effect sizes for somatic complaints, anxious/depressed, thought problems,
      attention problems, delinquent behavior, and aggressive behavior. Scores of
      Puerto Rican subjects were the highest, whereas Swedish subjects had the lowest
      scores on almost all syndromes. With great cross-cultural consistency, girls
      obtained higher scores than boys on somatic complaints and anxious/depressed but
      lower scores on attention problems, delinquent behavior, and aggressive behavior.
      Although remarkably consistent across cultures, the developmental trends differed
      according to syndrome. Comparison of the 12 cultures across ages 6 through 11
      supported these results. CONCLUSIONS: Empirically based assessment in terms of
      Child Behavior Checklist syndromes permits comparisons of problems reported for
      children from diverse cultures.

PMID- 10200737
TI  - Regional cerebral blood flow during script-driven imagery in childhood sexual
      abuse-related PTSD: A PET investigation.
AB  - OBJECTIVE: The purpose of this study was to determine whether anterior limbic and
      paralimbic regions of the brain are differentially activated during the
      recollection and imagery of traumatic events in trauma-exposed individuals with
      and without posttraumatic stress disorder (PTSD). METHOD: Positron emission
      tomography (PET) was used to measure normalized regional cerebral blood flow
      (CBF) in 16 women with histories of childhood sexual abuse: eight with current
      PTSD and eight without current PTSD. In separate script-driven imagery
      conditions, participants recalled and imagined traumatic and neutral
      autobiographical events. Psychophysiologic responses and subjective ratings of
      emotional state were measured for each condition. RESULTS: In the traumatic
      condition versus the neutral control conditions, both groups exhibited regional
      CBF increases in orbitofrontal cortex and anterior temporal poles; however, these
      increases were greater in the PTSD group than in the comparison group. The
      comparison group exhibited regional CBF increases in insular cortex and anterior
      cingulate gyrus; increases in anterior cingulate gyrus were greater in the
      comparison group than in the PTSD group. Regional CBF decreases in bilateral
      anterior frontal regions were greater in the PTSD group than in the comparison
      group, and only the PTSD group exhibited regional CBF decreases in left inferior
      frontal gyrus. CONCLUSIONS: The recollection and imagery of traumatic events
      versus neutral events was accompanied by regional CBF increases in anterior
      paralimbic regions of the brain in trauma-exposed individuals with and without
      PTSD. However, the PTSD group had greater increases in orbitofrontal cortex and
      anterior temporal pole, whereas the comparison group had greater increases in
      anterior cingulate gyrus.

PMID- 10200738
TI  - Serial CSF corticotropin-releasing hormone levels and adrenocortical activity in
      combat veterans with posttraumatic stress disorder.
AB  - OBJECTIVE: The authors sought to carefully test, by using a technique of
      continuous CSF sampling, the hypothesis that basal elevations in CSF
      corticotropin-releasing hormone (CRH) concentrations exist in patients with
      posttraumatic stress disorder (PTSD). They also sought to assess the relationship
      among PTSD symptoms, adrenocortical activity, and CSF CRH levels. METHOD: CSF was
      withdrawn by means of a flexible, indwelling subarachnoid catheter over a 6-hour
      period, and hourly CSF concentrations of CRH were determined for 11 well
      characterized combat veterans with PTSD and 12 matched normal volunteers. Twenty
      four-hour urinary-free cortisol excretion was also determined. PTSD and
      depressive symptoms were correlated with the neuroendocrine data. RESULTS: Mean
      CSF CRH levels were significantly greater in PTSD patients than in normal
      subjects (55.2 [SD = 16.4] versus 42.3 pg/ml [SD = 15.6]). No correlation was
      found between CSF CRH concentrations and PTSD symptoms. While there was no
      significant difference between groups in 24-hour urinary-free cortisol excretion,
      the correlation between 24-hour urinary-free cortisol excretion and PTSD symptoms
      was negative and significant. CONCLUSIONS: By using a serial CSF sampling
      technique, the authors found high basal CSF CRH concentrations and normal 24-hour
      urinary-free cortisol excretion in combat veterans with PTSD, a combination that
      appears to be unique among psychiatric conditions studied to date.

PMID- 10200739
TI  - Acute and chronic posttraumatic stress disorder in motor vehicle accident
      victims.
AB  - OBJECTIVE: This study reports the rates of acute and chronic posttraumatic stress
      disorder (PTSD) in a suburban community study group of 122 victims of serious
      motor vehicle accidents and a comparison group of 42 (who had been involved in
      minor, non-motor-vehicle accidents) followed over 12 months. METHOD: Motor
      vehicle accident victims were systematically recruited and examined with
      comparison subjects at 1, 3, 6, 9, and 12 months after the accident. The authors
      used the Structured Clinical Interview for DSM-III-R to assess DSM-III-R axis I
      disorders including PTSD. RESULTS: One month after the accident, 34.4% of the
      motor vehicle accident victims met criteria for PTSD (versus 2.4% of the
      comparison subjects). Similarly, at 3 and 6 months, rates of PTSD were higher
      (25.2% and 18.2%) in the motor vehicle accident victims than in the comparison
      group. Female victims were 4.64 times more likely than male victims to have PTSD
      at 1 month. Victims with a history of PTSD were 8.02 times more likely at 1 month
      and 6.81 times more likely at 3 months to have PTSD than those without a history
      of PTSD. Having an axis II disorder increased the risk for PTSD at 6 months.
      After adjustment for a history of PTSD and potentially confounding variables,
      women were 4.39 times more likely than men to develop PTSD at 1 month but did not
      have a higher risk for chronic PTSD; at 6 months, those with an axis II disorder
      were at greater risk of PTSD. CONCLUSIONS: Rates of PTSD are high in victims of
      serious motor vehicle accidents and remain high 9 months later. Female victims
      have an increased risk of acute but not chronic PTSD. Individuals with a history
      of PTSD are at risk of acute and chronic PTSD. An axis II disorder increases the
      risk for chronic but not acute PTSD.

PMID- 10200740
TI  - Symptom correlates of prepulse inhibition deficits in male schizophrenic
      patients.
AB  - OBJECTIVE: Information processing, inhibitory, and gating deficits in human and
      animal model studies of schizophrenia are demonstrated by using prepulse
      inhibition of the startle reflex. Prepulse inhibition deficits in schizophrenic
      patients correlate with core cognitive symptoms, such as thought disorder and
      distractibility, but their relationship to positive and negative symptoms of
      schizophrenia is less clear. METHOD: Fifty-one male schizophrenic patients and 26
      male normal comparison subjects were tested for prepulse inhibition of the
      eyeblink component of the startle reflex measured by electromyogram recording.
      Startling stimuli (118 dB) were presented alone (pulse only) or were preceded 60
      msec by discrete prepulse stimuli of 2, 4, 8, or 16 dB above the background 70-dB
      noise level. In addition, patients were assessed for demographic variables,
      generalized symptoms (Brief Psychiatric Rating Scale), and positive and negative
      symptoms. RESULTS: Schizophrenic and comparison groups differed significantly in
      the amount of prepulse inhibition produced by the 16-dB prepulse, with
      schizophrenic patients showing the expected deficient prepulse inhibition.
      Latency of the eyeblink response was generally slower for the schizophrenic
      patients, but the prepulse-induced latency facilitation for schizophrenic
      patients and comparison subjects did not differ significantly. The pattern of
      prepulse inhibition deficits in schizophrenic patients remained, with age and
      education controlled, in an analysis of covariance and subgroup matching.
      Deficient prepulse inhibition correlated with both positive and negative symptoms
      of schizophrenia. CONCLUSIONS: Under these experimental conditions, schizophrenia
      linked deficits in prepulse inhibition detected with a relatively strong prepulse
      are correlated with both positive and negative symptoms of schizophrenia. The
      level of correlation, while significant in this cohort, is not as robust as that
      in previous reports linking prepulse inhibition deficits with other measures,
      such as thought disorder. Future work should probably focus on the relationship
      of prepulse inhibition deficits to measures such as thought disorder rather than
      positive and negative symptoms.

PMID- 10200741
TI  - Gender differences in temporal lobe structures of patients with schizophrenia: a
      volumetric MRI study.
AB  - OBJECTIVE: The temporal lobe and associated structures have been previously
      implicated in the neuroanatomy of schizophrenia. This study was designed to
      assess the potential influence of gender on the morphology of temporal lobe
      structures, including the superior temporal gyrus and the amygdala/hippocampal
      complex, in patients with schizophrenia and to examine whether schizophrenic
      patients differ morphologically in these structures from comparison subjects.
      METHOD: Magnetic resonance imaging was used to measure the volume of temporal
      lobe structures, including the superior temporal gyrus, the amygdala/hippocampal
      complex, and the temporal lobe (excluding the volumes of the superior temporal
      gyrus and amygdala/hippocampal complex), and two comparison areas--the prefrontal
      cortex and caudate--in 36 male and 23 female patients with schizophrenia and 19
      male and 18 female comparison subjects. RESULTS: There was a significant main
      effect of diagnosis in the superior temporal gyrus and the amygdala/hippocampal
      complex, with smaller volumes in patients than in comparison subjects. There was
      a significant gender-by-diagnosis-by-hemisphere interaction for temporal lobe
      volume. Temporal lobe volume on the left was significantly smaller in male
      patients than in male comparison subjects. Female patients and female comparison
      subjects demonstrated no significant difference in temporal lobe volume. There
      were no statistically significant gender interactions for the superior temporal
      gyrus, the amygdala/hippocampal complex, or the comparison regions. CONCLUSIONS:
      These findings suggest that there may be a unique interaction between gender and
      the pathophysiologic processes that lead to altered temporal lobe volume in
      patients with schizophrenia.

PMID- 10200742
TI  - Improvement of schizophrenic patients with primary negative symptoms treated with
      amisulpride. Amisulpride Study Group.
AB  - OBJECTIVE: The goal of this placebo-controlled study was to evaluate the efficacy
      and safety of low doses of amisulpride, an atypical antipsychotic of the
      benzamide class with high affinity for D2 and D3 dopamine receptors, in the
      treatment of schizophrenic patients with predominantly primary negative symptoms.
      METHOD: After completion of a 4-week washout period, schizophrenic patients with
      primary negative symptoms participated in a 12-week, multicenter double-blind
      trial of placebo (N = 83), amisulpride, 50 mg/day (N = 84), or amisulpride, 100
      mg/day (N = 75). They were evaluated with the Scale for the Assessment of
      Negative Symptoms, the Scale for the Assessment of Positive Symptoms, the Brief
      Psychiatric Rating Scale, and the Montgomery-Asberg Depression Rating Scale.
      RESULTS: Both amisulpride treatment groups showed significantly greater
      improvement in negative symptoms than the placebo group. Positive symptom scores
      were low at baseline and changed minimally during the study, suggesting that the
      improvement in negative symptoms was independent of improvement in positive
      symptoms. The safety of amisulpride was comparable to that of placebo, and
      extrapyramidal symptoms were infrequent. Comparable efficacy and safety results
      were observed with either dose of amisulpride. CONCLUSIONS: These findings
      confirm and extend those of earlier placebo-controlled studies of low-dose
      amisulpride in the treatment of patients with predominantly negative symptoms of
      schizophrenia.

PMID- 10200743
TI  - Minor physical anomalies, dermatoglyphic asymmetries, and cortisol levels in
      adolescents with schizotypal personality disorder.
AB  - OBJECTIVE: A relationship between schizotypal personality disorder and
      schizophrenia has been documented in behavioral genetic studies, and there are
      similarities in the cognitive deficits and brain abnormalities associated with
      these disorders. Adolescents with schizotypal personality disorder are of
      particular interest because the postpubertal period is a critical one for the
      development of a DSM axis I disorder. It is likely that some schizotypal
      adolescents will remain stable over time, some will improve, and a subgroup will
      develop schizophrenia. This study tested the hypotheses that, like schizophrenic
      patients, schizotypal adolescents manifest an elevated rate of minor physical and
      dermatoglyphic anomalies, both of which suggest prenatal neurodevelopmental
      abnormalities. Cortisol release is also of interest because of evidence that the
      hypothalamic-pituitary-adrenal axis may influence the behavioral expression of
      vulnerability to schizophrenia. METHOD: Minor physical anomalies, dermatoglyphic
      asymmetries, and salivary cortisol levels were measured in three groups of
      adolescents: 20 with schizotypal personality disorder, 20 with other personality
      disorders, and 26 with no disorder. Assessments began at noon, and four saliva
      samples were obtained at hourly intervals. RESULTS: The schizotypal personality
      disorder group showed more minor physical anomalies and dermatoglyphic
      asymmetries than the normal comparison group and higher cortisol levels than both
      of the other groups. Group differences in cortisol level were most pronounced at
      the beginning of the evaluation. Cortisol level and age were positively
      correlated. CONCLUSIONS: The findings support the assumption that schizotypal
      personality disorder is associated with perturbations in fetal neurodevelopment
      and, under some circumstances, a heightened cortisol response.

PMID- 10200744
TI  - Psychosis in late life: how does it fit into current diagnostic criteria?

PMID- 10200746
TI  - Sexual disturbances during clozapine and haloperidol treatment for schizophrenia.
AB  - OBJECTIVE: The aim of this study was to evaluate the frequency and course of
      sexual disturbances associated with clozapine and haloperidol and their potential
      influence on compliance with medication regimens in patients with schizophrenia.
      METHOD: The authors prospectively investigated 153 patients with schizophrenia
      who received clozapine (N = 100) or haloperidol (N = 53) in a drug monitoring
      program. RESULTS: The frequency of sexual disturbances was lower in female
      patients than in male patients. There was no statistically significant difference
      between the patients taking haloperidol and those taking clozapine in the
      frequency of these disturbances. Clozapine plasma levels had a significant effect
      on diminished sexual desire and functional disturbances in male patients.
      Functional disturbances and diminished sexual desire did not have any influence
      on compliance in patients taking either haloperidol or clozapine. CONCLUSIONS:
      There was no statistically significant difference between haloperidol and
      clozapine in regard to their propensity to induce sexual side effects.

PMID- 10200747
TI  - Increase in expression of adhesion molecule receptors on T helper cells during
      antipsychotic treatment and relationship to blood-brain barrier permeability in
      schizophrenia.
AB  - OBJECTIVE: The authors estimated the expression of adhesion molecule receptors
      (VLA-4 and LFA-1) on T helper (CD4+) and T suppressor/cytotoxic (CD8+)
      lymphocytes in schizophrenic patients before and during antipsychotic treatment
      and studied the relationship of these subpopulations to CSF measures and blood
      brain barrier permeability. METHOD: Blood was drawn from hospitalized patients
      with schizophrenia before (N = 45) and after (N = 22) neuroleptic treatment and
      from an age-matched comparison group (N = 41). Lumbar punctures were performed on
      32 of the schizophrenic patients. RESULTS: During antipsychotic treatment there
      were significant increases in the percentage of VLA-4+/CD4+ and VLA-4+/CD8+
      cells. VLA-4+/CD4+ and LFA-1+/CD4+ cells were both closely related to disturbance
      of the blood-brain barrier. Higher values for VLA-4+/CD4+ and LFA-1+/CD4+ cells
      were found in patients with a disturbed blood-brain barrier. CONCLUSIONS: The
      findings suggest that adhesion molecules are involved in immunoregulation between
      the central nervous system and the peripheral immune system in schizophrenia.

PMID- 10200748
TI  - Stability of the diagnosis of deficit syndrome in schizophrenia.
AB  - OBJECTIVE: Primary, enduring negative symptoms have been distinguished from
      negative symptoms more generally and are used to define the deficit syndrome of
      schizophrenia. Although the validity of the deficit syndrome has been
      demonstrated by using brain imaging, neuropsychological, illness outcome, and
      developmental history data, the stability of this diagnostic category has not
      been tested prospectively by using direct patient assessments. METHOD: Forty
      three outpatients with schizophrenia and schizoaffective disorder were
      categorized into deficit and nondeficit groups an average of 3.8 years after
      having been previously categorized. RESULTS: There was 83% agreement between
      initial and blind follow-up designations of deficit status and 88% agreement on
      the nondeficit categorization. CONCLUSIONS: These results provide evidence for
      the long-term stability of the deficit syndrome in patients with schizophrenia
      and the reliability of the deficit/nondeficit categorization when diagnosed by
      those with appropriate training. Furthermore, they validate the method of
      categorizing deficit patients by using cross-sectional and retrospective data.

PMID- 10200749
TI  - Impaired glucose tolerance and abnormal movements in patients with schizophrenia.
AB  - OBJECTIVE: Diabetes mellitus has been implicated as a risk factor for tardive
      dyskinesia. The authors examined the association between abnormal movements and
      impaired glucose metabolism, which often precedes the development of overt
      diabetes, in patients with schizophrenia. METHOD: Twenty-one patients with DSM-IV
      schizophrenia receiving neuroleptic medication were given oral glucose tolerance
      tests involving serial glucose and insulin levels. These values were analyzed in
      relationship to abnormal involuntary movement ratings. RESULTS: Patients with
      impaired glucose tolerance had higher mean abnormal movement scores than those
      without glucose intolerance, but this difference was not statistically
      significant. There was, however, an association between the magnitude of the
      fasting insulin level and abnormal movements after the authors controlled for
      fasting glucose level. Additionally, the fasting glucose level predicted abnormal
      movements after the authors controlled for age. CONCLUSIONS: Hyperinsulinemia and
      hyperglycemia associated with insulin resistance may potentially contribute to
      the pathogenesis of tardive dyskinesia. Findings from this small cross-sectional
      study suggest a possible relationship that requires clarification through larger,
      longitudinal studies.

PMID- 10200750
TI  - Can enhanced acute-phase treatment of depression improve long-term outcomes? A
      report of randomized trials in primary care.
AB  - OBJECTIVE: The authors' goal was to determine whether improved outcomes from
      enhanced acute-phase (3-month) treatment for depression in primary care
      persisted. METHOD: They conducted a 19-month follow-up assessment of 156 patients
      with major depression in the Collaborative Care intervention trials, which had
      found greater improvements in treatment adherence and depressive symptoms at 4
      and 7 months for patients given enhanced acute-phase treatment than for patients
      given routine treatment in a primary care setting. Sixty-three of the 116
      patients who completed the follow-up assessment had received enhanced treatment,
      and 53 had received routine treatment in primary care. The Inventory for
      Depressive Symptomatology and the Hopkins Symptom Checklist were used to measure
      depressive symptoms. Automated pharmacy data and self-reports were used to assess
      adherence to and adequacy of pharmacotherapy. RESULTS: At 19 months, the patients
      who had received enhanced acute-phase treatment did not differ from those who had
      received routine primary care treatment in clinical outcomes or quality of
      pharmacotherapy. CONCLUSIONS: Even though enhanced acute-phase treatment of
      depression in primary care resulted in better treatment adherence and better
      clinical outcomes at 4 and 7 months, these improvements failed to persist over
      the following year. Continued enhancement of depression treatment may be needed
      to ensure better long-term results.

PMID- 10200751
TI  - Double-blind treatment of major depression with dehydroepiandrosterone.
AB  - OBJECTIVE: This study was designed to assess possible antidepressant effects of
      dehydroepiandrosterone (DHEA), an abundant adrenocortical hormone in humans.
      METHOD: Twenty-two patients with major depression, either medication-free or on
      stabilized antidepressant regimens, received either DHEA (maximum dose = 90
      mg/day) or placebo for 6 weeks in a double-blind manner and were rated at
      baseline and at the end of the 6 weeks with the Hamilton Depression Rating Scale.
      Patients previously stabilized with antidepressants had the study medication
      added to that regimen; others received DHEA or placebo alone. RESULTS: DHEA was
      associated with a significantly greater decrease in Hamilton depression scale
      ratings than was placebo. Five of the 11 patients treated with DHEA, compared
      with none of the 11 given placebo, showed a 50% decrease or greater in depressive
      symptoms. CONCLUSIONS: These results suggest that DHEA treatment may have
      significant antidepressant effects in some patients with major depression.
      Further, larger-scale trials are warranted.

PMID- 10200752
TI  - Breast-feeding and alcoholism: the Trotter hypothesis.
AB  - OBJECTIVE: The authors' goal was to determine whether early termination of breast
      feeding contributes to later alcohol dependence, as proposed more than 200 years
      ago by the British physician Thomas Trotter. METHOD: In 1959-1961, a multiple
      specialty group of physicians studied 9, 182 consecutive deliveries in a Danish
      hospital, obtaining data about prepartum and postpartum variables. The present
      study concentrates on perinatal variables obtained from 200 of the original
      babies who participated in a 30-year high-risk follow-up study of the antecedents
      of alcoholism. RESULTS: Of the 27 men who were diagnosed as alcohol dependent at
      age 30, 13 (48%) came from the group weaned from the breast before the age of 3
      weeks; only 33 (19%) of the 173 non-alcohol-dependent subjects came from the
      early weaning group. When challenged by other perinatal variables in a multiple
      regression analysis, early weaning significantly contributed to the prediction of
      the severity of alcoholism at age 30. CONCLUSIONS: The data support the
      hypothesis that early weaning may be associated with a greater risk of alcohol
      dependence later in life.

PMID- 10200753
TI  - Isoniazid-induced pellagra and the N-acetyltransferase gene genotype.

PMID- 10200754
TI  - Rapid remission of OCD with tramadol hydrochloride.

PMID- 10200755
TI  - Use of high-dose olanzapine in refractory psychosis.

PMID- 10200756
TI  - Fluoxetine for clomipramine withdrawal symptoms.

PMID- 10200757
TI  - Chronic psychotic illness from methamphetamine.

PMID- 10200758
TI  - Kandel's challenge to psychoanalysts.

PMID- 10200759
TI  - Kandel's challenge to psychoanalysts.

PMID- 10200760
TI  - Kandel's challenge to psychoanalysts.

PMID- 10200761
TI  - Kandel's challenge to psychoanalysts.

PMID- 10200762
TI  - Kandel's challenge to psychoanalysts.

PMID- 10200763
TI  - Kandel's challenge to psychoanalysts.

PMID- 10200764
TI  - Kandel's challenge to psychoanalysts.

PMID- 10200765
TI  - Tranquilizing effects of smoking cessation.

PMID- 10200766
TI  - Near-drowning experiences and panic disorder.

PMID- 10200767
TI  - Alveolar ventilation during hyperventilation by panic disorder patients.

PMID- 10200768
TI  - Estrogen for elderly men with dementia.

PMID- 10200769
TI  - Mood improvement from transcranial magnetic stimulation.

PMID- 10200770
TI  - Mood improvement from transcranial magnetic stimulation.

PMID- 10200771
TI  - Colorectal cancer screening.

PMID- 10200773
TI  - Helping someone with cancer.

PMID- 10200772
TI  - Colorectal cancer screening. ACS guidelines.

PMID- 10200774
TI  - Cancer statistics, 1999: challenges in minority populations.

PMID- 10200775
TI  - Cancer statistics, 1999.
AB  - The Surveillance Research Program of the American Cancer Society's Department of
      Epidemiology and Surveillance Research reports its 33rd annual compilation of
      cancer frequency, incidence, mortality, and survival data for the United States.

PMID- 10200776
TI  - Global cancer statistics.
AB  - Statistics are given for global patterns of cancer incidence and mortality for
      males and females in 23 regions of the world.

PMID- 10200777
TI  - Have nurse managers' perceptions of their competence changed over time?

PMID- 10200778
TI  - Board of Nursing decision puts patients at risk.

PMID- 10200779
TI  - Information dissemination and marketing in California.

PMID- 10200780
TI  - Graduate nursing administration programs are alive and well.

PMID- 10200781
TI  - Role transition for patient care vice presidents: from a single entity to a
      system focus.
AB  - The authors describe the process used and outcomes achieved by five patient care
      vice presidents who became a cohesive working group after the system integration
      of their separate organizations. Overcoming the hurdles that face any emerging
      group, these nurse executives developed a common patient-centered care delivery
      system and common leadership structure. They committed to four major leadership
      roles with common obligations and expectations for patient care vice presidents
      and hospital presidents, and role changes in terms of time spent as coach,
      interventionist, and crisis manager.

PMID- 10200782
TI  - Decision-making activity and influence of nurse executives in top management
      teams.
AB  - This study assesses the impact on decision-making when introducing the nurse
      executive into the top management team (TMT) in Veterans Affairs Medical Centers.
      Results indicate that nurse executives formally elevated to the TMT were no more
      likely to perceive greater involvement in decision-making than non-TMT nurse
      executives or nurses informally appointed to the TMT. However, nurse executives
      in all categories perceived themselves as more involved in strategic decisions
      than other TMT members.

PMID- 10200784
TI  - Nurses' perceptions: when is it a medication error?
AB  - This study investigates nurses' perceptions of medication errors and appropriate
      reporting. Results of the study suggest that nurses may not report because of
      fear of reprisal. Further, there may be a need to allow for nursing judgment in
      some instances; at those time, the term "medication error" may not be the most
      appropriate. Implications for nursing administration include further exploration
      of nonpunitive processes in response to adverse drug events.

PMID- 10200783
TI  - A developmental evaluation process for nurses: enhancing professional excellence.
AB  - Healthcare organizations are challenged to provide an environment that enhances
      professional growth. Miami Valley Hospital responded by examining its evaluation
      system for clinical nurses and designing a developmental evaluation process. The
      result is an objective position description outlining global responsibilities of
      a nurse and a comprehensive, unit-specific assessment of performance. As nurses
      are guided and nurtured in their development, the opportunities for them to excel
      are unlimited.

PMID- 10200785
TI  - Demystifying the influence of hospital characteristics on inpatient mortality
      rates.
AB  - Death, although not the only measure of adverse outcome, has been studied more
      than any other single occurrence. The authors discuss the findings of these
      studies and propose a conceptual framework to explain the relation between
      several hospital characteristics (e.g., profit status, RN ratios) and inpatient
      mortality rates. These studies raise the issue of whether some hospital
      characteristics are distal contributors and others, such as RN ratios, are more
      proximal explanatory variables of the mortality rate. Implications for
      understanding the relation of nursing's role in the array of potential
      contributors are discussed.

PMID- 10200786
TI  - US and Canada draw different conclusions on rBST.

PMID- 10200787
TI  - Ionizing radiation rules proposed, labeling discussed.

PMID- 10200788
TI  - HACCP seen as gateway.

PMID- 10200789
TI  - Believes irradiation important for food safety.

PMID- 10200790
TI  - Vaccination issues of concern to practitioners.

PMID- 10200791
TI  - What is your diagnosis? Nephroblastoma in a cockatoo.

PMID- 10200792
TI  - What is your diagnosis? Mass in the left nasal passage with evidence of
      mineralization.

PMID- 10200793
TI  - Anesthesia case of the month. Cyanosis in a dog during anesthesia.

PMID- 10200794
TI  - The future for third-party payment in veterinary medicine.

PMID- 10200795
TI  - Livestock sales and the uniform commercial code--what warranties are there?

PMID- 10200796
TI  - Serum alpha 1-acid glycoprotein concentrations before and after relapse in dogs
      with lymphoma treated with doxorubicin.
AB  - OBJECTIVE: To determine whether serum alpha 1-acid glycoprotein (AGP)
      concentration was a useful marker of relapse in dogs with lymphoma that were in
      clinical remission following treatment with doxorubicin. DESIGN: Cohort study.
      ANIMALS: 12 dogs with lymphoma and 10 healthy dogs. PROCEDURE: Serum AGP
      concentration was measured in the healthy dogs and in the dogs with lymphoma
      before treatment, 3 weeks after the first dose of doxorubicin was administered,
      and every 3 weeks thereafter until relapse (i.e., recurrence of clinically
      detectable disease such as palpable enlargement of peripheral lymph nodes). Serum
      AGP concentrations were determined by use of a radial immunodiffusion kit.
      RESULTS: Mean serum AGP concentration in healthy dogs was significantly less than
      concentration in dogs with lymphoma prior to treatment. Mean serum AGP
      concentrations after the first and each subsequent dose of doxorubicin were not
      significantly different from concentration in healthy dogs. However, mean serum
      AGP concentrations 3 weeks prior to and at the time of relapse were significantly
      higher than concentration measured after the first dose of doxorubicin, and were
      not significantly different from concentration measured before treatment.
      CLINICAL IMPLICATIONS: Results suggest that measuring serum AGP concentration may
      be a useful method of predicting relapse before recurrence of clinically
      detectable disease in dogs with lymphoma undergoing treatment with doxorubicin.

PMID- 10200797
TI  - Bee sting envenomation resulting in secondary immune-mediated hemolytic anemia in
      two dogs.
AB  - Immune-mediated hemolytic anemia secondary to bee envenomation developed in 2
      dogs. Clinical signs included lethargy, hematuria, ataxia, and seizures; 1 dog
      died. Clinicopathologic data included nonregenerative anemia, spherocytosis,
      positive results for Coombs' test, and occult hematuria. Treatment included oral
      administration of corticosteroids at immunosuppressive dosages and supportive
      care. The surviving dog initially responded to corticosteroids, but hemolysis
      recurred as the dosage was tapered. Hemolysis resolved with prolonged
      administration of corticosteroids. Bee venom contains hyaluronidase, histamines,
      and hemolysins that cause toxic and hemolytic effects. Envenomation should be
      considered in any dog with hemolytic anemia in which other causes are ruled out
      and exposure to bees is known.

PMID- 10200798
TI  - Clinical hypothyroidism associated with trimethoprim-sulfadiazine administration
      in a dog.
AB  - Treatment of a 9-year-old spayed female mixed-breed dog with trimethoprim
      sulfadiazine for a prolonged period resulted in clinical signs of hypothyroidism,
      and results of thyroid gland function tests were indistinguishable from those
      associated with endogenous hypothyroidism. Drug-induced hypothyroidism was
      diagnosed on the basis of history, normal thyroid uptake of sodium pertechnetate,
      and complete recovery of thyroid gland function after administration of
      trimethoprim-sulfadiazine was discontinued.

PMID- 10200799
TI  - Evaluation of peritoneal fluid pH, glucose concentration, and lactate
      dehydrogenase activity for detection of septic peritonitis in horses.
AB  - OBJECTIVE: To determine whether peritoneal fluid pH, glucose concentration, and
      lactate dehydrogenase activity can be used to differentiate horses with septic
      peritonitis from those with nonseptic peritonitis. DESIGN: Prospective study.
      ANIMALS: 46 horses, including 10 healthy horses, 15 horses with septic
      peritonitis, and 21 horses with nonseptic peritonitis. PROCEDURE: Peritoneal
      fluid and blood samples were analyzed for pH, glucose concentration, and lactate
      dehydrogenase activity. Complete blood cell counts were performed, and peritoneal
      fluid samples were submitted for bacterial culture. RESULTS: Horses with septic
      peritonitis had significantly lower peritoneal fluid pH and glucose
      concentrations than horses with nonseptic peritonitis and healthy horses.
      Compared with other tests, serum-to-peritoneal fluid glucose concentration
      differences > 50 mg/dl had the highest diagnostic use for detection of septic
      peritonitis. Peritoneal fluid pH < 7.3, glucose concentration < 30 mg/dl, and
      fibrinogen concentration > 200 mg/dl were also highly indicative of septic
      peritonitis. CLINICAL IMPLICATIONS: Peritoneal fluid pH and glucose concentration
      can be used to assist in the identification of horses with septic peritonitis.
      These measurements can provide an early indication of sepsis, especially if
      cytologic evaluation of peritoneal fluid is unavailable or results are equivocal
      and peritoneal fluid bacterial culture results are pending.

PMID- 10200800
TI  - Neodymium:yttrium-aluminum-garnet laser-assisted excision of progressive ethmoid
      hematomas in horses: 20 cases (1986-1996).
AB  - OBJECTIVE: To describe a technique of contact neodymium:yttrium-aluminum-garnet
      (Nd:YAG) laser-assisted excision of progressive ethmoid hematoma (PEH) in horses,
      to determine the recurrence rate of clinical signs of PEH in horses with follow
      up time of a minimum of 12 months, and to compare this result with reported
      results achieved by using conventional techniques. DESIGN: Retrospective study.
      ANIMALS: 21 horses with 26 PEH. PROCEDURE: Medical records of all horses with PEH
      treated by Nd:YAG laser excision from December 1986 through August 1996 were
      analyzed. Twenty-one horses underwent unilateral (18 surgeries) or bilateral (14)
      frontonasal bone flap with excision of the mass, using an Nd:YAG laser. One horse
      with bilateral PEH underwent a unilateral bone flap twice, 1 year apart. RESULTS:
      1 horse died. Four of 20 horses with followup times of 12 months or longer had
      recurrence of PEH. The PEH recurrence rate was 20% (5/25 PEH). Three of 6 horses
      with bilateral lesions had recurrence of PEH. Recurrence rate for horses that had
      bilateral PEH (3/6 horses) was greater than for horses with unilateral PEH (1/14
      horses). CLINICAL IMPLICATIONS: Treatment of PEH by Nd:YAG laser excision through
      a frontonasal bone flap results in a recurrence rate comparable with that
      reported for conventional techniques. Horses with bilateral lesions are more
      likely to have a recurrence of PEH.

PMID- 10200801
TI  - Comparison of medical and surgical treatment for impaction of the small colon in
      horses: 84 cases (1986-1996).
AB  - OBJECTIVE: To characterize clinical findings and compare effects of treatment and
      outcome for horses treated medically or surgically for impaction of the small
      colon. DESIGN: Retrospective study. ANIMALS: 84 horses with impaction of the
      small colon. PROCEDURE: Medical records were reviewed for history, physical
      examination findings, laboratory values, treatment, response to treatment,
      complications, out-come, and necropsy findings. RESULTS: 47 horses were treated
      medically and 37 horses were treated surgically. Significant differences between
      groups were not identified for duration of clinical signs, physical examination
      findings, or laboratory values. Horses treated surgically were hospitalized
      longer than horses treated medically. Complications recorded during
      hospitalization included diarrhea, jugular thrombophlebitis, recurrent colic,
      fever, and laminitis. Salmonella organisms were isolated from 20 horses. Horses
      treated surgically were more likely to have signs of moderate abdominal pain,
      gross abdominal distention, and positive results for culture of Salmonella spp
      than horses treated medically. Follow-up information was available for 27 horses
      treated medically and 23 horses treated surgically. Twenty-four (72%) and 21
      (75%) of the horses, respectively, survived and were being used for their
      intended purpose at least 1 year after treatment. CLINICAL IMPLICATIONS: Colitis
      may be a predisposing factor for impaction of the small colon in horses.
      Prognosis for horses treated surgically or medically is fair.

PMID- 10200802
TI  - Specificity of assays used by regulatory agencies to detect antibiotic residues
      in tissues of culled dairy cows.
AB  - OBJECTIVE: To determine percentage of false-positive test results for assays used
      by regulatory agencies to detect antibiotic residues in tissues. DESIGN:
      Prospective study. ANIMALS: 426 dairy cows. PROCEDURE: Dairy cows scheduled for
      culling that were identified as being unlikely to have antibiotic residues in
      tissues on the basis of strict inclusion criteria were used. A sample of kidney
      obtained from each cow at slaughter was tested on-site, using the swab test on
      premises (STOP; 97 samples) or the fast antibiotic screening test (FAST; 329
      samples). Frozen samples (n = 1,278) of liver, muscle, and kidney were thawed and
      retested at a federal laboratory, using the same screening assays. Kidney and
      liver samples (n = 852) were also tested using the 7-plate bioassay confirmation
      test used for confirmation and identification of antibiotic residues. RESULTS:
      Results of screening assays performed onsite were negative. When frozen samples
      were retested, 20 (12 liver, 7 kidney, and 1 muscle) had positive FAST results,
      but none had positive STOP results. Of the samples tested with the 7-plate
      bioassay confirmation test, 4 liver samples had results indicating a tetracycline
      (n = 3) or an unidentified microbial inhibitor (1) as a residue. CLINICAL
      IMPLICATIONS: Results suggest it is unlikely that regulatory action will be taken
      against producers sending untreated cattle to market. However, because results of
      the FAST and 7-plate bioassay confirmation test were positive when applied to
      frozen tissue, use of assays based on microbial inhibition may not be valid for
      confirmation of residues.

PMID- 10200803
TI  - Prevalence of Tritrichomonas fetus in a bull population and effect on production
      in a large cow-calf enterprise.
AB  - OBJECTIVE: To determine prevalence of infection with tritrichomonas fetus in a
      bull population; assess influence of age, breed, and grouping; assess effects on
      measures of cow performance (pregnancy rate, weaning percentage, weaning weight);
      and estimate test sensitivity. DESIGN: Epidemiologic study. ANIMALS: 1,383 bulls
      and records for 28,471 cows bred by these bulls in the immediate past breeding
      season. PROCEDURE: Bulls in 11 cattle units on a large ranch were tested for T
      fetus colonization by vigorous preputial scraping and protozoologic culture until
      no newly infected bulls were identified. Bull infection prevalence within units
      was calculated and correlated to production measurements reported for each cattle
      unit. RESULTS: Mean prevalence of T fetus-infected bulls was 11.9% (range, 0 to
      35.9%). Significant difference was detected between mean age of infected bulls
      (5.5 years) and noninfected bulls (3.9 years). Difference in prevalence among
      breeds was found, although other factors may have influenced this finding. Cow
      performance measurements (weaning percentage, mean weaning weight, and adjusted
      mean weaning weight/exposed cow) for cows exposed by breeding to bull groups with
      the highest prevalence of infection (35.9%) were significantly different from
      mean values for the entire study population. Test sensitivity for this study
      (73%) was less than that reported in other studies. CLINICAL IMPLICATIONS: T
      fetus infection in a natural service beef herd has an adverse impact on several
      production measures: Severity of impact is related to prevalence of infection in
      the bull population, where prevalence is bull age and population dependent.

PMID- 10200804
TI  - Estimation of lifetime productivity of female swine.
AB  - OBJECTIVE: To develop estimates of lifetime productivity for breeding female
      swine calculated longitudinally during time in the breeding herd, and to compare
      estimates of lifetime productivity for female swine removed from the herd at
      different parities. DESIGN: Retrospective cohort study. ANIMALS: 9,416 breeding
      female swine from 29 herds. PROCEDURE: A frequency distribution for parity at the
      time of removal was generated. Estimates of lifetime productivity (lifetime
      nonproductive days [NPD], lifetime NPD as a proportion of herd life, total number
      of pigs born per litter weaned, number of pigs born alive per litter weaned,
      number of pigs weaned per litter weaned, number of NPD per year in the herd,
      number of litters weaned per year in the herd, and number of pigs weaned per year
      in the herd) were calculated for females with parity > or = 1 at the time of
      removal. RESULTS: For 58% of all females, parity at the time of removal was < or
      = 3. On average, 20.7% of herd life was spent in nonproductive activities, but
      the proportion of herd life that was nonproductive decreased significantly as
      parity at the time of removal increased. Number of NPD per year in the herd
      decreased and number of litters weaned per year in the herd and number of pigs
      weaned per year in the herd increased significantly as parity at the time of
      removal increased. CLINICAL IMPLICATIONS: Higher parity at the time of removal
      from the herd is associated with improved lifetime productivity for female swine.
      Parity at time of removal is commonly used as an approximation for lifetime
      productivity, but it does not take into account the impact of NPD, especially NPD
      during early reproductive cycles.

PMID- 10200805
TI  - Infection control in the respiratory laboratory: risk, costs, expediency.

PMID- 10200806
TI  - Antipseudomonal antibiotics and cystic fibrosis.

PMID- 10200807
TI  - A cost-analysis of two approaches to infection control in a lung function
      laboratory.
AB  - BACKGROUND: The Thoracic Society of Australia and New Zealand (TSANZ) guidelines
      for infection control in respiratory laboratories are based on a 'Universal
      Precautions' approach to patient care. This requires that one-way breathing
      valves, flow sensors, and other items, be cleaned and disinfected between patient
      use. However, this is impractical in a busy laboratory. The recent introduction
      of disposable barrier filters may provide a practical solution to this problem,
      although most consider this approach to be an expensive option. AIM: To compare
      the cost of implementing the TSANZ infection control guidelines with the cost of
      using disposable barrier filters. METHODS: Costs were based on the standard tests
      and equipment currently used in the lung function laboratory at The Alfred
      Hospital. We have assumed that a barrier filter offers the same degree of
      protection against cross-infection between patients as the TSANZ infection
      control guidelines. Time and motion studies were performed on the dismantling,
      cleaning, disinfecting, reassembling and re-calibrating of equipment.
      Conservative estimates were made as to the frequency of replacing
      pneumotachographs and rubber mouthpieces based on previous equipment turnover.
      Labour costs for a scientist to reprocess the equipment was based on $20.86/hour.
      The cost of employing a casual cleaner at an hourly rate of $14.07 to assist in
      reprocessing equipment was also investigated. The new high efficiency HyperFilter
      disposable barrier filter, costing $2.95 was used in this cost-analysis. RESULTS:
      The cost of reprocessing equipment required for spirometry alone was $17.58 per
      test if a scientist reprocesses the equipment, and $15.56 per test if a casual
      cleaner is employed to assist the scientist in performing these duties. In
      contrast, using a disposable filter would cost only $2.95 per test. Using a
      filter was considerably less expensive than following the TSANZ guidelines for
      all tests and equipment used in this cost-analysis. CONCLUSIONS: The TSANZ
      infection control guidelines are expensive and impractical to implement. However,
      disposable barrier filters provide a practical and inexpensive method of
      infection control.

PMID- 10200808
TI  - Are antipseudomonal antibiotics really beneficial in acute respiratory
      exacerbations of cystic fibrosis?
AB  - BACKGROUND: Although anti-pseudomonal antibiotics are routinely used in the
      treatment of acute respiratory exacerbations of adult cystic fibrosis (CF), the
      specific efficacy of such treatment remains uncertain, the mechanism of action of
      these agents is not fully understood, and the role of sputum susceptibility
      testing in clinical decision making is controversial. AIMS: We investigated the
      relationship between susceptibility testing and clinical outcome in adult CF
      patients colonised with Pseudomonas aeruginosa. METHODS: Sputum samples were
      collected before, during and after respiratory exacerbations from 31 admissions
      (17 patients). Sputum colony counts and MIC of P. aeruginosa were performed.
      RESULTS: Sputum colony counts did not change significantly during or after
      intravenous (IV) antibiotic therapy. Clinical outcome parameters (lung function,
      12-minute walking distance, sputum weight and quality of life) were compared with
      susceptibility of P. aeruginosa colonies isolated at admission to the antibiotics
      used, and no correlation was evident. There was no evidence for the development
      of cross-resistance and there was no change in the proportion of mucoid colonies
      with therapy. CONCLUSIONS: While this study has a small patient sample size, it
      highlights the inconsistency of the role of antipseudomonal drugs also shown in
      other similar studies. The presence of P. aeruginosa in sputum of acutely ill CF
      patients prompts us to prescribe i.v. antipseudomonal drugs. If this approach was
      valid, we would expect to find a reduction in sputum colony counts and
      improvement in clinical parameters with the use of antibiotics to which the
      organisms were sensitive. The fact that such a relationship cannot be
      consistently demonstrated in this and other studies suggests that the use of
      antipseudomonal therapy in these patients requires more critical bacteriological
      and clinical evaluation.

PMID- 10200809
TI  - Walking with its training effects on the fitness and activity patterns of 79-91
      year old females.
AB  - BACKGROUND: Information is lacking about the physiological and psychosocial
      effects of exercise among very old persons. AIM: To investigate the effect of a
      twice-weekly, six-month progressive walking programme on 38 healthy women in
      their ninth decade, for evidence of the benefits of exercise. METHODS: Aerobic
      fitness, blood pressure, skinfold thickness and habitual activity patterns were
      studied in a randomised controlled trial. Women were chosen, as this is a group
      of increasing demographic importance for which studies are lacking. RESULTS: The
      training group and control group were not significantly different at baseline.
      However, after six months of progressive exercise the training group showed lower
      resting (p < 0.05) and working (p < 0.005) heart rates compared with non
      exercising controls. ANCOVA analyses indicated higher scores for the training
      group compared with the control group for Maximum Current Activity and Normative
      Impairment Index (both p < 0.001), which are both components of the Habitual
      Activity Profile. Morale also significantly improved within the training group (p
      < 0.01). CONCLUSIONS: These data show the trainability of very old women and the
      positive impact a low frequency, progressive exercise programme can have on
      cardiorespiratory fitness and daily living activity patterns. Such improvements
      are likely to be indicative of an enhanced outlook for independence.

PMID- 10200810
TI  - Efficacy, safety and tolerability of anagrelide in the treatment of essential
      thrombocythaemia.
AB  - BACKGROUND: Essential thrombocythaemia (ET) has an associated risk of thrombotic
      and haemorrhagic complications, which can be minimised by control of the platelet
      count. Anagrelide selectively lowers the platelet count, however, there is little
      Australasian experience with its use and scant data on symptom control. AIMS: To
      evaluate the efficacy of anagrelide for platelet reduction and symptom control in
      a broad cohort of patients with well-defined ET, and to determine the safety and
      tolerability in such a population. METHODS: Seventeen patients with ET and a
      platelet count > 600 x 10(9)/L were prospectively enrolled. The evaluable four
      males and 12 females with a median age of 58 years (range 14-79) included ten
      patients (63%) previously treated with two or more agents and 12 patients (75%)
      who had failed other therapies. The median follow-up was seven months (range 15
      days to 36 months). RESULTS: Anagrelide, in an average dose of 1.9 mg/day,
      reduced the platelet count from a mean of 728 x 10(9)/L (95% CI 611-845 x
      10(9)/L) to 412 x 10(9)/L (95% CI 319-504 x 10(9)/L) (p < 0.001) and maintained
      it at this level. Fourteen patients (88%) had a platelet reduction to < 600 x
      10(9)/L. All symptomatic patients had improvement in symptoms attributable to
      thrombocythaemia. There were three haemorrhagic and three thrombotic episodes in
      a total of three patients (19%), including one death from an intracerebral
      haemorrhage. Six patients (37%) were removed from therapy due to toxicity after a
      median of 151 days. Side effects included palpitations, abdominal pain and cough.
      CONCLUSIONS: Anagrelide is efficacious and safe in ET, both for platelet and
      symptom control. Minor side effects are common, however, tend to occur early and
      resolve spontaneously in most cases.

PMID- 10200811
TI  - Familial risk estimation in systemic sclerosis.
AB  - BACKGROUND: Familial systemic sclerosis has been rarely reported. Assumptions
      have therefore been made implying no familial disease aggregation. This study
      critically challenges the assumption using a methodical population-based
      epidemiological approach to quantify the prevalence and characteristics of
      familial systemic sclerosis. METHODS: In this retrospective cohort study the
      systemic sclerosis prevalence in first degree family members was compared between
      715 systemic sclerosis patients (710 families) and 371 randomly ascertained age
      and gender group-matched general practice controls (371 families). These data,
      obtained by telephone questionnaire (living patients) or medical records review
      (deceased patients and untraceable patients of unknown living status), were
      validated, where necessary, and expressed in terms of relative risk, absolute
      risk and population point prevalence. RESULTS: Systemic sclerosis affecting first
      degree members was validated in ten of 710 families. Reporting of systemic
      disease in another four more distant family members, and the co-occurrence of
      systemic and localised disease in three families was also documented. Observed
      and expected disease subtype concordance was 80% (44-97%) and 68% respectively
      and the female predominance among familial cases was similar to that for non
      familial disease. The risk of disease in a subsequent first degree relative was
      compared to the risk in an initial first degree family member. Its estimated
      magnitude was wide (11-158). However, use of population prevalence data to
      determine the expected number of systemic sclerosis patients in the negative
      cohorts' families suggests the higher estimate is more realistic. Despite the
      high magnitude, the absolute disease risk in first degree family members remained
      low--approximating 1%. The population prevalence of familial systemic sclerosis
      approximated 1.4/million. CONCLUSIONS: This study substantially increases the
      otherwise small list of documented instances of familial systemic sclerosis. More
      importantly, it quantifies the risk for the first time, ranking it as the
      disease's most powerful determinant identified to date.

PMID- 10200812
TI  - Systemic sclerosis prevalence and mortality in Sydney 1974-88.
AB  - BACKGROUND: Systemic sclerosis prevalence and mortality estimates have
      demonstrated wide variability. The sole Australian study published to date
      demonstrated high prevalence rates when compared to overseas estimates. The
      prevalence and mortality findings reported in this paper derive from a larger
      study which addressed the distribution and determinants of systemic sclerosis
      within Sydney. AIMS: To determine systemic sclerosis prevalence and mortality
      rates within Sydney over 15 years, 1974-88. METHODS: Cases were ascertained from
      multiple sources including death certificates, hospitals, physicians, vascular
      surgeons' and dermatologists' private practices, a systemic sclerosis self-help
      group and private medical laboratories. RESULTS: Overall, 715 cases were
      identified. Females comprised 77% (95% CI: 74-80) of cases. Disease of the
      limited subtype accounted for 79% (95% CI: 76-82) of all systemic sclerosis,
      being relatively more frequent in living than deceased cases, and in females than
      males. Crude prevalence estimates appeared to rise between 1975 (4.52/100,000 95%
      CI:3.75-5.29/100,000) and 1988 (8.62/100,000 95% CI:7.64-9.60/100,000) as did
      estimates of diffuse disease. However, diffuse disease prevalence, when expressed
      as a proportion of total disease prevalence, showed no significant temporal
      change. Although crude mortality rates also showed apparent temporal increases
      (0.24/100,000 in 1975 to 0.80/100,000 in 1988) standardised mortality rates
      showed less convincing trends (0.41/100,000 in 1976 and 0.40/100,000 in 1988).
      Death certificate-derived mortality rates provided relatively large
      underestimates of total mortality. However, these underestimates were relatively
      constant over time. CONCLUSIONS: This study has demonstrated systemic sclerosis
      prevalence and mortality rates comparable to overseas estimates, consistently
      higher prevalence and mortality rates in females than males, proportionally
      higher rates of diffuse disease in males than females and in deceased cases than
      living cases, a diffuse: limited disease ratio apparently stable over time,
      apparently increasing temporal prevalence and mortality rates and, by
      implication, rising incidence rates. The observed temporal rise in diffuse
      disease prevalence and the absence of a convincing fall in diffuse disease
      mortality suggests a rising temporal incidence rate of diffuse disease.
      Standardised mortality rates demonstrated less consistent trends than did crude
      mortality rates and failed to demonstrate convincing declines in mortality
      subsequent to the introduction of ACE inhibitors for management of systemic
      sclerosis renal disease. Death certificate-derived systemic sclerosis mortality
      rates considerably and consistently underestimated systemic sclerosis-all cause
      mortality.

PMID- 10200813
TI  - Atrial fibrillation: prevalence and management in an acute general medical unit.
AB  - BACKGROUND: Atrial fibrillation (AF) is a common comorbid condition in patients
      admitted to hospital. In managing patients with AF, recent research has
      highlighted the importance of heart rate control, cardioversion, maintenance of
      sinus rhythm and anticoagulation for the prevention of thromboembolism. AIM: To
      determine the prevalence of AF in patients admitted acutely to the general
      medical service at Auckland Hospital and to assess the adequacy of heart rate
      control, the number cardioverted and the use of warfarin to prevent
      thromboembolism. METHODS: Prospective review of all acute admissions to the
      general medical service over a 12 week period. Information was collected from
      hospital notes on the patients' present and past medical conditions, admission
      and discharge cardiac medication and the use of investigations, particularly
      thyroid function tests and echocardiography. The heart rate on discharge, number
      cardioverted either during the admission or after discharge and the number given
      warfarin and aspirin were recorded. RESULTS: One hundred and forty-seven patients
      (aged 38-96, mean age 76 years and 52% male) were admitted in AF 165 times out of
      the 1637 admissions over the study period (a prevalence of 10.4%, 95% CI 8.6
      11.5%). The main causes of admission were heart failure (23%), pneumonia or
      sepsis (17%), cerebrovascular accident (CVA) or transient ischaemic attack (TIA)
      (14%) and ischaemic heart disease (11%). Past medical history included
      hypertension (46%), ischaemic heart disease (39%), congestive heart failure
      (58%), valvular heart disease (12%), chronic obstructive airways disease (24%),
      CVA, TIA or thromboembolic event (24%) and diabetes (17%). Thyroid function tests
      were performed in 50% of patients and echocardiograms in 38%. Heart rate control
      at discharge could not be assessed, as this was not recorded prior to any
      patient's discharge. Seventy-eight per cent of patients were discharged on
      digoxin but only 29% on drugs that control the heart rate with exercise. Five
      patients out of 11 considered for cardioversion had a successful cardioversion in
      hospital and two were later cardioverted as outpatients. Twenty-eight per cent
      were discharged on warfarin, 33% on aspirin and one patient on both. Fifty-two
      per cent were considered to have contraindications to warfarin therapy.
      Prescribing rates for warfarin did not vary according to the patients' clinical
      risk for thromboembolism. CONCLUSION: AF is a common comorbid condition in the
      acute general medical ward. Standard investigations were under-utilised.
      Attention needs to be paid to the recording and control of heart rate at rest and
      on exercise. Cardioversion is considered infrequently. This patient group had a
      high risk for thromboembolism and after excluding the large group in whom
      warfarin was contraindicated, warfarin was still under-utilised.

PMID- 10200814
TI  - Improvements in outcomes for chronic obstructive pulmonary disease (COPD)
      attributable to a hospital-based respiratory rehabilitation programme.
AB  - AIM: To determine whether the benefits of pulmonary rehabilitation, demonstrated
      in selected subjects in randomised controlled studies, can be achieved by a
      hospital-based respiratory rehabilitation programme conducted as part of routine
      clinical management. METHODS:  DESIGN: A prospective longitudinal study of
      patients with severe chronic obstructive pulmonary disease (COPD) enrolled in a
      hospital based, non-medically supervised, outpatient, respiratory rehabilitation
      programme was undertaken. The rehabilitation programme was of pragmatic design
      and content, supervised by respiratory physiotherapists and comprised seven two
      hour sessions over one month for groups of six to eight patients. It included
      education on disease management, practical instruction in coping skills, as well
      as a progressive aerobic exercise programme for specific muscle training related
      to functional activities. Subjects were assessed prior to the programme but after
      optimisation of pharmacologic therapy, at the completion of the programme and at
      three months and six months post-programme. Principal outcome parameters were
      exercise capacity (as assessed by a six minute walk distance [MWD] test), degree
      of perceived breathlessness and quality of life (QOL) (assessed by the Chronic
      Respiratory Disease Questionnaire [CRDQ]). RESULTS: Fifty-one subjects with
      severe COPD (Fev1 = 0.9 +/- 0.4 1) completed the programme. There was a
      significant improvement in exercise capacity (a six MWD test improved from 375 +/
      126 m at baseline to 440 +/- 109 m at three months, p < 0.005). There were
      significant improvements in QOL (in the total CRDQ score as well as in the
      domains of dyspnoea, fatigue and mastery). There was a reduction in the level of
      perceived dyspnoea (modified Borg Scale). Most improvements were maintained for
      three and six months following completion of the programme. Compared with the six
      months preceding the programme there was a reduction in hospital admissions and
      reduction in courses of oral steroids. CONCLUSIONS: An outpatient, hospital-based
      respiratory rehabilitation programme pragmatically adapted for clinical utility
      produces substantial and clinically significant improvements in exercise
      tolerance and QOL, similar in type and magnitude to those obtained in controlled
      clinical trials. There was an associated reduction in COPD-related morbidity.
      Such gains were mostly maintained for six months after completion of the
      programme. Thus respiratory rehabilitation must be regarded as an essential
      component of a comprehensive clinical programme for the management of COPD.

PMID- 10200815
TI  - Investigation of a cluster of Staphylococcus aureus invasive infection in the top
      end of the Northern Territory.
AB  - INTRODUCTION: Staphylococcus aureus invasive infection remains a serious
      condition associated with considerable morbidity and mortality. Following
      notification of five cases at Royal Darwin Hospital (RDH), we searched for
      related cases, determined their epidemiological characteristics and attempted to
      identify the source of this apparent cluster. METHODS: We reviewed RDH
      microbiology records between June 1996 and April 1997 for S. aureus isolates with
      similar antibiograms to notified cases. We used antibiotic resistance patterns,
      bacteriophage typing and two molecular typing techniques to subtype implicated
      isolates. Hospital records were reviewed for admission details and associated
      costs were estimated. RESULTS: Fifty-four cluster-related isolates occurred in 47
      separate presentations. The peak incidence was in the wet season. The most
      important risk factor for staphylococcal invasive infection was the presence of
      skin sores/scabies in 17/54 cases (31%), followed by intravascular line use in
      14/54 (26%), open trauma in 11/54 (20%), underlying end stage renal failure and
      alcoholism each in ten of 54 (18%). The mean admission length was 30 days and
      antibiotics were given for an average of 23 days. Death due to S. aureus
      infection occurred in eight of 47 (17%) presentations. S. aureus pneumonia was
      community acquired in 12/13 patients (92%) and six of 13 (46%) died. Ten of 13
      (80%) pneumonia patients had at least one other focus of S. aureus infection. The
      cost of antibiotics and hospital bed per presentation was approximately $16,000.
      Presentations with skin sores/scabies cost considerably more ($31,000). No common
      epidemiologic features were found for community or hospital acquired cases.
      CONCLUSION: Considerable mortality and cost was attributable to cases of S.
      aureus invasive infection during this cluster; particularly those with community
      acquired pneumonia or skin sores/scabies. Staphylococcal antibiotic cover should
      be considered early for unwell patients presenting to hospital with pneumonia and
      other signs of potential S. aureus infection. It is appropriate to target public
      health efforts to prevent skin sores and to provide adequate treatment when they
      occur.

PMID- 10200816
TI  - Cytokines, Jaks, Stats, health and disease.

PMID- 10200817
TI  - Tuberculosis in non-residents in Western Australia.

PMID- 10200818
TI  - Vasculitic neuropathy and myopathy occurring as a complication of mixed
      connective tissue disease.

PMID- 10200819
TI  - Intestinal infarction secondary to anti-thrombin III deficiency associated with
      cytomegalovirus infection.

PMID- 10200820
TI  - Uterine cancer presenting with generalised dysaesthesia--a possible new
      paraneoplastic syndrome?

PMID- 10200821
TI  - Bilateral knee osteonecrosis in a patient with thrombotic thrombocytopenic
      purpura.

PMID- 10200822
TI  - 'Vegebilia'--a late complication of endoscopic sphincterotomy.

PMID- 10200823
TI  - Safe completion of planned combination chemotherapy despite septicaemic
      presentation of melioidosis.

PMID- 10200824
TI  - 'Wake up and smell the roses'--a drug reaction to etidronate.

PMID- 10200825
TI  - Cushing's syndrome due to surreptitious inhalation of fluticasone propionate.

PMID- 10200826
TI  - Symptomatic hypocalcaemia following intravenous pamidronate in cancer patients.

PMID- 10200827
TI  - Adult-onset Still's disease: a concise review of clues to an important rare
      syndrome.

PMID- 10200828
TI  - Cardiomyopathy secondary to ventricular tachycardia--an unusual case of
      reversible heart failure.

PMID- 10200829
TI  - Hypercalcaemia caused by Pneumocystis carinii pneumonia while in leukaemic
      remission.

PMID- 10200830
TI  - Helicobacter pylori and peptic ulcer disease...

PMID- 10200831
TI  - Sunscreens: are Australians getting the good oil?

PMID- 10200832
TI  - Renal biopsy precipitating catastrophic antiphospholipid syndrome, complicated by
      protein S deficiency and acute adrenal failure.

PMID- 10200833
TI  - Writing for AJOT.

PMID- 10200835
TI  - Clinical interpretation of "discharge planning in mental health: the relevance of
      cognition to community living".

PMID- 10200834
TI  - Discharge planning in mental health: the relevance of cognition to community
      living.
AB  - OBJECTIVE: The purpose of this study was to investigate the relationship between
      cognitive disability and performance of daily living skills and stability of
      cognitive level after discharge in a sample of adult psychiatric inpatients (N =
      40). METHOD: The Allen Cognitive Level Test-90 (ACL-90) was administered at time
      of discharge (Time I) and at 21 days to 28 days after discharge (Time II). The
      self-report version of the revised Routine Task Inventory (RTI-2) was also
      administered at Time II. RESULTS: No significant correlation was found between
      the ACL-90 at Time I and the RTI-2 scores; however, significant correlations were
      found between the ACL-90 scores at both times and between the ACL-90 score at
      Time II and the RTI-2 scores. CONCLUSION: The findings suggest that cognitive
      level remains relatively stable over a 1-month period in the postacute stage of a
      psychiatric illness. Cognitive level and performance of daily living skills are
      related, but the relationship is sensitive to time. Implications for occupational
      therapy assessment include recognizing the temporal constraints of functional
      assessments and refining instruments to be more sensitive to performance of
      familiar tasks, taking into consideration client adaptation to exigencies.

PMID- 10200836
TI  - The effect of context on skill acquisition and transfer.
AB  - OBJECTIVE: A major concern of occupational therapy is the identification of
      context characteristics that optimize performance. The purpose of this study was
      to examine the effect of context on skill acquisition and transfer. METHOD: Forty
      college students without disabilities (12 men, 28 women) were randomly assigned
      to the task of learning to use chopsticks in either a natural or a simulated
      context. Each participant practiced 60 trials in an acquisition phase on 1 day
      and was tested on a transfer task 24 hr after the acquisition phase. Their
      performances in the acquisition and transfer phases were measured with the
      variables of success rate and reaching kinematics. RESULTS: The natural context
      elicited significantly larger improvement of success rate in the acquisition
      phase and a significantly higher success rate in the transfer phase than the
      simulated context. No major difference was found in kinematic variables between
      the two contexts. CONCLUSION: These results suggested the use of natural contexts
      to facilitate the outcome of motor skill learning.

PMID- 10200837
TI  - Behavioral and physiological effects of deep pressure on children with autism: a
      pilot study evaluating the efficacy of Grandin's Hug Machine.
AB  - OBJECTIVE: One symptom common to many persons with autism is a high arousal or
      anxiety level. This study investigated the effects of deep pressure on arousal
      and anxiety reduction in autism with Grandin's Hug Machine, a device that allows
      self-administration of lateral body pressure. METHOD: Twelve children with autism
      were randomly assigned to either an experimental group (receiving deep pressure)
      or a placebo group (not receiving deep pressure but in the disengaged Hug
      Machine). All children received two 20-min sessions a week over a 6-week period.
      Arousal was measured behaviorally with the Conners Parent Rating Scale and
      physiologically with galvanic skin response (GSR) readings. RESULTS: Behavioral
      results indicated a significant reduction in tension and a marginally significant
      reduction in anxiety for children who received the deep pressure compared with
      the children who did not. Additionally, children in the experimental group, whose
      GSR measures decreased, on average, after deep pressure, were somewhat more
      likely to have higher GSR arousal a priori. CONCLUSION: These preliminary
      findings support the hypothesis that deep pressure may have a calming effect for
      persons with autism, especially those with high levels of arousal or anxiety.

PMID- 10200838
TI  - The effect of keeping an end-product on intrinsic motivation.
AB  - OBJECTIVE: According to literature in occupational therapy and psychology,
      intrinsic motivation is thought to be enhanced if people can keep the end-product
      of an activity. The purpose of this study was to examine the effect of keeping an
      end-product on intrinsic motivation. METHOD: Fifty participants chose one of four
      activities (painting a ceramic vase, decorating cookies, stringing beads for a
      necklace, creating stationery) and performed two conditions (keep, no-keep) in
      counterbalanced order. Participants were timed in each condition and, after each
      condition, ranked their self-determination and competence, which are
      psychological needs underlying intrinsic motivation. Participants were
      interviewed at the end of the study to examine their experiences. RESULTS:
      Participants worked significantly longer on a chosen activity when the end
      product could be kept and rated themselves significantly more self-determined and
      competent after performing the keep condition. However, further analysis revealed
      that these results depended on the activity chosen. CONCLUSION: The findings
      support that keeping an end-product can enhance performance of an activity.
      However, because results were not consistent across all activity choices, further
      research is needed to characterize the meaningfulness of particular activities.

PMID- 10200840
TI  - Factors influencing compliance with home exercise programs among patients with
      upper-extremity impairment.
AB  - OBJECTIVE: Patient cooperation and satisfaction with home exercise programs are
      important for successful outcomes of intervention. This study investigated
      factors from three models to predict increased compliance and satisfaction with
      home exercise programs: the Model of Human Occupation (MOHO), including the
      volition subsystem (interests), habituation subsystem (roles), and performance
      subsystem (reported physical capacity); the Health Belief Model (HBM), including
      perceived barriers, benefits, self-efficacy, and severity; and the Health Locus
      of Control (HLOC). METHOD: Sixty-two outpatients at an orthopedic upper-extremity
      rehabilitation facility completed a battery of questionnaires and self-report
      instruments, including a health belief survey to assess HBM factors, the
      Multidimensional Health Locus of Control Scale, the Modified Activity Profile to
      assess the performance subsystem of the MOHO, a demographic questionnaire
      (including roles), a report of home exercise, and a satisfaction scale of their
      therapist's treatment. Compliance was determined by comparing participants'
      report of exercises performed to exercises specified on their medical chart.
      RESULTS: Stepwise regression identified two predictors of compliance: perceived
      self-efficacy and internal HLOC, R2 = .16. CONCLUSION: Results supported the role
      of the MOHO's volition subsystem, but roles and physical capacity--representing
      the habituation and performance subsystems of the MOHO--did not contribute
      significantly to the prediction of compliance.

PMID- 10200839
TI  - Outcomes of protocol-based and adaptation-based occupational therapy
      interventions for low-income elderly persons on a transitional unit.
AB  - OBJECTIVES: The study objectives were to describe (a) adaptation trajectories of
      elderly persons treated on a transitional unit for deconditioning and tracked
      after their return to the community, (b) an individualized adaptation-based
      intervention provided to selected elderly persons in addition to protocol-based
      treatment for deconditioning, (c) goals and outcomes of these two interventions,
      and (d) contrasting perceptions of outcomes by elderly persons, their family
      members, and their therapists. METHOD: A longitudinal qualitative design was used
      to track 8 participants from transitional unit to community. Data on the protocol
      based intervention were obtained from chart review and therapist interviews. Data
      on the adaptation-based intervention were obtained from the Client-Centered
      Evaluation and Community Adaptive Planning Assessment, which were used for goal
      setting and problem solving. In the community, contrasting perspectives on
      outcomes were obtained from the participants, their family members, and their
      therapists through semistructured interviews. RESULTS: Participants' adaptation
      trajectories revealed that half relocated to new living arrangements after
      discharge from the transitional unit. At the time of follow-up, 91% of the
      protocol-based goals and 100% of the adaptation-based goals had been met in some
      fashion, with modification in the goal or development of new solutions in some
      cases. Outcomes valued by the participants were returning to former occupations
      and relationships; family members valued getting quality care for the
      participant; and therapists valued improvement in strength, endurance, and
      increased independence in activities of daily living (ADL). CONCLUSION: Findings
      support use of an individualized consultative intervention that addresses
      occupational performance areas and performance contexts combined with a protocol
      based, hands-on intervention that addresses performance components and basic ADL
      for elderly persons with multiple chronic illnesses.

PMID- 10200841
TI  - How to detect effects: statistical power and evidence-based practice in
      occupational therapy research.
AB  - The findings from 30 research investigations examining the effectiveness of
      occupational therapy interventions were reviewed and analyzed. The statistical
      conclusion validity was determined by computing post hoc power coefficients for
      the statistical hypothesis tests included in the examined studies. Data analysis
      revealed the median power values to detect small, medium, and large effect sizes
      were .09, .33, and .66, respectively. These results suggest a high probability of
      Type II errors in the sample of occupational therapy intervention research
      examined. In practical terms, this means the intervention produced a potentially
      useful treatment effect, but the effect was not detected as significant. Examples
      are provided that illustrate how low statistical power contributes to increases
      in Type II errors and inhibits the development of consensus through replication
      in the research literature. The presence of low-power studies with high rates of
      false negative findings prevents the establishment of guidelines for evidence
      based practice and impedes the scientific progress of rehabilitation professions
      such as occupational therapy.

PMID- 10200842
TI  - A meta-analysis of research on sensory integration treatment.
AB  - OBJECTIVE: The purpose of this study was to find whether existing studies of
      treatment using sensory integration approaches support the efficacy of these
      approaches. METHOD: With meta-analysis, the results of sensory integration
      efficacy research studies published from 1972 to the present were synthesized and
      analyzed. Sixteen studies were used to compare sensory integration effect with no
      treatment (SI/NT), and 16 were used to compare sensory integration effect with
      alternative treatments (SI/ALT). Overall average effect sizes, comparisons of the
      effect sizes for different dependent variables, and secondary factors associated
      with effect size variation were examined. RESULTS: The weighted average effect
      size of SI/NT studies was .29. However, there was a significant difference
      between the average effect sizes of the earlier studies (.60) and the more recent
      studies (.03). Of the outcome measures, larger effect sizes were found in the
      psychoeducational category (.39) and motor category (.40). Of SI/ALT studies, the
      average effect size was .09, not significantly different from zero. CONCLUSION:
      Three central conclusions can be made. First, in the SI/NT comparison, a
      significant effect was replicated for sensory integration treatment effects in
      earlier studies, but more recent studies did not show overall positive effects.
      Second, larger effect sizes were found in psychoeducational and motor categories.
      Third, sensory integration treatment methods were found to be as effective as
      various alternative treatment methods.

PMID- 10200843
TI  - Student perspectives on problem-based learning in an occupational therapy
      curriculum: a multiyear qualitative evaluation.
AB  - OBJECTIVES: Problem-based learning (PBL) is increasingly being used within health
      care professional educational programs to develop critical thinking skills via a
      learner-centered approach. However, few studies have evaluated the effect of
      participation in a PBL-centered curriculum on occupational therapy knowledge and
      skill development over time from the perspective of the students involved. This
      study examined student evaluations of the first three class cohorts participating
      in a PBL-based curriculum. METHOD: A participatory action design study involving
      qualitative, student-led focus groups was conducted with 154 students across 2
      years of the education program. Fourteen focus groups were audiotaped, and those
      audiotapes were transcribed by an outside expert, followed by two levels of
      analysis by program faculty members and a member check by student participants.
      RESULTS: Themes that emerged from the data analysis related to (a) defining
      elements of PBL, (b) the role of students and faculty members, (c) learning
      strategies used by students in a PBL versus traditional education program, (d)
      the challenges of a PBL approach, and (e) PBL's relationship to clinical
      reasoning and occupational therapy practice. CONCLUSIONS: Students perceived that
      a PBL approach adopted consistently across the curriculum contributed to the
      development of information management, critical reasoning, communication, and
      team-building skills; however, identified challenges were time and role
      management, information access, instructor versus PBL expectations and practices,
      and coping with the ambiguity of knowledge and reasoning.

PMID- 10200844
TI  - Sensory integrative-based occupational therapy and functional outcomes in young
      children with pervasive developmental disorders: a single-subject study.
AB  - OBJECTIVE: This single-subject study explored the effects of sensory integrative
      based occupational therapy provided in an outpatient clinic on the functional
      behaviors of two young children with pervasive developmental disorder (PDD) at
      home. METHOD: The participants were two 3-year-old boys with PDD. Before the
      study, the participants had not received a consistent program of sensory
      integrative-based occupational therapy. Before the baseline phase, three target
      behaviors were identified for each child, using an adapted version of Cook's
      revised Functional Behavior Assessment for Children with Sensory Integrative
      Dysfunction. These target behaviors were operationalized and used as repeated
      measures taken in the home during both the 2-week baseline and treatment phases.
      The treatment phase was 11 weeks for Participant 1 and 7 weeks for Participant 2.
      RESULTS: Both participants displayed significant improvements in the areas of
      social interaction, approach to new activities, response to holding or hugging,
      and response to movement. Decreases were noted in the frequency and duration of
      disruptive behaviors (e.g., high activity levels, aggressive behaviors), with an
      increase in functional behaviors, such as spontaneous speech, purposeful play,
      and attention to activities and conversation. Concurrent interventions that were
      not part of this study (e.g., initiation of speech therapy, preschool, vitamins)
      may have confounded these results. CONCLUSIONS: These findings support the
      application of sensory integrative-based occupational therapy as a part of the
      services provided to some children with PDD. Further research is needed to
      replicate these findings and to isolate the effects of sensory integrative-based
      occupational therapy because both participants were receiving other interventions
      at the time of this study.

PMID- 10200845
TI  - A comparison of two computer input devices for uppercase letter matching.
AB  - OBJECTIVE: To determine whether the Touch Window or the mouse with an enlarged on
      screen arrow was more effective or efficient for an on-screen letter-matching
      task completed by a boy 9 years of age with spastic quadriplegic cerebral palsy
      and visual and cognitive deficits. METHOD: A single-subject research design of 5
      treatment phases, A1, B1, A2, B2, and A & B, was used. The total percentage of
      correct letter matches per treatment session, the total percentage correct per
      letter, and the amount of time needed to match 5 consecutive letters correctly
      were evaluated. RESULTS: The range and variability of letters correctly matched
      per session decreased and trends for correct letter matches accelerated when the
      participant used the mouse interface. Accuracy with matching 18 of 26 (69%)
      letters of the alphabet increased when selections were made with the mouse
      interface. The participant was faster when using the Touch Window to match 5
      consecutive letters correctly; however, regardless of the interface device used,
      letter matching remained slow and tedious. CONCLUSION: The mouse with an enlarged
      on-screen arrow and cursor was the more effective interface device with this
      child. Making a minor adjustment such as increasing the size of the on-screen
      arrow can make a common piece of equipment accessible to a person with
      disabilities.

PMID- 10200846
TI  - The relationship between playfulness and coping in preschool children: a pilot
      study.
AB  - OBJECTIVE: Effective play and coping skills may be important determinants of
      children's adaptive behavior. Play and coping have undergone extensive individual
      study; however, these two variables have not been explored in relationship to
      each other. METHOD: The play behaviors of 19 randomly selected preschool children
      were rated by researchers using The Test of Playfulness. The children's coping
      skills were rated by their teachers with the Coping Inventory. RESULTS: A
      positive, significant correlation was found between children's level of
      playfulness and their coping skills. Overall, girls were rated as more playful
      than boys and scored higher in coping skills. Younger children (36-47 months of
      age) were rated as better players and copers than older children (47-57 months of
      age). CONCLUSION: This pilot study supports occupational therapy intervention in
      children's play environments and playful interactions as a way of influencing
      their adaptability in all life skills.

PMID- 10200847
TI  - Self-reported cumulative trauma symptoms among hospital employees: analysis of an
      upper-extremity symptom survey.

PMID- 10200848
TI  - A child's occupational performance: considerations of sensory processing and
      family context.
AB  - Sensory processing problems can be serious enough to affect a child's performance
      in school and home environments but often go undetected or are misunderstood.
      Poor sensory processing can affect a child's ability to successfully perform
      daily activities because of its effect on cognitive, sensory, and motor
      development. The relationship of sensory processing to children's occupational
      performance in their daily lives is an important consideration.

PMID- 10200849
TI  - Occupation into practice: worth another look?

PMID- 10200850
TI  - Compliance with sulfonylureas in a health maintenance organization: a pharmacy
      record-based study.
AB  - OBJECTIVE: To determine which factors affect compliance with sulfonylureas in a
      population served by a health maintenance organization in Southern California.
      METHODS: Retrospective analysis of pharmacy records and healthcare utilization
      data for two years (April 1993-March 1995), and a survey mailed to patients.
      Patients treated with sulfonylureas were selected for analysis on the basis of
      their prescription profile. Compliance was measured from the pharmacy records as
      the proportion of days the patient was in possession of the prescribed
      medications. Patient compliance with sulfonylureas was modeled as a function of
      four clusters of determinants: patient-related attributes, drug regimen
      characteristics and complexity, health status and disease-related variables, and
      characteristics of the interaction with healthcare providers. RESULTS: 786
      patients were identified for analysis (49.1% women, mean age 59 y). The mean
      compliance rate was 83% +/- 22% SD. Compliance was significantly positively
      related with age and self-reported level of medication-taking compliance at
      baseline. Factors shown to have an inverse relationship with compliance were
      treatment complexity, perception of general health, and being a newly treated
      patient (adjusted R2 for the final model = 0.148). CONCLUSIONS: Our results
      suggest that factors found to be associated with noncompliant behavior (e.g.,
      being a newly treated patient, self-reported compliance, regimen complexity) can
      be assessed by physicians and pharmacists as a routine practice.

PMID- 10200851
TI  - Contemporary utilization of digoxin in patients with atrial fibrillation.
      Clinical Quality Improvement Network Investigators.
AB  - OBJECTIVE: To define the contemporary practice patterns of digoxin utilization
      for the management of patients with atrial fibrillation (AF). METHODS: A
      retrospective medical records audit of 2490 patients with documented AF, from 12
      Canadian hospitals and six outpatient clinics, during fiscal year 1993-1994, was
      conducted. RESULTS: There were 1158 women and 1332 men, with a mean age of 72
      years; 956 patients were < 70 years of age and 1534 were > or = 70 years old. The
      majority of patients had nonvalvular AF (75% of those with a documented
      etiology). Paroxysmal AF (PAF) was documented in 800 patients, 936 had chronic
      AF, and 754 had new-onset AF. While the prescribing patterns were heterogeneous,
      the predominant strategy pursued in all subgroups appeared to be that of
      achieving rate control. Digoxin was the most commonly prescribed medication (79%)
      and was prescribed for the majority of patients in all subgroups, including
      patients with PAF (74%) and patients with a history of chronic AF who were
      currently in sinus rhythm (83%). Only 10% of the patients with PAF who were
      prescribed digoxin had congestive heart failure. Similarly, less than 25% of the
      patients with chronic AF who were prescribed digoxin after conversion to sinus
      rhythm had evidence of heart failure. CONCLUSIONS: In the absence of clinical
      trial evidence supporting either a strategy of antiarrhythmic therapy or rate
      control with anticoagulation, the appropriateness of the observed prescribing
      practices cannot be judged. However, digoxin is not the best rate-controlling
      agent for all patients and may be overused in certain subgroups of patients, such
      as those with PAF and those successfully converted to sinus rhythm.

PMID- 10200852
TI  - Nonprescription and alternative medication use by individuals with HIV disease.
AB  - OBJECTIVE: To examine the strength of the associations between predisposing,
      enabling, and need-for-care variables and the self-treatment of HIV disease; and
      to compare sociodemographic and illness-related factors associated with the use
      of vitamins, nonprescription medications, herbs, and recreational substances
      among HIV-infected individuals. METHODS: Data were derived from 7887 interviews
      conducted as part of the AIDS Cost and Services Utilization Survey. The
      conceptual framework was the Andersen Behavioral Model of Health Services Use.
      Factors associated with nonprescription and alternative medication use were
      assessed using logistic regression. Generalized estimating equations were applied
      to adjust variance estimates for within-person correlations of drug use over
      time. RESULTS: After adjusting for perceived health status, T cell count, and
      stage of disease, the results indicated that African-Americans were less likely
      to use nonprescription drugs (odds ratio [OR] 0.65, 95% CI 0.52 to 0.81),
      vitamins (OR 0.59, 95% CI 0.48 to 0.73), and herbs (OR 0.41, 95% CI 0.22 to
      0.76), compared with non-Hispanic whites. Similarly, Hispanics were less likely
      to report use of herbs (OR 0.58, 95% CI 0.34 to 0.98) or recreational drugs (OR
      0.34, 95% CI 0.15 to 0.76) than were non-Hispanic whites. Oppositely, individuals
      who had a college education were more likely to use vitamins (OR 1.26, 95% CI
      1.05 to 1.50) and herbs (OR 2.47, 95% CI 1.56 to 3.91). Enabling variables such
      as insurance status and income were generally associated only with use of
      recreational drugs. Need-for-care variables were generally associated only with
      use of nonprescription drugs and vitamins. CONCLUSIONS: Predisposing, enabling,
      and need-for-care variables from the Andersen Behavioral Model were significantly
      associated with the use of four categories of drugs to self-treat HIV disease.
      However, there was not a consistent pattern across the drug categories.

PMID- 10200853
TI  - INR elevation associated with diarrhea in a patient receiving warfarin.
AB  - OBJECTIVE: To report a case of international normalized ratio (INR) prolongation
      in a patient receiving warfarin who experienced several episodes of diarrhea.
      CASE SUMMARY: A 56-year-old white woman, previously controlled on warfarin
      therapy (INR 2.5-3.5) after aortic valve replacement, experienced six episodes of
      INR elevation, each associated with an acute bout of diarrhea lasting from one to
      four days. The patient had not received additional warfarin or new medications
      (including nonprescription medications and herbal remedies) prior to the
      episodes. The patient had no obvious signs of bleeding (except bruising on 1
      episode) or signs of infection determined through physician evaluation of the
      patient and her stools. In addition, she had no diagnosis of liver disease or
      acute or chronic malabsorption. The patient did report that her dietary intake
      decreased to 25-50% of normal during these episodes of diarrhea, which may result
      in decreased vitamin K ingestion. DISCUSSION: This is one of the first case
      reports documenting a trend of INR elevation specifically with episodes of
      diarrhea. Since most of the common reasons for acute INR elevation have been
      eliminated, diarrhea with decreased oral intake are the most probable causes for
      these observed changes in the INR. Several reports suggest that acute diarrhea
      results in malabsorption of vitamin K, which can predispose patients taking
      warfarin to INR elevations, but in many of these reports patients had other risk
      factors for INR elevation. Although the effect of diarrhea on vitamin K
      absorption and the INR is difficult to quantify, the INR elevation reported here
      seemed to be directly associated with the duration of each diarrheal episode.
      CONCLUSIONS: Diarrhea episodes in patients receiving warfarin can result in
      prolongation of the INR and possible bleeding. Patients who experience diarrhea
      or decreased oral intake resulting in elevated INRs should have their INRs
      evaluated more frequently and their warfarin doses adjusted appropriately.

PMID- 10200854
TI  - Bupropion mimics a transient ischemic attack.
AB  - OBJECTIVE: To report the development of symptoms suggesting transient ischemic
      attacks during bupropion treatment for smoking cessation. CASE SUMMARY: A 67-year
      old white man experienced paresthesia, dizziness, tinnitus, confusion, and gait
      impairment shortly after starting bupropion as an aid to smoking cessation.
      Bupropion was discontinued on hospital admission, and testing for vertebral
      basilar artery disease was negative. His symptoms resolved, and he remained
      asymptomatic until restarting bupropion two days after hospital discharge.
      DISCUSSION: Although separate case reports have reported sensory disturbances,
      tinnitus, and balance impairement associated with bupropion use, the combination
      of symptoms occurring in this patient has not been previously published.
      CONCLUSIONS: The temporal relationship between bupropion exposure and
      symptomatology suggests that bupropion caused symptoms mimicking transient
      ischemic attacks in this patient.

PMID- 10200855
TI  - High anion gap metabolic acidosis associated with aminocaproic acid.
AB  - OBJECTIVE: To report a case of high anion gap metabolic acidosis related to
      infusion of aminocaproic acid (ACA) that temporarily corrected during
      hemodialysis and resolved upon ACA discontinuation. CASE SUMMARY: A 65-year-old
      white woman with staphylococcal sepsis complicated by acute renal failure was
      treated with ACA to control a hemorrhagic coagulopathy. After receiving an
      initial 5-g bolus of ACA, she received a continuous intravenous infusion of 500
      mg/h for just over 5 days, then 250 mg/h for a final 12 hours. Immediately after
      beginning ACA therapy, she developed a severe anion gap metabolic acidosis that
      briefly improved after hemodialysis. The condition resolved completely only after
      the discontinuation of ACA and therapy with a systemic alkalinizer. DISCUSSION:
      ACA is not among the previously identified causes of high anion gap metabolic
      acidosis. The temporal profile relating anion gap to ACA initiation, hemodialysis
      treatment, and ACA discontinuation supports causality in this case. The magnitude
      of increase in the anion gap appears to have been proportional to the dose of
      ACA. CONCLUSIONS: In patients with renal impairment, ACA administration may
      produce a dose-related, high anion gap metabolic acidosis that might be
      reversible during hemodialysis. Insufficient data are available, but when ACA
      must be used in such patients, a more conservative dosing of ACA should be
      coupled with close monitoring.

PMID- 10200856
TI  - Rhabdomyolysis associated with naltrexone.
AB  - OBJECTIVE: To report a possible association between naltrexone therapy and the
      development of rhabdomyolysis in one patient. CASE SUMMARY: A 28-year-old white
      man in good physical health was started on naltrexone 50 mg/d for inpatient
      treatment of alcohol dependence and depression. A routine serum chemistry panel
      obtained on day 9 of naltrexone therapy showed marked new elevations in creatine
      kinase and aspartate aminotransferase. The patient remained asymptomatic and did
      not develop renal insufficiency. The serum enzyme concentrations returned to
      normal within eight days of naltrexone discontinuation. DISCUSSION:
      Rhabdomyolysis has not been previously reported to occur in patients during
      treatment with naltrexone. Alcoholism may result in a reversible acute muscle
      syndrome, but our patient did not fit the appropriate clinical profile for such a
      syndrome. Additionally, the other prescribed medications could not be implicated
      as possible causative agents. CONCLUSIONS: This case report illustrates a
      possible association between naltrexone therapy and rhabdomyolysis.

PMID- 10200857
TI  - Contamination of antibiotics resulting in severe pediatric methadone poisoning.
AB  - OBJECTIVE: To report an accidental contamination of antibiotic suspension by
      methadone that occurred in a retail Canadian pharmacy, leading to severe
      poisoning in a young child. CASE SUMMARY: A 4 1/2-year-old healthy Asian boy was
      prescribed amoxicillin suspension for cough and fever. Shortly after receiving
      the second dose of 5 mL he became drowsy and less responsive. On admission, he
      was arousable by deep pain, and pinpoint pupils were noted. A urine sample sent
      for a toxicology screen revealed the presence of methadone and its metabolite.
      Blood methadone concentrations were 0.23 and 0.14 mg/L, five and nine hours after
      the second dose of amoxicillin was given, respectively. The amoxicillin
      suspension was tested for methadone and was found to have a concentration of 2.4
      g/L. The child gradually improved and was discharged on day 4 in good condition.
      The pharmacy in which the antibiotic was dispensed has been a dispensing center
      for a local methadone maintenance program, and methadone was accidentally mixed
      with the antibiotics. DISCUSSION: In this case, a near fatal outcome occurred
      when methadone was inadvertently mixed with antibiotics in a community pharmacy.
      A literature search revealed two previous reports of opiate toxicity in children
      following ingestion of oral antibiotic preparations. CONCLUSIONS: Prompt action
      is needed in Canadian pharmacies that dispense methadone in order to minimize
      such errors in the future. General practitioners, pediatricians, and emergency
      department physicians should recognize and suspect this rare cause of opiate
      toxicity in a child. In a patient presenting with a decreased level of
      consciousness and miosis, with or without respiratory depression, naloxone
      administration should be considered, whether or not a history of opioid ingestion
      is obtained.

PMID- 10200858
TI  - Reteplase: a new thrombolytic for the treatment of acute myocardial infarction.
AB  - OBJECTIVE: To summarize the published data on reteplase, the most recent
      thrombolytic agent approved by the Food and Drug Administration for use in the
      management of acute myocardial infarction in adults. DATA SOURCES: Published data
      on reteplase identified by MEDLINE searches (January 1985-June 1997), as well as
      other pertinent literature. DATA SYNTHESIS: Reteplase is a new thrombolytic agent
      derived from human tissue plasminogen activator. Its mechanism of action is
      similar to that of alteplase, but it differs in pharmacokinetic and
      pharmacodynamic properties. Certain structural changes contribute to differences
      in pharmacokinetic properties such as a prolonged half-life (15 min), which
      allows it to be administered as two 10-MU bolus injections. Reteplase has been
      shown to have fibrin specificity similar to that of alteplase, but with a lower
      binding affinity for fibrin. This enables reteplase to bind to the thrombus
      repeatedly and increases its fibrinolytic potential. In clinical trials,
      reteplase demonstrated more rapid and complete coronary patency compared with
      alteplase, without a significant increase in clinical adverse events. However,
      the improvement in coronary artery patency with reteplase versus alteplase did
      not result in a reduction in mortality in the GUSTO III trial. CONCLUSIONS:
      Despite evidence that use of reteplase results in an improved coronary artery
      patency rate versus accelerated infusion alteplase, an improvement in mortality
      rate with reteplase was not shown. Reteplase may have an advantage over alteplase
      due to a more rapid and simpler dosing regimen, but the significance of this
      difference is yet to be determined.

PMID- 10200860
TI  - Epoprostenol in primary pulmonary hypertension.
AB  - OBJECTIVE: To review briefly the epidemiology, pathophysiology, and current
      treatment of primary pulmonary hypertension (PPH) and review the available
      clinical data on epoprostenol in PPH. DATA SOURCES: A MEDLINE search (January
      1966-August 1998) was used to identify case reports and clinical studies
      pertaining to epoprostenol in PPH. Bibliographic lists were also used. STUDY
      SELECTION: All English-language clinical studies of epoprostenol in PPH were
      included. Incomplete study descriptions (abstracts) were not included. DATA
      EXTRACTION: Study design, population, methods, clinical outcomes, and adverse
      effects were evaluated. DATA SYNTHESIS: PPH is a relatively rare disease that
      results in symptoms of congestive heart failure and has a five-year survival rate
      of 34%. Therapy has consisted of vasodilators, anticoagulation, oxygen, and
      ultimately lung transplantation. Epoprostenol, which has recently become
      available as an integral pharmacotherapeutic option, has been shown to improve
      hemodynamic parameters such as cardiac output, pulmonary artery pressure, and
      pulmonary vascular resistance. It has been shown to improve exercise parameters,
      New York Heart Association (NYHA) functional class, and survival. Epoprostenol is
      indicated for patients with severe disease (NYHA class III or IV) who do not
      respond to acute vasodilator challenge or chronic calcium-channel blocker
      therapy. Its chronic administration is challenging as it requires continuous
      infusion via central venous catheter and a special infusion pump. Administration
      is further complicated by the 48-hour expiration of reconstituted epoprostenol
      and the need to refrigerate the reconstituted drug. CONCLUSIONS: Epoprostenol
      improves hemodynamics and clinical outcome in patients with severe PPH.
      Epoprostenol therapy requires intensive patient education and medical monitoring,
      but it can improve well-being and delay the need for lung transplantation.

PMID- 10200859
TI  - Nelfinavir mesylate: a protease inhibitor.
AB  - OBJECTIVE: To review the clinical pharmacology, pharmacokinetics, efficacy,
      adverse effects, drug interactions, and dosage guidelines of nelfinavir mesylate.
      DATA SOURCE: A MEDLINE search restricted to English-language literature from
      January 1966 to February 1998 and an extensive review of journals was conducted
      to prepare this article. MeSH headings included protease inhibitors, nelfinavir
      mesylate, and AG1343. Abstracts presented at meetings and data submitted to the
      Food and Drug Administration (FDA) were also reviewed. DATA EXTRACTION: The data
      on efficacy, pharmacokinetics, adverse effects, and drug interactions were
      obtained from in vitro studies, as well as open-label and controlled trials. DATA
      SYNTHESIS: Nelfinavir inhibits HIV protease enzyme resulting in formation of
      immature and noninfectious virions. In combination with nucleoside reverse
      transcriptase inhibitors, nelfinavir is effective in reducing the viral load
      below the quantifiable limit (< 500 copies/mL) and increasing the mean CD4+ cell
      count. This antiviral effect is sustained at least over 21 months. The
      bioavailability of nelfinavir ranges from 20% to 80%, and it increases when
      nelfinavir is administered with food. Following multiple dosing of nelfinavir 750
      mg three times daily, maximum concentration at steady-state was 3-4 micrograms/mL
      and minimum concentration was 1-3 micrograms/mL. The elimination half-life for
      nelfinavir ranges from three to five hours. Nelfinavir is primarily metabolized
      in the liver by the cytochrome P450 isoenzymes and excreted in the feces. Current
      dosing recommendations are 750 mg three times daily for adults and adolescents
      and 20-30 mg/kg/dose three times daily for children aged 2-13 years. Studies of
      twice-daily regimens in adults are being conducted and are promising. Use of
      nelfinavir as salvage therapy is also being studied. Some of the commonly
      reported adverse events of nelfinavir are diarrhea, nausea, vomiting, and
      abdominal pain. CONCLUSIONS: Despite the limited published data, the FDA has
      approved nelfinavir in combination therapy for the treatment of HIV infection.
      The choice of antiretroviral (ARV) regimens should be made based on the risk of
      disease progression as indicated by HIV RNA concentrations and CD4+ cell counts,
      patients' previous ARV experiences and responses, concomitant drug therapy,
      compliance history, underlying disease states, and adverse reaction history.

PMID- 10200861
TI  - Glutamine supplementation in catabolic patients.
AB  - OBJECTIVE: To evaluate the safety and efficacy of parenteral and enteral
      glutamine supplementation in patients who are catabolic. DATA SOURCES: English
      language clinical trials and review articles identified by MEDLINE searches
      (January 1970-December 1997) and from bibliographies of selected articles were
      considered for possible inclusion. Key words used in the search strategy were
      glutamine, critical illness, stress, catabolism, injury, enteral nutrition, and
      parenteral nutrition. STUDY SELECTION AND DATA EXTRACTION: Inclusion was
      restricted to pertinent studies that evaluated the safety of glutamine
      supplementation, as well as effects of glutamine on amino acid metabolism, immune
      function, and patient outcome. Data from 18 clinical trials and multiple review
      articles were compiled into a review format. DATA SYNTHESIS: Glutamine is an
      important metabolic fuel for intestinal enterocytes, lymphocytes and macrophages,
      and metabolic precursors such as purines and pyrimidines. Although originally
      considered a nonessential amino acid, experimental work suggests that glutamine
      is essential for maintaining intestinal function, immune response, and amino acid
      homeostasis during periods of severe stress. In the past decade, clinical trials
      conducted in metabolically stressed patients indicate that glutamine improves
      nitrogen balance, increases cellular proliferation, decreases the incidence of
      infection, and shortens hospital stay in some catabolic patients. CONCLUSIONS:
      Glutamine has been studied extensively over the past decade for its role during
      critical illness. Clinical trials conducted in humans demonstrate glutamine to be
      well tolerated without adverse consequences, even during times of stress.
      Although glutamine has shown promise in select groups of catabolic patients,
      additional studies are needed to define which patient populations derive the
      greatest benefit from supplemental glutamine and the mechanisms by which these
      effects are exerted.

PMID- 10200862
TI  - Home blood glucose monitoring.
AB  - OBJECTIVE: To provide a review of self-monitoring blood glucose including home
      blood glucose meters and patient education. DATA SOURCES: A MEDLINE search
      (January 1966-January 1998) was conducted to identify original and review
      articles. Search terms included self-monitoring blood glucose and blood glucose
      monitoring. Owner's manuals and package inserts were reviewed to determine
      specific characteristics for each glucose meter. DATA EXTRACTION: All current
      original and review articles about self-monitoring blood glucose and home blood
      glucose meters were included if they contained information about benefits of self
      monitoring blood glucose, technology and performance of blood glucose meters,
      quality control, selection characteristics of blood glucose meters, and patient
      education. DATA SYNTHESIS: Self-monitoring of blood glucose has become an
      increasingly vital component of the care of the diabetic patient. Many glucose
      monitors are available with various features that may be confusing to
      pharmacists. Pharmacists need to be able to aid patients in the selection of an
      appropriate glucose meter and provide the education necessary for proper use and
      follow-up. Patient education is a key component in optimizing the potential
      benefits of self-monitoring. CONCLUSIONS: Self-monitoring of blood glucose, if
      used properly, can have a positive effect by increasing patient involvement in
      overall diabetes care. Pharmacists are accessible and can teach patients
      necessary skills that will enhance their ability to self-manage blood glucose.

PMID- 10200863
TI  - A critical review of selected pharmacoeconomic analyses of antidepressant
      therapy.
AB  - OBJECTIVE: To evaluate the pharmacoeconomic benefits of treating depression and
      compare the available therapies by reviewing the current literature on economic
      analyses of depression. DATA SOURCES: A MEDLINE search (January 1966-June 1998)
      of English-language literature relating to economic analyses of depression was
      conducted. Key search terms included depression, antidepressant, economics,
      pharmacoeconomics, outcomes, and costs. Additional literature was collected from
      reference lists of articles found through the MEDLINE search. STUDY SELECTION AND
      DATA EXTRACTION: A MEDLINE search was performed using the above key words. Search
      and evaluation were limited to pharmacoeconomic evaluations of major depressive
      disorder. All available studies were considered for inclusion in the review. DATA
      SYNTHESIS: The advent of newer, brand-name antidepressants as well as increased
      concern regarding healthcare costs has raised interest in the costs associated
      with treating depression. Although the selective serotonin-reuptake inhibitors
      (SSRIs) and other newer antidepressants have higher acquisition costs, both
      modeling and naturalistic studies have shown that the total cost of treating
      depression is no higher with SSRIs than with the tricyclic antidepressants. These
      differences are primarily due to increased patient adherence with the newer
      agents and lower costs secondary to physician visits, laboratory monitoring, and
      hospitalization. CONCLUSIONS: The economic aspects of treating depression are
      becoming more frequently evaluated as newer antidepressant medications become
      available and as healthcare entities attempt to address increasing costs. In
      general, most pharmacoeconomic research on depression has been conducted on one
      of the SSRIs in comparison with various tricyclic antidepressants. These studies
      frequently use simulation techniques and rely heavily on data from clinical
      trials. Few studies have compared the newer antidepressants, and no clear
      evidence exists that any one of these agents is more cost-effective than others.
      Even fewer studies have addressed the pharmacoeconomics of medication management
      of depression in various healthcare environments (e.g., public mental health care
      vs. private psychiatry vs. primary care).

PMID- 10200864
TI  - Risk of latex allergy from medication vial closures.
AB  - A latex allergy, like all allergies, is a serious matter that requires special
      precautions on behalf of patients and healthcare workers. The FDA final rule on
      the labeling of natural rubber-containing medical devices will assist in the
      creation of a latex-safe environment for latex-sensitive individuals. Currently,
      this ruling does not apply to medication vial closures that contain latex. Until
      further action by the FDA, the only way to determine whether a medication vial
      closure contains latex is by directly contacting the pharmaceutical manufacturer.
      Moreover, in order to rule whether special labeling should be mandatory for latex
      containing medication vials, additional evidence is needed to clarify whether
      exposure to trace amounts of latex from a medication vial stopper can cause
      allergic reactions in individuals who are sensitive to latex.

PMID- 10200865
TI  - Interaction of ACE inhibitors and aspirin in patients with congestive heart
      failure.
AB  - The beneficial effects of aspirin and ACE inhibitors in CHF have been well
      established; however, the clinical relevance of the drug interaction between
      these agents remains controversial. The exact mechanism of this interaction is
      not known, but the proposed theory involves the opposing effects of aspirin and
      ACE inhibitors on prostaglandins. The medical literature dose not provide a clear
      picture of the clinical significance of concomitant aspirin and ACE inhibitor
      therapy. Some studies suggest that the dose of aspirin may influence the clinical
      relevance of this interaction. Short-term use of aspirin > or = 300 mg was found
      to attenuate enalapril's effect on hemodynamic variables. However, short-term use
      of low-dose aspirin (236 mg) produced no effect on blood pressure. Patients with
      CHF who require therapy with both aspirin and ACE inhibitors may want to consider
      low doses of aspirin with active monitoring of hemodynamic parameters. However,
      chronic aspirin therapy in patients with CHF on concomitant ACE inhibitors has
      not been adequately studied at this time. Data concerning a possible interaction
      between angiotensin II receptor antagonists and aspirin are not available.
      However, because angiotensin II receptor antagonists do not interfere with
      kininase II activity, it would seem unlikely that aspirin would interact
      similarly with an angiotensin II receptor antagonist. Further studies are needed
      to examine the exact mechanism of the interaction between aspirin and ACE
      inhibitors. These studies should focus on the effects of different doses of
      aspirin given concomitantly with ACE inhibitors in patients with CHF.
      Prospective, randomized studies are also needed to determine the long-term
      effects of aspirin and ACE inhibitor therapy on mortality in patients with CHF.

PMID- 10200866
TI  - Fatal Stevens-Johnson syndrome in an AIDS patient treated with sulfadiazine.

PMID- 10200867
TI  - Risperidone-induced mania.

PMID- 10200868
TI  - Acute liver damage possibly related to sertraline and venlafaxine ingestion.

PMID- 10200869
TI  - Acute dystonia associated with fluvoxamine-metoclopramide.

PMID- 10200870
TI  - Elevation of serum creatinine following fosinopril therapy.

PMID- 10200871
TI  - Disruption of vanS by IS1216V in a clinical isolate of Enterococcus faecium with
      VanA glycopeptide resistance.

PMID- 10200872
TI  - Lack of ritonavir antifungal effect in vitro.

PMID- 10200873
TI  - A turning of the page.

PMID- 10200874
TI  - Overpopulation of small animal veterinarians on Prince Edward Island.

PMID- 10200875
TI  - The CAHI versus the BVD.

PMID- 10200876
TI  - An ethicist's commentary on the case of collecting semen from a crippled bull.

PMID- 10200879
TI  - To litigate or mediate, that is the question!

PMID- 10200880
TI  - The effect of vaccines and antimicrobials on the formation of injection site
      lesions in subprimals of experimentally injected beef calves.
AB  - Two hundred and thirty-nine beef calves were used to determine the occurrence of
      injection site lesions at slaughter (16 to 17 mo of age) following the use of 3
      different 8-way clostridial bacterins, a 4-way viral respiratory vaccine, various
      long-acting oxytetracycline preparations, florfenicol, ceftiofur, and
      trimethoprim-sulfa when injected in the top hip (top butt), thigh (round), or
      neck (blade) of calves at 2 to 3 or 5 to 7 mo of age. The occurrence of lesions
      varied by product, route of administration, and location of injection. The number
      of steaks affected with lesions, the trim weight of lesions, the histological
      class of lesions, and the economic losses from trim are described.

PMID- 10200881
TI  - Survey of Fascioloides magna in farmed wapiti in Alberta.
AB  - The formalin-ethyl acetate sedimentation procedure was used to detect ova of the
      giant liver fluke, Fascioloides magna, in feces of farmed wapiti in Alberta.
      Twenty (3.2%) of the 629 fecal samples examined contained ova of F. magna.
      Thirteen (33.3%) of the 39 farms surveyed had wapiti positive for F. magna. The
      presence of F. magna in farmed wapiti north of the North Saskatchewan River is
      confirmed, and 3 areas where the infection has become endemic are identified.

PMID- 10200882
TI  - Analyte comparisons between 2 clinical chemistry analyzers.
AB  - The purpose of this study was to assess agreement between a wet reagent and a dry
      reagent analyzer. Thirteen analytes (albumin, globulin, alkaline phosphatase,
      alanine aminotransferase, amylase, urea nitrogen, calcium, cholesterol,
      creatinine, glucose, potassium, total bilirubin, and total protein) for both
      canine and feline serum were evaluated. Concordance correlations, linear
      regression, and plots of difference against mean were used to analyze the data.
      Concordance correlations were excellent for 8 of 13 analytes (r > or = 0.90); the
      correlations for albumin, potassium, and calcium were clinically unreliable. The
      linear regression analysis revealed that several analytes had slopes
      significantly different from unity, which was likely related to methodological
      differences. Compared to the wet reagent analyzer, the dry reagent analyzer
      showed excellent agreement for alkaline phosphatase, alanine aminotransferase,
      amylase (feline), urea nitrogen, cholesterol, creatinine, glucose, total
      bilirubin (canine), and total protein. However, it showed only slight to
      substantial agreement for amylase (canine), calcium, albumin, potassium, and
      total bilirubin (feline).

PMID- 10200883
TI  - Preputial prolapse in an alpaca.

PMID- 10200884
TI  - [Monitoring of microbial contamination of stick wound in swine carcasses].
AB  - This study was done to evaluate the microbial contamination by Salmonella spp.,
      Escherichia coli, fecal coliforms, and total aerobic count of the stick wound of
      swine carcasses. The effectiveness of trimming the stick wound in the 2 Quebec
      slaughterhouses visited was evaluated. A bacteriological analysis was done on 276
      stick wounds. Results indicated that, before trimming, 0.9% stick wounds were
      contaminated by Salmonella spp. Contamination by coliforms was observed in 40.6%
      of samples, and 27.7% were positive for E. coli. After trimming the stick wounds,
      1.1% were contaminated by Salmonella spp., 34.1% were contaminated by coliforms,
      and 26.2% were positive for E. coli. The results showed that trimming contributes
      to reducing significantly the bacterial total count at the site and that the
      bacterial load at this site was less important than that found on the brisket.

PMID- 10200885
TI  - Clomipramine-induced urinary retention in a cat.
AB  - A 10-year-old, female, spayed shorthair with presumed psychogenic alopecia was
      treated with clomipramine (1 mg/kg body weight/day). The cat developed urinary
      retention within 2 days. Clomipramine was discontinued. Clinical signs resolved
      over the next 7 days. The urinary retention was attributed to the anticholinergic
      effects of clomipramine.

PMID- 10200886
TI  - Observations on the use of tetracycline and niacinamide as antipruritic agents in
      atopic dogs.
AB  - Tetracycline and niacinamide were administered in combination to 19 atopic dogs
      to determine their effectiveness in controlling pruritus. The pruritus was
      controlled successfully in only one dog. One dog experienced diarrhea that was
      severe enough to warrant stopping the medication.

PMID- 10200887
TI  - Immunodeficiency syndrome in a 3-year-old llama.
AB  - An adult, castrated male llama was presented for evaluation of a chronic
      respiratory problem. Complete blood analyses indicated a leukopenia and
      hypoproteinemia. Radial immunodiffusion, bone marrow core, and lymph node
      biopsies supported a tentative diagnosis of juvenile llama immunodeficiency
      syndrome. This diagnosis was confirmed by postmortem findings.

PMID- 10200888
TI  - Distribution of Streptococcus suis capsular types in 1998.

PMID- 10200890
TI  - Early autonomic dysfunction in patients with diabetes mellitus assessed by
      spectral analysis of heart rate and blood pressure variability.
AB  - Patients with diabetes mellitus (DM) often have alterations of the autonomic
      nervous system (ANS), even early in their disease course. Previous research has
      not evaluated whether these changes may have consequences on adaptation
      mechanisms in DM, e.g. to mental stress. We therefore evaluated whether patients
      with DM who already had early alterations of the ANS reacted with an abnormal
      regulatory pattern to mental stress. We used the spectral analysis technique,
      known to be valuable and reliable in the investigation of disturbances of the
      ANS. We investigated 34 patients with DM without clinical evidence of ANS
      dysfunction (e.g. orthostatic hypotension) and 44 normal control subjects (NC
      group). No patients on medication known to alter ANS responses were accepted. The
      investigation consisted of a resting state evaluation and a mental stress task
      (BonnDet). In basal values, only the 21 patients with type 2 DM were different in
      respect to body mass index and systolic blood pressure. In the study parameters
      we found significantly lower values in resting and mental stress spectral power
      of mid-frequency band (known to represent predominantly sympathetic influences)
      and of high-frequency and respiration bands (known to represent parasympathetic
      influences) in patients with DM (types 1 and 2) compared with NC group (5.3 +/-
      1.2 ms2 vs. 6.1 +/- 1.3 ms2, and 5.5 +/- 1.6 ms2 vs. 6.2 +/- 1.5 ms2, and 4.6 +/-
      1.7 ms2 vs. 6.2 +/- 1.5 ms2, for resting values respectively; 4.7 +/- 1.4 ms2 vs.
      5.9 +/- 1.2 ms2, and 4.6 +/- 1.9 ms2 vs. 5.6 +/- 1.7 ms2, and 3.7 +/- 2.1 ms2 vs.
      5.6 +/- 1.7 ms2, for stress values respectively; M/F ratio 6/26 vs. 30/14). These
      differences remained significant even when controlled for age, sex, and body
      weight. However, patients with DM type 2 (and significantly higher body weight)
      showed only significant values in mental stress modulus values. There were no
      specific group effects in the patients with DM in adaptation mechanisms to mental
      stress compared with the NC group. These findings demonstrate that power spectral
      examinations at rest are sufficiently reliable to diagnose early alterations in
      ANS in patients with DM. The spectral analysis technique is sensitive and
      reliable in investigation of ANS in patients with DM without clinically
      symptomatic autonomic dysfunction.

PMID- 10200889
TI  - Evidence for circovirus in cattle with respiratory disease and from aborted
      bovine fetuses.

PMID- 10200891
TI  - A fractal approach for evaluation of pulmonary circulation in man at rest and
      during exercise.
AB  - Changes in pulmonary circulation caused by muscular exercise and body position
      are usual in daily life. By using first-pass radiocardiography and fractal
      analysis, pulmonary circulation in man was evaluated at rest and during muscular
      exercise. At rest, pulmonary circulation was heterogeneous as described by the
      relative dispersion (which is the coefficient of variation, i.e. the standard
      deviation of the pulmonary transit times divided by the mean transit time; RD =
      0.51 +/- 0.06) and fractal in nature. During exercise, pulmonary circulation
      became more homogeneous (RD = 0.35 +/- 0.04; P < 0.001). The calculated fractal
      dimension decreases from 1.09 at rest to 1.06 during exercise. The model
      identifies a cubic-law response for circulation heterogeneity and a quarter-power
      law for resistance during muscular exercise.

PMID- 10200892
TI  - Cardiovascular response during head-up tilt in chronic fatigue syndrome.
AB  - This study examined the cardiovascular response to orthostatic challenge, and
      incidence and mechanisms of neurally mediated hypotension in chronic fatigue
      syndrome (CFS) during a head-up tilt test. Stoke volume was obtained by a
      thoracic impedance cardiograph, and continuous heart rate and blood pressure were
      recorded during a 45-min 70 degrees head-up tilt test. Thirty-nine CFS patients
      and 31 healthy physically inactive control subjects were studied. A positive
      tilt, i.e. a drop in systolic blood pressure of > 25 mmHg, no concurrent increase
      in heart rate and/or development of presyncopal symptoms, was seen in 11 CFS
      patients and 12 control subjects (P > 0.05). During baseline and the first 5 min
      of head-up tilt, CFS patients had higher heart rate and smaller pulsatile
      systolic area than control subjects (P < 0.05). Among subjects who completed the
      test, those with CFS had higher heart rate and smaller stroke volume (P < 0.05)
      than corresponding control subjects. When comparing those who had a positive test
      outcome in each group, CFS patients had higher heart rates and lower pulse
      pressure and pulsatile-systolic areas during the last 4 min before being returned
      to supine (P < 0.05). These data show that there are baseline differences in the
      cardiovascular profiles of CFS patients when compared with control subjects and
      that this profile is maintained during head-up tilt. However, the frequency of
      positive tilts and the haemodynamic adjustments made to this orthostatic
      challenge are not different between groups.

PMID- 10200893
TI  - Wall motion abnormalities in male elite orienteers are aggravated by exercise.
AB  - During the period 1979-92, 16 (15 men and one woman) sudden unexpected cardiac
      deaths occurred among young Swedish orienteers. This finding indicated a sharp
      increase in the death rate of orienteers, and necropsy demonstrated that
      myocarditis was a common histopathological finding. Therefore, an extensive non
      invasive cardiac investigation was performed. A total of 59 male elite orienteers
      (mean age 23 years) and 36 cross-country skiers and middle-distance runners (mean
      age 22 years), serving as controls, were examined by both echocardiography at
      rest and radionuclide ventriculography at rest and during exercise. Wall motion
      abnormalities were found in eight orienteers using echocardiography. The purpose
      of this study was to examine whether the group of orienteers with wall motion
      abnormalities found using echocardiography had a smaller increase in ejection
      fraction from rest to exercise using radionuclide ventriculography than the rest
      of the orienteers and the controls, indicating an aggravation of the wall motion
      abnormalities during exercise. There were no significant differences in the
      ejection fraction at rest between the groups. In the orienteers with wall motion
      abnormalities (group 1), 62% (five out of eight) had less than a 0.05 unit
      increase in left ventricular ejection fraction compared with 27% (14 out of 51)
      of the remaining orienteers (group 2) and 19% (7 out of 36) of the controls
      (group 3). A comparison of athletes in group 1 with those in groups 2 and 3
      combined revealed a statistically significant difference (P < 0.05). The
      divergent response in left ventricular ejection fraction during exercise suggests
      an aggravation of the wall motion abnormalities with exercise. Both the
      echocardiographic and the radionuclide ventriculographic findings indicate that
      the orienteers in group 1 had concealed left ventricular damage.

PMID- 10200894
TI  - Reduced cardiac sympathetic autonomic tone after long-term nasal continuous
      positive airway pressure in obstructive sleep apnoea syndrome.
AB  - The increased sympathetic activation that occurs in obstructive sleep apnoea
      (OSA) may play an important role in associated morbidity. We investigated the
      effect of long-term (3 month) nasal continuous positive airway pressure (CPAP) on
      the autonomic nervous system assessed by heart rate variability (HRV). Fourteen
      patients (12 men), mean age 61.4 +/- 8.1 years, with OSA underwent continuous
      synchronized electrocardiographic and polysomnographic monitoring. The
      apnoea/hypopnoea index (AHI) decreased from 50.6 +/- 13.7 to 2.2 +/- 2.5 events h
      1 after CPAP. HRV analysis showed significant decreases in low frequency (LF;
      from 7.12 +/- 1.06 to 6.22 +/- 1.18 ln ms2 Hz-1; P < 0.001), high frequency (HF;
      from 5.91 +/- 0.87 to 5.62 +/- 0.92 ln ms2 Hz-1; P < 0.05) and LF/HF (from 1.21
      +/- 0.12 to 1.11 +/- 0.15 ln ms2 Hz-1; P < 0.001) when the patients were asleep.
      The decrease in LF/HF was prolonged into the daytime (from 1.33 +/- 0.22 to 1.24
      +/- 0.21 ln ms2 Hz-1; P < 0.001). Treatment of OSA by CPAP significantly reduced
      the parameters of cardiac sympathetic tone, a favourable effect.

PMID- 10200895
TI  - Altered skeletal muscle glucose transport and blood lipid levels in habitual
      cigarette smokers.
AB  - We determined whether habitual cigarette smoking alters insulin-stimulated
      glucose transport and GLUT4 protein expression in skeletal muscle. Vastus
      lateralis muscle was obtained from 10 habitual cigarette smokers and 10 control
      subjects using an open muscle biopsy procedure. Basal 3-O-methylglucose transport
      was twofold higher (P < 0.01) in muscle from habitual smokers (0.05 +/- 0.08 vs.
      1.04 +/- 0.19 mumol ml-1 h-1; controls vs. smokers respectively). Insulin (600
      pmol l-1) increased glucose transport 2.6-fold (P > 0.05) in muscle from control
      subjects, whereas no significant increase was noted in habitual smokers. Skeletal
      muscle GLUT4 protein expression was similar between the groups. FFA levels were
      elevated in the smokers (264 +/- 49 vs. 748 +/- 138 mumol l-1 for control
      subjects vs. smokers; P < 0.05), and serum triglyceride levels were increased in
      the smokers (0.9 +/- 0.2 vs. 2.3 +/- 0.6 mmol l-1 for control subjects vs.
      smokers; P < 0.05). Skeletal muscle carnitine palmitil (acyl) transferase
      activity was similar between the groups, indicating that FFA transport into the
      mitochondria was unaltered by cigarette smoking. In conclusion, cigarette smoking
      appears to have a profound effect on glucose transport in skeletal muscle. Basal
      glucose transport is markedly elevated, whereas insulin-stimulated glucose
      transport is impaired. These changes cannot be explained by altered protein
      expression of GLUT4, but may be related to increased serum FFA and triglyceride
      levels. These findings highlight the importance of identifying habitual cigarette
      smokers in studies aimed at assessing factors that lead to alterations in lipid
      and glucose homeostasis in people with non-insulin-dependent diabetes mellitus
      (NIDDM).

PMID- 10200896
TI  - Effect of beta blockade with and without sympathomimetic activity (ISA) on
      sympathovagal balance and baroreflex sensitivity.
AB  - Beta blockers increase heart rate variability (HRV) and improve survival in
      coronary artery disease (CAD). The benefit of beta blockers with intrinsic
      sympathomimetic activity (ISA) in CAD still remains a matter of debate, and their
      effect on HRV has not yet been investigated. Therefore, we measured HRV, systolic
      blood pressure variability (BPV) and baroreflex sensitivity (BRS) under
      propranolol (PROP, without ISA, 160 mg q.d.), pindolol (PIN, with potent ISA, 15
      mg q.d.) and placebo (PLA, q.d.) in 30 healthy subjects, aged 21-39 years, during
      controlled frequency breathing (0.30 Hz) in supine and tilt positions. PROP
      increased HRV in the high-frequency (0.15-0.40 Hz) band (PROP 7.4 +/- 1.0; PLA
      6.9 +/- 1.4; PIN 6.8 +/- 1.0 ln MI2; P = 0.003), decreased BPV in the low
      frequency band (at 0.1 Hz, Mayer waves) (PROP 0.6 +/- 0.7; PLA 1.3 +/- 1.1; PIN
      1.2 +/- 1.2 ln mmHg2; P = 0.001) and enhanced BRS (PROP 14.6 +/- 9.5; PLA 8.0 +/-
      6.8; PIN 8.7 +/- 6.8 ms mmHg-1; P = 0.001) in the supine position. After passive
      tilt, PROP decreased HRV in the low-frequency band (PROP 6.1 +/- 0.9; PLA 6.5 +/-
      1.1; PIN 6.9 +/- 0.7 ln MI2; P < 0.001) and decreased Mayer waves (PROP 1.8 +/-
      0.8; PLA 2.4 +/- 1.0; PIN 2.7 +/- 0.8 ln mm Hg2; P < 0.001). PIN increased the
      low-frequency HRV response, which is induced by passive tilt (PIN + 0.9 +/- 1.0;
      PLA + 0.3 +/- 1.3, PROP + 0.3 +/- 1.0 ln MI2; P = 0.026). Our results prove that
      beta-adrenergic blockade with potent ISA does not increase HRV, has no beneficial
      effect on autonomic balance and even exaggerates sympathetic responses to passive
      tilt.

PMID- 10200897
TI  - Influence of gender on the sympathetic neural adjustments to alterations in
      systemic oxygen levels in humans.
AB  - The purpose of this investigation was to determine whether gender influences the
      muscle sympathetic nerve activity (MSA) and systemic cardiovascular adjustments
      to alterations in systemic oxygen levels. To accomplish this, we performed direct
      (intraneural) measurements of muscle sympathetic nerve activity in 11 male and
      seven female young healthy adults during room air breathing, moderate isocapnic
      hypoxaemia and hyperoxaemia. During hypoxaemia, arterial oxygen saturation
      declined similarly in men and women. The magnitudes of the peak increases in MSA
      and stimulus-response 'gain' were not different between groups. However, the
      women had a shorter latency of response (P < 0.05). Women also demonstrated a
      greater increase in heart rate and a modest elevation in diastolic blood
      pressure, whereas the ventilatory responses were identical in the two groups.
      During normoxic recovery, MSA returned to baseline more quickly in women than in
      men (P < 0.05). During hyperoxaemia, muscle sympathetic nerve activity decreased
      only in the men (P < 0.05). Heart rate decreased slightly (P < 0.05) in both men
      and women, whereas blood pressure and minute ventilation were unchanged from
      normoxic control levels. Our findings fail to support an effect of gender on the
      peak muscle sympathetic nerve activity response to moderate isocapnic hypoxaemia
      in healthy young adult humans, although women demonstrate a shorter latency for
      sympathoexcitation and recovery under these conditions. In response to
      hyperoxaemia, women fail to demonstrate the sympathoinhibition consistently
      observed in men, possibly because of the low resting levels of MSA characteristic
      of young adult women. Thus, gender appears to contribute to the interindividual
      variability in sympathetic and cardiovascular responses to alterations in
      systemic oxygen levels.

PMID- 10200898
TI  - Day-to-day variation in oxygen consumption and energy expenditure during
      submaximal treadmill walking in female adolescents.
AB  - The day-to-day variation in oxygen consumption (VO2) and energy expenditure (EE)
      during horizontal treadmill walking was measured using indirect calorimetry in 20
      female adolescents (mean age 17.3 years). Two different walking speeds were used:
      5 km h-1 and an individually convenient speed of 3.0 km h-1 (mean). The two sets
      of measurements were performed on 2 consecutive days, and great care was taken to
      minimize possible disturbing factors. The mean VO2 was 919 ml min-1 at 5 km h-1
      and 622 ml min-1 at the individual speed, and the mean values of EE were 4.5 kcal
      min-1 and 3.1 kcal min-1 respectively. The individual day-to-day variation in VO2
      (at 5 km h-1) was between -11.7% and +12.6% of the mean VO2. The coefficient of
      variation (CV) was 6.4% when values were calculated in ml min-1 kg-1. The energy
      expenditure varied somewhat less between the 2 days (CV = 5.7%). The
      corresponding value for EE when walking at the individual speed was 7.2%, and the
      mean day-to-day variation in VO2 was 7.5% (CV). The rate of perceived exertion
      according to Borg's scale was lower on day 2 (11.9) compared with day 1 (13.0)
      when walking at 5 km h-1. There was no difference in heart rate between the 2
      days. It is concluded that EE varies somewhat less than VO2 on successive days,
      probably because of an interchangeable relationship between breathing gases,
      depending on which substrate is used for combustion. When using VO2 and EE for
      evaluation of physical capacity, the day-to-day variation in the measurements
      must be taken into consideration.

PMID- 10200899
TI  - Reproducibility of the alterations in circulation and cerebral oxygenation from
      supine rest to head-up tilt.
AB  - Cardiovascular stability, as affected by several diseases, may be assessed by
      head-up tilt testing. Follow-up studies are essential in both evaluating
      interventions and assessing progression. However, data on the reproducibility of
      the changes in circulatory status and cerebral oxygenation provoked by head-up
      tilt testing are fundamental to follow-up studies. The aim of this study was,
      therefore, to assess the reproducibility of the alterations in stroke volume
      (SV), mean arterial pressure (MAP), as well as oxygenated ([O2Hb]) and
      deoxygenated haemoglobin ([HHb]) concentration in cerebral tissue from supine
      rest (SUP) to head-up tilt (HUT). SV was calculated by Modelflow, a pulse contour
      method, from the finger arterial pressure wave measured by Portapres, the
      portable version of Finapres. [O2Hb] and [HHb] were measured using near-infrared
      spectroscopy (NIRS). Ten healthy individuals visited the laboratory on two
      different days. On both days, they underwent 10 min SUP followed by 10 min 70
      degrees HUT twice. SV decreased, which was (in part) compensated for by an
      increased heart rate, while MAP increased slightly during HUT compared with SUP.
      Although [HHb] increased during HUT, no presyncope symptoms were experienced. The
      circulatory variables (SV, HR and MAP) as well as [HHb] showed an acceptably
      small systematic and random error as well as reproducibility error compared with
      the observed difference between HUT and SUP and were similar between and within
      visits. Therefore, it is concluded that MAP measured by Portapres and SV
      calculated by Modelflow as well as HHb measured by NIRS seem to be reproducible
      and may therefore be used in follow-up studies.

PMID- 10200900
TI  - Twenty-four-hour cortisol response to multiple daily exercise sessions of
      moderate and high intensity.
AB  - The aim of this study was to characterize and describe the cortisol responses in
      athletes over a 24-h period on different days involving multiple exercise
      sessions of varied intensity. Seventeen endurance athletes volunteered to undergo
      three experimental treatment conditions: (a) a control day involving no exercise;
      (b) an exercise day with two sessions of high-intensity exercise; and (c) an
      exercise day with two sessions of moderate-intensity exercise. Significant
      changes (P < 0.01) were found owing to the influence of both types of exercise
      during the daytime (high-intensity exercise producing a greater cortisol response
      than moderate intensity). At night after the moderate-intensity exercise (at
      selected times), cortisol response was significantly less than during the control
      condition at corresponding times (P < 0.05). After high-intensity exercise (at
      selected times), cortisol levels were significantly less (P < 0.05) than in the
      control condition at corresponding times. Additionally, certain night-time
      responses after the high-intensity exercise were significantly less than the
      moderate-intensity exercise responses at similar time points. The results
      indicate that daytime multiple exercise sessions produce suppressed cortisol
      levels at night, and the magnitude of this effect is dependent upon the intensity
      at which the daytime exercise is performed. The physiological mechanism inducing
      this effect upon cortisol levels at night is unclear from the present data.

PMID- 10200901
TI  - Adaptive responses of human skeletal muscle to vibration exposure.
AB  - The aim of this study was to investigate the effects of whole-body vibrations
      (WBV) on the mechanical behaviour of human skeletal muscle. For this purpose, six
      female volleyball players at national level were recruited voluntarily. They were
      tested with maximal dynamic leg press exercise on a slide machine with extra
      loads of 70, 90, 110 and 130 kg. After the testing, one leg was randomly assigned
      to the control treatment (C) and the other to the experimental treatment (E)
      consisting of vibrations. The subjects were then retested at the end of the
      treatment using the leg press. Results showed remarkable and statistically
      significant enhancement of the experimental treatment in average velocity (AV),
      average force (AF) and average power (AP) (P < 0.05-0.005). Consequently, the
      velocity-force and power-force relationship shifted to the right after the
      treatment. In conclusion, it was affirmed that the enhancement could be caused by
      neural factors, as athletes were well accustomed to the leg press exercise and
      the learning effect was minimized.

PMID- 10200902
TI  - Pulmonary hypertension in collagen vascular disease.
AB  - Pulmonary hypertension associated with collagen vascular disease often eludes
      diagnosis, sometimes causing considerable morbidity or even death before being
      identified. This review details its characteristic clinical features, appropriate
      diagnostic and treatment approaches, and expected outcomes.

PMID- 10200903
TI  - Fertility-sparing treatment of patients with ovarian cancer.
AB  - Ovarian malignancies in reproductive age women often provide the physician and
      patient with a management dilemma. Many investigators have proposed conservative
      management in early-stage disease. This article provides evidence supporting
      fertility-sparing management in young women with early ovarian malignancies.

PMID- 10200904
TI  - Preventing sudden death in student athletes.
AB  - Cardiac death in athletes younger than 35 is almost always associated with
      congenital malformations, of which hypertrophic cardiomyopathy is most common.
      This article proposes a screening history and physical examination for these
      conditions.

PMID- 10200905
TI  - Gonococcal arthritis.
AB  - A high index of clinical suspicion; careful culturing of samples from blood,
      endocervix, urethra, pharynx, skin, synovial fluid and tissue, and rectum; and
      appropriate antibiotic therapy will rapidly control and prevent more serious
      complications of disseminated gonococcal infection.

PMID- 10200906
TI  - Colorectal carcinoma: etiology, diagnosis, and screening.
AB  - Colorectal carcinoma is a leading cause of death in the United States. Risk
      factors include genetic predisposition, diet, obesity, and inflammatory bowel
      disease. Early detection and chemoprevention can lead to a lower death rate.
      Future developments will include sensitive and specific large-scale screening.

PMID- 10200907
TI  - The mind-heart connection in coronary artery disease.
AB  - Mind and heart are connected by neurocardiologic pathways. Psychosocial risk
      factors produce sympathetic activation, resulting in mortality in coronary artery
      disease. Aspirin, exercise, and psychosocial and spiritual supports are important
      resources in protecting the heart against these risk factors.

PMID- 10200908
TI  - Gene expression during vascular pericyte differentiation.
AB  - Pericytes, an integral part of the microvasculature, are involved in a number of
      different processes, including angiogenesis. Many of the early studies on these
      cells are descriptive and concentrate on the location of pericytes in vivo,
      surrounding the endothelial cells in the microvessels. These studies led to the
      proposals that pericytes have a function in maintaining blood flow and contribute
      to the mechanical strength of the microvessels. However, with the advancement of
      tissue culture techniques and molecular technology it has been shown that these
      cells also have the ability to differentiate into a variety of different cell
      types, including osteoblasts, chondrocytes, adipocytes, fibroblasts, and smooth
      muscle cells. This review concentrates on the differentiation of pericytes along
      the osteogenic pathway. Pericytes behave like osteoblasts in vitro, by forming a
      mineralized matrix and expressing a number of genes that are also expressed by
      osteoblasts. These cells also form a well-defined matrix of bone, cartilage, and
      fibrous tissue in vivo, although it is not clear under what circumstances
      pericytes express osteogenic potential in situ. This review highlights the
      potential functional importance of pericytes in the growth, maintenance, and
      repair of the skeleton and in diseases involving ectopic ossification and
      calcification.

PMID- 10200909
TI  - CREB-mediated transcriptional control.
AB  - cAMP-response-element-binding protein, CREB, is a 43-kDa leucine zipper
      transcription factor identified and cloned via the study of cAMP-regulated genes.
      In the last decade, numerous studies have contributed much to our understanding
      of CREB structure, function, and CREB-mediated transcription. CREB binds to the
      cAMP-response-element (CRE) as a homodimer formed via the leucine zipper motif
      present at its C-terminus; its transcriptional activity is regulated by
      phosphorylation at Ser133, located within the N-terminal transactivation domain.
      Active, Ser133-phosphorylated CREB effects transcription of CRE-dependent genes
      via interaction with the 265-kDa co-activator protein CREB-binding-protein, CBP,
      which bridges the CRE/CREB complex to components of the basal transcriptional
      apparatus. This mechanism of CREB activation is effected by diverse signals,
      including those regulating the intracellular levels of cAMP and Ca+2, growth
      factors, and cellular stress. Accordingly, CREB-mediated transcription regulates
      diverse cellular responses, including intermediary metabolism, neuronal
      signaling, cell proliferation, and apoptosis. In addition to the regulation of
      CREB by phosphorylation, the viral oncoproteins HBV pX and HTLVI Tax regulate
      CREB transcriptional efficacy by an alternative mechanism, by increasing its DNA
      binding affinity for viral and/or cellular CRE sites. In this review I describe
      key experiments that have defined the mechanism of CREB activation, with primary
      emphasis on emerging evidence linking CREB to cellular growth and development.

PMID- 10200910
TI  - Regulation and regulatory activities of transforming growth factor beta.
AB  - Transforming growth factor beta (TGF beta) is unique among growth factors in its
      potent and widespread actions. Almost every cell in the body has been shown to
      make some form of TGF beta, and almost every cell has receptors for TGF beta.
      Therefore, it becomes apparent that this growth factor must be tightly regulated
      to prevent disease. The mechanisms of regulation of TGF beta are extensive and
      complex. One set of mechanisms centers around the fact that TGF beta is produced
      in a latent form that must be activated to produce biologically active TGF beta.
      These mechanisms include the latency of the molecule, the production of various
      latent forms, its targeting to cells for activation or to matrix for storage, and
      the means of activation of the latent forms. The TGF beta isoforms and the types,
      affinity, and signaling functions of its receptors also add complexity to the
      regulation of the effects of TGF beta. Active TGF beta regulates numerous
      processes in the body. TGF beta has three major biological effects: growth
      inhibition, stimulation of extracellular matrix formation, and immunosuppression.
      The means by which TGF beta regulates the expression of the numerous genes on
      which it has effects are complex and more information is needed. The means by
      which TGF beta regulates gene expression and the means by which the actions of
      TGF beta are regulated are addressed in this review.

PMID- 10200911
TI  - Regulation of amelogenin gene expression.
AB  - The X-chromosomal amelogenin gene is expressed at a high level by ameloblast
      cells within the enamel organ for a short time during tooth development.
      Therefore, expression is both tooth specific and developmentally regulated. A Y
      chromosomal amelogenin gene is also active in human and cow, but has not been
      detected in mouse. Genes and/or cDNAs have been cloned for mouse, human, cow,
      rat, pig, opossum, and hamster, and analyses have indicated that coding and
      upstream regions are conserved across species. Alternative splicing is extensive
      and produces as many as 9 mRNAs from the 7 exon murine gene, resulting from
      single and multiple exon skipping and alternate 3' site selection within exon 6.
      The pattern of alternative splicing varies both between species and during
      development, which is expected to result in some diversity through varying
      complements of amelogenin proteins associated with this highly conserved gene.

PMID- 10200912
TI  - Contributions of Gla and EGF-like domains to the function of vitamin K-dependent
      coagulation factors.
AB  - Blood coagulation is a response to vascular injury leading to the activation of
      platelets and coagulation factors with the ultimate formation of a fibrin plug.
      Several coagulation factors are zymogens of serine proteases that require vitamin
      K for normal biosynthesis. The active forms of these proteases and their
      cofactors form membrane-bound macromolecular complexes. In the final step
      prothrombin is activated to thrombin by active factor X in complex with its
      cofactor, factor V. Thrombin then cleaves designated peptide bonds in fibrinogen,
      resulting in the formation of fibrin monomers that polymerize to insoluble fibrin
      strands. This process is regulated by an anticoagulant counterpart, the so-called
      protein C anticoagulant system. Balance between the two systems is crucial to
      avoid bleeding on the one hand and thrombosis on the other. The coagulation and
      anticoagulation proteases, factors VII, IX, and X, and protein C, have a common
      domain structure with an N-terminal gamma-carboxyglutamic acid (Gla)-containing
      domain that is followed by two domains that are homologous to the epidermal
      growth factor (EGF), whereas the C-terminal half of each protein is occupied by a
      trypsin-like serine protease domain. Prothrombin also has an N-terminal Gla
      domain and a C-terminal serine protease domain, but they are separated by two so
      called kringle domains rather than EGF-like domains. Finally, the vitamin K
      dependent cofactor protein S has one domain with thrombin-sensitive bonds and
      four EGF-like domains in tandem between the Gla domain and a C-terminal domain
      that is homologous to plasma steroid hormone-binding proteins. The N-terminal
      noncatalytic Gla and EGF-like domains that provide the coagulation serine
      proteases with unique properties, such as affinity for certain biological
      membranes, and also mediate protein-protein interactions, are the subject of this
      review.

PMID- 10200913
TI  - Predicting peak oxygen uptake among older patients with chronic illness.
AB  - PURPOSE: To compare three equations developed to predict VO2 among patients
      diagnosed with one of two chronic diseases: essential hypertension (HTN), and
      fibromyalgia (FM). The equations included the American College of Sports Medicine
      (ACSM) equation, the FAST equation developed from the Fitness and Arthritis in
      Seniors Trial (FAST), and an equation developed by Foster et al. METHODS: One
      hundred twenty-two HTN subjects and 68 FM subjects completed a maximum exercise
      test according to the Duke/Wake Forest protocol. Measured peak VO2 was then
      compared with the VO2 predicted by the ACSM, FAST and FOSTER equations, using
      several statistical methods. RESULTS: The ACSM equation overpredicted peak VO2 in
      the HTN group by 10.0 +/- 4.0 mL/kg-1/min-1, and in the FM group by 8.6 +/- 4.9
      mL/kg-1/min-1 (P < 0.0001). The FAST equation, however, underestimated peak VO2
      by 1.5 +/- 4.2 mL/kg-1/min-1 (P < 0.01) and 1.0 +/- 3.3 mL/kg-1/min-1 (P <
      0.0001) in the HTN and FM groups, respectively. The FOSTER equation overestimated
      peak VO2 by 2.3 +/- 3.6 mL/kg-1/min-1 in the HTN group and by 2.1 +/- 3.5 mL/kg
      1/min-1 in the FM group (P < 0.0001). A large degree of variability was found for
      each of the equations. CONCLUSION: Results of this investigation indicate that
      all three equations produced peak VO2 values that were statistically different
      from measured values. Although the ACSM equation overestimated VO2 by more than 2
      metabolic equivalents (METs) in each patient group, both the FAST and FOSTER
      equations produced differences that were less than 1 MET. Further research is
      needed to examine the FAST and FOSTER equations among other patient populations
      and with other exercise protocols.

PMID- 10200914
TI  - Neuropsychological functioning among cardiac rehabilitation patients.
AB  - PURPOSE: The underlying pathophysiology contributing to coronary heart disease
      also predisposes patients to cerebrovascular disease and associated cognitive
      disorders. Although prior studies have focused on the neuropsychological sequelae
      of specific cardiac problems, few have examined the associated cognitive
      capacities and limitations of typical cardiac patients. The current study was
      designed to examine neuropsychological functioning among a sample of cardiac
      rehabilitation (CR) patients. METHODS: Using neuropsychological instruments,
      patients were compared in a CR program to age-matched outpatient control subjects
      who had no known history of cardiac or neurologic disease. Cardiac rehabilitation
      patients were then divided into dichotomous subgroups based on whether they had
      undergone coronary artery bypass grafting, had experienced a myocardial
      infarction, had hypertension, or had impaired ejection fraction.
      Neuropsychological functioning was examined relative to each of these factors.
      RESULTS: Cardiac rehabilitation patients had poorer neuropsychological test
      performance than did control subjects, with subtle relative deficits on measures
      of response generation, memory, and verbal abstraction, and particularly verbal
      fluency. Low ejection fraction, hypertension, and prior coronary artery bypass
      graft were associated with greater relative neuropsychological impairments.
      CONCLUSIONS: Although CR patients were not grossly neuropsychologically impaired
      as a group, it appears highly likely that many within a given program exhibit
      some degree of neuropsychological dysfunction. Including neuropsychological
      screening as part of pre-CR testing would help to identify such patients. This
      information may help staff to impart health care information in a manner that is
      most effective for the individual patient and may also be useful in the formation
      of realistic goals.

PMID- 10200915
TI  - The influence of short-term endurance training on the insulin blood level,
      binding, and degradation of 125I-insulin by erythrocyte receptors in patients
      after myocardial infarction.
AB  - PURPOSE: This study was directed toward establishing whether and to what extent,
      short-term endurance training influences the insulin blood level, and the binding
      and degradation of 125I-insulin by erythrocyte receptors in patients undergoing
      rehabilitation after myocardial infarction. METHODS: The study was conducted in a
      group of 60 patients who had had myocardial infarction within the past 1.5 to 3
      months and who did not have arterial hypertension and diabetes mellitus. All the
      patients took a symptom-limited cardiopulmonary exercise test. Before and after
      the test, venous blood was collected to determine lactic acid and insulin blood
      levels as well as the binding and degradation of 125I-insulin. The study group
      was randomized into two subgroups. One subgroup entered into a 3-week in-patient
      rehabilitation course. The control group was discharged from the hospital and was
      given no recommendations for physical exercise. The same investigation was
      repeated 3 weeks later. RESULTS: In the patients (50%) with hyperinsulinemia
      (insulin resistance index, > 10 microIU/mL), which was detected during the first
      investigation, insulin blood level decreased from 23.9 +/- 4.4 to 15.0 +/- 1.9
      microIU/mL (P < 0.05) after rehabilitation, whereas insulin binding increased
      from 0.67 +/- 0.05 to 0.85 +/- 0.08 pg 125I/10(11) erythrocytes (P < 0.05). In
      the control group, which included normal subjects and those with
      hyperinsulinemia, the results obtained during the first and second investigations
      showed no statistically significant changes when compared. CONCLUSIONS: The
      results suggest that a 3-week endurance training period during rehabilitation
      after myocardial infarction reduces insulin resistance in patients with
      hyperinsulinemia.

PMID- 10200916
TI  - Personality and appointment--keeping adherence in cardiac rehabilitation.
AB  - PURPOSE: Literature reviews typically have concluded that personality factors are
      unrelated to adherence to treatment programs, including adherence to exercise
      prescribed in cardiac rehabilitation. This study constitutes a reconsideration of
      this conclusion. Using the California Psychological Inventory (CPI), a well
      validated inventory of general personality tendencies, personality variables, and
      appointment-keeping in cardiac rehabilitation were examined. METHODS: Forty-nine
      men entering a cardiac rehabilitation program completed the CPI. Exercise
      capacity was measured on entry into the 4-month phase II/III program and at
      completion. Adherence indicators were appointment-keeping and completion or non
      completion of the program. General appointment-keeping and hospital admissions
      during the subsequent year were tracked. RESULTS: Appointment-keeping accounted
      for 35% of the variance in posttreatment exercise capacity, controlling for
      pretreatment exercise capacity. Scores on the CPI scales that were significantly
      related to appointment-keeping were Well-Being (perception of physical/emotional
      health), Socialization (acceptance of rules and regulations), and Communality
      (view of self as similar to others). These correlations ranged from 0.49 to 0.38.
      Those who completed the program (n = 39) had higher scores than those who did not
      (n = 10) on nearly all of the CPI scales. The differences were significant on the
      Socialization and Good Impression scales (desire for others to have a favorable
      impression of oneself). The Socialization score was correlated with keeping
      appointments in the follow-up year. CONCLUSION: Personality variables were
      associated with appointment-keeping adherence. The consistency of our results
      with those of other recent studies of personality and adherence is discussed,
      along with implications for cardiac rehabilitation.

PMID- 10200917
TI  - Dietary fat and cholesterol intake in young children compared with recommended
      levels.
AB  - PURPOSE: The National Cholesterol Education Program (1991) recommended that
      children 2 years of age or more derive less than 30% of their daily energy intake
      from total fat, less than 10% from saturated fat, up to 10% from polyunsaturated
      fat, and 10% to 15% from monounsaturated fat, and that they consume less than 300
      mg/day of cholesterol. The purpose of this study was to assess whether
      preadolescent children were following these dietary guidelines in 1994 and to
      determine the relationship of diet to obesity. METHODS: This cross-sectional
      study was performed in elementary schools in southeast Baltimore, Maryland. The
      subjects were 468 children, grades 2 through 5 (mean age, 8.9 +/- 0.8 years). The
      main outcome measures were a 24-hour diet record, body mass index, and skinfold
      thickness. RESULTS: Mean percentage of total daily energy (TDE) from fat was
      31.1%; saturated fat, 11.0%; monounsaturated fat, 10%; and polyunsaturated fat,
      4.9%. Mean dietary cholesterol was 199.1 mg/day. Although the means for total and
      saturated fat are at recommended levels, the distribution of the dietary
      responses indicates that 50% of the children exceeded these targets. Twenty-five
      percent exceeded 35% of TDE derived from fat, and 25% exceeded 13% TDE derived
      from saturated fat. Fifty percent of children consumed below the desired level of
      monounsaturated fat, and almost no children consumed the desired 10% of
      polyunsaturated fat. Although mean dietary cholesterol was at a desired level,
      16% of the children consumed more than 300 mg/day and 10% more than 377 mg/day.
      The negative correlation for sum of skinfold measurements with TDE (r = -0.14; P
      < 0.05), suggesting that fatter children consume fewer calories than thinner
      children, was the only correlate among dietary components and obesity.
      CONCLUSION: A substantial percentage of children in the United States are still
      not meeting recommended levels for dietary intake of fat and cholesterol. The
      trend for fatter children to consume fewer daily calories suggests that obesity
      is not entirely a result of overconsumption.

PMID- 10200918
TI  - Risk stratification for exercise training in cardiac patients: do the proposed
      guidelines work?
AB  - PURPOSE: Four authoritative organizations (American Association of Cardiovascular
      and Pulmonary Rehabilitation [AACVPR], the American College of Cardiology [ACC],
      the American College of Physicians [ACP], and the American Heart Association
      [AHA]) have risk stratification guidelines for supervised exercise in patients
      with cardiovascular disease. The ability of the guidelines to predict exercise
      complications is untested. METHODS: A prospective sample was evaluated that
      included 239 patients enrolled for a total of 5720 patient exercise hours in a
      phase II supervised outpatient cardiac rehabilitation exercise program between
      December 1, 1992, and June 16, 1995, who had had preprogram stress testing and/or
      left ventricular ejection fraction determination. Complications during supervised
      exercise were measured. RESULTS: Overall, 12 patients experienced complications
      during supervised exercise. None of the guidelines was predictive of
      complications (positive predictive values, 3-7%). Regression analyses
      demonstrated that current cigarette smoking was the only predictor of
      complications. There was reasonable correlation of patient risk stratification
      among the four guidelines (r = 0.19-0.47; P < 0.0001). CONCLUSIONS: Currently
      proposed exercise risk stratification guidelines are not predictive of
      complications during supervised exercise. Further work is needed before exercise
      risk stratification guidelines are used to adjudicate use of supervised services.

PMID- 10200919
TI  - What is your diagnosis? Persistent penile frenulum.

PMID- 10200920
TI  - Chronic liver disease: current concepts of disease mechanisms.
AB  - Optimal management of chronic liver disease requires an understanding of
      aetiological factors or conditions initiating and sustaining tissue damage.
      Injury may derive initially from toxin or xenobiotic exposure (direct,
      biotransformation adducts, hypersensitivity responses or immune-mediated
      mechanisms), infectious organisms, inborn errors of metabolism, or pathological
      accumulations of transition metals (iron or copper), endotoxins or
      membranocytolytic bile acids. Secondarily, cells and mediators associated with
      inflammation, pathological expression of major histocompatibility foci on
      hepatocytes and biliary epithelia, aberrant initiation of apoptosis, modification
      of the extracellular matrix, and depletion of natural antioxidants can each play
      pivotal roles. Cholestatic liver injury derived from extrahepatic mechanical
      obstruction or intrahepatic cholestasis (many causes) can induce membrane damage
      subsequent to accumulation of membranocytolytic bile acids, copper retention, and
      membrane peroxidation. This paper reviews contemporary issues of chronic
      hepatocellular injury and hepatic fibrosis with the aim of broadening the
      clinical perspective of treatment strategies.

PMID- 10200921
TI  - Determination of the prevalence of feline blood types in the UK.
AB  - The efficacy and diagnostic accuracy of a new desk-top feline blood typing kit
      was evaluated by comparing the results of the kit with traditional blood typing
      methods on 35 feline blood samples. The kit was then used to blood type 139 non
      pedigree cats from Scotland and the north of England and 207 pedigree cats from
      throughout the UK. Of the non-pedigree cats, 87.1 per cent were type A, 7.9 per
      cent were type B and 5.0 per cent were type AB, while of the pedigree cats, 54.6
      per cent were type A, 40.1 per cent were type B and 5.3 per cent were type AB.
      The majority (121 out of 207) of these pedigree cats were British shorthaired, of
      which 39.7 per cent were type A, 58.7 per cent were type B and 1.6 per cent were
      type AB. No cats were identified that failed to express the type A and/or type B
      antigens. The prevalence of type AB cats appears to be higher in this study than
      previously reported. The prevalence of blood types within specific pedigree
      breeds in the UK appears to vary from that reported elsewhere.

PMID- 10200922
TI  - Ultrasonographic estimation of prostate size in normal dogs and relationship to
      bodyweight and age.
AB  - A study was undertaken to establish the ranges of prostate dimensions, weight and
      volume in mature normal dogs and thus provide information which would allow
      differentiation from normality of size changes associated with disease. The study
      was performed on 154 healthy adult male entire dogs. Each prostate was imaged
      ultrasonographically and standard longitudinal and transverse sections were
      obtained. Prostate length (L), depth on longitudinal (DL) and transverse sections
      (DT) and width (W) were measured. Prostatic volume and weight were estimated
      according to formulae derived previously. There were statistically significant
      correlations between bodyweight or age and L, DL, DT and W. There were also
      significant correlations between estimated prostatic weight or volume and
      bodyweight, age, L, DL, DT and W. Formulae were derived to express the
      relationships between prostate size (weight or volume) and age or bodyweight.

PMID- 10200923
TI  - Discospondylitis in association with an intra-abdominal abscess in a dog.
AB  - An 11-year-old German shepherd dog cross was presented with a six-week history of
      weight loss and abdominal distension. A diagnosis of abdominal abscess and
      discospondylitis was made. The dog responded to surgical excision of the abscess
      and conservative medical treatment for discospondylitis.

PMID- 10200924
TI  - Primary immune-mediated thrombocytopenia in a cat.
AB  - A young female Somali cat was referred for investigation of chronic intermittent
      haematuria. Petechiae were found on the ears and ventral abdomen and further
      investigation revealed severe thrombocytopenia and megakaryocyte hyperplasia.
      Direct marrow immunohistochemistry detected anti-megakaryocyte autoantibody
      (Immunoglobulin G), but extensive investigation failed to find secondary causes
      of immune-mediated thrombocytopenia, so a diagnosis of primary (autoimmune)
      immune-mediated thrombocytopenia was concluded. Thrombocytopenia persisted
      despite aggressive immunosuppressive therapy (prednisolone, azathioprine and
      vincristine) but resolved after oral prednisolone was replaced with
      dexamethasone.

PMID- 10200925
TI  - Renal haemangioma in a dog.
AB  - A three-and-a-half-year-old, spayed female, crossbred dog was presented with
      chronic haematuria. Diagnostic tests included abdominal ultrasonography,
      intravenous urography, cystoscopy and nephrectomy. Renal haemangioma was
      identified as the cause of the haematuria, which resolved postoperatively. A
      subcutaneous mass developed one month after the nephrectomy, which was diagnosed
      by biopsy as a cutaneous cavernous haemangioma. No other masses were reported one
      year later.

PMID- 10200926
TI  - Intestinal volvulus in dogs: a study of four clinical cases.
AB  - Four cases of intestinal volvulus in German shepherd dogs are described. A
      definitive diagnosis was achieved by exploratory laparotomy in three cases and
      after necropsy in the remaining animal. Clinical signs, laboratory investigations
      and radiological changes are reported for three of the dogs. These dogs were all
      euthanased. Treatment of complete intestinal volvulus is difficult. By the time
      the condition is diagnosed, the pathological changes are irreversible, with
      consequent poor prognosis.

PMID- 10200927
TI  - Tuberculosis.

PMID- 10200928
TI  - Histopathological pattern and humoral immune response to a crude exo-antigen and
      purified keratinase of Microsporum canis in symptomatic and asymptomatic infected
      cats.
AB  - In order to understand better the mechanisms involved in the diverse clinical
      patterns in Microsporum canis-infected cats, the histopathological features were
      compared in symptomatic and asymptomatic infected cats. Additionally, the IgG
      immune response to a crude exo-antigen and purified keratinase of M. canis was
      studied by ELISA in cats of various clinical and mycological status. Acute and
      subacute perifolliculitis and folliculitis occurred more frequently in
      symptomatic than asymptomatic cats. The latter usually displayed signs of chronic
      inflammation and a marked infiltration of superficial dermis by mast cells, which
      would suggest that these animals present similarities to chronically
      dermatophytic humans or animals. When using a crude M. canis antigen, all
      infected cats were shown to have significantly higher levels of specific IgG when
      compared to culture negative and mechanical carrier-cats. In these non-infected
      animals, specific IgG was more frequently detected in adults than in young
      animals. No difference in anti-crude antigen specific IgG was observed between
      symptomatic and asymptomatic infected cats, indicating that the presence of IgG
      is probably unrelated to the clinical status of cats. Anti-keratinase specific
      IgG was only detected in one of the infected cats.

PMID- 10200929
TI  - Comparison of four commercialized biochemical systems for clinical yeast
      identification by colour-producing reactions.
AB  - We compared the ability of four commercially available yeast identification
      systems for routine laboratory hospital use: Auxacolor (AUX) (Sanofi Diagnostics
      Pasteur, Marne-la-Coquette), Fungichrom I (FUC) and Fungifast I Twin (FUF)
      (International Microbio, Toulon), Api Candida (API) (bioMerieux, Lyon). These
      systems are based on obtaining a biochemical profile easily defined by
      colorimetric reactions. We tested 202 yeasts belonging to 19 species which were
      included or were not included in the manufacturer's data base of the
      identification systems. Without extra tests, for all the organisms tested, after
      24 h of incubation, the percentage of organisms correctly identified was 48% for
      AUX, 75% for FUC, 77% for FUF and 81% for API. However, if we consider the ratio
      of the number of correct identifications without extra tests with the number of
      yeasts included in the manufacturers' data bases (sensitivity) the results
      increased to 61% for AUX, 81% for FUC, 91% for FUF and 83% for API. These systems
      are particularly well adapted to medical use, they are simple to set up,
      interpret, and have very good efficiency for the yeasts most commonly isolated in
      clinical specimens. The findings reported here indicate that the most favourable
      results were obtained with FUF and API systems.

PMID- 10200930
TI  - Fungistatic and fungicidal activities of murine polymorphonuclear leucocytes
      against yeast cells of Paracoccidioides brasiliensis.
AB  - Recently, a novel culture medium for detecting live yeast cells of
      Paracoccidioides brasiliensis was developed by Kurita et al. Using this culture
      medium, murine peritoneal polymorphonuclear leucocytes (PMN) were examined for
      fungistatic and fungicidal activities against P. brasiliensis yeast cells. The
      magnitude of the antifungal effect of PMN varied depending upon the fungal
      isolates used. PMN exhibited a killing effect on P. brasiliensis isolate Bt-4 in
      2 h of coculture. In contrast, the other three fungal isolates employed were
      resistant to killing by PMN. However, PMN considerably suppressed the growth of
      isolates Tatu and Recife in a long-term assay (approximately 72 h). The growth of
      isolate Bt-9 was also suppressed by PMN during the first 24 h, but was found to
      be considerably promoted at 72 h of coculture. Interferon-gamma (IFN-gamma), but
      not tumour-necrosis factor-alpha, significantly augmented the antifungal activity
      of PMN. IFN-gamma-treated PMN exhibited a killing effect on isolates Tatu, Recife
      and Bt-9 after 24 h of coculture, and showed an enhanced killing effect on
      isolate Bt-4. Contact between PMN and fungal cells was required for PMN to exert
      the antifungal effect. Our results suggest that PMN, whether activated with
      cytokines or not, might play a critical role in host resistance in early
      infection with this fungus by buying time for development of more effective
      immunologic responses.

PMID- 10200931
TI  - Molecular reidentification of human pathogenic Trichoderma isolates as
      Trichoderma longibrachiatum and Trichoderma citrinoviride.
AB  - Several species of the well-known saprophytic genus Trichoderma have been
      identified as the cause of infections in immunosuppressed humans. Because the
      differentiation and identification of Trichoderma species based on morphological
      characters only, is very difficult, two molecular approaches were applied for
      species identification. Six human pathogenic Trichoderma isolates were
      investigated by PCR-fingerprinting and analysis of ribosomal DNA internal
      transcribed spacer (ITS) sequences and compared with the corresponding data sets
      established for described species of the genus. Five of these strains were
      identified as T. longibrachiatum, whereas one single strain turned out to be T.
      citrinoviride. Both species are very closely related and belong to Trichoderma
      section Longibrachiatum. These data indicate that the occurrence of pathogenic
      Trichoderma strains may be restricted to species of section Longibrachiatum.

PMID- 10200932
TI  - In vitro susceptibility of Candida species to lactoferrin.
AB  - Lactoferrin is an antimicrobial protein present in human mucosal secretions as
      well as saliva. As there is no information on the relative fungicidal activity of
      human and bovine lactoferrin, an oral isolate of Candida albicans was studied for
      its susceptibility to these two proteins. Exposure to a concentration of 20
      micrograms ml-1 of either HLF or BLF at 37 degrees C inactivated the yeast to the
      same degree irrespective of the incubation time of 45, 90 or 150 min. A similar
      study, using 20 micrograms ml-1 BLF and an incubation time of 150 min, elicited
      varying anticandidal activity against 35 isolates belonging to six different
      Candida species. Thus, BLF was fungicidal for the six Candida species in the
      following decreasing order, C. tropicalis > C. krusei > C. albicans > C.
      guilliermondii > C. parapsilosis > C. glabrata; the latter being the most
      resistant. These Candida species also demonstrated significant intra-species
      variation in susceptibility to the protein (P < 0.05). When the yeast cells
      exposed to BLF were examined by cryo-scanning electron microscopy, profound cell
      wall changes such as cell surface blebs, swelling and cell collapse were noted.
      These findings suggest that lactoferrin, a constituent of saliva, may
      differentially modulate the carriage of Candida species in the oral cavity.

PMID- 10200934
TI  - Exophiala (Wangiella) dermatitidis keratitis after keratoplasty.
AB  - We report the first French case of an intraocular infection due to Exophiala
      (Wangiella) dermatitidis. Two months after a second corneal transplant for
      congenital hereditary endothelial dystrophy, the patient presented with ocular
      pain and corneal infiltrates leading to the graft rejection. Diagnosis was
      established by positive direct examination and cultures of the same fungus from
      corneal buttons, iris biopsies and ablated sutures.

PMID- 10200933
TI  - Serum antibody response to Cryptococcus neoformans in cats, dogs and koalas with
      and without active infection.
AB  - Anti-cryptococcal antibodies were measured in normal cats, dogs, horses and
      koalas, and cats, dogs and koalas with cryptococcosis using an enzyme
      immunoassay. Antibody levels were expressed as absorbance readings. Over 80% of
      cats and dogs with cryptococcal infection had elevated antibody levels at the
      time of diagnosis, during or after successful therapy. Antibody levels in these
      patients either remained elevated or declined slowly after treatment. For cats,
      anti-cryptococcal antibody levels were higher in C. neoformans var. gattii than
      var. neoformans infections, and lower in mild than in moderate or severe
      infections. The persistence of increased anti-cryptococcal antibody levels in
      over half of the feline and canine cases following active infection suggested the
      use of antibody determinations as a seroepidemiologic marker of previous
      infection. Consequently, antibody measurements from 'normal' animals indicated a
      prevalence of previous cryptococcal infection of 10% in cats and dogs, compared
      with 3% in horses and 5% in koalas. Preliminary studies of young animals
      suggested that anti-cryptococcal antibody levels were substantially lower in the
      young cats but not the young dogs surveyed, compared with their mature
      counterparts. The cut-offs used in the present work may thus be erroneously high,
      with a corresponding underestimation of the prevalence of inapparent
      cryptococcosis.

PMID- 10200935
TI  - Paecilomyces lilacinus fungemia in an adult bone marrow transplant recipient.
AB  - Paecilomyces lilacinus is a rare fungal pathogen in humans. We report a case of
      fungemia caused by P. lilacinus in a non-neutropenic adult, 120 days after bone
      marrow transplant. The patient's primary risk factor was the presence of an
      indwelling vascular catheter. Her initial clinical course was characterized by
      fever, chills, and rigors. Blood cultures from the central line and peripheral
      veins were positive, as was a peripheral specimen drawn after removal of the
      catheter. Two initial peripheral specimens were positive for P. lilacinus only by
      blind subculture and/or sustained incubation. She developed peripheral pulmonary
      nodules following the fungemia, thus raising the possibility of disseminated
      disease, but definitive diagnosis was confounded by Pseudomonas bacteremia. The
      nodules cleared and she recovered following removal of the central line and
      treatment with amphotericin B and 5-fluorocytosine, despite in vitro resistance
      to these antifungal drugs. This case underscores the increasing importance of P.
      lilacinus as a human pathogen capable of producing disease in immunocompetent, as
      well as in immunocompromised hosts. Also of note is that blood culture systems
      may require extended incubation or subcultures in order to detect fungi.

PMID- 10200936
TI  - Molecular cloning of a second phospholipase B gene, caPLB2 from Candida albicans.
AB  - Accumulating evidence suggests that phospholipase B, secreted by pathogenic fungi
      such as Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus,
      functions as one of the virulence factors. In the present study, we have
      attempted to clone phospholipase B gene from C. albicans. By RT-PCR analysis with
      degenerate primers based on conserved regions of phospholipase B from
      Saccharomyces cerevisiae, Penicillium notatum and Torulaspora delbrueckii two
      similar but different cDNA fragments were obtained. One corresponded to the
      partial sequence of caPLB1, recently cloned phospholipase B gene from C. albicans
      by a different approach (Leidich et al.: J Biol Chem 1998; 273: 26078-86). The
      other fragments contained sequences similar to the corresponding sequences of
      phospholipase B from other fungi. The presence of two related genes was confirmed
      by Southern and Northern blot analyses. The full length of the second C. albicans
      phospholipase B gene (caPLB2) encoded a putative protein with 608 amino acids and
      contained a potential signal peptide sequence and a putative catalytic region,
      which are found in phospholipase B from other fungi. Consistent with the findings
      of caPLB1, caPLB2 also lacks a cluster of hydrophobic amino acids at the COOH
      terminal, which may function as a signal of glycosylphosphatidylinositol anchor.

PMID- 10200937
TI  - Rapid extraction of fungal DNA from clinical samples for PCR amplification.
AB  - A hexadecyltrimethylammonium bromide (CTAB) method for isolating fungal DNA from
      clinical samples, suitable for PCR amplification is described. Yeast and
      filamentous fungi DNA from clinical samples was amplified with primers
      complementary to the genes coding for rRNA, amplifying a 105 bp fragment and
      internal transcribed spacer primers amplifying fragments between 242 and 622 bp.
      The level of sensitivity was 10 +/- 5 yeast and 28 Aspergillus fumigatus CFU ml-1
      of biological fluid.

PMID- 10200938
TI  - Study of diseases of the grey squirrel (Sciurus carolinensis) in Italy. First
      isolation of the dermatophyte Microsporum cookei.
AB  - The ecological risks connected with the introduction of the North American grey
      squirrel (Sciurus carolinensis) in Italy are many. Of particular importance is
      the conservation of the native red squirrel (S. vulgaris) population, since the
      experience from the British Isles showed that where the grey squirrel was
      introduced, the autochthonous red squirrel became extinct. To determine the
      health status of grey squirrels trapped and euthanasized during an eradication
      campaign in the Piedmont region, various analyses were carried out. This paper
      describes a preliminary mycological investigation. Microsporum cookei, a
      geophilic dermatophyte, was isolated for the first time from grey squirrels.

PMID- 10200939
TI  - Comment on the correspondence between Dr J. Guarro and Dr C. Rajendran in Medical
      Mycology 1998; 36: 349-50.

PMID- 10200940
TI  - Human embryonic stem cells: the future of transplantation medicine?

PMID- 10200941
TI  - Targeting protein breakdown to treat cancer.

PMID- 10200942
TI  - Virus buster for transfusion blood.

PMID- 10200943
TI  - Turning off RB for a healthy heart?

PMID- 10200944
TI  - Sepsis and mediator-directed therapy: rethinking the target populations. Mediator
      directed therapy in sepsis: rethinking the target populations. Toronto, Canada,
      31 October-1 November 1998.

PMID- 10200945
TI  - Peroxidases and human disease: a meeting of minds. The peroxidase multigene
      family of enzymes: biochemical basis and clinical applications. Fraueninsel,
      Germany, 27 September-2 October 1998.

PMID- 10200946
TI  - Is extravasation a Fas-regulated process?
AB  - The monolayer of endothelial cells that coats the luminal surface of the vessel
      wall has numerous physiological functions, including the prevention of
      coagulation, control of vascular permeability, maintenance of vascular tone and
      regulation of leukocyte extravasation. Recently, we detected functional Fas
      ligand (FasL) expression on the endothelial lining of blood vessels. FasL induces
      apoptotic cell death in the multitude of cell types that express its receptor,
      Fas. Here, we review the function of vascular endothelium in controlling
      leukocyte extravasation, and illustrate how the regulation of endothelial FasL
      expression might contribute to this process. We also describe the role of
      leukocyte extravasation in angiogenesis and atherosclerosis, and we suggest that
      FasL gene transfer might provide a means of treating diseases of the
      proliferative vessel wall, particularly those that result from the detrimental
      infiltration of inflammatory cells.

PMID- 10200947
TI  - Urinary analyte screening: a noninvasive detection method for Down syndrome?
AB  - Prenatal screening for Down syndrome using maternal serum markers achieves
      detection rates of 60-80% with a 5% false positive rate. Improvement in the
      accuracy of screening, as well as its ease and safety, will increase the use of
      such tests. The most effective of the current serum markers is human chorionic
      gonadotropin (hCG). Studies on beta core fragment (beta CF), the major urinary
      metabolite of hCG, have indicated that screening with beta CF and other markers
      measured in maternal urine might improve the detection of Down syndrome and
      provide a less expensive and simpler test. However, recent results have been
      unusually variable. Although it has great potential, the true clinical value of
      maternal urine screening to detect Down syndrome still remains to be determined.

PMID- 10200948
TI  - New perspectives on the etiology of systemic sclerosis.
AB  - Systemic sclerosis (SSc) is a disease of unknown origin. Although SSc is
      considered to be an autoimmune disease, recent studies have implicated cellular
      microchimerism in its pathogenesis. Microchimerism results from the persistence
      of fetal cells, from prior pregnancies, in the maternal circulation. The
      demonstration of the presence of fetal CD3+ T cells in the maternal circulation
      and of fetal cells in affected SSc tissues suggests that microchimerism might
      cause SSc in certain patients by initiating a graft-versus-host-like response.

PMID- 10200949
TI  - Neuropeptide Y: a key molecule in anorexia and cachexia in wasting disorders?
AB  - Anorexia and body weight loss are characteristic of many diseases, including
      cancer and AIDS. Recent studies indicate that inflammatory cytokines, such as
      interleukin 1, the interleukin 6 subfamily and tumor necrosis factor, induce
      anorexia and cachexia by inhibiting the normal adaptive feeding response to
      energy deficits. Here, I discuss the evidence for and against a central role for
      neuropeptide Y and leptin in anorexia and cachexia.

PMID- 10200950
TI  - Xeroderma pigmentosum and the role of UV-induced DNA damage in skin cancer.
AB  - Xeroderma pigmentosum (XP) is a rare, autosomal recessive disease that is
      characterized by the extreme sensitivity of the skin to sunlight. Compared to
      normal individuals, XP patients have a more than 1000-fold increased risk of
      developing cancer on sun-exposed areas of the skin. Genetic and molecular
      analyses have revealed that the repair of ultraviolet (UV)-induced DNA damage is
      impaired in XP patients owing to mutations in genes that form part of a DNA
      repair pathway known as nucleotide excision repair (NER). Two other diseases,
      Cockayne syndrome (CS) and the photosensitive form of trichothiodystrophy (TTD),
      are linked to a defect in the NER pathway. Strikingly, although CS and TTD
      patients are UV-sensitive, they do not develop skin cancer. The recently
      developed animal models that mimic the human phenotypes of XP, CS and TTD will
      contribute to a better understanding of the etiology of these diseases and the
      role of UV-induced DNA damage in the development of skin cancer.

PMID- 10200951
TI  - Control of sigma factor activity during Bacillus subtilis sporulation.
AB  - When starved, Bacillus subtilis undergoes asymmetric division to produce two cell
      types with different fates. The larger mother cell engulfs the smaller forespore,
      then nurtures it and, eventually, lyses to release a dormant, environmentally
      resistant spore. Driving these changes is a programme of transcriptional gene
      regulation. At the heart of the programme are sigma factors, which become active
      at different times, some only in one cell type or the other, and each directing
      RNA polymerase to transcribe a different set of genes. The activity of each sigma
      factor in the cascade is carefully regulated by multiple mechanisms. In some
      cases, novel proteins control both sigma factor activity and morphogenesis, co
      ordinating the programme of gene expression with morphological change. These
      bifunctional proteins, as well as other proteins involved in sigma factor
      activation, and even precursors of sigma factors themselves, are targeted to
      critical locations, allowing the mother cell and forespore to communicate with
      each other and to co-ordinate their programmes of gene expression. This
      signalling can result in proteolytic sigma factor activation. Other mechanisms,
      such as an anti-sigma factor and, perhaps, proteolytic degradation, prevent sigma
      factors from becoming active in the wrong cell type. Accessory transcription
      factors modulate RNA polymerase activity at specific promoters. Negative feedback
      loops limit sigma factor production and facilitate the transition from one sigma
      factor to the next. Together, the mechanisms controlling sigma factor activity
      ensure that genes are expressed at the proper time and level in each cell type.

PMID- 10200952
TI  - Transcription initiation in Archaea: facts, factors and future aspects.
AB  - The basal apparatus for transcription initiation in Archaea is more closely
      related to the eukaryal than to the bacterial counterpart. The understanding of
      archaeal transcription initiation has been deepened by recent advances, which
      include genome sequencing, biochemical approaches and the structure determination
      of a protein DNA complex. Archaeal promoter elements, transcription factors, RNA
      polymerase and their interactions are discussed and compared with the eukaryal
      situation. It is emerging that transcription initiation is not uniform in
      Archaea. A minimal set of promoter elements and transcription factors is
      conserved, but the relative importance for transcription initiation can vary.
      Furthermore, additional basal transcription factors and promoter elements seem to
      be crucial in subgroups of Archaea. Finally, some aspects of global as well as
      gene-specific transcriptional regulation are discussed.

PMID- 10200953
TI  - Structure, assembly and regulation of expression of capsules in Escherichia coli.
AB  - Many Escherichia coli strains are covered in a layer of surface-associated
      polysaccharide called the capsule. Capsular polysaccharides represent a major
      surface antigen, the K antigen, and more than 80 distinct K serotypes result from
      structural diversity in these polymers. However, not all capsules consist of K
      antigen. Some are due to production of an extensive layer of a polymer
      structurally identical to a lipopolysaccharide O antigen, but distinguished from
      lipopolysaccharide by the absence of terminal lipid A-core. Recent research has
      provided insight into the manner in which capsules are organized on the Gram
      negative cell surface, the pathways used for their assembly, and the regulatory
      processes used to control their expression. A limited repertoire of capsule
      expression systems are available, despite the fact that the producing bacteria
      occupy a variety of ecological niches and possess diverse physiologies. All of
      the known capsule assembly systems seen in Gram-negative bacteria are represented
      in E. coli, as are the majority of the regulatory strategies. Escherichia coli
      therefore provides a variety of working models on which studies in other bacteria
      are (or can be) based. In this review, we present an overview of the current
      molecular and biochemical models for capsule expression in E. coli. By taking
      into account the organization of capsule gene clusters, details of the assembly
      pathway, and regulatory features that dictate capsule expression, we provide a
      new classification system that separates the known capsules of E. coli into four
      distinct groups.

PMID- 10200954
TI  - Gene products required for surface expression of the capsular form of the group 1
      K antigen in Escherichia coli (O9a:K30).
AB  - The group 1 K30 antigen from Escherichia coli (O9a:K30) is present on the cell
      surface as both a capsular structure composed of high-molecular-weight K30
      polysaccharide and as short K30 oligosaccharides linked to lipid A-core in a
      lipopolysaccharide molecule (K30LPS). To determine the molecular processes that
      are responsible for the two forms of K antigen, the 16 kb chromosomal cps region
      has been characterized. This region encodes 12 gene products required for the
      synthesis, polymerization and translocation of the K30 antigen. The gene products
      include four glycosyltransferases responsible for synthesis of the K30 repeat
      unit; a PST (1) exporter (Wzx), required to transfer lipid-linked K30 units
      across the plasma membrane to the periplasmic space; and a K30-antigen polymerase
      (Wzy). These gene products are typical of those seen in O-antigen biosynthesis
      gene clusters and they interact with the lipopolysaccharide translocation pathway
      to express K30LPS on the cell surface. The same gene products also provide the
      biosynthetic intermediates for the capsule assembly pathway, although they are
      not in themselves sufficient for synthesis of the K30 capsule. Three additional
      genes, wza, wzb and wzc, encode homologues to proteins that are encoded by gene
      clusters involved in expression of a variety of bacterial exopolysaccharides.
      Mutant analysis indicates that Wza and Wzc are required for wild-type surface
      expression of the capsular structure but are not essential for polymerization and
      play no role in the translocation of K30LPS. These surface expression components
      provide the key feature that distinguishes the assembly systems for O antigens
      and capsules.

PMID- 10200955
TI  - Secretion of ATP-utilizing enzymes, nucleoside diphosphate kinase and ATPase, by
      Mycobacterium bovis BCG: sequestration of ATP from macrophage P2Z receptors?
AB  - Mycobacterium bovis BCG secretes two ATP-scavenging enzymes, nucleoside
      diphosphate kinase (Ndk) and ATPase, during growth in Middlebrook 7H9 medium. In
      synthetic Sauton medium without any protein supplements, there is less secretion
      of these two enzymes unless proteins such as bovine serum albumin (BSA),
      ovalbumin or extracts of macrophages are added to the medium. There is a gradient
      of activity among various proteins in triggering the induction of secretion of
      these two enzymes. Other mycobacteria, such as M. smegmatis, primarily secrete
      Ndk, while M. chelonae does not appear to secrete either of these two enzymes.
      Purification of the enzymes from the culture filtrate of 7H9-grown M. bovis BCG
      cells and determination of the N-terminal amino-acid sequence have demonstrated a
      high level of sequence identity of one of the ATPases with DnaK, a heat shock
      chaperone, of M. tuberculosis and M. leprae, while that of Ndk shows significant
      identity with the Ndk of Myxococcus xanthus. As both Ndk and ATPase use ATP as a
      substrate, the physiological significance of the secretion of these two ATP
      utilizing enzymes was explored. External ATP is important in the activation of
      macrophage surface-associated P2Z receptors, whose activation has been postulated
      to allow phagosome-lysosome fusion and macrophage cell death. We demonstrate that
      the presence of the filtrate containing these enzymes prevents ATP-induced
      macrophage cell death, as measured by the release of an intracellular enzyme,
      lactate dehydrogenase. In vitro complexation studies with purified Ndk/ATPase and
      hyperproduced P2Z receptor protein will demonstrate whether these enzymes may be
      used by mycobacteria to sequester ATP from the macrophage P2Z receptors, thereby
      preventing phagosome-lysosome fusion or macrophage apoptotic death.

PMID- 10200956
TI  - The comP locus of Neisseria gonorrhoeae encodes a type IV prepilin that is
      dispensable for pilus biogenesis but essential for natural transformation.
AB  - The expression of type IV pili (Tfp) by Neisseria gonorrhoeae has been shown to
      be essential for natural genetic transformation at the level of sequence-specific
      uptake of DNA. All previously characterized mutants defective in this step of
      transformation either lack Tfp or are altered in the expression of Tfp-associated
      properties, such as twitching motility, autoagglutination and the ability to bind
      to human epithelial cells. To examine the basis for this relationship, we
      identified potential genes encoding polypeptides sharing structural similarities
      to PilE, the Tfp subunit, within the N. gonorrhoeae genome sequence database. We
      found that disruption of one such gene, designated comP (for competence
      associated prepilin), leads to a severe defect in the capacity to take up DNA in
      a sequence-specific manner, but does not alter Tfp biogenesis or expression of
      the Tfp-associated properties of auto-agglutination, twitching motility and human
      epithelial cell adherence. Indirect evidence based on immunodetection suggests
      that ComP is expressed at very low levels relative to that of PilE. The process
      of DNA uptake in gonococci, therefore, is now known to require the expression of
      at least three distinct components: Tfp, the recently identified PilT protein and
      ComP.

PMID- 10200957
TI  - Essential role of Helicobacter pylori gamma-glutamyltranspeptidase for the
      colonization of the gastric mucosa of mice.
AB  - Constitutive expression of gamma-glutamyltranspeptidase (GGT) activity is common
      to all Helicobacter pylori strains, and is used as a marker for identifying H.
      pylori isolates. Helicobacter pylori GGT was purified from sonicated extracts of
      H. pylori strain 85P by anion exchange chromatography. The N-terminal amino acid
      sequences of two of the generated endo-proteolysed peptides were determined,
      allowing the cloning and sequencing of the corresponding gene from a genomic H.
      pylori library. The H. pylori ggt gene consists of a 1681 basepair (bp) open
      reading frame encoding a protein with a signal sequence and a calculated
      molecular mass of 61 kDa. Escherichia coli clones harbouring the H. pylori ggt
      gene exhibited GGT activity at 37 degrees C, in contrast to E. coli host cells
      (MC1061, HB101), which were GGT negative at 37 degrees C. GGT activity was found
      to be constitutively expressed by similar genes in Helicobacter felis,
      Helicobacter canis, Helicobacter bilis, Helicobacter hepaticus and Helicobacter
      mustelae. Western immunoblots using rabbit antibodies raised against a His-tagged
      GGT recombinant protein demonstrated that H. pylori GGT is synthesized in both H.
      pylori and E. coli as a pro-GGT that is processed into a large and a small
      subunit. Deletion of a 700 bp fragment within the GGT-encoding gene of a mouse
      adapted H. pylori strain (SS1) resulted in mutants that were GGT negative yet
      grew normally in vitro. These mutants, however, were unable to colonize the
      gastric mucosa of mice when orally administered alone or together (co-infection)
      with the parental strain. These results demonstrate that H. pylori GGT activity
      has an essential role for the establishment of the infection in the mouse model,
      demonstrating for the first time a physiological role for a bacterial GGT enzyme.

PMID- 10200958
TI  - Specific expression of the Fusarium transposon Fot1 and effects on target gene
      transcription.
AB  - The Fot1 transposon is active in some strains of the plant pathogenic fungus
      Fusarium oxysporum. In a high-copy-number strain that contains autonomous
      elements, we have detected a transcript of 1.7 kb hybridizing to Fot1 in very low
      amounts. Mapping the 3' and 5' termini of this transcript confirms that it
      corresponds to a Fot1-specific transcript. In this strain, five independent
      mutants of the transgene (niaD) encoding nitrate reductase have arisen by
      insertion of Fot1 into the third intron. The analysis of the effect of Fot1
      insertion in these mutants shows that, depending on the orientation of Fot1
      relative to niaD, different truncated chimeric niaD-Fot1 transcripts are
      produced. Mapping the 5' and 3' ends of these transcripts reveals (i) premature
      polyadenylation at sites present in the 5' and 3' untranslated regions of Fot1,
      and (ii) initiation of some transcripts in the 3' part of the niaD gene at sites
      located immediately downstream of the Fot1 insertion. Thus, a novel promoter,
      associated with the end of Fot1, directs transcriptional activity outwards from
      the element into the coding sequence of the niaD gene. These effects demonstrate
      that Fot1 insertion provides an additional general mechanism controlling fungal
      gene expression.

PMID- 10200959
TI  - A deletion within the translocation domain of Pseudomonas exotoxin A enhances
      translocation efficiency and cytotoxicity concomitantly.
AB  - Pseudomonas exotoxin A (PE) is a cytotoxin composed of three structural domains.
      Domain I is responsible for cell binding, domain II for membrane translocation
      enabling access to the cytosol, and domain III for the catalytic inactivation of
      protein synthesis, which results in cell death. To investigate the role of the
      six alpha-helices (A-F) that form the translocation domain, we deleted them
      successively one at a time. All mutants showed native cell-binding and catalytic
      activities, indicating that deletions specifically affected translocation
      activity. This step of the intoxication procedure was examined directly using a
      cell-free translocation assay, and indirectly by monitoring cytotoxicity.
      Translocation activity and log(cytotoxicity) were highly correlated, directly
      indicating that translocation is rate limiting for PE intoxication. Deletion of
      B, C and D helices resulted in non-toxic and non-translocating molecules, whereas
      mutants lacking the A or E helix displayed significant cytotoxicity albeit 500
      fold lower than native PE. We concluded that B, C and D helices, which make up
      the core of domain II, are essential, whereas the more peripheral A and E helices
      are comparatively dispensable. The last helix (F) is inhibitory for translocation
      because its deletion produced a mutant displaying a translocation activity 60%
      higher than PE, along with a three- to sixfold increase in cytotoxicity in all
      tested cell lines. This toxin is the most in vitro active PE mutant obtained
      until now. Finally, partial duplication of domain II did not give rise to a more
      actively translocated PE, but rather to a threefold less active molecule.

PMID- 10200960
TI  - Sequence-specific cleavage by bacteriophage T4 endonuclease II in vitro.
AB  - The 136 codon (408 bp) denA gene encoding endonuclease II (Endoll) of
      bacteriophage T4 was unambiguously identified through sequencing and subsequent
      cloning. Endoll prepared from cloned DNA through coupled in vitro transcription
      translation nicked and cut DNA in vitro in a sequence-specific manner. In vitro
      (and in vivo), the bottom strand was nicked between the first and second base
      pair to the right of a top-strand CCGC motif shared by favoured in vitro and in
      vivo cleavage sites; top-strand cleavage positions varied. To the right of the
      cleavage position, favoured in vitro sites lacked a sequence element conserved at
      favoured in vivo sites. In pBR322 DNA, the sites cleaved in vivo as previously
      described were also cleaved in vitro, but in vitro additional sites were nicked
      or cleaved and the preference for individual sites was different. Also, different
      from the in vivo reaction, nicking was more frequent than ds cutting; in many
      copies of a ds cleavage site, only the bottom strand was nicked in vitro. A model
      is discussed in which sequential nicking of the two strands, and different
      factors influencing bottom-strand nicking and top-strand nicking, can explain the
      differences between the in vitro and the in vivo reaction.

PMID- 10200961
TI  - The SpoIIE phosphatase, the sporulation septum and the establishment of forespore
      specific transcription in Bacillus subtilis: a reassessment.
AB  - Making a spore in Bacillus subtilis requires the formation of two cells, the
      forespore and the mother cell, which follow dissimilar patterns of gene
      expression. Cell specificity is first established in the forespore under the
      control of the sigma F factor, which is itself activated through the action of
      the SpoIIE serine phosphatase, an enzyme targeted to the septum between the two
      cells. Deletion of the 10 transmembrane segments of the SpoIIE protein leads to
      random distribution of SpoIIE in the cytoplasm. Activation of sigma F is slightly
      delayed and less efficient than in wild type, but it remains restricted to the
      forespore in a large proportion of cells and the bacteria sporulate with 30%
      efficiency. Overexpression of the complete SpoIIE protein in a divIC mutant leads
      to significant sigma F activity, indicating that the septum requirement for
      activating sigma F can be bypassed. In contradiction to current models, we
      propose that genetic asymmetry is not created by unequal distribution of SpoIIE
      within the sporangium, but by exclusion of an inhibitor of SpoIIE from the
      forespore. This putative inhibitor would be a cytoplasmic molecule that interacts
      with SpoIIE and shuts off its phosphatase activity until it disappears
      specifically from the forespore.

PMID- 10200962
TI  - Identification of UreR binding sites in the Enterobacteriaceae plasmid-encoded
      and Proteus mirabilis urease gene operons.
AB  - The closely related Proteus mirabilis and Enterobacterlaceae plasmid-encoded
      urease genes are positively regulated by the AraC-like transcriptional activator
      UreR. In the presence of the effector molecule urea, UreR promotes transcription
      of ureD, the initial gene in the urease operon, and increases transcription of
      the divergently transcribed ureR. Here, we identify UreR-specific binding sites
      in the ureRp-ureDp intergenic regions. Recombinant UreR (rUreR) was expressed and
      purified, and gel shift and DNase I protection assays were performed with this
      protein. These analyses indicated that there are two distinct rUreR binding sites
      in both the plasmid-encoded and P. mirabilis ureRp-ureDp intergenic regions. A
      consensus binding site of TA/GT/CA/TT/GC/TTA/TT/AATTG was predicted from the
      DNase I protection assays. Although rUreR bound to the specific DNA binding site
      in both the presence and the absence of urea, the dissociation rate constant k-1
      of the rUreR-DNA complex interaction was measurably different when urea was
      present. In the absence of urea, the dissociation of the protein-DNA complexes,
      for both ureRp and ureDp, was complete at the earliest time point, and it was not
      possible to determine a rate. In the presence of urea, dissociation was
      measurable with a k-1 for the rUreR-ureRp interaction of 1.2 +/- 0.2 x 10(-2) s-1
      and a k-1 for the rUreR-ureDp interaction of 2.6 +/- 0.1 x 10(-3) s-1. This
      corresponds to a half-life of the ureRp-rUreR interaction of 58 s, and a half
      life of the ureDp-rUreR interaction of 4 min 26 s. A model describing a potential
      role for urea in the activation of these promoters is proposed.

PMID- 10200963
TI  - Characterization of Escherichia coli cspE, whose product negatively regulates
      transcription of cspA, the gene for the major cold shock protein.
AB  - Escherichia coli contains nine members of the CspA protein family from CspA to
      Cspl. To elucidate the cellular function of CspE, we constructed a delta cspE
      strain. CspE is highly produced at 37 degrees C. The synthesis level of CspE
      transiently increased during the growth lag period after dilution of stationary
      phase cells into the fresh medium at 37 degrees C. This is consistent with the
      delta cspE phenotype of the longer growth lag period after dilution. The protein
      synthesis patterns of the delta cspE strain and the wild-type strain were
      compared using two-dimensional gel electrophoresis. In the delta cspE strain, the
      synthesis of a number of proteins at 37 degrees C was found to be altered and
      cspA was derepressed. The derepression of cspA in the delta cspE strain was at
      the level of transcription in a promoter-independent fashion but was not caused
      by stabilization of the cspA mRNA, which was shown to be a major cause of CspA
      induction after cold shock. In vitro transcription assays demonstrated that both
      CspE and CspA enhanced transcription pause at the region immediately downstream
      of the cold box, a putative repressor binding site on the cspA mRNA. In a cell
      free protein synthesis system using S-30 cell extracts, CspA production was
      specifically inhibited by the addition of CspE. These results indicate that CspE
      functions as a negative regulator for cspA expression at 37 degrees C, probably
      by interacting with the transcription elongation complex at the cspA cold box
      region.

PMID- 10200964
TI  - The lipopolysaccharide outer core of Yersinia enterocolitica serotype O:3 is
      required for virulence and plays a role in outer membrane integrity.
AB  - Lipopolysaccharide (LPS) of Yersinia enterocolitica O:3 has an inner core linked
      to both the O-antigen and to an outer core hexasaccharide that forms a branch.
      The biological role of the outer core was studied using polar and non-polar
      mutants of the outer core biosynthetic operon. Analysis of O-antigen- and outer
      core-deficient strains suggested a critical role for the outer core in outer
      membrane properties relevant in resistance to antimicrobial peptides and
      permeability to hydrophobic agents, and indirectly relevant in resistance to
      killing by normal serum. Wild-type bacteria but not outer core mutants killed
      intragastrically infected mice, and the intravenous lethal dose was approximately
      10(4)-fold higher for outer core mutants. After intragastric infection, outer
      core mutants colonized Peyer's patches and invaded mesenteric lymph nodes, spleen
      and liver, and induced protective immunity against wild-type bacteria. In mice co
      infected intragastrically with an outer core mutant-wild type mixture, both
      strains colonized Peyer's patches similarly during the first 2 days, but the
      mutant was much less efficient in colonizing deeper organs and was cleared faster
      from Peyer's patches. The results demonstrate that outer core is required for Y.
      enterocolitica O:3 full virulence, and strongly suggest that it provides
      resistance against defence mechanisms (most probably those involving bactericidal
      peptides).

PMID- 10200965
TI  - Expression of different group A streptococcal M proteins in an isogenic
      background demonstrates diversity in adherence to and invasion of eukaryotic
      cells.
AB  - The M protein of group A streptococcus (GAS) is considered to be a major
      virulence factor because it renders GAS resistant to phagocytosis and allows
      bacterial growth in human blood. There are more than 80 known serotypes of M
      proteins, and protective opsonic antibodies produced during disease in humans are
      serotype specific. M proteins also mediate bacterial adherence to epithelial
      cells of skin and pharynx. GAS strains vary in the genomic organization of the
      mga regulon, which contains the genes encoding M and M-like proteins and other
      virulence factors. This diversity of organization makes it difficult to assess
      virulence of M proteins of different serotypes, unless they can be expressed in
      an isogenic background. Here, we express M proteins of different serotypes in the
      M protein- and protein F1-deficient GAS strain, SAM2, which also lacks M-like
      proteins. Genes encoding M proteins of different serotypes (emmXs) have been
      integrated into the SAM2 chromosome in frame with the emm6.1 promoter and its mga
      regulon, resulting in similar levels of emmX expression. Although SAM2 exhibits a
      very low level of adherence to and invasion of HEp-2 and HaCaT cells, a SAM2
      derived strain expressing M6 protein adheres to and invades both cell types. In
      contrast, the isogenic strain expressing M18 protein adheres to both cell types,
      but invades with a very low efficiency. A strain expressing M3 protein adheres to
      both types of cells, but its invasion of HEp-2 cells is serum dependent. A GAS
      strain expressing M6 protein does not compete with the isogenic strain expressing
      M18 protein for adherence to or invasion of HaCaT cells. We conclude that M
      proteins of different serotypes recognize different repertoires of receptors on
      the surfaces of eukaryotic cells.

PMID- 10200967
TI  - Induction of an AP endonuclease activity in Streptococcus mutans during growth at
      low pH.
AB  - The oral microbe Streptococcus mutans uses adaptive mechanisms to withstand the
      fluctuating pH levels in its natural environment. The regulation of protein
      synthesis is part of the mechanism of acid adaptation and tolerance in S. mutans.
      Here, we demonstrate that the organism's acid-inducible protein repertoire
      includes an AP endonuclease activity. This abasic site-specific endonuclease
      activity is present at greater levels in cells grown at low pH than in cells
      grown at pH 7, and is apparently independent of the RecA protein. Experiments
      using tetrahydrofuran or alpha-deoxyadenosine-containing substrates indicate that
      the activity induced at low pH may be similar to the activity of exonuclease III
      from E. coli. Acid-adapted S. mutans also shows an increased survival rate after
      exposure to near-UV radiation in both the wild type and a recA strain. Far-UV
      radiation resistance is observed in the wild type only. The endonuclease activity
      was purified approximately 500-fold from an S. mutans recA mutant strain grown at
      pH 5. Initial characterization revealed a 3' to 5' exonuclease activity, and
      showed additional functional similarities to DNA repair enzymes from other
      organisms.

PMID- 10200966
TI  - Pneumococcal licD2 gene is involved in phosphorylcholine metabolism.
AB  - Phosphorylcholine is an important bioactive adduct to the teichoic acid (TA) and
      lipoteichoic acid (LTA) of the surface of Streptococcus pneumoniae. We have
      identified and characterized a genetic locus lic that is required for
      phosphorylcholine metabolism in S. pneumoniae. The pneumococcal lic locus
      consists of eight genes, licA, licB, licC and licD1, licD2 and three additional
      open reading frames. Pneumococcal licA, licB, licC, licD1 and licD2 have
      significant sequence similarity to licA, licB, licC and licD of Haemophilus
      influenzae. Mutation of licD2 led to decreased [3H]-choline uptake, aberrant
      migration of LTA chains in SDS-PAGE gels, loss of several surface proteins, and a
      phase-locked hypertransparent colony phenotype. Moreover, the licD2- mutant
      falled to undergo lysis after treatment with penicillin at high cell density and
      showed decreased transformation competence. Finally, the licD2- mutant
      demonstrated decreased adherence to the human type II alveolar cells, reduced
      nasopharyngeal colonization in infant rats, as well as significantly impaired
      virulence upon intraperitoneal challenge of CF1 mice. Identification of the lic
      genes in the pneumococcus will facilitate further characterization of the role of
      surface choline in microbial physiology and pathogenesis.

PMID- 10200969
TI  - Physical and genetic map of the genome of Vibrio parahaemolyticus: presence of
      two chromosomes in Vibrio species.
AB  - We constructed a physical map of the genomic DNA (5.1 Mb) for Vibrio
      parahaemolyticus strain AQ4673 by combining 17 adjacent NotI fragments. This map
      shows two circular replicons of 3.2 and 1.9 Mb. Pulsed-field gel electrophoresis
      (PFGE) of undigested genomic DNA revealed two bands of corresponding sizes.
      Analysis both by NotI digestion and by Southern blot of the two isolated bands
      confirmed the existence of two replicons. The presence of genes for 16S rRNA on
      both the replicons indicates that the replicons are chromosomes rather than
      megaplasmids. The two bands were also seen after PFGE of undigested genomic DNA
      of V. parahaemolyticus strains other than AQ4673, and of strains belonging to
      other Vibrio species, such as V. vulnificus, V. fluvialis and various serovars
      and biovars of V. cholerae. It is noteworthy that V. cholerae O1 strain 569B, a
      classical biovar, was also shown to have two replicons of 2.9 and 1.2 Mb, which
      does not agree with a physical map proposed in a previous study. Our results
      suggest that a two-replicon structure is common throughout Vibrio species.

PMID- 10200968
TI  - Overexpression of yeast karyopherin Pse1p/Kap121p stimulates the mitochondrial
      import of hydrophobic proteins in vivo.
AB  - During evolution, cellular processes leading to the transfer of genetic
      information failed to send all the mitochondrial genes into the nuclear genome.
      Two mitochondrial genes are still exclusively located in the mitochondrial genome
      of all living organisms. They code for two highly hydrophobic proteins: the
      apocytochrome b and the subunit I of cytochrome oxidase. Assuming that the
      translocation machinery could not efficiently transport long hydrophobic
      fragments, we searched for multicopy suppressors of this physical blockage. We
      demonstrated that overexpression of Pse1p/Kap121p or Kap123p, which belong to the
      superfamily of karyopherin beta proteins, facilitates the translocation of
      chimeric proteins containing several stretches of apocytochrome b fused to a
      reporter mitochondrial gene. The effect of PSE1/KAP121 overexpression (in which
      PSE1 is protein secretion enhancer 1) on mitochondrial import of the chimera is
      correlated with an enrichment of the corresponding transcript in cytoplasmic
      ribosomes associated with mitochondria. PSE1/KAP121 overexpression also improves
      the import of the hydrophobic protein Atm1p, an ABC transporter of the
      mitochondrial inner membrane. These results suggest that in vivo PSE1/KAP121
      overexpression facilitates, either directly or indirectly, the co-translational
      import of hydrophobic proteins into mitochondria.

PMID- 10200970
TI  - Two operons that encode FNR-like proteins in Lactococcus lactis.
AB  - Global regulatory circuits of the type mediated by CRP and FNR in Escherichia
      coli were sought in Lactococcus lactis to provide a basis for redirecting carbon
      metabolism to specific fermentation products. Using a polymerase chain reaction
      (PCR) approach, two genes (flpA and flpB) encoding FNR-like proteins (FlpA and
      FlpB) with the potential for mediating a dithiol-disulphide-dependent regulatory
      switch, were identified. Transcript analysis indicated that they are distal genes
      of two paralogous operons, orfX-orfY-flp, in which the orfX and orfY genes were
      predicted to encode binding domain components of cation ATPases and storage
      proteins respectively. The corresponding promoters were each associated with a
      potential FNR site (TTGAT----ATCAA) at positions +4.5 (flpA operon) and -42.5
      (flpB operon), suggesting that the respective operons might be negatively and
      positively autoregulated. The incomplete open reading frames (orfWA/B) located
      upstream of each operon were predicted to encode additional components of
      paralogous cation ATPases. No phenotypic effects were detected in flpA and flpB
      single mutants, but the double mutant had a lower intracellular zinc content, an
      increased sensitivity to hydrogen peroxide and an altered polypeptide profile (as
      determined by two-dimensional gel electrophoresis): formate production was not
      affected. It was concluded tentatively that FlpA and FlpB regulate overlapping
      modulons, including systems concerned with zinc uptake, in response to metal ion
      or oxidative stress.

PMID- 10200971
TI  - Genetic and functional characterization of the alpAB gene locus essential for the
      adhesion of Helicobacter pylori to human gastric tissue.
AB  - In this study, we isolated and characterized a chromosomal locus of Helicobacter
      pylori previously identified by transposon shuttle mutagenesis as being involved
      in the adhesion of the pathogen to gastric epithelial cells. Two closely
      homologous genes were identified, designated as alpA and alpB, encoding outer
      membrane (OM) proteins of 518 amino acids each. They are members of the outer
      membrane protein supergene family identified in the H. pylori 26695 complete
      genome sequence. AlpA carries a functional lipoprotein signal sequence. AlpB
      carries a putative standard N-terminal signal sequence and shows a strong amino
      acid sequence identity to AlpA. Transposon insertion mutagenesis, immunoblotting
      and primer extension studies indicate that both genes are organized in an operon,
      but no obvious consensus promoter sequence was found upstream of the
      transcriptional start site. The C-terminal portion of both proteins is predicted
      to form a porin-like beta-barrel in the outer membrane, consisting of 14
      transmembrane amphipathic beta-strands. Adhesion experiments with defined
      isogenic mutants indicate that both proteins are necessary for specific adherence
      of H. pylori to human gastric tissue. The pattern of AlpAB-dependent adherence of
      H. pylori to the gastric epithelial surface shows a clear difference to the BabA2
      mediated adherence to Lewis, suggesting that a different receptor is involved.

PMID- 10200972
TI  - Mta, a global MerR-type regulator of the Bacillus subtilis multidrug-efflux
      transporters.
AB  - Little is known about the natural functions of multidrug-efflux transporters
      expressed by bacteria. Although identified as membrane proteins actively
      extruding exogenous toxins from the cell, they may actually be involved in the
      transport of as yet unidentified specific natural substrates. The expression of
      two highly similar multidrug transporters of Bacillus subtilis, Bmr and Blt, is
      regulated by specific transcriptional activators, BmrR and BltR, respectively,
      which respond to different inducer molecules, thus suggesting distinct functions
      for the two transporters. Here, we describe an alternative mechanism of
      regulation, which involves a global transcriptional activator, Mta, a member of
      the MerR family of bacterial regulatory proteins. The individually expressed N
      terminal DNA-binding domain of Mta interacts directly with the promoters of bmr
      and blt and induces transcription of these genes. Additionally, this domain
      stimulates the expression of the mta gene itself and at least one more gene,
      ydfK, which encodes a hypothetical membrane protein. These results and the
      similarity of Mta to the thiostrepton-induced protein TipA of Streptomyces
      lividans strongly suggest that Mta is an autogenously controlled global
      transcriptional regulator, whose activity is stimulated by an as yet unidentified
      inducer. This stimulation is mimicked by the removal of the C-terminal inducer
      binding domain. The fact that both Bmr and Blt are controlled by this regulator
      demonstrates that some of their functions are either identical or, at least,
      related. Further analysis of Mta-mediated regulation may reveal the natural
      function of the system of multidrug transporters in B. subtilis and serve as a
      paradigm for similar systems in other bacteria.

PMID- 10200973
TI  - Lipid domains of mycobacteria studied with fluorescent molecular probes.
AB  - The complex mycobacterial cell envelope is recognized as a critical factor in our
      failure to control tuberculosis, leprosy and other non-tuberculous pathogens.
      Although its composition has been extensively determined, many details regarding
      the organization of the envelope remain uncertain. This is particularly so for
      the non-covalently bound lipids, whose natural distribution may be disrupted by
      conventional biochemical or cytological techniques. In order to study the native
      organization of lipid domains in the mycobacterial envelope, we have applied a
      range of fluorescent lipophilic probes to live mycobacteria, including
      Mycobacterium smegmatis, Mycobacterium tuberculosis, Mycobacterium avium,
      Mycobacterium gadium and Mycobacterium aurum, and analysed the resultant signals
      by fluorescence microscopy and digital image processing. Five key features were
      observed: (i) the presence of both envelope and intracellular lipid domains; (ii)
      differential localization of probes into these domains influenced predominantly
      by their hydrophobicity, as modelled by their calculated octanol:water partition
      coefficients and by their amphiphilicities; (iii) uneven distribution of
      lipophilic material in the envelope; (iv) selective labelling of septal regions
      of the envelope; and (v) modification of labelling patterns by additional
      treatments such as fluorescence quenching antibodies, detergents and solvents.
      Using this last approach, a coherent cell envelope lipid domain was demonstrated
      outside the cytoplasmic membrane and, for the first time, the proposed covalently
      linked mycolyl-arabinogalactan-peptidoglycan macromolecular complex was imaged
      directly. The use of fluorescent probes and high-resolution fluorescence
      microscopy has enabled us to obtain a coherent view of distinct lipid domains in
      mycobacteria. Further application of this approach will facilitate understanding
      of the role of lipids in the physiology of these organisms.

PMID- 10200975
TI  - Normalized nucleotide frequencies allow the definition of archaeal promoter
      elements for different archaeal groups and reveal base-specific TFB contacts
      upstream of the TATA box.

PMID- 10200974
TI  - Inactivation of the antigen 85C gene profoundly affects the mycolate content and
      alters the permeability of the Mycobacterium tuberculosis cell envelope.
AB  - The antigen 85 complex of Mycobacterium tuberculosis consists of three abundantly
      secreted proteins. The recent characterization of a mycoloyltransferase activity
      associated in vitro with each of these antigens suggested that they are
      potentially important for the building of the unusual cell envelope of
      mycobacteria. To define the physiological role of these proteins, the gene coding
      for antigen 85C was inactivated by transposon mutagenesis. The resulting mutant
      was shown to transfer 40% fewer mycolates to the cell wall with no change in the
      types of mycolates esterifying arabinogalactan or in the composition of non
      covalently linked mycolates. As a consequence, the diffusion of the hydrophobic
      chenodeoxycholate and the hydrophilic glycerol, but not that of isoniazid, was
      found to be much faster through the cell envelope of the mutant than that of the
      parent strain. Taken together, these data demonstrate that: (i) antigen 85C is
      involved directly or indirectly in the transfer of mycolates onto the cell wall
      of the whole bacterium; (ii) the enzyme is not specific for a given type of
      mycolate; and (iii) the cell wall-linked mycolate layer may represent a barrier
      for the diffusion of small hydrophobic and hydrophilic molecules.

PMID- 10200976
TI  - Metabolite-induced metabolons: the activation of transporter-enzyme complexes by
      substrate binding.

PMID- 10200977
TI  - A unique short signal sequence in membrane-anchored proteins of Archaea.

PMID- 10200978
TI  - The Escherichia coli haemolysin secretion apparatus: a potential universal
      antigen delivery system in gram-negative bacterial vaccine carriers.

PMID- 10200979
TI  - Evolution of conjugative plasmids from gram-positive bacteria.

PMID- 10200980
TI  - A class of integral membrane proteins will be overlooked by the 'proteome' study
      that is based on two-dimensional gel electrophoresis.

PMID- 10200981
TI  - New insights into the molecular pathophysiology of polycystic kidney disease.
AB  - Polycystic kidney diseases are characterized by the progressive expansion of
      multiple cystic lesions, which compromise the function of normal parenchyma.
      Throughout the course of these diseases, renal tubular function and structure are
      altered, changing the tubular microenvironment and ultimately causing the
      formation and progressive expansion of cystic lesions. Renal tubules are
      predisposed to cystogenesis when a germ line mutation is inherited in either the
      human PKD1 or PKD2 genes in autosomal dominant polycystic kidney disease (ADPKD)
      or when a homozygous mutation in Tg737 is inherited in the orpk mouse model of
      autosomal recessive polycystic kidney disease (ARPKD). Recent information
      strongly suggests that the protein products of these disease genes may form a
      macromolecular signaling structure, the polycystin complex, which regulates
      fundamental aspects of renal epithelial development and cell biology. Here, we re
      examine the cellular pathophysiology of renal cyst formation and enlargement in
      the context of our current understanding of the molecular genetics of ADPKD and
      ARPKD.

PMID- 10200982
TI  - Th1 and Th2 T helper cell subsets affect patterns of injury and outcomes in
      glomerulonephritis.
AB  - The recognition that human immune responses can be directed by two different
      subsets of T helper cells (Th1 and Th2) has been an important development in
      modern immunology. Immune responses polarized by either the Th1 or Th2 subset
      predominance result in different inflammatory effector pathways and disease
      outcomes. Many autoimmune diseases are associated with either Th1- or Th2-
      polarized immune responses. Although these different immune response patterns are
      relevant to glomerulonephritis (GN), little attention has been paid to the
      consequences of Th1 or Th2 predominance of nephritogenic immune responses for the
      pattern and outcome of GN. Unlike other autoimmune conditions, GN results from a
      variety of different immune responses and has a range of histologic features and
      immune effectors in glomeruli. This review assesses the data available from
      studies of experimental and human GN that address the Th1 or Th2 predominance of
      nephritogenic immune responses and their relevance to the different
      histopathological patterns and outcomes of GN. In particular, the evidence that
      Th1-predominant nephritogenic immune responses are associated with severe
      proliferative and crescentic GN is presented.

PMID- 10200983
TI  - Identification of COL4A5 defects in Alport's syndrome by immunohistochemistry of
      skin.
AB  - BACKGROUND: The COL4A3-COL4A4-COL4A5 network in the glomerular basement membrane
      is affected in the inherited renal disorder Alport's syndrome (AS). Approximately
      85% of the AS patients are expected to carry a mutation in the X-chromosomal
      COL4A5 gene and 15% in the autosomal COL4A3 and COL4A4 genes. The COL4A5 chain is
      also present in the epidermal basement membrane (EBM). It is predicted that
      approximately 70% of the COL4A5 mutations prevent incorporation of this chain in
      basement membranes. METHODS: We investigated whether or not COL4A5 defects could
      be detected by immunohistochemical analysis of the EBM. Punch skin biopsies were
      obtained from 22 patients out of 17 families and two biopsy specimens from
      healthy males were used as controls. RESULTS: In four cases with the COL4A5
      frameshift or missense mutations, the COL4A5 chain was either lacking from the
      EBM (male) or showed a focally negative pattern (female). In three other patients
      with a COL4A5 missense mutation, a COL4A3 and a COL4A4 mutation, respectively,
      the COL4A5 staining was normal. A (focally) negative EBM-COL4A5 staining was
      found in three patients of six families with a diagnosis of AS and in one family
      of a group of four families with possible AS. CONCLUSIONS: The (focal) absence of
      COL4A5 in the EBM of skin biopsy specimens can be used for fast identification of
      COL4A5 defects. Combined with polymorphic COL4A5 markers, both postnatal and
      prenatal DNA diagnosis are possible in the family of the patient.

PMID- 10200984
TI  - Mutational analysis within the 3' region of the PKD1 gene.
AB  - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is one of the
      most common genetic diseases in humans, affecting 1 out of 1000 individuals. At
      least three different genes are involved in this disease. The search for
      mutations in PKD1 is complicated because most of the transcript is encoded by a
      genomic region reiterated more proximally on chromosome 16, and no prevalent
      mutation has been reported. METHODS: We have screened DNA from exon 43 through
      exon 46 and intron 40 of the PKD1 sequence by single-stranded conformational
      polymorphism (SSCP) analysis in 175 ADPKD patients. RESULTS: We have found 25
      differences with respect to the reported PKD1 DNA sequence, seven of which are
      mutations (Q4041X, Q4124X, IVS44-1G-->C, IVS45-1G-->A, 12801del28, R4275W, and
      Q4224P). We found different phenotypical expressions of the same mutation in the
      families studied. We have detected several common polymorphisms, and some of them
      cosegregate, suggesting a common origin of these alleles in PKD1. CONCLUSIONS:
      The detection of only seven mutations in 175 unrelated ADPKD patients for this
      region of the PKD1 analyzed suggests that mutations could be widespread
      throughout all of the gene and that a prevalent mutation is not expected to
      occur. The identified PKD1 missense mutations may help to refine critical regions
      of the protein. Until a quicker and more sensitive method for the detection of
      mutations becomes available, linkage studies will continue to be the basis for
      the molecular diagnosis of ADPKD families.

PMID- 10200985
TI  - Gene therapy for renal anemia in mice with polycystic kidney using an adenovirus
      vector encoding the human erythropoietin gene.
AB  - BACKGROUND: Recombinant human erythropoietin (rHuEPO) is primarily used for
      patients with anemia associated with end-stage renal disease. We evaluated the
      efficacy of EPO gene therapy using adenovirus vector for chronic renal failure
      mice expressing severe renal anemia. METHODS: Recombinant HuEPO gene transfer to
      mesothelial cells was performed in vitro and in vivo. Recombinant replication
      deficient adenoviruses containing rHuEPO cDNA (AdCMVEPO), E. coli lacZ gene
      (AdCMVlacZ), or an nonexogenous gene (AdNull as control vector) driven by the
      cytomegalovirus promotor/enhancer were constructed. The oligosaccharides
      associated with the rHuEPO from AdCMVEPO-treated mesothelial cells were analyzed.
      For in vivo study, the DBA/2FG-pcy mouse, a model for human autosomal recessive
      polycystic kidney disease resulting in chronic renal failure with progressive
      anemia, was used. RESULTS: The sialylated oligosaccharides associated with the
      rHuEPO produced in AdCMVEPO-treated mesothelial cells occupied 78 +/- 0.7% of the
      total oligosaccharide pool. A single intraperitoneal administration of AdCMVEPO
      induced rHuEPO synthesis in the peritoneal cells and a marked increase in
      erythrocyte production. The maximal increase in hematocrit (43 +/- 4%) was
      observed on day 28, and it remained elevated for 40 days. CONCLUSION: These
      results indicate that intraperitoneal administration of AdCMVEPO improves renal
      anemia in mice with chronic renal failure and that the mesothelial cell is an
      appropriate target cell for gene transfer.

PMID- 10200986
TI  - Clinical and genetic heterogeneity in familial focal segmental
      glomerulosclerosis. International Collaborative Group for the Study of Familial
      Focal Segmental Glomerulosclerosis.
AB  - BACKGROUND: Familial forms of focal segmental glomerulosclerosis (FFSGS) that
      exhibit autosomal dominant or recessive patterns of inheritance have been
      described. The genetic basis of these hereditary forms of FSGS is unknown. One
      recent study of a kindred from Oklahoma with an autosomal dominant form of FSGS
      linked this disease to a region of chromosome 19q. In addition, polymorphisms in
      a gene in this region on chromosome 19q13 have been linked to congenital
      nephrotic syndrome of the Finnish type. We have ascertained and characterized a
      large family with autosomal dominant FFSGS (Duke 6530). METHODS: Families were
      compared for clinical and genetic heterogeneity. To test for linkage of our
      family to this portion of chromosome 19, genomic DNA was isolated from 102 family
      members, and polymerase chain reaction was performed using eight microsatellite
      markers that spanned the area of interest on chromosome 19. Data were evaluated
      using two-point linkage analysis, multipoint analysis, and an admixture test.
      RESULTS: Linkage was excluded at a distance of +/- 5 to 10 CM for all markers
      tested with two-point log10 of the odds of linkage (LOD) scores and from an
      approximate 60 CM interval in this area of chromosome 19q via multipoint
      analysis. CONCLUSIONS: FSGS has been called the "final common pathway" of
      glomerular injury, as it is a frequent pathological manifestation with diverse
      etiologies. This diversity likely correlates with the genetic heterogeneity that
      we have established. Thus, our data demonstrate that there are at least two genes
      responsible for this disease, and there is genetic as well as clinical
      heterogeneity in autosomal dominant FSGS.

PMID- 10200987
TI  - Increased frequency of G-protein beta 3-subunit 825 T allele in dialyzed patients
      with type 2 diabetes.
AB  - BACKGROUND: A polymorphism (C825T) in exon 10 of the gene encoding the beta 3
      subunit of heterotrimeric G proteins (GN beta 3) has recently been described, and
      the T allele was found to be associated with late-onset hypertension. Because
      hypertension is a known risk factor for the development of clinically manifest
      progressive renal disease, we examined the C825T polymorphism in older
      hemodialysis patients suffering from nondiabetic renal disease or type 2 diabetes
      with presumed diabetic nephropathy, respectively, and in older healthy controls.
      METHODS: Genotyping was performed by polymerase chain reaction, followed by
      restriction enzyme analysis. RESULTS: The study showed that the frequency of the
      T allele in the nondiabetic patients on dialysis (0.232) was significantly (P <
      0.03) lower than in older healthy controls (0.293). In contrast, the frequency
      was significantly (P < 0.02) higher in older patients with type 2 diabetes on
      dialysis. No significant change in T-allele frequency was noted in older patients
      with type 2 diabetes without microangiopathy (0.286). The odds ratios for
      patients with type 2 diabetes on dialysis versus nondiabetic patients on dialysis
      were 3.24 (1.3 to 7.9, P < 0.00079) for TT/CC and 1.82 (1.07 to 3.09, P < 0.02)
      for CT/CC. The respective odds ratios for patients with type 2 diabetes on
      dialysis versus controls were 2.05 (1.07 to 3.9, P < 0.028) for CT/CC and 1.216
      (0.79 to 1.87; P < 0.37) for CT/CC. CONCLUSION: The data do not support a role of
      the hypertension-associated T allele in the genesis of dialysis-dependent end
      stage renal failure in general, but are compatible with a specific role of the T
      allele in the development or progression of diabetic nephropathy.

PMID- 10200988
TI  - Endothelial cells regulate proximal tubule epithelial cell sodium transport.
AB  - BACKGROUND: Proximal tubule epithelial cells are in close contact with the renal
      microvasculature, but the effect of endothelial cells (ECs) on proximal tubule
      epithelial cell (PTEC) function is not known. METHODS: To determine if ECs
      regulate PTECs, we coincubated ECs with PTECs in a system that permitted cross
      talk between the two cell types and the vectorial transport of sodium. RESULTS:
      In the presence (but not absence) of ECs, adding bradykinin or acetylcholine
      increased cGMP and decreased sodium transport, as well as Na,K-ATPase in PTECs.
      Interleukin (IL)1B preconditioning of ECs also increased cGMP and decreased
      sodium transport and Na,K-ATPase in PTECs. Bradykinin, acetylcholine, and IL1B EC
      dependent effects were reversed with the nitric oxide (NO) synthase inhibitor L
      NNA. In the absence of ECs, the addition of NO donors to PTECs increased cGMP and
      decreased sodium transport and Na,K-ATPase. 8Br-cGMP also decreased PTEC sodium
      transport and Na,K-ATPase. CONCLUSION: Endothelial cells regulate PTEC function.
      This effect is mediated by NO synthase-dependent up-regulation of cGMP in PTECs.

PMID- 10200989
TI  - Hypoxia-induced adrenomedullin production in the kidney.
AB  - BACKGROUND: Adrenomedullin (AM) is a newly discovered peptide that has a potent
      vasorelaxant activity. To investigate its potential roles in hypoxia-induced
      renal injury, we examined whether AM production in the kidney increased under
      hypoxic conditions. METHODS: The AM transcript levels in Madin-Darby canine
      kidney (MDCK) cells, rat vascular smooth muscle cells (VSMCs), and rat mesangial
      cells were assessed by Northern blot analyses under normoxic and hypoxic
      conditions. The AM peptide in culture media was measured by radioimmunoassay. The
      effects of hypoxia on accumulation of cAMP in VSMCs were also examined. The
      stability of AM transcripts under normoxic and hypoxic conditions was compared in
      the presence of actinomycin D. The effects of hypoxia on AM promoter activity was
      assessed by transient transfection assays using the AM promoter subcloned
      upstream of luciferase gene. RESULTS: The expression of AM transcripts increased
      significantly in MDCK cells, rat VSMCs, and rat mesangial cells under hypoxic
      conditions without changes in the stability of AM transcripts; however, the AM
      promoter activity under hypoxic was not elevated significantly. The accumulation
      of AM peptide in culture media also increased significantly under hypoxic
      conditions in MDCK cells (2.2 +/- 0.1 fmol/10(5) cells in normoxia vs. 3.5 +/-
      0.3 fmol/10(5) cells in hypoxia, 6 hr after hypoxia induction, P < 0.001), and in
      rat VSMCs (5.5 +/- 0.3 fmol/10(5) cells in normoxia vs. 7.8 +/- 0.4 fmol/10(5)
      cells in hypoxia, 8 hr after hypoxia induction, P < 0.01). Under hypoxic
      conditions, cAMP levels in rat VSMCs increased significantly compared with those
      under normoxic conditions (13.3 +/- 1.4 pmol/well vs. 4.6 +/- 0.4 pmol/well, P <
      0.01). CONCLUSIONS: Renal parenchymal cells as well as renal vessels may produce
      AM under hypoxic conditions.

PMID- 10200990
TI  - Estradiol suppresses type I collagen synthesis in mesangial cells via activation
      of activator protein-1.
AB  - BACKGROUND: Estradiol suppresses the synthesis of type I collagen by murine
      mesangial cells. However, neither the alpha 1(I) nor the alpha 2(I) collagen gene
      contains an estrogen-response element. Because estradiol modulates the
      transcription of several genes that lack an estrogen-response element but contain
      a regulatory activator protein-1 (AP-1) binding motif, we hypothesized that AP-1
      may mediate estradiol-induced suppression of type I collagen synthesis. METHODS:
      We measured type I collagen synthesis in murine mesangial cells exposed to
      estradiol, phorbol 12-myristate 13-acetate (an activator of AP-1), or curcumin
      (an inhibitor of AP-1). We also assessed the effects of estradiol on the steady
      state level of c-fos and c-jun mRNA and on the binding of mesangial cell nuclear
      extracts to an AP-1 consensus binding site oligonucleotide. RESULTS: Estradiol
      (10(-10) M to 10(-7) M) suppressed type I collagen synthesis by murine mesangial
      cells in a dose-dependent manner (10(-7) M, 43.7 +/- 8.2% of control values, P <
      0.001). Phorbol 12-myristate 13-acetate (10 microM, four-hr exposure) also
      decreased type I collagen in the media. In contrast, curcumin (1 microM)
      increased type I collagen. Estradiol increased the steady-state level of c-fos
      mRNA twofold at 30 minutes, with a return to basal levels at one hour. This was
      associated with a greater than threefold increase in the binding of nuclear
      extracts from estradiol-treated mesangial cells to an AP-1 consensus binding site
      oligonucleotide. Estradiol-enhanced binding of nuclear extracts to the AP-1
      oligonucleotide was reversed by cycloheximide. CONCLUSIONS: These data suggest
      that estradiol suppresses collagen I synthesis by murine mesangial cells via
      enhanced AP-1 activity.

PMID- 10200991
TI  - Angiotensin II inhibits interleukin-1 beta-induced nitric oxide production in
      cultured rat mesangial cells.
AB  - BACKGROUND: Macrophage-type nitric oxide synthase (NOS-II) is expressed in
      glomerular mesangial cells in response to inflammatory cytokines. Nitric oxide
      (NO) has antithrombotic and cytostatic activities in glomerular diseases. Recent
      studies have suggested that several vasoactive substances and growth factors
      modulate NO production in a tissue-specific manner. The aim of this study was to
      examine whether angiotensin II and transforming growth factor-beta (TGF-beta)
      modulate cytokine-stimulated NO production and NOS-II gene expression in rat
      glomerular mesangial cells. METHODS: Cultured rat mesangial cells were incubated
      with interleukin-1 beta (IL-1 beta) for 24 hours. The effects of angiotensin II
      and TGF-beta on stimulated nitrite accumulation and NOS-II mRNA levels were
      determined. RESULTS: Angiotensin II and TGF-beta significantly decreased IL-1
      beta-stimulated nitrite accumulation. The angiotensin type 1 receptor antagonist
      CV11974 prevented angiotensin II-mediated inhibition of NO production. TGF-beta
      neutralizing antibody reversed the effect of TGF-beta without affecting
      angiotensin II-mediated inhibition of NO production. TGF-beta markedly decreased
      steady-state levels of NOS-II mRNA and the half-life of the message, whereas
      angiotensin II did not alter these parameters. CONCLUSIONS: These results suggest
      that in mesangial cells, angiotensin II and TGF-beta participate in the
      inhibitory regulation of cytokine-induced NO production. TGF-beta inhibits NO
      production by decreasing NOS-II mRNA levels, whereas angiotensin II may regulate
      NO production at the levels after NOS-II gene expression. An autocrine action of
      TGF-beta induced by angiotensin II is unlikely to contribute to angiotensin II
      mediated inhibition of NO production.

PMID- 10200992
TI  - Decreased calcium-sensing receptor expression in hyperplastic parathyroid glands
      of uremic rats: role of dietary phosphate.
AB  - BACKGROUND: The abnormal control of parathyroid hormone secretion in chronic
      renal failure is attributed, in part, to down-regulation of the calcium-sensing
      receptor (CaR) in hyperplastic parathyroid tissue. The cause of this down
      regulation is unknown. Here we examined the roles of uremia and parathyroid
      hyperplasia on parathyroid gland (PTG) CaR expression in the rat model of renal
      failure. METHODS: Rats made uremic by 5/6 nephrectomy were maintained for one
      month on diets containing 0.2% P (low phosphate), 0.5% P (normal phosphate) or
      1.2% P (high phosphate); intact rats (controls) were maintained on the normal
      phosphate diet. RESULTS: CaR mRNA was reduced only in uremic rats fed the high
      phosphate diet (55% less than in controls, P < 0.05). Immunohistochemical
      staining revealed decreased CaR protein expression in uremic high-phosphate rat
      PTG compared with controls (41% decrease as determined by computer-assisted
      quantitation, P < 0.01). PTG size was increased in uremic rats fed the high
      phosphate diet compared with controls (2.77 +/- 0.95 vs. 0.77 +/- 0.16
      microgram/g body wt, P < 0.0001). There was no increase in PTG size in uremic
      rats fed the low-phosphate and normal-phosphate diets (0.92 +/- 0.31 and 1.01 +/-
      0.31 micrograms/g) compared with controls (0.77 +/- 0.16 microgram/g body wt).
      Immunohistochemical staining for proliferating cell nuclear antigen in
      hyperplastic PTG from uremic rats showed that CaR was decreased primarily in
      areas of active cell proliferation. CONCLUSION: These results suggest that CaR
      down-regulation cannot be attributed to uremia per se, but rather, is associated
      with parathyroid cell proliferation. Furthermore, dietary phosphate restriction
      prevents both the parathyroid hyperplasia and decreased CaR expression in renal
      failure.

PMID- 10200993
TI  - Mesangial cells from diabetic NOD mice constitutively express increased density
      of atrial natriuretic peptide C receptors.
AB  - BACKGROUND: Experimental evidence shows that natriuretic peptides (NPs) play a
      pathophysiological role in the glomerular hemodynamic abnormalities that occur in
      diabetes mellitus. METHODS: In this study, the cGMP response to NPs and the
      different subtypes of NP receptors were examined in mesangial cells derived from
      a genetic model of diabetes, the nonobese diabetic (NOD) mouse. Multiple
      mesangial cell lines were derived from diabetic (D-NOD) and nondiabetic (ND-NOD)
      adult mice and were studied at different passages. RESULTS: cGMP accumulation
      after stimulation by atrial NP (ANP) or C-type NP (CNP) was markedly inhibited in
      D-NOD cells irrespective of the glucose concentration (6 or 20 mM) in the culture
      medium. In contrast, NP receptor density measured from [125I]-ANP saturation
      binding curves was 7.5 times greater in D-NOD than in ND-NOD cells. No change in
      KD (200 pM in both cell lines) was observed. Competitive inhibition studies
      showed that 4-23 C-ANP, which is specific of clearance receptors (NPR-C),
      displaced 90% of the maximum fraction bound, suggesting the predominance of NPR-C
      in both cell lines. Further identification was obtained from RNase protection
      assay and reverse transcription-polymerase chain reaction, which also
      demonstrated the higher expression of NPR-C mRNA in D-NOD cells. In contrast, NPR
      A mRNA was not modified. Increased expression of NPR-C in D-NOD cells was
      associated with an increase of ANP internalization rate at 37 degrees C,
      indicating that these receptors were functional. CONCLUSIONS: These studies
      demonstrate that the constitutive overexpression of NPR-C in D-NOD mesangial
      cells is associated with a decreased response of cGMP to ANP or CNP treatment.
      This could be due to the lesser availability of the peptides for binding to NPR-A
      or NPR-B or to an inhibitory effect on NP-dependent guanylate cyclase activity
      via the activation of NPR-C.

PMID- 10200994
TI  - Mechanisms of induction of renal allograft tolerance in CD45RB-treated mice.
AB  - BACKGROUND: Rejection is the most significant problem in the field of
      transplantation. The current goal of transplant immunology is to develop better
      immunotherapeutic protocols that are aimed at specifically suppressing
      alloreactivity and preserving an otherwise intact immune system. We have
      previously shown that mice will accept renal allografts indefinitely with normal
      renal function after two injections of a monoclonal antibody to the CD45RB
      protein. Furthermore, this antibody will reverse acute rejection when therapy is
      delayed until day 4 and will still induce tolerance. The mechanisms of this
      therapeutic benefit are not known. METHODS: BALB/C mice were used as recipients
      of major multiple histocompatibility complex-mismatched kidneys using C57BL/6 as
      donors. Immunoperoxidase microscopy and Northern blots for cytokine gene
      expression were used to study the renal allografts. Fluorescence-activated cell
      sorter (FACS) analyses of peripheral blood lymphocytes were performed.
      Phosphotyrosine peptide phosphatase assays were performed on splenic lymphocyte
      membranes. RESULTS: A CD45RB monoclonal antibody (MB23G2) induced tolerance and
      partially depletes peripheral blood lymphocytes. A therapeutically ineffective
      CD45RB monoclonal antibody (MB4B4) merely coated the circulating lymphocytes.
      Furthermore, MB23G2 stimulated more tyrosine phosphatase activity than MB4B4 in
      mouse T-cell membranes. CONCLUSIONS: The clearance of peripheral blood lymphocyte
      populations and stimulation of protein tyrosine phosphatase activity may be
      important in the mechanism of tolerance induction by CD45RB therapy, which may be
      clinically relevant in the therapy of organ rejection in humans.

PMID- 10200995
TI  - Tissue factor pathway inhibitor expression in human crescentic
      glomerulonephritis.
AB  - BACKGROUND: Tissue factor (TF) pathway inhibitor (TFPI), the major endogenous
      inhibitor of extrinsic coagulation pathway activation, protects renal function in
      experimental crescentic glomerulonephritis (GN). Its glomerular expression and
      relationship to TF expression and fibrin deposition in human crescentic GN have
      not been reported. METHODS: Glomerular TFPI, TF, and fibrin-related antigen (FRA)
      expression were correlated in renal biopsies from 11 patients with crescentic GN.
      Biopsies from 11 patients with thin basement membrane disease and two normal
      kidneys were used as controls. RESULTS: TFPI was undetectable in control
      glomeruli but was detectable in interstitial microvessels. In crescentic
      biopsies, TFPI was detected in cellular crescents and was more prominent in
      fibrous/fibrocellular crescents, indicating a correlation with the chronicity of
      crescentic lesions. TFPI appeared to be associated with macrophages but not
      endothelial or epithelial cells. TFPI was generally undetectable in regions of
      the glomerular tuft with minimal damage. In contrast, TF and FRA were strongly
      expressed in regions of minimal injury, as well as in more advanced proliferative
      and necrotizing lesions. Despite prominent TF expression, FRA was less prominent
      in fibrous/fibrocellular crescents in which TFPI expression was maximal.
      CONCLUSIONS: These data suggest that TFPI is strongly expressed in the later
      stages of crescent formation and is inversely correlated with the presence of FRA
      in human crescentic GN. This late induction of TFPI may inhibit TF activity and
      favor reduced fibrin deposition in the chronic stages of crescent formation.

PMID- 10200996
TI  - Interleukin-4 ameliorates crescentic glomerulonephritis in Wistar Kyoto rats.
AB  - BACKGROUND: Activated macrophages play a central role in crescentic
      glomerulonephritis. Interleukin-4 (IL-4) down-regulates many macrophage
      proinflammatory activities. We therefore studied the effect of IL-4 on glomerular
      injury in a model of crescentic glomerulonephritis in the Wistar Kyoto rat.
      METHODS: Glomerulonephritis was induced by i.v. administration of rabbit antirat
      glomerular basement membrane antiserum (nephrotoxic serum, NTS). In experiment 1,
      IL-4 was given from two hours before NTS until day 6. In experiment 2, rats were
      treated from day 0 to 7 and were then monitored until killed on day 28. In
      experiment 3, IL-4 was given from day 4 to 7. RESULTS: Continuous IL-4 treatment
      (experiment 1) significantly (P = 0.001) reduced proteinuria (3 +/- 1 mg per 24
      hr vs. 56 +/- 7), fibrinoid necrosis (0.06 +/- 0.04 quadrants/glomulus vs. 1.2 +/
      0.1), macrophage infiltration (6.7 +/- 2.6 cells/glom vs. 33 +/- 2.5), CD8+
      cells (1.5 +/- 0.6 cells/glom vs. 6.2 +/- 1.1), inducible nitric oxide synthase
      positive cells (0.04 +/- 0.04 cells/glom vs. 3.7 +/- 0.6), proliferating cell
      nuclear antigen positive cells (3.2 +/- 1 cells/glom vs. 15 +/- 2.3), and
      glomerular intercellular adhesion molecule-1 expression. Follow-up after seven
      days of treatment (experiment 2) showed that at four weeks, creatinine clearance
      was higher in treated rats (1.1 +/- 0.1 ml/min vs. 0.4 +/- 01, P = 0.011), and
      both glomerular scarring (P = 0.006) and tubular atrophy (P = 0.006) were less.
      Delayed treatment (experiment 3) reduced proteinuria (41 +/- 5 mg per 24 hr vs.
      97 +/- 9, P = 0.004) and fibrinoid necrosis (0.39 +/- 0.05 quadrants/glom vs. 1.6
      +/- 0.1, P = 0.004). There was no difference in macrophage infiltration, but
      inducible nitric oxide synthase positive cells were reduced (0.6 +/- 0.1
      cells/glom vs. 1.8 +/- 0.4, P = 0.01) as were ED3+ cells (0.18 +/- 0.06
      cells/glom vs. 1.86 +/- 0.21, P = 0.004). CONCLUSION: In this model of crescentic
      glomerulonephritis, early IL-4 treatment abolished proteinuria and markedly
      reduced glomerular inflammation. If treatment was stopped after seven days, there
      was continuing benefit on glomerular and tubulointerstitial scarring and
      creatinine clearance at four weeks. If treatment was delayed until inflammation
      was established, there was still a reduction of injury, but without an alteration
      of macrophage numbers, suggesting that IL-4 may be acting, in part, to reduce
      macrophage activation.

PMID- 10200997
TI  - Unilateral ureteral obstruction impairs renal antioxidant enzyme activation
      during sodium depletion.
AB  - BACKGROUND: Obstructive nephropathy leads to progressive renal tubular atrophy
      and interstitial fibrosis and is associated with sodium wasting and sodium
      depletion. Renal damage resulting from unilateral ureteral obstruction (UUO) may
      be aggravated by reactive oxygen species (ROS), which are produced by a variety
      of processes. Ideally, deleterious effects of ROS are attenuated by antioxidant
      enzymes, including the superoxide dismutases, glutathione peroxidases, catalase,
      and glutathione-S-transferases. The general paradigm is that tissue damage occurs
      when ROS production is greater than the protective capacity of the antioxidant
      enzymes. METHODS: This study was designed to investigate the response of renal
      antioxidant enzymes to UUO and sodium depletion. Adult, male Sprague-Dawley rats
      received normal-sodium or sodium-depleted siets and were subjected to UUO or sham
      operation. Obstructed (UUO), intact opposite, or sham-operated kidneys were
      harvested after 14 days, and antioxidant enzyme activities were measured in
      kidney homogenates. Thiobarbituric acid reactive substances were measured in
      these homogenates at 3 and 14 days after UUO or sham operation as an index of ROS
      production. RESULTS: Renal interstitial area, a measure of fibrosis, was
      increased by UUO and was doubled in sodium-depleted animals. Sodium depletion
      increased manganese superoxide dismutase, glutathione peroxidases, and
      glutathione-S-transferase activities in sham-operated kidneys but not in UUO
      kidneys. Relative to intact opposite kidneys, UUO kidneys had reduced activities
      of catalase, manganese superoxide dismutase, and glutathione-S-transferase in
      normal-sodium animals and all antioxidant enzymes tested in sodium-depleted
      animals. Renal thiobarbituric acid reactive substances were increased by three
      days of UUO and were increased further by 14 days of sodium depletion.
      CONCLUSION: In summary, sodium depletion increased several renal antioxidant
      enzymes, consistent with a stress response to increased ROS production. Further,
      UUO not only reduced antioxidant enzyme activities but also inhibited increases
      seen with sodium depletion. We conclude that suppression of renal antioxidant
      enzyme activities by UUO contributes to the progression of renal injury in
      obstructive nephropathy, a process exacerbated by sodium depletion.

PMID- 10200998
TI  - Induction of albuminuria in mice: synergistic effect of two monoclonal antibodies
      directed to different domains of aminopeptidase A.
AB  - BACKGROUND: Aminopeptidase A is an enzyme that is present on podocytes and is
      involved in the degradation of angiotensin II. In previous studies in mice, we
      administered single monoclonal antibodies directed against aminopeptidase A. We
      observed that only monoclonal antibodies that inhibited aminopeptidase A enzyme
      activity caused albuminuria. METHODS: In this study, the effects of the combined
      injections of two monoclonal anti-aminopeptidase A antibodies (mAbs) were
      studied, using a combination of anti-aminopeptidase A mAbs that were directed
      against two different domains involved in the aminopeptidase A enzyme activity
      (ASD-3 or ASD-37) and an anti-aminopeptidase A mAb not related to the enzyme
      active site (ASD-41). RESULTS: An injection of the combinations ASD-3/37 (total 4
      mg, 1:1 ratio) and ASD-37/41 (total 4 mg, 1:1 ratio) in doses that do not cause
      albuminuria when given alone (4 mg) induced massive albuminuria at day 1 after
      injection. The combination ASD-3/41 had no effect. This albuminuria was not
      dependent on systemic immune mediators of inflammation and could not merely be
      related to a blockade of aminopeptidase A enzyme activity. However, a correlation
      was observed between the induction of albuminuria and the aggregation of the mAbs
      injected and aminopeptidase A on the podocytes. An injection of the combinations
      ASD-3/37 or ASD-37/41 did not cause an increase in systemic blood pressure. The
      treatment with a combination of enalapril and losartan lowered blood pressure (53
      +/- 10 vs. 90 +/- 3 mm Hg in untreated mice) and reduced the acute albuminuria by
      55% (11,145 +/- 864 vs. 24,517 +/- 2448 micrograms albumin/18 hr in untreated
      mice). However, similar effects were observed using triple therapy. Therefore,
      the reduction of albuminuria by the combined treatment of enalapril/losartan
      seems to be the consequence of the reduction in the systemic blood pressure.
      These findings argue against a specific role for angiotensin II in this model.
      CONCLUSIONS: The combined injection of two mAbs directed against different
      domains of aminopeptidase A induces a massive albuminuria in mice, which is not
      merely dependent on angiotensin II. We hypothesize that the direct binding of
      mAbs to at least two pathogenic domains on aminopeptidase A triggers the podocyte
      to release mediators that are involved in the observed albuminuria.

PMID- 10200999
TI  - Role of free radicals in the pathogenesis of lipid-induced glomerulosclerosis in
      rats.
AB  - BACKGROUND: We examined whether a high-cholesterol (HC) diet causes
      glomerulosclerosis in rats, and investigated the role of free radicals and lipid
      peroxidation in lipid-induced glomerulosclerosis. METHODS: The rats were given a
      normal diet, a HC diet, or a HC diet with antioxidants and radical scavengers.
      Serum levels of lipid, lipid peroxide (LOOH), urinary excretion of protein (UP),
      and urinary norepinephrine excretion (UNE) were measured. The glomerular
      sclerosing score was used to evaluate the renal injury. RESULTS: Blood pressure,
      total cholesterol, and LOOH were increased by a HC diet, as were UP and UNE. The
      HC diet induced renal injury. Treatment with superoxide dismutase,
      dimetylthiourea as a scavenger of hydroxyl radical (OH.), defferoxamine masilate
      as an iron chelator, or vitamin E inhibited the increases in blood pressure,
      LOOH, UP, and UNE, whereas total cholesterol was not affected. The production of
      superoxide anion (O2-.) by neutrophil and LOOH in the kidney was increased, and
      superoxide dismutase and hydrogen peroxide in the kidney were decreased. Almost
      all of these changes were attenuated by vitamin E; however, the O2-. production
      was not inhibited. OH. was increased by the HC diet, and it was normalized with
      the treatments. Furthermore, the sclerosing score was partially suppressed by the
      treatments. Ferric iron was stained in the proximal tubulus, and it was not
      observed in the treated rats. CONCLUSIONS: The data suggest that lipid
      peroxidation is involved in the pathogenesis of lipid-induced glomerulosclerosis
      and that O2-. and OH. may play a role in the process.

PMID- 10201000
TI  - Lipoprotein(a) stimulates growth of human mesangial cells and induces activation
      of phospholipase C via pertussis toxin-sensitive G proteins.
AB  - BACKGROUND: Renal disease is commonly associated with hyperlipidemia and
      correlates with glomerular accumulation of atherogenic lipoproteins, for example,
      lipoprotein(a) [Lp(a)], and mesangial hypercellularity. Specific binding of Lp(a)
      to mesangial cells and induction of c-myc and c-fos expression has been
      demonstrated. Therefore, in this study, we investigated a possible growth
      stimulatory effect and mode of action of Lp(a) in human mesangial cells. METHODS:
      Lp(a) was purified from the regenerate fluid of a dextran sulfate column-based
      low-density lipoprotein apheresis system. Human mesangial cells were isolated by
      a sequential sieving technique from patients undergoing tumor nephrectomy. DNA
      synthesis was measured by [3H]-thymidine incorporation. The intracellular calcium
      concentration ([Ca2+]i) was determined by Fura 2-fluorescence, and inositol 1,4,5
      trisphosphate (1,4,5-IP3) concentration was measured by a radioreceptor assay.
      RESULTS: The data show that Lp(a) bound to the cells with a Kd of 17.0
      micrograms/ml and increased DNA synthesis and cell proliferation. Lp(a) caused a
      rapid increase in 1,4,5-IP3 and [Ca2+]i via a pertussis toxin-sensitive
      mechanism. The phospholipase C (PLC) inhibitor U73122 abolished Lp(a)-induced
      cell proliferation. In contrast, vasopressin-induced increase in 1,4,5-IP3 and
      [Ca2+]i was pertussis toxin insensitive. CONCLUSION: This study revealed that
      Lp(a) stimulates growth of human mesangial cells. Lp(a)-induced signaling
      involves binding to a receptor and stimulation of PLC via Gi proteins.
      Stimulation of PLC appears to be essential for the growth stimulatory effect of
      Lp(a). Whether these effects of Lp(a) contribute to the pathophysiology of renal
      disease needs to be determined.

PMID- 10201001
TI  - A laboratory model of toxin-induced hemolytic uremic syndrome.
AB  - BACKGROUND: Verocytotoxin-producing (Shiga-like toxin-producing) Escherichia coli
      infection is the principal cause of hemolytic uremic syndrome (HUS). The
      pathogenesis is unclear, and there is a need for animal models. These are impeded
      by the different distribution of verocytotoxin receptors between species. We have
      circumvented this restriction using ricin, which gains entry into cells via
      various galactose receptors. Like verocytotoxin, ricin specifically cleaves a
      single adenine from ribosomal RNA. METHODS: Rats were given ricin at a dose of
      6.7 micrograms/100 g body wt, with or without lipopolysaccharide at 10
      micrograms/100 g body wt. Lipopolysaccharide alone or saline were used as
      controls. Changes in glomerular filtration rate, hematological parameters,
      histology, and plasma cytokine concentrations were measured. RESULTS: Extensive
      glomerular thrombosis, pyknotic nuclei, and an infiltration of ED1-positive cells
      into glomeruli were observed eight hours after an injection of ricin. Other
      vascular beds were unaffected. Histologic changes were preceded by oliguric renal
      failure, hemolysis, and thrombocytopenia. Ricin produced a rise in plasma
      concentrations of monocyte chemotactic protein-1, > tumor necrosis factor-alpha,
      > interleukin-1 beta, > interleukin-6. Interferon-gamma showed a small increase
      at the end of the experiment. CONCLUSIONS: Ricin induces glomerular thrombotic
      microangiopathy, closely resembling that which occurs in verocytotoxin-producing
      E. coli-induced HUS. As in HUS, high concentrations of proinflammatory cytokines
      are present, which are probably a result of cytokine superinduction by the toxin.

PMID- 10201002
TI  - Expression of PRAD1/cyclin D1, retinoblastoma gene products, and Ki67 in
      parathyroid hyperplasia caused by chronic renal failure versus primary adenoma.
AB  - BACKGROUND: In primary hyperparathyroidism, certain genetic abnormalities
      responsible for parathyroid tumorigenesis are proposed, and it has been reported
      that the overexpression of PRAD1/cyclin D1 induced by a DNA rearrangement of the
      parathyroid hormone (PTH) gene is one of the genetic disorders in a number of
      primary parathyroid adenomas. However, in secondary hyperparathyroidism caused by
      uremia, the mechanism of monoclonal proliferation in nodular parathyroid
      hyperplasia is not well understood. To elucidate the mechanism, we examined the
      expression of PRAD1/cyclin D1, retinoblastoma gene products, and Ki67 in primary
      adenoma and secondary hyperplasia. METHODS: In adenomas (N = 15) and associated
      glands (N = 7) with normal histology obtained from patients with primary
      hyperparathyroidism and in diffuse (N = 14), multinodular (N = 58), and single
      nodular (N = 28) glands from patients who underwent parathyroidectomy for renal
      hyperparathyroidism, the expression of these cell cycle regulators was evaluated
      by immunohistochemical technique. A labeling index was used to define the
      proportion of cells with positive nuclear staining by each antibody. RESULTS: In
      6 out of 15 (40%) primary adenomas, PRAD1/cyclin D1 was overexpressed (a labeling
      index of more than 500), possibly because of the PTH gene rearrangement, but not
      in secondary hyperplasia, including single nodular glands. Compared with diffuse
      hyperplasia, nodular hyperplasia showed a significantly higher expression of
      PRAD1/cyclin D1 (P < 0.05), retinoblastoma gene products (P < 0.05), and Ki67 (P
      < 0.05). However, no statistically significant correlation between the expression
      of PRAD1/cyclin D1 and that of Ki67 was observed in both primary adenoma and
      secondary hyperplasia. CONCLUSIONS: These results suggest that in secondary
      hyperplasia caused by uremia, at least remarkable overexpression of PRAD1/cyclin
      D1 induced by PTH gene rearrangement may be not the major genetic abnormality
      responsible for tumorigenesis. Heterogenous genetic changes seem to contribute to
      monoclonal proliferation of parathyroid cells induced by the expression of
      PRAD1/cyclin D1 or by some other mechanism independent of the amplification of
      the proto-oncogene.

PMID- 10201003
TI  - Distribution of postsynaptic density proteins in rat kidney: relationship to
      neuronal nitric oxide synthase.
AB  - BACKGROUND: Neuronal nitric oxide synthase (nNOS) is expressed in skeletal muscle
      beneath the sarcolemma associated with dystrophin complex. In brain, nNOS is
      anchored to synaptic membranes by specific postsynaptic density proteins (PSD)-95
      and PSD-93. We have investigated the cellular and subcellular localization of
      these PSD proteins in the kidney and their relationship to nNOS and the cell
      membrane. METHODS: Kidneys from male Sprague-Dawley rats were processed for light
      and electron microscopic immunohistochemistry with polyclonal antibodies against
      PSD and nNOS proteins. RESULTS: Western blot analysis of rat kidney revealed a
      specific band for PSD-93 at the molecular weight of 103 kDa. Immunostaining for
      PSD-93 was located in the thick ascending limb of the loop of Henle, macula densa
      cells, distal convoluted tubules, cortical collecting ducts, outer and inner
      medullary collecting duct, glomerular epithelium, and Bowman's capsule. A pre
      embedding electron microscopic immunoperoxidase procedure localized PSD-93 to the
      basolateral membrane of these tubular cells. Using different sized immunogold
      particles, a portion of nNOS in the macula densa colocalized with PSD-93 adjacent
      to cytoplasmic vesicles and the basolateral membrane. In contrast, PSD-95 protein
      was detected only weakly in the cortex by Western blot. Immunostaining for PSD-95
      was located only faintly in the apical membrane of the thick ascending limb,
      macula densa, distal convoluted tubule and cortical collecting duct cells.
      CONCLUSION: PSD-93 is the predominant PSD expressed in the rat kidney. It is
      located primarily in the basolateral membranes of distal nephron and colocalizes
      with a pool of nNOS in cytoplasmic vesicles and basolateral membranes of macula
      densa cells.

PMID- 10201005
TI  - Expression and distribution of adenosine diphosphate-ribosylation factors in the
      rat kidney.
AB  - BACKGROUND: Adenosine diphosphate (ADP)-ribosylation factors (ARFs) are small
      guanosine triphosphatases involved in membrane traffic regulation. Aiming to
      explore the possible involvement of ARF1 and ARF6 in the reabsorptive properties
      of the nephron, we evaluated their distribution along the different renal
      epithelial segments. METHODS: ARFs were detected by immunofluorescence and
      immunogold cytochemistry on renal sections, using specific anti-ARF antibodies.
      RESULTS: ARF1 was detected in proximal and distal tubules, thick ascending limbs
      of Henle's loops, and cortical and medullary collecting ducts. By
      immunofluorescence, labeling was mostly localized to the cell cytoplasm,
      particularly in Golgi areas. By electron microscopy, the Golgi apparatus and the
      endosomal compartment of proximal and distal tubular cells were labeled. ARF6
      immunofluorescence was observed in brush border membranes and the cytoplasm of
      proximal convoluted tubular cells, whereas it was restricted to the apical border
      of proximal straight tubules. ARF6 immunogold labeling was detected over
      microvilli and endocytic compartments of proximal tubular cells. CONCLUSIONS:
      This study demonstrates the following: (a) the heterogeneous distributions of
      ARF1 and ARF6 along the nephron, (b) the existence of cytosolic and membrane
      bound forms for both ARFs, and (c) their association with microvilli and
      endocytic compartments, suggesting an active participation in renal reabsorption.

PMID- 10201004
TI  - Immunomodulatory effects of interferon-gamma on autoreactive nephritogenic T-cell
      clones.
AB  - BACKGROUND: We examined the immunomodulatory effects of interferon-gamma (IFN
      gamma) on renal-derived CD4+ alpha/beta + T cells, called mouse renal (MR) cells,
      isolated from animals with murine chronic graft-versus-host disease, a model of
      autoimmune glomerulonephritis. MR T cells express a Th2 cytokine profile,
      although IFN-gamma expression is also detected in a subset of clones that
      adoptively transfers renal disease to naive recipients. In view of disparate
      patterns of IFN-gamma expression, we evaluated the effects of exogenous IFN-gamma
      on nephritogenic (MR1.3) and nonnephritogenic (MR1.6) clonal activity. METHODS:
      These studies examined IFN-gamma-mediated effects on clonal proliferation,
      cytokine production, nephritogenic potential, and IFN-gamma receptor expression.
      RESULTS: IFN-gamma mediated dose-dependent inhibition of MR1.3 and MR1.6
      proliferation. This cytostatic effect was not mediated by inhibiting cytokine
      genes, as expression of interleukin (IL)-4, IL-10, IL-13, and IFN-gamma after IFN
      gamma treatment was not markedly altered in either clone, although baseline IL-13
      expression was enhanced in MR1.6. IFN-gamma markedly altered the functional
      phenotype of MR1.6, as pretreated recipients developed severe mononuclear cell
      infiltrates and tubular damage following adoptive transfer of MR1.6. Neutralizing
      anti-IFN-gamma antibodies did not inhibit MR1.3 nephritogenicity, but did block
      MR1.6-induced disease in IFN-gamma-treated mice. Although both clones
      constitutively expressed the IFN-gamma receptor beta chain, IFN-gamma exposure
      decreased its expression in MR1.3 cells, but did not markedly change its
      expression in MR1.6 cells. CONCLUSION: These studies describe an unusual
      permissive role for IFN-gamma in modulating nephritogenic Th2 activity in vivo,
      which facilitates the initiation of cell-mediated autoimmune renal injury.
      Apparent differential effects of IFN-gamma on distinct T-cell clones may be
      mediated in part by alterations in cytokine receptor expression.

PMID- 10201006
TI  - Hypertonicity-induced accumulation of organic osmolytes in papillary interstitial
      cells.
AB  - BACKGROUND: Medullary cells of the concentrating kidney are exposed to high
      extracellular solute concentrations. It is well established that epithelial cells
      in this kidney region adapt osmotically to hypertonic stress by accumulating
      organic osmolytes. Little is known, however, of the adaptive mechanisms of a
      further medullary cell type, the papillary interstitial cell [renal papillary
      fibroblast (RPF)]. We therefore compared the responses of primary cultures of
      RPFs and papillary collecting duct (PCD) cells exposed to hypertonic medium.
      METHODS: In RPFs and PCD cells, organic osmolytes were determined by high
      performance liquid chromatography; mRNA expression for organic osmolyte
      transporters [Na+/Cl(-)-dependent betaine transporter (BGT), Na(+)-dependent myo
      inositol transporter (SMIT)], and the sorbitol synthetic and degrading enzymes
      [aldose reductase (AR) and sorbitol dehydrogenase (SDH), respectively] was
      determined by Northern blot analysis. RESULTS: Exposure to hypertonic medium (600
      mOsm/kg by NaCl addition) caused intracellular contents of
      glycerophosphorylcholine, betaine, myo-inositol, and sorbitol, but not free amino
      acids, to increase significantly in both RPFs and PCD cells. The rise in
      intracellular contents of these organic osmolytes was accompanied by enhanced
      expression of mRNAs coding for BGT, SMIT, and AR in both RPFs and PCD cells. SDH
      mRNA abundance, however, was unchanged. Nonradioactive in situ hybridization
      studies on sections from formalin-fixed and paraffin-embedded, normally
      concentrating kidneys showed strong expression of BGT, SMIT, and AR mRNAs in
      interstitial and collecting duct cells of the papilla, whereas expression of SDH
      mRNA was much weaker in both cell types. CONCLUSIONS: These results suggest that
      both RPFs and PCD cells use similar strategies to adapt osmotically to the high
      interstitial NaCl concentrations characteristic for the inner medulla and papilla
      of the concentrating kidney.

PMID- 10201007
TI  - Cell type-specific acquired protection from crystal adherence by renal tubule
      cells in culture.
AB  - BACKGROUND: Adherence of crystals to the surface of renal tubule epithelial cells
      is considered an important step in the development of nephrolithiasis.
      Previously, we demonstrated that functional monolayers formed by the renal tubule
      cell line, Madin-Darby canine kidney (MDCK), acquire protection against the
      adherence of calcium oxalate monohydrate crystals. We now examined whether this
      property is cell type specific. The susceptibility of the cells to crystal
      binding was further studied under different culture conditions. METHODS: Cell
      type specificity and the influence of the growth substrate was tested by
      comparing calcium oxalate monohydrate crystal binding to LLC-PK1 cells and to two
      MDCK strains cultured on either permeable or impermeable supports. These cell
      lines are representative for the renal proximal tubule (LLC-PK1) and distal
      tubule/collecting duct (MDCK) segments of the nephron, in which crystals are
      expected to be absent and present, respectively. RESULTS: Whereas relatively
      large amounts of crystals adhered to subconfluent MDCK cultures, the level of
      crystal binding to confluent monolayers was reduced for both MDCK strains. On
      permeable supports, MDCK cells not only obtained a higher level of morphological
      differentiation, but also acquired a higher degree of protection than on
      impermeable surfaces. Crystals avidly adhered to LLC-PK1 cells, irrespective of
      their developmental stage or growth substrate used. CONCLUSIONS: These results
      show that the prevention of crystal binding is cell type specific and expressed
      only by differentiated MDCK cells. The anti-adherence properties acquired by MDCK
      cells may mirror a specific functional characteristic of its in situ equivalent,
      the renal distal tubule/collecting ducts.

PMID- 10201008
TI  - Phosphate depletion in the rat: effect of bisphosphonates and the calcemic
      response to PTH.
AB  - BACKGROUND: The removal of phosphate from the diet of the growing rat rapidly
      produces hypercalcemia, hypophosphatemia, hypercalciuria, and hypophosphaturia.
      Increased calcium efflux from bone has been shown to be the important cause of
      the hypercalcemia and hypercalciuria. It has been proposed that the increased
      calcium efflux from bone is osteoclast mediated. Because bisphosphonates have
      been shown to inhibit osteoclast-mediated bone resorption, this study was
      performed to determine whether bisphosphonate-induced inhibition of osteoclast
      function changed the biochemical and bone effects induced by phosphate depletion.
      METHODS: Four groups of pair-fed rats were studied: (a) low-phosphate diet (LPD;
      phosphate less than 0.05%), (b) LPD plus the administration of the bisphosphonate
      Pamidronate (APD; LPD + APD), (c) normal diet (ND, 0.6% phosphate), and (d) ND +
      APD. All diets contained 0.6% calcium. A high dose of APD was administered
      subcutaneously (0.8 mg/kg) two days before the start of the study diet and on
      days 2, 6, and 9 during the 11 days of the study diet. On day 10, a 24-hour urine
      was collected, and on day 11, rats were either sacrificed or received an
      additional APD dose before a 48-hour parathyroid hormone (PTH) infusion (0.066
      microgram/100 g/hr) via a subcutaneously implanted miniosmotic pump. RESULTS:
      Serum and urinary calcium were greater in the LPD and LPD + APD groups than in
      the ND and ND + APD groups [serum, 11.12 +/- 0.34 and 11.57 +/- 0.45 vs. 9.49 +/-
      0.17 and 9.48 +/- 0.15 mg/dl (mean +/- SE), P < 0.05; and urine, 8.78 +/- 2.74
      and 16.30 +/- 4.68 vs. 0.32 +/- 0.09 and 0.67 +/- 0.28 mg/24 hr, P < 0.05]. Serum
      PTH and serum and urinary phosphorus were less in the LPD and LPD + APD than in
      the ND and ND + APD groups (P < 0.05). The calcemic response to PTH was less (P <
      0.05) in the LPD and LPD + APD groups than in the ND group and was less (P =
      0.05) in the LPD + APD than in the ND + APD group. Bone histology showed that
      phosphate depletion increased the osteoblast and osteoclast surface, and
      treatment with APD reduced the osteoblast surface (LPD vs. LPD + APD, 38 +/- 4
      vs. 4 +/- 2%, P < 0.05, and ND vs. ND + APD, 20 +/- 2 vs. 5 +/- 2%, P < 0.05) and
      markedly altered osteoclast morphology by inducing cytoplasmic vacuoles.
      CONCLUSIONS: (a) Phosphate depletion induced hypercalcemia and hypercalciuria
      that were not reduced by APD administration. (b) The calcemic response to PTH was
      reduced in phosphate-depleted rats and was unaffected by APD administration in
      normal and phosphate-depleted rats, and (c) APD administration markedly changed
      bone histology without affecting the biochemical changes induced by phosphate
      depletion.

PMID- 10201009
TI  - Cl- channels in basolateral TAL membranes. XIV. Kinetic properties of a
      basolateral MTAL Cl- channel.
AB  - BACKGROUND: This article reports studies on the kinetics of chloride (Cl-)
      conductance in Cl- channels fused into bilayers from basolaterally enriched
      vesicles from rabbit outer medulla. A considerable body of evidence indicates
      that these channels represent rbClC-Ka, a 77 kDa kidney-specific protein of the
      ClC family of Cl- channels. rbClC-Ka, a candidate channel for mediating net Cl-
      absorption in the medullary thick ascending limb (MTAL), has been cloned from
      rabbit outer medulla and localized by immunofluorescence to basolateral membranes
      of the MTAL. Thus, this is the first account, to our knowledge, of the kinetics
      of ion permeation through a renal Cl- channel mediating net basolateral Cl-
      absorption in the thick ascending limb of Henle (TALH), and this channel may
      represent rbClC-Ka. METHODS: The electrophysiological properties of these
      channels were studied by fusing basolaterally enriched MTAL vesicles into planar
      bilayer membranes. RESULTS: Cl- conductance through these channels was
      concentration dependent and saturable. The relationship between gCl (pS) and
      symmetrical aqueous Cl- concentrations could be expressed in terms of the
      Michaelis equation with a limiting conductance (GClmax, pS) of 114 pS at
      infinitely high aqueous Cl- concentrations and a K1/2 of 163 mM Cl-. A log-log
      plot of the conductance-Cl- concentration relations, in the nonsaturating Cl-
      concentration range, had a slope of 0.91, that is, virtually unity. The
      relatively impermeant anion I- produced a voltage-dependent conductance blockade
      that could be overcome at high electric field strengths. CONCLUSIONS: The
      experimental data described earlier here fulfill the traditional criteria for a
      first-order process with a single Cl- ion occupying these channels at a given
      time. Although the channels may contain multiple ion binding sites, the latter
      function, in integral kinetic terms, as a single rate-limiting locus.

PMID- 10201010
TI  - Lp(a) and LDL induce apoptosis in human endothelial cells and in rabbit aorta:
      role of oxidative stress.
AB  - BACKGROUND: Atherogenic lipoproteins cause injury to the vascular wall in the
      early phase of atherogenesis. We assessed the effects of native (nLDL) and
      oxidized (oxLDL) low-density lipoprotein (LDL) and lipoprotein (a) [Lp(a)] on O2-
      formation and cell death in cultured human umbilical vein endothelial cells
      (HUVECs) and rabbit aorta (RA). METHODS AND RESULTS: O2- formation of HUVECs and
      RA segments was not influenced by nLDL, but was dose dependently increased by
      oxLDL and was moderately increased by nLp(a). oxLp(a) was the most potent
      stimulus for O2- formation, increasing it in HUVECs by 356% at 5 micrograms/ml
      and in RA by 294% at 100 micrograms/ml. Apoptosis was detected by DNA
      fragmentation and Annexin assay in HUVECs and by TUNEL staining in RA. Incubation
      of HUVECs and RA with oxLDL, but not nLDL, dose and time dependently induced
      apoptosis with only a minimal effect on necrosis. nLp(a) elicited a small but
      significant effect on apoptosis, whereas oxLp(a) induced apoptosis more potently
      than oxLDL in HUVECs and RA and caused necrotic cell death in HUVECs. Induction
      of apoptosis by oxLDL and oxLp(a) in RA was enhanced by the superoxide dismutase
      (SOD) inhibitor, diethyl-dithio-carbamate, and was blunted by SOD and catalase in
      HUVECs and RA, suggesting that O2- formation was involved. The concentration of
      lysophosphatidylcholine, a lipoprotein oxidation product and stimulus for O2-
      formation, was significantly enhanced by factor 5 in oxLDL and by factor 7 in
      oxLp(a) compared with native lipoproteins. CONCLUSION: Atherogenic lipoproteins
      stimulate O2- formation and induction of apoptosis in HUVECs and RA, and may
      thereby influence the pathogenesis of atherosclerosis.

PMID- 10201011
TI  - Large juxtamedullary glomeruli and afferent arterioles in healthy primates.
AB  - BACKGROUND: Differences in the functional demands of superficial and
      juxtaglomerular nephrons could result in differences in glomerular size between
      these two types of nephrons. This concept is based on animal models in which the
      juxtamedullary glomeruli and afferent arteriole diameters are indeed larger than
      those in the outer cortical zones. However, this difference was not confirmed in
      human necropsy studies. To obtain further information in living primates, we have
      made unbiased estimates of glomerular and afferent arteriole dimensions in three
      cortical zones (superficial, midcortical, and juxtamedullary) in young, adult,
      normotensive monkeys. METHODS: In each animal (N = 6), the right kidney was
      perfusion fixed and prepared for unbiased stereological estimation of glomerular
      number and size. The left kidney vasculature was fixed while relaxed and at a
      known intravascular pressure. Thereafter, afferent arteriolar dimensions were
      estimated using light and confocal microscopy. RESULTS: The mean glomerular
      volume was variable between animals (coefficient of variation, 23%) and was
      largest in the juxtamedullary zone. Afferent arteriolar lumen diameter varied
      little between animals (coefficient of variation, 3%), but was also the largest
      in the juxtamedullary zone. No sclerotic glomeruli were found in any of the
      animals. CONCLUSION: The findings show that in normal primates, as previously
      shown in other animals, juxtamedullary glomeruli and afferent arteriolar
      diameters are larger compared with those in the outer cortical zones.

PMID- 10201012
TI  - Prevalence and determinants of hyperhomocysteinemia in hemodialysis and
      peritoneal dialysis.
AB  - BACKGROUND: Hyperhomocysteinemia is an independent risk factor for
      atherosclerotic complications in patients with end-stage renal disease, although
      the mechanisms remain unclear. The major determinants of plasma homocysteine
      concentration are usually folate, vitamin B12, pyridoxal 5'-phosphate (vitamin
      B6), and glomerular filtration rate. METHODS: We measured factors, including
      plasma folate, vitamin B12, vitamin B6, creatinine, as well as the dose and
      duration of dialysis, that might affect plasma homocysteine concentrations in 130
      patients on hemodialysis (HD) and compared these observations with those in 46
      patients on peritoneal dialysis (PD). Independent determinants of total
      homocysteine were identified using a multiple logistical regression analysis.
      RESULTS: Total homocysteine values averaged 29.8 mumol/liter in HD patients,
      significantly higher than the mean value of 19.9 mumol/liter observed in patients
      on PD (P < 0.001). The prevalence of hyperhomocysteinemia was 90.8% among HD
      patients, significantly higher than the prevalence of 67.4% among PD patients.
      Folate values in HD patients averaged 45.5 nmol/liter and were significantly
      lower than in PD patients (104.2 nmol/liter, P < 0.001). For patients on HD, the
      only determinant of total homocysteine concentration was plasma folate (r = 
      0.31, P < 0.001). In contrast, for PD patients, total homocysteine did not
      correlate with plasma folate, vitamin B12, or vitamin B6. CONCLUSIONS:
      Hyperhomocysteinemia is more prevalent and intense in HD patients compared with
      those on PD. The homocysteine response may become refractory to excess folate
      supplementation in PD patients.

PMID- 10201013
TI  - Mortality and technique failure in patients starting chronic peritoneal dialysis:
      results of The Netherlands Cooperative Study on the Adequacy of Dialysis. NECOSAD
      Study Group.
AB  - BACKGROUND: Recent studies have shown an association between small solute
      clearance and patient survival. Thus far, little attention has been paid to the
      potential effects of fluid overload. The aim of this study was to determine the
      relative importance of baseline patient and treatment characteristics to
      mortality and technique failure in patients starting peritoneal dialysis.
      METHODS: One hundred and eighteen consecutive new patients were included in this
      prospective multicenter cohort study. Cox proportional hazards regression was
      used to predict mortality and technique failure. RESULTS: There were 33 deaths
      and 44 technique failures. The two-year patient survival was 77%, and the two
      year technique survival was 64%. Age, systolic blood pressure, and the absolute
      quantity of small solutes removed at baseline were independent predictors of
      mortality. A one-year increase in age was associated with a relative risk (RR) of
      death of 1.05 (95% CI, 1.01 to 1.09) and a 10 mm Hg rise in systolic blood
      pressure, with a RR of 1.42 (95% CI, 1.17 to 1.73). The removal of 1
      mmol/week/1.73 m2 of urinary and dialysate creatinine was associated with a RR of
      death of 0.95 (95% CI, 0.92 to 0.98) and 0.93 (95% CI, 0.89 to 0.98). The removal
      of urea had a similar association with the RR of death. Predictors for technique
      failure were urine volume, peritoneal ultrafiltration, and systolic blood
      pressure. CONCLUSIONS: Dialysate solute removal was an independent predictor of
      mortality. The association between systolic blood pressure and mortality shows
      that the maintenance of fluid balance and the removal of small solutes deserve
      equal attention.

PMID- 10201014
TI  - Vesicoureteral reflux in male and female neonates as detected by voiding
      ultrasonography.
AB  - BACKGROUND: Vesicoureteral reflux (VUR) is assumed to be congenital, and its
      early diagnosis is desired in order to prevent acquired renal damage. However,
      the incidence of VUR in neonates remains to be revealed. METHODS: Two thousand
      newborn babies (1048 boys and 952 girls) underwent voiding ultrasonography (an
      ultrasound examination of urinary tract during provoked voiding). Those who
      showed transient renal pelvic dilation during voiding, who had small kidneys, or
      who subsequently developed urinary infection underwent voiding
      cystourethrography. RESULTS: Transient renal pelvic dilation was observed in 16
      babies (0.8%), including one boy with small kidneys. Among the rest of the
      babies, one boy had a small kidney, and nine babies subsequently developed
      urinary infection. Voiding cystourethrography revealed VUR in 24 ureters of 16
      children (11 boys and 5 girls). Dimercaptosuccinate renoscintigraphy confirmed
      small kidneys, with generally reduced tracer uptake in a total of three boys, all
      having VUR. Voiding ultrasonography detected transient renal pelvic dilation in
      17 (71%) of the 24 kidneys with VUR and, strikingly, 16 of the 17 (94%) kidneys
      with high-grade VUR (grade III or more). CONCLUSION: This study effectively
      detected VUR in 0.8% of the neonates (mostly of high grades and predominantly in
      males) and voiding ultrasonography showed a decided usefulness for the detection
      of VUR. The male preponderance of VUR in neonates was considered to be due to the
      occurrence of congenitally small kidneys, with reflux found exclusively in males
      and easier ultrasound detection of VUR in male neonates because the majority of
      diagnoses are reported to be high grades of VUR.

PMID- 10201015
TI  - Up-regulation of Duffy antigen receptor expression in children with renal
      disease.
AB  - BACKGROUND: The Duffy antigen chemokine receptor (DARC) is a promiscuous
      chemokine receptor that binds chemokines from the C-X-C and C-C families. DARC
      was initially described on red blood cells, but subsequent studies have
      demonstrated DARC protein expression on renal endothelial and epithelial cells,
      even in Duffy-negative individuals whose red cells lack DARC. Because
      approximately 68% of African Americans lack the Duffy/DARC on their red cells, we
      carried out experiments to identify the specific renal cells expressing DARC
      protein and mRNA in African American children and to define whether DARC
      expression was altered in renal inflammatory processes. METHODS:
      Immunohistochemistry and in situ hybridization studies were done in 28 renal
      sections from children with each of the following diagnoses: HIV nephropathy
      (HIVAN), HIV-associated hemolytic uremic syndrome (HIV-HUS), HIV infection
      without renal disease, HIV-negative children without renal disease, and
      Argentinean children with classic HUS. RESULTS: The predominant localization of
      DARC mRNA and protein was found in endothelial cells underlying postcapillary
      renal venules in all patients studied. However, DARC mRNA and protein were
      significantly up-regulated in peritubular and glomerular capillaries, collecting
      duct epithelial cells, and interstitial inflammatory cells in children with
      HIVAN, HIV-HUS, and classic HUS. CONCLUSION: These findings support the notion
      that the renal DARC is linked to the inflammatory cascade and that African
      American children may be at risk of accumulating chemokines in renal tissues.

PMID- 10201016
TI  - Measurement of the delivery of dialysis in acute renal failure.
AB  - BACKGROUND: Recent studies in patients with acute renal failure (ARF) have shown
      a relationship between the delivered dose of dialysis and patient survival.
      However, there is currently no consensus on the appropriate method to measure the
      dose of dialysis in ARF patients. In this study, the dose of dialysis was
      measured by blood- and dialysate-based kinetic methods in a group of ARF patients
      who required intermittent hemodialysis. METHODS: Treatments were performed using
      a Fresenius 2008E volumetric hemodialysis machine with the ability to
      fractionally collect the spent dialysate. Single-, double-pool, and equilibrated
      Kt/V were determined from the pre-, immediate post-, and 30-minute post-blood
      urea nitrogen (BUN) measurements. The solute reduction index was determined from
      the collected dialysate, as well as the single- and double-pool Kt/V. RESULTS:
      Forty-six treatments in 28 consecutive patients were analyzed. The mean
      prescribed Kt/V (1.11 +/- 0.32) was significantly greater than the delivered dose
      estimated by single-pool (0.96 +/- 0.33), equilibrated (0.84 +/- 0.28), and
      double-pool (0.84 +/- 0.30) Kt/V (compared with prescribed, each P < 0.001).
      There was no statistical difference between the equilibrated and double-pool Kt/V
      (P = NS). The solute removal index, as determined from the dialysate,
      corresponded to a Kt/V of 0.56 +/- 0.27 and was significantly lower than the
      single-pool and double-pool Kt/V (each P < 0.001). CONCLUSION: Blood-based
      kinetics used to estimate the dose of dialysis in ARF patients on intermittent
      hemodialysis provide internally consistent results. However, when compared with
      dialysate-side kinetics, blood-based kinetics substantially overestimated the
      amount of solute (urea) removal.

PMID- 10201017
TI  - Kidney transplanted children come of age.
AB  - BACKGROUND: The aim of renal replacement therapy in children is to restore their
      potential for normal growth and development in order to reach mature adulthood.
      Because pediatric kidney transplantation started in the late 1960s, it is now
      possible to document the progress and outcome of these patients from
      transplantation in childhood to survival into adulthood. METHODS: In this single
      center study, all 150 children born before December 1977 and having received a
      kidney transplant between 1970 and 1993 were selected for long-term follow-up.
      The mean age at transplantation was 12.1 years (range 3.2 to 16.7), and the mean
      follow-up was 13.1 years (range 2.0 to 25.0). In December 1995, 124 grown-up
      patients with a mean age of 25.4 years (range 18.4 to 40.3) were alive, 89 with a
      functioning graft. Fifty had the first graft functioning longer than 10 years.
      The fate of all patients was traced, and those living were analyzed in regard to
      their somatic and socioeconomic states. RESULTS: The actuarial 25-year survival
      rate for the patients was 81%, and for the first graft it was 31%. The best graft
      survival rates were observed after living related donation, preemptive
      transplantation, and immunosuppression with cyclosporine. The latter benefit,
      however, vanished after eight years. The mean creatinine clearance declined over
      the years from 76 to 45 ml/min/1.73 m2, and the incidence of hypertension
      increased to more than 80% of the patients. Malignancies occurred in 2.6%. Final
      height was stunted in 44% of noncystinotic patients, whereas all patients with
      cystinosis were extremely growth retarded. Twenty-seven percent suffered from
      additional disabilities. A majority of adult patients were rehabilitated in
      regard to education and socioeconomic status, and 14% were unemployed.
      CONCLUSIONS: The results indicate that renal transplantation in children leads to
      a high degree of rehabilitation in adulthood. The life of a kidney transplant,
      however, is limited, which points out the need for more specific
      immunosuppression with fewer side-effects in order to reach the goal of lifelong
      graft function.

PMID- 10201019
TI  - Supervised atenolol therapy in the management of hemodialysis hypertension.
AB  - BACKGROUND: Uncontrolled hypertension continues to be a common problem,
      particularly in noncompliant hemodialysis patients. Atenolol, a water soluble
      beta-blocker has a prolonged half-life in renal failure and may serve as a useful
      antihypertensive agent in these patients. METHODS: Hypertension was diagnosed by
      ambulatory blood pressure monitoring for 44 hours during an interdialytic
      interval in eight chronic hemodialysis patients receiving no antihypertensive
      therapy. An average daytime blood pressure greater than 140/90 mm Hg or an
      average nighttime blood pressure greater than 120/80 mm Hg was used to define
      uncontrolled hypertension. Patients were then administered atenolol (25 mg)
      following hemodialysis three times a week. The efficacy of therapy was judged by
      ambulatory blood pressure monitoring three weeks after instituting atenolol
      therapy. Blood pressure loads above the threshold blood pressures during the day
      or night were also calculated and compared before and after three weeks of
      atenolol therapy. RESULTS: The mean 44-hour ambulatory blood pressure (ABP) fell
      from 144 +/- 14/80 +/- 7 mm Hg to 127 +/- 13/69 +/- 10 mm Hg (P < 0.001). The
      heart rate fell from 85 +/- 11 to 70 +/- 11 beats per minute. The systolic and
      diastolic blood pressure load was reduced from 71 +/- 25% and 30 +/- 24% to 35 +/
      26% and 11 +/- 17%, respectively (P < 0.001). There was a persistent
      antihypertensive effect over 44 hours. The blood pressure reduction was achieved
      without any increase in intradialytic symptomatic or asymptomatic hypotensive
      episodes, reduction in delivered dialysis, or statistically significant changes
      in serum potassium or glucose. CONCLUSIONS: A supervised administration of
      atenolol following hemodialysis effectively and safely controls hypertension in
      chronic hemodialysis patients. This therapy can be particularly valuable for
      noncompliant hemodialysis patients.

PMID- 10201018
TI  - Effects of FK506 in rat and human resistance arteries.
AB  - BACKGROUND: FK506 is widely used in organ transplantation and causes
      hypertension. However, little is known about the impact of the drug on the
      cardiovascular system. METHODS: We therefore investigated the effect of FK506 on
      resistance artery and blood pressure responsiveness to vasoconstrictors and
      vasodilators. Studies were conducted in vitro using human and murine resistance
      artery, ex vivo in resistance artery isolated from rats treated with FK506 (6
      mg/kg/day), and in vivo in conscious, treated animals. RESULTS: In vitro exposure
      (24 hr) of human and rat resistance artery to FK506 (1000 ng/ml) increased the
      sensitivity to norepinephrine (NE) and impaired the response to acetylcholine
      (Ach) and sodium nitroprusside (SNp). In contrast, arteries isolated from rats
      given FK506 for eight days showed a reduced sensitivity to NE (P < 0.05) and a
      normal endothelium-dependent relaxation. Their incubation with L-arginine caused
      a significant reduction in Ach sensitivity in the FK506 group (P < 0.05) but not
      in controls, suggesting enhancement of nitric oxide production by the drug. The
      sensitivity to SNp was reduced, as in the in vitro experiments (P < 0.05). Rats
      given FK506 for eight days presented blood pressure similar to that in controls
      but also presented signs of a compensatory response to excess vasodilation:
      tachycardia (P < 0.01), reduced blood pressure sensitivity to NE and Ach, blunted
      heart rate response to both agonists, and exaggerated hypotension at high doses
      of Ach. After 21 days of treatment, blood pressure remained similar to that in
      controls, but resistance artery showed further functional deterioration, with
      significant impairment of the maximum responses to Ach and to SNp. CONCLUSION:
      FK506 presents significant vascular toxicity affecting mainly smooth muscle
      relaxation and alters vascular hemodynamics. The data suggest that similar
      cardiovascular changes may occur in transplant patients and represent the
      forerunner of hypertension often seen with more prolonged use of the drug.

PMID- 10201020
TI  - Apolipoprotein B-containing lipoproteins in renal failure: the relation to mode
      of dialysis.
AB  - BACKGROUND: The aim of this study was to establish whether there is a
      differential effect of mode of dialysis, hemodialysis (HD), or continuous
      ambulatory peritoneal dialysis (CAPD) on the dyslipidemia of renal failure.
      METHODS: The lipoprotein profile was determined in 61 non-diabetic patients on
      chronic HD (N = 30) and CAPD treatment (N = 31), and in a control group of 27
      healthy subjects. The analysis included the measurement of individual
      apolipoprotein (apo) A- and apo B-containing lipoproteins (LPs) separated by
      sequential immunoaffinity chromatography. Apo A-containing lipoproteins include
      lipoprotein A-I with apo A-I and lipoprotein A-I:A-II with apo A-I and apo A-II
      as the main protein constituents, whereas apo B-containing lipoproteins comprise
      simple cholesterol-rich lipoprotein B (LP-B), with apo B as the only protein
      moiety and complex triglyceride (TG)-rich lipoprotein B complex (LP-Bc) particles
      with apo B, apo A-II, apo C, and/or apo E as the protein constituents. RESULTS:
      CAPD patients had significantly higher concentrations of total cholesterol (6.8
      vs. 5.1 mmol/liter), low-density lipoprotein (LDL) cholesterol (4.6 vs. 3.2
      mmol/liter), TG (2.3 vs. 1.5 mmol/liter), apo B (155.3 vs. 105.7 mg/dl), LP-B
      (136.0 vs. 91.9 mg/dl), and LP-Bc (19.3 vs. 13.8 mg/dl) than HD patients. Both HD
      and CAPD patients had significantly higher TG, VLDL cholesterol, apo C-III, and
      apo E and significantly lower high-density lipoprotein cholesterol, apo A-II, and
      lipoprotein A-I:A-II levels than control subjects. The distribution of apo C-III
      in high-density lipoprotein and VLDL-LDL was altered in CAPD patients in
      comparison with control subjects. This suggests that the removal of TG-rich
      lipoproteins is less efficient in patients on CAPD. Normotriglyceridemic (NTG; TG
      < or = 1.7 mmol/liter, 150 mg/dl) CAPD patients had significantly higher levels
      of TC, LDL cholesterol, apo B, and LP-B than NTG-HD patients. There was little
      difference in the LP-Bc levels between NTG-CAPD, NTG-HD, and controls. Similarly,
      hypertriglyceridemic (HTG) CAPD patients had significantly higher TC, LDL
      cholesterol, apo B, and LP-B levels than HTG-HD patients. The LP-Bc levels were
      significantly increased in HTG-HD and HTG-CAPD patients compared with controls,
      but the slightly higher levels in the CAPD patients did not differ significantly
      from the HD group. CONCLUSION: CAPD and HD patients have a lipoprotein profile
      characteristic of renal failure. Patients on long-term CAPD have higher levels of
      cholesterol-rich apo B-containing lipoproteins unrelated to TG levels. Many
      patients on CAPD also have a substantial elevation of the plasma concentrations
      of TG-rich LPs. The clinical significance of increased levels of potentially
      atherogenic LP-B during CAPD remains to be investigated.

PMID- 10201021
TI  - CD40 expression on graft infiltrates and parenchymal CD154 (CD40L) induction in
      human chronic renal allograft rejection.
AB  - BACKGROUND: CD40-CD154 (CD40L) costimulatory signaling plays a pivotal role in
      the effector mechanisms of transplant graft rejection. In animal models, CD40
      CD154 blockade induces long-term graft acceptance concurrent with an absence of
      chronic rejection (CR) lesions. Given the critical importance of CD40-CD154
      interactions in the development of chronic transplant allograft rejection, the
      relevance of in situ CD40 and CD154 expression was assessed in human chronic
      renal allograft rejection. METHODS: The expression of CD40, CD154, CD68, and T
      cell receptor (TCR)alpha/beta was analyzed by immunohistochemistry. Serial
      cryostat sections of snap-frozen core renal allograft biopsies were obtained from
      30 renal transplant patients. Biopsy specimens received diagnoses of CR (N = 23)
      according to the Banff classification and were compared with controls (N = 7)
      consisting of stable allografts and normal kidney tissue. RESULTS: Striking CD40
      staining of graft cellular infiltrates (P = 0.016) was observed in renal
      allografts with CR compared with controls. The CD40+ cellular infiltrates in CR
      were predominantly TCR alpha/beta + T cells and some CD68+ macrophages. These
      findings were contrasted by the low-level CD40 expression detected in glomeruli
      and tubules of CR and controls. However, glomerular induction of CD154 was
      observed in CR allografts (P = 0.028) as compared with controls. CD154
      immunoreactivity was demonstrated on glomerular endothelial, epithelial, and
      mesangial cells. Moderate CD154 expression was detected on tubular epithelial
      cells, and only weak CD154 immunoreactivity was observed on the infiltrates in
      isolated CR cases. CONCLUSION: In human chronic renal allograft rejection, CD40
      is expressed on graft-infiltrating cells of the T cell and macrophage
      compartments. CD154 expression is induced on glomerular and tubular epithelial
      cells during CR, demonstrating another novel source of CD154 expression. The data
      substantiate the potential contributory role of an interaction between CD40+
      graft-destructive effector T cells and macrophages with CD154+ renal allograft
      parenchymal cells in the development of chronic renal allograft rejection.

PMID- 10201022
TI  - Sudden and cardiac death rates in hemodialysis patients.
AB  - BACKGROUND: Sudden and cardiac death (including death from congestive heart
      failure, myocardial infarction, and sudden death) are common occurrences in
      hemodialysis patients. The intermittent nature of hemodialysis may lead to an
      uneven distribution of sudden and cardiac death throughout the week. The purpose
      of this study was to assess the septadian rhythm of sudden and cardiac death in
      hemodialysis patients. METHODS: Data from the United States Renal Data System
      (USRDS) were obtained to examine the day of death for United States hemodialysis
      and peritoneal dialysis patients from 1977 through 1997. The days of death were
      also determined for patients in the Case Mix Adequacy Study of the USRDS.
      RESULTS: There was an even distribution of sudden and cardiac deaths for patients
      on peritoneal dialysis, and hemodialysis patients dying of noncardiac deaths also
      had an even distribution. For all hemodialysis patients, Monday and Tuesday were
      the most common days of sudden and cardiac death. For patients in the Case Mix
      Adequacy Study designated as Monday, Wednesday, and Friday dialysis patients,
      20.8% of sudden deaths occurred on Monday compared with the 14.3% expected (P =
      0.002). Similarly, 20.2% of cardiac deaths occurred on Monday compared with the
      14.3% expected (P = 0.0005). Similar trends were found on Tuesday for Tuesday,
      Thursday, and Saturday dialysis patients. CONCLUSIONS: The intermittent nature of
      hemodialysis may contribute to an increased sudden and cardiac death rate on
      Monday and Tuesday for patients enrolled in the USRDS.

PMID- 10201023
TI  - Influence of excess weight on mortality and hospital stay in 1346 hemodialysis
      patients.
AB  - BACKGROUND: Body mass index (BMI) at its extremes contributes to morbidity and
      mortality in the general population. Its influence on morbidity and mortality in
      patients on hemodialysis is not clearly defined. METHODS: The BMI in 1346
      patients attending limited-care hemodialysis units across the state of
      Mississippi was determined, and its relation to one-year mortality and hospital
      stay was assessed using the Cox proportional hazard model. RESULTS: Of these
      patients, 89% were black, and 11% were white. Thirty-eight percent of patients
      were overweight (BMI > 27.5), and 13% were underweight (BMI < 20). The highest
      (27.60 +/- 0.29, mean +/- SE) and the lowest (24.54 +/- 0.48) BMI were noted in
      black females and white males, respectively. BMI, race, hematocrit (Hct), and
      biochemical markers of better nutrition positively influenced the survival,
      whereas age, serum globulin, and diabetes had a negative influence. In a Cox
      multivariate analysis, BMI, age, diabetes, prealbumin, and creatinine, but not
      race, serum albumin, Hct, or serum globulin, retained significant influence on
      survival. Compared with the normal weight (BMI between 20 and 27.5), the one-year
      survival rate was significantly higher in the overweight patients and lower in
      the underweight patients. With a one-unit increase in BMI over 27.5, the relative
      risk for dying was reduced by 30% (P < 0.04), and with a one-unit decrease in BMI
      below 20, the relative risk was increased by 1.6-fold (P < 0.01). Furthermore,
      underweight patients had significantly lower levels of biochemical markers of
      nutrition and higher frequency and longer duration of hospital stay. CONCLUSION:
      Adequate dialysis with special attention to proper nutrition aimed to achieve the
      high end of normal BMI may help to reduce the high mortality and morbidity in
      hemodialysis patients.

PMID- 10201024
TI  - Activation of the tissue factor pathway occurs during continuous venovenous
      hemofiltration.
AB  - BACKGROUND: Activation of the tissue factor pathway occurs during continuous
      venovenous hemofiltration (CVVH). Despite adequate exogenous anticoagulation, the
      occlusion of CVVH circuits can occur within minutes to a few hours of use and is
      associated with evidence of thrombin generation. Having found no evidence of
      activation of the contact factor (intrinsic coagulation) pathway during CVVH, we
      sought to examine the effect of the first episode of CVVH on the tissue factor
      (extrinsic) pathway of coagulation and thrombin generation. METHODS: Twelve
      critically ill patients were studied prior to the commencement of hemofiltration
      and at regular intervals thereafter until the filter clotted. RESULTS: Prior to
      hemofiltration, most patients had increased levels of plasma tissue factor,
      thrombin-antithrombin (TAT) complexes, and tissue factor pathway inhibitor
      (TFPI); during hemofiltration, further generation of TAT complexes occurred.
      Initially, levels of activated factor VII (FVIIa) fell and TFPI increased, but
      during the course of hemofiltration, the levels of TFPI fell and FVIIa increased.
      Levels of tissue factor increased during CVVH in some patients, but this was not
      related to the generation of FVIIa. CONCLUSIONS: These data indicate that
      activation of FVII occurred during CVVH, which was related to levels of TFPI, but
      not tissue factor, and was coincidental to thrombin generation.

PMID- 10201025
TI  - Alport syndrome: is diagnosis only skin-deep?

PMID- 10201027
TI  - Obesity and mortality in ESRD: is it good to be fat?

PMID- 10201026
TI  - Estrogen: it's not just for reproduction any more.

PMID- 10201028
TI  - Genetics of diabetic nephropathy: evidence for major and minor gene effects.

PMID- 10201029
TI  - CT scan patterns of pulmonary alveolar proteinosis in children.
AB  - BACKGROUND: To study computed tomographic (CT) findings in children with
      pulmonary alveolar proteinosis (PAP) more extensively. OBJECTIVE: To describe the
      CT features at the time of diagnosis and after therapeutic broncho-alveolar
      lavage (BAL). MATERIALS AND METHODS: We retrospectively reviewed the CT scans of
      five children (aged 3 months to 4 years) examined because of incidental
      bronchitis (n = 1), disease in a sibling (n = 1) and relapsing fever, cough and
      dyspnoea (n = 3). Each patient had an initial CT scan. Two asymptomatic cases
      were not treated but were followed up by plain chest films. The other three had
      BAL and follow-up CT. RESULTS: Initial CT in all cases showed a diffuse
      reticulomicronodular pattern associated in three cases with posterior bilateral
      alveolar infiltrates. CT in the two asymptomatic patients remained unchanged or
      slightly improved without BAL. After BAL, a variable decrease of lung infiltrates
      was observed. CONCLUSIONS: Correlation between the extent of alveolar
      consolidation and severity of disease was found. Anatomical and pathological
      considerations allow us to consider that the classical reticulomicronodular
      pattern is not due to an interstitial infiltration but to alveoli filled with the
      abnormal material characteristic of PAP.

PMID- 10201030
TI  - Complicated pleural tuberculosis in children: CT evaluation.
AB  - PURPOSE: To describe the CT features of complicated pleural tuberculosis in
      children and to define the use of CT in children with pleural tuberculosis.
      MATERIALS AND METHODS: The CT findings in 11 children with complicated pleural
      tuberculosis were retrospectively analysed. CT was performed to evaluate
      persistent pleural thickening (n = 6) or a mass-like lesion (n = 5) detected on
      plain radiographs. Chest radiographs and medical records were reviewed to
      determine whether additional information provided by CT had altered clinical
      management. RESULTS: On CT, more than one location was involved in five patients
      (45%) and in two patients (18%) the entire pleural spaces were involved. Pleural
      thickening was seen in all 11 patients and enhancement after administration of
      contrast medium occurred in ten patients (91%). Low-density fluid collections
      were seen in nine patients (82%) and in two, CT revealed fluid collections within
      calcified pleural lesions. In five patients with mass-like lesions on plain
      radiographs, CT showed a low-density pleural mass with peripheral enhancement in
      four and a calcified pleural mass with fluid collection in one. CT demonstrated
      parenchymal abnormalities on the same side as pleural lesions in all 11 patients
      and hilar or mediastinal adenopathy in four. Four patients (36%) underwent
      surgery because of fluid within a calcified fibrothorax (n = 3) and chest wall
      tuberculosis (n = 1) that were seen only on CT. CONCLUSIONS: The CT features of
      complicated pleural tuberculosis in children were pleural thickening, enhancement
      and fluid collection with associated parenchymal abnormalities and
      lymphadenopathy. In the evaluation of children with pleural tuberculosis, CT can
      be useful for demonstrating fluid within a calcified fibrothorax or chest wall
      involvement, which usually requires surgical intervention.

PMID- 10201031
TI  - Radiation exposure during chest X-ray examinations in a premature intensive care
      unit: phantom studies.
AB  - BACKGROUND: There are few reports on the radiation dose received by infants,
      their family and radiographers exposed to scatter radiation in a premature baby
      intensive care unit. OBJECTIVE: To evaluate the degree of radiation exposure from
      diagnostic X-ray examinations with mobile X-ray machines in a premature intensive
      care unit. MATERIALS AND METHODS: The radiation exposure of an adjacent newborn,
      the radiographer and other persons in the room was simulated using phantoms
      during X-ray examination of the chest using vertical and horizontal beams.
      RESULTS: Most of the measured doses were below the registration limit of the
      measuring apparatus and had to be extrapolated by multiple exposures. Without
      exception, the maximal doses were significantly lower than the permitted limit
      for persons not professionally exposed to X-rays. CONCLUSIONS: Recommendations to
      avoid unnecessary radiation exposure are given.

PMID- 10201032
TI  - MR imaging of paediatric uterovaginal anomalies.
AB  - BACKGROUND: Transabdominal ultrasound (US) has not proved completely reliable in
      Mullerian duct anomalies. One study has shown it useful in obstructed
      uterovaginal anomalies. We are unaware of a study that has used endovaginal
      ultrasound in children to investigate uterovaginal anomalies. Magnetic resonance
      imaging (MRI) is now gaining wide acceptance in imaging congenital abnormalities
      of the genital tract. OBJECTIVE: To identify the problems and potential pitfalls
      of using MRI to evaluate the female genital tract in paediatric patients.
      MATERIALS AND METHODS: A retrospective review of the MRI scans of 19 patients,
      aged 3 months to 19 years (mean 14 years), with uterovaginal anomalies. RESULTS:
      The uterovaginal anomalies were categorised into three groups: (1) congenital
      absence of the Mullerian ducts, or the Mayer-Rokitansky-Kuster-Hauser syndrome (n
      = 7), (2) disorders of vertical fusion (n = 2) and (3) disorders of lateral
      fusion (n = 10). CONCLUSIONS: MRI is a reliable method for evaluating paediatric
      uterovaginal anomalies, but should be analysed in conjunction with other imaging
      modalities (US and genitography). Previous surgery makes interpretation more
      difficult and, if possible, MRI should be carried out prior to any surgery. An
      accurate MRI examination can be extremely helpful prior to surgery and it is
      important for the radiologist to have knowledge of how these complex anomalies
      are managed and what pitfalls to avoid.

PMID- 10201033
TI  - Complete duplication of bladder and urethra in the coronal plane in a girl: case
      report and review of the literature.
AB  - An unusual case of complete duplication of the bladder and urethra in the coronal
      plane associated with left ectopic kidney, duplication of the clitoris and a
      chondrolipomatous malformation in the pelvic region in a girl is reported. The
      accessory bladder was located posterolateral to the normal bladder and a ureteric
      opening into the accessory bladder was found. The malformation was initially
      identified by US and cystography and confirmed by cystoscopy.

PMID- 10201034
TI  - Intralobar bronchopulmonary sequestration in the newborn--a congenital
      malformation.
AB  - BACKGROUND: Intralobar sequestration (ILS) has been suggested to be an acquired
      lesion. However, we have observed several young infants who had ILS. OBJECTIVES:
      Since this fact seems to indicate a congenital origin, we reviewed our
      experience. MATERIAL AND METHODS: A retrospective review of bronchopulmonary
      sequestration from the Departments of Radiology and Pathology in Lund between
      1964 and 1997. RESULTS: We identified seven infants or young children with a
      diagnosis of intralobar sequestration. In each patient, the ILS was present
      before recurrent infection developed. Five had chest X-rays as neonates, one at 3
      months and one at 11 months of age. All but one showed an abnormality on their
      first chest X-ray, consistent with sequestration. Six of the ILS were verified at
      angiography; all seven were surgically removed. Two of the children with ILS also
      had congenital cystic adenomatoid malformation (CCAM). Three children had both
      ILS and scimitar syndrome. CONCLUSIONS: The fact that ILS was present in seven
      newborn and young infants indicates that this lesion is, at least in some
      patients, a congenital malformation.

PMID- 10201035
TI  - Renal sinus hyperechogenicity in acute pyelonephritis: description and
      pathological correlation.
AB  - This paper reports on the association between renal sinus hyperechogenicity and
      acute pyelonephritis. The medical records and imaging studies of 18 children
      displaying this pattern were retrospectively studied. Thickening of the renal
      pelvis and renal enlargement were the most frequent associated sonographic
      abnormalities. Further subtle findings can be found on sonography and
      colour/power Doppler. Their identification can help in the diagnostic approach to
      acute pyelonephritis and may obviate the need for other imaging modalities such
      as enhanced CT or 99mTc-DMSA scintigraphy. Renal sinus hyperechogenicity was also
      identified in a parallel study performed in female rabbits with experimental
      pyelonephritis and was shown, histologically, to be related to exudates of fibrin
      and polymorphonuclear leukocytes, interstitial oedema and micro-abscesses.

PMID- 10201036
TI  - Nephrogenic adenoma of the bladder: ultrasound demonstration. A case report.
AB  - A 4-year-old girl developed a space-occupying lesion in the bladder. This was
      demonstrated by US after resection of a huge ureterocoele and bilateral re
      implantation of ureters at 3 months of age and after three episodes of urinary
      tract infection. The mass developed outside the field of surgery and was removed
      endoscopically. Histology revealed a nephrogenic adenoma. US findings have not
      been emphasised previously. US should be useful in the detection of such lesions
      and for surveillance of recurrence.

PMID- 10201037
TI  - Macrocephaly and dilated Virchow-Robin spaces in childhood.
AB  - We report two children who presented with progressive macrocephaly and dilated
      Virchow-Robin spaces on magnetic resonance imaging. Follow-ups of 1-4 years and 5
      9 years, respectively, showed normal neuro-developmental progress. We suggest
      that dilated Virchow-Robin spaces in patients with macrocephaly is a benign
      association.

PMID- 10201038
TI  - Atypical herpes simplex encephalitis presenting as operculum syndrome.
AB  - This case report demonstrates the course of herpes simplex virus cerebritis in a
      patient aged 7 years 2 months who presented with non-specific symptoms followed
      by an epileptic attack. Subcortical, bilateral opercular and bilateral thalamic
      lesions were detected, but the temporal and inferior frontal lobes were spared.
      The patient developed anarthria, impairment of mastication and swallowing
      consistent with operculum syndrome. Diagnosis was made by magnetic resonance
      imaging and elevation of oligoclonal antibodies specific to herpes simplex virus
      in cerebrospinal fluid after an unexpectedly negative polymerase chain reaction
      test.

PMID- 10201039
TI  - Cerebellar atrophy: an important feature of carbohydrate deficient glycoprotein
      syndrome type 1.
AB  - We report three children, all younger than 2 years of age, presenting with
      cerebellar atrophy related to carbohydrate-deficient glycoprotein syndrome type
      1, an autosomal recessive metabolic disease. One patient had multisystem disease;
      two others had mental retardation with ataxia. In all cases the cerebellar
      atrophy was diagnosed on magnetic resonance imaging and, in one case, confirmed
      by autopsy. The cerebellar atrophy predominantly affected the anterior lobe.
      Vertical orientation of the tentorium cerebelli from the neonatal period in two
      cases suggests antenatal onset of the disease. Biological tests confirmed the
      diagnosis in all cases.

PMID- 10201040
TI  - Localised proton magnetic resonance spectroscopy of the brain after perinatal
      hypoxia: a preliminary report.
AB  - OBJECTIVES: Perinatal hypoxic ischaemic injury is a significant cause of
      neurodevelopmental impairment. The aim of this study was to evaluate localised
      proton magnetic resonance spectroscopy (1H-MRS) after birth asphyxia. MATERIALS
      AND METHODS: Thirty newborn infants suspected of having perinatal asphyxia (Apgar
      score < 3) were studied. The mean gestational age was 37 weeks, mean age at the
      MR examination was 18 days and mean weight was 2.9 kg. A 1.5-T unit was used for
      imaging and spectroscopy. None of the babies had mechanically assisted
      ventilation. No sedation was used. Axial T1-weighted and T2-weighted images were
      obtained. 1H-MRS was recorded in a single voxel, localised in white matter, using
      a STEAM sequence. RESULTS: Image quality was good in 25 of 30 babies. 1H-MRS was
      performed in 19 of 30 subjects, with adequate quality in 16. Choline,
      creatine/phosphocreatine and N-acetylaspartate peaks and peak-area ratios were
      analysed. Lactate was detected in four infants. The N-acetylaspartate/choline
      ratio was lower in infants with an impaired neurological outcome, but the
      difference was not statistically significant. CONCLUSIONS: This study suggests
      that 1H-MRS may be useful for assessing cerebral metabolism in the neonate. A
      raised lactate level and decreased N-acetylaspartate/choline ratio may be
      predictive of a poor outcome. However, in our experience this method is limited
      by the difficulty in performing the examination during the first hours after
      birth in critically ill babies, the problems related to use of a monovoxel
      sequence, the dispersion of the ratios and the lack of determination of the
      absolute concentration of the metabolites.

PMID- 10201041
TI  - Does the tuberous sclerosis complex include intracranial aneurysms? A case report
      with a review of the literature.
AB  - BACKGROUND: Tuberous sclerosis is a protean, genetically determined disease that
      may involve any organ or tissue and lead to a great number of symptoms and
      clinical features. OBJECTIVE: Diagnosis can be very difficult in cases with
      incomplete manifestations (formes fruste) lacking the classic signs of the
      disease. MATERIALS AND METHODS: We report a case fulfilling the diagnostic
      criteria for tuberous sclerosis (shagreen patches, hypomelanotic macules, renal
      cysts and angiomyolipomas, and "migration tracts" in the cerebral white matter)
      in association with a giant intracranial aneurysm, but lacking mental
      retardation, epilepsy and facial angiofibroma. RESULTS: Fourteen other cases of
      tuberous sclerosis and intracranial aneurysms, all but one without any clear sign
      of polycystic kidney disease, were found in the literature. CONCLUSION: We
      suggest that vascular dysplasias in general and aneurysms (mainly intracranial)
      in particular can be added to the other non-primary diagnostic features for the
      clinical diagnosis of tuberous sclerosis.

PMID- 10201042
TI  - Ischio-spinal dysostosis: a previously unrecognised combination of malformations.
AB  - BACKGROUND: Ischial hypoplasia is an extremely rare malformation, both as an
      isolated anomaly and as a syndromic constituent. OBJECTIVE: To elucidate the
      clinical and radiological characteristics in five patients with the combination
      of ischial hypoplasia and spinal malformations. MATERIALS AND METHODS: The
      clinical records and radiographs of two females and three males, ranging in age
      from 3 months to 38 years, were evaluated. RESULTS: Ossification defects of the
      ischial rami were symmetrical and total in four patients, whereas the right
      ischial ramus was partly ossified in the other patient. All patients possessed
      multiple segmental defects of the spine, with rib anomalies of varying severity.
      One patient characteristically showed multiple rib gaps, resulting in respiratory
      distress. Severe anomalies of the cervical spine were evident in two patients.
      Four patients exhibited lumbosacral hypoplasia, which ultimately led to cauda
      equina syndrome in three older patients. One patient had mild facial dysmorphism
      and another had a diversity of anomalies, including ichthyosiform skin changes.
      Four patients were sporadic cases, whereas the other patient was born to
      consanguineous parents. CONCLUSIONS: The combination of anomalies in these
      patients constitutes a recognisable pattern of malformations but may represent a
      heterogeneous group of disorders.

PMID- 10201043
TI  - Langer-Giedion syndrome associated with scimitar syndrome.
AB  - We describe an infant with Langer-Giedion syndrome combined with scimitar
      syndrome.

PMID- 10201044
TI  - Abnormal clavicles in a neonate with partial monosomy 21.
AB  - We report a newborn with partial monosomy 21, whose skeletal survey revealed
      strikingly abnormal clavicles.

PMID- 10201045
TI  - Ischaemic stroke due to traumatic carotid artery dissection.

PMID- 10201046
TI  - Stenting therapy for stenosing airway diseases.
AB  - Tracheobronchial stents have proved very valuable in the management of airway
      stenosis due to a variety of causes, both benign and malignant. These include
      benign strictures which are post-traumatic (e.g. after intubation), post
      anastomotic (e.g. after lung transplantation), or post inflammatory (e.g. after
      inflammatory conditions such as tuberculosis or Wegener's granulomatosis); as
      well as narrowing due to malignant involvement of large airways. In addition,
      airway stents have been used to treat tracheobronchomalacia and oesophageal
      airway fistulae. The insertion of the stent may need to be combined with other
      procedures such as airway dilatation, laser photocoagulation, brachytherapy or a
      mixture of these treatment modalities. Stents have been fashioned out of
      silicone, wire mesh or a combination of these materials, but the perfect stent
      has yet to be devised. Common problems include displacement and obstruction with
      secretions or granulation tissue. Less commonly the stent may perforate the
      airway wall, sometimes into the accompanying blood vessel. Nonetheless, airway
      stents are valuable tools in the management of airway narrowing.

PMID- 10201047
TI  - Stenting therapy for stenosing airway disease.
AB  - Stenosing airway disease is classified as intraluminal obstruction, extrinsic
      compression, and malacia by the anatomical site of the lesion. Stenting therapy
      is indicated for symptomatic relief of life-threatening dyspnea caused by the
      last two types. Airway stents are made with metal mesh and/or silicone rubber,
      and currently more than 20 kinds of stent are available. The metal stent (e.g.
      Gianturco stent, Wallstent) is easy to insert, may not need general anesthesia,
      and has wider internal lumen. Because it is very hard to reposition or remove, it
      is mainly used in malignant airway obstruction. Among many kinds of silicone
      stent, the Dumon stent is most widely used for benign and malignant airway
      stenoses, but general anesthesia and rigid bronchoscopy are needed for insertion.
      It can be removed when the stenosing airway disease subsides completely. In many
      clinical studies, most patients (85-90%) improved immediately after stenting, and
      procedure-related mortality is low (< 3%) in experienced centers. Stent
      displacement, mucus impaction, and granulation tissue formation are potential
      complications. Stenting is one of many effective therapeutic modalities for
      stenosing central airway disease. Careful patient selection, experiences, and
      continuous development of new technology will bring better results.

PMID- 10201048
TI  - Airway stenting in Japan.
AB  - Various types of outstanding airway stents have been made commercially available.
      In Japan, a total of 1004 airway stents (Dumon stents (Novatech, Aubagne,
      France), Gianturco Z stents (Cook Ins, Bloomington, USA), Ultraflex stents
      (Boston Scientific Corp, Natick, MA, USA), and Dynamic Y stents (Ruesch AG,
      Kernen, Germany)) were implanted from July 1991 until February 1998. Of all the
      various stents, the Dumon stent has become the standard worldwide. Also, the
      Dumon stent has been replacing the Gianturco Z stent as the preferred stent
      throughout Japan. The Dumon stent was the first stent covered by Japanese
      National Health Insurance. Therefore, we present our 5-year experience with the
      Dumon stent at our institution. In our experience, stenting is effective for the
      immediate and lasting relief of symptoms in patients with severe malignant
      obstruction of major airways.

PMID- 10201050
TI  - Increased perception of airway narrowing in patients with mild asthma.
AB  - To compare the perception of airway narrowing of nonasthmatic subjects with those
      having wheeze or mild asthma (doctor-diagnosed), the relationship between FEV1
      and breathlessness was examined in 123 subjects from a general population sample.
      Scores for breathlessness, using the Borg scale, were recorded before and after
      inhaling incremental doses of methacholine to a maximal dose of 196 mcmol or a
      maximum change in FEV1 of 50%. A history of asthma symptoms, including wheeze in
      the previous 12 months, and doctor-diagnosed asthma was obtained by
      questionnaire. At any given level of FEV1 there was wide variation in Borg scores
      between subjects, however median Borg scores and the mean slope of Borg score on
      FEVI was greater in the asthmatic subjects or those with wheeze compared with
      nonasthmatic subjects or those without wheeze. In both nonasthmatic and asthmatic
      subjects, those with airway hyperresponsiveness had increased maximum symptom
      scores and maximum changes in FEVI, but similar Borg scores relative to change in
      FEVI, compared with those without hyperresponsiveness. We conclude that the
      perception of mild and moderate degrees of airway narrowing varies widely between
      individuals but is increased in subjects with a history of mild asthma or wheeze
      in the last 12 months, independently of airway responsiveness.

PMID- 10201049
TI  - Benefit of in-phase chest wall vibration on the pulmonary hemodynamics in
      patients with chronic obstructive pulmonary disease.
AB  - OBJECTIVE: Chest wall vibration of contracting intercostal muscles (in-phase
      vibration, (IPV)) improves O2 saturation in patients with chronic obstructive
      pulmonary disease (COPD). The purpose of this study was to investigate the effect
      of IPV on the pulmonary hemodynamics in patients with COPD. METHODOLOGY: Twelve
      patients with COPD (FEV1%, 43.7 +/- 14.4%) underwent pulmonary artery
      catheterization in the supine position; hemodynamic variables as well as arterial
      and mixed venous gas tension were measured at baseline and after 15 min of IPV
      with IPV continued during the measurement. RESULTS: Mean pulmonary arterial
      pressure (Ppa, 21.3 +/- 5.0-19.1 +/- 4.8 mmHg and pulmonary vascular resistance
      (PVR, 294.6 +/- 196.0-228.5 +/- 101.7 dyne.sec.cm-5) decreased significantly, but
      there was no change in heart rate, cardiac index or systemic blood pressure. PaO2
      increased (66.5 +/- 10.3-70.0 +/- 9.7 Torr) and PaCO2 decreased (46.6 +/- 8.9
      45.0 +/- 10.1 Torr) significantly. Minute ventilation and tidal volume increased
      significantly in five out of the eight patients in whom ventilation was monitored
      throughout the study. CONCLUSION: IPV improves gas exchange and pulmonary
      circulation without affecting systemic circulation.

PMID- 10201051
TI  - Secretion of GM-CSF by inflammatory cells in the lung of patients with
      sarcoidosis.
AB  - Several cytokines are involved in the pathophysiology of sarcoidosis. Granulocyte
      macrophage colony-stimulating factor (GM-CSF) may be one of these cytokines
      because its mRNA is expressed by inflammatory cells obtained from the sarcoid
      lung. We thus asked two questions. Is GM-CSF secreted by bronchoalveolar lavage
      (BAL) cells? What type of cells express GM-CSF? GM-CSF secreted by the cultured
      BAL cells from 19 untreated sarcoid patients was measured by an enzyme-linked
      immunosorbent assay. The individual cells expressing GM-CSF mRNA were identified
      by in situ hybridization in seven patients. Spontaneous release of GM-CSF by BAL
      cells was demonstrated in one patient. When stimulated, BAL cells secreted GM-CSF
      in all subjects studied. In situ hybridization with digoxigenin-labelled GM-CSF
      cRNA probe revealed that the positive cells were round in shape and larger than
      lymphocytes, but smaller than large alveolar macrophages that are often irregular
      in shape. These results strongly indicated that small alveolar macrophages
      secrete GM-CSF in the sarcoid lesion. This phenomenon may contribute to the
      enhanced immunological activities observed in sarcoidosis.

PMID- 10201052
TI  - Comparative clinical and physiological features of Maori, Pacific Islanders and
      Europeans with sleep related breathing disorders.
AB  - Recent studies have suggested that there is a familial association of sleep
      apnoea syndrome and that this is not entirely explained by inheritance of known
      risk factors. Maori (M) and Pacific Islanders (PI) have many of the body habitus
      features associated with sleep apnoea and therefore might be expected to exhibit
      more severe disease than Europeans (E). OBJECTIVE: To compare the clinical and
      physiological characteristics of the different ethnic groups and to determine if
      race was an independent predictor of severity of sleep apnoea. METHODOLOGY: A
      prospective evaluation of patients attending the Sleep Disordered Breathing
      Clinic which serves the whole of Auckland (population 1.1 million), New Zealand
      was conducted for the period July 1994 to August 1995. The evaluation included
      history including a 26 question questionnaire, Epworth sleepiness score,
      examination, and where indicated, full polysomnography. RESULTS: A total of 233
      patients (154 E, 48 M and 33 PI), underwent full polysomnography. Forty-one (85%)
      of the M and 31 (94%) of PI had obstructive or mixed sleep apnoea compared with
      only 74 (49%) of the E (P < 0.0001; chi 2). There were few racial differences in
      the responses to the sleep questionnaire. M and PI were shown to have much
      greater neck and waist circumference and body mass indices. Severity parameters
      (apnoea-hypopnoea index, wake and minimum oxygen saturation, and apnoea duration)
      were greater for both M and PI compared with E (P < 0.001; Mann-Whitney U-test).
      Stepwise regression identified neck size, body mass index and age as independent
      predictors of severity. CONCLUSION: When other factors were controlled for, race
      was not an important independent predictor of severity of sleep apnoea.

PMID- 10201053
TI  - Tuberculous empyema.
AB  - The clinical courses of 35 tuberculous empyema patients were investigated
      retrospectively from November 1990 through November 1995. Most patients had
      nonspecific symptoms and signs but with far-advanced pulmonary parenchymal
      lesions in their chest roentgenographs. The effusions showed neutrophilic
      leukocytosis with a 60% positive culture rate for Mycobacterium tuberculosis.
      Multidrug resistant strains were found in 7 out of 18 cultures. All patients
      received chemotherapy and eight of them underwent additional surgical management.
      Twenty-two (62.9%) patients had been treated successfully and one patient is
      still under treatment. The remaining 12 patients either died during treatment or
      defaulted; and four (11.4%) of them had died of tuberculosis. We conclude that
      the treatment outcome of tuberculous empyema is less satisfactory than that of
      pulmonary tuberculosis, however, modern multidrug chemotherapy with repeated
      drainage and opportune surgical interventions could be in prospect of successful
      treatment of tuberculous empyema.

PMID- 10201054
TI  - Airway cough sensitivity to inhaled capsaicin and bronchial responsiveness to
      methacholine in asthmatic and bronchitic subjects.
AB  - The objective of this study was to evaluate the effect of chronic airway
      inflammation on airway cough sensitivity and non-specific bronchial
      responsiveness, and the relationship between them. The capsaicin cough threshold,
      defined as the lowest concentration of capsaicin causing five or more coughs, and
      non-specific bronchial responsiveness, defined as the methacholine concentration
      causing a 20% fall in forced expiratory volume in 1 s (FEV1) (PC20-FEV1), were
      measured in 18 asthmatic, 13 bronchitic (sinobronchial syndrome) and 28 healthy
      non-atopic subjects. All subjects were non-smoking men. The geometric mean values
      (mumol) of the cough threshold were 18.9 (GSEM 1.29), 8.69 (GSEM 1.29) and 27.6
      (GSEM 1.31) in asthmatic, bronchitic and normal subjects, respectively. The value
      in bronchitic subjects was significantly lower (P << 0.02) than that in normal
      subjects. The geometric mean value of PC20-FEV1 in asthmatic subjects (0.48 mg/ml
      (GSEM 1.38)) was significantly lower than that in bronchitic subjects (18.5 mg/ml
      (GSEM 1.75)) (P << 0.001). There was no correlation between cough threshold and
      PC20-FEV1 values (correlation coefficient (r) = 0.155). These results indicate
      that cough sensitivity is potentiated by chronic airway inflammation in
      bronchitis but not in asthma, and suggest that cough sensitivity and bronchial
      responsiveness may be independently potentiated by different mechanisms resulting
      from chronic airway inflammation.

PMID- 10201055
TI  - Sarcoidosis associated with multiple large pulmonary nodules.
AB  - Parenchymal manifestations of pulmonary sarcoidosis include a diffuse, symmetric,
      reticulonodular interstitial pattern, a fibrotic pattern, and an acinar pattern.
      Large pulmonary nodules in sarcoidosis are rare, and their frequency (> 1 cm in
      diameter) has been estimated at 2-4%. We report a rare case of sarcoidosis
      associated with large bilateral pulmonary nodules. These nodules reached up to 7
      cm in diameter, which is larger than any others reported previously. Furthermore,
      these nodular lesions developed within only 6 months of normal chest X-ray
      results and were not found to accompany bilateral hilar lymph adenopathy, which
      is observed in the usual course of sarcoidosis. As described above, this case of
      pulmonary sarcoidosis was significant not only in terms of the large size of the
      nodules but also the unique chest X-ray course.

PMID- 10201056
TI  - Transcatheter embolization of pulmonary arteriovenous malformations in Rendu
      Osler-Weber disease.
AB  - Interest in the treatment of the pulmonary arteriovenous malformations (PAVMs)
      that occur in approximately one-third of patients with Rendu-Osler-Weber (ROW)
      disease (hereditary haemorrhagic telangiectasia) has recently been renewed. PAVMs
      can now be occluded safely by the transvenous placement of detachable balloons or
      metal coils, thus avoiding the many potential complications of thoracotomy. This
      study analyses the treatment of eight PAVMs in four ROW patients by transcatheter
      embolization using detachable balloons or metal coils. After embolization, the
      mean right-to-left shunt fraction significantly decreased from 39.1 +/- 5.1% to
      11.9 +/- 1.1% (P < 0.05) and PaO2 significantly increased from 53.3 +/- 7.8 torr
      to 76.2 +/- 8.4 torr (P < 0.05). No serious complications occurred. One
      detachable balloon was deflated, but no recanalization occurred. We conclude that
      transcatheter embolization is a safe and efficacious treatment for PAVMs
      associated with ROW disease. Long-term studies are now needed to determine the
      risk of recanalization in this treatment.

PMID- 10201058
TI  - Empirical data is essential in understanding both sleepiness and MSLT.

PMID- 10201057
TI  - A silicosis patient presenting with an enlarged supraclavicular lymph node.
AB  - A stone splitter was discovered to have an enlarged supraclavicular lymph node
      which showed nodules with bi-refringent crystals on histological examination. He
      had worked in a dusty environment for more than 10 years with ineffective
      respiratory protection. He gave a history of occasional cough with blood-stained
      sputum for 10 years for which no definite diagnosis was made. Silicosis
      (classified as type s/s with profusion 1/1) was confirmed after his chest
      radiographs were reviewed. The presentation was unusual and illustrated the
      importance of an occupational history in clinical practice.

PMID- 10201059
TI  - Age-related changes in sleep in the rat.
AB  - Human sleep in old age is characterized by a number of changes, including
      reductions in sleep efficiency, amounts of visually scored slow-wave and REM
      sleep, and amplitude of the diurnal sleep/wake rhythm. In older rats, some, but
      not all, of these traits have been reported, including a decrease in the mean
      duration of sleep bouts, an increase in the number of sleep bouts, and a modest
      reduction of REM sleep. Studies of the diurnal rhythm of total sleep have had
      varied results. There are, however, virtually no data indicating at what point
      across the rat's lifetime the changes seen in old age begin to occur. In order to
      more fully characterize sleep in older rats, and to develop data on when they
      first appear, we have examined sleep in young adult (3 months), middle-aged (12
      months), and older (24 months) rats during 24 hours under constant dim light.
      Analyses of variance revealed no age-related changes in total sleep, NREM or REM
      sleep, wake time after sleep onset, or three different measures of the amplitude
      of the sleep/wake circadian rhythm. There were, however, significant age-related
      reductions in high-voltage NREM sleep ("HS2"), the mean length of sleep bouts,
      and REM-onset duration. These were seen in the 1-year-old rats, indicating that
      the changes seen in the older animals were evident by midlife.

PMID- 10201060
TI  - Genetic determinants of sleep regulation in inbred mice.
AB  - Genetic variation in the expression and regulation of sleep was assessed in six
      inbred mice strains (AK, C, B6, BR, D2, 129). The amount, distribution, and
      fragmentation of the behavioral states wakefulness (W), slow-wave sleep (SWS),
      and paradoxical sleep (PS), as well as EEG delta power in SWS, were determined
      and compared among strains and between baseline and recovery from a 6-hour sleep
      deprivation (SD) starting at lights-on. In baseline, the most striking strain
      differences concerned sleep amount, the onset and duration of the main rest
      period, and SWS fragmentation. The time course of delta power in SWS during the
      main rest period was similar between strains. Immediately following the SD, high
      delta power values were reached (higher for AK than for 129). However, the
      relative increase in delta power, compared to the first 6 hours of the baseline
      rest period, was not strain-specific. Over the first 6 hours of recovery, W was
      decreased and PS increased in AK, B6, BR, and 129. In C and D2, time spent in any
      of the states was not affected by the SD. In contrast, in the recovery dark
      period, SWS and PS were invariably increased. In recovery, SWS fragmentation was
      strongly reduced for D2, resulting in the disappearance of the strain differences
      observed in baseline. Since these inbred strains are fully homozygous and thus
      can be considered genetic clones, the sleep-related strain differences reported
      here can be attributed to differences in genotype. Therefore, this study provides
      a basis for the identification of genetic factors underlying sleep and its
      regulation.

PMID- 10201061
TI  - Dose-response relationship between sleep duration and human psychomotor vigilance
      and subjective alertness.
AB  - Although it has been well documented that sleep is required for human performance
      and alertness to recover from low levels after prolonged periods of wakefulness,
      it remains unclear whether they increase in a linear or asymptotic manner during
      sleep. It has been postulated that there is a relation between the rate of
      improvement in neurobehavioral functioning and rate of decline of slow-wave sleep
      and/or slow-wave activity (SWS/SWA) during sleep, but this has not been verified.
      Thus, a cross-study comparison was conducted in which dose-response curves (DRCs)
      were constructed for Stanford Sleepiness Scale (SSS) and Psychomotor Vigilance
      Task (PVT) tests taken at 1000 hours by subjects who had been allowed to sleep 0
      hours, 2 hours, 5 hours or 8 hours the previous night. We found that the DRCs to
      each PVT metric improved in a saturating exponential manner, with recovery rates
      that were similar [time constant (T) approximately 2.14 hours] for all the
      metrics. This recovery rate was slightly faster than, though not statistically
      significantly different from, the reported rate of SWS/SWA decline (T
      approximately 2.7 hours). The DRC to the SSS improved much more slowly than
      psychomotor vigilance, so that it could be fit equally well by a linear function
      (slope = -0.26) or a saturating exponential function (T = 9.09 hours). We
      conclude that although SWS/SWA, subjective alertness, and a wide variety of
      psychomotor vigilance metrics may all change asymptotically during sleep, it
      remains to be determined whether the underlying physiologic processes governing
      their expression are different.

PMID- 10201063
TI  - EEG spectral analysis of the sleep-onset period in narcoleptics and normal
      sleepers.
AB  - The sleep-onset period of 10 drug-free patients with narcolepsy-cataplexy and 10
      normals matched for age and gender was investigated using the multiple sleep
      latency test to elicit episodes of intentional sleep onset. Spectral analyses
      were calculated for delta, theta, alpha, sigma, and beta frequencies using 5
      second epochs beginning at lights-out and continuing until the first 2 minutes of
      stage 2 or REM sleep were reached, or until 20 minutes had elapsed. The sleep
      onset period was divided into quartiles, and mean root mean square (RMS)
      amplitude within each quartile was calculated. Mean delta amplitude was
      significantly higher across the sleep-onset period of narcoleptic REM naps and
      narcoleptic stage 2 naps compared to the sleep-onset period of normal stage 2
      naps or normal stage 1 naps. Mean theta amplitude was significantly higher for
      narcoleptic REM naps compared to normal stage 1 naps, and tended to be higher for
      narcoleptic stage 2 naps compared to normal stage 1 naps. Mean alpha amplitude
      was significantly lower for narcoleptic REM naps and narcoleptic stage 2 naps
      compared to normal naps containing just stage 1. Mean sigma amplitude was
      significantly lower for narcoleptic REM naps compared to normal stage 1 naps, and
      tended to be lower for narcoleptic REM naps compared to normal stage 2 naps. Mean
      beta amplitude did not differ between the narcoleptic and normal sleep-onset
      process. These findings support the existence of electrophysiologic differences
      within the microstructure of the process of sleep entry in narcoleptics and
      normals.

PMID- 10201062
TI  - Amplitude reduction in visual event-related potentials as a function of sleep
      deprivation.
AB  - Eight adult males were subjected to 40 hours of total sleep deprivation (TSD).
      Reaction time in a visual task and electroncephalographam (C3) were evaluated
      every 2 hours. One second of EEG before the stimuli was Fourier-transformed, and
      750 ms after target and nontarget stimuli were averaged and visual event-related
      potentials (ERP) were obtained. Factorial analysis identified time windows that
      showed significant amplitude reduction and longer latencies with TSD: (1) 140 to
      288 ms (P180-N242-P281); (2) 288 to 413 ms and 601 to 749 ms (N382; P718) and;
      (3) 531 to 601 ms (N500). Effect was strongest for N382 and P718, the amplitudes
      of which dropped to 20% of original size. The entire waveform recovered initial
      amplitudes and latencies after recovery sleep except for P718 latency. Waveforms
      within similar time intervals have been associated with attentional gating,
      sensory discrimination, target selection, uncertainty and decision processes.
      Amplitudes of the visual ERP were inversely correlated with hours of TSD,
      reaction time, and absolute power of the prestimulus EEG. Present results clearly
      show changes in fundamental neurophysiologic mechanisms as a result of TSD,
      indicating variability and reduction of the alertness mechanisms and changes in
      thalamocortical gating affecting attention, discrimination and decision-making.

PMID- 10201064
TI  - Are snoring medical students at risk of failing their exams?
AB  - STUDY OBJECTIVES: To compare the examination results of self-reported snoring and
      nonsnoring medical students DESIGN: We studied the examination scores obtained by
      medical students answering a multiple-choice test forming part of their final
      examinations. The students were asked to classify themselves as "nonsnorers,"
      "occasional snorers," or "frequent snorers," and to state their age, sex, height
      and weight. SETTING: University Hospital, Erlangen, Germany PARTICIPANTS: 201
      medical students (61% males/39% females; mean age 24.6 +/- 2.1 years; BMI 22.4 +/
      2.5 kg/m2) taking their final examinations in internal medicine. MEASUREMENTS
      AND RESULTS: Seventy-eight students (38.8%) claimed to be nonsnorers, 99 (49.3%)
      occasional snorers and 24 (11.9%) frequent snorers. The mean examination scores
      (adjusted for age, sex, and BMI) were 69.6 +/- 9.9% for the nonsnorers, 65.3 +/-
      10.0% for the occasional snorers and 62.0 +/- 8.2% for the frequent snorers (p <
      0.0001). 12.8% of the nonsnorers failed the exam, compared with 22.2% of the
      occasional snorers and 41.7% of the frequent snorers (p < 0.001). Logistic
      regression analysis showed an association between failing the exam and snoring (p
      = 0.013), but not between failure and age, BMI, or sex (relative risk for snorers
      adjusted for age, sex and BMI: 1.26; 95%--CI 1.01-1.57). CONCLUSIONS: In medical
      students, snoring seems to be associated with an increased risk of failing exams
      in a dose-response manner, even after controlling for age, sex and BMI. For the
      present, the mechanisms underlying this association must remain a matter of
      speculation. Snoring-related sleep fragmentation ("upper airway resistance
      syndrome") might be a causal factor.

PMID- 10201065
TI  - The detection of brief daytime sleep episodes.
AB  - INTRODUCTION: In the present study we evaluated the characteristics of sleep
      onset detection (during daytime nap opportunities) as a function of differing
      sleep lengths among healthy, asymptomatic subjects. METHODS: Twenty subjects were
      randomized into a Latin square design in which each subject received 1, 5, 10,
      and 20 minutes of sleep during an MSLT. Subjects were asked after each nap if
      they fell asleep. The rate of sleep detection was analyzed as a function of sleep
      duration. RESULTS: Three subjects detected sleep onset after 1 minute of sleep, 7
      subjects after 5 minutes of sleep, 10 subjects after 10 minutes of sleep, and 14
      after 20 minutes of sleep (chi 2 = 9.63, p < .05). CONCLUSIONS: The present data
      indicate the importance of sleep duration in an individual's ability to detect
      the occurrence of sleep. Importantly, only three subjects detected sleep after 1
      minute of sleep, emphasizing the dangerous nature of brief sleep episodes in the
      context of public safety.

PMID- 10201066
TI  - Sleep apnea in acute cerebrovascular diseases: final report on 128 patients.
AB  - Although obstructive sleep apnea (OSA) appears to be a cardiovascular risk
      factor, its frequency in patients with transient ischemic attack (TIA) and stroke
      remains poorly known. We prospectively studied 128 patients (mean +/- SD age = 59
      +/- 15 years) with stroke (n = 75) or TIA (n = 53). Assessment included body mass
      index (BMI); history of snoring and daytime sleepiness; cardiovascular risk
      factors and diseases; and severity of stroke (Scandinavian Stroke Scale = SSS).
      Polysomnography (PSG) was obtained in 80 subjects (group 1), a mean of 9 days
      (range, 1-71 days) after TIA or stroke. In 48 subjects (group 2), PSG was not
      available, refused, or inadequate. Groups 1 and 2 were similar with the exception
      of gender distribution. Clinical and PSG data were compared to those of 25
      healthy controls matched for age, gender, and BMI. An apnea-hypopnea index (AHI)
      > 10 was found in 62.5% of subjects and 12.5% of controls. Between patients and
      controls there was a significant difference in AHI (mean [range]: 28 (0-140) vs 5
      (0-24), p < 0.001), maximal apnea duration (mean + SD: 37 +/- 23 vs 23 +/- 13
      seconds, p = 0.009), and minimal oxygen saturation (mean + SD: 82 +/- 10% vs 90
      +/- 5%, p < 0.001). Conversely, frequency and severity of OSA were similar in
      stroke and TIA subjects. Multiple regression analysis identified age, BMI,
      diabetes, and SSS as independent predictors of AHI. Sleep apnea has a high
      frequency in patients with TIA and stroke, particularly in older patients with
      high BMI, diabetes, and severe stroke. These results may have implications for
      prevention, acute treatment, and rehabilitation of patients with acute
      cerebrovascular diseases.

PMID- 10201067
TI  - Health care utilization in the 10 years prior to diagnosis in obstructive sleep
      apnea syndrome patients.
AB  - Obstructive sleep apnea syndrome (OSAS) patients may have symptoms for years
      prior to recognition of their disorder, or they may be treated for the associated
      comorbidities. We hypothesized that such patients would be heavy consumers of
      health care resources for several years prior to diagnosis. We therefore compared
      health service utilization for a 10-year interval prior to diagnosis of 181 OSA
      patients to those of randomly selected age-, gender-, and geographically matched
      controls from the general population. OSAS patients used approximately twice as
      many health care services (as defined by physician claims and overnight stays in
      hospital) in the 10 years prior to their initial diagnostic evaluation for apnea.
      Physician claims for the OSA patients totaled $686,365 ($3972 per patient),
      compared to $356,376 ($1969 per patient) for the controls for the 10-year period
      examined in this study. Use of health services was significantly higher in 7 of
      10 years prior to diagnosis. The OSAS patients also had more overnight
      hospitalizations: they spent 1118 nights (6.2 per patient) in hospital vs 676
      nights (3.7 per patient) for controls in the decade prior to diagnosis. We
      conclude that by the time patients are finally diagnosed for sleep apnea, they
      have already been heavy users of health services for several years. It is
      possible that our findings reflect not OSAS per se, but the presence of some of
      the risk factors that predispose to OSAS, such as obesity, alcohol usage and
      perhaps tobacco consumption.

PMID- 10201068
TI  - Exhaled nitric oxide in patients with sleep apnea.
AB  - Cardiovascular diseases are frequent in patients with obstructive sleep apnea
      syndrome (OSAS), but the mechanisms underlying this association are largely
      unknown. Nitric oxide (NO) is a key regulatory element of vascular physiology.
      The concentration of NO in the exhaled air ([NOexh]) appears to be reduced in
      patients with systemic and pulmonary hypertension. This study sought to
      investigate whether [NOexh] is abnormal in patients with OSAS, and to explore
      potential relationships between [NOexh] and the severity of OSAS. We measured
      [NOexh] in 24 patients with OSAS (apnea-hypopnea index (AHI), 55 +/- 4 hour-1) (x
      +/- SEM), and in 7 healthy volunteers in whom OSAS was excluded clinically.
      [NOexh] was measured on line by a chemiluminescence analyzer (Dasibi
      Environmental Corporation, Glendale, Calif). Seven patients with OSAS (29%) had a
      positive history of cardiovascular disease. Mean [NOexh] was 19.7 +/- 3.2 ppb in
      healthy subjects, and 22.2 +/- 3.0 ppb in patients with OSAS (p = ns). [Noexh]
      was not significantly different in those patients with or without cardiovascular
      disease. [NOexh] was not significantly related to the AHI, the body mass index,
      or the arterial O2 saturation at night. These results show that [NOexh] is not
      abnormal in patients with OSAS, and that it does not relate to the presence of
      cardiovascular disease or to any of various common indices of disease severity.

PMID- 10201069
TI  - Dental side effects of an oral device to treat snoring and obstructive sleep
      apnea.
AB  - STUDY OBJECTIVES: Snoring and obstructive sleep apnea (OSA) are common and
      related conditions--with major social and health implications--which can be
      treated successfully with dental devices that reposition the mandible. Despite
      wide use, side effects of these devices have not yet been systematically
      evaluated. The purpose of the study was to evaluate side effects of a mandibular
      advancement splint (MAS) previously described by the authors. DESIGN:
      Questionnaire survey and dental examination of a consecutive case series of
      patients treated with the MAS SETTING: Dental outpatient clinic PATIENTS:
      Attempts were made to contact all 191 patients treated over a 5-year period. All
      had snored loudly and habitually with or without OSA prior to treatment.
      MEASUREMENTS AND RESULTS: Of 191 patients treated, 132 agreed to complete the
      questionnaire. All were scheduled to attend for dental examination and 106
      underwent examination. Of the 132 interviewed, patient and partner report
      indicated that the device was well tolerated and controlled snoring
      satisfactorily in 100 after 31 +/- 18 (mean +/- SD) months of use. Dental side
      effects were reported in 107 patients, although these were mostly minor, and only
      10 patients ceased using the device because of them. Side effects included excess
      salivation (in 40), xerostomia (in 30), temporomandibular joint pain (in 35),
      dental discomfort (in 35), myofacial discomfort (in 33) and bite changes (in 16).
      Of 106 patients examined, 30 had increased maximal opening and 76 had no change
      compared with pretreatment records. Temporomandibular joint noises were found in
      9 patients, and occlusal changes (12 m mylar strip and wax bite, relative to
      pretreatment) in 15. None of these effects could be related to degree of opening
      or protrusion produced by the MAS. CONCLUSION: Dental side effects occur in a
      significant proportion of patients using the MAS. In most cases these are minor
      and their importance must be balanced against the efficacy of the MAS in treating
      snoring and OSA.

PMID- 10201071
TI  - Bibliography of recent literature in sleep research.

PMID- 10201070
TI  - Native language shifts across sleep-wake states in bilingual sleeptalkers.
AB  - STUDY OBJECTIVES: To assess language used during episodes of sleeptalking in
      bilingual children. DESIGN: The investigation was accomplished through the
      parents who, after having received appropriate information, participated by
      filling out a survey on sleeptalking. SETTINGS: The study was performed in three
      bilingual schools of the Basque country, a region in northern Spain in which two
      completely different official languages are spoken. PATIENTS: A total of 1000
      parents agreed to participate, and 681 children were studied. MEASUREMENTS AND
      RESULTS: Sleeptalking was reported by 383 (56.3%) of children (mean age 9 years;
      range: 3-17). Most individuals used their dominant (i.e., native) language during
      sleep. However, a minority (< 4%) were found to use their non-dominant language
      persistently during episodes of sleeptalking. CONCLUSIONS: Balanced bilinguals
      (those who have equal proficiency in both languages) may sleeptalk in either of
      the two languages. Dominant bilinguals (i.e., having greater proficiency in one
      language) may preferentially sleeptalk in their dominant language, with immediate
      past events probably influencing language use in individual subjects on
      particular nights. Several considerations are postulated as an explanation for
      the group who systematically exhibited a dominance shift during sleep.

PMID- 10201073
TI  - A future for electron microscopy in cell biology?

PMID- 10201072
TI  - Looking at lipid rafts?
AB  - The notion that microdomains enriched in certain specialized lipids exist in
      membranes has been both attractive and controversial since it was first proposed
      that such domains, termed rafts, might act as apical sorting devices in
      epithelial cells. The observation that certain lipids are not extractable in cold
      nonionic detergent supports the raft concept, but the nature of the in vivo
      correlate of such detergent-resistant membranes remains enigmatic. In principle,
      microscopy should be able to determine whether the postulated rafts exist. This
      article focuses on recent microscopy experiments addressing this question.
      Several, but not all, results support the raft concept, but further definition of
      the structure, dynamics and function of lipid domains in various biological
      contexts is urgently required.

PMID- 10201074
TI  - Functional diversity in the dynamin family.
AB  - The function of the GTPase dynamin has been discussed for several years. It
      clearly plays a role in vesicle budding, but, despite recent insights, precisely
      how it functions in this process is still a matter of debate. In addition, it is
      now clear that dynamin is a member of a large protein family, present in a
      variety of cellular locations where members apparently perform a range of
      functions. This article describes current understanding of the structure and
      function of the various dynamin family members.

PMID- 10201075
TI  - Signal transduction by a protease cascade.
AB  - The dorsoventral axis of the Drosophila embryo is determined by a spatial cue
      generated by ovarian somatic cells. This cue is communicated to the embryo
      through an extracellular serine protease cascade active only on the ventral side
      of the embryo. Studies of the proteases and somatically expressed proteins
      involved in this signalling process suggest a working model for how the protease
      cascade is locally activated hours after the ovarian somatic cells have
      degenerated.

PMID- 10201076
TI  - Gettin' down with ubiquitin: turning off cell-surface receptors, transporters and
      channels.
AB  - G-protein-coupled receptors and transporters in Saccharomyces cerevisiae are
      modified with ubiquitin in response to ligand biding. In most cases, the
      proteasome does not recognize these ubiquitinated proteins. Instead,
      ubiquitination serves to trigger internalization and degradation of plasma
      membrane proteins in the lysosome-like vacuole. A number of mammalian receptors
      and at least one ion channel undergo ubiquitination at the plasma membrane, and
      this modification is required for their downregulation. Some of these cell
      surface proteins appear to be degraded by both the proteasome and lysosomal
      proteases. Recent evidence indicates that other proteins required for receptor
      internalization might also be regulated by ubiquitination, suggesting that
      ubiquitin plays diverse roles in regulating plasma membrane protein activity.

PMID- 10201077
TI  - The role of COP1 in repression of Arabidopsis photomorphogenic development.
AB  - Photomorphogenic development in Arabidopsis is regulated by the key repressor
      COP1, which interacts with specific transcription factors in the nucleus to
      modulate their activities. In the dark, COP1 accumulates in the nucleus and
      represses photomorphogenic development. Light diminishes the nuclear accumulation
      of COP1 and abrogates its repressor activity. A number of cellular components are
      involved in light-dependent nucleocytoplasmic partitioning of COP1, including the
      multisubunit COP9 complexes and at least three well-characterized photoreceptors.
      This review discusses current understanding of the mechanisms of COP1 action.

PMID- 10201078
TI  - Special-interest subgroups at the ASCB. Proceedings from the American Society for
      Cell Biology 38th annual meeting. San Francisco, California, USA. 12-16 December
      1998.
AB  - The annual meeting of the American Society for Cell Biology (ASCB) is a large and
      diverse gathering. At last year's meeting, there were over 8000 attendees, and
      the topics discussed covered many areas of cell biology. It would be impossible
      to cover the entire meeting within a trends in CELL BIOLOGY report, so instead we
      are focusing on an aspect of it that provided some of the most interesting and
      fruitful discussions. On Saturday afternoon, before the main symposia began,
      there were 11 special-interest subgroup meetings. The atmosphere at these
      meetings was informal, and they encouraged open and frank discussion of data and
      issues. This report provides a brief summary of the discussions at seven of the
      special-interest subgroup meetings.

PMID- 10201079
TI  - High-quality gynecological ultrasound can be highly beneficial, but poor-quality
      gynecological ultrasound can do harm.

PMID- 10201080
TI  - Advanced statistical techniques: how to use your data more effectively?

PMID- 10201081
TI  - Subjective assessment of adnexal masses with the use of ultrasonography: an
      analysis of interobserver variability and experience.
AB  - OBJECTIVE: The aim of the study was to evaluate the subjective assessment of
      ultrasonographic images for discriminating between malignant and benign adnexal
      masses. STUDY DESIGN: The study was prospective. Initially, one ultrasonographer
      preoperatively assessed 300 consecutive patients with adnexal masses.
      Subsequently, the recorded transparent photographic prints were independently
      assessed by five investigators, with different qualifications and level of
      experience, who were also given a brief clinical history of the patients (i.e.
      the age, menstrual status, family history of ovarian cancer, previous pelvic
      surgery and the presenting symptoms). The diagnostic performance of the observers
      was compared with the histopathology classification of malignant or benign
      tumors. The end-points were accuracy, interobserver agreement and the possible
      effect of experience. RESULTS: The first ultrasonographer and the most
      experienced investigator both obtained an accuracy of 92%. There was very good
      agreement between these two investigators in the classification of the adnexal
      masses (Cohen's kappa 0.85). The less experienced observers obtained a
      significantly lower accuracy, which varied between 82% and 87%. Their
      interobserver agreement was moderate to good (Cohen's kappa 0.52 to 0.76).
      CONCLUSION: Experienced ultrasonographers using some clinical information and
      their subjective assessment of ultrasonographic images can differentiate
      malignant from benign masses in most cases. The accuracy and the level of
      interobserver agreement are both correlated with experience. About 10% of masses
      were extremely difficult to classify (only < 50% of assessors were correct).

PMID- 10201082
TI  - Artificial neural network models for the preoperative discrimination between
      malignant and benign adnexal masses.
AB  - OBJECTIVE: The aim of this study was to generate and evaluate artificial neural
      network (ANN) models from simple clinical and ultrasound-derived criteria to
      predict whether or not an adnexal mass will have histological evidence of
      malignancy. DESIGN: The data were collected prospectively from 173 consecutive
      patients who were scheduled to undergo surgical investigations at the University
      Hospitals, Leuven, between August 1994 and August 1996. The outcome measure was
      the histological classification of excised tissues as malignant (including
      borderline) or benign. METHODS: Age, menopausal status and serum CA 125 levels
      and sonographic features of the adnexal mass were encoded as variables. The ANNs
      were trained on a randomly selected set of 116 patient records and tested on the
      remainder (n = 57). The performance of each model was evaluated using receiver
      operating characteristic (ROC) curves and compared with corresponding data from
      an established risk of malignancy index (RMI) and a logistic regression model.
      RESULTS: There were 124 benign masses, five of borderline malignancy and 44
      invasive cancers (of which 29% were metastatic); 37% of patients with a malignant
      or borderline tumor had stage I disease. The best ANN gave an area under the ROC
      curve of 0.979 for the whole dataset, a sensitivity of 95.9% and specificity of
      93.5%. The corresponding values for the RMI were 0.882, 67.3% and 91.1%, and for
      the logistic regression model 0.956, 95.9% and 85.5%, respectively. CONCLUSION:
      An ANN can be trained to provide clinically accurate information, on whether or
      not an adnexal mass is malignant, from the patient's menopausal status, serum CA
      125 levels, and some simple ultrasonographic criteria.

PMID- 10201083
TI  - The pattern of changes in ovarian stromal and uterine artery blood flow
      velocities during in vitro fertilization treatment and its relationship with
      outcome of the cycle.
AB  - OBJECTIVES: To assess the effect of short-term (2-3 weeks) pituitary suppression
      and controlled ovarian stimulation on ovarian and uterine artery Doppler
      measurements during the in vitro fertilization (IVF) treatment cycle and to
      compare the pattern of these changes between conception and non-conception cycles
      as well as between patients with normal and those with polycystic ovaries.
      DESIGN: Prospective observational study of women undergoing IVF treatment.
      SUBJECTS: Women using the long-treatment buserelin protocol who did not have
      uterine fibroids, ovarian cysts or endometrioma. METHODS: Serial transvaginal
      color and pulsed Doppler measurements of ovarian stromal and uterine artery blood
      flow velocity were carried out in the early follicular phase of the menstrual
      cycle, on the day of pituitary suppression and on the day of administration of
      human chorionic gonadotropin (hCG). The main outcome measures were the ovarian
      stromal and uterine artery blood flow peak systolic velocity (PSV) and
      pulsatility index (PI). RESULTS: A total of 105 patients were recruited but six
      patients were excluded from the analysis because they had only one stage of the
      measurements performed. There was a significant decline in mean ovarian stromal
      artery PSV after 2-3 weeks of gonadotropin releasing hormone (GnRH) agonist
      therapy but no effect on ovarian stromal artery PI. The mean uterine artery PSV
      or PI did not change significantly after 2-3 weeks of GnRH agonist therapy. There
      was a significantly higher mean ovarian stromal artery PSV in conception cycles
      compared to non-conception cycles in the early follicular phase and on the day of
      pituitary suppression, but not on the day of hCG administration. There were no
      differences between conception and non-conception cycles in the mean uterine
      artery PSV or PI. Women with polycystic ovaries had a higher mean ovarian artery
      PSV on all the three occasions of measurement. CONCLUSION: These data suggest
      that assessment of ovarian blood flow before commencement of gonadotropin
      stimulation may play a role in assessing cycles likely to result in pregnancy.

PMID- 10201084
TI  - Color Doppler study of the venous circulation in the fetal brain and hemodynamic
      study of the cerebral transverse sinus.
AB  - OBJECTIVES: To describe the venous circulation in the fetal brain; to describe
      the normal blood flow velocity waveform in the transverse sinus and to establish
      normal reference ranges for the second half of gestation. POPULATION: A total of
      126 pregnant women with uncomplicated pregnancies at 20-42 weeks of gestation.
      METHODS: A combination of color-coded Doppler and two-dimensional real-time
      ultrasound was used to identify the main venous systems in the fetal brain. Blood
      flow velocity waveforms of the transverse sinus were obtained from a transverse
      plane of the head at the level of the cerebellum. RESULTS: A waveform could be
      obtained in the cerebral transverse sinus in 98% of the cases. The waveform
      obtained was triphasic with a forward systolic component, a forward early
      diastolic component and a lower forward component in late diastole. Reverse flow
      during atrial contraction was seen before 28 weeks and the diastolic flow
      increased with gestation thereafter. Pulsatility and resistance indices decreased
      and flow velocities increased in the transverse sinus throughout gestation.
      CONCLUSION: The venous circulation of the fetal brain can be identified by color
      Doppler. The gestational age-related decrease in resistance and increase in flow
      velocities suggest that hemodynamic studies of the cerebral transverse sinus
      might have clinical implications in studying compromised fetuses.

PMID- 10201085
TI  - Neurological morbidity after fetal supraventricular tachyarrhythmia.
AB  - BACKGROUND: Fetal tachyarrhythmia is a well-documented entity which, in the
      absence of pharmacological intervention, may lead to congestive heart failure,
      fetal hydrops and eventually fetal demise. The success rate of the implemented
      treatment is generally measured by survival and achievement of control of the
      arrhythmia. We report on the occurrence of associated cerebral damage in three
      patients with fetal tachycardia. METHODS: We describe three patients with a
      history of fetal supraventricular tachyarrhythmia who developed cerebral
      complications in utero. RESULTS: Two patients had cerebral hypoxic-ischemic
      lesions and one had hemorrhagic lesions present at birth. They had developed
      severe congestive heart failure and fetal hydrops secondary to fetal
      tachyarrhythmia, and there were no other obvious causes for the cerebral
      pathology. Two of these patients were referred to us antenatally. Therapy was
      instituted and resulted in control of the tachycardia and resolution of hydrops.
      The third patient was referred to our clinic shortly after birth because of
      severe circulatory problems secondary to fetal tachyarrhythmia. CONCLUSION: From
      these observations, we believe that a fetus with tachyarrhythmia and subsequent
      hydrops is at increased risk for the development of cerebral complications, due
      to the circulatory disturbances and sudden changes in heart rate which may lead
      to fluctuations in cerebral perfusion. This would imply that it is of the utmost
      importance to aim at immediate and complete control of the heart rate in the
      treatment of fetal tachyarrhythmia.

PMID- 10201086
TI  - Cardiac blood flow studies in fetuses with homozygous alpha-thalassemia-1 at 12
      13 weeks of gestation.
AB  - OBJECTIVE: Fetuses affected by homozygous alpha-thalassemia-1 develop anemia as
      early as the first trimester. Our objective was to study hemodynamic indices in
      affected fetuses at 12-13 weeks of gestation to determine whether these would be
      useful in the prediction of anemia. DESIGN: Prospective observational study.
      SUBJECTS: Women referred before 14 weeks of gestation for the prenatal diagnosis
      of homozygous alpha-thalassemia-1. METHODS: Transabdominal and/or transvaginal
      Doppler sonography was performed to measure the flow velocities in the fetal
      ascending aorta and pulmonary artery at 12-13 weeks. The Doppler indices were
      compared between those that were subsequently confirmed to be affected by
      homozygous alpha-thalassemia-1 and those that were unaffected. RESULTS: Between
      June 1997 and April 1998, 60 eligible women were recruited. Doppler examination
      was successful in 58 fetuses. Of these, 22 were subsequently confirmed to be
      affected by homozygous alpha-thalassemia-1. The diagnosis was made by chorionic
      villus sampling and DNA analysis in two affected fetuses and by cordocentesis and
      hemoglobin evaluation in 20 affected fetuses. Hemoglobin concentrations could be
      measured in ten fetuses and these ranged from 4 to 8 g/dl. The affected fetuses
      had significantly higher peak velocities at the pulmonary valve and ascending
      aorta and a larger inner diameter of the pulmonary valve than that in unaffected
      fetuses. The total cardiac output was increased by one-third in affected fetuses
      and was mainly due to an increase of the right-side cardiac output. CONCLUSION:
      In the early stage of anemia, the fetus responds mainly by increasing its right
      side cardiac output. However, there is extensive overlap of the values of cardiac
      output between the affected and the unaffected fetuses, precluding its use in the
      prediction of anemia.

PMID- 10201087
TI  - Validation of diameter measurements by ultrasound: intraobserver and
      interobserver variations assessed in vitro and in fetal sheep.
AB  - OBJECTIVES: Blood flow evaluation in the fetus is hampered by inaccuracy in the
      measurement of vessel diameter. The impact of biological variation on
      reproducibility studies is unknown. The present study evaluated diameter
      measurements carried out with modern ultrasound equipment by assessing inter- and
      intraobserver variations. DESIGN: Repeated measurements analyzed by a general
      factorial model of analysis of variance. METHODS: Three observers measured
      repeatedly (six or more times for each tube and session) silicone tube implants
      (0.6, 2.2 and 6 mm), applying ultrasound imaging in eight fetal sheep, and the
      same silicone tubes in vitro. Analysis of variance was carried out on 199
      observations made in vitro and 537 in vivo. RESULTS: The upper 95% confidence
      limit for the intra- and interobserver variations was higher for measurements
      made in vivo than in vitro. It was highest for the largest diameter and varied
      between 0.10 and 0.38 mm. When the diameter was determined as an average of
      repeated measurements, the error was reduced: six measurements in vivo had upper
      95% confidence limits for intraobserver variation of 0.04 and 0.09 mm for
      diameters of 0.6 and 6 mm, respectively. CONCLUSIONS: The results show that
      ultrasound diameter measurements have a high reproducibility even for vessels of
      small dimensions when repeated measurements are taken with high-frequency
      ultrasound under favorable conditions. The low variation described in the present
      investigation of silicone tubes, compared to previous studies, suggests that
      diameter changes of living vessels represent a separate source of measurement
      variation.

PMID- 10201088
TI  - Perinatal outcome in pregnancies with a positive serum screening for Down's
      syndrome due to elevated levels of free beta-human chorionic gonadotropin.
AB  - OBJECTIVE: To evaluate the potential clinical use of maternal serum free beta
      human chorionic gonadotropin (beta-hCG) and uterine artery Doppler investigation
      to screen for placenta-related adverse outcome in pregnancies at positive risk
      for Down's syndrome at 15-18 weeks. DESIGN: A cohort of 329 consecutive pregnant
      women with a singleton viable pregnancy and a positive risk for Down's syndrome
      was retrospectively investigated. This group was obtained from an unselected
      population of 3952 women attending the same hospital over a 2-year period. Using
      the results of this first analysis, we selected a group of 26 women with
      unexplained high levels of free beta-hCG and followed them prospectively with
      monthly ultrasound and uterine artery Doppler examinations. RESULTS: In the
      retrospective cohort, risk ratios stratified for maternal serum beta-hCG multiple
      of the median (MoM) values indicated that the highest incidence of adverse
      pregnancy outcome was in those women with values of > or = 5.0. In the
      prospective study, pregnancy outcome was complicated by uteroplacental disorders
      in eight cases. Analysis of the Doppler investigation indicated that, in women
      with a very high level of hCG, an abnormally high uterine artery pulsatility
      index (PI) had lower sensitivity and negative predictive value than early
      diastolic notch, whereas the specificity and positive predictive value were
      higher for a high uterine artery PI. CONCLUSIONS: These findings suggest an
      association between a high level of maternal serum beta-hCG at 15-18 weeks, the
      presence of an early diastolic notch in the uterine artery flow velocity waveform
      and adverse pregnancy outcome due to abnormal development of the uteroplacental
      circulation. Young women with an unexplained high beta-hCG level would benefit,
      apart from detailed sonography of the fetus and/or karyotyping, from uterine
      Doppler investigation and counselling about the follow-up and management of
      placenta-related pregnancy disorders.

PMID- 10201089
TI  - Arteriovenous malformation of mesosalpinx associated with a 'vanishing' ectopic
      pregnancy: diagnosis with three-dimensional color power angiography.
AB  - We describe two cases of pelvic arteriovenous malformation diagnosed with the aid
      of three-dimensional color power angiography. In both cases, beta-human chorionic
      gonadotropin (beta-hCG) increased to significant levels (8413 and 1560 mIU/ml,
      respectively); however, neither an intrauterine nor an adnexal gestational sac
      could be found. In each case, we observed an adnexal mass with several tortuous
      areas exhibiting abundant turbulent flow. The diagnosis of arteriovenous
      malformation was made and further assessment by three-dimensional color power
      angiography and magnetic resonance imaging (MRI) was carried out. The complex
      vascular anatomy of arteriovenous malformation, including its feeding vessels and
      drainage, was clearly depicted by three-dimensional color power angiography and
      correlated well with magnetic resonance angiography. Levels of beta-hCG decreased
      in subsequent tests, and eventually became negative 2-3 months later without and
      intervention. We believe that an involutional ectopic pregnancy induced the rapid
      growth of the arteriovenous malformations within the mesosalpinx. Three
      dimensional color power angiography can be performed quickly and easily, using
      existing ultrasound equipment. It improves our understanding of complicated
      vasculature, and thus is a useful adjunct to two-dimensional and color Doppler
      ultrasound in the diagnosis of arteriovenous malformation.

PMID- 10201090
TI  - Trisomy 10: first-trimester features on ultrasound, fetoscopy and postmortem of a
      case associated with increased nuchal translucency.
AB  - We report a case of the prenatal diagnosis of trisomy 10 in a fetus presenting
      with an increased nuchal translucency thickness (5 mm) on a routine first
      trimester anomaly scan at 12 weeks' gestation. Multiple abnormalities were
      diagnosed by ultrasound and fetoscopy. Karyotyping on chorionic villus sampling
      led to the diagnosis of homogeneous trisomy 10 which was confirmed by in situ
      hybridization on fetal tissue samples. Postmortem examination confirmed major
      anatomical malformations, including facial cleft, arthrogryposis of the upper and
      lower limbs and bilateral diaphragmatic hernia, and also revealed hypoplastic
      lungs, right renal agenesis and a complex cardiac malformation. Trisomy 10 is an
      uncommon chromosomal abnormality that is likely to be associated with increased
      fetal nuchal translucency. This case also emphasizes the value of a detailed
      anomaly scan in high-risk patients in the first trimester of pregnancy.

PMID- 10201091
TI  - Abnormal prenatal sonographic findings in the posterior cranial fossa: a case of
      Joubert's syndrome.
AB  - Joubert's syndrome is a well-documented but rare disorder characterized by a
      variable combination of central nervous system, respiratory, renal and eye
      anomalies. The most significant and constant neuropathological finding is partial
      or complete agenesis of the cerebellar vermis. The syndrome was first described
      by Joubert and colleagues as a familial agenesis of the cerebellar vermis and
      appears to be inherited as an autosomal recessive trait. A case of Joubert's
      syndrome is described in which second-trimester ultrasonography demonstrated
      abnormal findings in the fetal posterior fossa with associated renal
      abnormalities. However, postnatal sonography of the posterior fossa could not
      confirm the prenatal findings, and the diagnosis of Joubert's syndrome was only
      later established by computed tomography of the neonatal brain in the knowledge
      of the characteristic clinical picture.

PMID- 10201092
TI  - Prenatal sonographic diagnosis of type I achondrogenesis with a large cystic
      hygroma.

PMID- 10201094
TI  - Distribution of ATPase and ATP-to-ADP phosphate exchange activities in magnesium
      chelatase subunits of Chlorobium vibrioforme and Synechocystis PCC6803.
AB  - Insertion of magnesium into protoporphyrin IX is a complex ATP-dependent reaction
      catalysed by the enzyme Mg-chelatase. Three separate proteins (Mg-chelatase
      subunits), designated as D, H and I, are involved in the chelation reaction. The
      genes encoding the Mg-chelatase subunits of the green sulfur bacterium Chlorobium
      vibrioforme and of the cyanobacterium Synechocystis strain PCC6803 were expressed
      in Escherichia coli. The recombinant proteins were purified, tested for ATPase
      and phosphate exchange activities, and compared with the activities of the
      corresponding subunits of Rhodobacter sphaeroides. The Synechocystis strain
      PCC6803 I subunit and the C. vibrioforme H and I subunits hydrolysed ATP at the
      rates of 2.0, 1.8 and 0.16 nmol (mg protein)-1 min-1, respectively. The ATPase
      activity of the C. vibrioforme H subunit was similar to that reported for the R.
      sphaeroides H subunit. The Synechocystis strain PCC6803 H subunit failed to
      hydrolyse ATP. The I subunit of Synechocystis strain PCC6803 and C. vibrioforme
      catalysed a transfer of PO4 from ATP to ADP (exchange activity) at the rate of
      1.75 +/- 0.15 nmol (mg protein)-1 min-1. This exchange rate was 300-fold lower
      than that reported for the R. sphaeroides I subunit. The PO4 exchange activities
      were correlated with the presence of the sequence GXRGTGKSTXVRALA in the primary
      structure of the three I subunits. Mg-chelatase activity was reconstituted by
      combining the three subunits of the same bacterium [rates of 41-89 pmol Mg
      deuteroporphyrin (mg protein)-1 min-1]. Heterologous subunit combinations
      resulted in low or no Mg-chelatase activity.

PMID- 10201093
TI  - Selective transport of divalent cations by transition metal permeases: the
      Alcaligenes eutrophus HoxN and the Rhodococcus rhodochrous NhlF.
AB  - nhlF and hoxN, the genes encoding a cobalt transporter of Rhodococcus rhodochrous
      J1 and a nickel permease of Alcaligenes eutrophus H16, respectively, were
      expressed in Escherichia coli. 57CO2+ and 63Ni2+ transport of the recombinants
      was examined by means of a previously described physiological assay. Although the
      transporters are highly similar, different preferences for divalent transition
      metal cations were observed. HoxN was unable to transport 57CO2+, but mediated
      63Ni2+ uptake. The latter activity was unaffected by a tenfold excess of other
      divalent cations, showing the specificity of HoxN for Ni2+. In contrast, NhlF
      transported both 57CO2+ and 63Ni2+ ion. NhlF-mediated 63Ni2+ uptake was markedly
      reduced in the presence of CO2+, while 57CO2+ uptake was only slightly lower in
      the presence of Ni2+. These results indicate different affinities of NhlF for
      CO2+ and Ni2+ and identified CO2+ ion as the preferred substrate.

PMID- 10201095
TI  - Cell wall of Thermoanaerobacterium thermosulfurigenes EM1: isolation of its
      components and attachment of the xylanase XynA.
AB  - Thermoanaerobacterium thermosulfurigenes EM1 has a gram-positive type cell wall
      completely covered by a surface layer (S-layer) with hexagonal lattice symmetry.
      The components of the cell envelope were isolated, and the S-layer protein was
      purified and characterized. S-layer monomers assembled in vitro into sheets with
      the same hexagonal symmetry as in vivo. Monosaccharide analysis revealed that the
      S-layer is associated with fucose, rhamnose, mannosamine, glucosamine, galactose,
      and glucose. The N-terminal 31 amino acid residues of the S-layer protein showed
      significant similarity to SLH (S-layer homology) domains found in S-layer
      proteins of different bacteria and in the exocellular enzymes pullulanase,
      polygalacturonate hydrolase, and xylanase of T. thermosulfurigenes EM1. The
      xylanase from T. thermosulfurigenes EM1 was copurified with the S-layer protein
      during isolation of cell wall components. Since SLH domains of some structural
      proteins have been shown to anchor these proteins noncovalently to the cell
      envelope, we propose a common anchoring mechanism for the S-layer protein and
      exocellular enzymes via their SLH domains in the peptidoglycan-containing layer
      of T. thermosulfurigenes EM1.

PMID- 10201096
TI  - The cell wall porin of the gram-positive bacterium Nocardia asteroides forms
      cation-selective channels that exhibit asymmetric voltage dependence.
AB  - Detergent-solubilized cell wall extracts of the gram-positive, strictly aerobic
      bacterium Nocardia asteroides contain channel-forming activity as judged from
      reconstitution experiments using lipid bilayer membranes. The cell wall porin was
      identified as a protein with an apparent molecular mass of about 84 kDa based on
      SDS-PAGE. The porin was purified to homogeneity using preparative SDS-PAGE. The
      84-kDa protein was no longer observed after heating in SDS buffer. The presumed
      dissociation products were not observed on SDS-polyacrylamide gels. The cell wall
      porin increased the specific conductance of artificial lipid bilayer membranes
      from phosphatidylcholine/phosphatidylserine mixtures by the formation of cation
      selective channels, which had an average single-channel conductance of 3.0 nS in
      1 M KCl. The single-channel conductance was only moderately dependent on the bulk
      aqueous KCl concentration, which indicated negative point charge effects on the
      channel properties. The analysis of the concentration dependence of the single
      channel conductance using the effect of negative charges on channel conductance
      suggested that the diameter of the cell wall channel is about 1.4 nm. Asymmetric
      addition of the cell wall porin to lipid bilayer membranes resulted in an
      asymmetric voltage dependence. The cell wall channel switched into substates,
      when the cis side of the membrane, the side of the addition of the protein, had
      negative polarity. Positive potentials at the cis side had no influence on the
      conductance of the cell wall channel.

PMID- 10201097
TI  - Diversity of chlorophenol-degrading bacteria isolated from contaminated boreal
      groundwater.
AB  - Chlorophenol-degrading bacteria from a long-term polluted groundwater aquifer
      were characterized. All isolates degraded 2,4,6-trichlorophenol and 2,3,4,6
      tetrachlorophenol at concentrations detected in the contaminated groundwater (<
      10 mg 1(-1)). Pentachlorophenol was degraded by three isolates when present
      alone. In two gram-positive isolates, 2,3,4,6-tetrachlorophenol was required as
      an inducer for the degradation of pentachlorophenol. The gram-positive isolates
      were sensitive to pentachlorophenol, with an IC50 value of 5 mg/l. Isolates
      belonging to the Cytophaga/Flexibacter/Bacteroides phylum had IC50 values of 25
      and 63 mg/l. Isolates belonging to alpha-, beta- and gamma-Proteobacteria
      generally tolerated the highest pentachlorophenol concentrations (> 100 mg/l).
      Polychlorophenol-degrading capacity was found in strains of Nocardioides,
      Pseudomonas, Ralstonia, Flavobacterium, and Caulobacter previously not known to
      degrade polychlorophenols. In addition, six polychlorophenol-degrading
      sphingomonads were found.

PMID- 10201098
TI  - Cryptic luminescence in the cold-water fish pathogen Vibrio salmonicida.
AB  - The recent discovery that the fish pathogen Vibrio salmonicida is closely related
      to the luminous bacteria Vibrio fischeri and Vibrio logei suggested that V.
      salmonicida might also be capable of bioluminescence. Interestingly, cells of V.
      salmonicida were found to produce light in culture, but only when exposed to
      either an aliphatic aldehyde and/or the major V. fischeri autoinducer N-(3-oxo
      hexanoyl)-L-homoserine lactone, a transcriptional activator of the luminescence
      (lux) genes. An extract of spent medium of V. salmonicida that should contain any
      V. salmonicida acyl-homoserine lactone autoinducer, when added to V. fischeri
      cells, led to an induction of their luminescence. These results show that V.
      salmonicida is a newly recognized luminous bacterial species that apparently both
      produces an autoinducer activity and responds to exogenous V. fischeri
      autoinducer.

PMID- 10201099
TI  - Isolation of salt-induced periplasmic proteins from Synechocystis sp. strain PCC
      6803.
AB  - Periplasmic proteins were obtained from control cells and salt-adapted cells of
      the cyanobacterium Synechocystis sp. PCC 6803 using the method of cold osmotic
      shock. Two of these proteins (PP 1, apparent mol. mass 27.6 kDa, and PP 3,
      apparent mol. mass 39.9 kDa) were accumulated in high amounts in the periplasm of
      salt-adapted cells, while the major periplasmic protein (PP 2, apparent mol. mass
      36.0 kDa) was accumulated independently from salt. After isolation from gels and
      partial sequencing, the proteins could be assigned to proteins deduced from the
      complete genome sequence of Synechocystis. Neither salt-induced periplasmic
      proteins (PP 1, Slr0924 and PP 3, Slr1485) exhibited sequence similarity to
      proteins of known function from databases. The major protein (PP 2-Slr0513)
      showed significant sequence similarities to iron-binding proteins. All proteins
      included typical leader sequences at their N-terminus.

PMID- 10201100
TI  - Side effects of extinction: prevalence of bursting and aggression during the
      treatment of self-injurious behavior.
AB  - Findings from basic and applied research suggest that treatment with operant
      extinction may produce adverse side effects; two of these commonly noted are an
      increase in the frequency of the target response (extinction burst) and an
      increase in aggression (extinction-induced aggression). Although extinction is
      often used to treat problem behavior in clinical settings, few applied studies
      have examined the prevalence of these side effects or their possible attenuation
      with other operant procedures. An analysis of 41 data sets for individuals who
      received treatment for self-injurious behavior indicated that extinction bursts
      or increases in aggression occurred in nearly one half of the cases. The
      prevalence of bursting and aggression was substantially lower when extinction was
      implemented as part of a treatment package rather than as the sole intervention.

PMID- 10201101
TI  - Reduction of stimulus overselectivity with nonverbal differential observing
      responses.
AB  - Three individuals with mental retardation exhibited stimulus overselectivity in a
      delayed matching-to-sample task in which two sample stimuli were displayed on
      each trial. Intermediate accuracy scores indicated that participants could match
      one of the samples but not both of them. Accuracy in a baseline condition was
      compared to accuracy with a differential observing response procedure. This
      procedure prompted participants to make simultaneous identity-matching responses
      that required observation and discrimination of both sample stimuli. These
      observing responses were never followed by differential consequences. When
      observing responses were prompted, participants' accuracy scores improved. In a
      return to the baseline condition, when differential observing responses were no
      longer prompted, accuracy returned to intermediate levels. The results show that
      stimulus overselectivity can be greatly reduced by a behavioral intervention that
      controls observing behavior and verifies discrimination, but that exposure to
      such procedures alone may be insufficient for lasting benefits.

PMID- 10201102
TI  - Further analysis of the separate and interactive effects of methylphenidate and
      common classroom contingencies.
AB  - We evaluated separate and interactive effects between common classroom
      contingencies and methylphenidate (MPH) on disruptive and off-task behaviors for
      4 children with a diagnosis of attention deficit hyperactivity disorder. Analogue
      conditions consisting of contingent teacher reprimands, brief time-out, no
      interaction, and alone were conducted in a multielement design. Medication status
      (MPH or placebo) was alternated across days in a superordinate multielement
      design. Results indicate that (a) the behavioral effects of MPH were influenced
      by one or more of the analogue conditions for each participant, and (b) time-out
      was associated with zero or near-zero levels of both disruptive and off-task
      behavior for 3 of the 4 participants during MPH and placebo conditions.
      Implications for the clinical effectiveness of MPH and possible behavioral
      mechanisms of action of MPH in applied settings are discussed.

PMID- 10201103
TI  - On the relation between object manipulation and stereotypic self-injurious
      behavior.
AB  - Results from a number of studies have shown an inverse relationship between
      stereotypic behavior and object manipulation. The purposes of this study were to
      determine whether techniques similar to those used previously (prompting and
      reinforcement) would be effective in increasing object manipulation under both
      prompted and unprompted conditions, and to ascertain whether increases in object
      manipulation would result in decreases in stereotypic self-injurious behavior
      (SIB). Two individuals with developmental disabilities who engaged in SIB
      maintained by automatic reinforcement participated. Results showed that object
      manipulation increased from baseline levels when experimenters prompted
      participants to manipulate leisure items, but that object manipulation was not
      maintained under unprompted conditions, and rates of SIB stayed within baseline
      levels. We then attempted to increase object manipulation further by (a)
      reinforcing object manipulation, (b) blocking SIB while reinforcing manipulation,
      and (c) preventing SIB by applying protective equipment while reinforcing object
      manipulation. Reinforcing object manipulation alone did not affect levels of
      object manipulation. Blocking effectively reduced attempts to engage in SIB for 1
      participant but produced no increase in object manipulation. When the 2nd
      participant was prevented from engaging in SIB through the use of protective
      equipment, rates of object manipulation increased dramatically but were not
      maintained when the equipment was removed. These results suggest that stimulation
      derived from object manipulation, even when supplemented with arbitrary
      reinforcement, may not compete with stimulation produced by stereotypic SIB;
      therefore, direct interventions to reduce SIB are required.

PMID- 10201104
TI  - An analysis of choice making in the assessment of young children with severe
      behavior problems.
AB  - We examined how positive and negative reinforcement influenced time allocation,
      occurrence of problem behavior, and completion of parent instructions during a
      concurrent choice assessment with 2 preschool-aged children who displayed severe
      problem behavior in their homes. The children were given a series of concurrent
      choice options that varied availability of parent attention, access to preferred
      toys, and presentation of parent instructions. The results showed that both
      children consistently allocated their time to choice areas that included parent
      attention when no instructions were presented. When parent attention choice areas
      included the presentation of instructions, the children displayed differential
      patterns of behavior that appeared to be influenced by the presence or absence of
      preferred toys. The results extended previous applications of reinforcer
      assessment procedures by analyzing the relative influence of both positive and
      negative reinforcement within a concurrent-operants paradigm.

PMID- 10201105
TI  - A case study of behavioral assessment and treatment of insect phobia.
AB  - We assessed the academic performance of a 14-year-old boy with insect phobia in
      the context of feared stimuli. The dependent measure was math calculation rate
      across three conditions that varied therapist statements about the presence of
      crickets and the actual presence of live crickets. Subsequent treatment consisted
      of graduated exposure and contingent rewards for math problem completion.
      Assessment results indicated that the boy's performance was consistently low in
      the presence of live crickets but not when he was spuriously informed that
      crickets were present (the primary referral concern). Treatment results indicated
      no effect from exposure alone and a dramatic effect when exposure was combined
      with contingent rewards.

PMID- 10201106
TI  - Clarifying an ambiguous functional analysis with matched and mismatched
      extinction procedures.
AB  - Results of functional analysis were ambiguous in suggesting that self-injurious
      behavior (SIB) was maintained by escape, sensory reinforcement, or both. To help
      clarify these results, we compared escape extinction, sensory extinction, and the
      combined treatments. Sensory extinction proved to be a necessary and sufficient
      treatment, whereas escape extinction failed to decrease SIB. These analyses
      helped to clarify the function of SIB and to identify an effective and efficient
      treatment.

PMID- 10201107
TI  - Decreasing signs of negative affect and correlated self-injury in an individual
      with mental retardation and mood disturbances.
AB  - We evaluated the effects of an enriched environment, based on a paired-choice
      preference assessment, on both rates of self-injurious behavior (SIB) and
      percentage of session intervals during which signs of negative affect were
      displayed by a woman with mental retardation and a mood disorder. Results
      suggested that SIB and signs of negative affect were highly correlated and that
      the enriched environment effectively reduced both.

PMID- 10201108
TI  - Examination of ambiguous stimulus preferences with duration-based measures.
AB  - Items that produced ambiguous results in an approach-based preference assessment
      were reassessed using a duration-based assessment. The reinforcing effects of
      three items on free-operant responding were subsequently tested. The results
      suggested that the duration-based assessment produced slightly more
      differentiated results and that predictions about reinforcer value, based on this
      assessment, were accurate.

PMID- 10201109
TI  - An expansion of the peer-tutoring paradigm: cross-age peer tutoring of social
      skills among socially rejected boys.
AB  - We examined the effects of a cross-age peer-tutoring program on the social skills
      of 2 sixth-grade and 2 kindergarten socially rejected and isolated boys. Peer
      tutoring consisted of the older boys conducting social skills training with their
      younger tutees. The frequency of positive social interactions increased for all 4
      boys, with maintenance of treatment gains following a 5-week interval.

PMID- 10201110
TI  - High performance flow injection analysis of recombinant protein G.
AB  - Chromatographic discs were investigated for their potential to substitute for the
      hitherto used cartridges in heterogeneous flow injection analysis. Originally
      designed for fast high performance liquid chromatography (HPLC) of biopolymers,
      the discs combine reliability with speed and resolution. This together with their
      price and their long-standing time made them attractive for use in flow injection
      analysis. The base material of the discs is a glycidyl methacrylate-co-ethylene
      dimethacrylate (GMA-EDMA) co-polymer. The epoxy groups inherent to this base
      structure can be used for immobilization purposes. In this first demonstration,
      antibodies were immobilized and the resulting affinity discs used for the fast
      analysis (< 5 min) of protein G from cell lysate of recombinant Escherichia coli.
      A linear calibration curve over several orders of magnitude as well as excellent
      reproducibility and correlation with data produced by conventional protein assay
      were obtained.

PMID- 10201111
TI  - Expression and purification of human interleukin-2 simplified as a fusion with
      green fluorescent protein in suspended Sf-9 insect cells.
AB  - A fusion protein of human interleukin-2 (hIL-2) and green fluorescent protein
      (GFP) was expressed in insect Sf-9 cells infected with recombinant baculovirus
      derived from the Autographa californica nuclear polyhedrosis virus (AcNPV). This
      fusion protein was comprised of a histidine affinity ligand for simplified
      purification using immobilized metal affinity chromatography (IMAC), UV-optimized
      GFP (GFPuv) as a marker, an enterokinase cleavage site for recovery of hIL-2 from
      the fusion, and the model product hIL-2. Successful production of hIL-2 as a
      fusion protein (approximately 52,000 Da) with GFPuv was obtained. GFPuv enabled
      rapid monitoring and quantification of the hIL-2 by simply checking the
      fluorescence, obviating the need for Western blot and/or ELISA assays during
      infection and production stages. There was no increased 'metabolic burden' due to
      the presence of GFPuv in the fusion product. The additional histidine residues at
      the N-terminus enabled efficient one-step purification of the fusion protein
      using IMAC. Additional advantages of GFP as a fusion marker were seen,
      particularly during separation and purification in that hIL-2 containing
      fractions were identified simply by illumination with UV light. Our results
      demonstrated that GFP was an effective non-invasive on-line marker for the
      expression and purification of heterologous protein in the suspended insect
      cell/baculovirus expression system.

PMID- 10201112
TI  - DNA sequence comparison considering both amino acid and nucleotide
      insertions/deletions because of evolution and experimental error.
AB  - Amino acid similarity often needs to be considered in DNA sequence comparison to
      elucidate gene functions. We propose a Smith-Waterman-like algorithm which
      considers amino acid similarity and insertions/deletions in sequences at the DNA
      level and at the protein level in a hybrid manner. The algorithm is applied to
      cDNA sequences of Oryza sativa and those of Arabidopsis thaliana. The results are
      compared with the results of application of NCBI's tblastx program (which
      compares the sequences in the BLAST manner after translation). It is shown that
      the present algorithm is very helpful in discovering nucleotide
      insertions/deletions originating from experimental errors as well as amino acid
      insertions/deletions due to evolutionary reasons.

PMID- 10201114
TI  - Parameters influencing human mu opioid receptor over-expression in baculovirus
      infected insect cells.
AB  - The cDNA encoding the human mu opioid receptor (hMOR) was cloned in the
      baculovirus Autographa californica (AcMNPV) under the control of the polyhedrin
      promoter. We investigated the influence of different molecular constructions on
      receptor expression levels: the receptor was fused either to an amino- or a
      carboxy-terminal histidine tag (hMOR-N-His and hMOR-C-His respectively), or to
      the cleavable sequence signal of the baculovirus gp64 glycoprotein (gp-hMOR and
      gp-hMOR-C-His). Two cell lines, Spodoptera frugiperda (Sf9) and Trichoplusia ni
      (BTI-TN-5B1-4), in combination with three different culture media were also
      tested for their ability to produce maximal protein expression. Molecular
      constructions and culture conditions were both shown to influence substantially
      protein production. The best results were obtained using cells adapted to serum
      free medium combined with constructions in fusion with the endogenous signal
      sequence of the baculovirus gp64 protein. Those conditions led to maximal
      expression and shortened the time required for receptor production. We also
      showed that an amino-terminal location of a hexahistidine tag was more
      detrimental to the expression level than a carboxy-terminal position.

PMID- 10201113
TI  - Manipulation of carbon assimilation with respect to expression of the pac gene
      for improving production of penicillin acylase in Escherichia coli.
AB  - A strategy of genetically manipulating carbon assimilation with respect to
      expression of the pac gene was employed for overproduction of recombinant
      penicillin acylase (PAC). Two expression plasmids of pCLL2902 and pCLL3201, which
      contain the pac coding region but differ in the pac regulatory region, were
      constructed for the production experiments. Expression of the pac gene was
      subjected to phenyl acetic acid (PAA-) induction and glucose catabolite
      repression for pCLL3201, whereas it was subjected to neither of the two
      transcriptional regulations for pCLL2902. The specific PAC activity for strains
      harboring pCLL2902 was significantly higher than that for strains harboring
      pCLL3201 due to an improved transcription efficiency. In addition, no inclusion
      bodies were observed upon production of PAC using the current expression systems.
      The results suggest that using the native pac promoter instead of a strong
      promoter such as tac for regulation is a feasible approach for production of PAC.
      The impact of the current expression systems is also significant from a process
      viewpoint since, using strains harboring pCLL2902, not only could glucose replace
      PAA as a carbon source of Escherichia coli cultures for production of PAC but
      also the volumetric PAC activity was highly improved.

PMID- 10201115
TI  - N-terminal methionine in recombinant proteins expressed in two different
      Escherichia coli strains.
AB  - Two genes coding for chloramphenicol acetyltransferase and human interferon
      gamma, respectively, were overexpressed constitutively in two different strains
      of Escherichia coli (E. coli LE392 and E. coli XL1). The N-terminal amino acid
      analysis of the purified proteins showed that: (a) the N-terminal methionine is
      processed more efficiently in E. coli LE392 rather than in E. coli XL1 cells; (b)
      the N-terminal methionine is removed better from the heterologous human
      interferon gamma in comparison with the homologous chloramphenicol
      acetyltransferase protein: and (c) there is no strong correlation between the
      efficiency of N-terminal procession and the yield of recombinant protein.

PMID- 10201116
TI  - Mechanical advantage of area of origin for the external pterygoid muscle in two
      murid rodents, Apodemus speciosus and Clethrionomys rufocanus.
AB  - The actions of masticatory muscles in relation to transverse grinding, associated
      with forward masticatory movement of the mandible, were investigated by using a
      mechanical model in the two murid rodents, the Japanese field mouse (Apodemus
      speciosus: subfamily Murinae) and the gray red-backed vole (Clethrionomys
      rufocanus: subfamily Arvicolinae). Furthermore, statics of the masticatory system
      on a sagittal plane while chewing is taking place were also analyzed in these
      rodents. The inward grinding movements of hemimandibles are generated by the
      posterior temporalis and internal and external pterygoids in both species. In
      addition to these muscles, the anterior temporalis also moves the hemimandibles
      lingually in Apodemus speciosus. The area of origin of the external pterygoid
      seems more advantageous for transverse grinding in A. speciosus than in
      Clethrionomys rufocanus. On the basis of the static analysis, the anterodorsal
      area of origin of the external pterygoid to the upper second and third molars in
      Clethrionomys rufocanus appears to be an adaptive character to prevent the jaw
      joints from dislocation during occlusion at a posterior point on the elongated
      row of cheek teeth.

PMID- 10201117
TI  - Growing new organs.

PMID- 10201118
TI  - Embryonic stem cells for medicine.

PMID- 10201119
TI  - Encapsulated cells as therapy.

PMID- 10201120
TI  - Tissue engineering: the challenges ahead.

PMID- 10201123
TI  - [Mollaret's meningitis].

PMID- 10201124
TI  - [Herpes simplex encephalitis, Japanese encephalitis, cytomegalovirus
      encephalitis].

PMID- 10201122
TI  - [Lymphocytic choriomeningitis].

PMID- 10201125
TI  - [Varicella and herpes zoster encephalitis].

PMID- 10201126
TI  - [Epstein-Barr virus encephalitis].

PMID- 10201121
TI  - [Enteroviral meningitis].

PMID- 10201127
TI  - [Postinfectious encephalitis].

PMID- 10201129
TI  - [Progressive rubella panencephalitis].

PMID- 10201128
TI  - [Acute rubella encephalitis].

PMID- 10201130
TI  - [Other viral encephalitis].

PMID- 10201131
TI  - [HTLV-I-associated myelopathy].

PMID- 10201132
TI  - [Myelitis].

PMID- 10201133
TI  - [Myeloradiculitis].

PMID- 10201134
TI  - [Radiculomyelopathy due to genital herpes simplex virus infection (Elsberg
      syndrome)].

PMID- 10201135
TI  - [Ramsay Hunt syndrome].

PMID- 10201136
TI  - [Subacute sclerosing panencephalitis (SSPE)].

PMID- 10201137
TI  - [Immunosuppressive measles encephalitis].

PMID- 10201138
TI  - [Progressive multifocal leukoencephalopathy].

PMID- 10201139
TI  - [Viral myocarditis].

PMID- 10201140
TI  - [Viral pericarditis].

PMID- 10201141
TI  - [Viral pleuritis].

PMID- 10201142
TI  - [Croup].

PMID- 10201143
TI  - [Influenza virus pneumonia].

PMID- 10201144
TI  - [Cytomegalovirus pneumonia].

PMID- 10201145
TI  - [Rhinovirus pneumonia].

PMID- 10201146
TI  - [Adenoviral pneumonia].

PMID- 10201147
TI  - [Varicella pneumonia].

PMID- 10201148
TI  - [Measles pneumonia].

PMID- 10201149
TI  - [Hepatitis A].

PMID- 10201150
TI  - [Hepatitis B].

PMID- 10201151
TI  - [Hepatitis F].

PMID- 10201152
TI  - [Adenoviral hepatitis].

PMID- 10201153
TI  - [Hepatitis associated with HIV].

PMID- 10201154
TI  - [Herpes simplex virus hepatitis].

PMID- 10201155
TI  - [Cytomegalovirus hepatitis].

PMID- 10201156
TI  - [EB virus hepatitis].

PMID- 10201157
TI  - [Sporadic non-bacterial gastroenteritis].

PMID- 10201158
TI  - [Herpes zoster].

PMID- 10201159
TI  - [Gianotti-Crosti syndrome and Gianotti disease].

PMID- 10201160
TI  - [Smallpox].

PMID- 10201161
TI  - [Acute hemorrhagic conjunctivitis].

PMID- 10201162
TI  - [Epidemic pleurodynia].

PMID- 10201163
TI  - [Hemorrhagic cystitis (adenovirus infection)].

PMID- 10201164
TI  - [Aplastic crisis (human parvovirus B19 infection)].

PMID- 10201165
TI  - [X-linked lymphoproliferative (XLP) syndrome (Duncan disease)].

PMID- 10201166
TI  - [Chronic fatigue syndrome].

PMID- 10201167
TI  - [Virus-associated hemophagocytic syndrome].

PMID- 10201168
TI  - [Miliary tuberculosis].

PMID- 10201169
TI  - [Tuberculous meningitis].

PMID- 10201170
TI  - [Intracranial tuberculoma].

PMID- 10201171
TI  - [Tuberculosis of the spine--surgical treatment].

PMID- 10201172
TI  - [Pulmonary tuberculosis].

PMID- 10201173
TI  - [Tuberculous hilar lymphadenopathy].

PMID- 10201174
TI  - [Tuberculosis pleurisy].

PMID- 10201175
TI  - [Tuberculous pericarditis].

PMID- 10201176
TI  - [Intestinal tuberculosis].

PMID- 10201177
TI  - [Urinary tuberculosis].

PMID- 10201178
TI  - [Cervical tuberculous lymphadenitis].

PMID- 10201179
TI  - [Osteoarticular tuberculosis with emphasis on tuberculous spondylitis].

PMID- 10201180
TI  - [Non-tuberculous mycobacteriosis].

PMID- 10201181
TI  - [Hansen's disease, leprosy].

PMID- 10201182
TI  - [Psittacosis].

PMID- 10201183
TI  - [Chlamydia trachomatis pneumonia].

PMID- 10201184
TI  - [Trachoma].

PMID- 10201185
TI  - [Chlamydia pneumoniae pneumonia].

PMID- 10201186
TI  - [Mycoplasma pneumonia].

PMID- 10201187
TI  - [Endocarditis and myocarditis caused by Mycoplasma].

PMID- 10201188
TI  - [Acute Q fever].

PMID- 10201189
TI  - [Chronic Q fever].

PMID- 10201191
TI  - [Rocky Mountain spotted fever].

PMID- 10201190
TI  - [Spotted fever group rickettsiosis: introduction].

PMID- 10201192
TI  - [Japanese spotted fever].

PMID- 10201193
TI  - [Rickettsialpox].

PMID- 10201194
TI  - [Queensland tick typhus, and other SFG rickettsiosis].

PMID- 10201195
TI  - [African tick-bite fever].

PMID- 10201196
TI  - [Boutonneuse fever].

PMID- 10201197
TI  - [Murine typhus].

PMID- 10201198
TI  - [Brill-Zinsser disease].

PMID- 10201199
TI  - [Epidemic typhus].

PMID- 10201200
TI  - [Sennetsu rickettsiosis].

PMID- 10201201
TI  - [Classic type tsutsugamushi disease].

PMID- 10201202
TI  - [New type tsutsugamushi disease].

PMID- 10201203
TI  - [Trench fever].

PMID- 10201204
TI  - [Relapsing fever].

PMID- 10201205
TI  - [Leptospirosis (Weil's disease)].

PMID- 10201206
TI  - [Rat-bite fever].

PMID- 10201207
TI  - [Systemic aspergillosis].

PMID- 10201208
TI  - [Cerebral aspergillosis].

PMID- 10201209
TI  - [Pulmonary aspergilloma].

PMID- 10201210
TI  - [Invasive pulmonary aspergillosis].

PMID- 10201211
TI  - [Non-invasive pulmonary aspergillosis].

PMID- 10201212
TI  - [Allergic bronchopulmonary aspergillosis].

PMID- 10201213
TI  - [Hepatic aspergillosis].

PMID- 10201214
TI  - [Systemic (disseminated) candidiasis (candidosis)].

PMID- 10201215
TI  - [Candidal meningitis].

PMID- 10201217
TI  - [Pulmonary candidiasis].

PMID- 10201216
TI  - [Candida endocarditis].

PMID- 10201218
TI  - [Hepatic candidiasis].

PMID- 10201219
TI  - [Esophageal candidiasis].

PMID- 10201220
TI  - [Candida urinary tract infection].

PMID- 10201221
TI  - [Disseminated cryptococcosis].

PMID- 10201222
TI  - [Central nervous system cryptococcosis].

PMID- 10201223
TI  - [Pulmonary cryptococcosis].

PMID- 10201224
TI  - [Hepatic cryptococcosis].

PMID- 10201225
TI  - [Cryptococcal prostatitis].

PMID- 10201226
TI  - [Rhinocerebral mucormycosis and systemic mucormycosis].

PMID- 10201227
TI  - [Progressive disseminated histoplasmosis].

PMID- 10201228
TI  - [Pulmonary histoplasmosis].

PMID- 10201229
TI  - [Coccidioidomycosis].

PMID- 10201230
TI  - [Sporotrichosis].

PMID- 10201231
TI  - [Chromomycosis].

PMID- 10201232
TI  - [Allescheriasis].

PMID- 10201233
TI  - [Summer-type hypersensitivity pneumonitis].

PMID- 10201234
TI  - [Disseminated trichosporonosis].

PMID- 10201235
TI  - [Blastomycosis].

PMID- 10201236
TI  - [Geotrichosis].

PMID- 10201237
TI  - [Cutaneous (skin) candidiasis (candidosis)].

PMID- 10201238
TI  - [Oral candidiasis (candidosis) (thrush)].

PMID- 10201239
TI  - [Tinea pedis].

PMID- 10201240
TI  - [Trypanosomiasis].

PMID- 10201241
TI  - [Pneumocystis carinii pneumonia].

PMID- 10201242
TI  - [Primary amebic meningoencephalitis (Naegleria)].

PMID- 10201243
TI  - [Granulomatous amebic encephalitis (Acanthameba spp)].

PMID- 10201244
TI  - [Amoebic liver abscess].

PMID- 10201245
TI  - [Amoebic dysentery].

PMID- 10201246
TI  - [Giardiasis].

PMID- 10201247
TI  - [Isosporiasis (Isospora belli)].

PMID- 10201248
TI  - [Balantidiosis coli].

PMID- 10201249
TI  - [Wakana disease].

PMID- 10201250
TI  - [Creeping eruption].

PMID- 10201251
TI  - [Pulmonary strongyloidiasis].

PMID- 10201252
TI  - [Pinworm infection (enterobiasis)].

PMID- 10201253
TI  - [Ascariasis].

PMID- 10201254
TI  - [Bancrofitian filariasis, Malayan filariasis].

PMID- 10201255
TI  - [Onchocerciasis].

PMID- 10201256
TI  - [Gnathostomiasis].

PMID- 10201257
TI  - [Gastric anisakiasis].

PMID- 10201258
TI  - [Intestinal anisakiasis].

PMID- 10201259
TI  - [Trichinosis; trichinellosis].

PMID- 10201260
TI  - [Trichuriasis].

PMID- 10201261
TI  - [Trichostrongyliasis].

PMID- 10201262
TI  - [Angiostrongyliasis].

PMID- 10201263
TI  - [Cerebral schistosomiasis].

PMID- 10201264
TI  - [Schistosomiasis (intestinal, hepatic, urinary tract)].

PMID- 10201265
TI  - [Paragonimiasis westermani].

PMID- 10201266
TI  - [Paragonimiasis miyazakii].

PMID- 10201267
TI  - [Clonorchiasis].

PMID- 10201268
TI  - [Metagonimiasis yokogawai].

PMID- 10201269
TI  - [Fascioliasis].

PMID- 10201270
TI  - [Tapeworm infections].

PMID- 10201271
TI  - [Neurocysticercosis].

PMID- 10201272
TI  - [Ectoparasitic diseases and acari borne diseases].

PMID- 10201273
TI  - [Scabies].

PMID- 10201274
TI  - A look back: the foundations of anatomy.

PMID- 10201275
TI  - Alternative therapies resources.

PMID- 10201276
TI  - Graduate nursing programs offering emergency or trauma-related nursing tracks.

PMID- 10201278
TI  - Different effect of desipramine on protein kinase C in platelets between bipolar
      and major depressive disorders.
AB  - Protein kinase C (PKC) activity was investigated in platelets from affective
      disorder subjects and healthy volunteers. The PKC activity of platelets incubated
      with desipramine was determined in vitro. The PKC activity of the major
      depressive disorder subjects and healthy volunteers was inhibited by desipramine,
      whereas that of the bipolar disorder subjects showed both inhibition and
      activation. In addition, the base PKC activity incubation with antidepressants of
      the major depressive disorder patients was significantly higher than of the
      bipolar disorder patients. These preliminary results suggest that the function of
      PKC may, at least in part, be associated with the mechanism of affective
      disorder.

PMID- 10201277
TI  - Recent advances in dementia research in Japan: Alzheimer-type dementia.
AB  - In a previous article, recent reports by Japanese researchers on non-Alzheimer
      type degenerative dementias were reviewed. In the present article, recent
      Japanese reports on Alzheimer-type dementia (ATD) are reviewed. Alzheimer-type
      dementia has received great attention and has been studied from various
      viewpoints in Japan as well as in Europe and the Americas. In Japan, although it
      was believed that vascular dementia was the most frequent dementia in the
      elderly, ATD has recently been shown to be the most predominant type of dementia.
      Such a great number of papers on ATD have been reported in Japan that mainly the
      clinical, neuropathological, biochemical and molecular biological research papers
      alone are reviewed here.

PMID- 10201279
TI  - Effects of three principal constituents in chewing gum on electroencephalographic
      activity.
AB  - The effects of three principal constituents (sugar, spearmint, and gumbase) in
      chewing gum on EEG findings in 20 normal subjects were investigated. After they
      chewed the gumbase, theta activity decreased significantly at Fp2, O1, T3, T4,
      F4, P3, and Pz; alpha activity increased significantly at O1 and decreased
      significantly at Fpl, and beta activity increased significantly at Fpl, Fp2, O1,
      T3, T4, P3 and Pz. After they inhaled the spearmint, alpha activity decreased
      significantly at 02, F3, P4, and Fz, and beta increased significantly at 02, F3,
      P4, and Fz. The mean frequency of the alpha band was significantly higher than
      after 1 min at rest without inhalation. After the subjects chewed the gumbase
      with sucrose, theta activity increased at Fp2 and Fz; alpha activity increased
      significantly at T3; and beta activity decreased significantly at Fpl, Fp2, F4,
      P3, P4, Fz, and Pz. The mean frequency of the alpha band was significantly lower
      than after 1 min at rest without it at almost all the positions. These results
      suggest that the gumbase with sucrose induced relaxed concentration effects while
      inhalation of spearmint induced arousal effects. The chewing of gumbase showed
      arousal tendency.

PMID- 10201280
TI  - Methodological issues of an epidemiological study: from the results of a study on
      psychological problems seen in outpatients visiting the internal medicine
      departments of general hospitals.
AB  - The frequency and type of psychological problems of outpatients in general
      healthcare settings, the recognition and management of those problems by
      physicians, and the course of the problems were investigated using a two-stage
      sampling design method. The subjects were outpatients visiting the department of
      internal medicine of two general hospitals in Nagasaki prefecture. For the first
      stage investigation, the General Health Questionnaire 12-item version (GHQ-12)
      was used. A second-stage investigation was then conducted, which used many
      instruments containing the Composite International Diagnostic Interview (CIDI)
      and Groningen Social Disability Scale (GSDS). As a result, 1555 patients
      participated in the first-stage, 483 were selected and 336 (69.5%) participated
      in the second-stage investigation. No significant differences were seen in age or
      sex between the GHQ score groups among the 1555 subjects of the core sample. The
      background factors of the two hospital samples differed significantly in the
      distribution of age, sex and physical diseases. There were some differences in
      the participation between men and women in age and GHQ score. It was then
      suggested that variances should be considered in such an epidemiological study.

PMID- 10201281
TI  - Rapid transcranial magnetic stimulation and normalization of the dexamethasone
      suppression test.
AB  - Non-suppression of post-dexamethasone cortisol is a feature of
      endogenous/melancholic depression. Normalization of the dexamethasone suppresion
      test (DST) response is a feature of remission and antidepressant treatment.
      Twelve consecutive depressed non-suppressers were treated with rapid transcranial
      magnetic stimulation (rTMS). Six demonstrated normalization and good clinical
      improvement which was sustained for at least 1 month. Thus, rTMS has some
      biological effects in common with other antidepressant treatments.

PMID- 10201282
TI  - Screening of vascular cognitive impairment on a Hungarian cohort.
AB  - Cerebrovascular disease is a major public health problem in Eastern European
      countries. A Hungarian post-stroke population was examined to estimate the rate
      of dementia, the risk factors for cognitive impairment, and the applicability of
      a recently established Canadian diagnostic checklist in this cohort. Chronic
      cerebrovascular outpatients were screened for cognitive impairment with a
      combined checklist: the Diagnostic Checklist for Vascular Dementia established by
      the Consortium of Canadian Centres for Clinical Cognitive Research using the Mini
      Mental State Examination instead of the detailed neuropsychological part of the
      Checklist. Of the 247 consecutive patients at a cerebrovascular outpatient unit,
      176 had cerebrovascular disorder diagnosed either by computed tomography (CT;
      n=126) or by the clinical signs. Of these, 15% were cognitively impaired and 5%
      fulfilled the criteria of dementia. The mean age of the patients with cognitive
      impairment was significantly higher than that of patients with normal cognition
      (68.2+/-10.2 and 60.5+/-10.5 years, P<0.001). The Barthel index was significantly
      lower in the cognitively affected group than in non-affected patients (92.4+/
      16.0 and 97.1+/-8.7, P=0.027). Diabetes and more than two subcortical infarcts on
      CT or magnetic resonance imaging were more frequent in patients with cognitive
      loss (P=0.043 and P=0.013, respectively). Cognitive performance was also
      influenced by the level of education. Higher age, diabetes, motor deficits, and
      multiple subcortical infarcts are risk factors for cognitive impairment after
      stroke. The combined checklist appears to be a practical screening test for
      cognitive impairment in patients with chronic cerebrovascular diseases.

PMID- 10201283
TI  - Misinterpretation of facial expression: a cross-cultural study.
AB  - Accurately recognizing facial emotional expressions is important in psychiatrist
      versus-patient interactions. This might be difficult when the physician and
      patients are from different cultures. More than two decades of research on facial
      expressions have documented the universality of the emotions of anger, contempt,
      disgust, fear, happiness, sadness, and surprise. In contrast, some research data
      supported the concept that there are significant cultural differences in the
      judgment of emotion. In this pilot study, the recognition of emotional facial
      expressions in 123 Japanese subjects was evaluated using the Japanese and
      Caucasian Facial Expression of Emotion (JACFEE) photos. The results indicated
      that Japanese subjects experienced difficulties in recognizing some emotional
      facial expressions and misunderstood others as depicted by the posers, when
      compared to previous studies using American subjects. Interestingly, the sex and
      cultural background of the poser did not appear to influence the accuracy of
      recognition. The data suggest that in this young Japanese sample, judgment of
      certain emotional facial expressions was significantly different from the
      Americans. Further exploration in this area is warranted due to its importance in
      cross-cultural clinician-patient interactions.

PMID- 10201284
TI  - An autopsy case of myotonic dystrophy with mental disorders and various
      neuropathologic features.
AB  - An autopsy case of myotonic dystrophy (MD) is reported. The patient was a 58-year
      old male. He presented with muscular weakness and muscular atrophy at the age of
      33 and was diagnosed as having MD from myotonic symptoms (i.e. percussion and
      grip myotonia) at 49 years old. Mental disorders including a delusional
      hallucinatory state, mental slowness, indifference, and lack of spontaneity as
      well as visual cognitive impairments were noted at the age of 55. He showed
      Parkinsonism and died of septic shock. T2-weighted magnetic resonance imaging
      demonstrated diffuse cortical atrophy with a marked frontal atrophy and high
      intensity signals in the white matter. Single photon emission computed tomography
      demonstrated hypoperfusion in the frontal cortex. Neuropathologic observation
      revealed neuronal loss in the superficial layer of the frontal and parietal
      cortices and extensive neuronal loss in the occipital cortex, intracytoplasmic
      inclusion body in the nerve cell of the medial thalamic nuclei, neuronal loss and
      presence of Lewy bodies in the substantia nigra and locus ceruleus corresponding
      to the pathologic features of Parkinson's disease, as well as abnormalities of
      myelin in the white matter. The present case suggests that in MD brain, various
      neuropathologic changes may occur and they contribute to the mental disorders.

PMID- 10201285
TI  - Reliability of childhood mental disorder: diagnoses by Japanese psychologists.
AB  - The recent entry of psychologists into psychiatric practices and schools in Japan
      calls for diagnostic skills, because psychiatrists are less available in such
      settings. We examined the reliability of the diagnoses of 10 DSM-IV childhood
      mental disorders by 11 Japanese psychologists, using 20 case vignettes. Most
      categories had good reliability (kappa), except for attention deficit
      hyperactivity disorder. Japanese clinical psychologists may be able to use DSM-IV
      reliably as a tool for diagnosis of childhood psychiatric disorders, if
      sufficient training is provided.

PMID- 10201286
TI  - Catatonic features: differential diagnosis and treatments at an emergency unit.
AB  - During a 2-year period, 34 patients of catatonic features in Chinese ethnic
      background Taiwanese were brought to the emergency unit of Chang Gung Memorial
      Hospital at Linkou. The ratios of the causes of catatonic features by
      schizophrenic disorders, mood disorders, neuroleptic-induced disorders, and
      general medical conditions were 26, 9, 24 and 41%, respectively. After the
      treatments of antipsychotics, benzodiazepam, or electroconvulsive therapy (ECT),
      24 patients (70.6%) showed complete remission, seven patients (20.6%) showed
      partial remission, and three patients (8.8%) showed no response (two died).
      Additionally, a suggestive period is proposed in order to distinguish acute and
      insidious onset catatonic conditions to help clinicians in deciding on
      probability immediately. The patients were grouped into four diagnostic
      categories; namely, schizophrenic disorders, mood disorders, neuroleptic-induced
      disorders, and general medical conditions for comparison. One-way ANOVA and
      Duncan's multiple-range test were used for continuous variables, and the Chi
      squared test was used for categorical variables. The mean duration of 'insidious
      onset catatonic condition' (including schizophrenic disorders and general medical
      conditions) before seeking medical help was longer than 3.33 weeks, while the
      mean duration of 'acute catatonic condition' (including mood disorders and
      neuroleptic-induced disorders) was shorter than 1.83 weeks. These findings
      suggest that 2-3 weeks would be a cut-off point for acute or insidious onsets of
      catatonic conditions.

PMID- 10201288
TI  - Considerations on the vicissitudes of unconscious guilt feelings from pre
      adolescence to early adolescence.
AB  - The author describes re-edition of the rapprochement subphase (the early period
      of the second individuation process) occurring from pre-adolescence to early
      adolescence by means of case presentation. Factors that motivate youngsters to
      become aware of unconscious guilt in their inner world are discussed in the
      course of this study. In the pre-adolescent period youngsters begin to develop a
      conscious guilt more like that of an adult. Under the service of ego, a child
      modulates from a primitive externalized unconscious guilt conditioned by
      emotional exchanges with their parents to a more evolved state of self-awareness.
      Furthermore, it is possible that changes from externalization of unconscious
      guilt to guilt with which the ego is directly concerned, (that is, internalized
      guilt), will resolve the infantile relationship that young adolescents have had
      with their parents and play an important role in developing social independence.

PMID- 10201287
TI  - A case of West syndrome well controlled by very short and low-dose ACTH therapy.
AB  - The case of a 5-month-old boy with tuberous sclerosis and West syndrome is
      reported. Tonic spasms were noted from the age of 4 months. High-dose pyridoxal
      phosphate could not control the seizures completely. Very short and low-dose
      adrenocorticotropic hormone (ACTH) therapy (i.e. 0.011 mg/kg per dose, 12 times
      in 20 days) controlled the seizures, while pyridoxal phosphate was on. Early
      tapering of ACTH was successfully done while abnormal electroencephalogram (EEG)
      findings remained. Although side effects such as hypertension and brain shrinkage
      were transiently observed, both the cognitive and seizure prognoses were
      excellent at the age of 3 years and 2 months. The good response to a small dosage
      of ACTH might be due to some responsiveness of the high-dose pyridoxal phosphate
      and the underlying cause of tuberous sclerosis with normal development before
      onset. The present case illustrates that the duration and dosage of ACTH therapy
      in West syndrome should be modified according to the individual's requirements.

PMID- 10201289
TI  - Demonstration of ganglioside GD3 in human reactive astrocytes.
AB  - Astrocytes are the cells that actively participate in the process of lesion
      repair in the central nervous system (CNS), and reactive astrocytosis of varying
      degrees becomes apparent with time in any pathological condition occurring in the
      normally developed postnatal CNS. Ganglioside GD3 (II3a(NeuAca2-8NeuAc)-LacCer,
      GD3) in reactive astrocytes from autopsied patients with Creutzfeldt-Jakob
      disease (CJD) and old cerebral infarction was investigated immunocytochemically,
      using mouse IgM anti-GD3 monoclonal antibody (DSG-1). Reactive astrocytes in CJD
      and cerebral infarction demonstrated GD3-immunoreactivity within the cytoplasm.
      Normal astrocytes were negative. The present data raise the possibility that GD3
      in reactive astrocytes has biological implications for the properties of the
      cells, such as cellular motility.

PMID- 10201290
TI  - The Noh mask test for analysis of recognition of facial expression.
AB  - A preliminary study on the Noh mask test for analysis of recognition of facial
      expression was performed. The present study was conducted on 15 normal subjects
      (mean age: 32 years, SD 9.7 years) as the first step to test for the differences
      between psychiatric patients and normal subjects. Stimuli were created by
      photographs of 15 Noh masks at different vertical angles. Subjects were given 12
      tasks (12 emotion items), and each task consisted of 15 trials (15 Noh mask
      images). In each trial, the subject viewed a colour monitor, and was shown an
      emotion item, followed by a Noh mask image. The subject pressed either the yes or
      no key to indicate whether the Noh mask image expressed the emotion item. The
      subject's response and reaction time to each Noh mask image showed no deviation,
      although the subject's response and reaction time to each emotion item showed
      some deviation. As the vertical angle of the Noh mask changed, normal subjects
      recognized all emotion items except the 'uncanny' expression. Factor analysis of
      the 15 Noh mask images produced three factors, and the analysis of 12 emotion
      items produced five factors. Thus, the Noh mask test was simplified to nine
      images and nine items. Further developments of the Noh mask test may include the
      evaluation of the dysfunction of perception on delicate facial expression in
      psychiatric patients.

PMID- 10201291
TI  - Panic attacks in patients with chronic schizophrenia: a complication of long-term
      neuroleptic treatment.
AB  - Panic attacks meeting the diagnostic criteria for panic disorder (DSM-III-R) were
      found in nine (20%) of 45 patients suffering chronic schizophrenia for more than
      5 years. The scores of the Hamilton Depression Rating Scale and the Simpson Angus
      Scale were significantly higher in the group of patients with panic attacks. They
      also tended to be taking neuroleptics in larger doses than in the other group.
      The present report suggests that long-term treatment with neuroleptics is closely
      related to the manifestation of panic attacks in chronic schizophrenia. It also
      suggests that when panic attacks are seen frequently in patients taking high
      doses of neuroleptics, dose reduction of neuroleptics should be considered.

PMID- 10201293
TI  - Current results of the surgical management of aneurysms of the basilar apex.
AB  - OBJECTIVE: To provide current information regarding the expected clinical
      outcomes and sources of morbidity and mortality in the modern surgical management
      of basilar apex aneurysms. METHOD: A retrospective review was conducted of 303
      cases of such aneurysms that were treated surgically during 18 years at one
      institution. Postoperative angiography was performed in 81% of the cases.
      Clinical grading using the Glasgow Outcome Scale was conducted at the time of
      hospital discharge and for 91% of the surviving patients at 6 months after
      surgery. The preoperative parameters that were linked statistically to poor
      clinical outcome were identified through the use of single and multivariate
      analyses. RESULTS: More than 80% of the patients were operated on using some
      modification of the trans-sylvian exposure, and temporary arterial occlusion was
      used routinely. Good outcomes (Glasgow Outcome Scale scores of 4 or 5) were
      achieved in 76% of the patients at the time of discharge and in 81% of the
      patients at 6 months after surgery. There was no incidence of postoperative
      subarachnoid hemorrhage. Residual aneurysm was revealed by postoperative
      angiography in 6% of the cases. Factors found to be statistically linked to poor
      outcome included poor admission grade (Hunt and Hess Grades IV and V), patient
      age older than 65 years, computed tomographic demonstration of thick basal
      cistern clot, aneurysm size greater than 20 mm, and symptoms attributable to
      brain stem compression. CONCLUSION: Direct microsurgical repair of basilar apex
      aneurysms should result in good clinical outcomes in 80 to 85% of cases, with
      reliable prevention of subarachnoid bleeding and routine elimination/reduction of
      symptoms secondary to mass effect. Those patients who are at high risk for poor
      outcomes can be identified by the presence of certain clinical, radiographic, and
      demographic features before undergoing surgery and can be considered for
      alternative or adjunctive modes of therapy if long-term efficacy of such
      treatment is demonstrated.

PMID- 10201292
TI  - Direct and buffering effects of social support on depressive symptoms of the
      elderly with home help.
AB  - The purpose of the present study was to examine the prevalence of depressive
      symptoms on the Center for Epidemiologic Studies Depression Scale (CES-D) and the
      effect of life stressors or social support on depressive symptoms in 303 elderly
      people receiving social services at home. We conducted a questionnaire survey six
      times with a 1-month interval. In the initial wave of questionnaires, 92 (31%)
      scored 16 points or above on the CES-D, indicative of a risk for depression.
      Before life stressors, subjects with low-level support showed significantly more
      severe depressive symptoms than those with high-level support. Subjects with low
      level support were significantly more depressive after life stressors than they
      had been before, whereas those with middle- and high-level support showed no such
      difference. The former and latter results seem to suggest the direct and
      buffering effects of social support on depressive symptoms, respectively.

PMID- 10201294
TI  - Oculomotor nerve palsy after surgery for upper basilar artery aneurysms.
AB  - OBJECTIVE: The goals of this study were to evaluate the relationship between
      postoperative oculomotor nerve palsy and other clinical factors and to improve
      preoperative estimations of the risk. Such an evaluation has not been previously
      described in the literature. METHODS: Patient records for 77 basilar tip aneurysm
      cases and 28 basilar superior cerebellar artery aneurysm cases treated between
      1981 and 1997 were reviewed. Clinical and radiological parameters were separately
      analyzed using the chi2 test, and then multiple-regression analysis was used.
      RESULTS: Postoperative oculomotor palsy occurred in 25 (32%) patients with
      basilar tip aneurysms and 11 (39%) patients with basilar superior cerebellar
      artery aneurysms, in addition to 2 patients with basilar tip aneurysms and 3
      patients with basilar superior cerebellar artery aneurysms who exhibited
      oculomotor palsy before surgery. For both type of aneurysms, the size and
      direction of the aneurysms were closely related to oculomotor nerve palsy. The
      complication also tended to occur in early surgery cases, in younger patients,
      and in patients of poor-clinical grade status. CONCLUSION: In this study, some
      clinical and radiological factors were found to be associated with postoperative
      oculomotor nerve palsy.

PMID- 10201295
TI  - Aneurysm retreatment after Guglielmi detachable coil and nondetachable coil
      embolization: report of nine cases and review of the literature.
AB  - OBJECTIVE: Guglielmi detachable coil embolization of cerebral aneurysms is
      becoming increasingly used to manage certain intracranial lesions based on
      aneurysm geometry, patient condition, and patient and surgeon preferences.
      Aneurysm recurrences or incomplete initial treatments are not uncommon, making
      repeat treatment necessary using either surgical or endovascular techniques.
      METHODS: Between January 1993 and June 1998, 1025 cerebral aneurysms were managed
      by the authors at a single hospital. One hundred twenty-four of these lesions
      were treated using Guglielmi detachable coils, and one was managed with
      nondetachable coils. During the follow-up period, eight patients who underwent
      embolization at our institution and one who underwent embolization elsewhere
      received repeat treatment. Five were approached surgically, and four underwent re
      embolization. All charts and films were reviewed retrospectively to determine
      patient outcome and clinical success. RESULTS: No patient in the subgroup of this
      clinical study suffered a permanent complication from initial aneurysm coiling,
      no episodes of subsequent bleeding occurred, and no complications resulted from
      any subsequent therapies. The anatomic results were excellent, and all aneurysms
      were totally or near totally obliterated. CONCLUSION: Subtotal initial coil
      embolization of aneurysms can be managed safely using a variety of surgical and
      endovascular techniques. Our approach to this predicament, lessons we have
      learned, and a review of the literature are herein discussed.

PMID- 10201296
TI  - Supratentorial ependymomas in adult patients.
AB  - OBJECTIVE: Ependymomas arise from different areas in the neuraxis and have
      variable outcomes that depend on tumor location and patient age at the time of
      presentation. The predictive value of histology for these tumors is unresolved.
      We report a series of adult patients with supratentorial ependymomas to
      characterize the roles of surgery, histology, ploidy, and proliferation index in
      tumor control. METHODS: Fourteen of the 23 supratentorial ependymomas were in the
      region of the third ventricle and the remainder were located in the hemispheres.
      Resections were gross total in 12 patients, subtotal in 8, and biopsy in 3. A
      single pathologist reviewed all slides and quantitated the deoxyribonucleic acid.
      The mean follow-up duration was 95 months (+/-75 mo). RESULTS: All of the
      malignant ependymomas were hemispheric (n = 4). Mortality occurred only in
      patients with third ventricular tumors; two patients died as a result of surgical
      complications and three as a result of tumor progression. Kaplan-Meier estimates
      of 5- and 10-year survival rates were 100% for hemispheric and 72.5% for third
      ventricular tumors (62.5% including the two perioperative deaths). The median
      time to recurrence was 53 months, with a 10-year progression-free survival rate
      of 27%. Univariate analysis revealed that recurrence was associated with
      malignant histology, including mitoses, cellularity, and aneuploidy. For
      nonmalignant ependymomas, recurrence was associated with subtotal resection and
      metastases. S-phase fraction did not correlate with recurrence. Only malignant
      histology correlated with recurrence on multivariate analysis. CONCLUSION:
      Although the numbers are too small to draw any definite conclusions, treatment of
      ependymomas that arise in the supratentorial compartment in adult patients
      results in excellent outcomes despite frequent recurrences. Association with the
      third ventricle and metastases seem to have a negative impact on survival,
      whereas malignant histology, subtotal resection, and metastases may be predictors
      of recurrence.

PMID- 10201297
TI  - Vascular endothelial growth factor expression, vascular volume, and, capillary
      permeability in human brain tumors.
AB  - OBJECTIVE: Vascular endothelial growth factor (VEGF) is an endothelial cell
      specific mitogen and a potent inducer of vascular permeability. In this study, we
      determined whether expression of VEGF is correlated with in vivo measurements of
      the capillary permeability and vascular volume of primary human brain tumors.
      METHODS: Tumor samples (seven glioblastomas, one anaplastic astrocytoma, two low
      grade astrocytomas, one pilocytic astrocytoma, and three primary cerebral
      lymphomas) were stereotactically obtained from 14 patients. A semiquantitative
      polymerase chain reaction was used to quantify the relative expression of VEGF
      messenger ribonucleic acid in the tumors. VEGF protein was demonstrated in tissue
      sections by immunohistochemical techniques. A two-compartment dynamic computed
      tomographic method was used to quantitatively measure the aforementioned
      parameters in the regions from which the biopsies were obtained. RESULTS: In
      glial tumors, there was significant correlation of VEGF messenger ribonucleic
      acid levels with capillary permeability (P < 0.05) and vascular volume (P <
      0.01). Although all primary cerebral lymphomas showed considerable increases in
      capillary permeability and vascular volume, VEGF expression was only slightly
      upregulated in these tumors. CONCLUSION: Our findings are consistent with the
      hypothesis that VEGF may be responsible for endothelial cell proliferation and
      vascular permeability in glial tumors. This relationship has implications for
      clinical applications, i.e., assessment of delivery of water-soluble drugs,
      treatment of edema, and antiangiogenesis therapy based on inhibition of VEGF
      function.

PMID- 10201298
TI  - Hyperostosis associated with meningioma of the cranial base: secondary changes or
      tumor invasion.
AB  - OBJECTIVE: Hyperostosis associated with intracranial meningiomas is a well
      described entity. The cause, management, and prognosis of these bony changes have
      long been a point of controversy. Some authors have postulated that hyperostotic
      changes are secondary to the formation of the tumor and do not constitute
      invasion of the tumor into the bone. Determining this point has direct
      implications in the treatment of these patients, especially regarding surgical
      considerations. To more thoroughly evaluate this question, a study correlating
      the morphology to the radiology is necessary. METHODS: In this study, 51 patients
      underwent resection for meningiomas involving the cranial base. Preoperative
      radiographic evaluation using magnetic resonance imaging and/or computed
      tomography was performed, and areas of hyperostosis were identified. During the
      resection of the tumor, biopsies from these hyperostotic regions were sent for
      histological evaluation regarding the presence or absence of tumor invasion of
      the bone. RESULTS: Preoperative neuroradiological assessment identified 26
      patients with radiographic evidence of hyperostosis. Histological examination of
      the resected bone showed tumor invasion in 35 patients, including the area of
      radiographically identified hyperostosis in 25 of the 26 patients. The floor of
      the middle fossa was a specific area of low sensitivity for preoperative
      assessment of associated hyperostosis. CONCLUSION: These results indicate that
      hyperostosis associated with meningiomas involving the cranial base are caused by
      tumor invasion of the bone histologically.

PMID- 10201299
TI  - Cranial extradural empyema in the era of computed tomography: a review of 82
      cases.
AB  - OBJECTIVE: Intracranial suppurative disorders (abscesses and empyemas) continue
      to be common neurosurgical emergencies in South Africa. Cranial extradural
      empyema (EDE) occurs less frequently than its subdural counterpart but remains a
      potentially devastating disease process. We present our 15-year experience with
      this condition in the era of computed tomography. METHODS: Of the 4623 patients
      with intracranial sepsis who were admitted to the neurosurgical unit at Wentworth
      Hospital (Durban, South Africa) during a 15-year period (1983-1997), 76 patients
      with EDEs were identified. An additional six patients who were identified from
      our outpatient records were treated nonsurgically. Analyses were performed with
      respect to clinical, radiological, bacteriological, surgical, and outcome data.
      All information for this study was obtained from the computerized databank for
      the unit. Statistical analyses of the related pre- and postoperative clinical
      data were performed. RESULTS: The 76 patients with EDEs accounted for 1.6% of the
      total number of patients admitted for treatment of intracranial sepsis during the
      study period. Thirteen patients (15.8%) had infratentorial pus collections. Male
      patients predominated by a ratio of 2:1, and 66 patients were between the ages of
      6 and 20 years (mean age, 16.56+/-9.87 yr). The origins of the sepsis were
      paranasal sinusitis for 53 patients (64.6%), mastoiditis for 16 patients, trauma
      for 5 patients, dental caries for 1 patient, and miscellaneous causes for 7
      patients. The most common clinical presenting features were fever, neck
      stiffness, and periorbital edema. Surgery was performed in the form of burrholes
      for 21 patients, small craniectomies for 39 patients, and craniotomies for 5
      patients. The additional five patients, while having drainage of their infected
      paranasal sinuses, had simultaneous drainage of their extradural pus collections
      by the ear, nose, and throat surgeon. The majority of patients (81 patients)
      experienced good outcomes (Glasgow Outcome Scale scores of 4 or 5). A single
      patient died after surgery (mortality rate, 1.22%). CONCLUSION: EDEs occur less
      frequently than subdural empyemas and are associated with better prognoses.
      Surgical drainage (burrholes), simultaneous eradication of the source of sepsis,
      and high-dose intravenous antibiotic therapy remain the mainstays of treatment.
      Selective nonsurgical management of small EDEs is possible, provided the source
      of sepsis is surgically eradicated. It is our opinion that EDE is a disease that
      should be managed without morbidity or death.

PMID- 10201300
TI  - Treatment of symptomatic cervical carotid dissections with endovascular stents.
AB  - OBJECTIVE: Symptomatic dissections of the cervical carotid artery (CCA) can be
      spontaneous or secondary to trauma and may be associated with pseudoaneurysms.
      Surgical treatment is often difficult or unavailable. We report the successful
      use of endovascular stents in the treatment of symptomatic dissection of the CCA.
      METHODS: Five consecutive patients with symptomatic CCA dissection were seen at
      our institution. There were four female patients and one male patient, ranging in
      age from 19 to 56 years. One dissection was spontaneous. The others were
      secondary to a gunshot wound (one patient), blunt neck trauma (two patients), and
      endovascular treatment of atherosclerotic carotid bifurcation disease (one
      patient). Balloon-expandable and self-expanding stents were placed via a
      transfemoral approach. RESULTS: Success in restoring the carotid lumen with two
      to five stents in each patient was angiographically demonstrated. There were no
      procedure-related complications. All patients experienced significant clinical
      improvement within the first 24 hours and complete long-term recovery.
      CONCLUSION: Symptomatic dissections of the CCA can be successfully treated by
      using endovascular stents.

PMID- 10201301
TI  - Cervical spondylotic myelopathy: patterns of neurological deficit and recovery
      after anterior cervical decompression.
AB  - OBJECTIVES: We evaluated the specific pattern of pre- and postoperative
      neurological signs and symptoms and functional results in patients with cervical
      spondylotic myelopathy who underwent anterior decompressive operations.
      Additionally, we sought to determine which findings had predictive value for
      surgical outcome. METHODS: We retrospectively reviewed the records of 76 patients
      with cervical spondylotic myelopathy caused by osteophytic ridge or
      intervertebral disc herniation who underwent anterior cervical decompression and
      fusion performed by one surgeon. The patients were evaluated postoperatively by
      office visits and/or telephone interviews. Outcome was assessed by objective
      neurological examination and scoring with multiple functional rating scales.
      RESULTS: The most common preoperative symptoms were deterioration of hand use
      (75%), upper extremity sensory complaints (82.9%), and gait difficulties (80.3%).
      In the upper extremities, preoperative weakness was most common in the hand
      intrinsic muscles (56.6%) and triceps (28.9%), and in the lower extremities,
      preoperative weakness was most common in the iliopsoas (38.8%) and quadriceps
      (26.3%). In the lower extremities, individual muscle groups had strength
      improvement rates from 79.1 to 88.1 %; somewhat higher rates, from 81.3 to 90.9%,
      were observed in the upper extremities. When evaluated by using the Cooper
      myelopathy scale, lower extremity functional improvement occurred in 46.7% of the
      patients and upper extremity functional improvement in 75.4%. Overall functional
      improvement, evaluated by using a modification of the Japanese Orthopedic
      Association Scale, was noted in 79.7% of the patients who had abnormal scores
      preoperatively. CONCLUSION: Strength improved at rates of approximately 80 to 90%
      in individual muscle groups after anterior cervical decompression. However, fewer
      than half of all patients experienced functional improvement in the lower
      extremities, a discrepancy that was probably caused by persistent spasticity
      rather than muscle weakness. Postoperative dysfunction in the upper extremities
      was caused by residual weakness as well as sensory loss. Recurrent symptomatic
      spondylosis at unoperated levels was calculated to occur at an incidence of 2%
      per year.

PMID- 10201302
TI  - Cervical spondylotic myelopathy: functional and radiographic long-term outcome
      after laminectomy and posterior fusion.
AB  - OBJECTIVE: To evaluate the long-term efficacy of cervical laminectomy with
      posterior lateral mass fusion/fixation in the treatment of patients with cervical
      spondylotic myelopathy (CSM). METHOD: Twenty-five patients treated for CSM by
      laminectomy and lateral mass fusion at the Division of Neurosurgery at The Ohio
      State University between 1989 and 1994 were studied retrospectively. Only
      patients with longer than 2-year postoperative follow-up durations were included.
      At follow-up examination, each patient completed an SF36 questionnaire, underwent
      a physical examination, underwent plain radiography showing the spinal curvature
      with plate and screw position, and underwent magnetic resonance imaging of the
      cervical spine, which evaluated dural sac decompression and spinal cord
      abnormalities. Patient-generated data were used for outcome measurements.
      RESULTS: The mean follow-up duration was 47.5 months. Good outcome was defined by
      the presence of three criteria: ability to walk unassisted (Grade IIIA or
      better), ability to write unassisted, and ability to manage buttons and/or
      zippers unassisted. The inability to meet these criteria was defined as a poor
      outcome. Two patients (8%) experienced complications that resulted from the
      surgery. There was no instability or progression to significant kyphosis. Lesions
      that were hyperintense on magnetic resonance images did not correlate with
      outcome. Eighty percent of the patients achieved good outcomes, and 76% had
      improved myelopathy scores. None of the patients had late neurological
      deterioration. Patients with better neurological statuses at the time of surgery
      (Grade IIIA or better) were more likely to improve (P < 0.0001); the likelihood
      of a change in status for those starting with poorer grades (IIIB or worse) was
      not statistically significant (P < 0.08). CONCLUSION: Cervical laminectomy with
      posterior fusion/fixation proved useful in the treatment of patients with CSM
      with straight or lordotic spines and multilevel compression. This therapy
      addresses the dynamic and compressive forces that are important in the
      pathogenesis of CSM, resulting in minimal complications and possible improvement
      in long-term outcomes.

PMID- 10201303
TI  - Quantitative analysis of cerebrospinal fluid flow in patients with cervical
      spondylosis using cine phase-contrast magnetic resonance imaging.
AB  - OBJECTIVE: To investigate changes in the cerebrospinal fluid flow in patients
      with cervical spondylosis using cine phase-contrast magnetic resonance (MR)
      imaging. METHODS: The participants included 44 healthy volunteers, 11
      asymptomatic patients with evidence of degenerative changes of the cervical spine
      revealed by MR imaging but no neurological symptoms referable to those
      abnormalities, and 23 symptomatic patients with myelopathy who underwent surgery.
      Cervical spondylotic myelopathy was evaluated using the Japanese Orthopedic
      Association scores, and the percentage reduction of the transverse cord area at
      the level of maximum cord compression was measured on T1-weighted magnetic
      resonance images. A cine phase-contrast MR pulse sequence with peripheral gating
      was used to measure the cerebrospinal fluid flow direction and velocity in the
      ventral subarachnoid spaces at the C1 and T1 levels. RESULTS: The velocity
      waveforms produced by plotting flow velocity at 16 intervals during one cardiac
      cycle significantly differed among the healthy volunteers, asymptomatic patients,
      and preoperative symptomatic patients. However, velocity waveforms did not differ
      between the healthy volunteers and the postoperative patients at the C1 level.
      Decreases of flow velocity were significantly correlated with the severity of
      myelopathy and the percentage reduction of cord area. Patients with severe
      myelopathy (Japanese Orthopedic Association score of 0-9 points) or greater than
      30% reduction of cord area showed significantly decreased flow velocity compared
      with those with mild myelopathy (Japanese Orthopedic Association score of 10-17
      points) or less than 30% reduction of cord area. Changes in flow velocity were
      not correlated with multiplicity of the lesion or the level of maximum cord
      compression. Postoperative improvement of flow velocity was not correlated with
      neurological recovery. CONCLUSION: Cine phase-contrast MR imaging allows
      quantitative and noninvasive assessment of changes in cerebrospinal fluid flow in
      patients with cervical spondylosis.

PMID- 10201304
TI  - Emergency magnetic resonance imaging of cervical spinal cord injuries: clinical
      correlation and prognosis.
AB  - OBJECTIVE: The goal of this study was to determine the prognostic and clinical
      value of magnetic resonance imaging (MRI) performed within hours after cervical
      spinal cord injuries in human patients. METHODS: Fifty-five patients with acute
      cervical vertebral column and spinal cord injuries underwent MRI as part of their
      initial treatment at the University of Michigan Medical Center. All images were
      obtained within 21 hours after injury (mean, 7.8 h) and were interpreted by an
      attending neuroradiologist who was blinded to the clinical status of the
      patients. Neurological function at presentation and in long-term follow-up
      examinations was compared with MRI characteristics assessed immediately after the
      injury. RESULTS: The presence and rostrocaudal length of intra-axial hematoma,
      the rostrocaudal length of spinal cord edema, the presence of spinal cord
      compression, and spinal cord compression by extra-axial hematoma were each
      significantly associated with poor neurological function at presentation and in
      long-term follow-up examinations. Although the best single predictor of long-term
      improvement in neurological function was the neurological function at
      presentation, four MRI characteristics, i.e., the presence of intra-axial
      hematoma, the extent of spinal cord hematoma, the extent of spinal cord edema,
      and spinal cord compression by extra-axial hematoma, provided significant
      additional prognostic information. MRI data demonstrated spinal cord compression
      for 27 of 55 patients (49%), leading to emergency surgery. Among patients who
      underwent imaging after restoration of normal vertebral alignment using closed
      cervical traction, 13 of 26 (50%) underwent emergency surgery for treatment of
      persistent, MRI-demonstrated, spinal cord compression. CONCLUSION: Emergency MRI
      after spinal cord injury provides accurate prognostic information regarding
      neurological function and aids in the diagnosis and treatment of persistent
      spinal cord compression after vertebral realignment.

PMID- 10201305
TI  - Endoscopic third ventriculostomy: outcome analysis of 100 consecutive procedures.
AB  - OBJECTIVE: Endoscopic third ventriculostomy (ETV) has been shown to be a
      sufficient alternative in the surgical treatment of occlusive hydrocephalus. To
      elucidate the ongoing discussion of timing, indication, and surgical technique, a
      retrospective analysis of 100 consecutive ETVs was conducted. METHODS: One
      hundred ETVs were performed in 95 patients (43 female and 52 male patients).
      Their age ranged from 3 weeks to 77 years (mean age, 36 yr). Hydrocephalus was
      caused by aqueductal stenosis in 40 patients, space-occupying lesions in 42, and
      intraventricular or subarachnoid hemorrhage in 8. One patient had
      postinflammatory hydrocephalus, and four patients had occlusive hydrocephalus of
      unknown origin. In 33 cases, surgery was performed using stereotactic guidance.
      RESULTS: ETV was accomplished in 98 of 100 cases. The overall success rate was
      76%. Patients with benign space-occupying lesions and nontumorous aqueductal
      stenosis had the highest success rates, which were 95 and 83%, respectively.
      Complications were arterial bleeding in one case, venous bleeding in three cases,
      intracerebral bleeding in one case, and infection in one case. There were no
      permanent morbidities or mortalities. CONCLUSION: ETV is most effective in
      treating uncomplicated occlusive hydrocephalus caused by aqueductal stenosis and
      space-occupying lesions. ETV is still effective in two-thirds of the patients
      with previous infections or intraventricular bleeding. Patients who have
      previously undergone shunting and who have occlusive hydrocephalus should undergo
      ETV at the time of shunt failure, with immediate ligation or removal of the shunt
      device. In selected cases of distorted anatomy or impaired visual conditions,
      stereotactic guidance is helpful.

PMID- 10201306
TI  - Brain biopsy using high-field strength interventional magnetic resonance imaging.
AB  - OBJECTIVE: Lesions within the brain are commonly sampled using stereotactic
      techniques. The advent of interventional magnetic resonance imaging (MRI) now
      allows neurosurgeons to interactively investigate specific regions, with
      exquisite observational detail. We evaluated the safety and efficacy of this new
      surgical approach. METHODS: Between January 1997 and June 1998, 35 brain biopsies
      were performed in a high-field strength interventional MRI unit. All biopsies
      were performed using MRI-compatible instrumentation. Interactive scanning was
      used to confirm accurate positioning of the biopsy needle within the region of
      interest. Intraoperative pathological examination of the biopsy specimens was
      performed to verify the presence of diagnostic tissue, and intra- and
      postoperative imaging was performed to exclude the presence of intraoperative
      hemorrhage. Recently, magnetic resonance spectroscopic targeting was used for six
      patients. RESULTS: Diagnostic tissue was obtained in all 35 brain biopsies and
      was used in therapeutic decision-making. Histological diagnoses included 28
      primary brain tumors (12 glioblastomas multiforme, 9 oligodendrogliomas, 2
      anaplastic astrocytomas, 2 astrocytomas, 1 lymphoma, and 1 anaplastic
      oligodendroglioma), 1 melanoma brain metastasis, 1 cavernous sinus meningioma, 1
      cerebral infarction, 1 demyelinating process, and 3 cases of radiation necrosis.
      In all cases, magnetic resonance spectroscopy was accurate in distinguishing
      recurrent tumors (five cases) from radiation necrosis (one case). No patient
      sustained clinically or radiologically significant hemorrhage, as determined by
      intraoperative imaging performed immediately after the biopsy. One patient (3%)
      suffered transient hemiparesis after a pontine biopsy for investigation of a
      brain stem glioma. Another patient developed scalp cellulitis, with possible
      intracranial extension, 3 weeks after the biopsy; this condition was effectively
      treated with antibiotic therapy. Three patients were discharged on the day of the
      biopsy. CONCLUSION: Interventional 1.5-T MRI is a safe and effective method for
      evaluating lesions of the brain. Magnetic resonance spectroscopic targeting is
      likely to augment the diagnostic yield of brain biopsies.

PMID- 10201307
TI  - Visual evoked potentials during posteroventral pallidotomy for Parkinson's
      disease.
AB  - OBJECTIVE: To examine the efficacy of intracerebral recording of visual evoked
      potentials (VEPs) during posteroventral pallidotomy comparing macro- and
      microelectrode stimulation. MATERIALS AND METHODS: The optic tract was identified
      by intracerebral recording of VEPs in 16 patients. Electrical stimulation through
      a lesioning electrode (macroelectrode stimulation: biphasic wave, 50 Hz, 0.2 ms,
      0-6 V) and a microelectrode (microelectrode stimulation: impedance of 1 M(omega)
      at 300 Hz, biphasic pulse, 300 Hz, 0.2 ms, 10-50 microA) was delivered to assess
      visual responses. RESULTS: VEPs were recorded in every patient from 18.0+/-3.3 mm
      (n = 14) to 22.8+/-3.4 mm (n = 14) in the mediolateral direction. The mean
      amplitude at this midpoint (57.7+/-15.4 microV, n = 35) was significantly higher
      than other amplitudes (t test, P < 0.05). Significant increment of amplitudes
      appeared at 4 mm (64.3+/-18.5 microV, n = 16) below the initial target along
      trajectories that pass close to the midpoint of the optic tract. The distance
      from the initial target to the dorsal surface of the optic tract along these
      trajectories ranged from 3 to 6 mm, with a mean of 5.0+/-0.7 mm (n = 16), whereas
      adjusted distances perpendicular to the intercommissural plane ranged from 1.3 to
      4.1 mm, with a mean of 3.0+/-0.7 mm (n = 16) below, and the distance from the
      optic tract to the intercommissural plane ranged from 6.3 to 8.7 mm, with a mean
      of 7.5+/-0.7 mm (n = 16). Macroelectrode stimulation evoked visual responses at
      various sites in the pallidal region, totaling 27 sites in 11 of 16 patients
      (68.7%). Microelectrode stimulation evoked responses at only five sites in 3 of
      13 patients (23.1 %), within a very limited area 4 to 7 mm below the target where
      the electrode was very close to the optic tract. Physiological targeting of VEPs
      necessitated change of the initial target in 13 of 16 patients (81.2%).
      CONCLUSION: VEPs of prominent oscillatory potentials with high amplitudes
      indicate the location of the optic tract, which allows easy identification of the
      optic tract and facilitates neurophysiological targeting of the globus pallidus
      internus in conjunction with microelectrode recording.

PMID- 10201308
TI  - Evaluation and surgical management of peripheral nerve problems.
AB  - OBJECTIVE: To illustrate how an understanding of the basic biological responses
      of peripheral nerves to injury is important in formulating a rational treatment
      plan. METHODS: Peripheral nerve anatomy and physiology are described in a context
      that is relevant to understanding the different grades of peripheral nerve
      injury. Methods of evaluating and treating peripheral nerve injuries both
      medically and surgically are reviewed. Relevant scientific studies with potential
      clinical impact are also discussed. RESULTS: The clinical symptoms, physical
      findings, and electrodiagnostic and imaging test results relevant to the
      diagnosis of peripheral nerve problems are reviewed. Conventional and new medical
      or surgical strategies in the management of peripheral nerve injuries and mass
      lesions are described. CONCLUSION: The diagnosis and treatment of peripheral
      nerve injuries follow logically from an understanding of the biological responses
      of peripheral nerves after injury and during recovery.

PMID- 10201310
TI  - Neonatal galenic arteriovenous malformation.

PMID- 10201309
TI  - Morphometric aspects of extraforaminal lumbar nerve roots.
AB  - OBJECTIVE: In the posterolateral extraforaminal and anterolateral retroperitoneal
      approaches to lumbar spinal lesions, the neural structures in the lumbar
      extraforaminal region are unfamiliar to many spinal surgeons. The purpose of this
      study was to determine the normal anatomic morphometric parameters for all lumbar
      nerve roots around their exits, from the intervertebral foramen to the
      surrounding bony structure. METHODS: A total of 15 adult fixed cadavers were
      studied. The extraforaminal course of the lumbar nerve roots and the forming
      plexus were measured segmentally, using standard calipers, and we selected the
      shortest distance from the bony landmarks to the nerve roots in the horizontal
      plane. The bony landmarks were the most medial superior border of the transverse
      process (TP), the most medial inferior border of the TP, the tip of the superior
      articular process, and the most dorsolateral margin of the intervertebral disc
      space. In addition, the angle of each root exiting from the intervertebral
      foramen was measured using a goniometer. RESULTS: The mean distance from the
      medial superior border of the TP to the upper segment of the nerve root was 5.1
      to 6.4 mm at L2-L5. The mean distance from the medial inferior border of the TP
      to the corresponding nerve root was 8.5 mm at L2 and L3 and 6 mm at L4 and L5.
      The mean distance from the tip of the superior articular process to the most
      dorsal border of the descending nerve trunk was 19 mm at L2 and L3 and 22 mm at
      L4 and L5. The main lumbar nerve trunk was located close to the most dorsolateral
      surface of the vertebral body and the intervertebral disc space, and it was
      topographically arranged dorsoventrally from the L5 to L2 nerve components. The
      average widths of the nerve trunk were 10, 14, and 25 mm at L3-L4, L4-L5, and L5
      S1, respectively. The mean angles of the exiting roots in the extraforaminal
      region were 16 degrees at L2 and L3 and 25 degrees at L4 and L5. CONCLUSION: The
      lumbar nerve component, including both the lumbar trunk and each exiting nerve
      root in the extraforaminal region (the so-called "danger zone"), was located
      anteriorly at a distance more than 5 mm from the TP, more than 19 mm from the
      superior articular process, and up to 25 mm from the intervertebral disc space.
      Based on our results, the danger zone occupied up to 25 mm forward from the
      intervertebral foramen at the lower lumbar segments. Therefore, during operations
      such as percutaneous posterolateral procedures and open posterolateral or
      anterolateral approaches, great care should be taken within 25 mm of the
      extraforaminal region, especially for the lower lumbar spine.

PMID- 10201311
TI  - Foreign body granuloma mimicking intracranial meningioma: case report and review
      of the literature.
AB  - OBJECTIVE AND IMPORTANCE: Intracranial foreign body granulomas are rare. We
      describe a case of an intracranial foreign body granuloma found in a 17-year-old
      female patient 9 years after she underwent a craniotomy for a tumor of unknown
      type. Postoperative imaging of patients who have undergone neurosurgical
      procedures can often reveal enhancing masses, and foreign body granuloma should
      be included in the differential diagnosis. CLINICAL PRESENTATION: The patient
      presented with a history of developmental delay, panhypopituitarism, and chronic
      headache. Admission resulted from an acute increase in the severity of her
      headache. INTERVENTION: Imaging studies, including computed tomography and
      magnetic resonance imaging, demonstrated a 1.5 x 2 cm round, enhancing anterior
      interhemispheric mass, appearing to arise from the falx and causing mild mass
      effect. A nonenhancing cystic mass was also noted in the suprasellar region but
      was without mass effect. The patient underwent a craniotomy and removal of the
      anterior mass without complication, and her headache resolved. A pathological
      examination of the specimen confirmed the diagnosis of foreign body granuloma.
      CONCLUSION: Although rare, foreign body granuloma should be included in the
      differential diagnosis of previously operated intracranial masses. The importance
      of accurate historical information and guidelines that may assist in diagnosis
      are discussed.

PMID- 10201312
TI  - Primary lymphoma of Meckel's cave mimicking trigeminal schwannoma: case report.
AB  - OBJECTIVE AND IMPORTANCE: We report the first case of primary lymphoma of
      Meckel's cave. The ability of a lymphoma to mimic a trigeminal schwannoma, both
      clinically and radiographically, resulted in misdiagnosis and flawed surgical
      strategy. We discuss the characteristics of a Meckel's cave lymphoma on magnetic
      resonance images, the predisposing medical conditions that should cause the
      neurosurgeon to add lymphoma to the normal differential diagnosis, and
      appropriate management strategies. CLINICAL PRESENTATION: A 40-year-old African
      American woman presented with a 5-month history of progressive facial numbness
      and pain in all three divisions of the left trigeminal nerve. Magnetic resonance
      imaging revealed a mass in the left side of Meckel's cave, with extension into
      the lateral compartment of the cavernous sinus, without encasement of the
      internal carotid artery, through the foramen rotundum into the posterior aspect
      of the maxillary sinus, and through the foramen ovale into the pterygopalatine
      fossa. The diagnosis, based on clinical history and radiographic imaging, was
      schwannoma of Meckel's cave. The patient had a history of systemic lupus
      erythematosus that had been treated with intermittent steroid therapy.
      INTERVENTION: The surgical approach selected was a frontotemporal craniotomy with
      orbitozygomatic osteotomy and anterior petrosectomy. The lesion was totally
      excised, although the gross intraoperative appearance of the lesion was
      inconsistent with the preoperative diagnosis, and the pathological examination
      was unable to establish a histological diagnosis on the basis of frozen sections.
      Histological diagnosis was confirmed on permanent section after surgery as B-cell
      lymphoma. Evaluation for other primary sites produced negative results. The
      patient was then treated with cyclophosphamide (Cytotoxan; Bristol-Myers
      Oncology, Princeton, NJ), doxorubicin (Adriamycin; Pharmacia & Upjohn, Kalamazoo,
      MI), vincristine, and prednisone chemotherapy every 3 weeks for six cycles and
      then by radiation therapy to the affected area. CONCLUSION: The diagnosis of
      lymphoma should be considered for lesions affecting Meckel's cave in high-risk
      immunocompromised patients. The presence of an apparent dural tail in an
      otherwise typical schwannoma is the distinguishing characteristic of a lymphoma.
      The absence of hyperostosis helps differentiate it from a meningioma. At this
      point, the preferred surgical strategy is biopsy for diagnosis and then
      radiotherapy and chemotherapy rather than major cranial base surgery for total
      resection.

PMID- 10201313
TI  - Infratentorial subdural empyema, pituitary abscess, and septic cavernous sinus
      thrombophlebitis secondary to paranasal sinusitis: case report.
AB  - OBJECTIVE AND IMPORTANCE: Infratentorial empyema, pituitary abscess, and septic
      cavernous sinus thrombophlebitis are all rare and potentially lethal conditions.
      The occurrence of all three in a single patient has not previously been
      described. We present such a case occurring in a young, otherwise healthy man.
      CLINICAL PRESENTATION: A 26-year-old man with a remote history of sinusitis
      developed rapidly progressive headache, fever, right eye pain, swelling,
      proptosis, and visual impairment. Magnetic resonance imaging demonstrated diffuse
      pansinusitis, including sphenoid sinusitis, and extension of inflammation and
      infection into the adjacent cavernous sinuses, pituitary gland, and posterior
      fossa. INTERVENTION: Urgent drainage of the ethmoid and maxillary sinuses was
      performed; pus was not identified. The patient continued to deteriorate
      clinically with worsening of visual acuity. Computed tomography of the head
      performed the next day revealed worsening hydrocephalus and an enlarging
      posterior fossa subdural empyema. Urgent ventricular drainage and evacuation of
      the empyema was performed, and subsequently, the patient's clinical course
      improved. The microbiology results revealed alpha hemolytic streptococcus and
      coagulase-negative staphylococcus species. The patient survived but during the
      follow-up period had a blind right eye and pituitary insufficiency. CONCLUSION:
      Paranasal sinusitis can have devastating intracranial sequelae. Involvement of
      the adjacent pituitary gland and cavernous sinuses can result in serious
      neurological morbidity or mortality, and retrograde spread of infection through
      the basal venous system can result in subdural or parenchymal brain involvement.
      A high index of suspicion and aggressive medical and surgical treatment are
      crucial for patient survival, but the morbidity rate remains high. Our patient
      survived but lost anterior pituitary function and vision in his right eye.

PMID- 10201314
TI  - Intradiploic arachnoid cyst with extensive deformation of craniofacial osseous
      structures: case report.
AB  - OBJECTIVE AND IMPORTANCE: A unique case of a large intradiploic arachnoid cyst
      involving craniofacial osseous structures is reported. CLINICAL PRESENTATION: The
      patient presented with a hard mass in the right frontal region, proptosis, and
      inferior globe displacement. Computed tomography revealed an intraosseous cyst of
      cerebrospinal fluid intensity with extension from the anterior cranial fossa to
      the infratemporal fossa. INTERVENTION: After resection of the cyst wall and
      closure of two small round dural defects, the involved craniofacial region was
      reconstructed. CONCLUSION: The medical history of the patient and the
      intraoperative observations support the contention that the cyst in the reported
      case was congenital in origin. The features concerned with diagnosis and
      pathogenesis of this rare entity are discussed.

PMID- 10201315
TI  - De novo formation of familial cerebral aneurysms: case report.
AB  - OBJECTIVES: The factors regulating the formation and growth of cerebral aneurysms
      are poorly understood. We report the case of a patient whose grandfather had a
      cerebral aneurysm and who developed numerous de novo aneurysms of varying size 9
      years after the treatment of a first aneurysm. This observation sheds light on
      the cause and growth of cerebral aneurysms in familial cases that may be
      pertinent to sporadic cases. CLINICAL PRESENTATION: A 58-year-old man was
      admitted to the Montreal Neurological Institute in 1956 for an ultimately fatal,
      autopsy-proven, ruptured internal carotid artery aneurysm. His granddaughter was
      first admitted to the same institution in 1984 after suffering a subarachnoid
      hemorrhage from a ruptured right terminal internal carotid artery aneurysm that
      was successfully treated. Four-vessel cerebral angiography did not reveal other
      aneurysms. The granddaughter was readmitted to the hospital 9 years later after a
      new, lumbar puncture-proven subarachnoid hemorrhage occurred. Cerebral
      angiography demonstrated that the previously clipped aneurysm did not fill.
      However, five new aneurysms were present. INTERVENTION: An anterior communicating
      artery aneurysm, thought to be the one that bled, was surgically clipped, and a
      large right posterior communicating artery aneurysm was coiled endovascularly.
      The remaining, smaller aneurysms were left untreated. CONCLUSION: The appearance
      of five new aneurysms during a 9-year interval suggests that there may be a
      genetic factor operating in the development of cerebral aneurysms in families and
      that this may produce a more widespread cerebral arteriopathy than is generally
      appreciated. Patients with treated cerebral aneurysms from families in which two
      or more individuals have cerebral aneurysms, and perhaps their first and second
      degree relatives who have had negative angiograms, should be considered for
      periodic follow-up cerebrovascular imaging to rule out the subsequent development
      of de novo aneurysms.

PMID- 10201316
TI  - Spinal dural arteriovenous fistula with an associated feeding artery aneurysm:
      case report.
AB  - OBJECTIVE AND IMPORTANCE: A case of a spinal dural arteriovenous fistula (DAVF)
      with two associated feeding artery aneurysms is reported. Intradural spinal
      arteriovenous malformations have been associated with aneurysms that present with
      subarachnoid hemorrhage and with venous varices that produce mass effect, but
      spinal DAVFs have not previously been described in association with feeding
      artery aneurysms. CLINICAL PRESENTATION: A 71-year-old man presented with
      progressive spastic paraparesis, constipation, and overflow incontinence.
      Magnetic resonance imaging demonstrated a spinal vascular lesion and venous
      ischemia in the lower spinal cord. Diagnostic spinal angiography revealed a DAVF
      originating from the left T11 radicular artery and having the unusual feature of
      two proximal feeding artery aneurysms. INTERVENTION: The patient deteriorated
      neurologically after undergoing angiography, prompting emergent surgery. The DAVF
      was resected through a T11 transpedicular approach. One aneurysm was
      dolichoectatic and therefore unclippable, requiring proximal occlusion of the
      parent artery after establishing tolerance of test occlusion using somatosensory
      evoked potentials; the second aneurysm was adjacent to the fistula and was
      resected with the DAVF. CONCLUSION: Feeding artery aneurysms in association with
      spinal DAVFs have not been previously reported. They present additional risk to
      patients and, with simple modifications of the standard operative approaches, can
      easily be treated as part of the surgery for the DAVF.

PMID- 10201317
TI  - Adenosine-induced cardiac pause for endovascular embolization of cerebral
      arteriovenous malformations: technical case report.
AB  - OBJECTIVE: Extremely high flow through arteriovenous malformations (AVMs) may
      limit the safety and effectiveness of endovascular glue therapy. To achieve a
      more controlled deposition of glue, we used transient but profound systemic
      hypotension afforded by an intravenously administered bolus of adenosine to
      induce rapidly reversible high-degree atrioventricular block. METHODS AND CASE
      REPORT: A patient with a large high-flow occipital AVM fed primarily by the
      posterior cerebral artery underwent n-butyl cyanoacrylate glue embolization.
      Nitroprusside-induced systemic hypotension did not adequately reduce flow through
      the nidus, as determined by contrast injection in the feeding artery. In a dose
      escalation fashion, boluses of adenosine were administered to optimize the dose
      and verify that there was no flow reversal in the AVM and no other unexpected
      hemodynamic abnormalities by arterial pressure measurements and transcranial
      Doppler monitoring of the posterior cerebral artery feeding the AVM. Thereafter,
      64 mg of adenosine was rapidly injected as a bolus to provide 10 to 15 seconds of
      systemic hypotension (approximately 20 mm Hg). Although there were conducted
      beats and some residual forward flow through the AVM during this time, the mean
      systemic and feeding artery pressures were roughly similar and remained
      relatively constant. A slow controlled injection of n-butyl cyanoacrylate glue
      was then performed, with excellent filling of the nidus. CONCLUSION: Adenosine
      induced cardiac pause may be a viable method of partial flow arrest in the
      treatment of cerebral AVMs. Safe, deep, and complete embolization with a
      permanent agent may increase the likelihood of endovascular therapy's being
      curative or may further improve the safety of microsurgical resection.

PMID- 10201318
TI  - Resection of a large arteriovenous fistula of the brain using low-flow deep
      hypothermic cardiopulmonary bypass: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: We present the second report in the literature on the
      use of low-flow hypothermic cardiopulmonary bypass to aide in the surgical
      resection of a large intraparenchymal arteriovenous fistula. CLINICAL
      PRESENTATION: The patient was a 46-year-old man who was found to have a left
      sylvian arteriovenous fistula with a giant varix during a workup for chronic left
      frontal headaches and was referred to our center for management. A cardiac workup
      revealed a cardiac output of 9 L per minute. INTERVENTION: Endovascular
      embolization of the lesion was initially attempted without success because of the
      high flow within the lesion and the large diameter of the feeding arteries. We
      then planned combined and staged endovascular and surgical approaches to
      gradually eliminate the fistula. Endovascular embolization, both transarterial
      and transvenous, could not be performed because of the high flow in the fistula.
      Despite the stepwise reduction of flow during the course of several weeks via
      surgical exposures and arterial ligations, the fistula remained difficult to
      remove because of its size and the turgor of the varix. Once hypothermic low-flow
      circulatory bypass was used, however, decompression of the sac allowed access to
      the afferent vasculature. CONCLUSION: The use of low-flow hypothermic circulatory
      bypass can facilitate the surgical extirpation of certain large intraparenchymal
      arteriovenous fistulas.

PMID- 10201319
TI  - Surgical management of angiographically occult spinal dural arteriovenous
      fistulae (type I spinal arteriovenous malformations): three technical case
      reports.
AB  - OBJECTIVE AND IMPORTANCE: Spinal dural arteriovenous fistulae (Type I spinal
      arteriovenous malformations [AVMs]) have been recognized as a treatable cause of
      progressive myelopathy. The diagnosis and characterization of these lesions rest
      heavily on spinal angiography. CLINICAL PRESENTATION: We present three patients
      whose clinical presentations were consistent with a spinal dural AVM but whose
      spinal angiographic results were negative. INTERVENTION: The surgical treatment
      of these angiographically occult spinal AVMs is described. In retrospect, in each
      case, the feeding vessel to the AVM was injected but not seen. CONCLUSION: Some
      spinal dural arteriovenous fistulae will be angiographically occult. If the
      clinical and radiographic presentations strongly suggest the presence of an
      arteriovenous fistula, surgical exploration should be considered.

PMID- 10201321
TI  - Reliability of cranial flap fixation techniques: comparative experimental
      evaluation of suturing, titanium miniplates, and a new rivet-like titanium clamp
      (CranioFix): technical note.
AB  - OBJECTIVE: To ensure patients' safety, the mechanical strength of cranial flap
      refixation techniques and implants (sutures, titanium miniplates, and new rivet
      like titanium clamps) had to be validated. METHODS: With craniotomied cadaver
      skulls for each refixation technique, load-bearing tests were performed by
      applying an external force until an impression depth of the cranial flap of 2 mm
      was reached and the results were compared. RESULTS: CranioFix (Aesculap AG,
      Tuttlingen, Germany) and miniplates were revealed to be the strongest fixation
      devices, although with miniplates, the plastic deformation started from the
      beginning of load application, whereas CranioFix additionally provided a better
      spring-elastic reserve and a higher reproducibility of fixation strength not
      dependent on bone thickness and consistency. Flaps fixed by sutures were
      dislocated from the start. CONCLUSION: Although CranioFix offers distinct
      advantages over miniplates, both proved to be definitely superior to suturing,
      which is still used in many centers. Therefore, whether suturing can still be
      regarded as a state-of-the-art technique must be reconsidered.

PMID- 10201320
TI  - Endovascular recanalization with balloon angioplasty and stenting of an occluded
      occipital sinus for treatment of intracranial venous hypertension: technical case
      report.
AB  - OBJECTIVE AND IMPORTANCE: Dural sinus thrombosis can lead to intracranial venous
      hypertension and can be complicated by intracranial hemorrhage. We present a case
      report of a patient who underwent endovascular recanalization and stenting of a
      thrombosed occipital sinus. CLINICAL PRESENTATION: A 13-year-old patient with a
      history of chronic sinus thrombosis refractory to anticoagulant therapy presented
      with acute onset of aphasia and hemiparesis. Computed tomography and magnetic
      resonance imaging revealed hydrocephalus and cerebral edema. Angiography
      delineated multiple dural arteriovenous fistulae and persistent occlusion of the
      posterior sagittal, occipital, and bilateral transverse dural sinuses with
      retrograde cortical venous drainage. INTERVENTION: After embolization of the
      dural arteriovenous fistulae, a transvenous approach was used to recanalize and
      perform balloon angioplasty of the right internal jugular vein and the occipital
      and left transverse sinuses, resulting in subsequent clinical improvement. The
      patient's condition deteriorated 3 days later with reocclusion of both balloon
      dilated sinuses. Repeat angioplasty and then deployment of an endovascular stent
      in the occipital sinus were performed, and reestablishment of venous outflow was
      achieved, resulting in a decrease of intracranial venous pressure from 41 to 14
      mm Hg and neurological improvement. At the 3-month follow-up examination, the
      stented occipital sinus remained patent and served as the only conduit for
      extracranial venous outflow; the patient remained neurologically intact at the 12
      month follow-up examination. CONCLUSION: This is the first report of mechanical
      recanalization, balloon angioplasty, and stent deployment in the occipital sinus
      to provide sustained venous outflow for the treatment of venous hypertension with
      retrograde cortical venous drainage in a patient with dural pansinus thrombosis
      refractory to anticoagulant therapy.

PMID- 10201322
TI  - Library: historical perspective.

PMID- 10201323
TI  - A prospective randomized study of anterior single-level cervical disc operations
      with long-term follow-up: surgical fusion is unnecessary.

PMID- 10201324
TI  - Outcomes research: a review.

PMID- 10201325
TI  - Reliability of epidural pressure measurement in clinical practice: behavior of
      three modern sensors during simultaneous ipsilateral intraventricular or
      intraparenchymal pressure measurement.

PMID- 10201326
TI  - The history of neurological surgery at Northwestern University.

PMID- 10201327
TI  - Trace elements in coal: environmental and health significance.
AB  - Trace elements can have profound adverse effects on the health of people burning
      coal in homes or living near coal deposits, coal mines, and coal-burning power
      plants. Trace elements such as arsenic emitted from coal-burning power plants in
      Europe and Asia have been shown to cause severe health problems. Perhaps the most
      widespread health problems are caused by domestic coal combustion in developing
      countries where millions of people suffer from fluorosis and thousands from
      arsenism. Better knowledge of coal quality characteristics may help to reduce
      some of these health problems. For example, information on concentrations and
      distributions of potentially toxic elements in coal may help delineate areas of a
      coal deposit to be avoided. Information on the modes of occurrence of these
      elements and the textural relations of the minerals in coal may help to predict
      the behavior of the potentially toxic trace metals during coal cleaning,
      combustion, weathering, and leaching.

PMID- 10201328
TI  - State of pregnancy modifies lead toxicity in mice.
AB  - Toxicity of lead acetate after administration through the oral route at 0-50
      mg/kg body weight of animal has been assessed in the liver of pregnant mice and
      compared with the effect in the liver of nonpregnant dams. Analysis showed that
      the basal level of hepatic lead is considerably reduced during pregnancy as
      compared to that in nonpregnant state. After administration of Pb-acetate,
      deposited lead in liver of nonpregnant mice was 3- to 4-fold while in pregnant
      mice was, it was 1.8- to 3.0-fold over their respective control values. Although
      hepatic Fe, Cu, and Zn levels had a tendency to be lowered during pregnancy, it
      appeared that the added trace quantity of lead prior to and during pregnancy
      helped in the retention of these metals, which either remained unaffected (as Fe)
      or declined (Cu and Zn) after lead administration during the nonpregnant state.
      The effect of lead on Mn diminution, however, was visible at the dose of 50 mg/kg
      body wt of lead-acetate. Alkaline phosphatase, which increased during pregnancy
      along with Mn, was reversed between the pregnant and nonpregnant states after
      oral administration of lead. On the other hand, the level of delta-aminolevolunic
      acid dehydratase, which declined during normal pregnancy, continued to fall
      further after lead exposure. It is concluded that the distribution of basal or
      administered lead and its effect on enzyme activities and trace metal composition
      in liver depends on the pregnant and nonpregnant states of female hosts.

PMID- 10201329
TI  - Atrial natriuretic peptide relation to plasma and heart zinc concentrations of
      Wistar rats exposed to cold and hot ambients.
AB  - Plasma atrial natriuretic peptide (ANP) and zinc levels, as well as heart tissue
      zinc concentrations were determined, in male Wistar rats after the exposure of
      114 rats at low temperature (4 degrees C) and 95 rats at high temperature (35-36
      degrees C) for 28 d. Plasma ANP was estimated by radioimmunoassay and Zn2+
      concentrations by atomic absorption spectrometry. Values were compared to a
      control group exposed at 20-22 degrees C (76 rats). Plasma ANP and Zn2+ levels,
      as well as heart tissue Zn2+ concentrations of control rats did not show
      statistically significant variations during the study, whereas rats exposed to
      cold and hot ambients showed significant variations of the parameters. A
      significant increase of plasma ANP and plasma zinc and heart tissue Zn2+
      concentrations developed during cold exposure, whereas a gradual decrease of
      plasma ANP and Zn2+ levels was revealed during hot adaptation. Results also
      indicate that plasma ANP and zinc levels are proportionally related, whereas
      there is an inverse relationship between plasma ANP levels and heart Zn2+
      concentrations, in both cold and hot exposed rats. In conclusion, our results
      show that ANP in relation to zinc probably play an important role in cold and hot
      acclimatization of rats.

PMID- 10201330
TI  - Elemental composition of human milk from mothers of premature and full-term
      infants during the first 3 months of lactation.
AB  - To examine longitudinal and gestational effects of mineral content in human milk,
      we analyzed human milk from lactating mothers of premature (PRT, n = 24, < 2000 g
      birth weight, < 37 wk gestation) and full-term (FT, n = 19, > 2500 g, 39-41 wk
      gestation), living in Newfoundland, Canada. Samples were collected once a week
      for 8 wk with one final sample collected at 3 mo. Milk samples collected in acid
      washed containers were wet ashed with concentrated HNO3, and barium, cadmium,
      calcium, cesium, cobalt, copper, cerium, lanthanum, magnesium, manganese,
      molybdenum, nickel, lead, rubidium, tin, strontium, and zinc were measured using
      inductively coupled plasma-mass spectrometry. Data were analyzed using standard
      multiple-regression procedures with correlated data analyses to take account of
      the relationship between successive weeks. Results indicated lower Ca and Pb in
      PRT milk. Calcium was the only nutritionally significant element to differ
      between groups. Molybdenum in both PRT and FT milk showed a definite decrease
      with time, suggesting that the Mo content in milk is homeostatically regulated.
      However, Ce, La, Ba, and Sn did not display any pattern indicative of biological
      regulation and potential human requirement.

PMID- 10201331
TI  - In vitro dialyzability using meal approach as an index for zinc and iron
      absorption in humans.
AB  - With a standardized protocol under simulated gastrointestinal conditions, 65Zn
      and 59Fe dialyzability was measured for 38 diets from 7 different published
      studies on human absorption. The compositions of these diets were available in
      the form of the amounts of food ingredients used for breakfast, lunch, and
      dinner. Considering each of these types as a separate meal, percent dialyzability
      was measured. The weighted average of breakfast, lunch, dinner, and snacks, if
      any, was taken to represent the entire day's bioavailability. The correlation
      between in vitro percent dialyzability and reported human absorption was 0.92 for
      zinc and 0.96 for iron and both were statistically significant (p = 0.0001). The
      prediction equations for zinc and iron were obtained as y = -0.7718 + 1.1038x and
      y = 0.3197 + 0.9084x, respectively. This indicated that in vitro dialyzability
      using the meal approach can be used as an index with good discriminating power
      for different levels of human absorption.

PMID- 10201332
TI  - Zinc sulfate supplementation improves thyroid function in hypozincemic Down
      children.
AB  - In subjects affected by trisomy 21 (Down syndrome), hypothyroidism is the most
      common endocrinological deficit. Plasma zinc levels, which are commonly detected
      below the normal range in Down patients, are related to some endocrinological and
      immunological functions; in fact, zinc deficiency has been shown to impair immune
      response and growth rate. Aims of this study were to evaluate (1) the role of
      zinc deficiency in subclinical hypothyroidism and (2) thyroid function changes in
      Down children cyclically supplemented with zinc sulfate. Inverse correlations
      have been observed between age and triiodotironine (T3) and between zinc and
      thyroid-stimulating hormone (TSH); higher TSH levels have been found in
      hypozincemic patients at the beginning of the study. After 6 mo of
      supplementation, an improvement of thyroid function (TSH levels: 3.96 +/- 1.84 vs
      2.64 +/- 1.33 mUI/mL basally and after 6 mo, respectively) was observed in
      hypozincemic patients. In the second cycle of supplementation, a similar trend of
      TSH was observed. At the end of the study, TSH significantly decreased in treated
      hypozincemic subjects (4.48 +/- 1.93 vs 2.96 +/- 1.20 mUI/mL) and it was no
      longer different in comparison to normozincemic patients. We suggest zinc
      supplementation to the diet in hypozincemic Down children as a simple and useful
      therapeutic tool.

PMID- 10201333
TI  - Age-related changes of elements in the human articular disk of the
      temporomandibular joint.
AB  - To elucidate compositional changes of the articular disk (AD) of the
      temporomandibular joint (TMJ) by aging, elements of the ADs resected from 18
      cadavers were determined by inductively coupled plasma atomic-emission
      spectrometry. It was found that calcium contents of ADs in TMJs increased
      progressively with aging, whereas the sulfur contents of the ADs decreased
      slightly with aging. Regarding the content of phosphorus, the contents increased
      progressively with aging. The study revealed that age-related changes of calcium
      contents in the ADs of TMJs were similar to those in women's pubic symphyses, but
      not those in intervertebral disks and menisci.

PMID- 10201334
TI  - The effect of lanthanide chloride on abscisic acid and electron-transport
      activity of some crops.
AB  - The abscisic acid (ABA) content of the root tips of four crops grown in
      lanthanide chloride solution and their root lengths had been determined. At
      lanthanide concentrations of 5 and 10 ppm, these crops all grew well and the ABA
      decreased. At higher lanthanide concentrations (100-500 ppm), the ABA is
      increased again. At these concentrations of lanthanum chloride, the photosystems
      I and II (PSI and PSII) and whole electron chain transport activities were
      inhibited. PSII was more sensitive than PSI, and it is concluded that La3+ acts
      on the diphenylcarbazide (DPC) action place of PSII oxidizing site.

PMID- 10201335
TI  - Recommendations for the treatment of lipid disorders in patients on peritoneal
      dialysis. ISPD guidelines/recommendations. International Society for Peritoneal
      Dialysis.

PMID- 10201336
TI  - Does a high peritoneal transport rate reflect a state of chronic inflammation?
AB  - OBJECTIVE: It has recently been reported that a high peritoneal transport rate
      was associated with increased mortality in continuous ambulatory peritoneal
      dialysis (CAPD) patients. One possible explanation is that a high peritoneal
      transport rate might be caused by a state of chronic inflammation, which also per
      se might result in increased mortality. Therefore, in this study we investigated
      whether high peritoneal transport rate patients are in a state of chronic
      inflammation. METHODS: The study included 39 clinically stable peritoneal
      dialysis patients (free of peritonitis) who had been on PD for more than 3 months
      (16.8+/-11.8 months). Seven patients were treated with continuous cycling
      peritoneal dialysis (CCPD) and the others were on CAPD. A 4-hour standard
      peritoneal equilibration test (PET) using 2.27% glucose solution was performed in
      each patient. Dialysate samples at 4 hours and blood samples at 2 hours were
      measured for interleukin-1beta (IL-1beta), tumor necrosis
      factor(alpha)(TNFalpha), C-reactive protein (CRP), and hyaluronan as markers of
      inflammation. RESULTS: There was no significant correlation between
      dialysate/plasma (DIP) creatinine (0.82+/-0.15, range 0.51 - 1.15) and blood
      concentrations of IL-1beta (11.2 ng/L, range <5 - 65.9 ng/L),TNFalpha (12.1 ng/L,
      range <5 - 85.4 ng/L), CRP (<10 mg/L, range <10 - 76 mg/L), nor with the blood
      hyaluronan concentration (165 microg/L, range 55 - 955 microg/L). The dialysate
      concentrations of IL-1beta and TNFalpha were below the detectable level in most
      of the samples. Although dialysate hyaluronan concentration (334 microg/L, range
      89 - 1100 microg/L) was correlated with D/P creatinine (r= 0.36, p< 0.05), there
      was no correlation between the total amount of hyaluronan in the effluent and D/P
      creatinine. However, a significant correlation was found between serum hyaluronan
      concentration and glomerular filtration rate (GFR) (r = -0.49, p< 0.005); GFR
      also tended to be correlated with serum TNFalpha (r = -0.31, p = 0.058) but not
      with serum IL-1beta and serum CRP. CONCLUSION: Our results suggest that a high
      peritoneal transport rate is not necessarily related to a state of chronic
      inflammation in CAPD patients. The high mortality rate observed in high
      transporters may relate to other issues, such as fluid balance or abnormal
      nutrition and metabolism, rather than to chronic inflammation.

PMID- 10201337
TI  - Measurement of continuous ambulatory peritoneal dialysis prescription adherence
      using a novel approach.
AB  - OBJECTIVE: The purpose of the study was to test a novel approach to monitoring
      the adherence of continuous ambulatory peritoneal dialysis (CAPD) patients to
      their dialysis prescription. DESIGN: A descriptive observational study was done
      in which exchange behaviors were monitored over a 2-week period of time. SETTING:
      Patients were recruited from an outpatient dialysis center. PARTICIPANTS: A
      convenience sample of patients undergoing CAPD at Piedmont Dialysis Center in
      Winston-Salem, North Carolina was recruited for the study. Of 31 CAPD patients,
      20 (64.5%) agreed to participate. MEASURES: Adherence of CAPD patients to their
      dialysis prescription was monitored using daily logs and an electronic monitoring
      device (the Medication Event Monitoring System, or MEMS; APREX, Menlo Park,
      California, U.S.A.). Patients recorded in their logs their exchange activities
      during the 2-week observation period. Concurrently, patients were instructed to
      deposit the pull tab from their dialysate bag into a MEMS bottle immediately
      after performing each exchange. The MEMS bottle was closed with a cap containing
      a computer chip that recorded the date and time each time the bottle was opened.
      RESULTS: One individual's MEMS device malfunctioned and thus the data presented
      in this report are based upon the remaining 19 patients. A significant
      discrepancy was found between log data and MEMS data, with MEMS data indicating a
      greater number and percentage of missed exchanges. MEMS data indicated that some
      patients concentrated their exchange activities during the day, with shortened
      dwell times between exchanges. Three indices were developed for this study: a
      measure of the average time spent in noncompliance, and indices of consistency in
      the timing of exchanges within and between days. Patients who were defined as
      consistent had lower scores on the noncompliance index compared to patients
      defined as inconsistent (p = 0.015). CONCLUSIONS: This study describes a
      methodology that may be useful in assessing adherence to the peritoneal dialysis
      regimen. Of particular significance is the ability to assess the timing of
      exchanges over the course of a day. Clinical implications are limited due to
      issues of data reliability and validity, the short-term nature of the study, the
      small sample, and the fact that clinical outcomes were not considered in this
      methodology study. Additional research is needed to further develop this data
      collection approach.

PMID- 10201338
TI  - Frequency and causes of discrepancy between Kt/V and creatinine clearance.
AB  - This study examines the frequency of discrepancy between Kt/V urea and creatinine
      clearance (Ccr) measurements in patients on peritoneal dialysis (PD) and the
      reasons for this discrepancy. DESIGN: Nonrandomized, retrospective data analysis.
      SETTING: Single PD unit of a university teaching hospital. PATIENTS: All adult
      patients receiving PD at our center from January 1995 to December 1996. METHODS:
      Actual (a) and desired (d) body weight (BW) were used to calculate urea volume of
      distribution (V) and body surface area (BSA). Patients were divided into four
      groups based upon their total small solute clearances (Kt/V and Ccr, normalized
      by actual weight) and three additional groups based upon actual/desired (a/d)
      body weight ratio. An additional analysis was performed for the subset of anuric
      patients. Data collected for all patients included the following: total Kt, total
      Ccr, 4-hour dialysate/ plasma (D/P) creatinine, serum albumin concentration,
      duration of PD, actual body weight, age, and height. RESULTS: Twenty-three
      percent of the clearance measurements in our study were discrepant, defined as
      having values for either Kt/V or Ccr (but not both) above the accepted targets of
      Kt/V > or = 2.0/wk and Ccr > or = 60 L/wk/ 1.73 m2. Patients with both values
      above target are more likely to have higher residual renal function. Patients who
      are significantly less than BWd and patients on PD for a longer time are more
      likely to have adequate Kt/V but not Ccr. Furthermore, patients who are less than
      90% or greater than 110% of BWd have markedly different values for Kt/V and Ccr
      when BWa versus BWd values are used. CONCLUSIONS: Kt/V and Ccr values are
      frequently discrepant; a number of factors affect these two measurements to
      varying degrees, including weight, degree of residual renal function, and
      duration of PD.

PMID- 10201339
TI  - Tranexamic acid increases peritoneal ultrafiltration volume in patients on CAPD.
AB  - OBJECTIVE: The preservation of ultrafiltration (UF) capacity is crucial to
      maintaining long-term continuous ambulatory peritoneal dialysis (CAPD).The aim of
      the present study was to investigate whether the antiplasmin agent tranexamic
      acid (TNA) increases UF volume in CAPD patients. PATIENTS AND METHODS: Fifteen
      patients on CAPD, 5 with UF loss and 10 without UF loss, were recruited for the
      study. The effect of TNA was evaluated with respect to changes in UF volume,
      peritoneal permeability, peritoneal clearance, bradykinin (BK), and tissue
      plasminogen activator (tPA) concentration. SETTING: Dialysis unit of the
      Saiseikai Central Hospital. RESULTS: In patients with UF loss, 2 weeks of
      treatment with oral TNA produced a significant increase in UF volume in all
      subjects (5/5).TNA also produced a significant increase in peritoneal clearances
      of urea and creatinine (Cr). However, the peritoneal equilibration test (PET)
      revealed that TNA had no effect on dialysate/plasma (D/P) Cr, Kt/V, or the
      protein catabolic rate (PCR).TNA also had no effect on net glucose reabsorption.
      In contrast, significant decreases in BK and blood tPA concentrations in response
      to TNA treatment were noted. BK concentration in drainage fluid was also reduced.
      In the case of patients without UF loss,TNA produced an increase in UF volume in
      70% (7/10). However, no differences were found in blood and drainage BK and tPA
      concentrations between theTNA treatment and nontreatment periods in these
      patients. A comparison of basal BK and tPA concentration showed that there were
      no differences in these parameters between patients with UF loss and those
      without loss of UF. Furthermore,TNA given intraperitoneally to a patient also
      produced a marked increase in UF volume. CONCLUSION: The present study suggests
      thatTNA enhances UF volume in patients both with and without UF loss. SinceTNA
      did not affect peritoneal permeability and glucose reabsorption, the mechanism by
      which TNA exerts an enhancing action on UF is largely unknown. We speculate that
      it may be associated with suppression of the BK and/or tPA system, at least in
      patients with UF loss.

PMID- 10201340
TI  - Analysis of the peritoneal equilibration test in Mexico and factors influencing
      the peritoneal transport rate.
AB  - OBJECTIVE: To validate the peritoneal equilibration test (PET), establish
      reference values in the Mexican population, compare our results with those
      reported by Twardowski et al., and analyze the influence of some factors on the
      peritoneal transport rate (PTR). DESIGN: Retrospective, cross-sectional study.
      PATIENTS: Eighty-six PETs were performed in 45 female and 41 male patients; 35 of
      the patients were diabetics. Creatinine D/P and glucose D/D0 ratios were
      calculated and compared with those from Twardowski et al. In a multivariate
      analysis, age, gender, diabetes mellitus (DM), time on dialysis, and peritonitis
      rate were considered as independent factors influencing the PTR. RESULTS:
      Creatinine D/P and glucose D/D0 ratios at 4 hours were not significantly
      different from those reported by Twardowski et al. Creatinine D/P at 4 hours was
      not different between DM and non-DM patients when the rate of peritonitis and
      time on dialysis were not taken into account. Multivariate analysis did not
      result in any significant model predicting the creatinine D/P at 4 hours.
      CONCLUSIONS: PET validation is reported for the first time in a Latin American
      population. The PET results of this study are similar to those in the literature.
      We found that DM, peritonitis rate, time on dialysis, age, and gender did not
      clearly influence the PTR.

PMID- 10201341
TI  - Comparison of peritoneal fluid culture results from adults and children
      undergoing CAPD.
AB  - BACKGROUND: Peritonitis is a common complication in patients with end-stage renal
      disease treated by continuous ambulatory peritoneal dialysis (CAPD). Empirical
      treatment is based on the organisms that are most frequently isolated and their
      susceptibilities. OBJECTIVE: To analyze and then compare peritoneal fluid culture
      results from adult and pediatric patients on CAPD, with respect to micro
      organisms and antimicrobial susceptibilities. DESIGN: Three-year retrospective
      review of peritoneal fluid cultures from adults and children on CAPD. RESULTS: We
      isolated 481 organisms from 378 peritoneal fluid specimens, collected from 135
      patients (45 children, 90 adults). There were 191 episodes of peritonitis in
      children (mean 4.2+/-3.5, range 1 - 15) compared to 187 in adults (2.1+/-1.9,
      range 1 - 10) (p< 0.001). Two or more episodes occurred in 30 of 45 children
      (67%) compared to 33 of 90 adults (37%) (p < 0.001).The number of different
      organisms/patient as well as the total number of isolates/patient were
      significantly greater in children (respectively, 2.8+/-2.3, range 1 - 12; and
      5.3+/-5.2, range 1 - 27) than in adults (2.0+/-1.3, range 1 - 6; and 2.7+/-2.4,
      range 1 - 10) (p< 0.005). After Staphylococcus epidermidis, S. aureus was the
      most frequently isolated organism, occurring in 18% of episodes in adults and 12%
      of episodes in children (p< 0.01). Twenty-two of 33 fungal isolates (67%) in
      children were Candida parapsilosis compared to 3 of 24 (12%) in adults (p <
      0.001). Subanalysis of multiple episodes revealed that Pseudomonas and Candida
      occurred significantly more often in children (p< 0.01), whereas S. aureus
      occurred more often in adults (p< 0.001). In polymicrobial episodes S.
      epidermidis occurred more often in adults (p < 0.05). Significant differences in
      susceptibilities to ampicillin, ceftriaxone, chloramphenicol, and gentamicin were
      found between children and adults (p< 0.05 - 0.001). CONCLUSIONS: CAPD-associated
      peritonitis occurs significantly more often in children than adults. Significant
      differences in microbial etiology and susceptibilities were found between
      pediatric and adult patients. Each dialysis unit should periodically analyze
      peritoneal fluid culture results from its CAPD patients. These data can then be
      used for optimization of empirical antimicrobial therapy of peritonitis.

PMID- 10201343
TI  - Pharmacokinetics of intermittent intraperitoneal cefazolin in continuous
      ambulatory peritoneal dialysis patients.
AB  - OBJECTIVE: To investigate the pharmacokinetic parameters of intermittent
      intraperitoneal (IP) cefazolin, and recommend a cefazolin dosing regimen in
      continuous ambulatory peritoneal dialysis (CAPD) patients. DESIGN: Prospective
      nonrandomized open study. SETTING: CAPD outpatient clinic in Albany, New York.
      PATIENTS: Seven volunteer CAPD patients without peritonitis. Three of the
      patients were nonanuric while 4 were anuric. INTERVENTIONS: Cefazolin (15 mg/kg
      total body weight) was given to each patient during the first peritoneal
      exchange. Blood and dialysate samples were collected at times 0, 0.5, 1,2,3,6
      (end of the first antibiotic-containing dwell), 24, and 48 hours after the
      administration of IP cefazolin. Urine samples were collected in nonanuric
      patients over the study period. RESULTS: The mean+/-SD amount of cefazolin dose
      absorbed from the dialysate after the 6-hour dwell was 69.7%+/-8.0% of the
      administered dose. The cefazolin absorption rate constant from dialysate to serum
      was 0.21+/-0.1/hr (absorption half-life 3.5+/-0.8 hr). The mean serum
      concentrations reached at 24 and 48 hours were 52.4+/-3.7 mg/L and 30.3+/-5.9
      mg/L, respectively. The mean dialysate cefazolin concentrations reached at 24 and
      48 hours were 15.1+/-3.4 mg/L and 7.9+/-1.4 mg/L, respectively. The cefazolin
      serum elimination rate constant was 0.02+/-0.01/hr (elimination half-life 31.5+/
      8.8 hr). The total cefazolin body clearance was 3.4+/-0.6 ml/min. In the 3
      nonanuric patients the mean renal clearance of cefazolin was 0.6+/-0.4 ml/min.
      The peritoneal clearance of cefazolin was 1.0+/-0.3 mL/min. The systemic volume
      of distribution of cefazolin was 0.2+/-0.05 L/kg. No statistical difference was
      detected in pharmacokinetic parameters between anuric and nonanuric patients,
      although this may be due to the small number of patients in each group.
      CONCLUSION: A single daily dose of cefazolin dosed at 15 mg/kg actual body weight
      in CAPD patients is effective in achieving serum concentration levels greater
      than the minimum inhibitory concentration for sensitive organisms over 48 hours,
      and dialysate concentration levels over 24 hours. Caution is warranted in
      extrapolation of dosing recommendations to patients who maintain a significant
      degree of residual renal function.

PMID- 10201342
TI  - The standard peritoneal permeability analysis in the rabbit: a longitudinal model
      for peritoneal dialysis.
AB  - OBJECTIVE: The development of an experimental peritoneal dialysis (PD) model in
      rabbits to investigate peritoneal transport characteristics during a longitudinal
      follow-up and to assess normal values of these peritoneal transport parameters.
      DESIGN: Peritoneal transport parameters were determined in conscious,
      unrestrained rabbits by standard peritoneal permeability analysis adjusted for
      rabbits (SPAR). In this test a 1-hour dwell with 3.86% glucose dialysate is used.
      Dextran 70 (1g/L) was added to the dialysate to allow calculation of fluid
      kinetics. Dialysate samples were taken before, 10, and 40 minutes after
      instillation and at the end of the dwell. Blood was drawn at the end of the
      dwell. EXPERIMENTAL ANIMALS: Eighteen female New Zealand White rabbits (2565 g)
      were included for catheter implantation. SPARs were performed in 15 animals; the
      other 3 were excluded due to complications. MAIN OUTCOME: The mass transfer area
      coefficients (MTACs) of the low molecular weight solutes urea (MTAC(urea)) and
      creatinine (MTACcr) were calculated. The clearances of albumin (CIalb) and IgG
      (CI(IgG)), glucose absorption, and fluid transport were computed. Coefficients of
      intraindividual variation (Vc) were calculated for these parameters. RESULTS: The
      main complications were catheter obstruction and/or dislocation. Five rabbits
      underwent uncomplicated PD during a 4-week period. Fifteen SPARs in 15 stable
      rabbits were performed and analyzed to obtain normal values. Means and standard
      deviations of the transport parameters were as follows: MTAC(urea) 2.24+/-0.57
      mL/min, MTACcr 1.61+/-0.30 mU/min, CI(alb) 52.9+/-17.2 microL/min, CI(IgG) 44.5+/
      22.9 UL/min. The transcapillary ultrafiltration rate was 0.66+/-0.13 mL/min and
      the lymphatic absorption rate 0.47+/-0.26 mL/min. The parameters of solute
      transport were upscaled to those in humans using two different methods. MTACs of
      low molecular weight solutes in rabbits and patients were of the same order of
      magnitude, but the clearance of albumin was approximately four times higher in
      rabbits than in patients, and that of IgG eight times. In all rabbits sieving of
      sodium was observed. The dialysate/plasma (D/P) of sodium decreased to a minimum
      at 40 min (p<0.003 vs the initial value), followed by a rise to 60 min. The
      minimal value was 0.884+/-0.002. The coefficients of variation calculated on 7
      rabbits that underwent two or more SPARs were similar to those assessed from the
      patient data. This indicates stability of the model and reproducibility of the
      SPAR. CONCLUSION: The conscious rabbit model for PD can be used for repeated
      studies on peritoneal transport.

PMID- 10201344
TI  - Polyester mesh repair of pericatheter fluid leak in CAPD patients: report of two
      cases.

PMID- 10201345
TI  - Longitudinal changes in peritoneal membrane transport kinetics in normal rats.

PMID- 10201346
TI  - Residual proteinuria in CAPD diminishes the value of serum albumin in audit.

PMID- 10201348
TI  - An important differential diagnosis in CAPD patients with sudden onset of fever,
      vomiting, abdominal pain, and cloudy dialysate.

PMID- 10201347
TI  - The effect of oral protein supplements on the nutritional status of malnourished
      CAPD patients.

PMID- 10201349
TI  - Uremic cirrhotic CAPD patient with gastric carcinoma.

PMID- 10201350
TI  - Campylobacter jejuni II peritonitis in a CCPD patient: cure by oral
      clarithromycin.

PMID- 10201351
TI  - Effect of age on normalized small solute clearances in men on peritoneal
      dialysis.

PMID- 10201352
TI  - Rectus sheath hematoma/abscess following acute peritoneal dialysis.

PMID- 10201353
TI  - Initial treatment of CAPD peritonitis: poor response with association of
      cefazolin and amikacin.

PMID- 10201354
TI  - No difference in plasma fibrinogen levels between CAPD patients taking
      atorvastatin and simvastatin.

PMID- 10201355
TI  - Literature. January-February 1999.

PMID- 10201356
TI  - Business and pleasure can mix.

PMID- 10201357
TI  - Wellcome wages battle to house companies next to genome labs.

PMID- 10201358
TI  - New Howard Hughes head seeks bioinformatics boost.

PMID- 10201359
TI  - Court suspends pioneering gene deal in Yellowstone.

PMID- 10201361
TI  - Biotech industry seeks 'honest brokers'.

PMID- 10201360
TI  - US concern grows over secrecy clauses.

PMID- 10201362
TI  - Women scientists unite to battle cowboy culture.

PMID- 10201363
TI  - Phage-lift for game theory.

PMID- 10201364
TI  - Developmental biology. A unity of opposites.

PMID- 10201365
TI  - Microbiology. Millennium bug.

PMID- 10201366
TI  - Sugars slide into heparin activity.

PMID- 10201367
TI  - Gertrude Belle Elion (1918-99)

PMID- 10201368
TI  - Angiogenesis inhibited by drinking tea.

PMID- 10201369
TI  - Molecular basis of triclosan activity.

PMID- 10201370
TI  - Electrical conduction through DNA molecules.
AB  - The question of whether DNA is able to transport electrons has attracted much
      interest, particularly as this ability may play a role as a repair mechanism
      after radiation damage to the DNA helix. Experiments addressing DNA conductivity
      have involved a large number of DNA strands doped with intercalated donor and
      acceptor molecules, and the conductivity has been assessed from electron transfer
      rates as a function of the distance between the donor and acceptor sites. But the
      experimental results remain contradictory, as do theoretical predictions. Here we
      report direct measurements of electrical current as a function of the potential
      applied across a few DNA molecules associated into single ropes at least 600 nm
      long, which indicate efficient conduction through the ropes. We find that the
      resistivity values derived from these measurements are comparable to those of
      conducting polymers, and indicate that DNA transports electrical current as
      efficiently as a good semiconductor. This property, and the fact that DNA
      molecules of specific composition ranging in length from just a few nucleotides
      to chains several tens of micrometres long can be routinely prepared, makes DNA
      ideally suited for the construction of mesoscopic electronic devices.

PMID- 10201371
TI  - Synthesis of thrombin-inhibiting heparin mimetics without side effects.
AB  - Unwanted side effects of pharmacologically active compounds can usually be
      eliminated by structural modifications. But the complex heterogeneous structure
      of the polysaccharide heparin has limited this approach to fragmentation, leading
      to slightly better-tolerated heparin preparations of low molecular mass. Despite
      this improvement, heparin-induced thrombocytopaenia (HIT), related to an
      interaction with platelet factor 4 (PF4) and, to a lesser extent, haemorrhages,
      remain significant side effects of heparinotherapy. Breakthroughs in
      oligosaccharide chemistry made possible the total synthesis of the
      pentasaccharide antithrombin-binding site of heparin. This pentasaccharide
      represents a new family of potential antithrombotic drugs, devoid of thrombin
      inhibitory properties, and free of undesired interactions with blood and vessel
      components. To obtain more potent and well-tolerated antithrombotic drugs, we
      wished to synthesize heparin mimetics able to inhibit thrombin, that is, longer
      oligosaccharides. Like thrombin inhibition, undesired interactions are directly
      correlated to the charge and the size of the molecules, so we had to design
      structures that were able to discriminate between thrombin and other proteins,
      particularly PF4. Here we describe the use of multistep converging synthesis to
      obtain sulphated oligosaccharides that meet these requirements.

PMID- 10201372
TI  - Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells.
AB  - Mutations in the adenomatous polyposis coli (APC) tumour-suppressor gene occur in
      most human colon cancers. Loss of functional APC protein results in the
      accumulation of beta-catenin. Mutant forms of beta-catenin have been discovered
      in colon cancers that retain wild-type APC genes, and also in melanomas,
      medulloblastomas, prostate cancer and gastric and hepatocellular carcinomas. The
      accumulation of beta-catenin activates genes that are responsive to transcription
      factors of the TCF/LEF family, with which beta-catenin interacts. Here we show
      that beta-catenin activates transcription from the cyclin D1 promoter, and that
      sequences within the promoter that are related to consensus TCF/LEF-binding sites
      are necessary for activation. The oncoprotein p21ras further activates
      transcription of the cyclin D1 gene, through sites within the promoter that bind
      the transcriptional regulators Ets or CREB. Cells expressing mutant beta-catenin
      produce high levels of cyclin D1 messenger RNA and protein constitutively.
      Furthermore, expression of a dominant-negative form of TCF in colon-cancer cells
      strongly inhibits expression of cyclin D1 without affecting expression of cyclin
      D2, cyclin E, or cyclin-dependent kinases 2, 4 or 6. This dominant-negative TCF
      causes cells to arrest in the G1 phase of the cell cycle; this phenotype can be
      rescued by expression of cyclin D1 under the cytomegalovirus promoter. Abnormal
      levels of beta-catenin may therefore contribute to neoplastic transformation by
      causing accumulation of cyclin D1.

PMID- 10201373
TI  - Local inhibition and long-range enhancement of Dpp signal transduction by Sog.
AB  - Extracellular gradients of signalling molecules can specify different thresholds
      of gene activity in development. A gradient of Decapentaplegic (Dpp) activity
      subdivides the dorsal ectoderm of the Drosophila embryo into amnioserosa and
      dorsal epidermis. The proteins Short gastrulation (Sog) and Tolloid (Tld) are
      required to shape this gradient. Sog has been proposed to form an inhibitory
      complex with either Dpp or the related ligand Screw, and is subsequently
      processed by the protease Tld. Paradoxically, Sog appears to be required for
      amnioserosa formation, which is specified by peak Dpp signalling activity. Here
      we show that the misexpression of sog using the even-skipped stripe-2 enhancer
      redistributes Dpp signalling in a mutant background in which dpp is expressed
      throughout the embryo. Dpp activity is diminished near the Sog stripe and peak
      Dpp signalling is detected far from this stripe. However, a tethered form of Sog
      suppresses local Dpp activity without augmenting Dpp activity at a distance,
      indicating that diffusion of Sog may be required for enhanced Dpp activity and
      consequent amnioserosa formation. The long-distance stimulation of Dpp activity
      by Sog requires Tld, whereas Sog-mediated inhibition of Dpp does not. The
      heterologous Dpp inhibitor Noggin inhibits Dpp signalling but fails to augment
      Dpp activity. These results suggest an unusual strategy for generating a gradient
      threshold of growth-factor activity, whereby Sog and its protease specify peak
      Dpp signalling far from a localized source of Sog.

PMID- 10201374
TI  - A new secreted protein that binds to Wnt proteins and inhibits their activities.
AB  - The Wnt proteins constitute a large family of extracellular signalling molecules
      that are found throughout the animal kingdom and are important for a wide variety
      of normal and pathological developmental processes. Here we describe Wnt
      inhibitory factor-1 (WIF-1), a secreted protein that binds to Wnt proteins and
      inhibits their activities. WIF-1 is present in fish, amphibia and mammals, and is
      expressed during Xenopus and zebrafish development in a complex pattern that
      includes paraxial presomitic mesoderm, notochord, branchial arches and neural
      crest derivatives. We use Xenopus embryos to show that WIF-1 overexpression
      affects somitogenesis (the generation of trunk mesoderm segments), in agreement
      with its normal expression in paraxial mesoderm. In vitro, WIF-1 binds to
      Drosophila Wingless and Xenopus Wnt8 produced by Drosophila S2 cells. Together
      with earlier results obtained with the secreted Frizzled-related proteins, our
      results indicate that Wnt proteins interact with structurally diverse
      extracellular inhibitors, presumably to fine-tune the spatial and temporal
      patterns of Wnt activity.

PMID- 10201375
TI  - A capsaicin-receptor homologue with a high threshold for noxious heat.
AB  - Pain-producing heat is detected by several classes of nociceptive sensory neuron
      that differ in their thermal response thresholds. The cloned capsaicin receptor,
      also known as the vanilloid receptor subtype 1 (VR1), is a heat-gated ion channel
      that has been proposed to mediate responses of small-diameter sensory neurons to
      moderate (43 degrees C) thermal stimuli. VR1 is also activated by protons,
      indicating that it may participate in the detection of noxious thermal and
      chemical stimuli in vivo. Here we identify a structurally related receptor, VRL
      1, that does not respond to capsaicin, acid or moderate heat. Instead, VRL-1 is
      activated by high temperatures, with a threshold of approximately 52 degrees C.
      Within sensory ganglia, VRL-1 is most prominently expressed by a subset of medium
      to large-diameter neurons, making it a candidate receptor for transducing high
      threshold heat responses in this class of cells. VRL-1 transcripts are not
      restricted to the sensory nervous system, indicating that this channel may be
      activated by stimuli other than heat. We propose that responses to noxious heat
      involve these related, but distinct, ion-channel subtypes that together detect a
      range of stimulus intensities.

PMID- 10201376
TI  - Prisoner's dilemma in an RNA virus.
AB  - The evolution of competitive interactions among viruses was studied in the RNA
      phage phi6 at high and low multiplicities of infection (that is, at high and low
      ratios of infecting phage to host cells). At high multiplicities, many phage
      infect and reproduce in the same host cell, whereas at low multiplicities the
      viruses reproduce mainly as clones. An unexpected result of this study was that
      phage grown at high rates of co-infection increased in fitness initially, but
      then evolved lowered fitness. Here we show that the fitness of the high
      multiplicity phage relative to their ancestors generates a pay-off matrix
      conforming to the prisoner's dilemma strategy of game theory. In this strategy,
      defection (selfishness) evolves, despite the greater fitness pay-off that would
      result if all players were to cooperate. Viral cooperation and defection can be
      defined as, respectively, the manufacturing and sequestering of diffusible
      (shared) intracellular products. Because the low-multiplicity phage did not
      evolve lowered fitness, we attribute the evolution of selfishness to the lack of
      clonal structure and the mixing of unrelated genotypes at high multiplicity.

PMID- 10201377
TI  - Stability offers unique opportunity for research.

PMID- 10201378
TI  - Scientists seek support from Mexican public.

PMID- 10201379
TI  - Customs delays drive researchers to smuggling.

PMID- 10201381
TI  - Andes observatories belatedly take root.

PMID- 10201380
TI  - Chile tries to bridge gap in scientific standards.

PMID- 10201382
TI  - Community split on Peronist reform effort.

PMID- 10201383
TI  - Collapse of real sharpens Brazil's contrasts.

PMID- 10201384
TI  - Brazil's space programme comes of age.

PMID- 10201385
TI  - Resources lacking to save Amazon biodiversity.

PMID- 10201386
TI  - Cuban biotechnology treads a lonely path.

PMID- 10201387
TI  - How folate fights disease.

PMID- 10201388
TI  - The best offense is a good defense.

PMID- 10201389
TI  - Structural basis of Hox specificity.

PMID- 10201390
TI  - Switching affinities in nuclear trafficking.

PMID- 10201391
TI  - Folding under the influence.

PMID- 10201392
TI  - First molecular explanation of disease.

PMID- 10201393
TI  - Alternative metal-binding sites in rubrerythrin.

PMID- 10201394
TI  - Picture story. Move over and bind.

PMID- 10201395
TI  - E-cadherin functions as a cis-dimer at the cell-cell adhesive interface in vivo.

PMID- 10201396
TI  - Structure of the cell-adhesion fragment of intimin from enteropathogenic
      Escherichia coli.
AB  - Enteropathogenic Escherichia coli (EPEC) induce gross cytoskeletal rearrangement
      within epithelial cells, immediately beneath the attached bacterium. The C
      terminal 280 amino acid residues of intimin (Int280; 30.1 kDa), a bacterial cell
      adhesion molecule, mediate the intimate bacterial host-cell interaction.
      Recently, interest in this process has been stimulated by the discovery that the
      bacterial intimin receptor protein (Tir) is translocated into the host cell
      membrane, phosphorylated, and after binding intimin triggers the intimate
      attachment. Using multidimensional nuclear magnetic resonance (NMR) and combining
      perdeuteration with site-specific protonation of methyl groups, we have
      determined the global fold of Int280. This represents one of the largest, non
      oligomeric protein structures to be determined by NMR that has not been
      previously resolved by X-ray crystallography. Int280 comprises three domains; two
      immunoglobulin-like domains and a C-type lectin-like module, which define a new
      family of bacterial adhesion molecules. These findings also imply that
      carbohydrate recognition may be important in intimin-mediated cell adhesion.

PMID- 10201397
TI  - A new metal ion interaction in the Tetrahymena ribozyme reaction revealed by
      double sulfur substitution.
AB  - The Tetrahymena ribozyme is a metalloenzyme that catalyzes cleavage of
      oligonucleotide substrates by phosphoryl transfer. Thiophilic metal ions such as
      Mn2+, Zn2+ or Cd2+ rescue the >10(3)-fold inhibitory effect of sulfur
      substitution of the 3'-oxygen leaving group but do not effectively rescue the
      effect of sulfur substitution of the nonbridging pro-Sp phosphoryl oxygen. We now
      show that the latter effect can be fully rescued by Zn2+ or Cd2+ using a
      phosphorodithioate substrate, in which both the 3'-oxygen and the pro-Sp oxygen
      are simultaneously substituted with sulfur. These results provide the first
      functional evidence that metallophosphotransferases can mediate catalysis via
      metal ion coordination to both the leaving group and a nonbridging oxygen of the
      scissile phosphate.

PMID- 10201398
TI  - Quaternary changes in topoisomerase II may direct orthogonal movement of two DNA
      strands.
AB  - Type II DNA topoisomerases mediate the passage of one DNA duplex through a
      transient break in another, an event essential for chromosome segregation and
      cell viability. The active sites of the type II topoisomerase dimer associate
      covalently with the DNA break-points and must separate by at least the width of
      the second DNA duplex to accommodate transport. A new structure of the
      Saccharomyces cerevisiae topoisomerase II DNA-binding and cleavage core suggests
      that in addition to conformational changes in the DNA-opening platform, a
      dramatic reorganization of accessory domains may occur during catalysis. These
      conformational differences have implications for both the DNA-breaking and duplex
      transport events in the topo II reaction mechanism, suggest a mechanism by which
      two distinct drug-resistance loci interact, and illustrate the scope of
      structural changes in the cycling of molecular machines.

PMID- 10201399
TI  - Crystal structure of the N-terminal, growth factor-like domain of Alzheimer
      amyloid precursor protein.
AB  - Amyloid precursor protein (APP) plays a central role in Alzheimer disease. A
      proteolytic-breakdown product of APP, called beta-amyloid, is a major component
      of the diffuse and fibrillar deposits found in Alzheimer diseased brains. The
      normal physiological role of APP remains largely unknown despite much work. A
      knowledge of its function will not only provide insights into the genesis of the
      disease but may also prove vital in the development of an effective therapy. Here
      we describe the 1.8 A resolution crystal structure of the N-terminal, heparin
      binding domain of APP (residues 28-123), which is responsible, among other
      things, for stimulation of neurite outgrowth. The structure reveals a highly
      charged basic surface that may interact with glycosaminoglycans in the brain and
      an abutting hydrophobic surface that is proposed to play an important functional
      role such as dimerization or ligand binding. Structural similarities with
      cysteine-rich growth factors, taken together with its known growth-promoting
      properties, suggests the APP N-terminal domain could function as a growth factor
      in vivo.

PMID- 10201400
TI  - A cis proline turn linking two beta-hairpin strands in the solution structure of
      an antibody-bound HIV-1IIIB V3 peptide.
AB  - The refined solution structure of an 18-residue HIV-1IIIB V3 peptide in complex
      with the Fv fragment of an anti-gp120 antibody reveals an unexpected type VI beta
      turn comprising residues RGPG at the center of a beta-hairpin. The central
      glycine and proline of this turn are linked by a cis peptide bond. The residues
      of the turn interact extensively with the antibody Fv. 15N[1H] NOE measurements
      show that the backbone of the peptide, including the central QRGPGR loop, is well
      ordered in the complex. The solution structure is significantly different from
      the X-ray structures of HIV-1MN V3 peptides bound to anti-peptide antibodies.
      These differences could be due to a two-residue (QR) insertion preceding the GPGR
      sequence in the HIV-1IIIB strain, and the much longer peptide epitope immobilized
      by the anti-gp120 antibody.

PMID- 10201401
TI  - Pilus chaperone FimC-adhesin FimH interactions mapped by TROSY-NMR.
AB  - The 23 kDa two-domain periplasmic chaperone FimC from Escherichia coli is
      required for the assembly of type-1 pili, which are filamentous, highly
      oligomeric protein complexes anchored to the outer bacterial membrane that
      mediate adhesion of pathogenic E. coli strains to host cell surfaces. Here we
      identified the contact sites on the surface of the NMR structure of FimC that are
      responsible for the binding of the 28 kDa mannose-binding type-1 pilus subunit
      FimH by 15N and 1H NMR chemical shift mapping, using transverse relaxation
      optimized spectroscopy (TROSY). The FimH-binding surface of FimC is formed nearly
      entirely by the N-terminal domain, and its extent and shape indicate that FimC
      binds a folded form of the pilus subunits.

PMID- 10201402
TI  - Crystal structure of brefeldin A esterase, a bacterial homolog of the mammalian
      hormone-sensitive lipase.
AB  - Brefeldin A esterase (BFAE), a detoxifying enzyme isolated from Bacillus
      subtilis, hydrolyzes and inactivates BFA, a potent fungal inhibitor of
      intracellular vesicle-dependent secretory transport and poliovirus RNA
      replication. We have solved the crystal structure of BFAE and we discovered that
      the previously reported amino acid sequence was in serious error due to frame
      shifts in the cDNA sequence. The correct sequence, inferred from the
      experimentally phased electron density map, revealed that BFAE is a homolog of
      the mammalian hormone sensitive lipase (HSL). It is a canonical alpha/beta
      hydrolase with two insertions forming the substrate binding pocket. The enzyme
      contains a lipase-like catalytic triad, Ser 202, Asp 308 and His 338, consistent
      with mutational studies that implicate the homologous Ser 424, Asp 693 and His
      723 in the catalytic triad in human HSL.

PMID- 10201403
TI  - Sequence-dependent mechanics of single DNA molecules.
AB  - Atomic force microscope-based single-molecule force spectroscopy was employed to
      measure sequence-dependent mechanical properties of DNA by stretching individual
      DNA double strands attached between a gold surface and an AFM tip. We discovered
      that in lambda-phage DNA the previously reported B-S transition, where 'S'
      represents an overstretched conformation, at 65 pN is followed by a
      nonequilibrium melting transition at 150 pN. During this transition the DNA is
      split into single strands that fully recombine upon relaxation. The sequence
      dependence was investigated in comparative studies with poly(dG-dC) and poly(dA
      dT) DNA. Both the B-S and the melting transition occur at significantly lower
      forces in poly(dA-dT) compared to poly(dG-dC). We made use of the melting
      transition to prepare single poly(dG-dC) and poly(dA-dT) DNA strands that upon
      relaxation reannealed into hairpins as a result of their self-complementary
      sequence. The unzipping of these hairpins directly revealed the base pair
      unbinding forces for G-C to be 20 +/- 3 pN and for A-T to be 9 +/- 3 pN.

PMID- 10201404
TI  - Is cooperative oxygen binding by hemoglobin really understood?
AB  - The enormous success of structural biology challenges the physical scientist. Can
      biophysical studies provide a truly deeper understanding of how a protein works
      than can be obtained from static structures and qualitative analysis of
      biochemical data? We address this question in a case study by presenting the key
      concepts and experimental results that have led to our current understanding of
      cooperative oxygen binding by hemoglobin, the paradigm of structure function
      relations in multisubunit proteins. We conclude that the underlying simplicity of
      the two-state allosteric mechanism could not have been demonstrated without novel
      physical experiments and a rigorous quantitative analysis.

PMID- 10201405
TI  - The structure and properties of methylenetetrahydrofolate reductase from
      Escherichia coli suggest how folate ameliorates human hyperhomocysteinemia.
AB  - Elevated plasma homocysteine levels are associated with increased risk for
      cardiovascular disease and neural tube defects in humans. Folate treatment
      decreases homocysteine levels and dramatically reduces the incidence of neural
      tube defects. The flavoprotein methylenetetrahydrofolate reductase (MTHFR) is a
      likely target for these actions of folate. The most common genetic cause of
      mildly elevated plasma homocysteine in humans is the MTHFR polymorphism A222V
      (base change C677-->T). The X-ray analysis of E. coli MTHFR, reported here,
      provides a model for the catalytic domain that is shared by all MTHFRs. This
      domain is a beta8alpha8 barrel that binds FAD in a novel fashion. Ala 177,
      corresponding to Ala 222 in human MTHFR, is near the bottom of the barrel and
      distant from the FAD. The mutation A177V does not affect Km or k(cat) but instead
      increases the propensity for bacterial MTHFR to lose its essential flavin
      cofactor. Folate derivatives protect wild-type and mutant E. coli enzymes against
      flavin loss, and protect human MTHFR and the A222V mutant against thermal
      inactivation, suggesting a mechanism by which folate treatment reduces
      homocysteine levels.

PMID- 10201406
TI  - NMR structure of the Tn916 integrase-DNA complex.
AB  - The integrase protein catalyzes the excision and integration of the Tn916
      conjugative transposon, a promiscuous genetic element that spreads antibiotic
      resistance in pathogenic bacteria. The solution structure of the N-terminal
      domain of the Tn916 integrase protein bound to its DNA-binding site within the
      transposon arm has been determined. The structure reveals an interesting mode of
      DNA recognition, in which the face of a three-stranded antiparallel beta-sheet is
      positioned within the major groove. A comparison to the structure of the homing
      endonuclease I-Ppol-DNA complex suggests that the three-stranded sheet may
      represent a new DNA-binding motif whose residue composition and position within
      the major groove are varied to alter specificity. The structure also provides
      insights into the mechanism of conjugative transposition. The DNA in the complex
      is bent approximately 35 degrees and may, together with potential interactions
      between bound integrase proteins at directly repeated sites, significantly bend
      the arms of the transposon.

PMID- 10201408
TI  - Acceleration of the folding of acylphosphatase by stabilization of local
      secondary structure.
AB  - The addition of trifluoroethanol or hexafluoroisopropanol converts the apparent
      two-state folding of acylphosphatase, a small alpha/beta protein, into a
      multistate mechanism where secondary structure accumulates significantly in the
      denatured state before folding to the native state. This results in a marked
      acceleration of folding as revealed by following the intrinsic fluorescence and
      circular dichroism changes upon folding. The folding rate is at a maximum when
      the secondary-structure content of the denatured state corresponds to that of the
      native state, while further stabilization of secondary structure decreases the
      folding rate. These findings indicate that stabilization of intermediate
      structure can either enhance or retard folding depending on its nature and
      content of native-like interactions.

PMID- 10201407
TI  - Structures of the M2 channel-lining segments from nicotinic acetylcholine and
      NMDA receptors by NMR spectroscopy.
AB  - The structures of functional peptides corresponding to the predicted channel
      lining M2 segments of the nicotinic acetylcholine receptor (AChR) and of a
      glutamate receptor of the NMDA subtype (NMDAR) were determined using solution NMR
      experiments on micelle samples, and solid-state NMR experiments on bilayer
      samples. Both M2 segments form straight transmembrane alpha-helices with no
      kinks. The AChR M2 peptide inserts in the lipid bilayer at an angle of 12 degrees
      relative to the bilayer normal, with a rotation about the helix long axis such
      that the polar residues face the N-terminal side of the membrane, which is
      assigned to be intracellular. A model built from these solid-state NMR data, and
      assuming a symmetric pentameric arrangement of M2 helices, results in a funnel
      like architecture for the channel, with the wide opening on the N-terminal
      intracellular side.

PMID- 10201409
TI  - Autoinhibition by an internal nuclear localization signal revealed by the crystal
      structure of mammalian importin alpha.
AB  - Importin alpha is the nuclear import receptor that recognizes classical
      monopartite and bipartite nuclear localization signals (NLSs). The structure of
      mouse importin alpha has been determined at 2.5 A resolution. The structure shows
      a large C-terminal domain containing armadillo repeats, and a less structured N
      terminal importin beta-binding domain containing an internal NLS bound to the NLS
      binding site. The structure explains the regulatory switch between the
      cytoplasmic, high-affinity form, and the nuclear, low-affinity form for NLS
      binding of the nuclear import receptor predicted by the current models of nuclear
      import. Importin beta conceivably converts the low- to high-affinity form by
      binding to a site overlapping the autoinhibitory sequence. The structure also has
      implications for understanding NLS recognition, and the structures of armadillo
      and HEAT repeats.

PMID- 10201410
TI  - Health outcome measures.

PMID- 10201412
TI  - Influence of clinical and demographic variables on quality of life in patients
      with Parkinson's disease.
AB  - OBJECTIVES: To identify the clinical and demographic factors that are associated
      with a poor quality of life in patients with Parkinson's disease. METHODS: 233 of
      a total of 245 patients identified in a community based study in a Norwegian
      county participated in the study. Quality of life was measured by the Nottingham
      Health Profile (NHP). The results were compared with those in 100 healthy elderly
      people. Clinical and demographic variables were determined during a
      semistructured interview and by clinical examination by a neurologist. Multiple
      regression analyses were used to determine which variables were associated with
      higher distress scores. RESULTS: Patients with Parkinson's disease had higher
      distress scores than the healthy elderly people for all the NHP dimensions. The
      variables that most strongly predicted a high total NHP score were depressive
      symptoms, self reported insomnia, and a low degree of independence, measured by
      the Schwab and England scale. Severity of parkinsonism contributed, but to a
      lesser extent. Nearly half the patients with Parkinson's disease reported lack of
      energy, compared with a fifth of the control group. Severity of depressive
      symptoms and a higher score on the UPDRS motor subscale only partly accounted for
      this finding. Only 30% of the variation in NHP energy score was explained by the
      predictive variables identified in this study. CONCLUSIONS: Parkinson's disease
      has a substantial impact on health related quality of life. Depressive symptoms
      and sleep disorders correlated strongly with high distress scores. Patients with
      Parkinson's disease should be examined for both conditions, which require
      treatment. Low energy was commonly reported and may be a separate entity of
      Parkinson's disease.

PMID- 10201411
TI  - Neurology and the skin.
AB  - As knowledge of pathophysiology grows, so does the refinement of diagnoses.
      Sometimes increased knowledge permits consolidation and unification.
      Unfortunately, at our present level of understanding, it usually demands
      proliferation of diagnostic categories. As tedious as this diagnostic splintering
      may seem, such is the price currently exacted of both the investigator and the
      clinician who seek to optimise management. Increased diagnostic refinement often
      requires inquiry into matters outside the bounds of one's specialty. Most often
      we turn to the radiologist or to the laboratory to narrow the differential
      diagnosis generated from the history and neurological examination. As we have
      shown, a useful intermediate step is extension of the physical examination to
      organs such as the skin, which are not the traditional preserve of the
      neurologist. That any text could confer the sophistication required for expert
      dermatological diagnosis is an unrealistic expectation. However, we hope that
      this review will encourage careful examination of the skin, hair, and nails by
      the neurological practitioner, with consideration of referral to a dermatologist
      when greater expertise is required.

PMID- 10201413
TI  - Efficacy, safety, and tolerance of the non-ergoline dopamine agonist pramipexole
      in the treatment of advanced Parkinson's disease: a double blind, placebo
      controlled, randomised, multicentre study.
AB  - OBJECTIVES: Pramipexole, a non-ergot dopamine D2/D3 receptor agonist, was
      investigated as an add on drug in advanced parkinsonian patients with motor
      fluctuations to assess efficacy, safety, and tolerance. METHODS: Seventy eight
      patients of either sex with advanced Parkinson's disease and treatment
      complications such as motor fluctuations were enrolled into a double blind,
      placebo controlled, randomised, multicentre study (phase II) and assigned to add
      on treatment with pramipexole (n=34) versus placebo (n=44) to a previously
      stabilised antiparkinsonian medication (7 week dose titration interval, 4 week
      maintenance period). The primary end point of efficacy was the change from
      baseline in the total score of the unified Parkinson's disease rating scale
      (UPDRS) in the on "period" (2 hours after intake of study medication). Safety and
      tolerability were assessed on the basis of adverse events, vital signs,
      laboratory measurements, and ECG recordings. RESULTS: There was a significant
      improvement of the pramipexole group in UPDRS total scores, subscores part II,
      III (activities of daily living and motor examination), and IV (complications of
      therapy). Mean UPDRS total score decreased by 37.3% under pramipexole compared
      with 12.2% under placebo (p<0.001). Patients under pramipexole reported an
      overall reduction in "off" periods of 12%--resulting in 1.7 more hours "on" time
      a day--compared with an increase in "off" periods of 2% under placebo. There were
      no unexpected safety results. The adverse event profile disclosed a high
      tolerability. The most important adverse events under pramipexole were fatigue,
      dyskinesia, and vivid dreams. CONCLUSION: Pramipexole administration is an
      efficacious and well tolerated add on therapy in patients with advanced
      Parkinson's disease with an improvement in activities of daily living, motor
      function, and treatment associated complications.

PMID- 10201414
TI  - Impairment of EEG desynchronisation before and during movement and its relation
      to bradykinesia in Parkinson's disease.
AB  - OBJECTIVE: It has been suggested that the basal ganglia act to release cortical
      elements from idling (alpha) rhythms so that they may become coherent in the
      gamma range, thereby binding together those distributed activities necessary for
      the effective selection and execution of a motor act. This hypothesis was tested
      in 10 patients with idiopathic Parkinson's disease. METHODS: Surface EEG was
      recorded during self paced squeezing of the hand and elbow flexion performed
      separately, simultaneously, or sequentially. Recordings were made after overnight
      withdrawal of medication and, again, 1 hour after levodopa. The medication
      related improvement in EEG desynchronisation (in the 7.5-12.5 Hz band) over the 1
      second before movement and during movement were separately correlated with the
      improvement in movement time for each electrode site. Correlation coefficients
      (r) > 0.632 were considered significant (p<0.05). RESULTS: Improvement in
      premovement desynchronisation correlated with reduction in bradykinesia over the
      contralateral sensorimotor cortex and supplementary motor area in flexion and
      squeeze, respectively. However, when both movements were combined either
      simultaneously or sequentially, this correlation shifted anteriorly, to areas
      overlying prefrontal cortex. Improvement in EEG desynchronisation during movement
      only correlated with reduction in bradykinesia in two tasks. Correlation was seen
      over the supplementary motor area during flexion, and central prefrontal and
      ipsilateral premotor areas during simultaneous flex and squeeze. CONCLUSIONS: The
      results are consistent with the idea that the basal ganglia liberate frontal
      cortex from idling rhythms, and that this effect is focused and specific in so
      far as it changes with the demands of the task. In particular, the effective
      selection and execution of more complex tasks is associated with changes over the
      prefrontal cortex.

PMID- 10201415
TI  - EMG responses to free fall in elderly subjects and akinetic rigid patients.
AB  - OBJECTIVES: The EMG startle response to free fall was studied in young and old
      normal subjects, patients with absent vestibular function, and patients with
      akinetic-rigid syndromes. The aim was to detect any derangement in this early
      phase of the "landing response" in patient groups with a tendency to fall. In
      normal subjects the characteristics of a voluntary muscle contraction (tibialis
      anterior) was also compared when evoked by a non-startling sound and by the free
      fall startle. METHODS: Subjects lay supine on a couch which was unexpectedly
      released into free fall. Latencies of multiple surface EMG recordings to the
      onset of free fall, detected by a head mounted linear accelerometer, were
      measured. RESULTS AND CONCLUSIONS: (1) EMG responses in younger normal subjects
      occurred at: sternomastoid 54 ms, abdominals 69 ms, quadriceps 78 ms, deltoid 80
      ms, and tibialis anterior 85 ms. This pattern of muscle activation, which is not
      a simple rostrocaudal progression, may be temporally/spatially organised in the
      startle brainstem centres. (2) Voluntary tibialis EMG activation was earlier and
      stronger in response to a startling stimulus (fall) than in response to a non
      startling stimulus (sound). This suggests that the startle response can be
      regarded as a reticular mechanism enhancing motor responsiveness. (3) Elderly
      subjects showed similar activation sequences but delayed by about 20 ms. This
      delay is more than can be accounted for by slowing of central and peripheral
      motor conduction, therefore suggesting age dependent delay in central processing.
      (4) Avestibular patients had normal latencies indicating that the free fall
      startle can be elicited by non-vestibular inputs. (5) Latencies in patients with
      idiopathic Parkinson's disease were normal whereas responses were earlier in
      patients with multiple system atrophy (MSA) and delayed or absent in patients
      with Steele-Richardson-Olszewski (SRO) syndrome. The findings in this patient
      group suggest: (1) lack of dopaminergic influence on the timing of the startle
      response, (2) concurrent cerebellar involvement in MSA may cause startle
      disinhibition, and (3) extensive reticular damage in SRO severely interferes with
      the response to free fall.

PMID- 10201416
TI  - Cervical spondylotic myelopathy in elderly people: a high incidence of conduction
      block at C3-4 or C4-5.
AB  - OBJECTIVES: To precisely localise the site of conduction block in elderly
      patients with cervical spondylotic myelopathy in the presence of multilevel
      compression shown by MRI. METHODS: A total of 44 patients aged 65 and older
      underwent serial intervertebral recording of spinal somatosensory evoked
      potentials (SSEPs) from either the intervertebral disc or the ligamentum flavum
      after epidural stimulation. The site of conduction block identified by abrupt
      reduction in size of the negative peak was designated as the 0 level with the
      other levels numbered in order of distance assigning a minus sign caudally.
      RESULTS: A single site of focal conduction block was disclosed in 42 patients, 23
      (55%) at C3-4, 17 (40%) at C4-5, and two (5%) at C5-6. At these levels (0), the
      amplitude of the negative component was reduced (p<0.0001) to 29% and the area to
      22%, with a concomitant increase (p<0.0001) of the initial positive component to
      150% in amplitude and 293% in area as compared to the-2 level which was taken as
      the baseline (100%). CONCLUSIONS: A high incidence (95%) of focal conduction
      block at C3-4 or C4-5 with normal conduction at C5-6 and C6-7 characterises
      cervical spondylotic myelopathy in elderly people. Incremental SSEP studies
      documenting the site of conduction block will help exclude clinically silent cord
      compression, directing the surgical intervention to the appropriate level of
      concern.

PMID- 10201417
TI  - Statistical power of MRI monitored trials in multiple sclerosis: new data and
      comparison with previous results.
AB  - OBJECTIVES: To evaluate the durations of the follow up and the reference
      population sizes needed to achieve optimal and stable statistical powers for two
      period cross over and parallel group design clinical trials in multiple
      sclerosis, when using the numbers of new enhancing lesions and the numbers of
      active scans as end point variables. METHODS: The statistical power was
      calculated by means of computer simulations performed using MRI data obtained
      from 65 untreated relapsing-remitting or secondary progressive patients who were
      scanned monthly for 9 months. The statistical power was calculated for follow up
      durations of 2, 3, 6, and 9 months and for sample sizes of 40-100 patients for
      parallel group and of 20-80 patients for two period cross over design studies.
      The stability of the estimated powers was evaluated by applying the same
      procedure on random subsets of the original data. RESULTS: When using the number
      of new enhancing lesions as the end point, the statistical power increased for
      all the simulated treatment effects with the duration of the follow up until 3
      months for the parallel group design and until 6 months for the two period cross
      over design. Using the number of active scans as the end point, the statistical
      power steadily increased until 6 months for the parallel group design and until 9
      months for the two period cross over design. The power estimates in the present
      sample and the comparisons of these results with those obtained by previous
      studies with smaller patient cohorts suggest that statistical power is
      significantly overestimated when the size of the reference data set decreases for
      parallel group design studies or the duration of the follow up decreases for two
      period cross over studies. CONCLUSIONS: These results should be used to determine
      the duration of the follow up and the sample size needed when planning MRI
      monitored clinical trials in multiple sclerosis.

PMID- 10201418
TI  - Significance of vomiting after head injury.
AB  - OBJECTIVES: To determine whether the presence and severity of post-traumatic
      vomiting can predict the risk of a skull vault fracture in adults and children.
      METHODS: Data were analysed relating to a consecutive series of 5416 patients
      including children who presented to an emergency service in the United Kingdom
      during a 1 year study period with a principal diagnosis of head injury.
      Characteristics studied were age, sex, speed of impact, level of consciousness on
      arrival, incidence of skull fracture, and the presence and severity of post
      traumatic vomiting. RESULTS: The overall incidence of post-traumatic vomiting was
      7% in adults and 12% in children. In patients with a skull fracture the incidence
      of post-traumatic vomiting was 28% in adults and 33% in children. Post-traumatic
      vomiting was associated with a fourfold increase in the relative risk for a skull
      fracture. Nausea alone did not increase the risk of a skull fracture and multiple
      episodes of vomiting were no more significant than a single episode. In patients
      who were fully alert at presentation, post-traumatic vomiting was associated with
      a twofold increase in relative risk for a skull fracture. CONCLUSION: These
      results support the incorporation of enquiry about vomiting into the guidelines
      for skull radiography. One episode of vomiting seems to be as significant as
      multiple episodes.

PMID- 10201419
TI  - Evaluating methods for estimating premorbid intellectual ability in closed head
      injury.
AB  - OBJECTIVES: The present study examines the utility of three measures of premorbid
      intellectual functioning in closed head injury, the National adult reading test
      (NART), the Cambridge contextual reading test (CCRT), and the spot the word test
      (STW). METHODS: In the first experiment, a group of 25 patients with closed head
      injury were compared with 50 healthy controls and 20 orthopaedic trauma controls.
      In the second experiment, the strength of correlation between the premorbid
      measures and current intellectual level were assessed in 114 healthy adults.
      RESULTS: The head injured group performed significantly more poorly than both
      control groups on measures of current intellectual ability. However, no
      significant differences emerged between the groups on any of the premorbid
      measures. In the large control sample, both the NART and the CCRT accounted for
      about 50% of the variance in current verbal intelligence. However, by contrast,
      the STW only accounted for 29% of the variability in verbal intelligence. Adding
      demographic variables to the prediction of current intellectual level increased
      the amount of variance explained to 60% for the NART, 62% for the CCRT, but only
      41% for the STW. CONCLUSION: The results provide supportive evidence for the use
      of the CCRT and NART in estimating premorbid intellectual functioning in patients
      who have sustained closed head injuries, but suggest caution when employing the
      STW.

PMID- 10201420
TI  - Measuring change in disability after inpatient rehabilitation: comparison of the
      responsiveness of the Barthel index and the Functional Independence Measure.
AB  - BACKGROUND: The importance of evaluating disability outcome measures is well
      recognised. The Functional Independence Measure (FIM) was developed to be a more
      comprehensive and "sensitive" measure of disability than the Barthel Index (BI).
      Although the FIM is widely used and has been shown to be reliable and valid,
      there is limited information about its responsiveness, particularly in comparison
      with the BI. This study compares the appropriateness and responsiveness of these
      two disability measures in patients with multiple sclerosis and stroke. METHODS:
      Patients with multiple sclerosis (n=201) and poststroke (n=82) patients
      undergoing inpatient neurorehabilitation were studied. Admission and discharge
      scores were generated for the BI and the three scales of the FIM (total, motor,
      and cognitive). Appropriateness of the measures to the study samples was
      determined by examining score distributions, floor and ceiling effects.
      Responsiveness was determined using an effect size calculation. RESULTS: The BI,
      FIM total, and FIM motor scales show good variability and have small floor and
      ceiling effects in the study samples. The FIM cognitive scale showed a notable
      ceiling effect in patients with multiple sclerosis. Comparable effect sizes were
      found for the BI, and two FIM scales (total and motor) in both patients with
      multiple sclerosis and stroke patients. CONCLUSION: All measures were appropriate
      to the study sample. The FIM cognitive scale, however, has limited usefulness as
      an outcome measure in progressive multiple sclerosis. The BI, FIM total, and FIM
      motor scales show similar responsiveness, suggesting that both the FIM total and
      FIM motor scales have no advantage over the BI in evaluating change.

PMID- 10201421
TI  - Relation between neuropsychological and neuroimaging findings in patients with
      late whiplash syndrome.
AB  - OBJECTIVES: The interpretation of long term cognitive impairment after whiplash
      injury is still a problem for many physicians. On the grounds of nuclear medicine
      findings previous research speculated that brain damage is responsible for
      cognitive problems of patients with whiplash. To test this hypothesis the
      relation between neuroimaging and neuropsychological findings was analysed.
      METHODS: Twenty one patients (11 women, 10 men, mean age 42.2 (SD 8.6) years)
      with the late whiplash syndrome (average interval of trauma 26.1 (SD 20.7)
      months) referred for diagnostic action to the Department of Neurology were
      investigated. Assessment included computer assisted assessment of working memory
      and divided attention, neuroimaging (by the means of [99mTc]-HMPAO-SPECT, [15O]
      H2O-PET and [18F]-FDG-PET), testing of emotional functioning (depression and
      anxiety ratings), and pain intensity at the time of testing. RESULTS: On average,
      scoring on tests of cognitive functioning was very low. However, no significant
      correlations were found between regional perfusion or metabolism in any brain
      area and the scores of divided attention or working memory. By contrast,
      significant relations were found between indices of impaired emotional
      functioning (state anxiety) and divided attention. In addition, low scoring in
      divided attention was significantly correlated with pain intensity at the time of
      testing. CONCLUSIONS: The present data do not provide evidence of a significant
      relation between detectable morphological or functional brain damage and impaired
      cognitive performance in the late whiplash syndrome. Results indicate triggering
      of emotional and cognitive symptoms on the basis of initial injury of the
      cervical spine.

PMID- 10201422
TI  - Prevention of poststroke depression: 1 year randomised placebo controlled double
      blind trial of mianserin with 6 month follow up after therapy.
AB  - OBJECTIVES: (1) To test whether early prophylactic antidepressive treatment by
      mianserin is able to prevent poststroke depression, and (2) to discover whether
      mianserin as an antidepressant has any beneficial influence on the outcome of
      ischaemic stroke. METHODS: A randomised, double blind, placebo controlled study
      involved 100 consecutive patients under 71 years old admitted to hospital for an
      acute ischaemic stroke; they were enrolled to receive 60 mg/day mianserin or
      placebo for 1 year. They were examined on admission, and at 2, 6, 12, and 18
      months with depression, stroke, and functional outcome scales. RESULTS: According
      to DSM-III-R, the prevalence of major depression was 6% at the initial stage, 11%
      at 1 year, and 16% at 18 months. At no time point did prevalences differ between
      the treatment groups, nor were differences found in depression scales, although
      at 2 months a greater improvement from initial assessment on the Hamilton
      depression scale was evident in patients on mianserin (p=0.05). Some beneficial
      changes on the Hamilton depression scale and Beck depression inventory were found
      in patients older than 56 (median age) and in men treated with mianserin, but not
      in other subgroups. Mianserin treatment did not affect stroke outcome as measured
      by neurological status, nor did it have any influence on functional outcome as
      measured by Rankin scale or Barthel index. CONCLUSION: It was not possible to
      show that early initiation of antidepressant therapy can prevent poststroke
      depression, because the prevalence of poststroke depression remained low even in
      patients on placebo. In this stroke population with a low rate of depressive
      patients, antidepressive medical treatment failed to affect stroke outcome.

PMID- 10201423
TI  - Isolated dysarthria due to extracerebellar lacunar stroke: a central monoparesis
      of the tongue.
AB  - OBJECTIVES: The pathophysiology of dysarthria can preferentially be studied in
      patients with the rare lacunar stroke syndrome of "isolated dysarthria". METHODS:
      A single study was carried out on seven consecutive patients with sudden onset of
      isolated dysarthria due to single ischaemic lesion. The localisation of the
      lesion was identified using MRI. The corticolingual, cortico-orofacial, and
      corticospinal tract functions were investigated using transcranial magnetic
      stimulation. Corticopontocerebellar tract function was assessed using 99mTc
      hexamethylpropylene amine oxime-single photon emission computerised tomography
      (HMPAO-SPECT) in six patients. Sensory functions were evaluated clinically and by
      somatosensory evoked potentials. RESULTS: Brain MRI showed the lesions to be
      located in the corona radiata (n=4) and the internal capsule (n=2). No
      morphological lesion was identified in one patient. Corticolingual tract function
      was impaired in all patients. In four patients with additional cortico-orofacial
      tract dysfunction, dysarthria did not differ from that in patients with isolated
      corticolingual tract dysfunction. Corticospinal tract functions were normal in
      all patients. HMPAO-SPECT showed no cerebellar diaschisis, suggesting unimpaired
      corticopontocerebellar tract function. Sensory functions were not affected.
      CONCLUSION: Interruption of the corticolingual pathways to the tongue is crucial
      in the pathogenesis of isolated dysarthria after extracerebellar lacunar stroke.

PMID- 10201425
TI  - Sarcoid tumour: continuing diagnostic problems in the MRI era.

PMID- 10201424
TI  - Impairment of willed actions and use of advance information for movement
      preparation in schizophrenia.
AB  - OBJECTIVES: To assess willed actions in patients with schizophrenia using
      reaction time (RT) tasks that differ in the degree to which they involve
      volitionally controlled versus stimulus driven responses. METHODS: Ten patients
      diagnosed with schizophrenia and 13 normal controls of comparable age were
      tested. Subjects performed a visual simple RT (SRT), an uncued four choice
      reaction time (CRT), and a fully cued four choice RT task. A stimulus 1(S1)
      stimulus 2(S2) paradigm was used. The warning signal/precue (S1) preceded the
      imperative stimulus (S2) by either 0 (no warning signal or precue) 200, 800,
      1600, or 3200 ms. RESULTS: The patients with schizophrenia had significantly
      slower RTs and movement times than normal subjects across all RT tasks. The
      unwarned SRT trials were significantly faster than the uncued CRT trials for both
      groups. For both groups, fully cued CRTs were significantly faster than the
      uncued CRTs. However, the S1-S2 interval had a differential effect on CRTs in the
      two groups. For the normal subjects fully cued CRTs and SRTs were equivalent when
      S1-S2 intervals were 800 ms or longer. A similar pattern of effects was not seen
      in the patients with schizophrenia, for whom the fully cued CRT were unexpectedly
      equivalent to SRT for the 200 ms interval and expectedly for the 1600 ms S1-S2
      interval, but not the 3200 or 800 ms intervals. CONCLUSIONS: Patients with
      schizophrenia were able to use advance information inherent in SRT or provided by
      the precue in fully cued CRT to speed up RT relative to uncued CRT. However, in
      the latter task, in which the volitional demands of preprogramming are higher
      since a different response has to be prepared on each trial, patients showed some
      unusual and inconsistent interval effects suggesting instability of attentional
      set. It is possible that future studies using RT tasks with higher volitional
      demands in patients with predominance of negative signs may disclose greater
      deficits in willed action in schizophrenia.

PMID- 10201426
TI  - Antiganglioside antibody in patients with Guillain-Barre syndrome who show bulbar
      palsy as an initial symptom.
AB  - OBJECTIVES: To identify valuable antiganglioside antibodies that support the
      diagnosis of Guillain-Barre syndrome (GBS) and its variants in patients showing
      bulbar palsy as an initial symptom. METHODS: Medical records of 602 patients with
      GBS or its variants were reviewed. Fifteen patients had bulbar palsy as an
      initial symptom. Serum antibodies against GM1, GM1b, GD1a, GalNAc-GD1a, GT1a, and
      GQ1b were examined in 13 of them. RESULTS: Serum antiganglioside antibodies were
      positive in 11 (85%) patients. IgG anti-GT1a (n=8; 62%) and anti-GM1b (n=7; 54%)
      antibodies were often present, whereas all the patients had low or no anti-GM1
      antibody activity. High anti-GD1a and anti-GQ1b IgG antibody titres were also
      present in some patients, but most had higher IgG antibody titres to GM1b or
      GT1a. All five patients with high IgG antibody titre to GM1b or GT1a only had had
      antecedent diarrhoea. Some patients with pharyngeal-cervical-brachial weakness
      (PCB) had IgG antibody to GT1a which did not cross react with GQ1b. Other
      patients with PCB had antibody to GT1a which cross reacted with GQ1b or antibody
      to GM1b, but anti-GM1b and anti-GT1a antibodies were not associated with the
      presence of bulbar palsy. All the patients who had no IgG antiganglioside
      antibodies recovered completely. CONCLUSIONS: Measurement of serum IgG anti-GT1a
      and anti-GM1b antibodies gives helpful support for the diagnosis of GBS and its
      variants when there is early involvement of the oropharyngeal function
      independently of other neurological findings which appear as the illness
      progresses.

PMID- 10201427
TI  - Unidirectional dyslexia in a polyglot.
AB  - Alexia is usually seen after ischaemic insults to the dominant parietal lobe. A
      patient is described with a particular alexia to reading Hebrew (right to left),
      whereas no alexia was noted when reading in English. This deficit evolved after a
      hypertensive right occipitoparietal intracerebral haemorrhage, and resolved
      gradually over the ensuing year as the haematoma was resorbed. The deficit
      suggests the existence of a separate, language associated, neuronal network
      within the right hemisphere important to different language reading modes.

PMID- 10201429
TI  - Memory guided saccade deficit after caudate nucleus lesion.
AB  - The role of the caudate nucleus in ocular motor control is not well determined in
      humans. Eye movements were recorded from a 45 year old man with infarctions
      involving bilaterally the body of the caudate nucleus, with a greater extent on
      the left side. The patient exhibited a pattern of eye movement abnormalities in
      which a delay dependent decrease of accuracy of memory guided saccades
      predominated. By contrast, memory guided pointing was normal. It is concluded
      that the body of the caudate nucleus participates in a spatial short term memory
      network devoted to eye movements.

PMID- 10201428
TI  - Proton magnetic resonance spectroscopy pattern of progressive multifocal
      leukoencephalopathy in AIDS.
AB  - The objective was to determine whether the use of intermediate echo times (135
      ms) in proton magnetic resonance spectroscopy (1H-MRS) detects a homogenous
      pattern in progressive multifocal leukoencephalopathy (PML) in HIV-1 infected
      people, and to confirm the results of previous studies. Six patients infected
      with HIV-1, with PML established by biopsy, and six healthy age and sex matched
      volunteers were evaluated to define their spectroscopic pattern. 1H-MRS spectra
      performed at 1.5 T were obtained with the STEAM sequence: TE/TM/TR, 20 ms/13.7
      ms/2000 ms; 2500 Hz, size 2048 points, 256 acquisitions (STEAM-20) and with the
      PRESS sequence; TE/TR, 135 ms/2000 ms; 2500 Hz, size 2048 points, 256
      acquisitions (PRESS-135). A single voxel was placed on the lesions and on the
      parieto-occipital white matter of controls. The peaks of N-acetylaspartate (NAA),
      choline (Cho), myoinositol (mI), lactate, and lipids were considered, and the
      results were expressed using creatine as reference. Spectra of PML lesions were
      characterised by significantly reduced NAA, lactate presence, and by
      significantly increased Cho and lipids compared with control group values. These
      results indicate that 1H-MRS detects a homogenous pattern in PML lesions. Recent
      studies, together with this, suggest that 1H-MRS may help in the diagnostic
      approach to patients with suspected PML lesions associated with AIDS.

PMID- 10201430
TI  - Ocular microtremor in patients with idiopathic Parkinson's disease.
AB  - Abnormalities in the oculomotor control mechanism of patients with idiopathic
      Parkinson's disease are well recognised. In this study the effect of Parkinson's
      disease on tonic output from oculomotor nuclei was studied by using
      oculomicrotremor as an index of such output. Oculomicrotremor readings were taken
      from 22 parkinsonian patients and 22 normal healthy volunteers using the
      piezoelectric strain gauge technique. There was a slower overall tremor
      frequency, baseline, and burst frequency in the parkinsonian group. There was
      also a significant increase in the duration of baseline, with a decrease in the
      number of bursts a second and a decrease in average duration of bursts in the
      patient group compared with the normal group. One patient, whose medication was
      withdrawn, showed a marked decrease in mean frequency and baseline frequency with
      a decrease in number of bursts and increase in baseline duration compared with
      readings taken when treatment recommenced. These results suggest that variables
      measured in oculomicrotremor are altered compared with normal subjects,
      reflecting altered tonic output from oculomotor nuclei in patients with
      idiopathic Parkinson's disease.

PMID- 10201431
TI  - Whipple's disease mimicking progressive supranuclear palsy: the diagnostic value
      of eye movement recording.
AB  - Treatable causes of parkinsonian syndromes are rare; Whipple's disease is one of
      them. A patient is described who presented with a parkinsonian syndrome and
      abnormal vertical gaze. Measurement of eye movements showed marked slowing of
      upward saccades, moderate slowing of downward saccades, a full range of voluntary
      vertical eye movements, curved trajectories of oblique saccades, and absence of
      square wave jerks. These features, atypical of progressive supranuclear palsy,
      suggested the diagnosis of Whipple's disease, which was subsequently confirmed by
      polymerase chain reaction analysis of intestinal biopsy material. Precise
      measurement of the dynamic properties of saccadic eye movements in parkinsonian
      patients may provide a means of identifying treatable disorders.

PMID- 10201432
TI  - Adam Politzer (1835-1920).

PMID- 10201433
TI  - Elementary visual hallucinations, blindness, and headache in idiopathic occipital
      epilepsy: differentiation from migraine.
AB  - This is a qualitative and chronological analysis of ictal and postictal symptoms,
      frequency of seizures, family history, response to treatment, and prognosis in
      nine patients with idiopathic occipital epilepsy and visual seizures. Ictal
      elementary visual hallucinations are stereotyped for each patient, usually
      lasting for seconds. They consist of mainly multiple, bright coloured, small
      circular spots, circles, or balls. Mostly, they appear in a temporal hemifield
      often moving contralaterally or in the centre where they may be flashing. They
      may multiply and increase in size in the course of the seizure and may progress
      to other non-visual occipital seizure symptoms and more rarely to extra-occipital
      manifestations and convulsions. Blindness occurs usually from the beginning and
      postictal headache, often indistinguishable from migraine, is common. It is
      concluded that elementary visual hallucinations in occipital seizures are
      entirely different from visual aura of migraine when individual elements of
      colour, shape, size, location, movement, speed of development, duration, and
      progress are synthesised together. Postictal headache does not show preference
      for those with a family history of migraine. Most of the patients are
      misdiagnosed as having migraine with aura, basilar migraine, acephalgic migraine,
      or migralepsy simply because physicians are not properly informed of differential
      diagnostic criteria. As a result, treatment may be delayed for years. Response to
      carbamazepine is excellent and seizures may remit.

PMID- 10201435
TI  - Harlequin syndrome.

PMID- 10201434
TI  - Affective symptoms in multiple system atrophy and Parkinson's disease: response
      to levodopa therapy.
AB  - The objective was to determine the extent to which psychiatric disturbances
      (especially mood disorders) generally considered poor prognostic factors, are
      present in patients with striatonigral (SND) type multiple system atrophy (MSA)
      compared with patients with idiopathic Parkinson's disease (IPD). The Hamilton
      depression scale (HAM-D), brief psychiatric rating scale (BPRS), and Unified
      Parkinson's disease rating scale (UPDRS) were administered to clinically probable
      non-demented patients with SND-type MSA and patients with IPD matched for age and
      motor disability, at baseline and after receiving levodopa. At baseline total HAM
      D score was greater in patients with IPD. Overall, BPRS score did not differ
      between the two groups; however, patients with IPD scored higher on anxiety items
      of the BPRS, and patients with MSA had higher scores on the item indicating
      blunted affect. After levodopa, both groups improved significantly in UPDRS and
      HAM-D total scores (just significant for patients with MSA). Patients with IPD
      improved significantly in total BPRS score but patients with MSA did not. At
      baseline patients with IPD were more depressed and anxious than patients with MSA
      who, by contrast, showed blunted affect. After levodopa, depression and anxiety
      of patients with IPD improved significantly whereas the affective detachment of
      patients with MSA did not change. Major neuronal loss in the caudate and ventral
      striatum, which are part of the lateral orbitofrontal and limbic circuits, may be
      responsible for the blunted affect not responsive to levodopa therapy found in
      patients with MSA.

PMID- 10201436
TI  - Disseminated cysticercosis.

PMID- 10201437
TI  - Prostatic carcinoma presenting as brain stem dysfunction.

PMID- 10201438
TI  - In vivo cerebral proton MRS in a case of subacute sclerosing panencephalitis.

PMID- 10201439
TI  - Alternating hemiplegia of childhood or Hashimoto's encephalopathy?

PMID- 10201440
TI  - Subthalamic nucleus stimulation improves directly levodopa induced dyskinesias in
      Parkinson's disease.

PMID- 10201441
TI  - Cerebral infarction: a rare complication of wasp sting.

PMID- 10201442
TI  - Cerebrospinal fluid manganese concentrations in patients with symmetric pallidal
      hyperintensities on T1 weighted MRI.

PMID- 10201443
TI  - The role of the nucleus intercalatus in vertical gaze holding.

PMID- 10201444
TI  - "Summary measure" statistic for assessing the outcome of treatment trials in
      relapsing-remitting multiple sclerosis.

PMID- 10201445
TI  - Hypothesis on the pathogenesis of vacuolar myelopathy, dementia, and peripheral
      neuropathy in AIDS.

PMID- 10201446
TI  - Does Helicobacter pylori affect the management of gastroesophageal reflux
      disease?

PMID- 10201447
TI  - It's not time to put away the biopsy forceps.

PMID- 10201448
TI  - Routine endoscopy in liver transplant candidates: is it indicated?

PMID- 10201449
TI  - Managing chronic pancreatitis pain: a block in time.

PMID- 10201450
TI  - Prevention and treatment of osteoporosis in patients with inflammatory bowel
      disease.
AB  - Osteopenia or osteoporosis is common in patients with inflammatory bowel disease.
      The use of corticosteroids contributes to the decline in bone loss; however,
      osteoporosis may develop in patients with inflammatory bowel disease independent
      of corticosteroid use. Risk factors for the development of low bone mass in
      patients with inflammatory bowel disease include the general risk factors for
      osteoporosis as well as additional factors such as the presence of chronic
      inflammation, use of corticosteroids and other pharmaceuticals, and nutritional
      deficiencies as the result of small bowel disease or small bowel resections.
      Despite the high prevalence, few patients are entered into prophylactic regimens
      to prevent corticosteroid-induced bone loss. The American College of Rheumatology
      has recently published recommendations for the prevention and treatment of
      corticosteroid-induced osteoporosis. In this article, we highlight the special
      risks for osteoporosis in patients with IBD and adapt the recommendations for
      prevention and treatment of osteoporosis to this clinical setting.

PMID- 10201451
TI  - Helicobacter pylori and the efficacy of omeprazole therapy for gastroesophageal
      reflux disease.
AB  - OBJECTIVE: Helicobacter pylori infection may affect gastric acid output and
      intragastric pH. In patients with an insufficient lower esophageal sphincter,
      this effect may theoretically influence the severity of reflux disease, as well
      as the efficacy of acid suppressive therapy. To evaluate whether the H. pylori
      status of patients with gastroesophageal reflux disease (GERD) affects the
      severity of disease and the efficacy of omeprazole therapy to maintain disease
      remission, we conducted this study. METHODS: Patients with GERD were
      prospectively studied by upper gastrointestinal endoscopy with biopsy sampling
      for histology and H. pylori culture before start of treatment and at annual
      follow-up. At endoscopy, esophagitis was graded according to the criteria of
      Savary-Miller, and the presence of Barrett's esophagus, hiatal herniation, or
      other abnormalities was recorded. Omeprazole was started at an initial dose of 20
      mg daily; the dose was adjusted based on symptoms and the endoscopical findings.
      RESULTS: One hundred thirty-seven GERD patients were included and followed up for
      a mean 56.6 months; 49 (36%) of them were infected with H. pylori. H. pylori
      infected and -uninfected patients did not differ with respect to age (60 +/- 13
      vs 61 +/- 14 yr, p = 0.65) or duration of follow-up (54 +/- 30 vs 58 +/- 31
      months, p = 0.12). H. pylori-negative patients tended to present with more severe
      esophagitis at baseline (median Savary-Miller score 3 vs 2, p = 0.06) and had a
      higher prevalence of Barrett's esophagus (39/88 vs 10/49, p = 0.006). However, no
      difference was found with respect to the dose of omeprazole needed for maintained
      relief of symptoms and endoscopical signs of esophagitis (median 40 mg in both
      groups, p = 0.35). CONCLUSIONS: H. pylori-negative GERD patients have a higher
      prevalence of Barrett's esophagus, but do not need a higher dose of omeprazole to
      maintain symptomatic and endoscopical disease remission.

PMID- 10201452
TI  - Sensitivity of antiendomysium and antigliadin antibodies in untreated celiac
      disease: disappointing in clinical practice.
AB  - OBJECTIVE: We have undertaken a study to assess the efficiency of serological
      tests in the diagnosis of celiac disease (CD) during the period January 1, 1994
      to January 7, 1997. Our aim was to evaluate the sensitivity of IgA antiendomysium
      (EMA) and IgA antigliadin (AGA) with regard to the degree of histological
      abnormality in biopsy specimens of small intestine in untreated celiac disease
      patients and first-degree relatives. METHODS: The study population comprised 101
      cases: 85 untreated celiac patients and 16 first-degree relatives with a mean age
      of 42 yr (range, 2-76 yrs). Sixteen of 85 were excluded from study because they
      did not satisfy the study or diagnostic criteria of CD. EMA and AGA have been
      compared with the degree of villous atrophy (VA) in 69 celiac patients and 16
      relatives according to the Marsh criteria of 1992. We divided the Marsh III
      histology into three subgroups as follows: Marsh IIIa (partial VA), Marsh IIIb
      (subtotal VA), and Marsh IIIc (total villous atrophy). RESULTS: The specificity
      and positive predictive value of EMA for CD was excellent, because all EMA
      positive patients (n = 42) were diagnosed with CD. The sensitivity of EMA,
      however, differed between CD subgroups; in patients with total VA, the
      sensitivity of EMA was 100% (17/17). However, in patients with partial VA (Marsh
      IIIa), the sensitivity of EMA was disappointing, only 9/29 (31%). Three of 72
      celiacs with Marsh IIIb and Marsh IIIc had IgA deficiency and were excluded from
      the study. Elevated AGA has been detected in the sera of 39 of 69 (62%) patients.
      A combination of EMA and AGA tests showed a sensitivity of 76% (53/69). None of
      16 first-degree relatives with Marsh I-II had positive EMA. CONCLUSIONS:
      Interpretation of negative serology needs great awareness. Although EMA
      sensitivity in total villous atrophy is excellent, in partial villous atrophy the
      sensitivity of EMA appears to be disappointing. Our experience shows that EMA and
      AGA have only limited value in screening programs for CD.

PMID- 10201453
TI  - Prevalence of upper and lower gastrointestinal tract findings in liver transplant
      candidates undergoing screening endoscopic evaluation.
AB  - OBJECTIVE: The incidence of esophageal and gastric varices and portal
      hypertensive gastropathy (PHG) has been well studied in cirrhotic patients.
      Because little is known of the prevalence of other upper and lower
      gastrointestinal tract pathology in pre-liver transplant candidates, we
      retrospectively studied the prevalence of and factors associated with these
      findings. METHODS: One hundred and twenty pre-liver transplant candidates
      underwent esophagogastroduodenoscopy to evaluate for varices, and 71 of them also
      underwent flexible sigmoidoscopy to screen for colorectal carcinoma. The
      association of upper and lower GI tract pathology with Child-Pugh Class, etiology
      of cirrhosis, and signs of portal hypertension, including presence and size of
      esophageal varices, presence of gastric varices, PHG, ascites, and splenomegaly,
      was analyzed using univariate and multivariate analysis. RESULTS: Etiology of
      cirrhosis among 87 men and 33 women (mean age, 52 yr) included 25% hepatitis C,
      27% hepatitis C/alcohol, 15% alcohol, 10% primary sclerosing cholangitis/primary
      biliary cirrhosis, 9% cryptogenic, 8% metabolic, and 6% hepatitis B. Prevalence
      of Child-Pugh Classes A, B, and C were 34%, 49%, and 17%, respectively; 73% of
      patients had esophageal varices (23% were large), 62% PHG (23% were severe), and
      16% gastric varices. Excluding varices and PHG, endoscopic findings in the upper
      GI tract (n = 120) included: 13% esophagitis/ulcers, 7.5% gastritis, 8%
      duodenitis, 2% Barrett's esophagus, 3% duodenal ulcers, and 2% gastric ulcers.
      Findings in the lower gastrointestinal tract (n = 71) included 21% adenomatous
      polyps, 21% internal hemorrhoids, 15% diverticulosis, 7% rectal varices, 3%
      colopathy, and 3% vascular ectasias. Univariate analysis revealed that there was
      a significant association between rectal varices and severe PHG (p < 0.05). This
      association was not maintained when multivariate analysis was performed.
      CONCLUSIONS: Among all the findings, only rectal varices and colopathy were of
      higher prevalence in the pre-liver transplant population than that reported for
      the general population. No significant associations were found between these
      gastrointestinal tract lesions and patient characteristics.

PMID- 10201454
TI  - A prospective randomized comparison of endoscopic ultrasound- and computed
      tomography-guided celiac plexus block for managing chronic pancreatitis pain.
AB  - OBJECTIVE: Computed tomography (CT)-guided celiac plexus neurolysis has been used
      for controlling the chronic abdominal pain associated with intra-abdominal
      malignancy and chronic pancreatitis. Endoscopic ultrasound (EUS)-guided celiac
      plexus neurolysis has been reported to have some success in controlling pain from
      pancreatic cancer. The aim of this study is to assess the efficacy of EUS-guided
      celiac plexus block versus CT-guided celiac plexus block for controlling the
      chronic abdominal pain associated with chronic pancreatitis. METHODS: Patients
      enrolled were randomly assigned to EUS-guided or CT-guided celiac plexus block.
      Pain scores were determined pre- and postceliac block for both techniques. Follow
      up was obtained by a nurse at 1 day post-block, then weekly thereafter for 24 wk.
      Patients also rated overall experience with these procedures. The EUS celiac
      block was performed with a 22-gauge sterile needle inserted into the celiac
      region with guidance of real-time linear array endosonography followed by
      injection of 10 ml of bupivacaine (0.75%) and 3 ml (40 mg) of triamcinolone on
      both sides of the celiac area. RESULTS: Twenty-two consecutive patients (10 men,
      12 women), were ultimately enrolled in this study between 7/1/95 and 12/30/95;
      four patients were excluded for protocol violations. We performed EUS-guided
      celiac block in 10 patients and CT-guided celiac block in eight. A significant
      improvement in pain scores with reduction in pain medication usage occurred in
      50% (five of 10) of patients having the EUS block. The mean postprocedure follow
      up was 15 weeks (range: 8-24 wk). Persistent benefit was experienced by 40% of
      patients at 8 wk and by 30% at 24 wk. In the patients with CT block, however,
      only 25% (two of eight) had relief. The mean follow-up was 4 wk (range: 2-6 wk).
      Only 12% (one of eight) had some relief at 12 wk of follow-up. There were no
      complications. EUS-guided celiac block was the preferred technique among patients
      who experienced both techniques. A cost comparison between both celiac block
      techniques shows EUS to be less costly than CT. CONCLUSIONS: EUS-guided celiac
      block provided more persistent pain relief than CT-guided block and was the
      preferred technique among the subjects studied. EUS-guided celiac block appears
      to be a safe, effective, and less costly method for controlling the abdominal
      pain that can accompany chronic pancreatitis in some patients.

PMID- 10201455
TI  - Endoscopic ultrasound cannot determine suitability for esophagectomy after
      aggressive chemoradiotherapy for esophageal cancer.
AB  - OBJECTIVE: Endoscopic ultrasound (EUS) provides important information in the
      initial staging of patients with esophageal cancer. With recent modifications in
      chemoradiotherapy protocols, a significant number of patients have no residual
      tumor at esophagectomy. The high surgical morbidity and mortality might be
      avoided if complete response to chemoradiotherapy could be predicted. Previously
      published clinical trials, with relatively small patient numbers, have suggested
      that EUS may accurately stage esophageal cancer after chemoradiotherapy. The aim
      of this study was to verify the accuracy of EUS in staging esophageal cancer
      after effective chemoradiotherapy. METHODS: EUS staging was performed before and
      after concurrent cisplatin, 5-fluorouracil, and hyperfractionated radiotherapy in
      59 patients with newly diagnosed esophageal cancer. All patients underwent
      subsequent esophagectomy and pathological staging. The accuracy of preoperative,
      postchemoradiotherapy EUS was evaluated in a retrospective fashion by comparison
      to pathological staging. RESULTS: After chemoradiotherapy, 18 patients (31%) had
      no residual disease at pathological staging (T0N0). However, EUS correctly
      predicted complete response to chemoradiotherapy (T0N0) in only three patients
      (17%). The accuracy of postchemoradiotherapy EUS for pathological T stage was
      only 37%, and its sensitivity for N1 disease was only 38%. EUS was unable to
      distinguish postradiation fibrosis and inflammation from residual tumor.
      CONCLUSION: When aggressive preoperative chemoradiotherapy is provided to
      patients with esophageal cancer, the predictive value of postchemoradiotherapy
      EUS is inadequate for use in clinical decision making.

PMID- 10201456
TI  - Specialized columnar epithelium of the esophagogastric junction: prevalence and
      associations. The Central Finland Endoscopy Study Group.
AB  - OBJECTIVES: In Barrett's esophagus (BE) normal squamous esophageal epithelium is
      replaced by specialized columnar epithelium (SCE). BE is related to
      gastroesophageal reflux disease (GERD) and is a risk factor for esophageal
      adenocarcinoma. SCE is detected also at normal-appearing esophagogastric junction
      without BE (junctional SCE). The relationships between junctional SCE, GERD, and
      cardia adenocarcinoma are obscure and controversial. The aims of the present
      study were to investigate the prevalence and demographics of junctional SCE and
      to compare these figures with those reported for BE, and esophageal and cardia
      adenocarcinoma. A further aim was to examine the association between junctional
      SCE and GERD, Helicobacter pylori infection, and gastritis. METHODS: One thousand
      one hundred-nineteen consecutive dyspeptic patients underwent gastroscopy and
      were enrolled into the study. RESULTS: Junctional SCE was detected in 110
      patients (10%). The age-specific prevalence of junctional SCE increased with age.
      The male:female ratio was 1:1.1. In multivariate analysis, junctional SCE was
      independently and positively related to endoscopic erosive esophagitis (odds
      ratio [OR], 1.8; 95% confidence interval [CI], 1.1-3.1), cardia inflammation
      (carditis) (OR, 3.1; 95% CI, 1.4-6.8), and age (OR, 1.4 per decade; 95% CI, 1.2
      1.6), but not to corpus H. pylori infection (OR, 1.4; 95% CI, 0.7-2.8), antral
      (OR, 1.0; 95% CI, 0.5-2.1) or corpus (OR, 0.8; 95% CI, 0.4-1.8) gastritis, or
      intestinal metaplasia of the antral mucosa in stomach (OR, 1.2; 95% CI, 0.7-2.1).
      In univariate analysis, junctional SCE was, however, significantly more common in
      patients with antral-predominant atrophic gastritis (20%), compared with those
      with normal gastric histology (8%, p < 0.001). CONCLUSIONS: Junctional SCE is age
      related and may therefore be an acquired lesion. It is associated with cardia
      inflammation and endoscopic erosive esophagitis, but not with H. pylori infection
      or gastric intestinal metaplasia. Unlike BE and cardia cancer, junctional SCE
      occurs with similar frequency in men and women.

PMID- 10201457
TI  - Gastroesophageal reflux in diabetes mellitus.
AB  - OBJECTIVE: Although abnormal gastroesophageal (GE) reflux is the most frequent
      alteration of the gastrointestinal tract, its prevalence in diabetes mellitus
      (DM) is not widely known. The objective of this study was to analyze both the
      presence of abnormal GE reflux in diabetic patients with no esophageal symptoms
      and the influence of cardiovascular autonomic neuropathy (CVAN) in the
      development of abnormal GE reflux. METHODS: Fifty insulin-dependent diabetic
      patients, averaging 29.2 +/- 9.0 yr of age, who had had diabetes for > 5 yr and
      showed no symptoms or history of gastroesophageal disease, were compared with a
      control group composed of 36 healthy volunteers (18 men, 18 women) whose average
      age was 35.9 +/- 10.1 yr. The cardiovascular autonomic nervous system was
      examined in the diabetics and control subjects who complied with inclusion
      criteria. Long-term (24-h) ambulatory esophageal pH monitoring was performed, as
      well as a manometric study of the lower esophageal sphincter. RESULTS: The
      parameters obtained from the monitoring showed significant differences (p < 0.01)
      between DM and control subjects. Abnormal GE reflux, defined as any percentage of
      time with esophageal pH < 4 exceeding 3.5% of total time (8.7 +/- 5.6%; range,
      4.1-24.4%), was detected in 14 patients. Diabetic subjects were classified
      according to cardiovascular autonomic neuropathy tests (without CVAN [n = 19,
      38%] and with abnormal CVAN tests [n = 31, 62%]). The pH monitoring parameters
      showed significant differences between these two groups (p < 0.05). CONCLUSIONS:
      A higher prevalence (28%) of abnormal GE reflux appeared among asymptomatic
      diabetic patients than among the general population. The presence of abnormal GE
      reflux in diabetic patients was associated with the existence of cardiovascular
      autonomic neuropathy (abnormal GE reflux = 38.7% in diabetic patients with
      abnormal CVAN tests vs 10.5% in diabetic patients without CVAN).

PMID- 10201458
TI  - Different effects of an oral anticholinergic drug on gastroesophageal reflux in
      upright and supine position in normal, ambulant subjects: a pilot study.
AB  - OBJECTIVE: There is controversy in the literature on the effects of
      anticholinergic drugs on gastroesophageal reflux. Our aim was to study more
      extensively the effects of an oral anticholinergic drug on esophageal motility
      and gastroesophageal reflux in normal ambulant subjects under different
      circumstances: upright, supine, fed, and fasted state. METHODS: Fifteen healthy
      subjects (seven men, eight women), mean age 34 yr (range, 22-61 yr) underwent
      randomized placebo-controlled 16-h evening and overnight ambulatory esophageal
      motility/pH study. After a 3-day loading dose of either oral dicyclomine (Dic) 20
      mg four times daily or placebo (Pla), an ambulatory esophageal motility/pH study
      was performed while taking medication or placebo. Each study was analyzed for
      meal, first and second h postprandial, upright and supine periods, and first 2 h
      supine after bedtime snack. RESULTS: The mean number of reflux episodes decreased
      with dicyclomine during the first h postprandial (Dic, 1.9 vs Pla, 2.5; p <
      0.05). During the first 2 h supine, mean number of reflux episodes increased with
      dicyclomine (Dic, 1.4 vs Pla, 0.8; p < 0.09), as did mean percent time pH < 4
      (Dic, 2.6 vs Pla, 0.5; p < 0.04), with an increase in clearance time (Dic, 0.9 vs
      Pla, 0.3; p < 0.05; in min). Mean peristaltic amplitude decreased with
      dicyclomine during the 2nd h postprandial (Dic, 48.8 vs Pla, 56.3; p < 0.04).
      CONCLUSIONS: Oral dicyclomine caused a decrease in early postprandial upright
      reflux episodes, but also significantly increased the percent time pH < 4 during
      the first two h supine. Therefore, its effects are dependent on body position and
      fasted or fed state. Our results justify additional studies with oral
      anticholinergic agents in patients with gastroesophageal reflux disease.

PMID- 10201459
TI  - Omeprazole versus high-dose ranitidine in mild gastroesophageal reflux disease:
      short- and long-term treatment. The Dutch Reflux Study Group.
AB  - OBJECTIVE: Patients with reflux esophagitis suffer from a chronic condition that
      may cause considerable discomfort because of recurrent symptoms and diminished
      quality of life. This study was designed to evaluate acute and long-term
      treatment comparing standard doses of omeprazole and high-dose ranitidine.
      METHODS: Patients with endoscopically verified symptomatic esophagitis grade I or
      II were initially treated with omeprazole 20 mg daily or ranitidine 300 mg twice
      daily for 4-8 wk. Patients who were symptom free were randomized to maintenance
      treatment with omeprazole 10 mg daily or ranitidine 150 mg twice daily. Patients
      were seen every 3 months or at symptomatic relapse. RESULTS: The percentage of
      asymptomatic patients after 4 and 8 wk treatment were 61% and 74%, respectively,
      for omeprazole and 31% and 50%, respectively, for ranitidine. Of 446 patients
      treated initially, 277 were asymptomatic, of whom 263 entered the maintenance
      study. The estimated proportion of patients in remission after 12 months of
      maintenance treatment with omeprazole 10 mg daily (n = 134) and ranitidine 150 mg
      twice daily (n = 129) were 68% and 39%, respectively (p < 0.0001). CONCLUSIONS:
      Omeprazole 20 mg daily is superior to high-dose ranitidine in the symptomatic
      treatment of reflux esophagitis grade I and II. Furthermore, omeprazole at half
      the standard dose is more effective than ranitidine in a standard dose in keeping
      patients in remission for a period of 12 months.

PMID- 10201461
TI  - Clinicopathological features of superficial depressed-type colorectal neoplastic
      lesions.
AB  - OBJECTIVE: We performed this study to analyze the endoscopic findings, dissecting
      microscopic features, and p53 immunostaining in superficial depressed-type
      (depressed) colorectal neoplastic lesions. METHODS: Dissecting stereomicroscopy
      was used to ascertain the size and pit pattern of lesions removed by endoscopic
      snare polypectomy. Immunohistochemical staining of p53 was performed with an
      antigen retrieval system using a monoclonal antibody to p53. RESULTS: All
      depressed neoplastic lesions (submucosal carcinoma, n = 6; high-grade dysplasia,
      n = 14; and adenoma, n = 30) were small (< 1 cm in diameter) and were detected as
      a depression with or without a marginal elevation on colonoscopic examination. In
      the dissecting microscopic study, submucosal carcinomas and lesions of high-grade
      dysplasia almost exclusively showed irregular small pits, with the exception of
      four malignant lesions with moderate submucosal invasion in which the pit
      structure was absent. In contrast, adenomas had either regular small (29/30
      lesions) or oval pits (1/30 lesions). Rates of p53 positivity were 100%, 64%, and
      7% in depressed submucosal carcinomas, lesions of high-grade dysplasia, and
      adenomas, respectively, thus the prevalence of p53 positivity was significantly
      higher in the former two groups than in the adenoma group. CONCLUSIONS: The high
      frequency of invasive carcinoma and high-grade dysplasia found in depressed
      colorectal neoplastic tumors, despite their small size, indicates that these
      lesions may be a subtype of colorectal tumor with more aggressive malignant
      potential at an earlier stage.

PMID- 10201460
TI  - Does this patient have Barrett's esophagus? The utility of predicting Barrett's
      esophagus at the index endoscopy.
AB  - OBJECTIVES: Few studies have evaluated the ability of the endoscopist to predict
      the presence of Barrett's esophagus (BE) at index endoscopy. The goals of this
      study were to determine the operating characteristics of endoscopy in diagnosing
      BE, and to determine the clinical and endoscopic predictors of BE in suspected BE
      patients at the index endoscopy. METHODS: From September 1993 to October 1997,
      endoscopic reports were examined to identify patients with suspected BE. All
      esophageal pathology reports during the same period were evaluated for the
      presence of specialized intestinal metaplasia. RESULTS: During the study period,
      4053 endoscopies were performed on 2393 patients. Eight percent of all procedures
      were performed for suspected or confirmed BE. Fifty-three patients were known to
      have BE and thus their reports were excluded from this analysis. Five hundred
      seventy of the remaining patients had esophageal biopsies performed, and were
      included in this analysis. Among these 570 patients, 146 were suspected to have
      BE on endoscopy, while 424 were not suspected to have BE at the time of
      endoscopy. There were no differences among the two groups in terms of gender,
      race, and dyspepsia as an indication for the endoscopy. However, suspected BE
      patients were slightly younger and were more likely to have heartburn, but were
      less likely to have dysphagia as an indication for the endoscopy. The sensitivity
      and specificity of the endoscopists' assessments were 82% (95% confidence
      interval [CI], 72-92) and 81% (95% CI, 78-84), respectively. The positive
      predictive value and the negative predictive value were 34% and 97%,
      respectively. The positive likelihood ratio was 4.32 (95% CI, 3.49-5.31) and the
      negative likelihood ratio was 0.22 (95% CI, 0.13-0.38). Univariate analysis
      showed that endoscopists diagnosed BE in those with long-segment BE (LSBE) more
      accurately than in those with short-segment BE (SSBE) (55% vs 25% p = 0.001; odds
      ratio [OR] = 3.63, 95% CI, 1.71-7.70). Barrett's esophagus was correctly
      diagnosed in 38.5% of white patients but in only 14.7% of black patients (p =
      0.01; OR = 3.63, 95% CI, 1.31-10.13). Multivariable logistic regression
      identified only the length of the columnar-appearing segment (p = 0.002; OR =
      3.33, 95% CI, 1.54-7.17) and race (p = 0.08; OR = 2.31, 95% CI, 0.88-6.03) to be
      associated with the presence of BE on biopsy. CONCLUSIONS: Barrett's esophagus is
      frequently suspected at endoscopy; SSBE was more frequently suspected than LSBE,
      but was correctly diagnosed only 25% of the time, versus 55% for LSBE.
      Endoscopists diagnosed BE with a sensitivity of 82% and a specificity of 81%.
      However, the positive predictive value was only 34%, whereas the negative
      predictive value was 97%. The length of the columnar-appearing segment is the
      strongest predictor of BE at endoscopy. Alternative methods are needed to better
      identify BE patients endoscopically, especially those with SSBE.

PMID- 10201462
TI  - The effect of antibiotic therapy on bleeding from duodenal ulcer.
AB  - OBJECTIVE: We conducted this study to test whether eradication of Helicobacter
      pylori (H. pylori) infection prevents hemorrhage related to duodenal ulcer.
      METHODS: Patients with H. pylori infection and endoscopically proven duodenal
      ulcers without ulcer-related hemorrhage were enrolled into four randomized,
      double-blind, multicenter studies using the same study protocol. They were
      treated with clarithromycin plus omeprazole (441 patients), omeprazole alone (447
      patients), or ranitidine alone (263 patients). Success of H. pylori eradication
      was evaluated by the 13C-urea breath test 4-6 wk after the last dose of study
      drug. Follow-up continued at monthly intervals up to 1 yr after the last dose of
      study drug. RESULTS: Bleeding due to duodenal ulcer was not observed in any
      patients who received clarithromycin plus omeprazole, whereas five patients in
      the omeprazole treatment group and six patients in the ranitidine treatment group
      experienced an episode of ulcer-related hemorrhage during follow-up. All patients
      who experienced ulcer-related bleeding were male. When compared by bleeding,
      there were no significant differences with respect to ethnicity, alcohol
      consumption, or tobacco use. H. pylori infection was no longer detectable in 68%
      of patients after treatment with clarithromycin plus omeprazole, compared with 5%
      after treatment with omeprazole alone or 4% after treatment with ranitidine
      alone. CONCLUSION: In a population of duodenal ulcer patients without
      predisposing risk factors for ulcer bleeding, antibiotic eradication or
      suppression of H. pylori infection prevented the occurrence of ulcer-related
      hemorrhage for up to 1 yr after therapy.

PMID- 10201463
TI  - Effectiveness of ranitidine bismuth citrate, clarithromycin, and metronidazole
      therapy for treating Helicobacter pylori.
AB  - OBJECTIVE: There are limited data available from the United States on the
      effectiveness of ranitidine bismuth citrate (RBC) plus two antibiotics to treat
      Helicobacter pylori. Therefore, the following study was undertaken to evaluate
      RBC with two antibiotics, which have been used successfully in combination, to
      treat H. pylori. METHODS: Adults with and without abdominal symptoms, who had
      never received H. pylori eradication therapy, were tested for the presence of H.
      pylori infection either by in-office rapid serology assays or histology. Positive
      subjects were administered the 13C-urea breath test. Subjects who had a positive
      urea breath test were then treated with RBC 400 mg b.i.d., clarithromycin 500 mg
      b.i.d., and metronidazole 500 mg b.i.d. for 10 days. Four to 6 wk after
      completing antibiotics all subjects were asked to return for a second urea breath
      test to assess treatment success. RESULTS: Forty-seven of the 50 subjects
      enrolled into this study completed the antibiotic regimen and returned for a
      repeat urea breath test. Thirty-seven subjects were negative for H. pylori by
      urea breath test and 10 were positive, resulting in a 79% eradication rate. Seven
      subjects (14%) stopped their medication because of side effects. When analysis
      was performed on the 40 subjects who took > or = 80% of their medication (per
      protocol), the eradication rate was 90%. CONCLUSIONS: The combination of RBC with
      clarithromycin and metronidazole successfully treated H. pylori infection after
      only 10 days of therapy. The per-protocol eradication rate from this study was
      similar to that seen with Food and Drug Administration (FDA)-approved regimens.
      In conclusion, RBC plus clarithromycin and metronidazole should be considered as
      a first-line treatment regimen for H. pylori infection, and may only need to be
      taken for a period of 10 days, as opposed to 14 days for FDA-approved regimens.

PMID- 10201464
TI  - Comparison of [13C]urea blood test to [13C]urea breath test for the diagnosis of
      Helicobacter pylori.
AB  - OBJECTIVE: It has been determined that the [13C]urea breath test (UBT) is a safe
      and effective way of detecting Helicobacter pylori (H. pylori) infection. Some
      individuals may have difficulty performing the exhalation component of the test,
      possibly due to age, or mental or physical compromise. Our aim was to determine
      if a commercially developed [13C]urea blood test could be utilized as a
      substitute for the UBT to detect H. pylori infection. METHODS: Patients who were
      referred by their physicians for UBT were offered study inclusion. Patients
      underwent baseline and 30-min UBT. A simultaneous blood sample of 3 cc was drawn
      into a heparinized vacutainer at the 30-min period of the UBT. [13C]urea levels
      in both blood and breath samples were analyzed using isotope ratio mass
      spectrometry. UBT > or = 6 delta per mil over baseline and urea blood tests > (
      17 delta per mil) were considered positive. RESULTS: One hundred sixty-one
      patients (68 men/93 women) with average age of 47.0 +/- 14.2 yr were tested.
      Agreement between breath and blood test results occurred in 153/161 (95%) cases.
      Using the UBT as the diagnostic standard, the urea blood test resulted in 44 true
      positive, 109 true negative, four false positive, and four false negative
      results, giving a sensitivity of 92%, specificity of 96%, positive predictive
      value of 92%, and negative predictive value of 96%. CONCLUSIONS: The urea blood
      test was found to be comparable to the urea breath test in the detection of H.
      pylori infection. The urea blood test will be accurate in the diagnosis of active
      H. pylori infection.

PMID- 10201465
TI  - Once-daily therapy for H. pylori infection: a randomized comparison of four
      regimens.
AB  - OBJECTIVE: We sought to determine the efficacy and tolerability of novel, once
      daily therapies in the treatment of Helicobacter pylori infection. METHODS: One
      hundred sixty subjects with H. pylori infection documented by endoscopic biopsy
      or serology plus 13C-urea breath test were randomly assigned to omeprazole 80 mg
      q.d. and metronidazole extended-release formulation 750 mg q.d. for 10 days (OM);
      OM plus amoxicillin 1.5 g q.d. for 10 days (OMAm); OM plus azithromycin 500 mg
      q.d. for 7 days (OMAz); or OM plus clarithromycin 1 g q.d. for 10 days (OMCI). A
      repeat breath test was done 6 wk after the completion of therapy. Subjects were
      considered compliant if they took > or = 80% of each study medication as
      prescribed. RESULTS: Intent-to-treat eradication rates were OM = 8% (95%
      confidence interval [CI], 2-20%), OMAm = 35% (95% CI, 21-52%), OMAz = 65% (95%
      CI, 48-79%), and OMCI = 78% (95% CI, 62-89%). Lack of compliance was seen in 5%
      of subjects given OM, 8% given OMAm, 3% given OMAz, and 15% given OMCI.
      CONCLUSIONS: This pilot study demonstrated that once-daily triple therapy with
      high-dose omeprazole, metronidazole extended-release formulation, and
      clarithromycin achieved an eradication rate approaching 80%. Further study may
      permit development of optimal once-daily dosing and enhance eradication rates.

PMID- 10201466
TI  - Patient recall and appropriate timing for obtaining informed consent for
      endoscopic procedures.
AB  - OBJECTIVES: Although informed consent is an issue in many medical malpractice
      claims, there is no standardized time or method to obtain informed consent for
      endoscopic procedures. The objectives of this study were to determine whether
      sedation for endoscopic procedures interfered with pre-endoscopic informed
      consent and to determine the appropriate time to obtain informed consent.
      METHODS: Patients undergoing a sedated esophagogastroduodenoscopy had informed
      consent obtained either 48-72 h before the procedure (group 1A, n = 50) or 10-60
      min before the procedure (group 1B, n = 50). Patients undergoing an unsedated
      flexible sigmoidoscopy had informed consent obtained either 48-72 h before (group
      2A, n = 47) or 10-60 min before the procedure (group 2B, n = 49). Methods of
      informed consent consisted of an oral and a written explanation about the
      procedure. Patients were sedated with midazolam and meperidine. A Trieger test
      evaluated recovery from sedation. Recall was assessed by asking six questions
      about the procedure before discharge and again 2-3 days later. RESULTS: Standard
      t tests and Mann-Whitney U nonparametric rank tests were used to compare the 1) 1
      h recall scores, 2) 2-3-day recall scores, and 3) recall difference scores for
      groups 1A and 1B, 1A and 2A, 2A and 2B, and 1B and 2B. There were no differences
      in recall for the different groups. CONCLUSIONS: This study shows that sedation
      for endoscopic procedures does not interfere with pre-endoscopic informed
      consent. Informed consent for endoscopic procedures can be obtained at any time
      before sedation with similar recall.

PMID- 10201467
TI  - Sump syndrome: endoscopic treatment and late recurrence.
AB  - OBJECTIVE: Biliary sump syndrome is a rare complication of biliary-enteric
      anastomosis. Classically, the distal bile duct becomes obstructed by food,
      stones, or debris after choledochoenterostomy. Endoscopic sphincterotomy has been
      recommended as the primary and definitive treatment modality. The aim of our
      study was to confirm the short and long term therapeutic efficacy of endoscopic
      treatment in a long follow-up period. METHODS: The series include 31 patients
      with characteristic clinical illness after choledochoduodenostomy. All of them
      were successfully treated by endoscopic sphincterotomy and bile duct clearance
      with a balloon catheter or basket. The follow-up period ranged from 18 to 84
      months (median: 51 months). RESULTS: Clinical improvement was immediate in all
      patients. No complications were recorded. Recurrence of the syndrome, with
      restenosis of the sphincterotomy opening, was observed in six patients (19%) and
      was treated successfully and safely with a new papillotomy. Sump syndrome
      recurrence occurred 31-72 months (median: 58.5 months) after the initial
      treatment. CONCLUSIONS: We report a considerably high recurrence rate of sump
      syndrome after initially successful endoscopic management and its effective
      endoscopic treatment with a new papillotomy. We still believe that the primary
      therapeutic approach in patients with sump syndrome should be endoscopic.

PMID- 10201468
TI  - Elevated plasma levels of glucagon-like peptide-1 after oral glucose ingestion in
      patients with pancreatic diabetes.
AB  - OBJECTIVE: The purpose of the present study was to evaluate plasma glucagon-like
      peptide-1 (GLP-1) responses after oral glucose ingestion in patients with chronic
      pancreatitis and to clarify how GLP-1 secretion relates to pancreatic diabetes.
      METHODS: An oral glucose tolerance test (OGTT) was performed in 17 patients with
      chronic pancreatitis. Plasma glucose, immunoreactive insulin (IRI), C-peptide,
      glucagon, and GLP-1 levels at each time point during OGTT were measured. The
      diagnosis of chronic pancreatitis was made by the findings of endoscopic
      retrograde pancreatography (ERP): evident dilation of the main pancreatic duct
      with or without pancreatolithiasis. RESULTS: The patients were divided into three
      groups according to the World Health Organization classification of diabetes
      based on plasma glucose levels after OGTT. The groups were: normal (three
      patients), impaired glucose tolerant (IGT) (six patients), and diabetic (DM)
      (eight patients). In the DM group, IRI and C-peptide response levels after oral
      glucose ingestion were significantly reduced as compared with those of the normal
      and IGT groups. No significant glucagon responses to oral glucose ingestion were
      found in the three groups. In contrast, plasma GLP-1 levels were significantly
      elevated after oral glucose ingestion in the DM groups as compared with normal
      and IGT groups. CONCLUSIONS: The present study affords evidence that plasma GLP-1
      levels become elevated with development of pancreatic diabetes, although the
      precise mechanism of this elevation remains undetermined.

PMID- 10201469
TI  - Use of corticosteriods in the prevention of post-ERCP pancreatitis: results of a
      controlled prospective study.
AB  - OBJECTIVE: The aim of this prospective controlled study was to determine whether
      prophylactic corticosteroids decrease the incidence of post-ERCP pancreatitis.
      METHODS: A double-blind comparison of hydrocortisone (100 mg by i.v. infusion
      immediately before endoscopy) with placebo (sodium chloride administered in the
      same fashion). A total of 535 patients (286 women and 249 men, with an average
      age of 58.6 yr) who were scheduled to undergo diagnostic or operative ERCP
      underwent randomization. Six patients were excluded from the final evaluation for
      various reasons. The remaining 529 patients, 263 in the hydrocortisone group and
      266 in the placebo group, were analyzed. Patients were divided into subgroups
      with regard to high risk factors for acute pancreatitis after ERCP. RESULTS: The
      overall incidence of acute pancreatitis was 5.3% (28 of 529 patients). Procedure
      induced pancreatitis occurred in 15 of 263 (5.7%) patients treated with
      hydrocortisone and in 13 of 266 (4.9%) patients treated with placebo (p = NS).
      The results of analysis of risk factors for pancreatitis did not evidence any
      significant difference between the hydrocortisone group and the placebo group.
      CONCLUSIONS: Hydrocortisone does not prevent acute pancreatitis after diagnostic
      or therapeutic ERCP.

PMID- 10201470
TI  - Autonomic nervous system tone measured by baroreflex sensitivity is depressed in
      patients with end-stage liver disease.
AB  - OBJECTIVES: Chronic liver disease is often associated with impairment of
      autonomic nervous system (ANS) reflexes. Baroreflex sensitivity (BRS) testing is
      an inexpensive, relatively noninvasive test that can be used to assess ANS tone.
      The aims of the present study were to determine the prevalence of ANS dysfunction
      in cirrhotics who are being considered for liver transplantation and to explore
      the potential use of BRS as a prognostic tool in identifying patients awaiting
      transplantation who are at increased risk for death. METHODS: We studied nine
      cirrhotics who were awaiting liver transplantation and seven controls without
      liver disease. BRS (ms/mm Hg) was measured using the phenylephrine method.
      RESULTS: BRS (mean +/- SEM) (ms/mm Hg) was significantly lower in cirrhotics
      compared with controls (4.2 +/- 0.9 vs 21.1 +/- 3.8 ms/mm Hg; p < 0.05).
      Furthermore, BRS was lower in cirrhotics with hepatic encephalopathy compared
      with those without (2.6 +/- 0.9 vs 6.1 +/- 1.0 ms/mm Hg; p < 0.05) and there was
      a trend toward lower BRS values in Child-Pugh class C patients as compared with
      class B (3.8 +/- 1.3 vs 5.3 +/- 1.2 ms/mm Hg; p = 0.3). At follow-up (9 months),
      one patient had died and one underwent liver transplantation. These two patients
      also had the most severely impaired vagal tone (BRS = 0 and 1.2 ms/mm Hg,
      respectively). CONCLUSIONS: Vagal tone, as assessed by BRS, is markedly depressed
      in cirrhotic patients awaiting liver transplantation.

PMID- 10201471
TI  - A pilot study of rimantadine for patients with chronic hepatitis C unresponsive
      to interferon therapy.
AB  - OBJECTIVE: Therapeutic options are limited for chronic hepatitis C patients who
      have not responded to a course of interferon therapy. Recently, a 6-month course
      of amantadine was shown to result in a sustained virological response in chronic
      hepatitis C patients who were unresponsive to interferon therapy. The aim of this
      study was to evaluate the effect of rimantadine on chronic hepatitis C patients
      who had not responded to interferon therapy. METHODS: This was an open label
      trial involving 17 patients who were treated with rimantadine 100 mg b.i.d. for 6
      months. Changes in serum aminotransferase activities and HCV-RNA levels were
      determined. RESULTS: Mean alanine aminotransferase activities and HCV RNA levels
      did not change significantly during therapy. HCV RNA remained detectable in all
      patients throughout therapy. Neurologic symptoms (headaches, nervousness, and
      dizziness) developed in 29% of patients. A total of 12% of patients required dose
      reduction after 12 wk of therapy because of dizziness. CONCLUSION: Rimantadine
      has no significant antiviral activity against HCV.

PMID- 10201472
TI  - Ascites and liver test abnormalities during severe ovarian hyperstimulation
      syndrome.
AB  - OBJECTIVE: Severe ovarian hyperstimulation syndrome is an uncommon cause of
      ascites that is being increasingly recognized because of the high number of women
      undergoing assisted reproductive techniques, mainly in vitro fertilization. This
      prospective study investigates the clinical and biochemical characteristics of a
      large series of patients with this syndrome and ascites, including renal and
      electrolyte abnormalities, activity of neurohormonal systems participating in the
      regulation of extracellular fluid volume, and liver function tests. METHODS: This
      was a prospective longitudinal study including 50 consecutive patients with
      ascites due to severe ovarian hyperstimulation syndrome. Renal function, serum
      electrolytes, body weight, mean arterial pressure, pulse rate, plasma renin
      activity, plasma concentration of aldosterone, norepinephrine, antidiuretic
      hormone and atrial natriuretic peptide, and standard liver function tests were
      measured during the syndrome and 4-5 wk after recovery. A sample of ascitic fluid
      was obtained from eight patients for protein measurement and cell count. RESULTS:
      At diagnosis, patients had ascites associated with low urinary sodium excretion,
      oliguria, and hyponatremia. They had also markedly low arterial pressure and
      increased pulse rate in association with marked activation of vasoconstrictor and
      antinatriuretic factors. The ascitic fluid was characterized by a high protein
      concentration, low leukocyte count, and relatively high number of red blood
      cells. Fifteen (30%) patients had abnormal liver tests characterized by mild to
      moderate increases in AST (mean 103 +/- 17.1 IU/L) and ALT (76 +/- 8.3 IU/L),
      which were associated in some cases with increases in gamma-glutamyl
      transpeptidase or alkaline phosphatase. All abnormalities reverted to normal
      after the resolution of the syndrome. CONCLUSIONS: With the increasing use of
      assisted reproductive techniques, physicians should be aware of severe ovarian
      hyperstimulation syndrome as a cause of ascites. The syndrome is associated with
      sodium retention, hyponatremia, arterial hypotension, and marked activation of
      vasoconstrictor and antinatriuretic systems. In one third of patients, liver
      tests abnormalities are present.

PMID- 10201474
TI  - Clinical significance of portal lymphoid aggregates/follicles in Chinese patients
      with chronic hepatitis C.
AB  - OBJECTIVE: Portal lymphoid aggregates/follicles (lymphoid A/F) is a
      characteristically histological finding in patients with chronic hepatitis C. We
      assessed the prevalence of lymphoid A/F in Chinese patients with chronic
      hepatitis C and evaluated the correlation of this phenomenon with clinical,
      biochemical, immunological, virological, and other histological features of these
      patients. METHODS: Eighty-nine Chinese patients with chronic hepatitis C were
      enrolled and portal lymphoid A/F was evaluated in liver biopsy. Clinical,
      biochemical, immunological, histological, and virological data, including serum
      HCV RNA titer and HCV genotype and the response to interferon therapy, were
      compared between patients with and without portal lymphoid A/F. RESULTS: Twenty
      nine (33%) of 89 patients with chronic hepatitis C had portal lymphoid A/F.
      Patients with lymphoid A/F had a significantly higher frequency of HCV genotype
      1b infection (p = 0.039) and had a significantly higher mean score of bile duct
      damage, periportal necroinflammation, and portal inflammation in liver
      histologies when compared with patients without lymphoid A/F. No significant
      difference in sex distribution, mean age, history of blood transfusion, serum
      liver biochemistry, presence of serum autoantibodies/cryoglobulinemia, serum
      viral titer, and response to interferon therapy was noted between the two groups.
      Multivariate logistic regression analysis showed HCV genotype 1b infection and
      periportal necroinflammation were significant independent predictors associated
      with portal lymphoid A/F. CONCLUSIONS: The presence of portal lymphoid A/F in
      Chinese patients with chronic hepatitis C was significantly correlated with HCV
      genotype 1b infection and periportal necroinflammation.

PMID- 10201473
TI  - The clinical significance of simultaneous infection with hepatitis G virus in
      patients with chronic hepatitis C.
AB  - OBJECTIVES: Hepatitis G virus (HGV) is a recently discovered member of the
      flavivirus family that has been associated with acute and chronic hepatitis. HGV
      infection has been reported to coexist in 10-20% of patients with chronic
      hepatitis C. The significance of simultaneous infection with HGV and hepatitis C
      virus (HCV) remains to be clarified, as do the effects on HGV of therapeutic
      interventions such as interferon treatment or liver transplantation. THE AIMS OF
      OUR STUDY WERE: 1) to examine the frequency of HGV infection in the settings of
      liver transplantation and interferon therapy for hepatitis C; and 2) to compare
      HGV RNA levels before and after liver transplantation or interferon treatment.
      METHODS: Pre-treatment sera were available in 65 patients with chronic hepatitis
      C treated with interferon; pretransplant sera were available in 49 patients
      transplanted for end stage liver disease associated with chronic hepatitis C.
      Information collected included age, sex, risk factors for hepatitis, concurrent
      liver disease, patient and allograft survival, biochemical response to
      interferon, histological activity index, and degree of fibrosis/cirrhosis. HCV
      genotyping was performed by sequencing the NS-5 region. HGV quantitation was
      performed using a research-based branched DNA (bDNA) assay with a set of probes
      directed at the 5' untranslated region. RESULTS: HGV was detected in 10 of 49
      patients (20%) before transplant and in 13 of 65 patients (20%) treated with
      interferon. There was a female predominance among HGV-positive compared with HGV
      negative transplant patients (80% vs 20%; p < 0.01), but such a difference was
      not observed in the interferon-treated group. Hepatic iron concentration was
      lower in hepatic explants from patients who were HGV-positive than in those who
      were HGV-negative (318 +/- 145 microg/g dry weight vs 1497 +/- 2202 microg/g dry
      weight; p = 0.02). HCV exposure after 1980 was more common in the HGV-positive
      patients than in those who were HGV-negative for the entire study population (10
      of 20 [50%] vs 16 of 66 [24%]; p = 0.03), as well as for the nontransplant
      subgroup (8 of 12 [67%] vs 12 of 39 [31%]; p = 0.03). HGV RNA levels declined at
      1 yr after transplant in seven of eight patients. Among nine patients tested
      during or after interferon treatment, HGV RNA levels declined from pretreatment
      levels in all and disappeared in three. CONCLUSIONS: Among patients with chronic
      hepatitis C treated with either interferon or liver transplantation, the
      frequency of coinfection with HGV is about 20%. HGV may be a more recent virus in
      the US than HCV. Coinfection with HGV does not appear to affect the likelihood of
      response to interferon in patients with hepatitis C. Finally, HGV RNA levels
      appear to decline after both liver transplantation and interferon therapy,
      suggesting possible suppression by increased HCV replication in the former case,
      and a possible drug treatment effect in the latter.

PMID- 10201475
TI  - Effects of octreotide on central hemodynamics and systemic oxygen use in patients
      with viral cirrhosis.
AB  - OBJECTIVE: Octreotide has potentially beneficial effects in patients with
      cirrhosis. However, the effects of octreotide on central hemodynamics and oxygen
      use have not been established. The present study was undertaken to evaluate the
      effect of octreotide on central hemodynamics and oxygen use in patients with
      viral cirrhosis. METHODS: Twenty-five patients with cirrhosis were enrolled in
      the study. They were randomly assigned to receive either placebo (n = 10) or a
      continuous infusion of 100 microg/h of octreotide after an initial 100-microg
      bolus (n = 15). Hemodynamic measurements and oxygenation values were obtained
      before and 60 min after octreotide or placebo administration. RESULTS: Placebo
      administration did not have any effect on hemodynamic and oxygenation values. In
      patients who received octreotide, systemic hemodynamic values including cardiac
      index, mean arterial pressure, and systemic vascular resistance were not
      affected. The mean pulmonary arterial pressure tended to increase after
      octreotide administration but was statistically insignificant. There was a
      significant increase in pulmonary arterial vascular resistance, whereas the
      pulmonary capillary wedge pressure and right atrial pressure were significantly
      decreased. Arterial oxygen tension, systemic oxygen uptake, and oxygen extraction
      ratio were significantly decreased after octreotide administration, whereas
      oxygen transport as well as arterial and mixed venous oxygen contents remained
      unchanged. CONCLUSIONS: In patients with viral cirrhosis, octreotide
      administration exerted a significant effect on pulmonary circulation. It also
      resulted in a decrease in systemic oxygen uptake and oxygen extraction ratio.
      These results suggested that octreotide may impair tissue oxygenation in patients
      with viral cirrhosis.

PMID- 10201476
TI  - The ratio of aspartate aminotransferase to alanine aminotransferase: potential
      value in differentiating nonalcoholic steatohepatitis from alcoholic liver
      disease.
AB  - OBJECTIVE: The ratio of aspartate aminotransferase (AST) to alanine
      aminotransferase (ALT) is often greater than 2:1 in alcoholic hepatitis. The
      purpose of this study was to determine whether this ratio may be used to
      distinguish nonalcoholic steatohepatitis (NASH) from alcoholic liver disease.
      METHODS: Patients with NASH were matched with controls with alcoholic liver
      disease based on age, gender, and date of diagnosis. The diagnosis of alcoholic
      liver disease was based on exclusion of other causes and a significant history of
      alcohol consumption. The diagnosis of nonalcoholic steatohepatitis was based on
      exclusion of other causes of liver disease and a liver biopsy showing > 10%
      steatosis and inflammation. The two sided Student t test was used for statistical
      analysis. RESULTS: From 1990 to 1996, 70 patients with NASH were matched with 70
      subjects with alcoholic liver disease. Patients with NASH had a mean AST to ALT
      ratio of 0.9 (range 0.3-2.8, median 0.7) and subjects with alcoholic liver
      disease a mean ratio of 2.6 (range 1.1-11.2, median 2.0). The mean AST levels
      were 66 U/L and 152 U/L, and the mean ALT levels 91 U/L and 70 U/L, in the
      nonalcoholic steatohepatitis and alcoholic liver disease groups, respectively.
      Although the absolute aminotransferase levels were significantly different in the
      two groups (p < 0.05), the greatest difference was observed in the AST to ALT
      ratio (p < 0.000001). Subset analysis of patients with NASH revealed mean AST to
      ALT ratios of 0.7, 0.9, and 1.4 for subjects with no fibrosis, mild fibrosis, or
      cirrhosis, respectively. The differences among these ratios were statistically
      significant (p < 0.05). CONCLUSIONS: The AST to ALT ratio appears to be a useful
      index for distinguishing nonalcoholic steatohepatitis from alcoholic liver
      disease. Although values < 1 suggest NASH, a ratio of > or = 2 is strongly
      suggestive of alcoholic liver disease.

PMID- 10201477
TI  - Abnormalities of the electrogastrogram in functional gastrointestinal disorders.
AB  - OBJECTIVE: Cutaneous electrogastrography records gastric electrical activity and
      detects gastric arrhythmias. Abnormalities of the electrogastrogram have been
      described in a variety of disorders, but their specificity and their prevalence
      in patients with functional gastrointestinal disorders has not been reported. The
      aim of this study was to assess the specificity of electrogastrography as well as
      the prevalence and pattern of abnormalities in functional dyspepsia and irritable
      bowel syndrome. METHODS: Electrogastrography was performed in 170 patients with
      functional dyspepsia, 70 patients with irritable bowel syndrome, 20 patients with
      gastroesophageal reflux disease, and 30 asymptomatic controls. The abnormal
      electrogastrogram was defined as <70% normal electrical activity either before or
      after a test meal. RESULTS: The electrogastrogram was abnormal in 36% of patients
      with functional dyspepsia and in 25% with irritable bowel syndrome who complained
      of concurrent dyspepsia. The electrogastrogram was normal in 93% of asymptomatic
      controls, 90% of patients with gastroesophageal reflux, and 92% of patients with
      irritable bowel syndrome who did not complain of dyspepsia. As a group,
      functional dyspepsia patients had a greater degree of tachygastrias both before
      (p < 0.02) and after (p < 0.01) a test meal. The electrical frequency after the
      test meal was also more unstable (p < 0.003). CONCLUSIONS: The electrogastrogram
      is abnormal in approximately 36% of functional dyspepsia patients and has a
      specificity of approximately 93%. Electrogastrography defines a subgroup of
      patients with functional dyspepsia and electrical rhythm disturbance. In
      irritable bowel syndrome, the electrogastrogram is usually abnormal only if
      concurrent dyspepsia is present.

PMID- 10201478
TI  - Pain: the overlooked symptom in gastroparesis.
AB  - OBJECTIVE: Abdominal pain has not been reported generally as a significant
      feature of the clinical presentation of patients with gastroparesis. METHODS:
      Using a standardized questionnaire, we analyzed the clinical features of 28
      consecutive patients referred with established or suspected gastroparesis over a
      4-yr period. The diagnosis of gastroparesis was supported by abnormalities in
      gastric emptying studies (GES), electrogastrography (EGG), or upper endoscopy
      (EGD). Diagnostic tests were reviewed. RESULTS: A total of 12 male (mean age 39.5
      yr) and 18 female patients (mean age 39.6 yr) were included in this study. These
      patients had been symptomatic for an average of 37.8 months before their referral
      to our center. Seven of these patients had insulin-dependent diabetes. Idiopathic
      gastroparesis was present in more than half of the patients. The symptom profile
      of the 28 patients was as follows: nausea, 92.9%; abdominal pain, 89.3%; early
      satiety, 85.7%; and vomiting, 67.9%. The pain was described as burning, vague, or
      crampy in nature. Only 36% localized to the upper abdomen. In all, 60% of
      patients complained of postprandial pain, whereas 80% complained of nocturnal
      pain that interfered with their normal sleeping pattern. In general, pain
      responded poorly or not at all to prokinetic agents. CONCLUSIONS: Nausea and
      abdominal pain are the most common complaints of patients with gastroparesis. In
      80% of patients, GES and EGG correlated positively.

PMID- 10201479
TI  - Compliance curves during peritoneal dialysate infusion are like a distensible
      tube and are similar at multiple UGI sites.
AB  - OBJECTIVE: Disorders from increased intraabdominal pressure (IAP) result from
      filling the abdominal cavity beyond its capacity. The aims of this study were 1)
      to examine pressure:volume curves as fluid is infused into the intraabdominal
      cavity, and 2) to ascertain the best UGI site for indirect IAP measurements.
      METHODS: Chronic ambulatory peritoneal dialysis patients were studied (n = 4)
      supine. On day 1, manometry catheters measured IAP indirectly (intragastric and
      intrarectal) and intraesophageal (three sites) pressure. On day 2, antral
      duodenal-jejunal manometry was performed to compare indirectly measured IAP at
      multiple sites. On both days, dialysate was infused at 200 ml/min until IAP was >
      or = 15 mm Hg or patient experienced severe discomfort. RESULTS: Filling had
      three phases: 1) an initial small increase in IAP as infusion began; 2) minimal
      further increase in IAP during infusion to about 3 L concurrent with a
      progressive increase in abdominal girth and mild abdominal discomfort; and 3) a
      linear increase in IAP with infusion > 3 L concurrent with intense abdominal
      discomfort and little increase in abdominal girth. During study day 2,
      intragastric, intraduodenal, and intrajejunal pressures were usually similar.
      CONCLUSIONS: The compliance curve of the abdomen with filling is similar to that
      of the bladder and large veins. Compliance curves with provocative meals may be
      useful in evaluating postprandial abdominal pain, dyspepsia, and bloating.

PMID- 10201480
TI  - Celiac disease and markers of celiac disease latency in patients with primary
      Sjogren's syndrome.
AB  - OBJECTIVE: Many autoimmune diseases occur concomitantly with celiac disease. We
      investigated prospectively the occurrence of celiac disease and small-bowel
      mucosal inflammation in patients with primary Sjogren's syndrome. METHODS: A
      total of 34 patients with primary Sjogren's syndrome and 28 controls underwent
      small bowel biopsy. Villous morphology, jejunal intraepithelial lymphocytes, and
      mucosal HLA-DR were evaluated and DQA and DQB alleles, serum antiendomysial, and
      antigliadin antibodies were examined. RESULTS: Five (14.7%) of 34 Sjogren's
      syndrome patients were found to have celiac disease. The density of jejunal
      intraepithelial gammadelta+ T cells was increased in all celiac and in four
      nonceliac patients. All celiac patients, 69% of nonceliac Sjogren's syndrome
      patients, and 11% of control subjects showed enhanced HLA-DR expression (p <
      0.001). HLA DQ2 was present in 19 (56%) patients with Sjogren's syndrome,
      including all five with celiac disease. CONCLUSIONS: The findings show a close
      association between Sjogren's syndrome and celiac disease. Even among nonceliac
      patients with primary Sjogren's syndrome, an ongoing inflammation is often
      present in the small bowel mucosa.

PMID- 10201481
TI  - Increased risk of cancer in ulcerative colitis: a population-based cohort study.
AB  - OBJECTIVE: There is an increased risk of colorectal cancer among patients with
      ulcerative colitis (UC). However, the overall and site specific cancer risks in
      these patients have been investigated to a limited extent. To study the
      association between UC and cancer, a population-based study of 1547 patients with
      UC in Stockholm diagnosed between 1955 and 1984 was carried out. METHODS: The
      patients were followed in both the National Cancer Register and the National
      Cause of Death Register until 1989. For comparisons, regional cancer incidence
      rates in Stockholm County were used together with individually computed person
      years at risk in the UC disease cohort. RESULTS: A total of 121 malignancies
      occurred among 97 individuals as compared with 89.8 expected (standardized
      morbidity ratio [SMR] = 1.4; 95% confidence interval (CI), 1.1-1.6). Overall, an
      excess number of colorectal cancers (SMR, 4.1; 95% CI, 2.7-5.8), and
      hepatobiliary cancers in men (SMR = 6.0; 95% CI, 2.8-11.1) associated with
      primary sclerosing cholangitis, was observed. The risk of pulmonary cancer was
      decreased (SMR = 0.3; 95% CI, 0.1-0.9). In all, 91 extracolonic malignancies were
      observed, compared with the 82.3 expected (SMR = 1.11; 95% CI, 0.9-1.3).
      CONCLUSIONS: In UC patients, the overall cancer incidence is increased mainly
      because of an increased incidence of colorectal and hepatobiliary cancer. This
      increase is partly counterbalanced by a decreased risk of pulmonary cancer
      compared with that in the general population.

PMID- 10201482
TI  - Cytomegalovirus infection in patients with inflammatory bowel disease.
AB  - OBJECTIVE: It has been suggested that, in inflammatory bowel disease,
      cytomegalovirus behaves in the intestine as a nonpathogenic bystander, and even
      its finding in intestinal mucosa has unclear clinical relevance. We report our
      experience with a small series of patients with refractory inflammatory bowel
      disease and cytomegalovirus infection and their clinical outcome. METHODS AND
      RESULTS: Nine patients with moderate-severe attacks of inflammatory bowel disease
      did not respond to i.v. prednisone (1 mg/kg/day) for a mean of 24 days. Four of
      these patients were further treated with i.v. cyclosporine A (4 mg/kg/day).
      Cytomegalovirus infection was diagnosed in two patients after resection for
      treatment failure. In the remaining patients, cytomegalovirus infection was
      diagnosed in endoscopic mucosal biopsies and i.v. ganciclovir was then
      administered at a dose of 10 mg/kg/day for 2-3 wk. Five of these patients went
      into clinical remission, allowing corticosteroid and cyclosporine A
      discontinuation. Follow-up biopsies were performed and in all cases
      cytomegalovirus could not be detected in the colonic tissue. Two patients needed
      to be treated with intravenous cyclosporine A after antiviral therapy because of
      persistence of clinical symptoms despite the elimination of cytomegalovirus
      infection. CONCLUSIONS: Cytomegalovirus infection may play a role in the natural
      history of refractory inflammatory bowel disease and in some of its
      complications. The clearance of cytomegalovirus in colonic mucosa may lead some
      of these patients to remission.

PMID- 10201483
TI  - In vitro production of endomysial antibodies in cultured duodenal mucosa from
      patients with celiac disease.
AB  - OBJECTIVE: Endomysial antibodies (EMAs) had been found recently after in vitro
      gluten challenge of duodenal mucosa from treated celiac patients. This was a
      promising result for diagnosis of potential/latent celiac disease. Therefore, we
      tested the usefulness of the production of EMAs of in vitro-challenged mucosa for
      diagnosis of celiac disease and determined the location of EMA production.
      METHODS: We investigated EMAs in the serum, in the supernatants of in vitro
      gliadin-challenged duodenal mucosa specimens in 68 patients, and in homogenized
      native duodenal and gastric specimens in seven patients. Twenty-one of the 68
      patients served as nonceliac controls, 11 as candidates for potential celiac
      disease, 23 celiac patients were on glutenfree diet, and 13 were newly diagnosed.
      RESULTS: EMAs were just found in the supernatants of duodenal biopsies of those
      celiac patients who had demonstrable EMAs in serum, independent of gliadin
      challenge. In these patients EMAs were also found in homogenized native duodenal
      biopsies, but not in gastric biopsies. CONCLUSIONS: EMAs seem to be produced in
      the small bowel mucosa of celiac patients, but not in other tissues such as
      gastric mucosa. The production of EMAs could not be initiated under standard in
      vitro conditions and therefore, such as in vitro challenge cannot be used for
      diagnostic purposes.

PMID- 10201484
TI  - Elevated pancreatic enzymes in inflammatory bowel disease are associated with
      extensive disease.
AB  - OBJECTIVE: Our aim was to perform a cross-sectional study to estimate the
      prevalence of elevated pancreatic enzymes in patients with inflammatory bowel
      disease and to correlate the enzyme activities with clinical, endoscopic, and
      histological findings. METHODS: Two hundred thirty-seven patients diagnosed with
      inflammatory bowel disease (IBD), including a subgroup with known hepatobiliary
      disease, were studied crosssectionally. Serum and urinary pancreatic enzymes were
      prospectively sampled and compared to endoscopic and histological findings
      obtained previously. RESULTS: Hyperamylasemia was found in 11% and hyperlipasemia
      in 7% of the total study group. The corresponding prevalences in patients with
      Crohn's disease were 17% and 9%, those in ulcerative colitis 9% and 7%, and those
      in indeterminate colitis 10% and 5%, respectively. High levels of serum amylase
      and pancreatic isoamylase were associated with extensive colonic disease (p <
      0.005) and high histological activity (p < 0.05). Amylase, but not lipase, was
      significantly elevated in patients with primary sclerosing cholangitis. Smokers
      showed higher urinary amylase levels than non- and ex-smokers. The use of
      medication had no influence on the enzyme levels. CONCLUSIONS: Pancreatic enzymes
      are elevated in a significant proportion of patients with IBD, and the enzyme
      increase is associated with a more extensive and active disease, and in some
      cases with primary sclerosing cholangitis.

PMID- 10201486
TI  - The effect of octreotide on gastroduodenal blood flow measured by laser Doppler
      flowmetry in rabbits and man.
AB  - OBJECTIVE: The somatostatin analogue, octreotide is valuable in the management of
      variceal bleeding, and it has been suggested that it may stop peptic ulcer
      hemorrhage by reducing gastroduodenal blood flow or increasing intragastric pH.
      The aim of this study was to determine the effect of intravenous octreotide
      infusion on gastroduodenal mucosal blood flow and gastric pH. METHODS: Seven New
      Zealand white rabbits and five healthy human volunteers were used. Mucosal blood
      flow was measured using a laser Doppler flowmeter (LDF). The Doppler probe was
      positioned in the upper gastrointestinal tract of the seven rabbits and five
      human volunteers. Blood flow was measured before and after octreotide infusion.
      RESULTS: In the animal experiments, mucosal blood flow was decreased in a dose
      dependent manner in the gastric body (209.1-56.3 U) (p < 0.008), antrum (143.3
      33.3 U) (p < 0.02) and duodenum (254-67.6 U) (p < 0.016) by doses of octreotide
      ranging from 10-50 microg/kg of body weight. In the human studies, mucosal blood
      flow was decreased in the gastric body (p < 0.016) and antrum (p < 0.009) after
      octreotide infusion (dose 1-1.5 microg/kg). Intragastric pH was significantly
      increased (p < 0.05). The change was not associated with systemic hemodynamic
      changes. CONCLUSIONS: Gastroduodenal mucosal blood flow was reduced and
      intragastric pH increased by octreotide. This agent could be helpful in the
      management of gastroduodenal mucosal bleeding.

PMID- 10201485
TI  - Increased expression of angiogenic factors in human colonic angiodysplasia.
AB  - OBJECTIVE: Angiodysplasia of the colon is a distinct vascular abnormality
      characterized by focal accumulation of ectatic vessels in the mucosa and
      submucosa. To investigate whether angiogenesis contributes to the pathogenesis of
      human colonic angiodysplasia, we examined the expression of basic fibroblast
      growth factor (bFGF) and vascular endothelial growth factor (VEGF), and its
      endothelial cell receptors flt-1 and KDR. METHODS: Immunohistochemistry was
      performed in sections of specimens obtained from 18 patients with colonic
      angiodysplasia and from eight patients with colon cancer and its adjacent,
      histologically normal margins of resection. We used affinity-purified rabbit
      polyclonal antibodies and a streptoavidin-biotin peroxidase method. RESULTS: We
      detected strong immunoreactivity for vascular endothelial growth factor,
      homogeneously distributed in the endothelial lining of blood vessels of all sizes
      in 16 (89%) specimens of colonic angiodysplasia and in seven (88%) patients with
      colon cancer. In contrast, very limited immunoreactivity was found in normal
      colon. Vascular staining for flt-1 was observed in eight (44%) and one (12.5%) of
      the colonic angiodysplasia or colon cancer specimens, respectively, but not in
      normal colon. Vascular immunoreactivity for basic fibroblast growth factor was
      observed in seven (39%) specimens from patients with colonic angiodysplasia,
      whereas either very limited or no immunostaining was found in sections from
      specimens of patients with colon cancer and its normal margins. CONCLUSIONS: In
      human colonic angiodysplasia, increased expression of angiogenic factors is
      likely to play a pathogenic role.

PMID- 10201487
TI  - Magnetic resonance iron-free nodules in genetic hemochromatosis.
AB  - OBJECTIVE: In hemochromatosis, areas of normal hepatic magnetic resonance (MR)
      signal intensity indicate the presence of iron-free-nodules, which are strongly
      suspected of being neoplastic. The goal of the study was to define the prevalence
      and the nature of these iron-free MR nodules at the time of diagnosis in 116
      patients included in a prospective study assessing the accuracy of MR imaging
      (MRI) in the quantification of liver iron overload. METHODS: Seventy-nine of the
      116 patients had homozygous hemochromatosis on a phenotypic basis. Fifteen
      millimeter-thick contiguous slices were performed using T1- and T2-weighted
      gradient echo sequences with a 0.5 Tesla magnet. RESULTS: Six of 79 homozygous
      hemochromatotic patients had one or more MR iron-free nodules. Five of the six
      patients proved to have malignant tumors. Four of six iron-free nodules were
      hepatocellular carcinoma (5% in the hemochromatosis group and 17.5% in
      hemochromatotic patients with severe fibrosis). CONCLUSIONS: The present data
      confirm the high prevalence of liver cancer at the time of diagnosis, mainly in
      cirrhotic patients greater than 45 years of age, and indicate that, when
      performing MRI for liver iron quantification, a complete hepatic MRI examination
      is preferable to a simple signal measurement in patients at risk for
      hepatocellular carcinoma.

PMID- 10201488
TI  - Endoscopic band ligation of Dieulafoy's lesion: report of two cases and review of
      the literature.
AB  - Two cases of endoscopic band ligation as lone therapy for Dieulafoy's lesions are
      presented. Neither patient has experienced further gastrointestinal bleeding; one
      patient has been followed for 27 months. Endoscopic band ligation is an
      alternative and attractive treatment modality for Dieulafoy's lesions.

PMID- 10201489
TI  - Coexisting carcinoid tumors in familial adenomatous polyposis-associated upper
      intestinal adenomas.
AB  - Upper gastrointestinal polyps and extraintestinal tumors are well recognized in
      association with familial adenomatous polyposis (FAP). Although carcinoid tumors
      have been reported in association with sporadic colonic neoplasms and ulcerative
      colitis, to date, carcinoids have not been reported in association with FAP. We
      report a patient with FAP who has recurrent carcinoid tumors located at the bases
      of duodenal adenomas. The genetic basis of carcinoid neoplasms is still
      uncertain. This report may represent the clinical effect of the APC gene mutation
      on the enterochromaffin cell line manifesting as recurrent carcinoid tumors in
      physical association with intestinal adenomas. Future genetic analysis and
      epidemiological studies may be of value in determining whether a true association
      exists.

PMID- 10201491
TI  - Acute abdominal pain as a leading symptom for Degos' disease (malignant atrophic
      papulosis).
AB  - We report a case of a 16-yr-old white female patient with acute abdominal pain
      due to visceral involvement of Degos' disease that required extensive small bowel
      resection. Skin manifestations of her disease had been present for 2 yr before
      the correct diagnosis. She died as a result of central nervous system involvement
      from Degos' disease.

PMID- 10201490
TI  - Persistent hypertransaminasemia as the presenting feature of celiac disease.
AB  - Asymptomatic persistent hypertransaminasemia unrelated to hepatitis viral
      infection is a common cause of referral to the hepatologist. Less frequent liver
      diseases should then be considered, as well as extrahepatic-origin
      hypertransaminasemia. Celiac disease, although it has repeatedly been reported as
      a cause of persistent hypertransaminasemia, is often not included in its
      differential diagnosis in the absence of the classic malabsorption syndrome. We
      present the cases of four patients sent to a liver unit for evaluation of
      persistent hypertransaminasemia in whom celiac disease was finally discovered.
      Our report highlights the importance of including celiac disease in list of
      conditions potentially responsible for chronic hypertransaminasemia of unknown
      cause.

PMID- 10201492
TI  - Pericarditis associated with inflammatory bowel disease: case report.

PMID- 10201493
TI  - A double stomach in an adult.
AB  - Gastric duplication cysts are uncommon congenital anomalies and are rarely
      diagnosed in adults. We present a unique case of a communicating type gastric
      duplication in a young woman with the multimodality imaging findings including
      barium examination, CT, and endoscopy. The morphological criteria for diagnosis
      of duplication cyst suggested pathogenetic mechanisms for its formation as well
      as clinical presentation. Associated pathologies are reviewed.

PMID- 10201494
TI  - Esophageal adenocarcinoma--is Barrett's truly to blame?

PMID- 10201495
TI  - The bald truth.

PMID- 10201496
TI  - Noninvasive "colonoscopy"--fact or fiction?

PMID- 10201497
TI  - Early feeding after percutaneous endoscopic gastrostomy: just do it.

PMID- 10201498
TI  - Cost and cost-effectiveness: consistent terminology is needed.

PMID- 10201499
TI  - A new technique for removing displaced esophageal metal stents.

PMID- 10201500
TI  - Spontaneous bacterial peritonitis due to Pasturella multocida without animal
      exposure.

PMID- 10201501
TI  - Caffeine-assisted chemotherapy for colonic leiomyosarcoma.

PMID- 10201502
TI  - Is poor sanitation a risk factor for developing Crohn's disease?

PMID- 10201503
TI  - Colon cancer in young Egyptian patients.

PMID- 10201504
TI  - Japanese electro-acustim in the treatment of chronic hiccups.

PMID- 10201505
TI  - Clostridium difficile colitis.

PMID- 10201506
TI  - Visceral larva migrans and pyogenic liver abscess.

PMID- 10201507
TI  - Migraine in children and Helicobacter pylori.

PMID- 10201508
TI  - Detection of Helicobacter pylori infection.

PMID- 10201509
TI  - A rare entity: cutaneous metastasis from gastric adenocarcinoma.

PMID- 10201510
TI  - Acute hepatitis related to omeprazole.

PMID- 10201511
TI  - Hepatitis G virus and HCV related extrahepatic disease.

PMID- 10201513
TI  - Esophageal carcinoma in a 17-year-old man.

PMID- 10201512
TI  - Colorectal adenomateous polyps and Helicobacter pylori infection.

PMID- 10201514
TI  - Introduction: the emerging roles of gemcitabine and MTA in the treatment of non
      small cell lung cancer.

PMID- 10201515
TI  - Chemotherapy for non-small cell lung cancer: have we reached a new plateau?
AB  - The last decade has seen the introduction of several new chemotherapeutic agents
      that have activity against non-small cell lung cancer (NSCLC) and produce single
      agent response rates of > or = 20% in previously untreated patients with advanced
      tumors. Furthermore, the results of phase I-II trials have shown that the agents
      can be combined safely with cisplatin or carboplatin and that most combinations
      result in response rates of 35% to 40% or more. Gemcitabine, paclitaxel,
      vinorelbine, and tirapazamine have all been studied in combination with cisplatin
      in trials that compared the combinations with cisplatin alone. All trials
      reported response rates that were significantly higher for the combination arm
      and, with the exception of the paclitaxel trial, median and 1-year survival rates
      were also significantly greater. Vinorelbine as a single agent was compared with
      vinorelbine in combination with cisplatin in three studies. Although response and
      survival rates were longer for the combination arms, single-agent vinorelbine
      produced median survivals of longer than 30 weeks in all trials and a 1-year
      survival rate of 30% in one study. Single-agent gemcitabine was compared with the
      combination of etoposide and cisplatin in two trials. In each study, the response
      to gemcitabine was equal to that of the combination arm, and the 1-year survival
      rate was actually superior for the single-agent gemcitabine arm. Combinations of
      the new agents with cisplatin or carboplatin also have been evaluated in
      randomized phase III trials and compared with standard chemotherapy regimens for
      the treatment of NSCLC. The vinorelbine/cisplatin combination was found to be
      superior to vindesine/cisplatin. Paclitaxel/cisplatin and gemcitabine/cisplatin
      were both found to be superior to etoposide/cisplatin. Survival gains have been
      modest, with median survival ranging from approximately 8 to 10 months and 1-year
      survival rates with the new regimens ranging from 32% to 41%. The new
      chemotherapy regimens have resulted in modest benefit and have set a new standard
      for the treatment of advanced NSCLC.

PMID- 10201516
TI  - Gemcitabine and carboplatin in combination: an update of phase I and phase II
      studies in non-small cell lung cancer.
AB  - Gemcitabine has demonstrated single-agent activity in advanced, incurable non
      small cell lung cancer, yielding response rates of > or =20%. In combination with
      cisplatin, response rates of 30% to 60% and encouraging survival have been
      observed. Carboplatin causes much less nonhematologic toxicity than cisplatin. In
      a phase III Eastern Cooperative Oncology Group trial, initial therapy with
      carboplatin yielded superior survival in advanced non-small cell lung cancer
      compared with cisplatin combinations and other cisplatin analogs, despite a lower
      response rate. Thus, studies designed to identify optimal dose schedules for a
      combination of gemcitabine plus carboplatin are clearly warranted. Carmichael et
      al from the United Kingdom have identified a maximum tolerated dose of
      carboplatin of area under the curve of 5.2 mg/mL/min administered on day I
      followed by gemcitabine 1,000 mg/m2 on days 1, 8, and 15 of a 28-day cycle. This
      combination produced a response rate of 31% and a median survival of 10.5 months
      in 13 evaluable patients. A subsequent phase I evaluation reversing the
      carboplatin and gemcitabine sequence (gemcitabine preceding carboplatin on day 1)
      demonstrated no difference in toxicities, pharmacodynamics, or maximum tolerated
      dose. Other investigators have identified similar promising results with this
      regimen, although one North American investigator has observed untoward toxicity
      in a small number of patients using a standard 28-day dose schedule with
      gemcitabine administered on days, 1, 8, and 15. Day-15 gemcitabine dosing is
      problematic and may contribute to excessive thrombocytopenia when gemcitabine is
      combined with carboplatin. The ongoing phase I/II trials reviewed here have
      focused on a compressed 21-day schedule, with carboplatin administered every 3
      weeks and gemcitabine given on days 1 and 8 only.

PMID- 10201517
TI  - Gemcitabine plus taxane combinations in non-small cell lung cancer.
AB  - Among the relatively new cytotoxic agents that are active in non-small cell lung
      cancer, gemcitabine and the taxanes (paclitaxel and docetaxel) are certainly of
      particular interest due to their essentially nonoverlapping toxicities and single
      agent activities, which compare favorably with single-agent cisplatin. For these
      reasons, new combinations including these agents are being tested in dose-finding
      studies in phase II and III trials. Combinations of gemcitabine with a taxane,
      with or without a platinum compound, represent new and promising regimens for the
      treatment of non-small cell lung cancer and other tumor types.

PMID- 10201518
TI  - Triplet chemotherapy with gemcitabine, a platinum, and a third agent in the
      treatment of advanced non-small cell lung cancer.
AB  - Cisplatin-based chemotherapy regimens were shown to prolong survival, relieve
      symptoms, and improve quality of life in a cost-effective manner in patients with
      advanced non-small cell lung cancer. New chemotherapeutic agents introduced in
      the 1990s, such as gemcitabine, paclitaxel, docetaxel, vinorelbine, and
      irinotecan, were shown to be as effective or more effective than cisplatin. The
      doublet combination of these new agents with cisplatin or carboplatin was more
      active than either as single agents, and randomized trials showed that new
      combinations such as gemcitabine/ cisplatin, vinorelbine/cisplatin, and
      paclitaxel/cisplatin were preferred to cisplatin alone or to etoposide/cisplatin.
      Gemcitabine has a mild toxicity profile that allows it to be combined easily in
      triplet combinations with other doublets. Phase I-II trials of such triplet
      combinations show that each drug can be given safely in full dosage. Preliminary
      efficacy results of these gemcitabine-based triplet combinations are encouraging.
      Randomized trials comparing triplets such as gemcitabine/paclitaxel/carboplatin
      with the corresponding doublets are indicated.

PMID- 10201519
TI  - Overview of MTA in the treatment of non-small cell lung cancer.
AB  - While advanced non-small cell lung cancer is a malignancy which remains largely
      refractory to chemotherapy, the 1990s have seen gains in both the number of
      agents available as well as the frequency of use of these agents in the treatment
      of non-small cell lung cancer. This report reviews several studies of MTA
      (multitargeted antifolate, LY23 1514), a novel antifolate, as first- and second
      line treatment. MTA has been tested in advanced non-small cell lung cancer in a
      variety of patient populations, including those who have received no prior
      chemotherapy, those who have relapsed following prior platinum-containing
      therapy, and those who have relapsed following prior chemotherapy which did not
      contain platinum. In both groups MTA was found to be active, its activity in
      chemonaive patients was comparable (14%-23%) to currently used new drugs like
      taxanes and gemcitabine. Additionally, MTA has been studied in combination with
      cisplatin in patients who are chemotherapy-naive, with a response rate (42%)
      comparable to other modern combination regimens. Preliminary data appear
      promising and will be discussed.

PMID- 10201521
TI  - Animal models of psoriasis - what can we learn from them?
AB  - Research into the pathogenesis of psoriasis has been hampered by the lack of an
      animal disease resembling this common human skin disorder. Over the past few
      years, however, various rodent models that mirror aspects of the psoriatic
      phenotype and pathogenesis have become available. Here, the most prominent models
      are compared with human psoriasis and potential uses for psoriasis research are
      reviewed. Asebia (ab), flaky skin (fsn), and chronic proliferative dermatitis
      (cpd) are spontaneous mouse mutations with psoriasiform skin alterations of
      unclear pathogenesis. Transgenic mice with cutaneous overexpression of cytokines,
      such as interferon-gamma, interleukin-1alpha, keratinocyte growth factor,
      transforming growth factor-alpha, interferon-6, vascular endothelial growth
      factor, or bone morphogenic protein-6, are valuable tools for studying in vivo
      effects of individual cytokines in the pathogenesis of psoriasiform features.
      Psoriasiform lesions also were seen in beta2-integrin hypomorphic mice
      backcrossed to the PL/J strain and in beta1-integrin transgenic mice. A T cell
      based immunopathogenesis of psoriasiform features was shown in a form of graft
      versus-host disease in scid/scid mice reconstituted with CD4+/CD45RB(hi) T
      lymphocytes as well as in HLA-B27/hbeta2m transgenic rats, demonstrating that
      dysregulated T cells can induce psoriasiform skin alterations without a primary
      epithelial abnormality. Finally, xenotransplantation models using human skin
      grafted on to immunodeficient mice are attractive, as different cell types and
      some environmental factors leading to psoriasiform features may be studied in
      human tissue. Overall, although there is no animal model imitating psoriasis
      completely, many aspects of this common human skin disorder are mirrored in the
      currently available models and psoriatic plaques can be created in
      xenotransplantation models.

PMID- 10201522
TI  - Structure and function of hemidesmosomes: more than simple adhesion complexes.
AB  - The attachment of cells to the extracellular matrix is of crucial importance in
      the maintenance of tissue structure and integrity. In stratified epithelia such
      as in skin as well as in other complex epithelia multiprotein complexes called
      hemidesmosomes are involved in promoting the adhesion of epithelial cells to the
      underlying basement membrane. In the past few years our understanding of the role
      of hemidesmosomes has improved considerably. Their importance has become apparent
      in clinical conditions, in which absence or defects of hemidesmosomal proteins
      result in devastating blistering diseases of the skin. Molecular genetic studies
      have increased our knowledge of the function of the various components of
      hemidesmosomes and enabled the characterization of protein-protein interactions
      involved in their assembly. It has become clear that the alpha6beta4 integrin, a
      major component of hemidesmosomes, is able to transduce signals from the
      extracellular matrix to the interior of the cell, that critically modulate the
      organization of the cytoskeleton, proliferation, apoptosis, and differentiation.
      Nevertheless, our knowledge of the mechanisms regulating the functional state of
      hemidesmosomes and, hence, the dynamics of cell adhesion, a process of crucial
      importance in development, wound healing or tumor invasion, remains limited. The
      aims of this review are to highlight the recent progresses of our knowledge on
      the organization and assembly of hemidesmosomes, their involvement in signaling
      pathways as well as their participation in clinical pathologic conditions.

PMID- 10201523
TI  - The iron regulatory protein can determine the effectiveness of 5-aminolevulinic
      acid in inducing protoporphyrin IX in human primary skin fibroblasts.
AB  - The level of endogenous photosensitiser, protoporphyrin IX (PPIX), can be
      enhanced in the cells by 5-aminolevulinic acid (ALA). We investigated the effect
      of critical parameters such as growth state of the cells and availability of
      intracellular iron in modulating the level of PPIX, in human primary cultured
      skin fibroblasts (FEK4) maintained either in exponentially growing or growth
      arrested phase, following treatment with ALA. The addition of ALA to
      exponentially growing cells increased the level of PPIX 6-fold relative to
      control cells; however, in growth-arrested cells the same treatment increased the
      level of PPIX up to 34-fold. The simultaneous addition of the hydrophilic iron
      chelator Desferal with ALA, boosted the level of PPIX up to 47-fold in growing
      cells and up to 42-fold in growth-arrested cells, suggesting that iron is
      limiting under the latter conditions. The strict dependence of PPIX enhancement
      on free available iron levels was examined by the level of activation of iron
      regulatory protein in band shift assays. This analysis revealed that the basal
      level of iron regulatory protein in growth-arrested cells was 6-fold higher than
      in growing cells, reflecting the influence of the free available iron pool in
      exponentially growing cells. Interestingly, the same ratio was found between the
      basal level concentration of PPIX in growing and growth-arrested cells. We
      propose that iron regulatory protein activation could serve as a marker for
      developing photodynamic therapy protocols because it identifies cells and tissues
      with a propensity to accumulate PPIX and it is therefore likely to predict the
      effectiveness of such therapies.

PMID- 10201525
TI  - Activin A induces terminal differentiation of cultured human keratinocytes.
AB  - Activin A, a member of the TGFbeta-superfamily, is well known to play important
      roles in the growth and differentiation of various target cells. We have
      previously demonstrated that activin A is produced at an early stage of
      cultivation at both the protein and the mRNA levels in cultured human
      keratinocytes. In this study, the effects of activin A on differentiation and
      proliferation of human keratinocytes were examined. Activin A (> or =1 nM)
      induced cornified envelope formation and the synthesis of loricrin, keratin 1,
      involucrin, and transglutaminase 1. In addition, transglutaminase activity and
      mRNA level of transglutaminase 1 were increased by activin A. [3H]Thymidine
      incorporation and cell number were reduced by activin A (> or =1 nM) compared
      with control, suggesting an inhibitory effect of activin A on cell proliferation.
      On the basis of these findings, it is likely that activin A contributes to
      differentiation and suppression of proliferation in human keratinocytes.

PMID- 10201524
TI  - Induction of TR4 orphan receptor by retinoic acid in human HaCaT keratinocytes.
AB  - Human TR4 orphan receptor (TR4) can modulate the transcriptional activity of the
      reporter gene containing an AGGTCA direct repeat-hormone response element. Here
      we studied the potential role of TR4 in human HaCaT keratinocytes. Using a
      chloramphenicol acetyl-transferase reporter gene assay, it was shown that TR4 can
      suppress retinoic acid-induced transactivation by 47.3% in human HaCaT
      keratinocytes. Electrophoretic mobility shift assay indicated that this
      suppression may be due to TR4 binding with higher affinity to the retinoic acid
      response element than retinoid receptors. Western blot analysis further suggested
      that retinoic acid can increase the expression of TR4 protein in human HaCaT
      keratinocytes, indicating that TR4 acts as a negative feedback modulator for
      retinoic acid action. Interestingly, TR4 expression is increased in normal human
      keratinocytes when substituting a low calcium medium with a high calcium medium.
      Together, our data suggested, for the first time, that an orphan receptor, such
      as TR4, may play an important part in retinoid-mediated signaling pathways in
      human keratinocytes, providing a new insight into keratinocyte biology.

PMID- 10201526
TI  - A substance p agonist acts as an adjuvant to promote hapten-specific skin
      immunity.
AB  - Because substance p (SP) has been reported to be released from cutaneous sensory
      nerve endings after hapten application, we determined whether SP participates in
      contact hypersensitivity (CH) induction by using a SP agonist, GR73632 or delta
      Aminovaleryl [Pro9, N-Me-Leu10]-substance P(7-11) and a SP antagonist, spantide
      I. When injected intradermally, SP agonist enhanced CH induced by conventional,
      but not optimal, sensitizing doses of hapten. By contrast, SP antagonist
      inhibited the induction of CH by optimal sensitizing doses of hapten. Moreover,
      SP agonist promoted CH induction and prevented tolerance when hapten was painted
      on skin exposed to acute, low-dose ultraviolet-B radiation. Intradermally
      injected SP agonist altered neither the density nor the morphology of epidermal
      Langerhans cells, implying that SP agonist enhanced the generation of hapten
      specific immunogenic signals from the dermis. It is proposed that SP is a natural
      "adjuvant" that promotes the induction of CH within normal skin. Although
      exogenous SP agonist can prevent impaired CH and tolerance after ultraviolet-B
      radiation, the susceptibility of native SP to local neuropeptidases renders the
      neuropeptide unable to prevent the deleterious effects of ultraviolet-B radiation
      on cutaneous immunity.

PMID- 10201527
TI  - A central role of Bcl-X(L) in the regulation of keratinocyte survival by
      autocrine EGFR ligands.
AB  - The epidermal growth factor receptor has multiple roles in epidermal biology
      relating to growth, migration, and, as shown recently, survival of keratinocytes.
      In cultured keratinocytes activation of the epidermal growth factor receptor
      upregulates expression of Bcl-x(L), an anti-apoptotic Bcl-2 homolog. The
      functional contribution of epidermal growth factor receptor-dependent Bcl-x(L)
      expression to keratinocyte survival is poorly understood. Here we demonstrate
      that inhibition of the epidermal growth factor receptor tyrosine kinase activity
      with either an epidermal growth factor receptor antagonistic monoclonal antibody
      (MoAb 425) or an epidermal growth factor receptor-selective tyrosine kinase
      inhibitor (AG 1478) downregulated Bcl-x(L) expression in normal human
      keratinocytes but had no effect on expression of the pro-apoptotic Bcl-2 homologs
      Bad, Bak, and Bax. Bovine pituitary extract and insulin partially alleviated
      both, downregulation of Bcl-x(L) expression and cell death upon epidermal growth
      factor receptor inhibition. Forced expression of Bcl-x(L) attenuated cell death
      of immortalized keratinocytes (HaCaT) induced by either forced suspension
      (anoikis) or by epidermal growth factor receptor blockade. These results
      demonstrate that epidermal growth factor receptor-dependent signaling pathways
      control the balance of pro-apoptotic and anti-apoptotic Bcl-2 family members
      expressed in normal keratinocytes. Inappropriate survival supported by aberrant
      signaling through the epidermal growth factor receptor may contribute to the
      pathogenesis of psoriasis and of squamous cell carcinomas.

PMID- 10201528
TI  - UVB irradiation stimulates deposition of new elastic fibers by modified
      epithelial cells surrounding the hair follicles and sebaceous glands in mice.
AB  - UVB irradiation stimulates the synthesis of elastin in the skin of humans and
      experimental animals. In this study we localized the site and the cells that are
      responsible for the synthesis of murine dermal elastic fibers. SKH-1 hairless
      mice were irradiated with UVB and the skin removed for light microscopy, electron
      microscopy, in situ hybridization, immunohistochemistry, and biochemical studies.
      In response to chronic low doses of UVB there was an initial moderate increase in
      tropoelastin mRNA in the papillary dermis. By contrast, there was a continuous
      marked elevation of collagen alpha1(I) message localizing to sites of
      inflammatory cell influx throughout the upper and lower dermis. After 25 wk of UV
      irradiation there was a 2-fold increase in skin elastin, yet total collagen
      remained unchanged. Serial desmosine analysis from en face sections indicated the
      increase in elastin content was due to dermal elastic fibers, an increase in the
      size and number of the dermal cysts, and an increase in subpanniculus elastic
      fibers. Elastin stains of en face sections suggested that the elastic fibers in
      the upper dermis were exclusively derived from cells lining the epithelial root
      sheath and sebaceous glands. In response to UV irradiation, the elastic fibers
      increased in number and size, wrapping around these structures and aligning in
      both directions as long fibers parallel to the body axis. Electron micrographs
      indicated that modified epithelial cells in close proximity to the flattened
      epithelial cells that encircled the root sheath and sebaceous glands were the
      source of the elastic fibers.

PMID- 10201529
TI  - Animal model of sclerotic skin. I: Local injections of bleomycin induce sclerotic
      skin mimicking scleroderma.
AB  - We have established a mouse model for scleroderma induced by repeated local
      injections of bleomycin (BLM). Daily injection of BLM at a dose of >10 microg per
      ml for 4 wk induced histologic changes of dermal sclerosis, but not fibrosis,
      with thickened and homogenous collagen bundles and cellular infiltrates in BALB/C
      mice, whereas clinical signs of scleroderma were not apparent. In addition, lung
      fibrosis was also induced preceding the cutaneous changes. Sclerotic changes were
      not found in other sites of the skin distant from the injection site. Dermal
      sclerosis could also be induced by injecting BLM only every other day. The
      sclerotic changes of the dermis were sustained after ceasing BLM applications for
      at least 6 wk. Mast cells gradually increased in number as the sclerotic changes
      developed. Marked degranulation of mast cells was observed with elevated
      histamine release. The amount of hydroxyproline in skin was significantly
      increased at 4 wk of BLM treatment as compared with that in untreated or
      phosphate-buffered saline-treated mice. Anti-nuclear antibody was detected in
      serum of BLM-treated mice. Transforming growth factor-beta1 mRNA was detected at
      an early phase, while transforming growth factor-beta2 mRNA was strongly
      expressed at 4 wk when the sclerotic features were prominent. These results
      suggest that dermal sclerosis induced by BLM closely resembles systemic sclerosis
      both histologically and biochemically. Our mouse model can provide a powerful
      tool of inducing dermal sclerosis to examine the pathogenesis and the therapeutic
      approach of scleroderma.

PMID- 10201530
TI  - Proliferation and mitogenic response to PDGF-BB of fibroblasts isolated from
      chronic venous leg ulcers is ulcer-age dependent.
AB  - Several pathophysiologic mechanisms have been proposed to explain slow-healing
      leg ulcers, but little is known about the growth behavior of cells in these
      wounds. Platelet-derived growth factor-BB applied topically to chronic wounds has
      shown beneficial effects, although the effects have been less pronounced than
      would have been expected based on studies on acute wounds. The objective of this
      study was to compare fibroblasts in culture obtained from chronic wounds (non
      healing chronic venous leg ulcers), acute wounds and normal dermis regarding
      growth, mitogenic response to platelet-derived growth factor-BB and levels
      ofplatelet-derived growth factor alpha-receptor and beta-receptor. Fibroblasts
      were obtained by an explant technique and expanded in vitro using fibroblast
      growth medium supplemented with 10% fetal bovine serum and used for the assays at
      their third passage. Growth of chronic wound fibroblasts (n = 8) was
      significantly (p < 0.05) decreased compared with those from acute wounds (n = 10)
      and normal dermis (n = 5). Fibroblasts from ulcers older than 3 y grew
      significantly (p < 0.01) slower than those from ulcers that had been present for
      less than 3 y. Morphology and size of fibroblasts from the oldest chronic wounds
      deviated substantially from those of acute wounds and normal dermis, and
      resembled in vitro aged or senescent fibroblasts. Mitogenic response of chronic
      wound fibroblasts to human recombinant platelet-derived growth factor-BB was also
      reduced with ulcer age. No significant differences were found in the amount of
      either platelet-derived growth factor alpha-receptor or beta-receptor among the
      three groups. The features decreased growth related to ulcer age, altered
      morphology, and reduced response to platelet-derived growth factor, indicating
      that fibroblasts in some chronic wounds have approached or even reached the end
      of their lifespan (phase III). This might provide one explanation for the non
      healing state and therapy resistance to topical platelet-derived growth factor-BB
      of some venous leg ulcers.

PMID- 10201531
TI  - Highly persistent label-retaining cells in the hair follicles of mice and their
      fate following induction of anagen.
AB  - We have identified some unusually persistent label-retaining cells in the hair
      follicles of mice, and have investigated their role in hair growth. Three
      dimensional reconstruction of dorsal underfur follicles from serial sections made
      14 mo after complete labeling of epidermis and hair follicles in neonatal mice
      disclosed the presence of highly persistent label-retaining cells associated with
      the first-generation follicle involved in the production of the first wave of
      hairs, commonly called the bulge. The label-retaining cells were most often found
      on the ventral surface of the first-generation follicle, five cell positions from
      the base, near the attachment site of the arrector pilorum muscle. No label
      retaining cells were found in the hair canal, sebaceous gland, or hair germ.
      These label-retaining cells remained in the follicle following induction of
      anagen by plucking of the hairs. Surprisingly, they were not part of the first
      wave of mitotic activity following plucking, but instead underwent mitosis
      beginning 42 h after plucking. Label-retaining cells or their labeled daughters
      were not found in the hair germs through 48 h following induction of anagen by
      plucking, but instead remained in their subsebaceous follicular location even
      upon completion of the hair growth cycle 21 d later. These label-retaining cells
      are, therefore, unlikely to contribute to the formation of a new anagen follicle.

PMID- 10201532
TI  - Inhibition of allergic contact dermatitis to DNCB but not to oxazolone in
      interleukin-4-deficient mice.
AB  - The role of interleukin-4 as a regulator of immune responses in the skin is
      investigated with regard to the outcome of contact hypersensitivity reaction in
      interleukin-4-deficient BALB/C mice. In previous studies conflicting results were
      obtained concerning the role of interleukin-4 in contact hypersensitivity
      reactions supporting either a proinflammatory or rather an inhibitory function of
      this cytokine. Interleukin-4 deficient BALB/C mice sensitized to 2,4
      dinitrochlorobenzene showed after challenge a significant reduction in magnitude
      and duration of the contact hypersensitivity response in comparison with wild
      type mice. This attenuation was accompanied by a significant reduction of edema
      and cellular infiltrates in the dermis and a lacking induction of IL-10 mRNA
      expression in skin. Also, adoptive transfer experiments revealed that BALB/C mice
      failed to exhibit contact hypersensitivity after injection of lymph node cells
      obtained from sensitized interleukin-4 deficient mice. To examine further the
      role of the contact allergen used to induce the contact hypersensitivity
      response, mice were also sensitized and challenged with Oxazolone. Here a similar
      magnitude and duration of contact hypersensitivity in both the interleukin-4
      deficient mice and BALB/C control mice was observed. This indicates that the
      contact hypersensitivity response to 2,4-dinitrochlorobenzene and Oxazolone may
      partly evolve on different pathways being dependent and independent of
      interleukin-4. Our results clearly show that the complete loss of endogenous
      interleukin-4 expression in BALB/C mice is associated with an impaired
      manifestation of contact hypersensitivity response to 2,4-dinitrochlorobenzene,
      implying an important proinflammatory function of this cytokine.

PMID- 10201533
TI  - Regulation of keratin 9 in nonpalmoplantar keratinocytes by palmoplantar
      fibroblasts through epithelial-mesenchymal interactions.
AB  - Palms and soles differ from other body sites in terms of clinical and histologic
      appearance, response to mechanical stress, and the distribution of keratin 9.
      Because keratin 9 is exclusively expressed in the palmoplantar suprabasal
      keratinocyte layers, it is considered a differentiation marker of palms and
      soles. We studied palmoplantar mesenchymal influences on keratin 9 induction in
      nonpalmoplantar epidermis. Although palmoplantar keratinocytes when cultured
      alone continued to express keratin 9 mRNA in 12 (100%) of 12 cultures,
      nonpalmoplantar keratinocytes did not express it in 16 of 17 cultures. Although
      nonpalmoplantar keratinocytes did not express keratin 9 mRNA when cultured with
      nonpalmoplantar fibroblasts, they did express it within 2 h in cocultures with
      palmoplantar fibroblasts derived from papillary dermis. Grafting of these
      coculture sheets on severe combined immunodeficient mice resulted in an
      epidermis, which histologically showed hyperkeratosis and acanthosis and
      immunohistochemically expressed keratin 9. Furthermore, pure epidermal sheets
      from nonpalmoplantar skin grafted on the human sole wounds due to burn, injury,
      and the resection of acral lentiginous melanoma, demonstrated adoption of
      palmoplantar phenotype and expressed keratin 9. Our report indicates extrinsic
      keratin 9 regulation by signals from dermal fibroblasts. This is also the first
      to suggest the possibility of treating palmoplantar wounds with nonpalmoplantar
      epidermis, which is much easier to obtain and harvest.

PMID- 10201534
TI  - Reconstruction of a human skin equivalent using a spontaneously transformed
      keratinocyte cell line (HaCaT).
AB  - Reconstruction of a skin equivalent using an immortalized human keratinocyte
      line, HaCaT, was investigated in an attempt to generate an in vitro system
      representative for human skin. Three different substrates were used to establish
      air-exposed cultures of HaCaT cells: de-epidermized dermis, collagen gels, and
      filter inserts. Effects of variations in culture conditions on tissue morphology,
      on the expression of proliferation-specific and differentiation-specific protein
      markers, and on lipid profiles were investigated. When grown at the air-liquid
      interface HaCaT cells initially developed a multilayered epithelium, but during
      the course of culture marked alterations in tissue architecture were observed.
      Ultrastructurally, a disordered tissue organization was evident as judged from
      the presence of rounded cells with abnormally shaped nuclei. Keratins K1 and K10
      were irregularly expressed in all cell layers, including stratum basale. Staining
      of K6/K16 was evident in all cell layers. Locally, basal and suprabasal cells
      were positive for K4 and additionally expressed K13 and K19. The cornified
      envelope precursors were expressed only in older cultures (>2 wk after air
      exposure), except for transglutaminase and small proline rich protein 1, which
      were irregularly expressed in both early and older cultures. In addition, HaCaT
      cells showed an impaired capacity to synthesize lipids that are necessary for a
      proper barrier formation as indicated by the absence of free fatty acids and a
      very low content and incomplete profile of ceramides. Our data demonstrate that
      the ultimate steps of terminal differentiation in HaCaT cells do not occur
      irrespective of the type of substrate or the culture conditions.

PMID- 10201535
TI  - Enhanced expression of human metalloelastase (MMP-12) in cutaneous granulomas and
      macrophage migration.
AB  - Accumulation of inflammatory cells such as macrophages may lead to degeneration
      of connective tissue matrix in various skin diseases. Macrophage metalloelastase,
      is a matrix metalloproteinase (MMP-12) capable of degrading elastin as well as
      various basement membrane components. To investigate the role of human macrophage
      metalloelastase in skin, we assessed by in situ hybridization and
      immunohistochemistry 66 specimens representing skin diseases characterized either
      by changes in elastic fibers or by pronounced infiltrations of extravasating and
      migrating macrophages. CD68 immunostaining was performed to identify the human
      macrophage metalloelastase-positive cells and Weigert's Resorcin-Fuchsin staining
      to reveal the status of elastic fibers. We found abundant expression of human
      macrophage metalloelastase mRNA in macrophages in areas devoid of normal elastic
      fibers in granulomatous skin diseases sarcoidosis, necrobiosis lipoidica
      diabeticorum, and granuloma annulare. Positive cells for human macrophage
      metalloelastase protein could be detected in the same regions as well as positive
      immunostaining for urokinase plasminogen activator. Of the other matrix
      metalloproteinases capable of degrading elastin, 92 kDa gelatinase colocalized
      with human macrophage metalloelastase, while 72 kDa gelatinase was produced by
      surrounding fibroblast-like cells. Furthermore, human macrophage metalloelastase
      was expressed by macrophages in areas with disrupted basement membrane, as
      assessed by type IV collagen staining, in pityriasis lichenoides and dermatitis
      herpetiformis. Specimens of anetoderma, acrodermatitis chronica atrophicans and
      pseudoxanthoma elasticum showed no signal for human macrophage metalloelastase.
      Matrilysin was not detected in any of the samples investigated. Our study
      suggests that human macrophage metalloelastase may contribute to elastin
      degradation occurring in granulomatous skin diseases and may aid macrophage
      migration through the epidermal and vascular basement membranes in inflammatory
      disorders.

PMID- 10201536
TI  - A novel substitution in keratin 10 in epidermolytic hyperkeratosis.
AB  - Epidermolytic hyperkeratosis is characterized by tonofilament clumping,
      cytolysis, and blister formation in suprabasal keratinocytes. It has been shown
      that the tonofilament aggregates in these areas are composed of keratin 1 (K1)
      and keratin 10 (K10), and several K1 and K10 point mutations have been identified
      as the molecular basis of epidermolytic hyperkeratosis. In this report we
      identify a novel, single base pair substitution resulting in an amino acid
      exchange from tyrosine to serine at residue 14 within the conserved 1A region of
      K10 (Y14S). This A to C transversion in codon 160 was only present in the
      affected individual and was associated with a very severe disease phenotype. Our
      observations are in agreement with previous reports documenting that this
      tyrosine residue, located at the beginning of the rod domain of type I keratins,
      is particularly sensitive to amino acid substitutions, and that alterations in
      this residue can have deleterious effects on filament assembly and stability.

PMID- 10201538
TI  - Skin type, melanoma, and melanocortin 1 receptor variants.

PMID- 10201537
TI  - Somatic mutations in the Peutz-Jeghers (LKB1/STKII) gene in sporadic malignant
      melanomas.
AB  - Germline mutations in the LKB1/STK11 gene cause characteristic hamartomas and
      freckling to develop in patients with Peutz-Jeghers syndrome (PJS). The
      hamartomas arise as a result of somatic "second hits" at LKB1/STK11 and therefore
      contain a neoplastic element. The origin of the pigmented lesions in PJS is
      unknown and difficult to test, as these are hardly ever biopsied. PJS patients
      are at increased risk of benign and malignant tumors, particularly of the colon,
      breast, pancreas, testis, and ovary, although the increased risk for any one of
      these sites may be quite modest. Somatic LKB1/STK11 mutations have been found,
      albeit at a low frequency, in sporadic tumors of the colon, stomach, ovary, and
      testis. Although PJS patients are not known to have an excess of skin tumors, if
      the freckles of PJS patients are actually small, benign tumors, LKB1/STK11
      mutations must provide these lesions with a selective advantage, and similar
      mutations might also give a selective advantage to related malignant tumors, such
      as melanomas. We have therefore screened 16 melanoma cell lines, 15 primary
      melanomas, and 19 metastases for LKB1/STK11 mutations. Two LKB1/STK11 mutations
      were found: a missense change (Y49D) accompanied by allele loss in a cell line;
      and a missense change (G135R), without a detected mutation in the other allele,
      in a primary tumor. Both these mutations are highly likely to be pathogenic.
      Novel polymorphisms, including an unusual heptanucleotide repeat, were also found
      in introns 2 and 3. LKB1/STK11 mutations occur in a significant minority of
      tumors of several sites, including malignant melanomas.

PMID- 10201539
TI  - Promoter polymorphism at -238 of the tumor necrosis factor alpha gene is not
      associated with early onset psoriasis when tested by the transmission
      disequilibrium test.

PMID- 10201540
TI  - Human epidermal proopiomelanocortin (POMC) cDNA variant is identical to mouse
      POMC cDNA.

PMID- 10201541
TI  - Promising what we can deliver.

PMID- 10201542
TI  - Hip moments during level walking, stair climbing, and exercise in individuals
      aged 55 years or older.
AB  - BACKGROUND AND PURPOSE: Low bone mass of the proximal femur is a risk factor for
      hip fractures. Exercise has been shown to reduce bone loss in older individuals;
      however, the exercises most likely to influence bone mass of the proximal femur
      have not been identified. Net moments of force at the hip provide an indication
      of the mechanical load on the proximal femur. The purpose of this study was to
      examine various exercises to determine which exercises result in the greatest
      magnitude and rate of change in moments of force at the hip in older individuals.
      SUBJECTS AND METHODS: Walking and exercise patterns were analyzed for 30 subjects
      (17 men, 13 women) who were 55 years of age or older (X = 65.4, SD = 6.02, range
      = 55-75) and who had no identified musculoskeletal or neurological impairment.
      Kinematic and kinetic data were obtained with an optoelectronic system and a
      force platform. Results. Of the exercises investigated, only ascending stairs
      generated peak moments higher than those obtained during level walking and only
      in the transverse plane. Most of the exercises generated moments and rate of
      change in moments with magnitudes similar to or lower than those obtained during
      gait. CONCLUSION AND DISCUSSION: Level walking and exercises that generated
      moments with magnitudes comparable to or higher than those obtained during gait
      could be combined in an exercise program designed to maintain or increase bone
      mass at the hip.

PMID- 10201543
TI  - The Lower Extremity Functional Scale (LEFS): scale development, measurement
      properties, and clinical application. North American Orthopaedic Rehabilitation
      Research Network.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to assess the reliability,
      construct validity, and sensitivity to change of the Lower Extremity Functional
      Scale (LEFS). SUBJECTS AND METHODS: The LEFS was administered to 107 patients
      with lower-extremity musculoskeletal dysfunction referred to 12 outpatient
      physical therapy clinics. METHODS: The LEFS was administered during the initial
      assessment, 24 to 48 hours following the initial assessment, and then at weekly
      intervals for 4 weeks. The SF-36 (acute version) was administered during the
      initial assessment and at weekly intervals. A type 2,1 intraclass correlation
      coefficient was used to estimate test-retest reliability. Pearson correlations
      and one-way analyses of variance were used to examine construct validity.
      Spearman rank-order correlation coefficients were used to examine the
      relationship between an independent prognostic rating of change for each patient
      and change in the LEFS and SF-36 scores. RESULTS: Test-retest reliability of the
      LEFS scores was excellent (R = .94 [95% lower limit confidence interval (CI) =
      .89]). Correlations between the LEFS and the SF-36 physical function subscale and
      physical component score were r=.80 (95% lower limit CI = .73) and r = .64 (95%
      lower limit CI = .54), respectively. There was a higher correlation between the
      prognostic rating of change and the LEFS than between the prognostic rating of
      change and the SF-36 physical function score. The potential error associated with
      a score on the LEFS at a given point in time is +/-5.3 scale points (90% CI), the
      minimal detectable change is 9 scale points (90% CI), and the minimal clinically
      important difference is 9 scale points (90% CI). CONCLUSION AND DISCUSSION: The
      LEFS is reliable, and construct validity was supported by comparison with the SF
      36. The sensitivity to change of the LEFS was superior to that of the SF-36 in
      this population. The LEFS is efficient to administer and score and is applicable
      for research purposes and clinical decision making for individual patients.

PMID- 10201544
TI  - The prevalence of low back pain in adults: a methodological review of the
      literature.
AB  - The prevalence of low back pain (LBP) has been reported in the literature for
      different populations. Methodological differences among studies and lack of
      methodological rigor have made it difficult to draw conclusions from these
      studies. A systematic review was done for adult community prevalence studies of
      LBP published from 1981 to 1998. The technique of capture-recapture was performed
      to estimate the completeness of the search strategy used. Established guidelines
      and a methodological scoring system were used to critically appraise the studies.
      Thirteen studies were deemed methodologically acceptable. Differences in the
      duration of LBP used in the studies appeared to affect the prevalence rates
      reported and explain much of the variation seen. It was estimated that the point
      prevalence rate in North America is 5.6%. Further studies using superior methods
      are needed, however, before this estimate can be used with confidence to make
      health care policies and decisions relating to physical therapy.

PMID- 10201545
TI  - Physical therapy for facial paralysis: a tailored treatment approach.
AB  - BACKGROUND AND PURPOSE: Bell palsy is an acute facial paralysis of unknown
      etiology. Although recovery from Bell palsy is expected without intervention,
      clinical experience suggests that recovery is often incomplete. This case report
      describes a classification system used to guide treatment and to monitor recovery
      of an individual with facial paralysis. CASE DESCRIPTION: The patient was a 71
      year-old woman with complete left facial paralysis secondary to Bell palsy. Signs
      and symptoms were assessed using a standardized measure of facial impairment
      (Facial Grading System [FGS]) and questions regarding functional limitations. A
      treatment-based category was assigned based on signs and symptoms. Rehabilitation
      involved muscle re-education exercises tailored to the treatment-based category.
      OUTCOMES: In 14 physical therapy sessions over 13 months, the patient had
      improved facial impairments (initial FGS score= 17/100, final FGS score= 68/100)
      and no reported functional limitations. DISCUSSION: Recovery from Bell palsy can
      be a complicated and lengthy process. The use of a classification system may help
      simplify the rehabilitation process.

PMID- 10201546
TI  - Status of the year 2000 health goals for physical activity and fitness.
AB  - In Healthy People 2000, the national strategy for improving the health of the
      American people by the year 2000, lifestyle factors such as physical inactivity
      are major determinants of chronic disease and disability. Despite the documented
      benefits of exercise in enhancing health and reducing the risk of premature
      death, only 1 of the 13 physical activity and fitness objectives of Healthy
      People 2000 has been met or exceeded. Although progress toward 5 objectives for
      the year 2000 has been made, 3 objectives are actually farther from attainment.
      Coronary heart disease death rates (Objective 1.1) have declined, and the
      prevalence of overweight people (Objective 1.2) has increased. Overall physical
      activity in adults (Objectives 1.3 and 1.4) and strengthening and stretching
      activities in children (Objective 1.6) have increased, but reduction in the
      percentage of sedentary persons (Objective 1.5) has showed no change. The
      proportion of the population adopting sound dietary practices combined with
      regular physical activity to attain appropriate body weight (Objective 1.7) has
      declined. Even though participation in daily school physical education (Objective
      1.8) has shown a decline during the past several years, students who are enrolled
      in physical education classes are spending more time performing physical
      activities (Objective 1.9). The proportion of work sites offering employer
      sponsored physical activity and fitness programs (Objective 1.10) has increased
      substantially, surpassing the year 2000 goal. Data to update progress for
      increasing physical activity levels of children (Objectives 1.3-1.5), community
      exercise facilities (Objective 1.11), clinician counseling about physical
      activity (Objective 1.12), and improvement in personal self-care activities
      (Objective 1.13) are not yet available.

PMID- 10201547
TI  - Sensitivity to change.

PMID- 10201548
TI  - Maintaining quality of life.

PMID- 10201549
TI  - First-degree kinship with young coronary artery disease patients markedly
      increases lipid-level disorders in asymptomatic hypertensives.
AB  - BACKGROUND: Association of hypertension and serum lipid disorders has been
      demonstrated in previous studies. However, there are no investigations about the
      behaviour of serum lipids in asymptomatic hypertensive individuals who are first
      degree relatives of young coronary patients. OBJECTIVE: To determine the degree
      of lipid disorders in Brazilian hypertensive individuals who are first degree
      relatives of young coronary patients. METHODS: There were four study groups, 2 in
      each arm of the study: a) 846 subjects without any evidence of heart disease or
      diabetes who were first degree relatives of patients who underwent coronary
      artery bypass grafting (CABG) surgery before 55 years-of-age. Of these subjects,
      226 individuals were hypertensive (group Hyp F), and 620 were normotensive (group
      Normo F): b) 910 hospital employees without evidence of cardiovascular disease
      and family history of coronary artery disease of whom 152 were hypertensive
      (group Hyp NF), and 758 were normotensive (group Normo NF). Hypertension was
      defined as blood pressure greater than 140/90 mmHg. The following serum lipid
      measurements were performed: total cholesterol, high-density lipoprotein
      cholesterol (HDLC), low-density lipoprtein cholesterol (LDLC), and triglycerides.
      Lipid disorders were defined according to the 2nd Report of the National
      Cholesterol Education Program (NCEP) (total cholesterol>240 mg/dl; LDLC>160
      mg/dl; triglycerides>200 mg/dl). The frequency of lipid disorders in each group
      was calculated. Subjects were classified according to their body mass index (BMI)
      as normal, overweight, or obese. The following statistical analyses were
      performed as indicated: ANOVA (with Tukey's corrections for multiple
      comparisons), chi-square (x2), and odds ratio (OR). RESULTS: Hyp F subjects had
      significantly higher total cholesterol, LDLC and triglyceride levels, and
      significantly lower levels of HDLC than all other groups. There was a higher
      frequency of lipid disorders in Hyp F subjects than in Hyp NF individuals, with a
      significant OR of 1.71 (CI 1.26-2.32) and 2.09 (CI 1.48-2.72) for total
      cholesterol and LDLC respectively. When compared to Normo F subjects, Hyp F
      individuals had significantly higher risk of having lipid disorders: total
      cholesterol (OR=8), LDLC (OR=6), and triglycerides (OR=5). There was a higher
      frequency of obesity among Hyp F patients than in all other groups. The frequency
      of subjects who were overweight or obese was higher in Hyp F than in Hyp NF
      subjects. CONCLUSION: Hypertensive patients who were first degree relatives of
      patients revascularized at a young age had a higher prevalence of lipid
      disorders, particularly higher total cholesterol and LDLC, than hypertensive
      individuals without this family history. These individuals may have a greater
      genetic propensity to develop lipid disorders.

PMID- 10201550
TI  - Readiness to change health behaviours among patients at high risk of
      cardiovascular disease.
AB  - OBJECTIVE: To determine readiness to change dietary intake of fat, physical
      exercise and smoking, using a classification based on the stages of change model,
      among patients in a primary care population selected to have greater than normal
      risk of coronary heart disease. METHODS: We recruited 883 patients from general
      practices in the south of England who had one or more of the following
      cardiovascular risk factors: current cigarette smoking, total cholesterol level
      6.5-9.0 mmol/l and a body mass index of 25-35 kg/m2 coupled with a lack of
      regular physical exercise. Measures of cardiovascular risk factors were obtained,
      together with questionnaire measures of stage of readiness to change smoking
      behaviour, dietary intake of fat and level of physical exercise. RESULTS:
      Patients with high cholesterol levels had a different degree of readiness to
      reduce dietary fat from that of those with low cholesterol levels. Patients who
      were overweight and inactive reported a greater readiness to increase their
      physical activity than did those who were not overweight and not inactive.
      Readiness to change any of the three behaviours was not affected by the presence
      of more than one modifiable risk factor. However, patients who were contemplating
      or preparing to stop smoking were also more ready to increase physical activity
      than were those who were not considering stopping smoking. CONCLUSIONS: Risk
      classification has an impact upon patients' readiness to change modifiable
      cardiovascular risk behaviours. The relationships between readiness to change
      various behaviours suggest that there are synergies in counselling strategies and
      methods of identifying patients who might be especially responsive.

PMID- 10201551
TI  - The effect of age and lifestyle factors on plasma levels of apolipoprotein E.
AB  - BACKGROUND: The plasma concentration of apolipoprotein E might be an important
      risk factor for various chronic diseases, including coronary heart disease.
      OBJECTIVE: To investigate the role of lifestyle-related factors in determining
      concentrations of apolipoprotein E. METHODS: The independent effects of age and
      several lifestyle-related factors [body mass index (BMI), smoking, consumption of
      alcohol, physical activity, educational level and poly-unsaturated:saturated
      fatty acid intake ratio in diet] on the apolipoprotein E concentration were
      assessed for a sample of 757 middle-aged working men. Multiple log-linear
      regression models were fitted with additional correction for the apolipoprotein E
      polymorphism. RESULTS: The overall mean plasma concentration of apolipoprotein E
      was 3.44 mg/dl with mean levels varying from 2.42 mg/dl in men with the E4/4
      phenotype to 8.32 mg/dl in men in the E2/2 group. In multivariate analysis
      apolipoprotein E levels were found to be significantly positively correlated to
      BMI (P<0.0001) and consumption of alcohol (P=0.04). The effect of age on the
      apolipoprotein E concentration was significantly quadratic (P=0.02) with highest
      levels found in the men aged 40-44 years (levels 13.3% greater than those in the
      men aged 35-39 years). Subjects with BMI in the range 27-30 kg/m2 had on average
      a 16.4% higher apolipoprotein E concentration than did men in the group with BMI
      lower than 23 kg/m2. This adjusted proportional increase amounted to 22.6% for
      the severely obese subjects (BMI>30 kg/m2). The independent effect of current
      smoking was only of borderline stat stical significance. CONCLUSIONS: These
      results indicate that age and lifestyle-related factors, such as BMI and to a
      lesser extent consumption of alcohol and smoking, should be taken into account as
      possible confounders in the study of the plasma concentration of apolipoprotein E
      as a risk factor for coronary heart disease.

PMID- 10201552
TI  - Patients' and physicians' assessment of risks associated with hypertension and
      benefits from treatment.
AB  - BACKGROUND: Perceptions of effects of a medical regimen may affect patients'
      adherence to therapy. OBJECTIVE: To assess concordance between patients' and
      physicians' estimations of the risks of hypertension and benefits of treatment
      during a regular follow-up appointment. DESIGN: A population-based Swedish
      multicentre study. Patients were included consecutively from a randomized
      selection of centres (55 primary health care centres and 11 clinics of internal
      medicine). METHODS: A questionnaire was given to 1013 patients undergoing their
      individually prescribed antihypertensive therapy and 212 physicians who were
      caring for these patients. RESULTS: Without therapy, patients perceived the risks
      of cardiovascular complications to be higher than did their physicians. Patients
      were not aware that an increasing number of risk factors has an impact on the
      risk of complications. Patients furthermore rated the benefits of treatment
      higher than did their physicians (P<0.001). Of the patients, 14% had blood
      pressures < or = 140/90 mmHg. Most of the patients (61%) were not aware of their
      target blood pressure. However, when the target pressure was communicated to
      patients by the physician, patients remembered it accurately. The patients were
      generally not willing to trade even minor side effects from antihypertensive
      therapy for benefits of treatment. CONCLUSIONS: There was a high degree of
      inconsistency between patients' and physicians' estimations of risks of
      hypertension. Patients estimated the effects of treatment to be more beneficial
      than did their physicians.

PMID- 10201554
TI  - Effects of cessation of smoking after myocardial infarction.
AB  - Smoking is an important risk factor for myocardial infarction, but not for
      uncomplicated angina pectoris. However, angina patients who smoke have a greater
      risk of later infarction or death than do those who do not smoke. Most patients
      who suffer an infarction are moderate smokers. Non-smokers who suffer an
      infarction tend to be afflicted by more other risk factors than are smokers. The
      mechanism of infarction in smokers most often seems to be thrombosis in less
      atherosclerotic arteries. Stopping smoking is associated with lower mortality
      among patients after infarction and resuscitation from cardiac arrest. After
      coronary surgery re-infarction as well as new infarctions and angina pectoris are
      less common among patients who stop smoking than they are among those who
      continue to smoke. Factors such as an increase in body weight after stopping
      smoking are not associated with any increase in mortality among post-infarct
      patients. There are some psychosocial differences between those who stop smoking
      and those who continue to smoke after an infarction, but it is improbable that
      these differences explain the rapid effect on re-infarction and mortality rates
      of stopping smoking.

PMID- 10201553
TI  - Ispaghula husk in the treatment of hypercholesterolaemia: a double-blind
      controlled study.
AB  - BACKGROUND: Lowering cholesterol levels by natural dietary modification is an
      attractive first-line option for the treatment of mild-to-moderate
      hypercholesterolaemia. However, results have been less than impressive. The
      addition of soluble fibre - for example, psyllium or oat bran - to a modified
      diet has produced better results. In this study, the cholesterol-level-lowering
      effect of ispaghula husk and dietary advice was compared with placebo and dietary
      advice in treating patients with mild-to-moderate hypercholesterolaemia. METHODS:
      The double-blind, placebo-controlled, randomized comparison was conducted in 42
      general practices and three hospital centres in the UK. There was an initial 8
      week diet-only period and then a 1 2-week treatment period. Ispaghula treatment
      (7.0 or 10.5 g/day) was continued for a further 12 weeks for some patients. A
      total of 340 patients, aged 18 to 65, with mild-to-moderate hypercholesterolaemia
      [low-density lipoprotein (LDL) cholesterol levels of 4.1 mmol/l or more] entered
      the 12-week treatment phase. Levels of LDL cholesterol, total cholesterol, high
      density lipoprotein cholesterol, triglycerides and apolipoproteins A1 and B were
      determined. RESULTS: LDL cholesterol and total cholesterol levels fell during the
      diet-only period. In members of the intention-to-treat population after the 8
      week diet period, LDL cholesterol levels had fallen by 0.42 mmol/l (8.7%) for the
      7.0 g ispaghula/day group after 12 weeks of treatment, whereas LDL cholesterol
      levels had fallen by 0.48 mmol/l (9.7%) for the 10.5 g ispaghula/day group.
      Ispaghula at both doses produced significantly greater reductions in LDL
      cholesterol levels than did placebo (7.0 g/day versus placebo, P=0.009; 10.5
      g/day versus placebo, P<0.001). Ispaghula and modification of diet together
      reduced LDL cholesterol levels by 10.6-13.2% and total cholesterol levels by 7.7
      8.9% during the 6-month period. CONCLUSIONS: Ispaghula husk as an adjunct to diet
      is effective and well tolerated in the management of appropriate patients with
      mild-to-moderate primary hypercholesterolaemia.

PMID- 10201555
TI  - Is low serum chloride level a risk factor for cardiovascular mortality?
AB  - BACKGROUND: Serum chloride level is routinely assayed in clinical laboratories in
      the management of patients with kidney disorders and with metabolic diseases. It
      is a biological parameter that is easily, precisely and relatively cheaply
      measured. The epidemiological features of serum chloride levels have not been
      studied before. METHODS: For the random sample of men and women from the Belgian
      Interuniversity Research on Nutrition and Health aged 25-74 years, free of
      symptomatic coronary heart disease at baseline, serum chloride concentrations
      were measured, among those of other electrolytes. The cohort was followed up for
      10 years with respect to subsequent cause-specific mortality. RESULTS: The
      results are based on observations of 4793 men and 4313 women. According to Cox
      regression analysis serum chloride level was one of the strongest predictors of
      total, cardiovascular disease (CVD) and non-CVD mortalities independently of age,
      body mass index, sex, smoking, systolic blood pressure, levels of total and high
      density lipoprotein cholesterol, uric acid, serum creatinine and serum total
      proteins and intake of diuretics. This relation was proved to be independent of
      levels of other serum electrolytes and similar for men and women. The estimated
      adjusted risk ratio for CVD death for subjects with a serum chloride level < or
      =100 mmol/l compared with those with levels above that limit was 1.65 (95%
      confidence interval 1.06-2.57) for men and 2.16 (95% confidence interval 1.11
      4.22) for women. The study of adjusted risk ratios for four groups of subjects
      defined on the basis of their baseline serum chloride levels revealed a
      decreasing log-linear 'dose-response' relation to total and cardiovascular
      mortalities. CONCLUSION: This s the first report from a population-based study to
      indicate that there is an association between serum chloride level and the
      incidence of total, CVD and non-CVD mortalities. The risk ratio for CVD mortality
      associated with a low serum chloride level was comparable to or higher than those
      observed for well-established CVD risk factors.

PMID- 10201556
TI  - The psychological impact of screening for risk of coronary heart disease in
      primary care settings.
AB  - AIMS: A prospective study was conducted to identify the psychological impact of
      labelling middle-aged men as having above average risk for coronary heart
      disease. A second aim was to find out the psychological effect of participation
      in a subsequent clinical trial. METHODS: 5813 men attended nine special screening
      clinics in England and Scotland for baseline measurement of psychological
      symptoms and coronary disease risk factors. Each man was later informed of his
      risk status by letter as either above average risk (high-risk) or no special risk
      (low-risk). In three clinics some men also received an intermediate risk
      (moderate-risk) between high-risk and low-risk. Follow-up psychological
      measurements were made after labelling and 3 months later. RESULTS: Men who
      received either the high-risk label (n=838) or the low-risk label (n=3114) showed
      a decrease in reported psychological symptoms after labelling. Men receiving the
      unexpected intermediate risk (moderate-risk) label, which communicated specific
      test abnormalities, increased their psychological symptoms to 'case' levels on
      the General Health Questionnaire; relative risk (compared with low-risk) was 1.80
      (95% confidence interval 1.19-2.71) after adjustment for confounding factors.
      Compliers with a subsequent clinical trial decreased their risk of becoming cases
      and, if ill at trial entry, increased their case remission rate. CONCLUSIONS: The
      ascription of an 'above average risk' label for coronary disease to middle-aged
      men does not adversely affect the psychological state of those who receive it if
      they have received preparation for risk labelling. However, communicating
      abnormal coronary disease test results without adequate preparation confers short
      term psychological harm. Non-specific support from familiar general practice
      professionals received by participants in a clinical trial reduces the risk of
      psychological ill-health. All coronary disease screening programmes should
      include adequate pre-labelling preparation for all risk labels and abnormal
      results.

PMID- 10201557
TI  - Bibliography of current world literature.

PMID- 10201559
TI  - Passive alpha Electret Ion Chambers.

PMID- 10201558
TI  - Decommissioning of radiological facilities.

PMID- 10201560
TI  - A case study of selected medical findings among plutonium injectees.
AB  - Available medical records of plutonium injectees exposed in experimental studies
      of plutonium biokinetics under Manhattan Engineer District auspices have been
      reviewed for subsequent medical findings potentially related to the plutonium
      exposures. Five subjects who had been injected with approximately 11 kBq 239Pu,
      and one injected with 3.5 kBq 238Pu, had useful follow-up medical data. Bone
      lesions dominated the findings: none of six subjects with follow-up for bone
      conditions lacked bone lesions clearly or potentially caused, or worsened, by
      plutonium. Roentgenograms of three subjects, read by a radiologist experienced
      reading films of radium cases, demonstrated possible to likely plutonium effects.
      Two cases of osteoporosis or non-specific degenerative changes were seen,
      associated with a hip fracture and vertebral fractures. Areas of increased bone
      density were seen, as well as numerous dystopic calcifications and one unusual
      case of widespread pathologic calcification on bone surfaces probably due to a
      plutonium-related calciphylactic reaction. Non-skeletal findings include
      labyrinthitis with inflammatory mastoid changes, conduction deafness, and a
      benign neurofibroma directly adjacent to bone. The radium literature contains
      similar observed findings, but interpretation of these limited clinical
      observations is hampered by lack of quantitative data on humans exposed to radium
      with respect to prevalence of non-specific ear, mastoid, and skeletal
      symptomatologies or x-ray findings, or cumulative incidence rates of bone
      fractures or of other physical disabilities related to ear, mastoid, or bone
      damage. Disability and invalidism late in life can be risk factors for earlier
      mortality.

PMID- 10201561
TI  - Removal of strontium by the chelating agent acetylamino propylidene diphosphonic
      acid in rats.
AB  - Studies of the effects of the chelating agent, calcium acetylamino propylidene
      diphosphonic acid (Ca-APDA), on the removal of radioactive strontium with two
      administration modalities were carried out in rats. The parenteral
      (intraperitoneal) administration of 150, 300, or 600 mg kg(-1) Ca-APDA was
      carried out for 3 d, 10 min after exposure of the animals to the strontium
      injection. On the first day post-treatment, the retention of strontium in the
      whole body decreased to 90.1%, 83.9%, and 35.1% that of the control level,
      respectively. The strontium deposited in femur of 600 mg kg(-1) Ca-APDA group was
      lowered to 28.4% of the control value. A single oral dose of 600 mg kg(-1) Ca
      APDA administered simultaneously with, or 10 min after, oral administration of
      strontium, radionuclide retention in the whole body was reduced after 1 d to
      42.9% and 31.9% of the control, respectively; meanwhile the strontium deposited
      in the femur was reduced to 16.9% and 29.3% of the control. In conclusion, the
      results indicate the efficacy of the new agent, Ca-APDA, to remove radioactive
      strontium from the body, or to inhibit the strontium intestinal absorption, in
      radio-strontium contaminated individuals.

PMID- 10201562
TI  - Dynamic modeling of the cesium, strontium and ruthenium transfer to grass and
      vegetables.
AB  - From 1988 to 1993, the Nuclear Safety and Protection Institute (Institut de
      Protection et de Surete Nucleaire--IPSN) conducted experimental programs focused
      on transfers to vegetation following accidental localized deposits of radioactive
      aerosols. In relation to vegetable crops (fruit, leaves, and root vegetables) and
      meadow grass these experiments have enabled a determination of the factors
      involved in the transfer of cesium, strontium, and ruthenium at successive
      harvests, or cuttings, in respect of various time lags after contamination. The
      dynamic modeling given by these results allows an evaluation of changes in the
      mass activity of vegetables and grass during the months following deposit. It
      constitutes part of the ASTRAL post-accident radioecology model.

PMID- 10201563
TI  - Comparative study of the PARK and ASTRAL post-accidental decision support
      software.
AB  - The French radioecological assessment model ASTRAL and the German model PARK have
      been developed to evaluate the radiological situation in the case of an
      accidental release of radionuclides and a widespread contamination of the
      environment. For decision makers it is of importance that the results on
      foodstuff contamination and on dose to humans are in fairly good agreement, when
      areas of the common border are affected. Therefore a comparative study has been
      done for two scenarios, assuming accidental releases on 1 June and 1 October. The
      study indicates that the models' structures and the transfer parameters are in
      good agreement. Only model principles for root vegetables are different in both
      models. Significant differences in results on the contamination of foodstuff and
      on dose to humans by ingestion are caused by different assumptions on dates of
      harvest and feeding methods of animals. A corresponding harmonization is
      essential with respect to decision making.

PMID- 10201564
TI  - Implication of microdosimetry in estimation of radiation quality in space
      environment.
AB  - Errors introduced using a tissue equivalent proportional counter to estimate
      radiation quality of an arbitrary ion field as related to space radiations are
      examined. This is accomplished by using a generalized analytic model to calculate
      the effect of energy loss straggling, track structure, and pathlength
      distribution on the microdosimetric distribution. The error can be as large as a
      factor of two, but no systematic trend could be found.

PMID- 10201565
TI  - Spatial variations in natural background radiation: absorbed dose rates in air in
      Colorado.
AB  - Large and small-scale spatial variations in natural ambient background radiation
      dose rates in Colorado were investigated at 1,150 specific locations with
      particular attention to 40 of the more populated areas along the Front Range of
      the Rocky Mountains. Total dose rates (including cosmic and terrestrial
      components) in Front Range communities below 2,000 m elevation averaged 135 nGy
      h(-1). Terrestrial dose rates had a coefficient of variation of 17%. Communities
      above 2,000 m had a mean total dose rate of 196 nGy h(-1), and a terrestrial dose
      rate coefficient of variation of 17%. Across all Front Range communities, the
      coefficient of variation for terrestrial dose rates was 22%. Within individual
      communities, coefficient of variation values for terrestrial dose rates ranged
      from 3 to 21%. Smaller-scale spatial variability (to within a few meters) was
      relatively small (coefficient of variation values generally ranged from 3 to 7%).
      A significant linear relationship (r2 = 0.83) between the size of area surveyed
      (km2) and coefficient of variation value for terrestrial dose rates was found.
      West of the Continental Divide, the terrestrial component accounted for roughly
      60% of total measured dose rates, while east of the Continental Divide, where
      enriched granitic source rocks and associated soils are prevalent, the
      terrestrial component generally accounted for two-thirds or more of total dose
      rates.

PMID- 10201566
TI  - Prediction of in vivo background in phoswich lung count spectra.
AB  - Phoswich scintillation counters are used to detect actinides deposited in the
      lungs. The resulting spectra, however, contain Compton background from the decay
      of 40K, which occurs naturally in the striated muscle tissue of the body. To
      determine the counts due to actinides in a lung count spectrum, the counts due to
      40K scatter must first be subtracted out. The 40K background in the phoswich
      NaI(TI) spectrum was predicted from an energy region of interest called the
      monitor region (95-129 keV), which is above the 238Pu region (11-32 keV) and the
      241Am region (40-82 keV), where photopeaks from 238Pu and 241Am occur. Empirical
      models were developed to predict the backgrounds in the 238Pu and 241Am regions
      by testing multiple linear and nonlinear regression models. The initial multiple
      regression models contain a monitor region variable as well as the variables
      gender, (weight/height)alpha, and interaction terms. Data were collected from 64
      male and 63 female subjects with no internal exposure. For the 238Pu region, the
      only significant predictor was found to be the monitor region. For the 241Am
      region, the monitor region was found to have the greatest effect on prediction,
      while gender was significant only when weight/height was included in a model.
      Gender-specific models were thus developed. The empirical models for the 241Am
      region that contain weight/height were shown to have the best coefficients of
      determination (R2) and the lowest mean squares for error (MSE).

PMID- 10201567
TI  - Radon progeny unattached fraction in an atmosphere far from radioactive
      equilibrium.
AB  - It is often assumed that the unattached fraction of the exposure to suspended
      radon progeny activity can be predicted from particle concentration measurements.
      While this may be true in many circumstances, there are important exceptions to
      this rule. In particular, in an atmosphere far from radioactive equilibrium, such
      as a working area in a mine close to a source of radon and supplied with fresh
      air, the unattached fraction can be a factor of ten or more greater than
      indicated by a simple particle concentration measurement. Recent measurements
      made in a diesel powered uranium mine are presented to illustrate this effect.

PMID- 10201568
TI  - Radon action level for high-rise buildings.
AB  - Radon and its progeny are the major contributors to the natural radiation dose
      received by human beings. Many countries and radiological authorities have
      recommended radon action levels to limit the indoor radon concentrations and,
      hence, the annual doses to the general public. Since the sources of indoor radon
      and the methods for reducing its concentration are different for different types
      of buildings, social and economic factors have to be considered when setting the
      action level. But so far no action levels are specifically recommended for cities
      that have dwellings and offices all housed in high-rise buildings. In this study,
      an optimization approach was used to determine an action level for high-rise
      buildings based on data obtained through previous territory-wide radon surveys. A
      protection cost of HK$0.044 per unit fresh air change rate per unit volume and a
      detriment cost of HK$120,000 per person-Sv were used, which gave a minimum total
      cost at an action level of 200 Bq m(-3). The optimization analyses were repeated
      for different simulated radon distributions and living environment, which
      resulted in quite significantly different action levels. Finally, an action level
      of 200 Bq m(-3) was recommended for existing buildings and 150 Bq m(-3) for newly
      built buildings.

PMID- 10201569
TI  - Calculation of the number of cancer deaths prevented by the Uranium Mill Tailings
      Remedial Action Project.
AB  - The Uranium Mill Tailings Remedial Action Project has completed remedial action
      at 22 uranium mill tailings sites and about 5,000 properties ("vicinity
      properties") where tailings were used in construction, at a total cost of $1.45
      billion. This paper uses existing data from Environmental Impact Statements and
      Environmental Assessments, and vicinity property calculations, to determine the
      total number of cancer deaths averted by the Uranium Mill Tailings Remedial
      Action Project. The cost-effectiveness of remediating each site, the vicinity
      properties, and the entire project is calculated. The cost per cancer death
      averted was four orders of magnitude higher at the least cost-effective site than
      at the most cost-effective site.

PMID- 10201570
TI  - Comparison of sliced and whole lung sets for the LLNL and JAERI torso phantoms
      using GE detectors.
AB  - The performance characteristics of sliced lung sets were compared to lung sets
      with activity homogeneously distributed throughout the lung tissue substitute
      material. The activity estimate from planar sources differs from the estimate
      from homogeneous sources by a factor of 0.88 to 1.09 depending on the photon
      energy. This error is small compared to other uncertainties commonly encountered
      in lung counting, i.e., activity deposition in the lung, detector placement, size
      difference between individuals, etc. Sliced lung sets could be used instead of
      homogeneous lung sets to test or provide an interim calibration for a lung
      counting system.

PMID- 10201571
TI  - The residential radon-lung cancer association in U.S. counties: a commentary.
AB  - There is little doubt that underground miners exposed to radon and its progeny
      have increased rates of lung cancer. Residential radon exposures should carry a
      possibly smaller risk of increased cancer. When it became possible to collect
      radon data in a large number of U.S. homes and the data were aggregated by
      counties, the apparent association with lung cancer was a negative one, even when
      many other variables were taken into account. Residential radon levels are higher
      in suburban residences leading to a negative association with population density.
      Population density is strongly positively associated with lung cancer. It follows
      that aggregate residential radon and lung cancer rates should be negatively
      associated for reasons having nothing to do with the possibility of radon being
      carcinogenic to the lung. A second problem presented by the data is the one of
      sampling bias since the county lung cancer data are from the whole county
      population, but only a few residences are tested. Examples of other inherent
      associations in environmental epidemiology are cited. One strategy is to study
      areas of the same population density but with radon exposure gradients. This is
      approximated by choice of rural high radon states. Counties in such states have
      weak and inconsistent associations between radon and lung cancer, some of which
      are positive. I conclude that counties are generally inappropriate units for
      study of radon and lung cancer associations.

PMID- 10201573
TI  - Effective dose equivalent due to gamma-ray emissions from hot particles.
AB  - The quantification of dose from hot particles in the nuclear power industry has
      received a good deal of attention in the past few years. Specifically,
      calculational models have been developed to determine shallow dose equivalent
      from both beta and gamma-rays (using VARSKIN) and to estimate deep dose
      equivalent based upon the gamma dose at a tissue depth of 1 cm. These two values
      are reported for regulatory purposes. The purpose of this study is to estimate
      another measure of dose from hot particles (or from skin contamination over a
      small area), specifically the effective dose equivalent which takes into account
      all organs of the body receiving appreciable dose from the gamma-ray emissions
      from the contamination. While it is generally recognized that this dose will be
      small, this study gives representative doses for a range of hot particle
      locations and gamma-ray energies. MCNP and the ADAM phantom have been used for
      the calculational model. The effective dose equivalent is found to range from 0.1
      to 12 microSv h(-1) MBq(-1) (0.4 to 43 microrems h(-1) microCi(-1)) of gamma
      activity, depending upon the location of the hot particle on the body.

PMID- 10201572
TI  - Intercomparison of passive radon-detectors under field conditions in
      epidemiological studies.
AB  - The Ardennes and Eifel region is a geologically distinct area covering parts of
      Germany, Belgium, France, and Luxembourg where enhanced concentrations of radon
      occur in some houses and other buildings. An international case-control study is
      being conducted to examine the role of radon in the etiology of lung cancer in
      this area. The radon detectors used are issued by different laboratories
      involving a variety of detector types and processes. A series of intercomparisons
      in houses was therefore conducted under similar conditions of exposure in the
      field. In most situations the different detectors gave similar results.
      Nevertheless, in some situations open and closed detectors yielded different
      results. Therefore, estimates of radon exposure have to be adjusted if results
      are to be pooled.

PMID- 10201574
TI  - Excessive safety factor in 1998 ICNIRP guidelines reflects lack of participation
      of all stakeholders in the ICNIRP process.

PMID- 10201575
TI  - Response to the Goldsmith commentary.

PMID- 10201576
TI  - Primary intraocular lens implantation for lens trauma.

PMID- 10201577
TI  - Cyclophotocoagulation for glaucoma after penetrating keratoplasty.

PMID- 10201578
TI  - Prevalence of retinal detachments in children with chorioretinal colobomas.

PMID- 10201579
TI  - Aspirin and cataract risk.

PMID- 10201580
TI  - Choroidal neovascularization and age-related macular degeneration.

PMID- 10201581
TI  - External dacryocystorhinostomy versus endonasal laser dacryocystorhinostomy.

PMID- 10201582
TI  - Anterior ischemic optic neuropathy: trouble waiting to happen.

PMID- 10201583
TI  - The Collaborative Initial Glaucoma Treatment Study: study design, methods, and
      baseline characteristics of enrolled patients.
AB  - OBJECTIVE: The Collaborative Initial Glaucoma Treatment Study (CIGTS) is a
      randomized, controlled clinical trial designed to determine whether patients with
      newly diagnosed open-angle glaucoma (primary, pigmentary, or pseudoexfoliative)
      are better treated by initial treatment with medications or by immediate
      filtration surgery. DESIGN: Randomized, controlled clinical trial. PARTICIPANTS:
      A total of 607 patients with open-angle glaucoma were enrolled. INTERVENTION:
      Patients randomized to initial medications (n=307) received a stepped regimen of
      medications to lower intraocular pressure. Those randomized to initial surgery
      (n=300) underwent trabeculectomy to lower intraocular pressure. MAIN OUTCOME
      MEASURES: Progression in visual field loss constitutes the study's primary
      outcome variable. Secondary outcomes include health-related quality of life,
      visual acuity, and intraocular pressure. RESULTS: Randomized assignment resulted
      in a balanced distribution between treatment groups for most demographic and
      clinical measures assessed at enrollment. More males than females were enrolled
      (55% were males), and a substantial percentage (38.1 %) of enrollees were blacks.
      Most enrollees (90.6%) were diagnosed with primary open-angle glaucoma; the
      remainder had either pseudoexfoliative (4.8%) or pigmentary (4.6%) forms of open
      angle glaucoma. CONCLUSIONS: Follow-up of this well-characterized group of
      patients should provide well-rounded guidance, based on both traditional
      ophthalmic measures and patients' perspectives on their health-related quality of
      life, on how best to initially treat open-angle glaucoma.

PMID- 10201584
TI  - The natural history of macular edema after cataract surgery in diabetes.
AB  - OBJECTIVE: To determine the natural history of macular edema after cataract
      surgery in diabetes to provide a rational basis for laser therapy. DESIGN:
      Prospective clinical and angiographic trial. PARTICIPANTS: Thirty-two patients
      with diabetes undergoing cataract surgery. INTERVENTION: Phacoemulsification
      surgery with intraoperative fluorescein angiography, and postoperative clinical
      and angiographic assessment without macular laser therapy for 1 year after
      surgery. MAIN OUTCOME MEASURES: Clinically significant macular edema,
      postoperative macular and optic disc hyperfluorescence relative to the
      intraoperative angiogram, and logarithm of the minimum angle of resolution
      (LogMAR) visual acuity. RESULTS: In the first postoperative year, macular
      fluorescence remained at its intraoperative level in 2 (6%) of 32 eyes and
      increased in 30 (94%) of 32 eyes, returning to its intraoperative level within 1
      year of surgery in 13 (43%) of 30 eyes. Optic disc fluorescence remained at its
      intraoperative level in 2 (6%) of 32 eyes, was not graded in 3 (9%) of 32 eyes,
      and increased in 27 (84%) of 32 eyes, returning to its intraoperative level
      within 1 year of surgery in 19 (70%) of 27 eyes. Clinically significant macular
      edema was identified in the first postoperative year in 18 (56%) of 32 eyes,
      being present at the time of surgery in 5 eyes and arising de novo within 1 year
      of surgery in 13 eyes. It resolved spontaneously within 1 year of surgery in 0 of
      5 eyes in which it had been present at the time of surgery and in 9 (69%) of 13
      eyes in which it arose in the first 6 months after surgery (P = 0.05).
      Angiographic and clinical resolutions of macular edema were less likely in eyes
      with more severe retinopathy at the time of surgery (P = 0.03, 0.005). One-year
      LogMAR acuity of 0.3 or less (> or = 20/40) was achieved in 27 (84%) of 32 eyes.
      Clinically significant macular edema at the time of surgery was associated with
      poorer 1-year visual acuity in multivariate analysis (P = 0.005, r2 = 0.5).
      CONCLUSIONS: Clinically significant macular edema present in diabetic eyes at the
      time of cataract surgery is unlikely to resolve spontaneously, but clinically
      significant macular edema arising after surgery commonly resolves, particularly
      if retinopathy is mild. These findings have implications for the timing of
      cataract surgery in diabetes and postoperative macular laser therapy.
      Ophthalmology 1999;106:663-668

PMID- 10201585
TI  - Combined phacoemulsification and goniosynechialysis for uncontrolled chronic
      angle-closure glaucoma after acute angle-closure glaucoma.
AB  - OBJECTIVE: To evaluate combined phacoemulsification, posterior chamber
      intraocular lens (PCIOL) implantation, and goniosynechialysis (phaco-GSL)
      prospectively in eyes with more than 180 degrees of peripheral anterior synechiae
      (PAS) and uncontrolled intraocular pressure (IOP) when performed within 6 months
      of an attack of acute angle-closure glaucoma (ACG). DESIGN: Prospective,
      noncontrolled clinical trial. PARTICIPANTS: Patients who had presented with acute
      ACG and had persistently uncontrolled IOP despite successful laser iridotomy for
      pupillary block and argon laser peripheral iridoplasty for continued appositional
      closure after iridotomy. INTERVENTION: After the completion of
      phacoemulsification and posterior chamber lens implantation, goniosynechialysis
      was performed in 52 eyes of 48 patients. MAIN OUTCOME MEASURES: Postoperative
      visual acuity, IOP, extent of PAS, and number of medications, if any, required
      for IOP control. RESULTS: Intraocular pressure was less than 20 mmHg in 47 eyes
      (90.4%) without medications; 4 were controlled with medications and 1 required
      filtration. Mean extent of PAS was reduced from 310 degrees to 60 degrees.
      Peripheral anterior synechiae formation or IOP elevation did not recur after 3
      months after surgery up to 6 years. Eight patients achieved 20/20 visual acuity,
      while 44 patients had less than 20/20 visual acuity. No patient had worse visual
      acuity after surgery compared to before surgery. CONCLUSION: Phaco-GSL and PCIOL
      implantation is effective in reducing PAS and IOP and improving visual acuity in
      eyes with persistent chronic ACG when performed within 6 months after treatment
      for acute ACG.

PMID- 10201586
TI  - Comparison of the results of first and second cataract eye surgery.
AB  - OBJECTIVE: To compare the outcomes of second eye cataract surgery with those of
      first eye surgery. In particular, to evaluate changes in visual acuity (VA),
      visual function, and health status after the first and second eye surgeries.
      DESIGN: A cohort (case series) analysis of patients recruited in a clinical
      trial. PARTICIPANTS: A total of 403 consecutive patients with indication of
      noncombined first eye or second eye cataract surgery were recruited in 3 public
      hospitals in Barcelona, Spain. First eye surgery patients are compared to second
      eye surgery patients. INTERVENTION: Patients were evaluated both before surgery
      and 4 months after surgery by a standardized telephone interview and clinical
      examination. MAIN OUTCOME MEASURES: Visual acuity, visual function index (VF-14),
      a 14-item instrument designed to measure visual function, and the Sickness Impact
      Profile (SIP), a generic measure of health status. RESULTS: Full data were
      obtained from 315 (78%) patients: 249 who underwent first eye surgery only and 66
      different patients who underwent second eye surgery. Significant improvement was
      found in both groups of patients for best-corrected VA in the operated eye (4.4
      Snellen lines, P < 0.001; 4.2 Snellen lines, P < 0.001, respectively), VA in the
      better eye (2.8 Snellen lines, P < 0.001; 1.4 Snellen lines, P < 0.001), and
      visual function (26.3 Snellen lines, P < 0.001; 17.0 Snellen lines; P < 0.001).
      Four months after the operation, the VF-14 of the second eye group was slightly
      better (93.4 vs. 88.5; P = 0.09; score range: 0, worst, to 100, best). Psycho
      social SIP scores improved in both groups (4.8, P < 0.001; 3.1, P = 0.016).
      Physical SIP score improved only in the first eye surgery group (1.8, P = 0.003)
      but not in the second eye surgery group (-1.0, P = 0.338; score range: 0, best,
      to 100, worst). CONCLUSIONS: The results of our study suggest that patients
      undergoing second eye cataract surgery show significant improvements in VA,
      visual function, and psycho-social health status. However, global and physical
      health status does not change after second eye cataract surgery.

PMID- 10201587
TI  - Schizophrenia, psychotropic medication, and cataract.
AB  - OBJECTIVE: To compare the distribution of cataract types between psychiatric
      patients diagnosed with schizophrenia and the general population not exposed to
      psychotropic medication, and to compare cataract prevalence between users and
      nonusers of various psychotropic medications in the general community. DESIGN:
      Case-control. PARTICIPANTS: A total of 151 (93%) eligible patients from a
      community mental health service and 3271 (83%) eligible residents from the
      Melbourne Visual Impairment Project (VIP) were examined. MAIN OUTCOME MEASURES:
      All patients 40 years of age and older from a community mental health service and
      residents of nine randomly selected areas of Melbourne were eligible. Best
      corrected distance visual acuity was determined using a 4-m logarithm of the
      minimum angle of resolution (LogMAR) chart. The presence of cataract was
      determined by photographs or slit-lamp examination using direct and indirect
      retroillumination. Anterior, cortical, nuclear, and posterior subcapsular
      cataracts were measured. Participants from the Melbourne VIP were classified as
      to whether they had taken benzodiazepams, phenothiazines, thioxanthenes,
      butyrophenols, tricyclic antidepressants, or monoamine oxidase inhibitors for at
      least 12 months during their lifetime. RESULTS: The distribution of cataract type
      varied between persons with and without schizophrenia. Anterior subcapsular (ASC)
      cataract was significantly more prevalent (26%) in participants with
      schizophrenia from the community mental health service than Melbourne VIP
      participants (0.2%) not exposed to psychotropic medication (chi-square, 1 degree
      of freedom = 605.5, P = 0.001). This remained significant after controlling for
      age (odds ratios = 250, 95% confidence interval = 83.3, 1000). The distribution
      of the age-related cataract was similar across all groups of psychotropic
      medication users with the exception of the phenothiazine users. They had less of
      all types of the age-related cataracts, despite being slightly older than the
      control group (mean age, 60.0 vs. 58.4, t test = 0.85, P = 0.40). However, only
      cortical cataract in the phenothiazine group was statistically lower (chi-square,
      1 degree of freedom = 3.96, P = 0.047). CONCLUSION: This study has identified the
      need to investigate whether other newer agents, especially high-potency
      medications, cause ASC opacities if a certain threshold of exposure to
      psychotropic medications must be attained to develop cataract, or if
      schizophrenia itself is associated with cataract formation.

PMID- 10201588
TI  - Retinal complications after cataract extraction in patients with high myopia.
AB  - OBJECTIVE: To assess risk factors and incidence of retinal complications after
      cataract extraction in patients with high myopia. DESIGN: Retrospective,
      noncomparative case series. PARTICIPANTS: One hundred eighteen patients with
      highly myopic eyes who had an axial length of 26 mm or more (mean axial length,
      30.13 +/- 2.08 mm) and who underwent cataract surgery over a period of 6 years
      were studied. INTERVENTION: Patients underwent cataract extraction either by
      extracapsular cataract extraction (ECCE) or phacoemulsification. Prophylactic
      argon laser photocoagulation was performed in 13 eyes for retinal tears
      recognized before surgery and in 13 eyes after surgery; neodymium:YAG (Nd:YAG)
      laser capsulotomy was performed for patients with posterior capsule opacification
      (PCO) that affected the vision. MAIN OUTCOME MEASURES: Incidence of retinal
      detachment and PCO and percentage of prophylactic argon laser or of Nd:YAG laser
      treatments. RESULTS: Of the 118 eyes, 73 (61.9%) underwent ECCE and 45 (38.1%)
      underwent phacoemulsification. Posterior capsule opacification was the most
      common complication and was found in 30 eyes (25.4%). Thirteen patients (11%)
      received prophylactic laser treatment for retinal tears before cataract
      operation, and 13 more patients (11%) had postoperative retinal tears requiring
      laser treatments. None of these patients developed retinal detachment. Two
      patients (1.69%) developed retinal detachment within 6 months after their
      operations. There were no intraoperative complications, and postoperative Nd:YAG
      capsulotomy was not performed in these two patients. CONCLUSIONS: Active
      searching and prophylactic laser treatments for retinal tears developed before
      and after cataract extraction in patients with high myopia are recommended. This
      may lower the incidence of postoperative retinal detachment.

PMID- 10201590
TI  - The effect of neodymium: YAG capsulotomy on contrast sensitivity and the
      evaluation of methods for its assessment.
AB  - OBJECTIVE: To determine the most appropriate method for measuring the effect on
      contrast sensitivity of neodymium:YAG (Nd:YAG) posterior capsulotomy for early
      posterior capsular opacification (PCO). DESIGN: Prospective comparison of five
      different methods for luminous contrast sensitivity testing in patients
      undergoing capsulotomy. PARTICIPANTS: Sixteen patients with PCO involving the
      visual axis and visual acuities of 20/40 or better were recruited sequentially.
      INTERVENTION: All patients were tested with each of the five tests before and
      after Nd:YAG capsulotomy. MAIN OUTCOME MEASURES: The contrast sensitivity
      function was measured with variable contrast sine wave gratings using the Vistech
      VCTS 6500, Mentor B-VAT-II and a computer graphics system. Peak contrast
      sensitivity at 3 cyc/deg was compared with two letter tests, the Pelli-Robson
      chart, and a computer that generated optotypes. RESULTS: Significant generalized
      improvement that was not frequency selective was measured over the entire
      contrast sensitivity function after capsulotomy. The five tests did not
      significantly differ (P > 0.05) in their measurement of peak contrast sensitivity
      (3 cyc/deg) improvement after capsulotomy. Letter-based tests showed better
      agreement and lower variance than gratings tests. Visual acuity and contrast
      sensitivity improvement were poorly correlated. CONCLUSIONS: This study shows
      that contrast sensitivity is adequately documented by a single measurement at 3
      cyc/deg, is an informative supplement to visual acuity, and that little extra
      information is to be gained by measuring further spatial frequencies in eyes with
      PCO. Peak contrast sensitivity is best determined using a letter-based test.

PMID- 10201589
TI  - Underestimation of intraocular lens power for cataract surgery after myopic
      photorefractive keratectomy.
AB  - OBJECTIVE: To assess the validity of corneal power measurement and standard
      intraocular lens power (IOLP) calculation after photorefractive keratectomy
      (PRK). DESIGN: Nonrandomized, prospective, cross-sectional, clinical study.
      PARTICIPANTS: A total of 31 eyes of 21 females and 10 males with a mean age at
      the time of surgery of 32.3 +/- 6.6 years (range, 24.4-49.5 years). INTERVENTION:
      Subjective refractometry, standard keratometry, TMS-1 corneal topography
      analysis, and pachymetry were performed before and 15.8 +/- 10.4 months after PRK
      for myopia (n = 24, -1 .5 to -8.0 diopters [D], mean -5.4 +/- 1.9 D) or myopic
      astigmatism (n = 7, sphere -2.0 to -7.5 D, mean -4.4 +/- 1.9 D; cylinder -1.0 to 
      3.0 D, mean -1.9 +/- 0.7 D). The IOLP calculations were done using two different
      formulas (SRK/T and HAIGIS). MAIN OUTCOME MEASURES: Keratometric power (K) and
      topographic simulated keratometric power (TOPO) as measured (Kmeas, TOPOmeas) and
      as calculated according to the change of power of the anterior corneal surface or
      according to the spherical equivalent change after PRK (Kcalc, TOPOcalc), IOLP
      for emmetropia, and postoperative ametropia for calculated corneal powers were
      assessed in a model. RESULTS: After PRK, mean Kmeas and TOPOmeas were
      significantly greater (0.4-1.4 D, maximum 3.3 D) than mean KRcalc and TOPOcalc (P
      < 0.0001). On average, the relative flattening of the cornea after PRK was
      underestimated by 14% to 30% (maximum, 83%) depending on the method of
      calculation. The mean theoretical IOLP after PRK ranged from + 17.4 D (SRK/T,
      TOPOmeas) to +20.9 D (HAIGIS, Kcalc) depending on the calculation method for
      corneal power and IOLP calculation formula used. For both formulas, IOLP values
      using keratometric readings were significantly higher (>1 D) than IOLP values
      using topographic readings (P < 0.0001). The theoretically induced mean
      refractive error after cataract surgery ranged from +0.4 to +1.4 (maximum, +3.1)
      D. Corneal power overestimation and IOLP underestimation correlated significantly
      with the spherical equivalent change after PRK (P = 0.001) and the intended
      ablation depth during PRK (P = 0.004). CONCLUSIONS: To avoid underestimation of
      IOLP and hyperopia after cataract surgery following PRK, measured corneal power
      values must be corrected. The calculation method using spherical equivalent
      change of refraction at the corneal plane seems to be the most appropriate
      method. In comparison with this method, direct power measurements underestimate
      corneal flattening after PRK by 24% on average. Use of conventional topography
      analysis seems to increase the risk of error. However, because this study is
      retrospective and theoretical, there is still a need for a large prospective
      investigation to validate the authors' findings.

PMID- 10201591
TI  - Assessment of visual outcome after cataract surgery in patients with uveitis.
AB  - OBJECTIVE: To assess the outcome of cataract surgery in eyes of patients with
      uveitis. DESIGN: Prospective, noncomparative case series. PARTICIPANTS: A total
      of 90 eyes of 76 patients fulfilled the enrollment criteria. INTERVENTION: All
      patients had their surgery performed using standard cataract extraction
      techniques. Unless contraindicated, preoperative systemic steroids were
      administered to all patients with posterior disease, chronic anterior uveitis,
      with known macular edema, and those in whom outcome of cataract surgery on the
      fellow eye had been poor. RESULTS: Patients were divided into those with anterior
      disease (n = 53) and those with posterior disease (n = 37). Overall, 81 (90%) of
      90 eyes showed improvement in vision (median +4 Snellen lines). In those with
      anterior disease, the development of severe uveitis in the first week postsurgery
      was associated with a greater incidence of macular edema (P = 0.014). The single
      largest diagnosis in those with posterior disease was that of panuveitis (n =
      24). This group showed the poorest visual outcomes in this study. The majority of
      patients, however, were noted to have visual loss secondary to conditions present
      before surgery. CONCLUSION: Cataract surgery in eyes with uveitis leads to an
      improvement of vision in the majority of cases. Severe postoperative uveitis is
      the most common postoperative complication and is associated with a significant
      risk of macular edema in those with anterior disease. In the posterior group,
      poor visual outcome after surgery is most commonly the result of preoperative
      vision-limiting conditions.

PMID- 10201592
TI  - Tacrolimus (FK506) in the treatment of posterior uveitis refractory to
      cyclosporine.
AB  - OBJECTIVE: To assess the efficacy and side effects of tacrolimus, a potent
      immunosuppressive macrolide antibiotic, in the treatment of sight-threatening
      uveitis. DESIGN: A clinical study of tacrolimus in patients who required systemic
      immunosuppression for control of uveitis, but were refractory to cyclosporine.
      PARTICIPANTS: Six patients with uveitis were treated: three had Behcet disease,
      one had microscopic polyangiitis, one had pars planitis, and one had idiopathic
      retinal vasculitis. INTERVENTION: Patients with sight-threatening uveitis
      refractory to cyclosporine were treated with tacrolimus. MAIN OUTCOME MEASURES:
      Intraocular inflammation, visual acuity (VA), neovascularization. Adverse effects
      of tacrolimus were documented. RESULTS: The posterior uveitis remained controlled
      in all patients while they were taking tacrolimus. Five of the six patients
      showed improvement, defined as improvement of two or more lines of Snellen acuity
      or a decrease in the binocular indirect ophthalmoscopy score (P < 0.05, Sign
      test). One patient with Behcet disease showed a marked improvement in best
      corrected VA from 1/60 to 6/24. Two patients with Behcet disease showed a modest
      improvement in VA in the affected eye and had no disease activity in the other
      eye. The patient with microscopic polyangiitis was symptomatically improved, and
      there was no progression of the posterior uveitis. The patient with pars planitis
      had an improvement in VA from 6/18 to 6/9. The patient with retinal vasculitis
      showed partial regression of neovascularization on tacrolimus. Side effects were
      less troublesome than with cyclosporine. CONCLUSIONS: Tacrolimus (FK506) has a
      useful role as an immunosuppressive agent for the treatment of sight-threatening
      uveitis in patients who did not respond to cyclosporine either because of lack of
      therapeutic effect or unacceptable adverse effects.

PMID- 10201593
TI  - Severity of episcleritis and systemic disease association.
AB  - OBJECTIVE: To analyze patient characteristics and correlate between the site and
      severity of the inflammation and ocular and/or systemic disease association in a
      cohort of patients with episcleritis. DESIGN: Retrospective case series. METHODS:
      Medical records of 100 patients with episcleritis were reviewed. Data were
      analyzed using a customized database software. RESULTS: The age range at
      presentation was 18 to 76 years (mean, 43; median, 44). Sixty-nine percent of the
      patients were female. Thirty-two (32%) patients had bilateral involvement. The
      episcleritis was nodular in 23 eyes (16%). Half of the patients had a concurrent
      eye disease. Associated systemic disease was found in 36 patients (36%). In two
      patients, episcleritis preceded a systemic vasculitic disease (Wegener
      granulomatosis and Cogan syndrome). Ocular complications included uveitis
      (11.4%), corneal involvement (15%), and glaucoma (7.8%). No significant
      correlation of the site and severity of inflammation to the presence of
      associated systemic or ocular diseases was found. The mean follow-up was 16.5
      months. Twenty-eight patients experienced recurrence of episcleritis during the
      follow-up. Half of the patients required treatment with oral nonsteroidal anti
      inflammatory drugs. CONCLUSIONS: Episcleritis is usually a benign, self-limited
      disease, but it should not be trivialized since it may be associated with
      systemic disease and ocular complications. A careful review of systems should be
      performed in all patients presenting with episcleritis, and this should be
      repeated at least annually during the follow-up. A thorough eye examination is
      obviously essential to detect and treat ocular complications.

PMID- 10201594
TI  - Prospective randomized comparison of simultaneous and sequential bilateral laser
      in situ keratomileusis for the correction of myopia.
AB  - OBJECTIVE: To study the safety and efficacy of simultaneous bilateral laser in
      situ keratomileusis (LASIK). DESIGN: Prospective randomized clinical trial.
      PARTICIPANTS: Fourteen surgeons and 714 consecutive eyes of 357 patients who
      desired surgical correction of myopia ranging from -2.00 to -22.50 diopters.
      INTERVENTION: Patients were randomized to simultaneous or sequential bilateral
      LASIK. MAIN OUTCOME MEASURES: Primary outcome measures were safety and efficacy.
      Procedure safety was assessed, for simultaneous and sequential groups, by
      comparison of intraoperative and postoperative complication rates and the
      percentage of eyes losing two or more lines of spectacle-corrected visual acuity.
      Procedure efficacy was assessed by comparison of the percentage of eyes with
      uncorrected visual acuity better than or equal to 20/20 and 20/40 and the
      percentage of eyes within +/-0.50 and +/-1.00 diopters of intended outcome.
      RESULTS: Three hundred seventy-eight eyes were enrolled in the simultaneous
      group, and 331 eyes were enrolled in the sequential group. Mean follow-up was 10
      months (+/-4.2 months standard deviation; range, 2 weeks-22 months). There was no
      significant difference in intraoperative complication rate (P = 0.55), loss of
      two or more lines of spectacle-corrected visual acuity (P = 0.87), or percentage
      of eyes within +/-0.50 diopters of intended correction (P = 0.17) between
      simultaneous and sequential groups. Postoperative complications were not
      significantly different in the two groups except for the unexplained more
      frequent epithelial ingrowth in the simultaneous group (2.9%) than in the
      sequential group (0.6%). The adjusted odds ratio for epithelial ingrowth in the
      simultaneous group was 1.02 (95% confidence interval, 1.01-1.08). There was no
      increased likelihood of epithelial ingrowth in the second of two simultaneously
      treated eyes (P = 0.95). CONCLUSION: The outcomes and complications of performing
      bilateral simultaneous LASIK were not significantly different from those of
      sequential treatments, with the unexplained exception of more frequent epithelial
      ingrowth in the simultaneous group.

PMID- 10201595
TI  - Analysis of prothrombotic and vascular risk factors in patients with nonarteritic
      anterior ischemic optic neuropathy.
AB  - OBJECTIVE: To determine whether genetic or acquired thrombophilias and other risk
      factors are associated with nonarteritic anterior ischemic optic neuropathy
      (NAION). DESIGN: Retrospective case-control study. PARTICIPANTS: Sixty-one
      patients with NAION diagnosed between 1984 and 1997. Ninety consecutive patients
      who visited the Eye Institute made up the control group. INTERVENTION: Protein C,
      protein S, antithrombin III, lupus anticoagulant, and three recently described
      prothrombotic polymorphisms (i.e., factor V G1691A, factor II G20210A, and
      methylenetetrahydrofolate reductase [MTHFR] C677T) were analyzed. In addition,
      risk factors for arteriosclerotic vascular disease were assessed. MAIN OUTCOME
      MEASURES: Parameters of thrombophilia. RESULTS: None of the thrombophilic markers
      (genetic and acquired) constituted a significant risk factor for NAION. Ischemic
      heart disease, hypercholesterolemia, and diabetes mellitus were discerned as risk
      factors for NAION with odds ratios of 2.9 (95% confidence interval [CI], 1.3
      6.4), 2.6 (95% CI, 1.2-5.5), and 2.3 (95% CI, 1.1-4.8), respectively. Multiple
      logistic regression analysis indicated that ischemic heart disease and
      hypercholesterolemia exerted an additive risk for NAION with a combined odds
      ratio of 4.5 (95% CI, 1.4-14.5). However, none of these risk factors
      statistically predicted second eye involvement. CONCLUSION: NAION was not found
      to be associated with thrombophilic risk factors, yet it was related to ischemic
      heart disease, hypercholesterolemia, and diabetes mellitus.

PMID- 10201596
TI  - Association of high-dose intravenous methylprednisolone with reversal of
      blindness from lightning in two patients.
AB  - OBJECTIVE: To report possibly beneficial effects of treatment with high-dose
      corticosteroids given intravenously to two patients with loss of vision after
      lightning strikes. DESIGN: Case reports. PARTICIPANTS: Two patients who suffered
      the effects of a lightning strike. INTERVENTION: High-dose intravenous
      methylprednisolone (NASCIS-2 Protocol). MAIN OUTCOME MEASURES: Vision recovery,
      pupil responses, and optic nerve appearance. RESULTS: One patient had unilateral
      ophthalmoscopically visible abnormality with light perception vision and a
      relative afferent defect in that eye; vision recovered to 20/25. The other
      patient had no light perception, nonreactive pupils, and normal fundus
      examinations in both eyes; vision recovered bilaterally to normal (20/20).
      CONCLUSIONS: High-dose intravenous corticosteroid treatment in these patients may
      have had a role in their visual recovery.

PMID- 10201597
TI  - Epidemiologic characteristics and clinical course of patients with malignant
      eyelid tumors in an incidence cohort in Olmsted County, Minnesota.
AB  - OBJECTIVE: To determine the epidemiologic and clinical characteristics of
      patients with malignant eyelid tumors in an incidence cohort. DESIGN: Cohort
      series. PARTICIPANTS: A computerized retrieval system was used to identify all
      patients residing in Olmsted County, Minnesota, who had a newly diagnosed
      malignant eyelid tumor during the 15-year interval from 1976 through 1990. The
      patients' medical records were reviewed for demographic and clinical data.
      INTERVENTION: Surgical excision with frozen-section histopathologic analysis,
      Mohs' micrographic excision, and electrodesiccation and curettage were the
      primary methods of treatment. MAIN OUTCOME MEASURES: Survivorship free of tumor.
      RESULTS: The incidence cohort included 174 patients who each had 1 tumor; men and
      women were equally affected, and all patients were white. Tumors developed most
      commonly on the lower eyelid (n = 85; 48.9%) and in the medial canthal region (n
      = 48; 27.6%) but involved the right and left sides with equal frequency. Of the
      174 tumors, 158 were basal cell carcinomas (90.8%), 15 were squamous cell
      carcinomas (8.6%), and 1 (0.6%) was a malignant melanoma. The age- and gender
      adjusted incidence rates for basal cell carcinoma, squamous cell carcinoma, and
      malignant melanoma were 14.35, 1.37, and 0.08 per 100,000 individuals per year,
      respectively. No cases of sebaceous gland carcinoma were identified. The 5- and
      10-year recurrence rates for all tumors on the eyelid were 2% and 3%,
      respectively. The probability of an unrelated malignancy developing elsewhere in
      the body was approximately 9% at 5 years and 15% at 10 years. CONCLUSIONS: Basal
      cell carcinoma is the most common malignant eyelid tumor in whites. The lower
      eyelid and medial canthus are the most frequent sites of origin. Men and women
      are equally affected. Recurrence after surgical excision is uncommon.

PMID- 10201598
TI  - Sclerosing sweat duct carcinoma of the eyelid margin: unusual presentation of a
      rare tumor.
AB  - OBJECTIVE: Sclerosing sweat duct carcinoma (SSDC) is a rare, slow-growing,
      locally invasive skin tumor of eccrine and pilar origin. It is usually located on
      the face, particularly the upper lip, cheek, and forehead. It has been
      infrequently reported on the eyelid, secondarily involved from adjacent cheek and
      brow tumors. Only four previous cases have reported primary eyelid tumors. The
      authors present four cases of primary eyelid margin involvement, which show the
      variability in clinical presentations. DESIGN: Retrospective case series. The
      authors present four case studies of lower eyelid margin tumors diagnosed as
      SSDC. PARTICIPANTS/METHODS: The history of this recently recognized neoplasm is
      discussed in relation to the cases presented and the role of the ophthalmologist
      and pathologist in such cases. RESULTS: Primary SSDC of the eyelid margin is a
      reportedly rare entity. This particular presentation can occur in all age groups;
      can mimic benign, acanthotic, or basal cell-like tumors; and is usually
      misdiagnosed initially. This can lead to a delay in definitive treatment for a
      tumor that classically presents late in its natural history to health
      professionals. All eight cases of primary eyelid SSDC now reported in the
      literature have occurred in the lower lid. CONCLUSION: This rare but aggressive
      tumor is difficult to diagnose from a simple biopsy and may be more common than
      previously believed. Initial or early diagnosis is important because of unusually
      invasive characteristics. Recurrence is common and usually leads to extensive
      tissue loss via direct invasion or subsequent wide resection. Correct histologic
      diagnosis at the time of initial tumor removal will likely aid in achieving
      complete excision with fewer recurrences.

PMID- 10201599
TI  - Conjunctival lymphoma masquerading as chronic conjunctivitis.
AB  - OBJECTIVE: Malignant lesions of the conjunctiva may present with slowly evolving
      signs resembling inflammation. The authors describe the clinical and
      histopathologic findings of two patients with bilateral conjunctival lymphoma who
      presented with a history of chronic conjunctivitis without clinically noticeable
      subconjunctival nodules. DESIGN: Case report. PARTICIPANTS: Two patients.
      INTERVENTION: Both patients underwent conjunctival biopsy for evaluation of
      persistent conjunctival inflammation that did not respond to various medical
      treatment methods. RESULTS: Histopathologic examination revealed extranodal
      marginal zone B-cell lymphoma (mucosa-associated lymphoid tissue type) in one
      patient and follicle center lymphoma in the other patient. Both patients
      subsequently received radiation therapy and achieved a complete remission with no
      evidence of recurrence in the follow-up period of 20 and 16 months, respectively.
      CONCLUSIONS: Conjunctival lymphoma should be included in the differential
      diagnoses of chronic conjunctivitis. Persisting signs and symptoms of
      conjunctivitis not responding to standard treatment should prompt biopsy.

PMID- 10201600
TI  - Dietary antioxidants and age-related maculopathy: the Blue Mountains Eye Study.
AB  - OBJECTIVE: To assess associations between the stages of age-related maculopathy
      (ARM) and dietary intake of carotene, vitamin C, retinol, and zinc. DESIGN: Cross
      sectional, population-based study. PARTICIPANTS: A total of 3654 subjects 49
      years of age and older from a defined area, west of Sydney, Australia,
      participated. A total of 2900 participants (79.4%) completed accurate food
      records. INTERVENTION: Masked grading of stereoscopic macular photographs,
      detailed interviewer-administered questionnaire, and 145-item self-administered
      food frequency questionnaire. MAIN OUTCOME MEASURES: Late ARM and early ARM were
      diagnosed from photographic grading. RESULTS: The authors found no statistically
      significant associations between ARM and dietary intake of either carotene, zinc,
      or vitamins A or C, either from diet or supplements or from the combined intake
      from diet and supplements. Multivariate-adjusted odds ratios (95% confidence
      interval) were calculated comparing highest to lowest dietary intake quintiles.
      For late ARM, the odds ratios were carotene, 0.7 (range, 0.3-2.0); vitamin A, 1.2
      (range, 0.5-3.3); vitamin C, 1.3 (range, 0.5-3.4); and zinc, 1.0 (range, 0.4
      2.8). For early ARM, the odds ratios were carotene, 0.7 (range, 0.4-1.1); vitamin
      A, 1.2 (range, 0.7-2.0); vitamin C, 0.9 (range, 0.5-1.4); and zinc, 0.8 (range,
      0.5-1.3). No significant trends were apparent. Adjustment for energy intake also
      showed no associations between these antioxidants and ARM. Further, no
      associations were found between increasing intake of foods high in antioxidant
      vitamins and decreasing prevalence of either late or early ARM. CONCLUSIONS: The
      authors found no associations between ARM and dietary antioxidants, either from
      diet alone or including supplements, or from selected foods, in the Blue
      Mountains Eye Study population.

PMID- 10201601
TI  - Treatment of retinal arterial occlusion with local fibrinolysis using recombinant
      tissue plasminogen activator.
AB  - OBJECTIVE: Retinal arterial occlusion is one of the most dramatic problems faced
      by ophthalmologists because of its sudden onset and the severe consequences it
      may have on the visual system. In this study, local intra-arterial fibrinolysis
      (LIF) using recombinant tissue plasminogen activator (rTPA) as a new technique
      for the treatment of retinal arterial occlusion was investigated. DESIGN:
      Retrospective, noncomparative case series. PARTICIPANTS: Strict inclusion and
      exclusion criteria were used to select patients for treatment. Fifty-three
      patients with central retinal artery occlusion (n = 46) or branch retinal
      arterial occlusion (n = 7) were enrolled. INTERVENTION: For a maximum of 3 hours,
      10- to 20-mg rTPA per hour in 50-ml sodium chloride was infused transfemorally by
      catheterization of the ophthalmic artery with a variable stiffness microcatheter.
      MAIN OUTCOME MEASURES: The best-corrected visual acuity for distance by an 18
      line logarithmic table was measured on admission, at 24 hours, and at 3 months
      after intervention. RESULTS: At 3 months, visual acuity had improved in 35 (66%)
      of 53 patients. Twenty-five (47.2%) patients showed an improvement of more than 2
      lines, and in 10 (18.8%) patients, improvements of 1 to 2 lines were observed. No
      change in visual acuity occurred in 12 (22.6%) patients, and in 6 (11.3%)
      patients, the visual acuity deteriorated. The mean occlusion time was 14 hours
      (range, 3-50 hours). No statistically significant correlation was found between
      occlusion time and visual outcome (P > 0.22). In two patients, a temporary slight
      hemiplegia was observed during catheterization, and in one patient, a
      hypertensive crisis after LIF treatment was observed. CONCLUSIONS: The high
      success rate of LIF using rTPA in patients suffering from retinal arterial
      occlusion is supposedly due to a causal effect of rTPA on primary platelet-fibrin
      emboli and secondary thrombi. The local fibrinolytic therapy with rTPA involves
      little risk for patients selected by strict inclusion and exclusion criteria. It
      may be used for the treatment of retinal arterial occlusion even later than 8
      hours after the acute visual loss. However, a successful outcome of the therapy
      depends on the prompt referral by well-informed ophthalmologists; a speedy
      execution of all internal, neurologic, and ophthalmologic diagnostic measures;
      and a prompt therapy.

PMID- 10201602
TI  - Progression of diabetic retinopathy after endophthalmitis.
AB  - OBJECTIVE: To determine the effect of endophthalmitis on diabetic retinopathy.
      DESIGN: Noncomparative case series. METHODS: The records of all consecutive
      patients with endophthalmitis treated between 1992 and 1997 at the Medical
      College of Wisconsin were retrospectively reviewed. Those patients with diabetes
      mellitus were analyzed. PARTICIPANTS: From 77 reviewed records, 11 patients (12
      eyes; 14%) were identified as diabetics with endophthalmitis and were studied.
      MAIN OUTCOME MEASURES: Stage of diabetic retinopathy, time to retinopathy
      progression, and visual acuity. RESULTS: Mean patient age was 68 years, and mean
      duration of diabetes was 11.7 years. Mean patient follow-up was 17 months. Of the
      six cases without evidence of retinopathy before the endophthalmitis, none went
      on to develop retinopathy. Of six eyes with pre-existing nonproliferative
      retinopathy, four showed evidence of progression within 6 months of the
      infection. Three developed severe proliferative disease and macular edema, and
      one developed severe nonproliferative disease. More patients without pre-existing
      retinopathy achieved a final visual acuity of 20/40 or greater. CONCLUSIONS:
      Patients with pre-existing diabetic retinopathy may be at increased risk for
      rapid retinopathy progression and a poorer visual outcome after endophthalmitis.
      These results support the concept that inflammation may exacerbate diabetic
      retinopathy.

PMID- 10201604
TI  - Retinal pigment epithelial dysfunction in human immunodeficiency virus-infected
      patients with cytomegalovirus retinitis.
AB  - OBJECTIVE: Prior clinical observations led the authors to examine
      electrophysiologic measures of retinal (electroretinogram [ERG]) and retinal
      pigment epithelial (electro-oculogram [EOG]) function in patients infected with
      human immunodeficiency virus (HIV) who either had or did not have cytomegalovirus
      (CMV) retinitis in order to determine if the ERG or EOG measures were
      differentially affected in CMV retinitis. DESIGN: Cross-sectional study.
      PARTICIPANTS: Forty-one HIV-infected patients (20 with and 21 without CMV
      retinopathy) were evaluated. INTERVENTION: ERGs and EOGs were recorded. Patients'
      fundi were evaluated by indirect ophthalmoscopy or fundus photography. MAIN
      OUTCOME MEASURES: The ERG a- and b-wave amplitudes and EOG light/dark amplitude
      ratio (L/D ratio) from the eyes of all patients were compared with values 2
      standard deviations from the mean of a normal sample. The area of the retinal
      lesions was estimated from fundus photographs or from careful drawings made
      during indirect ophthalmoscopy. RESULTS: The majority of the eyes (64.5%) of the
      patients with CMV retinitis had subnormal L/D ratios, and most eyes (95%) of
      patients without CMV retinitis had normal L/D ratios. Only six eyes (four with
      and two without CMV retinopathy) had subnormal a-wave amplitudes, and there was
      no significant correlation between a-wave amplitude and the L/D ratio for
      patients with CMV retinitis. Most eyes (80.6%) of the patients with CMV retinitis
      had subnormal b-wave amplitudes, but there was no significant correlation between
      b-wave amplitude and L/D ratio in the patients with CMV retinitis. In three
      patients with CMV retinitis selected to exemplify the range of effects on the ERG
      and EOG, the b-wave amplitude loss was roughly proportional to the area of retina
      visibly affected in indirect ophthalmoscopy. One patient had a nonrhegmatogenous
      retinal detachment. CONCLUSIONS: Middle retinal function, as reflected in the b
      wave amplitude, and retinal pigment epithelial function, as reflected in the L/D
      ratio, were both compromised in CMV retinitis, but the effect on function in the
      two layers of the retina appeared independent because there was no significant
      correlation between the L/D ratio and b-wave amplitude. The decrease in L/D ratio
      was not secondary to loss of photoreceptor function and probably represents a
      dysfunction of the retinal pigment epithelium because there was no significant
      correlation between a-wave amplitude, which was normal in most cases, and L/D
      ratio. The inner retinal pathology of CMV retinitis is visible clinically and was
      associated with decreases in b-wave amplitude in this and previous studies. The
      significant independent retinal pigment epithelial dysfunction demonstrated in
      this study may be an important predisposing factor to retinal detachment in CMV
      retinitis.

PMID- 10201603
TI  - Surgical removal of subfoveal choroidal neovascularization in age-related macular
      degeneration.
AB  - OBJECTIVE: To assess the results of surgical excision of subfoveal choroidal
      neovascularization (CNV) in patients with age-related macular degeneration (AMD).
      DESIGN: Retrospective, interventional, noncomparative case series. PARTICIPANTS
      AND INTERVENTION: Sixty-four consecutive patients undergoing surgical removal of
      AMD-related subfoveal CNV were studied. The surgical method included a small
      retinotomy, subretinal tissue plasminogen activator (t-PA), perfluoro-n-octane,
      and air-fluid exchange. MAIN OUTCOME MEASURES: Final visual acuity was the main
      outcome measure; surgical complications and recurrence rates were also assessed.
      RESULTS: Preoperative visual acuity ranged from 20/100 to 1/200, with a mean of
      20/400. Average follow-up was 19 months. The best acuity achieved after surgery
      ranged from 20/20 to hand motions, with a mean of 20/200. Final visual acuity
      ranged from 20/50 to light perception, with a mean of 20/400. Final acuity was
      improved 3 or more lines in 19 eyes (30%) (median, 5 lines), stable in 27 eyes
      (42%), and 3 or more lines worse in 18 eyes (28%) (median, 4 lines). Factors
      associated with greater visual improvement included poorer initial acuity, larger
      CNV size, and smaller subretinal hemorrhage. Analysis of groups similar to
      Macular Photocoagulation Study subgroups A through D showed an average
      improvement of 1 line for group C (visual acuity, 20/200 or worse; CNV larger
      than 2 disc areas). Other preoperative, intraoperative, and postoperative
      factors, including recurrence and retinal detachment, did not have a significant
      effect on final visual outcome. CONCLUSIONS: After surgical excision of AMD
      related subfoveal CNV, vision improved or stabilized in the majority of patients.
      Surgery may be of greatest value for patients with poorer vision, larger
      subfoveal CNV, and minimal hemorrhage. Further evaluation of this technique
      should be accomplished via completion of a controlled, randomized multicenter
      study.

PMID- 10201605
TI  - Treatment of acanthamoeba keratitis with chlorhexidine.
AB  - OBJECTIVE: To evaluate the efficacy of chlorhexidine solution in the treatment of
      patients with Acanthamoeba keratitis. DESIGN: Prospective nonrandomized study.
      PARTICIPANTS: Five patients infected with culture-proven Acanthamoeba keratitis.
      INTERVENTION: Chlorhexidine solution was used hourly on six eyes and gradually
      reduced to four times a day after 1 month. Follow-up ranged from 1 to 10 months
      (mean, 4 months). MAIN OUTCOME MEASURES: Severity of symptoms and signs, time for
      healing, and final visual acuity. RESULTS: Clinical results in four patients
      showed improved visual acuity, with a rapid recovery within 1 week. No adverse
      drug reaction was encountered, but one patient with a perforated ulcer developed
      glaucoma. Eighty-three percent of 6 eyes were medically cured with chlorhexidine
      and recovered visual acuity 6/18 or better. Four of five patients improved within
      3 weeks, with resolution of infiltration and healing of epithelial defects. By 2
      to 3 weeks, visual acuity 6/18 or better had improved in four (66.7%) of six eyes
      and recovered 6/6 in two eyes (33.3%). Bacterial coinfection occurred in one eye.
      CONCLUSION: Chlorhexidine dramatically hastened clinical improvement in all eyes
      and is a successful medical therapy that has excellent results in patients who
      are diagnosed early.

PMID- 10201606
TI  - Correlation of tear fluorescein clearance and Schirmer test scores with ocular
      irritation symptoms.
AB  - OBJECTIVE: To correlate and compare the Schirmer 1 test and a new method of
      measuring tear fluorescein clearance with the CytoFluor II fluorometer with the
      severity of ocular irritation symptoms, clinical signs of meibomian gland
      disease, corneal fluorescein staining scores, and corneal and conjunctival
      sensitivity. DESIGN: Case-control study. PARTICIPANTS: Forty patients presenting
      with a chief complaint of ocular irritation, and 40 asymptomatic control subjects
      of similar age distribution. INTERVENTION: All subjects completed a symptom
      questionnaire, a baseline ocular examination, fluorescein clearance test (FCT),
      and Schirmer 1 test. MAIN OUTCOME MEASURES: The FCT was performed with a
      CytoFluor II fluorophotometer by measuring the fluorescein concentration in
      minimally stimulated tear samples collected from the inferior tear meniscus 15
      minutes after instillation of 5 microl of 2% sodium fluorescein. Severity of
      ocular irritation was assessed with a symptom questionnaire. Schirmer 1 test,
      biomicroscopic meibomian gland evaluation, corneal fluorescein staining score,
      and corneal and conjunctival sensation scores were assessed with the Cachet
      Bonnet anesthesiometer in all subjects. RESULTS: Irritation symptoms correlated
      with higher log tear fluorescein concentration (symptomatic 3.08 +/- 0.62
      units/,microl, normal control 1.89 +/- 0.7 units/microl, P < 0.005) and lower
      Schirmer 1 test scores (symptomatic 12.6 mm, normal control 22.3 mm, P < 0.005).
      The FCT showed greater predictive value for identifying ocular irritation than
      the Schirmer 1 test. A fluorescein concentration of 274 units//microl eliminated
      80% of the normal subjects (specificity) and identified 85% of the abnormal
      subjects (sensitivity). Log of tear fluorescein concentration and the Schirmer 1
      test correlated with meibomian gland orifice metaplasia (2.81 +/- 0.78
      units/microl and 14.47 +/- 9.53 mm in those with metaplasia vs. 1.83 +/- 0.71
      units/microl and 23.14 +/- 7.67 mm in those without metaplasia, P < 0.001) and
      with the percentage of acinar dropout. Both log of tear fluorescein concentration
      and the Schirmer 1 test correlated with corneal fluorescein staining (Pearson
      correlation of 0.394 P < 0.0001 for Schirmer 1 test and 0.312 P < 0.005 for log
      of tear fluorescein). In addition, log of tear fluorescein and Schirmer 1 test
      scores correlated with corneal and conjunctival sensation scores (Spearman's rho
      for corneal sensation: log of tear fluorescein -0.38, P < 0.003, Schirmer 1 test 
      0.39, P < 0.002, and for conjunctival sensation: log of tear fluorescein -0.391,
      P < 0.001, Schirmer 1 test -0.23, P < 0.061). CONCLUSIONS: The FCT shows a
      greater predictive value for ocular irritation than the Schirmer 1 test. It
      correlates better with age, meibomian gland dysfunction, and decreased corneal
      and conjunctival sensation. Decreased tear clearance was identified as a risk
      factor for ocular irritation, even in subjects with normal Schirmer scores. This
      simple technique may provide new clues into the mechanism and therapy of ocular
      irritation.

PMID- 10201607
TI  - Topical nonpreserved methylprednisolone therapy for keratoconjunctivitis sicca in
      Sjogren syndrome.
AB  - OBJECTIVE: To review the efficacy and side effects of topical nonpreserved
      corticosteroid therapy for treatment of severe keratoconjunctivitis associated
      with Sjogren syndrome. DESIGN: Retrospective, noncomparative case series.
      PARTICIPANTS: Twenty-one patients with Sjogren syndrome-associated
      keratoconjunctivitis sicca and annoying ocular irritation. INTERVENTION:
      Treatment with topical nonpreserved methylprednisolone sodium succinate. MAIN
      OUTCOME MEASURES: Symptom severity, frequency of instillation of artificial
      tears, corneal fluorescein staining scores, resolution of filamentary keratitis,
      steroid-related side effects. RESULTS: Before starting methylprednisolone
      therapy, all patients were experiencing moderate-to-severe eye irritation despite
      prior punctal occlusion in most cases and frequent use of nonpreserved artificial
      tears by all. After 2 weeks of topical application, three to four times per day,
      moderate (43%) or complete (57%) relief of irritation symptoms was experienced by
      all patients and no complications were observed. An average decrease in corneal
      fluorescein scores of 2.6 +/- 0.5 points (on a 12-point scale) was observed, and
      filamentary keratitis resolved in all ten eyes with this condition. Therapy was
      stopped after 2 weeks in eight patients, and six of these patients reported that
      their symptoms remained at a tolerable level for weeks to months. Lower dose
      steroid therapy was continued in the remaining patients, whose symptoms worsened
      after attempted weaning. Complications of corticosteroid therapy in patients
      receiving prolonged therapy included increased intraocular pressure in one
      patient at 3 months, worsening of pre-existing posterior subcapsular cataracts in
      one patient at 6 months, and formation of posterior subcapsular cataracts in
      another patient at 6 months. CONCLUSIONS: These findings indicate that topical
      nonpreserved methylprednisolone is an effective treatment option for patients
      suffering from severe keratoconjunctivitis sicca who continue to experience
      bothersome eye irritation despite maximum aqueous enhancement therapies. They
      also suggest that inflammation is a key pathogenic factor in this condition.
      Careful monitoring is essential in dry eye patients treated with corticosteroids
      for more than 2 weeks because steroid-related complications (increased
      intraocular pressure and cataract formation) were observed after several months
      of therapy in this series. Because of the chronic nature of this disease and the
      likelihood of patients developing steroid-related complications with their long
      term use, topical nonpreserved methylprednisolone therapy appears to be most
      appropriate for short-term "pulse" treatment of exacerbations of
      keratoconjunctivitis sicca.

PMID- 10201608
TI  - A comparative study of recurrent pterygium surgery: limbal conjunctival autograft
      transplantation versus mitomycin C with conjunctival flap.
AB  - OBJECTIVE: To compare the recurrence rate following treatment of recurrent
      pterygia using one of two techniques-limbal conjunctival autograft
      transplantation versus low-dose intraoperative mitomycin C (0.2 mg/ml) combined
      with conjunctival flap closure. DESIGN: Randomized clinical trial. PARTICIPANTS:
      Eighty-one patients with recurrent pterygia treated by limbal conjunctival
      autograft transplantation (n= 41) or mitomycin C combined with conjunctival flap
      (n= 40) participated. INTERVENTION: Limbal conjunctival autograft transplantation
      or low-dose intraoperative mitomycin C application with conjunctival flap
      technique was performed on recurrent pterygium cases. MAIN OUTCOME MEASURES:
      Recurrence of pterygium and postoperative complications. RESULTS: During mean
      follow-up periods of 16+/-1.9 and 15.5+/-1.5 months, six recurrences (14.6%) in
      the limbal conjunctival autograft transplantation group and five recurrences
      (12.5%) in the mitomycin C group were observed (P=0.77). The difference between
      the mean ages of recurrent (26.4+/-8.0 years) and nonrecurrent (35.8+/-11.9
      years) cases for all patients was statistically significant (P=0.014).
      Technically, limbal conjunctival autograft transplantation seemed to be more
      difficult. The most frequent complication in limbal conjunctival autograft
      transplantation was graft edema, whereas that in the mitomycin C group was
      superficial keratitis. CONCLUSION: Both techniques showed similar recurrence
      rates in the treatment of recurrent pterygia. Although technically easier to
      perform, further follow-up is necessary to determine the long-term safety of low
      dose intraoperative mitomycin C with conjunctival flap closure. The surgeon's
      familiarity with either procedure should determine the method of choice.

PMID- 10201609
TI  - Limbal allografting from related live donors for corneal surface reconstruction.
AB  - OBJECTIVE: To report the results of limbal allograft transplantation, from human
      leukocyte antigen (HLA)-matched and -unmatched related live donors, in patients
      with ocular surface disease due to chemical burns and Stevens-Johnson syndrome.
      DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Eight patients
      (nine eyes) with severe chemical burns (n = 7 eyes) and Stevens-Johnson syndrome
      (n = 2 eyes). INTERVENTION: Recipient eyes were treated with excision of
      cicatricial tissues. Transplantation of superior and inferior limbal grafts was
      performed from related live HLA-matched (n = 7) and -unmatched donors (n = 2).
      Systemic cyclosporine was not used in any of the recipients. MAIN OUTCOME
      MEASURES: Reconstruction of corneal surface epithelium, restoration of
      avascularity, increase in ocular comfort, and improvement in visual acuity.
      RESULTS: With a mean observation period of 17.2 months, phenotypically corneal
      epithelium, decreased vascularization of the corneal surface, and improved ocular
      comfort were seen in seven (77.8%) eyes. In all seven eyes, gradual recurrence of
      peripheral corneal vascularization occurred during the follow-up period. Features
      of graft rejection developed in three (42.9%) of these seven eyes. In two eyes,
      limbal transplantation from HLA-unmatched donors failed to reconstitute the
      corneal surface. Limbal allograft transplantation resulted in visual acuity of
      20/400 or greater in only two (22.2%) eyes at last follow-up. Corneal grafts
      performed 7 and 16 months after successful limbal transplantation in two eyes
      developed recurrent epithelial breakdown and superficial corneal scarring. None
      of the donor eyes in this study had any complication. CONCLUSION: Transplantation
      of limbal tissue from related live donors successfully reconstructs the corneal
      surface in HLA-matched recipients. Recurrence of vascularization on long-term
      follow-up probably results from inadequate stem cell transfer, immune-mediated
      stem cell damage, or both. Limbal allografting is best performed by transplanting
      the entire limbus from a cadaveric donor eye with systemic immunosuppression of
      the recipient, even if the donor is HLA-compatible.

PMID- 10201610
TI  - Oversized grafts in children.
AB  - OBJECTIVE: To evaluate the efficacy of oversized corneal grafts in the pediatric
      age group. DESIGN: Prospective, nonrandomized clinical trial. PARTICIPANTS AND
      INTERVENTION: Forty pediatric patients with unilateral or bilateral corneal
      opacification of congenital or acquired origin underwent corneal grafting surgery
      over a period of 2 years using donor corneal buttons oversized by 1 mm. MAIN
      OUTCOME MEASURES: The parameters evaluated were indications for keratoplasty,
      graft clarity, visual acuity, keratometry, spherical equivalent, anterior chamber
      depth, and complications. RESULTS: Corneal ulceration was the most common cause
      of corneal opacification (25%), followed by trauma (20%) and sclerocornea (20%).
      At 1 year, clear grafts were achieved in 85% of the cohort. The average
      keratometry at the end of 1 year was 43.28 +/- 1.65 diopters (D) in the
      congenital opacity group and 43.04 +/- 2.20 D in the acquired group. The
      keratometric astigmatism was 3.60 +/- 2.60 D in the congenital group and 2.52 +/-
      2.20 D in the acquired group. Oversized grafts provided an adequate anterior
      chamber depth of 2.20 +/- 0.612 mm in the congenital group and 2.36 +/- 0.302 mm
      in the acquired group. Visual acuity of 20/80 or better was recorded in only 30%
      of cases in the congenital group as opposed to 47% with acquired opacities. Nine
      cases had episodes of graft rejection. CONCLUSION: Oversizing donor buttons by 1
      mm provides adequate anterior chamber depth and increases the morphologic success
      of corneal grafting in children.

PMID- 10201611
TI  - Long-term results of corneal graft survival in infants and children with peters
      anomaly.
AB  - OBJECTIVE: To determine the long-term results of corneal graft survival after
      penetrating keratoplasty for Peters anomaly and to identify risk factors for
      graft failure. DESIGN: Noncontrolled interventional case series: a single-center
      retrospective review of a consecutive surgical series. PARTICIPANTS: The records
      of all children 12 years of age or younger who underwent penetrating keratoplasty
      for Peters anomaly between January 1971 and December 1992 were reviewed. All
      study eyes had completed a minimum of 3 years of follow-up from the date of first
      keratoplasty and had undergone most of their corneal surgery at Emory University.
      INTERVENTION: Characteristics of the recipient, the eye, the donor, and the
      surgical procedure were analyzed for their influence on survival of the first
      graft. Survival probabilities were estimated using the Kaplan-Meier method.
      Multivariate regression analysis was performed to estimate relative risks and
      adjusted survival probabilities. MAIN OUTCOME MEASURE: Graft clarity. RESULTS:
      One hundred forty-four penetrating keratoplasties were performed in 72 eyes of 47
      patients. The median age at first keratoplasty was 4.4 months. The median follow
      up was 11.1 years. Fifty-four percent of eyes received one graft, 18% received
      two grafts, and 28% received three or more grafts. The overall probability of
      maintaining a clear first graft was 56% at 6 months, 49% at 12 months, 44% at 3
      years, and 35% at 10 years. The probability of second or subsequent grafts
      surviving for 3 years was less than 10%. Thirty-nine percent of eyes had a clear
      graft at the time of review; 36% of eyes had a clear first graft. Multivariate
      analysis identified disease severity, donor cornea size, coexisting central
      nervous system abnormalities, and quadrants of anterior synechiae as the
      strongest risk factors for graft failure. Supplemental multivariate analysis,
      restricted to observable preoperative variables, identified stromal vessels,
      total limbal opacification, and preoperative glaucoma as independent preoperative
      predictors of graft failure. Allograft rejection was the most frequently
      identified cause of graft failure. Major complications after keratoplasty were
      phthisis, retinal detachment, cataract, and glaucoma. CONCLUSIONS: The overall
      long-term probability of maintaining a clear graft after initial penetrating
      keratoplasty for Peters anomaly is 35% +/- 0.06%, with subsequent grafts rarely
      surviving. Eyes with severe disease, larger donor corneas, coexisting central
      nervous system abnormalities, and anterior synechiae have significantly poorer
      outcomes than eyes without these factors. These data should be carefully
      considered before recommending corneal transplantation for Peters anomaly,
      particularly after previous graft failure.

PMID- 10201612
TI  - Vision screening of preverbal children with Teller acuity cards.
AB  - OBJECTIVE: To evaluate the modified Teller visual acuity test as a mass screening
      tool for testing visual acuity in infants and preverbal children. DESIGN:
      Prospective case series. PARTICIPANTS: A total of 1126 healthy children
      undergoing mandatory examination at the Mother and Child Health Center.
      INTERVENTION: Visual acuity was tested by the modified Teller visual acuity test.
      MAIN OUTCOME MEASURES: Visual acuity was measured in all children. Clinical
      evaluation was performed in children who failed the Teller acuity test and in a
      control group. RESULTS: Visual acuity was below the normal range in 5% of the
      children. In the study group referred for complete eye examination, there were 9%
      false-negative and 44% false-positive results. In the age range of 12 to 17
      months, false-negative and false-positive results were obtained in 5.6% and 50%
      of the children, respectively. CONCLUSIONS: The Teller acuity card procedure can
      be used for vision screening in preverbal children. Testing was associated with a
      high rate of false-positive results.

PMID- 10201613
TI  - Fas expression and apoptosis correlate with cardiac dysfunction in patients with
      dilated cardiomyopathy.
AB  - Fas is a transmembranous glycoprotein that mediates apoptosis. To elucidate the
      roles of Fas and of myocyte apoptosis in patients with dilated cardiomyopathy
      (DCM), the expression of Fas and the fragmentation of DNA were compared in
      endomyocardial biopsy specimens obtained from patients with DCM. Endomyocardial
      biopsy was performed on 19 subjects (16 with DCM and 3 control subjects) who also
      underwent cardiac catheterization and echocardiography. Fas and bcl-2 expression
      were assayed immunohistochemically, and in situ TdT staining was performed to
      estimate the number of apoptotic cells. Samples from the DCM patients stained
      more intensely with anti-Fas antibody than those from control patients (p<0.05).
      The percentage of in situ TdT-positive cells was significantly higher in the DCM
      group than in the control group (p<0.05). A correlation between Fas expression
      and in situ TdT staining was observed in 67% of myocytes in the DCM group.
      Moreover, the percentage of in situ TdT staining was significantly higher in
      subjects with severely impaired left ventricular systolic function than in those
      whose systolic function was mild to moderately impaired, or who had normal
      systolic function (p<0.05). The samples showed little expression of bcl-2. These
      results suggest that Fas expression and apoptosis may be involved in the
      progression of cardiac dysfunction in DCM.

PMID- 10201614
TI  - New method of estimating myocardial infarct size using technetium-99m
      pyrophosphate and thallium-201 dual single photon emission computed tomography
      imaging.
AB  - A new method was devised to estimate infarct size using dual single photon
      emission computed tomography with thallium-201 and technetium-99m pyrophosphate.
      Designating the ratio of infarct area to whole myocardial volume as %MI, the
      correlation of %MI with other markers of left ventricular dysfunction was
      examined: peak creatine kinase, ejection fraction and left ventricular asynergy.
      As %MI correlated well with these markers, it is considered that %MI will be
      useful for estimating infarct size and predicting the severity of left
      ventricular dysfunction in the early stage of acute myocardial infarction.

PMID- 10201615
TI  - Disopyramide improves hypoxia in patients with tetralogy of Fallot through a
      negative inotropic action.
AB  - The hemodynamic and right ventricular volumetric effects of disopyramide were
      investigated in patients with tetralogy of Fallot (TF). Intracardiac pressure and
      oxygen saturation were measured, before and after intravenous administration of
      disopyramide (2 mg/kg) in 7 patients who had not had previous surgery. Right
      ventricular volume and the diameter of its outflow tract were analyzed in these 7
      and in a further 4 patients with a previous shunt. Aortic oxygen saturation
      increased from 90.4+/-7.5 (mean+/-SD) to 94.1+/-5.5% (p<0.05) with an increase in
      pulmonary blood flow and pressure. The systolic pressure gradient between the
      main pulmonary artery and the right ventricle decreased from 59+/-8 to 42+/-9
      mmHg (p<0.01). Aortic pressure fell from 77+/-5 to 67+/-4 mmHg (p<0.05). Systemic
      vascular resistance increased from 15.3+/-2.2 to 19.4+/-3.3 u x m2 (p<0.05).
      Pulmonary vascular resistance remained unchanged. The diastolic and systolic
      diameter indices of the right ventricular outflow tract increased from 17.8+/-3.8
      to 20.5+/-3.4 and from 6.5+/-3.0 to 10.4+/-2.2 mm/m2, respectively (p<0.01),
      whereas the right ventricular ejection fraction decreased. Disopyramide improves
      systemic oxygen saturation in patients with TF through its negative inotropic
      action on the right ventricle.

PMID- 10201616
TI  - Strategy for balancing anticoagulation and hemostasis in aortocoronary bypass
      surgery: blood conservation and graft patency.
AB  - The minimal effective dose of aprotinin on hemostasis under normothermic
      perfusion, the influence of anticoagulant therapy on graft patency, and the
      thromboembolic and hemorrhagic events were investigated after aortocoronary
      bypass graft operation (CABG). One hundred CABG patients under normothermic
      perfusion were randomly divided into the following groups: (1) coumadin plus
      acetylsalicylic acid (ASA) (n=32); no aprotinin used during cardiopulmonary
      bypass (CPB); (2) minimal-dose, 10(6) KIU during CPB, aprotinin used, followed by
      ASA and coumadin (n=36); and (3) very low-dose, total of 2x10(6) KIU before CPB
      and during CPB; aprotinin used; anticoagulation therapy with heparin early after
      surgery and followed by replacement with ASA and coumadin (n=32). The patency of
      arterial grafts was 100% in all groups. The patency of vein grafts was 95-98% and
      there was no difference among the groups. The blood loss was significantly
      reduced in both aprotinin groups (groups 2 and 3) compared to the coumadin plus
      ASA group, although no difference existed between the 2 aprotinin groups.
      Postoperative thrombotic and hemorrhagic events were not observed in any group.
      From this study, it was concluded that 10(6) KIU aprotinin in pump-prime-only
      followed by oral ASA and coumadin was the recommendation from the benefit/cost
      consideration.

PMID- 10201617
TI  - Analysis of the treatment of acute myocardial infarction using ambulance records
      in Japanese cities.
AB  - By means of ambulance records, the current state of medical services for the
      treatment of acute myocardial infarction (AMI) was investigated in Chiba City and
      Ichihara City, Japan. From all patients transported by ambulance personnel in
      1992 (n=31,191), 388 patients who were admitted within 2 weeks after the onset
      were studied. Types of admitting institution, diagnoses, medical treatments and
      prognoses were investigated. According to medical records, 168 patients fulfilled
      the criteria of definite AMI and were admitted alive. Percutaneous transluminal
      coronary angioplasty (PTCA) and recanalization (PTCR) were performed on 54 and 6
      patients, respectively. The hospital case-fatality rates were lower in the
      patients who underwent emergency PTCA or PTCR than in the others. Emergency PTCA
      or PTCR, and admission to coronary care units (CCU) or institutions equipped with
      coronary angiography, decreased the fatality risk, even after considering age,
      sex, and disease severity. These results show the importance of the selection of
      institutions for AMI patients. Because 40% of definite AMI patients were sent to
      institutions without CCU, it is essential that enough CCU are available through
      an improvement in cooperation between the various types of institutions, and in
      the proper transfer of AMI patients to CCU

PMID- 10201618
TI  - Radiofrequency catheter ablation for sinoatrial node reentrant tachycardia:
      electrophysiologic features of ablation sites.
AB  - The aim of this study was to investigate catheter ablation of sino-atrial
      reentrant tachycardia (SART) and the electrophysiologic characteristics of the
      ablation sites. From January 1990 to October 1997, 651 patients with
      supraventricular tachycardia were referred and 11 patients were found to have
      SART. Ablation was successful in all cases with a mean number of 3.3
      radiofrequency (RF) current pulses. SART terminated during 22 of 36 RF pulses. In
      spite of prompt termination, tachycardia could be re-induced in 3 of 11 patients
      with its earliest activation site shifted. At effective ablation sites, the
      electrograms during tachycardia were characterized as fractionated (75+/-17 ms),
      and 38+/-16 ms prior to surface P wave, and 42+/-18 ms prior to the high right
      atrium. Unipolar electrograms revealed a sharp negative unipolar deflection, so
      called QS pattern, in 15 of 20 sites during SART and 15 of 15 sites during sinus
      rhythm. During effective applications, atrial premature beats (APB) with
      activation sequences identical to sinus rhythm appeared in 14 of 22 cases.
      Effective ablation sites of SART showed fractionated electrograms during
      tachycardia and sinus rhythm. Unipolar electrogram with a QS pattern and APB
      during energy application could be an indicator of the optimal ablation sites.

PMID- 10201619
TI  - Favorable life-style modification and attenuation of cardiovascular risk factors.
AB  - In order to develop an effective counseling system for prevention of
      cardiovascular diseases, the association of a favorably changed life-style with
      improved risk factors was examined. Participants were 7,321 office workers aged
      30-69 years from in and around Nagoya city. The age-adjusted odds ratio (OR) and
      its 95% confidence interval (CI) were calculated to assess the likelihood of risk
      factor improvement by favorable life-style modifications during a 3-year period.
      Those who began to eat breakfast and increased their vegetable intake normalized
      their previously abnormal diastolic blood pressure with more than twice the
      likelihood (adjusted OR [95% CI] 2.89 [1.29-6.46] and 2.60 [1.18-5.75],
      respectively). 'Began to eat breakfast' was also significantly associated with
      normalized total cholesterol (TC) (1.84, [1.05-3.21]). 'Stopped eating till full'
      significantly normalized the body mass index (2.03; [1.25-3.28]), uric acid
      (1.65; [1.07-2.52]) and TC (1.43; [1.04-1.97]). Those who started regular
      exercise significantly normalized their high-density lipoprotein-cholesterol (HDL
      C) abnormality with 1.69-times the likelihood (1.69; [1.24-2.29]) and those who
      began to walk briskly also improved their TC abnormality (1.85; [1.19-2.89]). HDL
      C was normalized with 2.55-times the likelihood in those who quit smoking (2.55;
      [1.68-3.86]). Because favorable life-style modifications can attenuate abnormal
      cardiovascular risk factors, then proper advice on specific risk factors should
      be routinely given at each health check-up in order to prevent the onset of
      cardiovascular diseases in subsequent years.

PMID- 10201620
TI  - Effect of intravenous amiodarone on electrophysiologic variables and on the modes
      of termination of atrioventricular reciprocating tachycardia in Wolff-Parkinson
      White syndrome.
AB  - Atrioventricular reciprocating tachycardia (AVRT) associated with the Wolff
      Parkinson-White (WPW) syndrome, sometimes terminates spontaneously, generally
      sustains and eventually becomes drug resistant. Amiodarone is a potent
      antiarrhythmic drug that is sometimes effective in patients with AVRT which is
      resistant to conventional antiarrhythmic drugs. However, systematic studies
      concerning the effects of amiodarone on AVRT have not been reported. This study
      evaluated the effects of intravenous amiodarone on electrophysiologic variables,
      and on the sites and the modes of termination of AVRT. Fifteen WPW patients were
      studied. Nine had overt, and 6 had concealed WPW syndrome. Measurements of
      electrophysiologic variables and the induction of AVRT were performed by atrial
      and/or ventricular programmed stimulations. Amiodarone was then administered at a
      dose of 5 mg/kg over 5 min. The effective refractory periods (ERP) of the atrial,
      atrioventricular node, ventricular and accessory pathway were increased
      significantly by amiodarone. The conduction times of all the components were
      significantly lengthened by amiodarone, except for the His-ventricular (HV)
      interval in concealed WPW patients. AVRT was induced in all patients, and was
      terminated by amiodarone in 12 of 13 patients with sustained AVRT. After
      amiodarone, AVRT was induced in 9 patients. Spontaneous termination was observed
      11 times in 3 of the 9 patients in whom AVRT was still induced. In these cases,
      the modes and sites of termination were the same as during the baseline state.
      The ERPs and conduction times of all components of AVRT, except the HV interval,
      were significantly lengthened by amiodarone. Amiodarone is efficacious for
      terminating AVRT wherever weak links exist. However, sites of spontaneous
      termination are not significantly affected by amiodarone.

PMID- 10201621
TI  - Left ventricular end-systolic wall stress is a potent prognostic variable in
      patients with dilated cardiomyopathy.
AB  - Dilated cardiomyopathy is an important cause of morbidity and mortality among
      patients with heart failure. Left ventricular dilation is viewed as a
      compensatory response to maintain stroke volume, and left ventricular dilation is
      directly related to the increase of wall stress. However, only a few studies have
      examined whether wall stress can be a prognostic variable in patients with
      dilated cardiomyopathy. This study was designed to elucidate whether left
      ventricular systolic wall stress was related to the prognosis in patients with
      dilated cardiomyopathy. Twenty-five normal control subjects and 68 patients with
      dilated cardiomyopathy participated in this study. Hemodynamic parameters and
      left ventricular systolic wall stress were determined using echocardiography. In
      addition, the extent score determined by thallium-201 myocardial scintigraphy was
      measured as an index of cumulative loss of myocardium. During the 53-month follow
      up period, 13 patients died of cardiac events. In a stepwise multivariable
      analysis, end-systolic wall stress and fractional shortening were significant
      predictors of survival. The extent score was markedly greater in the patients who
      died than in alive patients. There was a significant correlation between end
      systolic wall stress and extent score (r=0.501, p=0.0001). Left ventricular end
      systolic wall stress is an important predictor of mortality in patients with
      dilated cardiomyopathy.

PMID- 10201622
TI  - Ventricular fibrillation and shortening, alternans and after-depolarizations of
      epicardial monophasic action potentials during coronary occlusion and
      reperfusion: effect of repetition of ischemia.
AB  - The relationship between the occurrence of ventricular fibrillation (VF) and
      repolarization abnormalities of the ischemic and reperfused myocardium is poorly
      understood. The present study examined the temporal relationship between ischemia
      and reperfusion-induced changes in monophasic action potential (MAP)
      configurations and the occurrence of VF, and assessed the effects of repetition
      of ischemia. The left anterior descending coronary artery of 32 anesthetized dogs
      was occluded twice for 5 min, 30 min apart, during constant atrial pacing while
      recording MAPs from the epicardial ischemic zone. During the first occlusion,
      shortening of the MAP duration at 90% repolarization (APD90) and an increase in
      MAP alternans, defined as the maximal difference in APD90 between 2 consecutive
      beats, were observed. Afterdepolarizations also occurred transiently in 35% of
      the animals during occlusion and in 29% upon reperfusion. VF occurred in 28%
      (9/32 of the dogs) during the first sequence, and the incidence was higher in the
      subgroups with maximal alternans > or =20 ms (p<0.05), maximal shortening rate >
      or =30%, and afterdepolarizations. During the second sequence, the incidence of
      VF was reduced to 9% (3/32, p<0.05), associated with a significant reduction in
      the MAP changes. Thus, repolarization abnormalities of the ischemic and
      reperfused myocardium appear to be related to the occurrence of VF. The
      amelioration of the repolarization abnormalities by repetition of ischemia may be
      involved in its antifibrillatory effect.

PMID- 10201623
TI  - Assessment of the temporal relationship between left ventricular relaxation and
      filling during early diastole using pulsed Doppler echocardiography and tissue
      Doppler imaging.
AB  - The study investigated the temporal relationship between left ventricular (LV)
      relaxation and filling during early diastole. The transmitral flow (TMF) velocity
      by pulsed Doppler echocardiography and LV wall motion velocity by pulsed tissue
      Doppler imaging (TDI) were evaluated in 57 patients with various heart diseases
      and 33 normal controls. The patients were classified into 2 groups according to
      the ratio of the peak early diastolic to atrial systolic TMF velocity (E/A): (1)
      the high A group included 44 patients with an E/A < or = 1, and (2) the
      pseudonormalization group included 13 patients with an E/A > 1. The isovolumic
      relaxation time (IRT) from the aortic component of the second heart sound (IIA)
      to the onset of the E wave of the TMF was measured. The peak early diastolic
      velocity of the LV posterior wall (Ew) and time from the IIA to the onset of the
      early diastolic wave (IIA-Ewo) were determined from the LV wall motion velocity
      assessed by pulsed TDI. The Ew was lower in the pseudonormalization and high A
      groups than in the control group. The IIA-Ewo was significantly longer in the
      pseudonormalization and high A groups than in the control group. The time
      constant of the LV pressure decay at isovolumic diastole (tau) correlated
      negatively with the Ew, and correlated positively with the IIA-Ewo in all groups.
      The IIA-Ewo was equal to or shorter than the IRT in control subjects, and was
      longer than the IRT in patients in the pseudonormalization group. In conclusion,
      the temporal relationship between LV relaxation and filling during early diastole
      varied according to the subjects' hemodynamic status. Analysis of TMF by pulsed
      Doppler echocardiography and LV wall motion velocity by pulsed TDI was useful for
      detailed evaluation of early diastolic LV hemodynamics.

PMID- 10201624
TI  - Myocardial stunning caused by sympathetic nerve injury after an operation on
      cervical vertebrae.
AB  - In this case, electrocardiographic inverted T waves appeared after cervical
      laminaplasty and echocardiogram showed temporary wall motion abnormality.
      Myocardial metaiodobenzylguanidine (MIBG) uptake was obviously reduced in the
      same area where the wall motion abnormalities appeared in the echocardiogram,
      although no abnormalities were detected with myocardial thallium scintigraphy and
      coronary angiography. The myocardial stunning was caused by injury to the
      sympathetic nerves from a surgical procedure on the cervical vertebrae.

PMID- 10201625
TI  - Pilsicainide intoxication in a patient with dehydration.
AB  - An 81-year-old woman developed pilsicainide intoxication associated with
      dehydration. The patient had been taking pilsicainide (100 mg/day) for 1 year
      because of paroxysmal atrial fibrillation. Her renal function was within normal
      limits. One week before admission, she was suffering from pneumonia, and had
      appetite loss, fever, and severe fatigue. Physical examination revealed
      dehydration. The electrocardiogram (ECG) on admission showed atrioventricular
      dissociation, idioventricular rhythm with marked QRS widening and QTc
      prolongation. The plasma concentration of pilsicainide on admission was markedly
      elevated at 6.2 microg/ml, approximately 6 times the therapeutic range (0.25-1.0
      microg/ml). Continuous saline infusion was initiated for the treatment of
      dehydration,which progressively improved. As a result, sinus rhythm was recovered
      2 h after admission, and the QRS and JT intervals gradually normalized. This is
      an interesting case because the proarrhythmia of pilsicainide was induced by
      dehydration.

PMID- 10201626
TI  - Radiofrequency catheter ablation of coexistent atrioventricular reciprocating
      tachycardia and left ventricular tachycardia originating in the left anterior
      fascicle.
AB  - Coexistence of supraventricular tachycardia and ventricular tachycardia is rare.
      A patient with no structural heart disease and wide QRS complex tachycardia with
      a right bundle block configuration and right-axis deviation underwent
      electrophysiological examination. A concealed left atrioventricular pathway (AP)
      was found, and atrioventricular reciprocating tachycardia (AVRT) and left
      ventricular tachycardia (VT) originating in or close to the anterior fascicle of
      the left ventricle were both induced. Radiofrequency (RF) catheter ablation of
      the concealed left AP was successfully performed. Ten months later, VT recurred
      and was successfully ablated using a local Purkinje potential as a guide.
      Coexistent AVRT and idiopathic VT originating from within or near the left
      anterior fascicle were successfully ablated.

PMID- 10201627
TI  - Penetrating atherosclerotic ulcer at the proximal aorta complicated with cardiac
      tamponade and aortic valve regurgitation.
AB  - A 56-year-old man had a penetrating atherosclerotic ulcer originating in the
      proximal ascending aorta, which is an unusual case of penetrating aortic ulcer
      complicated with the aortic valve regurgitation and cardiac tamponade. This
      hemodynamically unstable patient was successfully treated by conservative
      management to control his blood pressure and was also monitored closely with
      follow-up imaging studies.

PMID- 10201628
TI  - Natural history and prognostic factors for survival in patients with acquired
      immune deficiency syndrome (AIDS)-related primary central nervous system lymphoma
      (PCNSL).
AB  - The incidence of primary central nervous system lymphoma (PCNSL) is increasing
      rapidly. It will be the most common primary malignant neoplasm of the brain by
      the year 2000. PCNSL is an important lethal complication in acquired
      immunodeficiency syndrome (AIDS) patients. Our objective was to study the natural
      history and prognostic factors for survival in patients with AIDS-related PCNSL.
      This is a retrospective cohort study of 75 patients with the diagnosis of AIDS
      related PCNSL followed at Jackson Memorial Hospital/University of Miami. Medical
      records were abstracted for information about age, gender, race, and ethnicity.
      The method of diagnosis, treatment, and outcome of AIDS and PCNSL in this group
      were examined. Univariate and multivariate analyses were performed to identify
      prognostic factors for survival. The median age was 37 years. Males comprised 84%
      of the patients and 55% of the patients were Hispanic. The most common human
      immunodeficiency virus (HIV) risk factors were homosexuality and multiple sexual
      partners. The median cluster designation (CD) 4 count was 15/microl and the
      median lactic dehydrogensase (LDH) was 1.5x normal. Computed-assisted tomographic
      (CT) scans of the brain showed multiple lesions in 44% of the patients. Single
      photon emission CT scan (SPECT) Thallium-201 of the brain was performed in two
      thirds of patients. The most common histologies were immunoblastic and large cell
      lymphoma. Cranial radiation was given to 72% of the patients, and 55% of them did
      not complete treatment. The median survival of the group was 1.3 months.
      Univariate and multivariate analysis showed that longer survival was associated
      with good performance status (ECOG = 1 to 2 vs. 3 to 4). The presence of prior
      opportunistic infections, risk factors for AIDS, CD4 counts, level of LDH,
      ethnicity, gender, duration of symptoms before diagnosis, and race did not
      influence survival. PCNSL is a neoplasm with a very poor prognosis and short
      survival even with CNS radiation therapy. Performance status appears to be the
      main prognostic factor for survival. No significant differences in presentation
      or outcome were detected between the Hispanic and non-Hispanic patients.

PMID- 10201629
TI  - Primate retroviruses and oncogenesis.
AB  - This review summarizes the current knowledge and role of human and nonhuman
      primate retroviruses in the pathogenesis of neoplasia.

PMID- 10201630
TI  - An immune regulatory cytokine receptor and glioblastoma multiforme: an unexpected
      link.
AB  - Human high-grade gliomas (HGG) are one of the most devastating human
      malignancies. They are rapidly progressing heterogenous tumors for which no
      curable treatment is available. Although these tumors are believed to be of glial
      cell origin, known tumor-specific markers do not characterize them. The specific
      environmental conditions that cause or promote the development of HGG are not
      known. The pathomechanism of HGG is yet to be revealed, although more specific
      genetic alterations are assigned to HGG. Recently, we have found that HGG
      overexpress a receptor for an immune regulatory cytokine, interleukin-13 (IL-13).
      In fact, it appears that all patients with glioblastoma multiforme may possess
      this receptor. IL-13 is an antiinflammatory cytokine with many overlapping
      functions to its homologue, IL-4. There is a high degree of specificity of the
      overexpression of the IL-13 receptor in HGG. This receptor is not only
      quantitatively but also qualitatively different from the only known functional
      signaling receptor for IL-13 of normal tissue. It is not shared with IL-4. The
      more restrictive receptor for IL-13 thus may represent a new factor specific for
      a disease as heterogenous as HGG.

PMID- 10201631
TI  - Is central nervous system prophylaxis necessary in ocular adnexal lymphoma?
AB  - PURPOSE: To examine the frequency of metastasis to the eye and central nervous
      system (CNS) from ocular adnexal lymphomas and to evaluate whether CNS
      prophylaxis is appropriate for these tumors. PATIENTS AND METHODS: Seventy-one
      patients with biopsy-confirmed ocular adnexal lymphomas were evaluated between
      1989 and 1995. The lymphomas were subclassified histopathologically according to
      the new Revised European-American Lymphoma (REAL) criteria. Molecular genetic
      analysis of tumor cell DNA was done by Southern blot. Patients had a complete
      ophthalmologic evaluation and metastatic work-up and were then routinely followed
      up by an ophthalmologist and a medical oncologist. RESULTS: The 34 men and 37
      women studied had a median age of 67 years (23 to 92). Ocular adnexal lymphomas
      were situated in the orbit in 54 patients, in the conjunctiva in 14 patients, and
      in the eyelid in 3 patients. Bilateral involvement occurred in 11 patients. The
      most common histologic diagnoses were (54 patients, 76%) extra-nodal marginal
      zone lymphomas and small lymphocytic lymphomas in 10 patients (14%). Molecular
      genetic analysis performed in all patients confirmed a monoclonal B-cell
      population in 55 patients (77%), including a single rearrangement of the
      immunoglobulin heavy chain gene in 14 patients, and more than two rearrangements
      in 41 patients. No patients had isolated T-cell gene rearrangements. Localized
      ocular adnexal lymphoma was diagnosed in 43 patients (61%), 17 patients (24%)
      were found to have concurrent extraocular lymphoma on metastatic work-up and 11
      patients (15%) had a previous diagnosis of systemic lymphoma before the onset of
      their ocular tumor. The median duration of follow-up was 20 months. Overall, 32
      patients (45%) had tumors, which remained localized to the orbit adnexa. Eleven
      patients (15%) relapsed, but none had eye or central nervous system involvement
      nor required CNS-directed therapy. Although eight patients died, only two died as
      a direct result of systemic lymphoma. No patient received CNS prophylaxis with
      either intrathecal chemotherapy and/or radiation therapy. CONCLUSION: Ocular
      adnexal lymphomas are rare non-Hodgkin's B-cell lymphomas. Metastatic involvement
      of the eye or central nervous system is rare and CNS prophylaxis with
      radiotherapy or chemotherapy is unnecessary.

PMID- 10201632
TI  - General biological aspects of oncogenesis.
AB  - Both genetic and epigenetic events play an important role in oncogenic processes.
      This review discusses the four hypothesis for the origin of neoplastic
      transformation (mutational genetic, nonmutational genetic, viral, and epigenetic)
      in the context of a summary of our current knowledge of the pathobiology of
      cancer.

PMID- 10201633
TI  - Organ weights and fat volume in rats as a function of strain and age.
AB  - The Fischer 344 (F344) rat and the Sprague-Dawley (SD) rat are used commonly to
      evaluate potential adverse health effects resulting from environmental exposure
      to chemicals. They are also the most common rat strain/stock used in
      physiologically based pharmacokinetic (PBPK) modeling. Accurate characterization
      of model input parameters will improve the usefulness of PBPK model predictions.
      Thus, organ (i.e., liver, kidneys, spleen, stomach, small intestine, large
      intestine, heart, lungs, brain) weights and body fat were measured in male SD
      rats of different ages (4 to 40 wk) and in young (9 to 10 wk) and old (22 to 23
      mo) male F344 rats. Comparison of age-matched (9 to 10 wk) F344 and SD rats
      revealed that the SD rats weighed significantly more and had significantly higher
      absolute organ weights. These significant differences usually disappeared when
      organ weights were expressed as a percentage of body weight (relative organ
      weight). Percent body fat was significantly lower in the age-matched SD rats
      (6.48%) than in their F344 counterparts (8.67%). As expected, both body weight
      and absolute organ weights were significantly higher in old than in young F344
      rats. However, these differences were largely reversed when relative organ
      weights were considered, with most relative organ weights significantly lower in
      the old F344 rats. Body fat as a percentage of body weight was 14.02% in the old
      F344 rats. When SD rats of various ages were examined, relative organ weights
      declined between the ages of 4 and 14 wk. In contrast, significant differences in
      percent body fat were not detected among the SD rats of different ages and
      weights examined in this study (4 to 40 wk, approximately 75 to approximately 450
      g). In summary, values for physiological input parameters are provided that
      should prove useful in development and implementation of more accurate PBPK
      models.

PMID- 10201634
TI  - Effects of kerosene cleaning on the formation of DNA adducts in the skin and lung
      tissues of mice dermally exposed to used gasoline engine oil.
AB  - Used gasoline engine oils (UGEO) are carcinogenic and/or mutagenic in long-term
      studies and capable of increasing the number of mutagen- or carcinogen-DNA
      adducts when applied dermally to mice. The carcinogenic or mutagenic risk of UGEO
      has been attributed to the concentration of polycyclic aromatic compounds (PAC)
      that accumulate in the lubricating system during combustion of gasoline. When
      dermal exposure to UGEO takes place, the use of hand cleansers, solvent- or d
      limonene-based, is commonly recommended for washing, In this study, female mice
      aged 4-6 wk (12-17 g) were utilized to evaluate the efficiency of kerosene, as
      solvent-based cleanser, to remove UGEO following dermal exposure. Using a 32P
      postlabeling technique, the total levels of DNA adducts in skin and lung were
      significantly increased in kerosene-treated mice. Application of UGEO followed by
      kerosene washing significantly decreased skin DNA adduct levels but increased
      lung adduct levels after 8 h. The observed lower DNA adduct skin levels may
      reflect greater UGEO skin penetration and absorption in the presence of kerosene
      cleanser.

PMID- 10201635
TI  - Repeated exposure of rats to JP-4 vapor induces changes in neurobehavioral
      capacity and 5-HT/5-HIAA levels.
AB  - Thirty-two Sprague-Dawley rats were exposed for 6 h/d for 14 consecutive days to
      JP-4 jet fuel vapor (2 mg/L) or room air control conditions. Following a 14- or
      60-d recovery period, rats completed a battery of 8 tests selected from the Navy
      Neurobehavioral Toxicity Assessment Battery (NTAB) to evaluate changes in
      performance capacity. Exposure to JP-4 vapor resulted in significant changes in
      neurobehavioral capacity on several tests that varied as a function of the
      duration of the recovery period. Rats were evaluated for major neurotransmitter
      and metabolite levels in five brain regions and in the blood serum. Levels of 5
      hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were shown to be
      significantly elevated in several brain regions as well as in the blood serum in
      the vapor-exposed groups. Results of the rat study are compared to previously
      reported neurobehavioral evaluations of European manufacturing personnel exposed
      chronically to jet fuel vapor.

PMID- 10201636
TI  - Concentration-dependent absorption of aluminum in rats exposed to labile aluminum
      in drinking water.
AB  - The hypothesis was tested that the absorption of labile Al in rats will increase
      when the Al-binding capacity of food components in the stomach is saturated. Male
      rats were exposed to 0, 10, 50, or 500 mg labile Al/L in acidic drinking water
      (pH 3) for 9 wk. The results show that labile Al in drinking water is complexed
      by feed constituents in the stomach of the rat in vivo, thus causing a
      nondetectable absorption of Al at 10 mg Al/L. An increased absorption of Al at 50
      and 500 mg Al/L was associated with a saturation of the Al-binding capacity of
      feed components in the lumen of the stomach, causing the appearance of labile Al.
      Thus, the presence of labile Al in drinking water does not necessarily result in
      a high Al absorption when the water is ingested, since the bioavailability of
      labile Al is dependent both on the amount and composition of Al-binding
      components present in the gastrointestinal tract at the time of ingestion of the
      water. It is thus not possible to predict the body burden of Al in humans just by
      measuring the Al concentrations in drinking water. Even a further refining of the
      exposure measurement to include speciation of Al in the water may not markedly
      improve the prediction of the Al body burden. Future epidemiological studies must
      therefore be based on actual measurements of Al concentration in tissues or
      fluids from the study subjects.

PMID- 10201637
TI  - Effects of lead on the male reproductive system in mice.
AB  - The effect of environmental lead on the male reproductive system has been a major
      area of concern for several years. Lead toxicity to the male reproductive system
      of sexually mature male CF-1 mice was investigated by administering two
      concentrations of lead (0.25% and 0.5%) via drinking water for 6 wk. The low lead
      dose significantly reduced the number of sperm within the epididymis, while the
      high dose reduced both the sperm count and percentage of motile sperm and
      increased the percentage of abnormal sperm within the epididymis. There was no
      significant effect on testis weight; however, the high-dose treatment
      significantly decreased the epididymis and seminal vesicle weights as well as
      overall body weight gain. Plasma luteinizing hormone (LH), follicle-stimulating
      hormone (FSH), and testosterone (T) levels were not affected by lead
      administration indicating that in adult male CF-1 mice, lead targets testicular
      spermatogenesis and sperm within the epididymis to produce reproductive toxicity
      rather than acting at other sites within the hypothalamic-pituitary-testicular
      axis.

PMID- 10201638
TI  - Glucocorticoid regulation of ornithine decarboxylase in the postnatal rat lung.
AB  - Ornithine decarboxylase (ODC) is thought to play a critical role in pulmonary
      development. The purpose of this study was to characterize the effects of
      dexamethasone on ODC gene expression and enzyme activity in the lung of rat pups.
      Subcutaneous administration of dexamethasone (10 mg/kg) was shown to suppress ODC
      activity in 2-, 6- and 10-day-old rats for as long as 24 h after injection. In
      contrast, dexamethasone treatment stimulated liver ODC activity indicating that
      the inhibition of lung ODC is tissue specific. Contrary to expectation, the
      glucocorticoid enhanced lung ODC expression as indicated by an increased
      accumulation of ODC mRNA transcripts. The latter effect was associated with an
      heightened expression of c-myc and max mRNAs, the encoded proteins of which act
      as transactivators of the ODC gene. Dexamethasone did not alter lung levels
      of"antizyme" (AZ), an inducible protein that specifically promotes the
      degradation of the ODC protein enzyme. However, the lack of AZ induction does not
      necessarily mean that ODC degradation is not the mechanism for the decrease in
      lung ODC activity of dexamethasone-treated animals. The results obtained indicate
      that glucocorticoids can downregulate lung ODC activity, and that the effect is
      mediated by post-transcriptional rather than transcriptional mechanisms. These
      findings are consistent with the idea that endogenous glucocorticoids play an
      important role in the modulation of ODC activity and early pulmonary development.

PMID- 10201639
TI  - Chronic treatment with CP-55,940 regulates corticotropin releasing factor and
      proopiomelanocortin gene expression in the hypothalamus and pituitary gland of
      the rat.
AB  - The purpose of the present study was to explore the molecular mechanisms by which
      the cannabinoid system may interact with the hypothalamic-pituitary adrenal axis
      and the proopiomelanocortin opioid system. To this aim and by using in situ
      hybridization histochemistry, the effects of chronic (18 days) administration
      with the synthetic cannabinoid receptor agonist [(-)-cis-3-[2-hydroxy-4-(1,1,
      dimethylheptyl)-phenyl]-trans-4(-3-h ydroxypropyl)cyclohexanol)], CP-55,940 (1
      mg/kg/day; i.p.) on corticotropin releasing factor and proopiomelanocortin gene
      expression were examined in the paraventricular and arcuate nuclei of the
      hypothalamus and anterior and intermediate lobes of the pituitary gland in the
      rat. Chronic administration with CP-55,940 increased corticotropin releasing
      factor mRNA levels (41%) in the paraventricular nucleus and proopiomelanocortin
      mRNA levels in the arcuate nucleus (25%) and anterior lobe of the pituitary
      (30%), but decreased (28%) of proopiomelanocortin transcript amounts in the
      intermediate lobe of the pituitary. These results revealed that chronic
      cannabinoid administration enhances corticotropin releasing factor and
      proopiomelanocortin gene expression in the hypothalamus and anterior pituitary, a
      process that may be considered as part of a molecular integrative response to the
      stress associated to cannabinoid drug abuse.

PMID- 10201640
TI  - Mu-opioid receptor expression in High Five insect cells is regulated by 5'
      untranslated region (5'UTR).
AB  - There is increasing evidence that the 5'UTR of mRNAs affects regulation of gene
      expression in eukaryotic cells. We examined the overexpression of the mu-opioid
      receptor in High Five insect cells, employing rat mu-receptor cDNA linked to
      variable lenghts of their native 5'UTR. The sequences employed consist of either
      209 nucleotides (termed ,,long") upstream the translation initiation site of the
      mu-receptor mRNA, or a truncated 5'UTR comprising only 11 nucleotides (,,short").
      These constructs served to generate recombinant baculovirus for the expression of
      mu-receptor protein in High Five insect cells. 48 hours after baculovirus
      infection cells were harvested for mu-receptor characterization or RNA analysis.
      Scatchard analysis of radioligand binding consistently revealed three to four
      fold higher concentrations of the mu-opioid receptors expressed with the ,,long"
      over the ,,short" UTR containing baculovirus. The distinct expression rates of mu
      receptors paralleled the amounts of mRNAs determined by RNase protection assay.
      Regardless of the distinct 5'UTR regions, the expressed opioid receptors
      displayed identical high affinity binding characteristics for the opioid
      antagonist diprenorphine and similar EC50 values to inhibit forskolin (10(-5) M)
      stimulated cAMP synthesis. Our results demonstrate that the native 5'UTR of the
      mu-opioid receptor has an enhancing effect on expression in the
      baculovirus/insect cell system.

PMID- 10201641
TI  - Analysis by mass spectrometry of POMC-derived peptides in amphibian melanotrope
      subpopulations.
AB  - We have previously shown that the melanotrope population of the pituitary
      intermediate lobe of Rana ridibunda is composed of two subpopulations, of low
      (LD) and high density (HD), that show distinct ultrastructural features and
      display different synthetic and secretory rates. To investigate whether LD and HD
      melanotrope cells also differ in proopiomelanocortin (POMC) processing, we have
      analyzed the POMC-end products in single cells from both subpopulations by means
      of matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). The
      mass spectra revealed the presence of 8 POMC-derived peptides in HD and LD
      melanotrope cells, indicating a similar processing of the precursor in both
      subpopulations. However, the relative abundance of three POMC-end products (i.e.
      lys-gamma1-MSH, acetyl-alpha-MSH, and CLIP fragment) was higher in the HD subset.
      Moreover, two peptides with molecular weights of 1030 and 1818 Da, respectively,
      were detected that could not be assigned to any product deduced from the frog
      POMC sequence. The relative amount of the 1030 Da peptide was higher in LD
      melanotrope cells. Taken together, our results suggest that POMC processing is
      differentially regulated in the two melanotrope cell subsets.

PMID- 10201642
TI  - The awakening cortisol response and blood glucose levels.
AB  - The hypothalamic-pituitary-adrenal axis is characterized by a marked circadian
      cycle with heightened activity in the morning. This is synchronized to awakening
      such that free cortisol increases two to three fold in the first thirty to forty
      five minutes following awakening -- the awakening cortisol response. It has been
      suggested that this activity, by mobilizing energy reserves prepares the body for
      the metabolic demands of the day. Similar arguments are applied to the cortisol
      response to psychological challenge. Paradoxically the cortisol response to a
      psychosocial stressor is abrogated in fasted individuals with low blood glucose.
      Also cortisol response to a psychosocial stressor is positively correlated to
      blood glucose levels after glucose load. We examined if the same relationship
      applies to the awakening cortisol response. There was no correlation between the
      cortisol response and awakening blood glucose levels. Moreover a group with mean
      blood glucose at the bottom of the euglycemic range, identified by split at the
      median for glucose level upon awakening, showed no deficit in cortisol response.
      Hence the physiology of the awakening response differs to that of a psychological
      stress response. These data challenge the view that an oxidisable substrate for
      energy metabolism is permissive for cortisol responses. In addition the present
      findings do not support a predominantly gluconeogenic role for morning cortisol
      activation.

PMID- 10201643
TI  - Both dopamine and the putative dopamine D3 receptor antagonist PNU-99194A induce
      a biphasic inhibition of phorbol ester-stimulated arachidonic acid release from
      CHO cells transfected with the dopamine D3 receptor.
AB  - In Chinese hamster ovary (CHO) cells transfected with the cDNA for the dopamine
      D3 receptor, low concentrations of dopamine (IC50: 0.5 nM) counteracted the
      release of arachidonic acid (AA) induced by the protein kinase C activator TPA
      (maximal inhibition: 15% at 10 - 30 nM). The effect of dopamine -- which was
      antagonized by pretreatment with pertussis toxin (PTX) or by the dopamine
      receptor antagonist haloperidol -- was biphasic; thus, at increasing
      concentrations of dopamine (100 nM - 1 microM), AA levels approached baseline.
      The preferential dopamine D3 receptor ligand PNU-99194A displayed an effect
      similar to that of dopamine; thus, whereas low concentrations of PNU-99194A
      (IC50: 1.9 nM) reduced TPA-induced AA release (maximal inhibition: 15% at 30 -
      100 nM), higher concentrations (> or =1 microM) were ineffective. When dopamine
      and PNU-99194A were administered together at concentrations yielding maximal
      inhibition of AA release, no additive effect was observed; moreover, a high
      concentration of dopamine counteracted the AA-reducing effect of a low
      concentration of PNU-99194A and vice versa. It is suggested that D3 receptors in
      transfected CHO cells may exert mainly an inhibitory, but also a stimulatory
      influence on TPA-induced AA release, and that PNU-99194A acts as an agonist in
      this system.

PMID- 10201644
TI  - Nitric oxide modulates salivary amylase and fluid, but not epidermal growth
      factor secretion in conscious rats.
AB  - The involvement of the L-arginine/NO pathway in the control of salivary fluid,
      amylase and epidermal growth factor (EGF) secretion was investigated in conscious
      rats. For the collection of saliva, an oesophageal cannula was implanted. To
      obtain steady secretion, submaximal carbachol background infusion was given.
      Different treatments included NO synthase inhibitor N(G)-nitro-L-arginine (NOLA;
      with or without phentolamine, propranolol), L-arginine, D-arginine and NO donor 3
      morpholinosydnonimine (SIN-1) administration. Volume, amylase activity and EGF
      output in the secreted fluid were determined in 30 min mixed saliva samples.
      Carbachol infusion alone produced a modest, sustained salivary fluid and amylase
      secretion. NOLA (30 mg/kg) further increased both fluid (p<0.001) and amylase
      outputs (p<0.001). These latter effects were prevented by L-arginine but not by D
      arginine or by phentolamine. Propranolol administration decreased both fluid and
      amylase secretion below the carbachol plateau, and NOLA did not modify this
      suppressed secretory rate. SIN-1 did not alter either volume or amylase
      secretion. Interestingly, NOLA given without carbachol did not modify salivation.
      Neither carbachol nor NOLA changed salivary EGF output. The present results
      suggest that the L-arginine/NO pathway has a modulatory role in the cholinergic
      control of salivary amylase secretion, but not in EGF output. The mechanisms of
      inhibitory action of NO on salivary fluid and amylase secretion remain to be
      identified.

PMID- 10201645
TI  - Fetal exposure to a maternal low protein diet impairs nephrogenesis and promotes
      hypertension in the rat.
AB  - Epidemiological evidence suggests that hypertension and coronary heart disease
      are programmed by exposure to a poor diet during intrauterine life. It has been
      proposed that the prenatal environment may exert an adverse effect on the
      development of the kidney and hence later control of blood pressure. These
      assertions are supported by animal experiments. In the rat, fetal exposure to a
      maternal low protein diet is associated with disproportionate patterns of fetal
      growth and later elevation of blood pressure. Pregnant female rats were fed
      control (18% casein) or low protein diets throughout pregnancy, or during
      specific periods. Nephron number was determined at day 20 gestation, full term
      and 4 weeks of age. Exposure to low protein throughout gestation, or in mid-late
      gestation increased total nephron number at day 20. By term nephron number was
      reduced, relative to controls, in rats that were undernourished between days 8-14
      or 15-22 gestation. At 4 weeks postnatally rats exposed to low protein throughout
      fetal life had a reduced (13%) nephron complement and blood pressures 13 mmHg
      above control animals. Lower renal size and elevated blood pressure persisted to
      19 weeks of age, at which time glomerular filtration rate was normal. The data
      are consistent with the hypothesis that maternal undernutrition may programme the
      renal nephron number and hence impact upon adult blood pressure and the
      development of renal disease.

PMID- 10201646
TI  - Endogenous catecholamine synthesis, metabolism, storage and uptake in human
      neutrophils.
AB  - Evidence is presented that human neutrophils contain catecholamines and several
      of their metabolites. In vitro, incubation with alpha-methyl-p-tyrosine or
      pargyline affects intracellular dopamine, norepinephrine and their metabolites,
      suggesting catecholamine synthesis and degradation by these cells. Reserpine
      reduces intracellular dopamine and norepinephrine and desipramine reduces
      intracellular norepinephrine, suggesting the presence of storage and uptake
      mechanism. In view of the ability of catecholamines to affect neutrophil
      function, the present results support the hypothesis that autoregulatory
      adrenergic mechanisms may exist in these cells.

PMID- 10201647
TI  - Effects of Y-24180, a receptor antagonist to platelet-activating factor, on
      allergic cutaneous eosinophilia in mice.
AB  - We examined the effects of Y-24180, a potent and long-acting antagonist to
      platelet-activating factor (PAF), on allergic cutaneous eosinophilia and cytokine
      production in the skin of mice. Mice sensitized actively with ovalbumin (OA) were
      challenged by an intradermal injection of OA solution. The number of inflammatory
      cells, including eosinophils and eosinophil peroxidase (EPO) activity reflecting
      eosinophil infiltration into the tissue increased in OA-challenged skin 12 hr
      after the challenge. The levels of interleukin-4 (IL-4) and IL-5 also increased
      significantly in the challenged skin 12 hr and 3-24 hr, respectively, but that of
      interferon-gamma (IFN-gamma) did not change. Then, we evaluated the effects of Y
      24180, ketotifen, suplatast and prednisolone on the increase in EPO activity, IL
      4 and IL-5. These drugs were orally administered once a day for 5 days beginning
      4 days before the challenge. Y-24180 (10 mg/kg) and prednisolone (5 mg/kg)
      significantly suppressed these parameters. Suplatast did not affect EPO activity,
      but significantly decreased the levels of IL-4 and IL-5. Ketotifen had no effect
      on them. These results indicate that the inhibition of IL-4, IL-5 and PAF are
      required to suppress the cutaneous eosinophilia and Y-24180 contributes to the
      treatment of allergic cutaneous eosinophilia.

PMID- 10201648
TI  - Simian virus 40-transformed metallothionein null cells showed increased
      sensitivity to cadmium but not to zinc, copper, mercury or nickel.
AB  - Primary cultured embryonic cells derived from mice with disrupted metallothionein
      (MT) I and II genes and from control mice were transformed with a plasmid
      encoding the simian virus 40 (SV40) large T antigen. The resulting MT-/- and
      MT+/+ cell strains showed similar cell morphology, cell cycle and no significant
      differences in glutathione levels or in the activities of glutathione-related
      enzymes and antioxidant enzymes. The MT-/- cells were more sensitive to Cd than
      MT+/+ cells, though no increase in the sensitivity to Zn, Cu, Hg or Ni were
      observed in MT-/- cells. MT+/+ cells accumulated more Cd than MT-/- cells but
      showed less lesion, suggesting the role of MT induced by Cd in MT+/+ cells as a
      scavenger of toxic Cd ion. These results suggest a dominant protective role of MT
      against Cd compared with other metals. SV40-transformed MT-/- cells seem to be a
      useful tool for the investigation of cellular function of MT.

PMID- 10201649
TI  - Relation of dehydroepiandrosterone and dehydroepiandrosterone sulfate with
      cardiovascular disease risk factors in women: longitudinal results from the
      Massachusetts Women's Health Study.
AB  - Low circulating levels of the adrenal steroids dehydroepiandrosterone (DHEA) and
      dehydroepiandrosterone sulfate (DHEAS) are thought to be associated with
      increased risk of cardiovascular disease (CVD) in men. In women, either a
      positive or null association with CVD has been found. The nature of the relation
      between DHEAS and CVD risk factors in women is unclear and is based on cross
      sectional data. We present results from a longitudinal investigation of serum
      DHEA and DHEAS and cardiovascular disease risk factors in 236 women, initially 50
      60 years old, from a population-based prospective (1986-1995) study of the
      menopausal transition. We used generalized estimating equations to model the
      relation of serum DHEA and DHEAS to systolic and diastolic blood pressure and
      serum levels of total cholesterol, high density lipoprotein cholesterol, and
      apolipoproteins A and B, adjusting for other factors related to CVD. Both DHEA
      and DHEAS were positively related to diastolic and systolic blood pressure, and
      DHEAS was negatively related to apolipoprotein A. DHEA and DHEAS were also
      positively related to smoking, alcohol use, estrone, and estradiol levels, and
      inversely related to age. Our results suggest that higher levels of DHEA and
      DHEAS in middle-aged women may indicate increased CVD risk.

PMID- 10201650
TI  - Clinimetric and psychometric strategies for development of a health measurement
      scale.
AB  - Clinimetrics and psychometrics, two accepted methods for developing multiitem
      health measurement scales, have fundamentally different aims and methods that
      have seldom been compared and never prospectively. The purpose of this study was
      to determine whether these two methodologies provided comparable scales in the
      development of an upper extremity disability measure. Psychometric analysis
      involved field testing a 70-item questionnaire on 407 patients.
      Equidiscriminatory item total correlation (EITC) was used to select the top 30
      items. Clinimetric testing used the mean importance and severity ratings of the
      70 items by 76 patients to select the top 30 items. Clinimetric and psychometric
      analyses were performed independently. Cronbach's alpha was 0.97 for the top 30
      items selected by EITC and 0.96 for the items selected based on patient's
      ratings. The two scales (after clinician modification to improve face validity)
      shared 16 items in common (P=0.10). The intraclass correlation coefficient of the
      patient scores on the two 30-item scales was 0.93 before clinician input and 0.97
      after. The mean (and standard deviation) difference between scales was 9.1 (8.8)
      before and 1.7 (5.2) after clinician input. A scale developed with a clinimetric
      strategy can measure a complex (so-called heterogeneous) clinical phenomenon
      (thought to be composed of several patient attributes) but still fulfill
      psychometric criteria for "homogeneity." Thus, these strategies for the
      development of health measurement scales, which have been considered potentially
      opposite or conflicting, may be complementary.

PMID- 10201651
TI  - Are randomized control trial outcomes influenced by the inclusion of a placebo
      group?: a systematic review of nonsteroidal antiinflammatory drug trials for
      arthritis treatment.
AB  - Placebo groups are often included in randomized control trials evaluating drug
      therapy, yet we know little about the placebo effect. The purpose of our study
      was to evaluate how the presence of a placebo group in a randomized control trial
      (RCT) influences the patients' ratings of the efficacy of an active drug therapy
      and their reporting of its adverse effects. We identified studies published
      between 1966 and 1994 using MEDLINE. Randomized control trials evaluating
      acetylsalicylic acid, diclofenac, or indomethacin for the treatment of osteo or
      rheumatoid arthritis were included in our sample. Two investigators independently
      extracted data. Fifty-eight treatment arms met our inclusion criteria and were
      available for analysis. Twenty-five treatment arms evaluated a nonsteroidal
      antiinflammatory drug (NSAID) in placebo control trials and 33 in comparative
      trials. Using a logistic regression model to adjust for the differences between
      the evaluated drugs and between the types of arthritis, we found that patients
      receiving an NSAID in a placebo control trial were more likely to withdraw due to
      inefficacy (OR=1.3; 95% CI, 1.0 to 1.6; P=0.04). Using a similar model,
      withdrawals due to adverse effects were found to be more common when the NSAID
      was given in trials that did not include a placebo group (OR=1.5; 95% CI, 1.1 to
      1.9; P=0.002) as were reports of cutaneous (OR=4.2; 95% CI, 1.7 to 9.9),
      gastrointestinal (OR=1.6; 95% CI, 1.3 to 2.0), and other types (OR=5.3; 95% CI,
      3.8 to 7.4) of adverse effects. Although reports of central nervous system
      adverse effects were more frequent in the comparative trials, this difference was
      not significant. Including a placebo group in a RCT changes how patients rate the
      efficacy and adverse effects of their therapy. Our results highlight the need to
      consider the placebo effect in the design and analyses of clinical trials.

PMID- 10201652
TI  - A comparison of sensitivity analyses of the effect of wound duration on wound
      healing.
AB  - The effect of an unmeasured exposure on the association between an exposure and
      outcome can never be fully known in an observational study. The purpose of the
      current study was to evaluate the sensitivity to unmeasured confounding of the
      previously published association between wound duration and wound healing in a
      chronic venous leg ulcer. This was estimated using two methods of sensitivity
      analysis, called Rosenbaum's method and Greenland's external adjustment. The
      association between wound duration and wound healing was insensitive to
      confounding unless the odds ratio for the association between the confounder and
      a younger wound was almost nine (Rosenbaum). In fact, the association between
      this hypothetical confounder and healing must have an odds ratio of 100 to remove
      the effect of duration fully (Greenland). Both of these techniques provide useful
      and complementary information when assessing the effects of a potential
      unmeasured confounder.

PMID- 10201653
TI  - Adjusted odds ratios under nondifferential misclassification: application to
      prostate cancer.
AB  - The high prevalence of unsuspected prostate cancer among middle-aged and elderly
      men is unique among cancers. With their uncertain natural history, unsuspected
      prostate cancer cases may be misclassified into control groups in which they can
      obscure the identification of prostate cancer risk factors in case-control
      studies. Assuming that the exposure experience of diagnosed and of unsuspected
      prostate cancers is the same (nondifferential misclassification), case-control
      odds ratios are biased toward the null, which may provide a rationale for
      reexamining findings in negative case-control studies of prostate cancer. This
      article reviews the evidence supporting a high prevalence of prostate cancer and
      describes formulae that can be used to adjust for misclassification bias in
      completed case-control studies and to estimate required sample sizes in proposed
      studies.

PMID- 10201654
TI  - A comparison of the Charlson comorbidity index derived from medical record data
      and administrative billing data.
AB  - The objective of this article is to compare the Charlson comorbidity index
      derived from medical record data (Chart Index) with the same index derived from
      billing data (ICD-9 Index) to determine how well each predicted inpatient and 30
      day mortality, length of stay, and complications among Medicare beneficiaries
      hospitalized for carotid endarterectomy. Economic and time constraints have
      increased the need for risk adjusters derived from administrative data, yet few
      studies have compared these measures with those derived from chart review. Using
      logistic regression, the Chart Index was found to be a significant predictor of
      inpatient mortality, 30-day mortality, length of stay, and complications, after
      controlling for age, gender, and neurologic and medical risk factors (P values =
      0.004, 0.056, 0.0001, and 0.042, respectively). The ICD-9 Index approached
      significance as a predictor of the outcomes (P values = 0.092, 0.100, 0.093, and
      0.080, respectively). The Chart Index was shown to be superior to the ICD-9 Index
      within this patient sample.

PMID- 10201655
TI  - The reliability of medication inventory methods compared to serum levels of
      cardiovascular drugs in the elderly.
AB  - Medication inventory is more reliable than self-report in assessing prescription
      drug use in elderly populations. It is not known how strongly medication
      inventory reflects actual medication use as measured by serum drug levels. In the
      Cardiovascular Health Study, medication data were collected annually by study
      interviewers from medication containers brought to the clinic visit. At the
      fourth clinic visit, venipuncture was performed under 12-hour fasting conditions.
      Participants were told to take medications as usual. Based on medication
      inventory results, we randomly selected 55 users and 55 non-users of four
      cardiovascular drugs: aspirin, propranolol, hydrochlorothiazide, and digoxin. All
      110 blood samples for each of the four drugs were analyzed; cut points were based
      on detectable levels given laboratory limitations. Kappa statistics (K) tested
      degree of agreement between medication inventory findings and serum detection.
      Assays were completed on 400 samples (91%). Agreement for aspirin (n=102) was
      poor: K=0.16 (95% CI: 0.0-0.32). Agreement for propranolol (n = 98) was fair:
      K=0.43 (95% CI: 0.27-0.59). Agreement for hydrochlorothiazide (n=100) was good:
      K=0.62 (95% CI: 0.53-0.91). Agreement for digoxin (n=100) was excellent: K=0.94
      (95% CI: 0.74-1.0). For four all drugs, lack of agreement was confined primarily
      to participants who reported use but did not have detectable levels. Excluding
      aspirin users, only one non-user (0.7%) had drug detected in serum. The
      medication inventory is a reasonably sensitive and a fairly reliable method for
      ascertaining non-aspirin cardiovascular drug use in the elderly even though this
      method may overestimate use as assessed by serum level.

PMID- 10201656
TI  - Identifying providers of care to individuals with human immunodeficiency virus
      for a mail survey using a prescription tracking database.
AB  - Unlike cancer and other illnesses for which specialists provide the majority of
      care for affected individuals, care of those infected with human immunodeficiency
      virus (HIV) is provided by generalists and many different types of specialists.
      To assess the utility of a prescription tracking database in identifying low
      experience and high-experience providers of such care regardless of specialty, we
      mailed a survey to 1500 physicians identified as having written prescriptions for
      agents used in care of HIV-infected individuals in the year before the survey. We
      discovered that physicians who care for patients with acquired immunodeficiency
      syndrome (AIDS) in the United States come from a broad range of specialties and
      practice in a variety of settings. Self-report of experience with AIDS care in
      the prior year was strongly associated with the number of HIV-related
      prescriptions identified in the tracking information. Response rates were
      consistent with those of other surveys published in medical journals. This study
      suggests that prescription tracking databases can be used to identify the breadth
      of physician/subjects who provide care for patients with HIV infection.

PMID- 10201657
TI  - Comparison between planned and unplanned readmissions to a department of internal
      medicine.
AB  - The objective of this study was to assess the respective frequency of planned and
      unplanned early readmissions after discharge from an internal medicine
      department, and to identify and compare risk factors for these two types of
      readmissions. Readmissions within 31 days of discharge were identified as planned
      or unplanned based on analysis of discharge summaries. Time-failure methods were
      used to describe the risk of readmissions over time and to assess relationships
      between patient and index stay characteristics and risk of readmission. Of 5828
      patients discharged alive, 730 (12.5%) were readmitted within 31 days. There were
      slightly more planned than unplanned readmissions (393 vs. 337). The difference
      in time-to-event functions was significant (P=0.04). The risk of planned
      readmission was increased for men, younger patients, and for patients discharged
      with a diagnosis of coronary heart disease, cardiac arrhythmia, and neoplastic
      disease. Increased risk of unplanned readmission was associated with index length
      of stay longer than 3 days, an increased number of comorbidities, and with a
      diagnosis of neoplastic disease. Planned readmissions constitute more than half
      of early readmissions to our internal medicine department. Therefore, a crude
      readmission rate is unlikely to be a useful indicator of quality of care. Several
      patient characteristics influence the risk of unplanned readmission, suggesting
      that case-mix adjustments are necessary when readmission rates are compared
      between institutions or tracked over time.

PMID- 10201658
TI  - The validity of the routine mortality statistics on coronary heart disease in
      Finland: comparison with the FINMONICA MI register data for the years 1983-1992.
      Finnish multinational MONItoring of trends and determinants in CArdiovascular
      disease.
AB  - We compared the diagnoses obtained from the routine mortality statistics with the
      standardized World Health Organization (WHO) MONICA (multinational MONItoring of
      trends and determinants in CArdiovascular disease) classification in suspect
      coronary heart disease (CHD) deaths registered in the FINMONICA myocardial
      infarction (MI) register during 1983-1992. All CHD deaths from routine mortality
      statistics (International Classification of Diseases codes 410-414) were
      registered in the MI register. Of the CHD deaths in routine mortality statistics
      1.7% in men and 4.8% in women did not fulfill the MONICA criteria for CHD death
      (P<0.001 for the difference between the sexes). In men 4.7% and in women 7.3%
      (P=0.004) of the deaths registered in the MI Register and classified as CHD
      deaths by MONICA criteria had another underlying cause of death than CHD in
      routine mortality statistics; this proportion increased over time in both sexes
      (P=0.002 in men and P=0.77 in women). The CHD mortality trends obtained
      separately from the routine mortality statistics and from the FINMONICA MI
      Register were very similar. In conclusion, the high CHD mortality in Finland
      reported by the routine mortality statistics is real. It is possible that some
      CHD deaths have escaped registration, but the decline seen in the CHD mortality
      is also real.

PMID- 10201659
TI  - Lipid-lowering medication and risk of cancer.
AB  - Low or declining levels of serum cholesterol have been associated with increased
      mortality from cancer. We conducted a population-based cohort study of 1882
      patients from one Danish county who received lipid-lowering drugs between January
      1, 1991 and December 31, 1994. During the follow-up period of up to 4 years, 41
      cancers were observed among users of lipid-lowering drugs, with 42.9 expected, to
      yield an age- and sex-standardized incidence ratio of 1.0 (95% confidence
      interval, 0.7-1.3). Although limited by small numbers and short follow-up period,
      examination by site of cancer and type of drug provided no evidence of an
      association. Further research is needed, however, with longer follow-up to assess
      more fully any potential cancer risk with these medications.

PMID- 10201660
TI  - Is ropivacaine less potent than bupivacaine?

PMID- 10201661
TI  - Relative analgesic potencies of ropivacaine and bupivacaine for epidural
      analgesia in labor: implications for therapeutic indexes.
AB  - BACKGROUND: The minimum local analgesic concentration (MLAC) has been defined as
      the median effective local analgesic concentration in a 20-ml volume for epidural
      analgesia in the first stage of labor. The aim of this study was to assess the
      relative analgesic potencies of epidural bupivacaine and ropivacaine by
      determining their respective minimum local analgesic concentrations. METHODS:
      Seventy-three parturients at < or = 7 cm cervical dilation who requested epidural
      analgesia were allocated to one of two groups in this double-blinded, randomized,
      prospective study. After a lumbar epidural catheter was placed, 20 ml of the test
      solution was given, either ropivacaine (n = 34) or bupivacaine (n = 39). The
      concentration of local anesthetic was determined by the response of the previous
      patient in that group to a higher or lower concentration using up-down sequential
      allocation. Analgesic efficacy was assessed using 100-mm visual analog pain
      scores with < or = 10 mm within 30 min defined as effective. An effective result
      directed a 0.01% wt/vol decrement for the next patient. An ineffective result
      directed a 0.01% wt/vol increment. RESULTS: The minimum local analgesic
      concentration of ropivacaine was 0.111% wt/vol (95% confidence interval, 0.100
      0.122), and the minimum local analgesic concentration of bupivacaine was 0.067%
      wt/vol (95% confidence interval, 0.052-0.082). Ropivacaine was significantly less
      potent than bupivacaine, with a potency ratio of 0.6 (95% confidence interval,
      0.49-0.74). No difference in motor effects was observed. CONCLUSION: Ropivacaine
      was significantly less potent than bupivacaine for epidural analgesia in the
      first stage of labor.

PMID- 10201662
TI  - Effects of an intubating dose of succinylcholine and rocuronium on the larynx and
      diaphragm: an electromyographic study in humans.
AB  - BACKGROUND: Paralysis of the vocal cords is one objective of using relaxants to
      facilitate tracheal intubation. This study compares the neuromuscular blocking
      effect of succinylcholine and rocuronium on the larynx, the diaphragm, and the
      adductor pollicis muscle. METHODS: Electromyographic response was used to compare
      the neuromuscular blocking effect of succinylcholine and rocuronium on the
      laryngeal adductor muscles, the diaphragm, and the adductor pollicis muscle.
      Sixteen patients undergoing elective surgery were anesthetized with propofol and
      fentanyl, and their tracheas were intubated without neuromuscular blocking
      agents. The recurrent laryngeal and phrenic nerves were stimulated at the neck.
      The electromyographic response was recorded from electrodes placed on the
      endotracheal tube and intercostally before and after administration of 1 mg/kg
      succinylcholine or 0.6 mg/kg rocuronium. RESULTS: The maximum effect was greater
      at the adductor pollicis (100 and 99%) than at the larynx (96 and 97%) and the
      diaphragm (94 and 96%) after administration of succinylcholine and rocuronium,
      respectively (P < or = 0.05). Onset time was not different between the larynx
      (58+/-10 s), the diaphragm (57+/-8 s), and the adductor pollicis (54+/-13 s),
      after succinylcholine (all mean +/- SD). After rocuronium, onset time was 124+/
      39 s at the larynx, 130+/-44 s at the diaphragm, and 115+/-21 s at the adductor
      pollicis. After succinylcholine administration, time to 90% recovery was 8.3+/
      3.2, 7.2+/-3.5, and 9.1+/-3.0 min at the larynx, the diaphragm, and the adductor
      pollicis, respectively. Time to 90% recovery after rocuronium administration was
      34.9+/-7.6, 30.4+/-4.2, and 49.1+/-11.4 min at the larynx, the diaphragm, and the
      adductor pollicis, respectively. CONCLUSION: Neuromuscular blocking effect of
      muscle relaxants on the larynx can be measured noninvasively by electromyography.
      Although the larynx appears to be resistant to muscle relaxants, we could not
      demonstrate that its onset time differed from that of peripheral muscles.

PMID- 10201663
TI  - Comparison of adenosine and remifentanil infusions as adjuvants to desflurane
      anesthesia.
AB  - BACKGROUND: Because adenosine has been alleged to produce both anesthetic and
      analgesic sparing effects, a randomized, double-blinded study was designed to
      compare the perioperative effects of adenosine and remifentanil when administered
      as intravenous adjuvants during general anesthesia for major gynecologic
      procedures. METHODS: Thirty-two women were assigned randomly to one of two drug
      treatment groups. After premedication with 0.04 mg/kg intravenous midazolam,
      anesthesia was induced with 2 micro/kg intravenous fentanyl, 1.5 mg/kg
      intravenous propofol, and 0.6 mg/kg intravenous rocuronium, and maintained with
      desflurane, 2%, and nitrous oxide, 65%, in oxygen. Before skin incision, an
      infusion of either remifentanil (0.02 microg x kg(-1) x min(-1)) or adenosine (25
      microg x kg(-1) x min(-1)) was started and subsequently titrated to maintain
      systolic blood pressure, heart rate, or both within 10-15% of the preincision
      values. RESULTS: Adenosine and remifentanil infusions were effective anesthetic
      adjuvants during lower abdominal surgery. Use of adenosine (mean +/- SEM, 166+/
      17 microg x kg(-1) x min(-1)) was associated with a significantly greater
      decrease in systolic blood pressure and higher heart rate values compared with
      remifentanil (mean +/- SEM, 0.2+/-0.03 microg kg(-1) x min(-1)). Total
      postoperative opioid analgesic use was 45% and 27% lower in the adenosine group
      at 0-2 h and 2-24 h after surgery, respectively. CONCLUSIONS: Adjunctive use of a
      variable-rate infusion of adenosine during desflurane-nitrous oxide anesthesia
      was associated with acceptable hemodynamic stability during the intraoperative
      period. Compared with remifentanil, intraoperative use of adenosine was
      associated with a decreased requirement for opioid analgesics during the first 24
      h after operation.

PMID- 10201664
TI  - Epidural catheter tip position and distribution of injectate evaluated by
      computed tomography.
AB  - BACKGROUND: The distribution of solutions injected into the epidural space has
      not been determined. The author therefore examined the site of catheter tips and
      the spread of contrast material in the epidural space using computed tomographic
      (CT) imaging in patients receiving successful epidural analgesia. METHODS: Lumbar
      epidural catheters were placed in 20 female patients by a midline technique.
      Anesthetic effect was determined by motor and sensory examinations during
      analgesic infusion. CT images were obtained for identification of the catheter
      tip and after radiographic contrast injection of 4 ml and then an additional 10
      ml. RESULTS: Catheter tips were most often found lateral to the dura in the
      intervertebral foramen. In these subjects with normally functioning epidural
      analgesia, there was remarkable interindividual variability in patterns of
      spread, including various amounts of anterior passage, layering along the dura,
      and compression of the dura creating a posterior fold. Accumulation becomes more
      symmetric with increasing injectate volume. Spread through the intervertebral
      foramina was seen in all subjects. Air and fat in the region of the catheter
      interfered with solution spread in three subjects, but only over a limited area.
      Asymmetry in anesthetic effect was attributable to catheter position. No
      substantial barriers to solution spread were observed. CONCLUSIONS: A variety of
      catheter tip positions and patterns of solution spread underlie normal epidural
      anesthesia. Nonuniform distribution of injectate is common and is compatible with
      uniform anesthesia. Posterior midline structures play a minimal role in impeding
      distribution of injectate. A far lateral catheter position is a more common cause
      of asymmetric block than anatomic barriers to solution spread.

PMID- 10201665
TI  - Hyperbaric spinal ropivacaine: a comparison to bupivacaine in volunteers.
AB  - BACKGROUND: Ropivacaine is a newly introduced local anesthetic that may be a
      useful alternative to low-dose bupivacaine for outpatient spinal anesthesia.
      However, its relative potency to bupivacaine and its dose-response
      characteristics are unknown. This double-blind, randomized, crossover study was
      designed to determine relative potencies of low-dose hyperbaric spinal
      ropivacaine and bupivacaine and to assess the suitability of spinal ropivacaine
      for outpatient anesthesia. METHODS: Eighteen healthy volunteers were randomized
      into three equal groups to receive one spinal administration with bupivacaine and
      a second with ropivacaine, of equal-milligram doses (4, 8, or 12 mg) of 0.25%
      drug with 5% dextrose. The duration of blockade was assessed with (1) pinprick,
      (2) transcutaneous electrical stimulation, (3) tolerance to high tourniquet, (4)
      electromyography and isometric force dynamometry, and (5) achievement of
      discharge criteria. Differences between ropivacaine and bupivacaine were assessed
      with linear and multiple regression. P < 0.05 was considered significant.
      RESULTS: Ropivacaine and bupivacaine provided dose-dependent prolongation of
      sensory and motor block and time until achievement of discharge criteria (R2
      ranges from 0.33-0.99; P values from < 0.001 through 0.01). Spinal anesthesia
      with ropivacaine was significantly different from bupivacaine and was
      approximately half as potent for all criteria studied. A high incidence of back
      pain (28%; P = 0.098) was noted after intrathecal ropivacaine was given.
      CONCLUSION: Ropivacaine is half as potent and in equipotent doses has a similar
      profile to bupivacaine with a higher incidence of side effects. Low-dose
      hyperbaric spinal ropivacaine does not appear to offer an advantage over
      bupivacaine for use in outpatient anesthesia.

PMID- 10201666
TI  - Preoperative fasting practices in pediatrics.
AB  - BACKGROUND: The purpose of this study was to determine current practice patterns
      for preoperative fasting at major pediatric hospitals. METHODS: Fasting
      guidelines for children at each of the hospitals listed in the second edition of
      the Directory of Pediatric Anesthesiology Fellowship Programs were solicited and
      analyzed. RESULTS: Fifty-one institutions were surveyed, and 44 responded. In
      50%, clear fluids were permitted up to 2 h prior to anesthesia for all children.
      Breast milk was restricted to 4 h for children younger than 6 months in 61% of
      hospitals. Institutions were equally divided (39% each) between a 4-h and a 6-h
      fast for formula in infants younger than 6 months; for infants older than 6
      months, 50% of hospitals restricted formula feeding to 6 h. There was no
      consensus for solid feeding in children younger than 3 yr, but 50% of hospitals
      agree that solids should be restricted after midnight in children older than 3
      yr. CONCLUSIONS: There is no uniform fasting practice for children before
      elective surgery in the United States and Canada. However, there is agreement
      among most institutions that ingestion of clear fluids 2-3 h prior to general
      anesthesia is acceptable. Most also accept a 4-h restriction for breast milk and
      a 6-h restriction for nonhuman formula. There is great diversity among
      institutions regarding fasting for solids in children, with many restricting
      intake after midnight. There is little agreement about whether infant formula
      should be treated in the same way as solid food or how to categorize breast milk.

PMID- 10201667
TI  - Dose response of intravenous heparin on markers of thrombosis during primary
      total hip replacement.
AB  - BACKGROUND: Thrombogenesis in total hip replacement (THR) begins during surgery
      on the femur. This study assesses the effect of two doses of unfractionated
      intravenous heparin administered before femoral preparation during THR on
      circulating markers of thrombosis. METHODS: Seventy-five patients undergoing
      hybrid primary THR were randomly assigned to receive blinded intravenous
      injection of either saline or 10 or 20 U/kg of unfractionated heparin after
      insertion of the acetabular component. Central venous blood samples were assayed
      for prothrombin F1+2 (F1+2), thrombin-antithrombin complexes (TAT),
      fibrinopeptide A (FPA), and D-dimer. RESULTS: No changes in the markers of
      thrombosis were noted after insertion of the acetabular component. During surgery
      on the femur, significant increases in all markers were noted in the saline group
      (P < 0.0001). Heparin did not affect D-dimer or TAT. Twenty units per kilogram of
      heparin significantly reduced the increase of F1+2 after relocation of the hip
      joint (P < 0.001). Administration of both 10 and 20 U/kg significantly reduced
      the increase in FPA during implantation of the femoral component (P < 0.0001). A
      fourfold increase in FPA was noted in 6 of 25 patients receiving 10 U/kg of
      heparin but in none receiving 20 U/kg (P = 0.03). Intraoperative heparin did not
      affect intra- or postoperative blood loss, postoperative hematocrit, or surgeon's
      subjective assessments of bleeding. No bleeding complications were noted.
      CONCLUSIONS: This study demonstrates that 20 U/kg of heparin administered before
      surgery on the femur suppresses fibrin formation during primary THR. This finding
      provides the pathophysiologic basis for the clinical use of intraoperative
      heparin during THR.

PMID- 10201668
TI  - Pharmacokinetics of prilocaine after intravenous administration in volunteers:
      enantioselectivity.
AB  - BACKGROUND: Prilocaine exists in two stereoisomeric configurations, the
      enantiomers S(+)- and R(-)-prilocaine. The drug is clinically used as the
      racemate. This study examined the pharmacokinetics of the enantiomers after
      intravenous administration of the racemate. METHODS: Ten healthy male volunteers
      received 200 mg racemic prilocaine as a 10-min intravenous infusion. Blood
      samples were collected for 8 h after the start of the infusion. Plasma
      concentrations were measured by stereoselective high-performance liquid
      chromatography (HPLC). Unbound fractions of the enantiomers in blank blood
      samples, spiked with racemic prilocaine, were determined using equilibrium
      dialysis. RESULTS: The unbound fraction of R(-)-prilocaine (mean +/- SD, 70%+/
      8%) was smaller (P < 0.05) than that of S(+)-prilocaine (73%+/-5%). The total
      plasma clearance of R(-)-prilocaine (2.57+/-0.46 l/min) was larger (P < 0.0001)
      than that of S(+)-prilocaine (1.91+/-0.30 l/min). The steady-state volume of
      distribution of R(-)-prilocaine (279+/-94 l) did not differ from that of S(+)
      prilocaine (291+/-93 l). The terminal half-life of R(-)-prilocaine (87+/-27 min)
      was shorter (P < 0.05) than that of S(+)-prilocaine (124+/-64 min), as was the
      mean residence time of R(-)-prilocaine (108+/-30 min) compared with S(+)
      prilocaine (155+/-59 min; P < 0.005). CONCLUSIONS: The pharmacokinetics of
      prilocaine are enantioselective. The difference in clearance is most likely a
      result of a difference in intrinsic metabolic clearance. The difference in the
      pharmacokinetics of the enantiomers of prilocaine does not seem to be clinically
      relevant.

PMID- 10201669
TI  - Factors affecting the pharmacokinetic characteristics of rapacuronium.
AB  - BACKGROUND: Rapacuronium is a new nondepolarizing muscle relaxant with rapid
      onset and offset. As part of a study to determine its neuromuscular effects, the
      authors sampled plasma sparsely to determine the influence of age, gender, and
      other covariates on its pharmacokinetic characteristics. METHODS: Of 181 patients
      receiving a single bolus dose of 0.5-2.5 mg/kg rapacuronium, 43 (aged 24-83 yr)
      had plasma sampled 3 or 4 times to determine plasma concentrations of
      rapacuronium and its metabolite, ORG9488. Pharmacokinetic analysis was performed
      using a population approach (mixed-effects modeling) to determine the influence
      of demographic characteristics and preoperative laboratory values on the
      pharmacokinetic parameters. RESULTS: Rapacuronium's weight-normalized plasma
      clearance was 7.03 x (1 - 0.0507 x (HgB - 13)) ml x kg(-1) x min(-1), where HgB
      is the patient's preoperative value for hemoglobin (g/100 ml); however,
      rapacuronium's blood clearance (11.4+/-1.4 ml x kg(-1) x min(-1), mean +/- SD)
      did not vary with hemoglobin. Rapacuronium's weight-normalized pharmacokinetic
      parameters were not influenced by age, gender, or other covariates examined.
      Plasma concentrations of ORG9488 were typically less than 14% those of
      rapacuronium during the initial 30 min after rapacuronium administration.
      CONCLUSIONS: In this patient population, neither age nor gender influence
      elimination of rapacuronium. This finding contrasts to an age-related decrease in
      plasma clearance observed in a study of 10 healthy volunteers and in a pooled
      analysis of the pharmacokinetic data from 206 adults in multiple clinical
      studies. Even if ORG9488 has a potency similar to that of rapacuronium, its
      plasma concentrations after a single bolus dose of rapacuronium are sufficiently
      small to contribute minimally to neuromuscular blockade.

PMID- 10201670
TI  - Pharyngeal mucosal pressures, airway sealing pressures, and fiberoptic position
      with the intubating versus the standard laryngeal mask airway.
AB  - BACKGROUND: The tube of the intubating laryngeal mask (ILM) is more rigid than
      the standard laryngeal mask airway (LMA), and the authors have tested the
      hypothesis that pharyngeal mucosal pressures, airway sealing pressures, and
      fiberoptic position are different when the two devices are compared. METHODS:
      Twenty anesthetized, paralyzed adults were randomly allocated to receive either
      the LMA or ILM for airway management. Microchip sensors were attached to the size
      5 LMA or ILM at locations corresponding to the pyriform fossa, hypopharynx, base
      of tongue, posterior pharynx, and distal and proximal oropharynx. Mucosal
      pressures, airway sealing pressures, and fiberoptic positioning were recorded
      during inflation of the cuff from 0 to 40 ml in 10-ml increments. RESULTS: Airway
      sealing pressures were higher for the ILM (30 vs. 23 cm H2O), but epiglottic
      downfolding was more common (56% vs. 26%). Pharyngeal mucosal pressures were much
      higher for the ILM at five of six locations. Mean mucosal pressures in the distal
      oropharynx for the ILM were always greater than 157 cm H2O, regardless of cuff
      volume. There was no correlation between mucosal pressures and airway sealing
      pressures at any location for the LMA, but there was a correlation at three of
      six locations for the ILM. CONCLUSIONS: The ILM provides a more effective seal
      than the LMA, but pharyngeal mucosal pressures are higher and always exceed
      capillary perfusion pressure. The ILM is unsuitable for use as a routine airway
      and should be removed after its use as an airway intubator.

PMID- 10201671
TI  - Effects of prophylactic nalmefene on the incidence of morphine-related side
      effects in patients receiving intravenous patient-controlled analgesia.
AB  - BACKGROUND: Opioid-related side effects associated with intravenous patient
      controlled analgesia can be reduced by a low-dose naloxone infusion. The
      influence of nalmefene, a pure opioid antagonist with a longer duration of
      action, on opioid-related side effects has not been evaluated. This study was
      designed to determine the dose-response relation for nalmefene for the prevention
      of morphine-related side effects in patients receiving intravenous patient
      controlled analgesia. METHODS: One hundred twenty women undergoing lower
      abdominal surgery were enrolled in the study. General anesthesia was induced
      using thiopental and rocuronium and maintained with desflurane, nitrous oxide,
      and fentanyl or sufentanil. All patients received neostigmine and glycopyrrolate
      to reverse residual neuromuscular blockade. No prophylactic antiemetics were
      administered. At the end of surgery, patients were randomized to receive saline,
      15 microg nalmefene, or 25 microg nalmefene intravenously. The need for
      antiemetic and antipruritic drugs and the total consumption of morphine during
      the 24-h study were recorded. The incidences of postoperative nausea, vomiting,
      pruritus, and pain were recorded 30 min after patients were admitted to the
      postanesthesia care unit. In addition, patient remembrance of these side effects
      was noted at 24 h after operation. RESULTS: The need for antiemetic and
      antipruritic medications during the 24-h study period was significantly lower in
      the patients receiving nahmefene compared with those receiving placebo. However,
      the need to treat side effects was similar in the two nahmefene groups.
      Prophylactic administration of nalmefene reduced the patients remembrance of
      nausea and itching as assessed 24 h after operation. Although the total
      consumption of morphine during the 24-h study period was similar in the three
      groups, retrospectively patients who received nalmefene characterized their pain
      as less severe in the previous 24 h. CONCLUSION: Compared with placebo,
      prophylactic administration of nalmefene significantly decreased the need for
      antiemetics and antipruritic medications in patients receiving intravenous
      patient-controlled analgesia with morphine.

PMID- 10201672
TI  - The pharmacokinetics of milrinone in pediatric patients after cardiac surgery.
AB  - BACKGROUND: Milrinone has been shown to increase cardiac output in children after
      cardiac surgery, but pharmacokinetic analysis has not been used to identify
      effective dose regimens. The purpose of this study was to characterize the
      pharmacokinetics of milrinone in infants and children and to apply the results to
      the issue of dosing. METHODS: Twenty children were studied after they underwent
      repair of congenital cardiac defects. Control hemodynamic measurement was made
      after the children were separated from cardiopulmonary bypass, and each patient
      was given a loading dose of 50 microg/kg progressively in 5 min. Hemodynamic
      measurements were recorded again at the end of the loading dose and when a blood
      sample was taken to determine milrinone plasma concentrations. Further blood
      samples were taken during the next 16 h for milrinone plasma concentration
      analysis. The pharmacokinetics of milrinone were analyzed using the population
      pharmacokinetic program NONMEM. RESULTS: The loading dose of milrinone resulted
      in a mean decrease in mean blood pressure of 12% and a mean increase in cardiac
      index of 18% at a mean peak plasma concentration of 235 ng/ml. The
      pharmacokinetics of milrinone were best described by a three-compartment model.
      In the optimal model, all volumes and distribution clearances were proportional
      to weight, and weight-normalized elimination clearance was proportional to age;
      ie., Cl1 = 2.5 x weight x (1 + 0.058 x age) where Cl1 is expressed as ml/min, and
      the units of weight and age are kg and months, respectively. CONCLUSIONS: A
      loading dose of 50 microg/kg effectively increases cardiac index in children
      after cardiac surgery. Simulations indicate that the peak plasma concentration
      can be maintained by following the loading dose of 50 microg/kg with an infusion
      of approximately 3 microg x kg(-1) x min(-1) for 30 min and then a maintenance
      infusion, which may require adjustment for age.

PMID- 10201673
TI  - Halothane induces calcium release from human skinned masseter muscle fibers.
AB  - BACKGROUND: An increase in masseter muscle tone in response to halothane or
      succinylcholine anesthesia (or both) can be observed in healthy persons. Thus the
      authors compared the fiber-type halothane and succinylcholine sensitivities in
      human masseter and vastus lateralis muscles. METHODS: Masseter and vastus
      lateralis muscle segments were obtained from 13 and 9 healthy persons,
      respectively. After chemical skinning of a single fiber and loading the
      sarcoplasmic reticulum with Ca++ 0.16 microM solution, halothane (0.5-4 vol%
      bubbled in the incubating solution), succinylcholine (0.1 microM to 10 mM), or
      both sensitivities were defined as the concentration inducing more than 10% of
      the maximum tension obtained by application of 16 microM Ca++ solution. The
      myofilament response to Ca++ was studied with and without halothane by observing
      the isometric tension of skinned masseter fibers challenged with increasing
      concentrations of Ca++. Muscle fiber type was determined by the difference in
      strontium-induced tension measurements. RESULTS: A significant difference in
      halothane sensitivity was found between type 1 masseter fibers (0.6+/-0.2 vol%;
      mean +/- SD) versus type 1 (2.7+/-0.6 vol%) and type 2 vastus lateralis muscle
      (2.5+/-0.4 vol%). Succinylcholine did not induce Ca++ release by the sarcoplasmic
      reticulum. In the masseter muscle, 0.75 vol% halothane decreased the maximal
      activated tension by 40% but did not change the Ca++ concentration that yields
      50% of the maximal tension. CONCLUSIONS: The very low halothane threshold for
      Ca++ release from the masseter muscle usually could be counteracted by a direct
      negative inotropic effect on contractile proteins. However, halothane may
      increase the sensitivity of the sarcoplasmic reticulum Ca++ release to
      succinylcholine-induced depolarization, leading to an increase in masseter muscle
      tone.

PMID- 10201674
TI  - Pharmacokinetic modeling of M6G formation after oral administration of morphine
      in healthy volunteers.
AB  - BACKGROUND: Morphine is metabolized to two major metabolites, morphine-3
      glucuronide and morphine-6-glucuronide (M6G). Under the conditions of long-term
      oral morphine administration, the accumulation of M6G may contribute to the
      analgesic effects, but it may also cause respiratory depression. METHODS: Five
      healthy male volunteers (ages 25-34 yr) received 90 mg MST (morphine sulfate 5H2O
      sustained-released tablet, equivalent to 67.8 mg oral morphine). Multiple plasma
      and urine samples were taken for as long as 14 and 36 h, respectively. Individual
      pharmacokinetics after intravenous administration of morphine and M6G were
      available from a previous investigation. A new model that considers the M6G
      plasma profile as a sum of the input from the first-pass metabolism of morphine
      and the input from systemically available morphine was applied to the plasma
      concentration versus time curves of M6G. The concentrations of M6G at the effect
      site after long-term morphine administration were simulated. RESULTS: The
      fraction of morphine absorbed from the gut was 82+/-14%. Of this, 42+/-8% passed
      through the liver, resulting in an oral bioavailability of morphine of 34+/-9%.
      Of the total amount of M6G, 71+/-7% was formed during the first-pass metabolism,
      and 29+/-7% was formed by metabolism of systemic morphine. After 36 h, the
      amounts of M6G and morphine excreted in the urine were 92+/-17% and 9+/-3%,
      respectively. Simulation of effect-site concentrations of M6G indicated that
      after multiple oral dosing of morphine in patients with normal liver and renal
      function, M6G might reach concentrations two times greater than that of morphine.
      CONCLUSIONS: M6G may contribute to the analgesic and side effects seen with long
      term morphine treatment. The current model of morphine and M6G pharmacokinetics
      after oral administration of morphine may serve as a pharmacokinetic basis for
      experiments evaluating the analgesic contribution of M6G with long-term oral
      dosing of morphine.

PMID- 10201675
TI  - Lumbar sympathetic blocks speed early and second stage induced labor in
      nulliparous women.
AB  - BACKGROUND: Rapid cervical dilation reportedly accompanies lumbar sympathetic
      blockade, whereas epidural analgesia is associated with slow labor. The authors
      compared the effects of initial lumbar sympathetic block with those of epidural
      analgesia on labor speed and delivery mode in this pilot study. METHODS: At a
      hospital not practicing active labor management, full-term nulliparous patients
      whose labors were induced randomly received initial lumbar sympathetic block or
      epidural analgesia. The latter patients received 10 ml bupivacaine, 0.125%; 50
      microg fentanyl; and 100 microg epinephrine epidurally and sham lumbar
      sympathetic blocks. Patients to have lumbar sympathetic blocks received 10 ml
      bupivacaine, 0.5%; 25 microg fentanyl; and 50 microg epinephrine bilaterally and
      epidural catheters. Subsequently, all patients received epidural analgesia.
      RESULTS: Cervical dilation occurred more quickly (57 vs. 120 min/cm cervical
      dilation; P = 0.05) during the first 2 h of analgesia in patients having lumbar
      sympathetic blocks (n = 17) than in patients having epidurals (n = 19). The
      second stage of labor was briefer in patients having lumbar sympathetic blocks
      than in those having epidurals (105 vs. 270 min; P < 0.05). Nine patients having
      lumbar sympathetic block and seven having epidurals delivered spontaneously,
      whereas seven patients having lumbar sympathetic block and seven having epidurals
      had instrument-assisted vaginal deliveries. Cesarean delivery for fetal
      bradycardia occurred in one patient having lumbar sympathetic block. Cesarean
      delivery for dystocia occurred in five patients having epidurals compared with no
      patient having lumbar sympathetic block (P = not significant). Visual analog pain
      scores differed only at 60 min after block. CONCLUSIONS: Nulliparous parturients
      having induced labor and receiving initial lumbar sympathetic blocks had faster
      cervical dilation during the first 2 h of analgesia, shorter second-stage labors,
      and a trend toward a lower dystocia cesarean delivery rate than did patients
      having epidural analgesia. The effects of lumbar sympathetic block on labor need
      to be determined in other patient groups. These results may help define the
      tocodynamic effects of regional labor analgesia.

PMID- 10201676
TI  - Ropivacaine or 2% mepivacaine for lower limb peripheral nerve blocks. Study Group
      on Orthopedic Anesthesia of the Italian Society of Anesthesia, Analgesia, and
      Intensive Care.
AB  - BACKGROUND: Intra- and postoperative clinical properties of sciatic-femoral nerve
      block performed with either ropivacaine at different concentrations or
      mepivacaine have been evaluated in a multicenter, randomized, blinded study.
      METHODS: Adult patients scheduled for foot and ankle surgery were randomized to
      receive combined sciatic-femoral nerve block with 225 mg of either 0.5% (n = 83),
      0.75% (n = 87), or 1% (n = 86) ropivacaine, or with 500 mg of 2% mepivacaine (n =
      84). A thigh tourniquet was used in all patients. Onset time, adequacy of
      surgical anesthesia, time to offset of nerve block, and time until first
      postoperative requirement for pain medication were evaluated by a blinded
      observer. RESULTS: The adequacy of nerve block was similar in the four treatment
      groups (the ratios between adequate:inadequate: failed blocks were 74:9:0 with
      0.5% ropivacaine, 74:13:0 with 0.75% ropivacaine, 78:8:0 with 1% ropivacaine, and
      72:12:0 with 2% mepivacaine). The onset of the block was slower with 0.5%
      ropivacaine than with other anesthetic solutions (P < 0.001). Regardless of the
      concentration, ropivacaine produced a longer motor blockade (10.5+/-3.8 h, 10.3+/
      4.3 h, and 10.2+/-5.1 h with 0.5%, 0.75%, and 1% ropivacaine, respectively) than
      with mepivacaine (4.3+/-2.6 h; P < 0.001). The duration of postoperative
      analgesia was shorter after mepivacaine (5.1+/-2.7 h) than after ropivacaine
      (12.2+/-4.1 h, 14.3+/-5 h, and 14.5+/-3.4 h, with 0.5%, 0.75%, or 1% ropivacaine,
      respectively; P < 0.001). Pain relief after 0.5% ropivacaine was 14% shorter than
      0.75% or 1% ropivacaine (P < 0.05). During the first 24 h after surgery, 30-37%
      of patients receiving ropivacaine required no analgesics compared with 10% of
      those receiving mepivacaine (P < 0.001). CONCLUSIONS: This study suggests that
      0.75% ropivacaine is the most suitable choice of local anesthetic for combined
      sciatic-femoral nerve block, providing an onset similar to mepivacaine and
      prolonged postoperative analgesia.

PMID- 10201677
TI  - Awareness during anesthesia: a closed claims analysis.
AB  - BACKGROUND: Awareness during general anesthesia is a frightening experience,
      which may result in serious emotional injury and post-traumatic stress disorder.
      We performed an in-depth analysis of cases from the database of the American
      Society of Anesthesiologists Closed Claims Project to explore the contribution of
      intraoperative awareness to professional liability in anesthesia. METHODS: The
      database of the Closed Claims Project is composed of closed US malpractice claims
      that have been collected in a standardized manner. All claims for intraoperative
      awareness were reviewed by the reviewers to identify patterns of causation and
      standard of care. Logistic regression analysis was used to identify independent
      patient and anesthetic factors associated with claims for recall during general
      anesthesia compared to other general anesthesia malpractice claims. RESULTS:
      Awareness claims accounted for 79 (1.9%) of 4,183 claims in the database,
      including 18 claims for awake paralysis, i.e., the inadvertent paralysis of an
      awake patient, and 61 claims for recall during general anesthesia, ie., recall of
      events while receiving general anesthesia. The majority of awareness claims
      involved women (77%), younger than 60 yr of age (89%), American Society of
      Anesthesiologists physical class I-II (68%), who underwent elective surgery
      (87%). Most (94%) claims for awake paralysis represented substandard care
      involving errors in labeling and administration, whereas care was substandard in
      only 43% of the claims for recall during general anesthesia (P < 0.001). Claims
      for recall during general anesthesia were more likely to involve women (odds
      ratio [OR] = 3.08, 95% confidence interval [CI] = 1.58, 6.06) and anesthetic
      techniques using intraoperative opioids (OR = 2.12, 95% CI = 1.20, 3.74),
      intraoperative muscle relaxants (OR = 2.28, 95% CI = 1.22, 4.25), and no volatile
      anesthetic (OR = 3.20, 95% CI = 1.88, 5.46). CONCLUSIONS: Deficiencies in
      labeling and vigilance were common causes for awake paralysis. Claims for recall
      during general anesthesia were more likely in women and with nitrous-narcotic
      relaxant techniques.

PMID- 10201678
TI  - Nerve injury associated with anesthesia: a closed claims analysis.
AB  - BACKGROUND: Nerve injury associated with anesthesia is a significant source of
      morbidity for patients and liability for anesthesiologists. To identify recurrent
      and emerging patterns of injury we analyzed the current American Society of
      Anesthesiologists (ASA) Closed Claims Project Database and performed an in-depth
      analysis of claims for nerve injury that were entered into the database since the
      authors' initial report of the subject. METHODS: The ASA Closed Claims Database
      is a standardized collection of case summaries derived from the closed claims
      files of professional liability insurance companies. Claims for nerve injury that
      were not included in the authors' 1990 report were reviewed in-depth. RESULTS:
      Six hundred seventy (16% of 4,183) claims were for anesthesia-related nerve
      injury. The most frequent sites of injury were the ulnar nerve (28%), brachial
      plexus (20%), lumbosacral nerve root (16%), and spinal cord (13%). Ulnar nerve
      (85%) injuries were more likely to have occurred in association with general
      anesthesia, whereas spinal cord (58%) and lumbosacral nerve root (92%) injuries
      were more likely to occur with regional techniques. Ulnar nerve injury occurred
      predominately in men (75%) and was also more apt to have a delayed onset of
      symptoms (62%) than other nerve injuries. Spinal cord injuries were the leading
      cause of claims for nerve injury that occurred in the 1990s. CONCLUSION: New
      strategies for prevention of nerve damage cannot be recommended at this time
      because the mechanism for most injuries, particularly those of the ulnar nerve,
      is not apparent.

PMID- 10201679
TI  - Fentanyl and morphine, but not remifentanil, inhibit acetylcholine release in
      pontine regions modulating arousal.
AB  - BACKGROUND: Opioids inhibit the rapid eye movement (REM) phase of sleep and
      decrease acetylcholine (ACh) release in medial pontine reticular formation (mPRF)
      regions contributing to REM sleep generation. It is not known whether opioids
      decrease ACh release by acting on cholinergic cell bodies or on cholinergic axon
      terminals. This study used in vivo microdialysis to test the hypothesis that
      opioids decrease ACh levels at cholinergic neurons in the laterodorsal tegmental
      nuclei (LDT) and LDT axon terminals in the mPRF. METHODS: Nine male cats were
      anesthetized with halothane, and ACh levels within the mPRF or LDT were assayed
      using microdialysis and high-pressure liquid chromatography (HPLC). ACh levels
      were analyzed in response to dialysis of the mPRF and LDT with Ringer's solution
      (control), followed by dialysis with Ringer's solution containing morphine
      sulfate (MSO4) or naloxone. ACh in the mPRF also was measured during either
      dialysis delivery or intravenous infusion of remifentanil and during dialysis
      delivery of fentanyl. RESULTS: Compared with dialysis of Ringer's solution,
      microdialysis with MSO4 decreased ACh by 23% in the mPRF and by 30% in the LDT.
      This significant decrease in ACh was antagonized by naloxone. MSO4 and fentanyl
      each caused a dose-dependent decrease in mPRF ACh when delivered by dialysis.
      Remifentanil delivered by continuous intravenous infusion or by dialysis into the
      mPRF did not alter mPRF ACh. CONCLUSIONS: Morphine inhibits ACh at the
      cholinergic cell body region (LDT) and the terminal field in the mPRF. ACh in the
      mPRF was not altered by remifentanil and was significantly decreased by fentanyl.
      Thus, MSO4 and fentanyl disrupt cholinergic neurotransmission in the LDT-mPRF
      network known to modulate REM sleep and cortical electroencephalographic
      activation. These data are consistent with the possibility that inhibition of
      pontine cholinergic neurotransmission contributes to arousal state disruption by
      opioids.

PMID- 10201680
TI  - Cardiopulmonary resuscitation: effect of CPAP on gas exchange during chest
      compressions.
AB  - BACKGROUND: Conventional cardiopulmonary resuscitation (CPR) includes 80-100/min
      precordial compressions with intermittent positive pressure ventilation (IPPV)
      after every fifth compression. To prevent gastric insufflation, chest
      compressions are held during IPPV if the patient is not intubated. Elimination of
      IPPV would simplify CPR and might offer physiologic advantages, but compression
      induced ventilation without IPPV has been shown to result in hypercapnia. The
      authors hypothesized that application of continuous positive airway pressure
      (CPAP) might increase CO2 elimination during chest compressions. METHODS: After
      appropriate instrumentation and measurement of baseline data, ventricular
      fibrillation was induced in 18 pigs. Conventional CPR was performed as a control
      (CPR(C)) for 5 min. Pauses were then discontinued, and animals were assigned
      randomly to receive alternate trials of uninterrupted chest compressions at a
      rate of 80/min without IPPV, either at atmospheric airway pressure (CPR(ATM)) or
      with CPAP (CPR(CPAP)). CPAP was adjusted to produce a minute ventilation of 75%
      of the animal's baseline ventilation. Data were summarized as mean +/- SD and
      compared with Student t test for paired observations. RESULTS: During CPR without
      IPPV, CPAP decreased PaCO2 (55+/-28 vs. 100+/-16 mmHg) and increased SaO2 (0.86+/
      0.19 vs. 0.50+/-0.18%; P < 0.001). CPAP also increased arteriovenous oxygen
      content difference (10.7+/-3.1 vs. 5.5+/-2.3 ml/dl blood) and CO2 elimination
      (120+/-20 vs. 12+/-20 ml/min; P < 0.01). Differences between CPR(CPAP) and
      CPR(ATM) in aortic blood pressure, cardiac output, and stroke volume were not
      significant. CONCLUSIONS: Mechanical ventilation may not be necessary during CPR
      as long as CPAP is applied. Discontinuation of IPPV will simplify CPR and may
      offer physiologic advantage.

PMID- 10201681
TI  - Contribution of peripheral chemoreception to the depression of the hypoxic
      ventilatory response during halothane anesthesia in cats.
AB  - BACKGROUND: The effects of inhalational anesthetics on the hypoxic ventilatory
      response are complex. This study was designed to determine the contribution of
      peripheral chemoreception to the depression of hypoxic ventilatory response seen
      with halothane anesthesia. METHODS: Cats were anesthetized with pentobarbital
      sodium and alpha-chloralose and artificially ventilated. Respiratory output was
      evaluated by phasic inspiratory activity of the phrenic nerve. In 12 cats, this
      activity was measured during inhalation of an hypoxic gas mixture with halothane,
      0, 0.1, and 0.8%, with intact or denervated carotid bodies. In 10 cats, a carotid
      body was isolated from the systemic circulation and perfused with hypoxic Krebs
      Ringer solution equilibrated with halothane, 0, 0.1, and 0.8%. RESULTS: The
      hypoxic ventilatory response was depressed in a dose-dependent manner during
      halothane anesthesia. In carotid body perfusion studies, the response was
      significantly depressed only with halothane, 0.80%. CONCLUSION: The hypoxic
      ventilatory response is depressed by a high dose of halothane through a
      peripheral effect at the carotid body.

PMID- 10201682
TI  - Local anesthetic inhibition of baseline potassium channels with two pore domains
      in tandem.
AB  - BACKGROUND: Recently, a new structural family of potassium channels characterized
      by two pore domains in tandem within their primary amino acid sequence was
      identified. These tandem pore domain potassium channels are not gated by voltage
      and appear to be involved in the control of baseline membrane conductances. The
      goal of this study was to identify mechanisms of local anesthetic action on these
      channels. METHODS: Oocytes of Xenopus laevis were injected with cRNA from five
      cloned tandem pore domain baseline potassium channels (TASK, TREK-1, TOK1, ORK1,
      and TWIK-1), and the effects of several local anesthetics on the heterologously
      expressed channels were assayed using two-electrode voltage-clamp and current
      clamp techniques. RESULTS: Bupivacaine (1 mM) inhibited all studied tandem pore
      potassium channels, with TASK inhibited most potently. The potency of inhibition
      was directly correlated with the octanol: buffer distribution coefficient of the
      local anesthetic, with the exception of tetracaine, to which TASK is relatively
      insensitive. The approximate 50% inhibitory concentrations of TASK were 709
      microM mepivacaine, 222 microM lidocaine, 51 microM R(+)-ropivacaine, 53 microM
      S(-)-ropivacaine, 668 microM tetracaine, 41 microM bupivacaine, and 39 microM
      etidocaine. Local anesthetics (1 mM) significantly depolarized the resting
      membrane potential of TASK cRNA-injected oocytes compared with saline-injected
      control oocytes (tetracaine 22+/-6 mV rs. 7+/-1 mV, respectively, and bupivacaine
      31+/-7 mV vs. 6+/-4 mV). CONCLUSIONS: Local anesthetics inhibit tandem pore
      domain baseline potassium channels, and they could depolarize the resting
      membrane potential of cells expressing these channels. Whether inhibition of
      these channels contributes to conduction blockade or to the adverse effects of
      local anesthetics remains to be determined.

PMID- 10201683
TI  - Mild therapeutic hypothermia for postischemic vasoconstriction in the perfused
      rat liver.
AB  - BACKGROUND: Mild hypothermia, a promising therapy being evaluated for various
      clinical situations, may suppress the formation of reactive oxygen species during
      reperfusion and may ameliorate microcirculatory perfusion failure (the "no-reflow
      phenomenon"). METHODS: Isolated rat livers underwent 30 min of perfusion, 2.5 h
      of ischemia, and 3 h of reperfusion. The temperature was maintained at 34 degrees
      C (mild hypothermia, n = 5) or 38 degrees C (normothermia, n = 6) for all three
      periods by perfusion of a modified Krebs Henseleit solution, air surface cooling,
      or both. A third group of livers was normothermic before and during ischemia and
      mildly hypothermic during reperfusion (reperfusion hypothermia, n = 6). Control
      livers had 3 h of perfusion at normothermia. Chemiluminescence (a measure of the
      generation of reactive oxygen species) and hepatic vascular resistance were
      monitored simultaneously to evaluate the effect of temperature on the formation
      of reactive oxygen species and the development of no reflow. Also measured were
      thiobarbituric acid reactive species and lactate dehydrogenase, as indicators of
      oxidative stress and cell injury. RESULTS: Mild hypothermia decreased formation
      of reactive oxygen species and postischemic increases in vascular resistance.
      Reperfusion hypothermia also decreased postischemic increases in vascular
      resistance, but not as effectively as did mild hypothermia. Levels of
      thiobarbituric acid reactive species were lower for reperfusion hypothermia than
      for mild hypothermia at only 0 and 30 min of reperfusion. Lactate dehydrogenase
      was significant only at 0 min of reperfusion for the normothermic group. Oxygen
      consumption did not change. CONCLUSION: The prevention of hepatic vascular injury
      by suppression of oxidative stress may be an important protective mechanism of
      mild hypothermia.

PMID- 10201684
TI  - Acute lung injury after instillation of human breast milk into rabbits' lungs:
      effects of pH and gastric juice.
AB  - BACKGROUND: The authors compared the lung injury in rabbits that occurred after
      tracheal instillation of human breast milk (HBM) acidified to pH 1.8 with
      hydrochloric acid (HCl), HBM at its native pH (7.0), and HBM acidified with
      gastric juice to pH 1.8 and 3.0. METHODS: The alveolar-to-arterial oxygen tension
      gradient and dynamic compliance were recorded before and hourly for 4 h after
      intratracheal instillation of 0.8 ml/kg HBM acidified with HCI (pH 1.8), HBM at
      its native pH (7.0), HBM acidified with gastric juice (pH 1.8 or 3.0), or 5%
      dextrose solution acidified with gastric juice (pH 1.8) as a control in 30 adult
      rabbits. The circulating neutrophil count and phagocyte oxidant activity were
      determined before and 1 and 4 h after instillation. RESULTS: The alveolar-to
      arterial oxygen tension gradient increased and dynamic compliance decreased
      significantly in all groups after instillation of HBM compared with baseline
      values and those in the control group. The severity of the lung injury after
      instillation of HBM at all pH values (1.8, 3.0, and 7.0) and after acidification
      with gastric juice or HCl was similar. The circulating neutrophil count increased
      steadily for 4 h after instillation (P < 0.013), whereas spontaneous phagocyte
      oxidant burst activity peaked at 1 h (P < 0.007) and returned to baseline by 4 h
      after instillation. CONCLUSIONS: The severity of the lung injury after tracheal
      instillation of 0.8 ml/kg HBM in rabbits is similar at pH values between 1.8 and
      7.0 after acidification with HCl or gastric juice. Tracheal instillation of HBM
      increases the circulating neutrophil count and phagocyte oxidant burst activity.

PMID- 10201685
TI  - Speed of onset and offset and mechanisms of ventilatory depression from
      sevoflurane: an experimental study in the cat.
AB  - BACKGROUND: Inhalational anesthetics depress breathing dose dependently. The
      authors studied the dynamics of ventilation on changes in end-tidal sevoflurane
      partial pressure. To learn more about the mechanisms of sevoflurane-induced
      respiratory depression, the authors also studied its influence on the dynamic
      ventilatory response to carbon dioxide. METHODS: Experiments were performed in
      cats anesthetized with alpha chloralose-urethane. For protocol 1, step changes in
      end-tidal sevoflurane partial pressure were applied and inspired ventilation was
      measured. Breath-to-breath inspired ventilation was related to the sevoflurane
      concentration in a hypothetical effect compartment based on an inhibitory sigmoid
      Emax model. For protocol 2, step changes in the end-tidal partial pressure of
      carbon dioxide were applied at 0, 0.5, and 1% end-tidal sevoflurane. The inspired
      ventilation-end-tidal partial pressure of carbon dioxide data were analyzed using
      a two-compartment model of the respiratory controller, which consisted of a fast
      peripheral and slow central compartment. Values are the mean +/- SD. RESULTS: In
      protocol 1, the effect-site half-life of respiratory changes caused by
      alterations in end-tidal sevoflurane partial pressure was 3.6+/-1.0 min. In
      protocol 2, at 0.50% sevoflurane, the central and peripheral carbon dioxide
      sensitivities decreased to 43+/-20% and 36+/-18% of control. At 1% sevoflurane,
      the peripheral carbon dioxide sensitivity decreased further, to 12+/-13% of
      control, whereas the central carbon dioxide sensitivity showed no further
      decrease. CONCLUSIONS: Steady state inspired ventilation is reached after 18 min
      (i.e., 5 half-lives) on stepwise changes in end-tidal sevoflurane. Anesthetic
      concentrations of sevoflurane have, in addition to an effect on pathways common
      to the peripheral and central chemoreflex loops, a selective effect on the
      peripheral chemoreflex loop. Sevoflurane has similar effects on ventilatory
      control in humans and cats.

PMID- 10201686
TI  - Effect of systemic morphine on the responses of convergent neurons to noxious
      heat stimuli applied over graded surface areas.
AB  - BACKGROUND: Stimulus intensity is a major determinant of the antinociceptive
      activity of opiates. This study focused on the influence of the spatial
      characteristics of nociceptive stimuli, on opiate-induced depressions of
      nociceptive transmission at the level of the spinal cord. METHODS: Anesthetized
      rats were prepared to allow extracellular recordings to be made from convergent
      neurons in the lumbar dorsal horn. The effects of systemic morphine (1 and 10
      mg/kg) were compared with those of saline for thermal stimuli of constant
      intensity, applied to the area of skin surrounding the excitatory receptive field
      (1.9 cm2) or to a much larger adjacent area (18 cm2). RESULTS: The responses
      (mean +/- SD) elicited by the 1.9-cm2 stimulus were not modified by 1 mg/kg
      intravenous morphine, although they were decreased by the 10-mg/kg dose (to 11+/
      4% of control values compared with saline; P < 0.05). In contrast, when the 18
      cm2 stimulus was applied, 1 mg/kg intravenous morphine produced a paradoxical
      facilitation of the neuronal responses (159+/-36% of control values; P < 0.05)
      and 10 mg/kg intravenous morphine resulted in a weaker depression of the
      responses (to 42+/-24% of control values; P < 0.05) than was observed with the
      smaller stimulus. CONCLUSIONS: Doses of systemic morphine in the analgesic range
      for rats had dual effects on nociceptive transmission at the level of the spinal
      cord, depending on the surface area that was stimulated. Such effects are
      difficult to explain in terms of accepted pharmacodynamic concepts and may
      reflect an opioid-induced depression of descending inhibitory influences
      triggered by spatial summation.

PMID- 10201687
TI  - Volatile anesthetics increase intracellular calcium in cerebrocortical and
      hippocampal neurons.
AB  - BACKGROUND: An increase in intracellular calcium concentration ([Ca2+]i) in
      neurons has been proposed as an important effect of volatile anesthetics, because
      they alter signaling pathways that influence neurotransmission. However, the
      existing data for anesthetic-induced increases in [Ca2+]i conflict. METHODS:
      Changes in [Ca2+]i were measured using fura-2 fluorescence spectroscopy in rat
      cortical brain slices at 90, 185, 370, and 705 microM isoflurane. To define the
      causes of an increase in [Ca2+]i, slices were studied in Ca2+-free medium, in the
      presence of Ca2+-channel blockers, and in the presence of the Ca2+-release
      inhibitor azumolene. The authors compared the effect of the volatile anesthetic
      with that of the nonanesthetic compound 1,2-dichlorohexafluorocyclobutane. Single
      dose experiments in CA1 neurons in hippocampal slices with halothane (360 microM)
      and in acutely dissociated CA1 neurons with halothane (360 microM) and isoflurane
      (445 microM) also were performed. RESULTS: Isoflurane at 0.5, 1, and 2 minimum
      alveolar concentrations increased basal [Ca2+]i in cortical slices in a dose
      dependent manner (P < 0.05). This increase was not altered by Ca2+-channel
      blockers or Ca2+-free medium but was reduced 85% by azumolene. The nonanesthetic
      1,2-dichlorohexafluorocyclobutane did not increase [Ca2+]i. In dissociated CA1
      neurons, isoflurane reversibly increased basal [Ca2+]i by 15 nM (P < 0.05).
      Halothane increased [Ca2+]i in dissociated CA1 neurons and CA1 neurons in
      hippocampal slices by approximately 30 nM (P < 0.05). CONCLUSIONS: (1) Isoflurane
      and halothane reversibly increase [Ca2+]i in isolated neurons and in neurons
      within brain slices. (2) The increase in [Ca2+]i is caused primarily by release
      from intracellular stores. (3) Increases in [Ca2+]i occur with anesthetics but
      not with the nonanesthetic 1,2-dichlorohexafluorocyclobutane.

PMID- 10201688
TI  - Recirculatory and compartmental pharmacokinetic modeling of alfentanil in pigs:
      the influence of cardiac output.
AB  - BACKGROUND: Cardiac output (CO) is likely to influence the pharmacokinetics of
      anesthetic drugs and should be accounted for in pharmacokinetic models. The
      influence of CO on the pharmacokinetic parameters of alfentanil in pigs was
      evaluated using compartmental and recirculatory models. METHODS: Twenty-four
      premedicated pigs were evaluated during halothane (0.6-2%) anesthesia. They were
      assigned randomly to one of three groups. One group served as control. In the
      other groups, the baseline CO was decreased or increased by 40% by pharmacologic
      intervention (propranolol or dobutamine). Boluses of alfentanil (2 mg) and
      indocyanine green (25 mg) were injected into the right atrium. Blood samples were
      taken for 150 min from the right atrium and aortic root. Arterial concentration
      time curves of indocyanine green and alfentanil were analyzed using compartmental
      models (two-stage and mixed-effects approach) and a recirculatory model, which
      can describe lung uptake and early distribution. RESULTS: The CO of individual
      pigs varied from 1.33 to 6.44 l/min. Three-compartmental modeling showed that CO
      is a determinant of the central compartment volume (V1, r2 = 0.54), fast
      peripheral compartment volume (V2, r2 = 0.29), steady state distribution volume
      (Vss, r2 = 0.29), fast distribution clearance (Cl12, r2 = 0.39), and elimination
      clearance (Cl10, r2 = 0.51). Recirculatory modeling showed that CO is a
      determinant of total distribution volume (r2 = 0.48), elimination clearance (r2 =
      0.54), and some distribution clearances. The pulmonary distribution volume was
      independent of CO. CONCLUSIONS: Cardiac output markedly influences the
      pharmacokinetics of alfentanil in pigs. Therefore, accounting for CO enhances the
      predictive value of pharmacokinetic models of alfentanil.

PMID- 10201689
TI  - Acetazolamide and amiloride inhibit pentobarbital-induced facilitation of
      nocifensive reflexes.
AB  - BACKGROUND: Neuronal excitation may result from stimulation of gamma-aminobutyric
      acid A (GABA(A)) receptors that prolong the channel opening, depolarizing the
      postsynaptic membrane. Drugs such as acetazolamide or amiloride can block GABA
      depolarization. Barbiturates facilitate nociceptive reflexes and also prolong the
      GABA(A) channel open-time. To evaluate the possible mechanism, the authors
      studied the impact of acetazolamide and amiloride on pentobarbital-induced
      nocifensive reflex facilitation. Because nitric oxide (NO) is a mediator of
      reflex facilitation, the authors evaluated the effects of NO synthase inhibition.
      METHODS: Nocifensive reflex thresholds were quantified with the hind paw
      withdrawal latency from radiant heat (HPW latency) in the rat. Nocifensive
      reflexes were facilitated with intraperitoneal injection of pentobarbital (30
      mg/kg). The authors tested the roles of GABA-mediated depolarization and NO in
      reflex facilitation by pretreatment with acetazolamide and amiloride and
      inhibition of NO synthase with L-NAME and 7-NI, respectively. Sedative effects of
      pentobarbital were evaluated with the righting reflex, the response to vibrissal
      stimulation, and plasma drug concentrations. RESULTS: Pentobarbital decreased the
      hind paw withdrawal latency from 11.2+/-1 to 8.3+/-1 s (P < 0.001). Pretreatment
      with each of the four test drugs limited the reduction in reflex facilitation
      after pentobarbital to 1.3 s or less, similar to the reduction seen after saline
      injection, without altering sedation. L-NAME increased plasma pentobarbital
      concentrations by 10% without changing the concentration associated with return
      of responsiveness. CONCLUSIONS: Pentobarbital-induced nocifensive reflex
      facilitation was inhibited by all four tested drugs without evidence of increased
      sedation. The results are consistent with a role for GABA(A) receptor-mediated
      depolarization in barbiturate-induced hyper-reflexia.

PMID- 10201690
TI  - Differential effects of lidocaine and mexiletine on relaxations to ATP-sensitive
      K+ channel openers in rat aortas.
AB  - BACKGROUND: In cardiac myocytes, lidocaine reduces but mexiletine increases
      adenosine triphosphate (ATP)-sensitive K+ currents, suggesting that these class
      Ib antiarrhythmic drugs may differentially modify the activity of ATP-sensitive
      K+ channels. The effects of lidocaine and mexiletine on arterial relaxations
      induced by K+ channel openers have not been studied. Therefore, the current study
      was designed to evaluate whether lidocaine and mexiletine may produce changes in
      relaxations to the ATP-sensitive K+ channel openers cromakalim and pinacidil in
      isolated rat thoracic aortas. METHODS: Rings of rat thoracic aortas without
      endothelia were suspended for isometric force recording. Concentration-response
      curves were obtained in a cumulative fashion. During submaximal contractions to
      phenylephrine (3 x 10(-7) M), relaxations to cromakalim (10(-7) to 3 x 10(-5) M),
      pinacidil (10(-7) to 3 x 10(-5) M), or diltiazem (10(-7) to 3 x 10(-4) M) were
      obtained. Lidocaine (10(-5) to 3 x 10(-4) M), mexiletine (10(-5) to 10(-4) M) or
      glibenclamide (5 x 10(-6) M) was applied 15 min before addition of phenylephrine.
      RESULTS: During contractions to phenylephrine, cromakalim and pinacidil induced
      concentration-dependent relaxations. A selective ATP-sensitive K+ channel
      antagonist, glibenclamide (5 x 10(-6) M), abolished these relaxations, whereas it
      did not alter relaxations to a voltage-dependent Ca2+ channel inhibitor,
      diltiazem (10(-7) to 3 x 10(-4) M). Lidocaine (more than 10(-5) M) significantly
      reduced relaxations to cromakalim or pinacidil in a concentration-dependent
      fashion, whereas lidocaine (3 x 10(-4) M) did not affect relaxations to
      diltiazem. In contrast, mexiletine (more than 10(-5) M) significantly augmented
      relaxations to cromakalim or pinacidil. Glibenclamide (5 x 10(-6) M) abolished
      relaxations to cromakalim or pinacidil in arteries treated with mexiletine (10(
      4) M). CONCLUSIONS: These results suggest that lidocaine impairs but mexiletine
      augments vasodilation mediated by ATP-sensitive K+ channels in smooth muscle
      cells.

PMID- 10201691
TI  - Individualized feedback of volatile agent use reduces fresh gas flow rate, but
      fails to favorably affect agent choice.
AB  - BACKGROUND: Cost reduction has become an important fiscal aim of many hospitals
      and anesthetic departments, despite its inherent limitations. Volatile anesthetic
      agents are some of the few drugs that are amenable to such treatment because
      fresh gas flow rate (FGFR) can be independent of patient volatile anesthetic
      agent requirement. METHODS: FGFR and drug use were recorded at the temporal
      midpoint of 2,031 general anesthetics during a 2-month preintervention period.
      Staff and residents were provided with their preintervention individual mean
      FGFR, their peer group mean, and educational material regarding volatile agent
      costs and low-flow anesthesia. FGFR and drug use were remeasured over a 2-month
      period (postintervention) immediately after this information (N = 2,242) and
      again 5 months later (delayed follow-up), for a further 2-month period (N =
      2,056). RESULTS: For all cases, FGFR decreased from 2.4+/-1.1 to 1.8+/-1.0 l/min
      (26% reduction) after the intervention and increased to 1.9+/-1.1 l/min (5%
      increase of preintervention FGFR) at the time of delayed follow-up. Use of more
      expensive volatile agents (desflurane and sevoflurane) increased during the study
      period (P < 0.01). In a subgroup of 44 staff members with more than five cases in
      all study periods, 42 members decreased their mean FGFR after intervention. At
      delayed follow-up, 30 members had increased their FGFR above postintervention
      FGFR but below their initial FGFR. After accounting for other predictors of FGFR,
      the effectiveness of the intervention was significantly reduced at follow-up (28%
      reduction), but retained a significant effect compared to preintervention FGFR
      (19% reduction). CONCLUSIONS: Although individual feedback and education
      regarding volatile agent use was effective at reducing FGFR, effectiveness was
      reduced without continued feedback. Use of more expensive volatile agents was not
      reduced by education regarding drug cost, and actually increased.

PMID- 10201692
TI  - Surgical subspecialty block utilization and capacity planning: a minimal cost
      analysis model.
AB  - BACKGROUND: Operational inefficiencies in the use of operating rooms (ORs) are
      hidden by traditional measures of OR utilization. To better detect these
      inefficiencies, the authors defined two new terms, underutilization and
      overutilization, and illustrated how these measures might be used to evaluate the
      use of surgical subspecialty ORs. The authors also described capacity planning
      (optimizing surgical subspecialty block time allotments) using a minimal cost
      analysis (MCA) model. METHODS: The authors evaluated post hoc all surgeries
      performed over 6 yr at a large teaching hospital. To prepare utilization
      estimates, surgical records were categorized relative to budgeted OR block time
      for each subspecialty. Surgical cases beginning and ending during budgeted OR
      block time were categorized as budgeted utilization, budgeted time not used for
      surgery was underutilization, and cases beginning before/after budgeted block
      time were classified as overutilization. Cases that overlapped budgeted and
      nonbudgeted OR block time were parsed and the portions were assigned
      appropriately. Probability distributions were fitted to the historical patterns
      of surgical demand, and MCA block time budgets were estimated that minimized the
      costs of underutilization and overutilization for each subspecialty. To
      illustrate the potential savings if these MCA budgets were implemented, the
      authors compared actual operational costs to the estimated MCA budget costs and
      expressed the savings as a percentage of actual costs. RESULTS: The authors
      analyzed data from 58,251 surgical cases and 10 surgical subspecialty blocks.
      Classic utilization for each block-day by surgical subspecialty ranged from 44
      113%. Average daily block-specific underutilization ranged from 16 to 60%,
      whereas overutilization ranged from 4 to 49%. CONCLUSIONS: Underutilization and
      overutilization are important measures because they may be used to evaluate the
      quality of OR schedules and the efficiency of OR utilization. Overutilization and
      underutilization also allow capacity planning using an MCA model This study
      indicated that the potential savings, if the MCA budgets were to be implemented,
      would be significant.

PMID- 10201693
TI  - Potassium channels: basic aspects, functional roles, and medical significance.

PMID- 10201694
TI  - Epidural anesthesia for cesarean section in patients with hypertrophic
      cardiomyopathy: a report of three cases.

PMID- 10201695
TI  - Malignant hyperthermia during desflurane-succinylcholine anesthesia for
      orthopedic surgery.

PMID- 10201696
TI  - Negative-pressure pulmonary edema associated with saber-sheath trachea.

PMID- 10201697
TI  - Anaphylactic shock to neuromuscular blocking agent: a familial history.

PMID- 10201698
TI  - SvO2 monitoring during spinal anesthesia and cesarean section in a parturient
      with severe cyanotic congenital heart disease.

PMID- 10201699
TI  - Acute dystonia during sevoflurane induction.

PMID- 10201700
TI  - Epidural blockade for labor and cesarean section with associated L4-5
      lipomyelocele.

PMID- 10201701
TI  - Epidural labor analgesia in a parturient with von Willebrand's disease type IIA
      and severe preeclampsia.

PMID- 10201702
TI  - An unexpected Penlon Sigma Elite Vaporizer leak.

PMID- 10201703
TI  - Diabetes and not lack of treatment with atenolol predicts decreased survival
      after noncardiac surgery.

PMID- 10201704
TI  - Catheter tip position and baricity of the local anesthetic have an impact on
      maldistribution in microcatheter CSA.

PMID- 10201705
TI  - Intrathecal sufentanil produces sensory changes without hypotension in male
      volunteers.

PMID- 10201706
TI  - Valve system performance.

PMID- 10201707
TI  - Are guidelines needed for the performance of invasive interventional procedures
      for minimally invasive cardiac surgery?

PMID- 10201708
TI  - Coronary sinus catheterization for minimally invasive cardiac surgery.

PMID- 10201709
TI  - Reducing the risk of perforation of the right ventricle during Port-Access
      minimally invasive cardiac procedures.

PMID- 10201710
TI  - Conflict of interest and the COPA.

PMID- 10201711
TI  - The role of the anesthesiologist in the management of chronic nonmalignant pain:
      a Canadian perspective.

PMID- 10201712
TI  - Differential latex allergy prevalence in anesthesiology subspecialties.

PMID- 10201713
TI  - Vaccines and physician behavior.

PMID- 10201715
TI  - Cosleeping in context: sleep practices and problems in young children in Japan
      and the United States.
AB  - OBJECTIVE: To determine the relationship between cosleeping and sleep problems in
      cultures with very different sleep practices. DESIGN: Interview study. SETTING:
      Families in urban Japan and the United States identified through pediatric and
      other professional contacts. PARTICIPANTS: Parents of healthy 6- to 48-month-old
      children (56 Japanese parents and 61 white US parents). All children had been
      breast-fed and lived in 2-parent, middleclass households. INTERVENTION: None.
      MAIN OUTCOME MEASURE: Sleep practices and sleep problems. RESULTS: More Japanese
      than US children coslept 3 or more times per week (59% vs. 15%, P<.001). All
      cosleeping Japanese children regularly slept all night with their parents (vs.
      11% of US cosleepers, P<.001). Japanese and US children did not differ in part
      night cosleeping (7% vs. 13%, P = .37). Most Japanese children had adult company
      and body contact as they fell asleep, and fathers slept separately in 23% of
      families. A greater proportion of US children had regular bedtime struggles and
      night waking. Within the US sample, cosleeping was associated with more bedtime
      struggles (P<.001), night waking (P<.01), and overall stressful sleep problems
      (P<.01). In the Japanese sample, cosleeping was associated only with night waking
      (P<.05); however, the proportion of cosleeping Japanese children with frequent
      night waking was at the level reported for US children who slept alone (30% vs
      23%, P = .47). CONCLUSIONS: Cultural differences seem to influence the
      relationship between sleep practices and sleep problems. The experience of the
      Japanese families indicates that cosleeping per se is not associated with
      increased sleep problems in early childhood.

PMID- 10201714
TI  - Analgesia and sedation in preterm neonates who require ventilatory support:
      results from the NOPAIN trial. Neonatal Outcome and Prolonged Analgesia in
      Neonates.
AB  - BACKGROUND: Preterm neonates are exposed to multiple painful procedures after
      birth and exhibit acute physiological responses to pain. Occurrence of early
      intraventricular hemorrhage within 24 to 72 hours after birth suggests a role of
      pain and stress in the multifactorial causation of severe intraventricular
      hemorrhage and periventricular leukomalacia. We proposed that such neurologic
      outcomes in preterm neonates who require ventilatory support may be reduced by
      morphine analgesia or midazolam sedation compared with a placebo. OBJECTIVES: To
      define the incidence of clinical outcomes in the target study population, to
      estimate the effect size and adverse effects associated with analgesia and
      sedation, and to calculate the sample size for a definitive test of this
      hypothesis. METHODS: Sixty-seven preterm neonates were randomized in a pilot
      clinical trial from 9 centers. Neonates of 24 to 32 weeks gestation were eligible
      if they had been intubated and required ventilatory support for less than 8 hours
      and if they were enrolled within 72 hours after birth. Exclusion criteria
      included major congenital anomalies, severe intrapartum asphyxia, and
      participation in other research studies. Severity of illness was assessed by the
      Clinical Risk Index for Babies, and neonates were randomized to receive
      continuous infusions of morphine sulfate, midazolam hydrochloride, or 10%
      dextrose (placebo). Masked study medications were continued as long as clinically
      necessary, then weaned and stopped according to predefined criteria. Levels of
      sedation (COMFORT scores) and responses to pain (Premature Infant Pain Profile
      scores) were measured before, during, and 12 hours after discontinuation of drug
      infusion. Cranial ultrasound examinations were performed as part of routine
      practice, and poor neurologic outcomes were defined as neonatal death, severe
      intraventricular hemorrhage (grade III or IV), or periventricular leukomalacia.
      RESULTS: No significant differences occurred in the demographic, clinical, and
      socioeconomic variables related to mothers and neonates in the 3 groups or in the
      severity of illness at birth as measured by Clinical Risk Index for Babies
      scores. Two neonates in the placebo group and 1 neonate in the midazolam group
      died; no deaths occurred in the morphine group. Poor neurologic outcomes occurred
      in 24% of neonates in the placebo group, 32% in the midazolam group, and 4% in
      the morphine group (likelihood ratio chi2 = 7.04, P = .03). Secondary clinical
      outcomes and neurobehavioral outcomes at 36 weeks' postconceptional age were
      similar in the 3 groups. Responses elicited by endotracheal tube suction
      (Premature Infant Pain Profile scores) were significantly reduced during the
      morphine (P<.001) and midazolam (P = .002) infusions compared with the placebo
      group. CONCLUSIONS: This pilot trial suggests that preemptive analgesia given by
      continuous low-dose morphine infusion may reduce the incidence of poor neurologic
      outcomes in preterm neonates who require ventilatory support. Limitations in the
      sample size of this pilot study suggest that these results should be confirmed in
      a large multicenter randomized trial.

PMID- 10201716
TI  - The epidemiology of adolescent homicide in North Carolina from 1990 to 1995.
AB  - BACKGROUND: Rates of homicides by adolescents under age 18 years tripled from
      1984 to 1994. Most studies report data on urban adolescents and young adults as a
      single age group (age 15-24 years), but homicide characteristics among
      adolescents, especially those younger than 15 years, may differ from those of
      young adults. OBJECTIVE: To describe the homicide characteristics among
      adolescents age 11 to 18 years in North Carolina from 1990 to 1995. METHODS: A
      retrospective, descriptive analysis of adolescent homicides using the medical
      examiner database. Police interviews provided additional information for cases
      from 1993 to 1995. RESULTS: There were 419 victims from 1990 to 1995 (average
      annual rate: 9.7 per 100000 adolescents; 9.9 in urban counties, 7.1 in rural).
      Victims were mostly ages 15 to 18 years (85%), male (79%), and black (76%); 48%
      lagged behind in school, and, by police report, 40% had a criminal record. Only
      23% of the identified perpetrators were strangers. Firearms (59% were handguns)
      were used in 83% of homicides. Proportionally more younger adolescents (age 11-14
      years) were killed by means other than firearms than 15- to 18-year-olds (chi2 =
      24.2, P = .007). Drug-related motives (23%) were most common, followed by non
      drug-related altercations (20%) and retaliations (17%). CONCLUSIONS:
      Proportionally more North Carolina adolescents than urban young adults (ages 15
      24 years) were killed by firearms (83% vs. 75%). Proportionally fewer adolescents
      were killed by police, strangers, or intimate partners. Interventions should
      include reducing access to firearms and drugs, and helping adolescents develop
      nonviolent strategies to resolve disputes. Efforts should be focused on
      adolescents who lag behind in school and have criminal records.

PMID- 10201717
TI  - Varicella immunization practices and the factors that influence them.
AB  - OBJECTIVES: To evaluate the varicella immunization practices of physicians in
      Rochester, NY, and to identify factors that predict whether physicians administer
      varicella vaccine to children. DESIGN: Evaluation of a 40-item survey addressing
      varicella immunization practices and opinions about varicella immunization that
      was sent to 241 pediatricians and family physicians. RESULTS: A total of 172
      physicians (71.4%) completed the survey. Sixty-three percent administer the
      vaccine to some or all varicella-susceptible children aged 1 through 5 years,
      while 57% administer it to children aged 6 through 11 years, and 74% administer
      it to adolescents 12 years and older. Physicians who did not offer the
      immunization were more likely to believe that (1) the vaccine should not be given
      to preadolescent children because "varicella is a normal part of childhood"; (2)
      by giving the vaccine, varicella may shift from being primarily a childhood
      illness to being primarily an adult illness; (3) children get enough
      immunizations already and should not be given additional immunizations to prevent
      varicella; (4) it may be preferable to only immunize immunocompromised
      individuals and their close contacts; and (5) it would cost too much to immunize
      all American children who have not had varicella. Physicians most likely to offer
      the vaccine were pediatricians and those whose patients were covered primarily by
      private insurance plans. After becoming aware of morbidity and mortality rates
      for varicella-related complications, many physicians who did not administer the
      vaccine, or administered it only at the request of a parent, indicated that they
      would be more likely to offer it. CONCLUSIONS: Most physicians in the Rochester
      area administer varicella vaccine, especially to adolescents 12 years and older.
      Specialty, predominant insurance type billed, and various opinions characterized
      those who did not offer the immunization. Providing these physicians with
      information about varicella-related complications may make them more likely to
      immunize.

PMID- 10201718
TI  - A comparison of New York City playground hazards in high- and low-income areas.
AB  - OBJECTIVE: To compare playground hazards in high- and low-income neighborhoods.
      DESIGN: Forty-five playgrounds were randomly selected from the 9 New York City
      community districts that met our study criteria and were divided into high-and
      low-income groups based on comparison to the median of the median incomes ($24452
      per year) of the 9 districts. Playgrounds are maintained by the City of New York
      Parks and Recreation Department and were assessed by one of us (S.A.S.) using a
      standardized on-site survey based on the US Consumer Product Safety Commission's
      guidelines for public playground safety. MAIN OUTCOME MEASURES: Total hazards per
      play area were subdivided into 3 categories: park design hazards, equipment
      maintenance hazards, and equipment hazards relating to fall injuries. A play area
      was defined as an individual set of equipment. RESULTS: Twenty-five (56%) of the
      parks were located in low-median-income districts and contained 98 (53%) of the
      total play areas. High- and low-income playgrounds did not differ significantly
      in the amount or type of equipment, mean fall injury hazards per play area, or
      mean park design hazards per play area. Low-income districts had a significantly
      higher mean total hazards per play area (6.1 vs. 4.2; P = .02) and mean equipment
      maintenance hazards per play area (2.1 vs. 1.0; P = .02). CONCLUSION:
      Significantly more hazards per play area were identified in the low-income group
      compared with the high-income group.

PMID- 10201719
TI  - Direct observation of health-habit counseling of adolescents.
AB  - OBJECTIVES: To determine the rate of health-habit counseling of adolescents
      seeing community family physicians and to identify the factors associated with
      the delivery of recommended preventive counseling services. DESIGN: Cross
      sectional multimethod study emphasizing direct observation of patient visits.
      SETTING: Community family practices in northeast Ohio. PATIENTS OR OTHER
      PARTICIPANTS: Adolescents (n = 445) aged 11 to 21 years who were being seen for
      outpatient visits to community family physicians (n = 119) during 2 days of
      observation by trained research nurses. MAIN OUTCOME MEASURE: Direct observation
      of the delivery of clinical preventive counseling services recommended by the
      Guidelines for Adolescent Preventive Services. RESULTS: During the 445 visits
      made by adolescents, the most frequently delivered counseling service was
      exercise advice (13%). At least 1 health-habit counseling service was delivered
      during 38% of visits. In multivariable analyses, older patient age was strongly
      associated with increased service delivery. Visits for well care, longer visits,
      and new patient visits were also associated with the provision of counseling.
      Visits including preventive counseling services were on average 2.5 minutes
      longer than visits without preventive counseling. CONCLUSIONS: The rates of
      delivery of preventive counseling services in clinical practice were low, raising
      concern about the feasibility of current recommendations. The practical
      implementation of prevention guidelines may require a greater use of well-care
      visits and longer patient visits than are currently used in community family
      practice.

PMID- 10201720
TI  - Frequency of digital rectal examination in children with chronic constipation.
AB  - OBJECTIVES: To determine the frequency of performance of digital rectal
      examination by primary care practitioners on children with chronic constipation
      and to assess its effect on therapy. PATIENTS AND METHODS: One hundred twenty
      eight children referred for chronic constipation to the Division of Pediatric
      Gastroenterology at Schneider Children's Hospital, New Hyde Park, NY, as well as
      their parents were questioned as to whether a digital rectal examination was ever
      performed prior to referral. All children underwent subsequent digital rectal
      examination by a pediatric gastroenterologist and recommended treatment regimens
      were compared with pretreatment regimens. The patients evaluated were a mix of
      private-insurance and Medicaid patients referred by pediatricians in the general
      community. RESULTS: Ninety-eight (77%) of the children referred for chronic
      constipation were found to have never had a digital rectal examination performed
      prior to referral. Fifty-three (54%) of these children were found to have fecal
      impaction. Only 19 (21%) were found to have minimal to no stool retention on
      digital examination. Enema therapy had been infrequently used to "clean out" the
      colon in referred children. Seventy percent were treated with multiple enema
      therapy following digital rectal examination. Organic causes of constipation were
      identified in 3 patients. CONCLUSIONS: Digital rectal examination is often not
      performed in the examination of the child with chronic constipation. The digital
      examination can help differentiate functional constipation from an organic
      process and may alter the course of therapy.

PMID- 10201721
TI  - Guideline for the management of pediatric idiopathic constipation and soiling.
      Multidisciplinary team from the University of Michigan Medical Center in Ann
      Arbor.
AB  - OBJECTIVE: To develop an evidence-based guideline for the primary pediatric care
      of children (birth to 18 years old) with idiopathic constipation and soiling.
      DATA SOURCES: References were identified through a MEDLINE search from January
      1975 through January 1998 to address 3 focus questions: (1) the best path to
      early, accurate diagnosis; (2) best methods for adequate clean-out; and (3) best
      approaches to promote patient and family compliance with management. DATA
      SELECTION: Twenty-five references were identified. DATA EXTRACTION: References
      were reviewed by a multidisciplinary team and graded according to the following
      criteria: randomized controlled trial; controlled trial, no randomization;
      observational study; and expert opinion. Evidence tables were developed for each
      focus question. DATA SYNTHESIS: An algorithm and clinical care guideline were
      developed by consultation and consensus among team members. Emphasis was placed
      on methods to promote early identification of pediatric idiopathic constipation
      and soiling, to recognize points of referral, and to increase patient and family
      compliance with treatment through use of education, developmentally based
      interventions, and variables for tracking success of management. CONCLUSION: An
      algorithm and guideline for pediatric idiopathic constipation and soiling are
      presented for use by primary care physicians.

PMID- 10201722
TI  - Medical assessment and legal outcome in child sexual abuse.
AB  - OBJECTIVE: To examine the relationship of behavioral symptoms, interview
      disclosures, and physical examination findings with changing legal outcomes in
      child sexual abuse. DESIGN: Retrospective case series. SETTING: Hospital- and
      community-based multidisciplinary child abuse evaluation teams in the same county
      in 2 periods. PATIENTS: Children ages 0 to 17 years referred for evaluation of
      sexual abuse. MAIN OUTCOME MEASURES: Substantiation by child protective services,
      issuance of a warrant by law enforcement authorities, and criminal penalties were
      compared with reported changes in behavior, disclosure by the child, and physical
      evidence on examination. RESULTS: Among 497 children evaluated in 1991-1992 and
      1995-1996, those with a positive examination finding were 2.5 times more likely
      to result in a criminal prosecution with a finding of perpetrator guilt (P<.001).
      Similar rates of disclosure, positive examination findings, child protective
      services substantiation, and warrant issuance were noted in the 2 periods.
      Decreasing rates of guilt determination and increasing criminal penalties were
      identified in 1995-1996 (P<.002). Disclosure of child sexual abuse during medical
      assessment was significantly associated with a positive physical examination
      finding, child protective services substantiation, and issuance of a warrant, but
      not a finding of guilt or criminal penalty. CONCLUSIONS: Medical assessment plays
      an important role in the overall community response to child sexual abuse. While
      behavioral symptoms and disclosure are important in medical treatment and child
      protective services investigation, positive physical findings are associated with
      a finding of guilt. There is a trend toward less finding of guilt and more years
      of criminal penalty that is not explained by case characteristics.

PMID- 10201723
TI  - Selection of neonates for neuroprotective therapies: one set of criteria applied
      to a population.
AB  - OBJECTIVES: To estimate the proportion of children with cerebral palsy (CP) who
      had signs of birth asphyxia" in the early hours of life, and to examine the
      nature of the illnesses in those infants. DESIGN: Population-based case-control
      study. SETTING: All births in 4 northern California counties, 1983 through 1985.
      SUBJECTS: Eighty-four full-term singleton children surviving to age 3 years with
      spastic CP and 366 full-term control children. MAIN OUTCOME MEASURE: Moderate or
      severe spastic CP. RESULTS: Of 84 full-term children with spastic CP, 18 had 5
      minute Apgar scores of less than 6, 20 required intubation for ventilation in the
      delivery room, and 5 had an initial blood pH of 7.00 or less. Three (3.6%) of the
      84 children had all 3 signs evaluated, a prevalence of 0.019 per 1000 survivors.
      All 3 had neonatal seizures. When we relaxed the pH cutoff to 7.10 or less, there
      were 19 children with CP who met at least 2 criteria. Eight of these 19 infants
      were born in level I facilities. In these children there was evidence of maternal
      or infant infection (n = 7), abnormal coagulation factor, thrombosis, or
      thrombocytopenia (n = 8); or other complication predating birth (n = 9).
      CONCLUSIONS: Neuroprotective therapy offered to neonates with these early
      characteristics, even if perfectly effective, would be unlikely to prevent most
      CP. Most of these depressed infants with CP had nonasphyxial conditions that may
      have contributed to adverse neurological outcome.

PMID- 10201724
TI  - Bruises in infants and toddlers: those who don't cruise rarely bruise. Puget
      Sound Pediatric Research Network.
AB  - OBJECTIVES: To determine the frequency and location of bruises in normal infants
      and toddlers, and to determine the relationship of age and developmental stage to
      bruising. DESIGN: Cross-sectional survey. SETTING: Community primary care
      pediatric offices. SUBJECTS: Children younger than 36 months attending well-child
      care visits. METHODS: Prospective data collection of demographics, developmental
      stage, and presence and location of bruises. Any medical condition that causes
      bruises as well as known or suspected abuse was also recorded. A chi2 test or
      Fisher exact test was used to determine the significance of differences. MAIN
      OUTCOME MEASURES: Presence and location of bruises as related to age and
      developmental stage. RESULTS: Bruises were found in 203 (20.9%) of 973 children
      who had no known medical cause for bruising and in whom abuse was not suspected.
      Only 2 (0.6%) of 366 children who were younger than 6 months and 8 (1.7%) of 473
      children younger than 9 months had any bruises. Bruises were noted in only 11
      (2.2%) of 511 children who were not yet walking with support (cruising). However,
      17.8% of cruisers and 51.9% of walkers had bruises (P<.001). Mean bruise
      frequency ranged from 1.3 bruises per injured child among precruisers (range, 1-2
      bruises) to 2.4 per injured child among walkers (range, 1-11). The most frequent
      site of bruises was over the anterior tibia and knee. Bruises on the forehead and
      upper leg were common among walkers, but bruises on the face and trunk were rare,
      and bruises on the hands and buttocks were not observed at any age. There were no
      differences in bruise frequency by sex. African American children were observed
      to have bruises much less frequently than white children (P<.007). CONCLUSIONS:
      Bruises are rare in normal infants and precruisers and become common among
      cruisers and walkers. Bruises in infants younger than 9 months and who are not
      yet beginning to ambulate should lead to consideration of abuse or illness as
      causative. Bruises in toddlers that are located in atypical areas, such as the
      trunk, hands, or buttocks, should prompt similar concerns.

PMID- 10201725
TI  - Development and validation of the injury severity assessment survey/parent
      report: a new injury severity assessment survey.
AB  - OBJECTIVE: To develop and pilot test a telephone-based survey instrument that
      enables parents to identify and characterize the body region and severity of
      childhood injuries using the Abbreviated Injury Scale (AIS) scoring system.
      DESIGN: A prospective cross-sectional survey. SETTING: The emergency department
      of an urban, tertiary care, pediatric trauma center. PARTICIPANTS: One hundred
      forty-seven parents of children younger than 18 years and seen in the emergency
      department for acute treatment of an unintentional injury. INTERVENTIONS: None.
      MAIN OUTCOME MEASURE: The degree of agreement, measured as sensitivity,
      specificity, and kappa statistic, between medical record information and parents'
      responses to the telephone survey regarding the identification and
      characterization of clinically significant (AIS > or =2) injuries. RESULTS: The
      survey, known as the Injury Severity Assessment Survey/Parent Report, was
      developed via a systematic review of the AIS 1990 manual. Answers to questions
      were developed in a way that enabled automated coding of responses into AIS
      scores or ranges of scores. The sensitivity of the survey (its ability to detect
      injuries scoring 2 or more on the AIS that were documented in the medical record)
      varied somewhat by the body region of injury, ranging from 88% for head, face,
      neck, and spine injuries to 95% for extremity injuries. Intermediate sensitivity
      (92%) was noted for the detection of significant chest and abdomen injuries. The
      specificity of the survey (its ability to rule out the presence of a significant
      injury when one was not documented in the medical record) was more than 95% in
      each of the 3 body region groups. The kappa statistics for the 3 body region
      groups ranged from 0.89 to 0.92. CONCLUSIONS: A new telephone-based survey has
      been developed that enables parents to characterize their child's injuries by
      body region and to differentiate between minor injuries and more significant
      injuries using a well-established injury classification system. This survey has a
      significant advantage over previous telephone-based or written surveys of
      childhood injuries and may be particularly valuable in population-based (e.g.,
      random-digit dial surveys) or multi-institutional studies of pediatric injuries.

PMID- 10201727
TI  - Teaching physicians how to break bad news: a 1-day workshop using standardized
      parents.
AB  - OBJECTIVE: To evaluate the effectiveness of a training program using standardized
      parents (SPs) to improve the performance of pediatric intensive care fellows in
      communicating bad news to parents. DESIGN: Self-controlled crossover design.
      SETTING: Tertiary pediatric intensive care unit in a university-affiliated
      children's hospital. PARTICIPANTS: Seven pediatric intensive care fellows and 4
      trained volunteers (2 sets of SPs) participated in the study. METHODS: Two case
      scenarios of children admitted to the intensive care unit with a near-fatal
      diagnosis were used for the fellow's interactions with the SPs. The SPs had
      received 15 hours of training in role playing, performance evaluation, and giving
      feedback to the physicians. At the end of the first session, SPs provided
      feedback to the physicians under each of the 5 following categories:
      communication skills, content issues, support systems, interventions, and parent
      perceptions. During the second session, the parent meeting was repeated with a
      new but similar case scenario and a different set of SPs. Both sessions were
      videotaped, and a rater blinded to the order of the sessions used a weighted
      scale based on a checklist to score changes in physician performance. RESULTS:
      The performance by the fellows showed a significant mean (+/-SEM) improvement in
      scores of 18.1 (+/-5.2) points (P = .007) between the first and the second
      sessions. Ranking of session scores revealed that physician performance improved
      significantly during the second session (Wilcoxon signed rank test, P = .002).
      CONCLUSIONS: To our knowledge this is the first study that demonstrates short
      term improvement in physician performance in conveying bad news in a pediatric
      intensive care setting using SPs in a 1-day workshop.

PMID- 10201728
TI  - Radiological case of the month. Transient acute renal failure of the newborn.

PMID- 10201726
TI  - Reducing obesity via a school-based interdisciplinary intervention among youth:
      Planet Health.
AB  - OBJECTIVE: To evaluate the impact of a school-based health behavior intervention
      known as Planet Health on obesity among boys and girls in grades 6 to 8. DESIGN:
      Randomized, controlled field trial with 5 intervention and 5 control schools.
      Outcomes were assessed using preintervention (fall 1995) and follow-up measures
      (spring 1997), including prevalence, incidence, and remission of obesity.
      PARTICIPANTS: A group of 1295 ethnically diverse grade 6 and 7 students from
      public schools in 4 Massachusetts communities. INTERVENTION: Students
      participated in a school-based interdisciplinary intervention over 2 school
      years. Planet Health sessions were included within existing curricula using
      classroom teachers in 4 major subjects and physical education. Sessions focused
      on decreasing television viewing, decreasing consumption of high-fat foods,
      increasing fruit and vegetable intake, and increasing moderate and vigorous
      physical activity. MAIN OUTCOME MEASURES: Obesity was defined as a composite
      indicator based on both a body mass index and a triceps skinfold value greater
      than or equal to age- and sex-specific 85th percentiles. Because schools were
      randomized, rather than students, the generalized estimating equation method was
      used to adjust for individual-level covariates under cluster randomization.
      RESULTS: The prevalence of obesity among girls in intervention schools was
      reduced compared with controls, controlling for baseline obesity (odds ratio,
      0.47; 95% confidence interval, 0.24-0.93; P = .03), with no differences found
      among boys. There was greater remission of obesity among intervention girls vs.
      control girls (odds ratio, 2.16; 95% confidence interval, 1.07-4.35; P = .04).
      The intervention reduced television hours among both girls and boys, and
      increased fruit and vegetable consumption and resulted in a smaller increment in
      total energy intake among girls. Reductions in television viewing predicted
      obesity change and mediated the intervention effect. Among girls, each hour of
      reduction in television viewing predicted reduced obesity prevalence (odds ratio,
      0.85; 95% confidence interval, 0.75-0.97; P = .02). CONCLUSION: Planet Health
      decreased obesity among female students, indicating a promising school-based
      approach to reducing obesity among youth.

PMID- 10201729
TI  - Picture of the month. Jervell and Lange-Nielsen syndrome (long QT syndrome).

PMID- 10201730
TI  - Pathological case of the month. Osteoma cutis/pseudohypoparathyroidism.

PMID- 10201731
TI  - Parental leave and pediatric residents.

PMID- 10201732
TI  - E-mail and medical education.

PMID- 10201733
TI  - Updated bronchodilator analysis.

PMID- 10201734
TI  - Auricular rehabilitation with bone-anchored titanium implants.
AB  - OBJECTIVE: To evaluate the effectiveness of the bone-anchored titanium implants
      in auricular reconstructions. STUDY DESIGN: Six patients who received implants
      for an auricular reconstruction were followed prospectively. Four patients had
      lost their ears to cancer, and the other two had congenital aural atresia.
      METHODS: All patients were thoroughly evaluated by the reconstruction team, which
      included a surgeon, a prosthodontist, and a facial prosthetist. Three patients
      were evaluated audiologically for a bone-anchored hearing aid. Four patients
      received implants in a single-stage procedure, and two underwent a two-stage
      procedure. A gold bar with retaining clips was used to anchor the prosthetic ear
      in four patients, and magnets were used in the remaining two. RESULTS: All six
      patients are completely satisfied with their reconstructions. No failures,
      extrusions, or bony complications were encountered. One patient had recurrent
      dermatitis, which subsided when his gold bar was replaced with magnets.
      CONCLUSION: Implanted under the guidance of an appropriate prosthetic team, bone
      anchored titanium implants provide patients with a safe, reliable, adhesive-free
      method to anchor auricular prostheses with recovery of their normal appearance.

PMID- 10201735
TI  - An integrated theory of the no-reflow phenomenon and the beneficial effect of
      vascular washout on no-reflow.
AB  - OBJECTIVES: No-reflow is failure of perfusion in free tissue transfer despite
      adequate arterial inflow. The objectives of this study were to construct a theory
      of interactive mechanisms of the no-reflow phenomenon and to determine whether
      preischemic vascular washout could increase flap ischemia tolerance. STUDY
      DESIGN: The evidence for the role of various mechanisms in the development of no
      reflow is reviewed, and an integrated network proposed. A rat-groin free flap
      model is used to test preischemic vascular washout with normal saline,
      heparinized normal saline, lactated Ringer's solution, Tis-U-Sol, and Viaspan.
      METHODS: The mean ischemia tolerance of this flap without any therapeutic
      intervention was first determined, using 22 animals. An additional 50 animals
      were used to compare with the control group the ischemia tolerance of flaps
      washed out with the above fluids before their ischemic period. RESULTS: The
      critical ischemia time 50 (time after which half of the flaps are expected to
      survive and half, die) of the untreated flap is 23.4 hours in this model (P<.05).
      Flaps washed out with normal saline or lactated Ringer's solution have
      significantly worse ischemia tolerance (P<.0001). Flaps washed out with Tis-U-Sol
      or Viaspan behave similarly to the control group (P>.57). Flaps receiving
      preischemic washout with heparinized normal saline (4,000 units/L) had a
      significantly better outcome than the control group (P<.027). CONCLUSIONS:
      Preischemic washout with normal saline, lactated Ringer's solution, or
      heparinized Tis-U-Sol is detrimental for flap survival after ischemia, Tis-U-Sol-
      and Viaspan-treated flaps do have ischemia tolerance similar to the control
      group, and flaps washed out with heparinized normal saline have a survival
      advantage in this model.

PMID- 10201736
TI  - A meta-analysis of swimming and water precautions.
AB  - OBJECTIVE: To reconcile conflicting reports concerning the incidence of otorrhea
      in children with tympanostomy tubes who swim without ear protection. STUDY
      SELECTION: Articles were identified by MEDLINE search, Current Contents, and
      references from review articles, textbook chapters, and retrieved reports.
      Controlled trials of water precautions following tympanostomy tube placement were
      selected by independent observers and scored on 10 measures of study validity.
      Five English-language articles met all inclusion criteria. DATA EXTRACTION: Data
      were abstracted for an endpoint of otorrhea following swimming without ear
      protection with a minimum follow-up of 6 weeks. DATA SYNTHESIS: Pooled analysis
      of 619 children revealed a rate difference of -5.04 (95% confidence interval
      [CI], -11.62 to 1.54). No significant difference in the incidence of otorrhea was
      noted between patients who swam without ear protection and nonswimmers.
      CONCLUSION: There is no increase in incidence of otorrhea in children who swim
      without ear protection compared with children who do not swim following
      tympanostomy tube placement.

PMID- 10201737
TI  - Frontal sinus obliteration using a laterally based pedicled pericranial flap.
AB  - OBJECTIVE: Fractures of the frontal sinus represent one of the more uncommon
      injuries of the maxillofacial skeleton. In an effort to avoid potential mucocele
      formation, frontal sinus obliteration has been put forward as the treatment of
      choice when there has been significant disruption of normal frontal sinus
      drainage. Traditionally, sinus obliteration has been accomplished with
      nonvascularized free adipose tissue or bone grafts and a variety of alloplastic
      materials. We developed a laterally based pedicled pericranial flap to accomplish
      frontal sinus obliteration. STUDY DESIGN/METHODS: A total of 10 consecutive
      patients underwent obliteration of the frontal sinus with a vascularized,
      pedicled, laterally based pericranial flap. The patients were clinically followed
      prospectively to ascertain whether any adverse effects could be detected.
      RESULTS: With a follow-up ranging from 6 months to 2 years, we have observed no
      adverse effects in any of the patients in whom this procedure was performed.
      CONCLUSIONS: Based on our preliminary results, we believe that the laterally
      based pedicled pericranial flap appears to provide readily available vascularized
      tissue, with no distant donor morbidity. It represents an inexpensive, safe, and
      effective modality that should be considered when treating this type of injury.

PMID- 10201738
TI  - Surgical experience and complications during endonasal sinus surgery.
AB  - OBJECTIVE/HYPOTHESIS: The introduction of optical aids for endonasal sinus
      surgery has not produced the expected drop in the rate of serious intraoperative
      complications. STUDY DESIGN/METHODS: 1. Retrospectively, consecutive procedures
      of different surgeons were analyzed in regard to major complications (periorbital
      injury, orbital lesion, dural injury, endocranial lesion, damage to the internal
      carotid artery). The chronological distribution was transformed into a personal
      learning curve. 2. From our own experience and as surveyors, we analyzed the
      experiences of surgeons having encountered severe complications and compared them
      with the above-mentioned learning curve. RESULT: In total, 1,500 operations
      carried out by five surgeons with 16 serious complications were assessed. For the
      learning curve, the following stages were defined. stage I: greatest risk of
      complication, with dural injury (1st to 30th operation); stage II, slighter risk
      of complication, with frequent periorbital injuries (31st to 180th operation);
      and stage III, least risk, corresponding to an experienced surgeon. Serious
      complications occur most frequently among experienced surgeons. CONCLUSION: The
      beginner enjoys the most effective type of assistance, in the form of personal
      guidance of an experienced surgeon who is constantly present during the first 30
      operations, and who should then be readily available during the next 70 operative
      procedures. The use of multimedia software appears to be helpful, though its
      actual value still remains to be determined. The experienced surgeon in
      particular must be willing to exercise repeated self-criticism to keep his or her
      rate of complications to a minimum.

PMID- 10201739
TI  - Th-2 type cytokine receptors in allergic rhinitis and in response to topical
      steroids.
AB  - OBJECTIVES: Th-2 type cytokine production (Interleukin-4 [IL-4] and interleukin-5
      [IL5]) has been demonstrated to play a significant role in the pathophysiology of
      allergic rhinitis (AR), and the treatment of AR with topical corticosteroids has
      been shown to reduce the expression of Th-2 type cytokines in vivo. However, the
      contribution and expression of Th-2 type cytokine receptors in AR and their
      response to corticosteroid treatment remain to be clarified. Objectives of the
      current study are 1. To examine the expression of the cytokine IL-4 and IL-5
      receptors (IL-4R and IL-5R) in a nasal allergen challenge model and to contrast
      this with the expression of the receptor for the Th-1 type cytokine, interferon
      gamma receptor (IFN-gammaR), and 2. to examine the effects of pretreatment with
      topical corticosteroid before allergen challenge on the expression of these same
      receptors. STUDY DESIGN: Randomized prospective study involving 14 ragweed
      allergic subjects evenly divided between placebo and corticosteroid pretreatment.
      METHODS: Immunocytochemistry (alkaline phosphatase-antialkaline phosphatase
      labeling [APAAP] technique) was used to stain nasal biopsy specimens before and
      after allergen challenge. Antibodies used included anti-CD3, CD4, CD8, major
      basic protein (MBP), IL-4R, IL-5R, and IFN-gammaR. RESULTS: Following allergen
      challenge, we observed a significant increase in the Th-2 type cytokine receptors
      (IL-4R and IL-5R; P<.05), as well as a significant decrease in the expression of
      the Th-1 type cytokine receptor (IFN-gammaR; P<.05). Pretreatment with topical
      corticosteroids before nasal allergen challenge resulted in decreased expression
      of IL-4R (P<.05) and IL-5R (P<.05) and increased expression of IFN-gammaR
      (P<.05). Further, IL-4R and IL-5R expression correlated with eosinophil
      infiltration in the tissues. CONCLUSIONS: We have demonstrated that in AR,
      cytokine receptors for IL-4, IL-5, and IFN-gamma follow a similar pattern to
      their ligands. In addition, pretreatment with topical corticosteroids was shown
      to alter the cytokine receptor expression pattern from a Th-2 profile more toward
      a Th-1 profile.

PMID- 10201740
TI  - Interaction between fibronectin and eosinophils in the growth of nasal polyps.
AB  - OBJECTIVES: The aim of this study was to determine roles of fibronectin and
      eosinophils in the etiology of nasal polyposis. STUDY DESIGN: We designed a
      cohort study of cases with nasal polyposis. Sampled nasal polyps were
      differentiated by their histopathologic characteristics, and compared by size and
      computed tomography (CT) stage. METHODS: The size of nasal polyps was determined
      on the basis of the endoscopic findings, and the extent of sinusitis was
      evaluated by CT staging. Nasal polyp samples were taken from 82 patients during
      ethmoidectomy and differentiated by morphologic characteristics, infiltration
      cell types, or fibronectin positivity. Then their sizes and CT stages were
      compared. In addition, correlation among these histological characteristics was
      analyzed. RESULTS: Nasal polyps showing edematous morphology, eosinophil
      infiltration, or fibronectin expression were significantly large in size.
      Concerning CT stages, only the infiltration cell type showed a significant
      difference. Significant correlation among edematous morphology, eosinophil
      infiltration, and fibronectin expression was also recognized. CONCLUSIONS: These
      findings suggest that interaction between eosinophils and fibronectin may play a
      role in edema formation, which contributes to the growth of nasal polyps.

PMID- 10201741
TI  - Microvasculature, blood flow, and vasoreactivity in rabbit sinus mucosa after
      surgery.
AB  - OBJECTIVES: To study the circulatory integrity of the sinus mucosa following
      surgery, the vascular anatomy, blood flow, and vasoconstrictor response of the
      regenerated microcirculatory network were analyzed. STUDY DESIGN: Forty-six New
      Zealand White rabbits were operated on unilaterally with either a modified
      radical operation (MRO) or middle meatal antrostomy (MMA), using the nonoperated
      sinus for control purposes. After surgery, the animals were left to heal for 1
      month. METHODS: Vascular casts were prepared with a low-viscosity methyl
      methacrylate resin and studied by scanning electron microscopy. Blood flow was
      measured by means of radiolabeled microspheres (tin 113 [113Sn]). The
      vasoconstrictor response to oxymetazoline at increasing concentrations was
      measured with laser Doppler flowmetry. RESULTS: The number of vessels increased
      significantly in the regenerated mucosa. The vascular casts displayed a rich
      microcirculation with local signs of angiogenesis. However, there was no
      difference in blood flow between the operated cavities and their control sides.
      Following MRO the regenerated mucosa was more sensitive to the vasoconstrictor
      effect of oxymetazoline, compared with the control side. This difference was not
      evident in the MMA-operated sinuses. CONCLUSIONS: In this model, surgery does not
      seriously interfere with the sinus blood flow, although the regenerated mucosa
      did display an altered vasoreactivity. These findings should be considered in
      relation to the effects of surgery intended to limit local inflammation and to
      ensure the ventilation of the sinuses.

PMID- 10201742
TI  - Gustatory otalgia and wet ear syndrome: a possible cross-innervation after ear
      surgery.
AB  - HYPOTHESIS: The chorda tympani and Arnold's nerves have close approximation to
      each other and their cross-innervation is possible after ear surgery. STUDY
      DESIGN: A retrospective study was performed with a temporal bone pathology case
      and two clinical cases as representatives of such a possibility. Patients had
      severe otalgia and wet ear during gustatory stimulation. METHODS: A temporal bone
      pathology case was studied under a light microscope. Earache and/or wet ear were
      provoked during gustatory stimulation. Wet ear was tested with iodine-starch
      reaction after the subject tasted lemon juice. RESULTS: The temporal bone
      specimen has clusters of regenerated fibers in the tympanic cavity in the area of
      the chorda tympani and Arnold's nerves, suggesting a possibility of mixing. There
      are regenerated fibers in the iter chordae anterius, showing successful bridging
      of the chorda tympani nerves across a long gap. Detachment of the skin over the
      operated mastoid bowl obscured signs in one clinical case. Another clinical case
      of gustatory wet ear showed objective evidence of cross-innervation with iodine
      starch reaction. CONCLUSION: The detachment procedure and iodine-starch reaction
      were the proofs that the signs were related to regenerated fibers. This is the
      first report of gustatory otalgia and wet ear after ear surgery.

PMID- 10201743
TI  - Reconstruction of the ossicular chain in the middle ear with glass ionomer
      cement.
AB  - OBJECTIVES: The aim of this study is to describe a method to repair small defects
      (1 to 2 mm) of the ossicular chain by means of glass ionomer cement (GIC) alone.
      Larger defects can be repaired with a combination of GIC and a platinum wire
      prosthesis. GIC is a two-component hybrid material consisting of inorganic glass
      particles surrounded by an insoluble hydrogel matrix. GIC has been used by
      dentists for many years, but only a few reports describe the use of GIC in human
      middle ear surgery. Many investigators have proved that most GICs are
      biocompatible, biostable, and well tolerated by bone and soft tissue. STUDY
      DESIGN: From 1994 to 1996 GIC was used in 97 middle ear operations. In 44 cases
      small defects of the ossicular chain were reconstructed with GIC alone. The
      observation period ranged from 1 to 4 years. METHODS: Nearly all operations were
      performed with the patient under local analgesia. RESULTS: The postoperative air
      bone gap was less than 20 dB in 83.3%. Compared with results from comparable
      operations, the GIC results are significantly better. One patient had reoperation
      because the cement had loosened from the bone as a result of faulty GIC operation
      technique. CONCLUSIONS: Repair of defects of the ossicular chain with GIC is an
      easy, efficient, quick, and inexpensive method, which ought to be kept in mind
      for future middle ear surgery. No complications in the middle ear were related to
      GIC.

PMID- 10201744
TI  - Long-term results of surgery for temporal bone paragangliomas.
AB  - OBJECTIVES: Assessment of the long-term results of surgery for temporal bone
      paragangliomas with special consideration of the patient's ability to cope with
      the functional deficits. STUDY DESIGN: Retrospective review of 36 patients who
      had undergone resection of a temporal bone paraganglioma 10 to 15 years
      previously. Assessment of the patients' subjective view of the functional outcome
      and quality of life by a questionnaire. METHODS: Clinical records were reviewed
      regarding size of tumor, technique of surgery, supportive therapy, and tumor
      recurrence. Patients were sent a 50-item questionnaire evaluating their quality
      of life and the preoperative and postoperative function of cranial nerves VII
      through XII. RESULTS: A complete tumor removal was achieved in 30 patients (83%).
      There was only one tumor recurrence. The major negative effects of surgery
      involved hearing and dysphagia, which deterioriated in 14 and 12 patients,
      respectively. Thirty-five of the 36 patients (97%) reported that, despite
      deterioration, the cranial nerve deficits were still acceptable. Seventy-five
      percent of the patients regained their preoperative quality of life and 97%
      returned to their previous occupation in 1 to 2 years. CONCLUSIONS: The otologic
      extradural approach allowed complete tumor removal in 83%, with minimal
      perioperative morbidity. No surgically induced central nervous system lesions
      occured. Tracheostomy was avoided and all patients resumed oral feeding. Full
      rehabilitation after removal of class C and CD paragangliomas may take 1 to 2
      years. However, the fact that 97% of the patients finally resumed normal social
      life showed the ability of most patients to cope with the sequelae of surgery
      even in class C and CD paragangliomas.

PMID- 10201745
TI  - Efficacy of treatments for posterior canal benign paroxysmal positional vertigo.
AB  - OBJECTIVE: This study was performed to determine the relative effectiveness of
      several passive head maneuvers for treating benign paroxysmal positional vertigo.
      STUDY DESIGN: This prospective study used 87 subjects diagnosed by their
      physicians with unilateral benign paroxysmal positional vertigo of the posterior
      semicircular canal. METHODS: Subjects were randomly assigned to three treatment
      groups: modified Epley maneuver, modified Epley maneuver with augmented head
      rotations, and modified Semont maneuver. They were interviewed 1 week after
      receiving one maneuver. If subjects desired further treatment, they were treated
      again with the same maneuver, a methodology repeated until subjects desired no
      further treatment; they were telephoned 3 and 6 months after the last treatment.
      RESULTS: The groups did not differ significantly, but subjects decreased
      significantly on vertigo intensity and frequency and improved significantly on
      independence in activities of daily living. Before treatment, tasks requiring
      pitch rotations of the head induced vertigo; common comorbid conditions were
      osteoporosis, cervical spine problems, and head trauma. CONCLUSIONS: These data
      suggest that augmented head rotations are unnecessary and that the modified Epley
      and Semont maneuvers are equally effective in the remediation of vertigo in this
      population.

PMID- 10201746
TI  - Hearing preservation in microvascular decompression for trigeminal neuralgia.
AB  - OBJECTIVE/HYPOTHESIS: Sensorineural hearing loss is a disturbing complication of
      microvascular decompression (MVD) for trigeminal neuralgia with an incidence of
      1% to 23.8%. Cerebellar retraction with increasing I-V interpeak latency (IPL)
      during intraoperative brainstem auditory evoked potentials (BAEP) has been
      identified as the chief cause of acoustic injury. This study was designed to
      eliminate cerebellar retraction by a modification of the standard suboccipital
      craniectomy. STUDY DESIGN: Nine consecutive patients undergoing surgery for
      trigeminal neuralgia were prospectively selected for this study between 1994 and
      1995. METHODS: Preoperative and postoperative audiograms were obtained.
      Preoperative and intraoperative BAEPs were performed. The surgical modification
      describes initiating a partial mastoidectomy to enhance early recognition and
      delineation of the sigmoid and transverse sinuses crucial to maximizing the
      lateral extent of the craniectomy. The additional exposure gained by this
      technique allows for improved visualization of the brainstem without cerebellar
      retraction. RESULTS: All patients were relieved of neuralgic pain. Postoperative
      IPL values were not significantly different from preoperative values (4.9+/-0.6
      vs. 4.7+/-0.3 ms). Maintaining IPL of less than 1.5 ms is considered critical for
      preventing injury to the auditory nerve. In this study the average increase in
      postoperative IPL was 0.25 ms for the ipsilateral ear and 0.1 ms for the
      contralateral ear. CONCLUSIONS: The authors offer a surgical modification of the
      standard suboccipital craniectomy and furnish intraoperative neurophysiologic
      data to demonstrate how cerebellar compression can be eliminated and hearing
      preserved in MVD for trigeminal neuralgia.

PMID- 10201747
TI  - Age at implantation: its importance in pediatric cochlear implantation.
AB  - OBJECTIVE: To assess the influence of age at implantation on speech perception
      and speech intelligibility following pediatric cochlear implantation. STUDY
      DESIGN: A prospective study was undertaken on a consecutive group of 126
      congenital and prelingually deaf children up to 4 years after implantation. The
      study group was confined to prelingually deaf children less than 7 years of age
      at the time of implantation. All had implantation with the same multichannel
      cochlear implant system. No child was lost to follow-up, and there were no
      exclusions from the study. METHODS: The Iowa Matrix Closed Set Sentence test,
      connected discourse tracking, categories of auditory performance, and speech
      intelligibility rating were used to assess the speech perception (closed and open
      set) and speech intelligibility of the children with implants. Regression
      analysis and Spearman rank correlation coefficients were used to assess the
      correlation between the outcome measures with age at implantation. The setting
      was a tertiary referral pediatric cochlear implant center in the United Kingdom.
      RESULTS: Age at implantation positively correlated with preimplantation
      assessment performance and with most of the outcome measures up to 24 months
      following implantation. However, at the 3-and 4-year intervals following
      implantation, age at implantation was found to be a strong negative predictor of
      all the outcomes studied (correlation coefficients ranging from -0.44 to -0.58,
      all statistically significant [P<.05]). CONCLUSIONS: The results of the present
      study provide strong evidence that prelingually deaf children should receive
      implants as early as possible to facilitate the later development of speech
      perception skills and speech intelligibility and thus maximize the health gain
      from the intervention. However, because of the wide variation in individual
      outcomes, age alone should not be used as a criterion to decide implant
      candidacy.

PMID- 10201749
TI  - Localization of static positional nystagmus with the ocular fixation test.
AB  - OBJECTIVE: Characteristics of static positional nystagmus (SPN) (i.e.,
      persistency, direction fixed, direction changing) are observed in both peripheral
      and central disturbances and possess no localizing value for vestibular lesions.
      Our objective was to investigate whether the ocular fixation test as applied to
      SPN could assist in localizing vestibular lesions. STUDY DESIGN: A 3-year
      prospective study that included 43 patients with SPN. METHODS: All patients
      underwent a standard vestibular test battery and cerebral imaging (7, computed
      tomography scan; 36, magnetic resonance imaging). The ocular fixation index (OFI)
      was calculated by the ratio of the mean slow component velocity of SPN (measured
      with red light-emitting diode fixation) to that measured in darkness, multiplied
      by 100. An OFI less than 50 was considered normal. RESULTS: In 33 of 35 patients
      whose OFI was less than 50, the cerebral imaging was normal and a peripheral
      vestibular lesion was diagnosed (two benign tumors of the fourth ventricle were
      missed). In all eight patients whose OFI was greater than 50, the cerebral
      imaging was abnormal and a central vestibular lesion was noted. CONCLUSIONS:
      These results indicate that the visual suppression of SPN does, indeed, permit
      the localization of vestibular lesions. The predictive value of the ocular
      fixation test on the origin of SPN is greater than 94% for peripheral lesions and
      100% for central disorders.

PMID- 10201748
TI  - Cost-effectiveness of the diagnostic evaluation of vertigo.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of several diagnostic tests used in
      the evaluation of vertigo. STUDY DESIGN: Cost-effectiveness analysis, using data
      from retrospective case review. METHODS: Charts and test results were reviewed
      from 192 outpatients seen in an academic tertiary referral center for evaluation
      of vertigo. Cost-effectiveness analysis was performed using decision analysis
      software, data from office and hospital charges, and expert-based estimations of
      the utility of different test outcomes. Sensitivity analysis was performed using
      standard algorithms and wide variable ranges. RESULTS: We found that audiologic
      testing, posturography, and electronystagmography were the most cost-effective
      tests, and that magnetic resonance imaging and blood tests had the lowest cost
      effectiveness. The analysis was sensitive to the effects of financial costs of
      tests but, with a few exceptions, was typically not sensitive to the utility of
      test outcomes or the distribution of test results. CONCLUSIONS: The use of cost
      effectiveness analysis, the estimation of utility of test outcomes, and
      techniques of sensitivity analysis should help guide the clinician's decision
      making on appropriate testing for patients with vertigo.

PMID- 10201750
TI  - Expression of Fas/APO-1 and apoptosis of keratinocytes in human cholesteatoma.
AB  - OBJECTIVES: The Fas/APO-1 is a cell surface receptor protein known to trigger
      apoptosis when conjugated with Fas ligand or specific agonistic antibodies. The
      present study investigated the expression of Fas/APO-1 and apoptotic cell death
      in both normal and cholesteatoma epithelia. STUDY DESIGN: Ten cholesteatomas and
      retroauricular skins were taken during middle ear operations in the Ajou
      University Hospital for this study. METHODS: In situ terminal deoxynucleotidyl
      transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) staining and agarose
      gel electrophoresis of genomic DNA were used for detection of apoptosis. The
      expression patterns of Fas/APO-1 protein were confirmed by immunoblot and
      immunohistochemical analysis. RESULTS: In situ TUNEL staining revealed many
      positively stained nuclei in 9 of 10 suprabasal layers of cholesteatoma
      epithelium, whereas few positively stained cells were found on the granular layer
      of retroauricular skins. Typical "ladder pattern" was seen on the gel
      electrophoresis of the genomic DNA of cholesteatoma. Immunoblot analysis and
      immunohistochemical studies revealed that Fas/APO-1 protein was expressed in 8 of
      10 cholesteatoma epithelia, whereas retroauricular skin showed negative reaction.
      CONCLUSION: These results show the upregulated expression of Fas/APO-1 and
      increased apoptotic cell death in cholesteatoma epithelium. Because Fas/APO-1 is
      known as an apoptosis-triggering protein, it is suggested that the accumulation
      of keratin debris is due to increased apoptotic cell death related to Fas/APO-1
      protein.

PMID- 10201751
TI  - Amplification of RNA from archival human temporal bone sections.
AB  - BACKGROUND: The amplification of DNA from celloidin-embedded human temporal bone
      sections by polymerase chain reaction (PCR) has been applied to some auditory
      diseases, such as herpes zoster oticus and hearing loss caused by the mutations
      of mitochondrial DNA. However, few studies have reported detection of RNA from
      temporal bone sections. OBJECTIVES: Because RNA analysis from temporal bone
      sections may elucidate the development of the diseases in the auditory,
      vestibular, and facial nerves, the authors investigated whether RNA in these
      sections can be amplified by reverse transcription (RT)-PCR. METHODS: Sections
      that were formalin-fixed, decalcified, and embedded between 1972 and 1986 were
      used. Nucleic acid was extracted from the celloidin-embedded temporal bone
      sections and subjected to RT-PCR. Human alpha-tubulin RNA was reverse transcribed
      to cDNA and amplified by nested PCR using two sets of primers that were designed
      to distinguish cDNA from genomic DNA based on the presence of an intron between
      the primers. RESULTS: Human alpha-tubulin RNA was detected in 11 of 14 temporal
      bone sections (79%) by RT-PCR. RNA was detected in even the oldest sections,
      which were processed in 1972. CONCLUSIONS: These results indicate that RNA can be
      analyzed from archival celloidin-embedded human temporal bone sections.

PMID- 10201752
TI  - Recognition of a dominant epitope in bovine heat-shock protein 70 in inner ear
      disease.
AB  - OBJECTIVE: To investigate the specificity of antibodies to heat-shock protein 70
      (HSP70) in patients with idiopathic, progressive, bilateral sensorineural hearing
      loss (IPBSNHL) and Meniere disease. STUDY DESIGN: Test immunoreactivity of
      patients' sera using recombinant human (rh) and bovine (rb) HSP70, as well as
      segments representing different regions of bovine HSP70 as antigen. METHODS: Sera
      were tested by Western blotting. RESULTS: Of 52 patients with IPB-SNHL, 40 sera
      reacted only with rbHSP70; 12 reacted with both rbHSP70 and rhHSP70. Sera from 13
      patients with IPBSNHL and from 8 with Meniere disease were tested on the panel of
      bovine HSP70 segments. Eleven and 7 samples, respectively, reacted with amino
      acid segment 427-461 from the carboxy (C)-terminal region of the molecule.
      CONCLUSION: In IPBSNHL and Meniere disease, antibodies are directed primarily
      against an epitope(s) within the C-terminal region of HSP70 where diversity in
      sequence among different species, including possible pathogens, is greatest.
      These findings may provide clues to the pathogenesis or specific serodiagnosis
      (or both) of diseases of the inner ear.

PMID- 10201754
TI  - Improved nerve regeneration with neutralization of transforming growth factor
      beta1.
AB  - OBJECTIVES: Recovery of injured peripheral nerves depends on a balance between
      Schwann cell regeneration and scar formation. Transforming growth factor-beta1
      (TGF-beta1) has been implicated as a humoral stimulus in scar formation. The
      neutralization of TGF-beta1 has been beneficial in the reduction of fibrosis.
      This study was to identify the presence of TGF-beta1 in regenerating peripheral
      nerve and to measure motor nerve regeneration by the neutralization of TGF-beta1
      in neural wounds. STUDY DESIGN: A randomized study of rat sciatic nerve
      regeneration. METHOD: Sciatic nerve axotomy was performed, followed by serial
      immunohistochemical staining by anti-TGF-beta1 at 12 to 216 hours (n = 5). Two
      groups (n = 10) with sciatic axotomy and epineural repair were treated with a 7
      day perineural administration of neutralizing antibody of TGF-beta1 or saline
      carrier via subcutaneous silicone infusion port. A control group (n = 10) without
      axotomy with anti-TGF-beta1 administration was established. At 12 weeks the
      compound muscle action potential amplitude (CMAP) and the muscle twitch strength
      generated by the gastrocnemiussoleus muscle complex were measured. RESULTS: TGF
      beta1 was qualitatively present with maximal concentration by 72 to 144 hours.
      CMAP amplitude in the anti-TGF-beta1/axotomy group was 49.6% of the control and
      the axotomy/saline group was 31% of the control. Muscle twitch strength was 74%
      and 46.5%, respectively. These differences were statistically significant, P =
      .05. CONCLUSIONS: The presence of TGF-beta1 at regenerating nerve sites was
      confirmed. The benefit of neutralization of transforming growth factor on CMAP
      and muscle twitch strength was shown. These results suggest improved regeneration
      at nerve injury sites with neutralization of TGF-beta1.

PMID- 10201753
TI  - Effects of immunosuppression on the development of cochlear disease in the MRL
      Fas(lpr) mouse.
AB  - OBJECTIVES: The MRL-Fas(lpr) mouse, an animal that spontaneously develops
      multisystemic autoimmune disease, has been proposed as model of immune-mediated
      inner ear disease. Previous studies revealed that this mouse manifested elevated
      auditory brainstem response thresholds, hydropic degeneration of strial cells,
      and antibody deposition within strial capillaries. As the etiology of the
      observed strial disease may be immune, genetic, or uremic, a study was designed
      to attempt to delineate between these possible etiologic factors. STUDY DESIGN:
      Prospective, controlled animal study. METHODS: Dexamethasone, which is known to
      suppress autoantibody production and glomerulonephritis in these animals, was
      administered systemically on a daily basis to experimental animals, beginning at
      6 weeks of age. Control animals received no treatment. Animals were allowed to
      age, with control animals predictably manifesting systemic disease at 20 weeks of
      age, at which point all animals were sacrificed. RESULTS: Animals receiving
      dexamethasone treatment manifested a significant reduction in serum
      immunoglobulin levels, lymphoid hyperplasia, and a significant improvement in the
      level of renal function. However, morphologic analysis revealed a persistence of
      strial disease despite the elimination of strial antibody deposition. CONCLUSION:
      The results of this experiment support the hypothesis that genetic mechanisms may
      be responsible for the observed strial disease. Further studies are under way to
      confirm these findings.

PMID- 10201755
TI  - Evaluation of endoscope sheaths as viral barriers.
AB  - OBJECTIVES: Evaluate ENT endoscope sheaths as barriers to virus passage. STUDY
      DESIGN: "Defective" sheaths covering an endoscope were challenged with virus to
      determine how many virus particles could be recovered from the endoscope.
      METHODS: Sheaths with small laser-drilled holes (2 to 30 microm) were challenged
      with high-titer virus suspensions (10(8) viruses/mL). The inside of the sheath
      and the endoscope were separately rinsed to recover any virus that penetrated
      through the hole in the sheath. In an attempt to assess the possible importance
      of holes in the sheaths, a sequential test was conducted with an initial virus
      challenge outside a defective sheath (30-micron hole in the sheath), after which
      the possibly contaminated endoscope was removed and inserted into a second
      defective sheath (with a 20-micron hole at the same location) to determine
      whether the contaminating virus would pass outward through the second sheath.
      RESULTS: Small volumes of virus-containing fluid penetrated through the hole,
      e.g., 500 virus particles passed through one of three 30-microm holes. A
      significant fraction of those virus particles was occasionally found on the
      endoscope after removal from the sheath. Similar results were obtained with
      sheaths that had small tears (34-84 microm in length, from punctures with fine
      wires). Although some virus penetration could occur during the initial challenge
      contaminating the endoscope, no virus was detected passing outward through the
      second sheath. CONCLUSIONS: Use of a sheath combined with intermediate level
      disinfection should provide a safe instrument for ENT endoscopy.

PMID- 10201756
TI  - Peer review: studying the major otolaryngology journals.
AB  - OBJECTIVE: To determine if the otolaryngology literature is comparable to other
      surgical specialty journals with respect to quality and types of articles
      published. METHODS: The four major otolaryngology journals--Annals of Otology,
      Rhinology and Laryngology, Archives of Otolaryngology--Head and Neck Surgery,
      Laryngoscope, and Otolaryngology--Head and Neck Surgery--were studied for 6
      months and examined for the following variables: 1) proportion of clinical or
      basic science research, 2) proportion of prospective or retrospective studies, 3)
      types of statistics used, 4) sample sizes of the studies, and 5) proportion of
      single case reports. A composite group of surgical specialty journals consisting
      of Journal of Bone and Joint Surgery, Neurosurgery, and Ophthalmology was also
      studied for the same time period. The otolaryngology journals and other specialty
      journals were compared with respect to each of these variables, after which the
      comparison was conducted within the group of otolaryngology journals. RESULTS:
      Analysis of 905 articles, comprising 508 articles from the four major
      otolaryngology journals and 397 articles from the composite of the other
      specialty journals, was conducted. No significant difference in the proportion of
      single case reports between the otolaryngology journals (15.0%) and the other
      specialty journals (12.8%) was noted (P = .364). The otolaryngology journals had
      a significantly higher proportion of basic research than the other specialty
      journals (27.4% vs. 14.5%, P<.001) as well as a higher percentage of prospective
      studies (62.1% vs. 49.0%, P = .001). The studies in the otolaryngology journals
      had a much lower mean sample size than those in the other specialty journals
      (70.2 vs. 373.8, P = .010). No difference between the two groups was found in the
      use of statistics (P = .228). Among the otolaryngology journals, Laryngoscope was
      found to publish fewer single case reports than the other three journals, and
      Annals of Otology, Rhinology and Laryngology had the highest proportion of
      prospective studies (P = .031 and .012, respectively). No differences were found
      for sample sizes and use of statistical analysis (P = .266 and P = .710,
      respectively) among the otolaryngology journals. CONCLUSIONS: The otolaryngology
      literature compares quite favorably with the literature of other surgical
      specialties, excelling in prospective studies and basic science research. It only
      lags with respect to sample size. The study composition among the different major
      otolaryngology journals is largely similar with respect to basic study
      parameters, suggesting comparable quality among the journals.

PMID- 10201757
TI  - Lateral dural sinus thrombosis in childhood.
AB  - OBJECTIVES: To present etiology, diagnosis, and treatment of dural sinus
      thrombosis (DST) in children. To discuss the diagnostic role of contrast-enhanced
      computed tomography (CECT) and to evaluate the controversial treatment modalities
      of anticoagulation, surgical drainage of the infected sinus, and ligation of the
      internal jugular vein (IJV). STUDY DESIGN: Retrospective chart review and
      analysis of computed tomography (CT) scans and follow-up visits to document the
      clinical outcome. METHODS: Between 1986 and 1996, CT scans of 15 children
      revealed DST. These patients were further investigated. RESULTS: The etiology
      could be divided in three groups: group A, infection (6); group B, trauma (6);
      and group C, coagulation disorders. There were neither symptoms nor clinical
      findings specifically related to DST but rather, these were related to the
      underlying disease or condition (otitis media, skull base fractures). Diagnosis
      was made by CECT in all cases. Fusobacterium necrophorum was found in 4 of 6
      patients in group A. Early mastoidectomy with incision and drainage of the
      thrombosed sigmoid sinus was performed in patients in group A. Postoperative
      intravenous (IV) heparin was given; however, no ligation of the IJV became
      necessary. In all patients in group C, protein C or protein S deficiency, or
      both, was detected. CONCLUSIONS: CECT with adequate window-level settings allows
      the diagnosis of a DST with high sensitivity. Treatment of choice for septic DST
      consists of administration of antibiotics and early surgical drainage. We
      recommend anticoagulation therapy in children with septic DST during their
      hospitalization.

PMID- 10201758
TI  - A prospective randomized double-blind trial of fibrin glue for pain and bleeding
      after tonsillectomy.
AB  - OBJECTIVES: The notable morbidity of tonsillectomy includes considerable
      postoperative pain and a rate of postoperative bleeding that have remained
      largely uninfluenced by modern surgical techniques or medication. Fibrin glue is
      known to have a hemostatic effect in some settings, and there is research
      suggesting it may also reduce postoperative pain. The objectives of this study
      were to evaluate the effect of fibrin glue on pain and bleeding after
      tonsillectomy. STUDY DESIGN: A prospective randomized double-blind study was
      performed on 50 consecutive adult patients undergoing tonsillectomy for chronic
      tonsillitis. METHODS: After removal of both tonsils the tonsillar fossa randomly
      assigned to the treatment protocol was coated with fibrin glue. The other side
      was left unaltered. The patient was then monitored for postoperative bleeding and
      wound healing, and a patient-based pain assessment instrument was used to
      evaluate symptoms every 8 hours for 10 days after surgery. RESULTS: Detailed
      evaluation of the pain scores allowed the authors to create a pain profile for
      what the typical patient experiences over the first 10 postoperative days, as
      well as during the course of a single day. The pain remains relatively constant
      for the first 7 days and begins to decrease only on the eighth postoperative day.
      During a single day there is increased pain in the morning compared with noon and
      evening. However, no statistically significant difference was detected in
      postoperative pain, bleeding, or healing between the wounds treated with fibrin
      glue and controls. CONCLUSIONS: The patient-based pain evaluation data should aid
      the physician in preoperative outcome counselling and targeted prescription of
      pain medication. However, contrary to previous indications, the authors cannot
      substantiate a significant beneficial effect of fibrin glue in postoperative pain
      control. Furthermore, we did not find its action as a hemostatic agent clinically
      applicable in this setting, and thus find no indication for the routine use of
      fibrin glue in tonsillectomy.

PMID- 10201759
TI  - Objective aerodynamic and acoustic measurement of voice improvement after
      phonosurgery.
AB  - HYPOTHESIS: Objective analysis of the outcome of phonosurgery is needed to allow
      comparison of different surgical techniques or indications, or both. We tried to
      demonstrate that measurement of mean oral airflow during the production of a
      sustained vowel could be used in combination with acoustic measurements such as
      jitter or shimmer for assessment of voice improvement after phonosurgery. STUDY
      DESIGN: This prospective study included 27 consecutive patients who underwent
      phonosurgery during a 3-month period. METHOD: Perceptual analysis served as the
      "gold standard." Objective measurements (oral airflow, jitter, shimmer) on the
      most stable portion of a sustained vowel /a/ were made using the EVA system (SQ
      Lab, Aix-en-Provence, France). RESULTS: Oral airflow was significantly greater in
      patients with poor perceptual results than in patients with good perceptual
      results. Jitter and shimmer were not significantly different because of the
      dispersion of the values. Discriminant factorial analysis showed that a
      combination of jitter, shimmer, and oral airflow was able to identify patients
      with good or poor perceptual results in 77% of cases. CONCLUSIONS: Oral airflow
      allows simple, quick, and reliable assessment of the outcome of phonosurgery and
      can be used in everyday clinical practice.

PMID- 10201760
TI  - Mutational analyses of candidate genes in human squamous cell carcinomas.
AB  - OBJECTIVES AND STUDY DESIGN: Squamous cell carcinomas are common malignancies and
      a major cause of mortality. The molecular mechanisms involved in tumorigenesis
      remain largely unknown, but sequence alterations have been identified in coding
      regions of several genes. Primary squamous cell carcinomas of various tissues
      (skin, head and neck, esophagus, lung, penis, uterus, and vagina) from 52
      patients were analyzed for the presence of mutations within several candidate
      genes presumably involved in tumorigenesis: Gsalpha, Gi2alpha, GTPase activating
      protein (GAP), and patched (PTCH) genes. METHODS: Mutational analysis scheme
      included polymerase chain reaction (PCR), denaturing gradient gel electrophoresis
      (DGGE), single stranded conformational polymorphism (SSCP), and selected sequence
      analysis. RESULTS AND CONCLUSION: No tumor had any evidence of mutations in any
      of these analyzed genes. Mutations within these genes do not occur frequently in
      an unselected population of patients with squamous cell carcinomas.

PMID- 10201762
TI  - Topical antibiotic therapy for recalcitrant sinusitis.

PMID- 10201763
TI  - Injection sucker for nasal surgery.

PMID- 10201761
TI  - Granisetron, droperidol, and metoclopramide for preventing postoperative nausea
      and vomiting after thyroidectomy.
AB  - OBJECTIVES/HYPOTHESIS: Patients undergoing thyroidectomy may be especially at
      risk of experiencing postoperative nausea and vomiting (PONV). This study was
      undertaken to compare the efficacy and safety of granisetron, droperidol, and
      metoclopramide for preventing PONV after thyroidectomy. STUDY DESIGN: Prospective
      randomized, double-blind study. METHODS: One hundred twenty female patients
      received granisetron 40 microg/kg, droperidol 20 microg/kg, or metoclopramide 0.2
      mg/kg (n = 40, each) intravenously (IV) immediately before the induction of
      anesthesia. A standardized general anesthetic technique was employed throughout
      the procedure. RESULTS: The incidence of a complete response, that is, no PONV
      and no need for another rescue antiemetic during the first 3 hours (0 to 3 hours)
      after anesthesia was 90% with granisetron, 55% with droperidol, and 50% with
      metoclopramide, respectively; the corresponding incidence during the next 21
      hours (3 to 24 hours) after anesthesia was 85%, 50%, and 45% (P<.05; overall
      Fisher's Exact probability test). No clinically important adverse events were
      observed in any of the groups. CONCLUSIONS: Prophylactic therapy with granisetron
      is superior to droperidol or metoclopramide for preventing PONV after
      thyroidectomy.

PMID- 10201764
TI  - Creation of large maxillary sinus ostium: a modified antrostomy technique
      removing palatine bone for improved patency.

PMID- 10201765
TI  - Dornhoffer ossicular replacement prosthesis.

PMID- 10201766
TI  - Glutamine.

PMID- 10201767
TI  - Thyroid surgery and the recurrent laryngeal nerve.

PMID- 10201768
TI  - Interstitial laser coagulation for hepatic tumours.
AB  - BACKGROUND: The potential role of interstitial laser coagulation (ILC) for
      patients with irresectable hepatic tumours is currently being investigated. Since
      its introduction in 1983 it has evolved into an innovative minimally invasive
      technique. METHODS: On the basis of a Medline literature search and the authors'
      experience, the principles, current state and prospects of ILC for hepatic
      tumours are reviewed. RESULTS: Animal studies and early clinical studies have
      shown the safety and feasibility of ILC. The site of interest can be approached
      at laparoscopy or percutaneously and treatment is easily repeatable. Recent
      advances include the use of fibres with a cylindrical diffusing light-emitting
      tip, the length of which is adaptable to tumour diameter, water-cooled fibre
      systems, simultaneous multiple fibre application, and hepatic inflow occlusion
      during laser treatment. ILC allows complete destruction of tumours up to 5 cm in
      diameter. Currently a limitation is the lack of reliable real-time monitoring of
      laser-induced effects but progress in magnetic resonance imaging techniques
      should allow accurate temperature measurements to be obtained rapidly during
      treatment. However, the actual benefit of ILC in terms of patient survival
      remains to be investigated. CONCLUSION: In terms of tools and experience, ILC has
      now been developed sufficiently to study its effect on survival of patients with
      irresectable hepatic tumours.

PMID- 10201769
TI  - Experimental techniques and models in the study of the development and treatment
      of abdominal aortic aneurysm.
AB  - BACKGROUND: It is still unclear what initiates aneurysmal dilatation and what
      determines whether or not an aneurysm will continue to expand and rupture. Early
      detection and operative repair of an abdominal aortic aneurysm (AAA) still
      remains the only effective means of reducing the high mortality rate associated
      with the condition. Endovascular techniques are being developed in an attempt to
      reduce the mortality rate associated with elective repair. A variety of animal
      models and experimental techniques have been described in the investigation of
      the pathophysiology of AAA and in the development of improved endovascular
      surgical and pharmacological therapies. This article discusses these models and
      techniques, their advantages and some of the problems encountered in
      extrapolating experimental findings to the human condition. METHODS: This review
      is based on a search of the Medline database from 1966 to March 1998 using
      recognized key words and text words. A further search was then conducted on
      references quoted within selected relevant publications. RESULTS AND CONCLUSION:
      Treatment of rodent aortas with intraluminal elastase or periaortic calcium
      chloride creates reproducible aneurysms that have certain similarities to the
      human pathology; such aneurysms have been favoured in the investigation of the
      pathophysiology of aneurysm expansion. However, these models lack several of the
      prominent features of the human lesion, such as atherosclerosis and intraluminal
      thrombosis. The development of gene knockout mice may lead to a more analogous
      aneurysm formation, with associated atherosclerosis. Many large animal models
      have been used in the development of endovascular techniques but, in general,
      these do not mimic the human pathophysiology and fail to predict medium- and long
      term complications.

PMID- 10201770
TI  - Randomized clinical trial of laparoscopic versus open inguinal hernia repair.
AB  - BACKGROUND: Several studies have suggested that better results are obtained after
      laparoscopic repair of inguinal hernia than after conventional operation. This is
      most obvious for bilateral and recurrent hernias but less accepted for primary
      unilateral hernias. METHODS: This was a randomized clinical trial comparing
      transabdominal preperitoneal laparoscopic repair with the Shouldice technique in
      patients with primary unilateral hernia. Some 138 patients were randomized to
      laparoscopic hernia repair and 130 to open surgical repair. RESULTS: The
      complication rates in the two groups were similar. In the laparoscopic group the
      patients returned to work more rapidly with a median time of 13 versus 18 days (P
      < 0.005) and had a shorter period of analgesia intake with a median time of 2.1
      versus 2.7 days (P < 0.02). The follow-up was 97.8 per cent complete. At a median
      of 12 months, four recurrences (2.9 per cent) were detected in the laparoscopic
      group and three (2.3 per cent) in the open group. CONCLUSION: This study shows
      that in patients with a primary unilateral hernia laparoscopic repair results in
      less postoperative pain and a quicker recovery than open repair.

PMID- 10201771
TI  - Survey of antibiotic prophylaxis in acute pancreatitis in the UK and Ireland.
AB  - BACKGROUND: Current surgical practice with regards to antibiotic prophylaxis in
      acute pancreatitis in the UK and Ireland was overviewed. METHODS: The 1103
      members of the Association of Surgeons of Great Britain and Ireland were surveyed
      by postal questionnaire. A total of 528 replies were received (48 per cent).
      Following exclusion of surgeons not treating patients with acute pancreatitis,
      analysis was carried out on 429 replies. RESULTS: Respondents treated a median of
      12 (interquartile range (i.q.r.) 10-20) patients per year with acute
      pancreatitis. Prophylactic antibiotic therapy was used by 88 per cent of
      responding surgeons, of whom 24 per cent used it in all cases. For surgeons
      professing selective use of antibiotics, the most common indication for use was
      in patients with prognostically severe disease. A cephalosporin was prescribed in
      72 per cent of patients; cefuroxime was the single most common antibiotic.
      Combination therapy with metronidazole was used in 48 per cent of attacks. The
      median duration of antibiotic therapy was 5 (i.q.r. 5-7) days. An adverse drug
      reaction attributable to the use of prophylactic antibiotics was reported by 11
      per cent of respondents. CONCLUSION: This study has established that a
      significant body of clinicians charged with the responsibility of treating acute
      pancreatitis use antibiotic prophylaxis in the initial treatment of patients with
      predicted severe disease.

PMID- 10201772
TI  - Dietary intake after pancreatectomy.
AB  - BACKGROUND: Nutritional intake after pancreatectomy may be impaired. The extent
      of the problem and the effect on intake of specific nutrients is unknown.
      METHODS: A 1-week weighed dietary food intake (using digital scales and a food
      diary) was studied in 15 patients, a median of 4 (range 1-30) months after
      pancreatectomy. Results were expressed as a percentage of estimated average
      requirement (EAR), reference nutrient intake (RNI) or lower RNI (LRNI) values.
      RESULTS: The median energy intake was 1914 (range 1154-2804) kcal/day,
      representing a median of 88 (56-154) per cent of EAR. Fat intake was low (72 (60
      123) g/day); protein intake was adequate (139 (99-219) per cent of RNI).
      Deficiencies were observed in the intake of vitamin D (17 (6-56) per cent of
      LRNI) and, in some patients, selenium (107 (19-203) per cent of LRNI).
      CONCLUSION: Nutritional intake in the months after pancreatectomy could be
      improved by increasing fat intake (with enzyme supplements as appropriate). This
      7-day study also suggests that these patients may require vitamin D and possibly
      selenium supplementation.

PMID- 10201773
TI  - Liver metastases after curative resection in patients with distal bile duct
      cancer.
AB  - BACKGROUND: Curative resection cannot ensure long-term survival for patients with
      distal bile duct cancer. The aim of this study was to determine the most frequent
      mode of recurrence after curative resection and to analyse its risk factors.
      METHODS: Clinical details for 64 consecutive patients with distal bile duct
      cancer who underwent surgical resection between 1980 and 1997 were reviewed.
      Modes of recurrence and clinicopathological findings were analysed based on the
      residual tumour (R) classification. RESULTS: The overall actuarial 5-year
      survival rate was 32 per cent. Of 42 patients undergoing R0 resection 10 were
      alive at 5 years, of 17 having R1 resection one was alive at 5 years, and none of
      the five patients having R2 resection survived for 5 years (R0 versus R1, P =
      0.02). In the R0 group, the incidence of liver recurrence (14 of 42 patients) was
      similar to that in the R1 resection group (six of 17), although there were fewer
      lymph node and peritoneal recurrences than in patients who had R1 resection (P <
      0.05). The high-risk factor for liver metastasis was microscopic vascular
      involvement. Important factors for survival were lymph node metastasis,
      microscopic vascular involvement and age. In addition, microscopic vascular
      involvement was the only independent factor for survival in the R0 group.
      CONCLUSION: R0 resection provided significant survival benefit but had no effect
      on liver recurrence. Therefore, new agents or strategies to prevent liver
      metastasis are necessary for improvement of survival.

PMID- 10201774
TI  - Factors influencing survival of patients undergoing hepatectomy for colorectal
      metastases.
AB  - BACKGROUND: The extent of surgical margin is still a matter of controversy with
      regard to outcome after liver resection for metastatic disease. The aim of this
      study was to clarify the significant prognostic factors after hepatectomy for
      colorectal metastases, with special reference to the surgical margin. METHODS:
      Ninety-six patients who underwent initial hepatic resection for liver metastases
      from colorectal cancer between 1992 and 1994 were studied. RESULTS: Overall 1-, 3
      and 5-year survival rates were 94, 61 and 51 per cent respectively. All of the
      independent factors associated with poor prognosis after hepatic resection were
      tumour-related factors, such as the number of tumours (four or more), presence of
      portal vein invasion, hepatic vein invasion and absence of a fibrous
      pseudocapsule. A positive resection margin was not an independent prognostic
      factor, because of its strong relationship with the number of tumours resected.
      CONCLUSION: A generous surgical margin is not essential for curative hepatic
      resection, although positive surgical margins should be avoided. New potential
      risk factors which affect survival, such as the presence of portal vein or
      hepatic vein invasion and the absence of a pseudocapsule, may be helpful for
      defining the indications for postoperative adjuvant treatment.

PMID- 10201775
TI  - Effect of exercise on calf muscle pump function in patients with chronic venous
      disease.
AB  - BACKGROUND: Musculoskeletal dysfunction may be associated with poor calf muscle
      pump function in patients with chronic venous ulceration. The aim of this study
      was to evaluate the effects of physical exercise on calf muscle pump function.
      METHODS: Twenty patients were recruited into a 6-week intensive exercise
      programme. Calf muscle function and calf muscle pump function were assessed using
      an isokinetic device and air plethysmography respectively, before and after the
      exercise programme. RESULTS: There was significant improvement in calf muscle
      pump function, measured as increased ejection fraction and decreased residual
      fraction (P < 0.05); however, venous reflux was not altered (P > 0.05). Calf
      muscle strength and endurance parameters all increased, but not significantly (P
      > 0.05). CONCLUSION: Poor calf muscle pump function in patients with chronic
      venous ulceration can be improved by physical exercise.

PMID- 10201776
TI  - Quantitative study of capillary density in the skin of the foot in peripheral
      vascular disease.
AB  - BACKGROUND: The aim of this study was to investigate possible differences in
      capillary density of the skin of the foot between normal subjects and patients
      with peripheral vascular disease. METHODS: Using in vivo video microscopy, a
      method was developed to measure the average capillary density (ACD) of the skin
      of the foot and toes. In a cross-sectional observational study, 21 patients with
      intermittent claudication and 23 patients with rest pain or ischaemic ulceration
      were compared with 19 age- and sex-matched controls. RESULTS: Mean(s.e.m). values
      of ACD of the foot were 33.7(1.9) and 34.4(1.7) per mm2 in the right and left
      sides respectively for controls, 31.2(1.8) per mm2 (P not significant) and
      31.9(2.6) per mm2 (P not significant) in the symptomatic and contralateral sides
      respectively for patients with claudication, and 22.0(1.8) per mm2 (P < 0.001)
      and 24.3(1.7) per mm2 (P < 0.001) in the symptomatic and contralateral sides
      respectively for patients with rest pain or ulceration. CONCLUSION: Capillary
      density of the skin of the foot is significantly reduced in patients with
      arterial ulceration compared with that in patients with claudication and healthy
      subjects.

PMID- 10201777
TI  - Primary myocutaneous flap closure following resection of locally advanced pelvic
      malignancies.
AB  - BACKGROUND: Perineal wounds, created at the time of extended resection for
      locally advanced malignancy and following chemoradiation, are at risk of serious
      complications. METHODS: To determine whether immediate myocutaneous flap closure
      prevents complications, 57 patients treated with multimodality therapy and
      proctectomy (35 perineal wounds) or sacrectomy (22 posterior wounds) were
      studied. Patients were categorized according to whether they underwent primary
      skin and pelvic closure (group 1; ,n = 20); primary skin and omental pelvic
      closure (group 2; n = 24); or immediate myocutaneous flap closure (group 3; n =
      13). RESULTS: Groups were similar with respect to age and sex; however, group 1
      had more primary tumours and required less radical surgery and chemoirradiation
      than groups 2 and 3. Groups 1 and 2 experienced more complications overall (eight
      of 20, nine of 24 and three of 13 patients in groups 1, 2 and 3 respectively),
      more acute wound complications (seven of 20, nine of 24 and two of 13), delayed
      wound healing (three of 20, six of 24 and one of 13) and more reoperations for
      perineal wound problems (five of 20, seven of 24 and zero of 13). Patients in
      group 2 had a significantly longer hospital stay than those in group 1. Flap
      closure (group 3) did not increase the length of stay. The routine use of primary
      flap closure reduced overall wound complications (eight of 31 versus ten of 26
      patients) and length of hospitalization (13 versus 17 days). CONCLUSION: Complete
      wound healing was achieved in all patients; however, immediate myocutaneous flap
      closure reduced the need for readmission and reoperation.

PMID- 10201778
TI  - Identification of patients likely to benefit from biofeedback for outlet
      obstruction constipation.
AB  - BACKGROUND: Biofeedback for outlet obstruction constipation has a varying success
      rate. The aim of this study was to identify which patients are likely to respond
      to biofeedback. METHODS: Thirty patients with severe outlet obstruction
      constipation were treated by a specialist nurse using three or four sessions of
      visual and auditory feedback of anal sphincter pressures. All patients were
      assessed by evacuating proctography, whole-gut transit studies and anorectal
      physiology before treatment. RESULTS: Two patients did not complete the course of
      biofeedback. Nine patients improved. Before treatment these patients had
      predominantly normal anorectal physiology and were all able to open the anorectal
      angle at evacuating proctography. Nineteen patients did not improve, of whom only
      three had no measured abnormality other than inability to empty the rectum. Ten
      of these patients had abnormal anorectal physiology which may have been due to
      previous vaginal delivery. CONCLUSION: Biofeedback for outlet obstruction
      constipation is more likely to be successful in patients without evidence of
      severe pelvic floor damage.

PMID- 10201779
TI  - Prospective comparison of endosonography, magnetic resonance imaging and surgical
      findings in anorectal fistula and abscess complicating Crohn's disease.
AB  - BACKGROUND: Endosonography and magnetic resonance imaging (MRI) are promising
      methods for evaluating perineal and anorectal fistulas or abscesses. The aim of
      this study was to compare the results of anal endosonography (AES), MRI and
      surgical exploration in the assessment of anorectal fistula or abscess
      complicating Crohn's disease. METHODS: Twenty-two patients with Crohn's disease,
      seven men and 15 women of mean age 38 (range 17-67) years, were included in this
      prospective study. All patients underwent AES (linear probe 7 MHz), MRI and
      operative assessment. RESULTS: AES and MRI demonstrated 14 and nine abscesses
      respectively, whereas 11 abscesses were confirmed by surgical exploration in ten
      patients. The sensitivity of AES and MRI as means of evaluating anorectal
      abscesses was 100 and 55 per cent respectively. The agreement per patient was 86
      per cent (19 of 22) for AES and 59 per cent (14 of 22) for MRI. AES and MRI
      demonstrated 26 and 14 fistulas respectively, whereas 27 fistulas were confirmed
      during surgical exploration in 16 patients. The sensitivity of AES and MRI was 89
      and 48 per cent respectively. The level of agreement per patient was 82 per cent
      (18 of 22) for AES and 50 per cent (11 of 22) for MRI. CONCLUSION: AES with a
      linear probe is more accurate than MRI in detecting anorectal abscesses
      complicating Crohn's disease, and much more accurate in the evaluation of complex
      fistulas.

PMID- 10201780
TI  - Three-dimensional endoanal sonography in assessing anal canal injury.
AB  - BACKGROUND: Instrument design limits endosonography of the anal canal to the
      axial plane, with no capability for longitudinal imaging or measurement. Using
      three-dimensional reconstructions, the relationship between the radial and linear
      extent of an anal sphincter tear has been explored, and sex differences in anal
      canal and sphincter length have been established. METHODS: Three-dimensional
      reconstructions were performed in 20 controls and 24 patients with faecal
      incontinence found to have 25 external and five internal sphincter defects. The
      radial and linear extent of any sphincter tear was measured. In controls the
      length of the sphincters was compared with the total anal canal length, and the
      maximum and mean internal sphincter thickness was compared. RESULTS: The radial
      angle of an internal or external sphincter defect was significantly related to
      its length (R2 = 96.8 per cent and R2 = 84.4 per cent respectively; both P <
      0.001). The anal canal was longer in men than in women (mean(s.d.) 32.6(5.3)
      versus 25.1(3.4) mm; P < 0.001). The internal anal sphincter was also longer in
      men (25.6(6.3) versus 19.8(4.0) mm; P < 0.02), but the mean internal sphincter
      length as a percentage of total anal canal length did not differ (78.3 versus
      78.7 per cent; P not significant). The anterior external anal sphincter was
      longer in men than in women (32.6(5.3) versus 15.3(2.8) mm; P < 0.001), and
      formed a greater percentage of total anal canal length (100 versus 62.9 per cent;
      P < 0.001). CONCLUSION: Multiplanar imaging has revealed a direct relationship
      between the length of a sphincter tear and its radial extent as shown on axial
      scanning. Marked sex differences in sphincter configuration have been
      demonstrated. In women the shorter anterior sphincter length highlights the risk
      of complete sphincter disruption with extensive tears.

PMID- 10201781
TI  - Intraobserver and interobserver agreement in anal endosonography.
AB  - BACKGROUND: The aim of this study was to determine intraobserver and
      interobserver agreement for sonographic measurements of anal canal structures
      using anal endosonography (AES), and to determine interobserver agreement for the
      diagnosis of anal sphincter disruption. METHODS: Fifty-one consecutive patients
      referred for AES for the investigation of possible sphincter abnormality were
      examined. Studies were reviewed by two observers who measured anal canal
      structures at defined levels and locations, and recorded an opinion on sphincter
      integrity. Repeated measurements made by each observer were compared to determine
      intraobserver agreement, and measurements and diagnoses were compared between
      observers to determine interobserver agreement. RESULTS: Intraobserver agreement
      was better than interobserver agreement for measurements of anal canal
      structures. Interobserver limits of agreement for external sphincter measurements
      spanned 5 mm, whereas those for the internal sphincter spanned 1.5 mm.
      Interobserver agreement for diagnosis of sphincter disruption and internal
      sphincter echogenicity was very good (kappa = 0.80 and 0.74 respectively).
      CONCLUSION: The limits of agreement for intraobserver and interobserver
      measurements of anal canal structures on AES have been defined. Interobserver
      assessment of sphincter disruption is very good.

PMID- 10201782
TI  - Rectal examination in paediatric surgical practice.

PMID- 10201783
TI  - Changing strategy for rectal cancer is associated with improved outcome.
AB  - BACKGROUND: In 1980, surgery for rectal cancer at the Department of Surgery,
      Uppsala University Hospital was concentrated to a colorectal unit and a more
      systematic use of adjuvant radiotherapy began. In 1985, total mesorectal excision
      was introduced. The aim of this study was to determine whether these changes had
      an impact on the overall treatment outcome. METHODS: Some 423 consecutive
      patients with rectal cancer had surgery between 1974 and 1995 and were followed
      up until 1 January 1998. Outcome analysis was made according to the following
      predefined intervals of diagnosis: 1974-1979, 1980-1984 and 1985-1995. RESULTS:
      The overall local recurrence rate was 47 per cent in the first interval, and 13
      and 11 per cent during the second and third respectively (P < 0.001). In the
      third interval, of 119 patients who received preoperative irradiation and
      underwent radical resection, only three (3 per cent) had locally recurrent rectal
      cancer. There was improved cancer-specific survival between the first and the
      last intervals of the study (P = 0.03). CONCLUSION: These data are consistent
      with the interpretation that the results of treatment can be improved by
      concentration of surgery to a colorectal team.

PMID- 10201784
TI  - Surgical implications of underestimation of adrenal tumour size by computed
      tomography.
AB  - BACKGROUND: Size of adrenal mass is an important consideration during adrenal
      surgery, with regard to the choice of surgical approach and management of
      adrenaloma. The aim of the present study was to evaluate the precision of
      preoperative computed tomography (CT) on the size estimation of adrenal lesions
      and to review its potential implications on surgical decision making. METHODS:
      Records of 110 patients who underwent adrenalectomy for various adrenal
      pathologies from 1981 to 1997 were reviewed retrospectively. Patients (n = 92)
      who had documented dimensions of adrenal mass by both preoperative CT and
      pathological examination were selected for analysis. RESULTS: CT overall
      underestimated the actual size of adrenal lesions by 16 per cent compared with
      measurement of resected specimens (mean 3.1 versus 3.6 cm; P < 0.001). There was
      a significant underestimation of the actual size of adrenal lesions measuring
      less than 6 cm by CT but not for lesions larger than 6.0 cm. Phaeochromocytoma (n
      = 17) was the only pathological condition consistently underestimated by CT.
      CONCLUSION: Conventional CT overall underestimates the real size of adrenal
      lesions, in particular phaeochromocytoma and adrenal tumours of less than 6.0 cm
      in size. Surgical decision making based on size should take this limitation into
      account.

PMID- 10201785
TI  - Effect of training on the incidence of nerve damage in thyroid surgery.
AB  - BACKGROUND: In thyroid surgery early postoperative recurrent laryngeal nerve
      (RLN) dysfunction offers a sensitive measure of the quality of the operation. The
      aim of this study was to analyse the effect of training in thyroid surgery on the
      rate of early functional disturbances of the RLN after thyroid resection.
      METHODS: In 617 patients (median age 48 years, female to male ratio 2.8:1) who
      underwent unilateral or bilateral thyroid resection, 1059 RLNs were subjected to
      operative risk. Laryngoscopy was performed before and after operation. The 45
      surgeons were divided into three groups: group 1, specialist thyroid surgeons;
      group 2, experienced surgeons; and group 3, residents. Personal gain of
      experience was defined by the preceding number of thyroid operations. Within each
      group the complication profile was determined by adding the personal complication
      profiles of each surgeon. RESULTS: The complication rates were low during
      surgical residency (group 3). In group 2 complication rates increased up to the
      50th operation. Group 1 showed the expected exponential decrease to under  per
      cent after another 130 operations. CONCLUSION: Complication rates are affected
      considerably by the extent of surgical experience in a non-linear and complex
      logarithmic manner, starting with low rates in the beginner group, peaking after
      further experience and then decreasing exponentially.

PMID- 10201786
TI  - Accuracy of intraoperative frozen-section analysis of axillary nodes. Edinburgh
      Breast Unit team.
AB  - BACKGROUND: Intraoperative assessment of axillary lymph node involvement would
      allow selection of patients who would benefit from axillary lymph node
      dissection. METHODS: Eighty-eight patients undergoing mastectomy or wide excision
      had four nodes sampled and sent for frozen-section examination. RESULTS: Frozen
      section analysis of the nodes was correct in 81 of the 88 patients but missed
      seven of the 26 patients who had involved nodes on paraffin section (sensitivity
      73 per cent). CONCLUSION: Frozen-section analysis of axillary lymph nodes as
      currently practised cannot be recommended for routine use although it may have a
      role in specific groups of patients.

PMID- 10201787
TI  - Factors leading to local recurrence or death after surgical resection of
      phyllodes tumours of the breast.
AB  - BACKGROUND: Local recurrence and death from metastases are occasional, but
      consistent, themes in reports of patients with phyllodes tumours. Factors that
      might contribute to these outcomes were sought. METHODS: Data from 38 patients
      with a phyllodes breast tumour were reviewed retrospectively, reclassifying the
      pathological material using the Pietruszka and Barnes criteria. RESULTS: At a
      median of 12 months, nine patients had developed a local recurrence and four had
      died from metastases. Following local excision in 24 patients (for diagnosis in
      13, for 'fibroadenoma' in nine and for phyllodes tumour in two patients), 13 had
      no further surgery and five had local recurrence (three of eight benign tumours,
      two of two malignant tumours). Wide local excision or mastectomy in 18 patients
      was followed by four recurrences (one of eight borderline tumours, three of ten
      malignant tumours). All patients with recurrence had margin involvement on
      histological examination, but not all patients with margin involvement developed
      recurrence. Lack of statistical correlation between local recurrence and age,
      delay, size, grade or type of surgery was confounded by selection bias for more
      extensive surgery for malignant tumours. Death correlated with size (P = 0.05)
      and grade (P = 0.03) of tumour. CONCLUSION: Inadequate preoperative diagnosis
      ('fibroadenoma' or failure of triple assessment) frequently led to local excision
      with positive margins. Without revision this often resulted in local recurrence.
      Local recurrence of any grade was usually followed by further recurrence. Death
      was related to tumour size and histological grade, confirming these as prognostic
      factors.

PMID- 10201788
TI  - Experimental study of the effect of intraperitoneal heparin on tumour
      implantation following laparoscopy.
AB  - BACKGROUND: Conclusions drawn from clinical reports of port site metastases
      following laparoscopic resection of intra-abdominal malignancy are now supported
      by a burgeoning experimental literature which suggests that laparoscopy promotes
      tumour metastasis to wounds. This study investigated the effect of
      intraperitoneal blood and heparin on the incidence of tumour cell implantation
      and port site metastasis. METHODS: Twenty-four Dark Agouti rats underwent
      laparoscopy with carbon dioxide insufflation and the instillation of a tumour
      cell suspension and/or blood into the peritoneal cavity. Rats were allocated
      randomly to one of the following study groups (six rats per group): (1) controls;
      (2) intraperitoneal blood (2 ml blood introduced from a syngeneic donor rat); (3)
      intraperitoneal heparin; (4) intraperitoneal blood and heparin. Rats were killed
      7 days after the procedure, and the peritoneal cavity and port sites were
      examined for the presence of tumour. RESULTS: Tumour implantation and port site
      metastases were reduced by the intraperitoneal administration of heparin, but
      increased by the presence of intraperitoneal blood. CONCLUSION: The results of
      this study suggest that tumour implantation following laparoscopy is promoted by
      the presence of intraperitoneal blood and that this effect may be reduced by the
      use of intraperitoneal heparin.

PMID- 10201789
TI  - Mechanism of action of antireflux procedures.
AB  - BACKGROUND: To define the clinical role of antireflux surgical procedures a
      proper understanding of their mode of action is required. The aim of this study
      was to investigate the impact of total or posterior partial fundoplication on the
      function of the lower oesophageal sphincter (LOS) in the basal state as well as
      during stimulation. METHODS: Patients with chronic reflux (n = 24) were
      randomized either to a total fundic wrap or to a posterior partial (Toupet)
      fundoplication. Basal LOS function was investigated as well as the response to
      inhibitory stimuli 4 years after operation. Inhibitory stimulation was elicited
      by water swallows and by gas distension (750 ml air insufflation into the
      stomach). RESULTS: Basal LOS tone was substantially higher (P = 0.01) after a
      total than a partial wrap, as was the nadir pressure after water swallows (10.1
      versus 3.4 mmHg). Body position did not affect this difference. Transient LOS
      relaxations occurred only occasionally in the basal state. The frequency of
      transient LOS relaxation increased somewhat during the first 10 min of stomach
      distension with more occurring in patients who underwent a Toupet procedure.
      Common oesophagogastric cavities were more often seen in this latter group of
      patients after gas distension of the stomach. CONCLUSION: These physiological
      observations on the LOS after total and posterior partial fundoplication explain
      the observed clinical differences in favour of the latter operation. The partial
      fundoplication seems to restore the physiology of the gastro-oesophageal junction
      more adequately, allowing air to be vented from the stomach without jeopardizing
      the antireflux barrier.

PMID- 10201791
TI  - Informed consent in patients with acute abdominal pain.

PMID- 10201790
TI  - Inhibition of platelet-activating factor, intercellular adhesion molecule 1 and
      platelet endothelial cell adhesion molecule 1 reduces experimental pancreatitis
      associated gut endothelial barrier dysfunction.
AB  - BACKGROUND: Endothelial barrier dysfunction is a critical link in the development
      of tissue injury and organ dysfunction, via upregulation and exposure of adhesion
      molecules, intercellular signals and leucocyte-endothelial cell interactions.
      Inhibitors of inflammatory mediators and receptors have been suggested as a means
      of downregulating the cascade of both local and systemic inflammation. METHODS:
      The potential therapeutic inhibition of platelet-activating factor (PAF),
      intercellular adhesion molecule (ICAM) 1 and platelet endothelial cell adhesion
      molecule (PECAM) 1 was investigated in pancreatitis-associated gut endothelial
      dysfunction in rats, by treatment with a PAF antagonist (lexipafant, BB-882) and
      monoclonal antibodies against rat ICAM-1 (anti-ICAM1-Mb) and PECAM (anti-PECAMA1
      Mb). Alterations in gut endothelial barrier dysfunction and leucocyte
      recruitment, and systemic levels of interleukins were evaluated. RESULTS: Plasma
      exudation measured by the albumin leakage index and tissue leucocyte recruitment
      in the distal small intestine and colon increased significantly 12 h after
      induction of pancreatitis and treatment with saline. These alterations were to
      varying degrees counteracted by treatment with lexipafant, anti-ICAM1-Mb or anti
      PECAM1-Mb. Alterations in levels of interleukin (IL) 1 paralleled the changes in
      gut endothelial barrier dysfunction and leucocyte trapping. CONCLUSION: Treatment
      with lexipafant and monoclonal antibodies against ICAM-1 or PECAM-1 reduced the
      severity of pancreatitis-associated gut endothelial dysfunction, and decreased
      systemic concentrations of IL-1 and local leucocyte recruitment.

PMID- 10201792
TI  - Informed consent in patients with acute abdominal pain.

PMID- 10201793
TI  - Current surgical practice in screening for colorectal cancer based on family
      history criteria.

PMID- 10201794
TI  - Diagnosis and conservative management of intrathoracic leakage after
      oesophagectomy.

PMID- 10201795
TI  - Experience with the Mainz modification of ureterosigmoidostomy.

PMID- 10201796
TI  - Nutritional status of HIV-1 seropositive patients in the Free State Province of
      South Africa: anthropometric and dietary profile.
AB  - OBJECTIVE: To evaluate the nutritional intake and status of HIV-1 seropositive
      patients, as well as the relationship between malnutrition and disease stage.
      DESIGN: A cross-sectional study. SETTINGS: The Immunology Clinic at the Pelonomi
      Hospital in Bloemfontein, South Africa. SUBJECTS: Eighty-one HIV/AIDS patients in
      different stages of disease were recruited consecutively from January to May
      1995. Eleven of these patients were followed in 1997. MAIN OUTCOME MEASURES:
      Anthropometric data including current weight, height, triceps skinfold thickness,
      mid-upper-arm circumference, body mass index and bone-free arm muscle area were
      collected. Nutrient intake was estimated using a diet history in combination with
      a standardised food frequency questionnaire. The patients were divided into 3
      groups according to their CD4+ T cell counts. RESULTS: The men were leaner (BMI =
      18.9) than the women (BMI = 22.7) and patients with a CD4+ T cell count < 200
      (stage III) tended to have the lowest median values for all anthropometric
      measurements. More than half the patients had a low intake (< 67% of the
      recommended dietary allowances) of vitamin C, vitamin B6, vitamin D, vitamin A,
      calcium, iron and zinc. CONCLUSIONS: The results confirms that HIV/AIDS patients
      from this population are malnourished. There was, however, no association between
      disease stage and nutritional status. Nutritional supplementation of HIV/AIDS
      patients should be considered, as this might lead to improved immune function in
      these patients.

PMID- 10201797
TI  - Dietary intake of vegetables and fruits among adults in five regions of Spain.
      EPIC Group of Spain. European Prospective Investigation into Cancer and
      Nutrition.
AB  - OBJECTIVE: To assess the consumption of vegetables and fruits (V&F) in adults
      from five regions in Spain according to sex, age and educational level. DESIGN:
      Cross-sectional study within the members of the EPIC cohort in Spain. SETTING:
      Three regions of the north of Spain (Asturias, Guipuzcoa and Navarra) and two
      regions of the south of Spain (Granada and Murcia). SUBJECTS: 41448 healthy
      volunteers (15365 men, 25813 women), aged 29-69 y. INTERVENTIONS: Information on
      habitual diet during the previous year was collected by means of a computerised
      version of a diet history questionnaire. RESULTS: Among men, the mean daily
      consumption of vegetables and of fruits was 273.7 g (3.4 servings) and 348.3 g
      (4.4 servings) respectively. Among women, the corresponding vegetables and fruit
      intakes per day were 244.4g (3.1 servings) and 349.4g (4.4 servings). The total
      V&F intake tended to increase with age and educational level. Overall, 74% of
      subjects consumed 400 g/d (5 servings) of vegetables and fruit. CONCLUSIONS:
      Consumption of vegetables and fruits in healthy adults in Spain is considerably
      higher than in most European countries and the United States; this complies with
      what is considered to be the Mediterranean diet. Despite some regional
      differences, there were no clearly differentiated patterns of V&F intake between
      southern and northern regions within Spain.

PMID- 10201798
TI  - Using obese-specific charts of height and height velocity for assessment of
      growth in obese children and adolescents during weight excess reduction.
AB  - OBJECTIVE: The influence of weight excess reduction on height and height velocity
      of obese subjects should be evaluated on the basis of appropriate standards,
      since the pattern of growth of obese subjects is different from that of normal
      weight subjects. DESIGN, SUBJECTS AND MEASUREMENTS: Height, weight and triceps
      skinfold thickness were recorded from 17987 school subjects (9256 males and 8731
      females), 3-18 y of age, from three provinces of central Italy, and a growth
      reference curve of height was constructed. Using BMI (as computed using the
      tables of Rolland-Cachera et al) and triceps skinfold thickness, normal-weight
      subjects (NWS) and obese subjects (OS) were identified and specific reference
      curves (mean+/-s.d. every sixth month of age) were developed for both groups.
      Centiles of height were also calculated for OS. Various (2-4) measurements of
      height in school subjects were performed and a graph of height velocity (HV) was
      constructed in NWS and in OS using the JPPS method. The yearly mean +/-s.d. of HV
      was also calculated, based on square root transformed data (in order to realise a
      Gaussian distribution), deriving from successive measurements in total subjects,
      in NWS and in OS. The z-scores of height and of the square root of HV were
      calculated in 217 obese subjects (125 males and 92 females) before and during a
      weight excess reduction programme (WERP). Obese subjects in WERP who showed a
      reduction of z-score of BMI were considered as 'responsive'; those who either
      maintained or showed an increase of z-score of BMI were considered as 'non
      responsive'. Obese subjects in WERP were followed for 1-4 y, giving the following
      results: 0-1 y, 142 responsives and 75 non-responsives; 0-2 y, 76 responsives and
      33 non-responsives; 0-3 y, 35 responsives and 30 non-responsives; 0-4 y, 24
      responsives and 18 non-responsives. RESULTS: Compared to NWS, OS showed a
      significantly greater HV in 4-9y males and in 4-8y females, but in older children
      the pubertal spurt was reduced and more precocious. As a result, the height of
      OS, which was greater in 3-13 year-old males and in 3-11.5 year-old females,
      subsequently showed a reduction, as compared to that of NWS, in 16-18 year-old
      males and in 13-18 year-old females. In both responsive and non-responsive groups
      of obese subjects in WERP, the z-scores of height showed a reduction during WERP
      when evaluated using the reference curve of the total school population. In
      contrast, when their growth was evaluated according to the obese-specific
      reference curve, no significant variation was observed comparing both z-scores
      before and during the WERP. CONCLUSIONS: More appropriate information on the
      growth of obese subjects may be obtained when evaluating the height and HV
      according to obese-specific reference standards from the same population of
      origin. Adopting this modality, no significant variation of height resulted
      during WERP in obese children.

PMID- 10201799
TI  - Nutrient intake and iron status of Australian male vegetarians.
AB  - OBJECTIVE: The study was designed to investigate the iron intake and status of
      Australian, male vegetarians aged between 20 and 50 y. DESIGN: Cross-sectional
      comparison of male vegetarians and age/sex matched omnivores. SETTING: Free
      living community subjects. SUBJECTS: 39 ovolactovegetarians, 10 vegans and 25
      omnivores were recruited by local advertisement. OUTCOME MEASURES: A 12-d
      semiquantitative dietary record to assess iron and zinc intake. Iron status was
      assessed by measurement of serum ferritin and haemoglobin concentrations.
      RESULTS: Mean (s.d.) daily iron intakes of both the ovolactovegetarians (20.4
      (7.7) mg/d) and vegans (22.9 (6.2) mg/d), were significantly higher than the
      omnivores' intake of 15.8 (4.5) mg/d. Ovo-lactovegetarians and vegans had
      significantly (P < 0.001 and P < 0.05, respectively) lower serum ferritin
      concentrations than omnivores: mean (s.d.): 64 (46.9), 65 (49.9) and 121 (72.5)
      ng/ml, respectively. Significantly more ovolactovegetarians and vegans than
      omnivores had serum ferritin concentrations below 25 ng/ml and below 12 ng/ml (P
      < 0.05). A higher proportion of omnivores had concentrations above 200 ng/ml (P <
      0.05). The differences in serum ferritin concentrations between the vegetarians
      and omnivores remained significant even after exclusion of iron supplement users.
      CONCLUSION: Australian male vegetarians had iron intakes higher than those of
      omnivores and above recommended levels, but their iron status was significantly
      lower.

PMID- 10201800
TI  - Vitamin D: seasonal and regional differences in preschool children in Great
      Britain.
AB  - OBJECTIVES: To examine seasonality of 25-hydroxyvitamin D (25OH-D) levels in
      British preschool children and the effect of vitamin D supplementation on this.
      DESIGN: The National Diet and Nutrition Survey of children aged 1.5 4.5 y in
      Britain during 1992-3 measured dietary intakes and blood status indices,
      including those for vitamin D, during all four seasons. The present study
      addresses the seasonal dependence of the relation between vitamin D intake and
      status. SETTING: 100 randomly selected postcode sectors throughout Britain, whose
      locations were classified as (a) Scotland; (b) Northern England; (c) Central,
      Wales, South+SW; (d) London+SE. SUBJECTS: Of 1859 whose parents or guardians were
      interviewed, 1675 provided a weighed diet estimate, and blood vitamin D status
      (25OH-D) was measured in 756, with approximately equal numbers in each season.
      RESULTS: Vitamin D status is highly dependent on season: moreover, the relation
      between vitamin D intake and status is also seasonally dependent, being strong in
      the winter and negligible in the summer. During the winter, those children who
      had relatively low 25OH-D concentrations generally were those not receiving
      vitamin D supplements. Vitamin D intakes and supplement use were lower in the
      north than in the south of Britain. CONCLUSIONS: For British preschool children,
      dietary vitamin D is of much greater importance in the winter than in the summer.
      There is evidence of regional inequality, with lesser use of supplements in the
      north. Supplements are needed in the winter, to achieve satisfactory vitamin D
      status and minimise the risk of rickets and of poor bone health, especially in
      high-risk groups.

PMID- 10201801
TI  - Iron status of middle-aged women in five counties of rural China.
AB  - OBJECTIVE: To determine the relationships of dietary iron sources, other dietary
      factors, and lifestyle to iron status among premenopausal and recently
      postmenopausal Chinese women with widely varying regional dietary patterns.
      DESIGN: Cross-sectional. Subjects were interviewed, blood samples were drawn, and
      dietary intakes were measured by a 3-day dietary survey for subjects in the five
      survey counties. SETTING: Rural China. SUBJECTS: About 80 randomly selected
      subjects per county among women aged 32 66 y. MAIN OUTCOME MEASURES: Blood
      hemoglobin, plasma ferritin, and plasma iron. RESULTS: Total iron intake was
      relatively high (15-29 mg/d) compared to developed counties. Heme iron intake was
      negligible in two of the study counties. Overall levels of iron deficiency anemia
      were relatively low in these generally iron-stressed women. There was no clear
      statistical relationship between iron intake and physiological iron status.
      Although several measures of dietary intake (heme iron, dietary calcium, animal
      protein) were correlated with several measures of iron status before adjusting
      for survey county, only dietary animal protein was significantly positively
      correlated with plasma ferritin after adjusting for the possibly confounding
      factor of the survey county (r= 0.15, P = 0.009). Intakes of potential inhibitors
      of iron absorption, such as tea, even in very high amounts, were not correlated
      to iron status. Plasma ferritin was positively correlated with plasma retinol (P
      = 0.024) and cholesterol (P = 0.007). Systemic inflammatory response, as
      indicated by high plasma C-reactive protein levels, was shown to be raised in a
      group of subjects with apparently contradictory high levels of ferritin and low
      levels of hemoglobin (P = 0.03). CONCLUSIONS: Iron nutriture in these areas of
      rural China seemed more related to physiological factors such as inflammatory
      response, menses, plasma vitamin A and cholesterol, than to dietary factors.

PMID- 10201802
TI  - Food intake, serum lipids and amino acids of school children in agricultural
      communities in Japan.
AB  - OBJECTIVE: To investigate the correlation among serum lipids, amino acids and
      diet of children in Japan where the mortality of ischemic heart disease is still
      very low. DESIGN: Cross-sectional study. SETTING: Two towns in Shimane
      prefecture, typical mountainous agricultural communities in the western part of
      the mainland of Japan. SUBJECTS: 514 children (10-15 y) in the communities were
      recruited. RESULTS: The mean cholesterol levels ranged from 3.9 to 4.4 mmol/l for
      boys and from 4.3 to 4.5 mmol/l for girls, and serum cholesterol level fell with
      age in boys. Serum cholesterol level of girls rose once between 11 and 13 y and
      fell gradually. Fish intake was positively correlated with serum omega-3 series
      fatty acids. Milk intake was negatively and soybean intake was positively
      correlated with omega-3/omega-6 series fatty acids ratio. Serum branched-chain
      amino acids were correlated negatively with serum polyunsaturated/saturated fatty
      acids ratio. CONCLUSIONS: Serum cholesterol level of children in agricultural
      communities in Japan has risen, and is probably affected by the change of food
      intake. Promoting the intake of soybean and fish, which are traditional Japanese
      foods, will be important in preventing atherosclerosis and ischemic heart
      disease. Attention should be paid to the relationship between branched-chain
      amino acids level in blood and fatty acids metabolism to verify the mechanism of
      the progress of atherosclerosis.

PMID- 10201803
TI  - Longitudinal changes in radial bone density in older men.
AB  - OBJECTIVE: To examine changes in radial bone density and biochemical status, with
      particular reference to calcium, over 18 months in a group of older men.
      SUBJECTS: Thirty-six healthy men (aged 66 76 y) were recruited to the study
      during July and August, 1993. These men were free-living residents of Edmonton
      who were recruited through local organizations for the retired and semi-retired.
      Data for the younger group of men (age 29-60 y) were taken from a previous study
      conducted in our laboratory. DESIGN: using special-purpose computed tomography
      (gammaCT), trabecular (TBD), cortical (CBD) and integral (IBD) bone densities
      (gm/cm3) were measured in the ultra-distal radius at 6-month intervals over 18
      months. At baseline, and at each subsequent study visit, serum was obtained from
      each subject for determinations of calcium, phosphate, 25-hydroxyvitamin D,
      alkaline phosphatase, and immunoreactive parathyroid hormone. A 24-h urine sample
      was also obtained at each study visit for determination of urinary calcium,
      phosphate and creatinine. RESULTS: In repeated measures analysis of variance of
      the data for the older men serum 25-hydroxyvitamin D was significantly decreased
      (P<0.001) over time, while TBD was increased (+0.60% per year, P<0.01).
      Longitudinal rates of change for TBD, CBD and IBD were: -0.94%, 0.92% and 0.74%
      per year respectively when bone density data at baseline for the older men and
      the historical data for younger men were combined. However, separate analyses of
      the data for the younger and the older men indicated no significant age-related
      changes in bone density for men aged 29-60 y, or for men aged 66-76 y. However,
      differences in TBD, CBD and IBD between the younger and older groups of men were
      significant (P < 0.001). CONCLUSIONS: In a group (n = 36) of older men (mean age
      71.7 y) studied longitudinally over 18 months, bone density in the distal radius
      did not decrease over time. Mean bone density in this group of men was, however,
      significantly (P < 0.001) lower than in a group of younger men (n = 17, mean age
      46.7 y). Regression analysis using cross-sectional bone density data at baseline
      for the older male group, and historical data for the younger male group,
      indicates that bone loss occurs with increasing age at a rate of about 1% per
      year averaged over ages 29-76 y. Bone density variables were not correlated with
      either height or weight, or with any biochemical or hormonal variable measured in
      this study.

PMID- 10201805
TI  - Estimates of mineral intakes using food composition tables vs measures by
      inductively-coupled plasma mass spectrometry: Part 1. calcium, phosphorus and
      iron.
AB  - OBJECTIVES: To examine the accuracy of food composition table (FCT)-based
      estimation of dietary nutrient element intake in reference to the instrumental
      measurement by inductively-coupled plasma mass spectrometry (ICP-MS). DESIGN:
      Cross-sectional study. SETTING: Communities. SUBJECTS: 884 adult non-smoking
      women in 23 study sites in 6 areas in Asia (i.e. China (Mainland), China
      (Taiwan), Korea, Japan, Malaysia and the Philippines. METHODS: 24-hour food
      duplicate samples foods offered by the women were subjected (1) to the estimation
      of daily dietary intake of calcium (Ca), phosphorus (P) and iron (Fe), using 6
      types of national FCTs one for each area, and (2) to ICP-MS analysis for the
      measurement of the same elements. RESULTS: Comparison of the estimated values (E)
      with corresponding measured values (M) in terms of the mean (E)/(M) ratio for
      each area showed that the ratio was various among the 6 areas studied. Ca showed
      smallest deviation (69 to 165%) from the agreement (100%), which was followed by
      P (113 to 306%), whereas Fe showed the largest deviation (124 to 368%).
      CONCLUSIONS: Caution should be exercised in using FCTs for estimation of dietary
      Fe intake. The wide variation was not due to the use of the FCT established for
      each area, because the inter-study site variation within one area was as large as
      the inter-area variation.

PMID- 10201804
TI  - Changes in dietary intake during a 6-year follow-up of an older population.
AB  - OBJECTIVE: To examine prospective changes in food habits and nutrient intakes in
      a representative New Zealand sample of community dwelling adults aged 70 y and
      over. DESIGN: Longitudinal study with food intake data collected in 1988/89 and
      again in 1995/96. In an attempt to distinguish age, time and cohort effects, data
      were analysed longitudinally, cross-sectionally and time-sequentially. SUBJECTS:
      The sample for study consisted of all non-institutionalised people aged 70 years
      and over registered with the Mosgiel Health Centre in 1988. In 1988/89, 678
      adults completed a dietary survey (85% of those eligible) and 248 adults
      participated again in 1995/96 (66% of those eligible). RESULTS: Energy intakes
      declined longitudinally in men only; however, this decline appeared not to be an
      aging effect as energy intake was not found to decrease with age cross
      sectionally. Percentage of energy from protein increased by 0.7% in women (95%
      confidence interval 0.2-1.2) in both the longitudinal and time-sequential
      analysis, suggesting a time effect. The percentage of energy from saturated fat
      decreased 0.7% (95% confidence interval -1.4 to -0.1) and percentage of energy
      from polyunsaturated fat increased 0.4% (95% confidence interval 0.0-0.7) in
      women, and appears to be a time effect. However, the increase in saturated fat
      and decrease in polyunsaturated fat with advancing age seen cross-sectionally
      suggests a cohort effect also occurring. In 1995/96, more people were using
      margarine as a spread and vegetable oils to cook meat. Milk and milk product
      consumption increased (not significantly), and meat intake decreased
      significantly by 5 and 4 servings per month in men and women, respectively. There
      was an increase in the proportion of people who ate breakfast cereal at least
      once a week, and more women ate brown or wholemeal bread in 1995/96. CONCLUSION:
      Over the 6 y follow-up period studied, there was no indication of an age effect
      on nutrient intakes in adults aged 70 y and older; however, the changes occurring
      over time demonstrate that older adults, particularly women, are making changes
      towards healthier food choices.

PMID- 10201806
TI  - Estimates of mineral intakes using food composition tables vs measures by
      inductively-coupled plasma mass spectrometry: Part 2: sodium, potassium,
      magnesium, copper, zinc.
AB  - OBJECTIVES: To examine the accuracy of food composition table (FCT)-based
      estimation of dietary nutrient element intake in reference to the instrumental
      measurement by inductively-coupled plasma mass spectrometry (ICP-MS), as an
      extension of the first part of this study. DESIGN: Cross-sectional study.
      SETTING: Communities. SUBJECTS: 782 adult non-smoking women in 21 sites in 4
      areas [China (Mainland), Japan, Korea and Malaysia] in Asia. METHODS: 24-h food
      duplicate samples offered by the women were subjected 1. to the estimation (E) of
      daily element intake taking advantage of national food composition tables (FCTs)
      and 2. to the measurement (M) by inductively-coupled plasma mass spectrometry
      (ICP-MS). The two sets of the results were compared in terms of the (E)/(M)
      ratio. Because of the limited availability of the element database in the FCTs,
      the comparison on Na and K was possible in the 4 areas, whereas that of Mg, Cu
      and Zn was only in two areas of China (Mainland) and Japan. RESULTS: The (E)/(M)
      ratio was in a relatively narrow range of 75 to 114% in case of Na, and 91 to
      120% for K (with one exception of 201% for K in Malaysia). Correlation
      coefficients between (E) and (M) were statistically significant for both Na and K
      in the 4 areas. In cases of Mg, Cu and Zn, agreements were generally poor, and
      the (E)/(M) ratio was close to 100% only in the cases of Cu and Zn in Japan.
      CONCLUSIONS: In overall evaluation combining the results on Ca, P and Fe in the
      preceding report with the results in the present report on Na, K, Mg, Cu and Zn,
      FCT-based estimation generally did not agree with the measure by ICP-MS. The
      disagreement did not allow precise FCTs-based estimation of dietary intakes of
      these nutrient elements, possibly except for Na.

PMID- 10201807
TI  - Effects of smoking and smoking cessation on dietary habits of a Swiss urban
      population.
AB  - OBJECTIVES: To assess whether current smokers eat differently than never smokers
      and the relation of smoking cessation to dietary change. DESIGN: Population-based
      survey from 1993-1997. SETTING: The Bus Sante 2000, epidemiologic observatory of
      Geneva, Switzerland. SUBJECTS: A representative sample of 2301 men and 2306 women
      resident of Geneva, Switzerland. RESULTS: In both genders, compared to never
      smokers, current heavy smokers (> or = 20 cigarettes/d) consumed daily less total
      vegetables proteins (P <0.03), carbohydrates (P<0.0001), saccharose (P<0.01),
      fibers (P < 0.0001), beta-carotene (P < 0.001), fruit (P < 0.0001) and vegetables
      (P < 0.04), but they drank more alcohol (P < 0.0001) and more coffee (P < 0.005).
      In addition, female current smokers ate less energy (P < 0.4), complex
      carbohydrates (P < 0.002), cereals (P < 0.003), vegetables (P < 0.0001) and less
      iron (P < 0.02). The diet of ex-smokers tended to become more similar to that of
      never smokers. When longer duration of smoking cessation increased, the
      consumption of total carbohydrates and complex carbohydrates increased (P < 0.01
      and P < 0.06), and alcohol decreased (P < 0.07) in both genders. CONCLUSIONS: As
      in other Western countries, the diet of Swiss smokers appears less healthy than
      that of never smokers in both men and women, while smoking cessation has
      beneficial aspect on the quality of the diet. Current smoking appears to have an
      even stronger effect on the diet of women than on the diet of men.

PMID- 10201808
TI  - Diurnal variation in the assessment of body composition using bioelectrical
      impedance in children.

PMID- 10201809
TI  - Effects of additional questions about fat on the validity of fat estimates.

PMID- 10201810
TI  - Immunological localization and ontogenetic development of inhibin alpha subunit
      in rat brain.
AB  - This study examined the immunolocalization and ontogeny of the inhibin-specific
      alpha subunit in the brain of male rats. Immunohistochemistry using antiserum
      directed against the mature region of porcine inhibin alpha (1-19, Tyr20)
      revealed positive reactions in process-bearing cells resembling astroglia in
      several regions, especially in the dorsal region of the third ventricle, medial
      and ventral arcuate nucleus, hippocampal dentate gyrus, and layers 1-3 of the
      cerebral cortex. Generally, inhibin alpha-positive cells in the limbic cortex had
      larger cell bodies and longer processes than those in the hypothalamus. These
      inhibin alpha-positive cells were verified to be positive for glial fibrillary
      acidic protein (GFAP), a differentiated astroglial marker, by double
      immunolabelling. The expression of inhibin alpha mRNA was higher in the brains of
      neonatal rats than in those of adult rats, as revealed by reverse transcription
      competitive polymerase chain reaction, although the similar changes of
      immunoreactive inhibin alpha subunit in the brain was not observed. Orchiectomy
      did not affect expression of inhibin alpha mRNA in the hypothalamic area. This
      study suggests that inhibin-related peptide is produced by differentiated
      astrocytes, especially in the hypothalamic arcuate nucleus, the hippocampal
      dentate gyrus, and the cerebral cortex, and that the expression of inhibin alpha
      is regulated during brain development.

PMID- 10201811
TI  - Leptin receptor and neuropeptide Y gene expression in the sheep brain.
AB  - Leptin, a protein secretory product of adipocytes, is important in appetite
      control, energy balance and reproduction. In rodents, the physiological effects
      of leptin are centrally mediated, in part via the neuropeptide Y (NPY) system in
      the hypothalamus. The role of leptin in ruminants, where appropriate nutrition
      and reproductive status are of major economic concern, is largely unknown. To
      elucidate the function of leptin in sheep we have investigated putative sites of
      action for leptin in the brain and pituitary gland using both in-situ
      hybridization to detect expression of the signalling form of the leptin receptor
      (OB-Rb) and in-vitro autoradiography using (125I)leptin to detect sites of
      specific leptin binding. OB-Rb gene expression occurred in the hippocampus,
      cerebral cortex, preoptic area, stria terminalis and choroid plexus, and within
      the hypothalamus in the paraventricular (PVN), ventromedial (VHM) and arcuate
      (ARC) nuclei. OB-Rb gene expression in the ovine pituitary gland was not detected
      by in-situ hybridization. Sites of OB-Rb and NPY gene expression were compared
      using both in-situ hybridization on adjacent sections containing the arcuate and
      ventromedial nuclei, and dual in-situ hybridization on sections containing these
      areas. In serial sections, OB-Rb expression was found to correspond closely with
      that of NPY over the arcuate nuclei. Using dual in-situ hybridization, NPY
      expressing neurones in the arcuate nuclei were also positive for OB-Rb gene
      expression. Therefore, it appears that leptin may partly act via OB-Rb located on
      NPY neurones in the sheep hypothalamus as in the rodent.

PMID- 10201812
TI  - Detection of melanocortin-3 receptor mRNA in immature rat pituitary: functional
      relation to gamma3-MSH-induced changes in intracellular Ca2+ concentration?
AB  - We have previously shown that gamma3-MSH stimulates DNA replication in
      lactotrophs, somatotrophs and thyrotrophs of early postnatal rat pituitary in
      culture. Since the melanocortin-3 (MC-3) receptor is the only known receptor
      displaying high affinity for gamma3-MSH, the present study explored whether mRNA
      of the latter receptor is present in the pituitary and whether the receptor is
      functional. RT-PCR of RNA extracts from 14-day-old rat pituitary revealed the
      presence of MC-3 receptor mRNA in both the anterior and the neurointermediate
      lobe. The identity of the amplified products was confirmed by sequence analysis.
      Dispersed cells of 14-day-old female rats (24 h in culture) were exposed to
      gamma3-MSH, and changes in intracellular free calcium levels ([Ca2+]i) were
      assessed by means of fluo-3 video imaging. Gamma3-MSH evoked a rapid and
      maintained oscillating [Ca2+]i increase in 5%, 10% and 15% of the cells at a dose
      of 0.1, 1 and 10 nM, respectively. The MC-3/MC-4 receptor antagonist Ac-Nle4
      c[Asp5,(D-Nal(2)7,Lys10]alpha-MSH-(4-10)-NH2 (SHU 9119) blocked the effect of
      gamma3-MSH in about 50% of the responsive cells. The present data suggest that
      the MC-3 receptor is expressed in the rat pituitary but that this receptor
      mediates only half of the effects of its putative ligand, gamma3-MSH, on [Ca2+]i.
      Part of the effect of gamma3-MSH may be mediated by a MC-3 receptor in a
      functional state different from the one studied previously in transfected cell
      lines or by a hitherto unidentified MC receptor.

PMID- 10201813
TI  - Distribution and seasonal variations in levels of three native GnRHs in the brain
      and pituitary of perciform fish.
AB  - Specific and sensitive radioimmunoassays (RIAs) were newly developed for two
      types of gonadotropin-releasing hormone (GnRH), namely, seabream (sb) GnRH and
      chicken (c) GnRH-II. We employed these two RIAs together with a previously
      reported RIA for salmon (s) GnRH to study the presence and regional distribution
      of these three GnRHs in the brains and pituitaries of four perciform fishes (red
      seabream, Pagrus major; black seabream, Acanthopagrus schlegeli; striped
      knifejaw, Oplegnathus fasciatus; and Nile tilapia, Oreochromis niloticus), as
      well as clarify seasonal changes in levels of these GnRHs in the brain and
      pituitary of red seabream. All three GnRHs were found in brains of all fishes
      examined, with regional distributions in the brains of the three GnRHs being
      rather similar. sbGnRH was abundant in telencephalon and hypothalamus. cGnRH-II
      was concentrated from the middle to posterior part of the brain and distributed
      throughout the brain. sGnRH was concentrated in the olfactory bulb and
      distributed all over the brain, as was cGnRH-II. The dominant form of GnRH in the
      pituitary was sbGnRH, with levels 500- to 2400-fold higher than those of sGnRH,
      while cGnRH-II was undetectable in all four species. In the brain and pituitary
      of female red seabream, levels of both brain and pituitary sbGnRH increased from
      October (immature phase) and reached a peak in April (spawning phase), reflecting
      the increase in gonadosomatic index and vitellogenesis. However, levels of sbGnRH
      remained high only in the pituitary of completely regressed fish in June. Levels
      of both sGnRH and cGnRH-II in the brain were higher in the regressed phase and
      remained lower during the spawning phase. From these and previous results, it
      appears that sbGnRH is physiologically the most important form of GnRH in
      reproduction in red seabream and, probably, in other perciforms also.

PMID- 10201814
TI  - Characterization of TSH-positive cells in foetal rat pars tuberalis that fail to
      express Pit-1 factor and thyroid hormone beta2 receptors.
AB  - The thyroid stimulating hormone (TSH)-immunoreactive cells (TSH cells) in the
      pars tuberalis (PT-TSH cell) of the male rat pituitary gland show an intense spot
      like TSH immunoreaction in the paranuclear cytoplasm. However, the ontogenic
      origin and characteristics of these spot-like stained PT-TSH cells remain to be
      elucidated. The present study was designed to investigate the distribution and
      characteristics of PT-TSH cells in the foetal and adult rat pituitary by
      immunostaining for Pit-1 factor and thyroid hormone receptors (TRs) and reverse
      transcriptase-polymerase chain reaction (RT-PCR). TSH cells first appeared in the
      PT at 15.5 days of gestation and were either stained diffusely throughout the
      cytoplasm or displayed a strongly stained, spotty appearance in the paranuclear
      region. By 15.5 days of gestation, the rostral part of the PT consisted of
      columnar epithelium, in which TSH immunoreactivity was spot-like in the apical
      region of cytoplasm corresponding to the Golgi apparatus. At the 16.5 days of
      gestation, TSH cells were present in the pars distalis (PD); however, the cells
      were mostly larger and polygonal with strong staining throughout the cytoplasm.
      These differences between the PT and PD were retained throughout foetal and
      neonatal rat development. The TSH cells in the PD of the adult or gestational rat
      were observed to contain Pit-1 factor by double immunostaining. However, TSH
      cells in the PT lacked Pit-1 factor. RT-PCR confirmed the absence of Pit-1 and
      TRbeta2 mRNA in the PT of the adult and late gestation rat pituitary gland. These
      results suggest that apparently distinct types of TSH cells in the PT develop
      independently from TSH cells in the PD.

PMID- 10201815
TI  - Negative regulation of gonadotropin-releasing hormone and gonadotropin-releasing
      hormone receptor gene expression by a gonadotrophin-releasing hormone agonist in
      the rat hypothalamus.
AB  - There exists evidence for the presence of ultrashort loop feedback circuits of
      gonadotropin-releasing hormone (GnRH) secretion in the hypothalamus. It is,
      however, uncertain whether a similar mechanism is involved in the regulation of
      GnRH gene expression in vivo. Furthermore, little is known about the regulation
      of GnRH receptor (GnRHR) expression in the brain. In the present study, we
      examined the regulation of GnRH and its receptor gene expression by GnRH in vivo.
      A GnRH agonist, [D-Ala6, des-Gly10]GnRH-ethylamide (des-Gly GnRH), was
      administered by intracerebroventricular (i.c.v.) injection via the lateral
      ventricle of ovariectomized and estradiol (OVX + E)-treated rats. The amounts of
      GnRH and GnRHR mRNA were measured in the preoptic area (POA) and posterior
      mediobasal hypothalamus (pMBH) micropunch samples from individual rat brain
      slices by respective competitive reverse transcription-polymerase chain
      reactions. The i.c.v. administration of des-Gly GnRH significantly decreased GnRH
      and GnRHR mRNA expression in a dose-and time-related manner: des-Gly GnRH (6 ng)
      suppressed GnRH and GnRHR mRNA expression within 2 h, and the suppression was
      maintained without significant variation until 8 h after treatment. Treatment
      with Antide, [N-Ac-D-Nal(2)1, pCl-D-Phe2, D-Pal(3)3, Lys(Nic)5, D-Lys(Nic)6,
      Lys(iPR)8, D-Ala10]GnRH (10 ng), a potent GnRH antagonist, did not alter GnRH
      mRNA expression, but prevented des-Gly GnRH-induced suppression of GnRH mRNA
      expression. Antide alone decreased GnRHR mRNA expression, but failed to alter
      agonist-induced suppression of GnRHR mRNA expression. These results demonstrate
      the existence of an ultrashort loop feedback mechanism for GnRH gene expression
      in the POA, along with homologous down-regulation of GnRHR mRNA expression in the
      pMBH.

PMID- 10201816
TI  - Ultrastructural colocalization of vesicular cholecystokinin and corticoliberin in
      the periportal nerve terminals of the rat median eminence.
AB  - Cholecystokinin (CCK) is present in axon terminals distributed around the
      fenestrated capillary loops of the hypothalamo-hypophysial portal system. In the
      hypothalamic paraventricular nucleus, CCK has been shown to coexist with
      corticoliberin (CRH). However, in the median eminence (ME) nothing is known about
      the chemical phenotype of the CCK immunoreactive terminals. This study, carried
      out in the male rat, was designed to examine the possibility of coexistence of
      CCK immunoreactivity (CCK-IR) and CRH-IR in fibres of the ME and to describe, at
      the electron microscopic level, the vesicular pattern of distribution of CCK-IR
      in the pericapillary endings of the ME. The use of the elution-restaining
      procedure showed notable similarities between stainings directed against CCK or
      CRH, respectively, suggesting a colocalization of both peptides in the same
      terminals. This result was confirmed using a simultaneous double-staining
      procedure. At the electron microscope level, double immunogold staining procedure
      enabled us to observe a consistent localization of CCK-IR and CRH-IR over dense
      cored vesicles. Most of the terminals were seen to contain both
      immunoreactivities which, in addition, were often present together in the same
      vesicles. However, some rare endings remained exclusively stained either for CCK
      or for CRH. Our results provide evidence for a concomitant release of CCK and CRH
      into the portal blood.

PMID- 10201817
TI  - Serotonergic innervation of the pituitary pars intermedia of xenopus laevis.
AB  - At this point three brain centres are thought to be involved in the regulation of
      the melanotrope cells of the pituitary pars intermedia of Xenopus laevis: the
      magnocellular nucleus, the suprachiasmatic nucleus and the locus coeruleus. This
      study aims to investigate the existence of a fourth, serotonergic, centre
      controlling the melanotrope cells. In-vitro superfusion studies show that
      serotonin has a dose-dependent stimulatory effect on peptide release (1.6 x basal
      level at 10(-6) M serotonin) from single melanotrope cells. Retrograde neuronal
      tract tracing experiments, with the membrane probe FAST Dil applied to the pars
      intermedia, reveals retrogradely labelled neurones in the magnocellular nucleus,
      the suprachiasmatic nucleus, the locus coeruleus and the raphe nucleus. Of these
      brain centres, after immunocytochemistry only the raphe nucleus revealed
      serotonin-immunoreactive cell bodies. In addition, serotonin-immunoreactive cell
      bodies were found in the nucleus of the paraventricular organ, the posteroventral
      tegmental nucleus and the reticular istmic nucleus. In the pituitary, the pars
      nervosa, pars intermedia and pars distalis all reveal serotonin-immunoreactive
      nerve fibres. With immunocytochemical double-labelling for tyrosine hydroxylase
      and serotonin no colocalization of serotonin and tyrosine hydroxylase was
      observed in cell bodies in the brain, and in the pituitary hardly any
      colocalization was found in the nerve fibres. However, after in-vitro loading of
      neurointermediate lobes with serotonin, tyrosine hydroxylase and serotonin appear
      to coexist in a fibre network in the pars intermedia. On the basis of these data
      we propose that the melanotrope cells in the Xenopus pars intermedia are
      innervated by a 5-HT network originating in the raphe nucleus; this network
      represents the first identified stimulatory input to the pars intermedia of this
      species.

PMID- 10201818
TI  - Peripeduncular lesion alters expression of c-fos induced in the female rat brain
      by male mounting.
AB  - In order to investigate the role of the peripeduncular nucleus (PP) in the
      control of lordosis in female rats, activation of neurons after mounts without
      intromission was investigated by means of FOS immunoreactivity (FOS-IR).
      Ovariectomized rats were injected with estradiol and progesterone and submitted
      to approximately 50 mounts by the male. The vaginal area was covered with masking
      tape to prevent intromission and vaginocervical stimulation. This limited
      stimulation produced FOS-IR in the ventrolateral division of the ventromedial
      hypothalamic nucleus (VMHVL), in the lateral periaqueductal grey (LPAG), in the
      peripeduncular nucleus (PP), and in the posterior intralaminar thalamic nucleus
      (PIL). No significant differences were found in the anterodorsal or posterodorsal
      parts of the medial amygdaloid nucleus, in the medial part of the medial preoptic
      nucleus, in the dorsomedial periaqueductal grey and in the medial division of the
      posterointermediate part of the bed nucleus of the stria terminalis. The same
      experiment was performed in rats with unilateral lesion of the PP. Both VMHVL and
      LPAG activation were significantly reduced in the ipsilateral PP lesion side,
      leading to the conclusion that those structures are primary targets for the
      somatic stimuli that trigger lordotic reflexes and which are relayed in the PP.
      Taking into account what is known about the function of the target structures, it
      is proposed that afferences relayed in the PP reaching the VMHVL would contribute
      to control the long range level of sexual receptivity, whereas stimuli reaching
      the LPAG would serve to control lordotic responses in a moment to moment fashion.

PMID- 10201819
TI  - Differential regulation of hypothalamic tuberoinfundibular dopamine neurones in
      two dwarf rat models with contrasting changes in pituitary prolactin.
AB  - In transgenic growth-retarded (Tgr) rats, expression of human growth hormone
      (hGH) is targeted to hypothalamic GH-releasing hormone (GHRH) neurones. In these
      rats, GHRH is reduced and somatostatin expression is increased, resulting in
      secondary GH deficiency and dwarfism. Tgr rats also show reduced pituitary
      prolactin (PRL), which may reflect an additional lactogenic feedback action of
      the hGH transgene, analogous to that in mice transgenic for peripheral hGH which
      show enhanced dopamine (DA) and tyrosine hydroxylase (TH) expression in the
      hypothalamic tuberoinfundibular dopaminergic (TIDA) neurones that inhibit PRL
      secretion. The present study examined DA histofluorescence and TH
      immunoreactivity in Tgr rats, and also in dw/dw rats, a dwarf strain with primary
      pituitary GH but not PRL deficiency. Radioimmunoassay confirmed a significant
      decrease in total pituitary PRL content in Tgr rats, but showed a marked increase
      in total pituitary PRL in dw/dw rats. Despite their PRL deficiency, Tgr rats
      showed qualitatively increased TIDA histofluorescence and TH immunoreactivity
      compared with AS control rats, though the total number of detectable TH-positive
      TIDA neurones was similar for Tgr and AS. In contrast, dw/dw rats showed
      increased numbers of TH-immunoreactive TIDA neurones whilst TIDA fluorescence was
      unchanged, and these findings were not affected in dw/dw rats given bovine GH
      (200 microg/d s.c. for 7 d). These results suggest that reduced PRL in Tgr rats
      is due to a local lactogenic feedback effect of hGH to stimulate TIDA neurones.
      The complex changes in TIDA neurones probably reflect a combination of increased
      lactogenic feedback in Tgr rats, with an increased (Tgr) or decreased (dw/dw)
      somatogenic feedback on GHRH neurones, some of which coexpress TH. Thus, the
      unchanged number of TIDA neurones in Tgr rats may result from hGH stimulation of
      TH and DA, but a reduction in GHRH-producing cells, whereas increased TIDA
      neurones in dw/dw rats suggests a stimulation by endogenous PRL with an increased
      GHRH cell complement due to GH deficiency. These findings therefore indicate that
      differences in lactogenic feedback in these dwarf rat models are reflected in
      marked differences in their hypothalamic TIDA neurones.

PMID- 10201820
TI  - Enzymatic syntheses of 6-(4H-selenolo[3,2-b]pyrrolyl)-L-alanine, 4-(6H
      selenolo[2,3-b]pyrrolyl)-L-alanine, and 6-(4H-furo[3,2-b]pyrrolyl-L-alanine.
AB  - 6-(4H-Selenolo[3,2-b]pyrrolyl)-L-alanine 1, 4-(6H-selenolo[2,3-b]pyrrolyl)-L
      alanine 2, and 6-(4H-furo[3,2-b]pyrrolyl)-L-alanine 3 have been synthesized via
      reactions of selenolo[3,2-b]pyrrole, selenolo[2,3-b]pyrrole, and furo[3,2
      b]pyrrole, respectively, with L-serine. The reactions are catalyzed by Salmonella
      typhimurium tryptophan synthase.

PMID- 10201821
TI  - Potent, orally absorbed glucagon receptor antagonists.
AB  - The SAR of 2-pyridyl-3,5-diaryl pyrroles, ligands of the human glucagon receptor
      and inhibitors of p38 kinase, were investigated. This effort resulted in the
      identification of 2-(4-pyridyl)-5-(4-chlorophenyl)-3-(5-bromo-2
      propyloxyphenyl)pyrr ole 49 (L-168,049), a potent (Kb = 25 nM), selective
      antagonist of glucagon.

PMID- 10201822
TI  - Structure-activity relationship of a series of diaminoalkyl substituted
      benzimidazole as neuropeptide Y Y1 receptor antagonists.
AB  - A series of benzimidazoles (4) was synthesized and evaluated in vitro as potent
      and selective NPY Y1 receptor antagonists. Substitution of the piperidine
      nitrogen of 4 with appropriate R groups resulted in compounds with more than 80
      fold higher affinity at the Y receptor compared to the parent compound 5 (R = H).
      The most potent benzimidazole in this series was 21 (Ki = 0.052 nM).

PMID- 10201823
TI  - Synthesis of bisquinolines and their in vitro ability to produce methemoglobin in
      canine hemolysate.
AB  - Synthesis of a number of derivatives of bisquinolines (3-9) have been reported
      here. Effect of these compounds on in vitro methemoglobin formation and
      methemoglobin reductase activity has resulted in the identification of two
      potential compounds (5 & 7), showing negligible methemoglobin toxicity.

PMID- 10201824
TI  - Synthesis of glucuronides of multidrug resistance reversing drug MS-209.
AB  - We synthesized the glucuronides of MS-209 to identify the two main unknown
      metabolites in human urine. Reaction of MS-209 and glucuronyl
      trichloroacetimidate gave two beta-isomers, which were each glucuronate of (R)-
      and (S)-MS-209. These spectrum data were identical with the metabolites.

PMID- 10201825
TI  - Solid-phase synthesis of benzisothiazolones as serine protease inhibitors.
AB  - An efficient solid-phase synthesis of benzisothiazolone-1,1-dioxide-based serine
      protease inhibitors involving alkylation of carboxylic acids with N
      (bromomethyl)benzisothiazolone-1,1-dioxide has been developed. An example using
      this procedure for preparation of a library of human mast cell tryptase
      inhibitors is described.

PMID- 10201826
TI  - Synthesis of oxytocin antagonists containing conformationally constrained amino
      acids in position 2.
AB  - Analogues of oxytocin containing D-Trp, 2-amino-1,2,3,4-tetrahydronaphthalene-1
      carboxylic acid (Atc) or 1,2,3,4-tetrahydro-beta-carboline-1-carboxylic acid
      (Car) with R or S configurations in position 2 were synthetized, and their
      receptor bindings were tested on isolated guinea-pig uterus, rat liver and rat
      kidney inner medulla plasma membranes. The peptides were synthetized in the solid
      phase by using racemates of Car and Atc. The resulting diastereomeric mixtures
      were separated by means of RP-HPLC. The binding to the oxytocin receptor was
      somewhat decreased for the Atc isomers and dramatically decreased for both R- and
      S-Car, while the D-Trp-containing analogue displayed a relatively high receptor
      affinity. However, the V1 receptor affinities were almost the same as those of
      the parent peptide for the Car-containing analogues and dramatically decreased
      for the S-Atc substituted analogue, which has a relatively high OT/V1 receptor
      selectivity of 44.5.

PMID- 10201827
TI  - Synthesis and activity of 2-(sulfonamido)methyl-carbapenems: discovery of a
      novel, anti-MRSA 1,8-naphthosultam pharmacophore.
AB  - A series of 1beta-methyl carbapenems substituted at the 2-position with
      lipophilic, acyclic and cyclic (sulfonamido)methyl groups was prepared and
      evaluated for activity against resistant gram-positive bacteria. From these
      studies, the 1,8-naphthosultamyl group emerged as a novel, PBP2a-binding, anti
      MRSA pharmacophore worthy of further exploration.

PMID- 10201829
TI  - 1-Aminoisoquinoline as benzamidine isoster in the design and synthesis of orally
      active thrombin inhibitors.
AB  - Replacement of the highly basic benzamidine moiety of NAPAP by the moderately
      basic 1-aminoisoquinoline moiety resulted in thrombin inhibitors with improved
      selectivity towards trypsin and enhanced Caco-2 cell permeability.

PMID- 10201828
TI  - Synthesis and properties of 2-(naphthosultamyl)methyl-carbapenems with potent
      anti-MRSA activity: discovery of L-786,392.
AB  - A series of 1beta-methyl-2-(naphthosultamyl)methyl-carbapenems bearing dicationic
      groups on the naphthosultamyl moiety was prepared and evaluated for activity
      against resistant gram-positive bacteria. Based on a combination of excellent in
      vitro antibacterial activity, acceptable mouse acute toxicity, and a desirable
      fragmentation pattern on beta-lactam ring opening, the analog 2g (L-786,392) was
      selected for extended evaluation.

PMID- 10201830
TI  - First hydroxamate inhibitors for carboxypeptidase A. N-acyl-N-hydroxy-beta
      phenylalanines.
AB  - A series of N-acyl-N-hydroxy-beta-Phe were designed, synthesized, and shown to
      have potent inhibitory activity for carboxypeptidase A (CPA). They are the first
      examples of CPA inhibitors having a hydroxamate functionality.

PMID- 10201831
TI  - Effects of 3alpha- and 3beta-galactosylated alpha-galactosylceramides on the
      immune system.
AB  - We compared effects of alpha-galactosylceramide (alpha-GalCer) and its 3alpha- or
      3beta-galactosylated derivatives on the proliferation of murine spleen cells. The
      3alpha-galactosylated alpha-GalCer showed stronger proliferative response than
      the parental alpha-GalCer, but the 3beta-galactosylated alpha-GalCer possessed
      weaker activity than the alpha-GalCer. In addition, alpha-Gal-3-Cer did not show
      immunostimulatory activity.

PMID- 10201832
TI  - Potent inhibitors of protein farnesyltransferase: heteroarenes as cysteine
      replacements.
AB  - Synthesis and biological evaluation of heteroarenes as reduced cysteine
      replacements are described. Of the heteroaryl groups examined with respect to FT
      inhibitor FTI-276 (1), pyridyl was the replacement found to be most effective.
      Substitutions at C4 of the pyridyl moiety did not affect the in vitro activity.
      Compound 9a was found to have moderate in vivo bioavailability.

PMID- 10201833
TI  - Lipase-catalyzed acetylation of N-acetylneuraminic acid derivative.
AB  - A facile preparation of triacetylated derivative of 2-phenylthioglycoside of N
      acetylneuraminic acid (4) was achieved by treatment with lipase PS in vinyl
      acetate. The major product 4 has a free hydroxyl group at C-7. Results of time
      course HPLC analysis indicate that the reactivity of the hydroxyl groups under
      this condition is in the following order; C-9 > C-4 > C-8 > C-7.

PMID- 10201834
TI  - Antitumor agents 187: synthesis and cytotoxicity of substituted 8,8-dimethyl
      2H,8H-pyrano[6,5-h]quinoline-2-one and related compounds.
AB  - Several substituted 8,8-dimethyl-2H,8H-pyrano[6,5-h]quinoline-2-ones and related
      compounds were synthesized and evaluated for their in vitro cytotoxicity against
      a panel of human tumor cell lines. The most active compound (3) showed
      significant cytotoxic activity with GI50 values in the micromolar range.

PMID- 10201835
TI  - The solution structures of calyculin A and dephosphonocalyculin A by NMR.
AB  - The NMR solution structure of calyculin A (1) in chloroform exhibits
      intramolecular interactions, resembling the original crystal structure. In
      methanol, calyculin A has the hydrogen bonding moieties solvent exposed.
      Dephosphonocalyculin A in chloroform resembles calyculin A in chloroform and the
      crystal structure of calyculin A. Dephosphonocalyculin A in methanol resembles
      calyculin A in methanol.

PMID- 10201836
TI  - Simple one-pot synthesis of a 2'-tritium labeled C-deoxynucleoside.
AB  - The deoxygenation and 2'-labeling of a C-ribonucleoside by reductive elimination
      with tri-n-butyltin hydride[3H] in a one-pot reaction is described. The approach
      is a safe, simple, efficient, and general method for 2'-labeling of nucleosides.

PMID- 10201837
TI  - Octa- and nonaprenylhydroquinone sulfates, inhibitors of alpha1,3
      fucosyltransferase VII, from an Australian marine sponge Sarcotragus sp.
AB  - Alpha1,3-fucosyltransferase (Fuc TVII) is a key enzyme in the biosynthesis of
      selectin ligands. We have isolated two inhibitors of Fuc TVII from a marine
      sponge Sarcotragus sp. They were characterized as octa- and
      nonaprenylhydroquinone sulfates on the basis of spectral data. These compounds
      inhibited Fuc-TVII with IC50 values of 3.9 and 2.4 microg/mL, respectively.

PMID- 10201838
TI  - Antimalarial activity of 3-hydroxyalkyl-2-methylene-propionic acid derivatives.
AB  - Several Baylis-Hillman adducts and their derivatives were synthesized and
      evaluated as targeted potential anti-malarials. The compounds 4, 7 and 9 were
      found to have highest potency against P. falciparum in vitro. The in vivo test
      result of compound 4 and 9 against P. berghei demonstrated activity at 80 mg/Kg
      dose level.

PMID- 10201839
TI  - Studies towards the identification of potent, selective and bioavailable thrombin
      inhibitors.
AB  - The application of selection criteria, based on potency and physicochemical
      parameters, to a candidate library of thrombin inhibitors is described. The
      utility of the approach is exemplified by the discovery of a potent, selective
      and bioavailable thrombin inhibitor 62.

PMID- 10201840
TI  - A new class of potent RAR antagonists: dihydroanthracenyl, benzochromenyl and
      benzothiochromenyl retinoids.
AB  - The synthesis and biological activity of a novel series of tricyclic retinoic
      acid receptor antagonists are described. These compounds bind with high affinity
      to the RARs and are potent antagonists of retinoid function in in vitro and in
      vivo systems.

PMID- 10201842
TI  - Human beta3 adrenergic receptor agonists containing imidazolidinone and
      imidazolone benzenesulfonamides.
AB  - The cyclopentylpropylimidazolidinone L-766,892 is a potent beta3 AR agonist (EC50
      5.7 nM, 64% activation) with 420- and 130-fold selectivity over binding to the
      beta1 and beta2 ARs, respectively. In anesthetized rhesus monkeys, L-766,892
      elicited dose-dependent hyperglycerolemia (ED50 0.1 mg/kg) with minimal effects
      on heart rate.

PMID- 10201841
TI  - Human beta3 adrenergic receptor agonists containing cyclic
      ureidobenzenesulfonamides.
AB  - Human beta3 adrenergic receptor agonists containing 5-membered ring ureas were
      shown to be potent partial agonists with excellent selectivity over beta1 and
      beta2 binding. L-760,087 (4a) and L-764,646 (5a) (beta3 EC50 = 18 and 14 nM,
      respectively) stimulate lipolysis in rhesus monkeys (ED50 = 0.2 and 0.1 mg/kg,
      respectively) with minimal effects on heart rate. Oral absorption in dogs is
      improved over other urea analogs.

PMID- 10201843
TI  - Dibasic benzo[B]thiophene derivatives as a novel class of active site directed
      thrombin inhibitors: 4. SAR studies on the conformationally restricted C3-side
      chain of hydroxybenzo[B]thiophenes.
AB  - A novel series of benzo[b]thiophene diamine thrombin inhibitors with a
      conformationally restricted C3-side chain 3 was investigated. The constrained C3
      side chain by a cyclohexyl ring contributed to not only an additive but also a
      synergistic effect on the thrombin inhibitory activity. The SAR studies resulted
      in the discovery of a potent thrombin inhibitor 27 that was over 750-fold more
      potent than the initial lead compound 1.

PMID- 10201844
TI  - Synthesis and biological activity of oxo-7H-benzo[e]perimidine-4-carboxylic acid
      derivatives as potent, nonpeptide corticotropin releasing factor (CRF) receptor
      antagonists.
AB  - A novel series of derivatives of oxo-7H-benzo[e]perimidine-4-carboxylic acid (I)
      potently displaced radioligand binding of 125I-CRF to both CRF1 and CRF2
      receptors. The members of this series antagonized CRF-stimulated cAMP formation
      and CRF-stimulated corticotropin release from rat pituitary in vivo. These are
      the first nonpeptide antagonists to show activity at both CRF1 and CRF2
      receptors.

PMID- 10201845
TI  - Efficient synthesis of 3-aminodigoxigenin and 3-aminodigitoxigenin probes.
AB  - Oxidation of digoxigenin and digitoxigenin to the 3-ketones followed by reductive
      amination produced a mixture of amine epimers. The inability to separate the
      epimeric mixtures of chemiluminescent digoxigenin probes derived by conjugation
      to the acridinium label prompted us to develop an HPLC method to separate the
      amines. Labeling of the pure amines resulted in good yields of the isomerically
      pure probes.

PMID- 10201846
TI  - Dibasic benzo[b]thiophene derivatives as a novel class of active site directed
      thrombin inhibitors: 2. Sidechain optimization and demonstration of in vivo
      efficacy.
AB  - Potent, subnanomolar thrombin inhibitors 4, 5, and 6 are developed through side
      chain optimization of novel, benzo[b]thiophene-based small organic entities 2 and
      3 and through SAR additivity studies of the new structural elements identified. X
      ray crystallographic studies of 4b-thrombin complex revealed a hydrophobic and an
      electrostatic interaction of these new elements with thrombin at the S2 and S3
      binding sites. In vitro and in vivo pharmacological studies showed that 4, 5, and
      6 are potent anticoagulants in human plasma with demonstrated antithrombotic
      efficacy in a rat model of thrombosis.

PMID- 10201847
TI  - Synthesis and electrochemical study of a new chiral tris-catecholamide analogue
      of enterobactin.
AB  - The comparison of siderophore complex redox potentials with those of
      physiological reductants may aid in the clarification of the mechanism of iron
      metabolism. In this paper, a new chiral tris-catecholamide compound N,N',N''-tris
      (2,3-dihydroxybenzoyl)-1,1,1-tris-(L-methioninemethyl++ +)-ethane or H6L (11) has
      been synthesised in nine steps, and may mimic the release of iron from
      enterobactin to the agents which are directly involved in cell metabolism. The
      choice of methionine as a constituent of the siderophore incorporates divalent
      sulphur which leads to the increase of the reduction potential of the
      siderophore, and consequently facilitates the iron release [Fe(III)/Fe(II) redox
      potential E(1/2)=-0.749 V vs (SCE)].

PMID- 10201848
TI  - Synthesis of 2'-C-alpha-difluoromethylarauridine and its 3'-O-phosphoramidite
      incorporation into a hammerhead ribozyme.
AB  - The 2'-C-difluoromethylated nucleoside 4 was synthesized starting from uridine. 4
      was then converted to the 3'-O-phosphoramidite derivative 5 and was incorporated
      into a hammerhead ribozyme (7). The cleavage characteristics of the modified
      oligonucleotide have been analysed.

PMID- 10201849
TI  - Synthesis of alpha-C(1-->3)-mannopyranoside of N-acetylgalactosamine, a new beta
      galactosidase inhibitor.
AB  - Radical C-glycosidation of a 3-methylidene-7-oxabicyclo[2.2.1]heptan-2-one
      derivative with acetobromomannose gave a alpha-C-mannopyranoside that was
      converted into alpha-D-ManpCH2(1-->3)-D-GalNAc, a C-disaccharide that inhibits
      beta-galactosidase from jack bean with IC50 = 9.4 microM and Ki = 7.5 microM
      (mixed mode of inhibition).

PMID- 10201850
TI  - The effects of group size and group economic factors on collaboration: a study of
      the financial performance of rural hospitals in consortia.
AB  - STUDY QUESTIONS: To determine factors that distinguish effective rural hospital
      consortia from ineffective ones in terms of their ability to improve members'
      financial performance. Two questions in particular were addressed: (1) Do large
      consortia have a greater collective impact on their members? (2) Does a
      consortium's economic environment determine the degree of collective impact on
      members? DATA SOURCES AND STUDY SETTING: Based on the hospital survey conducted
      during February 1992 by the Robert Wood Johnson Hospital-Based Rural Health Care
      project of rural hospital consortia. The survey data were augmented with data
      from Medicare Cost Reports (1985-1991), AHA Annual Surveys (1985-1991), and other
      secondary data. STUDY DESIGN: Dependent variables were total operating profit,
      cost per adjusted admission, and revenue per adjusted admission. Control
      variables included degree of group formalization, degree of inequality of
      resources among members (group asymmetry), affiliation with other consortium
      group(s), individual economic environment, common hospital characteristics (bed
      size, ownership type, system affiliation, case mix, etc.), year (1985-1991), and
      census region dummies. PRINCIPAL FINDINGS: All dependent variables have a
      curvilinear association with group size. The optimum group size is somewhere in
      the neighborhood of 45. This reveals the benefits of collective action (i.e.,
      scale economies and/or synergy effects) and the issue of complexity as group size
      increases. Across analyses, no strong evidence exists of group economic
      environment impacts, and the environmental influences come mainly from the local
      economy rather than from the group economy. CONCLUSION: There may be some success
      stories of collaboration among hospitals in consortia, and consortium effects
      vary across different collaborations. RELEVANCE/IMPACT: When studying consortia,
      it makes sense to develop a typology of groups based on some performance
      indicators. The results of this study imply that government, rural communities,
      and consortium staff and steering committees should forge the consortium concept
      by expanding membership in order to gain greater financial benefits for
      individual hospitals.

PMID- 10201851
TI  - The adoption of provider-based rural health clinics by rural hospitals: a study
      of market and institutional forces.
AB  - OBJECTIVE: To examine the response of rural hospitals to various market and
      organizational signals by determining the factors that influence whether or not
      they establish a provider-based rural health clinic (RHC) (a joint
      Medicare/Medicaid program). DATA SOURCES/STUDY SETTING: Several secondary sources
      for 1989-1995: the AHA Annual Survey, the PPS Minimum Data Set and a list of RHCs
      from HCFA, the Area Resource File, and professional associations. The analysis
      includes all general medical/surgical rural hospitals operating in the United
      States during the study period. STUDY DESIGN: A longitudinal design and pooled
      cross-sectional data were used, with the rural hospital as the unit of analysis.
      Key variables were examined as sets and include measures of competitive pressures
      (e.g., hospital market share), physician resources, nurse practitioner/physician
      assistant (NP/PA) practice regulation, hospital performance pressures (e.g.,
      operating margin), innovativeness, and institutional pressure (i.e., the
      cumulative force of adoption). PRINCIPAL FINDINGS: Adoption of provider-based
      RHCs by rural hospitals appears to be motivated less as an adaptive response to
      observable economic or internal organizational signals than as a reaction to
      bandwagon pressures. CONCLUSIONS: Rural hospitals with limited resources may
      resort to imitating others because of uncertainty or a limited ability to fully
      evaluate strategic activities. This can result in actions or behaviors that are
      not consistent with policy objectives and the perceived need for policy changes.
      Such activity in turn could have a negative effect on some providers and some
      rural residents.

PMID- 10201852
TI  - Financial and organizational determinants of hospital diversification into
      subacute care.
AB  - OBJECTIVE: To examine the financial, market, and organizational determinants of
      hospital diversification into subacute inpatient care by acute care hospitals in
      order to guide hospital managers in undertaking such diversification efforts.
      STUDY SETTING: All nongovernment, general, acute care, community hospitals that
      were operating during the years 1985 through 1991 (3,986 hospitals in total).
      DATA SOURCES: Cross-sectional, time-series data were drawn from the American
      Hospital Association's (AHA) Annual Survey of Hospitals, the Health Care
      Financing Administration's (HCFA) Medicare Cost Reports, a latitude and longitude
      listing for all community hospital addresses, and the Area Resource File (ARF)
      published in 1992, which provides county level environmental variables. STUDY
      DESIGN: The study is longitudinal, enabling the specification of temporal
      patterns in conversion, causal inferences, and the treatment of right-censoring
      problems. The unit of analysis is the individual hospital. KEY FINDINGS:
      Significant differences were found in the average level of subacute care offered
      by investor-owned versus tax-exempt hospitals. After controlling for selection
      bias, financial performance, risk, size, occupancy, and other variables, IO
      hospitals offered 31.3 percent less subacute care than did NFP hospitals.
      Financial performance and risk are predictors of IO hospitals' diversification
      into subacute care, but not of NFP hospitals' activities in this market. Resource
      availability appears to expedite expansion into subacute care for both types of
      hospitals. CONCLUSIONS: Investment criteria and strategy differ between investor
      owned and tax-exempt hospitals.

PMID- 10201853
TI  - Analysis of the rationale for, and consequences of, nonprofit and for-profit
      ownership conversions.
AB  - OBJECTIVES: To examine percursors to private hospitals conversion, both from
      nonprofit status to for-profit status and from for-profit to nonprofit status, as
      well as the effect of hospital conversions on hospital profitability, efficiency,
      staffing, and the probability of closure. DATA SOURCES: The Health Care Financing
      Administration's Medicare Cost Reports and the American Hospital Association's
      Annual Survey of Hospitals. STUDY DESIGN: Bivariate and multivariate analyses
      comparing conversion hospitals to nonconversion hospitals over time were
      conducted. DATA EXTRACTION METHODS: The study sample consisted of all private
      acute care hospital conversions that occurred from 1989 through 1992. PRINCIPAL
      FINDINGS: Hospitals that converted had significantly lower profit margins prior
      to converting than did nonconversion hospitals. This was particularly true for
      nonprofit to for-profit conversions. After converting, both nonprofit and for
      profit hospitals significantly improved their profitability. Nonprofit to for
      profit hospital conversions were associated with a decrease in the ratio of staff
      to patients. No association was found between for-profit to nonprofit conversion
      and staff-to-patient ratios. The difference seems partially attributed to the
      fact that nonprofit hospitals that converted had higher staff ratios than the
      industry average. For-profit to nonprofit hospital conversions were associated
      with an increase in the ratio of registered nurses to patients and administrators
      to patients, despite the fact that nonprofit and for-profit hospitals did not
      differ in these ratios. CONCLUSIONS: The improvement in financial performance
      following hospital conversions may be a benefit to the community that
      policymakers want to consider when regulating hospital conversions.

PMID- 10201854
TI  - Evaluating the sale of a nonprofit health system to a for-profit hospital
      management company: the Legacy Experience.
AB  - OBJECTIVE: To introduce and develop a decision model that can be used by the
      leadership of nonprofit healthcare organizations to assist them in evaluating
      whether selling to a for-profit organization is in their community's best
      interest. STUDY SETTING/DATA SOURCES: A case study of the planning process and
      decision model that Legacy Health System used to evaluate whether to sell to a
      for-profit hospital management company and use the proceeds of the sale to
      establish a community health foundation. Data sources included financial
      statements of benchmark organizations, internal company records, and numerous
      existing studies. STUDY DESIGN: The development of the multivariate model was
      based on insight gathered through a review of the current literature regarding
      the conversion of nonprofit healthcare organizations. DATA COLLECTION/EXTRACTION
      METHODS: The effect that conversion from nonprofit to for-profit status would
      have on each variable was estimated based on assumptions drawn from the current
      literature and on an analysis of Legacy and for-profit hospital company data.
      PRINCIPAL FINDINGS: The results of the decision model calculations indicate that
      the sale of Legacy to a for-profit firm and the subsequent creation of a
      community foundation would have a negative effect on the local community.
      CONCLUSIONS: The use of the decision model enabled senior management and trustees
      to systematically address the conversion question and to conclude that continuing
      to operate as a nonprofit organization would provide the most benefit to the
      local community. The model will prove useful to organizations that decide to sell
      to a for-profit organization as well as those that choose to continue nonprofit
      operations. For those that decide to sell, the model will assist in minimizing
      any potential negative effect that conversion may have on the community. The
      model will help those who choose not to sell to develop a better understanding of
      the organization's value to the community.

PMID- 10201855
TI  - Access and use of medications in HIV disease.
AB  - OBJECTIVE: To examine if measures of access to medical care are associated with
      outpatient use of antiretroviral and Pneumocystis carinii pneumonia (PCP)
      medications among a cohort of individuals with HIV disease. DATA SOURCES: Adults
      who participated in a series of up to six interviews as part of the AIDS Costs
      and Services Utilization Survey (ACSUS). ACSUS, a panel survey of persons with
      HIV disease, was undertaken from 1991 through 1992. STUDY DESIGN: The Andersen
      Behavioral Model of Health Services Use provided the conceptual framework for the
      study. Logistic regression analyses with generalized estimating equations were
      conducted to determine the effects of predisposing, enabling, and need-for-care
      factors on the odds of antiretroviral or PCP medication use. The analytic sample
      consisted of 1,586 respondents whose 7,652 interviews provided the data.
      PRINCIPAL FINDINGS: The multivariate analysis showed that being female (OR =
      0.76; 95% C.I. = 0.60-0.95), ages 15 to 24 years (OR = 0.64; 95% C.I. = 0.44
      0.92), and having a hospitalization (OR = 0.73; 95% C.I. = 0.63-0.84) were
      associated with lower odds of using antiretrovirals. African American race (OR =
      1.30; 95% C.I. = 1.04-1.62), having both public and private insurance (OR = 2.11;
      95% C.I. = 1.47-3.03), attending counseling (OR = 1.17; 95% C.I. = 1.02-1.34),
      having a usual source of care (OR = 1.70; 95% C.I. = 1.38-2.11), and clinical
      trials participation (OR = 1.52; 95% C.I. = 1.23-1.87) were associated with a
      higher odds of use. Similar results were obtained for analyses of PCP medication
      use. CONCLUSIONS: Sociodemographic differences exist in access and use of
      prescription drugs within the ACSUS cohort. The results suggest that women and
      those ages 15 to 24 years have poor access to some medications that improve
      survival in HIV disease.

PMID- 10201856
TI  - The role of medical problems and behavioral risks in explaining patterns of
      prenatal care use among high-risk women.
AB  - OBJECTIVE: To examine the associations between maternal medical conditions and
      behavioral risks and the patterns of prenatal care use among high-risk women.
      DATA SOURCE/STUDY DESIGN: Data on over 25,000 high-risk deliveries to African
      American and white women using multinomial logistic regression to predict the
      odds of adequate-plus care relative to three other categories of care. DATA
      COLLECTION/EXTRACTION METHODS: Data were extracted from records maintained by the
      University of Florida/Shands Hospital maternity clinic on all deliveries between
      1987 and 1994; records for white and for African American women were subset to
      examine racial differences in medical conditions, health behaviors, and patterns
      of prenatal care use. PRINCIPAL FINDINGS: Net of sociodemographic and fertility
      related characteristics, African American and white women with late antepartum
      conditions and hypertension problems had significantly higher odds of receiving
      adequate-plus care, as well as no care or inadequate care, relative to adequate
      care. White women with gynecological disease and medical/surgical problems were
      significantly less likely to receive no care or inadequate care, as were African
      American women with gynecological disease. CONCLUSIONS: Maternal medical
      conditions explain much but not all of the adequate-plus prenatal care use. More
      than 13 percent of African American women and 20 percent of white women with no
      reported medical problems or behavioral risks used adequate-plus care. Additional
      research is needed to understand this excess use and its possibilities in
      mediating birth outcomes.

PMID- 10201857
TI  - Risk-adjusted outcome models for public mental health outpatient programs.
AB  - OBJECTIVE: To develop and test risk-adjustment outcome models in publicly funded
      mental health outpatient settings. We developed prospective risk models that used
      demographic and diagnostic variables; client-reported functioning, satisfaction,
      and quality of life; and case manager clinical ratings to predict subsequent
      client functional status, health-related quality of life, and satisfaction with
      services. DATA SOURCES/STUDY SETTING: Data collected from 289 adult clients at
      five- and ten-month intervals, from six community mental health agencies in
      Washington state located primarily in suburban and rural areas. Data sources
      included client self-report, case manager ratings, and management information
      system data. STUDY DESIGN: Model specifications were tested using prospective
      linear regression analyses. Models were validated in a separate sample and
      comparative agency performance examined. PRINCIPAL FINDINGS: Presence of severe
      diagnoses, substance abuse, client age, and baseline functional status and
      quality of life were predictive of mental health outcomes. Unadjusted versus risk
      adjusted scores resulted in differently ranked agency performance. CONCLUSIONS:
      Risk-adjusted functional status and patient satisfaction outcome models can be
      developed for public mental health outpatient programs. Research is needed to
      improve the predictive accuracy of the outcome models developed in this study,
      and to develop techniques for use in applied settings. The finding that risk
      adjustment changes comparative agency performance has important consequences for
      quality monitoring and improvement. Issues in public mental health risk
      adjustment are discussed, including static versus dynamic risk models,
      utilization versus outcome models, choice and timing of measures, and access and
      quality improvement incentives.

PMID- 10201858
TI  - Radionuclide radiology.

PMID- 10201859
TI  - Towards quality assurance of postgraduate training in radiology.

PMID- 10201860
TI  - Congenital bronchial atresia--presentation of three cases and a pictorial review.
AB  - Congenital bronchial atresia (CBA) is a rare anomaly that results from a
      congenital focal obliteration of a proximal segmental or subsegmental bronchus
      with the normal development of distal structures. The short atretic segment leads
      to accumulation of mucus within the distal bronchi to form a bronchocoele and
      underventilation of the affected part of the lung. The clinical and radiographic
      features of three cases of CBA are reported and the literature is reviewed.
      Radiologically, CBA is characterized by the presence of a branching opacity, the
      bronchocoele, radiating from the hilum surrounded by an area of hyperlucency.
      These features can be recognized on the chest radiograph but are more clearly
      defined by computed tomography. Fibreoptic bronchoscopy (FOB) is often required
      to exclude acquired proximal bronchial obstruction by tumour, foreign body or
      inflammatory stricture. In CBA a blind-ending bronchus may be revealed, although
      FOB is often normal. Bronchographic examination is generally abnormal but the
      appearances may be confusing and is rarely performed. Pathologically, CBA is
      characterized by a blind-ending bronchus associated with dilated distal bronchi
      containing impacted mucus. The surrounding lung parenchyma is hyperinflated due
      to collateral air drift. CBA can be identified accurately by imaging techniques
      which may make surgery unnecessary in asymptomatic cases.

PMID- 10201861
TI  - The value of specialist oncological radiology review of cross-sectional imaging.
AB  - AIM: To determine whether specialist oncological radiology review of outside
      cross-sectional imaging affects patient management. MATERIALS AND METHODS: Five
      hundred and twenty-six patients attending a regional oncology centre had review
      of outside cross-sectional imaging over a 1-year period. The number of
      examinations per patient, time interval between examination and review request,
      and examination technical adequacy were recorded in each case. More detailed
      evaluation of 124 patients included comparison of outside and review reports for
      major differences in interpretation by a medical oncologist who also evaluated
      the effect of the review on patient management. Examinations resulting in major
      report discrepancies were subjected to independent radiological adjudication.
      RESULTS: Eighty-one percent of examinations were reviewed within 3 months of
      being performed and 94% were considered technically adequate. The hard copy
      images provided were incomplete in 33% of cases and a calibration rule was absent
      in 9%. There was a major difference in interpretation in 34% of examinations, the
      most common cause being differences in interpretation of lymphadenopathy (52%),
      particularly in the mediastinum (19%). Other problems identified were the failure
      to record disease dimensions and absence of specific information on key organs in
      the outside reports. Specialist radiology review changed radiological staging in
      19% of patients, affected management in 7% of patients and resulted in a change
      in treatment in 4%. There was no correlation between management change and any
      particular tumour type. In 27% of cases, treatment decisions had been made before
      the review was requested. CONCLUSION: Specialist oncological radiology review of
      outside cross-sectional imaging changed radiological staging in 19% of cases but
      had little impact on patient management. Oncological cross-sectional imaging
      techniques in the North West of England are of high quality, probably helped by
      recent RCR guidelines.

PMID- 10201862
TI  - Grayscale and pulsed Doppler characteristics of non-cirrhotic portal fibrosis: a
      preliminary report.
AB  - AIM: Non-cirrhotic portal fibrosis is a common cause of portal hypertension in
      India. Inspite of this there is no published data delineating the imaging
      findings in patients with this disease. The aim of this study was to evaluate
      Grayscale and pulsed Doppler findings of the portal venous system in non
      cirrhotic portal fibrosis. MATERIALS AND METHODS: Grayscale and Doppler
      sonography was performed on 19 patients with clinically and histologically proven
      non-cirrhotic portal fibrosis. Portal venous flow was determined along with the
      portal venous diameter, congestive index of the portal vein, and the splenic
      index. Twenty normal control subjects were also studied. RESULTS: Doppler
      analysis revealed features of portal hypertension. These included increased
      portal venous flow, and congestive index (1062.1 +/- 199.7 vs 724.4 +/- 181.2;
      and 0.140 +/- 0.070 vs 0.049 +/- 0.011 respectively) when compared with the
      control group. Increased splenic index and dilatation of the portal venous
      diameter was also present (116.4 +/- 29.8 vs 45.8 +/- 7.0; and 14.3 +/- 1.5 vs
      10.3 +/- 1.1 respectively). Grayscale findings demonstrated echogenic and
      thickened intrahepatic portal venous branches in 10 cases. Subcapsular atrophy of
      the liver was seen in three cases. Varices were identified in 15 cases.
      CONCLUSION: Patients with non-cirrhotic portal fibrosis have features of portal
      hypertension at the time of presentation. Ultrasonic findings that include
      echogenic, thickened portal venous tracts and subcapsular liver atrophy were
      frequently observed in such cases and were not seen in the control group.

PMID- 10201863
TI  - A new magnesium-containing PEG-electrolyte solution for the oral lavage of the
      colon.
AB  - AIM: The aim of the present study was to verify whether the addition of magnesium
      ions to an electrolyte solution containing polyethylene glycol (PEG-ELS) for the
      oral lavage of the colon increases barium mucosal coating at the time of double
      contrast barium enema (DCBE) examination. MATERIALS AND METHODS: The two patients
      from 60 pairs of patients undergoing DCBE with a standardized technique were
      randomly subjected to bowel preparation with sennosides and an isotonic PEG-ELS
      (SELG, Promefarm, Italy), or sennosides and a modified isotonic SELG preparation
      to which 7.5 g/l of magnesium sulphate were added. Mucosal coating, residual
      fluid and colon cleansing were assessed independently by three radiologists. The
      null hypothesis was tested by means of Wilcoxon's signed-rank test. RESULTS:
      Barium mucosal coating was judged to be significantly better in the SELG-Mg
      members (P<0.0001). The amount of residual fluid was significantly lower in SELG
      Mg members (P<0.0001). There was no difference in colon cleansing (P = 0.690).
      These results demonstrate, in a simple way, that magnesium ions increase barium
      coating of the colon mucosa in vivo. The underlying mechanism seems to be the
      increase in viscosity of barium suspension by free water subtraction owing to the
      hydrophilia of magnesium ions. CONCLUSION: The integration of magnesium in a
      newly designed isotonic PEG-ELS could be the correcting factor for the poor
      barium mucosal coating that normal solutions for the oral colon lavage induce.

PMID- 10201864
TI  - Use of pelvic surface coil MR imaging for assessment of clinically localized
      prostate cancer with histopathological correlation.
AB  - We evaluated the ability of magnetic resonance imaging (MRI) operating at 1.0
      Tesla with a Helmholz pelvic surface coil to predict the pathological stage of
      prostate carcinoma. Radiological diagnosis was based on fast spin-echo axial T2
      weighted images with and without frequency selective fat-suppression and fast
      spin-echo coronal T2-weighted images. Thirty-one consecutive patients (mean age
      61 years, range 49 to 71 years) underwent pelvic MRI before radical
      prostatectomy. Correlation with whole-mount step-sections of the surgical
      specimens showed that the tumours were correctly localized in all but one
      prostate gland in which the tumour could not be seen on pelvic MRI. The
      transverse diameter of the visible tumour at pelvic MRI appeared to represent an
      approximate estimate of the true tumour dimension. Based on histopathologic whole
      mount step-sections of the surgical specimens, 22 of 31 patients (71%) had
      tumours extending beyond the confines of the prostatic capsule. The specificity
      for MRI to predict capsular penetration and seminal vesicle invasion was
      relatively high (0.80 and 0.86, respectively). The sensitivity was acceptable for
      capsular penetration (0.62) but poor for seminal vesicle invasion (0.30).

PMID- 10201865
TI  - Common duct diameter as an independent predictor of choledocholithiasis: is it
      useful?
AB  - We have evaluated the value of ultrasonographic measurement of common duct
      diameter in isolation from other predictors of choledocholithiasis. A cohort of
      223 patients who did not have a history of jaundice or pancreatitis and had
      normal liver function tests underwent pre-operative ultrasound of the common
      hepatic duct and then had elective (open) cholecystectomy with operative
      cholangiography. One hundred and ninety-one (86%) of all patients had a normal (<
      or = 5 mm) common duct and of these only 12 (6%) had common duct calculi. Of the
      32 patients who had a common duct diameter greater than 5 mm on pre-operative
      ultrasonography, 12 (37.5%) patients had ductal calculi. A pre-operatively
      dilated duct on ultrasonography has a high chance of containing stones and should
      be considered as a strong indication for pre-operative bile duct imaging or
      operative cholangiography.

PMID- 10201866
TI  - The transrectal ultrasound and MRI appearances of granulomatous prostatitis and
      its differentiation from carcinoma.
AB  - AIMS AND METHODS: Granulomatous prostatitis is a benign inflammatory condition of
      the prostate which can be mistaken for prostatic carcinoma both clinically and on
      ultrasound, but is distinguishable histologically. The transrectal ultrasound
      (TRUS) and magnetic resonance imaging (MRI) appearances of 10 patients with
      histologically confirmed granulomatous prostatitis were evaluated to try and
      identify any correlation between the two techniques or any specific features on
      MRI to help distinguish it from carcinoma. Clinical findings and serum prostatic
      specific antigen (PSA) levels were also evaluated. RESULTS: In five patients,
      both TRUS and MRI were concordant, showing only changes of benign prostatic
      hypertrophy (three patients) or showing no abnormality (two patients). In a
      further three patients, both TRUS and MRI were abnormal, with appearances
      suggestive of carcinoma. One of these patients had tuberculous prostatitis and
      had a past history of tuberculosis. In the remaining two patients, there was a
      discrepancy between TRUS and MRI findings, carcinoma being suspected on TRUS in
      one with a normal MRI, and carcinoma suspected on MRI in the other with a normal
      TRUS. CONCLUSION: There is no pattern of clinical, biochemical, ultrasound or MRI
      findings that allows a specific diagnosis of granulomatous prostatitis to be
      made, or differentiation from prostatic carcinoma.

PMID- 10201867
TI  - Percutaneous vertebral biopsy through intact bone: a coaxial bone transgressing
      technique with 18 gauge needle.
AB  - Advancement of radiologic technologies allows the detection of vertebral lesions
      at an earlier stage, thereby increasing the proportion of vertebral lesions that
      are surrounded by intact bone when they are detected. While biopsy guns are
      effective in obtaining good-quality tissue samples of osteolytic bone lesions,
      lesions that are covered by intact bone are not accessible with a biopsy gun. For
      percutaneous biopsy of osteolytic vertebral lesions, an intact-bone transgressing
      technique is described in which a simple, inexpensive and small-calibre (18
      gauge) instrument is used to allow multiple passage of 20-gauge biopsy guns for
      effective tissue sampling. In this series consisting of metastatic and
      myeloproliferative lesions, the effectiveness and safety of this well-tolerated
      technique are demonstrated in thoracic and lumbar vertebrae.

PMID- 10201868
TI  - Giant sigmoid diverticulum: a report of three cases.
AB  - The imaging appearances of three patients with a giant sigmoid diverticulum are
      described. The prominent feature was a large gaseous lucency noted in the lower
      abdomen on plain radiographs. Computed tomography (CT) was undertaken in two
      cases and in these a large gas filled collection was identified containing a
      small quantity of fluid. In the third case the collection was aspirated, contrast
      medium injected and a communication with the large bowel demonstrated. The
      condition is uncommon and needs to be distinguished from sigmoid and caecal
      volvulus.

PMID- 10201869
TI  - Primary pulmonary Hodgkin's disease: CT findings in three patients.
AB  - The computed tomography (CT) findings in three patients with primary pulmonary
      Hodgkin's disease are reported. Two patients had unilateral upper lobe cavitated
      masses and one patient had bilateral lower lobe nodules.

PMID- 10201870
TI  - Spontaneous false aneurysm of the radial artery in neurofibromatosis.

PMID- 10201872
TI  - Afferent loop obstruction: CT appearances of an unusual cause of acute
      pancreatitis.

PMID- 10201871
TI  - Hydronephrosis: a rare late complication of barium enema.

PMID- 10201873
TI  - Atypical chest pain from a left ventricular false aneurysm.

PMID- 10201874
TI  - The beneficial effects of fire alarms on the quality of intravenous urograms.

PMID- 10201875
TI  - Giant aggressive osteoma of the frontal sinus.

PMID- 10201876
TI  - CT findings in gallstone ileus.

PMID- 10201878
TI  - Use of an IVC filter in the management of IVC thrombosis.

PMID- 10201877
TI  - Bowel preparation prior to double contrast barium enema examination--comparison
      of Picolax and Fleet phosphosoda.

PMID- 10201879
TI  - Historical evolution of angiotensin II receptor blockers: therapeutic advantages.

PMID- 10201880
TI  - Angiotensin II and long-term arterial pressure regulation: the overriding
      dominance of the kidney.
AB  - The renin-angiotensin system (RAS) is one of the body's most powerful regulators
      of arterial pressure and body fluid volumes. Although the acute effects of
      angiotensin II (AngII), the primary active component of the RAS, on arterial
      pressure are mediated primarily by peripheral vasoconstriction, its chronic BP
      effects are closely intertwined with volume homeostasis, particularly with
      intrarenal actions that influence pressure natriuresis. AngII shifts pressure
      natriuresis toward higher BP primarily by increasing tubular reabsorption rather
      than decreasing GFR. In fact, activation of the RAS can serve as an important
      means of preventing decreases in GFR during volume depletion or circulatory
      depression. However, with prolonged excess AngII formation, particularly in
      association with hypertension or overperfusion of the kidney, AngII can
      contribute to glomerular injury and a gradual loss of nephron function through
      its hemodynamic actions. The multiple effects of AngII to increase tubular
      reabsorption provide a powerful mechanism to protect against volume depletion and
      low BP. However, when AngII levels are inappropriately elevated, this
      necessitates increased arterial pressure to maintain sodium and water balance.
      Blockade of the RAS has proved to be a powerful therapeutic tool for lowering BP
      and improving kidney function in disorders such as hypertension, congestive heart
      failure, and chronic renal disease.

PMID- 10201881
TI  - Intrarenal angiotensin II generation and renal effects of AT1 receptor blockade.
AB  - The intrarenal renin-angiotensin system plays a critical role in the paracrine
      regulation of renal function and the pathophysiology of hypertension. Angiotensin
      II (AngII) is formed intrarenally from systemically delivered angiotensin I
      (AngI) and intrarenally formed AngI. Intrarenal AngII content, which is greater
      than can be explained by the circulating AngII concentrations, is
      compartmentalized such that proximal tubule concentrations of AngI and AngII
      greatly exceed plasma concentrations. Proximal tubule cells are thought to
      secrete AngII or precursors of AngII into the tubular fluid to activate luminal
      AngII receptors. Recent immunohistochemical studies have demonstrated an
      abundance of AT1 receptors on the luminal surface of proximal and distal tubule
      cells and on afferent and efferent arteriolar vascular smooth muscle cells and
      mesangial cells of glomeruli. Activation of luminal AT1 receptors stimulates
      tubular sodium reabsorption rate. To evaluate the direct effects of AT1 receptor
      blockade on renal function in AngII-dependent hypertension, experiments were
      performed on two-kidney, one-clip (2K1C) Goldblatt hypertensive rats. Although
      the nonclipped kidney is renin-depleted, the intrarenal AngII levels are not
      suppressed, and AngII concentrations in proximal tubular fluid remain high (10(
      8) M). Candesartan was administered into the renal artery of nonclipped kidneys
      to avoid the confounding consequences of decreases in arterial pressure. Blockade
      of intrarenal AT1 receptors elicited significant increases in GFR, renal blood
      flow, sodium excretion, and fractional sodium excretion, suggesting synergistic
      actions on tubular transport and vascular smooth muscle cells.

PMID- 10201882
TI  - Angiotensin receptor blockers: pharmacology and clinical significance.
AB  - Several imidazole derivatives that bind specifically to the angiotensin II type 1
      receptor (the angiotensin receptor blockers, or ARB), have been developed in
      recent years and made available to clinicians. Preclinical studies revealed some
      differences in pharmacokinetic parameters and in vitro effects. However, most of
      the reported physiologic effects associated with ARB administration are similar
      to those of angiotensin-converting enzyme inhibitors (ACEI). In short-term
      clinical studies, the efficacy of ARB in reducing BP (BP) was similar to that of
      the ACEI, whereas (with a few exceptions) the side-effect profile was comparable
      to that of placebo. Whether targeting antihypertensive treatment with such a high
      specificity within the renin cascade carries major clinical advantages over
      inhibiting angiotensin-converting enzyme remains to be demonstrated.

PMID- 10201883
TI  - Comparative antihypertensive effects of angiotensin II receptor antagonists.
AB  - Blockade of the renin-angiotensin system is recognized as an effective approach
      for the treatment of hypertension and congestive heart failure. It is possible to
      antagonize the effects of angiotensin II (AngII) by blocking its receptors, using
      nonpeptide receptor antagonists. Six angiotensin receptor blockers (ARB) have
      been approved for the treatment of hypertension: losartan, valsartan, irbesartan,
      candesartan, telmisartan, and eprosartan. These new drugs are highly selective
      for the AT1 receptor subtype and induce dose-dependent inhibition of the BP
      response to exogenous AngII. Numerous double-blind, placebo-controlled studies
      have demonstrated that ARB are efficacious for treating mild, moderate, and
      severe hypertension. When compared with other classes of antihypertensive agents,
      ARB are as effective as angiotensin-converting enzyme inhibitors, calcium
      antagonists, thiazide diuretics, and beta-blockers. One advantage of ARB as a
      class is their excellent tolerability and side effect profile. Several large
      clinical trials of ARB are now under way to demonstrate their benefits in
      hypertension, heart failure, and type II diabetic nephropathy.

PMID- 10201885
TI  - Another SANE program is up and running.

PMID- 10201884
TI  - Angiotensin receptor blockers in chronic renal disease: the promise of a bright
      clinical future.
AB  - Pharmacologic interruption of the renin-angiotensin system (RAS) with angiotensin
      converting enzyme inhibitors (ACEI) is considered a standard therapeutic
      intervention for patients with chronic renal disease, regardless of whether
      systemic hypertension is present. The advent of orally active angiotensin
      receptor blockers (ARB) increases the number of therapeutic options for
      inhibiting the RAS in patients with chronic renal diseases. Clinical studies of
      ARB that can be compared with large-scale ACEI clinical trials have yet to be
      completed. More than a dozen experimental studies comparing ARB with ACEI suggest
      that the two classes of drugs share similar renoprotective properties. Like ACEI,
      ARB are effective antihypertensive and antiproteinuric agents, which greatly
      reduce glomerular and tubulointerstitial scarring. Although both reduce
      stimulation of the AT1 receptor, ARB lack the kinin-potentiating effects of ACEI.
      ARB may exert antifibrotic actions via the AT2 receptor, through increased levels
      of angiotensin II resulting from AT1 receptor blockade. Despite these
      pharmacologic distinctions, recent studies have not detected differences in
      renoprotection between ARB and ACEI. In the context of RAS inhibition, the
      magnitude of antihypertensive and antiproteinuric effects achieved appears to be
      the major determinant of renoprotection, not the class of drug used. Thus,
      experimental data suggest that ARB will fulfill their promise as effective agents
      to be used as mainstays in multifaceted clinical strategies designed to slow or
      arrest the progression of chronic renal disease. Confirmation of this view awaits
      the results of clinical trials.

PMID- 10201887
TI  - Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to
      lipopolysaccharide: evidence for TLR4 as the Lps gene product.
AB  - The human homologue of Drosophila Toll (hToll), also called Toll-like receptor 4
      (TLR4), is a recently cloned receptor of the IL-1/Toll receptor family.
      Interestingly, the TLR4 gene has been localized to the same region to which the
      Lps locus (endotoxin unresponsive gene locus) is mapped. To examine the role of
      TLR4 in LPS responsiveness, we have generated mice lacking TLR4. Macrophages and
      B cells from TLR4-deficient mice did not respond to LPS. All these manifestations
      were quite similar to those of LPS-hyporesponsive C3H/HeJ mice. Furthermore,
      C3H/HeJ mice have, in the cytoplasmic portion of TLR4, a single point mutation of
      the amino acid that is highly conserved among the IL-1/Toll receptor family.
      Overexpression of wild-type TLR4 but not the mutant TLR4 from C3H/HeJ mice
      activated NF-kappaB. Taken together, the present study demonstrates that TLR4 is
      the gene product that regulates LPS response.

PMID- 10201888
TI  - Cutting edge: LFA-1 is required for liver NK1.1+TCR alpha beta+ cell development:
      evidence that liver NK1.1+TCR alpha beta+ cells originate from multiple pathways.
AB  - Using mice deficient for LFA-1, CD44, and ICAM-1, we examined the role of these
      adhesion molecules in NK1.1+TCR alpha beta+ (NKT) cell development. Although no
      defect in NKT cell development was observed in CD44-/- and ICAM-1-/- mice, a
      dramatic reduction of liver NKT cells was observed in LFA-1-/- mice. Normal
      numbers of NKT cells were present in other lymphoid organs in LFA-1-/- mice. When
      LFA-1-/- splenocytes were injected i.v. into wild-type mice, the frequency of NKT
      cells among donor-derived cells in the recipient liver was normal. In contrast,
      when LFA-1-/- bone marrow (BM) cells were injected i.v. into irradiated wild-type
      mice, the frequency of liver NKT cells was significantly lower than that of mice
      injected with wild-type BM cells. Collectively, these data indicate that LFA-1 is
      required for the development of liver NKT cells, rather than the migration to
      and/or subsequent establishment of mature NKT cells in the liver.

PMID- 10201889
TI  - Cutting edge: receptor-mediated endocytosis of heat shock proteins by
      professional antigen-presenting cells.
AB  - Immunization with heat shock proteins (HSPs) induces Ag-specific CTL responses.
      The specificity of the immune response is based on peptides associated with HSPs.
      To investigate how exogenous HSP/peptide complexes gain access to the MHC class I
      restricted Ag presentation pathway, we incubated the monocytic cell line P388D1
      and the dendritic cell line D2SC/1 with gold-labeled HSPs gp96 and HSC70. We show
      that HSPs bind specifically to the surface of these APCs and are internalized
      spontaneously by receptor-mediated endocytosis, demonstrating the existence of
      specific receptors for HSPs on these cells. In addition, we observe
      colocalization of internalized HSPs and surface MHC class I molecules in early
      and late endosomal structures. These findings provide possible explanations for
      the immunogenicity of HSP/peptide complexes and for the transfer of HSP
      associated peptides onto MHC class I molecules.

PMID- 10201890
TI  - Cutting edge: a test of the dominant negative signal model for TCR antagonism.
AB  - The mechanism by which TCR antagonists interfere with T cell activation is
      unclear. One popular hypothesis is that incomplete early signaling events induced
      by these ligands dominantly inhibit the T cell's ability to respond to a
      copresented agonist ligand. Here we test this "dominant negative" signal
      hypothesis by studying T cells expressing two distinct MHC class I-restricted
      TCRs (2C and OT-I). Although responses through each TCR can be efficiently
      inhibited by their specific antagonists, we found no evidence for "cross
      antagonism" in which an antagonist for receptor "A" blocks responses through
      receptor "B." Such inhibition would have been expected were the dominant negative
      signaling hypothesis correct, and alternative models for TCR antagonism are
      discussed.

PMID- 10201891
TI  - Cutting edge: species specificity of the CC chemokine 6Ckine signaling through
      the CXC chemokine receptor CXCR3: human 6Ckine is not a ligand for the human or
      mouse CXCR3 receptors.
AB  - The CC chemokine known as 6Ckine (SLC, Exodus-2, or TCA4) has been identified as
      a ligand for CCR7. Mouse 6Ckine has also been shown to signal through mouse CXCR3
      and share some of the activities of IFN-gamma inducible protein 10 and monokine
      induced by IFN-gamma. Nonetheless, human 6Ckine has not been shown to bind CXCR3
      receptor or have angiostatic activity. In this study, we report that human 6Ckine
      does not induce a calcium flux in either human CXCR3 or mouse CXCR3 transfected
      cells, although it is an equally potent agonist as mouse 6Ckine and human
      macrophage inflammatory protein-3beta in human CCR7 transfected cells. Mouse
      6Ckine (but not human 6Ckine) is capable of competing with radiolabeled IFN-gamma
      inducible protein 10 for human CXCR3. In addition, radiolabeled human 6Ckine does
      not bind to either human CXCR3 or mouse CXCR3. Together these data suggest that
      human CC chemokine 6Ckine is not a ligand for the human or mouse CXC chemokine
      receptor CXCR3.

PMID- 10201893
TI  - Mice with IFN-gamma receptor deficiency are less susceptible to experimental
      autoimmune myasthenia gravis.
AB  - IFN-gamma can either adversely or beneficially affect certain experimental
      autoimmune diseases. To study the role of IFN-gamma in the autoantibody-mediated
      experimental autoimmune myasthenia gravis (EAMG), an animal model of myasthenia
      gravis in humans, IFN-gammaR-deficient (IFN-gammaR-/-) mutant C57BL/6 mice and
      congenic wild-type mice were immunized with Torpedo acetylcholine receptor (AChR)
      plus CFA. IFN-gammaR-/- mice exhibited significantly lower incidence and severity
      of muscle weakness, lower anti-AChR IgG Ab levels, and lower Ab affinity to AChR
      compared with wild-type mice. Passive transfer of serum from IFN-gammaR-/- mice
      induced less muscular weakness compared with serum from wild-type mice. In
      contrast, numbers of lymph node cells secreting IFN-gamma and of those expressing
      IFN-gamma mRNA were strongly augmented in the IFN-gammaR-/- mice, reflecting a
      failure of negative feedback circuits. Cytokine studies by in situ hybridization
      revealed lower levels of lymphoid cells expressing AChR-reactive IL-1beta and TNF
      alpha mRNA in AChR + CFA-immunized IFN-gammaR-/- mice compared with wild-type
      mice. No differences were found for AChR-reactive cells expressing IL-4, IL-10,
      or TGF-beta mRNA. These results indicate that IFN-gamma promotes systemic humoral
      responses in EAMG by up-regulating the production and the affinity of anti-AChR
      autoantibodies, thereby contributing to susceptibility to EAMG in C57BL/6-type
      mice.

PMID- 10201892
TI  - Cutting edge: SOCS-1 is a potent inhibitor of IL-4 signal transduction.
AB  - IL-4 is an important regulator of the activation, proliferation, and
      differentiation of many hematopoetic cells. Many of these biological effects
      result from the activation of Janus kinases (JAK)1 and JAK3 and the transcription
      factor Stat6. Recent data suggest that members of the SOCS (suppressor of
      cytokine signaling) family of proteins can inhibit JAK-STAT signaling. We have
      examined the ability of SOCS family members to suppress IL-4 signaling, and we
      have found that SOCS-1 potently inhibits the activation of JAK1 kinase and Stat6
      in response to IL-4. Furthermore, SOCS-1 can inhibit the induction of CD23
      expression by IL-4. SOCS-2 does not inhibit induction of signaling by IL-4, while
      inhibition of IL-4 signaling by SOCS-3 can be detected in transient transfection
      systems, but not in stable cell lines. These studies implicate SOCS-1 in
      modulation of IL-4 signaling and suggest that SOCS-1 may play a role in
      regulating the immune response.

PMID- 10201894
TI  - Activation of CD4 T cells by somatic transgenesis induces generalized immunity of
      uncommitted T cells and immunologic memory.
AB  - Cellular immune responses were analyzed in vivo after a single intraspleen
      inoculation of DNA coding for a 12-residue Th cell determinant associated with a
      12-residue B cell epitope, a process termed somatic transgene immunization. We
      show that CD4 T cells are readily activated and produce IL-2, IFN-gamma and IL-4,
      characteristics of an uncommitted phenotype. Linked recognition of the two
      epitopes coded in the same transgene promoted IgM-IgG1 switch and enhanced the
      total Ab response but had no effect on IgG2a Abs. Although originating in the
      spleen, T cell responsiveness was found to spread immediately and with similar
      characteristics to all lymph nodes in the body. A single inoculation was also
      effective in establishing long term immunologic memory as determined by limiting
      dilution analysis, with memory T cells displaying a cytokine profile different
      from that of primary effector T cells. These studies provide evidence that by
      initiating immunity directly in secondary lymphoid organs, an immune response is
      generated with characteristics that differ from those using vaccines of
      conventional DNA or protein in adjuvant administered in peripheral sites. Somatic
      transgene immunization can therefore be used to probe T cell responsiveness in
      vivo and represents a tool to further understanding of the nature of the adaptive
      immune response.

PMID- 10201895
TI  - Naive human CD4+ T cells are a major source of lymphotoxin alpha.
AB  - It is generally accepted that immunologically naive T cells display a very
      restricted cytokine production profile consisting mainly of IL-2, which is used
      as an autocrine growth factor. Here we report that activated naive CD4+ T cells,
      of neonatal or adult origin, express very high levels of soluble lymphotoxin (LT)
      alpha (LTalpha3), as determined by ELISA, RNase protection assay, and
      intracytoplasmic staining. Besides LTalpha3 and IL-2, these cells also produce
      high levels of TNF-alpha together with significant amounts of IFN-gamma and IL
      13. Naive cells also express LTbeta mRNA and the membrane form of LTalpha
      (LTalphabeta). On average, naive CD4+ T cells secrete four times more LTalpha3
      than Th1-like cells, twice more than naive CD8+ T cells, and ten times more than
      B cells. Thus, naive T cells express a large spectrum of cytokines, mainly of the
      Th1 type, and the very high levels of LTalpha3/TNF-alpha that they release may
      play an hitherto unsuspected role in the early stage of T cell-dependent immune
      responses.

PMID- 10201896
TI  - Survival of naive CD4 T cells: roles of restricting versus selecting MHC class II
      and cytokine milieu.
AB  - The diversity of naive CD4 T cells plays an important role in the adaptive immune
      response by ensuring the capability of responding to novel pathogens. In the
      past, it has been generally accepted that naive CD4 T cells are intrinsically
      long-lived; however, there have been studies suggesting some CD4 T cells are
      short-lived. In this report, we identify two populations of naive CD4 T cells: a
      long-lived population as well as a short-lived population. In addition, we
      identify two factors that contribute to the establishment of long-lived naive CD4
      T cells. We confirm earlier findings that MHC class II interaction with the TCR
      on CD4 T cells is important for survival. Furthermore, we find that MHC class II
      alleles with the correct restriction element for Ag presentation mediate the
      peripheral survival of naive CD4 T cells more efficiently than other positively
      selecting alleles, regardless of the selecting MHC in the thymus. The second
      component contributing to the survival of naive CD4 T cells is contact with the
      cytokines IL-4 and IL-7. We find that the physiological levels of IL-4 and IL-7
      serve to enhance the MHC class II-mediated survival of naive CD4 T cells in vivo.

PMID- 10201897
TI  - TCR signaling thresholds regulating T cell development and activation are
      dependent upon SHP-1.
AB  - An examination of thymocytes and peripheral T cells from SHP-1-deficient
      motheaten mice possessing a transgenic MHC class I-restricted TCR has implicated
      SHP-1 in regulating TCR signaling thresholds at three checkpoints in T cell
      development and activation. First, in the population of CD4-CD8- double negative
      thymocytes, SHP-1 appears capable of regulating signals from TCR complexes that
      control the maturation and proliferation of double negative thymocytes. Second,
      the loss of SHP-1 increased the number of CD4+CD8+ double positive thymocytes
      capable of maturing as TCRhigh single positive thymocytes. Third, the loss of SHP
      1 altered the basal level of activation of naive lymph node T cells. Accordingly,
      SHP-1-deficient lymph node T cells bearing the transgenic TCR demonstrated a
      hyperresponsiveness to stimulation with cognate peptide. However, the loss of SHP
      1 did not alter the cytolytic ability of mature effector cytotoxic T lymphocytes.
      Together these results suggest that SHP-1 contributes to establishing thresholds
      for TCR signaling in thymocytes and naive peripheral T cells.

PMID- 10201898
TI  - Factors associated with the development of neonatal tolerance after the
      administration of a plasmid DNA vaccine.
AB  - A plasmid DNA vaccine encoding the circumsporozoite protein of malaria (pCSP)
      induces tolerance rather than immunity when administered to newborn mice. We find
      that this tolerance persists for >1 yr after neonatal pCSP administration and
      interferes with the induction of protective immunity in animals challenged with
      live sporozoites. Susceptibility to tolerance induction wanes rapidly with age,
      disappearing within 1 wk of birth. Higher doses of plasmid are more tolerogenic,
      and susceptibility to tolerance is not MHC-restricted. CD8+ T cells from tolerant
      mice suppress the in vitro Ag-specific immune response of cells from adult mice
      immunized with pCSP. Similarly, CD8+ T cells from tolerant mice transfer
      nonresponsiveness to naive syngeneic recipients. These findings clarify the
      cellular basis and factors contributing to the development of DNA vaccine-induced
      neonatal tolerance.

PMID- 10201899
TI  - p38 mitogen-activated protein kinase mediates signal integration of TCR/CD28
      costimulation in primary murine T cells.
AB  - Optimal T cell activation requires two signals, one generated by TCR and another
      by the CD28 costimulatory receptor. In this study, we investigated the regulation
      of costimulation-induced mitogen-activated protein kinase (MAPK) activation in
      primary mouse T cells. In contrast to that reported for human Jurkat T cells, we
      found that p38 MAPK, but not Jun NH2-terminal kinase (JNK), is weakly activated
      upon stimulation with either anti-CD3 or anti-CD28 in murine thymocytes and
      splenic T cells. However, p38 MAPK is activated strongly and synergistically by
      either CD3/CD28 coligation or PMA/Ca2+ ionophore stimulation, which mimics TCR
      CD3/CD28-mediated signaling. Activation of p38 MAPK correlates closely with the
      stimulation of T cell proliferation. In contrast, PMA-induced JNK activation is
      inhibited by Ca2+ ionophore. T cell proliferation and production of IL-2, IL-4,
      and IFN-gamma induced by both CD3 and CD3/CD28 ligation and the nuclear
      expression of the c-Jun and ATF-2 proteins are each blocked by the p38 MAPK
      inhibitor SB203580. Our findings demonstrate that p38 MAPK 1) plays an important
      role in signal integration during costimulation of primary mouse T cells, 2) may
      be involved in the induction of c-Jun activation and augmentation of AP-1
      transcriptional activity, and 3) regulates whether T cells enter a state of
      functional unresponsiveness.

PMID- 10201900
TI  - Common intra-articular T cell expansions in patients with reactive arthritis:
      identical beta-chain junctional sequences and cytotoxicity toward HLA-B27.
AB  - Spondyloarthropathies constitute a group of autoimmune diseases of special
      interest because of their tight association with the MHC class I molecule HLA-B27
      and the bacterial triggering of some clinical forms called reactive arthritis
      (ReA). One current hypothesis is the presentation by HLA-B27 of a so-called
      arthritogenic peptide to T cells. To better focus on the relevant T cell
      populations within the joint, we performed an extensive beta-chain T cell
      repertoire analysis of synovial fluid compared with PBL in seven patients, four
      of whom were characterized as having ReA triggered by Yersinia enterocolitica,
      Chlamydia trachomatis, or Shigella sonnei. Analysis of the size diversity of the
      beta-chain complementarity-determining region 3 (CDR3) allowed us to evaluate the
      degree of T cell clonality in the samples. Oligoclonal T cell expansions were
      frequently observed in the joint. In one patient, CDR3 amino acid sequences of
      major expansions using two different BV genes were identical. One dominant T cell
      expansion and several CDR3 amino acid sequences were identical in two different
      patients. Furthermore, one sequence was identical with a sequence reported
      independently in a Salmonella-induced ReA patient. Together, these data indicate
      a surprisingly high degree of conservation in the T cell responses in recent
      onset ReA triggered by different micro-organisms. A CD8+ synovial line expressing
      shared clonotypes was established and reacted toward several B*2705
      lymphoblastoid cell lines, therefore supporting a molecular mimicry phenomenon at
      the T cell level in the disease mechanism.

PMID- 10201901
TI  - Chemokine receptor responses on T cells are achieved through regulation of both
      receptor expression and signaling.
AB  - To address the issues of redundancy and specificity of chemokines and their
      receptors in lymphocyte biology, we investigated the expression of CC chemokine
      receptors CCR1, CCR2, CCR3, CCR5, CXCR3, and CXCR4 and responses to their ligands
      on memory and naive, CD4 and CD8 human T cells, both freshly isolated and after
      short term activation in vitro. Activation through CD3 for 3 days had the most
      dramatic effects on the expression of CXCR3, which was up-regulated and
      functional on all T cell populations including naive CD4 cells. In contrast, the
      effects of short term activation on expression of other chemokine receptors was
      modest, and expression of CCR2, CCR3, and CCR5 on CD4 cells was restricted to
      memory subsets. In general, patterns of chemotaxis in the resting cells and
      calcium responses in the activated cells corresponded to the patterns of receptor
      expression among T cell subsets. In contrast, the pattern of calcium signaling
      among subsets of freshly isolated cells did not show a simple correlation with
      receptor expression, so the propensity to produce a global rise in the
      intracellular calcium concentration differed among the various receptors within a
      given T cell subset and for an individual receptor depending on the cell where it
      was expressed. Our data suggest that individual chemokine receptors and their
      ligands function on T cells at different stages of T cell
      activation/differentiation, with CXCR3 of particular importance on newly
      activated cells, and demonstrate T cell subset-specific and activation state
      specific responses to chemokines that are achieved by regulating receptor
      signaling as well as receptor expression.

PMID- 10201902
TI  - TCR engagement regulates differential responsiveness of human memory T cells to
      Fas (CD95)-mediated apoptosis.
AB  - In this work, we have tried to establish whether human memory T cells may be
      protected from Fas (CD95)-induced apoptosis when correctly activated by Ag, and
      not protected when nonspecifically or incorrectly activated. In particular, we
      wanted to investigate the molecular mechanisms that regulate the fate of memory T
      cells following an antigenic challenge. To address this issue, we chose an
      experimental system that closely mimics physiological T cell activation such as
      human T cell lines and clones specific for viral peptides or alloantigens. We
      demonstrate that memory T cells acquire an activation-induced cell death (AICD)
      resistant phenotype when TCRs are properly engaged by specific Ag bound to MHC
      molecules. Ag concentration and costimulation are critical parameters in
      regulating the protective effect. The analysis of the mechanisms involved in the
      block of CD95 signal transduction pathways revealed that the crucial events are
      the inhibition of CD95-associated IL-1beta-converting enzyme (ICE)-like protease
      (FLICE) activation and poly(ADP)-ribose polymerase cleavage, and the mRNA
      expression of FLICE-like inhibitory protein. Furthermore, we have observed that
      TCR-mediated neosynthesis of FLICE-like inhibitory protein mRNA is suppressed
      either by protein tyrosine kinase inhibitors or cyclosporin A. In conclusion, the
      present analysis of the effects of TCR triggering on the regulation of AICD
      suggests that AICD could be inhibited in human memory T cells activated in vivo
      by a foreign Ag, but may become operative when the Ag has been cleared.

PMID- 10201903
TI  - The CC chemokine receptor-7 ligands 6Ckine and macrophage inflammatory protein-3
      beta are potent chemoattractants for in vitro- and in vivo-derived dendritic
      cells.
AB  - Dendritic cell migration to secondary lymphoid tissues is critical for Ag
      presentation to T cells necessary to elicit an immune response. Despite the
      importance of dendritic cell trafficking in immunity, at present little is
      understood about the mechanisms that underlie this phenomenon. Using a novel
      transwell chemotaxis assay system, we demonstrate that the CC chemokine receptor
      7 (CCR7) ligands 6Ckine and macrophage inflammatory protein (MIP)-3 beta are
      selective chemoattractants for MHC class IIhigh B7-2high bone marrow-derived
      dendritic cells at a potency 1000-fold higher than their known activity on naive
      T cells. Furthermore, these chemokines stimulate the chemotaxis of freshly
      isolated lymph node dendritic cells, as well as the egress of skin dendritic
      cells ex vivo. Because these chemokines are expressed in lymphoid organs and
      6Ckine has been localized to high endothelial venules and lymphatic endothelium,
      we propose that they may play an important role in the homing of dendritic cells
      to lymphoid tissues.

PMID- 10201904
TI  - Extracellular signal-regulated kinase, stress-activated protein kinase/c-Jun N
      terminal kinase, and p38mapk are involved in IL-10-mediated selective repression
      of TNF-alpha-induced activation and maturation of human peripheral blood monocyte
      derived dendritic cells.
AB  - TNF-alpha or IL-10 has been implicated to reversibly regulate physiological
      states of dendritic cells (DCs). However, little is known about dual stimulations
      of these cytokines on DC properties and the intracellular signaling events that
      are responsible for the regulation of these states. Here, we show that a family
      of mitogen-activated protein kinases (MAPKs), extracellular signal-regulated
      kinase 2 (ERK2), stress-activated protein kinase/c-Jun N-terminal kinase
      (SAPK/JNK), and p38mapk, are potentially involved in IL-10-mediated selective
      suppression of TNF-alpha-induced changes of the monocyte-derived DC properties.
      TNF-alpha induced the cluster formation of the cells and the enhancement of cell
      surface expression levels of CD83, CD86, and HLA-DR, and T cell stimulatory
      capacity, whereas the capacities for the endocytosis and the chemotactic
      migration were suppressed in these cells. Treatment of monocyte-derived DCs with
      IL-10 resulted in the reduction of the cell surface expression levels of CD86,
      HLA-DR, and T cell stimulatory capacity, whereas both endocytic and chemotactic
      migratory capacities were increased by IL-10. Dual stimulations of monocyte
      derived DCs with TNF-alpha and IL-10 selectively antagonized their respective
      effects on these DC properties. TNF-alpha induced tyrosine phosphorylation and
      enzymatic activation of ERK2, SAPK/JNK, and p38mapk, whereas IL-10 did not induce
      these events. Dual stimulations of TNF-alpha plus IL-10 abolished TNF-alpha
      induced changes of these MAPKs in DCs. These results suggest that the blockage in
      the MAPKs cascades contributes to IL-10-mediated repression of TNF-alpha-induced
      changes of DC properties.

PMID- 10201906
TI  - T1/ST2 expression is enhanced on CD4+ T cells from schistosome egg-induced
      granulomas: analysis of Th cell cytokine coexpression ex vivo.
AB  - Th cells are categorized into subsets based on the cytokine production of in
      vitro-differentiated Th populations. For in vivo-differentiated Th subsets,
      little is known about the heterogeneity of cytokine production in single cells.
      We recently described a molecule, T1/ST2, that is preferentially expressed on the
      surface of Th2 cells. Here we combined high-gradient magnetic cell separation
      with four-color single-cell cytometry to analyze simultaneously three
      intracellular cytokines and T1/ST2 surface expression on CD4+ cells from lungs
      containing granulomas induced by Schistosoma mansoni eggs. T1/ST2 was highly up
      regulated on CD4+ T cells from hepatic granulomas and granulomatous lungs.
      T1/ST2+ cells from granulomatous lungs preferentially produced type 2 cytokines
      ex vivo. In the total CD4+ population, coexpression of type 1 and type 2
      cytokines occurred frequently. However, such coproduction was drastically reduced
      in T1/ST2+ cells compared with T1/ST2- cells. Coexpression of type 1 and type 2
      cytokines was also rare in cells simultaneously producing two cytokines of one
      type. These findings indicate that individual CD4+ T cells in vivo have different
      levels of commitment to a certain Th phenotype. Coexpression of two type 2
      cytokines or production of one type 2 cytokine together with surface expression
      of T1/ST2 indicate advanced commitment to the Th2 phenotype.

PMID- 10201905
TI  - Factors regulating stem cell recruitment to the fetal thymus.
AB  - Colonization of the thymic rudiment during development is initiated before
      vascularization so that hemopoietic precursors must leave the pharyngeal vessels
      and migrate through the perithymic mesenchyme to reach the thymus, suggesting
      that they may be responding to a gradient of chemoattractant factors. We report
      that diffusible chemoattractants are produced by MHC class II+ epithelial cells
      of the fetal thymus, and that the response of precursors to these factors is
      mediated via a G protein-coupled receptor, consistent with factors being members
      of the chemokine family. Indeed, a number of chemokine receptors are expressed by
      thymic precursors, and several chemokines are also expressed by thymic epithelial
      cells. However, these chemokines are also expressed in a tissue that is unable to
      attract precursors, although the thymus expressed chemokine, TECK, is expressed
      at higher levels in thymic epithelial cells and we show that it has chemotactic
      activity for isolated thymic precursors. Neutralizing Ab to TECK, however, did
      not prevent thymus recolonization by T cell precursors, suggesting that other
      novel chemokines might be involved in this process. In addition, we provide
      evidence for the involvement of matrix metalloproteinases in chemoattractant
      mediated T cell precursor recruitment to the thymus during embryogenesis.

PMID- 10201907
TI  - Absence of Peyer's patches and abnormal lymphoid architecture in chronic
      proliferative dermatitis (cpdm/cpdm) mice.
AB  - The chronic proliferative dermatitis (cpdm) mutation causes inflammation in
      multiple organs, most prominently in the skin. Examination of the immune system
      revealed severe abnormalities in the architecture of lymphoid tissues. Peyer's
      patches were absent. In contrast, the spleen, lymph nodes, and nasal-associated
      lymphoid tissues were present. The spleen had normal numbers of T and B cells,
      but the spleen, lymph nodes, and nasal-associated lymphoid tissues had poorly
      defined follicles and lacked germinal centers and follicular dendritic cells. The
      marginal zone in the spleen was absent. The total concentration of serum IgG,
      IgA, and IgE in cpdm/cpdm mice was significantly decreased, whereas serum IgM was
      normal. Fecal IgA was low to undetectable in mutant mice, and the concentration
      of fecal IgM was increased. The titer of DNP-specific Abs following immunization
      with DNP-keyhole limpet hemocyanin was significantly decreased for all IgG
      subclasses. In contrast, T cell function appeared normal as assessed by
      evaluation of the contact hypersensitivity response in cpdm/cpdm mice. The cpdm
      mutation causes a complex phenotype that is characterized by multiorgan
      inflammation and the defective development of lymphoid tissues. The cpdm/cpdm
      mouse may be a useful model to study the factors that control the development of
      lymphoid tissues, in particular the Peyer's patches, and the mechanisms that
      control the humoral immune response.

PMID- 10201908
TI  - JAK3, STAT, and MAPK signaling pathways as novel molecular targets for the
      tyrphostin AG-490 regulation of IL-2-mediated T cell response.
AB  - AG-490 is a member of the tyrphostin family of tyrosine kinase inhibitors. While
      AG-490 has been considered to be a Janus kinase (JAK)2-specific inhibitor, these
      conclusions were primarily drawn from acute lymphoblastic leukemia cells that
      lack readily detectable levels of JAK3. In the present study, evidence is
      provided that clearly demonstrates AG-490 potently suppresses IL-2-induced T cell
      proliferation, a non-JAK2-dependent signal, in a dose-dependent manner in T cell
      lines D10 and CTLL-2. AG-490 blocked JAK3 activation and phosphorylation of its
      downstream counterpart substrates, STATs. Inhibition of JAK3 by AG-490 also
      compromised the Shc/Ras/Raf/mitogen-activated protein kinase (MAPK) signaling
      pathways as measured by phosphorylation of Shc and extracellular signal-related
      kinase 1 and 2 (ERK1/2). AG-490 effectively inhibited tyrosine phosphorylation
      and DNA binding activities of several transcription factors including STAT1, -3, 
      5a, and -5b and activating protein-1 (AP-1) as judged by Western blot analysis
      and electrophoretic mobility shift assay. These data suggest that AG-490 is a
      potent inhibitor of the JAK3/STAT, JAK3/AP-1, and JAK3/MAPK pathways and their
      cellular consequences. Taken together, these findings support the notion that AG
      490 possesses previously unrecognized clinical potential as an immunotherapeutic
      drug due to its inhibitory effects on T cell-derived signaling pathways.

PMID- 10201909
TI  - Selection of CD8+ T cells with highly focused specificity during viral
      persistence in the central nervous system.
AB  - The relationships between T cell populations during primary viral infection and
      persistence are poorly understood. Mice infected with the neurotropic JHMV strain
      of mouse hepatitis virus mount potent regional CTL responses that effectively
      reduce infectious virus; nevertheless, viral RNA persists in the central nervous
      system (CNS). To evaluate whether persistence influences Ag-specific CD8+ T
      cells, functional TCR diversity was studied in spleen and CNS-derived CTL
      populations based on differential recognition of variant peptides for the
      dominant nucleocapsid epitope. Increased specificity of peripheral CTL from
      persistently infected mice for the index epitope compared with immunized mice
      suggested T cell selection during persistence. This was confirmed with CD8+ T
      cell clones derived from the CNS of either acutely (CTLac) or persistently
      (CTLper) infected mice. Whereas CTLac clones recognized a broad diversity of
      amino acid substitutions, CTLper clones exhibited exquisite specificity for the
      wild-type sequence. Highly focused specificity was CD8 independent but correlated
      with longer complementarity-determining regions 3 characteristic of CTLper
      clonotypes despite limited TCR alpha/beta-chain heterogeneity. Direct ex vivo
      analysis of CNS-derived mononuclear cells by IFN-gamma enzyme-linked immunospot
      assay confirmed the selection of T cells with narrow Ag specificity during
      persistence at the population level. These data suggest that broadly reactive CTL
      during primary infection are capable of controlling potentially emerging
      mutations. By contrast, the predominance of CD8+ T cells with dramatically
      focused specificity during persistence at the site of infection and in the
      periphery supports selective pressure driven by persisting Ag.

PMID- 10201910
TI  - Utilization of MHC class I transgenic mice for development of minigene DNA
      vaccines encoding multiple HLA-restricted CTL epitopes.
AB  - We engineered a multiepitope DNA minigene encoding nine dominant HLA-A2.1- and
      A11-restricted epitopes from the polymerase, envelope, and core proteins of
      hepatitis B virus and HIV, together with the PADRE (pan-DR epitope) universal Th
      cell epitope and an endoplasmic reticulum-translocating signal sequence.
      Immunization of HLA transgenic mice with this construct resulted in: 1)
      simultaneous CTL induction against all nine CTL epitopes despite their varying
      MHC binding affinities; 2) CTL responses that were equivalent in magnitude to
      those induced against a lipopeptide known be immunogenic in humans; 3) induction
      of memory CTLs up to 4 mo after a single DNA injection; 4) higher epitope
      specific CTL responses than immunization with DNA encoding whole protein; and 5)
      a correlation between the immunogenicity of DNA-encoded epitopes in vivo and the
      in vitro responses of specific CTL lines against minigene DNA-transfected target
      cells. Examination of potential variables in minigene construct design revealed
      that removal of the PADRE Th cell epitope or the signal sequence, and changing
      the position of selected epitopes, affected the magnitude and frequency of CTL
      responses. Our results demonstrate the simultaneous induction of broad CTL
      responses in vivo against multiple dominant HLA-restricted epitopes using a
      minigene DNA vaccine and underline the utility of HLA transgenic mice in
      development and optimization of vaccine constructs for human use.

PMID- 10201911
TI  - Antibodies to the IL-12 receptor beta 2 chain mark human Th1 but not Th2 cells in
      vitro and in vivo.
AB  - Great attention has been placed on the possibility of distinguishing Th1 from Th2
      cells on the basis of differential expression of surface receptors. We have
      recently shown that the differential expression of the IL-12R beta 2 chain in Th1
      and Th2 cells, as measured at the mRNA level, accounts for an important
      regulatory mechanism in the differentiation of the two cell subsets. In this
      study, we identify IL-12R expression at the protein level. We have generated an
      anti-IL-12R beta 2-specific mAb and analyzed IL-12R beta 2 expression on
      polarized Th cell populations generated in vitro and on T cells derived from
      patients with Th1- or Th2-mediated inflammatory conditions. Although IL-12R beta
      2 was absent in freshly isolated PBMC and in cord blood cells, we were able to
      detect IL-12R beta 2 expression selectively in differentiated Th1 and T cytotoxic
      1, but not Th2 or T cytotoxic 2 cells. In the presence of IL-12, cell surface
      expression of the IL-12R beta 2 subunit was readily detected on T cells after 24
      h, reached the maximum at day 5, and declined thereafter. Most importantly, the
      anti-IL-12R beta 2 mAb recognizes lung T cells from patients with sarcoidosis, a
      disease characterized by a typical cell-mediated, Th1-type inflammatory response.
      In contrast, IL-12R beta 2 was absent in lung T cells from patients with allergic
      asthma, a disease characterized by a Th2-type inflammatory response. The mAb
      reported in this study should represent a powerful tool to investigate the role
      of Th1 and Th2 cells in inflammatory conditions and to monitor therapies aimed at
      altering the balance of Th cell subsets.

PMID- 10201912
TI  - Cross-recognition of two middle T protein epitopes by immunodominant polyoma
      virus-specific CTL.
AB  - We recently identified the immunodominant epitope for polyoma virus-specific CTL
      as the Dk-associated peptide MT389-397 derived from the middle T (MT) viral
      oncoprotein. Another Dk-restricted peptide corresponding to residues 236-244 of
      MT was recognized by nearly all MT389-397-reactive CTL clones, but required
      concentrations at least 2 logs higher to sensitize syngeneic target cells for
      lysis. Except for identity at the three putative Dk-peptide anchor residues,
      MT236-244 shares no homology with MT389-397. Using a novel europium-based class I
      MHC-peptide binding immunoassay, we determined that MT236-244 bound Dk 2-3 logs
      less well than MT389-397. Infection with a mutant polyoma virus whose MT is
      truncated just before the MT389-397 epitope or immunization with MT389-397 or
      MT236-244 peptides elicited CTL that recognized both MT389-397 and MT236-244.
      Importantly, infection with a polyoma virus lacking MT389-397 and mutated in an
      MT236-244 Dk anchor position induced polyoma virus-specific CTL recognizing
      neither MT389-397 nor MT236-244 epitopes. Despite predominant usage of the Vbeta6
      gene segment, MT389-397/MT236-244 cross-reactive CTL clones possess diverse
      complementarity-determining region 3beta domains; this is functionally reflected
      in their heterogeneous recognition patterns of alanine-monosubstituted MT389-397
      peptides. Using Dk/MT389-397 tetramers, we directly visualized MT236-244 peptide
      induced TCR down-modulation of virtually all MT389-397-specific CD8+ T cells
      freshly explanted from polyoma-infected mice, suggesting that a single TCR
      recognizes both Dk-restricted epitopes. The availability of immunodominant
      epitope-specific CTL capable of recognizing a second epitope in MT, a viral
      protein essential for tumorigenesis, may serve to amplify the CTL response to the
      immunodominant epitope and prevent the emergence of immunodominant epitope-loss
      viruses and virus-induced tumors.

PMID- 10201913
TI  - Adjuvant-guided type-1 and type-2 immunity: infectious/noninfectious dichotomy
      defines the class of response.
AB  - Traditionally, protein Ags have been injected in CFA (oil with inactivated
      mycobacteria) to induce immunity and with IFA (oil alone) to induce tolerance. We
      report here that injection of hen eggwhite lysozyme, a prototypic Ag, in CFA
      induced and IFA-induced pools of hen eggwhite lysozyme-specific memory T cells of
      comparable fine specificity, clonal size, and avidity spectrum, but with type-1
      and type-2 cytokine signatures, respectively. This adjuvant-guided induction of
      virtually unipolar type-1 and type-2 immunity was observed with seven protein Ags
      and in a total of six mouse strains. Highly polarized type-1 and type-2 immunity
      are thus readily achievable through the choice of adjuvant, irrespective of the
      genetic bias of the host and of the nature of the protein Ag. This finding should
      have far-reaching implications for the development of vaccines against infectious
      and autoimmune diseases. Furthermore, our demonstration that Ag injected with IFA
      is as strongly immunogenic for T cells as it is with CFA shows that the presence
      of the mycobacteria determines not the priming of naive T cells through the
      second-signal link but the path of downstream differentiation toward CD4 memory
      cells that express either type-1 or type-2 cytokines.

PMID- 10201914
TI  - Reconciling repertoire shift with affinity maturation: the role of deleterious
      mutations.
AB  - The shift in Ab repertoire, from Abs dominating certain primary B cell responses
      to genetically unrelated Abs dominating subsequent "memory" responses, challenges
      the accepted paradigm of affinity maturation. We used mathematical modeling and
      computer simulations of the dynamics of B cell responses, hypermutation,
      selection, and memory cell formation to test hypotheses attempting to explain
      repertoire shift. We show that repertoire shift can be explained within the
      framework of the affinity maturation paradigm, only when we recognize the
      destructive nature of hypermutation: B cells with a high initial affinity for the
      Ag are less likely to improve through random mutations.

PMID- 10201915
TI  - Increased generation of CD8+ T cell clones in p53 mutant mice.
AB  - Very few cultured CD8+ T cell clones can normally be obtained from a single mouse
      and maintained in long-term culture. To improve the yield, we immunized p53
      mutant mice with peptides of Sendai virus (FAPGNYPAL) and influenza virus
      (ASNENMETM) origin. Substantially more clones could be derived from p53-/- mice
      than from similarly treated wild-type mice (p53+/+); an intermediate yield was
      obtained from heterozygous mice (p53+/-). CTL lines or clones from p53-/- mice
      exhibited greater proliferative activity and resistance to gamma-irradiation than
      those from p53+/+ mice, and were cytolytically potent.

PMID- 10201916
TI  - Modulation of monocytic cell activity and virus susceptibility during
      differentiation into macrophages.
AB  - A major component of innate immune responses relies on monocytes and macrophages,
      virus infection of which will pose a particular problem for immunological
      defense. Consequently, the monocytic cell differentiation pathway was analyzed in
      terms of cellular modulations therein and their relation to monocytotropic virus
      infection. Differentiation was characterized by down-regulation of CD14, MHC Ags,
      the monocytic SWC1 marker, and p53; concomitant up-regulation of the SWC9
      macrophage marker, a putative porcine CD80 (detected with anti-human CD80 Ab),
      and acid phosphatase secretion were also characteristic. Elevated phagocytic and
      endocytic activities as well as endosomal/lysosomal acidification were identified
      as being important to the macrophage. In contrast, monocytes possessed high
      accessory activity. This was multifactorial, concomitantly requiring 1) high MHC
      Ag expression; 2) enzyme activity of esterase, peroxidase, myeloperoxidase, and
      5' nucleotidase in preference to glucosidase, galactosidase, and glucuronidase;
      and 3) elevated capacity for spontaneous IL-1 production. Only with all
      parameters was efficient stimulation of Ag-specific lymphocytes possible. These
      results point to a continuous process during differentiation, involving inter
      related characteristics linking the more accessory monocyte to the scavenger
      macrophage, both in vitro and in vivo. Of particular interest was how these
      characteristics related to monocytotropic virus infection, and how a particular
      virus could show a clear preference for the differentiating macrophages. Such
      results not only further our understanding of porcine immunology, but also
      provide evidence and a potential model for the determination and characterization
      of monocytotropic virus-host cell interactions.

PMID- 10201917
TI  - Three different MHC class I molecules bind the same CTL epitope of the influenza
      virus in a primate species with limited MHC class I diversity.
AB  - One of the most remarkable features of the MHC class I loci of most outbred
      mammalian populations is their exceptional diversity, yet the functional
      importance of this diversity remains to be fully understood. The cotton-top
      tamarin (Saguinus oedipus) is unusual in having MHC class I loci that exhibit
      both limited polymorphism and sequence variation. To investigate the functional
      implications of limited MHC class I diversity in this outbred primate species, we
      infected five tamarins with influenza virus and defined the CTL epitopes
      recognized by each individual. In addition to an immunodominant epitope of the
      viral nucleoprotein (NP) that was recognized by all individuals, two tamarins
      also made a response to the same epitope of the matrix (M1) protein.
      Surprisingly, these two tamarins used different MHC class I molecules, Saoe-G*02
      and -G*04, to present the M1 epitope. In addition, CTLs from one of the tamarins
      recognized target cells that expressed neither Saoe-G*02 nor -G*04, but, rather,
      a third MHC class I molecule, Saoe-G*12. Sequence analysis revealed that Saoe
      G*12 differs from both Saoe-G*02 and -G*04 by only two nucleotides and was
      probably generated by recombination between these two alleles. These results
      demonstrate that at least three of the tamarin's MHC class I molecules can
      present the same epitope to virus-specific CTLs. Thus, four of the tamarin's 12
      MHC class I molecules bound only two influenza virus CTL epitopes. Therefore, the
      functional diversity of cotton-top tamarin's MHC class I loci may be even more
      limited than their genetic diversity suggests.

PMID- 10201918
TI  - CD69 expression discriminates MHC-dependent and -independent stages of thymocyte
      positive selection.
AB  - In the thymus, phenotypically and functionally mature single positive cells are
      generated from immature CD4+8+ precursors by a process known as positive
      selection. Although this event is known to involve alphabetaTCR ligation by
      peptide/MHC complexes expressed on thymic stromal cells, it is clear that
      positive selection is a multistage process involving transition through an
      intermediate CD4+8+69+ phase as well as subsequent postselection phases. By
      analyzing the development of preselection CD4+8+69- and intermediate CD4+8+69+
      thymocytes in the presence of MHC class I-deficient, MHC class II-deficient, and
      MHC double-deficient thymic stromal cells, we investigated the role of MHC
      molecules at three distinct points during positive selection. Although the
      initiation of positive selection is critically dependent upon MHC interactions,
      we find the that later stages of maturation, involving the differentiation of
      CD4+8- and CD4-8+ cells from CD4+8+69+ thymocytes, occur in the absence of MHC
      molecules. Moreover, an analysis of the postselection proliferation of newly
      generated CD4+8- and CD4-8+ thymocytes shows that this also occurs independently
      of MHC molecules. Thus, our data provide direct evidence that, although positive
      selection is a multistage process initiated by TCR-MHC interactions, continuation
      of this process and subsequent postselection events are independent of ongoing
      engagement of the TCR.

PMID- 10201919
TI  - Gene conversion and hypermutation during diversification of VH sequences in
      developing splenic germinal centers of immunized rabbits.
AB  - The young rabbit appendix and the chicken bursa of Fabricius are primary lymphoid
      organs where the B cell Ab repertoire develops in germinal centers (GCs) mainly
      by a gene conversion-like process. In human and mouse, V-gene diversification by
      somatic hypermutation in GCs of secondary lymphoid organs leads to affinity
      maturation. We asked whether gene conversion, somatic hypermutation, or both
      occur in rabbit splenic GCs during responses to the hapten DNP. We determined DNA
      sequences of rearranged heavy and light chain V region gene segments in single
      cells from developing DNP-specific GCs after immunization with DNP-bovine gamma
      globulin and conclude that the changes at the DNA level that may lead to affinity
      maturation occur by both gene conversion and hypermutation. Selection was
      suggested by finding some recurrent amino acid replacements that may contribute
      increased affinity for antigen in the complementarity-determining region
      sequences of independently evolved clones, and a narrower range of
      complementarity-determining region 3 lengths at day 15. Some of the alterations
      of sequence may also lead to new members of the B cell repertoire in adult
      rabbits comparable with those produced in gut associated lymphoid tissues of
      young rabbits.

PMID- 10201920
TI  - Triggering of effector functions on a CD8+ T cell clone upon the aggregation of
      an activatory CD94/kp39 heterodimer.
AB  - Some T lymphocytes express the CD94 Ag, which is known to form heterodimers with
      members of the NKG2 family. We have studied the expression pattern and function
      of CD94 heterodimers in different alphabeta or gammadelta T cell clones. Most of
      the CD94+NKG2A- T cells have a low to intermediate expression of CD94 Ag. The
      cross-linking of the CD94/NKG2 heterodimer in one of these CD8 alphabeta
      CD94+NKG2A- T cell clones (K14B06) was able to: 1) increase the intracellular
      concentration of Ca2+, 2) induce the up-regulation of CD25 Ag expression and the
      secretion of IFN-gamma, and 3) trigger redirected cytotoxicity in a TCR
      independent manner. This activatory property was not shared by any other
      costimulatory molecule expressed by the K14B06 T cell clone, including CD8, CD28,
      CD45, CD69, or CD2 Ags. The immunoprecipitation of CD94 heterodimer showed a 39
      kDa band with a similar m.w. to the activatory heterodimer found on some NK
      clones. A novel form of the NKG2 family (NKG2H) was identified in K14B06. NKG2H
      protein represents an alternative spliced form of the NKG2E gene, displaying a
      charged residue in the transmembrane portion and a cytoplasmic tail that lacks
      immunoreceptor tyrosine-based inhibitory motifs. The expression of NKG2H in the
      cell membrane through its association to CD94 and DAP-12 molecules supports that
      it could form part of the activatory CD94/Kp39 heterodimer present on K14B06
      cells.

PMID- 10201921
TI  - Recapitulation of normal and abnormal BioBreeding rat T cell development in adult
      thymus organ culture.
AB  - Congenitally lymphopenic diabetes-prone (DP) BioBreeding (BB) rats develop
      spontaneous T cell-dependent autoimmunity. Coisogenic diabetes-resistant (DR) BB
      rats are not lymphopenic and are free of spontaneous autoimmune disease, but
      become diabetic in response to depletion of RT6+ T cells. The basis for the
      predisposition to autoimmunity in BB rats is unknown. Abnormal T cell development
      in DP-BB rats can be detected intrathymically, and thymocytes from DR-BB rats
      adoptively transfer diabetes. The mechanisms underlying these T cell
      developmental abnormalities are not known. To study these processes, we
      established adult thymus organ cultures (ATOC). We report that cultured DR- and
      DP-BB rat thymi generate mature CD4 and CD8 single-positive cells with up
      regulated TCRs. DR-BB rat cultures also generate T cells that express RT6. In
      contrast, DP-BB rat cultures generate fewer CD4+, CD8+, and RT6+ T cells.
      Analysis of the cells obtained from ATOC suggested that the failure of cultured
      DP-BB rat thymi to generate T cells with a mature phenotype is due in part to an
      increased rate of apoptosis. Consistent with this inference, we observed that
      addition of the general caspase inhibitor Z-VAD-FMK substantially increases the
      number of both mature and immature T cells produced by DP-BB rat ATOC. We
      conclude that cultured DR-BB and DP-BB rat thymi, respectively, recapitulate the
      normal and abnormal T cell developmental kinetics and phenotypes observed in
      these animals in vivo. Such cultures should facilitate identification of the
      underlying pathological processes that lead to immune dysfunction and
      autoimmunity in BB rats.

PMID- 10201922
TI  - Administration of an IL-12-encoding DNA plasmid prevents the development of
      chronic graft-versus-host disease (GVHD).
AB  - The transfer of DBA/2 spleen cells into (C57BL/10 x DBA/2)F1 mice induces chronic
      graft-vs-host disease (GVHD), which is characterized by the production of Th2
      cytokines, hypergammaglobulinemia, and immune complex-mediated glomerulonephritis
      like systemic lupus erythematosus. IL-12 strongly induces the production of Th1
      cytokines and reduces Th2 activity in vivo. In this study, the effect of gene
      therapy on the development of murine chronic GVHD was examined using an IL-12
      encoding plasmid (pCAGGSIL-12), with the expectation that it might regulate
      Th1/Th2 activity and have a beneficial impact on the clinical manifestations of
      disease. pCAGGSIL-12 or its p40 antagonist plasmid (pCAGGSp40) were injected i.m.
      every 3 wk in GVHD-induced (C57BL/10 x DBA/2)F1 mice. A total of 100 microg of
      pCAGGSIL-12 improved the Th1/Th2 balance in vivo, suppressed the production of
      IgG, and significantly reduced the development of glomerulonephritis. GVHD was
      exacerbated by injection of the pCAGGSp40 antagonist. Our results demonstrate
      that GVHD can be treated successfully by the administration of an IL-12-encoding
      plasmid, and that such therapy does not induce acute GVHD.

PMID- 10201923
TI  - Human T cells express the C5a receptor and are chemoattracted to C5a.
AB  - The anaphylatoxin C5a is a potent mediator of inflammation that exerts a broad
      range of activity on cells of the myeloid lineage. In this study, we present the
      first evidence that human T cells express the C5a receptor (C5aR) and are
      chemotactic to C5a. Using FACS analysis, we found that the C5aR was expressed at
      a low basal level on unstimulated T cells and was strikingly up-regulated upon
      PHA stimulation in a time- and dose-dependent manner. CD3+ sorted T cells as well
      as Jurkat T cells were shown to express C5aR mRNA as assessed by RT-PCR.
      Moreover, semiquantitative RT-PCR analysis demonstrated that C5aR mRNA was down
      regulated in purified T cells upon long-term PHA stimulation. To demonstrate that
      C5a was biologically active on T cells, we investigated the chemotactic activity
      of C5a and observed that purified CD3+ T cells are chemotactic to C5a at
      nanomolar concentrations. Finally, using a combination of in situ hybridization
      and immunohistochemistry, we showed that the T cells infiltrating the central
      nervous system during experimental allergic encephalomyelitis express the C5aR
      mRNA. In summary, these results suggest that C5a exerts direct effects on T cells
      and could be involved in the trafficking of T cells under physiological and
      pathological conditions, including inflammatory diseases of the central nervous
      system.

PMID- 10201924
TI  - Failure of measles virus to activate nuclear factor-kappa B in neuronal cells:
      implications on the immune response to viral infections in the central nervous
      system.
AB  - Neurons are postmitotic cells that foster virus persistence. These cells lack the
      HLA class I molecules required for clearance of infected cells. Previously, we
      showed that HLA class I is induced by measles virus (MV) on glial cells, which is
      primarily mediated by IFN-beta. In contrast, MV was unable to induce HLA class I
      or IFN-beta in neuronal cells. This failure was associated with lack of NF-kappa
      B binding to the positive regulatory domain II element of the IFN-beta promoter,
      which is essential for virus-induced IFN-beta gene activity. In this study, we
      demonstrate that the failure to activate NF-kappa B in neuronal cells is due to
      the inability of MV to induce phosphorylation and degradation of I kappa B, the
      inhibitor of NF-kappa B. In contrast, TNF-alpha induced degradation of I kappa B
      alpha in the neuronal cells, suggesting that failure to induce I kappa B alpha
      degradation is likely due to a defect in virus-mediated signaling rather than to
      a defect involving neuronal I kappa B alpha. Like MV, mumps virus and dsRNA
      failed to induce I kappa B alpha degradation in the neuronal cells, suggesting
      that this defect may be specific to viruses. Autophosphorylation of the dsRNA
      dependent protein kinase, a kinase possibly involved in virus-mediated I kappa B
      alpha phosphorylation, was intact in both cell types. The failure of virus to
      induce I kappa B alpha phosphorylation and consequently to activate NF-kappa B in
      neuronal cells could explain the repression of IFN-beta and class I gene
      expression in virus-infected cells. These findings provide a potential mechanism
      for the ability of virus to persist in neurons and to escape immune surveillance.

PMID- 10201925
TI  - Stable peptide binding to MHC class II molecule is rapid and is determined by a
      receptive conformation shaped by prior association with low affinity peptides.
AB  - Formation of stable class II MHC/peptide complex involves conformational changes
      and proceeds via an intermediate. Although this intermediate complex forms and
      dissociates in minutes, its conversion to a stable complex is a very slow
      process, taking up to a few days to reach completion. Here, we investigate the
      different steps of this binding and demonstrate that the conformational changes
      necessary to generate a receptive molecule is the rate-determining slow step in
      the process, while formation of the stable MHC/peptide complex is very rapid.
      With HLA-DR1 as our model class II molecule, we first used low affinity variants
      of hemagglutinin peptide (HA306-318), which lack the principal anchor, to shape
      the conformation of the MHC and then studied the kinetics of stable binding of
      HA306-318 to such an induced conformation. We found that the apparent association
      rate of HA306-318 is equivalent to the dissociation rate of the low affinity
      peptide. A 4- to 18-fold enhancement in the binding rates of HA306-318 was
      observed depending on the dissociation rates of the low affinity peptides. These
      results establish that 1) formation of stable MHC/peptide complexes is very rapid
      and 2) prior binding of low affinity peptide induces a receptive conformation in
      MHC for efficient stable peptide binding. Furthermore, in the absence of any free
      peptide, this receptive molecule rapidly reverts to slow binding behavior toward
      the subsequently offered peptide. These results have important implications for
      the roles of low affinity MHC/peptide complexes in Ag presentation.

PMID- 10201926
TI  - Regulation of CD154 (CD40 ligand) mRNA stability during T cell activation.
AB  - The CD154 protein (CD40 ligand), which is critical to the regulation of both
      humoral and cellular immune responses, is expressed transiently on the surface of
      activated CD4+ T cells. To determine whether control of mRNA stability
      contributes to the highly regulated expression of CD154 during T cell activation,
      CD4+ T cells were isolated from human peripheral blood and stimulated for various
      lengths of time with plate-bound anti-CD3 mAb. At early times after anti-CD3
      activation, the CD154 message was found to be very unstable, however, the
      stability measurably increased after 24-48 h of activation. Similar analyses of
      TNF-alpha and c-myc mRNA decay throughout a time course of T cell activation
      revealed patterns of regulation that were distinct from CD154. Similar to the
      effect on TNF-alpha mRNA, stimulation of T cells with PMA + ionomycin greatly
      increased the stability of CD154 message. However, CD154 message stability was
      only modestly increased in T cells coactivated with anti-CD3 and anti-CD28 at 5 h
      and not increased by costimulation at 24 h. Finally, an analysis of both mRNA and
      surface protein expression over a time course of T cell activation with anti-CD3
      revealed a rapid induction of expression early after activation. This induction
      was followed by a more gradual decrease in expression over the next 48 h.
      Together, these data support a role for posttranscriptional regulation in the
      control and overall expression of CD154 in activated T cells.

PMID- 10201927
TI  - Similarities and differences between human and murine TNF promoters in their
      response to lipopolysaccharide.
AB  - Transcription of the TNF gene is rapidly and transiently induced by LPS in cells
      of monocyte/macrophage lineage. Previous data suggested that multiple NF
      kappaB/Rel binding sites play a role in the transcriptional response to LPS of
      the murine gene. However, the relevance of homologous sites in the human TNF gene
      remained a matter of controversy, partly because the high affinity NF-kappaB/Rel
      site located at -510 in the murine promoter is not conserved in humans. Here we
      used two sets of similarly designed human and mouse TNF promoter deletion
      constructs and overexpression of IkappaB in the murine macrophage cell line ANA-1
      to show remarkable similarity in the pattern of the transcriptional response to
      LPS, further demonstrating the functional role of the distal promoter region
      located between -600 and -650. This region was characterized by mutagenesis of
      protein binding sites, including two relatively low affinity NF-kappaB/Rel sites,
      #2 and 2a. Mutation in each of the NF-kappaB sites resulted in 2- to 3-fold lower
      transcriptional activity in response to LPS. In contrast to LPS activation, the
      response to PMA was substantially lower in magnitude and required only the
      proximal promoter region. In summary, the functional topography of human and
      murine promoters when assayed in the same system has some marked similarities.
      Our observations support the notion that full LPS response of TNF gene requires
      both NF-kappaB and non-NF-kappaB nuclear proteins. Our data also suggest that the
      functional activity of a given kappaB site depends on the entire DNA sequence
      context in the promoter region.

PMID- 10201928
TI  - Repression of IL-4-induced gene expression by IFN-gamma requires Stat1
      activation.
AB  - IFN-gamma antagonizes many physiological responses mediated by IL-4, including
      the inhibition of IL-4-induced IgE production. This event is largely mediated at
      the level of transcription. We observed that the IL-4 response element of the
      germline epsilon promoter is sufficient to confer IFN-gamma-mediated repression
      onto a reporter construct. The inhibitory effects were observed in both lymphoid
      and nonlymphoid cell lines. Stat1, which is activated by IFN-gamma, cannot
      recognize the Stat6-specific IL-4 response element in the epsilon promoter.
      Hence, competitive DNA binding does not seem to be the underlying mechanism for
      the inhibitory effect. This is supported by the observation that inhibition is
      not seen at early time points, but requires prolonged IFN-gamma treatment. IFN
      gamma stimulation results in a loss of IL-4-induced Stat6 tyrosine
      phosphorylation, nuclear translocation, and DNA binding. Using the fibrosarcoma
      cell line U3A, which lacks Stat1, we demonstrated that the transcription
      activation function of Stat1 is required for the IFN-gamma-mediated repression.
      Repression was restored by overexpression of Stat1alpha, but not Stat1beta, in
      U3A cells. Treatment with IFN-gamma, but not IL-4, specifically up-regulates the
      expression of SOCS-1 (silencer of cytokine signaling), a recently characterized
      inhibitor of cytokine signaling pathways, such as IL-6 and IFN-gamma.
      Overexpression of SOCS-1 effectively blocks IL-4-induced Stat6 phosphorylation
      and transcription. This suggests that IFN-gamma-mediated repression of IL-4
      induced transcription is at least in part mediated by SOCS-1.

PMID- 10201929
TI  - Engagement of natural cytotoxicity programs regulates AP-1 expression in the NKL
      human NK cell line.
AB  - NK cell cytotoxicity is a fast and efficient mechanism of target cell lysis.
      Using transcription analysis, such as multiplex messenger assays, we show here
      that natural cytotoxicity exerted by the human NKL cell line correlates with mRNA
      accumulation of very early activator protein (AP)-1 transcription factor genes
      such as JunB, FosB and c-Fos. In addition, DNA-binding activities of Jun-Fos
      heterodimers were observed by electrophoretic mobility shift assays during the
      course of natural cytotoxicity. Interaction between immunoglobulin-like
      transcript-2/leukocyte Ig-like receptor 1 on NKL cells and HLA-B27 on target
      cells leads to an impairment of NKL natural cytotoxicity, which correlates with
      an absence of JunB, FosB, and c-Fos transcription, as well as an absence of their
      DNA-binding activity. Our studies thus indicate that, despite the rapidity of NK
      cell-mediated lysis, AP-1 transcription factor is activated during the early
      stage of NK cell cytolytic programs and that engagement of NK cell inhibitory
      receptors for MHC class I molecules impairs the very early activation of AP-1.

PMID- 10201930
TI  - Expression of murine IL-12 is regulated by translational control of the p35
      subunit.
AB  - IL-12 is a heterodimer of two subunits, p35 and p40, encoded by separate genes
      that are regulated independently. To investigate the mechanisms underlying the
      regulation of the p35 gene, we characterized murine p35 expression in the B cell
      lymphoma line A20 and in bone marrow-derived dendritic cells. Multiple
      transcription start sites were identified in both cell types, resulting in four
      p35 mRNA isoforms (types I-IV) that differ in the number and position of upstream
      ATGs in their 5' untranslated regions. In nonstimulated cells, the predominant
      forms of p35 message (types II and IV) contained an additional upstream ATG,
      whose presence was shown to inhibit the downstream translation of the p35
      subunit. After LPS stimulation, however, transcription initiated from alternate
      positions, so that the proportion of transcripts not containing this upstream ATG
      (types I and III) was significantly increased in the population of p35 mRNA.
      These type I and type III transcripts readily supported translation of the p35
      subunit and its incorporation into bioactive IL-12. Furthermore, p35 mRNA levels
      were substantially up-regulated after LPS stimulation in both cell types. Thus,
      our results show that p35 gene expression is highly regulated by both
      transcriptional and translational mechanisms.

PMID- 10201931
TI  - Scanning a DRB3*0101 (DR52a)-restricted epitope cross-presented by DR3:
      overlapping natural and artificial determinants in the human acetylcholine
      receptor.
AB  - A recurring epitope in the human acetylcholine receptor (AChR) alpha subunit
      (alpha146-160) is presented to specific T cells from myasthenia gravis patients
      by HLA-DRB3*0101-"DR52a"-or by DR4. Here we first map residues critical for DR52a
      in this epitope by serial Ala substitution. For two somewhat similar T cells,
      this confirms the recently deduced importance of hydrophobic "anchor" residues at
      peptide p1 and p9; also of Asp at p4, which complements this allele's distinctive
      Arg74 in DRbeta. Surprisingly, despite the 9 sequence differences in DRbeta
      between DR52a and DR3, merely reducing the bulk of the peptide's p1 anchor
      residue (Trp149-->Phe) allowed maximal cross-presentation to both T cells by DR3
      (which has Val86 instead of Gly). The shared K71G73R74N77 motif in the alpha
      helices of DR52a and DR3 thus outweighs the five differences in the floor of the
      peptide-binding groove. A second issue is that T cells selected in vitro with
      synthetic AChR peptides rarely respond to longer Ag preparations, whereas those
      raised with recombinant subunits consistently recognize epitopes processed
      naturally even from whole AChR. Here we compared one T cell of each kind, which
      both respond to many overlapping alpha140-160 region peptides (in proliferation
      assays). Even though both use Vbeta2 to recognize peptides bound to the same HLA
      DR52a in the same register, the peptide-selected line nevertheless proved to
      depend on a recurring synthetic artifact-a widely underestimated problem. Unlike
      these contaminant-responsive T cells, those that are truly specific for natural
      AChR epitopes appear less heterogeneous and therefore more suitable targets for
      selective immunotherapy.

PMID- 10201932
TI  - In vitro analysis of complement-dependent HIV-1 cell infection using a model
      system.
AB  - Previous studies based on the use of human serum as a source of C have provided
      evidence for the C-dependent enhancement of cell infection by HIV-1. The present
      study was undertaken to distinguish C from other serum factors and to identify
      the proteins and the mechanisms involved in C-dependent cell infection by HIV-1.
      The classical C activation pathway was reconstituted from the proteins C1q, C1r,
      C1s, C4, C2, C3, factor H, and factor I; each were purified to homogeneity. A
      mixture of these proteins at physiological concentrations was shown to reproduce
      the ability of normal human serum to enhance the infection of MT2 cells by HIV-1
      at low doses of virus. This enhancing effect was abolished when heat-inactivated
      serum and C2- or C3-depleted serum were used, and was restored upon addition of
      the corresponding purified proteins. A mixture of two synthetic peptides
      corresponding to positions 10-15 and 90-97 of human C receptor type 2 (CD21) as
      well as soluble CD4 both inhibited the C-dependent infection process. These data
      provide unambiguous evidence that HIV-1 triggers a direct activation of the
      classical C pathway in vitro and thereby facilitates the infection of MT2 cells
      at low doses of virus. These findings are consistent with a mechanism involving
      increased interaction between the virus opsonized by C3b-derived fragment(s) and
      the CD21 cell receptors and subsequent virus entry through CD4 receptors.

PMID- 10201933
TI  - Molecular cloning of a glycosylphosphatidylinositol-anchored molecule CDw108.
AB  - CDw108, also known as the John-Milton-Hagen human blood group Ag, is an 80-kDa
      glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein that is
      preferentially expressed on activated lymphocytes and E. The molecular
      characteristics and biological function of the CDw108 were not clarified
      previously. In this manuscript, we identify the cDNA clone containing the entire
      coding sequence of the CDw108 gene and report its molecular characteristics. The
      1998-base pairs of the open reading frame of the cloned cDNA encoded a protein of
      666 amino acids (aa), including the 46 aa of the signal peptide and the 19 aa of
      the GPI-anchor motif. Thus, the membrane-anchoring form of CDw108 was the 602 aa,
      and the estimated molecular mass of the unglycosylated form was 68 kDa. The RGD
      (Arg-Gly-Asp) cell attachment sequence and the five potential N-linked
      glycosylation sites were located on the membrane-anchoring form. Flow cytometric
      and immunoprecipitation analyses of the CDw108 cDNA transfectants confirmed that
      the cloned cDNA encoded the native form of CDw108. The CDw108 mRNA was expressed
      in activated PBMCs as well as in the spleen, thymus, testis, placenta, and brain,
      but was not expressed in any other tissues tested. Radiation hybrid mapping
      indicated that the CDw108 gene was located in the middle of the long arm of
      chromosome 15 (15q23-24). This molecular information will be critical for
      understanding the biological function of the CDw108 Ag.

PMID- 10201934
TI  - Endotoxin-mediated S-nitrosylation of p50 alters NF-kappa B-dependent gene
      transcription in ANA-1 murine macrophages.
AB  - Nitric oxide (NO) regulates cellular function, in part, by S-nitrosylating active
      site thiol groups of proteins. Ex vivo S-nitrosylation of NF-kappa B p50
      significantly decreases its capacity for DNA binding. To determine the cellular
      relevance of this observation, we utilized the ANA-l murine macrophage model of
      endotoxin (LPS)-mediated NO synthesis. In selected instances, the NO synthase
      inhibitor, L-arginine methyl ester (L-NAME; 100 microM), or the NO donor, S
      nitroso-N-acetylcysteine (SNAC; 100 microM), was added. In contrast to that of
      LPS cells, nuclear extracts from LPS + L-NAME cells demonstrated increased NF
      kappa B DNA binding on gel shift analysis. Addition of SNAC to LPS + L-NAME cells
      restored binding to a level equivalent to that of LPS cells. Spectrophotometric
      analysis of NF-kappa B p50 immunoprecipitates demonstrated S-NO bonds exclusively
      in LPS cells; these p50 protein isolates retained the same DNA binding
      characteristics as that of the nuclear extracts. Transfection assays utilizing NF
      kappa B-dependent promoter-reporter constructs demonstrated increased activity in
      LPS + L-NAME cells compared with LPS cells; nuclear run-on assays confirmed
      increased transcription of the corresponding genes. These results suggest that
      LPS-mediated NO synthesis is associated with S-nitrosylation of NF-kappa B p50
      and inhibition of NF-kappa B-dependent DNA binding, promoter activity, and gene
      transcription. We conclude that NO can regulate gene transcription by S
      nitrosylation of NF-kappa B.

PMID- 10201935
TI  - Structural requirements for CD43 function.
AB  - The regulation of T cell activation and adhesion by CD43 (leukosialin,
      sialophorin) has been thought to be mainly a function of the large size and
      negative charge of the extracellular domain of the protein. In this work, we
      demonstrate that the cytoplasmic tail is both necessary and sufficient for the
      negative regulatory effect of CD43 on cell-cell adhesion. Expression of mutant
      CD43 proteins in primary T cells from CD43-deficient mice demonstrated that the
      antiproliferative effect of CD43 is also dependent upon the cytoplasmic tail. In
      contrast, Ab-mediated costimulation through CD43 does not require the
      intracellular domain of CD43. These data demonstrate that CD43 primarily serves
      as a negative regulator of T cell activation and adhesion, and that this is
      mediated not exclusively by passive effects of the extracellular domain, but
      requires participation of the cytoplasmic tail, perhaps through interactions with
      the cytoskeleton, or alternatively, active regulation of intracellular signaling
      pathways.

PMID- 10201936
TI  - Cloning and modeling of the first nonmammalian CD4.
AB  - We have cloned and sequenced the first nonmammalian CD4 cDNA from the chicken
      using the COS cell expression method. Chicken CD4 contains four extracellular Ig
      domains that, in analogy to mammalian CD4, are in the order V, C2, V, and C2. The
      molecule is 24% identical with both human and mouse sequences. The extracellular
      domains were modeled using human and rat CD4 crystal structures as templates. In
      the first domain there are two extra Cys residues that are at suitable distance
      to form an intra-beta-sheet disulfide bridge in addition to the canonical one in
      the V domain. The region responsible for the interaction with MHC class II is
      relatively nonconserved in chicken. However, there are positively charged amino
      acids in the C" region of the N-terminal domain that may mediate the association
      to the negatively charged residues of the MHC class II beta-chain. Molecular
      modeling also implies that the membrane-proximal domain mediates dimerization of
      chicken CD4 in a similar way as it does for human CD4. Furthermore, the
      cytoplasmic tail is highly conserved, containing the protein tyrosine kinase
      p56lck recognition site that is preceded by an adjacent di-leucine motif for the
      internalization of the molecule. Interestingly, there are no Ser residues in the
      cytoplasmic part, which may explain the slow down-regulation of chicken CD4 after
      phorbol ester stimulation.

PMID- 10201937
TI  - Tolerization of mice to Schistosoma mansoni egg antigens causes elevated type 1
      and diminished type 2 cytokine responses and increased mortality in acute
      infection.
AB  - The granuloma that surrounds the Schistosoma mansoni egg is the cause of
      pathology in murine schistosomiasis, and its formation is driven by egg Ag
      stimulated type 1 and type 2 cytokines. To determine the role of egg-driven
      immune responses during schistosome infection we rendered CBA/Ca mice
      unresponsive to schistosome eggs by combined cyclophosphamide treatment and
      thymectomy. In the early acute stages of schistosome infection, egg-tolerized
      mice suffered high mortalities. Granuloma size and deposition of collagen in the
      liver were significantly reduced in egg-tolerized mice. Similarly, limited
      granuloma responses were detected in the intestines of these mice, and this was
      associated with a >90% reduction in egg excretion. Histologically, egg-tolerized
      mice had exacerbated hepatocyte damage, with extensive microvesicular steatosis.
      Elevated plasma transaminase levels confirmed the damage to hepatocytes. Infected
      egg-tolerized mice had impaired proliferation responses to egg Ag but intact
      responses to worm Ag. Tolerized mice had diminished Ab responses to egg Ag and
      had a type 1 cytokine isotype pattern to worm Ag, with elevated IgG2a and
      diminished IgG1 and IgE. Egg-tolerized mice failed to down-regulate type 1
      cytokines that are normally elicited during early schistosome infection. Hepatic
      granuloma cells from egg-tolerized mice were also type 1 cytokine dominated, with
      elevated frequencies of Tc1/Th1 and reduced Tc2/Th2 cells. This study
      demonstrates that mice tolerized to schistosome eggs have elevated type 1
      cytokine responses with diminished type 2 responses and reduced anti-egg Ab
      during schistosome infection, and these effects are detrimental to the host.

PMID- 10201938
TI  - B7-2 is required for the progression but not the initiation of the type 2 immune
      response to a gastrointestinal nematode parasite.
AB  - T cells require CD28/CTLA-4 costimulatory molecule interactions in addition to Ag
      specific signals through the TCR for in vivo effector Th cell function. Some
      studies have suggested that the ligands for these costimulatory molecules may
      differentially influence effector T cell function with B7-2 favoring a type 2
      response and B7-1 favoring a type 1 response, while other studies have suggested
      that these molecules may be redundant. The recent development of B7-2-deficient
      mice permits the direct analysis of the requirement of B7-2 during a type 2
      immune response to an infectious pathogen. We have examined, in B7-2-deficient
      mice, effector Th cell function and the associated type 2 immune response
      following infection with Heligmosomoides polygyrus, a natural murine parasitic
      nematode. Elevations in cytokine gene expression and protein secretion were
      pronounced and comparable in inoculated B7-2-/- and B7-2+/+ mice at day 8 after
      H. polygyrus inoculation. However, by day 14 after infection, increases in T cell
      cytokine expression were markedly inhibited in H. polygyrus-inoculated B7-2-/-
      mice. Furthermore, elevations in serum IgE and germinal center formation were
      inhibited at later stages of the immune response, while elevations in serum IgG1
      persisted. These findings suggest that certain T-dependent components vary in
      their B7-2-dependency during the type 2 immune response. They further demonstrate
      that B7-2 interactions are not necessary for the initiation of the type 2 immune
      response, but are instead required for its progression after the development of
      effector T cells.

PMID- 10201939
TI  - CD40 ligand-CD40 interaction induces chemokines in cervical carcinoma cells in
      synergism with IFN-gamma.
AB  - Cellular immunity plays a major role in controlling human papilloma virus
      infection and development of cervical carcinoma. Mononuclear cell infiltration
      possibly due to the action of chemokines becomes prominent in the tumor tissue.
      In fact, the macrophage chemoattractant protein-1, MCP-1, was detected in
      cervical squamous cell carcinoma in situ, whereas absent in cultured cells. From
      this, unknown environmental factors were postulated regulating chemokine
      expression in vivo. In this study, we show high CD40 expression on cervical
      carcinoma cells and CD40 ligand (CD40L) staining on attracted T cells in tumor
      tissue, suggesting a paracrine stimulation mechanism via CD40L-CD40 interactions.
      We therefore investigated chemokine synthesis in nonmalignant and malignant human
      papilloma virus-positive cell lines after CD40L exposure. Constitutive expression
      of MCP-1, MCP-3, RANTES, and IFN-gamma-inducible protein-10 was almost
      undetectable in all cell lines tested. CD40L was able to induce MCP-1 production;
      however, despite much higher CD40 expression in malignant cells, MCP-1 induction
      was significantly lower compared with nontumorigenic cells. After sensitization
      with IFN-gamma, another T cell-derived cytokine showing minimal effects on CD40
      expression levels, CD40 ligation led to a more than 20-fold MCP-1 induction in
      carcinoma cell lines. An even stronger effect was observed for IFN-gamma
      inducible protein-10. Our study highlights the synergism of T cell-derived
      mediators such as CD40L and IFN-gamma for chemokine responses in cervical
      carcinoma cells, helping to understand the chemokine expression patterns observed
      in vivo.

PMID- 10201940
TI  - Overexpression of Bcl-2 in transgenic mice decreases apoptosis and improves
      survival in sepsis.
AB  - In sepsis there is extensive apoptosis of lymphocytes, which may be beneficial by
      down-regulating the accompanying inflammation. Alternatively, apoptosis may be
      detrimental by impairing host defense. We studied whether Bcl-2, a potent
      antiapoptotic protein, could prevent lymphocyte apoptosis in a clinically
      relevant model of sepsis. Transgenic mice in which Bcl-2 was overexpressed in T
      cells had complete protection against sepsis-induced T lymphocyte apoptosis in
      thymus and spleen. Surprisingly, there was also a decrease in splenic B cell
      apoptosis in septic Bcl-2 overexpressors compared with septic HeJ and HeOuJ mice.
      There were marked increases in TNF-alpha, IL-1beta, and IL-10 in thymic tissue in
      sepsis in the three species of mice, and the increase in TNF-alpha and IL-10 in
      HeOuJ mice was greater than that in Bcl-2 mice. Mitotracker, a mitochondrial
      membrane potential indicator, demonstrated a sepsis-induced loss of membrane
      potential in T cells in HeJ and HeOuJ mice but not in Bcl-2 mice. Importantly,
      Bcl-2 overexpressors also had improved survival in sepsis. To investigate the
      potential impact of loss of lymphocytes on survival in sepsis, Rag-1-/- mice,
      which are totally deficient in mature T and B cells, were also studied. Rag-1-/-
      mice had decreased survival compared with immunologically normal mice with
      sepsis. We conclude that overexpression of Bcl-2 provides protection against cell
      death in sepsis. Lymphocyte death may be detrimental in sepsis by compromising
      host defense.

PMID- 10201941
TI  - Therapy of murine tumors with recombinant Bordetella pertussis adenylate cyclase
      carrying a cytotoxic T cell epitope.
AB  - Bordetella pertussis secretes an invasive adenylate cyclase toxin, CyaA, that is
      able to deliver its N-terminal catalytic domain into the cytosol of eukaryotic
      target cells directly through the cytoplasmic membrane. We have shown previously
      that recombinant CyaA can be used to deliver viral CD8+ T cell epitopes to the
      MHC-class I presentation pathway to trigger specific CTL responses in vivo. In
      the present study, we show that mice immunized with a detoxified but still
      invasive CyaA carrying a CD8+ T cell epitope of OVA developed strong epitope
      specific CTL responses, which kill tumor cells expressing this Ag. Treating mice
      with this recombinant molecule after the graft of melanoma cells expressing OVA
      induced a strong survival advantage compared with control animals. To our
      knowledge, this study represents the first demonstration that a nonreplicative
      and nontoxic vector carrying a single CTL epitope can stimulate efficient
      protective and therapeutic antitumor immunity.

PMID- 10201942
TI  - Dose dependence of CTL precursor frequency induced by a DNA vaccine and
      correlation with protective immunity against influenza virus challenge.
AB  - Intramuscular injection of BALB/c mice with a DNA plasmid encoding nucleoprotein
      (NP) from influenza virus A/PR/8/34 (H1N1) provides cross-strain protection
      against lethal challenge with influenza virus A/HK/68 (H3N2). CTL specific for
      the H-2Kd-restricted epitope NP147-155 are present in these mice and are thought
      to play a role in the protection. To assess the effectiveness of NP DNA
      immunization in comparison with influenza virus infection in the induction of CTL
      responses, we monitored the frequency of CTL precursors (CTLp) in mice following
      i.m. injection with NP DNA or intranasal infection with influenza virus and
      showed that the CTLp frequency in NP DNA-immunized mice can reach levels found in
      mice that had been infected with influenza virus. We also measured the CTLp
      frequency, anti-NP Ab titers, and T cell proliferative responses in mice that
      were injected with titrated dosages of NP DNA and documented a correlation of the
      CTLp frequency and the Ab titers, but not proliferative responses, with the
      injection dose. Furthermore, we observed a positive correlation between the
      frequency of NP147-155 epitope-specific CTLp and the extent of protective
      immunity against cross-strain influenza challenge induced by NP DNA injection.
      Collectively, these results and our early observations from adoptive transfer
      experiments of in vitro activated lymphocytes from NP DNA-immunized mice suggest
      a protective function of NP-specific CTLp in mice against cross-strain influenza
      virus challenge.

PMID- 10201943
TI  - Induction and regulation of macrophage metalloelastase by hyaluronan fragments in
      mouse macrophages.
AB  - Although the metalloproteinase murine metalloelastase (MME) has been implicated
      in lung disorders such as emphysema and pulmonary fibrosis, the mechanisms
      regulating MME expression are unclear. Low m.w. fragments of the extracellular
      matrix component hyaluronan (HA) that accumulate at sites of lung inflammation
      are capable of inducing inflammatory gene expression in macrophages (Mphi). The
      purpose of this study was to examine the effect of HA fragments on the expression
      of MME in alveolar Mphi. The mouse alveolar Mphi cell line MH-S was stimulated
      with HA fragments over time, total RNA was isolated, and Northern blot analysis
      was performed. HA fragments induced MME mRNA in a time-dependent fashion, with
      maximal levels at 6 h. HA fragments also induced MME protein expression as well
      as enzyme activity. The induction of MME gene expression was specific for low
      m.w. HA fragments and dependent upon new protein synthesis; it occurred at the
      level of gene transcription. We also examined the effect of HA fragments on MME
      expression in inflammatory alveolar Mphi from bleomycin-injured rat lungs.
      Although normal rat alveolar Mphi did not express MME mRNA in response to HA
      fragments, alveolar Mphi from the bleomycin-treated rats responded to HA fragment
      stimulation by increasing MME mRNA levels. Furthermore, baseline and HA fragment
      induced MME gene expression in alveolar Mphi from bleomycin-treated rats was
      inhibited by IFN-gamma. These data suggest that HA fragments may be an important
      mechanism for the expression of MME by Mphi in inflammatory lung disorders.

PMID- 10201944
TI  - Mutations in immunodominant T cell epitopes derived from the nonstructural 3
      protein of hepatitis C virus have the potential for generating escape variants
      that may have important consequences for T cell recognition.
AB  - One of the most disturbing features of hepatitis C virus (HCV) is its long-term
      persistence in the host. One hypothesis to explain this phenomenon is that HCV
      escapes immune recognition through its intrinsic hypermutability. To determine
      whether immunodominant T cell epitopes derived from HCV nonstructural 3 (NS3)
      protein might be subject to sequence variations leading to escape mutants, we
      examined sequence variations of one IL-2-producing epitope, NS3358-375, and one
      IL-10-producing epitope, NS3505-521. By PCR amplification, cloning, and
      sequencing, we observed significant sequence variations in the two epitopes,
      although the selection intensity for each epitope was different. For NS3358-375,
      more variants were observed, and for NS3505-521, fewer mutations were observed.
      Moreover, functional studies revealed that three NS3358-375 and one NS3505-521
      variants failed to stimulate T cell proliferation, and two other NS3358-375 and
      NS3505-521 variants weakly stimulated T cell responses. Our results are
      consistent with immune selection of viral variants at the epitope level, which
      may enable HCV to evade host defenses over time.

PMID- 10201945
TI  - Ectopic expression of DNA encoding IFN-alpha 1 in the cornea protects mice from
      herpes simplex virus type 1-induced encephalitis.
AB  - A novel approach to combat acute herpes simplex virus type 1 (HSV-1) infection
      has recently been developed by administration with a plasmid DNA construct
      encoding cytokine genes. Cytokines, especially type I IFNs (IFN-alpha and IFN
      beta) play an important role in controlling acute HSV-1 infection. The purpose of
      the present study was to investigate the potential efficacy of ectopically
      expressed IFN-alpha 1 against ocular HSV-1 infection following in situ
      transfection of mouse cornea with a naked IFN-alpha 1-containing plasmid DNA.
      Topical administration of the IFN-alpha 1 plasmid DNA exerted protection against
      ocular HSV-1 challenge in a time- and dose-dependent manner and antagonized HSV-1
      reactivation. In addition, IFN-alpha 1-transfected eyes expressed a fivefold
      increase in MHC class I mRNA over vector-treated controls. The protective
      efficacy of the IFN-alpha 1 transgene antagonized viral replication, as evidenced
      by the reduction of the viral gene transcripts (infected cell polypeptide 27,
      thymidine kinase, and viral protein 16) and viral load in eyes and trigeminal
      ganglia during acute infection. The administration of neutralizing Ab to IFN
      alpha beta antagonized the protective effect of the IFN-alpha 1 transgene in
      mice. Collectively, these findings demonstrate the potential of using naked
      plasmid DNA transfection in the eye to achieve ectopic gene expression of
      therapeutically active agents.

PMID- 10201946
TI  - Regulation of cytosolic COX-2 and prostaglandin E2 production by nitric oxide in
      activated murine macrophages.
AB  - Murine macrophages (RAW 264.7) when stimulated with LPS show 90% distribution of
      cyclooxygenase-2 (COX-2) in the nuclear fraction and approximately 10% in the
      cytosolic fraction. Further analysis of this cytosolic fraction at 100,000 x g
      indicates that the COX-2 is distributed both in the 100,000 x g soluble fraction
      and membrane fraction. Stimulation of RAW 264.7 cells with LPS in the presence of
      inducible nitric oxide synthase inhibitor L-NMMA at concentrations that inhibit
      nitrite accumulation by </=80% is inadequate to augment PGE2 production. However,
      inhibition of nitrite accumulation by >/=85% with higher concentrations of L-NMMA
      shows 1) up-regulation of PGE2 production, 2) accumulation of COX-2 protein in
      the 100,000 x g soluble and membrane fractions of the cytosolic fraction, and 3)
      with no significant effects on the accumulation of COX-2 mRNA. These experiments
      suggest that low concentrations of nitric oxide (10-15% of the total) attenuate
      PGE2 production in response to LPS in RAW 264.7 cells. This inhibition is, in
      part, due to decreased expression of cytosolic COX-2 protein.

PMID- 10201948
TI  - CD8 T cells are essential in the development of respiratory syncytial virus
      induced lung eosinophilia and airway hyperresponsiveness.
AB  - Viral respiratory infections can cause bronchial hyperresponsiveness and
      exacerbate asthma. In mice, respiratory syncytial virus (RSV) infection results
      in airway hyperresponsiveness (AHR) and eosinophil influx into the airways. The
      immune cell requirements for these responses to RSV infection are not well
      defined. To delineate the role of CD8 T cells in the development of RSV-induced
      AHR and lung eosinophilia, we tested the ability of mice depleted of CD8 T cells
      to develop these symptoms of RSV infection. BALB/c mice were depleted of CD8 T
      cells using anti-CD8 Ab treatment before intranasal administration of infectious
      RSV. Six days postinfection, airway responsiveness to inhaled methacholine was
      assessed by barometric body plethysmography, and numbers of lung eosinophils and
      levels of IFN-gamma, IL-4, and IL-5 in bronchoalveolar lavage fluid were
      monitored. RSV infection resulted in airway eosinophilia and AHR in control mice,
      but not in CD8-depleted animals. Further, whereas RSV-infected mice secreted
      increased amounts of IL-5 into the airways as compared with noninfected controls,
      no IL-5 was detectable in both bronchoalveolar lavage fluid and culture
      supernatants from CD8-depleted animals. Treatment of CD8-depleted mice with IL-5
      fully restored both lung eosinophilia and AHR. We conclude that CD8 T cells are
      essential for the influx of eosinophils into the lung and the development of AHR
      in response to RSV infection.

PMID- 10201947
TI  - Extracellular signal-regulated kinases regulate leukotriene C4 generation, but
      not histamine release or IL-4 production from human basophils.
AB  - Human basophils secrete histamine and leukotriene C4 (LTC4) in response to
      various stimuli, such as Ag and the bacterial product, FMLP. IgE-mediated
      stimulation also results in IL-4 secretion. However, the mechanisms of these
      three classes of secretion are unknown in human basophils. The activation of
      extracellular signal-regulated kinases (ERKs; ERK-1 and ERK-2) during IgE- and
      FMLP-mediated stimulation of human basophils was examined. Following FMLP
      stimulation, histamine release preceded phosphorylation of ERKs, whereas
      phosphorylation of cytosolic phospholipase A2 (cPLA2), and arachidonic acid (AA)
      and LTC4 release followed phosphorylation of ERKs. The phosphorylation of ERKs
      was transient, decreasing to baseline levels after 15 min. PD98059 (MEK
      inhibitor) inhibited the phosphorylation of ERKs and cPLA2 without inhibition of
      several other tyrosine phosphorylation events, including phosphorylation of p38
      MAPK. PD98059 also inhibited LTC4 generation (IC50 = approximately 2 microM), but
      not histamine release. Stimulation with anti-IgE Ab resulted in the
      phosphorylation of ERKs, which was kinetically similar to both histamine and LTC4
      release and decreased toward resting levels by 30 min. Similar to FMLP, PD98059
      inhibited anti-IgE-mediated LTC4 release (IC50, approximately 2 microM), with
      only a modest effect on histamine release and IL-4 production at higher
      concentrations. Taken together, these results suggest that ERKs might selectively
      regulate the pathway leading to LTC4 generation by phosphorylating cPLA2, but not
      histamine release or IL-4 production, in human basophils.

PMID- 10201949
TI  - Inhibition of matrix metalloproteinases prevents allergen-induced airway
      inflammation in a murine model of asthma.
AB  - Although matrix metalloproteinases (MMPs) have been reported to play crucial
      roles in the migration of inflammatory cells through basement membrane components
      in vitro, the role of MMPs in the in vivo accumulation of the cells to the site
      of inflammation in bronchial asthma is still obscure. In this study, we
      investigated the role of MMPs in the pathogenesis of bronchial asthma, using a
      murine model of allergic asthma. In this model, we observed the increase of the
      release of MMP-2 and MMP-9 in bronchoalveolar lavage fluids after Ag inhalation
      in the mice sensitized with OVA, which was accompanied by the infiltration of
      lymphocytes and eosinophils. Administration of tissue inhibitor of
      metalloproteinase-2 to airways inhibited the Ag-induced infiltration of
      lymphocytes and eosinophils to airway wall and lumen, reduced Ag-induced airway
      hyperresponsiveness, and increased the numbers of eosinophils and lymphocytes in
      peripheral blood. The inhibition of cellular infiltration to airway lumen was
      observed also with tissue inhibitor of metalloproteinase-1 and a synthetic matrix
      metalloproteinase inhibitor. These data suggest that MMPs, especially MMP-2 and
      MMP-9, are crucial for the infiltration of inflammatory cells and the induction
      of airway hyperresponsiveness, which are pathophysiologic features of bronchial
      asthma, and further raise the possibility of the inhibition of MMPs as a
      therapeutic strategy of bronchial asthma.

PMID- 10201950
TI  - Lipopolysaccharide-coated erythrocytes activate human neutrophils via CD14 while
      subsequent binding is through CD11b/CD18.
AB  - Interaction of LPS with monocytes and neutrophils is known to occur via CD14 and
      is strongly enhanced by LPS-binding protein (LBP). Integrins as well as CD14 play
      a role in the interaction of erythrocytes (E) coated with LPS or whole Gram
      negative bacteria with phagocytes. We reasoned that the density of LPS on a
      particle is an important determinant in these interactions. Therefore, E were
      coated with different concentrations of LPS (ELPS). The binding of these ELPS to
      neutrophils was evaluated by flow cytometry. Simultaneously, we measured fMLP
      receptor expression to evaluate neutrophil activation. ELPS only bound to
      neutrophils in the presence of LBP. Blocking CD14 inhibited both activation and
      binding, whereas blocking complement (C) receptor 3 (CR3) inhibited binding but
      not activation. TNF activation restored ELPS binding in CD14-blocked cells but
      not in cells in which CR3 was blocked. Salmonella minnesota did bind to
      neutrophils independent of CR3 or CD14. The addition of LBP enhanced binding
      twofold, and this surplus was dependent upon CD14 but not on CR3. We conclude
      that ELPS interact with neutrophils via CD14, initially giving rise to cell
      activation; subsequently, binding is solely mediated by activated CR3.

PMID- 10201951
TI  - Nuclear factor-kappa B mediates TNF-alpha inhibitory effect on alpha 2(I)
      collagen (COL1A2) gene transcription in human dermal fibroblasts.
AB  - Among its plethora of activities as an inflammatory mediator, TNF-alpha has
      potent regulatory control on extracellular matrix production and degradation.
      Earlier studies have documented that TNF-alpha inhibits type I collagen gene
      (COL1A2) expression at the transcriptional level, but the characterization of the
      transcription factors involved has been elusive. In the present study, using
      transient cell transfection of human dermal fibroblasts with a battery of 5' end
      deletion/chloramphenicol acetyltransferase (CAT) reporter gene constructs, we
      have characterized the TNF-alpha response element of the COL1A2 promoter. The TNF
      alpha response element was attributed to a specific region that comprises
      noncanonical activator protein-1 (AP-1) (CGAGTCA) and NF-kappa B (AGAGTTTCCC)
      binding sites. TNF-alpha effect was eliminated by a 2-bp substitution mutation in
      the NF-kappa B1 binding half site of the NF-kappa B cis element. Electrophoretic
      mobility shift assays (EMSA) showed that recombinant human NF-kappa B
      heterodimers as well as NF-kappa B1 and RelA homodimers, but not AP-1, were
      capable of binding this element. Further, EMSA with human fibroblast nuclear
      extracts demonstrated enhanced binding of a single, specific complex within 5 min
      of TNF-alpha stimulation, which reached a plateau by 1 h and was not affected by
      preincubation of cells with cycloheximide. Gel supershift assays identified the
      complex as the NF-kappa B (p50/p65) heterodimer, whereas Abs to nuclear factor of
      activated T cells (NF-AT) and Jun family members failed to recognize the complex.
      These data suggest that in fibroblasts TNF-alpha activates and initiates the
      nuclear translocation of NF-kappa B that binds a divergent NF-kappa B element and
      plays a critical role in the observed inhibition of alpha 2(I) collagen gene
      transcription.

PMID- 10201952
TI  - TNF-alpha regulates corneal Langerhans cell migration.
AB  - Langerhans cells (LC) belong to the dendritic cell family and mediate Ag
      presentation in the cornea and ocular surface. Under normal physiological
      conditions, the central cornea is devoid of LC. Centripetal migration of LC plays
      a critical role in promoting immunoinflammatory responses in the eye including
      allograft rejection and herpetic keratitis. The molecular mechanisms responsible
      for ocular LC migration are poorly understood. To examine whether TNF-alpha
      mediates corneal LC migration and to establish the interaction of IL-1 and TNF
      alpha in regulating LC migratory capacity, we utilized gene-targeted knockout
      mice lacking IL-1 receptor I (IL-1RI-/-), TNF receptor I (p55-/-), TNF receptor
      II (p75-/-), or both (p55-/-p75-/-). LC migration was induced by thermal cautery
      or cytokine injection and enumerated by an immunofluorescence assay. Migration of
      LC after cauterization and TNF-alpha injection was significantly depressed in
      both p55-/- and p75-/- mice. Similarly, in the first 72 h after intracorneal
      injection of IL-1alpha, LC migration was reduced in p55-/-, p75-/-, and p55-/-p75
      /- mice. In contrast, injection of TNF-alpha in IL-1RI-/- mice led to normal
      migration of corneal LC indistinguishable from wild-type controls. These results
      suggest that the IL-1 induction of corneal LC migration is largely mediated by
      TNFR function, whereas TNF-alpha induction of LC migration is independent of IL
      1RI activity. Moreover, the data suggest that both p55 and p75 signaling pathways
      are important in mediating LC migration in the cornea.

PMID- 10201953
TI  - Endocytosis of heparin-binding protein (CAP37) is essential for the enhancement
      of lipopolysaccharide-induced TNF-alpha production in human monocytes.
AB  - Heparin-binding protein (HBP), also known as CAP37, is a proteolytically inactive
      serine protease homologue that is released from activated granulocytes. However,
      HBP is not a biologically inactive molecule but rather a multifunctional protein
      with properties that include the enhancement of LPS-induced TNF-alpha production
      from monocytes. We have previously demonstrated that HBP is internalized in
      monocytes. In the current study, we hypothesize that HBP is internalized in
      monocytes via endocytosis, and this internalization is an important mechanism by
      which HBP enhances LPS-induced TNF-alpha release. Using whole blood from healthy
      donors and flow cytometry, we found that colchicine (0.1-10 mM), cytochalasin D
      (1000 microM), NH4Cl (10-50 mM), and bafilomycin A1 (0.1-3 microM) significantly
      reduced the affinity of FITC-HBP for CD14-positive monocytes. Using isolated
      human monocytes and ELISA, we found that colchicine (0.1 mM), cytochalasin D (30
      and 300 microM), NH4Cl (30 mM), and bafilomycin A1 (1 microM) significantly
      reduced the effect of HBP (10 microg/ml) to enhance LPS (10 ng/ml)-induced TNF
      alpha release after 24 h. These findings demonstrate that internalization of HBP
      in monocytes is essential for the enhancement of LPS-induced TNF-alpha release.
      Transport of HBP to an activating compartment depends on intact F-actin
      polymerization and endosomal acidification, an important mechanism for endosomal
      protein sorting and trafficking.

PMID- 10201954
TI  - Differential expression and activation of p38 mitogen-activated protein kinase
      alpha, beta, gamma, and delta in inflammatory cell lineages.
AB  - Four p38 mitogen-activated protein kinases (p38alpha, beta, gamma, delta) have
      been described. To understand the role of p38 family members in inflammation, we
      determined their relative expression in cells that participate in the
      inflammatory process. Expression was measured at the level of mRNA by reverse
      transcriptase PCR and protein by Western blot analysis. p38alpha was the dominant
      form of p38 in monocytes; expression of p38delta was low and p38beta was
      undetected. In macrophages, p38alpha and p38delta were abundant, but p38beta was
      undetected. p38alpha and p38delta were also expressed by neutrophils, CD4+ T
      cells, and endothelial cells. Again, p38beta was not detected in neutrophils,
      although low amounts were present in CD4+ T cells. In contrast, p38beta was
      abundant in endothelial cells. p38gamma protein was not detected in any cell
      type, although p38gamma mRNA was present in endothelial cells. Immunokinase
      assays showed a strong activation of p38alpha and a lesser activation of p38delta
      in LPS-stimulated macrophages. Abs specific for mono- and dual-phophorylated
      forms of p38 suggested that LPS induces dual phosphorylation of p38alpha, but
      primarily mono-phosphorylation of p38delta. IL-1beta activated p38alpha and
      p38beta in endothelial cells. However, p38alpha was the more activated form based
      on kinase assays and phosphorylation analysis. Expression and activation patterns
      of p38alpha in macrophages and endothelial cells suggest that p38alpha plays a
      major role in the inflammatory response. Additional studies will be needed to
      define the contribution of p38delta to macrophage, neutrophil, and T cell
      functions, and of p38beta to signaling in endothelial cells and T cells.

PMID- 10201955
TI  - Ligation of Fc gamma RII (CD32) pivotally regulates survival of human
      eosinophils.
AB  - The low-affinity IgG Fc receptor, FcgammaRII (CD32), mediates various effector
      functions of lymphoid and myeloid cells and is the major IgG Fc receptor
      expressed by human eosinophils. We investigated whether FcgammaRII regulates both
      cell survival and death of human eosinophils. When cultured in vitro without
      growth factors, most eosinophils undergo apoptosis within 96 h. Ligation of
      FcgammaRII by anti-CD32 mAb in solution inhibited eosinophil apoptosis and
      prolonged survival in the absence of growth factors. Cross-linking of human IgG
      bound to FcgammaRII by anti-human IgG Ab or of unoccupied FcgammaRII by
      aggregated human IgG also prolonged eosinophil survival. The enhanced survival
      with anti-CD32 mAb was inhibited by anti-granulocyte-macrophage-CSF (GM-CSF) mAb,
      suggesting that autocrine production of GM-CSF by eosinophils mediated survival.
      In fact, mRNA for GM-CSF was detected in eosinophils cultured with anti-CD32 mAb.
      In contrast to mAb or ligands in solution, anti-CD32 mAb or human IgG, when
      immobilized onto tissue culture plates, facilitated eosinophil cell death even in
      the presence of IL-5. Cell death induced by these immobilized ligands was
      accompanied by DNA fragmentation and was inhibited when eosinophil beta2 integrin
      was blocked by anti-CD18 mAb, suggesting that beta2 integrins play a key role in
      initiating eosinophil apoptosis. Thus, FcgammaRII may pivotally regulate both
      survival and death of eosinophils, depending on the manner of receptor ligation
      and beta2 integrin involvement. Moreover, the FcgammaRII could provide a novel
      mechanism to control the number of eosinophils at inflammation sites in human
      diseases.

PMID- 10201956
TI  - Augmentation of type I IL-1 receptor expression and IL-1 signaling by IL-6 and
      glucocorticoid in murine hepatocytes.
AB  - IL-1 signal is transduced through type I receptor (IL-1RI). We have recently
      reported that LPS augments IL-1RI mRNA expression in the hepatocytes of mice in
      vivo, and the augmentation is mediated by the interaction of IL-1, IL-6, and
      glucocorticoid (GC). In this study, we examined whether IL-1RI mRNA expression
      level in the hepatocytes reflects those of cell surface molecule and IL-1
      signaling. When primary cultured murine hepatocytes were treated with
      dexamethasone (Dex) or IL-6, these two reagents synergistically up-regulated IL
      1RI mRNA expression in the cells. 125I-labeled IL-1 binding experiment showed
      that the level of binding was also up-regulated by the treatment with Dex and IL
      6. Scatchard analysis revealed that the number of IL-1R increased. The increased
      binding of IL-1 was completely inhibited by an Ab against murine IL-1RI,
      indicating that Dex and IL-6 augmented the expression of cell surface IL-1RI
      molecule. When hepatocytes were pretreated with Dex and IL-6, the activation of
      IL-1R-associated kinase was augmented in response to IL-1, indicating that IL-1
      signaling was also augmented. In addition, IL-1 treatment following
      administration of the combination of Dex and IL-6 into mice markedly increased
      the serum level of serum amyloid A. These results indicate that GC and IL-6
      augment the expression of cell surface IL-1RI in hepatocytes, as well as IL-1
      signaling and IL-1R-associated kinase activation, through up-regulation of IL-1RI
      mRNA level, which represents a novel regulatory network between IL-1, GC, and IL
      6.

PMID- 10201957
TI  - Importance of CD23 for collagen-induced arthritis: delayed onset and reduced
      severity in CD23-deficient mice.
AB  - Increased expression of the low affinity receptor for IgE, FcepsilonRII/CD23 has
      been observed in rheumatoid arthritis. In view of this, we have investigated the
      expression and influence of CD23 in collagen-induced arthritis (CIA), an animal
      model for rheumatoid arthritis. CD23+ cells were analyzed in lymph nodes of DBA/1
      mice immunized with bovine collagen type II (BCII) in CFA or with CFA only. The
      percentage of CD23+ lymph node cells was increased in both BCII/CFA- and CFA
      immunized mice at 1, 3, and 7 wk after immunization compared with unimmunized
      mice, indicating a role for the adjuvant to trigger general inflammation and CD23
      expression. To investigate the functional role of CD23 in CIA, CD23-deficient
      mice on the DBA/1 genetic background were studied. After immunization with
      BCII/CFA, these mice developed CIA with delayed onset and reduced severity
      compared with wild-type mice. These findings suggest that an increased number of
      CD23+ cells is part of an inflammatory response and that CD23 expression is of
      pathogenic importance in the arthritic process.

PMID- 10201958
TI  - Nerve growth factor modifies the expression of inflammatory cytokines by mast
      cells via a prostanoid-dependent mechanism.
AB  - Nerve growth factor (NGF) is well recognized to have a number of potent effects
      on mast cells, including increasing mast cell numbers in vivo and inducing mast
      cell degranulation in vitro. More recently, NGF has been demonstrated to induce
      PGD2 production by mast cells through the induction of mast cell cyclooxygenase
      expression. We have observed that NGF at doses as low as 10 ng/ml will induce IL
      6 production and inhibit TNF-alpha release from rat peritoneal mast cells in the
      presence of lysophosphatidylserine as a cofactor. NGF synergizes with LPS
      treatment of peritoneal mast cells (PMC) for the induction of IL-6. Examination
      of the mechanism of this phenomenon has revealed that NGF can induce both rat PMC
      and mouse bone marrow-derived cultured mast cells to produce substantial levels
      of PGE2. This response is maximal at later time points 18-24 h after NGF
      activation. The ability of NGF to induce PGE2 is not dependent on mast cell
      degranulation. Other stimuli capable of inducing IL-6, such as LPS, do not induce
      production of this prostanoid. Inhibition of cyclooxygenase activity by PMC using
      either flurbiprofen or indomethacin inhibited both the NGF-induced PGE2 synthesis
      and the NGF-induced alterations in TNF-alpha and IL-6 production. These results
      suggest a role for mast cell-derived prostanoids in the regulation of local
      inflammatory responses and neuronal degeneration after tissue injury involving
      induction of NGF production.

PMID- 10201959
TI  - A novel glycosylphosphatidyl inositol-anchored protein on human leukocytes: a
      possible role for regulation of neutrophil adherence and migration.
AB  - We report here a novel glycosylphosphatidyl-inositol (GPI)-anchored glycoprotein
      on human leukocytes. Treatment of neutrophils with a mAb (3H9) to this molecule
      sequentially up-regulates and down-regulates beta2 integrin-dependent adhesion of
      these cells as well as their transendothelial migration in vitro. In addition,
      this mAb simultaneously modulates the avidity of beta2 integrin for its ligand,
      iC3b, with kinetics similar to those observed in 3H9 modulation of neutrophil
      adherence. This mAb also induces beta2 integrin-dependent cytoskeletal
      remodeling. This novel GPI-anchored protein (GPI-80) is highly homologous with
      Vanin-1, a recently reported GPI-anchored protein that is expressed on
      perivascular thymic stromal cells and is involved in thymus homing in mice. The
      finding that both GPI-80 and Vanin-1 are 40% homologous with human biotinidase
      suggests the existence of a biotinidase superfamily of molecules that may be
      involved in the regulation of leukocyte trafficking.

PMID- 10201960
TI  - Eotaxin activates T cells to chemotaxis and adhesion only if induced to express
      CCR3 by IL-2 together with IL-4.
AB  - The transmigration and adherence of T lymphocytes through microvascular
      endothelium are essential events for their recruitment into inflammatory sites.
      In the present study, we investigated the expression of CC chemokine receptor
      CCR3 on T lymphocytes and the capacities of the CC chemokine eotaxin to induce
      chemotaxis and adhesion in T lymphocytes. We have observed a novel phenomenon
      that IL-2 and IL-4 induce the expression of CCR3 on T lymphocytes. We also report
      that CC chemokine eotaxin is a potent chemoattractant for IL-2- and IL-4
      stimulated T lymphocytes, but not for freshly isolated T lymphocytes. Eotaxin
      attracts T lymphocytes via CCR3, documented by the fact that anti-CCR3 mAb blocks
      eotaxin-mediated T lymphocyte chemotaxis. In combination with IL-2 and IL-4,
      eotaxin enhances the expression of adhesion molecules such as ICAM-1 and several
      integrins (CD29, CD49a, and CD49b) on T lymphocytes and thus promotes adhesion
      and aggregation of T lymphocytes. The eotaxin-induced T lymphocyte adhesion could
      be selectively blocked by a specific cAMP-dependent protein kinase inhibitor, H
      89, indicating that eotaxin activates T lymphocytes via a special cAMP-signaling
      pathway. Our new findings all point toward the fact that eotaxin, in association
      with the Th1-derived cytokine IL-2 and the Th2-derived cytokine IL-4, is an
      important T lymphocyte activator, stimulating the directional migration,
      adhesion, accumulation, and recruitment of T lymphocytes, and paralleled the
      accumulation of eosinophils and basophils during the process of certain types of
      inflammation such as allergy.

PMID- 10201961
TI  - IL-16 as an anti-inflammatory cytokine in rheumatoid synovitis.
AB  - T lymphocytes are a major component of the inflammatory infiltrate in rheumatoid
      synovitis, but their exact role in the disease process is not understood.
      Functional activities of synovial T cells were examined by adoptive transfer
      experiments in human synovium-SCID mouse chimeras. Adoptive transfer of tissue
      derived autologous CD8+ T cells induced a marked reduction in the activity of
      lesional T cells and macrophages. Injection of CD8+, but not CD4+, T cells
      decreased the production of tissue IFN-gamma, IL-1beta, and TNF-alpha by >90%.
      The down-regulatory effect of adoptively transferred CD8+ T cells was not
      associated with depletion of synovial CD3+ T cells or synovial CD68+ macrophages,
      and it could be blocked by Abs against IL-16, a CD8+ T cell-derived cytokine. In
      the synovial tissue, CD8+ T cells were the major source of IL-16, a natural
      ligand of the CD4 molecule that can anergize CD4-expressing cells. The anti
      inflammatory activity of IL-16 in rheumatoid synovitis was confirmed by treating
      synovium-SCID mouse chimeras with IL-16. Therapy for 14 days with recombinant
      human IL-16 significantly inhibited the production of IFN-gamma, IL-1beta, and
      TNF-alpha in the synovium. We propose that tissue-infiltrating CD8+ T cells in
      rheumatoid synovitis have anti-inflammatory activity that is at least partially
      mediated by the release of IL-16. Spontaneous production of IL-16 in synovial
      lesions impairs the functional activity of CD4+ T cells but is insufficient to
      completely abrogate their stimulation. Supplemental therapy with IL-16 may be a
      novel and effective treatment for rheumatoid arthritis.

PMID- 10201962
TI  - Golli-induced paralysis: a study in anergy and disease.
AB  - The Golli-MBP transcription unit contains three Golli-specific exons as well as
      the seven exons of the classical myelin basic protein (MBP) gene and encodes
      alternatively spliced proteins that share amino acid sequence with MBP. Unlike
      MBP, which is a late Ag expressed only in the nervous system, Golli exon
      containing gene products are expressed both pre- and postnatally at many sites,
      including lymphoid tissue, as well as in the central nervous system. To
      investigate whether Golli-MBP peptides unique to Golli would result in
      neurological disease, we immunized rats and observed a novel neurological disease
      characterized by mild paralysis and the presence of groups of lymphocytes in the
      subarachnoid space but not in the parenchyma of the brain. Disease was induced by
      Th1-type T cells that displayed an unusual activation phenotype. Primary
      stimulation in vitro induced T cell proliferation with increased surface CD45RC
      that did not become down-regulated as it did in other Ag-stimulated cultures.
      Secondary stimulation of this CD45RChigh population with Ag, however, did not
      induce proliferation or IL-2 production, although an IFN-gamma-producing
      population resulted. Proliferation could be induced by secondary stimulation with
      IL-2 or PMA-ionomycin, suggesting an anergic T cell population. Cells could
      adoptively transfer disease after secondary stimulation with IL-2, but not with
      Ag alone. These responses are suggestive of a chronically stimulated, anergic
      population that can be transiently activated to cause disease, fall back into an
      anergic state, and reactivated to cause disease again. Such a scenario may be
      important in chronic human disease.

PMID- 10201963
TI  - The role of the human Fc receptor Fc gamma RIIA in the immune clearance of
      platelets: a transgenic mouse model.
AB  - In humans, the Fc receptor for IgG, FcgammaRIIA, is expressed on macrophages and
      platelets and may play an important role in the pathophysiology of immune
      mediated thrombocytopenia. Mice lack the genetic equivalent of human FcgammaRIIA.
      To better understand the role of FcgammaRIIA in vivo, FcgammaRIIA transgenic mice
      were generated and characterized. One transgenic mouse line expressed FcgammaRIIA
      on platelets and macrophages at levels equivalent to human cells, and cross
      linking FcgammaRIIA on these platelets induced platelet aggregation. Immune
      mediated thrombocytopenia in this transgenic line was studied using i.v. and i.p.
      administration of anti-mouse platelet Ab. In comparison with matched wild-type
      littermates that are negative for the FcgammaRIIA transgene, Ab-mediated
      thrombocytopenia was significantly more severe in the FcgammaRIIA transgenic
      mice. In contrast, FcR gamma-chain knockout mice that lack functional expression
      of the Fc receptors FcgammaRI and FcgammaRIII on splenic macrophages did not
      demonstrate Ab-mediated thrombocytopenia. We generated FcgammaRIIA transgenic x
      FcR gamma-chain knockout mice to examine the role of FcgammaRIIA in immune
      clearance in the absence of functional FcgammaRI and FcgammaRIII. In FcgammaRIIA
      transgenic x FcR gamma-chain knockout mice, severe immune thrombocytopenia
      mediated by FcgammaRIIA was observed. These results demonstrate that FcgammaRIIA
      does not require the FcR gamma-chain for expression or function in vivo.
      Furthermore, taken together, the data suggest that the human Fc receptor
      FcgammaRIIA plays a significant role in the immune clearance of platelets in
      vivo.

PMID- 10201964
TI  - Increased peroxynitrite activity in AIDS dementia complex: implications for the
      neuropathogenesis of HIV-1 infection.
AB  - Oxidative stress is suggested to be involved in several neurodegenerative
      diseases. One mechanism of oxidative damage is mediated by peroxynitrite, a
      neurotoxic reaction product of superoxide anion and nitric oxide. Expression of
      two cytokines and two key enzymes that are indicative of the presence of reactive
      oxygen intermediates and peroxynitrite was investigated in brain tissue of AIDS
      patients with and without AIDS dementia complex and HIV-seronegative controls.
      RNA expression of IL-1beta, IL-10, inducible nitric oxide synthase, and
      superoxide dismutase (SOD) was found to be significantly higher in demented
      compared with nondemented patients. Immunohistochemical analysis showed that SOD
      was expressed in CD68-positive microglial cells while inducible nitric oxide
      synthase was detected in glial fibrillary acidic protein (GFAP)-positive
      astrocytes and in equal amounts in microglial cells. Approximately 70% of the HIV
      p24-Ag-positive macrophages did express SOD, suggesting a direct HIV-induced
      intracellular event. HIV-1 infection of macrophages resulted in both increased
      superoxide anion production and elevated SOD mRNA levels, compared with
      uninfected macrophages. Finally, we show that nitrotyrosine, the footprint of
      peroxynitrite, was found more intense and frequent in brain sections of demented
      patients compared with nondemented patients. These results indicate that, as a
      result of simultaneous production of superoxide anion and nitric oxide,
      peroxynitrite may contribute to the neuropathogenesis of HIV-1 infection.

PMID- 10201966
TI  - Contribution of renal secreted complement C3 to the circulating pool in humans.
AB  - Complement C3 produced within the kidney may be an important mediator of local
      inflammatory and immunological injury. The overall level of renal C3 production
      and consequently its contribution to the total circulating C3 level are, however,
      unknown. This was investigated by using the conversion of C3 from recipient to
      donor allotype following renal transplantation. The C3 F and S allotypes of 80
      consecutive renal donor-recipient pairs (148 individuals) were determined by
      amplification refractory mutation system analysis. The extent of allotype
      conversion in C3 F/S mismatched recipients was quantified at different stages
      after transplantation, using an enzyme-linked immunosorbent assay specific for
      the HAV 4-1 polymorphism of C3 that is strongly associated with C3F. Twenty-one
      of the eighty recipients were potentially informative, i.e., were C3 SS
      recipients of C3 FF or FS donor kidneys. In the early postoperative period, donor
      derived C3 (HAV 4-1-positive) was undetectable, increasing to 9.6% of the total
      circulating C3 at times of acute allograft rejection. When graft dysfunction
      occurred from causes other than rejection, donor C3 remained undetectable. After
      stable graft function was attained (3-13 mo after transplantation), donor C3 made
      up 4.5% of the total circulating C3 pool. Our findings demonstrate that human
      transplant kidney in the resting state is a significant source of extrahepatic
      C3. Its heightened local synthesis during rejection episodes suggests a possible
      pathogenic role for C3 in this immunological process.

PMID- 10201965
TI  - Autoantibodies to T cell costimulatory molecules in systemic autoimmune diseases.
AB  - To determine whether antilymphocyte Abs to T cell costimulatory molecules are
      generated in patients with autoimmune diseases and, if they exist, to clarify the
      mechanism of their production and pathological roles, we investigated the
      presence of autoantibodies to CTLA-4 (CD152), CD28, B7-1 (CD80), and B7-2 (CD86)
      in serum samples obtained from patients with various autoimmune diseases and from
      normal subjects using recombinant fusion proteins. In ELISAs, anti-CD28, anti-B7
      1, and anti-B7-2 Abs were rarely seen, whereas anti-CTLA-4 Abs were detected in
      8.2% of the patients with systemic lupus erythematosus, 18.8% of those with
      rheumatoid arthritis, 3.1% of those with systemic sclerosis, 31.8% of those with
      Behcet's disease, 13.3% of those with Sjogren's syndrome, and 0% of healthy
      donors. This reactivity was confirmed by immunoblotting. More importantly, the
      purified anti-CTLA-4 Abs reacted with CTLA-4 expressed on P815 cells by flow
      cytometry. In addition, we found at least three epitopes on the CTLA-4 molecule.
      Furthermore, among the patients with Behcet's disease, uveitis was seen
      significantly less frequently in the anti-CTLA-4 Ab-positive patients. Taken
      collectively, these data indicate that anti-CTLA-4 autoantibodies are generated
      in systemic autoimmune diseases by an Ag-driven mechanism and may modulate the
      immune response in vivo by binding to CTLA-4 on T cells.

PMID- 10201967
TI  - Molecular characterization of American cockroach tropomyosin (Periplaneta
      americana allergen 7), a cross-reactive allergen.
AB  - Inhalation of allergens produced by the American cockroach (Periplaneta
      americana) induces IgE Ab production and the development of asthma in genetically
      predisposed individuals. The cloning and expression in Escherichia coli of P.
      americana tropomyosin allergen have been achieved. The protein shares high
      homology with other arthropod tropomyosins (80% identity) but less homology with
      vertebrate ones (50% identity). The recombinant allergen was produced in E. coli
      as a nonfusion protein with a yield of 9 mg/l of bacterial culture. Both natural
      and recombinant tropomyosins were purified by isoelectric precipitation. P.
      americana allergen 1 (Per a 1) and Per a 7 (tropomyosin) are to date the only
      cross-reacting allergens found in cockroaches. ELISA and Western blot inhibition
      experiments, using natural and recombinant purified tropomyosins from shrimp and
      cockroach, showed that tropomyosin induced cross-reactivity of IgE from patients
      allergic to these allergens, suggesting that this molecule could be a common
      allergen among invertebrates.

PMID- 10201968
TI  - IL-12-mediated NKRP1A up-regulation and consequent enhancement of endothelial
      transmigration of V delta 2+ TCR gamma delta+ T lymphocytes from healthy donors
      and multiple sclerosis patients.
AB  - Gamma delta T lymphocytes are thought to play a role in the pathogenesis of
      multiple sclerosis (MS) contributing to demyelinization and fibrosis in the
      central nervous system. In this study, we show that, in MS patients with active
      disease, the percentage of circulating V delta 2+ gamma delta T cells
      coexpressing NKRP1A is significantly increased compared with healthy donors. V
      delta 2+ and V delta 1+ T cells were sorted from MS patients and healthy
      volunteers and cloned. At variance with V delta 1+ clones, all V delta 2+ clones
      expressed NKRP1A, which was strongly up-regulated upon culture with IL-12; this
      effect was neutralized by specific anti-IL-12 Abs. No up-regulation of NKRP1A by
      IL-12 was noted on V delta 1+ clones. RNase protection assay showed that IL-12R
      beta 2 subunit transcript was significantly less represented in V delta 1+ than V
      delta 2+ clones. This finding may explain the different effect exerted by IL-12
      on these clones. In transendothelial migration assays, V delta 2+ NKRP1A+ clones
      migrated more effectively than V delta 1+ clones, and this migratory potential
      was enhanced following culture with IL-12. Migration was strongly inhibited by
      the F(ab')2 of an anti-NKRP1A Ab, suggesting that this lectin is involved in the
      migration process. We also show that, in freshly isolated PBMC from MS patients,
      the migrated population was enriched for V delta 2+ NKRP1A+ cells. We conclude
      that the expression of NKRP1A on V delta 2+ cells is associated with increased
      ability to migrate across the vascular endothelium and that this phenomenon may
      be regulated by IL-12 present in the microenvironment.

PMID- 10201969
TI  - Protective role of beta-chemokines associated with HIV-specific Th responses
      against perinatal HIV transmission.
AB  - To examine the protective role of cellular immunity in the vertical transmission
      of HIV, we analyzed HIV-specific IL-2 and CTL responses, as well as beta
      chemokine expression in HIV-infected and uninfected infants of HIV+ mothers. Our
      results showed that HIV envelope (env) peptide-specific IL-2 responses associated
      with beta-chemokine production were detectable at birth in the majority of
      uninfected infants of HIV+ mothers. The responses falling to background before
      the infants were 1 yr old were rarely associated with HIV-specific CTL activity.
      Conversely, HIV-specific Th and CTL cellular responses were absent at birth in
      HIV-infected infants. Infants with AIDS-related symptoms exhibited undetectable
      or very low levels of HIV-specific cellular immunity during the first year of
      life, whereas those with a slowly progressive disease showed evidence of such
      immunity between their second and ninth month. The latter group of infected
      infants tested negative for plasma HIV RNA levels shortly after birth, suggesting
      lack of intrauterine exposure to HIV. The presence of HIV-specific Th responses
      at birth in uninfected newborns of HIV+ mothers, but absence of such activities
      in HIV-infected infants without evidence of intrauterine HIV infection, suggests
      that in utero development of HIV-specific Th responses associated with beta
      chemokines could mediate nonlytic inhibition of infection during vertical
      transmission of HIV.

PMID- 10201970
TI  - Cutting edge: sustained expansion of CD8+ T cells requires CD154 expression by Th
      cells in acute graft versus host disease.
AB  - Brief treatment with alphaCD154 Ab has been shown to prevent acute graft versus
      host disease (aGvHD). We extend these data to show that in the absence of CD154
      function, donor T cells are unable to expand or generate high level anti-host CTL
      activity. Using transgenic (Tg) alloreactive CD8+ T cells adoptively transferred
      into allogeneic recipients, we show that short-term expansion of the CD8+ Tg T
      cells occurred in the absence of Th cells, and this short-term expansion could be
      facilitated with an agonistic alphaCD40. While CD40 agonism could enhance short
      term expansion, sustained expansion of CD8+ Tg T cells required bona fide CD154
      expressing CD4+ alloreactive Th cells. While CD154 was necessary for CD8+ Tg T
      cell sustained expansion, IL-2 was also implicated as essential. These
      observations suggest alphaCD154 therapy in GvHD is effective because the
      treatment causes an abortive CD8 alloresponse leading to the exhaustion or
      deletion of alloreactive CD8+ clones preventing the development of disease.

PMID- 10201971
TI  - Cutting edge: recruitment of the CD19/CD21 coreceptor to B cell antigen receptor
      is required for antigen-mediated expression of Bcl-2 by resting and cycling hen
      egg lysozyme transgenic B cells.
AB  - Recruitment of the CD19/CD21 coreceptor is thought to lower the threshold for
      effective signaling through the B cell Ag receptor. We provide evidence
      supporting a second role for coreceptor recruitment, and that is to enhance the
      survival/proliferative potential of the responding B cells. We show that B cell
      Ag receptor signaling in the absence of coreceptor recruitment induces cellular
      accumulation of the anti-apoptotic protein Bcl-xL, whereas CD19-mediated signals
      are required for Bcl-2 accumulation. The expression of both anti-apoptotic
      proteins correlates with the enhanced responsiveness of both resting and cycling
      B cells to growth-promoting signals delivered through CD40. These results provide
      further evidence for the necessity of coreceptor recruitment during Ag-dependent
      B cell activation and indicate that Ags derived from inflammatory sites function
      as better thymus-dependent Ags than their counterparts not coated with complement
      fragments.

PMID- 10201972
TI  - Cutting edge: phorbol ester induction of IFN-gamma receptors leads to enhanced DR
      alpha gene expression.
AB  - We observed that IFN-gamma-inducible expression of the DR alpha gene was enhanced
      when THP-1 cells are differentiated into macrophage-like cells by phorbol ester
      treatment. Here, we observed that class II MHC trans-activator and STAT1 alpha
      mRNA, mediators of the signaling cascade from the IFN-gamma receptor to the DR
      alpha induction, were markedly increased by IFN-gamma stimulation in phorbol
      ester-activated THP-1 cells; however, both mRNAs were not increased by phorbol
      ester treatment alone. Then, we demonstrated that the mRNA and proteins of the
      IFN-gamma receptor alpha- and beta-chains were amplified by phorbol ester
      treatment in THP-1 cells. Consequently, these results indicate that the
      enhancement of DR alpha gene expression by IFN-gamma treatment in phorbol ester
      activated THP-1 cells is due to the phorbol ester-induced up-regulation of IFN
      gamma receptor alpha- and beta-chains. As a result, the amplification of STAT1
      alpha and the increment of class II MHC trans-activator results in enhancement of
      DR alpha expression.

PMID- 10201973
TI  - Cutting edge: effects of an allergy-associated mutation in the human IL-4R alpha
      (Q576R) on human IL-4-induced signal transduction.
AB  - A mutation in the human (hu) IL-4R alpha, Q576R, has been linked with allergy in
      humans. Increased sensitivity of patients cells with this mutation to IL-4
      suggest that a Q576R change enhances IL-4 signaling. To directly test this
      hypothesis, we analyzed the ability of huIL-4R alpha cDNA bearing the Q576R and
      Y575F mutations to signal tyrosine phosphorylation, DNA-binding activity,
      proliferation, protection from apoptosis, and CD23 induction in response to huIL
      4 in murine cells. Responses generated by the Q576R and Y575F mutants were
      similar to those of the wild-type receptor, using various concentrations of huIL
      4 and times of stimulation. These results indicate that neither the Q576R nor the
      Y575F mutations have a significant direct effect on IL-4 signal transduction, and
      that hypersensitive induction of CD23 in cells derived from human allergy
      patients may be due to different and/or additional alterations in the IL-4
      signaling pathway.

PMID- 10201974
TI  - Evidence of alternative or concomitant use of perforin- and Fas-dependent
      pathways in a T cell-mediated negative regulation of Ig production.
AB  - To study the possible involvement of perforin (Pfp)- and/or Fas-dependent
      cytotoxicity pathways in a T cell-mediated negative regulation of Ig production,
      we used the T cell-induced Ig-allotype suppression model. T splenocytes from
      Igha/a mice, when neonatally transferred into histocompatible Igha/b F1 or Ighb/b
      congenic hosts, are intrinsically able to totally, specifically, and chronically
      suppress the production of IgG2a of the Ighb haplotype (IgG2ab). It has not been
      established whether the suppression effectors, which are anti-IgG2ab MHC class I
      restricted CD8+ T cells, cytolyse IgG2ab+ B targets or whether they only silence
      Ig production. In this study, using T cells from Igha/a Pfp+/+ or Pfpo/o mice,
      the latter obtained by crossbreeding, and B cells from Ighb/b Fas+/+ or
      Faslpr/lpr (lymphoproliferation) mice in appropriate adoptive transfer models, we
      demonstrated that: 1) under blockage of the Pfp-mediated pathway, Igha/a T cells
      were still able to induce suppression against wild-type IgG2ab+ B cells, 2)
      IgG2ab+ B cells with impaired Fas expression were also subjected to suppression
      by WT Igha/a T splenocytes, and 3) the suppression establishment was totally
      inhibited when both Pfp- and Fas-dependent mechanisms were simultaneously
      blocked, i.e., when Igha/a Pfpo/o T cells were used to induce suppression against
      Ighb/b Faslpr/lpr B cells. These results provide the first demonstration of the
      existence of alternative or simultaneous use of the major cytotoxic mechanisms in
      a T cell-mediated down-regulation of an Ig production.

PMID- 10201975
TI  - The dependence for leukocyte function-associated antigen-1/ICAM-1 interactions in
      T cell activation cannot be overcome by expression of high density TCR ligand.
AB  - The leukocyte-specific integrin, LFA-1, can enhance T cell activation. However,
      it is unclear whether the binding of LFA-1 to its ligand, ICAM-1, functions
      through intercellular adhesion alone, resulting in an augmentation of the TCR
      signal, or involves an additional LFA-1-mediated cellular signal transduction
      pathway. We have previously shown that naive CD4+ lymph node T cells, isolated
      from DO11.10 TCR transgenic mice, are activated by increasing doses of exogenous
      OVA peptide presented by transfectants expressing both class II and ICAM-1, but
      not by cells expressing class II alone. To determine whether LFA-1/ICAM-1
      interactions were simply enhancing the presentation of low concentrations of
      specific MHC/peptide complexes generated from exogenously added peptide, we
      transfected cells with class II that is covalently coupled to peptide, alone or
      in combination with ICAM-1. These cells express 100-fold more specific class
      II/peptide complexes than can be loaded onto class II-positive cells at maximum
      concentrations of exogenous peptide. Despite this high density of TCR ligand,
      activation of naive CD4+ T cells still requires the coexpression of ICAM-1. LFA
      1/ICAM-1 interactions are not required for effective conjugate formation and TCR
      engagement because presentation of class II/peptide complexes in the absence of
      ICAM-1 does induce up-regulation of CD25 and CD69. Thus, high numbers of engaged
      TCR cannot compensate for the lack of LFA-1/ICAM-1 interactions in the activation
      of naive CD4+ T cells.

PMID- 10201976
TI  - Production of high affinity autoantibodies in autoimmune New Zealand Black/New
      Zealand white F1 mice targeted with an anti-DNA heavy chain.
AB  - Lupus-prone, anti-DNA, heavy (H) chain "knock-in" mice were obtained by
      backcrossing C57BL/6 mice, targeted with a rearranged H chain from a VH11(S107)
      encoded anti-DNA hybridoma (D42), onto the autoimmune genetic background of New
      Zealand Black/New Zealand White (NZB/NZW) F1 mice. The targeted female mice
      developed typical lupus serologic manifestations, with the appearance of
      transgenic IgM anti-DNA autoantibodies at a young age (2-3 mo) and high affinity,
      somatically mutated IgM and IgG anti-DNA Abs at a later age (6-7 mo). However,
      they did not develop clinical, lupus-associated glomerulonephritis and survived
      to at least 18 mo of age. L chain analysis of transgenic anti-DNA Abs derived
      from diseased NZB/NZW mouse hybridomas showed a very restricted repertoire of
      Vkappa utilization, different from that of nonautoimmune (C57BL/6 x BALB/c)F1
      transgenic anti-DNA Abs. Strikingly, a single L chain was repetitively selected
      by most anti-DNA, transgenic NZB/NZW B cells to pair with the targeted H chain.
      This L chain had the same Vkappa-Jkappa rearrangement as that expressed by the
      original anti-DNA D42 hybridoma. These findings indicate that the kinetics of the
      autoimmune serologic manifestations are similar in wild-type and transgenic lupus
      prone NZB/NZW F1 mice and suggest that the breakdown of immunologic tolerance in
      these mice is associated with the preferential expansion and activation of B cell
      clones expressing high affinity anti-DNA H/L receptor combinations.

PMID- 10201977
TI  - Accelerated emigration of B lymphocytes in the Xid mouse.
AB  - The B cell receptor is required for the emigration of newly generated B
      lymphocytes and for their maintenance in the periphery. A specific maintenance
      defect was noted in fraction I (IgDhighIgMlow) B cells in Xid mice (which harbor
      a mutation in Btk). Although Bcl-2 levels in fractions I and II (IgDhighIgMhigh)
      are equivalent in normal and Xid B cells, a novel peak of Bcl-2low fraction III
      (IgDlowIgMhigh) B cells was noted in the Xid mouse. Since this B cell population
      resembled bone marrow immature B cells, we examined the emigration of newly
      formed B cells in normal and Xid mice. These studies revealed the accelerated
      emigration of newly formed Xid B cells. We conclude that distinct Btk-independent
      and Btk-dependent signals mediate emigration and maintenance events during
      peripheral B cell maturation.

PMID- 10201978
TI  - Negative regulation of c-kit-mediated cell proliferation by Fc gamma RIIB.
AB  - Fc gamma RIIB are single-chain low-affinity receptors for IgG that bear an
      immunoreceptor tyrosine-based inhibition motif in their intracytoplasmic domain
      and that negatively regulate immunoreceptor tyrosine-based activation motif
      dependent cell activation. They are widely expressed by cells of hematopoietic
      origin. We investigated here whether Fc gamma RIIB could also negatively regulate
      protein tyrosine kinase receptor (RTK)-dependent cell proliferation. As an
      experimental model, we used growth factor-dependent mast cells that
      constitutively express Fc gamma RIIB and c-kit, an RTK prototype. We found that
      anti-c-kit Abs mimicked the effect of stem cell factor and induced thymidine
      incorporation in Fc gamma RIIB-/-, but not in wild-type (wt) mast cells unless Fc
      gamma RIIB were blocked or anti-c-kit F(ab')2 were used. When coaggregated with c
      kit by intact Abs in wt mast cells, Fc gamma RIIB inhibited thymidine
      incorporation, as well as cell proliferation, and inhibition was correlated with
      an arrest of cells in G1 during the cell cycle. The coaggregation of c-kit with
      Fc gamma RIIB did not affect ligand-induced c-kit phosphorylation and induced the
      tyrosyl-phosphorylation of Fc gamma RIIB, which selectively recruited the Src
      homology 2 domain-bearing inositol 5-phosphatase SHIP. Our results indicate that
      IgG Abs to growth factors or growth factor receptors may control RTK-dependent
      proliferation of a variety of cells that express Fc gamma RIIB.

PMID- 10201979
TI  - MHC class I-restricted presentation of maleylated protein binding to scavenger
      receptors.
AB  - Pathways for loading exogenous protein-derived peptides on MHC class I are
      thought to be present mainly in monocyte-lineage cells and to involve
      phagocytosis- or macropinocytosis-mediated antigenic leakage into either cytosol
      or extracellular milieu to give peptide access to MHC class I. We show that
      maleylation of OVA enhanced its presentation to an OVA-specific MHC class I
      restricted T cell line by both macrophages and B cells. This enhanced
      presentation involved uptake through receptors of scavenger receptor (SR)-like
      ligand specificity, was TAP-1-independent, and was inhibited by low levels (2 mM)
      of ammonium chloride. No peptide loading of bystander APCs by maleylated (maleyl)
      OVA-pulsed macrophages was detected. Demaleylated maleyl-OVA showed enhanced MHC
      class I-restricted presentation through receptor-mediated uptake and remained
      highly sensitive to 2 mM ammonium chloride. However, if receptor binding of
      maleyl-OVA was inhibited by maleylated BSA, the residual presentation was
      relatively resistant to 2 mM ammonium chloride. Maleyl-OVA directly introduced
      into the cytosol via osmotic lysis of pinosomes was poorly presented, confirming
      that receptor-mediated presentation of exogenous maleyl-OVA was unlikely to
      involve a cytosolic pathway. Demaleylated maleyl-OVA was well presented as a
      cytosolic Ag, consistent with the dependence of cytosolic processing on protein
      ubiquitination. Thus, receptor-specific delivery of exogenous protein Ags to APCs
      can result in enhanced MHC class I-restricted presentation, suggesting that the
      exogenous pathway of peptide loading for MHC class I may be a constitutive
      property dependent mainly on the quantity of Ag taken up by APCs.

PMID- 10201980
TI  - Phosphorylation of CD19 Y484 and Y515, and linked activation of
      phosphatidylinositol 3-kinase, are required for B cell antigen receptor-mediated
      activation of Bruton's tyrosine kinase.
AB  - Bruton's tyrosine kinase (Btk) plays a critical role in B cell Ag receptor (BCR)
      signaling, as indicated by the X-linked immunodeficiency and X-linked
      agammaglobulinemia phenotypes of mice and men that express mutant forms of the
      kinase. Although Btk activity can be regulated by Src-family and Syk tyrosine
      kinases, and perhaps by phosphatidylinositol 3,4,5-trisphosphate, BCR-coupled
      signaling pathways leading to Btk activation are poorly understood. In view of
      previous findings that CD19 is involved in BCR-mediated phosphatidylinositol 3
      kinase (PI3-K) activation, we assessed its role in Btk activation. Using a CD19
      reconstituted myeloma model and CD19 gene-ablated animals we found that BCR
      mediated Btk activation and phosphorylation are dependent on the expression of
      CD19, while BCR-mediated activation of Lyn and Syk is not. Wortmannin
      preincubation inhibited the BCR-mediated activation and phosphorylation of Btk.
      Btk activation was not rescued in the myeloma by expression of a CD19 mutant in
      which tyrosine residues previously shown to mediate CD19 interaction with PI3-K,
      Y484 and Y515, were changed to phenylalanine. Taken together, the data presented
      indicate that BCR aggregation-driven CD19 phosphorylation functions to promote
      Btk activation via recruitment and activation of PI3-K. Resultant
      phosphatidylinositol 3,4,5-trisphosphate probably functions to localize Btk for
      subsequent phosphorylation and activation by Src and Syk family kinases.

PMID- 10201981
TI  - TNF receptor-associated factor-2 is involved in both IL-1 beta and TNF-alpha
      signaling cascades leading to NF-kappa B activation and IL-8 expression in human
      intestinal epithelial cells.
AB  - Cytokine signaling involves the participation of many adaptor proteins, including
      the docking protein TNF receptor-associated factor-2 (TRAF-2), which is believed
      to transmit the TNF-alpha signal through both the I kappa B/NF-kappa B and c-Jun
      N-terminal kinase (JNK)/stress-related protein kinase (SAPK) pathways. The
      physiological role of TRAF proteins in cytokine signaling in intestinal
      epithelial cells (IEC) is unknown. We characterized the effect of a dominant
      negative TRAF-2 delivered by an adenoviral vector (Ad5dnTRAF-2) on the cytokine
      signaling cascade in several IEC and also investigated whether inhibiting the
      TRAF-2-transmitting signal blocked TNF-alpha-induced NF-kappa B and IL-8 gene
      expression. A high efficacy and level of Ad5dnTRAF-2 gene transfer were obtained
      in IEC using a multiplicity of infection of 50. Ad5dnTRAF-2 expression prevented
      TNF-alpha-induced, but not IL-1 beta-induced, I kappa B alpha degradation and NF
      kappa B activation in NIH-3T3 and IEC-6 cells. TNF-alpha-induced JNK activation
      was also inhibited in Ad5dnTRAF-2-infected HT-29 cells. Induction of IL-8 gene
      expression by TNF-alpha was partially inhibited in Ad5dnTRAF-2-transfected HT-29,
      but not in control Ad5LacZ-infected, cells. Surprisingly, IL-1 beta-mediated IL-8
      gene expression was also inhibited in HT-29 cells as measured by Northern blot
      and ELISA. We concluded that TRAF-2 is partially involved in TNF-alpha-mediated
      signaling through I kappa B/NF-kappa B in IEC. In addition, our data suggest that
      TRAF-2 is involved in IL-1 beta signaling in HT-29 cells. Manipulation of
      cytokine signaling pathways represents a new approach for inhibiting
      proinflammatory gene expression in IEC.

PMID- 10201982
TI  - Antigen receptor engagement selectively induces macrophage inflammatory protein-1
      alpha (MIP-1 alpha) and MIP-1 beta chemokine production in human B cells.
AB  - We show herein that B cell Ag receptor (BCR) triggering, but not stimulation by
      CD40 mAb and/or IL-4, rapidly induced the coordinated expression of two closely
      related T cell chemoattractants, macrophage inflammatory protein-1 beta (MIP-1
      beta) and MIP-1 alpha, by human B cells. Naive, memory, and germinal center B
      cells all produced MIP-1 alpha/beta in response to BCR triggering. In contrast to
      MIP-1 alpha/beta, IL-8, which is spontaneously produced by germinal center B
      cells but not by naive and memory B cells, was not regulated by BCR triggering.
      Culturing follicular dendritic cell-like HK cells with activated B cells did not
      regulate MIP-1 alpha/beta production, but it did induce production of IL-8 by HK
      cells. Microchemotaxis assays showed that CD4+CD45RO+ T cells of the
      effector/helper phenotype actively migrated along a chemotactic gradient formed
      by BCR-stimulated B cells. This effect was partially blocked by anti-MIP-1 beta
      and anti-CC chemokine receptor 5 Ab, but not by anti-MIP-1 alpha Ab suggesting
      that MIP-1 beta plays a major role in this chemoattraction. Since maturation of
      the B cell response to a peptide Ag is mostly dependent on the availability of T
      cell help, the ability of Ag-stimulated B cells to recruit T cells via MIP-1
      alpha/beta, may represent one possible mechanism enabling cognate interactions
      between rare in vivo Ag-specific T and B cells.

PMID- 10201983
TI  - Aberrant CD3- and CD28-mediated signaling events in cord blood T cells are
      associated with dysfunctional regulation of Fas ligand-mediated cytotoxicity.
AB  - There have been numerous reports of decreased acute and chronic graft-vs-host
      disease (GVHD) in patients receiving HLA-matched or HLA-disparate umbilical cord
      transplants. However, little is known about the mechanisms underlying the low
      incidence of GVHD in umbilical cord blood transplantation (CBT). In this study,
      we examined CD3- and CD28-mediated functional properties and signaling events in
      CB T cells (CBTCs). Dual stimulation of peripheral blood TCs (PBTCs) and bone
      marrow TCs (BMTCs) with mAbs to CD3- and CD28-induced expressions of Fas ligand
      (FasL), as well as CD25 and CD154 (CD40L), whereas defective induction of these
      activation-associated cell surface molecules were observed in CBTCs. Engagement
      of both CD3 and CD28 induced FasL-mediated cytotoxicity in peripheral blood TCs
      (PBTCs) but not CBTCs; however, both of these tissue sources possess
      intrinsically similar proliferative responsiveness. Analysis of CD3- and CD28
      induced signal transduction revealed a deficiency in signaling events that
      involved repressed tyrosine phosphorylation and enzymatic activities of a family
      of mitogen-activated protein kinases, extracellular signal-regulated kinase 2,
      stress-activated protein kinase/c-jun N-terminal kinase (SAPK/JNK), and p38mapk,
      as well as p56lck and ZAP-70 in CBTCs compared with those in PBTCs. These results
      suggest that CD3- and CD28-mediated signaling events blockage in CBTCs may be
      responsible for dysfunction of FasL-mediated cytotoxicity and lead to the low
      incidence of severe GVHD in CBT.

PMID- 10201984
TI  - The functional synergy between IL-12 and IL-2 involves p38 mitogen-activated
      protein kinase and is associated with the augmentation of STAT serine
      phosphorylation.
AB  - IL-12 and IL-2 can stimulate mitogen- or CD3-activated T cells to proliferate,
      produce IFN-gamma, and kill tumor cells. The magnitude of these functional
      responses is greatly augmented when T cells are activated by the combination of
      IL-12 and IL-2. Although peripheral blood T cells are largely unresponsive to
      these cytokines without prior activation, a small subset of CD8+ T cells
      (CD8+CD18bright) is strongly activated by the combination of IL-12 and IL-2. In
      this report we show that the functional synergy between IL-12 and IL-2 in
      CD8+CD18bright T cells correlates with the activation of the stress kinases, p38
      mitogen-activated protein (MAP) kinase and stress-activated protein kinase
      (SAPK)/Jun N-terminal kinase, but not with the activation of the extracellular
      signal-regulated kinases. The functional synergy between IL-2 and IL-12 is also
      associated with a prominent increase in STAT1 and STAT3 serine phosphorylation
      over that observed with IL-12 or IL-2 alone. By contrast, STAT tyrosine
      phosphorylation is not augmented over that seen with either cytokine alone. A
      specific inhibitor of p38 MAP kinase completely inhibits the serine
      phosphorylation of STAT1 and STAT3 induced by IL-12 and IL-2 and abrogates the
      functional synergy between IL-12 and IL-2 without affecting STAT tyrosine
      phosphorylation. This suggests that p38 MAP kinase may play an important role in
      regulating STAT serine phosphorylation in response to the combination of IL-12
      and IL-2. Furthermore, these findings indicate that the optimal activation of T
      cells by IL-12 and IL-2 may depend on an interaction between the p38 MAP kinase
      and Janus kinase/STAT signaling pathways.

PMID- 10201985
TI  - T cell immunity induced by allogeneic microglia in relation to neuronal retina
      transplantation.
AB  - Microglia share a lineage relationship with bone marrow-derived
      monocytes/macrophages and dendritic cells, and their inclusion in retinal and
      brain transplants may function as "passenger leukocytes. " In other solid
      allografts, passenger leukocytes are the primary sources of immunogenicity,
      triggering alloimmune rejection. We have conducted a series of in vitro and in
      vivo studies examining the capacity of microglia cultured from forebrain to
      activate alloreactive T cells and to induce and elicit alloimmunity. Cultured
      microglia expressed class II MHC molecules and costimulatory molecules (B7-1, B7
      2, and CD40), and they secreted IL-12. Cultured microglia injected s.c. into
      naive recipients induced allospecific delayed hypersensitivity and elicited
      delayed hypersensitivity directed at alloantigens. Cultured microglia differed
      from conventional APCs by secreting significant amounts of mature TGF-beta2, but
      smaller amounts of IL-12. Moreover, while both cultured microglia and
      conventional APC stimulated T cell proliferation in vitro, microglia directed the
      responding T cells toward the Th2 pathway in which IL-4, but not IL-2 and IFN
      gamma, was secreted. The abilities of microglia to secrete TGF-beta2, to
      stimulate alloreactive Th2 cells, and to induce anterior chamber associated
      immune deviation when injected into the eye of naive allogeneic mice suggest that
      they are not typical passenger leukocytes. The unique functional properties of
      cultured microglia may account for the capacity of neonatal retinal tissue
      transplanted into the eye to alter the systemic alloimmune response in a manner
      that delays, but does not prevent, graft rejection.

PMID- 10201986
TI  - CD28 costimulation is crucial for the development of spontaneous autoimmune
      encephalomyelitis.
AB  - Multiple sclerosis (MS) is a severe central nervous system disease. Experimental
      autoimmune encephalomyelitis (EAE) mimics MS in mice. We report that spontaneous
      development of EAE in RAG-1-deficient mice transgenic for a myelin basic protein
      (MBP)-specific TCR (TgMBP+/RAG-1-/-) requires expression of the T cell
      costimulatory molecule CD28. Surprisingly, T cells from CD28-/-TgMBP+/RAG-1-/-
      mice proliferate and produce IL-2 in response to MBP1-17 peptide in vitro,
      excluding clonal anergy as the mechanism of CD28-regulated pathogenesis.
      Proliferation of autoaggressive T cells was dependent on the concentration of the
      MBP peptide, as was the development of MBP-induced EAE in CD28-deficient PL/J
      mice. These results provide the first genetic evidence that CD28 costimulation is
      crucial for MBP-specific T cell activation in vivo and the initiation of
      spontaneous EAE.

PMID- 10201987
TI  - Modulation of allospecific CTL responses during pregnancy in equids: an
      immunological barrier to interspecies matings?
AB  - Maternal immune recognition of the developing conceptus in equine pregnancy is
      characterized by the strongest and most consistent alloantibody response
      described in any species, a response directed almost exclusively against paternal
      MHC class I Ags. This work investigated the cellular immune response to paternal
      MHC Ags in pregnant and nonpregnant horses and donkeys, and in horses carrying
      interspecies hybrid mule conceptuses. We observed profound decreases in
      classical, MHC-restricted, CTL activity to allogeneic paternal cells in
      peripheral blood lymphocytes from both horse mares and donkey jennets carrying
      intraspecies pregnancies, compared with cells from nonpregnant controls. This is
      the first evidence in a randomly bred species for a generalized systemic shift of
      immune reactivity away from cellular and toward humoral immunity during
      pregnancy. Surprisingly, mares carrying interspecies hybrid mule conceptuses did
      not exhibit this transient, pregnancy-associated decrease in CTL activity. The
      failure of interspecies pregnancy to down-regulate cellular immune responses may
      be a heretofore-unrecognized, subtle barrier to reproductive success between
      species.

PMID- 10201988
TI  - Biochemical and immunogenetic analysis of an immunodominant peptide (B6dom1)
      encoded by the classical H7 minor histocompatibility locus.
AB  - Of the many minor histocompatibility (H) Ags that have been detected in mice, the
      ability to induce graft vs host disease (GVHD) after bone marrow transplantation
      is restricted to a limited number of immunodominant Ags. One such murine Ag,
      B6dom1, is presented by the H2-Db MHC class I molecule. We present biochemical
      evidence that the natural B6dom1 peptide is indistinguishable from AAPDNRETF, and
      we show that this peptide can be isolated from a wide array of tissues, with
      highest levels from the lymphoid organs and lung. Moreover, we employ a novel,
      somatic cell selection technique involving CTL-mediated immunoselection coupled
      with classical genetics, to show that B6dom1 is encoded by the H7 minor H locus
      originally discovered approximately 40 years ago. These studies provide a
      molecular genetic framework for understanding B6dom1, and exemplify the fact that
      mouse minor H loci that encode immunodominant CTL epitopes can correspond to
      classical H loci originally identified by their ability to confer strong
      resistance to tumor transplantation. Additionally, these studies demonstrate the
      utility of somatic cell selection approaches toward resolving H Ag
      immunogenetics.

PMID- 10201989
TI  - Differential cytokine and chemokine gene expression by human NK cells following
      activation with IL-18 or IL-15 in combination with IL-12: implications for the
      innate immune response.
AB  - NK cells constitutively express monocyte-derived cytokine (monokine) receptors
      and secrete cytokines and chemokines following monokine stimulation, and are
      therefore a critical component of the innate immune response to infection. Here
      we compared the effects of three monokines (IL-18, IL-15, and IL-12) on human NK
      cell cytokine and chemokine production. IL-18, IL-15, or IL-12 alone did not
      stimulate significant cytokine or chemokine production in resting NK cells. The
      combination of IL-18 and IL-12 induced extremely high amounts of IFN-gamma
      protein (225 +/- 52 ng/ml) and a 1393 +/- 643-fold increase in IFN-gamma gene
      expression over those in resting NK cells. IL-15 and IL-12 induced less IFN-gamma
      protein (24 +/- 10 ng/ml; p < 0.007) and only a 45 +/- 19-fold increase in IFN
      gamma gene expression over those in resting NK cells. The CD56bright NK cell
      subset produced significantly more IFN-gamma following IL-18 and IL-12 compared
      with CD56dim NK cells (p < 0.008). However, the combination of IL-15 and IL-12
      was significantly more potent than that of IL-18 and IL-12 for NK cell production
      of IL-10, macrophage inflammatory protein-1alpha, macrophage inflammatory protein
      1beta, and TNF-alpha at the protein and transcript levels. Granulocyte-macrophage
      CSF was optimally induced by IL-15 and IL-18. Resting CD56+ NK cells expressed IL
      18R transcript that was up-regulated by IL-12 or IL-15. Our results show that
      distinct cytokine and chemokine patterns are induced in NK cells in response to
      different costimulatory signals from these three monokines. This suggests that NK
      cell cytokine production may be governed in part by the monokine milieu induced
      during the early proinflammatory response to infection and by the subset of NK
      cells present at the site of inflammation.

PMID- 10201990
TI  - Virus-induced CD8+ T cell clonal expansion is associated with telomerase up
      regulation and telomere length preservation: a mechanism for rescue from
      replicative senescence.
AB  - In acute infectious mononucleosis (AIM), very large clones of Ag-specific CD8+
      effector T cells are generated. Many clones persist as memory cells, although the
      clone size is greatly reduced. It would be expected that the large number of cell
      divisions occurring during clonal expansion would lead to shortening of
      telomeres, predisposing to replicative senescence. Instead, we show that clonally
      expanded CD8+ T cells in AIM have paradoxical preservation of telomere length in
      association with marked up-regulation of telomerase. We postulate that this
      allows a proportion of responding T cells to enter the memory pool with a
      preserved capacity to continue dividing so that long-term immunological memory
      can be maintained.

PMID- 10201991
TI  - Bystander virus infection prolongs activated T cell survival.
AB  - In animals, T cells often die rapidly after activation, unless activation occurs
      in the presence of inflammatory factors. To understand how such activated cells
      survive to participate in immune responses, we studied the effects of viral
      infection on T cells responding to an unrelated superantigen. Normal T cells
      activated by superantigen in uninfected mice died as a result of their
      activation, whereas T cells that were activated during vaccinia infection
      survived longer in vivo and in culture. This bystander effect of viral infection
      on activated T cells was independent of effects on the magnitude of the initial T
      cell response, on induction of Bcl-2 and Bcl-x, on T cell proliferation, and on
      Fas killing. The failure of such effects to predict the fate of activated T cells
      in vivo indicates that virus infections shape T cell responses via mechanisms
      that differ from those described previously. These mechanisms may contribute to
      the ability of viral infections to induce autoimmunity.

PMID- 10201992
TI  - In vivo selection of neutralization-resistant virus variants but no evidence of B
      cell tolerance in lymphocytic choriomeningitis virus carrier mice expressing a
      transgenic virus-neutralizing antibody.
AB  - B cell tolerance is maintained by active deletion and functional anergy of self
      reactive B cells depending on the time, amount, and site of the self-antigen
      expression. To study B cell tolerance toward a transplacentally transmitted viral
      Ag, we crossed transgenic mice expressing the mu heavy and the kappa light chain
      of the lymphocytic choriomeningitis virus (LCMV)-neutralizing mAb KL25 (HL25
      transgenic mice) with persistently infected LCMV carrier mice. Although HL25
      transgenic LCMV carrier mice exhibited the same high virus titers as
      nontransgenic LCMV carrier mice, no evidence for B cell tolerance was found. In
      contrast, enhanced LCMV-neutralizing Ab titers were measured that, however, did
      not clear the virus. Instead, LCMV isolates from different tissues turned out to
      be neutralization resistant Ab escape variants expressing different substitutions
      of amino acid Asn119 of the LCMV-glycoprotein 1 that displays the neutralizing B
      cell epitope. Virus variants with the same mutations were also selected in vitro
      in the presence of the transgenic mAb KL25 confirming that substitutions of
      Asn119 have been selected by LCMV-neutralizing Abs. Thus, despite abundant
      expression of viral neo-self-antigen in HL25-transgenic LCMV carrier mice,
      transgenic B cells expressing LCMV-neutralizing Abs were rather stimulated than
      tolerized and neutralization resistant Ab escape variants were selected in vivo.

PMID- 10201993
TI  - Phosphatidylinositol 3'-kinase, but not S6-kinase, is required for insulin-like
      growth factor-I and IL-4 to maintain expression of Bcl-2 and promote survival of
      myeloid progenitors.
AB  - Phosphatidylinositol 3'-kinase (PI 3-kinase) catalyzes the formation of 3'
      phosphoinositides and has been implicated in an intracellular signaling pathway
      that inhibits apoptosis in both neuronal and hemopoietic cells. Here, we
      investigated two potential downstream mediators of PI 3-kinase, the
      serine/threonine p70 S6-kinase (S6-kinase) and the antiapoptotic protein B cell
      lymphoma-2 (Bcl-2). Stimulation of factor-dependent cell progenitor (FDCP) cells
      with either IL-4 or insulin-like growth factor (IGF)-I induced a 10-fold increase
      in the activity of both PI 3-kinase and S6-kinase. Rapamycin blocked 90% of the
      S6-kinase activity but did not affect PI 3-kinase, whereas wortmannin and
      LY294002 inhibited the activity of both S6-kinase and PI 3-kinase. However,
      wortmannin and LY294002, but not rapamycin, blocked the ability of IL-4 and IGF-I
      to promote cell survival. We next established that IL-3, IL-4, and IGF-I increase
      expression of Bcl-2 by >3-fold. Pretreatment with inhibitors of PI 3-kinase, but
      not rapamycin, abrogated expression of Bcl-2 caused by IL-4 and IGF-I, but not by
      IL-3. None of the cytokines affected expression of the proapoptotic protein Bax,
      suggesting that all three cytokines were specific for Bcl-2. These data establish
      that inhibition of PI 3-kinase, but not S6-kinase, blocks the ability of IL-4 and
      IGF-I to increase expression of Bcl-2 and protect promyeloid cells from
      apoptosis. The requirement for PI 3-kinase to maintain Bcl-2 expression depends
      upon the ligand that activates the cell survival pathway.

PMID- 10201994
TI  - Unique superantigen activity of staphylococcal exfoliative toxins.
AB  - Certain strains of Staphylococcus aureus express one or both of two related, but
      immunologically distinct, exfoliative toxins (ETA and ETB). These toxins induce
      the symptoms associated with staphylococcal scalded skin syndrome. Both ETs have
      been shown to stimulate T cell proliferation. Recently, it was reported that ETA
      is a superantigen that stimulates T cells bearing human Vbeta2 or several murine
      Vbetas. However, other investigators have proposed that the superantigenicity
      reported for ETA resulted from contaminants in commercial preparations. This
      present study addresses those conflicting reports by assessing the biological and
      immunologic activities of highly purified rETs. ETA and ETB required APCs to
      induce selective polyclonal expansion of several human Vbetas (huVbetas),
      although, neither toxin expanded huVbeta2. ETB induced expansion of murine T
      cells bearing Vbetas 7 and 8, those that have the highest homology to the
      huVbetas expanded by ETA and ETB. Although flow cytometry of ETB-stimulated T
      cells matched PCR results, stimulation by ETA reduced percentages of T cells
      positive for several huVbetas that had been shown to have increased levels of
      mRNA transcripts. ETA and ETB induced contrasting reactions in vivo. In rabbits,
      ETB was moderately pyrogenic and enhanced susceptibility to lethal shock, while
      ETA lacked both activities. Predictions based on comparisons with other
      superantigens suggest molecular regions potentially involved in receptor binding
      in the ETA crystal structure and a modeled ETB three-dimensional structure. These
      results show that ETs are superantigens with unique properties that could account
      for the discrepancies reported.

PMID- 10201995
TI  - Expression of CD1d2 on thymocytes is not sufficient for the development of NK T
      cells in CD1d1-deficient mice.
AB  - CD1 is an MHC class I-like molecule that has been conserved throughout mammalian
      evolution. Unlike MHC class I molecules, CD1 can present unique nonprotein
      antigens to T cells. The murine CD1 locus contains two highly homologous genes,
      CD1d1 and CD1d2. CD1d1 is essential for the development of a major subset of NK T
      cells that promptly secrete IL-4 following activation. However, the function of
      CD1d2 has not yet been demonstrated. In the present study, we examined the
      expression of CD1d2 in CD1d1-deficient (CD1d1 degrees) mice with the anti-CD1 Ab
      3H3. Unlike CD1d1, which is expressed by all lymphocytes, CD1d2 can be detected
      only on the surface of thymocytes. To determine whether CD1d2 can select a unique
      subset of NK T cells, we compared the remnant population of NK T cells in CD1d1
      degrees and CD1d1, CD1d2-double deficient (CD1d1 degrees CD1d2 degrees) mice. No
      significant difference in the number of NK T cells and cytokine secretion
      capacity can be detected between CD1d1 degrees and CD1d1 degrees CD1d2 degrees
      mice, indicating that CD1d2 cannot substitute for CD1d1 in NK T cell development.
      The inability of CD1d2 to select NK T cells is not due to the structural
      constraints of CD1d2 since CD1d2-transfected cells can be recognized by both NK T
      cell hybridomas and freshly isolated NK T cells. Given the structural
      similarities, it is possible that the low levels of surface expression and
      limited tissue distribution of CD1d2 may prevent it from functioning in the
      selection and expansion of NK T cells.

PMID- 10201997
TI  - Pancreatic infiltration but not diabetes occurs in the relative absence of MHC
      class II-restricted CD4 T cells: studies using NOD/CIITA-deficient mice.
AB  - The NOD (nonobese diabetic) mouse is a good animal model for human IDDM. MHC
      class II-restricted CD4 T cells are necessary for the onset of diabetes in NOD
      mice. Here, we demonstrate that NOD mice lacking the CIITA (class II
      transactivator) molecule, and hence deficient in MHC class II expression and
      peripheral CD4 T cells, show significant pancreatic infiltration but do not
      develop diabetes. CD4 T cell deficiency, then, does not prevent initial
      pancreatic infiltration, but does stop progression to insulitis. Adoptive
      transfer studies show that the paucity of CD4 T cells in NOD-CIITA knockout mice
      is responsible for the absence of diabetes, since the CD8 T cell and B cell
      compartments are functional. An autoaggressive CD8+ T cell clone can, however,
      transfer diabetes in CIITA knockout recipient mice without CD4 T cell help,
      albeit with some delay compared with that in CIITA-sufficient recipients. This
      highlights the fact that a high number of in vitro activated autoaggressive CD8 T
      cells can over-ride the requirement for CD4 T cell help for the onset of
      diabetes.

PMID- 10201996
TI  - TGF-beta 1 prevents the noncognate maturation of human dendritic Langerhans
      cells.
AB  - TGF-beta 1 is critical for differentiation of epithelial-associated dendritic
      Langerhans cells (LC). In accordance with the characteristics of in vivo LC, we
      show that LC obtained from human monocytes in vitro in the presence of TGF-beta 1
      1) express almost exclusively intracellular class II Ags, low CD80, and no CD83
      and CD86 Ags and 2) down-regulate TNF-RI (p55) and do not produce IL-10 after
      stimulation, in contrast to dermal dendritic cells and monocyte-derived dendritic
      cells. Surprisingly, while LC exhibit E-cadherin down-regulation upon exposure to
      TNF-alpha and IL-1, TGF-beta 1 prevents the final LC maturation in response to
      TNF-alpha, IL-1, and LPS with respect to Class II CD80, CD86, and CD83 Ag
      expression, loss of FITC-dextran uptake, production of IL-12, and Ag
      presentation. In sharp contrast, CD40 ligand cognate signal induces full
      maturation of LC and is not inhibited by TGF-beta 1. The presence of emigrated
      immature LCs in human reactive skin-draining lymph nodes provides in vivo
      evidence that LC migration and final maturation may be differentially regulated.
      Therefore, due to the effects of TGF-beta 1, inflammatory stimuli may not be
      sufficient to induce full maturation of LC, thus avoiding potentially harmful
      immune responses. We conclude that TGF-beta 1 appears to be responsible for both
      the acquisition of LC phenotype, cytokine production pattern, and prevention of
      noncognate maturation.

PMID- 10201998
TI  - Differential expression and regulation of cyclooxygenase isozymes in thymic
      stromal cells.
AB  - Prostaglandins (PGs) are lipid-derived mediators of rapid and localized cellular
      responses. Given the role of PG in supporting thymic T cell development, we
      investigated the expression of the PG synthases, also known as cyclooxygenases
      (COX)-1 and -2, in the biosynthesis of PGs in thymic stromal cell lines. The
      predominant isozyme expressed in cortical thymic epithelial cells was COX-1,
      while COX-2 predominated in the medulla. IFN-gamma up-regulated expression and
      activity of COX-2 in medullary cells, in which COX-2 was expressed
      constitutively. In contrast, IFN-gamma down-regulated COX-1 activity, but not
      expression, in cortical cells. Stromal cells support T cell development in the
      thymus, although the mediators of this effect are unknown. Selective inhibition
      of COX-2, but not COX-1, blocked the adhesion of CD4+CD8+ and CD4+CD8- thymocytes
      to medullary cell lines. No effect of the inhibitors was observed on the
      interactions of thymocytes with cortical epithelial lines. These data further
      support the differential regulation of COX-1 and COX-2 expression and function in
      thymic stromal cells. PGs produced by COX-2 in the medullary thymic stroma may
      regulate the development of thymocytes by modulating their interaction with
      stromal cells.

PMID- 10201999
TI  - TNF receptor 1-dependent beta cell toxicity as an effector pathway in autoimmune
      diabetes.
AB  - Autoimmune diabetes is characterized by a chronic progressive inflammatory
      autoimmune reaction that ultimately causes the selective elimination of
      pancreatic beta cells. To address the question of whether the cell death-inducing
      cytokines TNF and lymphotoxin alpha are involved in this process, we generated
      nonobese diabetic (NOD) mice that are deficient for TNF receptor 1 (TNFR1 or
      TNFRp55). Insulitis developed in these mice similarly to that in normal control
      NOD mice, but progression to diabetes was completely abrogated. Since this was
      probably due to the complex immunomodulatory effects of TNF and lymphotoxin alpha
      signaled via TNFR1 on lymphohemopoietic cells, adoptive transfer experiments with
      spleen cells from diabetic NOD mice were conducted. It was found that the absence
      of TNFR1 in recipients delayed diabetes induced by normal control and precluded
      diabetes induced by perforin-deficient spleen cells. In a CD8+ T cell-mediated
      model of diabetes, however, diabetes induced by adoptive transfer of TCR
      transgenic lymphocytic choriomeningitis virus glycoprotein-specific CD8+ T cells
      was not delayed by the absence of TNFR1 in recipient mice. Together with the
      described expression patterns of perforin and TNF in the mononuclear islet
      infiltrates of NOD mice, these results indicate that two diabetogenic effector
      mechanisms are delivered by distinct cell populations: CD8+ T cells lyse beta
      cells via perforin-dependent cytotoxicity, whereas CD4+ T cells, macrophages, and
      dendritic cells contribute to diabetes development via TNFR1-dependent beta cell
      toxicity.

PMID- 10202001
TI  - Two mechanisms for the non-MHC-linked resistance to spontaneous autoimmunity.
AB  - Genetic susceptibility and resistance to most autoimmune disorders are associated
      with highly polymorphic genes of the MHC and with non-MHC-linked polygenic
      modifiers. It is known that non-MHC-linked polymorphisms can override or enhance
      the susceptibility to an autoimmune disease provided by pathogenic MHC genes, but
      the mechanisms remain elusive. In this study, we have followed the fate of two
      highly diabetogenic beta cell-specific T cell receptors (Kd and I-Ag7 restricted,
      respectively) in NOR/Lt mice, which are resistant to autoimmune diabetes despite
      expressing two copies of the diabetogenic MHC haplotype H-2g7. We show that at
      least two mechanisms of non-MHC-linked control of pathogenic T cells operate in
      these mice. One segregates as a recessive trait and is associated with a
      reduction in the peripheral frequency of diabetogenic CD8+ (but not CD4+) T
      cells. The other segregates as a dominant trait and is mediated by IL-4- and TGF
      beta1-independent immune suppressive functions provided by lymphocytes that
      target diabetogenic CD4+ and CD8+ T cells, without causing their deletion,
      anergy, immune deviation, or ignorance. These results provide explanations as to
      how non-MHC-linked polymorphisms can override the susceptibility to an autoimmune
      disease provided by pathogenic MHC haplotypes, and demonstrate that protective
      non-MHC-linked genes may selectively target specific lymphoid cell types in
      cellularly complex autoimmune responses.

PMID- 10202000
TI  - Type 1 and type 2 cytokine regulation of macrophage endocytosis: differential
      activation by IL-4/IL-13 as opposed to IFN-gamma or IL-10.
AB  - Cytokine regulation of endocytic activity in primary human macrophages was
      studied to define ultrastructural changes and mechanisms of pinocytic regulation
      associated with cytokines secreted by activated T cells. The effects of IFN-gamma
      (type 1) and IL-4/IL-13 and IL-10 (type 2) cytokines on fluid phase and mannose
      receptor-mediated endocytosis were assessed by horseradish peroxidase and
      colloidal gold-BSA uptake and computer-assisted morphometric analysis. IL-4 and
      IL-13 enhanced fluid phase pinocytosis and mannose receptor-mediated uptake by
      activation of phosphatidylinositol 3-kinase. Inhibition of actin assembly showed
      that both cytokines exerted actin-dependent and -independent effects.
      Ultrastructurally, IL-4 and IL-13 increased tubular vesicle formation underneath
      the plasma membrane and at pericentriolar sites, concurrent with decreased
      particle sorting to lysosomes. By contrast, IL-10 or IFN-gamma decreased both
      fluid phase pinocytosis and mannose receptor-mediated uptake. IFN-gamma
      stimulated increased particle sorting to perinuclear lysosomes, while IL-10
      decreased this activity. In summary, our data document differential effects on
      macrophage endocytic functions by type 1 or type 2 cytokines associated with
      induction and effector pathways in immunity.

PMID- 10202002
TI  - Autoantigen-independent deletion of diabetogenic CD4+ thymocytes by protective
      MHC class II molecules.
AB  - Some MHC class II genes provide dominant resistance to certain autoimmune
      diseases via mechanisms that remain unclear. We have shown that thymocytes
      bearing a highly diabetogenic, I-Ag7-restricted beta-cell-reactive TCR (4.1-TCR)
      undergo negative selection in diabetes-resistant H-2g7/x mice by engaging several
      different antidiabetogenic MHC class II molecules on thymic (but not peripheral)
      hemopoietic cells, independently of endogenous superantigens. Here we have
      investigated 1) whether this TCR can also engage protective MHC class II
      molecules (I-Ab) on cortical thymic epithelial cells in the absence of
      diabetogenic (I-Ag7) molecules, and 2) whether deletion of 4.1-CD4+ thymocytes in
      I-Ab-expressing mice might result from the ability of I-Ab molecules to present
      the target beta-cell autoantigen of the 4.1-TCR. We show that, unlike I-Ag7
      molecules, I-Ab molecules can restrict neither the positive selection of 4.1-CD4+
      thymocytes in the thymic cortex nor the presentation of their target autoantigen
      in the periphery. Deletion of 4.1-CD4+ thymocytes by I-Ab molecules in the thymic
      medulla, however, is a peptide-specific process, since it can be triggered by
      hemopoietic cells expressing heterogeneous peptide/I-Ab complexes, but not by
      hemopoietic cells expressing single peptide/I-Ab complexes. Thus, unlike MHC
      autoreactive or alloreactive TCRs, which can engage deleting MHC molecules in the
      thymic cortex, thymic medulla, and peripheral APCs, the 4.1-TCR can only engage
      deleting MHC molecules (I-Ab) in the thymic medulla. We therefore conclude that
      this form of MHC-induced protection from diabetes is based on the presentation of
      an anatomically restricted, nonautoantigenic peptide to highly diabetogenic
      thymocytes.

PMID- 10202003
TI  - Complex conserved organization of the mammalian leukemia inhibitory factor gene:
      regulated expression of intracellular and extracellular cytokines.
AB  - Leukemia inhibitory factor (LIF) is a member of the IL-6 family of pleiotropic
      cytokines, which are extensively involved in modulating hematopoiesis and
      immunity. We have undertaken a detailed analysis of LIF genomic organization and
      gene transcription and investigated the proteins expressed from alternate
      transcripts. Previously unidentified LIF transcripts, containing alternate first
      exons spliced onto common second and third exons, were cloned from murine
      embryonic stem cells, human embryonal carcinoma cells, and primary porcine
      fibroblasts. Based on sequence homology and position within the genomic sequence,
      this confirmed the existence of the LIF-M transcript in species other than the
      mouse and identified a new class of transcript, designated LIF-T. Thus, a complex
      genomic organization of the LIF gene, conserved among eutherian mammals, results
      in the expression of three LIF transcripts (LIF-D, LIF-M, and LIF-T)
      differentially expressed from alternate promoters. The first exon of the LIF-T
      transcript contained no in-frame AUG, causing translation to initiate downstream
      of the secretory signal sequence at the first AUG in exon two, producing a
      truncated LIF protein that was localized within the cell. Enforced secretion of
      this protein demonstrated that it could act as a LIF receptor agonist. Regulated
      expression of biologically active intracellular and extracellular LIF cytokine
      could thus provide alternate mechanisms for the modulation of hematopoiesis and
      immune system function.

PMID- 10202004
TI  - Dramatic influence of V beta gene polymorphism on an antigen-specific CD8+ T cell
      response in vivo.
AB  - According to recent crystallographic studies, the TCR-alpha beta contacts MHC
      class I-bound antigenic peptides via the polymorphic V gene-encoded
      complementarity-determining region 1 beta (CDR1 beta) and the hypervariable (D)J
      encoded CDR3 beta and CDR3 alpha domains. To evaluate directly the relative
      importance of CDR1 beta polymorphism on the fine specificity of T cell responses
      in vivo, we have taken advantage of congenic V beta a and V beta b mouse strains
      that differ by a CDR1 polymorphism in the V beta 10 gene segment. The V beta 10
      restricted CD8+ T cell response to a defined immunodominant epitope was
      dramatically reduced in V beta a compared with V beta b mice, as measured either
      by the expansion of V beta 10+ cells or by the binding of MHC-peptide tetramers.
      These data indicate that V beta polymorphism has an important impact on TCR
      ligand binding in vivo, presumably by modifying the affinity of CDR1 beta-peptide
      interactions.

PMID- 10202005
TI  - Role of peptide backbone in T cell recognition.
AB  - T cells recognize self and nonself peptides presented by molecules of the MHC.
      Amino acid substitutions in the antigenic peptide showed that T cell specificity
      is highly degenerate. Recently, determination of the crystal structure of several
      TCR/MHC-peptide complexes suggested that the peptide backbone may significantly
      contribute to the interaction with the TCR. To directly investigate the role of
      the peptide backbone in T cell recognition, we performed a methylene-amino scan
      on the backbone of an antigenic peptide and measured the capacity of such
      pseudopeptides to bind their cognate MHC molecule, to sensitize target cells for
      T cell lysis, and to stimulate IL-2 secretion by two T cell hybridomas. For one
      of these pseudopeptides, we prepared fluorescent tetramers of MHC molecules and
      compared the staining of two T cell hybridomas. Our results demonstrate that the
      peptide backbone has an important contribution to TCR binding and suggest that
      some interactions between the peptide backbone and the TCR may be partially
      conserved. We discuss this finding in the perspective of TCR plasticity and T
      cell function.

PMID- 10202006
TI  - DNA binding by the VH domain of anti-Z-DNA antibody and its modulation by
      association of the VL domain.
AB  - mAb Z22 is a highly selective IgG anti-Z-DNA Ab from an immunized C57BL/6 mouse.
      Previous studies showed that heavy chain CDR3 amino acids are critical for Z-DNA
      binding by the single chain variable fragment (scFv) comprising both V region
      heavy chain (VH) and V region light chain (VL) of mAb Z22 and that the VH domain
      alone binds Z-DNA with an affinity similar to that of whole variable fragment
      (Fv). To determine whether Z-DNA binding by VH alone and by Fv involves identical
      complementarity determining region residues, we tested effects of single or
      multiple amino acid substitutions in recombinant VH, scFv, and associated VH-VL
      heterodimers. Each recombinant product was a fusion protein with a B domain of
      Staphylococcal protein A (SPA). Z22VH-SPA alone was not highly selective; it
      bound strongly to other polynucleotides, particularly polypyrimidines, and ssDNA
      as well as to Z-DNA. In contrast, scFv-SPA or associated VH-VL dimers bound only
      to Z-DNA. VL-SPA domains bound weakly to Z-DNA; SPA alone did not bind.
      Introduction of multiple substitutions revealed that the third complementarity
      determining region of the heavy chain (CDR3H) was critical for both VH and scFv
      binding to Z-DNA. However, single substitutions that eliminated or markedly
      reduced Z-DNA binding by scFv instead caused a modest increase or no reduction in
      binding by VH alone. Association of VH-SPA with Z22VL-SPA restored both the
      effects of single substitutions and Z-DNA selectivity seen with Fv and intact Ab.
      Polypyrimidine and ssDNA binding by the isolated VH domain of immunization
      induced anti-Z-DNA Ab resembles the activity of natural autoantibodies and
      suggests that VH-dependent binding to a ligand mimicked by polypyrimidines may
      play a role in B cell selection before immunization with Z-DNA.

PMID- 10202007
TI  - Sodium dodecyl sulfate-resistant HLA-DR "superdimer" bands are in some cases
      class II heterodimers bound to antibody.
AB  - The detection of dimers of dimers in MHC class II crystals has excited
      speculation about their possible functions in T cell Ag recognition. Biochemical
      evidence for the existence of DR superdimers falls short of proof and is
      controversial. To monitor B lymphoma cells for high m.w. complexes of HLA-DR
      molecules, membrane preparations and cell lysates were screened by one- and two
      dimensional Western blotting. Under these conditions, in which DRalpha beta
      heterodimers were readily detected, no DR complexes with an (alpha beta)2-chain
      composition could be identified. Two mAbs (L243 and D1-12) immunoprecipitated
      high m.w. DR complexes suspected to be superdimers. However, biochemical analysis
      revealed that, rather than superdimers, these were SDS-stable complexes of DR in
      combination with the Abs. Thus, previous observations of HLA-DR superdimer bands
      may also reflect complexes of DR molecules with bound Ab.

PMID- 10202008
TI  - TAP association influences the conformation of nascent MHC class I molecules.
AB  - The influence of TAP-MHC class I interactions on peptide binding to the class I
      heavy chain is assessed during TAP-dependent assembly using Kb-specific Abs that
      recognize conformational changes induced by assembly with beta2-microglobulin
      (beta2m) and by peptide binding. A significant portion (45%) of Kb molecules in
      TAP+, RMA-derived microsomes are associated with the TAP complex as measured by
      coimmunoisolation of Kb using anti-TAP1 Abs, while only 20% of the Kb heavy chain
      molecules are isolated as Kbbeta2m complexes with the alpha-Kb-specific Abs, Y-3
      or K-10-56. The amount of Kb isolated with Y-3 and K-10-56 increases in
      proportion to transport and binding of peptide to the Kb molecules within the RMA
      microsomes. In contrast, less than 5% of the Kb within TAP2-RMA-S microsomes
      associated with the remaining TAP1 subunit. However, greater than 60% of Kb heavy
      chain is isolated as K-10-56- and Y-3-reactive Kbbeta2m complexes. We propose
      that a TAP-MHC class I interaction serves to stabilize the MHC class I:beta2m
      complex in an immature conformation (Y-3 and K-10-56 nonreactive) prior to high
      affinity peptide binding, preventing the export of class I molecules complexed
      with low affinity peptide ligands from the ER.

PMID- 10202009
TI  - Vasoactive intestinal peptide and pituitary adenylate cyclase-activating
      polypeptide prevent inducible nitric oxide synthase transcription in macrophages
      by inhibiting NF-kappa B and IFN regulatory factor 1 activation.
AB  - High-output nitric oxide (NO) production from activated macrophages, resulting
      from the induction of inducible NO synthase (iNOS) expression, represents a major
      mechanism for macrophage cytotoxicity against pathogens. However, despite its
      beneficial role in host defense, sustained high-output NO production was also
      implicated in a variety of acute inflammatory diseases and autoimmune diseases.
      Therefore, the down-regulation of iNOS expression during an inflammatory process
      plays a significant physiological role. This study examines the role of two
      immunomodulatory neuropeptides, the vasoactive intestinal peptide (VIP) and the
      pituitary adenylate cyclase-activating polypeptide (PACAP), on NO production by
      LPS-, IFN-gamma-, and LPS/IFN-gamma-stimulated peritoneal macrophages and the Raw
      264.7 cell line. Both VIP and PACAP inhibit NO production in a dose- and time
      dependent manner by reducing iNOS expression at protein and mRNA level. VPAC1,
      the type 1 VIP receptor, which is constitutively expressed in macrophages, and to
      a lesser degree VPAC2, the type 2 VIP receptor, which is induced upon macrophage
      activation, mediate the effect of VIP/PACAP. VIP/PACAP inhibit iNOS expression
      and activity both in vivo and in vitro. Two transduction pathways appear to be
      involved, a cAMP-dependent pathway that preferentially inhibits IFN regulatory
      factor-1 transactivation and a cAMP-independent pathway that blocks NF-kappa B
      binding to the iNOS promoter. The down-regulation of iNOS expression, together
      with previously reported inhibitory effects on the production of the
      proinflammatory cytokines IL-6, TNF-alpha, and IL-12, and the stimulation of the
      anti-inflammatory IL-10, define VIP and PACAP as "macrophage deactivating
      factors" with significant physiological relevance.

PMID- 10202011
TI  - Diesel exhaust particles induce NF-kappa B activation in human bronchial
      epithelial cells in vitro: importance in cytokine transcription.
AB  - Fine particles derived from diesel engines (diesel exhaust particles, DEP) have
      attracted attention, since their density in industrial countries seems related to
      the increased prevalence of pulmonary diseases. Previous studies have suggested
      that DEP have a potential to directly activate airway epithelial cells to produce
      and release inflammatory cytokines and mediators, and thus facilitate
      inflammatory responses in the lung. To elucidate the molecular mechanisms of
      their action, we studied here IL-8 gene expression, one of the important
      cytokines in inflammatory responses, by Northern blot analysis and run-on
      transcription assay. Suspended DEP (1-50 microgram/ml) increased the steady state
      levels of IL-8 mRNA, which was suggested to be largely due to increased
      transcriptional rates. Electrophoretic mobility shift assay demonstrated that DEP
      induced increased binding to the specific motif of NF-kappa B, but not of
      transcription factor AP-1. The luciferase reporter gene assay using wild-type and
      mutated NF-kappa B-binding sequences showed that DEP-induced NF-kappa B
      activation was involved in IL-8 transcription. Finally, both N-acetylcysteine and
      pyrrolidine dithiocarbamate attenuated the action of DEP on IL-8 mRNA expression,
      suggesting that oxidant-mediated pathway might be involved in its processes.
      These results suggested that DEP activate NF-kappa B, which might be an important
      mechanism of its potential to increase the expression of inflammatory cytokines
      in vitro.

PMID- 10202010
TI  - Binding motifs of copolymer 1 to multiple sclerosis- and rheumatoid arthritis
      associated HLA-DR molecules.
AB  - Copolymer 1 (Cop 1, poly (Y, E, A, K)) is a random synthetic amino acid copolymer
      effective in the treatment of relapsing forms of multiple sclerosis (MS). Cop 1
      binds promiscuously, with high affinity and in a peptide-specific manner to
      purified MS-associated HLA-DR2 (DRB1*1501) and rheumatoid arthritis-associated
      HLA-DR1 (DRB1*0101) or HLA-DR4 (DRB1*0401) molecules. In the present work at
      least 95% of added Cop 1 could be bound to recombinant "empty" HLA-DR1 and -DR4,
      and 80% could be bound to HLA-DR2 proteins. Amino acid composition, HPLC
      profiles, and sequencing patterns of Cop 1 eluted by acid extraction from HLA-DR
      molecules were similar to those of the unseparated Cop 1. Protruding N-terminal
      ends of Cop 1 bound to HLA-DR1, -DR2, or -DR4 molecules were then treated with
      aminopeptidase I, followed by elution, HPLC, and pool sequencing. In contrast to
      untreated or unbound Cop 1, this material exhibited distinct motifs at some
      positions with increases in levels of E at the first and second cycles, of K at
      the second and third cycles, and of Y (presumably at P1 of the bound peptide) at
      the third to fifth cycles, regardless of the HLA-DR molecule employed. No
      preference was seen at the following cycles that were mainly A. These first
      pooled HLA-DR binding epitopes provide clues to the components of Cop 1 that are
      biologically active in suppressing MS and possibly rheumatoid arthritis.

PMID- 10202012
TI  - Specific proteolytic cleavages limit the diversity of the pool of peptides
      available to MHC class I molecules in living cells.
AB  - MHC class I molecules display peptides selected from a poorly characterized pool
      of peptides available in the endoplasmic reticulum. We analyzed the diversity of
      peptides available to MHC class I molecules by monitoring the generation of an
      OVA-derived octapeptide, OVA257-264 (SL8), and its C-terminally extended analog,
      SL8-I. The poorly antigenic SL8-I could be detected in cell extracts only after
      its conversion to the readily detectable SL8 with carboxypeptidase Y. Analysis of
      extracts from cells expressing the minimal precursor Met-SL8-I by this method
      revealed the presence of SL8/Kb and the extended SL8-I/Kb complexes, indicating
      that the peptide pool contained both peptides. In contrast, cells expressing full
      length OVA generated only the SL8/Kb complex, demonstrating that the peptide pool
      generated from the full length precursor contained only a subset of potential MHC
      binding peptides. Deletion analysis revealed that SL8-I was generated only from
      precursors lacking additional C-terminal flanking residues, suggesting that the
      generation of the C terminus of the SL8 peptide involves a specific endopeptidase
      cleavage. To investigate the protease responsible for this cleavage, we tested
      the effect of different protease inhibitors on the generation of the SL8 and SL8
      I peptides. Only the proteasome inhibitors blocked generation of SL8, but not SL8
      I. These findings demonstrate that the specificities of the proteases in the Ag
      processing pathway, which include but are not limited to the proteasome, limit
      the diversity of peptides available for binding by MHC class I molecules in the
      endoplasmic reticulum.

PMID- 10202013
TI  - An 11-amino acid sequence in the cytoplasmic domain of CD40 is sufficient for
      activation of c-Jun N-terminal kinase, activation of MAPKAP kinase-2,
      phosphorylation of I kappa B alpha, and protection of WEHI-231 cells from anti
      IgM-induced growth arrest.
AB  - We have previously shown that CD40 causes strong activation of the c-Jun N
      terminal kinase (JNK), the p38 mitogen-activated protein kinases (MAPK) and
      MAPKAP kinase-2, a downstream target of p38 MAPK. To identify signaling motifs in
      the CD40 cytoplasmic domain that are responsible for activation of these kinases,
      we have created a set of 11 chimeric receptors consisting of the extracellular
      and transmembrane domains of CD8 fused to portions of the murine CD40 cytoplasmic
      domain. These chimeric receptors were expressed in WEHI-231 B lymphoma cells. We
      found that amino acids 35-45 of the CD40 cytoplasmic domain constitute an
      independent signaling motif that is sufficient for activation of the JNK and p38
      MAPK pathways, as well as for induction of I kappa B alpha phosphorylation and
      degradation. Amino acids 35-45 were also sufficient to protect WEHI-231 cells
      from anti-IgM-induced growth arrest. This is the same region of CD40 required for
      binding the TNF receptor-associated factor-2 (TRAF2), TRAF3, and TRAF5 adapter
      proteins. These data support the idea that one or more of these TRAF proteins
      couple CD40 to the kinase cascades that activate NF-kappa B, JNK, and p38 MAPK.

PMID- 10202014
TI  - IFN-gamma regulation of the type IV class II transactivator promoter in
      astrocytes.
AB  - The transcriptional activation of class II MHC genes requires the class II
      transactivator (CIITA) protein, a regulator that is essential for both
      constitutive and IFN-gamma-inducible class II MHC expression. The CIITA gene is
      controlled by multiple independent promoters; two promoters direct constitutive
      expression, while another, the type IV CIITA promoter, mediates IFN-gamma-induced
      expression. We investigated the molecular regulation of IFN-gamma-induced type IV
      CIITA promoter activity in astrocytes. IFN-gamma inducibility of the type IV
      CIITA promoter is dependent on three cis-acting elements contained within a 154
      bp fragment of the promoter; the proximal IFN-gamma activation sequence (GAS)
      element, the E box, and the proximal IFN regulatory factor (IRF) element. Two IFN
      gamma-activated transcription factors, STAT-1alpha and IRF-1, bind the proximal
      GAS and IRF elements, respectively. The E box binds upstream stimulating factor-1
      (USF-1), a constitutively expressed transcription factor. Furthermore, STAT
      1alpha binding to the proximal GAS element is dependent on the binding of USF-1
      to the adjacent E box. Functionally, the proximal IRF element is essential for
      IFN-gamma induction of type IV CIITA promoter activity, while the proximal GAS
      and E box elements contribute to the IFN-gamma inducibility of this promoter. In
      astrocytes, TNF-alpha enhances IFN-gamma-induced class II MHC transcription. Our
      results demonstrate that TNF-alpha does not enhance IFN-gamma-induced
      transcriptional activation of the type IV CIITA promoter, indicating that the
      enhancing effect of TNF-alpha is mediated downstream of CIITA transcription.
      These results define the molecular basis of IFN-gamma activation of the type IV
      CIITA promoter in astrocytes.

PMID- 10202015
TI  - MHC-restricted, glycopeptide-specific T cells show specificity for both
      carbohydrate and peptide residues.
AB  - We examined the antigenic specificity of two T cell hybridomas elicited against
      the disaccharide galabiose attached to the fifth residue of the I-Ak binding
      peptide 52-61 of lysozyme. By making changes in the saccharide molecule and in
      the peptide, we conclude that the outer galactose residue of the galabiose moiety
      is directly recognized by the T cells together with the exposed side chains of
      the peptide. The overall spatial display of this galactose moiety on the 52-61
      peptide is likewise important.

PMID- 10202016
TI  - A new member of the Ig superfamily and a V-ATPase G subunit are among the
      predicted products of novel genes close to the TNF locus in the human MHC.
AB  - It is becoming increasingly apparent that many of the genes in the class III
      region of the human MHC encode proteins involved in the immune and inflammatory
      responses. Furthermore, genetic studies have indicated that genes within the
      class III region, particularly the telomeric segment containing the TNF gene,
      could contribute to susceptibility to diseases of immune-related etiology. We
      have sequenced an 82-kb segment of DNA around the TNF gene to identify candidate
      disease susceptibility genes in this region. The 10 known genes in this region
      have been precisely positioned with the order allograft inflammatory factor 1,
      G1, 1C7, leukocyte-specific transcript 1 (B144), lymphotoxin B, TNF, lymphotoxin
      A, NB6, IKBL, BAT1 (centromere to telomere), and their genomic structures have
      been defined. Comparison of the G1 genomic region with previously described cDNA
      and genomic sequences, together with the results of reverse transcriptase-PCR,
      indicates that three alternative transcripts, G1, allograft inflammatory factor
      1, and IFN-gamma-responsive transcript, are all derived from this gene. The
      completion of the sequence of 1C7 (D6S2570) has revealed that this gene encodes a
      putative novel member of the Ig superfamily. A number of alternatively spliced
      transcripts of 1C7 were identified by reverse transcriptase-PCR, all of which are
      expressed in immune-related cell lines. Alternative splicing within the Ig domain
      encoding region was seen to result in possible set switching between an IgV
      domain and an IgC2 domain. Lastly, a previously unidentified gene, homologous to
      a number of V-ATPase G subunits, has been located 1 kb telomeric of IKBL.

PMID- 10202017
TI  - Two independent calcineurin-binding regions in the N-terminal domain of murine NF
      ATx1 recruit calcineurin to murine NF-ATx1.
AB  - Intracellular calcium regulates events controlling nuclear translocation of
      nuclear factor of activated T cells (NF-AT). Calcium-dependent phosphatase
      calcineurin (CN) plays a central role in this process. Structural and functional
      analyses of the N-terminal domain of murine NF-ATx1, a member of the NF-AT
      family, have defined two distinct CN binding regions (CNBRs), CNBR1 and CNBR2,
      which are located in the region preceding the SP boxes of serine/proline-rich
      sequences and the region between the SP boxes and Rel similarity domain,
      respectively. The binding of murine NF-ATx1 (mNF-ATx1) to CN was abolished by
      deletion of these two regions, yet was unaffected by the individual deletion. In
      contrast, the nuclear translocation of mNF-ATx1 was much reduced when only CNBR2
      was removed. Luciferase assay revealed that both regions are required for mNF
      ATx1-dependent activation of the murine IL-2 promoter. Most importantly,
      recombinant CNBR2 bound CN with a higher affinity, and when expressed in Jurkat
      cells, it functioned as a dominant negative mutant that prevented the
      transcription driven by exogenous mNF-ATx1, probably by interfering with the
      function of CN. We propose that activation of mNF-ATx1 can be modulated through
      two distinct CN target regions. Our findings provide a new opportunity for
      pharmacological intervention with Ca2+-dependent signaling events.

PMID- 10202018
TI  - The origin and function of soluble CD14 in experimental bacterial meningitis.
AB  - Murine experimental meningitis models induced by either Escherichia coli LPS,
      live Streptococcus pneumoniae, or Listeria monocytogenes were used to study the
      origin and potential function of soluble CD14 (sCD14) in the brain during
      bacterial meningitis. Whereas intracerebral infection caused only a minor and/or
      transient increase of sCD14 levels in the serum, dramatically elevated
      concentrations of sCD14 were detected in the cerebrospinal fluid. Reverse
      transcriptase PCR and FACS analysis of the leukocytes invading the subarachnoid
      compartment revealed an active amplification of CD14 transcription and
      concomitant surface expression. These findings were confirmed by in situ
      hybridization and immunohistochemical analysis. In contrast, parenchymal
      astrocytes and microglial cells were shown not to significantly contribute to the
      elevated levels of sCD14. Simultaneous intracerebral inoculation of rsCD14 and S.
      pneumoniae resulted in a markedly increased local cytokine response. Taken
      together, these data provide the first evidence that sCD14 can act as an
      inflammatory co-ligand in vivo. Thus, during bacterial meningitis, sCD14 is
      massively released by intrathecal leukocytes, and the sCD14 found in the
      cerebrospinal fluid can play an important role in the pathogenesis of this
      disease.

PMID- 10202020
TI  - Enhancement of the Listeria monocytogenes p60-specific CD4 and CD8 T cell memory
      by nonpathogenic Listeria innocua.
AB  - The contact of T cells to cross-reactive antigenic determinants expressed by
      nonpathogenic environmental micro-organisms may contribute to the induction or
      maintenance of T cell memory. This hypothesis was evaluated in the model of
      murine Listeria monocytogenes infection. The influence of nonpathogenic L.
      innocua on the L. monocytogenes p60-specific T cell response was analyzed. We
      show that some CD4 T cell clones raised against purified p60 from L.
      monocytogenes cross-react with p60 purified from L. innocua. The L. monocytogenes
      p60-specific CD4 T cell clone 1A recognized the corresponding L. innocua p60
      peptide QAAKPAPAPSTN, which differs only in the first amino acid residue. In
      vitro experiments revealed that after L. monocytogenes infection of APCs, MHC
      class I-restricted presentation of p60 occurs, while MHC class II-restricted p60
      presentation is inhibited. L. innocua-infected cells presented p60 more weakly
      but equally well in the context of both MHC class I and MHC class II. In contrast
      to these in vitro experiments the infection of mice with L. monocytogenes induced
      a strong p60-specific CD4 and CD8 T cell response, while L. innocua infection
      failed to induce p60-specific T cells. L. innocua booster infection, however,
      expanded p60-specific memory T cells induced by previous L. monocytogenes
      infection. In conclusion, these findings suggest that infection with a frequently
      occurring environmental bacterium such as L. innocua, which is nonpathogenic and
      not adapted to intracellular replication, can contribute to the maintenance of
      memory T cells specific for a related intracellular pathogen.

PMID- 10202019
TI  - Actinobacillus actinomycetemcomitans immunosuppressive protein is a member of the
      family of cytolethal distending toxins capable of causing a G2 arrest in human T
      cells.
AB  - We have previously shown that Actinobacillus actinomycetecomitans produces an
      immunosuppressive factor (ISF) capable of impairing human lymphocyte function by
      perturbing cell cycle progression. We now report that ISF is the product of the
      cdtB gene, one of three genes encoding the family of cytolethal distending toxins
      (Cdt). The ISF polypeptide exhibits >/=95% identity with Hemophilus ducreyi CdtB
      protein and </=60% homology with Escherichia coli or Campylobacter jejuni CdtB.
      Pretreatment of PHA-activated lymphocytes with 5-25 ng ISF results in G2 arrest
      of CD4+ and CD8+ T cells. Similarly, treatment of HeLa cells results in G2 arrest
      and cell elongation and distension. However, lymphocytes are at least 5 times
      more sensitive to ISF than HeLa cells and do not undergo the elongation and
      distension that characterizes interactions of Cdts with cell lines. ISF-treated
      lymphocytes express normal cyclin A and B1 levels, but contain reduced levels of
      cell cycle-dependent kinase-1 (Cdk1). Additionally, the majority of Cdk1 is in
      the hyperphosphorylated, inactive, form. In contrast, PHA-induced G2 cells
      contain elevated levels of the hypophosphorylated, active Cdk1. Failure of ISF
      treated cells to dephosphorylate Cdk1 is not associated with decreased
      availability of Cdc25. These studies suggest that the CdtB protein alone is
      capable of inducing G2 arrest in lymphocytes and cell cycle arrest, elongation,
      and distension of HeLa cells. Our studies also suggest that lymphocytes may be
      primary targets for A. actinomycetemcomitans CdtB (ISF) and possibly for other
      Cdt family members as well. Thus, Cdts may function to impair host immunity and
      contribute to the pathogenesis of disease associated with Cdt-producing
      organisms.

PMID- 10202021
TI  - DNA vaccination against the idiotype of a murine B cell lymphoma: mechanism of
      tumor protection.
AB  - Several studies have shown that immunization with DNA, which encodes the
      idiotypic determinants of a B cell lymphoma, generates tumor-specific immunity.
      Although induction of antiidiotypic Abs has correlated with tumor protection, the
      effector mechanisms that contribute to tumor protection have not been clearly
      identified. This study evaluated the tumor protective effects of humoral and
      cellular immune mechanisms recruited by idiotype-directed DNA vaccines in the
      38C13 murine B cell lymphoma model. Antiidiotypic Abs induced by DNA vaccination
      supported in vitro complement-mediated cytotoxicity of tumor cells, and
      simultaneous transfer of tumor cells and hyperimmune sera protected naive animals
      against tumor growth. However, in vitro stimulation of immune splenocytes with
      tumor cells failed to induce idiotype-specific cytotoxicity, and following
      vaccination, depletion of CD4 or CD8 T cell subsets did not compromise
      protection. Furthermore, protection of naive recipients against tumor challenge
      could not be demonstrated either by a Winn assay approach or by adoptive transfer
      of spleen and lymph node cells. Thus, in this experimental model, current
      evidence suggests that the tumor-protective effects of DNA vaccination can be
      largely attributed to idiotype-specific humoral immunity.

PMID- 10202022
TI  - Persistent HIV-1-specific CTL clonal expansion despite high viral burden post in
      utero HIV-1 infection.
AB  - To address the issue of clonal exhaustion in humans, we monitored HLA class I
      restricted, epitope-specific CTL responses in an in utero HIV-1-infected infant
      from 3 mo through 5 years of age. Serial functional CTL precursor assays
      demonstrated persistent, vigorous, and broadly directed HIV-1 specific CTL
      activity with a dominant response against an epitope in HIV-1 Gag-p17 (SLYNTVATL,
      aa 77-85). A clonal CTL response directed against the immunodominant, HLA-A*0201
      restricted epitope was found to persist over the entire observation period, as
      shown by TCR analysis of cDNA libraries generated from PBMC. The analysis of
      autologous viral sequences did not reveal any escape mutations within the
      targeted epitope, and viral load measurement indicated ongoing viral replication.
      Furthermore, inhibition of viral replication assays indicated that the epitope
      was properly processed from autologous viral protein. These data demonstrate that
      persistent exposure to high levels of viral Ag does not necessarily lead to
      clonal exhaustion and that epitope-specific clonal CTL responses induced within
      the first weeks of life can persist for years without inducing detectable viral
      escape variants.

PMID- 10202023
TI  - CD14 plays no major role in shock induced by Staphylococcus aureus but down
      regulates TNF-alpha production.
AB  - Recent in vitro studies have suggested that CD14, a major receptor for LPS, may
      also be a receptor for cell wall components of Gram-positive bacteria and thus
      play a role in Gram-positive shock. To analyze the in vivo role of CD14 in
      responses to Gram-positive bacteria, CD14-deficient and control mice were
      injected with Staphylococcus aureus, and the effects on lethality, bacterial
      clearance, and production of cytokines were analyzed. Survival of CD14-deficient
      and control mice did not differ significantly after administration of various
      doses of either unencapsulated or encapsulated S. aureus; furthermore, mice in
      both groups displayed similar symptoms of shock. In addition, inflammatory
      cytokines such as TNF-alpha and IL-6 were readily detectable in the serum of CD14
      deficient mice injected with live or antibiotic-killed S. aureus. Surprisingly,
      the serum concentration of TNF-alpha in CD14-deficient mice was at least
      threefold higher than in control mice after injection of either unencapsulated or
      encapsulated S. aureus, suggesting that CD14 down-regulates TNF-alpha. A similar
      increase in serum TNF-alpha occurred when CD14-deficient animals were injected
      with gentamicin-killed bacteria even though no symptoms of shock were observed.
      These studies indicate that CD14, in contrast to its key function in responses to
      the Gram-negative bacterium, Escherichia coli 0111, does not play a prominent
      role in septic shock induced by S. aureus, and that the symptoms of S. aureus
      shock are not due solely to TNF-alpha.

PMID- 10202024
TI  - Human cytomegalovirus binding to human monocytes induces immunoregulatory gene
      expression.
AB  - To continue our investigation of the cellular events that occur following human
      CMV (HCMV) infection, we focused on the regulation of cellular activation
      following viral binding to human monocytes. First, we showed that viral binding
      induced a number of immunoregulatory genes (IL-1beta, A20, NF-kappaB-p105/p50,
      and IkappaBalpha) in unactivated monocytes and that neutralizing Abs to the major
      HCMV glycoproteins, gB (UL55) and gH (UL75), inhibited the induction of these
      genes. Next, we demonstrated that these viral ligands directly up-regulated
      monocyte gene expression upon their binding to their appropriate cellular
      receptors. We then investigated if HCMV binding also resulted in the translation
      and secretion of cytokines. Our results showed that HCMV binding to monocytes
      resulted in the production and release of IL-1beta protein. Because these induced
      gene products have NF-kappaB sites in their promoter regions, we next examined
      whether there was an up-regulation of nuclear NF-kappaB levels. These experiments
      showed that, in fact, NF-kappaB was translocated to the nucleus following viral
      binding or purified viral ligand binding. Changes in IkappaBalpha levels
      correlated with the changes in NF-kappaB translocation. Lastly, we demonstrated
      that p38 kinase activity played a central role in IL-1beta production and that it
      was rapidly up-regulated following infection. These results support our
      hypothesis that HCMV initiates a signal transduction pathway that leads to
      monocyte activation and pinpoints a potential mechanism whereby HCMV infection of
      monocytes can result in profound pathogenesis, especially in chronic inflammatory
      type conditions.

PMID- 10202025
TI  - Host B7-1 and B7-2 costimulatory molecules contribute to the eradication of B7-1
      transfected P815 tumor cells via a CD8+ T cell-dependent mechanism.
AB  - B7-1 (CD80)-transfected P815 tumor cells were previously shown to elicit tumor
      eradicating immunity that leads to the regression of B7-1+ P815 tumors after
      transient growth in normal syngeneic (DBA/2) mice. Here, we show that not only
      the B7-1 molecule but also the B7-2 (CD86) molecule contributed to the
      eradication of B7-1+ P815 tumors. The B7-1 molecule that contributed to the
      eradication of B7-1+ P815 tumors was expressed not only on the tumor cells but
      also on host APCs, including MAC-1+ cells. The B7-2 molecule that contributed to
      the eradication of B7-1+ P815 tumors was expressed only on host APCs, such as
      B220+ cells, and not on the tumor cells. In spite of the fact that B7-expressing
      host APCs contributed to the eradication of B7-1+ P815 tumors, only CD8+ T cells
      without help from CD4+ T cells were important for tumor eradication. Taken
      together, these findings indicate that in addition to the ability of B7-1
      transfected tumor cells to stimulate CD8+ T cell-mediated tumor-eradicating
      immunity directly, such tumor cells can also stimulate CD8+ T cell-mediated tumor
      eradicating immunity indirectly as a result of cross-priming through B7
      expressing host APCs.

PMID- 10202026
TI  - Role of the C-C chemokine, TCA3, in the protective anticryptococcal cell-mediated
      immune response.
AB  - Activated T lymphocytes play a crucial role in orchestrating cellular
      infiltration during a cell-mediated immune (CMI) reaction. TCA3, a C-C chemokine,
      is produced by Ag-activated T cells and is chemotactic for neutrophils and
      macrophages, two cell types in a murine CMI reaction. Using a gelatin sponge
      model for delayed-type hypersensitivity (DTH), we show that TCA3 is a component
      of the expression phase of an anticryptococcal CMI response in mice. TCA3 mRNA
      levels are augmented in anticryptococcal DTH reactions at the same time peak
      influxes of neutrophils and lymphocytes are observed. Neutralization of TCA3 in
      immunized mice results in reduced numbers of neutrophils and lymphocytes at DTH
      reaction sites. However, when rTCA3 is injected into sponges in naive mice, only
      neutrophils are attracted into the sponges, indicating TCA3 is chemotactic for
      neutrophils, but not lymphocytes. We show that TCA3 is indirectly attracting
      lymphocytes into DTH-reactive sponges by affecting at least one other chemokine
      that is chemotactic for lymphocytes. Of the two lymphocyte-attracting chemokines
      assessed, monocyte-chemotactic protein-1 and macrophage-inflammatory protein
      1alpha (MIP-1alpha), only MIP-1alpha was reduced when TCA3 was neutralized,
      indicating that TCA3 affects the levels of MIP-1alpha, which attracts lymphocytes
      into the sponges. TCA3 also plays a role in protection against Cryptococcus
      neoformans in the lungs and brains of infected mice, as evidenced by the fact
      that neutralization of TCA3 results in increased C. neoformans CFU in those two
      organs.

PMID- 10202027
TI  - Signal transduction pathways activated in endothelial cells following infection
      with Chlamydia pneumoniae.
AB  - Chlamydia pneumoniae is an important respiratory pathogen. Recently, its presence
      has been demonstrated in atherosclerotic lesions. In this study, we characterized
      C. pneumoniae-mediated activation of endothelial cells and demonstrated an
      enhanced expression of endothelial adhesion molecules followed by subsequent
      rolling, adhesion, and transmigration of leukocytes (monocytes, granulocytes).
      These effects were blocked by mAbs against endothelial and/or leukocyte adhesion
      molecules (beta1 and beta2 integrins). Additionally, activation of different
      signal transduction pathways in C. pneumoniae-infected endothelial cells was
      shown: protein tyrosine phosphorylation, up-regulation of phosphorylated p42/p44
      mitogen-activated protein kinase, and NF-kappaB activation/translocation occurred
      within 10-15 min. Increased mRNA and surface expression of E-selectin, ICAM-1,
      and VCAM-1 were noted within hours. Thus, C. pneumoniae triggers a cascade of
      events that could lead to endothelial activation, inflammation, and thrombosis,
      which in turn may result in or may promote atherosclerosis.

PMID- 10202028
TI  - A novel beta 1 integrin-dependent mechanism of leukocyte adherence to apoptotic
      cells.
AB  - Adherence of leukocytes to cells undergoing apoptosis has been reported to be
      dependent on a variety of recognition pathways. These include alpha V beta 3
      (CD51/CD61, vitronectin receptor), CD36 (thrombospondin receptor), macrophage
      class A scavenger receptor, phosphatidylserine translocated to the outer leaflet
      of apoptotic cell membranes, and CD14 (LPS-binding protein). We investigated the
      mechanism by which leukocytes adhere to apoptotic endothelial cells (EC).
      Peripheral blood mononuclear leukocytes and U937 monocytic cells adhered to human
      or bovine aortic EC induced to undergo apoptosis by withdrawal of growth factors,
      treatment with the promiscuous protein kinase inhibitor staurosporine, with the
      protein synthesis inhibitor and protein kinase activator anisomycin, or with the
      combination of cycloheximide and TNF-alpha. Expression of endothelial adherence
      molecules such as CD62E (E-selectin), CD54 (ICAM-1), and CD106 (VCAM-1) was not
      induced or increased by these treatments. A mAb to alpha V beta 3, exogenous
      thrombospondin, or blockade of phosphatidylserine by annexin V did not inhibit
      leukocyte adherence. Further, leukocyte binding to apoptotic EC was completely
      blocked by treatment of leukocytes but not EC with mAb to beta 1 integrin. These
      results define a novel pathway for the recognition of apoptotic cells.

PMID- 10202029
TI  - Extracellular acidification induces human neutrophil activation.
AB  - In the current work, we evaluated the effect of extracellular acidification on
      neutrophil physiology. Neutrophils suspended in bicarbonate-buffered RPMI 1640
      medium adjusted to acidic pH values (pH 6.5-7.0) underwent: 1) a rapid transient
      increase in intracellular free calcium concentration levels; 2) an increase in
      the forward light scattering properties; and 3) the up-regulation of surface
      expression of CD18. By contrast, extracellular acidosis was unable to induce
      neither the production of H2O2 nor the release of myeloperoxidase. Acidic
      extracellular pH also modulated the functional profile of neutrophils in response
      to conventional agonists such as FMLP, precipiting immune complexes, and
      opsonized zymosan. It was found that not only calcium mobilization, shape change
      response, and up-regulation of CD18 expression but also production of H2O2 and
      release of myeloperoxidase were markedly enhanced in neutrophils stimulated in
      acidic pH medium. Moreover, extracellular acidosis significantly delayed
      neutrophil apoptosis and concomitantly extended neutrophil functional lifespan.
      Extracellular acidification induced an immediate and abrupt fall in the
      intracellular pH, which persisted over the 240-s analyzed. A similar abrupt drop
      in the intracellular pH was detected in cells suspended in bicarbonate
      supplemented PBS but not in those suspended in bicarbonate-free PBS. A role for
      intracellular acidification in neutrophil activation is suggested by the fact
      that only neutrophils suspended in bicarbonate-buffered media (i.e., RPMI 1640
      and bicarbonate-supplemented PBS) underwent significant shape changes in response
      to extracellular acidification. Together, our results support the notion that
      extracellular acidosis may intensify acute inflammatory responses by inducing
      neutrophil activation as well as by delaying spontaneous apoptosis and extending
      neutrophil functional lifespan.

PMID- 10202030
TI  - Endotoxin-stimulated monocytes release multiple forms of IL-1 beta, including a
      proIL-1 beta form whose detection is affected by export.
AB  - The processing and release of 31-kDa proIL-1 beta to the mature 17-kDa form of IL
      1 beta are still poorly understood. To help elucidate the mechanisms involved in
      IL-1 beta processing and release, we measured IL-1 beta forms released from
      endotoxin-stimulated monocytes by immunoprecipitation of [35S]methionine-labeled
      protein, by Western blots, and by our recently developed ELISA specific for proIL
      1 beta. Our studies demonstrate that in addition to the 17-kDa mature IL-1 beta,
      IL-1 beta is also released as 31-, 28-, and 3-kDa molecules. The 31-kDa-released
      form of proIL-1 beta represented 20-40% of the total released IL-1 beta, as
      measured by SDS-PAGE with densitometry. This released proIL-1 beta was
      susceptible to ICE processing; however, this proIL-1 beta was not detectable by
      either a mature or proIL-1 beta-specific ELISA, suggesting that release induces a
      conformational change. The ELISA inability to detect proIL-1 beta was not due to
      inadequate sensitivity or subsequent degradation in the ELISA. Furthermore, while
      immunoaffinity-purified cytosolic proIL-1 beta could complex the type II IL-1R,
      released proIL-1 beta did not. Finally, the absence of a band shift in
      nondenaturing gel electrophoresis excluded proIL-1 beta binding to another
      protein. These findings imply that IL-1 beta is exported from monocytes as 3-, 17
      , 28-, and 31-kDa forms and that the released 31-kDa form differs from cytosolic
      proIL-1 beta.

PMID- 10202031
TI  - IL-3 and IL-4 activate cyclic nucleotide phosphodiesterases 3 (PDE3) and 4 (PDE4)
      by different mechanisms in FDCP2 myeloid cells.
AB  - In FDCP2 myeloid cells, IL-4 activated cyclic nucleotide phosphodiesterases PDE3
      and PDE4, whereas IL-3, granulocyte-macrophage CSF (GM-CSF), and phorbol ester
      (PMA) selectively activated PDE4. IL-4 (not IL-3 or GM-CSF) induced tyrosine
      phosphorylation of insulin-receptor substrate-2 (IRS-2) and its association with
      phosphatidylinositol 3-kinase (PI3-K). TNF-alpha, AG-490 (Janus kinase
      inhibitor), and wortmannin (PI3-K inhibitor) inhibited activation of PDE3 and
      PDE4 by IL-4. TNF-alpha also blocked IL-4-induced tyrosine phosphorylation of IRS
      2, but not of STAT6. AG-490 and wortmannin, not TNF-alpha, inhibited activation
      of PDE4 by IL-3. These results suggested that IL-4-induced activation of PDE3 and
      PDE4 was downstream of IRS-2/PI3-K, not STAT6, and that inhibition of tyrosine
      phosphorylation of IRS molecules might be one mechnism whereby TNF-alpha could
      selectively regulate activities of cytokines that utilized IRS proteins as signal
      transducers. RO31-7549 (protein kinase C (PKC) inhibitor) inhibited activation of
      PDE4 by PMA. IL-4, IL-3, and GM-CSF activated mitogen-activated protein (MAP)
      kinase and protein kinase B via PI3-K signals; PMA activated only MAP kinase via
      PKC signals. The MAP kinase kinase (MEK-1) inhibitor PD98059 inhibited IL-4-, IL
      3-, and PMA-induced activation of MAP kinase and PDE4, but not IL-4-induced
      activation of PDE3. In FDCP2 cells transfected with constitutively activated MEK,
      MAP kinase and PDE4, not PDE3, were activated. Thus, in FDCP2 cells, PDE4 can be
      activated by overlapping MAP kinase-dependent pathways involving PI3-K (IL-4, IL
      3, GM-CSF) or PKC (PMA), but selective activation of PDE3 by IL-4 is MAP kinase
      independent (but perhaps IRS-2/PI3-K dependent).

PMID- 10202032
TI  - Soluble murine IL-1 receptor type I induces release of constitutive IL-1 alpha.
AB  - IL-1 alpha and IL-1 beta are proinflammatory cytokines involved in the
      pathogenesis of many infectious and noninfectious inflammatory diseases. To
      reduce IL-1 toxicity, extracellular domains of the soluble (s) IL-1R are shed
      from cell membranes and prevent triggering of cell-bound receptors. We
      investigated to what extent murine sIL-1RI can neutralize the IL-1 produced by
      LPS-stimulated macrophages. When mouse peritoneal macrophages were incubated with
      LPS, addition of sIL-1RI significantly inhibited the bioactivity of IL-1.
      Stimulation of cells with sIL-1RI alone induced no bioactive IL-1. When
      immunoreactive cytokine concentrations were measured with specific
      radioimmunoassays, sIL-1RI alone appeared to induce a significant release of IL-1
      alpha in a concentration-dependent manner. This effect was independent of new
      protein synthesis. The production of IL-1 beta or TNF-alpha was not influenced by
      sIL-1RI. There was no interference of sIL-1RI with the IL-1 alpha
      radioimmunoassay. In mice, an i.v. injection of sIL-RI alone induced a rapid
      release of IL-1 alpha, but not of TNF-alpha or IL-1 beta. Treatment of mice with
      sIL-1RI improved the survival during a lethal infection with Candida albicans. In
      conclusion, sIL-1RI induces a rapid release of IL-1 alpha from cells, as well as
      into the systemic circulation. Although this IL-1 alpha may be inactivated in
      circulation by the same sIL-1RI, this phenomenon probably has immunostimulatory
      effects at local levels where the sIL-1RI-induced IL-1 alpha acts in a paracrine
      or autocrine manner.

PMID- 10202033
TI  - Human glioma-induced immunosuppression involves soluble factor(s) that alters
      monocyte cytokine profile and surface markers.
AB  - Patients with gliomas exhibit deficient in vitro and in vivo T cell immune
      activity, and human glioblastoma culture supernatants (GCS) inhibit in vitro T
      lymphocyte responses. Because APC are essential for initiating and regulating T
      cell responses, we investigated whether GCS would affect cytokines produced by
      monocytes and T cells from healthy donors of PBMC. Incubation of PBMC with GCS
      decreased production of IL-12, IFN-gamma, and TNF-alpha, and increased production
      of IL-6 and IL-10. The GCS-induced changes in IL-12 and IL-10 occurred in
      monocytes, and involved changes in IL-12 p40 and IL-10 mRNA expression.
      Incubation with GCS also resulted in reduced expression of MHC class II and of
      CD80/86 costimulatory molecules on monocytes. The immunosuppressive effects were
      not the result of IL-6 or TGF-beta1 that was detected in GCS. However, it was due
      to a factor(s) that is resistant to pH extremes, differentially susceptible to
      temperature, susceptible to trypsin, and has a minimum molecular mass of 40 kDa.
      Our findings show that glioblastoma-generated factors that are known to suppress
      T cell responses alter the cytokine profiles of monocytic APC that, in turn,
      inhibit T cell function. This model indicates that monocytes can serve as an
      intermediate between tumor-generated immune-suppressive factors and the T cell
      responses that are suppressed in gliomas.

PMID- 10202034
TI  - Extracellular-regulated kinase 1/2, Jun N-terminal kinase, and c-Jun are involved
      in NF-kappa B-dependent IL-6 expression in human monocytes.
AB  - In the present study we investigated the possible involvement of the mitogen
      activated protein kinase family members extracellular-regulated kinase 1/2
      (ERK1/2) and c-Jun N-terminal kinase (JNK) in mediating IL-6 gene expression in
      human monocytes, in particular their role in enhancing NF-kappa B activity.
      Freshly isolated monocytes treated with the protein phosphatase inhibitor okadaic
      acid secreted high levels of IL-6 protein, which coincided with enhanced binding
      activity of NF-kappa B as well as with phosphorylation and activation of the
      ERK1/2 and JNK proteins. The ERK pathway-specific inhibitor PD98059 inhibited IL
      6 secretion from monocytes. Transient overexpression of inactive mutants of
      either Raf-1 or JNK1 showed that both pathways were involved in kappa B-dependent
      IL-6 promoter activity. By using PD98059, we demonstrated that the
      Raf1/MEK1/ERK1/2 pathway did not affect the DNA binding of NF-kappa B but,
      rather, acted at the level of transcriptional activity of NF-kappa B.
      Interestingly, it was shown that NF-kappa B-mediated gene transcription, both in
      the context of the IL-6 promoter as well as on its own, was dependent on both
      serine kinase activity and interaction with c-Jun protein. We conclude that
      okadaic acid-induced IL-6 gene expression is at least partly mediated through the
      ERK1/2 and JNK pathway-dependent activation of NF-kappa B transcriptional
      capacity. Our results suggest that the JNK pathway may regulate NF-kappa B
      mediated gene transcription through its phosphorylation and activation of c-Jun.

PMID- 10202036
TI  - Inflammation alone evokes the response of a TCR-invariant mouse gamma delta T
      cell subset.
AB  - Whether gamma delta T lymphocytes respond to microbial Ags or to inducible host
      Ags remains a matter of controversy. Using several different disease models and
      mouse strains, we and others have seen that V gamma 6/V delta 1 gamma delta T
      cells preferentially increase among the gamma delta T cells infiltrating inflamed
      tissues. However, it was not clear whether bacteria are necessary to bring about
      this response. Therefore, we have reexamined this question using a disease model
      in which inflammation is induced by a purely autoimmune process involving no
      bacteria, bacterial products, or other foreign material: testicular cell-induced
      autoimmune orchitis. Using this model we found that gamma delta T cells were
      still plentiful among the infiltrating T lymphocytes, being 9- to 10-fold more
      prevalent than in spleen, and that V gamma 6/V delta 1+ cells again represented
      the predominant gamma delta T cell type. This finding shows that the response of
      the V gamma 6/V delta 1+ subset does not, in fact, depend upon the presence of
      bacteria or bacterial products. The stimulus triggering the response of the V
      gamma 6/V delta 1 gamma delta T cells appears to be neither foreign nor organ
      specific in origin, but instead consists of a self-derived host Ag or signal
      induced during the inflammatory process.

PMID- 10202035
TI  - CD26/dipeptidyl-peptidase IV down-regulates the eosinophil chemotactic potency,
      but not the anti-HIV activity of human eotaxin by affecting its interaction with
      CC chemokine receptor 3.
AB  - Chemokines attract and activate distinct sets of leukocytes. The CC chemokine
      eotaxin has been characterized as an important mediator in allergic reactions
      because it selectively attracts eosinophils, Th2 lymphocytes, and basophils.
      Human eotaxin has a penultimate proline, indicating that it might be a substrate
      for dipeptidyl-peptidase IV (CD26/DPP IV). In this study we demonstrate that
      eotaxin is efficiently cleaved by CD26/DPP IV and that the NH2-terminal
      truncation affects its biological activity. CD26/DPP IV-truncated eotaxin(3-74)
      showed reduced chemotactic activity for eosinophils and impaired binding and
      signaling properties through the CC chemokine receptor 3. Moreover, eotaxin(3-74)
      desensitized calcium signaling and inhibited chemotaxis toward intact eotaxin. In
      addition, HIV-2 infection of CC chemokine receptor 3-transfected cells was
      inhibited to a similar extent by eotaxin and eotaxin(3-74). Thus, CD26/DPP IV
      differently regulates the chemotactic and antiviral potencies of eotaxin by the
      removal of two NH2-terminal residues. This physiological processing may be an
      important down-regulatory mechanism, limiting eotaxin-mediated inflammatory
      responses.

PMID- 10202037
TI  - A circulating bovine gamma delta T cell subset, which is found in large numbers
      in the spleen, accumulates inefficiently in an artificial site of inflammation:
      correlation with lack of expression of E-selectin ligands and L-selectin.
AB  - Tissue-specific localization of TCR-defined subsets of gamma delta T cells has
      been widely reported; however, the mechanisms responsible for this phenomenon are
      poorly understood. We describe a bovine gamma delta T cell TCR-associated subset
      that preferentially localizes in the spleen. This subset was characterized by
      coexpression of CD8, and was found to lack surface expression of E-selectin
      ligands, GR Ag ligands, as well as low expression of L-selectin. The CD8-positive
      gamma delta T cell subset did not accumulate at sites of inflammation as
      efficiently as CD8-negative gamma delta T cells that, in contrast, express E
      selectin and GR ligands and high levels of L-selectin. This is the first
      demonstration of a gamma delta T cell subset, which exhibits a defined tissue
      tropism, having a unique adhesion molecule expression profile. These results
      demonstrate that in some cases tissue-specific accumulation of gamma delta T cell
      subsets can be predicted by expression, or lack of expression, of defined homing
      molecules.

PMID- 10202038
TI  - Characterization of CD44 induction by IL-1: a critical role for Egr-1.
AB  - The adhesion molecule CD44 is a multifunctional, ubiquitously expressed
      glycoprotein that participates in the process of leukocyte recruitment to sites
      of inflammation and to their migration through lymphatic tissues. In this study,
      we have investigated the effect of the proinflammatory cytokine IL-1alpha on CD44
      gene expression in the human immortalized endothelial cell line ECV304.
      Immunoblotting of cell extracts showed constitutive expression of a 85-kDa
      protein corresponding to the standard form of CD44, which was potently up
      regulated following IL-1alpha treatment. Furthermore, IL-1alpha induced
      expression of v3- and v6-containing isoforms of CD44, which migrated at 110 and
      140-180 kDa, respectively. The effect of IL-1alpha on CD44 standard, v3- and v6
      containing isoforms was dose and time dependent and was inhibited in the presence
      of IL-1 receptor antagonist. To elucidate the molecular mechanisms regulating
      CD44 expression in response to IL-1alpha, we investigated the effect of IL-1alpha
      on CD44 mRNA expression. Reverse-transcriptase PCR and Northern analysis
      demonstrated an increase in CD44 mRNA expression indicating a transcriptional
      mechanism of control by IL-1alpha. Furthermore, IL-1alpha increased expression of
      a reporter gene under the control of the CD44 promoter (up to -1.75 kb). The
      effect of IL-1alpha was critically dependent on the site spanning -151 to -701 of
      the promoter. This effect required the presence of an Egr-1 motif at position 
      301 within the CD44 promoter since mutation of this site abolished
      responsiveness. IL-1alpha also induced Egr-1 expression in these cells. These
      studies therefore identify Egr-1 as a critical transcription factor involved in
      CD44 induction by IL-1alpha.

PMID- 10202039
TI  - Gene expression and production of the monokine induced by IFN-gamma (MIG), IFN
      inducible T cell alpha chemoattractant (I-TAC), and IFN-gamma-inducible protein
      10 (IP-10) chemokines by human neutrophils.
AB  - Monokine induced by IFN-gamma (MIG), IFN-inducible T cell alpha chemoattractant
      (I-TAC), and IFN-gamma-inducible protein of 10 kDa (IP-10) are related members of
      the CXC chemokine subfamily that bind to a common receptor, CXCR3, and that are
      produced by different cell types in response to IFN-gamma. We have recently
      reported that human polymorphonuclear neutrophils (PMN) have the capacity to
      release IP-10. Herein, we show that PMN also have the ability to produce MIG and
      to express I-TAC mRNA in response to IFN-gamma in combination with either TNF
      alpha or LPS. While IFN-gamma, alone or in association with agonists such as
      fMLP, IL-8, granulocyte (G)-CSF and granulocyte-macrophage (GM)-CSF, failed to
      influence MIG, IP-10, and I-TAC gene expression, IFN-alpha, in combination with
      TNF-alpha, LPS, or IL-1beta, resulted in a considerable induction of IP-10
      release by neutrophils. Furthermore, IL-10 and IL-4 significantly suppressed the
      expression of MIG, IP-10, and I-TAC mRNA and the extracellular production of MIG
      and IP-10 in neutrophils stimulated with IFN-gamma plus either LPS or TNF-alpha.
      Finally, supernatants harvested from stimulated PMN induced migration and rapid
      integrin-dependent adhesion of CXCR3-expressing lymphocytes; these activities
      were significantly reduced by neutralizing anti-MIG and anti-IP-10 Abs,
      suggesting that they were mediated by MIG and IP-10 present in the supernatants.
      Since MIG, IP-10, and I-TAC are potent chemoattractants for NK cells and Th1
      lymphocytes, the ability of neutrophils to produce these chemokines might
      contribute not only to the progression and evolution of the inflammatory
      response, but also to the regulation of the immune response.

PMID- 10202040
TI  - Differential effects of leukotactin-1 and macrophage inflammatory protein-1 alpha
      on neutrophils mediated by CCR1.
AB  - The human CC chemokine leukotactin-1 (Lkn-1) is both a strong chemoattractant for
      neutrophils, monocytes, and lymphocytes and a potent agonist for CCR1 and CCR3.
      However, human neutrophils do not migrate when the cells are stimulated with
      other human CC chemokines, such as human macrophage inflammatory protein-1 alpha
      (hMIP-1 alpha) and eotaxin, which also use the CCR1 and CCR3 as their receptors.
      In this report, we demonstrate that while hMIP-1 alpha induced a negligible level
      of calcium flux and chemotaxis, Lkn-1 produced a high level of calcium flux and
      chemotaxis in human neutrophils. Lkn-1 cross-desensitized hMIP-1 alpha-induced
      calcium flux, but hMIP-1 alpha had little effect on the Lkn-1-induced response in
      human neutrophils. The same pattern was observed in peritoneal neutrophils from
      wild-type mice, whereas neutrophils from CCR1-/- mice failed to respond to either
      MIP-1 alpha or Lkn-1. Scatchard analysis revealed a single class of receptor for
      both hMIP-1 alpha and Lkn-1 on human neutrophils with dissociation constants (Kd)
      of 3.2 nM and 1.1 nM, respectively. We conclude that CCR1 is a receptor mediating
      responses to both MIP-1 alpha and Lkn-1 on neutrophils and produces different
      biological responses depending on the ligand bound.

PMID- 10202041
TI  - A fatal cytokine-induced systemic inflammatory response reveals a critical role
      for NK cells.
AB  - The mechanism of cytokine-induced shock remains poorly understood. The
      combination of IL-2 and IL-12 has synergistic antitumor activity in vivo, yet has
      been associated with significant toxicity. We examined the effects of IL-2 plus
      IL-12 in a murine model and found that the daily, simultaneous administration of
      IL-2 and IL-12 resulted in shock and 100% mortality within 4 to 12 days depending
      on the strain employed. Mice treated with IL-2 plus IL-12 exhibited NK cell
      apoptosis, pulmonary edema, degenerative lesions of the gastrointestinal tract,
      and elevated serum levels of proinflammatory cytokines and acute phase reactants.
      The actions of TNF-alpha, IFN-gamma, macrophage-inflammatory protein-1alpha, IL
      1, IL-1-converting enzyme, Fas, perforin, inducible nitric oxide synthase, and
      STAT1 did not contribute to the observed toxicity, nor did B or T cells. However,
      toxicity and death from treatment with IL-2 plus IL-12 could be completely
      abrogated by elimination of NK cells. These results suggest that the fatal
      systemic inflammatory response induced by this cytokine treatment is critically
      dependent upon NK cells, but does not appear to be mediated by the known effector
      molecules of this cellular compartment. These data may provide insight into the
      pathogenesis of cytokine-induced shock in humans.

PMID- 10202042
TI  - Endothelial targeting and enhanced antiinflammatory effects of complement
      inhibitors possessing sialyl Lewisx moieties.
AB  - The complement inhibitor soluble complement receptor type 1 (sCR1) and a
      truncated form of sCR1, sCR1[desLHR-A], have been generated with expression of
      the selectin-reactive oligosaccharide moiety, sialyl Lewisx (sLex), as N-linked
      oligosaccharide adducts. These modified proteins, sCR1sLex and sCR1[desLHR
      A]sLex, were assessed in the L-selectin- and P-selectin-dependent rat model of
      lung injury following systemic activation of complement by cobra venom factor and
      in the L-selectin-, P-selectin-, and E-selectin-dependent model of lung injury
      following intrapulmonary deposition of IgG immune complexes. In the cobra venom
      factor model, sCR1sLex and sCR1[desLHR-A]sLex caused substantially greater
      reductions in neutrophil accumulation and in albumin extravasation in lung when
      compared with the non-sLex-decorated forms. In this model, increased lung
      vascular binding of sCR1sLex and sCR1[desLHR-A]sLex occurred in a P-selectin
      dependent manner, in contrast to the absence of any increased binding of sCR1 or
      sCR1[desLHR-A]. In the IgG immune complex model, sCR1[desLHR-A]sLex possessed
      greater protective effects relative to sCR1[desLHR-A], based on albumin
      extravasation and neutrophil accumulation. Enhanced protective effects correlated
      with greater lung vascular binding of sCR1[desLHR-A]sLex as compared with the non
      sLex-decorated form. In TNF-alpha-activated HUVEC, substantial in vitro binding
      occurred with sCR1[desLHR-A]sLex (but not with sCR1[desLHR-A]). This endothelial
      cell binding was blocked by anti-E-selectin but not by anti-P-selectin. These
      data suggest that sLex-decorated complement inhibitors have enhanced
      antiinflammatory effects and appear to have enhanced ability to localize to the
      activated vascular endothelium.

PMID- 10202043
TI  - Role of TGF-beta 1 on the IgE-dependent anaphylaxis reaction.
AB  - TGF-beta1 is a member of a family of polypeptide factors that control
      proliferation, differentiation, chemotaxis, and other functions in many cell
      types. TGF-beta1 has been shown to inhibit many immunologic functions. However,
      here we report that TGF-beta1 has an important role in the elicitation of IgE
      dependent allergic reactions. The synthetic antisense TGF-beta1 oligonucleotides
      dose-dependently inhibit passive cutaneous anaphylaxis (PCA) reaction and
      histamine release from the mast cells activated by anti-DNP IgE in rats. The
      level of cAMP in mast cells, when antisense TGF-beta1 oligonucleotides was added,
      significantly increased approximately 7-fold compared with that of basal cells.
      The antisense TGF-beta1 oligonucleotides also had a significant inhibitory effect
      on anti-DNP IgE-induced TNF-alpha release from mast cells. In situ hybridization
      analysis showed that the PCA reaction sites treated with antisense TGF-beta1
      oligonucleotides exhibited no detectable levels of TGF-beta1 and L-histidine
      decarboxylase mRNA after anti-DNP IgE stimulation, whereas the PCA reaction sites
      treated with sense TGF-beta1 oligonucleotides possessed significant amounts of
      their mRNA. Additionally, neutralizing Ab to TGF-beta1 blocked the PCA reaction
      significantly, but its Ab did not inhibit peritoneal mast cell-released histamine
      upon treatment with anti-DNP IgE. Our results suggest that TGF-beta1 is critical
      to the development of IgE-dependent anaphylaxis reactions.

PMID- 10202044
TI  - Development of an animal model of autoimmune thyroid eye disease.
AB  - In previous studies we have transferred thyroiditis to naive BALB/c and NOD mice
      with human thyrotropin (TSH) receptor (TSHR)-primed splenocytes. Because the TSHR
      has been implicated in the pathogenesis of thyroid eye disease (TED) we have
      examined the orbits of recipients of TSHR-primed T cells, generated using a TSHR
      fusion protein or by genetic immunization. In the NOD mice, 25 of 26 animals
      treated with TSHR-primed T cells developed thyroiditis with considerable
      follicular destruction, numerous activated and CD8+ T cells, and immunoreactivity
      for IFN-gamma. Thyroxine levels were reduced. Thyroiditis was not induced in
      controls. None of the NOD animals developed any orbital pathology. Thirty-five
      BALB/c mice received TSHR-primed spleen cells. Thyroiditis was induced in 60-100%
      and comprised activated T cells, B cells, and immunoreactivity for IL-4 and IL
      10. Autoantibodies to the receptor were induced, including TSH binding inhibiting
      Igs. A total of 17 of 25 BALB/c orbits displayed changes consisting of
      accumulation of adipose tissue, edema caused by periodic acid Schiff-positive
      material, dissociation of the muscle fibers, the presence of TSHR
      immunoreactivity, and infiltration by lymphocytes and mast cells. No orbital
      changes or thyroiditis were observed in control BALB/c mice. We have induced
      orbital pathology having many parallels with human TED, only in BALB/c mice,
      suggesting that a Th2 autoimmune response to the TSHR may be a prerequisite for
      the development of TED.

PMID- 10202045
TI  - Administration of mAb against alpha E beta 7 prevents and ameliorates
      immunization-induced colitis in IL-2-/- mice.
AB  - We previously demonstrated that 2,4,6-trinitrophenol (TNP)-OVA immunization leads
      to a transmural colitis in the IL-2-/- mouse that is caused by IL-12-driven CD4+
      Th1 T cells and resembles human Crohn's disease. The integrin alpha E beta 7 is
      highly expressed on colonic intraepithelial lymphocytes and has been suggested to
      function as a homing or retention molecule for intraepithelial lymphocytes. To
      evaluate the role of alpha E beta 7 in colitis, we administered a mAb against
      alpha E beta 7 to IL-2-/- mice that were immunized at the same time with TNP-OVA
      in CFA. To our surprise, this treatment resulted in a significantly reduced
      colitis severity score, 0-2 vs 3-4, that was associated with a significant
      reduction in CD4+ lamina propria lymphocyte subpopulation (p < 0.01). In
      contrast, the total number of splenic CD4+ T cells of treated animals was
      significantly elevated compared with that of untreated animals (3.2 +/- 0.6 x 107
      vs 1.2 +/- 0.2 x 107; p < 0.05). Similarly, functional studies revealed that IFN
      gamma production by lamina propria lymphocytes isolated from IL-2-/- TNP-OVA
      immunized mice treated with anti-alpha E beta 7 was significantly lower than in
      untreated IL-2-/- TNP-OVA-immunized mice. In contrast, IFN-gamma production by
      splenic cells isolated from treated IL-2-/- TNP-OVA-immunized mice was
      significantly higher than in untreated mice. Finally, TNP-OVA-immunized IL-2-/-
      mice that were treated after the colitis had been established also showed a
      significant decrease in mucosal inflammation after alpha E beta 7 mAb
      administration. Thus, the above findings demonstrate that the onset and
      maintenance of inflammatory bowel disease depends on the colonic localization of
      lamina propria CD4+ lymphocytes expressing alpha E beta 7.

PMID- 10202047
TI  - Identification and characterization of epitopes recognized by T lymphocytes and
      autoantibodies from patients with herpes gestationis.
AB  - Autoantibodies associated with herpes gestationis (HG), a pregnancy-associated
      autoimmune skin disease, target the hemidesmosomal protein BP180. It was shown
      that the major noncollagenous stretch of the BP180 ectodomain (NC16A) harbors
      epitopes recognized by HG sera. Furthermore, Abs reactive with the homologous
      domain of murine BP180 are known to trigger a cutaneous blistering disease in
      mice by passive transfer experiments. The present study was aimed at
      characterizing the T cell responses and specificities of autoantibodies from two
      HG patients. Using immunoblotting and T cell proliferation assays, we have
      identified a 14-amino-acid stretch of the BP180 ectodomain (MCW-1; aa 507-520)
      that is recognized by both T cells and autoantibodies produced by the HG
      patients. The neonate born to one of these HG patients showed no signs of skin
      disease and had no detectable T cell response to the BP180 Ag, but did have a low
      titer of circulating anti-BP180 autoantibodies, presumably of maternal origin.
      BP180-specific T cell lines and clones developed from an HG patient specifically
      reacted with the MCW-1 epitope. The proliferative responses of these clones were
      restricted to HLA-DR, but not -DQ or -DP. These Ag-specific T cells expressed
      alpha/beta TCRs and a CD4 memory T cell phenotype and secreted IFN-gamma and IL
      2, but not IL-4 or IL-6, suggesting that they are Th1-type lymphocytes. Further
      characterization of these Ag-specific T cells and autoantibodies will aid in
      elucidating the autoimmune mechanism(s) leading to the development of HG.

PMID- 10202046
TI  - CTLA4 signals are required to optimally induce allograft tolerance with combined
      donor-specific transfusion and anti-CD154 monoclonal antibody treatment.
AB  - Sensitization to donor Ags is an enormous problem in clinical transplantation. In
      an islet allograft model, presensitization of recipients through donor-specific
      transfusion (DST) 4 wk before transplantation results in accelerated rejection.
      We demonstrate that combined DST with anti-CD154 (CD40L) therapy not only
      prevents the deleterious presensitization produced by pretransplant DST in the
      islet allograft model, it also induces broad alloantigen-specific tolerance and
      permits subsequent engraftment of donor islet or cardiac grafts without further
      treatment. In addition, our data strongly indicate that CTLA4-negative T cell
      signals are required to achieve prolonged engraftment of skin allograft or
      tolerance to islet allograft in recipients treated with a combination of
      pretransplant DST and anti-CD154 mAb. We provide direct evidence that a CD28
      independent CTLA4 signal delivers a strong negative signal to CD4+ T cells that
      can block alloimmune MLR responses. In this study immune deviation into a Th2 (IL
      4) response was associated with, but did not insure, graft tolerance, as the
      inopportune timing of B7 blockade with CTLA4/Ig therapy prevented uniform
      tolerance but did not prevent Th2-type immune deviation. While CTLA4-negative
      signals are necessary for tolerance induction, Th1 to Th2 immune deviation cannot
      be sufficient for tolerance induction. Combined pretransplant DST with anti-CD154
      mAb treatment may be attractive for clinical deployment, and strategies aimed to
      selectively block CD28 without interrupting CTLA4/B7 interaction might prove
      highly effective in the induction of tolerance.

PMID- 10202048
TI  - Glutamate augments retrovirus-induced immunodeficiency through chronic
      stimulation of the hypothalamic-pituitary- adrenal axis.
AB  - The mechanisms for activating the hypothalamic-pituitary-adrenal (HPA) axis and
      the roles glucocorticoids play in the pathogenesis of chronic infectious disease
      are largely undefined. Using the LP-BM5 model of retrovirus-induced
      immunodeficiency, we found alterations in HPA axis function, manifested as an
      increase in circulating levels of adrenocorticotropic hormone and corticosterone,
      beginning after only 3 mo of infection. These changes occurred contemporaneously
      with a shift in the profile of circulating cytokines from a Th1-dominant (IFN
      gamma) to Th2-dominant (IL-4, IL-10) phenotype. No significant changes in either
      circulating IL-1beta, IL-6, or TNF-alpha levels were observed in infected mice.
      Administering the N-methyl-D-aspartate receptor antagonist MK-801 to infected
      mice normalized plasma adrenocorticotropic hormone and corticosterone levels,
      indicating that glutamate was a major activator of the HPA axis. Moreover, MK-801
      treatment of late-stage mice also reversed the type 1 to type 2 cytokine shift to
      a degree comparable or superior to treatment with the glucocorticoid receptor
      antagonist RU-486. These findings indicate that HPA axis activation during LP-BM5
      retrovirus infection is mediated by the chronic hyperactivation of glutamatergic
      pathways in the hypothalamus. Through this mechanism, the degree of peripheral
      immunodeficiency observed in the late-stage disease is profoundly augmented.

PMID- 10202049
TI  - 4-1BBL cooperates with B7-1 and B7-2 in converting a B cell lymphoma cell line
      into a long-lasting antitumor vaccine.
AB  - A20 is a B cell lymphoma that constitutively expresses the costimulatory molecule
      B7-2 yet grows readily as a tumor in syngeneic BALB/c mice. We have compared the
      tumorigenicity of A20 variants expressing either B7-1 (A20/B7-1) or B7-2 (A20/B7
      2) with an A20 variant expressing B7-1 and B7-2 with 4-1BBL (A20/4-1BBL), a
      costimulatory member of the TNF family. Mice injected with tumors expressing the
      vector backbone (A20/CMV) or B7-1 developed tumors within 25 days of s.c.
      injection. In contrast, mice injected with A20/4-1BBL were tumor free for the 150
      day follow-up period, while 25% of mice injected with A20/B7-2 developed tumors.
      Tumorigenicity experiments using nude mice indicated the requirement for T cells
      for variant rejection. Almost all mice that resisted the initial tumor challenge
      were resistant to further challenge with the parental tumor. Splenocytes from
      these mice showed high CTL lytic activity against the parental tumor, A20, as
      well as the syngeneic BALB/c lymphoma K46J, but showed background levels of lytic
      activity against the congenic SCID thymoma line ST-D2 or the allogeneic EL4
      thymoma. In vitro blocking experiments with anti-B7-1 plus anti-B7-2 and/or
      soluble 4-1BB receptor showed B7-1, B7-2, and 4-1BBL all contributed to the CTL
      activity. Thus, the data show that neither B7-1 or B7-2 alone can confer full
      immunogenicity to the A20 lymphoma but that the addition of 4-1BBL results in a
      tumor that is highly immunogenic and can confer long-lasting protection against
      challenge with parental tumor in vivo.

PMID- 10202050
TI  - Induction of mucosal immunity by inactivated poliovirus vaccine is dependent on
      previous mucosal contact with live virus.
AB  - The inactivated poliovirus vaccine (IPV) is used for protection against
      poliomyelitis in The Netherlands. It is not clear, however, whether IPV
      vaccination can lead to priming of the mucosal immune system and the induction of
      IgA. It has been demonstrated that IPV vaccination is able to induce strong
      memory IgA responses in the serum of persons who have been naturally exposed to
      wild-type poliovirus. This has led to the hypothesis that IPV vaccination is able
      to induce poliovirus-specific IgA at mucosal sites in persons who have been
      previously primed with live poliovirus at mucosal sites. To test this hypothesis,
      the kinetics of the IgA response in serum and saliva after IPV vaccination were
      examined in persons previously vaccinated with oral poliovirus vaccine (OPV) or
      IPV. ELISA and enzyme-linked immunospot assays were used for the detection of
      poliovirus-specific IgA responses. In addition, B cell populations were separated
      on the basis of the expression of mucosal (alpha4beta7 integrin) and peripheral
      homing receptors (L-selectin). Parenteral IPV vaccination was able to boost
      systemic and mucosal IgA responses in previously OPV-vaccinated persons only.
      None of the previously vaccinated IPV recipients responded with the production of
      IgA in saliva. In agreement with this finding, a large percentage of the
      poliovirus-specific IgA-producing lymphocytes detected in previous OPV recipients
      expressed the alpha4beta7 integrin. It is concluded that IPV vaccination alone is
      insufficient to induce a mucosal IgA response against poliovirus. In mucosally
      (OPV-) primed individuals, however, booster vaccination with IPV leads to a
      strong mucosal IgA response.

PMID- 10202051
TI  - Mutations that cause the Wiskott-Aldrich syndrome impair the interaction of
      Wiskott-Aldrich syndrome protein (WASP) with WASP interacting protein.
AB  - Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder characterized by
      thrombocytopenia, eczema, immune deficiency, and a proclivity toward lymphoid
      malignancy. Lymphocytes of affected individuals show defects of activation,
      motility, and cytoskeletal structure. The disease gene encodes a 502-amino acid
      protein named the WAS protein (WASP). Studies have identified a number of
      important interactions that place WASP in a role of integrating signaling
      pathways with cytoskeletal function. We performed a two-hybrid screen to identify
      proteins interacting with WASP and cloned a proline-rich protein as a specific
      WASP interactor. Our clone of this protein, termed WASP interacting protein (WIP)
      by others, shows a difference in seven amino acid residues, compared with the
      previously published sequence revealing an additional profilin binding motif.
      Deletion mutant analysis reveals that WASP residues 101-151 are necessary for
      WASP-WIP interaction. Point mutant analyses in the two-hybrid system and in vitro
      show impairment of WASP-WIP interaction with three WASP missense mutants known to
      cause WAS. We conclude that impaired WASP-WIP interaction may contribute to WAS.

PMID- 10202052
TI  - Variceal ligation compared with endoscopic sclerotherapy for variceal hemorrhage:
      prospective randomized trial.
AB  - BACKGROUND: To evaluate the safety and efficiency of variceal ligation compared
      with endoscopic sclerotherapy, 88 patients with cirrhosis with recent variceal
      bleeding were randomized to undergo either treatment. METHODS: Sclerotherapy was
      performed using ethanolamine and polidocanol injection at 1, 2, and 3 weeks and
      every 3 weeks thereafter. The Stiegmann-Goff device was used for variceal
      ligation at the same intervals. RESULTS: The rate of variceal eradication was the
      same for both groups, but eradication was accomplished sooner in patients
      undergoing variceal ligation (5.3+/-1.6 vs. 6.6+/-2.4 endoscopic sessions, p <
      0.05) and with fewer complications (19 vs. 6, p < 0.005). The rate of recurrent
      bleeding was lower in patients treated by ligation (31% vs. 50%, p < 0.05). After
      eradication, variceal recurrence was more frequent in patients treated by
      variceal ligation at 1 and 3 years (47% and 92% vs. 23% and 55%, p < 0.01).
      Portal hypertensive gastropathy was significantly worse in the patients who had
      variceal ligation (17 patients vs. 6, p < 0.01). Survival and treatment failure
      were similar in both groups. CONCLUSIONS: Variceal ligation was superior to
      sclerotherapy in terms of the rate of recurrent bleeding and the occurrence of
      complications but worse with respect to recurrence of varices and the evolution
      of portal hypertensive gastropathy. Long-term follow-up studies are required to
      find out whether there are deleterious effects of variceal ligation.

PMID- 10202053
TI  - High-resolution endoluminal sonography assessment of the hematocystic spots of
      esophageal varices.
AB  - BACKGROUND: Many variables are associated with an increased potential for
      esophageal variceal rupture, especially the presence of hematocystic spots and
      other red signs on upper endoscopy. The etiology of hematocystic spots is
      unknown. High-resolution endoluminal sonography has been shown to be an accurate
      and sensitive imaging modality for detection, as well as the qualitative and
      quantitative assessment of esophageal varices. Because the high-resolution
      endoluminal sonography transducer permits detailed resolution of submucosal
      structures thereby allowing more precise examination of the actual wall of the
      varix, we sought to image variceal hematocystic spots in an effort to better
      define their anatomy. METHODS: Simultaneous upper endoscopy and high-resolution
      endoluminal sonography were performed in 68 patients with cirrhosis. Endoscopy
      was performed as part of screening for varices during evaluation for liver
      transplantation or in patients with previous presumed variceal bleeding. On
      endoscopy and high-resolution endoluminal sonography, two independent reviewers
      identified the same 10 patients having esophageal varices with hematocystic
      spots. The patients who had bled from their varices had not received prior
      endoscopic treatment. RESULTS: Hematocystic spots as seen with high-resolution
      endoluminal sonography imaging appeared as saccular aneurysm like projections on
      the variceal surface in 6 of 10 patients. Four of six patients would later have
      recurrent bleeding; two of these patients were again noted to have hematocystic
      spots on endoscopy with a similar corresponding high-resolution endoluminal
      sonography appearance. Patients without hematocystic spots did not have similar
      high-resolution endoluminal sonography imaging. CONCLUSION: Aneurysm-like
      projections in the wall of varices may represent focal weaknesses of the variceal
      wall and thus play a role in the pathophysiology of esophageal variceal rupture.
      The present findings may help to explain why there is an increased risk of
      variceal hemorrhage associated with the presence of hematocystic spots on
      esophageal varices.

PMID- 10202055
TI  - Gastric variceal ligation: a new technique.
AB  - BACKGROUND: Gastric variceal bleeding is a serious complication of portal
      hypertension. The role of endoscopy in its management is still controversial.
      However, band ligation of gastric varices has not been evaluated. This study
      prospectively describes gastric variceal ligation as a new endoscopic technique
      for the management of different types of gastric varices. METHODS: Gastric
      variceal ligation was performed in 27 patients with gastric varices: 3 patients
      had type 1 gastroesophageal varices, 14 had type 2, 8 had isolated gastric
      varices, and 2 had both type 1 and type 2 gastroesophageal varices. The etiology
      of portal hypertension was schistosomiasis in 9, post hepatic cirrhosis in 3, and
      mixed cirrhosis in 15 patients. The Child-Pugh classification was grade A in 6, B
      in 17, and C in 4 cases. Active variceal bleeding was present in 18 patients,
      whereas nonbleeding varices were encountered in 9 patients. RESULTS: Emergency
      gastric variceal ligation arrested bleeding in 16 of 18 patients (88.8%).
      Recurrent bleeding was noted in 5 of 27 (18.5%). Six patients died (22.2%), 3 due
      to recurrent bleeding and 2 to liver failure. Variceal obliteration was achieved
      in all patients who underwent repeated elective sessions. The number of sessions
      needed for obliteration of varices was significantly less in patients with
      isolated gastric varices when compared with those with type 1 gastroesophageal
      varices ( p < 0.04). No serious complications occurred. CONCLUSION: Gastric
      variceal ligation is a safe and effective treatment for the different types of
      gastric varices but especially isolated gastric varices.

PMID- 10202054
TI  - Prevalence of paraesophageal varices and gastric varices in patients achieving
      variceal obliteration by banding ligation and by injection sclerotherapy.
AB  - BACKGROUND: The impact of banding ligation and injection sclerotherapy on
      paraesophageal varices and gastric varices has received scarce attention. We
      conducted a study using endoscopic ultrasound (EUS) to visualize paraesophageal
      varices and gastric varices in patients who underwent sclerotherapy and banding
      ligation. METHODS: Patients with esophageal variceal bleeding whose varices were
      obliterated by ligation (44 patients) and by sclerotherapy (35 patients) were
      enrolled. EUS was used to compare the prevalences of paraesophageal varices and
      gastric varices between the treatment groups. The correlation between
      paraesophageal varices and esophageal variceal recurrence and recurrent bleeding
      was assessed. RESULTS: The prevalence of paraesophageal varices was 86% in the
      ligation group compared with 51% in the sclerotherapy group (p = 0.002). The
      prevalence of gastric varices was slightly higher in the ligation group than in
      the sclerotherapy group (43% vs. 26%, p = 0.18). Esophageal varices recurred in
      70% of the ligation group and 43% of the sclerotherapy group (p = 0.04). Patients
      in both groups with more severe paraesophageal varices had a significantly higher
      rate of variceal recurrence (p = 0.002 in ligation group and p = 0.001 in
      sclerotherapy group). Bleeding recurred in 6 patients in the ligation group and 4
      patients in the sclerotherapy group. All patients with recurrent bleeding had
      paraesophageal varices. The rate of recurrent bleeding was significantly higher
      in patients with paraesophageal varices (p < 0.0001). CONCLUSIONS: EUS was
      helpful in the imaging of paraesophageal and gastric varices after sclerotherapy
      or banding ligation. Paraesophageal varices were more frequently noted in
      patients undergoing ligation. The presence of paraesophageal varices may predict
      the recurrence of esophageal varices and recurrent bleeding.

PMID- 10202056
TI  - Laser and multipolar electrocoagulation ablation of early Barrett's
      adenocarcinoma: long-term follow-up.
AB  - BACKGROUND: Endoscopic ablation of Barrett's esophagus, including associated
      dysplasia and adenocarcinoma, can be achieved by various techniques, but few long
      term results are available. The aim of our study was ablation of intramucosal
      adenocarcinoma with a combination of Nd:YAG laser plus multipolar
      electrocoagulation. METHODS: Patients with documented Barrett's esophagus and
      adenocarcinoma who either had refused surgery or were poor candidates for surgery
      because of high risk were offered endoscopic therapy. Patients underwent therapy
      with Nd:YAG laser and multipolar electrocoagulation. They were treated with
      omeprazole (20 mg twice daily) as maintenance therapy. RESULTS: Six patients were
      enrolled in the study over a 7-year period. All were men with a mean age of 78.2
      years. The mean length of Barrett's esophagus was 6.0 cm (range, 3 to 10 cm).
      Seventeen Nd:YAG laser (mean, 2.8/patient) and 20 multipolar electrocoagulation
      (mean, 3.3/patient) sessions were used during the study period. All patients had
      a complete initial response to therapy. One patient on chronic immunosuppressive
      medications had recurrence of the tumor after an initial complete response (36
      month follow-up). Two patients have no evidence of Barrett's esophagus, and 3
      patients have residual intestinal metaplasia on biopsy of an irregular appearing
      "neo" Z-line. Mean follow-up in this group is 3.4 years (range, 9 to 86 months).
      CONCLUSIONS: Laser photocoagulation and multipolar electrocoagulation can be
      successfully and safely used to ablate intramucosal adenocarcinoma in the setting
      of Barrett's esophagus. Patients remain functional with normal swallowing.

PMID- 10202058
TI  - Mucosal exposure to light during routine endoscopy.
AB  - BACKGROUND: The spectral irradiance delivered by a variety of gastrointestinal
      endoscopes was measured as a function of wavelength and used to estimate the
      amount of light delivered to the mucosal surface during routine endoscopic
      procedures. METHODS: Spectral irradiances from seven different endoscopes were
      measured using a commercial spectroradiometer calibrated against a National
      Institute of Standards and Technology traceable source. RESULTS: The largest
      maximum irradiance was 8.0 W/cm2 obtained from an endoscope used in
      transillumination mode. In the typical viewing mode, the largest maximum
      irradiance measured was 1.6 W/cm2. The majority of the light energy delivered by
      these gastrointestinal endoscopes was in the visible wavelength region (400 to
      700 nm). DISCUSSION: The measurements revealed surprisingly high light exposures
      in the visible wavelength range. In fact, the estimated tissue exposures can
      exceed by 40-fold the standards established for skin exposure to light set forth
      by the American National Standards Institute. Because gastrointestinal endoscopy
      is widely viewed to be safe, it is probable that the gastrointestinal tract has
      significant tolerance to light exposure.

PMID- 10202057
TI  - In vivo identification of colonic dysplasia using fluorescence endoscopic
      imaging.
AB  - BACKGROUND: Previous in vitro studies showed that autofluorescence images of
      colonic mucosa collected endoscopically can be used to detect dysplasia with high
      sensitivity. This method is extended to the collection of fluorescence images of
      adenomatous polyps in vivo. METHODS: Fluorescence images were collected during
      colonoscopy in 30 patients. A total of 12 adenomatous and 6 hyperplastic polyps
      were identified. A fiberoptic excitation probe, located in the instrument channel
      of the colonoscope, delivered 300 mW of near-ultraviolet light at lambdaex = 351
      and 364 nm. Mucosal fluorescence in the spectral bandwidth between 400 and 700 nm
      was imaged, processed, and displayed with various likelihoods of associated
      dysplasia. RESULTS: Adenomatous polyps exhibited decreased fluorescence intensity
      compared with adjacent mucosa with normal appearance. With the fluorescence
      threshold set to 80% of the average intensity of normal mucosa, a sensitivity of
      83% for dysplasia identification was achieved. All hyperplastic polyps were
      correctly identified as being non-dysplastic. Optimal identification of
      dysplastic regions was obtained with the colonoscope oriented at a near-normal
      angle of incidence to the polyps. At higher angles of incidence, artifacts caused
      by illumination shadows were introduced. CONCLUSIONS: The dysplasia associated
      with adenomatous polyps can be identified in vivo by fluorescence imaging with
      high sensitivity, thus demonstrating the potential to guide endoscopic
      procurement of biopsy specimens.

PMID- 10202059
TI  - A comparison study on physical properties of self-expandable esophageal metal
      stents.
AB  - BACKGROUND: Currently available esophageal expandable stents differ in design,
      material, and method of deployment. We compared the expansile force and the
      susceptibility to buckling force in five commercially available stents. METHODS:
      The Esophacoil, Wallstent, Ultraflex, Gianturco-Z and Song stents were tested.
      The middle sections of fully expanded stents were subjected to compression force
      using a universal tensile testing machine. The distortion of the stent was
      measured electronically and the expansile force was calculated. Bending moments
      were applied to the ends of the stents until buckling occurred in the inner
      parts. The buckling radius was measured as the radius of the inner curvature of
      the stent when this occurred. RESULTS: The stents tested were significantly
      different in their expansile forces and buckling radii. Song stent and Gianturco
      Z stent were similar due to their similar designs. Esophacoil was the strongest
      with regard to withstanding compressive force and angulation force, followed by
      Wallstent. Ultraflex stent was the weakest in expansile force but withstood
      angulation force better than the Song and Gianturco stents. CONCLUSION:
      Esophageal stents differ greatly in their elasticity and resistance to
      angulation. Knowledge of their mechanical properties will be another helpful
      factor to consider in selecting the appropriate stent in addition to the geometry
      and consistency of the tumor.

PMID- 10202060
TI  - Comparative costs of metal versus plastic biliary stent strategies for malignant
      obstructive jaundice by decision analysis.
AB  - BACKGROUND: For palliation of patients with malignant obstructive jaundice,
      expansile metal stents provide longer patency than plastic stents but are more
      expensive. The optimal cost-effective strategy has not been established. Our aim
      was to compare the relative costs of 3 strategies: (1) plastic stent, with
      exchange on occlusion; (2) metal stent initially, with coaxial plastic stent
      insertion in the event of occlusion; or (3) plastic stent initially, with metal
      stent exchange in the event of occlusion. METHODS: A decision analysis model was
      created using DATA 2.6 software to assess the relative costs of the three
      strategies. Values for variables including the probabilities of reintervention
      and patient survival were obtained from published data. Costs were based on
      Medicare reimbursements of hospital charges, and the model was evaluated from the
      perspective of a third-party payer. One-way and two-way sensitivity analysis of
      the variables was performed over a wide range. RESULTS: The outcome is highly
      sensitive to the ratio of metal stent cost relative to endoscopic retrograde
      cholangiopancreatography cost (cost ratio M:ERCP) and to the length of survival
      of the patient. The most economical strategies were (2), (3) and (1) for M:ERCP
      cost ratios of <0.5, 0.5 to 0.7, and >0.7, respectively. CONCLUSIONS: The choice
      of stent should be guided by the relative local costs of ERCP and metal stents
      and by the prognosis of the patient. At current metal stent costs and Medicare
      reimbursement rates, initial placement of a plastic stent, followed by metal
      stent placement at first occlusion in longer survivors, is an economical option.
      If metal stent cost is less than half of ERCP cost, then initial insertion of a
      metal stent would be most economical. Use of plastic stents is preferable for
      patients surviving less than 4 months, whereas metal stents are more economical
      for patients with longer survival.

PMID- 10202061
TI  - Pancreatitis induced by endoscopic balloon sphincter dilation and changes in
      serum amylase levels after the procedure.
AB  - BACKGROUND: The short-term safety of endoscopic balloon sphincter dilation
      remains to be defined. We prospectively investigated the rate of pancreatitis and
      changes in pancreatic enzyme values induced by endoscopic balloon sphincter
      dilation. METHODS: One hundred nine patients with bile duct stones were treated
      using endoscopic balloon sphincter dilation between July 1995 and September 1997.
      Serum amylase values were determined before and after the procedure in 100
      patients treated 106 times, and these values were compared with the incidence of
      pancreatitis. Patients were classified into 3 categories according to serum
      amylase levels before therapy (group A, within the normal range; group B, above
      the normal upper limit up to 500 mU/mL; group C, above 500 mU/mL). The severity
      of pancreatitis was categorized into 4 grades (minimal, postprocedural abdominal
      pain lasting no longer than the next morning; mild, elevation of amylase values
      to at least three times normal accompanied by postprocedural abdominal pain
      necessitating treatment for 3 nights; moderate, required 4 to 10 nights of
      treatment; severe, required intensive care). RESULTS: Postprocedural serum
      amylase levels in groups A and B were significantly elevated compared with
      baseline levels. In contrast, these levels in group C were decreased. Overall,
      postprocedural amylase levels were elevated in 95 studies. Minimal or mild
      pancreatitis developed in 21 (15 minimal and 6 mild) patients in groups A and B
      only. CONCLUSIONS: Although pancreatic serum enzymes were elevated in almost all
      patients after endoscopic balloon sphincter dilation, procedure-related
      pancreatitis developed in a small percentage. There does not seem to be any
      contraindication to the use of endoscopic balloon sphincter dilation in patients
      with high amylase levels and an indication for the procedure, although such
      patients sometimes have stone-related pancreatitis or may be predisposed to
      developing pancreatitis.

PMID- 10202062
TI  - In vitro and in vivo evaluation of a reusable double-channel sphincterotome.
AB  - BACKGROUND: To date, one reusable, double-channel sphincterotome has been
      approved by the Food and Drug Administration in the United States. Whether this
      device can be reprocessed easily and whether it is more durable than currently
      manufactured disposable sphincterotomes are uncertain. METHODS: Thirty double
      channel, 20 mm, braided-wire sphincterotomes approved for multiple uses were
      studied in vitro/in vivo with regard to durability and sterilization. A cost
      analysis of reusable, disposable, and reprocessed disposable sphincterotomes was
      also carried out. RESULTS: Three of 10 sphincterotomes evaluated in vitro broke
      after 3, 4, and 8 uses. Electrical integrity was preserved after 10 uses in the
      remaining sphincterotomes. Nine sphincterotomes remained functional for at least
      3 uses, five for 6 uses, and one for 10 uses. Culture results after inoculation
      demonstrated contamination with surviving organisms after manual cleaning and no
      growth after ethylene oxide sterilization. Sixty-one procedures were performed in
      vivo using 20 sphincterotomes (mean number of uses 3.1). No evidence of
      procedurally related infection occurred with reuse. Cost per use of this reusable
      sphincterotome was calculated to be $62.98; it became cost effective after 2.2
      and 7.9 uses when compared with disposable and reprocessed, disposable
      sphincterotomes, respectively. CONCLUSIONS: This reusable sphincterotome proved
      to be safe, easily sterilized, and electrically intact after repeated use. In
      vivo, however, a progressive loss of function limited the mean number of uses to
      3.1. In settings that preclude reuse of reprocessed disposable accessories, this
      reusable sphincterotome may provide a means to decrease costs associated with
      endoscopic retrograde cholangiopancreatography.

PMID- 10202063
TI  - Does cholecystectomy after endoscopic sphincterotomy prevent the recurrence of
      biliary complications?
AB  - BACKGROUND: The intact gallbladder after endoscopic sphincterotomy is thought to
      be a potential risk factor for recurrent biliary complications. The aim of this
      non-randomized prospective study was to investigate whether cholecystectomy soon
      after endoscopic sphincterotomy could prevent the recurrence of biliary
      complications. METHODS: From January 1991 to October 1995, 140 patients with
      intact gallbladder underwent endoscopic sphincterotomy for clearance of stones in
      the bile duct. Of the 140 patients, 46 underwent elective cholecystectomy soon
      after sphincterotomy (group A) and 94 did not (group B). All 140 patients had
      quantitative cholescintigraphy after normalization of liver function and were
      followed on a regular basis with liver biochemistry, sonography, and/or computed
      tomography. Endoscopic retrograde cholangiography was also performed if a
      recurrent biliary problem was suspected. RESULTS: After a median 43 months (range
      23 to 80) of follow-up, 5 patients in group A developed bile duct stones whereas
      12 patients in group B had recurrent stones; 4 patients in group A versus 6
      patients in group B had recurrent biliary symptoms. One patient in group A and 5
      patients in group B with recurrent biliary stones were without symptoms. In group
      B, the age, gender, diameter of the bile duct, preexisting cholelithiasis,
      abnormal filling of the gallbladder on quantitative cholescintigraphy, and
      presence of juxtapapillary diverticulum were not found to be the significant
      factors affecting the recurrence of biliary symptoms or stones. Endoscopic
      removal of recurrent biliary stones was successful in all patients. Three
      patients in group B underwent cholecystectomy after abatement of symptoms.
      CONCLUSION: Elective cholecystectomy after endoscopic sphincterotomy does not
      reduce the incidence of recurrent biliary complications.

PMID- 10202064
TI  - Preoperative assessment of congenital bile duct dilatation using intraductal US.
AB  - BACKGROUND: Although congenital bile duct dilatation is frequently associated
      with biliary tract cancer, conventional cholangiography often does not
      demonstrate small ductal tumors. This is the first prospective study of the value
      of intraductal ultrasonography (US) in the examination of the extrahepatic bile
      ducts in patients with congenital bile duct dilatation. METHODS: Intraductal US
      via a transpapillary route was used in consecutive patients with congenital bile
      duct dilatation. A 2.0 mm diameter, 20 MHz frequency catheter probe was used. The
      images were correlated with the results of histologic examination of the
      resection specimens. RESULTS: Intraductal US was performed successfully via the
      transpapillary route in 8 of 10 patients. In the other 2 patients, the
      percutaneous transhepatic route was used. In the 6 patients with cylindrical
      dilatation, intraductal US demonstrated the entire extrahepatic bile duct. In 1
      patient, it showed a bile duct cancer not demonstrated by cholangiography. In 2
      of the 4 patients with cystic dilatation, intraductal US did not demonstrate the
      entire extrahepatic bile duct because of the low penetration depth of the probe.
      Percutaneous transhepatic cholangioscopy was required in these patients.
      CONCLUSIONS: Intraductal US is useful for demonstrating cancers in the
      extrahepatic bile ducts in patients with congenital cylindrical ductal
      dilatation.

PMID- 10202065
TI  - Gastric aberrant pancreas: EUS analysis in comparison with the histology.
AB  - BACKGROUND: Histologic diagnosis of aberrant pancreas is usually difficult when
      tissue samples are obtained with a standard biopsy forceps. The aim of this study
      was to describe the endosonographic (EUS) features of gastric aberrant pancreas.
      METHODS: EUS was performed in 10 patients with aberrant pancreas before
      resection. EUS features of the lesions were analyzed and compared with resected
      specimens retrospectively. RESULTS: EUS in 5 lesions (50%) demonstrated the
      ectopic pancreatic tissue as located in the third and fourth sonographic layers
      (submucosa and muscularis propria) and in the third layer (submucosa) in the
      other 5 lesions. The margin appeared for the most part indistinct (80%) because
      of the lobular structure of the acinous tissue. The internal echo pattern in all
      cases was heterogeneous, mainly a hypoechoic image (acinous tissue) accompanied
      by scattered small hyperechoic areas (adipose tissue). An anechoic area (duct
      dilatation) (80%) and fourth-layer thickening (muscular hypertrophy) (80%) were
      commonly visualized. CONCLUSION: Gastric aberrant pancreas has characteristic EUS
      features that correlate with specific histologic components and is variable with
      regard to sonographic layer of origin.

PMID- 10202066
TI  - Experience with staging laparoscopy in pancreatic malignancy.
AB  - BACKGROUND: The role of diagnostic laparoscopy in the staging of abdominal
      malignancies is not well defined. METHODS: We retrospectively reviewed the
      usefulness of diagnostic laparoscopy as a staging procedure in pancreatic
      malignancy. This experience between February 1988 and May 1997 involves 109 cases
      of suspected or proven pancreatic malignancy. All laparoscopies were performed
      with the patient under conscious sedation and local anesthesia in an endoscopy
      suite. RESULTS: Of the 109 patients with pancreatic cancer, 45 (42%) had
      metastatic disease. The use of computed tomography (CT) alone revealed the
      existence of liver metastases in 10 of 109 (9%) patients, which were confirmed
      laparoscopically. The further use of laparoscopy identified metastases in 29 more
      cases: hepatic, 23; hepatic and peritoneal, 3; peritoneal and mesenteric, 1; and
      mesenteric, 2. CT in conjunction with laparoscopy therefore revealed metastatic
      liver, peritoneal, or mesenteric lesions in 39 of 109 (36%) patients with
      pancreatic cancer. After staging laparoscopy, 67 of 69 patients underwent
      laparotomy. Metastatic disease was identified at laparotomy in 6 more patients;
      however, only 4 of these patients had metastases to the liver whereas 2 had
      metastases to the peripancreatic lymph nodes. Therefore, in patients with
      pancreatic malignancy, the negative predictive value for the diagnosis of
      metastases to the liver, peritoneum or mesentery was 94% (61 of 65 patients). The
      positive predictive value of laparoscopy alone for the detection of metastatic
      disease to the liver, peritoneum, or mesentery was 88% (29 of 33 patients).
      Laparoscopy was successfully performed without complications in all patients with
      pancreatic cancer; however, one had a technically unsatisfactory examination. The
      overall rate of resectability after staging by imaging studies and laparoscopy
      was 57% (35 of 61 patients). CONCLUSIONS: In patients with a negative CT for
      metastases, laparoscopic identification of metastases avoided unnecessary
      laparotomy in 29 of 99 (29%) patients with pancreatic cancer. Staging laparoscopy
      is indicated in all cases of pancreatic malignancy before an attempt at a
      surgical cure.

PMID- 10202067
TI  - Endoscopic Nd:YAG laser therapy for villous adenomas of the right colon.
AB  - BACKGROUND: Endoscopic laser therapy is considered an acceptable treatment of
      benign colorectal adenomas. The aim of our study was to evaluate the efficacy of
      Nd:YAG laser to ablate right-sided colonic sessile adenomas. METHODS: Between
      January 1990 and February 1996, 56 patients underwent laser therapy because of
      high operative risk or refusal of surgery. Lesions were located as follows: cecum
      (23), ascending, (15), and hepatic flexure (18). Six patients (10.7%) had
      multiple polyps in the ascending colon. Histologic examination showed a
      tubulovillous pattern in 20 (35.7%) and a villous pattern in 36 (64.3%). Low
      grade dysplasia was detected in 44 patients (78. 5%) and high-grade dysplasia in
      12 (21.4%). RESULTS: The number of laser sessions ranged between 1 and 6 (median
      3) and complete ablation, histologically confirmed, was achieved in 49 cases
      (87.5%). Seven patients (12.5%) underwent surgery: 2 for incomplete tumor
      destruction, 3 because of invasive carcinoma on repeated biopsies. Two patients
      (3.6%) had complications (one perforation of the cecum and one hemorrhage).
      Follow-up ranged from 6 to 60 months and no recurrences were observed.
      CONCLUSION: Laser therapy is an effective method for the destruction of sessile
      adenomas of the right colon in selected patients.

PMID- 10202069
TI  - Cameron erosions.

PMID- 10202068
TI  - Intralesional steroids augment the effects of endoscopic dilation in corrosive
      esophageal strictures.
AB  - BACKGROUND: Intralesional corticosteroid injection has been shown to be effective
      in refractory esophageal strictures of various etiologies. The present study was
      conducted to determine the efficacy of intralesional triamcinolone in augmenting
      results of endoscopic dilation in corrosive esophageal strictures. METHODS:
      Seventeen patients with corrosive esophageal strictures were treated with
      endoscopic dilation together with injection of triamcinolone acetonide into the
      stricture. Fourteen patients were already undergoing dilation; 3 patients were
      newly recruited. The interval between dilations and frequency of dilation were
      calculated before and after corticosteroid injections, and periodic dilation
      index was calculated as number of dilations/number of months. RESULTS: The mean
      age of the 17 patients (8 men and 9 women) was 30+/-9.21 (range 13 to 52).
      Thirteen had strictures due to acid ingestion, four to alkali ingestion. There
      were 18 strictures in total, involving the upper (n = 2), middle (n = 10), and
      lower (n = 6) thirds of esophagus. Fourteen patients already on a dilation
      program had undergone 27.92+/-28.63 (range 6 to 92) dilations over a period of
      22.92+/-30.73 months (range 2 to 96) before corticosteroid injections. Nine
      patients received a single injection of triamcinolone, whereas four each had two
      and three sessions. The dilation requirement after injections in these 14
      patients was reduced to 3.57+/-2.90 (range 0 to 10) dilations over a period of
      10.5+/-5.58 (range 4 to 21) months. The median total periodic dilation index
      irrespective of corticosteroid therapy was 0.33 (range 0.55 to 1.8). In 12 of the
      14 patients, periodic dilation index before injections (range 0.91 to 3.0, median
      1.67) was higher than the median total periodic dilation index and in all the 14
      patients periodic dilation index after corticosteroid therapy (range 0 to 0.83,
      median 0.32) was less than the median of total periodic dilation index (p <
      0.01). In addition three patients received intralesional corticosteroid
      injections at the time of first dilation. These three patients could be
      effectively dilated with 5, 3, and 3 dilations. CONCLUSIONS: Intralesional
      triamcinolone injections augment the effects of endoscopic dilation in patients
      with corrosive esophageal strictures.

PMID- 10202070
TI  - Argon beam coagulation for treatment of symptomatic radiation-induced proctitis.
AB  - BACKGROUND: Radiation proctitis is a complication of radiotherapy for malignant
      pelvic disease. Argon beam coagulation is a new and rapidly evolving technology
      that permits a "no-touch" electrocoagulation of diseased tissue. METHODS: We
      analyzed retrospectively the records of 7 patients with prostatic and endometrial
      cancers treated with irrradiation (median radiation dose was 6840 cGy, range 2400
      to 7200 cGy). The median time to onset of symptoms after the conclusion of
      radiotherapy was 20 months (range 16 to 48 months); symptoms consisted of rectal
      bleeding and tenesmus in all patients. The patients underwent argon beam
      coagulation after colonoscopic evaluation. The usual treatment interval was 3
      weeks (range 1 to 3 weeks). RESULTS: A median of 2 treatment sessions (range 2 to
      4) was necessary for complete symptom relief. All interventions were well
      tolerated without complications. During follow-up (median 24 months, range 18 to
      24 months), there was no recurrence of symptoms (bleeding, tenesmus).
      CONCLUSIONS: Argon beam coagulation is a safe, well tolerated, and effective
      treatment option in symptomatic radiation proctitis.

PMID- 10202071
TI  - Clinical usefulness of 3% hydrogen peroxide in acute upper GI bleeding: a pilot
      study.
AB  - BACKGROUND: A major problem in the endoscopic management of acute upper
      gastrointestinal (GI) bleeding is the presence of blood and clots overlying the
      bleeding source, preventing visualization of the lesion. A simple alternative is
      to alter the characteristics of blood such that it not only becomes easier to
      remove but also becomes translucent. We report the results of a pilot study on
      the use of hydrogen peroxide in patients with acute upper GI bleeding. METHODS:
      Patients with acute upper GI bleeding were studied if the presence of blood or
      clots obscured the site of bleeding. The potential site of bleeding was initially
      sprayed with 200 mL water and then with 200 mL 3% hydrogen peroxide mixed with
      simethicone. RESULTS: In 6 patients with acute upper GI bleeding, hydrogen
      peroxide spray resulted in good to excellent visualization of the bleeding
      source. Hemostasis occurred in 2 patients who were actively bleeding. There were
      no adverse effects or complications. CONCLUSIONS: Hydrogen peroxide significantly
      enhanced clot dissolution and endoscopic visualization in patients with acute
      upper GI bleeding.

PMID- 10202072
TI  - A novel clinical application for endoscopic mucosal clipping.
AB  - BACKGROUND: Endoscopic hemoclipping has been shown to be effective in the
      treatment of gastrointestinal bleeding. Here we describe a novel clinical
      application for endoscopic application of metal clips. METHODS: A middle-aged man
      with inoperable squamous cell cancer of the esophagus underwent per protocol a
      barium esophagogram to document tumor margins prior to radiation therapy. This
      study failed to localize the full extent of the tumor. At endoscopy, the tumor
      margins were clearly visible. To delineate the proximal and distal margins,
      detachable metallic clips were passed through the accessory channel of a standard
      endoscope and using a clip fixing device the clips were placed at each level.
      Subsequently, a chest x-ray was obtained. RESULTS: Placement of mucosal clips
      facilitated radiotherapy. CONCLUSIONS: Endoscopic mucosal clipping may serve as a
      useful technique for localizing or marking gastrointestinal lesions, especially
      for demarcating a precise radiation field when conventional techniques fail.

PMID- 10202073
TI  - Extraction of migrated self-expanding esophageal metal stents.
AB  - BACKGROUND: When self-expanding metal stents are used in the palliative treatment
      of malignant stenoses complications can occur and require the endoscopic
      extraction of the stent. METHODS: Three Gianturco-Z stents and two EsophaCoil
      stents had to be extracted because of migration (4 patients) and strangulation of
      healthy esophageal tissue between the coil loops during EsophaCoil stent release
      (1 patient). Because of the strong expansion force of the Gianturco-Z stent, the
      plastic sheath of a polypectomy snare was replaced by the steel sheath of a
      basket used for mechanical lithotripsy of bile duct stones. The sufficient
      resistance of the steel sheath allowed the stents to be compressed. The
      EsophaCoil stents were gradually retracted with a polypectomy snare over a
      plastic tube. RESULTS: All stents could be extracted successfully. There were no
      severe complications related to extraction. CONCLUSION: By means of the
      endoscopic extraction techniques described above, it is possible to safely remove
      self-expanding esophageal stents.

PMID- 10202074
TI  - Acute esophageal necrosis: report of two cases and a review of the literature.

PMID- 10202075
TI  - Pseudowatermelon esophagus as a consequence of endoscopic multiband ligation.

PMID- 10202076
TI  - Gastric mucosal heterotopia in the gastric submucosa: an evaluation by EUS.

PMID- 10202077
TI  - Small bowel obstruction resulting from mesenteric hematoma caused by spontaneous
      rupture of a jejunal branch artery.

PMID- 10202079
TI  - Use of intraoperative enteroscopy to diagnose nonsteroidal anti-inflammatory drug
      injury to the small intestine.

PMID- 10202078
TI  - Late migration of a self-expandable metal stent and successful endoscopic
      management.

PMID- 10202080
TI  - Gastrointestinal endoscopy 

PMID- 10202083
TI  - Complex patterns of food allocation in asynchronously hatching broods of crimson
      rosellas.
AB  - In birds, asynchronous hatching typically leads to lower growth and survival of
      last-hatched chicks. However, all crimson rosella Platycercus elegans, chicks
      grow at the same rate, although first-hatched chicks can be as much as seven
      times heavier than last-hatched chicks at the end of hatching. We examined the
      delivery and distribution of food to 18 rosella broods by videotaping feeds and
      simultaneously recording mass changes in the nestbox using a digital balance.
      Parents visited the nest infrequently and delivered loads of up to 25% of their
      body weight during a feeding visit. Male rosellas consistently delivered larger
      loads and consequently had higher feeding rates (g/h) than females. Parents
      distributed food between chicks by direct regurgitation in a series of up to 51
      food transfers. Overall, chicks of all hatching ranks received equal numbers of
      transfers, but parents differed in how they distributed food within the brood.
      Males fed first-hatched chicks more than last-hatched chicks, whereas females
      distributed food equally to all chicks. Selective feeding of small chicks might
      be costly to females since they delivered food more slowly than males and spent
      more time in the nestbox. Thus female rosellas may invest more in current
      reproduction than males. Parents also distributed food differently to male and
      female chicks. Large males were fed more than all other nestlings, while female
      nestlings were fed equally irrespective of size. This study confirms that complex
      patterns of parental allocation occur in wild populations. Copyright 1999 The
      Association for the Study of Animal Behaviour.

PMID- 10202084
TI  - Urinary chemical cues affect light avoidance behaviour in male laboratory mice,
      Mus musculus.
AB  - Chemical signals from conspecifics can influence the behaviour and neuroendocrine
      axis of mice. Several different molecules are excreted with urine, depending on
      hormonal level, and can indicate the sex of the emitter. In male mice, these
      chemicals are the major urinary proteins (MUPs) and some small volatile odorant
      molecues that are found bound to them. We tested adult males for light avoidance
      behaviour in a two-chamber apparatus, with one light and one dark side, in the
      presence or absence of male urinary substances. The presence of chemical cues on
      either side of the cage was expected to modify light avoidance behaviour. The
      volatiles released from purified MUPs had the same effect as whole adult male
      urine, in that they induced a faster onset of exploration of the light
      compartment. The results show that mice can use the information carried by the
      odorant molecules released by MUPs to recognize the urine of male mice, and
      respond appropriately. Copyright 1999 The Association for the Study of Animal
      Behaviour.

PMID- 10202085
TI  - The influence of nutritional state on shoal choice in zebrafish, Danio rerio.
AB  - We investigated the mechanisms and functions of shoal choice in relation to
      nutritional state in the zebrafish. Single fish that had been well fed or food
      deprived for 2 days were presented with a choice between two stimulus shoals.
      Food-deprived test fish showed a significant preference for well-fed stimulus
      fish over food-deprived ones whereas well-fed test fish did not exhibit any
      significant preference. Subsequent experiments showed that food-deprived test
      fish had a significantly higher foraging success in shoals consisting of well-fed
      individuals than in ones that comprised food-deprived fish. No difference in the
      locomotory behaviour of food-deprived and well-fed stimulus fish was found with
      respect to the proportion of time spent swimming (as opposed to being
      motionless), the proportion of time spent in the upper part of the test tank and
      the number of sharp turns. However, body weight, stomach width (measured directly
      behind the pectoral girdle) and ventro-dorsal height significantly decreased over
      a 48-h food-deprivation period. The potential use of the latter factors for the
      recognition of food-deprived individuals is discussed. Copyright 1999 The
      Association for the Study of Animal Behaviour.

PMID- 10202086
TI  - Male-male competition and female choice in brown trout.
AB  - In some salmonid species, the females have been assumed to choose their mates on
      the size of the male's adipose fin. This hypothesis was tested in a stream water
      aquarium, in which 19 brown trout, Salmo trutta, females were allowed to choose
      between two males of the same body size but with different adipose fin sizes. The
      two males were separated from each other in cages. After the female had started
      to prepare her nest close to one of them, the males were released and allowed to
      fight each other for the opportunity to spawn. Out of 19 females, 14 prepared a
      nest closest to the male with the larger adipose fin. However, only six of the 14
      females spawned with this male. Males that spawned were more dominant (i.e. were
      more likely to win fights). When the female spawned with the male she chose, he
      was less aggressive towards her than when she spawned with the other male. There
      were no significant differences in the plasma levels of testosterone (T) and 11
      ketotestosterone (11-KT) between the chosen males and those not chosen. However,
      the dominant males had significantly higher plasma levels of T and 11-KT both
      before and after the experiment. The results support the view that female brown
      trout exhibit mate choice, but their choice is overruled by male-male
      competition. Copyright 1999 The Association for the Study of Animal Behaviour.

PMID- 10202087
TI  - Social learning in common ravens, Corvus corax.
AB  - We conducted an experiment to investigate whether the presence of a conspecific
      model can promote the acquisition of a motor task in common ravens. For this
      purpose, dyads, either of control birds or of model-observer pairings, were
      allowed to operate together in an arena with a set of identical boxes. Each box
      consisted of two compartments each containing a reward of three pieces of meat.
      The compartments were closed by gliding lids with red flaps on their front,
      opening horizontally in opposite directions. Naive control individuals opened the
      lids exclusively by levering, that is, jumping on top of the box, inserting the
      beak at the posterior rim of the lid and pushing it open. Models were trained to
      demonstrate an alternative opening technique, pulling at the front flap, then
      jumping on top of the box to get at the reward. In contrast to the control birds,
      observers initially opened boxes both ways, by pulling and levering. Furthermore,
      observers approached the boxes more quickly and showed less fearful behaviour
      than the control birds, which we attribute to the enhancing effect of the model.
      We discuss both stimulus enhancement and motor imitation as possible learning
      mechanisms. Even though observers initially obtained a considerable amount of
      reward produced by the models, scrounging evidently did not inhibit learning.
      Copyright 1999 The Association for the Study of Animal Behaviour.

PMID- 10202088
TI  - Optimal copula duration in yellow dung flies: effects of female size and egg
      content.
AB  - We examine data on copula duration in dung flies, Scatophaga stercoraria, in
      relation to female phenotype. We use a marginal value theorem approach based on
      the plausible mechanisms of sperm competition to predict the effect of female
      variation on optimal copula duration, t *, from the male perspective. Future
      fertilizations are expected to have a trivial effect on t * with fully gravid
      females, but an increasing relative effect on t * towards completion of
      oviposition. t * is expected to be affected by female size because of variation
      in (1) a female's egg content, which increases the maximum egg gain available
      from a mating, and (2) the female reproductive tract, which affects the rate at
      which sperm are displaced. In fully gravid females, t * was not dependent on egg
      number variation, but showed a positive relation with egg content in females that
      had laid a varying proportion of their mature egg load at the time of mating, and
      were therefore not fully gravid. Our models predict that if a male can estimate
      egg content only by the distension of a female's abdomen, t * should increase in
      a similar way to that seen with 'take-over' females. We predict t * for fully
      gravid females by assuming that males can monitor female size. The data showed
      that sperm displacement rate decreased, and average egg content increased, with
      female size. Under two models for a sperm displacement mechanism, one (which
      assumes indirect displacement at a rate proportional to the increase in
      spermathecal volume) predicts the observed relation between t * and female size
      almost exactly. Small males copulated for longer than large males (as predicted
      and reported previously). Copyright 1999 The Association for the Study of Animal
      Behaviour.

PMID- 10202089
TI  - To split behaviour into bouts, log-transform the intervals.
AB  - Analysis of behaviour that is displayed in bouts depends crucially on
      quantitative estimates of bout criteria, that is, the lengths of the shortest
      intervals between bouts. Current methods estimate bout criteria by modelling the
      log-transformed (cumulative) frequency distributions of intervals between events.
      For analysis of feeding behaviour, these models will not result in biologically
      meaningful quantitative estimates (Tolkamp et al. 1998, Journal of Theoretical
      Biology194, 235-250). We proposed a method that models the frequency distribution
      of log-transformed interval lengths instead. Applying this method to a single
      data set showed that the log-transformed lengths of intervals between feeding
      events were distributed as two Gaussians. Here we test this model using a data
      set of 35 171 intervals between feeding that was obtained during an experiment
      with 38 cows in three dietary treatment groups. No meaningful bout criterion
      could be obtained for some individuals, which casts doubt on the general validity
      of the proposed model. Addition of a third log-normal improved the fit of the
      model and we hypothesized that this third population represents intervals
      including drinking. In a second experiment, we found the measurements to be
      consistent with this hypothesis. We obtained meaningful meal criteria for all
      individuals by fitting either a double, or a triple, log-normal model to the
      frequency distributions of the lengths of intervals between feeding. These log
      normal models appear to be not only more biologically meaningful than log
      (cumulative) frequency models but also far more flexible. Copyright 1999 The
      Association for the Study of Animal Behaviour.

PMID- 10202090
TI  - Noctuid moths show neural and behavioural responses to sounds made by some bat
      marking rings.
AB  - Coloured rings are often used for marking bats so that specific individuals can
      be recognized. We noticed that the rings of mouse-eared bats, Myotis myotis and
      Myotis blythii, in a combination of one plastic-split and one metallic ring on
      the same forearm, emitted sounds that were largely ultrasonic each time the rings
      met in flight. We recorded the ring sounds and the echolocation calls produced by
      the bats, and played them back to neural preparations of lesser yellow underwing
      moths, Noctua comes, while making extracellular recordings from the moths' A1
      auditory receptors. The peak energy of the ring sounds occurred much closer in
      frequency to the moth's best auditory frequency (the frequency at which the moth
      has the lowest auditory threshold) than the peak energy of the calls, for both
      bat species, and the ring sounds were detected at a threshold 5-6 dB peSPL lower
      than the calls. Moths performed evasive manoeuvres to playbacks of ring sounds
      more frequently than they did to control (tape noise) sequences. These neural and
      behavioural responses imply that certain bats should not be marked with two rings
      on one wing, as this may make the bat more apparent to tympanate insects, and may
      therefore reduce its foraging success. Copyright 1999 The Association for the
      Study of Animal Behaviour.

PMID- 10202091
TI  - Song learning from playback in zebra finches: is there an effect of operant
      contingency?
AB  - Social interaction is often regarded as crucial for song copying in zebra
      finches, Taeniopygia guttata. Contingencies in the interaction between pupil and
      tutor might be essential for the song-copying process. The effect of contingency
      between a pupil's operant behaviour and tutor song has been studied previously,
      but with contradictory results. Our aim in this experiment was to provide a more
      rigorous test of the effect of operant contingent exposure to song playback in
      zebra finches. Eight experimental males were trained to expose themselves to
      tutor song by operant key pecking during their sensitive phase for song learning.
      Each bird had a yoked control, which heard the same tutor song at the same time.
      All birds were acoustically isolated. The results were surprising in two ways:
      (1) the control birds copied song to which they were passively exposed; and (2)
      the experimental birds did not copy more than the controls did. So, we found no
      effect of operant contingency on song learning. Furthermore, when tested as
      adults all but one male preferred the tutor song to an unfamiliar one. We
      conclude that zebra finches can copy playback song, and that social interaction
      is not crucial for song copying, although it might still be facilitating.
      Copyright 1999 The Association for the Study of Animal Behaviour.

PMID- 10202092
TI  - Male choice, willingness to mate and body size in seaweed flies (Diptera:
      Coelopidae).
AB  - The mating system of seaweed flies is characterized by scramble competition and a
      premating struggle during which females vigorously attempt to remove mounted
      males and prevent copulation. Here we investigate factors affecting the
      willingness of males to mate in five species of Coelopa : C. frigida, C.
      nebularum, C. ursina, C. pilipes and C. vanduzeei. The data from 2000 individual
      observations of pairs of flies revealed no association between female size and
      the willingness of males to mate, suggesting that males do not exhibit mate
      choice for larger, more fecund females. Male willingness to mount was associated
      with male size in C. frigida, C. nebularum and C. ursina, although not in C.
      pilipes and C. vanduzeei. There is considerable intraspecific variation in male
      size in the former three species, including the presence of two almost discrete
      size classes within C. nebularum. We suggest that males of different sizes in
      these species may be adopting alternative reproductive strategies. Large males
      may benefit from increased longevity and their ability to withstand female
      rejection responses, whereas small males are more active and thus likely to
      encounter and mount more females. In addition small males develop faster and thus
      gain earlier access to females. Copyright 1999 The Association for the Study of
      Animal Behaviour.

PMID- 10202093
TI  - Sedentary life style of Neotropical sedge wrens promotes song imitation.
AB  - To what extent has the style of song development among songbirds coevolved with
      other life history strategies? Among Cistothorus wrens in North America, it seems
      that sedentary or site-faithful habits of marsh wrens, C. palustris, favour song
      imitation, but seminomadic habits of sedge wrens, C. platensis, favour song
      improvisation, whereby each male generates a large but unique song repertoire. In
      this study, we tested whether more sedentary populations of sedge wrens in the
      Neotropics would imitate songs. At our primary study site near Cartago, Costa
      Rica, breeding birds were colour-banded during 1995 and 1996, and follow-up
      surveys revealed that the birds remained at this site the year round. Extensive
      tape recording and analysis of songs showed that males had large song repertoires
      (200-300+ songs), and that many songs were shared among neighbouring males. In
      addition, males only 27 km distant, at La Pastora, used different songs.
      Furthermore, matched countersinging, in which two males answer each other with
      identical song types, was recorded near Brasilia, in Brazil. The sharing of songs
      among permanent neighbours, microgeographical variation in song, and matched
      countersinging can be achieved only through song imitation, thus revealing a
      striking difference in the style of song development among different populations
      of the sedge wren. In the Neotropics, having predictable neighbours throughout
      life appears to have favoured song imitation, so that individuals can interact
      using a common, learned code typical of the local population; among more mobile
      populations in North America, however, individuals improvise large repertoires of
      species-typical songs, thereby enabling singing males to communicate with any
      individual, no matter what the population of origin. Strategies of song
      development must correlate with life history features, and further surveys are
      needed to make sense of the great diversity of singing behaviours among
      songbirds. Copyright 1999 The Association for the Study of Animal Behaviour.

PMID- 10202094
TI  - Female responses to isolated signals from multimodal male courtship displays in
      the wolf spider genus Schizocosa (Araneae: Lycosidae).
AB  - Male wolf spiders within the genus Schizocosa display considerable variation in
      foreleg ornamentation as well as in courtship communication. Multiple modes of
      male signalling have evolved in a number of species. Divergence in courtship
      signals among species within this genus may be directly associated with variation
      in the sensory sensitivities of conspecific females. We isolated the visual and
      vibratory courtship cues of four species of Schizocosa and recorded conspecific
      female receptivity to each isolated cue. We also examined female receptivity to
      complete multimodal courtship signals. We found that the sensory sensitivities of
      conspecific females were associated with the predominant modes of male courtship
      communication. Species in which females use mostly stridulatory cues in assessing
      conspecific males tended to have stridulation-based male courtship displays (S.
      duplex and S. uetzi) while the opposite was true for species in which females
      used more visual cues in male assessment (S. stridulans and S. crassipes). This
      study suggests coevolution between male signal design and female sensory design.
      We discuss possible scenarios that could be driving this coevolution, including
      hypotheses of sensory bias and environmental constraints. Copyright 1999 The
      Association for the Study of Animal Behaviour.

PMID- 10202095
TI  - Parental provisioning, nestling departure decisions and prefledging mass
      recession in Cassin's auklets.
AB  - We investigated how parental provisioning and nestling departure behaviour
      interact to produce prefledging mass recession in Cassin's auklets, Ptychoramphus
      aleuticus. Under our hypothesis, auklet parents are reluctant provisioners and
      should be increasingly likely to terminate or reduce provisioning of their single
      nestling as it matures. For the nestling, remaining in the nest presents a risk
      of losing mass (if the parent does not provision) but also a possibility of
      additional provisioning. As the nestling matures and becomes increasingly capable
      of independence, the benefits of remaining in the nest decrease and nestlings
      should be increasingly likely to fledge. Nestlings also should be more likely to
      fledge when the expectation of additional provisioning is low. Data on parental
      provisioning (based on growth increments) and nestling departure were consistent
      with our hypothesis. Older and heavier nestlings had smaller growth increments
      than younger and lighter nestlings, suggesting that parents were reluctant to
      provision old and heavy nestlings. Older and heavier nestlings also were
      increasingly likely to fledge. We hypothesized that nestlings might use the
      intensity of mass loss to gauge parental reluctance to provision, and
      accordingly, nestlings were increasingly likely to fledge after experiencing a
      greater amount of mass loss. Copyright 1999 The Association for the Study of
      Animal Behaviour.

PMID- 10202096
TI  - Effects of social status on the dispersal behaviour of juvenile western screech
      owls.
AB  - Variation in timing and distance of dispersal movements of juvenile birds may
      result from differences in competitive ability. Dispersal by low-ranking
      juveniles may be initiated before dominants if the latter force subordinate
      siblings from natal areas. Conversely, when vacant territories are limited and
      are acquired on a first-come first-served basis, selection could operate on young
      to disperse as early as possible. In this case, dominant individuals with
      priority of access to resources in the natal area will mature more quickly and
      are expected to disperse first. If costs of dispersal increase with dispersal
      distance, dominant juveniles are expected to disperse shorter distances.
      Alternately, if there are advantages to long-distance dispersal, then dominants,
      which are in better condition, should disperse further than subordinates. We
      examined effects of social rank on the timing and distance (to wintering area) of
      dispersal movements by juvenile western screech-owls, Otus kennicottii, in
      southwestern Idaho. Based on observations of aggressive interactions made using
      video cameras attached to nestboxes, we assigned dominance ranks to nestlings
      within nine broods. We radiotracked young throughout the postfledging period to
      determine order of dispersal, and we located them after leaving their natal areas
      to determine distances to apparent overwintering areas. In six of seven broods,
      for which dispersal information could be recorded, the most dominant juvenile
      dispersed first. Moreover, in five of seven broods, the least dominant individual
      was the last individual to disperse, and the order of dispersal matched the
      dominance hierarchy in four of seven broods. In contrast, social status did not
      affect postfledging dispersal distance. We conclude that social dominance
      relationships influenced the timing of dispersal in juvenile western screech-owls
      but not distance travelled to overwinter sites. Copyright 1999 The Association
      for the Study of Animal Behaviour.

PMID- 10202097
TI  - The effect of predation on begging-call evolution in nestling wood warblers.
AB  - I combined a comparative study of begging in ground- and tree-nesting wood
      warblers (Parulidae) with experimental measures of the predation costs of warbler
      begging calls. Throughout their development, ground-nesting warbler nestlings had
      significantly higher-frequency begging calls than did tree-nesting warblers.
      There was also a trend for ground-nesting birds to have less rapidly modulated
      calls. There were no consistent associations between nesting site and the
      amplitude of the calls. Using miniature walkie-talkies hidden inside artificial
      nests, I reciprocally transplanted the begging calls of 5- and 8-day-old black
      throated blue warblers, Dendroica caerulescens (tree-nesting) and ovenbirds,
      Seiurus aurocapillus (ground-nesting) and measured the corresponding changes in
      rates of nest predation. For the begging calls of 8-day-old nestlings, but not
      those of 5-day-olds, the calls of the tree-nesting species coming from ground
      nests incurred greater costs than did the calls of ground nesters. The reciprocal
      transplant had little effect on the rate of predation. Tooth imprints on clay
      eggs placed in artificial nests indicated that eastern chipmunks, Tamias
      striatus, were responsible for the increased cost of begging for black-throated
      blue calls coming from the ground. These data suggest that nest predation may be
      responsible for maintaining some of the interspecific differences in the acoustic
      structure of begging calls. Copyright 1999 The Association for the Study of
      Animal Behaviour.

PMID- 10202098
TI  - The winner and loser effect: integrating multiple experiences.
AB  - An important question in state-dependent behaviour is how multiple influences on
      state are integrated to determine current behaviour. Aggressive behaviour is
      known to be affected by a prior contest experience. Nevertheless, whether and how
      multiple prior fighting experiences are integrated into a fighting decision
      remain unexplored. In this study, individuals of Rivulus marmoratus
      (Cyprinodontidae), a hermaphroditic fish, were given different combinations of
      two prior fighting experiences to investigate: (1) the effect of penultimate
      experiences on the probability of winning a subsequent contest; (2) the relative
      effect of a recent win and loss; and (3) whether the effect of a winning
      experience was as short lived as observed in other species. Penultimate and
      recent fighting experiences were given to the test fish approximately 48 and 24 h
      prior to the dyadic contests, respectively. From the results of the five types of
      contests staged, we conclude that: (1) penultimate fighting experiences had a
      significant effect on the probability of winning a subsequent contest; (2) a more
      recent experience had a more pronounced effect than an earlier experience, which
      suggested that the effect of a fighting experience would decay and/or the effect
      of a recent experience would interfere with the effect of an earlier experience;
      (3) no asymmetric effect between a winning experience and a losing experience was
      detected; and (4) the effect of both a winning and a losing experience lasted for
      at least 48 h in R. marmoratus which was the maximum time tested in these
      experiments. The possible reasons for the differences in results among studies of
      experience effects on contest outcomes are discussed. Copyright 1999 The
      Association for the Study of Animal Behaviour.

PMID- 10202099
TI  - Infant handling in wild Cebus capucinus: testing bonds between females?
AB  - The evolved functions, if any, of infant handling (IH) by female primates remain
      unclear for many species. I tested a new hypothesis, that IH tests social bonds
      between adult females, using data on a group of wild white-faced capuchins. I
      also tested the nonadaptive, learning-to-mother, reciprocity, harassment and
      alliance-formation hypotheses. Focal subjects were the mothers of 10 infants that
      ranged in age from 0 to 90 days. The behaviours comprising IH (inspecting,
      nuzzling, sniffing, and a distinctive vocalization) differed from typical
      maternal behaviour. Nulliparous females engaged in no more IH than did parous
      females. The median frequency of rough handling was zero, kidnapping was not
      observed, and maternal restraint of infants was extremely rare. Infant handling
      rate was unrelated to the relative dominance ranks of the mother and the handler.
      Females tended to handle the infants of females with which they groomed and
      formed aggressive coalitions more frequently. Dyadic IH rates were not correlated
      with rates of allonursing when the infants were older than 90 days of age. There
      was no evidence for reciprocal exchanges of IH between females. Mother-terminated
      IH bouts were longer when the mother had groomed the handler more frequently
      before the infant's birth. Based on these findings, the learning-to-mother,
      reciprocity and harassment hypotheses are unsupported for this species. Some
      support exists for the nonadaptive hypothesis. Contrasting predictions of the
      bond-testing and alliance-formation hypothesis are presented for future testing.
      Copyright 1999 The Association for the Study of Animal Behaviour.

PMID- 10202100
TI  - Season- and size-dependent risk taking in juvenile coho salmon: experimental
      evaluation of asset protection.
AB  - Using juvenile coho salmon, Oncorhynchus kisutch, we tested predictions arising
      from dynamic optimization models of foraging under predation risk. Coho juveniles
      from two size groups raised in the laboratory were individually fed varying food
      rations. Their willingness to risk predation was measured as the time to resume
      foraging after presentation of a predator model. Small fish (mean weight 1.5 g)
      resumed feeding earlier than larger fish (3.5 g) as predicted by dynamic models
      under summer photoperiod but not under autumn photoperiod. Contrary to
      predictions, larger fish did not increase risk taking and small fish decreased
      risk taking between summer and autumn treatments. Food ration significantly
      influenced time to resume feeding only in small coho. A simple mechanistic model
      we proposed to explain feeding motivation under risk as a function of body size
      and prior growth rate was not sufficient to explain observed variation in risk
      taking. This study suggests that coho salmon use photoperiod and their own body
      size as cues for long-term, state-dependent adjustments of feeding behaviour. The
      lower risk taking of larger fish is probably an example of asset protection,
      whereby larger animals accept less predation risk to protect their greater
      accumulated fitness value. The decrease of risk taking in small fish in the
      autumn was possibly caused by a switch of life history trajectory towards delayed
      smolting. Copyright 1999 The Association for the Study of Animal Behaviour.

PMID- 10202101
TI  - Behavioural patterns associated with faecal cortisol levels in free-ranging
      female ring-tailed lemurs, Lemur catta.
AB  - The study of physiological stress and its context in free-ranging animals
      provides a means for understanding the challenges found in the natural habitat.
      Patterns of physiological stress in free-ranging animals have yet to be well
      characterized. Methodological difficulties in measuring physiological responses
      in the natural habitat have limited this area of research. In this research,
      physiological stress in free-ranging ring-tailed lemurs, Lemur catta, was
      estimated using a steroid-extraction method to measure cortisol levels from
      female faeces. Ten females were observed across two social groups in southwestern
      Madagascar during a 5-month period including portions of the annual wet and dry
      seasons. I used behavioural measures to estimate predation threat, food
      accessibility and individual dominance status, to determine whether these
      variables predict faecal cortisol levels. Faecal cortisol levels were relatively
      high during two distinct periods: one period coincided with late gestation and
      the other period corresponded with the end of the dry season, when high-intensity
      antipredatory behaviour and estimates of feeding effort were elevated. In
      addition, faecal cortisol measures were significantly correlated with dominance
      indices: high-index individuals had high cortisol values, and low-index
      individuals had low cortisol values. These results suggest that faecal cortisol
      measures can be used to assess seasonal and individual differences in adrenal
      activity in this lemurid primate, and that this measure could provide a means for
      quantifying physiological stress in free-ranging animals. Copyright 1999 The
      Association for the Study of Animal Behaviour.

PMID- 10202102
TI  - Phylogenetic influence on mating call preferences in female tungara frogs,
      Physalaemus pustulosus.
AB  - We evaluated how various phylogenetic models for estimating ancestral characters
      can influence studies of behavioural evolution. Previously we used a single model
      of evolution to estimate the values of call characters at ancestral nodes for the
      Physalaemus pustulosus species group and some close relatives (Ryan & Rand 1995,
      Science, 269, 390-392). We then synthesized these ancestral calls and measured
      the females' responses to such calls in phonotaxis experiments. We repeated the
      above procedure to determine the sensitivity of these results and conclusions to
      various models used to estimate the ancestral call characters. We asked whether:
      (1) different models gave different call estimates for the same nodes; (2)
      different call estimates at the same node were perceived as different by females;
      and (3) differences in female responses influenced previous conclusions. We used
      seven different models that varied in at least one of the following parameters:
      tree topology (bifurcating versus pectinate in-group trees), algorithms (local
      squared-change versus squared-change parsimony), tempo (gradual or punctuated
      evolution), and outgroups (two or three outgroup taxa used). Although different
      models often gave different call estimates for the same node, these different
      estimates often were not perceived as different by the females. These data
      reinforce our previous conclusions that: (1) the range of female preferences
      exceeds the known variation of the conspecific call; (2) females do not
      discriminate between the conspecific call and the call of their most recent
      ancestor; and (3) female responses may be context dependent, given that females
      differ in their responses to the same signal variation in discrimination and
      recognition experiments. Copyright 1999 The Association for the Study of Animal
      Behaviour.

PMID- 10202103
TI  - Leg autotomy in a spider has minimal costs in competitive ability and
      development.
AB  - A number of species have the ability to autotomize limbs voluntarily, but animals
      that have lost limbs often face substantial costs. We examined the frequency of
      leg loss and its effects on competitive ability and development in the spider
      Holocnemus pluchei (Araneae: Pholcidae), a family of spiders known for its
      readiness to autotomize legs. Leg loss was common in field populations, with 7.5%
      of all surveyed spiders missing at least one leg, most commonly one of the
      anterior pair. More spiders were missing multiple legs than expected by chance,
      suggesting that leg loss events are not independent. Large adult spiders were
      missing legs more frequently than were small spiders. The competitive ability of
      injured males was tested in three contexts. In the field, no effect of leg loss
      was found on the ability of spiders to remain in webs into which they were
      introduced. In the laboratory, no effect of leg loss was found on the ability to
      fight with a single opponent over a prey, except that injured spiders were more
      likely to lose high-intensity fights. There was no difference between intact and
      injured males in their ability to compete with three females for limited prey.
      Leg loss significantly affected development time. The moult interval during the
      instar in which the injury occurred increased by approximately 15%. However, the
      growth rate for injured spiders was slightly but not significantly faster in the
      instar following leg loss, and total development time of the two instars together
      did not differ significantly between treatments. No spider showed any signs of
      regeneration. We conclude that, although there were some statistically
      significant differences between intact and injured males, these are unlikely to
      have major impacts on fitness, in contrast to findings in other species.
      Copyright 1999 The Association for the Study of Animal Behaviour.

PMID- 10202104
TI  - Metabolic costs of heat solicitation calls in relation to thermal need in embryos
      of American white pelicans.
AB  - Chilled embryos of pelicans, Pelecanus erythrorhynchos, begin to vocally solicit
      parental heat at the pipped-egg stage. Honest signalling models predict that if
      vocal heat solicitation is a true reflection of need, then solicitation should be
      costly and costs should increase with the embryo's need for warmth. Using open
      flow respirometry, we measured the metabolic costs associated with vocal heat
      solicitation by exposing embryos to either a decreasing or increasing series of
      body temperatures, ranging from 25 to 37.8 degrees C. We measured baseline costs
      (stable temperature, embryo silent) and costs associated with cold-induced
      calling at each temperature. At natural incubation temperature (37.8 degrees C),
      call rates and costs associated with calling were negligible, as was thermal
      need. Metabolic costs relative to baseline costs and costs per call increased
      with thermal need as body temperature declined. Absolute metabolic costs
      increased between 37.8 and 35 degrees C, then remained stable down to 25 degrees
      C. Call rates increased as embryos were chilled within the range of temperatures
      most frequently experienced in nature (35-37.8 degrees C), then decreased
      significantly for all lower temperatures, probably owing to reduced overall
      metabolic rate at lower temperatures (25-37.8 degrees C). The results generally
      support the honest signalling prediction that vocal heat solicitation is
      metabolically costly, and that costs increase with need. Copyright 1999 The
      Association for the Study of Animal Behaviour.

PMID- 10202105
TI  - Interpopulation and context-related differences in responses of a marine
      gastropod to predation risk.
AB  - We conducted laboratory experiments to investigate interpopulation differences in
      the behavioural responses of the whelk Buccinum undatum to the predatory lobster
      Homarus americanus and the asteroid Leptasterias polaris, both in the absence and
      presence of feeding opportunities. Whelks from three populations in the eastern
      North Atlantic (1) responded to lobsters by displaying avoidance behaviours
      (burrowing in the sediments or retreating inside their shell), (2) responded to
      asteroids by displaying escape responses (rapid crawling, shell rocking behaviour
      or foot contortions), and (3) more often refrained from feeding in the presence
      of a lobster than in the presence of an asteroid. Although whelks from the three
      populations responded similarly to lobsters and asteroids, interpopulation
      differences were evident. Thus, whelks from populations sympatric with a given
      predator more frequently displayed 'appropriate' antipredator behaviours (i.e.
      avoidance in the presence of a lobster, and escape in the presence of an
      asteroid) than did whelks allopatric with that predator. Also, whelks from a
      population sympatric with both predators fed less readily in the presence of a
      given predator than did whelks allopatric with that predator. However, the
      presence of a lobster or an asteroid had the same impact on the feeding response
      of whelks from two populations with contrasting predator fields, one sympatric
      with lobsters, but allopatric with asteroids, and one sympatric with asteroids,
      but allopatric with lobsters. The results of our study indicate that coexistence
      (over evolutionary or ecological time) with lobsters and asteroids increases the
      propensity of the whelk to display avoidance and escape behaviours in the
      presence of lobsters and asteroids, respectively, but has a less predictable
      effect on how whelks trade off predation risk and food acquisition. Studies are
      needed to investigate the roles of inheritance and experience on the development
      of antipredator behaviours and decision making by prey animals when predation
      risk conflicts with other fitness-related activities such as the acquisition of
      food or reproductive opportunities. Copyright 1999 The Association for the Study
      of Animal Behaviour.

PMID- 10202107
TI  - Rapid expression of IL-1beta by intestinal epithelial cells in vitro.
AB  - Intestinal epithelial cells have been shown to produce IL-1beta in vivo. This
      gene expression is rapid and precedes most determinants of inflammation,
      suggesting a pivotal role for IL-1beta in the early events leading to
      inflammation. To better understand the mechanisms leading to this IL-1beta
      production, we have developed an in vitro model system employing a nontransformed
      intestinal epithelial cell line that does not constitutively express IL-1beta.
      Following detachment, these cells rapidly expressed IL-1beta mRNA. This
      expression was enhanced, but not induced, by LPS. IL-1beta protein was detected
      by immunoprecipitation in the culture medium from passaged IEC-18 but not
      intracellularly, suggesting an efficient secretion of the molecule following
      induction. Interestingly, culture supernatants from passaged cells were without
      IL-1 bioactivity, suggesting the presence of an inhibitor as well. RT-PCR and
      Western blot analysis showed expression of IL-1RII by IEC-18 following
      detachment, possibly explaining the observed lack of bioactivity. These results
      indicate a novel pathway for IL-1beta production and suggest that proinflammatory
      effects of IEC-derived IL-1 may be modulated by the simultaneous production of IL
      1 antagonists.

PMID- 10202109
TI  - A role for CD99 in T cell activation.
AB  - The function of the T cell surface protein CD99 was investigated in human CD4(+)
      peripheral T cells. Crosslinking of the CD99 molecule using anti-CD99 mAbs in the
      presence of anti-CD3 Ab resulted in a marked enhancement of proliferation. CD99
      coligation also enhanced CD25 expression and early markers of T cell activation,
      CD69 and CD40L. Ligation of CD99 resulted in the pronounced tyrosine
      phosphorylation of an approximately 29-kDa protein suggesting that a specific
      CD99-induced signal transduction pathway may exist. Simultaneous costimulation
      with anti-CD99 and anti-CD28 Abs appeared to have additive effects on CD40L
      expression while CD99 ligation had no effect on CD2-mediated T cell induction of
      CD40L expression. These results demonstrate that CD99 signal transduction can
      deliver effective costimulatory signals to T cells.

PMID- 10202108
TI  - Role of TNF-alpha in the induction of fungicidal activity of mouse peritoneal
      exudate cells against Cryptococcus neoformans by IL-12 and IL-18.
AB  - We have recently demonstrated that two IFN-gamma-inducing cytokines, interleukin
      (IL)-12 and IL-18, synergistically induced the fungicidal activity of mouse
      peritoneal exudate cells (PEC) against Cryptococcus neoformans through NK cell
      production of interferon (IFN)-gamma and nitric oxide (NO) synthesis. In the
      present study, we further dissected these effects by examining the involvement of
      tumor necrosis factor (TNF)-alpha in the induction of IL-12/IL-18-stimulated PEC
      fungicidal activity. The addition of neutralizing anti-TNF-alpha mAb
      significantly suppressed IL-12/IL-18-stimulated PEC anticryptococcal activity.
      This effect was ascribed to the inhibition of macrophage NO synthesis, but not of
      IFN-gamma production by NK cells, because the same treatment inhibited the former
      response, but not the latter one. On the other hand, combined treatment with IL
      12 and IL-18 synergistically induced the production of TNF-alpha by PEC and this
      effect was almost completely abrogated by neutralizing anti-IFN-gamma mAb. The
      cell type producing TNF-alpha among PEC was mostly macrophage. TNF-alpha
      significantly promoted macrophage NO production and anticryptococcal activity
      induced by IFN-gamma, and furthermore anti-TNF-alpha mAb partially inhibited
      these responses. Considered together, our results indicated that TNF-alpha
      contributed to the potentiation of IL-12/IL-18-induced PEC fungicidal activity
      against C. neoformans through enhancement of IFN-gamma-induced production of NO
      by macrophages, but not through increased production of IFN-gamma by NK cells.

PMID- 10202110
TI  - Induction of apoptosis in activated T cell blasts by suppressive macrophages: a
      possible immunotherapeutic approach for treatment of autoimmune disease.
AB  - Large suppressive macrophages (LSM) were induced by restimulating spleen cells
      from rats with experimental autoimmune myasthenia gravis (EAMG) in vitro, with
      the autoantigen acetylcholine receptor (AChR) in the presence of cyclosporine A.
      LSM, purified from these cultures, are extremely potent suppressors of AChR
      stimulated lymphoproliferative responses and antibody responses in vitro. In the
      present study, we have analyzed the factors that determine susceptibility of
      primed lymph node cells (pLNC) to suppression by LSM and examined the fate of
      these cells. We found three characteristics of pLNC that influenced their
      susceptibility to suppression. First, pLNC were required to be activated (by
      antigen in these experiments) in order for suppression to occur. Resting
      lymphocytes were not affected, even when they were present in cultures where
      antigen-activated lymphoblasts were being actively suppressed. Second, antigen
      specificity of the responder cells influenced their susceptibility to suppression
      by LSM. AChR-specific cells were relatively more susceptible to suppression by
      AChR-induced LSM than pLNC primed to an unrelated antigen, keyhole limpet
      hemocyanin. Third, T cell proliferation was suppressed by LSM to a far greater
      extent than antibody production by B cells. Using enriched T cell blasts
      generated from AChR-stimulated T cell lines, we found that LSM rapidly suppressed
      [3H]TdR uptake and induced DNA fragmentation assessed by the TUNEL assay (within
      8 h of coculture) and induced morphological signs of apoptosis of T cells (within
      24 h). Few, if any, blasts remained by 48 h of coculture. The ability to suppress
      an activated immune response permanently, without affecting nonactivated,
      bystander lymphocytes, holds promise that LSM, or their cellular products, could
      be used for immunotherapy of autoimmune diseases such as myasthenia gravis.

PMID- 10202111
TI  - Apoptotic human lymphocytes have diminished CD4 and CD8 receptor expression.
AB  - We used quantitative multiparameter flow cytometric assays to simultaneously
      detect viable, apoptotic, and necrotic human peripheral blood mononuclear cells
      (PBMC) and immunophenotyped lymphocyte subsets within the PBMC. Apoptosis was
      induced by a spectrum of treatments, including camptothecin, cisplatin,
      dexamethasone, hyperthermia, staurosporine, and etoposide in anti-CD3 mAb
      stimulated cells and by cyclohexamide in both quiescent and stimulated cells;
      apoptosis in the latter was augmented by anti-fas mAb. We found that CD4(+) and
      CD8(+) cells were significantly underrepresented in the apoptotic PBMC and that
      the percentage of CD4(+) and CD8(+) PBMC each markedly decreased as apoptosis
      increased. This suggested that surface expression of these receptors was lessened
      on apoptotic CD4(+) and CD8(+) cells. This was directly confirmed by observation
      of sorted CD4(+) PBMC. This analysis of a wide variety of apoptotic stimuli
      demonstrates that diminished CD4 and CD8 surface receptor expression is a common
      feature of human T lymphocyte apoptosis.

PMID- 10202112
TI  - Dendritic cell secretion of IL-15 is induced by recombinant huCD40LT and augments
      the stimulation of antigen-specific cytolytic T cells.
AB  - Dendritic cells (DC) are professional antigen-presenting cells which stimulate
      strong proliferative and cytolytic T cell responses. Stimulation of CD40 on
      dendritic cells by its ligands and anti-CD40 antibodies induces maturation and
      enhances DC stimulatory ability. In order to understand the mechanism by which
      ligand:CD40 interactions augment DC function, we assessed the role of T cell
      stimulatory cytokines IL-12 and IL-15 in the function of DC stimulated with
      soluble trimeric CD40L, a recombinant fusion protein incorporating three
      covalently linked extracellular CD40L domains (huCD40LT). Peripheral blood
      derived DC treated with huCD40LT and/or IFN-gamma were used to stimulate T cell
      responses in vitro to specific antigens. DC treated with huCD40LT or IFN
      gamma/huCD40LT stimulated enhanced T cell proliferation to CASTA, a soluble
      protein from C. albicans, induced T cells with augmented antigen-specific lysis,
      and increased the yield of antigen-specific IFN-gamma-producing T cells. IL-15
      production by DC was enhanced in cultures treated with huCD40LT and correlated
      with expansion of antigen-specific cytolytic T cells. Addition of a neutralizing
      anti-IL-15 monoclonal antibody inhibited the expansion of viral and tumor antigen
      specific T cells stimulated by IFN-gamma and huCD40LT-treated DC. In contrast,
      this enhanced stimulatory ability of DC did not appear to depend on synthesis of
      IL-12 since huCD40LT treatment stimulated the generation of antigen-specific
      cytokine producing and cytolytic T cells without increased IL-12 production.
      Addition of anti-IL-12 monoclonal antibody did not inhibit expansion of these
      cells. These data suggest that production of IL-15 but not IL-12 is an important
      factor in the enhanced immunostimulatory ability of huCD40LT-treated DC.

PMID- 10202113
TI  - Rapid anti-helminthic response of B lymphocytes in the intestinal mucosal tissues
      of rats.
AB  - B cell response to Trichinella spiralis (Ts) adult antigen (Ag) was studied in
      rats 1-20 days postinfection. B cell recoveries from the mesenteric lymph node
      (MLN), Peyer's patches (PP), thoracic duct lymph (TDL), and the spleen were
      determined by FACS analysis and Ag-specific antibody-producing cells (Ab-pc) in
      these tissues were enumerated using the immunoplaque assay. Total B cell numbers
      increased 2-70 times from day 3 postinfection in the MLN and TDL obtained from
      MLN-resected rats (MX) and such proliferation was not found in the PP or the
      spleen. Ab-pc of all isotypes increased from day 3 in the MLN and from day 2 in
      the MX-TDL. Among all isotypes, IgE- and IgG1-pc showed the strongest response.
      Immunofluorescence study revealed that these B cells were activated in the non-PP
      region of the small intestine. These results indicate an early isotype switch to
      IgG1 and IgE production in Ts-infected small intestine.

PMID- 10202114
TI  - Requirement of I-E molecule for thymocyte apoptosis induced by staphylococcal
      enterotoxin B in vivo.
AB  - In vivo administration of bacterial superantigen staphylococcal enterotoxin B
      (SEB) to BALB/c mice led to thymus atrophy resulting from thymocyte apoptosis. In
      this study, we demonstrated that SEB induced a substantial reduction in thymocyte
      numbers in BALB/c, B10. D2 (H-2(d) haplotype), B10.BR, C3H/HeJ, C3H/HeN (H-2(k)),
      and (BALB/c x B6)F1 (H-2(dxb)), but caused little or no effect in I-E- strains
      such as B6, B10, A.BY (H-2(b)), and A.SW (H-2(s)) mice. Elimination of
      CD4(+)CD8(+) cells predominantly accounted for the thymocyte loss, although the
      numbers of other subpopulations may also be reduced. Thymocyte apoptosis was
      shown by an increase in the level of DNA fragmentation in BALB/c but not in B6
      mice after SEB administration. Treatment with anti-I-Ed monoclonal antibody to
      BALB/c mice blocked SEB-induced thymocyte apoptosis when anti-I-Ad exerted less
      effect. In contrast to SEB, staphylococcal enterotoxin A led to comparable levels
      of thymus atrophy in BALB/c and B6 mice. Studies on the surface marker expression
      indicated that CD25 expression was upregulated on BALB/c mouse thymocytes but
      with only a moderate increase in B6 mice. The CD4(+)CD8(+) cells were the major
      (>90%) population that expressed elevated levels of CD25 in BALB/c mice. An
      increase in the expression of TCRalphabeta, CD3, and CD69 surface markers was
      also observed on thymocytes from BALB/c mice, but not from I-E- strains. The
      differential response of I-E+ and I-E- mice to SEB may be exploited as a model
      for the study of apoptosis in the thymus.

PMID- 10202115
TI  - Apoptosis induced by crosslinking of CD4 on activated human B cells.
AB  - Using immunofluorescence, RT-PCR, and Western blotting, we have demonstrated the
      ability of human B cells to express CD4. In each of the 10 lymphoblastoid cell
      lines (LCL) tested there was variable, but definite, proportion of CD4-positive B
      cells. Expression of CD4 was related to the cell cycle; CD4 was expressed in the
      G1 phase and continued at later phases of the cell cycle. CD4 was in part
      internalized and degraded by the LCL B cells. Surface CD4 was associated to lck
      and its crosslinking resulted in tyrosine phosphorylation. Additional experiments
      conducted on freshly prepared tonsillar B cells demonstrated that CD4 was
      expressed by large activated B cells, but not by small resting B cells. However,
      not all the activated tonsillar B cells had surface CD4 since germinal center
      cells were CD4-negative. Crosslinking of CD4 on LCL or on tonsillar activated B
      cells resulted in apoptosis in vitro, a finding that indicates the capacity of
      CD4 to deliver functional signals to B cells and to play a regulatory function in
      their physiology. Exposure of CD4 expressing B cells to gp120 under conditions
      that resulted in CD4 crosslinking also caused apoptosis suggesting some
      implications for the pathophysiology of AIDS.

PMID- 10202116
TI  - Prostaglandins mediate suppression of lymphocyte proliferation and cytokine
      synthesis in acute Trypanosoma cruzi infection.
AB  - Suppression of host lymphoproliferative responses to mitogens and Ag is
      characteristically seen during acute infection with the protozoan parasite
      Trypanosoma cruzi. We investigated the reciprocal regulation of prostaglandins
      (PG), TNF-alpha, and nitric oxide (NO) production and their effects on cytokine
      production and lymphoproliferative responses to parasite Ag and to Con A by
      spleen cells (SC) from T.-cruzi-infected mice. Large amounts of PGE2, TNF-alpha,
      and NO were produced during infection. TNF-alpha stimulated PG and NO synthesis,
      while both mediators inhibited TNF-alpha synthesis. Blocking PG also reduced NO
      synthesis indicating that PG stimulate NO production. Treatment with indomethacin
      or NMLA stimulated lymphoproliferation on days 6 and 22 of infection; on day 14,
      when suppression of proliferation and NO production was maximal, combined
      inhibition of NO and PG production restored parasite Ag specific and Con A
      proliferative responses. Blocking PG or NO production increased IL-2, IFN-gamma,
      and TNF-alpha, but not IL-12 production by SC; IL-10 levels were not reduced.
      Indomethacin-treated infected mice had higher mortality compared to untreated
      infected animals. The data indicate that PG, together with NO and TNF-alpha,
      participate in a complex circuit that controls lymphoproliferative and cytokine
      responses in T. cruzi infection.

PMID- 10202117
TI  - Cross-reactivity of T-cell clones specific for altered peptide ligands of myelin
      basic protein.
AB  - We have determined that certain altered peptide ligands (APLs) can induce T-cells
      specific for the native peptide myelin basic protein (MBP) p85-99 to secrete Th2
      type cytokines such as IL-4 and IL-5 in the absence of significant Th1-type
      cytokines. However, it is not known whether stimulation with APLs will activate
      autoreactive T cells or a distinct population of cells. In the present study, 18
      T-cell clones that reacted with either MBP p85-99 or one of three APLs of the
      peptide substituted at TCR contact residues were generated. T-cells were tested
      functionally for their reactivity to the original stimulating peptide as well as
      to the MBP APLs. In addition, the T-cell receptor (TCR) alpha and beta chains of
      each of these clones were sequenced. In a series of T-cell clones isolated from a
      multiple sclerosis patient, stimulation of T-cells with the APL 93A, which has an
      alanine for lysine substitution at the TCR contact residue 93, did not induce
      substantial proliferation of MBPp85-99-specific T-cell clones, indicating that a
      distinct set of T-cell clones was induced. However, this was not the case for
      another set of T-cell clones from a different individual in which the 93A peptide
      induced clonal expansion of T-cells highly reactive with the native MBPp85-99
      antigen. Thus, the potential beneficial effect of using APLs to induce
      downregulatory cytokines appears to depend on the specific T-cell repertoire of
      the individual patient.

PMID- 10202118
TI  - MHC class I molecules on CD4 T cells regulate receptor-mediated activation
      signals.
AB  - Three T cell populations can be distinguished based on their response to antigen
      receptor engagement. A sizable fraction dies within hours of TCR ligation, a
      smaller fraction enters the mitotic cycle, and the remaining T cells merely
      upregulate the expression of certain cell surface markers. An MHC-I-controlled
      regulatory mechanism has been identified. MHC I MAbs, or Fab fragments, prevent T
      cells from mounting a proliferative mitogen response but do not inhibit the
      mitogen-induced deletion of T cells. IFN-gamma enlarges the fraction of T cells
      which proliferate in response to mitogen stimulation but, in the presence of MHC
      I MAb, these cells fail to clonally expand and enter the deletion pathway.
      Phenotypically, MHC I MAb Fab fragments induce T cells to upregulate the
      expression of the apoptosis marker CD95, even in the absence of TCR ligand, and
      prevent the upregulation of costimulatory CD28 molecule expression.

PMID- 10202119
TI  - Energetic and endocrine mediation of natal dispersal behavior in Belding's ground
      squirrels.
AB  - Natal dispersal, the permanent departure of an individual from its birth site, is
      sex biased in most mammals, with males dispersing at higher rates or over greater
      distances than do female conspecifics. Because dispersal movements may be
      energetically expensive, their occurrence should theoretically be influenced by
      energy availability. Moreover, the male bias typical of mammalian dispersal
      suggests that this behavior might be mediated by gonadal androgens. Using free
      living Belding's ground squirrels (Spermophilus beldingi) as subjects, we
      provisioned juveniles with extra food to evaluate energetic influences on male
      dispersal behavior. Provisioning increased body mass and body fat of juvenile
      males and caused them to disperse at younger ages, but did not affect blood
      glucose levels. Dispersing males were fatter than same-aged males that had not
      yet dispersed. Moreover, body fat of provisioned and unprovisioned males did not
      differ when evaluated relative to the week during which they dispersed,
      suggesting that there may be a fat threshold for dispersal. In a second
      experiment, we measured plasma concentrations of testosterone (T) in provisioned
      and unprovisioned, free-living juveniles to evaluate the hypothesis that male
      dispersal behavior is activated by concurrent high levels of T. We observed no
      increase in plasma T associated with dispersal by juvenile males, no sex
      differences in circulating T among juveniles, and no effects of food provisioning
      on juvenile T levels. In a third experiment with free-living S. beldingi, we
      concurrently altered early androgen exposure by treating females with T at birth
      and manipulated energy availability by food provisioning. Perinatal T-treatment
      increased the likelihood of dispersal among juvenile females. Provisioning
      increased body mass and body fat of juveniles and caused males and T-treated
      females to disperse at significantly younger ages than either their unprovisioned
      counterparts or the few provisioned control females that dispersed. These results
      suggest that early T exposure in this species determines the probability of
      dispersal, whereas the amount of energy an individual has stored as fat strongly
      influences the timing of dispersal. Early T exposure also appears to cause the
      timing of dispersal to respond to energy availability and body fat in a male
      typical way, possibly by organizing masculine mass and fat thresholds for
      dispersal.

PMID- 10202120
TI  - Seasonal and social correlates of fecal testosterone and cortisol levels in wild
      male muriquis (Brachyteles arachnoides).
AB  - Fecal testosterone and cortisol levels were analyzed from six wild male muriquis
      (Brachyteles arachnoides) over a 19-month period at the Estacao Biologica de
      Caratinga in Minas Gerais, Brazil, to investigate the hormonal correlates of
      seasonal sexual behavior and environmental conditions. Group mean testosterone
      levels based on weekly samples from the six males did not differ between
      copulatory and noncopulatory periods or between rainy and dry seasons. Cortisol
      levels did change with copulatory periods, and were significantly higher during
      the second dry season, when mating continued following an exceptionally heavy
      rainy season, than during the first dry season, when mating ceased. Males
      exhibited individual variation in the timing of their hormone shifts relative to
      their sexual activity, but neither hormone levels nor sexual activity were
      related to male age. Despite individual differences in the timing of testosterone
      fluctuations around the onset and offset of the copulatory season, all males
      exhibited elevated cortisol concentrations following a slight increase in
      testosterone at the beginning of the copulatory season. Both the lack of
      significant changes in testosterone levels with the onset of the rainy and
      copulatory season and the lack of prebreeding increases in cortisol may be
      related to the low levels of overt aggression displayed by male muriquis over
      access to mates.

PMID- 10202121
TI  - Parental and first generation effects of exogenous 17beta-estradiol on
      reproductive performance of female zebra finches (Taeniopygia guttata).
AB  - Steroids hormones have numerous "activational" effects in adult birds, regulating
      sexual behavior, and more recently maternal androgens have been shown to have
      potentially important "organizational" effects in ovo, influencing offspring
      growth, development, and behavior. In this study I investigated parental and
      first-generation effects of exogenous estrogens on female reproduction in zebra
      finches (Taeniopygia guttata). 17beta-Estradiol (E2; 1.2 microg/g, 4 daily
      injections i.m.) elevated plasma levels of the yolk precursors, vitellogenin
      (VTG) and very low-density lipoprotein (VLDL), in nonbreeding females to levels
      similar to those of breeding females. However, E2-treatment of breeding females
      caused no significant change in plasma VTG or VLDL levels compared to control
      birds (measured at the 1-egg stage), and there was no difference in reproductive
      performance between groups (egg size, clutch size, timing of laying). E2-treated
      females produced significantly more daughters than sons (21F:8M) at fledging,
      compared to control females (18F:19M). Nestling mortality was significantly
      higher in broods of E2-treated females, suggesting that the skewed sex ratio may
      have resulted from differential mortality of male chicks. The pattern of chick
      mortality in E2-broods was not consistent with this being caused by estrogen
      mediated changes in parental behavior (e.g., provisoning). Mean egg mass of
      daughters of E2-treated females was typical of experienced, adult breeders, and
      larger than normal, first-time breeders or control offspring (0.947 vs 0.850 g).
      There was no treatment effect on offspring clutch size or laying interval. These
      results suggest that early exposure to maternal estrogens in ovo might be
      involved in establishing intraindividual variation in female-specific phenotypic
      traits, as has previously been demonstrated for androgens and male behavioral
      traits (e.g., aggression).

PMID- 10202122
TI  - Paced mating behavior in female rats in response to different hormone priming
      regimens.
AB  - A female rat will display a repertoire of behaviors during a sexual encounter
      with a male rat including sexually receptive (the lordosis response) and
      proceptive (hopping, darting) behaviors. In addition, when given the opportunity,
      a sexually receptive female rat will approach and withdraw from the male rat,
      controlling the timing of the receipt of mounts, intromissions, and ejaculations,
      a behavior known as paced mating behavior. The present experiments tested the
      hypotheses (1) that progesterone regulates paced mating behavior, and (2) that
      multiple hormone regimens used previously to induce sexual receptivity have the
      same effect on paced mating behavior. Paced mating behavior was assessed in
      sexually receptive ovariectomized female rats after treatment with: (1) estradiol
      benzoate (EB; 30.0 mg/kg) followed by a range of doses of progesterone (P; 1.0
      8.0 mg/kg), (2) two pulses of unesterified estradiol (E2; 2.0 microg/rat)
      followed by 1.0 mg/rat of P, and (3) EB alone (5.0 microg/rat) for 6 days. No
      differences in sexual receptivity or in paced mating behavior were observed
      across doses of P (1.0-8.0 mg/kg). In contrast, the number of hops and darts per
      min increased with the dose of P administered. E2 + P administration resulted in
      slightly, but significantly, lower levels of sexual receptivity along with
      significantly longer contact-return latencies following an intromission in
      relation to the other treatment conditions. In addition, female rats exhibited
      fewer hops and darts per min in response to E2 + P than in response to EB + 8.0
      mg/kg of P. The administration of EB alone for 6 days induced levels of
      receptivity and paced mating behavior indistinguishable from EB + P, while
      eliciting significantly fewer hops and darts per min than the EB + 8.0 mg/kg P
      treatment condition. Hormone priming regimen had no effect on the percentage of
      exits displayed during the paced mating tests in any experimental phase. Dose of
      P had no effect on paced mating behavior in sexually receptive rats. In addition,
      P does not appear to be necessary for the display of paced mating behavior
      following long-term treatment with EB. In contrast, the pulsatile administration
      of E2 + P induced a different pattern of paced mating behavior in sexually
      receptive rats.

PMID- 10202123
TI  - Brain androgen-inducible aromatase is critical for adolescent organization of
      environment-specific social interaction in male rats.
AB  - Previous observations have indicated that specific behavioral responses to
      anxiogenic stimuli emerge over adolescent development in male rats and that
      gonadal androgens during puberty are essential for this emergence. The objective
      of the current study was to evaluate mechanisms via which androgens might be
      organizing the brain during adolescence for appropriate mature adaptive
      responses. Male rats were exposed to fadrozole (an aromatase inhibitor, 5 mg/kg),
      flutamide (an androgen receptor antagonist, 10 mg/kg), or MK-434 (a 5 alpha
      reductase inhibitor, 10 mg/kg) from day 29 to 60 and tested for environment
      specific social interaction (SI) at 60 days of age. The emergence of adult
      typical SI was impaired by exposure to the aromatase inhibitor and to the
      antiandrogen, whereas exposure to the 5 alpha-reductase inhibitor was without
      effect. Peripheral indices of drug effects indicated that the respective
      mechanisms had been altered by the different compounds. These results suggest
      that testosterone induction of aromatase is critical for the organization of
      mature SI behavior in male rats over adolescent development.

PMID- 10202124
TI  - Hormonal changes in males of a naturally biparental and a uniparental mammal.
AB  - Blood samples from male hamsters (Phodopus) during their mate's gestation and
      early lactation show that key hormones important in maternal behavior are also
      changing in males and differ for two closely related species with different
      levels of paternal care. Results of study 1 were consistent with a relationship
      between higher prolactin, lower testosterone and paternal behavior during early
      lactation in P. campbelli and provided no evidence for similar hormonal changes
      in P. sungorus. Study 2 sampled males before or after the birth. Prolactin did
      not increase until at least one day after the birth in P. campbelli but was high
      at the end of the pregnancy in P. sungorus. Increasing testosterone
      concentrations in P. campbelli as the birth approached were consistent with mate
      guarding, high testosterone concentrations on L5 were consistent with paternal
      aggression in defense of the litter, and the drop in testosterone after the birth
      was consistent with reduced aggression toward the new pups. Results confirmed
      that cortisol concentrations were reduced following the establishment of a pair
      bond and found that P. campbelli males had elevated cortisol before the birth.
      Results support the hypothesis that mammalian paternal behavior has a hormonal
      basis which is analogous to maternal behavior.

PMID- 10202125
TI  - Protein synthesis in the medial preoptic area is important for the mating-induced
      decrease in estrus duration in hamsters.
AB  - Sexual receptivity in female hamsters potentially lasts for about 16 h. However,
      vaginal cervical stimulation (VCS) from a male during mating eventually reduces
      receptivity and can shorten the duration of behavioral estrus. The process by
      which this change in response to the male takes place is unknown. Recently,
      detection of the Fos protein has indicated that the medial preoptic area (POA) is
      one of the brain regions particularly responsive to VCS. Additionally, the POA
      may have an inhibitory effect on sexual receptivity. To determine if protein
      synthesis in the POA is required to initiate the VCS-induced decrease in estrus
      duration, a protein synthesis inhibitor (anisomycin, 0.50 microg) or a control
      substance (cholesterol) was applied bilaterally to the POA of steroid-primed
      ovariectomized female hamsters. Females were tested with a sexually active male
      at five time points following the initial test for sexual receptivity (hour 1, 2,
      6, 12, and 24). Half of the females tested were allowed to receive VCS from a
      male, while half were fitted with vaginal masks to prevent penile intromission.
      Each group receiving VCS showed a significant decrease in lordosis duration
      evident between hour 2 and hour 6, except the group which received anisomycin in
      the POA. In this respect the POA anisomycin group was similar to animals which
      did not receive VCS. Hamsters with vaginal masks and the anisomycin/POA animals
      allowed to receive VCS exhibited their first decrease in lordosis duration
      between hour 6 and hour 12. These results indicate that protein synthesis is
      important for VCS-induced decrease in estrus duration in the POA.

PMID- 10202126
TI  - Investigation of the role of postnatal testosterone in the expression of sex
      differences in behavior in infant rhesus macaques (Macaca mulatta).
AB  - In several primate species, males have been shown to exhibit a surge in
      circulating testosterone during the early postnatal period. This surge has been
      postulated to play a role in the development of sex differences in behavior. In
      this study, the role of postnatal testosterone in infant behavioral development
      was investigated in socially living rhesus macaques. Seven male infants were
      treated with a GnRH agonist, avorelin, from the first week of life onwards. Ten
      female infants were exposed to testosterone by implantation of capsules
      containing testosterone. The behavioral development of these and control infants
      was recorded from birth to 6 months of age. The sexually dimorphic patterns of
      play and mounting were not affected by manipulation of postnatal testosterone in
      either male or female infants. Similarly, most mother-infant interactions were
      not affected by the hormonal manipulation of infants. Mothers of testosterone
      treated females were found to take more responsibility for moving into and out of
      arm's reach of their infants than mothers of some other groups of infants;
      however, this measure did not normally differ between mothers of male and female
      infants. Manipulation of the postnatal testosterone surge does significantly
      affect penile growth and development, but does not affect the expression of
      infant sex differences in behavior nor greatly affect the development of the
      mother-infant relationship in rhesus macaques.

PMID- 10202127
TI  - Self-injurious behavior is decreased by cyproterone acetate in adult male rhesus
      (Macaca mulatta).
AB  - Self-injurious behavior (SIB) presents a serious problem in laboratory macaques
      that cannot be socially housed for scientific reasons and among institutionalized
      children and adults where it is often associated with different forms of brain
      dysfunction. We have experienced limited success in reducing SIB in macaques by
      enhancing their environment with enrichment devices. Psychotropic drugs also
      help, but problems are associated with their use. Because sexual and aggressive
      behavioral problems in men have been treated with progestational drugs, we tested
      the efficacy of cyproterone acetate (CA, 5-10 mg/kg/week) on reducing SIB in 8
      singly housed, adult male rhesus macaques. The main findings were: (1) SIB and
      other atypical behaviors were significantly reduced during CA treatment; (2)
      serum testosterone was significantly reduced during CA treatment; (3) cerebral
      spinal fluid (CSF) levels of 5HIAA and HVA, metabolites of serotonin and
      dopamine, respectively, declined significantly during CA treatment; (4) the
      duration of SIB positively correlated with levels of 5HIAA in CSF; but (5) sperm
      counts were not reduced during treatment. Thus, CA was a partially effective
      treatment (3 months) for adult male macaques whose behavioral problems include
      SIB. In summary, CA reduced SIB, overall aggression, serum testosterone, CSF
      5HIAA, and CSF HVA. We hypothesized that the progestin activity of CA represses
      the hypothalamic gonadal axis and decreases testosterone, which in turn decreases
      SIB. In addition, we speculate that the decrease in 5HIAA and HVA in CSF may have
      been caused by progestins decreasing the activity of MAO. Therefore, the
      reduction of SIB may also be related to an increase in the availability of active
      monoamines in the CNS.

PMID- 10202128
TI  - Tumor markers. Introduction.

PMID- 10202129
TI  - The carcinoembryonic antigen (CEA) family: structures, suggested functions and
      expression in normal and malignant tissues.
AB  - The human CEA family has been fully characterized. It comprises 29 genes of which
      18 are expressed; 7 belonging to the CEA subgroup and 11 to the pregnancy
      specific glycoprotein subgroup. CEA is an important tumor marker for colorectal
      and some other carcinomas. The CEA subgroup members are cell membrane associated
      and show a complex expression pattern in normal and cancerous tissues with
      notably CEA showing a selective epithelial expression. Several CEA subgroup
      members possess cell adhesion properties and the primordial member, biliary
      glycoprotein, seems to function in signal transduction or regulation of signal
      transduction possibly in association with other CEA sub-family members. A
      modified ITAM/ITIM motif is identified in the cytoplasmatic domain of BGP. A role
      of CEA in innate immunity is envisioned.

PMID- 10202130
TI  - Prostate-specific antigen.
AB  - Prostate specific antigen (PSA) is serine protease produced at high
      concentrations by normal and malignant prostatic epithelium. It is mainly
      secreted into seminal fluid, where it digests the gel forming after ejaculation.
      Only minor amounts of PSA leak out into circulation from the normal prostate, but
      the release of PSA is increased in prostatic disease. Thus PSA is a sensitive
      serum marker for prostate cancer but its specificity is limited by a high
      frequency of falsely elevated values in men with benign prostatic hyperplasia
      (BPH). Approximately two-thirds of all elevated values (>4 microg/l) in men over
      50 years of age are due to BPH. In serum, most of the PSA immunoreactivity
      consists of a complex between PSA and alpha1-antichymotrypsin (PSA-ACT) whereas
      approximately 5-40% are free. The proportion of PSA-ACT is larger and the free
      fraction is smaller in prostate cancer than in benign prostatic hyperplasia
      (BPH). Determination of the proportion of free PSA has become widely used to
      improve the cancer specificity of PSA especially in men with PSA values in the
      'grey zone' (4-10 microg/l). PSA also occurs in complexes with other protease
      inhibitors and determination of these and other markers may further improve the
      diagnostic accuracy for prostate cancer. Interpretation of the results for many
      different markers is complicated, but this can be simplified by using statistical
      methods. The diagnostic accuracy can be further improved by using logistic
      regression or neural networks to estimate the combined impact of marker results
      and other findings like digital rectal examination (DRE), transrectal ultrasound
      (TRUS) and heredity.

PMID- 10202131
TI  - Cellular aspects of alpha-fetoprotein reexpression in tumors.
AB  - The cellular basis of AFP synthesis in normal development, liver regeneration,
      hepatocarcinogenesis and in tumors is discussed in the review. The attempt is
      made to interpret the production of AFP by germ cell and liver tumors as a
      consequence of their origin from the cell types producing AFP in normal
      conditions. Thus, AFP in germ cell tumors is explained by the development of the
      yolk sac visceral endoderm (YSVE) in teratocarcinomas, since YSVE is the first
      site of AFP synthesis in the embryo. The next site of AFP production is embryonal
      hepatoblast and just hepatoblastomas are the maximal producers of AFP among liver
      cancers. The reason for AFP resumption in hepatocellular carcinomas (HCC) is not
      yet clear. This problem is discussed in the light of possible role of oval cells
      in the HCC origin and the concept of the two states of the mature hepatocyte,
      associated and non-associated with AFP production. The crucial role of
      extracellular matrix in the control of AFP-producing state of hepatocyte is
      emphasized.

PMID- 10202133
TI  - CA 125: fundamental and clinical aspects.
AB  - Since the OC 125 monoclonal antibody (Mab) was generated, other Mabs to the CA
      125 glycoprotein have been produced and classified into two families associated
      with two major epitope regions on the CA 125 molecule. New generation assays,
      combining Mabs to two distinct regions of the molecule, compare favorably with
      that of the original assays as demonstrated by ROC curves. The original CA 125
      assay suffered from interference of HAMA, an important drawback considering the
      increasing use of murine antibodies for immunodiagnosis and treatment of ovarian
      cancer. This problem has been solved for the majority of currently available
      tests. The sensitivity of the assays for early ovarian cancer remains low,
      precluding its indiscriminate use for screening and diagnosis of ovarian cancer.
      Its use in screening for early cancer, combined with ultrasonography, is limited
      to high risk populations, such as women from families with mutations in the BRCA1
      or 2 gene. Although CA 125 assessment may play a limited role in the (early)
      detection of ovarian cancer, its role in the follow-up during and after therapy
      is well established. The major contribution of CA 125 is in the monitoring of
      tumor response to chemotherapy, where it is valuable in detecting those patients
      with an inadequate response to the chosen treatment. The role of CA 125 in early
      detection of recurrences remains to be established and is currently the subject
      of two large clinical trials.

PMID- 10202132
TI  - Alpha-fetoprotein gene regulation: lessons from transgenic mice.
AB  - The mouse alpha-fetoprotein (AFP) gene provides an excellent model system to
      study developmental gene activation and different aspects of liver-specific
      transcriptional control. AFP is activated early in hepatogenesis, repressed post
      natally, and can be reactivated during liver regeneration and in hepatocellular
      carcinomas. Transgenic studies have also revealed that AFP enhancers, when linked
      individually to a heterologous promoter, can confer zonal control in the adult
      liver. Continued transgenic studies, combined with analysis using in vitro and
      tissue culture systems, will help elucidate mechanisms of transcriptional
      regulation during liver development and hepatocarcinogenesis.

PMID- 10202134
TI  - The HER-2/neu oncogene: prognostic factor, predictive factor and target for
      therapy.
AB  - The HER-2/neu oncogene encodes a transmembrane tyrosine kinase receptor with
      extensive homology to the epidermal growth factor receptor. HER-2/neu has been
      widely studied in breast cancer. The potential value of HER-2/neu status for the
      prediction of disease outcome and response to therapy in breast cancer is
      presented in the light of a series of recently published studies showing a range
      of impact on the outcome of patients treated with hormonal, cytotoxic and
      radiation therapies. This review includes the application of serum-based HER
      2/neu testing and the use of antibody-based therapies directed against the HER
      2/neu protein and their potential to become a new modality for breast cancer
      treatment.

PMID- 10202135
TI  - Molecular markers of B-cell lymphoma.
AB  - Molecular mapping of the cell surface has probably proceeded further with the
      human lymphocyte than with any other mammalian cell, and the B lymphocyte yields
      a wide range of subtly varying neoplasms. These two bodies of knowledge are now
      readily correlated, given the widespread adoption of a modern lineage-based
      classification of lymphoma (Revised European-American). Studies of the markers of
      B-cell lymphoma have immediate practical importance in diagnosis, defining
      clonality, and detecting minimal residual disease. They also help to keep us
      abreast of lymphocyte physiology, and present new opportunities for treating
      these neoplasms.

PMID- 10202136
TI  - Molecular tinkering of G protein-coupled receptors: an evolutionary success.
AB  - Among membrane-bound receptors, the G protein-coupled receptors (GPCRs) are
      certainly the most diverse. They have been very successful during evolution,
      being capable of transducing messages as different as photons, organic odorants,
      nucleotides, nucleosides, peptides, lipids and proteins. Indirect studies, as
      well as two-dimensional crystallization of rhodopsin, have led to a useful model
      of a common 'central core', composed of seven transmembrane helical domains, and
      its structural modifications during activation. There are at least six families
      of GPCRs showing no sequence similarity. They use an amazing number of different
      domains both to bind their ligands and to activate G proteins. The fine-tuning of
      their coupling to G proteins is regulated by splicing, RNA editing and
      phosphorylation. Some GPCRs have been found to form either homo- or heterodimers
      with a structurally different GPCR, but also with membrane-bound proteins having
      one transmembrane domain such as nina-A, odr-4 or RAMP, the latter being involved
      in their targeting, function and pharmacology. Finally, some GPCRs are unfaithful
      to G proteins and interact directly, via their C-terminal domain, with proteins
      containing PDZ and Enabled/VASP homology (EVH)-like domains.

PMID- 10202137
TI  - Protection of Escherichia coli cells against extreme turgor by activation of MscS
      and MscL mechanosensitive channels: identification of genes required for MscS
      activity.
AB  - Mechanosensitive channels are ubiquitous amongst bacterial cells and have been
      proposed to have major roles in the adaptation to osmotic stress, in particular
      in the management of transitions from high to low osmolarity environments.
      Electrophysiological measurements have identified multiple channels in
      Escherichia coli cells. One gene, mscL, encoding a large conductance channel has
      previously been described, but null mutants were without well-defined phenotypes.
      Here, we report the characterization of a new gene family required for MscS
      function, YggB and KefA, which has enabled a rigorous test of the role of the
      channels. The channel determined by KefA does not appear to have a major role in
      managing the transition from high to low osmolarity. In contrast, analysis of
      mutants of E.coli lacking YggB and MscL shows that mechanosensitive channels are
      designed to open at a pressure change just below that which would cause cell
      disruption leading to death.

PMID- 10202138
TI  - A new crystal structure, Ca2+ dependence and mutational analysis reveal molecular
      details of E-cadherin homoassociation.
AB  - Electron microscopy of ECADCOMP, a recombinant E-cadherin ectodomain pentamerized
      by the assembly domain of cartilage oligomeric matrix protein, has been used to
      analyze the role of cis-dimerization and trans-interaction in the homophilic
      association of this cell adhesion molecule. The Ca2+ dependency of both
      interactions was investigated. Low Ca2+ concentrations (50 microM) stabilized the
      rod-like structure of E-cadherin. At medium Ca2+ concentration (500 microM), two
      adjacent ectodomains in a pentamer formed cis-dimers. At high Ca2+ concentration
      (>1 mM), two cis-dimers from different pentamers formed a trans-interaction. The
      X-ray structure of an N-terminal domain pair of E-cadherin revealed two molecules
      per asymmetric unit in an intertwisted X-shaped arrangement with closest contacts
      in the Ca2+-binding region between domains 1 and 2. Contrary to previous data,
      Trp2 was docked in the hydrophobic cavity of its own molecule, and was therefore
      not involved in cis-dimerization of two molecules. This was supported further by
      W2A and A80I (a residue involved in the hydrophobic cavity surrounding Trp2)
      mutations in ECADCOMP which both led to abrogation of the trans- but not the cis
      interaction. Structural and biochemical data suggest a link between Ca2+ binding
      in the millimolar range and Trp2 docking, both events being essential for the
      trans-association.

PMID- 10202139
TI  - Tyrosine phosphorylation of p62(Dok) induced by cell adhesion and insulin:
      possible role in cell migration.
AB  - Dok, a 62-kDa Ras GTPase-activating protein (rasGAP)-associated phosphotyrosyl
      protein, is thought to act as a multiple docking protein downstream of receptor
      or non-receptor tyrosine kinases. Cell adhesion to extracellular matrix proteins
      induced marked tyrosine phosphorylation of Dok. This adhesion-dependent
      phosphorylation of Dok was mediated, at least in part, by Src family tyrosine
      kinases. The maximal insulin-induced tyrosine phosphorylation of Dok required a
      Src family kinase. A mutant Dok (DokDeltaPH) that lacked its pleckstrin homology
      domain failed to undergo tyrosine phosphorylation in response to cell adhesion or
      insulin. Furthermore, unlike the wild-type protein, DokDeltaPH did not localize
      to subcellular membrane components. Insulin promoted the association of tyrosine
      phosphorylated Dok with the adapter protein NCK and rasGAP. In contrast, a mutant
      Dok (DokY361F), in which Tyr361 was replaced by phenylalanine, failed to bind NCK
      but partially retained the ability to bind rasGAP in response to insulin.
      Overexpression of wild-type Dok, but not that of DokDeltaPH or DokY361F, enhanced
      the cell migratory response to insulin without affecting insulin activation of
      mitogen-activated protein kinase. These results identify Dok as a signal
      transducer that potentially links, through its interaction with NCK or rasGAP,
      cell adhesion and insulin receptors to the machinery that controls cell motility.

PMID- 10202140
TI  - Maturation of the axonal plasma membrane requires upregulation of sphingomyelin
      synthesis and formation of protein-lipid complexes.
AB  - Neuronal maturation is a gradual process; first axons and dendrites are
      established as distinct morphological entities; next the different intracellular
      organization of these processes occurs; and finally the specialized plasma
      membrane domains of these two compartments are formed. Only when this has been
      accomplished does proper neuronal function take place. In this work we present
      evidence that the correct distribution of a class of axonal membrane proteins
      requires a mechanism which involves formation of protein-lipid
      (sphingomyelin/cholesterol) detergent-insoluble complexes (DIGs). Using
      biochemistry and immunofluorescence microscopy we now show that in developing
      neurons the randomly distributed Thy-1 does not interact with lipids into DIGs
      (in fully developed neurons the formation of such complexes is essential for the
      correct axonal targeting of this protein). Using lipid mass spectrometry and thin
      layer chromatography we show that the DIG lipid missing in the developing neurons
      is sphingomyelin, but not cholesterol or glucosylceramide. Finally, by increasing
      the intracellular levels of sphingomyelin in the young neurons the formation of
      Thy-1/DIGs was induced and, consistent with a role in sorting, proper axonal
      distribution was facilitated. These results emphasize the role of sphingomyelin
      in axonal, and therefore, neuronal maturation.

PMID- 10202141
TI  - Characterization of GAPCenA, a GTPase activating protein for Rab6, part of which
      associates with the centrosome.
AB  - The Rab6 GTPase regulates intracellular transport at the level of the Golgi
      apparatus, probably in a retrograde direction. Here, we report the identification
      and characterization of a novel human Rab6-interacting protein named human
      GAPCenA (for 'GAP and centrosome-associated'). Primary sequence analysis
      indicates that GAPCenA displays similarities, within a central 200 amino acids
      domain, to both the yeast Rab GTPase activating proteins (GAPs) and to the
      spindle checkpoint proteins Saccharomyces cerevisiae Bub2p and
      Schizosaccharomyces pombe Cdc16p. We demonstrate that GAPCenA is indeed a GAP,
      specifically active in vitro on Rab6 and, to a lesser extent, on Rab4 and Rab2
      proteins. Immunofluorescence and cell fractionation experiments showed that
      GAPCenA is mainly cytosolic but that a minor pool is associated with the
      centrosome. Moreover, GAPCenA was found to form complexes with cytosolic gamma
      tubulin and to play a role in microtubule nucleation. Therefore, GAPCenA may be
      involved in the coordination of microtubule and Golgi dynamics during the cell
      cycle.

PMID- 10202142
TI  - CLK-1 controls respiration, behavior and aging in the nematode Caenorhabditis
      elegans.
AB  - Mutations in the clk-1 gene of the nematode Caenorhabditis elegans result in an
      average slowing of a variety of developmental and physiological processes,
      including the cell cycle, embryogenesis, post-embryonic growth, rhythmic
      behaviors and aging. In yeast, a CLK-1 homologue is absolutely required for
      ubiquinone biosynthesis and thus respiration. Here we show that CLK-1 is fully
      active when fused to green fluorescent protein and is found in the mitochondria
      of all somatic cells. The activity of mutant mitochondria, however, is only very
      slightly impaired, as measured in vivo by a dye-uptake assay, and in vitro by the
      activity of succinate cytochrome c reductase. Overexpression of CLK-1 activity in
      wild-type worms can increase mitochondrial activity, accelerate behavioral rates
      during aging and shorten life span, indicating that clk-1 regulates and controls
      these processes. These observations also provide strong genetic evidence that
      mitochondria are causally involved in aging. Furthermore, the reduced respiration
      of the long-lived clk-1 mutants suggests that longevity is promoted by the age
      dependent decrease in mitochondrial function that is observed in most species.

PMID- 10202143
TI  - Assembly of thick filaments and myofibrils occurs in the absence of the myosin
      head.
AB  - We investigated the importance of the myosin head in thick filament formation and
      myofibrillogenesis by generating transgenic Drosophila lines expressing either an
      embryonic or an adult isoform of the myosin rod in their indirect flight muscles.
      The headless myosin molecules retain the regulatory light-chain binding site, the
      alpha-helical rod and the C-terminal tailpiece. Both isoforms of headless myosin
      co-assemble with endogenous full-length myosin in wild-type muscle cells.
      However, rod polypeptides interfere with muscle function and cause a flightless
      phenotype. Electron microscopy demonstrates that this results from an antimorphic
      effect upon myofibril assembly. Thick filaments assemble when the myosin rod is
      expressed in mutant indirect flight muscles where no full-length myosin heavy
      chain is produced. These filaments show the characteristic hollow cross-section
      observed in wild type. The headless thick filaments can assemble with thin
      filaments into hexagonally packed arrays resembling normal myofibrils. However,
      thick filament length as well as sarcomere length and myofibril shape are
      abnormal. Therefore, thick filament assembly and many aspects of
      myofibrillogenesis are independent of the myosin head and these processes are
      regulated by the myosin rod and tailpiece. However, interaction of the myosin
      head with other myofibrillar components is necessary for defining filament length
      and myofibril dimensions.

PMID- 10202144
TI  - Critical role for Ser20 of human p53 in the negative regulation of p53 by Mdm2.
AB  - In response to environmental stress, the p53 phosphoprotein is stabilized and
      activated to inhibit cell growth. p53 stability and activity are negatively
      regulated by the murine double minute (Mdm2) oncoprotein in an autoregulatory
      feedback loop. The inhibitory effect of Mdm2 on p53 has to be tightly regulated
      for proper p53 activity. Phosphorylation is an important level of p53 regulation.
      In response to DNA damage, p53 is phosphorylated at several N-terminal serines.
      In this study we examined the role of Ser20, a potential phosphorylation site in
      human p53, in the regulation of p53 stability and function. Substitution of Ser20
      by Ala (p53-Ala20) significantly increases the susceptibility of human p53 to
      negative regulation by Mdm2 in vivo, as measured by apoptosis and transcription
      activation assays. Mutation of Ser20 to Ala renders p53 less stable and more
      prone to Mdm2-mediated degradation. While the in vitro binding of p53 to Mdm2 is
      not increased by the Ala20 mutation, the same mutation results in a markedly
      enhanced binding in vivo. This is consistent with the conclusion that
      phosphorylation of Ser20 in vivo attenuates the binding of wild-type p53 to Mdm2.
      Peptides bearing non-phosphorylated Ser20 or Ala20 compete with p53 for Mdm2
      binding, while a similar peptide with phosphorylated Ser20 does not. This implies
      a critical role for Ser20 in modulating the negative regulation of p53 by Mdm2,
      probably through phosphorylation-dependent inhibition of p53-Mdm2 interaction.

PMID- 10202145
TI  - DNA damage-inducible phosphorylation of p53 at N-terminal sites including a novel
      site, Ser20, requires tetramerization.
AB  - Upon DNA damage, p53 has been shown to be modified at a number of N-terminal
      phosphorylation sites including Ser15 and -33. Here we show that phosphorylation
      is induced as well at a novel site, Ser20. Phosphorylation at Ser15, -20 and -33
      can occur within minutes of DNA damage. Interestingly, while the DNA-binding
      activities of p53 appear to be dispensable, efficient phosphorylation at these
      three sites requires the tetramerization domain of p53. Substitution of an
      artificial tetramerization domain for this region also permits phosphorylation at
      the N-terminus, suggesting that oligomerization is important for DNA damage
      induced signalling to p53.

PMID- 10202146
TI  - Oncogenic Ras inhibits Fas ligand-mediated apoptosis by downregulating the
      expression of Fas.
AB  - Tumor growth is the result of deregulated tissue homeostasis which is maintained
      through the delicate balance of cell growth and apoptosis. One of the most
      efficient inducers of apoptosis is the death receptor Fas. We report here that
      oncogenic Ras (H-Ras) downregulates Fas expression and renders cells of
      fibroblastic and epitheloid origin resistant to Fas ligand-induced apoptosis. In
      Ras-transformed cells, Fas mRNA is absent. Inhibition of DNA methylation restores
      Fas expression. H-Ras signals via the PI 3-kinase pathway to downregulate Fas,
      suggesting that the known anti-apoptotic effect of the downstream PKB/Akt kinase
      may be mediated, at least in part, by the repression of Fas expression. Thus, the
      oncogenic potential of H-ras may reside on its capacity not only to promote
      cellular proliferation, but also to simultaneously inhibit Fas-triggered
      apoptosis.

PMID- 10202147
TI  - Phosphorylation of Tyr319 in ZAP-70 is required for T-cell antigen receptor
      dependent phospholipase C-gamma1 and Ras activation.
AB  - Accumulating evidence indicates that the interdomain B regions of ZAP-70 and Syk
      play pivotal roles in the coupling of T-cell antigen receptor (TCR) stimulation
      to the activation of downstream signaling pathways. The interdomain B region of
      ZAP-70 contains at least three candidate sites of tyrosine phosphorylation. In
      this report, we identify Tyr319 as a functionally important phosphorylation site
      in the ZAP-70 interdomain B region. TCR crosslinkage triggered a rapid increase
      in the phosphorylation of Tyr319 in Jurkat T cells. Although mutation of Tyr319
      to Phe had no effect on the tyrosine kinase activity of ZAP-70, the resulting
      ZAP(Y319-->F) mutant failed to reconstitute TCR-dependent Ca2+ mobilization, Ras
      activation, CD69 expression and NFAT-dependent transcription in ZAP-70-deficient
      Jurkat cells. These defects were correlated with reduced tyrosine phosphorylation
      of phospholipase C (PLC)-gamma1 and the LAT adapter protein in the ZAP(Y319-->F)
      expressing cells. On the other hand, ZAP(Y319-->F)-expressing cells displayed
      normal increases in SLP-76 phosphorylation and ERK activation during TCR
      stimulation. Phosphorylation of Tyr319 promoted the association of ZAP-70 with
      the SH2 domains of two key signaling molecules, Lck and PLC-gamma1. These studies
      suggest that Tyr319 phosphorylation is required for the assembly of a ZAP-70
      containing signaling complex that leads to the activation of the PLC-gamma1- and
      Ras-dependent signaling cascades in antigen-stimulated T cells.

PMID- 10202149
TI  - Cloning and characterization of a cDNA encoding an A-kinase anchoring protein
      located in the centrosome, AKAP450.
AB  - A combination of protein kinase A type II (RII) overlay screening, database
      searches and PCR was used to identify a centrosomal A-kinase anchoring protein. A
      cDNA with an 11.7 kb open reading frame was characterized and found to correspond
      to 50 exons of genomic sequence on human chromosome 7q21-22. This cDNA clone
      encoded a 3908 amino acid protein of 453 kDa, that was designated AKAP450
      (DDBJ/EMBL/GenBank accession No. AJ131693). Sequence comparison demonstrated that
      the open reading frame contained a previously characterized cDNA encoding Yotiao,
      as well as the human homologue of AKAP120. Numerous coiled-coil structures were
      predicted from AKAP450, and weak homology to pericentrin, giantin and other
      structural proteins was observed. A putative RII-binding site was identified
      involving amino acid 2556 of AKAP450 by mutation analysis combined with RII
      overlay and an amphipatic helix was predicted in this region. Immunoprecipitation
      of RII from RIPA-buffer extracts of HeLa cells demonstrated co-precipitation of
      AKAP450. By immunofluorecent labeling with specific antibodies it was
      demonstrated that AKAP450 localized to centrosomes. Furthermore, AKAP450 was
      shown to co-purify in centrosomal preparations. The observation of two mRNAs and
      several splice products suggests additional functions for the AKAP450 gene.

PMID- 10202148
TI  - Defective IL-12 production in mitogen-activated protein (MAP) kinase kinase 3
      (Mkk3)-deficient mice.
AB  - The p38 mitogen-activated protein kinase (MAPK) pathway, like the c-Jun N
      terminal kinase (JNK) MAPK pathway, is activated in response to cellular stress
      and inflammation and is involved in many fundamental biological processes. To
      study the role of the p38 MAPK pathway in vivo, we have used homologous
      recombination in mice to inactivate the Mkk3 gene, one of the two specific MAPK
      kinases (MAPKKs) that activate p38 MAPK. Mkk3(-/-) mice were viable and fertile;
      however, they were defective in interleukin-12 (IL-12) production by macrophages
      and dendritic cells. Interferon-gamma production following immunization with
      protein antigens and in vitro differentiation of naive T cells is greatly
      reduced, suggesting an impaired type I cytokine immune response. The effect of
      the p38 MAPK pathway on IL-12 expression is at least partly transcriptional,
      since inhibition of this pathway blocks IL-12 p40 promoter activity in macrophage
      cell lines and IL-12 p40 mRNA is reduced in MKK3-deficient mice. We conclude that
      the p38 MAP kinase, activated through MKK3, is required for the production of
      inflammatory cytokines by both antigen-presenting cells and CD4(+) T cells.

PMID- 10202150
TI  - Speedy: a novel cell cycle regulator of the G2/M transition.
AB  - Stage VI Xenopus oocytes are suspended at the G2/M transition of meiosis I, and
      represent an excellent system for the identification and examination of cell
      cycle regulatory proteins. Essential cell cycle regulators such as MAPK, cyclins
      and mos have the ability to induce oocyte maturation, causing the resumption of
      the cell cycle from its arrested state. We have identified the product of a novel
      Xenopus gene, Speedy or Spy1, which is able to induce rapid maturation of Xenopus
      oocytes, resulting in the induction of germinal vesicle breakdown (GVBD) and
      activation of M-phasepromoting factor (MPF). Spy1 activates the MAPK pathway in
      oocytes, and its ability to induce maturation is dependent upon this pathway.
      Spy1-induced maturation occurs much more rapidly than maturation induced by other
      cell cycle regulators including progesterone, mos or Ras, and does not require
      any of these proteins or hormones, indicating that Spy1-induced maturation
      proceeds through a novel regulatory pathway. In addition, we have shown that Spy1
      physically interacts with cdk2, and prematurely activates cdk2 kinase activity.
      Spy1 therefore represents a novel cell cycle regulatory protein, inducing
      maturation through the activation of MAPK and MPF, and also leading to the
      premature activation of cdk2.

PMID- 10202151
TI  - Timing of cyclin E gene expression depends on the regulated association of a
      bipartite repressor element with a novel E2F complex.
AB  - Transient induction of the cyclin E gene in late G1 gates progression into S. We
      show that this event is controlled via a cyclin E repressor module (CERM), a
      novel bipartite repressor element located near the cyclin E transcription start
      site. CERM consists of a variant E2F-binding site and a contiguous upstream AT
      rich sequence which cooperate during G0/G1 to delay cyclin E expression until
      late G1. CERM binds the protein complex CERC, which disappears upon progression
      through G0-G1 and reappears upon entry into the following G1. CERC disappearance
      correlates kinetically with the liberation of the CERM module in vivo and cyclin
      E transcriptional induction. CERC contains E2F4/DP1 and a pocket protein, and
      sediments faster than classical E2F complexes in a glycerol gradient, suggesting
      the presence of additional components in a novel high molecular weight complex.
      Affinity purified CERC binds to CERM but not to canonical E2F sites, thus
      displaying behavior different from known E2F complexes. In cells nullizygous for
      members of the Rb family, CERC is still detectable and CERM-dependent repression
      is functional. Thus p130, p107 and pRb function interchangeably in CERC. Notably,
      the CERC-CERM complex dissociates prematurely in pRb-/- cells in correspondence
      with the premature expression of cyclin E. Thus, we identify a new regulatory
      module that controls repression of G1-specific genes in G0/G1.

PMID- 10202152
TI  - Phosphorylation by G1-specific cdk-cyclin complexes activates the nucleolar
      transcription factor UBF.
AB  - Transcription of rRNA genes by RNA polymerase I increases following serum
      stimulation of quiescent NIH 3T3 fibroblasts. To elucidate the mechanism
      underlying transcriptional activation during progression through the G1 phase of
      the cell cycle, we have analyzed the activity and phosphorylation pattern of the
      nucleolar transcription factor upstream binding factor (UBF). Using a combination
      of tryptic phosphopeptide mapping and site-directed mutagenesis, we have
      identified Ser484 as a direct target for cyclin-dependent kinase 4 (cdk4)-cyclin
      D1- and cdk2-cyclin E-directed phosphorylation. Mutation of Ser484 impairs rDNA
      transcription in vivo and in vitro. The data demonstrate that UBF is regulated in
      a cell cycle-dependent manner and suggest a link between G1 cdks-cyclins, UBF
      phosphorylation and rDNA transcription activation.

PMID- 10202153
TI  - Mice deficient in the steroid receptor co-activator 1 (SRC-1) are resistant to
      thyroid hormone.
AB  - Steroid receptor co-activator 1 (SRC-1) is a transcription co-factor that
      enhances the hormone-dependent action, mediated by the thyroid hormone (TH)
      receptor (TR) and other nuclear receptors. In vitro studies have shown that SRC-1
      is necessary for the full expression of TH effect. SRC-1 knockout mice (SRC-1(-/
      )) provide a model to examine the role of this co-activator on TH action in vivo.
      At baseline, SRC-1(-/-) mice display resistance to TH (RTH) as evidenced by a 2.5
      fold elevation of serum TSH levels, despite a 50% increase in serum free TH
      levels as compared with wild-type (SRC-1(+/+)) mice. When mice were made
      hypothyroid, TSH levels increased, obliterating the difference between SRC-1(+/+)
      and SRC-1(-/-) mice observed at baseline. In contrast, the decline of TSH by
      treatment with L-triiodothyronine was severely blunted in SRC-1(-/-) mice. These
      data indicate that SRC-1 is not required for the upregulation of TSH in TH
      deficiency. However, SRC-1 enhances the sensitivity of TSH downregulation by TH.
      This is the first demonstration of RTH caused by a deficient co-factor other than
      TR. It supports the hypothesis that a putative defect in the SRC-1 gene or
      another co-factor could be the cause of RTH in humans without mutations in the TR
      genes.

PMID- 10202154
TI  - Molecular mechanisms of transcription activation by HLF and HIF1alpha in response
      to hypoxia: their stabilization and redox signal-induced interaction with
      CBP/p300.
AB  - Hypoxia-inducible factor 1 alpha (HIF1alpha) and its related factor, HLF,
      activate expression of a group of genes such as erythropoietin in response to low
      oxygen. Transfection analysis using fusion genes of GAL4DBD with various
      fragments of the two factors delineated two transcription activation domains
      which are inducible in response to hypoxia and are localized in the C-terminal
      half. Their sequences are conserved between HLF and HIF1alpha. One is designated
      NAD (N-terminal activation domain), while the other is CAD (C-terminal activation
      domain). Immunoblot analysis revealed that NADs, which were rarely detectable at
      normoxia, became stabilized and accumulated at hypoxia, whereas CADs were
      constitutively expressed. In the mammalian two-hybrid system, CAD and NAD baits
      enhanced the luciferase expression from a reporter gene by co-transfection with
      CREB-binding protein (CBP) prey, whereas CAD, but not NAD, enhanced beta
      galactosidase expression in yeast by CBP co-expression, suggesting that NAD and
      CAD interact with CBP/p300 by a different mechanism. Co-transfection experiments
      revealed that expression of Ref-1 and thioredoxin further enhanced the luciferase
      activity expressed by CAD, but not by NAD. Amino acid replacement in the
      sequences of CADs revealed a specific cysteine to be essential for their hypoxia
      inducible interaction with CBP. Nuclear translocation of thioredoxin from
      cytoplasm was observed upon reducing O2 concentrations.

PMID- 10202155
TI  - MyoD stimulates delta-1 transcription and triggers notch signaling in the Xenopus
      gastrula.
AB  - The Notch signaling cascade is involved in many developmental decisions, a
      paradigm of which has been the selection between epidermal and neural cell fates
      in both invertebrates and vertebrates. Notch has also been implicated as a
      regulator of myogenesis, although its precise function there has remained
      controversial. Here we show that the muscle-determining factor MyoD is a direct,
      positive regulator of the Notch ligand Delta-1 in prospective myoblasts of the
      pre-involuted mesoderm in Xenopus gastrulae. Injection of a dominant MyoD
      repressor variant ablates mesodermal Delta-1 expression in vivo. Furthermore,
      MyoD-dependent Delta-1 induction is sufficient to activate transcription from
      promoters of E(spl)-related genes in a Notch-dependent manner. These results
      indicate that a hallmark of neural cell fate determination, i.e. the feedback
      loop between differentiation promoting basic helix-loop-helix proteins and the
      Notch regulatory circuitry, is conserved in myogenesis, supporting a direct
      involvement of Notch in muscle determination.

PMID- 10202156
TI  - Functional mammalian homologues of the Drosophila PEV-modifier Su(var)3-9 encode
      centromere-associated proteins which complex with the heterochromatin component
      M31.
AB  - The chromo and SET domains are conserved sequence motifs present in chromosomal
      proteins that function in epigenetic control of gene expression, presumably by
      modulating higher order chromatin. Based on sequence information from the SET
      domain, we have isolated human (SUV39H1) and mouse (Suv39h1) homologues of the
      dominant Drosophila modifier of position-effect-variegation (PEV) Su(var)3-9.
      Mammalian homologues contain, in addition to the SET domain, the characteristic
      chromo domain, a combination that is also preserved in the Schizosaccharyomyces
      pombe silencing factor clr4. Chromatin-dependent gene regulation is demonstrated
      by the potential of human SUV39H1 to increase repression of the pericentromeric
      white marker gene in transgenic flies. Immunodetection of endogenous
      Suv39h1/SUV39H1 proteins in a variety of mammalian cell lines reveals enriched
      distribution at heterochromatic foci during interphase and centromere-specific
      localization during metaphase. In addition, Suv39h1/SUV39H1 proteins associate
      with M31, currently the only other characterized mammalian SU(VAR) homologue.
      These data indicate the existence of a mammalian SU(VAR) complex and define
      Suv39h1/SUV39H1 as novel components of mammalian higher order chromatin.

PMID- 10202157
TI  - Modulation of exon skipping by high-affinity hnRNP A1-binding sites and by intron
      elements that repress splice site utilization.
AB  - The RNA-binding protein hnRNP A1 is a splicing regulator produced by exclusion of
      alternative exon 7B from the A1 pre-mRNA. Each intron flanking exon 7B contains a
      high-affinity A1-binding site. The A1-binding elements promote exon skipping in
      vivo, activate distal 5' splice site selection in vitro and improve the
      responsiveness of pre-mRNAs to increases in the concentration of A1. Whereas the
      glycine-rich C-terminal domain of A1 is not required for binding, it is essential
      to activate the distal 5' splice site. Because A1 complexes can interact
      simultaneously with two A1-binding sites, we propose that an interaction between
      bound A1 proteins facilitates the pairing of distant splice sites. Based on the
      distribution of putative A1-binding sites in various pre-mRNAs, an A1-mediated
      change in pre-mRNA conformation may help define the borders of mammalian introns.
      We also identify an intron element which represses the 3' splice site of exon 7B.
      The activity of this element is mediated by a factor distinct from A1. Our
      results suggest that exon 7B skipping results from the concerted action of
      several intron elements that modulate splice site recognition and pairing.

PMID- 10202158
TI  - TAP binds to the constitutive transport element (CTE) through a novel RNA-binding
      motif that is sufficient to promote CTE-dependent RNA export from the nucleus.
AB  - The constitutive transport element (CTE) of the simian type D retroviruses
      overcomes nuclear retention and allows nuclear export of unspliced viral RNAs by
      recruiting TAP, a host factor which is thought to be required for export of
      cellular mRNAs. In this report, we show that the first 372 amino acid residues of
      TAP, comprising a stretch of leucine-rich repeats, are both necessary and
      sufficient for binding to the CTE RNA and promoting its export to the cytoplasm.
      Moreover, like the full-length protein, this domain migrates to the cytoplasm
      upon nuclear co-injection with the CTE RNA. Together, these results indicate that
      the CTE-binding domain includes the signals for nuclear export. We also describe
      a derivative of TAP that bears a triple amino acid substitution within the CTE
      binding domain and substantially reduces the export of mRNAs from the nucleus.
      This provides further evidence for a role for TAP in this process. Thus, the CTE
      binding domain of TAP defines a novel RNA-binding motif which has dual functions,
      both recognizing the CTE RNA and interacting with other components of the nuclear
      transport machinery.

PMID- 10202159
TI  - Sequence interval within the PEST motif of Bicoid is important for translational
      repression of caudal mRNA in the anterior region of the Drosophila embryo.
AB  - The Drosophila body organizer Bicoid (Bcd) is a maternal homeodomain protein. It
      forms a concentration gradient along the longitudinal axis of the preblastoderm
      embryo and activates early zygotic segmentation genes in a threshold-dependent
      fashion. In addition, Bcd acts as a translational repressor of maternal caudal
      (cad) mRNA in the anterior region of the embryo. This process involves a distinct
      Bcd-binding region (BBR) in the 3' untranslated region (UTR) of cad mRNA. Using
      cotransfection assays, we found that Bcd represses translation in a cap-dependent
      manner. Bcd-dependent translational repression involves a portion of the PEST
      motif of Bcd, a conserved protein motif best known for its function in protein
      degradation. Rescue experiments with Bcd-deficient embryos expressing transgene
      derived Bcd mutants indicate that amino acid replacements within the C-terminal
      portion of the PEST motif prevent translational repression of cad mRNA but allow
      for Bcd-dependent transcriptional activation. Thus, Bcd contains separable
      protein domains for transcriptional and translational regulation of target genes.
      Maternally-derived cad protein in the anterior region of embryos interferes with
      head morphogenesis, showing that cad mRNA suppression by Bcd is an important
      control event during early Drosophila embryogenesis.

PMID- 10202160
TI  - Translation termination efficiency can be regulated in Saccharomyces cerevisiae
      by environmental stress through a prion-mediated mechanism.
AB  - [PSI+] is a protein-based heritable phenotype of the yeast Saccharomyces
      cerevisiae which reflects the prion-like behaviour of the endogenous Sup35p
      protein release factor. [PSI+] strains exhibit a marked decrease in translation
      termination efficiency, which permits decoding of translation termination signals
      and, presumably, the production of abnormally extended polypeptides. We have
      examined whether the [PSI+]-induced expression of such an altered proteome might
      confer some selective growth advantage over [psi-] strains. Although otherwise
      isogenic [PSI+] and [psi-] strains show no difference in growth rates under
      normal laboratory conditions, we demonstrate that [PSI+] strains do exhibit
      enhanced tolerance to heat and chemical stress, compared with [psi-] strains.
      Moreover, we also show that the prion-like determinant [PSI+] is able to regulate
      translation termination efficiency in response to environmental stress, since
      growth in the presence of ethanol results in a transient increase in the
      efficiency of translation termination and a loss of the [PSI+] phenotype. We
      present a model to describe the prion-mediated regulation of translation
      termination efficiency and discuss its implications in relation to the potential
      physiological role of prions in S.cerevisiae and other fungi.

PMID- 10202161
TI  - Nup153 is an M9-containing mobile nucleoporin with a novel Ran-binding domain.
AB  - We employed a phage display system to search for proteins that interact with
      transportin 1 (TRN1), the import receptor for shuttling hnRNP proteins with an M9
      nuclear localization sequence (NLS), and identified a short region within the N
      terminus of the nucleoporin Nup153 which binds TRN1. Nup153 is located at the
      nucleoplasmic face of the nuclear pore complex (NPC), in the distal basket
      structure, and functions in mRNA export. We show that this Nup153 TRN1
      interacting region is an M9 NLS. We found that both import and export receptors
      interact with several regions of Nup153, in a RanGTP-regulated fashion. RanGTP
      dissociates Nup153-import receptor complexes, but is required for Nup153-export
      receptor interactions. We also show that Nup153 is a RanGDP-binding protein, and
      that the interaction is mediated by the zinc finger region of Nup153. This
      represents a novel Ran-binding domain, which we term the zinc finger Ran-binding
      motif. We provide evidence that Nup153 shuttles between the nuclear and
      cytoplasmic faces of the NPC. The presence of an M9 shuttling domain in Nup153,
      together with its ability to move within the NPC and to interact with export
      receptors, suggests that this nucleoporin is a mobile component of the pore which
      carries export cargos towards the cytoplasm.

PMID- 10202162
TI  - The prenylation status of a novel plant calmodulin directs plasma membrane or
      nuclear localization of the protein.
AB  - Post-translational attachment of isoprenyl groups to conserved cysteine residues
      at the C-terminus of a number of regulatory proteins is important for their
      function and subcellular localization. We have identified a novel calmodulin,
      CaM53, with an extended C-terminal basic domain and a CTIL CaaX-box motif which
      are required for efficient prenylation of the protein in vitro and in vivo.
      Ectopic expression of wild-type CaM53 or a non-prenylated mutant protein in
      plants causes distinct morphological changes. Prenylated CaM53 associates with
      the plasma membrane, but the non-prenylated mutant protein localizes to the
      nucleus, indicating a dual role for the C-terminal domain. The subcellular
      localization of CaM53 can be altered by a block in isoprenoid biosynthesis or
      sugar depletion, suggesting that CaM53 activates different targets in response to
      metabolic changes. Thus, prenylation of CaM53 appears to be a novel mechanism by
      which plant cells can coordinate Ca2+ signaling with changes in metabolic
      activities.

PMID- 10202163
TI  - DNA binding of Xrcc4 protein is associated with V(D)J recombination but not with
      stimulation of DNA ligase IV activity.
AB  - Mammalian cells are protected from the effects of DNA double-strand breaks by end
      joining repair. Cells lacking the Xrcc4 protein are hypersensitive to agents that
      induce DNA double-strand breaks, and are unable to complete V(D)J recombination.
      The residual repair of broken DNA ends in XRCC4-deficient cells requires short
      sequence homologies, thus possibly implicating Xrcc4 in end alignment. We show
      that Xrcc4 binds DNA, and prefers DNA with nicks or broken ends. Xrcc4 also binds
      to DNA ligase IV and enhances its joining activity. This stimulatory effect is
      shown to occur at the adenylation of the enzyme. DNA binding of Xrcc4 is
      correlated with its complementation of the V(D)J recombination defects in XRCC4
      deficient cells, but is not required for stimulation of DNA ligase IV. Thus, the
      ability of Xrcc4 to bind to DNA suggests functions independent of DNA ligase IV.

PMID- 10202165
TI  - Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced
      cervical cancer.
AB  - BACKGROUND AND METHODS: On behalf of the Gynecologic Oncology Group, we performed
      a randomized trial of radiotherapy in combination with three concurrent
      chemotherapy regimens -- cisplatin alone; cisplatin, fluorouracil, and
      hydroxyurea; and hydroxyurea alone -- in patients with locally advanced cervical
      cancer. Women with primary untreated invasive squamous-cell carcinoma,
      adenosquamous carcinoma, or adenocarcinoma of the cervix of stage IIB, III, or
      IVA, without involvement of the para-aortic lymph nodes, were enrolled. The
      patients had to have a leukocyte count of at least 3000 per cubic millimeter, a
      platelet count of at least 100,000 per cubic millimeter, a serum creatinine level
      no higher than 2 mg per deciliter (177 micromol per liter), and adequate hepatic
      function. All patients received external-beam radiotherapy according to a strict
      protocol. Patients were randomly assigned to receive one of three chemotherapy
      regimens: 40 mg of cisplatin per square meter of body-surface area per week for
      six weeks (group 1); 50 mg of cisplatin per square meter on days 1 and 29,
      followed by 4 g of fluorouracil per square meter given as a 96-hour infusion on
      days 1 and 29, and 2 g of oral hydroxyurea per square meter twice weekly for six
      weeks (group 2); or 3 g of oral hydroxyurea per square meter twice weekly for six
      weeks (group 3). RESULTS: The analysis included 526 women. The median duration of
      follow-up was 35 months. Both groups that received cisplatin had a higher rate of
      progression-free survival than the group that received hydroxyurea alone (P<0.001
      for both comparisons). The relative risks of progression of disease or death were
      0.57 (95 percent confidence interval, 0.42 to 0.78) in group 1 and 0.55 (95
      percent confidence interval, 0.40 to 0.75) in group 2, as compared with group 3.
      The overall survival rate was significantly higher in groups 1 and 2 than in
      group 3, with relative risks of death of 0.61 (95 percent confidence interval,
      0.44 to 0.85) and 0.58 (95 percent confidence interval, 0.41 to 0.81),
      respectively. CONCLUSIONS: Regimens of radiotherapy and chemotherapy that contain
      cisplatin improve the rates of survival and progression-free survival among women
      with locally advanced cervical cancer.

PMID- 10202164
TI  - Pelvic radiation with concurrent chemotherapy compared with pelvic and para
      aortic radiation for high-risk cervical cancer.
AB  - BACKGROUND AND METHODS: We compared the effect of radiotherapy to a pelvic and
      para-aortic field with that of pelvic radiation and concurrent chemotherapy with
      fluorouracil and cisplatin in women with advanced cervical cancer. Between 1990
      and 1997, 403 women with advanced cervical cancer confined to the pelvis (stages
      IIB through IVA or stage IB or IIa with a tumor diameter of at least 5 cm or
      involvement of pelvic lymph nodes) were randomly assigned to receive either 45 Gy
      of radiation to the pelvis and para-aortic lymph nodes or 45 Gy of radiation to
      the pelvis alone plus two cycles of fluorouracil and cisplatin (days 1 through 5
      and days 22 through 26 of radiation). Patients were then to receive one or two
      applications of low-dose-rate intracavitary radiation, with a third cycle of
      chemotherapy planned for the second intracavitary procedure in the combined
      therapy group. RESULTS: Of the 403 eligible patients, 193 in each group could be
      evaluated. The median duration of follow-up was 43 months. Estimated cumulative
      rates of survival at five years were 73 percent among patients treated with
      radiotherapy and chemotherapy and 58 percent among patients treated with
      radiotherapy alone (P=0.004). Cumulative rates of disease-free survival at five
      years were 67 percent among patients in the combined-therapy group and 40 percent
      among patients in the radiotherapy group (P<0.001). The rates of both distant
      metastases (P<0.001) and locoregional recurrences (P<0.001) were significantly
      higher among patients treated with radiotherapy alone. The seriousness of side
      effects was similar in the two groups, with a higher rate of reversible
      hematologic effects in the combined-therapy group. CONCLUSIONS: The addition of
      chemotherapy with fluorouracil and cisplatin to treatment with external-beam and
      intracavitary radiation significantly improved survival among women with locally
      advanced cervical cancer.

PMID- 10202166
TI  - Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and
      adjuvant hysterectomy for bulky stage IB cervical carcinoma.
AB  - BACKGROUND: Bulky stage IB cervical cancers have a poorer prognosis than smaller
      stage I cervical cancers. For the Gynecologic Oncology Group, we conducted a
      trial to determine whether weekly infusions of cisplatin during radiotherapy
      improve progression-free and overall survival among patients with bulky stage IB
      cervical cancer. METHODS: Women with bulky stage IB cervical cancers (tumor, > or
      =4 cm in diameter) were randomly assigned to receive radiotherapy alone or in
      combination with cisplatin (40 mg per square meter of body-surface area once a
      week for up to six doses; maximal weekly dose, 70 mg), followed in all patients
      by adjuvant hysterectomy. Women with evidence of lymphadenopathy on computed
      tomographic scanning or lymphangiography were ineligible unless histologic
      analysis showed that there was no lymph-node involvement. The cumulative dose of
      external pelvic and intracavitary radiation was 75 Gy to point A (cervical
      parametrium) and 55 Gy to point B (pelvic wall). Cisplatin was given during
      external radiotherapy, and adjuvant hysterectomy was performed three to six weeks
      later. RESULTS: The relative risks of progression of disease and death among the
      183 women assigned to receive radiotherapy and chemotherapy with cisplatin, as
      compared with the 186 women assigned to receive radiotherapy alone, were 0.51 (95
      percent confidence interval, 0.34 to 0.75) and 0.54 (95 percent confidence
      interval, 0.34 to 0.86), respectively. The rates of both progression-free
      survival (P<0.001) and overall survival (P=0.008) were significantly higher in
      the combined-therapy group at four years. In the combined-therapy group there
      were higher frequencies of transient grade 3 (moderate) and grade 4 (severe)
      adverse hematologic effects (21 percent, vs. 2 percent in the radiotherapy group)
      and adverse gastrointestinal effects (14 percent vs. 5 percent). CONCLUSIONS:
      Adding weekly infusions of cisplatin to pelvic radiotherapy followed by
      hysterectomy significantly reduced the risk of disease recurrence and death in
      women with bulky stage IB cervical cancers.

PMID- 10202167
TI  - Temporal trends in cardiogenic shock complicating acute myocardial infarction.
AB  - BACKGROUND: Limited information is available on trends in the incidence of and
      mortality due to cardiogenic shock complicating acute myocardial infarction. We
      studied the incidence of cardiogenic shock complicating acute myocardial
      infarction and in-hospital death rates among patients with this condition in a
      single community from 1975 through 1997. METHODS: We conducted an observational
      study of 9076 residents of metropolitan Worcester, Massachusetts, who were
      hospitalized with confirmed acute myocardial infarction in all local hospitals
      during 11 one-year periods between 1975 and 1997. Our study included periods
      before and after the advent of reperfusion therapy. RESULTS: The incidence of
      cardiogenic shock remained relatively stable over time, averaging 7.1 percent
      among patients with acute myocardial infarction. The results of a multivariable
      regression analysis indicated that the patients hospitalized during recent study
      years were not at a substantially lower risk for shock than patients hospitalized
      in the mid-to-late 1970s. Patients in whom cardiogenic shock developed had a
      significantly greater risk of dying during hospitalization (71.7 percent) than
      those who did not have cardiogenic shock (12.0 percent, P<0.001). A significant
      trend toward an increase in in-hospital survival among patients with cardiogenic
      shock in the mid-to-late 1990s was found in crude and adjusted analyses.
      CONCLUSIONS: Our findings indicate no significant change in the incidence of
      cardiogenic shock complicating acute myocardial infarction over a 23-year period.
      However, the short-term survival rate has increased in recent years at the same
      time as the use of coronary reperfusion strategies has increased.

PMID- 10202169
TI  - Images in clinical medicine. Cerebral histoplasmosis.

PMID- 10202168
TI  - Clinical features of 52 neonates with hyperinsulinism.
AB  - BACKGROUND: Neonatal hyperinsulinemic hypoglycemia is often resistant to medical
      therapy and is often treated with near-total pancreatectomy. However, the
      pancreatic lesions may be focal and treatable by partial pancreatic resection.
      METHODS: We studied 52 neonates with hyperinsulinism who were treated surgically.
      The type and location of the pancreatic lesions were determined by preoperative
      pancreatic catheterization and intraoperative histologic studies. Partial
      pancreatectomy was performed in infants with focal lesions, and near-total
      pancreatectomy was performed in those with diffuse lesions. The postoperative
      outcome was determined by measurements of plasma glucose and glycosylated
      hemoglobin and by oral glucose-tolerance tests. RESULTS: Thirty neonates had
      diffuse beta-cell hyperfunction, and 22 had focal adenomatous islet-cell
      hyperplasia. Among the latter, the lesions were in the head of the pancreas in
      nine, the isthmus in three, the body in eight, and the tail in two. The clinical
      manifestations were similar in both groups. The infants with focal lesions had no
      symptoms of hypoglycemia and had normal preprandial and postprandial plasma
      glucose and glycosylated hemoglobin values and normal results on oral glucose
      tolerance tests after partial pancreatectomy (performed in 19 of 22 neonates). By
      contrast, after near-total pancreatectomy, 13 of the patients with diffuse
      lesions had persistent hypoglycemia, type 1 diabetes mellitus developed in 8, and
      hyperglycemia developed in another 7; overall, only 2 patients with diffuse
      lesions had normal plasma glucose concentrations in the first year after surgery.
      CONCLUSIONS: Among neonates with hyperinsulinism, about half may have focal islet
      cell hyperplasia that can be treated with partial pancreatectomy. These neonates
      can be identified through pancreatic catheterization and intraoperative
      histologic studies.

PMID- 10202170
TI  - Genetic disorders of renal electrolyte transport.

PMID- 10202171
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 11-1999. A 60-year-old woman with epidural and paraspinal masses.

PMID- 10202172
TI  - Improved treatment for cervical cancer--concurrent chemotherapy and radiotherapy.

PMID- 10202173
TI  - The causes of neonatal hypoglycemia.

PMID- 10202174
TI  - Disease management--promises and pitfalls.

PMID- 10202176
TI  - In vivo induction of pyrimidine dimers in human skin by UVA radiation: initiation
      of cell damage and/or intercellular communication?
AB  - Pyrimidine dimers participate as important factors in ultraviolet-induced
      lethality, mutagenicity and tumorgenicity. Substantial efforts have been made in
      recent years to understand the induction of pyrimidine photodimers and their
      repair in human skin cells exposed to low physiological fluences of UV-light.
      Dimers are known to be efficiently induced after UVC and UVB irradiation, but
      these photoproducts are also highly induced in DNA isolated from human skin
      irradiated with UVA. By using a sensitive immunohistochemistry dimer detection
      assay, we confirm that in vivo UVA radiation induces substantial amounts of these
      DNA changes in the epidermis; in addition, this technique detects them far into
      the reticular dermis. A considerable number of these photodimers were also seen
      in non-irradiated control skin up to two centimeters from the irradiation site.
      All the lesions persist for at least two days post-irradiation. These results
      sustain the hypothesis that pyrimidine dimer formation and excision could be a
      modality of epidermal communication.

PMID- 10202175
TI  - Pharmacology of N-type Ca2+ channels distributed in cardiovascular system
      (Review).
AB  - Irregular functions in Ca2+ channels are intimately involved in many aspects of
      cardiovascular diseases. We can obtain a wide variety of L-type Ca2+ channel
      antagonists to treat hypertension and angina pectoris. Dihydropyridines (DHPs)
      have, first of all, been extensively developed due to their high selectivity for
      L-type Ca2+ channel and safety in pharmacological aspects. In contrast, many
      lines of evidence suggest that clinical efficacy of those DHPs are limited and
      undesirable effects are sometimes observed because of the specific distribution
      of L-type Ca2+ channels. As well as the L-type, peripherally distributed N-type
      Ca2+ channel plays a key role in cardiovascular regulation through autonomic
      nervous system. Recently, we developed a unique DHP derivative, cilnidipine
      (FRC8653) which has a dual antagonistic action on both L-type and N-type Ca2+
      channels. Our recent studies with this DHP have made it clear that the N-type
      Ca2+ channel is also a new therapeutic target in cardiovascular diseases. We
      review the recent advances in pharmacology of the N-type Ca2+ channel and
      therapeutic implications of their antagonists.

PMID- 10202177
TI  - Cell-dependent function of HIV-1 Vif for virus replication (Review).
AB  - It has been well established that the Vif protein of human immunodeficiency virus
      type 1 (HIV-1) acts late in the viral life cycle and increases the infectivity of
      the progeny virions in a producer cell-dependent manner. The virions produced in
      the absence of Vif in non-permissive cells (Delta Vif) are defective for a
      step(s) before and/or during reverse transcription. In this review, the
      functional and structural analyses of these virions including our new data are
      summarized.

PMID- 10202178
TI  - Differential induction of interferon (IFN)-inducible protein 10 following
      differentiation of a monocyte, macrophage cell lineage is related to the changes
      of nuclear proteins bound to IFN stimulus response element and kappaB sites.
AB  - We examined chemokine gene expression following the differentiation of a
      monocyte, macrophage cell lineage. The human monoblastic cell line, U937 was
      differentiated to macrophages by the treatment with either phorbol 12-myristate
      13-acetate (PMA), retinoic acid (RA), or vitamin D3 (VitD3). The gene expression
      of interferon (IFN)-inducible protein 10 (IP-10) (a CXC chemokine) was markedly
      augmented by the IFNgamma treatment in PMA- or RA-differentiated U937 cells, but
      only marginally in undifferentiated or VitD3-treated cells. In contrast, another
      inducible gene expression of monocyte chemotactic protein-1 (a CC chemokine) and
      the activation of the transcriptional factor (FcRFgamma) bound to the gamma
      response region were similarly or less abundantly induced by IFNgamma treatment
      in PMA- or RA-differentiated U937 cells, indicating that increased IP-10 mRNA
      induction was not due to the augmented ability of the cells to respond to the
      presence of IFNgamma. Increased expression of IFNgamma-induced IP-10 mRNA
      following the differentiation of U937 cells was mediated largely by augmented
      transcriptional activity of the gene and was related to differentiation-dependent
      changes of the proteins bound to IFN stimulus response element (ISRE) and kB
      sites, suggesting that these nuclear proteins may determine the IP-10 mRNA
      inducibility by IFNgamma.

PMID- 10202179
TI  - Alpha-amylase functions as a salivary gland-specific self T cell epitope in
      patients with Sjogren's syndrome.
AB  - Analyses of T cell receptors (TCR) on T cells infiltrating labial salivary glands
      of patients with Sjogren's syndrome (SS) indicate that the cells expand by
      antigen stimulation in context of major histocompatibility complex (MHC). To
      elucidate the autoantigens recognized by T cells infiltrating in labial salivary
      glands from patients with SS, proteins derived from human salivary gland cDNA
      libraries were screened by West-Western method using TCR-CDR3 probe, which is
      antigen recognition region of TCR on T cells. 13 cDNA clones were detected as
      proteins binding to TCR-CDR3 region. One was a human alpha-amylase salivary
      precursor (AA54-407), suggesting that alpha-amylase might be a salivary gland
      specific autoantigen. To examine whether alpha-amylase acts as an antigen in
      labial salivary glands, PBL from 11 patients with SS were incubated with 9
      different synthetic amino acids of alpha-amylase or salivary alpha-amylase. SSCP
      analysis on TCR clearly showed that alpha-amylase reactive T cells were observed
      in labial salivary glands from 3 of 11 patients with SS (27%). These findings
      support the possibility that alpha-amylase functions as a salivary gland-specific
      T cell epitope and induces autoimmunity in SS.

PMID- 10202180
TI  - Are aberrant transcripts of FHIT, TSG101, and PTEN/MMAC1 oncogenesis related?
AB  - Tumor suppressor gene mutations in TSG101, FHIT, and PTEN/MMAC1 were found in
      many types of cancer and the defects in these genes are responsible for the tumor
      development. Since aberrant transcripts of these genes were also identified in
      normal tissues, the significance of these mutations in carcinogenesis has become
      a controversy. To determine large deletions or other alterations in these genes,
      we analyzed the integrity of their transcripts in both cancerous tissues and the
      matched normal tissues. More than 400 transcripts derived from at least eight
      different types of tissue were analyzed using nested RT-PCR and direct
      sequencing. High frequency of abnormal transcripts of all three genes occurred in
      both cancerous and the normal tissues. We believe that these aberrant transcripts
      do not relate to cancer development. These aberrant transcripts may be imperfect
      products of splicesome that occurs rarely but was amplified by nested RT-PCR.
      They may be also generated from alternative splicing due to the exonic splicing
      elements of the gene.

PMID- 10202181
TI  - OK-432 treatment increases matrix metalloproteinase-9 production and improves
      dimethylnitrosamine-induced liver cirrhosis in rats.
AB  - Kupffer cells are major matrix metalloproteinase-producing cells in the liver.
      The production of metalloproteinases in Kupffer cells may contribute to the
      improvement of liver fibrosis inducing liver cirrhosis. In this study, we
      examined the effect of the OK-432 (a biological response modifier) on the
      dimethylnitrosamine-induced liver cirrhosis in rats. Dimethylnitrosamine (10
      microg/ml) was injected intraperitoneally into 20 male Wistar rats 3x/week for 4
      weeks. For the subsequent 4 weeks, the animals were injected with saline (1 ml,
      1x/week) (Group I, n=10) or OK-432 (1 Klinishe Einheit, 1x/week) (Group II,
      n=10). The control rats were injected with 1 ml saline for the initial 4 weeks
      and subsequent 4 weeks (Group III, n=10). The degree of hepatic fibrosis, the
      immunolocalization of type IV collagen, hyaluronic acid, and alpha-smooth muscle
      actin, and the mRNA expression by Northern blotting and the activity by gelatin
      zymography of metalloproteinase-9 were evaluated. Serum aminotransferase,
      hyaluronic acid, interleukin-1beta and tumor necrosis factor-alpha levels were
      measured. The deposition of a-smooth muscle actin and extracellular matrix
      containing type IV collagen and hyaluronic acid was markedly suppressed by OK
      432. The mRNA expression and the activity of metalloproteinase-9 were markedly
      increased by OK-432. The serum aminotransferase and hyaluronic acid levels were
      decreased by OK-432. The serum interleukin-1 and tumor necrosis factor-alpha
      values were lower than the detectable limit in all samples from all three groups.
      These results indicate that OK-432 increased the production of metalloproteinase
      9 and improved the rat dimethylnitrosamine-induced liver cirrhosis. OK-432 is
      suggested to be useful for the treatment of liver cirrhosis.

PMID- 10202182
TI  - Enhancement of protein kinase activity in the cytosol of regenerating rat liver:
      regulatory role of endogenous regucalcin.
AB  - The effect of regucalcin, a Ca2+-binding protein, on protein kinase activity in
      the cytosol of regenerating rat liver was investigated. Protein phosphorylation
      was significantly increased in the liver cytosol obtained at 6, 24, and 48 h
      after a partial hepatectomy (about 65%) in comparison with that of sham-operated
      rats. This increase was significantly inhibited by the addition of
      trifluoperazine (2x10(-5) M), staurosporine (10(-7) M) or genistein (10(-5) M),
      which is an inhibitor of protein kinases, in the reaction mixture. The presence
      of regucalcin (0.1-0.5 microM) caused a significant decrease in protein
      phosphorylation in the cytosol from normal and regenerating rat livers. The
      effect of regucalcin (0.5 microM) was completely abolished by the addition of
      anti-regucalcin monoclonal antibody (50 ng/ml). The elevation of protein
      phosphorylation in regenerating rat liver was significantly enhanced by the
      presence of anti-regucalcin monoclonal antibody (50 ng/ml). The effect of
      regucalcin in decreasing protein phosphorylation in the cytosol of regenerating
      rat liver was not seen in the presence of the antibody. The present study
      demonstrates that protein kinase activity, is enhanced in the cytosol of
      regenerating rat liver, and that endogenous regucalcin has an inhibitory role in
      the enhancement of protein phosphorylation by various protein kinases.

PMID- 10202183
TI  - Lipodermatosclerosis and the significance of proteolytic remodeling in the
      pathogenesis of venous ulceration (Review).
AB  - The preceding stage of venous ulceration represents a scleroderma-like hardening
      of the skin called lipodermatosclerosis. Clinical stages such as
      lipodermatosclerosis and venous ulceration, which succeed one another are highly
      associated to chronic venous insufficiency. Lipodermatosclerosis is characterized
      by fibrous scar tissue of the reticular dermis built up of collagen bundles and
      loss of cellular components, whereas venous ulceration is characterized by total
      loss of epidermis and partially of matrix structures in the upper dermis. There
      is a growing recognition that an excessive proteolytic activity by proteases, in
      particular that of matrix metalloproteinases and fibrinolytic factors of the
      plasminogen activation system may be a key feature in the pathophysiological
      understanding of venous leg ulcer formation. Lipodermatosclerosis displays an
      intense ongoing proteolytic process by elevated matrix metalloproteinase
      activity, as recently shown on different molecular and biological levels.
      Elevated expression on mRNA and protein level of matrix metalloproteinases and
      fibrinolytic factors of the plasminogen activation system have been detected in
      liposclerotic skin lesions. In addition, matrix metalloproteinases were
      proteolytically activated confirmed by zymography experiments and collagen
      degradation assays. Therefore it is well conceivable, that proteolytic enzymes of
      matrix metalloproteinases could initiate an elevated turnover of the
      extracellular matrix with subsequent breakdown of the matrix scaffold finally
      resulting in venous ulceration.

PMID- 10202184
TI  - The mouse interferon-gamma transgene chronic hepatitis model (Review).
AB  - Acute hepatitis models are widely used for the evaluation of drugs for liver
      disease or for basic research on hepatitis. However, it is difficult to produce
      similar liver conditions to human chronic hepatitis with an acute hepatitis
      model. The interferon-gamma (IFN-gamma) transgenic mouse, which carries the mouse
      IFN-gamma gene, strongly expresses the IFN-gamma gene in the liver and develops
      chronic hepatitis from the age of 6-10 weeks. We found that the hepatitis in this
      mouse reflects human chronic hepatitis at least in the following points, i)
      infiltration by lymphoid cells into the portal areas and necroinflammation in the
      lobules, and ii) expression of Fas antigen and Fas ligand mRNAs in the liver.
      Furthermore, the induction of CPP32-like protease activity in the transgenic
      mouse liver suggests the involvement of this protease activity in the development
      of chronic hepatitis.

PMID- 10202185
TI  - Expression and characterization of protein kinase C in isolated rabbit parietal
      cells.
AB  - We investigated the expression, characterization and distribution of protein
      kinase C (PKC) isozymes in isolated rabbit parietal cells (PC). Cellular extracts
      of PC were analyzed by Western blot using isozyme-specific antibodies. The Ca2+
      independent PKC-epsilon was detected in cytosolic, membrane and cytoskeletal
      fractions of basal and histamine-stimulated PC, whereas the Ca2+-dependent PKC
      alpha was confined to the cytosolic and membrane fractions. Cytosolic and
      membrane fractions were partially purified by DEAE cellulose column
      chromatography with elution of increasing NaCl concentration. Eluates of 0.15 M
      and 0.3 M NaCl PC fractions were identified as PKC-alpha and -epsilon isoforms,
      respectively. Phorbol 12-myristate 13-acetate (TPA) treatment of PC for 15, 30
      and 60 sec decreased significantly cytosolic PKC-alpha and increased membrane
      associated PKC-alpha. In contrast to the distribution of PKC-alpha, TPA did not
      alter membrane or cytosolic level of PKC-epsilon. Comparison of the dose-response
      curves between TPA-induced hydrogen (H+) secretion, as measured by aminopyrine
      (AP) uptake, and the membrane-associated PKC-alpha suggests that translocation of
      PKC-alpha is not involved in the H+ secretory process in PC. Furthermore, a PKC
      inhibitor, staurosporine, produced a concentration-dependent enhancement of
      histamine-stimulated H+ secretion. These findings suggest that PKC-alpha plays a
      negative modulatory role, rather than an obligatory role, in H+ secretion. The
      localization and distribution of PKC-epsilon into the cytoskeletal fraction of PC
      also suggests that this isozyme may be involved in the cellular regulation of
      reversible morphological transformation during stimulation.

PMID- 10202186
TI  - Influenza virus overcomes apoptosis by rapid multiplication.
AB  - The kinetics of apoptotic fragmentation of the chromosomal DNA was determined in
      the influenza virus-infected MDCK, HeLa and KB cells, respectively. Comparison of
      these kinetics with the kinetics of virus multiplication revealed that the
      multiplication of influenza virus was observed only when apoptosis was induced
      after the production of progeny virus in the infected cells. The extent of
      apoptotic response was reversely correlated with the permissiveness of the cells.

PMID- 10202187
TI  - Expression of hepatocyte growth factor/scatter factor and its receptor c-Met in
      brain tumors: evidence for a role in progression of astrocytic tumors (Review).
AB  - Hepatocyte growth factor (HGF) is a multifunctional cytokine which is believed to
      have important roles in tissue development and regeneration, and tumor
      progression. It is indistinguishable from scatter factor (SF), a motility factor.
      HGF/SF is believed to be a mesenchymal cell-derived cytokine acting for
      epithelial cells bearing its receptor tyrosine kinase, c-Met. Recently, we found
      that glioblastoma multiforme (GBM), a highly malignant brain tumor of astrocytic
      origin, concomitantly express HGF/SF and c-Met. This finding indicates a presence
      of autocrine loop of HGF/SF signaling pathway in GBM. Moreover, GBM cells also co
      express HGF activator, a recently identified serine proteinase having efficient
      HGF/SF activating activity. The expression of HGF/SF and c-Met was low or hardly
      detectable in low-grade astrocytoma, and c-Met immunoreactivity was correlated
      with the histological grade of the tumor suggesting that the creation of HGF/SF
      autocrine loop occurs along with the progression of astrocytic brain tumors.
      Experimental evidence indicated that HGF/SF exhibits potent migration/invasion
      inducing activity for GBM cells bearing c-Met receptor. It is also a significant
      angiogenesis factor in GBM, and may serve as a cellular growth factor for certain
      GBM cells. These lines of evidence suggest that HGF/SF signaling pathway may
      serve as a promising new target of therapeutic intervention of GBM.

PMID- 10202188
TI  - Antitumor effects of interleukin-12 in pre-clinical and early clinical studies
      (Review).
AB  - Interleukin-12 (IL-12) previously called cytotoxic lymphocyte maturation factor
      (CLMF) or NK cell stimulatory factor (NKSF) is a recently characterized
      heterodimeric cytokine composed of two subunits. Although identified no more than
      10 years ago IL-12 has already proved efficacious in numerous pre-clinical tumor
      immunotherapy studies. Animal studies revealed that IL-12 has powerful antitumor,
      anti-metastatic and anti-angiogenic activities and seems to be less toxic than
      other immunotherapeutics such as interferons or IL-2. A number of pre-clinical
      studies with IL-12 prompted the evaluation of this cytokine in the treatment of
      human cancers. Results of phase I and early phase II clinical trials have already
      been reported and these are described here together with a brief discussion
      concerning IL-12-related toxicities and potential methods of their prevention.

PMID- 10202189
TI  - Morphological and morphometric studies of the splenic antitumor immune response,
      elicited by liposome-covered soluble p53 kDa antigen, in chemically-induced rat
      colon cancer.
AB  - We evaluated the splenic morphometric changes in rats treated with carcinogen to
      study development of anti-cancer immune response. When liposome-covered soluble
      53 kDa antigen (s53) was injected into these rats, significant tumor-suppression
      was seen and the percentage of tumor-free animals rose from 15.4% in non
      vaccinated rats to 53.8%. In the spleens of carcinogen treated rats that did not
      develop tumors, activity of B lymphocytes increased significantly. This was
      manifested by the expansion of the germinal centers to 50.9% of the follicular
      area reflecting depletion of B cells, and the decrease of the mantle layer to
      48.9% of the follicles. A similar picture was seen with T lymphocytes: the area
      of the marginal zone decreased to 55.2% of the T zone of the white pulp, and that
      of the periarterial lymph sheaths (PALS) to 33.6%. In tumor-bearing rats features
      of the immune decompensation were seen: the germinal centers increased to 96.5%
      of the follicular area, and the mantle layer and PALS decreased significantly.
      Vaccination prevented these effects, especially in tumor-bearing rats: the PALS
      occupies 30.4% of the white pulp and the marginal zone 56.1%, and the mantle
      layer occupied 58.1% of the follicular zone. Similar changes were found in
      vaccinated rats without tumors reflecting the compensatory character of the
      immune reaction in vaccinated rats. In conclusion, we found that treatment with
      carcinogen followed by vaccination with the s53-liposomes complex stimulated the
      activity of the splenic B, and to a lesser degree the T systems.

PMID- 10202191
TI  - Apocalyptic cardiology 

PMID- 10202190
TI  - A generation of women at risk 

PMID- 10202193
TI  - Noncritical disease of the left main coronary artery: limitations of angiography
      and the role of intravascular ultrasound.
AB  - OBJECTIVE: To review the diagnosis and management of noncritical left main stem
      disease. DATA SOURCES: MEDLINE was searched using the key phrases 'intravascular
      ultrasound' and 'left main coronary artery'. DATA EXTRACTION: Articles addressing
      the angiographic or ultrasound assessment of left main stem disease were
      systematically reviewed. Reference is also made to articles dealing with outcomes
      for patients with left main stem disease. DATA SYNTHESIS: The assessment of left
      main stem disease by coronary angiography is often suboptimal. Intravascular
      ultrasound has demonstrated significant left main stem disease in
      angiographically normal arteries. It has also demonstrated that mild to moderate
      left main stem disease frequently accompanies disease in the other coronary
      arteries. The natural history of mild to moderate left main stem disease has not
      been well characterized; thus, the optimum management of this condition is not
      known. CONCLUSIONS: To establish the natural history of noncritical left main
      stem stenosis, it is proposed that centres performing frequent intravascular
      ultrasound examinations systematically and quantitatively interrogate the left
      main stem during all left coronary examinations. Angiographic and ultrasonic
      measures of left main stem disease can then be correlated with clinical outcome
      during long term follow-up. This will clearly require the collaboration of
      several centres to generate a sufficiently large database to address these
      clinical questions.

PMID- 10202192
TI  - Underuse of acetylsalicylic acid in individuals with myocardial infarction,
      ischemic heart disease or stroke: data from the 1995 population-based Nova Scotia
      Health Survey.
AB  - OBJECTIVE: To determine current patterns of acetylsalicylic acid (ASA) use in
      Nova Scotia for individuals with self-reported myocardial infarction, stroke or
      ischemic heart disease. DESIGN: Descriptive, cross-sectional, population-based
      study using data from the 1995 Nova Scotia Health Survey (NSHS). The NSHS was
      based on a probability sample and was representative of the Nova Scotia adult
      population by age, sex and region. Survey data were obtained by standardized home
      interviews conducted by trained public health nurses. SETTING: The province of
      Nova Scotia in 1995. PARTICIPANTS: Survey respondents who reported having a
      myocardial infarction, stroke or ischemic heart disease were assessed. RESULTS:
      Among those who reported a history of myocardial infarction, stroke or ischemic
      heart disease, 55% (95% CI 47% to 63%), 49% (95% CI 38% to 61%) and 54% (95% CI
      39% to 68%), respectively, reported using ASA at the time of the survey. Overall,
      only 53% of those with cardiovascular disease were using ASA. Exclusion of
      persons with potential contraindications to ASA did not significantly increase
      these proportions. CONCLUSIONS: ASA appears to be underused in those at high risk
      for future vascular events. Further research is required to investigate
      determinants of ASA use and to increase appropriate use of ASA.

PMID- 10202194
TI  - Current status of transmyocardial laser revascularization: review of the
      literature.
AB  - BACKGROUND: Transmyocardial laser revascularization (TMLR) is a new procedure for
      the treatment of angina pectoris in which high power laser energy is used to
      create channels in ischemic myocardium. OBJECTIVE: To describe in detail the
      historical, experimental and state-of-the-art studies regarding TMLR. DATA
      SOURCES: The English-language literature published from 1966 to 1998 was
      thorougly searched in MEDLINE. Further information regarding unpublished data was
      obtained on request. STUDY SELECTION: The most important experimental studies and
      randomized prospective clinical trials were examined. Additional papers were
      selected to provide a historical perspective and future prospects of TMLR. DATA
      SYNTHESIS: Although the results of TMLR in terms of angina relief are impressive,
      the procedure is associated with significant mortality and morbidity, and the
      results of objective cardiac perfusion measurements such as radionucleic
      perfusion scans and positron emission tomography are not conclusive. Furthermore,
      little information is available concerning the effect of this procedure on life
      expectancy. This article reviews the historical background of TMLR and possible
      mechanisms by which it may work, and discusses existing evidence for and against
      the procedure and how it may be applied in the future. CONCLUSIONS: At present,
      TMLR is potentially indicated for patients with severe angina that is refractory
      to medical therapy and who have contraindications for the more traditional
      therapies (coronary artery bypass grafting, percutaneous transluminal coronary
      angioplasty and transplantation). More data are needed to evaluate fully the
      indications for this procedure.

PMID- 10202195
TI  - Cardiac neoplasms at the Canadian Reference Centre for Cancer Pathology.
AB  - OBJECTIVE: To review the Canadian Reference Centre for Cancer Pathology's
      experience with cardiac neoplasms by reviewing all cases with tumours involving
      the heart referred to the Centre from 1949 to 1995. Referred patient records,
      panel and consensus statement submissions and glass slides were reviewed in all
      cases. In selected cases additional immunohistochemical stains were obtained from
      paraffin block tissues. SETTING: National referral centre for difficult or
      interesting cancer pathology-related cases. PATIENTS: All cases were derived from
      referral of autopsy material and/or surgically resected neoplasms. Material was
      referred from 35 patients during 1949 to 1995. The group consisted of 17 males,
      17 females and one infant patient in whom the sex was not specified. The patient
      age ranged from infancy to 85 years. RESULTS: The neoplasms referred consisted of
      12 myxomas, 10 sarcomas, five lymphomas, two carcinomas, two papillary
      fibroelastomas and one each of rhabdomyoma, mesothelioma of the atrioventricular
      node, lipomatous hypertrophy of the intra-atrial septum and fibroma. The sarcomas
      were difficult to classify even with the use of additional immunohistochemical
      stains. All the lymphomas were of non-Hodgkin's type and were not of primary
      cardiac origin. CONCLUSIONS: The series of neoplasms referred to the Canadian
      Reference Centre for Cancer Pathology reflects changes in cardiac surgery,
      cardiac imaging and cardiac pathology as disciplines. Even with modern
      pathological techniques some cases, especially sarcomas, are still difficult to
      diagnose. The clinical presentation often reflects the chamber of origin of the
      neoplasm rather than being indicative of a specific tumour type.

PMID- 10202196
TI  - The contributions of Carl Ludwig to cardiology.
AB  - The basic instruments for measuring functional cardiovascular parameters and the
      most important discoveries made by Carl Ludwig and his disciples in
      cardiovascular physiology are described and put into perspective in regard to the
      further development of his methods and ideas. The most important apparatus was
      the kymograph, which, for the first time, made recording and documenting of
      functional parameters possible. This instrument was also used for the functional
      evaluation of the isolated perfused frog heart that was developed by Elias Cyon
      in Ludwig's Leipzig Physiological Institute. In the isolated frog heart,
      important phenomena were discovered such as the staircase ('Treppe'), the
      absolute refractory period and the all-or-none law of the heart. The isolated dog
      heart was used to determine the origin of the first heart sound, which was
      characterized as a muscle tone. To measure regional blood flow and eventually
      cardiac output, a flowmeter ('Stromuhr') was designed. Precise measurements of
      cardiac output became possible only when Adolf Fick had developed his principle,
      which served as the basis for the modern indicator methods. Cyon and Ludwig also
      discoverd the depressor nerve, which constitutes the basis of the baroreceptor
      reflex. Finally, the precise localization of the vasomotor centre in the
      ventrolateral medulla was achieved in Ludwig's Leipzig Physiological Institute.
      This was confirmed more than 100 years later with modern neuroanatomical methods
      making use of retrograde axonal transport. Thus, Ludwig and his scholars made
      major substantial contributions to cardiovascular knowledge that can be
      considered to constitute the basis of modern cardiology.

PMID- 10202197
TI  - Calcium channel blockers in myocardial and cerebral ischemia: a clinician's
      review from bench to bedside.
AB  - Calcium channel blockers constitute a very important group of drugs that are
      commonly used in the treatment of cardiovascular and cerebrovascular disorders.
      Current indications for these medications include hypertension, angina,
      supraventricular arrhythmias, and prevention of coronary and cerebral vasospasm.
      Although calcium channel blockers originally held great promise in the treatment
      of myocardial and cerebral ischemia, clinical results have been discouraging. An
      understanding of the basic physiological mechanisms of actions for these drugs is
      important for the practising clinician and may explain the disappointing results
      for the treatment of ischemia to date. This paper is a narrative review, from a
      clinician's viewpoint, of the structure and role of calcium channels in cardiac
      and cerebrovascular tissues, as well as a review of the in vitro and clinical
      results of calcium channel blockade in myocardial and cerebral ischemia.

PMID- 10202198
TI  - Left ventricular myxoma.
AB  - A rare development of acute inferior myocardial infarction is reported in a 23
      year-old man with no previous history of cardiovascular disease. In an
      echocardiographic study a left intraventricular tumour was diagnosed.
      Cineangiographic study showed normal coronary arteries. The tumour, a myxoma,
      originating in the ventricular septum, was resected through the left atrium after
      the anterior leaflet of the mitral valve was detached. Postoperative course was
      uneventful and the patient remained healthy 48 months after surgery.

PMID- 10202200
TI  - Current status of the irritable bowel syndrome 

PMID- 10202199
TI  - Ventricular fibrillation: an extreme presentation of primary hyperaldosteronism.
AB  - Patients with primary aldosteronism often present with hypokalemia and
      hypertension. Primary aldosteronism presenting as sudden death due to ventricular
      fibrillation is described in an otherwise healthy 37-year-old woman. After
      successful direct current cardioversion, serum potassium was 1.4 mmol/L.
      Investigations revealed a suppressed renin level, elevated serum aldosterone and
      a right adrenal nodule found on imaging. Ventricular fibrillation has not
      previously been described as a presention of a biochemically and surgically
      proven aldosterone-producing adenoma. This case highlights the importance of
      early detection and proper diagnosis of secondary hypertension before serious
      sequelae occur.

PMID- 10202201
TI  - Motor function in irritable bowel syndrome.
AB  - The evidence supporting a role of abnormal motor function in irritable bowel
      syndrome (IBS) is reviewed. Symptoms commonly present in IBS patients, such as
      vomiting, diarrhea, constipation or incomplete rectal evacuation, indicate that a
      motor disorder is implicit as either a primary or secondary disturbance.
      Physiological studies implicate a disturbance of transit through the small bowel
      and proximal colon, and abnormal motor responses of the rectum to distention in
      IBS patients. Intestinal contractions (physiological or 'abnormal') are
      associated with the sensation of pain, suggesting that these contractions are
      interactions between abnormal motor and sensory functions in IBS. Therapies aimed
      at correcting abnormal transit or antispasmodics are the main pharmacological
      approaches to the relief of IBS, and, although the latter are not always
      effective in the long term response to treatment, they support the role of
      dysmotility in IBS. Most novel therapies under trial probably modulate both
      sensory and motor functions, and are discussed briefly. In summary, the weight of
      clinical, physiological and pharmacological evidence supports a role of abnormal
      motility in IBS.

PMID- 10202202
TI  - Dimensions of gut dysfunction in irritable bowel syndrome: altered sensory
      function.
AB  - Growing evidence suggests that symptoms in patients with irritable bowel syndrome
      (IBS) may be due to a visceral sensory dysfunction. Specifically, it has been
      shown that patients with IBS have hypersensitive responses to distension of the
      rectum, whereas their tolerance to somatic stimuli is normal or even increased.
      Furthermore, patients with IBS have hypersensitivity of the small bowel, which
      selectively affects mechanosensitive afferents, with normal perception of
      electrical stimulation of the gut. Sensory dysfunctions may also be associated
      with altered reflex activity, which may contribute to the clinical symptoms.
      Normally, a series of mechanisms at different strata of the nervous system
      modulate visceral afferent input and determine conscious perception. Conceivably,
      a dysfunction of these regulatory mechanisms may alter sensitivity in clinical
      conditions. To date, neither the origin nor the clinical significance of visceral
      hyperalgesia has been elucidated. However, it seems likely that the sensory and
      reflex dysfunctions of the gut in IBS may combine to different degrees, and their
      interaction may explain the clinical pleomorphism of the syndrome.

PMID- 10202203
TI  - The autonomic nervous system in functional bowel disorders.
AB  - Communications along the brain-gut axis involve neural pathways as well as immune
      and endocrine mechanisms. The two branches of the autonomic nervous system are
      integrated anatomically and functionally with visceral sensory pathways, and are
      responsible for the homeostatic regulation of gut function. The autonomic nervous
      system is also a major mediator of the visceral response to central influences
      such as psychological stress. As defined, functional disorders comprise a
      constellation of symptoms, some of which suggest the presence of altered
      perception, while other symptoms point to disordered gastrointestinal function as
      the cause of the symptoms. A growing number of reports have demonstrated
      disordered autonomic function in subgroups of functional bowel patients. While a
      number of different methods were used to assess autonomic function, the reports
      point to a generally decreased vagal (parasympathetic) outflow or increased
      sympathetic activity in conditions usually associated with slow or decreased
      gastrointestinal motility, while other studies found either an increased
      cholinergic activity or a decreased sympathetic activity in patients with
      symptoms compatible with an increased motor activity. Under certain conditions,
      altered autonomic balance (including low vagal tone and increased sympathetic
      activity) may alter visceral perception. Autonomic dysfunction may also represent
      the physiological pathway accounting for many of the extraintestinal symptoms
      seen in irritable bowel syndrome patients and some of the frequent
      gastrointestinal complaints reported by patients with disorders such as chronic
      fatigue and fibromyalgia.

PMID- 10202204
TI  - Corticotropin-releasing factor and the brain-gut motor response to stress.
AB  - The characterization of corticotropin-releasing factor (CRF) and CRF receptors,
      and the development of specific CRF receptor antagonists selective for the
      receptor subtypes have paved the way to the understanding of the biochemical
      coding of stress-related alterations of gut motor function. Reports have
      consistently established that central administration of CRF acts in the brain to
      inhibit gastric emptying while stimulating colonic motor function through
      modulation of the vagal and sacral parasympathetic outflow in rodents. Endogenous
      CRF in the brain plays a role in mediating various forms of stressor-induced
      gastric stasis, including postoperative gastric ileus, and activates colonic
      transit and fecal excretion elicited by psychologically aversive or fearful
      stimuli. It is known that brain CRF is involved in the cross-talk between the
      immune and gastrointestinal systems because systemic or central administration of
      interleukin-1-beta delays gastric emptying while stimulating colonic motor
      activity through activation of CRF release in the brain. The paraventricular
      nucleus of the hypothalamus and the dorsal vagal complex are important sites of
      action for CRF to inhibit gastric motor function, while the paraventricular
      nucleus of the hypothalamus and the locus coeruleus complex are sites of action
      for CRF to stimulate colonic motor function. The inhibition of gastric emptying
      by CRF may be mediated by the interaction with the CRF2 receptors, while the
      anxiogenic and colonic motor responses may involve CRF1 receptors. Hypersecretion
      of CRF in the brain may contribute to the pathophysiology of stress-related
      exacerbation of irritable bowel syndrome.

PMID- 10202205
TI  - Stress-induced changes in the gastrointestinal motor system.
AB  - Several autonomic, hormonal, behavioural and neuropeptidergic bodily responses to
      stressful stimuli have been described over the past few decades. Both animal
      models and human paradigms have been explored. It is acknowledged that stress
      modulates gastrointestinal (GI) motility through central mechanisms including
      corticotropin-releasing-factor. This process requires the integrity of autonomic
      neural pathways. It has become evident that the effects of stress on GI motility
      vary according to the stressful stimulus, its intensity, the animal species under
      study and the time course of the study. Recent evidence suggests that chronic or
      possibly permanent changes develop in enteric smooth muscle properties in
      response to stress. In animals, the most consistent findings include retardation
      of gastric emptying in response to various stressors; acceleration of gastric
      emptying upon cold stress, presumably through the secretion of brain
      thyroglobulin-hormone; acceleration of intestinal transit; and stimulation of
      colonic transit and fecal output. In humans, the cold water immersion test has
      been associated with an inhibition of gastric emptying, while labyrinthine
      stimulation induces the transition from postprandial to fasting motor patterns in
      the stomach and the small bowel. Psychological stress has been shown to induce a
      reduction in the number and amplitude of intestinal migrating motor complexes and
      to neither affect nor stimulate colonic motility. These various responses to
      stress are presumably attributed to the preferential activation of specific
      neuronal pathways under the influence of a given stimulus or its intensity. The
      significance of these findings and the directions of further studies are
      discussed.

PMID- 10202206
TI  - Stress and visceral perception.
AB  - Functional bowel disorders are characterized by the presence of a visceral
      hyperalgesia in most patients. This visceral hyperalgesia is related to an
      enhanced perception of sensations originating from the gut. Stressful events can
      dramatically influence the course of functional bowel disorders, and patients
      suffering from these syndromes appear to be more susceptible to the stressful
      events of daily life. However, until now, few studies have evaluated the
      relationship between stress and visceral perception. Some studies of healthy
      volunteers indicated contradictory results, but the studies used different
      methodologies. During stress conditions, either physical or mental, thresholds of
      perception of rectal distension were increased, suggesting a 'distraction
      effect', or were decreased, supporting a sensitizing effect of stress. In most
      studies, rectal compliance was not affected, but stress has been shown to alter
      the rectal tone, as measured by a barostat. One study comparing irritable bowel
      syndrome patients with controls demonstrated the importance of cognitive
      processes in the modulation of visceral perception by stress. Animal studies have
      also demonstrated the sensitizing effect of stress on the perception of rectal
      distension. Mediators involved may be numerous, but corticotropin-releasing
      factor has been demonstrated to play a major role at the central level. Mast
      cells and histamine release may play a role at the peripheral level. Stress can
      thus be included in an integrative model explaining the pathophysiology of
      functional bowel disorders. Advances in the understanding of the relationship
      between stress and visceral perception may constitute a basis for a therapeutic
      approach of functional bowel disorders targeted on the central nervous system.

PMID- 10202207
TI  - Peripheral contributions to visceral hyperalgesia.
AB  - Hyperalgesia has long been recognized clinically as a consequence of tissue
      injury. Primary hyperalgesia (arising from the site of injury) is generally
      considered to be due to sensitization of sensory receptors (eg, nociceptors) and
      perhaps activation of so-called 'silent nociceptors' by mediators released,
      synthesized or attracted to the site of tissue injury. Key questions associated
      with understanding visceral hyperalgesia relate to whether the viscera are
      innervated by nociceptors (ie, sensory receptors that respond selectively to
      noxious intensities of stimulation), whether visceral receptors and/or afferent
      fibres sensitize after tissue injury and whether silent nociceptors exist in the
      viscera. Studies in nonhuman animals have revealed that hollow organs such as the
      esophagus, gall bladder, stomach, urinary bladder, colon and uterus are
      innervated by mechanically sensitive receptors with low or high thresholds for
      response. Accordingly, it appears that the viscera are innervated by nociceptors,
      although the issue is far from settled. One characteristic of cutaneous
      nociceptors is their ability to be sensitized when tissue is injured.
      Mechanosensitive visceral receptors also sensitize when the viscera are
      experimentally inflamed, but both visceral receptors with low thresholds and
      those with high thresholds for response are sensitized. Moreover, it is often not
      appreciated that visceral receptors are likely polymodal rather than unimodal -
      that is, mechanically sensitive visceral receptors typically are also sensitive
      to chemical and/or thermal stimuli. In this sense, visceral receptors may be
      considered evolutionarily older than more highly developed, specialized cutaneous
      receptors. Finally, there are mechanically insensitive receptors that innervate
      the viscera and, when tissue is injured, develop spontaneous activity and acquire
      sensitivity to mechanical stimuli. In the aggregrate, visceral receptors change
      their behaviour in the presence of tissue injury and, along with activated
      mechanically insensitive receptors, increase the afferent barrage into the spinal
      cord, contributing to the development of visceral hyperalgesia.

PMID- 10202208
TI  - Effects of inflammatory mediators on gut sensitivity.
AB  - Over the past decade, attention has been paid to the role of visceral sensitivity
      in the pathophysiology of functional bowel disorders, especially irritable bowel
      syndrome, and visceral hypersensitivity is the most widely accepted mechanism
      responsible for both motor alterations and abdominal pain. Inflammatory mediators
      sensitize primary afferents, especially C-fibre polymodal nociceptors, favouring
      the recruitment of silent nociceptors that give rise to secondary spinal
      sensitization. After local tissue injury, the release of chemical mediators such
      as potassium ions, ATP, bradykinin and prostaglandin E2 directly activate nerve
      endings and indirectly trigger the release of algesic mediators such as
      histamine, 5-hydroxytryptamine and nerve growth factor from other cells, which,
      in turn, stimulate proximal afferent nerve endings and silent nociceptors. Among
      the intermediary structures activated by inflammatory mediators and susceptible
      to the release of proalgesic substances, mast cells and platelets play a crucial
      role; however, immunocytes such as macrophages and neutrophils or sympathetic
      nerve terminals are also candidates. Moreover, events likely to activate
      synthesis of mediators by mast cells, such as stress and septic shock, also
      trigger colonic hypersensitivity. Prolonged visceral hyperalgesia may also depend
      on spinal sensitization. A number of substances are candidates to play a role at
      the spinal cord level in mediating painful and nonpainful sensations. Among them,
      substance P, dynorphins and glutamate play a pivotal role in postsynaptic
      sensitization, particularly during and after gut inflammation. Finally, despite
      the complexity of the relationship between inflammatory mediators and gut
      hypersensitivity, numerous results strongly suggest that alteration neuroimmune
      communications at the gut level may trigger a series of events that give rise to
      chronic changes in visceral sensitivity.

PMID- 10202209
TI  - Stress, inflammation and the irritable bowel syndrome.
AB  - Studies in animals have shown that inflammation of the mucosa of the
      gastrointestinal tract is accompanied by changes in enteric nerve and smooth
      muscle function, and in gut motility and sensation. In some instances, these
      changes persist long after resolution of the mucosal inflammation. Some of these
      observations have been made in human studies of irritable bowel syndrome (IBS) in
      patients after an enteric infection or in patients in remission from ulcerative
      colitis. Stress has also been implicated as a modulator of gastrointestinal
      inflammation in both animal and human studies. In animals, stress causes a
      reactivation of previous enteric inflammation and induces the attendant
      physiological changes. Prior stress also enhances the response to subsequent
      inflammatory stimuli. In humans, postinfectious IBS tends to occur in patients
      with psychological profiles similar to those observed in IBS patients and in whom
      there is a higher incidence of stressful life events just before exposure to the
      infection. Taken together, these observations link stress and inflammation as a
      putative pathogenetic mechanism in at least a subset of IBS patients.

PMID- 10202211
TI  - Approaches to the modulation of abdominal pain.
AB  - Despite their high prevalence and significant economic impact on the health care
      system, functional gastrointestinal disorders have evaded successful therapy.
      Conventional medical therapies are based on inadequate disease models, and the
      great majority of published treatment trials are flawed in their design,
      permitting no conclusions to be drawn about the true efficacy of any particular
      treatment. During the past several years, a new, comprehensive disease model
      based on alterations in brain-gut interactions has rapidly evolved. Even though
      the precise mechanisms and sites underlying these alterations remain incompletely
      understood, plausible targets for the development of effective pharmacological
      treatments are receptors on peripheral terminals of visceral afferent nerves
      (opioids and serotonin), ion channels and receptors on dorsal horn neurons within
      the spinal cord (opioids, glutamate, calcitonin gene-related peptide and
      neurokinin-1), and supraspinal targets in the brainstem within the limbic system
      and in the prefrontal cortex (serotonin, catecholamines, dopamine and
      acetylcholine). Regardless of the primary pathophysiology underlying functional
      gastrointestinal disorders (ie, central versus peripheral), different
      pharmacological strategies targeted at different sites in the periphery or within
      the central nervous system may become effective therapies in the future.

PMID- 10202210
TI  - Management of irritable bowel syndrome: novel approaches to the pharmacology of
      gut motility.
AB  - Although it is unclear to what extent irritable bowel syndrome (IBS) symptoms
      represent a normal perception of abnormal function or an abnormal perception of
      normal function, many believe that IBS constitutes the clinical expression of an
      underlying motility disorder, affecting primarily the mid- and lower gut. Indeed,
      transit and contractile abnormalities have been demonstrated with sophisticated
      techniques in a subset of patients with IBS. As a consequence, drugs affecting
      gastrointestinal (GI) motility have been widely employed with the aim of
      correcting the major IBS manifestations, ie, pain and altered bowel function.
      Unfortunately, no single drug has proven to be effective in treating IBS symptom
      complex. In addition, the use of some medications has often been associated with
      unpleasant side effects. Therefore, the search for a truly effective and safe
      drug to control motility disturbances in IBS continues. Several classes of drugs
      look promising and are under evaluation. Among the motor-inhibiting drugs, gut
      selective muscarinic antagonists (such as zamifenacin and darifenacin),
      neurokinin2 antagonists (such as MEN-10627 and MEN-11420), beta3-adrenoreceptor
      agonists (eg, SR-58611A) and GI-selective calcium channel blockers (eg,
      pinaverium bromide and octylonium) are able to decrease painful contractile
      activity in the gut (antispasmodic effect), without significantly affecting other
      body functions. Novel mechanisms to stimulate GI motility and transit include
      blockade of cholecystokinin (CCK)A receptors and stimulation of motilin
      receptors. Loxiglumide (and its dextroisomer, dexloxiglumide) is the only CCKA
      receptor antagonist that is being evaluated clinically. This drug accelerates
      gastric emptying and colonic transit, thereby increasing the number of bowel
      movements in patients with chronic constipation. It is also able to reduce
      visceral perception. Erythromycin and related 14-member macrolide compounds
      inhibit the binding of motilin to its receptors on GI smooth muscle and,
      therefore, act as motilin agonists. This antibiotic accelerates gastric emptying
      and shortens orocecal transit time. In the large bowel a significant decrease in
      transit is observed only in the right colon, which suggests a shift in fecal
      distribution. Several 'motilinomimetics' have been synthesized. Their development
      depends on the lack of antimicrobial activity and the absence of fading of the
      prokinetic effect during prolonged administration. 5-hydroxytryptamine (5-HT)4
      agonists with significant pharmacological effects on the mid- and distal gut
      (such as prucalopride and tegaserod) are available for human use. These
      'enterokinetic' compounds are useful for treating constipation-predominant IBS
      patients. 5-HT3 receptor antagonists also possess a number of interesting
      pharmacological properties that may make them suitable for treatment of IBS.
      Besides decreasing colonic sensitivity to distension, these drugs prolong
      intestinal transit and may be particularly useful in diarrhea-predominant IBS.
      Finally, when administered in small pulsed doses, octreotide, besides reducing
      the perception of rectal distension, accelerates intestinal transit, although
      other evidence disputes such an effect.

PMID- 10202213
TI  - Acquired motility disorders in childhood.
AB  - Acquired motility disorders in childhood cause a number of gastrointestinal
      symptoms - principally, recurrent vomiting, abdominal pain and distension,
      constipation and loose stools. Gastrointestinal motility disorders result from
      disturbances of the control mechanisms of gut motor activity, which may be
      produced by organic disease involving enteric nerves and muscle, perturbation of
      the humoral environment of the nerves and muscle, and altered central nervous
      system input. In children, both congenital and acquired disease processes may
      produce these pathogenetic mechanisms, resulting in syndromes that vary in
      severity from chronic intestinal pseudo-obstruction to the irritable bowel
      syndrome.

PMID- 10202214
TI  - A European approach to irritable bowel syndrome management.
AB  - Irritable bowel syndrome (IBS) is characterized by a number of clinical features
      and probably comprises a cluster of different conditions. The most frequent
      symptom reported by IBS patients is abdominal pain, although for a number of
      patients, bowel disturbances are the most prominent symptoms. Diarrhetic patients
      are seen in referral centres in continental Europe less frequently than in the
      United Kingdom or the United States. On the contrary, patients with constipation
      prone IBS may comprise up to 80% of the IBS population referred to these centres.
      The pathophysiology of IBS is based on multiple factors. Most of the therapeutics
      proposed for the management of patients with IBS have been developed on the
      assumption that motility disorders of the gut are the most reliable pathological
      findings among these patients. Consequently, antispasmodics and motility
      regulatory agents have been widely used, alone or in association with intestinal
      adsorbents (clay-derived preparations), and laxatives or antidiarrhetic agents.
      Most of these drugs were developed several decades ago, and studies showing their
      efficacy have not reached the level of quality that is now required of randomized
      controlled trials. Therefore, following a complete and detailed review published
      in 1989, these drugs have not been used extensively in the United Kingdom or the
      United States. Large inquiries have also shown that the duration of prescription
      is quite different among countries. In European countries, maintenance therapy is
      frequently prescribed for several weeks to attempt to decrease the number of
      acute episodes. In contrast, psychotropic drugs are less popular among European
      gastroenterologists than among American gastroenterologists. However,
      multidisciplinary approaches to the treatment of these patients are frequent, and
      such drugs are often prescribed by home physicians. The results of large surveys
      estimated the yearly cost of such treatments to be around US$850. Patients with
      constipation and elderly patients with chronic disease receive more expensive
      treatments.

PMID- 10202212
TI  - Role of opioid ligands in the irritable bowel syndrome.
AB  - Endogenous opioid peptides - enkephalins, beta-endorphin and dynorphins - are
      located in specific sites of the brain, the spinal cord, the autonomic ganglia
      and the enteric nervous system. Endogenous opioids participate in the regulation
      of nervous visceral afference and sensitivity as well as of several visceral
      motor function induced by the central nervous system and through the
      enteroenteric and the myoenteric reflexes. Their final effect on gut physiology
      is the net and harmonically balanced result of their binding to mu, delta and
      kappa opioid receptor subtypes. Exogenous opioid receptor ligands with different
      affinities for the opioid receptor subtypes have been effectively used to modify
      and normalize altered gut functions. The mu receptor agonists - morphine and, to
      a greater extent, the meperidine congeners diphenoxylate and loperamide - have
      been shown to slow gastrointestinal transit by their effects on the circular and
      longitudinal muscle of the intestine. Diphenoxylate and, more efficiently,
      loperamide, for the lack of any effect on the central nervous system, have been
      usefully employed in the treatment of diarrhea in irritable bowel syndrome (IBS)
      patients. Unlike the mu receptor agonists morphine and loperamide, which
      invariably stimulate colonic motility, trimebutine, which has almost equal
      affinity for mu, delta and kappa receptors, has no effect on normal colonic
      activity but reduces the abnormal increase in postprandial motor activity in IBS
      patients and accelerates slow large bowel transit in constipated patients. Opioid
      ligands can be usefully employed to normalize altered visceral sensitivity in IBS
      patients. The kappa receptor agonist fedotozine exerts its antinociceptive effect
      by acting on peripheral nerve endings of sensory vagal and nonvagal afferent
      pathways. Fedotozine has been shown to increase the threshold of perception to
      colonic distension in experimental conditions and to affect favourably symptoms
      of IBS in clinical trials.

PMID- 10202215
TI  - The economic burden of irritable bowel syndrome in Canada.
AB  - In the treatment of irritable bowel syndrome (IBS), medical practitioners and
      policymakers face the task of providing both high quality and cost effective
      medical care for a condition with no certain cure. To date, studies have examined
      only total medical costs to patients with symptoms consistent with an IBS
      diagnosis. However, these studies have not examined the direct and indirect costs
      incurred in the course of treatment for IBS, excluding the costs of unrelated
      medical conditions. Because patients with IBS have been shown to differ
      significantly from non-IBS patients in their desire to seek medical care, one
      cannot consider solely the cost differential in medical costs for IBS and non-IBS
      patients. The present study examines a set of patients who have been diagnosed
      with IBS and seek medical care for IBS.

PMID- 10202216
TI  - "You are old, Father William...".

PMID- 10202217
TI  - Unilateral lung volume reduction before pneumonectomy: a brief comment.

PMID- 10202218
TI  - Lung volume reduction for emphysema and the Canadian Lung Volume Reduction
      Surgery (CLVR) Project.
AB  - OBJECTIVE: To review the literature on the surgical treatment of emphysema and to
      present preliminary results from a pilot study of lung volume reduction (LVR)
      surgery. DESIGN: Case series of consecutive patients referred for LVR surgery.
      Outcomes were quality of life, pulmonary function and exercise capacity. SETTING:
      Two university-affiliated hospitals in Ontario. POPULATION STUDIED: Patients
      between the ages of 40 and 75 years with emphysema who had severe airflow
      limitation, hyperinflation of the lungs and impaired quality of life.
      INTERVENTION: Bilateral reductions with multiple wedge resections of the lung
      using a linear stapling device with bovine pericardial buttressing were completed
      via a median sternotomy. MAIN RESULTS: Of 50 patients referred, 24 underwent LVR
      surgery. Mean age of the cohort was 63 years. Operative 30-day or in hospital
      mortality was 8%. Two other patients (8%) died from respiratory failure after LVR
      within the first year. Postoperative complications included prolonged air leaks
      (six of 24), tracheobronchitis (five of 24), mechanical ventilation (four of 24)
      and pneumonia (three of 24). Mean length of stay was 18 days (median 12 days). At
      one year, there was a sustained decrease in total lung capacity from 133% to 123%
      predicted. There were improvements in forced expiratory volume in 1 s, from 22%
      of predicted preoperatively to 32% postoperatively, and in 6 min walk
      performance, from 345 to 381 m. Improvements were also noted in the quality of
      life assessments. CONCLUSIONS: Preliminary results suggest that LVR surgery is
      feasible and may improve the patient's quality of life, pulmonary function and
      exercise capacity. A randomized clinical trial comparing LVR plus the best
      medical management with the best medical management alone is currently underway
      to determine the effectiveness of LVR.

PMID- 10202219
TI  - PCR detection of viral nucleic acid in fatal asthma: is the lower respiratory
      tract a reservoir for common viruses?
AB  - BACKGROUND: There is indirect evidence implicating viral respiratory tract
      infections in the pathogenesis of fatal asthma. However, it is unknown whether
      viruses are present within the lower respiratory tract in fatal asthma.
      OBJECTIVES: To apply a nine-virus polymerase chain reaction (PCR) panel to
      postmortem specimens of lower airway secretions and compare the prevalence of
      viral nucleic acid among patients who died of asthma, asthmatic patients who died
      of other causes and persons who died without lung disease. PATIENTS AND METHODS:
      Postmortem specimens of lower airway secretions from patients who died of asthma
      (fatal asthma [n=10]), asthmatic patients who died of other causes (n=4) and
      nonasthma controls (n=6) underwent PCR for nine common respiratory viruses. The
      prevalence of each virus was compared among the three groups. RESULTS: PCR was
      positive for at least one virus in 19 of 20 cases, and multiple viruses were
      detected in 14 of 20 cases. The prevalence of each virus was similar in the three
      groups studied. CONCLUSIONS: In fatal asthma, lower airway secretions do not show
      a specific pattern of viral nucleic acid. Intriguingly, these results suggest
      that the lower respiratory tract may act as a potential reservoir for common
      respiratory viruses.

PMID- 10202221
TI  - Pulmonary rehabilitation programs in Canada: national survey.
AB  - OBJECTIVE: To characterize pulmonary rehabilitation (PR) programs in terms of
      their type, size, duration, patient population, content and staffing. DESIGN:
      Surveys were sent to members of the Rehabilitation Committee of the Canadian
      Thoracic Society, as well as any program identified by members of the Canadian
      Physiotherapy Cardio-Respiratory Society, by provincial lung associations or by
      the respondents. PARTICIPANTS: Of 51 surveys sent, responses were received from
      44 facilities (86% response rate). In-patient or out-patient pulmonary
      rehabilitation programs were offered by 36 facilities. RESULTS: Most programs
      (97%) admitted out-patients, and 22% had an in-patient capability. Out-patient
      programs enrolled 13 patients (median 11; range five to 48) at a given time for a
      duration of 8.3 weeks (range two to 26). In-patient programs enrolled nine
      patients at a given time (range two to 26) for 4.6 weeks (range one to eight).
      Programs included patients with chronic obstructive pulmonary disorder (100%),
      restrictive disease (93%), asthma (82%), adults with cystic fibrosis (46%),
      patients pre- or postlung transplantation (45%) and patients receiving mechanical
      ventilatory support (18%). Breathing retraining, education and upper extremity
      training were incorporated in more than 90% of all programs. Only one-third of
      programs offered smoking cessation as part of the rehabilitation. Education
      sessions on medications and inhaler usage were included in most programs, but
      sexuality was addressed in only half the programs. CONCLUSIONS: This first
      comprehensive national survey of PR programs in Canada shows that there are
      similarities in the format, content and staffing of PR programs. Programs are
      only able to service a small percentage of patients with chronic respiratory
      conditions.

PMID- 10202220
TI  - Salmeterol and fluticasone propionate (50/250 microg) administered via
      combination Diskus inhaler: as effective as when given via separate Diskus
      inhalers.
AB  - OBJECTIVE: To compare the efficacy and safety of a new combination Diskus inhaler
      containing both salmeterol 50 mg and fluticasone propionate 250 mg (Seretide)
      with the two drugs delivered via separate Diskus inhalers. DESIGN: A multicentre,
      double-blind, double-dummy study. Three hundred and seventy-one symptomatic
      asthma patients (age range 13 to 75 years, mean 42 years) receiving inhaled
      corticosteroids were randomly assigned to two treatment groups: 28 weeks'
      treatment with either salmeterol/fluticasone propionate (50/250 microg bid) via a
      single Diskus inhaler (combination) and placebo bid via another Diskus inhaler,
      or salmeterol 50 microg bid via one Diskus inhaler and fluticasone propionate 250
      microg bid via another (concurrent). Morning peak expiratory flow rate (PEFR) and
      symptoms were measured for the first 12 weeks and safety data were collected
      throughout the study. RESULTS: Over weeks 1 to 12, adjusted mean improvements in
      morning PEFR were 43 and 36 L/min for combination and concurrent therapies,
      respectively. The difference between the two treatment arms was 6 L/min (90% CI 
      13 to 0 L/min; P=0.114), which was within the predefined criteria for clinical
      equivalence. Adjusted mean improvements in forced expiratory volume in 1 s from
      baseline for week 28 were also similar between the two therapies. Thirty-five per
      cent of patients receiving combination inhaler and 31% of those receiving
      concurrent therapy had a mean daytime symptom score of zero over weeks 1 to 12
      compared with 1% and 2%, respectively, at baseline. There was no difference in
      the incidence of adverse events between the two treatment arms. Mean serum
      cortisol levels were similar, and no differences in frequency of abnormal results
      were noted between the two groups. CONCLUSIONS: This study shows that the
      combination of salmeterol and fluticasone propionate in a single inhaler is as
      efficacious in achieving asthma control and as well tolerated over a 28-week
      period as the two drugs administered individually.

PMID- 10202223
TI  - Determinants of risk factors for asthma.
AB  - There are a number of risk factors for the development of asthma, including
      genetic and environmental components. Moreover, there is mounting evidence that a
      variety of genes are associated with the features of asthma, such as persistent
      wheezing, airway responsiveness and chronic bronchial inflammation. However, for
      expression of these features, other factors must also come into play. This paper
      focuses on the importance of environmental factors in the development of asthma,
      including allergens and respiratory infections. From current evidence, it appears
      that in subjects with the appropriate genetic make-up, infections and allergens
      induce a proinflammatory cytokine response that causes airway inflammation and
      that in turn leads to the initiation and persistence of altered airway function.

PMID- 10202222
TI  - Acute respiratory distress syndrome: 30 years later.
AB  - Acute respiratory distress syndrome (ARDS) was first described about 30 years
      ago. Modern definitions and statements have recently been proposed to describe
      ARDS accurately, but none is perfect. Diffuse alveolar damage is the basic
      pathological pattern most commonly observed in ARDS, and the term includes
      permeability edema. The alveolar epithelium of the alveolar-capillary barrier is
      clearly a key component requiring repair, given its multipotent functional
      activity. Lung inflammation and neutrophil accumulation are essential markers of
      disease in ARDS, and a wide variety of pro- and anti-inflammatory cytokines have
      been described in the alveolar fluid and blood of patients. These molecules still
      have to prove their value as diagnostic or prognostic biomarkers of ARDS.
      Supportive therapy in ARDS improved in the past decade; mechanical ventilation
      with lung protective strategies and patient positioning are gaining interest, but
      the indications for corticosteroids for ARDS are still debated. Nitric oxide may
      have a place in the treatment of one-third of patients. Novel approaches, such as
      surfactant replacement and liquid ventilation, may further improve supportive
      therapy. Innovative interventions may be on the horizon in treatments that help
      to resolve or modulate common pathways of ARDS, such as inflammation (eg,
      granulocyte-colony stimulating factor) or epithelial repair (eg, keratinocyte
      growth factor).

PMID- 10202225
TI  - Risks and outcomes in community acquired pneumonia.
AB  - Risks and probable outcomes in patients with community acquired pneumonia have
      always been assessed intuitively by clinicians, but are now being intensively and
      formally studied. Several risk scoring systems have been developed to assign
      patients to different risk categories, with respect to important outcomes such as
      mortality or intensive care unit admission. Predictive factors include
      demographic characteristics such as age and sex, comorbidities such as neoplastic
      disease or congestive heart failure, abnormalities on physical examination and
      abnormal laboratory findings. Prospective use of one such prediction rule found a
      mortality rate of 0.5% in the lowest risk category, rising to 27.1% in the
      highest risk group. Formal assessment of risk can assist the clinician in
      deciding whether to treat a patient at home or in hospital, and can be an
      important step in developing clinical practice guidelines.

PMID- 10202224
TI  - Unilateral lung volume reduction in preparation for contralateral pneumonectomy.
AB  - A case of staged trans-sternal unilateral lung volume reduction (LVR) on the
      right followed by contralateral pneumonectomy for a locally advanced left lung
      malignancy is presented. The predicted symptomatic and functional benefit offered
      by LVR was felt to be necessary before the removal of the left lung. The patient,
      a 50-year-old male, with a history of chronic air flow limitation secondary to
      bullous emphysema, underwent a left pneumonectomy six weeks following a right LVR
      procedure for poor pulmonary function secondary to generalized emphysema. On
      admission, forced expiratory volume in 1 s (FEV1) was 1.37 L, 47% of predicted
      with an FEV1/forced vital capacity of 56%. Five weeks after the unilateral LVR,
      the patient's FEV1 was 1.85 L, and one year postdischarge from hospital, FEV1 was
      0.9 L. One year after discharge, the patient did not require oxygen support, and
      was active and free of malignant disease.

PMID- 10202226
TI  - Emergency department management of pneumonia.
AB  - Many patients with pneumonia, especially those who are more severely ill, have
      their first medical contact in the emergency department. Pneumonia is usually
      diagnosed with appropriate signs and symptoms, although these can be lacking in
      the very young or the old. Gram stain and culture are seldom useful. The choice
      of appropriate antibiotic is usually determined by degree of illness and
      microbiological epidemiology. The most important decision made in the emergency
      department is whether to admit the patient with pneumonia to hospital; this
      decision can be aided by the use of clinical predictive rules. Initial treatment
      of pneumonia includes supportive care as needed (oxygen, intubation and
      bronchodilators) and an empirically chosen antibiotic. Appropriate choices
      include macrolides and azalides for low risk out-patients, and either a
      combination cephalosporin and macrolide or an extended spectrum fluoroquinolone
      in anticipation of drug-resistant Streptococcus pneumoniae for high risk out
      patients and in-patients.

PMID- 10202227
TI  - Role of 'atypical' pneumonia pathogens in respiratory tract infections.
AB  - The 'atypical' pathogens are important causes of pneumonia, causing illness
      ranging from mild to life-threatening. The most common atypical pathogens are
      Mycoplasma pneumoniae and Chlamydia pneumoniae; others include Legionella
      species, Chlamydia psittaci and viruses such as influenza, adenovirus and
      respiratory syncytial virus. Infection rates for these agents are difficult to
      determine because many clinicians and investigators do not routinely test for
      them, but reported rates are in the range of up to 8% (for C pneumoniae) and 15%
      to 20% (M pneumoniae) of all cases of pneumonia. Diagnostic testing is very
      difficult because most of these agents cannot be easily cultured. Diagnosis
      relies on either high acute antibody titres (quickly available but not very
      accurate) or paired serology samples (more accurate but requires at least a
      week). While rapid identification using automated polymerase chain reaction
      testing may be possible in the future, current management is based largely on
      empirical treatment.

PMID- 10202228
TI  - A review of the mechanisms of action and resistance of antimicrobial agents.
AB  - Over the past 60 years, the introduction of new antibiotics has been matched by
      the development of new mechanisms of resistance by the bacteria. Current
      antibiotics act at a variety of sites within the target bacteria, including the
      cross-linking enzymes in the cell wall (beta-lactams), various ribosomal enzymes
      (macrolides, tetracyclines and aminoglycosides), nucleic acid polymerases
      (quinolones and rifampin) and folate synthesis (sulphas and trimethoprim). Four
      major mechanisms of resistance have been shown. Target site alterations, such as
      changes to the penicillin-binding protein, are common. Inactivation of
      antimicrobials, as by penicillinases or the new carbapenemases, is often seen.
      Some bacteria such as Pseudomonas aeruginosa can produce alterations in cell wall
      permeability that deny access to antimicrobials during the course of therapy.
      Finally, newly described efflux mechanisms pump the antimicrobial out of the cell
      before it can reach its target site.

PMID- 10202229
TI  - Clinical implications of resistance in the management of respiratory tract
      infections.
AB  - Antibiotic resistance among the three major respiratory pathogens (Streptococcus
      pneumoniae, Haemophilus influenzae and Moraxella catarrhalis) has increased
      dramatically over the past 15 years, around the world. With S pneumoniae,
      penicillin resistance is reported in almost a quarter of isolates, with multiple
      resistance an increasing problem. The major concern with H influenzae is
      ampicillin resistance, mediated through two different mechanisms. In the case of
      M catarrhalis, beta-lactamase production is almost universal, although resistance
      to other antibiotics is rare. The increasing prevalence of resistance underscores
      the need for new effective antibiotics. The new quinolones have a spectrum of
      activity that parallels the range of common respiratory pathogens.

PMID- 10202230
TI  - Evolving patterns of resistance to respiratory pathogens in Canada.
AB  - Active surveillance of changing resistance patterns is difficult but important
      for rational therapeutic choices. In Canada, penicillin resistance in
      Streptococcus pneumoniae has evolved more slowly than in other countries (in
      Europe and Israel rates exceed 50%). Currently, penicillin resistance is found in
      roughly 21% of Canadian isolates, and cross-resistance is becoming common. Beta
      lactamase production is now found in approximately 28% of Haemophilus influenzae
      isolates, although more recently, rates over 30% have been found in some areas of
      Canada. In Moraxella catarrhalis, beta-lactamases are produced by 80% to 90% of
      bacteria, with resistance to trimethoprim/sulphamethoxazole also found. To date,
      there have been only a few reports of resistance to the fluoroquinolones. The
      apparent increase in the rate of development of resistance and cross-resistance
      will lead to new therapeutic challenges.

PMID- 10202231
TI  - How should we evaluate new anti-infectives for respiratory tract infections?
AB  - In assessing the outcomes of anti-infective therapy, microbiological and clinical
      efficacy have been the most important factors considered. However, increasing
      attention is being paid to pharmacoeconomic considerations, which include much
      more than simply the cost of the drug. Nursing and pharmacy time involved in drug
      preparation and administration, laboratory costs and time in therapeutic drug
      monitoring, and hospital costs for in-patient care are all factors to be
      considered. Therapeutic failure caused by using an inexpensive but ineffective
      drug can thus be very expensive if it leads to prolonged hospitalization. The
      effort to curb anti-infective drug costs has led to the following strategies:
      sequential therapy using equipotent oral formulations of intravenous agents;
      switch therapy, ie, changing to a different class; and step-down therapy, ie,
      converting to an oral antimicrobial with less potency. Maximal cost effectiveness
      is related to rapid and effective therapy.

PMID- 10202232
TI  - Levofloxacin in the treatment of community acquired pneumonia.
AB  - Levofloxacin is the first fluoroquinolone with enhanced activity against
      Streptococcus pneumoniae to be released in Canada. In vitro, it is active against
      more than 99% of isolates of S pneumoniae, even those resistant to penicillin. It
      is also active against respiratory pathogens such as Haemophilus influenzae,
      Moraxella catarrhalis, Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella
      species. When given orally, bioavailability is greater than 99%, and the drug is
      highly concentrated in lung tissue and macrophages. Drug levels are compatible
      with once-daily dosing. In a large clinical trial, levofloxacin has shown
      clinical and microbiological superiority compared with ceftriaxone/cefuroxime.
      The characteristics of levofloxacin - high oral bioavailability, long duration of
      effect, activity against key respiratory pathogens and high tolerability -
      suggest that it will be a useful drug in the treatment of community acquired
      pneumonia.

PMID- 10202233
TI  - Management of acute exacerbation of chronic bronchitis.
AB  - In chronic bronchitis, a common respiratory illness marked by chronic productive
      cough and caused largely by cigarette smoking, bacterial exacerbations are
      thought to be a common cause of progressive airway damage. Common bacterial
      pathogens, found in 50% to 60% of episodes, include Haemophilus influenzae (the
      most common), as well as Haemophilus parainfluenzae, Streptococcus pneumoniae and
      Moraxella catarrhalis. Bacterial resistance to antibiotics, especially beta
      lactam drugs such as amoxicillin, is increasingly common in these pathogens. In
      this illness, clinical risk stratification based on age, history and comorbidity
      is an important strategy. Patients in the lowest risk group likely have viral
      infections and require no specific treatment. Patients in the higher risk groups
      require aggressive treatment to avoid treatment failure, which can lead to
      prolonged hospitalization and complications. Preventive therapies (smoking
      cessation and influenza vaccination) are worthwhile measures for these patients.

PMID- 10202234
TI  - Acute community acquired bacterial sinusitis: To treat or not to treat.
AB  - The paranasal sinuses, normally sterile, are prone to bacterial invasion as a
      complication of viral illnesses such as the common cold. Using computed
      tomograms, abnormalities of the sinuses can be seen in 90% of healthy adults with
      upper respiratory tract infections; only 2% of these patients will develop
      bacterial sinusitis. Possible rationales for antibiotic treatment of sinusitis
      include the normal sterility of the sinuses, the clinical morbidity associated
      with sinusitis, the possibility of serious intracranial and periorbital
      complications in untreated cases, and the possible progression of acute
      infections to chronic sinus disease. Evidence from the literature supports
      antibiotic treatment of sinusitis to eradicate infection and to reduce symptoms.
      There is insufficient literature evidence to prove that antibiotic treatment
      reduces serious complications or reduces progression to chronic sinus disease.
      Treatment should include an antimicrobial with a spectrum likely to cover the
      important pathogens, including those with high levels of resistance.

PMID- 10202235
TI  - Otitis media: To treat or not to treat?
AB  - Acute otitis media affects at least 80% of children younger than two years of age
      and is responsible for a third of physician visits of children younger than five
      years of age. Diagnosis must be based on more than an injected tympanic membrane;
      systemic signs and symptoms such as fever, irritability and reduced appetite are
      important, as is reduced mobility of the ear drum assessed with pneumatic
      otoscopy or impedance tympanometry. Once otitis media has been accurately
      diagnosed, treatment with antibiotics appears to improve outcomes and to reduce
      complications, such as mastoiditis, although results from different studies
      conflict.

PMID- 10202236
TI  - New strategies for allogeneic bone marrow transplantation and organ allografts.
AB  - In humans, the success rate of bone marrow transplantation (BMT) across major
      histocompatibility complex (MHC) barriers is not high due to: (1) graft-versus
      host reaction (GvHR); (2) graft rejection, and (3) incomplete T cell recovery. In
      mice, GvHR can be prevented if T cell- depleted bone marrow cells (BMCs; <2% T
      cells) are used. Graft rejection can be prevented by either bone grafts (to
      recruit donor-derived stromal cells) or the injection of donor BMCs via the
      portal vein (p.v; to induce donor-specific tolerance). T cell functions are
      recovered by BMT plus bone grafts if the thymic functions of recipients are not
      completely lost. After the complete loss of thymic functions (due to aging), BMT
      plus embryonal thymus grafts should be carried out.Recently, we have found that
      persistent donor-specific tolerance can be induced if allogeneic hemopoietic stem
      cells are injected via the p.v. Based on these findings, we have established new
      strategies for organ allografts. Without irradiation, donor BMCs should be
      injected from the p.v. injection on day 0 plus i.v. injection on day 5, and an
      immunosuppressant (CsA or FK506) should be used on days 2 and 5. Without using
      immunosuppressants, sublethal irradiation (7 Gy) followed by skin allografts plus
      allogeneic BMC injection via the p.v. should be carried out. This leads to a 100%
      acceptance of skin and pancreas allografts for more than 300 days. The recipient
      mice show mixed allogeneic chimerism, and spleen cells from the recipients show
      tolerance to both donor-type and host-type MHC determinants in the assays for
      mixed lymphocyte reaction and generation of cytotoxic T lymphocytes. We have
      confirmed that these strategies are applicable to other animals such as pigs and
      rats. We therefore believe that they will become viable and valuable strategies
      for human organ allografts.

PMID- 10202237
TI  - Mixed allogeneic chimerism to induce tolerance to solid organ and cellular
      grafts.
AB  - Transplantation of solid organs and cellular grafts has become clinical routine
      in the last 30 years. However, the requirement for life-long immunosuppression is
      associated with infections, malignancies and end-organ toxicity. Moreover, the
      treatment fails to prevent chronic rejection. The induction of donor-specific
      transplantation tolerance would solve these problems, but has remained an elusive
      goal. One approach to achieve transplantation tolerance is through hematopoietic
      chimerism. This review outlines different concepts of hematopoietic chimerism
      focusing on macrochimerism. Mixed allogeneic chimerism, also known as
      macrochimerism, is defined as engraftment of hematopoietic stem cells achieved by
      bone marrow transplantation (BMT). It discusses the advantages and limitations of
      the BMT as well as approaches to overcome these limitations in the future.

PMID- 10202238
TI  - Synergetic effects of retrovirus IFN-alpha gene transfer and 5-FU on apoptosis of
      colon cancer cells.
AB  - Gene transfer has advantages in the treatment of a variety of disorders due to
      its selective expression within specific mammalian cells including the most
      primitive stem cells and cancer cells. Several investigators have reported on the
      clinical effects of interferon-alpha (IFN-alpha) or the combination of 5-FU plus
      IFN-alpha on patients with advanced colorectal carcinoma. Therefore, we examined
      the ability of a retrovirus-mediated IFN-alpha gene transfer to infect colon
      cancer cells COLO 201 and the effect of IFN-alpha gene expression alone or in
      combination with other chemotherapeutic drugs as 5-FU. IFN-alpha showed positive
      antitumor activity against COLO 201 cells, whereas 5-FU showed time- and
      concentration-dependent antitumor activity against COLO 201 cells. Furthermore,
      we demonstrated that combination therapy of IFN-alpha gene transfer and 5-FU
      resulted in enhancement of cancer cell lethality. The potentiation increased with
      higher concentrations of 5-FU by 1.5- to 2.1-fold. Our results suggest that
      retrovirus-mediated IFN-alpha gene transfer in COLO 201 cells resulted in
      functional gene expression as assessed by the levels of IFN-alpha mRNA and
      protein; furthermore, the combination of IFN-alpha gene transfer and 5-FU have
      additional effects on the induction of apoptosis. This finding provides an
      experimental basis for possible clinical therapy using retrovirus-mediated IFN
      alpha gene transfer alone or in combination with other chemotherapeutic drugs for
      treatment of colorectal cancer.

PMID- 10202239
TI  - Gene therapy for severe combined immunodeficiency caused by adenosine deaminase
      deficiency: improved retroviral vectors for clinical trials.
AB  - Severe combined immunodeficiency (SCID) caused by adenosine deaminase deficiency
      (ADA-) is the first genetic disorder to be treated with gene therapy. Since 1990
      when the first trial started for 2 patients with ADA- SCID, five clinical trials
      enrolling 11 patients have been conducted with different clinical approaches and
      the results obtained from these trials have recently been reported. According to
      these reports, T cell-directed gene transfer was useful in the treatment of ADA-
      SCID whereas the retroviral-mediated gene transfer to hematopoietic stem cells
      was insufficient for achievement of clinical benefits. This chapter reviews
      several crucial problems inherent in the current retroviral technology based on
      the clinical data observed in these pioneering ADA gene therapy trials and
      presents our new retroviral vector system for the next stem cell gene therapy.

PMID- 10202240
TI  - Adenovirus p53 purging for human breast cancer stem cell products.
AB  - Tumor cell (TC) contamination of stem cell products can contribute to relapse
      after high dose chemotherapy and stem cell rescue. A new purging technology using
      replication-deficient recombinant adenovirus (Adv) containing the p53 tumor
      suppressor gene (Adv-p53) has been suggested to reduce tumor contamination of
      autologous stem cell product. We demonstrate herein a safe and effective Adv-p53
      purging procedure using four human breast cancer TC lines. Multiple parameters
      need to be achieved to successfully purge stem cell products, including a high
      cell:virus ratio, a small incubation volume, a long incubation time and 37
      degrees C rather than room temperature. These parameters are all interrelated and
      equally important for the inhibition of TC clonogenic growth. In our studies, we
      also observed that Adv could nonspecifically inhibit TC clonogenic growth,
      although Adv-p53 treatment led to a significantly greater inhibition of
      clonogenic growth by cells expressing mutated p53. The presence of peripheral
      stem cell (PSC) products was found to decrease the effect of Adv-p53 on TC
      clonogenic growth, suggesting that PSC products could compete with TC for
      infection by recombinant Adv. However, X-Gal staining after incubation with Adv
      containing-galactosidase demonstrated that PSC products were 2, 000-fold more
      resistant to Adv infection than TC. We conclude that a 4-hour incubation of stem
      cell products (2 x 10(8)/ml) with 4 x 10(11) Adv-p53 particles is sufficient to
      completely purge TC with no effect on hematopoietic cell function.

PMID- 10202241
TI  - Retroviral-mediated transfer and expression of the common gamma chain into human
      hematopoietic progenitors.
AB  - The common gamma chain (gammac) of cytokine receptors is mutated in X-linked
      severe combined immunodeficiency, a lethal disorder characterized by the absence
      of both humoral and cellular immune defenses. Allogeneic bone marrow
      transplantation from HLA-identical siblings usually results in complete
      reconstitution of the immune system and is the current treatment of choice.
      Genetic correction and reinfusion of autologous hematopoietic stem cells
      represents an alternative therapeutic approach for those patients who lack
      suitable marrow donors. In this study, we show that retroviral-mediated transfer
      of the gammac gene results in efficient expression in CD34+ cells and high
      transduction rate of colony-forming progenitors.

PMID- 10202242
TI  - Correlation between MRI and short-term clinical activity in multiple sclerosis:
      comparison between standard- and triple-dose Gd-enhanced MRI.
AB  - We assessed the relative sensitivities of standard (SD)- and triple-dose (TD)
      gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) for detecting enhancing
      lesions in different phases of multiple sclerosis (MS) disease activity. Ten MS
      patients were studied with monthly brain MRI scans for a 3-month follow-up (i.e.,
      4 scans were obtained for each patient with both SD and TD). A total of 11
      relapses were recorded and treated with short-term high-dose steroid therapy.
      Enhancing lesion numbers and volumes were significantly higher for TD vs. SD
      scans (p < 0.0001). For both Gd doses, the numbers and volumes of lesions were
      higher during clinical relapses; the differences were statistically significant
      when comparing the results for scans obtained during and after a relapse. The
      gain in sensitivity of TD vs. SD scans for enhancing lesion detection was lower
      during relapses, whilst it was maximum after relapses, although these differences
      did not reach statistical significance. Our data confirm the potential role of TD
      MRI for monitoring MS activity, since, with its higher sensitivity, it may detect
      more subtle blood-brain barrier (BBB) damage. They also suggest that the degree
      of BBB damage in individual lesions changes during different phases of disease
      activity.

PMID- 10202243
TI  - Neurological complications after cardiopulmonary bypass: An update.
AB  - INTRODUCTION: Neurological complications are, at the present time, considered
      among the most important causes of morbidity and mortality after heart surgery.
      We evaluated their importance and risk factors. PATIENTS AND METHODS: We
      retrospectively reviewed 2, 528 consecutive patients who underwent
      cardiopulmonary bypass in a single center. In each one, we attended to previous
      vascular risk factors, such as surgical and postoperative events. We considered
      four categories of neurologic outcome: (1) persistent neurological focal
      deficits, (2) stupor or coma, (3) temporary neurological focal deficits, and (4)
      seizures. We carried out univariant and multivariant statistical analysis,
      looking for predictors of adverse neurologic events. RESULTS: Neurological
      complications occurred in 76 patients (3%); 36 of them (47%) had persistent
      neurological focal deficits, 18 (24%) stupor or coma, 18 (24%) temporary
      neurological focal deficits, and 27 (36%) seizures. Twenty-two patients with
      cerebral adverse outcomes died (29%), the overall mortality among the 2,528 cases
      being 5%. Predictors of risk were aortic aneurysm and aortic valve surgery,
      advanced age, female sex, and the use of intra-aortic balloon pump. A longer
      hospitalization time was noticed among patients with neurological side effects.
      DISCUSSION: Neurological complications are common and serious after heart
      surgery, as we have noticed with this series, the largest up to now, according to
      our review of the literature. They increase perioperative mortality and
      hospitalization time. Neurological morbidity and risk factors in our study are
      similar to those previously published.

PMID- 10202244
TI  - The Barcelona Stroke Registry.
AB  - The Barcelona Stroke Registry was established to collect clinical data of
      hospitalized patients with stroke, in order to study their clinical
      characteristics and outcome. Data were collected over a 17-year period in 3,577
      consecutive patients with first-ever stroke admitted to a stroke unit in two
      university hospitals in the city of Barcelona (Catalonia, Spain). Patients were
      generally admitted within 48 h from stroke onset, were evaluated by a
      neurologist, and clinical data were collected using a standardized protocol. All
      subjects underwent computerized tomography (CT) examination. Data on the 3,577
      patients revealed the following stroke subtypes: cerebral infarction (81%),
      corresponding to the varieties of atherothrombotic (39.5%), cardioembolic
      (17.5%), lacunar (11%), unusual (5%), or unknown (8%); and cerebral hemorrhage.
      We analyzed age distribution (mean age 66 years); risk factors (the most frequent
      being hypertension, present in 54% of cerebral infarctions and in 65% of
      hemorrhages); clinical manifestations (the most salient being abrupt onset in one
      half of the cases; high frequency of decreased consciousness in cardioembolic
      infarction; headache, seizures and nuclear palsy in 'unusual' cerebral
      infarctions; vomiting and coma in hemorrhage); localizations by vascular
      territories; mechanisms of the various stroke subtypes; complications (present in
      one third of patients, with a mortality of 14%), and outcome. Two out of 3
      hospitalized stroke patients are first-ever stroke sufferers. Neuroimaging shows
      a cerebral infarct in 86.5% of cases. Clinical and laboratory investigations
      cannot determine the mechanism of 8% of infarcts and of 23% of hemorrhages. The
      high frequency of medical complications, mortality, and disability highlights the
      need to establish stroke units and stroke registries in order to perform further
      research into the diagnosis and management of patients with cerebrovascular
      disease.

PMID- 10202245
TI  - Sporadic choreas: analysis of a general hospital series.
AB  - The incidence of sporadic chorea among general hospital admissions is unknown,
      and the relation of clinical manifestations and etiological factors to
      neuroimaging findings has been little investigated in this condition. We reviewed
      the 7,829 cases admitted to the neurology departments of two general hospitals
      over 3.25 years and identified 23 (8 male and 15 female) cases of apparently
      sporadic chorea. Analysis of the records of these patients permitted etiological
      classification as follows: drug-induced chorea (5 patients), vascular chorea (6
      patients), chorea-vasculitis (1 patient), Sydenham's chorea (1 patient), AIDS
      related chorea (5 patients) and in 4 patients neither etiological factors nor
      neuroradiological alterations were found. Finally in 1 patient, the genetic test
      for Huntington's disease was positive. Thirteen patients had pathological
      neuroimaging findings; however, in only 3 were basal ganglia lesions considered
      to be the cause of the chorea. We conclude that sporadic chorea is not rare among
      neurological department admissions (we found 2.94 cases per 1,000 admissions) and
      only in a minority of cases is the symptomatology attributable to gross basal
      ganglia lesions; HIV infection is an emerging cause of chorea.

PMID- 10202246
TI  - Familial hemiplegic migraine with cerebellar ataxia and paroxysmal psychosis.
AB  - Familial hemiplegic migraine is a rare autosomal dominant disorder associated
      with stereotypic neurologic aura phenomena including hemiparesis. So far two
      chromosomal loci have been identified. Families linked to the chromosome 19 locus
      display missense mutations within the CACNL1A4 gene. Here we report on a family
      with familial hemiplegic migraine and cerebellar ataxia with recurrent episodes
      of acute paranoid psychosis with anxiety and visual hallucinations associated
      with migraine attacks. Based on the clinical and haplotype evidence indicating
      linkage to chromosome 19 in this family, we hypothesize that a dysfunction of the
      mutated calcium channel may be involved not only in the development of hemiplegic
      migraine but also in the acute psychotic episodes observed in these patients.

PMID- 10202247
TI  - High-dose intravenous immunoglobulin treatment and cerebral vasospasm: A possible
      mechanism of ischemic encephalopathy?
AB  - A 46-year-old woman with a severe polyradiculoneuropathy treated with high-dose
      intravenous immunoglobulin (IVIg) presented an encephalopathy with increased
      blood flow velocities of the middle cerebral arteries (MCAs) detected by
      transcranial Doppler (TCD) studies. The similitude between this observation and
      another case recently reported of a patient suffering from Guillain-Barre
      syndrome (GBS) and cerebral blood flow abnormalities after IVIg treatment
      prompted us to investigate the responsibility of the IVIg therapy in the genesis
      of these blood flow alterations. We studied therefore by TCD 10 consecutive
      patients who underwent this treatment for different reasons. In 1 case we
      observed an asymptomatic, spontaneously reversible increase in the blood flow
      velocities of the MCAs consistent with a vasospasm and occurring 3-10 days after
      completion of the therapy. Stroke and ischemic encephalopathy have been reported
      as possible complications of IVIg treatment. In the case under discussion,
      clinical events appeared shortly after the administration of the IVIg therapy and
      responded favorably to a treatment with nimodipine. Other etiopathogenic
      mechanisms, in particular a CNS vasculopathic process related to the GBS itself,
      have to be considered as well. Further studies, with a larger number of patients,
      are therefore needed to evaluate the underlying mechanisms of blood flow
      abnormalities occurring sometimes in GBS patients after IVIg treatment.

PMID- 10202248
TI  - Near infrared spectroscopy and transcranial Doppler in monohemispheric stroke.
AB  - We simultaneously performed near infrared spectroscopy (NIRS) and transcranial
      Doppler (TCD) to evaluate the effects of hypercapnia as well as of scalp ischemia
      on the blood flow at two different depth levels within the brain and of the scalp
      vessels. A decrease in the backscattered light intensity, meaning an increment of
      blood volume, was detected at the end of hypercapnia in all healthy subjects.
      This decrement was partly masked by ischemia in the cutaneous vessels. In 2
      patients with a monohemispheric lesion in the middle cerebral artery (MCA)
      territory, an increase in NIRS response was found in the healthy hemisphere,
      while in the stroke side the CO2-induced changes were negligible. TCD data showed
      a similar increment of blood flow velocity to the hypercapnia in both
      hemispheres, with no differences between the affected and normal side in 1
      patient, whereas in the second one, no increment was observed on the affected
      side, probably due to internal carotid artery stenosis. The two methods nicely
      integrate: TCD mainly tests subcortical changes in the MCA flow, while NIRS is
      exquisitely sensitive to cortical arterioles and capillary blood flow
      modifications.

PMID- 10202249
TI  - n-Hexane neuropathy caused by addictive inhalation: clinical and
      electrophysiological features.
AB  - To assess the clinical and electrophysiological features of n-hexane neuropathy
      caused by addictive inhalation, 4 patients were studied in the progressive phase.
      The neurological manifestations were characterized by subacute predominantly
      motor polyneuropathy and disease progression despite discontinuance of the
      chemicals, which were similar to those reported in industrial exposure, although
      with a severer degree associated with anorexia and body weight loss.
      Electrophysiological studies showed that all showed multifocal conduction block
      and profound conduction slowing, as well as features of axonal degeneration.
      Sural nerve biopsy showed axonal loss, axonal swelling, and thin myelin probably
      due to retraction by axonal swelling. n-Hexane abuse causes severe subacute
      polyneuropathy. The mixed axonal and demyelinating electrophysiological features
      were consistent with peculiar pathological findings. Conduction block, probably
      due to paranodal myelin retraction or ongoing wallerian degeneration, is very
      frequent and could be responsible for the clinical deficits, especially in the
      early phase of illness.

PMID- 10202250
TI  - Late onset cryptogenic photomyoclonus: case report.

PMID- 10202251
TI  - Simultaneous medullar and cutaneous revelation of a cutaneomeningospinal
      angiomatosis.

PMID- 10202253
TI  - Monitoring the response of AIDS-related progressive multifocal
      leukoencephalopathy to HAART and cidofovir by PCR for JC virus DNA in the CSF.

PMID- 10202252
TI  - Troglitazone not only reduced insulin resistance but also improved myotonia in a
      patient with myotonic dystrophy.

PMID- 10202254
TI  - Acute fulminant multiple sclerosis and plasma exchange.

PMID- 10202255
TI  - Acute motor axonal neuropathy associated with IgM anti-GM1 following Mycoplasma
      pneumoniae infection.

PMID- 10202256
TI  - Intracranial neurinoma revealed by isolated dysphonia.

PMID- 10202257
TI  - Insulin exposure and unifying aging.
AB  - BACKGROUND: Absence of a widely agreed upon central paradigm for mammalian aging.
      OBJECTIVE: Detailed elaboration of a proposed mammalian aging paradigm. METHODS:
      Elaboration of a new theoretical model. RESULTS: Hormonal imbalance-growth factor
      exposure theory (HI-GFE theory) can account for two major aging phenomena: (1)
      decline in mammalian 'reserve capacity' and consequent rise of diseases of
      maintenance, and (2) rise then peaking of most age-associated proliferative
      diseases. Reserve capacity decline via gradual decline in mitochondrial maximal
      energy production (state 3) accounts for the gradual redirection of declined
      maximal energy production toward survival functions like ion pumping to the
      relative detriment of RNA and protein synthesis as seen in lesser synthetic rates
      and slower turnover with consequent gradual cellular impairment. Developmental
      program triggered, and over-ample nutritionally driven, growth factor exposure in
      youth to middle age encourages promotional events that lead to proliferative
      diseases that rise coincident to rapidly declining reserve capacity and
      cumulative increased mutational status of age. CONCLUSIONS: Declining
      mitochondrial state 3 aging energy production status is easily and safely
      reversible with probable consequences of greatly postponing the decline in
      overall 'reserve capacity' which may also improve insulin: growth hormone balance
      and result in lower overall growth factor exposure and consequent longer healthy
      life of a potentially greater magnitude increase in life spans than that seen in
      calorie-restricted animals.

PMID- 10202258
TI  - Interleukin-1 induces lipid peroxidation and membrane changes in rat hippocampus:
      An age-related study.
AB  - BACKGROUND: The proinflammatory cytokine, interleukin-1, is traditionally
      associated with the immune response but recent evidence indicates that it plays a
      role in neuronal function. Its expression is increased in neurodegenerative
      conditions and preliminary evidence suggests that it is also increased with
      increasing age. Receptors for interleukin-1 are differentially distributed in the
      brain with a high density in the hippocampus, where interleukin-1beta exerts
      inhibitory effects on release and calcium channel function. OBJECTIVE: The aim of
      this study was to investigate the possibility that interleukin-1 might lead to
      age-related changes in membrane composition. METHODS: Lipid peroxidation was
      assessed in the presence or absence of interleukin-1beta in hippocampal tissue
      prepared from 4- and 22-month-old rats. These data were analysed in parallel with
      age-related changes in arachidonic acid and interleukin-1beta concentrations in
      the hippocampus. RESULTS: We report that interleukin-1beta increased lipid
      peroxidation in hippocampal tissue prepared from 4- but not 22-month-old rats,
      and that this effect was inhibited by alpha-tocopherol. The attenuated response
      to interleukin-1beta in tissue prepared from aged rats correlated with increased
      expression of endogenous interleukin-1beta. Thus, using an ELISA, we have
      demonstrated an age-related increase in the concentration of interleukin-1beta,
      which is accompanied by an age-related decrease in membrane arachidonic acid.
      CONCLUSION: We propose that increased interleukin-1beta expression impacts on
      membrane composition and therefore contributes to age-related impairments in
      neuronal function.

PMID- 10202259
TI  - Tests used to assess the cognitive abilities of aged rats: their relation to each
      other and to hippocampal morphology and neurotrophin expression.
AB  - BACKGROUND: Aged rodents have proven to be a useful tool in studying age-related
      cognitive decline, particularly with regard to hippocampal function. A number of
      maze tests have been developed to evaluate hippocampal function in aged rodents,
      including the eight-arm radial maze, Barnes circular platform maze and Morris
      water maze. To some extent, these mazes have been used interchangeably to
      evaluate aged animals. Few researchers, however, have examined how performance of
      individual, aged animals compares in these three mazes. OBJECTIVE: The purpose of
      this study was to compare the performances in the three mazes and to examine how
      such performances are related to each other, to hippocampal morphology and to
      neurotrophin gene expression. METHODS: We screened groups of young and old Fisher
      344 x Brown Norway rats for general health and physical abilities, tested the
      animals in the three mazes and examined correlations among performances in the
      mazes and in screening tests. Hippocampal neuron density and expression of
      hippocampal neurotrophin mRNAs were also examined and compared with behavior in
      the three mazes. RESULTS: Aged animals were found to be impaired in all three
      mazes and to have lower hippocampal neuron densities compared with young animals,
      with poor learning behavior significantly correlating with reduced hippocampal
      neuron density. Differences were observed between performance in the different
      mazes, but in general the Morris water maze and Barnes circular platform maze
      were found to give similar results.

PMID- 10202260
TI  - Opinions of elderly people on treatment for end-stage renal disease.
AB  - BACKGROUND: As more people survive into old age, a greater number are becoming
      eligible for dialysis treatment for end-stage renal failure. In the UK the
      elderly have previously been excluded from treatment programmes, and continuing
      financial constraints are unlikely to improve this situation. There are few data
      on the views of elderly subjects on renal replacement treatment. We have,
      therefore, explored the views of elderly subjects in this study. METHODS: 50
      subjects were selected from hospital geriatric wards and nursing homes. A short
      clinical vignette about a 75-year-old patient with renal failure was presented,
      and the subjects were asked to give their opinion on choices made by the patient
      to different treatment options. The subjects were then asked what choice they
      would make if in the same situation. They were asked what level of symptoms they
      would tolerate and for their views on cost and treatment allocation. Important
      contributors to quality of life were also determined for each subject using
      visual analogue scales. RESULTS: 84% of the subjects would choose dialysis
      treatment, and 78% of all elderly would attend hospital as necessary, if their
      symptoms could be relieved. 54% of the in-patient elderly and 83.3% of nursing
      home elderly even when physically disabled and living in a nursing home would
      want dialysis for end-stage renal failure. 74% of all elderly preferred to have
      home dialysis treatment. Only 36% of the subjects thought cost was important when
      allocating dialysis to the elderly. Being independent and free from major
      symptoms was regarded as important for a good quality of life. CONCLUSIONS: In
      this survey, elderly subjects wanted dialysis treatment. Neither age nor cost
      were considered important determinants for resource allocation. Symptom relief
      and maintaining independence were considered the main goals of treatment.

PMID- 10202262
TI  - Visual estimation of biological age of elderly subjects: good interrater
      agreement.
AB  - BACKGROUND: Visual estimation of age can be used as a measure of biological age
      (BA) and has become useful in predicting life expectancy. OBJECTIVE: The aim of
      this study was to quantify the interrater agreement of experienced geriatricians
      in visual estimation of BA. METHODS: In a prospective controlled study, 4
      experienced geriatricians estimated the BA of 43 elderly subjects (mean age 82.5
      +/- 6.0 years) during a short standardized interview, using a checklist of age
      associated changes in appearance, communication and mobility. Interrater
      agreement was calculated by analysis of variance and expressed as the intra-class
      coefficient of correlation (ICCC). RESULTS: The ICCC of the BA estimation was
      0.76 (p < 0.001). Within-subject standard deviation of the estimate was 3. 4
      years. On average, BA was 4.8 (+/-4.4) years lower than chronological age (p <
      0.001). CONCLUSION: Visual estimation of BA based on a simple checklist has a
      good interrater agreement and therefore should be part of geriatric assessment.

PMID- 10202261
TI  - Influence of age on the clinical presentation of prolactinomas in male patients.
AB  - OBJECTIVE: Secreting pituitary adenomas are usually not considered a disease of
      older people. However, in male patients, prolactin-secreting pituitary tumours
      occur at a similar frequency throughout the entire life span, giving the
      opportunity to study in this gender the influence of age on the clinical
      presentation and response to treatment of these tumours. METHODS: We conducted a
      retrospective study including 9 male patients aged >/=60 (range 60-73) years and
      10 aged </=30 (range 17-30) years presenting with a prolactinoma in order to
      compare clinical presentation, results of pituitary function tests, and response
      to dopamine agonist therapy between older and younger patients. RESULTS: Four of
      the 9 elderly as well as the 10 younger patients came to medical attention for
      typical features of male prolactinomas including visual field defect in 5 (2
      elderly), headaches in 2 (1 elderly), impotence in 3 (1 elderly), gynaecomastia
      and/or galactorrhoea in 2, and arrested puberty in 2. The remaining 5 older
      people presented for other various reasons: symptoms related to cortisol
      deficiency in 2, lethargy with clinical signs of hypopituitarism in 1,
      spontaneous multiple vertebral fractures in 1, and incidental discovery of a
      pituitary mass in 1. Basal prolactin levels (3,051+/-4,151 vs. 3,365 +/- 4,949
      microg/l) and mean tumour diameter (30 +/- 16 vs. 25 +/- 13 mm) were similar in
      old and young patients. Cortisol deficiency was significantly more frequent in
      the elderly (n = 6) than in the young (n = 1) patients (p 0.02, Fisher's exact
      test). Secondary hypothyroidism was found in 2 elderly only, but not in young
      patients. Sixteen patients (8 elderly) received bromocriptine therapy for at
      least 6 months with a good tolerance. Normalization of the prolactin levels was
      achieved in 6 older (75%) and 4 younger patients (50%). CONCLUSIONS: The
      presentation of a prolactinoma in the elderly man is very heterogeneous and can
      be misleading. At the time of diagnosis, hypopituitarism is more frequent among
      older than younger patients despite a similar tumour size. We found dopamine
      agonists equally effective in the elderly.

PMID- 10202263
TI  - Age-related change in peripheral nerve conduction: compound muscle action
      potential duration and dispersion.
AB  - BACKGROUND: We investigated the effect of age on nerve conduction parameters with
      special reference to the compound muscle action potential (CMAP) duration and
      duration ratio. METHOD: We examined 295 subjects (aged 15-85 years old) with no
      previous history or present signs of peripheral neuropathy. The subjects were
      divided into 3 groups: young (15-34 years old); intermediate (35-64 years old),
      and old (65-85 years old). RESULTS: CMAP amplitude was lower in the old group
      than in the young group; however, the CMAP ratio (proximal CMAP/distal CMAP) did
      not change with age. The CMAP duration and duration ratio did not differ among
      the 3 groups. The CMAP area was smaller in the old group, but the area ratio was
      almost constant among the 3 groups. CONCLUSION: We suggest that age-related
      changes in CMAP amplitude, duration or area may occur uniformly, at least in the
      forearm and the calf segment, in routine nerve conduction studies. The present
      findings also provide useful and reliable information, regardless of age, in
      diagnosing peripheral neuropathy.

PMID- 10202264
TI  - Homeostasis, thymic hormones and aging.
AB  - The thymic-pituitary axis constitutes a bidirectional circuit where the ascending
      feedback loop is effected by thymic factors of epithelial origin. The aim of the
      present article is, first, to introduce the idea of an immune-neuroendocrine
      homeostatic network in higher animals. Next, the relevance of the thymus in this
      network and the possible role of this gland in the neuroendocrine imbalances
      associated with aging are discussed. A number of studies are next reviewed which
      show that the endocrine thymus produces several bioactive molecules, generally
      called thymic hormones, which in addition to possessing immunoregulatory
      properties are also active on nervous and endocrine circuits. In particular, the
      reported activities of thymosin fraction five, thymosin alpha 1 and thymosin beta
      4 on beta-endorphin, adrenocorticotropic hormone, glucocorticoids, luteinizing
      hormone-releasing hormone and luteinizing hormone secretion in different animal
      and cell models are reviewed. The known hypophysiotropic actions of other thymic
      hormones like thymulin, homeostatic thymus hormone and thymus factor are also
      summarized, and the impact of aging on pituitary responsiveness to thymic
      hormones is discussed. As a conclusion, it is proposed that in addition to its
      central role in the regulation of the immune function, the thymus gland may
      extend its influence to nonimmunologic components of the body, including the
      neuroendocrine system. The early onset of thymus involution might, therefore, act
      as a triggering event which would initiate the gradual decline in homeostatic
      potential that characterizes the aging process.

PMID- 10202265
TI  - Curative and population medicine: bridging the great divide.
AB  - There are gaps in understanding between practicing physicians (curative medicine)
      and those trained in public health and epidemiology (population medicine). In the
      last century, these groups were closer, as physicians played a role in public
      health, sanitation and in the prevention of the spreading of infection. However,
      with the recent extraordinary successes of the biomedical model in explaining
      disease, and the ensuing explosion of remarkable - and expensive - medical
      procedures and treatments, public health, preventive medicine and the population
      approach in general have been overshadowed. In this essay, I try to explain how
      the training of physicians and the daily care of patients may hinder their
      appreciation of the population model. For instance, for many of the myriad
      decisions involved in patient care in daily practice, there is little evidence,
      population derived or otherwise. What little evidence there is may be dominated
      by personal experiences, opinions and values. Additionally, the statistical and
      epidemiologic approach necessary for the maintenance of health and prevention of
      illness may not be valued by practitioners whose training and focus is on
      treating sick people one by one. To illustrate these disparities in
      understanding, examples are given from the NIH Consensus Conference on
      mammography screening for women aged 40-49, and from the use of science in the
      courtroom in adjudicating toxic tort cases. Understanding population medicine
      requires an appreciation of the concepts of chance, probability and statistics
      and of epidemiologic principles, difficult areas for many - including the general
      public. These topics play a small to nonexistent role in the formal training of
      most physicians. Some closing of the gap in understanding may be occurring. It is
      hoped this essay will help.

PMID- 10202266
TI  - Evidence-based medicine and stroke.
AB  - The practice of evidence-based medicine requires the interpretation and use of
      best evidence from a variety of potential sources as it may apply to an
      individual patient. There are three critical steps in the practice of evidence
      based medicine. First, high quality data from randomized controlled trials,
      cohort studies, epidemiological research and other sources must be obtained.
      These results must then be effectively disseminated to health care providers.
      Finally, medical professionals must implement appropriate changes in their
      practices. However, available data suggest that there is a gap between
      physicians' existing stroke prevention and treatment practices and those
      supported by the results of clinical trials and other studies. New strategies
      such as the use of computerized decision support systems are being developed, but
      their impact on process of care, costs, and patient outcomes must be rigorously
      evaluated.

PMID- 10202267
TI  - The effect of apolipoprotein E epsilon4 in the relationships of smoking and
      drinking to cognitive function.
AB  - OBJECTIVES: To investigate the joint effect of the apolipoprotein E epsilon4
      (APOE epsilon4), smoking and drinking on cognitive performance in a population
      based longitudinal study of elderly men. DESIGN AND SETTING: The NHLBI Twin
      Study, a longitudinal cardiovascular study of World War II, white, male veterans.
      PARTICIPANTS: A total of 589 male participants in the third cardiovascular
      examination of this panel and aged 59-69 when assessed for cognitive function.
      OUTCOME MEASURES: Cognitive function assessed by the Mini-Mental State
      Examination, the Digit Symbol Substitution Test, the Benton Visual Retention
      Test, APOE epsilon4 allele frequency and cardiovascular disease (CVD) health
      status. RESULTS: For the sample as a whole, after adjustment for age, education
      and CVD, smoking was significantly associated with poor cognitive function (odds
      ratio (OR) = 2.0, 95% confidence interval (CI) 1.2-3.2, in current smokers
      compared with never smokers), whereas light drinking (one or fewer drinks per
      day) showed a protective effect (OR = 0.6, 95% CI 0.4-0.9 compared with
      abstainers). Stratification by APOE epsilon4 indicated that the protective effect
      of light drinking was stronger and the harmful effect of smoking was weaker among
      APOE epsilon4 carriers than among noncarriers. CONCLUSIONS: These data suggest a
      possible mediating effect of the APOE epsilon4 allele in the relation of smoking
      and drinking to cognitive function in the elderly.

PMID- 10202268
TI  - Prevalence and incidence of clinically diagnosed memory impairments in a
      geographically defined general population in Sweden. The Pitea Dementia Project.
AB  - In the Pitea River Valley all persons with memory impairment that interferes with
      normal life are referred to one hospital department for clinical workup and
      diagnosis. 619 patients were assessed in the department during the years 1990
      1995. Of these, 36.9% had Alzheimer's disease (AD), 30.4% had vascular dementia
      (VaD), 3.0% had a mixed AD/VaD, 3.2% had frontotemporal dementia and 5.3% had
      other forms of dementia. Another 7% had memory impairment but no dementia. The
      overall mean annual incidence rate of clinically relevant dementia was
      295/100,000 persons at risk and the mean prevalence rate was 755/100,000 persons.
      For persons 65 years and older the incidence and prevalence rates were 840 and
      2,150/100,000 persons, respectively. This means that annually, approximately 300
      persons/100,000 population over the age of 40 need medical attention or social
      services.

PMID- 10202269
TI  - Hypotheses concerning roles of dietary energy, cured meat, and serum tocopherols
      in adult glioma development.
AB  - We conducted a pilot study to determine whether: (1) high levels of energy intake
      increase glioma risk; (2) the previously observed relationship between cured meat
      consumption and glioma risk can be attributed to confounding by energy intake,
      and (3) alpha-tocopherol modifies caloric intake and gamma-tocopherol modifies
      cured meat consumption. We identified 40 age-sex-race matched glioma sets, and
      obtained serum vitamin C and alpha- and gamma-tocopherol levels for 23 of these
      sets. Glioma risk increased with quartile of total dietary energy adjusted for
      fat, protein, and nitrite-containing meat consumption (odds ratio = 1.0, 2.7,
      5.8, 8.2; p value for trend test = 0.02). Although positive associations between
      individual cured meats and glioma risk decreased when adjusted for caloric
      intake, the small sample size makes it difficult to interpret the results. Serum
      alpha-tocopherol appeared to modify the effect of calories and serum gamma
      tocopherol may modify the effect of cured meat on glioma risk. While the observed
      interaction is predicted by experimental research, our findings are based on
      small numbers. Larger studies are needed to further evaluate our preliminary
      findings.

PMID- 10202270
TI  - Two consecutive phase II studies of 5-fluorouracil/leucovorin/mitomycin C and of
      gemcitabine in patients with advanced biliary cancer.
AB  - INTRODUCTION: Carcinoma of the biliary system is a rare tumor entity, and
      patients with advanced disease face a dismal prognosis. Because of the absence of
      standard chemotherapy for advanced biliary carcinoma, we have performed two
      consecutive studies to evaluate the clinical potential of 5-fluorouracil,
      leucovorin and mitomycin C as well as the novel antimetabolite gemcitabine in
      this disease. PATIENTS AND METHODS: A total of 39 consecutive patients suffering
      from locally inoperable or metastatic biliary cancer were enrolled in the study
      between March 1994 and October 1997. Twenty patients were treated with leucovorin
      200 mg/m2 and 5-FU 400 mg/m2, both given as intravenous bolus on days 1-4, and
      mitomycin C 8 mg/m2 on day 1 (group A). Treatment cycles were repeated every 28
      days. The second cohort included 19 patients, who received gemcitabine 1200 mg/m2
      on days 1, 8 and 15 with a 2-week interval before the next treatment cycle (group
      B). Treatment was continued for a maximum of 6 cycles in the absence of
      progressive disease in both groups, and endpoints of the study were responses
      rates, survival and toxicity. RESULTS: In group A, 5 patients (25%) had a partial
      response (PR), 6 additional patients (30%) had stable disease (SD) and 9 patients
      (45%) progressed during treatment. The median survival was 9.5 months (range, 3
      14.5) with the median time to progression being 4 months (range, 3-9). In group
      B, 3 patients achieved a PR (16%), 4 showed SD (21%), while the remaining 12
      patients had progressive disease. A median survival of 6.5 months (range, 2-11.5)
      was obtained, and the median time to progression was 2.5 months (range, 1-6+).
      Toxicity was generally mild in both treatment arms, 6 patients in group A
      required dose reductions, while no dose adaptation had to be performed for
      gemcitabine. CONCLUSION: Our data suggest that treatment of advanced biliary
      cancer is feasible and can be safely performed with both regimens applied in our
      study. While administration of gemcitabine has resulted in only mild toxicities,
      its exact impact on the management of advanced biliary cancer should be evaluated
      in a controlled trial.

PMID- 10202271
TI  - A comparative study on ferritin concentration in serum and bilateral
      bronchoalveolar lavage fluid of patients with peripheral lung cancer versus
      control subjects.
AB  - OBJECTIVES: To assess the diagnostic value of bronchoalveolar lavage fluid (BALF)
      ferritin as a lung tumor marker by comparing serum and BALF ferritin
      concentrations in patients with peripheral lung cancer versus control subjects
      with benign lung disease, and to examine the theory of ferritin
      compartmentalization around the tumor area by comparing ferritin concentrations
      in serum and bilateral (affected and unaffected side) BALF in cancer patients.
      METHODS: Four groups of patients were investigated: 10 control nonsmokers, 10
      control smokers, 10 smokers with chronic obstructive pulmonary disease (COPD),
      and 22 patients with primary bronchogenic carcinoma. A bronchoalveolar lavage
      (BAL) was performed in all subjects (both sides in 13 oncological patients, one
      side in the others) and samples of BALF and blood were submitted to biochemical
      analysis. RESULTS: As a lung tumor marker, BALF ferritin showed 54% sensitivity
      and 93% specificity and serum ferritin 22% sensitivity and 93% specificity. A
      significant difference was observed between the two sides in the cancer patients
      (p = 0.033), and between BALF ferritin from the affected side and COPD patients
      (p = 0.025). Greater differences were obtained when BALF ferritin in the affected
      side of cancer patients was compared with values in both control nonsmokers (p <
      0.0001) and control smokers (p < 0.001). CONCLUSIONS: These findings seem to
      confirm the relative diagnostic value of BALF ferritin as a lung tumor marker and
      the theory of ferritin compartmentalization. However, further studies are
      required to clarify the relations between iron and ferritin on the one hand and
      inflammation, tumorigenesis and host response on the other.

PMID- 10202272
TI  - Gross pathologic types of hepatocellular carcinoma in Italy.
AB  - The prevalence and independent predictors of the different macroscopic types of
      hepatocellular carcinoma (HCC) were assessed in 1,073 unselected patients of 14
      hospitals in Italy from May 1996 to May 1997. Solitary HCC was the most common
      cancer type (44.6%), followed by multinodular (44.2%), diffuse (8.4%) and massive
      (2.8%) types. After adjustment for the influence of confounders by multiple
      logistic regression analysis, Child-Pugh grades B and C were found to be
      independent predictors of multinodular (odds ratio, OR, 2.0; 95% confidence
      interval (CI) = 1.5-2.6) and diffuse (OR 2.6; 95% CI = 1.6-4.4) HCC types. These
      findings indicate that the majority of HCC cases are not detected at a
      potentially treatable stage. Delayed detection of HCC is associated with a higher
      likelihood of the multinodular or diffuse gross pathologic type.

PMID- 10202273
TI  - Local control after curative surgery for cancer of the extraperitoneal rectum.
      Twenty years of experience.
AB  - A retrospective study was carried out in 264 patients with low rectal cancer
      surgically treated with curative intent from January 1975 to December 1995 to
      analyze the influence of stapling devices on surgical and disease outcome.
      Patients were classified as follows: group 1 underwent surgery from 1975 to 1980,
      when staplers were not employed, and group 2 from 1981 to 1995, when stapling
      devices were routinely used. The use of stapling devices determined a
      corresponding increase in low anterior resection (LAR) and a decrease in
      postoperative mortality. A statistically significant difference in local
      recurrence rate between abdominoperineal resection (APR) patients and LAR sutured
      cases of group 1 was observed. In T3, N+ cases local recurrence rate was
      comparable in APR patients and LAR cases with stapled anastomosis. Improved local
      control occurred in stapled group 2 patients which was independent of the distal
      clearance. Although APR still plays an important role in treatment of lower
      rectal cancer, results indicated that a similar outcome after stapled LAR can
      also be expected in locally advanced carcinoma of the distal rectum, if accurate
      excision of perirectal tissue is carried out.

PMID- 10202274
TI  - Carboplatin, methotrexate and 5-fluorouracil in combination with
      medroxyprogesterone acetate (JMF-M) in the treatment of advanced or recurrent
      endometrial carcinoma: A Hellenic cooperative oncology group study.
AB  - Twenty-three patients with advanced or recurrent endometrial carcinoma entered a
      prospective study of chemotherapy which consisted of carboplatin (300 mg/m2),
      methotrexate (30 mg/m2), and 5-fluoruracil (500 mg/m2) given on day 1, in a 3
      weekly schedule, in combination with medroxyprogesterone acetate (MPA): 300 mg
      daily, p. o., until progression (JMF-M regimen). None had received prior
      chemotherapy and/or hormonotherapy for metastatic disease. Ten patients had
      received radiotherapy. Response to treatment was evaluated every two courses.
      Objective response was seen in 17 of the 23 patients (74%, 95% confidence
      interval = 52-90%), with 2 long-lasting complete responses (9%). The median
      response duration was 10+ months (3-45+). The median survival was 16+ months (2
      45+). The 2 complete responders, the first in the lung and the second in groin
      nodes, are without evidence or recurrence after 32 and 45 months, respectively.
      The regimen was given on an outpatient basis and was well tolerated. The major
      toxic effects were myelosuppression (less than 14% leukopenia, anemia and
      thrombocytopenia). The MPA-related side effects were: weight gain (22%),
      hypertension (17%) and thromboplebitis (17%). In 2 patients, consolidation
      treatment with MPA was discontinued because of thromboplebitis. In conclusion,
      the JMF-M regimen is highly active with an acceptable toxicity in patients with
      recurrent or metastatic endometrial carcinoma.

PMID- 10202275
TI  - Chronological changes in incidences of polymorphic reticulosis in Korea and
      Japan.
AB  - Lethal midline granuloma (LMG) is a clinical term, which describes a group of
      diseases histologically comprising Wegener's granulomatosis, polymorphic
      reticulosis (PR), and malignant lymphoma of the ordinary type (ML). PR is a
      variant of ML, and is considered to be a type of NK/T cell lymphoma. Our previous
      study revealed the clustering of patients with PR in East Asia including China,
      Korea and Japan. However, the frequency rate of PR varied even among these
      countries, with that of Korea being approximately 5 times higher than that of
      Japan. In the present study, we examined the incidences of each type of LMG,
      especially PR, in Korea (Yonsei University) and Japan (59 university hospitals)
      over time. A total of 102 cases and 655 cases of LMG admitted to Yonsei
      University, Korea from 1977 to 1996 and 59 university hospitals in Japan between
      1965 and 1996, respectively, were examined. The frequency rate of PR per 100,000
      outpatients of ears, nose and throat (ENT) clinics in Korea decreased from 40 to
      20 between the periods of 1977-1989 and 1990-1996. However, there were no
      significant changes in Japan during the period studied.

PMID- 10202276
TI  - Prognostic classification of malignant melanomas by combining clinical,
      histological, and immunohistochemical parameters.
AB  - In a retrospective study the prognostic relevance of clinical, histopathological,
      immunohistochemical, and flow-cytometric parameters in primary malignant
      melanomas was evaluated using both the receiver operating characteristic ROC
      procedure and the logistic regression model. The proteolytic enzymes collagenase
      IV, cathepsin B, and cathepsin D proved to be significant prognostic factors.
      Combining the results obtained with these enzymes with gender, anatomic site,
      tumour thickness, Clark's level, ulceration, pattern of invasive growth, and
      presence of large round cells resulted in greatly improved discrimination between
      metastasized and non-metastasized cases. It is anticipated that this method could
      allow for precise individual prognostic characterization and in particular for
      identification of high-risk patients for adjuvant therapy.

PMID- 10202277
TI  - Prediction of response to 5'-deoxy-5-fluorouridine (5'-DFUR) in patients with
      inoperable advanced gastric cancer by immunostaining of thymidine
      phosphorylase/platelet-derived endothelial cell growth factor.
AB  - BACKGROUND: No reliable method is available for predicting the response to
      chemotherapy in patients with gastric cancer. The anticancer drug 5'-deoxy-5
      fluorouridine (5'-DFUR) is converted into 5-fluorouracil (5-FU) by thymidine
      phosphorylase (dThdPase). We studied the relation between the expression of
      dThdPase in tumor tissue and the response to treatment with 5'-DFUR to determine
      if this enzyme can be used to predict the response to chemotherapy. METHODS AND
      MATERIALS: We performed endoscopic biopsy and studied the expression of dThdPase
      by immunostaining with anti-dThdPase monoclonal antibody in 41 patients with
      inoperable advanced gastric carcinomas before they received multiple-drug
      chemotherapy, including 5'-DFUR. The relation between the expression of dThdPase
      and the response to chemotherapy was studied. We also studied the characteristics
      of positive cells against anti-dThdPase monoclonal antibody. RESULTS: The
      response rate among patients whose tumors were positive for dThdPase expression
      (56.8%, 21/37) was higher than that among patients whose tumors were negative for
      dThdPase expression (0%, 0/4; p = 0.048). Spindle-shaped cells darkly expressing
      dThdPase were sporadically seen surrounding cancer nests in some patients.
      Multiple-antibody immunostaining suggested that these spindle-shaped cells were
      perivascular mesenchymal cells. The response rate was 82.4% (14/17) among
      patients with spindle-shaped cells strongly positive for dThdPase, as compared
      with 29.2% (7/24) among those with spindle-shaped cells weakly positive or
      negative for dThdPase (p = 0.00131). The expression of spindle-shaped cells
      darkly stained with dThdPase was the factor most strongly related to the response
      to chemotherapy (odds ratio = 35.513, p = 0.0027). CONCLUSIONS: The expression of
      dThdPase in stromal spindle-shaped cells may be a useful index in predicting the
      response to 5'-DFUR in patients with gastric cancer.

PMID- 10202278
TI  - MUC1 expression in intramucosal colorectal neoplasms. Possible involvement in
      histogenesis and progression.
AB  - PURPOSE: The mucin core peptide MUC1 often is detectable in colorectal carcinoma
      (CRC) tissue and cell lines. However, whether MUC1 in CRC correlates with tumor
      histogenesis and progression is unclear. We studied the relationship between MUC1
      expression in intramucosal CRC and clinicopathologic features, expression of Ki
      67, and p53 protein, and apoptosis. METHODS: The intramucosal CRC we studied
      included 140 endoscopically or surgically resected lesions, including 106 low
      grade carcinomas and 34 high-grade carcinomas. De novo carcinoma, defined as
      carcinoma with no adenomatous component, represented 9 of 140 tumors. Three
      macroscopic types were identified: 57 lesions were polypoid, 55 were superficial
      and flat, and 28 were granular-type laterally spreading tumors (G-LST). MUC1, Ki
      67, and p53 expression were examined immunohistochemically. Apoptotic cells were
      identified by in situ DNA nick end labeling. RESULTS: MUC1 expression in high
      grade carcinomas was significantly more frequent (p < 0.01) than in low-grade
      carcinomas; expression in adenomas was almost nil. MUC1 expression in polypoid
      carcinomas was significantly more frequent (p < 0.05) than in superficial
      carcinomas or G-LST. MUC1 expression in carcinomas with p53 expression was
      significantly more frequent (p < 0.01) than in carcinomas not expressing p53. No
      significant correlation was found between expression of MUC1 and Ki-67 labeling
      index. MUC1 was expressed more frequently in carcinomas with relatively high
      apoptotic index (p < 0.01). MUC1 expression did not differ between de novo
      carcinomas and those developing from adenomas. CONCLUSIONS: The results suggest
      that MUC1 is likely to be expressed in the course of colorectal carcinoma
      development when p53 protein is overexpressed and apoptosis is prominent.

PMID- 10202279
TI  - Soluble CD44 variant 6 as a prognostic indicator in patients with colorectal
      cancer.
AB  - The expression of CD44v6 is well known as a useful marker of tumor progression
      and prognosis in colorectal cancer. In this study, we evaluated the serum levels
      of soluble CD44 splice variants containing exon v6 (sCD44v6) and examined the
      histological expression of CD44v6 in patients with colorectal cancer. Serum
      samples were obtained from 44 primary colorectal cancer patients before surgery.
      We used enzyme-linked immunosorbent assay to determine the serum levels of
      sCD44v6. The expression of CD44v6 was examined by immunohistochemical staining of
      the primary tumors obtained from the same patients. Both the serum concentration
      of sCD44v6 and the expression of CD44v6 were significantly associated with lymph
      node metastasis (p < 0.05). Furthermore, the serum level of sCD44v6 was higher in
      those patients with CD44v6-positive tumor tissues (154.4 +/- 34.8 ng/ml) than in
      those with CD44v6-negative ones (130.7 +/- 32.3 ng/ml; p < 0.05). The 5-year
      survival rate was significantly lower in patients with high serum levels of
      sCD44v6 (52.4%) than in those with low levels of sCD44v6 (78.0%; p < 0.05), and
      it was also significantly lower in patients with CD44v6-positive cancer (42.1%)
      than in those with CD44v6-negative cancer (84%; p < 0. 01). We concluded that
      preoperative elevation in the serum levels of sCD44v6 might be a prognostic
      indicator for patients with colorectal cancer.

PMID- 10202280
TI  - Clinical significance of mdm2 and p53 expression in bladder cancer. A comparison
      with cell proliferation and apoptosis.
AB  - BACKGROUND: Clinical significance of immunohistochemically detectable level of
      p53 protein has been reported, but with some limitation as a prognosticator of
      bladder cancer patients. Whether or not simultaneous evaluation of mdm2 and p53
      expression in bladder cancer exceed the prognostic significance of conventional
      histological findings, cell proliferation markers and apoptotic parameters
      remains unclear. MATERIALS AND METHODS: The paraffin-embedded materials taken
      from 84 patients with transitional cell carcinoma of the bladder who were treated
      with total cystectomy were used in this study. Immunostainings of p53 protein,
      mdm2 protein and Ki67 antigen were performed using monoclonal antibodies (clone
      DO7, clone 1B10 and clone MIB1, respectively). In addition, the apoptotic cells
      were determined using a terminal deoxynucleotidyl transferase (TdT) mediated dUTP
      biotin nick end labeling (TUNEL) technique. The results were quantitatively
      evaluated using a CAS 200 Image Analyzer (Cell Analysis System, Elmhurst, Ill.,
      USA) and were compared with histological findings and clinical course. RESULTS:
      The mean values of mdm2 expression, p53 immunoreactivity, Ki67 expression and
      apoptotic index were 19.2, 20.5, 22.4 and 0.96%, respectively. Histological grade
      and pT category were significantly positively correlated with 53 immunoreactivity
      (p < 0.05 and p < 0.05, respectively), Ki67 expression (p < 0.005 and p < 0.0001,
      respectively) and apoptotic index (p < 0.01 and p < 0.0001, respectively), while
      both were not correlated with mdm2 expression. Using univariate analysis, the
      prognostic relevance for both survival and disease progression was noted in
      histological grade, pT category, p53 expression, Ki67 index and apoptotic index,
      whereas it was not in mdm2 expression. However, when analyzing the simultaneous
      evaluation of mdm2 and p53 expression (mdm2-p53 category), the relationship of
      the mdm2-p53 category with Ki67 expression and apoptotic index showed a
      statistical significance and a borderline significance (p = 0.0085 and p =
      0.0652, respectively). In addition, the patients with both mdm2(-) and p53(-)
      showed a significant better prognosis as compared with either counterpart of mdm2
      p53 category (p < 0.05 for both). Multivariate analysis revealed only pT category
      and mdm2-p53 category as independent factors for both disease progression and
      survival. CONCLUSIONS: Clinical significance of simultaneous evaluation of mdm2
      and p53 immunostaining proved to be superior over that of cell proliferation
      and/or apoptotic markers when elucidating the biological characteristics of
      bladder cancer.

PMID- 10202281
TI  - Flow cytometry and squamous cell carcinoma of the maxillary sinus: A possible
      prognostic indicator for multimodality intervention.
AB  - Malignant tumors of the paranasal sinuses constitute less than 1% of all
      malignancies. Unfortunately, few prognostic factors have been identified
      regarding the efficacy of interventional therapy. Patients with carcinoma of the
      maxillary sinus frequently present with an advanced stage of disease and
      multimodality therapy is often proposed. Although some tumors appear to be more
      sensitive to preoperative chemotherapy and radiation therapy, a method of
      predicting and evaluating tumor behavior has not been recognized. Introduced as a
      means of identifying cell populations with abnormalities in total DNA content,
      flow-cytometric DNA analysis provides a quick and reliable means of tumor
      characterization for many malignancies. Although nuclear DNA content has been
      implicated as a prognostic factor in an increasing number of tumor types, current
      data on the role of DNA content in head and neck carcinoma is conflicting and
      incomplete. To evaluate the role of flow-cytometric DNA analysis in predicting
      therapeutic alternatives, 22 patients with squamous cell carcinoma of the
      maxillary sinus were reviewed. Patient outcome and histopathologic grade were
      retrospectively compared with flow-cytometric evaluations of paraffin-embedded
      formalin-fixed tumor specimens. Four of sixteen tumors (25%) were found to be
      aneuploid and were also associated with an increased survival rate (p < 0.01).
      This initial data emphasizes the possible usefulness of DNA measurement for
      characterization of squamous cell carcinoma of the maxillary sinus and stresses
      the need for further evaluation.

PMID- 10202282
TI  - Serum level of a soluble receptor for interleukin-2 as a prognostic factor in
      patients with gastric cancer.
AB  - Increased levels of a soluble receptor for interleukin-2 (sIL-2R) have been found
      in the serum from patients with a variety of malignancies. Levels of sIL-2R have
      not previously been examined in a large group of patients with gastric cancer as
      a possible indicator of prognosis. Serum levels of sIL-2R were measured
      preoperatively by an enzyme-linked immunosorbent assay in 121 patients with
      gastric cancer. The preoperative levels of sIL-2R in patients with gastric cancer
      were significantly higher than those in normal controls. An elevated level of sIL
      2R was significantly correlated with certain clinicopathologic features, which
      included depth of invasion, lymph node metastasis, lymphatic vessel invasion,
      blood vessel invasion and clinical stage. The postoperative survival time of
      patients with elevated levels of sIL-2R was significantly shorter than that of
      patients with normal levels. Furthermore, a multivariate analysis using Cox's
      proportional hazards model showed that the combination of levels of
      carcinoembryonic antigen and sIL-2R was an independent indicator of prognosis.
      Thus, the serum level of sIL-2R might be a useful prognostic indicator in
      patients with gastric cancer.

PMID- 10202283
TI  - Bcl-2 expression in non-small cell lung cancers: higher frequency of expression
      in squamous cell carcinomas with earlier pT status.
AB  - Abnormal expression of the bcl-2 gene product (Bcl-2) has been found in a wide
      variety of tumors, including lung cancer. In the present study, a total of 116
      tumor specimens from surgically resected non-small cell lung cancer (NSCLC)
      patients, that were previously studied for p53 protein expression, were analyzed
      with immunohistochemistry for Bcl-2 expression. Forty (34%) of 116 tumor
      specimens showed Bcl-2 expression, which was found to occur more frequently in
      males than females (p = 0.049) and to be associated with smoking (p = 0.047). Bcl
      2 expression was more frequently observed in squamous cell carcinomas (27 of 51,
      53%) than in adenocarcinomas (12 of 55, 22%; p = 0.002), and in pT1 tumors (11 of
      13, 85%) than in pT2 and pT3 tumors (16 of 38, 42%) in squamous cell carcinomas
      (p = 0.01). Bcl-2 expression did not correlate either with p53 protein status. We
      compared Bcl-2 expression in primary tumors and metastatic tumors of regional
      lymph nodes. Of 11 cases with Bcl-2-negative primary tumors, 10 were Bcl-2
      negative in metastatic tumors except 1 case. In contrast, of 10 cases with Bcl-2
      positive primary tumors, 6 lost Bcl-2 expression in metastatic tumors, while the
      remaining 4 cases still showed Bcl-2 expression in metastatic tumors. In the 89
      potentially curatively treated patients, those with Bcl-2-positive and Bcl-2
      negative tumors did not show a significant difference in survival (5-year
      survival rates, 56 and 42%, respectively, p = 0.2 by the generalized Wilcoxon
      test). These data indicate that Bcl-2 expression is frequently observed in
      squamous cell carcinomas with early pT status, and that it does not predict
      prognosis of patients with NSCLC.

PMID- 10202284
TI  - Usefulness of fluorescein angiography in predicting the size of the atrophic area
      after surgical excision of choroidal neovascularization.
AB  - Twenty consecutive patients affected by age-related macular degeneration (AMD)
      complicated by subfoveal and juxtafoveal choroidal neovascularization (CNV)
      underwent a surgical removal of the membrane. The patients were divided into two
      groups: group A = CNVs </=2 months; group B = CNVs >2 months. The surgical
      excision of the CNV was also performed in 10 cases of multifocal choroidopathies
      and idiopathic CNV. The atrophic area after surgery was larger in AMD than in
      multifocal choroidopathies or idiopathic CNV (p < 0.001). In AMD the atrophic
      area after surgical excision of the CNV was larger in group B than in group A (p
      < 0.05). The area of the CNV + the hyperfluorescent halo observed in the late
      phase of fluorescein angiography before surgery was 84.6% of the atrophic area
      after surgery. Our observations could be helpful to the surgeon for a more
      accurate evaluation of the expected size of the atrophic area after surgical
      removal of a CNV, thus allowing a better selection of the patients for whom
      surgery could be of some benefit.

PMID- 10202285
TI  - Relationship between blood flow velocities in retrobulbar vessels and laser
      Doppler flowmetry at the optic disk in glaucoma patients.
AB  - The relationship between blood flow velocities in retrobulbar vessels and blood
      flow at the optic nerve in glaucoma patients was assessed in a prospective study.
      The Heidelberg retina flowmeter (HRF) was used to assess optic nerve head blood
      flow in 13 open-angle glaucoma patients. In the same patients, color Doppler
      imaging (CDI) measurements were obtained from the ophthalmic artery, the central
      retinal artery and the posterior ciliary arteries. Using data for one randomly
      selected eye per subject, correlations between HRF recordings and CDI
      measurements were evaluated by means of Spearman's rank correlation factor. All
      three HRF parameters correlated with CDI measurements obtained from retrobulbar
      vessels. The most marked correlations were those of the HRF parameter 'volume'
      with the end-diastolic velocity in the ophthalmic artery and the medial posterior
      ciliary artery (R = 0.79, p = 0.0012 and R = 0.81, p = 0.0007, respectively), and
      the peak systolic velocity in the lateral posterior ciliary artery (R = 0.82, p =
      0.0006). The present study suggests that glaucoma patients with altered blood
      flow in retrobulbar vessels are likely to show an alteration in optic nerve blood
      flow as measured with the HRF.

PMID- 10202286
TI  - Blood flow velocity in the peripheral circulation of glaucoma patients.
AB  - Using the laser Doppler technique we measured finger blood flow velocity in 25
      untreated primary open-angle glaucoma (POAG), 22 untreated low-tension glaucoma
      (LTG) and 19 age-matched normal subjects. Four blood flow measurements were
      recorded: baseline flow, after immersion in warm water for 2 min (40 degrees C
      maximum flow), after 10 s exposure to cold water (4 degrees C minimum flow) and
      time to recover to baseline flow after cold immersion. Significant differences
      between the LTG group and both the normal and POAG groups were found in a greater
      maximum flow (p = 0.03 and p = 0.01, respectively), a lower minimum flow (p =
      0.04 and p = 0.03, respectively) and a longer recovery time to baseline flow (p =
      0. 0001 for both the normal and POAG groups). A longer recovery time to baseline
      flow (p = 0.008) in POAG was the only difference between the normal and POAG
      groups. Both glaucoma groups had more systemic vascular disease than normal, and
      there were more smokers in the POAG group than normals. Subgroup assessment
      performed with migraine, vascular disease and smoking subjects excluded from the
      analysis did not alter the overall results. We conclude that systemic vasospasm
      is a strong feature of low-tension glaucoma.

PMID- 10202287
TI  - Peripheral choriovitreal neovascularization in proliferative diabetic
      retinopathy: histopathologic and ultrastructural study.
AB  - We describe the histopathologic and ultrastructural evidence of choriovitreal
      neovascularization in the peripheral fundus of a non-vitrectomized eye with
      proliferative diabetic retinopathy (PDR). One eye with PDR was surgically
      enucleated because of neovascular glaucoma and studied with light and electron
      microscopy. The eye had neovascular membranes at the ora serrata of the
      peripheral fundus. The newly formed vessels originated from the choroid, passed
      through Bruch's membrane and the retina, and extended into the vitreous. These
      vessels had either developing or mature characteristics. The endothelial cells of
      the developing vessels contained a bulky cytoplasm with many intracytoplasmic
      filaments, ribosomes and rough endoplasmic reticulum. Budding endothelial cells
      were frequently found in the developing vessels. The endothelial cells of the
      mature vessels had attenuated cytoplasm and fenestrations with diaphragms. These
      observations suggest that choriovitreal neovascularization in the peripheral
      fundus is one of the features of PDR.

PMID- 10202288
TI  - Primary orbital leiomyoma and leiomyosarcoma.
AB  - A case of an extremely rare primary orbital leiomyoma in a 25-year-old male
      patient is presented who had a lifelong history of deviation of the left eye
      globe with slight enophthalmos and reduced motility. Because of pain and
      increasing deviation of the eye the tumor was totally resected. On histologic
      examination the tumor showed ossification which is extremely rare so that a
      calcifying fibroma had to be ruled out. In immunohistochemistry, however, this
      tumor stained with smooth muscle antigen. Less than 2% of cells stained positive
      for Ki-S1, a proliferation marker. The second case is a rare primary orbital
      leiomyosarcoma in an 84-year-old female patient that showed massive growth. After
      exenteration histologic examination showed a dedifferentiated highly malignant
      soft tissue tumor which expressed desmin and smooth muscle actin but was negative
      for myoglobin, S-100 and HMB-45.

PMID- 10202289
TI  - Evaluation of the peripherin/RDS gene as a candidate gene in families with age
      related macular degeneration.
AB  - Age-related macular degeneration (AMD) is a heterogeneous group of disorders and
      is the leading cause of blindness in the elderly. While degeneration changes in
      the macula can occur at any time in life, it is the most common cause of severe
      visual impairment with advancing age. The disease affects approximately 11
      million Americans and causes loss of central vision, impairing activities such as
      reading. The exact cause of the disorder is not known. In this report, we studied
      two unrelated families having familial-type AMD, with the assumption that
      mutations in the peripherin/retinal degeneration slow (RDS) gene could contribute
      to the disease phenotype. Our extensive analyses have identified two silent
      mutations (84D and 106V) in one family in the same allele of exon 1 which
      segregated in 3 patients with AMD. However, the fourth affected individual in the
      same family, as well as 40 normal controls, did not contain this mutation.
      Further analysis of exon 2 and exon 3 in both families did not show any other
      sequence alterations. Since one of these silent mutations (106V) has been
      reported to exist in certain general populations and the other mutation (84D)
      failed to segregate completely in the family, it is unlikely that these mutations
      are pathogenic. The results of the study suggest that the peripherin/RDS gene is
      not a major factor responsible for AMD in the families analyzed.

PMID- 10202290
TI  - Leber's hereditary optic neuropathy mitochondrial DNA mutations at nucleotides
      11778 and 3460 in multiple sclerosis.
AB  - OBJECTIVES: Leber's hereditary optic neuropathy (LHON) can be difficult to
      distinguish from optic neuritis seen in multiple sclerosis (MS). About half of
      the LHON patients harbor a mutation at nucleotide (nt) 11778 in the mitochondrial
      (mt) DNA. In addition, mutations at nt-3460 and nt-14484 have been associated
      with LHON. An association of LHON and MS has been suspected for decades, and,
      recently, the LHON nt-11778 and nt-3460 mtDNA mutations have been found in
      several patients with MS or MS-like disease. We attempted to determine which MS
      patients should be evaluated further for LHON mutations. METHODS: We screened 103
      clinically definite MS patients (age range from 18 to 72 years, 27 men and 76
      women) for the LHON nt-11778 and nt-3460 mtDNA mutations. RESULTS: Neither
      mutation was identified in the patients. CONCLUSIONS: Our findings confirm
      previous reports which found that both LHON mutations are rare in unselected MS
      patients. The reports to date suggest that MS patients with peripapillary
      teleangiectasia typical of LHON, with relatives harboring LHON or with early
      severe bilateral optic neuropathy, particularly if female, should be further
      evaluated for LHON mutations.

PMID- 10202291
TI  - Blindness incidence in Germany. A population-based study from Wurttemberg
      Hohenzollern.
AB  - Few data on the incidence of blindness in Germany are available. We analysed
      causes of legal blindness for the region Wurttemberg-Hohenzollern (population 5.5
      million) in order to help fill in this gap. MATERIAL AND METHODS: Population
      based investigation on the incidence of legal blindness (visual acuity <1/50)
      based on materials from the social services. Age-dependent blindness incidences
      were modelled via logistic regression models. RESULTS: 647 blind persons were
      newly registered in 1994 (blindness incidence 11.6/100,000). The blindness
      incidence is moderate in infants (4.5/100,000) and decreases further during
      childhood. At the age of 20 years, the incidence again rises to the former level
      and remains relatively constant. After the age of 60 years, the incidence
      increases sharply: 5-year odds ratios are 1.76 (CI: 1.68-1. 85) in women and 1.72
      (CI: 1.60-1.84) in men. The blindness incidence is higher in women, 15.6/100,000,
      compared to 12.2/100,000 in men. The major causes of blindness are: macular
      degeneration, 3. 92/100,000; diabetic retinopathy, 2.01/100,000; glaucoma,
      1.6/100, 000; high myopia, 0.77/100,000; optic atrophy, 0.68/100,000; central
      nervous system-triggered blindness; 0.56/100,000, and tapetoretinal
      degenerations, 0.52/100,000. DISCUSSION: Due to monetary incentives for the blind
      persons, social service files offer accurate and complete data. Besides macular
      degeneration, glaucoma and diabetic retinopathy are major causes of blindness.
      Thus, this study suggests further blindness prevention activities for diabetic
      retinopathy and glaucoma.

PMID- 10202293
TI  - Chondroplast: A new material for eyelid reconstruction.
AB  - After tumor excision both lamellae of the eyelid require reconstruction in order
      to achieve good functional and cosmetic results. The tarsus is replaced either by
      autologous or heterologous material. We used Chondroplast as a tarsal replacement
      in 25 patients who had undergone extensive tumor excision. Chondroplast is a beta
      irradiated bovine cartilage. A 1-mm-thick lamella is fixed to the rest of the
      tarsal plate or the canthal tendon and positioned in a preformed pocket or the
      conjunctiva and a thin layer of orbicularis muscle and skin. All implants took
      well. Postoperative results, lid closure and cosmetic appearance were excellent.
      No complications such as infection or loss of the implant occurred. The
      advantages of Chondroplast are: its availability in large pieces, no need for
      harvesting procedures and good biocompatibility.

PMID- 10202292
TI  - Ultrastructural effects of topical beta-adrenergic antagonists and an alpha
      adrenergic agonist on the rabbit cornea.
AB  - In the present study the effects of beta-adrenergic antagonist and alpha
      adrenergic agonist drugs on rabbit corneas were evaluated in vivo by using
      transmission electron microscopy. Twenty-four New Zealand albino rabbits were
      divided into six groups according to the drug applied. The rabbits to which only
      balanced salt solution (BSS) or BSS and benzalkonium chloride (BAC) were applied
      were taken as the control groups. The other four groups consisted of the rabbits
      to which Timoptic 0.5%, Betagan 0.5%, Betoptic 0.5% and Iopidine 1% were applied,
      respectively. All of drugs were instilled topically twice daily for 6 weeks. In
      the BSS group, all layers of the cornea were ultrastructurally normal. In the BSS
      and BAC group slight epithelial and endothelial changes were found. However, in
      the other groups, loss of microvilli, increase in glycogen particles, nuclear
      indentation, widening of the intercellular spaces and cytoplasmic vacuolization
      in epithelium were observed. No significant abnormality was found in the basal
      lamina, stroma and Descemet's membrane. Slight ultrastructural changes were noted
      in the endothelium such as vacuolization due to dilatation of the endoplasmic
      reticulum cisternae and focal cytoplasmic lytic areas. The results of this study
      indicate that various ultrastructural changes occur in groups treated with
      antiglaucomatous drug and that topical treatment with timolol and apraclonidine
      for 6 weeks is more toxic to the rabbit cornea than levobunolol and betaxolol.

PMID- 10202294
TI  - Tumor growth of a choroidal malignant melanoma and aqueous flare. Report of a
      case.
AB  - We report the use of the laser flare-cell meter (LFCM) in monitoring blood-ocular
      barrier breakdown induced by a choroidal malignant melanoma in an 88-year-old
      white male, who refused enucleation or radiation treatment. During a follow-up of
      16 months, aqueous flare values measured with the LFCM increased from 12.8 to
      26.5 photon counts/ms with continuous tumor growth from a height of 7.9 to 18 mm.
      Our finding of increasing flare values with tumor growth appears to confirm the
      observation that aqueous flare is influenced by the size of uveal malignant
      melanomas. Quantification of aqueous flare with the LFCM may be helpful in the
      follow-up of eyes with intraocular tumors.

PMID- 10202295
TI  - Vogt-Koyanagi-Harada syndrome in an 11-year-old Boy.
AB  - An 11-year-old boy complained of headache, slight fever and decreased visual
      acuity. Intracameral cells and serous retinal detachment were found in both eyes.
      Pleocytosis was seen in the cerebrospinal fluid. Bilateral uveitis diminished
      rapidly in response to corticosteroid treatment. Depigmentation of the fundi
      developed several months later. We believe that Vogt-Koyanagi-Harada syndrome in
      a child, as demonstrated in our patient, may be uncommon.

PMID- 10202296
TI  - Ocular changes in mucopolysaccharidosis IV A (Morquio A syndrome) and long-term
      results of perforating keratoplasty.
AB  - BACKGROUND: The mucopolysaccharidoses (MPS) are an inhomogeneous group of
      disorders of errors in the carbohydrate metabolism with severe ocular involvement
      (corneal opacification, retinal degeneration, optic atrophy). PATIENT
      PRESENTATION: We report on a boy aged 12 years, with Morquio A (MPS IV A)
      syndrome. Ocular findings: progressive pseudoexophthalmus due to shallow orbits,
      increasing corneal stromal clouding, intermittent dissociated manifest nystagmus
      of the left eye, nyctalopia. Visual acuity OD cc = 0.16, OS cc = 0.05.
      Electrophysiology: changes suggesting a symptomatic tapetoretinal degeneration
      and optic atrophy. TREATMENT AND COURSE OF DISEASE: OS: perforating keratoplasty.
      Postoperative improvement of visual acuity to 0.25 for nearly a year, followed by
      progressive reopacification of the corneal graft. Both eyes: progressive signs of
      tapetoretinal degeneration and optic atrophy. Visual acuity now reduced to OD
      0.05, OS 0.1. CONCLUSIONS: Success of a keratoplasty is limited by (1)
      reopacification of the cornea, (2) visual impairment due to (a) retinal
      degeneration and (b) optic atrophy. The indication for perforating keratoplasty
      has to be thought about very carefully in these multimorbid patients. In our
      patient, beside progressive visual impairment there is a progressive deafness
      which dominates his social and school life. Attending school is severely
      complicated by the double handicap. Perforating keratoplasty enabled the boy to
      attend a school for physically handicapped without a special low-vision care for
      another year. Progressive visual loss without further treatment options now
      renders optical and electronic low-vision aids necessary. Although the time of
      improved visual acuity lasted less than a year, we think patients with a life
      expectancy of less than 20 years should have every possible improvement of their
      situation - even if it does not last permanently. We therefore propose
      perforating keratoplasty in spite of insufficient long-term results.

PMID- 10202298
TI  - Significant immediate and long-term reduction of astigmatism after lateral rectus
      recession in divergent Duane's syndrome.
AB  - Duane's syndrome is associated with anisometropia and amblyopia. We encountered 1
      patient with right divergent Duane's syndrome (type 2 according to Huber's
      classification) with high astigmatism of the right eye and a head turn. In order
      to improve the head turn and thereby avoid eccentric gaze through the glasses,
      the right lateral rectus muscle was recessed by 7.75 mm. Postoperatively, the
      amount of astigmatism was reduced by 1.5 dpt with no change of the axis. This
      change of refraction remained stable over a follow-up time of 18 months.

PMID- 10202297
TI  - Ocular filariasis: not strictly tropical.
AB  - A 65-year-old man consulted for a discomfort in the right eye that had suddenly
      appeared the evening before. The examination revealed a white worm localized
      under the temporal bulbar conjunctiva. After extraction, the parasitological
      characteristics identified the worm as Dirofilaria repens (Nochtiella subgenus).
      This is a parasite of canids and felids, usually nonpathogenic to humans, but
      which can be transmitted through mosquito bites, especially around the
      Mediterranean basin. The simple extraction of the worm, encysted under the skin
      or under the conjunctiva, cures the patient.

PMID- 10202299
TI  - High-grade pediatric spinal cord tumors.
AB  - Our institutional experience with high-grade pediatric spinal cord tumors
      includes 11 children treated during the period of 1981-1997. All patients
      underwent a biopsy or an attempt at resection and received postoperative
      radiation therapy. Three patients had a gross-total resection of their primary
      tumor, 6 patients had a subtotal resection and the remaining 2 were biopsied.
      Histologically, these tumors were characterized as anaplastic astrocytoma (n =
      6), glioblastoma multiforme (n = 3) or anaplastic oligodendroglioma (n = 2).
      Three patients were treated with craniospinal irradiation (38-48 Gy) in addition
      to a boost to the residual tumor. The median dose to the primary site for all
      patients was 48.6 Gy (range 38-55 Gy). The median overall survival was 13 months
      (range 8-149 months). Only 2 patients were alive at 138 and 149 months following
      radiation therapy. The median progression-free survival following radiation
      therapy was 10 months (range 2-80 months). There was no difference in progression
      free or overall survival for those diagnosed with glioblastoma multiforme when
      compared to patients diagnosed with anaplastic astrocytoma or anaplastic
      oligodendroglioma. The pattern of failure was either diffuse or local. For the
      patients who failed diffusely (n = 6), the median progression-free survival was 2
      months compared to 23 months for those whose failure was entirely local (p <
      0.01). The median overall survival was significantly shorter for those who failed
      diffusely compared to those who failed locally (10 vs. 37 months, p < 0.01). High
      grade spinal cord tumors in children have a poor prognosis based on this report.
      It is important to document the extent of disease accurately prior to the
      initiation of radiation therapy, since a subset of these patients progress
      rapidly outside of the field of irradiation.

PMID- 10202300
TI  - A case of cerebrospinal fluid eosinophilia associated with shunt malfunction.
AB  - A 3-month-old female patient presented with a meningomyelocele at the lumber
      region associated with congenital hydrocephalus. She underwent
      ventriculoperitoneal (V-P) shunt surgery using the Sophy system. The shunt system
      was replaced due to a malformation. Following replacement, the patient presented
      with cerebrospinal fluid (CSF) eosinophilia at the age of 8 months. The
      eosinophilic granulocytosis of the CSF improved dramatically following systemic
      prednisolone administration. CSF eosinophilia without accompanying inflammation
      or pyrexia in the present case may have resulted from an allergic response to a
      foreign material such as the silicone tube pressure valve of the Sophy system or
      the sutures rather than bacterial or fungal infection. Based on our results, we
      believe that some patients may experience CSF eosinophilia following
      postoperative V-P shunt due to an allergic reaction to the shunt equipment.
      Prompt steroid treatment can produce spontaneous regression in such cases.

PMID- 10202301
TI  - Third ventriculostomy versus cerebrospinal fluid shunt as a first procedure in
      pediatric hydrocephalus.
AB  - BACKGROUND: Third ventriculostomy (TV) has been reported to be efficacious for
      diverse causes of obstructive hydrocephalus in pediatric patients, and preferable
      to a first CSF shunt (CS) in those eligible. We reviewed the respective failure
      rates in a prospective cohort of patients at our institution. METHOD: All
      patients having either TV or CS (i.e ventriculoperitoneal shunt) over the period
      1987 to 1997 were prospectively entered into a database. To compare homogeneous
      patients, only diagnoses of either aqueductal stenosis or tumor were considered.
      Failure was defined as any subsequent surgical procedure for CSF diversion.
      Kaplan-Meier curves were constructed to determine survivorship. A multivariable
      Cox model using time-dependent covariates was constructed. RESULTS: There were 32
      TV and 210 CS patients: 14 (44%) and 95 (45%) failed, respectively. TV patients
      were older (median age = 8.1 vs. 3.6 years) and had a higher incidence of
      aqueductal stenosis (53 vs. 25%). There was no statistically significant
      difference between the two procedures based on bivariate analysis (p = 0.87) and
      on multivariable analysis using the Cox model after adjusting for the potential
      confounders (p = 0.66, hazard ratio = 1.19, 95% confidence interval = 0.55-2.56).
      CONCLUSION: Failure from TV is not unlike that of CS when analyzed by survival
      methods. Larger prospective series are needed to look at specific subgroups who
      may benefit from TV. Quality of life and clinical outcome measures are also
      required to analyze the difference between these two procedures.

PMID- 10202302
TI  - Intraoperative angiography in the management of pediatric vascular disorders.
AB  - We reviewed our experience with intraoperative angiography in the management of 7
      cerebral aneurysms and 15 arteriovenous malformations (AVMs) in children over the
      past 5 years. The patients ranged from 4 months to 18 years of age with a mean
      age of 9 years. In 4 of the 22 cases, angiography provided information that led
      to changes during surgery. In 3 cases, the intraoperative angiogram revealed
      residual AVMs that were then completely resected. In 1 patient with an anterior
      circulation aneurysm, intraoperative studies revealed findings which resulted in
      clip repositioning. Intraoperative angiography added a mean of 43 (+/-19) min to
      the operative time, with a mode of 40 minutes. There was 1 complication, a groin
      hematoma that readily resolved. Intraoperative angiography prolongs to operative
      course; however, it is a useful adjunct to the management of vascular disorders
      in children. We now routinely use and recommend intraoperative angiography to
      assist with the surgical management of vascular malformations in children.

PMID- 10202303
TI  - Spontaneous dural sinus thrombosis in children.
AB  - The clinical course of spontaneous dural sinus thrombosis in children varies from
      indolent to fulminant. Although many different etiologies for the development of
      dural sinus thrombosis have been described, a full recovery can be anticipated in
      most children following rehydration and the administration of systemic
      antibiotics. Steroids, systemic anticoagulation and intrasinus thrombolysis may
      be beneficial in selected patients, although the efficacy of these therapies has
      not been established prospectively in children. We reviewed 12 pediatric patients
      with spontaneous dural sinus thrombosis (1978-1998) to determine the etiology,
      clinical course and best treatment options. In the absence of a hypercoagulable
      state, pediatric patients generally recover well with rehydration and antibiotics
      and do not require anticoagulation.

PMID- 10202304
TI  - An unusual case of cephalocele associated with lipoma of corpus callosum.
AB  - Cephalocele is a part of the family of neural tube defects. Although the
      frequency has ranged from 1 per 2,400 to 1 per 12,500 live births, the true
      incidence has been hidden in stillborns, underreferral of massive defects and
      early pregnancy losses. It has been suggested that the size, the content of the
      sac and associated hydrocephalus were unfavorable factors for the prognosis.
      Cephaloceles may occur as isolated malformations or together with other
      anomalies, and associated abnormalities are present in up to 50% of the cases. We
      report an unusual case of encephalocele associated with lipoma of corpus
      callosum, and the features of magnetic resonance imaging are discussed.

PMID- 10202305
TI  - Bilateral epidural hematoma in a pyknodysostotic child.
AB  - Pyknodysostosis is a rarely encountered disease. It is characterized by abnormal
      facial development, fragility of the bones with relatively mild trauma, cranial
      abnormalities including widely opened sutures and fontanels frontal bossing,
      wrinkled skin, finger and nail abnormalities. In the literature, pyknodysostosis
      was reported only as case reports. Here, we describe a pyknodysostotic child with
      a bilateral parietal epidural hematoma, caused by a relatively mild head trauma.
      He was operated on, and the hematoma was evacuated through two different parietal
      craniotomies. We reported this case, since pyknodysostosis is a rare disease, and
      our case is the first one who had a surgical intervention as well as being the
      first with an epidural hematoma in pyknodysostosis.

PMID- 10202306
TI  - Growing skull fracture of the orbital roof. Case report.
AB  - Growing skull fractures are rare complications of head trauma and very rarely
      arise in the skull base. The clinical and radiological finding and treatment of a
      growing fracture of the orbital roof in a 5-year-old boy are reported, and the
      relevant literature is reviewed. The clinical picture was eyelid swelling.
      Computed tomography (CT) scan was excellent for demonstrating the bony defect in
      the orbital roof. Frontobasal brain injury seems to play an important role in the
      pathogenesis of the fracture growth. Growing skull fracture of the orbital roof
      should be considered in the differential diagnosis in cases of persistent ocular
      symptoms. Craniotomy with excision of gliotic brain and granulation tissue, dural
      repair and cranioplasty is the treatment of choice.

PMID- 10202307
TI  - Large chronic cephalohematoma without calcification.
AB  - Cephalohematomas following birth normally resorb within the 1st month of life. In
      cases of prolonged resorption, over greater than 1 month, cephalohematomas
      typically begin to calcify. We report the case of a 3-month-old child with a
      persistent, large cephalohematoma that did not calcify. After observation alone
      failed to demonstrate a decrease in the size of the hematoma, 30 cm3 of old blood
      was aspirated, and the patient's head was wrapped. Unlike calcified
      cephalohematomas, this noncalcified lesion did not require open surgical
      intervention. A treatment protocol for cephalohematomas is presented.

PMID- 10202308
TI  - Spontaneous resolution of a cervicothoracic syrinx in a child. Case report and
      review of the literature.
AB  - A child with near complete spontaneous resolution of a cervicothoracic syrinx and
      improvement in a Chiari type I malformation without surgical intervention is
      presented. The child was followed clinically with serial magnetic resonance (MR)
      imaging and has remained neurologically stable over an 11-year period. To our
      knowledge, only 3 pediatric cases of spontaneous resolution of a spinal cord
      syrinx as documented by MR imaging without surgical intervention have been
      reported. This case contributes to the literature on the natural history of
      syringes.

PMID- 10202309
TI  - A 16-year-old male with Noonan's syndrome develops progressive scoliosis and
      deteriorating gait.

PMID- 10202310
TI  - Medulloblastoma with diffuse subarachnoid involvement.

PMID- 10202311
TI  - Severe pediatric head injury: myth, magic, and actual fact. Concerning the
      article by Johnson and Krishnamurthy. Pediatr Neurosurg 1998;28:167-172.

PMID- 10202312
TI  - The lung in the immunocompromised patient. Infectious complications Part 1.
AB  - Pulmonary infections are a major cause of morbidity and mortality in the
      immunosuppressed patient. Among the infections encountered are Pneumocystis
      carinii, mycobacterial, fungal, and bacterial infection. In this review, we will
      discuss these various possible infections, their frequency of occurrence, and
      their clinical presentation in the various immunosuppressed groups.

PMID- 10202313
TI  - Clearance in small ciliated airways in allergic asthmatics after bronchial
      allergen provocation.
AB  - BACKGROUND: Asthma tends to affect mucociliary clearance, as assessed from
      measurements in large airways. However, there is no knowledge about clearance in
      the smallest airways of the tracheobronchial region in acute exacerbation of
      asthma. OBJECTIVE: The aim of the study was to investigate clearance from the
      bronchiolar region in patients with allergic asthma in a situation resembling a
      mild acute exacerbation of the disease. We also aimed to compare clearance data
      with corresponding data found for healthy subjects and asthmatics on therapy.
      METHODS: Tracheobronchial clearance was studied twice in 9 patients with mild
      asthma of the allergic type after inhalation of 6 microm (aerodynamic diameter)
      monodisperse Teflon particles labelled with 111In. At one exposure, inhalation
      was performed 4 h after bronchial provocation with an allergen the patients were
      allergic to. The second exposure was a control measurement. The particles were
      inhaled at an extremely slow flow, 0.05 liter/s, which gives deposition mainly in
      the small ciliated airways (bronchioles). Lung retention was measured at 0, 24,
      48 and 72 h. RESULTS: All patients demonstrated an early asthmatic reaction of
      varying degree after bronchial provocation. There was significant clearance of
      radioaerosol in each 24-hour period for both exposures, with the possible
      exception of the period between 24 and 48 h for the provocation exposure, with
      similar fractions of retained particles at all points of time. The retained
      fractions were significantly larger compared to a group of healthy subjects and
      asthmatics on regular treatment with anti-inflammatory drugs. CONCLUSIONS: Our
      results indicate that in allergic asthmatics a bronchial allergen provocation
      with an early asthmatic reaction does not significantly influence overall
      clearance from the bronchiolar region. However, in the present group of patients,
      retention in small ciliated airways was significantly higher compared to healthy
      subjects and asthmatics on regular treatment.

PMID- 10202314
TI  - Comparison of the bronchodilator effects of salbutamol delivered via a metered
      dose inhaler with spacer, a dry-powder inhaler, and a jet nebulizer in patients
      with chronic obstructive pulmonary disease.
AB  - The aim of this study was to compare the bronchodilator effects of salbutamol
      delivered via three different devices: a dry-powder inhaler (DPI), a metered-dose
      inhaler (MDI) with a large-volume spacer and a jet nebulizer (NEB) in patients
      with stable chronic obstructive pulmonary disease (COPD). Ten male patients with
      stable COPD [age: 67.2 +/- 3.8 years, forced expiratory volume in 1 s (FEV1):
      1.56 +/- 0.32 liters] were studied in a randomized, double-blind and crossover
      manner. Each patient received 200 or 1, 000 microg salbutamol via an MDI with an
      InspirEaseTM spacer, a RotahalerTM, or a DeVilbiss 646(TM) nebulizer (NEB), or
      matching placebo on 7 separate days. Spirometry was performed before and 15, 30,
      60, 90, 120, and 240 min after inhalation. With the 200- microg dose, only DPI
      produced a small but greater response in maximum FEV1 and in area under the time
      response curve (AUC-FEV1) compared with placebo. With the 1,000- microg dose, DPI
      and MDI produced equally greater improvements in both maximum FEV1 and AUC-FEV1
      than NEB. An equal bronchodilating effect can be obtained using either DPI or MDI
      with a spacer device, whereas the NEB was less effective when the same dose was
      administered.

PMID- 10202315
TI  - Suppression of airway inflammation by theophylline in adult bronchial asthma.
AB  - BACKGROUND: Chronic continuous airway inflammation caused by eosinophils has been
      noted to play critical roles in the pathophysiology of bronchial asthma, in
      addition to reversible obstruction and hypersensitivity of the respiratory tract.
      Therefore, suppression of chronic airway inflammation has become more important
      in asthma treatment. Although theophylline has been a conventionally used
      bronchodilator, it has been recently reported to have concurrent anti
      inflammatory effects. OBJECTIVE: Accordingly, we studied the effects of a slow
      release theophylline preparation, Theolong, on airway inflammation. METHODS:
      Administration of Theolong 400 mg/day to 24 patients with mild or moderate asthma
      and measuring eosinophil cationic protein (ECP), a marker of airway inflammation,
      and eosinophils in sputum and peripheral blood at 4 and 8 weeks. RESULTS: As a
      result, sputum ECP, serum ECP and sputum eosinophil count (%) were significantly
      lowered after 4 and 8 weeks. CONCLUSION: Thus, in the theophylline-administered
      group, slow-release theophylline, Theolong, was effective in treating asthma,
      with anti-inflammatory effects on inflammatory cells besides its bronchodilator
      action.

PMID- 10202316
TI  - Nasopharyngeal symptoms in patients with obstructive sleep apnea syndrome. Effect
      of nasal CPAP treatment.
AB  - BACKGROUND: Nasal side effects are often reported during nasal continuous
      positive airway pressure (CPAP) treatment of obstructive sleep apnea syndrome
      (OSAS) and may make the use of nasal CPAP difficult. OBJECTIVE: The aim of this
      study was to evaluate the effect of nasal CPAP on nasopharyngeal symptoms in OSAS
      patients. METHODS: The frequency and severity of nasopharyngeal symptoms and
      signs were prospectively evaluated in 49 consecutive OSAS patients (37 men, 12
      women, mean (SD) age 54 (7) years, body mass index 35 (6) kg/m2) immediately
      before and after 6 months' treatment with nasal CPAP. RESULTS: Nasopharyngeal
      symptoms were common already before starting nasal CPAP: 74% of patients reported
      dryness, 53% sneezing, 51% mucus in the throat, 45% blocked nose, and 37%
      rhinorrhea. During nasal CPAP treatment, severity and frequency of sneezing (75%)
      and rhinorrhea (57%) increased. This increase was related to the season when
      nasal CPAP was applied, and was more profound in winter than in summer. Mild
      abnormalities on rhinoscopy and paranasal sinus X-rays were common both at
      baseline and at follow-up with no significant change during treatment.
      CONCLUSIONS: Nasopharyngeal problems were found to be frequent in patients with
      OSAS before nasal CPAP treatment, and tended to increase during the treatment.

PMID- 10202317
TI  - Hemodynamic effects of bilevel nasal positive airway pressure ventilation in
      patients with heart failure.
AB  - AIMS: Benefits of nasal continuous positive airway pressure (CPAP) in patients
      presenting with chronic heart failure (CHF) are controversial. The purpose of
      this study was to compare the hemodynamic effects of CPAP and bilevel positive
      airway pressure (BiPAP) in patients with or without CHF. METHODS AND RESULTS:
      Twenty patients with CHF and 7 with normal left ventricular function underwent
      cardiac catheterization. Measurements were made before and after three 20-min
      periods of BiPAP: expiratory positive airway pressure (EPAP) = 8 cm H2O and
      inspiratory positive airway pressure (IPAP) = 12 cm H2O, EPAP = 10 cm H2O and
      IPAP = 15 cm H2O, and CPAP = EPAP = IPAP = 10 cm H2O administered in random
      order. Positive pressure ventilation decreased cardiac output (CO) and stroke
      volume. No change was observed in either pulmonary or systemic arterial pressure.
      There was no difference in the hemodynamic effects of the three ventilation
      settings. Only mean pulmonary wedge pressure (MPWP) and heart rate were lower
      with CPAP than with BiPAP. CO decreased only in patients with low MPWP (</=12 mm
      Hg). BiPAP ventilation increased PaO2 and decreased PaCO2 more than CPAP.
      CONCLUSIONS: In patients with cardiac failure, a decrease in CO occurs both
      during CPAP and BiPAP, when pulmonary wedge pressure is low (</=12 mm Hg).

PMID- 10202318
TI  - Contribution of lung function to exercise capacity in patients with chronic heart
      failure.
AB  - BACKGROUND: The importance of exercise capacity as an indicator of prognosis in
      patients with heart disease is well recognized. However, factors contributing to
      exercise limitation in such patients have not been fully characterized and in
      particular, the role of lung function in determining exercise capacity has not
      been extensively investigated. OBJECTIVE: To examine the extent to which
      pulmonary function and respiratory muscle strength indices predict exercise
      performance in patients with moderate to severe heart failure. METHODS: Fifty
      stable heart failure patients underwent a maximal symptom-limited cardiopulmonary
      exercise test on a treadmill to determine maximum oxygen consumption (VO2max),
      pulmonary function tests and maximum inspiratory (PImax) and expiratory (PEmax)
      pressure measurement. RESULTS: In univariate analysis, VO2max correlated with
      forced vital capacity (r = 0.35, p = 0.01), forced expiratory volume in 1 s (r =
      0.45, p = 0.001), FEV1/FVC ratio (r = 0.37, p = 0.009), maximal midexpiratory
      flow rate (FEF25-75, r = 0. 47, p < 0.001), and PImax (r = 0.46, p = 0.001), but
      not with total lung capacity, diffusion capacity or PEmax. In stepwise linear
      regression analysis, FEF25-75 and PImax were shown to be independently related to
      VO2max, with a combined r and r2 value of 0. 56 and 0.32, respectively.
      CONCLUSIONS: Lung function indices overall accounted for only approximately 30%
      of the variance in maximum exercise capacity observed in heart failure patients.
      The mechanism(s) by which these variables could set exercise limitation in heart
      failure awaits further investigation.

PMID- 10202319
TI  - Diagnostic value of endoscopic ultrasonography-guided fine-needle aspiration
      cytology of mediastinal masses in patients with intrapulmonary lesions and
      nondiagnostic bronchoscopy.
AB  - Several procedures are available for the cytopathological diagnosis of
      mediastinal lesions. The purpose of this study was to evaluate the diagnostic
      value of endoscopic ultrasonography (EUS)-guided fine-needle aspiration (FNA) in
      patients with mediastinal mass lesions/lymph node enlargement. All patients had
      intrapulmonary lesions on chest X ray and/or CT scan, and inconclusive findings
      by endobronchial forceps biopsy and/or brush cytology. EUS-guided FNA was
      performed in 16 patients using a modified oblique forward-viewing gastroscope
      with an electronic multielement curved linear ultrasound transducer. After the
      region of interest was localized, a 22-gauge Vilmann-Hancke needle was introduced
      via the 2-mm biopsy channel. The cytological diagnosis of EUS-guided FNA was
      conclusive for cancer in 9 patients and in the other 7 patients the aspirated
      samples revealed a benign lesion. In 10 patients the final diagnosis was cancer,
      thus EUS-guided FNA was diagnostic for malignancy in all but 1 of the lesions
      (sensitivity 90.0%). In 1 patient epitheloid cell granuloma was detected by
      cytological examination of the FNA. Following tuberculostatic treatment the
      lesions disappeared completely on CT scan and EUS. The overall accuracy in this
      study amounted to 93.7%. From this and other studies discussed, it is assumed
      that the procedure is an accurate and safe technique to examine nodular lesions
      suggestive of metastatic lymph node involvement.

PMID- 10202320
TI  - Subchronic exposure to diisocyanates increases guinea pig tracheal smooth muscle
      responses to acetylcholine.
AB  - OBJECTIVE: In order to study the threshold concentrations of isocyanates (IC) for
      induction of lung disorders, constrictive responses of tracheal smooth muscles to
      acetylcholine (ACH) in guinea pigs with and without diisocyanate [toluene
      diisocyanate (TDI), hexamethylene diisocyanate (HDI) and diphenylmethane
      diisocyanate (MDI)] exposure were investigated. METHODS: An IC-induced increase
      in smooth muscle responsiveness was studied by measuring cumulative ACH dose
      responses (10(-10) to 10(-4) M ACH). Basal ACH dose-response curves, measured
      twice in intervals of 1 h using tracheal preparations of 11 guinea pigs
      previously not exposed to IC, were reproducible. RESULTS: Subchronic in vivo
      exposures to TDI, HDI, and MDI atmospheres of 10 and 20 parts per billion (ppb)
      on 5 consecutive days led to significantly (p < 0.05) increased ACH
      responsiveness of tracheal smooth muscle, whereas concentrations of 2.5 and 5 ppb
      were not effective. Exposure to HDI atmospheres of 10 ppb for 1, 2, 4, or 8 weeks
      resulted in a time-dependent increase in ACH responses (p < 0.05) of guinea pig
      tracheal smooth muscle. Increased tracheal muscle responses to ACH were transient
      since tracheal preparations from animals exposed to 10 and 20 ppb MDI for 4 weeks
      and with an exposure-free interval of 8 weeks before preparation did not show
      enlarged ACH responses, which were present in preparations at the end of the
      exposure period (p < 0.05). Exposure to low IC concentrations as present in
      workplaces cause increased ACH responsiveness of guinea pig tracheal smooth
      muscle. The increased responsiveness of the airways seems to be largely
      reversible, since normal responses were found after 8 weeks of IC avoidance.
      CONCLUSION: Reversibility of IC-induced airway hyperresponsiveness is of great
      occupational and preventive medical importance. Workers with acquired airway
      hyperresponsiveness might escape lung damage if the changes are detected in an
      early stage before alterations in lung function are in a chronic stage.

PMID- 10202321
TI  - An unusual cause of a persistent pulmonary infiltrate and weight loss.

PMID- 10202322
TI  - Forced expiratory wheezes in a patient with dynamic expiratory narrowing of
      central airways and an oscillating pattern of the flow-volume curve.
AB  - Forced expiratory wheezes (FEW) are common and the pathogenesis of this
      phenomenon might involve fluttering of the airways, but this theory has not been
      confirmed in patients. We report a case of a patient with FEW and a normal FEV1
      that showed a bronchoscopically confirmed collapse of the trachea and main stem
      bronchi during forced expiration. Superimposed to the flow-volume curve was an
      oscillating pattern with a frequency that corresponded well with the wheeze
      generated during forced expiration. The oscillating pattern in the flow-volume
      curve and the collapse of the major airways supports the theory of wheezes
      generated by fluttering airways during forced expiration. Although FEW may be
      found also in healthy subjects, flow limitation is essential for the generation
      of FEW. The inclusion of a forced expiratory maneuver in the clinical examination
      might therefore be helpful in guiding the diagnosis towards airways obstruction.

PMID- 10202323
TI  - Invasive thymoma with long-term survival by extensive reoperation.
AB  - The recurrence of invasive thymoma is often observed; however, no accepted
      treatment of recurrent invasive thymoma has yet been established. We herein
      report a 41-year-old woman with invasive thymoma and pleural dissemination who
      demonstrated long-term survival after undergoing 4 operations. Based on our
      findings, reoperation is thus suggested in patients with intrathoracic recurrence
      and long-term survival can be expected.

PMID- 10202324
TI  - A man with a prosthetic ear and multiple pulmonary nodules.
AB  - Basal cell carcinoma is generally regarded as a relatively indolent tumor easily
      controlled with local therapy. When neglected or inadequately treated this tumor
      can become locally aggressive and in rare circumstances metastasize. This report
      documents a case of basal cell carcinoma metastatic to the lung that resulted in
      rapidly progressive respiratory failure and death.

PMID- 10202325
TI  - Pulmonary alveolar proteinosis in a patient with chronic myelogenous leukemia.
AB  - We describe the case of a 53-year-old Philadelphia-chromosome-positive woman with
      chronic myelogenous leukemia, who developed pulmonary alveolar proteinosis (PAP).
      The possible mechanism involved in the pathogenesis of PAP are discussed based on
      the clinical and laboratory data for this patient as well as on experimental and
      clinical data reported in the literature.

PMID- 10202326
TI  - Bilateral hemothorax revealing mediastinal parathyroid adenoma.
AB  - We report the case of a 63-year-old woman admitted to hospital because of
      bilateral hemothorax associated with acute respiratory failure and laterotracheal
      neoformation. A right thoracoscopy biopsy revealed a paratracheal parathyroid
      adenoma which was responsible for bilateral hemothorax and primary
      hyperparathyroidism. A curative resection was successfully performed by
      cervicotomy.

PMID- 10202327
TI  - Acute abdominal pain in a lung transplant recipient. Diagnosis: Acute
      appendicitis in the presence of a pin.

PMID- 10202328
TI  - A chest wall restrictor to study effects on pulmonary function and exercise. 1.
      Development and validation.
AB  - Chest wall-restrictive loading reduces a person's ability to expand the chest
      wall during inhalation and results in decrements in lung capacities, resting
      pulmonary function, and ultimately, exercise performance. Chest wall restriction
      is observed in some forms of skeletal and pulmonary diseases (e.g., scoliosis) as
      well as in occupational situations (e.g., bulletproof vests). We have designed a
      constant-pressure chest wall-restrictive device that provides a quantifiable and
      reproducible load on the chest. This paper describes the device and the initial
      pulmonary function tests conducted. Ten subjects participated in this study.
      Subjects wore the restrictive device while performing pulmonary function tests at
      four externally added restrictive loads on three separate occasions. A two-way
      repeated-measures multivariate analysis of variance revealed significant
      decreases in forced expiratory vital capacity (FVC) and forced expiratory volume
      in 1 s (FEV1.0) at each load while the ratio of FEV1.0 to FVC (FEV1.0%) was
      maintained. No significant differences in any variable were found across time or
      between the seated and standing position. These results indicate that this chest
      wall-restrictive device provides a quantifiable added inspiratory load in the
      breathing cycle that results in reproducible decrements in pulmonary function
      representative of those seen in some restrictive pulmonary disease and
      occupational situations.

PMID- 10202329
TI  - A chest wall restrictor to study effects on pulmonary function and exercise. 2.
      The energetics of restrictive breathing.
AB  - Chest wall restriction, whether caused by disease or mechanical constraints such
      as protective outerwear, can cause decrements in pulmonary function and exercise
      capacity. However, the study of the oxygen cost associated with mechanical chest
      restriction has so far been purely qualitative. The previous paper in this series
      described a device to impose external chest wall restriction, its effects on
      forced spirometric volumes, and its test-retest reliability. The purpose of this
      experiment was to measure the oxygen cost associated with varied levels of
      external chest wall restriction. Oxygen uptake and electromyogram (EMG) of the
      external intercostals were recorded during chest restriction in 10 healthy males.
      Subjects rested for 9 min before undergoing volitional isocapnic hyperpnea for 6
      min. Subjects breathed at minute ventilations (V.I) of 30, 60, and 90 liters/min
      with chest wall loads of 0, 25, 50 and 75 mm Hg applied. Frequency of breathing
      was set at 15, 30, and 45 breaths per minute with a constant tidal volume (VT) of
      2 liters. Oxygen uptake was measured continuously at rest and throughout the
      hyperventilation bouts, while controlling V.I and VT. Integrated EMG (IEMG) from
      the 3rd intercostal space was recorded during each minute of rest and
      hyperventilation. Two-way ANOVA with repeated measures revealed that chest wall
      loading and hyperpnea significantly increased V.O2 values (p < 0.01). External
      intercostal IEMG levels were significantly increased (p < 0.05) at higher
      restrictive load (50 and 75 mm Hg) and at the highest minute ventilation (90
      liters/min). These data suggest that there is a significant and quantifiable
      increase in the oxygen cost associated with external chest wall restriction which
      is directly related to the level of chest wall restriction.

PMID- 10202330
TI  - Pleural metastasis of a squamous cell carcinoma of the gingiva.

PMID- 10202331
TI  - Seasonal variations in vitamin-D status and the incidence of tuberculosis in
      different countries.

PMID- 10202332
TI  - Chemokines and IL-5: major players of eosinophil recruitment in asthma.

PMID- 10202333
TI  - Obesity and asthma: cause for concern?

PMID- 10202334
TI  - Do inhaled corticosteroids reduce serum IgE levels? The answer is maybe but how
      relevant is the question?

PMID- 10202335
TI  - Artificial ventilation-acquired sinopathy in the critically ill - the maxillary
      sinuses revisited.

PMID- 10202336
TI  - Biosynthesis of cysteinyl-leucotrienes in aspirin-intolerant asthma.

PMID- 10202337
TI  - The role of interleukin-5, interleukin-8 and RANTES in the chemotactic attraction
      of eosinophils to the allergic lung.
AB  - BACKGROUND: Bronchoalveolar lavage (BAL) fluid from patients with birch-pollen
      allergy lavaged during the season showed an elevated chemotactic activity for
      eosinophils compared with BAL fluid from the same patients before the start of
      the season. AIM: The aim of this study was to identify the eosinophil chemotactic
      agents in the BAL fluid, to compare these findings with in vitro studies on
      selected cytokines, and to investigate the interactions between these cytokines.
      METHODS: Neutralizing antibodies for interleukins (IL) -2, -5 and -8, RANTES and
      leukaemia inhibitory factor (LIF) were added to the BAL fluid, and the
      chemotactic activity was tested with eosinophils from allergic donors.
      Eosinophils from healthy donors were preincubated with IL-5 in order to mimic the
      primed state of eosinophils from allergics, and the migration towards recombinant
      IL-5, IL-8, and RANTES in different combinations was measured. Eosinophils from
      allergic donors were also used. RESULTS: Anti-IL-5, anti-IL-8 and anti-RANTES
      inhibited the chemotactic activity in the BAL fluid. Recombinant RANTES induced
      migration, which was enhanced by preincubation of the cells with IL-5. Only
      eosinophils from symptomatic allergics responded to IL-8, and IL-5 was not
      sufficient to prime normal eosinophils in vitro to an IL-8 response. A negative
      correlation was found between the level of in vivo activation of the cells and
      their response to IL-5, and a positive correlation with the response to RANTES.
      CONCLUSION: IL-8 and RANTES are important for eosinophil accumulation to the lung
      of pollen-allergic asthmatics. IL-5 alone may not be responsible for the priming
      of eosinophils in vivo, but is an essential cofactor for the other
      chemoattractants.

PMID- 10202338
TI  - Association between body mass index and allergy in teenage girls in Taiwan.
AB  - BACKGROUND: The prevalence of atopy and asthma is affected by age, sex and
      lifestyle factors. Obesity was reported to be a risk factor for asthmatic
      symptoms in children and adults. OBJECTIVE: To examine the relation between body
      mass index (BMI) and the prevalence of atopy, rhinitis, wheezing and bronchial
      responsiveness in adolescents. METHODS: BMI (kg/m2), skin-prick test, bronchial
      hyperresponsiveness (BHR) to methacholine, and self-reported rhinitis and airway
      symptoms were assessed in a cross-sectional survey in 1459 eighth-grade students
      (age 13.2 to 15.5, mean 13.6 years) of seven junior high schools in northern
      Taiwan. RESULTS: The prevalence of atopy was 42% in boys and 27% in girls. The
      study population was grouped into quintiles of BMI by sex. Girls in the highest
      BMI quintile had higher prevalence of atopy and rhinitis symptoms. Compared with
      the middle three quintiles, they had increased risk of atopy in multivariate
      analyses adjusted for area of living, sibling number, parent education level and
      family history of asthma (odds ratio = 1.77, 95% confidence interval = 1.15
      2.73). Girls with the lowest BMI quintile had lower prevalence of BHR and
      wheezing. Compared with the middle three quintiles, they had reduced risk of BHR
      in multivariate analyses adjusted for area of living, atopy, family history of
      asthma, and baseline pulmonary function (odds ratio = 0.40, 95% confidence
      interval = 0.20-0.81). No association between BMI and atopy or BHR was seen in
      boys. CONCLUSION: BMI was a significant predictor of atopy, allergic symptoms and
      BHR in teenage girls.

PMID- 10202339
TI  - The relationship between anthropometric measurements at birth: asthma and atopy
      in childhood.
AB  - BACKGROUND: Recent studies have reported that a large head circumference at birth
      is associated with an increased risk of raised serum IgE in adult life, and
      asthma during childhood. OBJECTIVE: To examine the relationship between head
      circumference and other anthropometric measurements at birth and asthma and
      indices of atopy in childhood. METHODS: The presence of asthma and measures of
      atopic status (total serum IgE level and skin prick tests to common allergens)
      were assessed prospectively in offspring of families participating in a community
      based genetic study in Southampton, UK. Measures of perinatal variables including
      birth weight, head circumference at birth, and gestational age were obtained from
      hospital records of 239 offspring aged 6-23 years. RESULTS: Children with a head
      circumference of 37 cm or more at birth had a relative risk of an elevated serum
      total IgE (> 150 IU) of 3.2 (95% CI 1.0-10.4). There were no consistent
      relationships between head circumference at birth and either skin prick
      positivity or the development of clinical asthma. There was no significant
      association between other perinatal markers and measures of atopic status or
      clinical asthma. CONCLUSION: The study has identified that a large head
      circumference at birth is associated with an increased risk of an elevated total
      serum IgE in childhood. The reasons for this association, and the lack of an
      association with asthma are unclear and will require further research.

PMID- 10202340
TI  - Head circumference at birth and maternal factors related to cord blood total IgE.
AB  - BACKGROUND: A recent study reported an association between a large head
      circumference at birth and adult total IgE. However, no study has yet looked at
      the relation between head circumference and cord blood IgE. OBJECTIVES: To assess
      the relationship between child's cord blood total IgE and head circumference at
      birth taking parental allergy and smoking habits as well as placental
      calcifications into account. METHODS: Two samples of unselected newborns and
      their mothers with uncomplicated pregnancies were studied: 235 in study A with
      data on parental allergy and 99 in study B with data on placental calcifications.
      RESULTS: In both studies, cord blood IgE was significantly related to large head
      circumference at birth (0.07 vs 0.15 IU/mL for newborns < 37 cm vs >/= 37 cm,
      respectively, P = 0. 03 for study A and 0.09 vs 0.28 IU/mL, P = 0.04 for study
      B). Cord blood IgE was unrelated to parental smoking habits. Maternal IgE
      significantly increased in mothers exposed to both active and passive smoking
      during pregnancy compared with other pregnant women. High cord blood IgE were
      associated with high maternal IgE (r = 0. 38; P < 0.001). Multiple linear
      regression showed that large head circumference, maternal IgE and clinical
      manifestations of maternal, but not paternal, allergy were independently related
      to cord blood IgE (study A). Large head circumference and placental
      calcifications were independently related to a higher cord blood IgE level (study
      B). CONCLUSIONS: Besides the role of genetic factors, results on the preferential
      role of maternal vs paternal allergy and associations to large head circumference
      and placental calcifications support the hypothesis of the role of environmental
      factors during pregnancy on the level of cord blood IgE.

PMID- 10202341
TI  - The intestinal microflora in allergic Estonian and Swedish 2-year-old children.
AB  - BACKGROUND: The prevalence of allergic diseases seems to have increased
      particularly over the past 35-40 years. Furthermore, allergic disease is less
      common among children in the formerly socialist countries of central and Eastern
      Europe as compared with Western Europe. It has been suggested that a reduced
      microbial stimulation during infancy and early childhood would result in a slower
      postnatal maturation of the immune system and development of an optimal balance
      between TH1- and TH2-like immunity. AIMS: To test the hypothesis that allergic
      disease among children may be associated with differences in their intestinal
      microflora in two countries with a low (Estonia) and a high (Sweden) prevalence
      of allergy. METHODS: From a prospective study of the development of allergy in
      relation to environmental factors, 29 Estonian and 33 Swedish 2-year-old children
      were selected. They were either nonallergic (n = 36) or had a confirmed diagnosis
      of allergy (n = 27) as verified by typical history and at least one positive skin
      prick test to egg or cow's milk. Weighed samples of faeces were serially diluted
      (10-2-10-9) and grown under anaerobic conditions. The counts of the various
      genera and species were calculated for each child. In addition, the relative
      amounts of the particular microbes were expressed as a proportion of the total
      count. RESULTS: The allergic children in Estonia and Sweden were less often
      colonized with lactobacilli (P < 0.01), as compared with the nonallergic children
      in the two countries. In contrast, the allergic children harboured higher counts
      of aerobic micro-organisms (P < 0. 05), particularly coliforms (P < 0.01) and
      Staphylococcus aureus (P < 0.05). The proportions of aerobic bacteria of the
      intestinal flora were also higher in the allergic children (P < 0.05), while the
      opposite was true for anaerobes (P < 0.05). Similarly, in the allergic children
      the proportions of coliforms were higher (P < 0. 05) and bacteroides lower (P <
      0.05) than in the nonallergic children. CONCLUSIONS: Differences in the
      indigenous intestinal flora might affect the development and priming of the
      immune system in early childhood, similar to what has been shown in rodents. The
      role of intestinal microflora in relation to the development of infant immunity
      and the possible consequences for allergic diseases later in life requires
      further study, particularly as it would be readily available for intervention as
      a means for primary prevention of allergy by the administration of probiotic
      bacteria.

PMID- 10202342
TI  - Regional variations in grass pollen seasons in the UK, long-term trends and
      forecast models.
AB  - BACKGROUND: Three sites in the UK have daily records of pollen spanning several
      decades, giving the longest data sets worldwide. Previous research on London data
      revealed decreasing severity of grass pollen seasons. This is often taken as a
      model for the whole country but comparisons with Derby and Cardiff, in different
      regions of local climate and land-use, emphasize the need for regional studies.
      OBJECTIVE: The grass pollen seasons were analysed for three contrasting long-term
      sites to provide regional insight into the changing incidence of hay fever.
      METHODS: Pollen was monitored by volumetric instruments using standard
      techniques. Data have been taken from 1961 to 1993 to examine variation in grass
      pollen seasons in relation to land-use changes, cumulative temperatures and
      rainfall. Models were developed to predict total seasonal catches. RESULTS: At
      Cardiff the annual counts and severity increased in the 1960s, declined in the
      1970s and rose again in the 1980s. At Derby and London the annual counts and
      severity declined but at different rates. Start dates have tended to become
      earlier at Cardiff and Derby, but later at London. Trends in annual counts and
      severity are similar to changes in grassland areas but they cannot be accounted
      for entirely by these. Weather in spring and early summer has tended to become
      warmer but there are no sustained patterns in June and July. No trends are
      apparent in the rainfall records for these months. The maximum explanation (r2
      >/= 95%) in forecast models was obtained using 10-day aggregates of weather.
      CONCLUSION: The contrasting patterns both in the pollen records and land-use
      changes between the three sites emphasize the need for regional data. The
      predictive models achieved a high degree of explanation enabling pollen season
      severity to be forecast with high confidence shortly before the start date.

PMID- 10202343
TI  - Effects of inhaled beclomethasone dipropionate on serum IgE levels and clinical
      symptoms in atopic asthma.
AB  - BACKGROUND: A high serum immunoglobulin (Ig)E level is considered a potent
      predictor for the development of asthma and IgE is targeted for treatment of
      asthma. Although inhaled corticosteroids are well established in the treatment of
      asthma, the effects of inhaled corticosteroids on serum IgE levels in asthma
      remain uncertain. METHODS: We therefore examined asthma symptoms, concentrations
      of total serum IgE and specific IgE antibodies to selected allergens, blood
      eosinophil counts and lung functions before and 3 months after treatment with
      either inhaled beclomethasone dipropionate (BDP; 800 microg/day) (n = 7) or
      inhaled beta2-agonists alone (n = 7) in patients with atopic asthma in a
      randomized, double-blind, parallel-group controlled trial. RESULTS: Inhaled BDP
      significantly improved asthma symptom scores and forced expiratory volume in 1 s,
      and decreased blood eosinophil counts, total serum IgE levels and specific IgE
      antibodies to house dust mite and cedar. Decreases in total serum IgE
      significantly correlated with an improvement in asthma symptom scores. In
      contrast, none of parameters altered in patients with atopic asthma treated with
      inhaled beta2-agonists alone. CONCLUSIONS: Inhaled corticosteroids may improve
      the subsequent clinical course of atopic asthma in association with a reduction
      of serum IgE levels.

PMID- 10202344
TI  - Inflammatory mediators in bronchoalveolar lavage samples from children with and
      without asthma.
AB  - BACKGROUND: We investigated whether eosinophils and mast cells, found in the
      airways of children with wheeze, were activated during relatively asymptomatic
      periods. METHODS: A nonbronchoscopic bronchoalveolar lavage (BAL) procedure was
      performed on children presenting for an elective surgical procedure. Eosinophil
      derived (eosinophil cationic protein, ECP) and mast cell-derived
      (histamine/tryptase) mediator concentrations were measured in the BAL fluid. A
      detailed history and serum immunoglobulin E were used to classify the children
      into four groups: atopic with and without asthma, viral-associated wheeze and
      normal controls. RESULTS: The ECP concentrations in BAL from atopic asthmatic
      subjects were significantly higher than those measured in BAL from normal
      controls (P < 0.01), no other groups differed significantly. Histamine
      concentrations were elevated in both the atopic asthmatic and viral-associated
      wheeze groups compared with controls (P < 0.02) and additionally higher
      concentrations were obtained in atopics with asthma compared with atopics without
      asthma (P < 0.03). Tryptase concentrations did not differ between groups,
      although the tryptase and histamine concentrations correlated significantly (r =
      0.78, P < 0.0001). CONCLUSIONS: Elevated histamine concentrations were found in
      children with wheeze regardless of the aetiology, whereas ECP was only elevated
      in those asthmatics with atopy. This suggests that even in relatively quiescent
      periods, there is some on going activation of airway eosinophils in children with
      atopic asthma.

PMID- 10202345
TI  - Norm values for eosinophil cationic protein in nasal secretions: influence of
      specimen collection.
AB  - BACKGROUND: Eosinophil granulocytes play an important role in allergic
      inflammation of the nasal mucosa. Eosinophil cationic protein (ECP) is a specific
      eosinophil granule protein released upon activation of these cells. ECP
      concentration in nasal secretions has been demonstrated to be a good marker for
      the activity of eosinophilic nasal mucosal inflammation. The clinical use of such
      a marker requires defined values which are regarded as pathological or within
      normal range. In analyses of nasal secretion samples, the sampling method has an
      important influence on the data obtained. OBJECTIVE: We investigated ECP levels
      in nasal secretions (NS) of healthy volunteers obtained by seven different
      methods of sample collection to define norm values and to evaluate the clinical
      use of the different methods. METHODS: A total of 839 healthy individuals were
      evaluated using blowing the nose (Bl: n = 82), suction (Suc: n = 69), Okuda
      microsuction technique (MSuc: n = 93), absorbent cotton wool samplers (CWS: n =
      156), rubber-foam samplers (RFS: n = 193), nasal lavage (Lav: n = 112) and nasal
      spray washing (NSW: n = 134). RESULTS: Missing values occurred in more than 60%
      in Bl, Suc and MSuc, so that no norm range was defined for these methods. Norm
      range for ECP in NS was 5-46 ng/mL for CWS, 7-41 ng/mL for RFS, 4-51 ng/mL for
      NSW, and 3-31 ng/mL for Lav. CONCLUSIONS: When comparing seven different methods
      used in this study to collect nasal secretions and determine ECP levels, the
      method based upon absorption or nasal washing was the best.

PMID- 10202346
TI  - Reference values of total serum IgE and their significance in the diagnosis of
      allergy among the young adult Kuwaiti population.
AB  - BACKGROUND: The reference total serum immunoglobulin (IgE) values and the
      usefulness of total IgE values in the diagnosis of allergy have not been
      established for the Kuwaiti population. The literature reference values may not
      be applicable since such values often vary among ethnic nationalities. OBJECTIVE:
      The aim of this study was to establish the reference IgE values for the young
      adult Kuwaiti population and to determine the usefulness of such values in the
      diagnosis of allergic diseases in the community. METHODS: A total of 1057
      randomly selected young adults were screened for atopy using the Pharmacia CAP
      PhadiatopR method. Atopy was detected in 423 individuals (40.0%). Total serum IgE
      was then measured in 542 randomly selected Phadiatop-negative (non-atopic) cases
      in the age range 18-50 years (mean 28.9 years) and male:female ratio of 1.3.
      RESULTS: Serum total IgE values in non-atopics covered a very wide range (< 2
      1993 kU/L) with a geometric mean (GM) value of 43.7 kU/L. The reference range,
      calculated as the 95% confidence interval of the log IgE (95% CI) was 3.2-602.5
      kU/L. The 90% CI was 11.7-162 kU/L. The GM was significantly higher for males
      than females, (53.7 vs. 35.5 kU/L, P < 0.001) and for smokers than non-smokers,
      (64.6 vs. 40.7 kU/L, P < 0.01), but was independent of age. Although the GM for
      the non-atopics (43.7 kU/L) was significantly lower than those of the
      asymptomatic atopics (213.8 kU/L) and allergic asthmatics (626.6 kU/L), the 95%
      CI for the three groups showed considerable overlap. CONCLUSIONS: These results
      show that the normal total IgE values in the young adult Kuwaiti population are
      generally high and that the distribution of the values is so wide that the
      diagnostic value of total serum IgE in this community is likely to be very
      limited.

PMID- 10202347
TI  - Cord blood leucocytes/basophils produce and release sulfidoleucotrienes in
      response to allergen stimulation.
AB  - BACKGROUND: Leucocyte-derived sulfidoleucotrienes (SLT) from children and adults
      can be detected in vitro in response to specific allergen stimulation, a
      mechanism thought to require the presence of allergen-specific immunoglobulin
      (Ig)E antibodies on the surface of basophils. It is unknown whether this
      mechanism is functional in cord blood basophils. OBJECTIVE: We studied the in
      vitro SLT-release of leucocytes in response to allergen and anti-IgE stimulation
      in term newborns and children with allergic diseases. METHODS: Cord blood from
      randomly selected term newborns were analysed for total IgE-antibodies and in
      vitro SLT-release in response to allergen and anti-IgE stimulation. Children from
      an allergy outpatient clinic were used as the control group. The Cellular
      Allergen Stimulation Test (CAST) was used as read-out system. Allergen
      stimulation was performed with an allergen-mix containing 21 nutritive and
      inhalant allergens. RESULTS: Peripheral blood leucocytes/basophils derived from
      allergic children (n = 56; median SLT release 1049 pg/mL) were more responsive to
      anti-IgE stimulation as cord blood leucocytes/basophils (n = 104; median 419
      pg/mL P < 0.0001). In response to stimulation with an allergen-mix, the two
      groups did not differ significantly from each other. Only SLT-releasability in
      response to anti-IgE showed a correlation with cord blood IgE. CONCLUSIONS:
      Sulfidoleucotriene-release of cord blood basophils is functional in response to
      allergens. It appears possible that cord blood basophils are armed with allergen
      specific IgE-antibodies though not detectable in serum. Therefore, cord blood SLT
      release may indirectly reflect prenatal priming with allergens with subsequent
      production of allergen-specific IgE.

PMID- 10202348
TI  - Increased positivity of skin test and allergenic stability of glycerinated
      soybean hull extracts.
AB  - BACKGROUND: Results obtained from previous experiences with soybean hull antigens
      suggest that the addition of glycerine to the extract increases positivity of the
      skin test. OBJECTIVE: The purpose of this study was to investigate the effect of
      this glycerine addition and the influence of different storage temperatures on
      the potency of soybean hull extracts. METHODS: Twenty-two asthmatic patients
      admitted to emergency rooms during one of the soybean-related Barcelona asthma
      epidemics were evaluated 2 years after the last epidemic for: (1) sensitivity to
      prick test with glycerinated and non-glycerinated extracts, both fresh and stored
      at 4 degrees C, - 20 degrees C and - 70 degrees C for 30 days, and (2) specific
      IgE to a fresh hull extract. All extracts were also studied by sodium dodecyl
      sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). RESULTS: No differences
      in positivities were detected for prick tests performed the same day of
      preparation between non-glycerinated (5/22; 22.7%) and glycerinated (4/22; 18.2%)
      extracts. After 30 days storage, positivities of prick test with non-glycerinated
      extracts stored at 4 degrees C did not significantly differ from the results
      obtained on the first day. However, prick tests performed with glycerinated
      extracts stored for 30 days showed increased positivity for the extracts stored
      at 4 degrees C (7/22; 31%) (P < 0.05) as well as for those stored at - 20 degrees
      C and - 70 degrees C (9/22; 40.9%) (P < 0.001). This latter percentage is similar
      to that of specific immunoglobulin E detected by radioimmunoassay (10/22; 45.
      4%). Also, for the glycerinated extracts only, the quantitative response showed
      an increase in mean diameter of the induration at 30 days at the three
      temperatures, even though owing to the great standard deviation and limited
      number of patients, it was only significant for the extract stored at - 20
      degrees C (P < 0.01). SDS-PAGE gel densitometry at 30 days demonstrated a loss of
      protein in the bands with a molecular weight higher than 66.2 kDa for non
      glycerinated extracts stored at 4 degrees C. CONCLUSIONS: The results of this
      study confirm previous observations with soybean hull allergen extracts and
      indicate that (1) storage of soybean hull extracts with glycerine addition for 30
      days at the concentration studied (1:100 w/v) determines a significant increase
      in the positivity of skin tests, and (2) glycerine addition stabilizes soybean
      hull extracts at any of the temperatures studied.

PMID- 10202349
TI  - IgE and T-cell responses to high-molecular weight allergens from bee venom.
AB  - BACKGROUND: Bee venom contains multiple allergens with a wide distribution of
      molecular weight. In contrast with conventional bee venom desensitization,
      peptide or recombinant allergen immunotherapy may have to take into account
      patients' individual patterns of humoral or cellular response. OBJECTIVE: To
      study immunoglobulin (Ig)E and T-cell responses to high-molecular weight bee
      venom allergens >/= 50 kDa. METHODS: Bee venom proteins were separated by size
      exclusion chromatography and fractions were characterized by one and two
      dimensional gel electrophoresis. IgE antibody binding to bee venom fractions was
      analysed by immunoblotting and T-cell responses by proliferation assay. RESULTS:
      Among 38 bee venom-hypersensitive patients, IgE recognition pattern of bee venom
      allergens varied greatly. IgE bound mainly to phospholipase A2 and furthermore to
      several proteins >/= 50 kDa (50, 54, 69, 84 and 94 kDa). N-terminal sequences of
      these proteins showed no homology with known proteins. In addition, peripheral
      mononuclear cells from patients as well as from nonatopic donors strongly
      proliferated in response to those proteins. CONCLUSIONS: Although present in low
      amounts, high-molecular weight allergens from bee venom elicit strong IgE and T
      cell responses, and may need to be considered as clinically relevant. Therefore,
      the development of peptide or recombinant protein-based immunotherapy for bee
      venom allergy may require careful characterization of such allergens.

PMID- 10202350
TI  - Carob is not allergenic in peanut-allergic subjects.
AB  - BACKGROUND: The antigenic potential of proteins from the carob bean, a member of
      the legume family used as a food additive, have not so far been investigated and
      legumes share antigenic proteins with peanut, a potent trigger of anaphylaxis.
      OBJECTIVE: To assess the carob protein determinants of sensitization in peanut
      allergic children. METHODS: In a prospective, double-blind, placebo-controlled
      study 12 patients (median age 9.5 years) with a history of hyperreactivity to
      peanut (anaphylaxis) were assessed. Skin prick tests with a commercial peanut
      allergen, raw carob pulp, raw and cooked carob cotyledon formula were used to
      confirm the history. RAST for peanuts and cooked carob were used to evaluate
      sensitization to these proteins. Carob-specific IgE were identified by
      immunoblotting analyses. Allergic reactivity was evaluated during double-blind
      placebo-controlled food challenges (DBPCFC; 5.5 g carob extract and cooked carob
      cotyledon formula). RESULTS: Peanut allergen-induced skin prick test positivity
      in all children (confirmed during double-blinded challenge in 6/12 patients),
      carob pulp in 3/12 patients, raw carob bean in 6/12, and cooked carob cotyledon
      formula in none. RAST were positive for peanut in all cases but negative for
      carob beans in 9/12 cases. Immunoblot analyses found peanut-specific IgE in all
      cases and raw carob bean-specific IgE in eight cases. Carob allergens were
      identified in the 17.5, 48, and 66 kDa MW bands. The least allergenic density was
      found for cooked carob proteins. There was no clinical reactivity with either raw
      or cooked carob during DBPCFC. CONCLUSIONS: These data suggest that carob
      specific sensitization, apparent both in vitro and in SPTs, can be concordant
      with peanut allergy and that cooked carob can be ingested by children who are
      allergic to peanuts. That heat-processing deactivates carob protein allergenicity
      has dietary implications for polyallergic children.

PMID- 10202351
TI  - Urticaria from beer: an immediate hypersensitivity reaction due to a 10-kDa
      protein derived from barley.
AB  - BACKGROUND: Urticaria from beer has been reported in atopic patients. In these
      subjects, the skin-prick test positivity to and presence of specific serum
      immunoglobulin (Ig)E for barley malt, the basic ingredient used in brewing,
      suggested a type I hypersensitivity to barley component(s). OBJECTIVE: To
      identify the beer allergen(s) and to investigate the presence of related proteins
      in barley. METHODS: Three patients with urticaria from beer and other atopic
      people, some of them suffering from baker's asthma, were examined for both prick
      test sensitivity to and the occurrence of serum-specific IgE for partially
      purified proteins from beer. Allergen identification in beer, malt and barley was
      performed by immunoblotting. RESULTS: Skin-prick tests and detection of specific
      IgE by both solid-phase (RAST) and liquid-phase (AlaSTAT) assays demonstrated
      that the 5-20-kDa beer protein fraction contained the allergen. Immunoblot
      analysis with sera of patients with urticaria from beer showed that IgE bound
      only the 10-kDa protein band in beer and malt, whereas a main 16-kDa protein was
      revealed in barley in addition to a very faint 10-kDa band. With the serum of a
      patient suffering from baker's asthma no IgE binding bands were observed in beer,
      whereas specific IgE binding to several proteins, including a major 16-kDa
      component, were detected for both malt and barley. CONCLUSIONS: Urticaria from
      beer is an IgE-mediated hypersensitivity reaction induced by a protein component
      of approximately 10 kDa deriving from barley. This allergen does not seem to be
      related to the major barley 16-kDa allergen responsible for baker's asthma.
      Because of the severity of the allergic manifestations to beer we recommend
      testing atopic patients positive to malt/barley and/or who exhibit urticarial
      reactions after drinking beer for their sensitivity to this beverage.

PMID- 10202352
TI  - Attenuation of house dust mite Dermatophagoides farinae-induced airway allergic
      responses in mice by dehydroepiandrosterone is correlated with down-regulation of
      TH2 response.
AB  - BACKGROUND: Dehydroepiandrosterone (DHEA), an abundant androgen in circulation,
      has important immunomodulating effects on T-cell differentiation; however, it is
      not known whether this hormone influences allergic responses. OBJECTIVE: We have
      established a murine model of airway inflammation induced by house dust mite
      Dermatophagoides farinae (Der f). Der f challenge of sensitized mice would elicit
      a pulmonary eosinophilic inflammation. In the present study, we employed this
      model system to explore the effect of DHEA on allergic responses. METHODS: Female
      BALB/c mice were fed with a standard diet incorporated with 1.5% (w/w) of DHEA
      for 1 week before sensitization and every other day for an additional 2 weeks
      after sensitization. After intratracheal inoculation of allergen, the Der f
      induced airway inflammation, immunoglobulin (Ig)E antibody production, and
      cytokine expression were compared between control and DHEA-fed mice. RESULTS: In
      control mice the Der f-induced eosinophilia in bronchoalveolar lavage (BAL)
      fluids was accompanied by an increase in production of interleukin (IL)-4, IL-5,
      and interferon IFN-gamma systemically and locally. DHEA supplementation did not
      affect the body weight of mice. However, in mice that were receiving DHEA, the
      numbers of eosinophils and lymphocytes in BAL fluids significantly decreased at
      days 2 and 6 after challenge as compared with control mice. Concomitantly, total
      IgE antibody concentrations as well as IL-4, IL-5, and IFN-gamma levels in BAL
      fluids or serum also significantly reduced. Immunocytochemical staining of BAL
      cells revealed that there were fewer IL-4-, IL-5-, IL-10-, but not IFN-gamma
      positive stained cells in DHEA-fed mice than in mice who consumed unsupplemented
      diet. Reverse transcription-polymerase chain reaction analysis demonstrated DHEA
      decreased the expression of IL-5 and IL-10 transcripts in BAL cells. CONCLUSIONS:
      Our results showed that administration of DHEA during allergic sensitization
      could attenuate the subsequent allergic responses elicited by challenge, and that
      the suppressive effect of DHEA was associated with a down-regulation of TH2
      response.

PMID- 10202353
TI  - Exposure-response relationships for airborne allergens.

PMID- 10202354
TI  - Pillow talk: have we made the wrong beds for our patients to lie in?

PMID- 10202355
TI  - On carpets, construction and covers.

PMID- 10202356
TI  - The treatment of allergic eye disease: has sodium cromoglycate had its day?

PMID- 10202357
TI  - The interaction between the dust mite antigen Der p 1 and cell-signalling
      molecules in amplifying allergic disease.

PMID- 10202358
TI  - Peptidases: structure, function and modulation of peptide-mediated effects in the
      human lung.

PMID- 10202359
TI  - Prevalence of rhinitis, pillow type and past and present ownership of furred
      pets.
AB  - BACKGROUND: There has been no previous work investigating the effects of furred
      pet ownership and pillow type on the risk of developing rhinitis. Recently,
      unexpected and unexplained associations of asthma with nonfeather pillows have
      been reported. OBJECTIVE: We developed a questionnaire-based cross-sectional
      survey to determine whether the past or present ownership of cats or dogs, or the
      use of nonfeather pillows contributes to the development of seasonal or perennial
      rhinitis. METHODS: We surveyed 2555 accompanying friends and relatives of
      patients attending the outpatients departments at one London hospital in 1996.
      Individuals with rhinitis were defined as those suffering with three or more
      symptoms of rhinitis either throughout the year (perennial) or for part of the
      year (seasonal). Present or childhood ownership of cats or dogs was recorded.
      RESULTS: A strong association was seen with nonfeather pillow use and both
      seasonal [odds ratio (OR) 1.85; 95% confidence interval (CI) 1.43-2.5] and
      perennial (OR 2.63; CI 1.67-5. 0) rhinitis. However, more than one-third of
      rhinitics had changed their pillow type. After restricting the data to exclude
      subjects who changed their pillow to avoid allergies, the strong association of
      nonfeather pillow use with perennial rhinitis remained (OR 2.44; CI 1.25-5.0).
      Adjusting the data to the extreme situation where all former pillow type was
      feather changes the apparent risk to 0.99 (CI 0.67-1.43). No associations for
      either seasonal or perennial rhinitis were seen for feather pillows. A weak
      association of current dog ownership is demonstrated for seasonal rhinitis (OR 1.
      47; CI 1.01-2.14). No associations were seen for childhood dog ownership or cat
      ownership at any time with either type of rhinitis. CONCLUSIONS: Feather pillow
      use and the ownership of furred pets appears unlikely to increase the risk of
      developing perennial or seasonal rhinitis. In fact, in contrast with currently
      held views, there is evidence that the use of nonfeather pillows may increase the
      risk.

PMID- 10202360
TI  - Residential characteristics influence Der p 1 levels in homes in Melbourne,
      Australia.
AB  - BACKGROUND: Exposure to house dust mite (HDM) allergens is an important risk
      factor for childhood asthma. Knowledge of environmental determinants of HDM
      allergen levels is essential before designing rational avoidance measures. AIM:
      To investigate the effect of domestic characteristics on HDM allergen (Der p 1)
      levels in Melbourne homes. METHODS: Dust was collected from bed and floor of the
      bedrooms in 485 houses over a period of one year. Dust was analysed for Der p 1
      levels using an enzyme-linked immunosorbent assay. Temperature and relative
      humidity were measured at the visit. Details of residential characteristics were
      collected using a questionnaire. Statistically significant predictors of Der p 1
      levels (P < 0.05) were identified using multiple linear regression. RESULTS: High
      levels of Der p 1 were observed in the floors (geometric mean 17.2 microg/g fine
      dust) as well as in the beds (geometric mean 20.3 microg/g fine dust). Der p 1
      levels in the floor dust were significantly lower in winter and spring. They were
      higher in houses built before 1980 and those with central heating, weather board
      walls, damp bedrooms or fitted old wool carpets. Der p 1 levels in bed dust were
      significantly higher in houses built before 1980, with wooden floors built on
      stumps, with high relative humidity, with visible mould in the room, in beds with
      an old mattress or in beds without a quilt. CONCLUSIONS: We would encourage
      construction of homes without carpets, wooden floors on stumps or weather board
      walls.

PMID- 10202361
TI  - The effects of carpet fresheners and other additives on the behaviour of indoor
      allergen assays.
AB  - BACKGROUND: Chemical agents such as tannic acid and detergents have been shown to
      introduce non-random bias in allergen measurement. OBJECTIVE: We investigated how
      several substances that are commonly found in floor dust (carpet fresheners,
      powdered pesticides, and table salt) affected immunoassays of purified standard
      allergens. METHODS: Three sets of experiments were conducted to: (1) screen for
      interference with allergen enzyme-linked immunosorbent assay (ELISA); (2) test
      for concentration-response; and (3) assess the site-of-action of a given dust
      additive (i.e. the effect on allergen binding to primary or secondary antibody).
      The ELISAs are commercially available two-site monoclonal antibody assays for Der
      p 1, Der f 1, and Fel d 1, and a monoclonal/polyclonal assay for Bla g 1.
      Outcomes are reported in terms of reaction rate (colour change per unit time),
      which is directly proportional to the amount of bound allergen. RESULTS: In the
      initial screening experiments, carpet fresheners tended to decrease Der p 1 assay
      reaction rates, increase Der f 1 assay rates, and produce little change in Fel d
      1 assay rates. Three carpet fresheners decreased Der p 1 assay rate responses in
      a concentration-dependent manner. Two carpet fresheners noticeably increased Der
      f 1 assay reaction rates in both the screening and the concentration-response
      tests. Powdered pesticides increased reaction rates in the Bla g 1 assays and
      increased the slope of the dilution curve compared with that of the purified
      allergen. Salt decreased the reaction rates of Bla g 1 assays at allergen
      concentrations greater than 0.01 U/mL. For each of the four allergens, the
      largest effects of dust additives occurred when secondary antibody binding was
      altered. CONCLUSIONS: Some common household dust components can introduce
      systematic error into immunoassays for arthropod allergens.

PMID- 10202362
TI  - Identification of a highly promiscuous and an HLA allele-specific T-cell epitope
      in the birch major allergen Bet v 1: HLA restriction, epitope mapping and TCR
      sequence comparisons.
AB  - BACKGROUND: Allergen-specific CD4+ T cells play an important regulatory role in
      atopic allergy. OBJECTIVE: To investigate the human leucocyte antigen (HLA)
      restriction and T-cell receptor (TCR) usage of allergen-specific T-cell clones
      (TCCs) that react with defined epitopes of Bet v 1, the major birch pollen
      allergen. METHODS: Five Bet v 1-specific TCCs derived from two birch pollen
      allergic individuals and specific for Bet v 1, were epitope-mapped with
      overlapping synthetic peptides. In addition, HLA-restriction and TCR CDR3
      sequences were determined. RESULTS: Three TCCs reacted with a Bet v 1 peptide
      containing amino acid residues 21-33 (BP21), the other two TCCs reacted with a
      minimal peptide comprising residues 37-45 (BP37). Studies using neutralizing anti
      HLA-monoclonal antibodies and HLA-typed APCs showed that the BP37-specific TCCs
      were restricted by a HLA-DQA1*0301/DQB1*0603 heterodimer. In contrast, BP21 was
      recognized in a highly promiscuous manner. TCCs recognizing this sequence were
      restricted by HLA-DPB1*0201, a HLA-DQA1*0201/DQB1*0201 heterodimer, or HLA
      DRB3*0101. Reverse transcription-polymerase chain reaction with primers for all
      known TCRAV and TCRBV gene segments, followed by CDR3 region sequencing, revealed
      the usage of five different TCRAV and four different TCRBV gene segments by the
      TCCs, as well as diversity in the joining region. All BP21-specific TCCs
      contained a negatively charged residue in their CDR3alpha regions, the CDR3beta
      regions showed a high concentration of polar and OH-group bearing residues. BP37
      specific TCCs shared the amino acid combination LY in the middle of their
      CDR3alpha regions, the CDR3beta regions showed high concentration of OH-group
      bearing or charged residues. CONCLUSIONS: This study shows the existence of a
      highly promiscuous T-cell epitope in Bet v 1. The presence of additional T-cell
      epitopes in Bet v 1 may, however, hamper the clinical applicability of the
      epitope. Likewise, the diversity in TCR usage by T cells recognizing the epitope
      does not support the development of TCR-directed immunotherapy for birch pollen
      allergy.

PMID- 10202363
TI  - Sequence polymorphism of the group 1 allergen of Bermuda grass pollen.
AB  - BACKGROUND: Cyn d 1, the major allergen of Bermuda grass pollen, consists of a
      number of isoforms. OBJECTIVE: To examine the extent of sequence variation of Cyn
      d 1 isoforms at the molecular level. METHODS: A Bermuda grass pollen lambdaZAP II
      cDNA expression library was immunoscreened with anti-Cyn d 1 monoclonal
      antibodies. The reactive clones were isolated, subcloned into Escherichia coli,
      and sequenced. Some of them were expressed in the yeast Pichia pastoris to obtain
      recombinant Cyn d 1 proteins. RESULTS: Ten cDNA clones were obtained, all these
      clones encode the full length of Cyn d 1 protein. Their deduced mature proteins
      can be grouped into: the long ones with 246 amino acids, and the short ones with
      244 amino acids. The last two amino acids (AG) of the long Cyn d 1 are deleted in
      the short Cyn d 1. The remaining amino acid sequences share more than 98%
      identity; a total of nine amino acid variations were observed. Two recombinant
      Cyn d 1 proteins (rCyn d 3-2 and rCyn d 5-4) with three amino acid substitutions
      showed differential IgE-binding profiles. CONCLUSION: The present study extended
      our understanding of the primary structure of isoforms of Cyn d 1.

PMID- 10202364
TI  - Monitoring allergen immunotherapy of pollen-allergic patients: the ratio of
      allergen-specific IgG4 to IgG1 correlates with clinical outcome.
AB  - BACKGROUND: Although allergen immunotherapy has been established as a treatment
      of type I allergy back in 1911, until now the underlying mechanisms have not been
      fully understood, nor are there any parameters which would allow one to monitor
      an ongoing treatment or to assess therapeutic success in the meantime. OBJECTIVE:
      We wanted to define allergen-specific parameters that change due to treatment in
      correlation with the clinical outcome. METHODS: We conducted a controlled study
      with grass pollen-allergic children and compared allergen-specific antibody
      titres before and 1 year after the onset of immunotherapy in contrast with
      untreated allergic and healthy children. Two recombinant forms of the major
      allergen group V of Phleum pratense (Phl p 5) served as model allergens. RESULTS:
      No change in IgE levels and no significant reduction of skin prick test (SPT)
      reactivity were seen. On the other hand, a significant reduction of symptom
      scores in the treated group and a significant rise in allergen-specific IgG1,
      IgG2 and IgG4 due to the treatment could be observed, but in neither case could
      we establish a correlation between the increasing amounts of the single antibody
      classes and the reduction of symptom scores. But most interestingly, when
      comparing the ratio of IgG4 to IgG1 with the symptom scores, we found significant
      correlations. Nevertheless, treated allergic patients still differ considerably
      from healthy controls as nonatopics have hardly any measurable allergen-specific
      IgG antibodies and no IgE antibodies at all. CONCLUSION: The ratio of IgG4 to
      IgG1 can serve as a valuable parameter that allows us to assess the success of
      immunotherapy already 1 year after the onset. The increase of specific IgG1 in
      relation to IgG4 during treatment reflects a possible influence of this subclass
      on the induction of tolerance towards allergens.

PMID- 10202365
TI  - Cow's milk protein-specific IgE concentrations in two age groups of milk-allergic
      children and in children achieving clinical tolerance.
AB  - BACKGROUND: IgE-mediated cow's milk protein allergy (CMPA) is usually outgrown in
      children by the age of 3 years. The immunological responses to cow's milk
      proteins in children who achieve tolerance, in comparison with those who remain
      allergic, however, are not well described. OBJECTIVE: To compare the level of
      cow's milk protein-specific IgE among children with documented CMPA under the age
      of 3 years, another group over the age of 9 years (persistent allergy), and in
      another group of children in whom clinical tolerance developed. METHODS: Stored
      sera from children with CMPA were analysed for IgE antibodies specific for whole
      cow's milk, casein, whey, alpha-lactalbumin (ALA), beta-lactoglobulin (BLG), and
      bovine serum albumin (BSA) using the Pharmacia CAP System FEIA. RESULTS: Within
      each group of CMPA children, the concentration of specific IgE antibody to casein
      proteins was not significantly different from that to whey proteins. However,
      children in the group with CMPA over 9 years of age had significantly greater
      concentrations of whole milk (P = 0.02) and casein-specific (P = 0. 04) IgE
      antibodies compared with the group of children with CMPA under age 3 years.
      Children under the age of 3 years had a higher median concentration of casein
      specific IgE (20.2 vs. 5.5, P = 0.04) than another group of 11 children (mean age
      3.5 years), who later lost their milk allergy. Out of 16 children who lost
      sensitivity to milk, 75% had milk-specific IgE levels below 14.3 kUA/L (median,
      1.3 kUA/L). CONCLUSIONS: Although a dominant allergenic milk protein fraction was
      not identified within either of the two age groups, those with persistent CMPA
      over age 9 years had significantly elevated levels of milk and casein-specific
      IgE compared with younger children with CMPA.

PMID- 10202366
TI  - Atopy patch test reactions are associated with T lymphocyte-mediated allergen
      specific immune responses in atopic dermatitis.
AB  - BACKGROUND: Positive test reactions to epicutaneous application of aeroallergens
      served as a model of 'early' eczema in atopic dermatitis (AD) in a number of
      dermato-immunological studies. However, no quantitative evaluation has been
      performed so far comparing specific T-cell activation parameters in the
      peripheral blood of AD patients with positive or negative atopy patch tests
      (APT). OBJECTIVE: The purpose of this study was to investigate specific
      immunological parameters in patients with atopic dermatitis showing positive or
      negative atopy patch tests reactions. METHODS: APT results (n = 96) were compared
      with allergen-specific IgE, specific lymphocyte proliferation, and the expression
      of 'activation' markers on peripheral blood T-cells upon in vitro stimulation
      with house dust mite, cat or grass pollen allergens. RESULTS: Only a
      subpopulation (48%) of patients sensitized to aeroallergens (i.e. specific IgE >
      0.7 kU/L) developed APT-reactions to the corresponding allergen. APT reactions
      were, however, significantly associated with allergen specific lymphocyte
      proliferation (p < 0.0001), and a higher number of CD54+ or CD30+ T-cells (p <
      0.05) upon in vitro stimulation. CONCLUSION: The association of delayed skin
      reactions with allergen specific T-cell parameters in the blood points to an
      immunologically mediated mechanism leading to positive reactions in the APT.

PMID- 10202367
TI  - Asthma, atopy and Chlamydia pneumoniae antibodies in adults.
AB  - BACKGROUND: Factors involved in the development of inflammation and asthma in
      nonatopic subjects have remained largely obscure, although there is some evidence
      to suggest that certain infections may play a role. OBJECTIVE: We investigated
      the association between serological evidence of Chlamydia pneumoniae infection
      and asthma in adults, and the possible modifying effect of the patients' atopic
      status on this association. METHODS: Four hundred and thirty consecutive patients
      who attended the hospital between 1992 and 1993 with symptoms suggestive of
      asthma, rhinitis or allergy were enrolled. Diagnostic procedures including lung
      function measurements and skin-prick tests were performed in all patients. The
      patients with established asthma (n = 332) were divided into those with recent
      asthma (n = 224, onset 1985 onward) and longstanding asthma (n = 108, onset
      before 1985). The controls (n = 98) comprised all subjects who did not meet the
      criteria of asthma. Serum immunoglobulin (Ig)G, IgA and IgM antibodies to C.
      pneumoniae were measured by the microimmunofluorescence test. RESULTS: In women,
      the prevalences of elevated IgG (a titre of >/= 128) and IgA (>/= 32) antibody
      levels and the age-adjusted geometric mean titres (GMT) of IgG and IgA antibodies
      were invariably highest among subjects with nonatopic longstanding asthma.
      Elevated IgG titres in women occurred in 11% of controls, in 28% of nonatopic
      recent onset asthmatics, and in 43% of asthmatics with nonatopic longstanding
      disease; for men the respective figures were 33, 50 and 64%. Logistic regression
      analysis controlling for age, sex and smoking showed that asthma was
      significantly associated with elevated IgG antibody levels to C. pneumoniae (odds
      ratio 3.3, 1.6-6.8 for longstanding asthma, 2.3, 1. 2-4.4 for recent asthma, and
      among women only 4.2, 1.6-10.9 for longstanding asthma, and 3.0, 1.3-7.2 for
      recent asthma). When the atopics and nonatopics were analysed separately, an even
      stronger relationship in the nonatopics was obtained for longstanding asthma
      (6.0,2.1-17.1). In contrast, the relationship between atopic asthma, either
      recent or longstanding, and elevated IgG titres was not significant, indicating
      that asthma per se does not predispose to C. pneumoniae infection. CONCLUSIONS:
      Asthma was significantly associated with elevated IgG antibody levels to C.
      pneumoniae, and this association was strongest for nonatopic longstanding asthma.

PMID- 10202368
TI  - Nedocromil sodium eye drops are more effective than sodium cromoglycate eye drops
      for the long-term management of vernal keratoconjunctivitis.
AB  - BACKGROUND: Vernal keratoconjunctivitis (VKC) is a severe though transient form
      of ocular allergy, predominant in young males, which requires careful management.
      Corticosteroids are effective but also cause serious topical side-effects in the
      eye, such as glaucoma and cataracts. The safer, mast cell stabilizing anti
      inflammatories (commonly sodium cromoglycate) therefore have an important role.
      This parallel group study compared efficacy, tolerability and safety of sodium
      cromoglycate 2% with nedocromil sodium 2%, administered as one drop per eye four
      times daily for a period of 5 months. METHODS: Children aged 4-17 years, with a
      diagnosis of mostly limbal VKC in the last 12 months, entered a 2-week baseline
      during which they used only artificial tears, and were then randomized to
      treatment, in groups of 18, on an investigator single-masked basis. Daily symptom
      diary cards were kept by patients/guardians, and VKC was assessed by the
      clinician at approximately monthly intervals. Dexamethasone was provided for
      rescue control of severe symptoms, if needed. RESULTS: A total of 34 patients
      completed the study. Both trial treatments produced rapid improvements and many
      ocular signs and symptoms, including Trantas' dots, chemosis, itching, soreness
      and sticky discharge, were fully controlled by the end of the study. However,
      nedocromil sodium took effect more quickly, with a significant reduction compared
      to sodium cromoglycate for itching, grittiness, hyperaemia and keratitis within 6
      weeks. In addition, nedocromil sodium was the more efficacious overall
      (significant vs sodium cromoglycate for hyperaemia, keratitis, papillae and
      pannus at 22 weeks). Both treatments were well tolerated and without serious
      adverse effects. Final opinions favoured nedocromil sodium, with full control of
      VKC recorded for 94% (patient opinion) and 100% (clinician opinion) of this
      treatment group, compared with 29% and 0%, respectively, in the sodium
      cromoglycate group. CONCLUSIONS: Nedocromil sodium 2% eye drops is significantly
      more effective than sodium cromoglycate for treatment of VKC.

PMID- 10202369
TI  - Tumour necrosis factor alpha (TNFalpha) in tears of atopic patients after
      conjunctival allergen challenge.
AB  - BACKGROUND: Proinflammatory cytokines, such as TNFalpha are involved in the
      pathogenesis of allergic rhinitis and asthma. OBJECTIVE: Our aim was to study the
      tear fluid TNFalpha levels in atopic patients before and after topical ocular
      allergen challenge. METHODS: Thirteen patients were first challenged with topical
      allergen in the left eye and then dilution buffer in the right eye. Tear fluid
      samples were collected before the challenges and after 5, 30 and 60 min. Clinical
      symptoms were scored. Tear fluid TNFalpha concentrations were measured using a
      double-antibody radioimmunoassay. TNFalpha release rates were calculated using
      the tear fluid flow in the collection capillary as an estimate for the tear
      secretion rate. RESULTS: The mean baseline TNFalpha concentrations (ng/L) were
      1310 (allergen-challenged eye) and 967 (control eye), and release rates (pg/min)
      1.81 (allergen-challenged eye) and 1.39 (control eye), respectively. In the
      allergen-challenged eye, TNFalpha concentrations and release rates were 1479 and
      4.30 (5 min), 1367 and 3.20 (30 min) and 1426 and 3.80 (60 min). In the control
      eye, TNFalpha concentrations and release rates were 746 and 0.67 (5 min), 1001
      and 0.92 (30 min) and 1504 and 1.05 (60 min). The release rates of the allergen
      challenged eye were significantly increased at all time points after the
      challenge when compared with the baseline or the control eye. CONCLUSION:
      Increased TNFalpha release rates suggest that this cytokine is an early mediator
      of allergy after conjunctival challenge.

PMID- 10202370
TI  - Enhanced basophil histamine release and neutrophil chemotactic activity
      predispose grain dust-induced airway obstruction.
AB  - BACKGROUND: The pathogenic mechanism of grain dust (GD)-induced occupational
      asthma (OA) remains unclear. OBJECTIVE: To understand further the mechanism of GD
      induced OA. METHODS: Fifteen employees working in a same GD industry, complaining
      of work-related respiratory symptoms, were enrolled and were divided into two
      groups according to the GD-bronchoprovocation test (BPT) result: six positive
      responders were grouped as group III, nine negative responders as group II and
      five healthy controls as group I. Serum GD-specific immunoglobulin (Ig)E (sIgE),
      specific IgG (sIgG) and specific IgG4 (sIgG4) antibodies were detected by enzyme
      linked immunosorbent assay. Basophil histamine release was measured by the
      autofluorometric method, and changes of serum neutrophil chemotactic activity
      were observed by the Boyden chamber method. RESULTS: For clinical parameters such
      as degree of airway hyperresponsiveness to methacholine, duration of respiratory
      symptoms, exposure duration, and prevalences of serum sIgE, sIgG and sIgG4
      antibodies, there were no significant differences between group II and III (P >
      0.05, respectively). Serum neutrophil chemotactic activity increased
      significantly at 30 min and decreased at 240 min after the GD-BPT in group III
      subjects (P < 0.05, respectively), while no significant changes were noted in
      group II subjects (P > 0.05). Basophil histamine release induced by GD was
      significantly higher in group III than those of group I or group II (P < 0.05,
      respectively), while minimal release of anti-IgG4 antibodies was noted in all
      three groups. CONCLUSIONS: These results suggest that enhanced basophil histamine
      release and serum neutrophil chemotactic activity might contribute to the
      development of GD-induced occupational asthma.

PMID- 10202371
TI  - Endothelial cells upregulate eosinophil superoxide generation via VCAM-1
      expression.
AB  - BACKGROUND: In vitro eosinophil (EOS) adhesion to recombinant human (rh)-vascular
      cell adhesion molecule (VCAM)-1 stimulates superoxide anion (O2-) generation and
      enhances formyl-methionyl-leucyl phenylalanine (FMLP)-activated O2- generation.
      Therefore, EOS adhesion via VLA-4 to VCAM-1 expressed on endothelium may be
      instrumental in the selective recruitment and function of EOS in airway
      inflammation. OBJECTIVE: We hypothesized that EOS interaction with endothelial
      cells expressing VCAM-1 will undergo an enhancement in inflammatory function.
      METHODS: To determine this possibility, human umbilical vein endothelial cells
      (HUVEC) were stimulated with either a combination of interleukin (IL)-4 and
      tumour necrosis factor (TNF)-alpha (100 pM) or medium alone for 24 h; the
      expression of adhesion proteins on HUVEC and their effect on EOS O2- generation
      was subsequently determined. RESULTS: As determined by both enzyme-linked
      immunosorbent assay and flow cytometry, IL-4 and TNFalpha acted synergistically
      to induce VCAM-1 expression on HUVEC. Treating HUVEC with IL-4/TNFalpha also
      increased EOS adhesion and primed subsequent FMLP (0.1 microM) activated EOS O2-
      generation. Although EOS adhesion was partially inhibited by both antialpha4 and
      antibeta2 monoclonal antibodies (MoAbs), O2- generation was completely inhibited
      by either antialpha4 integrin MoAb (HP1/2) or anti-VCAM MoAb (BBIG-V1).
      Furthermore, enhanced O2- generation, but not adhesion, associated with IL-4 +
      TNFalpha-treatment of HUVEC was inhibited when EOS were treated with the platelet
      activating factor (PAF)-antagonist WEB 2086 (20 microM), thus suggesting an
      involvement of PAF in priming EOS. However, paraformaldehyde fixation of IL-4/TFN
      alpha treated HUVEC did not significantly alter EOS function. CONCLUSIONS: These
      results suggest EOS adhesion to endothelial cells via an VLA-4/VCAM-1 interaction
      may be important in the development of the function of this cell. Furthermore,
      our results suggest that modulation of EOS function involves two priming factors:
      EOS adhesion to HUVEC expressing VCAM-1 and PAF.

PMID- 10202372
TI  - The route of antigen delivery determines the airway and lung tissue mechanical
      responses in allergic rats.
AB  - BACKGROUND: Previous results have shown tissue constriction in allergic animals
      following inhalation of an antigen. Further studies have demonstrated a differing
      response pattern in airway and parenchymal mechanics following inhaled (i.h.) or
      intravenous (i.v.) delivery of methacholine (MCh). OBJECTIVE: The purpose of this
      study was to compare the acute allergic response in airway and parenchymal
      mechanics following i.h. and i.v. antigen challenge. METHODS: Brown Norway rats
      were sensitized to ovalbumin (OVA). Rats were anaesthetized, paralysed, and
      thoracotomized, and lung input impedance (ZL) between 0.5 and 21 Hz was measured
      using small-amplitude pseudo-random oscillations at control, after saline, and
      for up to 1 h after either i.h. (n = 7) or i.v. (n = 5) administration of OVA. ZL
      was evaluated in terms of airway resistance (Raw) and inertance (Iaw), and a
      constant phase tissue parenchymal damping (G) and elastance (H). RESULTS:
      Following i.h. OVA challenge elevations were found in Raw [192 +/- 32 (SE) %], G
      (223 +/- 21%), and H (141 +/- 5%). Raw showed higher elevation after i.v.
      challenge (418 +/- 57%), whereas the elevation in G (278 +/- 30%) and H (130 +/-
      4%) was approximately equal to those seen following inhalation of an antigen.
      CONCLUSIONS: Delivery (i.v.) of an antigen produces a significantly higher
      response in airway resistance, whereas inhaled antigen results in a mixed airway
      and parenchymal response.

PMID- 10202373
TI  - Commentary: Free radicals in gliomas: friend or foes?

PMID- 10202374
TI  - Salt sensitivity correlates positively with insulin sensitivity in healthy
      volunteers.
AB  - BACKGROUND: The aim of the study was to assess the relationship between insulin
      sensitivity and salt sensitivity in healthy subjects who display a wide range of
      insulin sensitivity. As a secondary objective, we assessed the relationship
      between salt sensitivity and the other characteristics of the insulin resistance
      syndrome. STUDY DESIGN: Forty-seven normotensive volunteers (age 34 +/- 15 years)
      with a normal glucose tolerance test were selected. We measured insulin
      sensitivity using the hyperinsulinaemic euglycaemic clamp (50 mU kg-1 h-1), blood
      pressure, waist-to-hip ratio, fasting insulin levels, serum lipids and uric acid
      levels. In a subset of 21, representing a wide range of insulin sensitivity, salt
      sensitivity was determined as the difference in mean arterial blood pressure
      (MAP) at the end of a high-salt diet (10 g of NaCl per day for 1 week) vs. a low
      salt diet (2 g of NaCl per day for 1 week). RESULTS: Insulin sensitivity (M/I
      value, range 0.49-4.41 mg kg-1 min-1 per pmol L-1 x 100) was negatively
      correlated with MAP (r = -0.54, P < 0. 001) and waist-to-hip ratio (r = - 0.59, P
      < 0.001) but positively correlated with salt sensitivity (r = 0.47, P = 0.03).
      Salt sensitivity also correlated with high-density lipoprotein (HDL)-cholesterol
      (r = 0.46, P = 0.038) but not with waist-to-hip ratio, fasting insulin levels,
      low-density lipoprotein cholesterol, serum triglycerides or serum uric acid.
      CONCLUSIONS: In healthy normotensive subjects who display a wide range of insulin
      sensitivity, as measured with the euglycaemic clamp technique, salt sensitivity
      correlates positively with insulin sensitivity and HDL-cholesterol, but not with
      the other characteristics of the insulin resistance syndrome.

PMID- 10202375
TI  - In vivo kinetics of human apolipoprotein A-I variants in rabbits.
AB  - BACKGROUND: Genetic variants of human apolipoprotein (apo) A-I, the major protein
      component of high-density lipoprotein (HDL), with a single amino acid
      substitution have been reported, and some of these result in very low plasma HDL
      cholesterol (C) levels. Examining the kinetics of radiolabelled apolipoprotein is
      a straightforward technique for determining its metabolism in vivo. In this
      study, we investigated the in vivo kinetics of several human apo A-I variants,
      which we had identified previously, in rabbits. MATERIALS AND METHODS: Apo A-I
      variants from heterozygous carriers of Lys-107-->0, Lys-107-->Met, Pro-3-->Arg,
      Pro-4-->Arg, Pro-165-->Arg and Glu-198-->Lys and the corresponding normal apo A-I
      were purified and then radioiodinated with 131I and 125I. A kinetic study of apo
      A-I variants was performed in normolipidaemic rabbits after simultaneous
      injection of the two isotopes that had been incorporated into HDL. The fractional
      catabolic rate (FCR) was calculated from the radioactive decay curve. RESULTS:
      Acidic mature (negatively charged) apo A-I variants caused by a single amino acid
      substitution (Lys-107-->0, and Lys-107-->Met) were catabolized faster (FCR, 1.931
      +/- 0.539 per day vs. 1.636 +/- 0.460 per day, P </= 0.01 using the Wilcoxon
      signed-rank test) and basic mature (positively charged) apo A-I variants (Pro-3-
      >Arg, Pro-4-->Arg, Pro-165-->Arg and Glu-198-->Lys) were catabolized more slowly
      (FCR 1.470 +/- 0.380 per day vs. 1.654 +/- 0.430 per day, P </= 0.01) than the
      corresponding normal mature apo A-I in vivo in rabbits. In addition, an inverse
      linear relationship was observed between the deviation in the FCR of variant
      human apo A-I from that of normal human apo A-I and the number of electric
      charges that the apo A-I variant carried (r = -0. 90, k = -0.188, P = 0.0003), as
      assessed by a linear regression analysis, suggesting that the electric charge of
      apo A-I variants may determine, at least in part, its in vivo kinetics in
      rabbits. CONCLUSIONS: Genetic variants of apo A-I with a single amino acid
      substitution show abnormal kinetics, and the electric charge of a apo A-I variant
      could contribute to determining its kinetics in vivo in this xenologous model.

PMID- 10202376
TI  - Post-prandial chylomicron response may be predicted by a single measurement of
      plasma apolipoprotein B48 in the fasting state.
AB  - BACKGROUND: The clearance of chylomicron remnants was assessed in normolipaemic,
      dyslipidaemic and obese male subjects by monitoring the plasma kinetics of
      apolipoprotein (apo) B48, retinyl palmitate and triglyceride after a lipid meal.
      Regression analysis of fasting plasma apo B48 with the area under the post
      prandial curves of apo B48, retinyl ester and triglyceride was carried out in
      order to determine whether the post-prandial response could be predicted by the
      fasting concentration of this exclusive chylomicron marker. MATERIALS AND
      METHODS: Fasted subjects were given an oral fat load supplemented with retinyl
      palmitate, and blood samples were drawn over a 10-h period. Apolipoprotein B48
      was determined by Western blotting in the plasma density fraction less than 1.063
      g mL-1. Plasma retinyl palmitate and triglyceride were determined by high
      performance liquid chromatography (HPLC) and colorimetric procedures
      respectively. The areas under the apo B48, retinyl ester and triglyceride curves
      were determined by integration. Relationships between the post-prandial response
      and the fasting concentration of apolipoprotein B48 were assessed using least
      squares regression analysis. RESULTS: We found a strong positive relationship
      between the fasting plasma concentration of apo B48 and the post-prandial
      kinetics of apo B48. Similarly, there was a positive relationship of fasting apo
      B48 with the retinyl ester area under the curve. Collectively, the data suggested
      that chylomicron remnant kinetics can be predicted based on the fasting level of
      apo B48. There was also a significant but weaker relationship of fasting apo B48
      with post-prandial triglyceride kinetics, consistent with removal of this lipid
      by hydrolytic mechanisms in addition to particle uptake. CONCLUSION: The fasting
      plasma concentration of apo B48 appeared to be a good surrogate marker for the
      degree of post-prandial lipidaemia and may circumvent the need for oral fat
      challenges. Moreover, in the fasting state apo B48 concentration is a marker of
      chylomicron remnants, which are considered to be the proatherogenic form of these
      intestinally derived lipoproteins.

PMID- 10202377
TI  - Review: Ageing and hormones.
AB  - With ageing, there is a decline in hormone levels, including oestrogen,
      testosterone, dehydroepiandrosterone and growth hormone. Replacement of these
      hormones has been investigated and reviewed in this paper. There are still
      controversies regarding the benefits and risks of replacement therapy.

PMID- 10202378
TI  - Expression of genes involved in calcium absorption in human duodenum.
AB  - BACKGROUND: The role of vitamin D metabolites in the regulation of expression of
      genes involved in dietary calcium absorption by the human intestine remains
      poorly understood despite much work in animals. MATERIALS AND METHODS: To
      investigate this, we measured the expression of transcripts for two of these
      genes, calbindin-D9k and the basolateral membrane calcium pumping ATPase, PMCA1,
      in duodenal endoscopic biopsies from 40 subjects. Northern blots were hybridized
      with previously characterized probes, and the signal was quantified by phosphor
      imaging. These transcript levels were related to circulating vitamin D
      metabolites and also analysed according to the vitamin D receptor gene TaqI
      polymorphism determined in DNA from blood. RESULTS: Plasma 1,25
      dihydroxycholecalciferol correlated significantly with calbindin-D9k RNA (r =
      0.4, P < 0.02) but not with PMCA1. Plasma 25-OH-cholecalciferol was not
      correlated with transcripts for either gene and, furthermore, the mean levels of
      these transcripts did not differ significantly when grouped by vitamin D receptor
      genotype. CONCLUSION: In normal humans, 1, 25-dihydroxycholecalciferol has a
      small but significant relationship to duodenal expression of calbindin-D9k, but
      not to PMCA1 expression.

PMID- 10202379
TI  - Dynamics of reactive oxygen intermediate production in human glioma: n-6
      essential fatty acid effects.
AB  - BACKGROUND: Reactive oxygen intermediates (ROIs) are important signals
      controlling cell growth and cell death. Local essential fatty acid (EFA)
      deficiencies in tumour cells may limit tumour ROI generation. This deficiency may
      be rectified by the addition of exogenous EFA. MATERIALS AND METHODS: The n-6 EFA
      effects on tumour ROIs were analysed in terms of kinetics, dose-response and
      individual cell type responses using flow cytometry of intracellular 2',7'
      dichlorofluorescin oxidation. ROI formation in 30 gliomas and five paired samples
      of normal brain tissue, > 500 000 cells per specimen, was analysed every 10 s for
      0-25 min. RESULTS: Tumour cell basal ROI was lower than normal brain tissue ROI
      from the same subjects (P < 0.00002). Normal and tumour cell ROIs were stimulated
      by 4-40 micromol L-1 n-6 EFAs, arachidonic acid (AA) and gamma-linolenic acid
      (GLA). The stimulated ROI rate was exponential, with the maximum dependent on EFA
      concentration and tumour grade. CONCLUSIONS: EFAs stimulated tumour cells more
      than normal cells (P < 0.0000017, n = 71) and increased ROIs in glial fibrillary
      acidic protein-positive cells in tumours. This indicated high sensitivity of
      glioma cell ROIs to n-6 EFAs.

PMID- 10202381
TI  - Review: The role of glutathione in the regulation of apoptosis.
AB  - Recent advances in the study of the regulation of cell death by apoptosis suggest
      that changes in mitochondrial permeability frequently precede the development of
      morphological features such as chromatin condensation, phosphatidylserine
      inversion of the outer cell membrane and the activation of endonucleases. There
      is evidence that this permeability transition is associated with, and may be
      regulated by, changes in the intracellular redox potential. The role of the
      tripeptide thiol glutathione in the regulation of apoptosis-associated redox
      changes and the control of mitochondrial membrane permeability is reviewed in
      this article.

PMID- 10202380
TI  - Determination of heparin-induced IgG antibody in heparin-induced thrombocytopenia
      type II.
AB  - BACKGROUND: Heparin-induced thrombocytopenia is a relatively uncommon but severe
      side-effect of heparin therapy. Heparin-induced IgG antibody has been elucidated
      to be the main isotype and the most pathogenic antibody in the pathophysiology.
      As affected patients are at high risk of developing thrombotic events,
      confirmation of the clinical diagnosis and avoidance of heparin re-exposure are
      important and desirable. MATERIALS AND METHODS: In the present study, heparin
      induced IgG was measured by the binding of neoantigens, which were prepared by
      incubating FITC-heparin with platelet factor 4 present in normal serum. The cross
      reactivities of heparin-induced IgG with low-molecular-weight heparin and
      danaparoid were analysed by competitive binding. RESULTS: A total of 81
      clinically suspected heparin-induced thrombocytopenia type II patients were
      analysed. Thirty-seven of 38 heparin-induced thrombocytopenia type II patients,
      in whom thromboembolism was confirmed by objective methods, had elevated relative
      fluorescence intensity ratios (patient normal control) and 36 had positive
      heparin-induced platelet activation results. The prevalence of heparin-induced
      IgG in heparin-induced thrombocytopenia type II patients was 97.4%. Positive
      heparin-induced IgG results were: 0/319 healthy volunteers, 0/38 other thrombo
      cytopenia and 2/56 heparin/low-molecular-weight heparin-receiving patients
      without thrombocytopenia, 2/41 hyperbilirubinaemic patients and 2/50
      hyperlipidaemic patients. A small amount of cross-reaction assays showed similar
      results as obtained in heparin-induced platelet activation. CONCLUSION: Our
      results suggest that a very high frequency of heparin-induced IgG in heparin
      induced thrombocytopenia type II patients can be detected using a novel antigen
      assay. The rapid determination of pathogenic heparin-induced IgG may be a useful
      tool for the rapid diagnosis of heparin-induced thrombocytopenia type II that
      could facilitate further management of the patients.

PMID- 10202382
TI  - Proteolytic destruction of functional proteins by phagocytes in human
      peritonitis.
AB  - BACKGROUND: Besides phagocyte-derived oxidative autoaggression, proteolytic
      destruction of functional proteins in the peritoneal cavity may also be involved
      in the pathomechanism of secondary peritonitis. To evaluate the pattern of
      proteolysis, 43 patients undergoing initial operation for acute peritonitis (n =
      30) or scheduled abdominal lavages (Etappenlavage) for resolution of persistent
      peritonitis (n = 13) and 16 surgical patients with abdominal exudation without
      peritonitis were enrolled in our study. MATERIALS AND METHODS: Thirty blood
      samples and purulent exudates were taken simultaneously in each peritonitis group
      at the surgical interventions. Sixteen clear exudates were obtained from patients
      with post-operative non-infectious irritations. The following parameters were
      measured: (a) elastase (from neutrophils) and cathepsin B (from
      monocytes/macrophages); (b) alpha1-proteinase inhibitor (alpha1PI) and overall
      cysteine proteinase inhibitor capacity; and (c) opsonic activity and degradation
      products of fibrinogen, complement C3 and immunoglobulin IgG. RESULTS:
      Circulating levels of phagocyte proteinases and of alpha1PI were significantly
      elevated, whereas antigen concentrations and opsonic activity of C3 and IgG were
      slightly reduced in peritonitis patients compared to healthy volunteers. No
      degradation products were detectable in patients' blood. Discharge of phagocyte
      proteinases was even more pronounced in both types of peritonitis exudates.
      Although most of the elastase was complexed with alpha1PI, active elastase and
      its specific fibrinogen split product was found along with significantly reduced
      inhibitory capacity for elastase and cysteine proteinases. Local opsonic activity
      was dramatically diminished because of proteolytic degradation of C3 and IgG.
      Despite some phagocyte proteinase release, no destruction of functional proteins
      was seen in clear exudates. CONCLUSIONS: Higher values of extracellularly
      released phagocyte proteinases concomitant with lower opsonin activity in
      exudates from patients with persistent peritonitis can be taken as a further hint
      of the involvement of local proteolysis-induced pathomechanisms in the
      development of lethal multiple organ failure, which occurred more frequently in
      patients with persistent peritonitis (54%) than in those with acute peritonitis
      (27%).

PMID- 10202383
TI  - Effects of tumour necrosis factor alpha and melphalan on the cytokine production
      of circulating T cells in patients with cancer.
AB  - BACKGROUND: The objective of the present study was to investigate the effects of
      isolated limb perfusion (ILP) with tumour necrosis factor alpha (TNF-alpha) and
      melphalan on circulating T cells from cancer patients using two different
      methods. DESIGN: Eight patients undergoing an ILP entered the study. At first,
      the number of T cells at several time points was determined using FACScan.
      Subsequently, production of interferon gamma (IFN-gamma) (T-helper 1) and
      interleukin (IL) 4 (T-helper 2) was measured at the intracytoplasmic level after
      stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin. IFN-gamma,
      IL-4 and IL-2 (also T-helper 1) production in the whole-blood cell culture system
      was then determined after stimulation with a combination of anti-CD3/anti-CD28
      monoclonal antibodies. RESULTS: An enormous decrease in the number of circulating
      T cells was observed. In the remaining T-cell population cytokine production (IL
      2, IL-4, IFN-gamma) was depressed, showing the same pattern in both methods. No
      difference could be detected between the effect of TNF-alpha and melphalan on Th1
      cells and Th2 cells. CONCLUSIONS: The results demonstrate that TNF-alpha and
      melphalan reduce the number of circulating T cells and at the single-cell level
      decrease cytokine production in the remaining circulating T cells. No selective
      effect of TNF-alpha on Th1 or Th2 cells could be detected. If the impaired T-cell
      function is representative of all T cells remaining in the systemic circulation,
      this could help to explain the tolerability of high TNF concentrations after ILP,
      perhaps by decreasing the synthesis and production of T-cell-derived cytokines.

PMID- 10202384
TI  - Hyperosmolar saline induces airway resistance changes and neuropeptide release: a
      comparison with the effect of capsaicin, potassium and histamine.
AB  - BACKGROUND: Healthy subjects do not show any bronchoconstricting response to
      inhalation of hypertonic saline, in contrast to subjects with symptoms of asthma.
      There is evidence indicating that these airway reactions may be related to
      stimulation of sensory nerves. MATERIALS AND METHODS: We investigated the effects
      of hyperosmolar solutions on the changes in airway resistance as well as on
      release of neuropeptides from an isolated and perfused guinea pig lung model.
      RESULTS: We observed that hyperosmolar saline (HS), capsaicin, potassium and
      histamine induced different patterns of response in airway resistance and
      neuropeptide release. HS 3.6% induced a biphasic response in airway resistance.
      Initially a minor relaxation, 4 +/- 1 cmH2O mL-1 min (P < 0.05), followed by a
      contraction, 22 +/- 3 cmH2O mL-1 min (P < 0.01). This was associated with release
      of calcitonin gene-related peptide (CGRP) 7.7 +/- 1.9 fmol mL-1 g (P < 0.01), but
      not of neurokinin A (NKA), a known bronchoconstrictor. Mannitol, at the same
      osmolarity as HS 3.6%, did not elicit a change in airway resistance, CRGP or NKA
      release. Capsaicin at 10-6 mol L-1 and potassium at 70 mmol L-1 induced a
      profound increase in airway tone (50 +/- 9 and 42 +/- 8 cmH2O mL-1 min
      respectively; P < 0.01) and elevation of both CGRP (6.4 +/- 1.9 and 3.9 +/- 1.1
      fmol mL-1 g respectively; P < 0.05) and NKA (3.3 +/- 1.0 and 1.0 +/- 0.2 fmol mL
      1 respectively; P < 0.05). Histamine increased the airway resistance by 42 +/- 8
      cmH2O mL-1 min (P < 0.01) but had no effect on either CGRP or NKA release.
      CONCLUSIONS: In healthy guinea pigs, hyperosmolar saline 3.6% initially caused
      relaxation of the airways followed by contraction and induced release of CGRP-LI.
      This was not seen with mannitol at the same osmolarity as for the hyperosmolar
      saline.

PMID- 10202386
TI  - Comments on the importance of diet and nutrition in cancer prevention and the
      role of the 2nd international science symposium on tea and human health 

PMID- 10202385
TI  - Second international scientific symposium on tea and human health: An
      introduction 

PMID- 10202387
TI  - Tea drinking and cancer risk: epidemiologic evidence 
AB  - Tea and tea compounds have been shown to inhibit carcinogenic processes in
      experimental animals, raising the possibility that tea drinking may lower cancer
      risk in humans. However, epidemiologic studies have produced inconsistent
      evidence on the relation between tea drinking and cancer risk. Ecological data
      show considerable international variation in tea consumption but relatively small
      differences in cancer rates. Results from case-control and cohort studies also
      are inconclusive. Nevertheless, high consumption of tea has been linked to a
      reduced risk of digestive tract cancers in a number of epidemiologic studies. A
      lack of detailed information on duration and amount of tea drinking, a narrow
      range of tea intake in some study populations, inadequate control for
      confounding, and potential biases in recall and reporting of tea drinking
      patterns in case-control studies may have contributed to the diverse findings.
      Further research is needed before definitive conclusions on tea's impact upon
      cancer risk in humans can be reached.

PMID- 10202388
TI  - Tea flavonols in cardiovascular disease and cancer epidemiology.
AB  - Tea is an important dietary source of flavonols in countries such as the
      Netherlands, the United Kingdom and Japan. Flavonols may have beneficial health
      effects because of their antioxidant properties and their inhibitory role in
      various stages of tumor development in animal studies. The association between
      flavonol intake and cancer risk was investigated in three prospective studies
      (Zutphen Elderly Study in the Netherlands, a Finnish cohort, and the Netherlands
      Cohort Study). Only one study (Finnish cohort) showed an inverse association with
      cancer mortality. The intake of flavonols with subsequent cardiovascular disease
      was studied in six prospective epidemiological studies. In some populations
      (Seven Countries Study, Zutphen Elderly Study, a Finnish cohort) a clear
      protective effect was observed. In a large US cohort, a protective effect was
      only found in a subgroup with previous history of coronary heart disease, whereas
      in Welsh men, flavonol intake, mainly from tea, was associated with an increased
      risk of coronary heart disease. These conflicting results may be due to
      confounding by coronary risk factors associated with tea consumption. The
      question of whether flavonols protect against cardiovascular disease remains
      still open; a protective effect of flavonols against cancer is less likely.

PMID- 10202389
TI  - Plasma and lipoprotein levels of tea catechins following repeated tea
      consumption.
AB  - Epidemiological studies suggest that antioxidant flavonoids in tea may reduce the
      risk of cardiovascular disease, possibly via protection of low-density
      lipoproteins (LDL) against oxidation. However, the extent of absorption of tea
      flavonoids and their accumulation in LDL during regular consumption of tea is not
      clear. Therefore we investigated plasma and lipoprotein levels of catechins
      during tea consumption and the impact on LDL oxidizability ex vivo. Eighteen
      healthy adults consumed, in an incomplete balanced cross-over design, green tea,
      black tea, black tea with milk or water, one cup every 2 hr (eight cups/day) for
      three days. Blood samples were obtained in the mornings and evenings of each day.
      Plasma total catechin concentration was determined in all blood samples, and the
      distribution of catechins among lipoproteins was determined at the end of the
      third day (t = 60 hr). The resistance of LDL to copper-induced oxidation ex vivo
      was assessed before tea consumption and at t = 60 hr. Repeated tea consumption
      during the day rapidly increased plasma total catechin levels whereas they
      declined overnight when no tea was consumed. There was a gradual increase in
      plasma levels in the mornings (respectively, 0.08 microM vs. 0.20 microM on first
      and last day of black tea consumption) and evenings (respectively, 0.29 microM
      vs. 0.34 microM on first and last day of black tea consumption). Green tea
      catechins were mainly found in the protein-rich fraction of plasma (60%) and in
      high-density lipoproteins (23%). Although present in LDL, the concentration of
      catechins in LDL was not sufficient to enhance the resistance of LDL to oxidation
      ex vivo. Addition of milk to black tea did not affect any of the parameters
      measured. In conclusion, the present study shows that catechin levels in blood
      rapidly increase upon repeated tea consumption. The accumulation of catechins in
      LDL particles is not sufficient to improve the intrinsic resistance of LDL to
      oxidation ex vivo.

PMID- 10202390
TI  - Preclinical efficacy studies of green and black tea extracts.

PMID- 10202391
TI  - Inhibition of carcinogenesis by tea: bioavailability of tea polyphenols and
      mechanisms of actions.

PMID- 10202392
TI  - The chemopreventive effects of tea on human oral precancerous mucosa lesions.
AB  - A double-blind intervention trial was conducted in patients with oral mucosa
      leukoplakia using a mixed tea product developed by the authors. Fifty-nine oral
      mucosa leukoplakia patients, diagnosed by established clinical and pathological
      criteria, were randomly divided into a treated group (3 g mixed tea oral
      administration and topical treatment) and a control group (placebo and glycerin
      treatment). After the 6-month trial, the size of oral lesion was decreased in
      37.9% of the 29 treated patients and increased in 3.4%; whereas the oral lesion
      was decreased in 10.0% of the 30 control patients and increased in 6.7%. At the
      same time, the incidence of micronucleated exfoliated oral mucosa cells in the
      treated group (5. 4 per 1000 cells) was lower than that in the control group
      (11.3 per 1000 cells)(P < 0.01); whereas it was 1.4 per 1000 cells in 20 healthy
      subjects. The micronuclei and chromosome aberration rate in the peripheral blood
      lymphocytes showed the same results. In pathological examination, there were
      significant differences (P < 0. 05) in the number and total volume of the silver
      stained Nucleolar Organizer Regions (AgNOR) and the proliferating index of
      Proliferation Cell Nuclear Antigen (PCNA) in oral mucosa cell nuclei between the
      treated group and the control group which indicates that cell proliferation was
      decreased in the treated patients. The overall results provide some direct
      evidence on the protective effects of tea on oral cancer.

PMID- 10202393
TI  - Mechanistic findings of green tea as cancer preventive for humans.
AB  - Based on our initial work with green tea, in which repeated topical applications
      of (-)-epigallocatechin gallate (EGCG), the main green tea polyphenol, inhibited
      tumor promotion in a two-stage carcinogenesis experiment on mouse skin (Phytother
      Res 1, 44-47, 1987), numerous scientists have since provided so much additional
      evidence of the benefits of drinking green tea that it is now an acknowledged
      cancer preventive in Japan, and will possibly soon be recognized as such in other
      countries. Our work has so far produced several important results with EGCG and
      green tea: a wide range of target organs in animal experiments for cancer
      prevention, wide bioavailability of 3H-EGCG in various organs of mice, delayed
      cancer onset of patients with a history of consuming over 10 cups of green tea
      per day, and absence of any severe adverse effects among volunteers who took 15
      green tea tablets per day (2.25 g green tea extracts, 337.5 mg EGCG, and 135 mg
      caffeine) for 6 months. This paper introduces three new findings: 1) EGCG
      interacted with the phospholipid bilayer membrane resulting in confirmation of
      the sealing effect of EGCG; 2) EGCG inhibited TNF-alpha gene expression in the
      cells and TNF-alpha release from the cells; 3) high consumption of green tea was
      closely associated with decreased numbers of axillary lymph node metastases among
      premenopausal Stage I and II breast cancer patients, and with increased
      expression of progesterone and estrogen receptors among postmenopausal ones.
      These results provide new insights into our understanding of the mechanisms of
      action of tea polyphenols and green tea extract as a cancer preventive.

PMID- 10202394
TI  - Inhibitory effect of green and black tea on tumor growth.
AB  - The administration of green tea, black tea, or (-)-epigallocatechin gallate
      inhibited the growth of established nonmalignant and malignant tumors in tumor
      bearing mice. In experiments with black tea, we found that its oral
      administration inhibited DNA synthesis and enhanced apoptosis in both
      nonmalignant and malignant tumors in tumor-bearing mice.

PMID- 10202395
TI  - Mechanism of cancer chemopreventive activity of green Tea.

PMID- 10202397
TI  - The prevention of lung cancer induced by a tobacco-specific carcinogen in rodents
      by green and black Tea.
AB  - A growing body of evidence from studies in laboratory animals indicates that
      green tea protects against cancer development at various organ sites. We have
      previously shown that green tea, administered as drinking water, inhibits lung
      tumor development in A/J mice treated with 4-(methylnitrosamino)-1-(3-pyridyl)-l
      butanone (NNK), a potent nicotine-derived lung carcinogen found in tobacco. The
      inhibitory effect of green tea has been attributed to its major polyphenolic
      compound, epigallocatechin gallate (EGCG), and, to a lesser extent, to caffeine.
      We have also demonstrated that while levels of O6-methylguanine, a critical
      lesion in NNK lung tumorigenesis, were not affected in lung DNA. However, the
      levels of 8-hydroxydeoxyguanosine (8-OH-dG), a marker of oxidative DNA damage,
      were significantly suppressed in mice treated with green tea or EGCG. These
      studies underscore the importance of the antioxidant activity of green tea and
      EGCG for their inhibitory activity against lung tumorigenesis. Unlike green tea,
      the effect of black tea on carcinogenesis has been scarcely studied, even though
      the worldwide production and consumption of black tea far exceeds that of green
      tea. The oxidation products found in black tea, thearubigins and theaflavins,
      also possess antioxidant activity, suggesting that black tea may also inhibit NNK
      induced lung tumorigenesis. Indeed, bioassays in A/J mice have shown that black
      tea given as drinking water retarded the development of lung cancer caused by
      NNK. However, data on the relationship of black tea consumption with the lung
      cancer risk in humans are limited and inconclusive. There is a need for
      additional tumor bioassays in animal models to better examine the protective role
      of black tea against lung cancer. The development of adenocarcinomas and
      adenosquamous carcinomas in F344 rats upon chronic administration of NNK provides
      an important and relevant model for lung carcinogenesis in smokers. Thus far, no
      information was previously available regarding the effects of tea on this model.
      We conducted a 2-year lifetime bioassay in F344 rats to determine whether black
      tea and caffeine are protective against lung tumorigenesis induced by NNK. Our
      studies in both mice and rats have generated important new data that support
      green and black tea and caffeine as potential preventive agents against lung
      cancer, suggesting that a closer examination of the roles of tea and caffeine on
      lung cancer in smokers may be warranted.

PMID- 10202398
TI  - The effect of tea consumption on oxidative stress in smokers and nonsmokers.
AB  - While the anticarcinogenic effects of tea in animal models have been reported by
      several groups, human epidemiological studies examining tea consumption and
      cancer prevention have produced equivocal results. The beneficial properties of
      tea to human health may be related to the antioxidant properties of tea
      components. However, little evidence has been provided that tea consumption can
      either increase the antioxidant capacity or decrease oxidative stress in humans.
      In the present study, the effects of tea treatment (green tea) on biomarkers of
      oxidative stress were investigated in smokers and nonsmokers in two volunteer
      study groups (one in China and the other in United States). Green tea consumption
      in both study groups decreased oxidative DNA damage (8-OHdG in white blood cells
      and urine), lipid peroxidation (MDA in urine), and free radical generation (2, 3
      DHBA in urine) in smokers. Nonsmokers (US study group) also exhibited a decrease
      in overall oxidative stress.

PMID- 10202396
TI  - Cancer chemopreventive mechanisms of tea against heterocyclic amine mutagens from
      cooked meat.
AB  - Cooking meat and fish under normal conditions produces heterocyclic amine
      mutagens, several of which have been shown to induce colon tumors in experimental
      animals. In our search for natural dietary components that might protect against
      these mutagens, it was found that green tea and black tea inhibit the formation
      of heterocyclic amine-induced colonic aberrant crypt foci (ACF) in the rat. Since
      ACF are considered to be putative preneoplastic lesions, we examined the
      inhibitory mechanisms of tea against the heterocyclic amines. In the initial
      studies using the Salmonella mutagenicity assay, green tea and black tea
      inhibited according to the concentration of tea leaves during brewing and the
      time of brewing; a 2-3-min brew of 5% green tea (w/v) was sufficient for >90%
      antimutagenic activity. N-hydroxylated heterocyclic amines, which are direct
      acting mutagens in Salmonella, were inhibited by complete tea beverage and by
      individual components of tea, such as epigallocatechin-3-gallate (EGCG).
      Inhibition did not involve enhanced mutagen degradation, and EGCG and other
      catechins complexed only weakly with the mutagens, suggesting electrophile
      scavenging as an alternative mechanism. Enzymes that contribute to the metabolic
      activation of heterocyclic amines, namely microsomal NADPH-cytochrome P450
      reductase and N, O-acetyltransferase, were inhibited by tea in vitro. Studies in
      vivo established that tea also induces cytochromes P450 and Phase II enzymes in a
      manner consistent with the rapid metabolism and excretion of heterocyclic amines.
      Collectively, the results indicate that tea possesses anticarcinogenic activity
      in the colon, and this most likely involves multiple inhibitory mechanisms.

PMID- 10202399
TI  - Antioxidant capacity and polyphenolic components of teas: implications for
      altering in vivo antioxidant status.
AB  - The Oxygen Radical Absorbance Capacity (ORAC) assay was used to determine the
      total antioxidant capacity of tea. Green and black teas (n = 18) had a mean
      antioxidant capacity of 761.1 +/- 85.3 micromol Trolox Equivalents (TE) per g dry
      matter. However, their antioxidant capacity varied from 235 micromol to over 1526
      micromol Trolox equivalents (TE)/g dry matter, and total phenolics ranged from 32
      to 147 mg/g in different commercial teas. One tea phenolics extract had an
      antioxidant capacity of 4796 micromol TE/g dry matter and 625 mg total
      phenolics/g. On a dry matter basis, an antioxidant capacity of 761 micromol TE/g
      is considerably higher than any of the other fruits and vegetables measured in
      our laboratory. However, since dry tea is not consumed directly, brewing
      conditions may influence the final antioxidant capacity in the tea as consumed.
      We tested both green and black teas by placing one tea bag (1.95 g) in 150 ml (5
      oz.) of boiling water. In the first brewed cup, approximately 84% of the total
      antioxidant activity was solubilized within the first 5 min of brewing. An
      additional 13% of the antioxidant activity was extracted into the second glass of
      150 ml with an additional 5 min of brewing. At the dilutions obtained after the
      first brewing, the tea as consumed would contain approximately 8. 31 micromol TE
      per ml. This total antioxidant capacity compares to other drinks from fruits and
      vegetables that had antioxidant capacity values ranging from 1.6 to 15 micromol
      TE/ml. At these antioxidant levels, consumption of 150 ml of tea could make a
      significant contribution to the total daily antioxidant capacity intake. (-)
      Epicatechin and (+)-catechin, two components from tea, had an antioxidant
      capacity of 2.36 and 2.49 micromol/micromol or 8. 13 and 8.58 micromol/mg,
      respectively. In 16 tea samples we observed a mean of 10.0 +/- 0.6 micromol TE/mg
      total phenolics. Tea can be an important source of what has been referred to as
      "non-nutrient" antioxidant phytochemicals. However, with the variation that
      exists in antioxidant capacity with various tea preparations, measures of
      antioxidant capacity intake are critical to the study of intake and health
      outcomes and/or biomarkers of health outcomes.

PMID- 10202400
TI  - Implications of the mechanisms of action of tea polyphenols as antioxidants in
      vitro for chemoprevention in humans.

PMID- 10202401
TI  - Analysis of tea polyphenols.
AB  - Tea is the most highly consumed beverage in the world, other than water. However,
      unlike water, tea contains substantial amounts of polyphenols that have unique
      biological activities and may be responsible for many of the health benefits of
      tea. As a result, it is essential to be able to measure the various tea
      associated polyphenols. Total polyphenol content is currently measured by using
      methodology based on reducing activity. Several HPLC systems with detectors that,
      collectively, have wide ranges in sensitivity have been developed for analysis of
      individual flavonoids in tea and biological samples, and for theaflavins in tea.
      Catechins also have been measured in plasma by solid phase extraction, addition
      of a chromophore, and colorimetric quantification. Except for theaflavins in tea,
      routine and robust methods for the measurement of polyphenol condensation
      products (dimers and thearubigens) in tea and biological samples have not been
      developed. Although in vitro and animal studies suggest substantial metabolism of
      flavonoids in the gastrointestinal tract, only a single HPLC procedure has been
      assembled for monitoring the metabolic products of quercetin in urine of human
      subjects.

PMID- 10202402
TI  - Tea and health: the underlying mechanisms.
AB  - Detailed multidisciplinary research on the effect of tea and the associated tea
      polyphenols has led to major advances on the underlying mechanisms. In most
      studies, green and black tea have similar effects, four of which are reviewed in
      this paper. 1) Tea polyphenols are powerful antioxidants that may play a role in
      lowering the oxidation of LDL-cholesterol, with a consequent decreased risk of
      heart disease, and also diminish the formation of oxidized metabolites of DNA,
      with an associated lower risk of specific types of cancer. 2) Tea and tea
      polyphenols selectively induce Phase I and Phase II metabolic enzymes that
      increase the formation and excretion of detoxified metabolites of carcinogens. 3)
      Tea lowers the rate of cell replication and thus the growth and development of
      neoplasms. 4) Tea modifies the intestinal microflora, reducing undesirable
      bacteria and increasing beneficial bacteria. The accumulated knowledge suggests
      that regular tea intake by humans might provide an approach to decrease the
      incidence of and mortality from major chronic diseases.

PMID- 10202403
TI  - Regional health assessment relating to mercury content of fish caught in the
      Yukon-Kuskokwim Delta rivers system.
AB  - Seven species of fish were surveyed for muscle tissue mercury content across a
      broad area of western Alaska. Total mercury levels were determined by cold vapor
      atomic fluorescence spectroscopy in 66 fish sampled during 1997. Methylmercury in
      sampled fish amounted to 97 to 100% of total mercury values. Using mercury
      consumption risk levels derived from U.S. Environmental Protection Agency hazard
      assessment models, mean total mercury was determined to be above the human
      critical value of 0.2 g/g (ppm) in 29% of the fish species, and 62% of the fish
      species contained mercury exceeding the wildlife critical value for piscivorous
      mammals. Overall, 24% of the fish exceed the critical value for human consumption
      and 58% the wildlife critical value. Similarly 31% of sites sampled exceeded the
      human consumption critical value. Based on the mean of all fish sampled and a
      small number of river otters, a biomagnification factor of 12 was calculated for
      the Yukon-Kuskokwim Delta Region of Alaska.

PMID- 10202405
TI  - Some personal reminscences about measles. Measles shots are a volatile issue-
      it's common sense.

PMID- 10202404
TI  - Antithrombotic therapy for stroke prevention among Medicare beneficiaries
      hospitalized in Alaska with atrial fibrillation.
AB  - Although warfarin therapy reduces the risk of stroke among patients with atrial
      fibrillation (AF), the risk of hemorrhagic complications and other concerns may
      make clinicians reluctant to prescribe this treatment for elderly patients.
      Aspirin is a lower-risk alternative to warfarin but is also less effective. This
      study examines the use of antithrombotic therapy with warfarin or aspirin at
      hospital discharge among 182 Medicare beneficiaries 65 or older with chronic AF
      who were admitted to nine Alaska hospitals during 1996. Sixty-five percent of
      patients without contraindications were discharged on warfarin, and an additional
      16% received aspirin. The rate of anticoagulation with warfarin was much higher
      among patients aged 65-74 (95%) than among those 75 or older (45%). The
      relatively low rate of warfarin use for very elderly patients may represent an
      opportunity to improve care. Although these patients have the highest risk of
      hemorrhagic complications, they also have the greatest potential to benefit from
      anticoagulation.

PMID- 10202406
TI  - Fiscal and patient care concerns.

PMID- 10202407
TI  - Who sets the rules on brushing?

PMID- 10202409
TI  - Practising out of province.

PMID- 10202408
TI  - Polishing.

PMID- 10202410
TI  - Practice management in dental schools--is there such a thing?

PMID- 10202411
TI  - The changing face of dentistry.

PMID- 10202412
TI  - The mediation process--the Ottawa Dental Society experience.

PMID- 10202413
TI  - Dental benefits issues and new dentists.

PMID- 10202415
TI  - Public health dentistry: 2000 to 2020.

PMID- 10202414
TI  - Design of a cast bar reinforced provisional restoration for the management of the
      interim phase in implant dentistry.
AB  - Implant therapy is becoming the treatment of choice for the replacement of teeth
      in partially edentulous arches. The interim phase of implant treatment often
      presents particular problems because of the position of the remaining teeth,
      their periodontal status, and the loss of vertical dimension of occlusion. This
      case report will discuss the design and fabrication of a cast bar reinforced long
      span provisional restoration based on a diagnostic wax-up to simplify the
      management of the interim phase.

PMID- 10202416
TI  - Death, taxes and your heirs--preserving your estate through permanent life
      insurance.

PMID- 10202417
TI  - Hot topics at AMIA. Standards, Education, and Clinical Systems.

PMID- 10202418
TI  - An interview with Jan van Bemmel. Interview by Judith Douglas.

PMID- 10202420
TI  - Standards move to center stage.

PMID- 10202419
TI  - The issues and forces that shape informatics.

PMID- 10202421
TI  - Informatics and the road to professionalism.

PMID- 10202422
TI  - Managing data in a managed care environment.
AB  - Since managed care differs from fee-for-service systems, practices should use
      this environment as an opportunity to examine their present data collection
      processes and think of the best way to integrate them into their daily
      operations. The power of marketing, financial, and quality-management data will
      be realized when managed care contract negotiations arise and when practices
      operate from a position of financial strength.

PMID- 10202423
TI  - The promise of wireless access.

PMID- 10202424
TI  - Stanford Medical Informatics: uncommon research, common goals.

PMID- 10202425
TI  - Cave art: an early example of information processing.
AB  - This article suggests that ancient cave paintings are evidence of new important
      brain functions, or "evolutionary software," that facilitated the conceptual and
      motor processes needed to create a visual scene and render it graphically.

PMID- 10202426
TI  - Increasing the acceptance of clinical information systems.

PMID- 10202427
TI  - Creating a computerized anesthesia record.

PMID- 10202428
TI  - Assessing physician's expectations and attitudes toward hospital information
      systems. The IMASIS experience.

PMID- 10202429
TI  - Using an improved back-propagation learning method to diagnose the sites of
      cardiac hypertrophy.

PMID- 10202430
TI  - Computer program for the diagnosis and treatment of polycythemia rubra vera.

PMID- 10202431
TI  - The origins of informatics.

PMID- 10202432
TI  - Boxing and the fight to ban it.

PMID- 10202433
TI  - Y2K: Missouri physicians can be prepared.

PMID- 10202434
TI  - Telemedicine beyond the technology.

PMID- 10202435
TI  - Relationship between conditional early acceptance into medical school and medical
      school leadership and academic performance: the Conley Scholar experience at the
      University of Missouri-Columbia.
AB  - The Conley Scholars Program at the University of Missouri-Columbia was created in
      1987 to guarantee top flight students entrance to medical school without the
      frantic competition well known in undergraduate pre-med programs. The program
      provides greater freedom as undergraduates than most combined baccalaureate-MD
      programs. It is not known how this freedom and avoidance of the "pre-med
      syndrome" affects medical school performance and relative leadership qualities
      compared to traditional medical students. The goals of this study are to: a)
      compare relative composition and performance of Conley medical students to
      traditional medical students; b) assess the role of Conleys in leadership
      positions within medical school organizations. METHODS: Using the medical school
      computer data files and AMCAS application files, composition, academic, and
      leadership data were collected regarding all medical school classes containing
      Conleys. Statistical analysis was performed on all data. RESULTS: The results
      suggest that: a) Conley Scholars averaged significantly higher undergraduate GPAs
      than other medical students; b) Conley Scholars averaged higher GPAs throughout
      medical school; c) Conley Scholars are more likely to hold medical school
      leadership roles than traditional medical students. CONCLUSIONS: The results
      confirm the value of the Conley Scholar Program. Benefits extend beyond academic
      achievement to encompass the development of leadership skills recognized by
      faculty and peers.

PMID- 10202436
TI  - [Intensive treatment of newborns with severe respiratory failure].

PMID- 10202437
TI  - [Thrombolytic therapy in apoplexy].

PMID- 10202438
TI  - [Thrombolytic therapy is efficient only within the first three hours after
      ischemic apoplexy].

PMID- 10202439
TI  - [Proteases and protease inhibitors in the treatment of cancer].

PMID- 10202440
TI  - [Carriers of Staphylococcus aureus as a source of nosocomial infections.
      Epidemiological and prophylactic aspects].
AB  - 20% of the normal population are nasal carriers of Staphylococcus aureus (Sa),
      and the carrier rate is even higher in insulin dependent diabetics, intravenous
      drug addicts, patients on haemo- and peritoneal dialysis, and HIV infected
      patients. Nasal Sa carriers have an increased risk of Sa infections following
      invasive therapy. Mupirocin, a novel topical antibiotic, is highly effective
      against nasal Sa. A number of studies indicate that it may reduce the incidence
      of Sa infections in dialysis patients, however experience with other categories
      of patients is sparse. Surgical wound infection with Sa is a particularly serious
      complication after implantation of foreign body material, e.g. artificial joints.
      There is a need for controlled clinical trials to test the efficacy of mupirocin
      in eradicating Sa in these types of patients. Uncritical use of mupirocin for
      topical treatment of wounds should be avoided in order to prevent development of
      resistance.

PMID- 10202441
TI  - [The first Danish experiences with neonatal extracorporeal membrane oxygenation].
AB  - In 1995, neonatal extra-corporeal membrane oxygenation (ECMO) was established at
      the Department of Neonatology, Rigshospitalet, Copenhagen. The indication for
      ECMO is circulatory or respiratory failure with arterial oxygen tension below 8
      kPa despite maximal conventional treatment. During the first two and a half years
      17 newborn infants and one child of 21 months have been treated with ECMO at the
      Rigshospital. Fifteen survived, of 12 followed at least nine months, 11 have
      normal development and one has cerebral palsy. There were problems including
      surgical placement of the cannula, technical difficulties or bleeding in 12
      patients. During the same two years at least eight newborns in Denmark fulfilled
      the ECMO indication, but were not treated, half were not transferred to the
      Rigshospital. Seven of these eight infants died. The need for ECMO treatment in
      newborn infants is documented but small. We have succeeded in establishing this
      complicated treatment due to teamwork between different specialities with a good
      result.

PMID- 10202442
TI  - [Peptic ulcer in Denmark, 1981-1993. Analysis of data from national patient
      registries].
AB  - The aim of this study was to determine whether the improvements in the treatment
      of peptic ulcers are associated with decreasing age- and sex-specific
      hospitalization and death rates for peptic ulcers in Denmark. The study was based
      on all discharges as registered in the National Hospital Discharge Registry and
      all death certificates as registered in the Danish National Board of Health from
      1981 through 1993. The age- and sex-specific and age-adjusted hospitalization and
      death rates were estimated. In women, the age-adjusted hospitalization increased
      for all types of peptic ulcers. In both sexes the age-adjusted peptic ulcer
      mortality increased mainly due to complicated duodenal ulcers. The analysis of
      the age-specific hospitalization and mortality for peptic ulcer complications
      showed that the increasing trends mainly occurred among the elderly. The improved
      medical treatment of peptic ulcers has not been associated with decreasing
      hospitalization or death from complicated peptic ulcers in Denmark.

PMID- 10202443
TI  - [Health, life style and living conditions in Greenland. The 1993-1994 Greenland
      health survey].
AB  - Existing knowledge about the disease pattern in Greenland does not include the
      Greenlanders' own perception of their health. Consequently, the Greenland Home
      Rule Government initiated a countrywide health interview survey which was carried
      out during 1993-1994. A total of 1728 adults were interviewed and filled in a
      questionnaire. Self-rated health varied with age, gender and socioeconomic
      conditions. Only few of those bothered by symptoms had contacted the health care
      services. Musculoskeletal diseases were by far the most frequent cause of
      symptoms. Suicidal thoughts were frequent; 48% had experienced the suicide of a
      relative or friend. The life style is characterized by a high consumption of
      marine mammals and fish, a decreasing but still high alcohol consumption and an
      80% prevalence of smoking among both men and women. The health care services are
      often staffed by Danish physicians and nurses. Occasionally this gives rise to
      communication problems and dissatisfaction.

PMID- 10202444
TI  - [Primary hyperoxaluria type 1 detected by liver biopsy].
AB  - PH1 is caused by deficiency of the liver-specific peroxisomal enzyme alanine:
      glycoxylate aminotransferase (AGT). Early onset with progressive renal failure
      and systemic oxalosis is typical. We report a case of a 42 year-old man with PH1
      in whom liver biopsy and DNA-analysis showed reduced AGT-activity and
      homozygosity for the polymorphism C154T and the point mutation G630A. The patient
      seems to respond to pyridoxine treatment. We suggest that clinical suspicion of
      PH1 be pursued with a diagnostic liver biopsy.

PMID- 10202445
TI  - [Highlights of research and patient treatment 1998. From the scientific
      societies].

PMID- 10202446
TI  - [New therapeutic possibilities for infertile couples, when the men suffer of
      azoospermia. The Danish Society of Obstetrics and Gynecology].

PMID- 10202447
TI  - [Treatment of gallstones].

PMID- 10202448
TI  - [Lung cancer patients and dyspnea--a therapeutic possibility].

PMID- 10202449
TI  - [One more time! Treatment of borderline primary hyperparathyroidism].

PMID- 10202450
TI  - [Morbidity from birth to death or a sick idea?].

PMID- 10202452
TI  - Evaluation of pollution prevention options to reduce styrene emissions from fiber
      reinforced plastic open molding processes.
AB  - Pollution prevention (P2) options to reduce styrene emissions, such as new
      materials and application equipment, are commercially available to the operators
      of open molding processes. However, information is lacking on the emissions
      reduction that these options can achieve. To meet this need, the U.S.
      Environmental Protection Agency's (EPA) Air Pollution Prevention and Control
      Division, working in collaboration with Research Triangle Institute, measured
      styrene emissions for several of these P2 options. In addition, the emission
      factors calculated from these test results were compared with the existing EPA
      emission factors for gel coat sprayup and resin applications. Results show that
      styrene emissions can be reduced by up to 52% by using controlled spraying (i.e.,
      reducing overspray), low-styrene and styrene-suppressed materials, and
      nonatomizing application equipment. Also, calculated emission factors were 1.6
      2.5 times greater than the mid-range EPA emission factors for the corresponding
      gel coat and resin application. These results indicate that facilities using
      existing EPA emission factors to estimate emissions in open molding processes are
      likely to underestimate actual emissions. Facilities should investigate the
      applicability and feasibility of these P2 options to reduce their styrene
      emissions.

PMID- 10202453
TI  - A statistical model for FEV1 response to arbitrary dynamic ozone exposure
      conditions.
AB  - Lung function response to inhaled ozone at ambient air pollution levels is known
      to be a function of ozone concentration, exposure duration, and minute
      ventilation. Most data-driven exposure-response models address exposures under
      static condition (i.e., with a constant ozone concentration and exercise
      pattern). Such models are simplifications, as both ambient ozone concentrations
      and normal human activity patterns change with time. The purpose of this study
      was to develop a dynamic model of response with the advantages of a statistical
      model (a relatively simple structure with few parameters). A previously proposed
      mechanistic model for changes in specific airways resistance was adapted to
      describe the percent change in forced expiratory volume in one second (FEV1).
      This model was then reduced using the fit to three existing exposure-response
      data sets as criterion. The resulting model consists of a single linear
      differential equation together with an algebraic logistic equation. Under
      restricted static conditions the model reduces to a logistic model presented
      earlier by the authors.

PMID- 10202454
TI  - Study of atmospheric ozone formation by means of a neural network-based model.
AB  - The occurrence of high ozone levels in the atmosphere of urban areas has become a
      serious pollution problem in a number of large cities in the world. Although
      mathematical models have been proposed for predicting ozone concentrations as a
      function of a number of gas components, sometimes there are uncertainties due to
      lack of the combined effects of meteorological factors and the complex chemical
      reaction system involved. The application of neural network models, based on
      measured values of air pollutants and meteorological factors at different
      locations within the Sao Paulo Metropolitan Area, combine chemical and
      meteorological information. This has shown to be a promising tool for predicting
      ozone concentration. Simulations carried out with the model indicate the
      sensitivity of ozone in relation to different air pollution and weather
      conditions. Predictions using this model have shown good agreement with measured
      values of ozone concentrations.

PMID- 10202455
TI  - Comparative study of spray booth filter system efficiency.
AB  - During recent years, greater emphasis has been placed on the control of
      particulate emissions from painting operations. This has gained more importance
      as more is learned about the potential release of toxic metals to the atmosphere
      from painting operations. This has led to queries about the efficiency of various
      painting arrestor systems to reduce particulate discharges to the atmosphere.
      Even more important is the capability of the arrestor systems to control PM10
      emissions. In 1995, the U.S. Environmental Protection Agency initiated a study to
      evaluate various dry paint overspray arrestor systems. This study was designed to
      evaluate not only the total emissions control capability of the arrestor but also
      the PM10 control capability of the various system designs. Paint overspray
      arrestor systems using five different filtration concepts or materials were
      selected. They include systems constructed of fiberglass, paper, Styrofoam, and
      cardboard materials. These systems used filtration techniques incorporating the
      following filtration phenomena and designs: cyclone, baffle, bag systems, and
      mesh systems. The testing used an optical particle counting procedure to
      determine the concentration of particles of a given size fraction to penetrate a
      test arrestor system. The results of the testing indicated that there are
      significant differences in the efficiency of the tested system designs to capture
      and retain PM10. This paper summarizes the results of the research conducted to
      determine the capability of the arrestor systems to capture particulate of sizes
      down to approximately 1 micron in surface diameter.

PMID- 10202456
TI  - Ridge augmentation for improved implant placement.
AB  - The placement of endosseous dental implants is often hampered by unfavorable
      anatomy of the alveolar bone. Guided bone regeneration and bone grafts have been
      used to reconstruct deficient alveolar ridges in preparation for dental implants.
      A case report is presented to illustrate two approaches to successful management
      of different alveolar defects.

PMID- 10202457
TI  - Treatment considerations in rapidly progressive periodontitis: a case report.
AB  - This article presents a concept for the control of periodontal pathogens in early
      onset periodontitis and demonstrates the reparative potential of periodontal
      tissue when the infection is under control. The patient discussed here was
      diagnosed with rapidly progressive periodontitis. We were able to reduce the
      bacterial mass with scaling and root planing and, in conjunction with systemic
      antibiotics, return the microbial profile to the normal range. Microbiological
      testing was used to monitor the microbiota and to adjust antimicrobial treatment.
      Improvements in probing depths and attachment levels were monitored for more than
      1 year. Tissue response to this treatment made surgical intervention unnecessary.
      Although not essential, orthodontic treatment enhanced cleansability and improved
      esthetics.

PMID- 10202458
TI  - Ridge augmentation using demineralized freeze-dried bone allograft with barrier
      membrane and cortical columns.
AB  - Ridge augmentation can be achieved with a number of approaches. Demineralized
      freeze-dried bone allograft (DFDBA) has been extensively used, often with
      controversial results. This article presents a case in which a combination of
      DFDBA, cortical columns, and expanded polytetrafluoroethylene membrane is used to
      expand a deficient ridge. After 8 months of healing, the edentulous ridge was
      successfully augmented for implant placement. Histologic and histomorphometric
      analysis of bone cores harvested from the augmented site showed new bone
      formation around the DFDBA particles and the cortical columns with lamellar bone
      formation.

PMID- 10202459
TI  - Furcation involvements: therapeutic considerations.
AB  - The successful treatment of furcation-involved multirooted teeth has been a
      challenge for many clinicians. Furcation lesions have been treated by osseous
      resection, root amputation, tooth hemisection, and other methods. Recently,
      guided tissue regeneration has been considered the treatment of choice, but
      inconsistent treatment outcomes have caused frustration for many clinicians. This
      article discusses the complexity of the furcation lesion, important aspects of
      the lesion and its relation to the tooth anatomy, and treatment options that
      should be considered.

PMID- 10202460
TI  - Esthetic restoration of anterior dentition with metal-free restorative material.

PMID- 10202461
TI  - Evaluation of a new polytetrafluoroethylene guided tissue regeneration membrane
      in healing extraction sites.
AB  - The biological principles underlying guided tissue regeneration (GTR) are
      apparently well understood, and many of the molecular events involved in bone
      regeneration are being investigated. Much controversy exists, however, as to
      which membrane biomaterial is ideal for use in these procedures. Adding to the
      confusion, new applications of GTR membranes continue to evolve, such as
      extraction site reconstruction, implant site development, ridge augmentation, and
      the use of membranes in conjunction with the placement of dental implants. These
      innovative techniques place demands on the membrane that were unforeseen when the
      first generation of devices was developed. The present study suggests that the
      ideal design characteristics of a barrier membrane, such as pore size and polymer
      type, may depend on the intended use of the membrane, and are not fixed criteria
      that should be applied to all membrane devices. This article describes the
      clinical results in a series of case studies using a high-density, microporous
      polytetrafluoroethylene membrane (Cytoplast Regentex GBR-200a). To evaluate the
      clinical efficacy of this membrane and technique, clinical and histological
      evaluation of the regenerated tissue are presented.

PMID- 10202462
TI  - Ceramic inlay fabrication with three-dimensional copy milling technology--Celay.
AB  - Efforts to improve the physical properties of ceramic materials have resulted in
      the development of restorations that are machined from preformed ceramic blocks.
      Celay is a system that uses micromilling technology to prepare these ceramic
      blocks for fabrication of inlays, onlays, veneers, and crown restorations. Celay
      restorations can be luted, using advances in composite adhesive techniques. These
      restorations are exceptionally esthetic because of a "chameleon effect," and they
      exhibit a high degree of marginal accuracy. A clinical case, included in this
      article, illustrates the technology and use of this innovative restorative
      system.

PMID- 10202463
TI  - Treating hypersensitivity with fluoride varnishes.
AB  - Dentinal hypersensitivity results when stimulation causes the fluid in open
      dentinal tubules to undergo pressure changes, which activates mechanoreceptor
      nerves and results in pain. Treatment with fluoride varnish forms a protective
      layer of calcium fluoride that prevents this fluid flow, thereby reducing
      dentinal sensitivity.

PMID- 10202464
TI  - Neuropathic orofacial pain.
AB  - Neuropathic orofacial pain (NOP) is a challenging diagnostic problem. In some
      cases, symptomatology may be similar to that seen with dental pathology,
      resulting in unwarranted dental treatment. Rarely, NOP can herald serious disease
      or central tumors, and early diagnosis can be life-saving. The following review
      outlines the classification, clinical presentation, pathophysiology, and
      treatment of the more common NOP entities.

PMID- 10202465
TI  - Lidocaine and cancer: risk or rumor?

PMID- 10202466
TI  - Evaluation of a surgical debridement bur for use in periodontal surgery.
AB  - The Evian Debridement Bur facilitates two fundamental techniques in periodontal
      surgery--soft-tissue debridement and root planing. The bur debrides granulation
      and other soft tissues attached to the root or bone and removes hard deposits
      from root surfaces. It can also be used as an adjunct while performing crown
      lengthening procedures and endodontic surgery. The bur is made with blunted
      flutes and, if used with a relatively light touch, will not cut into the alveolus
      and will not damage the tooth surface. This article reviews the use and
      advantages of this bur and shows its effect on the root surface at the
      ultrastructural level.

PMID- 10202467
TI  - Balanced force, crown-down preparation, and inject-R Fill obturation.
AB  - The balanced force concept proposes that instruments are guided by the canal
      structure when rotational motion is used. Changing the direction of rotation
      controls the probability that instruments will become overstressed and controls
      the cutting of structure to give an efficient result. Crown-down progression of
      the cleaning and shaping is possible as a result of predetermined preparations
      and use of a recent modified tip file design, the Flex-R file. Preparation time
      is minimized, while cleaning is enhanced by the crown-down approach. After
      cleaning and shaping, the intracanal aseptic state must be preserved by
      obturation. System B condensation followed by Inject-R Fill, back-filling is
      described as an efficient method to accomplish this obturation.

PMID- 10202468
TI  - Simplified obturation of tapered canal preparations.
AB  - Canals shaped to wider tapers, specifically .06 mm and .08 mm, have traditionally
      been associated with thermoplastic fills. However, the canals shaped to .06 mm
      and .08 mm tapers correlate very closely to the shape of fine-medium and medium
      gutta-percha points, respectively. Combining the placement of these single-point
      fills with the patented EZ-Fill bi-directional spiral for well-controlled
      placement of the EZ-Fill epoxy resin sealer gives the dentist the ability to
      simplify the obturation procedure with results that are at least equal to those
      achieved with lateral condensation and thermoplastic techniques.

PMID- 10202469
TI  - The time and ease of placement of the chlorhexidine chip local delivery system.
AB  - The first local delivery system for an antimicrobial agent was a nondegradable
      tetracycline-impregnated fiber introduced by Goodson et al in 1979. PerioChip, a
      biodegradable chip containing chlorhexidine, was recently approved by the Food
      and Drug Administration for the treatment of adult periodontitis. During several
      multicenter randomized clinical trials, this product, when used as an adjunct to
      scaling and root planing, was found to reduce probing depth and improve
      attachment level significantly more than scaling and root planing alone.

PMID- 10202470
TI  - Clinical applications of composite resin luting agents.

PMID- 10202471
TI  - Determination of the optimal conditions for dental subtraction radiography using
      a storage phosphor system.
AB  - OBJECTIVES: To determine the optimal kVp and exposure conditions for digital
      subtraction radiography system using a storage phosphor system. METHOD: Signal-to
      noise (SNR) measurements were acquired using a Digora system (Soredex, Helsinki,
      Finland) of large area, low contrast, clinically realistic details against
      varying degrees of background attenuation for both single exposure unsubtracted
      and subtracted images. These results were combined with a measure of estimated
      thyroid dose to derive a figure of merit (FOM) for the unsubtracted and
      subtracted images. RESULTS: For both unsubtracted and subtraction radiography, an
      exposure at 50 kVp and 250 muGy produce the best overall FOM. However, using the
      system at the 60 kVp maximum a FOM at 1000 muGy for unsubtracted radiography and
      500 muGy for subtraction radiography gave the best SNR performance. CONCLUSION:
      Operating parameters have been derived which allow the user to choose between
      optimising SNR and dose (50 kVp, 250 muGy for unsubtracted and subtracted
      radiography) or SNR alone (60 kVp, 1000 muGy for unsubtracted and 60 kVp, 500
      muGy for subtracted), for the visualisation of clinically representative details
      using the Digora system.

PMID- 10202472
TI  - Effect of noise on the compressibility and diagnostic accuracy for caries
      detection of digital bitewing radiographs.
AB  - OBJECTIVES: To determine the effect of noise on the compressibility and the
      diagnostic accuracy for caries detection of digital bitewing radiographs.
      METHODS: Bitewing radiographs of patients were obtained with a storage phosphor
      (Digora, Soredex, Helsinki, Finland) and compressed at different JPEG compression
      levels (2, 27, 53 and 128). A just noticeable difference study was performed to
      select a compression level to study the added noise effect. Gaussian noise was
      added at low, medium, and high levels to both the original and compressed images.
      Seven observers examined the selected approximal surfaces to identify the caries
      depth. ROC analysis was performed together with ANOVA at P = 0.05. RESULTS: The
      compressibility of the images decreased as the noise level increased. ROC
      analysis revealed no significant difference between the original and compressed
      images within the same noise level (P > 0.06). With added noise
      compressed/decompressed images had a higher Az than the corresponding original
      images. CONCLUSIONS: JPEG compression at level 27 can be used without a
      significant deterioration in diagnostic accuracy. Compression at this level
      seemed to reduce the effect of noise to some extent.

PMID- 10202473
TI  - Validity of computed tomography in imaging thin walls of the temporal bone.
AB  - OBJECTIVES: To evaluate the validity of computed tomography (CT) for reproduction
      of the bone margins of the temporomandibular joint (TMJ). METHODS: Seven TMJ
      specimens were examined with a CT and then cryosectioned. The bone separating the
      TMJ from the middle cranial fossa, middle ear and external auditory canal was
      measured as the full width at half maximum (FWHM). Measurements were compared
      with the true thickness of the bone wall. RESULTS: There was good agreement when
      the bone walls were thicker than 1 mm: accuracy was influenced only by the angle
      of the bone wall to the scanning plane. Conversely, bone walls thinner than 1 mm
      were reproduced with a magnification that increased with decreasing bone
      thickness. The difference increased further as the inclination of the bone wall
      became greater. CONCLUSION: Measurements performed at FWHM are reliable within +/
      10% for bone walls more than approximately 1 mm thick which form an angle of
      less than 35 degrees to the perpendicular of the scanning plane. For bone walls
      thinner than 1 mm and for those thicker than 1 mm with an inclination exceeding
      approximately 35 degrees, partial volume effects result in a progressively
      increasing magnification of bone thickness.

PMID- 10202474
TI  - Evaluation of bone density in the mandibles of young Australian adults of
      Mongoloid and Caucasoid descent.
AB  - OBJECTIVES: To evaluate the bone density in the mandibles of young Australian
      adults of Mongoloid and Caucasoid descent. METHODS: A panoramic radiograph
      (Orthophos C, Siemens AG, Bensheim, Germany) was obtained of 79 dental students
      from the School of Oral Health Sciences, The University of Western Australia.
      Exposure factors were varied for males and females. The films were automatically
      processed in a single batch and the optical density measured blindly at two
      locations by two examiners. The optical density was compared by race and sex to
      detect bone density differences. Individual lifestyle habits (exercise, alcohol
      consumption, smoking and diet) was recorded in a self-administered questionnaire.
      Multiple regression analysis was used to analyse the effects of physical,
      environmental and medical characteristics. RESULTS: The Mongoloid subjects were
      found to have approximately 20% higher bone density at the angle of mandible than
      Caucasoid subjects (P = 0.0094 for males, P = 0.0004 for females). CONCLUSION:
      Race is the most important variable associated with bone density. Mongoloid
      subjects should be given a higher exposure for panoramic radiography than that
      normally used for Caucasoid subjects.

PMID- 10202475
TI  - Performance of film, desktop monitor and laptop displays in caries detection.
AB  - OBJECTIVES: To compare film, desktop monitor and laptop displays of digitized
      film images for accuracy of caries detection. METHODS: Sixty-four extracted teeth
      were mounted in eight models and radiographed with E-speed bitewing film. Films
      were digitized and displayed on a desktop monitor and a laptop display. Six
      observers scored the presence or absence of enamel and dentinal caries for each
      proximal surface for film, desktop and laptop displays. Results were compared
      with the histology of ground sections. ROC curve areas for each display mode and
      observer were assessed for significant differences with ANOVA. RESULTS:
      Diagnostic accuracy for proximal surface caries detection was not significantly
      different for conventional film or desktop monitor and laptop displays for
      detection of enamel caries (P = 0.9112) or dentin caries (P = 0.2796).
      CONCLUSIONS: Current laptop active matrix liquid crystal displays provide
      diagnostic quality for caries detection comparable with conventional film and
      desktop monitor displays.

PMID- 10202476
TI  - Comparison of observer reliability in assessing alveolar bone changes from color
      coded with subtraction radiographs.
AB  - OBJECTIVES: To assess intra- and interobserver agreement on marginal changes in
      periodontal bone from color-coded compared with subtraction radiographs. METHODS:
      Sequential radiographs from patients undergoing periodontal treatment were
      acquired using direct digital intra-oral radiography. Fifty-one pairs of color
      coded and subtraction radiographs were produced and evaluated twice by six
      dentists for changes in marginal bone. Intra- and interobserver agreement were
      calculated. RESULTS: Intra-observer agreement was significantly higher for the
      color-coded radiographs (P < 0.05). Interobserver agreement was significantly
      higher for color-coded radiographs at the second (P < 0.001) but not the first (P
      = 0.34) evaluation. CONCLUSIONS: Color coding of radiographic differences by
      means of image addition may be a feasible alternative to the subtraction
      technique for evaluating periodontal bone changes.

PMID- 10202477
TI  - Predictability of reformatted computed tomography for pre-operative planning of
      endosseous implants.
AB  - OBJECTIVES: To determine the reliability of reformatted 2D-CT for pre-operative
      planning of implant placement. METHODS: One hundred consecutive partially or
      fully edentate patients underwent 2-D reformatted CT pre-operative planning and
      subsequent implant placement. The number, site and size of the implants, the
      available bone height and anatomical complications were recorded. The pre
      operative planning and the outcome at surgery were compared statistically using a
      percentage agreement and Kendall's correlation coefficient. RESULTS: Agreement
      between the pre- and intra-operative data was good for the number of implants
      (60%) and the selected sites (70%). From a total of 416 implants planned, 21
      implants could not be placed because of intra-operative findings. Agreement was
      relatively poor for implant size (44%) and anatomical complications (46%).
      Kendall's correlation coefficient was highest for the number of implants (0.80)
      and implant sites (0.81). It was much lower for implant sizes (0.51) and did not
      reach significance for anatomical complications (0.09). CONCLUSIONS: Reformatted
      2D-CT is reliable for the pre-operative assessment of the number and sites of
      implants in the jaws. It is less predictable for the implant size needed and poor
      for anatomical complications.

PMID- 10202478
TI  - Radiological aspects of osteosarcoma of the jaws.
AB  - OBJECTIVES: To categorize the radiological presentation of osteosarcoma of the
      jaws. METHODS: Conventional radiographs and CT scans of nine patients with
      histologically proven osteosarcoma were reviewed. RESULTS: Five patients were men
      and four women, aged between 20 and 51; four lesions were in the maxilla and five
      in the mandible. Three radiological presentations of osteosarcoma of the jaw were
      identified. The first was radiolucent, characterized by a total absence of bone
      formation within the tumour. The second had a mottled appearance with small areas
      of amorphous ossification separated by non-ossified tumour tissue. The third,
      with lamellar ossification, was typically characterized by bony plates
      irradiating from a focus like a 'sunburst'. CONCLUSION: Radiological diagnosis of
      osteosarcoma of the jaw can be difficult because of its variable appearance. CT
      is particularly useful.

PMID- 10202479
TI  - A novel panoramic machine for photofluorography.
AB  - OBJECTIVE: To describe the main features of a prototype panoramic X-ray machine
      modified for photofluorography. METHODS: The prototype PTM 2001 (Asahi Roentgen,
      Kyoto, Japan) consists of a conventional panoramic machine with a modified X-ray
      generator and incorporating a 9-inch image intensifier and a photofluorographic
      camera. RESULTS: The photofluorographic panoramic radiograph is reduced in size
      by 60% compared with conventional images. Using 10 cm x 45.7 m photoradiographic
      film 250 panoramic images can be continuously obtained. Examination time is
      shorter since cassette changes are not necessary. The radiation dose-in-air,
      measured in front of the secondary collimator, is 174 muGy. CONCLUSIONS: The
      advantages of the photofluorographic panoramic radiography include cost economy,
      shorter examination time and lower radiation exposure.

PMID- 10202480
TI  - Magnetic resonance imaging in the diagnosis of asymmetrical bilateral masseteric
      hypertrophy.
AB  - Asymmetrical bilateral masseteric hypertrophy or unilateral masseteric
      hypertrophy may present a diagnostic dilemma. While the history and clinical
      examination are important in differentiating this benign condition from parotid
      and dental pathology, they cannot necessarily exclude rarer malignant lesions of
      or within the muscle itself. We present a case where MRI provided clear and
      elegant confirmation of our provisional clinical diagnosis by illustrating both
      the soft tissue features and the logical corresponding bony features of this
      condition, thus obviating the need for further invasive investigations.

PMID- 10202481
TI  - The Digital Dental Office as the Agent of Change. A Symposium Sponsored by the
      Diagnostic Systems Group of the International Association for Dental Radiology at
      the 76th General Session. Nice, June 24-27, 1998.

PMID- 10202482
TI  - Digital diagnostic imaging: today and tomorrow.

PMID- 10202483
TI  - Standards in dental imaging.

PMID- 10202484
TI  - Decision support systems in dentistry.

PMID- 10202485
TI  - Teledentistry and the future of dental practice.

PMID- 10202486
TI  - The future of dental imaging. Where do we go from here?

PMID- 10202487
TI  - CYP enzymes and adverse drug reactions.

PMID- 10202488
TI  - Confidentiality and the curb-side consultation.
AB  - Dentists who encounter friends or relatives who request professional opinions
      about oral health problems are placed in difficult positions that may impose a
      duty to provide some advice or intervention. Even more awkward is the situation
      in which a dentist recognizes a pathosis in a nonpatient who is not seeking
      advice. The ethical principle of beneficence may confer an obligation upon the
      dentist to act in a professional role even though no professional relationship
      exists. There are criteria that guide providers in establishing that such a duty
      of specific beneficence is present; dentists must meet this duty while not
      violating the same principle of doctor-patient confidentiality that would exist
      if the nonpatient were, in fact, a patient.

PMID- 10202489
TI  - Product review: all-ceramic system.

PMID- 10202490
TI  - Regaining space by using elastic orthodontic separators.
AB  - When an extensive carious lesion is present, interproximal space may be lost due
      to drifting of adjacent teeth. This may encroach upon the space needed to restore
      the tooth to proper occlusal and interproximal contours. Although the space may
      be regained with conventional orthodontics, this may not be an option in some
      cases due to financial or technical considerations. The outlined clinical
      technique uses elastic orthodontic separators in conjunction with an
      incrementally modified acrylic crown to regain lost interproximal space. The
      results of this technique were achieved rapidly and allowed for the placement of
      a physiologically contoured restoration. This procedure is technically simple,
      provides quick results, and is less expensive for the patient than conventional
      orthodontics.

PMID- 10202491
TI  - Functional appliances and functional regulators.
AB  - Patients with dental malocclusions and facial-skeletal problems often have
      unattractive facial and dental features that can create social and emotional
      problems such as lack of self-confidence and poor self-image. In addition, a
      number of medical problems are associated with facial-skeletal disharmonies.
      Here, we review three functional appliances--the Schwarz, Bionator, and Frankel
      III --that can be used to correct dental and facial-skeletal problems.

PMID- 10202492
TI  - Are latex gloves a contributing cause of percutaneous injury in dentists?
AB  - Fifty dentists were examined to determine if (and how) latex gloves contributed
      to percutaneous injury, the leading cause of occupational AIDS/HIV transmission
      in health care workers. Latex glove wear is closely associated with a 16-fold
      increase in percutaneous injury with endodontic file manipulation than when
      subjects were tested barehanded. Dynamometer tests showed a 36 percent decrease
      in light-touch proprioception in subjects when they were gloved as compared to
      scores when they were tested barehanded. A 28 percent glove-related dermatitis
      rate among test subjects is also reported.

PMID- 10202493
TI  - Guidelines for using posts in the restoration of endodontically treated teeth.
AB  - A review of the literature was done to determine when posts are required for
      restoring endodontically treated teeth and to give guidance on preparation of
      post space, design of posts, and use of luting agents. Posts were deemed to be
      unnecessary when adequate coronal tooth structure was present to retain a core.
      It was found that tooth structure should not be removed to construct a stronger
      post. The thinnest post with adequate strength was recommended. For best
      retention, it was found that post surfaces should not be smooth. When resin
      reinforced glass ionomer cements were used, they were found to be potentially
      harmful to restored teeth. Remaining coronal tooth structure was found to have
      the highest correlation in regard to success of the final restoration of
      endodontically treated teeth.

PMID- 10202494
TI  - A review of endodontic medicaments.
AB  - Endodontic intracanal medicaments are often used when root canal therapy cannot
      be completed in a single visit. Properties of the more commonly used medicaments
      are outlined, their effectiveness is examined, and recommendations for use are
      made, based on evidence in the literature reviewed here.

PMID- 10202495
TI  - A review of localized juvenile periodontitis (LJP): Part I. Clinical features,
      epidemiology, etiology, and pathogenesis.
AB  - Localized juvenile periodontitis (LJP) is not commonly encountered in dental
      practice. Yet, when it is encountered, prompt and effective therapy is required
      to combat the severity of disease and its rapid progression. Failure to
      understand its diagnosis and etiology leads to failures in management of LJP. The
      clinical features, etiology, and pathogenesis of LJP are reviewed to provide the
      clinician with a sufficient understanding to appropriately manage or refer LJP
      patients.

PMID- 10202496
TI  - Prevention of white spot enamel formation during orthodontic treatment.
AB  - Orthodontic therapy is a much needed and desired treatment of dental service.
      However, when patient oral hygiene performance is inadequate, undesirable white
      spot enamel lesions can appear. If unchecked, they may progress to frank caries.
      The various etiological factors are discussed and preventive strategies are
      proposed to combat such lesions. This information will help specialists and
      general dentists alike to better predict, diagnose, and prevent these lesions
      while providing active orthodontic treatment.

PMID- 10202498
TI  - The American Heart Association's guidelines for the prevention of bacterial
      endocarditis: a critical review.
AB  - Since 1955, the American Heart Association (AHA) has made eight recommendations
      regarding the prevention of bacterial endocarditis. The most recent guidelines
      were published in 1997. Presented here is a review of the AHA recommendations,
      with emphasis on the 1997 guidelines. The new recommendations list the medical
      conditions that require antibiotic prophylaxis, expand the number of dental
      procedures that do not require prophylaxis, and present single-dose regimens for
      use in patients who are susceptible to bacterial endocarditis. These single-dose
      oral regimens should lead to increased compliance by dentists and patients.

PMID- 10202497
TI  - The telephone: your office shouldn't sound like your local plumbing supply.
AB  - The manner of use of the telephone plays a significant role in the quality of
      care given to dental patients. Good telephone techniques, both in general and in
      responding to complaints, affect how a dentist is evaluated by his or her
      patients.

PMID- 10202499
TI  - One-appointment composite crown: an alternative to conventional crown and bridge.
AB  - When presented with little coronal tooth structure remaining, four options exist:
      (1) extraction only, (2) extraction and restoration, (3) root canal therapy and a
      cast restoration (which may involve crown lengthening and/or orthodontic
      extrusion), or (4) root canal therapy and a composite/amalgam crown. A technique
      for the composite crown option is described with case presentations.

PMID- 10202500
TI  - Clinical profile of ameloblastoma among Filipino patients in Metro Manila
      hospitals.
AB  - A retrospective study was made on Filipino patients having Ameloblastoma. The
      clinical records showed a total of 177 patients diagnosed and treated with
      Ameloblastoma from the six Metro Manila Hospitals. Ages of patients ranged from
      less than 9 years old to over 60 years old. The data showed that Ameloblastoma
      occurred frequently among patients during the second decade of life in both
      sexes. The right side of the mandible at the molar ramus area is the most
      frequent site of occurrence to both sexes. In majority of the cases the patients
      sought consultation when the tumor was quite extensive. Most of the cases were
      treated by mandibular resection or hemimandibulectomy.

PMID- 10202501
TI  - An assessment of professionalism among Metro Manila dentists.

PMID- 10202502
TI  - Pathologic changes associated with the angulation of impacted mandibular third
      molars.
AB  - A nine-month clinical and radiographic survey was done on 337 impacted mandibular
      third molar hospital cases to determine the incidence of caries, alveolar bone
      loss, and adjacent tooth material loss and the relation of the angulation of the
      third molar. Sixty percent of the cases was affected by any one of the three
      pathologic changes; however, individually each lesion registered rates at 42% or
      lower. The mesioangular orientation registered the highest incidence rates among
      the four and contributed the most lesions when compared to the four. The majority
      of mesioangular cases had all three lesions. Thus the presence of the impacted
      mesioangular third molar should heighten the advocacy for its removal.

PMID- 10202503
TI  - Malignant fibrous histiocytoma of the maxilla: a case report.
AB  - Malignant fibrous histiocytoma is one of the most common sarcomas of soft tissues
      in late adult life. However, this neoplasm rarely arises in the oral and
      maxillofacial region with the maxilla presenting as an unusual site. A case
      report of a 40-year old woman with malignant fibrous histiocytoma involving the
      maxilla is discussed with relevant literature reviewed. The treatment chosen was
      partial maxillectomy. The patient was referred for cobalt therapy after surgery.
      Eight months after diagnosis, the patient died of the illness.

PMID- 10202504
TI  - Professionalism: the key to leadership in the dental profession.

PMID- 10202505
TI  - A study on the potentials of popular literature as health education materials.

PMID- 10202506
TI  - Gingival degerming by povidone-iodine irrigation: bacteremia reduction in
      extraction procedures.
AB  - The purpose of this study was to find out whether or not a certain mouth wash,
      i.e. povidone-iodine, will reduce the incidence of bacteremia following tooth
      extraction. The sample was composed of twenty-six patients who were given
      gingival sulcus irrigation and rinsing prior to tooth extraction. Thirteen
      patients used povidone-iodine mouthwash and the other 13 patients with an
      identically matched placebo. Prior to irrigation and rinse, first blood sample is
      drawn and first gingival sulcus sample is taken. To complete the whole procedure,
      the patient rinsed with 10-20 ml of assigned coded mouthwash for 30 seconds and
      then repeated the rinsing after 2 minutes followed by 60 second irrigation with
      10-20 ml of the same coded mouthwash, administered in the gingival sulcus and
      surrounding mucosa of the tooth to be extracted. A second gingival sulcus sample
      is taken then extraction is performed. A second blood sample is drawn within 3
      minutes of extraction. Growth and reduction in bacteremia were determined before,
      during and after extraction procedure. Results indicated significant reduction in
      incidence of post-operative bacteremia with povidone-iodine as compared with
      placebo (P = .01558) and significant reduction in growth of gingival cultures
      with povidone iodine as compared with placebo (= .65337). Povidone-iodine
      mouthwash used as a rinse and gingival sulcus irrigant reduced the growth of
      gingival cultures and the incidence of post-operative bacteremia in more specimen
      compared to the placebo.

PMID- 10202507
TI  - Getting our acts together: for oral health.

PMID- 10202508
TI  - Open reduction with rigid internal fixation using an eccentric dynamic
      compression plate for a displaced angle fracture of the mandible in a patient
      with previous anterior crossbite.

PMID- 10202509
TI  - Sequencing of treatments in the insertion of multiple implants in a very damaged
      alveolar ridge.

PMID- 10202510
TI  - Emergency management of epistaxis: a case report and review of principles.

PMID- 10202511
TI  - Algorithm for the management of oral pathologic lesions.
AB  - The detection of an Oral Pathologic Lesion may leave the General Practitioner in
      a state of perplexity! This paper will present a simple and logical approach to
      the clinical decisions in managing that problem.

PMID- 10202512
TI  - Oral health status of institutionalized geriatric residents in Metro Manila.
AB  - A study was done on geriatric residents from three institutions in Metro Manila
      namely La Verna I and II, a retirement home of Sisters of Franciscan Immaculate
      Concepcion; Hospicio de San Jose, a catholic welfare institution for the very
      young as well as for the very old; and Golden Acres, a government institution
      that takes care of indigent old/elderly people. A total of 176 geriatric
      residents were examined, majority are from Golden Acres with 121, followed by
      Hospicio de San Jose with 30 and lastly La Verna I and II with 25. In general,
      the oral health status of geriatric residents is very poor especially at Golden
      Acres and Hospicio de San Jose. Since all the resident sisters in La Verna I and
      II are highly educated, their oral health status is fair to good. The more
      prevalent medical problems the geriatric residents had are: Cataract (54);
      Hypertension/Cardiac Disorders (46); Rheumatoid Arthritis (30); Respiratory
      Diseases (29); Blood Diseases (28); Diabetes Mellitus (14); Skin Diseases (10);
      Impaired Hearing (13); Neurologic Problems (19); and Psychological Problems (2).

PMID- 10202513
TI  - Extraoral maxillary and mandibular nerve blocks for a patient with Sutton's
      disease.

PMID- 10202514
TI  - Management of mandibular fascial space infection of odontogenic origin.
AB  - Cellulitis is an acute, painful infection whose swelling is larger with diffuse
      borders. When palpated, early cellulitis can be very soft or doughfy; a severe
      cellulitis is almost always described as indurated or even as being "board-like".
      It can be innocuous in its early stages and extremely dangerous in its more
      advance, indurated, rapidly spreading stages. Randy, a 16 years old boy who
      thought that a regularly occurring toothache can advance into a life-threatening
      complication has a lot to be thankful for. The patient was referred to the
      Pediatric Dentistry Division by the E.R. doctors for further evaluation and
      management due to a swelling on the lower quadrant of his face. This was on the
      8th day after he experienced the first pain on tooth no. 47.

PMID- 10202515
TI  - Cystic management in a 10-year old child.
AB  - Cysts are among the most common lesions found in the oral cavity. These may be
      developmental in origin or secondary to chronic infections. Untreated, cysts may
      expand causing local tissue destruction and deformities. Basically, two treatment
      methods are employed. Enucleation and/or Marsupialization. The following case
      involves a child treated at the College of Dentistry, University of the
      Philippines, for a large cystic lesion involving the permanent cuspid and the
      deciduous dentition. The lesion was accidentally discovered on a panoramic
      radiograph. The child underwent extraction of deciduous teeth and
      marsupialization, which later helped in the eruption of the malposed permanent
      teeth.

PMID- 10202516
TI  - Management of bruxism.

PMID- 10202517
TI  - A comparative study of the upper and lower vertical facial measurements of the
      Filipinos as it is used in the Willis method for determining the vertical
      dimension of occlusion.
AB  - 'Willis' methods is one of the methods used to determine the vertical dimension
      of occlusion, where the upper facial height from the pupil of the eye to the rima
      oris, is presumed to be equal to the lower facial height, which is the vertical
      measurement from the base of the nose to the lower border of the chin, when the
      teeth are in occlusion. Results of this study shows that the two measurements are
      not equal. The upper facial measurement is longer than the lower facial
      measurements by 3 cm.

PMID- 10202518
TI  - Team building: a leadership strategy.
AB  - This paper will present the importance of teamwork, as well as those behavioral
      science principles relative to team-building in an organization. Characteristics
      of an effective work team and some important dimensions of supervisory leadership
      including inputs on how members of a task group can contribute to team-building
      will be described. Some guidelines for supervisors and employees in connection
      with teamwork will be discussed. Human beings of every age are finding their time
      consumed by the demands of organizations to which they "belong" and still are
      badgered to join other groups during a lifetime. In the International College of
      Dentists, Philippine Section, where we pride ourselves to be a part of,
      membership is defined. We are supposed to be endowed with group consciousness, a
      sense of purpose, an interaction among ourselves, and interdependence in the
      satisfaction of our needs in a unitary manner. In essence, we are linked by some
      common, identifiable characteristics bound by the element of teamwork for the
      achievement of a common desirable goal. A leadership style that emphasizes team
      building, therefore ensures not only that a job gets done, but it is done
      efficiently, effectively and harmoniously.

PMID- 10202519
TI  - Three years in the awards committee.

PMID- 10202520
TI  - Endodontic needs of geriatric patients in private practice.
AB  - Twenty-five (25) teeth of fifteen (15) elderly patients endodontically treated in
      a private clinic for the span of three (3) years were evaluated in terms of
      success and failure of treatment. The attitudes of the patients towards
      endodontics were determined. Also, medical, dental and radiographic records were
      reviewed. Of the fifteen (15) patients. 53.3% belonged to age group 60 to 69
      years old and the other half belonged to the 70 years and above age bracket.
      Majority were female, married and college graduates. Premolars constituted 40% of
      the teeth treated. Post, core and PFM crowns were the most common restoration for
      both anterior and posterior teeth. Success rate of root canal treatment was a
      high 84%. Patients gave a more positive attitude to the endodontic treatment
      mentioning relief of pain, appreciation of better food and self-esteem.
      Calcification was the most common problem encountered during the treatment.
      Quality radiograph, proper instrumentation, appropriate techniques and chemical
      adjuncts are recommended. Likewise, proper patient management, needed rapport and
      patience have to be stressed.

PMID- 10202521
TI  - Community participation in dental health.

PMID- 10202522
TI  - Geriatric dentistry: concern of the future.

PMID- 10202523
TI  - Cephalosporins: its use in dentistry.

PMID- 10202524
TI  - Comparative study of dimensional accuracy of different impression techniques
      using addition silicone impression material.
AB  - This study compared dimensional accuracy of the single, double with spacer,
      double with cut-out and double mix impression technique using addition silicone
      impression material. A typhodont containing Ivorine teeth model with six (6) full
      crown tooth preparations were used as the positive control. Two stone replication
      models for each impression technique were made as test materials. Accuracy of the
      techniques were assessed by measuring four dimensions on the stone dies poured
      from the impression of the Ivorine teeth model. Results indicated that most of
      the measurements for the height, width and diameter slightly decreased and a few
      increased compared with the Ivorine teeth model. The double with cut-out and
      double mix technique presents the least difference from the master model as
      compared to the two latter impression techniques.

PMID- 10202525
TI  - A new California law and its impact on foreign-trained dentists.

PMID- 10202526
TI  - 138 cases of mandibular fractures in four government hospitals from July 1995 to
      July 1996.
AB  - A descriptive type of study was utilized in the presentation of this paper. The
      main sources of information were the different government hospitals namely, East
      Avenue Medical Center, Jose R. Reyes Memorial Hospital, Philippine Orthopedic
      Hospital, and V. Luna Memorial Hospital. This paper was based on information
      gathered from actual cases and medical records of the patients treated in the
      above mentioned government hospitals from July 1995 to July 1996. The results of
      the study sample shows that 117 (84.8%) males were affected. The major cause of
      mandibular fracture was alleged assaults or mauling comprising 60 (43.5%) cases
      of the entire study. The symphysis was the part of the mandible most susceptible
      to fracture having 75 (54%) cases of the study.

PMID- 10202527
TI  - Experimental Biology 99. Washington, DC, USA. April 17-21, 1999. Abstracts, Part
      I.

PMID- 10202528
TI  - Experimental Biology 99. Washington, DC, USA. April 17-21, 1999. Abstracts, Part
      II.

PMID- 10202529
TI  - Monitoring secretory membrane with FM1-43 fluorescence.
AB  - FM1-43 and similar styryl dyes have proven useful as probes for membrane
      trafficking because they reversibly stain membranes, are impermeable to
      membranes, and are more fluorescent when bound to membranes than when in
      solution. Because these dyes stain membranes in an activity-dependent manner,
      they are ideal for studies of neurotransmitter release mechanisms such as
      synaptic vesicle recycling, exocytosis, and endocytosis. FM dyes have been used
      in conjunction with other techniques such as fluorescent calcium indicator dyes
      and electrophysiological techniques to elucidate mechanisms of presynaptic
      calcium homeostasis and modulation of neurotransmitter release. Presynaptic
      membranes have been marked by FM dyes in studies of synaptogenesis and
      reinnervation. As a probe for endocytosed membranes, these dyes have been used to
      examine vacuole formation in yeast. These versatile membrane dyes are useful in a
      variety of applications.

PMID- 10202530
TI  - The cell biology of the blood-brain barrier.
AB  - The blood-brain barrier (BBB) is formed by brain capillary endothelial cells
      (ECs). In the late embryonic and early postnatal period, these cells respond to
      inducing factors found in the brain environment by adopting a set of defined
      characteristics, including high-electrical-resistance tight junctions. Although
      the factors have not been identified definitively, a great deal of information
      about brain ECs has been obtained, especially recently. This review concentrates
      on a cell biological analysis of the BBB, with an emphasis on regulation of the
      specialized intercellular junctions. The development of these junctions seems to
      depend on two primary processes: the appearance of high levels of the tight
      junction protein occludin and intracellular signaling processes that control the
      state of phosphorylation of junctional proteins. Recent studies have revealed
      that the BBB can be modulated in an ongoing way to respond to environmental
      stimuli.

PMID- 10202531
TI  - Retinal waves and visual system development.
AB  - Many pathways in the developing visual system are restructured and become highly
      organized even before vision occurs. Yet the developmental processes underlying
      the remodeling of visual connectivity are crucially dependent on retinal
      activity. Surprisingly, the immature and light-insensitive retina spontaneously
      generates a pattern of rhythmic bursting activity during the period when the
      connectivity patterns of retinal ganglion cells are shaped. Spatially, the
      activity is seen to spread across the retina in the form of waves that bring into
      synchrony the bursts of neighboring cells. Waves are present in the developing
      retina of higher and lower vertebrates, which suggests that this form of activity
      may be a common and fundamental mechanism employed in the activity-dependent
      refinement of early patterns of visual connections. Unraveling the cues encoded
      by the waves promises to provide important insights into how interactions driven
      by specific patterns of activity could lead to the modification of connectivity
      during development.

PMID- 10202532
TI  - Making brain connections: neuroanatomy and the work of TPS Powell, 1923-1996.
AB  - Dr. Thomas PS Powell was one of the founders of modern neuroanatomy. His career
      spanned an era that saw techniques for analyzing connections in the central
      nervous system dramatically increase in number and resolving power. In tracing
      the history of his research, one can see how the introduction of each new
      technique provided an incremental step in analytical capacity although eventually
      revealing its own limitations. Also evident is the extent to which prejudices
      born in the days of applying earlier techniques could continue to influence the
      interpretation of results obtained with new ones. Powell's contributions to
      neuroscience were extremely wide-ranging, encompassing investigations of the
      circuitry of the basal ganglia, corticofugal connections, topographic maps in
      sensory systems, central olfactory pathways, corticocortical and commissural
      connections, and pathways for sensory convergence in the cerebral cortex. From
      these investigations, made with tract tracing techniques, much existing knowledge
      of forebrain organization is derived. He was also one of the earliest
      investigators to use electron microscopy in the investigation of the central
      nervous system, and his electron microscopic studies on the olfactory bulb,
      thalamus, cerebral cortex, and basal ganglia laid, to a large extent, the
      foundations for all modern research on the synaptic circuitry of these
      structures. He was given to synthesizing data across systems in order to arrive
      at common principles of brain organization. A number of these syntheses have been
      sources of great interest and, occasionally, controversy.

PMID- 10202533
TI  - Stress and hippocampal plasticity.
AB  - The hippocampus is a target of stress hormones, and it is an especially plastic
      and vulnerable region of the brain. It also responds to gonadal, thyroid, and
      adrenal hormones, which modulate changes in synapse formation and dendritic
      structure and regulate dentate gyrus volume during development and in adult life.
      Two forms of structural plasticity are affected by stress: Repeated stress causes
      atrophy of dendrites in the CA3 region, and both acute and chronic stress
      suppresses neurogenesis of dentate gyrus granule neurons. Besides
      glucocorticoids, excitatory amino acids and N-methyl-D-aspartate (NMDA) receptors
      are involved in these two forms of plasticity as well as in neuronal death that
      is caused in pyramidal neurons by seizures and by ischemia. The two forms of
      hippocampal structural plasticity are relevant to the human hippocampus, which
      undergoes a selective atrophy in a number of disorders, accompanied by deficits
      in declarative episodic, spatial, and contextual memory performance. It is
      important, from a therapeutic standpoint, to distinguish between a permanent loss
      of cells and a reversible atrophy.

PMID- 10202534
TI  - Etiology and pathogenesis of Parkinson's disease.
AB  - Parkinson's disease (PD) is an age-related neurodegenerative disorder that
      affects approximately 1 million persons in the United States. It is characterized
      by resting tremor, rigidity, bradykinesia or slowness, gait disturbance, and
      postural instability. Pathological features include degeneration of dopaminergic
      neurons in the substantia nigra pars compacta coupled with intracytoplasmic
      inclusions known as Lewy bodies. Neurodegeneration and Lewy bodies can also be
      found in the locus ceruleus, nucleus basalis, hypothalamus, cerebral cortex,
      cranial nerve motor nuclei, and central and peripheral components of the
      autonomic nervous system. Current treatment consists of a dopamine replacement
      strategy using primarily the dopamine precursor levodopa. While levodopa provides
      benefit to virtually all PD patients, after 5-10 years of treatment the majority
      of patients develop adverse events in the form of dyskinesia (involuntary
      movements) and fluctuations in motor response. Further, disease progression is
      associated with the development of dementia, autonomic dysfunction, and postural
      instability, which do not respond to levodopa therapy. Accordingly, research
      efforts have been directed toward understanding the etiology and pathogenesis of
      PD in the hope of developing a more effective therapy that will slow or halt the
      natural progression of PD. This paper reviews recent advances.

PMID- 10202535
TI  - Computational neuroimaging of human visual cortex.
AB  - Functional magnetic resonance imaging is a new neuroimaging method for probing
      the intact, alert, human brain. With this tool, brain activity that has been
      hidden can now be measured. Recent advances in measuring and understanding human
      neural responses underlying motion, color, and pattern perception are reviewed.
      In individual human brain, we can now identify the positions of several
      retinotopically organized visual areas; measure retinotopic organization within
      these areas; identify the location of a motion-sensitive region in individual
      brains; measure responses associated with contrast, color, and motion; and
      measure effects of attentional modulation on visually evoked responses. By
      framing experiments and analyses as questions about visual computation, these
      neuroimaging measurements can be coupled closely with those from other basic
      vision-science methods.

PMID- 10202536
TI  - Autoimmunity and neurological disease: antibody modulation of synaptic
      transmission.
AB  - Over the past three decades, compelling evidence has emerged that the immune
      system can attack the nervous system with devastating consequences for human
      health. Either cell-mediated or humoral (antibody-mediated) autoimmune mechanisms
      may predominate in effecting a given disease, and either glia or neurons may fall
      under immune attack. A subset of these diseases has been particularly useful for
      understanding fundamental neuroscience as well as mechanisms of human disease.
      This subset involves humoral autoimmune attack on cell surface molecules
      subserving transmembrane signaling of excitable cells; special emphasis is placed
      here on proteins involved in synaptic transmission. We begin by reviewing the
      prototypic humoral autoimmune disease of synaptic transmission, myasthenia
      gravis. This provides a context for insights obtained from the study of diseases
      targeting molecules that regulate synaptic transmission at the neuromuscular
      junction and in the central nervous system. We also explore a disease where
      autoimmunity produces agonist antibodies acting at two distinct G-protein-coupled
      receptors. We conclude with an exploration of the vital issue of access of
      antibodies to targets within the central nervous system and the implications that
      such access may have in the pathogenesis of poorly understood idiopathic central
      nervous system diseases.

PMID- 10202538
TI  - Microglia as mediators of inflammatory and degenerative diseases.
AB  - Microglia are the principal immune cells in the central nervous system (CNS) and
      have a critical role in host defense against invading microorganisms and
      neoplastic cells. However, as with immune cells in other organs, microglia may
      play a dual role, amplifying the effects of inflammation and mediating cellular
      degeneration as well as protecting the CNS. In entities like human
      immunodeficiency virus (HIV) infection of the nervous system, microglia are also
      critical to viral persistence. In this review we discuss the role of microglia in
      three diseases in which their activity is at least partially deleterious: HIV,
      multiple sclerosis, and Alzheimer's disease.

PMID- 10202537
TI  - Monoamine oxidase: from genes to behavior.
AB  - Cloning of MAO (monoamine oxidase) A and B has demonstrated unequivocally that
      these enzymes are made up of different polypeptides, and our understanding of MAO
      structure, regulation, and function has been significantly advanced by studies
      using their cDNA. MAO A and B genes are located on the X-chromosome (Xp11.23) and
      comprise 15 exons with identical intron-exon organization, which suggests that
      they are derived from the same ancestral gene. MAO A and B knock-out mice exhibit
      distinct differences in neurotransmitter metabolism and behavior. MAO A knock-out
      mice have elevated brain levels of serotonin, norephinephrine, and dopamine and
      manifest aggressive behavior similar to human males with a deletion of MAO A. In
      contrast, MAO B knock-out mice do not exhibit aggression and only levels of
      phenylethylamine are increased. Mice lacking MAO B are resistant to the
      Parkinsongenic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine. Both
      MAO A and B knock-out mice show increased reactivity to stress. These knock-out
      mice are valuable models for investigating the role of monoamines in psychoses
      and neurodegenerative and stress-related disorders.

PMID- 10202539
TI  - Neural selection and control of visually guided eye movements.
AB  - We review neural correlates of perceptual and motor decisions, examining whether
      the time they occupy explains the duration and variability of behavioral reaction
      times. The location of a salient target is identified through a spatiotemporal
      evolution of visually evoked activation throughout the visual system. Selection
      of the target leads to stochastic growth of movement-related activity toward a
      fixed threshold to generate the gaze shift. For a given image, the neural
      concomitants of perceptual processing occupy a relatively constant interval so
      that stochastic variability in response generation introduces additional
      variability in reaction times.

PMID- 10202540
TI  - The specification of dorsal cell fates in the vertebrate central nervous system.
AB  - The generation of distinct classes of neurons at defined positions within the
      developing vertebrate nervous system depends on inductive signals provided by
      local cell groups that act as organizing centers. Genetic and embryological
      studies have begun to elucidate the processes that control the pattern and
      identity of neuronal cell types. Here we discuss the cellular interactions and
      molecular mechanisms that direct neuronal cell fates in the dorsal half of the
      vertebrate central nervous system. The specification of dorsal neuronal cell
      fates appears to depend on a cascade of inductive signals initiated by cells of
      the epidermal ectoderm that flank the neural plate and propagated by roof plate
      cells within the neural tube. Members of the transforming growth factor-beta (TGF
      beta) family of secreted proteins have a prominent role in mediating these
      dorsalizing signals. Additional signals involving members of the Wnt and
      fibroblast growth factor (FGF) families may also contribute to the proliferation
      and differentiation of dorsal neuronal cell types.

PMID- 10202541
TI  - Neurotrophins and synaptic plasticity.
AB  - Despite considerable evidence that neuronal activity influences the organization
      and function of circuits in the developing and adult brain, the molecular signals
      that translate activity into structural and functional changes in connections
      remain largely obscure. This review discusses the evidence implicating
      neurotrophins as molecular mediators of synaptic and morphological plasticity.
      Neurotrophins are attractive candidates for these roles because they and their
      receptors are expressed in areas of the brain that undergo plasticity, activity
      can regulate their levels and secretion, and they regulate both synaptic
      transmission and neuronal growth. Although numerous experiments show demonstrable
      effects of neurotrophins on synaptic plasticity, the rules and mechanisms by
      which they exert their effects remain intriguingly elusive.

PMID- 10202542
TI  - Space and attention in parietal cortex.
AB  - The space around us is represented not once but many times in parietal cortex.
      These multiple representations encode locations and objects of interest in
      several egocentric reference frames. Stimulus representations are transformed
      from the coordinates of receptor surfaces, such as the retina or the cochlea,
      into the coordinates of effectors, such as the eye, head, or hand. The
      transformation is accomplished by dynamic updating of spatial representations in
      conjunction with voluntary movements. This direct sensory-to-motor coordinate
      transformation obviates the need for a single representation of space in
      environmental coordinates. In addition to representing object locations in
      motoric coordinates, parietal neurons exhibit strong modulation by attention.
      Both top-down and bottom-up mechanisms of attention contribute to the enhancement
      of visual responses. The saliance of a stimulus is the primary factor in
      determining the neural response to it. Although parietal neurons represent
      objects in motor coordinates, visual responses are independent of the intention
      to perform specific motor acts.

PMID- 10202543
TI  - Growth cone guidance: first steps towards a deeper understanding.
AB  - Growth cones, the hand-like structures at the tip of growing neurites, possess
      remarkable abilities to detect directional cues. On their way to their targets
      they traverse a dense jungle of many different cells, expressing a variety of
      different molecular guidance cues. Proper reading and integration of these cues
      is essential for precise wiring of different parts of the peripheral and central
      nervous systems. Guidance cues have been classified according to the response
      they elicit as either attractive or repulsive. Recent work, however, suggests
      that this might not represent an absolute distinction and that the internal state
      of the growth cone can dictate whether it detects a cue as repulsive or
      attractive. This article reviews some new experimental approaches to
      understanding growth cone signal transduction mechanisms induced by extracellular
      guidance cues.

PMID- 10202544
TI  - Development of the vertebrate neuromuscular junction.
AB  - We describe the formation, maturation, elimination, maintenance, and regeneration
      of vertebrate neuromuscular junctions (NMJs), the best studied of all synapses.
      The NMJ forms in a series of steps that involve the exchange of signals among its
      three cellular components--nerve terminal, muscle fiber, and Schwann cell.
      Although essentially any motor axon can form NMJs with any muscle fiber, an
      additional set of cues biases synapse formation in favor of appropriate partners.
      The NMJ is functional at birth but undergoes numerous alterations postnatally.
      One step in maturation is the elimination of excess inputs, a competitive process
      in which the muscle is an intermediary. Once elimination is complete, the NMJ is
      maintained stably in a dynamic equilibrium that can be perturbed to initiate
      remodeling. NMJs regenerate following damage to nerve or muscle, but this process
      differs in fundamental ways from embryonic synaptogenesis. Finally, we consider
      the extent to which the NMJ is a suitable model for development of neuron-neuron
      synapses.

PMID- 10202545
TI  - Presynaptic ionotropic receptors and the control of transmitter release.
AB  - The quantity of neurotransmitter released into the synaptic cleft, the
      reliability with which it is released, and the response of the postsynaptic cell
      to that transmitter all contribute to the strength of a synaptic connection. The
      presynaptic nerve terminal is a major regulatory site for activity-dependent
      changes in synaptic function. Ionotropic receptors for the inhibitory amino acid
      GABA, expressed on the presynaptic terminals of crustacean motor axons and
      vertebrate sensory neurons, were the first well-defined mechanism for the
      heterosynaptic transmitter-mediated regulation of transmitter release. Recently,
      presynaptic ionotropic receptors for a large range of transmitters have been
      found to be widespread throughout the central and peripheral nervous systems. In
      this review, we first consider some general theoretical issues regarding whether
      and how presynaptic ionotropic receptors are important regulators of presynaptic
      function. We consider the criteria that should be met to identify a presynaptic
      ionotropic receptor and its regulatory function and review several examples of
      presynaptic receptors that meet at least some of those criteria. We summarize the
      classic studies of presynaptic inhibition mediated by GABA-gated Cl channels and
      then focus on presynaptic nicotinic ACh receptors and presynaptic glutamate
      receptors. Finally, we briefly discuss evidence for other types of presynaptic
      ionotropic receptors.

PMID- 10202546
TI  - Molecular biology of odorant receptors in vertebrates.
AB  - The initial step in olfactory discrimination involves the interaction of odorous
      ligands with specific receptors on the surface of olfactory sensory neurons. The
      foundation for a molecular understanding of odor recognition in vertebrates was
      provided by the identification of a family of genes encoding putative odorant
      receptors, by Buck & Axel in 1991. Odorant receptor (OR) genes from the largest
      gene family in the vertebrate genome. This review summarizes progress over the
      past seven years. Major new insights are: Olfaction is accomplished in
      vertebrates by a very large number of receptors; olfactory sensory neurons
      express a small subset of the OR repertoire; in rat and mouse, axons of neurons
      expressing the same OR converge onto defined glomeruli in the olfactory bulb.

PMID- 10202547
TI  - Central nervous system neuronal migration.
AB  - Widespread cell migrations are the hallmark of vertebrate brain development. In
      the early embryo, morphogenetic movements of precursor cells establish the
      rhombomeres of the hindbrain, the external germinal layer of the cerebellum, and
      the regional boundaries of the forebrain. In midgestation, after primary
      neurogenesis in compact ventricular zones has commenced, individual postmitotic
      cells undergo directed migrations along the glial fiber system. Radial migrations
      establish the neuronal layers. Three molecules have been shown to function in
      glial guided migration--astrotactin, glial growth factor, and erbB. In the
      postnatal period, a wave of secondary neurogenesis produces huge numbers of
      interneurons destined for the cerebellar cortex, the hippocampal formation, and
      the olfactory bulb. Molecular analysis of the genes that mark stages of secondary
      neurogenesis show similar expression patterns of a number of genes. Thus these
      three regions may have genetic pathways in common. Finally, we consider emerging
      studies on neurological mutant mice, such as reeler, and human brain
      malformations. Positional cloning and identification of mutated genes has led to
      new insights on laminar patterning in brain.

PMID- 10202548
TI  - Cellular and molecular determinants of sympathetic neuron development.
AB  - The development of the sympathetic nervous system can be divided into three
      overlapping stages. First, the precursors of sympathetic neurons arise from
      undifferentiated neural crest cells that migrate ventrally, aggregate adjacent to
      the dorsal aorta, and ultimately differentiate into catecholaminergic neurons.
      Second, cell number is refined during a period of cell death when neurotrophic
      factors determine the number of neuronal precursors and neurons that survive. The
      final stage of sympathetic development is the establishment and maturation of
      synaptic connections, which for sympathetic neurons can include alterations in
      neurotransmitter phenotype. Considerable progress has been made recently in
      elucidating the cellular and molecular mechanisms that direct each of these
      developmental decisions. We review the current understanding of each of these,
      focusing primarily on events in the peripheral nervous system of rodents.

PMID- 10202549
TI  - Birdsong and human speech: common themes and mechanisms.
AB  - Human speech and birdsong have numerous parallels. Both humans and songbirds
      learn their complex vocalizations early in life, exhibiting a strong dependence
      on hearing the adults they will imitate, as well as themselves as they practice,
      and a waning of this dependence as they mature. Innate predispositions for
      perceiving and learning the correct sounds exist in both groups, although more
      evidence of innate descriptions of species-specific signals exists in songbirds,
      where numerous species of vocal learners have been compared. Humans also share
      with songbirds an early phase of learning that is primarily perceptual, which
      then serves to guide later vocal production. Both humans and songbirds have
      evolved a complex hierarchy of specialized forebrain areas in which motor and
      auditory centers interact closely, and which control the lower vocal motor areas
      also found in nonlearners. In both these vocal learners, however, how auditory
      feedback of self is processed in these brain areas is surprisingly unclear.
      Finally, humans and songbirds have similar critical periods for vocal learning,
      with a much greater ability to learn early in life. In both groups, the capacity
      for late vocal learning may be decreased by the act of learning itself, as well
      as by biological factors such as the hormones of puberty. Although some features
      of birdsong and speech are clearly not analogous, such as the capacity of
      language for meaning, abstraction, and flexible associations, there are striking
      similarities in how sensory experience is internalized and used to shape vocal
      outputs, and how learning is enhanced during a critical period of development.
      Similar neural mechanisms may therefore be involved.

PMID- 10202550
TI  - [Teicoplanin. New treatment potentials for gram-positive infections in the
      hospital].

PMID- 10202551
TI  - [Changes in the properties of the plasma membrane of Acholeplasma laidlawii under
      the action of tetracycline].
AB  - The role of physico-chemical rearrangements in the cell plasmalemma of
      Acholeplasma laidlawii in the development of resistance to tetracycline was
      investigated. The cells of A.laidlawii were shown to be tolerant to tetracycline
      and to preserve a rather high titre of the cells even at a concentration of the
      antibiotic in the inoculation medium much higher than the MIC. The results of the
      investigation of the structural rearrangements in the plasmatic membrane of the
      cells grown in the presence of tetracycline revealed changes in the lipid flow in
      the surface layer and an increase in the cholesterol and phospholipid contents.
      The size of the changes depended on the time of tetracycline addition and the
      phase of the culture growth.

PMID- 10202552
TI  - [The cytotoxicity of mevalonate, lovastatin and carminomycin with respect to MOLT
      4 human malignant T-lymphoblasts in vitro].
AB  - It was shown in vitro that high concentrations of lovastatin, a competitive
      inhibitor of hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibited
      human malignant cells MOLT-4. The activity of lovastatin in doses of 50-250
      microM was dose-dependent. Addition of mevalonate in a concentration of 3 mM to
      the growth medium completely prevented the cytotoxic effect of 100 microM of
      lovastatin. At the same time, exogenous mevalonate did not decrease the
      cytotoxicity of the anthracycline antibiotic carminomycin. Moreover, in a high
      concentration (7 mM) mevalonate slowly but significantly inhibited the growth of
      the malignant target cells and the effect was added to the cytotoxic effect of
      carminomycin low concentrations (0.08 to 0.175 microgram/ml). The results and the
      literature data suggested that combination of mevalonate, HMG-CoA reductase
      inhibitors and anthracyclines could be useful in tumor chemotherapy. The
      suggestion needs further investigation.

PMID- 10202553
TI  - [A new method for the intravital assessment of the functional activity of the
      membrane transporters performing the efflux of antitumor preparations from the
      cells of solid tumor specimens].
AB  - A new method for intravital assessment of the functional activity of anticancer
      drug efflux transporters in intact solid tumor specimens was developed. The
      method is based on the well-known approach to the transporter functional
      evaluation by intracellular accumulation of antitumor drugs and particularly the
      anthracycline antibiotic doxorubicin (Dox). The main new point of the method
      providing investigation of intact solid tumor specimens which markedly simplified
      the procedure is the fact that the intratissue and intracellular accumulation of
      Dox is determined not by the level of the drug in the tissue but by its
      fluorescence decrease in the incubation medium. To assess just the intracellular
      content of Dox and to estimate the transporter functional activity, investigation
      of the influence of membrane transporter inhibitors such as verapamil (P-gp
      inhibitor) and sodium azide (inhibitor of all the energy-dependent ABC
      transporters) on the drug fluorescence decrease in the incubation medium is
      stipulated. The validity of such an approach was experimentally proved with the
      specimens of the Ehrlich solid tumor transplants in mice (a sensitive variant of
      the tumor and the tumor with induced drug resistance). Biopsy specimens of human
      breast tumors were investigated with the new method and functional activity of
      various efflux transporters was revealed: (1) only P-gp, (2) both P-gp and other
      ABC transporters, (3) only transporters different from P-gp, (4) no functional
      activity of efflux transporters. The main trends of the further investigation of
      efflux transporter functional activity in human solid tumors possible for the
      first time with the use of the new method are defined.

PMID- 10202554
TI  - [The determination of individual sensitivity to 5-fluorouracil in patients with
      malignant tumors in different locations].
AB  - Possible determination of individual chemosensitivity of tumors to 5-fluorouracil
      was investigated using new original data and suggestions that lymphocytes of the
      tumor carrier have an ability to assimilate chemical drugs. Such an ability is
      likely due to the fact that 5-fluorouracil as an antimetabolite converted its
      action by inclusion of lymphocytes to the nucleic acid metabolism. The relation
      between the phenomenon and the chemotherapy efficacy is possibly realized through
      two mechanisms. One of them is the direct cytotoxic action of chemical drugs on
      lymphocyte tumor-associated clones resulting in impairment of the tumor growth
      control. The other is possible participation of lymphocytes in transport of
      chemical drugs to the tumor tissue. The in vitro model for estimation of tumor
      carrier chemosensitivity by the level of the nucleic acid metabolism reflects the
      impact of the immune system on realization of the antitumor effect of chemical
      drugs.

PMID- 10202555
TI  - [The immunomodulating action of aminoglycoside antibiotics via different
      administration technics].
AB  - It was shown that intramuscular administration of aminoglycosides such as
      gentamicin and amikacin had an immunosuppressive action in healthy animals.
      Administration of the antibiotics entrapped in erythrocyte shades increased the
      immune response. The immunostimulating effect was higher when the aminoglycosides
      entrapped in allogenic erythrocytes were administered. After the routine
      administration of the antibiotics they were detected in the blood and urine
      within the first hours after the administration. After administration of the
      antibiotics entrapped in erythrocyte shades their detection was later in time.
      When the aminoglycosides entrapped in allogenic erythrocytes were administered
      they were not detected in the biological fluids.

PMID- 10202556
TI  - [Macrolides and phagocytosis].

PMID- 10202557
TI  - [Experience with and the outlook for the use of pectins in therapeutic practice].

PMID- 10202558
TI  - The complexities of CD28 and CTLA-4 signalling: PI3K and beyond.
AB  - A successful immune response requires a set of non-cognate cell-cell interactions
      which provide the second "costimulatory" signal to the T cells. The best
      characterized costimulatory receptor expressed on resting T cells is CD28 which
      provides poorly-defined cyclosporin-resistant biochemical signal(s) that promote
      expression of several cytokines/chemokines. Another major effect of CD28 ligation
      is the promotion of cell survival which is thought to occur via the up-regulation
      of Bcl-xL expression, CD28 shares its ligands B7.1 and B7.2 with the related CTLA
      4, which plays an inhibitory role in T cell activation. Manipulation of CD28/CTLA
      4 interactions with their natural ligands has provided exciting results in
      transplantation and tumor therapy settings and also has potential in the
      treatment of several diseases such as arthritis and multiple sclerosis, asthma
      and protection against HIV infection. The biochemical basis for the different
      functional outcomes of CD28 and CTLA-4 ligation has been the subject of intense
      investigation over the past few years. This review will focus on our current
      understanding of the biochemical signals that may be involved in regulating the
      different functional outcomes of CD28 and CTLA-4, with particular emphasis on the
      role played by the PI3K-dependent signalling cascade.

PMID- 10202559
TI  - Thymic peptides and preparations: an update.
AB  - The possibilities of thymic peptides in human therapy are still being described.
      Here, we focus on their general characteristics and on recent advances in this
      area.

PMID- 10202560
TI  - Tumor escape from immune surveillance.
AB  - The bases for an efficient anti-tumor immune response begin to be better defined.
      Nonetheless, neoplastic cells develop various strategies to escape immune
      surveillance, which are discussed here in order to better design the therapeutic
      possibilities of immune manipulation. The absence of specific tumor antigen as
      well as the weak expression of major histocompatibility complex (MHC) molecules
      hinder the recognition of the neoplastic cells by T lymphocytes. The defect of
      expression by the tumor of the ligands for the T cell activation costimulatory
      molecules is particularly harmful for the immune response since it induces
      tolerance. Finally, tumor cells can inactivate effector T lymphocytes through the
      secretion of inhibitory cytokines, induction of apoptosis or functional
      inactivation. The multiplicity of the means to oppose an effective anti-tumor
      response challenges the adaptative mechanisms of the immune system. For example,
      the natural killer cells target tumor cells not expressing MHC class I molecules.
      Numerous possibilities of tumor immunogenicity restoration have been demonstrated
      at least in vitro, such as stimulation of the cancerous cells by CD40 or cytokine
      treatment, which could lead to several promising therapeutical approaches.

PMID- 10202561
TI  - Human acid-labile interferon alpha.
AB  - In acquired immune deficiency syndrome (AIDS) and autoimmune diseases, like
      systemic lupus erythematosus (SLE), persisting high levels of interferon (IFN)
      are detectable in plasma. The IFN has been identified as an unusual human acid
      labile IFN-alpha (al-IFN-alpha). Its properties are similar to that of the known
      alpha interferons except sensitivity to acid treatment (pH 2) which is
      characteristic for IFN-gamma. The nature of al-IFN-alpha is not known. Four
      hypotheses have been presented that suggested that: a) al-IFN-alpha may be a
      product of a distinct IFN gene; b) or a posttranscriptionally modified IFN-alpha
      molecule; c) the phenomenon of al-IFN-alpha may be an effect of synergistic
      action of a mixture of acid-stable IFN-alpha and acid-labile IFN-gamma; d) or the
      effect may be a result of an interaction of acid-stable IFN-alpha with an unknown
      factor(s) present in plasma and associated with progression of HIV infection or
      autoimmune diseases. Neither of the hypotheses have been experimentally proven.
      To verify the most probable hypothesis of the synergistic interactions between
      the acid stable and labile IFNs, the experiments with the artificial mixtures of
      nHuIFN-alpha and rHuIFN-gamma were performed. The synergistic effect was
      abolished by the treatment either with pH 2 or with anti-IFN-gamma antibodies.
      The residual activity was similar in both cases and corresponded to acid-stable
      IFN-alpha. However, al-IFN-gamma (AIDS serum with high IFN level) was found to be
      much more sensitive to acid treatment and only negligible effect of anti-IFN
      gamma serum was observed. It suggests that the synergistic effect may be only
      slightly responsible for the phenomenon of acid lability of IFN-alpha. For
      explanation of the occurrence of al-IFN-alpha the hypothesis of existence of a
      factor(s) interacting with IFN-alpha should be taken into consideration.

PMID- 10202562
TI  - Substance abuse and HIV-gp120: are opiates protective?
AB  - There has long been a popular conceptual linkage between human immunodeficiency
      virus (HIV) acquisition and substance abuse involving "needles". Indeed, in vitro
      studies demonstrate that these substances promote the replication of HIV.
      Included in these in vitro studies is a linkage or association of tissue damage
      and viral load with the actions HIV envelope protein gp120 with substances of
      abuse. However, detailed epidemiological studies have not supported this
      association of substance abuse and HIV acquisition, viral load and exacerbated
      tissue damage. It is with this understanding that we undertake a reevaluation of
      the in vitro studies within the context of the microvascular immune environment.
      In this regard, a counter-intuitive hypothesis emerges, namely, that specific
      substances of abuse may afford a degree of protection from HIV infection. This
      new hypothesis involves the neural, immune, and vascular signaling molecule
      nitric oxide.

PMID- 10202563
TI  - Interferon gamma as immunomodulator in a patient with multiple myeloma.
AB  - We describe here a patient with multiple myeloma, who, while in remission after
      chemotherapy, received 100 micrograms of rIFN-gamma (Imukin, Boehringer,
      Ingelheim) subcutaneously 3 times a week for 4 weeks as supportive therapy before
      autologous peripheral blood stem cell transplantation (PBSCT). The patient was
      monitored for serum IFN, TNF, IL-2 activities and for the ability of peripheral
      blood leukocytes (PBL) to produce IFN-alpha/beta, IFN-gamma, IL-2 and TNF-alpha
      after in vitro induction. Changes in the percent of plasma cells in the bone
      marrow, in the total and differential white blood cell counts, in T cell subsets
      and NK cells were also monitored. IFN-gamma yielded no clinical antitumor
      activity. The number of bone marrow plasma cells increased, however, the
      percentage of blood and bone marrow NK cells and the CD4/CD8 T cell subset ratio
      decreased. Monitoring the cytokine production ability of PBL during IFN-gamma
      therapy revealed an increase in IL-2, IFN-gamma and TNF-alpha titers produced
      upon in vitro induction after 2 weeks of treatment (6 injections of rIFN-gamma).
      However, after 9 injections there was a significant decrease in IFN-gamma and IL
      2 production in the PBL, and at the end of therapy (12 injections) the decrease
      not only in IL-2 and in IFN-gamma but also in IFN-alpha production was observed.
      In contrast to these changes, TNF production was strongly enhanced and reached
      the level observed before the therapy. These data suggest that the schedule of
      IFN-gamma therapy in multiple myeloma should perhaps be adapted to become more
      effective, taking advantage from the immunomodulating activity of IFN-gamma.

PMID- 10202564
TI  - Lactoferrin increases the output of neutrophil precursors and attenuates the
      spontaneous production of TNF-alpha and IL-6 by peripheral blood cells.
AB  - The aim of this report was to investigate the effects of bovine lactoferrin (BLF)
      taken orally (per os) by healthy individuals, on selected immune parameters.
      Three groups of volunteers (7 persons per group) were taken daily for 7 days, one
      capsule containing 2, 10 or 50 mg of BLF. A control group has taken placebo only.
      Venous blood was taken for tests a few hours before the first dose of BLF, one
      day and 14 days after the last dose of the preparation. For the evaluation of BLF
      action on the immune response system we have chosen 3 parameters: content of
      neutrophil precursors in the peripheral blood (in percentage), spontaneous
      production of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) by
      unstimulated blood cell cultures. We found that oral treatment of volunteers with
      BLF caused a transient (one day after last dose) increase of immature forms of
      neutrophils in the circulating blood. That increase was more than 2-fold in the
      case of 10 mg dose. However, statistically significant increases in the
      percentage of neutrophil precursors were also registered at doses of 2 and 50 mg
      of BLF. No change in the immature cell content was observed in the placebo group.
      The treatment with BLF also resulted in a profound decrease of the spontaneous
      production of IL-6 and TNF-alpha by cultures of peripheral blood cells. This
      decrease was significant (10 mg/dose) one day following the last dose of BLF and
      persisted for additional 14 days. These results confirmed our earlier data on the
      effects of per os treatment with a nutritional preparation containing BLF.
      Furthermore, we were able to closer establish the optimal dose of BLF affecting
      selected immune indices.

PMID- 10202565
TI  - Hydrogen peroxide in expired air condensate correlates positively with early
      steps of peripheral neutrophil activation in asthmatic patients.
AB  - We have found an increased H2O2 level in expired air of asthmatic patients.
      Neutrophils from these subjects generated higher amounts of superoxide radicals
      after challenge with phorbol esters than those from healthy subjects which may
      result from an increased activity of NADPH-oxidase. The enhanced Ca2+
      mobilisation in neutrophils from asthmatics could be responsible for increased
      production and subsequent elevated H2O2 concentration in expired breath
      condensate. In this study we wished to determine whether neutrophils of asthmatic
      patients have enhanced [Ca2+]i response after N-formyl-methionyl-leucyl
      phenylalanine--fMLP challenge as compared with cells from healthy donors, and if
      so, does it correlate with H2O2 levels in expired air. We examined 21 patients,
      10 healthy individuals as a control group (mean age 34.3 +/- 5.5, 6 males and 4
      females) and 11 asthmatic subjects (mean age 38.2 +/- 7.2, 7 males and 4
      females). The rise of [Ca2+]i as an early event of neutrophil activation, was
      measured spectrofluorimetically with Fura-2-AM. The mean H2O2 level, measured
      spectrofluorimetrically in the expired breath of asthmatics, was 20-fold higher
      than that in healthy control (0.18 +/- 0.20 vs. 0.01 +/- 0.04 microM, p < 0.05).
      [Ca2+]i increase after challenge by fMLP (delta [Ca2+]i) was much higher in
      asthmatics than in control group (205.0 +/- 44 vs. 113.0 +/- 22 nM, p < 0.05,
      respectively). A strong correlation was observed between H2O2 and delta [Ca2+]i
      and maximal velocity of increase in [Ca2+]i in asthmatics (r = 0.87, p < 0.01 and
      r = 0.64, p < 0.05). We conclude that elevated H2O2 level in the expired breath
      condensate of asthmatics can be generated by activated neutrophils in the course
      of mucosal inflammation observed in bronchial asthma.

PMID- 10202566
TI  - Does stress damage the brain?
AB  - Studies in animals showed that stress results in damage to the hippocampus, a
      brain area involved in learning and memory, with associated memory deficits. The
      mechanism involves glucocorticoids and possibly serotonin acting through
      excitatory amino acids to mediate hippocampal atrophy. Patients with
      posttraumatic stress disorder (PTSD) from Vietnam combat and childhood abuse had
      deficits on neuropsychological measures that have been validated as probes of
      hippocampal function. In addition, magnetic resonance imaging (MRI) showed
      reduction in volume of the hippocampus in both combat veterans and victims of
      childhood abuse. In combat veterans, hippocampal volume reduction was correlated
      with deficits in verbal memory on neuropsychological testing. These studies
      introduce the possibility that experiences in the form of traumatic stressors can
      have long-term effects on the structure and function of the brain.

PMID- 10202568
TI  - Brain activation in PTSD in response to trauma-related stimuli.
AB  - BACKGROUND: Repetitive recall of traumatic memories and chronic intermittent
      hyperarousal are characteristic of posttraumatic stress disorder (PTSD).
      Hyperarousal and memory dysfunction implicates "limbic" brain regions, including
      the amygdaloid complex, hippocampal formation, and limbic cortex, such as the
      orbitofrontal and anterior cingulate areas. To investigate the neurobiologic role
      of these brain regions in PTSD, we measured regional cerebral blood flow in PTSD
      with single photon emission computerized tomography (SPECT) during a symptom
      provocation paradigm. METHODS: Fourteen Vietnam veterans with PTSD, 11 combat
      control subjects, and 14 normal control subjects were studied with [99mTc]HMPAO
      in two sessions 48 hours apart: one session after exposure to white noise and the
      other following exposure to combat sounds. Skin conductance, heart rate, and
      subjective experience were recorded at the time of the studies. RESULTS:
      Activation for all three groups occurred in the anterior cingulate/middle
      prefrontal gyrus. Activation in the region of the left amygdala/nucleus accumbens
      was found in PTSD patients only. Deactivation was found in all three groups in
      the left retrosplenial region. CONCLUSIONS: These findings implicate regions of
      the "limbic" brain, which may mediate the response to aversive stimuli in healthy
      individuals and in patients suffering from PTSD.

PMID- 10202567
TI  - Neural correlates of exposure to traumatic pictures and sound in Vietnam combat
      veterans with and without posttraumatic stress disorder: a positron emission
      tomography study.
AB  - BACKGROUND: Patients with posttraumatic stress disorder (PTSD) show a reliable
      increase in PTSD symptoms and physiological reactivity following exposure to
      traumatic pictures and sounds. In this study neural correlates of exposure to
      traumatic pictures and sounds were measured in PTSD. METHODS: Positron emission
      tomography and H2[15O] were used to measure cerebral blood flow during exposure
      to combat-related and neutral pictures and sounds in Vietnam combat veterans with
      and without PTSD. RESULTS: Exposure to traumatic material in PTSD (but not non
      PTSD) subjects resulted in a decrease in blood flow in medial prefrontal cortex
      (area 25), an area postulated to play a role in emotion through inhibition of
      amygdala responsiveness. Non-PTSD subjects activated anterior cingulate (area 24)
      to a greater degree than PTSD patients. There were also differences in cerebral
      blood flow response in areas involved in memory and visuospatial processing (and
      by extension response to threat), including posterior cingulate (area 23),
      precentral (motor) and inferior parietal cortex, and lingual gyrus. There was a
      pattern of increases in PTSD and decreases in non-PTSD subjects in these areas.
      CONCLUSIONS: The findings suggest that functional alternations in specific
      cortical and subcortical brain areas involved in memory, visuospatial processing,
      and emotion underlie the symptoms of patients with PTSD.

PMID- 10202569
TI  - Abnormal mismatch negativity in women with sexual assault-related posttraumatic
      stress disorder.
AB  - BACKGROUND: Disturbances in sensory processing have been hypothesized in
      individuals with posttraumatic stress disorder (PTSD). The authors investigated
      this possibility by using mismatch negativity (MMN), an event-related potential
      (ERP) that reflects the operation of a preconscious cortical detector of stimulus
      change. METHODS: Thirteen medication-free women with sexual assault-related PTSD
      were compared with 16 age-matched, healthy comparison women without PTSD. ERPs
      were elicited by regularly presented "standard" auditory stimuli and by
      infrequently occurring "deviant" auditory stimuli, which differed slightly in
      frequency. The MMN was identified in the subtraction waveforms as the difference
      between ERPs elicited by the deviant and standard stimuli. Group comparisons of
      P50, N1, P2, and N2 to the standard and to the deviant stimuli, and of the MMN in
      the subtraction waveform were performed. RESULTS: The amplitude of the MMN was
      significantly greater in the PTSD compared to the non-PTSD women. MMN was
      significantly correlated with the total Mississippi PTSD Symptom Scale score in
      the PTSD group. No significant group differences were noted in P50, N1, or P2
      responding. Significant group differences in N2 were due to the increased MMN in
      PTSD subjects. CONCLUSIONS: The data provide evidence for abnormalities in
      preconscious auditory sensory memory in PTSD, whereas earlier studies have
      reported abnormalities in conscious processing. These data suggest an increased
      sensitivity to stimulus changes in PTSD and implicate the auditory cortex in the
      pathophysiology of the disorder.

PMID- 10202570
TI  - Elevated serum interleukin-6 (IL-6) and IL-6 receptor concentrations in
      posttraumatic stress disorder following accidental man-made traumatic events.
AB  - BACKGROUND: Recently, it has been reported that serum interleukin-1 beta (IL-1
      beta), but not soluble IL-2 receptor (sIL-2R), concentrations were significantly
      higher in patients with posttraumatic stress disorder (PTSD) than in normal
      volunteers, and that psychological stress in humans is associated with increased
      secretion of proinflammatory cytokines, such as IL-6. METHODS: The aim of the
      present study was to examine the inflammatory response system in patients with
      PTSD through measurements of serum IL-6, sIL-6R, sgp130 (the IL-6 signal
      transducing protein), sIL-1R antagonist (sIL-1RA; an endogenous IL-1 receptor
      antagonist), CC16 (an endogenous anticytokine), and sCD8 (the T suppressor
      cytotoxic antigen). RESULTS: Serum IL-6 and sIL-6R, but not sgp130, sIL-RA, CC16,
      or sCD8, concentrations were significantly higher in PTSD patients than in normal
      volunteers. Serum sIL-6R concentrations were significantly higher in PTSD
      patients with concurrent major depression than in PTSD patients without major
      depression and normal volunteers. There were no significant relationships between
      serum IL-6 or sIL-6R and severity measures of PTSD. CONCLUSIONS: The results
      suggest that PTSD is associated with increased IL-6 signaling. It is hypothesized
      that stress-induced secretion of proinflammatory cytokines is involved in the
      catecholaminergic modulation of anxiety reactions.

PMID- 10202571
TI  - Low platelet-poor plasma concentrations of serotonin in patients with combat
      related posttraumatic stress disorder.
AB  - BACKGROUND: Combat-related posttraumatic stress disorder (CR-PTSD) is associated
      with a dysregulation of various neurotransmitter systems. METHODS: We assessed
      levels of platelet-poor plasma (PPP) norepinephrine (NE), and serotonin (5-HT),
      and 24-hour urinary excretion of NE, dopamine (DA), and homovanillic acid (HVA)
      in 17 male outpatients with untreated chronic CR-PTSD (age, 33.1 +/- 7.4 years)
      and 10 normal control subjects (age, 35.8 +/- 2.7 years). RESULTS: Compared with
      the control subjects, the PTSD patients showed significantly lower PPP 5-HT
      levels, elevated PPP NE levels, and significantly higher mean 24-hour urinary
      excretion of all three catecholamines (NE, DA, and HVA). The 24-hour urinary HVA
      values of the CR-PTSD patients correlated significantly and positively with the
      total Impact of Event Scale scores and the avoidance symptoms cluster scores, and
      the PPP 5-HT levels correlated negatively with the Hamilton Anxiety Rating Scale
      scores. The PPP NE/5-HT ratio was significantly higher in the study group than in
      the control subjects. CONCLUSIONS: We believe this combined enhanced
      noradrenergic activity and diminished 5-HT activity may be relevant to the
      neurobiology of CR-PTSD.

PMID- 10202572
TI  - Psychotic features and illness severity in combat veterans with chronic
      posttraumatic stress disorder.
AB  - BACKGROUND: Psychotic symptoms may be present in up to 40% of patients with
      combat-related posttraumatic stress disorder (PTSD). In this study, we
      hypothesized that severity of psychotic symptoms would also reflect severity of
      PTSD symptoms in patients with well-defined psychotic features. METHODS: Forty
      five Vietnam combat veterans with PTSD but without a primary psychotic disorder
      diagnosis underwent a Structured Clinical Interview for DSM-III-R with Psychotic
      Screen, and the Clinician Administered PTSD Scale (CAPS). Patients identified as
      having psychotic features (PTSD-P), (n = 22) also received the Positive and
      Negative Syndrome Scale (PANSS) and the Hamilton Depression Rating Scale (HDRS).
      RESULTS: There was a significant positive correlation between the CAPS and PANSS
      global ratings (p < .001) and the HDRS and PANSS (p < .03) in the PTSD-P
      patients. Many CAPS and PANSS subscales also demonstrated significant
      intercorrelations; however, the CAPS-B subscale (reexperiencing) and the PANSS
      positive symptom scale were not correlated, suggesting that psychotic features
      may not necessarily be influenced or accounted for by more severe reexperiencing
      symptoms. Fifteen (68%) of the PTSD-P patients had major depression (MDD). Both
      CAPS and PANSS ratings were significantly higher in the PTSD-P patients with
      comorbid MDD. CONCLUSIONS: As postulated, patients with more severe psychosis
      ratings are likely to have more severe PTSD disease burden if psychotic features
      are present. This study further documents the occurrence of psychotic features in
      PTSD that are not necessarily due to a primary psychotic disorder, suggesting
      that this may be a distinct subtype; however, a significant interaction likely
      exists between PTSD, depression, and psychotic features.

PMID- 10202573
TI  - Heightened transcription for enzymes involved in norepinephrine biosynthesis in
      the rat locus coeruleus by immobilization stress.
AB  - BACKGROUND: The locus coeruleus (LC), a target for CRH neurons, is critically
      involved in responses to stress. Various physiological stresses increase
      norepinephrine turnover, tyrosine hydroxylase (TH) enzymatic activity, protein
      and mRNA levels in LC cell bodies and terminals; however, the effect of stress on
      other enzymes involved in norepinephrine biosynthesis in the LC is unknown.
      METHODS: Rats were exposed to single (2 hour) or repeated (2 hour daily)
      immobilization stress (IMO). Recombinant rat dopamine b-hydroxylase (DBH) cDNA
      was expressed in E. coli and used to generate antisera for immunohistochemistry
      and immunoblots in LC. Northern blots were used to assess changes in mRNA levels
      for TH, DBH, and GTP cyclohydrolase I (GTPCH) in the LC in response to the
      stress. Conditions were found to isolate nuclei from LC and to use them for run
      on assays of transcription. RESULTS: Repeated stress elevated the DBH
      immunoreactive protein levels in LC. Parallel increases in TH, DBH and GTPCH mRNA
      levels of about 300% to 400% over control levels were observed with single IMO,
      and remained at similar levels after repeated IMO. This effect was
      transcriptionally mediated, and even 30 min of a single IMO significantly
      increased the relative rate of transcription. CONCLUSIONS: This study is the
      first to reveal transcriptional activation of the genes encoding catecholamine
      biosynthetic enzymes in the LC by stress. In addition to TH, changes in DBH and
      GTPCH gene expression may also contribute to the development of stress-triggered
      affective disorders.

PMID- 10202574
TI  - Subcortical correlates of differential classical conditioning of aversive
      emotional reactions in social phobia.
AB  - BACKGROUND: Conditioning processes have been proposed to play a role in the
      development of anxiety disorders. As yet, the neurobiologic correlates of
      emotional learning have not been fully understood in these patients. Accordingly,
      brain activity was studied in subcortical and cortical regions involved in the
      processing of negative affect during differential aversive classical
      conditioning. METHODS: Twelve patients with social phobia and 12 healthy control
      subjects were presented with paired conditioned (CS; neutral facial expressions)
      and unconditioned stimuli (US; negative odor vs unmanipulated air). Functional
      magnetic resonance imaging (fMRI) was utilized to examine regional cerebral
      activity during habituation, acquisition,a nd extinction trials. Activity was
      measured with echo-planar-imaging (EPI), and signal intensity in individually
      defined anatomic regions were analyzed. RESULTS: Subjective ratings of emotional
      valence to the CS indicated that behavioral conditioning occurred in both groups.
      The presentation of CS associated with negative odor led to signal decreases in
      the amygdala and hippocampus of normal subjects, whereas an opposite increased
      activation in both regions was observed in patients. Regional differences were
      not found during habituation and extinction. CONCLUSIONS: Results suggest that
      conditioned aversive stimuli are processed in subcortical regions, with phobic
      patients differing from control subjects.

PMID- 10202575
TI  - Neuroanatomic correlates of CCK-4-induced panic attacks in healthy humans: a
      comparison of two time points.
AB  - BACKGROUND: Several functional imaging studies have demonstrated increases of
      brain activity in the temporofrontal, cingulate, and claustrum regions during a
      pharmacologically induced panic attack when scanning was done at a single point
      in time. However, no study has evaluated changes in brain activity at two time
      points during a panic attack. We hypothesized that in response to a single bolus
      injection of the panicogen cholecystokinin-4 (CCK-4) in healthy volunteers,
      changes in regional cerebral blood flow (rCBF) might be different if scanning
      were done at two different time points. METHODS: To test this hypothesis, we
      conducted a single-blind study, using positron emission tomography (PET). To
      determine the time effect of panic attack on brain activity, we performed either
      early scan or late scan covering the first or the second minute after CCK-4 bolus
      injection, respectively. The PET images were analyzed by statistical parametric
      mapping (SPM) followed by region of interest (ROI) analysis. RESULTS: The results
      showed significant differences between the early and the late scan. The early
      effects of CCK-4 are accompanied by increases in rCBF in the hypothalamic region,
      whereas the late scan showed an increase in rCBF in the claustrum-insular region.
      Reductions in rCBF were observed for both time groups in the medial frontal
      region. A separate scan for anticipatory anxiety demonstrated rCBF increases in
      the anterior cingulate region and decreases in the occipital regions.
      CONCLUSIONS: These results may support the hypothesis that changes in rCBF as a
      function of time during CCK-4-induced panic might correspond to a neurocircuitry
      involved in panic attacks.

PMID- 10202577
TI  - Functional magnetic resonance imaging study of frontal lobe activation during
      word generation in obsessive-compulsive disorder.
AB  - BACKGROUND: Functional imaging studies have demonstrated abnormal patterns of
      brain activity in obsessive-compulsive disorder, which consistently suggest the
      alteration of frontal lobe functioning. We performed a brain activation study in
      obsessive-compulsive disorder using a cognitive task involving the frontal lobes.
      METHODS: Twenty patients and 20 healthy control subjects were assessed with
      functional magnetic resonance imaging during a phonologically guided word
      generation task. The study analysis was based on the comparison of group average
      time-course functional changes occurring at the site of largest frontal cortex
      activation during alternating rest and task periods. RESULTS: In terms of
      relative signal changes, patients showed a significantly greater activation
      during word generation and a defective suppression of this activation during the
      following rest period. Both abnormal imaging findings significantly correlated
      with the severity of the clinical process assessed by the Yale-Brown Obsessive
      Compulsive Scale. CONCLUSIONS: The results indicate that functional magnetic
      resonance imaging during cognitive challenge may be useful to reveal distinctive
      features of latent brain dysfunction in obsessive-compulsive disorder.

PMID- 10202576
TI  - P50 suppression and prepulse inhibition of the startle reflex in humans: a
      correlational study.
AB  - BACKGROUND: Sensory gating is an important feature of the normally functioning
      brain. When not operating correctly, it can contribute to different kinds of
      psychiatric illnesses by flooding the higher brain functions with useless
      information. Over the years, two paradigms have evolved to quantify the amount of
      sensory gating: the prepulse inhibition (PPI) of the startle reflex and the
      suppression of the P50 evoked potential. To enable comparison across studies it
      is important to find out to what extent these paradigms reflect the same
      processes. In the present study, this relationship was explored. METHODS: Thirty
      one healthy male volunteers with no personal or family history of mental illness
      were tested on their ability to suppress the P50 wave and to inhibit the startle
      reflex. RESULTS: A significant positive correlation was found between PPI and P50
      suppression mainly early in testing, when habituation of the startle reflex is
      taking place. Furthermore, a significant negative correlation was found between
      P50 suppression in the second half of testing and the habituation of the startle
      reflex. CONCLUSIONS: PPI and P50 suppression are correlated at an early stage of
      testing, when the process of habituation of the startle reflex is active. The
      role of the habituation in the correlation between these two measures needs to be
      further explored.

PMID- 10202578
TI  - Neuropsychological functioning in a subclinical obsessive-compulsive sample.
AB  - BACKGROUND: Previous neuropsychological research has suggested that the study of
      psychometrically defined subclinical samples might be a valid approach to
      understand the underlying pathophysiology of obsessive-compulsive disorder (OCD).
      This approach has the potential benefit of overcoming some of the methodological
      problems linked to the use of clinical samples. METHODS: A group of subclinical
      obsessive-compulsive (OC) subjects (n = 35), selected on the basis of their
      scores on the Padua Inventory, and a control group were assessed on executive
      functioning tasks and other neuropsychological tests which have been demonstrated
      to be impaired in clinical OCD patients and/or in those with several basal
      ganglia disorders. RESULTS: Subclinical OC subjects needed significantly more
      moves than controls to reach the solution criteria on the Tower of Hanoi puzzle,
      and performance on this test was positively correlated with total score and the
      Checking factor of the Padua Inventory. There were no between-group differences
      on the other frontal lobe tests. CONCLUSIONS: The results suggest that deficits
      in manipulating spatial information might be basic in OCD, and are congruent with
      the involvement of the frontostriatal circuits in the disorder.

PMID- 10202579
TI  - Organizational strategies mediate nonverbal memory impairment in obsessive
      compulsive disorder.
AB  - BACKGROUND: Previous neuropsychological studies of obsessive-compulsive disorder
      (OCD) have indicated impaired executive functioning and nonverbal memory. The
      extent to which impaired executive functioning impacts nonverbal memory has not
      been established. The current study investigated the mediating effects of
      organizational strategies used when copying a figure on subsequent nonverbal
      memory for that figure. METHODS: We examined neuropsychological performance in 20
      unmedicated subjects with OCD and 20 matched normal control subjects. Subjects
      were administered the Rey-Osterrieth Complex Figure Test (RCFT) and
      neuropsychological tests assessing various aspects of executive function.
      RESULTS: OCD subjects differed significantly from healthy control subjects in the
      organizational strategies used to copy the RCFT figure, and they recalled
      significantly less information on both immediate and delayed testing. Multiple
      regression analyses indicated that group differences in immediate percent recall
      were significantly mediated by copy organizational strategies. Further
      exploratory analyses indicated that organizational problems in OCD may be related
      to difficulties shifting mental and/or spatial set. CONCLUSIONS: Immediate
      nonverbal memory problems in OCD subjects were mediated by impaired
      organizational strategies used during the initial copy of the RCFT figure. Thus,
      the primary deficit was one affecting executive function, which then had a
      secondary effect on immediate memory. These findings are consistent with current
      theories proposing frontal-striatal system dysfunction in OCD.

PMID- 10202580
TI  - Midlatency evoked potentials attenuation and augmentation reflect different
      aspects of sensory gating.
AB  - A broad definition of sensory gating refers to the ability of the brain to
      modulate its sensitivity to incoming sensory stimuli. This definition allows the
      concept of gating to include both the capacities to minimize or stop responding
      to incoming irrelevant stimuli (gating out) and to respond when a novel stimulus
      is presented or a change occurs in ongoing stimuli (gating in). In order to
      further characterize the function of sensory gating, we examined the attenuation
      (decreased responding) and augmentation (increased responding) of the P50 EP
      amplitudes in 22 normal volunteers. Three EP paradigms, each including a number
      of conditions, designed to examine both EP habituation (inhibition) and
      dishabituation (excitation) were administered to each subject. In conditions
      designed to examine habituation (identical pairs of clicks or trains of
      repetitive identical clicks), the P50 behaved, as expected, with decrease of the
      amplitude with repetition. In conditions designed to examine dishabituation the
      amplitude of the P50, EP did not decrease as much (and frequently increased) with
      stimulus change. The results suggest that the P50 EP is sensitive to the effects
      of stimulus repetition and stimulus change and can be used to study the different
      aspects of sensory gating.

PMID- 10202581
TI  - The 35% CO2 inhalation procedure: test-retest reliability.
AB  - The subjective response to a single-breath, 35% carbon dioxide challenge test
      shows promise as a tool for the study of panic disorder and may comprise a trait
      marker for that disorder. Little has been done to measure the reliability of test
      results, however. Subjects took a single breath at 35% CO2 and completed a self
      rating of anxiety symptoms immediately thereafter. This procedure was repeated
      after a mean interval of 29 days. One group, considered at high risk for panic
      disorder, consisted of well, first-degree relatives of individuals treated for
      panic disorder. The control group included well subjects at high risk for
      affective disorder and subjects who had family histories negative for both
      affective disorder and panic disorder. On both testing occasions, subjects at
      high risk for panic disorder had symptom scores that were significantly higher
      than those of control subjects. Group differences in the portions who experienced
      a panic attack were dependent on the symptom threshold used to define an attack.
      A lower threshold was optimal with the second testing and a single, positive test
      result appeared to be more meaningful than a single negative result. The majority
      of individual symptom ratings were highly correlated across tests. Ratings for
      "smothering sensations," in particular, correlated highly across tests and
      consistently discriminated high-risk from control subjects. The sources of test
      result variability are unclear and warrant more investigation before the tests
      can be clinically useful. Research efforts should seek optimal thresholds to
      define positive test results within given data sets.

PMID- 10202583
TI  - Normal CSF oxytocin and NPY levels in OCD.
AB  - BACKGROUND: Attention has recently been focused on central nervous system
      neuropeptides as potential mediators of the symptom profile of obsessive
      compulsive disorder (OCD). Increased CSF levels of the anxiolytic neuropeptide
      oxytocin have been reported in OCD. CSF levels of NPY, another anxiolytic
      neuropeptide, have not been studied. METHODS: We measured CSF oxytocin and NPY in
      14 OCD patients and 26 healthy normal volunteers. RESULTS: There were no
      significant differences between the OCD patients and control subjects in CSF
      oxytocin or NPY levels. In both the OCD and control groups, women had
      significantly higher CSF oxytocin levels than men. CONCLUSIONS: These results do
      not support a prior finding of elevated CSF oxytocin in OCD patients and do not
      provide any evidence for an abnormality of NPY regulation in OCD.

PMID- 10202582
TI  - D-fenfluramine challenge in posttraumatic stress disorder.
AB  - BACKGROUND: Much progress has been made in understanding the role of
      catecholamines in the pathophysiology of posttraumatic stress disorder (PTSD).
      Recent research has broadened the scope of neuroregulation of PTSD to include
      serotonin. METHODS: We used the serotonin-releasing agent and reuptake inhibitor,
      d-fenfluramine, to assess the integrity of the serotonin-mediated prolactin
      release in 8 men with combat-induced PTSD and 8 healthy men. RESULTS: The
      veterans with PTSD had a significantly lower prolactin response to d-fenfluramine
      as compared to healthy control subjects. The prolactin response to d-fenfluramine
      was inversely correlated with the patient's level of PTSD symptomatology and
      measures of aggression. CONCLUSIONS: This study demonstrates a central serotonin
      dysfunction, as reflected in a lower prolactin response to d-fenfluramine, in
      patients with PTSD.

PMID- 10202584
TI  - Serotonin 1A receptor messenger RNA regulation in the hippocampus after acute
      stress.
AB  - BACKGROUND: When rats are subjected to chronic stress for 2 weeks, a significant
      decrease in hippocampal serotonin (5-HT)1A messenger RNA (mRNA) is observed. We
      wanted to investigate whether stress, administered for shorter periods of time,
      would result in decreases in 5-HT1A gene expression in hippocampus. METHODS: In
      one experiment, rats were either stressed daily for 1 week or implanted with two
      corticosterone pellets to produce elevated corticosterone levels. In another
      experiment, rats were subjected to a severe acute stressor and sacrificed 1 day
      or 1 week after the stressor. RESULTS: We found that 24 hours after the acute
      stress, rats showed a significant decrease in 5-HT1A mRNA levels in CA1 and the
      dentate gyrus compared to controls. No significant changes in 5-HT1A mRNA levels
      were detected in any of the other groups. CONCLUSIONS: Although 1 week of chronic
      stress is not sufficient to cause significant decreases in hippocampal 5-HT1A
      mRNA levels, a severe and prolonged acute stress is capable of down-regulating,
      at least transiently, 5-HT1A mRNA gene expression in hippocampus.

PMID- 10202585
TI  - Rapid eye movement sleep changes during the adaptation night in combat veterans
      with posttraumatic stress disorder.
AB  - BACKGROUND: Hyperarousal in posttraumatic stress disorder (PTSD) is manifested
      during sleep as well as waking. Elevated rapid eye movement sleep (REMS) phasic
      activity, likely signifying central nervous system alerting, has been identified
      in PTSD. The authors reasoned that PTSD compared to control subjects would show
      particularly increased REMS phasic activity on the first night of
      polysomnography, with adaptation to a novel environment. METHODS: First-night
      polysomnograms of 17 veterans with PTSD were compared with those of 11 control
      subjects. Sleep was also studied in subsets of both groups over two nights.
      RESULTS: On the first night, the PTSD subjects had a higher density of rapid eye
      movements in the first REMS period. This measure was increased on the first
      compared to the second night, but there was no interaction effect between night
      and group. CONCLUSIONS: REMS changes are again demonstrated in veterans with
      PTSD. Introduction to a novel environment activated a REMS phasic process, but
      not differentially in PTSD compared to control subjects.

PMID- 10202586
TI  - Addressing mental health needs of infants and young children.
AB  - Work with infants and young children is a subspecialty of child psychiatry.
      Special areas of expertise and clinical skills are required for work in this area
      and even traditional areas of clinical skills--evaluating mental and
      developmental competency, collaborations with other professionals, synthesizing
      information for parents--have an added valence when applied to work with very
      young children. Furthermore, in the last three decades, there has been a
      remarkable increase in knowledge about the first years of life. Most recently,
      understanding about early brain development and the complex interactions among
      biology, environment, and experience in shaping early development has highlighted
      the critical nature of psychological interventions in the first years of life.
      Providing mental health services for very young children requires a
      multidisciplinary approach, and the field has evolved simultaneously in the
      disciplines of child psychiatry, pediatrics, psychology, social work, neurology,
      early childhood education, and nursing. With that range of theoretic and
      professional background, the resulting evaluative approaches and services are
      also quite diverse. The agenda for the next decade of work is to bring together
      these multiple viewpoints around critical areas for the development of the field,
      including improved diagnostic nosology, a better understanding of the number of
      young children needing services, pathways for accessing those services, and more
      explicit descriptions of the important features of a mental health intervention
      for very young children and their families.

PMID- 10202587
TI  - Developmental assessment. Its role in comprehensive psychiatric assessment of
      young children.
AB  - The psychiatric assessment of young children is a multifaceted endeavor, and
      developmental assessment, formal or informal, is an integral component. Sound
      developmental assessment, however, is a thoughtful process that requires
      specialized knowledge of young children, appropriate assessment methods, and the
      interpretation and integration of psychiatric and developmental data. The art and
      science of developmental assessment have improved significantly over the past
      century. Despite technologic advances in instruments, clinicians must be as
      astute and mindful as ever of what constitutes sound diagnostic formulation and
      treatment planning. Although many limitations and potential abuses certainly
      exist, results of developmental evaluations play a unique and often essential
      role in the comprehensive psychiatric assessment of young children.

PMID- 10202588
TI  - Diagnostic play interview. Its role in comprehensive psychiatric evaluation.
AB  - The purpose of this article is to describe the importance of including a
      diagnostic play session as a major component of a comprehensive psychiatric
      assessment of young children. It is through observing a young child's play that a
      clinician can gather a wealth of information about a child's developmental level
      in the cognitive, social, language, and motor domains as well as some insight
      into the development of a child's personality and inner world. This data combined
      with the results of developmental testing, school observations, and parent
      interviews can be important in making formulations and diagnoses and planning
      strategies for interventions.

PMID- 10202589
TI  - Medical assessment. Its role in comprehensive psychiatric evaluation.
AB  - This article describes the role of a medical evaluation in the overall
      developmental assessment of a young child. General guidelines for conducting the
      evaluation and practical issues to consider in dealing with young children and
      their families are provided. To illustrate these points, hypotonia and failure to
      thrive, two broad categories of pathology with numerous potential underlying
      medical causes, are addressed specifically. The involvement of genetics in
      developmental pathology is also outlined in some detail. Finally, issues to be
      aware of when considering pharmacologic management of psychiatric symptoms in
      young children are discussed.

PMID- 10202590
TI  - Obtaining and formulating a developmental history.
AB  - Obtaining a detailed developmental history from caregivers is essential to
      comprehensive assessment. This article describes the goals and characteristics of
      caregiver interviewing, and provides suggestions for integrating data with other
      sources. Several specific areas of exploration are identified.

PMID- 10202591
TI  - Assessment of caregiver-child interaction in the context of a preschool
      psychiatric evaluation.
AB  - Assessment of the caregiver-child relationship has become an intrinsic part of
      the preschool child psychiatric evaluation. Normal and abnormal development of
      relationship is influenced by a myriad of genetic, psychological, cultural, and
      environmental factors in both the caregiver and the young child. In the past,
      professionals from different fields, like pediatrics, neurology, development, and
      social welfare, would understand the child and his or her environment with their
      own tools. Since then, these parallel lines have converged into a more
      complementary and integrated view. The need to evaluate the caregiver, the child,
      the caregiver-child interaction, and the context of the relationship makes the
      evaluation a challenging multidisciplinary process, in which standardized
      assessment tools have to be integrated into a sound clinical conceptualization of
      the evaluated relationship.

PMID- 10202592
TI  - Assessing speech, language and communication.
AB  - This article discusses the assessment of communication skills in children from
      birth to 5 years of age. The different methods appropriate for different
      developmental levels and the relationship of collateral areas, such as hearing,
      cognition, and speech motor control to the communication process, are addressed.
      The need for standardized and informal measures is emphasized. Case studies are
      presented to illustrate the principles outlined.

PMID- 10202593
TI  - Physical and occupational therapy.
AB  - Occupational and physical therapists are concerned with an infant's ability to
      perform in object play and manipulation, self-care, mobility, and social
      function. Within the realm of child psychiatry, occupational and physical
      therapists contribute to a comprehensive assessment by providing in-depth
      neuromotor, sensory processing, and functional or adaptive skill analyses. The
      three theoretic approaches presented in this article represent the current trends
      within infant and young child assessment in the fields of occupational and
      physical therapy. In the past, therapists primarily used neuromotor or
      developmental assessments. Although these assessments have proven to be adequate
      for discrimination between children with developmental delays and those who are
      typically developing, they have not been as useful in documentation of progress
      in treatment or in providing an understanding of qualitative aspects of movement.
      Qualitative assessments that are more sensitive to change and to the complexity
      of functional skills have grown with the development of more sophisticated early
      intervention strategies. Assessments based on dynamic systems theory allow
      therapists to quantify abilities, document subtle changes over time, and provide
      information on the qualitative aspects of movement. Therapists, however, continue
      to regularly employ assessments from multiple theoretic approaches to complete
      comprehensive evaluations.

PMID- 10202594
TI  - Collaboration and teamwork in assessment for early intervention.
AB  - Interdisciplinary teamwork and collaboration in early intervention require that
      professionals adopt a common set of developmentally appropriate standards that
      guide the major activities of screening, diagnostic assessment, individualized
      curriculum planning, progress and program evaluation, and family-centered
      services. This article has reviewed the common roadblocks to effective teamwork,
      especially among educational and medical professionals. As solutions to the
      typical problems in collaboration, eight developmentally appropriate standards
      ensure best practice and adherence to the Individuals with Disabilities Education
      Act mandates: utility, acceptability, authenticity, equity, sensitivity,
      convergence, congruence, and collaboration.

PMID- 10202595
TI  - Systems for collaboration. Integrating multiple perspectives.
AB  - A number of suggestions have been offered for those who choose to collaborate
      with other professionals for comprehensive, interdisciplinary assessments of
      young children and their families. A systems perspective was used to emphasize
      the interrelatedness of different disciplines as well as the complex nature of
      relationships. (For a specific description of the professionals and their roles
      and responsibilities on early childhood assessment teams, please refer to the
      individual contributions by disciplinary representatives in this issue.) Whether
      long-established teams or loosely formed community coalitions, professionals
      working together can both improve and expand their services to children through
      collaboration. Although collaboration is not always easy and is certainly time
      consuming, the rewards are great both for individual professionals and the young
      children and families served. Just like the long hours and often tedium of
      practicing for a musical performance, once the stage is set and the lights come
      on, a sort of magic occurs. Unlike an orchestra, however, at any time any member
      can take up the baton and lead a team to increased collaboration and improved
      patient services. Each member must excel not only on an individual instrument,
      but in integrating that skill with every other player. In this article, some
      strategies have been offered for professionals in conducting their
      interdisciplinary services and in leading collaborative efforts.

PMID- 10202596
TI  - Developmental and psychiatric evaluation in the preschool context.
AB  - This article documents the ways in which a school-based developmental evaluation
      can be an effective and powerful alternative to the traditional clinic-based
      evaluation. The child is not taken to a strange new place but observed and
      evaluated in his or her naturalistic environment. The families have increased
      access to care, and the foundation is laid for cohesive, trusting working
      relationships with families and teachers. Children are evaluated in one of two
      models or a combination of both naturalistic observation and individual direct
      assessment. Tensions between the clinical and educational system exist, but the
      early childhood evaluator who educates himself or herself about the cultures and
      forces at work can build from the strengths of each system to effect positive
      growth for young children at risk for developmental delays or psychiatric
      disorders.

PMID- 10202597
TI  - Evaluation of early childhood programs.
AB  - Unlike kindergartens for 5-year-old children, which are taken for granted,
      preschool programs for 3- and 4-year-old children are accepted tentatively in the
      United States, making them ideal candidates for evaluative research. Evaluative
      research compares the performance of program participants either with ideal
      performance, the performance of other children in general, or the performance of
      children who did not attend early childhood programs. Evaluative research
      assesses and compares child and family outcomes, after equalizing child and
      family background characteristics by design or statistical analysis and taking
      program characteristics into account. Evaluative research is either ideal-program
      research, typical program research, or specific-program evaluation. Ideal-program
      research has provided evidence of the value of ideal preschool programs. Typical
      program research, however, has shown how far from ideal actual programs are, and
      thus sets the context for specific-program evaluations. Done well, such
      evaluations can improve school, Head Start, and child care early childhood
      programs by focusing the attention of teachers, parents, and other stakeholders
      on program processes and children's development.

PMID- 10202598
TI  - Culturally sensitive assessment.
AB  - Issues of cultural interaction and culturally sensitive assessment and treatment
      of young children have become prominent in recent years for mental health
      professionals, for reasons having to do with changing demographics, public
      values, and professional vision. "Culture" refers to the sociocultural adaptation
      of design for living shared by people as members of a community. Mental health
      professionals who work with culturally diverse populations need to become
      culturally self-aware and find abstract and experiential ways to build a useful
      body of professional knowledge concerning childrearing and discipline practices,
      health and illness beliefs, communication styles, and expectations about family
      or professional relations or other group interactions. They also need to learn
      how to work effectively in intercultural teams, use families as partners and
      resources, train and work with interpreters, and select and use formal and
      nonformal assessment procedures in appropriate, culturally sensitive ways.

PMID- 10202599
TI  - Mental health assessment of young children in a managed care environment.
AB  - Managed behavioral health care is widely perceived as a threat to traditional
      practice in mental health at the expense of quality care. Although such
      assertions by mental health providers may prove to be justified in certain
      circumstances, they should not serve to obscure the quite reasonable public
      health motives behind managed care and the favorable effect managed care
      organizations may ultimately have on clinical decision-making and practice. By
      compelling practitioners to more clearly articulate the basis for their clinical
      judgments and by increasingly requiring evidence to support such judgments, they
      discourage the application of ill-considered, sometimes inappropriate, and
      occasionally iatrogenic evaluation and treatment interventions. In the future,
      there is significant danger that developmental assessment and treatment
      procedures for young children will be inappropriately constrained and diminished.
      This is especially true if those who work with young children fail to use the
      tools available to them to make the case for the best of current practice,
      whether a clearly stated clinical rationale, a formal appeal, the advocacy of our
      health professions, or applied clinical services research. The practices of our
      health plans need to be understood by providers in the context of managed care
      values. Primitive systems should not be confused with corrupt systems. Although
      undoubtedly the latter exist, they do not necessarily predominate. Within a
      managed care context and with due respect to managed care assumptions, it is
      possible to bring utilization management and contemporary practices in
      developmental assessment into closer alignment, ultimately to the benefit of
      children who need them.

PMID- 10202600
TI  - Cyclosporine A neurotoxicity among bone marrow transplant recipients.
AB  - Cyclosporine A (CsA) neurotoxicity is an iatrogenic disease with significant
      morbidity and occasional mortality. We retrospectively reviewed the cases of CsA
      neurotoxicity among bone marrow transplant recipients at our institution, and
      summarized the current literature on the subject. The neurologic presentation is
      varied and the neurologic manifestations are reversible, even after prolonged
      toxicity, in most instances. Serum CsA level is useful in evaluation, as the
      level is high in most instances. However, in a case of suspected neurotoxicity,
      withdrawal of the drug is the only way of determining presence or absence of such
      toxicity. The electrophysiologic studies, especially electroencephalogram (EEG),
      is very sensitive in identifying the problem, but lacks specificity. On the other
      hand, the neuroimaging studies are helpful in making a diagnosis if they show
      characteristic findings of hyperintense lesions affecting posterior cerebral
      regions on T2 weighted magnetic resonance images (MRI) or white matter
      hypodensities on computed tomographic (CT) scan. These lesions are probably due
      to breakdown of blood-brain barrier resulting in leakage of fluid in interstitial
      space. The breakdown could be serious enough to cause microhemorrhages that may
      coalesce to produce macrohemorrhages.

PMID- 10202601
TI  - Controlled release levodopa in Parkinson's disease: influence of selection
      criteria and conversion recommendations in the clinical outcome of 450 patients.
      STAR Study Group.
AB  - We present the results of an open, prospective, multicentric study including 450
      patients with mild to moderate Parkinson's disease (PD) converted from standard
      Sinemet to Sinemet CR (controlled release; Dupont Pharma, Pavia, Italy). Patients
      with complex fluctuations and diphasic dyskinesias were excluded and the
      conversion was made after some recommendations, depending on the clinical
      problems and the daily dosage and administration schedule of standard (STD)
      Sinemet. The condition of more than 60% of the patients improved after the change
      and 80% of them preferred the CR formulation by the end of the study. We found a
      moderate, but significant, improvement in most of the efficacy parameters used,
      such as the Unified Parkinson's Disease Rating Scale (UPDRS), the Schawb and
      England scale, and dyskinesias and sleep questionnaires. Forty-five patients
      (10%) discontinued the study due to adverse effects (mainly gastrointestinal
      disturbances, functional deterioration, and dyskinesias). We conclude that
      Sinemet CR is a useful and safe therapeutic option in patients with mild and
      moderate PD. Selection of the patients is the most important outcome factor.

PMID- 10202602
TI  - Comparison of the effects of vigabatrin, lamotrigine, and topiramate on
      quantitative EEGs in patients with epilepsy.
AB  - Information on the effects of newer antiepileptic drug (AEDs) on the
      electroencephalogram (EEG) is sparse and contradictory. Quantitative EEG (qEEG)
      provides a method of estimating the effects of drugs on the central nervous
      system. Twenty-three adult patients with difficult-to-control complex partial
      seizures, with or without secondary generalization, participated in an add-on
      study with one of three newer AEDs: vigabatrin (n = 10), lamotrigine (n = 6), and
      topiramate (n = 7). Frequency analysis and topographic mapping of awake EEGs
      before and during treatment with the drug were compared. Statistical analysis was
      performed using 2-way analysis of variance (ANOVA) with repeated measures.
      Vigabatrin administration was followed by a diffuse decrease in the absolute
      alpha (p < 0.05) and beta (p < 0.02) activities and a decrease in the absolute
      theta in the frontal and parieto-occipital regions (p < 0.03). Lamotrigine caused
      a significant diffuse increase in the faster frequencies (relative alpha p < 0.04
      and relative beta p < 0.02), and decrease in the slower activities (relative
      theta in the posterior head regions p < 0.03 and relative delta diffusely p <
      0.05). Topiramate increased the absolute beta (p < 0.05) and theta (p < 0.02)
      activities diffusely and decreased the relative alpha activity over the left
      hemisphere (p < 0.03). The different effect profiles of the newer AEDs on the
      electrical brain activity may reflect their different mechanisms of action.

PMID- 10202603
TI  - Hiccup and apparent myoclonus after hydrocodone: review of the opiate-related
      hiccup and myoclonus literature.
AB  - The author recently encountered a patient with hiccups, intermittently
      accompanied by apparent focal rhythmic diaphragmatic myoclonus after hydrocodone
      administration. Review of the literature disclosed a paucity of previous reports
      of hiccup, but many reports of myoclonus after opiate administration. A wide
      variety of opiates and routes of administration have been implicated, but high
      doses and the presence of other agents (antipsychotics, antiemetics, nonsteroidal
      antiinflammatory agents, antidepressants) may pose special risks. Review of the
      literature suggests three types of opiate-related myoclonus. Opiate-induced
      myoclonus (OIM) is often generalized and is either periodic or associated with
      rigidity. Opiate-induced myoclonus frequently occurs in the context of underlying
      medical conditions, D2 antagonist coadministration, or other drugs (nonsteroidal
      anti-inflammatory agents, antidepressants), and usually responds to either
      naloxone or benzodiazepines. Intrathecal OIM has not been linked to D2 antagonist
      coadministration or benzodiazepine responsiveness but may be associated with non
      steroidal antiinflammatory agents. Opiate withdrawal myoclonus may be stimulus
      sensitive, associated with D2 antagonist coadministration, and responsive to
      benzodiazepines and unresponsive to naloxone. There are several problems in
      interpreting the literature, and more study is needed. Opiatergic, serotonergic,
      dopaminergic, and other mechanisms are considered.

PMID- 10202604
TI  - Effects of female sex steroids on Parkinson's disease in postmenopausal women.
AB  - There are conflicting reports about estrogen modulating the activity of
      nigrostriatal dopaminergic neurons. Furthermore, modulation may be influenced by
      progesterone levels. Therefore, the clinical effects of sex steroids on
      parkinsonian symptoms in postmenopausal women with Parkinson's disease (PD) were
      analyzed in the present study. Patients (n = 12) were under the age of 80, able
      to perform the motor function tests, and showed no contraindications for estrogen
      suppletion. Motor function was assessed using the Unified Parkinson's Disease
      Rating Scale (UPDRS) and a patient interview on subjective changes. In a placebo
      controlled, randomized, double-blind trial lasting 8 weeks, no significant
      dopaminergic effect of estradiol (E2) could be demonstrated, whereas in an open
      trial phase lasting 2 weeks, progesterone seemed to have an antidopaminergic
      effect. Several mechanisms are discussed that can account for the fact that we
      found no effect of E2 on motor functioning in our patients with PD.

PMID- 10202605
TI  - The impact of clozapine treatment on serum lipids in chronic schizophrenic
      patients.
AB  - The aim of this retrospective study is to determine whether lipid levels rise in
      neuroleptic-resistant chronic schizophrenic patients during clozapine treatment
      and if this rise is correlated with a decrease in aggressive and suicidal
      behavior. Seventy neuroleptic-resistant schizophrenic patients treated with
      clozapine for at least 6 months were compared with 30 chronic schizophrenic
      patients treated with classic antipsychotic agents for the same length of time.
      Data on serum levels of cholesterol and triglycerides and on aggressive and
      suicidal behavior, as measured by the Overt Aggression Scale (OAS), were
      collected in both groups before treatment and 6 months later. A significant
      reduction in aggressive and suicidal behavior was noted in the clozapine-treated
      group but not in the classical antipsychotic-treated group. Clozapine treatment
      was associated with an elevation in serum triglyceride level, whereas classic
      antipsychotic treatment was associated with an increase in serum cholesterol
      level. We conclude that serum cholesterol level does not play a role in the
      clozapine-induced attenuation in aggressive and suicidal behavior in neuroleptic
      resistant schizophrenic patients, though the accompanying elevation in
      triglycerides may be relevant to a behavioral effect.

PMID- 10202606
TI  - Intravenous loading of valproate for epilepsy.
AB  - Valproate is an antiepileptic drug that has broad spectrum activity against
      several types of seizure. Little information is available about the use of
      valproate for acute loading of patients when a rapid increase in serum level is
      needed. We describe the use of intravenous valproate in 20 adults with epilepsy.
      In each case, a loading dose was calculated by multiplying the patient's body
      mass, desired change in serum level, and estimated volume of distribution. The
      mean dose (+/- SD) administered was 1420 +/- 440 mg (19.4 +/- 5.4 mg/kg). In four
      patients, the dose was infused at 20 mg/min; in all other patients, infusions
      were performed at 50 mg/min. The infusions were tolerated well and few clinical
      side effects were observed. Postinfusion levels were drawn and the apparent
      volume of distribution was calculated to be 0.22 +/- 0.04 L/kg. The results
      indicate that intravenous valproate may be used to quickly and efficiently
      increase serum levels in patients with epilepsy.

PMID- 10202607
TI  - Cytokine production in panic disorder patients.
AB  - Based on findings that stress and anxiety may modulate immune function, we
      compared the production of interleukin-2 (IL-2) and interleukin-3 (IL-3) by
      peripheral blood mononuclear cells between 24 patients with nonmajor depressed
      panic disorders, 9 with agoraphobia and 15 without, and 19 healthy volunteers. No
      differences in the production of these cytokines was noted between the patients
      with panic disorders and the volunteers or between the patients with and without
      agoraphobia. However, in the patients, a negative correlation was found for
      interleukin-3 production with severity of state anxiety, but not with trait
      anxiety or depression. This finding indicates that interleukin-3 levels may be
      sensitive to the presence of anxiety and stress.

PMID- 10202608
TI  - 3H-spiperone binding to lymphocytes in neuroleptic-naive-schizophrenia and the
      effect of neuroleptic treatment.
AB  - The aim of this study was to determine whether spiperone binding to lymphocytes
      could serve as a biological marker of susceptibility to schizophrenia and
      schizophrenic spectrum disorders or as a measure of response to neuroleptic
      treatment. Lymphocyte spiperone binding parameters (Bmax, KD) were assessed in 13
      patients with schizophrenia and 4 patients with schizotypal personality disorder,
      all neuroleptic naive, and in 19 age- and sex-matched control subjects. A
      repeated determination was carried out in 11 of the schizophrenic subjects after
      several months of neuroleptic treatment. In addition, the binding characteristics
      of 12 of the schizophrenic/schizotypal patients were compared with those of 13
      healthy family members and normal unrelated controls. No significant differences
      were detected between the schizophrenic subjects and controls before or after
      neuroleptic treatment or between the patients and their non-affected family
      members and controls.

PMID- 10202609
TI  - Tremorlytic activity of budipine in Parkinson's disease.
AB  - To objectively quantify the tremorlytic activity of budipine in Parkinson's
      disease (PD), we performed long-term tremor recordings in addition to the
      Columbia University Rating Scale (CURS) in a subset of patients (n = 14) who
      enrolled in a multicenter, double-blind, placebo-controlled study. Tremor
      occurrence improved in the budipine group (n = 7) from 24.7 +/- 15.5% to 14.8 +/-
      14.5% (p < 0.05). Tremor intensity decreased from 9.1 +/- 2.5 (signal-to-noise
      ratio) to 7.2 +/- 1.6. The CURS sum score improved from 5.7 to 3.0 in the
      budipine group, whereas there was only a small improvement in the placebo group
      (from 7.1 to 5.5). These data suggest that budipine is an effective tremorlytic
      agent in PD and that it may be used as an alternative to anticholinergics.

PMID- 10202610
TI  - Transdermal scopolamine withdrawal syndrome.

PMID- 10202611
TI  - Bronchoalveolar lavage in lung transplantation. State of the art.
AB  - Fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) has become a crucial
      tool in the management of lung transplant recipients. Detection of pulmonary
      infectious pathogens by culture, cytology, and histology of BAL, protected brush
      specimens, and transbronchial biopsies (TBB) is highly effective. Morphologic and
      phenotypological analyses of BAL cells may be suggestive for certain
      complications after lung transplantation. For interpretation of BAL findings, the
      natural course of BAL cell morphology and phenotypology after lung
      transplantation must be considered. During the first 3 months after pulmonary
      transplantation, elevated total cell count in BAL and neutrophilic alveolitis are
      common, representing the cellular response to graft injury and interaction of
      immunocompetent cells of donor and recipient origin. With increasing time after
      transplantation the CD4/CD8 ratio decreases due to lowered percentages of CD4
      cells in BAL. During bacterial pneumonias, the cellular profile of BAL is
      characterized by a marked granulocytic alveolitis. Lymphocytic alveolitis with a
      decreased CD4/CD8 ratio is suggestive of acute rejection, but is also found in
      viral pneumonias and obliterative bronchiolitis. In the case of a combined
      lymphocytosis and neutrophilia without any evidence of infection, obliterative
      bronchiolitis should be considered. Functional analyses of BAL cells can give
      additional information about the immunologic status of the graft, even before
      histologic changes become evident but have not been established in routine
      transplant monitoring. However, functional studies suggest an important role of
      activated, alloreactive and donor-specific T lymphocytes in the pathogenesis of
      acute and chronic lung rejection. Investigations of soluble components in BAL
      have given further insight into the immunologic processes after lung
      transplantation. In this overview, the characteristics of BAL after lung
      transplantation will be summarized, and its relevance for the detection of
      pulmonary complications will be discussed.

PMID- 10202612
TI  - HLA-identical sibling renal transplantation--a 21-yr single-center experience.
AB  - Human lymphocyte antigen (HLA)-identical sibling organs offer the best long-term
      outcomes for recipients of a renal transplant apart from an identical twin.
      Unlike cadaveric transplants, however, factors that affect long-term survival of
      these immunologically privileged grafts are not well described. We reviewed 108
      HLA-identical transplants performed at our institution between January 1977 and
      February 1993. Variables chosen for graft survival analysis were: gender, age and
      ABO blood type of donors and recipients, panel reactivity antibodies (PRA), blood
      transfusions prior to transplant, pregnancies, and the underlying renal disease.
      Additionally, incidence of acute rejection (AR), timing of AR, serum creatinine
      levels at 1 wk and at 1 yr, and presence of hypertension were included in the
      analysis. Mean follow-up was 130.9 +/- 58.2 months (range 38-250 months). Actual
      5-yr patient and graft survivals were 92 and 88%, respectively. Thirty-eight
      grafts were lost, and 22 recipients died during the observation period. Death was
      the main cause of graft failure. Cardiac events accounted for the majority of
      deaths. AR occurred in 46% and repeated rejections in 11% of recipients.
      Actuarial graft survival at 10 yr was poorer for patients with any AR (69%), and
      significantly worse with repeated AR (33%), compared to patients without AR
      (86%), p = 0.001). Sixty percent of all rejections and 88% of the first
      rejections occurred in the first 60 d post-transplantation. The first AR that
      occurred after 60 d was associated with poor graft survival (49 vs. 70%, p =
      0.04). Recipients with renal diseases with potential to recur (membranous
      glomerulonephritis (MGN), membrano-proliferative glomerulonephritis (MPGN), focal
      and segmental glomerulonephritis (FSGN), polyarteritis nodosa (PAN), rapid
      progressive glomerulonephritis (RPGN), Henoch-Schoenlein purpura (HSP), diabetes
      mellitus (DM), interstitial nephritis, systemic lupus erythematosus (SLE) and
      chronic glomerulonephritis (CGN)) faired worse as a group than recipients with
      hypertensive nephrosclerosis (HTN), autosomal dominant polycystic kidney disease
      (ADPKD), Alport's, reflux or congenital dysplasia (68 vs. 96% at 10 yr, p =
      0.0009). Poor patient survival was seen in diabetics (71 vs. 88% at 10 yr, p =
      0.01). There was a trend to poorer graft survival in diabetic recipients when
      compared to non-diabetics (65 vs. 81% at 10 yr, p = 0.054). Elevated creatinine
      at 1 yr was associated with worse graft survival. Likewise, the magnitude of
      creatinine increase during the first year directly correlated with the risk of
      graft loss. Hypertensive patients were more likely to lose their grafts than
      normotensive recipients (72 vs. 86%, p = 0.04). Pre-transplant blood transfusion,
      pregnancy, and PRA level were not associated with increased graft failure or AR.
      Graft survival was not affected by gender, age, or ABO blood type of donors or
      recipients. In conclusion, better prevention and treatment of AR, hypertension,
      and cardiac disease should improve graft and patient survival. Close attention to
      recurrence of disease and subtle changes in the creatinine level during the first
      year might dictate early diagnostic and, hopefully, therapeutic interventions.

PMID- 10202613
TI  - Pre-transplant identification of risk factors that adversely affect length of
      stay and charges for renal transplantation.
AB  - BACKGROUND: In the current era of renal transplantation, increasing attention is
      being focused on resource utilization. The purpose of this study was to identify
      demographic, medical and immunologic risk factors that are associated with
      changes in length of stay (LOS) and charges for renal transplantation. METHOD:
      The study was a retrospective analysis of 311 consecutive renal transplants
      performed at a single institution. Univariate and multivariate analyses were used
      to examine relationships between risk factors, LOS, charges and post-operative
      complications. RESULTS: The following pre-transplant variables were found to be
      independently significant in predicting increased LOS and/or charges: African
      American race, obesity for women, chronic obstructive pulmonary disease (COPD),
      presence of cardiac disease or previous stroke, pre-transplant dialysis time > or
      = 1 yr, a 10% increase in panel reactive antibody (PRA), cadaver donor and
      retransplantation. The analyses were performed with and without adjustment for
      key outcome variables such as delayed graft function (DGF) and use of induction
      antibody therapy. Increased LOS or charges for specific risk factors could be
      attributed to increased complication rates, including delayed graft function seen
      with various co-morbidities, or increased immunologic risk and more frequent use
      of induction antibody therapy. CONCLUSION: Analysis of linked financial and
      clinical databases can reveal demographic, medical and immunologic risk factors
      that correlate with LOS, charges and complications for renal transplantation.
      Efforts to establish quantitative relationships for various risk factors relative
      to resource utilization will become important in managed care and/or capitated
      healthcare delivery systems.

PMID- 10202614
TI  - The impact of (1:1) cyclosporine A conversion to its microemulsion formulation on
      the kidney function of patients with cardiac allografts.
AB  - Due to the large variations in the absorption and bioavailability of conventional
      cyclosporine A (CyA), 1:1 (mg:mg) conversion to its microemulsion formulation
      (Neoral) has been advocated in transplant recipients. However, the renal hazards
      and biochemical effects of such conversions and not known in cardiac transplant
      recipients. In this study, 68 cardiac transplant recipients who were receiving
      conventional CyA, for a period of 61.3 +/- 36.0 (mean +/- standard error (SE))
      months, were switched to the microemulsion formulation (Neoral). The biochemical
      and renal function tests were evaluated at 1, 3, 6, 9 and 12 months pre- and post
      conversion of CyA. The results obtained post-conversion were compared with those
      of the baseline (pre-conversion). Serum creatinine and uric acid levels
      significantly increased post-conversion to the microemulsion formulation. One
      patient required discontinuation of the microemulsion in an attempt to reverse
      severe renal failure. In spite of a significant decrease in the microemulsion
      dose at 6, 9 and 12 months, there was a significant increase in the whole blood
      CyA trough levels at 9 and 12 months of conversion. There was no significant
      change in blood pressure, serum total cholesterol or potassium post-conversion.
      Our results suggest that after 1:1 (mg:mg) conversion of CyA to its microemulsion
      formulation, there will be a significant rise in serum creatinine, uric acid and
      whole blood trough CyA levels necessitating significant dose reduction. This
      effect is probably due to the markedly improved absorption and bioavailability of
      the latter.

PMID- 10202615
TI  - Male recipients of kidneys from female donors are at increased risk of graft loss
      from both rejection and technical failure.
AB  - The aim of the present retrospective study was to uncover the factor(s)
      responsible for the poor outcome of cadaver kidney grafts from female donors in
      male recipients. The 741 transplantations performed at our center from August
      1983 to September 1997 were distributed into four groups according to recipient
      and donor gender: female donor to female recipient (F to F: n = 117), male donor
      to female recipient (M to F: n = 172), female donor to male recipient (F to M: n
      = 170), and male donor to male recipient (M to M: n = 282). All the patients
      received immunosuppressive therapy based on corticosteroids and cyclosporine,
      associated or not with either azathioprine or prophylactic anti-lymphocyte
      globulin. Overall graft survival was lower in the F to M group than in the three
      other groups (p = 0.009). Failures due to rejection were more frequent during the
      1st post-transplant trimester in female than in male donor grafts, irrespective
      of recipient gender (p = 0.025). All failures due to technical problems occurred
      during the first 3 months post-transplantation: they were more frequent in the F
      to M group than in the three other groups (p = 0.040): this could be related to
      the older age of the donors in the former group. After the first post-transplant
      year, failures due to causes other than rejection remained low in the F to F
      group but increased steadily in the three other groups (p = 0.007). Specific
      survival rates were not correlated with the time-evolution of mean serum
      creatinine values, daily doses and trough levels of cyclosporine in the four
      groups of grafts. In conclusion, the poor outcome of F to M grafts results from
      combined immunologic and technical factors exerting their effects early in the
      course of transplantation.

PMID- 10202616
TI  - Prospective study of microchimerism in transplant recipients.
AB  - BACKGROUND: We evaluated peripheral blood microchimerism in 48 consecutive organ
      transplant recipients (35 kidneys, ten livers, one kidney-liver, one kidney
      pancreatic islet, one kidney pancreas) up to 12 months post-transplantation.
      Patients were categorized according to the presence or absence of rejection
      episodes, and the patterns of microchimerism in the two groups were then
      compared. METHODS: DNA was extracted from donor, pre-transplant, and post
      transplant peripheral blood samples. Several polymerase chain reaction (PCR)
      based assays were developed for the detection of microchimerism. Assay
      sensitivities ranged from 0.0001 to 3%. RESULTS: Microchimerism was detected only
      in sex-mismatched cases (male donors and female recipients) using nested PCR for
      a Y-chromosome marker. There were ten such cases (six kidneys, two livers, and
      two combined organ transplants). In patients without rejection (n = 7), there was
      a peak of donor-DNA at 1-3 wk post-transplantation followed by a second peak
      between 3 wk and 4 months. In patients with biopsy-proven rejection (n = 3), the
      peaks were absent and the levels of microchimerism were extremely low (< 0.001%).
      Microchimerism levels declined in all 10 patients and were barely detectable 1 yr
      post-transplantation. Microchimerism was not detected in the remaining 38
      patients despite using a battery of sensitive PCR-based assays. CONCLUSIONS: In
      our study, microchimerism was detected using the Y-chromosome PCR assay only and
      the level of donor-DNA in a given patient varied over time. This study highlights
      the difficulties in establishing a correlation between microchimerism and
      transplant tolerance.

PMID- 10202617
TI  - Improving the therapeutic monitoring of cyclosporin A.
AB  - The narrow therapeutic window of cyclosporin A (CsA) and the variable
      pharmacokinetics of the traditional preparation, CsA-SIM (Sandimmune), have made
      it difficult to establish its optimal use. The introduction of a microemulsion
      preparation, CsA-ME (Neoral), with less variable pharmacokinetics, has made it
      possible to attempt to define its use more closely. One hundred and one renal
      allograft recipients were converted from CsA-SIM to CsA-ME. Absorption was
      monitored using a standard pharmacokinetic 'profile' measuring 'whole blood' CsA
      levels at several time points following drug administration. Areas under the
      resulting time-versus-CsA concentration curve (AUC) were calculated.
      Surprisingly, many patients showed very little fluctuation in 'whole blood'
      levels after administration of the conventional preparation: 31% had a difference
      between trough (to) and maximal levels of < 100 micrograms/L. On microemulsion
      cyclosporin, there was much better correlation between AUC and several parameters
      incorporating elements of trough and peak values. The best correlation was with
      t0 + (t1/4), where t1 represents the concentration at 1 h following
      administration, (r2 = 0.779 for microemulsion cyclosporin). The use of this
      parameter is a practical possibility in an out-patient setting. The very common,
      but under-recognised, pattern of almost flat absorption profiles in patients on
      conventional CsA suggests that the use of CsA in numerous clinical contexts
      should be reviewed, since CsA immunosuppression may previously have been
      inadequately monitored.

PMID- 10202619
TI  - Erythropoietin to prevent and treat the anemia of prematurity.
AB  - Human recombinant erythropoietin was first cloned in 1985, and is currently
      available for clinical use for a variety of anemias. Following successful
      clinical trials using erythropoietin to treat adults with the anemia of end-stage
      renal disease, the first clinical trial evaluating the use of erythropoietin in
      preterm infants to treat anemia was published in 1990. Since that initial report,
      numerous clinical trials have reported various levels of success in the treatment
      of this anemia. Most recently, erythropoietin has been used in the first weeks of
      life in an attempt to prevent the anemia of prematurity. This review describes
      mechanisms of erythropoiesis in the fetus and neonate, and focuses on recent
      clinical trials evaluating the use of erythropoietin to prevent and treat anemia
      in preterm infants.

PMID- 10202618
TI  - Expression of gamma-IFN mRNA in bronchoalveolar lavage fluid correlates with
      early acute allograft rejection in lung transplant recipients.
AB  - Various cytokines are upregulated in acute allograft rejection (AR). Local
      production of Th-1 cytokines is suggested to play a pathogenic role in AR, and Th
      2 cytokines in the development of allograft tolerance. The purpose of this study
      was to correlate the expression of Th-1 [interleukin-2 (IL-2) and gamma
      interferon (gamma-IFN)], and Th-2 [interleukin-10 (IL-10)] cytokines in
      bronchoalveolar lavage (BAL) fluid with AR in lung transplant (LT) recipients.
      The role of Th-1 dominance expressed as IgG2/IgG1 ratio in BAL in AR was also
      examined. The mRNA expression for IL-2, gamma-IFN and IL-10 was examined in 64
      BAL specimens from 23 LT recipients using reverse transcriptase-polymerase chain
      reaction (RT-PCR). IgG1 and IgG2 levels were measured in 55 BAL specimens by
      enzyme-linked immunosorbent assay (ELISA). The expression on mRNA for these
      cytokines, and the ratio of IgG2/IgG1 was correlated with AR (early AR occurring
      within 3 months of transplant and late AR occurring after 3 months). Ten patients
      had 17 episodes of biopsy proven AR. Twelve episodes of AR (6 patients) occurred
      within the first 3 months of transplantation. In 5 patients, AR was diagnosed 4,
      5, 6, 9 and 24 months post-transplantation. Detection of gamma-IFN mRNA
      correlated significantly with early AR (p < 0.001), whereas it lacked correlation
      with late AR. Expression of IL-2 and IL-10 mRNA did not correlate with AR. IL-10
      was present in most samples irrespective of the presence or absence of AR. The
      ratio of IgG2/IgG1 was similar in patients with or without AR. Our findings
      suggest that the detection of gamma-IFN mRNA in BAL by RT-PCR is useful for
      immune monitoring of early AR in LT recipients. Absence of elevated IgG2/IgG1
      ratio, and presence of IL-10 in BAL during AR suggests that Th-1 cytokines may
      not be the sole mediator of rejection in LT recipients.

PMID- 10202620
TI  - Requirements for long-chain polyunsaturated fatty acids in the preterm infant.
AB  - Dietary long-chain polyunsaturated fatty acids have demonstrable beneficial
      effects on early development. The effects on neural development are of particular
      interest. Human milk is the best and only time-proven source of fat and essential
      fatty acids in the infant diet. Technologic procedures based on chemical and
      physical separation of the unsaturated fatty acids have permitted the isolation
      of concentrated sources of docosahexaenoic acid and arachidonic acid for clinical
      use. Virtually all infant formulas in developed countries have increased the
      levels of gamma-linolenic acid, and several manufacturers in Europe and in Japan
      have added docosahexaenoic acid, or docosahexaenoic acid plus arachidonic acid,
      or have also included gamma-linolenic acid in formulas for preterm and term
      infants. The efficacy of this practice for preterm infants seems fairly well
      established. The use of stable isotope methods to evaluate biosynthesis of long
      chain polyunsaturated fatty acids from dietary precursors may help to better
      define optimal amounts and relationships of fatty acids in infant formula.

PMID- 10202621
TI  - Recent developments in inhaled nitric oxide therapy of the newborn.
AB  - Inhaled nitric oxide therapy improves oxygenation and reduces the need for
      extracorporeal life support in near-term and term newborns with hypoxemic
      respiratory failure and persistent pulmonary hypertension of the newborn.
      Previous studies demonstrated that the efficacy of inhaled nitric oxide therapy
      is related to the underlying disease associated with persistent pulmonary
      hypertension and that lung recruitment strategies augment the response to this
      inhalational vasodilator. This review of recent studies evaluates new insight
      into important questions regarding the optimal dose of inhaled nitric oxide,
      potential adverse effects associated with inhaled nitric oxide therapy, and the
      potential role of inhaled nitric oxide in the premature newborn with hypoxemic
      respiratory failure.

PMID- 10202622
TI  - Current status of liquid ventilation.
AB  - Perfluorochemical liquid has been used experimentally to enhance mechanical
      ventilation for the past 30 years. Liquid ventilation is one of the most
      extensively studied revolutionary medical therapies being considered for use in
      practice. Since 1989, when the first human neonates were treated with
      perfluorochemical liquid, more than 500 human patients--neonate, pediatric, and
      adult--have been treated with liquid ventilation as part of clinical trials.
      However, most of the clinically relevant information known to the medical field
      about liquid ventilation still comes from the laboratory. This paper seeks to
      briefly present current information available from studies involving liquid
      ventilation, both laboratory-based and clinical trials, as well as to inform the
      reader on patient management. In addition, we attempt to elucidate future
      directions.

PMID- 10202623
TI  - Recent advances in renal development.
AB  - Anatomical development of the kidney is achieved by the reciprocal induction of
      the ureteric bud and the metanephric mesenchyma. This interaction triggers the
      process of nephrogenesis and culminates in the formation of the mature kidney. In
      vivo, nephrogenesis is coordinated with renal vascularization. In fact, vascular
      precursors, epithelial progenitors, and mesenchymal cells communicate with one
      another in a highly organized fashion. As a result of this complex interaction, a
      mature kidney, architecturally and functionally ready for extrauterine life, is
      produced. This review deals with the relevant molecules and mechanisms governing
      nephrovascular development.

PMID- 10202624
TI  - Renal cystic disease.
AB  - Renal cystic diseases constitute the most common genetic cause for end-stage
      renal disease in children and young adults. Recently, there has been rapid
      progress regarding the identification or chromosomal localization of some of the
      responsible disease genes. Studies of the respective gene products and of related
      animal models have led to new insights into the pathophysiology of these
      disorders. In this review, very recent developments are discussed as they pertain
      to molecular genetic diagnosis, the understanding of pathophysiology, and
      potential novel therapeutic approaches to renal cystic diseases.

PMID- 10202625
TI  - IgA nephropathy.
AB  - Immunoglobulin A nephropathy results from the abnormal deposition of IgA
      immunoglobulin in the glomerulus, which leads to the characteristic presentation
      of painless hematuria. It is the most common glomerulonephritis worldwide.
      Originally described 30 years ago, it was thought to follow a benign course. We
      now know that IgA nephropathy leads to progressive renal destruction in about one
      third of affected patients. Alteration in glycosylation of circulating IgA may be
      an important pathophysiologic mechanism that predisposes to IgA deposition,
      although how this leads to parenchymal damage remains unclear. Hypertension, high
      grade proteinuria, and elevated serum creatinine levels are known risk factors
      for progressive renal destruction. In addition to these well-recognized risk
      factors, there appear to be genetic variants, particularly within the angiotensin
      converting enzyme gene, that portend a worse outcome.

PMID- 10202626
TI  - The idiopathic nephrotic syndrome.
AB  - The nephrotic syndrome is defined by edema, hypoalbuminemia, proteinuria, and
      hyperlipemia with elevated cholesterol and triglyceride concentrations in serum
      or plasma. It may be primary or secondary to systemic disorders. Because of its
      incidence--between 2.0 and 7.0 cases per 100,000 children per year--this disorder
      is not uncommon in a busy pediatric practice, and it forms the basis of the
      referrals evaluated by a pediatric nephrology service. Over the 2 years since
      this subject was reviewed, several articles have appeared that have provided
      insights into the clinical features, etiology, pathology, pathogenesis,
      complications, and therapy of the idiopathic primary nephrotic syndrome.
      Nevertheless, a remarkable feature of this condition remains that the fundamental
      cause and pathogenesis of the most common form of primary nephrotic syndrome,
      minimal lesion nephrotic syndrome of childhood, is largely unknown. Hence, a huge
      challenge remains for researchers in the area of pediatric nephrology.

PMID- 10202627
TI  - Pathogenesis, treatment, and therapeutic trials in hemolytic uremic syndrome.
AB  - Diarrhea-associated hemolytic uremic syndrome is one of the most common causes of
      acute renal failure in childhood. Nearly all cases are the result of an
      antecedent infection by Shiga toxin--producing strains of Escherichia coli,
      especially the O157:H7 serotype. Most cases occur after ingestion of contaminated
      meat; however, new food sources such as leaf lettuce, alfalfa sprouts, and goat's
      milk have been identified, and diarrhea-associated hemolytic uremic syndrome can
      occur after exposure to contaminated water in recreational swimming sites.
      Diarrhea-associated hemolytic uremic syndrome is a systemic disease with
      activation of a variety of inflammatory cytokines. Kidney injury may result from
      direct effects of the Shiga toxin on renal tubular epithelial cells as well as
      endothelial cells. Early diagnosis of diarrhea-associated hemolytic uremic
      syndrome may be expedited by the introduction of new techniques to rapidly detect
      toxin and microorganism in stool samples. Optimal therapy of diarrhea-associated
      hemolytic uremic syndrome includes intensive management of the renal failure and
      serious extrarenal complications that may occur during the course of disease. The
      role of antibiotics in prevention and amelioration of diarrhea-associated
      hemolytic uremic syndrome remains controversial. Experimental therapies that are
      undergoing evaluation in clinical trials include SYNSORB Pk (SYNSORB Biotech,
      Inc., Calgary, Alberta, Canada), a drug designed to bind Shiga toxin in the lumen
      of gastrointestinal tract. Immunization strategies are also being developed and
      tested. It is hoped that with continued progress in this field the incidence of
      diarrhea-associated hemolytic uremic syndrome in children will be substantially
      reduced in the coming years.

PMID- 10202628
TI  - Nonanion gap metabolic acidosis in a newborn.

PMID- 10202629
TI  - Sudden infant death syndrome, child sexual abuse, and child development.
AB  - Since the introduction of the Back to Sleep Campaigns, there has been a dramatic
      reduction in sudden infant death syndrome in this country. Steven Blatt and
      Victoria Meguid review the literature surrounding sleep position. Investigators
      have continued efforts to find other modifiable risk factors of sudden infant
      death syndrome. A prospective study of more than 33,000 neonates found a link
      between a prolonged QT electrocardiogram interval and sudden infant death
      syndrome. Also discussed are investigations seeking to explain the relationship
      between smoking and sudden infant death syndrome. Ann Botash, Florence Jean-Louis
      and Mongkae Ploy Siripornsawan review the latest thinking on genital warts and
      their relation to specific viral etiologies and child sexual abuse. Other
      symptoms and signs of sexual abuse are the focus of a number of articles that can
      help the practitioner care for these unfortunate children. Catherine Church
      reviews medication options for children diagnosed with pervasive developmental
      disorders or autism spectrum disorders. Finally, in this article, risperidone,
      fluoxetine and naltrexone are reviewed.

PMID- 10202630
TI  - Oral feeding in infants.

PMID- 10202631
TI  - [Invertors--intracellular regulators of plasma membrane function].
AB  - It has been found that the activation of protein biosynthesis in various cells
      (hepatocytes, adrenocorticocytes, thyrocytes and myocardiocytes), caused by
      different factors such as multiple hormones, regeneration, hyperfunction etc.,
      leads to the development of plasmatic membrane hyperpolarization. It has also
      been shown that during protein biosynthesis activation under genome control there
      have been synthesized the intracellular regulators of plasmatic membrane state,
      called invertors. The invertors regulate the activity of membrane enzymes and ion
      channels, as well as adapt plasma membrane state to the needs of cell. With
      increasing age, the invertors synthesis alters, and this becomes an important
      genome-membraneous mechanism of aging. An experimental lifespan prolongation
      promotes to maintain the synthesis of invertors.

PMID- 10202633
TI  - [The effect of selective serotonin administration into different portions of the
      coronary vascular bed on the retrograde (collateral) coronary blood flow in
      myocardial ischemia in dogs].
AB  - The purpose of the present investigation was to determine the action of intra
      coronary infusion of serotonin on collateral blood flow in dog heart. Intra
      coronary injection of serotonin elicited a cardiogenic hypertensive chemoreflex
      and transient but marked reductions of collateral blood flow. The cardiac and
      circulatory effects of the hypertensive cardiogenic chemoreflex and reductions of
      collateral blood flow abolished by sectioning of the cervical vagi. These data
      indicate that serotonin act on blood flow in collateral-dependent tissue of
      ischemic dog heart.

PMID- 10202632
TI  - [The nitrous oxide system under conditions of chronic cerebral dopamine
      deficiency and hypoxia].
AB  - Acute experiments were conducted on adult Wistar rats two months after unilateral
      microinjection of the 6-hydroxydopamine into the medial forebrain bundle. This
      led to a greater than 90% decrease of dopamine, fell by 70% of the content of the
      stable metabolite of nitric oxide-nitrite anion and by up to 80% of nitric oxide
      synthase activity in the lesioned neostriatum. Nitric oxide synthase activity
      fell by 30% in the heart, by 60% in the aorta, while nitrite anion decreased in
      the heart and aorta, in blood plasma and erythrocytes by 45%, 40%, 70%, 30%
      compared with controls rats, respectively. Lesioned rats also showed changes in
      the pattern of responses of the smooth muscle of the aorta predominantly to
      endothelium-dependent (acetylcholine), rather than to endothelium-independent
      (nitroprusside) vasoreactivity. The amplitude of acetylcholine-induced relaxation
      of aortic smooth muscle decreased 4-fold, the rate of this response decreased 5
      fold and the latent period increased 4-fold. Exposure of lesioned rats, controls
      rats to moderate hypoxia for 30 min resulted in a rise of nitrite anion content
      in all tissues; it increased 2-fold in erythrocytes of lesioned rats vs controls
      rats, in the lesioned and unlesioned neostriatum hypoxia restored the values to
      controls, while in the heart, aorta and plasma the levels were also increased but
      did not reach control values. Hypoxia also led to a rise of nitric oxide synthase
      activity in both lesioned rats and controls rats. However, compared to normoxia,
      the levels increased over 2 times in the lesioned neostriatum and in the heart,
      whereas in controls the increase was less that 2-fold. Hypoxia resulted in
      partial normalization of the functional deficit in endothelium-dependent dilatory
      responses of aortic smooth muscle. We conclude that the disturbances in nitric
      oxide system induced by mesostriatal dopaminergic lesions in animals may have
      relevance to Parkinson's disease. The improvement with ambient hypoxia in
      quantitative and functional aspects of the disturbances in nitric oxide system
      may also have relevance in the management of the disease.

PMID- 10202634
TI  - [The effect of membrane channel agonists and antagonists on hemodynamics and
      vascular tonus].
AB  - Compound "C" which was synthesized in Institute of Organic Chemistry NA of
      Science unite in one molecule remnant of 4-aril-1,4-dihydropyridin kernek cause
      it as calcium channel block-up property and group of molecule pinacidil which
      determine if effect as activation potassium channels. This compound cause
      essential decrease arterial pressure and total periphery resistance of vessels.
      The decrease this figures of hemodynamic connect with reducing vessels tone. This
      is proved by substantial decrease contractile activity isolated strips of aorta
      and portal vein by compound "C". The mechanism reducing tone, as demonstrate
      investigations on isolated solitary smooth muscle mesenterial arteries, cause
      with increase potassium current, hyperpolarization of cell's membrane, and with
      depresses calcium current in L-type Ca(2+) channels.

PMID- 10202635
TI  - [The role of a systemic inflammatory process in the atherogenic modification of
      lipoproteins and the development of hypercholesterolemia].
AB  - The aim of the investigation was the determination of the systemic inflammatory
      process significance as a casual factor of the atherogenic blood lipoprotein (LP)
      modification and hypercholesterolemia (HCE) development. The availability of the
      HCE and atherogenic LP in blood of the patients with chronic coronary disease was
      established to coincide with the distinct sighs of the inflammatory process such
      as monocytes activation and oxidative stress development. Under the primary
      character of the inflammation--in children with acute respiratory infectious
      diseases and in conditions of experimental rendering of acute inflammation in
      rabbits by the intravenous injection of latex microspheres or pyrogenal there was
      also determined the distinct dependence between monocytes activation, increasing
      in blood free radical processes intensity, LP atherogenic modification and HCE
      development. The dependence was confirmed by the results of the paired
      correlative analysis. The obtained data allowed to draw a conclusion that the
      systemic inflammatory process and induced by it free radicals reactions in blood
      were the independent causal factors of atherogenesis.

PMID- 10202636
TI  - [The effect of shear stress on vascular endothelium].
AB  - Effects of shear stress on intracellular Ca2+ concentration ([Ca2+]i) and
      membrane potential of intact endothelium of the rat aorta have been investigated.
      Shear stress and acethylcholine both evoked endothelium-dependent relaxation of
      the rat aorta, but in contrast to acethylcholine shear stress did not affect
      [Ca2+]i and membrane potential of the endothelium. These data do not corroborate
      the hypotheses on involvement of Ca2+ and membrane potential in reception of
      shear stress by endothelium.

PMID- 10202637
TI  - [The interrelation of neural and humoral cardiogenic influences and their action
      on the blood circulation].
AB  - The role of some endogenous bioregulators in formation of cardiogenic reflectory
      effects on circulation were investigated in acute experiments on anesthetized
      animals with using various methods (direct recording of impulse activity from
      cardiac afferent nerves, humoral isolation of the heart). Interrelations between
      development of cardiogenic depressor reactions and nitric oxide production was
      established. Systemic inhibition of NOS led to decrease in dilatation of coronary
      and peripheral vessels. At the other hand dramatic suppression of cardiogenic
      depressor reflexes followed by inhibition of prostacyclin production. The data
      support the essential role of endogenous bioactive substances in formation of
      cardiogenic reflex effects on circulation in physiological and pathological
      states. We also suggest that a mayor metabolite of arachidonic acid--prostacyclin
      -is modulator and one of humoral components of the vagus-mediated cardiogenic
      depressor reflex in physiological conditions.

PMID- 10202638
TI  - [The modulating effect of endothelial relaxing factor on the reactivity of the
      myocardium and of arterial vascular strips].
AB  - Under successive coperfusion of the arterial vascular rings and right atrial
      trabecula an examination of effects of endothelium-derived NO on reactions of
      vessel and myocardial trabecula recipient has been done. During arterial rings
      contraction a relaxing factor was released into solution. By means of chemical de
      endothelialization, NO-synthase inhibition and L-arginine the role of endothelium
      as a source of modulated substances and the role of NO as a main dilated
      substance for recipient preparations were shown. The direct effect of endothelium
      derived NO on a tension and reactivity of myocardial trabecula has been
      demonstrated.

PMID- 10202640
TI  - [Reactive hyperemia in hypertension].
AB  - This study was designed to investigate whether endothelium-dependent reactive
      hyperemia (RH) is altered in patients with hypertensive disease (HD). In 35
      mildly (HDI) patients, 38 hardly (HDII) patients, and 41 age-matched healthy
      subjects being as a control (C), forearm blood flow (FBF) was measured by means
      of impedance plethysmography before and after 30-second occlusion. Resting FBF
      was comparable in all groups while the maximal increase in FBF during RH was
      reduced in HD versus that in healthy. The difference in FBFmax between HDI and
      HDII was statistically significant showing the maximal vasodilatory reserve and
      consequently endothelial function to be dependent on the HD stage. Thus, the
      obtained data have indicated stage-dependent endothelial dysfunction in the
      patients with hypertensive disease. Designed method for evaluation of endothelial
      function by RH level may be successfully used in clinic for early and
      differential diagnostics of vascular disease.

PMID- 10202639
TI  - [The effect of L-arginine on the ultrastructure of atrial cardiomyocytes in
      experimental hypercholesterolemia].
AB  - The results of electronmicroscopic study of the right atrium in experimental
      hypercholesterolemia revealed a disturbance of ultrastructural organisation of
      both cardiomyocytes and endothelial cells of blood microvessels. Intake of L
      arginine--a precursor of synthesis of nitric oxide (NO)--with atherogenic diet
      was found to prevent to some extent the damage of ultrastructural organisation of
      cardiomyocytes and to stimulate the production of atrial granules. A significant
      number of secretory components, which differ in terms of structure and function,
      revealed in the endothelium of blood microvessels may testify to the fact that
      upon administration of L-arginine the paracrine effect of hormonal regulation is
      enhanced manifesting itself through an increase of synthesis and secretion of
      natriuretic hormone in atrial cardiomyocytes. A tissue hormonal system is
      displayed through an increase of synthesis and secretion of atrial natriuretic
      hormone in cardiomyocytes. On the other hand, a NO precursor L-arginine may
      produce a correcting effect upon the ultrastructure of endotheliocytes in
      hypercholesterolemia.

PMID- 10202641
TI  - [The central mechanisms regulating the blood circulation in hyperuricemia].
AB  - In experiments conducted on male Wistar rats for elucidation the role of central
      mechanisms in development alterations of heart electric stability was studied
      activity of 5(1)-nucleotidase and adenosine desaminase in sensomotor cortex,
      hypothalamus and hippocamp. Were shown that changes of heart function were in
      case increased adenosine content in neurons of sensomotor cortex, hypothalamus
      and hippocamp. Introduction to animals with hyperuricemia DOCA, with activate
      5(1)-nucleotidase and adenosine desaminase, was accompanied by changes of cAMP
      and cGMP content in neurons. Developing alterations of heart electric stability
      suggest the responsibility of injury adenosine metabolism in different brain
      structures of animals with hyperuricemia in alterations of central regulatory
      mechanisms of systemic blood flow.

PMID- 10202642
TI  - [Changes in the oxygen-binding properties of the blood in white rats under the
      influence of hypoxia and its pharmacological correction].
AB  - It was shown that acute (7% of oxygen in nitrogen, 30-60 min) and chronic hypoxic
      hypoxia (adaptation to the conditions of the middle mountains 2100 m above sea
      level) increased hemoglobin contents and organic phosphates--2,3-DPG and ATP in
      Wistar rats. Preliminary administration of taurine, taurile, ionole in normal and
      hypoxic conditions had no essential effect on the oxygen blood capacity where as
      the content of 2,3-DPG and glucoso-6-phosphate dehydrogenase activity increased.
      Taurin was more effective, than tauril.

PMID- 10202643
TI  - [The effect of normobaric hypoxia on the indices of the cardiorespiratory and
      immune systems in the inhabitants of radiation-contaminated regions].
AB  - The results of normobaric hypoxia therapy in patients from ecological clean
      regions of Ukraine and patients from ionizing radiation pollution regions are
      analyzed. The positive effect is obtained in both groups. It is shown that
      intermittent normobaric hypoxia normalize the state of the blood circulation,
      respiration, hemopoiesis and immunological reactivity. It is shown the normalize
      of expressing the surface markers by lymphocytes for patients from ionizing
      radiation pollution regions.

PMID- 10202644
TI  - [The effect of food products with an elevated radionuclide level on the blood and
      urine indices in rats].
AB  - Food influence, including raw meat with radionuclides (6.66 x 10(3) - 20.72 x
      10(3) Bq/kg) during 30 days, on some homeostasis values was studied in white not
      pedigree rats. Erythrocyte number decrease, leukocyte total number increase by
      twice, young cell-metamyelocyte appearance, the decrease of total protein
      quantity and of blood serum gamma-globulin fraction level, liver enzyme activity
      decrease, and liver function disturbance have been ascertained. The obtained data
      can be the grounds for the future studies in the field of prognostic criterion
      development for the evaluation of ionizing irradiation small dose effect on the
      organism.

PMID- 10202645
TI  - [The effect of the parenteral administration of alpha-ketoglutarate on the
      resistance of rats to ionizing radiation and on their cholinergic systems].
AB  - We have investigate the effect of sodium ketoglutarate intraperitoneal injection
      (20 mg/100 g body weight) made 0.5 hour before and 1, 2 and 3 hours after total X
      ray treatment (259 mKl/kg) on the survival of rats. Simultaneously we have define
      changes in cholinesterase-acetylcholine system and content of adrenaline and
      noradrenaline in liver and pancreas tissues, small intestines mucous and in
      blood. All the data were taking at 1, 2, 5, 4, 24 and 72 hours after treatment
      and sodium ketoglutarate injection. We have found that sodium ketoglutarate
      injection made 0.5 hour before the treatment results in increasing of percentage
      death rate and injection made 1 and 2 hours after treatment results in increase
      in survival of rats. The effect of alpha-ketoglutarate injection made 1 hour
      after treatment in more pronounced. It is accompanied with increase of
      cholinergic status of organism on the catecholamine deficit background, decrease
      in the cholinesterase activity and increase of acetylcholine content in tissues
      of treated organism.

PMID- 10202646
TI  - [Convergence studies of hypothalamic neurons].
AB  - In this study has been reveibed the peculiarities of convergence of afferent
      cortical inputs to the hypothalamic neurons. Single and the serial stimulation of
      phylogenetically distinct cortical areas (proreal cortex (field 8), cingular
      cortex (field 24), pyriform lobule (periamygdala cortex), and hippocampus (CA3)
      were used. We have established two main focuses of expressed convergence of
      signals from the above mentioned cortical areas. First of them was located in the
      lateral hypothalamus nucleus, second--in the centromedial hypothalamus nucleus.
      Single cortical stimulation was found to excite majority of hypothalamus neurons.
      Expressed prevalence of inhibitory responses over excitatory ones were found in
      case of serial stimulation application. This functional organisation of the
      hypothalamic nucleus allow to propose tonic character of the cortical influences
      due to serial stimulation and the eventual character of these influences due to
      single stimulation.

PMID- 10202647
TI  - Sequencing of cognitive-behavioral treatments for bulimia nervosa.
AB  - OBJECTIVE: This study investigated the efficacy of a stepped-care trial of brief
      group psychoeducation (PE) followed by individual cognitive-behavioral therapy
      (CBT) in the treatment of bulimia nervosa. METHOD: Fifty-six subjects first
      completed PE and were then randomly assigned to either a 16-week trial of CBT (PE
      + CBT) or to no further treatment follow-up (PE-alone). RESULTS: Compared to PE
      alone, PE + CBT produced significantly greater reductions in the specific eating
      symptoms of binging and purging and significantly higher remission rates that
      were maintained over a 16-week follow-up. However, there were no differential
      treatment effects on measures of nonspecific psychopathology. Among PE + CBT
      subjects, remission in specific eating symptoms was associated with greatest
      improvements in non-specific psychopathology. The outcome of nonremitted PE + CBT
      subjects and PE-alone subjects was no different at posttreatment or follow-up.
      DISCUSSION: These results provide limited support for offering individual CBT to
      subjects once they have completed an initial trial of group PE.

PMID- 10202648
TI  - Risk factors for the emergence of childhood eating disturbances: a five-year
      prospective study.
AB  - OBJECTIVE: Research suggests that eating problems are often present by
      preadolescence, yet little is known about the age of emergence of these early
      eating disturbances or risk factors for these behaviors. Thus, we investigated
      the timing of onset of disturbed eating during childhood and the predictors of
      these behaviors. METHOD: These aims were addressed by following a sample of
      children and their parents (N = 216) for the first 5 years of the children's
      lives. RESULTS: Data suggested that the risk for emergence of inhibited eating,
      secretive eating, overeating, and vomiting increased annually through age 5.
      Maternal body dissatisfaction, internalization of the thin-ideal, dieting,
      bulimic symptoms, and maternal and paternal body mass prospectively predicted the
      emergence of childhood eating disturbances. Infant feeding behavior and body mass
      during the first month of life also predicted the emergence of these behaviors.
      DISCUSSION: Results suggest that eating disturbances emerge during childhood and
      may be a function of certain parental and child characteristics.

PMID- 10202649
TI  - Emotion-induced eating and sucrose intake in children: the NHLBI Growth and
      Health Study.
AB  - OBJECTIVE: Emotion-induced eating has been implicated as a risk factor for the
      development of obesity, yet no research has been done on emotion-induced eating
      in children. The National Heart, Lung, and Blood Institute Growth and Health
      Study (NGHS), a multicenter collaborative study of risk factors for obesity,
      developed an instrument for measuring emotion-induced eating in children and
      tested hypotheses regarding the association of emotion-induced eating with food
      intake and adiposity in preadolescent children. METHOD: Subjects were 1,213 black
      girls and 1,166 white girls who were 9 and 10 at study entry. Baseline data were
      utilized in this report. Girls were assessed by trained female health examiners
      who recorded height, weight, and indices of sexual maturation. Girls kept a 3-day
      food diary. Dietary data were coded and analyzed for total caloric and macro
      nutrient intake. A measure of emotion-induced eating was derived from seven
      questions about eating in response to emotions (Cronbach's alpha = .78). RESULTS:
      Black girls had significantly higher emotion-induced eating scores than white
      girls (10.8 vs. 9.7, p < .0001). For white girls, but not for black girls,
      emotion-induced eating was associated with increased intake of sucrose. In both
      races, a modest inverse association was found between body mass index and emotion
      induced eating. DISCUSSION: Prospective studies are needed to explore further the
      role of emotion-induced eating and food intake and the role of emotion-induced
      eating in the development of obesity.

PMID- 10202650
TI  - Psychiatric comorbidity of eating disorders in men: a national study of
      hospitalized veterans.
AB  - OBJECTIVE: This study examined eating disorders and their psychiatric comorbidity
      in a national sample of hospitalized male veterans. METHOD: Review of discharge
      summaries for 466,590 male patients from Veterans Affairs medical centers for
      fiscal year 1996 resulted in the identification of 98 men with a current ICD-9-CM
      diagnosis of an eating disorder. For the comorbidity analyses, eating disorder
      cases were matched with controls drawn randomly from the pool of male patients
      without an eating disorder, using age and race as matching variables. RESULTS:
      There was a high rate of comorbid substance use and mood disorder for men with
      anorexia nervosa (AN), bulimia nervosa (BN), and eating disorder not otherwise
      specified (EDNOS). Men with AN were also at high risk for comorbid
      schizophrenia/psychotic disorder, men with BN were at risk for comorbid
      personality disorder, and men with EDNOS were at special risk for comorbid
      organic mental disorder and schizophrenia/psychotic disorder. DISCUSSION: For
      each eating disorder, there was a distinct pattern of psychiatric comorbidity
      that deserves further study.

PMID- 10202651
TI  - Eating disorders in a national sample of hospitalized female and male veterans:
      detection rates and psychiatric comorbidity.
AB  - OBJECTIVE: Using a national sample of hospitalized female and male veterans, this
      study examined the point prevalence of detected cases of eating disorders and
      explored psychiatric comorbidity in cases with an eating disorder. METHODS:
      Prevalence rates were determined by reviewing the discharge diagnoses of 24,041
      women and 466,590 men hospitalized in Veteran Affairs medical centers during
      fiscal year 1996. Comorbidity was examined by individually matching eating
      disorder cases (N = 161) with patients without an eating disorder, using sex,
      race, and age as matching variables. RESULTS: On the basis of routine clinical
      diagnosis, 0.30% of the female veterans and 0.02% of the male veterans were
      diagnosed with a current ICD-9-CM eating disorder. Women with eating disorders
      had significantly elevated rates of comorbid substance, mood, anxiety
      (particularly posttraumatic stress disorder [PTSD]), adjustment, and personality
      (particularly borderline personality disorder [BPD]) disorders. Men with eating
      disorders were found to have high rates of comorbid organic mental,
      schizophrenic/psychotic, substance, and mood disorder. CONCLUSIONS: Our study
      illustrates the value of administrative data sets for the investigation of
      uncommon diseases.

PMID- 10202652
TI  - More males seek treatment for eating disorders.
AB  - OBJECTIVE: This study compares males and females with DSM-IV-defined eating
      disorders who were admitted to the inpatient eating disorders service at The New
      York Hospital, Cornell between 1984 and 1987. METHODS: During this period, 51
      males and 693 females presented for their first admission. Demographic
      information, questionnaires, and SCID interviews were used to compare the male
      and female samples. RESULTS: Males were significantly more likely than females to
      have a later onset of their eating disorder (20.56 vs. 17.15 years), and to be
      involved in an occupation or sport in which weight control influences
      performance. There were no significant gender differences in other
      characteristics or comorbid diagnoses. Males constituted an increasing percentage
      of total admissions between 1984 and 1997 (r = .692, p = .009). DISCUSSION: The
      similarities of core eating disorder psychopathology and comorbid illness in male
      and female patients encourage the continued use of similar detection and
      treatment strategies with both groups.

PMID- 10202653
TI  - The role of ethnicity and parental bonding in the eating and weight concerns of
      Asian-American and Caucasian college women.
AB  - OBJECTIVES: The purpose of this research was to explore the associations among
      ethnicity, parental bonding, acculturation, and eating disturbance in Asian
      American and Caucasian weight-concerned college women. METHODS: Twenty-five Asian
      American and 26 Caucasian weight-concerned women were administered the Eating
      Disorder Examination interview, the Parental Bonding Instrument, and three
      subscales of the Eating Disorder Inventory. Asian-American subjects also filled
      out the Suinn-Lew Asian Self-Identity Acculturation Scale questionnaire. RESULTS:
      Contrary to hypotheses, weight-concerned Asian-American women reported more
      dissatisfaction with body shape than did Caucasian women. Moreover, in the Asian
      American group, acculturation was not associated with level of eating
      disturbance. In both groups, perceptions of low maternal caring were associated
      with higher levels of eating problems. In regression analyses, maternal care
      emerged as a better predictor of eating disturbance than did ethnicity.
      DISCUSSION: Results suggest that quality of parent-child relations, particularly
      the mother-daughter relationship, may be important in the etiology of eating
      problems, irrespective of ethnicity. Longitudinal investigations will be required
      to test causal relations.

PMID- 10202654
TI  - Dieting and the family context of eating in young adolescent children.
AB  - OBJECTIVES: The potential for undernutrition and links with eating disorders make
      early dieting an issue of concern. The aim of this research was to examine the
      eating patterns, social circumstances of eating, and parental use of food in
      young adolescent dieters. METHODS: Four hundred and two 12-year-old children (200
      girls, 202 boys) completed assessments of dieting, eating patterns, food-related
      nurturance, and parental control of eating, together with body weight, height,
      and self-perception. RESULTS: Current dieting (20% girls, 8% boys) was strongly
      associated with fasting and dietary restraint. Highly restrained children ate
      fewer meals and snacks and reported significantly greater parental control of
      their eating. However, they did not differ in the social context of eating or in
      food-related nurturance. Dieting status was a stronger determinant than body
      weight of all these differences. CONCLUSIONS: These findings suggest that 12-year
      old dieters are quite serious in their nutritional intentions. They also confirm
      an active role for parents in their children's dieting. Both children and their
      parents are in need of age and gender-specific advice concerning eating and
      weight.

PMID- 10202655
TI  - Success and failure in the measurement of restraint: notes and data.
AB  - OBJECTIVE: The clarification of the present confusion about the confounding of
      success and failure in the measurement of restrained eating. METHOD: Close
      inspection of results regarding the Restraint Scale (RS) and the restraint scales
      of homogeneous measures of restrained eating, for example, the restraint scales
      of the Three-Factor Eating Questionnaire (TFEQ) and the Dutch Eating Behaviour
      Questionnaire (DEBQ). RESULTS: Various studies have led to the distinction of two
      different types of confounding of success and failure in the measurement of
      restrained eating. The first confounding is associated with the RS and the
      inability of its scores to differentiate between inhibition and disinhibition of
      restraint in one person, as a result of variance across time within one person in
      food intake and binging. The second type of confounding applies to the
      homogeneous measures of restrained eating, for example, the restraint scales of
      the TFEQ and DEBQ. Here the confounding is associated with the inability of their
      restraint scores to differentiate between dieters with low versus high
      susceptibility toward failure of restraint, as a result of variance across
      persons in food intake and binging. DISCUSSION: In contrast to the first
      confounding, the confounding of successful and unsuccessful dieters in subjects
      with high restraint scores can be easily unconfounded, by using a two-factorial
      classification including both scores on "pure" measures of restraint and scales
      for tendency toward overeating. For future research, the distinction between
      successful and unsuccessful dieters is an important first step in clarifying why
      some dieters do overeat under certain conditions.

PMID- 10202656
TI  - Body size categorization in anorexia nervosa using a morphing instrument.
AB  - OBJECTIVE: To test the feasibility of the technique of "morphing" for body image
      assessment purposes and to investigate whether females with anorexia nervosa (AN)
      categorize other female's body sizes similarly to controls. METHOD: A morphing
      movie showing the transformation of a thin woman into an obese woman was
      presented. Females with AN and thin controls selected the sizes corresponding to
      the transitions between the body size categories thin, normal, fat, and obese.
      They were instructed to look at the woman in the movie as themselves (Self)
      versus someone else (Other). RESULTS: The AN group chose significantly lower
      transitions associated with the categories thin, normal, fat, and obese under the
      Self instruction than controls. Similarly, they selected lower settings for all
      but the obese category when looking at the body as someone else's. It was
      concluded that females with AN display a harsher judgment not only of their own
      body size and shape, but also of that of another woman, than women without an
      eating disorder. DISCUSSION: The morphing instrument was found to be sufficiently
      realistic, detailed, and sensitive for its intended purposes.

PMID- 10202657
TI  - Eating disorders in adolescents and young women with spina bifida.
AB  - This is the first report of the association of spina bifida and eating disorders.
      Five patients were diagnosed rather late in the course of their illness. They all
      had been overweight premorbidly and had been urged to lose weight for years in
      order to improve their mobility. As they dieted, they experienced their weight
      loss as a source of power that could somehow compensate for their losses and
      neurologic limitations. They responded to a multidisciplinary intervention.
      Clinicians taking care of patients with spina bifida need to be cognizant that
      they may be at risk of developing an eating disorder. Such awareness should
      influence the quality of nutritional counseling (prevention aspect) and the
      clinical assessment of sudden weight loss (early intervention).

PMID- 10202658
TI  - Severe anorexia nervosa associated with osteoporotic-linked femural neck fracture
      and pulmonary tuberculosis: a case report.
AB  - We report a case study of a 38-year-old woman who had been suffering from
      anorexia nervosa (AN) since the age of 26. Before admittance to our clinic, she
      weighed 23.8 kg (at a height of 164 cm, 8.8 body mass index [BMI]) but still
      carried out strenuous physical activities. After good psychotherapeutic response
      and weight gain (34.4 kg), she accidentally fell and broke her femoral neck
      favored as it was by osteoporosis. The X-ray taken before dynamic hip screw
      implantation coincidentally showed signs of pulmonary tuberculosis (TB), which
      could then be proven by computed tomography (CT) scans and cultures from a
      bronchoscopy. Other than lack of appetite and loss of weight, which we attributed
      to AN, there were no other clinical or biochemical indicators which could have
      pointed to an earlier TB diagnosis. As a result, the need for screening
      procedures is discussed. The manifestation of TB during the first weight gain
      after 12 years of severe malnutrition, during which there were no serious
      infections, seems to endorse former observations that AN patients appear to be
      "resistant" to some extent against infectious diseases, a "protection" which may
      be lost with convalescence and weight gain.

PMID- 10202659
TI  - Lower dosages of phentermine-fenfluramine given in the afternoon: five cases with
      significant weight loss.
AB  - Phentermine and fenfluramine are widely used in the treatment of obesity. Despite
      the fact that primary pulmonary hypertension and mitral valve insufficiency have
      been associated with fenfluramine use, many of these patients need medication to
      achieve weight loss. Small degrees of weight loss have been shown to
      significantly improve obesity-related medical conditions such as hypertension,
      hypercholesterolemia, and noninsulin-dependent diabetes mellitus. Current
      practice is to give phentermine and fenfluramine in the morning and afternoon.
      Doses for phentermine have ranged from 15 to 37.5 mg and for fenfluramine from 20
      to 120 mg per day. We report five cases of severely obese women with medical
      complications who were treated with phentermine 8 mg twice per day (at 1:00 p.m.
      and 4:00 p.m.) and fenfluramine 20 mg per day (at 4:00 p.m.). Because many obese
      patients skip breakfast and eat more in the afternoon and evening, medication was
      dosed in order to cover these high-risk eating periods. Overall, these patients
      lost a mean of 22.4% of their initial weight (range 18.6% to 32.8%) over an
      average of 8.4 months (range 3.5 to 16 months). These cases suggest that short
      term weight loss can be achieved with a low dose of fenfluramine when both
      medications are given in the afternoon to better target the eating patterns of
      obese subjects.

PMID- 10202660
TI  - Useful services for families: research findings and directions.
AB  - A major tenet of gerontological practice and policy has been that community-based
      services relieve stress on family caregivers and delay or prevent
      institutionalization of frail elders. Evidence for benefits of community-based
      services is examined from four perspectives: (1) relief for family caregivers;
      (2) benefits to older clients; (3) delay or prevention of institutionalization;
      and (4) cost-effectiveness or cost-benefits of a service. Studies are grouped
      according to the type of service (in-home respite, adult day care, overnight
      respite, case management and multicomponent programs) and type of clients
      (dementia only or mixed). There are surprisingly few empirical studies overall
      and the reported benefits typically are modest. Methodological problems as well
      as providing relatively small amounts of service may have accounted for these
      findings. Studies in which clients and/or their families received adequate
      amounts of help showed more consistently positive outcomes. There is little
      evidence, however, to suggest that community services delay placement. More needs
      to be done to examine the benefits of innovative programs, and particularly to
      incorporate the dementia patient's perspective into these evaluations.

PMID- 10202661
TI  - Formal and informal support: the great divide.
AB  - As we approach the next century, it is clear that neither formal services nor
      informal family caregivers can meet the needs of a growing population. It is
      therefore pertinent to reconceptualize the linkages between formal and informal
      care and move towards an integrative model. This paper explores several models of
      such an interface that exist in the literature and proposes that many of these
      overlap. Various predictors of formal service use are also explored, with an
      emphasis on the outcomes of both the informal caregiver and the care recipient.
      Implications for future research include further exploring and understanding the
      link between formal and informal support and the need to increase receipt of
      formal care among family caregivers.

PMID- 10202662
TI  - Enabling and empowering certified nursing assistants for quality dementia care.
AB  - Currently, 1.2 million full-time equivalent employees (FTEs) care for more than
      1.5 million residents in nursing homes where 75% of residents have dementia. By
      the year 2010, the number of residents in these institutions may double.
      Registered nurses (RNs) make up less than 7% of a home's total FTEs. In contrast,
      certified nursing assistants (CNAs) account for more than 40% of total FTEs.
      Thus, CNAs serve as the primary caregivers in nursing homes. Typically, CNAs have
      a high school education or less, and receive little more than minimum wage. Their
      extensive contact with residents has a tremendous impact on quality of life, but
      significant barriers limit their caregiving effectiveness. These barriers include
      poor pay, minimal long-term benefits, and insufficient training, recognition and
      support for their physically and emotionally labor-intensive care. This paper
      addresses the issues of training CNAs for dementia care by suggesting an
      organizational framework within which to view dementia training; providing an
      overview of barriers to empowering CNAs to provide quality care to dementia
      residents; reviewing research that has addressed a specific barrier; making
      recommendations for future research; and suggesting research approaches to
      address these recommendations.

PMID- 10202663
TI  - Effective behavioral interventions for decreasing dementia-related challenging
      behavior in nursing homes.
AB  - This paper provides a selective review of behavioral intervention research aimed
      at successfully decreasing dementia-related challenging behaviors in nursing
      homes. The authors include separate discussions of behavioral excesses
      (disruptive vocalization, wandering, physical and verbal aggression) and deficits
      (excess dependency, therapeutic activities, social interaction/communication).
      Descriptions of interventions used to address each behavior problem are followed
      by methodological evaluations of the research. Discussions are augmented by
      inclusion of the authors' ongoing intervention research. The paper concludes with
      a description of a comprehensive program for teaching behavior management skills
      to nurse aides and a motivational system for maintaining the performance of these
      skills over the long term.

PMID- 10202664
TI  - Current awareness in geriatric psychiatry.

PMID- 10202665
TI  - CD44 is a marker of endocervical neoplasia.
AB  - The expression of CD44s, CD44v4, CD44v5, CD44v7-8, and CD44v10 was investigated
      immunohistochemically in a variety of neoplastic cervical lesions. Normal
      endocervical columnar cells exhibited no reactivity for any of the antibodies,
      whereas the subcolumnar reserve cells were strongly positive for CD44s, CD44v5,
      and CD44v7-8. In some cases, positive cells were identified in the stroma
      surrounding the endocervical glands and adjacent to reserve cells. Cervical
      glandular intraepithelial neoplasia and adenocarcinoma showed consistent
      immunoreactivity for CD44v5. There was no significant change in CD44
      immunoreactivity in squamous cell carcinoma compared with normal epithelia and
      cervical intraepithelial neoplasia. These findings lend support to the origin of
      carcinoma of the cervix from a common progenitor reserve cell and suggest the
      origin of reserve cells from the stroma. CD44v5 may be useful as a diagnostic
      marker of endocervical neoplasia and could provide a target for therapeutic
      approaches directed against specific epitopes.

PMID- 10202666
TI  - Abnormal expression of sex steroid receptors and cell cycle-related molecules in
      adenocarcinoma in situ of the uterine cervix.
AB  - It was recently reported that cervical adenocarcinoma showed an abnormal
      expression of estrogen receptor (ER) and cell cycle-related molecules (cyclin E,
      p53, p16, p21, and p27). To investigate whether similar alterations exist in
      glandular intraepithelial lesions, the expression of ER, progesterone receptor
      (PR), Ki-67, and the above cell cycle-related molecules was examined in 15 cases
      of glandular dysplasia (GD) and 10 cases of adenocarcinoma in situ (AIS), using
      the immunohistochemical technique. An expression of ER and PR was often decreased
      or missing in GD and, especially, in AIS. The Ki-67 labeling index was
      significantly higher in AIS than in GD or normal glandular cells. In GD,
      expression of all the cell cycle-related molecules was not recognized (except for
      a few p27-positive cases), a situation comparable to normal glands. In contrast,
      an abnormal expression of all the cell cycle-related molecules examined was
      demonstrated in AIS. There was a significant positive correlation, in terms of
      the extent of staining, between cyclin E and p21 in AIS. These results suggest
      that an altered expression of these molecules occurs in AIS as it does in
      invasive adenocarcinoma, and provide additional evidence supporting AIS as a
      precursor of cervical adenocarcinoma.

PMID- 10202667
TI  - Artifact in cervical LLETZ specimens: correlation with follow-up.
AB  - The effect of cautery artifact on the ability to accurately diagnose dysplasia
      and predict abnormal follow-up in large loop excision specimens of the
      transformation zone (LLETZ) has not been adequately addressed in the pathology
      literature. One hundred consecutive conization specimens with cytologic and/or
      histologic follow-up were studied. Indications for the procedure were high-grade
      squamous intraepithelial lesion (on Pap smear and/or biopsy) in 64 cases, low
      grade squamous intraepithelial lesion in 28, atypical squamous cells of unknown
      significance (ASCUS) in 3, atypical glandular cells of unknown significance in 2,
      adenocarcinoma in situ, squamous carcinoma in situ, and invasive squamous
      carcinoma in 1 each. Twenty-four specimens were cold-knife conizations (CKCs) and
      76 LLETZs. All LLETZs had at least 1+ artifact, and in 46 cases (61%) it
      interfered with at least one aspect of evaluation. In 21 cases (28%), 1+ artifact
      interfered only with margin assessment. In 25 cases (33%), there was 2+ or 3+
      artifact precluding not only margin assessment, but also diagnosis and grading of
      dysplasia. Of the 43 LLETZs received in more than one piece, 33 (77%) had
      interfering artifact, and in 21 (49%) it was 2+ or 3+, at least focally
      interfering with diagnosis and grading. In contrast, of 33 LLETZs received in a
      single piece, only 13 (39%) had interfering artifact, which was 2+ or 3+ in 4
      (12%), (p < 0.05). Positive follow-up (including ASCUS, favor dysplasia, and
      ASCUS, not otherwise specified) was found in 6 of 7 CKCs with positive margins
      (86%), 10 of 16 LLETZs with positive margins (63%), and 4 of 7 LLETZs with
      unassessable margins (57%). In cases with negative cone margins, positive follow
      up was found in 2 of 17 CKCs (12%), and 18 of 53 LLETZs (34%), p < 0.05; a higher
      frequency of interfering artifact (p < 0.05) was seen in these cases. LLETZ
      margin status and postprocedure endocervical curettage (ECC) specimens were not
      good predictors of residual disease, unlike margin status in CKC. Post-CKC ECC
      was a better predictor of subsequent abnormal follow-up than post-LLETZ ECC (p <
      0.05). The presence of interfering artifact was only rarely mentioned in the
      original pathology report. In conclusion, the status of margins is a better
      predictor of abnormal follow-up in CKC than in LLETZ specimens. Fragmentation of
      the specimen is an additional factor, compounding the inevitable artifact.
      Postprocedure ECC is not a useful indicator of residual dysplasia. The
      pathologist should not hesitate to comment on specimen adequacy in surgical
      pathology reports.

PMID- 10202668
TI  - MIB-1 expression is useful in distinguishing dysplasia from atrophy in elderly
      women.
AB  - Both atrophic and dysplastic cervical squamous epithelia show lack of maturation,
      nuclear crowding, and increased nuclear/cytoplasmic ratio. Because of these
      similarities, distinguishing dysplasia from atrophy in cervical biopsies from
      elderly patients is often problematic. Because dysplasia shows increased
      proliferation and atrophy has decreased proliferation, the possible utility of
      MIB-1 in distinguishing dysplasia from atrophy was evaluated. One or more of the
      following criteria were present in all nine cases with dysplasia and in none of
      the 17 cases with atrophy: MIB-1 expression in > 20% of cells in the basal one
      third of the epithelium, > 5% of cells in the middle one-third of the epithelium,
      and > 1% of cells in the upper one-third of the epithelium. MIB-1 immunostaining
      is useful in distinguishing dysplasia from atrophy.

PMID- 10202669
TI  - Immunophenotype of transitional metaplasia of the uterine cervix.
AB  - Transitional, glandular, and squamous epithelia show distinctive patterns of
      expression of cytokeratins 13, 17, 18, and 20. Furthermore, some markers, such as
      cytokeratin (CK) 20 and the asymmetric unit membrane, are related to terminal
      urothelial differentiation, their expression limited to superficial and
      occasional intermediate cells. In this study, seven cases fulfilling the
      morphologic criteria of transitional metaplasia of the uterine cervix were
      investigated with these markers to determine whether there was evidence of true
      urothelial-type differentiation in these lesions. Results were consistent and
      showed clear differences between the squamous, glandular, and metaplastic
      transitional areas of the cervix. In particular, the expression of CK13, CK17,
      and CK18 in the metaplastic areas was identical to the pattern observed in normal
      urothelium. However, full urothelial differentiation was not observed, as CK20
      and asymmetric unit membrane were never expressed in the transitional metaplasia.
      Based on these findings, the term of immature transitional metaplasia would be a
      more accurate description of this entity.

PMID- 10202670
TI  - Tamoxifen and the endometrium: review of 102 cases and comparison with HRT
      related and non-HRT-related endometrial pathology.
AB  - Tamoxifen, a synthetic anti-estrogen that paradoxically acts as a partial
      estrogen agonist on the endometrium, is associated with an increased frequency of
      proliferative endometrial lesions, including hyperplasias, neoplasms, and polyps.
      Tamoxifen-related polyps are characteristically multiple and fibrotic. A variety
      of metaplasias and periglandular stromal condensation may be seen. Relatively few
      articles have focused on the descriptive morphology of the full range of
      tamoxifen-associated lesions. The present study further defines the histologic
      features in both endometrial polyps and nonpolyp endometrium. One hundred and two
      specimens (including 50 polyps) were reviewed using hormone replacement therapy
      related endometrial specimens and conventional polyps as the control groups. The
      most characteristic findings of tamoxifen-associated lesions included polarized
      glands along the long axis of polyps (40%), a cambium layer (72%), frequent and
      diverse metaplasias, staghorn glands (36%), myxoid degeneration (12%), and small
      glands (36%). Similar morphologic features were identified in the hormone
      replacement therapy and control groups but to a variable, lesser extent. Overall,
      the tamoxifen group consisted of 18 cases of hyperplasia (11 complex, 7 simple)
      and one case each of adenofibroma, adenosarcoma, endometrial stromal sarcoma, and
      leiomyosarcoma. Although none of the features is diagnostic, the presence of
      diverse metaplasias, polarized glands, staghorn glands, and a cambium layer
      strongly suggest tamoxifen exposure especially if a number of these features are
      present concurrently within the same material.

PMID- 10202671
TI  - HER-2/neu amplification and overexpression in endometrial carcinoma.
AB  - HER-2/neu is a proto-oncogene associated with poor prognosis in women with breast
      and ovarian carcinoma. The significance of HER-2/neu in endometrial carcinoma is
      less clearly established. The authors compared HER-2/neu gene amplification using
      fluorescence in situ hybridization and protein overexpression using
      immunohistochemistry with survival in patients with endometrial carcinoma.
      Fluorescence in situ hybridization and immunohistochemical staining were
      performed on 72 formalin-fixed, paraffin-embedded endometrial carcinoma
      specimens. Vysis combination HER-2/neu and centromere 17 probe mixture was
      applied to isolated tumor cell nuclei. A minimum of 200 nuclei were scored for
      each specimen using standard signal enumeration criteria. A specimen was
      considered amplified with 5% or greater amplified nuclei. Tissue sections were
      immunostained with polyclonal antibody against p185erb-2 transmembrane
      glycoprotein. Immunohistochemical reactivity was scored on a three-tiered scale.
      HER-2/neu gene amplification and protein overexpression were detected in 15 of 72
      (21%) and 12 of 72 (17%) of the specimens, respectively, with 2 cases of normal
      copy overexpression and 5 cases of amplification without overexpression. Both
      amplification and overexpression were associated with higher grade tumors.
      Amplification was associated with clear cell and serous subtypes (p = 0.002), and
      overexpression with only clear cell type (p = 0.006). Using the proportional
      hazards model of survival, amplification was found to have significant negative
      predictive value beyond stage, grade, and cell type (p = 0.002). HER-2/neu gene
      amplification as detected by fluorescence in situ hybridization in archival
      material has significant prognostic value.

PMID- 10202672
TI  - Immunohistochemical localization of inhibin-alpha in the placenta and gestational
      trophoblastic lesions.
AB  - The immunohistochemical distribution of inhibin-alpha in formalin-fixed, paraffin
      embedded tissues was evaluated in placentas (2 to 40 weeks of gestation),
      implantation sites, and a variety of trophoblastic lesions. In the first
      trimester placenta, inhibin-alpha was strongly and diffusely expressed in
      syncytiotrophoblast. Implantation site intermediate trophoblast in normal and
      exaggerated placental sites was either negative or only weakly and focally
      positive for inhibin-alpha. With increasing gestational age, the staining
      intensity and distribution of inhibin-alpha decreased in syncytiotrophoblast but
      increased in the implantation site intermediate trophoblast. Chorionic-type
      intermediate trophoblast, present in the chorion laeve of the term placenta, was
      weakly but diffusely positive for inhibin-alpha. Cytotrophoblast remained
      negative for inhibin-alpha throughout gestation. In trophoblastic lesions,
      inhibin-alpha immunoreactivity was detected in all 17 hydatidiform moles (7
      complete and 10 partial), 32 placental site nodules, 23 placental site
      trophoblastic tumors, 15 epithelioid trophoblastic tumors, and 16
      choriocarcinomas. Inhibin-alpha immunoreactivity was confined to the
      syncytiotrophoblast in hydatidiform moles and choriocarcinoma. As with the normal
      placenta, inhibin-alpha was not detected in cytotrophoblast. To evaluate the
      utility of inhibin-alpha in the differential diagnosis of gestational
      trophoblastic lesions, we tested 32 squamous cell carcinoma of the cervix, 11 low
      grade endometrial stromal sarcomas, 12 endometrial (7 well differentiated and 5
      moderately differentiated) carcinomas, 7 epithelioid leiomyomas, and 10
      leiomyosarcomas for the expression of inhibin-alpha. None of these lesions was
      positive. These data indicate that inhibin-alpha is expressed by all populations
      of trophoblast except cytotrophoblast and in all gestational trophoblastic
      lesions. Accordingly, immunohistochemical detection of inhibin-alpha is useful in
      the differential diagnosis of gestational trophoblastic lesions.

PMID- 10202673
TI  - Histopathologic features of ovaries at increased risk for carcinoma. A case
      control analysis.
AB  - In this study, the pathogenesis of ovarian carcinoma was investigated by
      performing a masked histopathologic comparison of benign ovaries removed from 61
      women predicted to be at increased risk for developing carcinoma (cases) with
      ovaries removed from 121 women without known predisposing conditions (controls).
      The cases included 26 women who had a unilateral invasive carcinoma and 35 women
      undergoing prophylactic oophorectomy for a family history of ovarian cancer. As
      predicted by previously developed models, epithelial inclusion cysts were
      identified more frequently with advancing age in both cases and controls.
      However, the mean and maximum number of cysts per slide in a woman were not
      increased among cases. Surface epithelial "atypia," a designation based on a
      composite impression of multiple features, was found in 13% of cases compared
      with 3% of controls (relative risk 7.1; 95% confidence interval, 1.9 to 26.1),
      but this result was based on small numbers. None of the other histologic features
      examined was found more often in cases following age-adjustment. Reexamination of
      sections with well-preserved surface epithelium or inclusion cysts under oil
      immersion demonstrated several differences in the detection of specific features
      between cases and controls and increased detection of "atypia" among cases, but
      none of these findings reached statistical significance. It is concluded that
      there may be subtle differences in the surface epithelium of ovaries predisposed
      to developing cancer as compared with controls, but these changes are difficult
      to identify reliably with light microscopy. Future etiologic studies should
      attempt to optimize specific handling and include molecular studies and
      epidemiologic analyses.

PMID- 10202674
TI  - Microsatellite analysis in serous tumors of the ovary.
AB  - Thirty-four serous ovarian neoplasms were analyzed for microsatellite instability
      (MIN) and loss of heterozygosity (LOH) at 20 chromosomal loci of eight different
      chromosomes, including the map positions of the six known mismatch repair genes.
      Twelve of the 20 (60%) serous ovarian tumors of low malignant potential (LMP) and
      13 of 15 (87%) samples of serous ovarian carcinomas, taken from 14 patients,
      showed LOH at one or more of the analyzed microsatellite loci. In serous
      carcinomas, LOH of the dinucleotide repeat D7S521 was most frequent. Six of 20
      (30%) LMP tumors were also affected by MIN at more than one locus, whereas in the
      carcinomas MIN was found only sporadically (p < 0.025). No correlation between
      increased occurrence of MIN and LOH at the chromosomal loci of the known mismatch
      repair genes were discovered for these LMP tumors. Although our observation
      regarding LOH frequency in serous LMP tumors and serous carcinomas is compatible
      with the hypothesis that serous LMP tumors might represent precursor lesions of
      invasive carcinomas, the results concerning the occurrence of MIN suggest that
      the mechanisms of tumorigenesis of some tumors of LMP are distinct from those in
      invasive serous carcinomas.

PMID- 10202675
TI  - Relaxin-like factor (RLF): a new specific marker for Leydig cells in the ovary.
AB  - Relaxin-like factor (RLF), also known as the Leydig cell insulin-like factor (Ley
      I-L), is a novel member of the insulin-IGF-relaxin family of hormones and growth
      factors that has recently been shown to be strongly expressed in testicular
      Leydig cells. Expression of the RLF peptide in the human ovary and in ovarian
      tumors has not been studied. In the present study, the expression of the RLF
      peptide in the human ovary was investigated by immunohistochemistry using a
      specific antibody raised against human RLF. By this method, RLF was found to be
      expressed in hilus (Leydig) cells and theca interna cells but absent in granulosa
      cells, ovarian stromal cells, and surface epithelium. RLF expression was also
      observed in the corpus luteum, although at a lower level than in theca cells.
      Thirty-seven sex cord-stromal tumors and five cases of hilar Leydig cell
      hyperplasia were also investigated for RLF expression. RLF was found to be
      strongly expressed in hilar Leydig cell hyperplasia and sex cord-stromal tumors
      with a component of Leydig or luteinized cells. Of the analyzed theca cell
      tumors, two displayed a diffuse staining pattern. As expected, RLF was not
      expressed in granulosa cell tumors. In conclusion, RLF appears to be a useful
      marker for Leydig cells in the human ovary and may be a diagnostic supplement in
      hyperplasias and tumors derived therefrom.

PMID- 10202676
TI  - Vulvar porokeratosis: case report and review of the literature.
AB  - We report the first case of vulvar porokeratosis that occurred in a 39-year-old
      woman with a 30-year history of vulvar pruritus and disfiguring vulvar lesions.
      Ultrasonic surgical aspiration resulted in resolution of her pruritus and
      excellent cosmesis. Light microscopy revealed characteristic cornoid lamellae and
      electron microscopy confirmed the diagnosis of vulvar porokeratosis.

PMID- 10202677
TI  - Virilizing ovarian dermoid cyst with peripheral steroid cells. A case study with
      immunohistochemical study of steroidogenesis.
AB  - A case of virilizing ovarian dermoid cyst with peripheral steroid cells and
      virilization is reported in a 62-year-old woman. The level of testosterone
      dropped to normal after oophorectomy. The cyst wall was bordered by a
      discontinuous band of steroid cells focally accompanied by smooth muscle cells.
      Immunohistochemically, the steroid cells were enzymatically active and displayed
      a profile similar to the internal theca cells of ovarian follicles. These steroid
      cells were most probably modified stromal cells associated with smooth muscle
      metaplasia of the ovarian stroma.

PMID- 10202678
TI  - Stromal Leydig cell tumor of the ovary. Case report and literature review.
AB  - The stromal Leydig cell tumor is a very rare benign tumor originating from the
      ovarian stroma. Only seven cases have been reported, all in postmenopausal women,
      except for one in a 15-year-old girl. In the present case, masculinization
      developed over a few months in a 24-year-old woman. The serum concentration of
      testosterone was 4.7 ng/ml before operation. Left salpingo-oophorectomy and wedge
      resection of the right ovary were performed. The encapsulated left ovarian tumor
      was an ovarian stromal Leydig cell tumor on microscopic examination.

PMID- 10202679
TI  - Mixed malignant germ cell tumor of the fallopian tube.
AB  - Immature teratomas of the fallopian tube are exceedingly rare with only three
      reported cases in the English literature. Reported here is a case of primary
      mixed malignant germ cell tumor of the fallopian tube composed of immature
      teratoma and yolk sac tumor.

PMID- 10202680
TI  - Transitional cell metaplasia of the uterine cervix.

PMID- 10202681
TI  - Localized amyloidosis of the uterine cervix with spheroid type of amyloid.

PMID- 10202682
TI  - [An important task even in the HAART era (High Activity Anti-Retroviral Therapy).
      Infection management in HIV-patients].

PMID- 10202683
TI  - [Imipenem/cilastatin sodium and other beta-lactams for respiratory tract
      infections: clinical benefit and treatment days for cure].
AB  - Therapeutic efficacy and the treatment days for cure of imipenem/cilastatin
      sodium (IPM/CS) in treatment of pulmonary infections were prospectively
      determined in comparison with those of beta-lactams other than carbapenems mainly
      ceftazidime (CAZ) or sulbactam/cefoperazone (SBT/CPZ). The overall response rate
      was 84.9% (62/73) in the IPM/CS group and 74.7% (56/75) in the beta-lactam group,
      the difference not being significant. In the subjects having underlying
      respiratory diseases, the response rate was 91.1% (41/45) and 73.9% (34/46) in
      the IPM/CS and beta-lactam groups, respectively. In patients with infections
      secondary to chronic respiratory disease, the rate was 91.2% (31/34) in the
      former group and 66.7% (24/36) in the latter group, respectively. The differences
      were significant for both stratified analyses. The treatment days for cure judged
      by the attending physician were 12.9 +/- 0.6 days in the IPM/CS group, and 14.5
      +/- 0.7 days in the beta-lactam group. The difference was not, however,
      significant. In patients with mild to moderate infections, the treatment days for
      cure was 12.0 +/- 0.6 days (n = 64) in the IPM/CS group and 14.3 +/- 0.7 days (n
      = 70) in the beta-lactam group. In patients with underlying respiratory disease,
      the treatment days for cure were 11.8 +/- 0.7 days (n = 45) and 14.7 +/- 0.9 days
      (n = 46) in the IPM/CS and beta-lactam groups, respectively. In patients with
      infections secondary to chronic respiratory disease, the days were 11.1 +/- 0.7
      days (n = 34) and 14.7 +/- 1.1 days (n = 36), respectively. Thus, IPM/CS therapy
      significantly reduced the number of treatment days until cure. There was,
      however, no significant difference between the two therapy groups in treatment of
      the patients with severe infections, those without underlying respiratory
      disease, or those with pneumonia and/or lung abscess. The treatment days for cure
      were also assessed by the members of review committee taking into consideration
      of body temperature, leukocyte count, and C-reactive protein. As the result, it
      was 6.9 +/- 0.5 days in the IPM/ CS and 10.3 +/- 0.7 days in the beta-lactam
      groups; respectively, and the difference was significant. Time (days) until cure
      was also compared between the two groups using survival time analysis, confirming
      a more rapid response in the IPM/CS group. Although IPM/CS therapy was associated
      with a shorter response time as assessed by both the attending physicians and the
      review committee, there were considerable differences between the results of
      these judgements. Thus, the duration of treatment with injectable antibiotics
      requires reevaluation in the future. No significant differences were observed
      between the groups with respect to parameters indicating side effects and
      laboratory abnormalities. There were no severe symptoms or laboratory findings,
      and symptoms and changes in laboratory values, if any resolved during the course
      of therapy or after the withdrawal of treatment. In conclusion, IPM/CS seems to
      be very useful as first-line therapy for respiratory tract infections and for
      shortening the duration of treatment.

PMID- 10202684
TI  - [Pharmacokinetic analysis of cefozopran in neonatal infections--population
      pharmacokinetics using nonmem].
AB  - This report describes the results on pharmacokinetics, efficacy and safety of
      cefozopran (CZOP) in neonatal patients. Enrolled patients were 136 in total whose
      informed consents to enter this study had been given by their parents. Among
      them, blood samples were collected from 42 neonates to analyze concentrations of
      CZOP by population pharmacokinetics (PPK) methods. Based on this analysis, the
      average pharmacokinetic parameters of CZOP and the variabilities of them in
      different morbid pharmacological backgrounds and in different subjects were
      evaluated. This PPK analysis showed that clearance (CL) and distribution volume
      (Vd) of CZOP could be estimated by the following equations; CL = 0.0452 x WT1.75
      (in the case of the postnatal age of over than 1 day) CL = 0.623 x 0.0452 WT1.75
      (in the case of the postnatal age of 1 day or less) Vd = 0.455 x WT where WT
      indicates body weight in kg. The coefficients of variation among individual
      subjects on CL and Vd were found to be 20.7% and 20.0%, respectively. From this
      PPK analysis it was indicated that the elimination of CZOP is dependent on the
      postnatal age and is approximately 38% lower in the younger group than in the
      older group. Therefore, it could be concluded that, though the cases of
      evaluation were small in number, adjustment of dosing of CZOP is necessary,
      particularly in prolongation of intervals of administration, in cases of
      postnatal age of 1 day or less.

PMID- 10202685
TI  - [Study on the therapeutic effect of panipenem/betamipron on perinatal infection
      in pregnant women].
AB  - An investigation was carried out to determine the therapeutic effect of
      panipenem/betamipron (PAPM/BP), a injectable carbapenem antimicrobial agent, on
      infections in pregnant women during perinatal period. Of the 41 patients enrolled
      in the study, 34 were subjected to the analysis, with 1 exemption because of
      protocol violations (regimen), 3 because of uncertain evidence symptoms of
      infection, and 3 because of failure to undergo laboratory tests. PAPM/BP was
      administered by intravenous drip infusion at doses of 0.5 g twice or three times
      a day daily for periods of 3 to 14 days. The efficacy rate according to the
      evaluation of the Drug Efficacy Evaluation Committee and the attending physicians
      was 79.4% (27/34), with 49 of the 61 clinical isolates (80.3%) being eradicated.
      Safety was evaluated as "safe" in 39 of the 41 assessable patients (94.1%). Mild
      headache and nausea were experienced by 1 patient (2.4%) as adverse drug
      reactions, but the symptoms disappeared after the completion of treatment. Slight
      elevations of GOT, GPT and LDH in laboratory tests were observed in 1 patient
      (2.4%), but these values returned to normal after the completion of treatment.
      These results suggested that PAPM/BP may be a useful drug in the treatment of
      bacterial infections during the perinatal period. To firmly establish its safety,
      however, further clinical and pharmacokinetic studies are needed in larger
      populations.

PMID- 10202686
TI  - [Pathogenecity of fosfomycin-resistant strains isolated from Escherichia coli].
AB  - Two fosfomycin-resistant strains, FRC14 (parent strain, Escherichia coli [E.coli]
      c73-18) and FRK104 (parent strain, E. coli O124), were isolated from spleens
      before the bacterial disappearance, after inoculating the parent strains
      intraperitoneally into mice and treating them with a single oral dose of
      fosfomycin. The resistant strains were successfully isolated by a replica method
      from a mass of sensitive cells of respective parent. To elucidate the
      pathogenesis of the resistant strains, their characteristics were investigated.
      The MIC of fosfomycin for FRC14 was 25 micrograms/ml (4 times the MIC for the
      parent) and that for FRK104 was 100 micrograms/ml (8 times the MIC for the
      parent). The strain FRC14 showed a defective utilization of sn-glycerol 3
      phosphate (G3P), but utilization of other carbohydrates was similar to that of
      the parent strain. Thus, the strain FRC14 seemed to be a glpT mutant. The strain
      FRK104 did not use variety of carbohydrates including G3P, but used glucose 6
      phosphate. The utilization of G3P was recovered in the presence of cAMP. Thus,
      the strain FRK104 seemed to be a ptsI mutant. These resistant strains were
      diminished their killing activity for mice in comparison to that of the each
      parent strain when they were inoculated intraperitoneally. The cell number of
      FRC14 decreased or disappeared in blood and spleen in mice, while that of the
      parent increased. The strain FRK104 diminished its ability of producing
      keratoconjuctivitis in guinea pigs in comparison to that of the parent strain.

PMID- 10202687
TI  - [Effects of isepamicin and beta-lactam antibiotics on the release of endotoxin
      from Pseudomonas aeruginosa].
AB  - Antibiotic-induced release of endotoxin (lipopolysaccharide, LPS) from
      Pseudomonas aeruginosa was investigated in in vitro with different antibiotic
      concentrations and in the pharmacokinetic autosimulation system. We compared the
      effect of isepamicin (ISP) with those of 3 beta-lactam antibiotics, piperacillin
      (PIPC), ceftazidime (CAZ) and imipenem (IPM). ISP showed a strong bactericidal
      activity, but the amount of free LPS did not increase by 6 hrs (28 +/- 2 ng/ml at
      1MIC). PIPC and CAZ caused a gradual killing and a large amount of LPS release at
      4 hrs (515 ng/ml and 493 ng/ml, respectively, at 1 MIC). At 1/4 x MIC, PIPC and
      CAZ did not reduce colony forming counts and induced more release of free LPS.
      The organism treated with IPM released less LPS, while it was killed rapidly. The
      viable cell counts decreased dramatically after administration of ISP in the
      pharmacokinetic autosimulation system. ISP inhibited the bacterial regrowth and
      the following release of free LPS by 8 hrs. Great amounts of free LPS were
      released 4 hrs after the administration of PIPC and CAZ in the simulation system,
      associated with morphological changes; elongation, cell lysis or regrowth. IPM
      showed a strong bactericidal activity and less liberation of free LPS, but the
      free LPS level increased at 8 hrs, accompanied by the regrowth of the organism.
      The total amounts of LPS released by P. aeruginosa PAO1 in 8 hours of the
      pharmacokinetic simulation system were as follows; ISP < IPM < CAZ < PIPC.

PMID- 10202688
TI  - Comparative studies on in vitro activities of kasugamycin and clinically-used
      aminoglycoside antibiotics.
AB  - Kasugamycin, a unique aminoglycoside antibiotic, has been used for many years
      solely for crop protections. In general, aminoglycoside antibiotics possess broad
      and strong inhibitory activity against both Gram-positive and -negative bacteria,
      however, kasugamycin merely exhibits limited activity against phytopathogenic
      microbes such as Pyricularia oryzae and certain strains of pseudomonads.
      Recently, in human and animal chemotherapy, it has been seriously concerned about
      the emergence of multiply resistant bacteria by consumption of a large amount of
      antibiotics not only for therapy but also for growth-promotion of farm animals.
      It was believed that kasugamycin, the agricultural antibiotic, does not undergo
      any cross-resistance with other clinically important aminoglycoside antibiotics
      because of its weak or almost no activity against common pathogenic microbes
      except for some phytopathogenic fungi and pseudomonads. However, no confirmative
      study on this fact has been published so far. In this study, we compared activity
      of kasugamycin with those of twelve clinically used aminoglycoside antibiotics
      against susceptible standard strains and well-characterized aminoglycoside
      resistant strains as well as clinically isolated strains, in order to show the
      least potential of kasugamycin to create cross-resistant human pathogens against
      clinically important aminoglycoside antibiotics.

PMID- 10202689
TI  - [Therapeutic efficacy of a topical antifungal solution preparation formulated
      with pyrrolnitrin and clotrimazole in combination (Pyroace W) in guinea pig model
      of tinea pedis].
AB  - The therapeutic efficacy of a topical antifungal solution containing a mixture of
      0.2% pyrrolnitrin and 0.4% clotrimazole (Pyroace W) was tested in a guinea pig
      model of tinea pedis using a 1% newly solution formulated preparation of
      miconazole (Dermalin-L) as a reference drug. Infected animals were treated once
      or twice daily with the testing drug and once daily with the reference drug for 4
      weeks. Therapeutic efficacy was evaluated on the basis of the extent of the yield
      of fungal cultures from the infected skin tissues (infection intensity) and the
      relative number of culture-negative animals at the end of the treatment period.
      In an animal group treated once daily with the testing drug, the infection
      intensity was significantly lower than that for untreated or vehicle-treated
      control group (p < 0.0001) although there was no culture-negative animal. A
      similar extent of therapeutic efficacy was obtained with a once daily treatment
      with the reference drug, yielding one of ten culture-negative animal. A better
      efficacy was seen in animals treated twice daily with the testing drug; the
      infection intensity was further decreased to a significant level and eight of ten
      animals became culture-negative. These results demonstrated that twice daily
      treatment with the testing drug was highly effective in guinea pig model of tinea
      pedis, 80% of infected animals being mycologically cured. It confirms the
      clinical usefulness of this regimen in the treatment of patients with tinea pedis
      or other types of dermatophytosis.

PMID- 10202690
TI  - Generational differences in psychosocial adaptation and predictors of
      psychological distress in a population of recent Vietnamese immigrants.
AB  - While first-wave Vietnamese immigrants adapted well to life in the United States,
      subsequent immigrants have had greater adjustment difficulties, including more
      evidence of psychological distress. This study aimed to analyze psychosocial
      adaptation differences among three generations of recent Vietnamese immigrants,
      as well as to examine predictors of mental distress in the sample as a whole. A
      community sample of 184 recent Vietnamese immigrants, categorized as either
      elderly, middle-aged, or young adults, was assessed for levels of psychological
      distress, including depression, anxiety, and PTSD, as well as family conflict,
      dissatisfaction with life in the U.S., acculturation and biculturalism, social
      support, coping, and premigratory stressors. Young Vietnamese adults were most
      acculturated, most bicultural, and reported themselves as healthiest and least
      depressed. They were most often working, least often on welfare, and had the
      highest family income. However, they also reported most dissatisfaction with
      their current lives in the U.S. and most family conflict. Regression analysis
      explaining approximately one-quarter of the variance in mental distress
      implicated current dissatisfaction with and lack of adjustment of life in the
      United States, as well as greater acculturation and increased family conflict.
      Although young adults scored significantly higher than other generations on most
      of the risk factors for psychological distress, they appeared to be buffered
      against poorer mental health outcomes by factors of generation and perceived
      positive overall well-being. In terms of testing a predictive model of
      psychological distress, this study found current adjustment factors significantly
      more important in determining mental health outcomes than premigratory stressors
      such as war-related traumas.

PMID- 10202691
TI  - Predictors of compliance with recommended cervical cancer screening schedule: a
      population-based study.
AB  - BACKGROUND: The prevalence of routine cervical cancer screening and compliance
      with screening schedules are low compared to the Year 2000 objectives.
      Identifying predictors of routine screening and screening schedule compliance
      will help achieve these objectives. METHODS: We analyzed data from probability
      samples of 1,609 Missouri women responding to both the 1994 Behavioral Risk
      Factor Surveillance System (BRFSS) and the Missouri Enhanced Survey (ES). We
      generated prevalence odds ratios to identify predictors of non-compliance to
      cervical cancer screening guidelines. Also, among a sample of women reporting a
      reason for last Pap test, we estimated the relative odds of a screening v.
      diagnostic exam. RESULTS: In the combined probability sample, compliance with
      screening schedule was likely among women younger than 50 years of age and women
      who had either a recent mammography or a clinical breast exam. Being African
      American, not experiencing a cost barrier when seeking medical care, having at
      least a high-school education and health coverage were each associated with an
      increased compliance with a screening schedule in the combined probability
      sample. Among women in the combined probability sample, whites, those who
      experienced no cost barrier to seeking medical care, the non-obese, and those who
      had a recent mammography were each more likely to have had a screening as opposed
      to a diagnostic exam. DISCUSSION: Cancer control and cardiovascular (CVD)
      prevention programs should consider jointly targeting those at high risk for
      cervical cancer and CVD because of aging and associated high-risk behavior such
      as non-compliance with cervical cancer screening, smoking, and obesity. Also,
      further research is needed to examine whether the increased compliance with
      cervical cancer screening guidelines among African American women may be in part
      due to higher occurrence of diagnostic Pap smears.

PMID- 10202692
TI  - Anabolic-androgenic steroid use among high school football players.
AB  - Eight-hundred seventy-three Indiana high school football players were surveyed to
      investigate the use of anabolic-androgenic steroids (AAS). Subjects were varsity
      football players that were randomly selected from 27 high schools throughout
      Indiana. Out of a possible 1,325 subjects, 873 or 66% participated in the study.
      Subjects completed a 50 item questionnaire that measured demographic information,
      perceived use of AAS, reasons for use, and how AAS are taken. The results
      indicate that 6.3% of Indiana high school football players were current or former
      AAS users. The average age at time of first use of AAS was 14 years and 15% began
      taking before the age of ten. Almost half of respondents indicated they could
      obtain AAS if they so desired, and that other athletes, physicians, and coaches
      were listed as sources for AAS. Athletic trainers can play a vital role in
      disseminating accurate information about AAS abuse, including the long-term
      adverse health risks. These messages should begin with students and athletes as
      early as the fourth and fifth grades and delivered as often as possible
      throughout the school years.

PMID- 10202693
TI  - Accessibility and perceived value of health services in five western Illinois
      rural communities.
AB  - The purpose of this study was to determine the accessibility and perceived value
      of health services in five selected rural communities in South Fulton County,
      Illinois. The Health Services Accessibility and Value Scale (HSAVS) component of
      the larger Fulton County Health Care Survey was used in the investigation. The 12
      items comprising the HSAVS surveyed participant perceptions relative to medical,
      dental, nursing, and public health department services available to them as rural
      residents. The HSAVS was completed by 1709 subjects. The reliability of the HSAVS
      was assessed by computing coefficient alpha. The scale had acceptable internal
      consistency reliability (alpha = .7884). To examine the construct validity of the
      scale, a principle component factor analysis was completed. This analysis
      resulted in a four factor solution which accounted for 66.6% of the cumulative
      total variance. Item means were calculated and were used to rank the HSAVS
      statements. Emergency and primary medical services were valued the most by the
      survey participants. Relatively high in importance to the rural residents
      surveyed were access to pharmacy, eye care, dental care, and immunization
      services. Availability of home health care, transportation to and from health
      care facilities, and access to mental health services were considered to be of
      lesser value to persons living in the rural area studied. Of least importance
      were alcohol and other drug counseling services, prenatal care/well baby
      services, and family planning services. HSAVS total scores and individual
      statements were also analyzed by sex, age, place of residence, and income and the
      results were reported.

PMID- 10202694
TI  - The challenges of employing performance monitoring in public health community
      based efforts: a case study.
AB  - The development of community-based coalitions has acquired great popularity as a
      health promotion strategy. The Institute of Medicine recommends that community
      based health coalitions employ a performance monitoring process in their efforts.
      The results of the current study indicate that in the community setting,
      implementing a performance monitoring process and sustaining the specialized
      functions entailed in this strategy are challenging. Many of the challenges
      result from fundamental differences between the organizational environment of
      bureaucracies--in which these techniques are developed, supported, and greatly
      successful--and the realities of the loosely-structured and resource-limited
      community environment. The performance monitoring process is measurement-driven.
      One challenge of implementing this process at the community level is that public
      health problems of local concern are not always documented in current
      surveillance systems and thus a performance monitoring strategy is not always, or
      immediately, applicable. When data which document a health problem of local
      concern are available, a second challenge facing community-based coalitions is
      acquiring the resources, especially the wide-range of specialized expertise,
      required to fully implement and sustain the performance monitoring process. These
      issues are examined in the context of the Massachusetts Department of Public
      Health's Community Health Network Area (CHNA) Initiative which entails the
      formation of coalitions of local health service providers. The CHNA initiative is
      a statewide project in which health service providers in specified geographic
      regions work collaboratively on health improvement projects.

PMID- 10202695
TI  - A calibration service for biomedical instrumentation maintenance laboratories.
AB  - An in-house calibration laboratory for the Biomedical Instrumentation Maintenance
      Services of the hospitals in the West of Scotland was established in 1993. This
      paper describes the development of this calibration service in the context of an
      overall quality system and also estimates its costs. Not only does the in-house
      service have many advantages but it is shown to be cost effective for workloads
      exceeding 260 items per annum.

PMID- 10202696
TI  - Electrogastrographic impact of multi-site functional gastric electrical
      stimulation.
AB  - Microprocessor-controlled multi-site functional gastric electrical stimulation
      using synchronized higher frequency (above 25 Hz) bipolar voltages has been
      suggested as a possible new avenue towards efficient artificial control of
      gastric motility. However, the effect of this sequential stimulation on gastric
      electrical activity is unknown. Because of the substantial strength of the
      invoked sequential contractions, using implanted electrodes to assess gastric
      electrical activity (GEA) in experimental animals is difficult, if not
      impossible. Electrogastrography (EGG), the non-invasively obtained recording of
      GEA, provides an excellent opportunity to study the changes associated with the
      multi-site functional stimulation. In this study, we investigated 4 unconscious
      dogs with 4 circumferential sets of subserosally-implanted stimulating electrodes
      and 4 force transducers attached close to each stimulating electrode set at
      operation. The abdominal cavity of each dog was closed after the electrode
      implantations and 3 standard neonatal electrocardiographic electrodes were
      attached overlying the abdominal projection of the gastric axis. Two-channel EGG
      recordings were obtained for 1/2 h before any electrical stimulation and during
      1/2 h of intensive sequential stimulation. Significant changes were observed in
      the EGG pattern during stimulation. These changes were quantified and compared to
      the basal recordings. Our findings indicate that the interrelation between
      spectral changes in cutaneous EGG and mechanical activity of the stomach could be
      far more complex than previously speculated.

PMID- 10202697
TI  - ICP measurement accuracy: the effect of temperature drift. Design of a laboratory
      test for assessment of ICP transducers.
AB  - Intracranial pressure (ICP) monitoring has become the mainstay of multimodal
      neuromonitoring of comatous patients after head injury. In the presence of rising
      ICP and faced with pressures, difficult to control, aggressive measures, such as
      hypothermia may be used. The ICP readings should not be influenced by temperature
      changes. A laboratory test was designed to simulate temperature variations
      between 20 degrees C and 45 degrees C at different pressure levels under
      physiological conditions. Five types of transducers were examined: Epidyn Braun
      Melsungen, ICT/B-Titan Gaeltec, Camino-OLM-110-4B, Codman MicroSensor ICP
      Transducer, Neurovent ICP transducer Rehau Ag+Co. Tests were performed at 6
      different pressure levels between 0 mmHg and 50 mmHg. The results show very low
      drifts of less than 0.15 mmHg degree C-1 for Codman, Epidyn and Neurovent.
      Gaeltec and Camino exhibited higher drifts of 0.18 mmHg and 0.2 mmHg degree C-1
      respectively. Within the temperature range from 35 degrees C to 42 degrees C all
      probes tested show insignificant temperature drift. Whether these results also
      apply to other types of transducers needs further evaluation. Problems and
      requirements related to the design of a laboratory test for the in vitro
      assessment of ICP transducers are discussed in detail.

PMID- 10202698
TI  - Technical note. A design study of a bioelectric amplifier and improvement of its
      parameters.
AB  - A design study of a bioelectric amplifier that has better parameters than
      conventional designs is presented. The design allows the construction of
      bioelectric amplifiers with improved parameters in terms of noise, common mode
      rejection ratio, and input impedance. The voltage gain and bandwidth are easily
      adapted to a wide range of biomedical applications. The experimental results of
      the designed bioelectric amplifier are also included.

PMID- 10202700
TI  - Medical rapid prototyping and 3D CT in the manufacture of custom made cranial
      titanium plates.
AB  - This report describes a new method of custom making cranial titanium plates for
      the repair of skull defects. We have combined 3D CT imaging and surface modelling
      with rapid prototyping (RP) technology to produce physical models of our
      patients' skulls from which custom titanium plates were made. We have expanded
      the use of image processing tools applied to the CT image data to fabricate a
      representation of the skull defect. Medical RP models are relatively expensive
      and particular attention has been paid to developing image processing methods to
      reduce costs. Our technique used the patient as their own model and generated
      data from the contralateral side of the head where appropriate. We present the
      results of 10 patients who have had a custom made cranial titanium plate fitted
      and discuss the models for these cases. The benefits of our custom made titanium
      plates are reduced patient attendances to hospital and a more accurate titanium
      plate which has improved fitting and cosmesis.

PMID- 10202699
TI  - Blood damage, platelet and clotting activation during application of
      radiofrequency or cryoablation catheters: a comparative in vitro study.
AB  - During catheter ablation of cardiac tissue, the insulting stimulus may damage and
      activate the blood. Specifically activation of platelets and the clotting system
      is a potential risk by their formation of thrombi. In this study the effect of
      two different techniques, a radiofrequency and a cryo-application procedure, on
      the activation of platelets and clotting in an in vitro blood circulation model
      was investigated. The radio-frequency procedure induced significantly more blood
      cell damage, platelet activation and clotting than did the cryo-application
      procedure. Macroparticles were circulating in blood after the radiofrequency
      procedure. In the cryo procedure, blood damage was limited to the frozen blood
      spherule around the tip of the catheter. It is concluded that at least in those
      circumstances where blood is directly contacting the tip of the radiofrequency or
      cryo-application catheter, the latter is more safe with regard to thrombus
      formation.

PMID- 10202701
TI  - The Maastricht Cerebral Monitor (MCM) for the neonatal intensive care unit.
AB  - Although long-term monitoring of cerebral activity can be important in neonatal
      intensive care, the complexity of multi-channel EEG makes it less suitable for
      this purpose. In the past, a cerebral function monitor (CFM) was developed that
      analyses EEG. The output parameter of the CFM is a semi-logarithmic amplitude
      distribution resulting from the amplification, bandpass filtering, compression,
      rectification and smoothing of the single-channel EEG. Drawbacks of the CFM
      include its inflexibility and limited single-channel processing capacity and its
      lack of functionality for data storage, review or re-analysis. Modern computers
      are powerful enough that a system can be built which does not have these
      drawbacks. We have developed such a system: the Maastricht Cerebral Monitor
      (MCM). The MCM is a flexible system that not only overcomes the CFM drawbacks but
      also provides advanced signal analysis. It was developed with a software system
      (Poly) for acquisition, high quality real-time display, on-line analysis and
      storage of physiological signals. The MCM processes three EEG signals in the
      amplitude and frequency domains. Other parameters provided by the MCM are
      asymmetry of absolute frequency powers, percentage suppression, mean and 90%
      spectral edge frequency. Electrode impedance is recorded as a measure of quality
      of the recording.

PMID- 10202703
TI  - Laser in situ keratomileusis for myopia of -1.50 to -6.00 diopters.
AB  - PURPOSE: To evaluate the results of laser in situ keratomileusis (LASIK) for the
      correction of low and moderate myopia and astigmatism using the Nidek EC-5000
      excimer laser with a modified algorithm. METHODS: Three hundred and ninety-six
      eyes of 257 patients with myopia ranging from -1.50 to -6.00 D and astigmatism of
      no more than 4.00 D were included. Manifest spherical equivalent refraction,
      uncorrected and spectacle-corrected visual acuity were assessed at 1 month (357
      eyes, 90%), 3 months (220 eyes, 56%), and 6 months (168 eyes, 42%) after LASIK.
      RESULTS: Mean preoperative spherical equivalent refraction was -3.60 +/- 1.27 D
      and mean cylinder was -1.01 +/- 1.08 D. Mean postoperative spherical equivalent
      refraction was -0.12 +/- 0.31 D and mean cylinder was -0.19 +/- 0.33 D. At 6
      months follow-up, 158 eyes (94%) had a mean postoperative spherical equivalent
      refraction within +/- 0.50 D of emmetropia; 168 eyes (100%) were within +/- 1.00
      D. Uncorrected visual acuity was 20/20 or better in 81% (136 eyes) and 20/40 or
      better in 100%. Two eyes (1.2%) lost 1 line of spectacle-corrected visual acuity
      due to a decentered ablation. No eye lost 2 or more lines of spectacle-corrected
      visual acuity. CONCLUSION: Our modified LASIK algorithm with the Nidek EC-5000
      excimer laser resulted in safe and predictable outcomes for treatment of low and
      moderate amounts of myopia and astigmatism.

PMID- 10202702
TI  - Worst-Fechner biconcave minus power phakic iris-claw lens.
AB  - OBJECTIVE: Evaluation of long-term results of correction of high myopia by
      implantation of a biconcave Worst-Fechner minus power iris-claw lens into phakic
      eyes. METHODS: One hundred and twenty-seven eyes of 70 patients were implanted
      with the phakic IOL between November 1986 and November 1991. The mean
      preoperative spherical equivalent refraction was -14.29 +/- 5.77 D (range -5.00
      to -31.75 D). The total population decreased from 127 to 68 eyes (53.5%) at the 8
      year examination. By this time, 26 of the 70 patients (37%) had been lost to
      follow-up for unknown reasons. Corneal endothelial density was estimated by
      comparing the image gained by non-contact specular microscopy with a graduated
      reticule (Karickhoff method). RESULTS: At the 6-month examination, mean deviation
      of achieved from calculated refractive correction was +0.52 +/- 1.46 D (range 
      2.25 to +6.50 D). Seventy-seven eyes (62.1%) deviated 1.00 D or less, and 15 eyes
      (12.1%) deviated by more than 2.00 D from the calculated correction. A refractive
      outcome of +/- 1.00 D was attempted in 68 eyes (54% of the 124 eyes) and was
      achieved in 51 eyes (75%). Mean spectacle-corrected visual acuity preoperatively
      was 0.54 +/- 0.27 (range 1.20 to 0.05). At the 6-month examination it was 0.73 +/
      0.3, and by the 8-year examination had decreased to 0.65 +/- 0.26. Statistical
      analysis of corneal endothelial cell density revealed a significant correlation
      of endothelial cell loss with age (> or = 45 years), anterior chamber depth (< or
      = 3.4 mm), and IOL power (> or = -11.00 D). Seventeen eyes (13.4%) had a decrease
      in endothelial cell density and projection to 8-year follow-up resulted in a
      decrease in 27% of eyes. Four eyes needed a penetrating keratoplasty. CONCLUSION:
      Implantation of a biconcave Worst-Fechner lens into a phakic eye effectively
      corrected high myopia with a stable refractive outcome, but 13.4% of implanted
      eyes suffered significant progressive reduction of endothelial cell density. This
      style lens is no longer in clinical use.

PMID- 10202704
TI  - Toric laser in situ keratomileusis for myopic astigmatism using an ablatable
      mask.
AB  - BACKGROUND: To assess the results of toric laser in situ keratomileusis (LASIK)
      correction of myopic astigmatism. METHODS: A prospective study was performed over
      a 20 week period for consecutive patients treated for myopic astigmatism.
      Spectacle-corrected visual acuity, uncorrected visual acuity, spectacle
      refraction, videokeratography, and complications were recorded. Vector analysis
      was performed by the ASSORT program. RESULTS: Sixty-five eyes of 42 patients
      underwent toric LASIK with a Summit Technologies Apex Plus excimer laser. Mean
      preoperative spherical equivalent refraction at the spectacle plane was -6.24 +/-
      2.42 D (range, -1.63 to -14.63 D) and mean pre-operative refractive cylinder
      magnitude was 1.99 +/- 1.35 D (range, 0.75 to 7.00 D); mean attempted refractive
      cylinder correction was 1.90 +/- 1.00 D. Six months after LASIK (43 eyes
      followed), mean spherical equivalent refraction at the spectacle plane was -0.40
      +/- 0.55 D and 31 eyes (72.1%) were within +/- 0.50 D of emmetropia. At 6 months,
      mean refractive cylinder magnitude was 0.74 +/- 0.70 D, mean surgically induced
      astigmatism was 1.46 +/- 0.86 D, mean absolute angle of error was 10.33 degrees,
      mean astigmatic correction index was 0.93 +/- 0.36 D, and mean index of success
      was 0.46 +/- 0.39. Uncorrected visual acuity was 6/12 or better in 34 eyes
      (79.1%) and 6/6 in 15 eyes (35%); spectacle- corrected visual acuity was 6/9 or
      better in 41 eyes (95.35%). Six eyes (14.0%) lost 1 line of spectacle-corrected
      visual acuity at 6 months and one eye (2.3%) lost 2 lines. Ten eyes (23.3%)
      gained 1 line at 6 months. CONCLUSION: Toric LASIK with an ablatable mask using
      the Summit Apex Plus excimer laser is a safe and relatively accurate procedure
      for the correction of myopic astigmatism.

PMID- 10202705
TI  - Evaluation of corneal flap dimensions and cut quality using a manually guided
      microkeratome.
AB  - BACKGROUND: To evaluate reproducibility of corneal flap dimensions and cut
      quality with repeated blade use with a manually guided microkeratome in pig eyes.
      METHODS: Corneal flaps were created using a manually guided microkeratome (Model
      One, Moria) with an intended 130-microns cut depth in 130 enucleated pig eyes.
      Flap thickness was calculated by pachymetry and diameter was estimated by means
      of applanation lenses compared to planimetry. Histology and scanning electron
      microscopy of samples and blades were performed to evaluate the keratectomy
      surface and blade cutting edge after repeated use of the blades. RESULTS: Mean
      flap central thickness was 135 microns (SD, 37 microns). The mean diameter of 8.4
      mm (SD, 0.4 mm) correlated significantly (P < .001) to the intended diameter (r =
      .79). Mean difference from the intended diameter was 0.8 mm (SD, 0.3 mm; range,
      0.04 to 1.4 mm). Scanning electron microscopy showed even and smooth cuts with
      chatter lines at the keratectomy edge using new blades. After repeated blade use,
      increasing cut irregularity, folds, and tissue remnants on the corneal bed
      surface, and nicks and tissue remnants at the cutting edge of the blades were
      observed. CONCLUSION: Reproducible flap dimensions were obtained using the Moria
      One microkeratome on pig eyes. The cut surface was regular and smooth with a new
      blade, but surface quality deteriorated considerably after repeated use of the
      same blade.

PMID- 10202706
TI  - Early corneal topography patterns after excimer laser photorefractive keratectomy
      for myopia.
AB  - OBJECTIVES: We defined early patterns of corneal topography following excimer
      laser photorefractive keratectomy (PRK) with a Summit Apex laser without
      pretreatment software, investigated changes in patterns over time, and identified
      factors associated with different topography patterns. METHODS: Fifty-eight eyes
      of 39 myopic patients were studied. EyeSys videokeratography data were analyzed
      at 1 week and 1, 2, and 3 months after surgery and were classified using a
      standardized classification system. RESULTS: At 1 week, 4.3% (n = 2) of corneas
      showed a homogeneous topography, 0.0% showed a toric-with-axis configuration,
      2.2% (n = 1) showed a toric-against-axis configuration, 8.7% (n = 4) showed an
      irregularly irregular topography, 17.4% (n = 8) showed a keyhole pattern, 23.9%
      (n = 11) showed a semicircular pattern, 41.3% (n = 19) showed a central island
      pattern, and 2.2% (n = 1) showed focal topographic variants. From 1 week to 1
      month, 78.9% of maps changed; from 1 to 2 months, 33.3% of maps changed; and from
      2 to 3 months, 40.0% of maps changed, generally to more regular patterns. The
      central island pattern, which predominated at 1 week, was not seen at 3 months;
      most had changed to the keyhole or semicircular pattern. An association was found
      between the central island pattern and irregularity of reflected rings on the
      video-image of the cornea (P = .05). CONCLUSIONS: The central island pattern is
      an early and usually transient topography pattern following PRK. Keyhole and
      semicircular patterns taken together were the most prevalent in the early
      postoperative period. In some cases, central islands may be a consequence of
      corneal epithelial irregularity, and the meridional orientation of the keyhole
      and semicircular patterns suggests an influence of epithelial healing over time.

PMID- 10202707
TI  - Factors that influence patient choice of contact lens or photorefractive
      keratectomy.
AB  - OBJECTIVE: To explore characteristics of patients and factors that influence
      their decision in selecting photorefractive keratectomy (PRK) and contact lenses.
      METHODS: A questionnaire was presented to 255 PRK and 240 contact lens patients,
      covering patient demographics, refraction, reasons for choosing PRK or contact
      lens, and advice from clinicians or friends/relatives. RESULTS: Mean patient age
      was 37 years for PRK and 26 years for contact lens (P < .0001). The magnitude of
      the mean spherical equivalent refraction in the better eye was 4.14 D for PRK and
      3.26 D for contact lens. Advertising influenced 36% (n = 92) of PRK compared to
      17% (n = 41) of contact lens patients. In the PRK group, 52% (n = 133) opted for
      PRK based on cost; in the contact lens group the cost of PRK was thought to be
      high by 68% (n = 163). Eighty-four percent (n = 214) of the PRK group were
      contact lens wearers; of these, 32% (n = 68) were intolerant to contact lenses
      and 13% (n = 28) were intolerant to lens care solutions. Fifty-six percent (n =
      134) of the contact lens group were concerned about the long-term effects of PRK
      and 49% (n = 118) were afraid to undergo a surgical procedure. CONCLUSIONS: PRK
      patients were significantly older but had only marginally higher refractive error
      than contact lens patients. Many patients appeared to discontinue contact lens
      use due to tolerance problems.

PMID- 10202708
TI  - Photorefractive keratectomy with a small spot laser and tracker.
AB  - BACKGROUND: The Autonomous Technologies LADARVision excimer laser system utilizes
      an eye tracking mechanism and a small spot for photorefractive keratectomy.
      METHODS: One hundred and two eyes of 102 patients were treated for -1.50 to -6.25
      D of spherical myopia at the spectacle plane using a 6-mm diameter ablation zone.
      One year follow-up was available for 93 eyes (91%). RESULTS: Uncorrected visual
      acuity for eyes treated for distance vision was 20/40 or better in 99% (n = 90),
      and 20/20 or better in 70% (n = 64) of eyes at 12 months. Spectacle-corrected
      visual acuity was 20/25 or better in all 92 eyes reported; no eye lost more than
      2 lines of spectacle-corrected visual acuity, and only 1 eye (1.0%) experienced a
      loss of 2 lines (20/12.5 to 20/20) at 1 year. The refractive result was within +/
      0.50 D of the desired correction in 75% (n = 70), and within +/- 1.00 D in 93%
      (n = 86) of eyes at 12 months. Refractive stability was achieved between 3 and 6
      months. Corneal haze was graded as trace or less in 100% of the 93 eyes. No
      significant reductions were noted in contrast sensitivity or endothelial cell
      density. CONCLUSIONS: Patients treated with the Autonomous Technologies
      LADARVision excimer laser system for -1.50 to -6.25 D of spherical myopia with 1
      year follow-up had uncorrected visual acuity of 20/20 or better in 70%, no
      significant loss of spectacle-corrected visual acuity, no reduction of
      endothelial cell density or contrast sensitivity, and low levels of corneal haze.

PMID- 10202710
TI  - Lift-flap retreatment after laser in situ keratomileusis.
AB  - PURPOSE: To demonstrate the effectiveness of lifting the flap for retreatment of
      undercorrected eyes after laser in situ keratomileusis (LASIK). METHODS: We
      reviewed the results of 11 LASIK patients (12 eyes) who underwent retreatment for
      residual myopia by lifting the previously cut flap. This was followed by
      treatment with the Summit Apex excimer laser and repositioning of the flap.
      Average time prior to retreatment was 5 months (range, 1 to 9 mo). Follow-up was
      100% at 3 months after retreatment. RESULTS: The average preoperative spherical
      equivalent refraction was -8.73 D; average prior to retreatment was -2.24 D
      (range, -0.67 to -5.75 D). At 1 month after retreatment, average deviation from
      intended correction was 0.08 D; at 3 months it was -0.12 D. Eleven of 12 treated
      eyes (92%) had uncorrected visual acuity of 20/40 or better and 4 eyes (33%) saw
      20/20 or better without correction. Six eyes (50%) were within +/- 0.50 D of
      intended correction at 3 months. No patients lost any lines of spectacle
      corrected visual acuity. CONCLUSION: Retreatment of residual myopia after LASIK
      by lifting the flap appears to be effective and associated with minimal
      complications.

PMID- 10202709
TI  - In perspective: eye tracking and autonomous laser radar.

PMID- 10202711
TI  - Laser thermal keratoplasty using a continuous wave diode laser.
AB  - BACKGROUND: Laser thermal keratoplasty is currently performed with a pulsed
      Ho:YAG laser at 2.07 microns wavelength. Long-term stability depends critically
      on the coagulation depth of each cone and thus on emission wavelength (absorption
      in corneal tissue) and focusing, all contributing to controlled stable collagen
      shrinkage. To achieve this, a temperature range of 65 degrees to 90 degrees C is
      needed. A continuous wave laser source meets the coagulation requirements more
      effectively by avoiding tissue cooling by thermal diffusion as well as the peak
      temperatures of pulsed lasers, which counteracts the intended central corneal
      steepening. METHODS: A continuous wave diode laser was developed, emitting at
      1.885 microns with a maximal energy output of 450 mW. In a contact focusing
      application, the absorption depth in water as a function of wavelength was
      measured. Using laser parameters, comparable to those used for a pulsed Ho:YAG
      laser in contact mode, coagulation spots in human cornea were applied for the
      continuous wave diode laser. RESULTS: The macroscopic and microscopic effects of
      the diode laser coagulation on corneas in vitro and in situ were comparable to
      those of the Ho:YAG laser, if a comparable amount of total energy per spot was
      applied. CONCLUSION: Due to better optimized laser-collagen interaction, higher
      corrections and more stable clinical refractive effects appear achievable using
      the continuous wave diode laser.

PMID- 10202712
TI  - Bilateral vs unilateral LASIK.

PMID- 10202713
TI  - Experimental circular keratotomy for astigmatism.

PMID- 10202714
TI  - Late onset regression after myopic keratomileusis.

PMID- 10202715
TI  - Photorefractive keratectomy to correct myopic or hyperopic astigmatism with a
      cross-cylinder ablation.
AB  - PURPOSE: To assess the efficacy and safety of a combined ablation of the steep
      and flat meridian to correct astigmatism with the excimer laser. METHODS: Twenty
      two eyes with myopic, mixed, or hyperopic astigmatism (mean preoperative
      spherical equivalent refraction -4.30 +/- 4.70 D [range, -12.50 to +1.50 D] and
      mean preoperative cylinder magnitude -3.40 +/- 1.40 D [range, -1.50 to -6.00 D])
      underwent PRK with the Nidek EC-5000 excimer laser. The surgical strategy
      involved ablating half the amount of the cylinder (in diopters) along steepest
      meridian, the other half in a subsequent step along the flattest meridian;
      thereafter, the spherical equivalent was corrected. RESULTS: Six months
      postoperatively, mean spherical equivalent refraction was -0.07 +/- 0.87 D and
      mean cylinder was -0.44 +/- 0.36 D. Mean spectacle-corrected visual acuity was
      0.86 +/- 0.13 compared to 0.75 +/- 0.22 preoperatively. Mean corneal haze was
      0.67 +/- 0.31. No patient lost 2 or more lines of spectacle-corrected visual
      acuity and there were no complaints about night halos or glare. CONCLUSIONS:
      Unlike other ablation strategies, the cross-cylinder method creates a smooth
      transition (low dioptric gradient) between the treated and untreated cornea. This
      is achieved by first treating the cylinder and making the corneal surface
      spherical and then ablating the spherical component of the refractive error.

PMID- 10202716
TI  - Algorithm to correct hyperopic astigmatism with the Nidek EC-5000 excimer laser.
AB  - BACKGROUND: The efficacy of a new ablation algorithm for the correction of
      hyperopic astigmatism with the Nidek EC-5000 excimer laser was evaluated.
      METHODS: Twenty-five eyes with mean preoperative hyperopia of +3.76 +/- 1.70 D
      and a mean hyperopic cylinder of 2.20 +/- 0.80 D underwent photorefractive
      keratectomy (PRK) using a new algorithm with the Nidek EC-5000 excimer laser
      (software version 3.0). The new algorithm differed from previous algorithms in
      that less tissue was removed for the same amount of diopters, and there was less
      of a dioptric gradient between the optical zone and the transition zone. Mean
      preoperative spectacle-corrected visual acuity was 0.8 +/- 0.09. Minimum follow
      up was 6 months. RESULTS: Mean postoperative spectacle corrected visual acuity
      (geometric mean) increased significantly to 0.89 +/- 0.1. The mean sphere
      decreased by 3.08 D and the mean cylinder by 1.60 D. CONCLUSION: Hyperopic PRK
      using the Nidek EC-5000 excimer laser with this new algorithm for hyperopic
      astigmatism appears to be safe and effective.

PMID- 10202717
TI  - Effect of an elliptical optical zone on outcome of photoastigmatic refractive
      keratectomy.
AB  - BACKGROUND: This study presents the effect of an elliptical optical zone on the
      accuracy of correction of astigmatism in patients undergoing photorefractive
      astigmatic keratectomy (PARK) for myopic astigmatism. METHODS: We reviewed a
      consecutive case series of 102 eyes that underwent PARK with a Nidek EC-5000
      excimer laser by a single surgeon. Group A consisted of 50 eyes treated using a
      circular optical zone of 6.5 mm x 6.5 mm with a 7.5-mm x 7.5-mm transition zone.
      Group B consisted of 52 eyes treated using an elliptical optical zone of 5.5 mm x
      6.5 mm with a 6.5-mm x 7.5-mm transition zone. Refraction was measured
      preoperatively and postoperatively, and vector analysis was used to study the
      change in astigmatism induced by surgery. RESULTS: Mean correction index improved
      from 75% in Group A to 100% in Group B. Mean angle of error was reduced from 15.8
      degrees in Group A to 7.5 degrees in Group B. Hyperopic shift was reduced from
      +0.70 D in Group A to +0.20 D in Group B. CONCLUSIONS: Excimer laser
      photorefractive astigmatic keratectomy using an elliptical optical zone improved
      the correction index for astigmatic change and reduced the mean angle of error.
      An elliptical optical zone is more effective than the circular optical zone for
      the treatment of astigmatism in patients with compound myopic astigmatism.

PMID- 10202719
TI  - Correction of astigmatism using positive and negative cylinder programs with the
      Nidek EC-5000 excimer laser.
AB  - BACKGROUND: The efficacy of a current program of positive cylinder treatment was
      evaluated and compared to a previous program of negative cylinder treatment.
      METHODS: The authors performed a comparative analysis of 123 eyes (72 patients)
      who underwent LASIK using the Nidek EC-5000 excimer laser with the formula
      developed by Chayet and the positive cylinder (71 eyes of 52 patients) and
      negative cylinder programs (52 eyes of 31 patients). RESULTS: A faster
      stabilization of correction and a marked reduction of stromal tissue ablated were
      obtained with the positive cylinder program than with the negative cylinder
      program. This was directly related to the amount of preoperative ametropia.
      CONCLUSION: The spectrum of ametropias that can be treated with LASIK is
      increased with the positive cylinder program because less tissue is ablated.

PMID- 10202718
TI  - Correction of asymmetric myopic astigmatism with laser in situ keratomileusis.
AB  - BACKGROUND: There are many ways to correct different kinds of astigmatism
      (myopic, hyperopic, mixed) with excimer laser surgery. New methods of correction
      are under development, including toric ablation in both meridians. Corneal
      astigmatism may also be present in asymmetric forms. METHODS: Twenty-one eyes of
      16 patients (5 male, 11 female) with asymmetric myopic astigmatism were studied.
      The spherical component ranged from -2.75 to -9.25 D (mean, -6.15 +/- 0.63 D),
      and the cylinder ranged from 0.75 to 5.00 D (mean, 1.80 +/- 0.13 D). Mean age was
      33 years. All patients underwent laser in situ keratomileusis (LASIK) using the
      Nidek EC-5000 excimer laser and the Hansatome microkeratome (TM 230 HT). RESULTS:
      Three months after LASIK, average spherical component was -0.50 +/- 0.05 D, and
      mean cylinder was -0.52 +/- 0.05 D. Uncorrected visual acuity (0.92 +/- 0.096)
      was close to average preoperative spectacle-corrected visual acuity (0.99 +/-
      0.099). No patients reported double vision. CONCLUSION: When treating asymmetric
      forms of myopic astigmatism, it is possible to obtain good clinical outcomes by
      decentering the toric ablation and calculating the value and axis of the cylinder
      using topographic data.

PMID- 10202720
TI  - Laser in situ keratomileusis nomogram development.
AB  - BACKGROUND: There is no standard laser in situ keratomileusis (LASIK) nomogram
      for the Nidek EC-5000 excimer laser when used with current software versions 2.23
      or 2.25. Nomogram tables developed by various EC-5000 users differ significantly
      from one another. METHODS: We analyzed the results of our first 138 eyes treated
      for myopia and myopic astigmatism with the Nidek EC-5000 excimer laser, model 2b,
      long working distance. In addition to analyzing standard clinical outcomes, the
      correction values entered into the laser were compared to the achieved change in
      refraction for these eyes. A global nomogram parameter was created, incorporating
      the effect of optical zone size and patient age. After observing initial
      overcorrections, we elected to treat most of the eyes using a 20% reduction of
      the attempted spherical correction. RESULTS: The mean value for the attempted
      change in spherical equivalent refraction was -6.85 D. This correction was
      achieved with a standard deviation of -0.04 D at 1 month, -0.08 D at 3 months,
      and -0.09 D at 6 months after LASIK. The postoperative values for the uncorrected
      and spectacle-corrected visual acuity were similar to other published studies.
      However, scatterplots comparing the laser settings to achieved postoperative
      refractions showed a clear 20% trend toward overcorrection. This trend increased
      with patient age and optical zone diameter. CONCLUSIONS: The basic calibration
      values (factory standard) for software versions 2.23 and 2.25 are too aggressive
      for LASIK treatments. When using optical zone diameters of 6 mm and above, the
      spherical refraction values entered into the laser must be reduced by at least
      20%. LASIK nomograms for the Nidek EC-5000 excimer laser should be specific for
      optical zone diameter and patient age.

PMID- 10202721
TI  - Bilateral simultaneous laser in situ keratomileusis.

PMID- 10202722
TI  - Superior hinge laser in situ keratomileusis.
AB  - PURPOSE: The learning curve and experience with the first 400 superior hinge
      laser in situ keratomileusis (LASIK) procedures performed with the Hansatome
      microkeratome are reported. We present information on intraoperative
      complications, management, practical aspects, and the effectiveness of this
      microkeratome used with the Nidek EC-5000 excimer laser. METHODS: All LASIK
      procedures were performed by the authors, according to the traditional technique
      described by Lucio Buratto. Intraoperative complications in the first 400
      superior hinge LASIK procedures were evaluated. RESULTS: Most procedures had no
      complications. Bleeding of the perilimbal corneal vessels was the most frequent
      complication; other complications observed were not considered serious.
      CONCLUSIONS: The superior hinge LASIK procedure with the Hansatome showed an easy
      learning curve, without the serious complications that frequently occur in this
      phase. It was suitable for all the treatments with the Nidek EC-5000 excimer
      laser.

PMID- 10202723
TI  - Laser in situ keratomileusis for hyperopia.
AB  - OBJECTIVE: To evaluate laser in situ keratomileusis (LASIK) ablation zone size
      and its relationship to refractive and visual outcomes in the treatment of
      hyperopia. METHODS: We evaluated retrospectively 40 eyes of 20 patients who had
      LASIK: 20 eyes had a refractive ablation zone ranging from 5.5 to 9.0 mm (Group
      1); Group 2 consisted of 20 eyes with a refractive ablation zone from 5.5 to 8.25
      mm. We used the Nidek EC-5000 excimer laser and the Hansatome microkeratome. Mean
      spherical equivalent refraction was +2.72 D in Group 1 and +2.75 D in Group 2.
      Objective refraction and visual acuity were evaluated over 6 months in both
      groups. RESULTS: Six months after LASIK, mean spherical equivalent refraction in
      Group 1 was +1.00 +/- 0.84 D and in Group 2 it was +0.75 +/- 0.42 D. One patient
      in Group 1 lost 1 line of spectacle-corrected visual acuity; none in Group 2 lost
      lines. Six patients gained 1 to 3 lines from their preoperative spectacle
      corrected visual acuity. CONCLUSIONS: LASIK provides good results for mild and
      moderate hyperopia. LASIK with an ablation zone from 5.5 to 8.25 mm showed better
      predictability and more stable results. However, corneal diameter and the
      thickness and width of the flap appear to be important factors in the feasibility
      of LASIK in hyperopic eyes.

PMID- 10202724
TI  - Bacterial keratitis following laser in situ keratomileusis for hyperopia.
AB  - A 42-year-old Bahraini man had uneventful laser in situ keratomileusis for
      hyperopia (OD: +3.00 +0.75 x 155 degrees; OS: +2.00 +0.50 x 155 degrees). Three
      weeks later, he presented with localized keratitis in his right eye, with
      localized keratitis at the flap margin with stromal edema. Uncorrected visual
      acuity was 20/80 OD with no improvement with pinhole, and was 20/20 OS. Corneal
      smear culture showed a positive growth of Staphylococcus aureus. The patient was
      immediately treated with subconjunctival gentamicin and intensive topical
      ofloxacin 0.3% with systemic cephalosporin. The patient recovered from keratitis
      within 2 weeks and his uncorrected visual acuity OD improved to 20/20. Keratitis
      following LASIK should be treated promptly so that it does not lead to permanent
      reduction in visual acuity.

PMID- 10202725
TI  - Laser in situ keratomileusis for hyperopia after thermal keratoplasty.
AB  - BACKGROUND: The correction of hyperopia remains challenging because regression
      occurs often after treatment. The authors evaluated laser in situ keratomileusis
      (LASIK) using the Nidek EC-5000 scanning slit excimer laser to correct residual
      hyperopia after thermal keratoplasty. METHODS: Twelve eyes underwent hyperopic
      LASIK for residual hyperopia after thermal keratoplasty. All eyes were treated
      using the Nidek excimer laser and Chiron Automated Corneal Shaper. Hyperopic
      correction was done using a 5.5- to 7.5-mm ablation zone. RESULTS: Mean
      preoperative cycloplegic spherical equivalent refraction was +3.31 D (range,
      +1.00 to +6.50 D). Mean preoperative astigmatism was -0.48 D (range, 0 to -2.00
      D). Postoperatively, all eyes achieved a reduction in hyperopia. After 1 year of
      follow-up, the mean refraction was +0.88 D (range, 0 to +1.50 D). Mean
      postoperative astigmatism was -0.38 (range, 0 to -1.50 D). Two eyes experienced
      improvement in visual acuity and 3 eyes had reduced visual acuity, but no other
      vision-threatening complications were reported. The rate of regression was slow
      over 24 months. No morphological changes on the radial thermal scars were
      observed. CONCLUSION: Hyperopic LASIK after thermal keratoplasty is safe and
      effective, and without vision-threatening complications.

PMID- 10202726
TI  - The corneal barrier function in myopic eyes after laser in situ keratomileusis
      and after photorefractive keratectomy in eyes with haze formation.
AB  - BACKGROUND: Corneal barrier function following photorefractive keratectomy (PRK)
      and laser in situ keratomileusis (LASIK) was evaluated to determine corneal
      damage and to compare the amount of corneal trauma associated with haze
      development with the two procedures. METHODS: The PRK and LASIK procedures were
      performed with the Nidek EC-5000 excimer laser. The Chiron Hansatome
      microkeratome was used in the LASIK procedures. We followed 1528 eyes of myopic
      patients (range, -1.00 to -23.00 D) classified into three groups according to
      age. Each group was divided into four subgroups depending on the amount of myopia
      (-1.00 to -2.75 D; -3.00 to -5.75 D; -6.00 to -9.75 D; -10.00 to -23.00 D). In
      eyes with haze formation, haze intensity and postoperative period of haze
      development were evaluated. The corneal uptake was 5.6 carbonfluorescein 5%, and
      a computer program analyzed video slit-lamp corneal images. RESULTS: PRK and
      LASIK increased corneal permeability to fluorescein (2 to 8 weeks after PRK and 4
      to 6 weeks after LASIK). Deeper ablations showed higher corneal fluorescein
      permeability for longer periods. In eyes with haze formation, an increased index
      of corneal fluorescein permeability was observed in the eyes with early
      postoperative haze formation (1 to 2 months) and a decreased index of corneal
      permeability was observed in eyes with late postoperative period haze formation
      (after 3 months). This finding suggests a difference in the haze that developed
      in the early and later postoperative periods. Fluorescein permeability after PRK
      returned to normal in 2 to 8 weeks and remained constant. Following LASIK,
      fluorescein permeability returned to normal in 4 to 6 weeks. Decreasing corneal
      permeability to fluorescein was observed 2 to 6 months after LASIK, and returned
      to normal at 6 months. CONCLUSION: Photorefractive surgery disrupts corneal
      barrier function for up to 6 months postoperatively, even though other clinical
      tests of the cornea may be normal. This finding may help explain some mechanisms
      of pathogenesis of complication development following PRK and LASIK. The
      fluorescein permeability findings demonstrated different mechanisms for early and
      late haze formation after PRK.

PMID- 10202727
TI  - Comparison of photorefractive keratectomy on one eye and laser in situ
      keratomileusis on the other eye of the same patient.
AB  - OBJECTIVE: The aim of this study was to compare the results of excimer laser
      photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) in the
      same patient. METHODS: All consecutive patients who underwent PRK in one eye and
      LASIK in the second eye using the same excimer laser (Nidek EC-5000) and had at
      least 12 months of follow-up were included in this retrospective study (N = 23).
      Uncorrected and spectacle-corrected visual acuity, final spherical equivalent
      refraction, and degree of haze were compared. RESULTS: Mean postoperative
      spherical equivalent refraction in the group of eyes that underwent PRK was +0.73
      D (range, -5.50 to +3.50 D). Mean postoperative spherical equivalent refraction
      in the group of eyes that underwent LASIK was +0.07 D (range, -1.25 to +3.50 D)
      (P = .046). CONCLUSION: In our study, eyes treated with LASIK had better results
      than eyes treated with PRK.

PMID- 10202728
TI  - Effect of carmellose-based artificial tears on the ocular surface in eyes after
      laser in situ keratomileusis.
AB  - BACKGROUND: Strategies to minimize intraoperative ocular surface disturbance and
      accelerate postoperative ocular surface recovery are an important consideration
      to the surgeon. METHODS: Eighteen eyes of 10 patients were randomized to receive
      intraoperative and postoperative non-preserved balanced salt solution or non
      preserved carboxymethylcellulose-based (carmellose) artificial tears. Presence
      and severity of McMonnies dry eye symptom survey score primary dry eye symptoms,
      fluorescein break-up time, and rose bengal staining were graded preoperatively
      and at 1 day, 1 week and 1 month postoperatively. Conjunctival impression
      cytology of the perilimbal conjunctiva was performed 1 month after surgery to
      determine goblet cell density. RESULTS: McMonnies dry eye symptoms were reported
      more frequently for the balanced salt solution group at 1 day, 1 week, and 1
      month after surgery. Fluorescein break-up time was significantly greater in the
      carmellose-based group at 1 day (P < .01), 1 week (P = .04), and 1 month (P <
      .01) after surgery. The rose bengal staining score was significantly greater at 1
      day (P < .01) and 1 week (P < .01) postoperatively for the balanced salt solution
      group. Mean goblet cell density for the carmellose-based group at 1 month
      postoperatively was significantly greater than that for the balanced salt
      solution group (P < .01). CONCLUSIONS: Postoperative and intraoperative use of
      carmellose-based artificial tears resulted in significantly more rapid recovery
      of the ocular surface after LASIK when compared to balanced salt solution.

PMID- 10202729
TI  - Corneal cooling and rehydration during photorefractive keratectomy to reduce
      postoperative corneal haze.
AB  - PURPOSE: An increase in corneal temperature has been implicated in subepithelial
      haze after surface photorefractive keratectomy. We aimed to determine if cooling
      the cornea by means of hydration between ablations and immediately after final
      surface ablation in PRK reduces haze. METHODS: One hundred five eyes of 61
      patients with myopia ranging from -6.00 to -9.75 D were included. One of the
      surgeons irrigated with cool balanced salt solution between ablation passes and
      immediately at the end of the surface ablation while two others did not. Results
      of haze grading were analyzed at the end of 3 and 6 months and 1 year after PRK
      by an independent examiner. RESULTS: Haze was significantly reduced in those eyes
      in which irrigation (cooling) with balanced salt solution was performed
      intraoperatively and immediately after ablation. CONCLUSION: Cooling and
      rehydration of the cornea with chilled balanced salt solution between passes
      during PRK significantly reduces haze in patients with baseline myopia between 
      6.00 and -9.75 D.

PMID- 10202730
TI  - Stimulating re-epithelialization after photorefractive keratectomy.
AB  - BACKGROUND: Re-epithelialization is usually complete in eyes 3 to 4 days
      following photorefractive keratectomy (PRK). However, this process is delayed in
      0.5% of these eyes, leading to early development of haze. The authors
      investigated a method to stimulate re-epithelialization following PRK. METHODS:
      PRK was performed with the Nidek EC-5000 excimer laser. Following surgery,
      express-cytokinotherapy was applied. This method consisted of a single
      subconjunctival injection of 2.5 to 3.0 ml of ex juvanticus mixture of autoblood
      and immunomodulator Poludan. This mixture was then applied topically 4 times a
      day until re-epithelialization was complete. Poludan is an interferon inducer
      (complex polyA: polyU), stimulates expressed production of interferon and
      interleukin-2, and increases natural cytotoxicity. RESULTS: Thirty eyes of 30
      patients with delayed re-epithelialization were treated with the described
      method. The average time to re-epithelialization was 7.00 + 0.64 days. Total
      epithelialization was complete on day 3 + 0.38 after beginning the
      cytokinotherapy (P < .05). Early haze developed in only 2 patients from this
      group. Occurrence of early haze in the control group of patients who had
      persistent epithelial defects 8 to 16 days postoperatively and were given
      traditional therapy--including corticosteroid and non-steroidal drugs--was
      reliably higher: 8 to 10 days (P < .01). CONCLUSION: Local express
      cytokinotherapy appears to be an effective method to promote quick and complete
      epithelialization in eyes following PRK that experience delayed re
      epithelialization. This treatment may be an important part of the prevention of
      early haze development and achievement of better visual acuity.

PMID- 10202731
TI  - Peripheral corneal relaxing incisions for residual astigmatism after
      photoastigmatic keratectomy and laser in situ keratomileusis.

PMID- 10202733
TI  - Photoastigmatic refractive keratectomy for correction of astigmatism after
      keratoplasty.
AB  - BACKGROUND: The efficacy and safety of photoastigmatic refractive keratectomy
      (PARK) to correct astigmatism after keratoplasty was evaluated. METHODS: PARK was
      performed using the Nidek EC-5000 excimer laser in 10 eyes of 10 patients (mean
      age: 49.5 +/- 11.5 years) with astigmatism after keratoplasty. RESULTS: The
      refractive cylinder decreased from 5.80 to 3.20 D, whereas at 6 months,
      topographic cylinder decreased from 7.40 to 5.90 D post-operatively. Five eyes
      (50%) had uncorrected visual acuity of 20/60 or better at 3 months. Stromal haze
      increased from 3 to 6 months postoperatively, and at 6 months, 5 eyes (50%) had a
      haze score of greater than or equal to 2.0. CONCLUSION: PARK is a moderately
      effective method of correcting astigmatism after keratoplasty.

PMID- 10202732
TI  - Treatment of keratoconus with laser in situ keratomileusis, photorefractive
      keratectomy, and radial keratotomy.
AB  - BACKGROUND: The authors investigated the refractive treatment of keratoconus to
      give patients better and more comfortable vision with and without glasses or soft
      contact lenses. METHODS: Patients with spectacle-corrected visual acuity worse
      than 20/40 and conus apex greater than 350-micron thick were treated. We used the
      Nidek EC-5000 excimer laser with a 130-mm plate and special multi-design masks
      for the conus treatment and the Chiron ALK microkeratome. Patients were followed
      for 2 years postoperatively. We also used sector radial keratotomy to treat
      keratoconus. RESULTS: The authors report the advantages of using these new
      techniques to treat keratoconus. Excimer laser ablation should be performed only
      when the cornea surrounding the conus is flat, so that it can join the ablated
      zone (small optical zone) forming a new flat shape, without regression. Ablation
      did not exceed 50 microns with a 3- to 4-mm ablation diameter for up to -6.00 D
      myopic correction. CONCLUSION: The authors hope to avoid or delay the need for
      corneal transplant in keratoconus eyes, giving these patients better vision with
      and without glasses or soft contact lenses.

PMID- 10202734
TI  - Customized and low spherical aberration corneal ablation design.
AB  - PURPOSE: The purpose of this study was to use the Arizona Eye Model to help guide
      customization of corneal excimer ablation and reduce spherical aberration.
      METHODS: Myopic eyes were treated with the Nidek EC-5000 excimer laser with a 5.5
      mm diameter optic ablation zone and a 7.0-mm diameter transition ablation zone.
      We analyzed preoperative and postoperative corneal topographies using height
      mapping. From this data, refractive error profiles and maps were constructed
      using the Arizona Eye Model. The first group of patients had refractions between 
      2.00 and -5.00 D. Data was obtained by subtracting postoperative topography from
      preoperative topography. We then plotted the ideal ablation pattern if no
      additional spherical aberration was introduced when compared to preoperative
      topographies. RESULTS: We found that in the central 4 mm, the ablation pattern
      was highly acceptable, with negligible spherical aberration. As the ablation
      moved out toward 6 mm, there was increasing spherical aberration. Newer ablation
      designs require more flattening in the midperiphery of the cornea. These flatter
      peripheral designs require more blending in the periphery and larger transition
      zones. CONCLUSION: The use of computerized corneal topography in eye modeling is
      helpful in designing new ablation patterns to reduce optical and spherical
      aberration. Ablation zone design is critical to maximizing optical and biologic
      tolerance.

PMID- 10202735
TI  - Irregular astigmatism after photorefractive keratectomy.

PMID- 10202736
TI  - Correlation of laser profilometry scans with clinical results.
AB  - BACKGROUND: The homogeneity of the ablation profile of excimer lasers can be
      disturbed by various reasons. Laser profilometry scans may serve as a
      preoperative laser quality control if they can be correlated with clinical
      results. METHODS: Four lasers from different manufacturers were calibrated for
      normal photorefractive keratectomy. Preoperatively, -3.00 D ablations were
      performed on a standardized PMMA Exci-Check plate. Two- and three-dimensional
      surface scans were taken from the PMMA samples. The optical zone and the ablation
      depth were measured. Surface roughness and regularity of the ablation profile
      were compared. The PMMA ablation depth was plotted with the postoperative
      refraction. Surface regularity was correlated to loss of spectacle-corrected
      visual acuity. RESULTS: The ablation depth on PMMA changed with time in all four
      tested lasers. For one laser we measured an ablation depth between 6 and 9
      microns which we could correlate to a postoperative refraction of -0.50 to +2.00
      D at 2 months after PRK. Surface roughness of these different lasers different
      significantly from each other. Asymmetric ablation profiles produced a loss of
      spectacle-corrected visual acuity. CONCLUSION: This study indicates there may be
      a correlation between results of laser surface profilometry scans and clinical
      outcomes. A more sophisticated quality control than currently available seems
      possible and is necessary. Laser profilometry (Exci-Check) provided detailed
      information about the laser and the ablation conditions, and may help to avoid
      undesirable clinical outcomes from ablation profile irregularities.

PMID- 10202737
TI  - Fully automated refraction in laser refractive surgery using the Nidek COS-2000.

PMID- 10202738
TI  - Confocal scanning laser tomography of the cornea with the total corneal analyzer.

PMID- 10202739
TI  - Photofilters for dimensional contrast sensitivity improvement in patients with
      corneal haze after photorefractive keratectomy.

PMID- 10202740
TI  - Obstructive anomalies of the female reproductive tract.
AB  - Obstructive anomalies of the female reproductive tract preclude the outflow of
      menstruation and may allow the collection of blood in the uterus and/or vagina
      and increase the likelihood of retrograde flow. These conditions occur in young
      women and may result in pelvic masses, endometriosis and/or pain. In addition,
      the long-term sequelae of endometriosis may influence fertility. Pediatricians,
      primary care physicians and gynecologists need to maintain a high index of
      suspicion in order to aggressively diagnose these congenital anomalies in young
      adolescents. In order to maintain this vigilance and assist in maintaining future
      fertility, it is important to review the embryologic sources of these anomalies,
      understand the modes of diagnosis and recognize the treatment options currently
      available.

PMID- 10202741
TI  - Ossein-hydroxyapatite compounds for preventing postmenopausal bone loss.
      Coadjuvant use with hormone replacement therapy.
AB  - OBJECTIVE: To evaluate whether the addition of an ossein-hydroxyapatite compound
      (OHC) may improve the effect of hormone replacement therapy (HRT) on
      postmenopausal bone loss. STUDY DESIGN: Of the 118 recent surgically
      postmenopausal women initially selected for this open study, 96 completed one
      year follow-up. Patients were allocated into four groups. The first group
      received 50 micrograms/d of transdermal 17-beta estradiol continuously (group E,
      n = 23), the second received 3.32 g/d of an OHC every day (group OHC, n = 23),
      the third received 50 micrograms/d of transdermal 17-beta estradiol continuously
      plus 3.32 g/d of the OHC every day (group E-OHC, n = 26), and an additional 24
      women were used as untreated controls (group C). Bone mass, assessed by dual x
      ray absorptiometry, was measured prior to and at the end of treatment. Samples,
      including serum calcium, phosphate and osteocalcine level, were collected before
      therapy and during the 6th and 12th treatment months. RESULTS: All treatment
      groups showed an increase in bone mineral content. This increase was higher in
      the E-OHC group (4.7%, P < .01). Concomitant biochemical effects at 6 and 12
      months were compatible with the observed effects on bone mineral. CONCLUSION: The
      combined regimen of OHC and HRT increased vertebral bone mass in postmenopausal
      women to a greater extent than did OHC or HRT alone, suggesting that this drug
      combination may be useful in the management of postmenopausal bone loss.

PMID- 10202742
TI  - Results of the ACTH stimulation test in hirsute women.
AB  - OBJECTIVE: To determine the incidence of late-onset congenital adrenal
      hyperplasia (LOCAH) due to 21-hydroxylase deficiency among hirsute women and to
      evaluate the results of the ACTH stimulation test with the clinical
      characteristics. STUDY DESIGN: Prospective, controlled study. One hundred women
      with hirsutism and 14 normally cycling women without hirsutism were included in
      this study at the Division of Reproductive Endocrinology, Department of
      Obstetrics and Gynecology, Cerrahpasa School of Medicine, Istanbul University.
      After basal serum progesterone (P) and 17 hydroxyprogesterone (17OHP) levels were
      determined, an ACTH stimulation test was performed on cycle day 3-5. The same
      parameters were checked 30 minutes later. We estimated the 21 hydroxylase
      activity by calculating the change in 17OHP (17OHP 30-0) and the summed rate of
      the change in P and 17OHP ([P30-0] + [17OHP30-01/30 minutes). The 95th percentile
      for these estimates in normal women were calculated, and values above three times
      the 95th percentile were considered to distinguish women with LOCAH due to 21
      hydroxylase deficiency. RESULTS: The 95th percentile for 17OHP 30-0 and (P30-0) +
      (17OHP30-0)/30 minutes in normal women was 1.6 and 8.9 ng/dL/min, respectively.
      Regarding 17OHP 30-0 values, three women with hirsutism had levels above three
      times the 95th percentile of these estimates, and 28 women had estimates of more
      than the 95th percentile but less than threefold. Seventeen of 28 women had
      oligomenorrhea, and all had severe hirsutism. The women with severe hirsutism and
      oligomenorrhea had significantly higher ACTH-stimulated serum 17OHP levels and
      values for 17OHP 30-0 and (P30-0 + (17OHP30-0)/30 min) than did normally cycling
      women. CONCLUSION: The incidence of LOCAH due to 21-hydroxylase deficiency and
      mild 21-hydroxylase deficiency is 3% and 28%, respectively, in women with
      hirsutism. Clinical characteristics are not helpful in determining 21-hydroxylase
      deficiency. However, the incidence of 21-hydroxylase deficiency is more common
      among women with severe hirsutism and oligomenorrhea. The change in serum 17OHP
      30-0 seems to be greater than the summed rate of change in serum 17OHP and P in
      the detection of 21-hydroxylase enzyme deficiency.

PMID- 10202743
TI  - Lysyl oxidase transcripts in peritoneal adhesions and incisional scars.
AB  - OBJECTIVE: To evaluate the role of lysyl oxidase in postsurgical adhesion
      formation and incision wound repair. STUDY DESIGN: Female New Zealand rabbits
      underwent a pelvic-peritoneum adhesion-inducing operation under sterile
      conditions. In brief, the uterine horns were removed from the abdomen and abraded
      with surgical gauze and a scalpel blade. The horns were then replaced into the
      abdominal cavity, the incision was sutured, and the animals were allowed to
      recover. The animals were killed before lesion development and after 2, 4, 8, and
      14 days of postsurgical recovery. The abraded uterine horns, abdominal wall
      incisional wound and a portion of the sidewall peritoneum were then removed.
      Total RNA was extracted using the guanidinium thiocyanate-phenol-chloroform
      method. Northern blot analysis was performed with an [alpha-32P]-labeled lysyl
      oxidase probe. RESULTS: Lysyl oxidase was expressed during abdominal wall
      incision repair on days 2 and 4 of postsurgical recovery, declining thereafter
      (days 8 and 14). In contrast, no increase in lysyl oxidase expression was noted
      in the uterine horns as compared to the control sidewall peritoneum. CONCLUSION:
      Lysyl oxidase plays a differential role in the early stages of abdominal wall and
      uterine horn repair.

PMID- 10202744
TI  - Multiple vs. single betamethasone therapy. Neonatal and maternal effects.
AB  - OBJECTIVE: To identify potential neonatal benefits and possible neonatal and
      maternal complications associated with repeated use of antenatal corticosteroids.
      STUDY DESIGN: A retrospective chart review was done on all gravidas < 34 weeks
      who were hospitalized and received antenatal betamethasone at our institution
      between January 1, 1992 and April 30, 1996. Regression analysis was performed to
      investigate the relationship between single vs. multiple course of betamethasone
      and multiple variables. RESULTS: After controlling for significant covariates,
      multiple courses of betamethasone were associated with a decrease in oxygen use
      (P < .01). A nonsignificant decline in respiratory distress syndrome and assisted
      ventilation was noted. No effect on birth weight or maternal or neonatal
      infection was seen. CONCLUSION: Repeated use of betamethasone is associated with
      a significant decrease in oxygen use in the preterm neonate. No significant
      maternal or neonatal complications were found. A prospective, randomized trial is
      necessary.

PMID- 10202745
TI  - Comparison of magnetic resonance imaging and ultrasonography in the early
      diagnosis of interstitial pregnancy.
AB  - OBJECTIVE: To investigate the usefulness of ultrasonography (USG) and magnetic
      resonance imaging (MRI) in the early diagnosis of interstitial pregnancy. STUDY
      DESIGN: Four cases of interstitial pregnancy that showed characteristic
      ultrasonographic and MRI findings were studied. All cases received cornual
      resection, and the presence of interstitial pregnancy was confirmed by pathologic
      examination. RESULTS: Three of four cases had a gestational sac in the uterine
      cornu or a protruding cornual mass and myometrium between the sac and uterine
      cavity on both USG and MRI. In the remaining case, preoperative diagnosis was
      inconclusive because no gestational sac was demonstrated by USG or MRI. Color
      flow mapping was conducted in three cases and revealed prominent
      peritrophoblastic blood flow. CONCLUSION: The findings suggest that USG combined
      with color flow mapping is the first choice in the early diagnosis of
      interstitial pregnancy. MRI, which is an extremely expensive imaging technology,
      should be used only if transvaginal USG with color flow mapping is inconclusive
      in ruling out the diagnosis of interstitial pregnancy.

PMID- 10202746
TI  - Intrauterine devices. The optimal long-term contraceptive method?
AB  - OBJECTIVE: To review selected data on the effectiveness, safety, cost and
      technical ease of intrauterine device (IUD) use compared with Norplant and
      surgical sterilization. STUDY DESIGN: Literature review. RESULTS: IUDs are highly
      effective, safe and relatively inexpensive methods of contraception that may
      offer advantages for some women over other long-term methods, such as
      sterilization and Norplant. IUDs provide protection against pregnancy comparable
      to that provided by female sterilization, and they may be more effective than
      Norplant. IUDs have a long duration of effectiveness: the copper T 380A (TCu380A)
      is effective for at least 10 years, and the levonorgestrel (LNg) IUD appears to
      be effective for at least 7. Norplant is effective for only five years. Both
      types of IUD can disrupt menstrual bleeding patterns, although the patterns of
      bleeding are different. Copper IUDs often increase blood loss, whereas the LNg
      IUD, like Norplant, substantially reduces menstrual bleeding. The most important
      adverse outcome associated with IUD use is higher rates of pelvic inflammatory
      disease; careful attention to proper insertion techniques can reduce this risk
      substantially, and LNg IUDs may cause no increase in risk. IUDs, like both
      sterilization and Norplant, provide no protection against sexually transmitted
      disease. The TCu380A IUD is extremely cost-effective. There is as yet no public
      sector price for the LNg IUD, which has not been approved by the U.S. Food and
      Drug Administration and is not provided by family planning donor organizations.
      If it can be made available to the public sector at a price substantially less
      than its present market price, the LNg IUD would be a useful addition to the
      contraceptive armamentarium for developing countries. CONCLUSION: Providers,
      consumers and family planning program managers should begin to see IUDs as
      potential substitutes for both surgical sterilization and Norplant.

PMID- 10202747
TI  - Using amino-cerv after cervical LEEP.
AB  - OBJECTIVE: To evaluate the ability of Amino-Cerv to promote healing of the cervix
      following loop electrical excision procedure (LEEP) of the cervix for cervical
      intraepithelial neoplasia. STUDY DESIGN: A randomized study was conducted on 48
      women in a private office setting. Patients were divided into two groups, to use
      or not use Amino-Cerv intravaginally for two weeks after the procedure.
      Statistical analysis of the findings were performed using the chi 2 test.
      RESULTS: Twenty of 24 (83%) of women using Amino-Cerv had completely healed
      tissue at four weeks, whereas 12 of 24 (50%) in the untreated group had healed
      tissue at four weeks. Findings were not statistically significant at two weeks
      but were statistically significant (P < .005, power = .55) at four weeks after
      the procedure. CONCLUSION: Amino-Cerv after LEEP of the cervix promotes healing.

PMID- 10202748
TI  - Ovarian tumors complicating pregnancy. Emergency and elective surgery.
AB  - OBJECTIVE: To retrospectively evaluate the different effects and characteristics
      of ovarian surgery performed under emergency conditions and electively during
      pregnancy and to search for risk factors contributing to emergency ovarian
      surgery. STUDY DESIGN: Between 1980 and 1996, 174 patients undergoing adnexal
      surgery during pregnancy or the puerperium were reviewed at Veterans General
      Hospital-Taipei. Of these 174 patients, 32 underwent emergency surgery (group A),
      while 142 patients underwent elective surgery (group B). In order to search for
      differences between the emergency and elective operations, patients in both
      groups were analyzed, with particular emphasis on the characteristics and outcome
      of pregnancy. RESULTS: In contrast to elective operations, there were five
      distinct aspects of emergency surgery. First, half of them occurred in the first
      trimester. Second, they contributed to 75% (9/12) of the total fetal wastage and
      85.7% (6/7) of spontaneous fetal loss (P = .00016). Third, tumor sizes (11.1 +/-
      4.2 cm) were significantly larger than those found (8.3 +/- 3.76 cm) in the
      elective surgery group (P < .05). Fourth, tumors less than 5 cm never caused
      symptoms requiring surgery. Fifth, an increasing incidence of completely
      extirpative surgery and general anesthesia was noted (P < .005). Incidence of
      tumors greater than 10 cm during pregnancy increased with malignancy (P = .0295)
      and before emergency surgery (P = .00001). CONCLUSION: We could remove ovarian
      tumors greater than 10 cm in diameter or with a teratoma component at earlier
      stages of pregnancy (after the seventh week of gestation) to avoid unpredictable
      complications. This reduces the risks of malignancy and emergency surgery. There
      was no evidence of increasing risk of fetal loss when surgery was performed after
      the seventh week of gestation.

PMID- 10202749
TI  - Impact of lifestyle choices on female infertility.
AB  - OBJECTIVE: To inform physicians who are involved in the primary care of
      reproductive-age women of the specific relationships between lifestyle choices
      and infertility so that they can use this knowledge to educate their patients and
      encourage changes in behavior. STUDY DESIGN: A review of the relevant literature,
      performed via Medline search. RESULTS: Prevention of chlamydial and gonorrheal
      infections; maintenance of the proper body weight; increased individual awareness
      about the effects of age on fecundity; and reduced intake of caffeine, tobacco
      and alcohol are all possible avenues for primary prevention of infertility.
      CONCLUSION: Lifestyle choices can be made that influence the reproductive
      capability of women. It may be worthwhile for primary care physicians to use
      information on lifestyle to encourage their patients to improve their overall
      health while positively affecting their ability to reproduce.

PMID- 10202750
TI  - Enterovesical fistula complicating pregnancy. A case report.
AB  - BACKGROUND: Enterovesical fistula is a rare cause of recurrent urinary tract
      infections. This condition is unusual in young people as common etiologies
      include diverticular disease and cancer. When an enterovesical fistula occurs in
      women of childbearing age, Crohn's disease is a likely cause. To our knowledge,
      enterovesical fistula complicating pregnancy has not been reported before. CASE:
      A pregnant woman with recurrent urinary tract infections was evaluated.
      Cystoscopy was suggestive of an enterovesical fistula, which was confirmed by
      charcoaluria following oral charcoal administration. The prenatal course was
      complicated by two episodes of hemorrhagic cystitis despite antibiotic
      prophylaxis. The patient had an uncomplicated term spontaneous vaginal delivery.
      An upper gastrointestinal series performed postpartum was suggestive of Crohn's
      disease and confirmed an enterovesical fistula. Surgical repair was successfully
      performed three months following delivery, revealing Crohn's disease. CONCLUSION:
      Enterovesical fistula may be an unusual cause of recurrent urinary tract
      infections in pregnancy. In this case, enterovesical fistula was the presenting
      symptom of Crohn's disease.

PMID- 10202751
TI  - Endometrial fluid collection in women with PCOS undergoing ovarian stimulation
      for IVF. A report of four cases.
AB  - BACKGROUND: The presence of endometrial fluid collections' developing during
      ovarian-stimulation was previously reported to occur in women with hydrosalpinx.
      We report on the occurrence of endometrial fluid collections in four women with
      polycystic ovary syndrome (PCOS) undergoing ovarian stimulation for in vitro
      fertilization. CASES: Four women developed endometrial fluid collections during
      ovarian stimulation. These fluid collections were noted as early as day 5 of
      stimulation. The reproductive outcome when fluid collections were noted on the
      day of human chorionic gonadotropin (hCG) or of embryo transfer (ET) was poor.
      One of three women with fluid collection on the day of hCG conceived but had a
      missed abortion. One patient with fluid on the day of ET failed to conceive.
      Three of four patients who underwent repeat cycles conceived when no fluid
      collections were seen on day of hCG or ET. CONCLUSION: Abnormal endometrial
      milieu could be an underlying defect in some women with PCOS and chronic
      anovulation who fail to conceive with ovulation-induction agents. This is the
      first report of endometrial fluid collections in patients with PCOS in the
      absence of hydrosalpinx. Continuous monitoring of the endometrial lining during
      ovulation induction is mandatory to rule out any abnormality in endometrial
      development. Cryopreserving all embryos may be considering in cycles with fluid
      collections noted on the day hCG or ET.

PMID- 10202752
TI  - Prenatal diagnosis of dyssegmental dysplasia. A case report.
AB  - BACKGROUND: Since the first use of sonography, most fetal dwarfism has been
      detectable prenatally. The correct differentiation of the subtype of dwarfism is
      difficult at times. Dyssegmental dysplasia is probably an exception to these
      subtypes because the vertebral disorganization and occipital encephalocele at
      times permits prenatal diagnosis. CASE: A 34-year-old woman, gravida 3, para 1,
      elective abortion 1 for dwarfism, was referred at 27 weeks' gestation for cystic
      hygroma. Further sonographic findings included: cystic hygroma with massive
      ascites, micromelia, occipital encephalocele, spinal disorganization and
      hydramnios. The fetus and both parents appeared to have a normal karyotype. Later
      the pregnancy was terminated with vaginal delivery. The fetus had micromelia,
      camptomelia, cystic hygroma, a flat face, short neck, short trunk, narrow thorax
      with protuberant abdomen, scoliosis and clubfeet. CONCLUSION: Sonography is
      effective in prenatal diagnosis of dyssegmental dysplasia. With sonography,
      diagnosis of dyssegmental dysplasia becomes possible as early as the first
      trimester.

PMID- 10202753
TI  - Cervical sarcoma botryoides. A case report.
AB  - BACKGROUND: Sarcoma botryoides is a rare gynecologic malignancy. Reported
      treatment protocols range from localized resection of the tumor to radical
      surgery and adjuvant chemotherapy. Recently, limited excisional surgery combined
      with chemotherapy has contributed to excellent survival rates and preserved
      bladder and rectal function. CASE: We report a case of cervical sarcoma
      botryoides with minimal invasion. The patient had primary surgical treatment with
      complete resection of the tumor without adjuvant chemotherapy. Four months after
      surgery she presented with extensive metastatic retroperitoneal disease and died
      two weeks later. CONCLUSION: The clinical course of this patient suggests that
      complete surgical resection in cases of localized disease is not adequate therapy
      for sarcoma botryoides. Adjuvant chemotherapy should always be used, even at a
      very early stage.

PMID- 10202754
TI  - Decline in bone mineral density with stress fractures in a woman on depot
      medroxyprogesterone acetate. A case report.
AB  - BACKGROUND: Depot medroxyprogesterone acetate is a popular contraceptive among
      young, physically active women. However, its administration has been linked to a
      relative decrease in estrogen levels. Since bone resorption is accelerated during
      hypoestrogenic states, there has been growing concern about the potential
      development of osteoporosis and fractures with the use of this contraceptive
      method. CASE: A physically active, 33-year-old woman demonstrated a 12.4% drop in
      femoral neck bone mineral density (BMD), 6.4% drop in lumbar BMD and 0.8% drop in
      total BMD with the subsequent development of a tibial stress fracture while on
      depot medroxyprogesterone acetate. Bone mineralization rapidly improved, and the
      stress fracture resolved with discontinuation of the medication. CONCLUSION: The
      long-term effects of depot medroxyprogesterone acetate on bone mineralization in
      physically active women should be evaluated more thoroughly.

PMID- 10202755
TI  - Preconception care in diabetic women.

PMID- 10202756
TI  - Colposcopic guidance for LOOP.

PMID- 10202757
TI  - Rudimentary uterine horn pregnancy.

PMID- 10202758
TI  - Lichen sclerosus and thyroid disease.

PMID- 10202760
TI  - [How do antipsychotics exert their effects on dopamine receptor subtypes?].
AB  - There have been many efforts to develop novel antipsychotic drugs with improved
      clinical efficacy and reduced side effects such as extrapyramidal side effects
      and hyperprolactinemia. Recent evidences from studies on the effects of novel
      antipsychotic drugs such as clozapine on neurotransmitter receptors are prompting
      reconsideration of the dopaminergic hypothesis of schizophrenia. This paper gives
      an overview of the current understanding, including our data, of the effects of
      several antipsychotics on dopamine receptor subtypes. The recent cloning of
      dopamine receptors has revealed that multiple dopamine receptor subtypes are
      generated from at least five distinct dopamine receptor genes. Aripiprazole, a
      candidate for a novel antipsychotic, has an antagonistic activity against
      dopamine D2 receptors with a high affinity, but has a weaker potency to up
      regulate D2 receptors than haloperidol in the striatum and inhibitory effects on
      D2-receptor binding activities and mRNA in the pituitary, when it is chronically
      administrated to rats. Thus the occupancy or influences in D2 receptors in the
      striatum are involved in the extrapyramidal side effects of typical antipsychotic
      drugs. These studies provide new leads to understand the pathophysiology and
      causes of schizophrenia and to develop more effective and safe methods of
      treatment.

PMID- 10202759
TI  - [Molecular and neuroanatomical mechanisms of sleep-wakefulness regulation by
      prostaglandins D2 and E2].
AB  - Prostaglandin (PG) s D2 and E2 are the major arachidonic acid metabolites in the
      mammalian brain. PGD synthase, the enzyme that produces PGD2 in the brain, is
      mainly localized in the arachnoid membrane and choroid plexus. It is secreted
      into the cerebrospinal fluid and circulates in the brain through the ventricular
      system. PGD2 induces sleep by acting on the surface of the ventro-medial region
      of the rostral basal forebrain, the signal of which is probably transmitted into
      the brain parenchyma by adenosine via adenosine A2a receptors. Fos expression
      experiments suggest that PGD2 inhibits histaminergic arousal neurons of the
      tuberomammillary nucleus (TMN) in the posterior hypothalamus by activating
      inhibitory neurons in the ventrolateral preoptic area (VLPO). However, PGE2
      causes wakefulness by activating arousal neurons in the TMN via AMPA type
      excitatory amino acid receptors. Therefore, PGD2, acting as a sleep-inducer, and
      PGE2, acting as a wakefulness-promoter, jointly regulate the generation of sleep
      and wakefulness in the mammalian brain.

PMID- 10202761
TI  - [Vocalization response used for evaluation of pain-related behavior in guinea
      pigs].
AB  - In general, pain has been defined as "an unpleasant sensory and emotional
      experience associated with actual or potential tissue damage, or described in
      terms of such damage", and hence pain is a subjective and emotional experience
      for each individual. For this reason, it is difficult to study pain in nonverbal
      animals. However, painful stimuli (noxious stimuli) can cause both a simple and
      an overt emotional behavior such as self-defense reaction and vocalization in
      animals. Therefore, we are able to measure these behaviors as nonverbal
      communication of pain. The vocalization responses is the natural nociceptive
      reaction of conscious animals and prelingual children. In the present overview,
      we described the methodology for objective assessment of guinea pig's
      vocalization response to arterial algogenics and its characteristics.

PMID- 10202762
TI  - [Effects of amrinone on renal blood flow and cardiac function, in comparison with
      those of milrinone and olprinone, in anesthetized dog].
AB  - Amrinone, one of the phosphodiesterase III inhibitors, is clinically used for
      acute heart failure and possesses diuretic action, which is not observed in other
      phosphodiesterase III inhibitors. To clarify the mechanism of the diuretic action
      of amrinone, we investigated its effects on renal blood flow and some other
      hemodynamic parameters in comparison with the effects of milrinone and olprinone
      in anesthetized dogs. Amrinone increased both renal and femoral blood flow in a
      dose-dependent manner. On the other hand, milrinone and olprinone increased only
      femoral blood flow and had no effect on renal blood flow. Amrinone, milrinone and
      olprinone dose-dependently increased left ventricular max dp/dt, and the
      estimated slope of the dose-response curve for olprinone was significantly
      sharper than that of amrinone. Furthermore, these three drugs increased the
      cardiac index and decreased systemic vascular resistance (SVR) significantly. The
      action of amrinone on SVR was more potent than those of milrinone and olprinone.
      These results suggest that the diuretic action of amrinone is involved in
      augmentation of renal blood flow and may support useful effects on acute heart
      failure.

PMID- 10202764
TI  - [An ergonomic study of the work sites of female tellers in a state savings bank].
AB  - The object of the present investigation was, on the basis of analysis of the
      activity of female cashiers in state saving bank (SSB), working with video
      display terminals (VDT), and of investigation the subjective complaints,
      evaluation of the ergonomic factors of the working places to be made, which could
      serve for the elaboration of adequate preventive measures. Inquiry and ergonomic
      methods, chronometric measurements and interviews were used. The investigations
      were performed on 66 female cashiers from 4 branches of SSB--Sofia. The analysis
      revealed that according to the different indices the working places did not meet
      the ergonomic requirements. The principal unfavourable ergonomic factors were the
      discrepancy of the illumination of the working places with the requirements of
      similar type of activity and the characteristics of the sitting posture. The
      cashiers estimated the illumination as insufficient with poor distribution of the
      lighting sources. The arrangement and principal parameters of the working places
      did not correspond to the recommended ones. Discrepancies as insufficient length
      and width of the working surface, insufficient space for the legs were causes for
      occupying non-ergonomic working postures and led to tension of the muscular
      skeletal system. About 2/3 of the examined female cashiers had complaints of
      pains in the neck, back and lumbar region, which they related to the occupied
      working posture and to the arrangement and dimensions of the working places.

PMID- 10202763
TI  - [Influence of T-593 on the recurrence and relapse of cryocautery-induced gastric
      ulcer in rats: sequential observation with an endoscope and histological
      evaluation].
AB  - We investigated the influence of T-593, a novel anti-ulcer agent, on the
      recurrence and relapse of cryocautery-induced gastric ulcer in rats, in
      comparison with the action of famotidine and ranitidine. The drugs were
      administered from the 7th to the 119th day and then discontinued to the 190th day
      after induction of gastric ulcer. The healing, recurrence and relapse process of
      gastric ulcer was sequentially observed with an endoscope. In the control group,
      the reduction of ulcer index was observed until the 76th day after ulcer
      induction followed by aggravation, suggesting the recurrence and relapse occurred
      on cryocautery-induced gastric ulcer in rats. In the famotidine and ranitidine
      groups, the recurrence and relapse occurred after cessation of administration.
      The recurrence and/or relapse rate of T-593 was lower than those of other drugs.
      In the histological measurement, the grades of heterotopic regenerated gland and
      inflammatory cell infiltration of T-593 was lower than those of the control and
      other drugs in the ulcer area. From these results, it is concluded that T-593
      induces ulcer healing with a lower recurrence and/or relapse rate of ulcers than
      other conventional H2-antagonists, and T-593 may thus be a useful anti-ulcer drug
      for clinical therapy.

PMID- 10202765
TI  - [Occupational sensitization to methylene diphenyl diisocyanate during the
      manufacture of polyurethane products].
AB  - A complex occupational hygienic and clinical allergologic investigation in a
      methylene-diphenyl diizocyanate (MDI)-based polyurethane products manufacture was
      carried out for the first time in this country. The average MDI concentrations
      for a shift are within the limits of TWA, but during short operations exceed STEL
      and reach 0.072-0.181 mg/m3. By clinical and immuno-allergologic methods, applied
      on 46 MDI-exposed workers and 42 controls, the sensibilizing effect on the
      respiratory system, skin and eyes was detected. The allergic reactions take the
      course of bronchial asthma (6.5%), rhinitis and rhinopharyngitis (37%),
      rhinosinusitis (13%), conjunctivitis (13%), and urticaria and dermatitis (17.4%),
      as in 12 cases (12%) the allergic illnesses are combined. The specific
      occupational sensibilization, proved by positive dermal allergy tests with MDI in
      24 (52%) exposed workers, and increased MDI-IgE antibodies in 4 workers, is of
      high statistical reliability in comparison with the control group and supposes
      immune reactions of quick type (IgE) and mainly retarded type--cell mediated.
      Various prophylactic measures against the proven occupational sensibilization
      risk are proposed.

PMID- 10202766
TI  - [An experimental study of a microbiological index in the complex setting of
      standards for lead, copper and zinc in the soil].
AB  - Anthropological pollutions falling in the soil by different routes evolve
      multitude unfavourable consequences for human being and health. The present
      publication considers a laboratory survey on the influence of lead, copper and
      zinc by their combined presence in soil onto soil autocleaning ability. The
      results from the experiments will serve the goals of complex hygiene standards of
      these three soil pollutants. A number of micro-organisms, relating to soil as an
      ecological compartment, are tested by two hygienic microbiological methods. The
      results from experiments point out as maximum permissible concentration (MPC) the
      following combination of concentrations within the range of the microbiological
      index: lead--54 mg/kg, copper--90 mg/kg, zinc--165 mg/kg. Concentrations over the
      above-mentioned have an oppressive effect on saprophytic microflora in higher
      rate than the observed impact of pathogenic micro-organisms. In conditions of MPC
      higher than the reached ones the autocleaning ability of the soil is threatened
      and thus a basis with unfavourable epidemiological indicators is established.

PMID- 10202767
TI  - [The observation and assessment of air pollution in the region of the city of
      Silistra].
AB  - In the region of the town of Silistra there are no big industrial enterprises,
      sources of harmful emissions in the surroundings. After the starting in
      exploitation of the Metallurgical Works in Calarasi [correction of Kalarash] in
      1987 began the complaints of the population as result of episodic pollutions of
      the atmospheric air in the region. Productions of similar character emit in the
      atmosphere dust, sulfur dioxide, carbonic oxide, nitric oxides, hydrogen sulfide,
      fluorides, ammonia, pyridine, aromatic and polyaromatic carbohydrates, phenol and
      aerosols of heavy metals. For this purpose on the territory of the town of
      Silistra two stationary stations of HEI are functioning for systemic observation
      and evaluation of the atmospheric pollution for the indices: dust, sulfur
      dioxide, nitric dioxide, hydrogen sulfide, phenol and aerosols of heavy metals.
      All data are statistically processed by means of statistical programme packet
      "STATGRAPH".

PMID- 10202768
TI  - [The neurobehavioral effects of solvents].
AB  - The paper correlates basic literature on the neuropsychological consequences and
      a wide range of organic solvents, which are known to induce disorders that range
      from a "neurasthenic-like" psychological disorders to dementia. By highlighting
      the type of impairments that are most likely to be associated with organic
      solvents and their mixtures human neurotoxic solvent syndromes are identified and
      assessed. The paper provides with a briefly description of classes of solvents,
      their common characteristics, routes of solvent exposure and general toxic
      effects. General assessment strategies as well as specific neuropsychological
      procedures and diagnostic criteria are discussed. The confounding of
      neuropsychological evaluation with individual characteristics, attitudes and life
      style, psychosocial and medical disturbances and group dynamic processes that
      hamper the correct causal attribution of exposure effects is considered.

PMID- 10202769
TI  - [Lipid peroxidation in chronic lead exposure].
AB  - The state of lipid peroxidation, monitored by MDA concentration in the blood
      plasma of 46 battery workers with lead level in the blood in the 1.26-5.6 mol/l
      range is investigated. Higher MDA concentration (4.61 + 0.6) mol (ml in the blood
      plasma of exposed workers in comparison with the control sample of nonexposed
      workers is statistically established. The greater part of exposes workers (56.6%)
      have MDA concentration above the upper reference range. The significant
      correlation (r = +0.54) of the lipid peroxidation with the lead level in the
      blood is established. The investigation results show the rise of lipid
      peroxidation in workers chronically exposed to lead. This rise is more
      significant at lead levels above 1.92 mol/l.

PMID- 10202770
TI  - [The effect of the zinc-containing preparation Oxyrich in the treatment of
      chronic saturnism (preliminary results)].
AB  - Under indoor conditions the effect of the Bulgarian zinc-containing preparation
      Oxyrich was studied in the treatment of 12 workers (males) with chronic
      saturnism. The preparation was orally administered in a dose of 150 mg (0.45 mmol
      Zn++) daily for 10 days in three equal receivings, after which three day
      antidotal therapy with CaNa2 EDTA was carried out according to the classic
      schedule. The complex investigation of the workers besides the clinical
      exmination included some key indices of the porphirine metabolism (5-ALK-D, 5
      ALK, free protoporphirine in the red bolld cells), as well as the content of zinc
      and lead in the blood and their excretion with the urine prior and post the
      administration of Oxyrich and CaNa2 EDTA. The results of the carried out study
      revealed that the therapy with Oxyrich demonstrated a tendency to normalization
      of the activity of 5-ALK-D and decrease of the elimination of 5-ALK. This gave
      grounds for further study with higher doses of Oxyrich, as well as enlargement of
      the spectrum of the indices of the porphirine metabolism.

PMID- 10202771
TI  - [Tylosin-specific proliferation in vitro of the peripheral blood mononuclear
      cells in occupational tylosin allergy].
AB  - Tylosin-specific lymphocyte proliferation in vitro and its restriction of HLA
      class II antigens have been investigated in 21 allergic workers exposed to
      tylosin. Nine workers from tylosin industry without allergic symptoms and five
      nonexposed nonallergic subjects served as controls. The results showed a
      significantly higher lymphocyte proliferative response to tylosin in allergic
      workers compared to control groups. Lymphocyte proliferation was observed in five
      workers with allergic complaints but negative skin tests. The tylosin
      concentration leading to maximal proliferative response varied from 10 to 1000
      micrograms/ml among individuals. Six from seven workers with maximal response to
      the lowest concentration of tylosin carried HLA-DQ2 antigen. Lymphocyte from most
      control subjects did not respond in vitro to tylosin. Weak proliferative response
      to tylosin was observed in two workers without clinical symptoms of allergy. No
      association was found between lymphocyte reactivity to PHA and tylosin in the
      three studied groups. In conclusion, tylosin leads to a specific activation of T
      lymphocytes in occupationally sensitized workers. Possibly, the T cell
      recognition of the hapten/protein complex is restricted by HLA-DQ2 antigen in
      tylosin occupational allergy. Lymphocyte stimulation test can be used for the
      diagnosis of tylosin occupational allergy, as well as for the detection of
      latently sensitized workers.

PMID- 10202772
TI  - [An evaluation of the toxic exposure to inhalation anesthetics and disinfectants
      on liver function. II].
AB  - The object of the study was evaluation of the functional state of the liver of
      surgeons and anaesthesiologists, exposed to halothane, paradise gas and
      disinfectants (formaldehyde). A representative group of 107 individuals was
      involved, distributed into two professional groups: surgeons (AcAT, AIAT, AP,
      gamma-GT) was determined. The analyses were performed on "Pointe 190", USA.
      Increased incidence and degree of deviations in the transaminases were
      established; a correlation between the results from the biochemical analyses and
      the toxicometric records. In conclusion the established correlations "dose
      effect" and "dose-response" confirmed that the liver is a critical organ under
      the conditions of combined effect exerted by haolthane and paradise gas.

PMID- 10202773
TI  - [Deviations in the hematological indices of women exposed to aromatic
      hydrocarbons].
AB  - The indices of peripheral blood were investigated in 73 female laboratorians of
      the "Complex Laboratory for Analysis of Aromatic Carbohydrates", who were
      distributed into four groups according to the intensity of exposition. In the air
      of the laboratory medium the following substances were determined: benzene,
      toluen, xylols, ethylenic oxide, acrylnitril. The established concentrations were
      below or around the values of the mean maximum admissible concentrations (MMACV).
      Eleven indices of the three blood populations were followed up including white
      blood cell differential count and assessment of the activity of alkaline
      phosphatase in the polymorphonuclears. The same indices were investigated in 22
      females, forming a control group. It was established that 26% of the examined
      female laboratorians were with anaemic syndrome, in 22.8% leucocytosis was
      present, while the alkaline phosphatase in the polymorphonuclears was with
      strongly inhibited activity. Although that on the bases of the formed 4 groups
      the dependencies "dose-response" and "dose-effect" were not established, the
      described deviations in the indices of the peripheral blood and expressed in a
      high percentage of the female laboratorians of the "Complex Laboratory for
      Analysis of Aromatic Carbohydrates" (CLAAC) direct to exerted effect by the
      occupational chemical harms upon the blood system of the examined females.

PMID- 10202774
TI  - [The role of nitrates in the genesis of goiter morbidity].
AB  - Epidemiologic study was carried out concerning the level of goitrous morbidity in
      the growing up individuals aged from 3 to 14 years, permanently living in a
      settlement with increased nitrate content in the drinking water and natural
      Iodine deficiency. The data for the incidence of the goitrous morbidity were
      compared with those of a control group of children. The investigation included a
      total of 325 children. A high percentage of goitrous morbidity was recorded in
      the observed by us settlement with increased nitrate content in the drinking
      water, respectfully 35% versus 8.1% in the control settlement. Low degree of
      juvenile goiter predominated with slight prevalence of the female sex. A
      statistically reliable difference (p < 0.001) in the incidence of goitrous
      morbidity in the observed by us settlement and the control settlement.

PMID- 10202775
TI  - [The memorization of new material and the probable energy processes in the short
      term and long-term memories of adolescents].
AB  - In age-related, occupational and individual aspects the dynamics of the
      transition of the visual technical information was investigated from short-term
      to long-term memory in growing up individuals, mastering the profession of
      operator-power engineer. The variants of probable distribution of the nervous
      energy between focus and background of the operative field of the brain were
      considered in the examined pupils. It was established that at the first
      presentation of complex technical information the occupationally adapted pupils
      in significant higher volume were able to assimilate the presented information
      than the occupationally unadapted ones. It was demonstrated that the process of
      transition of the visual information from conditions of short-term to long-term
      memory processed by stages in all examined individuals according to the
      assimilation or loss of part of the presented for memorizing information in every
      cycle of its repetition. It was assumed that each stage of memorizing which is
      connected with assimilation or loss of the information had its connected with
      assimilation or loss of the information had its strictly individual energetic
      characteristics. The complex variants of the energetic processes were considered.
      The results of the carried out investigations also revealed that assimilation of
      visual information depended to a greater extent of the individual abilities of
      the pupils rather than of their age.

PMID- 10202776
TI  - [The physical development of children living in a settlement with a high nitrate
      content in the drinking water].
AB  - The object of the present study is analysis of the physical development of
      children, living permanently in the village of Karadzhalovo, community of
      Parvomay, whose drinking water contains abnormal concentration of nitrates. For
      the period 1983-1994 the nitrate content in the drinking water of the village
      varies within the limits of 67.0 to 112.6 mg/dm3. Complex evaluation of the
      physical development of 162 children aged from 3 to 16 years was carried out on
      the indices level of development of stature and degree of harmony of the body
      mass. The data were compared with the norms for physical development of the
      Bulgarian children. 90.4% of the boys and 86.8% of the girls are with good
      physical development. With satisfactory development are 8.5% of the boys and
      13.2% of the girls. Only 1.1% of the boys are with poor physical development,
      while among the girls there is no poor physical development. No reliable
      correlative dependency was established between the nitrate content of the
      drinking water and the stature and weight of the examined children.

PMID- 10202777
TI  - [The visual perception of the elements of technical drawings among masking
      distractions in advanced and nonadvanced students in the building and
      architectural professions].
AB  - To investigation were submitted the particularities of the process of visual
      perception of technical drawings and schemes in advanced and backward pupils, who
      were mastering the specialties of "building and architecture",
      "hydroconstruction", "transport construction", "geodesy". The time was
      registered, which was necessary to advanced and backward pupils for unveiling the
      different elements in the drawing, scheme, and such attributes of the drawing as:
      orientation, length, curves of the lined, the boundary between them; time for
      identification of the specific designations, symbols, group of symbols, elements
      of the sketch from the simple to the complex ones. The results of the
      investigations revealed that in the advanced pupils the perception (unveiling) of
      the different elements of the technical drawing proceeded very rapidly, almost
      automatically. In the backward pupils this process elapsed reliably more slowly.
      It was demonstrated that the growing up pupils, who were distinguished with more
      rapid perception of the different elements of the drawing (advanced ones) more
      rapidly and more exactly dealt with solution of the technical tasks as compared
      with these, who more slowly unveiled the looked for elements (backwardness). Some
      other individual particularities were also established with respect to the visual
      perception of the elements of the technical drawing and its properties in
      advanced and backward pupils who were mastering the investigated professions.

PMID- 10202778
TI  - [The health and hygiene problems of motor activity in childhood and adolescence].
AB  - Our investigations during the last decades emphasized the ever more increasing
      importance of the motor activity for the wholesome development of the child's and
      adolescent's body. Contrary to that, nowadays a tendency imposes for ever more
      immobile manner of life among the children and the growing up adolescents, which
      bears an extremely unfavourable influence on their physical development and
      activity, health conditions, as well as on a number of psycho-functional indices
      for their vital activity. The presented literary review from 36 origins
      demonstrate that as a result of hypokinesis the percentage of children and
      adolescent with overweight and obesity increases, the alimentary-energetic
      balance of the body is disturbed, the morbidity increases, particularly of the
      cardio-circulatory system, etc. All these phenomena impose in front of the
      physicians a number of health-hygienic problems, the solution of which could be
      achieved mainly by direction of the efforts for creation of adequate programmes
      for stimulation of the physical activity of the children and adolescents in the
      school, as well as in the family medium. The researchers in a number of highly
      developed countries even alarm for the constitution of national programmes for
      physical activity and physical education in view of saving the growing up
      generation from the noxious effect of hypokinesis with all deriving from it
      unfavourable for the health consequences.

PMID- 10202779
TI  - The role of religious and spiritual beliefs in coping with malignant melanoma.
AB  - This study investigated the role of spiritual and religious beliefs in ambulatory
      patients coping with malignant melanoma. One-hundred and seventeen patients with
      melanoma being seen in an outpatient clinic completed a battery of measurements
      including the newly validated Systems of Belief Inventory (SBI-54). No
      correlation was found between SBI-54 scores and levels of distress. However,
      there was a correlation between greater reliance on spiritual and religious
      beliefs and use of an active-cognitive coping style (r = 0.46, p < 0.0001). Data
      suggest that use of religious and spiritual beliefs is associated with an active
      rather than passive form of coping. We suggest that such beliefs provide a
      helpful active-cognitive framework for many individuals from which to face the
      existential crises of life-threatening illness.

PMID- 10202780
TI  - The role of religious and spiritual beliefs in coping with malignant melanoma: an
      Israeli sample.
AB  - This preliminary study examined the possible relationship between a newly
      developed instrument, the Spiritual Beliefs Inventory (SBI-54), and the coping
      style of a group of cancer patients in Israel. The sample consisted of 100
      malignant melanoma patients diagnosed at stages I and II, A and B. Patients were
      individually interviewed at home and completed seven self-reports. The present
      report focuses on the relationship of the SBI-54 with other measures of coping,
      psychological distress and social support. Findings showed that there was a
      significantly positive correlation between the SBI-54 and the active-cognitive
      coping style (r = 0.48, p < 0.01).

PMID- 10202781
TI  - Cancer experiences of African-American women as portrayed in popular mass
      magazines.
AB  - Popular magazines provide opportunities for teachable moments about cancer
      prevention and control to broad segments of the population. The purpose of this
      study was to evaluate attitudes and beliefs about cancer as presented in magazine
      cancer stories with a predominant readership of African-American women.
      Information was collected on full length cancer stories in Jet, Ebony and Essence
      from 1987 to 1995. There were 11 personal stories about cancer impact on women in
      the magazine issues over 9 years. Five themes emerged: religiosity, cancer
      fatalism, quality of life after diagnosis, interactions with medical personnel,
      and treatment choices. Within each theme area, specific subthemes were
      identified. Within religiosity, subthemes included the importance of faith, God's
      role, and the challenge to the spirit of a cancer diagnosis. Negative
      interactions with the medical system were described in 45% (5/11) of the stories.
      Quality of life emerged as an important issue in the cancer stories with death
      and dying, and pain or side-effects of treatment appearing in 64% (7/11) of the
      narratives. These results suggest that narratives in magazines with predominant
      readership among African-American women emphasize religious beliefs in cancer
      survival and present mixed attitudes towards European-American medical
      institutions. Mass media contributes to that discourse which shapes women's
      attitudes about survival from cancer.

PMID- 10202782
TI  - Borderline personality disorder and bone marrow transplantation: ethical
      considerations and review.
AB  - Bone marrow transplantation (BMT) is rapidly becoming a part of conventional
      cancer treatment. However, it remains a 'last-ditch' treatment option for
      patients who have exhausted other treatment modalities. Patients experience a
      significant amount of emotional distress during all stages of the BMT process.
      Patients with personality disorders experience even more emotional distress than
      average and their behavior is often detrimental to effective patient-staff
      interactions. A case of a borderline patient is presented with a discussion of
      the ethical issues involved in the evaluation of these patients and the
      determination of their appropriateness for transplant.

PMID- 10202783
TI  - Psychosocial aspects of haematopoietic stem cell donation for allogeneic
      transplantation: how family donors cope with this experience.
AB  - Peripheral blood stem cell (PBSC) allogeneic transplantation is an innovative
      medical procedure which has many advantages in comparison with bone marrow (BM)
      transplantation, but it involves administering haematopoietic growth factors
      (HGFs) to donors, the long-term physiological effects of which have not yet been
      established. The main aim of the present study was to analyse how family PBSC
      donors cope when confronted with this particular risk context. In addition to
      data collected on the personal and social aspects of the donors' experience,
      questionnaires were used to measure their quality of life (pain and anxiety)
      before, during and after donation, and they were subsequently interviewed in
      depth by a psychologist. Twenty-two donors participated in this study. They did
      not all react to the experience of blood cell donation in the same way, in terms
      of their own personal feelings, attitudes towards the donation, their
      relationships with the other members of the family, and their awareness of the
      risk involved.

PMID- 10202784
TI  - Assessment of quality of life during intensive chemotherapy or bone marrow
      transplantation.
AB  - Quality of life (QOL) of 179 patients with hematological malignancies,
      hospitalized for induction chemotherapy, allogeneic or autologous bone marrow
      transplantation (BMT), was analyzed on three time points at 10 days interval
      after completion of the cytotoxic treatment. The instruments used were the EORTC
      questionnaire--with modifications of the physical and social functioning
      subscales, in order to adapt to the prolonged stay in the hospital--, the
      Hospital Anxiety and Depression Scale, and a specifically designed leukemia/BMT
      module. The psychometric properties of the scales were confirmed, except for the
      physical functioning and social subscales, for which further methodological
      studies are warranted. A relatively high frequency of somatic symptoms, fatigue,
      anxiety and depression was observed, with a trend to improvement at the end of
      hospitalization. The overall self-assessed QOL correlated mainly with fatigue and
      emotional disorders but not with the somatic symptoms. Randomized disclosure of
      the collected information to the staff allowed them to better identify patients
      who needed a psychotherapeutic intervention, but did not influence the
      psychological and QOL outcomes.

PMID- 10202787
TI  - [UOEH and the future of occupational health].

PMID- 10202785
TI  - Psychological response to long-term group therapy: a randomized trial with
      metastatic breast cancer patients.
AB  - Research has demonstrated that short-term psychological interventions improve the
      quality of life of cancer patients. However, there is much less evidence for the
      efficacy of long-term interventions. We report the psychometric results from a
      randomized clinical trial (n = 66) assessing the effects of an 8 month, weekly
      psychological intervention on 30 metastatic breast cancer patients. Subjects were
      assessed at baseline, 4, 8 and 14 months for mood, quality of life and adjustment
      to cancer. Results demonstrated little psychometric difference between the
      control (n = 36) and intervention groups over this length of time, in spite of
      the fact that when the intervention subjects attended a weekend of support and
      training in coping skills, the usual significant, short-term changes were
      observed. In the long-term intervention, subjects did experience more anxious
      preoccupation and less helplessness than the controls but no recorded
      improvements in mood or quality of life. However, profound clinical changes were
      observed by the therapists, similar to those noted by Spiegel et al. (1981). We
      conclude that many of the psychological changes made by subjects in long-term
      interventions may elude conventional psychometric assessment. Further research,
      of a rigorous qualitative nature, is required to develop a clearer understanding
      of the experience of living and eventually dying of cancer within the context of
      a long-term intervention.

PMID- 10202786
TI  - [Institutional development of UOEH].

PMID- 10202788
TI  - Isokinetic strength of elbow extensor muscles correlates with race time in
      wheelchair half marathon racers.
AB  - It has been reported that grasping power and isometric muscle strength of elbow
      extensors in fine wheelchair racers were greater than the poor racers in the
      wheelchair full marathon. The purpose of the present study was to investigate the
      relationship between muscle strength of elbow extensors and flexors and the race
      time in wheelchair half marathon race. Four wheelchair half marathon racers who
      completed the half marathon division of the 16th Oita International Wheelchair
      Marathon (OIWM) in 1996 participated in the present study. The day before the
      race, all subjects reported to the training room and the isokinetic muscle
      strength of elbow extensor and flexor muscle groups was measured at angular
      speeds of 60 degrees, 120 degrees and 240 degrees/sec using the isokinetic
      dynamometer. There was a significant correlation between race time and isokinetic
      muscle strength of the elbow extensors at 60 degrees, 120 degrees and 240
      degrees/sec, but not flexor muscles. Our findings suggest that increased muscle
      strength of elbow extensors may improve the race time in wheelchair half marathon
      race.

PMID- 10202789
TI  - [Neurotoxicity of 1-bromopropane in rats].
AB  - Neurotoxicity of 1-bromopropane (1-BP) used as an alternative solvent of
      fluorocarbons was experimentally studied. Eight rats in the experimental group
      were exposed to 1-BP at 1500 ppm for six hours a day, five days a week for four
      weeks in an exposure chamber. Another eight rats in the control group were
      exposed to room air in a similar exposure chamber as those in the experimental
      group. During the latter half of the fourth week of exposure, all the rats in the
      experimental group showed a loss of body weight and ataxic gait compared with
      control rats. At the end of the fourth week, the rats in both groups were
      perfused through the ascending aorta and fixed. The cerebellum, medulla
      oblongata, spinal cord and peripheral nerve were processed for histopathological
      studies. No statistically significant difference in the frequency of axonal
      degeneration in both peroneal and sural nerves was found between the experimental
      and control groups. In the cerebellum, the frequency of degeneration of Purkinje
      cells in both the vermis and hemisphere was higher in the experimental group than
      in the control group (P < 0.05). There was no significant difference in the
      frequency of myelin ovoids in the fifth thoracic and in the third cervical
      posterior columns of the spinal cord between control and experimental groups.
      There was also no significant difference in the frequency of axonal swelling in
      the nucleus gracilis of the medulla oblongata between control and experimental
      groups. Ataxic gait was considered to be induced by degeneration of Purkinje
      cells in the cerebellum due to 1-BP exposure. However, degenerative findings of
      nerve fibers in the peripheral nerve, spinal posterior column and nucleus
      gracilis of the medulla oblongata due to 1-BP exposure were not evident. At the
      end of the fourth week of exposure, rats in the experimental group showed loss of
      body weight and markedly decreased motor activities, and it was considered that
      they would die if we continued the exposure into the fifth week. Therefore, we
      feel that our experimental schedule should be reconsidered before undertaking any
      further studies on the peripheral nerve toxicity of 1-BP.

PMID- 10202790
TI  - [Effect of benzene exposure on hematology and hepatic drug metabolic enzymes in
      ethanol administrated rats].
AB  - There are few reports regarding the effects of benzene and ethanol being
      administered simultaneously. In our experiments with 4 groups (controls, ethanol,
      benzene and ethanol plus benzene) Wistar male rats were treated with ethanol
      (20%) for 5 weeks, and then exposed to benzene (0.26 g/kg) for 5 days per week
      for 3 weeks. We also investigated the effects of benzene on the body weight,
      organ weight, peripheral hematology and hepatic drug metabolizing enzymes in the
      ethanol administrated rats. The liver weight increased significantly, but spleen
      weight decreased significantly in the benzene exposed group. Hematological
      examination showed a decrease of leukocyte in the two groups of benzene and
      ethanol plus benzene in comparison with the controls, but an effect promoted by
      ethanol was not found. Serum glutamate oxaloacetate transaminase (SGOT) and serum
      glutamate pyruvate transaminase (SGPT) values were not significantly different in
      the exposure groups when compared with the controls. The contents of microsomal
      cytochrome P450 in all the exposed groups showed a tendency to increase, but they
      were not significantly different in comparison with the controls. On the other
      hand, hepatic glutathione S-transferase activity in the exposed groups increased
      significantly.

PMID- 10202791
TI  - [A pivotal role of activated hepatic macrophage in the progression of alcoholic
      liver disease].
AB  - Our clinical and experimental research results indicated the possibility that gut
      derived endotoxin contributes to the development of alcoholic liver disease. Long
      term ethanol consumption resulted in an enhanced secretory function of hepatic
      macrophage accompanied by an ultrastructural feature of activation. The liver of
      rats fed on ethanol-diet were found to have an enhanced ability to produce CINC-1
      (rat IL-8) after endotoxin injection. This chemokine may contribute to neutrophil
      recruitment into the liver in alcoholic liver injury. Females exhibited a greater
      ability to produce CINC-1 than males, and this fact may account for the gender
      difference in susceptibility to alcohol-related liver disease.

PMID- 10202792
TI  - [Examination of dust generated from a workplace where steel wire coil are
      unwound].
AB  - Analyses of constituents, measurement of concentrations, research of size
      distributions and scanning electron microscopic examinations were carried out to
      determine the type and amount of dust generated in a working environment where
      steel wire coils are unwound. In about a 700 m2 work area unit, stationary
      samplings, including A-sampling (24 points) and B-sampling (1 point), which are
      defined by the law, were carried out. The dust concentration was measured by a
      digital dust indicator. A low volume air sampler was used to determine the
      conversion factor of the values obtained by the digital dust indicator. Because
      the result of the dust level by A-sampling and B-sampling were 0.64 mg/m3 and
      0.82 mg/m3 respectively, they can both be classified as Control Class 1. A
      proportion of less than 7 microns of the airborne dust made up about 15 to 20%
      (volume %) of the total dust in the working environments. Metallic dust and white
      dust were identified in the accumulated dust. By measuring with a X-ray
      diffractometry, it was determined that the metal dust constituent was Zn and the
      white dust constituent was Zn4CO3(OH)6.H2O. By a scanning electron microscopic
      examination, the scope of the particles was proven to be non-fibrous.

PMID- 10202793
TI  - Recent developments in diagnostic imaging of the gastrointestinal tract of the
      dog and cat.
AB  - The gastrointestinal (GI) tract comprises the esophagus, stomach, small
      intestine, large intestine, pancreas, mesentery, and associated lymph nodes.
      Diseases that result in structural lesions of the GI tract and diseases that
      cause abnormal GI motility are potentially detectable using diagnostic imaging
      techniques, whereas disorders of the GI tract that are manifested as histological
      lesions or metabolic dysfunction are not.

PMID- 10202794
TI  - Gastrointestinal pharmacology.
AB  - Treatment of diseases affecting the gastrointestinal tract often focuses on
      resolution of clinical pharmacology of drugs used to treat the gastrointestinal
      tract, starting with appetite stimulants, followed by emetics and antiemetics,
      and antidiarrheals. Prokinetic agents and drugs used for the treatment of
      gastroduodenal ulceration are also discussed. Discussions include mechanisms of
      drug action, disposition of drugs as it relates to therapeutic use, drug
      interactions, adverse drug reactions, and clinical indications.

PMID- 10202795
TI  - Diagnosis and treatment of gastric motility disorders.
AB  - A disorder of gastric motility should be suspected in patients with chronic
      vomiting. Imaging studies are used to confirm delayed gastric emptying, the most
      common form of a gastric motility disorder. Other causes of chronic vomiting, for
      example, metabolic or endocrine disorders, other abdominal disorders, mechanical
      causes of gastric obstruction, and lower gastrointestinal tract disease, are then
      ruled out. If no underlying cause is determined, a functional disorder of gastric
      emptying is presumptively diagnosed. Treatment consists of dietary management and
      gastric prokinetic agents. Cisapride is the drug of choice for treating delayed
      gastric emptying followed by erythromycin and ranitidine or nizatidine.

PMID- 10202796
TI  - Gastric Helicobacter infection in dogs.
AB  - Infection with gastric Helicobacter spp. is prevalent in dogs and is not
      accompanied by clinical signs in the majority of cases. Five different
      Helicobacter spp. have been found in the canine stomach. The modes of
      transmission are unclear, but fecal-oral, oral-oral, and surface water
      transmission are all possible. A diagnosis can be made using invasive or biopsy
      based tests, but noninvasive techniques using UBBT and serology hold promise for
      the future.

PMID- 10202797
TI  - Gastric neoplasia.
AB  - Gastric tumors are rare in dogs and cats but should always be considered,
      particularly in older dogs with chronic vomiting. The most common gastric tumor
      in dogs is carcinoma, although lymphoma is rare. Breeds that seem to be
      predisposed to gastric carcinoma are the Rough Collie, Staffordshire Terrier, and
      Belgian Shepherd. Lymphoma is the most common gastric malignancy in cats.
      Contrast radiographic examination and endoscopy are the elective procedures of
      choice for the diagnosis of these conditions. Biopsy is essential to confirm the
      diagnosis. Surgery is the only potentially curative modality for localized
      gastric carcinoma. Chemotherapy alone or following surgery is the elective
      treatment of choice for gastric lymphoma in dogs and cats. The prognosis is poor
      for both types of tumor, but prolonged survival times in individual animals are
      possible.

PMID- 10202798
TI  - Clinical laboratory evaluation of small intestinal function.
AB  - Although diarrhea as a consequence of dysfunction of the small intestine (SI) is
      a common presenting problem in practice, most cases are acute, nonfatal, and self
      limiting, and they require only symptomatic support. Thus, the need for any
      investigation of SI function beyond physical examination is a clinical judgment
      made on the potential of the problem being persistent, contagious, or life
      threatening. Acute, severe, or bloody diarrhea; concurrent signs of systemic
      illness; or chronic diarrhea (which is not self-limiting) indicate a need for
      more detailed investigations. In all cases, the fluid and electrolyte needs of
      the patient must be addressed even while the diagnostic effort is in progress.

PMID- 10202800
TI  - Inflammatory bowel disease. Current perspectives.
AB  - This review provides current perspectives on canine and feline (IBD) as
      documented in the literature. As can be seen, the scientific database on this
      clinical syndrome is minute. Empirical clinical observations and experiences are
      valuable but do not replace the "good science" that can be achieved by
      performance of basic science research studies and controlled therapeutic trials.
      Continued advances in immunobiology, particularly molecular biology, should
      facilitate a greater understanding of IBD in both humans and animals. Indeed,
      preliminary investigations using these research tools have provided new insights
      into the immunopathology of canine IBD.

PMID- 10202799
TI  - Gastrointestinal immunity in health and disease.
AB  - The gastrointestinal lymphoid tissue (GALT) is under constant antigenic challenge
      from bacteria and food and must be able to distinguish between benign and
      pathogenic organisms. Recent advances in understanding the organization and
      function of GALT reveal how it is able to direct appropriate immune responses
      according to the nature of the antigen and how inappropriate immune responses can
      lead to local and systemic immunopathology and/or infection. The interaction of
      the normal bowel flora and GALT is critical to normal local and systemic immune
      function and plays a major role in the pathogenesis of some immune-related
      diseases. This review draws upon information from veterinary, human, and
      laboratory animal studies to provide an update of mechanisms and consequences of
      function and dysfunction in the gastrointestinal immune system.

PMID- 10202801
TI  - Small intestinal bacterial overgrowth.
AB  - It is clear that the exact definition of small intestinal bacterial overgrowth
      (SIBO) needs to be reappraised in veterinary medicine. Antibiotic responsive
      enteropathies due to SIBO must be distinguished from those that are not
      associated with SIBO, such as those caused by a lack of immune tolerance. Once
      appropriate definitions and criteria for diagnosis are in place, the wide variety
      of diagnostic procedures that may facilitate the diagnosis can be evaluated with
      respect to their sensitivity and specificity, and statements about the prevalence
      and significance of this disorder can be made.

PMID- 10202802
TI  - Feline exocrine pancreatic disorders.
AB  - Despite the uncommon clinical diagnosis, cats frequently suffer from disorders of
      the exocrine pancreas. Pancreatitis is the most common feline exocrine pancreatic
      disorder. Pancreatitis can be acute or chronic and mild or severe. The etiology
      of most cases of feline pancreatitis is idiopathic. Some cases have been
      associated with severe abdominal trauma, infectious diseases, cholangiohepatitis,
      and organophosphate and other drug intoxication. The clinical presentation of
      cats with pancreatitis is nonspecific. Vomiting and signs of abdominal pain,
      which are the clinical signs most commonly observed in humans and dogs with
      pancreatitis, are only uncommonly observed in cats with pancreatitis. Routine
      laboratory findings are also nonspecific. Abdominal ultrasonography is a valuable
      diagnostic tool in feline patients with pancreatitis. Serum activities of lipase
      and amylase are rarely increased in cats with pancreatitis; however, these cats
      often have elevated serum fTLI concentrations. The goals of management are
      removal of the inciting cause, provision of supportive and symptomatic therapy,
      and careful monitoring for and aggressive treatment of systemic complications.
      Exocrine pancreatic insufficiency is a syndrome caused by insufficient synthesis
      of pancreatic digestive enzymes by the exocrine portion of the pancrease. The
      clinical signs most commonly reported are weight loss, loose and voluminous
      stools, and greasy soiling of the hair coat. Serum fTLI is subnormal in affected
      cats. Treatment of cats with EPI consists of enzyme supplementation with powdered
      pancreatic extracts or raw beef pancreas. Many cats with EPI have concurrent
      small intestinal disease. Most cats with EPI also have severely decreased serum
      cobalamin concentrations and may require parenteral cobalamin supplementation.
      Pancreatic adenocarcinoma is the most common neoplastic condition of the exocrine
      pancreas in the cat. At the time of diagnosis, the tumor has already metastasized
      in most cases, and the prognosis is poor. Pancreatic pseudocyst, pancreatic
      abscess, pancreatic parasites, pancreatic bladder, and nodular hyperplasia are
      other exocrine pancreatic disorders, that are less commonly seen in cats.

PMID- 10202803
TI  - Colonic fluid and electrolyte transport in health and disease.
AB  - A major function of the mammalian colon is the absorption of water and
      electrolytes from the luminal contents that enter through the ileocecal valve.
      The absorptive capacity of the colon is influenced by the rate of passage of the
      luminal contents. To maximize the efficiency of these processes, there is close
      coordination between motility and absorptive functions. A balance between the
      benefits of prolonged time of contact between the colonic mucosa and the luminal
      contents and the adverse effects of accumulated toxic and carcinogenic
      metabolites is essential.

PMID- 10202804
TI  - Pathogenesis, diagnosis, and therapy of feline idiopathic megacolon.
AB  - Many cats have one or two episodes of constipation without further recurrence,
      although others progress to complete colonic failure. Middle-aged male cats are
      particularly at risk for the clinical continuum of constipation, obstipation, and
      dilated megacolon. Pelvic canal stenosis and nerve injury are minor causes in the
      development of this syndrome. In most affected cats, the underlying pathogenesis
      appears to involve colonic smooth muscle dysfunction. In this group of cats, it
      is not yet clear whether this disorder represents a primary or secondary
      (resulting from long-standing constipation and colonic distension) abnormality.
      Many cats with mild to moderate constipation respond to conservative medical
      management (e.g., dietary fiber supplementation, emollient or hyperosmotic
      laxatives, colonic prokinetic agents). Indeed, early use of colonic prokinetic
      agents is likely to prevent the progression of constipation of obstipation and
      dilated megacolon in many cats. Some cats may become refractory to these
      therapies, however, as they progress through moderate or recurrent constipation
      to obstipation and dilated megacolon. These cats eventually require colectomy.
      Cats have a generally favorable prognosis for recovery following colectomy,
      although mild to moderate diarrhea may persist for 4 to 6 weeks postoperatively
      in some cases.

PMID- 10202805
TI  - Coping efforts in daily life: role of big five traits and problem appraisals.
AB  - The role of problem appraisal and Big Five traits in coping with bothersome daily
      events was investigated. Community-residing men completed diaries regarding
      stressful events and coping for eight consecutive days. Results of multi-level
      analyses indicated that lower perceived control over events was associated with
      greater reliance on distraction, catharsis, acceptance, seeking emotional social
      support, but less use of direct action. Stressor severity was positively
      associated with catharsis and religion, but negatively associated with
      acceptance. Neuroticism, Extraversion, Openness to experience, and
      Conscientiousness predicted coping strategy use. In addition, broad personality
      dimensions moderated relations between appraisals (perceived uncontrolability and
      severity) and coping strategy use. Although previous research implicated
      perceived control in coping, the present study suggests that both appraisals of
      stressor severity and individual differences in personality are also important
      determinants of coping strategy use at the daily level.

PMID- 10202807
TI  - Individual differences in emotional creativity: structure and correlates.
AB  - The structure and correlates of emotional creativity were explored in a series of
      six studies, using a specially constructed measure of individual differences--the
      Emotional Creativity Inventory (ECI). Analyses of the ECI suggest that three
      facets of emotional creativity can be distinguished empirically as well as
      theoretically, namely, preparedness (understanding and learning from one's own
      and others' emotions), novelty (the ability to experience unusual emotions), and
      effectiveness/authenticity (the skill to express emotions adroitly and honestly).
      Women score higher than men on emotional preparedness and
      effectiveness/authenticity, but not on the novelty of their responses. People who
      score high on the ECI are considered by their peers to be more emotionally
      creative, presumably on the basis of everyday behavior. Associations between
      emotional creativity as measured by the ECI and a variety of other personality
      variables (including the Big Five personality traits, mysticism, self-esteem,
      authoritarianism, locus of control, alexithymia, and ways of coping) are
      examined, as is the relation between emotional creativity and prior traumatic
      experiences.

PMID- 10202806
TI  - Identity consolidation in early adulthood: relations with ego-resiliency, the
      context of marriage, and personality change.
AB  - Identity consolidation during early adulthood was conceptualized as a process of
      investing oneself in new adult roles, responsibilities, and contexts and
      evaluating one's ongoing experience in order to construct a coherent, grounded,
      and positive identity. The current study longitudinally examined (age 21 to age
      27) the roles of ego-resiliency, an important personality resource, and marriage,
      an important identity context, in the process of identity consolidation as it
      unfolded in a cohort of women who experienced early adulthood during the early
      1960s. Prototypes of identity in marriage were developed to reflect the different
      ways these women invested and evaluated their identities in the context of
      marriage. Results showed that ego-resiliency at age 21 and the experience of
      identity in marriage at age 27 were both related to identity consolidation at age
      27, and findings also suggested that the relation of age 21 ego-resiliency to age
      27 identity consolidation was mediated by identity in marriage. Finally,
      successful identity consolidation was associated with increasing ego-resiliency
      from age 21 to age 27. Discussion focuses on the interaction between personality
      and social context in the process of identity consolidation and the role of
      identity consolidation in personality change.

PMID- 10202808
TI  - Shyness and sociotropy: additive and interactive relations in predicting
      interpersonal concerns.
AB  - Sociotropy (an aspect of interpersonal dependence) and sociability (affiliative
      need) were examined as moderator variables of the relationship between shyness
      and interpersonal concerns in two studies. In Study 1, sociotropy, but not
      sociability, predicted unique variance in three indices of interpersonal concerns
      through both direct and interactive relations with shyness. An initial analysis
      in Study 2 showed that sociotropy, but not sociability, was predictive of
      participants' perceived competence in situations that involved initiation of
      conversations and assertion. In the second part of Study 2, sociotropy accounted
      for significant increments in variance when predicting cognitive and affective
      manifestations of distress related to simulated conversation and assertion
      situations, while sociability did not. Study 2 results suggest that sociotropy
      operates primarily in an additive manner with shyness in predicting interpersonal
      concerns, rather than moderating the relation between shyness and interpersonal
      concerns. Differences in the results of the two studies and implications for
      future research are discussed.

PMID- 10202809
TI  - Endoxyloglucan transferase cDNA isolated from pea roots and its fluctuating
      expression in hydrotropically responding roots.
AB  - We isolated an endoxyloglucan transferase cDNA (Ps-EXGT1) from the roots of an
      agravitropic pea mutant, ageotropum. The putative product of the cDNA was 34.1
      kDa and consisted of 293 amino acid residues. The predicted amino acid sequence
      was 75.1-88.6% identical to those of EXGT genes in other plants. The Ps-EXGT1
      cDNA was strongly expressed in elongating roots and stems but not in either
      mature stems or young leaves. In roots, the transcription level of Ps-EXGT1 was
      most abundant in the rapidly growing region. When root elongation was inhibited
      by a water stress, Ps-EXGT1 transcription was repressed. The roots curved
      hydrotropically due to differential growth of the cortical cells in the
      elongation zone when the root cap was exposed to a gradient of water potential;
      the length of the cells on the side of lower water potential was much longer than
      those on the side of higher water potential. The expression pattern of Ps-EXGT1
      in the hydrotropically responding roots fluctuated between the side of the higher
      water potential and that of the lower water potential in the elongation zone. In
      other words, the accumulation of Ps-EXGT1 mRNA was much greater on the side of
      lower water potential than on that of higher potential just prior to the
      commencement of positive hydrotropism. When the roots started to curve slightly
      away from the side of higher water potential causing a rhythmic oscillatory
      movement [Takano et al. (1995) Planta 197: 410], there was more transcription of
      Ps-EXGT1 on the side of higher water potential. These results suggest that the
      transcription of Ps-EXGT1 is involved in cell growth and that this regulation of
      transcription plays a role in the differential growth of hydrotropically
      responding roots.

PMID- 10202810
TI  - Chloroplast NADH dehydrogenase from Pisum sativum: characterization of its
      activity and cloning of ndhK gene.
AB  - The pea chloroplast ndhK gene coding for a component of a NADH-plastoquinone
      oxidoreductase has been cloned and sequenced. This gene codes for a polypeptide
      of 227 amino acids and a predicted molecular mass of 25,495 Da which belongs to
      the family of the 20 kDa PSST subunit of the bovine mitochondrial complex I. A
      fragment of this gene has been overexpressed in Escherichia coli, and antibodies
      against the expressed polypeptide recognize a protein of the predicted molecular
      mass from pea thylakoid membranes. This polypeptide is a component of a protein
      complex with NADH dehydrogenase activity and is not associated with ferredoxin
      NADP+ reductase.

PMID- 10202811
TI  - Characterization of a palmitoyl-acyl carrier protein thioesterase (FatB1) in
      cotton.
AB  - The relatively high level of palmitic acid (22 mol%) in cotton seeds may be due
      in part to a palmitoyl-acyl carrier protein (ACP) thioesterase (PATE), which
      prefers C16:0-ACP as its substrate. In embryo extracts, PATE activity was highest
      at the maximum rate of reserve accumulation (oil and protein), occurring about 30
      35 d post anthesis. Thioesterase activity toward oleoyl-ACP was relatively
      similar at all developmental stages examined, but was considerably lower than the
      PATE activity. In developing seeds and in cotyledons and hypocotyls of seedlings,
      the PATE activity predominated. A cotton PATE cDNA clone isolated by screening a
      cDNA library with a heterologous Arabidopsis FatB1 probe has a 1.7-kb insert
      sequence with an open reading frame of 410 amino acids, lacking codons for the
      three N-terminal amino acids. The predicted amino acid sequence of the cotton
      PATE preprotein has a characteristic stromal-targeting domain and a 63% identity
      to the Arabidopsis long-chain acyl ACP-thioesterase FatB1 sequence. Alkaline blot
      hybridization of cotton genomic DNA with the Arabidopsis FatB1 probe suggested
      the presence of at least two FatB1 thioesterase genes in cotton. Relative cotton
      FatB1 transcript abundance was compared by RT-PCR and slot blot analysis in total
      RNA extracts from embryos, seedlings and leaves of mature plants. The cotton
      FatB1 mRNA apparently was expressed in all tissues but paralleled the profiles of
      PATE enzyme activity and seed oil accumulation in embryos.

PMID- 10202812
TI  - Expression characteristics of CS-ACS1, CS-ACS2 and CS-ACS3, three members of the
      1-aminocyclopropane-1-carboxylate synthase gene family in cucumber (Cucumis
      sativus L.) fruit under carbon dioxide stress.
AB  - We investigated the expression pattern of three 1-aminocyclopropane-1-carboxylate
      (ACC) synthase genes, CS-ACS1, CS-ACS2 and CS-ACS3 in cucumber (Cucumis sativus
      L.) fruit under CO2 stress. CO2 stress-induced ethylene production paralleled the
      accumulation of only CS-ACS1 transcripts which disappeared upon withdrawal of
      CO2. Cycloheximide inhibited the CO2 stress-induced ethylene production but
      superinduced the accumulation of CS-ACS1 transcript. At higher concentrations,
      cycloheximide also induced the accumulation of CS-ACS2 and CS-ACS3 transcripts.
      In the presence of CO2 and cycloheximide, the accumulation of CS-ACS2 transcript
      occurred within 1 h, disappeared after 3 h and increased greatly upon withdrawal
      of CO2. Inhibitors of protein kinase and types 1 and 2A protein phosphatases
      which inhibited and stimulated, respectively, CO2 stress-induced ethylene
      production had little effect on the expression of these genes. The results
      presented here identify CS-ACS1 as the main ACC synthase gene responsible for the
      increased ethylene biosynthesis in cucumber fruit under CO2 stress and suggest
      that this gene is a primary response gene and its expression is under negative
      control since it is expressed by treatment with cycloheximide. The results
      further suggest that the regulation of CO2 stress-induced ethylene biosynthesis
      by reversible protein phosphorylation does not result from enhanced ACC synthase
      transcription.

PMID- 10202813
TI  - Integrin-like proteins are localized to plasma membrane fractions, not plastids,
      in Arabidopsis.
AB  - Integrins are a large family of integral membrane proteins that function in
      signal transduction in animal systems. These proteins are conserved in
      vertebrates, invertebrates, and fungi. Evidence from previous research suggests
      that integrin-like proteins may be present in plants as well, and that these
      proteins may function in signal transduction during gravitropism. In past
      studies, researchers have used monoclonal and polyclonal antibodies to localize
      beta 1 integrin-like proteins in plants. However, there is a disparity between
      data collected from these studies, especially since molecular weights obtained
      from these investigations range from 55-120 kDa for integrin-like proteins. To
      date, a complete investigation which employs all three basic immunolabeling
      procedures, immunoblotting, immunofluorescence microscopy, and immunogold
      labeling, in addition to extensive fractionation and exhaustive controls, has
      been lacking. In this paper, we demonstrate that use of a polyclonal antibody
      against the cytoplasmic domain of avian beta 1-integrin can produce potential
      artifacts in immunolocalization studies. However, these problems can be
      eliminated through use of starchless mutants or proper specimen preparation prior
      to electrophoresis. We also show that this antibody, when applied within the
      described parameters and with careful controls, identifies a large (100 kDa)
      integrin-like protein that is localized to plasma membrane fractions in
      Arabidopsis.

PMID- 10202814
TI  - Abscisic acid-induced secretory proteins in suspension-cultured cells of winter
      wheat.
AB  - In suspension-cultured cells of winter wheat (Triticum aestivum L. cv.
      Chihokukomugi), the accumulation of soluble secretory proteins in the culture
      medium was promoted by ABA treatment in comparison with non-treated cells. The
      total amount of secretory proteins in ABA-treated cells was 1.7-fold higher than
      that in non-treated cells. The analysis of two-dimensional electrophoresis
      revealed that at least twelve secretory proteins were induced by ABA, and these
      were named WAS (wheat ABA-induced secretory) proteins 1 to 12. N-terminal amino
      acid sequence analysis of WAS proteins revealed the sequences of WAS-2 and WAS-3.
      Homology searches showed that WAS-2 had 55% identity with the N-terminus of the
      wheat chemically induced gene (WCI-5 gene) product. WAS-3 was also shown to have
      93% identity with the N-terminus of the barley protein R, a typical member of
      thaumatin-like proteins (TLPs). Immunoblot analysis also suggested that WAS-3 was
      related to protein R. These results suggest that exogenous ABA induces some basic
      secretory proteins that are related to the plant defense system in wheat.

PMID- 10202815
TI  - Identification and cDNA cloning of a protein abundantly expressed during apple
      fruit development.
AB  - A 60 kDa protein (MF-60) abundantly appearing in matured apple fruit was detected
      by SDS-PAGE of the soluble protein. It was partially purified through Butyl
      Toyopearl and DEAE-cellulose. Its partial amino acid sequences were determined to
      isolate a full-length cDNA. MF-60 cDNA (mf-60) consisting of 1,825 bp containing
      an open reading frame of 1,524 bp and encoding a 54.2 kDa polypeptide. The
      deduced polypeptide of mf-60 has 81.1% identity to turgor-responsive protein 26 g
      from wilted garden pea shoot. Northern blot and Western blot analyses showed that
      the levels of the protein and the transcript of MF-60 changed in parallel through
      the developmental season; they were very low in young fruit at 36 DAF and 60 DAF,
      started to increase at 85 DAF, and then remained at a higher level from 114 DAF
      to 176 DAF. These results suggested that MF-60 functions are connected with fruit
      development but not with the fruit ripening induced by ethylene.

PMID- 10202816
TI  - Two mRNA species encoding calcium-dependent protein kinases are differentially
      expressed in sexual organs of Marchantia polymorpha through alternative splicing.
AB  - In plants, calcium-dependent calmodulin-independent protein kinases (CDPKs) are
      the predominant calcium-regulated protein kinases and their genes are encoded by
      a multigene family. A CDPK gene was cloned from a liverwort, Marchantia
      polymorpha, which showed a high level of sequence similarities to other higher
      plant CDPK genes. The liverwort CDPK gene consisted of 9 exons and 8 introns. The
      6th and 7th exons (Exon 6A and Exon 6B) were almost identical except for 4-amino
      acid substitutions, both of which coded for EF-hands in the calcium-binding
      domain. RT-PCR analysis revealed that two species of mature mRNA containing
      either Exon 6A or Exon 6B were generated from a single CDPK gene by mutually
      exclusive alternative splicing. Both histidine-tagged fusion proteins derived
      from cDNAs containing either Exon 6A or Exon 6B exhibited calcium-dependent
      protein kinase activity in vitro. Preferential accumulation of the mature mRNA
      with Exon 6A detected in male sexual organ implies possible sexual control of the
      ratio between the two CDPK isozymes through alternative splicing. Functions and
      evolution of CDPKs are discussed based on the structure and expression of the
      liverwort CDPK gene.

PMID- 10202817
TI  - Auxin polar transport and flower formation in Arabidopsis thaliana transformed
      with indoleacetamide hydrolase (iaaH) gene.
AB  - Involvement of auxin polar transport in flower formation of Arabidopsis thaliana
      was studied using a pinformed (pin) mutant (Rpin) transformed with the
      indoleacetamide hydrolase (iaaH) gene and the phenocopy of the pin mutant, which
      was induced by 9-hydroxyfluorene-9-carboxylic acid (HFCA). The application of
      indoleacetamide (IAM) did not change aberrant structure of the aerial part of
      Rpin (pin/pin), but extremely inhibited its root growth. Treatment with IAM
      increased the endogenous concentrations of free and conjugated IAA in Rpin normal
      (pin/+ or +/+) due to the expression of the iaaH gene, to 140% and 428% of those
      in non-treated plants, respectively, and those in Rpin to 378% and 120%,
      respectively. The activity of IAA polar transport in the inflorescence axis of
      Rpin remained low even in the presence of IAM, the activity being almost similar,
      to that in the pin mutant. The activity of IAA polar transport in the HFCA
      induced phenocopy of the pin mutant was also extremely low, and it was not
      restored by the simultaneous application of IAA. Arabidopsis thaliana responded
      to HFCA applied from 7 to 11 d and from 25 to 29 d after germination in the wild
      type plant (Enkheim ecotype) and the late flowering mutant (fb mutant),
      respectively. These results suggest that the construction of the system of auxin
      polar transport and its normal activities are essential for the differentiation
      and the formation of floral meristem in the early growth stage of Arabidopsis
      thaliana.

PMID- 10202818
TI  - An adenylate cyclase, Cya1, regulates cell motility in the cyanobacterium
      Synechocystis sp. PCC 6803.
AB  - The cyanobacterium Synechocystis sp. PCC 6803 contained two genes, cya1 and cya2,
      encoding putative adenylate cyclases. The wild type cells are motile, whereas the
      disruption mutants of cya1, but not cya2, were immotile. Disruption of the cya1
      gene also caused reduction of cellular cAMP level. The cya1 mutant cells regained
      motility when cAMP was added exogenously.

PMID- 10202819
TI  - Impact of drug resistance mutations on virologic response to salvage therapy.
      Swiss HIV Cohort Study.
AB  - OBJECTIVE: To assess the prognostic significance of drug-associated mutations in
      the protease and reverse transcriptase (RT) genes on virological response to
      salvage therapy. PATIENTS: All patients from four centres of the Swiss HIV Cohort
      Study who were switched, between February and October 1997, to nelfinavir plus
      other antiretroviral drugs following failure of highly active antiretroviral
      therapy (HIV-1 RNA >1000 copies/ml after > 3 months). METHODS: Direct sequencing
      of RT and protease genes derived from plasma RNA was performed in 62 patients
      before salvage therapy. Baseline predictors (drug-resistance mutations, drug
      exposure, clinical and biological parameters) of virological response after 4-12
      weeks of therapy were assessed by linear regression analyses. RESULTS: Patients
      had been treated with RT inhibitors and protease inhibitors for a median duration
      of 35.6 and 12.2 months, respectively. Baseline median CD4 cell count was 113 x
      10(6)/l and HIV-1 RNA 5.16 log10 copies/ml. The median decrease of HIV-1 RNA was
      0.38 log10; 32% of the patients showed > 1 log10 decrease. At baseline, 90% of
      the patients had RT inhibitor-resistance mutations with a median number per
      patient of four (range, 0-7). Primary and secondary protease inhibitor-resistance
      mutations were detected in 69% and 89% of the patients, respectively. The median
      number of total protease inhibitor-resistance mutations per patient was four
      (range, 0-9). In univariate analysis, virological response to salvage therapy was
      associated with number of RT inhibitors, primary and secondary protease inhibitor
      resistance mutations, history of protease inhibitor use (duration and number),
      but not with clinical stage, HIV-1 RNA level or CD4 cell count. After adjustment
      for all variables, the number of RT inhibitor plus protease inhibitor-resistance
      mutations was the only independent predictor. CONCLUSIONS: In patients with
      advanced HIV infection, the virological response to salvage therapy containing
      nelfinavir is best predicted by the number of baseline RT inhibitor plus protease
      inhibitor-resistance mutations.

PMID- 10202821
TI  - Sexual transmission of HIV: infectiousness and prevention.

PMID- 10202820
TI  - Virologic responses to a ritonavir--saquinavir-containing regimen in patients who
      had previously failed nelfinavir.
AB  - OBJECTIVES: The effectiveness of a second protease inhibitor in patients who
      failed an initial protease inhibitor is unclear but believed to be low. It has
      been postulated, however, that patients who fail nelfinavir may respond
      differently. We therefore assessed the virologic response to a ritonavir
      saquinavir-containing regimen in patients who had previously failed nelfinavir.
      METHODS: A total of 26 patients enrolled in the nelfinavir clinical trials AG506
      and AG511 at our two sites who failed (two consecutive HIV viral loads > 5000
      copies/ml; branched DNA assay) were switched to a combination of stavudine 40 mg
      twice daily, lamivudine 150 mg twice daily, ritonavir 400 mg twice daily and
      saquinavir 400 mg twice daily. RESULTS: The mean viral load at enrollment in this
      study was 46 674 copies/ml (range, 1075-146400 copies/ml). The median CD4 cell
      count was 222 x 10(6)/l (range, 82-448 x 10(6)/l). The median duration of
      nelfinavir use with a detectable viral load before the switch occurred was 48
      weeks. Two patients discontinued the study at 3 weeks. All of the remaining
      patients (n = 24) reached undetectable viral loads (< 500 copies/ml) that were
      sustained at week 24 in 17 (71%) out of 24 subjects. The most frequent baseline
      mutations in the protease gene prior to switching were D30N (13 out of 18), N88D
      (eight out of 18) and M36I (eight out of 18). The presence or absence of these
      mutations was not predictive of a short-term virologic response. CONCLUSIONS:
      Most patients who failed a nelfinavir-containing regimen responded to a switch to
      a combination regimen with saquinavir-ritonavir.

PMID- 10202822
TI  - Differential expression profiles of apoptosis-affecting genes in HIV-infected
      cell lines and patient T cells.
AB  - OBJECTIVE: To clarify the molecular mechanisms of HIV-induced apoptosis. DESIGN:
      The assessment of expression patterns for genes affecting the interrelated cell
      cycle and apoptosis processes in HIV-1LAI-infected T lymph oblastoid (CEM) cells,
      as well as CD4 and CD8 cells from HIV-infected individuals and controls. METHODS:
      The kinetics of HIV infection in CEM cells were defined by flow cytometry of
      green fluorescent protein expression from a reporter vector. Apoptosis of CEM
      cells was measured by propidium iodine staining and flow cytometry. Gene
      expression levels were determined by a multiprobe RNase protection assay.
      RESULTS: The infection and apoptosis of CEM cells were associated with enhanced
      expression of Bax, Bcl-2, Bcl-X(L) and caspase 1 (ICE). There was increased
      expression of Bcl-2 and caspase 1 and decreased expression of cyclin-dependent
      kinase inhibitor p21CIP1 in CD4 cells of HIV-infected individuals compared with
      uninfected controls. The CD8 cells of HIV-infected individuals exhibited
      increased expression of Bcl-2, Bcl-X(L), Bax and caspase 1 but, in contrast to
      the CD4 subset, they showed elevated expression of p21CIP1 and p16INK4a compared
      with controls. CONCLUSIONS: The Bax increase in CEM cells appears to be a direct
      effect associated with a high frequency of infection and apoptosis, because it
      was not found in the CD4 cells of patients. In contrast, the increase of Bax in
      the CD8 cells of patients seems to be an indirect effect. Increases in Bcl-2, Bcl
      X(L) and caspase 1 in HIV-infected CEM cells may be caused by both direct and
      indirect mechanisms, because they also occurred in CD4 and CD8 cells of HIV
      infected individuals. In addition, the low expression of p21CIP1 in the CD4
      subset of HIV-infected individuals could promote apoptosis, whereas the high
      expression of p21CIP1 and p16INK4a in the CD8 subset may lead to a state of
      anergy, akin to replicative senescence.

PMID- 10202823
TI  - Immunopathology as a result of highly active antiretroviral therapy in HIV-1
      infected patients.
AB  - OBJECTIVE: Unusual clinical inflammatory syndromes associated with underlying
      previously unrecognized opportunistic infections are increasingly being noted
      shortly after starting highly active antiretroviral therapy (HAART). This study
      examined the possible relationship between such unexpected disease manifestations
      and in vitro parameters of microbial antigen-specific immune reactivity in
      patients infected with HIV-1 who had a Mycobacterium avium intracellulare or
      Mycobacterium xenopi infection. DESIGN: In vitro T-cell proliferation experiments
      were performed after specific stimulation of a patient's peripheral blood
      mononuclear cells (PBMC) with M. avium and M. xenopi antigen and non-specific
      stimulation with phytohaemagglutinin (PHA). The results were compared with
      appropriate controls. PATIENTS: Five patients who presented with unusual clinical
      syndromes associated with M. avium or M. xenopi infection within weeks of
      experiencing large rises in CD4+ cell counts following the initiation of
      antiretroviral therapy. RESULTS: In all patients except one, mycobacteria
      specific lymphoproliferative responses rose significantly following HAART; this
      was temporally associated with elevations in CD4+ cell counts and the occurrence
      of clinical disease. The patient with M. xenopi infection appeared to clear his
      infection subsequently without antimycobacterial therapy. In three of the four
      patients with M. avium infection, antimycobacterial treatment could be stopped
      without recurrence of infection. CONCLUSION: Our findings support the hypothesis
      that HAART may lead to clinically relevant inflammation as a result of
      restoration of specific immune reactivity against microbial pathogens that are
      subclinically present at the time treatment is initiated. Continuation of HAART
      may subsequently result in protective immunity and clearance of infection.

PMID- 10202824
TI  - Persistent alterations in T-cell repertoire, cytokine and chemokine receptor gene
      expression after 1 year of highly active antiretroviral therapy.
AB  - OBJECTIVES: To examine T-cell repertoire modifications, the evolution of T-helper
      (TH)1/TH2 cytokine imbalance and modifications in chemokine receptor expression
      when the viral load is decreased by 2-3 log10 copies/ml under highly active
      antiretroviral therapy (HAART). DESIGN: Sixteen patients previously treated with
      zidovudine and lamivudine, with CD4 cells below 300 x 10(6)/l and viraemia above
      30000 copies/ml were treated by saquinavir and ritonavir together with both
      reverse transcriptase (RT) inhibitors (ANRS 069 trial). T-cell repertoire,
      chemokine receptor and lymphokine expression were studied from peripheral blood
      mononuclear cells sampled at weeks 0, 24 and 48. METHODS: T-cell repertoire study
      was carried out using the Immunoscope method. Interleukin (IL)-12 receptor beta2,
      CC-chemokine receptor (CCR)-3, CXC-chemokine receptor-4 and CCR-5 expression in
      CD4+ cells was measured by kinetic quantitative PCR and IL-2, IL-4, IL-10, IL-13,
      interferon (IFN)-gamma were measured using a quantitative RT-PCR assay with
      homologous internal standards. RESULTS: Repertoire alterations were more frequent
      in CD4- than in CD4+ cells and persisted despite undetectable viraemia. Increased
      CCR-3 expression and spontaneous IFN-gamma as well as mitogenic induced IL-13
      were observed at baseline and decreased slightly under HAART. CONCLUSION: The
      CD8+ cell repertoire alterations were profound, whereas the CD4+ cell alterations
      were moderate and both persisted unchanged under HAART. The TH1/TH2 imbalance was
      more related to TH2 over-expression than to TH1 deficiency and persisted for at
      least 1 year under HAART.

PMID- 10202825
TI  - CD4+ and CD8+ lymphocytes and HIV RNA in HIV infection: high baseline counts and
      in particular rapid decrease of CD8+ lymphocytes predict AIDS.
AB  - OBJECTIVE: To study the progression of HIV infection in relation to immunological
      and virological variables with emphasis on the role of CD8+ lymphocytes. DESIGN:
      Prospective follow-up from October 1991 of patients observed for at least 18
      months allowing nucleoside analogue monotherapy. Peripheral CD4+ and CD8+
      lymphocyte counts, HIV RNA, and soluble CD8 were analysed by statistics allowing
      the evaluation of serial data, avoiding time points with concurrent infections.
      SETTING: Tertiary university clinic. PATIENTS: Forty-nine patients were followed
      for 52.6 months, baseline CD4+ count of 300 x 10(6)/l, sample interval of 5.9
      months (medians). MAIN OUTCOME MEASURES: AIDS, death, and CDC groups B- or C
      related events. RESULTS: AIDS developed in 28% of patients. Baseline CD8+ counts
      above the median were significantly associated with AIDS development; the best
      Cox model included CD8+ cells and the log10RNA/CD4 ratio. A decline in CD8+
      counts relative to baseline most significantly predicted AIDS, along with higher
      baseline RNA and actual CD4+ counts of less than 200 x 10(6)/l. Levels of soluble
      CD8 in the blood relative to total CD8+ cells significantly increased in patients
      developing AIDS. Death occurred in 16% of the patients, and was only predicted by
      high CD8+ cell counts at baseline. CDC B- and C-related events occurred in 35% of
      the patients and were best predicted by high baseline CD8+ counts and high RNA
      levels. CONCLUSIONS: The serial quantitation of CD8+ lymphocytes gave highly
      significant predictive information on the natural progression of HIV infection in
      patients with moderate to severe immune deficiency. Our data suggest that the
      hyperactivation of CD8+ lymphocytes is an important factor leading to a numerical
      decrease of CD8+ lymphocytes in progressive HIV infection.

PMID- 10202826
TI  - Immune restoration does not invariably occur following long-term HIV-1
      suppression during antiretroviral therapy. INCAS Study Group.
AB  - BACKGROUND: Current antiretroviral treatment can induce significant and sustained
      virological and immunological responses in HIV-1-infected persons over at least
      the short- to mid-term. OBJECTIVES: In this study, long-term immune
      reconstitution was investigated during highly active antiretroviral therapy.
      METHODS: Patients enrolled in the INCAS study in The Netherlands were treated for
      102 weeks (range 52-144 weeks) with nevirapine (NVP) + zidovudine (ZDV) (n = 9),
      didanosine (ddl) + ZDV (n = 10), or NVP + ddl + ZDV (n = 10). Memory and naive
      CD4+ and CD8+ T cells were measured using CD45RA and CD27 monoclonal antibodies
      (mAb), T-cell function was assayed by CD3 + CD28 mAb stimulation, and plasma HIV
      1 RNA load was measured by ultra-direct assay (cut-off < 20 copies/ml). RESULTS:
      Compared to both double combination regimens the triple combination regimen
      resulted in the most sustained increase in CD4+ T cells (change in CD4+, + 253 x
      10(6) cells/l; standard error, 79 x 10(6) cells/l) and reduction of plasma HIV-1
      RNA. In nine patients (31%) (ddl + ZDV, n = 2; NVP + ddl + ZDV, n = 7) plasma HIV
      1 RNA levels remained below cut-off for at least 2 years. On average, these long
      term virological responders demonstrated a significantly higher increase of naive
      and memory CD4+ T cells (P = 0.01 and 0.02, respectively) as compared with
      patients with a virological failure, and showed improved T-cell function and
      normalization of the naive; memory CD8+ T-cell ratio. However, individual
      virological success or failure did not predict the degree of immunological
      response. T-cell patterns were independent of baseline CD4+ T-cell count, T-cell
      function, HIV-1 RNA load or age. Low numbers of naive CD4+ T cells at baseline
      resulted in modest long-term naive T-cell recovery. CONCLUSIONS: Patients with
      prolonged undetectable plasma HIV-1 RNA levels during antiretroviral therapy do
      not invariably show immune restoration. Naive T-cell recovery in the setting of
      complete viral suppression is a gradual process, similar to that reported for
      immune recovery in adults after chemotherapy and bone marrow transplantation.

PMID- 10202827
TI  - Ritonavir and saquinavir combination therapy for the treatment of HIV infection.
AB  - OBJECTIVE: To evaluate the safety and antiretroviral activity of ritonavir
      (Norvir) and saquinavir (Invirase) combination therapy in patients with HIV
      infection. DESIGN: A multicenter, randomized, open-label clinical trial. SETTING:
      Seven HIV research units in the USA and Canada. PATIENTS: A group of 141 adults
      with HIV infection, CD4 T lymphocyte counts of 100-500 x 10(6) cells/l, whether
      treated previously or not with reverse transcriptase inhibitor therapy, but
      without previous HIV protease inhibitor drug therapy. INTERVENTIONS: After
      discontinuation of prior therapy for 2 weeks, group I patients were randomized to
      receive either combination (A) ritonavir 400 mg and saquinavir 400 mg twice daily
      or (B) ritonavir 600 mg and saquinavir 400 mg twice daily. After an initial
      safety assessment of group I patients, group II patients were randomized to
      receive either (C) ritonavir 400 mg and saquinavir 400 mg three times daily or
      (D) ritonavir 600 mg and saquinavir 600 mg twice daily. Investigators were
      allowed to add up to two reverse transcriptase inhibitors (including at least one
      with which the patient had not been previously treated) to a patient's regimen
      after week 12 for failure to achieve or maintain an HIV RNA level < or = 200
      copies/ml documented on two consecutive occasions. MEASUREMENTS: Plasma HIV RNA
      levels and CD4+ T-lymphocyte counts were measured at baseline, every 2 weeks for
      2 months, and monthly thereafter. Safety was assessed through the reporting of
      adverse events, physical examinations, and the monitoring of routine laboratory
      tests. RESULTS: The 48 weeks of study treatment was completed by 75% (106/141) of
      the patients. Over 80% of the patients on treatment at week 48 had an HIV RNA
      level < or = 200 copies/ml. In addition, intent-to-treat and on-treatment
      analyses revealed comparable results. Suppression of plasma HIV RNA levels was
      similar for all treatment arms (mean areas under the curve minus baseline through
      48 weeks were-1.9, -2.0, -1.6, -1.8 log10 copies/ml in ritonavir-saquinavir 400
      400 mg twice daily, 600-400 mg twice daily, 400-400 mg three times daily, and 600
      600 mg twice daily, respectively). Median CD4 T-lymphocyte count rose by 128 x
      10(6) cells/l from baseline, with an interquartile range (IQR) of 82-221 x 10(6)
      cells/l. The most common adverse events were diarrhea, circumoral paresthesia,
      asthenia, and nausea. Reversible elevation of serum transaminases (> 5 x upper
      limit of normal) occurred in 10% (14/141) of the patients enrolled in this study
      and was associated with baseline abnormalities in liver function tests, baseline
      hepatitis B surface antigen positivity, or hepatitis C antibody positivity
      (relative risk, 5.0; 95% confidence interval 1.5-16.9). Most moderate or severe
      elevations in liver function tests occurred in patients treated with ritonavir
      saquinavir 600-600 mg twice daily. CONCLUSIONS: Ritonavir 400 mg combined with
      saquinavir 400 mg twice daily with the selective addition of reverse
      transcriptase inhibitors was the best-tolerated regimen of four dose-ranging
      regimens and was equally as active as the higher dose combinations in HIV
      positive patients without previous protease inhibitor treatment.

PMID- 10202828
TI  - Stavudine in zidovudine (ZDV)-experienced compared with ZDV-naive patients.
AB  - OBJECTIVE: To assess the effect of prior zidovudine (ZDV) use on subsequent
      response to stavudine (D4T)-containing regimens. DESIGN: Analysis of data from
      prospective observational database. METHODS: Patients were ZDV-experienced if
      they had previously received more than 90 days of ZDV and ZDV-naive if they had
      never received ZDV. HIV-1 RNA and CD4 cell counts were compared at 3, 6, and 12
      months after initiation of D4T. Univariate and multivariate analyses were
      performed, adjusting for baseline HIV-1 RNA and CD4 cell count, age, sex, race,
      HIV transmission category, time since enrollment, and protease inhibitor use.
      RESULTS: No difference was found between ZDV-experienced (n = 130) and naive (n =
      98) patients in age, sex, race, transmission category, use of a concurrent
      protease inhibitor, or baseline CD4 cell count and HIV-1 RNA. There was no
      difference in the median decline in HIV-1 RNA (-1.29 log10 copies/ml for
      experienced patients versus -1.19 log10 copies/ml for naive patients; P = 0.39),
      in achieving HIV-1 RNA < 400 copies/ml at 3 months (51% versus 49%; P = 0.79) or
      6 months (48% versus 56%; P = 0.33). There was no difference in CD4 cell response
      (+73 x 10(6)/l versus + 87 x 10(6)/l; P = 0.51). By multivariate adjustment in a
      repeated measures analysis, there was no significant difference in achieving
      undetectable HIV-1 RNA or in CD4 cell response between experienced and naive
      patients. CONCLUSION: No difference in response to a D4T-containing regimen
      between ZDV-experienced and naive patients was found over a 1-year period. In
      contrast to previous trials, most patients in this study also received a protease
      inhibitor. These findings may be more relevant in the current era of highly
      active antiretroviral therapy.

PMID- 10202830
TI  - Monitoring changes in fat-free mass in HIV-positive men with hypotestosteronemia
      and AIDS wasting syndrome treated with gonadal hormone replacement therapy.
AB  - OBJECTIVE: To compare methods for assessing changes in body composition during
      gonadal hormone replacement therapy in a group of HIV-positive men with AIDS
      wasting syndrome. DESIGN: The study included a 21-day, double-blind, randomized,
      placebo-controlled inpatient intervention and a 12-week open-label intervention.
      The inpatient intervention included 18 men who were confined to a metabolic ward.
      Days 1-7 comprised weight stabilization and body composition measures followed by
      14 days of nandrolone decanoate at either 65 or 195 mg weekly, or placebo, and
      repeat testing. The open-label intervention comprised 12 weeks of 200 mg
      nandrolone decanoate fortnightly with measurements of fat-free mass at 6 and 12
      weeks. METHODS: The inpatient intervention measured nitrogen balance from 24 h
      urine and fecal collections and fat-free mass by dual energy x-ray absorptiometry
      (DEXA), bioimpedance spectroscopy (BIS) and D2O dilution. Nitrogen balance was
      calculated as the difference between dietary intake and urinary and fecal
      nitrogen excretion. Nitrogen was converted to fat-free mass using the constant of
      32.5 g. Repeated measures analysis of variance was used to determine which
      methods were significantly different from the reference nitrogen balance
      technique. RESULTS: Nitrogen accretion of lean tissue was 0.55 and 0.85 kg weekly
      for low and high-dose groups, respectively. Estimated nitrogen retention during
      the open-label study was 0.42 kg weekly. Body weight increased with the estimated
      lean tissue accretion. DEXA, BIS and D2O methods demonstrated improvements in fat
      free mass, although the BIS estimate of fat-free mass most closely matched the
      results of the nitrogen retention method. CONCLUSION: DEXA, BIS and D2O
      techniques demonstrated increases in fat-free mass. The BIS method is less
      costly, more convenient to use, and had results that more closely matched those
      from nitrogen balance and retention methods. BIS may be the preferred method to
      monitor changes in fat-free mass in AIDS patients and patients with malnutrition.

PMID- 10202829
TI  - Short-term progressive resistance training increases strength and lean body mass
      in adults infected with human immunodeficiency virus.
AB  - BACKGROUND: To assess the efficacy of progressive resistance training (PRT) in
      increasing strength and lean body mass (LBM) in HIV-infected adults. METHODS:
      Twenty-five adults with HIV infection were trained using a highly intensive PRT
      regimen for 8 weeks, followed by an additional 8 weeks of observation under ad
      libitum physical activity conditions. RESULTS: Twenty-four of the 25 patients
      completed the first phase of the study. They had significant increases in
      strength on all four exercises tested (P < 0.0001), and an increase in LBM of
      1.75 +/- 1.94 kg (mean +/- SD, P < 0.0002), with a concomitant decline in fat of
      0.92 +/- 2.22 kg (P < 0.05), and no significant change in weight or bone mineral
      content. Twenty-one of the patients returned for follow-up 8 weeks after
      completing the PRT. Compared with their baseline values, their mean lean mass
      remained 1.40 +/- 1.8 kg higher (P < 0.003). Among those who continued to train
      to some extent, lean mass increased by a mean of 1.1 +/- 1.6 kg (n = 9, P < 0.05
      versus end of PRT), whereas those who did no further training showed an increase
      in lean mass of 0.28 +/- 1.4 kg (n = 12, P = NS versus end of PRT). The
      difference between the two groups was not, however, significant (P = 0.25). Among
      six patients with AIDS wasting, the increase in LBM was larger than among non
      wasted patients (2.8 versus 1.4 kg, P < 0.06), and there was an increase in both
      weight (+3.9 versus -0.2 kg, P < 0.002) and fat mass (+ 0.95 versus -1.5 kg, P <
      0.002) at 8 weeks, which persisted at 16 weeks (weight: +4.0 versus -1.6 kg, P <
      0.0002; fat: +1.6 versus -1.9 kg, P < 0.01). CONCLUSION: This preliminary study
      suggests that short-term, high intensity PRT can significantly increase LBM and
      strength in HIV infection, and may be used as an alternative or adjunct to
      pharmacological anabolic treatments in this disease.

PMID- 10202831
TI  - Increasing survival time after AIDS in Italy: the role of new combination
      antiretroviral therapies. Tuscany AIDS Study Group.
AB  - BACKGROUND: In Italy, antiretroviral combination therapy was adopted in mid-1995
      and protease inhibitors in mid-1996. OBJECTIVE: To conduct a prospective,
      population-based, observational study to evaluate the effect of these therapies
      on the survival of persons with AIDS (PWA). METHODS: PWA living in the Tuscany
      region diagnosed between 1985 and 31 March 1997 (National AIDS Registry) were
      studied. Information on antiretroviral drugs, prophylactic treatment, CD4 cell
      count, and AIDS-defining illnesses was collected for PWA still alive at 1 January
      1996 and those diagnosed thereafter (analysis cut-off date, 30 November 1997).
      Kaplan-Meier curves were calculated by year of diagnosis. A Cox model was then
      used to estimate the adjusted (by sex, age, HIV exposure category, CD4 cell
      count, type and number of AIDS-defining illnesses) relative hazard (RH) of death
      by year of diagnosis and calendar date (considered as a time-dependent variable).
      Similar analyses were repeated for PWA diagnosed after 1989, having been
      stratified by disease-specific AIDS condition. A final analysis was performed for
      PWA still alive at 1 January 1996 or diagnosed thereafter for estimating the
      effect of single, double and triple combination therapy (time-dependent
      variables), having adjusted for the above variables and for prophylactic
      treatment. RESULTS: A total of 1683 (79.5%) out of 2118 PWA died before 1
      December 1997. Use of more potent combination therapies, including protease
      inhibitors, greatly increased during 1997. Median survival was 2.9, 12.3, 13.4,
      11.4 and 17.6 months for diagnoses before 1987, in 1987-1990, 1991-1993, 1994 and
      1995, respectively; an estimated 62% of those diagnosed in 1996-1997 had survived
      15 months after diagnosis. The Cox model showed a trend of decrease of RH for
      calendar time starting in the first half of 1996, compared with 1994. When
      stratifying by specific AIDS-defining disease there was no statistically
      significant evidence that the improved overall survival was due to increased
      survival only for certain diseases. The final multivariate analysis for the 771
      PWA still alive at 1 January 1996 or diagnosed thereafter estimated significant
      RH < 1.0 for double and triple therapy (RH, 0.61 and 0.36, respectively) compared
      with no therapy. CONCLUSIONS: A significant reduction in risk of death after AIDS
      was observed from the second half of 1996, apparently due to the widespread use
      of antiretroviral combination therapies.

PMID- 10202832
TI  - A prospective study of HIV disease progression in female and male drug users.
AB  - OBJECTIVE: To compare HIV disease progression and mortality in a cohort of female
      and male drug users. DESIGN: A prospective cohort study of 222 HIV-seropositive
      women and 302 HIV-seropositive men who attended a hospital-affiliated methadone
      maintenance program with on-site primary care. METHODS: Regression slopes of CD4+
      cell decline were compared using the two sample t-test, and the distribution of
      AIDS-defining illnesses evaluated by Mantel-Haenszel chi2 test. Time to AIDS
      defining clinical conditions and death were compared using the Kaplan-Meier log
      rank test. Multivariate estimates of progression to clinical AIDS or death, for
      all participants, stratified by sex, were derived from Cox proportional hazards
      models. RESULTS: Ninety-five persons (43 women and 52 men) developed AIDS
      defining conditions. Analyses of the rates of CD4+ cell decline, the distribution
      of first AIDS-defining illnesses, and the time to clinical AIDS did not differ by
      sex. In the multivariate model, sex was not associated with an AIDS outcome,
      whereas crack-cocaine use [hazards ratio (HR), 1.815; 95% confidence interval
      (CI), 1.151-2.863], CD4+ cell count (100 x 10(6)/l; HR, 0.589; 95% CI, 0.511
      0.679), and two or more HIV-related symptoms (HR, 1.702; 95% CI, 1.125-2.576)
      were associated. Mortality rates (8.71 per 100 person-years in women and 9.85 per
      100 person-years in men) were similar, using univariate or multivariate methods.
      CONCLUSIONS: There was little difference in clinical outcomes or mortality
      between HIV-seropositive female and male drug users with access to primary care.
      However, crack-cocaine use was independently associated with progression to
      clinical AIDS.

PMID- 10202833
TI  - AIDS diagnoses at higher CD4 counts in Australia following the introduction of
      highly active antiretroviral treatment.
AB  - OBJECTIVES: To assess whether AIDS cases in Australia have been diagnosed at
      higher CD4 counts since the widespread availability of highly active
      antiretroviral treatment (HAART) in mid-1996. METHODS: Data on the CD4 count at
      AIDS diagnosis for AIDS cases diagnosed between 1 January 1992 and 31 December
      1997, and reported to the National AIDS Registry in Australia by 31 March 1998,
      were analysed. The median CD4 count at AIDS diagnosis, and the proportions of
      AIDS diagnoses with a CD4 count above 100 cells/microl, and above 200
      cells/microl, were calculated by the year of diagnosis, both for all AIDS
      defining illnesses, and for each illness separately. Analyses were also
      stratified by the time interval between HIV and AIDS diagnoses (less than or
      equal to, or more than, 3 months) because people diagnosed with HIV close to the
      diagnosis of AIDS would generally not have received any antiretroviral treatment
      before the diagnosis of AIDS, and so no trends in CD4 counts at the diagnosis of
      AIDS would be expected in this group. RESULTS: There was an increase in CD4 count
      at AIDS diagnosis in 1996 and 1997, although this increase was only apparent for
      AIDS-defining illnesses other than Pneumocystis carinii pneumonia (PCP), and was
      limited to AIDS cases diagnosed with HIV more than 3 months before AIDS. In cases
      of AIDS other than PCP, and diagnosed with HIV more than 3 months before AIDS,
      the median CD4 count increased from 50 cells/microl in 1995 to 80 cells/microl in
      1996 and 134 cells/microl in 1997. CONCLUSIONS: There has been an increase in the
      CD4 count at AIDS diagnosis for most AIDS-defining illnesses in Australia
      coincident with the widespread availability of HAART.

PMID- 10202834
TI  - Selective versus universal antenatal HIV testing: epidemiological and
      implementational factors in policy choice.
AB  - OBJECTIVE: To develop an epidemiological basis for economic analyses of selective
      and universal antenatal screening strategies, and to apply it to the UK. METHODS:
      The prevalence of higher-risk women and the prevalence of undiagnosed infection
      within groups of high-risk and low-risk women was estimated from surveillance and
      survey data. The numbers of women tested and the numbers of infected women who
      would be identified by universal and selective strategies were then calculated
      under a range of assumptions about the identification of higher-risk women and
      acceptance of testing. RESULTS: In higher-risk women estimated prevalence of
      undiagnosed infection was between 0.06% and 2.8%, comparing well with independent
      estimates. In low-risk women, estimates ranged from 0.014% in London to 0.002% in
      the rest of the UK. If uptake among the high-risk women was the same in selective
      and universal strategies, universal testing would entail testing between 7100
      (London) and 50000 (rest of England) additional women to detect an additional
      case. However, if selective screening identified only 60% of those at high risk
      and achieved only 60% acceptance compared with a universal programme, then
      universal screening would require only 1150 additional women to identify one
      additional case in London, compared to 6470 in Scotland and 13140 in the rest of
      the UK. CONCLUSIONS: Overall prevalence does not form an adequate basis for
      determining screening strategy. Instead, universal screening can be justified
      either because the prevalence of HIV in the low-risk group is sufficiently high,
      or because it achieves sufficiently higher uptake relative to selective screening
      among those at higher risk.

PMID- 10202835
TI  - The impact of body composition analysis in HIV-infected patients: quantifying
      therapeutic effects.

PMID- 10202836
TI  - Formation and release of virus-like particles by HIV-1 matrix protein.

PMID- 10202837
TI  - Potential interaction of antiretroviral therapy with paclitaxel in patients with
      AIDS-related Kaposi's sarcoma.

PMID- 10202838
TI  - Drug interaction of isotretinoin and protease inhibitors: support for the
      cellular retinoic acid-binding protein-1 theory of lipodystrophy?

PMID- 10202839
TI  - Combined stavudine and lamivudine during pregnancy.

PMID- 10202840
TI  - Impact of Kaposi's sarcoma on HIV disease progression.

PMID- 10202841
TI  - HIV-1 subtypes and plasma RNA quantification.

PMID- 10202842
TI  - RANTES upregulation by HIV-1-infected cells: lack of correlation with viral
      replication and induction of interferon.

PMID- 10202843
TI  - Small differences in CD4+ T-cell production may go unnoticed.

PMID- 10202844
TI  - Impact of highly active antiretroviral therapy on clinical evolution of genital
      warts in HIV-infected patients.

PMID- 10202845
TI  - Prevalence and underestimation of pain in HIV-infected patients by physicians: a
      cross-sectional study in a day care hospital.

PMID- 10202846
TI  - Place of antiretroviral drugs in the treatment of HIV-infected people in Africa.
      International AIDS Society.

PMID- 10202847
TI  - Nitration modifying function of proteins, hormones and neurotransmitters.
AB  - Several lines of evidence have been accumulated for occurrence of nitration in
      vivo. In this brief review, we summarized nitration studies on functional changes
      of proteins, hormones and neurotransmitters, before as well as after the
      discovery of peroxynitrite. Most of nitrated molecules exhibit less active
      properties than the parental compounds. It is still unknown whether nitration is
      merely a footprint of oxidative stress, an important pathway of nitric oxide
      metabolisms or a part of integral processes for maintaining cellular homeostasis.

PMID- 10202848
TI  - Inhibition of the angiotensin II Type 1 receptor by TCV-116: quantitation by in
      vitro autoradiography.
AB  - Inhibition of angiotensin (Ang) II type 1 (AT1) receptors in various target
      tissues of adult Sprague-Dawley rats was studied after single oral administration
      of TCV-116. The effects of TCV-116 on Ang II-receptor binding were assessed by
      quantitative in vitro autoradiography using 125I-[Sar1,Ile8]Ang II as a ligand.
      Four hours after the administration of TCV-116 (1 mg/kg), Ang II-receptor binding
      was markedly inhibited in the kidney (20% of control), adrenal cortex (27%),
      thoracic aorta (57%), heart (55%) and testis (76%) where AT1 receptors
      predominate. In the brain, orally administered TCV-116 produced a significant
      inhibition of binding both to the circumventricular organs (38%), which are
      devoid of the blood-brain barrier (BBB), and to the discrete regions within the
      BBB such as the paraventricular hypothalamic nucleus (48%), nucleus of the
      solitary tract (60%). Twenty-four hours after the administration, Ang II-receptor
      binding had partly recovered to approximately 50-85% of control levels. In
      contrast, throughout the experimental period, Ang II-receptor binding was little
      affected in sites where Ang II type 2 (AT2) receptors predominate such as the
      adrenal medulla and the nucleus of the inferior olive. These data indicate that
      orally administered TCV-116 specifically binds to AT1 receptors both in
      peripheral tissues and the central nervous system.

PMID- 10202849
TI  - Supraspinal neurotensin-induced antianalgesia in mice is mediated by spinal
      cholecystokinin.
AB  - Intracerebral injection of neurotensin into specific brain loci in rats produces
      hyperalgesia due to the release of cholecystokinin (CCK) in the spinal cord. The
      present purpose was to show in another species that neurotensin can antagonize
      the antinociceptive action of morphine through the spinal CCK mechanism in mice.
      Neurotensin given intracerebroventricularly (i.c.v.) at doses higher than 100 ng
      produced antinociception in the tail flick test. However, at lower doses between
      1 pg to 25 ng, neurotensin antagonized the antinociceptive action of morphine
      given intrathecally (i.t.), thus demonstrating the antianalgesic activity of
      neurotensin. The rightward shift in the morphine dose-response curve produced by
      i.c.v. neurotensin was eliminated by an i.t. pretreatment with CCK8 antibody (5
      microl of antiserum solution diluted 1:1000). I.t. administration of lorglumide,
      a CCK(A)-receptor antagonist (10-1000 ng), and PD135,158, a CCK(B)-receptor
      antagonist (250-500 ng), also eliminated the antianalgesic action of neurotensin.
      Thus, the mechanism of the antianalgesic action of neurotensin given i.c.v.
      involved spinal CCK. This mode of action is similar to that for the antianalgesic
      action of supraspinal pentobarbital which also involves spinal CCK.

PMID- 10202850
TI  - Effects of NTE-122, a novel acyl-CoA:cholesterol acyltransferase inhibitor, on
      cholesterol esterification and secretions of apolipoprotein B-containing
      lipoprotein and bile acids in HepG2.
AB  - We studied the effect of NTE-122 (trans-1,4-bis[[1-cyclohexyl-3-(4-dimethylamino
      phenyl) ureido]methyl]cyclohexane), a novel acyl-CoA:cholesterol acyltransferase
      (ACAT) inhibitor, on intracellular cholesterol esterification and the secretion
      of apolipoprotein B100 (apoB)-containing lipoprotein and bile acids in the human
      hepatoma cell line HepG2. NTE-122 markably inhibited [3H]oleate incorporation
      into cholesteryl esters in HepG2 cells incubated with 5 microg/ml 25
      hydroxycholesterol as a stimulus for ACAT (IC50=6.0 nM). On the other hand, NTE
      122 did not affect [3H]oleate incorporation into triglycerides and phospholipids
      and [14C]acetate incorporation into cholesterol. The stimulation of ACAT by 25
      hydroxycholesterol caused significant increases in the secretion of radiolabeled
      cholesteryl esters, radiolabeled triglycerides and apoB mass. NTE-122
      pronouncedly inhibited the secretion of radiolabeled cholesteryl esters in
      proportion to the inhibition of cellular cholesterol esterification, and it
      significantly reduced the secretion of radiolabeled triglycerides and apoB mass
      in HepG2 cells incubated with 25-hydroxycholesterol. Furthermore, NTE-122
      increased the secretion of bile acids synthesized from [14C]-cholesterol. These
      results suggest that NTE-122 is capable of exhibiting anti-hyperlipidemic effects
      by reducing both the cholesterol content and the amount of secreted very low
      density lipoprotein and enhancing the excretion of bile acid from the liver.

PMID- 10202851
TI  - Effects of NTE-122, a novel acyl-CoA:cholesterol acyltransferase inhibitor, on
      cholesterol esterification and high-density lipoprotein-induced cholesterol
      efflux in macrophages.
AB  - We investigated the effects of a novel acyl-CoA:cholesterol acyltransferase
      (ACAT) inhibitor, NTE-122 (trans-1,4-bis[[1-cyclohexyl-3-(4-dimethylamino
      phenyl)ureido]methyl]cyclohexane), on ACAT activities in macrophages originating
      from several species and high-density lipoprotein (HDL)-induced cholesterol
      efflux in phorbol 12-myristate 13-acetate (PMA)-treated THP-1 cells. NTE-122
      inhibited cell-free ACAT activities in human PMA-treated THP-1 cells and mouse
      J774.1 cells with IC50 values of 0.88 and 360 nM, respectively. NTE-122
      competively inhibited the ACAT activity in PMA-treated THP-1 cells. NTE-122 also
      inhibited cellular ACAT activities in PMA-treated THP-1 cells, rat peritoneal
      macrophages and J774.1 cells with IC50 values of 3.5, 84 and 6800 nM,
      respectively. Furthermore, NTE-122 prevented cholesterol accumulation in PMA
      treated THP-1 cells incubated with acetylated low density lipoprotein,
      simultaneously with HDL, while it caused accumulation of a significant amount of
      free cholesterol in the absence and even in the presence of HDL. NTE-122 also
      enhanced HDL-induced cholesterol efflux from established foam cells converted
      from PMA-treated THP-1 cells. These results suggest that NTE-122, capable of
      inhibiting macrophage ACAT activity in humans more strongly than those in the
      other species, exhibits anti-atherogenic effects by preventing the foam cell
      formation and enhancing the foam cell regression in humans.

PMID- 10202852
TI  - Antinociceptive effect of Gosha-jinki-gan, a Kampo medicine, in streptozotocin
      induced diabetic mice.
AB  - We evaluated the antinociceptive effect of Gosha-jinki-gan, a Kampo medicine
      including processed Aconiti tuber, and its mechanism in streptozotocin-induced
      diabetic mice. Gosha-jinki-gan (0.1-1.0 g/kg, p.o.) showed a more potent
      antinociceptive effect in diabetic mice than in non-diabetic mice. The
      antinociceptive effect of Gosha-jinki-gan (0.3 g/kg, p.o.) in diabetic mice was
      inhibited by administration of either anti-dynorphin antiserum (5 microg, i.t.)
      or nor-binaltorphimine (10 mg/kg, s.c.), a kappa-opioid antagonist. The
      antinociceptive activity of Gosha-jinki-gan (0.3, 1.0 g/kg, p.o.) was decreased
      by excluding processed Aconiti tuber. Furthermore, the antinociceptive effect of
      processed Aconiti tuber (0.03, 0.1 g/kg, p.o.) was also shown to be enhanced in
      diabetic mice. These results suggest that the increased antinociceptive effect of
      Gosha-jinki-gan in diabetic mice is partly derived from the action of processed
      Aconiti tuber and that it is based on stimulation of spinal kappa-opioid
      receptors via dynorphin release. Gosha-jinki-gan was considered useful for
      treating painful diabetic neuropathy.

PMID- 10202854
TI  - A decrease in the amount and function of inhibitory GTP-binding protein in the
      resistance small artery from spontaneously hypertensive rats.
AB  - The inhibitory GTP-binding protein (Gi protein) plays an important role in
      regulation of vascular tone. Many studies have implicated the role of Gi protein
      in conduit vessels. However, the physiological role of Gi protein in the control
      of peripheral microvascular tone in hypertension has not been established yet.
      Therefore, we investigated the concentration of Gi protein in the peripheral
      resistance arteries and aorta in the spontaneously hypertensive rats (SHR),
      normotensive Wistar-Kyoto rats (WKY) and renovascular hypertensive rats (RHR),
      using immunohistochemical methods semiquantitatively. Changes in the function of
      Gi protein in relation to alpha2-adrenoceptor were also investigated by
      microcannulation techniques. We have shown that the amount of alpha2 subunits of
      Gi protein in the cremaster small artery was significantly lower in SHR aged 4
      weeks and older than in age-matched WKY and that there were no significant
      differences between RHR and WKY. We also demonstrated that the function of Gi
      protein in relation to alpha2-adrenoceptor was already lower in SHR before the
      onset of hypertension. The quantitative and functional decline in Gi protein in
      the smooth muscle cells of peripheral small arteries were observed in SHR even
      before the onset of hypertension, whereas rats with secondary hypertension did
      not exhibit this finding.

PMID- 10202853
TI  - Benzodiazepine receptor agonists modulate thymocyte apoptosis through reduction
      of the mitochondrial transmembrane potential.
AB  - Peripheral-type benzodiazepines have been shown to exert immunological effects.
      In this study, we examined the effects of the peripheral-type benzodiazepines on
      murine thymocytes. Murine thymocytes that were incubated with the peripheral-type
      benzodiazepines underwent apoptosis associated with the collapse of mitochondrial
      transmembrane potential (delta psi(m)). The drugs stimulated dexamethasone- and
      etoposide-induced apoptosis with the enhanced collapse of delta psi(m). The
      central-type benzodiazepines had no effect on either the delta psi(m) or
      apoptosis. The reduction of delta psi(m) depended on protein synthesis and
      protein phosphorylation. These results suggest that the immunomodulating effect
      of benzodiazepines is in part due to the modulation of thymocyte apoptosis
      associated with the collapse of delta psi(m).

PMID- 10202855
TI  - Implication of endogenous nitric oxide in gastric mucosal protective effect of T
      593, a novel anti-ulcer agent, in rats.
AB  - The relationship of endogenous nitric oxide (NO) to the gastric mucosal
      protective effect of the novel anti-ulcer agent T-593, (+/-)-(E)-1-[2-hydroxy-2
      (4-hydroxyphenyl)ethyl]-3-[2-[[[5-(methylamino) methyl-2-furyl]methyl]thio]ethyl]
      2-(methylsulfonyl) guanidine, was investigated in rats. T-593 (3-30 mg/kg, p.o.)
      dose dependently prevented the formation of gastric mucosal lesions induced by
      oral administration of aspirin (200 mg/kg) in 0.15 N HCl (HCl-aspirin).
      Pretreatment with N(G)-nitro-L-arginine methylester (L-NAME), a selective
      inhibitor of NO synthase (NOS), attenuated the mucosal protective effect of T
      593. This effect of L-NAME was antagonized by pretreatment with L-arginine, a
      substrate of NOS, but not with D-arginine. Activity of total NOS composed of
      inducible and constitutive NOS in the gastric mucosa was decreased by HCl
      aspirin, and T-593 inhibited this decrease. On the other hand, HCl-aspirin and T
      593 did not affect inducible NOS activity in the gastric mucosa. Furthermore, we
      confirmed that T-593 inhibits the decrease in gastric mucosal blood flow (GMBF)
      induced by HCl-aspirin, and this effect is completely inhibited by pretreatment
      with L-NAME. These results suggest that the mucosal protective effect of T-593 is
      partly mediated by endogenous NO via improvement of GMBF and that a possible
      mechanism for the effect of T-593 is the maintenance of constitutive NOS activity
      in gastric mucosa.

PMID- 10202857
TI  - YM116, 2-(1H-imidazol-4-ylmethyl)-9H-carbazole, decreases adrenal androgen
      synthesis by inhibiting C17-20 lyase activity in NCI-H295 human adrenocortical
      carcinoma cells.
AB  - The concentrations of androstenedione and dehydroepiandrosterone, products of C17
      20 lyase, in the medium after a 6-hr incubation of NCI-H295 cells were decreased
      by YM116 (2-(1H-imidazol-4-ylmethyl)-9H-carbazole) (IC50: 3.6 and 2.1 nM) and
      ketoconazole (IC50: 54.9 and 54.2 nM). 17Alpha-hydroxyprogesterone, a product of
      17alpha-hydroxylase, was increased by YM116 (1-30 nM) and by ketoconazole (10-300
      nM) and then was decreased at higher concentrations of both agents (IC50: 180 nM
      for YM116, 906 nM for ketoconazole), indicating that YM116 and ketoconazole were
      50- and 16.5-fold more specific inhibitors of C17-20 lyase, respectively, than
      17alpha-hydroxylase. Compatible with these findings, progesterone, a substrate of
      17alpha-hydroxylase, was increased by these agents. Cortisol production was
      inhibited by YM116 and ketoconazole (IC50: 50.4 and 80.9 nM, respectively). YM116
      was a 14-fold more potent inhibitor of androstenedione production than cortisol
      production, whereas ketoconazole was a nonselective inhibitor of the production
      of both steroids. YM116 and ketoconazole inhibited the C17-20 lyase activity in
      human testicular microsomes (IC50: 4.2 and 17 nM, respectively). These results
      demonstrate that YM116 reduces the synthesis of adrenal androgens by
      preferentially inhibiting C17-20 lyase activity.

PMID- 10202856
TI  - Identification of SK-951, a novel benzofuran derivative, as an agonist to 5-HT4
      receptors.
AB  - The pharmacological profile of SK-951 ((-)4-amino-N-[2-(1-azabicyclo[3.3.0]octan
      5-yl) ethyl]-5-chloro-2,3-dihydro-2-methylbenzo[b]furan-7-carboxamide
      hemifumarate) was identified in relation to serotonin 5-HT3 and 5-HT4 receptors
      by the receptor binding assay and functional studies. The receptor binding assay
      showed that SK-951 bound to the 5-HT3 receptor with a high affinity, to the 5-HT4
      receptor with relatively higher affinity and to the muscarinic M2 receptor with a
      low affinity, but not to dopamine D1 and D2 and serotonin 5-HT1 and 5-HT2 and
      muscarinic M1 and M3 receptors. SK-951 caused relaxations of tunica muscularis
      mucosae preparations from rat esophagus which were precontracted with carbachol,
      and the effects were antagonized by GR113808, a selective 5-HT4 antagonist. In
      the longitudinal muscle with myenteric plexus (LMMP) preparations from guinea pig
      ileum, SK-951 enhanced the electrically-stimulated contraction of preparations in
      which the 5-HT1, 5-HT2 and 5-HT3 receptors were blocked, and it enhanced the
      electrically-stimulated release of [3H]acetylcholine (ACh). These effects of SK
      951 were antagonized by GR113808. SK-951 inhibited the 5-HT3 receptor-mediated
      contractions. These results indicate that SK-951 possesses properties of an
      agonist for the 5-HT4 receptor and an antagonist for the 5-HT3 receptor. Thus, SK
      951 is a new and potent 5-HT4-receptor agonist and causes contractions of guinea
      pig ileum mediated by enhancement of ACh release via the 5-HT4 receptor.

PMID- 10202859
TI  - Effects of Tyr-MIF-1 on stress-induced analgesia and the blockade of development
      of morphine tolerance by stress in mice.
AB  - The role of Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) in biological responses to stress
      exposure was examined in mice. Intraperitoneal or intracerebroventricular
      administration of Tyr-MIF-1 attenuated not only footshock (FS)- and forced
      swimming (SW)-stress-induced analgesia (SIA) but also socio-psychological (PSY)
      SIA that, when using the communication box, is produced without any direct
      physical nociceptions. Tyr-MIF-1 also disrupted the suppressive effect of
      concurrent exposure to FS- and PSY-stress on the development of morphine
      antinociceptive tolerance. In elevated-plus-maze tests, mice treated with Tyr-MIF
      1 tended to spend more time in the open arms compared with the control group,
      suggesting the anxiolytic properties of the peptide. Thus, the finding that Tyr
      MIF-1 modulates these stress responses suggests that the peptide regulates an
      endogenous biological alert system responding to stress exposure, perhaps,
      counteracting the excessive response of the system. Furthermore, Tyr-MIF-1, in
      the case of PSY-stress, through the attenuation of emotional factors such as fear
      and anxiety, may suppress PSY-SIA and inhibition by PSY-stress of the development
      of morphine tolerance.

PMID- 10202858
TI  - Long-term treatment with angiotensin converting enzyme inhibitor restores reduced
      calcitonin gene-related peptide-containing vasodilator nerve function in
      mesenteric artery of spontaneously hypertensive rats.
AB  - Effects of long-term treatment with angiotensin converting enzyme (ACE) inhibitor
      on decreased function of calcitonin gene-related peptide (CGRP)-containing
      vasodilator nerves (CGRP nerves) in mesenteric resistance artery were
      investigated in spontaneously hypertensive rats (SHR). Eight-week-old SHR were
      treated for 7 weeks with 0.1% captopril, 0.01% temocapril, 0.05% pindolol or
      0.005% hydralazine in drinking water. Long-term treatment with each drug
      significantly lowered mean blood pressure of SHR. In isolated and perfused
      mesenteric vascular beds with active tone, periarterial nerve stimulation (PNS)
      (0.5 to 8 Hz) produced frequency-dependent vasodilations, which were abolished by
      CGRP(8-37) (CGRP-receptor antagonist) and significantly smaller in SHR than in
      normotensive Wistar Kyoto rats. Treatment of SHR with captopril and temocapril
      but not with pindolol and hydralazine resulted in significantly greater PNS
      induced vasodilation than in non-treated SHR, but ACE-inhibitor treatment did not
      affect vasodilation induced by exogenous CGRP. In captopril-treated SHR
      preparations, PNS evoked significantly larger CGRP-like immunoreactive release
      than in non-treated SHR. In non-treated 15-week-old SHR preparations, direct
      perfusion of captopril or temocapril (0.1 microM and 1 microM) did not modify
      frequency-dependent vasodilation in response to PNS. These results suggest that
      long-term ACE inhibitor treatment prevents or restores CGRP nerve function
      reduction in SHR.

PMID- 10202860
TI  - Central injections of capsaicin cause antidiuresis mediated through neurokinin-1
      receptors in rat hypothalamus and vasopressin release.
AB  - Intracerebroventricular injections of capsaicin at 100-500 nmol elicited dose
      dependent decreases in urine outflow volume in anesthetized, hydrated rats. The
      capsaicin (500 nmol)-induced antidiuresis was inhibited by pretreatment with
      CP96345 (30 nmol, a neurokinin-1-receptor antagonist), but not by that with
      phenoxybenzamine (20 nmol, an alpha-adrenoceptor antagonist), timolol (100 nmol,
      a beta-adrenoceptor antagonist) or atropine (300 nmol, a muscarinic antagonist)
      into the hypothalamic supraoptic nucleus (SON). Intravenous injections of d(CH2)5
      D-Tyr(Et)VAVP (50 microg/kg, a vasopressin-receptor antagonist) completely
      blocked the antidiuresis. In intra-SON microdialysis experiments, acetylcholine
      concentration in the perfusate of the capsaicin-injected rats was not different
      from that of the vehicle-injected rats. These findings suggested that capsaicin
      stimulated substance P release in the SON and caused the antidiuresis as a result
      of the increased release of vasopressin into the circulation from the
      neurohypophysis mediated through neurokinin-1 receptors in the SON.

PMID- 10202861
TI  - Depressive state with anxiety in repeated cold-stressed mice in forced swimming
      tests.
AB  - The effects of various types of stress and drugs were studied to assess mouse
      performance in forced swimming tests, following characterization of SART
      (specific alternation of rhythm in environmental temperature) stress. Immobility
      time in the test decreased in mice subjected to SART, acute cold and restraint
      stress. No change was noted due to chronic cold stress or repeated fasting. The
      shortened time did not recover even 24 hr after the end of SART and chronic
      restraint stress. The time in SART-stressed mice finally recovered at 5-7 days.
      Shortening of immobility time in SART-stressed mice was inhibited by diazepam and
      repeated imipramine but not by lithium carbonate. In chronic restraint-stressed
      mice, this time was inhibited by repeated lithium carbonate but not diazepam or
      imipramine. SART stress would thus appear related to anxiety and depression and
      may be useful for detecting new types of antidepressants.

PMID- 10202862
TI  - Effects of exogenous [Arg8]-vasopressin on borderline-hypertensive Hiroshima
      rats.
AB  - The interaction between [Arg8]-vasopressin and a vasopressin receptor antagonist,
      [d(CH2)5(1), O-Me-Tyr2, Arg8]-vasopressin, was examined in Hiroshima rats and
      normotensive control rats under pentobarbital anesthesia. [Arg8]-vasopressin dose
      dependently increased the arterial pressure in both the Hiroshima and control
      rats, the pressor effect being greater in the Hiroshima rats. After the
      administration of a vasopressin antagonist (0.01 mg/kg), which by itself
      decreased arterial pressure only in the Hiroshima rats, the dose-response curve
      for [Arg8]-vasopressin was much more greatly shifted to the right in the control
      rats. These results indicate that with or without a vasopressin antagonist, the
      exogenous [Arg8]-vasopressin induced more powerful pressor actions in the
      Hiroshima rats compared to the control rats.

PMID- 10202863
TI  - The expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) and
      its regulation by ovarian steroids in rat uterine stromal cells.
AB  - The effects of ovarian steroids on the expression of granulocyte-macrophage
      colony-stimulating factor (GM-CSF) in rat uterus were examined. Intense
      expression of GM-CSF mRNA was dispersedly located in the endometrial-myometrial
      junction and stroma of the uterus. GM-CSF was immunohistochemically localized in
      stromal cells and luminal epithelium. Ovariectomy significantly reduced the
      appearance of GM-CSF-mRNA-positive cells and the levels of expression for GM-CSF
      mRNA in the whole uterus, whereas treatment with 17beta-estradiol (E2) or a
      combination of E2 and progesterone (P4) for 5 days on ovariectomized animals
      recruited GM-CSF-mRNA-positive cells and stimulated its expression. The combined
      treatment with E2 and P4 also stimulates the expression for GM-CSF mRNA and the
      production of immunoreactive GM-CSF in the stromal tissues. These data suggest
      that the expression of GM-CSF in uterine stromal cells is partially regulated by
      ovarian steroids.

PMID- 10202864
TI  - Menstrual disorders and infertility caused by inactivating mutations of the
      luteinizing hormone receptor gene.
AB  - OBJECTIVE: To review clinical findings, hormone levels, and DNA analyses in
      genetic males and females with inactivating mutations of the LH receptor gene.
      DESIGN: Review of reported cases. SETTING: A university hospital. PATIENT(S):
      Genetic males and females with inactivating mutations of the LH receptor gene.
      RESULT(S): The clinical presentation in genetic males ranged from female
      genitalia to male genitalia with micropenis caused by Leydig cell hypoplasia.
      Genetic females presented with amenorrhea or oligomenorrhea, enlarged cystic
      ovaries, and infertility. Both males and females had elevated LH levels and
      LH/FSH ratios. Sequencing of genomic DNA revealed homozygous or compound
      heterozygous deletions, nonsense mutations, or missense mutations in the LH
      receptor gene. CONCLUSION(S): This study of patients with inactivating mutations
      of the LH receptor indicates that in genetic males, the action of hCG and LH is
      necessary for the normal development of primary and secondary sexual
      characteristics. In contrast, secondary sexual characteristics develop in genetic
      females in the absence of LH action, but they fail to ovulate.

PMID- 10202865
TI  - Estrogen replacement therapy and breast cancer.

PMID- 10202866
TI  - Establishment of a successful donor embryo program: medical, ethical, and policy
      issues.
AB  - OBJECTIVE: To determine how couples prefer to dispose of their extra embryos and
      to establish a donor embryo program for the treatment of infertile couples.
      DESIGN: Cohort study. SETTING: University-based IVF program. PATIENT(S): Patients
      (n = 365) with cryopreserved embryos in storage for >2 years and eight patients
      who desired donated embryos for transfer. INTERVENTION(S): An IVF ethics
      committee was formed to discuss the ethical and policy issues involved in
      starting an embryo donation program and to establish program guidelines. Couples
      with embryos cryopreserved for > or = 2 years were contacted to determine their
      desires for disposition of embryos. Potential recipients of donated embryos were
      identified in our clinic, and donated embryos were transferred to these patients.
      MAIN OUTCOME MEASURE(S): Desires for embryo disposition and pregnancy rates.
      RESULT(S): Most couples elected either to continue storage of their embryos for
      future use (44%) or to discard their embryos (34%). A minority elected to donate
      their embryos either to infertile couples (11%) or for research (10%). Eight
      couples have had donated embryos transferred, and four have conceived ongoing
      pregnancies. CONCLUSION(S): Although only a small percentage of couples are
      willing to donate their embryos, the resulting number of embryos for use is
      substantial. Transfer of donated embryos results in a high pregnancy rate and is
      a cost-effective treatment of infertility.

PMID- 10202867
TI  - A flexible protocol for artificial preparation of the endometrium without prior
      gonadotropin-releasing hormone agonist suppression in women with functioning
      ovaries undergoing frozen-thawed embryo transfer cycles.
AB  - OBJECTIVE: To present our experience with a flexible and convenient protocol for
      artificial endometrial preparation without prior GnRH agonist suppression in
      patients with functioning ovaries undergoing frozen ET. DESIGN: Case series.
      SETTING: An IVF unit in a university hospital. PATIENT(S): All patients who
      underwent IVF with embryo cryopreservation from December 1997 to June 1998 and
      requested transfer of their frozen-thawed embryos. INTERVENTION(S): Controlled
      endometrial preparation for ET entailed the use of a fixed dose of 6 mg/d of
      micronized E2 started on day 1 of the cycle, followed by concomitant
      administration of micronized P placed in the vagina. MAIN OUTCOME MEASURE(S):
      Hormonal and endometrial profiles throughout the cycle, pregnancy rate per ET,
      implantation rate, and pregnancy outcome. RESULT(S): Of 185 treatment cycles in
      140 patients, 8 cycles (4.3%) were canceled. In another 2 cycles, no embryos were
      suitable for transfer. For the remaining 175 ET cycles, the calculated pregnancy
      rate and implantation rate were 21.7% and 9%, respectively. The proliferative
      phase could be extended up to 20 days but was a mean (+/-SD) of 15+/-1.9 days.
      CONCLUSION(S): For patients with functioning ovaries, controlled endometrial
      preparation for the transfer of frozen-thawed embryos can be done successfully by
      using oral E2 from day 1 of the cycle followed by P preparation. Prior
      suppression with GnRH agonist is not necessary.

PMID- 10202868
TI  - Oral versus intramuscular progesterone for in vitro fertilization: a prospective
      randomized study.
AB  - OBJECTIVE: To evaluate the efficacy of oral micronized progesterone compared with
      IM progesterone in oil for luteal support in patients undergoing IVF who are
      treated with a GnRH agonist. DESIGN: Randomized prospective clinical trial.
      SETTING: University-based IVF center. PATIENT(S): Women <40 years of age who were
      undergoing IVF with luteal GnRH pituitary down-regulation. INTERVENTION(S):
      Patients were randomized to receive either oral micronized progesterone (200 mg
      three times daily) or IM progesterone (50 mg daily). MAIN OUTCOME MEASURE(S):
      Progesterone levels at standardized days 21 and 28, and pregnancy and embryo
      implantation rates. RESULT(S): Day 21 progesterone levels were 77.6+/-13.2 ng/mL
      in the IM group and 81.5+/-16.2 ng/mL in the oral group. Day 28 progesterone
      levels were 76.3+/-15.0 ng/mL in the IM group and 53.6+/-10.1 ng/mL in the oral
      group. The clinical pregnancy rates were 57.9% and 45.8% for the IM and oral
      groups, respectively. The implantation rate per embryo was significantly higher
      in the IM group (40.9%) than in the oral group (18.1%). CONCLUSION(S): When used
      according to our protocols, oral progesterone and IM progesterone result in
      comparable levels of circulating progesterone. However, oral progesterone results
      in a reduced implantation rate per embryo.

PMID- 10202869
TI  - The embryo toxicity of hydrosalpinx fluid is only apparent at high
      concentrations: an in vitro model that stimulates in vivo events.
AB  - OBJECTIVE: To simulate the in vivo model in studying the effect of hydrosalpinx
      fluid on embryonic development. DESIGN: Controlled prospective study. SETTING:
      Academic research center. PATIENT(S): Five hundred eighty-seven two-cell murine
      embryos. INTERVENTION(S): Embryos were grown under two sets of conditions. Half
      were cultured using 10% fetal calf serum in RPM1 medium in varying concentrations
      of hydrosalpinx fluid (0, 1%, 10%, 50%, 75%, and 100%). To more closely mimic the
      in vivo environment, the other half were grown in an endometrial coculture system
      with the same media and hydrosalpinx fluid concentrations. MAIN OUTCOME
      MEASURE(S): Embryonic development. RESULT(S): For each stage of embryogenesis,
      diminished development was noted with increasing concentrations of hydrosalpinx
      fluid. In the group of embryos grown without endometrial coculture, only at a
      minimum concentration of 50% hydrosalpinx fluid was diminished development noted
      for the blastocyst, hatching, and outgrowth stages. When an endometrial coculture
      system was used, development was not inhibited until exposure to a minimum of 75%
      hydrosalpinx fluid. Embryogenesis was enhanced when an endometrial coculture
      system was used for each concentration of hydrosalpinx fluid. CONCLUSION(S): When
      a model is used that more accurately mimics the in vivo conditions of IVF-ET in a
      patient with hydrosalpinges, it appears that high concentrations of hydrosalpinx
      fluid are required to signiticantly impede embryogenesis. The endometrium appears
      to help detoxify hydrosalpinx fluid.

PMID- 10202870
TI  - Fertilization after standard in vitro fertilization versus intracytoplasmic sperm
      injection in subfertile males using sibling oocytes.
AB  - OBJECTIVE: To compare conventional IVF with ICSI in the subfertile male
      population using sibling oocytes. Results from males with isolated severe
      teratozoospermia also are analyzed. DESIGN: Prospective experimental study.
      SETTING: University based IVF clinic. PATIENT(S): Group A: 18 patients with one
      or more abnormalities in count, motility, or morphology. Group B: 20 patients
      with isolated severe teratozoospermia (< or = 4% Kruger Strict Criteria).
      INTERVENTION(S): Ovulation induction, random allocation of sibling oocytes, and
      IVF or ICSI. MAIN OUTCOME MEASURE(S): Fertilization rates (fertilization per
      cycle, fertilization per oocytes, and fertilization per couple) and embryo
      quality. RESULT(S): In group A, fertilization occurred in 13 of 18 (72%) of IVF
      cycles and 17 of 18 (94%) of ICSI cycles. Overall, 69 of 120 (58%) oocytes
      fertilized after IVF, whereas 80 of 131 (61%) fertilized after ICSI. The mean (+/
      SEM) percent of oocytes fertilized per couple was 44.6%+/-9.0% with IVF and
      62.7%+/-5.6% with ICSI (not statistically significant). In group B, fertilization
      occurred in 18 of 20 (90%) cycles after IVF and 20 of 20 (100%) cycles with ICSI.
      Overall, 54 of 113 (48%) of the oocytes fertilized after IVF, whereas 82 of 124
      (66%) fertilized with ICSI. The mean (+/-SEM) percent of oocytes fertilized per
      couple was 50.9%+/-7.1 % with IVF and 66.6%+/-4.7% with ICSI. No statistically
      significant difference in embryo quality after IVF versus ICSI was demonstrated.
      CONCLUSION(S): With severe teratozoospermia, ICSI results in higher fertilization
      rates than conventional IVF, without altering embryo quality. In our subfertile
      male population, there is a trend toward improved fertilization with ICSI, with
      less failed fertilization.

PMID- 10202871
TI  - Prospective randomized double-blind trial of the correlation between time of
      administration and antiestrogenic effects of clomiphene citrate on reproductive
      end organs.
AB  - OBJECTIVE: To investigate whether the timing of administration of clomiphene
      citrate (CC) affects hormone levels, follicular recruitment, reproductive end
      organs, and pregnancy rates. DESIGN: Prospective, randomized, double-blind trial.
      SETTING: Academic center. PATIENT(S): Twenty-three patients with unexplained
      infertility. INTERVENTION(S): Twenty-three patients with unexplained infertility
      underwent 45 cycles of CC and IUI. For each cycle, patients were randomized
      either to receive 100 mg of CC on days 1-5 and placebo on days 5-9 (study group),
      or placebo on days 1-5 and CC on days 5-9 (control group). MAIN OUTCOME
      MEASURE(S): The difference in uterine artery PI, number of follicles, endometrial
      thickness, and pregnancy rates. RESULT(S): Gonadotropins and E2 levels, as well
      as uterine artery pulsatility index, were significantly higher in the study group
      on day 5. In addition, in the study group, a longer time interval existed between
      finishing CC and IUI (8 versus 6 days; MD = 2 days; 95% CI = 1-3) and the
      pregnancy rate was higher than in the control group (6 versus 0; OR = 15.1; 95%
      CI = 1.1-72.4). CONCLUSION(S): Clomiphene citrate commenced on day 1 of the
      menstrual cycle, rather than day 5, results in more rapid follicular growth, a
      longer CC-free period before IUI, and higher pregnancy rates. Although
      methodologically sound, our results should be taken with some degree of caution
      because they are based on a relatively small number of patients.

PMID- 10202872
TI  - Serum concentrations of enclomiphene and zuclomiphene across consecutive cycles
      of clomiphene citrate therapy in anovulatory infertile women.
AB  - OBJECTIVE: To determine the serum concentrations of enclomiphene and zuclomiphene
      across consecutive cycles of clomiphene citrate treatment in anovulatory
      infertile women. DESIGN: Prospective cohort. SETTING: Tertiary institutional
      infertility clinic. PATIENT(S): Fourteen consenting anovulatory infertile women
      receiving standardized, cyclic, incremental treatment with clomiphene citrate for
      ovulation induction. INTERVENTION(S): Clomiphene citrate treatment (50-150 mg/d,
      cycle days 5-9), titrated to the minimum effective ovulation-inducing dose, was
      administered for three to six total cycles. Blood samples were obtained on cycle
      days 3 and 10 in each treatment cycle. MAIN OUTCOME MEASURE(S): Serum
      concentrations of enclomiphene and zuclomiphene. RESULT(S): Cycle day 3
      zuclomiphene levels were below assay limits in all initial cycles, increased
      progressively across three consecutive cycles, and thereafter plateaued. Cycle
      day 3 enclomiphene concentrations were uniformly undetectable. Cycle day 10
      enclomiphene levels increased with dose administered, but these observations were
      not statistically significant. CONCLUSION(S): Clomiphene citrate induction of
      ovulation results in an isomer-specific systemic accumulation of zuclomiphene
      across consecutive cycles of treatment. The combined maximum concentration of
      enclomiphene and zuclomiphene attained in practice approximates 100 nmol/L and is
      generally well below levels previously demonstrated to have adverse effects in
      vitro.

PMID- 10202873
TI  - Pulmonary manifestations of severe ovarian hyperstimulation syndrome: a
      multicenter study.
AB  - OBJECTIVE: To assess the pulmonary manifestations of severe ovarian
      hyperstimulation syndrome (OHSS). DESIGN: A retrospective nationwide 10-year
      multicenter study. SETTING: Sixteen of 19 tertiary medical centers in Israel.
      PATIENT(S): All patients hospitalized at these centers for severe OHSS between
      January 1987 and December 1996. MAIN OUTCOME MEASURE(S): Clinical presentation,
      arterial blood gases on room air, and chest roentgenogram results. RESULT(S): Of
      209 patients, 4% had lobar pneumonia, 2% had adult respiratory distress syndrome
      (ARDS), and 2% had pulmonary thromboembolism. Most patients had dyspnea,
      tachypnea, moderate hypoxemia, increased alveolar-arterial oxygen difference,
      hypocarbia, respiratory alkalosis, and metabolic compensation. The most common
      findings on chest roentgenogram were bilateral elevation of the diaphragm,
      pleural effusion, and pulmonary atelectasis. Patients with pulmonary
      thromboembolism, ARDS, and pneumonia presented with severe hypoxemia and alveolar
      arterial oxygen difference and distinct radiographic findings. CONCLUSION(S):
      Severe OHSS is characterized by an extraparenchymal restrictive type of pulmonary
      dysfunction, attributed to intraabdominal or pleural fluid accumulation, which
      limits descent of the diaphragm and expansion of the thoracic cage. This may
      induce uncoordinated lung ventilation and atelectasis with subsequent ventilation
      perfusion mismatch and hypoxemia. The clinical picture may deteriorate further
      because of pulmonary infection, pulmonary thromboembolism, or ARDS, all of which
      have distinct clinical, radiographic, and blood gas characteristics.

PMID- 10202874
TI  - Pyridostigmine cotreatment for controlled ovarian hyperstimulation in low
      responders undergoing in vitro fertilization-embryo transfer.
AB  - OBJECTIVE: To investigate the effect of pyridostigmine, an acetylcholinesterase
      inhibitor, as cotreatment for controlled ovarian hyperstimulation (COH) in low
      responders. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING:
      A reproductive medicine unit in a university hospital. PATIENT(S): Seventy
      infertile women with a history of low ovarian response to COH using a GnRH
      agonist as part of a long stimulation protocol in previous IVF-ET cycles.
      INTERVENTION(S): Sixty milligrams of pyridostigmine or placebo was administered
      orally twice daily from the first day of COH until the day of hCG injection in
      patients undergoing IVF-ET cycles. MAIN OUTCOME MEASURE(S): In vitro
      fertilization results, pregnancy outcome, and serum and intrafollicular
      concentrations of GH and insulin-like growth factor-1. RESULT(S): Pyridostigmine
      cotreatment was associated with significant decreases in the amount of
      gonadotropins and the duration of stimulation required. The clinical pregnancy
      rate was higher in the pyridostigmine group, but this difference was not
      statistically significant (25.7% vs. 11.4%). The serum GH level on the day of hCG
      injection was significantly higher in the pyridostigmine group than in the
      placebo group. Follicular fluid concentrations of GH and insulin-like growth
      factor-1 were significantly higher in the pyridostigmine group. CONCLUSION(S):
      This study suggests that pyridostigmine cotreatment for COH could affect the
      serum and intrafollicular GH and insulin-like growth factor-1 concentrations and,
      hence, improve the ovarian response to COH and the results of IVF in low
      responders undergoing IVF-ET.

PMID- 10202875
TI  - Decreased inhibin tone and increased activin A secretion characterize
      reproductive aging in women.
AB  - OBJECTIVE: We hypothesized that the increased FSH noted in older reproductive
      aged women is due to both decreased inhibin and increased activin A secretion.
      DESIGN: Comparative clinical study. SETTING: An academic research center.
      PATIENT(S): Five cycling women, aged 43 to 47, were compared to five
      midreproductive women, aged 19 to 38. INTERVENTION(S): Specimens taken every 2 to
      3 days were assayed for inhibin A and B and activin A. MAIN OUTCOME MEASURE(S):
      Integrated concentrations of inhibin A, inhibin B, and activin A in the
      follicular phase, luteal phase, and whole cycle. RESULT(S): Follicular inhibin B
      was reduced in older versus younger women (504 +/-82 versus 748+/-72 total pg).
      Luteal inhibin A was reduced in older versus younger women (668 +/-72 versus
      1152+/-216 total pg). Activin A was elevated throughout the cycle of older versus
      younger women, without within-cycle fluctuations (21+/-2 versus 11+/-1 total ng).
      CONCLUSION(S): Lack of restraint by inhibin A and inhibin B contributes to the
      FSH rise associated with reproductive aging. This loss of restraint occurs in a
      tandem fashion, with inhibin B reduction before ovulation and inhibin A reduction
      after ovulation. Activin A may also play an endocrine role in maintaining
      elevated FSH in older reproductive-aged women.

PMID- 10202876
TI  - Long-term effects of combined hormone replacement therapy on markers of
      endothelial function and inflammatory activity in healthy postmenopausal women.
AB  - OBJECTIVE: To study the effects of combined hormone replacement therapy on
      markers of endothelial function and inflammatory activity. DESIGN: Prospective,
      randomized, controlled study. SETTING: Academic hospital. PATIENT(S): Healthy
      postmenopausal women with an intact uterus. INTERVENTION(S): For the first 12
      months, the hormone replacement therapy group (n = 14) received oral E2, 1 mg
      daily, sequentially combined with 5 or 10 mg of dydrogesterone. Thereafter, they
      received oral E2, 2 mg daily, sequentially combined with 10 mg of dydrogesterone.
      The control group (n = 13) received no treatment. Data were collected at baseline
      and at 3, 12, and 15 months. MAIN OUTCOME MEASURE(S): Parameters of endothelial
      function and inflammatory activity. RESULT(S): During 12 months of follow-up, we
      observed decreases of 15% in plasma levels of endothelin-l, of 21% in soluble
      thrombomodulin, of 14% in von Willebrand factor, and of 12% in clottable
      fibrinogen in the hormone replacement therapy group compared with the control
      group. There was a 5% decrease in soluble E-selectin tevels. All significant
      changes were observed by 3 months and sustained after 15 months. Brachial artery
      flow-mediated vasodilatation and C-reactive protein levels did not change
      significantly. CONCLUSION(S): Long-term combined hormone replacement therapy with
      E2 and dydrogesterone in healthy women was associated with sustained improvement
      in some aspects of endothelial function and in clottable fibrinogen levels.

PMID- 10202877
TI  - Adrenal androgen excess in hyperandrogenism: relation to age and body mass.
AB  - OBJECTIVE: To determine whether DHEAS levels in hyperandrogenic (HA) women retain
      the normal age-related decrease. DESIGN: Prospective study. SETTING: Academic
      tertiary care medical center. PATIENT(S): One hundred forty-five HA patients with
      hirsutism and/or oligo-ovulation and 53 healthy women. INTERVENTION(S): Blood
      samples were obtained on days 3-8 of the menstrual cycle or after an IM
      progesterone-induced withdrawal bleed. MAIN OUTCOME MEASURE(S): Serum samples
      were assayed for progesterone, total testosterone, sex hormone-binding globulin,
      free testosterone, and DHEAS. RESULT(S): Controls and HA patients were similar in
      body mass index and age. A negative correlation between DHEAS levels and age, but
      not body mass index, was found among controls. In HA patients. DHEAS levels
      decreased with age. Dehydroepiandrosterone sulfate levels correlated with the
      hirsutism score in HA patients. When HA patients were subdivided into those with
      low, middle, and high DHEAS levels, those with low DHEAS levels were older and
      weighed more than those with high DHEAS levels. CONCLUSION(S): The negative
      association between DHEAS levels and age is preserved in HA women.
      Hyperandrogenic patients with high DHEAS levels are younger, thinner, and more
      hirsute than those with lower DHEAS levels. These findings suggest that the
      diagnosis of adrenal androgen excess in HA patients may require the use of age
      adjusted normative values.

PMID- 10202878
TI  - Analysis of gonadotropin pulsatility in hirsute women with normal menstrual
      cycles and in women with polycystic ovary syndrome.
AB  - OBJECTIVE: To study the relation between plasma gonadotropin pulsatility,
      androgen levels, and estrogen levels in patients with polycystic ovary syndrome
      (PCOS), in hirsute women with normal menstrual cycles, and in healthy women.
      DESIGN: Prospective study. SETTING: University medical center-based cellular and
      molecular endocrinology laboratory. PATIENT(S): Eight healthy women (group 1), 9
      hirsute women with normal menstrual cycles (group 2), and 19 women with PCOS
      (group 3). INTERVENTION(S): Plasma concentrations of LH and FSH were measured by
      RIA every 15 minutes for 12 hours. MAIN OUTCOME MEASURE(S): Rhythmic parameters
      of 12-hour LH and FSH secretion. RESULT(S): Rhythmic parameters of 12-hour LH
      secretion were significantly higher in patients with PCOS (group 3) than in
      controls (group 1) or in hirsute women with normal menstrual cycles (group 2).
      The frequency of LH pulses was statistically higher in patients with PCOS (group
      3) than in controls (group 1). Statistically significant correlations were found
      when the frequency of LH pulses was plotted against basal LH concentrations and
      rhythmic parameters of 12-hour LH secretion. CONCLUSION(S): Luteinizing hormone
      pulse amplitude was higher in patients with PCOS than in hirsute women with
      normal menstrual cycles or in healthy women. The LH pulse frequency was increased
      only in patients with PCOS compared with healthy women and not in hirsute women
      with normal menstrual cycles.

PMID- 10202879
TI  - Comparison of the sperm quality necessary for successful intrauterine
      insemination with World Health Organization threshold values for normal sperm.
AB  - OBJECTIVE: To compare World Health Organization threshold values for normal sperm
      with the initial sperm quality necessary for successful IUI. DESIGN:
      Retrospective study. SETTING: Private fertility clinic. PATIENT(S): One thousand
      eight hundred forty-one couples undergoing 4,056 cycles of IUI. INTERVENTION(S):
      Intrauterine insemination. MAIN OUTCOME MEASURE(S): Relation of initial sperm
      quality to fecundity. RESULT(S): Progressive motility and total motile sperm
      count were the initial sperm characteristics most closely related to pregnancy on
      discriminant analysis. The per-cycle pregnancy rate averaged 11.1% during the
      first three IUI cycles. Pregnancy rates were > or = 8.2% per cycle when the
      initial sperm values were a concentration of > or = 5 X 10(6)/mL, a total count
      of > or = 10 X 10(6), progressive motility of > or = 30%, or a total motile sperm
      count of > or = 5 x 10(6). Minimal increases in fecundity occurred when initial
      values were greater than these threshold levels. The lowest initial values that
      resulted in pregnancy were a concentration of 2 x 10(6)/mL, a total count of 5 x
      10(6). motility of 17%, and a total motile sperm count of 1.6 X 10(6). Pregnancy
      rates were <3.6% when initial values were between the threshold levels and the
      lowest levels. CONCLUSION(S): The sperm quality that is necessary for successful
      IUI is lower than World Health Organization threshold values for normal sperm.
      Intrauterine insemination is effective therapy for male factor infertility when
      initial sperm motility is > or = 30% and the total motile sperm count is > or = 5
      X 10(6). When initial values are lower, IUI has little chance of success.

PMID- 10202880
TI  - Occupationally related exposures and reduced semen quality: a case-control study.
AB  - OBJECTIVE: To determine whether there is an association between abnormal semen
      parameters and occupational exposures to organic solvents, metals, and
      pesticides. DESIGN: Case-control study using three case groups based on different
      cutoff values for semen parameters and one standard reference group. SETTING:
      University Hospital Utrecht and University Hospital Rotterdam, the Netherlands.
      PATIENT(S): Male partners of couples having their first consultation at the two
      infertility clinics (n = 899). INTERVENTION(S): Men provided at least one semen
      sample. Occupational exposure was assessed with use of job-specific
      questionnaires, a job exposure matrix, and measurements of metals and metabolites
      of solvents in urine. MAIN OUTCOME MEASURE(S): Standard clinical semen analyses
      were used to define case groups and controls. RESULT(S): An association between
      aromatic solvents and reduced semen quality was demonstrated, irrespective of the
      exposure assessment method used. The associations were stronger if the case
      definition was based on stricter cutoff values for semen parameters. Risk
      estimates were higher if the analysis was restricted to primary infertile men.
      Exposure to other pollutants at the workplace was not associated with impaired
      semen quality. CONCLUSION(S): The findings indicated an association between
      aromatic solvent exposure and impaired semen parameters.

PMID- 10202881
TI  - Absence of microdeletions in the Y chromosome in patients with a history of
      cryptorchidism and azoospermia or oligospermia.
AB  - OBJECTIVE: To determine if cryptorchidism is associated with microdeletions of
      interval 6 of the Y chromosome, we evaluated this locus in men with a history of
      cryptorchidism with and without azoospermia or oligospermia and in a control
      group. DESIGN: Clinical study. SETTING: Academic research environment.
      PATIENT(S): Men in whom surgical treatment of cryptorchidism had been performed
      in childhood and healthy control male subjects. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Genotyping of interval 6 of the Y chromosome. RESULT(S):
      Analysis of semen obtained from men treated for cryptorchidism in childhood
      showed azoospermia or oligospermia in 14 of 38 (37%) men. No microdeletions were
      identified with polymerase chain reaction amplification of 17 distinct sequence
      tagged sites located on the long arm of the Y chromosome and the sex determining
      region on Y (SRY) gene. CONCLUSION(S): Microdeletions of interval 6 of the Y
      chromosome were not detected in either the formerly cryptorchid or in the healthy
      subjects. Although we cannot exclude the possibility of point mutations, we
      conclude that cryptorchidism or cryptorchidism associated with azoospermia or
      oligospermia is not due to microdeletions involving interval 6 of the Y
      chromosome.

PMID- 10202883
TI  - Reference values for the midluteal plasma progesterone concentration: evidence
      from human menopausal gonadotropin-stimulated pregnancy cycles.
AB  - OBJECTIVE: To determine reference values for the midluteal plasma progesterone
      concentration. DESIGN: Retrospective analysis. SETTING: Infertility clinic at an
      academic medical center. PATIENT(S): One hundred ninety-two infertile women who
      became pregnant after induction of ovulation with hMG. INTERVENTION(S): The
      plasma progesterone level was measured during the midluteal phase of the hMG
      treatment cycle. MAIN OUTCOME MEASURE(S): The midluteal plasma progesterone
      concentration was correlated with the outcome of the pregnancy. RESULT(S): In
      this cohort of 192 women in whom ovulation was induced with hMG and 5,000 IU of
      hCG, the mean midluteal plasma progesterone concentrations were 29.07 ng/mL,
      25.85 ng/mL, 31.49 ng/mL, 41.39 ng/mL, and 28.64 ng/mL in all cycles that
      resulted in pregnancy, cycles that resulted in full-term singleton pregnancy,
      cycles that resulted in full-term multiple pregnancy, cycles that resulted in
      preterm pregnancy, and cycles that ended in miscarriage, respectively. There was
      no statistically significant difference in the progesterone concentration between
      the cycles that resulted in full-term pregnancy and those that ended in
      miscarriage, but there was a statistically significant difference between the
      cycles that resulted in singleton pregnancy and those that resulted in multiple
      pregnancy. The minimum value that was compatible with a full-term pregnancy in
      this cohort of women was 10.83 ng/mL. CONCLUSION(S): In a cohort of 192 women,
      the minimum plasma progesterone concentration on day 7 in women who attained a
      full-term pregnancy after induction of ovulation with 5,000 IU of hCG was 10.83
      ng/mL.

PMID- 10202882
TI  - Genetic influences on endometriosis in an Australian twin sample.
      sueT@qimr.edu.au.
AB  - OBJECTIVE: To investigate the prevalence of and twin pair concordance for
      endometriosis. DESIGN: A questionnaire survey incorporating validation. SETTING:
      An Australia-wide volunteer sample of female monozygotic (MZ) and dizygotic (DZ)
      twin pairs from the Australian National Health and Medical Research Council Twin
      Register. PATIENT(S): Twins were selected only on the basis of previous
      participation in twin research. INTERVENTION(S): Questionnaires were sent to
      3,298 individuals. Information was requested from physicians named by consenting
      twins. MAIN OUTCOME MEASURE(S): Reported endometriosis, validated where possible
      by pathology or surgical report. RESULT(S): Three thousand ninety-six (94%) of
      the twins and 145 (82%) of the physicians responded to the survey. Two hundred
      fifteen twins reported endometriosis, for a prevalence rate of .07 among question
      respondents. Tetrachoric twin pair correlations for self-reported endometriosis
      (MZ: n = 854 and DZ: n = 493) were rMz = .46+/-.09 and rDz = .28 +/-.13. When
      available medical and pathology reports were included, they changed to rMz =.52
      +/-.08 and rDZ = .19+/-.16, suggesting that 51% of the variance of the latent
      liability to endometriosis may be attributable to additive genetic influences.
      CONCLUSION(S): These findings support the hypothesis that genes influence
      liability to endometriosis.

PMID- 10202885
TI  - The first polar body does not predict accurately the location of the metaphase II
      meiotic spindle in mammalian oocytes.
AB  - OBJECTIVE: To evaluate how well polar body location predicts spindle localization
      and to examine spindle morphology. DESIGN: Randomized, controlled animal study.
      SETTING: University-affiliated research laboratory. ANIMAL(S): Mature, female
      golden hamsters. INTERVENTION(S): After superovulation with pregnant mare serum
      gonadotropin and hCG, metaphase II oocytes were obtained and imaged under digital
      polarization microscopy. MAIN OUTCOME MEASURE(S): Identify the meiotic spindle in
      living, unfixed hamster oocytes and determine spindle location relative to the
      polar body. RESULT(S): Spindles were imaged in 30 oocytes and only in 5 of them
      could the polar body predict the spindle localization. In the remaining oocytes,
      the spindles presented a random distribution within the cytoplasm. CONCLUSION(S):
      These data show that the polar body location is not an accurate predictor for
      meiotic spindle location in mammalian oocytes.

PMID- 10202884
TI  - Elevated day 3 serum follicle stimulating hormone and/or estradiol may predict
      fetal aneuploidy.
AB  - OBJECTIVE: To determine whether baseline serum FSH and/or E2 concentrations can
      predict the risk for fetal chromosomal abnormalities. DESIGN: Case control study.
      SETTING: Reproductive technology program at a university hospital. PATIENT(S):
      Patients who underwent dilation and curettage (D + C), and whose products of
      conception were karyotyped. INTERVENTION(S): Patients underwent natural
      conception or controlled ovarian hyperstimulation followed by intrauterine
      insemination, in vitro fertilization and embryo transfer, gamete intrafallopian
      transfer, or zygote intrafallopian transfer. MAIN OUTCOME MEASURE(S): Baseline
      serum FSH and E2 concentrations and fetal karyotype. RESULT(S): Genetic
      evaluation of 78 D + C specimens revealed 34 normal and 44 abnormal fetal
      karyotypes. A significantly greater proportion of women with abnormal fetal
      karyotype had elevated baseline serum FSH (> or =15 mIU/mL [RIA] or 10 mIU/mL
      [Immulite]) and/or E2 > or = 50 pg/mL [Immulite]) compared with women of normal
      fetal karyotype. Among karyotypically abnormal abortuses, autosomal trisomy was
      the most common abnormality noted (79.5%), followed by mosaicism (6.8%),
      triploidy (6.8%), monosomy XO (4.5%), and balanced translocation (2.3%).
      CONCLUSION(S): Baseline serum FSH and/or E2 concentrations may be valuable as
      predictors of fetal aneuploidy.

PMID- 10202886
TI  - Recombinant human leukemia inhibitory factor enhances the development of
      preimplantation mouse embryo in vitro.
AB  - OBJECTIVE: To assess the effect of recombinant human leukemia inhibitory factor
      (rhLIF) on mouse embryos in vitro. DESIGN: Controlled prospective study. SETTING:
      Academic research environment. ANIMAL(S): Female CB6F1 mice between 6 and 8 weeks
      old. INTERVENTION(S): Mice were divided randomly into three groups, which
      included a control group in an in vivo study (group I) and two groups in an in
      vitro study (groups II and III). Mice were killed at 116-120 hours (group I) and
      44-48 hours (groups II and III) after hCG injection. Two-cell embryos (groups II
      and III) and blastocysts (group I) were obtained. Embryos in group II were
      cocultured with human tubal fluid (HTF) + 0.5% human serum albumin and in group
      III with HTF + rhLIF (1,000 U/mL) under paraffin oil. MAIN OUTCOME MEASURE(S):
      The embryonic numbers in different stages were recorded and compared. RESULT(S):
      Similar early embryo development to the four- to eight-cell and morula stages was
      noted between groups II and III (87.3% versus 91.0% and 74.6% versus 87.1%,
      respectively). However, further embryo development to the blastocyst, expanded
      blastocyst, and hatching blastocyst in group II (48.1%, 31.7%, and 18.5%,
      respectively) was lower than that in group III (83.6%, 53.7%, and 37.8%).
      CONCLUSION(S): RhLIF does not provide obvious stimulation in the early mouse
      embryo. However, rhLIF has positive effects on preimplantation blastocyst growth,
      differentiation, and hatching.

PMID- 10202887
TI  - In vitro maturation of human preovulatory oocytes reconstructed by germinal
      vesicle transfer.
AB  - OBJECTIVE: To describe a micromanipulation-electrofusion procedure for
      transferring germinal vesicles (GVs) between immature human oocytes. DESIGN:
      Pilot study to assess oocyte maturation after an invasive micromanipulation
      procedure. SETTING: Research laboratory at a university medical center.
      PATIENT(S): Immature oocytes were discarded from intracytoplasmic sperm injection
      (ICSI)-IVF cycles of patients 23-48 years of age. INTERVENTION(S): Initially, GV
      removal and transfer were performed on the same oocyte; these "self
      reconstructed" oocytes were then cultured in vitro for up to 50 hours and
      examined periodically for maturation as judged by the extrusion of the first
      polar body. In a second study, GVs from oocytes of "old" patients (>38 years old)
      were successfully transferred into enucleated immature oocytes of "young"
      patients (<31 years old). MAIN OUTCOME MEASURE(S): Extrusion of the first polar
      body was monitored in "reconstructed" and control oocytes; karyotypes also were
      analyzed at meiosis II. RESULT(S): From 48 oocytes from old patients, 12 GVs were
      successfully removed, transferred, and fused into previously enucleated oocytes
      from young patients. After in vitro culture, 7 of these "reconstructed" oocytes
      matured to meiosis II, a maturation rate not significantly different from that
      observed in nonmanipulated controls. A normal, second meiotic metaphase
      chromosome complement was observed in 4 of 5 reconstructed oocytes.
      CONCLUSION(S): Normal meiosis can occur after the transfer of a GV into an
      enucleated host oocyte. Germinal vesicle transfer may be a valuable research
      procedure that generates cell models to characterize the cytoplasmic-nuclear
      interplay for cell cycle regulation, maturation, and fertilization in the human
      oocyte; it also may be a potentially attractive alternative to oocyte donation.

PMID- 10202889
TI  - Temporal expression of the transgenic human protamine gene cluster.
AB  - OBJECTIVE: To ascertain the fidelity of expression of the genes from the
      transgenic human sperm-specific nuclear packaging protamine-1-->protamine-2-
      >transition protein-2 (PRM1-->PRM2-->TNP2) locus. DESIGN: Controlled human
      transgene study. SETTING: Basic science laboratory. ANIMAL(S): Age-matched
      transgenic and nontransgenic mice. INTERVENTION(S): Transgenic mice containing
      the human protamine locus were mated. One testis from each offspring was frozen
      at -80 degrees C and the other was preserved in formalin. MAIN OUTCOME
      MEASURE(S): The temporal expression of the human and mouse protamines was
      evaluated by Northern blot analysis. Orientation of the transgenic locus was
      determined by Southern blot analysis. Tissue morphology was assessed
      histologically. RESULT(S): Conservation of transgenic morphology was confirmed.
      Head-to-tail integration of the PRM1--> PRM2-->TNP2 locus was shown. Temporal
      expression of the mouse and human protamine genes was maintained in the
      transgenic state. CONCLUSION(S): These results show that the head-to-tail
      concatomer of the PRMI-->PRM2-->TNP2 locus contains all the necessary elements
      for appropriate temporal expression while maintaining testicular structure and
      function.

PMID- 10202888
TI  - Keratinocyte growth factor promotes the survival, growth, and differentiation of
      preantral ovarian follicles.
AB  - OBJECTIVE: To determine the effect of treatment with keratinocyte growth factor
      (KGF) on the survival of cells in cultured preantral follicles and on the growth
      and differentiation of preantral follicles. DESIGN: Preantral follicles (140-150
      microm) were dissected mechanically from the ovaries of 14-day-old rats and
      cultured for 24 hours with and without KGF. Genomic DNA was extracted, labeled
      with [32P]-dideoxyadenosine triphosphate, and fractionated through agarose gels.
      For growth studies, the follicles were cultured individually in 96-well dishes.
      After 72 hours, the follicles were collected and their protein or DNA content was
      evaluated and their inhibin-alpha content was determined. RESULT(S): Keratinocyte
      growth factor suppressed apoptosis in cultured preantral follicles by 60%.
      Treatment with KGF or FSH increased follicle diameter by 8% and 16%,
      respectively, and combined treatment with KGF and FSH increased follicle diameter
      by 26%. Western blot analysis demonstrated increased expression of inhibin-alpha
      content after treatment with KGF (2-fold), treatment with FSH (4-fold), and
      combined treatment with FSH and KGF (12-fold), demonstrating the effect of KGF on
      preantral follicle differentiation. CONCLUSION(S): Treatment with KGF promotes
      the survival, growth, and differentiation of cultured preantral follicles.
      Keratinocyte growth factor produced by theca cells may play a role in the
      progression of early follicle development.

PMID- 10202890
TI  - Microdeletion of the DAZ (deleted in azoospermia) gene or the YRRM (Y chromosome
      ribonucleic acid recognition motif) gene does not occur in patients with
      Klinefelter's syndrome with and without spermatogenesis.
AB  - OBJECTIVE: To evaluate the occurrence of microdeletions of the Y chromosome
      involving the DAZ and YRRM genes in patients with Klinefelter's syndrome with and
      without spermatogenesis. DESIGN: Controlled clinical study. SETTING: Yamagata
      University Hospital, Yamagata, Japan. PATIENT(S): Patients with Klinefelter's
      syndrome with spermatogenesis (n = 1) and without spermatogenesis (n = 20) and a
      control group of men of proven fertility (n = 10). INTERVENTION(S): Blood and
      semen sampling and testicular biopsy. MAIN OUTCOME MEASURE(S): Semen analysis,
      polymerase chain reaction amplification of 32 DNA loci on the long arm of the Y
      chromosome involving the DAZ (deleted in azoospermia) and YRRM (Y chromosome
      ribonucleic acid recognition motif) genes, and measurement of plasma FSH, LH, and
      testosterone levels. RESULT(S): No microdeletions of 32 loci were found in any of
      the patients with Klinefelter's syndrome, either with or without spermatogenesis.
      Plasma LH and FSH levels were abnormally high and testosterone levels were
      reduced in all the patients with Klinefelter's syndrome. American Society for
      Reproductive Medicine.) CONCLUSION(S): Severe impairment of spermatogenesis in
      patients with Klinefelter's syndrome is not caused by microdeletions of the Y
      chromosome involving the DAZ and YRRM genes.

PMID- 10202891
TI  - Sibling embryo blastocyst development correlates with the in vitro fertilization
      day 3 embryo transfer pregnancy rate in patients under age 40.
AB  - OBJECTIVE: To examine the IVF day 3-ET pregnancy rate in patients under 40 with
      sibling embryo blastocyst development, compared with similar patients without
      blastocyst formation. DESIGN: Retrospective analysis. SETTING: Academic
      infertility center. PATIENT(S): One hundred twenty-five IVF day 3-ET patients
      under 40 with sibling embryos for extended culture. INTERVENTION(S): Extended
      culture of nontransferred sibling embryos for blastocyst development. MAIN
      OUTCOME MEASURE(S): Pregnancy and multiple gestation rates, number of oocytes,
      embryos formed, and embryos transferred. RESULT(S): Thirty-eight percent of
      patients became pregnant. Forty-eight percent of patients had sibling embryos
      develop to blastocyst. The blastocyst group had more oocytes retrieved (17.4+/
      6.6 versus 14.4+/-5.6), more embryos formed (11.2+/-4.2 versus 8.8+/-3.2), and a
      higher clinical pregnancy rate (60% versus 18%) than the group without blastocyst
      development. CONCLUSION(S): Blastocyst transfer has been shown to improve
      implantation rates and reduce the risk of multiple gestations from assisted
      reproductive technology. Sibling embryo blastocyst development may reflect
      superior embryo quality, as manifested by increased IVF-ET pregnancy rates. In
      addition to predicting pregnancy in the current cycle, sibling embryo blastocyst
      development may provide information about the potential for fresh blastocyst
      transfer in subsequent cycles and help to identify patients at risk for multiple
      gestations.

PMID- 10202892
TI  - In vitro fertilization and intracytoplasmic sperm injection pregnancies after
      successful transport of oocytes by airplane.
AB  - OBJECTIVE: To determine the feasibility of a transport IVF program involving air
      transportation of oocytes. DESIGN: Prospective cohort study. SETTING: Regional
      hospital (Hopital de Chicoutimi) and University Infertility Center (McGill
      Reproductive Center, Montreal). PATIENT(S): The first series of patients referred
      for IVF or IVF and ICSI, for a variety of indications, who opted for inclusion in
      the transport IVF program. INTERVENTION(S): The IVF-ET with ovarian stimulation
      and oocyte collection at the peripheral unit and transport of the oocytes by
      airplane to the McGill Reproductive Center where IVF or ICSI was performed. MAIN
      OUTCOME MEASURE(S): Clinical pregnancy. RESULT(S): Seven couples, in the first
      series, underwent nine cycles of transport IVF treatment. Two also underwent
      ICSI. There were two clinical pregnancies. CONCLUSION(S): Transport IVF using air
      travel is possible and opens the possibility for this type of program to be
      implemented in large countries with scattered populations, such as the United
      States, Canada, and Australia.

PMID- 10202893
TI  - A percutaneous large-needle aspiration biopsy technique for histologic
      examination of the testis in infertile patients.
AB  - OBJECTIVE: To describe a relatively new percutaneous large-needle aspiration
      biopsy technique for histologic examination of the testis in infertile patients.
      DESIGN: Retrospective analysis of clinical and pathologic data. SETTING: Clinical
      and academic research environment. PATIENT(S): Sixty-six infertile patients who
      underwent testicular biopsy. INTERVENTION(S): Local anesthesia was induced
      through spermatic cord block with lidocaine, and a relatively large needle
      (usually 18- or 20-gauge) was introduced percutaneously into the testicle without
      a scrotal incision. MAIN OUTCOME MEASURE(S): The number of seminiferous tubules
      per histologic section of each testicular biopsy sample. RESULT(S): A mean of 74
      seminiferous tubules were obtained in the histologic sections of each biopsy
      sample. This number varied according to the size of the needle used; it was 24.7
      when a 21-gauge needle was used, 56.2 when a 20-gauge needle was used, and 103
      when an 18-gauge needle was used. The biopsies were performed in the office. No
      significant hematomas occurred, no antibiotic prophylaxis was prescribed, and no
      postbiopsy medical or pharmacologic interventions were required. CONCLUSION(S):
      Tissue specimens as large as those obtained with open surgical biopsy can be
      obtained from the testicles of infertile patients with the use of a percutaneous
      technique that is easier, less costly, and safer than any previously reported.

PMID- 10202894
TI  - Evaluation of the SQA IIB: a new version of a sperm quality analyzer.
AB  - OBJECTIVE: To evaluate the SQA IIB (Sperm Quality Analyzer; MES-Medical
      Electronic Systems, Migdal Haemek, Israel), sperm analyzer that claims to read
      the three main sperm indices through algorithmic means and without a microscope.
      DESIGN: Controlled laboratory study comparing two methods of sperm analysis.
      SETTING: Academic environment. PATIENT(S): Twenty-six healthy volunteers.
      INTERVENTION(S): Samples from intact or manipulated specimens were analyzed with
      the standards of the World Health Organization and the SQA IIB. MAIN OUTCOME
      MEASURE(S): Results by the two methods were compared and evaluated statistically.
      RESULT(S): Values from the SQA IIB deviated significantly from those obtained by
      the standard method for all three indices. Disagreement was more than twofold in
      53% and more than threefold in 33% of cases. In specimens with <8% motility or
      total lack of motility, the SQA IIB showed zero concentration, zero motility, and
      no normal forms. CONCLUSION(S): Analysis of the three main sperm indices by the
      SQA IIB is of limited accuracy and reliability. The principle of an indirect
      evaluation through algorithmic means is inadequate. Because it may furnish
      misleading information, which is sometimes crucial for the treated couple, it is
      not suitable for screening and cannot be recommended for clinics, sperm banks, or
      research studies in andrology.

PMID- 10202895
TI  - Computer-controlled bipolar endotubal sterilization is successful in a rabbit
      model.
AB  - OBJECTIVE: To determine the efficacy of a computer-controlled bipolar endotubal
      catheter system designed to accomplish safe, effective, and inexpensive female
      sterilization in preventing pregnancy in a rabbit model. DESIGN: Prospective
      controlled study. SETTING: University animal care facility. ANIMAL(S): Sixty
      healthy virginal female New Zealand white rabbits. INTERVENTION(S): Rabbits were
      assigned to the following groups: [1] endotubal radiofrequency minimal energy (95
      degrees C) treatment; [2] endotubal radiofrequency maximal energy (105 degrees C)
      treatment; [3] endouterine radiofrequency (105 degrees C) treatment; [4]
      nonsurgical control; [5] laparotomy-only control; [6] endotubal radio-frequency
      sham control; and [7] external Kleppinger forceps bipolar cautery control.
      Rabbits were mated at 4 or 12 weeks after treatment. MAIN OUTCOME MEASURE(S):
      Pregnancy outcomes in treated animals and nontreated controls. RESULT(S): No
      pregnancies were observed in any of the uterine horns in which minimal or maximal
      energy was delivered to the fallopian tubes or uterus, although pregnancy
      occurred in one horn as a result of the delivery of energy below the
      radiofrequency minimum of 95 degrees C. The outcomes of the treatment groups were
      significantly different from those of the nonsurgical and sham surgical control
      groups. CONCLUSION(S): With adequate tissue heating, 100% sterilization efficacy
      was achieved with a new, computer-controlled bipolar catheter, whereas
      pregnancies occurred in all untreated control groups. If human studies support
      these results, the goal of a safe, effective means of transcervical sterilization
      may be realized.

PMID- 10202896
TI  - Differences between crossover and parallel study designs--debate?

PMID- 10202897
TI  - Trying to preserve ovarian function in the face of chemotherapy?

PMID- 10202898
TI  - Environmental toxicants and sex ratios--effects?

PMID- 10202899
TI  - Relief of pain and/or spasm during diagnostic hysteroscopy?

PMID- 10202900
TI  - Endometriosis--back to basics with the physical examination?

PMID- 10202901
TI  - Variables in the fractioning of human seminal fluid!

PMID- 10202902
TI  - Treatment alternatives for retro-grade ejaculation.

PMID- 10202903
TI  - Delivering science to the public.

PMID- 10202904
TI  - Antibiotic resistance--to treat...

PMID- 10202905
TI  - . . . or not to treat?

PMID- 10202906
TI  - Gene expression in space.

PMID- 10202909
TI  - NIH appoints a director for its AIDS vaccine center.

PMID- 10202908
TI  - . . . While Canada faces the issue head-on.

PMID- 10202907
TI  - Spanish researchers reject xeno moratorium...

PMID- 10202911
TI  - Group calls for big increase in diabetes research.

PMID- 10202910
TI  - Italian government rebuffs emerging biotechnology industry.

PMID- 10202912
TI  - Finding funding for China's HIV research.

PMID- 10202913
TI  - Japan reorganizes national biomedical research groups.

PMID- 10202914
TI  - Scientists bemoan lack of finances for new center.

PMID- 10202916
TI  - The South African Medical Research Council: Africanizing health research.

PMID- 10202915
TI  - Stem cell debate heats up as guidelines are prepared.

PMID- 10202917
TI  - Surviving Ebola virus infection.

PMID- 10202918
TI  - Mahogany adds color to the evolving story of body weight regulation.

PMID- 10202919
TI  - Anti-sunshine vitamin A.

PMID- 10202920
TI  - Widening perspectives of intracytoplasmic sperm injection.

PMID- 10202921
TI  - For Pseudomonas aeruginosa, stealth is no longer enough.

PMID- 10202922
TI  - Gene therapy for peanut allergy.

PMID- 10202923
TI  - Receptor seeks ligand: on the way to cloning the molecular receptors for sweet
      and bitter taste.

PMID- 10202924
TI  - Variation on a trinucleotide theme.

PMID- 10202925
TI  - The 1918 'Spanish' flu: pearls from swine?

PMID- 10202926
TI  - Oral gene delivery with chitosan--DNA nanoparticles generates immunologic
      protection in a murine model of peanut allergy.
AB  - Food allergy is a common and often fatal disease with no effective treatment. We
      describe here a new immunoprophylactic strategy using oral allergen-gene
      immunization to modulate peanut antigen-induced murine anaphylactic responses.
      Oral administration of DNA nanoparticles synthesized by complexing plasmid DNA
      with chitosan, a natural biocompatible polysaccharide, resulted in transduced
      gene expression in the intestinal epithelium. Mice receiving nanoparticles
      containing a dominant peanut allergen gene (pCMVArah2) produced secretory IgA and
      serum IgG2a. Compared with non-immunized mice or mice treated with 'naked' DNA,
      mice immunized with nanoparticles showed a substantial reduction in allergen
      induced anaphylaxis associated with reduced levels of IgE, plasma histamine and
      vascular leakage. These results demonstrate that oral allergen-gene immunization
      with chitosan-DNA nanoparticles is effective in modulating murine anaphylactic
      responses, and indicate its prophylactic utility in treating food allergy.

PMID- 10202927
TI  - Active and passive immunization with the Pseudomonas V antigen protects against
      type III intoxication and lung injury.
AB  - Pseudomonas aeruginosa is an opportunistic bacterial pathogen that can cause
      fatal acute lung infections in critically ill individuals. Damage to the lung
      epithelium is associated with the expression of toxins that are directly injected
      into eukaryotic cells through a type Ill-mediated secretion and translocation
      mechanism. Here we show that the P. aeruginosa homolog of the Yersinia V antigen,
      PcrV, is involved in the translocation of type III toxins. Vaccination against
      PcrV ensured the survival of challenged mice and decreased lung inflammation and
      injury. Antibodies to PcrV inhibited the translocation of type III toxins.

PMID- 10202928
TI  - Antagonism of cytotoxic T-lymphocyte activation by soluble CD8.
AB  - The CD8 co-receptor is important in the differentiation and selection of class I
      MHC-restricted T cells during thymic development, and in the activation of mature
      T lymphocytes in response to antigen. Here we show that soluble CD8alphaalpha
      receptor, despite an extremely low affinity for MHC, inhibits activation of
      cytotoxic lymphocytes by obstructing CD3 zeta-chain phosphorylation. We propose a
      model for this effect that involves interference of productive receptor
      multimerization at the T-cell surface. These results provide new insights into
      the mechanism of T-cell activation and evidence that CD8 function is exquisitely
      sensitive to disruption, an effect that might be exploited by molecular
      therapeutics.

PMID- 10202929
TI  - Dendritic cells directly trigger NK cell functions: cross-talk relevant in innate
      anti-tumor immune responses in vivo.
AB  - Cytotoxic T lymphocytes and natural killer cells are essential effectors of anti
      tumor immune responses in vivo. Dendritic cells (DC) 'prime' tumor antigen
      specific cytotoxic T lymphocytes; thus, we investigated whether DC might also
      trigger the innate, NK cell-mediated anti-tumor immunity. In mice with MHC class
      I-negative tumors, adoptively transferred- or Flt3 ligand-expanded DC promoted NK
      cell-dependent anti-tumor effects. In vitro studies demonstrated a cell-to-cell
      contact between DC and resting NK cells that resulted in a substantial increase
      in both NK cell cytolytic activity and IFN-gamma production. Thus, DC are
      involved in the interaction between innate and adaptive immune responses.

PMID- 10202930
TI  - Control of inducible chemoresistance: enhanced anti-tumor therapy through
      increased apoptosis by inhibition of NF-kappaB.
AB  - Programmed cell death (apoptosis) seems to be the principal mechanism whereby
      anti-oncogenic therapies such as chemotherapy and radiation effect their
      responses. Resistance to apoptosis, therefore, is probably a principal mechanism
      whereby tumors are able to overcome these cancer therapies. The transcription
      factor NF-kappaB is activated by chemotherapy and by irradiation in some cancer
      cell lines. Furthermore, inhibition of NF-kappaB in vitro leads to enhanced
      apoptosis in response to a variety of different stimuli. We show here that
      inhibition of NF-kappaB through the adenoviral delivery of a modified form of
      IkappaBalpha, the inhibitor of NF-kappaB, sensitizes chemoresistant tumors to the
      apoptotic potential of TNFalpha and of the chemotherapeutic compound CPT-11,
      resulting in tumor regression. These results demonstrate that the activation of
      NF-kappaB in response to chemotherapy is a principal mechanism of inducible tumor
      chemoresistance, and establish the inhibition of NF-kappaB as a new approach to
      adjuvant therapy in cancer treatment.

PMID- 10202931
TI  - Ultraviolet irradiation of human skin causes functional vitamin A deficiency,
      preventable by all-trans retinoic acid pre-treatment.
AB  - We report here that ultraviolet irradiation substantially reduced the mRNA and
      protein of the two major nuclear retinoid receptors, RAR-gamma and RXR-alpha, in
      human skin in vivo. Pre-treatment with retinoic acid mitigated this loss of
      nuclear retinoid receptors. Ultraviolet irradiation caused a near-total loss of
      retinoic acid induction of two RAR/RXR target genes, cellular retinoic acid
      binding protein-II and RA 4-hydroxylase, but did not affect 1,25-dihydroxyvitamin
      D3 induction of the vitamin D receptor/RXR-regulated gene vitamin D 24
      hydroxylase. In effect, ultraviolet irradiation causes a functional vitamin A
      deficiency that may have deleterious effects on skin function, contributing to
      skin photo-aging and carcinogenesis.

PMID- 10202932
TI  - Defective humoral responses and extensive intravascular apoptosis are associated
      with fatal outcome in Ebola virus-infected patients.
AB  - Ebola virus is very pathogenic in humans. It induces an acute hemorrhagic fever
      that leads to death in about 70% of patients. We compared the immune responses of
      patients who died from Ebola virus disease with those who survived during two
      large outbreaks in 1996 in Gabon. In survivors, early and increasing levels of
      IgG, directed mainly against the nucleoprotein and the 40-kDa viral protein, were
      followed by clearance of circulating viral antigen and activation of cytotoxic T
      cells, which was indicated by the upregulation of FasL, perforin, CD28 and gamma
      interferon mRNA in peripheral blood mononuclear cells. In contrast, fatal
      infection was characterized by impaired humoral responses, with absent specific
      IgG and barely detectable IgM. Early activation of T cells, indicated by mRNA
      patterns in peripheral blood mononuclear cells and considerable release of gamma
      interferon in plasma, was followed in the days preceding death by the
      disappearance of T cell-related mRNA (including CD3 and CD8). DNA fragmentation
      in blood leukocytes and release of 41/7 nuclear matrix protein in plasma
      indicated that massive intravascular apoptosis proceeded relentlessly during the
      last 5 days of life. Thus, events very early in Ebola virus infection determine
      the control of viral replication and recovery or catastrophic illness and death.

PMID- 10202933
TI  - Fetal immunization of baboons induces a fetal-specific antibody response.
AB  - Neonates face a high risk of infection because of the immaturity of their immune
      systems. Although the transplacental transfer of maternal antibodies to the fetus
      may convey improved postnatal immunity, this transfer occurs late in gestation
      and may fail to prevent in utero infection. Both fetal immunization and in utero
      exposure to antigen can result in a state of immunologic tolerance in the
      neonate. Tolerance induction of fetal and premature infant lymphocytes has become
      a paradigm for neonatal responsiveness. However, fetal IgM responses have been
      demonstrated to maternal immunization with tetanus toxoid and to congenital
      infections such as rubella, toxoplasma, cytomegalovirus and human
      immunodeficiency virus. Moreover, 1-week-old infants can respond to standard
      pediatric vaccination, and neonates immunized with polysaccharide antigens do not
      develop immunologic tolerance. Here, direct immunization of the baboon fetus with
      recombinant hepatitis B surface antigen produced a specific fetal IgG antibody
      response. No specific maternal antibody response was detected, eliminating the
      possibility of vertical antibody transmission to the fetus. Some infants also
      responded to later vaccinations with hepatitis B surface antigen, indicating that
      no immunological tolerance was induced by prior fetal immunization. These results
      characterize the ability of the fetal immune system to respond to in utero
      vaccination. We demonstrate that active fetal immunization can serve as a safe
      and efficient vaccination strategy for the fetus and neonate.

PMID- 10202934
TI  - Unique checkpoints during the first cell cycle of fertilization after
      intracytoplasmic sperm injection in rhesus monkeys.
AB  - Intracytoplasmic sperm injection has begun an era of considerable improvements in
      treating male infertility. Despite its success, questions remain about the
      dangers of transmitting traits responsible for male infertility, sex and
      autosomal chromosome aberrations and possible mental, physical and reproductive
      abnormalities. We report here the first births of rhesus monkeys produced by
      intracytoplasmic sperm injection at rates greater or equal to those reported by
      clinics. Essential assumptions about this process are flawed, as shown by results
      with the preclinical, nonhuman primate model and with clinically discarded
      specimens. Dynamic imaging demonstrated the variable position of the second
      meiotic spindle in relation to the first polar body; consequently, microinjection
      targeting is imprecise and potentially lethal. Intracytoplasmic sperm injection
      resulted in abnormal sperm decondensation, with the unusual retention of vesicle
      associated membrane protein and the perinuclear theca, and the exclusion of the
      nuclear mitotic apparatus from the decondensing sperm nuclear apex. Male
      pronuclear remodeling in the injected oocytes was required before replication of
      either parental genome, indicating a unique G1-to-S transition checkpoint during
      zygotic interphase (the first cell cycle). These irregularities indicate that the
      intracytoplasmic sperm injection itself might lead to the observed increased
      chromosome anomalies.

PMID- 10202935
TI  - Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial
      progenitor cells for neovascularization.
AB  - Endothelial progenitor cells (EPCs) have been isolated from circulating
      mononuclear cells in human peripheral blood and shown to be incorporated into
      foci of neovascularization, consistent with postnatal vasculogenesis. We
      determined whether endogenous stimuli (tissue ischemia) and exogenous cytokine
      therapy (granulocyte macrophage-colony stimulating factor, GM-CSF) mobilize EPCs
      and thereby contribute to neovascularization of ischemic tissues. The development
      of regional ischemia in both mice and rabbits increased the frequency of
      circulating EPCs. In mice, the effect of ischemia-induced EPC mobilization was
      demonstrated by enhanced ocular neovascularization after cornea micropocket
      surgery in mice with hindlimb ischemia compared with that in non-ischemic control
      mice. In rabbits with hindlimb ischemia, circulating EPCs were further augmented
      after pretreatment with GM-CSF, with a corresponding improvement in hindlimb
      neovascularization. There was direct evidence that EPCs that contributed to
      enhanced corneal neovascularization were specifically mobilized from the bone
      marrow in response to ischemia and GM-CSF in mice transplanted with bone marrow
      from transgenic donors expressing beta-galactosidase transcriptionally regulated
      by the endothelial cell-specific Tie-2 promoter. These findings indicate that
      circulating EPCs are mobilized endogenously in response to tissue ischemia or
      exogenously by cytokine therapy and thereby augment neovascularization of
      ischemic tissues.

PMID- 10202936
TI  - Stable restoration of the sarcoglycan complex in dystrophic muscle perfused with
      histamine and a recombinant adeno-associated viral vector.
AB  - Limb-girdle muscular dystrophies 2C-F represent a family of autosomal recessive
      diseases caused by defects in sarcoglycan genes. The cardiomyopathic hamster is a
      naturally occurring model for limb-girdle muscular dystrophy caused by a primary
      deficiency in delta-sarcoglycan. We show here that acute sarcolemmal disruption
      occurs in this animal model during forceful muscle contraction. A recombinant
      adeno-associated virus vector encoding human delta-sarcoglycan conferred
      efficient and stable genetic reconstitution in the adult cardiomyopathic hamster
      when injected directly into muscle. A quantitative assay demonstrated that vector
      transduced muscle fibers are stably protected from sarcolemmal disruption; there
      was no associated inflammation or immunologic response to the vector-encoded
      protein. Efficient gene transduction with rescue of the sarcoglycan complex in
      muscle fibers of the distal hindlimb was also obtained after infusion of
      recombinant adeno-associated virus into the femoral artery in conjunction with
      histamine-induced endothelial permeabilization. This study provides a strong
      rationale for the development of gene therapy for limb-girdle muscular dystrophy.

PMID- 10202937
TI  - Fludarabine-induced immunosuppression is associated with inhibition of STAT1
      signaling.
AB  - Fludarabine is a nucleoside analog used in the treatment of hematologic
      malignancies that can induce severe and prolonged immunosuppression. Although it
      can be incorporated into the DNA of dividing cells, fludarabine is also a potent
      inhibitor of cells with a low growth fraction, thus it must have other mechanisms
      of action. STAT1, which is activated in response to many lymphocyte-activating
      cytokines including the interferons, is essential for cell-mediated immunity, as
      the absence of this protein is associated with prominent defects in the ability
      to control viral infections. Here we show that fludarabine, but not the
      immunosuppressant cyclosporine A, inhibits the cytokine-induced activation of
      STAT1 and STAT1-dependent gene transcription in normal resting or activated
      lymphocytes. Fludarabine caused a specific depletion of STAT1 protein (and mRNA)
      but not of other STATs. This loss of STAT1 was also seen in cells from patients
      treated with fludarabine in vivo. Brief exposure to fludarabine led to a
      sustained loss of STAT1, analogous to the prolonged period of immunosuppression
      induced by exposure to the drug in vivo. Thus, STAT1 may be a useful target in
      the development of new immunosuppressive and antineoplastic agents.

PMID- 10202938
TI  - Environmental enrichment inhibits spontaneous apoptosis, prevents seizures and is
      neuroprotective.
AB  - The mammalian brain has a high degree of plasticity, with dentate granule cell
      neurogenesis and glial proliferation stimulated by an enriched environment
      combining both complex inanimate and social stimulation. Moreover, rodents
      exposed to an enriched environment both before and after a cerebral insult show
      improved cognitive performance. One of the most robust associations of
      environmental enrichment is improved learning and memory in the Morris water
      maze, a spatial task that mainly involves the hippocampus. Furthermore, clinical
      evidence showing an association between higher educational attainment and reduced
      risk of Alzheimer and Parkinson-related dementia indicates that a stimulating
      environment has positive effects on cerebral health that may provide some
      resilience to cerebral insults. Here we show that in addition to its effects on
      neurogenesis, an enriched environment reduces spontaneous apoptotic cell death in
      the rat hippocampus by 45%. Moreover, these environmental conditions protect
      against kainate-induced seizures and excitotoxic injury. The enriched environment
      induces expression of glial-derived neurotrophic factor and brain-derived
      neurotrophic factor and increases phosphorylation of the transcription factor
      cyclic-AMP response element binding protein, indicating that the influence of the
      environment on spontaneous apoptosis and cerebral resistance to insults may be
      mediated through transcription factor activation and induction of growth factor
      expression.

PMID- 10202939
TI  - Tau gene mutation in familial progressive subcortical gliosis.
AB  - Familial forms of frontotemporal dementias are associated with mutations in the
      tau gene. A kindred affected by progressive subcortical gliosis (PSG), a rare
      form of presenile dementia, has genetic linkage to chromosome 17q21-22. This
      kindred (PSG-1) is included in the 'frontotemporal dementias and Parkinsonism
      linked to chromosome 17' group along with kindreds affected by apparently
      different forms of atypical dementias. Some of these kindreds have mutations in
      the tau gene. We report here that PSG-1 has a tau mutation at position +16 of the
      intron after exon 10. The mutation destabilizes a predicted stem-loop structure
      and leads to an over-representation of the soluble four-repeat tau isoforms,
      which assemble into wide, twisted, ribbon-like filaments and ultimately result in
      abundant neuronal and glial tau pathology. The mutations associated with PSG and
      other atypical dementias can be subdivided into three groups according to their
      tau gene locations and effects on tau. The existence of tau mutations with
      distinct pathogenetic mechanisms may explain the phenotypic heterogeneity of
      atypical dementias that previously led to their classification into separate
      disease entities.

PMID- 10202940
TI  - Enrichment of epithelial cells for molecular studies.

PMID- 10202941
TI  - Retention of Tc-99m ECD in delayed SPECT of the brain.
AB  - We determined the effect of retention on the changes in regional biodistribution
      of Tc-99m ECD in the brain. A total of 14 cases, 7 normal volunteers and 7
      patients with various diagnoses but with very minimal radiologic findings or none
      were included in the study. SPECT images were taken at 30 min, 1, 2, 3, 4 and 6
      hrs after an intravenous injection. Retention rates were calculated in various
      regions and were corrected according to the time decay of technetium. There was a
      tendency for the retention rate to increase up to three hours of imaging and then
      a decrease was noted in most regions of the brain. In the thalamus, increasing
      retention was noted. In conclusion, Tc-99m ECD retention in the different regions
      of the brain varies with time. These differences should always be considered when
      planning and interpreting SPECT quantitative studies.

PMID- 10202942
TI  - Simple scintigraphic parameters with Tc-99m galactosyl human serum albumin for
      clinical staging of chronic hepatocellular dysfunction.
AB  - Technetium-99m labeled diethylenetriaminepentaacetic acid (DTPA)-galactosyl human
      serum albumin (GSA) has been used for hepatocellular functional evaluation. This
      study proposed new and simple parameters to overcome the limitations of
      conventional parameters, and they were applied to the clinical staging of chronic
      liver dysfunction. The study group consisted of 93 patients including 81 with
      liver dysfunction and 12 control patients. In addition to the two conventional
      parameters, namely, receptor index (LHL15 = liver count divided by the sum of
      liver and heart counts at 15 minutes) and clearance index (HH15 = heart count at
      15 minutes divided by the heart count at 3 minutes), 6 new parameters for Tc-99m
      GSA uptake and clearance were generated. The conventional receptor index of LHL15
      showed a large variation depending on the size of region of interest (ROI) over
      the heart. The LHL15 normalized by the ROI size (nLHL15) showed more stable data
      and a better separation of mild liver dysfunction. A hyperbolic relationship
      between the LHL15 and HH 15 changed to a linear relationship by using the nLHL15
      index. The combination of the liver to heart average count ratio at 15 minutes
      (LH 15) and T-half (minute) of the heart count also could differentiate each
      stage well. In conclusion, the use of the ROI-area normalized nLHL is recommended
      instead of the conventional LHL15. The indices of LH15 and T-half could be
      alternatively used as practical parameters for clinical staging in liver
      function.

PMID- 10202943
TI  - Phase changes caused by hyperventilation stress in spastic angina pectoris
      analyzed by first-pass radionuclide ventriculography.
AB  - To understand the effect of hyperventilation (HV) stress in patients with spastic
      angina, left ventricular (LV) contraction was analyzed by quantitative phase
      analysis. The study was performed on 36 patients with spastic angina pectoris,
      including vasospastic angina pectoris (VspAP: 16 patients) and variant angina
      pectoris (VAP: 20 patients). First-pass radionuclide ventriculography (first-pass
      RNV) was performed at rest and after HV stress, and standard deviation of the LV
      phase distribution (SD) was analyzed. The SD was lower in patients with VspAP
      than in VAP (12.8+/-1.4 degrees vs. 14.6+/-2.2 degrees, p < 0.005) at rest. After
      HV stress, the SD (HVSD) tended to increase in VspAP patients (62.5%), whereas
      the SD decreased in VAP patients (70%). Due to HV stress, the percentage change
      in SD (%SD) in VspAP patients was 8.9+/-23.7% whereas that in VAP patients was 
      9.1+/-17.3% (p < 0.01). Moreover, phase histograms were divided into HVSD
      increase and HVSD decrease groups. The HVSD increase group had a decrease of
      HVEF, but the HVSD decrease group tended to have more decreased HVEF than the
      HVSD increase group. These results indicate that spastic angina pectoris patients
      show various responses to HV stress. The HVSD increase group might have
      additional myocardial ischemia due to regional coronary spasm. In contrast, in
      the HVSD decrease group severe LV dysfunction or diffuse wall motion abnormality
      might have been generated, and this caused a reduction in the SD value. Phase
      analysis would therefore add new information regarding electrocardiographically
      silent myocardial ischemia due to coronary spasm, and HV stress might increase
      sensitivity for the detection of abnormalities in quantitative phase analysis,
      especially in VspAP patients.

PMID- 10202944
TI  - Evaluation of the cardiac autonomic nervous system in spontaneously non-insulin
      dependent diabetic rats by 123I-metaiodobenzylguanidine imaging.
AB  - OBJECTIVE: To evaluate the sensitivity of 123I-labeled metaiodobenzylguanidine
      (123I-MIBG) scintigraphy in detecting diabetic autonomic nervous system
      disorders. MATERIALS AND METHODS: Thirty-one-week-old male Otsuka Long-Evans
      Tokushima Fatty (OLETF) rats, an animal model of spontaneous non-insulin
      dependent diabetes mellitus, were maintained for 8 weeks with or without 30%
      sucrose solution as a drinking water (n = 3 each). Long-Evans Tokushima Otsuka
      (LETO) rats (n = 3), served as controls. Plasma glucose and insulin levels were
      measured, and 123I-MIBG scintigraphy was performed with a gamma camera equipped
      with a pinhole collimator for animals. Plasma and cardiac tissue cathecolamine
      levels were also determined. RESULTS: Plasma glucose levels of OLETF rats with
      and without sucrose loading (554+/-106 and 141+/-1.5 mg/dl respectively) were
      significantly higher than those of LETO rats (116+/-3.7 mg/dl). Norepinephrine
      concentrations in heart and plasma tended to be lower in diabetic rats. The
      washout rate of 123I-MIBG in diabetic rats was significantly higher than the rate
      in control rats. Cardiac uptake of 123I-MIBG, calculated as % dose/g of tissue,
      was significantly lower in diabetic rats than in control rats. CONCLUSION: These
      results suggest that myocardial 123I-MIBG scintigraphy is suitable for assessing
      cardiac sympathetic activity noninvasively in diabetic states, even in the early
      stages.

PMID- 10202945
TI  - Effects of ion channel modulators in the influx and efflux of Tc-99m-MIBI.
AB  - Possible involvement of cell membrane ion transport systems in the uptake and
      extrusion of Tc-99m-MIBI was investigated by using various buffers with or
      without Na+ and Ca++, and ion transport inhibitors in a tumor cell line. The ion
      transport modulators dimethyl amiloride (DMA), verapamil, flunarizine and
      monensin were used. The uptake of Tc-99m-MIBI was significantly increased in all
      buffers containing either Na+ or Ca++ alone or none of them. There was
      significantly increased uptake of Tc-99m-MIBI especially in buffers without Na+.
      Verapamil, a L-type Ca++ channel blocker, increased Tc-99m-MIBI uptake in all
      buffers. Flunarizine, which inhibits Na+/ Ca++ channels, caused significantly
      increased accumulation of Tc-99m-MIBI only in buffer containing both Na+ and
      Ca++. Monensin, a sodium ionophore, significantly increased uptake of Tc-99m
      MIBI. DMA, a potent Na+/H+ antiport inhibitor, significantly inhibited the uptake
      of Tc-99m-MIBI in all buffers. In conclusion, Tc-99m-MIBI behaves like Na+ during
      its uptake and extrusion. Extrusion of Tc-99m-MIBI may involve both verapamil-
      and flunarizine-sensitive pathways.

PMID- 10202946
TI  - Abnormal fatty acid metabolism in patients with coronary vasospasm.
AB  - Although various noninvasive methods have been used to detect vasospasm, none of
      them are sensitive enough for patients with sporadic attacks. Since abnormal
      fatty acid metabolism is observed in ischemic myocardium, 123I-beta-methyl-p
      iodophenyl pentadecanoic acid (BMIPP), a radiolabeled fatty acid analog, has
      recently been proposed as a useful tracer for detecting myocardial damage. The
      aim of this study was to clarify the clinical implications of decreased
      myocardial BMIPP uptake in patients with vasospastic angina. We evaluated 53
      patients with vasospastic angina (32 with clinically documented vasospasm [Group
      A] and 21 with vasospasm induced by ergonovine provocation [Group-B]) and 27
      control subjects, 20 in Group-A were re-evaluated 6 months after medical
      treatment. The territorial regions of vasospasm-induced coronary artery, the wall
      motion by left ventriculography, and BMIPP uptake were compared. Vasospasm was
      induced in multiple coronary arteries in 29 (55%) patients. Reduced wall motion
      and decreased BMIPP uptake were observed in 19 (36%) patients and 47 (89%)
      patients, respectively. The sensitivity and specificity of determination of
      vasospasm-induced coronary arteries with BMIPP scintigraphy were 71% (69/97
      coronary arteries) and 88% (126/143), respectively. Vasospasm was re-induced by
      ergonovine provocation in 8 patients (Group-I) and not re-induced in 12 (Group
      II) after treatment. In Group-I, improvement of decreased BMIPP uptake was lower
      than in Group-II (19+/-11 vs. 59+/-22%, mean+/-SD, p < 0.001). The regions in
      which vasospasm was re-provoked exhibited decreased BMIPP uptake. Abnormal fatty
      acid metabolism was more often observed than wall motion abnormality in the
      vasospastic region in patients with vasospastic angina. BMIPP scintigraphy is a
      highly accurate and non-invasive technique for determining the presence and
      location of vasospasm.

PMID- 10202947
TI  - Reverse redistribution of Tc-99m-tetrofosmin in patients with acute myocardial
      infarction.
AB  - We examined reverse redistribution (RR) of Tc-99m-tetrofosmin after a single
      injection in patients with acute myocardial infarction (AMI). Tc-99m-tetrofosmin
      myocardial SPECT was performed in 28 patients with AMI 10-14 days after the
      onset. Myocardial images were obtained 30 min and 180 min after the injection of
      740 MBq of Tc-99m-tetrofosmin. The left ventricular wall was divided into 9
      segments. Regional myocardial uptakes of Tc-99m-tetrofosmin were scored by 4
      point scoring (0 = normal, 1 = mildly reduced, 2 = moderately reduced, and 3 =
      defect). RR was defined as an increase of more than 1 in the regional score in
      images at 180 min. RR of Tc-99m-tetrofosmin was observed in 17 of 20 patients
      with direct PTCA and 3 of 8 patients without reperfused therapy. RR was observed
      in 61 of all 252 segments. Coronary angiography performed 1 month later revealed
      that the infarct-related artery was patent in 19 of 20 patients (95%) with RR and
      in 3 of 8 patients (37.5%) with persistent defects (PD) (p < 0.05). In segment-by
      segment analysis, the incidence of regional wall motion abnormality I month later
      was reduced in regions with RR compared to those with PD (p < 0.0001). In
      conclusion, RR of Tc-99m-tetrofosmin was frequently observed in patients with
      successful direct PTCA. As the segments with RR showed signs of preserved
      function 1 month later, this phenomenon may reflect a salvaged myocardium in AMI.

PMID- 10202948
TI  - Ga-67 tumor scan in malignant diffuse mesothelioma--comparison with CT and
      pathological findings.
AB  - Malignant diffuse mesothelioma is characterized by more difficult diagnosis and
      worse prognosis than other pleural tumors. In the Department of Thoracic Surgery,
      Hyogo Medical Center for Adults, 11 patients underwent panpleuropneumonectomy for
      this disease between January, 1988 and March, 1993. In 7 of these cases, Ga-67
      scans were obtained before the operation. To clarify the factors affecting Ga-67
      uptake in the pleural tumor, we compared Ga-67 uptake on the involved side of the
      thorax with CT and the pathological findings of the tumor. Regarding the use of
      Ga-67 scan imaging for the diagnosis of this disease, a number of related
      findings must be considered, such as an encircled wide Ga-67 uptake in the
      thickened pleural involvement and a diffuse slight Ga-67 uptake on the affected
      side with very slight involvement of the pleura. When the involved pleural
      thickness was over 6 mm, a definite correlation was found between the degree of
      Ga-67 uptake and the macroscopic thickness of mesothelioma in resected specimens.
      Thickness of the pleura on CT images demonstrates the real tumor thickness in the
      case of thickened involvement but in the case of thin involvement the real
      thickness of active mesothelioma could not be identified. No definite correlation
      was found between the degree of Ga-67 uptake and the histological type, or among
      microscopic findings, such as the extent of tumor parenchyma, interstitial volume
      and tumor vascularity. Our results suggest that the Ga-67 scan is very useful for
      revealing the extent of pleural involvement, especially when this involvement is
      more than 6 mm thick.

PMID- 10202949
TI  - Increased FDG uptake in the wall of the right atrium in people who participated
      in a cancer screening program with whole-body PET.
AB  - The purpose of this study was to evaluate the characteristics of patients who
      showed increased FDG uptake in the wall of the right atrium. We have encountered
      10 patients with increased activity in the wall of the right atrium among a total
      of 2,367 examinees who participated in our cancer screening program with whole
      body PET. The mean age of these examinees was 62.9 yr, higher than that of the
      total population. All suffered from cardiac disorders, especially atrial
      fibrillation. FDG accumulated almost exclusively in the wall of the right atrium,
      whereas only slight activity was seen in the wall of the left atrium. Although
      the average size of the right atria was significantly enlarged, left atria were
      more severely dilated than right ones. Therefore overload does not seem to
      account for the FDG accumulation in the wall of the right atrium. In conclusion,
      the increased activity in the wall of the right atrium was a rare finding that
      was made in older people who suffered from cardiac disease. Although the
      mechanism of induction of the high metabolic state of glucose in the wall of the
      right atrium remains unclear, this unusual activity would be another false
      positive finding in cancer screening with whole-body FDG PET.

PMID- 10202950
TI  - A trial for the quantification of regional myocardial blood flow with continuous
      infusion of Tc-99m MIBI and dynamic SPECT.
AB  - We propose a new method to quantify regional myocardial blood flow (rMBF) by
      continuous infusion of Tc-99m MIBI and dynamic SPECT. METHODS: Five patients with
      old myocardial infarction were studied. During continuous infusion of MIBI
      (approximately 740 MBq) with a syringe pump in 10 min, dynamic SPECT scan was
      performed every minute and lasted 20 min after the start of infusion to identify
      myocardial uptake of MIBI. Input function was obtained from the radioactivity in
      the left ventricle (LV) in dynamic SPECT images. Spillover fraction between LV
      and myocardium (M) was corrected with phantom data. The influx constant (Ku) was
      calculated by Patlak plot graphical analysis, and compared with rMBF measured by
      PET (F) with N-13 ammonia based on Patlak plot analysis with correction for the
      extraction fraction. To correct the limited first-pass extraction of MIBI,
      linearization correction by means of the permeability-surface area (PS) product
      value was also applied. RESULTS: Spillover fractions of MIBI were 0.169+/-0.056
      from LV to M, and 0.042+/-0.021 from M to LV. Ku was well correlated with F (Ku =
      0.057 + 0.220F, r = 0.83, p < 0.01) and the slope and correlation were improved
      after linearizaiton (F(MIBI) = -0.131+0.858F, r = 0.94, p < 0.01). CONCLUSION:
      The proposed method has the potential to be a clinically feasible tool for
      quantitative measurement of rMBF.

PMID- 10202951
TI  - Performance stability of SHR-2000 high resolution PET for animal research.
AB  - The performance of a high resolution positron emission tomography (PET) system
      SHR-2000 for animal studies was re-evaluated six years after its installation.
      The system employs a detector array consisting of BGO crystals that are 1.7 mm
      (transaxially) by 10 mm (axially) by 30 mm (deep). A block detector, which is a
      position-sensitive photomultiplier tube (PMT) coupled to 4 arrays of BGO crystals
      has been adopted to the system. There are 15 block detectors positioned to form a
      35 cm diameter ring with a field of view (FOV) of 17 cm by 4.6 cm axially, giving
      the system a 7 slice imaging capability. For six year workload in spatial
      resolution (FWHM), there were approximately a 2.6% increase at tangential FOV and
      a 7.5% increase at radial FOV. In axial resolution (FWHM) there was almost no
      change. The count rate loss for the true count rate increased 1.3% at 200 kBq/
      ml. The average slice sensitivity showed a decrease of approximately 4.1%, and in
      scatters it showed an increase of approximately 1.4%. In animal experiments, the
      bones of guinea pigs were clearly identified with 18F fluoride ion. These
      experiments show that after a six year workload, the system also maintains good
      performance and has good stability.

PMID- 10202952
TI  - Aggregated human serum immunoglobulin A1 induced by neuraminidase treatment had a
      lower number of O-linked sugar chains on the hinge portion.
AB  - A part of human serum immunoglobulin A1(IgA1) was aggregated by treatment with
      neuraminidase. Aggregated IgA1 was separated from non-aggregated IgA1 by gel
      permeation chromatography. The prepared asialo-hinge glycopeptide (asialo-HGP)
      from both IgA1 subfractions was treated with beta-galactosidase to determine the
      number of beta-linked sugar chains attached on the hinge region. Removal of the
      galactose residue from asialo-HGP resulted in the HPLC separation of three major
      peaks. MALDI-TOFMS analysis of the glycopeptides also indicated the presence of
      three HGP components with three, four and five N-acetylgalactosamine (GalNAc)
      residues, respectively. Comparison of their relative content among the
      glycopeptide components showed a higher content of the HGP component with a lower
      number of GalNAc residues on aggregated IgA1. Thus, asialo-HGP prepared from
      aggregated IgA1 induced by neuraminidase treatment had an incomplete core
      structure of O-linked oligosaccharides. Especially, the result suggested that the
      reduced number of the attached O-linked oligosaccharides on IgA1 take part in
      phenomena such as self-aggregation of asialo-IgA1.

PMID- 10202953
TI  - Immunological screening of drugs of abuse and gas chromatographic-mass
      spectrometric confirmation of opiates and cocaine in hair.
AB  - The work presents an analytical strategy to detect drugs of abuse in hair. It
      involves two sequential steps: a screening by a simple enzyme-linked
      immunosorbent assay (ELISA) methodology to detect opiates, cocaine and its
      metabolites, and benzodiacepines, followed by confirmation of opiates and cocaine
      metabolites in positive samples by gas chromatography coupled to mass
      spectrometry (GC-MS). In the same GC-MS run other drugs for substitution therapy
      (e.g. methadone and its main metabolite) can also be detected. After a double
      washing of hair samples with dichloromethane, hair specimens were cut into small
      pieces and 10 mg samples were incubated in 2 ml of methanol-trifluoroacetic acid
      (9:1) mixture, overnight at 37 degrees C. Aliquots of the extract were then
      evaporated, reconstituted in buffer and analysed according to the ELISA
      procedure. Confirmation involved solid-phase extraction of another fraction of
      the extract kept at -20 degrees C, derivatization with heptafluorobutyric
      anhydride and hexafluoroisopropanol and detection of cocaine, benzoylecgonine,
      ecgonine methylester, cocaethylene, morphine, codeine, 6-monoacetylmorphine,
      methadone and 2-ethylidene-1.5-dimethyl-3,3-diphenylpirrolidine (methadone
      metabolite) by selective ion monitoring after gas chromatographic separation.
      During the development of the method it was verified that no more than 10% of
      cocaine, opiates and benzodiacepines were lost when dichloromethane was used to
      wash real samples. The results also confirmed the increase of extractability
      power of TFA when it was added to methanol: the recovery for the analytes
      (cocaine and its metabolites and opiates) added to methanol-TFA alone was of the
      order of 90% except for benzoylecgonine (75%), and the recovery for the analytes
      added to methanol-TFA extract of drug-free hair was about 90% for all analytes
      except for benzoylecgonine and 6-MAM (around 70%). Regarding the stability of
      labile compounds, only small amounts of ecgonine methylester (2.3%) and morphine
      (7.2%) were produced, from cocaine and 6-MAM respectively, after the whole
      extraction procedure and two weeks of storage of methanol-TFA extracts at -20
      degrees C. Satisfactory results were obtained when the procedures were applied to
      the analysis of external proficiency testing hair samples and actual specimens
      from drug addicts.

PMID- 10202954
TI  - Detection of metabolites of lysergic acid diethylamide (LSD) in human urine
      specimens: 2-oxo-3-hydroxy-LSD, a prevalent metabolite of LSD.
AB  - Seventy-four urine specimens previously found to contain lysergic acid
      diethylamide (LSD) by gas chromatography-mass spectrometry (GC-MS) were analyzed
      by a new procedure for the LSD metabolite 2-oxo-3-hydroxy-LSD (O-H-LSD) using a
      Finnigan LC-MS-MS system. This procedure proved to be less complex, shorter to
      perform and provides cleaner chromatographic characteristics than the method
      currently utilized by the Navy Drug Screening Laboratories for the extraction of
      LSD from urine by GC-MS. All of the specimens used in the study screened positive
      for LSD by radioimmunoassay (Roche Abuscreen). Analysis by GC-MS revealed
      detectable amounts of LSD in all of the specimens. In addition, isolysergic
      diethylamide (iso-LSD), a byproduct of LSD synthesis, was quantitated in 64 of
      the specimens. Utilizing the new LC-MS-MS method, low levels of N-desmethyl-LSD
      (nor-LSD), another identified LSD metabolite, were detected in some of the
      specimens. However, all 74 specimens contained O-H-LSD at significantly higher
      concentrations than LSD, iso-LSD, or nor-LSD alone. The O-H-LSD concentration
      ranged from 732 to 112 831 pg/ml (mean, 16340 pg/ml) by quantification with an
      internal standard. The ratio of O-H-LSD to LSD ranged from 1.1 to 778.1 (mean,
      42.9). The presence of O-H-LSD at substantially higher concentrations than LSD
      suggests that the analysis for O-H-LSD as the target analyte by employing LC-MS
      MS will provide a much longer window of detection for the use of LSD than the
      analysis of the parent compound, LSD.

PMID- 10202955
TI  - Enantioselective high-performance liquid chromatographic method for the
      determination of methadone and its main metabolite in urine using an AGP and a C8
      column coupled serially.
AB  - A simple and sensitive method for the enantioselective high-performance liquid
      chromatographic determination of methadone and its main metabolite, EDDP, in
      human urine is described. (-)-(R)-Methadone, (+)-(S)-methadone, (+)-(R)-EDDP, (-)
      (S)-EDDP and imipramine as an internal standard are detected by ultraviolet
      detection at 200 nm. The enantiomers of methadone and EDDP were extracted from
      human urine by a simple liquid-liquid extraction procedure. The extracted sample
      was reconstructed in mobile phase and the enantiomers of methadone and EDDP were
      quantitatively separated by HPLC on a short analytical LiChrospher RP8 column
      coupled in series with a chiral AGP column. Determination of all four enantiomers
      was possible in the range of 0.03 to 2.5 microM. The recoveries of methadone
      enantiomers and EDDP enantiomers added to human urine were about 90% and 80%,
      respectively. The method was applicable for determination of methadone
      enantiomers and the enantiomers of its main metabolite in urine samples from
      methadone maintenance patients and patients suffering from severe chronic pain.

PMID- 10202956
TI  - Multi-residue analysis of anabolics in calf urine using high-performance liquid
      chromatography with diode-array detection.
AB  - We describe the development of an HPLC method with diode-array detection (DAD)
      for the analysis and identification of 20 substances with anabolic properties,
      that are considered as potential growth promoters, to be used for the analysis of
      extracts of calf urine samples. The substances are separated on an RP-Select B
      column using a mobile phase consisting of a mixture of acetonitrile and water.
      Gradient elution from 43-76% acetonitrile in water with a concave curve was used
      to achieve a good separation of the compounds with an acceptable analysis time.
      For the identification, a retention parameter and the UV spectrum were used. The
      retention parameter was the retention time corrected with a reference mixture.
      The latter reduced the standard deviations to about 25% of their original values.
      The limits of detection of the HPLC system ranged from 0.5-5 ng injected amount
      for the androgens, progestagens, stilbenes and resorcylic acid lactones and to 5
      10 ng injected amount for the oestrogens. After extraction from urine the limits
      of detection were increased by the presence of matrix components, but they were
      between 5 and 10 ng injected amount for most of the substances.

PMID- 10202957
TI  - Optimization of separation of a complex mixture of natural and synthetic
      corticoids by micellar liquid chromatography using sodium dodecyl sulphate.
      Application to urine samples.
AB  - A systematic optimization of the separation of a mixture of corticoids by
      micellar liquid chromatography, using sodium dodecyl sulphate as surfactant, a
      Hypersil (250 mm x 3.2 mm I.D.) C18 column, a flow-rate of 0.5 ml min(-1), and UV
      absorbance detection at 245 nm has been carried out. Several mobile phases
      consisting of sodium dodecyl sulphate and different organic modifiers were tested
      of which tetrahydrofuran, PrOH and BuOH were finally selected. On the basis of
      analysis time, resolution and number of compounds separated, a mobile phase
      containing 36 mM sodium dodecyl sulphate and 1.91% butanol allowed the separation
      of thirteen corticoids out of sixteen in about 27 min. Under these conditions the
      optimal concentration of sodium dodecyl sulphate was found to be 36 mM. A
      bivariant optimization method for the mobile phase BuOH-sodium dodecyl sulphate
      corrobored these results. The effects of temperature, ionic strength and flow
      rate effect have also been studied. The most important analytical figures of
      merit were assessed and compared with those obtained using conventional mobile
      phases. The optimized method was applied to human urine samples of subjects
      administered with Dezacor (tablets containing 30 mg of the active ingredient
      deflazacort) with and without sample preparation.

PMID- 10202958
TI  - Liquid chromatographic studies with immobilized neuronal nicotinic acetylcholine
      receptor stationary phases: effects of receptor subtypes, pH and ionic strength
      on drug-receptor interactions.
AB  - Nicotinic acetylcholine receptor (nAChR) alpha3-subunits, beta4-subunits,
      alpha3/beta4-subunit combination and alpha4/beta2-subunit combination were
      immobilized on chromatographic stationary phases and the binding affinities of
      the different nAChR subtypes were chromatographically evaluated. The observed
      relative binding affinities of epibatidine were alpha4/beta2>alpha3/beta4 and
      epibatidine did not bind at alpha3-subunits and beta4-subunits. No significant
      difference in binding affinities was observed on the alpha4/beta2 nAChRs
      immobilized in immobilized artificial membrane (IAM) particles and those
      sterically immobilized on Superdex 200 beads. The effects of mobile phase pH and
      ionic strength on the binding affinities of the alpha3/beta4 nAChRs support were
      also investigated. The results are consistent with the proposed ligand-nAChR
      binding model in which a cationic center exists at the binding site.

PMID- 10202959
TI  - Sensitive semi-microcolumn high-performance liquid chromatographic method for the
      determination of DU-6681, the active parent drug of a new oral carbapenem
      antibiotic, DZ-2640, in human plasma and urine using a column-switching system as
      sample clean-up procedure.
AB  - DZ-2640 is a new oral carbapenem antibiotic having a dihydro-pyrroloimidazole
      ring as a side chain and a pivaloyloxymethyl (POM) ester prodrug of DU-6681, the
      active parent compound. A simple and sensitive column-switching semi-microcolumn
      high-performance liquid chromatographic method for the determination of DU-6681
      in human plasma and urine has been developed. Human plasma was diluted with an
      equal volume of 1 M MOPS buffer (pH 7.0) and the mixture was filtered through an
      Ultrafree C3GV. The resulting filtrate was injected without further cleanup onto
      the HPLC system. Human urine was diluted with an equal volume of 1 M MOPS buffer
      (pH 7.0) and the mixture was directly injected onto the HPLC system. The analyte
      was detected by monitoring the column effluent with UV light at a wavelength of
      300 nm, which resulted in the limit of quantitation of 0.008 microg/ml of plasma
      and 0.32 microg/ml of urine. Calibration curves were linear in the range of 0.008
      to 5.85 microg/ml in plasma and 0.32 to 104.4 microg/ml in urine. The present
      methods showed greatly increased sensitivity for DU-6681 compared to conventional
      HPLC methods and also showed satisfactory recovery, selectivity, precision, and
      accuracy. Stability studies showed that 1 M MOPS buffer (pH 7.0) acted as a
      stabilizer. In plasma and urine diluted with equal volume of the buffer, DU-6681
      showed good stability at -80 degrees C for up to 4 weeks with no significant loss
      of the drug.

PMID- 10202960
TI  - Simultaneous determination of tramadol and its major active metabolite O
      demethyltramadol by high-performance liquid chromatography with electrochemical
      detection.
AB  - A novel, highly sensitive method was developed for simultaneous determination of
      tramadol and its main active metabolite O-demethyltramadol (ODMT) in rat plasma.
      The method involves a single-step extraction procedure and a specific
      determination by high-performance liquid chromatography with electrochemical
      detection, using an ethoxy analogue of tramadol (L-233) as internal standard. The
      dual-electrode detector was operated in the oxidation-screening mode. Absolute
      recoveries of tramadol and ODMT were about 80%. Calibration curves were linear
      over a concentration range of 10-1000 ng/ml for ODMT and 10-10000 ng/ml for
      tramadol with intra- and inter-day coefficients of variation not exceeding 10%
      and 15%, respectively. The limit of quantification for tramadol and ODMT was
      lower than 15 ng/ml and 10 ng/ml using 100 microl of plasma, respectively. The
      described method allows an adequate characterization of the plasma vs. time
      profiles for both compounds.

PMID- 10202961
TI  - Characterisation of the binding of digitoxin and acetyldigitoxin to human serum
      albumin by high-performance affinity chromatography.
AB  - Zonal elution and high-performance affinity chromatography were used to examine
      interactions of the drugs digitoxin and acetyldigitoxin with the protein human
      serum albumin (HSA). This was done by injecting small amounts of digitoxin and
      acetyldigitoxin onto an immobilized HSA column in the presence of mobile phases
      that contained various concentrations of digitoxin, acetyldigitoxin or other
      solutes as competing agents. A fixed concentration of beta-cyclodextrin was also
      present in the mobile phase as a solubilising agent. It was found that digitoxin
      and acetyldigitoxin each had strong interactions at a single common binding site
      on HSA, but with slightly different equilibrium constants for this region.
      Neither compound showed any competition with warfarin or L-tryptophan, which were
      used as probes for binding at the warfarin-azapropazone and indole-benzodiazepine
      sites of HSA. These results confirmed the presence of a separate binding region
      on HSA for digitoxin-related compounds.

PMID- 10202962
TI  - Chiral high-performance liquid chromatographic analysis of enantiomers of
      losigamone, a new candidate antiepileptic drug.
AB  - An assay based on a single-step liquid-liquid extraction from human plasma
      followed by high-performance liquid chromatography on a chiral column was
      developed for the measurement of enantiomers of a racemic new candidate
      antiepileptic drug. Excellent intra- and inter-assay accuracy and precision and
      recovery were demonstrated in the desired concentration range of 0.031 to 5.00
      microg/ml. The method is free from interferences by other anticonvulsant drugs
      and their metabolites. The method is being used in a clinical trial of
      losigamone.

PMID- 10202963
TI  - Solid-phase extraction and high-performance liquid chromatographic determination
      of articainic and its metabolite articainic acid in human serum.
AB  - A new method is described using solid-phase extraction (SPE) for preconcentration
      of articaine and the metabolite articainic acid and high-performance liquid
      chromatography (HPLC) for the determination of both compounds in human serum.
      Articaine and articainic acid were extracted in one step with SDB-RPS disk
      cartridges after precipitation of the serum proteins by perchloric acid. The HPLC
      separation was then performed on a reversed-phase C8 column using phosphate
      buffer-acetonitrile (88:12, v/v). UV absorption at 274 nm was used for measuring
      the analytes with a low limit of quantitation of about 10 ng/ml, which is
      appropriate for pharmacokinetic studies of low dose submucosal injections of the
      local anaesthetic agent articaine hydrochloride in dentistry.

PMID- 10202964
TI  - High-performance liquid chromatographic method for the determination of
      atracurium and laudanosine in human plasma. Application to pharmacokinetics.
AB  - A high-performance liquid chromatographic method coupled with fluorimetric
      detection has been developed for the determination of atracurium and its major
      metabolite, laudanosine, in human plasma. The detection is performed at 240 nm
      for excitation and 320 nm for emission. Verapamil was used as the internal
      standard. The proposed technique, involving the direct precipitation of plasma
      proteins is reproducible, selective and sensitive. Linear detector responses were
      observed for the calibration curve standards in the range of 40 to 2000 ng/ml.
      Precision, expressed as C.V., was in the range 1 to 14%. The limit of
      quantification for both atracurium and laudanosine was 40 ng/ml. The method has
      been validated and stability tests under various conditions have been performed.
      This method has been used to determine the pharmacokinetic profile of atracurium
      and laudanosine in patients with acute respiratory distress syndrome.

PMID- 10202965
TI  - Determination of phosphonoformate (foscarnet) in calf and human serum by
      automated solid-phase extraction and high-performance liquid chromatography with
      amperometric detection.
AB  - An isocratic high-performance liquid chromatographic method with automated solid
      phase extraction has been developed to determine foscarnet in calf and human
      serums. Extraction was performed with an anion exchanger, SAX, from which the
      analyte was eluted with a 50 mM potassium pyrophosphate buffer, pH 8.4. The
      mobile phase consisted of methanol-40 mM disodium hydrogenphosphate, pH 7.6
      containing 0.25 mM tetrahexylammonium hydrogensulphate (25:75, v/v). The analyte
      was separated on a polyether ether ketone (PEEK) column 150x4.6 mm I.D. packed
      with Kromasil 100 C18, 5 microm. Amperometric detection allowed a quantification
      limit of 15 microM. The assay was linear from 15 to 240 microM. The recovery of
      foscarnet from calf serum ranged from 60.65+/-1.89% for 15 microM to 67.45+/
      1.24% for 200 microM. The coefficient of variation was < or = 3.73% for intra
      assay precision and < or =7.24% for inter-assay precision for calf serum
      concentrations ranged from 15 to 800 microM. For the same samples, the deviation
      from the nominal value ranged from -8.97% to +5.40% for same day accuracy and
      from -4.50% to +2.77% for day-to-day accuracy. Selectivity was satisfactory
      towards potential co-medications. Replacement of human serum by calf serum for
      calibration standards and quality control samples was validated. Automation
      brought more protection against biohazards and increase in productivity for
      routine monitoring and pharmacokinetic studies.

PMID- 10202966
TI  - Automated multi-residue isolation of fluoroquinolone antimicrobials from
      fortified and incurred chicken liver using on-line microdialysis and high
      performance liquid chromatography with programmable fluorescence detection.
AB  - Isolation of the quinolones, sarafloxacin (SAR), oxolinic acid (OXA), and
      flumequine (FMQ), from fortified chicken liver tissues, and SAR incurred chicken
      liver tissues was achieved by combined liquid-liquid extraction and aqueous on
      line microdialysis using the automated trace enrichment of dialysates (ASTED)
      system. Analysis of tissue isolates after ASTED clean-up was performed using
      reversed-phase HPLC and programmable fluorescence detection. Overall recoveries
      of SAR, OXA and FMQ from samples fortified over a concentrations range of 1-100
      ppb were 94, 97 and 87% with overall inter-assay variability of 4.2, 4.1 and
      3.6%, respectively. Chicken liver samples incurred with SAR at three
      concentration levels also were tested by the ASTED method. The method exhibited
      high peak resolution (3.4-4.2 on average), a high signal-to-noise ratio, and
      demonstrated good precision. The ASTED-HPLC method overall had a lower limit of
      detection (LOD) of 0.2 ppb, and a limit of quantitation (LOQ) of 1 ppb.

PMID- 10202967
TI  - Determination of antifilarial compound UMF-078 and its metabolites in plasma by
      high-performance liquid chromatography.
AB  - UMF-078, methyl (+/-)-[5-(alpha-amino-4-fluorobenzyl)benzimidazol-2-yl]carba
      mate, is a new antifilarial compound being developed by the World Health
      Organization. In the present study, a HPLC method for the simultaneous estimation
      of UMF-078 and its metabolites (flubendazole, decarbamoylated flubendazole,
      UMF060 and decarbamoylated UMF-060) in plasma was developed, validated and
      applied to pharmacokinetic studies. Linearity was observed between 20 and 1000
      ng/ml for decarbamoylated UMF-060 and between 10 and 500 ng/ml for other
      analytes. Recoveries were consistent over the concentration ranges studied for
      all the analytes. Variations in intra- and inter-batch accuracy and precision
      were within acceptable limits of +/-20% at the lowest limit of quantitation,
      whereas at higher concentrations it was +/-15%. The analytes showed stability up
      to two freeze-thaw cycles in plasma. No degradation was observed for any of the
      analytes even after 72 h of storing the dry plasma extracts at -30 degrees C. The
      assay method was employed to study the pharmacokinetics of hydrochloride salt of
      UMF-078 in rats. The parent compound and its metabolites viz: decarbamoylated UMF
      060, UMF-060 and flubendazole were quantitated in serum and the compounds could
      be monitored up to 168 h post-dose.

PMID- 10202968
TI  - Quantitative high-performance liquid chromatography-based detection method for
      calphostin C, a naturally occurring perylenequinone with potent antileukemic
      activity.
AB  - Calphostin C is a potent inhibitor of protein kinase C and can induce Ca2+
      dependent apoptosis in human ALL cells. Further development of calphostin C will
      require detailed pharmacodynamic studies in preclinical animal models. Therefore,
      we established a sensitive and accurate high-performance liquid chromatography
      (HPLC)-based quantitative detection method for the measurement of calphostin C
      levels in plasma. Extraction of calphostin C from plasma was performed by
      precipitation of plasma protein using acetonitrile and an aliquot of extracted
      supernatant was injected onto a Hewlett-Packard HPLC system constituting a 250x4
      mm LiChrospher 100, RP-18 (5 microm) in conjunction with a 4x4 mm LiChrospher
      100, RP-18 guard column (5 microm). The eluted compounds were detected by diode
      array detection set at a wavelength of 479 nm. Acetonitrile-water containing 0.1%
      trifluoroacetic acid and 0.1% triethylamine (70:30, v/v) was used as the mobile
      phase. The average extraction recovery from plasma was 97.3%. Good linearity
      (r>0.999) was observed throughout the concentration range of 0.05-40 microM for
      calphostin C in 50 microl of plasma. Intra- and inter-assay variabilities were
      less than 6% in plasma. The lowest detection limit of calphostin C in 50 microl
      plasma was 0.02 microM at a signal-to-noise ratio of approximately 3. The
      availability of this assay will now permit detailed pharmacodynamic and
      pharmacokinetic studies of calphostin C in vivo.

PMID- 10202969
TI  - Quantitative analysis of Z-2-[4-(4-chloro-1,2-diphenyl-but-1-enyl)phenoxy]ethanol
      in human plasma using high-performance liquid chromatography.
AB  - A highly sensitive and precise high-performance liquid chromatography (HPLC)
      assay was developed and validated for the quantitation of Z-2-[4-(4-chloro-1,2
      diphenyl-but-1-enyl) phenoxy]ethanol (FC-1271a) in human plasma. Plasma samples
      (1.0 ml) containing FC-1271a and internal standard (toremifene citrate;
      Farestono) were extracted using a 2% 1-butanol, 98% hexane solution with an
      extraction efficiency of >97%. Samples were reconstituted in methanol, irradiated
      with high intensity ultraviolet light (254 nm) for 1 min, and injected onto a C18
      reverse phase column. Samples were eluted isocratically at a flow-rate of 0.5
      ml/min with a mobile phase consisting of 6.5% water and 0.5% triethylamine in
      methanol. The fluorescence of photochemically activated compounds was detected
      using a fluorometer set at an excitation wavelength of 266 nm and emission
      wavelength of 370 nm. Under these assay conditions, standard calibration curves
      were linear through a concentration range of 10-400 ng/ml. In summary, we have
      developed and validated an HPLC assay to quantitate FC-1271a in human plasma.

PMID- 10202970
TI  - Simultaneous determination of NK-104 and its lactone in biological samples by
      column-switching high-performance liquid chromatography with ultraviolet
      detection.
AB  - A simple and sensitive column-switching HPLC method has been developed for the
      simultaneous determination of NK-104 (HMG-CoA reductase inhibitor) and its
      lactone in human and dog plasma. Plasma sample was extracted with methyl tert
      butyl ether and then the extract was subjected to methylation with diazomethane
      to prevent the mutual conversion between NK-104 and its lactone. The extract was
      injected into the column-switching HPLC system. The calibration curves of NK-104
      and NK-104 lactone were linear over the ranges 0.5 to 100 ng/ml for human plasma
      samples and 0.5 to 500 ng/ml for dog plasma, respectively. The intra-day and
      inter-day C.V. values of these analytes were less than 13.3%. The intra-day and
      inter-day accuracies of these analytes were between -14.0 and 6.5%. The proposed
      method has been applied to plasma samples obtained after oral administration of a
      single 2 mg dose of NK-104 to volunteers.

PMID- 10202971
TI  - Gas chromatographic-mass spectrometric analysis of hydroxylamine for monitoring
      the metabolic hydrolysis of metalloprotease inhibitors in rat and human liver
      microsomes.
AB  - A gas chromatographic-mass spectrometric (GC-MS) method was developed for the
      analysis of hydroxylamine (HA) in supernatants obtained from liver microsomes. HA
      monitoring was used to determine the metabolic hydrolysis of two hydroxamic acid
      based matrix metalloprotease inhibitors in rat and human liver microsomes. The
      hydrolysis of the hydroxamic acids to their corresponding carboxylic acids
      releases HA as a common metabolic product. HA was derivatized to acetone oxime by
      addition of acetone to the liver microsomal supernatant, followed by direct
      injection of the supernatant into the GC-MS, with detection of the oxime by
      selected-ion-monitoring. The method is simple, reproducible, and sensitive for
      the determination of the hydrolysis of hydroxamic acid compounds, where
      hydrolysis is the major metabolic pathway. The methodology can be used for rank
      ordering and selecting hydroxamic acid analogs based on their susceptibility to
      hydrolysis.

PMID- 10202972
TI  - High-performance liquid chromatography with peroxyoxalate chemiluminescence
      determination of propentofylline concentrations in rat brain microdialysate.
AB  - A high-performance liquid chromatographic determination of a neuronal cell
      protective compound, propentofylline [3-methyl-1-(5-oxohexyl)-7-propyl-7H-purine
      2(3H),6(1H)-dione] was performed combining a microdialysis technique with
      peroxyoxalate chemiluminescence (PO-CL) detection. The microdialysate was
      subjected to a fluorescent derivatization of propentofylline with 4-(N,N
      dimethylaminosulfonyl)-7-hydrazino-2,1,3-benzoxadiazole (DBD-H) without further
      cleanup, because the membrane used in the microdialysis excluded high-molecular
      mass proteins. The proposed method showed a good linearity in the determination
      range of 0.031 to 1.25 ng/injection; y (microV)=4234 x (ng)- 13.43, r=0.9993
      (y=peak height and x=amount of propentofylline). The very low determination limit
      of 0.031 ng/injection was ca. 200 times more sensitive than that of HPLC-UV
      determination. The HPLC-PO-CL method was applied for the first time to determine
      propentofylline concentration in the dialysate obtained from the rat hippocampus
      after a single oral administration (25 mg/kg). Propentofylline showed its maximum
      extracellular fluid (ECF) concentration of 125.1+/-15.1 ng/ml (mean+/-SD, n=3) at
      0.33 h after administration.

PMID- 10202973
TI  - Determination of hypericin in plasma by high-performance liquid chromatography.
AB  - Hypericin, a polycyclic dianthroquinone, is one of the characteristic ingredients
      of Hypericum perforatum extracts (St. John's wort, HP), which has antidepressant
      effects. Hypericin and the internal standard (I.S.), dansylamide, were extracted
      from plasma utilizing solid-phase extraction (SPE). Chromatography was performed
      using isocratic reversed-phase high-performance liquid chromatography (HPLC) with
      fluorescence end-point detection. The calibration curve was linear over the range
      5-100 ng per ml of plasma. The sensitivity for hypericin was 75 pg on column.
      Mean inter- and intra-assay coefficients of variation (C.V.s) over the range of
      the standard curve were less than 10%. The absolute recovery for hypericin
      averaged 72.6%.

PMID- 10202974
TI  - High-performance liquid chromatographic analysis of nitrite and nitrate in human
      plasma as S-nitroso-N-acetylcysteine with ultraviolet absorbance detection.
AB  - A rapid HPLC method with UV absorbance detection at 333 nm for the measurement of
      nitrite and nitrate in ultrafiltrate samples of human plasma is described. The
      method is based on hydrochloric acid-catalyzed conversion of nitrite by N-acetyl
      L-cysteine to S-nitroso-N-acetyl-L-cysteine and isocratic elution using 10 mM
      NaH2PO4 in acetonitrile-water, pH 2.0 (15:85, v/v). The limit of detection of the
      method is 50 nM nitrite. The method was validated by gas chromatography-mass
      spectrometry.

PMID- 10202975
TI  - Gender differences in cerebral perfusion.

PMID- 10202976
TI  - Dexanabinol; a novel neuroprotective drug in experimental focal cerebral
      ischemia.
AB  - The permanent middle cerebral artery occlusion (PMCAO) model was used to
      investigate the cerebroprotective effects of the synthetic cannabinoid,
      dexanabinol (HU-211). Dexanabinol is a noncompetitive N-methyl-D-aspartate
      antagonist, with antioxidant and anti-TNFalpha properties. Twenty hypertensive
      rats were subjected to PMCAO. Eight were given 4 mg/kg dexanabinol, i.v., 1 h
      after PMCAO, eight received vehicle and four were not injected Five rats
      underwent sham surgery. Infarct volumes were assessed, as well as TNFalpha
      concentrations and NOS activity in brain homogenates. Dexanabinol significantly
      decreased infarct volumes. It also significantly lowered TNFalpha levels in the
      ipsilateral hemisphere although not to the level of sham operated rats. No effect
      could be demonstrated on NOS activity. In conclusion, dexanabinol may be a
      pluripotent cerebroprotective agent.

PMID- 10202977
TI  - DMSO induction of the leukotriene LTC4 by Lewis rat Schwann cells.
AB  - Schwann cells are capable of producing many immunomodulatory molecules, which
      indicates that they may play an active role in autoimmune diseases of the
      peripheral nervous system. We have previously reported production of the
      prostanoids prostaglandin E2 and thromboxane A2, products of arachidonic acid
      metabolism, by Schwann cells. This study reports that Schwann cells are capable
      of producing leukotriene C4, also a product of arachidonic acid metabolism.
      Production of leukotriene C4 was in response to pre-incubation of the Schwann
      cells with the cytokines interferon-gamma and tumour necrosis factor-alpha
      followed by incubation with dimethylsulfoxide. The cytokines alone did not elicit
      a response nor did stimulation with calcium ionophore, phorbol ester or
      lipopolysaccharide.

PMID- 10202978
TI  - Gender-related effects of indomethacin on cerebrovascular CO2 reactivity.
AB  - Prostaglandins are believed to play an important role in the regulation of
      resting cerebral blood flow and in the vasodilatory response to hypercapnia.
      Recently, we reported an increased CO2 reactivity (CR) in premenopausal women
      and, in the past, evidence has accumulated that estrogens might increase basal
      levels of prostaglandin secretion from endothelial cells. Therefore, one may
      speculate that gender differences in CR are possibly mediated by higher
      prostaglandin levels in women. Using transcranial Doppler sonography, we assessed
      CR before and 90 min after a single dose of 100 mg of indomethacin in 22 healthy
      volunteers (11 men, 11 women). Before intake of indomethacin, women had a
      significantly higher CR (4.53+/-0.49 vs. 3.61+/-0.74, P<0.01). Ninety minutes
      after indomethacin administration, CR decreased to 1.53+/-0.93 in women and
      1.60+/-0.92 in men, respectively. The change of CR was 3.00+/-1.29 in women vs.
      2.01+/-1.06 in men (P=0.07). For the entire study population, the decrease of CR
      was linearly correlated with the initial value of CR (rs=0.74, P<0.001). This
      gender-related difference possibly relates to higher prostaglandin levels as
      mediators of an increased CR in premenopausal women, although the exact features
      remain to be clarified.

PMID- 10202979
TI  - Neuritic sprouting with aberrant expression of the nitric oxide synthase III gene
      in neurodegenerative diseases.
AB  - Neuronal loss, synaptic disconnection and neuritic sprouting correlate with
      dementia in Alzheimer's disease (AD). Nitric oxide (NO) is an important synaptic
      plasticity molecule generated by nitric oxide synthase (NOS) oxidation of a
      guanidino nitrogen of L-arginine. Experimentally, the NOS III gene is modulated
      with neuritic sprouting. In a previous study, NOS III expression was found to be
      abnormal in cortical neurons, white matter glial cells, and dystrophic neurites
      in AD and Down syndrome brains. The present study demonstrates the same
      abnormalities in neuronal and glial NOS III expression with massive proliferation
      of NOS III-immunoreactive neurites and glial cell processes in other
      neurodegenerative diseases including: diffuse Lewy body disease, Pick's disease,
      progressive supranuclear palsy, amyotrophic lateral sclerosis, multiple system
      atrophy, and Parkinson's disease. However, each disease, including AD, was
      distinguished by the selective alterations in NOS III expression and sprouting in
      structures marred by neurodegeneration. Double label immunohistochemical staining
      studies demonstrated nitrotyrosine and NOS III co-localized in only rare neurons
      and neuritic sprouts, suggesting that peroxynitrite formation and nitration of
      growth cone proteins may not be important consequences of NOS III enzyme
      accumulation. The results suggest that aberrant NOS III expression and NOS III
      associated neuritic sprouting in the CNS are major abnormalities common to
      several important neurodegenerative diseases.

PMID- 10202981
TI  - Positive symptoms in multiple sclerosis: their treatment with sodium channel
      blockers, lidocaine and mexiletine.
AB  - Patients with multiple sclerosis (MS) often show positive symptoms of painful
      tonic seizure and dysesthesia as well as negative symptoms of paralysis and
      hypesthesia. Positive manifestation is paroxysmal and/or persistent. These are
      considered to be mediated by ectopic impulses generated at the site of
      demyelination, whereas negative symptoms are caused by conduction block.
      Conduction block at a demyelinated segment should reduce positive symptoms, but
      worsen negative ones. As reported previously, lidocaine, an Na channel blocker
      unmasks silent negative symptoms presumably by further reducing the action
      current in demyelinated portions and blocking conduction. Furthermore, because it
      blocks Na channels in a voltage- and frequency dependent manner, fibers that
      mediate positive symptoms are preferentially blocked. We administered lidocaine
      to 30 MS patients with positive symptoms. Lidocaine (mean plasma level, 2.4
      pg/ml) almost completely abolished the paroxysmal manifestation of painful tonic
      seizures, neuralgic attacks, paroxysmal itching, and Lhermitte's sign. It also
      markedly alleviated persistent symptoms, but less so than paroxysmal symptoms.
      Similar effects were obtained with orally-administered mexiletine (300-400
      mg/day), a derivative of lidocaine, but to a lesser extent. Na channel blockers
      have a dual effect on symptoms in MS, depending on whether symptoms are positive
      or negative. The mechanism that produces positive symptoms and the effects of the
      drugs on these symptoms are discussed.

PMID- 10202980
TI  - Sematic memory deficit in multiple sclerosis; impaired understanding of
      conceptual meanings.
AB  - The aim of the present study was to determine whether a cognitive decline,
      related to multiple sclerosis (MS), also involves deficits in semantic memory.
      Semantic memory function was evaluated by studying the conscious understanding of
      conceptual meanings. A group of MS patients with cognitive decline was presented
      with four tasks concerning concepts, their attributes and relationships to other
      concepts. The tasks were designed to measure spontaneous, cued and recognition
      performance separately. The patients had difficulties in understanding conceptual
      meanings. Easing the retrieval demands of the tasks did not help them to improve
      their performance which was poorer than the control group's on every task used.
      The results indicate a retrieval deficit combined with an underlying storage
      deficit in the semantic memory of MS patients with cognitive decline.

PMID- 10202982
TI  - Increased expression of glial cell line-derived neurotrophic factor mRNA in
      muscle biopsies from patients with amyotrophic lateral sclerosis.
AB  - The expression of glial cell line-derived neurotrophic factor (GDNF) mRNA and
      brain-derived neurotrophic factor (BDNF) mRNA were studied in muscle biopsies
      from five patients with amyotrophic lateral sclerosis (ALS), six patients with
      other neuromuscular diseases and eight healthy control persons. All five patients
      with ALS had higher GDNF mRNA expressions in their biopsies than the healthy
      control group (almost a three fold increase). Among the other patients only one,
      who had a rapidly progressing toxic polyneuropathy, showed a GDNF mRNA expression
      above those of the controls. The BDNF mRNA expressions in the biopsies from the
      ALS patients were in the same range as those from the healthy controls, although
      the mean value of the ALS patients was higher. The only biopsy that showed a
      markedly higher BDNF mRNA expression was taken from one patient with progressive
      muscular atrophy. These results suggest that increased GDNF mRNA expression in
      muscle is an unspecific response to ongoing denervation and that this response is
      maintained in ALS, at least temporarily. If increased GDNF mRNA in muscle proves
      to be a constant finding in ALS the rationale for the use of GDNF as a
      therapeutic agent in ALS must be questioned.

PMID- 10202983
TI  - Sporadic amyotrophic lateral sclerosis of long duration mimicking spinal
      progressive muscular atrophy: a clinicopathological study.
AB  - We report an autopsy case of amyotrophic lateral sclerosis (ALS) clinically
      diagnosed as spinal progressive muscular atrophy (SPMA). The patient was a
      Japanese woman without hereditary burden. She developed muscle weakness of the
      distal part of the left lower extremity at age 42, followed by muscle weakness
      and atrophy of the right lower extremity and upper extremities. At age 57, she
      needed transient ventilatory support. Slight weakness in the facial muscles and
      fasciculation of the tongue appeared at age 60. At age 61, she died of sudden
      respiratory arrest. During the clinical course, neurological examination revealed
      neither Babinski signs nor hyperreflexia. The neuropathological examination
      revealed not only neuronal loss with gliosis in the facial nucleus, hypoglossal
      nucleus, and anterior horns of the spinal cord, but also loss of Betz cells and
      degeneration of the pyramidal tracts. Based on these clinicopathological findings
      and review of literature, we conclude that sporadic ALS mimicking SPMA is
      present.

PMID- 10202985
TI  - Cytokine-induced inflammation and long-term stroke functional outcome.
AB  - Inflammatory reactions are involved in the pathogenesis of cerebral ischemia.
      Cytokines exacerbate brain ischemic injury by several mechanisms and they
      activate the synthesis of acute-phase reactants. We evaluated the association
      between cytokine-induced inflammation and functional outcome in 41 patients with
      acute ischemic stroke. Blood samples for interleukin-1 receptor antagonist (IL
      1ra), erythrocyte sedimentation rate (ESR), c-reactive protein (CRP) and
      polymorphonuclear leukocyte (PMNL) count were taken within 48 h from stroke
      onset. Functional outcome was assessed at six months with the Modified Rankin
      Scale. Patients with a Rankin score > or = 3 were classified as dependent
      outcome. The effect of inflammatory variables on outcome was analyzed by logistic
      regression. Mathew score <75 on admission, atrial fibrillation, non-lacunar
      infarct size, ESR>13 mm/h in men or >20 mm/h in women, PMNL count >8 x 10(9)/l,
      CRP>0.8 mg/dl and IL-1ra>500 pg/ml were associated with dependent outcome. On
      multiple logistic regression, severe stroke on admission, non-lacunar infarct
      size and ESR remain in the predictive model of outcome with a sensitivity and
      specificity of 76 and 80%, respectively. This study suggests that in addition to
      clinical evaluation and neuroimaging, measurement of ESR may be useful for the
      early detection of stroke patients with poor long-term functional outcome.

PMID- 10202984
TI  - Improvement in Parkinsonian symptoms after repetitive transcranial magnetic
      stimulation.
AB  - Transcranial magnetic stimulation has been used in the diagnosis of neurological
      lesions, but has also been shown to be useful in the treatment of depression. We
      have now examined the effect of applying transcranial magnetic stimulation daily
      for 10 days in a sample of 10 patients with Parkinson's disease in whom maximal
      benefit was being obtained from drug therapy. The subjects were followed for six
      months and showed significant improvements over this period when assessed using a
      range of measures. It is suggested that transcranial magnetic stimulation may be
      a valuable technique in the treatment or adjunct treatment of Parkinsonism,
      possibly by inducing changes in brain monoamine levels.

PMID- 10202986
TI  - Focal sensory nerve abnormalities in patients with amyotrophic lateral sclerosis.
AB  - Slowing of sensory nerve conduction is an unexplained finding in patients with
      sporadic amyotrophic lateral sclerosis (ALS). To study the frequency of these
      abnormalities and to study if a predisposition to the development of entrapment
      neuropathies is causal, 23 patients with definite ALS and 23 age-matched healthy
      volunteers were investigated prospectively. Antidromic sensory and motor nerve
      conduction velocities (NCVs) were measured in ulnar and median nerves. Median
      sensory NCV was abnormally low in three patients if compared with the lower limit
      of the control group; and median sensory NCV was abnormally low in nine patients
      (six right, eight left hands) if compared with ipsilateral ulnar sensory NCV.
      Sensory nerve conduction data did not correlate with clinical findings, such as
      forearm weakness or usage of canes. Motor nerve conduction data did not correlate
      with sensory nerve conduction data, with the exception of distal motor latency of
      right median nerves, which correlated with right median sensory NCV. Our findings
      show how affection of sensory fibers of distal segments of median nerves can be
      detected in individual patients with ALS. Nerve entrapment may contribute to this
      affection, but it is not the only cause. This should be considered in discussions
      about diagnostic criteria for ALS.

PMID- 10202987
TI  - Comparison of clinical and demographic features between affected pairs of Italian
      multiple sclerosis multiplex families; relation to tumour necrosis factor genomic
      polymorphisms.
AB  - We conducted a comparative analysis of clinical and demographic findings between
      pairs of relatives (36 sibling and 9 parent/child), concordant for Multiple
      Sclerosis (MS), from 40 MS Italian Multiplex families. A genetic TNF (alpha and
      beta) loci typing in 51 affected and 69 healthy relatives belonging to 25 of
      these families was also performed. The sib pairs resulted significantly
      concordant for age at onset (r=0.414, P<0.013), Progression Index (r=0.34,
      P<0.05) and sensory symptoms at onset (k=0.37), and significantly not concordant
      for sex (k=-0.37), whereas no concordance was found for year at onset and disease
      course. The only significant result in the small group of parent/child pairs was
      that parents developed MS at an age of 18.74 years significantly (P=0.020)
      greater than their children. Genomic analysis identified 13 variants of TNF-a
      alleles, 7 of TNF-b, 6 of TNF-d and 3 of TNF-e. No differences in the frequencies
      of the various TNF alleles were observed between affected and healthy relatives.
      The two-point lod-score analysis of the TNF locus showed not significant or
      negative results for the TNFalpha loci and slightly positive results (Zmax=0.4 at
      theta=0.2 cM) for the TNFbeta-b locus in the lowest penetrance dominant model.
      The Sib pair analysis, using combined TNFalpha and TNFbeta haplotypes,
      demonstrated a TNF allele sharing between affected sib-pairs which did not exceed
      the expected 50%. These results suggest that genetic factors may partially
      influence the disease onset and the progression rate in sibling pairs. A recall
      bias and/or an 'anticipation phenomenon' could explain the development of MS at
      an older age in parents than in their children. In this small-sized cohort of MS
      Italian families no significant associations were confirmed between TNF
      polymorphism and MS.

PMID- 10202988
TI  - Heterogeneous distribution of amyotrophic lateral sclerosis patients with SOD-1
      gene mutations: preliminary data on an Italian survey.
AB  - We report the absence of superoxide dismutase (SOD-1) gene mutations in 30
      patients with amyotrophic lateral sclerosis (ALS) including individuals with a
      confirmed family history of ALS (familial ALS/FALS), ALS with an unclear family
      history (UFALS) and sporadic ALS (SALS). Single strand conformation polymorphism
      (SSCP) and sequence analysis of the 5 SOD-1 gene exons were undertaken to improve
      the accuracy of the mutation detection. Our preliminary data appear to diverge
      from the results of studies by other groups using different populations. We
      discuss the possible reasons for this disparity and the apparent heterogeneous
      distribution of ALS with SOD-1 gene mutations among different ethnic groups.

PMID- 10202989
TI  - Successful 2-year therapy with systemic interferon-alpha for HTLV-I associated
      myelopathy.

PMID- 10202990
TI  - Failure of endotoxin-free superoxide dismutase to reduce some paw edemas and
      adjuvant arthritis in rats.
AB  - OBJECTIVE AND DESIGN: To elucidate whether superoxide anion plays a major role in
      inflammation models in rats. Endotoxin-free CuZn superoxide (SOD) was used in the
      present study, because we had shown previously that even a trace of endotoxin
      contamination of SOD would carry anti-inflammatory effects. MATERIAL AND
      TREATMENT: Male rats were treated with saline (n=8-10), recombinant human SOD
      (n=8-10), and dexamethasone or indomethacin (n=8-10). METHODS: Foot volume was
      determined by mercury displacement. RESULTS: Two administrations of SOD (5 and 50
      mg/kg), 2 h and just before irritant injection, had no effect on rat paw edema
      induced by phorbol, zymosan or carrageenan. Two administrations of dexamethasone
      (1 mg/kg) or indomethacin (3 mg/kg), 2 h and just before irritation, inhibited
      paw edema significantly (p<0.05). Administration of SOD (10 mg/kg) once daily for
      3 weeks from the day of mycobacterium injection had no effect on injected paw
      swelling and non-injected paw swelling 7, 14, 21 days after irritation.
      Indomethacin (2 mg/kg) once daily for 3 weeks inhibited this arthritis
      significantly (p < 0.05). CONCLUSIONS: Superoxide anion may not play a major role
      in the genesis of inflammation in these rat inflammation models, and endotoxin
      like contaminants may have contributed to some protective effects of SOD
      administration in previous studies.

PMID- 10202991
TI  - Dose-dependence of bacterial lipopolysaccharide (LPS) effects on peak response
      and time course of the immune-endocrine host response in humans.
AB  - OBJECTIVE AND DESIGN: Dose-dependence of lipopolysaccharide (LPS) effects on peak
      and time course parameters of the immune-endocrine host response was examined in
      a placebo-controlled design. SUBJECTS: Data from 42 male volunteers were
      included. TREATMENT: 0.4 or 0.8 ng LPS/kg body weight were applied at 7.00 p.m.
      METHODS: Body temperature, heart rate and leukocyte counts were quantified.
      Plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6),
      adrenocorticotropic hormone (ACTH), cortisol and human growth hormone (hGH) were
      measured. RESULTS: LPS increased significantly the levels of immune (TNF-alpha,
      IL-6) and endocrine (ACTH, cortisol) parameters. HGH secretion was advanced
      without changes in the total amount of hGH released. Dose-dependence of
      endotoxin's effects was significant for neuroendocrine (cortisol) and
      physiological (temperature, heart rate) parameters. Examination of time course
      parameters demonstrated that the higher dose of endotoxin prolonged the increases
      in temperature, IL-6 and cortisol levels. CONCLUSIONS: Our data show that
      increases in the dosage of LPS lead to differential peak responses and changed
      time course patterns of the human host response.

PMID- 10202992
TI  - Determination of the histamine metabolite tele-methylimidazoleacetic acid and of
      creatinine in urine by the same HPLC system.
AB  - OBJECTIVE AND DESIGN: To develop an HPLC method with UV detection for
      determination of tele-methylimidazoleacetic acid (t-MelmAA) in urine of man or
      animals, which is reliable, simple and less expensive than existing GC/MS
      techniques. METHOD: The elaborated procedure enables separation of t-MelmAA from
      its pros-isomer (p-MelmAA) as well as from imidazoleacetic acid. As an internal
      standard tele-ethylimidazoleacetic acid (t-EtlmAA) is used. The acids, after
      being converted to their stable isopropylesters, are extracted at pH 6.0-6.5. The
      further separation prior to HPLC utilises a small cellulose phosphate column. The
      HPLC system is isocratic with a C18 column and mobile phase consisting of an
      aqueous solution of SDS at pH 3.5 mixed with acetonitrile (65:35). An advantage
      of this system is that it can be used to determine the urine creatinine
      concentration to express excreted t-MelmAA in mmol/mol creatinine. RESULTS AND
      CONCLUSIONS: The method applicability is demonstrated in repeated studies in
      mastocytosis patients. The broad range of excretion values, from normal up to a
      high level (0.9 to 30 mmol/mol creatinine), indicates that it can be
      satisfactorily used for evaluation of histamine turnover under various clinical
      conditions. The method appears to be a good alternative to GC/MS based ones.

PMID- 10202993
TI  - Hypothalamic histamine, growth rate, plasma prolactin and growth hormone levels
      in rats with long-term portacaval anastomosis.
AB  - OBJECTIVE AND DESIGN: Histamine can modulate feeding behaviour and hormone
      release; therefore we examined the hypothalamic histamine system, the growth
      pattern and the serum levels of prolactin and growth hormone in rats with
      portacaval anastomosis (PCA). MATERIAL: The growth rate of 30 PCA- and 30 sham
      operated male Han:Wistar rats was monitored for 6 months. Thirteen sham and 9 PCA
      rats were used for biochemical studies. METHODS: Histamine was assayed by HPLC,
      tele-methylhistamine by GC-MS, prolactin and growth hormone by RIA. Student's t
      test was used to compare the groups. RESULTS: Six months after surgery, the PCA
      rats exhibited marked growth retardation (weight gain of 20 g vs. 140 g for the
      sham rats; p < 0.001), increased plasma levels of prolactin (9.7 +/- 2.4 vs. 3.6
      +/- 0.6; p<0.01) and unaltered growth hormone levels (6.2 +/- 0.5 vs. 8.1 +/-
      1.0). A six-fold elevation of histamine concentration (29.5 +/- 3.9 vs. 4.8 +/-
      0.4; p<0.001) and a two-fold increase of tele-methylhistamine levels (1.8 +/- 0.1
      vs. 0.8 +/- 0.02; p<0.001) were found in hypothalamus. CONCLUSION: We suggest
      that increased histaminergic activity in the hypothalamus may be involved in the
      development of growth retardation and in the enhanced basal secretion of
      prolactin in male rats with long-term PCA.

PMID- 10202994
TI  - Ambroxol inhibits the release of histamine, leukotrienes and cytokines from human
      leukocytes and mast cells.
AB  - OBJECTIVES AND DESIGN: The effects of the mucolytic agents ambroxol and N
      acetylcystein (NAC) were studied on the release of histamine, leukotrienes,
      cytokines and superoxide anions from a variety of cells involved in the
      pathogenesis of allergic inflammation. SUBJECTS: Mast cells were isolated from
      human adenoids and skin (n = 5-6). Basophils, monocytes and granulocytes were
      obtained from Buffy-coat blood obtained from healthy blood donors (n = 4-7) and
      enriched by density centrifugation. TREATMENT AND METHODS: Ambroxol or NAC were
      added to the cells for different periods before stimulation with various
      immunological and non-immunological secretagogues. Histamine release from mast
      cells, basophils and monocytes was assayed either by radioimmunoassay or
      spectrofluorometrically. LTC4 (basophils), LTB4 (neutrophil/eosinophil
      granulocytes or monocytes), IL-4 and IL-13 (basophils) were measured by ELISA.
      RESULTS: Ambroxol inhibited histamine release by more than 50% from human
      adenoidal mast cells (1000 microM ambroxol) and skin mast cells (100 microM
      ambroxol) stimulated by Con A and compound 48/80, respectively. Ambroxol (100
      microM) strikingly inhibited anti-IgE induced release of both histamine, LTC4, IL
      4 and IL-13 from basophils and reduced both histamine and LTB4 release induced by
      C5a or Zymosan in monocytes. The drug also reduced LTB4 and superoxide anion
      production in granulocytes stimulated by zymosan or fMLP. In all cell types
      studied, ambroxol was more efficacious following a short preincubation (5-15 min)
      of the drug with the cells before stimulation. In contrast, NAC produced no clear
      effects on any of the different cell types studied, regardless of the
      preincubation period, the concentration or the stimulus employed. CONCLUSIONS:
      Unlike NAC, ambroxol is able to not only inhibit acute mediator release from mast
      cells and leukocytes but also reduce immunomodulatory cytokine generation from
      basophils and may have beneficial effects in the treatment of allergic
      respiratory diseases.

PMID- 10202995
TI  - Serum eosinophil cationic protein (ECP) as a mediator of inflammation in acute
      asthma, during resolution and during the monitoring of stable asthmatic patients
      treated with inhaled steroids according to a dose reduction schedule.
AB  - OBJECTIVE AND DESIGN: The main objective was to establish the level of serum ECP
      in a group of adult asthmatic patients with acute exacerbation and the following
      resolution and in another group of adult, stable asthmatic patients during
      reduction of inhaled steroids. SUBJECTS AND TREATMENT: Acute group: Twenty-one
      asthmatic patients admitted to the asthma clinic with acute deterioration of
      their asthma were set on oral steroids which were reduced to 0 within one week.
      Reduction group: Forty-four stable asthmatic patients on maintenance inhaled
      steroids were included and, on the basis of their peak expiratory flow (PEF)
      values, adjustments in the doses of steroids were made. CONTROL GROUP: Twenty
      stable asthmatics on a constant dose of inhaled steroids were enrolled as
      controls. METHODS: All patients registered daily PEF measurements and spirometry
      was performed at each visit. Blood samples were drawn and analysed for eosinophil
      cationic protein (ECP), myeloperoxidase (MPO), eosinophils and neutrophils.
      RESULTS: ECP was low and within the normal range for all three groups at study
      entry. (Acute group = 8.4 microg/l, reduction group = 3.7 microg/l and control
      group = 4.6 microg/l). Nevertheless, the value in the acute group was
      significantly higher than in the control group (p=0.005). The levels in the acute
      group decreased significantly (p=0.004) after one week on oral steroids. No
      significant changes in ECP were observed in the reduction group or in the control
      group during the follow-up period. The lung function was low in the acute group
      at inclusion, forced expiratory volume in one second (FEV1)=47.1% of predicted,
      and increased significantly during the treatment period (p = 0.006). The patients
      in the reduction- and control group showed small variations in lung function
      during the whole study, FEV1 >70% and PEF > 80% of predicted, respectively. No
      correlation between atopy and ECP was found in the patients irrespective of the
      stage of disease. CONCLUSIONS: This study suggests that the resolution of acute
      asthma exacerbations during treatment could be followed using ECP determinations.
      In stable asthmatics on inhaled steroids and with normal ECP levels, a dose
      reduction could be indicated. A longer period after tapering off steroids is
      proposed to confirm the benefit of ECP measurements for controlling asthma.

PMID- 10202996
TI  - Are bisphosphonates useful in the management of corticosteroid induced
      osteoporosis in transplant patients?

PMID- 10202997
TI  - Gene polymorphism of the renin-angiotensin system and progression of diabetic
      nephropathy.
AB  - Good evidence exists that genetic predisposition is a major determinant in the
      development of renal and cardiovascular complications of diabetes. In particular,
      the role of familial predisposition is well established in diabetic nephropathy
      which may cluster within families, both in type I (IDDM) and in type II (NIDDM)
      diabetes. The genes responsible for predisposition to renal and cardiovascular
      complications are not known, but those of the renin-angiotensin system (RAS) are
      plausible candidates. Beside the large number of studies aimed at evaluating the
      role of polymorphisms in these genes, particularly in angiotensin-converting
      enzyme (ACE) gene, in development of renal disease, no clear-cut evidence has
      been provided until now. Furthermore, a number of trials have shown that ACE
      inhibitors (ACEi) may reduce the rate of progression of renal failure. If the RAS
      genotype were able to foresee the response to ACEi it would provide new
      strategies for a specific treatment of subjects at higher risk.

PMID- 10202998
TI  - Growth hormone and somatostatin in glomerular injury.
AB  - Among other neuropeptides and neurohormones, growth hormone (GH) and somatostatin
      (SRIF) have been shown to modulate the development of glomerular injury in
      various renal diseases. In particular, GH is implicated in the induction of
      glomerular hypertrophy and sclerosis in partial nephrectomy and diabetic
      nephropathy. While GH effects on glomerular hypertrophy are likely mediated by
      insulin-like growth factor I (IGF-I), GH effects on glomerular sclerosis are
      independent of IGF-I. Those effects rather require multiple signaling pathways
      functioning in series, e.g. angiotensin II binding preceding transforming growth
      factor beta (TGF-beta) release, or pro-inflammatory factor release preceding
      repair/scarring processes. In contrast with GH, SRIF administration prevents the
      development of glomerular lesions in experimental diabetes, partial nephrectomy
      and immune glomerulonephritis. Inhibitory effects of SRIF on glomerular
      hypotrophy may be through a decrease in GH secretion and/or IGF-I expression or
      through a direct blockade of glomerular cell proliferation. The mechanisms
      underlying the anti-inflammatory effects of SRIF are most likely a deactivation
      of inflammatory cells related in part to an upregulated response of these cells
      to glucocorticoids. Additional studies will be required to further define the
      role of GH and SRIF in the development of glomerular injury and, hence, to
      identify new targets for a therapeutic approach in glomerular diseases.

PMID- 10202999
TI  - Post-transplantation polyomavirus infections.
AB  - Increasing attention has been recently accorded to BK and JC viruses (BKV and
      JCV). Both these human polyomavirus (HPV) are members of the papovavirus family
      which includes the simian virus SV 40. BKV and JCV infect more than 60% of the
      population worldwide. After primary infection, they remain harboured in the
      kidneys and may become reactivated in situations of immune impairment. HPV were
      first described in 1971. BKV was isolated in a renal transplant patient with
      ureteral stricture and JCV in a patient with progressive multifocal
      leukoencephalopathy (PML). BKV was known to be involved in post-bone marrow
      transplantation (BMT) hemorrhagic cystitis. In renal transplantation, BKV and JCV
      were initially found in the post-transplant ureteric stricture and PML. They are
      now recognised as a possible cause of transplant interstitial nephritis,
      mimicking rejection (satisfying the Banff criteria for acute rejection) or drug
      toxicity. In HPV nephritis there is a mixed interstitial inflammatory infiltrate
      with focal tubular injury; the tubular epithelium shows marked anisonucleosis,
      nuclear atypia and basophilic or amphophilic intranuclear inclusions. Tubulitis
      is frequent. DNA hybridisation or gene amplification by polymerase chain reaction
      usually demonstrate HPV. Although histology with viral nucleic acid detection may
      be helpful in differentiating viral infection and rejection, confusion between
      these complications may lead to either anti-rejection therapy, with the risk of
      over-immunosuppression, or reduction of immunosuppression, with the risk of graft
      loss. Confusion may also arise with inclusions of other viruses, such as
      cytomegalovirus, herpes virus and adenovirus. Reactivation of BKV and JCV
      infection was demonstrated in respectively 22.2% and 10.9% of renal transplant
      recipients and 55% and 6.7% of BMT patients. Unfortunately, no routine screening
      is available for these viruses, so this complication is probably underestimated.
      No specific therapy of HPV infection is currently available.

PMID- 10203000
TI  - IgA nephropathy in cystic fibrosis.
AB  - The kidney does not usually present specific lesions in cystic fibrosis (CF),
      although in recent years renal involvement has been reported, particularly
      amyloidosis and immune complex glomerulonephritis. IgA nephropathy is rare. We
      report four cases of IgA nephropathy out of five renal biopsies performed in the
      last three years in patients with CF and renal involvement and discuss the
      possibility of a relationship between IgA nephropathy and CF.

PMID- 10203001
TI  - Endotoxin concentration in treated water of all hemodialysis units in Greece and
      inquisition of influencing factors.
AB  - Mains and purified water samples from all hemodialysis centers in Greece were
      surveyed to assess hemodialysis water quality and the potential consequences on
      the dialysis population of any microbial and endotoxin contamination. Total
      heterotrophic bacteria counts were estimated employing the pour-plate method, the
      membrane filter technique, for total coliforms, fecal coliforms, enterococci and
      Pseudomonas spp., and the most probable number method for sulfite-reducing
      clostridia. Overall 170 paired samples were tested. Endotoxin concentrations were
      assayed in treated water samples, by the Limulus Amebocyte Lysate method,
      employing a chromogenic substrate. Endotoxin concentration varied from 0-30 EU/ml
      and exceeded 5 EU/ml in 30.6% of the centers. Endotoxin contaminated samples
      showed higher counts of total heterotrophic bacteria, fecal coliforms,
      enterococci and Pseudomonas spp. than the rest of the samples, though the
      difference was significant only for total heterotrophic bacteria and enterococci.
      Additionally, samples with endotoxin contamination derived from the mains water
      had significantly higher counts of fecal coliforms, enterococci and Pseudomonas
      spp. Endotoxin concentration was correlated with the presence of a deionization
      system, counts of fecal coliforms in supply water and counts of total coliforms,
      fecal coliforms and enterococci in treated water. These results demonstrate that
      hemodialysis centers in Greece need to monitor and preventively maintain the
      entire hemodialysis system, in order to ensure renal replacement therapy of good
      quality.

PMID- 10203003
TI  - How pregnancy influences renal function in nephropathic type 1 diabetic women
      depends on their pre-conceptional creatinine clearance.
AB  - Pregnancy in type 1 diabetic women with overt nephropathy can lead to a further
      deterioration in renal function but it is not clear at what level of pre
      conceptional GFR the risk for worsening of renal function begins to increase.
      Therefore we investigated the influence of pregnancy on renal function in 12
      women (14 pregnancies) with pre-conceptional macroproteinuria and near-normal
      creatinine clearance (range 37-93 ml/min/1.73m2). S-creatinine, creatinine
      clearance (CrCL), HbA1c and blood pressure (BP) were measured before conception,
      during each trimester (12th and 24th week of gestation and last week before
      delivery) and three and six months post-partum. In five diabetic women with six
      pregnancies (group A) there was a physiological increase in CrCl of 36% up until
      the 24th week of gestation; their pre-conceptional mean CrCl was 80 (range 70-93)
      ml/min/1.73m2. In seven women with eight pregnancies (group B) CrCl decreased by
      16% during the first two trimesters; the mean CrCl before conception was 61 (37
      73) ml/min/1.73m2. In the last week before delivery CrCl worsened transiently in
      three cases in group A and four in group B, due to pre-eclampsia. Three months
      post-partum the mean CrCl in group A was 78 (70-91) ml/min/1.73m2, approximately
      the same as before pregnancy. In group B the mean CrCl was 39 (22-68)
      ml/min/1.73m2 at this same time; this was 36% lower than the pre-conceptional
      clearance. Mean HbA1c in both groups were approximately the same, but mean BP
      tended to be higher during pregnancy in group B, especially in the week before
      delivery (p<0.05). We conclude that in a high percentage of nephropathic diabetic
      women with significantly low CrCl before conception, renal function worsens
      during and after pregnancy. Inadequate antihypertensive therapy may contribute to
      this.

PMID- 10203002
TI  - The effect of L-carnitine on insulin resistance in hemodialysed patients with
      chronic renal failure.
AB  - We investigated the effect of L-carnitine in seven patients, four female and
      three male (mean age 44.4 +/- 6.0 years) with chronic renal failure. Six
      patients, four female and two male (mean age 49.3 +/- 2.2 years) with chronic
      renal failure were given a placebo (0.9% sodium chloride) as control. After the
      basal data were obtained, patients received a single intravenous dose of L
      carnitine (1 g) or placebo and two hours later insulin sensitivity was studied by
      the intravenous insulin tolerance test. No change was observed in biochemical
      data and K(itt) values in the placebo group. K(itt) increased significantly with
      carnitine (from 2.99 +/- 0.3 to 3.54 +/- 0.2%/min, p < 0.03) compared to the
      control group (p < 0.02). This result suggests that L-carnitine may improve the
      insulin resistance common among uremic patients.

PMID- 10203004
TI  - Inner ear pressure changes modify ADH secretion in freely moving guinea pig.
AB  - The present study was designed to elucidate the relationship between
      endolymphatic pressure and plasma ADH levels in conscious guinea pigs. Plasma ADH
      (pADH) was measured in basal conditions and after having applied positive or
      negative pressure of 20 cmH2O to the inner ear. The experimental protocol was
      designed to avoid any interference on ADH release caused by anesthesia and
      surgical stress. There was no change in blood pressure, heart rate, plasma Na
      (pNa) and osmolality (pOsm) after inner ear pressure (IEP) modifications.
      However, pADH was inversely related with IEP: pADH averaged 31.4 +/- 7.0 pg/ml
      (mean +/- S.D.) in basal conditions, rising to 48.8 +/- 19.3 when IEP was lowered
      and falling to 16.6 +/- 10.3 when IEP was raised. These results confirm that
      structures in the inner ear help control of ADH release.

PMID- 10203005
TI  - N-acetyl-beta-D-glucosaminidase and beta2-microglobulin: prognostic markers in
      idiopathic nephrotic syndrome.
AB  - Increased urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and beta2
      microglobulin (beta2M) is considered a marker of tubulo-interstitial disease.
      This study assessed urinary excretion of NAG and beta2M in children with
      nephrotic syndrome (NS), 14 with cortico-sensitive nephrotic syndrome (CSNS),
      five with cortico-resistant NS (CRNS) and 30 healthy controls matched for sex and
      age. At onset urinary excretion of NAG was significantly higher in children with
      CSNS than controls (p=0.0001) but during remission values were superimposable.
      Conversely in CRNS at onset urinary excretion of NAG and beta2M was significantly
      higher than CSNS and remained unchanged at the end of steroid treatment (p < 0.05
      and p < 0.01). Urinary NAG values in CSNS were correlated with proteinuria (r =
      0.63), serum total proteins (r = -0.54), serum albumin (r = -0.55) and serum
      cholesterol (r = 0.67). These data suggest that urinary excretion of NAG and
      beta2M may be useful as a marker of tubular dysfunction in nephrotic syndromes
      which often characterises cortico-resistant patients.

PMID- 10203006
TI  - Spontaneous hyperthyroidism in an aged male and female Macaca mulatta.
AB  - A 31-year-old male and a 31-year-old female rhesus monkey developed clinical
      signs consistent with hyperthryoidism. These included a ravenous appetite,
      hyperactivity, and accentuated ratchet movement and hand tremors while performing
      fine motor tasks. Bilaterally enlarged thyroid glands were palpated in both
      monkeys. A unique clinical finding of the female as the hypertrophic
      cardiomyopathy. The T3 and T4 levels in the male rhesus were 3.79 ng/ml and 28.20
      microg/dl, respectively. T3 and T4 levels in the female were 4.33 ng/ml and 22.2
      microg/dl, respectively. A biopsy of the enlarged thyroids demonstrated a typical
      multinodular goiter with cystic hyperplasia. The female rhesus was successfully
      treated with methimazole, but the hypertrophic cardiomyopathy did not resolve.
      The relationship between erythrocytosis and T4 levels common to humans and cats
      is also evident in the rhesus monkey.

PMID- 10203007
TI  - Immunohistochemical localization of retroviral-related antigens expressed in
      normal baboon placental villous tissue.
AB  - Endogenous retroviral particles (ERVs) have been detected in the genome of all
      eukaryotes. They are generally non-pathogenic except in mice where they have been
      found to induce tumors and immunological disorders. The ERVs have morphological
      features consistent with type-C retroviral particles and are commonly expressed
      in normal placental villous tissues. ERVs may have a role in the regulation of
      placental gene expression, syncytiotrophoblast formation, or pregnancy-related
      immunosuppression. In this study, well-characterized antibodies (monoclonal and
      polyclonal antibodies) raised against retroviral proteins (anti-HIV and anti-SIV)
      and endogenous retroviral (ERV) particles were assessed for their cross
      reactivity (by using immunohistochemistry) with normal baboon placental and other
      adult tissues. The monoclonal antibodies to exogenous retroviral proteins (anti
      HIV-2 gp120, anti-HIV-1 gp41, anti-SIVmac p27, anti-HIV-1 RT, and anti-HIV-2 core
      protein) showed specific immunohistochemical reactivity with the
      syncytiotrophoblast. Antibodies to endogenous retroviral gene products (anti-ERV3
      env, anti-HERV-K RT, and anti-HERV-K env) also reacted in a similar manner and
      did not cross-react with other adult tissues. These studies have shown that
      retroviral-cross-reactive proteins are expressed in baboon placental
      syncytiotrophoblast and may have a role to play at the feto-maternal interface.

PMID- 10203008
TI  - Study of prenatal growth in the capuchin monkey (Cebus apella) by ultrasound.
AB  - Capuchin monkey (Cebus apella) is a new world primate that in recent years has
      become important in biomedical research. The purpose of this study was to
      establish and correlate normal fetal growth parameters with gestational age in
      capuchin monkeys. In seven pregnant animals serial ultrasonic assessment of
      gestational sac (GS), embryo/fetal greatest length (GL), biparietal diameter
      (BPD), thorax height (TH), and femur length (FL) were performed. Identification
      of the GS was possible on day 23+/-2.8 (X +/- SE). The embryo and its heartbeat
      was detected on day 32.7+/-2.8, the GL being measurable thereafter. By day 45.4+/
      1.4 BPD and TH were measurable. FL could only be measured from day 70.6+/-2.1.
      Predictive regression equations of gestational age (GA) were modeled with data
      obtained. In addition, preliminary data of fetal heart rate showed a decrease in
      frequency with advancing gestation.

PMID- 10203009
TI  - The central and renal hemodynamic effects of amino acid infusion in the study of
      renal reserve in the baboon.
AB  - Normal human renal function is characterized by a large renal reserve.
      Recruitment of this reserve is a compensatory and pathological response to renal
      injury. This study was designed to assess the renal reserve and central
      hemodynamics of young female baboons and, in doing so, the appropriateness of the
      use of these animals in a model of human renal disease. Eight female baboons
      completed the protocol. PAH and inulin clearances were measured before and after
      an amino acid infusion. Central hemodynamics were measured with arterial and
      pulmonary artery catheters. Effective renal plasma flow and glomerular filtration
      rate increased by 42% after amino acid infusion (P = .025). Expansion of renal
      function was not consistent among individual baboons; two of the eight animals
      did not demonstrate renal reserve. Central hemodynamics were unaffected by the
      protocol.

PMID- 10203010
TI  - Intestinal cryptococcosis in a common marmoset (Callithrix jacchus).
AB  - A five-year-old female common marmoset (Callithrix jacchus) died after a one
      month clinical course of nonspecific signs. Pathologic findings were acute
      diffuse fibrinonecrotizing enteritis and granulomatous endolymphangitis of
      intestinal and mesenteric lymphatic vessels. Both lesions were associated with a
      marked proliferation of Mayer's mucicarmine-positive, 4 to 15 microm yeasts that
      were surrounded by a wide clear halo. The infection was probably acquired by oral
      route. Other findings included moderate multifocal granulomatous and necrotizing
      hepatitis and mesangial nephropathy. Although the immunological status of this
      marmoset was unknown, cryptococcosis might induce primary lethal intestinal
      infections in callitrichids.

PMID- 10203011
TI  - Review of exertional rhabdomyolysis and a case in a rhesus monkey (Macaca
      mulatta).
AB  - This is the first confirmed report of exertional rhabdomyolysis in a non-human
      primate. The monkey was singly housed and presented with anorexia and reluctance
      to move. There was no external evidence of trauma. Clinicopathologic findings
      included mild azotemia, marked elevation in serum creatine phosphokinase (CPK),
      alanine aminotransferase, aspartate aminotransferase, and myoglobinuria. Two days
      post-incident, the peripheral skeletal muscle had marked multifocal myonecrosis
      and fibrillar disruption without an inflammatory reaction. Treatment included
      diuresis and pain relief, and urinary output was monitored. The monkey recovered
      over the next two weeks. The major significance of skeletal muscle damage is the
      potential of released myoglobin to cause acute renal failure in the presence of
      other co-factors such as hypovolemia, acidosis, or ischemia. CPK levels can be
      highly variable and are inconsistent with the degree of muscle damage; however,
      CPK is thought to be the most sensitive enzyme marker for muscle necrosis.
      Because of the potential life-threatening sequelae, exertional rhabdomyolysis
      should be included as a differential diagnosis when similar clinical and
      pathological signs are observed.

PMID- 10203013
TI  - Gastrointestinal tumors observed in nonhuman primates at the German primate
      center.
AB  - Twenty-six gastrointestinal tumors were observed in twenty-three nonhuman
      primates during routine necropsies at the German Primate Center, Gottingen. The
      majority (15 cases) were colorectal mucoid adenocarcinomas in cotton-top tamarins
      (Saguinus oedipus), which in two animals were associated with gastric adenomas.
      Three cases of small intestinal mucoid adenocarcinomas occurred in common
      marmosets (Callithrix jacchus). One colonic leiomyoma was observed in a dwarf
      galago (Galagoides demidovii) and another one in a cotton top tamarin. Singular
      findings were a tubular adeno-carcinoma of the ileo-caecal valve in a saddle
      backed tamarin (Saguinus fuscicollis) and a lymphosarcoma of jejunum, ileum, and
      colon in another saddle-backed tamarin. Multiple tubular adeno-carcinomas of the
      colonic diverticles occurred in an aged rhesus monkey (Macaca mulatta). The
      findings are discussed in comparison to the situation in man.

PMID- 10203012
TI  - Retinoid teratogenicity in the macaque: verification of dosing regimen.
AB  - To further define teratogenicity associated with 13-cis-retinoic acid (13-cis-RA)
      in the cynomolgus monkey, the drug was orally administered on three different
      treatment regimens. Experiment (Exp.) 1 (2.5 mg/kg/day, gestational day [GD] 12
      27, n = 11) investigated the teratogenicity of a single daily dose of 13-cis-RA
      administered shortly after embryo implantation. Pharmacokinetic sampling was done
      to determine retinoid profiles on the first (GD12) and last (GD27) days of
      treatment. Exposure to 13-cis-RA during early organogenesis in Exp. 2 (2.5
      mg/kg/day, GD20-27, and 2 x 2.5 mg/kg/day, GD28-30, n = 5) investigated the
      potential adverse effects of 13-cis-RA on the developing limb. The use of
      multiple doses of 13-cis-RA in Exp. 3 (2 x 2.5 mg/kg/day, GD26-27, n = 5)
      investigated the necessity of double dosing on the induction of retinoid
      embryopathy in the macaque. Malformations of retinoid target organs as well as
      embryolethality were most prevalent when single daily doses of 13-cis-RA were
      administered during pre- and early organogenesis in Exp. 1. Moreover, multiple
      doses on GD26-27 failed to induce any manifestation of abnormal development in
      Exp. 3. These results confirm that the lowest observed adverse effect level
      (LOAEL) in macaques is 2.5 rather than 5.0 times greater than that observed in
      human pregnancies. Exposure during forelimb development (GD20-30) in Exp. 2 was
      unsuccessful in inducing defects of this skeletal region, although defects in
      several retinoid target organs (i.e., cerebellum and internal ear) were present,
      indicating that a teratogenic threshold was achieved. Pharmacokinetic analysis of
      13-cis-RA and its metabolites on GD12 and 27 in Exp. 1 showed considerable
      exposure to the administered drug and its 4-oxo-metabolite. In contrast, the
      exposure to all-trans-RA was negligible. The results support the use of a
      specific treatment schedule in early gestation in the macaque as the most
      appropriate model for characterizing the teratogenic potential of retinoids in
      humans.

PMID- 10203015
TI  - The South Amerindian allotype HLA-B*3909 has the largest known similarity in
      peptide specificity and common natural ligands with HLA-B27.
AB  - HLA-B*3909 has only been found among South Amerindians, and presumably arose
      locally in these populations. It differs from B*3901 by a single Tyr to Ser
      change at position 99. To analyze the influence of this polymorphism on peptide
      specificity, pool sequence analysis and sequencing of multiple individual ligands
      from B*3901 and B*3909 were carried out. Both allotypes bind peptides with Arg2
      or His2 and nonpolar C-terminal residues. However, whereas His2 is the
      predominant B*3901 motif, a majority of the B*3909-bound peptides have Arg2. In
      addition, B*3909 binds peptides with Pro2, and also shows an increased preference
      for Pro3. In spite of their differences, both subtypes bind overlapping peptide
      repertoires, as indicated by the identification of several identical ligands from
      their respective peptide pools. B*3909 is significantly more similar in its
      peptide specificity to HLA-B27 than B*3901. This is due to the increased
      preference of B*3909 for Arg2 and to low suitability of HLA-B27 for His2. The
      similarity between HLA-B27 and B*3909 was confirmed by identification of a
      natural ligand common to both allotypes. In addition, multiple HLA-B27 ligands
      bound efficiently B*3909 in vitro. The results indicate that, among the HLA class
      I allotypes of known peptide specificity, B*3909 is the most similar in its
      peptide binding properties to HLA-B27, which is absent in South Amerindians. This
      may have implications for the susceptibility of individuals in these populations
      to spondyloarthropathies.

PMID- 10203014
TI  - The origin of Cretan populations as determined by characterization of HLA
      alleles.
AB  - The Cretan HLA gene profile has been compared with those of other Mediterranean
      populations in order to provide additional information regarding the history of
      their origins. The allele frequencies, genetic distances between populations,
      relatedness dendrograms and correspondence analyses were calculated. Our results
      indicate that the Indoeuropean Greeks may be considered as a Mediterranean
      population of a more recent origin (after 2000 B.C.), while all other studied
      Mediterraneans (including Cretans) belong to an older substratum which was
      present in the area since pre-Neolithic times. A significant Turkish gene flow
      has not been detected in the Greek or Cretan populations, although Greeks and
      Turks have two high frequency HLA-DRB-DQB haplotypes in common. It is proposed
      that Imazighen (Caucasoid Berbers living at present in the North African coast
      and Saharan areas) are the remains of pre-Neolithic Saharan populations which
      could emigrate northwards between about 8000-6000 B.C., when desert desiccation
      began. They also could be part of the stock that gave rise to Sumerians, Cretans
      and Iberians; this is supported by both linguistic and HLA genetic data.

PMID- 10203016
TI  - Susceptibility to ankylosing spondylitis is independent of the Bw4 and Bw6
      epitopes of HLA-B27 alleles.
AB  - We have characterized HLA-B27 alleles in a sample of the population from the
      Azores (n=46) with the aim of investigating the contribution of different
      subtypes to ankylosing spondylitis (AS). The study was carried out using PCR-SSOP
      and in some samples genomic sequencing was conducted. Some significant new
      finding have arisen from this study. First, B*2705,B*2702,B*2703,B*2707 and
      B*2708 alleles were found to be represented in this population. The polymorphism
      of B27 alleles found in a sample of the population from the Azores is higher than
      the Caucasian groups described. B*2703 and B*2707 have not previously been
      described to be represented in Caucasians and this could indicate admixtures with
      different populations of the world. In addition, the B*2708 allele was found to
      be associated with AS in a large family from the Azores. This association has not
      been previously reported in either ethnic group and needs to be confirmed in
      other population studies. This is of considerable interest since has only been
      described as a rare subtype underrepresented in the British population and has
      not been previously found to be associated with AS. B*2708 carries the sequence
      specifying the Bw6 epitope in contrast to most B27 alleles which carry a Bw4
      sequence. Differences in this region (residues 77-83) can alter the F-pocket and
      affect T-cell recognition. The importance that these molecular changes can play
      in the pathogenesis of AS is discussed.

PMID- 10203017
TI  - Aberrant splicing of intron 1 creates a novel null HLA-B*1501 allele.
AB  - A comparison of serological and DNA HLA class I typing data identified a
      serological "blank" HLA-B15 antigen in a volunteer donor on the bone marrow
      registry. Isoelectric focusing and Western blot analysis of a cell line
      established from this individual confirmed that the HLA-B15 antigen is not
      expressed at the cell surface. Nucleotide sequence analysis of the HLA-B*15 null
      allele revealed a 10-bp deletion near the 3' end of intron 1, when compared to
      the normal HLA-B*1501 sequence. All of the HLA-B*15 specific cDNA clones examined
      retained the intron 1 sequence. Reverse transcription-polymerase chain reaction
      (RT-PCR) and Southern blot analysis demonstrated that the HLA-B*15 mRNA molecule
      contained the intron 1 sequence, indicating an inability to efficiently splice
      out intron 1 from the mRNA transcript. The retention of the mutated intron 1
      sequence in the mRNA causes a frameshift and premature termination of translation
      at the start of exon 2, explaining the HLA-B*1501 null phenotype. Our data
      predicts that the HLA-B*1501 null allele would express a small truncated protein
      containing the signal sequence fused to an ORF within intron 1 and terminating
      (out of frame) just within exon 2.

PMID- 10203018
TI  - Beta2-micro-free HLA class I heavy chain levels in sera of healthy individuals.
      Lack of association with beta2-micro-associated HLA class I heavy chain levels
      and HLA phenotype.
AB  - We have applied a double-determinant immune assay (DDIA) to measure soluble beta2
      microglobulin (beta2-micro)-free HLA class I heavy chains in serum. The mean
      concentration of beta2-micro-free HLA class I heavy chains in serum from 120
      healthy subjects was 0.21+/-0.24 microg/ml. The individual serum levels of beta2
      micro-free HLA class I heavy chains had a wide distribution, did not seem to be
      related with HLA phenotype, were stable over time and did not change with age.
      The serum levels of soluble beta2-micro-free HLA class I heavy chains did not
      correlate with those of soluble beta2-micro-associated HLA class I heavy chains,
      suggesting that their release is independently regulated. Three forms of soluble
      beta2-micro-free HLA class I heavy chains, with apparent molecular masses of 44,
      39 and 37-35 kD, respectively, circulate in human serum. These results provide a
      useful background to assess the serum level of soluble beta2-micro-free HLA class
      I heavy chains in pathological conditions and to evaluate their putative
      immunoregulatory function.

PMID- 10203020
TI  - HLA-DR-DQ alleles and HLA-DP alleles are independently associated with
      susceptibility to different stages of post-schistosomal hepatic fibrosis in the
      Chinese population.
AB  - Abstract: Evaluation of human leukocyte antigen (HLA) class I and class II genes
      was performed on patients from China with Schistosomiasis japonica. Patients were
      categorized as grade 0 (n=44), grade I (n=81), grade II (n=99), or grade III
      (n=6) based on increasing severity of hepatic fibrosis due to repeated
      Schistosoma japonicum infections. These results show that the HLA-DRB1*1101
      DQA1*0501-DQB1*0301 (Pc<0.02) and HLA-DRB1*1501-DRB5*0101 (Pc<0.02) haplotypes
      are associated with protection and susceptibility to grade I fibrosis,
      respectively, and that the HLA-DPA1*0103 -DPB1*0201 haplotype (Pc<0.02) is
      associated with protection from both grade II and III severe fibrosis. There was
      no association between HLA-B DNA haplotypes and the disease. These findings
      indicate that the HLA-class II molecules play a role in preventing or promoting
      fibrotic liver change after deposition with Schistosome eggs. Moreover, a
      tendency was observed within the HLA class II genes for the HLA-DR-DQ alleles to
      be associated with protection against early changes in liver fibrosis, whereas
      HLA-DP alleles were associated with protection from the late phase of fibrosis or
      severe hepatosplenic schistosomiasis.

PMID- 10203019
TI  - HLA-A33 and -B44 and susceptibility to postherpetic neuralgia (PHN).
AB  - HLA class I and class II alleles of 32 Japanese patients with postherpetic
      neuralgia (PHN) and 136 healthy controls were analyzed by serological (class I)
      and DNA (class II) typing for any significance in the susceptibility to varicella
      zoster virus (VZV). We recognized positive associations of the development of PHN
      with the HLA class I antigens HLA-A33 and -B44, and the HLA-A33-B44 haplotype.
      This haplotype is tightly linked to DRB1*1302 in a Japanese healthy population.
      However, no significant association between PHN and HLA class II alleles was
      observed with no linkage of the HLA haplotype HLA-A33-B44 to HLA-DRB1*1302 in the
      patients with PHN. These findings suggest that HLA class I gene may genetically
      control the immune response against VZV in the pathogenesis of PHN.

PMID- 10203021
TI  - HLA-B locus sequence-based typing.
AB  - We describe an approach for HLA-B high-resolution typing. A single locus-specific
      amplification generates a 1-kb fragment useful for direct sequencing. Four
      internal primers are necessary for exon 2 and 3 cycle-sequencing in both
      directions. Fluorescent dye-labelled nucleotides are incorporated during cycle
      sequencing and reaction products are analyzed in an automated DNA sequencer. At
      present, software programs allow automatic assignment of exon 2 only; analysis of
      exon 3 is not automatic. In the future, the development of more sophisticated
      software will improve allele assignment. The approach described in this work
      offers a precise and efficient identification of known allele sequences and at
      the same time can differentiate new alleles. Furthermore, it may be applied as a
      model for the development of similar molecular typing approaches for other
      polymorphic HLA loci.

PMID- 10203022
TI  - Tissue distribution of the mRNA for a rhesus monkey major histocompatibility
      class Ib molecule, Mamu-AG.
AB  - We identified recently a novel major histocompatibility complex (MHC) class I
      locus in the rhesus monkey, Mamu-AG, which is expressed in the placenta and
      encodes molecules that share unique characteristics of human HL4-G. We
      established locus-specific reverse transcription-polymerase chain reaction (RT
      PCR) and ribonuclease protection assays to determine whether Mamu-AG is expressed
      in other rhesus monkey tissues. With an RT-PCR assay, Mamu-AG mRNA was detected
      in placenta, amniotic membranes, kidney, spleen, eye, brain, lung, spinal cord,
      liver and occasionally heart, but was undetectable in lymph nodes, salivary
      glands, peripheral blood lymphocytes (PBL), large and small intestine, skeletal
      muscle or skin. Examination of endocrine organs demonstrated the presence of Mamu
      AG transcripts in pituitary, testes, ovary and adrenal glands but not in pancreas
      or thyroid. Quantitative analysis using a ribonuclease protection assay
      demonstrated that the highest level of Mamu-AG mRNA expression was consistently
      in the placenta and amniotic membranes, while expression was moderate in a few
      tissues (testis, adrenal) and low to undetectable in all other tissues. These
      results suggest that the Mamu-AG mRNA, like the mRNA for the human MHC class Ib
      gene HLA-G, is expressed at high levels in the placenta, but also has restricted
      low-level expression in other tissues.

PMID- 10203023
TI  - Cell surface expression of HLA-E molecules on PBMC from a TAP1-deficient patient.
AB  - It was recently revealed from studies on TAP-deficient cell lines that HLA-E
      molecules are associated with nonamer peptides derived from certain HLA class I
      leader sequences and are expressed on the cell surface in a TAP-dependent manner.
      We have previously reported a homozygous TAP1 gene mutation in a HLA class I
      deficient patient. In the present report, we demonstrate HLA-E molecule
      expression on the surface of the peripheral blood mononuclear cells (PBMC) of the
      TAP1-deficient patient. The HLA-E expression level on the monocytes of the
      patient was as high as that in healthy donors, whereas the HLA-E expression level
      on the lymphocytes of the patient was slightly lower. On the other hand, HLA-E
      expression was not detected on KMW-B2 cells, an Epstein-Barr virus (EBV)
      transformed B-cell line derived from the lymphocytes of the TAP1-deficient
      patient. These data suggest the existence of TAP-dependent and -independent
      pathways for the surface expression of HLA-E molecules.

PMID- 10203024
TI  - CTLA4 polymorphisms in Spanish patients with rheumatoid arthritis.
AB  - Cytotoxic T-lymphocyte antigen 4 (CTLA4) polymorphisms located in the promotor
      region at positions -318 (C/T) and in exon 1 (49 A/ G) were investigated in 138
      Spanish patients (37 men and 101 women) with rheumatoid arthritis and in 305
      ethnically-matched healthy controls. When the allelic and genotypic frequencies
      corresponding to the CTLA4 -318 position were compared, no significant
      differences between patients and controls were found. However, when the CTLA4 49
      A/G polymorphism was analysed, a significant increase of A/G heterozygous
      individuals among female patients (48.5% vs. 33.8% in controls; P=0.008; OR=2.0)
      was observed. This increase was absent among males (37.8%, P=NS). Analysis of the
      CTLA4 49 polymorphism with respect to HLA-DRB1 typing demonstrated a significant
      increase of A/G heterozygosity in the HLA-DR3-positive patient group compared
      with HLA-DR3-negative patient group (14/19, 74% vs. 49/119, 41%; P=0.009,
      OR=4.0). The increase of A/G genotype among HLA-DR3-positive patients was found
      in both males (4/6, 67%) and females' (10/13, 77%), although statistical
      differences were only reached in the female group. These results provide new
      insight into this complex association, confirm previous data from other studies,
      and suggest that the CTLA4 gene could be involved in the pathogenesis of
      rheumatoid arthritis.

PMID- 10203025
TI  - Fluorotyping of HLA-DRB by sequence-specific priming and fluorogenic probing.
AB  - Similar to our recently described HLA-A and -C fluorotyping strategies, the aim
      of this study was to develop a sequence-specific primed polymerase chain reaction
      (PCR-SSP)-based fluorotyping method for HLA-DRB. Applying the fluorogenic 5'
      nuclease assay, it is possible to increase the sample throughput rate by
      abolishing all labor-intensive post-amplification steps. Additionally, problems
      related to contamination are eliminated. The method relies on the 5'-3'
      exonuclease activity of the Taq-DNA Polymerase which cleaves a target-specific
      and individually labelled fluorogenic probe during successful PCR. Different
      labelled probes specific for different targets can be applied in a single PCR,
      allowing independent detection of the specific HLA and the internal control
      product. The probe used to detect the HLA-DRB specific amplicons was labeled at
      its 5' end with FAM as the reporter and further 3' with TAMRA as the quencher.
      The probe hybridized within the 2nd exon to a conserved region which was covered
      by all primer mixes. In case of amplification, the cleavage of the fluorogenic
      probe led to an interruption of the TAMRA-mediated quenching effect and generated
      a significant increase of the FAM fluorescence. The HLA-DRB fluorotyping
      information was based on the FAM fluorescence released by 24 individual primer
      mixes. A TET-TAMRA-labelled probe was used to indicate amplification of the
      internal control sequence in each PCR reaction. So far, 170 PCR typed clinical
      samples representing all serologically defined HLA-DRB specificities were
      analyzed using this fluorotyping method. The results were 100% concordant with
      those obtained by conventional agarose gel detection.

PMID- 10203026
TI  - Identification of a novel DRB1-allele (DRB1*0106) by sequence-based typing.
AB  - We report herein the identification of a new DRB1 allele using sequence-based
      typing. The new allele, DRB1*0106, was detected during routine HLA typing of a
      patient undergoing bone marrow transplantation. DRB1*0106 is identical to
      DRB1*0101 except for two codons, 71 (AGG-->GCG) and 86 (GGT-->GTG), changing the
      encoded arginine to alanine and glycine to valine. Both sequences were confirmed
      by polymerase chain reaction with sequence-specific primers (PCR-SSP). The
      polymorphism at codon 71 has not been, until now, identified in DRB1*01 alleles,
      although it is present in all the DRB1*15 alleles as well as DRB1*1309 and
      DRB1*1424.

PMID- 10203027
TI  - Lentivirus tropism and pathogenesis.

PMID- 10203028
TI  - Broadly cross-reactive HIV-specific cytotoxic T-lymphocytes in highly-exposed
      persistently seronegative donors.
AB  - HIV-specific cytotoxic T-lymphocytes (CTL) are believed to play a key part in the
      control of virus levels throughout HIV infection. An important goal of a
      potential prophylactic vaccine against HIV is therefore to elicit a strong CTL
      response which is broadly cross-reactive against a diverse range of HIV strains.
      We have detected HIV-specific CTL in two groups of highly-exposed but
      persistently seronegative female sex workers in Africa which show extensive cross
      reactivity between different viral sequences. In a small group of women exposed
      to both HIV-1 and HIV-2 in Gambia, studied over 4 years, we have repeatedly
      detected HLA-B35-restricted CTL which exhibit cross-reactivity between the HIV-1
      and HIV-2 sequences of the CTL epitopes. In women with particularly intense
      exposure to what are likely to be multiple clades of HIV-1 in Nairobi Kenya, we
      have detected CTL directed towards epitopes conserved between HIV-1 clades. In
      neither group is there any evidence that variation in CCR5 sequence or expression
      is responsible for their apparent resistance to HIV infection. However, in
      seropositive donors from Oxford infected with African strains of HIV-1, we have
      defined CTL responses which are specific for particular clades and have mapped
      some unique A clade CTL epitopes, together with others to highly-conserved
      regions of the virus. Further information about the extent of cross-reactive CTL
      immunity will be important for future vaccine design and evaluation.

PMID- 10203029
TI  - Cellular immunity and target cell susceptibility in persons with repeated HIV-1
      exposure.
AB  - We prospectively studied 37 HIV-1 uninfected persons engaging in repeated high
      risk sexual activity with an HIV-1 infected partner, as well as 18 of their
      infected partners. Only one subject (3%) demonstrated the homozygous 32-bp
      deletion delta32delta32 of the HIV-1 co-receptor CCR5. CD4+ cells from all high
      risk subjects except the delta32delta32 CCR5 homozygote were susceptible in vitro
      to both CCR5-dependent and CXCR4-dependent HIV-1 strains. Median HIV-1 plasma RNA
      levels of the infected partners were not significantly different from levels of
      matched infected controls. Thirteen subjects demonstrated HIV-1 specific CTL at
      one or more visits, and these activities were more commonly observed in persons
      with the wild type CCR5 genotype. These results indicate that cellular immunity
      rather than inheritance of the delta32 CCR5 mutation accounts more often for
      persistently HIV-1-resistant cases.

PMID- 10203030
TI  - A role for mucosal immunity in resistance to HIV infection.
AB  - In a recent, thought-provoking novel by Elizabeth McCracken (The Giant's House.
      Avon Books, New York, 1997), two characters discuss love and its impossibilities.
      One brashly claims to be "immune to love", explaining the concept to his
      perplexed interlocutor, "...people become immune to love like they become immune
      to any disease. Either they had it bad early in life, like chicken pox and that's
      that; or they keep getting exposed to it in little doses and build up an
      immunity; or somehow they just don't catch it, something in'em is born resistant.
      I'm the last type. I'm immune to love and poison ivy". (p. 275) (E. McCracken,
      The Giant's House. Avon Books, New York, 1997). Substitute the words 'HIV
      infection' for 'love' and this intriguing metaphor summarizes the state of the
      art working hypotheses for the phenomenon of resistance to HIV infection in HIV
      exposed individuals who, against all odds, do not seroconvert. These hypotheses
      will be discussed hereafter and particular emphasis will be placed upon a
      possible role for mucosal immunity in this phenomenon.

PMID- 10203031
TI  - Resistance to HIV-1 infection among highly exposed sex workers in Nairobi: what
      mediates protection and why does it develop?
AB  - Variability in susceptibility to infection and disease caused by infectious
      agents is a characteristic of all populations. Among susceptible individuals
      exposed to an infection, not all become infected and among infected individuals,
      not all develop disease. It seems logical that variability in susceptibility to
      infection and disease would apply to infection and disease with human
      immunodeficiency viruses. However, until recently, it has been generally held
      that there is no natural immunity to HIV-1 and that once infected, all
      individuals would ultimately succumb to AIDS.

PMID- 10203032
TI  - Control mechanisms of virus replication in naturally SIVsmm infected mangabeys
      and experimentally infected macaques.
AB  - As a close cousin to Asian macaques, the African sooty mangabey monkey, a species
      naturally infected with SIV without ever developing disease, represents an
      intriguing and thought provoking model for the study of lentiviral infection and
      disease development. Pursuant to our previous findings that documented the
      presence of high frequencies of CD8+ T-cells capable of inhibiting lentiviral
      replication in vitro via a soluble factor, the potential contribution of beta
      chemokines and their receptor was evaluated in samples from sooty mangabeys and
      disease susceptible macaques. Both mangabey and Rhesus macaque PBMC were found to
      secrete comparable levels of MIP-1alpha, MIP-1beta and RANTES after stimulation
      in vitro. Constitutive expression of CCR-5 appeared lower in mangabey PBMC but
      the vast majority of T-cells from mangabeys or macaques were found to express CCR
      5 after in vitro activation. Sequence analysis of macaque and mangabey MIP-1alpha
      and RANTES showed complete homology to the human counterpart. MIP-1beta on the
      other hand while highly conserved among both monkey species, showed only 93%
      homology to human MIP-1beta. In addition, CCR-5, CCR-2b and CXCR-4 presented no
      consistent differences between rhesus and mangabey sequences. Thus, based on
      current data, differences in disease susceptibility between macaques and
      mangabeys do not appear to rely on differences in chemokine pathways. However,
      analyses of the ontogeny of CD8+ T-cell-mediated inhibition of SIV replication
      showed that macaque PBMC acquire this function shortly after infection, and show
      a progressive loss thereafter, correlated with progression towards disease.
      Mangabeys, on the other hand, appear to acquire the CD8+ T-cell inhibitory
      function long before any evidence of seroconversion to SIV and maintain this
      function for the lifetime of the animal. In vitro analyses of induction of the
      CD8+ inhibitory function showed that rhesus CD8+ T-cells have the potential to
      secrete the inhibitory factor(s) prior to SIV infection.

PMID- 10203033
TI  - Why are the natural hosts of SIV resistant to AIDS?
AB  - An increasing number of African primate species have been shown to be infected in
      the wild with their own distinct variants of simian immunodeficiency virus. The
      most striking feature of these natural host systems is the lack of AIDS-like
      disease despite long-term infection. In the African green monkey (AGM)/SIVagm
      system there is no evidence that a vigorous antiviral immune response, a lack of
      variability or a low virus load accounts for this lack of pathogenicity. New-born
      AGMs appear to be even more resistant to the virus than adults, despite their
      immature immune system and higher pool of target cells. The fact that AGMs,
      unlike HIV-infected humans, lack a humoral immune response to non-denatured Gag
      protein and do not show trapping of virus in the lymph nodes suggested that
      tolerance to Gag might prevent the formation of immune complexes which would
      normally be filtered out by the lymphoid tissues with detrimental results. This
      apparent tolerance to Gag is a common feature of many, if not all, of the natural
      host systems and might explain why the lymph nodes and immune system in general
      remain intact in these primates in the face of continuous, high level virus
      replication.

PMID- 10203034
TI  - Rapid and slow progressors differ by a single MHC class I haplotype in a family
      of MHC-defined rhesus macaques infected with SIV.
AB  - Highly polymorphic HLA class I molecules may influence rates of disease
      progression of HIV-infected individuals. Recent evidence suggests that
      individuals who mount vigorous CTL responses to multiple HIV-1 epitopes have
      reduced viral loads, and survive longer than individuals that make a less robust
      or less diverse CTL response. It has been difficult, however, to define
      associations between particular HLA class I alleles and rates of disease
      progression. This may be due, in part, to the uncontrolled variables associated
      with naturally acquired HIV infections. Studies using MHC-defined, non-human
      primates infected with well characterized viral stocks should help to clarify
      this relationship. To explore the possibility that MHC class I polymorphism can
      influence disease progression, we infected four Mamu-DRB-identical individuals
      from a family of MHC-defined rhesus macaques intravenously with 40
      TCID50SIVmac239. Two of these macaques developed severe wasting and were
      euthanized within 80 days of infection, while the other two survived for more
      than 400 days without showing any symptoms of disease. Since all four of these
      macaques were Mamu-DRB-identical, we were able to exclude the MHC class II DRB
      loci as determinant of disease progression. Interestingly, both of the slow
      progressors made CTL responses to the same three SIV CTL epitopes, which were
      restricted by two molecules (Mamu-B*03 and B*04) encoded by their common maternal
      haplotype. The two rapid progressors did not share this haplotype with the slow
      progressors, and we were unable to detect CTL responses in these two siblings.
      These observations implicate products of the Mamu-B*03 and B*04 alleles in
      resistance to disease progression in this family of SIV-infected macaques, and
      provide additional evidence that certain MHC class I-restricted CTL responses may
      play a significant role in delaying the onset of AIDS.

PMID- 10203035
TI  - Differential cytotoxic T-lymphocyte (CTL) responses in HIV-1 immunised sibling
      chimpanzees with shared MHC haplotypes.
AB  - Cell mediated immune responses to HIV-1 and CTL responses in particular differ
      dramatically in infected individuals. This may largely be influenced by the
      immunogenetic differences of different individuals such as those encoded by the
      MHC. These differences may be difficult to dissect due to the immunosuppressive
      nature of HIV-1 infection itself. In order to reduce the variables associated
      with effects of the virus, one recombinant viral antigen was chosen from a
      particular HIV-1 variant (rgp120 of the clinical isolate HIV-1w6.1D). To minimise
      differences between outbred hosts, we chose two sibling chimpanzees from which
      the family pedigree and genetic segregation with respect to polymorphic MHC
      molecules was known. Immunisation induced strong antigen specific antibody and T
      helper immune responses. The magnitude and persistence of the humoral and T
      helper immune responses were comparable in both chimpanzees. However, CTL
      responses were only observed in one sibling. These responses were subsequently
      mapped to several distinct epitopes. The CTL response to the immunodominant
      epitope was found to be presented in the context of a MHC molecule which was
      shared by both siblings. The absence of a CTL response in the other sibling is
      not yet understood, but could not be attributed to MHC alleles that were not
      shared by these two chimpanzees. These findings suggest that other polymorphic
      immunoregulatory mechanisms such as those involved in antigen processing and
      presentation influence host CTL responses to HIV-1.

PMID- 10203036
TI  - HIV-1 infectability of CD4+ lymphocytes with relation to beta-chemokines and the
      CCR5 coreceptor.
AB  - CD4+ lymphocytes exhibit variable permissiveness to the replication of HIV-1. A
      cohort of sexually-exposed-yet-uninfected individuals were previously shown to
      have CD4+ lymphocytes refractory for M-tropic viral replication. In particular,
      two individuals from this population whose CD4+ lymphocytes exhibited complete
      resistance to M-tropic viral replication were later shown to be homozygous for a
      32bp (delta32) deletion in the gene encoding for CCR5. In screening diverse
      populations, HIV-1 infected individuals heterozygous for the delta32 allele were
      statistically favored in their disease course to harbor lower viral loads and
      exhibit slower rates of CD4+ cell loss when compared to control CCR5 wild-type
      individuals. Further comparative analysis between individuals in the exposed but
      uninfected cohort who demonstrated intermediate levels of in vitro viral
      replication and CD4+ lymphocytes isolated from uninfected delta32 heterozygous
      individuals indicate that reduced levels of in vitro M-tropic replication are a
      CCR5-related phenomenon: CD4+ lymphocytes from these individuals were more
      sensitive to the HIV-1 blocking effects of recombinant chemokines, displayed
      lower CCR5 cell surface expression levels and a proportionate increase in the
      production of RANTES when compared to CD4+ lymphocytes from control individuals.
      These results suggest that the CCR5 phenotype is important in determining the
      replicative capacity of M-tropic HIV-1 in vitro. The implications of these
      results with relation to HIV-1 transmission and disease progression are
      discussed.

PMID- 10203037
TI  - Quantitation of antigen-specific CD8+ T-cell responses.
AB  - Enumeration of antigen-specific CD8+ T-cells has traditionally been largely
      dependent on the use of techniques that require a period of expansion in vitro.
      However the recent emergence of methods that can be used directly ex vivo to
      quantify antigen-specific CD8+ T cells has prompted a re-evaluation of the
      magnitude of viral-specific cellular immune responses. The purpose of this review
      is to describe the commonly used methods currently available to quantify and
      characterise antigen-specific T-cells and then to focus in more detail on the use
      of tetrameric complexes of HLA/peptide to study the cellular immune response.

PMID- 10203038
TI  - The role of HIV gp120 in the disruption of the immune system.
AB  - The existence of HIV positive individuals who do not appear to progress to
      disease, or do so only very slowly (LTNPs), strongly suggest that factors other
      than virus pathogenicity determine disease. The occurence of HIV infected
      chimpanzees that remain disease free and other African SIV infected primates
      where disease is apparently species specific underscores the importance of host
      factors [1,2]. We have examined the immune response of LTNP patients using a
      variety of techniques including intracellular cytokine FACscan, anchor PCR
      analysis of the T cell receptor and HLA typing of class II genes by DNA
      sequencing. Our results to date confirm that the development of disease is
      consistent with activation of a susceptible immune system, and that this could be
      due to the fact that HLA-like sequences of HIV may 'allo' activate the host
      immune response. In order to test this hypothesis further we have examined
      whether gp120 itself can bind and present specific peptides which may be capable
      of eliciting 'allo' activation responses in particular hosts.

PMID- 10203039
TI  - Characterization of HIV-1-specific T-helper cells in acute and chronic infection.
AB  - HIV-1 infection is associated with progressive and relentless destruction of the
      immune system in the majority of infected persons, but some persons appear to be
      able to successfully contain the virus in the absence of antiviral therapy. Such
      cases suggest that the host immune response can successfully contain the virus,
      and provide the rationale for concerted efforts to understand the host immune
      response to the virus and to develop new strategies to combat the infection with
      immune based therapies. Historically, the greatest hole in the immune repertoire
      in HIV-1 infection has been the lack of strong virus-specific proliferative
      responses. However, new studies have identified a potent Th cell response in some
      infected persons, and have shown a statistically significant negative correlation
      between plasma viremia and virus-specific CD4 T-helper cells directed at the p24
      protein. Moreover, early institution of potent antiviral therapy in the earliest
      stages of acute HIV-1 infection have led to persistent, strong HIV-1-specific T
      helper cell responses, analogous to those seen in persons who are able to control
      viremia in the absence of antiviral therapy. We hypothesize that this is because
      potent antiviral therapy is able to protect virus-specific Th cells as they
      become activated, and thus these cells are not lost in the earliest stages of
      infection.

PMID- 10203040
TI  - Apoptosis and the CD95 system in HIV disease: impact of highly active anti
      retroviral therapy (HAART).
AB  - Apoptosis markers and the rate of lymphocyte apoptosis were followed in the
      peripheral blood of HIV infected persons at various stages of disease. Our study
      suggests that the early increase in memory cells following therapy may also be
      due to a significant decrease in apoptosis in this subset. The intrinsic
      resistance to apoptosis in the naive subset appears to be maintained following
      HIV infection and is not modified following highly active anti-retroviral
      treatment (HAART).

PMID- 10203041
TI  - Detailed immunophenotype of CD8+ memory cytotoxic T-lymphocytes (CTL) against HIV
      1 with respect to expression of CD45RA/RO, CD62L and CD28 antigens.
AB  - We have previously reported that circulating effector cytotoxic CD8+ T
      lymphocytes (CTLs) against HIV-1 express CD38 and HLA-DR activation antigens. In
      this study, we performed two series of FACS sorts to phenotype and characterize
      precursors of CTL effectors. First we looked at memory CTL activity against HIV-1
      stimulated by antigen as well as CTL activity stimulated by CD3 mAb with regard
      to whether the precursors expressed CD45RA and/or CD62L. We found that the
      precursor cells that could be stimulated with antigen to become effectors within
      7 days predominated in the CD45RA CD62L subset. However. in donors with low
      levels of CD8+ T-cell activation as measured by CD38 antigen expression, memory
      cells could also be found in the CD45RA+ CD62L+ subset. Our data indicate that
      reversion of memory cells to the CD45RA+ CD62L+ phenotype can occur in humans,
      especially in donors with low levels of virus replication and minimal CD8 + T
      cell activation. Next, we looked at CD28 expression with regard to antigen
      specific memory cells and again found that the level of virus replication and
      CD8+ T-cell activation influenced the subset that contained the memory cells. In
      donors with high levels of virus replication, our results indicated that CTL were
      being actively recruited from both CD28+ and CD28 subsets, while in donors with
      undetectable levels of viral replication, the memory cells were entirely in the
      CD28 compartment.

PMID- 10203042
TI  - Subpopulations of peripheral blood dendritic cells show differential
      susceptibility to infection with a lymphotropic strain of HIV-1.
AB  - Blood dendritic cells (DC) express CD4 and are susceptible to HIV infection. By
      electron microscopy two morphologically distinct types of DC were identified in
      peripheral blood. Only one of these two types was susceptible to infection with a
      lymphotropic strain of HIV-1. By FACS two populations could be defined based on
      the expression of CD11c. The morphology of cultured FACS-purified CD11c negative
      DC was similar to that DC population shown to be susceptible to infection with
      the lymphotropic strain of HIV. Furthermore after several hours in culture CXCR4,
      the co-receptor for lymphotropic strains of HIV-1, was expressed at a
      significantly higher level on the CD11c negative DC than on the CD11c positive
      cells. This study suggests that there are subpopulations of DC that show
      differences in susceptibility to infection with some strains of HIV-1.

PMID- 10203043
TI  - Rational reconstitution of the immune repertoire in AIDS with autologous, antigen
      specific, in vitro-expanded CD4 lymphocytes.
AB  - HIV infection leads to decrease of CD4 lymphocytes. In particular, loss of CD4
      cells specific for opportunistic pathogens results in active opportunistic
      infections, that are the chief cause of morbidity and mortality in AIDS. Highly
      active anti-retroviral therapy (HAART) has been shown to have dramatic effects in
      a large fraction of treated individuals, such as decrease of viral load and
      increase of CD4 cells. It has not been clearly established, though, whether CD4
      cells that appear during HAART represent a functional repertoire (i.e. a CD4
      repertoire that encompasses all specificities, including T-cells responding to
      opportunistic pathogens, as in immunocompetent individuals) or an amplified
      mirror image of a defective repertoire. Therefore we propose that the immune
      repertoire can be reconstituted with autologous CD4 lymphocytes collected at
      early stages of infection, selected for specificity for opportunistic pathogens,
      expanded and stored for future use when laboratory or clinical signs indicate a
      depletion of antigen-specific CD4 cells. Since the reinfused CD4 cells are
      themselves susceptible to HIV infection-replication, we suggest that in vitro
      gene therapy of these cells may confer a genetic resistance that is permanently
      maintained in these cells.

PMID- 10203044
TI  - Dendritic cells generated from blood monocytes of HIV-1 patients are not infected
      and act as competent antigen presenting cells eliciting potent T-cell responses.
AB  - The CTL response to HIV-I can be vigorous, but antigen presenting cell
      requirements have not been studied in detail. To approach this question, we have
      examined the dendritic cell populations that can be obtained from the blood of
      HIV-1 infected individuals. We studied 13 asymptomatic patients, who spanned a
      wide range of plasma viremia and CD4 counts. We show here that sizeable numbers
      of mature dendritic cells can be generated from nonproliferating progenitors in
      the blood of HIV + patients using a recently developed approach. The procedure
      involves two steps. The first step or 'priming' phase is a 7 day culture of T
      cell depleted mononuclear cells in medium supplemented with GM-CSF and IL-4. The
      second step or 'differentiation' phase requires the exposure to monocyte
      conditioned medium. The yields of DCs from HIV + individuals were comparable to
      normal blood donors, 0.4 - 3 x 10(6) mature dendritic cells from 50 ml of blood.
      Strong APC function was evident for both the proliferation of allogeneic T-cells
      in the MLR, and the generation by syngeneic T-cells of class I restricted, CTL
      responses to influenza virus. A panel of dendritic cell restricted markers are
      expressed, including CD83, p55, and perinuclear CD68. By semi-quantitative PCR
      analysis, the cytokine derived cells did not express HIV-1 DNA. We suggest that
      these blood derived dendritic cells will be effective for studies of immune
      responses to HIV-1 antigens and may be considered as adjuvants for active
      immunotherapy.

PMID- 10203045
TI  - Antigen presenting cell function in HIV-1 infected patients.
AB  - Antigen presenting cell (APC) function is central to the activation of anti-viral
      cytotoxic T-cells and antibody production. In previous studies we have evaluated
      APC function in HIV-1 infected patients as the capacity to present peptide to a
      well defined panel of CD4 T-cell clones. We found that APC from HIV-1 infected
      patients were defective in the capacity to present peptide to CD4 T-cell clones.
      The APC defect uncovered by this method was present early in infection and
      worsened with increasing viral load, suggesting that it was an important
      determinant of progression and anti-viral efficacy. The CD4 T-cell clones were,
      however, found to vary in their susceptibility to the APC defect. CD4 T-cell
      clones that failed to respond to peptide presented by HIV + APC were 1000-fold
      more readily inhibited by anti-CD4 antibody than T-cell clones which consistently
      responded to APC from patients infected with HIV-1 (HIV + APC). An intermediate
      group of T-cell clones were also identified that only responded to peptide and
      HIV + APC from asymptomatic patients. These results suggested that the underlying
      mechanism for the APC defect was binding of T-cell CD4 by APC-associated gp120.
      In this paper we discuss the evidence to support this hypothesis.

PMID- 10203046
TI  - Comparison of restimulation methods to elicit SIV specific cytotoxic T
      lymphocytes (CTL) in vitro: Staphylococcal enterotoxin B (SEB) provides a novel
      method for the quantification of SIV specific CTL precursors.
AB  - Most investigators believe that an effective HIV-1 vaccine will have to induce
      high levels of HIV-1 specific cytotoxic T-cells (CTL). The macaque SIV
      challenge/protection model system has been used to test candidate vaccines, but
      quantitative immunogenicity measurements are difficult due to technical
      limitations of the assays available. The quantification of SIV specific CTLp is
      crucial to understanding correlates of immunity for these vaccines, but are
      difficult to measure. We have compared various methods to quantify SIV specific
      CTLp, and describe a novel method of SIV specific CTL in vitro stimulation using
      the superantigen Staphylococcal enterotoxin B (SEB). SEB can stimulate high
      levels of CTLp in vitro, and provides an alternative method to induce SIV
      specific CTL.

PMID- 10203047
TI  - Antibody neutralization of HIV-1 and the potential for vaccine design.
AB  - Neutralisation by antibody is, for a number of viruses, an in vitro correlate for
      protection in vivo. For HIV-1 this is controversial. However, the induction of a
      potent anti-HIV neutralising antibody response remains one of the principal goals
      in vaccine development. A greater knowledge of the fundamental mechanisms
      underlying the neutralisation process would help direct research towards suitable
      vaccine immunogens. The primary determinant of HIV neutralisation appears to be
      antibody affinity for the trimeric envelope glycoprotein spike on the virion,
      suggesting that epitope-specific effects are secondary and implying a single,
      dominant mechanism of neutralisation. Antibody interference with virion
      attachment to the target cell appears to be a major mechanism of neutralisation
      by gp120-specific antibodies. This is probably achieved both by antibody-induced
      dissociation of gp120 from gp41 and by direct inhibition of virus binding to
      receptor-coreceptor complexes. A gp41-specific antibody neutralises by
      interfering with post-attachment steps leading to virus membrane fusion. Recent
      advances in structural analyses of the HIV envelope glycoproteins coupled with
      data obtained from antibody mapping and neutralisation studies allow a greater
      understanding of Env function and its inhibition. This in turn should lead to a
      more rational basis for vaccine design aimed at stimulating highly effective
      neutralising antibodies.

PMID- 10203048
TI  - Suppression of human immunodeficiency virus type 1 replication by a soluble
      factor produced by CD8+ lymphocytes from HIV-2-infected baboons.
AB  - Human immunodeficiency virus type 2 (HIV-2)-infected baboons (Papio cynocephalus)
      provide a valuable animal model for the study of acquired immunodefidency
      syndrome (AIDS) pathogenesis since many features of disease progression resemble
      HIV-1-infection of humans. In some HIV-2-infected baboons that are clinically
      healthy, a CD8+ cell antiviral response, that is partly mediated by a soluble
      factor, controls viral replication in vitro. In the present study, we demonstrate
      that CD8+ cells derived from HIV-2-infected baboon peripheral blood, lymph nodes,
      adenoids and tonsils had antiviral activity in co-cultures of CD8+ and CD4+ cells
      that inversely correlates with viral load. A soluble factor was found to be
      active against the chemokine-resistant, syncytium-inducing HIV-1SF2 and HIV-1SF33
      isolates and was relatively heat stable at 100 degrees C for 10 min. Moreover,
      inhibition of the transcription from the long terminal repeat of HIV-1 was
      observed in 1G5 cells after activation with phorbol 12-myristate 13-acetate.
      Therefore, the soluble suppressing activity of CD8+ cells in HIV-2-infected
      baboons may be analogous to the CD8+ cell antiviral factor described in human HIV
      infected asymptomatic people.

PMID- 10203049
TI  - The implications of antigenic diversity for vaccine development.
AB  - The reactivity of human monoclonal and polyclonal anti-HIV-1 antibodies
      demonstrates that shared epitopes, including those that induce neutralizing
      antibodies, exist and are recognized by the human immune system. A priori, there
      is no reason why cross-clade neutralizing antibodies could not be induced by an
      appropriately constructed HIV vaccine. But to construct such a vaccine, it is
      critical to understand, as completely as possible, the antigenic structure of
      HIV, to establish and identify immunologic classifications for HIV, and to choose
      rationally the minimum number and types of viruses from these immunologic
      groupings that will induce the broadest protective responses.

PMID- 10203050
TI  - Live attenuated SIV--a model of a vaccine for AIDS.
AB  - The experimental infection of macaques with simian immunodeficiency virus (SIV)
      has provided strong evidence that it may be possible to develop a vaccine against
      AIDS. Live attenuated SIV vaccines have been found to confer the most potent
      protection against challenge with a variety of pathogenic viruses. This article
      summarizes the work performed at NIBSC to characterize the protection conferred
      by live attenuated SIV and to identify mechanisms of vaccine protection. The
      results of these experiments are discussed in conjunction with observations from
      related studies made by other groups.

PMID- 10203051
TI  - CD8-suppressor factor and beta-chemokine function as a complementary mechanism to
      cognate immunity.
AB  - Protection against SIV or HIV infection requires specific antibodies and T-cell
      immune responses. However, a complementary mechanism may be involved, in which
      CD8-suppressor factors (CD8-SF) and the constitutive beta-chemokines may prevent
      the virus binding and replicating. Indeed, there is evidence that targeted iliac
      lymph node (TILN) immunisation with SIVgp120 and p27 or xenoimmunisation with SIV
      grown in human T-cells generates CD8-SF, RANTES, MIP-1alpha and MIP-1beta which
      are significantly correlated with protection from SIV infection by the rectal
      mucosal or intravenous route, respectively. Inhibition of SIV replication in
      vitro is dependent on the concentration of beta-chemokines generated by
      immunisation. The critical level for inhibition of SIV replication appears to be
      higher for rectal mucosal than intravenous challenge by SIV. The mechanism of
      protection in vivo has not been elucidated but it is likely that the beta
      chemokines bind to CCR5 coreceptors which are internalised. Thus, CCR5
      coreceptors are either blocked or not expressed on the cell surface for SIV to
      bind and infect.

PMID- 10203052
TI  - Pre-clinical development of a multi-CTL epitope-based DNA prime MVA boost vaccine
      for AIDS.
AB  - Reliable and effective methods for induction of cytotoxic T-lymphocytes (CTL) are
      constantly persued. Central to this search is work in animal models, which allow
      to test novel vaccine strategies and ultimately lead to a more efficient planning
      of clinical trials. Here, human immunodeficiency virus (HIV) vaccine candidates
      were constructed as a string of partially overlapping CTL epitopes (20 human, 3
      macaque and 1 mouse) delivered and expressed using plasmid DNA and modified virus
      Ankara (MVA; an attenuated vaccinia virus), which are both vaccine vehicles
      acceptable for use in humans. In mice, these vaccines were shown to induce virus
      specific interferon-gamma-producing and cytolytic CD8+ T-cells after a single
      intramuscular needle injection. When immunization protocols were sought which
      would improve the level of induced HIV-specific T-cells, DNA priming-MVA boosting
      was found to be the most potent protocol. The multi-epitope DNA also elicited CTL
      when delivered intradermally using the Accell gene delivery device (gene gun).
      Finally, a combined intradermal gene gun DNA-MVA vaccination regimen induced in
      macaques high frequencies of circulating CTL, which were comparable to those
      observed in simian immunodeficiency virus (SIV)-infected monkeys. Further
      optimization of this method in non-human primates is under way. Thus, a
      vaccination regimen for an effective elicitation of CTL has been developed which
      might facilitate evaluation of the role(s) that these lymphocytes play in the
      control of SIV and HIV infections.

PMID- 10203053
TI  - Protection from pathogenic SIV challenge using multigenic DNA vaccines.
AB  - To assess DNA immunization as a strategy for protecting against HIV infection in
      humans, we utilized SIVmne infection of Macaca fascicularis as a vaccine
      challenge model with moderate pathogenic potential. We compared the efficacy of
      DNA immunization alone and in combination with subunit protein boosts. All of the
      structural and regulatory genes of SIVmne clone 8 were cloned into mammalian
      expression vectors under the control of the CMV IE-1 promoter. Eight M.
      fascicularis were immunized twice with 3 mg of plasmid DNA divided between two
      sites; intramuscular and intradermal. Four primed macaques received a further two
      DNA immunizations at weeks 16-36, while the second group of four were boosted
      with 250 microg recombinant gp160 plus 250 microg recombinant Gag-Pol particles
      formulated in MF-59 adjuvant. Half of the controls received four immunizations of
      vector DNA; half received two vector DNA and two adjuvant immunizations. As
      expected, humoral immune responses were stronger in the macaques receiving
      subunit boosts, but responses were sustained in both groups. Significant
      neutralizing antibody titers to SIVmne were detected in one of the subunit
      boosted animals and in none of the DNA-only animals prior to challenge. T-cell
      proliferative responses to gp160 and to Gag were detected in all immunized
      animals after three immunizations, and these responses increased after four
      immunizations. Cytokine profiles in PHA-stimulated PBMC taken on the day of
      challenge showed trends toward Thl responses in 2/4 macaques in the DNA
      vaccinated group and in 1/4 of the DNA plus subunit vaccinated macaques; Th2
      responses in 3/4 DNA plus subunit-immunized macaques; and Th0 responses in 4/4
      controls. In bulk CTL culture, SIV specific lysis was low or undetectable, even
      after four immunizations. However, stable SIV Gag-Pol- and env-specific T-cell
      clones (CD3+ CD8+) were isolated after only two DNA immunizations, and Gag-Pol-
      and Nef-specific CTL lines were isolated on the day of challenge. All animals
      were challenged at week 38 with SIVmne uncloned stock by the intrarectal route.
      Based on antibody anamnestic responses (western, ELISA, and neutralizing
      antibodies) and virus detection methods (co-culture of PBMC and LNMC, nested set
      PCR- of DNA from PBMC and LNMC, and plasma QC-PCR), there were major differences
      between the groups in the challenge outcome. Surprisingly, sustained low virus
      loads were observed only in the DNA group, suggesting that four immunizations
      with DNA only elicited more effective immune responses than two DNA primes
      combined with two protein boosts. Multigenic DNA vaccines such as these, bearing
      all structural and regulatory genes, show significant promise and may be a safe
      alternative to live-attenuated vaccines.

PMID- 10203054
TI  - HIV-1 vaccine-induced immune responses which correlate with protection from SHIV
      infection: compiled preclinical efficacy data from trials with ten different HIV
      1 vaccine candidates.
AB  - The specific immune mechanisms necessary and/or sufficient to elicit HIV-vaccine
      protection remain undefined. Utilising the SHIV rhesus macaque model the
      immunogenicity as well as the efficacy of ten different HIV-1 vaccine candidates
      was evaluated. Comparison of the immune responses induced, with the ability of
      the vaccine to protect from SHIV infection provided a means to determine which
      type of immune responses were necessary for protection. Vaccine candidates
      included VLPs, DNA, subunit protein with novel adjuvant formulations, ISCOMs and
      pox-virus vectors. Protection from SHIV infection was achieved in approximately
      half of the animals which received a primary intravenous cell-free challenge. The
      presence of CTL in the absence of other effector responses did not correlate with
      protection from this route and type of challenge. Virus neutralising antibodies
      (Nab) appeared to be necessary but alone were insufficient for protection. If Ag
      specific IFN-gamma and/or IL-4 as well as lymphoproliferative (LP) responses were
      found with the lack of a detectable IL-2 response, then protection was not
      observed. Immunity correlated with the magnitude of Nab responses, beta
      chemokines and as well as balanced, qualitative T-helper responses.

PMID- 10203055
TI  - 'Naive' and 'memory' CD4+ T-cells and T-cell receptor (TCR) V beta repertoire
      dynamics are independent of the levels of viremia following HIV seroconversion.
AB  - The progression of 'naive' and 'memory' T-cells and the T-cell receptor Vbeta
      (TCR Vbeta) repertoire dynamics within the peripheral CD4+ T-cell compartment
      were studied in individuals following HIV seroconversion. Profound TCR Vbeta
      repertoire perturbations were observed within the CD4+ T-cell pool in treatment
      naive patients regardless of their levels of viremia during the first 6-8 months
      after seroconversion. The ratio of 'naive' to 'memory' CD4+ T-cells as well as
      the TCR Vbeta repertoire dynamics did not appear to correlate with absolute
      numbers of CD4 T-cells.

PMID- 10203056
TI  - Restoration of the immune system with anti-retroviral therapy.
AB  - Clinical benefits of highly active anti-retroviral treatments (HAART) are
      increasingly evidenced by resolving opportunistic infections and malignancies, as
      well as declining hospitalization and mortality rates [1]. This suggests that
      potent and sustained suppression of viral replication, at least to some extent,
      is associated with reconstitution of the immune system even in adult patients
      treated at advanced stages of the disease. Increased susceptibility to
      opportunistic infections and tumors mainly results from the loss of memory CD4+ T
      cell reactivity against recall antigens which is an early event in HIV disease
      progression. Primary responses of naive CD4+ T cells against new pathogens are
      suppressed even earlier in the course of HIV disease, and the progressive
      depletion in naive CD4+ T cells reflects profound alterations in T cell
      regeneration capacities. Previous studies revealed that monotherapy with
      ritonavir, a protease inhibitor, resulted in a slight improvement in memory CD4+
      T cell responses to recall Ags only when detectable prior to onset of therapy,
      suggesting that the loss of CD4+ T cell reactivity might be irreversible at
      advanced stages of the disease [2]. In contrast our group demonstrated more
      recently that restoration in CD4+ T cell reactivity to specific antigens was
      feasible when HAART was administered in progressors [3]. Here we address some of
      the questions raised by immune restoration with HAART when administered at
      advanced stages of the disease.

PMID- 10203057
TI  - Antigen-specific T-lymphocyte proliferative responses during highly active
      antiretroviral therapy (HAART) of HIV-1 infection.
AB  - To evaluate functional T-cell recovery during combination therapy with ritonavir,
      lamivudine (3TC), and zidovudine (ZDV), peripheral blood mononuclear cells (PBMC)
      were obtained from 4 HIV-1 infected patients (baseline values: 40 403 CD4+ T
      cells/microl; 4.6-6.4 log HIV-1 RNA copies/ml) before HAART administration (week 
      1) and after 5, 20, and 37 weeks of treatment on average. In vitro
      lymphoproliferative responses (LPR) to C. albicans, tetanus toxoid, and M.
      tuberculosis protein purified derivative (PPD), as recall antigens (Ag), and to
      recombinant HIV-1 Gag-p24 and p17 were measured by 3H-Thymidine incorporation.
      LPR to recall Ag, almost undetectable before therapy, appeared in all four
      patients during HAART soon after maximal load reduction was achieved. LPR to Gag
      p17, but not to p24, became also detectable in three patients, even though
      remaining weak. In conclusion, improved T-lymphocyte function during HAART was
      achieved probably mostly as a result of lower virus inhibitory factors and
      cytokines.

PMID- 10203058
TI  - Molecular tracking of an Human Immunodeficiency Virus nef specific cytotoxic T
      cell clone shows persistence of clone-specific T-cell receptor DNA but not mRNA
      following early combination antiretroviral therapy.
AB  - The mechanisms that lead to maintenance of an active effector cytotoxic T-cell
      (CTL) response in Human Immunodeficiency Virus type-1 (HIV-1) infection are not
      well understood. We have investigated the role of antigen in maintenance of an
      HIV-1 specific CTL response by studying a patient (313-7) whose antigenic
      stimulus was reduced using antiretroviral drug therapy started within 90 days of
      HIV-1 infection. This patient made a primary monospecific CTL response to an HLA
      C*0802 restricted epitope in nef (KAAVDLSHFL) prior to treatment. Within 7 days
      of starting treatment the nef specific CTL precursor frequency (CTLp) had
      decreased from 60/10(6) to 4/10(6) peripheral blood mononuclear cells (PBMC),
      coincident with a decline in viremia from 18 470 to 615 copies/ml. Both plasma
      viremia and nef specific CTLp remained at low levels for 180 days. The nef
      specific CTL clone T-cell receptor (TCR) mRNA transcripts also decreased after
      treatment, but clone specific TCR DNA persisted. It appears that removal of
      antigen alters the state of HIV specific CTL from an activated effector
      population (detected in the CTLp assay and by measurement of clone specific RNA)
      to a non-activated quiescent population (detected by measurement of clone
      specific DNA). This latter population may represent persisting HIV specific
      memory CTL.

PMID- 10203059
TI  - Humanisation and characterisation of PR1A3, a monoclonal antibody specific for
      cell-bound carcinoembryonic antigen.
AB  - Carcinoembryonic antigen (CEA) is highly expressed by most tumours of
      gastrointestinal origin, but its use as a target for tumour therapy is
      complicated by the high levels of soluble CEA that are found circulating in the
      blood of cancer patients. A monoclonal antibody PR1A3 has been prepared, which
      binds preferentially to cell-surface rather than soluble CEA, this cell
      selectivity should make PR1A3 an ideal candidate for antibody-targeted tumour
      therapy. PR1A3 has been humanised and shown to retain its cell-surface
      specificity and affinity. Stable expression of the humanised antibody from
      chinese hamster ovary (CHO) cells has been achieved after transfection and
      amplification. Since PR1A3 binds preferentially to cell-associated CEA, a cell
      free enzyme-linked immunosorbent assay (ELISA) has been developed to allow
      characterisation and routine assay of the antibody. This assay was developed
      using a recombinant chimeric protein constructed by cloning the domain of CEA
      that is bound by PR1A3 (the B3 domain) into a hybrid gene containing the Fc
      portion of IgG and three domains of biliary glycoprotein. Stable expression of
      this hybrid protein has been achieved from CHO cells. In ELISA both humanised and
      murine PR1A3 bound strongly to this antigen but only at a minimal level to
      soluble CEA. Two binding sites for the antibody were found on the gastric
      carcinoma cell line MKN45, one of higher affinity (1 nM) and the other at lower
      affinity (60 nM). Similar affinities were found for both murine and humanised
      antibodies. The data presented make it unlikely that the differential binding to
      cell-surface as distinct from soluble CEA can be accounted for by low affinity of
      PR1A3 for CEA, and provides further support for the hypothesis that some
      conformational change takes place on CEA release from cells and that it is this
      change that blocks PR1A3 binding to its epitope.

PMID- 10203060
TI  - Effect of local interleukin-2 treatment on spontaneous tumours of different
      immunogenic strength.
AB  - Transplantable tumour lines established from spontaneous tumours of BALB/c, CBA,
      and DBA/2 mice displayed different immunogenic strength. This report describes
      tumour susceptibility to interleukin-2 (IL-2) therapy in relation to tumour
      immunogenicity. The following tumour lines were used: X5, X6, and X9 mammary
      tumours of DBA/2, BALB/c, and CBA origin respectively, X7 carcinoma of BALB/c and
      X18 papilloma of CBA mice. Two spontaneous tumours of long transplantation
      history, SL2 lymphoma (SL2) of DBA/2 and Madison lung carcinoma M109 (M109) of
      BALB/c origin, were used as control systems. Experimental mice were transplanted
      with different inocula of tumour cells at day 0; treatment with IL-2 was
      initiated on days 1-3 or delayed until day 10 and consisted of daily injections
      of low doses of 5000 or 20,000 U/mouse given five times a week for a period of 3
      weeks. Treatment of SL2 (2 x 10(4) cells injected i.p.) consisted of i.p.
      injections of 5000 or 20,000 U IL-2/mouse given on days 10-14 after tumour
      transplantation. IL-2 therapy of SL2-bearing DBA/2JIco mice resulted in a
      significant proportion of cures; however, no response to IL-2 treatment was
      achieved in SL2-bearing DBA/2CrIiw mice. BALB/c mice with the i.p. transplant of
      M109 responded to IL-2 treatment with 40% increase in lifespan. The low-dose IL-2
      therapy of the five spontaneous tumours resulted, in general, in transient growth
      inhibition of the i.m. transplants of lines X5, X6, and X7 provided that IL-2 was
      administered locally. The therapeutic effect depended on the number of
      transplanted tumour cells, the best results being achieved at cell numbers close
      to the dose-inducing tumour growth in 50% of animals. We found that the
      spontaneously arising tumours responding to IL-2 treatment were all slowly
      growing and immunogenic (X6 and X7) or might have viral association (X5) and, as
      such, might express foreign antigens. The data suggest a correlation between
      tumour immunogenicity and the therapeutic effect. However, IL-2 can still exert
      some effect against tumours with negligible immunogenicity.

PMID- 10203061
TI  - Autoantibodies against the tumour-associated antigen GA733-2 in patients with
      colorectal carcinoma.
AB  - The tumour-associated antigen (TAA) GA733-2 is expressed as a non-secreted
      surface molecule on the majority of human colorectal carcinoma cells. The antigen
      has been used as a target for passive and active immunotherapy during the last
      decade. To determine the incidence of autoantibodies against this antigen, sera
      from 1068 patients with colorectal carcinoma were analysed for naturally
      occurring IgG antibodies against the baculovirus-produced GA733-2E protein. A
      total of 14.5% of the patients had IgG antibodies against the antigen. In 519
      patients, sera were collected at the time of diagnosis and 15% of those patients
      had anti-GA733-2E IgG antibodies. There was a tendency to a higher frequency of
      patients with antibodies among those in the advanced Dukes stages: 11% in stage A
      and 32% in stage D respectively (P = 0.06). Antibodies could be detected for up
      to 10 years after the diagnosis. Patients with Crohn's disease or colitis
      ulcerosa (n = 20) did not elicit anti-GA733-2E antibodies. No healthy control
      donor (n = 45) had detectable antibodies against the antigen. The specificity of
      GA733-2E-reactive serum IgG was indicated by significant inhibition of mAb17-1A
      (originally used to define GA733-2) binding to the GA733-2E antigen. Sera of
      positive patients bound to the GA733-2-expressing human colorectal carcinoma cell
      line, SW948. No significant correlation was found between the presence of
      antibodies and survival in the present patient population. However, the high
      incidence of autoantibodies against this tumour antigen in colorectal carcinoma
      patients confirms its antigenicity in humans and supports the use of the GA733-2
      antigen as a target for immunotherapy.

PMID- 10203062
TI  - Kinetics of cellular trafficking and cytotoxicity of 9.2.27-gelonin immunotoxins
      targeted against the high-molecular-weight melanoma-associated antigen.
AB  - The high-molecular-weight melanoma-associated antigen (HMW-MAA) is expressed on a
      large majority of melanoma tissues but not on most normal or other neoplastic
      tissues. Monoclonal antibody 9.2.27 binds with high affinity and specificity to
      the HMW-MAA, making it an attractive choice as an agent for targeting toxins or
      chemotherapeutic agents specifically towards melanomas. To characterize the
      interactions between 9.2.27 and melanoma cells more carefully, data on the
      kinetics of binding, internalization, and degradation of 9.2.27 by SK-MEL-2 cells
      were collected. Binding of 9.2.27 to SK-MEL-2 cells was rapid, and followed by
      slow loss of surface-bound antibody, probably because of loss of surface antigen
      caused by degradation and/or shedding. A small fraction (approx. 5%) of surface
      bound 9.2.27 was internalized and degraded. A mathematical model describing these
      interactions was developed, and equilibrium and kinetic constants were fitted to
      the data. To evaluate the utility of 9.2.27 as a toxin-targeting agent, 9.2.27
      gelonin immunotoxins were constructed and tested in protein synthesis inhibition
      assays. The dependence of the toxicity data for 9.2.27-gelonin on time and
      concentration was quantitatively related to the accumulated intracellular
      exposure to 9.2.27-gelonin by a relatively simple equation. This equation had
      been previously validated for immunotoxins targeted against the transferrin
      receptor, for which the trafficking kinetics are quite dissimilar from those of
      the HMW-MAA. The success of the approach here suggests that this method may be
      widely applicable for analysis of immunotoxin efficacy.

PMID- 10203063
TI  - Rejection of tumors of the B cell lineage by idiotype-vaccinated mice.
AB  - Idiotypic determinants of immunoglobulins of malignant B lymphocytes and plasma
      cells are tumor-specific antigens and have been used extensively in immunotherapy
      studies. The mechanisms involved in resistance to tumor challenge following
      idiotype vaccination are poorly understood. Although a predominant role has been
      attributed to anti-idiotype antibodies, both humoral and cellular immune
      responses are probably involved. Cell-mediated responses may be particularly
      effective against tumor cell variants that do not express the idiotype on the
      cell surface and are therefore resistant to anti-idiotype antibodies but continue
      to produce one of the original immunoglobulin polypeptides that may be processed
      and presented to T cells. In this report we describe two experimental models of
      idiotype vaccination in which antibodies are unlikely to play a role, and hence
      tumor immunity is attributed to cell-mediated responses. One model consists of
      the murine B lymphocyte tumor 38C-13 and its idiotype-negative variant DB2, which
      has lost the idiotypic specificity of the parental 38C-13 cell line through the
      production of a different light chain but expresses the original heavy chain.
      Vaccination of mice with the purified IgM of 38C-13 induced resistance to 38C-13
      tumor cells as well as to the variant cells. Although immunized mice produced
      high levels of anti-idiotype antibodies that bound to 38C-13 cells, no binding of
      antibodies to DB2 cells occurred. The finding that idiotype-vaccinated mice were
      resistant to idiotype-negative DB2 cells suggested that cellular mechanisms are
      involved in mediating resistance. The second model consists of the two plasma
      cell line JLmu s and JLmu m, which produce IgM with an identical specificity.
      Whereas one of them (JLmu s) secretes the IgM, the other one (JLmu m) can neither
      secrete nor deposit it on the cell surface. Immunization against JLmu s IgM
      followed by tumor challenge resulted in prolonged survival of both JLmu s- and
      JLmu m-challenged mice. Although sera of immunized mice contained high levels of
      anti-idiotype antibodies, they did not react with the plasmacytoma cells.
      Similarly to the results obtained in the 38C-13 experimental model, these results
      suggest that a non-antibody-mediated mechanism was involved in the resistance of
      mice to tumor growth.

PMID- 10203064
TI  - Vaccination with the extracellular domain of p185neu prevents mammary tumor
      development in neu transgenic mice.
AB  - The HER2/neu oncogene product, p185(HER2/neu), is overexpressed on the surface of
      many human breast cancers. Strains of transgenic mice have been developed that
      express the rat neu oncogene in mammary epithelial cells and develop spontaneous
      mammary tumors that overexpress p185neu. This model provides an ideal system for
      testing interventions to prevent tumor development. In this study, we immunized
      neu-transgenic mice with a vaccine consisting of the extracellular domain of
      p185neu (NeuECD). Immunized mice developed Neu-specific humoral immune responses,
      as measured by circulating anti-Neu antibodies in their sera, and cellular immune
      responses, as measured by lymphocyte proliferation to NeuECD in vitro. In
      addition, the subsequent development of mammary tumors was significantly lower in
      immunized mice than in controls and vaccine treatment was associated with a
      significant increase in median survival.

PMID- 10203066
TI  - Cancer Vaccine Week, an international symposium 5-9 October 1998, New York, NY.

PMID- 10203065
TI  - Comparison of simian virus 40 large T antigen recombinant protein and DNA
      immunization in the induction of protective immunity from experimental pulmonary
      metastasis.
AB  - In this report we examine the ability of a recombinant tumor antigen preparation
      to prevent the establishment of experimental pulmonary metastasis. Baculovirus
      derived recombinant simian virus 40 (SV40) large tumor antigen (T-Ag) was
      injected into BALB/c mice followed by challenge with an intravenous injection of
      syngeneic SV40-transformed tumorigenic cells. The experimental murine pulmonary
      metastasis model allows for the accurate measurement of metastatic lessions in
      the lungs at various times after the challenge, using computer-assisted video
      image analysis. Following challenge, lung metastasis and survival data for the
      groups of mice were obtained. Animals immunized with recombinant SV40 T-Ag showed
      no detectable sign of lung metastasis and survived for more than 120 days after
      challenge. Antibodies specific for SV40 T-Ag were detected in the serum of
      immunized mice by enzyme-linked immunosorbent assay. Splenocytes obtained from
      mice immunized with recombinant SV40 T-Ag did not lyse syngeneic tumor cells,
      indicating that no cytotoxic T lymphocyte response was induced. Control mice
      developed extensive lung metastasis and succumbed to lethal tumor within 4 weeks
      after challenge. These data indicate that immunization with the recombinant SV40
      T-Ag induces protective, T-Ag-specific immunity in an experimental pulmonary
      tumor metastasis model.

PMID- 10203067
TI  - Twenty years of the Journal of Homosexuality: a bibliometric examination of the
      first 24 volumes, 1974-1993.
AB  - This study examines and evaluates the contents of the first 24 volumes of Journal
      of Homosexuality (JH), from 1974 to 1993. Data from each issue of JH, in terms of
      source articles and contributing authors, were collected and analyzed. JH is
      shown to be a scholarly journal, with high rates of citations per article, high
      levels of author education, a prevalence of scholarly methodological approaches,
      and a low rate of self-citation. Articles that disseminated the findings of
      empirical research noticeably decreased over time, while articles focusing on
      historical analysis noticeably increased. This trend was consonant with the
      change over time of JH's mission statement and editorial policy.

PMID- 10203068
TI  - Homosexuality and the human genome project: private and public choices.
AB  - Recent scientific research which offers evidence of genetic and biologic
      influence in homosexuality has created serious concerns. The intent of this
      article is to offer suggestions based in principles of bioethics in which
      perceived negative outcomes may be diminished and the positive qualities of the
      research enhanced. For a portion of the general population the concerns expressed
      in this article could be alleviated through public discussion and exposure to the
      findings and theories of the academic and scientific communities. For another
      portion of the population, however, additional safeguards against misuse of
      screening tests and somatic cell interventions may be advisable through efforts
      initiated by researchers themselves, general public policies, and additional
      medical policies. While these efforts are recommended as short term goals for the
      separate scientific and social paradigms of homosexuality, it is proposed that an
      equally important and related debate involves the subjects of disease, normality
      and the value of diversity. It is suggested that while it is imperative that the
      behavioral and biological sciences recognize the limitations of their separate
      approaches, the reductionist approach itself limits our understanding of what
      essentially are questions of attraction and relationships. In conclusion,
      homosexuality should be understood from the perspective of autonomy as every
      person's right to experience a full and meaningful life.

PMID- 10203069
TI  - Medical student homophobia.
AB  - OBJECTIVE: To determine whether homophobia existed in a sample of the second-year
      medical school class before beginning a course on Human Sexuality. METHOD: We
      administered a questionnaire to a sample of the second-year class at an
      introductory lecture to the course on Human Sexuality. This questionnaire asked
      twelve questions regarding attitudes about homosexuality, and incorporated
      questions from other surveys used previously. RESULTS: The data indicated
      significant homophobia. One-quarter of the students reported believing
      homosexuality is immoral and dangerous to the institution of the family, and
      expressed aversion to socializing with homosexuals. Nine percent believed
      homosexuality to be a mental disorder and 14% felt more homophobia since AIDS.
      CONCLUSIONS: Medical student homophobia, if left unchallenged, will hinder care
      provided to homosexual patients. Physician homophobia may disallow a healthy
      doctor-patient relationship and may cause a decrease in patients' ability to
      disclose sensitive issues.

PMID- 10203070
TI  - Heteronegativism? The attitudes of gay men and lesbians toward heterosexuals.
AB  - Although many studies have been conducted on homophobia, little information
      exists about the attitudes of homosexuals toward heterosexuals. In order to
      compare the attitudes of both groups, a well-known homophobia questionnaire
      (Hudson & Ricketts, 1980) was reworded to assess the attitudes of homosexuals
      toward heterosexuals, forming a "heterophobia" questionnaire. The less clinical
      term "heteronegativism" is introduced here to refer to the range of negative
      feelings that gay individuals could possess regarding heterosexuals. Sixty
      homosexual students were matched with 60 heterosexual psychology students on sex,
      age, race, and education. Each group was given its respective "phobia"
      questionnaire. Hypotheses that homosexual participants would report less phobia
      and more negative experience than heterosexuals and that gay women would report
      more phobia than gay men were supported. Hypotheses that level of abuse in
      closeted homosexuals would be positively correlated with phobia scores and that
      being "out of the closet" would be negatively correlated with phobia scores were
      not supported.

PMID- 10203071
TI  - Gay male, lesbian and bisexual health-related research funded by the National
      Institutes of Health between 1974 and 1992.
AB  - Health-related problems among lesbians, bisexuals, and gay men require research
      before solutions to them can be identified. This paper describes NIH sponsored
      research listing homosexuality as a primary or secondary issue between 1974 and
      1992. Homosexual projects unrelated to HIV and excluding capitol funding averaged
      only $532,000 per year compared to about $20 million per year since 1982 for HIV
      projects. Considering the range of health threats to these communities and the
      amounts needed to deal with HIV alone, current funding is clearly inadequate.
      Community members, scientists, experts, and others need to take action if
      appropriate research is to be done and the health needs of these groups are to be
      addressed.

PMID- 10203072
TI  - Gay, lesbian, and bisexual youth and young adults: social support in their own
      words.
AB  - Perceived social support was explored in a qualitative study of 17 gay, lesbian,
      and bisexual youth and young adults from a Seattle-based sexual minority youth
      drop-in center. The participants were interviewed in person with an open-ended
      question format to describe, in their own words, perceived social support they
      received as sexual minorities. Support was organized into four types, those
      fulfilling concrete, emotional, financial, or informational needs. Content
      analysis revealed several themes of support tailored to the specialized needs
      participants had as sexual minorities: locating parental figures among other gays
      and lesbians, parental reactions to learning of the youths' sexual orientation,
      the ability to reciprocate support, and finding supporters who introduced the
      youth to the gay, lesbian, and bisexual community. Non-family members were found
      to be more supportive than family members, particularly regarding informational
      support. Sexual minorities were perceived as more supportive than non-sexual
      minorities. Understanding the process and significance of acquiring a sense of
      community from which youth may garner continued support may present an avenue for
      intervention among social service providers. Additional implications for practice
      and research are also discussed.

PMID- 10203073
TI  - Integration within a transgender social network and its effect upon members'
      social and political activity.
AB  - The purpose of this study is to examine the male to female transgender social
      networks and how they influence social and political activity. Four Transgender
      organizations within Northeast Ohio were contacted for this study. Members were
      asked to complete a questionnaire and to mail it back. Few of the network
      elements were useful in predicting social and political activity. Network size
      has a positive effect upon a person's social and political activity, as did
      meeting attendance. This study suggests the importance of social networks for
      Trans-people.

PMID- 10203074
TI  - The "we of me": Carson McCullers as lesbian novelist.
AB  - Although Carson McCullers camouflaged her love for women in her fiction, gay and
      lesbian themes are inarguably present in her work. The loneliness that her
      characters face takes on allegorical intensity, and it is even more potent due to
      her own sexual confusion and alienation. Married twice to the same man and
      falling in love repeatedly with both women and men, McCullers wrestled with
      bisexuality throughout her personal and literary life. Her deepest attachments
      were to her husband Reeves McCullers; David Diamond, a musician-composer in love
      with both McCullers and her husband; and Anne-marie Clarac-Schwarzenbach, a Swiss
      writer. All three of these love interests required that McCullers deal with
      complicated and ultimately destructive triangles. Given that fact, it is no
      surprise that she created fictional worlds peopled with characters engaged in
      three-way relationships. In her novels, Mick (The Heart Is a Lonely Hunter),
      Frankie (The Member of the Wedding), Miss Amelia (The Ballad of the Sad Cafe) and
      Weldon Penderton (Reflections in a Golden Eye) also reflect the author's sexual
      ambivalence and inability to fit into the prescribed social structures of the
      South.

PMID- 10203076
TI  - Risk factors for intraoperative injury during cholecystectomy: an ounce of
      prevention is worth a pound of cure.

PMID- 10203075
TI  - Complications of cholecystectomy: risks of the laparoscopic approach and
      protective effects of operative cholangiography: a population-based study.
AB  - BACKGROUND: Previous studies suggest that laparoscopic cholecystectomy (LC) is
      associated with an increased risk of intraoperative injury involving the bile
      ducts, bowel, and vascular structures compared with open cholecystectomy (OC).
      Population-based studies are required to estimate the magnitude of the increased
      risk, to determine whether this is changing over time, and to identify ways by
      which this might be reduced. METHODS: Suspected cases of intraoperative injury
      associated with cholecystectomy in Western Australia in the period 1988 to 1994
      were identified from routinely collected hospital statistical records and lists
      of persons undergoing postoperative endoscopic retrograde
      cholangiopancreatography. The case records of suspect cases were reviewed to
      confirm the nature and site of injury. Ordinal logistic regression was used to
      estimate the risk of injury associated with LC compared with OC after adjusting
      for confounding factors. RESULTS: After the introduction of LC in 1991, the
      proportion of all cholecystectomy cases with intraoperative injury increased from
      0.67% in 1988-90 to 1.33% in 1993-94. Similar relative increases were observed in
      bile duct injuries, major bile leaks, and other injuries to bowel or vascular
      structures. Increases in intraoperative injury were observed in both LC and OC.
      After adjustment for age, gender, hospital type, severity of disease,
      intraoperative cholangiography, and calendar period, the odds ratio for
      intraoperative injury in LC compared with OC was 1.79. Operative cholangiography
      significantly reduced the risk of injury. CONCLUSION: Operative cholangiography
      has a protective effect for complications of cholecystectomy. Compared with OC,
      LC carries a nearly twofold higher risk of major bile, vascular, and bowel
      complications. Further study is required to determine the extent to which
      potentially preventable factors contribute to this risk.

PMID- 10203077
TI  - Laparoscopic management of benign solid and cystic lesions of the liver.
AB  - OBJECTIVE: The authors present their experience in the laparoscopic management of
      benign liver disease. The aim of the study is to analyze technical feasibility
      and evaluate immediate and long-term outcome. SUMMARY BACKGROUND DATA:
      Indications for the laparoscopic management of varied abdominal conditions have
      evolved. Although the minimally invasive treatment of liver cysts has been
      reported, the laparoscopic approach to other liver lesions remains undefined.
      METHODS: Between September 1990 and October 1997, 43 patients underwent
      laparoscopic liver surgery. There were two groups of benign lesions: cysts (n =
      31) and solid tumors (n = 12). Indications were solitary giant liver cysts (n =
      16), polycystic liver disease (n = 9), hydatid cyst (n = 6), focal nodular
      hyperplasia (n = 3), and adenoma (n = 9). Only solid tumors, hydatid cysts, and
      patients with polycystic disease and large dominant cysts located in anterior
      liver segments were included. All giant solitary liver cysts were considered for
      laparoscopy. Patients with cholangitis, cirrhosis, and significant cardiac
      disease were excluded. Data were collected prospectively. RESULTS: The procedures
      were completed laparoscopically in 40 patients. Median size was 4 cm for solid
      nodules and 14 cm for solitary liver cysts. Conversion occurred in three patients
      (7%), for bleeding (n = 2) and impingement of a solid tumor on the inferior vena
      cava (n = 1). The median operative time was 179 minutes. All solitary liver cysts
      were fenestrated in less than 1 hour. There were no deaths. Complications
      occurred in 6 cases (14.1%). Two hemorrhagic and two infectious complications
      were noted after management of hydatid cysts. There were no complications after
      resection of solid tumors. Three patients received transfusions (7%). The median
      length of stay was 4.7 days. Median follow-up was 30 months. There was no
      recurrence of solitary liver or hydatid cysts. One patient with polycystic
      disease had symptomatic recurrent cysts at 6 months requiring laparotomy.
      CONCLUSION: Laparoscopic liver surgery can be accomplished safely in selected
      patients with small benign solid tumors located in the anterior liver segments
      and giant solitary cysts. The laparoscopic management of polycystic liver disease
      should be reserved for patients with a limited number of large, anteriorly
      located cysts. Hydatid disease is best treated through an open approach.

PMID- 10203078
TI  - Enteral nutritional supplementation with key nutrients in patients with critical
      illness and cancer: a meta-analysis of randomized controlled clinical trials.
AB  - OBJECTIVE: To conduct a meta-analysis of 11 randomized controlled trials
      comparing enteral nutritional support supplemented with key nutrients versus
      standard enteral nutritional support to determine effects on morbidity and
      mortality rates and hospital stay. BACKGROUND DATA: Recent studies have shown
      that malnutrition occurs in up to 30% of patients undergoing gastrointestinal
      surgery, resulting in an increased risk of postoperative complications and death.
      With the realization that key nutrients can modulate inflammatory, metabolic, and
      immune processes, enteral nutritional regimens (supplemented with large amounts
      of key nutrients) have been developed for clinical use. METHODS: Eleven
      prospective, randomized controlled trials evaluating 1009 patients treated with
      combinations of key nutrients (Impact, Immun-Aid) were evaluated. Outcome
      measures examined were the incidences of pneumonia, infectious complications, and
      death, and length of hospital stay. Meta-analyses were undertaken to obtain the
      odds ratio and 95% confidence interval for incidences of infectious
      complications, pneumonia, and death, and the weighted mean difference and 95%
      confidence interval for length of hospital stay. RESULTS: The provision of
      nutritional support supplemented with key nutrients to patients with critical
      illness resulted in a decrease in infectious complications when compared with
      patients receiving standard nutritional support and a significant reduction in
      overall hospital stay. Similar results were documented in patients with
      gastrointestinal cancer. However, there were no differences between patient
      groups for either pneumonia or death. CONCLUSIONS: This meta-analysis has
      demonstrated that nutritional support supplemented with key nutrients results in
      a significant reduction in the risk of developing infectious complications and
      reduces the overall hospital stay in patients with critical illness and in
      patients with gastrointestinal cancer. However, there is no effect on death.
      These data have important implications for the management of such patients.

PMID- 10203080
TI  - Laparoscopic resection does not adversely affect early survival curves in
      patients undergoing surgery for colorectal adenocarcinoma.
AB  - OBJECTIVE: To determine the survival curves for laparoscopic resection (LR) of
      colorectal cancer. SUMMARY BACKGROUND DATA: Laparoscopic resection for cure of
      colorectal cancer is controversial, and survival curves have not been determined.
      METHODS: A prospective database of 177 consecutive LRs of colorectal cancers
      performed between November 1991 and 1997 was reviewed. The TNM classification
      (stage 0, I, II, III, and IV) for colorectal cancers and the Kaplan-Meier method
      were used to determine survival curves. RESULTS: Of the 177 patients, 5 were
      excluded for not having adenocarcinomas. Twenty-five patients (14.5%) had
      conversion to open surgery; most of these patients had rectal cancer or tumor
      invasion to adjacent organs. Twelve patients were lost to follow-up. All 135
      remaining patients had follow-up. Overall, 28 deaths occurred during the follow
      up period, 15 of which were cancer-related. The median follow-up was 24 months
      for patients with stage I, II, and III disease and 9 months for patients with
      stage IV disease. Observed 2-year survival rates were 100% stage I, 88.7% stage
      II, 80.6% stage III, and 28.6% stage IV. Survival rates at 4 years were 100%
      stage I, 79.5% stage II, 53.7% stage III, and 0% stage IV. No trocar site
      recurrence was observed. CONCLUSIONS: Early survival curves for patients with
      colorectal cancer who underwent LR do not differ negatively from historical
      controls for conventional surgery. Further validation is needed.

PMID- 10203079
TI  - Intestinal cytokine response after gut ischemia: role of gut barrier failure.
AB  - OBJECTIVE: To investigate the effect of intestinal ischemia with and without a
      reperfusion injury on intestinal cytokine production and gut permeability.
      SUMMARY BACKGROUND DATA: In humans and in animal models, the gut has been
      implicated as a cytokine-producing organ after ischemia/reperfusion (I/R)-type
      injuries. Because of the limitations of in vivo models, it has been difficult to
      demonstrate directly that the gut releases cytokines after an I/R injury or
      whether there is a relation between the magnitude of the ischemic process and the
      cytokine response. METHODS: Ileal mucosal membranes from rats subjected to sham
      or 45 or 75 min of superior mesenteric occlusion (SMAO) or 45 minutes of SMAO and
      30 minutes of reperfusion (SMAO 45/30) were mounted in the Ussing chamber system.
      Levels of tumor necrosis factor-alpha and interleukin-6 were serially measured in
      the mucosal and serosal reservoirs of the Ussing system, as was mucosal
      permeability as reflected by the passage of bacteria or phenol red across the
      ileal membrane. In a second group of experiments, Escherichia coli C25 was added
      to the mucosal reservoir to determine if the cytokine response would be
      increased. RESULTS: Mucosal and serosal levels of tumor necrosis factor-alpha
      were equally increased after SMAO, with the highest levels in the 75-minute SMAO
      group. The highest levels of interleukin-6 were found in rats subjected to 75
      minutes of SMAO or SMAO 45/30; the serosal levels of interleukin-6 were four to
      sixfold higher than the mucosal levels. The addition of E. coli C25 resulted in a
      significant increase in the amount of interleukin-6 or tumor necrosis factor
      alpha recovered from the mucosal reservoir. Increased ileal membrane permeability
      was observed only in rats subjected to 75 minutes of SMAO or SMAO 45/30.
      CONCLUSION: These results directly document that the levels of tumor necrosis
      factor-alpha and interleukin-6 released from the gut increase after an ischemic
      or I/R injury, such as SMAO, and that there is a relation between the magnitude
      of the gut ischemic or I/R insult and the cytokine response.

PMID- 10203081
TI  - Improved survival and reduction in local failure rates after preoperative
      radiotherapy: evidence for the generalizability of the results of Swedish Rectal
      Cancer Trial.
AB  - OBJECTIVE: The Swedish Rectal Cancer Trial (SRCT) demonstrated that a short-term
      regimen of high-dose preoperative radiotherapy (5 x 5 Gy) not only reduced the
      local recurrence rates but also improved the overall survival rate. This
      compelling evidence will have a significant impact on the primary treatment of
      rectal cancer. The authors' aim was to explore the representativeness of the
      study. SUMMARY BACKGROUND DATA: Until the SRCT was presented in 1997, no major
      trial had established that radiotherapy has a positive effect on the overall
      survival rate. METHODS: A review of all rectal cancer cases reported to the
      Swedish Cancer Registry during the same period that the SRCT accrued patients
      (1987 to 1990) was performed at 57 of 68 participating hospitals. At these 57
      hospitals, there were 2366 patients with invasive rectal cancer, with 1664 of
      these patients fulfilling the criteria for inclusion in the SRCT. RESULTS: Fifty
      two percent (866/1664) of eligible patients were included in the SRCT. The
      patients not included, of whom 8% (67/798) received adjuvant radiotherapy, had an
      overall 5-year survival rate of 48%, which was identical to the overall survival
      rate in the SRCT surgery-alone group (48%) but was inferior to the SRCT
      radiotherapy group (58%). The cancer-specific 5-year survival rates were 65% and
      66% among the patients not included and the surgery-alone group, respectively.
      The local recurrence rates reached 27% in both groups. The results were still
      comparable when stratifying for curative surgery, tumor stage, and surgical
      procedure. CONCLUSIONS: The achieved inclusion level of 52% in a randomized
      multicenter trial is comparatively high. Because the population in the SRCT was
      representative, it was concluded that the study results are reliable.

PMID- 10203082
TI  - Differential diagnosis of small polypoid lesions of the gallbladder: the value of
      endoscopic ultrasonography.
AB  - OBJECTIVE: To evaluate the accuracy of endoscopic ultrasonography (EUS) in making
      a differential diagnosis of small (< or =20 mm) polypoid lesions of the
      gallbladder. SUMMARY BACKGROUND DATA: Differential diagnosis of these lesions is
      often difficult using conventional imaging modalities. METHODS: The findings of
      EUS and transabdominal ultrasonography were retrospectively analyzed in 65
      surgical cases of small polypoid lesions (cholesterol polyp in 40,
      adenomyomatosis in 9, adenoma in 4, and adenocarcinoma in 12). RESULTS: Polypoid
      lesions exceeding 10 mm suggested malignancy. EUS showed a tiny echogenic spot or
      an aggregation of echogenic spots with or without echopenic areas in 95% of
      patients with cholesterol polyps. EUS showed multiple microcysts or comet tail
      artifact in all adenomyomatosis cases. Adenomas and adenocarcinomas were not
      associated with the echogenic spots, microcysts, or artifacts. Among adenomas and
      adenocarcinomas, all sessile lesions were adenocarcinomas. EUS differentiated
      among polypoid lesions more precisely than ultrasonography (97% vs. 71%).
      CONCLUSIONS: A tiny echogenic spot or an aggregation of echogenic spots and
      multiple microcysts or comet tail artifact is pathognomonic for cholesterol polyp
      and adenomyomatosis, respectively. Polypoid lesions without these findings
      indicate adenoma or adenocarcinoma on EUS. Routine use of EUS is recommended for
      differential diagnosis of polypoid gallbladder lesions when ultrasonography shows
      no signs indicative of either cholesterol polyp or adenomyomatosis.

PMID- 10203083
TI  - Effect of major hepatectomy on glucose and lactate metabolism.
AB  - BACKGROUND: The liver plays an important role in glucose and lactate metabolism.
      Major hepatectomy may therefore be suspected to cause alterations of glucose and
      lactate homeostasis. METHODS: Thirteen subjects were studied: six patients after
      major hepatectomy and seven healthy subjects who had fasted overnight. Glucose
      turnover was measured with 6,6(2)H glucose. Lactate metabolism was assessed using
      two complementary approaches: 13C-glucose synthesis and 13CO2 production from an
      exogenous 13C-labeled lactate load infused over 15 minutes were measured, then
      the plasma lactate concentrations observed over 185 minutes after lactate load
      were fitted using a biexponential model to calculate lactate clearance,
      endogenous production, and half-lives. RESULTS: Three to five liver segments were
      excised. Compared to healthy controls, the following results were observed in the
      patients: 1) normal endogenous glucose production; 2) unchanged 13C-lactate
      oxidation and transformation into glucose; 3) similar basal plasma lactate
      concentration, lactate clearance, and lactate endogenous production; 4) decreased
      plasma lactate half-life 1 and increased half-life 2. CONCLUSIONS: Glucose and
      lactate metabolism are well maintained in patients after major hepatectomy,
      demonstrating a large liver functional reserve. Reduction in the size of normal
      liver parenchyma does not lead to hyperlactatemia. The use of a pharmacokinetic
      model, however, allows the detection of subtle alterations of lactate metabolism.

PMID- 10203084
TI  - Influence of zero-balanced hemofiltration on the course of severe experimental
      pancreatitis in pigs.
AB  - OBJECTIVE: To examine the impact of continuous venovenous hemofiltration (CVVH)
      on the course of experimental pancreatitis in pigs. SUMMARY BACKGROUND DATA: The
      activation of different mediator cascades is assumed to trigger multiple organ
      dysfunction or failure during necrotizing pancreatitis. CVVH has been suggested
      to be beneficial in those instances by eliminating several inflammatory mediators
      released in the circulation. METHODS: Pancreatitis was induced by a combined
      intraductal injection of sodium taurocholate and enterokinase. Control group
      animals received no treatment after induction. A second group underwent
      "therapeutic" CVVH after a 20% decline of mean arterial pressure. In the third
      group, "prophylactic" CVVH was started simultaneously with the induction of
      pancreatitis. The concentrations of tumor necrosis factor-alpha, transforming
      growth factor-beta1, kinin, and phospholipase A2 were measured at different time
      points in blood (pre- and postfilter) and in the hemofiltrate to calculate the
      respective sieving coefficients that reflect most accurately the plasma clearance
      of mediators by CVVH. RESULTS: Survival time was significantly prolonged both by
      therapeutic and prophylactic CVVH; it was more pronounced in the latter. CVVH did
      not influence the increase in transforming growth factor concentrations. However,
      6 hours after induction, the increases of plasma concentrations of tumor necrosis
      factor, phospholipase, and kinin were significantly weakened by CVVH compared
      with controls. In the treatment groups, the plasma concentrations of tumor
      necrosis factor and phospholipase showed a significant negative correlation with
      the respective sieving coefficients, which decreased in the later course of the
      experiments. CONCLUSIONS: Experimental necrotizing pancreatitis was associated
      with a tremendous increase of plasma concentrations of tumor necrosis factor,
      phospholipase, and kinin. The effective removal of these mediators by CVVH
      resulted in significantly improved survival time. Animals that received
      prophylactic CVVH had a longer survival period than those in which CVVH was
      started after clinical impairment. The decreasing efficiency of CVVH in
      eliminating inflammatory mediators in the later course of the experiments
      suggested that the filter membranes were compromised by long-term application.
      These findings provide further evidence that CVVH offers therapeutic options even
      in the absence of conventional indications for blood-purifying treatments.

PMID- 10203085
TI  - Prognostic value of MIB-1 index and DNA ploidy in resectable ampulla of Vater
      carcinoma.
AB  - OBJECTIVE: To evaluate the prognostic value of the proliferative factors, MIB-1
      index, DNA ploidy, and S-phase fraction, and further to determine the independent
      prognostic factors in ampulla of Vater carcinoma after pancreaticoduodenectomy.
      SUMMARY BACKGROUND DATA: Cell kinetics are important indicators of the biologic
      behavior of various human tumors, but only a few authors have reported the
      application of cell proliferative factors in ampulla of Vater carcinoma. METHODS:
      Patients undergoing pancreaticoduodenectomy for ampulla of Vater carcinoma were
      included. Proliferative factors, MIB-1 index, and DNA contents, measured by flow
      cytometry, were evaluated and compared with the conventional clinicopathologic
      factors. RESULTS: Ninety resectable ampulla of Vater carcinomas were included. By
      univariate analysis, MIB-1 index, DNA ploidy, S-phase fraction, stage, and lymph
      node status were significant prognostic factors. The 5-year survival rate was
      40.7% for tumors with MIB-1 index < or =15% and 0% for those with MIB-1 index
      >15%. Diploid tumors had a significantly better prognosis than aneuploid.
      Outcomes of stage I and II tumors were more favorable than those of stage III and
      IV. After multivariate analysis, MIB-1 index, DNA ploidy, and stage remained as
      the independent prognostic factors. Among the three independent prognostic
      factors, MIB-1 index was the most powerful. CONCLUSIONS: Both MIB-1 index and DNA
      ploidy provide important prognostic value and potentially complement the
      conventional prognostic factors in resectable ampulla of Vater carcinoma. MIB-1
      index is the most powerful independent prognostic factor.

PMID- 10203086
TI  - Lessons learned from 500 cases of lymphatic mapping for breast cancer.
AB  - OBJECTIVE: To evaluate the factors affecting the identification and accuracy of
      the sentinel node in breast cancer in a single institutional experience. SUMMARY
      BACKGROUND DATA: Few of the many published feasibility studies of lymphatic
      mapping for breast cancer have adequate numbers to assess in detail the factors
      affecting failed and falsely negative mapping procedures. METHODS: Five hundred
      consecutive sentinel lymph node biopsies were performed using isosulfan blue dye
      and technetium-labeled sulfur colloid. A planned conventional axillary dissection
      was performed in 104 cases. RESULTS: Sentinel nodes were identified in 458 of 492
      (92%) evaluable cases. The mean number of sentinel nodes removed was 2.1. The
      sentinel node was successfully identified by blue dye in 80% (393/492), by
      isotope in 85% (419/492), and by the combination of blue dye and isotope in 93%
      (458/492) of patients. Success in locating the sentinel node was unrelated to
      tumor size, type, location, or multicentricity; the presence of lymphovascular
      invasion; histologic or nuclear grade; or a previous surgical biopsy. The false
      negative rate of 10.6% (5/47) was calculated using only those 104 cases where a
      conventional axillary dissection was planned before surgery. CONCLUSIONS:
      Sentinel node biopsy in patients with early breast cancer is a safe and effective
      alternative to routine axillary dissection for patients with negative nodes.
      Because of a small but definite rate of false-negative results, this procedure is
      most valuable in patients with a low risk of axillary nodal metastases. Both blue
      dye and radioisotope should be used to maximize the yield and accuracy of
      successful localizations.

PMID- 10203087
TI  - Do all patients with sentinel node metastasis from breast carcinoma need complete
      axillary node dissection?
AB  - OBJECTIVE: To determine the likelihood of nonsentinel axillary metastasis in the
      presence of sentinel node metastasis from a primary breast carcinoma. SUMMARY
      BACKGROUND DATA: Sentinel lymphadenectomy is a highly accurate technique for
      identifying axillary metastasis from a primary breast carcinoma. Our group has
      shown that nonsentinel axillary lymph nodes are unlikely to contain tumor cells
      if the axillary sentinel node is tumor-free, but as yet no study has examined the
      risk of nonsentinel nodal involvement when the sentinel node contains tumor
      cells. METHODS: Between 1991 and 1997, axillary lymphadenectomy was performed in
      157 women with a tumor-involved sentinel node. Fifty-three axillae (33.5%) had at
      least one tumor-involved nonsentinel node. The authors analyzed the incidence of
      nonsentinel node involvement according to clinical and tumor characteristics.
      RESULTS: Only two variables had a significant impact on the likelihood of
      nonsentinel node metastasis: the size of the sentinel node metastasis and the
      size of the primary tumor. The rate of nonsentinel node involvement was 7% when
      the sentinel node had a micrometastasis (< or =2 mm), compared with 55% when the
      sentinel node had a macrometastasis (>2 mm). In addition, the rate of nonsentinel
      node tumor involvement increased with the size of the primary tumor. CONCLUSIONS:
      If a primary breast tumor is small and if sentinel node involvement is
      micrometastatic, then tumor cells are unlikely to be found in other axillary
      lymph nodes. This suggests that axillary lymph node dissection may not be
      necessary in patients with sentinel node micrometastases from T1/T2 lesions, or
      in patients with sentinel node metastases from T1a lesions.

PMID- 10203088
TI  - Heparin and enoxaparin enhance endotoxin-induced tumor necrosis factor-alpha
      production in human monocytes.
AB  - OBJECTIVE: To determine whether heparin or the low-molecular-weight heparin
      enoxaparin alter lipopolysaccharide (LPS)-induced monocyte activation. SUMMARY
      BACKGROUND DATA: Heparin is widely used in clinical practice to inhibit the
      coagulation cascade. However, heparin also is a naturally occurring
      glucosaminoglycan and a pleiotropic immunomodulator that binds to a variety of
      proteins. LPS is a component of gram-negative bacteria and is thought to be
      responsible for many of the deleterious effects seen in sepsis. The binding of
      LPS to CD14 induces a signaling cascade that results in the release of many
      inflammatory mediators, including tumor necrosis factor-alpha (TNF-alpha).
      METHODS: Monocytes from healthy volunteers were isolated and cultured in the
      presence of saline, LPS (10 ng/ml), heparin (0.1 to 1000 microg/ml), or
      enoxaparin (0.1 to 1000 microg/ml). In blocking experiments, cells were
      pretreated for 60 minutes with the monoclonal anti-CD14 antibody MY4 (10
      microg/ml) or with isotype-matched control IgG2 (10 microg/ml). TNF-alpha values
      were measured with enzyme-linked immunosorbent assay. Significance was assessed
      with analysis of variance. RESULTS: Heparin (10 to 1000 microg/ml) and enoxaparin
      (1000 microg/ml) significantly enhanced LPS-induced TNF-alpha release. Heparin
      (1000 microg/ml) or enoxaparin (1000 microg/ml) did not produce TNF-alpha in the
      absence of LPS. Blockade of CD14 abrogated both LPS-induced TNF-alpha release and
      the effect of heparin or enoxaparin to enhance LPS-induced TNF-alpha release.
      CONCLUSIONS: The effect of heparin to enhance LPS-induced TNF-alpha release is a
      biologic phenomenon that reveals a novel and potentially important host defense
      mechanism during endotoxemia and sepsis. Binding of LPS to CD14 is necessary to
      induce this phenomenon, suggesting that both heparin and enoxaparin induce
      signaling mechanisms that are downstream from the initial binding of LPS on CD14.

PMID- 10203089
TI  - Imaging experimental intraabdominal abscesses with 99mTc-PEG liposomes and 99mTc
      HYNIC IgG.
AB  - OBJECTIVE: To evaluate the accuracy of technetium-99m-labeled polyethylene glycol
      coated liposomes (99mTc-PEG liposomes) and technetium-99m-labeled nonspecific
      human immunoglobulin G (99mTc-HYNIC IgG) for the scintigraphic detection of
      experimental intraabdominal abscesses in comparison with that of a standard
      agent, gallium-67 citrate. BACKGROUND: Scintigraphic imaging techniques can be
      very useful for the rapid and accurate localization of intraabdominal abscesses.
      Two newly developed radiolabeled agents, 99mTc-PEG liposomes and 99mTc-HYNIC IgG,
      have shown to be excellent agents for imaging experimental focal infection, but
      have not yet been studied in the detection of abdominal abscesses. METHODS:
      Intraabdominal abscesses were induced in 42 rats using the cecal ligation and
      puncture technique. Seven days later, randomized groups of rats received 99mTc
      PEG liposomes, 99mTc-HYNIC IgG, or 67Ga citrate intravenously. The rats were
      imaged up to 24 hours after the injection. The biodistribution of the radiolabel
      was determined by counting dissected tissues ex vivo. Macroscopic intraabdominal
      abnormalities and focal uptake on the images were independently scored on a
      semiquantitative scale. RESULTS: 99mTc-PEG liposomes provided the earliest
      scintigraphic visualization of the abscess (as soon as 2 hours after the
      injection vs. 4 hours for the other two agents). Liposomes, IgG, and gallium all
      showed similarly high absolute uptake in the abscess. Focal uptake of liposomes
      and gallium correlated best with the extent of the macroscopic abnormalities.
      CONCLUSIONS: 99mTc-PEG liposomes and 99mTc-HYNIC IgG performed at least as well
      as the standard agent, 67Ga citrate, in the detection of experimental
      intraabdominal abscesses, with obvious advantages such as lower radiation
      exposure and more favorable physical properties. Of the two technetium agents,
      the liposomes seemed to be superior, providing the earliest diagnostic image and
      the best correlation with the inflammatory abnormalities. In addition, the
      preferential localization of radiolabeled PEG liposomes holds promise for
      targeted delivery of liposome-encapsulated drugs.

PMID- 10203090
TI  - Acute hand burns in children: management and long-term outcome based on a 10-year
      experience with 698 injured hands.
AB  - OBJECTIVE: To document long-term results associated with an coordinated plan of
      care for acutely burned hands in children. SUMMARY AND BACKGROUND DATA: Optimal
      hand function is a crucial component of a high-quality survival after burn
      injury. This can be achieved only with a coordinated approach to the injuries.
      Long-term outcomes associated with such a plan of care have not been previously
      reported. METHODS: Over a 10-year period, 495 children with 698 acutely burned
      hands were managed at a regional pediatric burn facility; 219 children with 395
      injured hands were followed in the authors' outpatient clinic for at least 1 year
      and an average of >5 years. The authors' approach to the acutely burned hand
      emphasizes ranging and splinting throughout the hospital stay, prompt sheet
      autograft wound closure as soon as practical, and the selective use of axial pin
      fixation and flaps. Long-term follow-up, hand therapy, and reconstructive surgery
      are emphasized. RESULTS: Normal functional results were seen in 97% of second
      degree and 85% of third-degree injuries; in children with burns involving
      underlying tendon and bone, 70% could perform activities of daily living and 20%
      had normal function. Reconstructive hand surgery was required in 4.4% of second
      degree burns, 32% of third-degree burns, and 65% of those with injuries involving
      underlying bone and tendon. CONCLUSIONS: When managed in a coordinated long-term
      program, the large majority of children with serious hand burns can be expected
      to have excellent functional results.

PMID- 10203091
TI  - Auxiliary partial orthotopic liver transplantation for Crigler-Najjar syndrome
      type I.
AB  - OBJECTIVE: To determine if auxiliary partial orthotopic liver transplantation
      (APOLT) has the long-term potential to correct the underlying abnormality in
      Crigler-Najjar syndrome type 1 (CNS1) without the need for total liver
      replacement. BACKGROUND: Orthotopic liver transplantation has been used
      successfully to replace the defective enzyme in CNS1. Experimental studies have
      shown that only 1% to 2% of the normal hepatocyte mass is needed for bilirubin
      conjugation. If APOLT corrects the underlying metabolic abnormality, it has the
      advantage of preserving the native liver, which would serve as a "safety net"
      should the graft fail, and there is the potential for gene therapy in the future
      with possible withdrawal of immunosuppression. METHODS: Seven APOLT procedures
      were performed in six recipients with CNS1. Median age at transplantation was
      10.5 years. Six transplants were performed as a left auxiliary liver transplant,
      and one was performed as a right auxiliary liver transplant. Median serum
      bilirubin level at transplantation was 320 micromol/L. All patients required 12
      to 16 hours of phototherapy daily before the transplant to maintain serum
      bilirubin levels between 250 and 350 micromol/L. RESULTS: Median serum bilirubin
      level was 50 micromol/L at day 5 after the transplant and 23 micromol/L at a
      median follow-up of 32 months. In four children, early severe acute rejection
      developed, requiring conversion to tacrolimus; one underwent a second transplant
      for chronic rejection and graft atrophy but died from lymphoproliferative disease
      6 months after the second transplant. CONCLUSIONS: This report shows that APOLT
      is technically feasible and provides adequate hepatocyte mass to correct the
      underlying metabolic abnormality in CNS1.

PMID- 10203092
TI  - T-cell activation, proliferation, and memory after cardiac transplantation in
      vivo.
AB  - OBJECTIVE: To study the response of alloantigen (H2Kb)-specific T cells to a H2b+
      cardiac allograft in vivo. SUMMARY BACKGROUND DATA: The response of T cells to
      alloantigen has been well characterized in vitro but has proved more difficult to
      assess in vivo. The aim of these experiments was to develop a model of T-cell
      mediated rejection where the response of T cells after transplantation of a
      cardiac allograft could be followed in vivo. METHODS: Purified CD8+ T cells from
      H2Kb-specific TCR transgenic mice (BM3; H2k) were adoptively transferred into
      thymectomized, T-cell-depleted CBA/Ca (H2k) mice. These mice were then
      transplanted with a H2Kb+ cardiac allograft. Using four-color flow cytometry, the
      proliferative response, modulation of activation markers, and potential cytokine
      production of the H2Kb-specific T cells was assessed after transplantation.
      RESULTS: Consistent rejection of H2Kb+ cardiac allografts required the transfer
      of at least 6 x 10(6) CD8+ H2Kb-specific T cells. Short-term analyses revealed
      that the transgenic-TCR+/ CD8+ T cells proliferated and became activated after
      transplantation of an H2Kb+ cardiac allograft. Fifty days after transplantation,
      the transgenic-TCR+/CD8+ T cells remained readily detectable, bore a
      predominantly memory phenotype (CD44hi), and rapidly produced interleukin 2 and
      interferon-gamma on in vitro restimulation. CONCLUSIONS: These data show that the
      activation of alloantigen-specific T cells can be followed in vivo in short-term
      and long-term experiments, thereby providing a unique opportunity to study the
      mechanisms by which T cells respond to allografts in vivo.

PMID- 10203093
TI  - Role of pleural lavage cytology before resection for primary lung carcinoma.
AB  - OBJECTIVE: To investigate the role of pleural lavage cytology (PLC) in resection
      for primary lung carcinoma. SUMMARY BACKGROUND DATA: The prognostic significance
      of PLC before manipulation is still controversial. METHODS: Cytology of pleural
      lavage immediately after thoracotomy but before any manipulation of the lung was
      examined in 500 consecutive patients with lung cancer with no pleural effusion
      who underwent pulmonary resections. Eighteen patients who already had pleural
      dissemination were excluded from this study. RESULTS: Eighteen of 482 patients
      (3.7%) had positive cytologic findings. The positivity of PLC was significantly
      correlated with histology, extension of tumor to pleura, and presence of
      lymphatic permeation or vascular involvement by tumor. Positive lavage findings
      were seen only in adenocarcinoma. Because 6.3% of the patients with
      adenocarcinoma had positive cytologic findings, it is vital to perform PLC before
      curative resections for lung cancer, especially adenocarcinoma. The 5-year
      survival rates of the patients having negative and positive lavage findings were
      52.9% and 14.6%, respectively. The prognosis of the patients with positive lavage
      findings was as poor as that of the patients with stage IIIB disease and that of
      the patients with malignant effusion. CONCLUSIONS: Positive findings on PLC
      indicate exfoliation of cancer cells into the pleural cavity, which is an
      essential prognostic factor. In addition, we should regard positive cytologic
      findings as a subclinical malignant pleural effusion that is pathologic stage T4.

PMID- 10203094
TI  - Sternal wound infections in patients after coronary artery bypass grafting using
      bilateral skeletonized internal mammary arteries.
AB  - OBJECTIVES: This study evaluated the risks of sternal wound infections in
      patients undergoing myocardial revascularization using bilateral skeletonized
      internal mammary arteries (IMAs). BACKGROUND: The skeletonized IMA is longer than
      the pedicled one, thus providing the cardiac surgeon with increased versatility
      for arterial myocardial revascularization without the use of vein grafts. It is
      isolated from the chest wall gently with scissors and silver clips, and no
      cauterization is employed. Preservation of collateral blood supply to the sternum
      and avoidance of thermal injury enable more rapid healing and decrease the risk
      of sternal wound infection. METHODS: From April 1996 to August 1997, 545 patients
      underwent arterial myocardial revascularization using bilateral skeletonized
      IMAs. The right gastroepiploic artery was used in 100 patients (18%). The average
      age of the patients was 65 years; 431 (79%) were men and 114 (21%) were women;
      179 (33%) were older than 70 years of age; 166 (30%) were diabetics. The average
      number of grafts was 3.2 per patient. RESULTS: The 30-day operative mortality
      rate was 2% (n = 11). There were six perioperative infarcts (1.1%) and six
      strokes (1.1%); 9 patients had sternal infection (1.7%) and 15 (2.8%) had
      superficial infection. Risk factors for sternal infection were chronic
      obstructive pulmonary disease and emergency operation. Superficial sternal wound
      infections were more common in women and in patients with chronic obstructive
      pulmonary disease, renal failure, or peripheral vascular disease. The 1-year
      actuarial survival rate was 97%. Two of the six late deaths were not cardiac
      related. Late dehiscence occurred in three patients (0.6%). The death rate (early
      and late) of patients with any sternal complication was higher than that of
      patients without those complications (33% vs. 2.7%). CONCLUSIONS: Routine
      arterial myocardial revascularization using bilateral skeletonized IMAs is safe,
      and postoperative morbidity and mortality rates are low, even in elderly patients
      and those with diabetes. Chronic obstructive pulmonary disease and emergency
      operations were found to be associated with an increased risk of sternal
      infections, and the authors recommend avoiding the use of bilateral skeletonized
      IMAs in patients with these preoperative risk factors.

PMID- 10203095
TI  - Postgastrectomy osteopenia in minipigs.

PMID- 10203096
TI  - Parathyroid autotransplantation during thyroid surgery.

PMID- 10203097
TI  - Effects of methylprednisolone on human myeloid leukemic cells in vitro.
AB  - We have demonstrated previously that high-dose methylprednisolone treatment
      induces differentiation and apoptosis of leukemic cells in patients with
      different morphological subtypes of acute myeloblastic leukemia (AML) in vivo. In
      the present study, we investigated the in vitro effects of high (10(-3) M) and
      low (10(-6) M) concentrations of methylprednisolone (MP) on freshly isolated bone
      marrow leukemic cells from nine newly diagnosed patients with AML by light and
      electron microscopy (EM) and agarose gel electrophoresis. A marked increase in MP
      induced apoptosis of leukemic cells, with a maximum effect at 24 hr of exposure
      to both low and high concentrations of MP (10(-6) M and 10(-3) M), was
      demonstrated by light microscopy in cultures of four (three with AML-M1 and one
      with AML-M7) of the nine patients. In three cases, the increase in the number of
      apoptotic cells induced by high-concentration MP was approximately twice that
      observed when the lower concentration was used. A few apoptotic cells were
      detected in the cultures from the other five patients. However, a typical DNA
      ladder pattern of apoptosis was observed on gel electrophoresis of MP-treated
      leukemic cells from one patient (AML-M1) after 2 hr of incubation with both high-
      and low-MP concentrations. In two patients, a nonspecific DNA smear was observed
      only when high-concentration MP was used. The increase in differentiated leukemic
      cells induced by MP was also dose dependent, and was observed in cultures from
      all but one patient. Morphological features of apoptosis and differentiation were
      also confirmed by EM studies. The results of the present study, together with our
      previous clinical experience, suggest that MP, especially at high doses, could
      have a significant role in the treatment of some AML patients by inducing
      apoptosis and differentiation of leukemic cells.

PMID- 10203098
TI  - Modifications in accessibility of membrane glycoproteins, binding of specific
      ligands and coagulation factor V during the activation of platelets in blood
      emerging from bleeding time wounds.
AB  - Dual color flow cytometric techniques were applied to micro-aliquots of whole
      blood obtained from bleeding time (BT) wounds. Modifications in platelet
      activation markers (P-selectin [CD62P]) and lysosomal related protein (UMPS
      [CD63]), presence of membrane glycoproteins (GPIb [CD42b], GPIIb-IIIa [CD41a],
      GDIV [CD36], binding of von Willebrand factor (vWF), fibrinogen (Fg) and factor V
      [FV]) were analyzed in normal donors (n = 10) and in a severe von Willebrand
      patient (type 3) von Willebrand disease [vWD]). Samples of blood (20 microl) were
      sequentially removed from BT wound edges for up to 5 min and fixed with
      paraformaldehyde. Antigens were detected using the corresponding tagged
      monoclonal antibodies (moAbs) and quantitative results were referred to those
      found on platelet samples obtained from venous blood obtained from the same
      individuals. A progressive increase in % of platelets positive for activation
      dependent antigens (CD62 from 7 +/- 2 to 48 +/- 19% and CD63 from 9 +/- 1 to 44
      +/- 8%; initial vs. 4 min) was observed. Accessibility of GPIIb-IIIa epitopes on
      platelets from BT wounds remained slightly above levels observed in venous blood
      platelets, despite a progressive increase in the presence of platelets positive
      for Fgn. Binding of MoAb to GPIV increased at late stages of BT. A moderate
      decrease in the binding of a moAb to GPIb was observed on platelets obtained at
      late stages of the BT (14 +/- 9% and 20 +/- 6% at 4 and 5 min, respectively).
      This apparent decrease in GPIb epitopes paralleled an increased presence of
      platelets positive for vWF (26 +/- 12 and 38 +/- 15%). Binding of moAb to GPIb
      always remained above basal levels in platelets obtained from BTs performed in
      the patient with type 3 vWD. FV levels on platelets coming from the BT persisted
      at background levels in all the individuals and at all times studied.

PMID- 10203099
TI  - Role of positron emission tomography in determining the extent of CNS ischemia in
      patients with sickle cell disease.
AB  - Nearly 25% of patients with sickle cell disease (SCD) experience central nervous
      system morbidity involving both large and small vessel disease. Optimal imaging
      methods for determining the extent of ischemia are not known. Positron emission
      tomography (PET) has the unique ability to show tissue function as well as
      structure. Reports concerning patients with non-SCD neurodegenerative disorders
      suggest PET may be useful in determining prognosis. We compared magnetic
      resonance imaging, magnetic resonance angiography, and neuropsychological testing
      with PET prospectively. Six patients with SCD and a history of stroke, aged 10 to
      28, were enrolled. PET studies were performed on an ECAT HR 47 scanner
      (Siemens/CTI, Knoxville, TN) using 18-F-fluorodeoxyglucose as a tracer. PET
      interpretations were conducted in blinded fashion. MRI studies found two patients
      with only small vessel disease and four with both large and small vessel disease.
      In two of four subjects with large vessel disease, PET showed a corresponding
      metabolic abnormality and also identified an area of hypometabolism extending
      beyond the anatomical lesion as shown by MRI. PET did not demonstrate an
      abnormality corresponding with small vessel disease. Detailed neuropsychological
      testing demonstrated cognitive dysfunction in all cases. For some patients, PET
      may add sensitivity in detecting impaired metabolism in the area surrounding a
      major vessel infarct. However, the technique does not appear to be generally
      useful in characterizing small watershed or deep white matter infarcts. Larger
      studies, to include control subjects and carefully selected untransfused SCD
      patients, are needed. A combination of conventional imaging and
      neuropsychological testing remains the preferred evaluation for most SCD patients
      with neurologic symptoms.

PMID- 10203100
TI  - Hemostatic molecular markers before the onset of disseminated intravascular
      coagulation.
AB  - We retrospectively measured various hemostatic markers in 240 patients with
      disseminated intravascular coagulation (DIC) before the onset of DIC and in 110
      non-DIC patients, and examined their usefulness for the diagnosis of pre-DIC.
      Changes in prothrombin time ratio and fibrinogen levels were not significant
      before the onset of DIC. The plasma levels of fibrinogen and fibrin degradation
      products before the onset of DIC were increased and the platelet count was
      gradually reduced in nonleukemic patients; these changes were already significant
      in the non-DIC state. The plasma levels of thrombin-antithrombin complex (TAT),
      plasmin-plasmin inhibitor complex (PPIC), D-dimer, and soluble fibrin monomer
      (sFM) were increased before the onset of DIC. In leukemic patients, the plasma
      levels of sFM on day 5, those of TAT on day 3, and D-dimer on day 1, were
      significantly increased before the onset of DIC. The levels of most hemostatic
      markers 7 days before the onset of DIC were not different from those observed in
      the non-DIC state. In nonleukemic patients, only D-dimer, sFM, and TAT levels
      were significantly increased 7 days before the onset of DIC compared with values
      in the non-DIC state. The positive rate of hemostatic markers for the diagnosis
      of DIC, TAT, and PPIC were high during the pre-DIC and non-DIC groups. The plasma
      levels of sFM and D-dimer were low in non-DIC and increased gradually during the
      pre-DIC state. These findings suggest that hemostatic molecular markers such as
      sFM, D-dimer, and TAT are useful for the diagnosis of pre-DIC, although their
      cutoff values were different among various diseases.

PMID- 10203102
TI  - Autologous rosette formation by human blood monocyte-derived macrophages and
      lymphocytes.
AB  - The formation of rosettes between human blood monocyte-derived macrophages and
      lymphocytes (MLR) in samples harvested from total leukocyte (TL) cell cultures,
      was confirmed. Experiments with leukocytes obtained from human blood of healthy
      individuals (n = 17) and prepared under various conditions, were performed.
      Cytopreparations of each experiment were used for classical staining procedures
      or for immunohistochemical methods with monoclonal lymphocyte surface markers.
      Recently obtained blood leukocytes were unable to form MLR, whereas cultured
      samples of the same cells started to form MLR 15 hr after culturing. At that
      time, the number of MLR in pelleted samples was 1.18%, reaching a peak of 15.7%
      at 120 hr of culturing. In cultured but nonpelleted samples, only a few MLR were
      formed. With monoclonal antibodies, the lymphocytes forming MLR reacted mainly as
      CD4 positive and much less as CD8 (the ratio was 18:1). Monocyte-derived
      macrophages were able to form MLR when they underwent transformation into
      macrophages. The finding that the lymphocytes involved are T-cells, mainly CD4
      positive, suggests that in the cell-cell interaction, macrophages could be
      presenting antigens to the lymphocytes. Besides, because the highest number of
      MLR occurred in TL samples, whereas few rosettes were formed in the mononuclear
      cell samples, the existence of some particular mechanism(s) acting on TL samples
      is suggested.

PMID- 10203101
TI  - Hemoglobin S/O(Arab): thirteen new cases and review of the literature.
AB  - Hemoglobin S/O(Arab) (Hb S/O(Arab)) is a rare compound heterozygous
      hemoglobinopathy characterized by the presence of two variant beta-globin chains:
      beta6Glu --> Val (Hb S) and beta121Glu --> Lys (Hb O(Arab)). The diagnosis of Hb
      S/O(Arab) requires electrophoresis on both cellulose acetate and citrate agar,
      since Hb O(Arab) co-migrates with Hb C at alkaline pH and close to Hb S at acidic
      pH. To date only case reports and small series of patients with Hb S/O(Arab) have
      been described. To better characterize the clinical and laboratory aspects of
      this unusual disorder, we reviewed the Duke University Medical Center experience.
      We identified 13 African-American children and adults with Hb S/O(Arab) ranging
      in age from 2.7 to 62.5 years. All patients had hemolytic anemia with a median Hb
      of 8.7 gm/dL (range 6.1-9.9 gm/dL), and a median reticulocyte count of 5.8%
      (range 1.2-10.3%). The peripheral blood smear typically showed sickled
      erythrocytes, target cells, polychromasia, and nucleated red blood cells. All 13
      patients have had significant clinical sickling events including acute chest
      syndrome (11), recurrent vasoocclusive painful events (10), dactylitis (7),
      gallstones (5), nephropathy (4), aplastic crises (2), avascular necrosis (2), leg
      ulcers (2), cerebrovascular accident (CVA) (1), osteomyelitis (1), and
      retinopathy (1). Four patients have died, including two from pneumococcal
      sepsis/meningitis at ages 5 and 10 years, one of acute chest syndrome at age 14
      years, and one of multiorgan failure at age 35 years. We conclude that Hb
      S/O(Arab) disease is a severe sickling hemoglobinopathy with laboratory and
      clinical manifestations similar to those of homozygous sickle cell anemia.

PMID- 10203103
TI  - Assessment of iron stores in children with transfusion siderosis by biomagnetic
      liver susceptometry.
AB  - To investigate the applicability of noninvasive Superconducting Quantum
      Interference Device (SQUID) biomagnetic liver susceptometry and its limitations
      in thalassemic children, 23 patients with beta-thalassemia major and other iron
      loading anemias (age: 4-16 years) and 16 age-related normal children were
      studied. Liver iron concentrations ranged from 600 to 11,000 microg/g(liver) for
      thalassemic patients and from 60 to 340 microg/g(liver) for normal patients.
      Measuring the respective organ volumes by sonography, liver and spleen iron
      stores, accounting for 80% of total body iron stores, were estimated. Nonliver
      contributions from the lung or intestine to the measured SQUID signals in the
      small-sized patients were not observed. Moreover, livers in thalassemia were
      found to be enlarged by 18% per 1,000 microg/g (r = 0.75, P < 10(-3)). Serum
      ferritin values correlate significantly with iron stores (r = 0.64, P < 10(-3)),
      but predict iron stores only within large error intervals of 4,000
      microg/g(liver). Analyzing the experimental data from biomagnetometry and from
      related transfusion and chelation treatment data within the framework of a two
      compartment model, we were able to derive additional information on total body
      iron elimination and chelation therapy efficacy. The exponential decline of iron
      stores allows forecast of steady-state conditions of the final iron load for a
      particular transfusion and chelation therapy regimen.

PMID- 10203104
TI  - Acute promyelocytic leukemia after treatment for non-Hodgkin's lymphoma with
      drugs targeting topoisomerase II.
AB  - We report a patient who developed acute promyelocytic leukemia (APL)
      concomitantly with a second relapse of non-Hodgkin's lymphoma (NHL), intermediate
      grade, WF type E. At diagnosis and at first NHL relapse, the patient had received
      the same chemotherapy regimen, which included drugs targeting DNA topoisomerase
      II, i.e., etoposide (total dose 5,760 mg) and idarubicin (total dose 180 mg).
      Thirty-eight months after initial treatment, the patient showed pancytopenia
      associated with lymphoma recurrence. Bone marrow examination revealed the
      presence of atypical promyelocytes with Auer rods; cytogenetics showed t(15;17),
      and molecular analysis detected promyelocytic leukemia-retinoic acid receptor
      alpha rearrangement. APL reached complete remission after all trans retinoic acid
      therapy, whereas NHL did not respond to further chemotherapy. In the literature,
      five other patients developed APL after treatment for lymphoma, from a total of
      59 patients developing sAPL after treatment for any type of neoplasia.

PMID- 10203105
TI  - Abnormal proliferation of CD4- CD8+ gammadelta+ T cells with chromosome 6
      anomaly: role of Fas ligand expression in spontaneous regression of the cells.
AB  - We report a case of granular lymphocyte proliferative disorder accompanied with
      hemolytic anemia and neutropenia. Phenotypes of the cells were T cell receptor
      gammadelta+ CD3+ CD4- CD8+ CD16+ CD56- CD57-. Southern blot analysis of T cell
      receptor beta and gamma chains demonstrated rearranged bands in both. Chromosomal
      analysis after IL-2 stimulation showed deletion of chromosome 6. Sorted
      gammadelta+ T cells showed an increase in Fas ligand expression compared with the
      levels in sorted alphabeta+ T cells. The expression of Fas ligand on these
      gammadelta+ T cells increased after IL-2 stimulation. The patient's anemia
      improved along with a decrease in granular lymphocyte count and disappearance of
      the abnormal karyotype without treatment. The expression of Fas ligand may be
      involved in spontaneous regression of granular lymphocyte proliferation with
      hemolytic anemia.

PMID- 10203106
TI  - Identification of a new candidate mutation, G1629R, in a family with type 2A von
      Willebrand disease.
AB  - Type 2A is a qualitative variant of von Willebrand disease (vWD) characterized by
      a reduced platelet-dependent function, associated with an absence of large
      multimers. A G5135A transition, resulting in a glycine to arginine substitution
      at the codon 1629 of the von Willebrand factor, was identified by automated
      sequencing in one type 2A vWD Spanish patient. To detect this new candidate
      mutation a modified primer that creates a Ddel restriction site when the mutation
      is present was designed. This approach allowed detection of the mutation in the
      other three patients from the same family. On the other hand, the fact that this
      new mutation was not found in the 110 normal alleles screened further supports
      their causal relationship with the disease.

PMID- 10203107
TI  - All-trans retinoic acid-induced multiple mononeuropathies.

PMID- 10203108
TI  - Soft drink abuse, malnutrition, and folic acid deficiency.

PMID- 10203109
TI  - Sex difference in myeloperoxidase activity of neutrophils.

PMID- 10203110
TI  - Case of hepatosplenic gammadelta T-cell lymphoma presenting with severe
      hypersplenism.

PMID- 10203111
TI  - Effectiveness of preventive in-home geriatric assessment in well functioning,
      community-dwelling older people: secondary analysis of a randomized trial.
AB  - OBJECTIVES: To determine whether preventive in-home comprehensive geriatric
      assessment (CGA) prevents functional decline in community-dwelling older persons
      with different baseline functional status: (1) without any basic activities of
      daily living (BADL) dependency at baseline; and (2) without any instrumental ADL
      (IADL) and basic ADL dependency at baseline. DESIGN: Subgroup analyses of a 3
      year randomized controlled trial. SETTING: The city of Santa Monica, California.
      PARTICIPANTS: Participants came from the original population (n = 414) of
      community-living older persons aged 75 years and older who participated in a
      trial testing the effectiveness of annual preventive in-home CGA. For the first
      subgroup analysis, we excluded subjects (n = 27) who were dependent in one or
      more BADL before randomization (final sample size, n = 387); for the second
      subgroup analysis, we excluded 93 additional subjects who were dependent in one
      or more IADL before randomization (final sample size, n = 294). INTERVENTION:
      Annual preventive in-home CGA, with quarterly home visits by gerontologic nurse
      practitioners, for 3 years. MEASUREMENTS: Functional status data were collected
      through yearly in-home interviews by independent observers. Subjects were
      classified as (1) independent in both BADL and IADL, (2) dependent in IADL but
      independent in BADL, or (3) dependent in both IADL and BADL. RESULTS: In both
      subgroup analyses, there was no difference in survival between intervention and
      control subjects. In the subgroup with no BADL impairment at baseline,
      intervention subjects spent significantly fewer days dependent in both BADL and
      IADL during each year of the study (5 days vs 14 days, P = .022; 13 vs 33, P =
      .016; and 19 vs 44, P = .014 for years 1, 2, and 3, respectively) and over all 3
      years combined (36 days vs 92 days, P = .016) in bivariate analyses. In
      multivariate analyses, the intervention reduced time spent in complete (BADL and
      IADL) dependency (P = .028). In the subgroup of subjects without any IADL or BADL
      impairment at baseline, no significant differences were apparent in the number of
      days spent in complete independence and days spent in complete dependency.
      Intervention group subjects spent more days in partial dependency during Year 1
      (24 days vs 9 days, P = .021), but the difference was not significant during Year
      2 (47 vs 29, P = .088), Year 3 (49 vs 41, P = .370), and over all 3 years
      combined (120 vs 79, P = .123) as well as in multivariate analysis (P = .062).
      CONCLUSION: These findings support the hypothesis that in-home preventive visits
      delay the onset of disability in people without initial BADL impairment. Further
      studies in larger samples are needed to determine optimal intervention strategies
      and effectiveness among well functioning older people.

PMID- 10203112
TI  - Alcohol consumption is negatively associated with the prevalence of coronary
      heart disease in the New Mexico Elder Health Survey.
AB  - OBJECTIVE: To compare the prevalence of coronary heart disease (CHD) and the
      effects of various risk factors, including alcohol consumption, on prevalence
      rates in a randomly selected sample of older Hispanic and non-Hispanic white
      (NHW) men and women. DESIGN AND SETTING: A cross-sectional study of equal numbers
      of Hispanic and NHW men and women, selected randomly from Health Care Financing
      Authority (Medicare) rolls, recruited for a home interview followed by a 4-hour
      interview/examination in a senior health clinic. PARTICIPANTS: A total of 883
      volunteers, mean age 74.1, years were interviewed/examined. MEASUREMENTS: CHD was
      identified by interview and electrocardiogram. Risk factors were identified by
      interview (hypertension, diabetes, medications, smoking, alcohol consumption) and
      by direct measurements (glucose tolerance, serum lipids, blood pressure,
      anthropometry). RESULTS: The age-adjusted prevalences of CHD were not
      significantly different when Hispanic men and women were compared with their NHW
      counterparts. Age-, ethnicity-, and gender-adjusted relative risk of CHD was
      inversely associated with alcohol consumption (OR .46; 95% CI, .28-.73; P <
      .001). Hypertension, diabetes mellitus, and male gender were also significant
      risk factors; age, anthropometric measurements, smoking, serum lipid
      concentrations, and level of education were not. HDL cholesterol levels were
      significantly lower in nondrinkers; other lipid levels were not associated with
      alcohol consumption. The type of alcoholic beverage was not associated with the
      prevalence of CHD. CONCLUSIONS: No significant differences in CHD prevalence
      existed between Hispanic and NHW participants despite a higher prevalence of
      diabetes and central obesity in Hispanics. Alcohol consumption was strongly
      negatively associated with the prevalence of CHD identified in this older,
      biethnic population.

PMID- 10203113
TI  - The predictive value of combined hypoalbuminemia and hypocholesterolemia in high
      functioning community-dwelling older persons: MacArthur Studies of Successful
      Aging.
AB  - OBJECTIVES: To examine the effect of simultaneous hypoalbuminemia and
      hypocholesterolemia levels on 3- and 7-year rates of mortality and decline in
      functional status. METHODS: In this cohort study, 937 community-based persons
      aged 70 to 79 years in 1988, who had high baseline physical and cognitive
      functioning, were classified into four groups: Group 1 (low albumin, low
      cholesterol), Group 2 (low albumin, normal cholesterol), Group 3 (normal albumin,
      low cholesterol) and Group 4 (normal albumin, normal cholesterol) using baseline
      blood values. Crude and multiply adjusted rates of (1) mortality (2) decline in
      Rosow-Breslau (RB) functional status, and (3) mortality or decline in RB
      functional status in 1991 and 1995 were calculated. RESULTS: Group 1 subjects had
      multiply adjusted relative risks (ARR) of 3.62 and 3.53 for 3-and 7-year
      mortality compared with Group 4. Group 1 subjects had ARRs of 3.82, 3.02, and
      2.67 of 3-year mortality or decline in RB activity scale when compared with
      Groups 4, 2, and 3, respectively. CONCLUSIONS: Concomitant low serum cholesterol
      and albumin levels may identify high functioning older persons who are at
      increased risk of subsequent mortality and functional decline.

PMID- 10203114
TI  - Atrial natriuretic peptide and the development of congestive heart failure in the
      oldest old: a seven-year prospective study.
AB  - BACKGROUND: Atrial natriuretic peptide (ANP) levels are elevated in symptomatic
      heart failure and correlate with invasively measured left heart pressures.
      OBJECTIVE: To examine the association between plasma ANP level and the subsequent
      development of congestive heart failure (CHF) in older subjects with no history
      of CHF. DESIGN: A 7-year, prospective, blinded, cohort study. SETTING: A life
      care facility in Boston, Massachusetts. PARTICIPANTS: Two hundred fifty-six frail
      older subjects (mean age 88 +/- 7) with no history of CHF at study entry. MAIN
      OUTCOME MEASURE: Clinical episodes of CHF with confirmatory chest roentgenogram
      findings. Cox proportional hazard analyses were performed to examine the
      relationship between ANP levels and the development of CHF while controlling for
      19 clinical, physical, and laboratory parameters. A Kaplan-Meier estimator (log
      rank test) was used to determine if the development of CHF differed by tertile of
      ANP. RESULTS: During the follow-up period, 32% of the cohort developed CHF. The
      mean ANP level in the CHF group was 95 pmol/L +/- 11 pmol/L versus 60 pmol/L +/-
      5 pmol/L in the no CHF group (two tailed t test P = .005). On multivariate
      analysis, a high ANP level was found to be associated significantly (P = .01)
      with the development of CHF. CONCLUSIONS: There is a statistically significant
      association between ANP level and the subsequent development of CHF in frail
      older individuals with no history of CHF.

PMID- 10203115
TI  - Drinking habits among older persons: findings from the NHANES I Epidemiologic
      Followup Study (1982-84). National Health and Nutrition Examination Survey.
AB  - OBJECTIVES: To describe alcohol use and its sociodemographic correlates among
      persons aged 65 years and older in a US probability sample. DESIGN: Cross
      sectional analysis of a national probability sample-based cohort study. SETTING:
      Multiple sites throughout the United States. PARTICIPANTS: A total of 3448
      persons aged 65 and older who participated in the first wave of the NHANES I
      Epidemiologic Followup Study (1982-84). MEASUREMENTS: We describe the alcohol use
      behaviors and demographic characteristics of 3448 persons aged 65 and older.
      Least squares regression models were used to assess associations between older
      persons' sociodemographic characteristics and alcohol use. RESULTS: Sixty percent
      of the sample reported having 12 or more drinks of alcohol in at least 1 year of
      their lives. Seventy-nine percent of these older drinkers were currently
      drinking. Twenty-five percent of all drinkers drank daily (31% men, 19% women).
      Using gender-specific definitions (men >2 drinks/day; women >1 drink/day), 16% of
      men drinking alcohol and 15% of women drinking alcohol were heavy drinkers.
      Younger age, male gender, and higher income were associated with greater alcohol
      use. CONCLUSIONS: Most older persons who ever drank alcohol in their lifetimes
      were currently drinking. In addition, a substantial number of older persons were
      drinking currently at levels that may place them at risk of adverse health
      consequences.

PMID- 10203116
TI  - Measures of disease control in Medicare beneficiaries with diabetes mellitus.
AB  - OBJECTIVE: To investigate measures of disease control for Medicare beneficiaries
      with diabetes and their outpatient care in the fee-for-service setting. DESIGN:
      Retrospective cohort study. SETTINGS: Office practices in Alabama, Iowa, and
      Maryland of 293 primary care physicians (PCPs) who volunteered to participate in
      the Ambulatory Care Quality Improvement Project. PARTICIPANTS: A total of 5980
      patients with an average age of 75.2 years. MEASUREMENTS: For an 18-month period
      (1/1/94-6/30/95), medical records were abstracted for clinical parameters,
      including up to four blood glucose values; two blood pressure measurements; one
      total cholesterol value; two serum creatinine values; medication use, including
      antihypertensives, angiotensin-converting enzyme (ACE) inhibitors, and lipid
      lowering agents; and frequency of glycosylated hemoglobin (GHb) determinations.
      RESULTS: During the study, 44% of patients received at least one GHb
      determination, 94% received at least one blood glucose, 68% at least one total
      serum cholesterol, 74% at least one serum creatinine test, and 97% at least one
      blood pressure measurement. Ten percent of patients had mean blood glucose levels
      > or = 250 mg/dL. Eighty-five percent had evidence of hypertension. Of this group
      of hypertensive patients with blood pressure readings available, 70% had blood
      pressure readings > or = 140/90 mm Hg, even though there were on medication that
      could have been prescribed for hypertension. Thirty-six percent of those who had
      evidence of hypertension were taking an ACE inhibitor. Thirty-two percent of
      those taking lipid-lowering medication had a total serum cholesterol value > or =
      240 mg/dL. Statistically significant differences were noted for age and gender,
      with men and patients more than 85 years old generally having better measures of
      disease control. CONCLUSIONS: Many older Medicare patients with diabetes did not
      achieve recommended target levels of blood glucose, blood pressure, and lipids.
      GHb and serum cholesterol are not being monitored at recommended intervals.
      Significant opportunities exist to improve diabetes care for this population.

PMID- 10203117
TI  - Diabetes and dementia in long-term care.
AB  - OBJECTIVES: To examine the presence or absence of dementia, and the prevalence
      rates for different dementias, in patients with and without adult onset diabetes
      (AODM). DESIGN: Chart survey. SETTING: A public long-term care facility in
      Rochester, New York, chosen to provide an enriched sample with respect to the
      diseases and demographic variables of interest. PARTICIPANTS: All long-term care
      residents in the facility aged 50 years or older (n = 476), mean age 74.8 years.
      Thirty-six (7.6%) had probable Alzheimer's disease (AD), 49 (10.3%) had possible
      AD, 38 (8.0%) had clinically diagnosed vascular dementia, 84 (17.6%) had
      unspecified dementias, and 269 (56.5%) were not demented. MEASUREMENTS:
      Demographic data, dementia and diabetes determined on the basis of extraction of
      chart data, and hypertension, myocardial infarction, congestive heart failure,
      and hypercholesterolemia determined on the basis of chart diagnoses. RESULTS:
      There were 99 residents with AODM in the sample, a prevalence rate of about 21%.
      The rates of both dementia and AODM were as expected for this age group and
      setting. Patients with probable or possible AD had the lowest rates of AODM (0
      and 6.1%, respectively), and patients with vascular dementia had the highest
      rates of AODM (47.4%). Age, sex, and race influenced both the risk of having a
      dementia and the type of dementia. When these variables were adjusted for in
      multiple logistic regression, however, AODM remained a robust predictive factor
      because of its significant negative association with AD. Patients with
      unspecified dementias and no dementia showed rates of AODM (about 20%) that were
      roughly comparable and intermediate between vascular dementia and AD.
      CONCLUSIONS: In our study, AD diagnosed clinically and AODM did not co-occur,
      whereas AODM was associated with vascular dementia diagnosed clinically.
      Conversely, in non-Alzheimer, nonvascular dementias diagnosed clinically, the
      rates of AODM were equivalent to those in nondemented patients. These findings
      are in agreement with some, but not all, previous studies.

PMID- 10203118
TI  - The nursing home at night: effects of an intervention on noise, light, and sleep.
AB  - OBJECTIVES: The sleep of nursing home residents is fragmented by frequent
      awakening episodes associated, at least in part, with environmental variables,
      including noise and light changes. The purpose of this study was to improve sleep
      by reducing the frequency of nighttime noise and light changes. PARTICIPANTS AND
      SETTING: Two hundred sixty-seven incontinent nursing home residents in eight
      nursing homes. DESIGN: A randomized control group design with a delayed
      intervention for the control group. MEASUREMENTS: Bedside noise and light
      monitors recorded the number of 2-minute intervals at night with peak sounds
      recorded above 50 dBs and the number of light changes of at least 10 lux between
      adjacent 2-minute intervals. Daytime behavioral observations measured sleep and
      in-bed time during the day, and wrist activity was used to estimate sleep at
      night. Awakening events associated with the environmental variables were derived
      from the wrist activity data. INTERVENTION: A behavioral intervention implemented
      between 7:00 p.m. and 6:00 a.m. that involved feedback to nursing home staff
      about noise levels and implementation by research staff of procedures to both
      abate noise (e.g., turn off unwatched television sets) and to individualize
      nighttime incontinence care routines to be less disruptive to sleep. RESULTS:
      Noise was reduced significantly, from an average of 83 intervals per night with
      peak noises recorded above 50 dBs to an average of 58 intervals per night in the
      group that received the initial intervention, whereas noise in the control group
      showed no change (MANOVA group x time P < .001). All 10-dB categories of noise
      from 50 to 90+ dBs were reduced, and light changes were reduced from an average
      of four per night per resident to two per night (P < .001). Despite these
      significant changes in the environmental variables, there was a significant
      differential improvement in the intervention group on only two night sleep
      measures: awakening associated with a combination of noise plus light (P < .001)
      and awakening associated with light (P < .001). However, there was a significant
      correlation between change in noise and change in percent sleep from baseline to
      intervention (r = -.29, P < .05), suggesting that the intervention did not reduce
      noise to low enough levels to produce a significant improvement in sleep. The
      intervention effects on all environmental variables were replicated in the
      delayed intervention group, who again showed significant improvement on the same
      sleep measures. Observations of day sleep and in-bed time did not change over the
      phases of the trial for either group. CONCLUSION: The significant reductions in
      noise and light events resulting from the intervention did not lead to
      significant improvements in the day sleep and most night sleep measures. An
      intervention that combines both behavioral and environmental strategies and that
      addresses daytime behavioral factors associated with poor sleep (e.g., excessive
      time in bed) would potentially be more effective in improving the night sleep and
      quality of life of nursing home residents.

PMID- 10203119
TI  - Severe disruptive vocalizers.
AB  - OBJECTIVES: To describe the most severe disruptive vocalizers in nursing
      facilities, in regard to their clinical and behavioral characteristics, staff
      responses, and treatments used, and to report on their prognosis over 6 months.
      DESIGN: A longitudinal cohort study. SETTING: One hundred seven skilled nursing
      facilities. PARTICIPANTS: The 203 residents who were among the two most
      disruptive vocalizers in their respective facilities and who vocalized at least 2
      hours a day. MEASUREMENTS: Telephone interviews of licensed nursing staff who
      cared for the subjects, conducted at baseline, 2, 4, and 6 months. Data gathered
      included subject demographics, physical function, diagnoses, medication and
      restraint use, behavioral problems, vocalization characteristics, treatments
      used, and status at follow-up. RESULTS: Subjects tended to have dementia, to be
      dependent in most activities of daily living, to have multiple medical problems,
      to be physically restrained (48%), and to be taking psychotropic medication
      (76%). Nearly all (95%) were audible at least 50 feet away, with loudness
      associated with more severe cognitive impairment (OR 4.90, P = .001). When
      subjects who primarily made nonverbal noises ("screamers") were compared with
      those whose predominant expressions were words ("talkers"), hearing impairment,
      severe cognitive impairment, and greater dependency in activities of daily living
      characterized the screamers. Staff reported trying a variety of treatments with
      all subjects, often with little success. Two months after enrollment, 66% of
      surviving subjects vocalized fewer hours than at baseline, and 45% were rated as
      improved. Independent predictors of improvement included greater ADL
      independence, hearing and vision problems, shorter length of stay, urinary
      incontinence, and use of a treatment other than one-on-one interventions. Nearly
      one-quarter of subjects (23.4%) died within 6 months. Baseline factors associated
      independently with a higher probability of death included age, use of activity
      intervention, physical abusiveness, and absence of wandering. CONCLUSION: Severe
      disruptive vocalization is associated with severe cognitive and physical
      impairment and with a high probability of mortality within 6 months.
      Subcategorization of severe vocalizers by vocalization type or other associated
      factors may be useful for prognostic and treatment purposes.

PMID- 10203120
TI  - Evaluation of Simulated Presence: a personalized approach to enhance well-being
      in persons with Alzheimer's disease.
AB  - OBJECTIVE: To evaluate the efficacy of Simulated Presence, a personalized
      approach to enhance well-being among nursing home residents with Alzheimer's
      disease and related dementia's (ADRD). DESIGN: Latin-Square, double blinded, 3
      factor design with restrictive randomization of three treatments (the study
      intervention, a placebo audio tape of a person reading the newspaper, and usual
      care). The three factors were treatment, time, and facility type. SETTING: Nine
      nursing homes in Eastern Massachusetts and Southern New Hampshire. PARTICIPANTS:
      Fifty-four subjects with documented ADRD who were aged 50 years or older,
      medically stable, had resided in their current nursing home for at least 3
      months, and who had no planned discharge. All subjects had a history of agitated
      or withdrawn behaviors. INTERVENTION: The purpose of Simulated Presence is to
      provide a personalized intervention for persons with moderate to severe cognitive
      impairment. Through a unique testing process, some of the best loved memories of
      the ADRD person's lifetime are identified and then those memories are introduced
      to the patient in the format of a telephone conversation using a continuous play
      audio tape system. The intervention may be used for extended periods of time
      because each repetition is viewed as a fresh, live telephone call as a result of
      the short-term memory deficit of the person with ADRD. MEASUREMENTS: Direct
      observations of outcomes included using a newly developed scale, the Scale for
      the Observation of Agitation in Persons with Dementia, an agitation visual analog
      scale, the Positive Affect Rating Scale (mood and "interest"), a withdrawal
      visual analog scale, and facial diagrams of mood. Reported measures included
      daily staff observation logs of responses to interventions offered, and weekly
      staff surveys using the short-form Cohen-Mansfield Agitation Inventory and the
      Multidimensional Observation Scale for Elderly Subjects (mood and "interest").
      Severity of dementia was assessed by the Mini-Mental State Exam, the Test for
      Severe Impairment, the Bedford Alzheimer's Nursing Scale, and the ADL Self
      Performance Scale. RESULTS: Chi-square analysis of direct observations, using
      facial diagrams, revealed that Simulated Presence was equivalent to usual care (P
      = .141) and superior to placebo for producing a happy facial expression (P =
      .001). A positive effect was also documented in nursing staff observation logs
      using Analysis of Variance techniques (ANOVA) for subjects during Simulated
      Presence phases compared with the placebo phases (P < .001) and usual care phases
      (P < .001). According to ANOVA analyses of "interest" from weekly surveys,
      Simulated Presence was superior to both usual care (P = .001) and placebo (P =
      .008). We were unable to find evidence of significant differences (P < .05) among
      interventions for other direct observations and weekly reports of overall
      agitation or mood aspects of withdrawal. Subjects accepted the intervention most
      of the time, except for five subjects who refused it more than 50% of the time.
      CONCLUSION: This study provided evidence that Simulated Presence can be effective
      in enhancing well-being and decreasing problem behaviors in the nursing home
      setting as a substitute for or complement to usual care.

PMID- 10203121
TI  - Religious activity improves life satisfaction for some physicians and older
      patients.
AB  - OBJECTIVE: To assess religious perceptions and activities of physicians and older
      patients and to determine whether religious activities are associated with life
      satisfaction. DESIGN AND SETTING: A cross-sectional survey of practicing Virginia
      internists and psychiatrists and hospitalized or institutionalized (nursing home)
      older adults. PARTICIPANTS: One hundred randomly sampled practicing physicians
      and 55 hospitalized or institutionalized older patients. METHODS: A mailed survey
      was used for the physicians and a structured interview for the patients. All
      subjects provided information pertaining to demographics and life satisfaction
      using the Life Satisfaction Index (LSI-B). For physicians or patients who engaged
      in any religious activity, the Intrinsic/Extrinsic Religiosity (I/E-R) scale was
      used. RESULTS: Of the 100 physicians (49 internists and 51 psychiatrists) who
      answered the survey (50% response rate), 75% used religious activity as a coping
      resource (39% somewhat, 36% definitely). There was a positive correlation between
      intrinsic religious activity (e.g., prayer, Bible reading) and life satisfaction
      (r = .293, P = .042). Of the 55 patients interviewed, 47 (86%) used religion as a
      coping resource, and intrinsic religious activity was positively associated with
      life satisfaction (r = .843, P < .001). Even after controlling for age, gender,
      health, and marital status, intrinsic religious activity remained a predictor of
      higher life satisfaction. CONCLUSIONS: Intrinsic religious activity is associated
      positively with life satisfaction in physicians and ill older adults.

PMID- 10203122
TI  - Functional impairment in instrumental activities of daily living: an early
      clinical sign of dementia?
AB  - OBJECTIVE: To estimate the predictive value of four IADLs on 3- and 5-year
      incident dementia. DESIGN: Prospective cohort study. SETTING: A community survey
      in 37 randomly selected parishes. SUBJECTS: A random sample of French community
      dwellers aged 65 and older included in the PAQUID study followed-up at 3 (1582
      subjects) and 5 years (1283 subjects). MAIN OUTCOME MEASURES: Incidence of
      dementia at 3 and 5 years, diagnosed by two-step screening: (1) MMS and DSM-III
      R; (2) diagnosis of dementia confirmed by a neurologist. RESULTS: A score summing
      up the number of dependencies at baseline on four IADLs is a predictor of 3-year
      but not of 5-year incident dementia. Increase in the level of dependence between
      baseline and 3-year follow-up is associated with an increased risk of incident
      dementia at 5-year follow-up. CONCLUSION: These four IADLs can help to identify
      older subjects at high risk of dementia who should then undergo
      neuropsychological testing.

PMID- 10203123
TI  - Equilibrium and limb coordination in mild cognitive impairment and mild
      Alzheimer's disease.
AB  - OBJECTIVE: To examine changes in equilibrium and limb coordination in normal
      aging, mild cognitive impairment, and moderate cognitive impairment associated
      with early probable Alzheimer's disease (AD), by means of parametric clinical
      measures. DESIGN: Case series SETTING: Out-patient clinic. PARTICIPANTS: A
      consecutive sample of 365 community-residing ambulatory volunteers (137 men, 228
      women; mean age 70.4 +/- 9.4 years; mean educational attainment 14.6 +/- 3.1
      years), who were followed in an ongoing longitudinal study of aging and AD,
      comprising cognitively intact individuals, persons with mild cognitive
      impairment, and patients with mild AD. MEASUREMENTS: For general magnitude of
      cognitive function, the Global Deterioration Scale (GDS). For cognition, the Mini
      Mental State Examination (MMSE). Equilibrium was assessed with parametric
      measurements of single leg stance (SLS) and tandem walking (TW). Limb
      coordination was assessed with parametric measurements of foot tapping (FT),
      alternating pronation and supination (PS), and sequential finger to thumb tapping
      (FTH). MAIN RESULTS: After adjustment for age, persons with mild cognitive
      impairment or mild AD had significantly poorer performance on parametric clinical
      tests of equilibrium and limb coordination compared with cognitively intact
      individuals (P < .05). CONCLUSIONS: Changes in equilibrium and limb coordination
      are clinically demonstrable in persons with mild cognitive impairment and mild AD
      using simple parametric tests. Such tests could potentially identify individuals
      with increased risk of falling. Early diagnosis and treatment of conditions that
      can jeopardize equilibrium and limb coordination, as well as balance and
      coordination training, might help cognitively impaired older people to maintain
      optimal function and may decrease the risk of falls and injuries.

PMID- 10203124
TI  - Medical cost for disability: a longitudinal observation of national health
      insurance beneficiaries in Japan.
AB  - OBJECTIVES: To measure the impact of disability on the use of medical care and
      its costs. DESIGN: A 1-year prospective cohort study of National Health Insurance
      beneficiaries in a rural Japanese community. Their physical function was examined
      by the Medical Outcomes Study questionnaire at the end of 1994; medical care and
      its costs were then monitored for 1 year. SETTING AND PARTICIPANTS: Participants
      were the 49,364 subjects, aged 40 to 79 years, who were beneficiaries of National
      Health Insurance and lived in the catchment area of Ohsaki Public Health Center,
      Miyagi, Japan. The subjects were mainly farmers, self-employed persons,
      housewives, or pensioners. MEASUREMENTS: Medical care utilization (number of
      outpatient visits and days of inpatient care) and the costs for each subject were
      obtained from National Health Insurance Claim History files. These measurements
      were collected from January to December 1995, and the relationship between
      physical functioning levels and medical costs was analyzed. RESULTS: The medical
      costs per capita increased with poorer physical function. Medical costs among
      those with limitations in performing self-care increased by 4 times in men and 3
      times in women compared with those with no functional limitation. In this cohort,
      the 4.3% of the subjects who were dependent in self-care used 15% of the total
      inpatient days and 10% of the total medical costs. CONCLUSION: Treatment of
      patients with disability requires a huge amount of medical resources. There is an
      urgent need for cost-effective intervention programs for disability prevention,
      which could be offset against the cost for treating the disabled.

PMID- 10203125
TI  - Recruitment of older adults for a randomized, controlled trial of exercise advice
      in a general practice setting.
AB  - OBJECTIVES: The success of any clinical trial depends strongly on recruiting
      enough participants in a reasonable time period. This paper aims to identify the
      obstacles, as well as the successful aspects, of recruiting of older participants
      into an exercise study. DESIGN: This describes the recruitment of 299 older
      adults into a randomized, controlled trial of exercise advice in a general
      practice setting. Letters of invitation were sent from two general practices
      inviting the patients to attend a 15-minute screening appointment. Patients
      considered eligible for enrollment were then scheduled for a baseline appointment
      and randomized into the trial. SETTING: Two general practices in Adelaide, South
      Australia. PARTICIPANTS: Healthy, sedentary, community-dwelling patients aged 60
      years or older. RESULTS: A total of 2878 letters of invitation were sent, and 913
      patients attended a screening appointment. Of these, 351 (38.4%) were initially
      eligible, with one-third excluded because they were already too physically
      active. Two hundred ninety-nine participants, approximately 1 of every 10
      patients sent letters, were enrolled in the project at the end of a 15-week
      period. DISCUSSION: A general practice approach was effective in recruiting 299
      older adults to an exercise project within an acceptable time frame. Factors
      promoting the success of recruitment through general practice included choosing
      large, well established practices, computerized age-sex registers, and placing
      minimal demands on the general practitioners and practice staff. A continuing
      problem with recruiting participants for a project involving exercise is that the
      volunteer population tends to be healthy and interested in physical activity.

PMID- 10203126
TI  - Alzheimer's disease symptom severity in blacks and whites.
AB  - OBJECTIVE: In order to determine whether there are racial differences in
      Alzheimer's Disease (AD) symptom severity and vascular comorbidities, we compared
      African-American (black) and Caucasian (white) patients with AD from similar
      socioeconomic backgrounds at the time the disease was first recognized. DESIGN:
      Cross-sectional observational study from a population-based dementia registry.
      PARTICIPANTS: Patients were enrolled from an HMO base population of 23,000
      persons more than age 60 in Seattle, Washington. This study examines 453 subjects
      with probable AD (38 blacks (mean age 76.5, SD 6.4), and 415 whites (mean age
      79.7, SD 6.7)). MEASUREMENTS: Measured were patient demographics, age at onset of
      AD, AD symptom duration, Mini-Mental State Exam (MMSE) score, Blessed Dementia
      Rating Scale, presence of psychiatric symptoms, and vascular comorbidities.
      RESULTS: Blacks had significantly lower mean cognitive scores (MMSE = 17.2, SD
      5.6) compared with whites (MMSE = 20.2, SD 5.2, unpaired t test P < .01). The
      significant racial difference in MMSE scores persisted after controlling for
      education, duration of AD symptoms, age, and ADL impairment. Blacks and whites
      did not differ significantly regarding gender distribution, education level,
      income, or percent with early age of onset of AD. No statistically significant
      race-related differences were found in impairments in activities of daily living
      or symptoms of paranoia, hallucinations, or agitation. Blacks had significantly
      higher rates of hypertension (56%) compared with whites (34%) (Fisher's exact
      test, P = .013), but the rates of stroke and ischemic heart disease were similar.
      CONCLUSIONS: Despite uniform detection methods and controlling for reported
      duration of dementia symptoms, measured cognitive impairment is significantly
      more severe when AD is recognized in blacks compared with whites. The
      significantly higher prevalence of hypertension among black AD cases was not
      associated with excess cerebrovascular disease comorbidity. This study highlights
      a need for normative measurements of cognitive function in minority AD groups in
      order to distinguish differential cognitive symptom severity from possible
      measurement bias.

PMID- 10203128
TI  - Nursing home staff as research partners.

PMID- 10203127
TI  - The General Medical Health Rating: a bedside global rating of medical comorbidity
      in patients with dementia.
AB  - OBJECTIVE: Dementia is a serious public health problem. General medical
      comorbidity is common in dementia patients and critical to their care. However,
      little is known about medical comorbidity in these patients, and there are no
      straightforward bedside global rating scales for the seriousness of comorbid
      medical illness. This paper describes the development and measurement properties
      of the General Medical Health Rating (GHMR), a rapid global rating scale of
      medical comorbidity in dementia patients. DESIGN: Interrater reliability,
      concurrent validity, and predictive validity of the GMHR are reported. SETTING:
      An outpatient dementia clinic, assisted living, and nursing home. PARTICIPANTS: A
      total of 819 consecutive dementia clinic outpatients and 180 consecutive
      admissions to Copper Ridge, a long-term care residence for people with dementia,
      were included in the study. RESULTS: GMHR was found to be highly reliable
      (weighted kappa = .91). Across all stages and types of dementia, GMHR ratings
      were correlated with number of comorbid medical conditions, number of medications
      being taken for comorbid conditions, and with activity of daily living
      impairment, even after adjustment for severity of dementia. GMHR ratings were
      also a strong predictor of falls and of mortality in long-term care residents
      after adjustment for age and severity of dementia. CONCLUSION: GMHR is a
      reliable, valid, global bedside measure of severity of general medical
      comorbidity for patients with dementia that can be used for clinical and research
      purposes.

PMID- 10203129
TI  - Defining geriatric medicine in the managed care era.

PMID- 10203130
TI  - Cancer in the oldest old.

PMID- 10203131
TI  - The ten-year experience of the Palo Alto Veterans Affairs Home-Based Primary Care
      Program.

PMID- 10203132
TI  - The timed "Up & Go" test and manual button score are useful predictors of
      functional decline in basic and instrumental ADL in community-dwelling older
      people.

PMID- 10203133
TI  - Contribution of reflection of pressure wave on central systolic blood pressure in
      older hypertensive patients.

PMID- 10203134
TI  - Brain waves and brain wiring: the role of endogenous and sensory-driven neural
      activity in development.
AB  - Neural activity is critical for sculpting the intricate circuits of the nervous
      system from initially imprecise neuronal connections. Disrupting the formation of
      these precise circuits may underlie many common neurodevelopmental disorders,
      ranging from subtle learning disorders to pervasive developmental delay. The
      necessity for sensory-driven activity has been widely recognized as crucial for
      infant brain development. Recent experiments in neurobiology now point to a
      similar requirement for endogenous neural activity generated by the nervous
      system itself before sensory input is available. Here we use the formation of
      precise neural circuits in the visual system to illustrate the principles of
      activity-dependent development. Competition between the projections from lateral
      geniculate nucleus neurons that receive sensory input from the two eyes shapes
      eye-specific connections from an initially diffuse projection into ocular
      dominance columns. When the competition is altered during a critical period for
      these changes, by depriving one eye of vision, the normal ocular dominance column
      pattern is disrupted. Before ocular dominance column formation, the highly
      ordered projection from retina to lateral geniculate nucleus develops. These
      connections form before the retina can respond to light, but at a time when
      retinal ganglion cells spontaneously generate highly correlated bursts of action
      potentials. Blockade of this endogenous activity, or biasing the competition in
      favor of one eye, results in a severe disruption of the pattern of
      retinogeniculate connections. Similar spontaneous, correlated activity has been
      identified in many locations in the developing central nervous system and is
      likely to be used during the formation of precise connections in many other
      neural systems. Understanding the processes of activity-dependent development
      could revolutionize our ability to identify, prevent, and treat developmental
      disorders resulting from disruptions of neural activity that interfere with the
      formation of precise neural circuits.

PMID- 10203135
TI  - Mannose-binding protein B allele confers protection against tuberculous
      meningitis.
AB  - Inhalation is the principal mode of entry for Mycobacterium tuberculosis in
      humans. Primary infection is usually restricted to the lungs and contiguous lymph
      nodes. In a subset of infected individuals, predominantly children, the infection
      is spread hematogenously to the meninges. The host factors that influence the
      development of tuberculous meningitis have not been well elucidated. The mannose
      binding protein (MBP), a serum protein, is considered as an "ante-antibody." MBP
      has been shown to bind mycobacteria and acts as an opsonin in vitro. Although MBP
      plays a role in first-line host defense, it may under certain circumstances be
      deleterious to the host. In tuberculosis (TB), MBP may assist the spread of this
      intracellular pathogen. Therefore, we hypothesized that MBP genotypes that result
      in a phenotype of low MBP levels might be protective. We studied a well-defined
      South African population in which TB has reached epidemic levels. We found that
      the MBP B allele (G54D), which disrupts the collagen region of the protein and
      results in low MBP levels, was found in 22 of 79 (28%) of the TB-negative
      controls from the same community, compared with 12 of 91 (13%) of the patients
      with pulmonary TB (p < 0.017), and 5 of 64 (8%) of patients with tuberculous
      meningitis (p < 0.002). In addition, we found significantly lower serum MBP
      concentrations in TB-negative controls compared with postacute phase, fully
      recovered TB patients (p < 0.004). These findings suggest that the MBP B allele
      affords protection against tuberculous meningitis.

PMID- 10203136
TI  - Reversal of hypopigmentation in phenylketonuria mice by adenovirus-mediated gene
      transfer.
AB  - Phenylketonuria (PKU) is caused by deficiency of phenylalanine hydroxylase (PAH)
      in the liver. Patients with PKU show increased L-phenylalanine in blood, which
      leads to mental retardation and hypopigmentation of skin and hair. As a step
      toward gene therapy for PKU, we constructed a replication-defective, E1/E3
      deleted recombinant adenovirus harboring human PAH cDNA under the control of a
      potent CAG promoter. When a solution containing 1.2 x 10(9) plaque-forming units
      of the recombinant adenovirus was infused into tail veins of PKU model mice
      (Pah(enu2)), predominant expression of PAH activity was observed in the liver.
      The gene transfer normalized the serum phenylalanine level within 24 h. However,
      it also provoked a profound host immune response against the recombinant virus;
      as a consequence, the biochemical changes lasted for only 10 d and rechallenge
      with the virus failed to reduce the serum phenylalanine concentration.
      Administration of an immunosuppressant, FK506, to mice successfully blocked the
      host immune response, prolonged the duration of gene expression to more than 35
      d, and allowed repeated gene delivery. We noted a change in coat pigmentation
      from grayish to black after gene delivery. The current study is the first to
      demonstrate the reversal of hypopigmentation, one of the major clinical
      phenotypes of PKU in mice as well as in humans, by adenovirus-mediated gene
      transfer, suggesting the feasibility of gene therapy for PKU.

PMID- 10203137
TI  - Genotype and intellectual phenotype in untreated phenylketonuria patients.
AB  - Previous studies have shown that genotype correlates with biochemical phenotype
      in treated phenylketonuria. If there is a strong correlation between genotype and
      intellectual phenotype of untreated patients, it would be possible to determine
      which individuals would have normal intelligence without treatment. In this
      study, 42 families with untreated phenylketonuria were analyzed to examine
      whether there was an association between genotype and untreated intellectual
      phenotype. Previously 12 of the 42 families were genotyped; now the genotyping of
      these patients is almost complete (40/42), a more thorough investigation was
      possible. Although the predicted phenylalanine hydroxylase (PAH) enzyme activity,
      based on genotype, showed an association with the patients' intellectual
      phenotype, the extensive overlap between the groups means the association is of
      little clinical value. Unrelated individuals with the same genotype and also
      siblings were found to have very different intellectual phenotypes. These
      phenotypic differences could not be explained by a difference in diet; therefore,
      we propose that another gene or genes may be modifying the intellectual phenotype
      of untreated patients. A preliminary search for possible modifying genes was
      performed. The possibility that a modifying gene was linked to the PAH gene on
      chromosome 12 was investigated using markers closely linked to the gene; however,
      no evidence for a modifying gene close to the PAH gene was found. Tyrosine
      hydroxylase was chosen as a candidate gene, because it can perform the same
      reaction as PAH. Using a common polymorphism within the gene, we found that this
      gene did not cause the discordant results and thus, did not modify the PAH
      phenotype.

PMID- 10203138
TI  - Synergistic effects of cAMP- and calcium-mediated amylase secretion in isolated
      pancreatic acini from cystic fibrosis mice.
AB  - We evaluated pancreatic enzyme secretory response to secretagogues (cAMP- and
      Ca2+-mediating) involved in exocytosis and in chloride channel activation in an
      exon 10 knockout cystic fibrosis (CF) mouse model. Experiments were performed in
      isolated pancreatic acini from liquid-fed Cftr-/- mice (5-6 wk of age) and age
      matched Cftr+/+ controls fed a solid or liquid diet. BrcAMP and forskolin alone
      induced higher amylase secretion (% initial amylase content) in the Cftr+/+ acini
      than carbachol (p < 0.05). Carbachol and BrcAMP or BrcAMP and forskolin, given in
      combination, produced additive effects on enzyme secretion in the Cftr+/+ acini.
      Ca2+- and cAMP-mediated amylase secretion in isolated pancreatic acini from the
      Cftr-/- mice was no different to that observed in the age- and diet-matched
      Cftr+/+ animals. However, Cftr-/- pancreatic acini showed a significantly greater
      amylase response to the combination of BrcAMP and carbachol than the sum of the
      individual responses in separate experiments (p < 0.05). The amylase response was
      not different in acini from solid-fed or liquid-fed Cftr+/+ controls. In summary,
      this study suggests that cystic fibrosis transmembrane conductance regulator is
      not essential for enzyme secretion as evidenced by no reduction in cAMP-mediated
      amylase secretion in Cftr-/- mice. The results in Cftr+/+ acini suggest
      pancreatic enzyme secretion is mediated via multiple intracellular pathways
      acting in parallel and probably converge at a distal step in the secretory
      process. However, Cftr-/- pancreatic acini exhibited a synergistic secretory
      response following stimulation by BrcAMP plus carbachol. The enhanced secretory
      response may partially contribute to the development of pancreatic dysfunction in
      CF patients by facilitating occlusion of digestive enzymes in the secretory
      canaliculus of the pancreatic acini.

PMID- 10203139
TI  - 17Beta-estradiol and progesterone supplementation in extremely low-birth-weight
      infants.
AB  - During pregnancy, 17beta-estradiol (E2) and progesterone (P) plasma
      concentrations increase up to 100-fold. The fetus is exposed to these increasing
      amounts of E2 and P. Within 1 d after delivery, E2 and P concentrations fall to
      nonpregnancy concentrations in the mother and the infant. Extremely premature
      infants are cut off from the placental supply of E2 and P at a very early
      developmental stage, and therefore they suffer from this deprivation for a longer
      period than infants born at term. Nothing is known about the consequences of this
      deprivation. The purpose of this study was to investigate how intrauterine
      concentrations of E2 and P could be maintained after birth. In 13 infants with a
      median gestational age of 26.4 wk (24.1-28.7), a phospholipid-stabilized soybean
      oil emulsion available for parenteral nutrition that contains different amounts
      of E2 and P was continuously administered, starting within the first postnatal
      hours. The supplementation was continued as long as venous access was indicated
      but not longer than 6 wk (median 20 d, 12-44). To maintain intrauterine plasma
      concentrations of 2000-6000 pg/mL E2 and 300-600 ng/mL P, 2.30 mg x kg(-1) x d(
      1) E2 (1.13-3.42 mg x kg(-1) x d(-1)) and 21.20 mg x kg(-1) x d(-1) P (11.23
      27.36 mg x kg(-1) x d(-1)) were needed. We conclude that supplementation of E2
      and P to maintain intrauterine concentrations in extremely premature infants is
      possible intravenously. The infants in this study are enrolled in a randomized,
      controlled pilot study to evaluate the potential benefits of E2 and P
      supplementation.

PMID- 10203140
TI  - Human fetal and maternal noradrenaline responses to invasive procedures.
AB  - Fetal and maternal plasma noradrenaline responses to invasive procedures were
      determined in pregnancies of 18 to 37 wk gestation. Fetal umbilical venous blood
      sampling was performed either from the placental cord insertion, which is not
      innervated, or the intrahepatic vein, which is innervated, and thus may be more
      stressful for the fetus. Samples from diagnostic procedures, as well as from
      transfusion procedures, were compared between the two sites. Fetal plasma levels
      were significantly elevated in blood samples obtained from the intrahepatic vein
      compared with those from the placental cord insertion during diagnostic
      procedures [p < 0.05, geometric means and 95% confidence intervals (CI) were 0.67
      nmol/L (0.43-1.04) and 0.36 nmol/L (0.25-0.54), respectively]. Plasma levels in
      samples taken before transfusion from the intrahepatic vein were also
      significantly higher than those from the placental cord insertion. After
      transfusion, there was a significant rise in fetal plasma noradrenaline levels at
      both sites; however, after transfusion through the intrahepatic vein, the rise
      was substantially greater than after transfusion through the placental cord
      insertion (p < 0.05, change, mean deltaNA, and 95% CI were 0.67 (0.37-1.22), and
      0.20 (0.12-0.33), respectively). The deltaNA was significantly associated with
      the duration of the stimulus (the time the needle remained in situ) (p = 0.05,
      adjusted R2 = 0.48) and with gestational age. Maternal levels rose substantially
      and equally after transfusions at either site (mean deltaNA and 95% CI, 6.46
      nmol/L, 1.74 to 11.18 and 9.49 nmol/L, 6.24 to 12.75 for the intrahepatic vein
      and placental cord insertion groups, respectively). There was no significant
      correlation between baseline fetal and maternal levels (r = 0.08, n = 41) or
      between deltaNA pre- and posttransfusion maternal and fetal values in either
      group. These results indicate that the fetus is capable of mounting an
      independent noradrenaline stress response to a needle transgressing its trunk
      from 18 wk gestation. The effect was observable in samples taken at a mean of 5.6
      min after needling. The lack of correlation between maternal and fetal levels
      suggests that virtually no noradrenaline crosses the placenta directly, and that
      the observed fetal responses are not due to direct transport from the mother.

PMID- 10203141
TI  - Chemokine and inflammatory cell response to hypoxia-ischemia in immature rats.
AB  - Hypoxia-ischemia induces an inflammatory response in the immature central nervous
      system that may be important for development of brain injury. Recent data
      implicate that chemoattractant cytokines, chemokines, are involved in the
      recruitment of immune cells. The aim was to study alpha- and beta-chemokines in
      relation to the temporal activation of inflammatory cells after hypoxia-ischemia
      in immature rats. Hypoxia-ischemia was induced in 7-day-old rats (left carotid
      artery occlusion + 7.7% oxygen). The pups were decapitated at different times
      after the insult. Immunohistochemistry was used for evaluation of the
      inflammatory cell response and RT-PCR to analyze the cytokine mRNA and chemokine
      mRNA expression. A distinct interleukin-1beta and tumor necrosis factor-alpha
      cytokine expression was found 0-24 h after hypoxia-ischemia that was accompanied
      by induction of alpha-chemokines (growth related gene and macrophage inflammatory
      protein-2). In the next phase, the beta2-integrin expression was increased (12 h
      and onward) and neutrophils transiently invaded the vessels and tissue in the
      infarct region. The mRNA induction for the beta-chemokines macrophage
      inflammatory protein-1alpha, macrophage inflammatory protein-1beta, and RANTES
      preceded the expression of markers for lymphocytes [cluster of differentiation
      (CD)4, CD8], microglia/macrophages (MHC I), and natural killer cells in the
      infarct area. The activation of microglia/macrophages, CD4 lymphocytes, and
      astroglia persisted up to at least 42 d of postnatal age implicating a chronic
      component of immunoinflammatory activation. The expression of mRNA for alpha- and
      beta-chemokines preceded the appearance of immune cells suggesting that these
      molecules may have a role in the inflammatory response to insults in the immature
      central nervous system.

PMID- 10203142
TI  - The role of low molecular weight hyaluronic acid contained in Wharton's jelly in
      necrotizing funisitis.
AB  - The purpose of this research was to study the changes in the molecular weight of
      hyaluronic acid in Wharton's jelly altered by necrotizing funisitis. Umbilical
      cords were collected at delivery from 20 newborns without funisitis, 6 newborns
      with acute funisitis, and 4 newborns with necrotizing funisitis. Agarose gel
      electrophoresis of Wharton's jelly was performed to analyze the molecular weight
      of hyaluronic acid (HA). We also investigated the effects of low or high
      molecular weight HA on the production of interleukin-8 in human umbilical
      fibroblasts. In Wharton's jelly without funisitis, HA was 1150 +/- 280 kD in
      preterm newborns, regardless of gestational week at birth, and that in full-term
      newborns was 1100 +/- 200 kD. When acute funisitis was present, HA was 700 +/-
      250 kD, and when necrotizing funisitis was present, HA was 520 +/- 100 kD. The
      molecular weight of HA was significantly below normal in newborns with
      necrotizing funisitis. Low molecular weight HA was associated with increased
      levels of IL-8 in the supernatant of cultured human umbilical fibroblasts in a
      time- and dose-dependent manner. High molecular weight HA did not induce the
      production of IL-8 in the same cells. Low molecular weight HA has a potent
      inflammatory action. The conversion from high to low molecular weight HA in
      Wharton's jelly may be important in the pathophysiology of necrotizing funisitis.

PMID- 10203143
TI  - Heart rate modifications related to spontaneous body movements in sleeping
      premature and full-term newborns.
AB  - Heart rate (HR) acceleration is an essential mechanism for adaptation to changes
      in hemodynamic and energetic needs resulting from body movements. To evaluate age
      related development of coupling between spontaneous movement and HR changes, we
      performed polysomnographic recordings in 20 clinically and neurologically normal
      newborns including 10 premature (31- to 36-wk gestational age, wGA) and 10 full
      term (38- to 41-wk gestational age) infants. Recordings were sampled at 286 Hz
      and processed using a signal-to-noise ratio algorithm for QRS complex detection.
      Movements were automatically detected and the logical signal obtained was sampled
      at QRS fiducial points and written in the attributes of each QRS. The study
      included the 402 movements that were less than 30 s in duration and were neither
      preceded nor followed by another movement or by a respiratory event (pause,
      sigh). The amplitude of movement-induced HR acceleration was significantly lower
      in premature compared with full-term newborns (p < 0.01). This difference
      persisted when the other factors influencing the HR response (basal HR, movement
      duration, and amplitude) were taken into consideration. Our data identify HR
      acceleration induced by spontaneous body movements as a fundamental reflex
      response that develops with gestational age from premature to full-term newborns.

PMID- 10203144
TI  - The developmental character of cardiac autonomic responses to an acute noxious
      event in 4- and 8-month-old healthy infants.
AB  - Heart rate (HR) has been widely studied as a measure of an individual's response
      to painful stimuli. It remains unclear whether changes in mean HR or the
      variability of HR are specifically related to the noxious stimulus (i.e. pain).
      Neither is it well understood how such changes reflect underlying neurologic
      control mechanisms that produce these responses, or how these mechanisms change
      during the first year of life. To study the changes in cardiac autonomic
      modulation that occur with acute pain and with age during early infancy, the
      relationship between respiratory activity and short-term variations of HR (i.e.
      respiratory sinus arrhythmia) was quantified in a longitudinal study of term born
      healthy infants who underwent a finger lance blood collection at 4 months of age
      (n = 24) and again at 8 months of age (n = 20). Quantitative respiratory activity
      and HR were obtained during baseline, lance, and recovery periods. Time and
      frequency domain analyses from 2.2-min epochs of data yielded mean values,
      spectral measures of low (0.04-0.15 Hz) and high (0.15-0.80 Hz) frequency power
      (LF and HF), and the LF/HF ratio. To determine sympathetic and parasympathetic
      cardiac activity, the transfer relation between respiration and HR was used. At
      both 4 and 8 months, mean HR increased significantly with the noxious event (p >
      0.01). There were age-related differences in the pattern of LF, HF, and LF/HF
      ratio changes. Although these parameters all decreased (p > 0.01) at 4 months, LF
      and LF/HF increased at 8 months and at 8 months HF remained stable in response to
      the noxious stimulus. Transfer gain changes with the lance demonstrated a change
      from predominant vagal baseline to a sympathetic condition at both ages. The
      primary finding of this study is that a response to an acute noxious stimulus
      appears to produce an increase in respiratory-related sympathetic HR control and
      a significant decrease in respiratory-related parasympathetic control at both 4
      and 8 months. Furthermore, with increasing age, the sympathetic and
      parasympathetic changes appear to be less intense, but more sustained.

PMID- 10203145
TI  - Additive effect of tumor necrosis factor-alpha and endotoxin on bilirubin
      cytotoxicity.
AB  - Clinical observations suggest that sepsis may enhance the risk of kernicterus.
      This study investigated the combined effects of bilirubin, endotoxin, and tumor
      necrosis factor-alpha (TNF-alpha), which simulate sepsis in a jaundiced mouse
      fibroblast cell line. The horseradish peroxidase oxidation method was applied for
      bilirubin-albumin titration studies to test the effect of endotoxin and TNF-alpha
      on bilirubin-albumin binding. A modified 3-(4, 5-dimethylthiazol-2-yl)-2,5
      diphenyl-tetrazolium bromide method was used to study cytotoxicity. Bilirubin
      caused cytotoxicity in a dose-dependent manner in the cultured mouse fibroblasts.
      Such an effect was significantly amplified by TNF-alpha and endotoxin. TNF-alpha
      and endotoxin had no effect on the bilirubin-albumin titration curves. Our
      results have shown that TNF-alpha and endotoxin increase the cytotoxicity of
      bilirubin. These findings provide supportive evidence that sepsis would increase
      the risk of tissue damage by bilirubin.

PMID- 10203146
TI  - Effects of the respiratory stimulant almitrine on breathing and FOS expression in
      the brain of fetal and newborn sheep.
AB  - Almitrine is a piperazine derivative known to stimulate breathing in the adult
      but cause apnea in fetal sheep. In fetal sheep (127-133 d gestation; term = 147
      d) we confirmed this finding, but found that almitrine (4 mg/kg, i.v. or intra
      arterial) had a biphasic effect, briefly stimulating and then suppressing
      breathing movements for at least 3 h. In 2- to 3-d-old (n = 4) and 7- to 14-d-old
      (n = 4) lambs almitrine increased both tidal volume and breath frequency,
      increased arterial partial pressure of oxygen and pH, and decreased partial
      pressure of carbon dioxide. The changes of tidal volume, partial pressure of
      oxygen and partial pressure of carbon dioxide were less in the 2- to 3-d-old
      compared with the 7- to 14-d-old lambs. The distribution of the nuclear
      phosphoprotein FOS, a marker of neuronal activation was examined in fetal and
      newborn brains. FOS protein was increased in cardiorespiratory areas of the
      medulla and pons, in the periaqueductal region of the midbrain, and in the
      supraoptic and paraventricular regions of the hypothalamus. In the pons, FOS
      protein was increased in the medial parabrachial and subcoeruleus nuclei in the
      fetuses but not in the 2- to 3- or 7- to 14-d-old lambs. These observations are
      similar to those reported for hypoxia, and consistent with the hypothesis that
      both almitrine and hypoxia inhibit fetal breathing movements by an action on a
      select group of pontine neurons. Whether these neurons respond directly to these
      stimuli or receive input from the other centers is yet to be elucidated. The
      mechanisms that change the almitrine (and hypoxia) response from inhibition to
      excitation at birth have not been identified, but may be important in preventing
      apnea in the newborn.

PMID- 10203147
TI  - Relative osteopenia after treatment for acute lymphoblastic leukemia.
AB  - Osteoporosis in adult life is associated with a significant morbidity and may be
      predisposed to by osteopenia and failure to reach peak bone mass in childhood.
      Children treated for acute lymphoblastic leukemia (ALL) may be at risk of
      osteopenia as a result of previous therapy or as a consequence of the disease
      process itself. Dual energy x-ray absorptiometry measurements of bone mineral
      content (BMC) for the whole body and at the lumbar spine and hip were taken in 35
      (14 male) long-term survivors of ALL and compared with results in 20 (10 male)
      survivors of other malignancies and 31 (17 male) healthy sibling controls. The
      measured BMC was expressed as a percentage of a predicted value derived from the
      control group and based on the variables that had influence upon it. BMC (%) was
      reduced at the spine in the ALL group compared with controls [92.4 (8.0)% versus
      100.4 (9.7)%, respectively; p < 0.005] and at the hip compared with both other
      malignancies and controls [89.0 (11.5)% versus 96.1 (11.7)% and 100.4 (9.2)%,
      respectively; p < 0.0005]. Increasing length of time off therapy was associated
      with a significant increase in %BMC at both the spine and the hip. For the spine,
      this association was significantly different between the ALL group and other
      malignancies, suggesting that any gain in %BMC after therapy was slower in
      children treated for ALL. Both exercise capacity and levels of physical activity
      were correlated with %BMC at the hip (r = 0.44, p < 0.001 and r = 0.29, p < 0.01,
      respectively). Previous exposure to methotrexate, ifosfamide, and bleomycin was
      associated with a reduction in %BMC at the spine. Exposure to 6-mercaptopurine
      and cisplatin was associated with a reduction at the hip. In conclusion, children
      treated for ALL are osteopenic. The mechanism is probably multifactorial but is
      partially related to previous chemotherapy, limited exercise capacity, and
      relative physical inactivity.

PMID- 10203148
TI  - Myc oncogene expression and nude mouse tumorigenicity and metastasis formation
      are higher in alveolar than embryonal rhabdomyosarcoma cell lines.
AB  - Accumulated clinical evidence suggests that alveolar rhabdomyosarcoma (ARMS) is
      more aggressive than embryonal rhabdomyosarcoma (ERMS). Here, we study six
      childhood rhabdomyosarcoma cell lines, three ERMS and three ARMS. We have assayed
      the ability of the tumor cells to grow in culture and in nude mice as well as
      their propensity for pulmonary metastasis formation by tail vein injection. We
      also compared levels of c- and N-myc oncogene expression and DNA copy number. We
      find no correlation of histologic tumor type (i.e. ERMS versus ARMS) with growth
      rate in culture, but we do find suggestive correlations of histologic type with
      tumorigenicity (mean tumor diameter in millimeters at 6 wk: ARMS 30, ERMS 10; p1
      = 0.1) and metastasis formation (ARMS 12, ERMS 0; p1 = 0.1). These properties
      also correlate with uniform greater overexpression of c-myc in ARMS (mean 39.3
      fold, range 16-83) compared with ERMS (mean 5.3, range 4-8) (p1 = 0.05, control
      fibroblasts = 1). Although c-myc was often amplified in vitro (four of six
      lines), there was no correlation with histologic type (2/3 ARMS, 2/3 ERMS). These
      data on rhabdomyosarcoma cell lines derived from verified ERMS and ARMS tumors
      support the impression from previous clinicopathologic observations that ARMS is
      a more malignant form of rhabdomyosarcoma than ERMS.

PMID- 10203149
TI  - Central motor reorganization in cerebral palsy patients with bilateral cerebral
      lesions.
AB  - Transcranial magnetic stimulation (TMS) has been used to describe cortical
      plasticity after unilateral cerebral lesions. The objective of this study was to
      find out whether cortical plasticity occurs after bilateral cerebral lesions. We
      investigated central motor reorganization for the arm and leg muscles in cerebral
      palsy (CP) patients with bilateral cerebral lesions using TMS. Seventeen patients
      (12 with spastic diplegia, 1 with spastic hemiplegia, and 4 with athetoid CP) and
      10 normal subjects, were studied. On CT/MRI, bilateral periventricular
      leukomalacia was observed in all spastic patients with preterm birth. In two
      normal subjects, motor responses were induced in the ipsilateral tibialis
      anterior, but no responses were induced in any normal subject in the ipsilateral
      abductor pollicis brevis (APB) or biceps brachii (BB). Ipsilateral responses were
      more common among CP patients, especially in TMS of the less damaged hemisphere
      in patients with marked asymmetries in brain damage: in 3 abductor pollicis
      brevis, in 6 BBs, and in 15 tibialis anteriors. The cortical mapping of the sites
      of highest excitability demonstrated that the abductor pollicis brevis and BB
      sites in CP patients were nearly identical to those of the normal subjects. In
      patients with spastic CP born prematurely, a significant lateral shift was found
      for the excitability sites for the tibialis anterior. No similar lateral shift
      was observed in the other CP patients. These findings suggest that ipsilateral
      motor pathways are reinforced in both spastic and athetoid CP patients, and that
      a lateral shift of the motor cortical area for the leg muscle may occur in
      spastic CP patients with preterm birth.

PMID- 10203150
TI  - Response of fetal rabbit ductus arteriosus to bradykinin: role of nitric oxide,
      prostaglandins, and bradykinin receptors.
AB  - Nitric oxide plays a major role in vascular tone control. Increased blood levels
      of bradykinin (BK), which stimulates nitric oxide biosynthesis, occur at birth.
      BK effects on ductus arteriosus (DA) tone were investigated in fetal rabbit under
      fetal (2.5% O2 "low PO2") and neonatal (30% O2 "high PO2") conditions using in
      vitro isometric tension studies. Intact and endothelium-denuded DA, contracted
      with norepinephrine (ED75-90), showed a biphasic response to BK, with relaxation
      at 10(-9) to 10(-7) M BK and contraction at 10(-6) to 10(-5) M BK. BK (10(-6) to
      10(-5) M) contracted intact DA from baseline tension, with greater contraction
      under high PO2. The B2-receptor antagonist D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]-BK (Hoe
      140, 10(-7) M) abolished relaxation, but not contraction, to BK in intact and
      denuded DA. The B1-receptor antagonist des-Arg9-[Leu5]-BK (10(-7) M) reduced BK
      induced contraction but not relaxation in intact DA only. Nitric oxide synthase
      inhibitors, N(omega)-nitro-L-arginine methyl ester (10(-4) M) and N(omega)
      monomethyl-L-arginine (10(-4) M) partially inhibited relaxation to BK in intact
      DA, with L-arginine (3 x 10(-4) M) reversing N(omega)-monomethyl-L-arginine
      inhibition. N(omega)-nitro-L-arginine methyl ester (10(-4) M) caused a small but
      significant inhibition of relaxation to BK in denuded DA. Indomethacin (2.8 x 10(
      6) M), a cyclooxygenase inhibitor, abolished relaxation but not contraction to BK
      in intact and denuded DA. BK-induced relaxation of the DA acts through B2
      receptors, releasing both nitric oxide and prostaglandins, whereas endothelial B1
      receptors may mediate contraction. BK action on isolated DA changes from
      relaxation to contraction as its concentration increases, with greater
      contraction at neonatal PO2. Thus increased BK levels at birth may aid functional
      closure of the DA.

PMID- 10203151
TI  - Acute intrauterine pulmonary hypertension impairs endothelium-dependent
      vasodilation in the ovine fetus.
AB  - To determine whether acute pulmonary hypertension in utero alters fetal pulmonary
      vascular reactivity, we compared pulmonary vasodilation with an endothelium
      dependent agonist, acetylcholine, with that of an endothelium-independent
      agonist, 8-bromo-guanosine 3',5'-cylic monophosphate. Acute pulmonary
      hypertension was produced in chronically prepared, late-gestation fetal lambs by
      3 repeated 30-minute partial occlusions of the ductus arteriosus (DA). The first
      DA compression increased LPA blood flow from 80 +/- 10 to 180 +/- 21 mL/min (p <
      0.01) and decreased pulmonary vascular resistance. In contrast, LPA blood flow
      did not change and pulmonary vascular resistance increased by 25% during the
      third period of DA compression. Pulmonary vasodilation during acetylcholine
      infusion after serial DA compressions was decreased in comparison with the
      acetylcholine-induced vasodilator response achieved during the baseline period
      (fall in pulmonary vascular resistance = -49 +/- 7% (baseline) versus -25 +/- 5%
      after repeated DA compressions; p < 0.05). In contrast, the vasodilator response
      to 8-bromo-guanosine 3',5'-cylic monophosphate remained intact. To determine
      whether decreased nitric oxide (NO) production may contribute to altered
      vasoreactivity after acute pulmonary hypertension, repeated DA compressions were
      performed after treatment with a nonspecific NO synthase inhibitor (nitro-L
      arginine). NO synthase inhibition blocked the pulmonary vasodilation during the
      first DA compression period, and repeated DA compressions after NO synthase
      inhibition did not further alter the hemodynamic response to DA compression.
      These findings support the hypothesis that brief hypertension due to DA
      compression impairs endothelium-dependent pulmonary vasodilation in the fetus,
      and that this may be due to decreased NO production.

PMID- 10203153
TI  - Increased tissue-type plasminogen activator antigen release is not accompanied by
      increased systemic fibrinolytic activity in severe neonatal respiratory distress
      syndrome.
AB  - Intravascular and intraalveolar fibrin depositions in preterm infants with severe
      respiratory distress syndrome (RDS) have been attributed to activation of
      clotting. We questioned whether in the face of activated clotting, fibrinolysis
      is sufficient in these infants. We found, in infants with severe RDS within 6 to
      12 h of birth, increased median thrombin-antithrombin III complex formation (11.1
      versus 1.3 ng/mL in the group with mild-to-moderate RDS, p < 0.001), indicating
      activation of clotting. Simultaneously, we found increased tissue-type
      plasminogen activator antigen (t-PA) release in plasma of these infants
      represented by increased median t-PA plasma concentrations (8.3 versus 2.5 ng/mL
      in the group with mild-to-moderate RDS, p < 0.01). This increased t-PA release
      was not accompanied with more plasminogen and antiplasmin consumption and with
      more fibrin and fibrinogen degradation than in the infants with mild-to-moderate
      RDS because plasma plasminogen and antiplasmin activity and total fibrin and
      fibrinogen degradation product concentrations were similar in both groups. We
      have found that activated clotting and t-PA plasma concentrations are positively
      correlated with arterial-to-alveolar oxygen tension ratio and ventilator
      efficiency index values. Plasminogen and antiplasmin activity, and total fibrin
      and fibrinogen degradation product concentrations were not correlated with these
      continuous measures of RDS severity. In neonatal RDS, clotting activity
      contributes to disease severity. Insufficient fibrinolysis likely facilitates the
      deleterious effects of activated clotting.

PMID- 10203152
TI  - Cerebrovascular responses to therapeutic dose of indomethacin in newborn pigs.
AB  - The aims of this study were 1) to compare the effects of low versus high doses of
      indomethacin on cerebral blood flow (CBF) responses to hypercapnia and 2) to
      investigate the effects of low-dose indomethacin on the cerebral vasculature
      during resting conditions and during vasodilator stimuli. In the first
      experiment, 27 piglets were randomized into three groups to receive 5 mg/kg
      indomethacin, 0.2 mg/kg indomethacin, or normal saline. Ninety minutes later, CBF
      was measured by radioactive microspheres at baseline, during hypercapnia [PaCO2 >
      or = 70 mm Hg (> or =9.3 kPa)] and normocapnia. Total CBF was comparable among
      the three groups at baseline. CBF increased during hypercapnia in all groups, but
      the hyperemic response was significantly attenuated in the high-dose indomethacin
      group compared with the saline group but not in the group treated with 0.2 mg/kg.
      CBF returned toward baseline during normocapnia in all piglets. In the second
      experiment, a closed cranial window was implanted over the parietal cortex of
      nine piglets. Cerebrovascular responses to hypercapnia and topical application of
      isoproterenol (10(-7) and 10(-6) M) and histamine (10(-6) and 10(-5) M) were
      investigated before and after administration of 0.2 mg/kg indomethacin. Within 10
      min of indomethacin administration, pial arteriolar diameters decreased from 72
      +/- 8 to 58 +/- 6 microm (p < 0.05), and 6-keto-PGF1alpha concentration decreased
      from 1440 +/- 250 to 570 +/- 30 pg/mL (p < 0.05). Two hours (138 +/- 21 min)
      later, pial arteriolar diameters had returned toward baseline values (65 +/- 5
      microm), whereas 6-keto-PGF1alpha values remained considerably lower than
      preindomethacin values (530 +/- 30 pg/mL). Cerebrovascular responses to dilator
      stimuli were preserved after 0.2 mg/kg indomethacin. We conclude that 0.2 mg/kg
      indomethacin does not markedly affect the cerebral hyperemic responses to
      hypercapnia in contrast with a very prominent inhibition by 5 mg/kg indomethacin.
      Also, although indomethacin at a low dose constricts pial arterioles transiently
      and attenuates cerebral prostanoid production, it does not inhibit the pial
      arteriolar responsiveness to prostanoid-associated dilator stimuli. This
      observation may be due to the permissive role that prostacyclin plays in cerebral
      vasodilatory responses to some vasogenic stimuli such as hypercapnia and
      histamine.

PMID- 10203154
TI  - Intestinal macromolecule absorption in the fetal pig after infusion of colostrum
      in utero.
AB  - The ability of the fetal pig intestine to absorb large proteins was investigated
      in utero. Six pregnant sows were anesthetized (Na pentobarbital) at 99-102 d of
      gestation (term = 115 +/- 2 d), and a catheter was inserted into the esophagus of
      two to three fetuses per sow. Via these catheters, sterile solutions (10.0 mL) of
      colostrum whey (CW, n = 5), milk whey (MW, n = 5), or amniotic fluid (AF, n = 4)
      were infused into the fetal pig stomachs every 6 h for 6-8 d starting on the day
      after surgery (d 0). Levels of IgG in the three fluids were 120, 0.5, and 0
      mg/mL, respectively. During the first 2-3 d of infusion, plasma IgG levels rose
      rapidly in the CW fetuses (to 7.5 +/- 0.8 mg/mL), whereas IgG remained absent in
      plasma from MW and AF fetuses. Absorption of a macromolecule marker, BSA, was
      also higher when the marker was given with CW rather than with MW or AF. However,
      when all three treatment groups were given CW + BSA on the last experimental day
      (d 6-8), the mean BSA increment in the CW group was only 5-8% of that in the AF
      group, with intermediate values for the MW group. Neither at the beginning nor at
      the end of the experiment was macromolecule uptake in individual CW fetuses
      correlated with their cortisol level in plasma. The prenatal pig intestine is
      similar to the neonatal pig intestine in that colostrum stimulates both the
      macromolecule absorption and the cessation of macromolecule uptake (intestinal
      closure). However, fetal pigs have a lower protein absorptive capacity and a
      longer preclosure period than newborn pigs; this may be related to an immature
      structure and function and a slow enterocyte proliferation rate in the prenatal
      pig intestine.

PMID- 10203155
TI  - Profile of urinary bile acids in infants and children: developmental pattern of
      excretion of unsaturated ketonic bile acids and 7beta-hydroxylated bile acids.
AB  - Unusual bile acids, such as unsaturated ketonic and 7beta-hydroxylated bile
      acids, have been detected in urine early in life. To elucidate the normal
      profiles of usual and unusual urinary bile acids in the neonatal and pediatric
      periods, we measured the concentrations of 28 kinds in urine from normal
      newborns, infants, and children by gas chromatography-mass spectrometry. The mean
      total bile acid/Cr ratio in 7-d-old infants was significantly higher than in
      subjects of other age groups (birth, 2-4 mo, 5-7 mo, 11-12 mo, 2-3 y, 9-14 y, and
      adult) (p < 0.05). Relatively large amounts of unusual bile acids were detected
      during infancy, especially during the period up to 1 mo of age. At that time,
      1beta,3alpha,7alpha,12alpha-tetrahydroxy-5bet a-cholan-24-oic, 7alpha, 12alpha
      dihydroxy-3-oxo-5beta-chol-1-en-24-oic, and 7alpha,12alpha-dihydroxy-3-oxo-4
      cholen-24-oic acids were predominant among the unusual urinary bile acids
      present. Moreover, the levels of 3alpha,7beta,12alpha-trihydroxy-5beta-cholan+ ++
      24-oic acid increased significantly after 2-4 mo of age. These results indicate
      that bile acid synthesis and metabolism in the liver of developing infants are
      significantly different from that occurring in the liver of adults. Significant
      amounts of urinary isomerized 7beta-hydroxylated bile acids were detected after
      late infancy, probably because of changes in the intestinal bacterial flora
      response to a change in nutrition. We describe, for the first time, evidence of
      the epimerization of the 7alpha-hydroxyl group of cholic acid, which may be
      unique to human development.

PMID- 10203156
TI  - Adenoid cystic carcinoma of the maxillary antrum.
AB  - PURPOSE: To investigate characteristic clinical features and outcome for patients
      with adenoid cystic carcinoma (ACC) of the maxillary antrum. PATIENTS AND
      METHODS: Twenty-two patients with ACC of the maxillary antrum were initially
      treated with surgery alone (3 patients), radiation alone (9 patients), or a
      combination of surgery and radiation (10 patients). Salvage treatment for initial
      failure was individualized. Patterns of failure, survival, and prognostic factors
      were retrospectively analyzed. RESULTS: The most frequent site of failure was
      local recurrence at the primary site (72.7%). All patients treated with either
      surgery alone or radiation alone experienced one or more local recurrences,
      whereas patients who received planned combined surgery and radiation had a much
      lower local recurrence rate (40%). Neck node failure (4.6%) was an uncommon
      event, whereas distant metastases were clinically documented in seven patients
      (32%). Most of the treatment failures appeared within 5 years, but treatment
      failures after 5 years were not uncommon. The overall survival and disease-free
      survival rates at 10 years were 37.6% and 13.6%, respectively.
      Clinicopathological factors, such as location of primary tumor, tumor stage, and
      histological grade were of no value in predicting a favorable survival. The
      significant prognostic factors influencing 10-year survival were the pathological
      finding of perineural invasion and the initial mode of treatment. CONCLUSION: ACC
      of the maxillary antrum represented a unique natural history characterized by a
      more aggressive tumor behavior and an unfavorable prognosis. Combined surgery and
      radiotherapy is recommended for optimal local control and survival.

PMID- 10203157
TI  - Clinical, bacteriological, and histological study of adenoids in children.
AB  - PURPOSE: The adenoid has long been recognized as an important factor in the
      pathogenesis of otitis media with effusion (OME). However, there is still
      considerable debate concerning how the condition of the adenoid tissue is
      involved in the cause of OME. The purpose of this study is to investigate whether
      the adenoid is an active agent of OME. PATIENTS AND METHODS: One hundred forty
      six patients aged from 3 to 6 years who underwent adenoidectomy at Oita Medical
      University (Japan) were retrospectively compared with patients with and without
      OME regarding macroscopic size of the adenoid, adenoidal-nasopharyngeal ratio (AN
      ratio), incidence of sinusitis and nasal allergy, bacteriological examination of
      adenoid tissues, reticular formation of the epithelium, and the percent of
      ciliated epithelium. RESULTS: There was no significant difference in the size of
      adenoids. Haemophilus influenzae (HI) was cultured more frequently in adenoid
      specimens from patients with OME. A tendency toward increased stratified squamous
      epithelium and decreased ciliated epithelium was apparent in patients with OME.
      Reticular epithelium extension was greater in patients with than without OME.
      CONCLUSION: Adenoid inflammation is implicated in the pathogenesis of OME and the
      adenoids have an important role in the cause of OME by being a reservoir for HI.

PMID- 10203158
TI  - Nonrecurrent laryngeal nerves: anatomic considerations during thyroid and
      parathyroid surgery.
AB  - PURPOSE: In head and neck surgery, damage to the recurrent laryngeal nerve (RLN)
      during thyroid surgery is the most common iatrogenic cause of vocal cord
      paralysis. Identification of the RLNs and meticulous surgical technique can
      significantly decrease the incidence of this complication. Nonrecurrent RLNs
      (NRRLNs) are exceedingly rare. Surgeons need to be aware of their position to
      avoid damage to them. MATERIALS AND METHODS: A retrospective review of 513 RLN
      exposures over a 7-year period was performed. RESULTS: Two NRRLNs were
      encountered, for an incidence of 0.39%. CONCLUSION: NRRLNs are rare. Awareness of
      their existence will prevent the surgeon from accidentally severing one if it is
      encountered during routine thyroid or parathyroid surgery.

PMID- 10203159
TI  - Propofol versus isoflurane for endoscopic sinus surgery.
AB  - PURPOSE: A previous retrospective study reported that propofol anesthesia
      decreased bleeding during endoscopic sinus surgery compared with isoflurane. We
      performed a prospective study to compare the effects of propofol versus
      isoflurane on measured blood loss and the surgeon's subjective assessment of
      operating conditions during endoscopic sinus surgery. PATIENTS AND METHODS: After
      receiving institutional review board approval and written informed consent, 56
      patients undergoing endoscopic sinus surgery were randomly assigned to receive
      propofol (n = 30) or isoflurane (n = 26) supplemented with nitrous oxide-oxygen
      and alfentanil. Blood loss was calculated from the hemoglobin concentration in
      suction canisters. One surgeon, who was blinded to the anesthetic agent,
      performed every procedure and assessed bleeding as follows: 1, no bleeding; 2,
      modest bleeding; 3, bleeding interfering with operating conditions and cause for
      an agent switch; and 4, intolerable bleeding requiring a change in surgical plan.
      Results were compared in the two anesthetic groups using chi-squared test,
      unpaired t-test, Mann-Whitney Utest, and a permutation test. A P of .05 was
      considered significant. RESULTS: Mean bleeding scores were less over time (P =
      .02) with propofol anesthesia, particularly in surgery in the ethmoid and
      sphenoid sinuses (P = .03), and the proportion of patients with a mean score >2
      was less in the propofol group (30% v 54%; P = .033). Time until discharge to
      home or to a limited stay in a hospital bed was also less in the propofol group
      (183 v 243 minutes; P = .019). CONCLUSION: In our study, surgical blood loss was
      the same for both anesthetic agents overall, but propofol appeared to offer an
      advantage in terms of subjective improvement in operating conditions,
      particularly in the ethmoid and sphenoid sinuses.

PMID- 10203160
TI  - Genetic correlation in otosclerosis.
AB  - PURPOSE: The aim of this study was to determine the relationship of HLA typing in
      patients with otosclerosis. MATERIALS AND METHODS: We used a prospective study in
      which HLA typing of 100 surgically confirmed otosclerosis patients were compared
      with age and sex matched normal individuals. RESULTS: HLA-A3, HLA-A9, HLA-A11,
      and HLA-B13 were found to be significantly higher (P < .05, .01, and .01,
      respectively). HLA-A9 and HLA-A11 were found to be higher (P < .01) in patients
      with a positive family history, indicating genetic heterogenicity. CONCLUSIONS:
      Higher values of HLA-A9, HLA-11, and HLA-B13 in patients with otosclerosis
      compared with normal individuals strongly suggests a genetic, HLA-related
      component.

PMID- 10203161
TI  - Presentation and diagnosis of unilateral maxillary swelling in children.
AB  - Facial asymmetry secondary to pathologic processes involving the maxillary sinus
      and its surrounding structures presents a challenge for the clinician. An
      organized approach to evaluate these patients is essential in order to
      differentiate inflammatory sinus pathology from disease processes primarily
      involving the surrounding maxilla, parotid gland, orbital contents, and dental
      structures. In addition to a thorough history and physical examination,
      appropriate imaging studies must be obtained to localize the pathologic processes
      and develop a meaningful differential diagnosis. Once this is accomplished,
      specific treatment modalities can be developed. Representative cases will be
      presented to illustrate this organized approach to unilateral maxillary swelling,
      including soft tissue and osseous masses, fibro-osseous lesions, osseous cysts
      and inflammatory lesions.

PMID- 10203162
TI  - Angiography contrast-induced transient cortical blindness.

PMID- 10203163
TI  - Bilateral chronic maxillary sinusitis after the sinus-lift procedure.

PMID- 10203164
TI  - Angioedema presenting in the retropharyngeal space in an adult.
AB  - PURPOSE: Hereditary angioedema is a rare disorder of deficient or dysfunctional
      C1-esterase inhibitor and usually manifests as edema of the face, tongue,
      supraglottis, extremities, or gastrointestinal tract. We report the case of a 40
      year-old man with known hereditary angioedema who presented with a sore throat
      and a sensation of evolving airway obstruction. After a thorough search of the
      medical literature, we believe this to be the first reported case of angioedema
      manifesting in the retropharyngeal space. The pathophysiological factors of
      angioedema are discussed, along with its variable presentation and management
      issues. METHOD: Laryngoscopic examination was suggestive of posterior pharyngeal
      fullness; therefore, a computed tomographic scan of the neck was obtained, which
      showed a non-contrast-enhancing retropharyngeal edema from the base of the skull
      to below the level of the glottis. The patient had a history of multiple episodes
      of angioedema requiring hospitalization and three prior tracheotomies. RESULTS:
      Familiarity with the patient's history directed his rapid treatment course
      (including intravenous stanozolol, Solu-Medrol, and diphenhydramine), which
      significantly reduced his edema and avoided the need for tracheotomy. CONCLUSION:
      Hereditary angioedema may present in atypical locations, and expeditious
      treatment in a patient with a known history may avert the sequelae of evolving
      airway obstruction.

PMID- 10203165
TI  - Pneumatized inferior turbinate.

PMID- 10203166
TI  - How does molecular epidemiology help to understand malaria?

PMID- 10203167
TI  - Increased prevalence of malaria in HIV-infected pregnant women and its
      implications for malaria control.
AB  - OBJECTIVES: To examine in pregnant women the relationship between HIV infection
      and malaria prevalence and to determine, in relation to HIV infection, the
      effectiveness of sulphadoxine-pyrimethamine in clearing P. falciparum infection.
      METHOD: Descriptive cross-sectional analysis of P. falciparum prevalence in
      pregnant women at first antenatal visit and of women at delivery who had received
      two sulphadoxine-pyrimethamine treatments for malaria. HIV status was assessed in
      621 women who attended for antenatal care and for delivery at two rural hospitals
      in southern Malawi in 1993-94. Information was collected on maternal age, parity
      and gestational age. Prevalence of P. falciparum was measured at first antenatal
      visit and delivery. Women were given two routine treatment doses of sulphadoxine
      pyrimethamine (SP), at first antenatal visit and between 28 and 34 weeks
      gestation, conforming to Malawi government policy on antimalarial control during
      pregnancy. RESULTS: Prevalence of HIV infection was 25.6% and all infections were
      HIV type-1. In primigravidae malaria prevalence at recruitment was 56.3% in HIV
      infected and 36.5% in HIV-uninfected women (P=0.04). The corresponding figures
      for multigravidae were 23.8% and 11.0%, respectively (P<0.01). HIV-infected
      primigravidae had increased malaria prevalence at all gestational ages. Peak
      parasite prevalence occurred earlier in gestation in HIV-infected primigravidae
      (16-19 weeks if HIV-infected; 20-23 weeks if HIV-uninfected). The relative risk
      for parasitaemia in HIV-infected compared to HIV-uninfected women was
      significantly increased in three of five parity groups, including the two highest
      ones (parity>3), indicating parity-specific immunity to malaria was impaired.
      Malaria prevalence at delivery remained high in HIV-infected women despite prior
      routine treatment with sulphadoxine-pyrimethamine in pregnancy There was no
      significant difference in parasite prevalence at delivery between women who did
      or did not use sulphadoxine-pyrimethamine. CONCLUSIONS: HIV infection is
      associated with a significant increase in malaria prevalence in pregnant women of
      all parities with the effect apparent from early in gestation. Two treatment
      doses of sulphadoxine-pyrimethamine were inadequate to clear parasitaemia in many
      women by the time of delivery and this occurred independently of HIV status and
      despite high sensitivity to SP in this area. There is a need to undertake
      longitudinal studies to determine the incidence of P. falciparum infection in HIV
      infected and uninfected pregnant women and to reassess the frequency and timing
      of sulphadoxine-pyrimethamine treatment doses in these women. Late pregnancy re
      infections with P. falciparum probably explain the high parasite prevalence at
      delivery following sulphadoxine-pyrimethamine treatment at 28-34 weeks gestation.

PMID- 10203168
TI  - Bancroftian filariasis in an irrigation project community in southern Ghana.
AB  - An epidemiological study to document the endemicity and transmission
      characteristics of bancroftian filariasis was conducted in an irrigation project
      community in southern Ghana. In a 50% random sample of the population, the
      prevalence of microfilaraemia was 26.4% and the geometric mean microfilarial
      intensity among positives was 819 microfilariae/ml of blood. Hydrocoele was found
      in 13.8% of the males aged > or =18 years, and 1.4% of the residents examined,
      all females, had tymphoedema/elephantiasis. Detailed monitoring of the
      microfilarial intensity in 8 individuals over a 24-h period confirmed its
      nocturnal periodicity with a peak at approximately 0100 hours. The most important
      vector was Anopheles gambiae s.l., followed by An. funestus. The abundance of
      these mosquitoes and their relative importance as vectors varied considerably
      between the wet and the dry season. Opening of the irrigation canals late in the
      dry season resulted in a remarkable increase in the population of An. gambiae
      (8.3% of which carried infective filarial larvae) to levels comparable to those
      seen during the wet season, suggesting that the irrigation project is responsible
      for increased transmission of lymphatic filariasis in the community.

PMID- 10203169
TI  - Treatment costs and loss of work time to individuals with chronic lymphatic
      filariasis in rural communities in south India.
AB  - This year-round case-control study investigated treatment costs and work time
      loss to people affected by chronic lymphatic filariasis in two rural communities
      in south India. About three-quarters of the patients sought treatment for
      filariasis at least once and 52% of them paid for treatment, incurring a mean
      annual expenditure of Rs. 72 (US $2.1; range Rs. 0-1360 (US $39.0)). Doctor's
      fees and medicines constituted 57% and 23% of treatment costs. The proportion of
      people seeking treatment was smaller and treatment costs constituted a higher
      proportion of household income in lower income groups. Most patients did not
      leave work, but spent only 4.36+/-3.41 h per day on economic activity compared to
      5.25+/-3.52 h worked by controls; the mean difference of 0.89+/-4.20 h per day
      was highly significant (P<0.01). This loss of work time is perpetual, as chronic
      disease manifestations are mostly irreversible. An estimated 8% of potential male
      labour input is lost due to the disease. Regression analyses revealed that
      lymphatic filariasis has a significant effect on work time allotted to economic
      activity (P<0.05) but not on absenteeism from work (P>0.05). Female patients
      spent 0.31+/-1.42 h less on domestic activity compared to their matched controls
      (P<0.05). The results clearly show that the chronic form of lymphatic filariasis
      inflicts a considerable economic burden on affected individuals.

PMID- 10203170
TI  - Independent evaluation of onchocerciasis rapid assessment methods in Benue State,
      Nigeria.
AB  - OBJECTIVE: To evaluate the prevalence of palpable nodules or skin depigmentation
      as rapid indicators of onchocerciasis epidemicity in at-risk communities. METHOD:
      We examined data collected in Benue State on 11035 individuals in 32 villages to
      evaluate these rapid assessment methods. RESULTS: The prevalence of palpable
      nodules correlates more closely with microfilarial prevalence (r=0.68, P<0.001)
      and community microfilarial load (r=0.64, P<0.001) than the prevalences of skin
      depigmentation or other potential rapid indicators. The recommended cut-off value
      for palpable nodules of 20% or more in males aged >20 years had a sensitivity of
      94% and specificity of 50% compared to a cut-off of 40% or more for microfilarial
      prevalence in all ages. This would mean that in these 32 villages 17 of 18 would
      have been correctly identified for treatment, and a further 7 at lesser risk
      would have been targeted for treatment. CONCLUSIONS: Skin snipping and
      parasitological examination can be replaced by the simpler method of palpating
      onchocercal nodules to identify communities at serious risk of onchocerciasis.
      This has important operational benefits for onchocerciasis control programmes.

PMID- 10203171
TI  - Multi-centre evaluation of repeatability and reproducibility of the direct
      agglutination test for visceral leishmaniasis.
AB  - OBJECTIVE: To evaluate the repeatability and reproducibility of the serological
      direct agglutination test (DAT) for visceral leishmaniasis (VL) with aqueous
      antigen in a multi-centre study in VL-endemic areas in Sudan, Kenya and Nepal.
      METHODS: Repeatability within each centre and reproducibility between the
      centres' results and an external reference laboratory (Belgium) was assessed on
      1596 triplicate plain blood samples collected on filter paper. RESULTS: High
      kappa values (range 0.86-0.97) indicated excellent DAT repeatability within the
      centres. The means of the titre differences between the reference laboratory and
      the centres in Sudan, Kenya and Nepal (2.3, 2.4 and 1.1, respectively, all
      significantly different from 0) showed weak reproducibility across centres. 95%
      of the titre differences between the reference laboratory and the respective
      centres were accounted for by large intervals: 0.6-9 fold titre variation for
      Sudan, 0.7-8 fold for Kenya and 0.26-4 fold for Nepal. CONCLUSION: High
      repeatability of DAT confirms its potential, but reproducibility problems remain
      an obstacle to its routine use in the field. Reproducibility was hindered by
      alteration of the antigen through temperature and shaking, especially in Kenya
      and Sudan, and by nonstandardization of the test reading. DAT handling procedures
      and antigen quality must be carefully standardized and monitored when introducing
      this test into routine practice.

PMID- 10203172
TI  - Field evaluation of a one-step dipstick assay for the diagnosis of human
      leptospirosis in the Seychelles.
AB  - OBJECTIVE AND METHOD: To compare the response of a dipstick assay (DSA) detecting
      Leptospira-specific immunoglobulin M (IgM) antibodies with that of an enzyme
      linked immunosorbent assay (ELISA), an indirect haemagglutination assay (IHA),
      the microagglutination test (MAT) and a polymerase chain reaction assay (PCR) in
      patients with leptospirosis confirmed by MAT alone or by MAT and/or PCR
      (MAT/PCR). RESULT: In 75 patients with acute leptospirosis diagnosed by MAT
      (respectively, 90 patients diagnosed by MAT/PCR), the response in paired early
      and convalescent sera was positive in 78.9% (67.9%) by DSA, 76.0% (67.8%) by
      ELISA, 58.7% (55.6%) by IHA, 44.0% (53.3%) by PCR, and 100% (90.0%) by MAT. In
      early serum only, the response in patients diagnosed by MAT (respectively by
      MAT/PCR) was positive in 36.0% (38.9%) by DSA, 36.0% (37.8%) by ELISA, 14.7%
      (18.9%) by IHA, 39.2% (48.3%) by PCR, and 53.3% (58.9%) by MAT titre > or =1:100.
      DSA detected the main serogroups implicated in human leptospirosis in Seychelles
      and demonstrated sensitivity comparable to ELISA. In 124 single sera from control
      subjects without overt disease, the response was positive in 4.8% by DSA, 3.2% by
      ELISA, 3.2% by IHA, 13.8% by PCR, 37.9% by MAT titre > or =1:100, and 2.4% by MAT
      titre > or =1:800, giving evidence of the frequency of both past and current
      subclinical infection in Seychelles and that DSA was less sensitive than MAT to
      detect moderate levels of leptospiral antibodies. CONCLUSION: DSA is a simple and
      reproducible assay well adapted to field conditions and could usefully contribute
      to the evaluation of leptospirosis in areas devoid of serological laboratory
      facilities.

PMID- 10203173
TI  - Independent evaluation of the Nigrosin-Eosin modification of the Kato-Katz
      technique.
AB  - A new modified quantitative Kato-Katz thick-smear technique for the detection of
      helminth eggs in faeces preserves hookworm eggs unaltered for a long time, while
      with the classic Kato-Katz technique, they disappear after approximately 2 h in
      tropical climates and thus slides must be read within hours after sample
      collection. For an independent comparison of these two laboratory techniques,
      faecal smears from 263 school children were examined in two surveys and
      prevalence, intensity of infection and costs of surveys calculated. There was no
      statistical difference between the methods in detecting prevalence and
      stratification of the sample in different classes of intensity. While there was
      no statistical difference for the arithmetic mean of the epg for T. trichiura and
      only a small difference for A. lumbricoides (P=0.04), we observed a highly
      significant difference for hookworm mean intensities of infections (P<0.001).
      From the public health viewpoint both methods provided similar results, but due
      to its simplicity and widespread use the classical Kato-Katz technique remains
      first choice for community investigation of soil-transmitted nematodes. However,
      the Nigrosin-Eosin approach has several advantages and can be a valuable
      alternative in certain circumstances.

PMID- 10203174
TI  - Wild poliovirus circulation among healthy children immunized with oral polio
      vaccine in Antananarivo, Madagascar.
AB  - From July 1995 to December 1996, 3185 stool specimens from healthy children aged
      6-59 months attending 6 dispensaries in the Antananarivo area were examined for
      poliovirus. The children had been routinely immunized according to the Expanded
      Programme on Immunization (EPI) schedule and received the last dose of oral polio
      vaccine (OPV) more than 1 month before stool collection. 99.4% of the children
      were immunized with at least 3 doses of OPV. HEp-2 cell culture revealed virus
      infections in 192 stools (6.0%), including 9 poliovirus (0.3%) and 183 nonpolio
      enterovirus isolates (5.7%). Infections occurred throughout the year, but
      incidence was higher during the hot and rainy season (P=0.01). Using a
      neutralization test with monoclonal antibodies and PCR-RFLP in two genomic
      regions coding for the VP1 capsid and RNA polymerase, 4 wild polioviruses (3 type
      1 and 1 type 3) and 5 vaccine-related polioviruses (2 Sabin 1-like variants, 1
      Sabin 2-like and 2 Sabin 3-like) strains were identified. The wild polioviruses
      were isolated at the beginning and the end of the dry season. Similar RFLP
      patterns were observed for the 3 wild type 1 polioviruses. Comparison of partial
      genomic sequences in the VP1/2 A region of 1 of the wild type 1 isolates with 2
      wild type strains isolated in Antananarivo in 1992 and 1993 showed a divergence
      of at least 10% between the strains, suggesting at least two different pathways
      of transmission during this period. Our findings demonstrate that immunization
      with 3 doses of OPV did not prevent intestinal carriage of wild poliovirus
      strains, and that there is a risk of wild poliovirus transmission to susceptible
      children in the area. Multiple strategies are required to improve immunization
      coverage in Madagascar.

PMID- 10203175
TI  - Deriving meteorological variables across Africa for the study and control of
      vector-borne disease: a comparison of remote sensing and spatial interpolation of
      climate.
AB  - This paper presents the results of an investigation into the utility of remote
      sensing (RS) using meteorological satellites sensors and spatial interpolation
      (SI) of data from meteorological stations, for the prediction of spatial
      variation in monthly climate across continental Africa in 1990. Information from
      the Advanced Very High Resolution Radiometer (AVHRR) of the National Oceanic and
      Atmospheric Administration's (NOAA) polar-orbiting meteorological satellites was
      used to estimate land surface temperature (LST) and atmospheric moisture. Cold
      cloud duration (CCD) data derived from the High Resolution Radiometer (HRR) on
      board the European Meteorological Satellite programme's (EUMETSAT) Meteosat
      satellite series were also used as a RS proxy measurement of rainfall.
      Temperature, atmospheric moisture and rainfall surfaces were independently
      derived from SI of measurements from the World Meteorological Organization (WMO)
      member stations of Africa. These meteorological station data were then used to
      test the accuracy of each methodology, so that the appropriateness of the two
      techniques for epidemiological research could be compared. SI was a more accurate
      predictor of temperature, whereas RS provided a better surrogate for rainfall;
      both were equally accurate at predicting atmospheric moisture. The implications
      of these results for mapping short and long-term climate change and hence their
      potential for the study and control of disease vectors are considered. Taking
      into account logistic and analytical problems, there were no clear conclusions
      regarding the optimality of either technique, but there was considerable
      potential for synergy.

PMID- 10203177
TI  - Incidence of substandard drugs in developing countries.

PMID- 10203176
TI  - Acute intravascular haemolysis (blackwater fever) after antimalarial treatment.

PMID- 10203178
TI  - The effects of ionizing radiation on DNA synthesis in eukaryotic cells.
AB  - PURPOSE: To review observations of the effects of ionizing radiation on DNA
      synthesis in eukaryotes. CONTENT: Available information broadly falls into two
      categories: descriptions of the phenomenon, including dose response data and
      analysis; and, more recently, investigations utilizing genetic approaches. The
      down-regulation of DNA replication in the presence of radiation-induced DNA
      damage appears to be an active cellular response, termed the S-phase damage
      sensing (SDS) checkpoint control (Larner et al. 1997). Observations on a variety
      of eukaryotes, including man, suggest that the regulatory controls involved are
      highly conserved and may additionally function in G1 and G2 checkpoint controls.
      Budding yeast, fission yeast and human homologues are identified. CONCLUSIONS:
      The SDS checkpoint control appears to be comprised of a complex of checkpoint
      proteins that respond to the stalled replication complex. The replication complex
      is thought to signal down-regulation of the mitotic kinase, ensuring that the
      cell does not enter mitosis while S phase is delayed. Concomitantly, the
      checkpoint complex is believed to transmit a signal via two key checkpoint
      proteins (Rad3 and Cds1 in the fission yeast), in order to arrest further DNA
      synthesis initiation.

PMID- 10203179
TI  - Functional inactivation of p53 by HPV-E6 transformation is associated with a
      reduced expression of radiation-induced potentially lethal damage.
AB  - PURPOSE: To examine the effect of functional loss of p53 on radiation sensitivity
      and potentially lethal damage repair (PLDR). MATERIALS AND METHODS: Radiation
      sensitivity and PLDR were examined in an isogenic pair of human tumour cell lines
      created by HPV-E6 transformation. RESULTS: Inactivation of p53 by E6
      transformation resulted in a cell line that was more resistant to killing by
      radiation but showed little enhancement in survival (PLDR) when plateau-phase
      cells were held non-cycling after radiation exposure. Holding p53-normal cells in
      plateau-phase after radiation exposure not only led to enhanced survival, but
      also to a reduction in the proportion of cells that blocked in G1 subsequent to
      release. CONCLUSIONS: These results suggest that p53 expression influences that
      component of radiation sensitivity associated with PLDR.

PMID- 10203180
TI  - Correlation between cell reproductive death and chromosome aberrations assessed
      by FISH for low and high doses of radiation and sensitization by iodo
      deoxyuridine in human SW-1573 cells.
AB  - PURPOSE: To study the relationship between cell reproductive death and exchange
      frequency in SW-1573 human lung tumour cells with and without incorporated iodo
      deoxyuridine (IdUrd) following irradiation of plateau-phase cultures with y-rays.
      METHOD: Linear-quadratic (LQ) analysis was performed for the data on clonogenic
      survival and on the frequency of chromosomal exchanges studied with fluorescence
      in situ hybridization in chromosomes X and 2. RESULTS: Differences in the LQ
      parameters alpha and beta of both non-sensitized and sensitized chromosomes were
      found. In both chromosomes an increase in the number of chromosomal exchanges in
      IdUrd-radiosensitized cells compared with non-sensitized cells was observed. The
      alpha-enhancement factors of 1.7 and 1.9 for the X-chromosome and for chromosome
      2, respectively, are similar. For the X-chromosome, the beta coefficient
      increased by a factor of 3.9 and for chromosome 2 by a factor of 1.4. After
      correction to a full genome equivalence, no significant difference in alpha was
      found between chromosomes X and 2 for both control and sensitized cells. In
      contrast, an almost 2.8 times higher beta was found for the sensitized X
      chromosome compared to this value for chromosome 2. CONCLUSIONS: It can be
      concluded that the linear-quadratic analysis of dose-response relationships
      offers insights into the correlation between cell survival and induction of
      exchanges in non-sensitized and radiosensitized cells.

PMID- 10203181
TI  - Ultraviolet radiation down-regulates expression of the cell-cycle inhibitor
      p21WAF1/CIP1 in human cancer cells independently of p53.
AB  - PURPOSE: To investigate the regulation of G1 cyclin-dependent kinase inhibitor
      p21WAF1/CIP1 by ultraviolet (UV) radiation in human carcinoma cells. MATERIALS
      AND METHODS: Human cancer cell lines were irradiated with UV-C (254 nm)
      radiation, and their responses were characterized by Western blotting, Northern
      blotting, semi-quantitative RT-PCR analysis, trypan blue staining and flow
      cytometric cell cycle analysis. RESULTS: At 24 h after UV irradiation, p21
      expression was down-regulated in various cancer cell types (breast, prostrate,
      cervix, colon, glioma, squamous cancers), independently of their p53 genetic and
      functional status. UV-mediated down-regulation of p21 was dose- and time
      dependent, was observed at the protein and mRNA levels, and did not correlate
      with cytotoxicity. Reduction of p21 protein levels required about 4 and 1 h,
      respectively, in MCF-7 and MDA-MB-231 breast cancer cells; some of the UV-induced
      decreases in p21 levels in these cell lines was due to enhanced proteasomal
      degradation. Despite decreased p21 levels, UV-irradiated breast cancer cells with
      wild-type p53 (MCF-7) retained the capacity for G1 cell-cycle arrest, whereas UV
      treated cells with mutant p53 (MDA-MB-231) accumulated in S phase, suggesting a
      p53-dependent G1 checkpoint in MCF-7. UV treatment caused other alterations in
      cell-cycle regulatory, DNA repair and tumour suppressor genes, as described in
      this report. CONCLUSIONS: In contrast to X-rays, UV causes down-regulation of the
      cell-cycle inhibitor p21 in tumour cells. It is postulated that this may be an
      adaptation to promote the growth and survival of transformed cells.

PMID- 10203182
TI  - Harmful effects of UVA on the structure and barrier function of engineered human
      cutaneous tissues.
AB  - PURPOSE: To investigate the effects of a single UVA exposure on engineered human
      cutaneous tissues. MATERIALS AND METHODS: Skin equivalents (SE) were obtained by
      culturing keratinocytes on fibroblast-populated collagen gels; epidermal
      equivalents (EE) were obtained by seeding keratinocytes on non-populated collagen
      gels. After maturation and differentiation of the epidermis, SE and EE were
      exposed to 50 or 100 J/cm2 UVA. Structural damage and total epidermal lipids were
      analysed and diffusion of radioactive oestradiol was monitored 24 and 72h post
      irradiation. RESULTS: Twenty-four hours after UVA irradiation, a disorganization
      of the living epidermis is observed. UVA also significantly reduced the skin
      barrier function and led to an increase in phospholipid and in a decrease of
      ceramide levels. However, both the structure and the barrier function of SE were
      recovered 72 h post-irradiation, thereby suggesting that an intrinsic repair
      process might exist within the irradiated SE. CONCLUSION: This study provides a
      strong evidence that UVA radiation alters both the epidermal and dermal
      structures, the synthesis of epidermal lipids, and the permeability of the human
      skin.

PMID- 10203183
TI  - Radiation effect on rat Sertoli cell function in vitro and in vivo.
AB  - PURPOSE: To investigate the response of Sertoli cell function to 60Co gamma-rays.
      MATERIALS AND METHODS: Rat Sertoli cells were exposed in vitro and in vivo to
      60Co gamma-rays in the dose range 3 Gy to 48 Gy and at 3 Gy and 6 Gy
      respectively. Cell viability and transferrin and IL-6 production were measured at
      different times following irradiation. RESULTS: This study confirms the
      resistance of in vitro irradiated rat Sertoli cells in the dose range 3 Gy to 48
      Gy in terms of cell number. Radiation had no effect on the IL-1 activity of
      Sertoli cells. However, the experiments show that despite the absence of a
      macroscopic effect, Sertoli cells respond to ionizing radiation by increasing
      transferrin secretion, transferrin response to (Bu)2cAMP stimulation and IL-6
      activity. CONCLUSIONS: Transferrin is involved in the transport of iron into germ
      cells and in cell differentiation. IL-6 is a potent inhibitor of meiotic DNA
      synthesis. Radio-induced transferrin and IL-6 could play a role in the protection
      of germ cells and could explain, in part, the resistance of Sertoli cells to
      radiation.

PMID- 10203184
TI  - Influence of gamma-rays on the mouse liver cytochrome P450 system and its
      modulation by phenothiazine drugs.
AB  - PURPOSE: Phenothiazine drugs have been found to sensitize hypoxic cancer cells
      while offering protection to normal cells. Since phenothiazines are known to
      induce the cytochrome P450 system, its radiomodulation by phenothiazines has been
      examined. MATERIALS AND METHODS: Mice were administered phenothiazines
      intraperitoneally and irradiated with different doses of gamma-rays at 1.38
      Gy/min. The activities of NADPH-cytochrome P450 reductase and NADH-cytochrome b5
      reductase, the content of cytochrome P450 and b5, the extent of lipid
      peroxidation as well as the activities of LDH, XO, SOD, GST and DTD were
      determined in the liver. RESULTS: The levels of different components of the
      cytochrome P450 system and antioxidant enzymes were enhanced up to 5 Gy and
      decreased thereafter. However, a progressive increase was noticed in peroxidative
      damage and the activities of LDH and XO. Administration of phenothiazines
      enhanced the radiation effect on components of the cytochrome P450 system (except
      NADH-cytochrome b5 reductase) and the activities of SOD, GST and DTD.
      Concomitantly, phenothiazines inhibited lipid peroxidation, LDH and XO.
      CONCLUSIONS: Activation of the cytochrome P450 system by phenothiazines leading
      to the enhancement of antioxidant potential of animals and free-radical
      scavenging are attributes of the radioprotective action of phenothiazines.

PMID- 10203185
TI  - Adaptive response and dose-response plateaus for initiation in a state-vector
      model of carcinogenesis.
AB  - PURPOSE: To investigate whether it is possible to explain dose-response plateaus
      for in-vitro X-ray irradiation of different cell lines with radioprotective
      mechanisms such as radiologically induced expression of scavengers and repair
      enzymes. MATERIALS AND METHODS: A biomathematical model was developed based on a
      previous state-vector model. New features of the model are a mathematical
      description of enhanced repair and radical scavenging as a result of irradiation.
      RESULTS: The model produces a plateau in the dose-response for in-vitro
      tranformations between 0.5 and 1 Gy and for chromosome aberrations and it
      predicts an inverse-fractionation effect within a selected range of doses.
      CONCLUSIONS: Adaptive response mechanisms within a state-vector model provide a
      coherent explanation of the dose-response characteristics for in-vitro
      transformations and chromosomal aberrations. These results suggest the need for
      new experimental studies described in the paper.

PMID- 10203186
TI  - Role of endothelial factors in the specific response of mouse tumour-feeding
      arterioles to stimulation of 5-HT1 receptors.
AB  - PURPOSE: To investigate the possible role of endothelial mediators on the
      increased vasoconstriction to 5-HT1 receptor stimulation by the host-modified
      arterioles feeding a Meth-A tumour implanted in the flank of female Balb/c mice.
      MATERIALS AND METHODS: Using intravital microscopy, the response to the topical
      administration of the general 5-HT1 agonist 5-carboxamidotryptamine maleate (5
      CT; 10(-6) M to 10(-4) M) by the tumour-feeding arterioles with the responses of
      tumour-independent arterioles and those of control arterioles from mice without
      tumour after antagonization or inhibition of the synthesis of endothelial
      mediators was compared. RESULTS: The dramatically higher vasoconstriction to 5-CT
      observed in tumour-feeding arterioles than in tumour-independent or control
      arterioles still persisted when either nitric oxide synthase, cyclooxygenase,
      lipoxygenase, or phospholipase A2 were inhibited or when thromboxane A2 or
      endothelin were antagonized. CONCLUSIONS: It was concluded that the higher
      reactivity to 5-HT1 stimulation by tumour-feeding arterioles is not due to
      changes in endothelial mediator release but probably due to changes affecting
      arteriolar smooth muscle.

PMID- 10203187
TI  - The effects of the initial lung deposit on uranium biokinetics after
      administration as UF4 and UO4.
AB  - This study was designed to assess the effect of the initial lung deposit (ILD) on
      uranium biokinetics in rats after intracheal instillation of biologically soluble
      uranium compounds. Rats received various doses of either UO4 or UF4 dust. The
      uranium content was determined in the kidneys, lungs, remaining carcass, urine
      and faeces at intervals of up to 30 days. The percentages of uranium absorbed
      into blood, transferred to tissues, and excreted in urine were independent of the
      uranium lung deposit for the two compounds. The K/K + U ratio 24 h after
      installation (K is the per cent of uranium retained in the kidneys and U the per
      cent excreted in urine) which can be used to evaluate kidney function, was
      essentially constant in the range from 0.02 to 12.5 microg U g(-1) kidneys.

PMID- 10203188
TI  - Poloxamine 1107 sealing of radiopermeabilized erythrocyte membranes.
AB  - PURPOSE: Lipid peroxidation-mediated permeabilization of cell membranes following
      intense ionizing irradiation is well documented. This form of membrane
      radiopermeabilization leads to rapid exhaustion of cellular high-energy
      compounds, resulting in the acute onset of cellular necrosis. Strategies to
      reverse the process of necrosis and preserve cell viability require membrane
      sealing. This report documents the relative efficacy of Poloxamine 1107, a non
      ionic surfactant, compared with other polymers, in sealing radiopermeabilized
      cell membranes. MATERIALS AND METHODS: Isolated erythrocytes were exposed to 600
      Gy 60Co irradiation at a dose rate of 1.3 Gy/s. Different polymer compounds were
      added 10 min later to the irradiated cell suspensions. At 2 h later the
      haemoglobin content in the supernatants was determined spectrophotometrically.
      RESULTS: Compared with the non-treated irradiated control, Poloxamine 1107
      significantly reduced the leakage of haemoglobin from irradiated erythrocytes.
      Poloxamer 188 and dextran at equal concentrations had no significant reverse
      effect on the irradiation-mediated increased membrane permeability. The amount of
      haemoglobin released from irradiated erythrocytes was inversely related to the
      Poloxamine 1107 concentration. CONCLUSIONS: This study demonstrates the
      capability of Poloxamine 1107 to seal radiopermeabilized cell membranes. Thus,
      surfactants such as Poloxamine 1107 might be useful as a therapeutic agent in the
      treatment of high-dose radiation injuries since cellular necrosis due to
      metabolic exhaustion following radiopermeabilization of their membranes might be
      prevented.

PMID- 10203189
TI  - Diatom motility: the search for independent replication of biological effects of
      extremely low-frequency electromagnetic fields.
AB  - PURPOSE: To investigate the hypothesis that exposure to a certain combination of
      static and time-varying electromagnetic fields (EMF) results in an increase in
      motility of the marine diatom Amphora coffeaeformis. MATERIALS AND METHODS:
      Diatom motility on agar was positively correlated with calcium ion (Ca2+)
      concentration. In previous experiments extremely low frequency EMF (16 Hz) had
      the greatest effect on diatoms at suboptimal for movement Ca2+ concentrations. To
      ensure that the required suboptimal Ca2+ concentration and resultant cell
      motility were found, a number of low concentrations of Ca2+ were experimentally
      tested. The EMF exposure conditions were those at the calculated calcium
      resonances (B(V)=0 microT; B(H)=20.9 microT; B(AC)=41.8 microT peak-peak 16 Hz)
      previously found to cause enhanced motility. Diatom movement on agar plates under
      EMF and control exposures was recorded. RESULTS: There was no significant
      difference in cell motility between control and EMF-exposed diatoms at each Ca2+
      concentration tested. CONCLUSIONS: The study indicates that low-frequency EMF set
      at resonance conditions did not cause an increase in motility of the diatoms.

PMID- 10203190
TI  - An evolutionary analytical model of a complementary circular code.
AB  - The subset X0=[AAC,AAT,ACC,ATC,ATT,CAG,CTC,CTG,
      GAA,GAC,GAG,GAT,GCC,GGC,GGT,GTA,GTC,GTT,TAC,TTC] of 20 trinucleotides has a
      preferential occurrence in the frame 0 (reading frame established by the ATG
      start trinucleotide) of protein (coding) genes of both prokaryotes and
      eukaryotes. This subset X0 is a complementary maximal circular code with two
      permutated maximal circular codes X1 and X2 in the frames 1 and 2 respectively
      (frame 0 shifted by one and two nucleotides respectively in the 5'-3' direction).
      X0 is called a C3 code (Arques and Michel, 1997, J. Biosyst 44, 107-134). A
      quantitative study of these three subsets X0, X1 and X2 in the three frames 0, 1
      and 2 of eukaryotic protein genes shows that their occurrence frequencies are
      constant functions of the trinucleotide positions in the sequences. The
      frequencies of X0, X1 and X2 in the frame 0 of eukaryotic protein genes are
      48.5%, 29% and 22.5% respectively. These properties are not observed in the 5'
      and 3' regions of eukaryotes where X0, X1 and X2 occur with variable frequencies
      around the random value (1/3). Several frequency asymmetries unexpectedly
      observed, e.g. the frequency difference between X1 and X2 in the frame 0, are
      related to a new property of the C3 code X0 involving substitutions. An
      evolutionary analytical model at three parameters (p, q, t) based on an
      independent mixing of the 20 codons (trinucleotides in the frame 0) of X0 with
      equiprobability (1/20) followed by t approximately 4 substitutions per codon
      according to the proportions p approximately 0.1, q approximately 0.1 and r = 1 -
      p - q approximately 0.8 in the three codon sites respectively, retrieves the
      frequencies of X0, X1 and X2 observed in the three frames of protein genes and
      explains these asymmetries. The complex behaviour of these analytical curves is
      totally unexpected and a priori difficult to imagine. Finally, the evolutionary
      analytical method developed could be applied to the phylogenetic tree
      reconstruction and the DNA sequence alignment.

PMID- 10203191
TI  - Memory retrieval as a p-adic dynamical system.
AB  - We propose a mathematical model of the memory retrieval process based on
      dynamical systems over a metric space of p-adic numbers representing a
      configuration 'space of ideas' in which two ideas are close if they have a
      sufficiently long common root. Our aim is to suggest a new way of conceptualizing
      human memory retrieval that might be useful for simulation purposes or for the
      construction of artificial intelligence devices, as well as for a deeper
      understanding of the process itself. The dynamical system is assumed to be
      located in a blackbox processing unit (the 'subconscious') and controlled by an
      interface control unit (the 'conscious') that fixes parameters in the dynamical
      system and starts its iteration by sending an initial generating idea to it. We
      show that even simple p-adic dynamical systems admit behavioral scenarios that
      could explain some of the essential features of the human memory retrieval
      process.

PMID- 10203192
TI  - DNA dynamics and endogeneous fields.
AB  - In this paper we investigate the influence of endogeneous AC fields, generated by
      a living cell itself, on DNA dynamics. Both quantum nonlinear vibron-phonon
      interaction model and a model of a highly localized excitation are used. The
      transition of a broad solitonic excitation into a highly localized one affected
      by AC fields is calculated using Kubo's formalism for linear response of the
      system.

PMID- 10203193
TI  - Characterizing critical rules at the 'edge of chaos'.
AB  - This paper aims to provide a deeper understanding of the 'edge of chaos'
      phenomenon. This is an important concept in some strands of work on complex
      systems, but exactly what it means remains unclear. Broadly, it may be seen as a
      region between rigid order and chaos. In cellular automata which show the edge of
      chaos phenomenon, this is indicated by the occurrence of smooth transitions in
      certain variables, such as the average Shannonian entropy, where generally one
      finds sudden jumps. The abrupt jump is between an ordered realm and a chaotic
      one, so the smoothness of a transition holds out the promise of the existence of
      a realm between order and chaos. Since living systems may also be described as
      lying between order and chaos, then the edge of chaos may be the key to
      understanding the form of organization which characterizes life. The smooth
      transitions in 2-D cellular automata were therefore investigated in detail to see
      whether it is possible to characterize the cellular automata rules which give
      rise to them. It was found that the transitions were smoother the less that there
      was a marked jump in the number of rule table entries applied. But, the bare fact
      of this correspondence does not reveal the cause of the smoothness. Further work
      was therefore carried out to try to understand more about what led to the smooth
      behaviour. However in two further studies in which 'smooth rules' were slightly
      altered and in which the dominant parts of a 'smooth rule' were imposed on other
      rules, it was found that the rules which led to a smooth transition were very
      sensitive to small changes. A change of less than 0.05% of the rule table entries
      of a 'smooth rule' was more than likely to lead to an abrupt rather than smooth
      transition. This suggests that it may prove difficult to understand what it is
      about the rules which leads to the edge of chaos.

PMID- 10203194
TI  - Evaluation of characteristic parameters for the neurotransmitter release
      mechanisms at the neuromuscular junction.
AB  - The process of neurotransmitter release at the neuromuscular junction needs to be
      represented appropriately in modeling of the synaptic chemical transmission as a
      reaction-diffusion system. The release mechanisms of the expanding pore and the
      acceleration are analyzed by the computer simulation with respect to the effects
      of the characteristic parameters in the mechanisms on spontaneous generation of
      the miniature endplate current (MEPC), leading to the following evaluation. In
      the expanding pore mechanism the expanding rate of the pore more than 10 nm ms(
      1) and the diffusion coefficient of acetylcholine in the synaptic cleft (D(c)) of
      about 1.0 x 10(-6) cm2 s(-1) yield the maximum amplitude, the rise time and the
      decay time constant of the MEPC in agreement with the empirical data. In the
      active release mechanism the 10-fold acceleration of the natural diffusion and a
      similar value of D(c) are required to suit for the empirical MEPC.

PMID- 10203195
TI  - Quantifying elasticity analysis: how external effectors cause changes to
      metabolic systems.
AB  - The sites of action of external effectors, such as inhibitors or hormones, on
      metabolic systems can be described qualitatively by elasticity analysis, or
      quantitatively by regulation analysis. The use of the latter approach has been
      limited, due to its practical complexity. In this study, we report mathematical
      relationships that relate the finite changes in system variables (fluxes and
      metabolite concentrations) to changes in activity of metabolic processes brought
      about by a single step addition of an effector. The activation or inhibition of a
      process by an effector is measured from changes in flux and intermediate levels.
      The changes in activity of each process can be used to describe, semi
      quantitatively, which activations or inhibitions of the system processes are
      important in bringing about the observed levels of system variables.

PMID- 10203196
TI  - Journals of geriatric medicine and gerontology.

PMID- 10203197
TI  - Popliteal aneurysm: the need for vigilance.

PMID- 10203198
TI  - Intermittent compression for the treatment of the oedematous hand in hemiplegic
      stroke: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate the efficacy of intermittent pneumatic compression in
      treating oedema in the hemiplegic hand of stroke patients. DESIGN: Single-blind
      randomized control trial. SETTING: acute and rehabilitation elderly care wards in
      a teaching district. SUBJECTS: 37 Subjects with a first ever hemisphere stroke
      were randomized to treatment with standard physiotherapy either alone or combined
      with intermittent pneumatic compression. MAIN OUTCOME MEASURES: The effect of
      treatment on oedema was assessed using measures of the hand volume of the
      hemiplegic hand. The impact on function was assessed using the motricity index.
      RESULTS: The treated group showed no change in the mean stroke hand volume. In
      the control group the mean stroke hand volume decreased by 3.2 ml. There was no
      statistically significant difference between the groups. The median scores for
      the motricity index increased for both groups but there was no significant
      difference between the groups and any improvement in motor function was
      independent of any treatment effects. CONCLUSION: Intermittent pneumatic
      compression at the prescribed pressure and duration of this study is not an
      effective treatment for the oedematous stroke hand.

PMID- 10203199
TI  - Symptoms reported by elderly patients with isolated systolic hypertension:
      baseline data from the SYST-EUR trial. Systolic Hypertension in Europe.
AB  - OBJECTIVES: To determine the symptomatic well-being of elderly persons with
      isolated systolic hypertension. DESIGN AND SETTING: Well-being determined during
      the placebo run-in period prior to entry to the Systolic Hypertension in Europe
      (SYST-EUR) trial. SUBJECTS: 641 People, 60 years or older with an average sitting
      blood pressure of 173/86 mm Hg. OUTCOME MEASURES: 33 Symptomatic complaints
      determined by a standard interview. RESULTS: The 437 women complained of 25% of
      the symptoms and the 204 men 21% (P<0.001). A markedly higher prevalence was
      observed in women compared with men for: pain in the joints of the hands (35% of
      women complained of this against 22% of men); 'racing heart' (33% against 17%);
      dry eyes (16% against 6%); blurring of vision (35% against 23%); cramps in the
      legs (43% against 31%); and a sore throat (15% against 7%). Nocturia was the most
      frequent complaint (68% in both sexes). Eight symptoms increased with age and one
      (rash) tended to decline. With increasing systolic pressure women also reported
      more headaches, unsteadiness, blurring of vision, irregular heart beat and
      'racing heart' but, of these, only headaches increased with diastolic pressure.
      These observations were made after adjusting for age, blood sugar and body mass
      index (BMI) and were not observed in men. Higher blood sugars were associated
      with mouth ulcers, 'racing heart', blurring of vision and cramps in the legs. A
      higher BMI was associated with six symptoms, and a lower age of leaving education
      with eight. In men, alcohol consumption was related to 'racing heart', and
      smoking to wheezing and having a dry cough. CONCLUSIONS: A high level of
      complaint was associated with female gender, increasing age, blood sugar and BMI
      and a low age of leaving education.

PMID- 10203200
TI  - Blood pressure rhythm and prevalence of vascular events in hypertensive subjects.
AB  - OBJECTIVES: To evaluate the influence of age on the day-night blood pressure
      rhythm and on the prevalence of vascular events in those whose systolic blood
      pressure (SBP) fell by <10% overnight (non-dippers). DESIGN: Cross-sectional
      observational cohort study. SETTING: Outpatient hypertension clinic.
      PARTICIPANTS: 419 Hypertensive patients (214 male, 205 female). METHODS: All
      subjects were submitted to ambulatory blood pressure monitoring (Spacelabs
      90207). The nocturnal fall of SBP was calculated from (day SBP--night SBP)/day
      SBP, where 'day' values were recorded between 0600 h and 2200 h and 'night'
      values between 2200 h and 0600 h. Dippers and non-dippers were divided in two
      subgroups according to age (under or over 65 years). Information on gender,
      smoking, diabetes mellitus and body mass index was collected and cerebrovascular
      and cardiovascular events, evaluated by history and medical records, were
      registered. RESULTS: The day-night difference in blood pressure significantly
      decreased with age and the prevalence of non-dippers was greater in elderly than
      in younger subjects (65.1% vs. 29.8%). No difference was found between groups for
      cerebrovascular events, irrespective of age. A relationship between non-dipping
      pattern and cardiovascular events was found only in younger hypertensive non
      dippers (odds ratio, 2.0; 95% confidence interval, 1.20-3.21); in elderly people
      the prevalence of cardiovascular events was similar in dippers and non-dippers.
      CONCLUSIONS: Cardiovascular risk is not increased in elderly non-dipper
      hypertensive subjects. This contrasts with results in younger populations.

PMID- 10203201
TI  - Total and functional hepatic blood flow decrease in parallel with ageing.
AB  - OBJECTIVES: To study changes in hepatic blood flow with age. DESIGN: Functional
      hepatic flow (FHF) and total hepatic flow (THF) were determined by non-invasive
      methods in 40 normal subjects in four age groups (<45, 45-60, 61-75 and >75
      years). All subjects had normal routine liver function tests and no history of
      liver disease. RESULTS: THF was measured by pulsed echo-Doppler, as the sum of
      portal and hepatic artery blood flow; FHF was measured by the hepatic clearance
      of D-sorbitol. THF significantly decreased with age, particularly in subjects
      over 75 (from 1445+/-220 ml/min to 1020+/-148; P<0.001), and a similar reduction
      was observed in FHF (from 1514+/-250 ml/min to 1015+/-163; P<0.001). THF and FHF
      were strictly correlated in the whole population (r = 0.871; P<0.001) and both
      correlated with age (r = -0.510 and r = -0.596; P<0.005). CONCLUSION: With ageing
      there is a reduction of hepatic blood flow without any additional intrahepatic
      shunting.

PMID- 10203202
TI  - Use of the GDS-15 geriatric depression scale as a screening instrument for
      depressive symptomatology in patients with Parkinson's disease and their carers
      in the community.
AB  - OBJECTIVES: To assess the level of depressive symptomatology in a community based
      group of patients with Parkinson's disease (PD) and their carers and to
      investigate the patient characteristics that might predict carer distress.
      METHODS: The GDS-15 geriatric depression scale was used to measure self-rated
      depressive symptoms in a group of 132 subjects with clinically probable PD
      randomly selected from a community-based disease register. Disease severity was
      assessed by the Webster scale and cognitive function by the CAMCOG test. Carers
      of the patients, who in this study were all spouses, were also asked to complete
      the GDS-15. RESULTS: A total of 64% of our group of patients and 34% of carers
      scored within the 'depressed' range on the GDS-15. Patients with high levels of
      depressive symptoms tended to have more severe disease, disease of longer
      duration and more impaired cognitive function. The GDS score of the carer was
      best predicted by the GDS score of the patient being cared for. Less than 10% of
      patients and carers were being treated with antidepressant medication.
      CONCLUSIONS: This community-based study confirms the high level of depressive
      symptoms in PD suggested by hospital- and clinic-based studies. Depression in
      patients appears to be related to disease severity and cognitive impairment. An
      important determinant of carer distress and mood disorder, as reflected by the
      GDS score, appears to be the level of depression expressed by the patient being
      cared for. Despite high levels of depressive symptoms in both patients and
      carers, very few subjects were in receipt of antidepressant drug therapy.

PMID- 10203203
TI  - The detection of dementia and cognitive impairment in a community population of
      elderly people with Parkinson's disease by use of the CAMCOG neuropsychological
      test.
AB  - AIM: To assess cognitive function in elderly subjects with clinically probable
      Parkinson's disease (PD). METHODS: A community sample of 126 patients with
      probable PD completed the CAMCOG, which is the cognitive section of the Cambridge
      Examination for Mental Disorders, and the Mini-Mental State Examination (MMSE).
      The performance of the CAMCOG and the MMSE in detecting dementia in this subject
      group was compared with the results of applying the DSM-IV criteria for dementia
      to this population. RESULTS: A total of 44% of the group met DSM-IV criteria for
      dementia, which is higher than most previous prevalence figures for dementia in
      PD. The CAMCOG was more sensitive than the MMSE in detecting cognitive impairment
      and more specific than the MMSE in detecting dementia as defined by DSM-IV
      criteria. Poorer performance on the CAMCOG was related to gender, social class
      and age (P<0.05). Among subjects with PD, those with dementia, as defined by DSM
      IV criteria, were significantly older, had greater depressive symptomatology and
      had greater motor deficits. A greater proportion of the group with dementia were
      living in residential care (P<0.05). CONCLUSION: The CAMCOG appears to be a
      useful screening instrument for dementia and cognitive impairment in PD.
      Furthermore, it may prove helpful in detecting those with PD who may be at risk
      of developing dementia and in longitudinal studies of cognitive function in PD.

PMID- 10203204
TI  - Nursing home characteristics and the development of pressure sores and disruptive
      behaviour.
AB  - OBJECTIVE: To determine how nursing home characteristics affect pressure sores
      and disruptive behaviour. METHOD: Residents (n = 5518, aged > or =60 years) were
      selected from 70 nursing homes in the National Health Care chain. Homes were
      classified as high- or low-risk based on incidence tertiles of pressure sores or
      disruptive behaviour (1989-90). Point-prevalence and cumulative incidence of
      pressure sores and disruptive behaviour were examined along with other functional
      and service variables. RESULTS: The overall incidence of pressure sores was 11.4%
      and the relative risk was 4.3 times greater in high- than low-risk homes; for
      disruptive behaviour, the incidence was 27% and the relative risk was 7.1 times
      greater in the high-risk group. At baseline, fewer subjects in homes with a high
      risk of pressure sores were white or in restraints, but more had received
      physician visits monthly and had had problems with transfers and eating. High
      risk homes also had fewer beds and used less non-licensed nursing staff time. At
      follow-up (1987-90), 52% of homes in the low-risk group and 35% of those in the
      high-risk group had maintained their risk status; low-risk homes were more likely
      to have rehabilitation and maintenance activities. Having multiple clinical risk
      factors was associated with more pressure sores in high- (but not low-) risk
      homes, suggesting a care-burden threshold. By logistic regression, the best
      predictor of pressure sores was a home's prior (1987-88) incidence status.
      Interestingly, 67% of homes with a high risk of pressure sores were also high
      risk for disruptive behaviour, while only 27% of homes with a low risk of
      pressure sores were high-risk for disruptive behaviour. A threshold effect was
      also observed between multiple risk factors and behaviour. More homes with a high
      risk of disruptive behaviour (68%) remained at risk over 4 years, and the best
      predictor of outcome was a home's previous morbidity level. CONCLUSION: Nursing
      home characteristics may have a greater impact than clinical factors on pressure
      sores and disruptive behaviour in long-stay, institutionalized elders.

PMID- 10203205
TI  - A survey of attitudes and knowledge of geriatricians to driving in elderly
      patients.
AB  - OBJECTIVE: To assess the attitudes of consultant members of the British
      Geriatrics Society to elderly patients driving motor vehicles. DESIGN: An
      anonymous postal survey assessing knowledge and attitudes to driving in elderly
      people. A standardized questionnaire was used and five case histories were
      offered for interpretation. SETTING: The study was co-ordinated from a teaching
      hospital. SUBJECTS: The 709 consultant members of the British Geriatrics Society.
      Four hundred and eighteen responses were obtained, which represents a 59%
      response rate. RESULTS: 275 Respondents (68%) correctly realised that a person
      aged 70 had a duty to inform the Driving and Vehicle Licensing Authority (DVLA)
      about their eligibility to drive. The remainder did not. Most (315; 75%) believed
      that the overall responsibility for informing the DVLA was with the patient. If a
      patient was incapable of understanding advice on driving because of advanced
      dementia, 346 (83%) would breach patient confidentiality and inform the authority
      directly. Where a patient was fully capable of understanding medical advice but
      ignored it, 72% of geriatricians would have legitimately breached patient
      confidentiality and informed the DVLA. Most geriatricians (88%) saw their main
      role as one of providing advice on driving to patients and their families.
      Enforcing DVLA regulations was not seen as an appropriate function, unless the
      patient was a danger to themselves or other drivers. CONCLUSIONS: There is a wide
      variation in knowledge of driving regulations and attitudes to driving in elderly
      patients. Better education of geriatricians should improve awareness of when
      elderly drivers can safely continue to drive.

PMID- 10203206
TI  - The effects of age and alcohol intoxication on simulated driving performance,
      awareness and self-restraint.
AB  - AIMS: To investigate whether, compared with middle-aged men (aged 30-50), older
      men (age > or =60) (i) perform more poorly on a driving simulator and (ii) are
      more sensitive to the effects of ethanol in terms of blood alcohol concentration
      (BAC) and driving performance, but more aware of their driving difficulties, and
      therefore exercise better driving judgement. METHODS: 14 Healthy middle-aged men
      (mean age 36 years) were compared with 14 healthy older men (mean age 69 years)
      on an interactive driving simulator, while sober and while legally intoxicated
      (BAC >80 mg/dl). RESULTS: Older age was associated with poorer driving
      performance on the simulator. While sober, older men exhibited more improper
      braking, slower driving, greater speed variability, fewer appropriate full stops
      and more crashes, and spent more time executing left turns (across oncoming
      traffic); all values < or =0.02. BACs > or =80 mg/dl were associated with
      impaired driving, with more inappropriate braking, fewer appropriate full stops
      and more time executing left turns (all values > or =0.02) and trends towards
      more speed variability, more low speed collisions and more wrong turns (values
      <0.1). However, similar ethanol consumption did not produce higher peak BAC or
      more driving impairments in older drivers. While there were no differences
      between age groups in terms of awareness of intoxication or driving difficulties,
      older men were unwilling to drive while legally intoxicated because of fear of
      physical injury, whereas middle-aged men were more likely to avoid driving when
      intoxicated due to fear of legal ramifications. CONCLUSION: While both age and
      legal intoxication affected driving performance, older men were no more sensitive
      to ethanol in terms of peak BACs, driving performance or awareness/judgement than
      middle-aged men.

PMID- 10203207
TI  - A national survey of health-service use in Thai elders.
AB  - OBJECTIVES: To examine the pattern of health-service use and associated factors
      among elderly people in Thailand. DESIGN: A cross-sectional multi-stage random
      sampling household survey. SUBJECTS: 4480 People aged 60 and over. MAIN OUTCOME
      MEASURES: Responses to illness among elderly Thai subjects and health-service
      utilization. RESULTS: Of 1954 elderly Thai subjects who reported that they had
      had an illness without hospitalization during the last month, 93% had sought
      treatment and 7% did nothing. Just over a half (52.8%) used health services.
      Subjects who had self-limiting symptoms or diseases tended to not use health
      services, while subjects with chronic conditions did. Sixty-two percent paid for
      treatment themselves while 28% of them had their bills paid by their children.
      Independent determinants of health-service use included living in a rural area,
      being well-educated and better off, not drinking alcohol and the severity of
      illness identified. CONCLUSIONS: We found a low rate of state health-service use.
      Children had an important role in taking care of parents.

PMID- 10203208
TI  - Cardioversion for atrial fibrillation: the views of consultant physicians,
      geriatricians and cardiologists.
AB  - BACKGROUND AND AIMS: Atrial fibrillation (AF) increases the risk of stroke and
      also has adverse haemodynamic consequences. Cardioversion of AF to sinus rhythm
      may obviate the need for long-term anticoagulation and improve cardiovascular
      haemodynamics, but is probably underused. We therefore investigated the views of
      hospital consultants about cardioversion for AF. METHODS: 336 Postal
      questionnaires were sent to all 186 consultant physicians, 54 cardiologists and
      96 geriatricians in Scotland, followed by one reminder letter to non-responders.
      RESULTS: 71% Of questionnaires were returned. Cardiologists referred 18% of AF
      patients for cardioversion, while physicians referred 11% and geriatricians 5%.
      Cardiologists had better access to cardioversion facilities and were less likely
      to consider an enlarged left atrium and organic heart disease to be contra
      indications to cardioversion. Anticoagulation was given for less than 3 weeks
      before cardioversion by 9% of cardiologists, 39% of physicians and 65% of
      geriatricians (P<0.001), and for less than 3 weeks after cardioversion by 17% of
      cardiologists, 45% of physicians and 47% of geriatricians (P = 0.7). SUMMARY: The
      wide variation in practice both between and within the different specialties
      suggests that consensus guidelines based on the best available evidence should be
      developed.

PMID- 10203209
TI  - Improving the emergency medical treatment of older nursing-home residents.

PMID- 10203210
TI  - Pneumonia: projected age-related needs for hospital services in Finland.

PMID- 10203211
TI  - Are new medical students interested in the introduction of public long-term care
      insurance in Japan?

PMID- 10203212
TI  - Cardiopulmonary resuscitation training of Senior House Officers in oral and
      maxillofacial surgery in the UK.

PMID- 10203213
TI  - Comparison of recombinant and purified human bone morphogenetic protein.
AB  - Clinically, it would be more convenient to use recombinant than purified
      preparations of bone morphogenetic protein (BMP). Recently, recombinant human BMP
      (rhBMP) has attracted the attention of many investigators, but it has not been
      fully characterized. We examined the bone-inducing activity of rhBMP-2 and
      compared it with that of purified BMP derived from human bone matrix (phBMP).
      Two, 10, or 50 microg of rhBMP-2 or phBMP was mixed with 3 mg of atelopeptide
      type I collagen (carrier), and specimens were implanted in the calf muscles of
      Wistar rats (n=5 in each group). Four weeks later, new bone had formed in all the
      rhBMP-2- and phBMP-implanted muscles and was visible radiographically and
      histologically. The quantitative analysis indicated that the activity of rhBMP-2
      was less than one tenth that of phBMP. It is necessary to find out why rhBMP-2
      has fewer activities than phBMP.

PMID- 10203214
TI  - Biodegradable osteosynthesis in mandibular advancement: a pilot study.
AB  - In this pilot study four patients are presented who underwent bilateral sagittal
      split osteotomies of the mandibular ramus for mandibular advancement.
      Biodegradable osteosyntheses were used for internal fixation. All patients were
      from the same dentofacial category: mandibular retrognathia with a low to normal
      mandibular plane angle. In two patients cylindrical self-reinforced polyglycolide
      (PGA) rods were used for internal fixation of the osteotomy segments. Long-term
      evaluation showed a complete ossification at the sites of biodegradable rods. In
      two other patients, self-reinforced poly(L-lactide) (PLLA) screws with a diameter
      of 2 mm were used to stabilize osteotomy segments. The two different techniques
      of osteosynthesis and the problems encountered are discussed.

PMID- 10203215
TI  - Latex allergy in an orthognathic patient and implications for clinical
      management.
AB  - A 19-year-old girl with mild asthma had had 16 months of orthodontic treatment as
      part of the joint orthodontic/orthognathic approach to her 9.5 mm overjet. At the
      time of banding her second molars she developed latex protein allergy as a
      reaction to the operator's non-sterile powdered latex gloves. She also gave a
      history of allergy to other substances as well as of eczema. The patient was
      confirmed as allergic to latex protein by radioallergosorbent test (RAST) for
      IgE, requiring precautions be taken during further orthodontic procedures as well
      as during the subsequent orthognathic surgery for the underlying Class II
      skeletal pattern.

PMID- 10203216
TI  - Metallic fragments on the surface of miniplates and screws before insertion.
AB  - Particulate metal fragments have been identified histologically within the
      tissues adjacent to miniplates and screws after they have been removed. These
      were thought to have been caused by corrosion and degradation of the metal.
      However, the particles may have originated from rough edges or from protuberances
      left on the metal surface after cutting and machining during manufacture, and
      subsequently become detached. This study was undertaken to analyse the incidence
      and distribution of metal fragments on the surface of miniplates and screws
      before use. Fifteen miniplates and 60 screws were examined by stereomicroscopy
      and scanning electron microscopy. Rough metal edges or protuberances were
      identified on over half the samples, mostly in the countersink area of screw
      holes on the mini-plates. Fragments were detected within some of the cruciform
      screw heads and on some screw threads. We conclude that metal protuberances are
      present on the surface of mini-plate components when they are received from the
      manufacturer. There is a risk that the fragments might be detached and deposited
      into the tissues during insertion.

PMID- 10203217
TI  - Differences in cephalometric reference values between five centres: relevance to
      the Eurocleft Study.
AB  - Cephalometric data from five different geographical areas (Oslo, Manchester,
      London, Nijmegen, and Michigan) were compared. The angles SNA, SNB, and ANB were
      taken from published tables in the form of mean, standard deviation (SD) and
      number in the sample, divided up by age and sex. Angles SNA and SNB were
      significantly different among centres on univariate analysis. The Oslo data
      showed 23 instances in which they differed significantly from the other data,
      London 16, Manchester 11, Nijmegen 11, and Michigan 7. Multivariate analysis
      using Penrose distances were Oslo (2.04), Manchester (1.39), London (0.93),
      Nijmegen (0.80), and Michigan (0.66). The sums of the Mahalanobis distances were
      Nijmegen (3.60), Oslo (3.10), London (2.80), Manchester (2.25), and Michigan
      (1.49). As these results probably reflect racial and genetic differences, these
      must be taken into account when international comparisons are being made, as in
      the Eurocleft study.

PMID- 10203218
TI  - Anatomical basis and results of the facial artery musculomucosal flap for oral
      reconstruction.
AB  - The facial artery musculomucosal (FAMM) flap is a newly designed buccal mucosal
      flap that was first described in 1992. The long rotational arc of this flap is
      particularly suitable for anterior palatal defects that are otherwise difficult
      to treat with local flaps. However, after the first clinical reports, some
      controversies arose about the reliability of this flap, so we conducted an
      anatomical study of the vascular pattern with a latex preparation in 10 cadavers.
      We studied the variations of the course of the facial artery and focused on the
      relationship between the facial artery and vein within the pedicle. We concluded
      that the flap is more an arterialized flap than an axial-pattern flap, and have
      given anatomical landmarks to optimize the survival rate. Our preliminary
      clinical results (five good results, one complete failure) are acceptable.

PMID- 10203219
TI  - Lymph node metastases in hamster tongue cancer induced with 9,10-dimethyl-1,2
      benzanthracene: association between histological findings and the incidence of
      neck metastases, and the clinical implications for patients with tongue cancer.
AB  - An experimental study was carried out in hamster tongue cancer induced with 9,10
      dimethyl-1,2-benzanthracene (DMBA) to examine the association between the
      histological features and the incidence of lymph node metastases. Squamous cell
      carcinoma was induced in 64 of 71 hamsters exposed to DMBA 3 times weekly for a
      period of 10-24 weeks, and lymph node metastases were found in 8 necks. Various
      histological variables in the primary lesion were examined, and the mode of
      invasion, degree of keratinization, and stage of invasion were found to be
      closely related to the development of neck metastases. We then did a prospective
      study in 37 human patients with T1-2 tongue cancer, which also showed a close
      association between the incidence of neck metastases and the histological
      variables of mode of invasion and degree of keratinization. These experimental
      and clinical studies suggest that the mode of invasion and degree of
      keratinization may be risk factors for neck metastases that are independent of T
      stage, and that the indications for elective neck dissection should be re
      evaluated in that light.

PMID- 10203220
TI  - Localization of Fas antigen in oral squamous cell carcinoma.
AB  - Fas antigen is a cell-surface protein that transduces an apoptotic signal from
      the cell surface into the cytoplasm. The localization of Fas antigen in human
      oral squamous cell carcinoma (SCC) was examined by immunohistochemistry using a
      monospecific polyclonal antibody with a high titre. This antibody, designated as
      Fas D, was raised against a synthetic polypeptide segment corresponding to a
      specific extracellular domain of human Fas antigen (aa 104-114). Thirty-eight
      specimens of oral SCCs were stained with Fas D antibody and 26 (68%) reacted
      intensely. The specimens were graded as 'well', 'moderately', or 'poorly
      differentiated', according to the histopathological criteria. Out of 24 cases of
      the well differentiated tumours examined, 22 had reacted to Fas staining. The
      tumour cells formed nests that encompassed keratin pearls; staining was confined
      to cytoplasmic granules of peripheral cells. Among the moderately differentiated
      tumours, 4 out of 11 cases had reacted to Fas staining. No Fas-positive cells
      were observed in the poorly differentiated tumours, but only three specimens were
      examined. The expression of Fas antigen seems to be related to the degree of
      tumour differentiation.

PMID- 10203221
TI  - Clinical and magnetic resonance findings in the temporomandibular joints of
      patients before and after orthognathic surgery.
AB  - It is difficult to achieve the correct position of the condyle in the temporal
      fossa during orthognathic surgery in angle class II patients with disorders of
      the temporomandibular joint. This led us to examine the TMJ of 25 of our own
      patients before and shortly after orthognathic operations. We recorded the
      clinical and magnetic resonance imaging findings of the temporomandibular joint
      preoperatively and three months postoperatively. The patients had skeletal class
      II dysgnathia and had been treated with fixed orthodontic appliances for a mean
      of two years and three months before operation. Operation resulted in a mean
      reduction of maximal incisor distance of 12 mm. In five of the 25 patients, the
      pattern of mouth-opening changed. Nine patients had less pain than before
      surgery, and nine had fewer abnormal joint sounds. The magnetic resonance imaging
      showed displacement of the articular disc in 38 of the 50 joints preoperatively
      and in 28 postoperatively. Degenerative joint changes were not improved by
      operation. Improvement of the disc position was achieved by repositioning of the
      condylar-disc complex during orthognathic surgery in angle class II patients.
      Clinical and magnetic resonance imaging findings regarding the temporomandibular
      joint in class II patients correlated significantly both preoperatively and
      postoperatively.

PMID- 10203222
TI  - Does diplopia persist after blow-out fractures of the orbital floor in children?
AB  - Blow-out fractures of the orbital floor are comparatively rare in children,
      particularly those less than 8 years old. Published reports have suggested that
      the long-term outcome in children is worse than that in adults with similar
      injuries. In this study, we examine this question in the light of data from 45
      children from Birmingham and Glasgow who were divided into three age ranges: 0-9
      years (n = 9), 10-12 years (n = 11) and 13-15 years (n = 25). Fourteen were
      treated conservatively and 31 were treated surgically. The 0-9-year-old group
      were more likely to have small- or medium-sized defects in the anterior part of
      the orbital floor, which were of a linear 'trapdoor' type. The 13-15-year-olds
      tended to have larger 'open-door' defects. More than half the 0-9-year-olds had
      persistent diplopia compared with just under a third of the two other age groups.
      This diplopia took twice as long to resolve in the younger group compared with
      the other two groups. Our results confirm the view that younger patients have
      more persistent problems than adults after blow-out fractures of the orbital
      floor.

PMID- 10203223
TI  - Intermaxillary fixation is not usually necessary to reduce mandibular fractures.
AB  - We undertook a retrospective study of all isolated mandibular fractures which had
      required active management over a 1-year period at the Maxillofacial Unit at
      Newcastle General Hospital. Patients with single or multiple fractures of the
      mandible were included in the study, if there were other simultaneous fractures
      of the facial skeleton, those patients were excluded. All case notes and
      radiographs were reviewed by a single operator. A total of 202 cases of fractured
      mandible were identified of which 115 fulfilled the selection criteria of:
      isolated fracture, no previous facial fracture, treatment by open reduction and
      internal fixation using titanium osteosynthesis miniplates, and all case notes
      and radiographs available to study. Sixty-six patients had their fractures
      reduced manually to obtain anatomical reduction without the use of peroperative
      intermaxillary fixation (IMF). Forty-nine were treated conventionally using
      peroperative IMF. The two groups were broadly similar in severity and type of
      fracture, and the method of reduction seemed to be decided by the operator
      according to their preference. IMF was not used routinely postoperatively.
      Overall there were significantly fewer occlusal discrepancies in the early
      postoperative period in those patients treated by anatomical reduction (6/66
      compared with 16/49, P = 0.002) but there was no difference in the final outcome
      of the occlusion between the two methods of reduction. Avoidance of the use of
      peroperative IMF is more economical in time and cost, is safer for the operator,
      and more comfortable for the patient. As this technique produces comparable
      results in the long term with fewer early complications, we conclude that IMF is
      not usually necessary to reduce fractures confined to the mandibular bone.

PMID- 10203224
TI  - Coexisting congenital sublingual dermoid and bronchogenic cyst.
AB  - A congenital dermoid together with a bronchogenic cyst at the base of the tongue
      is extremely rare. We describe a 5-year-old boy who presented with an enlarged
      anterior segment of mandible, slight swelling of the left submandibular region,
      and a large swelling of the floor of the mouth that was displacing the tongue
      posteriorly. Both cysts were successfully excised and the boy made an
      uncomplicated recovery. Occlusion and mastication returned to normal and his
      speech improved remarkably.

PMID- 10203225
TI  - Pharyngeal thyroid: a case report.
AB  - A 48-year-old woman presented with dysphagia. On examination of the pharynx, a
      mass was visible behind and adjacent to the right tonsil. It was excised and
      proved to be ectopic thyroid tissue.

PMID- 10203226
TI  - Malignant myoepithelioma of the salivary glands: clinicopathological and
      immunohistochemical features.
AB  - Malignant myoepitheliomas (myoepithelial carcinomas) are uncommon, and we know of
      only 29 reported cases. We present a new case together with its clinical,
      histological, and immunohistochemical features. The tumour was located in the
      inferior vestibular sulcus of a 64-year-old woman. She was treated by wide local
      resection. Malignant myoepitheliomas are distinguished from benign myoepithelial
      neoplasms by their infiltrating and destructive growth. The tumour cells may be
      spindle-shaped or more rounded (plasmacytoid cells) and contain cellular
      pleomorphism and mitotic activity. The clinical and biological behaviour of this
      tumour is not yet known and there is little information about treatment and
      prognosis.

PMID- 10203227
TI  - Salivary duct carcinoma in the mandible: report of a case with
      immunohistochemical studies.
AB  - Salivary duct carcinoma is rare. We describe a 56-year-old man who developed
      salivary duct carcinoma in the mandible 10 years after removal of the right
      second and third molars. The tumour originated in the retromolar gland or the
      ectopic minor salivary gland in the mandible. The panoramic radiograph showed a
      radiolucent, poorly circumscribed area about 40 x 30 mm in size and distal to the
      lower right first molar. This tooth, together with all neoplastic tissue, was
      removed, and histopathological examination showed it to be a salivary duct
      carcinoma in the mandible. On immunohistochemical staining, keratin antibodies
      stained the ductal structure, 1A4 antibody stained myoepithelial cells, but S-100
      protein and vimentin were not seen. The patient was well and with no sign with
      recurrence 6 years postoperatively.

PMID- 10203228
TI  - Skull reconstruction with a two-part interlocking custom-made titanium plate.
AB  - We have used a two-part interlocking titanium plate for cranioplasty in two
      patients with large skull defects in which reconstruction with a titanium plate
      was required and extensive contouring of the plate was necessary.

PMID- 10203229
TI  - AAOMS/BAOMS scientific meeting: 1999. American Association of Oral and
      Maxillofacial Surgeons. British Association of Oral and Maxillofacial Surgeons.

PMID- 10203230
TI  - Re: Dammer R et al. Conservative or radical treatment of keratocysts: a
      retrospective review. Br J Oral Maxillofac Surg 1997; 35: 46-48.

PMID- 10203231
TI  - Save Your Face Week.

PMID- 10203232
TI  - Re: Guerrero CA, Bell WH, Constasti GI, Rodriguez AM. Mandibular widening by
      intraoral distraction osteogenesis.

PMID- 10203233
TI  - Rosa alio nomine (a rose by any other name)

PMID- 10203234
TI  - Capsaicin pretreatment does not alter rat urinary bladder motor responses induced
      by a kinin B1 receptor agonist after endotoxin treatment.
AB  - The kinin B1 receptor is generally expressed after inflammation or tissue injury.
      Kinin B1 receptor stimulation induces excitatory motor responses in the urinary
      bladder and, in this preparation, the effect of many excitatory transmitters
      involves the stimulation of capsaicin-sensitive afferent nerves. In this study we
      have investigated the effect of capsaicin pretreatment on the bladder
      contractions induced by [Sar0, D-Phe8, des-Arg9]bradykinin (SDABK), a kinin B1
      receptor agonist, by inducing the expression of B1 receptors via the intravesical
      administration of a bacterial endotoxin (LPS, 1 mg/ml) in urethane-anaesthetized
      rats. Three and half hours after LPS, the bladder was filled with saline until
      the micturition reflex was evoked, then 0.15 ml of saline was withdrawn, in order
      to avoid spontaneous reflex contractions. In LPS-pretreated rats the threshold
      volume for micturition was lower than in the control group (248 +/- 44 vs. 534 +/
      112 microl). After capsaicin pretreatment the bladder capacity was increased in
      both control and LPS-treated groups and the LPS-induced hyperreflexia was
      abolished (threshold volumes: 901 +/- 96 vs. 837 +/- 120 microl, respectively).
      The administration of SDABK (30 nmol/kg i.v., 4 h after LPS or saline
      application) produced a local, low amplitude tonic contraction (< 15 mmHg) or a
      tonic contraction with superimposed high amplitude (> or = 15 mmHg) reflex
      contractions but no effect of LPS or capsaicin pretreatment was observed in the
      incidence of these responses. The amplitude of the local response was increased
      by LPS treatment (1.4 +/- 0.3 vs. 4.0 +/- 0.7 mmHg) but capsaicin pretreatment
      did not modify this effect (2.3 +/- 0.4 vs. 4.3 +/- 0.6 mmHg). Likewise, the
      number of reflex contractions induced by SDABK was increased after LPS treatment
      (1.1 +/- 0.4 vs. 2.7 +/- 0.5) irrespective of capsaicin pretreatment (1.3 +/- 0.4
      vs. 2.8 +/- 0.6). These results indicate that: (1) topical application of LPS
      induces a bladder hyperreflexia that is sensitive to capsaicin pretreatment; (2)
      B1 receptor-mediated motor responses (either reflex or local) are enhanced after
      LPS treatment; (3) capsaicin pretreatment does not modify B1 receptor-mediated
      motor response (either reflex or local).

PMID- 10203235
TI  - Insulin-induced hypoglycemia increases preprohypocretin (orexin) mRNA in the rat
      lateral hypothalamic area.
AB  - The recent identification of two peptides named hypocretins (Hcrt), and expressed
      in neurons of the rat tuberal lateral hypothalamus (LHA) previously detected by
      an ovine prolactin antiserum, led us to revisit some experimental procedures
      intented to understand the physiological roles of these neurons. In the present
      study, rats received intraperitoneal injections of insulin and/or glucose.
      Immunocytochemical observations and quantitation of in situ hybridization signals
      pointed out a clear stimulation of Hcrt neurons following the sole injection of
      insulin in hypoglycemic but not in hyperglycemic conditions. This result,
      together with the robust appetite boosting effect of Hcrt reported elsewhere,
      suggests the involvement of Hcrt neurons in the control of food intake.

PMID- 10203236
TI  - Quinolinic acid lesion of the nigrostriatal pathway: effect on turning behaviour
      and protection by elevation of endogenous kynurenic acid in Rattus norvegicus.
AB  - Endogenous excitotoxins have been implicated in degeneration of nigral
      dopaminergic neurons in Parkinson's disease. It may be possible to reduce
      neurodegeneration by blocking the effects of these endogenous agents. The present
      study shows that contralateral turning seen following quinolinic acid-induced
      lesions of the nigrostriatal dopaminergic pathway was reversed by a treatment
      that increased brain levels of kynurenic acid, an endogenous excitatory amino
      acid antagonist. The treatment consisted of nicotinylalanine (5.6 nmol/5 microl
      i.c.v.), an inhibitor of kynureninase and kynurenine hydroxylase plus the
      precursor kynurenine (450 mg/kg i.p.) plus probenencid (200 mg/kg i.p.), an
      inhibitor of organic acid transport. Thus, neuroprotection by increasing brain
      kynurenic acid in vivo may be useful in retarding cell loss in Parkinson's and
      other neurodegenerative diseases involving excitotoxicity.

PMID- 10203237
TI  - Sex-specific expression of N-methyl D-aspartate receptor (NMDAR) in the preoptic
      area of neonatal rats.
AB  - The relationship between the N-methyl-D-aspartate receptor (NMDAR) and the sex
      specific neurotoxicity of L-glutamate on the preoptic area (POA) of neonatal rats
      was studied. The NMDAR were semiquantified by western blot analysis. The kinetic
      change of intracellular calcium and lactate dehydrogenase (LDH) efflux were
      monitored as rapid and delayed toxic signals, respectively. The results showed
      that: (1) the NMDAR expression in POA of male rat is higher than that of females;
      (2) the L-glutamate (500 microM) induced a more significant elevation of
      intracellular calcium in neuron derived from male rat than that from female; (3)
      after glutamate-treatment, the LDH efflux in neuronal culture of male rat is
      higher than that of females. These results suggest that the quantitative
      difference in NMDAR between male and female rats may contribute to the sex
      specific neurotoxicity of L-glutamate on the POA of neonatal rats.

PMID- 10203238
TI  - Olfactory bulbectomy increases vasopressin, but not corticotropin-releasing
      hormone, content in the external layer of the median eminence of male rats.
AB  - Removal of the olfactory bulbs results in numerous physiological and behavioral
      changes in rats. The most frequent and characteristic change is an abnormally
      high level of corticosterone in the blood, possibly due to changes in the
      activity of the hypothalamic neurons which synthesize corticotrophin-releasing
      hormone (CRH). Some of these neurons also synthesize vasopressin (AVP). They are
      located in the parvocellular part of the paraventricular nucleus of the
      hypothalamus, which projects into the external layer of the median eminence. We
      investigated whether there was such a change in activity by studying the
      synthesis and storage activity of CRH neurons in bulbectomized rats. CRH and AVP
      axon terminals in frozen sections of the external layer of the median eminence
      were labeled by immunofluorescence techniques and the degree of labeling was
      analyzed semi quantitatively. There was no difference in the area or intensity of
      CRH-labeling in control and bulbectomized rats. However, a significantly larger
      area was stained for AVP in the bulbectomized than in control rats. We also used
      in situ hybridization, with single- and double-labeling, to study the effects of
      bulbectomy on expression of the genes encoding CRH and AVP. No significant
      difference was found in the levels of mRNA for CRH and the number of CRH+/AVP+
      cell bodies was similar in the parvocellular part of the paraventricular nucleus
      in bulbectomized and normal rats. Our results suggest that the hypothalamo
      pituitary-adrenal (HPA) axis changes observed after olfactory bulbectomy may be
      due to plastic changes in hypothalamic CRH neurons, resulting in greater storage
      of increased AVP in CRH neurosecretory nerve terminals in the external layer of
      the median eminence.

PMID- 10203239
TI  - Hypoxia induces c-Fos protein expression in NMDA but not AMPA glutamate receptor
      labeled neurons within the nucleus tractus solitarii of the conscious rat.
AB  - Glutamatergic transmission within the nucleus tractus solitarii (nTS) is critical
      to full expression of hypoxia-induced cardiorespiratory responses in the rat. To
      further examine the role of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy
      5-methyl-4-isoxazolepropionate (AMPA) glutamate receptors in these responses,
      double-labeling studies of immunoreactivity for c-Fos protein and either NMDA
      (NR1) or AMPA (mGluR2/3) receptor expression were conducted in normoxic rats and
      in hypoxic rats receiving vehicle, MK801, or NBQX. Hypoxia markedly increased c
      Fos immunoreactivity within nTS neurons which in the vast majority co-labeled for
      NMDA. Furthermore, MK801 markedly attenuated such responses. In contrast, co
      localization of AMPA and c-Fos occurred in only a small proportion of neurons,
      and NBQX failed to modify hypoxia-induced c-Fos enhancements. These data suggest
      a predominant role for NMDA but not for AMPA glutamate receptors in nTS mediated
      components of the hypoxic response.

PMID- 10203240
TI  - Arginine vasotocin activates phosphoinositide signal transduction system and
      potentiates N-acetyltransferase activity in the rat pineal gland.
AB  - The pineal gland is innervated by pinealopetal peptidergic fibers originating in
      the hypothalamic nuclei which release arginine vasopressin (AVP) and arginine
      vasotocin (AVT) from their endings. Since the mechanism of AVT action on the
      pineal signal transduction and melatonin synthesis has not been determined so
      far, we examined the effect of AVT on the phosphoinositide signalling system and
      the N-acetyltransferase (NAT) activity in the rat pineal gland. The effect of AVP
      4-9 fragment and AVP analogue desmopressin was also tested. The phosphoinositide
      signalling system was studied by measuring 32P labelling of phosphatidylinositol
      (PI), phosphatidylinositol phosphate (PIP) and phosphatidylinositol bisphosphate
      (PIP2) which reflects PI cycle activation. AVT (10(-5) and 10(-4) M) induced a
      significant increase in 32P labelling of PI, PIP and PIP2. The AVT mediated
      activation of the PI signal cascade was supressed by the vasopressin V1 receptor
      antagonist. The desmopressin and AVP 4-9 fragment were without the effect on PI
      signalling. To assess the AVT role in the melatonin synthesis we studied the
      daily pattern of the pineal NAT activity in rats treated by AVT (10 microg/100 g
      b.w). AVT application in the dark period of the day significantly increased
      nocturnal NAT activity. It can be summarized that AVT activates PI signalling
      system and potentiates NAT activity in the rat pineal gland.

PMID- 10203241
TI  - Gabapentin prevents hyperalgesia during the formalin test in diabetic rats.
AB  - The anticonvulsant agent gabapentin exhibits antihyperalgesic properties in
      animal models of neuropathic pain. Diabetic rats display increased nocifensive
      behavior during the formalin test of persistent chemical irritation to the paw,
      suggesting the presence of abnormal pain processing mechanisms. We therefore,
      investigated the efficacy of gabapentin on formalin-evoked behavior in diabetic
      rats. Diabetic rats showed increased (P < 0.05) flinching during the normally
      quiescent phase of the 5.0% formalin test. Gabapentin (50 mg/kg i.p. 30 min pre
      test) suppressed flinching during phases 1 and 2 of the formalin test in both
      control and diabetic rats but not the increased flinching of diabetic rats during
      the quiescent phase. When 0.5% formalin was used, diabetic rats exhibited
      increased flinching during both the quiescent phase and phase 2. Gabapentin was
      without effect in controls but suppressed (P < 0.01) the increased flinching in
      diabetic rats. Gabapentin displays efficacy against abnormal sensory processing
      in diabetic rats and may be of benefit for treating painful diabetic neuropathy.

PMID- 10203242
TI  - Ferrous iron modulates quinolinate-mediated [3H]MK-801 binding to rat brain
      synaptic membranes in the presence of glycine and spermidine.
AB  - Quinolinic acid (QUIN) displaced binding of agonist and antagonist ligands for
      the N-methyl-D-aspartate (NMDA) receptor in rat brain synaptic membranes. Both
      QUIN and glutamic acid (GLU) potentiated binding of [3H]dizocilpine (MK-801) in
      the presence of glycine (GLY) alone, whereas the potentiation by QUIN was in a
      bell-shaped fashion in contrast to that by GLU. However, further addition of
      spermidine (SPD) induced bell-shaped potentiation by GLU as well as QUIN. The
      potentiation by QUIN was markedly deteriorated by the further addition of FeCl2
      irrespective of the presence of GLY and SPD added. These results suggest that
      QUIN may potentiate [3H]MK-801 binding to the open NMDA channel in rat brain
      synaptic membranes through a mechanism different from that underlying the
      potentiation by GLU.

PMID- 10203243
TI  - Divalent cations modulate glutamate receptors in retinal horizontal cells of the
      perch (Perca fluviatilis).
AB  - Divalent cations had two effects on concentration-response relations of glutamate
      induced membrane currents recorded from retinal horizontal cells. The first
      effect was a reduction of maximum currents. Barium, magnesium, cobalt, nickel and
      an increased calcium concentration caused reductions of maximum currents between
      14% and 70%. The second effect of divalent cations was related to the dopamine
      dependent modulation of glutamate receptors in horizontal cells. The dopamine
      dependent enhancement of glutamate gated currents requires the presence of
      divalent cations besides calcium in the extracellular solution. Without such
      divalent cations application of dopamine caused no increase of the maximum
      currents induced by glutamate, and only a slight shift of the half maximal
      saturation concentration was observed. Addition of magnesium or barium cations in
      millimolar concentration was sufficient to completely restore the dopamine
      dependent modulation.

PMID- 10203244
TI  - Adaptive changes of serotonin 5-HT2A receptors in mice lacking the serotonin
      transporter.
AB  - The serotonin transporter (5-HTT) plays a key-role in the control of
      serotoninergic neurotransmission and is the target of some antidepressants.
      Possible adaptive changes in brain 5-HT2A receptors were investigated in knock
      out mice that do not express the 5-HTT. Autoradiographic labeling of these
      receptors by the selective antagonist [3H]MDL 100,907 and saturation experiments
      with cortical membranes revealed: (1) a new localization of these receptors in
      the external field of striatum (possibly in striosomes); (2) regional variations
      in adaptive changes in the density of 5-HT2A receptors in 5-HT(-/-) mutants (-30
      40% in the claustrum, cerebral cortex and lateral striatum; no significant change
      in the striatum core) as compared to wild-type mice.

PMID- 10203245
TI  - Cerebral neurons express interleukin-6 after transient forebrain ischemia in
      gerbils.
AB  - Markedly increased interleukin-6 (IL-6) mRNA levels occur in experimental
      cerebral ischemia, although the protein production and cellular sources of IL-6
      remain unclear. We examined the cellular localization of IL-6 protein in gerbil
      brain following transient forebrain ischemia employing immunohistochemistry and
      Western blot analysis. The ischemia/recirculation groups revealed distinct IL-6
      immunoreactivity predominantly in cortical and hippocampal neurons after 3 hours
      to 3 days recirculation. At 12 h recirculation, the IL-6 expression declined
      specifically in the hippocampus CA1. Microglia, but not activated astrocytes,
      also expressed IL-6 immunoreactivity. The sham group showed no apparent
      immunoreactivity. IL-6 protein may thus be expressed mainly in neurons following
      transient forebrain ischemia. Its transient decline in the CA1 at 12 h
      recirculation could reflect the specific vulnerability of this region.

PMID- 10203246
TI  - Inward and outward rectifying potassium currents set membrane potentials in
      activated rat microglia.
AB  - Activation of cultured rat microglial cells with lipopolysaccharide (LPS),
      induced outward rectifying K+ (K(V)) current in addition to already existing
      inward rectifying K+ current (K(IR)). By measuring zero-current membrane
      potentials using whole-cell patch-clamp method, we showed that K(V) current plays
      a direct role in setting membrane potential to near -45 mV. Since the membrane
      potentials of microglia show two prominent peaks at -45 and -70 mV, we
      hypothesize that K(IR) current might set the membrane potential to near -70 mV.
      We observed that cells with larger K(IR) current had a zero-current membrane
      potential at around -70 mV, and that blocking of K(IR) current with Ba2+
      depolarized membrane potentials to near -45 mV. These results indicate that the
      amounts of K(IR), and K(V) current determine the zero-current membrane-potentials
      in LPS-activated microglia.

PMID- 10203247
TI  - Reflex effects from leptin sensors in the white adipose tissue of the epididymis
      to the efferent activity of the sympathetic and vagus nerve in the rat.
AB  - Efferent nerve signals were recorded from the central cut end of the small nerve
      filament dissected from the sympathetic nerve innervating the white adipose
      tissue (WAT) of epididymis, inter scapular brown adipose tissue (BAT), pancreas,
      liver, adrenal medulla, and vagus nerve innnervating the pancreas and liver.
      Injection of leptin (2 ng, 0.2 ml) into the white adipose tissue of the either
      side of the epididymis evoked reflex activation of the sympathetic nerve activity
      and suppression in vagus nerve activity. These observations suggest that leptin
      sensors in the white adipose tissue of the epididymis play a role in reflex
      regulation of metabolic functions of the body through the modulatory change in
      sympathetic and vagal outflow.

PMID- 10203248
TI  - Activators of peroxisome proliferator-activated receptor-gamma (PPARgamma)
      inhibit inducible nitric oxide synthase expression but increase heme oxygenase-1
      expression in rat glial cells.
AB  - The peroxisome proliferator-activated receptor-gamma (PPARgamma) is activated by
      15-deoxy-delta(12,14) prostaglandin J2 (15d-PGJ2), anti-diabetic
      thiazolidinediones and several non-steroidal anti-inflammatory drugs (NSAIDs). In
      rat glial cells, lipopolysaccharide and interferon-gamma (LPS/IFN-gamma) induced
      expression of both inducible nitric oxide synthase (iNOS) and heme oxygenase-1
      (HO-1). PPARgamma activators inhibited iNOS expression by LPS and IFN-gamma.
      However, PPARgamma activator alone induced HO-1 expression and further enhanced
      LPS/IFN-gamma-induced HO-1 expression. These results suggest that activation of
      PPARgamma negatively regulate iNOS expression and positively regulates HO-1
      expression in glial cells.

PMID- 10203249
TI  - Abnormal increase in the corticomotor output to the affected hand during
      repetitive transcranial magnetic stimulation of the primary motor cortex in
      patients with writer's cramp.
AB  - In fourteen right-handed patients with writer's cramp and 10 right-handed
      controls, 10 trains of suprathreshold 1 Hz repetitive transcranial magnetic
      stimulation (rTMS) were applied over the left primary motor hand area. Each rTMS
      train lasted for a minute with an intertrain interval of 10 s. The motor evoked
      potentials (MEPs) were recorded from the relaxed contralateral first dorsal
      interosseus muscle. The mean MEP area of each rTMS train was taken as a measure
      of the corticospinal motor output to the affected hand. While the mean MEP area
      decreased significantly in controls, patients showed a significant increase in
      mean MEP area during rTMS. The differential effect on MEP size was highly
      significant. The abnormal rTMS-associated facilitation of the corticomotor output
      to the affected hand demonstrates an increased excitability of the corticospinal
      motor system in writer's cramp.

PMID- 10203250
TI  - No association between the alpha-2 macroglobulin I1000V polymorphism and
      Alzheimer's disease.
AB  - Recent reports have suggested that variability in the alpha2-macroglobulin gene
      is a genetic risk factor for Alzheimer's disease. Here we have both tested a
      common polymorphism in the gene (I1000V) for association with the disease in a
      four-site case control study design, and tested the locus for linkage in a large
      series of sibpairs afflicted with late onset disease. Our results fail to show an
      association between this polymorphism and disease.

PMID- 10203251
TI  - Frequency of HLA-A and B alleles in early and late-onset Alzheimer's disease.
AB  - The frequency of various allele types of the class I Major Histocompatibility
      Complex (MHC) genes HLA-A and HLA-B were compared between pathologically
      confirmed groups of late and early-onset Alzheimer's disease (AD) and a control
      group. DNA was extracted from frozen brain tissue and the highly polymorphic
      second and third exons of the HLA-A and HLA-B genes were independently PCR
      amplified using specific primers. Individual allele types were identified using
      sequence-specific oligonucleotide probes. The results showed that the main
      frequency differences occurred between the late-onset AD and the control group
      however none of these reached statistical significance.

PMID- 10203252
TI  - Effects of the acute and chronic restraint stresses on the central histaminergic
      neuron system of Fischer rat.
AB  - The effects of acute and chronic restraint stresses on the brain histamine level
      and histamine N-methyltransferase activity in Fischer rat brain were studied. The
      acute restraint stress increased the histamine levels in the diencephalon and
      nucleus accumbens, and increased the histamine N-methyltransferase activities in
      the nucleus accumbens and striatum. The chronic restraint stress also increased
      histamine N-methyltransferase activities in the nucleus accumbens and striatum.
      These results indicate that the acute and chronic restraint stresses increase the
      brain histamine turnover, which may partly relate to the vulnerability for stress
      induced anxiety and depression.

PMID- 10203253
TI  - Effects of EGF and TGFbeta1 on c-myc gene expression and DNA synthesis in
      embryonic hamster palate mesenchymal cells.
AB  - Previous work has shown that cell proliferation is a major contributor to the
      early palate morphogenesis in mammals. The present study was undertaken to
      examine the effect of EGF, TGFbeta1 and their combination on proliferation
      (measured by DNA synthesis) and on the expression of a growth related proto
      oncogene, c-myc, in embryonic hamster palate mesenchymal cells (HPMC). Vertically
      developing hamster palatal shelves were dissected on day 11 of gestation, and
      trypsinized, and primary cultures were grown in DMEM + 10% serum at 37 degrees C
      and 5% CO2. Following appropriate growth factor treatment of HPMC, DNA synthesis
      was measured by scintillation counting and extracted RNA was subjected to
      Northern blot analysis. In serum-starved, pre-confuent cultures treated with EGF
      (20 ng/ml), DNA synthesis was stimulated in the presence of 2.5% serum. In
      contrast, treatment of HPMC with TGFbeta1 (10 ng/ml) in the presence or absence
      of EGF/serum for 24 hr, or HPMC pre-treatment with TGFbeta1 (30 min) followed by
      EGF/serum (24 hr), resulted in an arrest of DNA synthesis. Northern blot analysis
      of RNA extracted from HPMC showed that as serum-starved, growth-arrested cells
      progressed through G0 to G1 phase of the cell cycle, following EGF treatment, c
      myc was expressed by 1 hr and declined thereafter. In contrast, TGFbeta1 did not
      support expression of c-myc. Following pre- or co-treatment with TGFbeta1, the
      EGF +/- serum-induced expression of c-myc was seen between 1 and 6 hr. It appears
      that EGF-induced expression of c-myc may be involved in advancing the HPMC in G1,
      and thus may contribute to the onset of DNA synthesis in HPMC. Since co- or pre
      treatment with TGFbeta1 did not inhibit EGF/serum induced expression of c-myc, it
      is possible that growth arresting effect of TGFbeta1 may not be exerted directly
      through inhibition or blockage of c-myc expression.

PMID- 10203254
TI  - Histochemical studies of glycosaminoglycans in developing periodontal ligaments
      of ICR mice.
AB  - Although the periodontal ligament (PL) contains an abundance of
      glycosaminoglycans (GAGs), there are only a few histochemical studies describing
      GAGs in the developing PL. In the present study, the relationship between the
      formation of principal fibers and the molecular species of GAGs in the developing
      PL was examined by light microscopic histochemistry. Jcl:ICR mice were killed on
      day 0 to day 28 after birth. Paraffin-embedded tissue sections were routinely
      made and stained with hematoxylin-eosin (H&E), Azan, or the sensitized high iron
      diamine (S-HID) procedure combined with enzyme digestions. Before tooth eruption,
      thin threads of collagen fibers in the PL assembled and constructed principal
      fibers, which projected from both the side of the alveolar bone and the root of
      the tooth. After tooth eruption, the principal fibers from both sides were
      tightly entangled. In the developing PL, the molecular species of GAGs was mainly
      dermatan sulfate. Moreover, the relative amount of dermatan sulfate increased
      together with the maturation of the principal fibers, while the principal fibers
      adjacent to the alveolar bone and cementum contained chondroitin sulfate. These
      results suggest that dermatan sulfate contributes to collagen fiber assembly in
      the PL and that chondroitin sulfate relates to PL adhesion to the alveolar bone
      and to the cementum of the root.

PMID- 10203255
TI  - New evidence from Le Moustier 1: computer-assisted reconstruction and morphometry
      of the skull.
AB  - In this study, we present a new computerized reconstruction of the Le Moustier 1
      Neanderthal skull and discuss its significance for Neanderthal growth and
      variability. Because of the precarious state of preservation of the original
      material, we applied entirely noninvasive methods of fossil reconstruction and
      morphometry, using a combination of computed tomography, computer graphics, and
      stereolithography. After electronic restoration, the isolated original pieces
      were recomposed on the computer screen using external and internal anatomical
      clues to position the bone fragments and mirror images to complete missing parts.
      The inferred effects of general compressive deformation that occurred during
      fossilization were corrected by virtual decompression of the skull. The resulting
      new reconstruction of the Le Moustier 1 skull shows morphologic features close to
      the typical Neanderthal adult state. Residual asymmetry of skeletal parts can be
      traced to in vivo skeletal modification: the left mandibular joint shows signs of
      a healed condylar fracture, and the anatomy of the occipital region suggests mild
      plagiocephaly. Using micro-CT analysis, the left incus could be recovered from
      the matrix filling of the middle ear cavity. Its morphometric dimensions are
      similar to those of the La Ferrassie III incus. The morphometric characteristics
      of the inner ear deviate substantially from the condition reported as typical for
      Neanderthals and fall within the range of modern human variability.

PMID- 10203256
TI  - Cerebellar afferents from neurons in the extraocular motor nuclei: a fluorescent
      retrograde double-labeling study in the sheep.
AB  - The fluorescent retrograde double labeling technique has been used to identify
      within the extraocular motor nuclei of the sheep the neurons projecting to the
      cerebellum and to provide evidence whether they are motor neurons sending
      collaterals to the cerebellum or a separate population of neurons. The study was
      performed on eight sheep. The fluorescent tracers used were Fast Blue and the
      diamidino yellow dihydrochloride. In one and the same animal a fluorescent tracer
      was injected into the extraocular muscles (EOMs) and the other into bilateral
      points of the vermal folia II-V and paramedian lobule, or into the vermal folia
      VI, VIIA and VIIB, or into the underlying fastigial nuclei. Within the
      oculomotor, trochlear, and abducens nuclei, almost all of the motor neurons were
      labeled by the tracer injected into the EOMs and only a few cells were
      fluorescent for the tracer infiltrated into the cerebellum. These latter
      labelings were present bilaterally, and their number and distribution did not
      show apparent differences after injecting the paramedian lobule and the vermal
      folia or the fastigial nucleus. Along the rostrocaudal extent of the oculomotor
      and trochlear nuclei, the neurons projecting to the cerebellum were intermingled
      with the motor neurons located in the nuclear area facing the medial longitudinal
      fasciculus. In the abducens nucleus they were restricted to the caudal pole of
      the nucleus, which is located ventrolaterally to the genu of the facial nerve.
      Double-labeled neurons were never found. The absence of double-labeled cells, in
      spite of the efficiency of the tracer infiltration into the EOMs and into the
      cerebellum, demonstrates that the cerebellar projections from the extraocular
      motor nuclei are not collaterals of the motor neurons, but axons of a separate
      population of neurons.

PMID- 10203257
TI  - Morphology of the feeding system in agamid lizards: ecological correlates.
AB  - The interaction of organismal design with ecology, and its evolutionary
      development are the subject of many functional and ecomorphological studies. Many
      studies have shown that the morphology and mechanics of the masticatory apparatus
      in mammals are adapted to diet. To investigate the relations between diet and the
      morphological and physiological properties of the lizard jaw system, a detailed
      analysis of the structure of the jaw apparatus was undertaken in the
      insectivorous lizard Plocederma stellio and in closely related herbivorous
      lizards of the genus Uromastix. The morphological and physiological properties of
      the jaw system in P. stellio and U. aegyptius were studied by means of
      dissections, light microscopy, histochemical characterisations, and in vivo
      stimulation experiments. The skull of Uromastix seems to be built for forceful
      biting (high, short snout). Additionally, the pterygoid muscle is modified in P.
      stellio, resulting in an additional force component during static biting.
      Stimulation experiments indicate that jaw muscles in both species are fast, which
      is supported by histochemical stainings. However, the oxidative capacity of the
      jaw muscles is larger in Uromastix. Contraction characteristics and performance
      of the feeding system (force output) are clearly thermally dependent. We conclude
      that several characteristics of the jaw system (presence of extra portion of the
      pterygoid muscle, large oxidative capacity of jaw muscles) in Uromastix may be
      attributed to its herbivorous diet. Jaw muscles, however, are still faster than
      expected. This is presumably the result of trade-offs between the thermal
      characteristics of the jaw adductors and the herbivorous lifestyle of these
      animals.

PMID- 10203258
TI  - Postnatal differentiation of the ductus deferens, tail of the epididymis, and
      distal body of the epididymis in goats occurs independently of rete testis fluid.
AB  - Observations from extratesticular rete-ligated, mature goats indicated that
      epithelial morphology in the tail of the epididymis can be maintained without any
      input from testicular fluid (Goyal et al., Acta Anat., 1994;150: 127-135). Hence,
      the objective of this study was to determine whether the tail of the epididymis
      and/or other regions of the male excurrent ducts can differentiate prior to the
      appearance of lumen in the seminiferous tubules, which is an indicator for the
      onset of seminiferous tubular fluid secretion. Based on age and scrotal
      circumference (SC), 20 male goats were divided into four groups of five animals
      each: 1-4 weeks (SC, 6.5-7.5 cm), 7-10 weeks (SC, 8.5-11.0 cm), 12-15 weeks (SC,
      11.0-14.0 cm), and 15-25 weeks (SC, 16.0-19.0 cm). Tissues were collected from
      the testis, six regions of the epididymis (proximal, middle and distal head;
      proximal and distal body; and tail), and the ductus deferens, and were processed
      for light and electron microscopic examination. Changes in epithelial height and
      cytological features associated with absorption (microvilli, pinocytotic and
      coated vesicles) and protein secretion (RER, Golgi body) were used as markers for
      differentiation. Differentiation of all of these features was comparable to that
      observed in the 15-25-week-old animals in the ductus deferens by > or = 1 week,
      in the tail of the epididymis by > or = 7 weeks, in the distal body of the
      epididymis by > or = 12 weeks, and in the proximal body of the epididymis and all
      three regions of the head of the epididymis by > or = 15 weeks. Seminiferous
      tubules developed lumens between 12 and 15 weeks. In conclusion, epithelial
      differentiation in the ductus deferens, tail of the epididymis, and distal body
      of the epididymis follows a time-dependent, spatial, ascending order and is
      achieved before lumen formation in the seminiferous tubules. Conversely,
      epithelial differentiation in all three regions of the head and the proximal body
      of the epididymis occurs simultaneously and after lumen formation in the
      seminiferous tubules.

PMID- 10203259
TI  - Long-term regeneration of fast and slow murine skeletal muscles after induced
      injury by ACL myotoxin isolated from Agkistrodon contortrix laticinctus (broad
      banded copperhead) venom.
AB  - The aim of the present work was to analyze the regenerated muscle types I and II
      fibers of the soleus and gastrocnemius muscles of mice, 8 months after damage
      induced by ACL myotoxin (ACLMT). Animals received 5 mg/kg of ACLMT into the
      subcutaneous lateral region of the right hind limb, near the Achilles tendon;
      contralateral muscles received saline. Longitudinal and cross sections (10
      microm) of frozen muscle tissue were evaluated. Eight months after ACLMT
      injection, both muscle types I and II fibers of soleus and gastrocnemius muscles
      still showed centralized nuclei and small regenerated fibers. Compared with the
      left muscle, the incidence of type I fibers increased in the right muscle (21% +/
      03% versus 12% +/- 06%, P = 0.009), whereas type II fibers decreased (78% +/-
      02% versus 88% +/- 06%, P = 0.01). The incidence of type IIC fibers was normal.
      These results confirm that ACLMT induced muscle type fiber transformation from
      type II to type I, through type IIC. The area analysis of types I and II fibers
      of the gastrocnemius revealed that injured right muscles have a higher percentage
      of small fibers in both types I and II fibers (0-1,500 microm2) than left
      muscles, which have larger normal type I and II fibers (1,500-3,500 microm2).
      These results indicate that ACLMT can be used as an excellent model to study the
      rearrangement of motor units and the transformation of muscle fiber types during
      regeneration.

PMID- 10203260
TI  - Mitochondrial cristae diversity in human Leydig cells: a revised look at cristae
      morphology in these steroid-producing cells.
AB  - Mitochondria of steroid-producing cells are integrally involved with
      steroidogenesis. For decades, the mitochondrial morphology of Leydig cells, as
      with other steroid-producing cells, has been known to differ from typical
      mitochondria in that the cristae are predominately "tubular." In a few species,
      humans being one example, the cristae have often been further categorized as
      "tubular and/or lamellar," without further elaboration. In the present study,
      mitochondria of human Leydig cells were examined with the purpose of providing a
      more detailed description of "cristae" morphology in these steroid-producing
      cells. The cristae are found to be rather diverse in morphology, consisting of
      elements of anastomosing tubules in continuity with small cisternal regions as
      well as with stacked arrays of lamellae, referred to as "lamellar associations."
      The tubular elements are found to branch in a tripartite fashion and sometimes to
      expand into small cisternal elements at these junctures. The lamellar
      associations are a distinctive feature of cristae in human Leydig cells and
      consist of two to eight closely apposed lamellae with a consistent gap of
      approximately 4 nm between the membranes of apposing lamellae. Such a close
      association of cellular membranes is highly suggestive of an integral
      transmembrane linkage. Although the lamellar associations often appear isolated,
      evidence is present of a continuity of this compartment of the cristae with the
      tubular elements. The connections (termed "initial segments") of the various
      forms of the cristae to the inner mitochondrial membrane are typically via
      tubules. Mitochondria exhibiting a central region of matrix delineated by one or
      more cup-shaped lamellae are also present. The pleomorphic structure of
      mitochondrial cristae in human Leydig cells reemphasizes our present lack of
      knowledge of how subcellular structure relates to steroidogenesis.

PMID- 10203261
TI  - Role of the Botzinger complex in fastigial nucleus-mediated respiratory
      responses.
AB  - We have reported that the phrenic neurogram (PN) is modulated by stimulation of
      the fastigial nucleus (FN) of the cerebellum. The present study was undertaken to
      search for brainstem site(s) involved in the FN efferent pathway to modulate
      phrenic nerve activities. Experiments were performed on 35 anesthetized,
      paralyzed, and ventilated cats, using the PN as the index of the respiratory
      motor output. Results showed that bilateral electrolytic lesions of the red
      nucleus (RN), the paramedian reticular nucleus (PRN), or the pontine respiratory
      group (PRG) had little effect on the ability of FN stimulation to modulate the
      respiratory output. However, the modulation was abolished by bilateral
      electrolytic lesions of the Botzinger complex (BotC). Further studies showed that
      bilateral chemical inactivation of BotC neurons produced by topical
      microinjection of kainic acid or cobalt chloride failed to abolish the
      modulation. We concluded that fibers of passage, not synapses or cell bodies in
      the BotC, were involved in the modulatory effect of FN stimulation on the PN. The
      RN, PRN, and PRG appear not to be important in the neural circuitry responsible
      for the FN modulation of the phrenic activity.

PMID- 10203262
TI  - Distribution of the low-affinity neurotrophin receptor (p75) in the developing
      trigeminal brainstem complex in the rat.
AB  - The low-affinity neurotrophin receptor (p75) binds all members of the
      neurotrophin family. In the rat, during the first week postpartum, dense p75
      immunoreactivity (IR) is present throughout all components of the trigeminal
      brainstem complex (TBC), largely associated with primary sensory afferents.
      Within subnucleus caudalis (SpC) of the TBC, intense p75-IR is present in all
      laminae at birth. During the second and third postnatal weeks, p75-IR in SpC
      gradually fades within the deeper laminae, becoming generally restricted in the
      adult to laminae I and II. Similar declines in p75-IR intensity occur in the
      subnucleus oralis (SpO); in the SpO in the adult, p75-IR is confined to the
      dorsalmost portion of SpO. In subnucleus interpolaris, an emerging, vibrissa
      related pattern of p75-IR is detectable on PD0 (first 24 hr postpartum), which
      becomes fully differentiated during PD4-PD7. However, this pattern gradually
      disappears during the third postnatal week. Ventrally in the nucleus principalis
      (PrV), a pattern of p75-IR that mirrors the topographical arrangement of the
      vibrissae is detectable by PD0-PD1, is fully differentiated by the end of the
      first postnatal week, and persists into adulthood. Perinatal unilateral
      sectioning of the infraorbital nerve on PD0-PD1, but not as late as PD4, disrupts
      p75-IR patterning in the adult PrV. Although p75 appears to be associated with
      primary afferent pattern formation, to determine whether it is essential, we
      examined mutant mice unable to form functional p75. In the TBC of these knockout
      mice, examined as adults, patterns of cytochrome oxidase staining (which parallel
      those of p75-IR) appeared to be normal. In summary, during early development, p75
      is widely expressed in the TBC during periods of active synaptogenesis and
      pattern formation, whereas in the adult, its expression is restricted to
      association with populations of primary sensory afferents. However, the absence
      of functional p75 in genetically altered mice does not appear to prevent primary
      afferent pattern formation.

PMID- 10203263
TI  - Adjuvant breast cancer therapy: current status and future strategies--growth
      kinetics and the improved drug therapy of breast cancer.
AB  - It is well-established that the adjuvant treatment of breast cancer is effective
      in prolonging both disease-free and overall survival. The pressing questions are
      how to improve on existing treatment, whether new agents should be incorporated
      into adjuvant regimens, and, if so, how they should best be utilized. The
      application of log-kill principles to the sigmoid growth curve characteristic of
      human cancers suggests that the chances of eradicating tumor will be increased by
      dose-dense schedules. If the tumor is composed of several cell lines with
      different sensitivities, the optimum therapy is likely to consist of several
      drugs given in sequence at a good dose and on a dense schedule. Such sequential
      chemotherapy, rather than the use of drugs given in combination at longer
      intervals, should maximize log-kill at the same time as minimizing tumor
      regrowth. There is now evidence that the actions of chemotherapy may involve Ras,
      tyrosine kinases (epidermal growth factor receptor, HER2), TC21, or similar
      molecules. This concept may provide important clues for optimizing the clinical
      applications of drug therapy and for designing new therapeutic approaches. It
      might also explain the reason why dose density may be more effective than other
      schedules of administration. New blood vessel formation is an obligatory step in
      the establishment of a tumor in its sigmoid growth course and there is evidence
      that taxanes adversely affect this process. Major practical advances in the
      curative drug therapy of cancer should follow the demonstration of better ways to
      maximize cell kill, the development of predictive in vitro methods of selecting
      active agents, the discovery of techniques to minimize both drug resistance and
      host-cell toxicity, and the improved understanding of cancer-stromal interactions
      and their therapeutic perturbation.

PMID- 10203264
TI  - A review of the efficacy and safety of docetaxel as monotherapy in metastatic
      breast cancer.
AB  - To date, although statistically significant, the overall impact of adjuvant
      chemotherapy on the survival of women with nonmetastatic breast cancer has been
      disappointing. Hence, new agents that have shown good activity against metastatic
      disease should be assessed quickly in the adjuvant setting. Docetaxel (Taxotere;
      Rhone-Poulenc Rorer, Antony, France) is one of the most promising drugs that has
      emerged in recent years, with phase II studies in previously untreated metastatic
      breast cancer indicating a high overall response rate of approximately 60%. A
      recent large, randomized comparison demonstrated docetaxel to be superior to
      doxorubicin with regard to response rate, and it is the only agent to have shown
      this superiority. Docetaxel was also tolerated better. A second randomized trial
      in patients who had already failed an anthracycline-containing regimen showed
      that docetaxel-treated patients survived significantly longer than those treated
      with the combination of mitomycin C and vinblastine. The apparent superiority of
      docetaxel over doxorubicin and the lack of complete cross-resistance between
      these drugs, which has been demonstrated in trials involving anthracycline
      resistant patients, suggest a possible future role for docetaxel, either alone or
      in combination with the anthracycline, in earlier stages of metastatic breast
      cancer and indeed in the adjuvant treatment of early stage disease. The
      combination of docetaxel with doxorubicin appears particularly promising in this
      regard and, unlike the doxorubicin/paclitaxel doublet, has not been reported to
      produce clinically significant cardiomyopathy. The high activity of docetaxel
      provides a compelling rationale for its study as a component of adjuvant
      therapies. Investigators in Brussels and Dublin have recently demonstrated the
      feasibility of two candidate adjuvant programs. Large phase II adjuvant trials
      involving docetaxel are now being assessed.

PMID- 10203265
TI  - Review of docetaxel and doxorubicin-based combinations in the management of
      breast cancer: from metastatic to adjuvant setting.
AB  - Considering the efficacy of docetaxel (Taxotere, Rhone-Poulenc Rorer, Antony,
      France) and doxorubicin in advanced breast cancer and their potential noncross
      resistance, two pilot studies of docetaxel/doxorubicin (TA)-based combinations
      were conducted, one being a phase I dose-finding study of TA and the second a
      phase II study of docetaxel/doxorubicin/cyclophosphamide (TAC). The only
      significant toxicity, seen in both trials, was neutropenia and its consequences
      such as febrile neutropenia without significant documented infections.
      Extrahematologic and particularly docetaxel-specific side effects (fluid
      retention) were mild. Particularly noteworthy was the absence of significant
      cardiac toxicity; overall, there was only one case of congestive heart failure
      (1%). In terms of efficacy, response rates in excess of 70% and 80% were noted in
      both studies, even for patients with visceral metastases. Several phase III
      randomized trials using TA or TAC are presently being performed in first-line
      metastatic breast cancer and most importantly in the adjuvant setting to assess
      whether TA-based combinations will change the natural history of breast cancer.

PMID- 10203266
TI  - Combining new agents with anthracyclines in metastatic breast cancer: an overview
      of recent findings.
AB  - Historically, doxorubicin has been the most effective single agent in metastatic
      breast cancer, and the combination of doxorubicin with other active agents (as in
      the 5-fluorouracil/doxorubicin/cyclophosphamide protocol) has improved patient
      outcome. Results from phase II and several recent phase III studies provide
      evidence that new agents are also highly active in the treatment of metastatic
      breast cancer and suggest that they would be active in combination regimens with
      the anthracyclines. In particular, docetaxel (Taxotere; Rhone-Poulenc Rorer,
      Antony, France) has achieved a significantly higher response rate than
      doxorubicin in phase III randomized clinical trials. Studies to date indicate
      that this high response rate is achieved without accompanying cardiotoxicity.
      Several other new agents, notably, paclitaxel, vinorelbine, and gemcitabine, also
      have been evaluated in combination with the anthracyclines.

PMID- 10203267
TI  - What can be expected from the next generation of adjuvant breast cancer
      treatment?
AB  - At present, the adjuvant therapy of breast cancer is the only treatment that
      offers the prospect of cure. However, recent meta-analysis has shown that
      although they are statistically significant, the benefits that accompany existing
      adjuvant chemotherapy or endocrine therapy are modest. Hence, there is a pressing
      need to evaluate the contribution of active new agents such as the taxanes in the
      adjuvant setting. A further challenge is to integrate entirely new treatment
      strategies targeting signal transduction, apoptosis, and angiogenesis with
      existing treatments. Progress also is being made in the identification of
      molecular markers, such as overexpression of the c-erbB2 receptor, which may
      influence the selection of adjuvant therapy to be given to those patients at
      greatest risk from their breast cancer. Success in all these areas requires
      rigorously conducted clinical trials. These will be conducted efficiently and
      rapidly only if there is good collaboration between investigators, such as is now
      being expected from the recently created Breast International Group.

PMID- 10203268
TI  - Recently initiated studies: neoadjuvant treatments in the next century.
AB  - The adjuvant therapy of early breast cancer currently succeeds in eradicating
      micrometastatic disease in a proportion of women at risk of relapse. However,
      much remains to be done to improve its efficacy. Trials that are presently being
      conducted will determine whether increasing the dose density or dose intensity of
      existing agents, or altering their sequencing, will bring greater benefit. A
      further pressing need is for new agents with proven activity in stage IV disease,
      such as docetaxel (Taxotere; Rhone-Poulenc Rorer, Antony, France), to be assessed
      in the adjuvant setting. A phase II study with docetaxel was conducted in the
      neoadjuvant setting in stage III breast cancer patients. Preliminary results on
      33 patients showed an overall response rate of 85% with neoadjuvant docetaxel and
      a manageable safety profile. Based on this encouraging experience and the phase
      II and III docetaxel single-agent and combination studies, the National Surgical
      Adjuvant Breast Project is investigating regimens involving docetaxel before or
      after surgery, and ongoing European trials are assessing the sequencing of dose
      dense doxorubicin and docetaxel before surgery.

PMID- 10203269
TI  - Molecular dosimeters of smoking damage in the lung.

PMID- 10203271
TI  - Endoscopy removal of axillary nodes gains ground abroad, toehold in U.S.

PMID- 10203270
TI  - Insulin-like growth factor-I: a key regulator of human cancer risk?

PMID- 10203272
TI  - Will Spain's first National Cancer Center boost research?

PMID- 10203273
TI  - Bullish sentiment stays (mostly) high for investments in cancer drugs and
      biotechnology.

PMID- 10203274
TI  - Diagnosis, Tibetan style, underlies small herbal study of advanced breast cancer.

PMID- 10203275
TI  - Werner's syndrome: what does an aging syndrome gene reveal about cancer?

PMID- 10203276
TI  - Survivorship group eyes future research goals.

PMID- 10203277
TI  - The emerging p53 gene family.
AB  - Perturbation of p53 protein function is a common, if not universal, finding in
      human cancer. Tumor suppression by p53 is due, at least in part, to its ability
      to activate transcription of certain genes involved in cell cycle control and
      apoptosis (programmed cell death). Two additional members of the mammalian p53
      family, p73 and p51, which is also known as p40, p63, KET, or p73L, were recently
      identified. Both of these proteins share substantial sequence homology with p53
      and can, at least when overproduced, activate p53-responsive promoters and induce
      apoptosis. Nonetheless, data on differences between these proteins and p53 are
      emerging. For example, p73 is not induced by DNA damage and is not targeted for
      inactivation by viral oncoproteins such as simian virus 40 (SV40) T antigen,
      adenovirus E1B 55K, and human papillomavirus E6. In contrast to p53, neither p73
      nor p51 appears to be frequently mutated in human cancers on the basis of the
      limited studies reported to date. Finally, unlike p53, cells produce multiple p73
      and p51 isoforms as a result of alternative splicing, and production of p73 and
      p51 appears to be restricted to certain tissues. Additional studies are required
      to determine the role, if any, that p73 and p51 play in cell growth control and
      carcinogenesis.

PMID- 10203278
TI  - Unknown primary head and neck squamous cell carcinoma: molecular identification
      of the site of origin.
AB  - BACKGROUND: Unknown primary head and neck squamous cell carcinoma (HNSCC)
      presents as a cervical lymph node metastasis without identification of the
      primary tumor, despite thorough diagnostic work-up that includes physical
      examination, computed tomography, esophagoscopy, laryngoscopy, bronchoscopy, and
      multiple surveillance biopsies. We investigated whether the site of origin of the
      primary tumor could be localized in the upper aerodigestive tract mucosa by
      detection of genetic alterations identical to those found in metastatic lesions.
      METHODS: Microsatellite analysis was performed on metastatic tumors obtained from
      18 patients with unknown primary HNSCC. Histologically benign surveillance biopsy
      specimens were also analyzed. Patients were followed up to 13 years with
      continuing surveillance for primary mucosal tumors. Most patients were treated
      with neck dissection followed by radiation therapy to the affected neck and
      ipsilateral Waldeyer's ring. RESULTS: In 10 (55%) of the 18 patients, at least
      one histopathologically benign mucosal biopsy specimen from defined anatomic
      sites (i.e., most likely sites for an occult primary tumor) demonstrated a
      pattern of genetic alterations identical to that present in cervical lymph node
      metastases. One patient harboring genetic alterations in the base of the tongue
      and two patients harboring genetic alterations in a tonsillar fossa subsequently
      developed HNSCC in the identical or adjacent mucosal region; all three of the
      primary head and neck mucosal tumors that eventually appeared between 1 and 13
      years later in these patients had genetic changes identical to those in the
      benign mucosal biopsy specimens and in the metastatic lymph nodes. CONCLUSIONS:
      These data support the hypothesis that histopathologically benign mucosa of the
      upper aerodigestive tract may harbor foci of clonal, preneoplastic cells that are
      genetically related to metastatic HNSCC and that such mucosal sites are the sites
      of origin of unknown primary HNSCC. Microsatellite analysis may represent a
      clinically useful tool for determining such sites.

PMID- 10203279
TI  - Fruit and vegetable intake and incidence of bladder cancer in a male prospective
      cohort.
AB  - BACKGROUND: Previous epidemiologic studies of fruit and vegetable intake and
      bladder cancer risk have yielded inconsistent results, especially with regard to
      the types of fruits and vegetables consumed. We examined total fruit and
      vegetable intake, as well as intakes of subtypes of fruits and vegetables, in
      relation to bladder cancer risk in a large male prospective cohort study.
      METHODS: Two hundred fifty-two cases of incident bladder cancer were diagnosed
      from 1986 through January 31, 1996, among 47,909 men enrolled in the Health
      Professionals Follow-up Study. Each participant in this cohort completed a 131
      item food-frequency questionnaire in 1986 and subsequently in 1990 and 1994. We
      used logistic regression analyses to examine fruit and vegetable intake in
      relation to bladder cancer risk, after adjusting for age, history of cigarette
      smoking, current smoking status, geographic region, total fluid intake, and
      caloric intake. RESULTS: We observed a weak, inverse association that was not
      statistically significant between total fruit and vegetable intake and bladder
      cancer risk. Intake of cruciferous vegetables was inversely associated with risk
      (relative risk = 0.49; 95% confidence interval = 0.32-0.75, for the highest
      category of cruciferous vegetable intake compared with the lowest), but intakes
      of yellow or green leafy vegetables or carotenoid-rich vegetables were not
      associated with risk. Individual cruciferous vegetables, except for coleslaw,
      were all inversely related to bladder cancer risk, but only the associations for
      broccoli and cabbage were statistically significant. CONCLUSIONS: Data from this
      study indicate that high cruciferous vegetable consumption may reduce bladder
      cancer risk, but other vegetables and fruits may not confer appreciable benefits
      against this cancer.

PMID- 10203280
TI  - Early age at smoking initiation and tobacco carcinogen DNA damage in the lung.
AB  - BACKGROUND: DNA adducts formed as a consequence of exposure to tobacco smoke may
      be involved in carcinogenesis, and their presence may indicate a high risk of
      lung cancer. To determine whether DNA adducts can be used as a "dosimeter" for
      cancer risk, we measured the adduct levels in nontumorous lung tissue and blood
      mononuclear cells from patients with lung cancer, and we collected data from the
      patients on their history of smoking. METHODS: We used the 32P-postlabeling assay
      to measure aromatic hydrophobic DNA adducts in nontumorous lung tissue from 143
      patients and in blood mononuclear cells from 54 of these patients. From the
      smoking histories, we identified exposure variables associated with increased DNA
      adduct levels by use of multivariate analyses with negative binomial regression
      models. RESULTS/ CONCLUSIONS: We found statistically significant interactions for
      variables of current and former smoking and for other smoking variables (e.g.,
      pack-years [number of packs smoked per day x years of smoking] or years smoked),
      indicating that the impact of smoking variables on DNA adduct levels may be
      different in current and former smokers. Consequently, our analyses indicate that
      models for current and former smokers should be considered separately. In current
      smokers, recent smoking intensity (cigarettes smoked per day) was the most
      important variable. In former smokers, age at smoking initiation was inversely
      associated with DNA adduct levels. A highly statistically significant correlation
      (r=.77 [Spearman's correlation]; two sided P<.001) was observed between DNA
      adduct levels in blood mononuclear cells and lung tissue. IMPLICATIONS: Our
      results in former smokers suggest that smoking during adolescence may produce
      physiologic changes that lead to increased DNA adduct persistence or that young
      smokers may be markedly susceptible to DNA adduct formation and have higher
      adduct burdens after they quit smoking than those who started smoking later in
      life.

PMID- 10203281
TI  - Prospective study of colorectal cancer risk in men and plasma levels of insulin
      like growth factor (IGF)-I and IGF-binding protein-3.
AB  - BACKGROUND: Insulin-like growth factor-I (IGF-I) is a potent mitogen for normal
      and neoplastic cells, whereas IGF-binding protein-3 (IGFBP-3) inhibits cell
      growth in many experimental systems. Acromegalics, who have abnormally high
      levels of growth hormone and IGF-I, have higher rates of colorectal cancer. We
      therefore examined associations of plasma levels of IGF-I and IGFBP-3 with the
      risk of colorectal cancer in a prospective case-control study nested in the
      Physicians' Health Study. METHODS: Plasma samples were collected at baseline from
      14916 men without diagnosed cancer. IGF-I, IGF-II, and IGFBP-3 were assayed among
      193 men later diagnosed with colorectal cancer during 14 years of follow-up and
      among 318 age- and smoking-matched control subjects. All P values are two-sided.
      RESULTS: IGFBP-3 levels correlated with IGF-I levels (r=.64) and with IGF-II
      levels (r=.90). After controlling for IGFBP-3, age, smoking, body mass index
      (weight in kg/[height in m]2), and alcohol intake, men in the highest quintile
      for IGF-I had an increased risk of colorectal cancer compared with men in the
      lowest quintile (relative risk [RR]=2.51; 95% confidence interval [CI]=1.15-5.46;
      P for trend = .02). After controlling for IGF-I and other covariates, men with
      higher IGFBP-3 had a lower risk (RR=0.28; 95% CI=0.12-0.66; P for trend = .005,
      comparing extreme quintiles). The associations were consistent during the first
      and the second 7-year follow-up intervals and among younger and older men. IGF-II
      was not associated with risk. CONCLUSIONS: Our findings suggest that circulating
      IGF-I and IGFBP-3 are related to future risk of colorectal cancer.

PMID- 10203282
TI  - Comparison of prophylactic oophorectomy specimens from carriers and noncarriers
      of a BRCA1 or BRCA2 gene mutation. United Kingdom Coordinating Committee on
      Cancer Research (UKCCCR) Familial Ovarian Cancer Study Group.
AB  - BACKGROUND: The natural history of ovarian cancer is not well understood and, to
      date, there is conflicting evidence as to whether or not there is a demonstrable
      precursor lesion. Some women at high risk of developing ovarian cancer because of
      their family history elect to have a prophylactic oophorectomy. To determine
      whether or not a recognizable premalignant lesion could be defined in familial
      ovarian carcinogenesis, we reviewed ovarian tissue specimens from women whose
      ovaries were removed prophylactically before gene testing became available and
      who were tested subsequently for BRCA1 or BRCA2 gene mutations. METHODS: We
      analyzed ovarian tissue specimens from 37 women. The specimens were examined for
      the presence of the following four features: inclusion cysts, clefts and
      fissures, ovarian epithelial metaplasia, and the presence of papillae on the
      ovarian surface epithelium. The specimens were also examined closely for the
      presence of dysplasia and occult neoplasia. Furthermore, the occurrence of
      endometriosis and benign ovarian tumors was documented in these women. The
      protein truncation test, nonradioactive single-stranded conformation polymorphism
      analysis, and heteroduplex analysis, followed by DNA sequencing, were used to
      identify BRCA1 or BRCA2 mutations in either blood samples or ovarian tissue
      specimens. RESULTS: Eleven women had inherited a mutated BRCA1 or BRCA2 gene; 26
      women had not. There was no difference between these groups for any of the
      features studied. CONCLUSIONS: Our data suggest that many of the histologic
      "abnormalities" described in "normal" ovaries are, in fact, variations of the
      normal and are not associated with the development of cancer.

PMID- 10203283
TI  - Plasma prolactin levels and subsequent risk of breast cancer in postmenopausal
      women.
AB  - BACKGROUND: In animal studies, prolactin has been found to be important for
      mammary epithelial development and its administration has been shown consistently
      to increase the rate of mammary tumor formation. Previous epidemiologic studies
      of prolactin and breast cancer risk in postmenopausal women have been limited in
      size, and the results have been inconsistent. We conducted a nested case-control
      study within the prospective Nurses' Health Study cohort to better determine the
      relationship between plasma prolactin levels and postmenopausal breast cancer
      risk. METHODS: Blood samples were collected from cohort members during the period
      from 1989 through 1990. Prolactin levels were measured by use of a microparticle
      enzyme immunoassay. Included in this analysis were 306 postmenopausal women who
      were diagnosed with breast cancer after blood donation but before June 1994. One
      or two postmenopausal control subjects were matched per case subject on the basis
      of age, postmenopausal hormone use, and time of day and month of blood
      collection; the study included a total of 448 control subjects. RESULTS: In
      conditional logistic regression analyses, a significant positive association was
      observed between plasma level of prolactin and postmenopausal breast cancer risk
      (highest versus lowest quartile, multivariate relative risk = 2.03; 95%
      confidence interval = 1.24-3.31; two-sided P for trend = .01). The relationship
      was independent of plasma sex steroid hormone levels and was similar after
      excluding case subjects diagnosed in the first 2 years after blood collection.
      CONCLUSIONS: These prospective data suggest that higher plasma prolactin levels
      are associated with an increased risk of breast cancer in postmenopausal women.

PMID- 10203284
TI  - Oral contraceptive use and risk of gestational trophoblastic tumors.
AB  - BACKGROUND: Gestational trophoblastic disease refers to a spectrum of rare benign
      and malignant gynecologic disorders whose pathogenesis is not well understood.
      Recent studies from China and the United States have raised the hypothesis that
      long-term use of oral contraceptives before conception may increase the risk of
      gestational trophoblastic tumors. A multicenter case-control study of gestational
      trophoblastic tumors was undertaken to test this hypothesis. METHODS: Telephone
      interviews were conducted with 235 case patients, including 50 with gestational
      choriocarcinoma, and 413 control subjects matched on recentness of pregnancy, age
      at pregnancy, and area of residence. Relative risks (odds ratios) were computed
      by conditional logistic regression. Reported P values are two-sided. RESULTS: The
      relative risk estimate for ever having used oral contraceptives before the index
      pregnancy was 1.9 (95% confidence interval [CI] = 1.2-3.0), and the risk
      increased with duration of use (P for trend = .05). The estimate was highest for
      women who used oral contraceptives during the cycle in which they became pregnant
      (relative risk = 4.0; 95% CI=1.6-10), but there was no consistent pattern
      according to the time interval since last use. Separate analyses of
      choriocarcinoma and persistent mole yielded similar results, i.e., the relative
      risk estimates for oral contraceptive use were 2.2 (95% CI=0.8-6.4) and 1.8 (95%
      CI=1.0-3.0), respectively. Control for the number of sexual partners, which was
      independently associated with risk (P for trend = .05), did not materially change
      the results. CONCLUSIONS: This study, the largest to date, indicates that long
      duration of oral contraceptive use before conception increases the risk of
      gestational trophoblastic tumors. These findings may provide clues to the
      pathogenesis of this rare disease. Changes in use of oral contraceptives are not
      warranted, however, because the incidence attributable to oral contraceptive use
      is very low.

PMID- 10203286
TI  - Re: Quality of life in advanced prostate cancer: results of a randomized
      therapeutic trial.

PMID- 10203285
TI  - p53 mutation as a genetic trait of typical medullary breast carcinoma.

PMID- 10203287
TI  - Irinotecan-induced central nervous system toxicity: a case report.

PMID- 10203288
TI  - Revisiting: Involuntary smoking and lung cancer: a case-control study.

PMID- 10203289
TI  - Re: Trends in reported incidence of primary malignant brain tumors in children in
      the United States.

PMID- 10203290
TI  - Re: Diagnostic testing following screening mammography in the elderly.

PMID- 10203291
TI  - Re: Hormonal etiology of epithelial ovarian cancer, with a hypothesis concerning
      the role of androgens and progesterone.

PMID- 10203292
TI  - Pregnancy-induced hypertension and insulin resistance: evidence for a connection.
AB  - PIH, the most common complication of pregnancy, remains a major source of
      maternal-child morbidity and mortality. Yet the etiology of this disorder is
      still little understood. There is now a growing body of evidence linking PIH and
      insulin resistance. Both proteinuric and non-proteinuric PIH predict future
      essential hypertension, and to a lesser extent, diabetes, disorders strongly
      related to glucose intolerance and insulin resistance. PIH is associated with
      diabetes, occurring in up to 50% of diabetic pregnancies. PIH is characterized by
      the same features that define IRS, including hypertension, dyslipidemia,
      disruption of endothelial and platelet function and related disturbances of
      prostanoid synthesis, coagulation and fibrinolytic abnormalities, hyperuricemia,
      atherosclerotic changes, and obesity. During the last decade, controlled studies
      by at least 11 different research groups in nine countries have established
      significant positive associations between both proteinuric and nonproteinuric PIH
      and various measures of insulin resistance. In particular, prospective
      investigations by at least five groups of investigators have indicated that
      relative hyperinsulinemia, glucose intolerance, and insulin insensitivity predict
      the subsequent development of PIH. These and other studies suggest that insulin
      resistance may play a causal role in the pathogenesis of PIH, and that some
      aspects of PIH may represent an early manifestation of IRS, precipitated by the
      profound metabolic and hemostatic challenges of gestation.

PMID- 10203293
TI  - In vitro perfusion studies of single umbilical artery cords: the vasoactive
      effects of serotonin.
AB  - BACKGROUND: To investigate the vascular resistance and the vasoactive effects of
      serotonin in arteries from single umbilical artery (SUA) cords. METHODS: The
      preparations were sampled from 10 patients with SUA cords. The control group
      (n=20) was matched according to gestational age, birth weight percentile, blood
      pressure and proteinuria. The arterial segments were perfused in vitro employing
      a constant perfusion rate and measuring alterations in perfusion pressure.
      Following an initial test with serotonin 10(-7) M the drug was administrated in
      stepwise increasing concentrations from 10(-10) to 10(-5) M. RESULTS: The
      vascular resistance was significantly reduced in the SUA group compared to the
      control group (p<0.01). In about half of the preparations in both groups
      serotonin 10(-7) M induced a transient pressure decrease followed by a larger
      pressure increase. The remaining arteries showed a monophasic pressure increase.
      The maximum constrictory response calculated in percent of the prestimulatory
      perfusion pressure was significantly increased (p<0.01) in the SUA compared to
      the control group, but non-significantly increased (p=0.073) when calculated in
      absolute values (mmHg). CONCLUSIONS: Arteries in SUA cords display reduced
      vascular resistance compared to arteries from normal cords in in vitro perfused
      preparations. The response pattern to serotonin was not altered, but the
      constrictory response might be increased in arteries from SUA cords.

PMID- 10203294
TI  - Pelvic relaxation and associated risk factors: the results of logistic regression
      analysis.
AB  - BACKGROUND: To determine the possible risk factors in our population. METHODS:
      From 250 patients attending our clinic 28 patients with pelvic relaxation were
      the study group and the rest, 222 in all, were the control group. RESULTS: Age,
      marriage period, parity and number of abortus in pelvic relaxation group are
      found to be significantly higher with univariate analysis. With logistic
      regression analysis menopause, grandmultiparity, abortus (two or more), home
      deliveries, history of macrosomic infant (4500 gr. or more), deliveries without
      episiotomy and laceration of uterine cervix are found to be risk factors for
      pelvic relaxation. CONCLUSIONS: Good family planning programs to reduce
      grandmultiparity and unnecessary curettage for undesired pregnancies, preventing
      harmful home deliveries by inexperienced people, and fearless usage of episiotomy
      in difficult deliveries are necessary to prevent pelvic relaxation.

PMID- 10203295
TI  - The after breakfast 50-g, 1-hour glucose challenge test in urban Mexican pregnant
      women: its sensitivity and specificity evaluated by three diagnostic criteria for
      gestational diabetes mellitus.
AB  - BACKGROUND: To study the sensitivity and specificity of the 50-g, 1-hour
      gestational glucose challenge test performed 1 to 2 hours after a non
      standardized home breakfast in urban Mexican women by using three different
      gestational diabetes mellitus diagnostic criteria. METHODS: Four hundred and
      forty-five consecutive women of 24-28 weeks gestation were studied. The glucose
      challenge test was performed in the fed state and a week later a fasting 100-g, 3
      hours oral glucose tolerance test was carried out in all of them. Duplicate serum
      glucose concentrations were determined by a glucose-oxidase method. Sensitivity
      and specificity were calculated using three different diagnostic criteria for
      gestational diabetes mellitus. RESULTS: The glucose challenge test performed as
      indicated, with a cutoff of 7.8 mmol/L, had 88-89% sensitivity and 85-87%
      specificity when using as diagnostic criteria those proposed by the National
      Diabetes Data Group and by Carpenter & Coustan; by using Sacks et al. criteria,
      the values were 82% and 88%, respectively. Considering only pregnant women > or =
      25 years of age, the sensitivity increased to 92% with the National Diabetes Data
      Group criteria. Pregnant women < 25 years of age had significantly lower blood
      glucose values than those with age > or = 25 years during the glucose tolerance
      test. CONCLUSIONS: For the general group the sensitivity of the glucose challenge
      test performed 1 to 2 hours after breakfast was similar, based on the National
      Diabetes Data Group and the Carpenter & Coustan's diagnostic criteria for
      gestational diabetes mellitus. However, when pregnant women > or = 25 years of
      age were considered, the use of the former criteria yielded a slightly better
      sensitivity.

PMID- 10203296
TI  - Protein gene product 9.5-immunoreactive nerve fibers and cells in human cervix of
      late pregnant, postpartal and non-pregnant women.
AB  - BACKGROUND: The aim of this study was to examine the occurrence and distribution
      of the general neuronal marker protein gene product (PGP) 9.5 in the cervix
      uteri. METHODS: Cervical biopsies were obtained from late pregnant (n=5),
      postpartal (n=5) and non-pregnant (n=5) women. The samples were prepared for
      immunohistochemistry using antibodies to PGP 9.5. RESULTS: Nerve fibers were
      found consistently in all biopsies. There were differences in the occurrence and
      distribution of PGP 9.5 immunoreactive nerve fibers and cells between the three
      groups. Immunoreactive nerve fibers were observed at a moderate to abundant
      frequency in the stroma and around arterial vessel walls, in all groups.
      Immunoreactive nerve fibers were also observed at high frequency within and
      around glandular epithelium in the late pregnant and postpartal groups. PGP 9.5
      immunoreactive cells were seen occasionally in the stroma of the non-pregnant
      group, but at a high frequency in the stroma, around arterial blood vessel walls,
      around and within the glandular epithelium in the late pregnant and postpartal
      groups. The total frequency of immunoreactive nerve fibers and cells was the
      highest in the late pregnant group, slightly lower in the postpartal group, and
      the lowest in the non-pregnant group. CONCLUSIONS: These findings show that
      changes in the general innervation take place during human cervical ripening
      until late pregnancy and parturition.

PMID- 10203297
TI  - Epidemiological studies of obstetric ultrasound examinations in Denmark 1989-1990
      versus 1994-1995.
AB  - BACKGROUND: The purpose of the study was to describe number, type, time and place
      for all obstetric ultrasound examinations that pregnant women in Denmark had
      performed during their pregnancies. Further, to compare these results with
      results from a similar national survey performed five years previously. METHODS:
      During a two-week period in February 1990 and a two-week period in May 1995, all
      delivery departments in Denmark (1990: 57/1995: 49) participated in two identical
      designed studies with the aim as described above. For all women who delivered in
      these periods variables were recorded from the women's case records and after
      interview. After the exclusion of 108/145 women without complete registrations,
      the material consisted of 2268/2315 women; approximately 3.7%/3.4% of all
      deliveries in Denmark 1990/1995. The chi2 and t-test were used for statistical
      analyses with a statistical significance level of 5%. RESULTS: Of all obstetric
      ultrasound examinations 99%/96% took place in hospitals. Twenty/seven percent of
      the women had no examination during their pregnancies. The mean number of
      obstetric ultrasound examinations was 1.5/1.9 for all women and 1.9/2.1 for women
      who had at least one examination. In total 40%/54% of the women were offered a
      screening examination. Women with an offer of screening had a mean number of
      examinations: 1.8/2.0 and women without an offer: 1.3/1.9 (1990: p<0.05; 1995:
      non-significant). CONCLUSION: The studies have shown an increasing number of
      women with an offer of ultrasound screening and in general an increased use of
      ultrasound examinations in obstetrics during the five year period 1990-1995 in
      Denmark.

PMID- 10203298
TI  - Prevalence of physical and sexual abuse before and during pregnancy among Swedish
      couples.
AB  - BACKGROUND: To estimate the prevalence of threats and actual acts of physical and
      sexual abuse during pregnancy. METHODS: Two hundred and seven pregnant Swedish
      women married to or cohabiting with Swedish men were randomly selected from three
      antenatal clinics in the city of Goteborg, Sweden. A standardized questionnaire
      was used for personal interviews about the women's experience of physical and
      sexual abuse by a husband or a boyfriend at some point in the past, during the
      last year and during current pregnancy. RESULTS: Twenty-seven point five percent
      of the women reported that they had been exposed to physical violence at some
      point in the past by their husband/boyfriend. Twenty-four and a half percent of
      the women had experienced some form of threat, physical or sexual violence during
      the last year. At some time (once or more) during their current pregnancy, the
      proportions of women who had been exposed to the following categories of
      violence, were as follows: 14.5%-symbolic violence, 14.5%-threats of mild
      violence, 2.9%-threats of moderate violence, 2.9%-threats of serious violence,
      11%-mild violence, 4.3%-minor violence, 2.4%-moderate violence, 4.3%-serious
      violence and 3.3%-sexual violence. CONCLUSIONS: This study demonstrates that a
      considerable number of women had experienced threats, physical and sexual abuse
      during pregnancy. There is an obvious need for screening of experience of
      domestic violence among pregnant women to enhance the safety of women and their
      unborn babies.

PMID- 10203299
TI  - Urinary tissue kallikrein excretion in black African women with severe pre
      eclampsia.
AB  - BACKGROUND: A study of tissue kallikrein excretion in African women with severe
      pre-eclampsia. METHODS: Random untimed urine samples were collected from all
      women (n=198) recruited to this study; 66 women with severe pre-eclampsia, 66
      normotensive pregnant women of similar length of gestation and 66 normotensive
      non-pregnant women. Urine specimens were analyzed for urinary tissue kallikrein
      using a selective, synthetic chromogenic tripeptide substrate (S2266) having the
      sequence H-D-Val-Leu-Arg-pNA. RESULTS: Urinary tissue kallikrein levels were
      decreased in women with severe pre-eclampsia compared with those of gestation
      matched normotensive pregnant women at 28 weeks of gestation (1.55+/-0.95 vs.
      3.02+/-1.35 ng TK/microg protein; p<0.0001) and at near delivery date (1.21+/
      0.53 vis. 3.11+/-1.2 ng TK/microg protein; p<0.0001). In the normotensive
      pregnant group, there was no significance difference in urinary tissue kallikrein
      excretion close at delivery date compared to 28 weeks of gestation (3.02+/-1.35
      vs. 3.11+/-1.21 ngTK/microg protein; p=0.23). No statistical difference in
      urinary tissue kallikrein excretion was observed between normotensive pregnant
      and normotensive non pregnant women (3.02+/-1.35 vs. 2.97+/-1.12 ngTK/microg
      protein; p=0.16). Urinary tissue kallikrein excretion correlated positively with
      urinary creatinine levels at 28 weeks of gestation (r=0.69; p<0.0001) and close
      to delivery date (r=0.84; p<0.0001). There was no correlation between neonatal
      birthweight and urinary tissue kallikrein levels (r=-0.44; p=0.41). CONCLUSION:
      The decreased levels of urinary tissue kallikrein excretion in pre-eclamptic
      patients suggests an etiological role for this serine protease in hypertensive
      disorders of pregnancy.

PMID- 10203300
TI  - Frigen II improves the reliability of measurement of interleukin-1 related
      substances in amniotic fluid.
AB  - BACKGROUND: To investigate the role of interleukin-1 related substances in
      amniotic fluid in normal term labor without intrauterine infection. METHODS:
      Amniotic fluid samples were collected from forty-one patients with various
      backgrounds. A novel pre-assay treatment using Frigen II was introduced to
      improve the recovery rates of cytokines, i.e., interleukin-1alpha, interleukin
      1beta and interleukin-1 receptor antagonist, prior to ELISA assay. Urine samples
      from newborn infants were also tested. RESULTS: The concentrations of interleukin
      1alpha, interleukin-1beta and interleukin-1ra were significantly higher in
      samples from normal vaginal delivery. The higher levels of interleukin-1alpha
      were also observed in samples from preterm labor without infection. Preterm
      infants produced more of interleukin-1 receptor antagonist in urine compared with
      term infants. CONCLUSIONS: This study provides evidence of the possible
      involvement of interleukin-1 related substances in labor without signs of
      infection. The data from newborn urine suggests that amniotic interleukin-1ra
      originates from the fetus. However, amniotic fluid interleukin-1alpha and
      interleukin-1beta may be derived from maternal tissue, such as decidua.

PMID- 10203301
TI  - Evaluation of a cut-off value for sperm motility after different hours of
      incubation to select the suitable reproductive technology (IVF or ICSI).
AB  - BACKGROUND: The aim of this study was to enhance the predictability of
      conventional semen parameters for in-vitro fertilization outcome. The utility of
      late sperm motility in presence of a cumulus-oocyte complex after different hours
      of incubation was investigated to predict the outcome of IVF in borderline and
      normal ejaculates (at least 5 x 10(6) motile sperm). METHODS: The study was done
      on 52 infertile couples undergoing conventional in-vitro fertilization and embryo
      transfer. Sperm were prepared by the Percoll cushion centrifugation with swim
      down. Cocultures were established by inseminating the cumulus-oocyte complexes
      with 100000 motile spermatozoa and incubating them for 48 hours. Another 100000
      spermatozoa were incubated in culture medium for 48 hours. Sperm motility (WHO
      a+b) was determined at 0, 4, 24 and 48 hours of incubation. RESULTS: The
      fertilization rate was 65.5% (42.9-88.1). The conventional semen parameters did
      not correlate with the fertilization rate. Sperm motility measured after
      different hours of incubation was found to be significantly positively correlated
      with the fertilizing ability of sperm in vitro in Spearman's rank correlation
      test: motility after 0 h (p<0.02), after 4 h (p=0.0025). after 24 h (n.s.) and
      after 48 h (p=0.0071). Cut-off values for late sperm motility were determined and
      differences in fertilization rates were calculated for these cut-off values after
      different hours of incubation. A cut-off value of 20% progressive motile
      spermatozoa after 48 hours gave the best statistical power (fertilization rate
      71.7 vs. 50.2%, p<0.001). Significant differences in the fertilization rates were
      also observed for a cut-off value of 35% after 24 hours of incubation (70.1 vs.
      46.2%, p=0.001) and for a cut-off point of 60% after 4 hours (72.4 vs. 51.5%,
      p=0.001). CONCLUSIONS: The predictive power of sperm motility after 48 h for
      fertilization outcome provides support in the decision-making process within the
      assisted reproduction setting. If less than 20% of sperm are motile after 48 h
      micromanipulatory techniques should be considered.

PMID- 10203302
TI  - Secular trends in sperm variables for groups of men in fertile and infertile
      couples.
AB  - OBJECTIVE: To assess possible secular trends in sperm variables in men according
      to previous or subsequent paternity. DESIGN: A comparison of secular trends in
      sperm variables 1975-1994 in men under investigation for infertility in groups
      according to previous and subsequent paternity, based on data from the Medical
      Birth Registry of Norway. SETTING: University hospital, Sperm laboratory and the
      Medical Birth Registry of Norway. MATERIAL: Samples were obtained from: 1108 men
      who had fathered at least one child before the analysis. 1786 men who had at
      least one child after the analysis, and 2286 men with no children registered.
      MAIN OUTCOME MEASURES: Sperm concentration, seminal fluid volume, total number of
      spermatozoa per ejaculate. RESULTS: Analyzed by year of evaluation, men with no
      child registered had a significant secular decrease of sperm concentration, total
      number of sperms per ejaculate and seminal volume. The group with subsequent
      children had significant secular decrease of sperm concentration and total sperm
      count per ejaculate, while no significant changes were found for the group with
      previous children. Analyzed by year of birth, a significant decrease of sperm
      concentration and total sperm count was found for the group without and for the
      group with subsequent children. CONCLUSION: The results are compatible with a
      cohort effect, exhibiting a trend of deteriorating sperm variables in consecutive
      birth cohorts.

PMID- 10203303
TI  - DNA strand breaks in human sperm cells: a comparison between men with normal and
      oligozoospermic sperm samples.
AB  - BACKGROUND: The aim of this report was to compare the degree of DNA strand breaks
      in known normal fertile men to those with oligozoospermia, and evaluate the
      presence of DNA strand breaks in normal raw sperm, after Percoll and swim-up and
      following conventional cryopreservation, as all these preparation methods might
      differ in selection of healthy sperm cells. METHODS: Sperm samples from proven
      fertile sperm donors (n=20) and infertile men with oligozoospermia (n=33) were
      tested for the presence of DNA strand breaks in the spermatozoa, by direct
      immunoperoxidase detection of digoxigenin-labeled genomic DNA. A correlation to
      other sperm parameters, sperm counts, motility and Kruger's strict criteria was
      performed. RESULTS: DNA strand breaks were found significantly more often in
      sperm samples from men with oligozoospermia compared to sperm samples of normal
      fertile men. The degree of spermatozoa with DNA strand breaks was correlated
      proportional with the degree of morphological pathological sperm cells judged by
      Kruger's strict criteria. The percentage of spermatozoa with DNA strand breaks in
      the samples was not influenced by procedures such as the swim-up technique,
      Percoll gradients or cryopreservation and thawing. CONCLUSION: DNA strand breaks
      were found significantly more often in men with oligozoospermia compared to
      normospermic men. The DNA strand breaks might play an important role for the
      maturation process of the spermatozoa in the same way as apoptosis is controlling
      the number of early meiotic germ cells in the testis, and hereby play an
      important role in advanced fertility treatments (ICSI).

PMID- 10203304
TI  - GnRH analogue in everyday gynecology: is it possible to rationalize its use?
AB  - BACKGROUND: The study was an audit of patients who attended the Menstrual
      Disorders Clinic at Glasgow Royal Infirmary over a five year period, and received
      gonadotrophin-releasing hormone analog (GnRHa). We aimed to identify the clinical
      indications for the use of GnRHa, and the effect of the latter in terms of
      symptom resolution and ultimate outcome. We aim to use this information to
      formulate a strategy for the use of GnRHa by targeting this expensive therapy to
      those situations where maximum benefit will be achieved. METHODS: A retrospective
      case review analysis of 201 patients. RESULTS: Thirty-eight percent of women
      presented with pelvic pain, 33% with disordered menstruation and 26% with
      premenstrual symptomatology. Overall, 74% of patients reported a beneficial
      effect of GnRHa. In the non-cyclical pelvic pain group, those patients with
      adhesions constituted a much greater proportion of those who did not derive
      benefit from GnRHa than those who did (43% vs. 16%; p<0.05; data not shown). In
      those patients with disordered menses, there was no difference between the
      diagnosis in those who did or did not derive benefit from GnRHa. Also with the
      exception of endometrial preparation prior to ablation and in the correction of
      anemia, the ultimate outcome was no different in the two groups. Of the patients
      with premenstrual symptomatology, the greatest proportion of those deriving
      benefit from GnRHa (41%) ultimately had an operative resolution. CONCLUSIONS: Our
      results enable us to use GnRHa as a first line in those clinical situations where
      maximum benefit will be achieved, either in terms of symptom resolution or as a
      tool to identify the most appropriate therapeutic option. We can therefore
      rationalize our prescribing both to the benefit of the patient and to our budget.

PMID- 10203305
TI  - Pregnancy outcome after laser vaporization of the cervix.
AB  - BACKGROUND: Treatment of cervical intraepithelial neoplasia (CIN) with cold knife
      or CO2-laser conization is associated with obstetrical problems in subsequent
      pregnancies. Little is published about pregnancy outcome after laser vaporization
      of the uterine cervix. The aim of this study was to determine the risk of preterm
      delivery and low birth weight in pregnancies following this kind of treatment.
      METHODS: Two hundred and thirty-six women who during the 11 year period 1982 to
      1992 underwent laser vaporization of the uterine cervix and after treatment gave
      birth were included in this study. For each case two controls matched for parity,
      age (-/+ 3 years) and year of delivery were identified. The material was analyzed
      as a matched cohort study. RESULTS: No relationship was found between laser
      vaporization and preterm delivery or low birth weight. Medial gestational length
      was in both groups 40 weeks (range 3142 weeks among cases and 2842 weeks among
      controls). Mean birth weight was 3428 g (range 1370 to 6130 g) among cases and
      3407 (range 672 to 5470 g) among controls. CONCLUSION: Laser vaporization of the
      uterine cervix does not influence the outcome of subsequent pregnancy.

PMID- 10203306
TI  - Limb necrosis associated with twin-twin transfusion syndrome treated with YAG
      laser coagulation.

PMID- 10203307
TI  - Laparoscopic lateral ovarian transposition before pelvic irradiation for a Non
      Hodgkin lymphoma.

PMID- 10203308
TI  - Rhythmical corticomotor communication.
AB  - Recent non-invasive human studies show that rhythmic oscillatory activity of the
      motor cortex and the firing of motor units of the muscle are coherent during
      isometric contraction, with peak frequencies around 20 Hz or 40 Hz, depending on
      the contraction strength. The cortical signals precede the motor unit firing and
      appear to reflect modulation of the common central drive to the spinal motoneuron
      pool. The rhythmic modulation may form a tool for efficient driving of motor
      units but we express some reservations about the assumed binding and attention
      related roles of the rolandic brain rhythms. The cortex-muscle coherence is of
      interest for understanding of cortical control of voluntary movements and the
      pathophysiology of various motor disorders, as well as for unravelling the
      functional significance of cortical rhythms.

PMID- 10203309
TI  - Changes in the action potential in sensory neurones after peripheral axotomy in
      vivo.
AB  - Following nerve injury, modified somatic ion channels may underlie ectopic
      activity in axotomized A-type neurones in dorsal root ganglia (DRGs) leading to
      abnormal pain signalling. Using intracellular microelectrodes both in vivo and in
      vitro, action potentials (APs) were recorded in rat DRG neurones classified by
      axonal conduction velocity. After lesions to L5 spinal or sciatic nerves, APs in
      both A alpha/beta and A delta cells were wider, and those in A alpha/beta
      neurones more frequently showed inflections during repolarization, than APs in
      cells in undamaged ganglia. AP amplitudes and dV/dt(max) were not significantly
      altered by axotomy. These results confirm previous observations in intact ganglia
      in vitro but differ from those reported for dissociated neurones using patch
      recording techniques.

PMID- 10203310
TI  - Acute cell damage after low Mg2+-induced epileptiform activity in organotypic
      hippocampal slice cultures.
AB  - Upon perfusion with Mg2+-free artificial cerebrospinal fluid (ACSF) organotypic
      hippocampal slice cultures develop seizure-like events and tonic recurrent
      discharges in which areas CA3 and CA1 and, in contrast to acute slices, also the
      dentate gyrus (DG) participate. Using the fluorescent dye propidium iodide (PI)
      we show that sustained epileptic activity causes cell death in the DG and
      pyramidal cell layer particularly evident in the granule cell layer of the DG.
      This correlates with the decrease of the electrophysiological responses to hilar
      stimulation. Interestingly, perfusion with carbogenated serum-free ACSF also
      induces some cell death which is, however, mild compared with low magnesium
      treated slice cultures.

PMID- 10203311
TI  - Effect of articulatory and mental tasks on postural control.
AB  - The present study sought to determine whether the increased postural instability
      produced by a spoken mental task was due to competing demands for attentional
      resources or perturbation of posture by articulation. Postural sway was measured
      in 36 normal subjects under the following conditions: repeating a number aloud
      (articulation), counting backwards aloud in multiples of seven (articulation and
      attention), counting backwards silently (attention), and no mental task (neither
      articulation nor attention). Articulation resulted in a significant increase in
      sway, whereas no effect of attention was observed. We conclude that in order to
      accurately assess the effect of attentional demands on postural control, it is
      important to eliminate or control the effects of articulation.

PMID- 10203313
TI  - High-frequency magnetic oscillations evoked by posterior tibial nerve
      stimulation.
AB  - Magnetocephalographic recordings of the primary somatosensory response (P37m) and
      high-frequency oscillations (HFOs) evoked by posterior tibial nerve stimulation
      were obtained in normal subjects. Electrical stimuli were delivered to the
      posterior tibial nerve and magnetic recordings were taken over the superior
      aspect of the left hemisphere with a 37-channel biomagnetometer. In order to
      separate the high-frequency oscillations from the underlying P37m, the wide-band
      (0.1-1200 Hz) recorded responses were digitally filtered with a 500-800 Hz band
      pass filter. The localization of the HFOs were estimated to be in somatosensory
      area 3b, very close to the P37m source. Our data suggest that the HFOs are
      somatotopically arranged in the primary somatosensory cortex, and are a
      ubiquitous phenomenon of the primary somatosensory cortex.

PMID- 10203312
TI  - Long-term potentiation at excitatory amino acid synapses on midbrain dopamine
      neurons.
AB  - Evidence suggests that a process analogous to long-term potentiation (LTP) may
      underlie the enhanced behavioural responses attending chronic administration of
      amphetamine and cocaine in animals (behavioural sensitization). Augmented
      excitatory amino acid (EAA)-mediated transmission at the level of midbrain
      dopamine neurons has been implicated as a change critical to the development of
      sensitization. Here we provide an initial demonstration that EAA synapses on
      dopamine neurons can undergo plasticity. Tetanic stimulation of the subthalamic
      nucleus induced a long-lasting increase (39.2 +/- 10.4%) in the amplitude of
      excitatory postsynaptic potentials recorded in dopamine neurons of the substantia
      nigra. This LTP, which did not occur in the presence of NMDA antagonists, may
      constitute the mechanism that lies at the heart of sensitization.

PMID- 10203314
TI  - Retraction of muscle afferents from the rat ventral horn during development.
AB  - The postnatal reorganization of rat proprioreceptive muscle afferent spinal
      terminal fields was explored by labelling transganglionically afferents from
      extensor digitorum communis with cholera toxin B sub-unit at different ages.
      Immunocytochemistry revealed labelled afferents in all segments examined (C4-T2)
      as well as retrogradely labelled motoneurones (C5-T1). Dorsal horn innervation
      appeared similar at all ages, but there were striking changes in the ventral
      horn. Many afferent boutons were seen closely apposed to labelled motoneurone
      proximal dendrites at postnatal day 7 (P7) and P14, but in the adult such
      contacts were almost entirely confined to distal dendrites. Between P7 and adult,
      a significant decrease in bouton density was found in the area dorsomedial to the
      labelled motoneurones that contained labelled dendrites and antagonist
      motoneurones. This anatomical reorganization may explain both the increasing
      stretch reflex threshold and its concomitant decrease in magnitude with age, and
      the reduction in excitatory connections to antagonist motoneurones, previously
      described in developmental neurophysiological studies.

PMID- 10203315
TI  - Transplanting the N-terminus from Kv1.4 to Kv1.1 generates an inwardly rectifying
      K+ channel.
AB  - A chimeric channel, 4N/1, was generated from two outwardly rectifying K+ channels
      by linking the N-terminal cytoplasmic domain of hKv1.4 (N terminus ball and chain
      of hKv1.4) with the transmembrane body of hKv1.1 (delta78N1 construct of hKv1.1).
      The recombinant channel has properties similar to the six transmembrane inward
      rectifiers and opens on hyperpolarization with a threshold of activation at -90
      mV. Outward currents are seen on depolarization provided the channel is first
      exposed to a hyperpolarizing pulse of -100 mV or more. Hyperpolarization at and
      beyond -130 mV provides evidence of channel deactivation. Delta78N1 does not show
      inward currents on hyperpolarization but does open on depolarizing from -80 mV
      with characteristics similar to native hKv1.1. The outward currents seen in both
      delta78N1 and 4N/1 inactivate slowly at rates consistent with C-type
      inactivation. The inward rectification of the 4N/1 chimera is consistent with the
      inactivation gating mechanism. This implies that the addition of the N-terminus
      from hKv1.4 to hKv1.1 shifts channel activation to hyperpolarizing potentials.
      These results suggest a mechanism involving the N-terminal cytoplasmic domain for
      conversion of outward rectifiers to inward rectifiers.

PMID- 10203316
TI  - Blockade of NMDA receptors located at the dorsomedial prefrontal cortex impairs
      spatial working memory in rats.
AB  - We investigated the effects of NMDA and muscarinic acetylcholine receptor
      blockade in the rostral part of dorsomedial (dmPFC) and dorsolateral prefrontal
      cortex (dlPFC) on spatial working memory (SWM) (delayed non-matching to position
      task (DNMTP)). The NMDA antagonist, CPP (0.01, 0.03, 0.1 and 0.3
      microg/hemisphere) and the muscarinic antagonist, scopolamine (10
      microg/hemisphere) were locally infused into the brain of male Wistar rats. In
      the mPFC CPP 0.1 microg disrupted SWM delay-dependently and CPP 0.3 microg caused
      a delay-independent performance deficit. Scopolamine disrupted non-cognitive
      performance, but did not affect SWM accuracy. In the dlPFC, scopolamine or lower
      doses of CPP did not affect SWM accuracy, but CPP 0.3 microg disrupted non
      cognitive performance. We concluded that the NMDA receptors in the dmPFC regulate
      SWM processes, whereas the muscarinic receptors in the dmPFC mediate non
      cognitive performance in the DNMTP task.

PMID- 10203317
TI  - Learning to see 3-D: psychophysics and brain electrical activity.
AB  - We investigated human perceptual learning with stereoscopic stimuli presented
      below threshold. Different visual patterns were shown as dynamic random dot
      stereograms in a forced-choice design in order to determine the psychophysical
      thresholds of 16 adults. Brain electrical activity was recorded from 30
      electrodes over parieto-occipital areas while stereograms were presented with
      horizontal disparities below threshold. During the observation of sub-threshold
      stimuli, we tested repeatedly whether implicit perceptual learning occurred. More
      than half of the subjects learned to see stereoscopic targets. This was
      accompanied by topographic changes in the pattern of activation of neural
      assemblies in the visual cortex where the center of activity shifted towards the
      right hemisphere. Subjects who did not improve in perception, displayed no such
      effects.

PMID- 10203318
TI  - Prosopagnosia and structural encoding of faces: evidence from event-related
      potentials.
AB  - Event-related brain potentials (ERPs) were recorded in response to unfamiliar
      faces and to houses from a severely prosopagnosic patient (PHD) and 24 control
      subjects. For all control subjects, faces elicited an enhanced negativity at
      lateral temporal electrodes (N170). This component was absent for PHD. Comparable
      results were obtained in response to inverted faces and houses. A selective
      deficit in face recognition is therefore reflected by abnormalities in ERP
      components specific to faces. As PHD was shown to have substantial deficits on
      tasks requiring the structural analysis of faces, these findings are consistent
      with the view that the N170 reflects processes involved in the structural
      encoding of faces, and may be a measure of selective impairments in the analysis
      of face components.

PMID- 10203319
TI  - Low expression of GluR2 AMPA receptor subunit protein by human motor neurons.
AB  - Disturbance of glutamate neurotransmission may contribute to motor neuron injury
      in amyotrophic lateral sclerosis. There is evidence that human motor neurons may
      express a specific profile of glutamate receptors, with low or absent expression
      of mRNA for the GluR2 AMPA receptor subunit, which has a crucial role in
      controlling calcium permeability. This study, using an immunocytochemical
      approach with a GluR2 specific antibody, shows that human upper and lower motor
      neurons have a very low/absent expression of GluR2 protein, in contrast to many
      other neuronal groups. Thus, it is likely that human motor neurons express a high
      proportion of atypical, calcium permeable AMPA receptors which may contribute to
      selective vulnerability and may allow cell-specific modulation of the actions of
      glutamate.

PMID- 10203320
TI  - Distinctive neuronal organization of the olfactory bulb of the laboratory shrew.
AB  - The organization of the main olfactory bulb of an insectivore, the laboratory
      shrew (Suncus murinus), was studied morphologically. We found particular small
      spherical regions, nidi, at the border between the glomerular and external
      plexiform layer (EPL), which were intensely GAD positive, 30-60 microm in
      diameter, and where no olfactory nerves were seen. Around the nidus small
      calbindin D28k-positive GABAergic neurons, perinidal cells, were clustered.
      Furthermore, a distinctive type of newly discovered neurons, which we named
      tasseled cells, located at the middle of the EPL extended dendrites to the nidus,
      where their small tuft-like complicated branches made synapses with perinidal
      cells. The present study showed that the basic components of the olfactory bulb
      are not necessarily constant in all mammals.

PMID- 10203321
TI  - Cerebrospinal fluid nitric oxide metabolites in painful diseases.
AB  - To elucidate the involvement of NO in pain transmission in humans, we measured NO
      metabolites (nitrite/nitrate) in the CSF of patients with painful diseases using
      an NO analyzer based on the Griess method. The nitrite/nitrate levels in patients
      with degenerative lumbar disease (DLD), but not those with fracture or
      appendicitis, were significantly higher than those in an age-matched control
      group. The duration of pain in the DLD group was much longer than that in the
      fracture or appendicitis group. The nitrite/nitrate levels in the middle-aged and
      elderly DLD patients depended on the duration of pain. These data probably
      suggest that the duration of pain is critical for the elevation in
      nitrite/nitrate levels.

PMID- 10203322
TI  - Changes in sensitivity to stimulus deviance in Alzheimer's disease: an ERP
      perspective.
AB  - The mismatch negativity (MMN) of the event-related brain potential (ERP) reflects
      the storage of information in sensory memory. MMNs were recorded from eight
      patients with Alzheimer's disease (AD) and eight controls to small (delta50 Hz),
      large (delta300 Hz), and a variety of highly deviant, environmental sounds. Both
      old controls and patients showed robust MMNs to all three classes of deviant
      events, and robust P3 compounds (indicative of active attention) to the
      environmental sounds. The data suggest that patients with mild AD have an intact
      sensory memory mechanism that responds similarly to that of controls to
      systematic increases in deviance. However, for both older controls and patients,
      only highly deviant acoustic events are likely to involuntary capture attention.

PMID- 10203323
TI  - Central administration of insulin-like growth factor-1 inhibits
      lipopolysaccharide-induced sickness behavior in mice.
AB  - To assess the possible modulatory effects of insulin-like growth factor-1 (IGF-1)
      on the brain effects of proinflammatory cytokines, male CD-1 mice were injected
      into the lateral ventricle of the brain with a behaviorally depressing dose (100
      ng) of the cytokine inducer lipopolysaccharide (LPS) and their response to
      various doses of IGF-1 (0, 100 and 1000 ng) was measured during behavioral tests
      carried before and at various time intervals after treatment. LPS induced a
      profound behavioral depression that was abrogated by the higher dose of IGF-1
      tested. Since the behavioral effects of LPS are mediated by the local synthesis
      and results of proinflammatory cytokines, these results indicate that IGF-1
      interferes with the production and/or action of proinflammatory cytokines in the
      brain.

PMID- 10203324
TI  - Cortical tuning: a function of anticipated stimulus intensity.
AB  - We investigated the activation of the brain during anticipation of tactile
      stimuli by continuous cerebral blood flow velocity (CBFV) monitoring with
      bilateral transcranial Doppler sonography. A forced choice paradigm was performed
      where a first group of subjects (n=16) was expecting suprathreshold and a second
      group (n=19) was anticipating threshold tactile stimuli to the index finger after
      a cueing tone. During the anticipation of suprathreshold stimuli the CBFV always
      exhibited a significantly stronger increase in the right hemisphere than in the
      left, even when stimuli were anticipated at the right index finger. Conversely
      when stimuli at perception threshold were expected, the respective contralateral
      hemisphere showed a significantly stronger perfusion increase. These data show
      that preparatory activation of the brain during stimulus anticipation is
      dependant on the expected stimulus intensity.

PMID- 10203325
TI  - Nocistatin reverses the effect of orphanin FQ/nociceptin in antagonizing morphine
      analgesia.
AB  - Nocistatin is a recently characterized neuropeptide derived from the
      preprohormone containing nociceptin (Orphanin FQ, OFQ). Nocistatin was reported
      to antagonize OFQ induced allodynia, hyperalgesia and prostaglandin E2-elicited
      pain responses. The aim of the present study was to determine whether nocistatin,
      injected intracerebroventricularly (i.c.v.), would reverse the anti-morphine
      effect of OFQ in rats using the tail-flick latency (TFL) as the nociceptive
      index. I.c.v. injection of nocistatin at doses of 0.005, 0.05, 0.5, 5, 50, and
      500 ng produced no significant changes in the basal TFL, nor did it affect
      morphine analgesia. However, it significantly reversed the antagonistic effect of
      OFQ on morphine analgesia when co-injected i.c.v. at doses of 0.05, 0.5, 5, 50
      and 500 ng per rat with OFQ. The dose-response curve was bell-shaped and the most
      effective dose was 0.5 ng. The results suggest that nocistatin can reverse the
      anti-morphine effect of OFQ in rat brain.

PMID- 10203326
TI  - Topography of the secondary somatosensory cortex in humans: a magnetoencephalo
      graphic study.
AB  - The topography of the secondary somatosensory cortex (SII) responses to
      somatosensory stimulation applied to various parts of the body of normal
      volunteers was analyzed using magnetoencephalography (MEG). Although there were
      large inter-individual differences, the following orders of a location of
      equivalent current dipoles (ECDs) were found; (1) Anterior-posterior direction:
      lower lip-upper lip-thumb-middle finger-foot, (2) Medial-lateral direction: foot
      middle finger-thumb-upper lip-lower lip, and (3) Lower-upper direction: lower lip
      upper-lip-thumb-middle finger-foot. In general, these findings are similar to
      those obtained in studies of monkeys. However, the differentiation was not as
      clear as that seen in the homunculus in the primary somatosensory cortex (SI).
      The auditory cortex is located at a site more posterior, lateral and lower than
      the SII.

PMID- 10203327
TI  - Retrogradely transported CTB-saporin kills sympathetic preganglionic neurons.
AB  - Aiming to ablate sympathetic preganglionic neurons (SPN) innervating a defined
      target, we injected saporin conjugated to cholera toxin B subunit (CTB)
      unilaterally into the superior cervical ganglion of rats. In spinal cord segments
      T1-T3, the numbers of cholinergic neurons in the intermediolateral cell column
      ipsilateral and contralateral to the injected ganglion were significantly
      different by 3 days post-injection. By day 14, 77% of ipsilateral cholinergic
      neurons had disappeared. A higher percentage of neurons were killed in T1-T2 than
      in T3. Comparing SPN counts from CTB-saporin injected rats and counts from rats
      receiving unconjugated CTB into the superior cervical ganglion indicated that 84%
      of SPN supplying the ganglion had died by 14 days. Retrogradely transported CTB
      saporin kills sympathetic preganglionic neurons and may also eliminate other
      types of neurons that transport CTB.

PMID- 10203329
TI  - Visual background motion reduces size distortion in spatial neglect.
AB  - Patients with visual neglect show deficits in horizontal size perception in their
      neglected hemispace, as previously reported. The present study examined whether
      this size distortion can be modulated by visual background motion to the left or
      right while the patient performs a visual size judgment task. Six neglect
      patients and six normal subjects were investigated with a psychophysical size
      judgment task. All neglect patients showed a significant perceptual
      underestimation of horizontal bars in their left hemispace expressed as an
      overestimation of horizontal object size in the baseline (no motion) condition.
      Slow visual motion of background stimuli towards the right, ipsilesional side
      aggravated the deficit slightly, but not significantly, whereas leftward
      background motion completely normalized the size distortion (in four cases) or
      even led to an overcompensation (in two cases). This facilitatory effect was
      specific as it was obvious for the constant errors in the size judgments, but not
      in their accuracy as reflected by unchanged difference thresholds. These results
      suggest that coherent background motion restores temporarily the disturbed
      perception and representation of horizontal object size in spatial neglect.

PMID- 10203328
TI  - Neither L-NAME nor L-arginine changes extracellular glutamate elevation and
      anoxic depolarization during global ischemia and reperfusion in rat.
AB  - Both the rise in extracellular glutamate concentration and anoxic depolarization
      in the rat striatum during 15 min of global ischemia and reperfusion were
      monitored using glutamate biosensor and direct current potential electrodes,
      respectively. Cerebral blood flow (CBF) was simultaneously monitored with a
      glutamate biosensor or a direct current potential electrode. Before the onset of
      ischemia, treatment with N(G)-nitro-L-arginine methyl ester hydrochloride (L
      NAME) decreased CBF, while L-arginine increased CBF. However, neither L-NAME nor
      L-arginine significantly changed CBF during ischemia and reperfusion compared
      with vehicle-treated animals. The time-course and extracellular glutamate
      concentration increase during ischemia and reperfusion among L-NAME-, L-arginine-
      and vehicle-treated animals were very similar. These results were strengthened by
      the time-course and amplitude of anoxic depolarization. The study suggests that
      NO is not an important mediator of glutamate release during ischemia and
      reperfusion.

PMID- 10203330
TI  - Cerebro-cerebellar functional connectivity revealed by the laterality index in
      tool-use learning.
AB  - The function of the lateral part of the human cerebellum was investigated through
      cerebro-cerebellar functional connectivity. We propose a laterality index method
      to reveal a functional and possibly anatomical pathway between the cerebral
      cortex and the cerebellum. The brain activity involved in learning a visually
      guided tracking skill using a novel computer mouse was measured by functional
      magnetic resonance imaging. The imaging data analyzed using the method suggest
      that the simple lobule and semilunar lobule of the lateral cerebellum have
      connections with the pars opercularis and pars triangularis in the inferior
      frontal gyrus. A possible function of this cerebro-cerebellar communication loop
      is tool usage, which is in-between the cognitive and motor functions of the human
      cerebellum.

PMID- 10203331
TI  - Handedness in opposite and same-sex dizygotic twins: testing the testosterone
      hypothesis.
AB  - Prenatal exposure to testosterone is proposed to promote development of the right
      hemisphere and increase the incidence of sinistrality. This proposition was
      tested by comparing the hand preference of 59 opposite-sex and 61 same-sex
      dizygotic twins. Because testosterone is thought to pass between twins in utero,
      it was predicted that females with a male twin would show a high incidence of
      sinistrality compared to females with a female twin. Similarly, it was predicted
      that males with a male twin would be more likely to be sinistral than males with
      a female twin. Measures of the strength of hand preference and the incidence of
      sinistrality revealed no difference between the opposite and same-sex twins for
      either sex. The data also failed to confirm reports that first-born twins are
      more likely to be sinistral than second-born twins. These data add to a growing
      body of research which is critical of the testosterone hypothesis.

PMID- 10203332
TI  - Focal hippocampal gain of NGF function elicits specific septal cholinergic
      reorganization.
AB  - The influence of NGF on the neuroanatomic substrate(s) subserving learning and
      memory was probed by somatic mosaic analysis. NGF XAT mice underwent unilateral
      hippocampal delivery of virus vector expressing cre recombinase to produce focal
      NGF gain of function mosaics. Activated mice expressing increased NGF, but not
      control mice transduced with the lacZ gene showed reorganization of the
      septohippocampal projection assessed by retrograde labeling with Fluorogold (FG).
      Mice mosaic for NGF function demonstrated in ipsilateral medial septum and
      diagonal band significant increases in FG-labeled cell bodies (94%), ChAT-labeled
      cells (55%), double-positive cells (190%) and increased somal size of double
      positive cells (56%) than did non-activated mice. These results indicate that
      reorganization of the cholinergic septal input to a specific hippocampal region
      is promoted by gain of NGF function.

PMID- 10203333
TI  - Expression and modulation of matrix metalloproteinase-2 and tissue inhibitors of
      metalloproteinases in human embryonic CNS stem cells.
AB  - The expression and regulation of matrix metalloproteinases (MMPs) and tissue
      inhibitors of MMPs (TIMPs) in neuroectodermal precursor cells is undocumented. We
      report the presence of MMP-2, but no MMP-9, and of all the four known TIMPs in
      neuroepithelial stem cells isolated from the human CNS. The expression of TIMP-1,
      TIMP-2 and TIMP-3 was unchanged following stem cells differentiation into neurons
      and glia. In contrast, while MMP-2 and TIMP-4 were localized to both stem and
      mature CNS cells, their levels of expression were substantially reduced in the
      latter. TIMP-4 showed a 23-fold reduction in media conditioned by differentiated
      cells compared with stem cell-conditioned media, reflecting a 6-fold decrease in
      mRNA expression. Interestingly, TIMP-4 also differed from the other TIMPs in that
      it was cell-associated in the stem cells, where this fraction remained unchanged
      upon differentiation. Hence, regulation of selective MMPs and TIMPs occurs during
      differentiation of human neural precursors suggesting that MMP-2 and TIMP-4 in
      particular may perform regulatory roles in the developing CNS.

PMID- 10203334
TI  - Cyclosporin A limits calcium-induced axonal damage following traumatic brain
      injury.
AB  - In traumatic axonal injury, Ca2+ influx across a focally damaged axolemma
      precipitates local mitochondrial failure, degradation of the subaxolemmal
      spectrin network and compaction of neurofilaments, which collectively contribute
      to axonal failure. In previous studies, cyclosporin A pretreatment preserved
      mitochondrial integrity and attenuated axonal failure following trauma. Here we
      investigate whether this CsA-linked protection was related to the concomitant
      blunting of intra-axonal, Ca2+-induced cytoskeletal changes in traumatic axonal
      injury, assessed with antibodies targeting spectrin proteolysis and neurofilament
      compaction. CsA pretreatment dramatically reduced Ca2+-induced cytoskeletal
      damage following injury; CsA-treated rats, compared with vehicle-treated rats,
      displayed a 70% decrease in immunoreactive/damaged profiles. We suggest that CsA
      mediated preservation of mitochondrial integrity enables the restoration of ionic
      and metabolic homeostasis thereby short-circuiting Ca2+-induced proteolysis in
      injured axons.

PMID- 10203335
TI  - CCK-8 can inhibit ingestive behavior by acting on the liver.
AB  - The possibility that cholecystokinin octapeptide (CCK-8) can inhibit ingestive
      behavior by acting on the liver was investigated. Male rats were trained to
      ingest an intraorally infused 1 M solution of sucrose and then injected with 10
      microg CCK-8/kg. Intraperitoneal or hepatic portal vein, but not jugular vein,
      injection suppressed intake of the sucrose solution. Intraperitoneal injection
      was more potent than hepatic portal vein injection. Inhibition by hepatic portal
      vein injection was blocked by i.p. injection of 80 microg/kg of the CCK-A
      receptor antagonist L-364,718 or by hepatic vagotomy. The results support the
      hypothesis that CCK-8 can inhibit ingestive behavior via a hormonal action on the
      liver.

PMID- 10203336
TI  - Calcium signals in cell lines derived from the cerebral cortex of normal and
      trisomy 16 mice.
AB  - We established two immortalized cell lines from cerebral cortex of normal (CNh)
      and trisomy 16 (CTb) mouse fetuses, an animal model of human trisomy 21. Those
      cells loaded with the fluorescent Ca2+ dyes, Indo-1 and Fluo-3, exhibited
      increments of intracellular Ca2+ ([Ca2+]i) in response to external glutamate,
      NMDA, AMPA and kainate. CTb cells exhibited higher basal Ca2+ concentrations and
      had higher amplitude and slower time-dependent kinetics in the decay than CNh
      cells, suggesting an impaired Ca2+ buffering capacity in the trisomy 16-derived
      cell line. Nicotine also induced increments of [Ca2+]i. The CTb cell line could
      represent a model for studying cellular alterations related to Down syndrome.

PMID- 10203337
TI  - Neuroprotective effects of acetylsalicylic acid in an animal model of focal brain
      ischemia.
AB  - Recent studies have shown neuroprotective effects of acetylsalicylic acid (ASA)
      in cell cultures and hippocampal slices. The present study demonstrates similar
      effects in a whole-animal modal of focal ischemic stroke. Focal cortical ischemia
      was produced in Wistar rats by ligation of the common carotid and middle cerebral
      arteries. Subjects were sacrificed 8 days after ligation, and infarct volume was
      assessed via automated densitometry. Significant reductions in infarct volume
      were seen with i.p. ASA doses of 15 mg/kg and above. Reductions occurred when ASA
      was injected 2 h or 30 min before ligation, but not when it was injected 8 or 24
      h before, or 30 min after ligation.

PMID- 10203338
TI  - Functional organisation of the field-L-complex of adult male zebra finches.
AB  - Functional maps of auditory response areas were established from multiunit
      recordings in the caudal telencephalon of male zebra finches. The response
      criterion was a difference of activity from the spontaneous discharge level. Pure
      tones and conspecific song were used as stimuli. The auditory part of the caudal
      telencephalon in zebra finches can be subdivided into six functionally separated
      centres. The definition of separate areas is based on the existence of tonotopic
      gradients in each single area and on differences in neural response behaviour
      between areas. The anatomical area L2a is functionally subdivided into two
      tonotopic centres. Other areas can be identified by anatomy and function. The
      borders vary slightly depending on the description method.

PMID- 10203339
TI  - Up-regulation of class A Ca2+ channels in trigeminal ganglion after pulp
      exposure.
AB  - We have studied changes in the level of calcium channel expression in the cell
      bodies of neurons located in the maxillary division of the trigeminal ganglion
      following induction of persistent pulpitis by pulp exposure in the right
      maxillary molars. Using anti-peptide antibodies to the alpha1 subunit of class A
      (P-/Q-type) voltage-gated calcium channels, we observed slight increases in the
      expression level three days following surgery and approximately 4 fold increase
      by eight days following the lesion. These changes in the expression of the alpha1
      subunit of class A calcium channels may have functional implications in the
      responses of nociceptive neurons to chronic inflammation.

PMID- 10203340
TI  - Grating and plaid chrominance motion influences the suppressed ocular following
      response.
AB  - Involuntary eye movements to foveal stimulation were measured in a monkey while
      it performed a fixation task. Second-order plaid motion generated higher
      velocities of eye movements than did first-order gratings, yet the latency of the
      early following response was no different for grating or plaid motion.
      Nevertheless, early suppressed ocular following responses to isoluminant motion
      continue to be titrated by stimulus velocity and spatial frequency. Motion
      defined by 60% luminance contrast gratings and plaids generated a motion signal
      gain of 60% over chrominance motion. The 20% longer latency of eye movements to
      chrominance motion may reflect the longer conduction latency of the parvocellular
      channel and an additional stage in cortical processing en route to motion areas
      and eye movement control.

PMID- 10203341
TI  - Neurons in the temporal cortex changed their preferred direction of motion
      dependent on shape.
AB  - To investigate neuronal mechanisms that integrate different visual modalities
      such as motion and shape, neuronal activities in the superior temporal
      polysensory area (STP) were recorded from monkeys that were watching rotating
      images. In total, 194 neurons were identified as visually responsive. Of these,
      73 neurons (38%) showed differential response depending on both shape and
      direction of motion (MS neurons). Of these 73 neurons, 21 (29%) were identified
      as reversal type MS neurons (MSr neurons), that is, they responded to an opposite
      preferred direction when the shape was different. The results confirm that
      neurons in the STP can be simultaneously activated by different attributes of
      visual stimuli. The data also suggest that individual STP neurons can process
      more than one type of visual stimulus.

PMID- 10203342
TI  - Impaired apoptosis in mitogen-stimulated lymphocytes of patients with multiple
      sclerosis.
AB  - We investigated the sensitivity to cell death of peripheral blood mononuclear
      cells (PBMCs) from patients with multiple sclerosis (MS). PBMCs from MS patients,
      following PHA stimulation, were less sensitive to cell death than those from
      healthy donors (mean +/- s.e.m., 22.5 +/- 1.9 in MS patients vs 36.5 +/- 2.8 in
      healthy controls; p = 0.0003). However, when Fas-agonist antibody was added, the
      increase in respect to apoptosis induced by mitogen alone was even higher in MS
      patients than in controls. In addition, PHA-activated PBMCs from MS patients
      showed higher surface expression of Fas than controls, while Bcl-2 expression was
      decreased. This finding raised the question of whether an impaired generation of
      apoptotic signals may be contributing to the immune component of MS.

PMID- 10203343
TI  - Time course of narrow frequency bands in the waking EEG during sleep deprivation.
AB  - Electroencephalograms (EEGs) of 14 normal subjects were recorded every 2 h during
      38 h constant routines. Adjacent narrow frequency bands (NFB) with similar
      temporal trends were grouped into frequency clusters. Clusters I (2.00-7.75 Hz)
      and III (11.00-14.75 Hz) exhibited similar time courses which may reflect both
      the duration of time awake and a circadian modulation. Cluster II (8.00-10.75 Hz)
      was characterized by a time course similar to the circadian modulation of core
      body temperature. Cluster V (18.00-24.75 Hz) was correlated with subjective
      sleepiness and may reflect the increasing effort made by subjects to perform the
      task as sleep deprivation lengthened. Various NFB in the waking EEG may reflect
      different physiological mechanisms underlying variations in vigilance states.

PMID- 10203344
TI  - Interleukin-6 and its soluble receptor in serum and cerebrospinal fluid after
      cerebral trauma.
AB  - Interleukin-6 (IL-6) and its soluble receptor (sIL-6-R) were measured in
      cerebrospinal fluid (CSF) and serum of 11 severely head injured patients for up
      to 3 weeks following trauma. IL-6 increased immediately after injury displaying
      much higher concentrations in CSF than in serum (n = 11). Differently, median
      levels of sIL-6-R remained in the normal ranges being 10 times higher in serum
      than in CSF. However, increased amounts over control levels were found in CSF (n
      = 7) and intrathecal release of sIL-6-R was also suggested (n = 7). Although no
      correlation with the extent of cerebral lesion or with clinical outcome was
      evident, elevation of sIL-6-R in CSF supports a pivotal role for IL-6/sIL-6-R
      complex in the injured brain.

PMID- 10203345
TI  - Fos-like immunoreactivity in the periaqueductal gray of rats exposed to a natural
      predator.
AB  - In the present study we examined, in rats exposed to a predator (cat), the
      distribution of neurons expressing Fos along the continuum formed by the central
      gray surrounding the caudal pole of the third ventricle and the periaqueductal
      gray (PAG). After the predatory encounter, a distinct cluster of Fos
      immunoreactive cells was observed in the precommissural nucleus. In the rostral
      two-thirds of the PAG, Fos expression was mostly seen in the dorsomedial and
      dorsolateral regions. In contrast, at caudal levels of the PAG, most of the Fos
      labelled neurons were distributed in the lateral and ventrolateral PAG. These
      results are discussed and compared with the pattern of the PAG activation after
      fear conditioned to a context or elicited by aversive foot shock.

PMID- 10203346
TI  - Expression of CNTF in Muller cells of the rat retina after pressure-induced
      ischemia.
AB  - We have investigated the expression and cellular localization of ciliary
      neurotrophic factor (CNTF) in the rat retina following ischemia induced by
      transiently increasing the intraocular pressure. In the normal retina, CNTF
      immunoreactivity was restricted to profiles in the ganglion cell layer. Following
      ischemia and reperfusion, immunoreactivity appeared in Muller cell somata and
      processes and its intensity increased between 1 day and 2 weeks post-lesion.
      Quantitative evaluation by immunoblotting confirmed that CNTF expression
      continuously increased up to 2 weeks after ischemic injury (to 600% of control
      levels), but had declined again to 250% of controls at 4 weeks post-lesion. Our
      findings suggest that CNTF supplied by Muller cells has a protective function for
      lesioned neurons following transient ischemia.

PMID- 10203347
TI  - Simultaneous monitoring of endothelin-1 and vasopressin plasma levels in
      migraine.
AB  - Vasopressin levels in plasma rise during migraine attacks. Vasopressin also
      induces endothelin-1 synthesis in endothelial cells, suggesting a role as a
      mediator of elevated plasma endothelin-1 in migraine. To explore a possible
      relationship between endothelin-1 and vasopressin in migraine, plasma
      concentrations of both peptides were monitored simultaneously throughout an
      attack and during two migraine-free intervals (control) in 20 patients.
      Endothelin-1 was elevated 6 h after the onset of an attack (3.3 +/- 0.3 pg/ml vs
      2.7 +/- 0.2 pg/ml during migraine-free intervals; p = 0.12) whereas vasopressin
      was increased over control levels (2.8 +/- 0.3 pg/ml) by 3 h (3.6 +/- 0.4 pg/ml;
      p < 0.05) and remained elevated at 6 h (3.9 +/- 0.5 pg/ml; p < 0.01). These data
      suggest that vasopressin may act as a peripheral mediator of increased plasma
      endothelin-1 in migraine.

PMID- 10203348
TI  - Low frequency of pathogenic mutations in the ubiquitin carboxy-terminal hydrolase
      gene in familial Parkinson's disease.
AB  - A coding substitution (I93M) in the ubiquitin carboxy-terminal L1 (UCH-L1) gene
      has recently been identified in a German family with Parkinson's disease. We have
      sequenced the entire coding region of the gene in 11 families who have a pattern
      of disease consistent with autosomal dominant inheritance. We found a
      polymorphism (S18Y) in exon 3, two polymorphisms in the 5' non-coding region,
      upstream of the transcription start, and an insertion/deletion polymorphism in
      intron 4. The S18Y allele is present on approximately 20% of chromosomes in a
      Caucasian population. These changes are, therefore, unlikely to be pathogenic. We
      conclude that the I93M variant must either be a rare cause of disease or a
      harmless substitution whose occurrence in the family reflects a chance co
      occurrence.

PMID- 10203349
TI  - Serotonin-containing cell bodies in novel brain locations: effects of light
      input.
AB  - Cell bodies staining positively for serotonin (5HT) appear in the suprachiasmatic
      nuclei (SCN) of hamsters that have been held in constant darkness (DD) for
      several months but are otherwise untreated. No such cell bodies are found in the
      SCN of animals that have been bilaterally enucleated for the same amount of time;
      however, in enucleated hamsters 5HT-containing cell bodies appear in the superior
      colliculus. These data provide the first indication that changes in sensory input
      can modulate 5HT levels in cells bodies outside of the raphe nuclei.

PMID- 10203350
TI  - Leptin immunoreactivity in the central nervous system in normal and diabetic
      rats.
AB  - An anti-leptin polyclonal antiserum was used to detect leptin-immunoreactivity (
      ir) in the central nervous system in rats. Leptin-ir was found in perikaryon and
      processes of neurons in the hypothalamus, including the paraventricular nucleus,
      and in several regions in the brainstem, including the nucleus of the solitary
      tract. In streptozotocin-treated diabetic rats, leptin-ir was dramatically
      attenuated only in the hypothalamus, and was restored by insulin treatment. Our
      findings that removal or restoration of systemic insulin regulates hypothalamic
      leptin-ir suggests that the leptin-ir observed in the brain is sensitive to
      peripheral hormone status. The presence of insulin-regulated leptin in the
      hypothalamus reveals a new avenue of research on the central actions of leptin in
      regulating energy balance and metabolism.

PMID- 10203351
TI  - Evidence for an essential role of megalin in transepithelial transport of
      retinol.
AB  - Transepithelial transport of retinol is linked to retinol-binding protein (RBP),
      which is taken up and also synthesized in a number of epithelia. By
      immunocytochemistry of human, rat, and mouse renal proximal tubules, a strong
      staining in apical endocytic vacuoles, lysosomes, endoplasmic reticulum, Golgi,
      and basal vesicles was observed, in accordance with luminal endocytic uptake as
      well as a constitutive synthesis and basal secretion of RBP. Analysis of mice
      with target disruption of the gene for the major endocytic receptor of proximal
      tubules, megalin, revealed no RBP in proximal tubules of these mice. Western
      blotting and HPLC of the urine of the megalin-deficient mice instead revealed a
      highly increased urinary excretion of RBP and retinol, demonstrating that
      glomerular filtered RBP-retinol of megalin-deficient mice escapes uptake by
      proximal tubules. A direct megalin-mediated uptake of purified RBP-retinol was
      indicated by surface plasmon resonance analysis and uptake in immortalized rat
      yolk sac cells. Uptake was partially inhibited by a polyclonal megalin antibody
      and the receptor-associated protein. The present data show that the absence of
      RBP-binding megalin causes a significantly increased loss of RBP and retinol in
      the urine, demonstrating a crucial role of megalin in vitamin A homeostasis.

PMID- 10203352
TI  - Regulation of aquaporin mRNA expression in rat kidney by water intake.
AB  - Three aquaporins (AQP) are present in the membrane of the principal collecting
      duct cells. On the apical side, the levels of AQP2 protein are increased in
      response to both arginine vasopressin and water deprivation. However, whether
      this change parallels changes in the abundance of AQP3 and AQP4 in the
      basolateral membrane is less well known. This study evaluates the effect of
      either dehydration or water loading on the rat kidney mRNA expression of AQP2,
      AQP3, and AQP4. Poly(A+)RNA was prepared from renal cortex and medulla of
      control, water-deprived, well hydrated, and water-deprived rats treated with
      OPC31260, a V2 receptor antagonist. Northern blots were done and mRNA levels were
      quantified using a PhosphorImager system. Relative to control, water deprivation
      increased the expression of cortical AQP2, -3, and -4, whereas water loading
      decreased the cortical and medullar expression of AQP2, -3, and -4. Therefore, in
      addition to AQP2 and -3, AQP4 expression is also regulated by water intake.
      Treatment with OPC31260 (40 mg/kg of weight per d) inhibited up to 20 to 30% the
      upregulation of AQP-mRNA induced by water deprivation. Blood values of arginine
      vasopressin and aldosterone were significantly increased by water deprivation,
      whereas they were unchanged by water overloading. Taken together, these results
      indicate that renal AQP2, -3, and -4 expression is regulated in a coordinated
      manner. Simultaneous up- or downregulation of the three transcripts occurred upon
      either water deprivation or water loading of animals, respectively. However, the
      signaling mechanism for the two long-term adaptive processes may be different,
      and, in addition to arginine vasopressin, other factors may be involved in the
      transcriptional regulatory processes.

PMID- 10203353
TI  - Downregulation of neuronal nitric oxide synthase in the rat remnant kidney.
AB  - Chronic renal failure is associated with disturbances in nitric oxide (NO)
      production. This study was conducted to determine the effect of 5/6 nephrectomy
      (5/6 Nx) on expression of intrarenal neuronal nitric oxide synthase (nNOS) in the
      rat. In normal rat kidney, nNOS protein was detected in the macula densa and in
      the cytoplasm and nuclei of cells of the inner medullary collecting duct by both
      immunofluorescence and electron microscopy. Western blot analysis revealed that 2
      wk after 5/6 Nx, there were significant decreases in nNOS protein expression in
      renal cortex (sham: 95.42+/-15.60 versus 5/6 Nx: 47.55+/-12.78 arbitrary units,
      P<0.05, n = 4) and inner medulla (sham: 147.70+/-26.96 versus 5/6 Nx: 36.95+/
      17.24 arbitrary units, P<0.005, n = 8). Losartan treatment was used to determine
      the role of angiotensin II (AngII) AT1 receptors in the inhibition of nNOS
      expression in 5/6 Nx. Losartan had no effect on the decreased expression of nNOS
      in the inner medulla, but partially increased nNOS protein expression in the
      cortex of 5/6 Nx rats. In contrast, in sham rats losartan significantly inhibited
      nNOS protein expression in the cortex (0.66+/-0.04-fold of sham values, P<0.05, n
      = 6) and inner medulla (0.74+/-0.12-fold of sham values, P<0.05, n = 6). nNOS
      mRNA was significantly decreased in cortex and inner medulla from 5/6 Nx rats,
      and the effects of losartan on nNOS mRNA paralleled those observed on nNOS
      protein expression. These data indicate that 5/6 Nx downregulates intrarenal nNOS
      mRNA and protein expression. In normal rats, AngII AT1 receptors exert a tonic
      stimulatory effect on expression of intrarenal nNOS. These findings suggest that
      the reduction in intrarenal nNOS expression in 5/6 Nx may play a role in
      contributing to hypertension and altered tubular transport responses in chronic
      renal failure.

PMID- 10203354
TI  - Natriuretic and diuretic actions of a highly selective adenosine A1 receptor
      antagonist.
AB  - The natriuretic and diuretic action of a highly selective adenosine A1 receptor
      (A1AdoR) antagonist, 1,3-dipropyl-8-[2-(5,6-epoxy)norbornyl]xanthine (CVT-124),
      was investigated in anesthetized rats. CVT-124 (0.1 to 1 mg/kg) caused dose
      dependent increases in urine flow and fractional and absolute sodium excretion of
      by six- to 10-fold and, at 0.1 mg/kg, increased the GFR (1.6+/-0.1 to 2.5+/-0.2
      ml/min; P<0.01). There were no changes in BP or heart rate. CVT-124 reduced
      absolute proximal reabsorption (26+/-3 to 20+/-2 nl/min; P<0.05) despite
      unchanged proximally measured, single-nephron GFR (SNGFR) (42+/-5 to 44+/-4
      nl/min; NS) and thereby decreased fractional proximal reabsorption (60+/-3 to
      46+/-4%; P<0.05). Despite increasing distal tubular fluid flow rate (5.4+/-0.7 to
      9.7+/-0.9 nl/min; P<0.001), it reduced the proximal-distal difference in SNGFR
      (before: 9.4+/-1.0 versus during CVT-124: 4.6+/-1.5 nl/min; P<0.01), suggesting
      that it had blunted the effects of the macula densa on SNGFR. Direct measurements
      of maximal tubuloglomerular feedback (TGF) responses were made from proximal stop
      flow pressure (PSF) during orthograde loop perfusion from the proximal tubule
      with artificial tubular fluid at 40 nl/min. TGF was blunted by intravenous CVT
      124 (0.5 mg/kg; deltaPSF with vehicle: 8.3+/-0.6 versus CVT-124: 6.5+/-0.3 mm Hg;
      n = 9; P<0.01). In conclusion, A1AdoR blockade reduces proximal reabsorption and
      uncouples it from glomerular filtration. It increases distal delivery of fluid
      yet does not activate a macula densa-dependent fall in SNGFR because it blunts
      the TGF response. Natriuresis accompanied by blockade of proximal
      glomerulotubular balance and TGF characterizes a new class of diuretic drugs.

PMID- 10203355
TI  - Inducible nitric oxide synthase can be induced in the absence of active nuclear
      factor-kappaB in rat mesangial cells: involvement of the Janus kinase 2 signaling
      pathway.
AB  - The contribution of nuclear factor-kappaB (NF-kappaB) and interferon-gamma (IFN
      gamma) signaling to nitric oxide generation is not completely understood. The
      effect of NF-kappaB release and its inhibition on nitrite production and the
      involvement of Janus kinase 2 (JAK2) in inducible nitric oxide synthase (iNOS)
      induction were investigated. The following assays were performed. (1) Nitrite
      produced by rat mesangial cells in primary culture was measured in incubations
      with tumor necrosis factor-alpha (TNF-alpha) or lipopolysaccharide (LPS), with or
      without IFN-gamma. Cells were stimulated with TNF-alpha or LPS plus IFN-gamma in
      the presence of NF-kappaB inhibitors, herbimycin A (HerA), or the more specific
      JAK2 inhibitor AG490. (2) Immunoblotting was performed against the p65 and p50
      subunits of NF-kappaB and iNOS. (3) Electrophoretic mobility shift assays were
      performed against NF-kappaB in the presence of NF-kappaB inhibitors or AG490. (4)
      iNOS promoter activity was measured in the presence of AG490 or JAK2 antisense
      oligonucleotides. TNF-alpha or LPS alone did not induce nitrite production, but
      with IFN-gamma these compounds did induce nitrite production. Pyrrolidine
      dithiocarbamate (PDTC), N-acetyl-L-cysteine, dexamethasone (Dex), HerA, and AG490
      partially inhibited LPS/ IFN-gamma- or TNF-alpha/IFN-gamma-induced nitrite
      production. p65 was inhibited by the three NF-kappaB inhibitors described above,
      whereas p50 was not. PDTC and Dex completely inhibited the p65/p50 heterodimer,
      but HerA and AG490 had little effect on p65/p50. AG490 and JAK2 antisense
      oligonucleotides suppressed iNOS promoter activity. It can be concluded that (1)
      iNOS can be induced without active NF-kappaB; (2) Dex, acetylsalicylic acid, and
      PDTC inhibit only p65; and (3) JAK2 is involved in iNOS induction, and the
      contribution of JAK2 to nitrite production is greater than that of NF-kappaB.

PMID- 10203356
TI  - Interaction of angiotensin II and mechanical stretch on vascular endothelial
      growth factor production by human mesangial cells.
AB  - The antiproteinuric effect of angiotensin-converting enzyme inhibitors
      underscores the importance of a hemodynamic injury and the renin-angiotensin
      system in the proteinuria of various glomerular diseases. Vascular endothelial
      growth factor (VEGF), a potent promoter of vascular permeability, is induced in
      mesangial cells by both mechanical stretch and TGF-beta1. This study investigates
      the effect of TGF-beta blockade, angiotensin II (AngII), and the interaction
      between AngII and stretch on human mesangial cell VEGF production. Exposure to
      AngII (1 microM) induced a significant increase in VEGF mRNA and protein levels
      (1.5+/-0.1 and 1.7+/-0.3, respectively, fold increase over control, P<0.05). The
      AngII receptor (AT1) antagonist Losartan (10 microM) prevented AngII-induced, but
      not stretch-induced, VEGF protein secretion (AngII 1.7+/-0.3, AngII + Losartan
      1.0+/-0.1, P<0.05; stretch 2.4+/-0.4, stretch + Losartan 2.6+/-0.5). Stretch
      induced VEGF production was also unaffected by the addition of an anti-TGF-beta
      neutralizing antibody (stretch 2.85+/-0.82 versus stretch + anti-TGF-beta 2.84+/
      0.01, fold increase over control). Simultaneous exposure to both AngII and
      stretch for 12 h had an additive effect on VEGF production (AngII 1.6+/-0.1,
      stretch 2.6+/-0.27, AngII + stretch 3.1+/-0.35). Conversely, preexposure to
      stretch magnified AngII-induced VEGF protein secretion (unstretched + AngII 1.3+/
      0.0, stretched + AngII 1.9+/-0.1, P<0.01) with a parallel 1.5-fold increase in
      AT1 receptor levels. AngII and stretch can both independently induce VEGF
      production; in addition, mechanical stretch upregulates the AT1 receptor,
      enhancing the cellular response to AngII.

PMID- 10203357
TI  - Mechanisms of mitogen-activated protein kinase activation in experimental
      diabetes.
AB  - Various growth factors and vasoactive substances are implicated in the
      pathogenesis of renal growth seen in early diabetes mellitus (DM). Mitogen
      activated protein kinase (MAPK) is an important mediator of these extracellular
      stimuli. Protein kinase C (PKC), an enzyme known to be stimulated in DM, also
      activates MAPK. Thus, MAPK activity was examined in glomeruli from streptozotocin
      induced DM rats. MAPK activity, measured as myelin basic protein kinase, was
      elevated by approximately 50% in DM versus controls (CON). Increased protein
      contents of p42mapk and p44mapk, as well as increased tyrosine phosphorylation
      and mobility shift of p42mapk, were also observed in DM. Tyrosine
      dephosphorylation of pp42mapk, on the other hand, assessed by incubating
      glomerular membrane with or without sodium orthovanadate (vanadate), was
      significantly diminished in DM. Protein expression of MAPK phosphatase-1 (MKP-1),
      a dual specificity phosphatase that inactivates MAPK, was approximately 60% of
      CON. Reduction in MKP-1 was reproduced in cultured mesangial cells grown under
      high glucose (30 mM; HG). The suppression of MKP-1 was PKC-dependent since
      incubation of HG cells with phorbol 12-myristate 13-acetate for 24 h abolished
      it. Furthermore, calcium ionophore A23187 reversed the suppression, suggesting
      that blunted Ca2+ signalling, characteristic of HG cells secondary to PKC
      stimulation, may be the cause. These results demonstrate that glomerular MAPK is
      activated in DM by multiple mechanisms i.e., increases in protein contents,
      increased phosphorylation, and decreased dephosphorylation of the enzyme due to
      suppression of MKP-1. These alterations may have an implication in the
      pathogenesis of diabetic nephropathy.

PMID- 10203358
TI  - The antioxidant N-acetylcysteine induces mesangial cells to create three
      dimensional cytoarchitecture that underlies cellular differentiation.
AB  - Prolonged culture of mesangial cells produces multifocal nodular structures,
      i.e., "hillocks," consisting of cells and extracellular matrix. Hillock formation
      is associated with induction of a differentiated phenotype of mesangial cells,
      with suppressed mitogenesis and downregulation of alpha-smooth muscle actin
      (alpha-SMA). Currently, little is understood regarding physiologically relevant
      factors that facilitate this cytodifferentiation. This study explores whether and
      how the cellular redox state modulates hillock formation. Exposure of confluent
      rat mesangial cells to the antioxidant N-acetylcysteine (NAC), an inducer of
      glutathione, dramatically facilitated hillock formation. This effect was mimicked
      by external addition of the reduced form of glutathione ethyl ester. In contrast,
      the oxidizing agents diamide and menadione inhibited the development of hillocks
      triggered by either NAC, glutathione, or prolonged culture. The induction of
      hillocks by NAC was correlated with downregulation of alpha-SMA as well as
      attenuated activity of the CArG box element (the cis-element relevant to the
      expression of the alpha-SMA gene and growth-associated genes). These results
      indicate that, by a redox-sensitive mechanism, NAC induces mesangial cells to
      create three-dimensional cytoarchitecture that underlies cellular
      differentiation.

PMID- 10203359
TI  - IFN-gamma mediates crescent formation and cell-mediated immune injury in murine
      glomerulonephritis.
AB  - Features of crescentic glomerulonephritis suggest that it results from a T helper
      1 (Th1) nephritogenic immune response. Interferon-gamma (IFN-gamma), produced by
      Th1 cells, is involved in T cell-directed macrophage activation in effector Th1
      responses. The hypothesis that endogenous IFN-gamma contributes to the
      development of crescentic glomerulonephritis was tested by comparing the
      development of glomerulonephritis (induced by a planted antigen) and immune
      responses in normal C57BL/6 mice (IFN-gamma +/+) and in mice genetically
      deficient in IFN-gamma (IFN-gamma -/-). Ten days after the initiation of
      glomerulonephritis, IFN-gamma -/- mice developed fewer glomerular crescents (5+/
      1% versus 26+/-3%, P<0.005), less severe glomerular injury, and less renal
      impairment. Effectors of delayed-type hypersensitivity (CD4+ T cells,
      macrophages, and fibrin) in glomeruli were reduced in IFN-gamma -/- mice. Skin
      delayed-type hypersensitivity to sheep globulin was reduced. Total antigen
      specific Ig and splenocyte interleukin-2 production were unchanged, but antigen
      specific serum IgG2a was reduced. Markers of an antigen-specific Th2 response
      (serum IgG1, splenocyte interleukin-4) were unchanged. Studies 22 d after the
      initiation of glomerulonephritis showed that IFN-gamma -/- mice still had fewer
      crescents (11+/-2% versus 22+/-3%, P = 0.02) and glomerular CD4+ T cells and
      macrophages than IFN-gamma +/+ mice. These studies demonstrate that endogenous
      IFN-gamma mediates crescentic glomerulonephritis by promoting cell-mediated
      immune injury. They support the hypothesis that crescentic glomerulonephritis is
      a manifestation of a Th1 nephritogenic immune response.

PMID- 10203360
TI  - Underglycosylation of IgA1 hinge plays a certain role for its glomerular
      deposition in IgA nephropathy.
AB  - This study was performed to isolate and investigate the IgA1 that could
      accumulate in glomeruli (glomerulophilic IgA1). IgA1 was fractionated by the
      electric charge and the reactivity to Jacalin. Serum IgA1 of IgA nephropathy
      patients was separated and fractionated using a Jacalin column and subsequent ion
      exchange chromatography. The fractions were divided into three groups of
      relatively cationic (C), neutral (N), and anionic (A). IgA1 was also divided into
      Jacalin low (L), intermediate (I), and high (H) affinity fractions by serial
      elution using 25, 100, and 800 mM galactose. The left kidneys of Wistar rats were
      perfused with 2, 5, or 10 mg of each group of IgA1. The rats were sacrificed 15
      min, 30 min, 3 h, or 24 h after the perfusion. The accumulation of each IgA1 in
      the glomeruli was then observed by immunofluorescence. The IgA1 of the fractions
      N and H separated by the two methods was definitely accumulated in the rat
      glomeruli with a similar pattern. The electrophoresis revealed that the
      macromolecular IgA1 was increased in fraction H compared with other fractions.
      Therefore, Jacalin high-affinity IgA1(fraction H) was applied on a
      diethylaminoethyl column and divided into electrically cationic (HC), neutral
      (HN), and anionic (HA). Only the asialo-Galbeta1,3GalNAc chain was identified in
      the fraction HN IgA1 by gas-phase hydrazinolysis. Furthermore, the IgA1 fraction
      was strongly recognized by peanut agglutinin, Vicia Villosa lectins, and
      antisynthetic hinge peptide antibody. These results indicated that the IgA1
      molecules having the underglycosylated hinge glycopeptide played a certain role
      in the glomerular accumulation of IgA1 in IgA nephropathy.

PMID- 10203361
TI  - Human mesangial cells in culture and in kidney sections fail to express Fc alpha
      receptor (CD89).
AB  - The mechanism of deposition of IgA in the renal mesangium in primary IgA
      nephropathy is poorly understood. It has been suggested that membrane receptors
      for IgA on mesangial cells (MC) of the kidney may be involved. To obtain more
      insight in the occurrence of the myeloid receptor for IgA (CD89) on MC, both in
      situ and in culture, rabbit and goat polyclonal antibodies and mouse monoclonal
      antibody against recombinant CD89 were raised. Kidney sections from five control
      subjects and five patients with primary IgA-nephropathy failed to be positive for
      CD89 in the mesangium, using our polyclonal and monoclonal antibodies. Also, five
      primary human MC cultures assessed for CD89 expression showed no protein
      expression of CD89. Furthermore, reverse transcription-PCR failed to detect mRNA
      expression of CD89 in the cultured MC. It was demonstrated that all five human
      primary MC bound human IgA in a dose-dependent manner, which was not inhibitable
      by blocking monoclonal anti-CD89 antibody (My43). In contrast, binding of IgA to
      U937 cells was blocked efficiently by My43. Finally, incubation of human MC with
      either human or rat IgA led to increased interleukin-6 production, whereas only
      human IgA, but not rat IgA, was able to bind to human CD89. Therefore, it is
      concluded that human MC do not express CD89 (to a significant extent). These
      results strongly suggest that binding of IgA to human MC occurs via an IgA
      receptor distinct from CD89.

PMID- 10203362
TI  - Alpha1beta1 integrin-mediated collagen matrix remodeling by rat mesangial cells
      is differentially regulated by transforming growth factor-beta and platelet
      derived growth factor-BB.
AB  - Pathologic remodeling of mesangial matrix after glomerular injury is the central
      biologic feature of glomerular scarring (sclerosis). Transforming growth factor
      beta (TGF-beta) and platelet-derived growth factor (PDGF)-BB have been implicated
      in the development of glomerular scarring in rat and human glomerulonephritis. To
      clarify molecular and cellular mechanisms involved in abnormal mesangial
      remodeling, this study focused on the role of alpha1beta1 integrin, a
      collagen/laminin receptor, in rat mesangial cells, using collagen gel contraction
      as an experimental model of in vivo collagen matrix remodeling and scar
      formation. In addition, the influence of TGF-beta and PDGF-BB on mesangial cell
      (MC)-mediated collagen gel contraction in association with the alpha1beta1
      integrin expression was evaluated. Integrin function blocking studies using anti
      alpha1, beta1 subunit antibodies indicated that MC-alpha1beta1 integrin is
      essentially required not only for collagen-dependent adhesion/migration, but also
      for gel contraction. Protein synthesis and mRNA analysis experiments demonstrated
      that TGF-beta, but not PDGF-BB, increases the expression of alpha1beta1 integrin
      in mesangial cells cultured on plastic surface and in collagen gels. The
      upregulation of alpha1beta1 integrin expression by TGF-beta correlated with
      increases in gel contraction and collagen-dependent adhesion but not migration of
      mesangial cells. On the other hand, PDGF-BB enhanced MC-mediated gel contraction
      and migration without affecting cell adhesion to collagen I. Growth factor
      induced collagen-dependent adhesion, migration, and gel contraction were
      significantly attenuated by incubation with anti-alpha1, beta1 subunit
      antibodies. Thus, these data indicate that alpha1beta1 integrin-mediated collagen
      matrix remodeling can be modulated by TGF-beta and PDGF-BB via different
      mechanisms. Alpha1 integrin-mediated mesangial matrix remodeling induced by TGF
      beta or PDGF-BB may be a pathogenic mechanism leading to glomerular scarring.

PMID- 10203363
TI  - Transforming growth factor-beta is a potent inhibitor of extracellular matrix
      degradation by cultured human mesangial cells.
AB  - Accumulation of the glomerular extracellular matrix (ECM) is a pivotal event in
      the progression from acute glomerular injury to end-stage renal disease. Although
      enhanced ECM synthesis has been demonstrated to contribute to ECM accumulation,
      the role of decreased ECM degradation is largely unknown. It was previously shown
      that glomerular ECM degradation is mediated by a plasminogen activator
      (PA)/plasmin/matrix metalloproteinase 2 (MMP-2) cascade. However, little
      information is available regarding the factors that regulate the activity of this
      degradative cascade in normal or pathologic states. Transforming growth factor
      beta1 (TGF-beta1) is shown here to be a potent inhibitor of ECM degradation by
      cultured human mesangial cells. Using human mesangial cells grown on thin films
      of 125I-labeled Matrigel, dose-dependent inhibition of ECM degradation in the
      presence of TGF-beta1 was observed, reaching >90% inhibition with 0.4 ng/ml TGF
      beta1. Addition of anti-TGF-beta antibodies (4 microg/ml) in the absence of
      exogenous TGF-beta increased ECM degradation (1.8+/-0.2-fold versus controls,
      P<0.05). In contrast, platelet-derived growth factor, at concentrations up to 10
      ng/ml, had no effect on ECM degradation. TGF-beta completely blocked the
      conversion of plasminogen to plasmin and markedly reduced the conversion of
      latent MMP-2 to active MMP-2. TGF-beta did not significantly alter the levels of
      tissue PA, total MMP-2, or tissue inhibitor of metalloproteinase-1, but did
      increase the levels of PA inhibitor- (1.8-fold, P<0.05), the major physiologic
      inhibitor of PA. These data document that TGF-beta is a potent inhibitor of ECM
      degradation by cultured human mesangial cells, and they suggest that decreased
      mesangial matrix degradation, caused by TGF-beta-mediated decreases in the
      activity of the PA/plasmin/MMP-2 cascade, may contribute to the glomerular matrix
      accumulation that occurs in progressive renal disease.

PMID- 10203365
TI  - Antiproteinuric therapy while preventing the abnormal protein traffic in proximal
      tubule abrogates protein- and complement-dependent interstitial inflammation in
      experimental renal disease.
AB  - In proteinuric glomerulopathies, the excess traffic of proteins into the renal
      tubule is a candidate trigger of interstitial inflammatory and immune events
      leading to progressive injury, and a key target for the renoprotective action of
      antiproteinuric drugs. Among proteins trafficked to the proximal tubule, the
      third component of complement (C3) can be activated locally and contribute to
      inflammation at sites of protein reabsorption. Experiments were performed in rats
      with renal mass reduction (RMR, 5/6 nephrectomy) with the following aims: (1) to
      study Ig (IgG) and complement deposition in proximal tubules, and interstitial
      macrophage infiltration and MHC class II expression at intervals after surgery by
      double immunofluorescence analysis; (2) to assess whether lisinopril (angiotensin
      converting enzyme inhibitor [ACEi], 25 mg/L in the drinking water, from either
      day 1 or day 7) limited IgG and C3 accumulation and interstitial inflammation at
      day 30. In 7-d remnant kidneys, intracellular staining for both IgG and C3 was
      detectable in proximal tubules in focal areas; C3 was restricted to IgG-positive
      tubular cells, and there were no interstitial ED-1 macrophage and MHC II-positive
      cellular infiltrates. In 14-d and 30-d remnant kidneys, proximal tubular IgG and
      C3 staining was associated with the appearance of interstitial infiltrates that
      preferentially localized to areas of tubules positive for both proteins. RMR rats
      given ACEi had no or limited increases in levels of urinary protein excretion,
      tubular IgG, and C3 reactivity, and interstitial cellular infiltrates in kidneys
      at 30 d, even when ACEi was started from day 7 after surgery. These findings
      document that (1) in RMR, IgG and C3 accumulation in proximal tubular cells is
      followed by leukocyte infiltration and MHC II overexpression in the adjacent
      interstitium; (2) ACEi while preventing proteinuria limits both tubular
      accumulation of IgG and C3 and interstitial inflammation. The data suggest that
      ACE inhibition can be renoprotective by limiting the early abnormal protein
      traffic in proximal tubule and consequent deleterious effects of excess protein
      reabsorption, including the accumulation and local activation of complement as
      well as the induction of chemokines and endothelin genes known to promote
      interstitial inflammation and fibrosis.

PMID- 10203364
TI  - Parathyroid hormone-related protein (107-139) stimulates interleukin-6 expression
      in human osteoblastic cells.
AB  - The N-terminal region of both parathyroid hormone (PTH) and PTH-related protein
      (PTHrP) binds to the same PTH/PTHrP receptor in osteoblasts. However, C-terminal
      PTHrP (107-139) inhibits growth and various functions of osteoblasts and
      osteoclasts apparently through PTHrP-specific receptors. PTH (1-34) and PTHrP (1
      34) rapidly induce interleukin-6 (IL-6) expression by osteoblasts. The aim of the
      present study was to assess the effects of PTHrP (107-139) on IL-6 gene
      expression and secretion by osteoblastic cells from human trabecular bone (hOB).
      Using reverse transcription followed by PCR, it was found that IL-6 mRNA was
      twofold maximally increased by either PTHrP (1-34) or PTHrP (107-139), at 10 nM,
      over basal within 1 to 2 h in hOB cells. This effect of PTHrP (107-139), and that
      of PTHrP (1-34), were abolished by the transcription inhibitor actinomycin D.
      Meanwhile, puromycin, a protein synthesis inhibitor, superinduced IL-6 expression
      in the presence or absence of each PTHrP peptide. Both PTHrP (1-34) and PTHrP
      (107-139), but not PTHrP (38-64), stimulated IL-6 secretion to the hOB cell
      conditioned medium at 24 h, dose dependently. In addition, this maximal
      stimulatory effect (twofold over basal) was similar with each PTHrP peptide
      alone, and not additive when added together. PTHrP (107-139) stimulation of mRNA
      and protein in hOB cells was abolished by bisindolylmaleimide I, a protein kinase
      C inhibitor, but not by either adenosine 3',5'-cyclic monophosphorothioate, Rp
      isomer (Rp-cAMPS), or N-[2-((p-bromocinnamyl)amino)ethyl]-5
      isoquinolinesulfonamide dihydrochloride (H89), two protein kinase A inhibitors.
      These results indicate that C-terminal PTHrP, like its N-terminal domain, induces
      IL-6 production by human osteoblastic cells. This effect of both PTHrP regions
      could provide a mechanism to modulate bone turnover.

PMID- 10203366
TI  - Resistance to remnant nephropathy in the Wistar-Furth rat.
AB  - The Wistar-Furth rat, an inbred strain resistant to actions of
      mineralocorticoids, was used to study the concept that mineralocorticoids
      contribute to progressive renal injury. It was postulated that if chronic
      nephropathy depends on aldosterone and if Wistar-Furth rats are resistant to
      aldosterone, remnant nephropathy would be attenuated in Wistar-Furth rats. Wistar
      Furth rats and control Wistar rats were subjected to 5/6 nephrectomy or a sham
      procedure and then followed for 4 wk. Renal ablation resulted in hypertension at
      4 wk in both strains (164+/-5 [Wistar-Furth] versus 184+/-7 [Wistar] mm Hg mean
      arterial pressure), with sham animals remaining normotensive (134+/-6 mm Hg).
      Renal damage in response to 5/6 nephrectomy was greatly decreased in Wistar-Furth
      rats compared with Wistar rats. Albuminuria was markedly less in Wistar-Furth
      rats (12.7+/-4.2 [Wistar-Furth] versus 97.4+/-22.6 [Wistar] mg/d per 100 g body
      wt, P<0.01). Glomerular damage, consisting of mesangial proliferation, mesangial
      lysis, and segmental necrosis, was observed in 42% of glomeruli from Wistar rats
      but in 0% of glomeruli from Wistar-Furth rats (P<0.01). To address the
      possibility that higher BP in partially nephrectomized Wistar rats mediated the
      greater renal damage, the study was repeated, with Wistar rats (not Wistar-Furth
      rats) being treated with a hydralazine-reserpine-hydrochlorothiazide regimen.
      Although this antihypertensive regimen equalized BP (conscious systolic) (144+/-8
      mm Hg [Wistar] versus 157+/-7 mm Hg [Wistar-Furth] at 4 wk), albuminuria remained
      more than 10-fold greater in Wistar rats. In summary, renal damage upon 5/6
      nephrectomy was markedly reduced in Wistar-Furth rats, a finding not attributable
      to reduced systemic BP. Since Wistar-Furth rats have been shown previously to be
      resistant to the actions of mineralocorticoids, the data from the present study
      support the hypothesis that aldosterone mediates, at least in part, the renal
      injury attendant to renal mass reduction.

PMID- 10203367
TI  - Immunohistochemical evidence for an increased oxidative stress and carbonyl
      modification of proteins in diabetic glomerular lesions.
AB  - Advanced glycation end products (AGE) include a variety of protein adducts whose
      accumulation has been implicated in tissue damage associated with diabetic
      nephropathy (DN). It was recently demonstrated that among AGE, glycoxidation
      products, whose formation is closely linked to oxidation, such as
      carboxymethyllysine (CML) and pentosidine, accumulate in expanded mesangial
      matrix and nodular lesions in DN, in colocalization with malondialdehyde-lysine
      (MDA-lysine), a lipoxidation product, whereas pyrraline, another AGE structure
      whose deposition is rather independent from oxidative stress, was not found
      within diabetic glomeruli. Because CML, pentosidine, and MDA-lysine are all
      formed under oxidative stress by carbonyl amine chemistry between protein amino
      group and carbonyl compounds, their colocalization suggests a local oxidative
      stress and increased protein carbonyl modification in diabetic glomerular
      lesions. To address this hypothesis, human renal tissues from patients with DN or
      IgA nephropathy were examined with specific antibodies to characterize most, if
      not all, carbonyl modifications of proteins by autoxidation products of
      carbohydrates, lipids, and amino acids: CML (derived from carbohydrates, lipids,
      and amino acid), pentosidine (derived from carbohydrates), MDA-lysine (derived
      from lipids), 4-hydroxynonenal-protein adduct (derived from lipids), and acrolein
      protein adduct (derived from lipids and amino acid). All of the protein adducts
      were identified in expanded mesangial matrix and nodular lesions in DN. In IgA
      nephropathy, another primary glomerular disease leading to end-stage renal
      failure, despite positive staining for MDA-lysine and 4-hydroxynonenal-protein
      adduct in the expanded mesangial area, CML, pentosidine, and acrolein-protein
      adduct immunoreactivities were only faint in glomeruli. These data suggest a
      broad derangement in nonenzymatic biochemistry in diabetic glomerular lesions,
      and implicate an increased local oxidative stress and carbonyl modification of
      proteins in diabetic glomerular tissue damage ("carbonyl stress").

PMID- 10203368
TI  - Mycophenolate mofetil therapy in lupus nephritis: clinical observations.
AB  - Controlled clinical trials in renal transplantation have demonstrated that
      mycophenolate mofetil is well tolerated and has lower renal transplant rejection
      rates than azathioprine regimens. This study reports on the clinical experiences
      at two institutions with mycophenolate mofetil (MMF) for severe lupus nephritis.
      Twelve patients with relapsing or resistant nephritis previously treated with
      cyclophosphamide therapy and one patient who refused cyclophosphamide as initial
      therapy for diffuse proliferative nephritis but accepted MMF were included.
      During combined MMF/prednisone therapy, serum creatinine values remained normal
      or declined from elevated values: mean change in serum creatinine was -0.26+/
      0.46 microM/L, P = 0.039. Proteinuria significantly decreased: mean change in
      urine protein-to-creatinine ratios was -2.53+/-3.76, P = 0.039. Decreased serum
      complement component C3 and elevated anti-double-stranded DNA antibody levels at
      baseline improved in some, but not all, patients. The mean initial dose of MMF
      was 0.92 g/d (range, 0.5 to 2 g/d). The mean duration of therapy was 12.9 mo
      (range, 3 to 24 mo). Adverse events included herpes simplex stomatitis associated
      with severe leukopenia (n = 1), asymptomatic leukopenia (n = 2), nausea/ diarrhea
      (n = 2), thinning of scalp hair (n = 1), pancreatitis (n = 1), and pneumonia
      without leukopenia (n = 1). Recurrence of the pancreatitis led to discontinuation
      of MMF in this patient; all other adverse events resolved with dose reduction. It
      is concluded that MMF is well tolerated and has possible efficacy in controlling
      major renal manifestations of systemic lupus erythematosus. Controlled clinical
      trials are needed to define the role of MMF in the management of lupus nephritis.

PMID- 10203369
TI  - Intake of vitamins B6 and C and the risk of kidney stones in women.
AB  - Urinary oxalate is an important determinant of calcium oxalate kidney stone
      formation. High doses of vitamin B6 may decrease oxalate production, whereas
      vitamin C can be metabolized to oxalate. This study was conducted to examine the
      association between the intakes of vitamins B6 and C and risk of kidney stone
      formation in women. The relation between the intake of vitamins B6 and C and the
      risk of symptomatic kidney stones were prospectively studied in a cohort of
      85,557 women with no history of kidney stones. Semiquantitative food-frequency
      questionnaires were used to assess vitamin consumption from both foods and
      supplements. A total of 1078 incident cases of kidney stones was documented
      during the 14-yr follow-up period. A high intake of vitamin B6 was inversely
      associated with risk of stone formation. After adjusting for other dietary
      factors, the relative risk of incident stone formation for women in the highest
      category of B6 intake (> or =40 mg/d) compared with the lowest category (<3 mg/d)
      was 0.66 (95% confidence interval, 0.44 to 0.98). In contrast, vitamin C intake
      was not associated with risk. The multivariate relative risk for women in the
      highest category of vitamin C intake (> or =1500 mg/d) compared with the lowest
      category (<250 mg/d) was 1.06 (95% confidence interval, 0.69 to 1.64). Large
      doses of vitamin B6 may reduce the risk of kidney stone formation in women.
      Routine restriction of vitamin C to prevent stone formation appears unwarranted.

PMID- 10203371
TI  - Effect of normalization of hematocrit on brain circulation and metabolism in
      hemodialysis patients.
AB  - Full correction of anemia with recombinant human erythropoietin (rhEPO) has been
      reported to reduce the risk of cardiovascular morbidity and mortality and improve
      the quality of life in hemodialysis (HD) patients. Effects of normalization of
      hematocrit on cerebral blood flow and oxygen metabolism were investigated by
      positron emission tomography. Regional cerebral blood flow (rCBF), cerebral blood
      volume (rCBV), oxygen extraction ratio (rOER), and metabolic rate for oxygen
      (rCMRO2) were measured in seven HD patients before and after correction of anemia
      and compared with those in six healthy control subjects. In addition, blood
      rheology before and on rhEPO therapy was measured in HD patients, which included
      blood viscosity, plasma viscosity, erythrocyte fluidity, and erythrocyte
      aggregability. The results showed that plasma viscosity was high (1.51+/-0.19 mPa
      x s) and erythrocyte fluidity was low (85.8+/-4.8 Pa(-1) x s(-1)), while whole
      blood viscosity was within the normal range (3.72+/-0.38 mPa x s) before rhEPO
      therapy. After treatment, the hematocrit rose significantly from 29.3+/-3.3 to
      42.4+/-2.2% (P<0.001), accompanied by a significant increase in the whole blood
      viscosity to 4.57+/-0.16 mPa x s, nonsignificant decrease in erythrocyte fluidity
      to 79.9+/-7.4 mPa(-1) x s(-1) and nonsignificant change in plasma viscosity
      (1.46+/-1.3 mPa x s). Positron emission tomography measurements revealed that by
      normalization of hematocrit, rCBF significantly decreased from 65+/-11 to 48+/-12
      ml/min per 100 cm3 (P<0.05). However, arterial oxygen content (caO2)
      significantly increased from 5.7+/-0.7 to 8.0+/-0.4 mmol/L (P<0.0001), rOER of
      the hemispheres significantly increased from 44+/-3 to 51+/-6% (P<0.05) and
      became significantly higher than healthy control subjects (P<0.05). In addition,
      rCBV significantly increased from 3.5+/-0.5 to 4.6+/-0.6 ml/100 cc brain tissue.
      The results showed that oxygen supply to the brain tissue increased with
      normalization of hematocrit, but it was accompanied by increased oxygen
      extraction in the brain tissue. This may be assumed to be related to the decrease
      of erythrocyte velocity in the cerebral capillaries as a result of the decreased
      blood deformability and the increased plasma viscosity.

PMID- 10203370
TI  - Cytokine removal during continuous hemofiltration in septic patients.
AB  - A potential application of the continuous renal replacement therapies is the
      extracorporeal removal of inflammatory mediators in septic patients. Cytokine
      elimination with continuous renal replacement therapies has been demonstrated in
      several clinical studies, but so far without important effects on their serum
      concentrations. Improved knowledge of the cytokine removal mechanisms could lead
      to the development of more efficient treatment strategies. In the present study,
      15 patients with septic shock and acute renal failure were observed during the
      first 24 h of treatment with continuous venovenous hemofiltration (CVVH) with an
      AN69 membrane. After 12 h, the hemofilter was replaced and the blood flow rate
      (QB) was switched from 100 ml/min to 200 ml/min or vice versa. Pre- and
      postfilter plasma and ultrafiltrate concentrations of selected inflammatory and
      anti-inflammatory cytokines were measured at several time points allowing the
      calculation of a mass balance. Cytokine removal was highest 1 h after the start
      of CVVH and after the change of the membrane (ranging from 25 to 43% of the
      prefilter amount), corresponding with a significant fall in the serum
      concentration of all cytokines. The inhibitors of inflammation were removed to
      the same extent as the inflammatory cytokines. Adsorption to the AN69 membrane
      appeared to be the main clearance mechanism, being most pronounced immediately
      after installation of a new membrane and decreasing steadily thereafter,
      indicating rapid saturation of the membrane. A QB of 200 ml/min was associated
      with a 75% increase of the ultrafiltration rate and a significantly higher
      convective elimination and membrane adsorption than at a QB of 100 ml/min. The
      results indicate that optimal cytokine removal with CVVH with an AN69 membrane
      could be achieved with a combination of a high QB/ultrafiltration rate and
      frequent membrane changes.

PMID- 10203372
TI  - Serum levels and metabolic clearance of the isoflavones genistein and daidzein in
      hemodialysis patients.
AB  - Genistein and daidzein are biologically active isoflavones that are especially
      abundant in soybeans. After intestinal absorption, circulating genistein and
      daidzein are eliminated primarily by the kidneys. This study was undertaken to
      assess the metabolism of genistein and daidzein in patients with end-stage renal
      disease (ESRD) on hemodialysis therapy, and to test whether this treatment
      modality can replace the lack of kidney function, with respect to the elimination
      of the isoflavones. Twenty-three hemodialysis patients and 10 healthy subjects
      were studied. While consuming a self-selected low isoflavone diet, baseline blood
      levels were undetectable in eight of 10 healthy subjects and in 14 of 23 dialysis
      patients. The remaining participants had detectable levels, with the nine
      dialysis patients displaying much higher blood concentrations than the two
      healthy control subjects. After the evening intake of one dose of an isoflavone
      rich soy protein isolate drink, the early morning blood levels of genistein and
      daidzein were higher in seven dialysis patients than in eight healthy subjects
      (genistein 1271+/-321 versus 425+/-104, P<0.05; daidzein 1304+/-352 versus 292+/
      78, P<0.05). The blood clearance of the isoflavones was studied in two healthy
      subjects and in three dialysis patients. Genistein and daidzein were eliminated
      within 2 d in the healthy subjects, but had not returned to baseline in two of
      three ESRD patients, 7 d after intake. The half-life of both compounds was
      estimated to be 10-fold longer in the ESRD patients than in the healthy subjects.
      Finally, genistein and daidzein levels were measured before and after dialysis in
      five patients, both while on their regular diet and after one dose of a soy
      protein isolate drink. In both instances, the dialysis treatment did not affect
      the blood isoflavone levels. In conclusion, approximately one-third of
      hemodialysis patients eating the standard American renal diet experience high
      blood levels of the isoflavones genistein and daidzein, while the remaining two
      thirds have undetectable levels. After ingestion of isoflavone-rich food such as
      soy products, all patients have detectable levels that remain very high for
      several days due to lack of renal excretion.

PMID- 10203373
TI  - Clinical practice guidelines in end-stage renal disease: a strategy for
      implementation.
AB  - Clinical practice guidelines (CPGs) for end-stage renal failure (ESRD) were
      recently published, and represent a comprehensive review of available literature
      and the considered judgment of experts in ESRD. To prioritize and implement these
      guidelines, the evidence underlying each guideline should be ranked and the
      attributes of each should be defined. Strategies to improve practice patterns
      should be tested. Focused information for each high priority guideline should be
      disseminated, including a synopsis and assessment of the underlying evidence, the
      evidence model used to develop that guideline, and suggested strategies for CPG
      implementation. Clinical performance measures should be developed and used to
      measure current practice, and the success of changing practice patterns on
      clinical outcomes. Individual practitioners and dialysis facilities should be
      encouraged to utilize continuous quality improvement techniques to put the
      guidelines into effect. Local implementation should proceed at the same time as a
      national project to convert high priority CPGs into clinical performance measures
      proceeds. Patients and patient care organizations should participate in this
      process, and professional organizations must make a strong commitment to educate
      clinicians in the methodology of CPG and performance measure development and the
      techniques of continuous quality improvement. Health care regulators should
      understand that CPGs are not standards, but are statements that assist
      practitioners and patients in making decisions.

PMID- 10203374
TI  - Phosphorus, regulation of plasma calcium, and secondary hyperparathyroidism: a
      hypothesis to integrate a historical and modern perspective.

PMID- 10203375
TI  - Hyperhomocysteinemia in chronic renal disease.

PMID- 10203376
TI  - Continuous ambulatory peritoneal dialysis. 1978.

PMID- 10203377
TI  - Thymus volume correlates with the progression of vertical HIV infection.
AB  - BACKGROUND: The thymus is the organ responsible for the maturation and selection
      of T lymphocytes and is thus pivotal in allowing the development of a functional
      immune system. Because in HIV infection cell-mediated immune responses are
      severely impaired, we studied the role of thymus in the control of the
      progression of HIV infection to AIDS. METHODS: Thymic volume was analysed by
      magnetic resonance imaging in 31 vertically HIV-infected children. Plasma HIV
      viral load and phenotypic and functional cellular immunity-defining parameters
      were examined in the same patients. RESULTS: Thymic volume was not correlated
      with age or nutritional status; thymic volume was nevertheless correlated with
      CD4 T-lymphocyte counts and with the percentage and absolute number of
      CD45RA+CD62L+ (naive) T lymphocytes. In addition, the ability of peripheral blood
      mononuclear cells to proliferate upon tetanus stimulation was directly
      proportional to thymic volume. Finally, a negative correlation was detected
      between thymic volume and HIV viral load. CONCLUSION: Because low HIV plasma
      viraemia and preserved immune function are favourable prognostic indices in HIV
      disease, these data indicate that an immunological, thymic-dependent control of
      the progression of HIV infection might be possible, at least in vertically
      transmitted HIV infection.

PMID- 10203379
TI  - Chemokine and chemokine receptor expression after combined anti-HIV-1 interleukin
      2 therapy.
AB  - OBJECTIVE: To evaluate changes in serum levels of chemokines, chemokine
      production, and chemokine receptor expression by peripheral blood mononuclear
      cells (PBMC), after treatment of HIV-1-infected individuals with interleukin (IL)
      2. METHODS: We determined CC-chemokine levels by enzyme-linked immunosorbent
      assay and chemokine receptor expression using FACS analysis or reverse
      transcriptase polymerase chain reaction in samples from patients receiving highly
      active antiretroviral therapy (HAART) supplemented with low doses of recombinant
      IL-2. Results were compared with a control group of patients receiving HAART.
      RESULTS: Serum levels of RANTES, macrophage inflammatory protein (MIP)-1alpha and
      MIP-1beta, and the production of these chemokines by unstimulated and stimulated
      PBMC, were not modified by IL-2 administration. In contrast, the IL-2-treated
      group showed increased expression of CXC-chemokine receptor (CXCR)-4 in the CD4 T
      cell subset after 24 weeks of treatment, which was associated with increased mRNA
      levels. A lower increase was observed in CC-chemokine receptor (CCR)-5 expression
      by CD4 T cells. No modifications in the expression of these receptors were
      observed in monocytes and no general increases were observed in mRNA levels of
      chemokine receptors CCR-1, CCR-2b and CCR-3 in IL-2-treated patients.
      CONCLUSIONS: IL-2 at doses that significantly increase CD4 cell counts does not
      induce dramatic modifications in the chemokine/chemokine receptor system. Only
      expression of CXCR-4 appears to increase, due in part to lymphocyte activation.
      Therefore, the efficacy of IL-2 treatment in HIV-1 infection has to be evaluated
      by its ability to activate and induce faster regeneration of the immune system.

PMID- 10203378
TI  - Management of chronic hepatitis C in HIV-infected patients.

PMID- 10203380
TI  - Natural immunity and HIV disease progression.
AB  - OBJECTIVE: To investigate the clinical implications of impaired levels of the
      natural immunity mediated by natural killer (NK) cells and lymphokine activated
      killer (LAK) cells during infection with HIV-1. DESIGN: Data used were from 172
      individuals with an estimated measure of NK cell activity and 146 with an
      estimated measure of LAK cell activity. Patients had active HIV infection at the
      time of enrolment in the study and have been followed-up prospectively for a
      median of 3.0 years. METHODS: The lytic activity of NK cells and LAK cells, the
      CD4 T lymphocyte count, and the concentration of CD16/CD56 NK cells were measured
      at enrolment. HIV RNA in plasma was measured retrospectively. Survival analysis
      was performed considering three main endpoints: CD4 cell counts below 100 x 10(6)
      cells/l, clinical AIDS, and death. RESULTS: In unadjusted analysis and after
      adjustment for age, CD4 T lymphocyte count and plasma HIV RNA at enrolment, low
      LAK cell activity was significantly associated with higher risk of progression to
      a CD4 T lymphocyte count < 100 x 10(6) cells/l (crude P = 0.001; adjusted P =
      0.04) and to death (crude P = 0.0002; adjusted P = 0.02). Patients with low NK
      cell responsiveness to interferon-alpha tended to be at higher risk of death
      (crude P = 0.04; adjusted P = 0.13) whereas unstimulated NK cell activity and the
      concentration of NK cells were of no prognostic value for patients in this
      cohort. CONCLUSIONS: The present study suggests that low LAK cell activity and
      low NK cell responsiveness to interferon-alpha may be important in the
      pathogenesis of HIV infection.

PMID- 10203381
TI  - An evaluation of HIV RNA and CD4 cell count as surrogates for clinical outcome.
      Delta Coordinating Committee and Virology Group.
AB  - OBJECTIVES: To evaluate the role of viral load, as measured by HIV-1 RNA, and CD4
      cell counts as surrogates for clinical outcome using the data from the Delta
      trial. METHODS: A total of 1280 participants (40% of the 3207 participants in the
      Delta trial) with baseline and at least one other serum sample stored at -70
      degrees C were included in the extended virology study, of whom 411 were
      allocated to zidovudine (ZDV) alone, 439 to ZDV plus didanosine (ddl) and 430 to
      ZDV plus zalcitabine (ddC). The extent to which changes in HIV or CD4 cell levels
      up to week 32 can explain the benefit of combination therapy was investigated by
      fitting these marker levels in addition to allocated treatment to Cox
      proportional hazards models for time to death and to disease progression.
      FINDINGS: RNA at baseline and changes at weeks 8, 16 and 32 were independent and
      highly significant predictors of disease progression or death. The hazard of
      progression was increased fourfold (P < 0.0004) for each log10 higher baseline
      RNA and was reduced by 43% (P = 0.004) and by 38% (P = 0.002) for each log10
      reduction at weeks 8 and 16, respectively. Compared with ZDV monotherapy, the
      progression rate was reduced by 43% (P = 0.0001) by ZDV plus ddl and by 36% (P =
      0.001) by ZDV plus ddC. After adjusting for RNA up to week 16, however, there was
      a highly significant treatment effect favouring ZDV monotherapy, which was not
      explained by RNA: the adjusted progression rates were 66% higher (P = 0.005) for
      ZDV plus ddl and 67% higher (P = 0.004) for ZDV plus ddC compared with ZDV alone.
      In contrast, after adjusting for CD4 to week 16 there remained a significant
      treatment effect favouring combination therapy: compared with ZDV monotherapy,
      the progression rate was reduced by 29% (P < 0.0001) by ZDV plus ddl and 12% (P =
      0.1) by ZDV plus ddC. Adjustment for both RNA and CD4 to week 16 resulted in a
      relative increase in the hazard of progression (49% (P = 0.04) for ZDV plus ddl
      and 37% (P = 0.09) for ZDV plus ddC) not explained by the two markers combined.
      CONCLUSION: Clinical benefit from combinations of ZDV plus ddl or ZDV plus ddC
      was underestimated by CD4 cell counts and overestimated by RNA levels and by the
      two markers combined. Neither HIV RNA levels nor CD4 cell counts appear to be
      complete surrogates for clinical outcome.

PMID- 10203382
TI  - Predictors of survival and eradication of Mycobacterium avium complex bacteremia
      (MAC) in AIDS patients in the Canadian randomized MAC treatment trial. Canadian
      HIV Trials Network Protocol 010 Study Group.
AB  - OBJECTIVE: To assess the importance of baseline characteristics including medical
      history, indicators of current disease status, therapeutic drug use, in vitro
      drug susceptibility, immune status and mycobacterial load on bacteriologic
      response and survival in HIV-positive patients with Mycobacterium avium complex
      (MAC) bacteremia. DESIGN: An observational substudy of an open-label randomized
      controlled trial of two alternative therapeutic regimens for MAC. SETTING: Twenty
      four hospital-based HIV clinics in 16 Canadian cities. MAIN OUTCOME MEASURES: The
      main outcome measures were survival and bacteriologic response, defined by
      consecutive negative blood cultures for MAC at least 2 weeks apart within 16
      weeks of study entry. RESULTS: Prior AIDS diagnosis, low Karnofsky score, active
      unstable AIDS-related conditions, absence of antiretroviral therapy and absence
      of Pneumocystis carinii pneumonia prophylaxis were associated with shorter
      survival by univariate regression using the proportional hazards model. On
      multivariate analysis, antiretroviral therapy was not an independent predictor of
      mortality, and previous rifabutin prophylaxis was independently associated with
      poor survival outcomes, a result consistent across study treatment. Using a
      logistic regression model, baseline quantitative mycobacterial load [relative
      odds of clearing, 1.97 for a decrease of 1 log10 colony forming count; 95%
      confidence interval (CI), 1.36-2.87; P < 0.001] and Karnofsky score were the only
      statistically significant univariate predictors of clearance, although previous
      prophylaxis with rifabutin was also a significant predictor in a multivariate
      model (relative odds of clearing, 0.39; 95% CI, 0.17-0.88; P < 0.05).
      CONCLUSIONS: This study indicates that although the level of MAC bacteremia is an
      important predictor of clearance, it is not associated with survival.

PMID- 10203383
TI  - Stable antenatal HIV-1 seroprevalence with high population mobility and marked
      seroprevalence variation among sentinel sites within Nairobi, Kenya.
AB  - OBJECTIVES: To monitor and analyse trends in HIV-1 seroprevalence among antenatal
      women in Nairobi, Kenya. DESIGN: Six sequential surveys were carried out among
      antenatal clinic attenders at four Nairobi City Council health centres between
      November 1991 and April 1997. METHODS: A total of 6828 women attending for first
      antenatal clinic visit were administered a standard questionnaire to obtain
      demographic information and were screened for HIV-1. RESULTS: HIV-1
      seroprevalence rose from 12.1% in the first survey to 16.2% in the third,
      completed in October 1993. No rise was observed in subsequent surveys, and
      seroprevalence among women under the age of 20 declined after the third survey.
      Significant differences in seroprevalence (P < 0.001) were observed in all survey
      rounds between women who reported that their province of origin was Nyanza (22.4%
      overall), compared with those from other provinces in western Kenya (14.1%), and
      the eastern group of provinces (8.9%). The rise in HIV-1 seroprevalence observed
      between 1991 and 1993 was almost entirely attributable to the rising
      seroprevalence among women from Nyanza. There were considerable differences in
      HIV-1 seroprevalence among the four health centres, partly accounted for by
      differences in the proportion of clinic attenders from different provinces of
      origin, which also changed significantly over time. CONCLUSIONS: HIV-1
      seroprevalence has stabilized in antenatal women attending these health centres
      in Nairobi, and may be declining among women in the youngest age group. This may
      reflect stabilization of HIV-1 incidence, but further observation is required.
      The levels of infection among Nairobi residents reflect the evolution of the HIV
      epidemic in their provinces of origin, and changing client composition influences
      HIV-1 seroprevalence at different clinics. HIV sentinel surveillance should be
      carried out at multiple sites in large urban centres to monitor accurately the
      evolution of the HIV epidemic and the impact of control efforts in reducing
      transmission.

PMID- 10203384
TI  - Sexual, contraceptive, and drug use behaviors of women with HIV and those at high
      risk for infection: results from the Women's Interagency HIV Study.
AB  - OBJECTIVE: To document the sexual and contraceptive practices of women with HIV
      infection or who are at risk for infection. DESIGN: Data on the baseline
      behaviors of 561 HIV-negative and 2040 HIV-positive women were collected as part
      of the Women's Interagency HIV Study (WIHS). WIHS is a multisite, longitudinal
      study following the natural history of HIV infection among women in the United
      States. METHODS: Each participant contributed an interviewer administered, self
      report interview including questions on sexual and contraceptive behavior.
      RESULTS: Women with HIV were less likely to report heterosexual activity in the
      previous 6 months (65% HIV-positive, 76% HIV-negative). Among sexually active
      women, there were no differences in the proportion of those reporting vaginal
      (97% HIV-positive, 98% HIV-negative) or anal sex (12% HIV-positive, 10% HIV
      negative), although women with HIV were less likely to report cunnilingus (41%
      HIV-positive, 70% HIV-negative) and fellatio (48% HIV-positive, 57% HIV
      negative). Of women with HIV, 63% always used condoms during vaginal sex (versus
      28% HIV-negative), with lower rates reported during other sexual activities.
      Crack, cocaine, or injecting drug use, reported by 27% of HIV-positive and 35% of
      HIV-negative women, was associated with inconsistent condom use, independent of
      serostatus. HIV-positive women who reported using condoms and another
      contraception method were less consistent condom users (57% consistent versus
      67%). CONCLUSIONS: The prevalence of sexual risk behavior in this sample suggests
      that, although women with HIV exhibit lower levels of sexual risk behavior than
      uninfected women, many have not been successfully reached with regard to
      implementing safer behaviors. These findings have implications for more
      widespread and effective behavioral intervention efforts.

PMID- 10203385
TI  - Nosocomial infections in HIV infected patients. Gruppo HIV e Infezioni
      Ospedaliere.
AB  - OBJECTIVES: To determine the incidence of nosocomial infections (NI) in HIV
      infected patients and to analyse some of the associated risk factors. DESIGN AND
      SETTING: Multicentre prospective study on consecutive HIV-infected patients
      admitted to 19 Italian acute-care infectious disease wards. METHODS: All patients
      admitted during a 1-year period were followed-up for NI until their discharge.
      Univariate and multivariate analyses were performed for NI risk factors. RESULTS:
      As of June 1998 a total of 344 NI occurred in 4330 admissions, with at least one
      NI in 273 admissions (6.3%). The incidence rate of NI was 3.6 per 1000 patient
      days [95% confidence interval (CI), 3.2-4.1]. Overall distribution by site was
      36.6% bloodstream infections (BSI), 30.5% urinary tract infections, 18.4%
      pneumonia, 5.2% skin/soft tissue infections, 2.0% surgical wound infections and
      7.3% others. Fifty-five out of the 126 BSI were related to a central venous
      catheter (CVC); the rate of CVC-associated infections was eight infections per
      1000 devices. At multivariate analysis, variables independently associated with
      NI included CD4 T-lymphocyte count < 200 x 10(6)/l [odds ratio (OR), 2.21; 95%
      CI, 1.35-3.62], Karnofsky Performance Status < 40 (OR, 1.89; 95% CI, 1.28-2.78),
      therapy with corticosteroids (OR, 1.78; 95% CI, 1.29-2.45), CVC (OR, 3.24; 95%
      CI, 2.41-4.35), urinary catheter (OR, 6.53; 95% CI, 4.81-8.86) and surgery (OR,
      3.13; 95% CI, 1.90-5.15). CONCLUSIONS: Results suggest that NI occur commonly in
      HIV-infected patients. As the number of cases of HIV continues to increase, the
      number of HIV-infected patients requiring hospitalization may also increase.
      Clinicians need to be aware of the risk factors for NI and must consider these
      infections in the overall management of HIV-infected, hospitalized patients.

PMID- 10203386
TI  - Cofactors for the acquisition of HIV-1 among heterosexual men: prospective cohort
      study of trucking company workers in Kenya.
AB  - OBJECTIVE: To determine the prevalence, incidence, and correlates of HIV-1
      infection in a cohort of east African trucking company employees. METHODS: HIV-1
      seronegative trucking company employees were enrolled in a prospective cohort
      study and evaluated at 3 monthly intervals for HIV-1 seroconversion, sexually
      transmitted diseases, and sexual behavior. RESULTS: The baseline seroprevalence
      of HIV-1 among 1500 trucking company employees was 17.8%. Among 752 HIV-1
      seronegative men who were followed, the HIV-1 annual seroincidence was 3.1%. In
      univariate analysis, HIV-1 acquisition was associated with age under 25 years, 10
      years or less of sexual activity, occupation as a driver/driver's assistant,
      occupational travel for more than 14 days per month, religion other than
      Christian or Muslim, uncircumcised status, sex with a prostitute, sex with a
      girlfriend/casual partner, extramarital sex, and enrollment seropositivity to
      Treponema pallidum, Haemophilus ducreyi, and Herpes simplex virus type 2 (all P
      values < or = 0.05). Using multivariate analysis, HIV-1 acquisition was
      independently associated with 10 years or less of sexual activity (hazard rate
      ratio (HRR) 2.0, 95% confidence interval (CI) 1.0-4.3), occupation as a
      driver/driver's assistant (HRR 3.9, 95% CI 1.7-9.0), religion other than
      Christian or Muslim (HRR 6.1, 95% CI 1.4-25.7), uncircumcised status (HRR 2.3,
      95% CI 1.0-5.0), and unprotected sex with a prostitute (HRR 2.8, 95% CI 1.1-7.0).
      CONCLUSIONS: Trucking company employees had a high HIV-1 seroprevalence rate at
      enrollment and a high HIV-1 seroincidence during follow-up. Risk factors for HIV
      1 seroconversion included years of sexual activity, occupation, religion,
      uncircumcised status, and unprotected sex with a prostitute. This population is
      an appropriate target for HIV-1 prevention trials and behavioral interventions.

PMID- 10203387
TI  - Evidence of exogenous reinfection and mixed infection with more than one strain
      of Mycobacterium tuberculosis among Spanish HIV-infected inmates.
AB  - BACKGROUND: As prisons have a high prevalence of tuberculosis and HIV infection,
      we studied the possibility of multiple tuberculosis infections in a selected
      population of HIV-infected inmates. METHODS: Two groups of patients with special
      characteristics were selected from 226 HIV-infected inmates diagnosed with
      tuberculosis in the prisons of Madrid (Spain) between 1993 and 1994. The first
      group contained nine patients who remained culture positive 4 months after the
      initiation of therapy and the second group contained 28 patients with
      Mycobacterium tuberculosis isolated from different anatomical sites. DNA typing
      with IS6110 was performed on all isolates from these patients. In some patients a
      secondary DNA typing with the plasmid pTBN12 was performed. RESULTS: Two patients
      from group A had a second M. tuberculosis strain obtained 4 and 18 months after
      the initial isolate, with different IS6110 and pTBN12 patterns. In one patient
      the second strain was multidrug resistant and in the other patient both strains
      had the same drug-susceptible pattern. The clinical and microbiologic evidence in
      both patients was consistent with the presence of active tuberculosis caused by a
      new strain of M. tuberculosis. In group B, the isolates from 27 patients shared
      similar fingerprint pattern; however, in one patient isolates from sputum and
      urine showed different IS6110 and pTBN12 patterns, although both strains showed
      the same drug-susceptible phenotype. CONCLUSION: This study provides evidence
      that HIV-infected inmates living under conditions of high environmental
      infectivity can be infected with two different strains of M. tuberculosis. This
      finding has implications for the tuberculosis-control programs in prison.

PMID- 10203388
TI  - CD4+CD7-lymphocyte subset is expanded in HIV-infected patients with low CD4 cell
      count rescue during highly active antiretroviral therapy.

PMID- 10203390
TI  - Early diagnosis of acquired ocular syphilis requires a high index of suspicion
      and may prevent visual loss.

PMID- 10203389
TI  - Acute porphyria following commencement of indinavir.

PMID- 10203391
TI  - CC-chemokine receptor variants, SDF-1 polymorphism, and disease progression in
      720 HIV-infected patients. SEROCO Cohort. Amsterdam Cohort Studies on AIDS.

PMID- 10203392
TI  - Frequent cervicovaginal shedding of HIV-1 in asymptomatic, non-severely
      immunodeficient women.

PMID- 10203393
TI  - High prevalence of multiple drug resistance mutations in a UK HIV/AIDS patient
      population.

PMID- 10203394
TI  - Clinical improvement of HIV-associated psoriasis parallels a reduction of HIV
      viral load induced by effective antiretroviral therapy.

PMID- 10203395
TI  - Use of dried whole blood spots for quantification of HIV-1 RNA.

PMID- 10203396
TI  - A reappraisal of mouth-to-mouth ventilation during bystander-initiated
      cardiopulmonary resuscitation. A statement for healthcare professionals from the
      Ventilation Working Group of the Basic Life Support and Pediatric Life Support
      Subcommittees, American Heart Association.

PMID- 10203397
TI  - Determinants of reluctance to perform CPR among residents and applicants: the
      impact of experience on helping behavior.
AB  - BACKGROUND: Though mouth-to-mouth resuscitation (MMR) is widely endorsed as a
      useful lifesaving technique, studies have shown that health care professionals
      are reluctant to perform it. To characterize the circumstances which facilitate
      this reluctance among physicians, we have surveyed current and future residency
      trainees regarding attitudes toward providing ventilation by this method to
      strangers experiencing arrest in the community. METHODS: A total of 280
      categorical emergency medicine (EM) and internal medicine (IM) house officers and
      respective program applicants at a 655 bed Brooklyn, New York teaching hospital
      were anonymously surveyed regarding their willingness to attempt resuscitation in
      five hypothetical scenarios of cardiopulmonary arrest. RESULTS: A direct
      relationship was observed between residency training level and reluctance to
      perform MMR in each scenario. Applicants expressed greater overall willingness to
      perform MMR than all residents (56 versus 34%, P < 0.00001). Willingness among
      experienced residents was lower than for junior-level residents (29 versus 40%, P
      = 0.01). EM and IM physicians were statistically indifferent in their responses.
      There were no differences in willingness to perform MMR by age in MD applicant or
      resident groups. CONCLUSIONS: Many physicians and future doctors are reluctant to
      perform MMR on arrest victims in the community, a trend that increases in
      prevalence among those with more residency training. These data support the
      hypothesis that diminished helping behavior occurs gradually over the training
      period and may occur as a direct consequence of the training experience. A model
      for characterizing the elements that make up a rescuer's decision process is
      proposed.

PMID- 10203398
TI  - Do victims of an out-of-hospital cardiac arrest benefit from a training program
      for emergency medical dispatchers?
AB  - In this paper, we assessed the effects of a training course for emergency medical
      dispatchers on the handling of out-of-hospital cardiac arrest cases in the
      dispatch center of a two-tiered emergency medical services system. A total of 112
      cardiac arrest cases were studied; 64 before and 48 after the training course.
      Before the course, all relevant information was obtained in 36% of cases, only
      partial information in 56% and no useful medical information in 8%. The
      corresponding figures after the training program were 62, 38 and 0%, respectively
      (2 x 3 chi2 test, P = 0.01). Trends towards an increase in the percentage of
      cases in which a second-tier team was sent immediately after the initial call (58
      vs 75%; chi2 test, P = 0.06) and towards shorter overall intervals between
      receipt of the call and dispatch of the second-tier team (logrank test, P = 0.10)
      were noticed. Similarly, the survival rate increased from 2% before, to 8% after
      the training course (chi2 test with Yates' correction, P = 0.24). We conclude
      that our training program for emergency medical dispatchers produced some
      beneficial effects.

PMID- 10203399
TI  - Improved retention of the EMS activation component (EMSAC) in adult CPR
      education.
AB  - This study was undertaken to determine whether using a model-telephone to
      simulate the emergency medical services activation component (EMSAC) during adult
      cardiopulmonary resuscitation (CPR) training practice would lead to better
      retention of this component during end-of-class assessment. In a prospective
      randomized manner, 233 medical professionals and lay-persons taking American
      Heart Association (AHA) CPR classes were evaluated for EMSAC retention during CPR
      skills performance at the end of class. During the assessment correct versus
      incorrect activation of EMS was noted. Subject response by age, exposure to
      previous CPR training, and medical professional or lay-person status was
      examined. Differences in results among instructors also were examined. Overall,
      those in the group using the model-telephone remembered to activate EMS correctly
      more frequently than those in the group not using the phone (69 vs 52%, P =
      0.009). The < 30 age group was unaffected by the use of the phone (P = 0.85). The
      group between 30 and 50 years of age did significantly better with the use of the
      phone (P = 0.007), as did those 50 years of age and older (P = 0.03). Previous
      CPR training did not affect the response (P = 0.18). We conclude that use of the
      model-telephone improved EMSAC retention significantly overall except in the < 30
      year-old age group. We recommend using the model-telephone in future adult CPR
      classes.

PMID- 10203400
TI  - Comparison of two emergency response systems and their effect on survival from
      out of hospital cardiac arrest.
AB  - The pre-hospital care provided by emergency response systems will have an effect
      on the outcome of patients who have sustained an out of hospital cardiac arrest.
      This study compares the results of resuscitation in two centres, one in the UK
      (Edinburgh) and the other in the USA (Milwaukee), and examines the demographics
      in both centres. An overall greater proportion of patients survived to hospital
      discharge in Edinburgh, 12.4%, compared with 7.2% in Milwaukee (P < 0.01).
      However patients were more likely to have a witnessed collapse in Edinburgh
      65.7%, compared with 25% (P < 0.001) and significantly more of those patients
      received bystander cardiopulmonary resuscitation (CPR) 42.3%, compared with 27.1%
      (P < 0.005). When these two effects are accounted for there is no difference in
      outcome. The importance of early alerting of emergency services and early
      bystander CPR should not be underestimated.

PMID- 10203401
TI  - Quality of life after cardiopulmonary resuscitation.

PMID- 10203402
TI  - Magnesium in cardiac arrest (the magic trial).
AB  - The prognosis of out of hospital cardiac arrest (OHCA) is dismal. Recent reports
      indicate that high dose magnesium may improve survival. A prospective randomized
      double blind placebo controlled trial was conducted at the emergency department
      (ED) of Royal Perth Hospital, a University teaching hospital. Patients with OHCA
      of cardiac origin received either 5 g MgSO4 or placebo as first line drug
      therapy. The remainder of their management was standard advanced cardiac life
      support (ACLS). Study endpoints were: (1) ECG rhythm 2 min after the trial drug;
      (2) return of spontaneous circulation; (3) survival to leave the ED; (4) survival
      to leave intensive care; and (5) survival to hospital discharge. Of 67 patients
      enrolled, 31 received magnesium and 36 placebo. There were no significant
      differences between groups for all criteria, except that there were significantly
      more arrests witnessed after arrival of EMS personnel in the magnesium group (11
      or 35% vs 4 or 11%). Return of spontaneous circulation occurred in seven (23%)
      patients receiving magnesium and eight (22%) placebo. Four patients in each group
      survived to leave the ED and one from the magnesium group survived to hospital
      discharge. There were no survivors in the placebo group. In this study, the use
      of high dose magnesium as first line drug therapy for OHCA was not associated
      with a significantly improved survival. Early defibrillation remains the single
      most important treatment for ventricular fibrillation (VF). Further studies are
      required to evaluate the role of magnesium in cardiac and cerebral resuscitation.

PMID- 10203404
TI  - Nasal route to ventilation during basic cardiopulmonary resuscitation in children
      under two months of age.
AB  - In order to determine the feasibility of performing mouth to mouth and nose
      resuscitation according to the established guidelines, a study was carried out on
      the facial dimensions of 40 children under 2 months of age (20 under 1 month and
      20 aged 1 month) and the open-mouth dimensions of the 40 adults in charge of
      these children. Only nine adults in charge of children under 1 month of age would
      have been able to seal the mouth and nose of these infants. In the case of the 1
      month old infants, only one adult (5%) proved able to encircle the mouth and
      nose. Strikingly, none of the adults involved in this study would have been able
      to perform the ventilation manoeuvres in children with open mouths as recommended
      by the American Heart Association and European Resuscitation Council guidelines.
      In conclusion, since adults are unable to cover with their mouths both the mouth
      and nose of the infants, the nasal route to ventilation, with oral sealing of the
      nose, is recommended as the best approach for the practice and teaching of the
      basic cardiopulmonary resuscitation (CPR) in children under 2 months of age who
      have respiratory arrest.

PMID- 10203403
TI  - Experience of an emergency mobile asthma treatment programme.
AB  - In order to reduce mortality and the need for hospital care for patients
      suffering from acute asthma, an emergency programme was set up. An ambulance
      crew, trained in coronary-pulmonary resuscitation was instructed in dealing with
      acute asthma and delegated to give 24 h treatment with bronchodilators (inhaled
      salbutamol and ipratropium bromide). If there was no, or only slight, improvement
      with this therapy, nurses (daytime) were delegated to give injections with
      corticosteroids (terbutaline and theophylline). Over a period of 2 years, 240
      patients, 115 women and 125 men, were treated on 367 occasions. In 127 patients
      (53%), two or more treatments were given. The number of times treatment was
      given, as well as the proportion of females to males, increased the younger the
      patients were. Out of all the cases, more than 70% improved after treatment. On
      arrival, 21 patients (6%) were unconscious. After therapy, 15/21 patients (71%)
      survived. This may correspond to a similar reduction in mortality (population
      about 350,000 inhabitants), as it is unlikely that unconscious patients can
      survive without intensive care.

PMID- 10203405
TI  - Fat necks: modification of a standard surgical airway protocol in the pre
      hospital environmental.
AB  - We report two cases of trauma where a surgical airway was required. In both cases
      soft tissue swelling of the neck made modification of the Advanced Trauma Life
      Support (ATLS) airway guidelines necessary. A gum elastic bougie was used to
      guide a standard endotracheal tube into a cricothyroidotomy incision and secure
      the airway. Slight departure from standard techniques may be required in
      difficult circumstances to achieve a definitive airway.

PMID- 10203406
TI  - The mechanism of blood flow in cardiopulmonary resuscitation--introducing the
      lung pump.
AB  - The mechanism of blood flow in cardiopulmonary resuscitation remains
      controversial. Inconsistencies in the cardiac pump model necessitated the
      development of the thoracic pump. Neither hypothesis alone can account for blood
      flow during external massage. Using the postulates that a cyclical pump has three
      components, an inlet valve, a compression chamber and an outlet valve, we propose
      the lung pump hypothesis where these components are represented by the pulmonary
      valve; the lung vasculature/left atrium/left ventricle; and the aortic valve. We
      explore the mechanism and effect of this hypothesis and match it to previous
      observations. The implications to cardiopulmonary resuscitation are addressed.

PMID- 10203407
TI  - Force distribution across the heel of the hand during simulated manual chest
      compression.
AB  - According to most published guidelines of cardiopulmonary resuscitation chest
      compression is performed on the lower half of the sternum by compressing the
      sternum with the heel of one hand and the other hand on top of the first. In all
      guidelines and during CPR training great importance is attributed to exact
      localisation of the so-called compression point. In a laboratory investigation we
      assessed the force distribution across the heel of the hand and defined the total
      breadth in contact with the sternum. In order to find out whether there is any
      difference in the force pattern with the right or the left hand in direct contact
      with the sternum we determined the resultant maximal force of that part of the
      heel of the hand exerting the maximal force. A total of 12 anaesthetists
      performed simulated chest compressions onto a flat surface covered with an
      integrated force sensor mat. The distance between the most ulnar part and the
      most radial part of the hand was determined to be 9.2 cm. Similar mean total
      forces were measured (right hand in contact: 644 N; left hand in contact: 621 N).
      In all except one anaesthetist the hypothenar part of the heel exerted a
      significantly higher force compared to the thenar part, independent of whether
      the right hand or the left hand was in contact. The distance between points of
      maximal force when the right hand or when the left hand in contact was 2.2 cm
      corresponding to the breadth of one and a half fingers. To reduce the potential
      risk of sternal fractures by chest compressions applied too far in a cephalad
      direction, we recommend use of the right hand in contact if the rescuer kneels at
      the right side of the patient and vice versa.

PMID- 10203408
TI  - Synergistic effects of vasopressin plus epinephrine during cardiopulmonary
      resuscitation.
AB  - Both epinephrine (Epi) and vasopressin (VP) increase coronary perfusion pressure
      (CPP) when administered during cardiac arrest. Given their different mechanisms
      of action we tested the hypothesis that during cardiopulmonary resuscitation
      (CPR) a combination of VP plus Epi would be superior to either agent alone.
      Epi(40 microg/kg), VP(0.3 U/kg) and the combination of both agents were assessed
      in a porcine model of ventricular fibrillation (VF). Maximum CPP (diastolic
      aortic-right atrial pressures) during CPR was similar among the groups but the
      time course of action was different in each group: with Epi + VP the increase in
      CPP was significantly more rapid than with VP alone whereas the CPP remained
      significantly higher for a longer periods of time with VP or VP + Epi versus Epi
      alone. Left ventricular blood flow (ml/min per g) determined during CPR two min
      after drug administration was similar between groups: Epi 1.06 +/- 0.16; VP 0.82
      +/- 0.26; Epi + VP 0.83 +/- 0.14 (P = N.S.). Post drug administration. 2 min,
      cerebral blood flow (ml/min per g) in the VP group (0.76 +/- 0.15) was more than
      two times higher compared with Epi alone (Epi:0.30 +/- 0.08, P < 0.01 versus VP)
      and Epi plus VP (Epi + VP:0.23 +/- 0.03, P < 0.01 versus VP). We conclude that
      combination of VP + Epi during cardiac arrest results in a more rapid rise in CPP
      when compared with VP alone and a more sustained elevation in CPP than observed
      with Epi alone. Thus, the synergistic effects of these two potent vasopressor
      agents may be of benefit during CPR.

PMID- 10203409
TI  - The use of the Haemonetic Rapid Infusion System (RIS) has dramatically reduced
      the duration and frequency of significant intraoperative hypotension and
      hypothermia that can occur in major cases.

PMID- 10203410
TI  - Clinical validation of a new immunoradiometric assay for intact human
      osteocalcin.
AB  - The purpose of this study was to estimate clinical validity of a new available
      immunoradiometric assay for circulating intact human BGP (N-tact Osteo SP) by
      measuring this protein in a large number of normal subjects and patients with the
      most common metabolic bone diseases. One hundred normal subjects were studied in
      order to obtain our normal ranges (4.9 +/- 1.7 ng/ml). The mean values found in
      28 patients with primary hyperparathyroidism (17.5 +/- 22.8 ng/ml, P < 0.001), 15
      glucocorticoid-treated patients (1.9 +/- 1.5, P < 0. 001), 10 patients with
      hypoparathyroidism (1.5 +/- 0.7, P < 0.001), 9 with hyperthyroidism (8.3 +/- 3.8,
      P < 0.001), 8 with skeletal metastases (7.2 +/- 2.3, P < 0.001), and 4 with
      humoral hypercalcemia of malignancy (2.42 +/- 1.91, P < 0.005) were significantly
      different from mean values found in normal subjects. Mean decrease of serum
      osteocalcin T-score values was significantly greater when evaluated by N-tact
      Osteo SP assay in 15 steroid-treated patients (-1.4 +/- 1.0) and 19 primary
      hyperparathyroid (PHPT) patients (3.6 +/- 1.9), compared with the mean values
      obtained with the Elsa-Osteo assay (-0.67 +/- 1.2, P < 0. 002 and 4.3 +/- 2.8, P
      < 0.04, respectively). We found significant correlations between the global
      skeletal uptake of 99mTc-methylendiphosphonate and serum BGP levels assayed by
      both N-tact Osteo SP (P < 0.01) and Elsa-Ost-Nat assay (P < 0.05). Our results
      indicate that this new immunoradiometric assay for the intact human osteocalcin
      has the potential for good discrimination between normal subjects and patients
      with both low and high bone turnover. Furthermore, our findings emphasize the
      fact that, in the absence of available standardized commercial assays, one should
      rely on only one assay because different results are obtained by different assays
      under different clinical conditions.

PMID- 10203411
TI  - Persistence of bone collagen cross-links in skeletons of the Nuraghi population
      living in Sardinia 1500-1200 B.C.
AB  - Bone collagen has a specific molecular ultrastructure which can be proved by
      birefringence. This protein, forming the main organic component of bone tissue,
      is known to survive millennia in paleontological bones and teeth. Birefringence
      of bone collagen obtained from the skeletons of the Nuraghi population living in
      Sardinia c-ca 1500 years B.C. was found previously by the use of polarizing
      microscopy [1]. In this paper, using high pressure liquid chromatography (HPLC)
      techniques, we show the existence of bone collagen cross-links preserved in
      Nuraghi skeletons after more than 3000 years.

PMID- 10203412
TI  - Bone mineral density in flatwater sprint kayakers.
AB  - To elucidate the possible skeletal benefits of the muscular contractions and the
      nonweight-bearing loading pattern associated with kayaking, we investigated the
      bone mineral density (BMD, g/cm2) of 10 elite kayakers, six males and four
      females, with a median age of 19 years. Each subject was compared with the mean
      value of two matched controls. BMD of the total body, head, ribs, humerus, legs,
      proximal femur (neck, wards, trochanter), spine, lumbar spine, and bone mineral
      content (BMC, g), of the arms was obtained using a dual energy X-ray
      absorptiometer (DXA). Body composition was also assessed. The kayakers had a
      significantly (P < 0.05-0.01) greater BMD in most upper body sites: left and
      right humerus (10.4% and 11. 7%), respectively, ribs (6.4%), spine (10.9%), and a
      greater BMC of the left and right arm (15.7% and 10.6%, respectively). No
      significant differences in the BMD of the total body, head, or any of the lower
      body sites were found, except for the pelvis, which was significantly greater in
      kayakers (5.1%). The controls had a significantly lesser lean body mass (10.4%)
      and greater percentage of body fat (19.5%) than the kayakers. Bivariate
      correlation analysis in the controls demonstrated significant and strong
      relationships between BMD in upper body sites and lean body mass, weight, and
      fat; the effects of training seem to outweigh most such relationships in
      kayakers. In conclusion, it seems that the loading pattern and muscular
      contractions associated with kayaking may result in site-specific adaptations of
      the skeleton.

PMID- 10203413
TI  - Influence of weight gain on spine mineral density in postmenopausal women.
AB  - We studied the relationships between weight variables and spine bone mineral
      density (BMD) in 183 postmenopausal women aged 34-76 years. There was a
      significant positive correlation of current body mass index (cBMI) and % of ideal
      body weight (IBW) with BMD. Moreover, the increase in BMI and % IBW was also
      positively and significantly associated with a higher age-adjusted lumbar BMD.
      Weight gain, estimated as the difference between current body weight and past
      "ideal" body weight, was associated with significant age-adjusted BMD with a
      threshold of 17%, and postmenopausal women with a gain of over 17% had
      significantly higher spine BMD.

PMID- 10203414
TI  - The effectiveness of cyclic and continuous oral clodronate therapy on bone
      density and markers in osteopenic postmenopausal women.
AB  - Bisphosphonates have been used effectively to treat established osteoporosis and
      prevent postmenopausal bone loss. However, the optimal manner of its
      administration-whether cyclic or continuous-has not been well established. This
      study investigated the efficacy of cyclic and continuous oral administration of
      clodronate in 54 newly identified osteopenic postmenopausal women in a
      randomized, double-blind, crossover fashion. The participants were randomly
      separated into two groups. The cyclic group (n = 29) received 800 mg twice daily
      of oral clodronate for 2 weeks every 3 months for the first 12 months followed by
      placebo for the second 12 months. The continuous group (n = 25) received placebo
      in the first 12 months and ingested 400 mg of clodronate once daily for the
      second 12 months. The urinary amino-terminal (NTXtrade mark) and carboxy-terminal
      (CrossLapstrade mark) cross-linked fragments of type I collagen, both markers of
      bone resorption, showed a marked decrease (25-50%) with both regimens during the
      period of active treatment. In the cyclic group, the levels of these two markers
      increased in the second 12 months with placebo, but did not return to the
      baseline completely. However, bone mineral density (BMD), determined by dual
      energy X-ray absorptiometry (DXA), showed no significant change of BMD at various
      sites after 1 year of active treatment in both groups. Thoracic and lumbar spine
      X-ray showed no new vertebral fracture in either group after 2 years of
      treatment. With the two treatment protocols in this study, oral clodronate was
      effective in decreasing postmenopausal bone resorption, causing no significant
      changes in BMD at various sites.

PMID- 10203415
TI  - The effects of 10 weeks military training on heel ultrasound and bone turnover.
AB  - To measure the physiological changes in bone in response to strenuous exercise we
      performed a prospective study of male army recruits over 10 weeks of basic
      training. Measurements performed at the start and completion of training
      consisted of ultrasound (US) measurements of the heel: velocity of sound (VOS in
      m/seconds) and broadband ultrasound attenuation (BUA in dB/MHz) and bone turnover
      markers; osteocalcin (OC), bone-specific alkaline phosphatase (BALP), and
      tartrate-resistant acid phosphatase (TRAP). Forty subjects were recruited for the
      study and 26 completed training. Over the 10-week study period there was a
      significant 1.7% fall in mean VOS [mean paired difference (mpd) 27.2 m/second,
      SEM 9.5 (95% CI 7.5-46.8) P = 0.009] and a nonsignificant 3.4% increase in BUA (P
      = 0.159). There were significant falls in markers of bone formation OC [11.6%,
      mpd 0. 11 microg/liter (95% CI 0.07-0.14) P < 0.001] and BALP [13.3%, mpd 3. 49
      U/liter (CI 0.80-6.18) P = 0.013] and a nonsignificant 9.5% fall in TRAP a marker
      of bone resorption. The 10 recruits subsequently injured had a significantly
      lower VOS on entry [mean difference 24.2 m/seconds (95% CI 4.6-43.7) P = 0.017]
      and nonsignificantly raised BUA and baseline levels of all bone markers. The
      ultrasound changes may be accounted for by increase in trabecular separation and
      a fall in trabecular connectivity due to microfracture. The decrease in bone
      markers implies a fall in bone turnover.

PMID- 10203416
TI  - Genomic insertion of the SV-40 large T oncogene in normal adult human trabecular
      osteoblastic cells induces cell growth without loss of the differentiated
      phenotype.
AB  - In the present study, we established a new adult human trabecular osteoblastic
      (AHTO) cell line, immortalized by SV-40 Large T (LT) oncogene. From seven
      proliferative colonies identified, we selected clone 7 with high alkaline
      phosphatase (ALP) activity for further analysis. AHTO-7 cells were able to grow
      for at least 8 months and 25 passages, with a doubling time of about 22 hours.
      Immunocytochemistry staining and RT-PCR analysis indicated that the extended life
      span of AHTO-7 cells results in genomic insertion of SV-40 LT oncogene. The cells
      responded to PTH and PGE2 in terms of cAMP accumulation. The time course study,
      in the presence of 10(-8) M vitamin D3 (vit D3) showed a marked increase
      (fourfold) in ALP activity with a peak at day 3. Furthermore, in the presence of
      ascorbic acid (50 microg/ml) and inorganic phosphate (3 mM), AHTO-7 cells
      produced abundant calcified extracellular matrix, as examined by the von Kossa
      staining after 2 weeks of culture. Molecular analysis of mRNAs for phenotypic
      osteoblast markers at day 15 showed the expression of ALP, osteocalcin (OC), and
      collagen type I (Col I) mRNAs constitutively. Col I expression was inhibited by
      vit D3 and dexamethasone treatment. In contrast, treatment with vit D3 induced a
      marked increase of ALP and OC transcripts. Therefore, the immortalized AHTO-7
      cells express osteoblast markers that are induced by calciotropic hormones, and
      constitute a suitable model for identifying specific osteoblastic genes and their
      regulation during human osteoblast differentiation.

PMID- 10203418
TI  - 1,25 dihydroxyvitamin-D3 attenuates the confluence-dependent differences in the
      osteoblast characteristic proteins alkaline phosphatase, procollagen I peptide,
      and osteocalcin.
AB  - In the present study a cell culture model of primary human osteoblasts based on
      degrees of confluence was investigated by measuring basal and
      1,25(OH)2D3stimulated levels of the osteoblast characteristic proteins alkaline
      phosphatase (AP), procollagen I-peptide (PICP), and osteocalcin (OC), as well as
      the corresponding gene expression. Primary osteoblast-like cell cultures from
      seven donors were treated in the second passage with 1,25(OH)2D3 (5 x 10(-8) M
      for 48 hours) and investigated at four stages of confluence (stage I 50%, stage
      II 75%, stage III 100%, and stage IV 7 days postconfluence). In untreated
      cultures passing through the different stages of confluence, we saw a 1.8-fold
      increase of AP activity, a 2. 3-fold increase of OC secretion, but a decrease of
      PICP levels to 0. 36-fold. Gene expression showed only minor variation between
      the different confluence stages. 1,25(OH)2D3 did not significantly affect PICP
      production. Alkaline phosphatase protein was stimulated during proliferation
      until confluence, with no effect thereafter. Surprisingly, OC secretion and mRNA
      expression were stimulated in all four stages to the same absolute level
      independent of basal values. We conclude that our results correspond to other
      studies showing differentiation-stage dependent changes of basal levels of
      osteoblast-specific proteins. However, 1,25(OH)2D3 stimulation decreased the
      confluence-dependent difference for AP and abolished it for osteocalcin, thus
      leading to a more differentiated phenotype of the osteoblast. Therefore,
      1,25(OH)2D3 stimulation might improve the reproducibility of results obtained at
      different confluence stages from cultures of clinical samples.

PMID- 10203419
TI  - Scanning small angle X-ray scattering analysis of human bone sections.
AB  - Scanning small-angle X-ray scattering (scanning SAXS) was applied for the first
      time on bone to compare results from SAXS directly with those from other position
      sensitive methods, such as light and polarized light microscopy, back-scattered
      electron imaging, and radiographic imaging. Since scanning SAXS is a
      nondestructive method of investigation, images from all these techniques could be
      obtained from the same bone sections. Thus, it could be shown that both the
      collagen and the mineral crystals were predominantly aligned parallel to the
      trabeculae and, therefore, to principle stress directions. Moreover, the mean
      crystal thickness as determined by scanning SAXS was found to be different at
      various positions inside the trabecular and cortical structure. Finally, it could
      be shown that scanning SAXS is suitable for detecting local changes in bone
      material, e.g., due to fluoride treatment.

PMID- 10203417
TI  - Interleukin-1beta-induced release of matrix proteins into culture media causes
      inhibition of mineralization of nodules formed by periodontal ligament cells in
      vitro.
AB  - The mechanism by which interleukin-1beta (IL-1) inhibits the formation of
      mineralized tissue nodules by periodontal ligament (PDL) cells in vitro was
      investigated through the processes of morphological analysis,
      immunoprecipitation, and Northern blot analysis. PDL cells were obtained from a 2
      day-old coagulum in tooth socket and cultured in Dulbecco's Modified Eagle Medium
      (DMEM) containing 10% fetal bone serum (FBS) and antibiotics. Confluent cells
      were grown for up to 3 weeks in the presence of ascorbic acid (AA), beta
      glycerophosphate (GP), and dexamethasone (Dex), or IL-1. PDL cells cultured in
      the presence of GP and AA did not differentiate, but those treated with Dex, GP,
      and AA (Dex group) underwent differentiation, showing four stages (confluent,
      multilayer, nodule, and mineralization) of disparate morphological
      characteristics. In contrast, the cells treated with IL-1, Dex, GP, and AA (IL-1
      group) did form multilayers but failed to form mineralized nodules. Electron
      microscopy demonstrated that the Dex-induced mineralized nodules contain
      multilayers of fibroblastic cells, numerous collagen fibrils, and dense globular
      as well as fused electron dense patches that are associated with numerous apatite
      crystals. The nodule-like structures in the IL-1 group were also comprised of
      multilayered fibroblastic cells, but they contained only a small number of
      collagen fibrils, and no dense globular or fused patches. Von Kossa staining
      confirmed the presence of numerous mineralized nodules in the Dex group and their
      scarceness in the IL-1 group. Northern blot analysis of IL-1-treated cells,
      however, revealed the presence of mRNAs for type I collagen (Col I), secreted
      protein, acidic and rich in cysteine (SPARC), osteopontin (OPN), alkaline
      phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OC), whose
      expression patterns and levels were comparable to those of the Dex group.
      Immunoprecipitation analysis of OPN and BSP in the cell/matrix layers and the
      culture media after [35S]-methionine labeling showed their deposition primarily
      in the mineralized nodules of the Dex group, and their release into the media in
      the IL-1 group. Immunogold labeling demonstrated the location of OPN and BSP in
      mineralized nodules of the Dex group, but no significant labeling occurred in the
      nodule-like structures from the IL-1 group. Interestingly, IL-1 treatment
      increased the expression of collagenase mRNA by sevenfold, compared with that of
      the Dex group. These data suggest that the IL-1-induced formation of
      unmineralized nodules by PDL cells results not so much from the downregulated
      formation of matrix proteins, which plays a crucial role in the mineralization
      process, as from their release into the culture media. Finally, collagenase
      synthesis upregulated by IL-1 may be involved in this process.

PMID- 10203420
TI  - Ultrastructural study of apatite precipitation in implanted calcium phosphate
      ceramic: influence of the implantation site.
AB  - Macroporous biphasic calcium phosphate (MBCP) blocks were implanted into rabbit
      trabecular bone and muscle, recovered 18 weeks later, and then observed and
      analyzed by transmission electron microscopy (TEM), electron diffraction, and
      electron microprobes. The results showed that (1) apatitic microcrystals appeared
      by secondary nucleation in both bone and muscle sites; (2) precipitated
      microcrystals were aggregated around ceramic crystals in bone sites but
      distributed randomly and without orientation in micropores in muscle sites; (3)
      the ratio of calcium to phosphorus was higher for microcrystals in bone than
      muscle sites; and (4) precipitated microcrystals around beta-tricalcium phosphate
      (beta-TCP) crystals were less aggregated and dense than those around
      hydroxyapatite (HA). These findings suggest that microenvironmental parameters
      such as fluid circulation and the interaction of ceramics with proteins or cells
      affect the physicochemical dissolution/reprecipitation process. Epitaxic growth
      of apatitic microcrystals seems more favorable from HA than beta-TCP.

PMID- 10203421
TI  - Relationships among carbonated apatite solubility, crystallite size, and
      microstrain parameters.
AB  - The use of the metastable equilibrium solubility (MES) concept to describe the
      solubility properties of carbonated apatites (CAPs) and human dental enamel (HE)
      has been well established in previous studies using a range of CAPs with varying
      carbonate contents and crystallinities. It was shown in these studies that the
      mean value of the CAP MES is directly related to the broadening parameter full
      width at half maximum (FWHM) of the 002 reflection of the X-ray diffraction
      profile. The apparent solubility of the CAPs increased monotonically with an
      increase in the broadening of the diffraction peaks, and when this peak
      broadening was taken into account, carbonate had no additional effect upon the
      MES. The broadening of the diffraction peaks has been used as an indicator of
      crystallinity, and is generally influenced by both crystallite size and
      microstrain. The purpose of the present study was to extract the crystallite size
      and microstrain parameters separately from the X-ray diffraction peaks and then
      to determine their relationships to the corresponding MES values. The samples
      studied were CAPs synthesized by precipitation from Ca(NO3)2 and NaH2PO4
      solutions in carbonate containing media at temperatures of 95, 80, and 70 degrees
      C, and powdered HE. The crystallite size and microstrain parameters were
      determined simultaneously with the refinement of the structural parameters with
      the Rietveld method of whole-pattern-fitting structure-refinement. A modified
      pseudo-Voigt function was used to model the observed peak profiles. The MES
      distributions for the CAPs and HE were determined by a previously described
      method. The results of this study showed that the CAPs possessed an MES
      distribution and therefore provided further support that MES distribution is a
      common phenomenon, regardless of the method of CAP synthesis. The crystallite
      size decreased and the microstrain increased with increasing carbonate content
      and decreasing temperature of synthesis of the CAPs. A plot of the mean of the
      MES distribution versus the microstrain parameter showed that the apparent
      solubility of the CAPs and HE correlated very well with the microstrain
      parameter. On the other hand, a plot of the mean of the MES distribution versus
      the crystallite size parameter showed a poor correlation between MES and
      crystallite size. These findings support a view that microstrain, rather than
      crystallite size, is the dominant factor governing the effective solubility of
      the CAPs and dental enamel.

PMID- 10203422
TI  - Bone mass in the calcaneus after heavy loaded eccentric calf-muscle training in
      recreational athletes with chronic achilles tendinosis.
AB  - In an ongoing prospective study of 14 recreational athletes (12 males and 2
      females, mean age 44.2 +/- 7.1 years) with unilateral chronic Achilles
      tendinosis, we investigated the effect of treatment with heavy-loaded eccentric
      calf-muscle training. Pain during activity (recorded on a VAS scale) and
      isokinetic concentric and eccentric calf-muscle strength (peak torque at 90
      degrees /second and 225 degrees /second) on the injured and noninjured side were
      evaluated. In this group of patients, we examined areal bone mineral density
      (BMD) of the calcaneus after 9 months (range 6-14 months) of training. BMD of the
      injured side (subjected to heavy-loaded eccentric training) was compared with BMD
      of the noninjured side. Before onset of heavy-loaded eccentric training, all
      patients had Achilles tendon pain which prohibited running activity, and
      significantly lower concentric and eccentric plantar flexion peak torque on the
      injured compared with the noninjured side. The training program consisted of 12
      weeks of daily, heavy-loaded, eccentric calf-muscle training; thereafter the
      training was continued for 2-3 days/week. The clinical results were excellent-all
      14 patients were back at their preinjury level with full running activity at the
      3 month follow-up. The concentric and eccentric plantar flexion peak torque had
      increased significantly and did not significantly differ from the noninjured side
      at the 3 and 9 month follow-up. There were no significant side-to-side
      differences in BMD of the calcaneus. There was no significant relationship
      between BMD of the calcaneus and calf-muscle strength. As a comparison group, we
      used 10 recreational athletes (5 males and 5 females) mean age 40.9 years (range
      26-55 years), who were selected for surgical treatment of chronic Achilles
      tendinosis localized at the 2-6 cm level. Their duration of symptoms and severity
      of disease were the same as in the experimental group. There were no significant
      side-to-side differences in BMD of the calcaneus preoperatively, but 12 months
      postoperatively BMD of the calcaneus was 16.4% lower at the injured side compared
      with the noninjured side. Heavy-loaded eccentric calf-muscle training resulted in
      a fast recovery in all patients, equaled the side-to-side differences in muscle
      strength, and was not associated with side-to-side differences in BMD of the
      calcaneus. In this group of middle-aged recreational athletes, BMD of the
      calcaneus was not related to calf-muscle strength.

PMID- 10203423
TI  - Familial hypocalciuric hypercalcaemia in Australia.

PMID- 10203424
TI  - An update and a revisit.

PMID- 10203425
TI  - Burning issues. A guide for patients. Lactose intolerance.

PMID- 10203427
TI  - Gene-targeted fulminant jejuno-ileitis in mice

PMID- 10203428
TI  - What is the impact of the use of nonsteroidal anti-inflammatory drugs?

PMID- 10203426
TI  - Soothing the irritable bowel syndrome.

PMID- 10203429
TI  - The epidemiology of nonsteroidal anti-inflammatory drugs.
AB  - Nonsteroidal anti-inflammatory drug (NSAID) use has increased dramatically in the
      past two decades. A large proportion of the elderly population (more than 65
      years of age) holds a current or recent NSAID prescription, accounting for
      approximately 90% of all NSAID prescriptions. Despite studies that advise finding
      alternatives for NSAIDs for the management of osteoarthritis, physicians often
      prescribe NSAIDs first for such common musculoskeletal conditions. Despite being
      identified as risk factors for gastrointestinal complications, the simultaneous
      use of two NSAIDs and the coadministration of NSAIDs with corticosteroids and
      with coumadin continue to occur. The point prevalence of NSAID-induced ulcers is
      10% to 30%, and 15% to 35% of all peptic ulcer complications are caused by
      NSAIDs. The increased risk of gastrointestinal complications when NSAIDs are used
      is 3% to 5%. This risk increases with other identified risk factors (eg, older
      age, previous gastrointestinal history, comorbid diseases and poor health).
      Gastrointestinal causes of hospitalization (eg, gastrointestinal hemorrhage and
      perforation) and death have increased in parallel to increased NSAID use.
      'Antiulcer' agents are prescribed twice as often in NSAID users, and the economic
      impact (eg, diagnostic tests and hospitalization) is that about one-third of the
      arthritis budget has been dedicated to deal with gastrointestinal side effects of
      NSAIDs. Misoprostol and omeprazole have been shown to be cytoprotective for the
      gastroduodenal mucosa when NSAIDs are used, and misoprostol has been shown to
      reduce the risk of gastroduodenal ulcer complications. Economic evaluations have
      suggested that these agents are a cost effective means of dealing with such NSAID
      associated problems. Although no NSAID is totally safe, a number of studies have
      demonstrated that NSAIDs may be ranked according to relative gastrointestinal
      toxicity. The role of Helicobacter pylori in NSAID-associated problems remains
      uncertain.

PMID- 10203430
TI  - Pathogenesis of nonsteroidal anti-inflammatory drug gastropathy: clues to
      preventative therapy.
AB  - Gastric ulceration and bleeding are major impediments to the chronic use of
      nonsteroidal anti-inflammatory drugs (NSAIDs). The development of effective
      therapies for prevention of these adverse effects requires better understanding
      of their pathogenesis. Several features of NSAIDs contribute to the development
      of damage in the stomach, including the topical irritant effects of these drugs
      on the epithelium, impairment of the barrier properties of the mucosa,
      suppression of gastric prostaglandin synthesis, reduction of gastric mucosal
      blood flow and interference with the repair of superficial injury. The presence
      of acid in the lumen of the stomach also contributes to the pathogenesis of NSAID
      induced ulcers and bleeding in a number of ways. Acid impairs the restitution
      process, interferes with hemostasis and can inactivate several growth factors
      that are important in mucosal integrity and repair. Profound suppression of
      gastric acid secretion has been shown to be effective in preventing NSAID-induced
      ulceration. There is a strong possibility that new NSAIDs entering the market
      will have greatly reduced toxicity in the gastrointestinal tract.

PMID- 10203431
TI  - Quality of life in arthritis patients using nonsteroidal anti-inflammatory drugs.
AB  - Arthritis is a painful and disabling condition. To suppress the pain and the
      inflammatory process, patients are often chronic nonsteroidal anti-inflammatory
      drug (NSAID) users. Chronic use of NSAIDs may induce peptic ulcer, dyspeptic
      problems and heartburn. Therefore, these patients are often provided with
      treatment to relieve and/or protect against gastrointestinal problems. Rheumatic
      disorders also affect a range of health-related quality of life domains. In one
      study, patients with NSAID-associated gastroduodenal lesions complained about
      lack of energy, sleep disturbances, emotional distress and social isolation in
      addition to pain and mobility limitations. The degree of distress and dysfunction
      differed markedly from scores in an unselected population. Clinical trial data
      suggest that acid-suppressing therapy with omeprazole is superior to therapy with
      misoprostol and ranitidine in healing gastroduodenal lesions and preventing
      abdominal pain, heartburn and indigestion symptoms during continued NSAID
      treatment. Because arthritic patients are severely incapacitated by their
      condition regarding most aspects of health-related quality of life, it is
      important to offer a treatment that is effective in healing and preventing NSAID
      induced ulcers and gastrointestinal symptoms during continued NSAID treatment
      without further compromising the patients' quality of life. Treatment with
      omeprazole once daily has been shown to be superior to that with ranitidine and
      misoprostol in this respect.

PMID- 10203432
TI  - Management of nonsteroidal anti-inflammatory drug-induced gastroduodenal disease
      by acid suppression.
AB  - One major cause of peptic ulceration is the use of nonsteroidal anti-inflammatory
      drugs (NSAIDs). The precise mechanisms through which NSAIDs cause peptic
      ulceration are unknown, but the discovery that they reduce the production of
      'cytoprotective' prostaglandins led to the hypothesis that coadministration of
      exogenous prostaglandins heals and prevents NSAID-induced gastroduodenal ulcers
      and other mucosal lesions. Studies using high doses of misoprostol have shown
      that it does have a protective effect; however, gastrointestinal intolerance of
      this prostaglandin E2 analogue is common. Early indications that acid suppression
      was effective in the management of NSAID-related peptic ulcers came from studies
      showing that gastric ulcers could be healed by omeprazole in patients who
      continued to take NSAIDs. Other studies suggested that acid suppression reduces
      the incidence of mucosal lesions but that standard dose ranitidine protects only
      against duodenal lesions. Subsequent studies reported that higher dose H2
      receptor antagonist therapy can protect against both gastric and duodenal ulcers
      during continued NSAID therapy. An ideal therapeutic strategy would heal NSAID
      related ulcers and prevent the development of new NSAID-related lesions and
      complications in patients who are unable to discontinue NSAID therapy. A number
      of recent studies indicate that effective acid-suppressive treatment with the
      proton pump inhibitor omeprazole can achieve these aims. Overall, data from
      recent studies show that acid suppression with the proton pump inhibitor
      omeprazole at a dose of 20 mg daily is the most effective means of healing NSAID
      associated gastroduodenal lesions and that it is the most effective prophylactic
      therapy. In the long run, the role of omeprazole will have to be evaluated with
      respect to its cost effectiveness compared with other strategies and with respect
      to the development of less damaging NSAIDs.

PMID- 10203433
TI  - What do we do about Helicobacter pylori?
AB  - Heliobacter pylori and nonsteroidal anti-inflammatory drugs (NSAIDs) cause ulcers
      by different mechanisms. Under some circumstances, patients infected with H
      pylori may be less prone to NSAID-associated ulcers than those who are H pylori
      negative. Eradication trials have yielded differing results. However, those who
      have studied patients who have a past history of ulcer disease and are already
      established on NSAIDs have shown no benefit from H pylori eradication.

PMID- 10203434
TI  - Changing parenteral nutrition administration sets every 24 h versus every 48 h in
      newborn infants.
AB  - OBJECTIVE: To determine whether changing total parenteral nutrition fluid
      administration sets (TAS) every 48 h rather than every 24 h results in a greater
      infusate contamination rate. PATIENTS AND METHODS: Prospectively, 166 infants
      were assigned at random to have TAS changed either every 24 h or every 48 h.
      Samples of the infusate were cultured to determine contamination rates of the
      infusate in the sets and were tested from 149 of these infants. TAS was replaced
      every 24 h in the control group, and 445 amino acid plus dextrose solutions
      (AADS) and 449 lipid emulsions samples were taken for bacterial culture. Fungal
      cultures were also performed on 449 samples. The study group had TAS replaced
      every 48 h, and 454 samples of AADS were cultured for bacteria. The numbers of
      lipid emulsion samples sent for bacterial culture and fungal culture were 449 and
      440, respectively. Information on type of intravenous access device,
      administration of antibiotics and blood cultures was also collected. RESULTS:
      There was no difference in bacterial contamination rates for AADS or lipid
      emulsion from TAS changed every 24 or 48 h (c2, P>0.05). Lipid emulsion sampled
      from the 24 h group showed a statistically significant higher rate of fungal
      contamination than specimens from the 48 h group (P<0.01). CONCLUSIONS: Changing
      TAS every 48 h versus 24 h does not increase the contamination rate of infusate
      in newborns.

PMID- 10203435
TI  - Crohn's disease and the Melkersson-Rosenthal syndrome.
AB  - A 30-year-old woman with a 10-year history of recurrent bloody diarrhea and
      documented colitis of the descending colon, consistent with Crohn's disease,
      presented with an exacerbation of her gastrointestinal disease and an 18-month
      history of recurrent facial and genital swelling. Her course evolved to include
      severe ear pain, dysphagia and colonic dysmotility. She was diagnosed with
      Melkersson-Rosenthal syndrome and treated with multiple agents. The neurological
      aspects of her presentation are highlighted, and the Melkersson-Rosenthal
      syndrome is reviewed.

PMID- 10203436
TI  - Acute pseudohepatitis in a chronic substance abuser secondary to occult seat belt
      injury.
AB  - Causes of a massive elevation in serum aminotransferases (aspartate
      aminotransferase [AST] and alanine aminotransferase [ALT]) in the substance
      abusing patient include viral hepatitis and drug hepatotoxicity. A patient
      chronically addicted to injection heroin and cocaine presented to the emergency
      room in a confused state and was admitted to a medical ward with an AST of 4120
      U/L, ALT 3820 U/L and right upper quadrant discomfort. Investigations for viral
      and hepatotoxic causes for the liver dysfunction revealed only hepatitis C
      seropositivity. A computed tomogram of the abdomen, however, revealed a
      significant contusion to the right lobe of the liver consistent with traumatic
      injury. A motor vehicle accident, in which the patient was wearing a seat belt,
      and which had occurred a few days before admission and had been thought to be
      minor, was the cause of the liver dysfunction. Significant blunt abdominal
      traumatic injuries are usually managed exclusively by surgical trauma units. This
      case underlines the need for medical specialists to be aware of hepatic contusion
      injuries and to have a high index of suspicion when investigating unexplained
      hepatocellular dysfunction in chronic substance abusers who have been in motor
      vehicle accidents.

PMID- 10203437
TI  - Lupus-like syndrome caused by 5-aminosalicylic acid in patients with inflammatory
      bowel disease.
AB  - BACKGROUND: Although 5-aminosalicylic acid (5-ASA) preparations used to treat
      inflammatory bowel disease are reported to have fewer side effects than
      sulphasalazine, increased clinical use of these compounds has resulted in
      increased reports of significant side effects. OBJECTIVE: To report four patients
      with antinuclear antibody-positive migratory arthralgias and acute inflammation
      unrelated to the underlying inflammatory bowel disease, fulfilling the criteria
      of a drug-induced lupus-like syndrome. SETTING: A university-affiliated teaching
      hospital. INTERVENTION: Cessation of treatment with 5-ASA compounds. RESULTS: The
      cases described constitute a drug-induced lupus-like syndrome. All patients
      improved rapidly after discontinuation of 5-ASA compounds. CONCLUSIONS:
      Reversible lupus-like syndrome appears to be a rare but significant side effect
      of 5-ASA compounds. Patients treated with 5-ASA compounds who experience acute
      inflammatory symptoms or clinical deterioration not related to their
      gastrointestinal disease should be screened to rule out a lupus-like reaction.

PMID- 10203439
TI  - The 'true' splenic wanderer.
AB  - Wandering spleen is an unusual entity and remains an elusive clinical diagnosis.
      Among the modern imaging modalities including computed tomography, magnetic
      resonance imaging, nuclear scans and ultrasonography, the latter appears to be
      the least invasive and the most effective in reaching a definitive diagnosis. A
      patient with 'true' wandering spleen who presented with chronic, intermittent
      abdominal pain, weight loss and a right lower quadrant mass that was interpreted
      as a pelvic lymphoma or a primary pelvic malignancy on computed abdominal
      tomography (CAT) scan is presented. Abdominal ultrasonography conducted a few
      weeks before the CAT scan showed a normal splenic shadow in the left upper
      abdomen.

PMID- 10203438
TI  - Rhabdomyolysis complicating unrecognized hypophosphatemia in an alcoholic
      patient.
AB  - Rhabdomyolysis occurring as a complication of hypophosphatemia has been
      infrequently described. A 58-year-old male with a history of daily alcohol
      consumption presented with two generalized tonic clonic seizures secondary to
      hypovolemic hyponatremia. He was volume-resuscitated, and antiepileptic
      medication was administered. After three days of hospitalization, the patient
      developed severe rhabdomyolysis despite the absence of further seizure activity.
      Serum phosphate levels were depressed. He was treated with intravenous mannitol,
      alkaline diuresis, and intravenous and oral phosphate supplementation. He
      recovered uneventfully. Hypophosphatemia can potentially lead to multisystem
      organ dysfunction including severe rhabdomyolysis. It is, therefore, important to
      maintain a low threshold for measuring serum phosphate levels in patients
      admitted to hospital.

PMID- 10203440
TI  - Canadian gastroenterologists: workforce data in urgent need.

PMID- 10203441
TI  - Science and collective health: on the need for critical reason.

PMID- 10203442
TI  - Attitudes towards Chagas' disease in an endemic Brazilian community.
AB  - Chagas' disease remains a major public health concern throughout much of Latin
      America. In Brazil, segments of the population experience Trypanosoma cruzi
      infection rates as high as 65%, indicating that control programs are still
      needed. Few data are available concerning people's health beliefs related to
      Chagas' disease in heavily infected populations. Such health beliefs may
      significantly impact the effectiveness of intervention schemes. The purpose of
      this study was to assess health beliefs related to Chagas' disease in a
      population experiencing infection high rates with the causal parasite. The focal
      population for the study consisted of the residents of Posse, a rural community
      in the State of Goias. The results indicate that a majority of the population had
      a high degree of knowledge about Chagas' disease and the vector involved in its
      transmission. These findings indicate that control programs conducted by the
      Brazilian Ministry of Health have included effective educational components.

PMID- 10203443
TI  - [Income inequality and health: the case of Rio de Janeiro].
AB  - This ecological analysis addresses the association between income inequality and
      health status in the municipality of Rio de Janeiro. Data were analyzed using geo
      processing and multiple regression techniques. The following health indicators
      were used: infant mortality rate; standardized mortality rate; life expectancy at
      birth; and homicide rate among 15-29-year-old males. Patterns of income
      inequality were assessed through income distribution indicators: Gini index,
      Robin Hood index, and top 10 %/bottom 40% average income ratio. The results
      indicate significant correlations between income distribution indicators and
      health indicators, providing additional empirical evidence of the association
      between health status and income inequality. For the homicide rate, the effect of
      the indicator "density of slum residents" was also relevant, suggesting that
      further deterioration in health standards may be due to social disruption of
      deprived communities and the resultant increase in criminal activity. The geo
      epidemiological analysis presented here highlights the association between
      adverse health outcomes and residential concentration of poverty. Social policies
      focused on slum residents are needed to reduce the harmful effects of relative
      deprivation.

PMID- 10203445
TI  - [Restructuring of production and occupational accidents in Brazil: structure and
      trends].
AB  - During the last two decades, incidence rates of occupational accidents have been
      decreasing in Brazil. Mortality has also decreased, but not as sharply as
      incidence. Changes in reporting of occupational accidents have been the main
      argument used to explain such trends. This time-series study covering
      occupational accidents from 1970 to 1995 clearly shows the link between
      occupational accidents and social and economical determinants. Comparing 14
      Brazilian States, a positive linear regression (r=0.80) was detected between
      proportion of workers in industrial production and accidents. In the 1980s,
      Brazil's economic recession led to an increase in unemployment. The decline in
      industrial jobs - those with a higher risk of accidents ( was accented by the
      restructuring of production and increased use of computer and robotics
      technologies in various manufacturing sectors. The result was a heavy shift of
      the work force from industry to commerce and services - jobs entailing lower risk
      of accidents. These factors influenced trends in occupational accidents in Brazil
      during this 25-year period.

PMID- 10203444
TI  - [Eating habits among employees of a state-owned bank: food consumption profile].
AB  - In order to investigate the health conditions of current employees in a
      government-owned bank in the State of Rio de Janeiro, we performed a cross
      sectional study in two departments where systematic sampling was applied. Among
      the health conditions, we focused on the employees' eating habit profile using a
      questionnaire on frequency of food group consumption analyzed through a summary
      measure (eating score). Although the majority of the study population display
      good eating habits, the results confirmed a major difference between genders.
      Some 60% of men had scores higher than the population mean (51.2), as compared to
      only 45% of women. In addition, we observed that men, and particularly younger
      men, consumed more foodstuffs that were rich in saturated fat, salt, and sugar as
      compared to women. The findings indicate that quality of one's diet along with
      changes in other habits and behaviors (like smoking and sedentary life style)
      should be part of programs to promote health in the workplace, with a view
      towards controlling cardiovascular and other diseases.

PMID- 10203446
TI  - [Surveillance of endemic diseases in urban areas: the interface between census
      tract maps and morbidity data].
AB  - In this article we discuss the methodological issues associated with the creation
      of a surveillance system for endemic diseases in urban areas based on analysis of
      populations at risk and on spatially referenced epidemiological indicators. We
      comment on the system's basic requirements, selection criteria for socioeconomic
      variables, and methodological steps to combine these variables so as to construct
      a census-based deprivation index. We also present the ways we solved some
      operational problems related to generation of digitized census tracts maps and
      linkage of morbidity data from different sources. This approach, spatial
      organization into account in surveillance of endemic diseases, exemplified here
      by tuberculosis and leprosy, allows for the interaction of several official data
      sets from census and health services in order to geographically discriminate
      inner-city risk strata. Criteria for constructing these risk strata were
      considered a useful tool for health planning and management activities for the
      control of endemic diseases in cities.

PMID- 10203447
TI  - Association between diastolic blood pressure and cumulative work time.
AB  - Diastolic blood pressure was viewed as a generic indicator of aging, and its
      association with cumulative work time was studied after controlling for age as a
      potential confounding factor. The study was conducted among production line
      workers at a Brazilian tannery in July 1993. The association between diastolic
      blood pressure and cumulative work time was verified by fitting a second-order
      linear regression model, where diastolic blood pressure was a function of
      worker's age and cumulative work time. By fitting the model, one can predict
      that, from the beginning of working life at the tannery, on average each 1-year
      period is associated with an increase of about 1. 5 mmHg in diastolic blood
      pressure. The fit obtained highlights a component directly associated with work
      as part of the rate of pressure increase in the study group. This component is
      twice as high as that directly associated with age.

PMID- 10203448
TI  - [Nutritional status of social groups in greater metropolitan Sao Paulo, Brazil].
AB  - This paper focuses on prevalence of nutritional status (Body Mass Index, BMI) in
      social groups in greater metropolitan Sao Paulo, in Southeastern Brazil. The
      population was stratified in four socioeconomic groups. Prevalence of
      malnutrition (BMI<18.5kg/m2), low body mass (BMI<20.0kg/m2), and overweight
      (BMI>25.0kg/m2) and obesity (BMI(30.0kg/m2) were calculated. Prevalence of
      malnutrition was 3.9% in men and 6.2% in women. Prevalence of overweight ranged
      from 27.5% to 34.1% in men and from 25.8% to 43.6% in women. Obesity ranged from
      2.5% to 11.1% in men and from 7.1% to 20.5 in women. Prevalence of overweight and
      obesity was greater among women than men (p<0.01). In relation to excess weight
      (BMI>25.0kgm/2), the study showed that prevalence in men was 43, 51, 35, and 30%
      for strata I, II, III, and IV, respectively. Among women, prevalence was 12, 61,
      55 and 46% for strata I, II, III, and IV, respectively. In women there were an
      abrupt increase in excess weight just before 40 years of age. A high percentage
      of overweight and obesity was observed in all population groups.

PMID- 10203449
TI  - [Challenges for developing a comparative analytical model for health services].
AB  - This paper presents different models that describe health determinants, services,
      and systems. It highlights the important model developed by Contandriopoulos,
      proposing a separation between the health status and health care circuits. The
      article is intended as a contribution to the field of comparative analysis with a
      new theoretical, methodological, and evaluative approach. Problems were
      identified in the development of a new model. Decentralization and access are
      introduced as categories, suggesting that they may take part in such new model.

PMID- 10203450
TI  - [Depression during pregnancy and preterm delivery. Epistemological aspects in
      research].
AB  - This paper examines recent research on the association between depression during
      pregnancy and preterm delivery. Dissemination of scientific information on this
      disease entity (depression) means that it is often present in common-sense
      discourse, although frequently used rather imprecisely. While various areas from
      the mental health field approach depression in very different ways, they suggest
      the influence of emotional states on organic outcomes. Still, this relationship
      remains difficult to prove by conventional scientific research methods. One
      problem in establishing associations between depression and preterm delivery
      appears to be due to epistemological aspects related to the theoretical
      demarcation of depression.

PMID- 10203451
TI  - [Thalidomide in Brazil: monitoring with shared responsibility?].
AB  - This paper discusses issues related to the regulation and rational use of
      thalidomide in Brazil, by means of a historical approach comprising three
      different stages. The first part is a historical review of the controversial drug
      since it was first synthesized, then marketed and subsequently banned during the
      1950s and 60s, until the present, when an apparently irreversible process of
      rehabilitating the drug is under way. Brazilian experience with the use of
      thalidomide is described, emphasizing legal, political, and institutional work
      led by two social movements, the Brazilian Association of People with Thalidomide
      Syndrome (ABPST) and the Movement for Reintegration of People with Hansen's
      Disease (Morhan). The article describes the results and analyzes an active search
      of new cases in what is a second generation of thalidomide syndrome in Brazil.
      Finally, based on clinical and scientific evidence of thalidomide's therapeutic
      efficacy, the growth of social movements struggling both for and against
      authorization of the drug, and a restrictive regulation proposed by the Ministry
      of Health, the article discusses the implementation of policies for the
      regulation and rational use of thalidomide in Brazil.

PMID- 10203452
TI  - [Anthropometric profile of employees from a government bank in the state of Rio
      de Janeiro, Brazil. 1 Body mass index and sociodemographic factors].
AB  - This study first describes the anthropometric profile of employees at Banco do
      Brasil and then compares these results to those of the Brazilian National Health
      and Nutritional Survey, PNSN/1989, for the Southeastern region of the country. It
      is a cross-sectional study with a sample comprising 647 bank clerks. Weight and
      height informed by respondents were used to compute the body mass index (BMI).
      Among bank clerks, 8.8% were underweight, 27.8% were overweight and 6.4% were
      obese. Overweight increased with age and was about 3 times greater in men than in
      women. Among social and demographic variables, sex, age, and schooling best
      explained BMI variance. For men, proportion of overweight was higher in bank
      clerks than in the PNSN population, while for women, PNSN showed higher
      frequencies of overweight as compared to female bank clerks. High prevalence of
      overweight in the general population, as well as in specific groups like bank
      clerks, highlights the urgent need for definition and development of prevention
      and control policies capable of impacting risk factors and ultimately leading to
      a decrease in social cost due to mortality from chronic diseases.

PMID- 10203453
TI  - [Occupational lead exposure assessment: a proposal for a strategy to monitor
      prevention of clinical and subclinical effects].
AB  - In developing countries, lead-acid battery factories are one of the heaviest
      consumers of lead. Due to lead's toxicological properties and prevalent working
      conditions in such factories, workers are subject to high exposure and health
      risk. This study discusses results obtained by lead exposure assessment of
      workers from a Rio de Janeiro battery factory, in light of Brazilian legislation
      and recent scientific data. Evaluation methods used were environmental (personal
      air sampling) and biological (determination of lead in blood, Pb-B) monitoring,
      showing a high personal exposure both in air (>0.1 mg/m3) and blood (55% of Pb-B
      >25 microg/dl). These results confirmed the inefficiency of current control
      measures, with a possible 46% of workers presenting a Pb-B range of 25-60
      microg/dl in risk areas. Recent data suggest that Pb-B levels above 25 microg/dl
      are related to subclinical alterations in human body that should be investigated
      during clinical examination. Finally, we propose a strategy based on
      environmental and biological monitoring to prevent both clinical and subclinical
      effects.

PMID- 10203454
TI  - [Between merit and need: an analysis of the underlying principles in social
      health insurance in Germany].
AB  - This article describes and analyzes the structural principles of social health
      insurance in Germany and discusses their interrelations and current form.
      Focusing on salaried work, social security in Germany links rights and duties to
      the place occupied by workers in the production process and maintains a
      differentiation in their status. As a paradigm of social security, citizens'
      social rights in Germany are organized according to principles of equivalence,
      subsidiarity, and solidarity. The coexistence of these contradictory principles
      generates a constant field of tension and conditions their effect, thus mediating
      how each one is implemented. This tension, which has always existed in the
      underlying system, is reedited each time the political context changes. While
      subsidiarity and equivalence prevailed in the original social security system,
      the solution to the conflict tended towards solidarity during the expansion of
      welfare states and social health insurance. At present, however, there is a call
      for reediting subsidiarity and equivalence.

PMID- 10203455
TI  - [New technologies and workers' health: mechanization of sugar cane harvesting].
AB  - In the context of reorganization of production in the sugar and alcohol industry,
      mechanization of sugar cane harvesting has been justified as a protective measure
      for the environment and workers. This article focuses on the consequences of
      organization of work in mechanization of sugar cane harvesting with regard to the
      harvester operators' health. Based on data gathered through interviews and direct
      observation at the workplace, changes implemented in the technological base and
      division of labor and organization were analyzed, identifying the work load
      inherent to the process and how it affects workers' health. While harvesters help
      decrease the physical, chemical, and mechanical work load, they increase the
      physiological and psychological work load. There is evidence of significant
      change in the pattern of work-related accidents, entailing a decrease in their
      frequency and increase in severity. The pattern of illness among harvester
      operators is similar to that of manual sugar cane cutters, with a highlight on
      psychosomatic illness related to the organization of work in shifts and increased
      tempo due to use of machinery.

PMID- 10203456
TI  - [Incidence and risk factors for diarrhoea and acute respiratory infections in
      urban communities of Pernambuco, Brazil].
AB  - Magnitude and distribution of Diarrhoea and Acute Respiratory Infections (ARI) in
      children were studied within a larger broader research that focused on health
      education. Two household surveys were conducted in a sample of families with at
      least one child under five years of Recife and Olinda in April-May 1992 and 1994.
      The total number of children studied was 5,436. The estimated adjusted annual
      incidence rate (AAIR) of diarrhoea was 2.7 episodes per child. The two-week
      incidence rate of diarrhoea was 10.2% for both years. Risk factors associated
      with higher incidence of diarrhoea were age (under two years), lack of sanitation
      facilities, and absence of electrical appliances in the household. Estimated AAIR
      of ARI was 9. 5 episodes per child. The two-week incidence rate of ARI was 41.0%
      in 1992 and 32.6% in 1994. Majority of ARIs affected the upper respiratory tract
      (75.9%). The only factor consistently associated with a higher risk of ARI was
      age (under three years). Study results indicate that both pathologies are still
      an important health problem for children under five in Pernambuco. In particular,
      in the case of diarrhoea the need for improving the access to basic services,
      such as water supply and sewage system is urgently needed.

PMID- 10203457
TI  - [Ascaris lumbricoides in infants: a population-based study in Rio de Janeiro,
      Brasil].
AB  - Prevalence and intensity of Ascaris lumbricoides infection were analyzed by a
      cross-sectional study in children addressed in the city of Duque de Caxias, Rio
      de Janeiro State, from July to December 1997. The study population consisted of
      children under two years of age (N=387) and mothers of children under one year of
      age (N=104). Coproparasitologic tests were run using the MIFC and the Kato thick
      smear (Kato-Katz) methods. Prevalence was 3.3% (95% CI: 1.0-7.8) for children
      under one year, 30.7% (95% CI: 25.4-36.4) for one-year-olds, and 42.3% (95% CI:
      33.0-51.9) for mothers of children under one. Some 38.0% of children under one
      year of age showed medium-to-heavy infection. These results indicated that
      ascariasis was an important problem in the first year of life and demonstrated
      the need for research in the area of maternal and infantile ascariasis.

PMID- 10203458
TI  - [The patient's perspective. Reflections on past, present, and future in the
      chronic illness experience].
AB  - The illness experience is a relevant issue in current research and academic
      discussions. A growing number of research initiatives have undertaken to account
      for the subject's perspective and subjectivity in the health field. This paper
      discusses our research team's approach and results in studying the experience of
      people living with chronic illness. Our perspective is based upon the production
      in this relatively new field as well as health-related discussions in Latin
      America. The illness experience calls for an understanding of it as a subjective
      and existential phenomenon, entailing the phenomenological arena, immersed in the
      process where ill people "produce" and "reproduce" themselves. The unfolding and
      course of the illness as well as treatment management are some salient dimensions
      we evoke. Some lines of future work are presented in order to create a research
      agenda, highlighting its implications for existing proposals pertaining to health
      reform in our Latin American countries.

PMID- 10203459
TI  - [Physician training, university hospitals, and the Unified Health System in
      Brazil].
AB  - There are 80 medical schools in Brazil, of which 14 were selected for this study
      based on their regional distribution and representative characteristics. A survey
      in 1995 showed a heavy concentration (86%) of in-house practical training in
      major university hospitals. Only 14% of the hands-on training of students
      occurred in primary health or community-based clinics or other services related
      to the nationwide Unified Health System (SUS). University hospitals have been
      organized according to the specialized ward model, with extensive fragmentation
      of health care. This article makes several proposals for improving medical
      training. Changes in medical care are considered crucial to improvement of
      physician training. Reforms in medical care in such hospitals would be more
      important than reformulating the medical school itself. A move towards other
      health care services is recommended; more time devoted to teaching in primary
      health care systems and other extramural services is crucial for achieving better
      physician responsibility and competence.

PMID- 10203461
TI  - [The development of pharmacoepidemiology in Brazil: I Brazilian seminar on
      pharmacoepidemiology].

PMID- 10203460
TI  - [Views on the municipalization of lymphatic filariasis control in greater
      metropolitan Recife].
AB  - Lymphatic filariasis is caused by the nematodes Brugia malayi, Brugia timori, and
      Wuchereria bancrofti. The disease occurs in developing countries and is more
      frequent in urban areas. An estimated 4 billion people live in at-risk areas. In
      Brazil the endemic is caused by W. bancrofti and was first documented in 1878. It
      was first detected in Recife in 1952. Currently, Recife and Belem are the only
      cities in Brazil where the endemic is considered a public health problem. The
      objectives of this study are to discuss the epidemiology and control of lymphatic
      filariasis and review its control since it was reported by Rachou in 1952. We
      analyze the "campanhista" or campaign-oriented model employed by the Sucam/FNS
      institutional program, as well as several proposed innovative methods. We present
      available strategies for control of filariasis through primary health care
      services, decentralization to the local level (or "municipalization"), and
      community-based health programs.

PMID- 10203463
TI  - Clinical microbiology and ASM: quo vadis? American Society for Microbiology.

PMID- 10203462
TI  - [Pharmacovigilance in Brazil. The role of the commission established under ruling
      No. 40 (May 9, 1995) of the Health Surveillance Secretariat, Brazilian Ministry
      of Health].

PMID- 10203464
TI  - Evaluation of three glycoprotein G2-based enzyme immunoassays for detection of
      antibodies to herpes simplex virus type 2 in human sera.
AB  - Three new glycoprotein G-based enzyme immunoassays (ETI-HSVK-G 2, Sorin
      Diagnostics Biomedica [assay A]; HSV Type 2 Specific IgG ELISA, Gull
      Laboratories, Inc. [assay B]; Cobas Core HSV-2 IgG EIA, Roche [assay C]) for the
      detection of herpes simplex virus (HSV) type 2 (HSV-2)-specific antibodies were
      evaluated. By testing sera from 25 individuals with culture-proven HSV-2
      infection, the assays showed a sensitivity of 96%. The specificities, evaluated
      with sera from 70 HSV antibody-negative children, 75 HSV antibody-positive
      children, and 69 HSV antibody-negative adults, were 100% for assay A, 96.2% for
      assay B, and 97.8% for assay C, respectively. Discrepant results by any of the
      three assays, i.e., reactivity of a specimen in only one or two assays, occurred
      with similar frequencies for HSV-seronegative individuals as well as HSV
      seropositive children and adults. For sera with discrepant results, the positive
      reactivity was mostly low. Thus, for determination of the prevalence of HSV-2
      antibodies, only concordantly positive results were considered. On the basis of
      the results obtained with sera from 41 adults with culture-proven HSV-1 infection
      and from 173 HSV-antibody-positive pregnant women, the HSV-2 seroprevalence was
      9. 8%. The results show that the new glycoprotein G2-based enzyme immunoassays
      are useful tools for the detection of type-specific HSV-2 antibodies. However, if
      only one assay is performed, careful interpretation of the results is indicated,
      especially if the exhibited reactivity is low, and for determination of the
      definitive HSV-2 serostatus, confirmatory assays may still be necessary.

PMID- 10203465
TI  - Studies of genetic relationships between bovine, caprine, cervine, and
      rangiferine alphaherpesviruses and improved molecular methods for virus detection
      and identification.
AB  - The glycoprotein B (gB) and D (gD) genes from five ruminant alphaherpesviruses,
      bovine herpesvirus 1 (BHV-1), bovine herpesvirus 5 (BHV-5), caprine herpesvirus 1
      (CapHV-1), cervine herpesvirus 1, and rangiferine herpesvirus 1, were partially
      sequenced. The nucleotide sequence alignments revealed a highly conserved gB
      gene, with homologies ranging between 87.2 and 99.6%, and a more variable gD
      gene, with homologies ranging between 71.3 and 98.9%. The phylogenetic analysis
      of the gB and gD nucleotide and deduced amino acid sequences revealed that BHV-5
      is the most closely related virus to the BHV-1 subtype 1 and BHV-1 subtype 2
      cluster and that CapHV-1 is the most distantly related virus. The phylogenetic
      data showed a close relationship of all the studied viruses with suid herpesvirus
      1. On the basis of sequence data for the gB gene, a nested PCR combined with
      restriction enzyme analysis (REA) of the PCR products was developed for the
      simultaneous detection and identification of the viruses that were studied.
      Nested primers from highly conserved sequence stretches were selected in order to
      amplify a region of 294 bp in all five viruses, and a subsequent REA of the PCR
      products allowed specific identification. A mimic molecule that served as an
      internal standard of the amplification efficiency was constructed. The practical
      diagnostic applicability of the assay was evaluated with clinical samples
      consisting of semen and organ specimens from experimentally infected animals.

PMID- 10203466
TI  - Prevalence of Mycobacterium avium in slaughter pigs in The Netherlands and
      comparison of IS1245 restriction fragment length polymorphism patterns of porcine
      and human isolates.
AB  - A significant increase in the incidence of caseous lesions in the lymph nodes of
      slaughter pigs prompted a large-scale investigation in five slaughterhouses in
      The Netherlands. In total, 158,763 pigs from 2,899 groups underwent gross
      examination. At least one pig with caseous lesions in the submaxillary and/or
      mesenteric lymph nodes was observed in each of 154 of the 2,899 groups examined
      (5%). In total, 856 pigs (0.5%) were affected. As many as five pigs in each of
      141 of the 154 positive groups (91.5%) had lymph node lesions. Greater numbers of
      pigs with affected lymph nodes were found in 13 groups (8.5%). Four pigs had
      lesions in the kidneys, liver, or spleen. Acid-fast bacteria were detected by
      microscopic examination of 121 of 292 Ziehl-Neelsen-stained smears of caseous
      lesions (41%). In a follow-up study, Mycobacterium avium complex (MAC) bacteria
      were isolated from 219 of 402 affected lymph nodes (54.2%). Ninety-one of the
      isolated strains were analyzed by restriction fragment length polymorphism (RFLP)
      typing with insertion sequence IS1245 as a probe. All but 1 of these 91 strains
      contained IS1245 DNA, indicating that pigs in The Netherlands carried almost
      exclusively M. avium bacteria and no other bacteria of MAC. Only one pig isolate
      exhibited the bird-type RFLP pattern. MAC isolates from 191 human patients in The
      Netherlands in 1996 were also typed by RFLP analysis. Computer-assisted analysis
      showed that the RFLP patterns of 61% of the human isolates and 59% of the porcine
      isolates were at least 75% similar to the RFLP patterns of the other group of
      strains. This indicates that pigs may be an important vehicle for M. avium
      infections in humans or that pigs and humans share common sources of infection.

PMID- 10203467
TI  - Highly sensitive methods for quantitation of human immunodeficiency virus type 1
      RNA from plasma, cells, and tissues.
AB  - Precise and sensitive quantitation of viral RNA in specimens from human
      immunodeficiency virus (HIV) type 1 (HIV-1)-infected individuals has become an
      indispensable tool for the monitoring of the efficacy of highly active
      antiretroviral combination therapy. The present report describes reproducible and
      efficient protocols with enhanced sensitivity for quantitation of HIV-1 RNA from
      plasma, peripheral blood mononuclear cells, and tissues with Qiagen silica
      columns for RNA purification combined with the Roche Amplicor HIV-1 Monitor test
      for quantitative reverse transcription-PCR (RT-PCR). Extraction of RNA from 0.5
      ml of plasma resulted in the detection of fewer than 20 HIV RNA copies/ml of
      plasma, equivalent to the centrifugation-based boosted RT-PCR assay. Silica
      extraction of cellular RNA resulted in the detection of fewer than 3 HIV-1 RNA
      copies/microg of total RNA. These techniques facilitate direct comparisons of
      viral loads between liquid and cellular specimens. Application of these sensitive
      methods may improve the assessment of the response to new antiretroviral
      regimens.

PMID- 10203468
TI  - Molecular epidemiology of tuberculosis in Malaysia.
AB  - Molecular typing with IS6110 was applied to Mycobacterium tuberculosis isolates
      from all parts of Malaysia. The degree of clustering increased with patient age,
      suggesting that reactivation may contribute to clustering. Identical banding
      patterns were also obtained for isolates from widely separate regions. Therefore,
      the use of clustering as a measure of recent transmission must be treated with
      caution. Strains related to the Beijing family were common in Peninsular Malaysia
      but were less common in Sabah and Sarawak, while a distinct group of strains
      comprised nearly 40% of isolates from East Malaysia but such strains were rare in
      Peninsular Malaysia. Single-copy strains, common in South and Southeastern Asia,
      constituted nearly 20% of isolates from the peninsula but were virtually absent
      in East Malaysia. The marked geographical difference in the prevailing strains
      indicates not only a restricted dissemination of M. tuberculosis but also a
      considerable degree of stability in the banding patterns.

PMID- 10203469
TI  - Detection and species determination of malaria parasites by PCR: comparison with
      microscopy and with ParaSight-F and ICT malaria Pf tests in a clinical
      environment.
AB  - A rapid procedure for the diagnosis of malaria infections directly from dried
      blood spots by PCR amplification was evaluated with samples from 52 patients.
      Plasmodium infections were identified with a genus-specific primer set, and
      species differentiation between Plasmodium falciparum and Plasmodium vivax was
      analyzed by multiplex PCR. The PCR test with any of the three primer sets was
      able to detect as few as four parasites per microliter by gel electrophoresis or
      by nonisotopic paper hybridization chromatography. The diagnoses obtained by PCR
      correlated closely with those obtained by Giemsa staining except for two samples
      observed to have mixed P. falciparum-P. vivax infections. These were initially
      missed by microscopic analysis. In comparison with antigen-capture assays for P.
      falciparum, the PCR assays were able to detect three infections that were missed
      by the ParaSight-F test. The PCR test was negative for nine ParaSight-F-positive
      samples and one ICT Malaria Pf-positive sample, and these were confirmed to be
      false-positive results. The PCR thus gave no false-negative or false-positive
      results. Patients undergoing antimalarial therapy were also monitored by the PCR
      assay. Four of seven patients who were PCR positive for P. vivax at the time of
      discharge were later readmitted to the hospital with a recurrence of P. vivax
      infection. We would like to propose that PCR is a sensitive and easy method that
      can serve as a useful addition to microscopy for the diagnosis and the clinical
      monitoring of treatment of malaria.

PMID- 10203470
TI  - Predictive fluorescent amplified-fragment length polymorphism analysis of
      Escherichia coli: high-resolution typing method with phylogenetic significance.
AB  - The fluorescent amplified-fragment length polymorphism (FAFLP) assay potentially
      amplifies a unique set of genome fragments from each bacterial clone. It uses
      stringently hybridizing primers which carry a fluorescent label. Precise fragment
      sizing is achieved by the inclusion of an internal size standard in every lane.
      Therefore, a unique genotype identifier(s) can be found in the form of fragments
      of precise size or sizes, and these can be generated reproducibly. In order to
      evaluate the potential of FAFLP as an epidemiological typing method with a valid
      phylogenetic basis, we applied it to 87 strains of Escherichia coli. These
      comprised the EcoR collection, which has previously been classified by multilocus
      enzyme electrophoresis (MLEE) and which represents the genetic diversity of the
      species E. coli, plus 15 strains of the clinically important serogroup O157.
      FAFLP with an unlabelled nonselective EcoRI primer (Eco+0) and a labelled
      selective MseI primer (Mse+TA) gave strain-specific profiles. Fragments of
      identical sizes (in base pairs) were assumed to be identical, and the genetic
      distances between the strains were calculated. A phylogenetic tree derived from
      measure of distance correlated closely with the MLEE groupings of the EcoR
      collection and placed the verocytotoxin-producing O157 strains on an outlier
      branch. Our data indicate that FAFLP is suitable for epidemiological
      investigation of E. coli infection, providing well-defined and reproducible
      identifiers of genotype for each strain. Since FAFLP objectively samples the
      whole genome, each strain or isolate can be assigned a place within the broad
      context of the whole species and can also be subjected to a high-resolution
      comparison with closely related strains to investigate epidemiological clonality.

PMID- 10203472
TI  - Typing of human enteroviruses by partial sequencing of VP1.
AB  - Human enteroviruses (family Picornaviridae) are the major cause of aseptic
      meningitis and also cause a wide range of other acute illnesses, including
      neonatal sepsis-like disease, acute flaccid paralysis, and acute hemorrhagic
      conjunctivitis. The neutralization assay is usually used for enterovirus typing,
      but it is labor-intensive and time-consuming and standardized antisera are in
      limited supply. We have developed a molecular typing system based on reverse
      transcription-PCR and nucleotide sequencing of the 3' half of the genomic region
      encoding VP1. The standard PCR primers amplify approximately 450 bp of VP1 for
      most known human enterovirus serotypes. The serotype of an "unknown" may be
      inferred by comparison of the partial VP1 sequence to those in a database
      containing VP1 sequences for the prototype strains of all 66 human enterovirus
      serotypes. Fifty-one clinical isolates of known serotypes from the years 1991 to
      1998 were amplified and sequenced, and the antigenic and molecular typing results
      agreed for all isolates. With one exception, the nucleotide sequences of
      homologous strains were at least 75% identical to one another (>88% amino acid
      identity). Strains with homologous serotypes were easily discriminated from those
      with heterologous serotypes by using these criteria for identification. This
      method can greatly reduce the time required to type an enterovirus isolate and
      can be used to type isolates that are difficult or impossible to type with
      standard immunological reagents. The technique may also be useful for the rapid
      determination of whether viruses isolated during an outbreak are
      epidemiologically related.

PMID- 10203471
TI  - Serological discrimination of dogs infected with gastric Helicobacter spp. and
      uninfected dogs.
AB  - Characterization of the humoral immune responses of people to Helicobacter pylori
      infection has facilitated the investigation of the host response to bacterial
      virulence factors and the development of sensitive and specific diagnostic tests.
      Dogs are commonly infected with gastric Helicobacter spp., but the presence of
      multiple Helicobacter spp. and possible coinfection in individual dogs have
      complicated serological evaluation. Evaluation of the antigenic homology of
      Helicobacter spp. revealed that the major protein bands of Helicobacter felis and
      Helicobacter bizzozeronii, two Helicobacter spp. that infect dogs, were very
      similar to UreA (29 to 31 kDa), UreB (63 to 66 kDa), and HSP (58 to 60 kDa) of H.
      pylori, and sera from infected and uninfected dogs bound in a similar way to each
      antigen. Immunoblotting and an enzyme-linked immunosorbent assay (ELISA) with H.
      felis ATCC 49179 antigen were performed with 101 serum samples (from 78 infected
      dogs and 23 uninfected dogs). Samples from uninfected dogs (median = 8) had fewer
      bands on immunoblotting than samples from infected dogs (median = 16) (P < 0.05).
      Combinations of the presence of any two of the low-molecular-mass bands (19, 25,
      30, 32, and 37 kDa) or the high-molecular-mass bands (86 and 94 kDa) were found
      almost solely in samples from infected dogs (P < 0.0001). Kinetic ELISA results
      were significantly higher for samples from infected dogs (median = 0. 0802
      optical density unit [OD]/min) than for samples from uninfected dogs (median =
      0.01428 OD/min). The combination of ELISA and immunoblotting results gave a
      specificity of 95.6% and a sensitivity of 79.8%. No correlation between ELISA
      results, colonization density, degree of inflammation, and presence of lymphoid
      follicles was observed. The results indicate substantial antigenic homology
      between H. felis, H. pylori, and H. bizzozeronii. The combination of ELISA and
      immunoblotting was a highly specific and moderately sensitive indicator of
      infection. The degree of seropositivity assessed by ELISA was not related to
      bacterial colonization density, the degree of gastric inflammation, or the
      presence of lymphoid follicles.

PMID- 10203473
TI  - Age-dependent acquisition of hepatitis G virus/GB virus C in a nonrisk
      population: detection of the virus by antibodies.
AB  - Until now there have been few seroepidemiological data for hepatitis G virus/GB
      virus type C (HGV/GBV-C). A four-antigen HGV/GBV-C immunoblot was established to
      examine 446 serum specimens from healthy individuals without risk factors for
      parenteral viral transmission. These individuals were divided into seven groups
      according to age. Seroprevalence rates were low for children and adolescents
      (5.6%) and increased for the age groups assumed to be the most sexually active
      (15.3 to 26.8%). Remarkably, none of the 80 individuals who tested positive for
      HGV/GBV-C antibodies were simultaneously positive for HGV/GBV-C viremia. From our
      data we conclude that HGV/GBV-C infection is widespread in the general population
      (16 to 25%). The development of an antibody response is associated with clearance
      of HGV/GBV-C viremia. Due to the lack of risk factors for HGV/GBV-C infection of
      blood, other efficient transmission routes must exist. It must be assumed that
      HGV/GBV-C transmission may be linked to sexual activity.

PMID- 10203475
TI  - The Cryptosporidium "mouse" genotype is conserved across geographic areas.
AB  - A 298-bp region of the Cryptosporidium parvum 18S rRNA gene and a 390-bp region
      of the acetyl coenzyme A synthetase gene were sequenced for a range of
      Cryptosporidium isolates from wild house mice (Mus domesticus), a bat (Myotus
      adversus), and cattle from different geographical areas. Previous research has
      identified a distinct genotype, referred to as the "mouse"-derived
      Cryptosporidium genotype, common to isolates from Australian mice. Comparison of
      a wider range of Australian mouse isolates with United Kingdom and Spanish
      isolates from mice and cattle and also an Australian bat-derived Cryptosporidium
      isolate revealed that the "mouse" genotype is conserved across geographic areas.
      Mice are also susceptible to infection with the "cattle" Cryptosporidium
      genotype, which has important implications for their role as reservoirs of
      infection for humans and domestic animals.

PMID- 10203474
TI  - Multicenter comparison of PCR assays for detection of human herpesvirus 8 DNA in
      semen.
AB  - Reported prevalences of human herpesvirus 8 (HHV-8) (Kaposi's sarcoma-associated
      herpesvirus) in semen have ranged widely. This is possibly due to differences in
      assay sensitivity, geographic or population-based differences in the true
      presence of the virus in semen, and PCR contamination. This study assessed
      interlaboratory sensitivity and reproducibility in the analysis of blinded
      experimental panels, each consisting of 48 specimens and being composed of semen
      specimens from different healthy artificial-insemination donors (n = 30) and
      human immunodeficiency virus (HIV)-infected patients (n = 7) plus positive (n =
      4) and negative (n = 7) controls. The experimental panels analyzed in each
      laboratory were identical except for being independently coded. Of 10 experiments
      done in five laboratories, 5 experiments from three laboratories had evidence of
      PCR contamination; all instances of contamination were in the context of nested
      PCR procedures. In the experiments with no false-positive results, HHV-8 DNA was
      detected in three (8%) of the 37 semen specimens (two from artificial
      insemination donors and one from an HIV-positive patient) but in only 3 (1.6%) of
      the 184 PCRs in which these specimens were analyzed. This suggests that HHV-8 DNA
      is present in semen at concentrations that can be too low to allow its consistent
      detection. This study emphasizes the importance of performing blinded, multi
      institution experiments to provide a coherent basis for comparing results and to
      motivate standardization of methods.

PMID- 10203476
TI  - Phenotypic and genomic variation among Staphylococcus epidermidis strains
      infecting joint prostheses.
AB  - We studied the SmaI and SstII macrorestriction patterns of 54 Staphylococcus
      epidermidis strains isolated from 14 patients infected following the implantation
      of joint prostheses. Multiple strains from pus and infected tissue specimens of
      each patient were selected on the basis of different colony morphologies and drug
      resistance patterns. The same criteria were used to select 23 S. epidermidis
      strains from hand swabs of eight healthy individuals. For 10 of the 14 patients,
      all the intrapatient strains appeared to be closely or possibly related, whereas
      related strains were detected in the skin flora of only one of the eight healthy
      individuals. This observation suggests that, in most cases, the patients were
      infected by a single S. epidermidis clone which subsequently underwent
      rearrangements that yielded derivatives with divergent phenotypes and,
      occasionally, divergent macrorestriction patterns. The four patients whose
      specimens contained unrelated S. epidermidis strains were probably infected with
      several polyclonal strains.

PMID- 10203477
TI  - Molecular characterization of a new ribotype of Vibrio cholerae O139 Bengal
      associated with an outbreak of cholera in Bangladesh.
AB  - Vibrio cholerae O139 Bengal initially appeared in the southern coastal region of
      Bangladesh and spread northward, causing explosive epidemics during 1992 and
      1993. The resurgence of V. cholerae O139 during 1995 after its transient
      displacement by a new clone of El Tor vibrios demonstrated rapid changes in the
      epidemiology of cholera in Bangladesh. A recent outbreak of cholera in two north
      central districts of Bangladesh caused by V. cholerae O139 led us to analyze
      strains collected from the outbreak and compare them with V. cholerae O139
      strains isolated from other regions of Bangladesh and neighboring India to
      investigate their origins. Analysis of restriction fragment length polymorphisms
      in genes for conserved rRNA (ribotype) revealed that the recently isolated V.
      cholerae O139 strains belonged to a new ribotype which was distinct from
      previously described ribotypes of toxigenic V. cholerae O139. All strains carried
      the genes for toxin-coregulated pili (tcpA and tcpI) and accessory colonization
      factor (acfB), the regulatory gene toxR, and multiple copies of the lysogenic
      phage genome encoding cholera toxin (CTXPhi) and belonged to a previously
      described ctxA genotype. Comparative analysis of the rfb gene cluster by PCR
      revealed the absence of a large region of the O1-specific rfb operon downstream
      of the rfaD gene and the presence of an O139-specific genomic region in all O139
      strains. Southern hybridization analysis of the O139-specific genomic region also
      produced identical restriction patterns in strains belonging to the new ribotype
      and those of previously described ribotypes. These results suggested that the new
      ribotype of Bengal vibrios possibly originated from an existing strain of V.
      cholerae O139 by genetic changes in the rRNA operons. In contrast to previously
      isolated O139 strains which mostly had resistance to trimethoprim,
      sulfamethoxazole, and streptomycin encoded by a transposon (SXT element), 68.6%
      of the toxigenic strains analyzed in the present study, including all strains
      belonging to the new ribotype, were susceptible to these antibiotics. Molecular
      analysis of the SXT element revealed possible deletion of a 3.6-kb region of the
      SXT element in strains which were susceptible to the antibiotics. Thus, V.
      cholerae O139 strains in Bangladesh are also undergoing considerable
      reassortments in genetic elements encoding antimicrobial resistance.

PMID- 10203478
TI  - Recurrent "Flexispira rappini" bacteremia in an adult patient undergoing
      hemodialysis: case report.
AB  - A blood culture from a 65-year-old febrile man undergoing hemodialysis revealed,
      5 days after inoculation, an unusual gram-negative fusiform rod with darting
      motility. During another episode of fever 21 days later, this Campylobacter-like
      organism was again recovered from three blood cultures and subcultured under an
      H2-enriched microaerobic atmosphere. The organism was catalase negative and
      oxidase positive and hydrolyzed urea rapidly. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis analysis of whole-cell proteins was
      indistinguishable from that of "Flexispira rappini" LMG 8738 described by Archer
      et al. in 1988 (J. R. Archer, S. Romero, A. E. Ritchier, M. E. Hamacher, B. M.
      Steiner, J. H. Bryner, and R. F. Schell, J. Clin. Microbiol. 26:101-105, 1988).
      The analysis of the 16S ribosomal DNA sequence revealed a similarity of 99.3%
      between the two strains. The patient recovered completely after a 4-week course
      of meropenem therapy. This is the first reported case of a recurrent "F. rappini"
      bacteremia in an adult patient, which confirms that this organism may be an
      invasive pathogen in immunocompromised patients, like other newly described
      Helicobacter species.

PMID- 10203479
TI  - Evaluation of the INNO-LIA HTLV I/II assay for confirmation of human T-cell
      leukemia virus-reactive sera in blood bank donations.
AB  - We have evaluated a new serological confirmatory test (INNO-LIA HTLV I/II Ab
      [INNO-LIA]) for human T-cell leukemia virus (HTLV) using a large collection of
      samples from Brazilian blood donors (Sao Paulo region) and compared the results
      with those obtained by Western blotting (WB) tests (WB2.3 and WB2.4). Blood
      donations were initially screened by enzyme-linked immunosorbent assays (ELISAs)
      based on viral lysates, and repeatedly reactive samples were further tested by
      WB2.3. When available, samples were also tested by PCR, two additional ELISAs
      based on recombinant antigens (recombinant ELISAs), a new-generation WB assay
      (WB2.4), and the INNO-LIA. Of the 18,169 samples tested, 292 (1.61%) were
      repeatedly reactive in the ELISAs (viral lysate based) and were further tested by
      WB2.3; 97 were positive (19 that were typed as HTLV type I [HTLV-I], 12 that were
      typed as HTLV type II [HTLV-II], and 66 that were nontypeable), 17 were negative,
      and 178 had indeterminate results. Of the samples with indeterminate results, 172
      were tested by INNO-LIA, which could resolve 153 samples as negative. Regarding
      the positive samples, WB2. 3 and INNO-LIA produced concordant results for all
      HTLV-I-positive samples, whereas for HTLV-II they agreed for 10 of 12 samples;
      the 2 samples with discordant results were considered to be positive for HTLV-II
      by WB with WB2.3 but negative for HTLV-II by INNO-LIA and the two recombinant
      ELISAs. Furthermore, of the 66 nontypeable samples, 60 underwent testing by INNO
      LIA; 54 turned out to be negative by the latter test as well as by recombinant
      ELISAs. In conclusion, the new serological confirmatory assay for HTLV (INNO-LIA
      HTLV I/II Ab) resolved the results for the majority of the indeterminate and
      positive-untypeable samples frequently observed by WB assays.

PMID- 10203481
TI  - Evidence of the human granulocytic ehrlichiosis agent in Ixodes ricinus ticks in
      Switzerland.
AB  - A total of 1,667 Ixodes ricinus ticks were collected from five regions in
      Switzerland where there have been sporadic occurrences of granulocytic
      ehrlichiosis in dogs and horses. The ticks were examined for rickettsiae of the
      Ehrlichia phagocytophila group via nested PCR. Twenty-one ticks (1.3%) were
      positive; 3 (0.5%) were nymphs, 6 (1.3%) were adult males, and 12 (1.9%) were
      adult females. The number of positive ticks varied with the stage of development
      and with the geographical origin. Nucleotide sequencing of the isolated PCR
      products identified these products as part of the 16S rRNA gene of Ehrlichia. In
      addition, these products had 100% homology with the agent of human granulocytic
      ehrlichiosis. The occurrence of this agent in I. ricinus in Switzerland presents
      a potential danger of transmission of granulocytic ehrlichiosis to dogs, horses,
      and humans.

PMID- 10203480
TI  - Quantitative real-time PCR for detection of members of the Ehrlichia
      phagocytophila genogroup in host animals and Ixodes ricinus ticks.
AB  - A TaqMan PCR was established for identification and quantitation of members of
      the Ehrlichia phagocytophila group in experimentally infected cows and in Ixodes
      ricinus ticks. The TaqMan PCR identified a 106-bp section of the 16S rRNA gene by
      use of a specific fluorogenic probe and two primers. This technique was specific
      for members of the E. phagocytophila group, which include E. phagocytophila,
      Ehrlichia equi, and the agent of human granulocytic ehrlichiosis. The TaqMan
      system identified 10 copies of a cloned section of the 16S rRNA gene of E.
      phagocytophila. The sensitivity and specificity of the TaqMan PCR were similar to
      those of conventional nested PCR. The numbers of ehrlichiae in leukocytes of the
      two cows experimentally infected with E. phagocytophila were measured daily by
      TaqMan PCR and had a course similar to that of the percentages of infected
      leukocytes determined daily by light microscopy. The prevalence of infected free
      living ticks, which were collected from areas where bovine ehrlichiosis is
      endemic and from regions with sporadic occurrences of granulocytic ehrlichiosis
      in dogs and horses, was identical as determined by nested PCR and TaqMan PCR.

PMID- 10203482
TI  - Discrimination of Burkholderia multivorans and Burkholderia vietnamiensis from
      Burkholderia cepacia genomovars I, III, and IV by PCR.
AB  - We present a PCR procedure for identification of Burkholderia cepacia,
      Burkholderia multivorans, and Burkholderia vietnamiensis. 16S and 23S ribosomal
      DNAs (rDNAs) of B. multivorans and B. vietnamiensis were sequenced and aligned
      with published sequences for definition of species-specific 18-mer
      oligonucleotide primers. Specific antisense 16S rDNA primers (for B. cepacia, 5'
      AGC ACT CCC RCC TCT CAG-3'; for B. multivorans, 5'-AGC ACT CCC GAA TCT CTT-3')
      and 23S rDNA primers (for B. vietnamiensis, 5'-TCC TAC CAT GCG TGC AA-3') were
      paired with a general sense primer of 16S rDNAs (5'-AGR GTT YGA TYM TGG CTC AG
      3') or with a sense primer of 23S rDNA (5'-CCT TTG GGT CAT CCT GGA-3'). PCR with
      these primers under optimized conditions is appropriate to specifically and
      rapidly identify B. multivorans, B. vietnamiensis, and B. cepacia (genomovars I,
      III, and IV are not discriminated). In comparison with the polyphasic taxonomic
      analyses presently necessary for species and genomovar identification within the
      B. cepacia complex, our procedure is more rapid and easier to perform and may
      contribute to clarifying the clinical significance of individual members of the
      complex in cystic fibrosis.

PMID- 10203483
TI  - GB virus C/hepatitis G virus groups and subgroups: classification by a
      restriction fragment length polymorphism method based on phylogenetic analysis of
      the 5' untranslated region.
AB  - A phylogenetic tree based on 150 5' untranslated region sequences deposited in
      GenBank database allowed segregation of the sequences into three major groups,
      including two subgroups, i.e., 1, 2a, 2b, and 3, supported by bootstrap analysis.
      Restriction site analysis of these sequences predicted that HinfI and either
      AatII or AciI could be used for genomic typing with 99.4% accuracy. cDNA
      sequencing and subsequent alignment of 21 Argentine GB virus C/hepatitis G virus
      strains confirmed restriction fragment length polymorphism patterns theoretically
      predicted. This method may be useful for a rapid screening of samples when either
      epidemiological or transmission studies of this agent are carried out.

PMID- 10203485
TI  - Laboratory diagnosis of common viral infections of the central nervous system by
      using a single multiplex PCR screening assay.
AB  - A multiplex PCR assay that detects the four commonest causes of viral meningitis
      and encephalitis in the United Kingdom (herpes simplex virus [HSV] type 1 [HSV
      1], HSV type 2 [HSV-2], varicella-zoster virus [VZV], and enteroviruses) was
      developed, and its sensitivity was compared with those of similar assays
      described previously for this application. Compared to the previous assays, this
      single multiplex PCR assay had higher molecular sensitivities for the detection
      for each of the viruses and improved utility for routine use in a diagnostic
      laboratory. The assay was used to test a series of 1,683 consecutive
      cerebrospinal fluid (CSF) samples between June 1997 and March 1998 inclusively.
      Viral nucleic acid was detected in 138 (8.2%) of the CSF samples, including
      enteroviruses in 51 samples, HSV-2 in 33 samples, VZV in 28 samples, and HSV-1 in
      25 samples. Compared to the accepted relative incidence of viral etiologies,
      aseptic meningitis due to HSV-2 infection was high, and in adult female patients
      with symptoms of aseptic meningitis, HSV-2 was the virus most commonly detected
      in the CSF.

PMID- 10203484
TI  - Detection of multidrug-resistant Salmonella enterica serotype typhimurium DT104
      based on a gene which confers cross-resistance to florfenicol and
      chloramphenicol.
AB  - Salmonella enterica serotype typhimurium (S. typhimurium) DT104 (DT104) first
      emerged as a major pathogen in Europe and is characterized by its pentadrug
      resistant pattern. It has also been associated with outbreaks in the United
      States. The organism typically carries resistance to ampicillin, chloramphenicol,
      streptomycin, sulfonamides, and tetracycline. The mechanism of chloramphenicol
      resistance in DT104 was determined by producing antibiotic-resistant Escherichia
      coli host strain clones from DT104 DNA. DNA from chloramphenicol-resistant clones
      was sequenced, and probes specific for the genes floS. typhimurium (floSt), int,
      invA, and spvC were produced for colony blot hybridizations. One hundred nine
      Salmonella isolates, including 44 multidrug-resistant DT104 isolates, were tested
      to evaluate the specificities of the probes. The gene floSt, reported in this
      study, confers chloramphenicol and florfenicol resistance on S. typhimurium
      DT104. Florfenicol resistance is unique to S. typhimurium DT104 and multidrug
      resistant S. typhimurium isolates with the same drug resistance profile among all
      isolates evaluated. Of 44 DT104 isolates tested, 98% were detected based on
      phenotypic florfenicol resistance and 100% had the floSt-positive genotype.
      Resistances to florfenicol and chloramphenicol are conferred by the gene floSt,
      described in this paper. Presumptive identification of S. typhimurium DT104 can
      be made rapidly based on the presence of the floSt gene or its resulting
      phenotype.

PMID- 10203488
TI  - Comparison of the mycobacteria growth indicator tube with MB redox, Lowenstein
      Jensen, and Middlebrook 7H11 media for recovery of mycobacteria in clinical
      specimens.
AB  - The rate of recovery and the mean time to detection of mycobacteria in clinical
      specimens were evaluated with two nonradiometric broth-based systems, the
      Mycobacteria Growth Indicator Tube (MGIT) and MB Redox systems. The data obtained
      for each system were compared with each other and with those obtained with the
      Lowenstein-Jensen (LJ) and Middlebrook 7H11 reference media. A total of 117
      mycobacterial isolates (Mycobacterium tuberculosis, n = 112; nontuberculous
      mycobacteria, n = 5) were detected in 486 clinical specimens. The recovery rates
      for M. tuberculosis were 91 of 112 (81.3%) isolates with MGIT and 81 of 112
      (72.3%) isolates with MB Redox. The combination of MGIT plus MB Redox recovered
      104 of the 112 (92.9%) M. tuberculosis isolates. MGIT plus LJ plus Middlebrook
      7H11 recovered 106 of the 112 (94.6%) isolates, MB Redox plus LJ plus Middlebrook
      7H11 recovered 99 of the 112 (88.4%) isolates, and LJ plus Middlebrook 7H11
      recovered 84 of the 112 (75. 0%) isolates. The mean time to detection of M.
      tuberculosis in smear-positive specimens was 7.2 days with MGIT, 6.9 days with MB
      Redox, 20.4 days with LJ, and 17.6 days with Middlebrook 7H11. The mean time to
      detection of M. tuberculosis in smear-negative specimens was 19.1 days with MGIT,
      15.5 days with MB Redox, 25.8 days with LJ, and 21.6 days with Middlebrook 7H11.
      The contamination rates were 4.4, 3.8, 2.1, and 2.7% for MGIT, MB Redox, LJ, and
      Middlebrook 7H11, respectively. In conclusion, MGIT and MB Redox can be viable
      tools in the routine mycobacteriology laboratory.

PMID- 10203487
TI  - Prevalence of Borrelia burgdorferi in Ixodes ricinus ticks in urban recreational
      areas of Helsinki.
AB  - Lyme borreliosis, an infection caused by the tick-borne spirochete Borrelia
      burgdorferi, is a major health problem for populations in areas of endemicity in
      the Northern Hemisphere. In the present study we assessed the density of ticks
      and the prevalence of B. burgdorferi sensu lato among ticks in popular urban
      recreational areas of Helsinki, Finland. Altogether 1,688 Ixodes ricinus ticks
      were collected from five areas located within 5 km of the downtown section of
      Helsinki, and 726 of them (303 nymphs, 189 females, and 234 males) were randomly
      chosen for laboratory analysis. The midguts of the ticks were divided into three
      pieces, one for dark-field microscopy, one for cultivation in BSK-II medium, and
      one for PCR analysis. Ticks were found in all the study areas; their densities
      varied from 1 to 36 per 100 m along which a cloth was dragged. The rate of tick
      infection with B. burgdorferi sensu lato varied from 19 to 55%, with the average
      being 32%. Borellia afzelii was the most predominant genospecies in all the
      areas, and no B. burgdorferi sensu stricto isolates were detected. Only two ticks
      were concurrently infected with both B. afzelii and Borrelia garinii. Dark-field
      microscopy gave more positive results for B. burgdorferi than did cultivation or
      PCR analysis. However, the agreement between all three methods was fairly good.
      We conclude that Lyme borreliosis can be contracted even in urban environments
      not populated with large mammals like deer or elk. The disease should be taken
      into account in the differential diagnosis of certain symptoms of patients from
      these areas, and the use of measures to improve the awareness of the general
      population and health care officials of the risk of contracting the disease is
      warranted.

PMID- 10203489
TI  - Characterization of nonenterotoxigenic Escherichia coli strains producing F17
      fimbriae isolated from diarrheic lambs and goat kids.
AB  - Forty-five ovine and caprine nonenterotoxigenic Escherichia coli strains
      producing F17-related fimbriae were characterized with respect to the fimbrial
      structural subunit and adhesin subtypes produced. In addition, several
      characteristics related to the virulence of strains producing F17 fimbriae were
      studied. Most of the strains (73%) possessed the f17cA structural subunit gene,
      whereas the f17aA and f17dA genes were detected only on three (6%) and two (4%)
      strains, respectively. The f17bA gene was not detected. All but one of these
      strains possessed the f17G genes of the adhesin subfamily II. The only strain
      having the f17G gene of subfamily I possessed the structural subunit gene f17dA.
      Sequencing of the f17A and f17G genes of four selected strains confirmed the
      association of f17cA and f17dA structural subunit genes with the f17G genes of
      the adhesin subfamily II. These results indicated that adhesins of the subfamily
      II are prominent among ovine and caprine isolates and that they are indistinctly
      associated with the F17 structural subunit subtypes on these field strains. CS31A
      and CNF2-related genes were not detected. Most of the strains adhered in vitro
      to ovine intestinal brush borders (36 of 45) and agglutinated the erythrocytes of
      different species in the presence of D-mannose (39 of 45). F17-positive strains
      produced colicin V (57%) and were resistant to the bactericidal effect of serum
      (91%) in significantly higher percentages than F17-negative strains (34% produced
      colicin V, and 66% were serum resistant). Thus, most of the studied ovine and
      caprine strains showed phenotypic characteristics of septicemic strains.

PMID- 10203486
TI  - Discrimination of subtype B and non-subtype B strains of human immunodeficiency
      virus type 1 by serotyping: correlation with genotyping.
AB  - The ability of a peptide-based serotyping assay to differentiate human
      immunodeficiency virus (HIV) type 1 (HIV-1) subtype B infections from non-subtype
      B infections was investigated with 166 anti-HIV-1- and HIV RNA-positive (by PCR)
      serum or plasma specimens. The specimens were divided genetically into those
      infected with subtype B and non-subtype B by application of a screening
      heteroduplex mobility assay (HMA) that used plasmids for subtypes A and B alone.
      Specimens that were not clearly infected with HIV-1 subtype B by HMA or for which
      the two methods had discordant results in distinguishing those infected with
      subtype B from those infected with non-subtype B were then investigated with a
      full HMA plasmid panel and, for selected specimens, env sequencing. For the 141
      genotyped and serotypically reactive specimens, the correlation between
      genotyping and serotyping (all subtypes) was 69%. Of the 67 specimens that
      reacted monotypically as serotype B, 64 were shown to be infected with genotype B
      (positive predictive value, 96%). Of the 82 specimens that contained genotype B
      nucleic acid, 64 reacted monotypically as serotype B (sensitivity, 78%), and 4
      specimens reacted with a single non-subtype B peptide; the viruses in 14
      specimens could not be assigned a serotype. Initial screening results had
      indicated that 12 samples had results discordant between restricted HMA and
      serotyping. The V3 loop amino acids of the infecting HIV strains from the seven
      specimens with discordant serology results were analyzed. For five specimens
      discordance occurred when the amino acid sequence of the infecting virus closely
      resembled those of more than one consensus peptide antigen or when the observed
      V3 crown motif of the strain was atypical for the genetic subtype present. For
      the other two specimens no explanation for the discordance was identified. Five
      specimens gave unclear or discordant results in the initial HMA screen, but the
      results were resolved when the full plasmid panel was used. Serotyping, although
      of limited sensitivity, distinguishes between subtype B and non-subtype B
      infections with a high degree of specificity. However, it poorly differentiates
      the major non-subtype B subtypes, particularly subtypes A and C. When HIV-1
      subtype B predominates, serological typing and/or subtype-restricted HMA
      screening usefully distinguishes between subtype B and non-subtype B infections.

PMID- 10203490
TI  - High aspartyl proteinase production and vaginitis in human immunodeficiency virus
      infected women.
AB  - Vaginal isolates of Candida albicans from human immunodeficiency virus-positive
      (HIV+) and HIV- women with or without candidal vaginitis were examined for
      secretory aspartyl proteinase (Sap) production in vitro and in vivo and for the
      possible correlation of Sap production with pathology and antimycotic
      susceptibility in vitro. HIV+ women with candidal vaginitis were infected by
      strains of C. albicans showing significantly higher levels of Sap, a virulence
      enzyme, than strains isolated from HIV+, C. albicans carrier subjects and HIV-
      subjects with vaginitis. The greater production of Sap in vitro was paralleled by
      greater amounts of Sap in the vaginal fluids of infected subjects. In an estrogen
      dependent, rat vaginitis model, a strain of C. albicans producing a high level of
      Sap that was isolated from an HIV+ woman with vaginitis was more pathogenic than
      a strain of C. albicans that was isolated primarily from an HIV-, Candida
      carrier. In the same model, pepstatin A, a strong Sap inhibitor, exerted a strong
      curative effect on experimental vaginitis. No correlation was found between Sap
      production and antimycotic susceptibility, as most of the isolates were fully
      susceptible to fluconazole, itraconazole, and other antimycotics, regardless of
      their source (subjects infected with strains producing high or low levels of Sap,
      subjects with vaginitis or carrier subjects, or subjects with or without HIV).
      Thus, high Sap production is associated with virulence of C. albicans but not
      with fungal resistance to fluconazole in HIV-infected subjects, and Sap is a
      potentially new therapeutic target in candidal vaginitis.

PMID- 10203491
TI  - Evaluation of human seroreactivity to Bartonella species in Sweden.
AB  - Among the species that compose the expanding genus Bartonella, thus far only B.
      henselae and B. quintana have reportedly been isolated from humans in Europe. To
      evaluate the prevalence of Bartonella infection in Sweden, we conducted a
      retrospective serological examination of 126 human serum samples. These samples
      were analyzed for antibodies to B. henselae, B. quintana, and B. elizabethae.
      Serum samples from 100 blood donors, who spanned the ages of 20 to 60 and had no
      apparent clinical signs of illness, were also studied as a control group. An
      immunoglobulin G indirect fluorescence antibody assay revealed 4 and 8.3%
      Bartonella positivity rates for the blood donor and patient group, respectively,
      when a cutoff titer of >/=64 was chosen. Among the blood donors, four were
      seropositive to B. elizabethae; one of these also had concordant positive titer
      to B. henselae. In the patient group, 14 serum samples were positive against
      Bartonella spp. These serum specimens represented nine patients. In three of
      these seropositive patients, paired serum samples displayed a fourfold increase
      in antibody titer to at least one of the three antigens. These three patients are
      discussed. In this report we also present a case study of a 60-year-old Swedish
      male with fatal myocarditis. Postmortem serological analysis revealed a high
      titer against B. elizabethae. PCR and nucleotide sequencing of the myocardial
      tissue from this patient, and of liver tissue from one of the other three
      patients, showed sequences similar to B. quintana. The age, geographical origin,
      animal contacts, and serological response pattern to the different Bartonella
      antigens differed among the four patients. This study substantiates the presence
      of Bartonella spp. in Sweden, documents the seroreactivity to three Bartonella
      antigens in Swedish patients, and reports the first two cases of B. quintana-like
      infections in Sweden.

PMID- 10203492
TI  - Detection by enzyme immunoassay of serum immunoglobulin G antibodies that
      recognize specific Cryptosporidium parvum antigens.
AB  - Human infection with Cryptosporidium parvum usually elicits characteristic
      immunoglobulin G (IgG), IgA, and IgM antibody responses against two sporozoite
      surface antigens with apparent molecular masses of approximately 27 and 17 kDa.
      We have determined that these two antigens are actually complex families of
      related antigens. We have developed two new enzyme-linked immunosorbent assays
      (ELISAs) for the detection and quantitation of serum IgG antibodies against both
      antigens. The assays utilize a recombinant form of the 27-kDa antigen and a
      partially purified native fraction isolated from sonicated whole oocysts that
      contains 17-kDa antigen. An immunoblot assay previously developed in our
      laboratory served as the reference, or "gold standard," seroassay for the
      assessment of the new ELISAs. Positive responses with the recombinant-27-kDa
      antigen ELISA were correlated with the immunoblot results for the 27-kDa antigen,
      with a sensitivity and specificity of 90 and 92%, respectively. Similarly,
      positive responses with the partially purified native-17-kDa-antigen ELISA
      correlated with the immunoblot results for the 17-kDa antigen, with a sensitivity
      and specificity of 90 and 94%, respectively. For both ELISAs the median IgG
      antibody levels for serum sets collected during outbreaks of waterborne C. parvum
      infection were at least 2.5-fold higher than the levels determined for a
      nonoutbreak set. Using the immunoblot as the "gold standard," the new ELISAs were
      more specific and, in the case of the 27-kDa-antigen ELISA, more sensitive than
      the crude oocyst antigen ELISA currently in use. These assays will be useful in
      future epidemiologic studies.

PMID- 10203493
TI  - Use of a novel hepatitis C virus (HCV) major-epitope chimeric polypeptide for
      diagnosis of HCV infection.
AB  - The genome of hepatitis C virus (HCV) consists of seven functional regions: the
      core, E1, E2/NS1, NS2, NS3, NS4, and NS5 regions. The U. S. Food and Drug
      Administration-licensed 2.0G immunoassay for the detection of anti-HCV uses
      proteins from the core, NS3, and NS4 regions (McHutchinson et al., Hepatology
      15:19-25, 1992). The 3.0G enzyme-linked immunosorbent assay includes the protein
      from the NS5 region (Uyttendaele et al., Vox Sang. 66:122-129, 1994). The
      necessity of detecting antibodies to viral envelope proteins (E1 and E2) and to
      different genotype samples has been demonstrated previously (Chien et al., Lancet
      342:933, 1993; Lok et al., Hepatology 18:497-502, 1993). In this study we have
      attempted to improve the sensitivity of the anti-HCV assay by developing a single
      multiple-epitope fusion antigen (MEFA; MEFA-6) which incorporates all of the
      major immunodominant epitopes from the seven functional regions of the HCV
      genome. A nucleic acid sequence consisting of proteins from the viral core, E1,
      E2, NS3, NS4, and NS5 regions and different subtype-specific regions of the NS4
      region was constructed, cloned, and expressed in yeast. The epitopes present on
      this antigen can be detected by epitope-specific monoclonal and polyclonal
      antibodies. In a competition assay, the MEFA-6 protein competed with 83 to 96% of
      genotype-specific antibodies from HCV genotype-specific peptides. This
      recombinant antigen was subsequently used to design an anti-HCV chemiluminescent
      immunoassay. We designed our assay using a monoclonal anti-human immunoglobulin G
      antibody bound to the solid phase. Because MEFA-6 is fused with human superoxide
      dismutase (h-SOD), we used an anti-human superoxide dismutase, dimethyl
      acridinium ester-labeled monoclonal antibody for detection. Our results indicate
      that MEFA-6 exposes all of the major immunogenic epitopes. Its excellent
      sensitivity and specificity for the detection of clinical seroconversion are
      demonstrated by this assay.

PMID- 10203494
TI  - Postsurgical Candida albicans infections associated with an extrinsically
      contaminated intravenous anesthetic agent.
AB  - From 16 to 30 April 1990, four of 364 (1%) postsurgical patients at one hospital
      developed Candida albicans fungemia or endophthalmitis. The case patients'
      surgeries were clustered on two days. To identify risk factors for C. albicans
      infections, we conducted a cohort study comparing these 4 patients with 67
      control patients who had surgeries on the same days but did not acquire C.
      albicans infections. The participation of anesthesiologist 9 (relative risk [RR],
      undefined; P < 0.001) and receipt of intravenous propofol, an anesthetic agent
      without preservative, which was administered by an infusion pump (RR, 8.8; P =
      0.048) were identified as risk factors for C. albicans infections. The anesthetic
      had been recently introduced in the hospital. Hand cultures of 8 of 14 (57%)
      anesthesiologists were positive for Candida species; one yielded C. albicans.
      Anesthesiologist 9 was the only one to use stored syringes of propofol in the
      infusion pump and to reuse propofol syringes. DNA fingerprinting with a
      digoxigenin-labeled C. albicans repetitive element 2 probe and electrophoretic
      karyotyping showed two distinct banding patterns among patient isolates. We
      hypothesize that extrinsic contamination of propofol by anesthesiologist 9 likely
      resulted in C. albicans infections. These data suggest that strict aseptic
      techniques must be used when preparing and administering propofol.

PMID- 10203495
TI  - Relatedness analyses of Histoplasma capsulatum isolates from Mexican patients
      with AIDS-associated histoplasmosis by using histoplasmin electrophoretic
      profiles and randomly amplified polymorphic DNA patterns.
AB  - The present paper analyzes the histoplasmin electrophoretic profiles and the
      randomly amplified polymorphic DNA (RAPD) patterns of the fungus Histoplasma
      capsulatum isolated from Mexican patients with AIDS-associated histoplasmosis.
      Clinical isolates from Guatemala, Colombia, and Panama, as well as H. capsulatum
      isolates from different sources in nature, were also processed. All histoplasmin
      samples shared four antigenic fractions of 200, 49, 10.5, and 8.5 kDa in sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). According to their
      percentage of relatedness, based on SDS-PAGE histoplasmin electrophoretic image
      analysis, H. capsulatum isolates were divided in two groups: group A contained
      all AIDS-associated isolates studied and two human reference strains from Mexican
      histoplasmosis patients without AIDS; group B included bat guano, infected bat,
      and cock excreta isolates from the State of Guerrero, Mexico, plus three human
      histoplasmosis strains from Guatemala, Panama, and Colombia. Polymorphic DNA
      patterns evaluated by RAPD-PCR showed three major bands of 4.4, 3.2, and 2.3 kb
      in most H. capsulatum isolates studied. Four groups were related by DNA
      polymorphisms: group I was formed by most of the AIDS-associated H. capsulatum
      isolates studied, one human histoplasmosis strain from Colombia, two human
      reference strains from Mexican patients without AIDS, and one human
      histoplasmosis strain from Guatemala. Group II consisted of only a single strain
      from Panama. Group III included three strains: one from a Mexican patient with
      AIDS and two isolated from nature in Guerrero (cock excreta and bat guano). The
      last, group IV, consisted of only one strain isolated from an infected bat,
      captured in Guerrero. A tight relationship between phenotypic and genotypic
      characterization was observed, and both analyses could be useful tools for typing
      H. capsulatum from different sources and geographic origins.

PMID- 10203496
TI  - Multicenter quality assessment of PCR methods for detection of enteroviruses.
AB  - We conducted a multicenter evaluation of commercial and in-house PCR methods for
      the detection of enteroviruses. Three coded panels of test and control RNA
      samples, artificial clinical specimens, and representative enterovirus serotypes
      were used to assess amplification methods, RNA extraction methods, and
      reactivities with different enterovirus serotypes. Despite several differences
      between PCR methods, there was good agreement, although some variation in
      sensitivity was observed. Most PCR methods were able to detect enterovirus RNA
      derived from 0.01 50% tissue culture infective dose (TCID50) and were able to
      detect at least 1 TCID50 of enterovirus in cerebrospinal fluid, stool, or throat
      swab specimens. Most were also able to detect a wide range of enterovirus
      serotypes, although serotypic identification was not possible. Some laboratories
      experienced false-positive results due to PCR contamination, which appeared to
      result mainly from cross-contamination of specimens during RNA extraction.
      Provided that this problem is overcome, these PCR methods will prove to be a
      sensitive and rapid alternative to cell culture for the diagnosis of enterovirus
      infection.

PMID- 10203497
TI  - Clinical and financial benefits of rapid bacterial identification and
      antimicrobial susceptibility testing.
AB  - To assess the expected clinical and financial benefits of rapid reporting of
      microbiology results, we compared patients whose cultured samples were processed
      in the normal manner to patients whose samples were processed more rapidly due to
      a minor change in work flow. For the samples tested in the rapid-reporting time
      period, the vast majority of bacterial identification and antimicrobial
      susceptibility testing (AST) results were verified with the Vitek system on the
      same day that they were available. This time period was called rapid AST (RAST).
      For RAST, a technologist on the evening shift verified the data that became
      available during that shift. For the control time period, cultures were processed
      in the normal manner (normal AST [NAST]), which did not include evening-shift
      verification. For NAST, the results for approximately half of the cultures were
      verified on the first day that the result was available. The average turnaround
      time for the reporting of AST results was 39.2 h for RAST and 44.4 h for NAST
      (5.2 h faster for RAST [P = 0.001]). Subsequently, physicians were able to
      initiate appropriate antimicrobial therapy sooner for patients whose samples were
      tested as part of RAST (P = 0.006). The mortality rates were 7. 9 and 9.6% for
      patients whose samples were tested as part of RAST and NAST, respectively (P =
      0.45). The average length of stay was 10. 7 days per patient for RAST and 12.6
      days for NAST, a difference of 2.0 days less for RAST (P = 0.006). The average
      variable cost was $4, 927 per patient for RAST and $6,677 for NAST, a difference
      of $1,750 less per patient for RAST (P = 0.001). This results in over $4 million
      in savings in variable costs per year in our hospital.

PMID- 10203498
TI  - Clinical evaluation of the enhanced Gen-Probe Amplified Mycobacterium
      Tuberculosis Direct Test for rapid diagnosis of tuberculosis in prison inmates.
AB  - The reliability of the enhanced Amplified Mycobacterium Tuberculosis Direct Test
      (E-MTD; Gen-Probe, Inc., San Diego, Calif.) for rapid diagnosis of pulmonary
      tuberculosis (TB) was evaluated by testing 1, 004 respiratory specimens from 489
      Texas prison inmates. Results were compared to those of mycobacterial culture
      (BACTEC TB 460 and Middlebrook 7H11 biplates), smear for acid-fast bacilli (AFB;
      auramine O), and clinical course. After chart review, three patients (nine
      specimens) who were on antituberculosis therapy before the study began were
      excluded from final analysis. Of the remaining 995 specimens, 21 were AFB smear
      positive: 13 grew Mycobacterium tuberculosis complex (MTBC), 6 grew
      nontuberculous mycobacteria, and 2 (from two patients diagnosed with TB and
      started on therapy after the study began) were culture negative. Twenty-eight
      specimens (20 patients) were positive for MTBC by culture and E-MTD. Seven
      specimens (seven patients) were positive by culture alone; three were from
      patients who had other E-MTD-positive specimens, two were false-positive
      cultures, and two were false-negative E-MTD results. Eight specimens were
      positive by E-MTD only; four specimens (four patients) were false-positive E-MTD
      results, and four specimens were from two patients with earlier E-MTD-positive
      specimens that grew MTBC. Thus, there were 22 patients with TB (10 smear positive
      and 12 smear negative). The sensitivity and specificity of the AFB smear for
      diagnosis of TB, by patient, were 45.5 and 98.9%, respectively. After resolving
      discrepancies, these same values for E-MTD were 90.9 and 99.1% overall, 100 and
      100% for the smear-positive patients, and 83.3 and 99.1% for the smear-negative
      patients. Excluding the one smear-negative patient whose E-MTD-negative, MTBC
      culture-positive specimen contained inhibitory substances, the sensitivity of E
      MTD was 95.2% overall and 90.9% in smear-negative patients. The specificity and
      positive predictive value of E-MTD can be improved, without altering other
      performance characteristics, by modifying the equivocal zone recommended by the
      manufacturer. These data suggest that E-MTD is a reliable method for rapid
      diagnosis of pulmonary TB, irrespective of the AFB smear result. Guidelines for
      the most appropriate use of E-MTD with smear-negative patients are needed.

PMID- 10203499
TI  - Distribution of Porphyromonas gingivalis strains with fimA genotypes in
      periodontitis patients.
AB  - Fimbriae (FimA) of Porphyromonas gingivalis are filamentous components on the
      cell surface and are thought to play an important role in the colonization and
      invasion of periodontal tissues. We previously demonstrated that fimA can be
      classified into four variants (types I to IV) on the basis of the nucleotide
      sequences of the fimA gene. In the present study, we attempted to detect the four
      different fimA genes in saliva and plaque samples isolated from patients with
      periodontitis using the PCR method. Four sets of fimA type-specific primers were
      designed for the PCR assay. These primers selectively amplified 392-bp (type I),
      257-bp (type II), 247-bp (type III), and 251-bp (type IV) DNA fragments of the
      fimA gene. Positive PCR results were observed with reference strains of P.
      gingivalis in a type-specific manner. All other laboratory strains of oral and
      nonoral bacteria gave negative results. The sensitivity of the PCR assay for fimA
      type-specific detection was between 5 and 50 cells of P. gingivalis. Clinical
      samples were obtained from saliva and subgingival plaque from deep pockets (>/=4
      mm) of 93 patients with periodontitis. Bacterial genomic DNA was isolated from
      the samples, and the targeted fragments were amplified by PCR. The presence of P.
      gingivalis was demonstrated in 73 patients (78.5%), and a single fimA gene was
      detected in most patients. The distribution of the four fimA types among the P.
      gingivalis-positive patients was as follows: type I, 5.4%; type II, 58.9%; type
      III, 6. 8%; type IV, 12.3%; types I and II, 6.8%; types II and IV, 2.7%; and
      untypeable, 6.8%. P. gingivalis with type II fimA was detected more frequently in
      the deeper pockets, and a significant difference of the occurrence was observed
      between shallow (4 mm) and deep (>/=8 mm) pockets. These results suggest that P.
      gingivalis strains that possess type II fimA are significantly more predominant
      in periodontitis patients, and we speculate that these organisms are involved in
      the destructive progression of periodontal diseases.

PMID- 10203500
TI  - Comparison of cytomegalovirus loads in plasma and leukocytes of patients with
      cytomegalovirus retinitis. The Cytomegalovirus Retinitis and Viral Resistance
      Study Group.
AB  - Cytomegalovirus (CMV) DNA loads in paired leukocyte and plasma samples from 199
      patient visits by 66 patients with CMV retinitis were determined. Leukocyte CMV
      load determinations had a greater range of values (mean, 24,587 copies/10(6)
      leukocytes; maximum, 539, 000) than did plasma CMV load determinations (mean,
      10,302 copies/ml; maximum, 386,000), and leukocyte viral loads were detectable in
      a greater proportion of patients at the time of diagnosis of CMV retinitis prior
      to initiation of anti-CMV therapy (82%) than were plasma viral loads (64%) (P =
      0.0078). Agreement with CMV blood cultures was slightly better for plasma (kappa
      = 0. 68) than for leukocytes (kappa = 0.53), due to a greater proportion of
      patients with detectable viral loads in leukocytes having negative blood
      cultures.

PMID- 10203502
TI  - Latent Pneumocystis carinii infection in commercial rat colonies: comparison of
      inductive immunosuppressants plus histopathology, PCR, and serology as detection
      methods.
AB  - Histopathologic evaluation combined with a period of immunosuppression has been
      the standard procedure for detection of Pneumocystis carinii in commercial rat
      colonies. Variation in induction regimens and in the sensitivity of detection
      methods may result in underreporting of the presence of P. carinii in breeding
      colonies or delay its detection. In the present study, methylprednisolone and
      cyclophosphamide were evaluated for the ability to induce P. carinii infection in
      rats from an enzootically infected commercial barrier colony. The presence of P.
      carinii was detected by histopathologic methods and by amplification of a
      targeted region of the P. carinii thymidylate synthase gene by PCR over the 8
      week study period. Sera taken from rats prior to either induction regimen were
      evaluated for the presence of P. carinii-specific antibodies by the
      immunoblotting technique. Few significant differences in ability to induce
      organism burden or in histopathology were observed between the two
      immunosuppressive regimens. However, a dramatic loss of weight over the study
      period was observed in rats treated with methylprednisolone but not in rats
      treated with cyclophosphamide. Although histopathologic changes attributable to
      P. carinii did not appear before 2 weeks with either immunosuppressant, the
      presence of the organism in these animals was detected by immunoblotting and PCR.
      Cyst scores and the intensities of the histopathologic lesions increased during
      the study period, but the number of rats exhibiting evidence of P. carinii
      infection did not change after week 3. These results suggest that use of the PCR
      method on postmortem lung tissue of rats without prior induction regimens or
      identification of anti-P. carinii antibodies in antemortem serum samples is a
      sufficiently sensitive method for detection of the presence of a P. carinii
      carrier state in rodent breeding colonies.

PMID- 10203501
TI  - Comparison of direct plating and broth enrichment culture for the detection of
      intestinal colonization by glycopeptide-resistant enterococci among hospitalized
      patients.
AB  - The results of prevalence studies on glycopeptide-resistant enterococci (GRE) in
      the intestine may be influenced by the detection methods applied. In most studies
      different media, different concentrations of antibiotics, and different methods
      are used, and these differences result in differences in recovery rates. In this
      cross-sectional study on the carrier state of GRE among patients at the
      University Hospital Antwerp, Antwerp, Belgium, performed on 21 May 1996, direct
      plating and broth enrichment were compared by using the same media. Stool samples
      (n = 213) or rectal swabs (n = 122) were plated directly on Enterococcosel agar
      (bioMerieux) and after enrichment in Enterococcosel broth. The prevalence of GRE
      was 12.8%. Direct plating recovered 53.4% of the GRE isolates, and broth
      enrichment recovered an additional 46.5% of them; in the latter test the isolates
      were thus present at less than 10(3) CFU per g of feces. The prevalence of GRE
      among dialysis patients was higher than among the other patients, but the
      difference was not significant (P = 0.06), possibly as a result of the small
      numbers of dialysis patients examined. The GRE species isolated included 19 E.
      gallinarum (44.2%), 13 E. faecium (30.2%), 6 E. faecalis (13.9%), and 5 E.
      casseliflavus (11.6%) isolates. All E. faecalis and E. faecium strains isolated
      carried the vanA gene, and E. gallinarum and E. casseliflavus carried the vanC1
      and vanC2 gene, respectively. The majority of isolates were polyclonal. Our data
      indicate that the rate of detection of GRE from both stool samples and rectal
      swabs is significantly increased with enrichment cultures.

PMID- 10203503
TI  - Molecular cloning and characterization of the Ehrlichia chaffeensis variable
      length PCR target: an antigen-expressing gene that exhibits interstrain
      variation.
AB  - A clone expressing an immunoreactive protein with an apparent molecular mass of
      44 kDa was selected from an Ehrlichia chaffeensis Arkansas genomic library by
      probing with anti-E. chaffeensis hyperimmune mouse ascitic fluid. Nucleotide
      sequencing revealed an open reading frame (ORF) capable of encoding a 198-amino
      acid polypeptide. The ORF contained four imperfect, direct, tandem 90-bp repeats.
      The nucleotide and deduced amino acid sequences did not show close homologies to
      entries in the molecular databases. PCR with primers whose sequences matched the
      sequences flanking the ORF was performed with DNA samples extracted from cell
      cultures infected with nine different isolates of E. chaffeensis, blood samples
      from seven patients with monocytic ehrlichiosis, and Amblyomma americanum ticks
      collected in four different states. The resulting amplicons varied in length,
      containing three to six repeat units. This gene, designated the variable-length
      PCR target, is useful for PCR detection of E. chaffeensis and differentiation of
      isolates.

PMID- 10203504
TI  - Mycobacterium malmoense-specific nested PCR based on a conserved sequence
      detected in random amplified polymorphic DNA fingerprints.
AB  - Mycobacterium malmoense is an opportunistic human pathogen of increasing clinical
      importance. Since it is difficult to detect and identify the organism by
      conventional techniques, it was decided to seek a nucleic acid amplification
      method specific for M. malmoense. The method was based on detection of a
      conserved band in random amplified polymorphic DNA (RAPD) fingerprints of 45 M.
      malmoense strains. This band was a 1,046-bp product which was proven to be M.
      malmoense specific in dot blot hybridization analysis with a panel of
      mycobacterial strains belonging to 39 other species. The fragment was sequenced,
      and oligonucleotide primers were synthesized to evaluate the specificity of the
      PCR. Two primer pairs were found to be specific and sensitive in the nested PCR
      that was developed. All 49 M. malmoense strains analyzed produced a PCR product
      of the expected size. In contrast, no strains belonging to the other
      mycobacterial species tested produced amplicons with these primers under
      specified reaction conditions. The results of the electrophoresis were confirmed
      by the hybridization with the M. malmoense-specific oligonucleotide probe. This
      method could be applied to the analysis of clinical or environmental samples,
      permitting the rapid detection of M. malmoense.

PMID- 10203505
TI  - Methicillin-resistant Staphylococcus aureus outbreak in a veterinary teaching
      hospital: potential human-to-animal transmission.
AB  - During a 13-month period, 11 equine patients visiting a veterinary teaching
      hospital for various diagnostic and surgical procedures developed postprocedural
      infections from which methicillin (oxacillin)-resistant Staphylococcus aureus
      (MRSA) strains were isolated. The S. aureus isolates were identified by
      conventional methods that included Gram staining, tests for colonial morphology,
      tests for clumping factor, and tests for coagulase and urease activities and were
      also tested with the API STAPH IDENT system. Antimicrobial susceptibility tests
      were performed by the disk diffusion method. The biochemical profile and
      antibiogram of each isolate suggested that the isolates may have come from a
      common source. Because MRSA strains are very uncommon animal isolates but are
      rather common human isolates, a nasal swab specimen for culture was collected
      voluntarily from five persons associated with equine surgery and recovery in an
      attempt to identify a possible source of the organisms. MRSA strains were
      isolated from three of the five people, with one person found to be colonized
      with two biotypes of MRSA. The MRSA isolates from the people appeared to be
      identical to the isolates from horses. Further study of the isolates included
      SmaI and EagI macrorestriction analysis by pulsed-field gel electrophoresis
      conducted in two different laboratories. The results indicated that both the
      equine and human isolates were members of a very closely related group which
      appear to have originated from a common source. On the basis of the pattern
      associated with the infection, it is speculated that the members of the
      Veterinary Teaching Hospital staff were the primary source of the infection,
      although the specific mode of transmission is unclear.

PMID- 10203506
TI  - Coaggregation of Candida dubliniensis with Fusobacterium nucleatum.
AB  - The binding of microorganisms to each other and oral surfaces contributes to the
      progression of microbial infections in the oral cavity. Candida dubliniensis, a
      newly characterized species, has been identified in human immunodeficiency virus
      seropositive patients and other immunocompromised individuals. C. dubliniensis
      phenotypically resembles Candida albicans in many respects yet can be identified
      and differentiated as a unique Candida species by phenotypic and genetic
      profiles. The purpose of this study was to determine oral coaggregation (CoAg)
      partners of C. dubliniensis and to compare these findings with CoAg of C.
      albicans under the same environmental conditions. Fifteen isolates of C.
      dubliniensis and 40 isolates of C. albicans were tested for their ability to
      coaggregate with strains of Fusobacterium nucleatum, Peptostreptococcus micros,
      Peptostreptococcus magnus, Peptostreptococcus anaerobius, Porphyromonas
      gingivalis, and Prevotella intermedia. When C. dubliniensis and C. albicans
      strains were grown at 37 degrees C on Sabouraud dextrose agar, only C.
      dubliniensis strains coaggregated with F. nucleatum ATCC 49256 and no C. albicans
      strains showed CoAg. However, when the C. dubliniensis and C. albicans strains
      were grown at 25 or 45 degrees C, both C. dubliniensis and C. albicans strains
      demonstrated CoAg with F. nucleatum. Heating the C. albicans strains (grown at 37
      degrees C) at 85 degrees C for 30 min or treating them with dithiothreitol
      allowed the C. albicans strains grown at 37 degrees C to coaggregate with F.
      nucleatum. CoAg at all growth temperatures was inhibited by mannose and alpha
      methyl mannoside but not by EDTA or arginine. The CoAg reaction between F.
      nucleatum and the Candida species involved a heat-labile component on F.
      nucleatum and a mannan-containing heat-stable receptor on the Candida species.
      The CoAg reactions between F. nucleatum and the Candida species may be important
      in the colonization of the yeast in the oral cavity, and the CoAg of C.
      dubliniensis by F. nucleatum when grown at 37 degrees C provides a rapid,
      specific, and inexpensive means to differentiate C. dubliniensis from C. albicans
      isolates in the clinical laboratory.

PMID- 10203507
TI  - Detection of unculturable bacteria in periodontal health and disease by PCR.
AB  - Recently developed molecular methods have made it possible to characterize mixed
      microflora in their entirety, including the substantial numbers of bacteria which
      do not grow on artificial culture media. In a previous study, molecular analysis
      of the microflora associated with acute oral infections resulted in the
      identification of three phylotypes, PUS3.42, PUS9.170, and PUS9.180, representing
      as-yet-uncultured organisms. The aim of this study was to design and validate
      specific PCR primers for these phylotypes and to determine their incidences in
      samples collected from healthy and diseased periodontal tissues. Two specific
      reverse primers were devised for each phylotype, and these were used in duplex
      PCRs with universal forward and reverse primers. All three phylotypes were
      detected in periodontal sites; PUS9.170, related to oral asaccharolytic
      Eubacterium spp., was significantly associated with disease. This study
      demonstrates the possibility of using unculturable, and therefore
      uncharacterized, organisms as markers of disease.

PMID- 10203509
TI  - Comparison of E-test and broth microdilution methods for antifungal drug
      susceptibility testing of molds.
AB  - We compared the E test with a broth microdilution method, performed according to
      National Committee for Clinical Laboratory Standards document M27-A guidelines,
      for determining the in vitro susceptibilities of 90 isolates of pathogenic molds
      (10 Absidia corymbifera, 10 Aspergillus flavus, 10 Aspergillus fumigatus, 10
      Aspergillus niger, 10 Aspergillus terreus, 10 Exophiala dermatitidis, 10 Fusarium
      solani, 10 Scedosporium apiospermum, 5 Scedosporium prolificans, and 5
      Scopulariopsis brevicaulis). Overall, there was 71% agreement between the results
      of the two methods for amphotericin B (E-test MICs within +/-2 log2 dilutions of
      broth microdilution MICs) and 88% agreement with the results for itraconazole.
      The overall levels of agreement (within +/-2 log2 dilutions) were >/=80% for 5 of
      the 10 species tested against amphotericin B and 8 of the 10 species tested
      against itraconazole. The best agreement between the results was seen with A.
      fumigatus and A. terreus (100% of results for both agents within +/-2 log2
      dilutions). The poorest agreement was seen with S. apiospermum, S. prolificans,
      and S. brevicaulis tested against amphotericin B (20% of results within +/-2 log2
      dilutions). In every instance, this low level of agreement was due to isolates
      for which the broth microdilution MICs were low but for which the E-test MICs
      were much higher. The E test appears to be a suitable alternative procedure for
      testing the susceptibility of Aspergillus spp. and some other molds to
      amphotericin B or itraconazole.

PMID- 10203508
TI  - Western immunoblot analysis of the antigens of Haemobartonella felis with sera
      from experimentally infected cats.
AB  - Cats were experimentally infected with a Florida isolate of Haemobartonella felis
      in order to collect organisms and evaluate the immune response to H. felis.
      Cryopreserved organisms were thawed and injected intravenously into
      nonsplenectomized and splenectomized cats. Splenectomized animals were given 10
      mg of methylprednisolone per ml at the time of inoculation. Blood films were
      evaluated daily for 1 week prior to infection and for up to 60 days postinfection
      (p. i.). Blood for H. felis purification was repeatedly collected from
      splenectomized animals at periods of peak parasitemias. Organisms were purified
      from infected blood by differential centrifugation, separated by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis, and transferred to nitrocellulose
      membranes for immunoblot analysis. Serum was collected from nonsplenectomized
      animals prior to and for up to 60 days p.i. and was used on immunoblots to
      identify antigens. The combination of splenectomy and corticosteroid treatment
      resulted in marked, cyclic parasitemias without concurrent severe anemia,
      providing an opportunity to harvest organisms in a manner that was not lethal to
      the animals. Several antigens (150, 52, 47, 45, and 14 kDa) were identified. An
      antigen with a molecular mass of approximately 14 kDa appeared to be one of the
      most immunodominant and was consistently recognized by immune sera collected at
      various times during the course of infection. These data suggest that one or more
      of these antigens might be useful for the serologic diagnosis of H. felis
      infections in cats.

PMID- 10203510
TI  - Characterization of group C rotaviruses associated with diarrhea outbreaks in
      feeder pigs.
AB  - Feces and serum specimens were collected from three farms in Michigan on which
      approximately 50-lb (8- to 9-week-old) pigs experienced diarrhea just after
      placement into all-in-all-out finishing barns. The clinical signs (profuse watery
      diarrhea lasting about 2 weeks and no vomiting) were similar on all farms, and
      the morbidity rate was high (ranging from 60 to 80%) but without mortality.
      Eleven diarrheic fecal samples from the farms were tested for group A and C
      rotaviruses by immune electron microscopy (IEM) and various assays. IEM indicated
      that the fecal samples reacted only with antiserum against group C rotaviruses,
      and polyacrylamide gel electrophoresis indicated that the samples had
      characteristic genomic electropherotypes for group C rotavirus. Group C rotavirus
      was detected by cell culture immunofluorescence (CCIF) tests in nine fecal
      samples, but no group A rotavirus was detected by enzyme-linked immunosorbent
      assay or CCIF. By reverse transcription (RT)-PCR, all 11 fecal samples were
      positive for group C rotaviruses, with only 2 samples positive for group A
      rotaviruses. However, a second amplification of RT-PCR products using nested
      primers detected group A rotaviruses in all samples. Analysis of nucleotide and
      deduced amino acid sequences of the RT-PCR product (partial-length VP7) of the
      group C rotavirus showed 87.2 to 91% nucleotide identity and 92.6 to 95.9% amino
      acid identity among two strong samples from the different farms and the Cowden
      strain of porcine group C rotavirus. All nine convalescent-phase serum samples
      tested had neutralizing antibodies to the Cowden strain, and the majority of them
      had neutralizing antibody against group A rotaviruses (OSU or/and Gottfried
      strains) by fluorescent focus neutralization tests. Although group C rotaviruses
      have been reported as a cause of sporadic diarrhea in suckling or weanling pigs,
      to our knowledge, this is the first report of epidemic diarrhea outbreaks
      associated with group C rotavirus in older pigs.

PMID- 10203512
TI  - Membrane filtration test for rapid presumptive differentiation of four Candida
      species.
AB  - A rapid enzymatic two-step test for the presumptive differentiation of four
      Candida species commonly occurring in various clinical samples is described. The
      technique involves membrane filtration of a liquid sample, followed by
      preincubation of the membrane filter on Sabouraud glucose agar supplemented with
      ticarcillin-clavulanic acid to yield microcolonies. In a separate assay step,
      parts of the filter are placed on absorbent pads impregnated with fluorogenic 4
      methylumbelliferyl (4-MU) enzyme substrates (4-MU-N-acetyl-beta-D
      galactosaminide, 4-MU-phosphate, 4-MU-pyrophosphate, and 4-MU-beta-D-galactoside)
      in combination with 0.1% digitonin acting as a membrane permeabilizer. The
      membrane filter in contact with the assay medium is incubated to allow cleavage
      of the enzyme substrate, resulting in fluorescent microcolonies under long
      wavelength UV light. This approach, tested on 301 clinical samples, is able to
      presumptively differentiate C. albicans, C. glabrata, C. krusei, and C.
      tropicalis and to distinguish them from other Candida spp. in about 9 to 11 h.
      Overall agreement with the conventional methods of 94.4% (one Candida species
      present in the sample) to 83.8% (multiple Candida spp. present) was obtained. The
      false-negative rates with reference to identification by traditional methods were
      1.3% (single species) and 3.8% (multiple species).

PMID- 10203511
TI  - A highly sensitive assay for detection and quantitation of human cytomegalovirus
      DNA in serum and plasma by PCR and electrochemiluminescence.
AB  - We describe a diagnostic PCR assay (D-PCR) and a quantitative PCR assay (Q-PCR)
      for the detection of human cytomegalovirus (CMV) in plasma and serum. In the D
      PCR, DNA was purified from plasma or serum together with internal control (IC)
      DNA, which monitored both DNA extraction efficiency and PCR efficiency. DNA was
      subjected to PCR with a single primer pair, and the amount of PCR products was
      determined by electrochemiluminescence (ECL) in the QPCR System 5000 (Perkin
      Elmer) after hybridization with Tris (2,2'-bipyridine) ruthenium (II) chelate
      labeled probes. The lower limit of sensitivity of the D-PCR was reached at about
      25 CMV particles/ml. Even with extremely low DNA inputs (four molecules of IC
      DNA/200 microl of plasma), very high yields (near 100%) were reached. DNA
      extracted from specimens that were CMV positive by the D-PCR was subsequently
      used in the Q-PCR, which was similar to the D-PCR. The viral load was calculated
      directly from the ratio of CMV and IC signals obtained by ECL. The Q-PCR assay is
      quantitative in the range of 100 to 150,000 copies of CMV/ml, independent of the
      anticoagulant. Interassay variation, intra-assay variation, and interspecimen
      variation were about 25%, suggesting that the Q-PCR will reliably detect fourfold
      differences in viral load. Comparison of paired serum and plasma specimens from
      CMV-infected individuals showed that serum CMV loads were frequently more than 10
      fold lower than plasma CMV loads.

PMID- 10203513
TI  - Direct quantification of the enteric bacterium Oxalobacter formigenes in human
      fecal samples by quantitative competitive-template PCR.
AB  - Homeostasis of oxalic acid appears to be regulated, in part, by the gut
      associated bacterium Oxalobacter formigenes. The loss of this bacterium from the
      gut flora is associated with an increased susceptibility to hyperoxaluria, a
      condition which can lead to the formation of calcium oxalate crystalluria and
      kidney stones. In order to identify and quantify the presence of O. formigenes in
      clinical specimens, a quantitative-PCR-based assay system utilizing a competitive
      DNA template as an internal standard was developed. This quantitative competitive
      template PCR test allows for the rapid, highly specific, and reproducible
      quantification of O. formigenes in fecal samples and provides a prototype for
      development of DNA-based quantitative assays for enteric bacteria.

PMID- 10203515
TI  - Mycoplasma penetrans and other mycoplasmas in urine of human immunodeficiency
      virus-positive children.
AB  - Urine samples from children with human immunodeficiency virus (HIV) infection and
      healthy controls were examined for mycoplasmas by culture. Standard biochemical
      assays, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and PCR (16S
      and 16S-23S spacer rRNA region) were used for identification of isolates.
      Mycoplasmas were identified from 13 (87%) of 15 HIV-positive patients and 3 (20%)
      of 15 HIV-negative control patients. The frequency and type of mycoplasma varied
      with the severity of HIV infection. Mycoplasma penetrans, Mycoplasma pirum,
      Mycoplasma fermentans, and Mycoplasma genitalium were isolated from patients with
      severe immunodeficiency. Mycoplasma hominis and Ureaplasma urealyticum were
      isolated more frequently from children in the early stages of HIV infection and
      from HIV-negative patients. Mycoplasma penetrans was isolated from one (50%) of
      two patients in Centers for Disease Control and Prevention (CDC) group B and from
      five (55.5%) of nine pediatric patients with AIDS (CDC group C). This is the
      first report that indicates that "AIDS-associated" mycoplasmas are more common in
      HIV-infected children than in HIV-negative controls.

PMID- 10203514
TI  - New enzyme immunoassays for sensitive detection of circulating Candida albicans
      mannan and antimannan antibodies: useful combined test for diagnosis of systemic
      candidiasis.
AB  - Two standardized enzyme immunoassays for the serological diagnosis of candidiasis
      were developed. The first one detects antimannan antibodies, while the second one
      detects mannan with a sensitivity of 0.1 ng/ml. These tests were applied to 162
      serum samples retrospectively selected from 43 patients with mycologically and
      clinically proven candidiasis caused by Candida albicans. Forty-three serum
      samples were positive for mannan, and 63 had significant antibody levels.
      Strikingly, only five serum samples were simultaneously positive by both tests.
      When the results were analyzed per patient, 36 (84%) presented at least one serum
      positive by one test. For 30 of them, positivity by one test was always
      associated with negative results by the other test for any of the tested sera.
      For six patients whose sera were positive for either an antigen or an antibody
      response, a balance between positivity by each test was evidenced by kinetic
      analysis of sera drawn during the time course of the infection. Controls
      consisted of 98 serum samples from healthy individuals, 93 serum samples from
      patients hospitalized in intensive care units, and 39 serum samples from patients
      with deep mycoses. The sensitivities and specificities were 40 and 98% and 53 and
      94% for mannanemia or antibody detection, respectively. These values reached 80
      and 93%, respectively, when the results of both tests were combined. These
      observations, which clearly demonstrate a disparity between circulation of a
      given mannan catabolite and antimannan antibody response, suggest that use of
      both enzyme immunoassays may be useful for the routine diagnosis of candidiasis.

PMID- 10203516
TI  - Pulsed-field gel electrophoresis used to investigate genetic diversity of
      Haemophilus influenzae type b isolates in Australia shows differences between
      Aboriginal and non-Aboriginal isolates.
AB  - We used pulsed-field gel electrophoresis to study the epidemiology and population
      structure of Haemophilus influenzae type b. DNAs from 187 isolates recovered
      between 1985 and 1993 from Aboriginal children (n = 76), non-Aboriginal children
      (n = 106), and non-Aboriginal adults (n = 5) in urban and rural regions across
      Australia were digested with the SmaI restriction endonuclease. Patterns of 13 to
      17 well-resolved fragments (size range, approximately 8 to 500 kb) defining 67
      restriction fragment length polymorphism (RFLP) types were found. Two types
      predominated. One type (n = 37) accounted for 35 (46%) of the isolates from
      Aboriginals and 2 (2%) of the isolates from non-Aboriginals, and the other type
      (n = 41) accounted for 2 (3%) of the isolates from Aboriginals and 39 (35%) of
      the isolates from non-Aboriginals. Clustering revealed seven groups at a genetic
      distance of approximately 50% similarity in a tree-like dendrogram. They included
      two highly divergent groups representing 50 (66%) isolates from Aboriginals and 6
      (5%) isolates from non-Aboriginals and another genetically distinct group
      representing 7 (9%) isolates from Aboriginals and 81 (73%) isolates from non
      Aboriginals. The results showed a heterogeneous clonal population structure, with
      the isolates of two types accounting for 42% of the sample. There was no
      association between RFLP type and the diagnosis of meningitis or epiglottitis,
      age, sex, date of collection, or geographic location, but there was a strong
      association between the origin of isolates from Aboriginal children and RFLP type
      F2a and the origin of isolates from non-Aboriginal children and RFLP type A8b.
      The methodology discriminated well among the isolates (D = 0.91) and will be
      useful for the monitoring of postvaccine isolates of H. influenzae type b.

PMID- 10203517
TI  - Femur osteomyelitis due to a mixed fungal infection in a previously healthy man.
AB  - We describe a previously healthy, 22-year-old man who, after a closed fracture of
      the femur and subsequent operation, developed chronic osteomyelitis. Within a few
      days, infected bone fragments, bone, and wound drainage repeatedly yielded three
      different filamentous fungi: Aspergillus fumigatus, Aspergillus flavus, and
      Chalara ellisii. Histologic examination of the bone revealed septate hyphae.
      After sequential necrotomies of the femur and irrigation-suction drainage with
      added antimycotic therapy, the infection ceased and the fracture healed. This
      case is unique in that it is the only known instance in which a long bone was
      affected in an immunocompetent individual, with no evidence of any systemic
      infection, by a mixed population of two different Aspergillus spp. and the rare
      filamentous fungus C. ellisii. Environmental factors that could potentiate the
      infection include blood and edema fluid resulting from the surgical procedure and
      the presence of the osteosynthetic plate.

PMID- 10203518
TI  - Clinical and pathologic evaluation of chronic Bartonella henselae or Bartonella
      clarridgeiae infection in cats.
AB  - Human Bartonella infections result in diverse medical presentations, whereas many
      cats appear to tolerate chronic bacteremia without obvious clinical
      abnormalities. Eighteen specific-pathogen-free cats were inoculated with
      Bartonella henselae- and/or Bartonella clarridgeiae-infected cat blood and
      monitored for 454 days. Relapsing bacteremia did not correlate with changes in
      protein profiles or differences in antigenic protein recognition. Intradermal
      skin testing did not induce a delayed type hypersensitivity reaction to cat
      scratch disease skin test antigen. Thirteen cats were euthanatized at the end of
      the study. Despite persistent infection, clinical signs were minimal and gross
      necropsy results were unremarkable. Histopathology revealed peripheral lymph node
      hyperplasia (in all of the 13 cats), splenic follicular hyperplasia (in 9 cats),
      lymphocytic cholangitis/pericholangitis (in 9 cats), lymphocytic hepatitis (in 6
      cats), lymphoplasmacytic myocarditis (in 8 cats), and interstitial lymphocytic
      nephritis (in 4 cats). Structures suggestive of Bartonella were visualized in
      some Warthin-Starry stained sections, and Bartonella DNA was amplified from the
      lymph node (from 6 of the 13 cats), liver (from 11 cats) heart (from 8 cats),
      kidney (from 9 cats), lung (from 2 cats), and brain (from 9 cats). This study
      indicates that B. henselae or B. clarridgeiae can induce chronic infection
      following blood transfusion in specific-pathogen-free cats and that Bartonella
      DNA can be detected in blood, brain, lymph node, myocardium, liver, and kidney
      tissues of both blood culture-positive cats and blood culture-negative cats.
      Detection of histologic changes in these cats supports a potential etiologic role
      for Bartonella species in several idiopathic disease processes in cats.

PMID- 10203520
TI  - Evaluation of recombinant antigens for serodiagnosis of Chagas' disease in South
      and Central America.
AB  - The commercially available diagnostic tests for Chagas' disease employ whole
      extracts or semipurified fractions of Trypanosoma cruzi epimastigotes.
      Considerable variation in the reproducibility and reliability of these tests has
      been reported by different research laboratories, mainly due to cross-reactivity
      with other pathogens and standardization of the reagents. The use of recombinant
      antigens for the serodiagnosis of Chagas' disease is recommended to increase the
      sensitivity and specificity of serological tests. Expressed in Escherichia coli,
      as fusion products with glutathione S-transferase, six T. cruzi recombinant
      antigens (H49, JL7, A13, B13, JL8, and 1F8) were evaluated in an enzyme-linked
      immunosorbent assay for Chagas' disease. The study was carried out with a panel
      of 541 serum samples of chagasic and nonchagasic patients from nine countries of
      Latin America (Argentina, Bolivia, Brazil, Chile, Colombia, El Salvador,
      Guatemala, Honduras, and Venezuela). The optimal concentration of each
      recombinant antigen for coating of plates was determined with the help of 125I
      labelled recombinant proteins. While the specificity of the epimastigote antigen
      was 84% because of false positives from leishmaniasis cases, for the recombinant
      antigens it varied from 96.2 to 99.6%. Recombinant antigens reacted with 79 to
      100% of serum samples from chronic chagasic patients. In this way, it is proposed
      that a mixture of a few T. cruzi recombinant antigens should be employed in a
      diagnostic kit to minimize individual variation and promote high sensitivity in
      the diagnosis of Chagas' disease.

PMID- 10203519
TI  - Detection of enzootic babesiosis in baboons (Papio cynocephalus) and phylogenetic
      evidence supporting synonymy of the genera Entopolypoides and Babesia.
AB  - Blood smear evaluation of two baboons (Papio cynocephalus) experiencing acute
      hemolytic crises following experimental stem cell transplantation revealed
      numerous intraerythrocytic organisms typical of the genus Babesia. Both animals
      had received whole-blood transfusions from two baboon donors, one of which was
      subsequently found to display rare trophozoites of Entopolypoides macaci. An
      investigation was then undertaken to determine the prevalence of hematozoa in
      baboons held in our primate colony and to determine the relationship, if any,
      between the involved species. Analysis of thick and thin blood films from 65
      healthy baboons (23 originating from our breeding facility, 26 originating from
      an out-of-state breeding facility, and 16 imported from Africa) for hematozoa
      revealed rare E. macaci parasites in 31%, with respective prevalences of 39, 35,
      and 12%. Phylogenetic analysis of nuclear small-subunit rRNA gene sequences
      amplified from peripheral blood of a baboon chronically infected with E. macaci
      demonstrated this parasite to be most closely related to Babesia microti (97.9%
      sequence similarity); sera from infected animals did not react in indirect
      fluorescent-antibody tests with Babesia microti antigen, however, suggesting that
      they represent different species. These results support an emerging view that the
      genus Entopolypoides Mayer 1933 is synonymous with that of the genus Babesia
      Starcovici 1893 and that the morphological variation noted among intracellular
      forms is a function of alteration in host immune status. The presence of an
      underrecognized, but highly enzootic, Babesia sp. in baboons may result in
      substantial, unanticipated impact on research programs. The similarity of this
      parasite to the known human pathogen B. microti may also pose risks to humans
      undergoing xenotransplantation, mandating effective screening of donor animals.

PMID- 10203521
TI  - Visualization of hydatid elements: comparison of several techniques.
AB  - Some techniques available at our laboratory were tested for their ability to aid
      in the morphological diagnosis of hydatid elements (Echinococcus granulosus
      ["Taenia echinococcus"]) isolated from cysts in humans and sheep. Unstained,
      methanol-fixed hooklets were fluorescent, most starkly so under violet light
      (excitation filter wavelength, 405 nm; long-pass filter wavelength, 495 nm).
      Auramine-rhodamine and Gram procedures failed to stain hooklets. Ziehl-Neelsen
      stain yielded indifferent results when organisms were viewed under transmitted
      light but resulted in a surprisingly intense red fluorescence when organisms were
      viewed under green light (excitation, 546 nm; long pass, 590 nm). Wheatley
      trichrome stain gave better and more uniform results than fuchsin. Ryan trichrome
      blue stain was the best under transmitted light; hooklets stained uniformly and
      intensely and were easily distinguishable from the background. Very satisfactory
      results were also obtained with a much simpler procedure (modified Baxby
      technique: no fixation, steaming hot 1% safranin for 2 min, and malachite green
      for 30 s). Therefore, Ryan and modified Baxby stains are recommended for the
      examination of E. granulosus under transmitted light. For fluorescence
      microscopy, Ziehl-Neelsen stain under green excitation light, or violet light
      with no staining, is also very useful. Epifluorescence microscopy is especially
      convenient for examining samples concentrated by filtration, as it renders the
      filter pores inconspicuous.

PMID- 10203522
TI  - Abiotrophia species as a cause of endophthalmitis following cataract extraction.
AB  - Microorganisms of the genus Abiotrophia, members of the oral flora, are known as
      important causes of bacterial endocarditis. In this study, we report two
      individual cases of acute vitreous infection caused by Abiotrophia adiacens and
      Abiotrophia defectiva approximately a week after cataract extraction. Abiotrophia
      isolates were recovered by cultivation of vitreous humor on chocolate agar and
      identified via conventional and API 20 Strep identification systems. An 83-year
      old male patient (A) and an 80-year-old female patient (B) demonstrated almost
      identical symptoms of infectious endophthalmitis manifested as hypopyon and
      opaque media. The vision of both patients was reduced to detection of hand motion
      in the left and the right eyes, respectively. An emergency pars plana core
      vitrectomy was performed, and intraocular antibiotics were administered to each
      patient, who presented 8 months apart in two different institutions. Patients A
      and B were treated with an intravitreal injection of vancomycin-amikacin and
      vancomycin-ceftazidime, respectively, which resulted in complete recovery.

PMID- 10203523
TI  - Second generation of the automated Cobas Amplicor HCV assay improves sensitivity
      of hepatitis C virus RNA detection and yields results that are more clinically
      relevant.
AB  - The first and second generations of the Cobas Amplicor HCV assay were compared
      among patients at risk of hepatitis C virus (HCV) infection. The second
      generation test was found to be of greater sensitivity and of good specificity
      among clinical specimens containing HCV RNA of different genotypes. Finally, this
      new test is shown to predict the outcome of interferon therapy better.

PMID- 10203524
TI  - Virulence factors and phenotypical traits of verotoxin-producing Escherichia coli
      strains isolated from asymptomatic human carriers.
AB  - Fourteen verotoxin-producing Escherichia coli strains isolated from stool samples
      of 14 different asymptomatic human carriers were further characterized. A variety
      of serotypes was found, but none of the strains belonged to serogroup O157. Only
      one isolate carried most of the virulence genes that are associated with
      increased pathogenicity.

PMID- 10203525
TI  - Isolation of Malassezia furfur from a cat.
AB  - During a survey of the occurrence of Malassezia species in the external ear
      canals of cats without otitis externa, Malassezia furfur was isolated. This is
      the first report of the isolation of M. furfur from cats.

PMID- 10203526
TI  - Molecular cloning and sequencing of the aroA gene from Actinobacillus
      pleuropneumoniae and its use in a PCR assay for rapid identification.
AB  - The gene (aroA) of Actinobacillus pleuropneumoniae, serotype 2, encoding 5
      enolpyruvylshikimate-3-phosphate synthase was cloned by complementation of the
      aroA mutation in Escherichia coli K-12 strain AB2829, and the nucleotide sequence
      was determined. A pair of primers from the 5' and 3' termini were selected to be
      the basis for development of a specific PCR assay. A DNA fragment of 1,025 bp was
      amplified from lysed A. pleuropneumoniae serotypes 1 to 12 of biovar 1 or from
      isolated DNA. No PCR products were detected when chromosomal DNAs from other
      genera were used as target DNAs; however, a 1,025-bp DNA fragment was amplified
      when Actinobacillus equuli chromosomal DNA was used as a target, which could be
      easily differentiated by its NAD independence. The PCR assay developed was very
      sensitive, with lower detection limits of 12 CFU with A. pleuropneumoniae cells
      and 0.8 pg with extracted DNA. Specificity and sensitivity make this PCR assay a
      useful method for the rapid identification and diagnosis of A. pleuropneumoniae
      infections.

PMID- 10203527
TI  - Evaluation of the digene hybrid capture II CT-ID test for detection of Chlamydia
      trachomatis in endocervical specimens.
AB  - The performance characteristics of the new signal amplification-based Hybrid
      Capture (HC) II CT-ID test system (Digene, Silver Spring, Md.) with endocervical
      specimens were compared to those of tissue culture and PCR (AMPLICOR CT PCR;
      Roche Molecular Systems, Branchburg, N.J.) for detection of Chlamydia trachomatis
      in 587 women. HC II CT-ID identified 62 of 65 confirmed C. trachomatis-positive
      patients (sensitivity of 95.4%) and was negative for 517 of 522 patients who were
      negative by culture and PCR (specificity of 99.0%). Twelve of the 65 confirmed
      positive patients were negative by culture but were identified by both HC II CT
      ID and PCR (sensitivity of culture was 81.5% [P < 0.01]). In comparison, PCR
      detected 59 of 65 positive specimens (sensitivity of 90.8%) and had a specificity
      of 99.6% (520 of 522). These results demonstrate that the Digene HC II CT-ID test
      is a highly sensitive and specific assay for the detection of C. trachomatis
      infection in endocervical specimens.

PMID- 10203528
TI  - False-positive results obtained with the Alexon ProSpecT Cryptosporidium enzyme
      immunoassay.
AB  - Cryptosporidium is known to cause diarrhea in immunocompromised patients and is
      also associated with outbreaks of disease due to food-borne and waterborne
      parasites. Traditional procedures, involving iodine staining of wet mounts of
      stool sediments and trichrome staining, lack the sensitivity to detect
      Cryptosporidium. Special staining procedures, such as the modified acid-fast and
      safranin stains, are generally employed. Less labor-intensive antigen detection
      assays have simplified detection; however, careful attention to local
      epidemiology is important because false-positive tests occur. Here, we report two
      incidents involving 62 false-positive results obtained with the Alexon ProSpecT
      Cryptosporidium enzyme immunoassay, which were deemed false-positive based on
      negative results obtained from extensive microscopic examinations.

PMID- 10203529
TI  - Microbiological characteristics of yeasts isolated from urinary tracts of
      intensive care unit patients undergoing urinary catheterization.
AB  - We studied 70 intensive care unit patients to determine the incidence of
      nosocomial candiduria associated with indwelling urinary catheters and to assess
      microbiological characteristics of the yeasts. The yeasts were isolated, 13 of 17
      in urine cultures and 4 of 17 in blood cultures, and colonization had occurred 3
      days after the insertion of indwelling urinary catheters. For four strains the
      MICs of the antifungal drugs were high.

PMID- 10203530
TI  - Rapid PCR test for discriminating between Candida albicans and Candida
      dubliniensis isolates using primers derived from the pH-regulated PHR1 and PHR2
      genes of C. albicans.
AB  - The development of a satisfactory means to reliably distinguish between the two
      closely related species Candida albicans and Candida dubliniensis in the clinical
      mycology laboratory has proved difficult because these two species are
      phenotypically so similar. In this study, we have detected homologues of the pH
      regulated C. albicans PHR1 and PHR2 genes in C. dubliniensis. Restriction
      fragment length polymorphism analysis suggests that there are significant
      sequence differences between the genes of the two species. In order to exploit
      this apparent difference, oligonucleotide primers based on the coding sequence of
      the C. albicans PHR1 structural gene were designed and used in PCR experiments.
      Use of these primers with C. albicans template DNA from 17 strains yielded a
      predicted 1.6-kb product, while C. dubliniensis template DNA from 19 strains
      yielded no product. We therefore propose that PCR using these primers is a rapid
      and reliable means of distinguishing the two germ tube- and chlamydospore
      producing species C. albicans and C. dubliniensis.

PMID- 10203531
TI  - Evaluation of MRSA-Screen, a simple anti-PBP 2a slide latex agglutination kit,
      for rapid detection of methicillin resistance in Staphylococcus aureus.
AB  - The MRSA-Screen test (Denka Seiken Co., Ltd., Tokyo, Japan), consisting of a
      slide latex agglutination kit that detects PBP 2a with a monoclonal antibody, was
      blindly compared to the oxacillin disk diffusion test, the oxacillin-salt agar
      screen, and PCR of the mecA gene for the detection of methicillin resistance in
      Staphylococcus aureus. A total of 120 methicillin-susceptible S. aureus (MSSA)
      and 80 methicillin-resistant S. aureus (MRSA) isolates, defined by the absence or
      presence of the mecA gene, respectively, were tested. The MRSA-Screen test, the
      oxacillin disk diffusion test, and the oxacillin-salt agar screening test showed
      sensitivities of 100, 61.3, and 82.5% and specificities of 99.2, 96.7, and 98.3%,
      respectively. We conclude that the MRSA-Screen is a very accurate, reliable, and
      fast test (15 min) for differentiation of MRSA from MSSA colonies on agar plates.

PMID- 10203532
TI  - Comparison of human immunodeficiency virus type 1 (HIV-1) protease mutations in
      HIV-1 genomes detected in plasma and in peripheral blood mononuclear cells from
      patients receiving combination drug therapy.
AB  - Detections of mutations in the protease gene of human immunodeficiency virus type
      1 in plasma and peripheral blood mononuclear cells (PBMC) were sought in two
      matched populations of 23 individuals receiving combination drug therapy with or
      without protease inhibitors. In the control group (23 patients not receiving
      protease inhibitors), no primary resistance mutations were found. In contrast,
      primary resistance mutations (especially at codons M46, V82, and L90) were found
      in 16 of 23 patients (70%) treated with protease inhibitors. In 30% of the cases,
      these mutations were detected in plasma but not in PBMC.

PMID- 10203533
TI  - Detection of caprine herpesvirus 1 in sacral ganglia of latently infected goats
      by PCR.
AB  - A study of the latency of caprine herpesvirus 1 (CpHV.1) was carried out with
      four latently infected goats. Three goats were treated with dexamethasone and
      euthanized after 4 and 6 days. PCR and virus isolation allowed us to detect
      CpHV.1 only in the third and fourth sacral ganglia of the two animals euthanized
      6 days after the start of treatment.

PMID- 10203535
TI  - Use of nucleic acid probes for identification of Mycobacterium tuberculosis
      directly from MB/BacT bottles.
AB  - The feasibility of using nucleic acid probes directly from positive MB/BacT broth
      to identify mycobacteria was determined in this study. A total number of 2,727
      specimens were cultured into the MB/BacT (Organon Teknika) automated system and
      on conventional Loweinstein-Jensen (LJ) slants. The Gen-Probe AccuProbe culture
      identification tests (DNA probes) were used on samples from bottles which were
      identified as positive for mycobacteria by MB/BacT. Samples of positive MB/BacT
      broth (0.1 ml) were used directly in the broth culture method for the DNA probes
      as published by Gen-Probe. Centrifugation of the contents of the bottle was not
      done prior to probe testing. The number of mycobacteria detected by MB/BacT and
      LJ was 253 (221 isolates of M. tuberculosis and 32 isolates of mycobacteria other
      than M. tuberculosis [MOTT]). A total of 96.4% (213 of 221) of the bottles
      growing M. tuberculosis produced a positive direct DNA probe result for M.
      tuberculosis complex. One hundred percent (16 of 16) of the bottles growing M.
      gordonae produced a positive direct DNA probe result for M. gordonae. A total of
      3.6% (8 of 221) of the bottles growing M. tuberculosis did not yield a positive
      direct DNA probe result for M. tuberculosis complex. The testing of subcultures
      made onto solid media from the positive bottles by AccuProbe identified six of
      these eight M. tuberculosis isolates. Two (0.9%) M. tuberculosis isolates gave a
      negative result for the M. tuberculosis probe test applied on the MB/BacT broth
      and its subculture. The rest of the positive MB/BacT bottles growing MOTT (16 of
      32) were negative for M. gordonae, M. avium, M. intracellulare, and M. kansasii
      probes. The sensitivity and specificity of AccuProbe for the identification of M.
      tuberculosis and M. gordonae directly from MB/BacT broth were 96.4 and 100% for
      M. tuberculosis and 100 and 100% for M. gordonae, respectively. The direct
      testing of positive MB/BacT broth by AccuProbe, without prior centrifugation,
      allows for the accurate and rapid identification of M. tuberculosis and M.
      gordonae.

PMID- 10203534
TI  - Evaluation of the MRL diagnostics dengue fever virus IgM capture ELISA and the
      PanBio Rapid Immunochromatographic Test for diagnosis of dengue fever in Jamaica.
AB  - We evaluated two new commercial dengue diagnostic tests, the MRL Diagnostics
      Dengue Fever Virus IgM Capture ELISA and the PanBio Rapid Immunochromatographic
      Test, on serum samples collected during a dengue epidemic in Jamaica. The MRL
      ELISA method correctly identified 98% (78 of 80) of the samples as dengue
      positive, while the PanBio test identified 100% (80 of 80). Both tests were 100%
      (20 samples of 20) specific.

PMID- 10203536
TI  - Invasive aspergillosis caused by Aspergillus ustus: case report and review.
AB  - A case of invasive pulmonary aspergillosis in an allogeneic bone marrow
      transplant recipient caused by Aspergillus ustus is presented. A. ustus was also
      recovered from the hospital environment, which may indicate that the infection
      was nosocomially acquired. A literature review revealed seven cases of invasive
      infections caused by A. ustus, and three of these were primarily cutaneous
      infections. In vitro susceptibility testing of 12 A. ustus isolates showed that
      amphotericin B and terbinafine had fungicidal activity and that itraconazole and
      voriconazole had fungistatic activity.

PMID- 10203537
TI  - First-glance diagnosis of Strongyloides stercoralis autoinfection by stool
      microscopy.
AB  - We report a case of autoinfection due to Strongyloides stercoralis in a 27-year
      old Ethiopian AIDS patient living in Germany for nearly 3 years. This case was
      diagnosed on the basis of a single-view field in microscopy of a freshly obtained
      formalin-fixed stool specimen showing both rhabditiform and filariform larvae.
      The diagnosis of autoinfection by microscopy is discussed in detail.

PMID- 10203538
TI  - Pseudoepidemic of Aspergillus niger infections traced to specimen contamination
      in the microbiology laboratory.
AB  - We report a pseudo-outbreak of Aspergillus niger that followed building
      construction in our clinical microbiology laboratory. Because outbreaks of
      invasive aspergillosis have been linked to hospital construction, strategies to
      minimize dust in patient care areas are common practice. We illustrate that the
      impact of false-positive cultures on patient care should compel laboratories to
      prevent specimen contamination during construction.

PMID- 10203539
TI  - Septicemia caused by dysgonic fermenter 3 in a severely immunocompromised patient
      and isolation of the same microorganism from a stool specimen.
AB  - Dysgonic fermenter 3 (DF-3)-associated bacteremia occurred in a febrile patient
      with acute myelocytic leukemia during aplasia. Another DF-3 isolate, identical by
      ribotyping, was grown 10 weeks later from stool collected in the absence of
      diarrhea. This is the first case in which DF-3 was isolated from blood and stool
      specimens from the same patient.

PMID- 10203540
TI  - Misclassification of susceptible strains of Staphylococcus aureus as methicillin
      resistant S. aureus By a rapid automated susceptibility testing system.
AB  - Eight Staphylococcus aureus strains initially identified by Vitek GPS-BS or GPS
      SA cards as resistant to oxacillin, but susceptible to most non-beta-lactam
      antibiotics, were found on further testing to be susceptible to oxacillin and
      ceftizoxime by disk diffusion tests. For all these strains, the MICs of oxacillin
      were </=0.5 microg/ml by agar dilution tests, and the strains were oxacillin
      susceptible when tested by the BBL Crystal MRSA ID and a Vitek machine with GPS
      101 cards. None grew on oxacillin-salt agar screening plates. None were positive
      for mecA gene sequences by PCR. When S. aureus strains tested by Vitek GPS-SA or
      GPS-BS cards appear resistant to only penicillin and oxacillin, a confirmatory
      test such as the oxacillin-salt agar screening method should be performed.

PMID- 10203541
TI  - Simultaneous detection of Bacteroides forsythus and Prevotella intermedia by 16S
      rRNA gene-directed multiplex PCR.
AB  - In a 16S rRNA gene-directed multiplex PCR, Prevotella intermedia- and Bacteroides
      forsythus-specific reverse primers were combined with a single conserved forward
      primer. A 660-bp fragment and an 840-bp fragment that were specific for both
      species could be amplified simultaneously. A total of 152 clinical samples,
      subgingival plaque and swabs of three different oral mucosae, from 38
      periodontitis patients were used for the evaluation.

PMID- 10203542
TI  - Disk diffusion method for determining susceptibilities of Candida spp. to MK
      0991.
AB  - We have developed an agar-based methodology for testing susceptibilities of
      Candida spp. to the new antifungal agent MK-0991, a glucan synthase inhibitor.
      Results obtained with this method correlated well with the results obtained by
      the National Committee for Clinical Laboratory Standards M27-A broth
      microdilution reference method. However, as noted with prior comparisons of broth
      and agar-based systems, some isolates yielded inhibition zones which were not
      consistent with the MICs obtained for them. Understanding the implications of
      these differences will require testing in an in vivo system.

PMID- 10203543
TI  - Assessment of metronidazole susceptibility in Helicobacter pylori: statistical
      validation and error rate analysis of breakpoints determined by the disk
      diffusion test.
AB  - Metronidazole susceptibility of 100 Helicobacter pylori strains was assessed by
      determining the inhibition zone diameters by disk diffusion test and the MICs by
      agar dilution and PDM Epsilometer test (E test). Linear regression analysis was
      performed, allowing the definition of significant linear relations, and revealed
      correlations of disk diffusion results with both E-test and agar dilution results
      (r2 = 0.88 and 0.81, respectively). No significant differences (P = 0.84) were
      found between MICs defined by E test and those defined by agar dilution, taken as
      a standard. Reproducibility comparison between E-test and disk diffusion tests
      showed that they are equivalent and with good precision. Two interpretative
      susceptibility schemes (with or without an intermediate class) were compared by
      an interpretative error rate analysis method. The susceptibility classification
      scheme that included the intermediate category was retained, and breakpoints were
      assessed for diffusion assay with 5-microg metronidazole disks. Strains with
      inhibition zone diameters less than 16 mm were defined as resistant (MIC > 8
      microg/ml), those with zone diameters equal to or greater than 16 mm but less
      than 21 mm were considered intermediate (4 microg/ml < MIC </= 8 microg/ml), and
      those with zone diameters of 21 mm or greater were regarded as susceptible (MIC
      </= 4 microg/ml). Error rate analysis applied to this classification scheme
      showed occurrence frequencies of 1% for major errors and 7% for minor errors,
      when the results were compared to those obtained by agar dilution. No very major
      errors were detected, suggesting that disk diffusion might be a good alternative
      for determining the metronidazole sensitivity of H. pylori strains.

PMID- 10203544
TI  - Ability of a rapid serology test to detect seroconversion to herpes simplex virus
      type 2 glycoprotein G soon after infection.
AB  - Sera (n = 188) from 29 patients with first-episode genital herpes simplex virus
      type 2 (HSV-2) infections were tested by POCkit-HSV-2 and Western blot (WB) to
      determine the speed of seroconversion. The median time to detection of HSV-2
      antibody was 13 days (range, 3 to 102 days) by the POCkit-HSV-2 test versus 13
      days (range, 2 to 58 days) for WB.

PMID- 10203545
TI  - High prevalence of GB virus C in Brazil and molecular evidence for intrafamilial
      transmission.
AB  - The prevalence of GB virus C (GBV-C) in candidate Brazilian blood donors with
      normal and elevated alanine aminotransferase levels was found to be 5.2% (5 of
      95) and 6.5% (5 of 76), respectively. Among Brazilian patients, GBV-C was found
      in 9.5% (13 of 137) of cases of hepatitis not caused by hepatitis A virus (HAV),
      HBV, HCV, HDV, or HEV (non-A-E hepatitis) and in 18.2% (8 of 44) of individuals
      infected with HCV. Molecular characterization of GBV-C by partial sequencing of
      the NS3 region showed clustering between members of a single family, implying
      intrafamilial transmission. In conclusion, these results together suggest that
      contagion mechanisms which facilitate intrafamilial transmission of GBV-C may
      partially explain the high prevalence of viremic carriers worldwide.

PMID- 10203546
TI  - Survey of antibiotic resistance among enterococci in North Rhine-Westphalia,
      Germany.
AB  - A surveillance study on antibiotic resistance of enterococcal isolates (n = 730)
      was carried out in North Rhine-Westphalia, Germany, in 1997. Resistance rates to
      ampicillin (7.4%), high-level gentamicin (15.0%), high-level streptomycin
      (27.9%), ciprofloxacin (37.9%), vancomycin (1.5%), and teicoplanin (1.5%) were
      determined. All vancomycin-resistant enterococci (VRE) carried the vanA gene.
      SmaI and ApaI macrorestriction patterns indicated an intra- and interhospital
      spread of VRE.

PMID- 10203547
TI  - Genetic diversity among Escherichia coli isolates carrying f18 genes from pigs
      with porcine postweaning diarrhea and edema disease.
AB  - Multilocus enzyme electrophoresis was applied to detect allelic variation and
      multilocus genotypes (electrophoretic types [ETs]) among 43 Escherichia coli
      isolates from weaned pigs suffering from edema disease or from diarrhea. ETs were
      analyzed in relation to O serogroups and virulence genes (sta, stb, lt, stx2, and
      f18) by DNA hybridization. Genomic diversity was the lowest in serogroup O138,
      while virulence genes (stx2 and f18) were the most uniform in serogroup O139. In
      general, the serogroups or toxin and F18 fimbria types were not related to
      selected ETs, suggesting that the toxin and f18 fimbria genes in E. coli isolates
      from pigs with postweaning diarrhea or edema disease occur in a variety of
      chromosomal backgrounds.

PMID- 10203548
TI  - Cytolethal distending toxin genes in Campylobacter jejuni and Campylobacter coli
      isolates: detection and analysis by PCR.
AB  - Campylobacter jejuni produces a toxin called cytolethal distending toxin (CDT).
      Knowledge of the prevalence and homogeneity of Campylobacter sp. cdt genes is
      incomplete. In this work, we identified four PCR primer pairs that collectively
      amplified cdt genes in all of the C. jejuni and Campylobacter coli strains
      tested. Restriction analyses of the cdt PCR products showed clear differences
      between the cdt genes of these two species, yet there were few heterogeneities
      noted between members of the same species. Consequently, it may be possible to
      speciate C. jejuni and C. coli isolates on the basis of restriction patterns
      within their cdt genes.

PMID- 10203549
TI  - Is Helicobacter pylori a factor in coronary atherosclerosis?

PMID- 10203550
TI  - Folate metabolism and requirements.
AB  - Folate functions in multiple coenzyme forms in acceptance, redox processing and
      transfer of one-carbon units, including nucleotides and certain amino acids.
      Folate-requiring metabolic processes are influenced by folate intake, intake of
      other essential nutrients, including vitamins B-12 and B-6, and at least one
      common genetic polymorphism. Estimates of folate requirements have been based on
      intakes associated with maintenance of normal plasma and erythrocyte folate
      concentrations and functional tests that reflect abnormalities in folate
      dependent reactions. Dietary Reference Intakes for folate that have been
      developed recently are based primarily on metabolic studies in which erythrocyte
      folate concentration was considered the major indicator of adequacy. For adults
      >/=19 y, the Recommended Dietary Allowance (RDA) is 400 microg/d of dietary
      folate equivalents (DFE); for lactating and pregnant women, the RDAs include an
      additional 100 and 200 microg of DFE/d, respectively.

PMID- 10203551
TI  - Vitamin A as "anti-infective" therapy, 1920-1940.
AB  - In the last fifteen years, a large series of controlled clinical trials showed
      that vitamin A supplementation reduces morbidity and mortality of children in
      developing countries. It is less well known that vitamin A underwent two decades
      of intense clinical investigation prior to World War II. In the 1920s, a theory
      emerged that vitamin A could be used in "anti-infective" therapy. This idea,
      largely championed by Edward Mellanby, led to a series of at least 30 trials to
      determine whether vitamin A--usually supplied in the form of cod-liver oil--could
      reduce the morbidity and mortality of respiratory disease, measles, puerperal
      sepsis, and other infections. The early studies generally lacked such innovations
      known to the modern controlled clinical trial such as randomization, masking,
      sample size and power calculations, and placebo controls. Results of the early
      trials were mixed, but the pharmaceutical industry emphasized the positive
      results in their advertising to the public. With the advent of the sulfa
      antibiotics for treatment of infections, scientific interest in vitamin A as
      "anti-infective" therapy waned. Recent controlled clinical trials of vitamin A
      from the last 15 y follow a tradition of investigation that began largely in the
      1920s.

PMID- 10203552
TI  - Nitric oxide synthase inhibitor attenuates intestinal damage induced by zinc
      deficiency in rats.
AB  - A nitric oxide synthase (NOS) inhibitor, NG-nitro-L -arginine methyl ester (L
      NAME), was given to zinc-deficient (ZD) rats to determine whether it prevents the
      intestinal damage usually observed under these conditions. Weanling male rats
      were given free access to a ZD diet (2 mg zinc/kg), whereas control rats
      including pair-fed (PF) and ad libitum consumption (AL) groups were given a zinc
      supplemented (50.8 mg zinc/kg) diet for 4 wk. Half of the ZD rats received L-NAME
      (0.3 g/L in drinking water) for 3 wk starting at the wk 2 of the deficient
      period. Plasma zinc concentration in ZD rats was significantly lower (P < 0.05)
      than that of AL and PF rats. Administration of L-NAME did not alter this
      concentration. Intestinal zinc concentration did not differ among groups.
      However, metallothionein-1 (MT-1) mRNA level was significantly lower in the
      intestine of ZD rats than in AL or PF rats. Treatment of ZD rats with L-NAME did
      not affect this level. Intestinal microvascular permeability evaluated by Evans
      blue showed significantly higher extravasation in ZD rats than in AL rats,
      whereas L-NAME administration inhibited the extravasation. Expression of
      inducible NOS mRNA was observed in intestine of ZD but not of AL or PF rats, and
      there was no significant difference between ZD rats, regardless of L-NAME
      treatment. The activity ratio of inducible NOS to total NOS in ZD rats not
      receiving L-NAME was significantly higher than that in AL rats or ZD rats treated
      with L-NAME (P < 0.05). The number of apoptotic-positive and goblet cells in
      intestinal villi was significantly higher in ZD rats compared with AL or PF rats.
      L-NAME administration in ZD rats reversed this effect. These results indicate
      that inhibition of NOS ameliorates zinc deficiency-induced intestinal damage in
      rats.

PMID- 10203553
TI  - Glucocorticoids mediate the enhanced expression of intestinal type II arginase
      and argininosuccinate lyase in postweaning pigs.
AB  - Arginine metabolism is enhanced in the small intestine of weanling pigs, but the
      molecular mechanism(s) involved is not known. The objectives of this study were
      to determine the following: 1) whether glucocorticoids play a role in induction
      of intestinal arginine metabolic enzymes during weaning; 2) whether the induction
      of enzyme activities was due to increases in corresponding mRNA levels; and 3)
      the identity of the arginase isoform(s) expressed in the small intestine. Jejunum
      was obtained from 29-d-old weaned pigs that were or were not treated with 17-beta
      hydroxy-11beta-(4-dimethylaminophenyl)17alpha-(prop- 1-ynyl)es tra-4,9-dien-3-one
      (RU486, an antagonist of glucocorticoid receptors), or from age-matched suckling
      pigs. Activities and mRNA levels for type I and type II arginases,
      argininosuccinate synthase (ASS) and argininosuccinate lyase (ASL) were
      determined. Activities of arginase, ASL and ASS increased by 635, 56 and 106%,
      respectively, in weanling pigs, compared with suckling pigs. RU486 treatment
      attenuated the increase in arginase activity by 74% and completely prevented the
      ASL induction in weanling pigs, but had no effect on ASS activity. Pig intestine
      expresses both type I and type II arginases. On the basis of immunoblot analyses,
      there was no significant difference in levels of intestinal type I arginase among
      these three groups of pigs, indicating that changes in arginase activity were due
      only to type II arginase. The mRNA levels for type II arginase and ASL increased
      by 135 and 198%, respectively, in weanling pigs compared with suckling pigs, and
      this induction was completely prevented by RU486. In contrast, ASS mRNA levels
      did not differ between suckling and weanling pigs. These results suggest that
      intestinal type II arginase, ASS and ASL are regulated differentially at
      transcriptional and post-translational levels and that glucocorticoids play a
      major role in the induction of type II arginase and ASL mRNAs in the small
      intestine of weanling pigs.

PMID- 10203554
TI  - Apoptosis and cell-cycle arrest in human and murine tumor cells are initiated by
      isoprenoids.
AB  - Diverse classes of phytochemicals initiate biological responses that effectively
      lower cancer risk. One class of phytochemicals, broadly defined as pure and mixed
      isoprenoids, encompasses an estimated 22,000 individual components. A
      representative mixed isoprenoid, gamma-tocotrienol, suppresses the growth of
      murine B16(F10) melanoma cells, and with greater potency, the growth of human
      breast adenocarcinoma (MCF-7) and human leukemic (HL-60) cells. beta-Ionone, a
      pure isoprenoid, suppresses the growth of B16 cells and with greater potency, the
      growth of MCF-7, HL-60 and human colon adenocarcinoma (Caco-2) cells. Results
      obtained with diverse cell lines differing in ras and p53 status showed that the
      isoprenoid-mediated suppression of growth is independent of mutated ras and p53
      functions. beta-Ionone suppressed the growth of human colon fibroblasts (CCD
      18Co) but only when present at three-fold the concentration required to suppress
      the growth of Caco-2 cells. The isoprenoids initiated apoptosis and,
      concomitantly arrested cells in the G1 phase of the cell cycle. Both suppress 3
      hydroxy-3-methylglutaryl CoA reductase activity. beta-Ionone and lovastatin
      interfered with the posttranslational processing of lamin B, an activity
      essential to assembly of daughter nuclei. This interference, we postulate,
      renders neosynthesized DNA available to the endonuclease activities leading to
      apoptotic cell death. Lovastatin-imposed mevalonate starvation suppressed the
      glycosylation and translocation of growth factor receptors to the cell surface.
      As a consequence, cells were arrested in the G1 phase of the cell cycle. This
      rationale may apply to the isoprenoid-mediated G1-phase arrest of tumor cells.
      The additive and potentially synergistic actions of these isoprenoids in the
      suppression of tumor cell proliferation and initiation of apoptosis coupled with
      the mass action of the diverse isoprenoid constituents of plant products may
      explain, in part, the impact of fruit, vegetable and grain consumption on cancer
      risk.

PMID- 10203555
TI  - Decreased plasma membrane thiol concentration is associated with increased
      osmotic fragility of erythrocytes in zinc-deficient rats.
AB  - Zinc deficiency leads to pathological signs that are related to impaired function
      of plasma membrane proteins. The purpose of this study was to assess the effect
      of dietary zinc status on the sulfhydryl (SH) content of erythrocyte plasma
      membranes and erythrocyte function. Three experiments were performed. In the
      first, immature male rats were fed for 21 d either a low-zinc (<1.0 mg/kg) diet
      free choice (-ZnAL), an adequate-zinc (100 mg/kg) diet free choice (+ZnAL), or
      the adequate-zinc diet limited to the intake of -ZnAL pair-mates (+ZnPF). Tail
      blood was sampled to measure osmotic fragility and SH concentration of
      erythrocyte membrane proteins. The zinc-deficient rats were then repleted for 2 d
      and erythrocytes assayed for fragility and SH content. In the second experiment
      blood was sampled at 3-d intervals to determine the time course of change in
      fragility and SH concentration. In the third experiment the SH concentration of
      erythrocyte band 3 protein and the binding of zinc to isolated plasma membranes
      were measured. SH concentration decreased from approximately 75 nmol/mg protein
      to 68 nmol/mg protein during 21 d of depletion and returned to control level
      within 2 d of repletion. There was an inverse relationship between osmotic
      fragility and SH concentration of erythrocyte membrane proteins. Maximal decrease
      in SH occurred within 6 d of consuming the low-zinc diet. The SH content of band
      3 protein isolated from deficient rats was also significantly lower than that of
      pair-fed controls (45 vs. 51 nmol/mg protein). The zinc-binding affinity of
      plasma membrane proteins tended to be decreased by zinc deficiency. In summary,
      low-zinc status lowers the plasma membrane SH concentration, and the decreased
      reducing potential is inversely related to osmotic fragility, and presumably,
      with impaired volume recovery of erythrocytes.

PMID- 10203556
TI  - Postnatal profiles of glycogenolysis and gluconeogenesis are modified in rat pups
      by maternal dietary glucose restriction.
AB  - Because glucose is an important metabolic fuel during perinatal development, the
      effect of restriction of maternal dietary glucose on the developmental profile of
      neonatal glucoregulatory pathways was investigated. Pregnant rats were fed
      isoenergetic diets (0, 12, 24 or 60% glucose) and offspring were killed at seven
      postpartum time periods: 0-2, 4-6, 12-16 and 24 h, and 3, 6 and 15 d. Failure of
      the most restricted pups (0%) to survive 24 h was explained by persistent
      hypoglycemia resulting from the following: 1) insufficient tissue glycogen
      reserves at birth; 2) lower liver glycogen mobilization; 3) delayed phosphorylase
      a induction; and 4) low phosphoenolpyruvate carboxykinase (PEPCK) gene
      expression, all of which occurred despite the lower insulin:glucagon ratio.
      Differences in liver glycogen stores, which had been exhausted in all dietary
      groups by 16 h, could not account for the high d 1 pup mortality in the
      moderately restricted (12 and 24% glucose) groups. However, a certain metabolic
      distress was suggested because these moderately restricted neonates had
      significantly higher liver PEPCK gene expression at 12-16 h but significantly
      lower plasma glucose at 24 h. The high d 3 mortality, confirmed by analysis of
      deviance, was not supported by significant differences in any of the measured
      glucoregulatory indices. We conclude that dietary glucose during pregnancy is
      required for neonatal survival; its restriction not only lowers tissue glycogen
      reserves, but can disrupt the normal gene expression of liver PEPCK and the
      neonatal profile of phosphorylase a activity. Importantly, these observations
      show that the development of neonatal glucoregulatory mechanisms is modified by
      the availability of maternal dietary glucose.

PMID- 10203557
TI  - Growth hormone promotes somatic and skeletal muscle growth recovery in rats
      following chronic protein-energy malnutrition.
AB  - The efficacy of recombinant human growth hormone (GH) and/or a diet enriched in
      protein and energy to improve growth recovery following prolonged malnutrition
      was examined in male rats food-restricted from birth until 120 d of age. At d
      121, restricted rats were randomly assigned to recovery groups receiving either a
      control or enriched diet with or without daily subcutaneous injections of GH.
      Rats were killed after 16 or 47 d of recovery. At d 16, GH treatment stimulated
      liver, heart, plantaris, soleus, carcass and body weight gain and inhibited fat
      gain when compared to recovery controls. Rats receiving GH also exhibited the
      highest serum insulin-like growth factor-I (IGF-I) concentrations and total
      muscle protein. At d 47, GH effects on body and muscle recovery were minimal, and
      differences among recovery groups in serum IGF-I concentration and total muscle
      protein were no longer present. Consumption of an enriched diet increased fat pad
      and liver mass, but did not promote muscle recovery. There were no differences
      among treatment groups in skeletal muscle IGF-I mRNA levels at d 16 or 47. In
      summary, GH had positive effects on somatic and skeletal muscle growth early in
      the recovery process, possibly via endocrine IGF-I-stimulated protein accretion.
      In contrast, the enriched diet promoted fat deposition with no impact on skeletal
      muscle growth recovery.

PMID- 10203559
TI  - Energy and substrate metabolism in patients with active Crohn's disease.
AB  - The aim of the study was to evaluate the possible contribution of changes in
      energy metabolism and substrate oxidation rates to malnutrition in Crohn's
      disease and to assess the effect of enteral nutrition on these parameters. Energy
      metabolism was evaluated by indirect calorimetry in 32 patients with active
      Crohn's disease and 19 age- and sex-matched healthy individuals. Measurements
      were done in the postabsorptive state. Seven out of 32 patients received enteral
      nutrition via a nasogastric tube. In these patients, resting energy metabolism
      was determined at d 0 (postabsorptive), 7, 14 (during full enteral nutrition) and
      15 (postabsorptive). Resting energy expenditure was not significantly different
      between patients and controls, whereas the respiratory quotient (RQ) was lower in
      patients (0.78 +/- 0.05 vs. 0.86 +/- 0.05; P < 0.05). During enteral nutrition in
      7 patients with Crohn's disease, the RQ increased on d 7 compared with d 0 and
      remained high even after cessation of enteral nutrition (d 0, 0.78 +/- 0.03; d 7,
      0.91 +/- 0.04; d 15, 0. 84 +/- 0.05; P < 0.05; d 7 and 15 vs. d 0). No effects of
      enteral nutrition on resting energy expenditure were found. Active Crohn's
      disease is associated with changes in substrate metabolism that resemble a
      starvation pattern. These changes appear not to be specific to Crohn's disease
      but to malnutrition and are readily reversed by enteral nutrition. Enteral
      nutrition did not affect resting energy expenditure. Wasting is a consequence of
      malnutrition but not of hypermetabolism in Crohn's disease.

PMID- 10203558
TI  - Malnutrition modifies pig small intestinal inflammatory responses to rotavirus.
AB  - Infectious diarrheal diseases and malnutrition are major causes of child
      morbidity and mortality. In this study, malnutrition was superimposed on
      rotavirus infection in neonatal piglets to simulate the combined intestinal
      stress of viral enteritis in malnourished infants. Two-day-old piglets were
      assigned to three treatment groups as follows: 1) noninfected, fully nourished;
      2) infected, fully nourished; and 3) infected, malnourished. Intestinal indices
      of inflammation were monitored over the subsequent 2-wk period. Intestinal damage
      and diarrhea were observed within 2 d of rotavirus infection and began to subside
      in nourished piglets by d 9 but persisted through d 16 postinfection in
      malnourished piglets. Rotavirus upregulated small intestinal expression of major
      histocompatibility complex (MHC) class I and class II genes; malnutrition
      intensified MHC class I gene expression and suppressed MHC class II expression.
      Jejunal CD4(+) and CD8(+) T-lymphocyte numbers were elevated for infected,
      nourished piglets on d 2, 9 and 16 postinfection. Malnutrition did not
      significantly affect the local expansion of T cell subsets in response to
      rotavirus. Intestinal prostaglandin E2 (PGE2) concentrations were elevated early
      after rotavirus infection independent of nutritional state. By d 9, PGE2
      concentrations returned to baseline in infected, nourished piglets but remained
      elevated in malnourished piglets, corresponding to diarrhea observations.
      Together, the results identify intestinal indices of inflammation that are
      modulated by malnutrition and prompt reconsideration of current models of
      rotavirus pathophysiology.

PMID- 10203560
TI  - Plasma lycopene concentrations in humans are determined by lycopene intake,
      plasma cholesterol concentrations and selected demographic factors.
AB  - Higher plasma lycopene concentrations have been associated with a reduced risk of
      several chronic diseases. Determinants of lycopene concentrations in humans have
      received limited attention. We had blood lycopene concentrations and lycopene
      consumption data available from 111 participants in a two-center cancer
      prevention trial involving beta-carotene and examined determinants of plasma
      lycopene levels cross-sectionally. The median plasma lycopene level was 0.59
      micromol/L (range 0.07-1.79). Low plasma concentrations of lycopene were
      associated with the following variables in univariate analyses: study site
      (Florida lower than Connecticut, P = 0.001), being nonmarried (P = 0.02), having
      lower income (P = 0.003), being nonwhite race/ethnicity (P = 0.03), having lower
      dietary lycopene intake (r = 0.29, P = 0.002), having lower plasma cholesterol (r
      = 0. 43, P = 0.0001) and triglyceride levels (r = 0.26, P = 0.005), and consuming
      less vitamin C (r = 0.20, P = 0.03). Women had slightly higher plasma lycopene
      levels than men (0.65 vs. 0.58 micromol/L; P = 0.31), despite lower dietary
      intake of lycopene (1,040 vs. 1,320 microg/d; P = 0.50). Plasma lycopene levels
      did not differ in smokers and nonsmokers. In stepwise regression analyses, the
      determinants of plasma lycopene were plasma cholesterol, dietary lycopene, and
      marital status; these three variables explained 26% of the variance in plasma
      lycopene. Relatively few lifestyle and demographic factors were important
      determinants of plasma lycopene levels, with plasma cholesterol, marital status,
      and lycopene intake being of greatest importance.

PMID- 10203561
TI  - Demographic, dietary and lifestyle factors differentially explain variability in
      serum carotenoids and fat-soluble vitamins: baseline results from the sentinel
      site of the Olestra Post-Marketing Surveillance Study.
AB  - Biochemical measures of nutrients or other dietary constituents can be an
      important component of nutritional assessment and monitoring. However, accurate
      interpretation of the nutrient concentration is dependent on knowledge of the
      determinants of the body pool measured. The purpose of this study was to identify
      the determinants of serum carotenoid and fat-soluble vitamin concentrations in a
      large, community-based sample (n = 1042). Multiple linear regression analysis was
      used to examine effects of demographic characteristics (age, sex, race/ethnicity,
      education), health-related behavior (exercise, sun exposure, smoking, alcohol
      consumption), and intake (diet, supplements) on serum retinol, 25-hydroxyvitamin
      D, alpha-tocopherol, phylloquinone, and carotenoid concentrations. Age, sex,
      race/ethnicity, vitamin A intake, and alcohol consumption were found to be
      determinants of serum retinol concentration. Race/ethnicity, vitamin D intake,
      body mass index, smoking status, and sun exposure were determinants of serum 25
      hydroxyvitamin D concentration. Determinants of serum alpha-tocopherol were age,
      sex, race/ethnicity, alpha-tocopherol intake, serum cholesterol, percentage of
      energy from fat (inversely related), supplement use, and body mass index. Age,
      sex, phylloquinone intake, serum triglycerides, and supplement use were
      determinants of serum phylloquinone concentration. Primary determinants of serum
      carotenoids were age, sex, race/ethnicity, carotenoid intake, serum cholesterol,
      alcohol consumption, body mass index, and smoking status. Overall, the
      demographic, dietary, and other lifestyle factors explained little of the
      variability in serum concentrations of retinol (R2 = 0.20), 25-hydroxyvitamin D
      (R2 = 0.24), and the carotenoids (R2 = 0.15-0.26); only modest amounts of the
      variability in serum phylloquinone concentration (R2 = 0.40); and more
      substantial amounts of the variability in serum alpha-tocopherol concentration
      (R2 = 0.62).

PMID- 10203562
TI  - The retention and distribution by healthy young men of stable isotopes of
      selenium consumed as selenite, selenate or hydroponically-grown broccoli are
      dependent on the isotopic form.
AB  - Twenty-seven healthy young men were randomly assigned to diets that supplied low
      (32.6 microg/d) or high (226.5 microg/d) levels of selenium for a 105-d study.
      After consuming the diets for 85 d, subjects were fed a test meal that contained
      74Se in the form of selenite or selenate and 82Se incorporated into
      hydroponically-raised broccoli. Urine, fecal and blood samples were collected
      daily. Isotope absorption was not different (P > 0.05) for selenate and Se in
      broccoli; Se absorption from selenite was highly variable and was not included in
      statistical analyses. Significantly more isotope was absorbed by subjects fed the
      high Se diet (P = 0. 015). Urinary isotope excretion was greater when selenate
      was fed than when broccoli was fed (P = 0.0001), and consequently more Se from
      broccoli (as compared to selenate) was retained (59.2 +/- 2.4 and 36.4 +/- 4.6%
      for Se in broccoli and selenate, respectively; P = 0.0001). Despite the higher
      retention, less isotope from broccoli than from selenate was present in the
      plasma. Plasma proteins separated by gel permeation chromatography showed that
      most of the isotopes were distributed between two medium molecular weight peaks.
      Less isotope was found in plasma proteins of subjects fed the high Se diet, but
      the form of Se had no effect on isotope distribution. These results show that
      dietary Se intake alters the retention of stable isotopes of Se and that humans
      retain and distribute Se from broccoli in a different manner than Se from
      inorganic salts.

PMID- 10203563
TI  - Giardia intestinalis is unlikely to be a major cause of the poor growth of rural
      Gambian infants.
AB  - Parasite-specific plasma immunoglobulins have been used to indicate the presence
      of Giardia intestinalis infection in 60 infants living in a rural area of The
      Gambia. Infants were studied longitudinally between 2 and 8 mo of age. The median
      age for first exposure to G. intestinalis was between 3 and 4 mo, and by 8 mo all
      but 3 infants (95%) showed a positive titer on at least one occasion. Raised
      Giardia-specific IgM titers were associated with reduced weight gain in the 2 wk
      preceding a positive titer, but catch-up growth occurred in the following 2 wk.
      IgM antibody titers were also positively associated with intestinal permeability
      (lactulose/mannitol ratio), urinary lactose excretion, plasma concentrations of
      alpha1-antichymotrypsin and total IgM, IgA and IgG immunoglobulins. However,
      infant growth over the whole 6-mo period (i.e., between 2 and 8 mo of age) was
      not related to mean Giardia-specific antibody titers, nor the time of first
      exposure to the parasite. The data suggest that giardiasis in these very young
      breast-fed children occurs as a mild, acute disease, and its presence could not
      explain the marked, long-term growth faltering observed in many of the subjects.

PMID- 10203564
TI  - Underreporting of habitual food intake is explained by undereating in highly
      motivated lean women.
AB  - Underreporting of habitual food intake can be explained by underrecording and/or
      undereating. This study was designed to discriminate between the two errors
      mentioned, by measuring energy and water balance. Twenty-four lean female
      dieticians were recruited as subjects. Energy intake and water intake were
      measured for 1 wk with a weighed dietary record. Energy expenditure was estimated
      from measurements of resting metabolic rate, and measured physical activity with
      a triaxial accelerometer for movement registration. Water loss was estimated with
      deuterium-labeled water. Energy balance was determined by measuring the change in
      body mass over a nonrecording week (preceding the recording week) and over the
      recording week. Mean energy and water intake were 8.5 +/- 1.0 MJ/d and 2.3 +/-
      0.5 L/d. The change in body mass in the nonrecording week was 0.1 +/- 0.6 kg and
      in the recording week -0.6 +/- 0.8 kg (paired t test; P = 0.02), indicating 16%
      undereating. Recorded water intake plus calculated metabolic water closely
      matched measured water loss (r = 0.93; P = 0.0001), which indicated a high
      recording precision. In conclusion, in the studied group of highly motivated lean
      women, there was 16% underreporting of habitual food intake, which could be
      explained by undereating.

PMID- 10203565
TI  - Nutrient intake of food bank users is related to frequency of food bank use,
      household size, smoking, education and country of birth.
AB  - The number of individuals and families accessing food assistance programs has
      continued to grow throughout the 1990s. Despite the increased health risk among
      low-income people, few studies have addressed nutrient intake throughout the
      month or at the end of the month when food and financial resources are thought to
      be compromised, and no study has described dietary status of a random sample of
      food bank users. Nutrient intakes of adult female and male food bank users in
      metropolitan Montreal, Quebec, Canada, were monitored week-by-week over a month
      by dietitian-administered 24-h recall interviews. A total of 428 participants
      from a stratified random sample of 57 urban area food banks completed all four
      interviews. Mean energy intake, as an indicator of diet quantity, was similar to
      other adult populations (10.2 +/- 4.8 and 7.9 +/- 3.6 MJ for men and women,
      respectively, age 18-49 y) and not related to sociodemographic variables except
      the expected biological variation of age and sex. Macronutrient intake was stable
      throughout the month. Overall median intakes of calcium, vitamin A, and zinc were
      below recommended levels for all age and sex groups. Intakes of several
      micronutrients were related to frequency of food bank use, household size,
      smoking, education, and country of birth. High nutrient intake variability
      characterized these adult food bank users.

PMID- 10203566
TI  - Net postprandial utilization of [15N]-labeled milk protein nitrogen is influenced
      by diet composition in humans.
AB  - The aim of this study was to follow the fate of dietary nitrogen to assess the
      postprandial utilization of purified milk protein and to determine the acute
      influence of energy nutrients. For this purpose, a [15N]-labeling dietary protein
      approach was used. Twenty-five subjects swallowed an ileal tube and ingested [15
      N]-milk protein alone or supplemented with either milk fat or sucrose. The
      absorption and postprandial deamination of dietary protein was monitored for 8 h.
      Sucrose delayed the absorption of protein longer than fat, but the ileal
      digestibility did not differ among groups (94.5-94.8%). Sucrose, but not fat,
      significantly reduced the postprandial transfer of [15N]-milk nitrogen to urea.
      Consequently, the net postprandial protein utilization (NPPU) of milk protein
      calculated 8 h after meal ingestion was 80% when ingested either alone or
      supplemented with fat and was significantly greater with sucrose (NPPU = 85%).
      This study shows that energy nutrients do not affect the nitrogen absorption but
      modify the metabolic utilization of dietary protein in the phase of nitrogen
      gain. Our method provides information concerning the deamination kinetics of
      dietary amino acids and further allows the detection of differences of dietary
      protein utilization in acute conditions. The diet composition should be carefully
      considered, and protein quality must be determined under optimal conditions of
      utilization.

PMID- 10203567
TI  - Increased fecal bile acid excretion and changes in the circulating bile acid pool
      are involved in the hypocholesterolemic and gallstone-preventive actions of
      psyllium in hamsters.
AB  - The lipid-lowering effect of psyllium (PSY) is well established. Enhanced fecal
      bile acid excretion and a stimulation of hepatic bile acid synthesis are
      discussed as primary mechanisms of this action. To further examine the effect of
      bile acid excretion and specifically of compositional alterations in the bile
      acid pool on the cholesterol-lowering and gallstone-preventing action of PSY,
      male golden Syrian hamsters were fed lithogenic diets containing 5 g/100 g fat,
      0.4 g/100 g cholesterol and 0 (control), 4 or 6% PSY or 1% cholestyramine (CHY).
      PSY significantly lowered plasma total cholesterol and triacylglycerol at a
      magnitude comparable to that induced by CHY. Although hepatic cholesteryl ester
      accumulation was completely inhibited by CHY, PSY did not prevent the hepatic
      storage of esterified cholesterol. PSY and CHY caused distinct alterations in the
      bile acid profile. PSY caused a selective reduction of taurine-conjugated bile
      acids, especially of taurochenodeoxycholate. As a result, the glycine:taurine
      conjugation and the cholate:chenodeoxycholate ratios were significantly higher in
      PSY-fed hamsters. PSY and CHY normalized the lithogenic index and prevented
      cholesterol gallstone formation compared with controls. Daily fecal bile acid
      excretion was approximately 400% greater in hamsters fed 6% PSY, whereas CHY
      caused an 11-fold increase. Daily neutral sterol excretion did not differ in PSY
      fed hamsters but was >100% greater in those fed CHY than in controls. These data
      emphasize the potent lipid-lowering effect of PSY. Increased fecal bile acid
      excretion and alterations of the circulating bile acid pool by removal of
      dihydroxy bile acids (e.g., taurochenodeoxycholate) appear to be main modulators
      of the hypocholesterolemic action of PSY by leading to an up-regulation of
      hepatic bile acid synthesis.

PMID- 10203568
TI  - Ineffective vitamin D synthesis in cats is reversed by an inhibitor of 7
      dehydrocholestrol-delta7-reductase.
AB  - Changes in plasma 25-hydroxyvitamin D (25-OHD) were used as an index of vitamin D
      status of cats. Plasma 25-OHD concentration of kittens given a purified vitamin D
      free diet and exposed to direct summer sun for 15 h/wk declined at a similar rate
      as kittens given the same diet kept indoors. Similarly, plasma 25-OHD of kittens
      exposed to ultraviolet (UV) lamps declined at a similar rate as kittens not
      exposed, and these kittens developed clinical signs of vitamin D deficiency.
      Eight weaned kittens were given the vitamin D-free purified diet until their
      plasma concentrations of 25-OHD were < 5 nmol/L. They then had the hair on their
      backs clipped at weekly intervals and were paired on the basis of skin color and
      exposed to UV light for 2 h/d. One member of each pair was given an inhibitor of
      7-dehydrocholesterol (5, 7-cholestradien-3beta-ol)-delta7-reductase (EC 1.3.1.21)
      in the diet. Cats receiving the inhibitor had a progressive increase in 25-OHD
      concentration of plasma with time to 91 +/- 22 nmol/L (mean +/- SEM), whereas
      cats not receiving the inhibitor had plasma 25-OHD concentrations that were not
      detectable (P < 0.001). Biopsy samples of skin from cats receiving the inhibitor
      had more than five times the concentration of 7-dehydrocholesterol (P < 0.001)
      than the skin of control cats. Low concentration of 7-dehydrocholesterol
      (presumably due to high activity of the reductase) in the skin of cats is the
      major impediment to effective vitamin D synthesis. Analysis of wild caught
      potential prey of cats indicated that these animals could supply adequate vitamin
      D to meet the requirement of growing kittens.

PMID- 10203569
TI  - Plasma 25-hydroxyvitamin D in growing kittens is related to dietary intake of
      cholecalciferol.
AB  - Vitamin D synthesis by growing kittens exposed to ultraviolet light is
      ineffective. Concentration of 25-hydroxyvitamin D (25-OHD) in plasma (the most
      useful index of vitamin D status) was measured in six groups each of seven
      kittens given a purified diet (12 g calcium and 8 g phosphorus/kg, calculated
      metabolizable energy = 20 kJ/g) that contained either 0.0, 3.125, 6.25, 12.5,
      18.75 or 25 microg of cholecalciferol/kg diet. All kittens received these diets
      from 9 to 22 wk of age, and the two groups given the 0.0 and 3.125 microg
      cholecalciferol/kg treatments continued to receive the diets until they were 34
      wk old. Total and ionizable calcium and phosphorus in plasma were not affected by
      treatments. No adverse clinical changes were observed or found on radiographic
      examination of the kittens at 22 or 34 wk of age. Plasma concentration of 25-OHD
      was linearly related (r2 = 0.99, P < 0.001) to dietary intake of cholecalciferol.
      Plasma concentration of 25-OHD in kittens given the diet without added vitamin D
      was significantly less at 22 wk than at 9 wk, whereas kittens receiving the diet
      containing 3.125 microg cholecalciferol/kg had significantly higher 25-OHD
      concentrations at 22 and 34 wk than at 9 wk of age. Kittens given the 6.25 microg
      cholecalciferol/kg diet had plasma 25-OHD concentrations at 22 wk > 50 nmol/L
      which is considered replete for humans. An allowance of 6. 25 microg (250 IU) of
      cholecalciferol/kg diet is suggested to provide a margin of safety.

PMID- 10203570
TI  - Availability of food folate in humans.
AB  - The aim of our study was to determine whether the area-under-the-plasma-response
      curve method with the positive area (AUC+) as primary analysis variable is
      suitable to evaluate the availability of food folate in humans. Healthy
      volunteers (n = 20) received four test meals in a randomized, four-period cross
      over design as follows: meal A, 600 g spinach; meal B, 300 g spinach; meal C, 0.4
      mg folic acid in water; meal D, folate-free control meal. Blood samples were
      drawn before administration of the test meals and up to 10 h postprandially.
      Plasma folate was significantly increased for up to 6 h after uptake of spinach
      and folic acid (P < 0.007), whereas the response curve after the control meal
      decreased slightly but significantly (P < 0.007). To calculate the net increase
      of plasma folate, the values were corrected by the individual predose
      concentrations. The AUC+ was calculated with these corrected values. The mean
      AUC+ was highest after consumption of meal A (71.2 +/- 24.0 h x nmol/L) followed
      by meal C (61.8 +/- 23. 8 h x nmol/L) and meal B (41.4 +/- 19.4 h x nmol/L). The
      AUC+ after meal B was significantly lower than after the other two meals (P < 0.
      05). The results suggest that the AUC method with multiple blood sampling is
      useful for assessing the availability of food folate in humans.

PMID- 10203571
TI  - The Department of Molecular Medicine at the University of Istanbul, Institute of
      Experimental Medical Research.

PMID- 10203574
TI  - Chemotherapy cytotoxicity of human MCF-7 and MDA-MB 231 breast cancer cells is
      altered by osteoblast-derived growth factors.
AB  - One-third of women with breast cancer will develop bone metastases and eventually
      die from disease progression at these sites. Therefore, we analyzed the ability
      of human MG-63 osteoblast-like cells (MG-63 cells), MG-63 conditioned media (MG
      63 CM), insulin-like growth factor I (IGF-I), and transforming growth factor beta
      1 (TGF-beta1) to alter the effects of adriamycin on cell cycle and apoptosis of
      estrogen receptor negative (ER-) MDA-MB-231 and positive (ER+) MCF-7 breast
      cancer cells, using cell count, trypan blue exclusion, flow cytometry, detection
      of DNA fragmentation by simple agarose gel, and the terminal deoxynucleotidyl
      transferase (TdT)-mediated nick end-labeling method for apoptosis (TUNEL assay).
      Adriamycin arrested MCF-7 and MDA-MB-231 cells at G2/M phase in the cell cycle
      and inhibited cell growth. In addition, adriamycin arrested the MCF-7 cells at
      G1/G0 phase and induced apoptosis of MDA-MB-231 cells. Exogenous IGF-I partially
      neutralized the adriamycin cytotoxicity/cytostasis of cancer cells. MG-63 CM and
      TGF-beta1 partially neutralized the adriamycin cytotoxicity of MDA-MB-231 cells
      but enhanced adriamycin blockade of MCF-7 cells at G1/G0 phase. MG-63 osteoblast
      like cells inhibited growth of MCF-7 cells while promoting growth and rescued MDA
      MB-231 cells from adriamycin apoptosis in a collagen co-culture system. These
      data suggest that osteoblast-derived growth factors can alter the chemotherapy
      response of breast cancer cells. Conceivably, host tissue (bone)-tumor cell
      interactions can modify the clinical response to chemotherapy in patients with
      advanced breast cancer.

PMID- 10203572
TI  - Mdm2: the ups and downs.

PMID- 10203575
TI  - Rate and severity of HIV-associated dementia (HAD): correlations with Gp41 and
      iNOS.
AB  - BACKGROUND: Fifteen to thirty percent of AIDS patients develop some type of
      neurologic disorder during the course of their illness and the vast majority of
      these neurologic disorders will be HIV-associated dementia (HAD). These patients
      can exhibit varying degrees of severity and rates of progression of HAD.
      Neuropathologic variables that are associated with the rate of progression of HAD
      are not known. MATERIALS AND METHODS: Tissue was collected at autopsy from the
      Johns Hopkins University HIV Neurology Program. Seventy-one AIDS patients of this
      prospectively characterized population were followed until death to obtain
      information on dementia severity and the rate of neurological progression.
      Immunoblot analysis of immunological nitric oxide synthase (iNOS), HAM56, gp41,
      p24, gp120, and beta-tubulin was performed and the levels of iNOS, HAM56, gp41,
      and p24 were normalized to beta-tubulin and analyzed for significance by means of
      the Kruskal-Wallis test for multiple groups. RESULTS: We have identified unique
      groups within this spectrum and designated them slow, moderate, and rapid
      progressors. Slow and moderate progressors' neurological progression occurs over
      a course of months to years, whereas the rapid progressors' disease shows rapid
      increases in severity over weeks to months. In the present study we demonstrate
      that the severity and rate of progression of HAD correlates significantly with
      levels of the HIV-1 coat protein, gp41, iNOS, and HAM56, a marker of
      microglial/macrophage activation. CONCLUSION: The severity and rate of
      progression of HAD correlates with indices of immune activation as well as levels
      of iNOS and gp41. There appears to be a threshold effect in which high levels of
      gp41, iNOS, and immune activation are particularly associated with severe
      (Memorial Sloan-Kettering score 3 to 4) and rapidly progressive HAD.

PMID- 10203576
TI  - The myocardial profile of the cytosolic isozymes of creatine kinase is apparently
      not related to cyanosis in congenital heart disease.
AB  - BACKGROUND: CKMB, the cardiac-specific heterodimer of cytosolic creatine-kinase
      (CK), is developmentally and physiologically regulated, tissue hypoxia being a
      proposed regulator. In patients with cyanotic heart disease the myocardium is
      perfused with partially saturated blood. We questioned whether the myocardium of
      cyanotic subjects contains higher proportions of CKMB. MATERIALS AND METHODS: CK
      activity, the distribution of cytosolic CK isozymes, activity of lactic
      dehydrogenase (LDH), and tissue protein content were determined in obstructive
      tissues removed at corrective surgery of patients with congenital heart defects.
      Cyanotic (n = 13) and acyanotic (n = 12) subjects were compared. RESULTS: In
      cyanotic and acyanotic patients, CK activity was 8.4 +/- 0.6 and 7.6 +/- 0.6
      IU/mg protein and the proportion of CKMB was 21 +/- 1.4 and 22 +/- 2. 0% (mean +/
      S.E.M), respectively. In the two groups of patients, the activity related to the
      B subunit corresponded to the steady-state level of the CKBmRNA. The tissue
      content of protein and the activities of CK and LDH were similar in cyanotic and
      acyanotic subjects and increased with the age. CONCLUSIONS: The lack of
      difference in CKMB distribution between the cyanotic and acyanotic patients may
      either indicate that hypooxygenation is not a regulator of CK isozyme expression,
      or may be attributed to the already high proportion of this isozyme in
      hypertrophied, obstructive tissues. Recruitment of additional CKMB, in the
      cyanotic hearts, may thus not be required.

PMID- 10203579
TI  - Bcl-2 protects against beta-lapachone-mediated caspase 3 activation and apoptosis
      in human myeloid leukemia (HL-60) cells.
AB  - We previously demonstrated that beta-lapachone (beta-lap) killed cancer cells
      solely by apoptosis. Beta-Lap induced apoptosis in HL-60 cells in a dose
      dependent manner as measured by flow cytometry and DNA ladder formation. Cell
      cycle changes, such as accumulations in S and G2-phases, were not observed.
      Apoptosis was accompanied by activation of caspase 3 and concomitant cleavage of
      poly(ADP-ribose) polymerase (PARP) to an 89 kDa polypeptide. PARP cleavage was
      blocked by zDEVD-fmk or zVAD-fmk, caspase-specific cleavage site inhibitors.
      Retrovirally introduced bcl-2 prevented beta-lap-mediated caspase 3 activation
      and PARP cleavage and increased the viability of Bcl-2-expressing HL-60 cells
      compared to cells with vector alone. Various beta-lap-related analogs (e.g.,
      dunnione and naphthoquinone derivatives) induced equivalent apoptosis in HL-60
      cells, but no compound was more effective than beta-lap. These data provide
      further evidence that the primary mode of cell killing by beta-lap is by the
      initiation and execution of apoptosis in human cancer cells.

PMID- 10203577
TI  - Suppressive effects of anti-inflammatory agents on human endothelial cell
      activation and induction of heat shock proteins.
AB  - BACKGROUND: Studies from our laboratory have shown that the earliest stages of
      atherosclerosis may be mediated by an autoimmune reaction against heat shock
      protein 60 (Hsp60). The interactions of Hsp60-specific T cells with arterial
      endothelial cells (EC) require expression of both Hsp60 and certain adhesion
      molecules shown to be induced simultaneously in EC by mechanical and other types
      of stress. Recently, it was shown that suppression of T cell-mediated immune
      responses by cyclosporin A (CyA) enhanced atherosclerotic lesion formation in
      mice. In contrast, aspirin was found to lower the risk of myocardial infarction
      in men. These conflicting observations may be due to different effects of anti
      inflammatory agents on adhesion molecule and Hsp expression in EC, respectively.
      MATERIAL AND METHODS: In the present study, we analyzed the effects of CyA,
      aspirin, and indomethacin on T cell proliferation using a proliferation assay. To
      explore the expression of adhesion molecules, monocyte chemoattractant protein-1
      (MCP-1), and Hsp60 in human umbilical vein endothelial cells (HUVECs), Northern
      blot analyses were used. To examine the activation status of the transcription
      factors nuclear factor kappaB (NF-kappaB) and heat shock factor-1 (HSF-1),
      electrophoretic mobility shift assays were performed. RESULTS: With the exception
      of indomethacin, the used immunosuppressive and anti-inflammatory agents
      significantly inhibited T cell proliferation in response to influenza virus
      antigen in a dose-dependent manner. Interestingly, CyA and indomethacin did not
      suppress tumor necrosis factor-alpha (TNF-alpha)-induced adhesion molecule
      expression on HUVECs, whereas aspirin had an inhibitory effect. These
      observations correlated with the modulation of NF-kappaB activity in EC. All
      agents tested induced expression of Hsp60 6 hr after application. In addition,
      aspirin and indomethacin, but not CyA, induced Hsp70 expression in HUVECs that
      correlated with induction of HSF-1 activity. CONCLUSION: Our results show that
      the tested agents (except indomethacin) are inhibitors of the T cell-mediated
      immune response, as expected, that aspirin is an effective suppressor of adhesion
      molecule expression, and that all three agents can induce Hsp60 in HUVECs. These
      data provide the molecular basis for the notion that (1) part of the anti
      atherogenic effect of aspirin may be due to the prevention of the adhesion of
      sensitized T cells to stressed EC; (2) that part of the atherosclerosis-promoting
      effect of CyA may be due to its potential as an inducer of Hsp60 expression and
      its inability to down-regulate adhesion molecule expression on EC; and (3) that
      down-regulation of MCP-1 expression by aspirin may result in decreased
      recruitment of monocytes into the arterial intima beneath stressed EC.

PMID- 10203578
TI  - Expression of green fluorescent protein in oligodendrocytes in a time- and level
      controllable fashion with a tetracycline-regulated system.
AB  - Developments in transgenic technology have greatly enhanced our ability to
      understand the functions of various genes in animal models and relevant human
      diseases. The tetracycline (tet)-regulated transactivation system for inducing
      gene expression allowed us to control the expression of exogenous genes in a
      temporal and quantitative way. The ability to manipulate a cell-specific promoter
      enabled us to express one particular protein in a single type of cell. The
      combination of a tetracycline system and a tissue-specific promoter has led us to
      the development of an innovative gene expression system, which is able to express
      genes in a cell type-specific and time- and level-controllable fashion. An
      oligodendrocyte-specific myelin basic protein (MBP) gene promoter controls the
      reversed tet-inducible transactivator. The green fluorescent protein (GFP) gene
      was placed under the control of the human cytomegalovirus (CMV) basic promoter in
      tandem with seven tet-responsive elements (TRE), binding sites for the activated
      transactivator. Upon the addition of doxycycline (DOX, a tetracycline
      derivative), tet transactivators became activated and bound to one or more TRE,
      leading to the activation of the CMV promoter and the expression of GFP in
      oligodendrocytes. We have successfully expressed GFP and luciferase at high
      levels in oligodendrocytes in a time- and dose-dependent fashion. In the absence
      of DOX, there was almost no GFP expression in oligodendroglial cultures. Graded
      levels of GFP expression were observed after induction with DOX (0.5 to 12.5
      microg/ml). Our data indicate that this inducible gene expression system is
      useful for the study of gene function in vivo and for the development of
      transgenic animal models relevant to human diseases such as multiple sclerosis.

PMID- 10203580
TI  - Is digitalis a therapy for breast carcinoma?
AB  - We have previously reported effects on breast carcinoma by digitalis on patients
      in vivo with significant effects on cytometric features and recurrence rate.
      Increased attention is now paid to the anti-proliferative and apoptosis inducing
      effect on cancer cells in vitro by glycosides from foxglove as well as by some
      other glycosides. The present study is a long-term follow-up (22.3 years) of 175
      patients with breast carcinoma, of which 32 were on digitalis treatment, when
      they acquired their breast carcinoma. There was a lower death rate (6%) from
      breast carcinoma among the patients on digitalis, when compared with patients not
      on digitalis (34%). Also proliferation/aneuploidy was less pronounced of the
      tumors in patients on digitalis. These observations were statistically
      significant although the statistical analysis was hampered in the life-table
      analysis by the fact that only 2/32 patients on digitalis died from breast
      cancer. Serious consideration should be given to the effects of digitalis
      derivatives on cancer cells in cancer drug design. This field of research is not
      sufficiently explored and holds promise to contain drugs superior to present-day
      adjuvant therapy both with respect to effects and side-effects.

PMID- 10203581
TI  - Loci for efficient detection of microsatellite instability in hereditary non
      polyposis colorectal cancer.
AB  - Most hereditary non-polyposis colorectal cancer (HNPCC) is due to germline
      mutations in DNA mismatch repair genes. Tumors arising as a result of these
      mutations display instability in microsatellites, which are short tandem repeats
      of DNA that are distributed throughout the genome. Although a subset of sporadic
      colorectal carcinomas also have microsatellite instability (MSI), the phenotype
      is a useful screening test in identifying patients with HNPCC caused by mutations
      in mismatch repair (MMR) genes. Studies have shown that some microsatellite
      markers are more efficient than others in identifying tumors with MSI.
      Furthermore, the frequency of instability can be assessed by categorizing
      patients into high (MSI-H, >/= 30-40% positive markers), low (MSI-L), and
      microsatellite stable (MSS) groups. Using a panel of 28 microsatellite markers,
      tumor and normal DNA from 10 HNPCC patients was used to identify the five most
      efficient markers for detecting MSI (BAT26, D2S123, FGA, D18S35, and TP53-DI).
      Each of the five markers detected MSI in 80-100% of the cases examined. We then
      expanded the sample size to 17 tumors from HNPCC patients. Each case had evidence
      for a mutation in either hMSH2 or hMLH1. We compared the efficiency of our panel
      of five best markers with another panel of five markers (BAT25, BAT26, D2S123,
      D17S250, and D5S346) identified as being efficient markers for detection of MSI
      at a recent NCI workshop. Our five selected markers were more efficient (85% vs.
      79%) in detecting MSI. However, using either panel, 100% of the cases fell into
      the MSI-H category and the probability of misclassifying an MSI-H case as MSI-L
      is very low (0.002-0.008). We also examined four cases meeting the Amsterdam
      criteria for HNPCC, but with no evidence for mutation in either the hMSH2 or
      hMLH1 gene. With our panel, three were classified as MSI-H, while only two were
      classified as such with the NCI reference panel. The probability of
      misclassifying an MSI-L case as an MSI-H, using a panel of five markers is high
      (0.263).

PMID- 10203582
TI  - Spontaneous conversion to estrogen receptor expression by the human breast
      epithelial cell line, MCF-10A.
AB  - The human breast epithelial cell line, MCF-10A, derived from tissue from a woman
      undergoing a cutaneous mastectomy for fibrocystic breast disease, is negative for
      estrogen receptor expression, has undergone minimal genetic changes, retains many
      of the characteristics of normal breast epithelium and fails to exhibit growth in
      nude mice. When transfected with a functional copy of the estrogen receptor, both
      ER and MDM2 expression are negatively regulated by the presence of increasing
      concentrations of estradiol, as previously reported. We obtained the MCF-10A cell
      line from the American Type Culture Collection and confirmed that it was negative
      for ER expression. After approximately 20 passages under differing growth
      conditions, one subline was determined to be positive for ER expression. Growth
      of this ER-positive subline in phenol red-free media supplemented with charcoal
      dextran stripped serum in the presence of nanomolar concentrations of estradiol
      failed to modulate ER and MDM2 expression, and induced expression of both pS2 and
      cathepsin D. Simultaneously with these observations, we observed that this
      subline, unlike the parent MCF-10A line, overexpressed P53 protein with a nuclear
      localization. Intermediate levels of the P53-inducible protein p21 WAF1/Cip1 were
      also detected in the ER-positive subline whereas levels of this protein in the
      parent subline were barely detectable, as measured by immunohistochemical
      methods. We conclude from these studies that ER expression and P53 alteration may
      constitute early steps in progression of malignant potential for breast cancer
      development.

PMID- 10203583
TI  - Analysis of radiation pneumonitis and radiation-induced lung fibrosis in breast
      cancer patients after breast conservation treatment.
AB  - We examined radiation pneumonitis in breast cancer patients after breast
      conservation treatment (BCT) and analysed the degree of radiation-induced lung
      fibrosis by computed tomographies of the chest (chest CT). Fifty-two breast
      cancer patients were treated with BCT, including breast irradiation and
      chemotherapy. These patients symptomatic of radiation pneumonitis were examined
      every two to four weeks. Chest X-rays and chest CT were performed about one year
      after irradiation. symptoms due to radiation pneumonitis was registered in 9.6%
      of patients. lungs showed fibrotic changes by chest CT in 90% of the cases.
      Concurrent or alternative chemotherapy increased the incidence of symptomatic
      radiation pneumonitis and, to a certain extent, the degree of fibrotic change in
      the lung after BCT.

PMID- 10203584
TI  - Expression of platelet-derived endothelial cell growth factor in prostatic
      adenocarcinoma.
AB  - Angiogenesis is thought to play critical roles in local tumor growth and eventual
      metastasis. No studies have examined the expression of platelet-derived
      endothelial cell growth factor (PD-ECGF) in prostatic tissues. Prostatic tissues
      were obtained from 36 prostatic adenocarcinoma patients. We assessed the
      expression of PD-ECGF using ELISA and immunohistochemistry. The mean level of PD
      ECGF in prostatic adenocarcinomas was higher than that in neighboring normal
      prostatic tissues in ELISA. Immunohistochemistry showed that the expressions of
      PD-ECGF, which were associated with increase of microvessel count, were found in
      the endothelial cells, macrophages, lymphocytes, or fibroblasts. These results
      suggest that PD-ECGF is involved in the development of prostatic adenocarcinoma.

PMID- 10203585
TI  - Angiostatic activity of synthetic inhibitors of urokinase type plasminogen
      activator.
AB  - We hypothesize that tumor angiogenesis can be limited by the reduction of
      enzymatic activity of the urokinase type plasminogen activator. The proposed
      mechanism is elimination of proteolytic activity by the advancing tip of
      capillaries which utilize proteolysis to produce space needed for vessel
      expansion. To test our hypothesis, we have investigated the angiostatic activity
      of synthetic low molecular weight inhibitors of urokinase: amiloride,
      benzamidine, EGCG, B428, and B623 using the chicken embryo corioallantoic
      membrane (CAM) model. We found that all tested inhibitors of urokinase cause a
      significant reduction of angiogenesis.

PMID- 10203586
TI  - Clinicopathological significance of erbB-2 expression in colorectal carcinoma.
AB  - The level of erbB-2 expression in both the tumour tissue and serum of individuals
      with colorectal carcinoma is unclear. This study aims to clarify expression
      levels and to relate these to a range of clinicopathological parameters.
      Overexpression of erbB-2 was detected in 25% of patient tumour tissue and an
      elevation in serum concentration of the extracellular domain (ECD) of erbB-2 was
      detected in 10% of patients. Surprisingly, an elevated serum ECD concentration
      did not correlate with erbB-2 overexpression within the primary tumour, and
      neither tumour or serum levels of the protein correlated with any
      clinicopathological parameters examined. These results indicate that erbB-2
      overexpression in tissue and serum are not uncommon in colorectal carcinoma, but
      may not be useful as predictors of disease outcome.

PMID- 10203587
TI  - Pleomorphic leiomyosarcoma of the soft parts: a reassessment by histology and
      immunohistochemistry of pleomorphic soft tissue sarcomas.
AB  - Histologically it is often difficult to differentiate malignant fibrous
      histiocytoma (MFH) from leiomyosarcoma. Sixty-three cases formerly diagnosed as
      pleomorphic soft tissue sarcomas were examined by immunohistochemistry. We
      identified three different types according to its positivity for the myogenic
      markers: A) positive cells with a fascicular pattern, 13 cases (26%); B) a small
      number of scattered positive cells, 29 cases (57%); C) negative for markers, 9
      cases (17%). We reassessed 51 MFHs as follows: A type as pleomorphic
      leiomyosarcoma, B+C types as MFH. Pleomorphic leiomyosarcomas were also positive
      for collagen type IV around the compactly arranged individual tumor cells. An
      imunohistochemical analysis and detection of fascicular structures are thus
      considered to be necessary in order to distinguish between leiomyosarcoma and
      MFH.

PMID- 10203588
TI  - Expression of p53 and p21CIP1/WAF1 proteins in oral epithelial dysplasias and
      squamous cell carcinomas.
AB  - The expression of tumor suppressor gene, p53 and cyclin-dependent kinase
      inhibitor, p21 in oral epithelial dysplasia and oral squamous cell carcinoma
      (OSCC) was examined immunohistochemically and its relationship with
      clinicopathological findings was analyzed. Among 24 epithelial dysplasias, 4
      cases (17%) expressed p53 protein and 23 cases (96%) expressed p21 protein. On
      the other hand, expression of p53 was observed in 64% of OSCCs, and expression of
      p21 was observed in 77% of OSCCs. In the analyses of the correlation between the
      expression of p53 and p21 in epithelial dysplasia and OSCC, 79% of epithelial
      dysplasias were p53-negative and p21-positive, compared to 25% of the OSCCs. p21
      expression did not correlate with p53 expression. These results were also
      demonstrated in OSCC cell lines by western blot analysis. Cumulative survival
      rate of the patients p53-negative and p21-positive was higher than those p53
      positive and p21-negative, those p53-negative and p21-negative and those p53
      positive and p21-positive. These findings suggest that p53 expression and p21
      negative expression may involve in neoplastic transformation of oral epithelium.
      In the present study, we did not observe correlation between the expression of
      p53 and p21 proteins in OSCC. p21 expression may be regulated by p53-independent
      pathways as well as p53-dependent ones. However, combination of the p21 and p53
      expression may be useful as a prognostic marker.

PMID- 10203589
TI  - The usefulness of pharmacokinetic modulating chemotherapy (UFT plus 5FU) in the
      treatment of unresectable colorectal carcinomas.
AB  - This study was performed to improve the prognosis of unresectable (primary non
      curative and recurrent) colorectal carcinoma by using pharmacokinetic modulating
      chemotherapy (PMC), a combination of oral UFT and continuous venous 5FU infusion.
      The subjects were 120 patients who were prospectively selected for this study.
      The patients selected PMC or alternative treatment. Fifty-six patients received
      PMC. The PMC group received 200-400 mg/body/ day UFT orally 5-7 days per week and
      600 mg/m2/24 h 5FU infusion once a week. PMC markedly improved the median
      survival period (26.6 months vs. 9.2 months P<0.000001). This significant
      improvement as observed in unresectable primary colorectal carcinoma (P=0.0003),
      recurrent tumors (P<0.00001), local extension (P=0.01), lung metastases (P=0.
      03), liver metastases (P=0.0001), and peritoneal seedings (P=0.02). One of 56
      patients who received PMC developed grade 4 toxicity. PMC significantly improved
      the prognosis of unresectable colorectal carcinoma which has a low survival rate.
      PMC also indicated tolerable compliance and cost effectiveness.

PMID- 10203590
TI  - Inhibition of liver metastasis of colon cancer by in vivo administration of anti
      vascular endothelial growth factor antibody.
AB  - Cancer metastasis via blood vessels is a complicated process involving a number
      of stages. Vascularization in the cancer stroma is essential for the metastatic
      process. Vascular endothelial growth factor (VEGF) is an angiogenic factor, and
      has important roles in tumor progression or metastasis. In this study, we
      developed a polycolonal antibody to VEGF and examined whether the anti-VEGF
      antibody could inhibit the metastasis of human xenografts expressing VEGF in nude
      mice. The xenograft Col-23-JCK expressing VEGF formed metastatic lesions in the
      liver and/or pancreas when inoculated via the portal vein (splenic vein) into
      nude mice. The anti-VEGF polyclonal antibody inhibited metastasis to the liver
      and/or pancreas (4.75+/- 3.62, anti-VEGF-treated vs. 9.73 +/- 8.24, w/o anti-VEGF
      treatment; Student's t-test, p=0.035). Vascularity in the metastatic lesions was
      also decreased by anti-VEGF treatment. These results suggest that anti-VEGF
      antibody administration may be therapeutically useful for prevention of colon
      cancer metastasis.

PMID- 10203591
TI  - Effects of interferon-alpha on cellular proliferation and adhesion of breast
      carcinoma cells.
AB  - We examined the potent inhibitory effects of interferon-alpha (IFN-alpha) on both
      cellular adhesion and cell proliferation of MCF-7 breast carcinoma cells. When
      MCF-7 cells were exposed to IFN-alpha at a concentration of 5x10(3) IU/ml for 5
      days, cell proliferation was markedly inhibited. Cell attachment assay
      demonstrated that incubation with IFN-alpha for up to 48 h reduced alpha2beta1
      integrin-mediated cellular adhesion. However, fluorescence activated cell sorter
      (FACS) analysis revealed that incubation with IFN-alpha for 24 h had no effect
      upon the cell surface expressions of either alpha2 and beta1 integrin on MCF-7
      cells. These antiproliferative and antiadhesive actions of IFN-alpha may be
      applied to treatment for patients with metastatic breast carcinoma.

PMID- 10203592
TI  - Aphidicolin glycinate inhibits human neuroblastoma cell growth in vivo.
AB  - Aphidicolin is a fungal derived tetracyclic diterpene antibiotic. It is
      selectively toxic for neuroblastoma (NB) cells in vitro but has no significant
      effects on the viability of normal human cells and a variety of other tumor
      entities. We evaluated the antitumoral effects of the water soluble ester
      aphidicolin glycinate (AphiG) on established human NB xenografts from UKF-NB-3
      cells in athymic (nude) mice. Furthermore, we explored the efficacy of direct
      intraneoplastic and systemic delivery of AphiG. Systemic administration of AphiG
      (60 mg/kg intraperitoneally, twice per day on 10 consecutive days) significantly
      suppressed tumor growth but was not able to induce any cures. In contrast,
      intratumoral AphiG injections (60 or 40 mg/kg/twice a day for 4 days) induced
      complete tumor regression. Two weeks after the end of treatment no tumor cells
      were microscopically detectable. Animals were free of tumor for more than 90
      days. Histologic examination of inner organs and bone marrow did not reveal any
      apparent toxic effects of AphiG. These data strongly indicate that AphiG deserves
      further evaluation as a specific treatment for neuroblastoma.

PMID- 10203593
TI  - Expression of Mad1 protein inhibits proliferation of cancer cells and inversely
      correlated with Myc protein expression in primary gastric cancer.
AB  - We performed immunohistochemical assay for Mad1 and Myc protein in 76 gastric
      cancer tissues. Cancers with reduced Mad1 expression had high proliferative index
      (S and G2/M-phase) and there was inverse correlation between Mad1 and Myc
      expression in the same cancer cells. There was no significant correlation between
      expression of Mad1 and cell differentiation or extent of the disease. There was a
      trend that reduced expression of Mad1 was associated with poor survival of the
      patients. Mad1 may influence biologic behavior of cancer cell by inhibiting
      transcriptional activity of Myc and reduced levels of Mad1 expression seem to be
      associated with carcinogenesis in human gastric cancer.

PMID- 10203594
TI  - Clinical significance of immunohistochemical Bcl-2 expression in invasive breast
      carcinoma.
AB  - The immunohistochemical expression of bcl-2 protein, and its correlations with
      clinicopathological features and prognosis were studied in patients with invasive
      breast carcinoma. Bcl-2 positive expression significantly correlated with hormone
      receptor positivity and histological tumor differentiation, and inversely
      correlated with p53 overaccumulation. No correlation was observed between bcl-2
      expression and patient age, menopausal status, tumor size, and lymph node
      metastasis. Survivals of stage I to III patients who had not received adjuvant
      hormonal therapy showed no difference between bcl-2-positive and -negative
      tumors, even if patients were divided as with or without adjuvant chemotherapy,
      or with or without nodal involvement. In consequence, immunohistochemical bcl-2
      positivity correlates with positive hormone receptors and well differentiated
      phenotypes in invasive breast carcinoma, however, it might not predict response
      to adjuvant chemotherapy and not be a favorable predictive value in patients
      treated without adjuvant hormonal therapy.

PMID- 10203596
TI  - Hepatic arterial infusion chemotherapy with continuous low dose administration of
      cisplatin and 5-fluorouracil for multiple recurrence of hepatocellular carcinoma
      after surgical treatment.
AB  - To date, conventional treatments for multiple intrahepatic recurrence of
      hepatocellular carcinoma (HCC) after surgery are unsuccessful. The aim of this
      retrospective study was to evaluate the prognostic effectiveness of a new
      infusion chemotherapy of cisplatin (CDDP) and 5-fluorouracil (5-FU) via hepatic
      artery for HCC with multiple intrahepatic recurrence. Fifty-two patients, who had
      postoperative multiple recurrence of HCC (more than 3 tumors), were enrolled in
      this study. Thirty-one patients were treated by hepatic arterial infusion
      chemotherapy via a subcutaneously implanted injection port. A one-week course of
      this treatment consisted of daily administration of cisplatin (10 mg for 1 h on
      days 1-5) and subsequent daily administration of 5-fluorouracil (250 mg for 5 h
      on days 1-5). Three to six sequential one-week courses were performed (the CDDP,5
      FU group). Twenty-one patients underwent conventional interventional therapies
      including transcatheter arterial chemoembolization, lipiodolization (the
      conventional group). The complete response rate and the effective response rate
      in the CDDP,5-FU group were 29.0% and 71.0%, respectively. The 5-year survival
      rate in this group was 45.7%, which was significantly better than that in the
      conventional group. Based on multivariate analysis, CDDP,5-FU hepatic arterial
      infusion chemotherapy was found to be significant in prolonging survival, and
      this treatment achieved favorable therapeutic results for multiple recurrence of
      HCC. As part of a multidisciplinary approach this treatment is expected to
      improve the prognosis of patients with advanced HCC.

PMID- 10203595
TI  - The effects of nicotinamide plus carbogen or pions for microscopic SCCVII tumors.
AB  - We evaluated the sensitizing effect of nicotinamide plus carbogen (N&C) and the
      relative biological effectiveness (RBE) of pions on microscopic tumors where
      necrotic tumor centers have not yet been established. Female C3H/He mice and
      SCCVII tumors were used. The irradiation started two days after tumor
      implantation. In experiment 1, the tumor beds were irradiated at various doses
      with 250 KVp photons in 5 fractions over 5 days. Nicotinamide (500
      mg/kg/mouse/day in 0.2 ml) was injected intraperitoneally (i.p.) 60 min before
      irradiation, and carbogen (95% O2 + 5% CO2) was flushed at the rate of 10 l/min
      for 10 min before irradiation and throughout the entire irradiation procedure. In
      experiment 2, the tumor beds were irradiated at various doses with pions or 250
      KVp photons in 10 fractions over 5 days. In both experiments, the mice were
      observed for 100 days. The rate of tumor appearance was evaluated and the 50%
      tumor control dose (TCD50) calculated. The sensitizing ratio (SR) of N&C obtained
      from the TCD50 assay was 1.46 and the RBE of pions was 1.24. The SR of N&C and
      the RBE of pions were lower for microscopic tumors than those previously reported
      for macroscopic tumors. These results were probably due to the absence or reduced
      presence of radiobiological hypoxic component in the microscopic lesion. However,
      N&C can be considered to provide an advantage for treatment of even clinical
      microscopic tumors.

PMID- 10203597
TI  - Enhancement of antitumor effect of hyperthermia with glucose administration in
      murine mammary carcinoma.
AB  - Antitumor effects of hyperthermia are enhanced by lowering the pH in the tumor
      tissue with administration of glucose. This decreased pH in the tumor tissue with
      glucose administration was determined using mouse experimental tumors. 31P-MRS
      microelectrodes were used for the measurement of pH. By using these two
      measurement methods, time course change in the tumor tissue was determined in the
      controls and the groups treated with 6 g/kg of intraperitoneal glucose. The
      determination of pH with 31P-MRS was calculated from the chemical shift of the
      peak of creatine phosphate (Pcr) and that of inorganic phosphate (Pi). Following
      glucose administration, the tumor tissue showed a decrease of 0.3 pH units with
      the microelectrode method, but did not show any significant decrease in pH with
      the MRS determination. This finding suggested that 31P-MRS showed intracellular
      pH (pHi) due to the localization of Pi and that the microelectrode indicated
      interstitial or extracellular pH (pHe). The ATP/Pi ratio obtained in tumor tissue
      24 h after heat treatment (with, without glucose) was correlated with tumor
      inhibition.

PMID- 10203598
TI  - Loss of heterozygosity of methylenetetrahydrofolate reductase in colon
      carcinomas.
AB  - Folate derivatives are essential for DNA synthesis and methylation. A large
      proportion of the Caucasian population is heterozygous for a common substitution,
      677C-->T (alanine-->valine), in methylenetetrahydrofolate reductase (MTHFR), an
      enzyme of folate interconversion. Homozygous mutant individuals, approximately 10
      15% of North Americans, have been reported to have a reduced risk of colorectal
      cancer. We examined lymphocyte and tumor tissue DNA from colorectal carcinoma
      patients from two different populations to assess loss of heterozygosity (LOH) of
      MTHFR. We observed LOH in approximately 16% of colorectal tumors; in 8 of the 11
      tumors with LOH, the mutant valine allele was lost. Additional studies are
      required to determine if preferential loss of the mutant allele is a common
      finding that could contribute to colorectal tumorigenesis.

PMID- 10203599
TI  - Diffuse bone metastasis with hematologic disorders from gastric cancer:
      clinicopathological features and prognosis.
AB  - Bone metastases diffusely invading the bone marrow from gastric cancer often
      manifest a rapid clinical course and the prognosis is very poor due to
      hematologic disorders such as DIC (disseminated intravascular coagulation) and/or
      MAHA (microangiopathic hemolytic anemia). The objective of this study was to
      clarify the clinicopathological features and prognosis of patients with gastric
      cancer in whom diffuse bone metastasis associated with hematologic disorders were
      evident. Thirty-eight patients with bone metastasis from a primary gastric cancer
      were thus selected and placed into 2 groups consisting of 15 with diffuse bone
      metastasis with DIC and/or MAHA, and 23 patients who had bone metastasis without
      hematological disorders. We compared the clinicopathological features and
      prognosis between the two groups. The clinicopathological features in patients
      with diffuse bone metastasis accompanied by hematologic disorders were
      significantly related to undifferentiated adenocarcinoma, a relatively younger
      age, elevated levels of serum ALP-BI and LDH, and a lower frequency of
      extraosseous metastasis. The median survival time after manifestation was 2 and
      11 months for the patients with or without hematologic disorders, respectively.
      The prognosis was significantly worse in cases of DIC with the median survival
      being only one month. Since, prognosis of diffuse bone metastasis from gastric
      cancer is significantly poor, close attention should be directed to the specific
      clinicopathologic features related to diffuse bone metastasis plus hematologic
      disorders. Regarding high risk patients, a regular follow-up of the serum
      chemistry levels and a bone scan will aid in the early detection of the disease.

PMID- 10203600
TI  - Association of hyaluronidase and breast adenocarcinoma invasiveness.
AB  - Hyaluronic acid (HA) is a component of the extracellular matrix (ECM) that exists
      as a high molecular weight polymer composed of alternating disaccharides, D
      glucuronic acid and N-acetyl D-glucosamine. The interaction of hyaluronidase with
      HA results in the disruption of basement membrane integrity and produces an
      angiogenic response that has been implicated in tumor invasiveness and
      metastasis. Although hyaluronidase is present in several neoplasms, levels of
      hyaluronidase expression in breast cancer are not known. This investigation
      defines the correlation of elevated levels of hyaluronidase with breast
      adenocarcinoma invasiveness. Utilizing RT-PCR, RNA was extracted from paraffin
      embedded tissues (n=6) of patients diagnosed with fibrocystic breast changes,
      ductal carcinoma in situ (DCIS), and invasive adenocarcinoma. After constructing
      cDNA primers for base pairs 504 and 759 of the PH-20 gene (which is homologous to
      the hyaluronidase gene), PCR was performed and the products were visualized with
      ethidium bromide using gel electrophoresis. Invasive breast adenocarcinoma had a
      significantly higher level of hyaluronidase expression compared to other breast
      tissue samples; (32+/-15 vs. 8+/-3; p<0.03). Elevated levels of hyaluronidase
      correlated with invasive breast adenocarcinoma. Our data suggests that elevated
      levels of hyaluronidase are associated with breast adenocarcinoma invasive
      potential. Hyaluronidase may play an integral role in breast cancer invasion and
      metastasis.

PMID- 10203601
TI  - Relationship of urokinase and urokinase receptor in non-small cell lung cancer to
      proliferation, angiogenesis, metastasis and patient survival.
AB  - The purpose of the analysis was to ascertain whether the expression of components
      of the plasminogen activation system possesses an association with several
      biological parameters. The expression of urokinase (uPA) and urokinase receptor
      (uPAR) was analyzed in 137 non-small cell lung carcinomas by
      immunohistochemistry. No relationship could be observed between the proliferative
      activity of the carcinomas measured by flow cytometry and the expressions of uPA
      and uPAR. In addition, there was no association of the expressions of uPA or uPAR
      and vessel density (angiogenesis), neither any significant correlation between
      the expressions of uPA or uPAR and metastasis. The median survival was shorter
      for patients with uPA positive carcinomas than for those with uPA negative tumors
      (60 vs. 111 weeks; p=0.018). The relative risk estimate for patients with uPA
      positive tumors was increased by a factor of 1.8. In contrast, the expression of
      uPAR showed no significant correlation with overall survival.

PMID- 10203602
TI  - Platelet-derived endothelial cell growth factor is not implicated in progression
      of cervical cancer.
AB  - We examined the expression of platelet-derived endothelial cell growth factor (PD
      ECGF) mRNAs in 47 invasive cervical cancer tissues by semi-quantitative RT-PCR
      and addressed its association with clinicopathological features including
      microvessel density. Squamous cell carcinomas expressed higher levels of PD-ECGF
      mRNA than non-squamous cell carcinomas (P=0.014). We found no association between
      FIGO stage and levels of PD-ECGF mRNA. A subset of 31 patients with stage Ib-II
      cervical cancer underwent radical hysterectomy and pelvic lymphadenectomy. There
      were no significant differences in PD-ECGF mRNA levels with respect to tumor
      size, degree of stromal invasion, lymphvascular space involvement, parametrial
      involvement, vaginal involvement or lymph node metastasis among these patients.
      There was no correlation between microvessel density and the levels of PD-ECGF
      mRNA. These findings suggest that PD-ECGF expression is not associated with
      progression and metastasis of cervical cancer.

PMID- 10203603
TI  - Interferon gamma increases the antitumor activity of mitomycin C against human
      colon cancer cells in vitro and in vivo.
AB  - A combined antitumor activity of mitomycin C (MMC) and interferon gamma-1a (IFN
      gamma) was evaluated to be synergistic by the 3-(4, 5-dimethylthiazol-2yl)-2,5
      diphenyl-2H tetrazolium bromide assay and human tumor xenografts/severe combined
      immunodeficient (SCID) mouse system using colon cancer cell lines. The
      experimental metastasis of WiDr cells in SCID mouse was inhibited by MMC and IFN
      gamma with their synergism. Intracellular uptake of MMC in WiDr cells in vitro
      was significantly increased by IFN-gamma, suggesting the mode of synergism of
      these agents. This model may also partly explain the antitumor activity of
      combined MMC, 5-fluorouracil and interleukin-2 treatment on hepatic metastasis of
      colon cancer.

PMID- 10203604
TI  - Growth inhibition of human osteosarcoma HuO9 cells by methylglyoxal
      bis(cyclopentylamidinohydrazone) in vitro and in vivo.
AB  - Polyamines are considered to be important intracellular molecules for the
      proliferation of cancer cells. In this study, effects of methyl-glyoxal
      bis(cyclopentylamidinohydrazone) (MGBCP), a potent inhibitor of the polyamine
      biosynthetic pathway, on the growth of human osteosarcoma HuO9 cells have been
      investigated. MGBCP dose-dependently inhibited the growth of HuO9 cells, in which
      the contents of spermine, spermidine and putrescine decreased concomitantly. The
      MGBCP-treated cells clearly exhibited morphological changes, indicating the
      blebbing and chromatin condensation which are characteristic of apoptosis.
      Characteristic oligonucleosomal-sized DNA fragments were observed in the MGBCP
      treated cells. In in vivo experiments MGBCP (20 or 50 mg/kg) inhibited the growth
      of transplanted HuO9 tumors in mice. These findings suggest that the inhibition
      of polyamine synthesis results in the suppression of growth of osteosarcoma HuO9
      cells, eventually inducing apoptosis in these human osteosarcoma cells in vitro
      and in vivo.

PMID- 10203605
TI  - Combined pre-operative chemotherapy with intra-arterial cisplatin and continuous
      intravenous adriamycin for high grade osteosarcoma.
AB  - Osteosarcoma is one of the most common juvenile malignant tumors in Korea.
      Combined modality treatment (pre-operative chemotherapy + limb salvage surgery +
      adjuvant therapy) improved the patients' overall survival and quality of life. We
      evaluated the efficacy and feasibility of pre-operative chemotherapy with intra
      arterial (IA) cisplatin plus continuous intravenous infusion (CI) of adriamycin.
      We assessed the rate of limb salvage, recurrence pattern and the survival impact
      based on the histologic response of pre-operative chemotherapy. Fourty-one
      patients with histologically-proven high grade osteosarcoma of the extremities
      were enrolled from January 1990 to June 1995. Pre-operative chemotherapy,
      cisplatin 120 mg/m2 IA and adriamycin 75 mg/m2/72 h CI was administered every 3
      weeks for 3 cycles, followed by limb salvage surgery if possible or by
      amputation. According to the histologic tumor response, if the tumor necrosis was
      >90%, the same regimen was administered for 3 cycles as an adjuvant therapy. A
      salvage regimen (Ifosfamide 7.5 gm/m2/5 d IV + high dose MTX 10 gm/m2 IV+VP-16
      360 mg/m2/3 d IV) was administered every 3 weeks for 6 cycles if the tumor
      necrosis was <90%. Of 41 patients, 37 patients were evaluable for efficacy and
      toxicities, because 4 patients refused chemotherapy after 1 or 2 cycles. Twenty
      one patients were male and 16 were female with median age of 16 years (range 8
      41). The tumor locations were: distal femur 20, proximal tibia 8, humerus 6,
      distal tibia 2 and 1 in proximal femur. All but one patient, who died of
      neutropenic sepsis, completed the planned pre-operative therapy. Of the 36
      patients who received surgery, limb salvage surgery was possible in 30 patients
      (83.3%) and 27 patients (75%) showed a good response (grade III 10; 27.8%, grade
      IV 17; 47.2%). With a median follow-up of 23 months, 3-year disease-free survival
      rate was 54.7% and overall survival rate was 78.3%. Of the 15 patients who
      recurred, the major metastatic site was the lung. No operation-related mortality
      was observed. Most patients experienced grade III-IV nausea, vomiting and
      hematologic toxicities, which were reversible with supportive cares. Pre
      operative chemotherapy with IA DDP+CI ADR followed by surgery showed 75%
      histologic tumor response rate, 83% limb salvage rate and 54.7% 3-year disease
      free survival rate with tolerable side effects. To improve the survival rate, the
      possible role of good salvage chemotherapy with a non-cross resistance regimen in
      poor responders should be evaluated.

PMID- 10203606
TI  - Expression of type I interferon receptor in renal cell carcinoma.
AB  - Immunohistochemical analysis of INF-R was performed on 110 renal tumors, 25
      peritumoral kidney tissues and 10 lymph node metastases. Pathological material
      was previously studied and classified according to predominant cell type, stage
      and grade. A statistical analysis was made in order to determine to what extent
      the immunoexpression of INF-R differed in relation to the histological variables
      studied. All peritumoral kidney sections, 89/110 tumors and 9/10 metastases
      proved positive. Membranous expression was related to clear cell carcinomas. Type
      I INF-R is expressed in RCC, independent of tumor stage and grade, as well as
      sex, age and survival. INF-R is widely expressed in RCC in any tumoral type, and
      its expression is preserved in metastatic disease, which may help to target those
      patients who could benefit from INF therapy.

PMID- 10203607
TI  - Pilot study of combined treatment with continuous infusion of 5-fluorouracil,
      mitomycin C, and cisplatin (FMP) in patients with inoperable advanced gastric
      cancer.
AB  - We investigated combined chemotherapy with 5-fluorouracil (600 mg/m2/day, day 1
      5, c.i.v.), mitomycin-C (6 mg/m2, day 6), and cisplatin (60 mg/m2, day 7) for
      inoperable advanced gastric cancer, including those with poor performance status
      (PS). Overall response rates were 62.5% (20/32), 59.1% (12/22) for PS 0-2 and
      70.0% (7/10) for PS 3-4. Median survival was 7.2 months, 8.7 for PS 0-2; and 6.3
      for PS 3-4. There was no serious toxicity or any treatment-related death. This
      therapy is useful, even for poor PS.

PMID- 10203608
TI  - Lack of gene amplification as a mechanism of CDK4 activation in human
      neuroblastoma.
AB  - Neuroblastoma is the most frequent solid tumor in childhood. We have analysed 48
      neuroblastomas of different stages and degrees of cellular differentiation for
      CDK4 amplification by a fluorescent differential PCR assay. We explored the
      relative densitometric measure of a 119 bp fragment of the CDK4 gene versus an 82
      bp fragment of the IFNG gene. We were not able to detect any case of CDK4 gene
      amplification in the neuroblastomas. In conclusion, CDK4 activation does not seem
      to be relevant to the development of neuroblastomas, at least through gene
      amplification.

PMID- 10203609
TI  - Primary non-Hodgkin's lymphoma of the female genital tract.
AB  - Genital tract lymphoma is a rare disease; information on diagnosis, treatment and
      outcome are limited. We report on eight patients affected by non-Hodgkin's
      lymphoma of the genital tract, five from the cervix, two from the vagina and one
      from the vulva collected between 1987 and 1998. Age at presentation ranged from
      36 to 82 (median 67) years. The commonest initial symptom was vaginal bleeding,
      post coital in 1 patient. Three patients complained of vescical symptoms. Ann
      Arbor classification was stage IAE for 6 patients. Histology, according to the
      IWF, was either intermediate grade (4 patients), or high grade (3 patients), not
      evaluable in one case. Seven patients were treated with chemotherapy
      (anthracycline based in four) followed by pelvic radiotherapy in five; one
      patient received irradiation alone. Five patients are currently alive and free of
      disease with follow-up ranging from 8 to 126 months. Based on our experience in
      this series, we support a management scheme of combination chemotherapy and
      radiotherapy for patients with non-Hodgkin's lymphoma of the genital tract.

PMID- 10203611
TI  - Technetium-99m methylene diphosphonate scintimammography for evaluation of
      palpable breast masses.
AB  - Technetium-99m-methylene diphosphonate (Tc-99m MDP) scintimammography (SMB) was
      used to investigate palpable breast masses during routine presurgical bone
      scintigraphy, for women at high risk for cancer and who were candidates for
      surgery or excisional biopsy. Upright anterior and prone lateral views of the
      breasts were acquired from 65 women with palpable breast masses, 5-10 min after
      intravenous injection of 740 MBq of Tc-99m MDP. Breast cancer was histologically
      diagnosed in 50 women (77%) and benign disease was found in 15 women (23%). Of
      these 50 breast cancer patients, 44 (88%) showed abnormal MDP uptake in breasts.
      Among the 15 cases of benign lesions, only 1 (7%) showed abnormal MDP uptake in
      the breasts. The diagnostic sensitivity, specificity, and accuracy were 88%, 93%,
      and 89%, respectively, for the differentiation of malignant and benign breast
      masses. Scintimammography with Tc-99m MDP is a useful and cost-effective tool for
      differentiating malignant breast masses from benign breast masses.

PMID- 10203610
TI  - Loss of heterozygosity at the ATM locus in colorectal carcinoma.
AB  - Patients homozygous for mutation of the ATM gene exhibit constitutional genetic
      instability and have a high risk of cancer. A-T heterozygotes also have an
      increased tendency to develop adenocarcinomas. Colorectal cancer (CRC) is the
      second most common cancer in western populations, and tumors of the right colon
      are typically highly genetically unstable. The DNA mismatch repair genes mutated
      in most familial and some sporadic CRCs account for one route by which cells
      acquire additional oncogenic mutations during the progression of malignancy.
      Mismatch repair defects, however, do not seem to account for the majority of
      CRCs. Because of its role in maintaining genomic stability, and the high risk of
      cancer to homozygotes, ATM is a candidate gene for inactivation in the evolution
      of chromosomal instability in tumor cells. We have examined 114 CRC patients for
      loss of heterozygosity (LOH) using six microsatellite markers tightly linked to
      the ATM locus. Our data suggest that LOH of this region is not associated with
      cancer of the proximal colon. In the distal colon, LOH was found in 23-31% of
      cases, which is moderately elevated above the non-specific LOH reported in tumors
      of this tissue. No correlations were found with regard to clinicopathological
      variables aside from tumor location.

PMID- 10203612
TI  - A malignancy work-up in patients with cancer-associated (paraneoplastic)
      autoimmune diseases: pemphigus and myasthenic syndromes as cases in point
      (review).
AB  - Although some autoimmune diseases are known to be associated with a higher
      incidence of cancers, they are not usually considered as paraneoplastic diseases,
      but rather as autoimmune diseases that may be neoplasia-associated, since
      currently it is not known whether the tumor leads to their development, or
      alternatively another underlying condition turns the patients prone to both
      cancer and autoimmunity. We review the association of cancer with pemphigus,
      paraneoplastic pemphigus, myasthenia gravis and Eaton-Lambert syndrome, and
      discuss the importance of looking for an occult malignancy in a patient with a
      newly-diagnosed autoimmune disease that is known to be associated with cancer.

PMID- 10203613
TI  - CD80 and IL-2 signals cooperate in the regression of tumors transplanted in
      congenitally athymic mice.
AB  - Interleukin-2 and CD80 transfectants of a methylcholanthrene-induced murine
      sarcoma Mc12 (Mc12-IL-2 and Mc12-CD80 cells) with similar tumorigenicity in
      euthymic mice were utilized for experiments designed to investigate a co
      stimulatory role of the CD80 molecule in allogeneic, congenitally athymic (nu/nu)
      mice. The CD80-transfected cells were as tumorigenic in nu/nu mice as the
      parental Mc12 sarcoma. The IL-2-transfected cells grew only transiently and
      regressed in all nu/nu recipients during four weeks after challenge with doses up
      to 5x10(7) cells. The 1:1 mixture of parental Mc12 with Mc12-CD80 cells grew
      progressively in all inoculated nu/nu mice; in a 1:1 mixture with parental Mc12
      cells, Mc12-IL-2 cells were able to cause regressions in approximately 50% of
      nu/nu mice; the 1:1 mixture of Mc12-IL-2 and Mc12-CD80 transfectants showed only
      transient growth and regressed during four weeks in all inoculated nu/nu mice.
      Adoptive transfer of cell-mediated immunity revealed that spleen cells from tumor
      regressors were capable of transferring the resistance to Mc12 tumor in nu/nu
      mice. The spleen cells from tumor regressors were not cytolytic when allowed to
      react in vitro with Mc12, Mc12-IL-2, or Mc12-CD80 target cells. However, when
      grown in IL-2-containing medium, splenocytes from tumor regressors, but not the
      splenocytes from tumor progressors, could develop cytolytic activity directed
      against Mc12 target cells that was comparable to that of the splenocytes from
      tumor-free controls. These results suggest that the rejection of tumors in nu/nu
      mice was mediated by IL-2-dependent mechanisms in which the CD80 molecule played
      a co-stimulatory role; the results also indicate that the ability to be activated
      by IL-2 and to give rise to cytolytic activity of nu/nu splenocytes from tumor
      progressors is decreased.

PMID- 10203614
TI  - Usefulness of p53 protein, Bcl-2 protein and Ki-67 as predictors of
      chemosensitivity of malignant tumors.
AB  - In various types of human malignant tumors, the presence or absence of expression
      of apoptosis-associated gene products (p53 protein and Bcl-2 protein) and the
      tumor proliferation activity-related factor (Ki-67) was assessed by
      immunohistochemical staining and the correlation between this expression and
      chemosensitivity to anticancer drugs was investigated. Study subjects comprised
      55 preoperative patients with untreated malignant tumors (9 with esophageal
      cancer, 11 with stomach cancer, 11 with colon cancer, 13 with hepatic cancer and
      11 with breast cancer). A chemosensitivity test was carried out with the
      histoculture drug response assay (HDRA) method using 4 drugs, mitomycin C (MMC),
      5-fluorouracil (5-FU), doxorubicin hydrochloride (ADM), and cisplatin (CDDP).
      Immunohistochemical staining was used to assess expression of p53 protein, Bcl-2
      protein and Ki-67. The tumor growth inhibition index (I.I.) of the 4 drugs was
      significantly lower in a group of the patients with p53 protein overexpression
      type (mutant p53 protein positive expression-type) tumors than in a group with
      p53 protein negative expression-type tumors (p<0.05). No significant correlation
      was found between the expression of the Bcl-2 protein by and the I.I. of any drug
      studied in any type of cancer. A negative correlation was found between the
      labeling index (L.I.) for Ki-67 in all cases and I.I. for MMC and ADM and thus,
      chemosensitivity of the tumors with high growth activity was lower. Furthermore,
      a positive correlation existed between the L.I. for Ki-67 and that for p53
      protein. The patients with p53 protein overexpression-type (mutant p53 protein
      positive) tumors showed low chemosensitivity. In addition, overexpression of p53
      protein is suggested to be one of the factors involved in the lowered
      chemosensitivity of the tumors with high growth activity. Summarizing these
      findings, the p53 protein can play an important role in cancer therapy.

PMID- 10203615
TI  - Efficacy of all-trans retinoic acid for molecular relapse of acute promyelocytic
      leukemia during remission.
AB  - We analyzed the efficacy of all-trans retinoic acid (ATRA) as an early treatment
      for four acute promyelocytic leukemia (APL) patients in remission who were
      PML/RARalpha-positive by reverse transcription-polymerase chain reaction or
      fluorescence in situ hybridization. ATRA 45 mg/m2 was administered orally. All
      became negative for PML/RARalpha transcripts after 3 to 6 months of ATRA
      treatment. However, the PML/RARalpha transcripts subsequently reverted to
      positive in three cases. Although retreatment with ATRA failed to prevent
      hematological relapse in two patients, one case remains in hematological
      remission. No serious side effects were encountered during ATRA treatment. These
      findings suggest that early treatment of ATRA for PML/RARalpha-positive APL
      patients in remission may have a therapeutic benefit and prolong the duration of
      hematological remission without chemotherapy.

PMID- 10203616
TI  - Prognostic value of p27Kip1 and p21WAF/Cip protein expression in muscle invasive
      bladder cancer.
AB  - Two genes, namely p27Kip1 and p21WAF/Cip1 that reveal distinct structural
      homology, have been identified as inductors of cell cycle arrest at the G1
      checkpoint to prevent entry of somatic cells into the S phase of the cell cycle
      when substantial DNA damage has occurred. It was demonstrated that the
      p21WAF/Cip1 gene is induced by pathways dependent and independent from a
      functionally intact p53 tumour suppressor protein. It has been suggested that
      decreased expression both of the p21WAF/Cip1 and p27Kip1 protein may contribute
      to the development of human malignancies due to loss of critical
      antiproliferative mechanisms. So far, the role of altered p21WAF/Cip1 and mainly
      of a decreased p27Kip1 protein expression in patients with muscle invasive
      bladder cancer has not been investigated. In the present study, 50 tumour
      specimens from 50 patients undergoing radical cystectomy (T2-T4) were
      investigated for different biological and clinical characteristics as possible
      prognostic factors: age, depth of tumour infiltration (T-stage), histological
      grading (G), lymph node status as well as immunohistochemical staining for the
      p21WAF/Cip1 and p27Kip1 proteins. The median recurrence-free survival for
      patients with and without retained p21WAF/Cip1 protein expression was 54 months
      (3-86 months) and 13 months (1-40 months), respectively (p=0.07). During
      univariate analysis, loss of p21WAF/Cip1 protein expression (p=0.02), T-stage
      (p=0.02) and histological grading (p=0.03) were significant prognostic factors
      for survival, among which a negative reaction for the p21WAF/Cip1 protein
      (p=0.02) as well as T-stage (p=0.005) remained independent significant predictors
      during multivariate analysis. Loss of p27Kip1 protein expression was not
      correlated with the recurrence-free or the overall survival of the patients.
      Prospective studies are needed to confirm the independent prognostic potential of
      cell-cycle associated proteins such as p21WAF/Cip1 in patients with muscle
      invasive bladder cancer. The availability of more refined prognostic factors
      should assist decision making regarding the value of more aggressive treatment
      options, such as adjuvant or neoadjuvant chemotherapy, for defined subgroups of
      patients.

PMID- 10203617
TI  - Clinical utility of chromosome 17 alpha satellite probe in distinguishing benign
      mesothelium from malignant cells: a pilot study using routinely fixed specimens.
AB  - Fluorescent in situ hybridization has shown promise in detecting malignant cells
      in body cavity effusions. However, this requires special preparatory techniques
      not used in many laboratories. We developed an in situ hybridization (ISH)
      procedure specifically for ethanol-fixed specimens, and using it tested the
      clinical utility of the chromosome 17alpha satellite probe (C17alpha). ISH with
      C17alpha was used in 12 malignant and 10 benign ethanol-fixed body cavity
      effusions. Cells were pretreated with protease K prior to ISH. The probe was
      detected by an anti-digoxigenin-horseradish peroxidase method. Signals were
      counted in 100 nuclei and the chromosome index (CI) and percent diploid cells
      calculated in each case. ISH was successfully performed in all cases. Malignant
      cells had an average CI of 2.23 with less than 44% diploid nuclei and 50% of
      specimens exhibited bizarre signals. Benign effusions had an average CI of 1.98
      with over 84.6% diploid nuclei. Questionably bizarre signals were seen in two
      (20%) benign specimens. ISH can be performed on ethanol-fixed specimens. The
      C17alpha probe may prove valuable in detecting malignant cells in body cavity
      effusions.

PMID- 10203618
TI  - Clinical and biological characteristics of breast cancers in post-menopausal
      women receiving hormone replacement therapy for menopause.
AB  - The paradox of an excess breast cancer incidence among current users of hormone
      replacement therapy (HRT) without excess in breast cancer mortality raises the
      question of possible differences in the clinical and biological characteristics
      of cancers in current HRT users compared to non-users. A consecutive series of
      129 post-menopausal patients under HRT for at least 6 months, in whom an operable
      breast cancer was diagnosed from January 1992 to December 1996, were identified
      retrospectively. In most cases women had received combination HRT (estrogen and
      progestative) and the mean duration was 60.4 (range: 6-360) months. Breast
      cancers diagnosed in post-menopausal patients during 1992-1993 at the Institut
      Curie constituted the reference series. Cancers in patients receiving HRT were
      smaller: 78% versus 32% T1 and 12 mm in larger diameter versus 29.5 mm. They were
      also more often diagnosed radiologically (49 versus 33%). A second group of 420
      post-menopausal breast cancer patients whose samples had been referred for
      steroid hormone receptor and flow cytometric analysis in 1992-1996 were used for
      comparing biological and pathological information. Cancers of patients receiving
      HRT tended to be more often grade I and rarely grade III in the Scarf Bloom
      Richardson classification. Percentage of cells in S-phase as measured by flow
      cytometry was considerably lower in HRT users compared to control (mean 2.4
      versus 3.7, median 2.2 versus 2. 6). Lymph node invasion, ploidy, and steroid
      hormone receptor expression did not differ significantly between the 2 groups.
      This apparently more favourable phenotype of breast cancers diagnosed in post
      menopausal patients receiving HRT compared to unselected non-HRT users was not
      confirmed when analysis was restricted to breast cancers of less than 25 mm in
      diameter. If, as expected, the phenotypic information bears out in terms of
      prognosis, this may contribute to overcome the reticence in prescribing HRT due
      to the increased risk of breast cancer. However, it is still not clear whether
      the biologically less aggressive phenotype is related to the hormone treatment or
      is simply due to early detection.

PMID- 10203619
TI  - Using feedback letters to influence the use of antiulcer agents in a Medicaid
      program.
AB  - OBJECTIVE: To determine the impact of printed patient-specific feedback regarding
      potential misprescribing of antiulcer agents (AUAs). Measures of impact included
      improvements in patients' dispensing profiles, assessed according to
      predetermined criteria, and decreases in cost and quantity of AUAs dispensed.
      DESIGN: Controlled study. After evaluation for compliance with predetermined
      criteria, prescribers identified as having one or two patient profiles with
      potential errors were assigned alternatively to control or experimental groups.
      An intervention was mailed to the experimental group. SETTING: Outpatient setting
      in the New Mexico Medicaid population. PARTICIPANTS: Patients and prescribers
      identified as having potential misprescribing of AUAs. INTERVENTION: The
      intervention consisted of a cover letter describing the purpose of the drug
      utilization review program, an educational fact sheet regarding prescribing AUAs,
      patient profiles with potential misprescribing, and physician response forms.
      MEASUREMENTS AND MAIN RESULTS: There were greater improvements in dispensing to
      patients in the intervention group (chi2, p <.001). Significant odds ratios for
      the intervention group were 2.29 for AUAs discontinued, 1.98 for all improvements
      combined, 13.13 for improvement in listing of proper diagnosis for AUAs, and 2.84
      for appropriate indication when prescribing the higher acute daily dosage. Using
      data from 3 months before and after the intervention, we found greater decreases
      in mean monthly costs (p =.044) and mean monthly quantity of AUAs dispensed (p
      =.049) in the intervention group. CONCLUSIONS: This intervention significantly
      decreased AUA dispensing to patients whose prescribers were mailed the patient
      specific feedback intervention.

PMID- 10203621
TI  - Marital and parental satisfaction of married physicians with children.
AB  - OBJECTIVE: To evaluate personal and professional factors associated with marital
      and parental satisfaction of physicians. STUDY DESIGN: Cross-sectional study.
      PARTICIPANTS: A survey was sent to equal numbers of licensed male and female
      physicians in a Southern California county. Of 964 delivered questionnaires, 656
      (68%) were returned completed. Our sample includes 415 currently married
      physicians with children, 64% male and 36% female. MEASUREMENTS AND MAIN RESULTS:
      Ratings of marital and parental satisfaction were measured on a 5-point Likert
      scale, 5 being extremely satisfied. Prevalence of work and home life factors was
      also evaluated. The mean score for marital satisfaction was 3.92 (range 1.75
      5.0). Approximately half of the physicians reported high levels of marital
      satisfaction (63% of male physicians and 45% of female physicians). The gender
      difference disappeared after adjusting for age differences. Two factors were
      associated with high marital satisfaction: a supportive spouse (odds ratio [OR]
      10.37; 95% confidence interval [CI] 2.66, 40.08) and role conflict (OR 0.61; 95%
      CI 0.42, 0.88). The mean score for parental satisfaction was 3. 43 (range 1.0
      5.0), and approximately two thirds of both male and female physicians reported at
      least moderate levels of parental satisfaction. The major factors associated with
      parental satisfaction were a supportive spouse (OR 2.24; 95% CI 1.32, 3.80), role
      conflict (OR 0.35; 95% CI 0.23, 0.53), salaried practice setting (OR 2.14; 95% CI
      1.21, 3.81), marriage to a spouse working in a profession (OR 2.14; 95% CI 1.21,
      3.81), and marriage to a spouse working as a homemaker (OR 2.33; 95% CI 1.20,
      4.56). Number of hours worked was not found to be related to either satisfaction
      score, but rather to an intervening variable, role conflict. CONCLUSIONS: For
      physicians with children, our study indicates that minimizing the level of role
      conflict and having a supportive spouse are associated with higher levels of
      marital and parental satisfaction. Working in salaried positions and marriage to
      a spouse who is either working in a profession or who is a stay-at-home parent
      are also related to high parental satisfaction.

PMID- 10203620
TI  - The relation between purulent manifestations and antibiotic treatment of upper
      respiratory tract infections.
AB  - OBJECTIVE: To describe the clinical features of patients diagnosed with upper
      respiratory tract infections (URIs), and determine which clinical features are
      associated with antibiotic use. DESIGN: Prospective cohort study. SETTING: Three
      ambulatory care practices at a group-model HMO in the Denver metropolitan area.
      PATIENTS: Adults (aged 18 years or older) seeking care for acute respiratory
      illnesses. MEASUREMENTS: Clinical features were documented on standardized
      encounter forms. Clinician type, secondary diagnoses, and antibiotic treatment
      were extracted from administrative databases. Results are presented as adjusted
      odds ratios (ORs) with 95% confidence intervals (CIs). MAIN RESULTS: Antibiotics
      were prescribed to 33% (95% CI 28%, 38%) of patients diagnosed with URI, after
      excluding patients with coexisting antibiotic-responsive conditions (e.g.,
      sinusitis, pharyngitis) or a history of cardiopulmonary disease. Multivariate
      logistic regression analysis identified tobacco use (OR 2.8; 95% CI 1.5, 5.1),
      history of purulent nasal discharge (OR 2.0; 95% CI 1.1, 3.6) or green phlegm (OR
      4.8; 95% CI 2.1, 11.1), and examination findings of purulent nasal discharge (OR
      5.2; 95% CI 2.4, 11.2) or tonsillar exudate (OR 3.7; 95% CI 1.1, 12.1) to be
      independently associated with antibiotic use. The majority of patients treated
      with antibiotics (82%) had at least one of these factors present. CONCLUSIONS:
      Antibiotic treatment of URIs is most common when purulent manifestations are
      present. Efforts to reduce antibiotic treatment of URIs should educate clinicians
      about the limited value of purulent manifestations in predicting antibiotic
      responsive disease.

PMID- 10203622
TI  - Impact of new guidelines on physicians' ordering of preoperative tests.
AB  - OBJECTIVE: To compare the number of preoperative tests ordered for elective
      ambulatory surgery patients during the 2 years before and the 2 years after the
      establishment of new hospital testing guidelines. MEASUREMENTS: The patterns of
      preoperative testing by surgeons and a medical consultant during the 2 years
      before and the 2 years after the establishment of new guidelines at one
      orthopedic hospital were reviewed. All tests ordered preoperatively were
      determined by review of medical records. Preoperative medical histories, physical
      examinations, and comorbidities were obtained according to a protocol by the
      medical consultant (author). Perioperative complications were determined by
      review of intraoperative and postoperative events, which also were recorded
      according to a protocol. MAIN RESULTS: A total of 640 patients were enrolled, 361
      before and 279 after the new guidelines. The mean number of tests decreased from
      8.0 before to 5.6 after the new guidelines ( p =.0001) and the percentage
      decrease for individual tests varied from 23% to 44%. Except for patients with
      more comorbidity and patients receiving general anesthesia, there were decreases
      across all patient groups. In multivariate analyses only time of surgery (before
      or after new guidelines), age, and type of surgery remained statistically
      significant ( p =.0001 for all comparisons). Despite decreases in surgeons'
      ordering of tests, the medical consultant did not order more tests after the new
      guidelines ( p =.60) The majority of patients had no untoward events
      intraoperatively and postoperatively throughout the study period, with only 6%
      overall requiring admission to the hospital after surgery, mainly for reasons not
      related to abnormal tests. Savings from charges totaled $34,000 for the patients
      in the study. CONCLUSIONS: Although there was variable compliance among
      physicians, new hospital guidelines were effective in reducing preoperative
      testing and did not result in increases in untoward perioperative events or in
      test ordering by the medical consultant.

PMID- 10203623
TI  - Leg symptoms, the ankle-brachial index, and walking ability in patients with
      peripheral arterial disease.
AB  - OBJECTIVE: To determine how functional status and walking ability are related to
      both severity of lower extremity peripheral arterial disease (PAD) and PAD
      related leg symptoms. DESIGN: Cross-sectional study. SETTING: Academic medical
      center. PARTICIPANTS: Patients aged 55 years and older diagnosed with PAD in a
      blood flow laboratory or general medicine practice (n = 147). Randomly selected
      control patients without PAD were identified in a general medicine practice (n =
      67). MEASUREMENTS: Severity of PAD was measured with the ankle-brachial index
      (ABI). All patients were categorized according to whether they had (1) no
      exertional leg symptoms; (2) classic intermittent claudication; (3) exertional
      leg symptoms that also begin at rest (pain at rest), or (4) exertional leg
      symptoms other than intermittent claudication or pain at rest (atypical
      exertional leg symptoms). Participants completed the 36-Item Short-Form Health
      Survey (SF-36) and the Walking Impairment Questionnaire (WIQ). The WIQ quantifies
      patient-reported walking speed, walking distance, and stair-climbing ability,
      respectively, on a scale of 0 to 100 (100 = best). MAIN RESULTS: In multivariate
      analyses patients with atypical exertional leg symptoms, intermittent
      claudication, and pain at rest, respectively, had progressively poorer scores for
      walking distance, walking speed, and stair climbing. The ABI was measurably and
      independently associated with walking distance (regression coefficient = 2.87/0.1
      ABI unit, p =.002) and walking speed (regression coefficient = 2.09/0.1 ABI unit,
      p =.015) scores. Among PAD patients only, pain at rest was associated
      independently with all WIQ scores and six SF-36 domains, while ABI was an
      independent predictor of WIQ distance score. CONCLUSIONS: Both PAD-related leg
      symptoms and ABI predict patient-perceived walking ability in PAD.

PMID- 10203624
TI  - Hospitalists and 'officists' preparing for the future of general internal
      medicine.

PMID- 10203625
TI  - Validation of a Trauma Questionnaire in veteran women.
AB  - The Trauma Questionnaire (TQ) assesses a woman's history of childhood and adult
      sexual trauma, sexual harassment, and domestic violence. The TQ is used widely at
      Veterans Affairs Medical Centers, but its validity has not been thoroughly
      examined. In a prospective study of 127 women, we found the TQ to have good to
      excellent agreement with a semistructured clinician interview and good
      sensitivity and specificity. The TQ can be used as a valid alternative to the
      clinician interview in the initial elicitation of trauma history among women
      veterans in the primary care setting.

PMID- 10203626
TI  - The timing of do-not-resuscitate orders and hospital costs.
AB  - The relation between the timing of do-not-resuscitate (DNR) orders and the cost
      of medical care is not well understood. This prospective observational study
      compares hospital costs and length of stay of 265 terminally ill patients with
      admission DNR orders, delayed DNR orders (occurring after 24 hours), or no DNR
      orders (full code). Patients whose orders remained full code throughout a
      hospital stay had similar lengths of stay, total hospital costs, and daily costs
      as patients with admission DNR orders. Patients with delayed DNR orders, by
      contrast, had a greater mortality, longer length of stay, and higher total costs
      than full code or admission DNR patients, but similar daily costs. The causes of
      delay in DNR orders and the associated higher costs are a matter for future
      research.

PMID- 10203628
TI  - Comparing ambulatory preceptors' and students' perceptions of educational
      planning.
AB  - To compare ambulatory preceptors' and students' perceptions of the use of
      educational planning (setting goals, assessing needs, formulating objectives,
      choosing methods, and providing feedback and evaluation) in the office setting,
      we mailed a survey, which was returned by 127 longitudinal ambulatory preceptors
      and 168 first-year and second-year medical students. Faculty perceptions did not
      match student perceptions of what occurred in the longitudinal preceptor program
      teaching sessions in educational planning areas. Students perceived these
      activities were occurring with much less frequency than faculty perceived.
      Medical education needs to move beyond the usual faculty development workshop
      paradigm to a more comprehensive educational development model that includes
      training both faculty and students in core educational skills. This will enable
      the ambulatory setting to reach its full educational potential in training future
      physicians.

PMID- 10203627
TI  - Willingness to pay for diagnostic certainty: comparing patients, physicians, and
      managed care executives.
AB  - Cost-effectiveness analyses routinely ignore the value of diagnostic certainty.
      Moreover, no previous study has compared this value among different stakeholders.
      We surveyed 25 patients, 28 physicians, and 23 managed care executives to compare
      their willingness to pay for diagnostic information for peptic ulcer disease.
      Patients (84%) were most likely, and executives (43%) least likely, to be willing
      to pay at least $1 (median willingness to pay < $50). Differences in willingness
      to pay among stakeholders indicate potential for conflicts over access to tests.
      Although nearly all patients valued diagnostic certainty, its value was generally
      small and insufficient to change the cost-effectiveness ranking of treatment
      alternatives.

PMID- 10203629
TI  - Medical editors, journal owners, and the sacking of George Lundberg.

PMID- 10203630
TI  - Managing upper respiratory tract infections: practice without evidence.

PMID- 10203631
TI  - Specialization by practice location.

PMID- 10203632
TI  - Experiences and attitudes of residents and students influence voluntary service
      with homeless populations.
AB  - OBJECTIVE: To assess the impact of two programs at the University of Pittsburgh,
      one that requires and one that encourages volunteer activity. In the program that
      requires primary care interns to spend 15 hours in a homeless clinic, we measured
      volunteer service after the requirement was fulfilled. In the program that
      encourages and provides the structure for first- and second-year medical students
      to volunteer, we assessed correlates of volunteering. MEASUREMENTS AND MAIN
      RESULTS: When primary care interns were required to spend time at homeless
      clinics, all (13/13) volunteered to work at the same clinic in subsequent years.
      Categorical interns without this requirement were less likely to volunteer
      (24/51; chi2 = 12.7, p >. 001). Medical students who volunteered were more likely
      to be first-year students, have previously volunteered in a similar setting, have
      positive attitudes toward caring for indigent patients, and have fewer factors
      that discouraged them from volunteering (p <. 01 for all) than students who did
      not volunteer. CONCLUSIONS: Volunteering with underserved communities during
      medical school and residency is influenced by previous experiences and, among
      medical students, year in school. Medical schools and residency programs have the
      opportunity to promote volunteerism and social responsibility through mentoring
      and curricular initiatives.

PMID- 10203633
TI  - Racial differences in patients' perceptions of debilitated health states.
AB  - OBJECTIVE: To determine health utility scores for specific debilitated health
      states and to identify whether race or other demographic differences predict
      significant variation in these utility scores. DESIGN: Utility analysis. SETTING:
      A community hospital general internal medicine clinic, a private internal
      medicine practice, and a private pulmonary medicine practice. PARTICIPANTS: Sixty
      four consecutive patients aged 50 to 75 years awaiting appointments. In order to
      participate, patients at the pulmonary clinic had to meet prespecified criteria
      of breathing impairment. MEASUREMENTS: Individuals' strength of preference
      concerning specific states of limited physical function as measured by the
      standard gamble technique. MAIN RESULTS: Mean utility scores used to quantitate
      limitations in physical function were extremely low. Using a scale for which 0
      represented death and 1.0 represented normal health, limitation in activities of
      daily living was rated 0. 19 (95% confidence interval [CI] 0.13, 0.25), tolerance
      of only bed-to-chair ambulation 0.17 (95% CI 0.11, 0.23), and permanent nursing
      home placement 0.16 (95% CI 0.10, 0.22). Bivariate analysis identified female
      gender and African-American race as predictors of higher utility scores ( p
      </=.05). In multiple regression analysis, only race remained statistically
      significant ( p </=.02 for all three outcome variables). CONCLUSION: Comparisons
      of African-American values with those of whites concerning defined states of
      debility demonstrate greater than threefold increases in utility scores. This
      finding suggests that racial differences need to be taken into account when
      studying the effects of medical interventions on quality of life.

PMID- 10203634
TI  - The role of patients and providers in the timing of follow-up visits. Telephone
      Care Study Group.
AB  - OBJECTIVE: Although the decision about how frequently to see outpatients has a
      direct impact on a provider's workload and may impact health care costs, revisit
      intervals have rarely been a topic of investigation. To begin to understand what
      factors are correlated with this decision, we examined baseline data from a
      Department of Veterans Affairs (VA) Cooperative Study designed to evaluate
      telephone care. DESIGN: Observational study based on extensive patient data
      collected during enrollment into the randomized trial. Providers were required to
      recommend a revisit interval (e.g., "return visit in 3 months") for each patient
      before randomization, under the assumption that the patient would be receiving
      clinic visits as usual. POPULATION/SETTING: Five hundred seventy-one patients
      over age 55 cared for by one of the 30 providers working in three VA general
      medical clinics. Patients for whom immediate follow-up (</=2 weeks) was
      recommended were excluded. MEASUREMENTS: Mean revisit interval was adjusted for
      patient factors using a regression model that accounted for patients being nested
      within providers and providers being nested within sites. Four patient-level
      variable blocks (illness burden-patient, travel time, illness burden-physician,
      and prior utilization) were sequentially entered into a linear model to determine
      their role in explaining the variance in revisit intervals. Physician identity
      was also entered after four blocks. MAIN RESULTS: Recommended revisit intervals
      ranged from 1 month to over 1 year with the most common recommended intervals
      being 2, 3, or 6 months. About 10% of the variance in revisit interval was
      explained by illness measures independent of provider (e.g., general health
      perception) and travel time. Adding other illness measures (e.g., diagnoses,
      medications) and prior utilization (e.g., clinic visits) doubled the variance
      explained (R2 =.21). Finally, the identification of individual provider doubled
      the explained variance again (R2 =.45). After adjusting for patient factors, the
      average revisit interval for individual providers ranged from 8 to 26 weeks (8 to
      19 weeks when restricted to the 16 staff physicians). There were also substantial
      differences across the three sites (adjusted means: 14, 17, and 11 weeks).
      CONCLUSIONS: Even after adjusting for a detailed array of patient-level data,
      primary care providers have different practice styles regarding the timing of
      return visits. These may, in turn, reflect the local "culture" in which they
      practice. How many patients providers are able to care for may be determined by
      the providers' inclinations toward the timing of follow-up visits.

PMID- 10203635
TI  - Setting the revisit interval in primary care.
AB  - OBJECTIVE: Although longitudinal care constitutes the bulk of primary care,
      physicians receive little guidance on the fundamental question of how to time
      follow-up visits. We sought to identify important predictors of the revisit
      interval and to describe the variability in how physicians set these intervals
      when caring for patients with common medical conditions. DESIGN: Cross-sectional
      survey of physicians performed at the end of office visits for consecutive
      patients with hypertension, angina, diabetes, or musculoskeletal pain.
      PARTICIPANTS/SETTING: One hundred sixty-four patients under the care of 11
      primary care physicians in the Dartmouth Primary Care Cooperative Research
      Network. MEASUREMENTS: The main outcome measures were the variability in mean
      revisit intervals across physicians and the proportion of explained variance by
      potential determinants of revisit intervals. We assessed the relation between the
      revisit interval (dependent variable) and three groups of independent variables,
      patient characteristics (e.g., age, physician perception of patient health),
      identification of individual physician, and physician characterization of the
      visit (e. g., routine visit, visit requiring a change in management, or visit
      occurring on a "hectic" day), using multiple regression that accounted for the
      natural grouping of patients within physician. MAIN RESULTS: Revisit intervals
      ranged from 1 week to over 1 year. The most common intervals were 12 and 16
      weeks. Physicians' perception of fair-poor health status and visits involving a
      change in management were most strongly related to shorter revisit intervals. In
      multivariate analyses, patient characteristics explained about 18% of the
      variance in revisit intervals, and adding identification of the individual
      provider doubled the explained variance to about 40%. Physician characterization
      of the visit increased explained variance to 57%. The average revisit interval
      adjusted for patient characteristics for each of the 11 physicians varied from 4
      to 20 weeks. Although all physicians lengthened revisit intervals for routine
      visits and shortened them when changing management, the relative ranking of mean
      revisit intervals for each physician changed little for different visit
      characterizations-some physicians were consistently long and others were
      consistently short. CONCLUSION: Physicians vary widely in their recommendations
      for office revisits. Patient factors accounted for only a small part of this
      variation. Although physicians responded to visits in predictable ways, each
      physician appeared to have a unique set point for the length of the revisits
      interval.

PMID- 10203636
TI  - Evidence-based medicine and the practicing clinician.
AB  - OBJECTIVE: To assess the attitudes of practicing general internists toward
      evidence-based medicine (EBM-defined as the process of systematically finding,
      appraising, and using contemporaneous research findings as the basis for clinical
      decisions) and their perceived barriers to its use. DESIGN: Cross-sectional, self
      administered mail questionnaire conducted between June and October 1997. SETTING:
      Canada. PARTICIPANTS: Questionnaires were sent to all 521 physician members of
      the Canadian Society of Internal Medicine with Canadian mailing addresses; 296
      (60%) of 495 eligible physicians responded. Exclusion of two incomplete surveys
      resulted in a final sample size of 294. MAIN RESULTS: Mean age of respondents was
      46 years, 80% were male, and 52% worked in large urban medical centers.
      Participants reported using EBM in their clinical practice always (33, 11%),
      often (173, 59%), sometimes (80, 27%), or rarely/never (8, 3%). There were no
      significant differences in demographics, training, or practice types or locales
      on univariate or multivariate analyses between those who reported using EBM often
      or always and those who did not. Both groups reported high usage of traditional
      (non-EBM) information sources: clinical experience (93%), review articles (73%),
      the opinion of colleagues (61%), and textbooks (45%). Only a minority used EBM
      related information sources such as primary research studies (45%), clinical
      practice guidelines (27%), or Cochrane Collaboration Reviews (5%) on a regular
      basis. Barriers to the use of EBM cited by respondents included lack of relevant
      evidence (26%), newness of the concept (25%), impracticality for use in day-to
      day practice (14%), and negative impact on traditional medical skills and "the
      art of medicine" (11%). Less than half of respondents were confident in basic
      skills of EBM such as conducting a literature search (46%) or evaluating the
      methodology of published studies (34%). However, respondents demonstrated a high
      level of interest in further education about these tasks. CONCLUSIONS: The
      likelihood that physicians will incorporate EBM into their practice cannot be
      predicted by any demographic or practice-related factors. Even those physicians
      who are most enthusiastic about EBM rely more on traditional information sources
      than EBM-related sources. The most important barriers to increased use of EBM by
      practicing clinicians appear to be lack of knowledge and familiarity with the
      basic skills, rather than skepticism about the concept.

PMID- 10203637
TI  - Turfing: patients in the balance.
AB  - OBJECTIVE: To examine the language of "turfing," a ubiquitous term applied to
      some transfers of patients between physicians, in order to reveal aspects of the
      ideology of internal medicine residency. SETTING: Academic internal medicine
      training program. MEASUREMENTS: Using direct observation and a focus group, we
      collected audiotapes of medical residents' discussions of turfing. These data
      were analyzed using interpretive and conversation analytic methods. The focus
      group was used both to validate and to further elaborate a schematic conceptual
      framework for turfing. MAIN RESULTS: The decision to call a patient "turfed"
      depends on the balance of the values of effectiveness of therapy, continuity of
      care, and power. For example, if the receiving physician cannot provide a more
      effective therapy than can the transferring physician, medical residents consider
      the transfer inappropriate, and call the patient a turf. With appropriate
      transfers, these residents see their service as honorable, but with turfs,
      residents talk about the irresponsibility of transferring physicians, burdens of
      service, abuse, and powerlessness. CONCLUSIONS: Internal medicine residents can
      feel angry and frustrated about receiving patients perceived to be rejected by
      other doctors, and powerless to prevent the transfer of those patients for whom
      they may have no effective treatment or continuous relationship. This study has
      implications for further exploration of how the relationships between physicians
      may uphold or conflict with the underlying moral tenets of the medical
      profession.

PMID- 10203638
TI  - Psychiatric disorders in older primary care patients.
AB  - OBJECTIVE: Most older people with psychiatric disorders are never treated by
      mental health specialists, although they visit their primary care physicians
      regularly. There are no published studies describing the broad array of
      psychiatric disorders in such patients using validated diagnostic instruments. We
      therefore characterized Axis I psychiatric diagnoses among older patients seen in
      primary care. DESIGN: Survey of psychopathology using standardized diagnostic
      methods. SETTING: The private practices of three board-certified general
      internists, and a free-standing family medicine clinic. PARTICIPANTS: All
      patients aged 60 years or older who gave informed consent were eligible.
      MEASUREMENTS AND MAIN RESULTS: For the 224 subjects completing the study,
      psychiatric diagnoses were based on the Structured Clinical Interview for DSM-III
      R. Point prevalence estimates used weighted averages based on the stratified
      sampling method. For the combined sites, 31.7% of the patients had at least one
      active psychiatric diagnosis. Prevalent current disorders included major
      depression (6.5%), minor depression (5.2%), dementia (5.0%), alcohol abuse or
      dependence (2. 3%), and psychotic disorders (2.0%). Dysthymic disorder and
      primary anxiety and somatoform disorders were less common and frequently comorbid
      with major depression. CONCLUSIONS: Mental disorders, particularly depression,
      are common among older persons seen in these primary care settings. Clinicians
      should be particularly vigilant about depression when evaluating older patients
      with anxiety or putative somatoform symptoms, given the relatively low
      prevalences of primary anxiety and somatoform disorders.

PMID- 10203639
TI  - Philanthropic endowments in general internal medicine.
AB  - We performed two surveys to uncover the status of philanthropic endowments in
      general internal medicine divisions. The initial survey of U.S. medical school
      departments of medicine found that only 14.1% of general internal medicine
      divisions hold endowments versus 21.9% of all other divisions, and that endowment
      sources for general medicine are atypical. The second survey of successfully
      endowed divisions found that sympathetic administrators and active pursuit of
      endowments were associated with endowment success. Aggressive pursuit of
      endowments, publicizing successes of general medicine, and consideration of
      endowment sources noted in this study are recommended to improve philanthropic
      contributions to general internal medicine.

PMID- 10203640
TI  - Service learning in a homeless clinic.

PMID- 10203641
TI  - Does decision analysis have a race problem?

PMID- 10203643
TI  - Editorial freedom.

PMID- 10203642
TI  - Money and mission? Addressing the barriers to evidence-based medicine.

PMID- 10203644
TI  - Adjusting to the present: presidential address.

PMID- 10203645
TI  - Can more be done in obstetric and gynecologic practice to reduce morbidity and
      mortality associated with venous thromboembolism?

PMID- 10203646
TI  - Increased heterogeneity of chromosome 17 aneuploidy in endometriosis.
AB  - OBJECTIVE: Endometriosis is a complex gynecologic disorder that may display
      features similar to malignancy, including aggressive growth and localized
      invasion of the myometrium or spread to various organs outside the uterus.
      Molecular studies of cancer have demonstrated that genomic instability involving
      chromosome 17 plays a role in the development and progression of various tumor
      types. These involve gain and/or loss, deletions, and mutations of candidate
      tumor suppressor genes (eg, BRCA1 and p53 ) on chromosome 17. STUDY DESIGN: We
      used a 2-color fluorescence in situ hybridization method for analysis of
      endometriotic and normal archival tissue. Centromere-specific and locus-specific
      p53 probes localized to chromosome 17 were selected to study 8 patients with late
      stage (severe) endometriosis. Single cells localized to endometriotic lesions or
      normal endometrial glands were analyzed and identified as normal or abnormal on
      the basis of the distribution of fluorescence in situ hybridization signals.
      RESULTS: Overall, chromosome 17 aneuploidy was significantly greater (P <.05) in
      the endometriosis specimens (mean of 65%) than in normal endometrial cells (mean
      of 25%). No significant difference (P =.1071) in the distribution of fluorescence
      in situ hybridization signals was observed among the 5 normal endometrial
      specimens. However, significant differences (P <. 0001) were observed between the
      8 endometriosis tissue specimens. CONCLUSION: We found increased heterogeneity of
      chromosome 17 aneuploidy in endometriosis. These findings support a multistep
      pathway involving somatic genetic alterations in the development and progression
      of this common disease.

PMID- 10203647
TI  - A randomized comparison of home uterine activity monitoring in the outpatient
      management of women treated for preterm labor.
AB  - OBJECTIVE: The aim of the study was to evaluate home uterine activity monitoring
      as an intervention in reducing the rate of preterm birth among women treated for
      preterm labor. STUDY DESIGN: A total of 186 women were treated in the hospital
      with magnesium sulfate for preterm labor and were prospectively randomly assigned
      to study groups; among these, 162 were ultimately eligible for comparison. Eighty
      two of these women were assigned to the monitored group and 80 were assigned to
      an unmonitored control group. Other than monitoring, all women received identical
      prenatal follow-up, including daily perinatal telephone contact and oral
      terbutaline therapy. Outcome comparisons were primarily directed toward
      evaluation of preterm birth at <35 weeks' gestation. Readmissions for recurrent
      preterm labor and observations lasting <24 hours were evaluated in monitored and
      unmonitored groups. Compliance with monitoring was also evaluated in the
      monitored group. RESULTS: The monitored and control groups were demographically
      similar. According to a multivariate logistic regression model, women with
      cervical dilatation of >/=2 cm were 4 times more likely to be delivered at <35
      weeks' gestation (P <.05). Gestational ages at delivery were similar in the
      monitored and control groups. There was no significant difference in the overall
      rate of preterm delivery at <35 weeks' gestation between the monitored group
      (10.9%) and the control group (15.0%). The overall rates of delivery at <37
      weeks' gestation were high (48.8% and 60.0% for monitored and control groups,
      respectively), and the difference was not significant. The numbers of women with
      >/=1 instance of readmission and treatment for recurrent preterm labor were equal
      in the monitored and control groups. The numbers of women with >/=1 hospital
      observation lasting <24 hours were not different between the groups. Compliance
      with monitoring did not significantly differ for women who were delivered at <35
      weeks' gestation, women with >/=2 cm cervical dilatation at enrollment, or for
      African American women. CONCLUSION: A reduction in the likelihood of preterm
      delivery at <35 weeks' gestation was not further enhanced by the addition of home
      uterine monitoring to the outpatient management regimens of women treated for
      preterm labor.

PMID- 10203648
TI  - Temporal and cell-specific gene expression by human endometrium after coculture
      with trophoblast.
AB  - OBJECTIVE: Our purpose was to identify temporal and stage-specific expression of
      endometrial genes during coculture with trophoblast cells. STUDY DESIGN:
      Endometrial stromal cells were cultured to confluence in the presence of
      estradiol and progesterone. During these culture conditions the gene expression
      of 1 tissue specimen that secreted abundant prolactin (415 ng/mL culture medium
      at 21 days) was compared with a second specimen that did not. These 2 tissues
      were coincubated with trophoblast tissue in a specialized coculture flask. After
      4 and 24 hours of culture messenger ribonucleic acid was extracted and reverse
      transcribed, and the complementary deoxyribonucleic acid products were amplified
      by polymerase chain reactions. The reverse transcriptase-polymerase chain
      reaction products were separated by electrophoresis, and potentially important
      complementary deoxyribonucleic acid fragments were reamplified, inserted into a
      plasmid vector, and sequenced after recovery. Sequences were submitted for Basic
      Local Alignment Search Tool searches of GenBank. RESULTS: We observed up
      regulation of 6 gene fragments in decidualized endometrium after 4 hours of
      coculture with choriocarcinoma-derived trophoblast BeWo cells, but only 1 gene
      fragment was up-regulated after 24 hours of exposure. Conversely, 2 fragments
      were down-regulated in decidualized stroma that was exposed to BeWo for 4 hours
      and 2 fragments were underexpressed after the 24-hour exposure. In the parallel
      experiment stromal cells that failed to secrete prolactin did not elicit the same
      regulation of expression. The nondecidualized endometrium overexpressed 1 gene
      fragment after 4 hours of BeWo exposure and overexpressed 4 gene fragments after
      exposure to BeWo for 24 hours. Underexpression of gene products also occurred
      with the nondecidualized endometrium, and we observed 2 fragments and 1 fragment
      to be underexpressed after 4 and 24 hours of BeWo exposure, respectively. To
      date, 3 of the candidate differential display fragments from these experiments
      have been cloned and sequenced. An up-regulated fragment (C6225J4EB-1) was 99%
      identical (167/168 sequences) to a reported nonredundant expressed sequence tags
      isolated from muscle, brain, ovary, testis, liver, and pregnant uterus tissues. A
      second up-regulated fragment (C4375J4EB-1) matched 100% identity (117/117) with a
      reported gene fragment in the expressed sequence tags database of GenBank that
      was derived from fetal heart and pregnant uterus. Additional characterization of
      these expressed sequence tags has not been reported. The third up-regulated
      fragment (C4250J24EB-2) was 100% identical (265/265) to human reduced
      nicotinamide adenine dinucleotide dehydrogenase III in the nonredundant gene
      database of GenBank. CONCLUSION: This report demonstrates the potential
      usefulness that endometrial-trophoblast coculture and differential display can
      offer for the molecular analysis of implantation phenomena. We have recognized
      both overexpression and underexpression of interesting gene fragments during the
      early phases of endometrial responses to paracrine regulators derived from BeWo
      trophoblast cells. These responses appear to be specific to the degree of
      endometrial transformation (decidualization) before challenge by the trophoblast
      and to the duration of the BeWo exposure. Sequence data identified 1 gene with an
      unidentified function, another gene with a known function, and a fragment not
      previously recognized. We submit that our model of endometrial-trophoblast
      coculture offers a novel tool to test cellular responses during implantation, and
      differential display represents a sensitive technique that can identify many of
      the important elements of genomic signaling during nidation.

PMID- 10203649
TI  - Structural anatomy of the posterior pelvic compartment as it relates to
      rectocele.
AB  - OBJECTIVE: This study was undertaken to define posterior compartment structural
      anatomy relevant to rectocele. STUDY DESIGN: Dissection of 42 fresh and 22 fixed
      cadavers was supplemented by examination of histologic (n = 3) and macroscopic (n
      = 5) serial sections. RESULTS: Distal posterior compartment support involves
      connection of the halves of the perineal membrane (urogenital diaphragm) through
      the perineal body, preventing downward protrusion of the lower rectum. Above this
      level the posterior vaginal wall is held in place by sheets of bilateral
      endopelvic fascia that attach each side of the posterior vaginal wall to the
      pelvic diaphragm. Most of these fascial fibers attach to the vaginal wall and a
      few fibers unite in the midline. Pelvic floor closure by the levator ani muscles
      relieves pressure-induced stress on the midvaginal fascial supports. CONCLUSIONS:
      Midline perineal membrane union supports the distal posterior compartment and a
      fascial connection between the pelvic diaphragm and vagina supports the mid
      vagina. Muscular pelvic floor closure helps to relieve fascial stress.

PMID- 10203650
TI  - Prevalence and incidence of gynecologic disorders among women infected with human
      immunodeficiency virus.
AB  - OBJECTIVE: Our purpose was to ascertain the prevalence, incidence, and predictors
      of gynecologic disorders among women infected with human immunodeficiency virus.
      STUDY DESIGN: We serially assessed 292 women infected with human immunodeficiency
      virus and 681 uninfected women. Outcomes were incidence and prevalence of
      sexually transmitted diseases, viral shedding, findings of Papanicolaou smears,
      fungal infections, and menstrual disorders. RESULTS: Women infected with the
      virus were more likely to have prevalent vulvovaginal candidiasis (odds ratio
      1.80, 95% confidence interval 1. 0-3.25, P =.05), oncogenic human papillomavirus
      (odds ratio 3.79, 95% confidence interval 2.43-5.91, P =.001), abnormal
      Papanicolaou smears (odds ratio 5.40, 95% confidence interval 3.35-8.78, P
      =.001), amenorrhea (4.8% vs 0%, P =.05), positive results on Treponema pallidum
      hemagglutination assay (odds ratio 1.83, 95% confidence interval 1.16-2.88, P
      =.01), infection with cytomegalovirus (odds ratio 4.2, 95% confidence interval
      1.82-10.62, P =.001), and genital warts (odds ratio 6.93, 95% confidence interval
      3.16-16.30, P =.001) but were less likely to have Chlamydia trachomatis infection
      (odds ratio 0.28, 95% confidence interval 0.10-0.66, P =.01). Annual incidence
      rates among women infected with human immunodeficiency virus were 4.0% for
      candidiasis, 22.0% for oncogenic human papillomavirus, 11.4% for genital warts,
      1.7% for infection with C trachomatis, 1.7% for infection with Neisseria
      gonorrhoeae, 10.3% for Trichomonas vaginalis, 1.1% for positive results on T
      pallidum hemagglutination assay, 7.4% for an abnormal Papanicolaou smear, and
      10.9% for infection with herpes simplex virus. Overall, 46.9% had at least 1
      incident condition. Women infected with human immunodeficiency virus were more
      likely to have incident oncogenic human papillomavirus infection (odds ratio 2.0,
      95% confidence interval 1.01-3.8), abnormal Papanicolaou smears (odds ratio 7.76,
      95% confidence interval 2.08-42.8), and genital warts (odds ratio 9. 32, 95%
      confidence interval 3.04-38.0). Incidence and prevalence of sexually transmitted
      diseases and oncogenic human papillomavirus infection increased with increased
      CD4(+) cell counts. CONCLUSIONS: Women infected with the human immunodeficiency
      virus are significantly more likely to have prevalent and incident gynecologic
      disorders but not disorders related to risk taking (eg, incident sexually
      transmitted diseases). The latter disorders increased in women with CD4(+) cell
      counts >500 cells/mm3. Clinicians should be aware of these patterns so that they
      can provide appropriate evaluation and treatment of gynecologic disorders.

PMID- 10203651
TI  - Changes and challenges for women in academic obstetrics and gynecology.
AB  - In obstetrics and gynecology, more than 60% of current residents and 36% of
      medical school faculty are women. However, fewer than 10% of professors and only
      a small number of department chairs and organizational leaders are women. This
      paper reviews the data on the growing number of women in obstetrics and
      gynecology, and in medicine in general, during the past 25 years. It reviews some
      of the challenges that women have faced and some strategies to enhance equitable
      opportunities.

PMID- 10203652
TI  - Ventricular filling patterns of the right and left ventricles in normally grown
      fetuses: a longitudinal follow-up study from early intrauterine life to age 1
      year.
AB  - OBJECTIVE: Our goal was to determine the effects of advancing age on the Doppler
      diastolic filling indexes from early gestation to 1 year of life. STUDY DESIGN:
      Seventy-nine fetuses were studied. Initial Doppler studies were started at about
      the 16th week of gestation and repeated every 4-6 weeks until term, on postnatal
      day 1 and 2, and at ages 6 weeks, 6 months, and 12 months. A minimum of 5
      returning Doppler waveforms were traced and analyzed for (1) peak early flow
      velocity, (2) late peak atrial flow velocity, (3) total area area under the
      curve, and (4) the acceleration and deceleration phases. The stiffness of the
      ventricles was estimated. Slopes of the curves for each of the parameters were
      analyzed for differences across time periods and between right and left
      ventricles. RESULTS: (1) Heart rate significantly decreased with advancing age.
      (2) Left ventricular and right ventricular peak early flow velocity and late peak
      atrial flow velocity significantly increased during fetal life but not during the
      1st year. (3) Atrial predominance was found during fetal life but not during the
      first year. (4) The deceleration phase of filling significantly increased during
      the fetal period. (5) Ventricular stiffness progressively decreased during the
      fetal period. (6) Increased ventricular filling shifted from a right-sided
      dominance in utero to a left-sided dominance after birth. CONCLUSIONS: (1)
      Fetuses have stiffer fetal ventricles than neonates. (2) The diastolic filling
      patterns in normally grown fetuses mimic those of the diseased adult heart. We
      speculate that this maturation process may be affected in fetuses born
      prematurely or small for gestational age.

PMID- 10203653
TI  - Randomized comparison of three surgical methods used at the time of vaginal
      hysterectomy to prevent posterior enterocele.
AB  - OBJECTIVE: This study compared 3 surgical methods of prophylaxis against
      enterocele formation employed at the time of vaginal hysterectomy. STUDY DESIGN:
      One hundred consecutive women undergoing total vaginal hysterectomy for various
      reasons were randomly assigned to have 1 of 3 surgical methods applied to the
      posterior superior aspect of the vagina for prophylaxis against enterocele
      formation. The first procedure involved closing the cul-de-sac and bringing the
      uterosacral-cardinal complex together in the midline in a vaginal Moschcowitz
      type operation. The second procedure was a McCall-type culdeplasty to obliterate
      the cul-de-sac, plicate the uterosacral-cardinal complex, and elevate any
      redundant posterior vaginal apex. The third technique used only the peritoneum to
      close the cul-de-sac, allowing passive movement of the uterosacral-cardinal
      complex to the midline, no obliteration per se, and no elevation of the posterior
      vagina. Postoperative findings on pelvic examination were evaluated at 6 weeks, 3
      months, and 1, 2, and 3 years. Statistical analysis was performed with the chi2
      test of independence. RESULTS: At 6 weeks' follow-up and at 3 months' follow-up
      there were no prolapses involving the posterior superior segment of the vagina.
      At 1 year of follow-up 11 patients had stage 1 or 2 posterior superior segment
      prolapse. At 2 years' follow-up this number was 16. At 3 years' follow-up the
      McCall-type method was statistically better (chi2 = 11.27 with 2 degrees of
      freedom, P =. 004) than the other 2 in preventing postoperative enterocele (n = 2
      of 32 with McCall-type procedure, n = 10 of 33 with vaginal Moschcowitz-type
      procedure, and n = 13 of 33 with peritoneal closure only). CONCLUSION: When
      applied at the time of vaginal hysterectomy the McCall-type culdeplasty is
      superior to a vaginal Moschcowitz-type procedure and to simple peritoneal closure
      in preventing subsequent enterocele.

PMID- 10203654
TI  - In vivo ultrasonographic exposimetry: human tissue-specific attenuation
      coefficients in the gynecologic examination.
AB  - OBJECTIVE: The purpose of the current study was to determine in vivo, tissue
      specific ultrasonic attenuation coefficients for each of the tissue layers
      comprising the anterior abdominal wall, uterus, and vagina with use of a
      quantitative multilayer tissue model. We wanted to validate the "homogeneous"
      tissue model-based Food and Drug Administration derating factor of 0.3 dB/cm-MHz
      applied to obstetric-use ultrasonography systems. STUDY DESIGN: With use of a 3.
      0-MHz mechanical sector scanner and our previously tested exposimetry equipment,
      we obtained a set of at least 5 separate acoustic pressure waveforms from each
      test subject by placing a calibrated 7-element linear-array hydrophone in the
      anterior vaginal fornix while she was undergoing transabdominal ultrasonography.
      Corresponding sets of reference in vitro acoustic pressure waveforms were also
      recorded for each test subject in a 37 degrees C water bath. All linear
      measurements of individual layer thicknesses and total distances were made on
      line with use of electronic calipers. A set of multiple and independent insertion
      loss values, denoted ILn, was calculated for path n between the abdominal surface
      and the hydrophone from n sonograms for each test subject. Each tissue layer type
      was identified and its thickness along each path n was measured. The thickness of
      tissue type m along path n was denoted by dnm. The only unknown quantities left
      were the attenuation coefficients Am of each of the m tissue layers for that test
      subject. The overestimated set of equations dnm Am = ILn was solved for Am with
      use of a nonnegative least-squares solution technique. RESULTS: With use of data
      from 162 independent insertion loss estimate paths, the overall tissue-specific
      attenuation coefficients for each of the tissue layer types, expressed as mean
      value +/- SD, were 2.3 +/- 1.5 dB/cm-MHz for the skin and subcutaneous layer, 3.1
      +/- 2.5 dB/cm-MHz for skeletal muscle, 0.6 +/- 0.5 dB/cm-MHz for myometrium, and
      3.6 +/- 2.7 dB/cm-MHz for the vaginal wall. The overall insertion loss assuming
      the "homogeneous" tissue model was 0.7 +/- 0.3 dB/cm-MHz. CONCLUSIONS: We have
      determined the specific ultrasonic attenuation coefficients for each of the
      tissue layers comprising the anterior abdominal wall, uterus, and vagina and
      validated the Food and Drug Administration derating factor of 0.3 dB/cm-MHz
      applied to obstetric use ultrasonography systems. Of all the models proposed, the
      "homogeneous" tissue model appears to be the best model for determining
      ultrasonic exposure risk during reproductive ultrasonographic examinations.

PMID- 10203655
TI  - Healing persons and therapeutic institutions.

PMID- 10203656
TI  - Atypical glandular cells of undetermined significance in cervical cytologic
      findings.
AB  - OBJECTIVE: Our purpose was to increase our understanding of the clinical
      significance of atypical glandular cells of undetermined origin. STUDY DESIGN:
      All cytologic Papanicolaou smears were reviewed and classified within the context
      of the Bethesda classification system. Charts of all patients with a diagnosis of
      atypical glandular cells of undetermined origin were reviewed for previous
      medical history, diagnostic study, histologic diagnosis, and prior Papanicolaou
      smear abnormalities. RESULTS: The incidence of atypical glandular cells of
      undetermined origin in 76,018 Papanicolaou smears was 0.196%. We reviewed 133
      patient medical records with cytologic diagnoses. Eighty of these patients have
      had appropriate follow-up. Thirty-six (45%) of these were found to have
      significant histologic abnormalities, including 6 patients with cervical
      intraepithelial neoplasia, grades 2 and 3, and 4 invasive cancers. CONCLUSION:
      The frequency of underlying serious histologic changes is much greater in
      atypical glandular cells than in atypical squamous cells of undetermined
      significance. On the basis of our results, we believe that all patients with
      atypical glandular cells should undergo intensive evaluation including
      colposcopy, cervical biopsy, and endocervical curettage. When diagnosis cannot be
      clearly established, patient should undergo endometrial biopsy.

PMID- 10203657
TI  - Time to discard the cookie cutter.

PMID- 10203658
TI  - Hypoxia limits differentiation and up-regulates expression and activity of
      prostaglandin H synthase 2 in cultured trophoblast from term human placenta.
AB  - OBJECTIVE: We determined the effect of hypoxic conditions on cellular
      differentiation and prostaglandin H synthase expression in cultured human term
      trophoblast. STUDY DESIGN: Cytotrophoblasts isolated from term placentas were
      cultured for 24-72 hours in a standard (20% oxygen) or hypoxic (1% to 2% oxygen)
      atmosphere. Trophoblast biochemical differentiation was determined by release of
      human chorionic gonadotropin. Morphologic differentiation was evaluated by
      epifluorescent and confocal microscopic examination of cultures after dual
      cytochemical staining for surface membrane desmosomes and intracytoplasmic
      nuclei. Prostaglandin H synthase 2 expression was determined by Western blot
      analysis and correlated with enzyme activity by immunoassay of 2 prostaglandin H
      synthase 2 products, prostaglandin E2 and thromboxane. RESULTS: Human chorionic
      gonadotropin levels in media and syncytiotrophoblast formation were markedly
      diminished in trophoblast cultured in hypoxia, compared with trophoblast in
      control cultures, whereas viability was unchanged. Hypoxia up-regulated
      expression of trophoblast prostaglandin H synthase 2 but not of prostaglandin H
      synthase 1 and increased prostaglandin E2 and thromboxane release. CONCLUSIONS:
      Hypoxia limits differentiation and enhances prostaglandin H synthase 2 expression
      in cultured villous trophoblast. These responses may account for the
      cytotrophoblast prominence characteristic of placentas exposed to attenuated
      oxygen delivery.

PMID- 10203659
TI  - Longitudinal changes in glucose metabolism during pregnancy in obese women with
      normal glucose tolerance and gestational diabetes mellitus.
AB  - OBJECTIVE: This study prospectively evaluated the longitudinal changes in insulin
      sensitivity, insulin response, and endogenous (primarily hepatic) glucose
      production and suppression during insulin infusion in women with normal glucose
      tolerance (control) and gestational diabetes mellitus before and during a planned
      pregnancy. STUDY DESIGN: Eight control subjects and 7 subjects in whom
      gestational diabetes mellitus developed were evaluated with an oral glucose
      tolerance test, an intravenous glucose tolerance test, and hyperinsulinemic
      euglycemic clamp with infusion of [6,6 (2)H2 ]glucose before conception and at 12
      to 14 and 34 to 36 weeks' gestation. Insulin response was estimated as the area
      under the curve during the intravenous glucose tolerance test. Basal endogenous
      glucose production was estimated from isotope tracer dilution during steady state
      with [6,6 (2)H2 ]glucose and suppression during insulin infusion. Insulin
      sensitivity to glucose was defined as the glucose infusion rate required to
      maintain euglycemia during steady-state insulin infusion. Body composition was
      estimated with hydrodensitometry. Data were analyzed with 2-way analysis of
      variance with repeated measures for 2 groups. RESULTS: There were increases in
      first-phase (P =.006) and second-phase (P =. 0001) insulin responses in both
      groups with advancing gestation, but the increase in second-phase response was
      significantly greater (P =. 02) in the gestational diabetes mellitus group than
      in the control group. Basal glucose production increased significantly (P =.0001)
      with advancing gestation, and there was resistance to suppression during insulin
      infusion in both groups (P =.0001). There was less suppression of endogenous
      glucose production however, in the gestational diabetes mellitus group than in
      the control group (P =. 01). Insulin sensitivity decreased with advancing
      gestation in both groups (P =.0001), and there was lower insulin sensitivity in
      the gestational diabetes mellitus group than in the control group (P =. 04).
      Significant decreases in insulin sensitivity with time (P =. 0001) and between
      groups (P =.03) remained when the data were adjusted for differences in insulin
      concentration or residual hepatic glucose production. CONCLUSION: Obese women in
      whom gestational diabetes mellitus develops have a significant increase in
      insulin response but decreases in insulin sensitivity and suppression of hepatic
      glucose production during insulin infusion with advancing gestation with respect
      to a matched control group. These metabolic abnormalities in glucose metabolism
      are the hallmarks of type 2 diabetes, for which these women are at increased risk
      in later life.

PMID- 10203660
TI  - Peritoneal serous papillary carcinoma, a phenotypic variant of familial ovarian
      cancer: implications for ovarian cancer screening.
AB  - OBJECTIVE: Our purpose was to report the cancers arising during a familial
      ovarian cancer screening program and investigate the tumor's clonality and
      association with BRCA1 and BRCA2 mutations. STUDY DESIGN: Program participants
      with a diagnosis of ovarian cancer or peritoneal serous papillary carcinoma were
      identified and their demographic characteristics, ultrasonographic findings, CA
      125 results, operative reports, and pathology slides reviewed.
      Immunohistochemical analysis of p53, bcl-2, HER-2/neu, and nm23 H1 expression was
      performed on tumor tissues from multiple metastatic sites, and germline BRCA1 and
      BRCA2 mutations were identified. RESULTS: Three stage I ovarian cancers and 7
      cases of peritoneal serous papillary carcinoma were diagnosed from among 1261
      program participants. Ultrasonographic abnormalities triggered surgical
      exploration in all 3 cases of stage I disease. Elevated levels of CA 125 were the
      harbinger in 2 of 7 cases of peritoneal serous papillary carcinoma, abnormal
      ultrasonographic findings prompted diagnosis in 2 of 7 cases, and 3 of 7 women
      had abdominal symptoms 5, 6, and 16 months after screening. Results of
      immunohistochemical studies suggested multifocal disease in 5 of 7 patients with
      peritoneal serous papillary carcinoma. At least 3 of the patients with peritoneal
      serous papillary carcinoma carry BRCA1 185delAG mutations. CONCLUSION: Multifocal
      peritoneal serous papillary carcinoma may be a phenotypic variant of familial
      ovarian cancer, and screening strategies for these women cannot rely on
      ultrasonography and CA 125 testing to detect early disease.

PMID- 10203661
TI  - Condom practices of urban teens using Norplant contraceptive implants, oral
      contraceptives, and condoms for contraception.
AB  - OBJECTIVES: The availability of long-acting hormonal birth control methods has
      created new contraceptive options for adolescents. The purpose of this study was
      to determine whether teens initiating these methods use condoms less frequently
      than teens using oral contraceptive pills or condoms alone and may therefore be
      at an increased risk of acquiring sexually transmitted infections. STUDY DESIGN:
      To investigate ongoing condom behavior in teens using levonorgestrel (Norplant)
      contraceptive implants, oral contraceptives, and condoms alone, we examined data
      from a 2-year prospective cohort study of 399 urban teens. The study consisted of
      3 clinic-based cohorts of adolescent female contraceptive users: Norplant
      contraceptive implants (n = 200), oral contraceptives (n = 100), and condoms
      alone (n = 99). Data were collected at an admission interview and at 1- and 2
      year follow-up from method continuers. RESULTS: Norplant contraceptive implant
      users were less likely than oral contraceptive or condom users to report condom
      use at last sex or consistent condom use at 1- and 2-year follow-up. The implant
      group showed a significant decrease in condom use from admission to 2 years after
      method initiation. The proportion of implant users self-reporting new sexually
      transmitted infections at 2-year follow-up, however, was not significantly
      greater than that of oral contraceptive or condom users. CONCLUSIONS: Our
      findings indicate that teen users of Norplant contraceptive implants are less
      likely to use condoms than teens who choose oral contraceptives but, probably
      because of differences in sexual behavior, are no more likely to self-report
      sexually transmitted infections. Our findings also indicate that teens who choose
      oral contraceptives and condoms do not use them consistently enough to avoid
      pregnancies or sexually transmitted infections.

PMID- 10203662
TI  - Ruptured tubal ectopic pregnancy: risk factors and reproductive outcome: results
      of a population-based study in France.
AB  - OBJECTIVE: The aim of this study was to investigate the determinants of tubal
      rupture and to describe its treatment and effect on subsequent fertility. STUDY
      DESIGN: The data were taken from a population-based register from Auvergne
      (France). All women aged between 15 and 45 years residing permanently in this
      area and treated for ectopic pregnancy by surgical or medical procedures have
      been registered since 1992. They are then followed up prospectively until the age
      of 45 years. This study is an analysis of 849 tubal ectopic pregnancies
      registered between January 1992 and December 1996. Women with tubal rupture were
      compared with those in whom no tubal rupture occurred. The risk factors for tubal
      rupture were identified by calculating crude and adjusted odds ratios. The
      effects of tubal rupture on subsequent fertility were assessed by calculating
      cumulative intrauterine pregnancy rates and were analyzed by log-rank tests and
      Cox regression. RESULTS: The rate of rupture for this population was 18%. Four
      factors were identified that increased the risk of rupture (results of the
      multivariate analysis): never having used contraception (odds ratio 1.7 [1.0 to
      3. 3]), a history of tubal damage together with infertility (odds ratio 1.6 [0.9
      to 2.7]), induction of ovulation (odds ratio 2.5 [1.1 to 5. 6]), and a high level
      of beta-human chorionic gonadotropin (at least 10,000 IU/L) when ectopic
      pregnancy was suspected (odds ratio 2.9 [1. 5 to 5.6]). The overall cumulative
      frequency of intrauterine pregnancy was not significantly lower after tubal
      rupture (adjusted risk ratio 0.85 [0.53 to 1.38]). CONCLUSION: Although tubal
      rupture seriously affects the immediate health of the women concerned, it seems
      to have no independent effect on subsequent fertility. Better knowledge of the
      risk factors should make it possible to identify those women who will not benefit
      from nonsurgical treatment.

PMID- 10203663
TI  - Predictors of hysterectomy: an Australian study.
AB  - OBJECTIVE: We evaluated the relative importance of predictors of hysterectomy.
      STUDY DESIGN: A questionnaire survey of an Australia-wide sample of adult female
      twins was conducted; self-report data were validated against reports from
      treating physicians. RESULTS: A total of 3096 women (94%) and 366 physicians
      (87%) responded. The sensitivity of patient report of hysterectomy was 98.2%.
      Best predictors of hysterectomy were endometriosis (odds ratio 4.85, 95%
      confidence interval 3.17-7.43), medical consultation for menorrhagia (odds ratio
      3.55, 95% confidence interval 2.47-5.12), joint effects of fibroids with medical
      consultation for chronic or persisting pelvic pain (odds ratio 3.34, 95%
      confidence interval 1. 42 to 7.87), having smoked >40 cigarettes per day (odds
      ratio 3.24, 95% confidence interval 1.10-9.55), joint effects of fibroids with
      consultation for menstrual problems (odds ratio 2.61, 95% confidence interval
      1.36-5.01), and tubal ligation (odds ratio 1.77, 95% confidence interval 1.31
      2.39). Less-important predictors were age and higher education level
      (protective). CONCLUSION: Consulting a physician about pelvic pain and menstrual
      problems, especially heavy bleeding, are recognized steps toward hysterectomy. Of
      particular interest for future genetic analyses are the high odds of hysterectomy
      for women with endometriosis, fibroids, or menorrhagia.

PMID- 10203664
TI  - Prospective randomized clinical trial of laparoscopically assisted vaginal
      hysterectomy versus total abdominal hysterectomy.
AB  - OBJECTIVE: We compared operative time, length of hospital stay, postoperative
      recovery, return to work, and costs for women undergoing laparoscopically
      assisted vaginal hysterectomy or abdominal hysterectomy. STUDY DESIGN: A
      prospective randomized clinical trial of laparoscopically assisted vaginal
      hysterectomy (n = 24) versus abdominal hysterectomy (n = 24) was carried out in a
      tertiary care setting. The main outcome variables were operative time, length of
      hospital stay, and return to work. Secondary outcomes were postoperative pain and
      return to normal activity as determined by weekly visual analog scales and daily
      diary. Hospital costs were calculated. RESULTS: The laparoscopically assisted
      vaginal hysterectomy group had longer operative times (median and quartiles,
      laparoscopically assisted vaginal hysterectomy 180 [139, 225] minutes vs
      abdominal hysterectomy 130 [97, 155] minutes), lower requirements for
      postoperative intravenous analgesia (patient-controlled analgesia pump, median
      and quartiles: laparoscopically assisted vaginal hysterectomy 22.1 [15.9, 23.5]
      hours, abdominal hysterectomy 36.7 [26.2, 45.0] hours), shorter length of
      hospital stay (median and quartiles, laparoscopically assisted vaginal
      hysterectomy 1.5 [1.0, 2.3] days, abdominal hysterectomy 2.5 [1.5, 2.5] days),
      and quicker return to work (Kaplan-Meier analysis, P =.03). Both procedures had
      similar hospital costs (P =.21). CONCLUSION: Laparoscopically assisted vaginal
      hysterectomy appears to allow patients a more rapid postoperative recovery and an
      earlier return to work with hospital costs similar to those of abdominal
      hysterectomy.

PMID- 10203666
TI  - Epidural analgesia in association with duration of labor and mode of delivery: a
      quantitative review.
AB  - OBJECTIVE: This study was undertaken to quantitatively summarize previous
      literature on the effects of epidural analgesia in labor on the duration of labor
      and mode of delivery. STUDY DESIGN: Original studies published in English from
      1965 through December 1997 were reviewed and assigned a quality score
      independently by 2 of the authors. Studies that met the minimal requirements were
      evaluated further. Data syntheses were performed separately according to study
      design and outcome measurements, including cesarean delivery, instrumental
      delivery, oxytocin augmentation, and durations of the first and second stages of
      labor. RESULTS: Seven randomized clinical trials and 5 observational studies met
      the minimal requirements. Among them 4 studies of each sort were included in the
      data synthesis. Both types of studies showed that epidural analgesia increased
      risk of oxytocin augmentation 2-fold. Clinical trials suggested that epidural
      analgesia did not increase the risk of cesarean delivery either overall or for
      dystocia, nor did it significantly increase the risk of instrumental vaginal
      delivery; however, observational studies reported a more than 4-fold increased
      risk of cesarean and instrumental deliveries. Although most studies showed a
      longer labor among women with epidural analgesia than without it, especially
      during the second stage, most of the studies used inappropriate statistical
      analysis. CONCLUSION: Epidural analgesia with low-dose bupivacaine may increase
      the risk of oxytocin augmentation but not that of cesarean delivery.

PMID- 10203665
TI  - Ovarian preservation in the surgical treatment of cervical carcinoma.
AB  - OBJECTIVES: In the surgical treatment of cervical carcinoma the conservation of
      ovaries in premenopausal women is a common procedure. To date, however, there
      have been no controlled studies to prove that the risk of recurrence or death
      from disease is not elevated among women who do not undergo oophorectomy. STUDY
      DESIGN: We performed a matched pairs analysis according to the tumor volume,
      comparing the outcomes of patients with in situ conservation of >/=1 ovary with
      those of control subjects who underwent bilateral oophorectomy. From among 658
      patients, 150 pairs with International Federation of Gynecology and Obstetrics
      stage I disease were matched. Kaplan-Meier survival curves were compared with the
      log rank test. RESULTS: Among patients who retained their ovaries 5- and 10-year
      overall survival rates were 98% and 96%, respectively, versus 97% and 97% for the
      oophorectomy control group. The corresponding figures for progression-free
      survival were 95% and 94%, respectively, versus 97% and 93%. Outcomes were equal
      with sufficient power to detect a 10% difference. Three of 214 patients with
      conservation of ovaries (1.3%) subsequently required oophorectomy, all because of
      benign ovarian diseases. CONCLUSIONS: Our results confirm that ovarian
      conservation is safe in International Federation of Gynecology and Obstetrics
      stage I disease and that the occurrence of subsequent complications in ovaries
      retained in situ is rare.

PMID- 10203667
TI  - Changes in 24-hour heart rate variability during normal pregnancy.
AB  - OBJECTIVE: We studied the effects of normal pregnancy on heart rate variability
      as a noninvasive index of maternal cardiovascular autonomic modulation. STUDY
      DESIGN: Twenty-four-hour Holter recordings were obtained for 8 healthy pregnant
      volunteers during early pregnancy (</=6 weeks after conception); at 10, 18, and
      34 weeks after conception; and while the subjects were not pregnant. Another 12
      subjects underwent 2 to 4 recordings in the sequence. Heart rate variability and
      nighttime respiratory rates were determined. RESULTS: Maternal heart rate
      variability declined during pregnancy. Virtually all indexes were significantly
      decreased with respect to the nonpregnant state in early pregnancy, and
      respiratory rate was increased. Changes in heart rate, heart rate variability,
      and respiratory rates between subsequent stages were modest. Individual changes
      in heart rate, heart rate variability, and respiration during pregnancy varied in
      both magnitude and direction. CONCLUSION: Most of the change in cardiac autonomic
      modulation and respiration during pregnancy occurs within the first 6 weeks after
      conception. There is considerable variability in individual heart rate and heart
      rate variability changes during a normal pregnancy.

PMID- 10203668
TI  - Undiagnosed maternal phenylketonuria: the need for prenatal selective screening
      or case finding.
AB  - OBJECTIVES: The aims of this article are to report on a review of cases of
      maternal phenylketonuria in the International Maternal Phenylketonuria
      Collaborative Study that were initially diagnosed during or after a pregnancy, to
      alert health care practitioners to the possible existence of women with
      undiagnosed phenylketonuria whose fetuses are at risk, and to emphasize that not
      all adults with untreated phenylketonuria are mentally retarded. STUDY DESIGN:
      The study was conducted through retrospective database review. RESULTS: Of 414
      women with live-born infants, 17 fulfilled our criteria. Six had phenylketonuria
      diagnosed after they had produced >/=1 affected offspring, 2 had phenylketonuria
      diagnosed as a result of transient postnatal hyperphenylalaninemia in an
      offspring, and 9 had phenylketonuria diagnosed by prenatal screening. Undiagnosed
      maternal phenylketonuria in North America and Europe is currently estimated at 1
      case/100,000 births; this rate could be higher elsewhere. CONCLUSIONS: Physicians
      and midwives should consider a protocol of selective prenatal screening or case
      finding to detect undiagnosed phenylketonuria among their patients.

PMID- 10203669
TI  - Repeated use of betamethasone in rabbits: effects of treatment variation on
      adrenal suppression, pulmonary maturation, and pregnancy outcome.
AB  - OBJECTIVE: The aim of the study was to determine whether reduced birth weight,
      adrenal suppression, and lung maturation occur in parallel and are cumulative
      with increasing courses of betamethasone. STUDY DESIGN: Time-bred rabbits were
      assigned to a control group or to receive saline solution or 1, 2, or 3 courses
      of betamethasone (early treatment, beginning day 19). Two additional groups (n =
      5 per group) were given 1 or 2 late courses (late treatment). Birth weight, serum
      cortisol, adrenal 17alpha-hydroxylase (P450c17) messenger ribonucleic acid and
      fetal lung surfactant proteins A and B were quantified on day 27. RESULTS: Fetal
      weight was inversely proportional to the number of courses, with late treatment
      having a greater effect. Maternal cortisol and P450c17 levels were progressively
      suppressed with each early course, but fetal cortisol and P450c17 levels were
      only suppressed after 3 courses. A single late treatment profoundly suppressed
      both maternal and fetal cortisol and P450c17 messenger ribonucleic acid levels.
      In contrast, fetal lung surfactant proteins A and B increased progressively with
      betamethasone courses, regardless of timing. CONCLUSIONS: Time from last
      injection to delivery determined adrenal suppression, whereas total betamethasone
      courses determined surfactant protein production. Lower birth weight was
      dependent on the number of courses and was greater with late treatment.

PMID- 10203670
TI  - Prenatal diagnosis of 46,XX male fetuses.
AB  - Ultrasonography can accurately determine phenotypic sex differences from those of
      the genetic sex. Two cases were identified; they were the result of a
      translocation of the SRY gene from the Y chromosome to the X chromosome during
      meiosis. An ultrasonographic difference may represent an otherwise unsuspected
      genetic abnormality.

PMID- 10203671
TI  - Annexin V is critical in the maintenance of murine placental integrity.
AB  - OBJECTIVES: Recurrent fetal loss can be a consequence of placental thrombosis,
      frequently occurring in autoimmune disorders such as antiphospholipid syndrome. A
      potent anticoagulant, annexin V, is abundant in placental tissues. We
      investigated the role of annexin V in maintaining fetal viability. STUDY DESIGN:
      Sites of annexin V activity in placenta were found and neutralized, and the
      physiologic consequences on fetal development were evaluated. To find
      extracellular binding sites for annexin V on placental membrane, 2 approaches
      were taken. An epitope-tagged recombinant annexin V was infused into pregnant
      BALB/c mice. Endogenous annexin V was evaluated by immunohistochemical
      techniques. To define a role for annexin V during pregnancy, annexin V was
      neutralized by tail-vein infusion of affinity-purified anti-annexin V antibodies
      immediately before mating, 16 hours before the vaginal plugs were observed. Fetal
      viability, number, and size were evaluated at days 11 or 15 after conception.
      RESULTS: Endogenous annexin V is enriched along the apical surfaces of
      trophoblasts. Animals infused with epitope-tagged annexin V had confirmed
      presence of extracellular binding sites for annexin V exclusively along these
      surfaces. In mice infused with anti-annexin V antibodies, various degrees of
      fetal absorption were observed. Thrombosis and necrosis were present in the fetal
      component of placentas from partially absorbed embryos. Focal necrosis and
      fibrosis were present in the decidua of placentas from embryos that were
      significantly smaller than the normal embryos in the same uterus. CONCLUSIONS:
      Apical surfaces of syncytiotrophoblasts in the placenta possess annexin V binding
      sites. The binding of annexin V to these coagulation-promoting surfaces is
      crucial for the maintenance of blood flow through the placenta and consequently
      for fetal viability. Infusion of anti-annexin V antibodies decreased the
      availability of annexin V to bind to the trophoblast surfaces and caused
      placental thrombosis, necrosis, and fetal loss. Our study suggests that anti
      annexin V autoantibodies may contribute to recurrent pregnancy failure resulting
      from placental thrombosis, as found in patients with certain autoimmune diseases.

PMID- 10203672
TI  - Placental expression of glucose transporter proteins 1 and 3 in growth-restricted
      fetal rats.
AB  - OBJECTIVE: The purpose of this study was to determine the effect of intrauterine
      growth restriction on the placental expression of glucose transporter proteins.
      STUDY DESIGN: Intrauterine growth restriction was induced by bilateral uterine
      artery ligation in the pregnant rat at a gestational age of 19 days (term is 21.5
      days). Maternal rats were killed and fetuses were delivered by hysterotomy on
      gestational days 20 and 21. Control fetuses from mothers that had been subjected
      to a sham operation were studied simultaneously. Glucose transporter protein 1
      and glucose transporter protein 3 messenger ribonucleic acid was quantified by
      reverse transcriptase-polymerase chain reaction amplification. Glucose
      transporter protein 1 and glucose transporter protein 3 densities in placental
      membranes were also assessed by Western blotting and by immunohistochemical
      analysis. RESULTS: Glucose transporter protein 1 messenger ribonucleic acid,
      expressed as a multiple of the matched sham control value, was unchanged on both
      days 20 and 21 of gestation. Glucose transporter protein 3 messenger ribonucleic
      acid was also unchanged. Western blotting demonstrated no change in expression of
      glucose transporter protein 1 or glucose transporter protein 3 on either day 20
      or 21 of gestation. Immunohistochemical staining patterns for glucose transporter
      protein 1 and glucose transporter protein 3 on the syncytiotrophoblastic
      membranes were similar between the growth-restricted group and the sham control
      group. CONCLUSION: Placental expression of glucose transporter proteins in the
      pregnant rat is unchanged with uteroplacental insufficiency.

PMID- 10203673
TI  - Newborn assessment and long-term adverse outcome: a systematic review.
AB  - The medical literature was searched for publications between 1966 and September
      1997 for data on the association of Apgar score, umbilical blood pH, or Sarnat
      grading of encephalopathy with long-term adverse outcome. Odds ratios for these
      associations were combined to calculate common odds ratios with 95% confidence
      intervals. Our search identified abstracts of 1312 studies and 81 articles with
      sufficient numeric data to formulate contingency tables. Forty-two of these
      qualified for inclusion in our meta-analysis. The strongest associations in the
      prediction of neonatal death were found by comparing umbilical artery pH <7 with
      pH >/=7 (common odds ratio 43; 95% confidence interval 15-124) and by comparing
      Sarnat grade III with grade II (common odds ratio 24; 95% confidence interval 13
      45). In the prediction of cerebral palsy, the strongest associations were found
      for Sarnat grade III versus grade II (common odds ratio 20; 95% confidence
      interval 6-70) and for 20-minute Apgar score 0 to 3 versus 4 to 6 (common odds
      ratio 15; 95% confidence interval 5-50).

PMID- 10203674
TI  - Traumatic liver rupture in pregnancy.
AB  - Two pregnant women, 1 in the second trimester and 1 in the third trimester,
      sustained blunt liver trauma as unrestrained drivers in motor vehicle accidents.
      One patient had an overt injury that was apparent on computerized tomography and
      underwent surgical exploration when nonreassuring fetal monitoring occurred. The
      second patient, discharged after 23 hours of normal observation, returned a day
      later with overt intra-abdominal hemorrhage from an obvious liver laceration.

PMID- 10203675
TI  - Fetal meconium peritonitis after maternal hepatitis A.
AB  - Hepatitis A virus has rarely been implicated in congenital infections. After
      maternal hepatitis A at 13 weeks' gestation, ultrasonographic examinations
      revealed fetal ascites (20 weeks) and meconium peritonitis (33 weeks). After
      delivery, a perforated distal ileum was resected. Elevated levels of hepatitis A
      immunoglobulin G persisted in the infant 6 months after delivery.

PMID- 10203676
TI  - Biochemical alterations of uterine leiomyoma extracellular matrix in type IV
      Ehlers-Danlos syndrome.
AB  - Collagens and glycosaminoglycans were assessed in 6 leiomyomas from otherwise
      healthy ("control") patients and 1 leiomyoma from a patient with type IV Ehlers
      Danlos syndrome. The type IV Ehlers-Danlos leiomyoma contained less type III
      collagen and dermatan sulfate than control leiomyomas. This might contribute to
      the formation of a defective collagen network in type IV Ehlers-Danlos syndrome.

PMID- 10203677
TI  - Complications caused by extramembranous placement of intrauterine pressure
      catheters.
AB  - A case report is described in which the inadvertent placement of a standard
      intrauterine pressure catheter in a laboring woman caused partial abruptio
      placentae and disseminated intravascular coagulation. Altering catheter placement
      technique and giving attention to aspects of placement can help avoid mishaps,
      and awareness of possible complications can lead to earlier diagnosis with
      increased appropriate intervention.

PMID- 10203678
TI  - Desmoid tumor of the larynx complicating pregnancy: a case report.
AB  - Desmoid tumors are locally invasive fibrous neoplasms that arise from
      musculoaponeurotic structures. We report the first case of a desmoid tumor of the
      larynx complicating pregnancy. At 21 weeks' gestation fiberoptic and indirect
      otolaryngologic examination of the patient's larynx revealed a submucosal tumor
      involving the left true vocal cord, ventricle of the larynx, and false vocal
      cord. Histopathologic examination revealed areas of extensive fibrosis intermixed
      with degenerated vocal cord skeletal muscle. Despite a subtotal excisional
      biopsy, growth of the desmoid tumor continued during pregnancy. Endoscopic
      evaluation 9 weeks post partum revealed complete regression of the tumor.

PMID- 10203679
TI  - Management of splenic artery aneurysm rupture during trial of scar with epidural
      analgesia.
AB  - We report a case of ruptured splenic artery aneurysm during labor in which the
      clinical signs were masked by epidural analgesia. A high index of clinical
      suspicion must be maintained in cases of atypical epidural breakthrough pain, and
      attending clinicians must be prepared for the unexpected when faced with a
      maternal collapse.

PMID- 10203680
TI  - Creatine kinase as a biochemical marker in diagnosis of placenta increta and
      percreta.
AB  - We describe 1 case of placenta increta and 1 of placenta percreta, both
      associated with elevated maternal serum creatine kinase concentration. In
      patients with placenta previa and ultrasonographic findings of an abnormally
      adherent placenta, an unexplained elevation in maternal serum creatine kinase
      level should alert the clinician to the possibility of placenta increta or
      placenta percreta, with an attendant increase in maternal morbidity.

PMID- 10203681
TI  - Vulvar paraneoplastic amyloidosis with the appearance of a vulvar carcinoma.
AB  - Nodular cutaneous amyloidosis of the vulva is a rare phenomenon. We describe a
      patient with localized nodular lesions on the vulva that mimicked kissing ulcers
      such as are seen with vulvar carcinoma. These lesions were a result of multiple
      myeloma with subsequent primary systemic amyloidosis. The patient died of cardiac
      and renal decompensation 2 months after diagnosis.

PMID- 10203682
TI  - Ongoing pregnancy after intracytoplasmic injection of testicular spermatozoa into
      cryopreserved human oocytes.
AB  - Human oocyte cryopreservation has met with limited success in terms of both
      survival and subsequent fertilization. We recently reported the first birth of a
      healthy female infant after intracytoplasmic sperm injection of cryopreserved
      oocytes. The current report describes the first pregnancy achieved after
      intracytoplasmic injection of testicular sperm into cryopreserved human oocytes.

PMID- 10203683
TI  - Inhaled nitric oxide therapy in pregnancy complicated by pulmonary hypertension.
AB  - The use of nitric oxide as an agent to reduce pulmonary artery pressure in a
      pregnancy complicated by pulmonary hypertension is reported for the first time.
      This therapy can reduce pulmonary vascular resistance and therefore potentially
      enable the right ventricle to better compensate for the physiologic changes of
      pregnancy.

PMID- 10203684
TI  - Shoulder dystocia risks.

PMID- 10203686
TI  - Suramin induced ceramide accumulation leads to apoptotic cell death in dorsal
      root ganglion neurons.
AB  - Suramin is an experimental antineoplastic agent that is currently being tested in
      clinical trials for a number of human cancers. In previous clinical trials, it
      has been noted that a significant percentage of patients treated with suramin
      develop a peripheral neuropathy. Both the cytotoxic (chemotherapeutic) and
      neurotoxic mechanisms of action of this compound are unknown. Evidence presented
      in this study suggests that both effects may be due to extensive disruption in
      glycolipid transport and/or metabolism. Suramin treated dorsal root ganglion
      cultures revealed an accumulation of the GM1 ganglioside and ceramide. Exposure
      of cultures to suramin, a cell permeable ceramide analog, or sphingomyelinase
      lead to apoptotic cell death demonstrated by electron microscopy, bis-benzimide
      staining and DNA laddering on gel electrophoresis. Furthermore, a significant
      increase in intracellular ceramide preceded cell death in suramin treated
      neurons. We propose that suramin induced ceramide accumulation within neurons
      leads to apoptotic cell death.

PMID- 10203685
TI  - Hypersensitivity to seizures in beta-amyloid precursor protein deficient mice.
AB  - Secreted forms of the beta-amyloid precursor protein (beta-APP) have
      neuroprotective properties in vitro and may be involved in the containment of
      neuronal excitation. To test whether loss of secreted forms of beta-APP (sAPPs)
      may enhance excitotoxic responses, we injected mice homozygous for a targeted
      mutation of the beta-APP gene (beta-APPDelta/Delta) intraperitoneally with kainic
      acid. We found that in these mice, kainic acid induced seizures initiated
      earlier, and acute mortality was enhanced compared to isogenic wild-type mice
      independently from the callosal agenesis phenotype observed to occur at increased
      frequency in APP mutant mice. Expression of c-fos in cortex and cingulate gyrus
      was enhanced in beta-APPDelta/Delta mice, although the amount of structural
      damage and apoptosis in the hippocampal pyramidal cell layer and cortex was
      similar to that of controls. When cerebellar granule cell cultures and cortical
      neuronal cultures were challenged with glutamate receptor agonists, the rates of
      cell death and apoptosis of beta-APPDelta/Delta mice were indistinguishable from
      those of controls. Therefore, deficiency of sAPPs causes facilitation of seizure
      activity in the absence of enhanced cell death. Since enhanced seizures were
      observed also in mice homozygous for a deletion of the entire beta-APP gene, this
      phenotype results from a loss of APP rather than from a dominant effect of
      APPDelta.

PMID- 10203687
TI  - Activation of the CD95 (APO-1/Fas) pathway in drug- and gamma-irradiation-induced
      apoptosis of brain tumor cells.
AB  - Chemotherapeutic agents and gamma-irradiation used in the treatment of brain
      tumors, the most common solid tumors of childhood, have been shown to act
      primarily by inducing apoptosis. Here, we report that activation of the CD95
      pathway was involved in drug- and gamma-irradiation-induced apoptosis of
      medulloblastoma and glioblastoma cells. Upon treatment CD95 ligand (CD95-L) was
      induced that stimulated the CD95 pathway by crosslinking CD95 via an
      autocrine/paracrine loop. Blocking CD95-L/receptor interaction using F(ab')2 anti
      CD95 antibody fragments strongly reduced apoptosis. Apoptosis depended on
      activation of caspases (interleukin 1beta-converting enzyme/Ced-3 like proteases)
      as it was almost completely abrograted by the broad range caspase inhibitor
      benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone. Apoptosis was mediated by
      cleavage of the receptor proximal caspase FLICE/MACH (caspase-8) and the
      downstream caspase CPP32 (caspase-3, Apopain) resulting in cleavage of the
      prototype caspase substrate PARP. Moreover, CD95 was upregulated in wild-type p53
      cells thereby increasing responsiveness towards CD95 triggering. Since activation
      of the CD95 system upon treatment was also found in primary medulloblastoma cells
      ex vivo, these findings may have implications to define chemosensitivity and to
      develop novel therapeutic strategies in the management of malignant brain tumors.

PMID- 10203688
TI  - Extended therapeutic window for caspase inhibition and synergy with MK-801 in the
      treatment of cerebral histotoxic hypoxia.
AB  - In rats, striatal histotoxic hypoxic lesions produced by the mitochondrial toxin
      malonate resemble those of focal cerebral ischemia. Intrastriatal injections of
      malonate induced cleavage of caspase-2 beginning at 6 h, and caspase-3-like
      activity as identified by DEVD biotin affinity-labeling within 12 h. DEVD
      affinity-labeling was prevented and lesion volume reduced in transgenic mice
      overexpressing BCL-2 in neuronal cells. Intrastriatal injection of the
      tripeptide, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD-fmk), a
      caspase inhibitor, at 3 h, 6 h, or 9 h after malonate injections reduced the
      lesion volume produced by malonate. A combination of pretreatment with the NMDA
      antagonist, dizocilpine (MK-801), and delayed treatment with zVAD-fmk provided
      synergistic protection compared with either treatment alone and extended the
      therapeutic window for caspase inhibition to 12 h. Treatment with cycloheximide
      and zVAD-fmk, but not with MK-801, blocked the malonate-induced cleavage of
      caspase-2. NMDA injections alone resulted in a weak caspase-2 cleavage. These
      results suggest that malonate toxicity induces neuronal death by more than one
      pathway. They strongly implicate early excitotoxicity and delayed caspase
      activation in neuronal loss after focal ischemic lesions and offer a new strategy
      for the treatment of stroke.

PMID- 10203689
TI  - Trophic support promotes survival of bcl-x-deficient telencephalic cells in
      vitro.
AB  - Survival of immature neurons is regulated by Bcl-xL, as targeted disruption of
      bcl-x significantly increases cell death in vivo and in vitro. Death of cultured
      bcl-x-deficient and wild-type telencephalic cells can be prevented by fetal calf
      serum or chemically-defined medium (ITS), suggesting trophic factors in these
      media potentiate survival through a pathway independent of Bcl-xL. Addition of
      trophic factors to basal medium revealed that insulin and insulin-like growth
      factors (IGFs), but not other trophic factors, reduced apoptosis of wild-type and
      bcl-x-deficient telencephalic cells. Antibodies raised against IGF-I receptors
      and wortmannin both attenuated the effects of IGF-I, indicating survival was
      mediated by IGF-I receptors and phosphatidylinositol 3'-kinase signaling, whereas
      effects of ITS were only partially reduced by these agents. The survival
      promoting effects of ITS were reduced in cells lacking both bcl-x and bcl-2,
      indicating Bcl-2 plays a supportive role to Bcl-xL in maintaining telencephalic
      cell survival. Furthermore, the ratio of expression of the pro-apoptotic bax gene
      to the anti-apoptotic bcl-2 gene was reduced in bcl-x-deficient cultures grown in
      ITS, suggesting that the interaction between these bcl-2 family members may, in
      part, regulate a Bcl-xL independent survival pathway. Finally, the pro-apoptotic
      bad gene does not appear to play a role in these interactions as targeted
      disruption of bad did not alter apoptosis in telencephalic cultures.

PMID- 10203690
TI  - How to fight brain cell suicide, and feel good at it.

PMID- 10203691
TI  - Why do mature CNS neurons of mammals fail to re-establish connections following
      injury--functions of bcl-2.
AB  - Factors inside and outside neurons control the process of axonal growth and
      regeneration. Recently, it has become apparent that neurons are determined
      intrinsically for their ability to grow axons. In the mammalian CNS, the
      intrinsic machinery of neurons that triggers the growth of axons during early
      embryonic stages is shut down at a certain point in development; as a
      consequence, axon elongation and regeneration cannot occur in postnatal life. The
      proto-oncogene Bcl-2 has been recognized to act as a key regulator for the
      program of axon elongation inside neurons. However, expressing the gene Bcl-2 in
      CNS neurons is not sufficient to induce nerve regeneration in the adult CNS,
      eliminating the inhibitory mechanism in the mature CNS environment is still
      required. Recently, the formation of glia scar has been reported to be the major
      limiting factor in the CNS environment that blocks nerve regeneration. These new
      discoveries challenge the classical view of nerve regeneration in the mammalian
      CNS. It opens up a new dimension in the study of the cellular and molecular
      mechanisms underlying neurodevelopmental and neurodegenerative diseases.

PMID- 10203692
TI  - Fatal attractions: abnormal protein aggregation and neuron death in Parkinson's
      disease and Lewy body dementia.
AB  - The abnormal aggregation of proteins into fibrillar lesions is a
      neuropathological hallmark of several sporadic and hereditary neurodegenerative
      diseases. For example, Lewy bodies (LBs) are intracytoplasmic filamentous
      inclusions that accumulate primarily in subcortical neurons of patients with
      Parkinson's disease (PD), or predominantly in neocortical neurons in a subtype of
      Alzheimer's disease (AD) known as the LB variant of AD (LBVAD) and in dementia
      with LBs (DLB). Aggregated neurofilament subunits and alpha-synuclein are major
      protein components of LBs, and these inclusions may contribute mechanistically to
      the degeneration of neurons in PD, DLB and LBVAD. Here we review recent studies
      of the protein building blocks of LBs, as well as the role LBs play in the onset
      and progression of PD, DLB and LBVAD. Increased understanding of the protein
      composition and pathological significance of LBs may provide insight into
      mechanisms of neuron dysfunction and death in other neurodegenerative disorders
      characterized by brain lesions containing massive deposits of proteinacious
      fibrils.

PMID- 10203693
TI  - ICE, neuronal apoptosis and neurodegeneration.
AB  - Significant progress has recently occurred in the understanding of the molecular
      mechanisms mediating vertebrate programmed cell death, or apoptosis. New advances
      in this field have stemmed from the identification of ICE (caspase-1) as the
      founding member of the mammalian caspase cell death family. Apoptotic cell death
      plays an important role in neuronal cell death. Both in vitro and in vivo
      evidence implicates ICE as an important factor in neuronal apoptosis, especially
      under pathological conditions. In addition, other caspases, such as caspase-3,
      have also been shown to be activated and may play a role in pathological neuronal
      loss. Understanding the basic mechanisms mediating cell death in
      neurodegenerative disease may lead to the development of novel approaches for the
      treatment of diseases featuring apoptosis.

PMID- 10203694
TI  - Platelet activating factor receptor expression is associated with neuronal
      apoptosis in an in vivo model of excitotoxicity.
AB  - Platelet activating factor (PAF), an endogenous proinflammatory agent, mediates
      neuronal survival, glutamate release, and transcriptional activation following
      excitotoxin challenge. To determine whether PAF receptor (PAFR) expression is
      altered during excitotoxicity, changes in PAFR mRNA localization were compared
      with markers of neuronal apoptosis and reactive gliosis following systemic
      injection of kainic acid. Data from semi-quantitative RT-PCR, in situ
      hybridization, DNA fragmentation, cellular morphology analysis, and
      immunohistochemistry demonstrate that the localization of PAFR mRNA is altered
      during kainic acid-induced neurodegeneration. While PAFR mRNA is normally
      exhibited by neurons and microglia in rat hippocampus, expression becomes
      restricted to apoptotic neurons and to glia involved in phagocytosing apoptotic
      debris following treatment with excitotoxin. PAFR mRNA is rarely detected in
      surviving neurons. These data provide the first indication that PAFR-expressing
      neurons may be preferentially susceptible to excitotoxic challenge.

PMID- 10203695
TI  - Crm-A, bcl-2 and NDGA inhibit CD95L-induced apoptosis of malignant glioma cells
      at the level of caspase 8 processing.
AB  - Susceptibility to CD95 (Fas/APO-1)-mediated apoptosis in human glioma cells
      depends on CD95 expression and unknown factors that regulate signal transduction.
      Thus, LN-18 cells are highly sensitive to CD95 ligand (CD95L) whereas LN-229
      cells require coexposure to inhibitors of RNA or protein synthesis for induction
      of apoptosis. Here, we report that caspase 8 and 3 activation, poly(ADP
      ribose)polymerase cleavage and apoptosis are inhibited by the lipoxygenase
      inhibitor, nordihydroguaretic acid (NDGA), or ectopic expression of crm-A or bcl
      2. CD95L-induced glioma cell apoptosis does not involve ceramide generation.
      Apoptosis induced by exogenous ceramide resembles CD95-mediated apoptosis in that
      bcl-2 is protective but differs in that NDGA and crm-A have no effect and in that
      cycloheximide (CHX) inhibits rather than potentiates ceramide-induced cell death.
      We conclude that caspase 8 and caspase 3 activation, but not ceramide generation,
      are required for CD95 ligand-induced apoptosis of glioma cells and that bcl-2,
      crm-A and NDGA all act upstream of caspases to inhibit apoptosis.

PMID- 10203696
TI  - Bcl-2 family members in the development and degenerative pathologies of the
      nervous system.
AB  - Neuronal death is an essential feature in the normal development of the nervous
      system and in neurodegenerative states of the adult or ageing brain. Bcl-2 is the
      prototype of a growing family of proteins which control cell death. Many of these
      proteins are expressed in the nervous system during development and in the adult.
      Numerous observations have suggested that this family of proteins plays a central
      role in the control of naturally occurring and pathological neuronal death. In
      this review, I will discuss the possible mechanisms of action of these proteins
      as well as their potential use in treating neurodegenerative diseases.

PMID- 10203697
TI  - Growth factors prevent changes in Bcl-2 and Bax expression and neuronal apoptosis
      induced by nitric oxide.
AB  - Recent studies have shown that nitric oxide (NO) donors can trigger apoptosis of
      neurons, and growth factors such as insulin-like growth factor-1 (IGF-1) and
      basic fibroblast growth factor (bFGF) can protect against NO-induced neuronal
      cell death. The purpose of this study was to elucidate the possible mechanisms of
      NO-mediated neuronal apoptosis and the neuroprotective action of these growth
      factors. Both IGF-1 and bFGF prevented apoptosis induced by NO donors, sodium
      nitroprusside (SNP) or 3-morpholinosydnonimin (SIN-1) in hippocampal neuronal
      cultures. Incubation of neurons with SNP induced caspase-3-like activation
      following downregulation of Bcl-2 and upregulation of Bax protein levels in
      cultured neurons. Treatment of neurons with a bax antisense oligonucleotide
      inhibited the caspase-3-like activation and neuronal death induced by SNP. In
      addition, treatment of neurons with an inhibitor of caspase-3, Ac-DEVD-CHO,
      together with SNP did not affect the changes in the protein levels, although it
      inhibited NO-induced cell death. Pretreatment of cultures with either IGF-1 or
      bFGF prior to NO exposure inhibited caspase-3-like activation together with the
      changes in Bcl-2 and Bax protein levels. These results suggest that the changes
      in Bcl-2 and Bax protein levels followed by caspase-3-like activation are a
      component in the cascade of NO-induced neuronal apoptosis, and that the
      neuroprotective actions of IGF-1 and bFGF might be due to inhibition of the
      changes in the protein levels of the Bcl-2 family.

PMID- 10203698
TI  - Identification of a new caspase homologue: caspase-14.
AB  - Caspases are cysteinyl aspartate-specific proteinases, many of which play a
      central role in apoptosis. Here, we report the identification of a new murine
      caspase homologue, viz. caspase-14. It is most related to human/murine caspase-2
      and human caspase-9, possesses all the typical amino acid residues of the
      caspases involved in catalysis, including the QACRG box, and contains no or only
      a very short prodomain. Murine caspase-14 shows 83% similarity to human caspase
      14. Human caspase-14 is assigned to chromosome 19p13.1. Northern blot analysis
      revealed that mRNA expression of caspase-14 is undetectable in all mouse adult
      tissues examined except for skin, while it is abundantly expressed in mouse
      embryos. In contrast to many other caspase family members, murine caspase-14 is
      not cleaved by granzyme B, caspase-1, caspase-2, caspase-3, caspase-6, caspase-7
      or caspase-11, but is weakly processed into p18 and p11 subunits by murine
      caspase-8. No aspartase activity of murine caspase-14 could be generated by
      bacterial or yeast expression. Transient overexpression of murine caspase-14 in
      mammalian cells did not elicit cell death and did not interfere with caspase-8
      induced apoptosis. In conclusion, caspase-14 is a member of the caspase family
      but no proteolytic or biological activities have been identified so far. The high
      constitutive expression levels in embryos and specific expression in adult skin
      suggest a role in ontogenesis and skin physiology.

PMID- 10203699
TI  - Cow's milk and type I diabetes: the gut immune system deserves attention.

PMID- 10203700
TI  - Bone marrow in atopy and asthma: hematopoietic mechanisms in allergic
      inflammation.

PMID- 10203701
TI  - An innate view of human pregnancy.
AB  - Our understanding of the immunology of pregnancy has been dominated by the fetal
      allograft model and by changes in the maternal-specific immune system. Here,
      Gavin Sacks and colleagues draw attention to substantial and contrasting changes
      in the maternal innate system and hypothesize that its function and that of
      monocytes in particular, has a central role in the maternal-fetal relationship.

PMID- 10203702
TI  - Immune cell signaling defects in lupus: activation, anergy and death.
AB  - Recent studies have identified novel aberrations in antigen receptor-mediated
      signaling events in lymphocytes from patients with systemic lupus erythematosus.
      Here, we propose that in lupus lymphocytes, the receptor-mediated increase in
      protein tyrosine phosphorylation and cytoplasmic free Ca2+ responses, along with
      T-cell receptor zeta chain deficiency, might explain the previously described
      diverse and conflicting immunoregulatory defects in human lupus.

PMID- 10203703
TI  - Phosphorylcholine: friend or foe of the immune system?
AB  - Phosphorylcholine (PC) is a structural component of a variety of prokaryotic and
      eukaryotic pathogens. In some cases, PC in infectious agents can benefit the
      infected host due to its targeting by both the innate and adaptive immune
      responses. However, as discussed here, PC exhibits a surprising range of
      immunomodulatory properties that might be to the detriment of the host.

PMID- 10203704
TI  - Tissue transglutaminase: apoptosis versus autoimmunity.
AB  - Autoimmune diseases are characterized by multiple autoantibodies and/or
      autoreactive T cells that recognize a large number of antigens. Many of these
      antigens undergo extensive post-translational modifications during apoptosis and
      act as substrates for the proapoptotic cystein proteases. Here, Mauro Piacentini
      and Vittorio Colizzi discuss the effects on autoimmunity produced by post
      translational modifications of proteins catalysed by the proapoptotic enzyme
      tissue transglutaminase.

PMID- 10203705
TI  - FHL-1/reconectin: a human complement and immune regulator with cell-adhesive
      function.
AB  - A novel regulator of the alternative complement pathway with functions similar to
      that of factor H has been identified in human plasma. The cDNA encoding this
      factor H-like protein 1 (FHL-1/reconectin) was isolated several years ago. Here,
      Peter Zipfel and Christine Skerka describe functional analyses revealing that
      this novel complement regulatory protein forms a molecular link between immune
      defense and cell adhesion.

PMID- 10203706
TI  - Regional specialization in the mucosal immune system: what happens in the
      microcompartments?
AB  - Mucosal immunity is an important arm of the immune system because it operates in
      tissues involved in everyday infectious defence as well as in tolerance against
      innocuous environmental and dietary antigens. Here, Per Brandtzaeg and colleagues
      discuss compartmentalized regulation of mucosal B cells and mechanisms that might
      explain the strikingly regionalized effector disparity of the human mucosal
      immune system.

PMID- 10203707
TI  - The female X-inactivation mosaic in SLE.

PMID- 10203708
TI  - Reply to Gregersen. and Takeno.

PMID- 10203709
TI  - Turning the immune system on.

PMID- 10203710
TI  - Where have all the T cells gone? Mechanisms of immune evasion by tumors.

PMID- 10203711
TI  - MHC-based diagnostics and therapeutics - clinical applications for disease-linked
      genes.

PMID- 10203712
TI  - Major histocompatibility complex: from genes to function.

PMID- 10203713
TI  - Research directions in paroxysmal nocturnal hemoglobinuria.

PMID- 10203715
TI  - Faces and phases of human CD8 T-cell development.

PMID- 10203714
TI  - Would suicide gene therapy solve the 'T-cell dilemma' of allogeneic bone marrow
      transplantation?

PMID- 10203716
TI  - Immunotherapy with CTLs restricted by nonself MHC.

PMID- 10203717
TI  - The key role of PU.1/SPI-1 in B cells, myeloid cells and macrophages.

PMID- 10203718
TI  - Antigen-based immunotherapy for autoimmune disease: from animal models to humans?
AB  - Insights into tolerance and autoimmune processes have led to novel
      immunotherapeutics for inhibiting autoimmune disease in animal models. However,
      recent studies question the immune basis of some of these therapeutic strategies
      and raise concerns about their efficacy and safety. Here, we discuss the
      feasibility of extending the success of antigen-based immunotherapeutics for T
      cell-mediated autoimmune diseases from animal models to humans.

PMID- 10203719
TI  - Receptor editing during affinity maturation.

PMID- 10203720
TI  - DC-based cancer immunotherapy: the sequel.

PMID- 10203725
TI  - Tandem mass spectrometry: the tool of choice for diagnosing inborn errors of
      metabolism.

PMID- 10203726
TI  - Visualizing gallstone formation.

PMID- 10203727
TI  - Blocking HIV-1 infection with intrakines.

PMID- 10203730
TI  - Biochemistry versus molecular medicine: what should we be teaching our medical
      students?

PMID- 10203731
TI  - Integrating molecular medicine into the medical school curriculum.

PMID- 10203732
TI  - Medical education: catering for the carers as well as the innovators.

PMID- 10203733
TI  - Xenotransplantation and cell therapy: progress and controversy. IBC's 4th
      International Conference on Xenotransplantation and Cell Therapy. Boston, MA,
      USA, 10-11 December 1998.

PMID- 10203734
TI  - The palmoplantar keratodermas: much more than palms and soles.
AB  - The inherited palmoplantar keratodermas (PPKs) are a diverse and often clinically
      confusing branch of the genetic skin diseases. As the name suggests, the lesions
      of PPK primarily affect the palms and soles of the feet, although a number of the
      PPKs are also associated with a genetic predisposition to other conditions,
      including cancer, hearing loss and heart failure. The mapping and identification
      of genes that underlie the PPKs reveal new insights into the biological
      interactions of the structural components of the palmoplantar epidermis and
      further our understanding of epidermal disease. More significantly, by
      genetically characterizing the PPKs, genes that have a role in life-threatening
      disorders might also be identified.

PMID- 10203735
TI  - Applications of telomerase research in the fight against cancer.
AB  - Telomerase, an enzyme that confers immortality upon cells and that is active in
      the majority of human tumors, has emerged as a powerful new marker and potential
      prognostic indicator and therapeutic target for cancer. Furthermore,
      investigations into the biology of telomerase have revealed important clues into
      the causes of cell death and have made progress toward answering one of the most
      important questions of cancer research - what gives a tumor cell an advantage
      over normal cells? In this article, we present the current state of telomerase
      research and critically assess both its potential and the pitfalls of its
      application in cancer diagnosis and treatment.

PMID- 10203736
TI  - The molecular pathogenesis of endotoxic shock and organ failure.
AB  - Sepsis is still associated with a high mortality rate. Septic shock and
      sequential multiple organ failure have a strong correlation with poor outcome.
      Lipopolysaccharide (LPS) plays a pivotal role in the initiation of host responses
      to Gram-negative infection. A number of mediators, such as cytokines, nitric
      oxide and eicosanoids, are responsible for most of the manifestations caused by
      LPS, and circulatory failure, leukocyte-induced tissue injury and coagulation
      disorder appear to be critical determinants in the development of sequential
      organ failure. Although several anti-LPS or anti-cytokine clinical trials have
      been attempted, none of them has so far been successful.

PMID- 10203737
TI  - The diagnosis and treatment of osteoporosis: future prospects.
AB  - Osteoporosis is a common disease that affects millions of patients throughout the
      world. We anticipate that both the diagnosis and the treatment of this disease
      will be revolutionized by the integration of genomics and informatics. It is
      predicted that a genetic algorithm will be developed to identify at-risk patients
      before they develop osteoporosis, so that preventive measures can be instituted.
      The sequencing of the human genome will lead to revolutionary advances in at
      least three areas of osteoporosis therapy: small molecule therapy, protein
      therapy and gene therapy. One area of focus for future therapeutics in
      osteoporosis will be on osteogenic agents, which should have a high likelihood of
      success because the skeleton has the innate capacity to regenerate itself.

PMID- 10203738
TI  - Ups and downs on the road to an HIV vaccine.

PMID- 10203739
TI  - Rapid update 

PMID- 10203740
TI  - Q fever vaccine on trial for type I diabetes.

PMID- 10203741
TI  - Human neural stem cells on trial for Parkinson's disease.

PMID- 10203745
TI  - Joint efforts: tackling arthritis using gene therapy. First International Meeting
      on the Gene Therapy of Arthritis and Related Disorders. Bethesda, MD, USA, 2-3
      December 1998.

PMID- 10203746
TI  - Changing focus: applying antisense to nuclear medicine imaging.

PMID- 10203747
TI  - Prenatal gene therapy: can the technical hurdles be overcome?
AB  - Fifty years ago, a medical breakthrough in the prenatal diagnosis of genetic
      disorders was made with the introduction of amniocentesis. Until recently, there
      was little hope that diseases diagnosed in utero could be treated before birth.
      Today, prenatal gene therapy is emerging as a new concept for treating pre- and
      postnatal manifestations of genetic diseases and developmental disorders.
      Research studies have generated a degree of optimism by demonstrating the
      feasibility of fetal gene transfer. Nevertheless, enthusiasm is tempered by the
      considerable technical and ethical issues raised by such studies. Undoubtedly,
      the future of prenatal gene transfer as a therapeutic approach for birth defects
      mostly depends on addressing and overcoming these concerns.

PMID- 10203748
TI  - Radiation, DNA damage and cancer.
AB  - The characterization of the rare, radiation-sensitive and cancer-prone syndromes,
      ataxia telangiectasia and Nijmegen breakage syndrome, has demonstrated that
      genetic predisposition increases the risk of developing cancer after exposure to
      ionizing radiation (IR). Molecular analyses of these disorders provide valuable
      insights into the normal function of these two gene products in the cellular
      response to IR-induced DNA damage. Their contribution to a cellular
      radiosensitive phenotype and their role in sporadic cancers can now be fully
      assessed. For example, the gene ataxia telangiectasia mutated (ATM) has recently
      been shown to be a tumour suppressor gene in T-cell prolymphocytic leukaemia, and
      there is increasing evidence that individuals with one mutated ATM or Nijmegen
      breakage syndrome (NBS1) allele have an increased predisposition to cancer.

PMID- 10203749
TI  - Towards gene therapy of diabetes mellitus.
AB  - A definitive treatment for diabetes mellitus will be one that maintains a normal
      blood glucose concentration in the face of fluctuating dietary intake. To
      accomplish this, there must be mechanisms to sense the amount of blood glucose
      coupled to rapid release of the right amount of insulin. While mechanical devices
      to accomplish this are being developed, ultimately the best approach is likely to
      be based on genetic modification of cells. These could be pancreatic beta-cells,
      which are the only cells that produce insulin, or other cells that are involved
      in the pathogenesis of diabetes. Although definitive treatment of diabetes using
      genetically modified cells is a long-term goal, much progress is being made. This
      review discusses various approaches to modifying cells genetically, both in vitro
      and in vivo, for the treatment of diabetes.

PMID- 10203750
TI  - E-cadherin downregulation in cancer: fuel on the fire?
AB  - The development, maintenance and repair of tissue requires an exquisite balance
      between cell proliferation, cell adhesion and cell motility. Equally, tumour
      initiation and progression are characterized by not only the abnormal expression
      of genes involved in cell proliferation and survival but also by genes
      responsible for the control of cell adhesion and cell motility. Central to the
      process of cell-cell adhesion in epithelial tissues is E-cadherin. Loss of E
      cadherin function in tumours results in the rapid progression of relatively
      benign adenomas to invasive, metastatic carcinomas. Germline mutation of the E
      cadherin gene predisposes to diffuse, poorly differentiated gastric cancer, and
      its downregulation in sporadic tumours is associated with poor clinical
      prognosis.

PMID- 10203752
TI  - Ribosome recruitment and scanning: what's new?

PMID- 10203751
TI  - HLA class I antigen downregulation in human cancers: T-cell immunotherapy revives
      an old story.
AB  - Human leukocyte antigen (HLA) class I molecule downregulation occurs frequently
      in many cancers, and this abnormality might adversely affect the clinical course
      of cancer and the outcome of T-cell-based immunotherapy. Mutations in the HLA
      class I genes themselves, abnormalities in their regulation and/or defects in HLA
      class I-dependent antigen processing can underlie HLA class I downregulation.
      These mutations modulate the susceptibility of tumor cells to in vitro lysis by
      cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Immune selection of
      CTL- and NK-cell-resistant tumor cells might explain the rapid progression and
      poor prognosis of cancers that exhibit HLA class I downregulation. These findings
      provide compelling evidence that HLA class I downregulation represents a
      significant challenge for the successful application of T-cell-based
      immunotherapy of cancer.

PMID- 10203753
TI  - Metabolic symbiosis at the origin of eukaryotes.
AB  - Thirty years after Margulis revived the endosymbiosis theory for the origin of
      mitochondria and chloroplasts, two novel symbiosis hypotheses for the origin of
      eukaryotes have been put forward. Both propose that eukaryotes arose through
      metabolic symbiosis (syntrophy) between eubacteria and methanogenic Archaea. They
      also propose that this was mediated by interspecies hydrogen transfer and that,
      initially, mitochondria were anaerobic. These hypotheses explain the mosaic
      character of eukaryotes (i.e. an archaeal-like genetic machinery and a
      eubacterial-like metabolism), as well as distinct eukaryotic characteristics
      (which are proposed to be products of symbiosis). Combined data from comparative
      genomics, microbial ecology and the fossil record should help to test their
      validity.

PMID- 10203754
TI  - The SIS domain: a phosphosugar-binding domain.

PMID- 10203755
TI  - A relationship betweena DNA-repair/recombination nuclease family and archaeal
      helicases.

PMID- 10203756
TI  - Separating sister chromatids.
AB  - Loss of cohesion between sister chromatids triggers their segregation during
      anaphase. Recent work has identified both a cohesin complex that holds sisters
      together and a sister-separating protein, separin, that destroys cohesion.
      Separins are bound by inhibitory proteins whose proteolysis at the metaphase
      anaphase transition is mediated by the anaphase-promoting complex and its
      activator protein CDC20 (APCCDC20). When chromosomes are misaligned, a
      surveillance mechanism (checkpoint) blocks sister separation by inhibiting
      APCCDC20. Defects in this apparatus are implicated in causing aneuploidy in human
      cells.

PMID- 10203757
TI  - Bacterial solutions to the iron-supply problem.
AB  - The insolubility of Fe3+ necessitates special mechanisms for iron acquisition in
      most organisms. Bacteria use siderophores to chelate Fe3+ and iron in heme,
      hemoglobin, transferrin and lactoferrin, and employ novel mechanisms for receptor
      dependent iron transport and iron-regulated gene expression. These mechanisms
      involve transfer of energy from the cytoplasmic membrane to the outer membrane to
      drive active transport and might induce transcription of transport genes by
      transmitting a signal from the cell surface.

PMID- 10203758
TI  - Mechanisms of lipid-body formation.
AB  - Most organisms transport or store neutral lipids as lipid bodies - lipid droplets
      that usually are bounded by specific proteins and (phospho)lipid. Neutral-lipid
      bodies vary considerably in their morphology and are associated with an extremely
      diverse range of proteins. However, the mechanisms by which they are generated in
      plants, animals and microorganisms appear to share many common features: lipid
      bodies probably arise from microdomains of the endoplasmic reticulum (or the
      plasma membrane in prokaryotes) that contain lipid-biosynthesis enzymes, and
      their synthesis and size appear to be controlled by specific protein components.

PMID- 10203759
TI  - Overcoming inhibitions: subversion of CKI function by viral cyclins.
AB  - DNA tumour viruses deregulate the mammalian cell cycle to provide a better
      environment for their replication. Studies of such deregulation have led to the
      identification of key regulatory steps that normally control the G1-S phase
      transition of the cell cycle. The balance between the activities of G1-specific
      cyclin-CDK complexes and their inhibitors is critical. Recent studies suggest
      that certain herpesviruses disrupt this balance: the viruses encode a cyclin that
      generates active complexes even in the presence of high inhibitor levels.

PMID- 10203763
TI  - Bioinformatics, pharma and farmers.

PMID- 10203760
TI  - One chromosome: one DNA molecule.

PMID- 10203764
TI  - Screensavers: trends in high-throughput analysis.

PMID- 10203766
TI  - A guide to the WWW.

PMID- 10203765
TI  - The sheep and the goats.

PMID- 10203767
TI  - An overview of biotechnology in Korea.
AB  - During the 1980s and 1990s, Korea has invested heavily in biotechnology research
      and development, with the aim of becoming a leading nation in this field. It is
      important to understand the historical progress of this development in order to
      appreciate the current state of biotechology in Korea. However, it is equally
      important to know what research is currently being planned and carried out, and
      by whom.

PMID- 10203768
TI  - Combinatorial approaches to materials discovery.
AB  - Using a mixture of scientific intuition, iteration and serendipity, combinatorial
      materials science is an approach to the discovery and study of new materials that
      combines high-speed chemical synthesis, high-throughput screening and high
      capacity information processing to create, analyse and interpret large numbers of
      new and diverse material compositions. Technology has now been developed that
      makes this powerful integration possible. The classes of materials under
      investigation include catalysts, luminescent, optical, magnetic and dielectric
      materials, and structural polymers.

PMID- 10203769
TI  - Directed evolution of industrial enzymes.

PMID- 10203770
TI  - Display technologies expand their horizons.

PMID- 10203771
TI  - The Biotechnology Patent Directive is approved at last!

PMID- 10203772
TI  - Spatially resolved force spectroscopy of biological surfaces using the atomic
      force microscope.
AB  - The spatial distribution of intermolecular forces governs macromolecular
      interactions. The atomic force microscope, a relatively new tool for
      investigating interaction forces between nanometer-scale objects, can be used to
      produce spatially resolved maps of the surface or material properties of a
      sample; these include charge density, adhesion and stiffness, as well as the
      force required to break specific ligand-receptor bonds. Maps such as these will
      provide fundamental insights into biological structure and will become an
      important tool for characterizing technologically important biological systems.

PMID- 10203773
TI  - The complexities of DNA computation.
AB  - Over the past few years, a handful of insightful researchers have bridged the gap
      between biological computing theory and actual DNA-based computation. By using
      ingenious encoding techniques and clever molecular-biological manipulations,
      simple versions of computationally complex problems have been experimentally
      approached or resolved. However, the technical problems revealed during the
      execution of these scientific set pieces make it unlikely that DNA will ever
      rival silicon for the solution of any real-world problem.

PMID- 10203774
TI  - Applying neural networks as software sensors for enzyme engineering.
AB  - The on-line control of enzyme-production processes is difficult, owing to the
      uncertainties typical of biological systems and to the lack of suitable on-line
      sensors for key process variables. For example, intelligent methods to predict
      the end point of fermentation could be of great economic value. Computer-assisted
      control based on artificial-neural-network models offers a novel solution in such
      situations. Well-trained feedforward-backpropagation neural networks can be used
      as software sensors in enzyme-process control; their performance can be affected
      by a number of factors.

PMID- 10203775
TI  - Recent biotechnological developments in the use of peroxidases.
AB  - Peroxidases are ubiquitous oxidoreductases that use hydrogen peroxide or alkyl
      peroxides as oxidants. Advances have recently been made in using them to prepare,
      under mild and controlled conditions, chiral organic molecules that are valuable
      for the chemoenzymatic synthesis of a wide range of useful compounds. Horseradish
      peroxidase can be converted into a peroxygenative enzyme by molecular
      engineering. Chloroperoxidase, the most versatile peroxidase, behaves like a
      'true' monooxygenase in sulfoxidations with molecular oxygen and an external
      reductant, with substantial increases in enantioselectivity and enzyme stability.

PMID- 10203779
TI  - 800 oscillations per cycle.

PMID- 10203776
TI  - Large-scale production of pharmaceutical-grade plasmid DNA for gene therapy:
      problems and bottlenecks.
AB  - Gene therapy is a promising process for the prevention, treatment and cure of
      diseases such as cancer, acquired immunodeficiency syndrome (AIDS) and cystic
      fibrosis. One of the methods used to administer therapeutic genes is the direct
      injection of naked or lipid-coated plasmid DNA, but this requires considerable
      amounts of plasmid DNA. There are several problems and bottlenecks associated
      with the design and operation of large-scale processes for the production of
      pharmaceutical-grade plasmid DNA for gene therapy.

PMID- 10203778
TI  - Cilia whip up left-right asymmetry.

PMID- 10203780
TI  - Special-interest subgroups at the ASCB: Tau protein in neurodegenerative disease.
AB  - The annual meeting of the American Society for Cell Biology (ASCB) is a large and
      diverse gathering. At last year's meeting**The American Society for Cell Biology
      38th Annual Meeting, San Francisco, USA; 12-16 December, 1998. Program chair:
      Jennifer Lippincott-Schwartz., there were over 8000 attendees, and the topics
      discussed covered many areas of cell biology. It would be impossible to cover the
      entire meeting within a trends in CELL BIOLOGY report, so instead we are focusing
      on an aspect of it that provided some of the most interesting and fruitful
      discussions. On Saturday afternoon, before the main symposia began, there were 11
      special-interest subgroup meetings. The atmosphere at these meetings was
      informal, and they encouraged open and frank discussion of data and issues. This
      report provides a brief summary of the discussions at seven of the special
      interest subgroup meetings.

PMID- 10203781
TI  - Special-interest subgroups at the ASCB: Nuclear dynamics at mitosis.
AB  - The annual meeting of the American Society for Cell Biology (ASCB) is a large and
      diverse gathering. At last year's meeting**The American Society for Cell Biology
      38th Annual Meeting, San Francisco, USA; 12-16 December, 1998. Program chair:
      Jennifer Lippincott-Schwartz., there were over 8000 attendees, and the topics
      discussed covered many areas of cell biology. It would be impossible to cover the
      entire meeting within a trends in CELL BIOLOGY report, so instead we are focusing
      on an aspect of it that provided some of the most interesting and fruitful
      discussions. On Saturday afternoon, before the main symposia began, there were 11
      special-interest subgroup meetings. The atmosphere at these meetings was
      informal, and they encouraged open and frank discussion of data and issues. This
      report provides a brief summary of the discussions at seven of the special
      interest subgroup meetings.

PMID- 10203784
TI  - Careers-perspective interview.

PMID- 10203786
TI  - PERKing up the ER stress response 

PMID- 10203785
TI  - PTEN: a tumour suppressor that functions as a phospholipid phosphatase.
AB  - The tumour suppressor PTEN has been implicated in a large number of human tumours
      and is conserved from humans to worms. Characterization of PTEN protein showed
      that it is a phosphatase that acts on proteins and on 3-phosphorylated
      phosphoinositides, including phosphatidylinositol (3,4,5)-trisphosphate, and can
      therefore modulate signal-transduction pathways that involve lipid second
      messengers. Recent results indicate that at least part of its role is to regulate
      the activity of the serine/threonine kinase AKT/PKB, and thus influence cell
      survival signalling. This article discusses the function of PTEN and how this
      could be linked to its activity as a tumour suppressor.

PMID- 10203787
TI  - The golgi bypassed 

PMID- 10203788
TI  - Serum theorem 

PMID- 10203789
TI  - Regulation of protein biogenesis at the endoplasmic reticulum membrane.
AB  - The biogenesis of most secretory and membrane proteins involves targeting the
      nascent protein to the endoplasmic reticulum (ER), translocation across or
      integration into the ER membrane and maturation into a functional product. The
      essential machinery that directs these events for model secretory and membrane
      proteins has been identified, shifting the focus of studies towards the molecular
      mechanisms by which these core components function. By contrast, regulatory
      mechanisms that allow certain proteins to serve multiple functions within a cell
      remain entirely unexplored. This article examines each stage of protein
      biogenesis as a potential site of regulation that could be exploited by the cell
      to effectively increase the diversity of functional gene expression.

PMID- 10203790
TI  - RGS proteins: more than just GAPs for heterotrimeric G proteins.
AB  - Members of the newly described RGS family of proteins have a common RGS domain
      that contains GTPase-activating activity for many Galpha subunits of
      heterotrimeric G proteins. Their ability to dampen signalling via Galphai-,
      Galphaq- and Galpha12/13-coupled pathways makes them crucial players in mediating
      the multitude of cellular processes controlled by heterotrimeric G proteins. Some
      RGS proteins also contain additional motifs that link them to other signalling
      networks, where they constitute effector-type molecules. This review summarizes
      recent findings on RGS proteins, especially those that implicate RGS proteins in
      more than just enhancing the GTPase activity of their Galpha subunit targets.

PMID- 10203792
TI  - The SAC, EEA1, rab5 and endosome fusion 

PMID- 10203791
TI  - The subapical compartment: a novel sorting centre?
AB  - Establishment of plasma membrane polarity involves numerous intracellular sorting
      events. In the past few years, it has become apparent that there is a subapical,
      non-Golgi compartment located in the hub of the sorting pathways involved. This
      'subapical compartment', which probably consists of a heterogeneous subset of
      functionally distinct domains related to endosomes, contains some well
      characterized components involved in polarity-dependent sorting and targeting of
      proteins and lipids. This article discusses the evidence supporting the existence
      of such a compartment, its biogenesis and its role in cell polarity.

PMID- 10203793
TI  - Targeting vesicles to specific sites on the plasma membrane: the role of the
      sec6/8 complex.
AB  - The delivery of secretory vesicles to appropriate docking and fusion sites on the
      plasma membrane is crucial for many cellular functions, including formation of
      synapses, exocytosis of neurotransmitter, establishment and maintenance of cell
      polarity, cell growth and plasma membrane wound healing. Cell-biological, genetic
      and biochemical approaches have identified crucial proteins and protein
      interactions important for vesicle docking and fusion. However, a description of
      the molecular mechanisms underlying vesicle targeting to specific membrane-fusion
      sites remains elusive. This review discusses a set of proteins that might direct
      vesicles to specific domains of the plasma membrane.

PMID- 10203794
TI  - High-resolution electron cryomicroscopy of macromolecular assemblies.
AB  - Electron cryomicroscopy is a high-resolution imaging technique that is
      particularly appropriate for the structural determination of large macromolecular
      assemblies, which are difficult to study by X-ray crystallography or NMR
      spectroscopy. For some biological molecules that form two-dimensional crystals,
      the application of electron cryomicroscopy and image reconstruction can help
      elucidate structures at atomic resolution. In instances where crystals cannot be
      formed, atomic-resolution information can be obtained by combining high
      resolution structures of individual components determined by X-ray
      crystallography or NMR with image-derived reconstructions at moderate resolution.
      This can provide unique and crucial information on the mechanisms of these
      complexes. Finally, image reconstructions can be used to augment X-ray studies by
      providing initial models that facilitate phasing of crystals of large
      macromolecular machines such as ribosomes and viruses.

PMID- 10203796
TI  - Pictures in cell biology. Autophagosomes in yeast.

PMID- 10203795
TI  - Archaea: from genomics to physiology and the origin of life.

PMID- 10203797
TI  - Careers-perspective interview.

PMID- 10203799
TI  - Plant genomics takes root, branches out.
AB  - For the past nine years, an international consortium of researchers have
      collaborated on a project to provide a full set of genomics tools for the model
      plant species Arabidopsis thaliana. Among the goals of this project were the
      complete sequence of the Arabidopsis genome, which may be completed in the year
      2000, four years ahead of schedule. Arabidopsis was an appropriate choice as the
      first target of plant genomics because of its excellent genetics, outstanding
      research community and small genome size. Until very recently, it appeared that
      comprehensive high-throughput plant genomics in the public sector would largely
      begin and end with Arabidopsis. Over the past two years, this situation has
      changed completely.

PMID- 10203800
TI  - Gene targeting and somatic cell genetics--a rebirth or a coming of age?
AB  - A number of recent advances have significantly facilitated gene targeting in
      somatic cells. Gene targeting can now be performed with the same ease and
      efficiency in somatic cells as in murine embryonic stem cells. Rigorous genetic
      analyses can therefore be applied for the first time to the large number of
      excellent human cell culture systems. These tools will be important in areas
      where rodent models do not adequately represent human biology.

PMID- 10203801
TI  - Mitochondrial DNA--all things bad?
AB  - Mutations in mitochondrial DNA (mtDNA) are undoubtedly associated with a diverse
      spectrum of human disorders. More controversially, it has been claimed that they
      accumulate during ageing, and that they are responsible for an age-related
      decline in bioenergetic function and tissue viability. Here, we review the
      evidence for this assertion, concluding that claims for the age-accumulation of
      mtDNA mutations are based largely on non-quantitative methods, and that no clear,
      functional deficit of mitochondrial respiration has been shown to result from
      such lesions in aged individuals. The mitochondrial theory of ageing, however
      attractive in principle, is supported by very little hard evidence.

PMID- 10203802
TI  - The high cost of living. American Association for Cancer Research Special
      Conference: endogenous sources of mutations, Fort Myers, Florida, USA, 11-15
      November 1998.

PMID- 10203804
TI  - Viruses making plants greener.

PMID- 10203803
TI  - Mono-allelic expression of genes in simple eukaryotes.

PMID- 10203805
TI  - Turn back the clock.

PMID- 10203806
TI  - Making sense of the COP9 signalosome. A regulatory protein complex conserved from
      Arabidopsis to human.
AB  - The COP9 signalosome, once defined as a repressor complex of light-activated
      development in Arabidopsis, has recently been found in humans and is probably
      present in most multicellular organisms. The COP9 signalosome is closely related
      to the lid sub-complex of the 26S proteasome in structural composition and
      probably shares a common evolutionary ancestor. A multifaceted role of the COP9
      signalosome in cell-signaling processes is hinted at by its associated novel
      kinase activity, as well as the involvement of its subunits in regulating
      multiple cell-signaling pathways and cell-cycle progression. The molecular
      genetic studies in Arabidopsis suggest that the complex functions as part of a
      highly conserved regulatory network, whose physiological role in animals remains
      to be determined.

PMID- 10203807
TI  - Animal evolution. The end of the intermediate taxa?
AB  - Contrary to general belief, there has not been a reliable, global phylogeny of
      animals at hand within the past few decades. Recent progress in molecular
      phylogeny is rapidly changing the situation and has provided trees that
      constitute a reference frame for discussing the still controversial evolution of
      body plans. These trees, once purged of their possible artefacts, have already
      yielded confirmation of traditional, anatomically based, phylogenies as well as
      several new and quite significant results. Of these, one of the most striking is
      the disappearance of two superphyla (acoelomates such as flatworms,
      pseudocoelomates such as nematodes) previously thought to represent grades of
      intermediate complexity between diploblasts (organisms with two germ layers) and
      triploblasts (organisms with three germ layers). The overall image now emerging
      is of a fairly simple global tree of metazoans, comprising only a small number of
      major branches. The topology nicely accounts for the striking conservation of
      developmental genes in all bilaterians and suggests a new interpretation of the
      'Cambrian explosion' of animal diversity.

PMID- 10203808
TI  - Telomerase activation. One step on the road to cancer?
AB  - Ever since the discovery that telomeres are short in cancer cells and telomerase
      is activated in immortal cells, telomerase has been an oncogene wannabe.
      Oncogenes have been the glamour genes of molecular biology for 20 years,
      garnering flashy headlines and name recognition. More recently, tumor-suppressor
      genes have joined oncogenes on center stage. Recent evidence has shown that MYC
      upregulates the catalytic subunit of telomerase, TERT, and that TERT cooperates
      with HPV E7 in cell immortalization. This evidence now supports the placement of
      telomerase among the cancer gene elite.

PMID- 10203809
TI  - Neuronal guidance. A genetic perspective.
AB  - Remarkable advances have been made recently to identify the molecules required
      for the development of neural connections within the brain. A range of ligands
      and receptors have been uncovered that guide extending neurons to appropriate
      targets and away from inappropriate areas. These molecules point to the
      signalling mechanisms that guide the neurons and provide entry points for the
      further dissection of this process. Here I highlight the part genetic screens and
      analyses have played in revealing some of the key players in neuronal guidance.

PMID- 10203810
TI  - Towards an in silico analysis of transcription patterns.

PMID- 10203812
TI  - Revising the selfish DNA hypothesis: new evidence on accumulation of transposable
      elements in heterochromatin.
AB  - The bulk of the eukaryotic genome is composed of families of repetitive sequences
      that are genetically silent and exhibit various types of instability.
      Transposable elements (TEs) are particularly common in heterochromatic regions of
      the genome - a location where TEs might do less damage to their host. Recent
      advances suggest that the relationship between TEs and heterochromatin might not
      be quite so straightforward.

PMID- 10203813
TI  - Proteolipid protein gene: Pelizaeus-Merzbacher disease in humans and
      neurodegeneration in mice.
AB  - The dosage of the myelin gene and mutant forms of the protein can affect the CNS
      and PNS. Pelizaeus-Merzbacher disease (PMD) is a myelin disorder of the CNS that
      arises from both mutational mechanisms. Investigating the molecular basis of PMD
      in patients and animal models is furthering our understanding of the disease,
      dosage sensitivity and proteolipid protein function during myelinogenesis.

PMID- 10203814
TI  - Cryopreservation of mouse spermatozoa: double your mouse space.
AB  - Cryopreservation of mouse germplasm is an important tool to secure, archive and
      distribute mouse lines of different origin. While embryo freezing has been
      standard procedure for many years, major advantages in freezing spermatozoa have
      been made recently that open new opportunities for management of mouse colonies.

PMID- 10203815
TI  - Why genome analysis?

PMID- 10203816
TI  - Errors in genome annotation.

PMID- 10203817
TI  - Molecular evolutionary evidence that H19 mRNA is functional.

PMID- 10203818
TI  - An ethical collaboration. Ethics in Human Procreation, Genetic Diagnosis and
      Therapy, Sheffield, UK, 7-10 January 1999.

PMID- 10203819
TI  - Expressive genomics. Human Gene Expression Mapping, (HUGO ESF), Paris, France, 21
      22 December 1998.

PMID- 10203820
TI  - Are scs and scs' 'neutral' chromatin domain boundaries of the locus?

PMID- 10203821
TI  - Pseudomonas pathogenicity.

PMID- 10203822
TI  - DPP on the brinker.

PMID- 10203823
TI  - Non-conventional infectious elements in filamentous fungi.
AB  - Old data (most often in French) described phenomena involving non-conventional
      infectious factors in filamentous fungi. Recently, it was shown that two yeast
      cytoplasmic determinants are similar to known mammalian prions, in that their
      different states are attributed to conformational changes of normal cellular
      proteins. In the light of this discovery, fungal elements are now being
      reconsidered. This review presents four elements that affect vegetative
      incompatibility, conidiogenesis, morphology and cell growth. Recently, one
      element has been shown to be a prion analogue. The status of the others is not
      clear. We consider the view that non-conventional inheritance might be initiated
      by the appearance, in the cytoplasm, of a metabolite or a macromolecule whose
      production involves a positive regulatory loop.

PMID- 10203824
TI  - Signaling specificity: the RTK/RAS/MAP kinase pathway in metazoans.
AB  - The molecular basis by which commonly used signaling pathways are able to elicit
      tissue-specific responses in multicellular organisms is an important yet poorly
      understood problem. In this review, we use the receptor tyrosine kinase
      (RTK)/RAS/MAP kinase signaling cascade as a model to discuss various hypotheses
      that have been proposed to explain signaling specificity. Specificity can arise
      at the level of the receptor, through the modulation of signaling kinetics,
      through the interaction of different signaling pathways, and at the level of
      downstream signaling components. Mechanisms of specificity used by the
      RTK/RAS/MAP kinase signaling pathway might apply to other signaling pathways as
      well, and might help explain how multicellular organisms are able to generate
      tissues of diverse forms and functions from a small set of common signaling
      pathways.

PMID- 10203825
TI  - Chemosensation: molecular mechanisms in worms and mammals.
AB  - Communication with the environment and other animals through chemical cues is an
      essential process for the survival of many multicellular organisms. Specialized
      signal transduction pathways are employed in chemodetection and the
      transformation of information into the electrical signals that elicit behaviors.
      In organisms as diverse as mice and nematodes, similar molecules are involved in
      the odorant signaling pathways. Studying the mechanisms of signal transduction in
      these two systems using biochemical, molecular and genetic approaches has
      elucidated pathways for odor perception and the roles of specific proteins and
      second messenger molecules in the signaling cascades.

PMID- 10203826
TI  - T-box genes: what they do and how they do it.
AB  - Brachyury is the founder member of the T-box family of transcription factors,
      which is characterized by a DNA-binding domain of approximately 200 amino acids.
      Members of the T-box gene family play important roles in the development of both
      vertebrate and invertebrate embryos, including the control of gastrulation,
      development of the heart, and perhaps even the decision as to whether to form arm
      or leg. An understanding of how the T-box genes act requires analysis of how
      their expression is controlled, identification of their target genes, and an
      insight into how different family members exert different effects.

PMID- 10203827
TI  - Comparison of gene indexing databases.

PMID- 10203830
TI  - Gene capture in Vibrio cholerae.

PMID- 10203831
TI  - Gene capture in : Response.

PMID- 10203832
TI  - Exploring a novel perspective on pathogenic relationships.

PMID- 10203833
TI  - Exploring a novel perspective on pathogenic relationships: Response.

PMID- 10203834
TI  - Understanding influenza virus pathogenicity.

PMID- 10203835
TI  - Septic shock caused by gram-positive bacteria.

PMID- 10203836
TI  - Microbial genomics.

PMID- 10203837
TI  - It's a knockout.

PMID- 10203838
TI  - Clostridium perfringens: toxinotype and genotype.
AB  - Clostridium perfringens is a ubiquitous pathogen that produces many toxins and
      hydrolytic enzymes. Because the toxin-encoding genes can be located on
      extrachromosomal elements or in variable regions of the chromosome, several
      pathovars have arisen, each of which is involved in a specific disease. Pathovar
      identification is required for a precise diagnosis of associated pathologies and
      to define vaccine requirements. For these purposes, toxin genotyping is more
      reliable than the classical toxinotyping.

PMID- 10203839
TI  - Bacterial tellurite resistance.
AB  - Tellurium compounds are used in several industrial processes, although they are
      relatively rare in the environment. Genes associated with tellurite resistance
      (TeR) are found in many pathogenic bacteria. Tellurite can be detoxified through
      interactions with cellular thiols, such as glutathione, or a methyltransferase
      catalyzed reaction, although neither process appears involved in plasmid-mediated
      TeR.

PMID- 10203840
TI  - Signalling pathways in two-component phosphorelay systems.
AB  - Two-component systems are characterized by phosphotransfer reactions involving
      histidine and aspartate residues in highly conserved signalling domains. Although
      the basic principles of signal transduction by these systems have been
      elucidated, several important aspects, such as their integration into more
      complex cellular regulatory networks and the molecular basis of the specificity
      of signal transduction, remain unknown.

PMID- 10203841
TI  - Selection of drug-resistant HIV.
AB  - Resistance to antiretroviral drugs by HIV develops from competition among several
      different virus variants within an individual. Recent studies have measured the
      changing proportions of HIV populations, which differ by single nucleic acids,
      under the selective pressures exerted by the addition or removal of
      antiretroviral drugs.

PMID- 10203842
TI  - Domain organization and oligomerization among H-NS-like nucleoid-associated
      proteins in bacteria.
AB  - The bacterial nucleoid-associated proteins H-NS and StpA can form homomeric or
      heteromeric complexes, a parallel with protein HU. Thus, functional modulation of
      H-NS and StpA by one another and by other proteins with appropriate interaction
      domains is possible. This has implications for bacterial pathogenesis and
      adaptation to environmental stress.

PMID- 10203843
TI  - The ecological role of bacteriocins in bacterial competition.
AB  - Bacteriocins are an abundant class of antimicrobial molecules that appear to
      mediate population dynamics within species. The bacteriocins of Escherichia coli
      have served as a model for exploring the ecological role of these potent toxins.
      Studies suggest that colicins provide a competitive edge in nutrient-poor
      environments and that there might be a trade-off between the costs and benefits
      of colicin production.

PMID- 10203848
TI  - Signals that go with the flow.

PMID- 10203849
TI  - Is the short-latency dopamine response too short to signal reward error?
AB  - Unexpected stimuli that are behaviourally significant have the capacity to elicit
      a short-latency, short-duration burst of firing in mesencephalic dopaminergic
      neurones. An influential interpretation of the experimental data that
      characterize this response proposes that dopaminergic neurones have a crucial
      role in reinforcement learning because they signal error in the prediction of
      future reward. In this article we propose a different functional role for this
      'short-latency dopamine response' in the mechanisms that underlie associative
      learning. We suggest that the initial burst of dopaminergic-neurone firing could
      represent an essential component in the process of switching attentional and
      behavioural selections to unexpected, behaviourally important stimuli. This
      switching response could be a crucial prerequisite for associative learning and
      might be part of a general short-latency response that is mediated by
      catecholamines and prepares the organism for an appropriate reaction to
      biologically significant events. Any act which in a given situation produces
      satisfaction becomes associated with that situation so that when the situation
      recurs the act is more likely than before to recur also. E.L. Thorndike (1911) 1.

PMID- 10203850
TI  - From grasping to speech: imitation might provide a missing link.

PMID- 10203851
TI  - From grasping to speech: imitation might provide a missing link: reply 

PMID- 10203852
TI  - Fifty years of a command neuron: the neurobiology of escape behavior in the
      crayfish.
AB  - Fifty years ago C.A.G. Wiersma established that the giant axons of the crayfish
      nerve cord drive tail-flip escape responses. The circuitry that includes these
      giant neurons has now become one of the best-understood neural circuits in the
      animal kingdom. Although it controls a specialized behavior of a relatively
      simple animal, this circuitry has provided insights that are of general
      neurobiological interest concerning matters as diverse as the identity of the
      neural substrates involved in making behavioral decisions, the cellular bases of
      learning, subcellular neuronal computation, voltage-gated electrical synaptic
      transmission and modification of neuromodulator actions that result from social
      experience. This work illustrates the value of studying a circuit of moderate,
      but tractable, complexity and known behavioral function.

PMID- 10203853
TI  - Calcium transients and neurotransmitter release at an identified synapse.
AB  - It is widely accepted that the modulation of the presynaptic Ca2+ influx is one
      of the main mechanisms by which neurotransmitter release can be controlled. The
      well-identified cholinergic synapse in the buccal ganglion of Aplysia has been
      used to study the modulations that affect presynaptic Ca2+ transients and to
      relate this to quantal evoked neurotransmitter release. Three types of Ca2+
      channel (L, N and P) are present in the presynaptic neurone at this synapse.
      Influxes of Ca2+ through N- and P-type channels trigger the release of ACh with
      only N-type Ca2+ channels being regulated by presynaptic neuromodulator
      receptors. In addition, presynaptic Ca2+ stores, via complex mechanisms of Ca2+
      uptake and Ca2+ release, control the Ca2+ concentration that triggers this evoked
      ACh release.

PMID- 10203854
TI  - The EGR family of transcription-regulatory factors: progress at the interface of
      molecular and systems neuroscience.
AB  - The EGR family of transcription regulatory factors, which is implicated in
      orchestrating the changes in gene expression that underlie neuronal plasticity,
      has attracted the attention of both molecular and systems neuroscientists. In
      this article, the advances made in both these fields of research are reviewed.
      Recent systems-based studies underscore the remarkable sensitivity and
      specificity of the induction of the expression of genes encoding EGR-family
      members in naturally occurring plasticity paradigms. However, they also challenge
      conventional views of the role of this family in plasticity. Recent molecular
      studies have identified the gonadotropin subunit, luteinizing hormone beta, as an
      EGR1-regulated gene in vivo and uncovered an essential role for EGR3 in muscle
      spindle development. In addition, the discovery of novel proteins that are
      capable of suppressing EGR-mediated transcription cast doubt over the prevalent
      assumption that changes in EGR mRNA or protein levels provide an accurate measure
      of EGR-driven transcriptional activity.

PMID- 10203855
TI  - Identifying genes for alcohol and drug sensitivity: recent progress and future
      directions.
AB  - New methods for identifying chromosomal regions containing genes that affect
      murine responses to alcohol and drugs have been used to identify many provisional
      quantitative trait loci (QTLs) since 1991. By 1998, 24 QTLs had been definitively
      mapped (P<5x10(-5)) to specific murine chromosomes, which indicates the presence
      of a relevant gene or genes at each location. The syntenic (homologous) region of
      the human genome for these genes is often known. For many mapped QTLs, candidate
      genes with relevant neurobiological function lie within the mapped region. Data
      that implicate candidate genes for specific responses include studies of knockout
      animals. Current strategies for gene identification include the use of congenic
      strains containing QTL regions introduced from another strain. There is
      increasing emphasis on gene-gene and gene-environment interactions in such
      studies.

PMID- 10203857
TI  - Folkerts and Nijkamp reply.
AB  - Airway epithelium: more than just a source for epithelium-derived relaxing
      factors!

PMID- 10203856
TI  - Why adult mammalian intrafusal and extrafusal fibers contain different myosin
      heavy-chain isoforms.
AB  - Multiple isoforms of the contractile protein myosin are present in mammalian
      skeletal muscles. The diversity of the heavy-chain subunits of myosin (MyHCs) in
      intrafusal fibers is thought to reflect a pathway of differentiation that is
      unique to muscle spindles. In fact, intrafusal MyHCs are developmental isoforms
      expressed by the prenatal precursors of both intrafusal and extrafusal fibers. In
      adult limbs, developmental MyHCs persist in intrafusal, but not extrafusal fibers
      principally due to the afferent neurons that arrest their maturational
      replacement by MyHCs associated with faster shortening velocities. The slow
      shortening velocities that are characteristic of developmental MyHCs might be
      adaptive for precise calibration of muscle spindles as sense organs.

PMID- 10203861
TI  - GABAB receptors make it to the top--as dimers.

PMID- 10203862
TI  - Advances in vascular neuroeffector mechanisms.

PMID- 10203863
TI  - Human adrenoceptor polymorphisms: evolving recognition of clinical importance.

PMID- 10203864
TI  - B1 receptors as a new inflammatory target. Could this B the 1?
AB  - The kinins, particularly bradykinin (BK), are important mediators involved in
      both the initiation and progression of an inflammatory response. The pro
      inflammatory effects of kinins are mediated by at least two receptors: the B2
      subtype is expressed constitutively and the B1 receptor is induced following
      tissue inflammation and damage. The endogenous ligand for the B1 receptor is des
      arg9BK, a cleavage product of the activity of carboxypeptidase on BK. Activation
      of B1 receptors produces a range of pro-inflammatory effects including oedema,
      pain and promotion of blood-borne leukocyte trafficking. In this article Amrita
      Ahluwalia and Mauro Perretti briefly describe the biology of BK and its
      receptors, and discuss the possible development of B1 receptor antagonists as
      novel anti-inflammatory agents.

PMID- 10203865
TI  - Emerging functions for neuropeptide Y5 receptors.
AB  - The Y5 subtype of neuropeptide Y (NPY) receptors has raised considerable interest
      as a mediator of NPY-stimulated food intake, but with the advent of recent data,
      this hypothesis has come into question. Moreover, Y5 receptor-selective drugs
      might not be specific for food intake because additional functions in the central
      and peripheral nervous systems, including endogenous anti-epileptic activity,
      attenuation of morphine withdrawal symptoms, enhancement of diuresis and
      natriuresis, lowering of blood glucose and reduction of acetylcholine release in
      the ileum, have recently been reported to occur via Y5-like receptors. Given that
      mRNA for the cloned Y5 receptor is apparently restricted to the CNS, Angela
      Bischoff and Martin Michel discuss the possible existence of additional NPY
      receptor subtypes with Y5-like recognition features and their presence in
      peripheral tissues.

PMID- 10203866
TI  - Neuroactive steroids: potential therapeutic use in neurological and psychiatric
      disorders.
AB  - Neuroactive steroids are a novel class of positive allosteric modulators of the
      GABAA receptor. Although neuroactive steroids are endogenous neuronal modulators,
      synthetic entities with improved oral bioavailability have recently been
      developed. These compounds demonstrate efficacy as anticonvulsants against a
      range of convulsant stimuli and demonstrate anti-epileptogenic activity in a
      kindling model of epilepsy. Efficacy has also been reported in preclinical models
      of anxiety, insomnia, migraine and drug dependence. Clinical evidence to date is
      generally supportive of these findings and indicates that neuroactive steroids
      are generally well tolerated. Taken as a whole, current data suggest that
      neuroactive steroids could have a future role in clinical practice. In this
      article, Maciej Gasior, Richard Carter and Jeffrey Witkin review preclinical and
      clinical evidence that forms the basis for predicting the potential therapeutic
      application of neuroactive steroids.

PMID- 10203867
TI  - Capsaicin, protons and heat: new excitement about nociceptors.
AB  - The past few years have witnessed a remarkable progress in understanding the
      neurobiology of pain. Important advances have been made particularly in the field
      of peripheral signal transduction in nociceptors. Membrane receptors have been
      identified for capsaicin, a pungent ingredient of chilli peppers, protons (i.e.
      acidic solutions) and for heat, three stimuli that specifically excite
      nociceptors. Of particular interest appears to be the first cloned capsaicin
      receptor, VR1, which has been suggested to serve as an integrator of these three
      nociceptive stimuli. These findings not only give new insights into the molecular
      machinery of nociceptor activation and sensitization, but can also provide a
      rational basis for pharmacological research aiming for a new class of
      peripherally acting analgesics, which should selectively interfere with
      nociceptor activation.

PMID- 10203868
TI  - Chimaeric G alpha proteins: their potential use in drug discovery.
AB  - Approaches that allow ligand occupancy of a wide range of G protein-coupled
      receptors to be converted into robust assays amenable to relatively high
      throughput analysis are ideal for screening for novel ligands at this class of
      receptor. Many attempts have been made to design universal ligand-screening
      systems such that any GPCR can be screened using a common assay end-point.
      Manipulation of the G protein within the assay system offers the possibility of
      achieving this. To better understand the domains involved in the interactions
      between G protein-coupled receptors, G proteins and effector polypeptides and the
      fine details of these contacts, a wide range of chimaeric G protein alpha
      subunits have been produced. Graeme Milligan and Stephen Rees discuss the
      information generated by such studies and the ways in which such chimaeric G
      proteins can be integrated into assay systems for drug discovery.

PMID- 10203871
TI  - The importance of the maternal lateral position.

PMID- 10203873
TI  - Diclofenac does not modify methadone bioavailability in cancer patients.

PMID- 10203874
TI  - Re: Temporary drainage of symptomatic malignant ascites by a catheter inserted
      under computerized tomography.

PMID- 10203875
TI  - A new palliative prognostic score: a first step for the staging of terminally ill
      cancer patients. Italian Multicenter and Study Group on Palliative Care.
AB  - In recent years, extensive research has been performed to identify prognostic
      factors that predict survival in terminally ill cancer patients. This study
      describes the construction of a simple prognostic score based on factors
      identified in a prospective multicenter study of 519 patients with a median
      survival of 32 days. An exponential multiple regression model was adopted to
      evaluate the joint effect of some clinico-biological variables on survival. From
      an initial model containing 36 variables, a final parsimonious model was obtained
      by means of a backward selection procedure. The Palliative Prognostic Score (PaP
      Score) is based on the final model and includes the following variables: Clinical
      Prediction of Survival (CPS), Karnofsky Performance Status (KPS), anorexia,
      dyspnea, total white blood count (WBC) and lymphocyte percentage. A numerical
      score was given to each variable, based on the relative weight of the independent
      prognostic significance shown by each single category in the multivariate
      analysis. The sum of the single scores gives the overall PaP Score for each
      patient and was used to subdivide the study population into three groups, each
      with a different probability of survival at 30 days: (1) group A: probability of
      survival at 30 days > 70%, with patient score < or = 5.5; (2) group B:
      probability of survival at 30 days 30-70%, with patient score 5.6-11.0; and (3)
      group C: probability of survival at 30 days < 30%, with patient score > 11.0.
      Using this method, 178/519 (34.3%) patients were classified in risk group A, 205
      (39.5%) patients were in risk group B, and 136 (26.2%) patients were in risk
      group C. The patients classified in the three risk groups had a very different
      survival experience (logrank = 294.8, P < 0.001), with a median survival of 64
      days for group A, 32 days for group B, and 11 days for group C. The PaP Score
      based on simple clinical and biohumoral variables proved to be statistically
      significant in a multivariate analysis. The score is valid in this population
      (training set). An independent validation on another patient series (testing set)
      is required and is the object of a companion paper.

PMID- 10203876
TI  - Successful validation of the palliative prognostic score in terminally ill cancer
      patients. Italian Multicenter Study Group on Palliative Care.
AB  - The aim of this work was to validate a previously constructed prognostic score
      for terminally ill cancer patients in order to determine its value in clinical
      practice. The Palliative Prognostic Score (PaP Score) was tested on a population
      of 451 evaluable patients consecutively entered in the hospice programs of 14
      Italian Palliative Care Centers. The score subdivided patients into three
      specific risk classes based on the following six predictive factors of death:
      dyspnea, anorexia, Karnofsky Performance Status (KPS), Clinical Prediction of
      Survival (CPS), total white blood count (WBC), and lymphocyte percentage. The
      performance of the PaP Score index in the training and testing sets was evaluated
      by comparing mortality rates in the 3 prognostic risk categories. The score was
      able to subdivide the validation-independent case series into three risk groups.
      Median survival was 76 days in group A (with a 86.6% probability of 30-day
      survival), 32 days in group B (with a 51.6% probability of 30-day survival), and
      14 days in group C (with a 16.9% probability of 30-day survival). Survival
      medians were remarkably similar to those of the training set (64 days in group A,
      32 days in group B, and 11 days in group C). In the complex process of staging
      terminally ill patients, the PaP Score is a simple instrument which permits a
      more accurate quantification of expected survival. It has been validated on an
      independent case series and is thus suitable for use in clinical practice.

PMID- 10203877
TI  - The symptom burden of seriously ill hospitalized patients. SUPPORT Investigators.
      Study to Understand Prognoses and Preferences for Outcome and Risks of Treatment.
AB  - We studied symptom burden and associated factors in a cohort of 1582 seriously
      ill patients admitted at five tertiary care academic centers in the U.S. between
      June 1989 and June 1991 in the SUPPORT Study. Logistic regression was used to
      test the independent association of symptoms with demographic, psychological,
      chronic, and acute illness measures. Pain, dyspnea, anxiety, and depression
      caused the greatest symptom burden. The following symptoms accounted for 67.3% of
      all symptoms that were at least moderately severe at least half of the time:
      dyspnea (19.2%), pain (17.6%), pain/dyspnea (7.6%), anxiety (5.9%), depression
      (5.0%), anxiety/depression (4.4%), anxiety/depression/pain/dyspnea (3.9%), and
      nausea (3.7%). Hospital, male gender, disease category, more comorbidities, more
      dependencies in activities of daily living prior to illness, and poorer quality
      of life were associated with greater symptom burden. Seriously ill patients have
      a high symptom burden. Better strategies will be needed to control symptoms in
      these patients.

PMID- 10203878
TI  - How effective are supplementary doses of opioids for dyspnea in terminally ill
      cancer patients? A randomized continuous sequential clinical trial.
AB  - Supplementary doses of opioids are recommended to relieve dyspnea in terminally
      ill cancer patients. We conducted a randomized continuous sequential clinical
      trial to evaluate their efficacy. We recruited 33 terminally ill cancer patients
      from three palliative care centers, all of whom had persistent dyspnea after rest
      and treatment with oxygen. Patients formed 15 successive pairs matched on route
      of administration. Within each pair, the order of allocation was randomly
      assigned, one patient receiving 25%, the other 50% of his 4-hourly opioid dose.
      Five measurements of dyspnea intensity and respiratory frequency were made during
      4 hours of follow-up. For each pair, a preference was attributed to the more
      effective regimen. The two regimens received an almost equal number of paired
      preferences (8 vs. 7). Overall, both mean dyspnea intensity and respiratory
      frequency decreased significantly relative to baseline. Dyspnea reduction was
      relatively greater in patients with initially low and moderate dyspnea intensity.
      In terminally ill cancer patients with persistent dyspnea, 25% of the equivalent
      4-hourly dose of opioid may be sufficient to reduce both dyspnea intensity and
      tachypnea for 4 hours.

PMID- 10203879
TI  - Cancer pain: knowledge and attitudes of physicians in Israel.
AB  - The effectiveness of cancer pain therapy is influenced by the attitudes and
      knowledge of the treating physicians. As part of a quality improvement project in
      the management of cancer pain, a survey of 236 medical practitioners was
      conducted. One hundred seventy-six respondents (74.5%) completed the survey.
      Fifty-two percent treated patients with cancer pain several times a week or more.
      Whereas 57.7% of physicians stated that 76-100% of patients could achieve a
      satisfactory outcome from analgesic therapy, only 17.2% of respondents reported
      that > 75% actually achieve a satisfactory outcome in their own experience.
      Unsatisfactory outcome was ascribed to inadequate pain relief (59.7%), or
      excessive central nervous system (CNS) side effects (43.3%). According to the
      responding physicians, the major barriers to effective relief include inadequate
      assessment of the pain and pain relief (65.3%), inadequate knowledge of pain
      therapy (57.9%), and physician reluctance to prescribe opioids (49.1%). Questions
      evaluating physician knowledge identified widely prevalent knowledge deficits in
      pain physiology, risk of addiction, use of adjuvant analgesics, opioid dosing,
      and treatment of side effects. Specialists in oncology tended to evaluate their
      knowledge more highly than others (P < 0.05). Despite this, there was no
      significant knowledge difference between oncologists and noncancer specialists.
      The data highlight some of the barriers to the successful management of cancer
      pain in Israel, the prevalence of knowledge deficits, and the common disparity
      between clinicians' self-assessment of clinical competence and their ability to
      respond correctly to questions on the management of cancer pain.

PMID- 10203880
TI  - Changing acute pain management to improve patient outcomes: an educational
      approach.
AB  - The United States Agency for Health Care Policy and Research (AHCPR) Acute Pain
      Management Guidelines were written to provide a scientific basis for practice.
      Educational programs designed to promote use of the guidelines may change
      practice in community hospitals. This article describes the development and
      implementation of an education program for nurses, physicians, and pharmacists in
      six community hospitals. Program content addressing the use of continuous quality
      improvement (CQI) teams, detailed pain histories, application of algorithms and
      dose calculation is described; direct and indirect outcome measures are reviewed.
      Six months after the program, all three experimental sites reported use of the
      AHCPR Guidelines in practice. Nurses reported that assessment and documentation
      of patients' duration of pain were perceived to be the most important caregiver
      behaviors providing benefit to patients: Across all respondents' reports of
      regularly performed activities, the activity performed by the largest proportion
      was assessing and documenting pain using a 0-10 rating scale.

PMID- 10203881
TI  - Treatment of painful skin ulcers with topical opioids.
AB  - Recent research suggests that opioid receptors on peripheral nerve terminals may
      play an important role in the modulation of pain. Clinical applications of this
      knowledge have been rather slow to evolve. We describe a consecutive series of
      nine patients with painful skin ulcers due to a variety of medical conditions.
      All patients were treated with a topical morphine-infused gel dressing. Seven of
      the nine patients experienced substantial and another experienced a lesser (but
      still significant) degree of analgesia. The ninth reported no relief, but his
      wound was not an open ulcer. Discussion centers on the practical application of
      this development in the large number of patients with painful skin lesions.

PMID- 10203882
TI  - Nebulized scopolamine in the management of oral dribbling: three case reports.
AB  - Difficulty swallowing saliva or its excessive production may be problematic for
      some patients. The resulting oral dribbling is often embarrassing. Three patients
      were admitted for hospice care complaining of oral dribbling. Each patient was
      given nebulized scopolamine hydrobromide which helped lessen the dribbling.

PMID- 10203883
TI  - Low-dose ketamine in the management of opioid nonresponsive terminal cancer pain.
AB  - Two patients with far-advanced cancer, near death, who were experiencing
      excruciating and intractable pain that was poorly responsive to rapidly
      escalating doses of morphine and hydromorphone were treated with low-dose
      intravenous ketamine (0.1-0.2 mg/kg). This intervention eliminated the need for
      any further opioid use, providing profound analgesia and a sense of calm during
      the last hours and days of these patients' lives. These case reports add to the
      small but growing body of clinical literature suggesting that ketamine may have a
      significant place in the care of patients with pain that is poorly responsive to
      opioids, or who experience dose-limiting adverse effects, near the end of life.
      This is an important matter to disseminate in order to reassure the public that
      we do have the tools necessary to keep the promise that no one need die with
      uncontrolled pain. This therapeutic approach may also serve to reassure concerned
      physicians that their efforts to assure pain relief may not be misconstrued as
      hastening death.

PMID- 10203884
TI  - Case presentation: pain, suffering and the unconscious patient.

PMID- 10203885
TI  - Commentary: who defines suffering?

PMID- 10203886
TI  - Commentary: neurobiology, suffering, and unconscious brain states.

PMID- 10203888
TI  - Old hat.

PMID- 10203887
TI  - A debt service.

PMID- 10203889
TI  - Flossing defended.

PMID- 10203891
TI  - TMD and the laws of physics.

PMID- 10203890
TI  - Words of caution.

PMID- 10203892
TI  - Straight-line access.

PMID- 10203893
TI  - Safety needles.

PMID- 10203894
TI  - Affluence and dental care.

PMID- 10203896
TI  - Contact points.

PMID- 10203897
TI  - Palatal deformations caused by pacifiers.

PMID- 10203895
TI  - Subsidized schools.

PMID- 10203898
TI  - Dental management service organizations. Lessons from medicine.
AB  - BACKGROUND: While management service organizations are new to dentistry, they
      have existed in medicine for many years. The author examined why they developed
      and what happened to three of them during 1998 to provide dentistry with insights
      into the future of dental management service organizations, or DMSOs. METHODS:
      The author identified and examined the three largest physician practice
      management firms, or PPMs, as of early 1998. He monitored their stock prices and
      fiscal changes through 1998. He also tracked all publicly traded DMSOs for growth
      and evaluated their stock price changes. RESULTS AND CONCLUSIONS: Economic
      pressures to control the cost of health care led to the development of
      organizational structures designed to increase the cost effectiveness of, and to
      control more variables associated with, health care delivery. The lure of
      vertical integration of health care delivery with the resultant control of
      multiple variables-including primary and specialty care, pharmaceuticals and
      hospitals-promoted the development of many PPMs and DMSOs, although many
      variables differ for dentistry. PRACTICE IMPLICATIONS: The realities associated
      with the loss of control in the corporate model, the lack of sufficient operating
      margins to support investor expectations and plummeting stock prices call into
      question the wisdom of universally embracing similar models for dentistry.

PMID- 10203899
TI  - Immediate complications of local anesthetic administered to 1,007 consecutive
      patients.
AB  - BACKGROUND: Probably the most common procedure in dentistry is the administration
      of local anesthetic, or LA. Immediate complications of LA administration include
      positive blood aspiration, blanching of the tissue and burning sensation on
      impingement of the nerve. Because studies about the immediate complications of LA
      administration were conducted before 1980, more recent data regarding this
      procedure are needed. MATERIALS AND METHODS: In this prospective study, an
      experienced dentist administered, 2,528 LA injections to 1,007 consecutive
      patients with 1-inch 27-gauge needles, using a solution of 2 percent lidocaine
      and 1:100,000 nordefrine hydrochloride. RESULTS: The authors observed positive
      blood aspiration in 73 injections (2.9 percent) without any further
      complications. The most severe immediate complication-syncope-occurred only in
      one case. In 63 injections (2.5 percent), the dentist touched the nerve, and the
      patient reported feeling an electric current sensation (40 times with inferior
      alveolar nerve blocks, 18 times with lingual nerve blocks, four times with mental
      nerve blocks and one time with a second injection to the same site) without any
      further complications. CONCLUSIONS: The results confirm that LA injections that
      are properly carried out appear to be safer today than they were in the past.
      CLINICAL IMPLICATIONS: LA is a safe procedure when the appropriate technique is
      used. It is even safer when an inferior alveolar nerve block is administered.

PMID- 10203900
TI  - Dental services: use, expenditures and sources of payment, 1987.
AB  - BACKGROUND: This article provides per capita estimates of dental care
      utilization, expenditures, mix of services and sources of payment for each of
      several socioeconomic and demographic categories. METHODS: The focus of the
      analyses presented here is on dental care utilization by the U.S. population
      during 1987. Specifically, national estimates are provided for dental visits,
      expenditures, sources of payment and procedure type for each of several
      socioeconomic and demographic categories using household data from the 1987
      National Medical Expenditure Survey, or NMES. RESULTS: During 1987, less that 50
      percent of Americans visited a dental office. Americans made approximately 292
      million dental visits and received approximately $30 billion worth of dental
      care, of which $10 billion was paid by insurers, $17 billion was paid out of
      pocket and $1.6 billion was not reimbursed. CONCLUSIONS: These analyses establish
      the magnitude of the dental care market and the amounts paid by individual
      patients, private insurance companies and Medicaid. They also reveal that the
      type of care received varies among people in distinct socioeconomic and
      demographic groups. PRACTICE IMPLICATIONS: Although the dental care market is
      substantial, many Americans do not visit a dentist. By understanding these
      analyses, practitioners will be better positioned to meet the dental needs of all
      Americans.

PMID- 10203901
TI  - Hepatitis viruses A, B, C, D, E and G: implications for dental personnel.
AB  - BACKGROUND: This article provides dental personnel with a brief overview of the
      different types of viral hepatitis, including their epidemiology, clinical
      features, prevention and treatment. It also explores the ramifications of these
      diseases for the practice of dentistry. DESCRIPTION OF THE CONDITION: Viral
      hepatitis is an inflammation of the liver caused by one of at least six distinct
      viruses. The hepatitis A and E viruses, or HAV and HEV, are enterically
      transmitted viruses that produce acute disease only. The hepatitis B, C and D
      viruses, or HBV, HCV and HDV, are most efficiently transmitted by infected blood,
      but also can be transmitted by exposure to other infectious bodily fluids. These
      three viruses can cause acute or chronic hepatitis. People with chronic viral
      hepatitis can develop chronic liver disease, cirrhosis and hepatocellular
      carcinoma. The hepatitis G virus was recently identified, and its ability to
      cause clinically significant acute or chronic hepatitis is unknown. CONCLUSIONS:
      Dental health care workers, or DHCWs, should be concerned primarily with HBV, HCV
      and HDV, as occupational exposure to these pathogens places them at risk of
      developing acute or chronic infections. Vaccines and immune globulins are
      available and effective in protecting against infections with HAV, HBV and HDV,
      but not HCV. CLINICAL IMPLICATIONS: DHCWs should become knowledgeable about viral
      hepatitis. They should be vaccinated against hepatitis B. Adherence to infection
      control measures will help prevent occupational transmission of all bloodborne
      pathogens, including hepatitis viruses.

PMID- 10203902
TI  - Evidence-based care in orthodontics and periodontics: a review of the literature.
AB  - BACKGROUND: In this article, the author reviews the evidence-based literature in
      the fields of periodontics and orthodontics to clarify the relationship between
      orthodontic tooth movement and various types of common periodontal disorders.
      TYPES OF STUDIES REVIEWED: The first section is a review of the literature on
      common periodontal disorders. The second is a review of evidence-based studies in
      the combined fields of orthodontics and periodontics, with a focus on orthodontic
      treatment possibilities, limitations and risks inherent in patients with
      periodontal disorders, particularly active periodontal disease. RESULTS: The
      literature on orthodontic tooth movement as it relates to periodontal disease
      shows that proper orthodontic treatment in patients with excellent oral hygiene
      and the absence of significant periodontal disorders should not pose any
      significant periodontal risk. In the presence of poor oral hygiene, however, and
      under circumstances of certain types of periodontal disorders, fixed orthodontic
      appliances and tooth movement can contribute to significant deleterious
      periodontal consequences. CLINICAL IMPLICATIONS: This review provides a clear
      understanding of what is known about orthodontic treatment possibilities,
      limitations and inherent risks in patients who may have certain types of
      periodontal disorders. It also underscores the importance of teamwork among the
      restorative dentist, periodontist and orthodontist when planning treatment for
      these patients. The author also offers a specific patient management protocol for
      this interdisciplinary dental team to follow.

PMID- 10203903
TI  - HIV-associated parotid lymphoepithelial cysts.
AB  - BACKGROUND: An outstanding feature of the diffuse infiltrative lymphocytosis
      syndrome, or DILS, a subset of HIV-1 disease, is asymptomatic bilateral parotid
      swelling. Recognition of the entity is important because people with this disease
      will seek routine dental care. CASE DESCRIPTION: The authors present a classic
      case of DILS. The patient exhibited bilateral parotid swellings caused by
      lymphoepithelial cysts, cervical lymphadenopathy, a CD8 circulating lymphocytosis
      and a CD8 lymphocytic infiltration into the labial salivary glands. A right
      superficial parotidectomy had been performed several years previously. However,
      no intervention was advised for the remaining left parotid because of its benign
      course. CLINICAL IMPLICATIONS: Since patients with DILS can develop lymphomas,
      periodic observation is mandatory. Any change in the growth pattern requires that
      a fine-needle aspiration biopsy be performed.

PMID- 10203904
TI  - Ask the expert. Anything new in pit and fissure sealants?

PMID- 10203905
TI  - Ask the expert. What intensity is best in light curing?

PMID- 10203906
TI  - Adverse drug interactions in dental practice: interactions associated with local
      anesthetics, sedatives and anxiolytics. Part IV of a series.
AB  - BACKGROUND: This article is the fourth in a five-part series based on a 1998
      International Association for Dental Research symposium entitled "Adverse Drug
      Interactions in Dentistry: Separating the Myths From the Facts." The symposium
      evaluated the significance of various drug interactions associated with dental
      therapeutics. METHODS: Local anesthesia and preoperative oral sedative/anxiolytic
      therapy often are indicated for routine oral surgery and restorative dentistry.
      The author conducted a literature review of the drug interactions associated with
      the use of local anesthetics and sedatives. The quality of the information used
      to document these interactions and the severity of the possible adverse outcome
      were assessed using a significance rating scale for dental drug interactions.
      RESULTS: Many of the frequently described drug interactions were found to be
      poorly documented in the dental and medical literature. Others were determined
      not to be relevant to current dental practice. The use of local anesthetics,
      sedatives or anxiolytic agents in combination with other central nervous system
      depressant agents or in combination with drugs that inhibit their metabolism was
      associated with a few serious adverse drug interactions or complications.
      CONCLUSIONS: The adverse drug interactions associated with the use of local
      anesthetics and oral sedative/anxiolytic agents in general practice vary in
      significance. An understanding of possible adverse drug interactions in dentistry
      may help practitioners avoid and prevent these complications.

PMID- 10203907
TI  - Intracoronal and extracoronal tooth restorations 1999.

PMID- 10203908
TI  - Toward a common theme for autoimmunity.

PMID- 10203909
TI  - Assessing the effectiveness of locally delivered chlorhexidine in the treatment
      of periodontitis.
AB  - BACKGROUND: Several multicenter random clinical trials have studied a second
      generation easy-to-use chlorhexidine local delivery system to assess its
      effectiveness as an adjunct to scaling and root planing, or SRP. METHODS: The
      author reviews the pharmacokinetics of the local delivery system and two of the
      multicenter randomized clinical trials. One study evaluated 118 patients using
      split-arch design and the other study 447 patients using parallel design. All
      patients underwent SRP. Test sites, which had pocket depths of 5 millimeters or
      larger, received a chlorhexidine chip (in both studies) or a placebo chip (the
      parallel study only). Test sites that remained 5 mm or larger were re-treated
      with a chip at three months and at six months (parallel study only). RESULTS:
      Both studies found greater mean reductions in probing depth when the
      chlorhexidine chip was used in conjunction with SRP than when SRP was used alone
      (1.16 mm vs. 0.7 mm, P < or = .0001, in the split-arch-design study and 0.95 mm
      vs. 0.65 mm, P = .00001, in the parallel-design study). The combined therapy
      resulted in significantly more sites with probing depth reductions of 2 mm or
      more compared with SRP alone (49.5 percent vs. 32.1 percent; P < .0001, in the
      split-arch-design study and 19.1 percent vs. 8 percent, P < .0001, in the
      parallel-design study). CONCLUSIONS: Use of the chlorhexidine chip has
      significantly improved the clinical parameters of periodontitis when used as an
      adjunct to SRP. CLINICAL IMPLICATIONS: When used with SRP, the chlorhexidine chip
      offers the clinician a new method of achieving and maintaining periodontal
      stability.

PMID- 10203910
TI  - Altered preparation design for cracked teeth.

PMID- 10203911
TI  - Dental care utilization: how saturated is the patient market?
AB  - BACKGROUND: Dental care utilization is the percentage of the population who
      access dental services over a specified period. In this article, the authors
      report on the results of several dental care utilization studies. METHODS: To
      date, dental utilization data have been gathered by large national studies via
      telephone interviews, face-to-face interviews or written surveys. In this
      article, the authors report on and compare dental care utilization rates provided
      by the Centers for Disease Control and Prevention, the National Center for Health
      Statistics, the Agency for Health Care Policy and Research and the American
      Dental Association. RESULTS: As captured by the various studies, the percentage
      of people who indicated they visited a dentist within the past year increased
      gradually between 1983 and 1997. The authors found that dental care utilization
      rates are higher among women than they are among men, and they decrease with age
      and increase with income and educational level. CONCLUSIONS: Although the
      available data vary, they suggest that more Americans are visiting a dentist. The
      demand for dental care is increasing overall, as well as across educational,
      racial and economic lines. PRACTICE IMPLICATIONS: If, as recent studies suggest,
      approximately 75 percent of the population visits a dentist annually, there is
      only modest room for further expansion of dental care utilization. However, if
      dental care utilization rates are substantially lower as reported in older
      studies, then there is a greater potential for increased dental care utilization.

PMID- 10203912
TI  - What level of scrutiny is required in an antitrust case? 2.

PMID- 10203913
TI  - Tribute to a coalition builder and distinguished public servant: Representative
      Louis Stokes.

PMID- 10203914
TI  - A new vision for the 21st century.

PMID- 10203915
TI  - Management of obesity in low-income African Americans.
AB  - The Bariatrics Clinic at Howard University Hospital was initiated to help low
      income African-American adults with low literacy skills in obesity control.
      Fourteen African-American women and two men participated in the study. Essential
      components of the treatment included nutrition education, exercise, and behavior
      modification related to food intake. The nutrition education component involved
      teaching nutritional needs, taking into account low literacy skills, low economic
      status, and individual food preferences. A realistic diet plan was based on
      individual needs, economic status, availability of food, likes and dislikes,
      lifestyle, and family dynamics. On average, patients lost 2 lb a week on this
      program. On average, a 14-lb weight loss occurred in seven weeks. There has been
      a 10% dropout from this program as opposed to drop out rates of 40% to 50% with
      other treatments. The main reasons for the success of this program is that it is
      individualized and is sensitive to food preferences.

PMID- 10203916
TI  - The influence of gender on incidence and outcome of patients with bladder cancer
      in Harlem.
AB  - Although African Americans have a lower incidence of bladder cancer, overall
      survival is worse compared with American whites. This phenomenon has been
      attributed to the higher incidence of advanced disease at diagnosis and poor
      follow-up. Fifty-nine cases of bladder cancer were identified through the Tumor
      Registry at Harlem Hospital and reviewed retrospectively. Complete data were
      obtained for 42 patients. The primary independent variables of interest were
      primary care utilization, comorbid conditions, social variables, and gender. The
      outcome variables of interest were stage of disease at presentation and death.
      The median age at diagnosis in this group was 73 years compared with 68 for
      bladder cancer patients in the United States. There was no statistically
      significant correlation between primary care utilization or severity of
      comorbidities, and clinical stage at presentation. Similarly, these variables did
      not influence the occurrence of death as an outcome. For women, the mean age at
      diagnosis was 74.2 years compared with 67.3 in men (P = .112). The ratio of male
      to-female cases in this group was 1.3 to 1 compared with 2.7 to 1 for the general
      US population. Women had lower odds of being diagnosed with superficial disease
      (OR = 0.24, 95% CI, 0.06-0.94) and a higher incidence of a cancer-specific death
      (OR = 2.7, 95% CI). The poor outcome and high incidence of bladder cancer cases
      among women in Harlem is intriguing. Overall, primary care utilization,
      comorbidities, and other social factors did not seem to influence stage or death
      as an outcome. The significantly elevated prevalence of smoking among women in
      this community, increased age at diagnosis, and possible environmental influences
      may play a role.

PMID- 10203917
TI  - Racial bias in federal nutrition policy, Part I: The public health implications
      of variations in lactase persistence.
AB  - The Dietary Guidelines for Americans from the basis for all federal nutrition
      programs and incorporate the Food Guide Pyramid, a tool to educate consumers on
      putting the Guidelines into practice. The Pyramid recommends two to three daily
      servings of dairy products. However, research has shown that lactase
      nonpersistence, the loss of enzymes that digest the milk sugar lactose, occurs in
      a majority of African-, Asian-, Hispanic-, and Native-American individuals.
      Whites are less likely to develop lactase nonpersistence and less likely to have
      symptoms when it does occur. Calcium is available in other foods that do not
      contain lactose. Osteoporosis is less common among African Americans and Mexican
      Americans than among whites, and there is little evidence that dairy products
      have an effect on osteoporosis among racial minorities. Evidence suggests that a
      modification of federal nutrition policies, making dairy-product use optional in
      light of other calcium sources, may be a helpful public health measure.

PMID- 10203918
TI  - Increased incidence of prostate cancer in Nigerians.
AB  - An increased incidence of prostate cancer among African-American men (now the
      second most common cause of cancer death) has been attributed mainly to the
      introduction of screening techniques, which have enabled earlier diagnosis of
      patients. This study reviewed male cancer patients recorded in a Nigerian cancer
      registry to assess the current trends in prostate cancer in Nigeria. For
      comparison, data were broken into two groups: 1980-1988 and 1989-1996. Only the
      top 10 cancers occurring in both periods were considered initially in this
      report. For emphasis, an analysis of adult male cancers was done per decade since
      1960. Results show that prostate cancer has become the number one cancer in
      Nigerian men and constitutes 11% of all male cancers. The median age of patients
      was 67.5 years (variance 5.6), and the mean age was 71.4 years (variance 14.3).
      These results indicate that despite the absence of screening programs in Nigeria,
      the number of prostate cancer cases has increased. The known risk factors
      probably contribute to a varying degree among Nigerians, who are generally of
      average build or in the low-normal range for body mass index. Moreover, the role
      of genetics cannot be underplayed. Given its biological characteristics, more
      cases of prostate cancer probably would be recorded among this population if
      screening were undertaken.

PMID- 10203919
TI  - Human immunodeficiency virus infection in Haiti.
AB  - This article reviews human immunodeficiency virus (HIV) infection in Haiti. The
      evolution of the epidemic in Haiti, its spread from urban to rural areas, its
      varied clinical manifestations, and the attitudes of Haitian people toward HIV
      infection provide important lessons on understanding and managing this infection
      in a developing country. The heterosexual spread of HIV, particularly among the
      poor, is well-documented as is the role of other sexually transmitted diseases
      along with tuberculosis. Coinfection of HIV and tuberculosis have led researchers
      to study the effects of six-month supervised intermittent tuberculosis therapy
      both in controlling tuberculosis and slowing the progression of HIV. Various
      surveys and discussion groups about acquired immunodeficiency virus knowledge and
      beliefs demonstrate a large deficit in HIV education despite campaigns to educate
      the population. The great impact of HIV disease on morbidity and mortality in
      Haiti indicates that a great deal of work still needs to be accomplished and
      demonstrates the frustration in fighting the infection in countries with
      inadequate resources and infrastructure. Advances in HIV vaccine research seem to
      be the most promising option for developing countries such as Haiti.

PMID- 10203920
TI  - Epithelioid leiomyoma of the vulva.
AB  - Smooth muscle tumors are uncommon lesions of the vulva and represent a variety of
      histologic types. When encountered, surgical treatment is guided by the malignant
      potential of the tumors. This article presents the case of a 45-year-old woman
      who underwent conservative excision of a 10-cm vulvar lesion consistent with
      benign epithelioid leiomyoma. This unusual case provides an opportunity to review
      the clinical and pathologic features of this uncommon variant of leiomyoma and to
      describe the recently suggested pathologic criteria for determining the malignant
      potential of smooth muscle tumors arising in the vulva. Knowledge of these
      criteria can guide the clinician in selecting the appropriate management.

PMID- 10203921
TI  - [Dependence and obsession].
AB  - Alcoholism, especially the urge to drink and relapse from abstinence, is deeply
      associated with obsession. And also alcoholics on abstinent 10 years or more are
      still higher on the obsessive-compulsive symptom dimension more than the
      depression and interpersonal sensitivity. Obsession was introduced by Kraepelin
      in 1915 and has been studied extensively since. When a person with obsession
      becomes exhausted with chronic rumination accompanied suspicion, he or she is
      driven to impulsive acts like alcoholics, and develops a personality disorder
      that displays persistent abnormal activities. Impulsive-compulsive spectrum
      characterizes by dimensions of risk-aversive/risk-seeking and harm-avoidant/harm-
      minimizing behaviors. Disorders on the compulsive end of the spectrum include
      obsessive-compulsive disorder, hypochondriasis, body dysmorphic disorder,
      anorexia nervosa an depersonalization. Mixed compulsive and impulsive disorders
      include Tourette's disorder, trichotillomania, pathologic gambling, sexual
      compulsions and alcoholism. Disorders on the impulsive end of the spectrum
      include borderline personality disorder and antisocial personality disorder.
      Using 123I-IMP SPECT, regional cerebral blood flow significantly decreased in
      alcoholics without Korsakoff sign (WAIS FIQ 90 or over) than alcoholics with
      Korsakoff signs (WAIS FIQ 89 or under) and control on the frontal lobe and
      thalamus. Recent model of obsessive-compulsive pathophysiology demonstrating that
      cortical regions have different effects on the direct and indirect pathways,
      indicates that the the different effects of serotonergic agents in the cortex
      alone could result in a change in balance between the direct versus indirect
      basal ganglia pathway. This article reviews alcoholism and obsession, ego
      dystonic and ego syntonic, approach-avoidance conflict, a recent biological
      approach to alcoholics and a spectrum for obsession.

PMID- 10203922
TI  - [Drinking alcohol among junior high school students: reflecting drinking
      culture].
AB  - Using a data obtained from a junior high school students survey on drug use,
      perception of alcohol drinking for junior high school students and role of adults
      in drinking were examined. 78% of the junior high school students had ever drunk
      alcohol at least once. The results revealed that experience of drinking alcohol
      accompanied by family did not have a close relationship with regularity of daily
      life routine, school lives and family lives for the students. It was, however,
      strongly suggested that experience of drinking alcohol only with peers had a
      close relationship with undesirable daily life routine, school lives and family
      lives for the students. Furthermore, lifetime prevalence of cigarette smoking and
      that of solvent inhalation for the male students with experience of drinking only
      with friends were 11 to 13 times and 5 to 8 times higher, respectively, than the
      male students without experience of drinking only with friends. These were 22
      times and 3 to 5 times, respectively, for female students. As for observance of
      the law which prohibits drinking alcohol for those under 20 years old, over a
      half of the students consider that alcohol drinking for minors was acceptable
      depending on the time and circumstances. This was greatly different from the
      observance of the laws against cigarette smoking and solvent inhalation. The
      author considers that this may reflect adult alcohol drinking culture in Japan.

PMID- 10203923
TI  - [Mechanism of inhibitory effects of ethanol on gallbladder contraction:
      differences in cases of histamine- and acetylcholine-induced contraction].
AB  - We investigated the effects of different concentrations of ethanol on contraction
      of gallbladder isolated from guinea pig. Ethanol at 25 mM significantly inhibited
      the contraction induced by histamine, but not those by KCl and acetylcholine. A
      higher concentration (100 mM) of ethanol inhibited both histamine-, acetylcholine
      and KCl- induced contractions. The inhibitory effect of the lower concentration
      (25 mM) of ethanol was not observed in the presence of verapamil, an antagonist
      of L-type Ca2+ channel or staurosporine, a selective inhibitor of protein kinase
      C. Verapamil and staurosporine significantly inhibited both histamine- and
      acetylcholine-induced contractile responses: the inhibitory effect was more
      potent for the histamine contraction. Our recent study has demonstrated that
      contraction caused by protein kinase C activation is completely dependent on Ca2+
      influx through the L-type Ca2+ channel in gallbladder smooth muscle of guinea
      pig. Therefore, the difference in 25 mM ethanol effect on histamine- and
      acetylcholine-induced contractions may be due to different degree of involvement
      of protein kinase C activation in the agonist-induced contraction. On the other
      hands, the higher concentration (100 mM) of ethanol inhibits the common pathway
      of contraction in gallbladder smooth muscle cells.

PMID- 10203924
TI  - [Relationship between identified patient (IP) with alcoholic problems and
      familial factors: in reference to family function, co-dependence, family group
      and self-help group participation].
AB  - In 1994, a survey was conducted to 105 wives of alcoholics (identified patient:
      IP) about levels of their family adaptability, cohesion, co-dependence, family
      group and self-help group participation. In 1995, a follow-up survey was
      conducted to the same wives. 87 wives responded to the follow-up questionnaire.
      17 responses were excluded due to too many missing responses. Statistical
      analyses were therefore conducted to the remaining 70 subjects. The following
      results were found. 1) Balanced as opposed to extreme levels of cohesion were
      associated with abstinence. 2) Family system changes on cohesion and/or
      adaptability dimensions were associated with abstinence. 3) Wife's over
      involvement with drinking husband somewhat appeared to be related to continuation
      of drinking. As for participation in family group or self-help groups, there was
      no significant difference between abstinence and drinking groups.

PMID- 10203925
TI  - Measuring medical students' reluctance to prescribe opioids for cancer pain.
AB  - Among 644 senior medical students a 14-item scale which was internally consistent
      indicated no change over the 6 years of testing in intent to reserve opioids for
      terminally ill.

PMID- 10203926
TI  - Influences of adult attachment in exploration.
AB  - Research into the relationship between attachment quality in both children and
      adults suggests links with patterns of exploration; however, exploration has been
      operationalized differently in studies of adults and children. This study
      examined adults' patterns of exploration operationalized in terms of novelty
      seeking, curiosity, and impulsivity, as in studies of children. Analysis
      indicated avoidant adults reported significantly lower curiosity than did
      securely attached adults, while preoccupied subjects showed no differences from
      either secure or avoidant groups. As in studies of children, groups did not
      differ on measures of novelty seeking or impulsivity.

PMID- 10203928
TI  - Black South African students' use of counseling service.
AB  - This paper reports the demographic and summative annual data for presenting
      concerns of students seeking counseling at a Black South African university.
      Rankings of the major presenting concerns identified by the clients are
      presented.

PMID- 10203927
TI  - Sex, competitiveness, and intimacy in same-sex friendship in Hong Kong
      adolescents.
AB  - One of the alleged reasons that males report lower intimacy in same-sex
      friendships than females is that males tend to be more competitive than females,
      but this assumption has not been empirically tested. In the current study, 121
      Hong Kong adolescents filled out Chinese versions of the Intimate Friendship
      Scale and the Competitiveness Index. As predicted, females reported having more
      intimate same-sex relationships than males, and they scored lower on
      competitiveness than males. However, the correlations between scores on the
      Competitiveness Index and the Intimate Friendship subscales were small and
      nonsignificant, suggesting that the sex difference in intimacy was not a function
      of competitiveness.

PMID- 10203929
TI  - Psychosocial development and moral development: an exploratory comparison of
      adolescents in Japan and America.
AB  - Building on previous cross-cultural research, this exploratory study examined the
      comparative psychosocial and sociomoral development of 46 adolescents--22
      Japanese in Japan, 10 Japanese in the United States, and 14 Euro-Americans in the
      United States. Euro-American participants obtained more positive scores than
      Japanese in the United States and Japanese in Japan on six psychosocial stages
      and the total psychosocial score as measured by the Measures of Psychosocial
      Development. Except in the Contract/Truth domain, all groups scored at a
      comparable level in sociomoral development as measured by the Sociomoral
      Reflection Measure-Short Form. Results are discussed in terms of cultural
      differences affecting adolescent development with implications for research and
      professional practice.

PMID- 10203930
TI  - Depression, self-defeating, and self-destructive behaviors as predictors of
      suicide ideation in males and females.
AB  - Previous studies have implicated depression, self-defeating behaviors, and self
      destructive behaviors in suicide ideation. The present research directly compared
      these three concepts as predictors of both males' (n = 51) and females' (n = 78)
      suicide ideation. Analysis confirmed sex differences, with depression and self
      defeating behaviors predicting females' suicide ideation, and self-destructive
      behaviors predicting males' suicide ideation. These results suggest that suicide
      may be related to these subtle yet relevant factors which may not be easily
      detected by mental health workers.

PMID- 10203931
TI  - On the puzzle of language, pragmatics, and schizophrenia.
AB  - The nature of circularity in thinking about language in schizophrenia is
      described, and initial observations by Byrne, et al. appropriate for breaking
      that circularity identified.

PMID- 10203932
TI  - Order and chaos in thoughts, feelings, and actions.
AB  - In the context of the concept of determinate chaos, introduced in psychology in
      the nineties, a modified stimulus-response formula is suggested which deals with
      the probabilistic predictions of responses of animate systems (brainless animate
      systems, animals, human persons) on stimuli. The suggested formula is used here
      in elaboration of a model describing the relationship among thoughts, feelings,
      and actions. In the framework of the model, a Darwin-like selection of behavioral
      and mental responses on stimuli is realized which is influenced by feelings.
      Transformations of human persons into mentally unhealthy states are discussed
      with the help of representations of the elaborated model. The model invites
      empirical test.

PMID- 10203933
TI  - Pathological gambling and obsessive-compulsive spectrum disorders.
AB  - To test the hypothesis that pathological gambling can be classified as an
      Obsessive-Compulsive Spectrum Disorder, the Padua Inventory was administered to
      40 diagnosed pathological gamblers and a control group of 40 normal subjects.
      Analysis showed that the pathological gamblers obtained a significantly higher
      mean total score on obsessionality than controls. Elevated scores on two factors
      reflecting impaired control of mental activities and loss of motor control
      contributed to the over-all difference. In the context of other research
      suggesting pathological gamblers would score high on psychometric measures of
      impulsivity, this study provides preliminary support for a Spectrum Disorder
      Model, suggesting that pathological gamblers are characterised by elevated scores
      on traits of 'impulsivity' and 'obsessionality.'

PMID- 10203934
TI  - Validity of the MMPI-2 and Beck Depression Inventory for making decisions of
      organ allocation in renal transplantation.
AB  - Psychosocial factors are presented which affect clinical decision-making
      regarding the allocation of renal organs. Patients were rated as being either
      High Risk or Low Risk transplant candidates. High Risk candidates were scored as
      being significantly different from the Low Risk candidates on many psychosocial
      variables. Interestingly, significant differences were not found between these
      two groups on either the MMPI-2 or the Beck Depression Inventory. The validity of
      using information from these inventories to allocate organs is discussed.

PMID- 10203935
TI  - Effects of cigarette smoking on lexical decision-making.
AB  - 10 habitual smokers, aged 19-25 yr., were randomly assigned to smoke either a
      very low nicotine "Placebo" cigarette (.05-mg nicotine delivery as estimated by
      the FTC method) or a Nicotine cigarette (.7-mg estimated nicotine delivery). Each
      participant was asked to abstain from smoking for 4 to 7 hr. prior to testing.
      After completing a presmoking test of lexical decision-making, participants
      smoked either a Nicotine or Placebo cigarette and were then retested for reaction
      times and accuracy on the lexical decision test. When presented the most
      difficult lexical decisions, participants responded significantly faster after
      smoking a Nicotine cigarette than they did before smoking; smoking a Placebo
      cigarette did not affect reaction times. Response accuracy was unaffected by
      smoking either kind of cigarette. These results suggest that smoking a nicotine
      cigarette may improve attention or memory retrieval after several hours of
      smoking abstinence.

PMID- 10203936
TI  - AIDS knowledge among black drug users: an issue of reliability.
AB  - This study examined the reliability of an inventory measuring AIDS-related
      knowledge among 553 black drug users. Data were collected from a socially high
      risk community in Birmingham, Alabama. The KR-20 reliability scores were computed
      from the inventory for each drug-use group. The KR-20 reliabilities ranged from
      .39 to .57. These findings may suggest that the inconsistent reports of the
      predictive power of AIDS knowledge among drug users reported in previous studies
      might be related to the low internal consistencies of the inventory.

PMID- 10203937
TI  - Change on psychological scales following Buddhist and Roman Catholic retreats.
AB  - Orthogonal contrasts of Adjective Checklist pretest-posttest change scores
      obtained from adolescents who attended three-day Buddhist or Roman Catholic
      retreats (n = 204) and no treatment control participants (n = 102) indicated
      those who attended had higher change scores and greater change occurred among
      those attending the Buddhist meditation retreat.

PMID- 10203938
TI  - Differences in self-reported health behaviors between public health professionals
      and support staff.
AB  - Differences in self-reported health behaviors between public health professionals
      and support staff were examined. 431 women working in nine county health
      departments in northern Illinois completed the Health-promoting Lifestyle
      Profile. The professionals reported a healthier lifestyle than the support staff.
      This result was significant after adjustment for age, race, educational
      attainment, and job tenure. The findings were discussed in the context of several
      theories of behavior and the Health Belief and Health Promotion Models.
      Suggestions for research are provided.

PMID- 10203939
TI  - Psychometric evaluation of the Menstrual Joy Questionnaire.
AB  - Analysis of 10 terms in the Menstrual Joy Questionnaire of Delaney, Lupton, and
      Toth indicated that the 34 undergraduate students did not agree on the
      definitions of scale items. The authors discuss the use of this questionnaire as
      a stimulus in experimental research and as a measure of positive perimenstrual
      experience.

PMID- 10203940
TI  - Alienation and irrational beliefs in a nonclinical university population.
AB  - A total of 126 college students, 53 men and 73 women, completed the Manifest
      Alienation Scale and the Irrational Beliefs Scale to assess alienation and
      irrationality. A linear relationship indicated students with elevated Alienation
      scores showed substantially higher irrationality than did students scoring lower.
      Analysis suggests that a positive linear effect for measured irrationality and
      reported Alienation characterizes students in a nonclinical population. The
      relationship between normal and pathological Alienation and irrational belief are
      addressed, and potential interventions in clinical situations are considered.

PMID- 10203941
TI  - Mothers' adjustment to the birth of a second child: a longitudinal study on use
      of verbal and nonverbal behaviors toward two children.
AB  - 4 mothers' skillful use of verbal and nonverbal behaviors to their first and
      second children was examined while each mother was playing with them for about
      one year after the birth of the second child. Analysis showed that maternal
      verbal interactions with the firstborn were frequently accompanied by nonverbal
      interactions toward the secondborn, especially during the first few months
      postpartum. The concurrent use of verbal and nonverbal behaviors with the two
      children may be a behavioral strategy for the mother to adjust to the birth of
      the second child.

PMID- 10203942
TI  - Chronic drinking, binge drinking, and drunk driving II.
AB  - Data from the Rhode Island Behavioral Risk Factor Survey on self-reported alcohol
      consumption and drunk driving were examined. Driving while intoxicated was
      significantly associated with both binge drinking and chronic drinking, but the
      measures of drinking were not significantly associated.

PMID- 10203943
TI  - Stigmatization of social and intimacy loneliness.
AB  - 82 female and 62 male college students judged the psychosocial functioning and
      acceptability of hypothetical peers that depicted 2 Levels of Loneliness (Lonely
      versus Nonlonely) x 2 Domains of Loneliness (Social versus Intimacy). Analysis
      indicated the students stigmatized both social and intimacy loneliness; they
      ascribed lower psychosocial functioning to and were less accepting of the lonely
      than nonlonely peer for both the social and intimacy domains of loneliness. The
      students, however, displayed greater differentiation in the ascription of
      psychosocial functioning between the lonely and nonlonely peers for the intimacy
      than the social domain of loneliness.

PMID- 10203944
TI  - Adult smoking in the home environment and children's IQ.
AB  - In a sample of 3- and 5-yr.-old children, smoking in the home was found to be
      significantly and inversely related to IQ. Children of normal birth weight and
      without neurological impairment had been enrolled in a longitudinal study of
      child development. Analyses were conducted with sex, ethnicity, socioeconomic
      status, educational stimulation in the home, day care, and mother's intelligence
      controlled. Significant results were obtained for scores on the Peabody Picture
      Vocabulary Test-Revised at age three years and on the major Stanford-Binet Fourth
      Edition scales at ages three and five years. All effects were for the mother, not
      the father, smoking in the home.

PMID- 10203945
TI  - Forced exercise blocks learned helplessness in the cockroach (Periplaneta
      americana).
AB  - For three consecutive days, two groups of adult female cockroaches (Periplaneta
      americana) (ns = 10) received inescapable shock. 24 hr. later one group was
      exposed to 10 min. of forced exercise on a treadmill while the other group
      received no exercise. Both groups were then run in a shuttlebox escape task. The
      cockroaches exposed to forced exercise did not become helpless in the shuttlebox
      escape task.

PMID- 10203946
TI  - Suicide among German federal and state police officers.
AB  - Most American studies report higher police officer suicide rates in comparison to
      age-matched populations. In the Federal Republic of Germany police organizations
      are comprised of Federal Customs, 16 state police, and 2 federal police
      organizations. A survey carried out in 1997 yielded higher suicide rates for
      police officers also in Germany in comparison to rates of the comparable age
      group (25 per 100,000 vs 20 per 100,000). The most commonly used suicide method
      was firearms (66-71%). Hypotheses often attribute this high suicidality among
      police officers to higher work stress than in other professions. Other hypotheses
      implicate individual variables such as psychiatric illnesses, alcoholism, and
      interpersonal and marital problems. A transactional model might explain these
      different views.

PMID- 10203947
TI  - Individual differences in text comprehension as a function of test anxiety and
      prior knowledge.
AB  - This study investigated the relationship between reading comprehension and
      comprehension monitoring with undergraduates (223 women, 69 men). Further, the
      effect of test anxiety and of prior knowledge on reading comprehension and on
      comprehension monitoring was examined in groups of students of equal intellectual
      ability. Students with high scores on reading comprehension performed better on a
      comprehension monitoring task as well. Individual differences in reading
      comprehension with a multiple-choice response format emerged as a function of the
      interaction between test anxiety and prior knowledge. Students with low prior
      knowledge and high test anxiety performed worst of all. We found a far less
      detrimental effect of test anxiety and prior knowledge on monitoring
      comprehension than on reading comprehension.

PMID- 10203948
TI  - Defense mechanisms in alexithymia.
AB  - The Polish version of the Toronto Alexithymia Scale-20 and Defense Mechanisms
      Questionnaire were completed by 387 university students. Scores on alexithymia
      correlate significantly with scores on the whole group of 12 immature defenses
      (Pearson r = .39, p < .001) and with scores on such individual immature defense
      mechanisms as Autistic Fantasy (r = .39), Somatization (r = .37), Projection (r =
      .32), and Displacement (r = .32). These results support other findings indicating
      that alexithymia is significantly associated with immature ego defenses.

PMID- 10203949
TI  - French adaptation of the shortened version of the Profile of Mood States.
AB  - The French adaptation and validation of the short version of the Profile of Mood
      States is examined. A sample of 110 women diagnosed with breast cancer and 50 men
      with prostate cancer were administered the French Canadian adaptation of the
      shortened version of the profile (37 items). Means, test-retest correlations, and
      internal consistency coefficients (alpha) replicated the English initial
      validation. These results support the reliability of the French Canadian version.
      In addition, significant decrease from initial to retest testing for Anxiety,
      Depression, and Confusion subscales also supported construct validity.

PMID- 10203950
TI  - Lifeguards' vigilance: effects of child-adult ratio and lifeguard positioning on
      scanning by lifeguards.
AB  - Observers recorded visual scanning by four lifeguards at three indoor public
      swimming pools. Scanning increased as a positive function of the ratio of
      children to adult swimmers, i.e., scanning was greater when the ratio was high,
      suggesting that lifeguards became more concerned about the risks to children and
      the ability of nearby adult swimmers to monitor these children when the number of
      children significantly exceeded the number of adults. Absolute numbers of
      children, however, decreased number of scans, possibly because of greater number
      of incidents and rule violations requiring lifeguards' attention which competed
      with watching the pool. Lifeguards were more likely to scan a pool area when they
      were in elevated towers versus standing on the pool decks. Lifeguards' scanning
      declined later in the day, possibly due to fatigue or because of competing
      activities of pool maintenance.

PMID- 10203951
TI  - An assessment of the effectiveness of an intergenerational program for youth.
AB  - The purpose of this research was to assess the effectiveness of an
      intergenerational program for youth. Findings indicated that, after participating
      in the program, youth had more favorable attitudes toward the elderly and more
      knowledge of the aging process than youth in the control group. The program did
      not appear to have a direct effect on participants' willingness to volunteer,
      although results indicated that willingness to volunteer may increase indirectly
      through the improved attitudes of participants toward the elderly.

PMID- 10203952
TI  - Hope, goal-blocking thoughts, and test-related anxieties.
AB  - Based on Onwuegbuzie's 1998 findings pertaining to the relationship of lower
      scores on hope to higher ones on anxiety about statistics, a brief overview of
      the etiology of test-related anxieties in the context of Snyder's hope theory is
      given, and the utility of hope theory for helping students with test-related
      anxieties is explored.

PMID- 10203953
TI  - Intelligence test scores from infancy to adulthood for a craniopagus twin pair
      neurosurgically separated at 4 months of age.
AB  - Long-term effects in a neurosurgically separated twin pair were illuminated by
      standard psychological test scores obtained over a period from 2 to 38 years of
      age. Interdigitation of the gyri of their right frontal lobes had necessitated
      separation in two stages at 4 months of age. One twin clearly suffered some brain
      injury and showed some impairment during the testing at 5 years of age. The
      scores of both twins rose at the adult testing. The brighter twin has an IQ
      comparable to that of the mother. The unique data set is a kind of model for long
      term assessment of early brain surgery, particularly with craniopagus twins.

PMID- 10203954
TI  - Use in 1992 of tranquilizers and smokeless tobacco among Miami's public school
      students.
AB  - This analysis examined tranquilizer use by 466 adolescents in Dade County,
      Florida public schools in 1992. Significant factors which increased the
      probability of use include that the adolescents were female, older students,
      peers' use of tranquilizers, ready access, and they lived alone. Smokeless
      tobacco use among 468 students was positively and significantly linked to peer
      influence, students being male, younger, living alone, and the availability of
      smokeless tobacco.

PMID- 10203955
TI  - Change in role perception, role conflict, and psychological health of working
      mothers.
AB  - A model of the interrelationship among Change in Role Perception, Role Conflict,
      and Psychological Health of working mothers is introduced. The model posits that
      Change in Role Perception after the birth of children influences Psychological
      Health directly or indirectly through Role Conflict. The model was tested with a
      sample of 192 employed mothers (aged 26-45 years) with at least one child under
      11 years of age and who lived in either Melbourne or Canberra, Australia. As
      expected, scores on Role Conflict predicted all four measures of Psychological
      Health (Anxiety, Self-esteem, Uptight, and Worn Out). Change in scores on Role
      Perception predicted Self-esteem and Worn Out. Geographic location predicted
      scores for Uptight and Worn Out and Occupational Type predicted scores for Worn
      Out, perhaps due to perceived social support. There are theoretical reasons for
      maintaining the model's structure. Refinement of methodology, measurement of
      Change in Role Perception, and possible adoption of a longitudinal approach is
      recommended. It is concluded that measuring experienced role conflict and change
      in role perception should be taken into account in any consideration of women's
      psychological health.

PMID- 10203956
TI  - Birth order and two marketing-related measures of aggression.
AB  - Several bodies of research link birth order and aggression. With a sample of 144
      women and 225 men business students, the present study investigated birth order
      and aggression using two measures from academic marketing. Neither measure
      detected significant influence of birth order. Implications are discussed
      regarding marketing and consumers' behavior.

PMID- 10203957
TI  - Progressive catatonia.
AB  - We present the case of a young man with a diagnosis of a childhood-onset
      pervasive developmental disorder who developed a progressive neurologic
      deterioration with persistent catatonia and right hemiparesis. On his initial
      evaluation approximately three years after the onset of mutism, he manifested
      right hemiparesis and catalepsy. Two years later, although catalepsy had
      subsided, motor function had deteriorated so that he could not use his hands to
      feed or dress himself. Oral-facialbuccal dyskinesia manifested by blepharospasm
      and grimacing were present constantly during waking hours. Quantitative
      electroencephalography demonstrated markedly decreased amplitude, a finding
      associated with catatonia. Left sural nerve biopsy indicated large axon cylinder
      degeneration. Left deltoid biopsy demonstrated perimysial fibrosis and type II
      fiber predominance. Although magnetic resonance imaging of the head without
      contrast was normal, positron emission tomography indicated hypometabolism of the
      right cerebral and the right cerebellar hemispheres. The patient continues to
      deteriorate despite a course of 25 electroconvulsive treatments. He continues to
      manifest criteria for catatonia including motoric immobility, mutism, and
      peculiarities of voluntary movement such as prominent grimacing. We suspect an
      inherited neurodegenerative disorder. Since catatonia is a treatable condition
      frequently associated with medical and neurological diseases, examination for the
      features of catatonia must be included in the assessment of patients with
      progressive brain degeneration. This report is an attempt to clarify the traits
      of a serious variant of progressive brain degeneration.

PMID- 10203958
TI  - Health-related correlates of gambling on the British National Lottery.
AB  - The National Lottery has been estimated as being played by 65% of the adult
      British population. This study investigated whether higher average weekly
      spending on the Lottery is associated with various health-related variables.
      Results from a survey of 482 British adults (mean age = 33.3 yr.), consisting of
      107 students and 375 people in employment, indicated that those who spent more on
      the Lottery had significantly poorer social functioning (Social Functioning scale
      of the SF-36 Health Survey), higher weekly alcohol and cigarette consumption, and
      lower frequency of social support (Emotional and Social Interaction scales of the
      Medical Outcomes Study Social Support Survey). By contrast, higher lottery
      spending was not associated with poorer general mental health (General Health
      Questionnaire). Manual workers spent over twice the weekly amount on the Lottery
      compared to nonmanual workers. Consumption of alcohol and cigarettes was lower
      than recently published UK norms. Results suggest that higher Lottery spending
      among the general adult population possibly may be linked specifically to
      restrictions in social activity. The association of Lottery spending with alcohol
      and cigarette use among a sample whose consumption was relatively low appears to
      require explanation within psychological theories of addiction. The over-all
      pattern of results is discussed in relation both to addiction theory and to the
      Lottery's widespread appeal and availability.

PMID- 10203959
TI  - The Holden Psychological Screening Inventory and sexual efficacy in urological
      patients with erectile dysfunction.
AB  - This paper examined the relationship between psychological adjustment and sexual
      ability in a sample of 33 men with erectile dysfunction and their spouses.
      Indices of sexual efficacy converged and were negatively associated with self
      reported depression. Data are interpreted as confirming the association between
      erectile dysfunction and psychological disturbance and as providing evidence of
      validity for the Holden Psychological Screening Inventory Depression Scale and
      the Sexual Self-efficacy Scale.

PMID- 10203960
TI  - Perceptions of quality of journals related to health education.
AB  - Faculty and chairpersons (N = 102) at 34 programs granting doctoral degrees in
      health education were asked to rate the quality of professional journals related
      to health education. The American Journal of Public Health was the highest rated
      journal. Health Education Quarterly was second, and Health Education Research,
      the only other health education journal, was rated in the top 10 (rated 7). The
      journals from the epidemiology area rated higher than journals from other areas.
      The respondents were least familiar with journals on the environment, safety, and
      death education.

PMID- 10203961
TI  - Perceived risk of work-related injury and intentions to change employment.
AB  - A survey of 263 employed men and women examined the effect of length of
      employment, perceived ability to find a better job, positive job features (pay,
      job security, and intrinsic interest), and perceived risk of occupational injury
      on intentions to stay with or leave one's current employer. Perceived risk of
      occupational injury significantly predicted one's belief that the person would
      not stay with the current employer. Perceived inability to find alternative
      employment lessened the desirability of leaving the current employer. Desire to
      leave was lower when a job was rated highly for pay, security, and intrinsic
      interest. Length of employment, as a measure of job commitment, was not a factor.

PMID- 10203962
TI  - Replication and extension analyzing the factor structure of Locus of Control
      scales for substance-abusing behaviors.
AB  - Two research questions were addressed in this study. First, what are the
      dimensions of the concept of control orientation with respect to substance
      abusing behaviors as measured by Keyson and Janda's 1972 Drinking-related Locus
      of Control Scale and by an adaptation of that scale developed for users of other
      drugs. Second, utilizing a large sample of both male and female clients who
      abused both alcohol and other drugs, how does that dimensional structure differ
      from the one presented by Donovan and O'Leary in 1978 for male alcoholics at a VA
      hospital. Since the present sample was a large (N = 542) representative sample of
      publicly subsidized clients in Missouri, it provided an opportunity to extend
      earlier work across type of drug abused and sex. Like Donovan and O'Leary we used
      a principal components analysis with a varimax rotation to examine the dimensions
      of the 25-item locus of control scales. Like those authors, the analysis for male
      alcohol users produced a three-factor solution with interpretations resembling
      their "intrapersonal" and "interpersonal" factors but with a more fully developed
      third factor interpretable as a fate or luck dimension. These dimensions were
      apparent for the other groups as well, although the first two factors were
      reversed for male users of other drugs and the analysis for female alcohol
      abusers showed a more consistent sociability dimension than for males. While the
      derived structures are therefore similar to Donovan and O'Leary's results and
      consistent with the theoretical uses of control orientation in discussion of
      alcohol and other drug abuse, they also show some differences for type of drug
      abused and by sex. These are necessary but not sufficient conditions for
      including such measures in more specific models relating clients' motivation and
      propensity for change to outcomes.

PMID- 10203963
TI  - Profile validity standards for MMPI and MMPI-2 F scales.
AB  - Although numerous indices of validity have been developed for the MMPI and MMPI
      2, interest in the F scale and its variants continues, especially among
      practicing clinicians. The use of the binomial for assessing standards for random
      answering and possibly for judgments of malingering offers another approach for
      the interpretation of F-scale scores. The theoretical binomial distribution and
      Monte Carlo data are in accord. Cut-off scores of 24 for the MMPI and 23 for the
      MMPI-2 suggest random responses, and scores of 40 and 37, respectively, suggest
      clinical interpretation rather than randomness of responding.

PMID- 10203964
TI  - Suicide among eminent artists.
AB  - To evaluate suicide risk by profession among eminent artists data from Garzanti's
      Encyclopedia, a broad biographical repertory, were used. Six categories in the
      visual and literary arts were compared: architects, painters, sculptors, writers,
      poets, and playwrights. Only people whose deaths occurred in the 1800s or 1900s
      were included since it is likely that underestimation of suicide has been lower
      in the more recent centuries. A total of 59 suicides were observed in a sample of
      3,093 people: this corresponds to a ratio of 1.90%. Suicides were 51 among men
      (ratio 1.75%) and 8 among women (ratio 4.30%). The comparison by profession
      indicates that poets and writers exceed the mean suicide ratio of the sample.
      Painters and architects, conversely, have a clearly lower risk than the mean.
      Mean age of suicides was 44 yr. (SD = 12), with writers being slightly older (48
      yr., SD = 12) than other artists. Artists who died of causes other than suicide
      reach a mean of 65 yr. (SD = 10). Suicide among artists seems to have a peculiar
      pattern, clearly different from the pattern of the general population, wherein
      suicide risk is higher among men and older people. Adverse financial
      circumstances and the stress attributed to rejection of personal products may
      contribute to the specific risk of suicide among artists. The link between mental
      disorders, such as manic-depression, which imply a higher risk of suicide, and
      creativeness is discussed as a contributing factor.

PMID- 10203965
TI  - Factors influencing placement recommendations for hospitalized individuals with
      chronic mental illness.
AB  - This study was undertaken to identify factors that may preclude a patient's
      discharge from a community mental health center and result in the patient being
      labeled "unplaceable." Placement recommendations differed between the state
      hospital staff and a mental health professional employed by the center to
      evaluate 28 patients. A measure designed to assist in the assessment of patients'
      competencies suggested the professionals' recommendations were more related to
      patients' skills in areas associated with community living than were those of the
      state hospital staff. Follow-up indicated that 15 patients discharged according
      to the professionals' recommendations maintained community tenure. Use of a more
      psychometrically sound and comprehensive assessment concerning discharge and
      placement may improve likelihood of success.

PMID- 10203966
TI  - Temperament and loving-styles in college women: associations with eating
      attitudes.
AB  - The purpose of the present study was to examine the associations of temperament
      and love attitudes with eating behaviors in 190 college-aged nonclinical women
      who completed a survey that included measures of temperament, loving-style, and
      eating attitudes. Certain temperament and loving-style variables showed
      significant statistical association with scores on eating attitudes.
      Specifically, both obsessive and game-playing love-styles were related to the
      Dieting and Bulimia-Food Preoccupation dimensions of the eating scales, while
      temperamental fear and anger were related to bulimia and oral control. The role
      of interpersonal relationships and self-perceptions of temperament may provide a
      useful perspective for understanding the etiology of eating disorders.

PMID- 10203967
TI  - Sex education sources and attitudes about premarital sex of Seventh Day Adventist
      youth.
AB  - 37 Seventh Day Adventist youth were surveyed about their sex education and
      attitudes towards premarital sex. Analysis indicated differences between their
      attitudes and actual sexual behaviour. While 70% endorsed the church's
      prohibition on premarital sex, 54% had engaged in premarital sex.

PMID- 10203968
TI  - Effect of restriction of working memory on reported paranormal belief.
AB  - 56 college students completed Tobacyk's 1988 Revised Paranormal Belief Scale and
      Watson, Clark, and Tellegen's 1988 Positive and Negative Affect Scale.
      Experimental group participants, but not control group participants, rehearsed a
      five-digit number while completing the Paranormal Belief Scale. Analysis showed
      higher reported paranormal belief for experimental group participants but no
      differences on the Positive and Negative Affect Scale. Results are discussed in
      terms of the effect of restriction in working memory on the critical evaluation
      of paranormal phenomena.

PMID- 10203969
TI  - Executive functioning and compliance in HIV patients.
AB  - 25 adult HIV patients were evaluated in a study of appointments, medication, and
      compliance with restrictions on sexual activity. The Executive Interview (EXIT)
      was useful in assessing these patients for cognitive difficulties; compliance
      with medication and countertransference issues were negatively correlated with
      EXIT scores.

PMID- 10203970
TI  - Assessment of memory functioning among an aging sample.
AB  - To provide additional basic normative data and an enhanced understanding of
      memory functioning of older individuals, 100 subjects equally divided into 5-yr.
      age intervals from 60 to beyond 80, evenly split by sex and socioeconomic status,
      and balanced for racial composition were tested on 19 memory measures commonly
      used in clinical and neuropsychological assessment. While analyses indicated that
      10 measures were significantly related to age, performance was quite stable from
      60-74 years, dropping primarily at the oldest age intervals. No significant age
      related differences were found on the remaining 9 measures, and in all instances
      considerable variability was evident. The study provides evidence against
      stereotypes that our population as a whole shows a generalized or severe memory
      decline with advancing age. Clearly, no one should hastily assume limitations in
      memory which would routinely disqualify older individuals in work, independent
      living, and decision-making. Recommendations are made for practicing clinicians
      who must choose instruments appropriate for normal and abnormal subjects.

PMID- 10203971
TI  - [Slowly progressive dressing and constructional apraxia: symptomatological study,
      especially for dressing apraxia].
AB  - In 1982, Mesulam drew attention to a clinical picture characterized by slowly
      progressive aphasia without dementia, and since then, there have been many such
      reports. Recently, there have been 30 reports of slowly progressive apraxia.
      However, the nature of this apraxia is not uniform. We now report a patient with
      slowly progressive dressing and constructional apraxia. The patient is a 60-year
      old right-handed woman with a 2-year history of a slowly progressive praxic
      disturbance. On admission, she was alert and aware of this difficulty. A
      neurological examination disclosed mild rigidity and myoclonus in her left hand.
      A neuropsychological assessment disclosed severe dressing apraxia, which was
      unlikely to be caused by dementia and moderate constructional apraxia. Her
      dressing apraxia was manifested in upper limbs, neck, trunk and lower limbs.
      However, she could express verbally the action of dressing. She also showed mild
      limb-kinetic apraxia, but neither ideational apraxia nor ideomotor apraxia was
      present. Aphasia and agnosia were also absent. On an MRI, the bilateral cerebral
      hemispheres were atrophic (right > left). A 99m-Tc ECD SPECT revealed decreased
      uptake in the right cerebral hemisphere and left frontal lobe, and an EEG showed
      slow waves over the right cerebral hemisphere. There have been 30 reports of
      slowly progressive apraxia. Most of these cases presented with slowly progressive
      clumsiness in one or both hands as an initial symptom, followed by
      constructional, ideomotor or dressing apraxia. Our patient differed from these
      cases in that dressing and constructional apraxia progressed slowly without any
      other apraxia except only mild limb-kinetic apraxia. There was a similarity
      between dressing apraxia of our patient and that of Marie's and Brain's original
      cases.

PMID- 10203973
TI  - [A case of Foix-Chavany-Marie syndrome and crossed aphasia after right corona
      radiata infarction with history of left hemispheric infarction].
AB  - Foix-Chavany-Marie syndrome (FCMS) is a syndrome that presents facio-pharyngo
      glosso-masticatory diplegia with automatic voluntary dissociation. Its most
      common etiology is stroke in the regions of bilateral opercula. We described a 75
      year-old woman with FCMS and crossed aphasia. She had cerebral infarction of left
      middle cerebral artery territory 23 years before. At that time she had transient
      right hemiparesis, but no aphasia. This time, she suddenly became mute and was
      brought to our hospital. Neurological examination revealed severe weakness in her
      bilateral lower face, pharynx, tongue, and sternocleidomastoideus. She had no
      weakness of limbs. Her listening comprehension was moderately disturbed and
      handwriting was paragraphic. Her emotional facial movement was maintained despite
      of disturbed volitional facial movement. CT scan disclosed fresh infarction at
      the right corona radiata and old infarction at the left middle cerebral artery
      territory. In this patient, lesions at the left operculum and right corona
      radiata with the preserved right operculum gave rise to FCMS. This implies
      following possibilities: 1) the corticobulbar tract and corticospinal tract run
      separately at the corona radiata, 2) volitional and emotional tracts of facial
      movement run separately at the corona radiata. It was demonstrated that FCMS is
      not always caused by bilateral operculum lesions. Our patient did not show
      aphasia after the first stroke including left language area, but became severely
      aphasic after the right corona radiata infarction. Simultaneous occurrence of
      FCMS and aphasia after corona radiata lesion suggested that the corticobulbar
      tract and a tract that conducts linguistic information are running adjacently in
      the corona radiata. Our case suggested that restricted corona radiata lesion may
      cause severe subcortical aphasia and in case of additional contralateral
      corticobulbar tract lesion, severe dysarthria may occur.

PMID- 10203972
TI  - [Clinico-pathological analysis of vesiculotubular myopathy of adult onset].
AB  - The patient was a 50-year-old house wife. There were complicated consanguineous
      marriages in the family tree. Since 30 years of age, she had suffered from
      progressive limb muscle weakness, but without myalgia and myasthenia. At present,
      she was wheelchair-bound. Physical examinations showed obesity, congenital livedo
      racemosa, epicanthus palpebrae and left renal defect. Neurologically, facial,
      anterior cervical, and iliopsoas muscles were well preserved, but others were
      severely involved. Laboratory examinations revealed mildly elevated myogenic
      serum enzymes, and myogenic changes on needle EMG. In her muscle biopsy from the
      left rectus femoris muscle, there were no inflammatory changes, but marked
      variations of the fiber size as well as adipose tissue replacement were
      recognized. Strickingly, basophilic masses located in the center of the
      sarcoplasm were present in about 10% of the fibers. Histochemically, the masses
      were present in both type 1 and 2 fibers, and exhibited almost similar stained
      patterns to the tubular aggregates, but were dystrophin-, GRP78- and clathrin
      positive. Under electron microscopy, the masses consisted of aggregates of the
      vesiculotubular structure, measuring approximately from 60 nm to more than 6
      microns in diameter, which were continuous with T system/sarcoplasmic reticulum
      and were clearly segregated from myofilaments. This is a chronic progressive
      muscular disorder of adult onset with the peculiar pathological finding of
      vesiculotubular structure.

PMID- 10203974
TI  - [A case of McLeod syndrome].
AB  - A 52-year-old man was admitted to our hospital in 1997 because of high serum
      creatine kinase (CK) level. Neurologic findings revealed chorea on the trunk and
      extremities, mild weakness of proximal muscles, and absence of deep tendon
      reflexes in four extremities. Serum CK was elevated to 3,494 U/l (normal, below
      235). A peripheral blood smear showed acanthocytes in approximately 1% of the red
      blood cells (RBCs). Very weak expression of the Kell antigens (K2, K4, K5, and
      K7) on his RBCs led us to make a final diagnosis of McLeod syndrome. Muscle
      biopsy from the left biceps showed increased variability in fiber diameter, a few
      regenerating fibers, scattered fibers with internal nuclei, and mild fiber type
      grouping. Immunohistochemical analyses of dystrophin. merosin, and adhalin were
      normal. Although McLeod syndrome is a rare X-linked recessive disorder, it is
      clinically important for differential diagnosis of chorea acanthocytosis and
      hyperCKemia.

PMID- 10203975
TI  - [Gerstmann-Straussler-Scheinker syndrome with a Pro102Leu mutation in the prion
      protein gene and atypical MRI findings, hyperthermia, tachycardia, and
      hyperhidrosis].
AB  - A 64-year-old Japanese woman with Gerstmann-Straussler-Scheinker syndrome (GSS)
      is reported. She was admitted to our hospital for progressive amnesia, twitching
      of the right upper limb, and difficulty in speaking and walking for 5 months.
      Physical examination revealed a fever, tachycardia, and hyperhidrosis without any
      evidence of inflammation or infection. Neurological examinations demonstrated
      dementia, frontal lobe signs, and spontaneous myoclonus. She developed akinetic
      mutism 4 months later. The levels of neuron-specific enolase and 14-3-3 protein
      were elevated in the cerebrospinal fluid, and serial EEG showed periodic
      synchronous discharges. DNA analysis of the prion protein gene revealed a
      Pro102Leu mutation and therefore she was diagnosed as GSS102. Head MRI showed
      abnormal high signal intensity by T2 weighted image in bilateral caudate nuclei,
      putamen, frontal lobes, and white matter around the posterior horn of lateral
      ventricles at admission, and extension to global cerebral cortex and diffuse deep
      white matter with marked atrophy of bilateral frontal and cerebellar cortices 4
      months later. In 123I-IMP SPECT study, uptake of RI decreased slightly only in
      left frontal region at admission, but decreased markedly in bilateral frontal
      region 4 months later. Analysis of autonomic function (analysis of noradrenarine
      in plasma and urine, coefficient of variation of R-R intervals before and after
      giving atenolol, Aschner's eyeball pressure test, intracutaneous atropine and
      adrenaline injection test) revealed sympathetic hyperactivity but normal
      parasympathetic activity. This is a very rare case of GSS102 with atypical MRI
      findings and clinical features like Creutzfeldt-Jakob disease rather than GSS102,
      presenting hyperthermia, tachycardia, and hyperhidrosis caused presumably by
      sympathetic hyperactivity as well as fatal familial insomnia. Therefore it is
      suggested that some factors besides the codon mutation in the prion protein gene
      may influence clinical symptoms in prion disease.

PMID- 10203976
TI  - [A case of mononeuropathy multiplex associated with anti-GM1 and -SGLPG
      antibodies in a patient with ongoing Hashimoto disease].
AB  - We reported a case of mononeuropathy multiplex associated with anti-GM1 and 
      SGLPG antibodies in a patient with ongoing Hashimoto disease. A 56-year-old woman
      was admitted with asymmetrical patchy sensory and motor disturbance in the
      extremities. Muscle atrophy and weakness in the left palm and bilateral tibialis
      anterior muscles were also noted. Deep tendon reflexes were normal in all the
      extremities. Superficial and deep sensations were reduced in the hands and feet
      bilaterally, and the distribution of sensory loss was irregular. Her serum was
      positive for antinuclear antibody, rheumatoid factor, anti-RNP antibody, and anti
      SS-A antibody. Serial electrophysiological studies suggested that the predominant
      process was axonal degeneration of the sensorimotor nerves. On sural nerve
      biopsy, there were no findings of vasculitis but severe axonal degeneration was
      observed. Thin-layer chromatography with immunostaining revealed anti-GM1 and 
      SGLPG antibodies. Treatment with corticosteroids was successful. In this case,
      the anti-GM1 antibody may have played a role in the pathogenesis of
      mononeuropathy multiplex associated with autoimmune disease.

PMID- 10203977
TI  - [Brain infarct due to non-bacterial thrombotic valvular vegetation associated
      with primary antiphospholipid antibodies--a case report].
AB  - A 50-year-old woman with antiphospholipid antibody syndrome (APAS) awoke in a
      morning to notice dizziness, so she came to our hospital. Several hours later she
      developed left oculomotor paralysis. Further two hours later she developed right
      oculomotor paralysis and could not stand. Brain MRI showed high signal intensity
      lesion of paramedian thalamic and midbrain on the T2-weighted image. Cerebral
      angiography did not reveal any occlusion. Transesophageal echocardiography
      disclosed mitral valvular vegetation. We thought this valvular abnormality was
      non-bacterial thrombotic vegetation associated with APAS and this suggests that
      cerebral infarction was due to emboli from this vegetation.

PMID- 10203978
TI  - [A case of stiff-man syndrome with an antineuronal autoantibody against an 80 kDa
      protein].
AB  - A 23-year-old Japanese man had noted intermittent muscle stiffness in his lower
      limbs and trunk in addition to painful muscle cramps in his back over one year.
      The muscle stiffness continued and eventually spread to his upper limbs.
      Neurological examinations revealed saccadic ocular movement and stiffness in the
      masseter, neck and four limbs and truncal muscles, enhanced by both voluntary and
      passive movements. Although the mobility of his joints was severely limited, the
      muscle strength was preserved. Electromyograms showed the continuous firing of
      normal motor units at rest, which disappeared both during sleep and after the
      intravenous administration of 10 mg of diazepam. An oral glucose tolerance test
      showed a normal pattern. Both the adrenal and thyroid functions were normal. No
      antibody against glutamic acid decarboxylase was detected in either the patient's
      serum or cerebrospinal fluid (CSF). The serum antibody against the voltage-gated
      potassium channel was also negative. Western blot analysis revealed the presence
      of an antibody in his serum and CSF which reacted with an 80kDa protein in the
      rat cerebrum, cerebellum and human spinal cord, but not in the rat liver. This
      patient was thus diagnosed as having stiff-man syndrome. Treatment with oral
      diazepam (50 mg/day), a GABAA agonist, proved to be effective, whereas baclofen
      (75 mg/day), a GABAB agonist, was not. These results suggest the dysfunction of
      the GABA neurons in this case, similar to that as previously observed in other
      cases of stiff-man syndrome while, in addition, the function of the GABAB
      receptor was also markedly disturbed in this case.

PMID- 10203979
TI  - [A case of subacute necrotizing lymphadenitis complicated with brachial plexus
      neuritis].
AB  - A 22-year-old female noted a low grade fever and swelling of the cervical lymph
      nodes in May 1997, and later developed a dry cough. She was diagnosed to have
      interstitial pneumonitis, and then administration of corticosteroids alleviated
      her symptoms. On February 6, 1998, however, a high fever recurred and her swollen
      cervical lymph node on the right side was biopsied on February 9, 1998. A
      histological examination revealed an increased number of histiocytes and
      karyorrhexis of the lymphocytes in the paracortical areas, and she was therefore
      diagnosed to have histiocytic necrotizing lymphadenitis. She could not fully
      elevate her arm on February 16, 1998. On admission, her cervical lymph node was
      swollen on the left side. A neurological examination revealed a marked weakness
      of the right deltoid muscle, moderate weakness of the right latissimus dorsi,
      triceps and brachioradialis muscles and also a mild weakness of the serratus
      anterior, supra- and infra-spinatus, and biceps brachii muscles. The muscle power
      of the other muscles were normal and no muscle atrophy was evident. Winging of
      the right scapula was observed. The deep tendon reflexes were normal in all four
      limbs, and her sensation was also normal. No cerebellar sign was found. The
      Jackson, Spurling, Allen, Morley and Adson tests were all negative. ESR was
      mildly elevated to 18 mm/hr, but CRP was negative. RF, ANA and anti-SS-A and SS-B
      antibodies were positive, whereas LE-test, direct and indirect Coombs tests and
      other autoantibodies were negative. Needle EMG disclosed fasciculation potentials
      in the right triceps muscle and polyphasic waves in the right deltoid muscle. MRI
      showed gadolinium-enhancement of the right brachial plexus. Although an abnormal
      accumulation of gallium was detected in the right parotid and bilateral
      submandibular glands, no sicca symptoms were found and the Schirmer test findings
      were normal. Oral prednisolone (50 mg/day with gradual tapering) alleviated both
      her symptoms and the gadolinium-enhancement of the right brachial plexus. As a
      result, her right upper limb paresis was thus considered to have been caused by
      right brachial plexus neuritis, which was probably associated with histocytic
      necrotizing lymphadentis. Although acute cerebellar ataxia and meningitis have
      previously been reported to be complicated with histiocytic necrotizing
      lymphadenitis, this is the first report to describe the complication of
      peripheral neuritis with this condition.

PMID- 10203980
TI  - [Decreased blink frequency in myotonic dystrophy].
AB  - We counted spontaneous eye blink rate in 11 myotonic dystrophy (MD) patients.
      Seven healthy subjects as well as 10 Parkinson disease (PD) and 7 facio-scapulo
      humeral dystrophy (FSH) patients were used as controls. Blink frequency was
      significantly decreased in MD and PD patients (7.6 +/- 4.9/min in average and
      11.0 +/- 7.5/min, respectively), compared with healthy subjects and FSH patients
      (17.5 +/- 4.3/min and 17.3 +/- 9.9/min, respectively). Normal blink frequency in
      FSH suggests that the facial muscle weakness is not responsible for decreased
      blink frequency in MD. This observation is compatible with prolonged R1 latency
      in blink reflex in MD, suggesting a dysfunction of central mechanism of blink
      control system as in the case of PD, although there remains a possibility that
      the myotonia in levator palpebrae muscles disturbs blinking.

PMID- 10203981
TI  - [A case of spinal segmental myoclonus and propriospinal myoclonus: a
      neuroelectrophysiologic analysis].
AB  - A 37-year-old male patient with spinal segmental myoclonus and propriospinal
      myoclonus was described. He was admitted to our hospital because of paroxysmal
      axial myoclonus, which first appeared one month before. He denied any significant
      accident such as trauma or fever. Apart from myoclonus, no abnormal findings were
      observed by physical and neurological examinations, routine laboratory
      investigations and MRI of the cervical and thoracic spinal cords. The myoclonus
      consisted of continuous rhythmic contractions of the bilateral thoracal and
      abdominal muscles. Its frequency was approximately 0.3Hz. The clinical findings
      were typical of spinal segmental myoclonus. In addition, the myoclonus started in
      the thoracal muscles and frequently spread up to the neck muscles and down to the
      leg muscles. The myoclonus disappeared in sleep. Polymyography revealed the
      following findings: (1) The jerks were found on the bilateral axial muscles
      including sternocleidomastoid, biceps, triceps, pectoralis major, abdominal
      muscles and quadriceps. (2) Homologous muscles were activated synchronously. (3)
      The duration of bursts was variable ranging 100 to 400msec. (4) The jerks in the
      pectoralis muscle preceded those in other muscles. The latencies of the jerks in
      the other muscles increased with their distance from pectoralis, based on the
      linear regression analysis of the onset of jerks in the various muscles. (5) The
      jerks were induced by tapping or electrical stimulation anywhere on the body
      including the face, but not by flash or sound. From the above polymyographical
      findings, the myoclonus seems to originate in the T3 spinal cord and slowly up
      and down the spinal cord at 0.6-1.6 m/sec, suggesting that it is mediated by the
      propriospinal tract.

PMID- 10203983
TI  - [Neuroleptic malignant syndrome in a patient with polyneuropathy: mechanism of
      muscle rigidity and elevated serum creatine kinase levels].
AB  - A 49-year-old man was admitted with the chief complaints of muscle weakness and
      gait disturbance. His neurological examination was compatible with peripheral
      neuropathy, and laboratory tests revealed IgA monoclonal gammopathy, increased
      protein content in the cerebrospinal fluid (CSF) without pleocytosis, and slow
      motor and sensory nerve conduction velocity. He was diagnosed as having chronic
      inflammatory demyelinating polyneuropathy with IgA monoclonal gammopathy of
      undetermined significance. The patient was treated with steroid, and
      plasmapheresis. He became so restless that antidepressant and haloperidol were
      administered. Then, he became unresponsive, and developed high fever, sweating,
      tachycardia, and tremor. Examination of CSF showed increased 3-methoxy-4-hydroxy
      phenylglycol and decreased homovanillic acid. He was diagnosed as having
      neuroleptic malignant syndrome (NMS). However, his muscle tonus was still flaccid
      in his lower extremities that had been suffered from chronic polyneuropathy.
      Interestingly, his serum creatine kinase (CK) content was only slightly elevated.
      We suppose that the pathophysiological location of NMS might be primarily
      central, and that muscle rigidity and elevation of serum CK might not occur, if
      the peripheral nerves were completely impaired.

PMID- 10203982
TI  - [The number of plasma exchanges in Guillain-Barre syndrome: evaluation by the
      removal rate of immunoglobulin G].
AB  - The optimal number of plasma exchanges in Guillain-Barre syndrome had not been
      established. Recently, a clinical trial by the French Cooperative Group showed
      that 2 exchanges were sufficient for mild case of Guillain-Barre syndrome, but
      all others 4 exchanges were optimal. The supplementary examination is needed to
      validate the conclusion, but a certain period should be taken. As the second best
      way to determine the appropriate number of plasma exchanges, we simply examined
      the reduction rate of IgG on each session. Wilcoxon signed-ranks test showed that
      removal rates of IgG differed between the first and second sessions, and between
      the second and third sessions. At least, 2 exchanges seemed to be needed for
      Guillain-Barre syndrome. Our results confirmed that IgG is the most relevant
      factor in the pathogenesis of the syndrome.

PMID- 10203984
TI  - [Acute compression neuropathy of the proximal sciatic nerve in a patient with
      facioscapulohumeral muscular dystrophy].
AB  - We reported a 58-year-old man with facioscapulohumeral muscular dystrophy who had
      acute compression neuropathy of the sciatic nerve after prolonged sitting
      position. MRI and percutaneous electric stimulation studies were usefull for the
      diagnosis. Gd-DTPA T1-weighted MRI images showed the enhanced right sciatic nerve
      at the level of gluteus maximus muscle. An evoked potential study by a
      percutaneous electric stimulation revealed evidence of a conduction block at the
      same level. After methylprednisolone pulse therapy, muscle weakness and sensory
      disturbance improved. Acute compression neuropathy of the sciatic nerve may be
      seen as a complication in the advanced stage of (FSH) muscular dystrophy.

PMID- 10203985
TI  - [Structural biology of cell adhesion molecule cadherins].

PMID- 10203986
TI  - [Structure and function of helical cytokines and their cognate receptors].

PMID- 10203987
TI  - [Structural biology of the immune response on cell surface].

PMID- 10203988
TI  - [Structural biology of growth factors and growth factor receptors].

PMID- 10203989
TI  - [Structural view of mechanism of photo-signal transduction related with rhodopsin
      and heterotrimeric G protein].

PMID- 10203990
TI  - [Structural biology of SH2 and SH3].

PMID- 10203991
TI  - [Structural biology for PH and other domains involved in signal transduction].

PMID- 10203992
TI  - [Structural biology of small G proteins].

PMID- 10203993
TI  - [Structural biology of apoptosis proteins: recent advances in structural analysis
      of TNF-related, Fas-related, Bcl-2 family and caspase family proteins].

PMID- 10203994
TI  - [Structural biology of protein kinase C].

PMID- 10203995
TI  - [His-Asp phosphotransfer signal transduction].

PMID- 10203996
TI  - [Structural biology of Escherichia coli RNA polymerase].

PMID- 10203997
TI  - [Structural basis for chromatin transcription].

PMID- 10203998
TI  - [Function and structural biology of general transcription factors and RNA
      polymerase II in eukaryotes].

PMID- 10203999
TI  - [Structural biology of transcription factors and coactivators].

PMID- 10204000
TI  - [Molecular structures in DNA replication].

PMID- 10204001
TI  - [Structure and function of DNA repair factors].

PMID- 10204003
TI  - [RNA recognition by RNA-binding protein].

PMID- 10204002
TI  - [Structural biology of RecA and RuvABC proteins involved in homologous DNA
      recombination].

PMID- 10204004
TI  - [mRNA CAP binding protein].

PMID- 10204005
TI  - [Cytochrome c oxidase].

PMID- 10204006
TI  - [ATP synthase].

PMID- 10204007
TI  - [Membrane protein: bacteriorhodopsin].

PMID- 10204009
TI  - [Synchrotron radiation and biological crystallography].

PMID- 10204008
TI  - [Structures and functions of ion channels and pumps].

PMID- 10204010
TI  - [New aspects is stable-isotope-assisted NMR techniques: application to be
      structural analysis of larger complexes between proteins and nucleic acids].

PMID- 10204011
TI  - [Solid-state nuclear magnetic resonance].

PMID- 10204012
TI  - [Structural genomics: approach of structure biology towards genome analysis].

PMID- 10204013
TI  - [Large-scale protein preparation using the cell-free synthesis].

PMID- 10204014
TI  - [Chemical synthesis of phosphopeptides].

PMID- 10204015
TI  - [Aim of structural biology (discussion)].

PMID- 10204016
TI  - [Phagocyte-dependent free oxygen radical mechanisms of autoaggression in
      pathogenesis of internal diseases].

PMID- 10204017
TI  - [Active oxygen metabolites in provision and control of natural cytotoxic
      reactions].
AB  - Whether the redox active compounds that are able to generate and capture free
      oxygen radicals utilized in natural cytotoxicity (NCT) are involved in the
      provision and control of NCT in the body of man and animals is discussed.
      Evidence is given for the participation of endogenous metal-binding
      peptido(proteo)glycans (MBPPG) in the establishment and maintenance of regulatory
      balance in the complex of NCT reactions. Cyanobacterial exometabolites and their
      related metal-binding amphipathic compounds yielded in the exosystem was
      substantiated to be involved in the rational limitation of lymphocytic
      cytotoxicity. The findings suggest that exogenous redox active microbial products
      exert their action on NCT cells by changing the rate of generation and capture of
      free oxygen radicals by exogenous MBPPG.

PMID- 10204018
TI  - [Serum antioxidative activity].
AB  - Model systems used in the determination of serum antioxidative activity (AOA),
      which differ both in the way of generating free radicals and in the mode of their
      detection, are clinically analyzed. The specific features and potentialities of
      the model systems developed at the authors' laboratory are characterized. These
      included yolk lipoprotein suspensions, liposomal suspensions formed from total
      phospholipid fraction, the hemoglobin-hydrogen peroxide-luminol system. The
      investigations show that most model systems for determining serum AOA contribute
      to the water soluble interceptors of free radicals (ascorbate, urate, plasma
      proteins, etc.), chelating and oxidative agents of catalytically active Fe2+
      (ceruloplasmin, transferrin, albumin, etc.). The serum AOA levels measured with
      different model systems vary with the body's status. To determine serum AOA and
      the contribution of major endogenous antioxidants and inhibitors of free radical
      reactions may be a basis for the goal-oriented use of exogenous antioxidants in
      the therapy of a great variety of diseases.

PMID- 10204019
TI  - [Physicochemical aspects of cataract genesis].
AB  - Based on their own studies and the data available in the literature, the authors
      consider the physicochemical aspects of cataract genesis. Emphasis is laid on the
      role of oxidative stress in this diseases. It is suggested that one of the key
      mechanisms of cataract genesis is the exhausted lenticular potential and
      oxidative stress, resulting in the formation of products that enhance lenticular
      photo lesion and imbalance of cyclonucleotide- and Ca(2+)-dependent cascade
      systems of regulation, which leas to impaired cAMP-dependent protein
      phosphorylation. Decreased phosphorylation of lenticular fiber proteins reduces
      their solubility and results in their sorption on the cell membranes, resulting
      in progressive impairment of the regulatory membrane placement. Light scattering
      on the folded membrane surfaces in the lenticular fibers is considered to be a
      main cause of lenticular opacity in cataract.

PMID- 10204020
TI  - [Free radical mechanisms of low-intensive laser radiation].
AB  - A hypothesis of free radical mechanisms of stimulating action of low-intensive
      laser radiation (LILR) used for therapy of a variety of inflammatory diseases is
      formulated. The main points of the above hypothesis are as follows. Endogenous
      porphins are a LILR chromofor in the red band (lambda = 632.8 nm). Light
      absorption induces the production of initiating radicals that are involved in
      subsequent free radical reactions, in lipid peroxidation in particular. Modified
      lipid peroxidation in the cell membranes causes an increase in ion permeability,
      including that for Ca2+. The higher levels of Ca2+ in the leukocytic cytosol
      result in Ca(2+)-dependent cellular priming, which appeared as the increased cell
      functional potential and which is seen in subsequent leukocytic stimulation of
      the greater production of prooxidants and other biologically active products.
      These products include nitric oxide and a number of cytokines involved in the
      regulation of microcirculation. The paper presents experimental findings that can
      be regarded as evidence for some points of the above hypothesis which are used to
      provide a chain of events underlying the free radical mechanisms of stimulating
      action of low-intensive laser radiation.

PMID- 10204021
TI  - [Photo oxidative reactions of psoralens and their role in therapy of dermatoses].
AB  - Psoralenes (furocoumarins) in combination with ultraviolet (UV) A radiation (320
      400 nm) are used in the treatment of vitiligo, psoriasis, cutaneous T-cell
      lymphoma and other skin and autoimmune diseases (PUFA therapy). The mechanism of
      psoralene-photosensitive modification of biologically significant molecules, such
      as DNA, protein unsaturated lipids, antioxidants, etc. is considered in the
      paper. Particular emphasis is laid on the mechanism and biomedical significance
      of photo reactions proceeding via the stage of formation of psoralene photo
      oxidation products (POP). POP causes oxidative damage to many molecules in in
      vitro experiments and mediates the T-cell immunity cell in vivo, as appeared as
      suppression of delayed hypersensitivity and contact sensitivity in mice. The use
      of randomized double blind control has indicated that POP has therapeutical
      effects on eczema. A new modality of psoralene photo chemotherapy that consists
      in the UV-A radiation of psoralene solution followed by its administration (POP
      therapy) to patients. Unlike conventional PUFA therapy, POP therapy does not
      require the patients' skin to be exposed to UF-A radiation, which allows adverse
      effects, such erythema, skin hyperpigmentation, etc. to be avoided.

PMID- 10204022
TI  - [Molecular genetic aspects of neoplasms].
AB  - The paper presents data on the role of some genes that provide normal positive
      and negative regulation of cell proliferation. It considers their structural and
      functional changes that lead to the occurrence and progression of tumors. The
      characteristics of tumor suppressive genes whose inactivation determines
      hereditary predisposition to some forms of malignant neoplasms.

PMID- 10204023
TI  - [New evidence for cardiac biomechanics].
AB  - Acute and chronic experiments have indicated that myocardial layers contract
      asynchronically. The subendocardial and subepicardial are the first to contract.
      Their contractions change the shape of a ventricle (from ellipsoid to spherical),
      shorten the inflow pathway, displace stroke volume to the arterial cone, and
      expand the circular layer. The circular layers begins contracting 20-49 msec
      later. Its contraction is accompanied by a rapid rise of intraventricular
      pressure, elongation of the outflow pathway, an increase in cardiac length, and a
      slight stretching of the subendocardial and subepicardial layers. Simultaneous
      contraction of all three layers develops to reach T wave. At this point the phase
      of the maximum ejection ends. During the phases of reduced ejection, isovolumic
      decline of intraventricular pressure and rapid filling, the subendocardial layers
      and papillary muscles continue to contract whereas the relaxed circular layer
      extends. As a result, intraventricular pressure decreases, the ellipsoidal shape
      of ventricular changes to the circular one, the cups of the mitral and tricuspid
      valves open, and the sucking action of the ventricles develops. In other words,
      diastolic phases are active through the contraction of the subendocardial and
      subepicardial layers rather than through active relaxation. ECG shows U-wave at
      this moment.

PMID- 10204024
TI  - [Immuno-microbiological aspects of chronic bacterial prostatitis pathogenesis].
AB  - The paper deals with a role of the factors of the body's antiinfective resistance
      system in the pathogenesis of chronic bacterial prostatitis and with the
      identification of an etiological factor of the disease. Long-term studies have
      revealed that chronic bacterial prostatitis runs in the presence of impairments
      in the antiinfective resistance system, in failures of T lymphocytes, phagocytic
      activity, and opsonization in particular. Gram-positive cocci, predominantly
      Staphylococcus and Enterococcus alone or as part of 2-component associations have
      been found to be the leading agents in the etiology of chronic bacterial
      prostatitis.

PMID- 10204025
TI  - [Urokinase as a blood and urine plasminogen activator in chronic
      glomerulonephritis and amyloidosis].
AB  - To estimate the individual role of the plasminogen activators (PA) urokinase (u
      PA) and tissue (t-PA) in the development of two renal diseases (the nephrotic
      forms of chronic glomerulonephritis (CGN) and amyloidosis, the baseline plasma
      and urine levels of u-PA and t-PA antigens, their functional activity (FPAA), and
      changes in these parameters were determined after protein loading test (0.7
      g/kg). In healthy individuals and patients with amyloidosis, the baseline FPAA
      changes from 0 to the maximum were caused only by the alterations of u-PA levels,
      in those with CGN, they were induced by the changes in the content of u-PA and t
      AP antigens. The functional loading test revealed PA reserves solely in patients
      having a high baseline FPAA for both nephropathies: u-PA in amyloidosis and t-PA
      in CGN. In all the patients, the urine levels of u-PA antigens were 20-40 times
      more than those of t-PA antigens and 5-6 times less than those plasma u-PA. The
      findings suggest that urokinase may be regarded as the major plasminogen
      activator involved in CGN and amyloidosis.

PMID- 10204026
TI  - [Present-day global public health].

PMID- 10204027
TI  - [Immunobiotechnology on the way to 21st century].

PMID- 10204028
TI  - From flow injection to bead injection.

PMID- 10204029
TI  - Polarization sensing with visual detection.
AB  - We describe a new approach to fluorescence sensing which relies on visual
      determination the polarization. The sensing device consists of a fluorescent
      probe, which changes intensity in responses to the analyte, and an oriented
      fluorescent film, which is not affected by the analyte. An emission filter is
      selected to observe the emission from both the film and the sensing fluorophore.
      Changes in the probe intensity result in changes in the polarization of the
      combined emission from the sensor and reference. The degree of polarization can
      be detected visually using a dual polarizer with adjacent sections oriented
      orthogonally to each other. The emission passing through the dual polarizer is
      viewed with a second analyzing polarizer. This analyzer is rotated manually to
      yield equal intensities from both sides of the dual polarizer. This approach was
      used to measure the concentration of RhB in intralipid and to measure pH using 6
      carboxyfluorescein. The analyzer angle is typically accurate to 1 degree,
      providing pH values accurate to +/- 0.1 pH unit at the midpoint of the titration
      curve. We also describe a method of visual polarization sensing that does not
      require an oriented film and that can use the same fluorophore for the sample and
      reference. These approaches to visual sensing are generic and can be applied to a
      wide variety of analytes for which fluorescent probes are available. Importantly,
      the devices are simple, with the only electronic component being the light
      source.

PMID- 10204030
TI  - Amino acid order in polymeric dipeptide surfactants: effect on physical
      properties and enantioselectivity.
AB  - The effect of amino acid order on chiral selectivity in polymeric dipeptide
      surfactants, as well as the physical properties of the surfactants, is
      investigated. An understanding of enantioselectivity of such dipeptide
      surfactants is crucial to the design of more efficient polymeric surfactants and
      has implications in other areas of research such as enantioselective interactions
      of amino acid based compounds (i.e., enzymes, hemoglobin, antibodies, etc.). It
      should be noted that such polymeric surfactants are not easily crystallized.
      Therefore, in a manner similar to the study of proteins, fluorescence
      spectroscopy is a powerful tool used to study the structure-function relationship
      of these polymeric surfactants. The microenvironments inside the core of 18
      polymeric surfactants were characterized using the environmentally sensitive
      probes pyrene and 6-propionyl-2-(dimethylamino)naphthalene (Prodan). The
      surfactants examined in this study include all possible dipeptide combinations of
      the L-form of alanine, valine, and leucine and the achiral amino acid glycine
      (except glycine-glycine) as well as the single amino acid surfactants of alanine,
      valine, and leucine. The results of the fluorescent probe studies led to a
      proposed structure of the polymeric dipeptide surfactants in solution. The
      implications of the proposed structure for chiral selectivity were tested with
      two model atropisomers, (+/-)1,1'-bi-2-naphthol and (+/-)1,1'-bi-2-naphthyl-2,2'
      diyl hydrogen phosphate, using capillary electrokinetic chromatography.

PMID- 10204031
TI  - Pteridine analysis in urine by capillary electrophoresis using laser-induced
      fluorescence detection.
AB  - Pteridines are a class of compounds excreted in urine, the levels of which are
      found to elevate significantly in tumor-related diseases. For the first time, we
      have developed a method, based on high-performance capillary electrophoresis
      (HPCE) and laser-induced fluorescence (LIF) detection, to monitor the pteridine
      levels in urine. HPCE provides better separation than high-performance liquid
      chromatography and the LIF detector enables us to detect minute amounts of
      pteridines in body fluid. Eight different pteridine derivatives were well
      separated in 0.1 M Tris-0.1 M borate-2 mM EDTA buffer (pH 8.75) using a 60-cm
      fused-silica capillary (50-micron i.d., 35-cm effective length), six of which
      were detected and characterized in urine samples from normal persons and
      different cancer patients. The detection limits of these pteridines are under 1 x
      10(-10) M. The levels of neopterin, pterine, xanthopterin, and pterin-6
      carboxylic acid were found to be significantly elevated in urine excreted by
      cancer patents, while the level of isoxanthopterin dropped in these patients. No
      significant change of biopterin level was found between healthy individuals and
      cancer patients. This method can be used in clinical laboratories either for
      cancer monitoring or for precancer screening.

PMID- 10204032
TI  - Characterization of chemical selectivity in micellar electrokinetic
      chromatography. 4. Effect of surfactant headgroup.
AB  - The influence of surfactant headgroups on migration behavior in micellar
      electrokinetic chromatography is examined. Using linear solvation energy
      relationships (LSER) and functional group selectivity studies, the effect of six
      anionic headgroups on chemical selectivity is characterized. The sodium dodecyl
      surfactants of the sulfate [SO4-], sulfonate [SO3-], carboxylate [CO2-], carbonyl
      valine [OC(O)NHCH(CH(CH3)2)CO2-], and sulfoacetate [OC(O)CH2SO3-] anions are
      investigated. Solute size and the hydrogen-bond-donating ability of the micellar
      phase play the most significant roles in solute retention in all of the
      surfactants studied. While solute-micelle hydrogen bonding plays a dominant role
      in the observed selectivity, the dipolarity and polarizability of the micellar
      phase also have a small influence. The results also suggest that the hydrogen
      bond-accepting ability for surfactants is inversely proportional to the proton
      acidity (pKa) of its headgroup. The observed hydrogen-bond-donating ability and
      dipolarity of surfactant systems are believed to be a result of the water that
      resides near the micelle surface.

PMID- 10204033
TI  - On-bead combinatorial approach to the design of chiral stationary phases for
      HPLC.
AB  - A library of 36 L-amino acid anilides, which are potential selectors for chiral
      HPLC, was synthesized in solution and attached to functionalized macroporous
      polymer beads. The best selector from the library was identified by a
      deconvolution process using the HPLC separation of several racemic N-(3,5
      dinitrobenzoyl)-alpha-amino acid alkylamides as a probe. In each deconvolution
      step, a series of chiral stationary phases (CSPs) containing a subset of the
      amino acid anilide selector library was screened for enantioselectivity. After
      the best CSP was chosen, the library was further deconvoluted until the single
      best selector was found. The highest selectivity was obtained with a L-proline-1
      indananilide that exhibited alpha values up to 23 under normal-phase HPLC
      conditions. In addition, six CSPs were prepared using individual selectors from
      the library, and screening results indicate that the deconvolution process indeed
      led to the most selective receptor.

PMID- 10204034
TI  - Determination of chemical warfare agent degradation products at low-part-per
      billion levels in aqueous samples and sub-part-per-million levels in soils using
      capillary electrophoresis.
AB  - A significant enhancement in the method detection limits is observed in the
      analysis of chemical warfare agent (CWA) degradation products in environmental
      samples by capillary electrophoresis (CE) using electrokinetic injection. The CE
      method uses indirect UV detection of the nonderivitized acidic analyte and a
      cationic surfactant, didodecyldimethylammonium hydroxide, for reversal of the
      electroosmotic flow. Analytes studied include the dibasic acid methylphosphonic
      acid (MPA) and its monoacid/monoalkyl esters, RMPA, where R = ethyl, isopropyl,
      and pinacolyl (2-(3,3-dimethylbutyl)). The CE method uses an attractive buffer
      system which is highly stable and inexpensive, and, in addition to reversing the
      electroosmotic flow, provides excellent separation efficiencies within a 3-min
      run. This CE method is also free from interference caused by carbonate, humic
      acids, and fluoride. Compared to pressure injection, electrokinetic injection
      with this CE buffer system provided substantially lower detection limits, up to
      100-fold lower for samples in reagent water. However, to best realize the
      benefits of the electrokinetic injection enhancement for environmental samples, a
      prior cleanup of the sample using standard ion-exchange cartridges is necessary.
      This cleanup step uses sequential cartridges to remove sulfate (barium
      cartridge), chloride (silver cartridge), and cations (H+ cartridge). Using this
      approach, detection limits for these four acids were as low as 1-2 micrograms/L
      for water samples and 25-50 micrograms/L for aqueous leachates of soil samples
      (10 mL of leachate/1.5 g of soil). The utility of this method for separation of
      CWA degradation products by CE is discussed in terms of pressure injection versus
      electokinetic injection. The effects of voltage and time of injection on the
      separation were investigated. Results from three types of soils and four types of
      water (groundwater, artificial seawater, tap water, bay water) indicated that the
      method has potential for environmental monitoring. Quantitative CE analysis with
      electrokinetic injection enhancement of detection limits of these types of
      environmental samples requires the use of an appropriate internal standard
      approach. The data presented here indicate that an internal standard-based
      approach could be expected to give analysis results in the sub-part-per-million
      concentration range of 90-110% of the true value.

PMID- 10204035
TI  - Automated detection of anti-double-stranded DNA antibody in systemic lupus
      erythematosus serum by flow immunoassay.
AB  - We describe a novel automated flow immunoassay system for quantification of anti
      double-stranded (ds) DNA autoimmune antibodies in the serum of patients suffering
      from systemic lupus erythematosus. dsDNA (360 bp) was covalently coupled with
      alkaline phosphatase (ALP) to form a novel analytical reagent (ALP-DNA). After
      immunoreaction, antibody-antigen complexes between ALP-DNA and anti-dsDNA
      monoclonal antibody were separated from unreacted ALP-DNA by an ion-exchange
      column on the basis of the difference in isoelectric point. Antibody-antigen
      complexes were subsequently quantified by luminescence following addition of 3
      (2'-spiroadamantane)-4-methoxy-4-(3"-phosphoryloxy)phenyl- 1,2-dioxetane. The
      assay yielded a linear relationship between signal and concentration of anti
      dsDNA monoclonal antibody in the range of 0-300 micrograms/mL. This simple
      technique permits the assay of anti-dsDNA autoimmune antibodies within 25 min.
      The ion-exchange column was simply regenerated by occasional elution with eluent
      (20 mM N-methylpiperazine, pH 5.5) supplemented with 0.5 M NaCl, to remove
      unreacted ALP-DNA.

PMID- 10204036
TI  - Supercritical fluid extraction and gas chromatography/mass spectrometry for the
      analysis of tobacco-specific nitrosamines in cigarettes.
AB  - A method for measuring four tobacco-specific nitrosamines (TSNAs), an important
      group of compounds in tobacco products, was developed. These compounds were
      extracted using supercritical fluid extraction (SFE) and purified by a sodium
      hydroxide wash of the ethyl acetate eluting solvent and solid-phase extraction.
      Quantitation was performed using gas chromatography/mass spectrometry (GC/MS).
      Spiking experiments were carried out to determine the recovery, precision, and
      limits of detection of this method. The detection limits were 0.04 microgram per
      sample for N'-nitrosonornicotine and N'-nitrosoanatabine and 0.02 microgram for 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone and N'-nitrosoanabasine. This method
      was used to measure TSNAs in various brands of cigarette tobacco with excellent
      reproducibility. The variation of TSNA levels among the cigarettes of different
      packs and types was significantly smaller than that among different brands.
      Comparable TSNA levels were obtained with SFE and liquid extraction methods.
      Signal-to-noise levels were similar for GC/MS and GC/thermal energy analysis when
      low-level tobacco samples were analyzed.

PMID- 10204037
TI  - High resolution of DL-tryptophan at high flow rates using a bovine serum albumin
      multilayered porous hollow-fiber membrane.
AB  - We describe a bovine serum albumin (BSA)-multilayer-adsorbed porous hollow-fiber
      membrane as a stationary phase that enables chiral separations at a high
      resolution and high rate. Epoxy-group-containing graft chains were uniformly
      immobilized on the surface of pores throughout a porous hollow-fiber membrane by
      radiation-induced graft polymerization. Subsequently, a diethylamino group as an
      anion-exchange moiety was introduced to the graft chains, which caused the chains
      to expand toward the interior of the pores due to mutual electrostatic repulsion.
      The expanding polymer chains provided multilayer binding sites for BSA as a
      chiral selector. BSA with a degree of multilayer binding of 4 specifically
      recognized L-tryptophan with a separation factor of 6.6 during permeation by a
      mobile phase (Tris-HC1 buffer) injected with a racemic solution of DL-tryptophan
      through the BSA-multilayered porous membrane. In addition, the separation factor
      was constant irrespective of flow rates of the mobile phase because of negligible
      diffusional mass-transfer resistance of tryptophan to BSA multilayered by the
      graft chains.

PMID- 10204038
TI  - Mercuracarborand "anti-crown ether"-based chloride-sensitive liquid/polymeric
      membrane electrodes.
AB  - Highly sensitive and selective chloride liquid/polymeric membrane electrodes are
      described that employ [9]-mercuracarborand-3 (MC3), a neutral preorganized
      macrocyclic Lewis acid, as the anion carrier. MC3-based chloride-sensitive
      membrane electrodes, doped with different mole percentages of cationic additives
      (5, 10, and 60 mol % tridodecylmethylammonium chloride) relative to the amount of
      the carrier, exhibit enhanced potentiometric selectivity for chloride over other
      anions, including more lipophilic anions such as perchlorate, nitrate, and
      thiocyanate. In addition, the selectivity coefficients obtained are shown to meet
      the requirement for clinical applications. The obtained selectivity pattern is
      shown to correlate very well with 199Hg NMR titrations of MC3 with various
      anions, performed in organic solvents. Optimized membrane electrodes show a near
      Nernstian response toward chloride over a wide concentration range and have
      micromolar detection limits. MC3-based chloride sensors show a fast response time
      (in the order of few seconds), as well as short recovery time. The developed
      mercuracarborand-based sensors do not practically respond to pH changes over the
      pH range of 2.5-7.0. Response characteristics (e.g., detection limit, linear
      range, response slope, and selectivity) of the [9]mercuracarborand-3 based
      chloride sensors remain essentially the same over a period of approximately 2
      months, reflecting remarkable stability and well-defined chemistry of the
      macrocyclic Lewis acid ionophore.

PMID- 10204039
TI  - Preliminary investigation of electrothermal vaporization sample introduction for
      inductively coupled plasma time-of-flight mass spectrometry.
AB  - The coupling of an electrothermal vaporization (ETV) apparatus to an inductively
      coupled plasma time-of-flight mass spectrometer (ICP-TOFMS) is described. The
      ability of the ICP-TOFMS to produce complete elemental mass spectra at high
      repetition rates is experimentally demonstrated. A signal-averaging data
      acquisition board is employed to rapidly record complete elemental spectra
      throughout the vaporization stage of the ETV temperature cycle; a solution
      containing 34 elements is analyzed. The reduction of both molecular and atomic
      isobaric interferences through the temperature program of the furnace is
      demonstrated. Isobaric overlaps among the isotopes of cadmium, tin, and indium
      are resolved by exploiting differences in the vaporization characteristics of the
      elements. Figures of merit for the system are defined with several different data
      acquisition schemes capable of operating at the high repetition rate of the TOF
      instrument. With the use of both ion counting and a boxcar averager, the dynamic
      range is shown to be linear over a range of at least 6 orders of magnitude. A
      pair of boxcar averagers are used to measure the isotope ratio for silver with a
      precision of 1.9% RSD, despite a cycle-to-cycle precision of 19% RSD. Detection
      limits of 10-80 fg are calculated for seven elements, based upon a 10-microL
      injection.

PMID- 10204040
TI  - Trace analyses of arsenic in drinking water by inductively coupled plasma mass
      spectrometry: high resolution versus hydride generation.
AB  - A magnetic sector inductively coupled plasma mass spectrometer (ICPMS) was
      applied to the determination of arsenic in drinking water samples using standard
      liquid sample introduction in the high-resolution mode (M/delta M = 7800) and
      hydride generation in the low-resolution mode (M/delta M = 300). Although high
      mass resolution ICPMS allowed the spectral separation of the argon chloride
      interference, the accompanying reduction in sensitivity at high resolution
      compromised detection and determination limits to 0.3 and 0.7 microgram/L,
      respectively. Therefore, a hydride generation sample introduction method,
      utilizing a new membrane gas-liquid separator design, was developed to overcome
      the chloride interference. Due to the high transport efficiency and the 50-100
      times higher sensitivity at M/delta M = 300, the HG-ICPMS method resulted in an
      over 2000-fold increase in relative sensitivity. The routine detection and
      quantification limits were 0.3 and 0.5 ng/L, respectively. The results for both
      methods applied to the analysis of over 400 drinking water samples showed very
      good agreement at concentrations above 1 microgram/L. For concentrations between
      0.01 and 1 microgram/L, only HG-ICPMS provided accurate quantitative results.
      Membrane desolvation, mixed-gas plasmas, and the addition of organic solvents for
      the reduction of the ArCl+ interference were also investigated and evaluated for
      trace As determination.

PMID- 10204041
TI  - Sequencing of partially methyl-esterified oligogalacturonates by tandem mass
      spectrometry and its use to determine pectinase specificities.
AB  - Complex mixtures of acidic oligosaccharides were produced by enzymatic digestion
      of partially methyl-esterified pectin with Aspergillus niger pectin lyase,
      endopolygalacturonase II, and exopolygalacturonase. To determine the
      specificities of these pectolytic enzymes toward non-esterified and methyl
      esterified galacturonic acid residues, we have studied the methyl esterification
      patterns of selected oligomers in unseparated pectin digests. Collision-induced
      dissociation in a nanoelectrospray ionization ion trap mass spectrometer was used
      to locate methyl-esterified galacturonic acid residues in oligomers up to a
      degree of polymerization of 10. Analysis of the methyl esterification patterns
      gave insight into the substrate specificities of these pectolytic enzymes.
      Isomeric fragment ions containing the reducing and nonreducing ends were
      differentiated by 18O-labeling of the reducing end.

PMID- 10204042
TI  - 18O-labeling of N-glycosylation sites to improve the identification of gel
      separated glycoproteins using peptide mass mapping and database searching.
AB  - Peptide mass mapping using matrix-assisted laser desorption/ionization (MALDI)
      mass spectrometry in conjunction with interrogation of sequence databases is a
      powerful tool for the identification of proteins. Glycosylated proteins often
      yield poor MALDI peptide maps due to shielding of proteolytic cleavage sites and
      the presence of modified peptides. Here we demonstrate that enzymatic removal of
      N-linked glycans with simultaneous partial (50%) 18O-labeling of glycosylated
      asparagine residues prior to proteolysis and MALDI peptide mass mapping can
      overcome these problems. As a result, more peptides are observed in MALDI spectra
      which, in turn, increases the specificity of subsequent database searches.
      Furthermore, the detection of a labeled peptide directly translates into partial
      sequence information as N-linked carbohydrates are exclusively attached to
      asparagine residues that form part of the NXS/T sequence. The mass of the
      formerly glycosylated peptide together with the NXS/T sequence pattern represents
      a discriminating criterion for database searching which, on average, increases
      the search specificity by a factor of 100. This procedure allows the unambiguous
      identification of glycoproteins that would otherwise require sequencing and, at
      the same time, enables the identification of N-glycosylation sites with higher
      sensitivity than previously possible.

PMID- 10204043
TI  - Determination of nearest neighbors in nucleic acids by mass spectrometry.
AB  - The identification of nearest-neighbor residues in nucleic acids provides useful
      constraints on establishment of base composition and sequence and is potentially
      applicable to a range of structural problems involving synthetic and natural
      polynucleotides. A new approach to this problem using electrospray ionization
      tandem mass spectrometry is based on measurement of precursor-product
      relationships derived from small fragment ions produced in the high-pressure
      ionization ("nozzle-skimmer") region of the instrument. Measured mass values of
      dinucleotide or other fragments, which give rise to mononucleotide ions N formed
      in the collision cell and transmitted by the second mass analyzer, establish the
      identities of residues adjacent to N. The technique is applicable to RNA and DNA,
      whether modified, or not, and is demonstrated using modified residues in nucleic
      acids up to the size of intact tRNA (76-mer). By monitoring of selected ion
      reaction channels, the method has been extended to LC/MS and to nearest-neighbor
      determinations directly in oligonucleotide mixtures.

PMID- 10204044
TI  - Lectin-based affinity capture for MALDI-MS analysis of bacteria.
AB  - Immobilized lectins have now been incorporated into affinity surfaces that can be
      used to isolate broad classes of samples for mass spectrometric analysis. A
      carbohydrate and a bacterial species that displays the carbohydrate binding motif
      were isolated and concentrated out of solutions containing salt, urea, buffers,
      and other contaminants that are deleterious to MALDI mass spectrometry.
      Concanavalin A was immobilized to a gold foil via a self-assembled monolayer.
      Samples in phosphate buffer or urine were applied to the capture surface and
      allowed to interact. The capture surface was then washed to remove salts and
      other unbound components and subjected to matrix-assisted laser
      desorption/ionization on a time-of-flight mass spectrometer. The lectin
      derivatized surface allowed samples to be concentrated and readily characterized
      at relatively low levels.

PMID- 10204045
TI  - Microfabricated filters for microfluidic analytical systems.
AB  - Solvent and reagent filters were micromachined into quartz wafers using deep
      reactive ion etching to create a network of intersecting 1.5 x 10 microns
      channels. When placed at the bottom of reservoirs with a side exit, this channel
      network behaved as a lateral percolation filter composed of an array of cubelike
      structures one layer deep. Flow through these filters was driven by
      electroosmotic flow (EOF). Silanol groups at the walls of channels in the network
      provided the requisite charge to trigger EOF when voltage was applied laterally
      to the filter. Adsorption of cationic proteins in this silanol-rich matrix was
      controlled by the application of a polyacrylamide coating prepared by bonding N
      hydroxysuccinimide (NHS)-activated poly(acrylic acid) to (gamma
      aminopropyl)silane-derivatized filters. Subsequent reaction of residual NHS
      groups in the coating with 2-(2-aminoethoxy)ethanol provided channels of low
      charge density and adsorptivity. These lateral percolation filters were shown to
      be efficacious in filtering solvents containing a variety of particulate
      materials, ranging from dust to cells.

PMID- 10204047
TI  - Society of Cardiovascular Anesthesiologists 21st annual meeting. Chicago,
      Illinois, USA. April 24-28, 1999. Abstracts.

PMID- 10204046
TI  - On-target exoglycosidase digestions/MALDI-MS for determining the primary
      structures of carbohydrate chains.
AB  - One method used to determine the primary sequence of oligosaccharides is to
      digest them with exoglycosidases and analyze the resulting digestion products by
      matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
      Previous research has demonstrated that these digestions can be performed on the
      MALDI target. However, the procedure requires the sample to be incubated at
      elevated temperatures, and complete digestion requires a few hours. We
      demonstrate new conditions that permit exoglycosidase digestions to be performed
      on the MALDI target at room temperature within 30 min. Oligosaccharide standards
      were digested with one or more exoglycosidases to show that the enzymes retain
      their activity and specificity under these new reaction conditions. Using this
      method, the primary sequences of carbohydrate chains can be determined in a
      relatively short amount of time.

PMID- 10204048
TI  - A review of Chlamydia pneumoniae and atherosclerosis.
AB  - Chlamydia pneumoniae is a Gram-negative obligate intracellular bacterium that
      causes acute upper and lower respiratory infections. Its distribution is
      worldwide. Seroepidemiological studies have shown an association between C.
      pneumoniae and atherosclerosis, and the risk of acute myocardial infarction.
      Several studies had detected C. pneumoniae in atherosclerotic lesions from
      coronary and carotid arteries, in abdominal aortic aneurysms (AAA), and in
      sclerotic aortic valves. One study consistently succeeded in culturing C.
      pneumoniae from an atherosclerotic lesion, indicating the presence of viable
      organisms. However, the pathogenicity is unknown, and the significance of
      detecting the organism is unresolved. In two minor controlled clinical trials,
      patients with ischaemic heart disease were randomised into antibiotic-treated and
      placebo groups. Both trials showed a significant reduction in serious endpoints
      in patients receiving macrolide. Macrolide therapy thus seems to improve the
      outcome of severe ischaemic heart disease. It is not known whether this is caused
      by eradicating C. pneumoniae organisms, or by the macrolide's non-specific anti
      inflammatory effect. Since both C. pneumoniae and inflammation are found in the
      AAA wall, it may be considered that macrolide would also improve the outcome of
      AAA and other diseases related to vascular surgery. In order to confirm this,
      randomised trials with macrolide therapy are needed, as well as diagnostic
      methods that can differentiate between individuals who are or are not infected
      with C. pneumoniae. The latter are needed in order to clarify the impact of the
      presence of C. pneumoniae and to avoid indiscriminate use of antimicrobials.

PMID- 10204049
TI  - Incidence and importance of lower extremity nerve lesions after infrainguinal
      vascular surgical interventions.
AB  - OBJECTIVES: To determine the incidence of peripheral nerve lesions after arterial
      vascular surgery of the lower extremity. MATERIALS AND METHODS: 436 patients who
      underwent peripheral vascular surgery from January 1992 until December 1996
      underwent a detailed postoperative neurological examination. RESULTS: 147
      patients underwent profundaplasty, 140 above-knee femoropopliteal bypasses, 106
      below-knee femoropopliteal bypasses and 56 femorotibial bypasses. There were 182
      women and 254 men. Peripheral nerve lesions were observed in 11 patients (4%)
      after primary operations. 166 patients underwent reoperations (38%) and 55 of
      these developed nerve lesions (33%). CONCLUSIONS: Reoperation carries an 8-fold
      increased risk of nerve lesions compared with patients undergoing primary
      surgery. Detailed explanation of the risk of peripheral nerve lesions before
      vascular surgery of the lower limb is advisable.

PMID- 10204050
TI  - Cytokine and fibrinogen response in patients undergoing open abdominal aortic
      aneurysm surgery.
AB  - OBJECTIVES: To assess whether open abdominal aortic aneurysm (AAA) surgery
      influences cytokines and fibrinogen. METHODS: Twenty-three consecutive patients
      operated on for AAA were compared to 11 operated controls and 20 age-matched
      controls. Cubital blood was sampled pre-, intra- and postoperatively and femoral
      blood also sampled intraoperatively. RESULTS: Preoperatively, interleukin (Il)-6
      was elevated in AAA patients. During aortic clamping, Il-6, Il-10 and monocyte
      chemoattractant protein-1 (MCP-1) increased significantly (p < 0.001, p < 0.01
      and p < 0.05 respectively) while soluble interleukin-2 receptor (sIl-2R) and
      fibrinogen decreased significantly (p < 0.001 for both). After aortic declamping,
      Il-6, Il-10 and MCP-1 had further significant increases compared with levels
      during aortic clamping while sIl-2R had a further non-significant and fibrinogen
      a significant decrease (p < 0.05 in cubital and p < 0.001 in femoral blood). One
      week postoperatively Il-6, Il-10 and MCP-1 had all decreased but were still
      significantly elevated compared with baseline values while sIl-2R and fibrinogen
      showed an increase in comparison with baseline (p < 0.001 for both).
      Intraoperative levels of Il-6 and Il-10 showed a significant co-variation with
      the magnitude of operative trauma. CONCLUSIONS: These data indicate that open AAA
      surgery induces a profound inflammatory and coagulative response which persists
      at one week postoperatively.

PMID- 10204052
TI  - Sexual function in women suffering from aortoiliac occlusive disease.
AB  - OBJECTIVE: To describe the sexual function in women suffering aortoiliac
      occlusive disease (AIOD) and in an age-matched reference group. PATIENTS AND
      METHODS: Thirty-six women suffering from AIOD were included. Twenty were
      investigated before vascular intervention (untreated) and 16 different women
      after treatment (treated). Eighteen age-matched women served as a reference
      group. The patients answered a questionnaire including sexual, social and medical
      questions and a gynaecological examination was performed. RESULTS: Untreated
      patients with AIOD have a significantly impaired physical well-being compared to
      the other groups (p < 0.001). A negative effect of the vascular disease and its
      treatment on sexual life was experienced by 69% of treated compared to 40%
      affected among untreated (p = 0.05). Vulval sensibility was impaired in 44% of
      treated, 11% of untreated and 22% of reference patients. Defective anal sphincter
      function was found in 33% of treated, 17% of untreated and 6% in the reference
      group. Those differences were not statistically significant. CONCLUSIONS:
      Symptomatic AIOD in women is associated with a significantly impaired physical
      and sexual well-being. Though limited by size and methodology, the results
      indicate the possibility of iatrogenic nerve damage.

PMID- 10204051
TI  - Transcranial Doppler directed dextran therapy in the prevention of carotid
      thrombosis: three hour monitoring is as effective as six hours.
AB  - BACKGROUND: Six hours' monitoring by transcranial Doppler (TCD) has been
      successful in directing Dextran therapy in patients at high risk of thrombotic
      stroke after carotid endarterectomy (CEA). OBJECTIVES: Is 3 h of routine
      monitoring as effective as 6 h in the prevention of early postoperative
      thrombotic stroke? DESIGN: Prospective, consecutive study in all patients with an
      accessible cranial window. METHODS: One hundred and sixty-six patients undergoing
      CEA underwent 3 h of postoperative monitoring by TCD. Any patient with > 25
      emboli detected in any 10 min period or those with emboli that distorted the
      arterial waveform were commenced on an incremental infusion of dextran 40.
      RESULTS: The majority of patients destined to embolise will do so within the
      first 2 postoperative hours. Dextran therapy was instituted in nine patients (5%)
      and rapidly controlled this phase of embolisation although the dose had to be
      increased in three (33%). No patient suffered a postoperative carotid thrombosis
      but one suffered a minor stroke on day 5 and was found to have profuse
      embolisation on TCD; high dose dextran therapy was again instituted, the embolus
      count rate fell rapidly and he made a good recovery thereafter. Overall, the
      death and disabling stroke rate was 1.2% and the death/any stroke rate was 2.4%.
      CONCLUSION: Three hours of postoperative TCD monitoring is as effective as 6 h in
      the prevention of postoperative carotid thrombosis.

PMID- 10204053
TI  - Endothelial activation response to oral micronised flavonoid therapy in patients
      with chronic venous disease--a prospective study.
AB  - BACKGROUND: Endothelial activation is important in the pathogenesis of skin
      changes due to chronic venous disease (CVD). Purified micronised flavonoid
      fraction has been used for symptomatic treatment of CVD for a considerable period
      of time. The exact mode of action of these compounds remains unknown. AIM: To
      study the effects of micronised purified flavonoidic fraction (Daflon 500 mg,
      Servier, France) treatment on plasma markers of endothelial activation. MATERIALS
      AND METHODS: Twenty patients with chronic venous disease were treated for 60 days
      with DAFLON 500 mg twice daily. Duplex ultrasonography and PPG was used to assess
      the venous disease. Blood was collected from a foot vein immediately before
      starting treatment and within 1 week of stopping treatment. Plasma markers of
      endothelial activation were measured using commercial ELISA kits. RESULTS:
      Reduction in the level of ICAM-1, 32% (141 ng/ml: 73 ng/ml) and VCAM 29% (1292
      ng/ml: 717 ng/ml) was seen. Reduction in plasma lactoferrin (36% decrease, 760
      ng/ml: 560 ng/ml) and VW factor occurred in the C4 group only. CONCLUSIONS:
      Micronised purified flavonoidic fraction treatment for 60 days seems to decrease
      the levels of some plasma markers of endothelial activation. This could
      ameliorate the dermatological effects of (CVD). This could also explain some of
      the pharmacological actions of these compounds. Our study demonstrates the
      feasibility of using soluble endothelial adhesion molecules as markers for
      treatment.

PMID- 10204054
TI  - Quality of life associated with varying degrees of chronic lower limb ischaemia:
      comparison with a healthy sample.
AB  - OBJECTIVES: To assess quality of life in patients with varying degrees of
      ischaemia in comparison with controls, and to determine whether the degree of
      lower limb ischaemia and sense of coherence were associated with quality of life.
      MATERIALS AND METHODS: 168 patients, including 93 claudicants and 75 patients
      with critical ischaemia and 102 controls were studied. Quality of life was
      assessed using the Nottingham Health Profile in addition to the Sense of
      Coherence scale. MAIN RESULTS: Patients with lower limb ischaemia scored
      significantly reduced quality of life in all aspects compared to controls. Pain,
      physical mobility and emotional reactions were the significant independent
      factors when using logistic regression analysis. The grade of disease and low
      sense of coherence were significantly associated with low quality of life.
      Increasing lower limb ischaemia significantly conferred worse pain, sleeping
      disturbances and immobility. CONCLUSION: This study showed that the quality of
      life was impaired among patients with lower limb ischaemia, in all investigated
      respects. The degree to which quality of life was affected seems to represent an
      interplay between the grade of ischaemia and the patient's sense of coherence.
      This suggests the need for a multidimensional assessment prior to intervention.

PMID- 10204056
TI  - Movement-related variation in forces under compression stockings.
AB  - OBJECTIVES: Compression therapy is widely used in the treatment of venous leg
      ulcers, but the efficacy of this treatment is variable. Assessment of variation
      in compression forces associated with movement may help to elucidate the
      mechanism of action of compression therapy. The aim of this study was to develop
      and apply a system to investigate forces under compression stockings during
      movement. METHOD: Three sensors were placed on the medial aspect of the left leg
      on six healthy volunteers to monitor forces under class 2 (Continental European
      classification) compression stockings. Data were recorded during dorsiflexion and
      plantar flexion of the left foot and also during short periods of walking.
      RESULTS: Changes in pressure were observed, associated with dorsiflexion and
      plantar flexion of the foot. These changes were dependent on sensor position.
      Changes in pressure during walking were also position-dependent and of variable
      duration. CONCLUSIONS: The system enables forces associated with compression
      therapy to be examined during movement and may thus be of value in further
      understanding its mechanism of action. Foot movement can be associated with clear
      changes in pressure under compression stockings and rapid changes in pressure may
      occur during walking.

PMID- 10204055
TI  - Cardiovascular and catecholamine responses during endovascular and conventional
      abdominal aortic aneurysm repair.
AB  - OBJECTIVES: To compare changes in plasma catecholamines, acid-base status and
      cardiovascular dynamics in patients undergoing endovascular or conventional
      infrarenal abdominal aortic aneurysm (AAA) repair under standard general
      anaesthesia. DESIGN: Prospective cohort study. MATERIALS: 30 patients scheduled
      for elective infrarenal AAA repair. METHODS: Plasma epinephrine and
      norepinephrine concentrations, acid-base status and cardiovascular measurement
      were compared before surgery, and 5 min after aortic clamping and clamp release
      (conventional group) or occlusion and release (endovascular group) in patients
      undergoing endovascular (n = 15) or conventional AAA repair (n = 15). RESULTS:
      Arterial pH (p < 0.005) and base deficit (p < 0.05) increased, and plasma
      bicarbonate decreased (p < 0.005) during aortic cross-clamping in the
      conventional group. pH decreased further (p < 0.005), and base deficit and pCO2
      increased (both p < 0.005) after clamp release. These changes were significantly
      greater than during endovascular repair, in whom within-group changes were not
      statistically significant. Values were similar in the two groups 30 min after
      reperfusion. Plasma epinephrine concentrations increased during conventional
      surgery (p < 0.05) and were greater than in the endovascular group (p < 0.05).
      Plasma norepinephrine concentrations increased during surgery in both groups but
      the changes were not statistically significant. CONCLUSIONS: Plasma catecholamine
      concentrations, changes in cardiovascular variables and acid-base status were
      increased during conventional compared with endovascular AAA repair.

PMID- 10204057
TI  - Late survival after abdominal aortic aneurysm repair.
AB  - OBJECTIVES: This study was undertaken to determine the late survival of patients
      operated successfully for abdominal aortic aneurysm (AAA) repair, to compare
      survival data with that of the age- and sex-matched general population, to
      identify the causes of late death, and to determine the factors influencing late
      survival. MATERIALS AND METHODS: A total of 187 consecutive patients underwent
      elective surgical AAA repair between January 1987 and December 1991. There were
      11 postoperative deaths (early mortality rate 5.9%). The remaining 176 patients
      formed the basis of this cohort-based retrospective study. Six patients (3.4%)
      were lost to follow-up. Mean follow-up was 71 months. RESULTS: A total of 70
      patients (39.8%) died during the study period. Coronary artery disease (CAD) and
      cancer were the two main causes. The survival rate at five years (71.6%) was
      lower than that of the sex- and age-matched general population (90.6%). Neither
      arterial hypertension nor CAD had any influence on late survival. In contrast,
      age and chronic renal failure were predictive variables of late survival.
      CONCLUSIONS: The life expectancy of patients who undergo successful AAA repair is
      not as good as that of the age- and sex-matched general population. Late survival
      depends on the patients' age at the time of surgery and the existence of
      preoperative chronic renal failure.

PMID- 10204058
TI  - The results of thoracoscopic sympathetic trunk transection for palmar
      hyperhidrosis and sympathetic ganglionectomy for axillary hyperhidrosis.
AB  - OBJECTIVES: To review our total experience of thoracoscopic sympathetic trunk
      transection for the treatment of palmar hyperhidrosis and second and third
      thoracic sympathetic ganglionectomy for axillary hyperhidrosis. DESIGN:
      Longitudinal cohort study following up consecutive patients for 0.3 to 5.5 years.
      SUBJECTS: Fifty-four consecutive patients undergoing thoracoscopic sympathectomy
      for hyperhidrosis. METHODS: Prospective evaluation of immediate technical
      success, complications, late recurrence of hyperhidrosis and patient
      acceptability. RESULTS: 100% initial cure for palmar hyperhidrosis, 91% of
      sympathetic ganglionectomies for axillary hyperhidrosis were technically
      successful and initially curative. Compensatory sweating 44% patients, most
      severe after bilateral sympathetic ganglionectomy. Complications occurred in 14%
      patients, all resolving without further intervention. There were no cases of
      Horner's syndrome. 13% patients reported a return of some palmar sweating. 5.4%
      patients developed recurrent palmar hyperhidrosis at 6, 15 and 21 months
      postoperatively. CONCLUSION: Transection of the sympathetic trunk between the
      first and second thoracic sympathetic ganglia initially cures 100% of patients
      treated primarily for palmar hyperhidrosis. Technically successful 2nd and 3rd
      thoracic sympathetic ganglionectomy initially cures 100% of patients with
      axillary hyperhidrosis. Compensatory sweating is common after bilateral
      sympathectomy. Recurrent palmar hyperhidrosis occurs in 5.4% of cases, but can be
      cured by a second thoracoscopic sympathectomy. Horner's syndrome is an avoidable
      complication of thoracoscopic sympathectomy.

PMID- 10204059
TI  - A comparative study of the rifampicin binding and elution characteristics for
      collagen- and albumin-sealed vascular grafts.
AB  - OBJECTIVES: To assess the rifampicin binding and elution characteristics for
      three protein-sealed vascular grafts. DESIGN: In vitro study. MATERIALS: Cardial
      and Hemashield collagen-sealed and the DeBakey/Vasculour albumin-sealed vascular
      grafts. METHODS: The grafts were soaked in a 60,000 mg/l solution of rifampicin
      at 37 degrees C for 15 min. Bound drug was eluted from the grafts at 37 degrees C
      and at timed intervals the concentrations of rifampicin remaining in the grafts
      were determined. RESULTS: Although all three grafts contained high concentrations
      of rifampicin immediately after soaking these rapidly fell on washing and only a
      small fraction of the adsorbed rifampicin was tightly bound to the grafts.
      Rifampicin loading of this tightly bound fraction was similar for the two
      collagen-sealed grafts (1.7-2.0 mg/kg) but higher for the albumin-sealed graft
      (16.0 mg/kg). Elution of the tightly bound fraction appeared to follow first
      order kinetics with elimination half-lives of 89-141 h. The concentrations of
      rifampicin remaining in the grafts after eight days were above those needed to
      inhibit sensitive staphylococci and were 0.7 mg/kg (collagen-sealed grafts) to
      3.7 mg/kg (albumin-sealed graft). CONCLUSIONS: There is broad equivalence between
      the rifampicin binding and elution for the two collagen-sealed grafts, but there
      appears to be slightly higher binding for the albumin-sealed graft.

PMID- 10204061
TI  - Saddle embolus of the carotid bifurcation. A late complication of mediastinal
      radiotherapy.

PMID- 10204060
TI  - Aortoiliac stenting, determinants of clinical outcome.
AB  - OBJECTIVES: To determine predictors of clinical outcome in stenting aortoiliac
      disease. DESIGN: Prospective/retrospective study. MATERIALS AND METHODS: One
      hundred and forty patients (163 limbs) underwent iliac artery stenting in the
      period 1994-1997. Ninety-eight occlusions and 65 stenoses were treated, either
      with primary stenting (n = 129) or after failed angioplasty (n = 34). Median
      follow-up 18 months (1-66). Factors analysed for their effect on outcome were:
      gender, age, Fontaine stage, ABI, lesion type/length/site, primary or secondary
      stenting, stent type, BP, smoking, diabetes, aspirin, cholesterol, residual
      gradient, overhanging and run-off. RESULTS: The immediate success was 95%. The
      primary successful clinical outcome was 90% at 12 months and 84% at 36 months;
      the primary-assisted successful clinical outcome was 95% at 12 months and 91% at
      36 months and the secondary successful clinical outcome was 92% at 12 months and
      87% at 36 months. Adverse factors affecting outcome were: residual pressure
      gradient (> 10 mmHg) and no treatment with aspirin (p < 0.05). Major
      complications occurred in 18% of patients with a re-intervention in 8%. The 30
      day mortality was 5.5%. CONCLUSIONS: Stenting for aortoiliac occlusive disease
      has good short and long term clinical success, with low morbidity and mortality.
      Factors that might improve results further are ensuring that patients are taking
      aspirin and any residual pressure gradient is abolished.

PMID- 10204062
TI  - Subintimal recanalisation of a popliteal occlusion following a perforation and
      coil embolisation.

PMID- 10204063
TI  - A complication of the tapered aortouni-iliac graft for endovascular aneurysm
      repair.

PMID- 10204064
TI  - Advances in Genetics, cumulative subject index, volumes 20-39.

PMID- 10204065
TI  - Proceedings of the 26th International Conference on Animal Genetics. Auckland,
      New Zealand, 9-14 August 1998. Abstracts.

PMID- 10204066
TI  - The Contributions of the Vestibular System to Oculo-Motor, Skeleto-Motor and
      Perceptual Functions. Proceedings of a symposium in honour of Ottavio Pompeiano
      and Victor Wilson. Freiburg, Germany, September 9-11, 1998. Abstracts.

PMID- 10204067
TI  - Proceedings of the British Pharmacological Society meeting. University of
      Southampton. 8-11 September 1998. Abstracts.

PMID- 10204068
TI  - British Paediatric Neurology Association annual meeting 1999. Abstracts.

PMID- 10204070
TI  - VIth Lille Neurological Workshop: Dementias, Cerebrovascular Diseases, White
      Matter Changes. 27-28 November 1998. Abstracts.

PMID- 10204069
TI  - Growth Factors and Polyamines in Mucosal Protection and Repair, International
      symposium. Cracow, Poland, September 12, 1998. Abstracts.

PMID- 10204071
TI  - Analysis of photocontrol of aspartate kinase in barley (Hordeum vulgare L.)
      seedlings.
AB  - Aspartate kinase (AK) activity is regulated by light. The activity was more in
      light exposed barley seedlings than those grown in the dark. The light effect was
      manifested even with small exposures of 5 min duration and red light was more
      effective than white light in this respect. The effect of 5 min red light could
      be reversed by a 5 min pulse of far-red light indicating the involvement of
      phytochrome in this response. The phytochrome is also involved in long term light
      effects (24 hr exposures with white light). Ca++ takes part in the signal
      transduction pathway for this light response. Western blot analysis using
      antibodies raised against the purified lysine- and threonine-sensitive AK
      isoenzymes from spinach leaves showed no cross reaction with the antibodies to
      the threonine-sensitive AK in the dark and 5 min far-red light exposed seedlings.
      But the protein band was detected in the white and red lights. Northern blot
      analysis of seedlings grown under dark and exposed to white, red and far-red
      lights and probed with the gene encoding aspartokinase-homoserine dehydrogenase
      (AKHSD) protein indicated that the gene was differentially expressed. In dark
      grown seedlings, AKHSD transcript was in low concentration as compared to white
      light where the transcript concentration was high. A 5 min red light pulse
      increased the transcript concentration significantly in contrast to 5 min far-red
      light. The transcript concentration was reduced when 5 min red light was followed
      by a 5 min far-red light pulse. The AK activity in dark-raised seedlings is
      attributed to the presence of only one isoenzyme that is sensitive to lysine but
      insensitive to Ca++ and calmodulin (CAM). In both white and red light exposed
      seedlings, three isoenzymes of AK were detected. Two of these were sensitive to
      threonine while one was sensitive to lysine. Both of the threonine sensitive
      isoenzymes were activated by Ca++ and CAM. Also one of these isoenzymes seems to
      be located and synthesized in chloroplasts because its synthesis was completely
      inhibited by chloramphenicol but not by cycloheximide.

PMID- 10204072
TI  - Purification and characterization of a cell-surface lectin (Lectin II) from
      Agrobacterium radiobacter NCIM 2443.
AB  - A lectin was isolated from Agrobacterium radiobacter cell surface and purified.
      It is a monomer of 40 kDa as shown by SDS-PAGE. The lectin has a pI of 9.15 and
      amino acid composition of the lectin shows that 44% of the amino acids are
      hydrophobic. The lectin agglutinates rabbit erythrocytes but does not agglutinate
      human erythrocytes. It does not show specificity for monosaccharides except for D
      glucosamine. Fetuin and its N-linked glycopeptide also inhibit the activity of
      the lectin but greater inhibition is shown by locust bean gum and Nicotiana
      tobaccum (tobacco) tissue extracts.

PMID- 10204073
TI  - Structural characteristics of tenecin 3, an insect antifungal protein.
AB  - Tenecin 3, an antifungal protein, previously isolated from the insect Tenebrio
      molitor, inhibits growth of the fungus Candida albicans. However, the antifungal
      mechanism and functions of tenecin 3 remain unknown. As an initial step to study
      the mechanism and functions, physical and structural properties of tenecin 3 were
      examined by circular dichroism (CD) analysis and 2D nuclear overhauser effect
      spectroscopy. These analyses suggest that tenecin 3 has a propensity of random
      structure with very loose turn-like elements. The CD results also indicate that
      this random structural propensity is not significantly affected by temperature,
      pH, and by the presence of organic solvents or sodium dodecyl sulfate (SDS)
      micelles. However, the hydrodynamic studies suggest that tenecin 3 is not in
      extended form in spite of its random structural feature.

PMID- 10204074
TI  - Concanavalin A binding to oligosaccharide chain leads to alterations in
      properties of band 3.
AB  - Anion transport activity and thermotropic behavior of Band 3 are found to be
      altered after binding of concanavalin (Con A) to human erythrocyte ghosts and
      isolated Band 3. At lower Con A concentration, the rate coefficients of anion
      transport enhance with increasing Con A concentration, while noticeable changes
      of the largest calorimetric endotherm of human erythrocyte membranes termed the C
      transition (Band 3) can not be observed. With 50 micrograms/ml of Con A, the rate
      coefficient of Con A-modified ghosts increases 34.4% in comparison with that of
      normal ghosts. Binding of Con A in lower concentration to ghosts bring about
      increase of fluidity of lipid which maybe contribute to increase anion transport
      via Band 3. At higher Con A concentration, the C transition tend to lower
      temperature with increase in Con A concentration, the C transition is shifted
      from 69.25 degrees C to 66.25 degrees C with 2.5 mg/ml Con A. It is suggested
      that the Con A-modified Band 3 possess a looser structure than normal one.

PMID- 10204075
TI  - Degradation of an ubiquitin-conjugated protein is associated with myoblast
      differentiation in primary cell culture.
AB  - At the early stages of myogenesis, myoblasts fuse to form multinucleated
      myotubes. This morphological differentiation is the result of dynamic changes in
      gene regulation and expression. The ubiquitin proteasome-dependent pathway has
      been reported to play an important role in many aspects of cellular functions
      such as regulation of growth and cell cycle progression. In this study, we showed
      that the amount of mRNA's corresponding to the iota subunit of the 20S
      proteasome, the level of the S4 subunit of the 19S complex and the 20S and 26S
      proteasomes peptidase activities increased during myoblast fusion. Cell permeable
      20S proteasome inhibitor prevented fusion with concomitant accumulation of
      ubiquitin-conjugated protein. On the other hand, inhibition of ubiquitin ligase
      E3 enzymes prevented the formation of ubiquitin conjugate and decreased the
      fusion process. These results strongly support the involvement of the ubiquitin
      proteasome proteolytic pathway in the events leading to myoblast fusion.

PMID- 10204076
TI  - Different effects of the constituents of EGb761 on apoptosis in rat cerebellar
      granule cells induced by hydroxyl radicals.
AB  - The present study was conducted to evaluate the different effects of the
      constituents of EGb761 (Ginkgo biloba Extract) on apoptosis in cerebellar granule
      cells induced by hydroxyl radicals. The total flavonoid component of EGb761, two
      pure EGb761 components (rutin and quercetin), and a mixture of flavonoids and
      terpenes protected cerebellar granule cells from oxidative damage and apoptosis
      induced by hydroxyl radicals. ESR(electron spin resonance) results showed that
      the IC50 of the flavonoids for scavenging hydroxyl radicals was almost the same
      as that of EGb761, even though flavonoids make up only 24% of EGb761, implying
      that other constituents of EGb761 besides flavonoids can scavenge hydroxyl
      radicals. Total terpenes of EGb761 did not protect against apoptosis. Flavonoids
      and terpenes did not show a synergistic effect in this regard. Terpenes did not
      scavenge hydroxyl radicals directly, which might be related to their "cage-like"
      structures.

PMID- 10204078
TI  - Cloning, expression, and characterization of a cDNA encoding snake venom
      metalloprotease.
AB  - A cDNA clone, MT-c, encoding metalloprotease was isolated from snake (Agkistrodon
      halys brevicadus) venom gland cDNA library. Deduced amino acid sequence indicated
      that MT-c is composed of a signal sequence, amino-terminal propeptide, a central
      metalloprotease domain, and a Lys-Gly-Asp (KGD) disintegrin domain. The partial
      cDNA encoding metalloprotease and disintegrin domain was subcloned and expressed
      in E. coli. The expressed MT-c protein was purified and successfully refolded
      into functional form retaining the enzyme activity. Analyses of the purified
      recombinant protease activity revealed that the enzyme hydrolyzes extracellular
      matrix proteins including type I gelatin, type IV and type V collagen, while type
      I, II, III collagens and fibronectin were insensitive to the proteolytic
      digestion. The recombinant enzyme was also able to degrade fibrinogen by
      specifically cleaving A alpha chain of the protein.

PMID- 10204077
TI  - Isolation and characterization of cDNA clone for human liver 10
      formyltetrahydrofolate dehydrogenase.
AB  - A cDNA clone encoding 10-formyltetrahydrofolate dehydrogenase (10-FTHFDH) was
      isolated from a human fetal liver cDNA library. It contained the open reading
      frame of 2,709 base pairs and predicted a protein comprising 902 amino acids with
      a calculated molecular weight of 98,700 Da. The deduced protein showed about
      93.6% homology (90.5% identity, 3.1% favored substitutions) when compared with
      rat 10-FTHFDH. The distribution of 10-FTHFDH transcript in various human tissues
      was studied by Northern blot analysis using poly(A+) RNAs from different tissues.
      The 10-FTHFDH transcript with an approximate size of 2.7 kb was mainly expressed
      in human kidney, skeletal muscle, and liver and rarely expressed in other
      tissues.

PMID- 10204079
TI  - In vitro transcription assay with the purified 40kDa NF1-like protein binding to
      the rat p53 promoter.
AB  - The rat p53 promoter has several potential transcription factor-recognition
      motifs. They include NF1-like, bHLH family, and AP1-like proteins binding sites.
      The binding protein to NF1-like motif was previously identified. The protein has
      about 40kDa of molecular mass, which is smaller than that of NF1. Anti-NF1
      polyclonal antibody does not recognize the protein. In this study, we isolated
      the 40kDa protein by sequence-specific DNA affinity chromatography. The isolated
      protein was assayed by DNase I footprinting analysis. To determine the
      transactivation effect of the protein, in vitro transcription with the purified
      40kDa protein was carried out. After the addition of the purified 40kDa protein
      into the transcription reaction mixture, the transcription level of the p53
      promoter was increased. This suggests that the 40 kDa NF1-like protein is a
      transcription activator for the rat p53 gene.

PMID- 10204080
TI  - Modulation by nitric oxide (NO) of capsaicin-induced calcium uptake into rat
      dorsal root ganglion neurons.
AB  - The regulatory role of nitric oxide in capsaicin-induced 45Ca2+ accumulation in
      dorsal root ganglion neuronal cultures was investigated. Capsaicin-activated
      calcium entry was subject to complicated tuning by NO-releasing agents sodium
      nitroprusside, spermine/NO complex and NO synthase inhibitor NG-nitro-L-arginine
      methyl ester in concentration and stimulation protocol-dependent manner. In
      contrast, these agents failed to change depolarization-induced calcium influx. In
      experiments using dithiothreitol and 5,5-dithio-bis-2-nitrobenzoic acid this
      modulation was independent of the oxidizing action of NO. It is suggested that NO
      exerts a novel feedback modulatory effects on capsaicin-induced calcium entry
      into rat DRG neurons.

PMID- 10204081
TI  - Protein folding as a nonlinear nonequilibrium thermodynamic process.
AB  - Biofurcational theory of protein folding is developed describing the process of
      formation of protein native structure as a sequence of non-equilibrium
      irreversible fluctuations, specific for a particular protein. The model gives
      explanation to all characteristic features of the folding process: stochastic
      mechanism, short time and precision of proteins self-assembling. A constructive
      role of entropy in the formation of a highly ordered structure out of disorder is
      discussed. A numerical method of a priori calculations of polypeptide structures
      basing on principles of bifractional folding model is presented.

PMID- 10204082
TI  - Purification and characterization of a novel dipeptidyl peptidase from
      Dictyostelium discoideum.
AB  - A dipeptidyl peptidase (DPP) was purified to homogeneity using lys-ala-beta
      naphthylamide, the standard substrate for DPP II. The enzyme is a monomer with a
      Mr of 70kDa, pl 5.2, and Km 5.0 microM. Its terminal amino acid sequence was
      XXLLYAIQKRLF and was not identical to that of any known protein. Although
      initially considered to be a DPP II, the enzyme differed in some properties from
      classical DPP IIs. It had a pH optimum of 7.9, was not active on X-pro
      naphthylamides, the usual substrates of mammalian DPP II, but was active on arg
      arg- and asp-arg-naphthylamides, substrates acted on by the DPP III class of
      enzymes. This enzyme therefore combines properties typical of both DPP II and III
      and differs from all previously described DPPs. Activity on lys-ala-beta
      naphthylamide was most abundant during aggregation and its activity is consistent
      with processing specific peptides during development.

PMID- 10204083
TI  - 20S proteasome, hsp90, p97 fusion protein, PA28 activator copurifying oligomers
      and ATPase activities.
AB  - Whether hsp90 acts in an ATP-dependent or independent way is of crucial
      importance for understanding the molecular mechanism of this chaperone and, to
      day, the involvement of ATP hydrolysis in hsp90 function is still a controversial
      subject. ATPase activities may be detected in partially purified hsp90's
      preparations from rabbit muscle. We demonstrate that the major contaminant
      associated with hsp90 is the p97 fusion protein and that these oligomeric
      structures are copurifying together with the 20S proteasome and its PA28
      activator. Improving the purification procedure permits to separate hsp90 and p97
      to homogeneity. Then, our attempts failed to detect any significant ATPase
      activity in the hsp90 fraction. Thus, p97 would be principally responsible for
      the ATPase activity detected in partially purified hsp90 preparations from rabbit
      muscle.

PMID- 10204084
TI  - Pre-conditioning to global cerebral ischemia changes hippocampal
      acetylcholinesterase in the rat.
AB  - This study shows the effect of transient global cerebral ischemia (ISC) on
      hippocampal acetylcholinesterase (AChE) activity. Naive adult Wistar rats
      received either a brief (2 min) or a long (10 min) ischemic episode by the four
      vessel occlusion method. Pre-conditioned rats received double ischemia: a 10 min
      episode inflicted 24 h after a 2 min event, a condition known to confer
      cytoprotection to CA1 pyramidal cells of hippocampus. 2 min of ischemia caused an
      increase in acetylcholinesterase activity both immediately and 30 min after the
      episode, however enzyme activity was significantly decreased after 24 h of
      reperfusion. 10 min of ischemia caused an increase in activity both 60 min and 24
      h after ischemia. Conversely, pre-conditioned rats displayed lower activity both
      immediately and 60 min after ischemia. Our results suggest that: a) neuronal
      death, that follows 10 min of ischemia, is associated to a late increase in
      acetylcholinesterase activity; b) pre-conditioning is related to diminished
      acetylcholinesterase activity. This is in agreement with previous evidence that
      acetylcholinesterase inhibition and maintenance of acetylcholine levels are
      beneficial for cell surviving after cerebral ischemia.

PMID- 10204085
TI  - Identification and purification of proteins from germ cell-conditioned medium
      (GCCM).
AB  - Germ cells are known to regulate Sertoli cell and testicular function possibly
      through released factor(s) or via cell-cell contact. However, the identities of
      many of these putative biological factors are not known. The aim of this study is
      to present a strategy to identify and purify germ cell-derived proteins found in
      germ cell-conditioned medium (GCCM) at a quantity sufficient to permit protein
      microsequencing. The purification scheme of a novel germ cell-derived protein
      from GCCM designated GC-26 is presented along with several germ cell proteins
      using a combination of high pressure liquid chromatography (HPLC) columns. The
      purity of GC-26 and other germ cell proteins were confirmed by sodium dodecyl
      sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE) and silver staining. The
      identities of GC-26, a 26-kDa polypeptide, and other proteins were determined by
      direct protein microsequencing. These partial NH2-terminal amino acid sequences
      were compared with the existing databases at Protein Identification Resource
      (PIR), GenBank, and BLAST. These analyses revealed that these proteins are
      unique. This strategy should be useful for the micropurification of proteins from
      other biological samples and/or fluids.

PMID- 10204086
TI  - Cloning and characterization of the non-catalytic heavy chain of mouse complement
      factor I gene: structure comparison with the human homologue.
AB  - The gene sequence encoding the non-catalytic heavy chain of mouse complement
      factor I (mCFI) was cloned and its exon-intron organization and domain structure
      characterized. The genomic organization of mCFI differs in several aspects from
      its human homologue (hCFI). The intron sizes are remarkably different. Exons 2
      and 4 in mCFI are larger than their counterparts in hCFI by 9 bp and 6 bp
      respectively. Whereas the diversity (D) region of hCFI is encoded by two exons
      (exon 7 or hD2 and exon 8 or hD4), this region in mCFI is encoded by three exons;
      exon 6A or mD1 (located at the 3'-end of the LDLr A2 domain), exon 7 or mD2 and
      exon 8, an extended exon (56 bp) composed of mD3, fused upstream of mD4. In
      contrast, hCFI lacks D1 and D3 subregions and exon 8 in hCFI consists of only
      hD4, 36 bp in length. Thus the heavy chain of mCFI is organized into 10 exons
      compared to 9 exons in hCFI.

PMID- 10204087
TI  - Age-dependent change in arachidonic acid metabolic capacity in rat alveolar
      macrophages.
AB  - Arachidonic acid (AA) metabolism was assessed in cultured alveolar macrophages
      (AM) obtained from newborn (10 days old) and adult (2 months and 4 months old)
      rats. The AMs were stimulated with the calcium ionophore, A23187 (10 microM). The
      released radiolabelled AA metabolites were measured by thin layer chromatography.
      The results showed that among different aged rats, the synthesis of 5
      lipoxygenase (5-LO) metabolites, LTB4, LTC4, LTD4 and 5-HETE were increased with
      age inspite of similar levels of [14C]AA release. In response to A23187, 5-LO
      metabolic capacity of 2 and 4 months old adult rat AMs were increased 21-fold and
      34-fold, respectively, compared with 10 days old rat AMs. As the metabolic
      capacity increased, the release of prostaglandins and thromboxane B2 tended to
      decrease markedly. Newborn rats (10 days old) AM, at the initial developmental
      stage, did not produce a noticeable amount of 5-LO metabolites which,
      conceivably, contribute to high susceptibility of neonatal lung to infection.

PMID- 10204088
TI  - Uptake of vitamin E succinate by the skin, conversion to free vitamin E, and
      transport to internal organs.
AB  - The percent solubility at 34 degrees C (skin temperature) of radioactive
      tocopherol succinate was determined for a number of edible oils, and a
      semisynthetic oil, Myritol 318 (Henkel, Kankakee, IL, a medium chain triglyceride
      prepared from fractionated coconut oil). Its solubility in Myritol 318 was
      approximately 50% better than any of the other oils. 14C-tocopherol succinate was
      diluted (1) into pure Myritol 318, a cosmetic base or (2) 50% tocopherol
      succinate in Myritol 318. These preparations were applied topically to a 2 cm
      diameter circle of the back saddle skin of a hairless mouse (strain skh-1). After
      24 hr, up to 65% of the label was absorbed by the skin and was also found in skin
      removed from areas of the back other than the application area, and internal
      organs such as liver and heart. Up to 6% was hydrolysed to free tocopherol.
      Topical treatment may be an alternative to oral administration in
      gastrointestinal malabsorption diseases.

PMID- 10204089
TI  - Evaluation of kidney and liver subacute toxicity induced by Bezalip-Pravastatin
      Lopid antihyperlipidaemic compounds in rats.
AB  - Renal and hepatic subacute toxicity induced by the antihyperlipidaemic drugs:
      Bezalip-Pravastatin and Lopid was investigated in rats using serum biochemical
      parameters. Toxicological evaluation was performed in serum samples following the
      administration of the therapeutic dose regimens of the compounds that were
      previously shown to be effective in inhibition of 3-hydroxy-methylglutaryl
      coenzyme A (HMG CoA) reductase, the enzyme controlling the rate-limiting step in
      the synthesis of cholesterol, and acyl-CoA cholesterol acyl transferase (ACAT)
      which converts intracellular free cholesterol to cholesterol ester. Renal and
      hepatic subacute toxicity was evaluated by measuring enzyme activity or
      concentrations of: alanine aminotransferace, alkaline phosphatase, aspartate
      aminotransferase, gamma-glutamyltransferase, glucose, potassium, sodium, blood
      urea nitrogen, uric acid and creatinine. The use of the above serum biochemical
      parameters indicated that the overall toxicity impact of antihyperlipidaemic
      drugs was Bezalip = Pravastatin < Lopid. We have found that the Pravastatin--in
      contrast to the above antihyperlipidaemic drugs--only transiently affects the
      biochemical parameters associated with toxicity, but, it affects some of the
      biochemical parameters associated with hepatic and renal toxicity, up to a
      significantly lower extent than the antihyperlipidaemic drugs.

PMID- 10204090
TI  - Glutamate release is involved in PAF-increased cyclic GMP levels in hippocampus.
AB  - The involvement of glutamate in PAF-increased cyclic GMP levels was studied.
      Glutamate treatment caused a dose-response increase of cyclic GMP levels in
      hippocampal slices. The presence of 1 mM glutamate did not modify the effect
      caused by 10(-7)M PAF. To elucidate the involvement of glutamate in this action,
      slices were treated with PAF in the presence of MK-801, a NMDA receptor
      antagonist. Results indicate that PAF-increased cyclic GMP levels were obtained
      by NMDA receptors activation. Finally, results obtained from the experiments
      performed with PAF in the presence of riluzole, to inhibit the glutamate release,
      demonstrated that glutamate release is a stage in the PAF-induced increase of
      cyclic GMP levels in hippocampus.

PMID- 10204091
TI  - Effects of piperine on the lipid composition and enzymes of the pyruvate-malate
      cycle in the testis of the rat in vivo.
AB  - Effects of piperine at two oral doses (5 and 10 mg/kg body weight for 30 days) on
      the lipid composition and some lipogenic enzymes of the rat testis were studied.
      Piperine treatment depleted the total lipid content which was mainly due to the
      diminution of the total phospholipid concentration. All the classes of
      phospholipids were decreased markedly following high dose piperine treatment. In
      contrast, a marked increase in total cholesterol and cholesterol ester was
      evident with a concomitant fall in free cholesterol. A similar trend was found
      for the total glyceride glycerol and its fractions. Total glyceride glycerol and
      triacyl glycerol showed a significant increase at the expense of diacyl glycerol
      in rats treated with the high dose of piperine. Lipogenic enzymes, malate
      dehydrogenase (MDH), malic enzyme (ME) and isocitrate dehydrogenase (ICDH) were
      inhibited by the high dose and only MDH and ME activities were inhibited by the
      low dose treatment.

PMID- 10204092
TI  - Maternal corticotropin-releasing hormone and habituation in the human fetus.
AB  - Elevated concentrations of maternal corticotrophin-releasing hormone (CRH) during
      the 2nd and early 3rd trimester of human pregnancy are associated with
      spontaneous preterm birth, but the effects of maternal CRH on the fetus are
      unknown. Maternal plasma was collected for analysis of CRH concentration, m =
      156.24 +/- 130.91 pg/ml, from 33 pregnant women during Weeks 31-33 of gestation.
      Immediately after collection of plasma, fetal heart rate (FHR) measures were
      obtained in response to a challenge with a series of vibroacoustic stimuli.
      Fetuses of mothers with highly elevated CRH did not respond significantly to the
      presence of a novel stimulus in a repeated series, p = 0.016. These effects on
      the FHR response were not related to parity, fetal gender, medical (antepartum)
      risk, or eventual birth outcomes. Impaired dishabituation in these fetuses of
      mothers with high concentrations of CRH suggests that neurological systems rich
      with CRH receptors that support learning and memory, such as parahippocampal
      regions, may be targets for maternal/placental CRH, with implications for fetal
      neurological development.

PMID- 10204093
TI  - The developmental onset of a rudimentary form of play fighting in C57 mice.
AB  - Play fighting in its most elaborate form involves nonagonistic wrestling between
      pairmates, where one partner grabs, holds, bites, or otherwise contacts the
      other. Such play occurs in the absence of the functional consequences associated
      with serious fighting (e.g., resource acquisition or protection). Typically, the
      biting, nosing, or grooming contact during play fighting is directed at specific
      body targets. House mice have been classified as a species that lacks such play,
      even though play fighting is present in closely related species such as the rat.
      In this study, six litters of C57 mice were observed daily from the week before
      weaning until the week after weaning (15-30 days postnatally). Thirty-min
      videotaped records were collected daily for each litter. Consistent with other
      studies, over 85% of all play involved locomotor play, and most of the social
      play involved noncontact locomotion (86%). However, a rudimentary pattern of the
      "attack and defense" typical of play fighting was found to occur, albeit at a low
      frequency (2% of all play). Most playful attacks involved snout contact with the
      partner's rump, but evidence is provided that suggests that this rump contact may
      be transitory, with the nape area being the primary target for play. Most of the
      playful attacks elicited playful defense (97%), which in all cases involved the
      defender evading such contact by leaping or running away, or by dodging laterally
      away from the attacker. Therefore, there appears to be directed playful attacks
      in this species, with defense limited to evasion. Defensive tactics leading to
      wrestling were never observed. That is, play fighting in mice involves only a
      small subset of what other species, such as rats, exhibit. Nonetheless, the basic
      components of attack and defense are present in mice.

PMID- 10204094
TI  - Indirect dopamine agonists augment the locomotor activating effects of the kappa
      opioid receptor agonist U-50,488 in preweanling rats.
AB  - kappa-Opioid receptor agonists (e.g., enadoline or U-50,488) increase the
      locomotor activity of preweanling rats, while the same drugs depress the
      locomotor activity of adults. Curiously, direct stimulation of dopamine (DA) D2
      like receptors fully attenuates the U-50,488-induced locomotor activity of
      preweanling rats. The purpose of the present study was to determine whether
      indirect DA agonists (i.e., cocaine, methylphenidate, and amphetamine) would also
      attenuate U-50,488's behavioral effects. In two experiments, 17-day-old rats were
      injected with saline or U-50,488 (5 mg/kg, sc) and locomotor activity and
      stereotyped sniffing were assessed. After 20 min, the saline- and U-50,488
      pretreated rats were injected with saline, cocaine (5, 10, or 20 mg/kg, i.p.),
      methylphenidate (10 or 20 mg/kg, i.p.), amphetamine (2.5 or 5 mg/kg, i.p.), or
      the direct D2-like receptor agonist NPA (1 mg/kg, i.p.). As expected, U-50,488
      dramatically enhanced the locomotor activity of 17-day-old rats, while
      attenuating the stereotyped sniffing caused by indirect and direct DA agonists.
      All three indirect DA agonists augmented U-50,488's locomotor activating effects
      across the initial 10 min of testing and then activity declined to U-50,488
      control values. Direct stimulation of DA receptors produced nearly opposite
      effects because NPA attenuated U-50,488-induced locomotor activity across the
      entire testing session. It is uncertain why direct and indirect DA agonists
      affected U-50,488-induced locomotor activity differently, but the relative amount
      of DA D1-like receptor activation is probably not responsible.

PMID- 10204095
TI  - Sonographic structure of isolation-induced ultrasonic calls of rat pups.
AB  - Sonographic analysis of isolation-induced calls of 10- to 17-day-old Sprague
      Dawley rat pups showed that average acoustic parameters of calls changed with
      pups' age. Average call duration increased with age from 80 ms to over 140 ms in
      15-day-old pups. The peak frequency increased from approximately 50 kHz to an
      average of 64 kHz in 17-day-old pups, and the average bandwidth increased from 34
      to 45 kHz in 17-day-old pups. Analysis of the sonographic structure of pup calls
      additionally revealed a tendency to produce two or more alternating sweeps of
      sound frequency in each call. Development of sweeps is the most typical feature
      of pup calls with a dominant call type resembling "U" or inverted "U" shape in
      the sonogram. Number of "U" or inverted "U" call types significantly increased
      with pups' age. It is concluded that pups developed and strengthened those
      acoustic features of distress calls which play a role in intraspecific
      communication and maximize pup survival.

PMID- 10204096
TI  - Prenatal stress suppresses rat pup ultrasonic vocalization and myoclonic
      twitching in response to separation.
AB  - Prenatally stressed infant rats were separated from their dams and littermates on
      postnatal Day 14 and their rates of ultrasonic vocalizations (USVs) and myoclonic
      twitching in response to that separation were recorded. Compared to control pups,
      prenatally stressed pups vocalized significantly less often and showed
      significantly less myoclonic twitching in response to this test. Results are
      interpreted in terms of the ability of prenatal stress to produce infants that
      are behaviorally inhibited when in a novel or stressful situation.

PMID- 10204097
TI  - How the neonatal rat gets to the nipple. II. Changes during development.
AB  - In the course of postnatal development, the motor sequence executed by pups in
      order to attach to the dam's nipple undergoes extensive changes. During the 1st
      postnatal week, the pup performs a rotation along the longitudinal axis of its
      trunk to achieve a supine posture under the mother. The pup then crawls on the
      maternal ventrum while in the supine posture, searching for, finding, and
      attaching to a nipple. During the 2nd postnatal week, this sequence is modified
      and the pup first searches and establishes contact with a nipple before rotating
      to the supine posture. This sequence of movements is then truncated. By postnatal
      Day 11, pups may attach to a nipple while in a prone posture. Developmental
      changes in supination before attaching to the nipple are reminiscent of changes
      in righting during a similar period of development. These observations support
      the idea that both righting and postural adjustments involved in attachment to
      the nipple derive from common motor modules, with righting executed in the
      direction of gravity and rotation to the nipple executed against the force of
      gravity. The parallel structure of these behaviors is consistent with a common
      origin and similar control mechanisms for these distinct motor behaviors that are
      expressed early in postnatal development.

PMID- 10204098
TI  - Prenatal stress reduces the effectiveness of the neurosteroid 3 alpha,5 alpha-THP
      to block kainic-acid-induced seizures.
AB  - The effects of prenatal stress on the ability of the 5 alpha-reduced progesterone
      metabolite and neurosteroid 5 alpha-pregnan-3 alpha-ol-20-one (3 alpha,5 alpha
      THP) to prevent seizures was examined. On gestational Day 18, pregnant rats were
      exposed to 20 min of restraint stress (prenatal stress condition) or no such
      stress (control condition). The adult, gonadectomized offspring exposed to the
      prenatal stress or control condition were administered 0.0, 4.0, or 8.0 mg/kg 3
      alpha,5 alpha-THP 1 hr prior to testing for kainic-acid-induced (32 mg/kg SC)
      ictal activity. The rats exposed to prenatal stress tended to have more partial
      seizures and significantly more tonic clonic seizures that were of longer
      duration than the no prenatal stress rats. Four mg/kg 3 alpha,5 alpha-THP was
      sufficient to significantly reduce seizure duration of no prenatal stress
      females, compared to the 0.0 mg/kg dosage of 3 alpha,5 alpha-THP. Seizure
      duration was reduced in no prenatal stress females by a dose of 4 mg/kg 3 alpha,5
      alpha-THP, whereas a dose of 8 mg/kg was required to obtain comparable seizure
      reduction in prenatally stressed females and males in both groups. There was
      attrition following kainic-acid testing; of the 18 animals in each group
      originally, 9 prenatally stressed males, 6 prenatally stressed females, 6
      nonprenatally stressed males and 5 nonprenatally stressed females were able to be
      tested in the water maze and perfused. One week after seizures, there were no
      differences in the water maze performance of the remaining animals. There were
      fewer cresyl violet-stained neurons in the CA3 region of the hippocampus of
      prenatally stressed rats compared to the nonprenatally stressed rats. Basal
      plasma corticosterone was greater in prenatally stressed animals, but this was
      due to increases in females rather than males. Plasma 3 alpha,5 alpha-THP was not
      significantly different in prenatally stressed males and females compared to
      their no prenatal stress counterparts. These data suggest that the sensitivity
      to, or responsiveness of, 3 alpha,5 alpha-THP to prevent seizures is decreased
      after prenatal stress, particularly in females.

PMID- 10204099
TI  - Diagnostic significance of papillary structures and intranuclear inclusions in
      Hurthle-cell neoplasms of the thyroid.
AB  - Papillary structures and intranuclear inclusions, features which are not
      ordinarily associated with Hurthle-cell lesions, are occasionally noted within
      Hurthle-cell-rich aspirates. The diagnostic significance of these features in
      this setting, if any, is unknown. The purpose of this study was to determine
      whether these features are diagnostically useful. Specifically, since fine-needle
      aspiration cytology cannot distinguish between Hurthle-cell adenoma and
      carcinoma, we wanted to know whether the presence of either feature might aid in
      preoperatively assessing the likelihood of carcinoma vs. adenoma. We identified
      12 cases in which a diagnosis of Hurthle-cell lesion was made by thyroid fine
      needle aspiration biopsy. All cases had subsequent surgery. For every case, all
      cytology slides were reviewed for the presence or absence of papillary structures
      and intranuclear inclusions, after which the findings were correlated with the
      final surgical pathological diagnosis. Seven of the 12 cases had identifiable
      papillary structures, ranging from cases where papillary structures comprised the
      predominant architectural pattern to cases where rare papillary structures were
      found amidst a predominance of sheets and single Hurthle cells. Four of the 12
      cases had intranuclear inclusions. In all cases, intranuclear inclusions were
      uncommon. Of 6 cases that proved to be Hurthle-cell carcinoma, 5 had papillary
      structures on the antecedent fine-needle aspirate cytology, and 2 had
      intranuclear inclusions. Of 6 cases that proved to be Hurthle-cell adenoma, 2 had
      papillary structures, and 2 had intranuclear inclusions. Papillary structures had
      a sensitivity of 83% for the presence of carcinoma, a specificity of 66%, a
      positive predictive value of 71%, and a negative predictive value of 80% (P =
      0.2). Intranuclear inclusions had a sensitivity of 33%, a specificity of 66%, and
      positive and negative predictive values of 50%. Papillary structures are more
      common in Hurthle-cell aspirates than previously recognized. Their presence is
      not diagnostic of carcinoma, but neither does their absence rule out carcinoma.
      However, when found, the likelihood of an ultimate diagnosis of Hurthle-cell
      carcinoma is increased. On the other hand, intranuclear inclusions, when rare,
      appear to have no diagnostic value.

PMID- 10204100
TI  - Fine-needle aspiration biopsy findings in marginal zone B cell lymphoma.
AB  - Marginal zone B cell lymphomas (MZBCLs) represent a category of non-Hodgkin's
      lymphoma which may arise in a wide variety of extranodal organs where they are
      termed low grade B cell lymphomas of mucosa-associated lymphoid tissue (MALT).
      MZBCLs may involve primarily lymph nodes and or spleen where they are designated
      monocytoid B cell lymphoma or splenic marginal zone lymphoma, respectively.
      Recognition of this category of lymphoma, in particular, extranodal MALT
      lymphoma, is clinically significant in determining optimal therapy. Although
      there have been recent case reports describing the cytologic findings in low
      grade MALT lymphoma in various extranodal organs, this category of lymphoma has
      not been widely recognized or discussed in the cytology literature. The cytologic
      findings in seven fine-needle aspirations and two bronchial washings of
      histologically confirmed marginal zone lymphoma (five extranodal MALT lymphomas
      and four nodal marginal zone lymphomas) are described. In all of the cases, the
      cytologic specimens showed a polymorphous proliferation comprising a predominant
      population of intermediate sized lymphoid cells with centrocyte-like or
      monocytoid features, transformed cells, and variable numbers of plasma cells.
      These findings, while highly suggestive of MALT lymphoma in extranodal
      proliferations, may be more difficult to distinguish from reactive conditions in
      lymph nodes.

PMID- 10204101
TI  - Biological behavior and etiology of inflammatory cervical smears.
AB  - Two hundred and fifty-seven consecutive women attending a major maternal and
      child health (MCH) center were studied clinically, colposcopically,
      cytologically, and microbiologically for different gynecologic infections. Out of
      257 cases, 207 (80.5%) had inflammatory cervical smears, of which 183 (88.4%)
      were infected with one or more genital tract infections. Bacterial vaginosis
      (risk, 22.6-fold), chlamydia (risk, 21.6-fold), and human papillomavirus (HPV)
      (risk, 13.5-fold) were independently associated with inflammatory smears. In
      addition, significantly higher proportions of women with inflammatory smears had
      cervical ectopies (28.5% vs. 10.2%) and bleeding ectopies (30.9% vs. 4.1%) as
      compared to noninflammatory smears. Women infected with bacterial/parasitic
      genital infections were given specific treatment. These women were followed up at
      regular intervals to assess the efficacy of antimicrobial therapy. During follow
      up examination, only 26 women (12.6%) showed negative smears. Sixteen women
      developed squamous intraepithelial lesions (SIL) during follow-up, and 163 women
      had persistent inflammatory smears. Multivariate analysis revealed that
      persistent inflammatory smears were associated with herpes simplex virus (HSV)
      infection, as revealed through detection of IgA antibodies to HSV (risk, 11.5
      fold). Progression of SIL was associated with HPV infection (risk, 17.6 fold).
      Thus, inflammatory smears are associated with different types of infection, most
      of which do not respond to antimicrobial therapy.

PMID- 10204102
TI  - Distribution of calponin and smooth muscle myosin heavy chain in fine-needle
      aspiration biopsies of the breast.
AB  - The cell types that may be present in any fine-needle aspiration biopsy (FNAB) of
      breast include epithelial cells (EC), myoepithelial cells (MEC), bipolar stromal
      cells (BSC), vascular pericytes/endothelial cells (VPEC), and adipose cells (AC).
      The recognition of most of these benign cellular elements in aspirates of the
      breast is relatively straightforward, based on distinct cytomorphologic criteria.
      However, there is controversy regarding the recognition of MEC because BSC are
      often referred to as MEC by cytopathologists. It is important to identify MEC in
      breast aspirates, because their presence has been associated with benign
      epithelial proliferations. In this study we used immunocytochemical methods on
      archival cytology slides with antibodies specific for MEC, calponin, and smooth
      muscle myosin heavy chain (SMMHC), to determine the distribution of MEC in FNAB
      of the breast and to ascertain the distribution of MEC in in situ and invasive
      carcinomas. Fifteen benign FNABS of breast and corresponding tissue biopsies were
      obtained along with 10 malignant FNABS and corresponding excisional breast
      biopsies from 1989-1993. Calponin and SMMHC antibodies were used on archival
      alcohol-fixed Papanicolaou-stained direct smears as well as the corresponding
      tissue sections. The distribution and pattern of positive immunostaining with
      both antibodies were recorded on the benign elements and the carcinomas for both
      cytologic and histologic slides. Benign breast tissues demonstrated strong
      continuous immunostaining for calponin and SMMHC of MEC. The interlobular stromal
      cells as well as intralobular stromal cells showed no immunostaining with either
      antibody. In cytologic preparations, MEC staining with calponin and SMMHC
      appeared as spindle cells between epithelial cells or along the edges of the
      epithelial groups. The bipolar stromal cells did not stain with either antibody.
      The tissues with DCIS (ductal carcinoma in situ) often showed the presence of MEC
      with strong calponin immunostaining, but sometimes the immunostaining was
      discontinuous or entirely absent around markedly dilated ducts. The SMMHC
      antibody was invariably negative, with architectural DCIS in dilated ducts. Two
      cases of DCIS with prominent periductal fibrosis or inflammation were positive
      for calponin, but the periductal stromal cells were calponin- and SMMHC-negative.
      Invasive carcinoma was negative for both calponin and SMMHC, but areas of DCIS
      were often positive in a discontinuous pattern. In conclusion, 1) Benign cellular
      elements from breast tissue FNAB showed strong continuous decoration of MEC with
      both calponin and SMMHC. Vascular pericytes and vascular smooth muscle were
      positive for both antibodies, but these cells were not observed in the FNAB.
      Benign proliferative epithelium showed no local increase in MEC with either
      antibody. Bipolar stromal cells in tissue and smears did not stain for MEC
      antibodies. 2) BSC did not correspond morphologically to MEC, and were not
      decorated with calponin or SMMHC. 3) Calponin-positive MEC were commonly
      associated with in situ ductal lesions, although they may at times have been
      discontinuous or absent entirely. DCIS may be recognized in FNAB by the presence
      of calponin-positive MEC associated with tumor cell groups. 4) Invasive
      carcinomas were invariably negative for MEC with these antibodies.

PMID- 10204103
TI  - Cytological clues of bone marrow findings in Kala-Azar.
AB  - A case-control study was done on 77 cases in divided groups in order to test the
      sensitivity and specificity of new diagnostic morphologic criteria for visceral
      leishmaniasis. We found cytological findings other rather than the presence of
      intracytoplasmic Leishman Donovan bodies, i.e., the following interrelated items:
      1) hypolymphopoiesis; 2) dyserythropoiesis; 3) blebbing of the granulocytic
      series and exfoliation of the blebs as "granular stippling;" and 4) various-sized
      damaged of the activated macrophages to apoptotic ones and cytoplasmic blebbing
      of the parasitophorous vacuoles and exfoliation of them as empty "basophilic bare
      cells." These two latter findings were based on our own observations over the
      past few years. Statistical analysis showed that these new criteria have more
      efficacy in diagnosis than previous ones; the differences were statistically
      significant. Findings obtained from this study could increase the values of
      diagnostic histopathological methods for detecting visceral leishmaniasis.

PMID- 10204104
TI  - Cytologic score and DNA-image analysis in the classification of borderline breast
      lesions: a prospective study on 47 fine-needle aspirates.
AB  - We prospectively evaluated the accuracy of the cytologic score system developed
      by Masood et al. combined with DNA-image analysis in the subclassification of 47
      fine-needle aspiration samples with cytologic features of borderline breast
      lesions. Cytologic scores ranged between 12-18. All cases underwent surgical
      excision of the lesion, and histology revealed 24 cases of florid hyperplasia, 8
      of atypical hyperplasia, and 11 noninvasive and 4 invasive ductal carcinomas. DNA
      image analysis demonstrated 33 diploid and 14 aneuploid cases. Diploid samples
      were divided into slowly proliferating (S + G2/M < or = 13%) and rapidly
      proliferating (S + G2/M > 13%) cases. By considering florid hyperplasia a "low
      risk" lesion and by amalgamating atypical hyperplasia, and in situ and invasive
      ductal carcinoma in the category of "high-risk" lesions, the positive predictive
      value of a score value > 16 was 100%. In cases scoring < or = 16, the slowly
      proliferating pattern had a negative predictive value of 95%, while the aneuploid
      and rapidly proliferating patterns had a positive predictive value of 100% and
      63%, respectively. We conclude that a combination of cytologic score evaluation
      and DNA-image analysis is very useful in differentiating "low-risk" from "high
      risk" cases in the field of breast borderline lesions, thus improving the impact
      of fine-needle aspiration diagnosis on patient management.

PMID- 10204105
TI  - Cerebral spinal fluid involvement by Hodgkin's disease diagnosed by CSF cytology
      and immunocytochemistry.
AB  - A 39-yr-old man with stage IV Hodgkin's disease (HD) involving bone marrow was
      being evaluated for autologous bone marrow transplantation when he developed
      diplopia, prompting a lumbar puncture tap for cerebral spinal fluid (CSF)
      examination. Cytologic examination of the CSF revealed numerous Reed-Sternberg
      (RS) cells in a polymorphous inflammatory background of small lymphocytes,
      monocytes, rare plasma cells, and eosinophils. However, magnetic resonance
      imaging (MRI) studies of the brain and spinal cord failed to reveal evidence of
      leptomeningeal disease or intracranial masses. Repeat CSF examination again
      demonstrated cytologic evidence of HD. Immunocytochemical stains established that
      the RS cells and mononuclear Hodgkin's cells were positive for CD30 and CD20 but
      negative for CD15; this phenotype was identical to that of RS cells in the
      initial diagnostic bone marrow biopsy, confirming CSF involvement by HD. The
      patient was treated with intrathecal methotrexate, 15 mg, 6 days after his bone
      marrow transplant. After treatment, all subsequent CSF cytology specimens were
      negative for tumor. In this case of disseminated HD, cytologic examination
      allowed for early detection of CNS involvement by lymphoma prior to development
      of radiographically detectable lesions.

PMID- 10204106
TI  - Fine-needle aspiration cytology of a mediastinal seminoma associated with
      multilocular thymic cyst.
AB  - Multiloculated thymic cysts are uncommon lesions that can be either acquired or
      associated with malignancies. This report describes the fine-needle aspiration
      (FNA) cytology of a mediastinal seminoma with prominent cystic change, confirmed
      by surgical pathology examination and ancillary studies performed on both the
      cytology and tissue specimens. The FNA cytology revealed clusters of malignant
      oval-to-polygonal-shaped cells with large oval nuclei possessing prominent
      nucleoli set in a pale-to-eosinophilic cytoplasm. These cells were surrounded by
      a dense lymphoid infiltrate along with a few noncaseating granulomas. The large
      malignant seminoma cells stained positive for placental alkaline phosphatase
      (PLAP) and negative for both low molecular and broad-spectrum cytokeratin. The
      differential diagnosis of malignancies associated with thymic cysts is presented.
      To the best of our knowledge, this is the first report of aspiration cytology of
      a mediastinal seminoma associated with a multilocular cyst.

PMID- 10204107
TI  - Fine-needle aspiration cytology of well-differentiated inflammatory liposarcoma:
      a case report with histologic follow-up.
AB  - Inflammatory liposarcoma is an unusual variant of well-differentiated
      liposarcoma. We report on the fine-needle aspiration (FNA) cytology findings of a
      retroperitoneal well-differentiated inflammatory liposarcoma from a 63-yr-old
      white female. The smears showed numerous dispersed inflammatory cells, with the
      majority being reactive lymphoid cells and plasma cells. There were scattered,
      large, atypical cells containing multiple or hyperlobated nuclei with coarse
      chromatin and abundant ill-defined cytoplasm. The large atypical cells, as well
      as the inflammatory cells, were also found within the fibrous tissue fragments.
      The follow-up surgical resection of the tumor demonstrated a well-differentiated
      inflammatory liposarcoma with coexistent dedifferentiated areas and lipoma-like,
      well-differentiated liposarcoma. With the appropriate anatomic and radiographic
      settings, the FNA cytology findings of abundant, reactive inflammatory cells and
      scattered, large, atypical tumor cells that are CD15-, CD30-, and cytokeratin
      negative are highly suggestive of a well-differentiated inflammatory liposarcoma.

PMID- 10204108
TI  - Spermatocytic seminoma: a cytology and histology case report with review of the
      literature.
AB  - Fine-needle aspiration cytology (FNAC) findings are described in a case of
      spermatocytic seminoma occurring in a 52-yr-old male, involving the left testis.
      The smears showed three populations of cells (small, medium, and large), with a
      preponderance of medium-sized cells showing visible nucleoli. The background was
      clean, in contrast to the "tigroid" substance seen in classical seminoma. Low
      mitotic rate and absence of lymphocytes were the other features helpful in
      diagnosis. Because of these distinct morphological features, a preoperative
      diagnosis of spermatocytic seminoma was possible, with subsequent confirmation on
      histopathology. The case is being reported because of the rarity of this tumor,
      and because there have been only a few reported cases of FNAC diagnosis.

PMID- 10204109
TI  - Cytomorphologic appearance of follicular dendritic-cell tumor: a case report.
AB  - Follicular dendritic-cell (FDC) tumors are extremely rare, recently described
      neoplasms. Only one report currently exists in the cytology literature. We
      present a case of FDC tumor with emphasis on its cytomorphology and its
      correlation with histology, immunohistochemistry, and ultrastructure.

PMID- 10204110
TI  - Malignant phyllodes tumor with chondrosarcomatous differentiation: report of a
      case with cytological presentation.
AB  - Malignant phyllodes tumor is a rare breast tumor with neoplastic epithelial and
      stromal components. The stromal component may show homologous and heterologous
      sarcomatous elements, including chondrosarcomatous and osteosarcomatous
      differentiation. Because these tumors may present with an almost exclusively
      sarcomatous component, it is important for the pathologist to include this entity
      in the diagnostic considerations of fine-needle aspirations of breast neoplasms
      showing sarcomatous differentiation. Following surgical excision, careful
      examination of the gross specimen and thorough sampling of the specimen is
      recommended before rendering a definitive histologic diagnosis. We describe the
      cytologic and histologic findings in a case of malignant phyllodes tumor with
      sarcomatous overgrowth showing predominantly chondrosarcomatous differentiation.

PMID- 10204111
TI  - Natural killer cell lymphoma of the small intestine: diagnosis by flow cytometric
      immunophenotyping of paracentesis fluid.
AB  - Natural killer (NK) cell lymphoma is a mass-forming neoplasm of putative NK cell
      lineage that typically appears in extranodal locations and has the following
      immunophenotype: CD2 positive, surface CD3 negative, cytoplasmic CD3 positive,
      and CD56 positive. We report a case of small-intestinal NK cell lymphoma that was
      originally diagnosed as an enteropathy-associated T-cell lymphoma based on
      paraffin immunohistochemistry. However, subsequent flow cytometric
      immunophenotyping of paracentesis fluid resulted in the correct diagnosis. We
      describe the case to illustrate the usefulness of this technique, which has not
      previously been described in such a case.

PMID- 10204112
TI  - Cytokeratin positivity in fine-needle aspirates of metastatic malignant melanoma:
      fact or fiction?

PMID- 10204113
TI  - Air bubbles on Papanicolaou smears mimicking adipose tissue.

PMID- 10204114
TI  - Molecular biology of adenosine triphosphate-sensitive potassium channels.
AB  - KATP channels are a newly defined class of potassium channels based on the
      physical association of an ABC protein, the sulfonylurea receptor, and a K+
      inward rectifier subunit. The beta-cell KATP channel is composed of SUR1, the
      high-affinity sulfonylurea receptor with multiple TMDs and two NBFs, and KIR6.2,
      a weak inward rectifier, in a 1:1 stoichiometry. The pore of the channel is
      formed by KIR6.2 in a tetrameric arrangement; the overall stoichiometry of active
      channels is (SUR1/KIR6.2)4. The two subunits form a tightly integrated whole.
      KIR6.2 can be expressed in the plasma membrane either by deletion of an ER
      retention signal at its C-terminal end or by high-level expression to overwhelm
      the retention mechanism. The single-channel conductance of the homomeric KIR6.2
      channels is equivalent to SUR/KIR6.2 channels, but they differ in all other
      respects, including bursting behavior, pharmacological properties, sensitivity to
      ATP and ADP, and trafficking to the plasma membrane. Coexpression with SUR
      restores the normal channel properties. The key role KATP channel play in the
      regulation of insulin secretion in response to changes in glucose metabolism is
      underscored by the finding that a recessive form of persistent hyperinsulinemic
      hypoglycemia of infancy (PHHI) is caused by mutations in KATP channel subunits
      that result in the loss of channel activity. KATP channels set the resting
      membrane potential of beta-cells, and their loss results in a constitutive
      depolarization that allows voltage-gated Ca2+ channels to open spontaneously,
      increasing the cytosolic Ca2+ levels enough to trigger continuous release of
      insulin. The loss of KATP channels, in effect, uncouples the electrical activity
      of beta-cells from their metabolic activity. PHHI mutations have been informative
      on the function of SUR1 and regulation of KATP channels by adenine nucleotides.
      The results indicate that SUR1 is important in sensing nucleotide changes, as
      implied by its sequence similarity to other ABC proteins, in addition to being
      the drug sensor. An unexpected finding is that the inhibitory action of ATP
      appears to be through a site located on KIR6.2, whose affinity for ATP is
      modified by SUR1. A PHHI mutation, G1479R, in the second NBF of SUR1 forms active
      KATP channels that respond normally to ATP, but fail to activate with MgADP. The
      result implies that ATP tonically inhibits KATP channels, but that the ADP level
      in a fasting beta-cell antagonizes this inhibition. Decreases in the ADP level as
      glucose is metabolized result in KATP channel closure. Although KATP channels are
      the target for sulfonylureas used in the treatment of NIDDM, the available data
      suggest that the identified KATP channel mutations do not play a major role in
      diabetes. Understanding how KATP channels fit into the overall scheme of glucose
      homeostasis, on the other hand, promises insight into diabetes and other
      disorders of glucose metabolism, while understanding the structure and regulation
      of these channels offers potential for development of novel compounds to regulate
      cellular electrical activity.

PMID- 10204115
TI  - The molecular pathogenesis of corticotroph tumors.

PMID- 10204116
TI  - The vitamin D receptor and the syndrome of hereditary 1,25-dihydroxyvitamin D
      resistant rickets.

PMID- 10204117
TI  - The connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed
      (CCN) family.

PMID- 10204118
TI  - The cadherin-catenin system: implications for growth and differentiation of
      endocrine tissues.
AB  - Cell-cell adhesion, as mediated by the cadherin-catenin system, is a prerequisite
      for normal cell function and the preservation of tissue integrity. With recent
      progress in our understanding, beta-catenin as a component of a complex signal
      transduction pathway may serve as a common switch in central processes that
      regulate cellular differentiation and growth. The function of the cadherin
      catenin system in cell adhesion as well as in intracellular signaling, appears to
      be subjected to multifactorial control by a variety of different mechanisms, and
      data on a hormonal control of these signaling pathways, even though scarce to
      date, suggest an important regulatory influence in many cellular systems. Loss of
      E-cadherin-catenin function was described in many tumors along with an increased
      invasiveness and a decreased prognosis of many carcinomas, including tumors of
      endocrine glands and their target systems, and a causal role of this loss-of
      function in the multifactorial process of tumorigenesis was recently proven in
      genetic mouse models. Modification of E-caderin-catenin function in endocrine and
      nonendocrine tumors may involve germline and somatic gene mutations, epigenetic
      mechanisms such as gene silencing due to promotor-hypermethylation, and
      posttranscriptional events, likely to be involved in many endocrine tissues and
      their target organs. Such events may converge on nuclear activation of oncogenes
      such as c-myc by the beta-catenin/TCF4 complex. The expression and functional
      status of the components of the cadherin-catenin system may serve as prognostic
      markers for endocrine and nonendocrine tumors. The frequent involvement of
      functional dysregulation in many tumors raises hopes that better definition of
      the regulation of all components of the cadherin-catenin system and their
      response to extracellular modulators may eventually lead to new therapeutic
      approaches for these tumors and help to prevent, more specifically, growth,
      invasion, and metastasis of these carcinomas.

PMID- 10204119
TI  - All Wales surveillance of methicillin-resistant Staphylococcus aureus (MRSA): the
      first year's results.
AB  - Over the last five years, hospitals in Wales have experienced difficulties with
      increasing numbers of isolates of methicillin-resistant Staphylococcus aureus
      (MRSA). Continuous total population surveillance of MRSA was introduced with the
      objectives of gaining an understanding of the extent and variation in time and
      place of its occurrence, the burden of disease and possible risk factors
      associated with its isolation and resistance to other antibiotics. All first
      isolates of MRSA from both hospital and community settings and all isolates of
      methicillin-sensitive Staphylococcus aureus (MSSA) associated with bacteraemia
      and cerebrospinal fluid (CSF) isolates detected in medical microbiology
      laboratories in Wales were collected via CoSurv, a set of interconnected data
      base modules for communicable disease control. A data set was collected on each
      isolate and the patient associated with that isolate and compiled centrally at
      CDSC (Wales) for all-Wales analysis of the MRSA situation. Surveillance started
      in January 1996 and at the end of the first year, 2700 new isolates of MRSA had
      been reported from hospital and community settings, giving a rate of
      92.43/100,000 population. The incidence of MRSA from bacteraemias and CSF was
      5.20/100,000 compared with 12.70/100,000 for MSSA. MRSA from bacteraemia and CSF
      was significantly more commonly associated with male patients than MSSA. MRSA
      patients were significantly older. For all MRSA isolates, the highest reporting
      rate was in men aged 75+ (647.21/100,000). The highest incidence of invasive
      disease was also in men aged 75+ (45.69/100,000). Isolates from post-surgical
      patients were more likely to be involved in invasive disease (OR = 2.59), P <
      0.001) than strains from other sources. The majority of isolates were resistant
      to at least two antibiotics in addition to methicillin, most frequently
      erythromycin and the fluoroquinolones. Very little resistance to fusidic acid,
      mupirocin or rifampicin was reported. Continuous total population surveillance
      has provided a minimum incidence of MRSA in Wales and has allowed a simple and
      intelligible picture of the problem to be determined, which has been fed back to
      hospitals to assist decisions on control.

PMID- 10204120
TI  - Invasive yeast infections other than Candida spp. in acute leukaemia.
AB  - During the last two decades, the treatment of leukaemia has changed
      significantly; increasing intensity of chemotherapy and bone marrow
      transplantation have lead to profound immunosuppression, prolonged stays in
      hospital, vascular catheterization, administration of broad spectrum
      antimicrobial agents and extensive use of prophylactic antifungal drugs. All but
      the last of these risk factors have increased the incidence of fungal infections
      in leukaemic patients and have significantly changed the spectrum of pathogens in
      favour of non-Candida species. In major haematological centres in Europe and the
      US, the proportion of non-Candida yeast isolated from patients increased from 1
      to 5% in 1980 to 10 to 25% after 1990. However, there are not enough data to
      assess whether mortality due to these species is higher than that due to Candida
      spp. (30-40%) or filamentous fungi (50-70%). In this article, specific risk
      factors and therapeutic outcome of yeast infections other than Candida spp. in
      leukaemia such as Malassezia furfur, Trichosporon spp., Blastoschizomyces
      capitatus, Rhodotorula rubra, Saccharomyces cerevisiae, Clavispora lusitaniae,
      Cryptococcus laurentii and Hansenula anomala are reviewed. An analysis of risk
      factors from the National Cancer Institute, Bratislava has shown that non-Candida
      yeast infections (N = 15) in cancer patients are associated with leukaemia and
      neutropenia (P = < 0.002, 0.005), more often fatal than those caused by C.
      albicans (N = 51) (P < 0.006) but not non-albicans Candida (N = 34) and are
      associated with quinolone (P < 0.0001) and itraconazole prophylaxis (P < or =
      0.05, 0.015) compared to both C. albicans or non-albicans Candida respectively.

PMID- 10204121
TI  - Comparative efficiency of nitrocellulose membranes versus RODAC plates in
      microbial sampling on surfaces.
AB  - The efficiency of nitrocelluose membranes in collecting microbial samples from
      rigid and flat surfaces has been studied and compared with that of RODAC plates.
      The experimental design was based on multiple samplings in close succession in
      the same place. The median efficiency of membrane filters (78.55) was higher than
      that of RODAC plates (65.37). The data demonstrate the reliability of membranes
      and show that membranes are more efficient than RODAC plates as a sampling method
      for measuring surface microbial contamination.

PMID- 10204122
TI  - Nosocomial infection, indices of intrinsic infection risk, and in-hospital
      mortality in general surgery.
AB  - The objectives of this paper are to assess whether two indices of intrinsic
      infection risk (the SENIC and the NNIS index) predict in-hospital mortality and
      the attributable in-hospital mortality due to nosocomial infection in surgical
      patients. A prospective study on 4714 patients admitted to three hospitals has
      been carried out. The relative risk and its 95% confidence interval (CI) were
      estimated. Multiple-risk factors adjusted for odds ratios (OR) were yielded by
      logistic regression analysis. Overall, 119 patients (2.5%) died before hospital
      discharge. Both the SENIC and the NNIS indices were related to in-hospital
      mortality in crude data. After controlling for several variables (age, sex, ASA
      score, cancer, renal failure, diabetes mellitus, stay at the ICU), the SENIC
      index did not show any significant trend with mortality (P = 0.252), whereas the
      trend was significant for the NNIS index (P < 0.001). Risk of death in patients
      with one nosocomial infection was 7.5%, and in patients developing more than one
      nosocomial infection was 17.1%. After adjusting for several confounding
      variables, the development of an organ/space surgical site infection was
      significantly related to mortality (OR = 4.5, 95% CI 1.5-15.6) as was blood
      infection (OR = 17.3, 95% CI 3.5-87.0). The association of a surgical site
      infection and either a respiratory tract infection or a blood infection also
      increased significantly the risk of in-hospital mortality (OR = 3.3, 95% CI 1.2
      8.7). In conclusion, the NNIS index is a good predictor of in-hospital mortality.
      Patients developing an organ/space surgical site infection and/or a blood
      infection have an increased risk of in-hospital mortality.

PMID- 10204123
TI  - Clostridium difficile: an update on its epidemiology and role in hospital
      outbreaks in England and Wales.
AB  - Data from the surveillance system of general outbreaks of infectious intestinal
      disease and from laboratory reports collated by the Communicable Disease
      Surveillance Centre (CDSC) and requests for outbreak investigation by the PHLS
      Anaerobe Reference Unit were used to evaluate the current epidemiology of
      Clostridium difficile infection in England and Wales. Between January 1992 and
      December 1996, CDSC received 10,220 laboratory reports of C difficile isolation
      from patient's faeces and 26,873 of toxin in faeces. Over 75% of all reports were
      of people aged 64 years and over. The surveillance system captured a minimum data
      set on 694 hospital outbreaks of infectious intestinal disease. C. difficile was
      responsible for 109 (15%) outbreaks affecting 1625 people, of whom 1152 were
      found to have a C. difficile toxin producing strain. The median duration of
      outbreaks was 11 days. Fingerprinting by Pyrolysis Mass Spectrometry (PMS) was
      performed by the PHLS Anaerobe Reference Unit in 60 outbreaks, and typing by
      Polymerase Chain Reaction ribotyping (PCR) in 14.

PMID- 10204124
TI  - Serratia marcescens pseudobacteraemia in neonates associated with a contaminated
      blood glucose/lactate analyzer confirmed by molecular typing.
AB  - Three episodes of Serratia marcescens pseudobacteraemia occurred on a neonatal
      intensive care unit. Following the first two cases, one full term and one pre
      term infant, the source was identified as a glucose/lactate analyzer. Blood
      culture and environmental isolates of the organisms involved were
      indistinguishable when subjected to pulsed-field gel electrophoresis of Spe 1
      digests and PCR ribotyping. Failure to recognize pseudobacteraemia in neonates
      results in inappropriate therapy for the individual and increased antibiotic
      pressures on the unit. Attention to the possibility of cross infection when using
      automated analyzers is required to minimize the risks of true or pseudoinfection
      to patients.

PMID- 10204125
TI  - Outcome following haemodialysis catheter-related Staphylococcus aureus
      bacteraemia.
AB  - Staphylococcus aureus is a frequent cause of haemodialysis access-related
      bacteraemia. The propensity for this organism to seed from the bloodstream to
      distant sites is well recognized, but the rate at which this occurs is poorly
      defined in patients with removable haemodialysis catheters. This retrospective
      study identified 47 patients with 50 episodes of S. aureus haemodialysis catheter
      related bacteraemia between August 1993 and December 1995. Adverse events were
      recorded until February 1996. Thirty of 50 episodes (60%) were apparently
      uncomplicated. Bacterial seeding to heart valves or distant sites was documented
      in eight episodes (16%), of which six occurred during antibiotic therapy. A
      further 12 patients had persistent bacteraemia in the absence of a defined focus
      of infection, the last positive blood culture ranging from 2-19 days (mean 6.6,
      median 5) after removal of the haemodialysis catheter and commencing appropriate
      antibiotic treatment. The serious nature of this infection confirms the need for
      prevention, together with effective strategies for investigation and treatment in
      this patient population.

PMID- 10204126
TI  - An audit of first generation cephalosporin usage.
AB  - Cefadroxil is a semi-synthetic first generation oral cephalosporin with
      advantages of almost 100% excretion in the urine within six hours and low cost.
      It was freely available in the formulary and we undertook an audit of its usage,
      the indications cited, underlying clinical conditions and relevant microbiology
      in 106 cases. Following the audit, cefadroxil was restricted, available only on
      the advice of a microbiologist. Subsequently, another survey was carried out to
      document the reasons for requesting cefadroxil by clinical staff and the
      alternatives suggested in each case. The first survey revealed that in 91% cases,
      cefadroxil had been used inappropriately. The second suggested that the reasons
      for requesting it were based upon misunderstanding by clinicians as to its value.
      The only useful indication identified was the treatment of susceptible bacteruria
      in pregnancy. A suitable oral alternative could be identified for all other cases
      where an antibiotic was indicated. We believe that first generation
      cephalosporins such as cefadroxil have little role in hospital practice and
      should therefore be restricted.

PMID- 10204127
TI  - A comparison of teicoplanin versus cephradine plus metronidazole in the
      prophylaxis of post-operative infection in vascular surgery.
AB  - A total of 272 patients were enrolled into this prospective, unblinded,
      randomized comparison of single-dose teicoplanin vs three doses of cephradine
      plus metronidazole as prophylaxis for vascular surgery at St James's and Seacroft
      Hospitals, Leeds, UK. In all, 71.3% of patients (194/272) were enrolled at St
      James's University Hospital. Patients received either a single dose of
      teicoplanin, 6 mg/kg i.v., or cephradine, 1 g i.v. with metronidazole, 1 g
      rectally, at induction of anaesthesia followed by two further 1 g doses of
      cephradine and metronidazole 8 and 16 hours later. There were 136 patients in
      each treatment group. The most common operations were femoropopliteal grafts (96)
      and aortic aneurysm repairs (47). In the 'intention-to-treat' analysis, primary
      wound infections were seen in 4.4% of patients (6/136) receiving teicoplanin and
      5.9% of patients (8/136) receiving cephradine plus metronidazole (95% CI -6.7%,
      +3.8%). Other disturbances to wound healing occurred in 23 patients (11 in the
      teicoplanin and 12 in the cephradine plus metronidazole group). Secondary
      respiratory tract infections occurred in 17 patients (8 receiving teicoplanin and
      9 receiving cephradine plus metronidazole). In the evaluable patients analysis,
      primary wound infections occurred in 3.5% of patients (4/114) receiving
      teicoplanin and 5.1% of patients (6/117) receiving cephradine plus metronidazole.
      Staphylococcus aureus and Proteus sp. were the most common pathogens in primary
      wound infections. Despite the absence of Gram-negative cover in the teicoplanin
      group, Gram-negative infections occurred more often in the cephradine plus
      metronidazole group. Surgery of the lower extremities carried the highest risk of
      post-operative infection. Rates of infection were significantly higher at
      Seacroft Hospital (P = 0.001), and significantly higher for cephradine plus
      metronidazole between the two hospitals (P = 0.0008). Adverse events occurred in
      40 patients receiving teicoplanin (29.4%) and 39 patients receiving cephradine
      plus metronidazole (28.7%). In 19 patients receiving teicoplanin (14%) and 15
      receiving cephradine plus metronidazole (11%) these events were considered to be
      related to the study drugs. The most often reported events were infections,
      cardiac events and vascular phenomena (haematoma or emboli). Marked changes in
      haematological parameters and liver function tests were noted seven days after
      operation in patients in each treatment group, but these resolved quickly as the
      effects of the operation subsided. ESR remained elevated in both groups at the
      six-month follow-up assessment. It is concluded from this two-centre study that a
      single dose of teicoplanin shows similar efficacy to a three-dose regimen of
      cephradine plus metronidazole as prophylaxis for wound infection in vascular
      surgery. Both regimens were well tolerated, and there was an equal incidence of
      adverse events in the two regimens, which reflected the poor general health
      status of this elderly study population.

PMID- 10204128
TI  - Ten-year follow-up study of hepatitis B virus infection and vaccination status in
      hospital employees.
AB  - We sought to determine the incidence of infection with hepatitis B virus (HBV)
      amongst hospital employees over a 10-year period and to assess the extent and
      efficacy of vaccination against HBV in this population. In 1984 a cohort of 301
      hospital employees was tested for hepatitis B surface antibody (anti HBs),
      hepatitis B core antibody (anti HBc), and hepatitis B surface antigen (HBsAg).
      Ten years later, 160 (53%) of these workers remained at the hospital and were re
      tested. In addition, they were tested for hepatitis C virus antibody (anti HCV).
      Records of the hospital vaccination program were inspected to determine the rate
      and effectiveness of vaccination in these workers. Over the ten year period two
      of the 160 retested workers (1.25%) had sero-converted to anti HBc positive,
      yielding an incidence density of 0.27 cases per 100 person-years exposed in
      unvaccinated workers. While the overall seroprevalence of anti HBc did not change
      significantly between 1984 (81/301, 27%) and 1994 (39/160, 24%), it was much
      greater than that of the general population (10%). A significantly greater
      percentage of Jews of Sephardi ancestry (22/65, 34%) were positive for anti HBc
      than those of Ashkenazi ancestry (15/90, 17%, P < 0.05). In addition, doctors
      were found to be less likely to be anti HBc positive than nurses (4% vs. 25%,
      respectively, P < 0.01). Two cases of anti HCV positivity were discovered
      yielding a prevalence of 1.25% in the 1994 cohort as compared to 0.15% in the
      population of healthy blood donors. Of the 93 employees of the 1994 cohort
      eligible for vaccination (i.e., anti HBc-negative and employed in an occupation
      involving potential exposure to HBV), 53 (57%) had received vaccination and
      showed protective antibody titers (anti HBs > or = 10 i.u./ml). 17/52 workers
      with documented vaccinations (33%) did not have detectable antibody levels one to
      eight years after vaccination. In conclusion, the seroprevalence of anti HBc and
      anti HCV is significantly higher in this cohort of hospital employees than in the
      general population. The relatively low vaccination rate among at-risk personnel
      emphasizes the need for more effective vaccination programs.

PMID- 10204129
TI  - Controlling MRSA.

PMID- 10204130
TI  - Black pigmented fungi in water.

PMID- 10204131
TI  - The timing of surgical alignment for congenital (infantile) esotropia.
AB  - At this time, the beneficial effect of accurate alignment by age 2 in congenital
      esotropia has been well established by clinical and laboratory studies. There is,
      however, only scanty clinical evidence that alignment before age 1, much less
      before 6 months of age, may yield a better quality of binocularity (i.e., refined
      stereoacuity) than alignment by age 2. Pitfalls of very early alignment are
      present. In addition, the ophthalmologist must be vigilant in following the
      initially aligned patient and be ready to treat vertical motor defects,
      amblyopia, and acquired refractive errors. The need for additional horizontal
      surgery after initial alignment is also common. The optimum result in the
      surgical treatment of congenital esotropia generally shows binocularity that is
      within the confines of a monofixation syndrome, and refined stereoacuity remains
      an elusive target and a rare outcome, no matter at what age the alignment is
      achieved.

PMID- 10204133
TI  - Unilateral or asymmetric congenital ptosis, head posturing, and amblyopia.
AB  - PURPOSE: To determine the prognostic implication of compensatory head posturing
      in patients with unilateral or asymmetric congenital ptosis. METHODS: A
      retrospective review of 80 consecutive patients with unilateral or asymmetric
      congenital ptosis was performed. The presence of documented compensatory head
      posturing, age of onset, age of presentation, visual acuity, refraction, and
      amblyopia were recorded, and binocularity was tested. RESULTS: Five of seven
      (71%), patients with unilateral or asymmetric congenital ptosis and compensatory
      head posturing had amblyopia. All of these patients had straight eyes and four of
      the five amblyopic patients had anisometropia of less than 2 diopters (D).
      CONCLUSION: The high incidence of amblyopia in this group can occur in the
      absence of significant anisometropia and strabismus. This unusually high
      incidence of amblyopia in this subgroup of patients with unilateral or asymmetric
      congenital ptosis and compensatory head posturing warrants compulsive examination
      and prophylactic part-time occlusion therapy of the nonptotic eye until reliable
      vision testing can be performed.

PMID- 10204132
TI  - Early-onset accommodative esotropia.
AB  - PURPOSE: To determine the frequency of accommodative esotropia with onset by 6
      months of age; to determine if the presence or absence of characteristics usually
      associated with infantile esotropia can help in the diagnosis; and to determine
      if antiaccommodative therapy is adequate treatment for the esotropia. METHODS:
      The charts of 100 patients with infantile esotropia, seen over a 2-year period
      (September 1995 to September 1997), were reviewed. We identified those with at
      least 2.25 diopters (D) of hyperopia and determined the presence of large angle
      esotropia (> 30 to 40 prism diopters [delta]), amblyopia, inferior oblique
      overaction, dissociated vertical deviation, latent nystagmus, and cross-fixation.
      The success of antiaccommodative therapy, if attempted, was also evaluated.
      RESULTS: Of 100 patients with infantile esotropia, 15 (15%) were found to have at
      least +2.25 D. This represented 8% of all patients with accommodative esotropia
      seen over the same time period. The average age at initial examination was 21
      months, although the reported age of onset in all cases was 6 months or less. Two
      had surgery before presenting to our institute. Eleven of 13 (84%) had 40 delta
      or less. Six (40%) of the 15 had amblyopia, 5 (33%) had inferior oblique
      overaction, 3 (20%) had dissociated vertical deviation, 1 (7%) had latent
      nystagmus, and 4 (27%) had cross-fixation. Of the 13, 7 were given glasses
      initially, with 3 being fully corrected. Six were not given glasses, all had
      surgery, and all were given glasses postoperatively for a residual esotropia.
      CONCLUSION: Fifteen percent of infantile esotropia patients and 8% of
      accommodative esotropia patients have infantile accommodative esotropia. Other
      characteristics of infantile esotropia may be present, but are less frequent, and
      at least 40% are fully corrected with spectacles indicating that when the
      hyperopia is 2.25 D or greater, antiaccommodative therapy should be instituted
      before surgery.

PMID- 10204134
TI  - Managing bilateral or unilateral corneal opacities.

PMID- 10204135
TI  - Non-Hodgkin's lymphoma in a child with congenital aniridia.

PMID- 10204136
TI  - Metastatic rhabdomyosarcoma presenting as an isolated lateral rectus restriction.

PMID- 10204137
TI  - Avulsion of the optic disc after a blow to swimming goggles.

PMID- 10204138
TI  - Treatment of strabismus fixus convergens.

PMID- 10204139
TI  - Adduction deficiency following a large medial rectus recession in Duane's
      retraction syndrome type 1.

PMID- 10204140
TI  - The use of CT scanning in the diagnosis of protuberant congenital corneal
      opacities.

PMID- 10204141
TI  - [The effect of systemic changes on sick-day absenteeism in the workplace. II.
      Causes of work disability among persons under termination of employment].
AB  - During the period of transformations and restructuring of workplaces in Poland,
      the reduction of employment becomes quite common, what seems to make a
      considerable impact on sick absenteeism. The analysis presented aimed at defining
      how far the risk of sick absenteeism increases among workers under termination of
      employment because of different reasons, and indicating morbidity causes in case
      of which sick absenteeism is most extensive. The study was carried out in one of
      the largest plants of the motor car industry (before the process of
      restructuring), and it covered a cohort of 5,373 men and 3,215 women employed
      during the years 1989-94. The workers who terminated their employment during
      those years made 77% of the whole cohort under study. The case index, calculated
      as the ratio of the number of cases to the number of man-days under observation,
      was taken as an analysis parameter. Poisson regression model involving a number
      of variables (age, departments, current workers, workers discharged according to
      particular reasons, and the period preceding the termination of employment) was
      used in the statistical analysis. The study indicated an increased risk of sick
      absenteeism in the group of workers approaching the termination of employment in
      comparison with that among current workers. The highest risk of work disability,
      both among men and women, was observed in persons leaving their jobs because of
      long-lasting illness or disability pension. The highest risk indices were noted
      in men whose sick absenteeism was caused by neoplasms (RR = 14.42); endocrine
      secretion disorders (RR = 4.83); cardiovascular disorders (RR = 3.60); mental
      disorders (RR = 3.04); and diseases of the musculoskeletal system (RR = 2.95);
      and in women with neoplasms (R = 6.42); diseases of the musculoskeletal system
      (RR = 4.01); and cardiovascular diseases (RR = 3.99). Risk of sick absenteeism
      was over 50% higher among retiring workers than among current workers (RR = 1.50
      for men; and RR = 1.53 for women). Among workers discharged because of economic
      reasons, statistically significant risk of sick absenteeism was also observed (RR
      = 1.51 for men; and RR = 1.37 for women). In the group of workers leaving their
      jobs, following the agreement of the parties, an increased risk of sick
      absenteeism was noted in men (RR = 1.45). The economy transformation processes
      make a considerable impact on the occurrence of sick absenteeism in workplaces.
      Workers leaving their jobs because of health problems or of their own accord, as
      well as those discharged because of economic reasons belong to the highest risk
      groups.

PMID- 10204142
TI  - [Vibration syndrome and occupational exposure in Poland].
AB  - The objective of the study was to analyse the data on the exposure to vibration,
      and the incidence of vibration syndrome in individual branches of the national
      economy and voivodships. The data were obtained from the records of The Nofer
      Institute of Occupational Medicine in Lodz, containing reports submitted to the
      Institute every three years, and the literature on fragmentary analyses of this
      kind of exposure. Although, the number of persons exposed to vibration, and the
      incidence of occupational diseases induced by vibration have decreased, the
      material collected provide evidence that vibration syndrome still plays an
      essential role in occupational pathology. The decrease in the vibration syndrome
      incidence observed during the years 1982-97 was lower than the decline in the
      number of persons exposed to vibration, but the ratio of the number of cases to
      the number of those exposed remained unchanged (2.1). In 1994-97, forestry
      workers constituted the largest working population exposed to vibration, and the
      number of persons with diagnosed vibration syndrome significantly increased,
      however, exposure to vibration in this branch of economy considerably declined.
      In the mining industry, a significant decrease in the number of persons exposed
      to vibration, as well as in the incidence of vibration syndrome was observed at
      that time. The worse situation in forestry might result from the past negligence
      of hygiene norms or less effective diagnosis in early stages of the disease
      development. The lack of measuring and monitoring of vibration intensity in the
      working environment is an alarming observation in view of the fact that both the
      number of persons exposed, and the incidence of occupational diseases caused by
      this kind of exposure are still high.

PMID- 10204143
TI  - [The effect of occupational exposure to noise among tractor drivers: assessment
      based on 'noise threshold'].
AB  - The effects of occupational exposure to noise was analysed among operators of
      agricultural tractors (n = 172). The assessment was based on a parameter called
      'noise immission level' (dose connected with the period of employment). The study
      showed that the correlation between hearing loss and noise immission dose was
      stronger than that between hearing loss and the period of employment. Equations
      of simple regression presented in this paper allow us to make a prognosis
      concerning the risk of occupational deafness and to develop the system of the
      prevention interventions. The results obtained indicated that the parameter of
      hygiene evaluation of exposure to noise, called 'noise immission level' should be
      used more frequently for the noise measurement, especially in the prevention of
      occupational diseases.

PMID- 10204144
TI  - [Evaluation of occupational exposure to infrasonic noise].
AB  - This papers presents the results of infrasonic noise measurements performed at
      various workplaces in industry and transportation in Poland. The study concerned
      noise emitted by 124 different types of machinery, appliances and means of
      transport. The measurements were made under typical conditions of work and with
      reference to Polish norm PN-86/N-01338 and international norms ISO 7196:1995 and
      ISO 9612:1997. According to PN-86/N-01338, within octave bands of 8 divided by
      31.5 Hz, the acoustic pressure exceeding the admissible levels for (a) workers'
      health protection were found in 5 (4.0%) cases; (b) proper conditions for
      performing basic functions in observational dispatcher cabins, etc.--in 77
      (62.1%) cases; and (c) premises for administration, design offices, etc.--in 92
      (74.2%) cases. The hearing threshold was exceeded in 66.9 of all the machinery
      under study.

PMID- 10204145
TI  - [Assessment of acute neurotoxic effect of exposure to certain organic solvents
      based on an analysis of bioelectric function of the rat cerebral cortex].
AB  - The aim of this study was to assess the effect of four organic solvents (toluene,
      mesitylene, pseudocumene and hemimellitine) on the central nervous system (NCS)
      on the basis of changes in spontaneous EEG of the cerebral cortex and hippocampus
      functions occurring under conditions of acute exposure. Electrophysiological
      experiments were performed on rats with electrodes chronically implanted in the
      selected brain structures. The peripheral blood solvent concentrations were
      determined in rats operated without using gas chromatography combined with head
      space technique. Electrophysiological examinations revealed statistically
      significant quantitative changes in the cerebral cortex and hippocampus
      electroencephalograms after i.p. injections of equimolar solvents. The
      relationship between changes in spontaneous EEG and solvent concentrations in the
      blood was indicated. It was found that the central nervous system is mostly
      affected by the solvent whose concentration in blood is lowest (hemimellitine).

PMID- 10204146
TI  - [Acute poisoning by carbon monoxide affecting the extrapyramidal system].
AB  - A case record of a 19-year old women acutely poisoned by carbon monoxide is
      presented. The state of the patient was very serious with loss of consciousness,
      cerebral oedema and acute circulatory failure, manifested by pulmonary oedema.
      The presence of carboxyhemoglobin in concentration of 45% was found in the blood.
      During the second week after the incident, extrapyramidal symptoms, manifested by
      hyperkinetic-hypokinetic syndrome with predominant involuntary movement, was
      observed. The diagnostic examinations of the central nervous system showed
      necrosis of globus pallidus, external capsule and a part of internal capsule.

PMID- 10204147
TI  - [Application of BMD models in quantitative evaluation of carcinogenic risk].
AB  - The characteristics of the relationship between the exposure level and the
      incidence of harmful health effects is a general objective of assessing health
      risk related to chemical exposure. A real dose-response relationship,
      particularly for low doses, is usually unknown thus it can only be deduced on the
      basis of biological and statistical considerations. Low dose risk estimation
      requires extrapolation beyond the range of data observed. Nowadays, quantitative
      risk assessment encounters certain duality as linear models are mostly used in
      evaluation of environmental exposure, and nonlinear models are most frequently
      applied in occupational exposure. Bearing in mind that the assumption on the dose
      response linear relationship is an apparent simplification built on our lack of
      knowledge of carcinogenic mechanisms, it seems that the proposal of the US
      Environmental Protection Agency (US EPA) to use benchmark dose methods (BMD) for
      exposure effects manifested by neoplasms, is the compromise between a
      conservative approach of the EPA towards risk modelling resulting from the
      limited knowledge of these mechanisms and lack of criteria for selection of
      nonlinear models. In the case of carcinogenic risk assessment, this solution
      involves the identification of so called 'cut off point' by applying relevant
      statistical models. The cut off point indicates the exposure level that
      contributes to the increase in risk by 10%, 5% or 1%. Another possibility is to
      use interspecies extrapolation methods for the cut of point modification, and
      then draw a line between the cut off point and the beginning of the system of co
      ordinates. Since it is not feasible to apply a complete BMD methods for certain
      chemicals (e.g. bezo(a)pirene), not because of chemical properties, but due to
      insufficient experimental experience, it is proposed to use the method of
      sticking together a straight line and a curve in relation to a two-grade curve
      and not to its confidence limitation.

PMID- 10204148
TI  - [Ergonomic aspects in the prevention of occupational cumulative trauma disorders
      of the locomotor system].
AB  - In recent years, a rapid increase in the number of cumulative trauma disorders
      (CTDs) induced by repeatability of certain functions in the course of work
      performance has been observed. In the United States, a twenty-fold increase in
      the number of registered CTDs of upper limbs has been noted during the last ten
      years. For example in 1993, CTDs constituted 60% of all occupational diseases. A
      similar observation was made in Australia, Canada, Japan, Sweden, the United
      Kingdom and other European countries. It is thought that this high incidence of
      cumulative trauma disorders result, to a great extent, from changes in
      technologies leading finally to almost unilateral involvement of the human
      locomotor system. Ergonomics plays a key role in the prevention of the locomotor
      system occupational traumas, since as the only one discipline, it is able to
      provide criteria for securing safety work without disturbing its inherent sense,
      namely the efficiency. Risk factors reported in Western countries will also
      emerge in Polish economy in the near future. In Poland like in other countries,
      employers, managers of work posts, safety and hygiene services, as well as
      occupational physicians frequently fail to identify CTD risk factors which occur
      in the working environment. In this paper, the author presents the literature
      data on CTD etiology, and the criteria for identifying occupational risk factors.
      The literature review clearly indicates that the studies of cumulative trauma
      disorders of the musculoskeletal system has recently been intensified. But the
      evaluation criteria, nomenclature and analytical methods still needs to be
      standardized.

PMID- 10204149
TI  - [The effect of heavy metals (lead, cadmium, and manganese) on the function of the
      visual system].
AB  - The effect of the eyesight intoxication by heavy metals (lead, cadmium and
      manganese) is presented. The most common and dangerous forms of the eye
      intoxication are caused by lead additionally reinforced by cadmium. In various
      cases some changes in the eye may be also induced by manganese. Young organisms,
      as well as human embryos and fetuses are particularly vulnerable to the effect of
      heavy metals. Adults in general, and workers in particular, seem to develop their
      own system of adaptation. Nevertheless, despite the absence of clinical symptoms
      they should also be given regular check-ups.

PMID- 10204151
TI  - Consensus statement on prevention and early diagnosis of lung cancer. Varese,
      Italy, December, 1998.

PMID- 10204150
TI  - [The role of formaldehyde in the occurrence of contact allergy].
AB  - The authors present the major sources of formaldehyde, and discuss the incidence
      of contact allergy to this compound in Poland and throughout the world. The
      attention was turned to an increasing trend in the incidence of allergy in
      question, as well as to the problem of cross-sensitization to other chemical
      compounds of the aldehyde group (glyoxal, glutaraldehyde, succinaldehyde and
      cinnamic aldehyde).

PMID- 10204152
TI  - Innovative breast cancer education programs for African-Americans.

PMID- 10204153
TI  - Therapy for early-stage colorectal cancer.
AB  - Surgery is the only curative option for patients with colorectal cancer. The goal
      of other modalities, such as chemotherapy, immunotherapy, and radiotherapy, is to
      prolong survival and reduce the risk of recurrence. Adjuvant treatment is
      mandatory for patients with stage III colon cancer. At present, 6 months of
      fluorouracil (5-FU) plus leucovorin (folinic acid) can be considered standard
      therapy. The data on stage II colon cancer are less convincing, and perhaps only
      subgroups benefit from adjuvant therapy. Patients with stage II disease should be
      encouraged to participate in randomized trials. Outside of such trials, one can
      consider prognostic factors in the decision to offer adjuvant therapy. Patients
      with T3 or N1-3 M0 rectal cancer should receive combined-modality therapy, i.e.,
      5-FU-based chemotherapy and irradiation. Until ongoing trials answer the question
      of whether a patient should be irradiated preoperatively or postoperatively, the
      type of surgery determines the timing of irradiation. If the tumor is amenable to
      a sphincter-preserving operation, surgery can be followed by radiation therapy.
      In patients with fixed tumors and those in whom resectability is an issue,
      prolonged preoperative radiotherapy is more appropriate. Ongoing trials should
      optimize existing adjuvant therapy (by achieving an ideal balance between
      toxicity and effectiveness) and integrate the advantages of recently approved
      drugs.

PMID- 10204154
TI  - Prostate cancer risk assessment program. A model for the early detection of
      prostate cancer.
AB  - Prostate cancer is the most common form of cancer (except skin cancer) in men.
      Several factors have been associated with an increased risk for prostate cancer,
      including age, ethnicity, family history, lifestyle, and environmental exposures.
      Recognition of the importance of the interaction of these factors in prostate
      cancer has led to an interest in their evaluation as a model both for studying
      genetic susceptibility patterns and for studying and providing educational tools
      and preventive interventions. One such model has been developed at Fox Chase
      Cancer Center. Critical to the implementation of the model has been the
      establishment of the Prostate Cancer Risk Registry (PCRR) and Prostate Cancer
      Risk Assessment Program (PRAP). Together, they serve as a unique resource for
      investigating the interaction between environmental factors and genetic
      susceptibility patterns; exploring the early, premalignant biological markers of
      prostate cancer; and prospectively assessing the quality of life (QOL) of men at
      risk. In addition, PRAP facilitates the evaluation of models for prostate cancer
      risk counseling and screening in the community. This paper describes this model
      for early detection and risk reduction, along with preliminary data from its
      first two study aims. The program is particularly relevant in view of the wealth
      of genetic information emerging from the Human Genome Project.

PMID- 10204155
TI  - Use of brachytherapy to preserve function in children with soft-tissue sarcomas.
AB  - Pediatric soft-tissue sarcomas are managed with a multimodality treatment program
      that includes surgery, chemotherapy, and external-beam radiotherapy
      (teletherapy). The use of teletherapy in young children can result in significant
      long-term toxicities (especially growth retardation of bones and organs).
      Brachytherapy, if feasible, is an attractive alternative for the treatment of
      pediatric soft-tissue sarcomas, since it irradiates small volumes and, thus, may
      potentially minimize complications. Aggressive chemotherapy is used to achieve
      systemic control and tumor shrinkage, thereby facilitating conservative surgery
      and brachytherapy. The brachytherapy techniques used in children are similar to
      those employed in adults. Low-dose-rate (LDR) brachytherapy with manually
      afterloaded removable iridium-192 is commonly used, although it is associated
      with some radiation exposure hazards. Low-energy radionuclides (e.g., iodine-125)
      and remote afterloading technology have been used to reduce radiation exposure
      hazards. Brachytherapy, in conjunction with chemotherapy and surgery but without
      supplementary teletherapy, has produced good local control with acceptable late
      complications in selected patients with localized tumors. Brachytherapy can also
      be used as a boost to moderate dose external-beam radiotherapy for more extensive
      tumors. The use of newer modalities, such as high-dose-rate, pulsed-dose-rate,
      and intraoperative brachytherapy, has allowed brachytherapy to be given to
      younger children and infants, but the long-term morbidities of these modalities
      need to be established.

PMID- 10204156
TI  - Clinical trials referral resource. Multicenter trials of therapies for adult
      brain tumors.

PMID- 10204157
TI  - AIDS drugs effective against most common HIV strain.

PMID- 10204158
TI  - Treatment of estrogen deficiency symptoms in women surviving breast cancer. Part
      3: Prevention of osteoporosis and CV effects of estrogens and antiestrogens.

PMID- 10204159
TI  - Master switch may help cancer cells hide from the immune system.

PMID- 10204160
TI  - [The role of the posterior hypothalamus in the regulation of paradoxical sleep].
AB  - Posterior hypothalamus was found to take part in the inhibitory control of the
      paradoxical sleep executive mechanisms responsible for the ECoG desynchronisation
      and phasic events. Functional activity of the posterior hypothalamus seems to be
      at its lowest during the paradoxical sleep stage as characterised by phasic
      events and the ECoG desynchronisation, and increases during the stage with alpha
      like activity in the ECoG and absence of phasic events, the latter having,
      probably, a "sentinel" function.

PMID- 10204161
TI  - [Comparison of atrial premature depolarization topography during vagal
      stimulation and humoral acetylcholine administration].
AB  - Epicardial atrial mapping in open-chest dogs during different cholinergic
      influences has shown that, in acetylcholine administration and vagal stimulation,
      spatial distribution of atrial premature depolarisation (APDs) seems to be
      similar to prevalence of ectopic sources from both atria and atrial septum.
      Spatial distribution of the APDs in acetylcholine administration in the sinus
      node artery was limited to the region of this artery so that the APDs mainly
      arise from intercaval area of the right atrium and from atrial septum, but never
      from the left atrium. The latent pacemakers spread over both atria and atrial
      septum, could participate in initiation of cholinergically-induced APDs and
      atrial fibrillation. A direct effect of acetylcholine seems to be necessary for
      development of arrhythmic activity of the latent pacemakers.

PMID- 10204162
TI  - [The role of endothelial mechanosensitivity in vessel bed responses to changes in
      blood pressure in cats].
AB  - In 19 anaesthetised cats, the response of vascular bed to increasing perfusion
      pressure at a constant blood flow perfusion consisted of two phases: a myogenic
      constriction and a subsequent arterial dilatation. The latter depended on ability
      of the endothelium to relax the smooth muscle under stress. The findings suggest
      that the control of the smooth muscle tone by a stress has to fight against the
      myogenic constriction and thus determines the changes in vascular resistance
      induced by an increased arterial pressure.

PMID- 10204163
TI  - [Implantation of an ultrasonic indicator into the pudendal artery to study the
      blood flow volume in the cow mammary gland].
AB  - The cow mammary gland blood flow was found to equal 601.8 litres per a litre of
      milk at a daily yield 5 litres, whereas at a decreased daily yield (3.7 l/day)
      the blood flow was equal 452 litres per every litre of milk.

PMID- 10204164
TI  - [Noradrenaline synthesis during the first week of life and development of
      inherited stress-induced arterial hypertension in rats].
AB  - Increasing of the noradrenaline synthesis with daily i.p. administration of
      synthetic noradrenaline precursor DL-Threo on the 21-25th day of life of the rats
      with inherited stress-induced arterial hypertension (ISIAH) resulted in a drop of
      basal and stress-induced blood pressure in adult animals with no changes in
      response of the hypothalamic-pituitary-adrenocortical system (HPAS). Reduction of
      the noradrenaline synthesis with daily i.p. administration of dopamine
      hydroxylase inhibitor FLA-57 in 21-25th day old Wistar rats induced no arterial
      hypertension in adults but decreased their adrenocortical response to emotional
      stress. Noradrenaline deficit in the brain structures on the 4th week of life in
      rats seems to be associated with arterial hypertension only in presence of
      genetic defect determining this pathology. Changes in adult HPAS function due to
      shortage of noradrenaline in the brain in the end of the 1st month of life do not
      depend on hypertension.

PMID- 10204165
TI  - [The role of HSP70 and Ca(2+)-pump from the myocardial sarcoplasmic reticulum in
      cardioprotective effects during adaptation to physical load in rats].
AB  - In the course of adaptation to exercise, enhanced resistance of isolated heart
      against ischemia and reperfusion correlated with accumulation of cytoprotective
      proteins of the HSP70 family and increased potency of sarcoplasmic reticulum (SR)
      Ca2+ pump in the rat myocardium. Blockade of the HSP70 synthesis with guercetin
      prevented development of protection of the heart against ischemia and
      reperfusion. In the course of the adaptation, the increased resistance of the
      Ca2+ pump against detrimental factors preceded its potentiation. The findings
      suggest that the HSP70 accumulation and increased potency and resistance of the
      SR Ca2+ transport system in the myocardium are important mechanisms of adaptive
      protection of the heart.

PMID- 10204166
TI  - [mu-Opiate receptor activation and increase in heart resistance to ischemic and
      reperfusion injury].
AB  - Stimulation of mu-opioid receptors was found to contribute to prevention of
      myocardial contractile dysfunction and ventricular arrhythmias in ischemia and
      reperfusion of the rat isolated heart. Endogenous agonists of the mu-opioid
      receptors were not involved in tonic regulation of the heart resistance against
      reperfusion disturbances of the rhythm and contractility. On the other hand, mu
      opioid receptors are important for development of postischemic contracture.

PMID- 10204167
TI  - [Dependence of arterial pressure and cardiac output on initial (regulated)
      arterial tone during beta-adrenoreceptor stimulation in rats].
AB  - A significant decrease of arterial pressure in response to isoproterenol occurred
      in anaesthetised rats with the initial pressure 101-130 mm Hg. Elevation of the
      initial pressure up to 131-180 mm Hg led to a significant attenuation of the
      depressor effect. The correlation analysis revealed transformation of direct
      correlation into inverse one between the depressor responses to isoproterenol and
      the degree of elevation of the initial arterial tone, as well as lack of such a
      dependence in the cardiac output shifts.

PMID- 10204169
TI  - [Effect of albumin on the Na, K-ATPase activity in the rat erythrocytes during
      immobilization stress].
AB  - Immobilisation stress (IMS) led to a 42% decrease in erythrocyte Na, K-ATPase
      activity in rats. Pre-treatment of the "stressed" erythrocytes with human serum
      albumin (HSA) and 1-day exposition of the HSA prior to the IMS led to stabilising
      of enzyme activity at the control level. Absence of inhibiting effect of non
      protein supernatants of the blood plasma of stressed rats on enzyme activity of
      normal erythrocytes was shown in presence of the HSA both in vitro and in vivo.
      The mechanism of the HSA protective effect on the Na,K-ATPase activity of
      erythrocytes in the IMS, is discussed.

PMID- 10204168
TI  - [Metabolism of the androgenic precursor androstenedione and effects of aromatase
      inhibitors in cultured blood lymphocytes].
AB  - Blood lymphocytes from 26 women were cultivated in RPMI-1640 for 72 hrs with or
      without dexamethasone, dbcAMP, and TPA. Androstenedione conversion was most often
      activated by the dbcAMP, then by Dex and TPA. Response to dbcAMP was most obvious
      in women under 50, whereas response to Dex--in women over 50. Aromatase inhibitor
      fadrosol displayed a tendency towards prevention of the activation of
      androstenedione conversion in cultivated lymphocytes. A possibility of aromatase
      gene induction in cultivated lymphocytes cannot be completely excluded and
      demands further investigation with the aid of molecular-genetic methods.

PMID- 10204170
TI  - [Interaction of the angular and linear components of the horizontal vestibulo
      ocular reflex in the pigeon].
AB  - Pigeons were exposed to centric and eccentric horizontal rotations in darkness by
      velocity trapezoid. Different in sign the duration alterations of the opposite
      directed horizontal eye nystagmus occurred during otolith membrane shifts in
      sagittal as well as frontal planes. A direct dependence was found between the
      duration alterations of the primary nystagmus phase and the peak value
      alterations of its slow phase velocity under increased (but not decreased)
      centrifugal force. In the both cases, if duration of the primary nystagmus phase
      was enlarged, duration of its secondary phase was diminished and vice versa. It
      suggests the otolith component does not decay up to zero by constant velocity and
      at once after rotation; by deceleration it is biphasic. In affirms the own
      hypothesis that the linear component is asymmetric central neuronal activity that
      modifies the canal component even if this activity by itself is not enough for
      eye movement initiation.

PMID- 10204171
TI  - [Effect of nitrite on the excitability of brain neurons in helix].
AB  - Incubation of the Helix brain in sodium nitrite (SN) decreased the firing
      threshold of silent neurones, increased firing rate and a response to
      stimulation, activated excitatory synaptic inputs of the neurones under study.
      The effects were stable but reversible. Rapid responses to the SN application
      were only shown for spontaneously active neurones. The SN effects were
      accompanied by a depolarisation and an increase in the input resistance.
      Inhibitor of the NO synthase exerted opposite effects to the NO donors and SN. A
      possible role of the NO and hypoxia in the SN effects, is discussed.

PMID- 10204172
TI  - [Interdigestive stomach motor activity in dogs during stimulation of the duodenal
      receptors by sodium oleate].
AB  - Administration of 20% sodium oleate solution in the duodenum of awake dogs
      suppresses stomach contractions and decreases duration of the postprandial motor
      complex. Benzohexonium eliminates these oleate effects. The findings suggest that
      the oleate activates cholinergic vago-vagal reflex which modifies the
      postprandial motor complex.

PMID- 10204173
TI  - [Neuroanatomical and functional organization of the pre-Botzinger complex in the
      cat].
AB  - The technique of horseradish peroxidase retrograde axonal transport and local
      electrical stimulation of the pre-Botzinger complex was used to study the
      connections between neurones of the bulbar respiratory nucleus and descending
      pathways from bulbar nuclei in the cat spinal cord. A possible role of the nuclei
      under study for rhythmogenesis of breathing and respiratory control, is
      discussed.

PMID- 10204174
TI  - [The role of prostaglandin E2 and its receptors in the regulation of osmotic
      permeability of the frog bladder epithelium].
AB  - Arginine-vasotocin-induced enhancement of osmotic water flow was inhibited by
      PGE2, sulprostone, M&B 28767 and 17-phenyl-omega-trinor PGE2. The inhibitory
      action of these agents except M&B 28767 was more obvious when the osmotic water
      flow was activated by dibutyryl-cAMP. The findings suggest that, in the frog
      urinary bladder, the inhibitory effect of the PGE2 on arginine-vasotocin-induced
      water flow appears to be mediated via two receptor subtypes coupled with
      different secondary messengers. The inhibition-sensitive targets are localised
      both on pre- and post-cAMP steps of the hormonal signal transduction pathway.

PMID- 10204175
TI  - [Effects of the microwave radiation from the cellular phones on humans and
      animals].
AB  - Biological effects of the mobile phone microwave radiation were shown to depend
      on many factors: the duration of the irradiation, individual characteristics of
      the CNS and immune systems, and others. The cellular phone microwave radiation
      can induce reversible unspecific adaptive responses if it is short and the
      organism is very radiosensitive. A long-term exposure (over one year) combined
      with the organism weakened immune system may produce a cumulative effect in the
      form of stress responses, various damages and, in some cases, even cancer. The
      ultimate result of the microwave exposure depends on the balance between induced
      damage and the organism reparative ability.

PMID- 10204176
TI  - [Complex system for respiration studies in animals].

PMID- 10204177
TI  - [Co-housing in the group with stable hierarchy is not aversive for dominant and
      subordinate animals].
AB  - Behaviour of individuals and their responses to external stimuli are controlled
      by the micro-social environment in which most mammals are subject to dominant
      subordinate relations. Physiological (pain sensitivity, immunological data:
      thymus and spleen weight, first immunological response) and behavioural
      (locomotor activity, shuttle-box behaviour) signs were studied in dominant and
      subordinate male mice of linear hierarchy groups. No significant difference was
      found between both groups of sings in both groups of the animals. Housing of
      dominant with subordinate mice seems not to be aversive for both types of the
      animals.

PMID- 10204178
TI  - [Immunohistochemical study of structural basis of inhibition in central
      cerebellar nuclei].
AB  - Glutamatic acid decarboxylase (GAD): a synthetic enzyme for inhibitory
      neurotransmitter GABA, was studied in the central cerebellar nuclei. Synapses
      were found: morphological structures providing of inhibition in the central
      cerebellar nuclei.

PMID- 10204179
TI  - [Effects of stimulation and damage of afferent nerves on the glucose and free
      fatty acid levels in the rat blood under various glycemic conditions].
AB  - Capsaicin stimulation of afferent neurones increased hyperglycaemic responses to
      glucose and decreased hypoglycaemia in control rats. Elevation of the free fatty
      acids level occurred following both the stimulation alone and that combined with
      insulin. Neonatal capsaicin pre-treatment decreased the hypoglycaemic response
      effect of insulin and the FFA level. Treatment of adult rats with capsaicin did
      not affect hypoglycaemia following insulin administration but did decrease the
      FFA level. In capsaicin pre-treated rats, the capsaicin stimulation exerted no
      effect upon the hypoglycaemia following insulin administration but abolished the
      insulin effect on the FFA level. The findings suggest that the capsaicin
      sensitive nerves play a major role in mediating the glucose and the FFA metabolic
      responses.

PMID- 10204180
TI  - [Left and right brain hemispheres in the regulation of pain sensitivity
      biorhythms in mice during stress].
AB  - The foot-shock effects on ultradian and circadian rhythms of pain sensitivity in
      the SHR mice were studied after unilateral brain cortex hemisphere inactivation
      by means of the Leao spreading depression. Under acute painful stress, the left
      hemisphere partially loses its synchronizing effect on circadian rhythm and
      supports the 12-hour and particularly 6-hour periodicities. The left hemisphere
      effect dominates in intact animals under stress. The right hemisphere under the
      same conditions mainly loses its activating effect on circadian rhythm and
      supports the 8- and 16-hour periodicities. The right hemisphere effect dominates
      in animals under stress operated 2-3 days prior to the experiment.

PMID- 10204181
TI  - [Fragmental regulation of vestibuloocular responses].
AB  - Intact pigeons were exposes to whole body centric and eccentric horizontal
      rotations in darkness during angular velocity trapezoids. The overall nystagmus
      alteration patterns were analysed. In 10 pigeons, all nystagmus alterations may
      be explained on the basis of the dynamics of peripheral otolith activity and
      central effects that are the same for all combinations of interacting inputs
      (type 1 patterns), whereas in other pigeons part of the nystagmus alterations
      were connected with some central effects that were individually specific and
      touch upon the responses to separate combinations of interacting input (type 2
      patterns). It was observed the transformation of type 2 to type 1-patterns during
      the reiterated rotational trails and light nembutal anesthesia. A fragmentary
      control of the vestibulo-ocular responses seems to exist. This implies that the
      CNS is able to discern numerous kinds of bilaterally organized interacting inputs
      arising during different otolith membrane shifts.

PMID- 10204182
TI  - [Improvement of the selective perception and learning with the analog of C
      terminal fragment of vasopressin in rats].
AB  - New analogue of the AVP(6-9), the D-MPRG was administered intranasally in
      different doses. The administration improved the process of conditioning. The
      most efficient dose turned out to be 0/01 mcg/kg. Tetrapeptide administered 1
      hour before each learning session and immediately after it accelerated the
      avoidance conditioning. The peptide effect was more obvious in conditioning with
      a negative reinforcement. The data obtained suggest that the D-MPRG mostly
      affects the perception of experimental environment as well as improves the
      consolidation of memory traces. The peptide was also shown to delay extinction of
      previously learned skills.

PMID- 10204183
TI  - [Involvement of amygdala central nucleus in the regulation of cardiovascular
      functions].
AB  - Effects of high frequency stimulation of the amygdala central nucleus involved a
      selective decrease in the activity: an increase in the activity of the inferior
      cardiac nerve and a simultaneous decrease in the activity of the vertebral nerve,
      as well as an obvious BP increase. Bilateral electrolytic lesions of the same
      amygdala structure accompanied with an overload of the higher nervous activity
      induced no hypertensions. The role of the amygdala central nucleus in control of
      cardiovascular functions is discussed.

PMID- 10204184
TI  - [Spectral EEG characteristics in emotional stress model in cats].
AB  - Emotional stress induced a global activation of the brain electrical activity: a
      decrease in the power of the theta-, alpha-, and beta-1-frequency bands in
      animals with active behaviour, and a decrease in the power of the theta- and
      alpha-frequency bands in animals with behavioural inhibition. The findings
      suggest that two forms of emotional behaviour correspond to different patterns of
      the brain activity. Appearance of spindle-like activity in passive animals'
      parietal and occipital leads suggests a hypothetical suppression in associative
      parietal and visual neocortical areas involved in processing the sensory
      information.

PMID- 10204185
TI  - [Responses of hypophyseal-adrenocortical system to stressor during repeated
      stress].
AB  - The corticosterone concentrations were determined in the blood of unrestrained
      rats exposed to 7 successive trials with 30-min. intervals. This study revealed
      that hormonal responses of the pituitary-adrenocortical system to stress were
      decreased, whereas the time of the system recovery was reduced after re-exposure
      to electric shock. The change seems to be dependent on the strength of the stress
      agent and the number of re-exposures.

PMID- 10204186
TI  - [Delta-opiate receptors and heart resistance to arrhythmogenic factors].
AB  - Stimulation of peripheral delta-opioid receptors exerted no effect on
      arrhythmias, whereas that central delta 1- and delta 2-receptor activation
      decrease the heart susceptibility to arrhythmogenic action of epinephrine. Pre
      treatment with the delta-opioid receptor antagonist ICI 174 prevented the
      antiarrhythmic effect of the central delta-receptors stimulation. The findings
      suggest that the heart decreased vulnerability to epinephrine-induced arrhythmias
      following the central delta-receptors stimulation is mediated by an enhanced
      vagal activity.

PMID- 10204187
TI  - [The role of intra- and extracellular calcium sources in the rhythmic inotropic
      regulation of isometric contractions in the chick embryo myocardium].
AB  - Isometric contractions and force-frequency relationships (FFR) were assessed in
      isolated ventricular preparations of 3- and 4-day chick embryos (EM) and
      posthatched (PH) chicks. Pacing protocols for the FFR assessment were applied in
      normal buffer, buffer with 50% and 25% of normal Na+ concentration, and in buffer
      with ryanodine. PH myocardium showed greater peak force and more prominent FFR
      than EM. 50% low Na+ superfusion induced positive inotropic effect and increase
      in the FFR in PH and EM. 25% low Na+ superfusion induced negative inotropic
      effect and suppressed FFR more prominent in EM. Ryanodine more suppressed FFR in
      PH myocardium. The observed age-dependent differences substantiate the fact that
      Na-Ca exchange plays a leading role in the FFR regulation in early embryonic
      myocardium and sarcoplasmic reticulum plays a leading role in PH myocardium.

PMID- 10204188
TI  - [Effects of various concentrations of erythropoietin on cultured erythroblast
      islands].
AB  - Proliferative effects of increasing concentrations of erythropoietin were studied
      in vitro. The maximal amount of erythroblastic islands consisting of residual
      macrophages and erythroid cells was observed with the doses 0.5 to 1.5 ME/ml of
      erythropoietin. Smaller doses stimulated the reconstruction of erythroblastic
      islands.

PMID- 10204189
TI  - [Selective inhibition of inducible NO-synthase by nonselective inhibitor].
AB  - The study has shown that Nw-nitro-L-arginine, a nonselective nitric oxide (NO)
      inhibitor, in low non-vasoactive doses (10 mg/kg) exerted a protective effect in
      heat shock as demonstrated by a decrease in the mortality rate and prevention of
      acute hypotension in rats. The L-NNA in the same dose inhibited the basal NO
      production but left unaffected a carbachol-activated NO production. The findings
      suggest a possibility in principle of preferential inhibition of inducible NO
      synthase in pathological conditions related to the NO overproduction using non
      vasoactive doses of L-NNA the nonselective NO-synthase inhibitor.

PMID- 10204190
TI  - [Experimental model of subfebrile condition of central origin].
AB  - Central model of subfebrility was experimentally developed using administration
      of fresh homologous blood from an unanesthetised donor into the rat brain lateral
      ventricle. Rectal temperature significantly increased by the end of the 1st day
      of the administration. Duration of the hyperthermic response was about 8 days.
      The body temperature rise varied from 0.45 to 0.7 degrees C. The central
      subfebrility had no initial fenrile phase. An increased level of glucose in the
      blood serum during central subfebrility suggests an altered activity of the
      sympathetic nervous system to be one of the causes of the subfebrility
      development.

PMID- 10204191
TI  - [Urokinase induces adhesion of monocytes to fibrinogen].
AB  - Urokinase activates adhesion of monocytic U937 cells to fibrinogen-coated
      surface. This effect is due to urokinase proteolytic activity and does not depend
      on the urokinase binding to its receptor.

PMID- 10204192
TI  - [Long-lasting reduction of the threshold of epileptiform discharges induced by
      periodic removal of extracellular Mg2+ in slices of CA1 field of the rat
      hippocampus].

PMID- 10204193
TI  - [Academician Oleg Georgievich Gazenko (on the 80th birthday)].

PMID- 10204194
TI  - Dose response studies: how do we make them conclusive?
AB  - In this paper we discuss how to make meaningful use of a dose response study. It
      is argued that concepts like the minimal effective dose are not clinically
      meaningful and that the purpose of a dose response study should be to identify
      the drug potency in relation to a known active control. We also discuss various
      ways of carrying out the analysis.

PMID- 10204195
TI  - Generalized linear mixed models for meta-analysis.
AB  - We examine two strategies for meta-analysis of a series of 2 x 2 tables with the
      odds ratio modelled as a linear combination of study level covariates and random
      effects representing between-study variation. Penalized quasi-likelihood (PQL),
      an approximate inference technique for generalized linear mixed models, and a
      linear model fitted by weighted least squares to the observed log-odds ratios are
      used to estimate regression coefficients and dispersion parameters. Simulation
      results demonstrate that both methods perform adequate approximate inference
      under many conditions, but that neither method works well in the presence of
      highly sparse data. Under certain conditions with small cell frequencies the PQL
      method provides better inference.

PMID- 10204196
TI  - Interpreting age, period and cohort effects in plasma lipids and serum insulin
      using repeated measures regression analysis: the CARDIA Study.
AB  - Observed changes in health-related behaviours and disease risk factors may arise
      from physiological or environmental changes, or from biases due to sampling or
      measurement errors. We illustrate problems in the interpretation of such changes
      with longitudinal data from the Coronary Artery Risk Development in Young Adults
      (CARDIA) study. Mean plasma cholesterol was 14 mg/dl higher in 27- than in 20
      year-old black men cross-sectionally, but longitudinally it declined by 4 mg/dl
      during the 7 years. To sort out these contradictory assessments of the effect of
      age/passage of time, we estimated age and period effects under the assumptions
      that age effects are a smooth function of age independent of period, and that
      period effects are changes common to persons across all ages. Simple estimates
      the age effect, such as the cross-sectional age slopes, may be confounded by
      cohort effects, by interactions of time and age after baseline, or by the
      occurrence of non-linearities in response after baseline. We note examples of
      each potential type of bias. The data and background literature support the
      assumption that cohort effects do not seriously compromise interpretation for
      these variables in the CARDIA study. Strong secular decreases in plasma
      cholesterol, apparently due to population-wide dietary change, mask increases
      with ageing. Age increases in triglycerides are largely explained by increases in
      body fatness. For these data, we cautiously accept the cross-sectional age slope
      as an estimate of ageing and the age-matched time trend as an estimate of secular
      trend.

PMID- 10204197
TI  - Multiple imputation of missing blood pressure covariates in survival analysis.
AB  - This paper studies a non-response problem in survival analysis where the
      occurrence of missing data in the risk factor is related to mortality. In a study
      to determine the influence of blood pressure on survival in the very old (85+
      years), blood pressure measurements are missing in about 12.5 per cent of the
      sample. The available data suggest that the process that created the missing data
      depends jointly on survival and the unknown blood pressure, thereby distorting
      the relation of interest. Multiple imputation is used to impute missing blood
      pressure and then analyse the data under a variety of non-response models. One
      special modelling problem is treated in detail; the construction of a predictive
      model for drawing imputations if the number of variables is large. Risk estimates
      for these data appear robust to even large departures from the simplest non
      response model, and are similar to those derived under deletion of the incomplete
      records.

PMID- 10204198
TI  - Estimation of failure probabilities in the presence of competing risks: new
      representations of old estimators.
AB  - A topic that has received attention in both the statistical and medical
      literature is the estimation of the probability of failure for endpoints that are
      subject to competing risks. Despite this, it is not uncommon to see the
      complement of the Kaplan-Meier estimate used in this setting and interpreted as
      the probability of failure. If one desires an estimate that can be interpreted in
      this way, however, the cumulative incidence estimate is the appropriate tool to
      use in such situations. We believe the more commonly seen representations of the
      Kaplan-Meier estimate and the cumulative incidence estimate do not lend
      themselves to easy explanation and understanding of this interpretation. We
      present, therefore, a representation of each estimate in a manner not ordinarily
      seen, each representation utilizing the concept of censored observations being
      'redistributed to the right.' We feel these allow a more intuitive understanding
      of each estimate and therefore an appreciation of why the Kaplan-Meier method is
      inappropriate for estimation purposes in the presence of competing risks, while
      the cumulative incidence estimate is appropriate.

PMID- 10204199
TI  - Iterative random aggregation of small units using regional measures of spatial
      autocorrelation for cluster localization.
AB  - A method for localization of spatial disease clusters which uses a regional
      measure of spatial autocorrelation (RSAC) was recently developed by Munasinghe
      and Morris. They found this method to be an effective tool for the identification
      of regional disease clusters. In order to reduce the spurious variability of the
      estimated relative risks, the smallest geographic units were aggregated into
      analytic areas, consisting of a predefined minimum number of persons at risk
      (PAR). We found RSAC to be a valuable method and will propose some improvements.
      The present study illustrates that RSAC is quite sensitive both to the choice of
      PAR and the aggregation algorithm. Moreover, it does not utilize all the
      geographic details provided by the data sets, for instance the disease rates of
      the geographic units within the analytic areas. In order to overcome, at least to
      some extent, these problems, a modified version of the RSAC, called IRARSAC, is
      proposed. This method uses information, provided by the RSAC, from many different
      levels of aggregation. The performance of IRARSAC was shown to be more stable as
      compared to the RSAC, and it also seems to localize a greater proportion of the
      true clustering areas.

PMID- 10204200
TI  - Combining classification trees using MLE.
AB  - We propose a probability distribution for an equivalence class of classification
      trees (that is, those that ignore the value of the cutpoints but retain tree
      structure). This distribution is parameterized by a central tree structure
      representing the true model, and a precision or concentration coefficient
      representing the variability around the central tree. We use this distribution to
      model an observed set of classification trees exhibiting variability in tree
      structure. We propose the maximum likelihood estimate of the central tree as the
      best tree to represent the set. This MLE retains the interpretability of a single
      tree model and has excellent generalizability. We implement an ascent search for
      the MLE tree structure using a data set of 13 classification trees that predict
      the presence or absence of cancer based on immune system parameters.

PMID- 10204202
TI  - Conference on meta-analysis in the design and monitoring of clinical trials.

PMID- 10204201
TI  - The study of candidate genes in drug trials: sample size considerations.
AB  - With discovery of an increasing number of candidate genes that may affect inter
      individual variability in response to drugs, the design of drug trials that
      incorporate their study has become relevant. We discuss the determination of
      sample size for such studies when the number of tests to perform is given, or,
      alternatively, the number of tests to perform when the sample size is given. In
      many cases, a uniformly most powerful test does not exist and normal
      approximations are not sufficiently accurate to determine sample size. We discuss
      briefly various tests of interest and we give simple examples to illustrate some
      of the problems that arise.

PMID- 10204203
TI  - Clinical applications of Doppler and three-dimensional ultrasound in assisted
      reproductive technology.

PMID- 10204204
TI  - Time for a more detailed prenatal examination of the umbilical cord?

PMID- 10204205
TI  - Intrauterine management of fetal parvovirus B19 infection.
AB  - OBJECTIVES: The aim of our study was to determine the outcome of pregnancies
      after intrauterine management of fetal parvovirus B19 infection. DESIGN:
      Retrospective study. SUBJECTS: A total of 37 cases of maternofetal parvovirus B19
      infection, 35 of which were associated with hydrops fetalis, were referred to our
      tertiary level center between 1989 and 1996. With regard to fetal hydrops, no
      apparent cause other than parvovirus B19 infection was found in any patient.
      METHODS: In all patients, cordocentesis was performed to assess the degree of
      fetal anemia. When anemia was present, cordocentesis was followed by intrauterine
      transfusion with packed red cells into the umbilical vein. Further management
      depended on the degree of fetal anemia and gestational age and included follow-up
      fetal blood sampling/transfusion as well as ultrasound examinations as deemed
      appropriate. RESULTS: Packed red cell transfusion was performed in 30 patients
      with significant fetal anemia (Z-score 1.6-7.8 below the mean for gestational
      age). The fetal hemoglobin values ranged from 2.1 to 9.6 g/dl. Serum levels of
      platelets in the transfusion group were 9-228 x 10(9)/l with Z-scores in the
      range of < 1 to 3.8 below the mean. During treatment and follow-up, there were
      five intrauterine deaths (13.5%), one neonatal death (2.7%) and 31 live births
      (83.8%). CONCLUSIONS: Fetal parvovirus infection can lead to marked anemia and
      hydrops formation. Cordocentesis allows precise assessment of fetal anemia which
      can then be corrected by intravenous transfusion. Under this regimen, the outcome
      proved favorable in the majority of fetuses, even those that were severely
      anemic.

PMID- 10204206
TI  - Maternal age- and gestation-specific risk for trisomy 21.
AB  - OBJECTIVE: To provide estimates of maternal age- and gestational age-related
      risks for trisomy 21. METHODS: The prevalence of trisomy 21 was examined in
      57,614 women who had fetal karyotyping at 9-16 weeks of gestation for the sole
      indication of maternal age of 35 years or more. On the basis of the maternal age
      distribution and the reported maternal age-related risk for trisomy 21 at birth,
      the expected number of trisomy 21 cases was calculated for each gestational age
      subgroup (9-10 weeks, 11-14 weeks and 15-16 weeks). The ratio of the observed to
      expected number of cases of trisomy 21 was then calculated and regression
      analysis was applied to derive a smoothened curve. The formula for maternal age-
      and gestational age-related risk was then applied to a population of 96,127
      pregnancies that were examined at 10-14 weeks to calculate the expected number of
      trisomy 21 pregnancies, and this number was compared to the observed number of
      326. RESULTS: In the 57,614 pregnancies there were 538 cases of trisomy 21. The
      relative prevalences of trisomy 21, compared to a prevalence of 1.0 at 40 weeks,
      was 10 exp(0.2718 x log(10)(gestation)2 - 1.023 x log10(gestation) + 0.9425). On
      the basis of the estimated maternal age- and gestational age-related risks, the
      expected number of trisomy 21 cases at 10-14 weeks of gestation in the 96,127
      pregnancies was 329 (95% confidence interval 291-361), which was not
      significantly different from the observed number of 326 cases (chi2 = 0.02).
      CONCLUSION: The risk for trisomy 21 increases with maternal age and decreases
      with gestation. The prevalence of trisomy 21 at 12 and 16 weeks of gestation is
      higher than the prevalence at 40 weeks by 30% and 21%, respectively.

PMID- 10204207
TI  - Characteristics of blood flow in intrauterine growth-restricted fetuses with
      hypercoiled cord.
AB  - OBJECTIVE: To clarify the characteristics of fetoplacental blood flow of growth
      restricted fetuses with hypercoiled umbilical cord. SUBJECTS: Eight growth
      restricted fetuses with hypercoiled cord. METHODS: Flow velocity waveforms of the
      umbilical cord artery and vein, fetal abdominal aorta and fetal inferior vena
      cava were analyzed. RESULTS: The resistance index in the umbilical artery in the
      hypercoiled cases was lower than that in normal fetuses. Early-diastolic reversed
      flow was observed in the abdominal aorta in some cases. In all cases, umbilical
      venous pulsation was observed in the entire cord until delivery. In one case,
      fetal heart failure occurred, resulting in pre-mature delivery. An atrophic type
      of single umbilical artery was observed in four cases. CONCLUSION: Fetal blood
      flow disturbance caused by a hypercoiled umbilical cord may be a cause of growth
      restriction.

PMID- 10204208
TI  - Prenatal diagnosis of a lean umbilical cord: a simple marker for the fetus at
      risk of being small for gestational age at birth.
AB  - OBJECTIVE: The purpose of this study was to investigate whether the prenatal
      diagnosis of a 'lean' umbilical cord in otherwise normal fetuses identifies
      fetuses at risk of being small for gestational age (SGA) at birth and of having
      distress in labor. The umbilical cord was defined as lean when its cross
      sectional area on ultrasound examination was below the 10th centile for
      gestational age. METHOD: Pregnant women undergoing routine sonographic
      examination were included in the study. Inclusion criteria were gestational age
      greater than 20 weeks, intact membranes, and singleton gestation. The sonographic
      cross-sectional area of the umbilical cord was measured in a plane adjacent to
      the insertion into the fetal abdomen. Umbilical artery Doppler waveforms were
      recorded during fetal apnea and fetal anthropometric parameters were measured.
      RESULTS: During the study period, 860 patients met the inclusion criteria, of
      whom 3.6% delivered a SGA infant. The proportion of SGA infants was higher among
      fetuses who had a lean umbilical cord on ultrasound examination than among those
      with a normal umbilical cord (11.5% vs. 2.6%, p < 0.05). Fetuses with a lean cord
      had a risk 4.4-fold higher of being SGA at birth than those with a normal
      umbilical cord. After 25 weeks of gestation, this risk was 12.4 times higher when
      the umbilical cord was lean than when it was of normal size. The proportion of
      fetuses with meconium-stained amniotic fluid at delivery was higher among fetuses
      with a lean cord than among those with a normal umbilical cord (14.6% vs. 3.1%, p
      < 0.001). The proportion of infants who had a 5-min Apgar score < 7 was higher
      among those who had a lean cord than among those with normal umbilical cord (5.2%
      vs. 1.3%, p < 0.05). Considering only patients admitted in labor with intact
      membranes and who delivered an appropriate-for-gestational-age infant, the
      proportion of fetuses who had oligohydramnios at the time of delivery was higher
      among those who had a lean cord than among those with a normal umbilical cord
      (17.6% versus 1.3%, p < 0.01). CONCLUSION: We conclude that fetuses with a lean
      umbilical cord have an increased risk of being small for gestational age at birth
      and of having signs of distress at the time of delivery.

PMID- 10204210
TI  - The development of the fetal sternum: a cross-sectional sonographic study.
AB  - OBJECTIVE: To assess the relationship between gestational age and sonographic
      appearance of the various sternal components and establish growth during human
      gestation. DESIGN: A prospective cross-sectional study. METHODS: The study was
      performed on 252 consecutive normal singleton pregnancies from 19 weeks of
      gestation until term, using transabdominal high-resolution ultrasound techniques.
      The sternal length, as well as the number of ossification centers at each
      gestational age, were recorded. RESULTS: The first occasion at which a fetal
      human sternum could be visualized with two to three ossification centers was at
      19 weeks' gestational age. The fifth ossification center was first visualized at
      29 weeks' gestation. The mean +/- SE of sternal length varied from 15 +/- 0.98 mm
      (95% confidence interval (CI) 12.79-17.21) at 19-20 weeks, to 36.50 +/- 0.29 mm
      (95% CI 35.58-37.42) at 37-38 weeks' gestation. Sternal length as a function of
      gestational age was expressed by the regression equation: sternal length (mm) = 
      11.06 + 1.39 x gestational age (weeks). The correlation coefficient, r = 0.924
      for sternal length, was found to be highly statistically significant (p <
      0.0001). CONCLUSIONS: The presented data offer normative measurements of the
      fetal sternum which may be helpful in the prenatal diagnosis of congenital
      syndromes that include, among other manifestations, abnormalities of sternal
      development.

PMID- 10204209
TI  - Early prenatal diagnosis of cord entanglement in monoamniotic multiple
      pregnancies.
AB  - OBJECTIVES: Cord entanglement is a severe complication in monoamniotic multiple
      pregnancies. Three cases were reviewed to determine how early ultrasound
      diagnosis might improve counselling and management. METHODS: In two monoamniotic
      twin and one dichorionic diamniotic triplet pregnancies, cord entanglement was
      detected between 10 and 18 gestational weeks by color Doppler and pulsed Doppler
      velocimetry. Pregnancies were followed up on a weekly basis with special
      observation of fetal behavior and use of color Doppler velocimetry. RESULTS: In
      Case 1, a monoamniotic twin pregnancy with cord entanglement close to the
      umbilical insertions was diagnosed at 10 weeks. Longitudinal follow-up showed
      intrauterine death of both twins at 15 weeks. In Case 2, entanglement of the
      umbilical cords of two monoamniotic triplets within a dichorionic diamniotic
      triplet pregnancy was diagnosed at 10 weeks. The pregnancy continued uneventfully
      until 35 weeks when cord entanglement was confirmed at Cesarean section. All
      triplets have since developed normally. In Case 3, monoamniotic twins were
      diagnosed at 18 weeks. Color Doppler detected side-by-side insertion of the
      umbilical cords and Doppler velocimetry suggested an entanglement at the
      chorionic plate. The pregnancy was complicated by polyhydramnios. Cesarean
      section at 36 weeks confirmed cord entanglement at the chorionic plate. Postnatal
      computer angiography and morphological examination of the placenta showed the
      presence of superficial artery-to-artery and vein-to-vein anastomoses and of deep
      arteriovenous shunts. The development of the twins was uneventful. CONCLUSIONS:
      Diagnosis of cord entanglement is feasible early in gestation. Future protocols
      are proposed to document the gestational age at detection, the location, and the
      Doppler flow patterns and to facilitate the assessment of short- and long-term
      development.

PMID- 10204211
TI  - Fetal pulmonary venous flow into the left atrium relative to diastolic and
      systolic cardiac time intervals.
AB  - OBJECTIVE: To establish the nature and gestational age dependency of the
      pulmonary venous flow velocity pattern into the left atrium relative to systolic
      and diastolic phases of the cardiac cycle. DESIGN: This was a cross-sectional
      study of Doppler measurements of fetal pulmonary venous inflow velocities, which
      were correlated with simultaneous recordings of transmitral and aortic flow
      velocity waveforms based on an equal cardiac cycle length (+/- 5%). RESULTS:
      Successful recordings were obtained in 28 out of 60 (47%) normal singleton
      pregnancies at 20-36 weeks of gestation. Reproducibility of waveform analysis of
      the various phases of the cardiac cycle was satisfactory, within-patient variance
      ranging between 1.7% and 6.5%. A statistically significant increase (p < 0.05) in
      pulmonary venous time average velocity and velocity integral with advancing
      gestational age was established. A statistically significant increase (p < 0.05)
      of the pulmonary flow velocity integral was also found when related to each of
      the systolic and diastolic segments of the cardiac cycle, with the exception of
      isovolemic relaxation time. The duration of each of the diastolic and systolic
      segments of the cardiac cycle, as well as the pulmonary venous velocity integral
      expressed as a percentage of the cardiac cycle, remained constant with advancing
      gestational age. CONCLUSIONS: The second half of pregnancy is characterized by
      pulmonary venous inflow into the left atrium throughout the cardiac cycle.
      Pulmonary venous inflow into the left atrium occurs predominantly during the
      filling and ejection phases of the cardiac cycle. Absolute cardiac diastolic and
      systolic time intervals as well as the percentage distribution of pulmonary
      venous flow velocity integrals between these cardiac time intervals remain
      unchanged with advancing gestational age.

PMID- 10204212
TI  - The 'Mickey Mouse' sign and the diagnosis of anencephaly in early pregnancy.
AB  - OBJECTIVES: To assess the sonographic screening for anencephaly in the first
      trimester in a low-risk obstetric population. METHODS: Since 1994, 5388 women
      attended our clinic for a first-trimester scan (11-14 weeks of gestation) and
      screening for structural and chromosomal abnormalities. The patients underwent
      transabdominal scanning, and transvaginal scanning if necessary. RESULTS: The
      ultrasonographic appearances of anencephaly in the first trimester are different
      from the familiar second-trimester signs. The cerebral hemispheres are present
      and exposed to the surrounding amniotic fluid. The ultrasound appearances in the
      coronal section of the head are best described as 'Mickey Mouse face'. There were
      six cases of anencephaly (incidence 1.1:1000). All cases were diagnosed in the
      first trimester and five demonstrated this sign. There were no false-positive
      diagnoses. The crown-rump length was significantly reduced in all affected
      fetuses. CONCLUSION: First-trimester ultrasonographic diagnosis of anencephaly is
      accurate, but sonographers should be familiar with the ultrasound appearances
      that are different from those in the second trimester.

PMID- 10204213
TI  - Definitive diagnosis of intestinal volvulus in utero.
AB  - Midgut volvulus with or without intestinal malrotation can occur in fetal life.
      Several reports have described congenital midgut volvulus showing non-specific
      sonographic findings of intestinal obstruction and perforation in utero. None of
      the previously reported cases, however, were definitively diagnosed as midgut
      volvulus by fetal sonography. We report two cases both exhibiting the sonographic
      'whirlpool' sign, in utero. Color Doppler interrogation provided a clue to the
      viability of the involved intestinal segment.

PMID- 10204214
TI  - Abnormal ductus venosus blood flow: a clue to umbilical cord complication.
AB  - We report a case of umbilical cord complication causing, fetal hypoxemia and
      acidemia. At 30 weeks of gestation, the patient was referred because of slightly
      increased amniotic fluid volume and a non-reactive cardiotocogram. Biometry was
      appropriate for gestational age. Umbilical artery and fetal aortic Doppler
      findings were normal, whereas diastolic blood flow velocities in the middle
      cerebral artery were increased and the ductus venosus showed severely abnormal
      flow velocity waveforms with reversal of flow during atrial contraction. Since
      other reasons for fetal hypoxemia could be excluded, careful examination of the
      umbilical cord was performed. Traction of the hypercoiled umbilical cord due to
      its course around the fetal neck and shoulders was suspected. Cesarean section
      confirmed the sonographic findings and fetal blood gases revealed fetal acidemia.
      This case indicates that investigation of fetal venous blood flow may also help
      to identify fetal jeopardy due to reasons other than increased placental vascular
      resistance.

PMID- 10204215
TI  - Congenital hernia of the abdominal wall: a differential diagnosis of fetal
      abdominal wall defects.
AB  - A 28-year-old woman was referred at 33 weeks of gestation with suspected fetal
      intestinal atresia. Sonography showed a large extra-abdominal mass on the right
      of the normal umbilical cord insertion. Following Cesarean section at 36 weeks
      and immediate surgical treatment, the malformation was not definable either as an
      omphalocele or as gastroschisis. This reported case involves a previously
      undocumented malformation of the fetal abdominal wall described as a 'hernia' of
      the fetal abdominal wall.

PMID- 10204216
TI  - Prenatal sonographic features of embryonal rhabdomyosarcoma.
AB  - We describe a case of fetal rhabdomyosarcoma detected during the third trimester
      of pregnancy by prenatal sonography. At 33 weeks' gestation, sonography performed
      because of suspected polyhydramnios showed a solid mass of 120 x 54 mm arising
      from the anterior wall of the fetal thoracic cage. Another mass within the left
      maxillary area which originated from the left orbital floor was also detected. In
      the abdomen, there were multiple round masses in and around the liver. As the
      previous scan at 28 weeks had appeared normal, the multiple masses which became
      visible and enlarged rapidly in different locations led us to believe that there
      was fetal cancer. The most likely diagnosis was rhabdomyosarcoma (which was later
      confirmed), because it is the most prevalent soft-tissue tumor in children and
      may develop within or outside muscle anywhere in the body and at any age. Two
      other reported cases which were detected by prenatal ultrasound examination are
      also discussed.

PMID- 10204218
TI  - Antenatal sonographic features of cri-du-chat syndrome.

PMID- 10204217
TI  - Prenatal sonographic features of spondylocostal dysostosis and diaphragmatic
      hernia in the first trimester.
AB  - Spondylocostal dysostosis is a congenital disorder characterized by multiple
      malformations of the vertebrae and ribs. We describe the sonographic features of
      an affected fetus at 12 and 14 weeks of gestation. The fetus had thoracic
      scoliosis, multiple vertebral and rib malformations and a grossly dilated stomach
      that had herniated into the chest through a left-sided diaphragmatic hernia. The
      stomach spanned the whole length of the fetal trunk.

PMID- 10204219
TI  - Prenatal diagnosis of fetal ambiguous gender using three-dimensional sonography.

PMID- 10204220
TI  - Adjusting the risk for trisomy 21 using multiple sonographic markers.

PMID- 10204221
TI  - E coli O157 food poisoning outbreak linked to milk.

PMID- 10204222
TI  - Subconjunctival haemorrhages in neonatal thoroughbred foals.
AB  - A survey of 169 neonatal thoroughbred foals revealed that 8.3 per cent had
      subconjunctival haemorrhages, but there was no indication of a relationship
      between retinal and subconjunctival haemorrhages. The haemorrhages were not
      related to any abnormality of the foals and there was no sex or eye
      predisposition. In most cases the haemorrhages were fresh and red, occurred
      mainly dorsally or dorsonasally and extended up to the limbus; they resolved
      completely within four to 10 days, depending on their initial severity and
      extent. They had no effect on the foals' vision in the short or long term. The
      incidence of subconjunctival haemorrhages was associated with foaling category,
      multiparity and country of birth.

PMID- 10204223
TI  - Salmonella pullorum in the common pheasant (Phasianus colchicus).
AB  - In 1996, pullorum disease due to Salmonella enterica serovar Gallinarum biovar
      pullorum (Salmonella pullorum) was diagnosed in pheasants on a gamebird rearing
      enterprise in south-west Scotland. The gross pathology and bacteriological
      findings are described, as are the results of screening for S pullorum on the
      site in 1997. The causal organism was readily isolated from the lung, liver, yolk
      sac and heart blood on direct culture, but less readily from the digestive tract
      or by the use of selective media. The bacteria recovered from the pheasants were
      identified as S pullorum phage type 7, a phage type previously associated with
      pheasants rather than domestic fowl, and the organisms were most probably
      introduced to the site by the movement of carrier pheasants.

PMID- 10204224
TI  - Risk factors associated with the seroprevalence of leptospirosis among students
      at the veterinary school of Zaragoza University.
AB  - The prevalence and risk factors associated with leptospirosis were studied in
      veterinary students in Zaragoza. Sera were collected at the beginning and end of
      the academic year 1994 to 1995 and were tested by ELISA against a pool of
      Leptospira interrogans serovars bratislava, canicola, grippotyphosa, hardjo,
      icterohaemorrhagiae and pomona antigens. At the beginning of the study the
      prevalence was 8.14 per cent and at the end it was 11.4 per cent. The incidence
      of the disease during the study was 0.0394. Risk factors associated with
      leptospirosis included: taking the course specialising in food inspection and
      technology, on-farm work, contact with pets in general, and particularly
      carnivores, and contact with animal traders. The symptoms associated with the
      disease were myalgia and fever, and the treatment of the symptoms provided some
      protection.

PMID- 10204225
TI  - Limited detection of sternal bone marrow infectivity in the clinical phase of
      experimental bovine spongiform encephalopathy (BSE).

PMID- 10204226
TI  - Rupture of the gracilis muscle in Iberian pigs at slaughter.

PMID- 10204227
TI  - Outbreak of coenurosis (Taenia species) in anglonubian goats in the Sultanate of
      Oman.

PMID- 10204228
TI  - Wing clipping in psittacine birds.

PMID- 10204230
TI  - 'Surprised' buffalo syndrome.

PMID- 10204229
TI  - Serological evidence for a 793/B related avian infectious bronchitis virus in
      India.

PMID- 10204231
TI  - Artificial insemination survey.

PMID- 10204232
TI  - Biodegradation of azo dyes by the yeast Candida zeylanoides in batch aerated
      cultures.
AB  - A number of simple azo dyes was degraded in liquid aerated batch cultures by a
      strain of the yeast Candida zeylanoides. The standard decolorization medium
      contained glucose as a carbon and energy source, and its pH was either controlled
      to 5.0-5.2, or allowed to decrease to 3.2-2.8, in the course of microorganism
      growth. The extent of colour removal in the culture medium was assessed through
      the decrease in dye absorbance of the supernatants. The extent of colour removal
      ranged from 44 to 90%, after 7 days, for 5 out of 6 dyes studied in shaked
      cultures, without pH control, and from 46 to 67%, after 22 hours, for 6 out of 8
      dyes in batch experiments, at controlled pH.

PMID- 10204233
TI  - Polychlorinated dibenzo-p-dioxins and related compounds in breast milk of
      Japanese primiparas and multiparas.
AB  - We analyzed polychlorinated dibenzo-p-dioxins and related compounds in the breast
      milk of primiparas and multiparas, and estimated the levels transferred to
      newborns by breast milk in Western Japan. 2,3,7,8-TeCDD equivalents (TEQ) of the
      chemicals in primiparas decreased slightly from 1994 to 1996. In particular,
      decreases of the TEQs of total PCDDs and total coplanar PCBs were higher than
      that of total PCDFs. In 2,3,7,8-TeCDD, 1,2,3,7,8-PeCDD, 1,2,3,6,7,8-HxCDD,
      1,2,3,7,8,9-HxCDD, 2,3,4,7,8-PeCDF, 1,2,3,6,7,8-HxCDF, 3,3',4,4',5-PeCB and
      3,3',4,4',5,5'-HxCB concentrations, those in the breast milk of multiparas were
      significantly lower than those in the breast milk of primiparas (p < 0.05, lipid
      basis). Based on the assumption that newborns ingest 120 g of breast milk per kg
      body weight per day, the amounts converted to TEQ values were 121 pg/kg/day
      (primiparas) and 97.2 pg/kg/day (multiparas).

PMID- 10204234
TI  - Dioxin and dibenzofuran concentrations in adipose tissue of a general population
      from Tarragona, Spain.
AB  - Polychlorinated dibenzo-p-dioxin (PCDD) and polychlorinated dibenzofuran (PCDF)
      levels were determined in adipose tissue of 15 autopsied subjects who at the time
      of death had lived in the city of Tarragona (Catalonia, Spain) and surroundings
      during at least the last 10 years. PCDD/F concentrations ranged between 13.37 and
      69.37 ng I-TEQ/kg fat, with mean and median values of 30.98 and 26.30 ng I-TEQ/kg
      fat, respectively. PCDD/F concentrations were higher (p < 0.01) in women (mean
      value: 44.95 ng I-TEQ/kg fat) than in men (mean value: 24.00 ng I-TEQ/kg fat).
      Although individuals living in industrial areas showed higher PCDD/F levels than
      those living Tarragona downtown the difference was not statistically significant.
      When Principal Component Analysis was applied to the concentrations of PCDD/Fs
      found in the 15 adipose tissue samples together with those found in 20 blood
      samples collected in a previous study, a single two-dimensional model was
      obtained, which would explain 62.9% of the variance in the data. The PCDD/F
      concentrations in adipose tissue found in the current study are of the same order
      of magnitude than those reported for most industrialized countries.

PMID- 10204235
TI  - In-vitro study of interaction between photooxidation and biodegradation of 2
      methylphenanthrene by Sphingomonas SP. 2MPII.
AB  - This work reports a study of interactions between reactions of photooxidation and
      reactions of bacterial degradation of an alkylated polyaromatic hydrocarbon (2
      methylphenanthrene). Bacterial growth was carried out using artificial sunlight
      as light source. Among the various products detected, the major product was
      identified as the 2-methylphenanthrene aldehyde. Sunlight allows accelerated
      elimination of the substrate. This enhancement of the biodegradation rate of 2
      methylphenanthrene is due to the use of assimilable photoproducts by the
      bacterium.

PMID- 10204236
TI  - Time trends in the concentrations of lead in wet precipitation from rural and
      urban sites in Austria.
AB  - Trend and time series analysis of concentrations of lead in wet precipitation at
      different rural and urban sampling sites in Austria, collected during intervals
      of 6-12 years (between 1984 and 1995) is performed. A substantial decrease of the
      lead concentrations for all sites in consideration is observed similar to
      observations in Germany, Sweden and North sea and western Atlantic regions.
      Reductions in rural sites between 60 and 80% in 10 years and around 90% in 10
      years in urban areas are found. This trend correlates with the reduction of lead
      emissions from combustion of gasoline. The seasonal deconvolution model of the
      data set reveals a typical seasonality with lead concentration peaks in summer
      and spring for the rural sites and winter peaks for urban sites. The average
      annual lead concentration in the rural region for 1995 was 1.25 micrograms/l, in
      the urban region 2.25 micrograms/l.

PMID- 10204237
TI  - Anaerobic formation and degradation of toxic aromatic compounds in agricultural
      and communal sewage deposits.
AB  - Relatively high concentrations of phenol, p-cresol, phenylacetic acid and other
      aromatic compounds were found in agricultural and communal sewage deposits. These
      toxic aromatic compounds are products of the bacterial degradation of aromatic
      amino acids under anaerobic conditions. In laboratory experiments at 26 degrees C
      and under N2-atmosphere, the same aromatics were formed from the amino acid
      tyrosine and from gelatine in assays inoculated with sewage sludge. After
      exhaustion of tyrosine and gelatine, respectively, concentrations of the
      accumulated phenol and other aromatics remained stable for months, i.e., phenol,
      p-cresol, phenylacetic acid etc. are dead-end products of the bacterial
      metabolism under these conditions. After addition of sodium nitrate the aromatic
      compounds are metabolically decomposed by denitrification within weeks.

PMID- 10204238
TI  - Quantities of bisphenol a leached from plastic waste samples.
AB  - To quantify the leaching of bisphenol A into water, various samples of plastic
      waste were cut into small pieces, soaked in water for two weeks at room
      temperature in the dark, and the concentration of bisphenol A in the water
      determined by gas chromatography/mass spectrometry (GC/MS). The amount of
      bisphenol A leached from the plastic wastes ranged from undetectable to 139
      micrograms/g. The detection limit was 2 ng/g when 100 g of plastic waste was
      used. Polyvinyl chloride products yielded the highest concentrations because
      bisphenol A is used in its manufacture as a stabilizer.

PMID- 10204239
TI  - Comparative study of methodologies for the analysis of PCDDs and PDCFs in
      powdered full-fat milk. PCB, PCDD and PCDF levels in commercial samples from
      Spain.
AB  - Feasibility of two different extraction methods involving solid-liquid extraction
      and Soxhlet extraction, previously used for the determination of lipid contents
      and PCB levels on powdered full-fat milk, are now examined for simultaneous
      PCDD/F analysis. The results of this study are consistent with those found for
      PCBs. The solid-liquid procedure provides the most efficient extraction of both
      labelled spiked and endogenous PCDD/Fs with the lowest variability. The average
      recoveries were 101% (R.S.D. = 6.9%) for 13C12-2,3,7,8-TCDD and 95% (R.S.D. =
      11%) for 13C12-1,2,3,4,7,8-HxCDD. The R.S.D.s for endogenous 2,3,7,8-PCDD/Fs were
      in the 9.3-25% range. In addition, this methodology simplified the subsequent
      clean-up step as it allowed a semi-selective extraction of the apolar lipids from
      the milk. The proposed method was applied to simultaneous PCB and PCDD/F analyses
      in different brands of powdered full-fat milks commercially available in Spain.
      In all cases, very similar PCB and PCDD/F levels were found. Differences among
      batches from the same manufacturer were even lower. The total i-TEQ average for
      PCDDs and PCDFs in the 22 powdered full-fat milk samples analysed was 1.87 pg/g
      fat basis. This value was similar to those found in cow's milk from other
      European countries.

PMID- 10204240
TI  - Evaluation of pectin binding of heavy metal ions in aqueous solutions.
AB  - Evaluation of adsorption performance of several industrially manufactured pectins
      towards some toxic heavy metals was carried out. Adsorption isotherms for
      divalent cations in simulant aqueous solutions were measured and corresponding
      distribution coefficients were calculated. The following selectivity sequences we
      found for pectins: Pb2+ >> Cu2+ > Co2+ > Ni2+ >> Zn2+ > Cd2+. It was shown that a
      beet pectin exhibits a high affinity for Pb2+ and Cu2+ ions, an apple pectin for
      Co2+ ion and a citrus pectin for Ni2+ ion. The binding properties of all pectins
      towards Zn2+ and Cd2+ ions are extremely poor. The quantitative data on
      adsorption performance of pectins suggest their applicability as food additives
      or remedies for efficient removal of Pb2+, Cu2+, Co2+, and Ni2+ ions from
      different biological systems, including human and animal organisms.

PMID- 10204241
TI  - Tissue distribution of planar and non-planar chlorobiphenyls, 4,4'-DDE and
      hexachlorobenzene in sheep and lambs.
AB  - The bioconcentration and distribution pattern of individual PCB congeners (IUPAC
      Nos: -54, -80, -155 and -169) and organochlorine pesticides (HCB and 4,4'-DDE) in
      blood, adipose tissue, liver and brain were examined in sheep two months after
      administration and in their offspring continuously exposed during the two months
      lactation period. Analyses were performed by high resolution gas chromatography.
      The levels of individual organochlorines varied significantly between tissues;
      the tissue/blood ratio (on a fat basis) varied by two orders of magnitude for
      individual congeners. The bioconcentration of the toxic planar PCB-169 congener
      was the highest in the liver and the lowest in the brain of the sheep.

PMID- 10204242
TI  - Volatility of propoxur from different surface materials commonly found in homes.
AB  - The purpose of this study was to determine the volatilization rates of propoxur
      from different surface materials commonly found in homes, and to conduct field
      measurements under ventilated and non-ventilated conditions. Since it is known
      that temperature, humidity and constant air flow most significantly affect
      volatility, various surface materials were sprayed using a constant amount of
      propoxur under the controlled conditions of an exposure chamber. Acetonitrile was
      used to desorb both XAD-2 resin that collected airborne propoxur and surface
      materials containing propoxur residue. HPLC was used to analyze propoxur
      concentrations. Based on multiple regression models, temperature most
      significantly affected volatility, followed by humidity. Volatilization rates of
      propoxur were highest from quartz surfaces and lowest from glass. Interaction was
      most readily found on glass surfaces based on humidity-air flow and humidity
      temperature factors. In field applications, propoxur was sprayed in a room under
      two conditions with ventilation and without in order to measure the
      concentrations of propoxur in the air and on a quartz surface. Findings showed
      both airborne and settled concentrations peaked after a half hour then decreased
      under both conditions, both more sharply in the ventilated room. Under both
      conditions, no propoxur was detected on the quartz surface after three and a half
      hours but airborne concentrations remained detectable after thirty-three and one
      half hours. We conclude that to maintain good air quality, ventilation is
      important and special care must be taken when spraying insecticides on different
      surfaces.

PMID- 10204243
TI  - Electron capture dissociation of substance P using a commercially available
      Fourier transform ion cyclotron resonance mass spectrometer.
AB  - Electron capture dissociation of the peptide Substance P is reported for the
      first time, with an unmodified, commercially available Fourier transform ion
      cyclotron resonance (FTICR) mass spectrometer. The fragmentation pattern is
      compared with that obtained with collisionally induced dissociation of the ions
      in the electrospray ion source, and note that electron capture dissociation gives
      a more easily interpreted spectrum, showing mainly C-fragments. With the
      exception of the proline residues, which require cleavage of two chemical bonds,
      we observe all C-fragmental we find the bias voltage of the electron gun not to
      be very critical.

PMID- 10204244
TI  - Quantitative analysis of pethidine using liquid secondary ion and tandem mass
      spectrometry.
AB  - A method for the quantatitive determination of pethidine in human urine by liquid
      secondary ion and tandem mass spectrometry is presented. Quantification was
      carried out by using ketamine as internal standard. It was found that the
      collision-induced dissociation (CID) spectrum of the [M + H]+ ion of pethidine
      exhibited a prominent daughter ion at m/z 220 and ketamine also yielded the same
      daughter ion at m/z 220. For ((quadrupole)) quantitative analysis, the first
      quadrupole mass filter was set to transmit m/z 220 and a narrow-range magnet scan
      yielded a spectrum of parents, including m/z 238 and 248, correspending to
      ketamine and pethidine, respectively.

PMID- 10204245
TI  - Confirmation of avermectin residues in food matrices with negative-ion
      atmospheric pressure chemical ionization liquid chromatography/mass spectrometry.
AB  - A multi-residue LC/MS method has been developed to confirm avermectin drug
      residues in several food matrices. Ivermectin (IVR), doramectin (DOR),
      eprinomectin (EPR) and moxidectin (MOX) are confirmed using atmospheric pressure
      chemical ionization (APCI) with negative ion detection and selected ion
      monitoring of three to four ions for each compound. The drug residues are
      extracted from tissue or milk using previously published procedures. IVR and DOR
      are confirmed at 20 ppb levels in fortified salmon muscle; IVR is also confirmed
      in tissue from salmon dosed with the drug. Residues of DOR, IVR, and EPR are
      confirmed in fortified milk at the 20 ppb level and in fortified beef liver at 40
      ppb. Residues of MOX can also be confirmed in these matrices, but at slightly
      higher levels (40-80 ppb).

PMID- 10204246
TI  - Analysis of metallothioneins by means of capillary electrophoresis coupled to
      electrospray mass spectrometry with sheathless interfacing.
AB  - Capillary electrophoresis (CE) coupled to electrospray mass spectrometry via
      sheathless interfacing has been applied to the analysis of mammalian
      metallothionein (MT) extracts. In a rabbit-liver extract, four (MT-2C, MT-2A, MT
      2D and MT-2E) out of six known MT sub-isoforms were unambiguously identified
      under three CE-resolved peaks. A fourth peak was found to contain MT-1A and/or MT
      2B, whose molecular masses differ by only 1 Da. Traces of non-N-acetylated MT-2D
      and MT-2E were observed in a fifth, minor peak. In a rat-liver extract, both MT-1
      and MT-2 were resolved and identified. Non-N-acetylated MT-2 was also identified
      in a resolved, minor peak. Minimum detectable amounts of MTs have been estimated
      to be approximately 0.6 fmol per sub-isoform.

PMID- 10204247
TI  - Fragmentation pathways of selectively labeled uropranolol using electrospray
      ionization on an ion trap mass spectrometer and comparison with ions formed by
      electron impact.
AB  - Propranolol, deuterium- and 18O-labeled propranolol and related compounds were
      analyzed using an ion trap mass spectrometer equipped with a modified Finnigan
      API electrospray interface. Sequential product ion (MSn) experiments were used to
      elucidate fragmentation pathways for these compounds. The observed ions were
      compared to those observed under electron impact (EI) conditions. The
      electrospray ionization (ESI) ion trap spectra, as well as the EI spectra, afford
      useful information to allow assignments of most product ions, many of which
      retain portions of the aliphatic three-carbon side chain.

PMID- 10204249
TI  - Irish Endocrine Society 23rd annual meeting. Waterford Surgical October Club and
      Surgical Section Royal Academy of Medicine Joint Surgical Symposium. Medical
      Research Cooperation in Ireland, North and South. Abstracts.

PMID- 10204248
TI  - Determination of the metal-binding cooperativity of wild-type and mutant
      calbindin D9K by electrospray ionization mass spectrometry.
AB  - Since the initial reports showing the ability of electrospray ionization mass
      spectrometry (ESI-MS) to study intact noncovalent biomolecular complexes, an
      increasing number of uses for this technique in studying biochemical systems is
      emerging. We have investigated the ability of ESI-MS to characterize the metal
      binding properties of calcium (Ca2+) binding proteins by studying the
      incorporation of Ca2+ and cadmium (Cd2+) into wild-type and mutant calbindin D9K.
      ESI-MS showed that wild-type calbindin D9K binds two Ca2+ ions with similar
      affinities while the binding of two Cd2+ ions is sequential, as is the binding of
      the two Ca2+ or Cd2+ ions to the N56A mutant of calbindin. The binding of Ca2+ to
      the wild-type protein was clearly seen to be cooperative. These results
      demonstrate the potential efficacy of ESI-MS to discriminate between cooperative
      and independent site metal binding to metalloproteins.

PMID- 10204250
TI  - Irish Society of Gastroenterology meeting. 20-21 November 1998. Abstracts.

PMID- 10204251
TI  - [National Days of Laboratory Medicine of Russia. Workshop on laboratory diagnosis
      and drug therapy. Moscow, September 9-11, 1998. Abstracts].

PMID- 10204253
TI  - Vitamins and Hormones, cumulative subject index, volumes 30-54.

PMID- 10204254
TI  - [Pro and con the trend to an increasing frequency of cesarean sections].
AB  - The trend of increasing the CS rate is based on the improvement of skill and
      safety of operation, broadened and not well defined indications, some
      demographic, anthropological and social changes during recent decades. Most
      authors stress on the patient's will and on the role of nonclinical factors
      including the physician's training/experience, financial and convenience
      incentives. At the same time the increasing CS rate can not achieve the expectant
      medical benefits as abrupt decrease of prenatal mortality and morbidity, or
      intranatal trauma for the newborn and the women. Efforts to reduce unnecessary CS
      should focus on identifying the appropriate clinical indications for CS and
      spread this information to physicians. The trial to calculate the optimal rate of
      CS based on the prenatal mortality and morbidity, on the rate of the complication
      during pregnancy and labor requiring CS or the magnitude of delivery trauma
      nowadays is unsatisfactory. To compare the CS rate between countries or regions
      and draw conclusions from this is inadequate as many medical and nonclinical
      variables take place in the decision to perform cesarean delivery.

PMID- 10204252
TI  - The Ulster Medical Journal index: volumes 1-64.

PMID- 10204255
TI  - [The obstetrical management of pregnant patients with spontaneous rupture of the
      fetal membranes after 37 weeks' gestation].
AB  - The purpose of the study was to analyze the obstetric management in pregnancies
      with spontaneous rupture of membranes (RM) after 37 w.g. and to find out is there
      a correlation between the cervical status and the pregnancy outcome. The study
      includes 66 primiparous women divided into two groups depending on the cervical
      status(CS) at admission: Group 1-44 patients with unfavourable cervix (PS < 4)
      according to the Bishop's original scoring system and Group 2-22 patients with
      favourable cervix (PS > 4). The delivery started spontaneously within the first 8
      hours after the RM in 59% of the pregnant women with favourable cervix compared
      to 50% of women with PS < 4. There is no significant difference in the mean
      duration of the latent period between group 1 and 2-6.3 and 6.2 hours,
      respectively. The mean duration of delivery was 14.08 hours in Group 1 compared
      to 14.03 hours in Group 2. 72.7% of the pregnant women in Group 1 had normal
      vaginal delivery compared to 86.44% of the patients in Group 2. There were 3
      newborn (one in Group 1 and 2 in Group 2) with signs of infection. There were no
      perinatal deaths. Postpartal endometritis was diagnosed in 2 of the patients with
      unfavourable cervix. There is no motivation to fear the development of ascendant
      infection in pregnancies with RM after 37 w.g. even if the time elapsed from the
      very beginning of the RM to the start of delivery is more than 24 hours. We
      favour both active and passive management of delivery in pregnancies with
      favourable cervix at the time of RM. We have to reevaluate the active approach in
      pregnancies with unfavourable cervix and ruptured membranes because of the higher
      incidence of operative deliveries because of non-progress of labour in these
      cases.

PMID- 10204256
TI  - [The effect of tobacco smoking on maternal weight gain and the neonatal results].
AB  - Our aim was to investigate the effects of smoking till term on maternal weight
      increase and on the foetus after delivery. The study is prospective and includes
      a group of 238 pregnant smokers consulted at the Antenatal clinics of the 3rd
      county polyclinic, Pleven. 115 of them smoked regularly until term at least 5
      cigarettes weekly (48.32%), while 123 stopped smoking prenatally (45.9%).
      Utilizing a special test these two groups were compared based on their pre
      delivery weight and the weight of their foetuses. RESULTS: The women who stopped
      smoking increased in weight with 16.6 kgs (SD-14.5), while those who smoked till
      term thrived with 13.2 kgs (SD-11.7) (Pt 0.001). This greater increase in
      maternal weight is connected with a 3.1 times more frequent delivery of babies
      weighing more than 4000 gr. All neonates with LBW were in the group of smokers,
      as well as those with foetal demise (perinatal deaths = 12.76%. CONCLUSION: In
      the studied group stoppage of smoking is connected with less risk of inadequate
      increase of weight, LBW and their foetuses more frequently weigh more than 4000
      gr.

PMID- 10204258
TI  - [The incidence and structure of congenital anomalies at the Maternity Home State
      University Hospital, Sofia in the period of 1992-1996].
AB  - This is a retrospective study on the dynamics of inborn malformations in
      University Hospital of Obstetrics and Gynaecology 'Maichin Dom', Sofia for a five
      years-long period of time (1992-1996). The results show that the rate of inborn
      anomalies in the discussed period of time remains approximately the same, while
      there is an increase of the relative part of heavy and life-threatening
      malformations. They cause death of nearly half of term infants who die in the
      neonatal period. These facts lead to the conclusion that to decrease perinatal
      and neonatal mortality, early and exact prenatal diagnosis of inborn
      malformations is absolutely necessary.

PMID- 10204257
TI  - [The use of Curosurf with premature infants--the prevention or treatment of the
      neonatal RDS].
AB  - A randomized clinical prospective study is carried out aiming to compare
      prophylaxis with Curosurf versus rescue treatment. 28 inborn VLBW I are included:
      17 received Curosurf as prophylaxis and 11 controls, who received rescue
      treatment if indicated. Both groups are similar regarding mean body weight, mean
      gestational age, dosage of Curosurf, etc. Results underwent statistic analysis.
      Data from the study shows better effect from prophylaxis with Curosurf: smaller
      number of babies developed RDS and especially RDS grade III-IV (subsequently less
      babies needed a second dose of Curosurf); higher PaO2/FiO2 ratio; reduced
      duration of artificial ventilation and of oxygen therapy; reduced incidence of
      BPD. Results do not show statistically significant difference, but a tendency for
      ft. As a conclusion: prophylaxis with Curosurf leads to a decrease in the
      incidence and severity of RDS and to reduced duration of ventilation support and
      oxygen therapy.

PMID- 10204259
TI  - [Postnatal screening for congenital anomalies--the possibility of detecting
      families at high genetic risk].
AB  - The aim of the study was to present out experience with the registration of
      congenital anomalies (CA) and to assess the effect of the preventive genetic
      consultative activities in affected families. In the period 1990-1996, 19174
      infants born or hospitalized at the Clinic of Obstetrics, Pleven were screened
      for CA, showing frequency of 26.1%. Structural analysis of the CA is presented.
      226 out of 500 (45%) families with and affected child were consulted by a
      geneticist. Data an prenatal diagnosis (PD) offered to 142 families at high risk
      and their reproductive decision are submitted. The low rate of families made use
      of invasive PD is pointed out; the real benefits of ultrasonography as a
      screening test for detection of fetal anomalies has been recommended.

PMID- 10204260
TI  - [The dynamics of the alpha 1-protease inhibitor and alpha 2-macroglobulin in very
      low-birth-weight newborns].
AB  - OBJECTIVES: The purpose is to improve the neonatal outcome and to prognosticate
      the risk for developing respiratory problems. For that reason the serum
      concentrations of 1-inhibitor of proteolysis (alpha 1-IP) and 2-macroglobuline
      (alpha 2-M) at very low birth weight infants (< 1500 g) were investigated. STUDY
      DESIGN: The research is prospective and it is made for the period from January
      1st 1995 up to December 31st 1995.17 very low birth weight infants (VLBWI) were
      the main group and 19 full term babies were the control group. The method of so
      called 'rocket' immunoelectrophoresis was used (this method was an innovation of
      D. Nankova [correction of P. Nancova], V. Kamenova, 1990). Blood was taken from
      babies just after delivery and at 3rd-4th day. Alternative, variantative and
      graphic analyses were used. RESULTS: The average value of alpha 1-IP for VLBWI
      was 2.036 g/l (SD +/- 0.44 g/l) for the 1st test and 2.31 g/l (SD +/- 0.41 g/l)
      for the 2nd test. The average value of the healthy full term babies was 2.055 g/l
      (SD +/- 0.37 g/l) for both tests. The lowest values of alpha 1-IP (from 0.6 g/l
      to 1.9 g/l) were in babies with genetic and respiratory problems. The main group
      had an average value of alpha 2-M 3.44 g/l (SD +/- 0.92 g/l) for the 1st test and
      a little higher values for the 2nd test -4.99 g/l (SD +/- 0.72 g/l) with
      significant differences p(t) < 0.0001. The lower levels of alpha 2-M were founded
      in VLBWI and they were significant for decreased protective reactions against
      pathologic micro-organisms. CONCLUSIONS: Control of serum concentrations of alpha
      1-IP and alpha 2-M are an additional diagnostic and prognostic criterion in VLBWI
      for developing respiratory problems.

PMID- 10204261
TI  - [Detrusor instability--an important but underestimated factor in urinary
      incontinence in women].
AB  - 157 consecutive female patients complaining of urinary incontinence were studied
      by history and urodynamics. 21 of them (13.4%) demonstrated urge-incontinence due
      to severe detrusor instability, 20 (12.7%) showed mixed (both urge and stress)
      incontinence, 14 (9%) only detrusor instability and 12 (7.6%)--stress
      incontinence accompanied by detrusor instability. Pure stress incontinence was
      diagnosed in 79 cases (50.3%) while 11 patients (7%) manifested no abnormality
      during the urodynamics. A total of 67 patients (42.7%) showed urodynamic evidence
      of detrusor overactivity. In 55 (35% of the studied subjects) it was the main
      urodynamic finding. The prevalence of detrusor instability was higher among those
      with recurrent incontinence and was the highest (60%) among the women with more
      than one previous operations. When urge incontinence was present it occurred at
      detrusor pressures lower than the maximum urethral closure pressure, which
      implies possible failure of the sphincteric mechanisms associated with detrusor
      instability. 14% of the women with detrusor instability did not report complaints
      typical for this disorder but had history of stress incontinence alone. The
      authors confirm the necessity of objective assessment of the lower urinary tract
      in all cases with history suspicious of detrusor instability as well as when
      surgical treatment for stress incontinence is planned.

PMID- 10204262
TI  - [The late results of the surgical treatment of stress urinary incontinence].
AB  - The severe stress urinary incontinence is a condition, which traumatize women
      psychology. Amongst numerous well-known operative techniques for treatment of the
      stress urinary incontinence authors apply the following ones: suprapubic
      colpouretherosuspension by Burch, colpouretherosuspension by Ratz, sling
      operation with synthetic stuff--Ampoxen. The evaluation of late results from the
      applied operative approaches in 30 patients displaced a long term overcome of
      stress incontinence. The authors emphasized that during clinical follow up of all
      cases in the course of 3 years the best results were obtained after application
      of suprapubic and sling methods. Our conclusion is that the choice of operative
      approach have to be individual and is in dependence with every clinical case. The
      postoperative outcome depends on the exactness of the operation.

PMID- 10204263
TI  - [Malignant degeneration in women operated on for endometriosis].
AB  - The endometriosis can undergo estrogen-dependent changes similar to endometrium
      and may carry a risk for developing hyperplasia and carcinoma during unopposed
      estrogen stimulation. We reviewed the existing literature to analyze the
      potential of malignancy arising from extraovarian endometriosis by estrogen
      stimulation. Our two cases are also discussed. According to our study there are
      21 cases published in the literature of malignant transformation of endometriosis
      after estrogen stimulation. The most common place for malignant trans formation
      is the vagina. The most common hystological type is adenocarcinoma in 13 cases.
      Our two cases were with adenocarcinoma and adenosquamous carcinoma. The incidence
      of malignant transformation of the endometriosis can not be estimated based upon
      these cases. There is a need for randomised clinical trials. CONCLUSIONS: The
      estrogen stimulation may lead to premalignant or malignant transformations of the
      residual foci of endometriosis. That is why addition of progestins to the
      estrogen substitutional therapy should be considered in women with endometriosis
      after total hysterectomy with oophorectomy, especially if a residual foci are
      present or suspected. With our study we think we can make more clear the way an
      endometriosis is transformed into a malignancy.

PMID- 10204264
TI  - [The volume of the surgical treatment and follow-up of patients with malignant
      ovarian tumors in the first stages].
AB  - From 1987 till 1997 110 patients with stage-I ovarian malignant tumors were
      treated and follow-up at the Department of Gynaecological Oncology, National
      Oncological Center. Papillifery-adenocarcinoma were in 40 cases, serous carcinoma
      were in 26 cases, mucinous carcinoma were in 15 cases, malignant granulosa cell
      tumor were in 14 cases, endometrioid carcinoma were in 6 cases, dysgerminoma were
      in 6 cases, Teilum's tumour were in 2 cases, and 1 case of ovary sarcoma were
      detected. Radical operated on the first operation were 69 patients (62.8%), and
      in 37 cases (33.6%) second operation for radicality were performed. In 4 cases
      only adnexectomy were done. In all cases post operative adjuvant chemotherapy
      were used. The patients were follow-up by tumour markers, sonography and CT.
      Follow-up period is from 5 months till 11 years. Alive were 80 patients (73%),
      and 30 patients (27%) were died. The patients with stage Ic and those nonradical
      operated in the first operation have worst prognosis then patients with stage Ia
      and stage Ib. The patients with ovarian tumours must be operated only in the
      hospitals with possibility of urgent hystological diagnosis for better prognosis
      in the cases of stage-I malignant ovarian tumours.

PMID- 10204265
TI  - [Combined diagnostic methods for women in the pre- and postmenopause].
AB  - During one-year period, 20 women with pre- and post-menopausal problems were
      investigated. The diagnostic examination included transvaginal sonography (TS),
      hysteroscopy with separative abrasion and histopathological examination. The data
      from the three diagnostic methods were compared. RESULTS: In 6 patients the
      endometrial thickness (ET) was lower than 8 mm. The hysteroscopic finding (HF)
      comprised in endometrial atrophy, confirmed also histologically. ET was higher
      than 8 mm in 14 patients, and the HF revealed endometrial polyps and endometrial
      hyperplasia. The hystological examination confirmed cystic endometrial
      hyperplasia in 4 cases, endometrial secretary phase in 5 cases, endometrial polyp
      in 3 cases and endometrial carcinoma in 2 cases. The authors accepted that the
      combination of 3 diagnostic methods of examination, applied in the described
      consequence, gave the possibility for precise diagnostic investigation and
      adequate treatment.

PMID- 10204266
TI  - [The structure and incidence of the basic causes of maternal mortality].
AB  - The author treats by the presented scientific publication the structure and
      frequency of causes for maternal mortality in particular countries and mainly in
      Bulgaria. Several structure types of maternal mortality are examined-
      "extragenital", "hemorrhagic", "septic". It has been proven through a close
      examination of the work of women's consultation cabinets with regard to maternal
      mortality that a considerable dependence and regularity is determined due to the
      insufficient coverage of women from housing complexes (only 24.9% have 6-14
      visits). For 1995 dead pregnant women, women in delivery and young mothers in
      particular regions are 0.1 for 1000 from 73,032 checked-up women. Only in Sofia
      and Montana region the mortality rate is 0.2 for 1000. For 1996 the mortality
      rate in the presented regions (see Table N1) for pregnant women, women in
      delivery and young mothers has increases to 7 (0.2 for 1000).

PMID- 10204267
TI  - [Disorders in sexual function following hysterectomy].
AB  - The authors aims to examine the sexual function among patients prior to
      hysterectomy. Four groups were examined: group one--total hysterectomy with
      bilateral adnexectomy; group two--total hysterectomy without adnexectomy; group
      three--supracervical hysterectomy with bilateral adnexectomy and group four-
      supracervical hysterectomy without adnexectomy. A questionnaire aimed at Learning
      the sexual function and psychologic state of the patients and more importantly
      the effects of the hysterectomy on then was passed out. From the completed
      questionnaires we found that the most affected group was the one of total
      hysterectomy with bilateral adnexectomy. In all respects sexual function is
      disturbed in this group. Least affected are patients in groups three and four. In
      some of them we even found a slight increase in sexual function, which is
      regarded compensatory for eliminating the infertility complex arising from
      surgery of the most important female organs.

PMID- 10204268
TI  - [The morphology of human spermatozoa--the norm and pathology].
AB  - The careful analysis of sperm morphology is an important part of routine semen
      examination. Although, there are different classification systems and methods for
      staining of the semen smears, the prognostic value of this assessment for man's
      fertility potential requests to be an obligatory part of semen analysis.
      Literally review shows that there are united attitude towards the significance of
      this semen parameter in vivo and in vitro. Most promising is development of
      intracytoplasmic sperm injection (ICSI) as the treatment of first choice in cases
      of severe teratozoospermia (for example round-headed spermatozoa). This suggests
      that sperm morphology may be important in spermatozoa-zone binding, penetration
      and spermatozoon-oocyte fusion, but fails to be of any "normality" once the
      spermatozoa reaches the cytoplasm of the oocyte.

PMID- 10204269
TI  - [The electron microscopic pathology of human spermatozoa].
AB  - About 8% of our patients reveal predominantly single abnormality-state, known
      like monomorphic teratozoospermy, which concerns round headed spermatozoa,
      amorphous heads, small heads, tapering heads, decapitated spermatozoa,
      middlepieces and tail defects. In the light of electron-microscopy study the
      quality and information exactness increases significantly in comparison to
      conventional semen analysis. Such kind of study, however is not acquitted in
      normal fertile men, although the finding some of the above mentioned defects, but
      with less frequency. The assessment of human semen quality must be complex and
      coordinately without depreciation of the other methods of semen analysis.

PMID- 10204270
TI  - [The loss of virginity and sexual activity in adolescence].
AB  - A questionnaire was filled in anonymously aiming at studying the motivation,
      conditions for defloration and sexual activity of a total of 96 girls aged 15-18
      from 4 schools in the town of Varna. It was established that 50% of them had had
      a sexual intercourse, in 77.1% the defloration occurred at the age of 16 or 17.
      82.3% report "love" as their main motive, 12.5% report to have done it "out of
      curiosity" and only in 7.2% it happened "by chance". 36.4% were prepared
      psychologically for the act of defloration. In 42% the coitus occurred at
      parties, 43.7% in the evenings or at night, 13.5% prefer the summer and 11.4% the
      spring season. About one third of the interviewed continued their sexual relation
      with their first partner who in 41.7% happened to be their steady boyfriend. The
      frequency of the sexual relation was reported to be once a week by 9.4% every day
      by 5.2% and 30.2% could not determine it. Contraceptives were reported to be used
      by 34.4%, 27.1% use condoms and 22.9% interrupt coitus. Recommendations for
      healthy sex during adolescence are based on the results obtained as well as
      literary data.

PMID- 10204271
TI  - [The monitoring of fetal status during birth. The current possibilities, problems
      and directions for improvement].

PMID- 10204272
TI  - [Anticonvulsive therapy in eclampsia--its current status].
AB  - Conflicting opinions on the adequate and appropriate anticonvulsive therapy for
      eclampsia stems from the fact that a lot of unclarity still exists as per the
      reasons for eclamptic seizures. The authors reviews current data from literature
      on the problem of anticonvulsive therapy for eclampsia and tries to clarify the
      uncertainties on the optimal approach for eclamptic seizures. Despite the fact
      that many neurologists in the U.S. as well as a great number of obstetricians in
      Europe are now sceptical about the anticonvulsive effect of magnesium sulphate
      and prefer other anticonvulsive agents, the parenteral application of magnesium
      is still the principal approach for eclampsia. There is a need however for a new
      strategy for prophylaxis and therapy of eclampsia. Which will lead to a
      significant reduction of the fatality rate in cases of grave preeclampsia
      eclampsia.

PMID- 10204273
TI  - [The screening and diagnosis of ovarian cancer].
AB  - The ovarian cancer represents important medico-social problem for our country due
      to its significant frequency (26.1%) and high mortality (9/1000) among the
      oncogynecological diseases. The aim of the present review was to discuss the
      methods--for diagnostics of the ovarian cancer trough analyzing the possibilities
      for their implementation as a screening in the clinical practice. It is pointed
      out, that the secondary prophylaxis for ovarian cancer has its place as a
      selective screening for women with high risk. The proposed scheme includes:
      gynecological and ultrasound checks up and CA-125 investigation every two year
      after twenty-five ages of the woman.

PMID- 10204274
TI  - [A rare case of a variant cervical polyp in adolescence].
AB  - The authors, stress on the importance of the examination of the vagina and the
      cervix in case of a mucous bleeding at adolescent girls. The following case is
      being introduced: after examination of a 16-year-old patient who had undergone a
      two-year treatment for a vaginal discharge, a bleeding polyp, the size of an egg
      and attached to a leg was found and extirpated. The histological examination read
      as "a myomatous polyp of the cervical canal with hemorrhagic necrosis". This case
      has been compared with the already published classes. The authors discuss some
      possibilities for differential diagnosis of the subjective symptoms and biopsy in
      adolescence. The conclusion is that gynecologists should use vaginoscopy as
      additional diagnostic method.

PMID- 10204275
TI  - [A new therapeutic approach in the treatment of genital chlamydial infections.
      Azithromycin (Sumamed)].
AB  - Azithromycin is a member of a new class of macrolides called azalydes. Although
      azithromycin resembles erythromycine there are significant differences in
      antibacterial activity and pharmacokinetic profile. Azithromycin is taken up by
      cells and the intracellular concentrations are significantly higher than serum
      concentrations. After a single oral dose of Ig, azithromycin has a long lasting
      effect--the tissue concentrations in the uterine and cervical tissues are kept
      above the minimal inhibitory concentration for Chlamydia trachomatis for more
      than 10 days. In order to achieve the maximal bioavailability and avoid side
      effects (gastrointestinal discomfort), azithromycin should be taken apart from
      meals (one hour before or two hours after meals). Azithromycin has no hepatotoxic
      potential and the possibility for drug interactions is not apparent. It is also
      recommended for use in pregnant women--FDA category B. A single oral dose of Ig
      azithromycin is the reasonable choice for the treatment of uncomplicated genital
      chlamydial infection.

PMID- 10204276
TI  - Symptom structure in obsessive-compulsive disorder: a confirmatory factor
      analytic study.
AB  - Although obsessive-compulsive disorder (OCD) has long been a unitary diagnosis,
      there is much recent interest in its potential heterogeneity, as manifested by
      symptom subgroups. This study evaluated existing models of symptom structure in a
      sample of 203 individuals with OCD. Using confirmatory factor analysis, we
      examined the ability of each model to account for two levels of data: a priori
      symptom groupings (second-order) and individual symptoms, identified by the Yale
      Brown Obsessive Compulsive Scale symptom checklist. Four models were examined: a
      single-factor, a two-factor (i.e., obsessions and compulsions), and two
      multidimensional models, comprising three and four factors. Adequate fit was
      found solely for the four-factor model--specifying obsessions/checking,
      symmetry/ordering, contamination/cleaning, and hoarding--but only at the second
      order level; it did not account for relationships among discrete symptoms.
      Parameter estimates showed within-factor heterogeneity, as well as overlap
      between factors, most notably the two representing checking and contamination
      related symptoms. The implications of these findings are discussed. Results
      provide evidence for the multidimensionality of OCD symptoms, but suggest that a
      comprehensive model has yet to be identified. They also point to the inadequacy
      of groupings based solely upon overt behavioural similarities (e.g., 'checking').
      Recommendations are made for future research.

PMID- 10204277
TI  - Effects of anxiety sensitivity on anxiety and pain during a cold pressor
      challenge in patients with panic disorder.
AB  - Fear of anxiety symptoms, or anxiety sensitivity (AS), has been extensively
      studied in anxiety disorders and more recently has been linked to other
      psychopathological conditions including pain. Asmundson and colleagues have
      suggested that AS may act as a risk factor for chronic pain and several studies
      have demonstrated an association between AS, avoidance behaviors and pain. The
      present study assessed whether AS levels would be predictive of pain and anxiety
      during a brief pain induction task. Clinical participants meeting DSM-IV criteria
      for panic disorder (n = 22) were age and sex matched with nonclinical controls (n
      = 22) and exposed to a 2-min cold pressor challenge. Diagnostic status and AS
      were significantly predictive of pain and anxiety during the cold pressor task.
      Moreover, AS appears to mediate the relationship between diagnostic status and
      pain. However, AS appears to be only indirectly associated with pain through its
      contribution to anxiety.

PMID- 10204278
TI  - Inflated perceptions of responsibility and obsessive-compulsive symptoms.
AB  - In Salkovskis' [Salkovskis, P. (1985). Obsessional-compulsive problems: a
      cognitive-behavioural analysis. Behaviour Research and Therapy, 28, 571-588;
      Salkovskis P. (1989) Cognitive-behavioural factors and the persistence of
      intrusive thoughts in obsessional problems. Behaviour Research and Therapy, 27,
      677-682] cognitive model for obsessive-compulsive disorder (OCD), inflated
      perception of responsibility is highlighted as the critical feature that
      maintains the disorder. In the current study, the relationship between
      responsibility and obsessive-compulsive (OC) symptoms was examined. Specifically,
      three measures of responsibility were evaluated for their psychometric
      properties. These measures were then used to test Salkovskis's model by examining
      the relationships among pervasive responsibility, automatic thoughts related to
      causing harm, and OC symptom severity. Findings provide partial support for the
      validity and reliability of the measures and for the model as a whole. Based on
      regression analyses, data support that pervasive responsibility significantly
      contributes to the prediction of OC symptoms. Furthermore, this relationship
      appears to be mediated by automatic thoughts related to causing harm in OCD
      contexts.

PMID- 10204279
TI  - Cross-cultural aspects of fears in African children and adolescents.
AB  - The purpose of this study was to compare level and type of fears in Nigerian and
      Kenyan children using the Fear Survey Schedule for Children, Revised (FSSC-R;
      [Ollendick, T.H. (1983). Reliability and validity of the Revised Fear Survey
      Schedule for Children (FSSC-R). Behaviour Research and Therapy, 21, 685-692]). A
      total of 852 males and females between the ages of 8 and 17 were surveyed.
      Results indicated that Nigerian children reported significantly higher total fear
      than Kenyan children and that scores from both countries were higher than those
      found in the United States, Australia and China. This suggests that the cultures
      of Kenya and Nigeria may share a common variable that makes reporting of fears
      greater than that reported by children of other world cultures. In addition,
      Christian children in both countries reported higher levels of fear on several
      factors than Muslim children, indicating that Islamic beliefs may encourage
      children to report less fear or to deal with their fears better than Christian
      beliefs. Finally, children between the ages of 8 and 12 reported greater fear of
      the unknown than children between 13 and 17 years of age. Overall, these findings
      suggest that important cultural, religious and age differences exist for levels
      of childhood fears reported in Nigeria and Kenya.

PMID- 10204280
TI  - Behavioral assessment of personality disorders.
AB  - This article examines the definition of personality disorders (PDs) from a
      functional analytical framework and discusses the potential utility of such a
      framework to account for behavioral tendencies associated with PD pathology. Also
      reviewed are specific behavioral assessment methods that can be employed in the
      assessment of PDs, and how information derived from these assessments may be
      linked to specific intervention strategies.

PMID- 10204281
TI  - Valuable, but not maximal: it's time behavior therapy attend to its behaviorism.
AB  - The field of behavior therapy is not in touch with itself in terms of its
      overarching behaviorism. Many erroneously consider its basic behaviorism to have
      been radical behaviorism and continue to look to develop behavior therapy
      (including behavior analysis and behavioral assessment) within that framework.
      But that approach turns out to be much less than maximal because there is a more
      advanced, better developed behaviorism within which to conduct and project the
      field. There is much that behavior therapy is not doing in practice and research
      because it is not making full use of that behaviorism foundation.

PMID- 10204282
TI  - The likely success of functional analysis tied to the DSM.
AB  - Nelson-Gray and Farmer argue that behavioral assessment and functional analysis
      may be beneficially applied to personality disorders (PDs). While this is a
      reasonable response to the largely non-behaviorally derived Diagnostic and
      Statistical Manual (DSM), it is not yet clear that grafting such theoretically
      incongruent elements will be viable. In essence, they argue that a syndromal
      classification system could serve a nomothetic role of guiding a functional,
      idiographic analysis. This is possible, but it seems unlikely that this process
      would remain in equilibrium, with no interactive effect of the functional
      analysis on the syndromes themselves. Yet the DSM system has shown itself to be
      surprisingly closed to a more functional approach, so the relationship between
      the DSM and functional analysis is not open in both directions. What is needed is
      a nomothetic level of analysis that is also functionally derived. The primary
      benefit of functional over syndromal categories is one of treatment utility, a
      concept that is itself surprisingly absent from the authors' otherwise
      comprehensive discussion of behavioral assessment.

PMID- 10204283
TI  - Functional analysis and response covariation in the assessment of personality
      disorders: a reply to Staats and to Bissett and Hayes.
AB  - In this reply to Bissett and Hayes (this issue) and Staats (this issue) we
      address critical comments in response to our initial proposal and highlight
      points of agreement. The overall thesis of our reply is that classification
      schemes based on nomothetic response covariation, such as DSM, complement, but do
      not substitute for, an idiographically-based functional analysis and behavioral
      assessment. In the context of our reply, we address the following primary
      concerns raised by Bissett, Hayes, and Staats: (a) we are essentially proposing
      the melding of two theoretically incongruent approaches, and that such a melding
      is inherently not viable or useful; (b) the behavior analytic approach cannot
      account for personality or psychological constructs; and (c) that categories
      based on topography do not have demonstrated treatment utility. We also discuss
      points of agreement with our respondents: (d) a theoretically-based descriptive
      classification system is required to ultimately advance clinical science, (e) the
      DSM personality disorder classification system, to remain viable, needs a
      stronger empirical base; and (f) that alternatives to DSM classification that
      more strongly emphasize behavioral principles are in need of development.

PMID- 10204284
TI  - Acute respiratory infections, and influenza vaccine for 1999/2000.

PMID- 10204285
TI  - Identifying and mapping community vulnerability.
AB  - Disaster vulnerability is socially constructed, i.e., it arises out of the social
      and economic circumstances of everyday living. Most often discussed from the
      perspective of developing nations, this article extends the argument using
      American demographic trends. Examples from recent disasters, Hurricane Andrew in
      particular, illustrate how certain categories of people, such as the poor, the
      elderly, women-headed households and recent residents, are at greater risk
      throughout the disaster response process. Knowledge of where these groups are
      concentrated within communities and the general nature of their circumstances is
      an important step towards effective emergency management. Emergency planners,
      policy-makers and responding organisations are encouraged to identify and locate
      high-risk sectors on Community Vulnerability Maps, integrating this information
      into GIS systems where feasible. Effective disaster management calls for
      aggressively involving these neighbourhoods and groups at all levels of planning
      and response, as well as mitigation efforts that address the root causes of
      vulnerability.

PMID- 10204286
TI  - Losses from the Northridge earthquake: disruption to high-technology industries
      in the Los Angeles Basin.
AB  - This study explores the relationship between industrial location geography,
      metropolitan patterns and earthquake disasters. Production losses from the 1994
      Northridge earthquake to the Los Angeles Basin's most important high-technology
      industrial sector are evaluated in the context of that area's polycentric
      metropolitan form. Locations for each one of the Los Angeles Basin's 1,126
      advanced electronics manufacturing establishments were identified and mapped,
      providing an indication of the patterns and clusters of the industry. An
      extensive survey of those establishments gathered information on disruptions from
      the Northridge earthquake. Production losses were then estimated, based on the
      sampled plants' lost workdays and the earthquake's distance-decay effects. A
      conservative estimate of total production losses to establishments in seven four
      digit SIC advanced electronics industrial groups placed their value at US$220.4
      million. Based on this estimate of losses, it is concluded that the Northridge
      earthquake's economic losses were much higher than initially anticipated.

PMID- 10204287
TI  - Landslides, risk and decision-making in Kinnaur District: bridging the gap
      between science and public opinion.
AB  - In November 1989 a major landslide destroyed the link road to the village of
      Sapni in Kinnaur District of Himachal Pradesh in the Indian Himalaya. Although
      aware of the risk of further landslide activity, the community has campaigned
      successfully for reconstruction of the road. Decisions of this kind take place at
      the local level, through village institutions and open debate, with good feedback
      between villages and district government authorities. In this way a balance is
      established between meeting more immediate needs (such as domestic water supply,
      irrigation, road access) and taking acceptable risks. Using the Sapni landslide
      as a case study, this paper explores the issue of 'acceptable risk', and looks at
      the existing strategy for risk and disaster reduction in the district.

PMID- 10204288
TI  - Typhoon hazards in the Shanghai area.
AB  - There are three major typhoon hazards that apply to the Shanghai area. First,
      galeforce winds can damage buildings and service facilities. The most severe
      damage from this occurs only when a typhoon strikes Shanghai directly. Second,
      both the urban and rural sections of Shanghai are liable to flooding during
      typhoon seasons. These floods occur when typhoon-induced storm surges coincide
      with high spring tides and meet with high discharges from the river network as a
      result of the typhoon downpours. Third, typhoon-induced torrential rain has
      caused waterlog hazards, particularly in the most densely populated parts of
      Shanghai. The waterlog hazard has been exacerbated by land subsidence and poor
      management of pumping systems. In order to prevent disasters happening and reduce
      the scale of damage, the government has issued construction guidelines and
      invested in flood defences. Further measures are to be brought in including
      engineering projects, educational programmes and insurance policies.

PMID- 10204289
TI  - [The formation of a set based on illusory representations and during the
      perception of concrete visual stimuli].

PMID- 10204291
TI  - [Electrophysiological studies of human spatial vision under interference
      conditions].

PMID- 10204290
TI  - [The regional and hemispheric specialization of the operations of visual
      recognition. The age-related aspect].

PMID- 10204292
TI  - [The manifestation in human long-latency auditory evoked potentials of the
      phenomenon of successive backward masking].

PMID- 10204293
TI  - [The participation of the left and right hemispheres of the human brain in the
      formation of a subjective acoustic space].

PMID- 10204294
TI  - [Speech as an index of the states of persons in operator jobs and of depressed
      patients].

PMID- 10204295
TI  - [The origin of subjective experiences as a problem in human brain physiology].

PMID- 10204296
TI  - [The periodic mobility of the cranial bones in man].

PMID- 10204297
TI  - [Brain proteinase activity and the mobilization of endogenous proteolytic
      inhibitors as factors in the development of the functional state of the body].

PMID- 10204298
TI  - [The possibilities of Holter ECG monitoring in studying the rhythm of cardiac
      activity in pediatrics].

PMID- 10204299
TI  - [Muscular reception and a generalized description of body posture].

PMID- 10204300
TI  - ["Biological reliability", ontogeny and the age-related dynamics of muscular work
      capacity].

PMID- 10204301
TI  - [The thermal imaging assessment of peripheral vascular reactions during local
      cold exposure in subjects with differing hypoxic resistances].

PMID- 10204302
TI  - [The neurophysiological mechanisms in the selection of actions and their
      disturbance in the attention deficit syndrome].

PMID- 10204303
TI  - [The problem of the segmental description of the human electroencephalogram].

PMID- 10204304
TI  - [Autoinduced myocardial tolerance to ischemia: the role of stress proteins in the
      mechanisms of its occurrence].

PMID- 10204305
TI  - [The effect of food additives containing polyunsaturated fatty acids on
      intraerythrocyte metabolism and hemoglobin oxygen affinity in volleyball players
      during exposure to intensive physical loading].

PMID- 10204306
TI  - [De novo neoplasms in transplant patients].
AB  - To identify the number of patients with de novo tumors in organ transplant
      recipients, we collected the information from eleven hospitals of the Instituto
      Mexicano del Seguro Social with organ transplant programs. During a period of 9
      years, we found only five cases of neoplasia. The median age was 26 years. All
      tumor occurred in renal transplant recipients. All patients received
      cyclosporine, azathioprine and steroids. One breast tumor, one renal carcinoma,
      two Kaposi's sarcoma and one angioleiomyosarcoma were found. The frequency of
      tumors in these patients is lower than reported by other authors, probably due,
      in our series to the fact that the patients were younger and the existence of a
      recently created transplant program with a short period of follow-up.

PMID- 10204308
TI  - [The clinical phenomenology of Rett's syndrome].
AB  - The work was done to facilitate the clinical diagnosis and understanding of Rett
      syndrome (RS) by grouping the symptoms and signs in areas of neurological
      disfunction. This is a retrospective, longitudinal and observational study of 30
      young females whose clinical manifestations were grouped using a modified
      Fitzgerald et al. scale for motor and behavior evaluation of patients with RS.
      All patients were videotaped at least during one or several appointments during
      their follow-up for a period of 1 to 10 years. All patients and videotapes were
      reviewed independently by the three authors. We followed the clinical diagnostic
      criteria of classic RS, and grouped the symptoms and signs in 12 groups of
      clinical phenomenology that represented specific areas of central or peripheral
      nervous system involvement: 1) dementia syndrome (fronto-temporo-parietal and
      limbic dysfunction); 2) extrapyramidal syndrome (basal ganglia dysfunction); 3)
      respiratory function disorders (brain stem reticular system disfunction); 4)
      sleep disorders (reticular system and limbic dysfunction); 5) epilepsy (cortico
      subcortical paroxysmal bioelectrical dysfunction); 6) lower motor neuron syndrome
      (neuropathic dysfunction and/or peripheral neuropathy); 7) body growth
      retardation; 8) tonic-postural skeletal deformities; 9) deficit of pain sensation
      (nociceptive deficit); 10) pseudobulbar dysfunction; 11) autonomic dysfunction
      and 12) others (microcephaly and bruxism). In clinical practice, we recommend the
      use of this grouping of symptoms and signs because it makes facilities the
      clinical study, definition of areas of dysfunction and diagnosis of the patient
      with RS.

PMID- 10204307
TI  - [Hypertriglyceridemia during active intercurrent infections in HIV-infected
      patients].
AB  - BACKGROUND: Many reports have confirmed that hypertriglyceridemia (HTG) is more
      common in HIV-infected patients than in the general population, but the
      relationship between HTG and clinical conditions have not been well established.
      This work analyzes the relationships between CD4+ cell count, HTG and the
      presence of active intercurrent infections in patients hospitalized for HIV
      infection. METHODS: Blood specimens from hospitalized HIV-infected patients and
      healthy controls without HIV infection were analyzed. Clinical conditions when
      the specimens were collected were recorded. RESULTS: The average level of serum
      triglycerides from 89 HIV-infected patients was significantly higher than the 29
      healthy controls (1.57 +/- 0.09 vs 0.78 +/- 0.08 mmol/l respectively) (p <
      0.001). In the study group, HTG was detected in 25 patients (27%). Twenty-six
      patients had intercurrent infections and 50 were asymptomatic. Clinical
      conditions of the remaining 13 were not available. HTG was detected in 18 out of
      26 patients having intercurrent infections (68%), and in 4 out of the 50 patients
      without active infections (8%) (p < 0.000000417). CONCLUSIONS: HTG was more
      frequent in HIV-infected patients than in healthy controls, and it was
      significantly associated with the presence of intercurrent infections. This has
      important diagnostic implications, because the presence of HTG might be
      considered an unspecific marker for intercurrent infections in HIV patients.

PMID- 10204309
TI  - [The domestic inhalation of the smoke from firewood and of other biological
      materials. A risk for the development of respiratory diseases].
AB  - A high proportion of the world population, especially in developing countries, is
      exposed to indoor pollutants produced by inefficient biomass stoves. The levels
      of pollutants, including toxins and carcinogens in the kitchen are usually very
      high. This potential pathogenic exposure has been scarcely studied. The exposure
      to biomass smoke has been associated to chronic bronchitis and chronic airflow
      obstruction in adults and to acute respiratory infections in children. At the
      National Institute of Pulmonary Diseases in Mexico, we have observed the entire
      spectrum of diseases associated with tobacco in people who never smoked and who
      were exposed to wood smoke. Women exposed to wood smoke had a five-fold risk of
      chronic bronchitis and chronic airflow obstruction, as compared to the non
      exposed, according to a recent case-control study done at our Institute. The
      indoor levels of suspended particles smaller than 10 microns were frequently
      above 1,000 micrograms/m3 in a rural community in the state of Mexico. This
      information supports a causal role for biomass smoke for the genesis of several
      respiratory diseases, representing a potentially public health problem.

PMID- 10204310
TI  - [The prognostic importance of the measurement of DNA in solid tumors].

PMID- 10204311
TI  - [Medical pathology due to trinucleotide repeats].
AB  - Trinucleotide repeat expansion is responsible for ten human diseases described so
      far. Four types of repeats are involved in these expansions, with type, number
      and position in the gene varying from one disease to another. In some fragile
      sites, the trinucleotide repeat is found to be enlarged to 200 or more. Smaller
      expansions have been found within coding regions of some genes that are
      associated with neurodegenerative diseases, such as Huntington's disease. The
      continuous expansion of the trinucleotide repeats in subsequent generations
      explains the genetic anticipation, peculiar to these disorders. Recently, it was
      shown that two expanded minisatellite sequences are also involved in both
      progressive myoclonus epilepsy type 1 and distamycin A-sensitive fragile site,
      FRA16B. This form of peculiar heredity is very important because of its
      relationship with some of the common human degenerative diseases.

PMID- 10204312
TI  - [By way of a synthesis of its conceptual evolution towards scientific medicine].
AB  - A historic outline of the evolution of medical thought toward scientific medicine
      is presented. Galen from Pergamon, one of science's first philosophers, wrote an
      Institutio logica, which can be considered as an introduction to the scientific
      method. Later, the Nominalists of the XIV century, precursors of modern science,
      thought that science's object was not the general, vague and indeterminate, but
      the particular, which is real and can be known directly. About the middle of the
      XVII Century the bases of the modern science became established thanks to a
      revolution formented essentially by Galileo, Bacon and Descartes. During the
      XVIII Century, parallel to the development of the great current of English
      Empiricism, a movement of scientific renewal also arose in continental Europe
      following the discipline of the Dutch Physicians and of Boerhaave. In the last
      century, Claude Bernard dominated scientific medicine, but his rigorous
      determinism impeded him from taking into account the immense and unforeseeable
      field of the random. Nowadays, we approach natural science and medicine from
      particular groups of facts, that is, from the responses of Nature to specific
      questions, but not from general laws. Furthermore, in recent epistemology, the
      concept that experimental data are not pure facts, but rather, facts interpreted
      within a hermeneutical context has been established. Finally, a general tendency
      to retrieve philosophical questions concerning the understanding of essence and
      existence can frequently be seen in scientific inquiry. In the light of the
      evolution of medical thought, it is possible to establish the position of
      scientific medicine within the movement of ideas dominating in our time.

PMID- 10204313
TI  - [The origin and development of hospital residencies].

PMID- 10204314
TI  - [The first nurses on the American continent].

PMID- 10204315
TI  - [Acute methyl parathion poisoning with extrapyramidal manifestations not
      previously reported].
AB  - A 14-year-old female attempted suicide by ingesting the organophosphate methyl
      parathion. A severe acute poisoning developed with the characteristic
      symptomatology: muscarinic, nicotinic and neurologic, as well serum
      cholinesterase activity decreased 88%. An extrapyramidal syndrome appeared
      suddenly nine days after the onset with ocular and buccal crisis, neck and trunk
      dystonic movements, and hypertonia and tremors. The patient improved with the
      administration of i.v. diphenhydramine. Other causes of toxic extrapyramidalism
      and organophosphate intermediate syndrome were discarded. Although an absolute
      causal relationship of the transient extrapyramidal symptomatology to the
      organophosphate exposure cannot be clearly established in this case, we speculate
      a possible delayed inhibition of the dopaminergic receptors in the substantia
      nigra and the basal ganglia.

PMID- 10204316
TI  - [A fibrolamellar variety of hepatocarcinoma in a young woman 17 years old].
AB  - We report here the case of a 17-year-old female with typical fibrolamellar
      hepatocellular carcinoma, no hepatitis B or C viral infection and a normal, non
      cirrhotic liver. Computed tomography and magnetic resonance imaging revealed a
      solid tumor with a central fibrous scar. A fibrolamellar hepatocellular carcinoma
      is an uncommon malignancy of unknown etiology, without cirrhosis, usually without
      an increase in tumor markers, and rarely associated with hepatitis B virus. It
      occurs mainly in young patients. This tumor presents a high resectability rate
      (48-100%), a good prognosis and a mean survival of 68 months. This tumor is an
      important differential diagnosis of space occupying lesions in younger adults.

PMID- 10204317
TI  - [The genes of bone tumor susceptibility].

PMID- 10204318
TI  - [New drugs in the treatment of type-2 diabetes mellitus].

PMID- 10204319
TI  - [The National Medical Arbitration Commission].

PMID- 10204320
TI  - [Diaphragmatic eventration].

PMID- 10204321
TI  - [Medical and surgical books printed in New Spain ...].

PMID- 10204322
TI  - Investigating rating scale category utility.
AB  - Eight guidelines are suggested to aid the analyst in investigating whether rating
      scales categories are cooperating to produce observations on which valid
      measurement can be based. These guidelines are presented within the context of
      Rasch analysis. They address features of rating-scale-based data such as category
      frequency, ordering, rating-to-measure inferential coherence, and the quality of
      the scale from measurement and statistical perspectives. The manner in which the
      guidelines prompt recategorization or reconceptualization of the rating scale is
      indicated. Utilization of the guidelines is illustrated through their application
      to two published data sets.

PMID- 10204323
TI  - Using IRT variable maps to enrich understanding of rehabilitation data.
AB  - One of the benefits of item response theory (IRT) applications in scale
      development is the greater transparency of resulting scores. This feature allows
      translation of a total score on a particular scale into a profile of probable
      item responses with relative ease, for example by using the variable map that
      often is part of IRT analysis output. Although there have been a few examples in
      the literature using variable maps to enrich clinical interpretation of
      individual functional assessment scores, this feature of IRT output has received
      very limited application in rehabilitation research. The present paper
      illustrates the application of variable maps to support more in-depth
      interpretation of functional assessment scores in research and clinical contexts.
      Two examples are presented from an outcome prediction study conducted during the
      standardization of a new functional assessment for elementary school students
      with disabilities, the School Function Assessment. Two different applications are
      described: creating a dichotomous outcome variable using scores from a continuous
      scale, and interpreting the meaning of a classification cut-off score identified
      through Classification and Regression Tree (CART) analysis.

PMID- 10204324
TI  - Measuring pretest-posttest change with a Rasch Rating Scale Model.
AB  - When measures are taken on the same individual over time, it is difficult to
      determine whether observed differences are the result of changes in the person or
      changes in other facets of the measurement situation (e.g., interpretation of
      items or use of rating scale). This paper describes a method for disentangling
      changes in persons from changes in the interpretation of Likert-type
      questionnaire items and the use of rating scales (Wright, 1996a). The procedure
      relies on anchoring strategies to create a common frame of reference for
      interpreting measures that are taken at different times and provides a detailed
      illustration of how to implement these procedures using FACETS.

PMID- 10204326
TI  - Parameter recovery for the rating scale model using PARSCALE.
AB  - The purpose of the present study was to investigate item and trait parameter
      recovery for Andrich's rating scale model using the PARSCALE computer program.
      The four factors upon which the simulated data matrices varied were (a) the
      distribution of the scale values for the items (skewed or uniform), (b) the
      number of category response options (4 or 5), (c) the distribution of known trait
      levels (normal or skewed), and (d) the sample size (60, 125, 250, 500, or 1,000).
      Each condition was replicated 10 times resulting in 400 data matrices. Accurate
      item and trait parameter estimates were obtained for all sample sizes examined.
      As expected, sample size seemed to have little influence on the recovery of trait
      parameters but did influence item parameter recovery. The distribution of known
      trait levels did not seriously impact the item parameter recovery. It was
      concluded that Andrich's rating scale model allows for the use of considerably
      smaller calibration samples than are typically recommended for other polytomous
      IRT models.

PMID- 10204325
TI  - Grades of severity and the validation of an atopic dermatitis assessment measure
      (ADAM).
AB  - There has generally been a dearth of good clinical descriptions of grades of
      disease severity. The aim of this study was to produce reliable and valid
      descriptions of grades of severity of Atopic Dermatitis (AD). The ADAM (AD
      Assessment Measure) measure was used to assess AD severity in 171 male and female
      paediatric patients (mean age = 54 months) at the Royal Children's Hospital in
      Melbourne, Australia. The assessments were subject to Partial Credit analyses to
      produce clinically relevant "word pictures" of grades of severity of AD. Patterns
      of AD were shown to vary according to age, sex and severity. These descriptions
      will be useful for clinical training and research. Moreover, the approach to
      validation adopted here has important implications for the future of measurement
      in medicine.

PMID- 10204327
TI  - Special issue: racial issues in health care.

PMID- 10204329
TI  - Community oriented primary care: an ethical analysis.

PMID- 10204328
TI  - Racial disparities in health: a sociological analysis.

PMID- 10204330
TI  - The practice of community oriented primary care: an ethical appraisal.

PMID- 10204331
TI  - Transplantation, the organ gap, and race.

PMID- 10204332
TI  - Race and health care.

PMID- 10204333
TI  - The Placemat Strength Training Program.

PMID- 10204334
TI  - Maude Evelyn Callen, RN (1898-1990).

PMID- 10204335
TI  - [The drug correction of functional disorders of blood coagulation and lipid
      peroxidation in patients with infectious myocarditis].
AB  - Carried out in this study for the first time was the diagnosis and treatment per
      groups of degree of severity of the clinical course of infectious myocarditis.
      According to the classification of the New York Association of Cardiology (1964,
      1973), there has been established a clear correlation between the gravity of the
      process course, hemodialysis and cardiac haemodynamics.

PMID- 10204336
TI  - [The morphofunctional changes in the erythrocytes in cerebral vascular lesions in
      patients with hypertension and cerebral arteriosclerosis].

PMID- 10204338
TI  - [The pharmacological characteristics and clinical use of low-molecular-weight
      heparins].

PMID- 10204337
TI  - [The morphology, microbiology and ultrasonic diagnosis of calculous
      cholecystitis].

PMID- 10204339
TI  - [Pro- and antiatherogenic mechanisms in chronic kidney failure].
AB  - Atherosclerosis is a very common complication and frequently recordable cause of
      death in patients with chronic renal insufficiency (ChRI). The authors focus on
      current notions about causes of rapidly advancing atherosclerosis in patients
      presenting with manifest and terminal ChRI, who were exposed to a conservative
      treatment, programme hemodialysis or prolonged peritoneal dialysis. Treated in
      the article at length are proatherogenic (generally known, common in ChRI only)
      and antiatherogenic mechanisms. A worthwhile line of investigations is suggested
      to be designed to study ChRI pathogenesis and devise relevant preventive and
      curative measures.

PMID- 10204340
TI  - [X-ray computed tomography in the diagnosis of perinatal cerebrovascular lesions
      in infants].

PMID- 10204341
TI  - [The assessment of the status of the cardiovascular system in people who were
      victims as a result of the accident at the Chernobyl Atomic Electric Power
      Station (based on ultrasonic diagnostic data)].
AB  - A lack of compliance has been disclosed of left ventricular parameters and those
      parameters characterizing myocardial contractility with age-scale norms in a
      major proportion of cases in a series of 229 patients presenting with different
      abnormalities of the internals who had become victims of the Chernobyl accident,
      as per echocardiographic examination. By comparison with other groups of
      nosological entities the most pronounced changes were seen in those patients
      presenting with cardiovascular disorders, their degree being dependent upon the
      functional class in ischemic heart disease and stage of hypertensive disease. The
      ejection fraction approaching the norm under changed volumes of left ventricular
      cavity suggests some bodily compensatory potential.

PMID- 10204342
TI  - [The dynamics of the autonomic indices in participants in the cleanup of the
      aftermath of the accident at the Chernobyl Atomic Electric Power Station at the
      stages of therapeutic hyperoxia].
AB  - Time-related course was studied of vegetative indicators during the hyperbaric
      oxygenation (HBO) sessions in 36 liquidators of the effects of the Chernobyl
      Nuclear Power Plant breakdown, who suffered from early forms of cerebrovascular
      insufficiency. Shown for the first time in therapeutic hyperoxia in the
      liquidators are features of the time-related course of vegetative regulation.
      Significant group particularities of changes in vegetative regulation have been
      stated, that suggest a different approach to the tactics of HBO employment. Those
      patients experiencing a higher tenseness of vegetative regulation demonstrated
      antecedents of toxic action of oxygen at minute 35 to 40 HBO. The employed
      vegetative indicators monitoring technology allowed the establishment of
      individualized hyperoxia doses, with the early signs of oxygen overdose being
      revealed in real time.

PMID- 10204343
TI  - [The characteristics of the clinical picture and of the psychotherapy of
      somatogenically induced neurosis-like disorders in people subjected to ionizing
      radiation exposure as a result of the accident at the Chernobyl Atomic Electric
      Power Station].
AB  - In a 10-year follow-up the time-related course was studied of neurosis-like
      disorders in those subjects presenting with digestive abnormalities. The group of
      examinees was 108 patients--liquidators of the Chernobyl accident who had come to
      be exposed to the doses of irradiation of the order of 0.7 Gy and higher, persons
      who had suffered acute radiation sickness. Rise in morbidity is shown. Some
      principles are suggested of devising rehabilitation measures together with
      therapeutic ones aimed to correct somatic disorders presenting with concurrent
      psychoneuronal type problems.

PMID- 10204344
TI  - [An epidemiological analysis of the health status of the participants in the
      cleanup of the aftermath of the accident at the Chernobyl Atomic Electric Power
      Station].
AB  - A comparative analysis has been carried out of indices for health status in
      137,072 persons who took part in the elimination of the aftermath of the
      Chernobyl accident, using records of the National Register of Ukraine. The above
      mentioned indices were for time-related general morbidity, mortality, disability
      during the period of 1988-1996. There has been revealed yearly increase in
      morbidity rates in all classes of diseases, in particular those of the
      circulatory system, nervous system, and sense organs, digestive, and respiratory
      systems. High morbidity rates are recordable with respect to that class of
      diseases afflicting the endocrine system, blood, and hemopoietic organs,
      neoplasms including malignant tumours. The disability rates tended to increase
      above average statistical ones for Ukraine.

PMID- 10204345
TI  - [Genetic monitoring of the population of the Carpathian region under
      anthropogenic pollution of the environment].
AB  - A genetic monitoring was conducted in a number of ecological regions of
      Precarpathia on the basis of clinical and epidemiological indices for the
      frequency of spontaneous abortions, specific weight of multiple birth, dynamics
      of number born living over the twelve-year period of 1985-1996, with the
      incidence and nosological spectrum of congenital malformations and hereditary
      diseases having been characterized. Negative genetic changes were disclosed in
      those communities under health-hazard conditions. Predominance of spontaneous
      abortions early in gestation was established together with decline in birth rate,
      increase in perinatal mortality, congenital malformations, and hereditary
      diseases in neonates and in children having died in the perinatal period.

PMID- 10204346
TI  - [Lipid peroxidation and the antioxidant system in subjects exposed to the
      influence of extreme factors].
AB  - Data are submitted from the published literature and the authors' investigations
      on the state of lipid peroxidation (LPO) and antioxidant defence (AOD) in
      liquidators of the effects of the Chernobyl accident and those working under
      watch rate. Both groups patients revealed activation of LPO and AOD processes.
      Long-continued activation of AOD can lead to its exhaustion and become a trigger
      factor in the development of cardiovascular diseases and digestive disorders.

PMID- 10204347
TI  - [The characteristics of the course of chronic dust-induced bronchitis in workers
      in granite quarries].
AB  - Our objective in this study was to go into particular features of the clinical
      course that chronic bronchitis runs in those men working in granite quarries. The
      studies made showed chronic bronchitis to have peculiar clinical manifestations
      leading to the development of pulmonary insufficiency and diffuse pneumosclerosis
      presenting with atrophic and sclerosal changes in bronchial mucosa.
      Investigations designed to study systemic immunity status permitted the changes
      in the T-system to be revealed, with indices for the B-system being in the normal
      range.

PMID- 10204348
TI  - [The health-promoting effect of physical exercises in the work of schoolchildren
      at computers].
AB  - The results of the studies made showed that work at a computer leads to high
      strain of visual analyzer and of central nervous system. Physical exercises are
      supposed to be performed during those classes involving the use of a computer by
      schoolchildren. We have developed such a complex of exercises in the form of
      "phizkulminutka" (a series of physical exercises one minute in total duration).

PMID- 10204349
TI  - [The characteristics of the realization of myocardial ischemia as dependent on
      stress test results in women with myocardial lesions of various origins].
AB  - Overall, 72 female subjects presenting with chest pain and/or ST changes in ECG
      were studied. Average age of the examinees was 44.6 years, all the above women
      being less than 67 years old. Certain differences were found in those subjects
      presenting with non-Q-wave myocardial infarction, unstable angina, function
      disorders of the cardiovascular system, as per transesophageal
      electrocardiostimulation. Stress-tests results were studied for an objective
      appraisal to be done of the myocardium function state.

PMID- 10204350
TI  - [Left ventricular function in pulmonary arterial hypertension].
AB  - Echocardiographic evaluation was done of left ventricular functional state in 90
      patients with primary and secondary pulmonary arterial hypertension with and
      without intercavitary shunting. Changes in left ventricular function were
      identified in 86% cases; they reflected disturbances in both ventricles
      compensatory interaction. The degree of changes depended on the degree of
      dilatation of the right ventricle and level of interchamber shunting.

PMID- 10204351
TI  - [The characteristics of the morphofunctional restructuring of the aortic
      endothelium in food-related atherosclerosis and hyperadrenalinemia].
AB  - Morphofunctional reorganization was studied of endothelium during the stage of
      formation of alimentary atherosclerosis and in experimental hyperadrenalinemia
      using transmission electronic microscopy and histochemistry together with silver
      nitrate impregnation of aortal endothelial monolayer. Certain morphofunctional
      equivalents have been established for the vascular wall exposure to the above
      factors, indicative of their unequalability and possibility of potentiation under
      combination. In both cases, an interrelationship similar in character has been
      shown between intensity of the endothelial reciprocal response and its regional
      morphofunctional features.

PMID- 10204352
TI  - [The sorption kinetics in an immunosorbent of circulating immune reactants in the
      blood of patients with systemic lupus erythematosus].
AB  - In a double-blind trial blood content was studied of antibodies to nDNA and dDNA
      (AB-nDNA and AB-dDNA) using methods of solid-phase and liquid-phase immunoassay,
      of circulating immune complexes (CIC), beta 2-microglobulin (beta 2-MG), Ig G, M,
      and A during the time-related run of two sessions of immunosorption (IS) or
      nonselective hemosorption (NHS) in 22 patients with systemic lupus erythematosus.
      In eleven patients there was employed for IS DNA-containing active carbon, in
      other eleven patients carbon was used for NHS. Throughout the whole IS session
      high- and low-avid AB-nDNA and CIC were getting fixed with the sorbent followed
      by AB-dDNA, with the concentration gradient for these substances in the column
      being greater at minute 30 than it was at minute 15. The control carbon fixed AB
      nDNA and AB-dDNA as measured by ELISA but at the start of the session it did so
      also with low-avid AB-at minute 30. At minute 15 of perfusion the blood level of
      low-avid AB-nDNA and AB-dDNA following the column procedure tended to
      significantly increase both in NHS and, to a lesser extent, in IS. Neither of the
      sorbents adsorbed IG. Decline in beta 2-MG concentration in columns with
      engrafted and matrix carbon at the start of the perfusion and its rise during the
      second half of the session might be caused by blood cells structural and
      functional condition as a result of their interaction with the sorbent in
      question.

PMID- 10204353
TI  - [The mineral density of the bone tissue in patients with rheumatic diseases of
      the joints (based on x-ray densitometry data)].
AB  - Manifestations were studied of systemic osteoporosis in patients with rheumatoid
      arthritis, primary osteoarthrosis, and ankylosing spondylarthritis. There have
      been disclosed differently directed changes in mineral density of lumbar spine
      and thigh bone segments related to phase of the illness as well as to the
      treatments administered, patient age, and impact of the post-menopausal period
      (in female patients). A conclusion has been reached that it is necessary that the
      above-mentioned studies be made in order that we might choose relevant
      therapeutic alternatives for patients with rheumatic afflictions of the joints.

PMID- 10204355
TI  - [The interrelationship of gallbladder contractile function, the morphological
      status of the mucosa of the gastroduodenal area and its Helicobactor pylori
      colonization in patients with duodenal peptic ulcer].
AB  - Studied in 130 patients with duodenal ulcer were contractility of the
      gallbladder, morphological state of mucosa of the gastrointestinal zone,
      infection of the above-named mucosa with Helicobacter pylori, and ultrastructure
      of I-cells. Function disorders of the gallbladder were found out to be directly
      proportional to the degree of injury to the gastroduodenal zone mucosa and to the
      extents of H. pylori growth. There has been established correlation between
      disturbances in the intracellular architectonics of L-cells and state of motility
      of the gallbladder.

PMID- 10204356
TI  - [Liver function and the level of total cholesterol in the blood serum in liver
      cirrhosis].
AB  - The authors have analyzed findings from a laboratory examination of 50 subjects
      presenting with different affections of the liver. Correlation is established
      between the level of total cholesterol and activity of alanine aminotransferase
      in blood serum of cirrhotic patients, it being particularly clear in portal
      cirrhosis (r = -0.85; P < 0.05), as well as significantly higher levels of total
      and indirect bilirubin and lower level of albumins in patients presenting with a
      reduced level of total cholesterol. This allows the decrease in the blood serum
      content of total cholesterol to be regarded as an unfavourable index in
      hepatocirrhosis.

PMID- 10204357
TI  - [The effect of acute and chronic overheating on morphological changes in the
      liver].
AB  - Disturbances were disclosed in the functioning of the lysosomal and vacuolar
      apparatus in an electronic and histochemical investigation of 75 Wistar albino
      rats and 10 control animals exposed to acute and chronic overheating, with the
      numbers and structure of lysosomes undergoing changes, lysosomal membranes
      disrupting, which event was accompanied by an outgo of lysosomal contents into
      the cellular cytoplasm and beyond. There was no longer Golgi apparatus as a
      single whole; cellular cytoplasm stored lipid drops of low electron density with
      membrane inclusion and products of reaction to acid phosphatase in their matrix.
      Disruption of lysosomes and identification of acid phosphatase in cellular
      cytoplasm and Disse's space was presumably a cause of damage to the Golgi
      apparatus.

PMID- 10204359
TI  - [An amino acid metabolic complex in optimizing the cardiac hemodynamic
      characteristics of patients with ischemic heart disease].
AB  - On the basis of findings from examination of 82 patients with ischemic heart
      disease presenting with exertional angina, functional class II-III, aged 62-86
      years, efficacy was studied of an amino acid metabolic complex consisting of
      glutamic acid and methionine combined with basic antianginal drugs and single
      basic therapy with nitrates and calcium antagonists. Criteria for efficacy were
      condition of central cardiohemodynamics and inotropic indices. Glutamic acid and
      methionine combined with basic agents were found to make for enhancement of
      contractile function of ischemized myocardium, with the left ventricular local
      contractility being improved against the background of reduction in postload.

PMID- 10204358
TI  - [The efficacy of active specific immunotherapy using modified neoplastic cells in
      the combined modality treatment of hemoblastoses].
AB  - Efficiency was studied of active specific immunotherapy (IT) with cell vaccine
      consisting of allogenic viable cryopreserved modified Con A blast cells identical
      with the illness in patients with acute myeloblastic leukemia and acute
      lymphoblastic leukemia. The studies made confirmed a positive impact of IT on the
      clinical course of acute leukosis (prolonged remission, keeping down infectious
      complications), on leukopoiesis, peripheral blood cells enzymatic status as well
      as on cell immunity, certain factors of humoral immunity and bodily natural
      antineoplastic resistance.

PMID- 10204361
TI  - [The pathogenesis of cardiovascular system lesions in patients with chronic
      acalculous cholecystitis].
AB  - As many as 42 patients with chronic noncalculous cholecystitis who ranged from 18
      to 36 years old were studied for the left ventricular systolic-and-diastolic
      function and for humoral immunity. Signs of left ventricular diastolic
      dysfunction were revealed as were increased levels of complement-fixing
      antibodies to the tissues of the gallbladder and myocardium. It is suggested that
      one of the pathogenetic mechanisms of the abnormal changes in the cardiac muscle
      might be immune factors for there is a similarity between antigenic determinants
      of the gallbladder and myocardium tissues antigen.

PMID- 10204360
TI  - [The effect of diltiazem on the systemic hemodynamics of patients with heart
      failure due to ischemic heart disease].
AB  - Dilthiazem has been shown to exert a positive effect on haemodynamics in patients
      in different stages of heart failure. Reduction in postload under the influence
      of dilthiazem is a cardinal factor of improvement of intracardiac haemodynamics
      making for increase in cardiac output and regional blood flow.

PMID- 10204362
TI  - [The current methods for treating chronic calculous cholecystitis and reactive
      hepatitis].
AB  - In conducting pathogenetic treatment of chronic calculous cholecystitis it is
      necessary that special characteristics of development of the clinical course in
      the above condition be studied together with phase contractile function of the
      gallbladder, liver, as per duodenum motility phases. The above methodological
      approach to the treatment of chronic calculous cholecystitis, reactive hepatitis
      will, we believe, come to be widely used by medical practitioners.

PMID- 10204363
TI  - [Fibrous-cavernous pulmonary tuberculosis in diabetics].
AB  - A total of 75 patients with diabetes mellitus who underwent surgical
      interventions on the lungs for fibrocavernous tuberculosis were followed up. A
      complex preparation for surgery being completed, operative interventions under
      endotracheal narcosis were carried out in all cases. Postoperative complications
      occurred in 32 percent of cases, four patients (5.33%) died after the operation.
      The clinical efficiency was recordable in 94.87 percent of patients. During the
      postoperative 1- to 15-year follow-up the achieved effect was still to be seen in
      83.8 percent of those having been operated on. A major proportion of patients
      showed improvement in the course of diabetes mellitus.

PMID- 10204364
TI  - [The pathogenetic mechanisms of bronchospasm in different clinical forms of
      chronic bronchitis].
AB  - The article is dedicated to the study of main links of pathogenesis of
      bronchospasm of chronic obstructive bronchitis, establishing differential and
      diagnostic criteria of obstructive and asthmatic bronchitis to find new
      approaches toward treatment of bronchospasm. A comparison has been made between
      clinical and laboratory findings that can be helpful in quests for an efficient
      treatment option of the above condition.

PMID- 10204365
TI  - [The prognosis of postoperative bronchopulmonary complications in the surgical
      treatment of inflammatory diseases of the hepatobiliary system].
AB  - Operations for inflammatory diseases of the hepatobiliary system are accompanied
      in 16 percent of cases by development of pneumonias in the postsurgical period.
      In statistical treatment of the material, the principal risk factors for
      development of pneumonia were established as was their prognostic significance.
      The use of diagnostic coefficients allows the most important prognostic criteria
      to be assessed in a complex manner, the integral value for the index of risk for
      development of postsurgical pneumonia to be computed. Depending on magnitude of
      the index, patients are divided into three groups of risk for development of
      complications, with the prophylaxis being directed to differentiated use of
      complexes of measures for each of the groups.

PMID- 10204366
TI  - [The acid-base status of preserved blood before and after processing with an
      oxygen-ozone mixture].
AB  - Effects were studied of oxygen and ozone mixture on the indices for the contained
      donor blood acid-base state. Ozonation of blood in 9 donors was carried out in
      different concentrations of ozone in the oxygen and ozone mixture. Revealed in
      blood after ozonation was increase in oxygen concentration and decrease in CO2
      dissoluble fraction, with pH of blood, the content of bicarbonate being
      unchanged. There was no relatedness of the ozonized blood saturation with oxygen
      to the concentration of ozone in the oxygen and ozone mixture.

PMID- 10204367
TI  - [Hemopoietic cells from human embryonic liver in the treatment of HIV/AIDS].
AB  - Transplantation of human fetal liver cells is used for the deficient cellular
      mediators and humoral immunological factors to be efficiently replenished through
      proliferation and differentiation of embryonic stem cells contained in cellular
      suspensions. Kept under hospital observation were 17 patients: two female
      patients aged 24 and 40 years respectively and 15 male patients with a mean age
      of 35 years. There were no instances of intolerance, side effects, graft-versus
      host reaction. Informed consent was elicited from the patients to performing
      grafting.

PMID- 10204369
TI  - [The recovery of atypical mycobacteria from patients with urogenital diseases].
AB  - In 76 patients with genitourinary disorders an identification was carried out of
      atypical mycobacteria from the pathological material with subsequent
      categorization thereof into different groups according to Rennieun's
      classification. There have been established different numbers of recovering
      atypical mycobacteria, tuberculosis mycobacteria and their myxts in different
      urological and genital disorders, such as tuberculosis and cyst of the kidney,
      tuberculosis of appendages, chronic pyelonephritis, adenoma of the prostate. The
      conducted studies showed that the bulk of atypical mycobacteria identified in the
      above-named patients belonged in group II (scotochromogenes) and IV (fast
      growing) as per Rennieun's classification.

PMID- 10204368
TI  - [The use of the alpha 1-adrenoblocker doxazosin in the pharmacotherapy of
      disorders of urine outflow of spastic origin].
AB  - Our objective in this study was summing up of results of clinical studies on
      effectiveness of a selective alpha-adrenoblocker doxazosine in the
      pharmacotherapy of reflex and spastic disorders of outflow of urine. Doxazosine
      ("Cardura", Pfizer Inc.) was prescribed per os once per day in the morning after
      meal in a dose of 2-4 mg. The drug can be used not only as a hypotensive agent
      but also in conservative treatment of patients with prostate hyperplasia. It was
      found to be very effective in attempts to bring the disordered outflow of urine
      back to normal in patients presenting with calculi in the lower third of ureters
      as well as those with prior prostata resection; in affections of and injuries to
      the brain and spinal cord.

PMID- 10204370
TI  - [The results of using different forms of a Ginkgo biloba extract (EGb 761) in the
      combined treatment of patients with circulatory encephalopathy].
AB  - Studies made in 208 patients with discirculatory encephalopathy using clinical
      and neuropsychological tests, apparatus (REG, ECG, EEG, Doppler sonography) and
      laboratory (coagulogramme) methods showed the prescription of drug preparations
      from ginkgo extract to be a worth-while exercise likely to benefit the patient
      during different stages of his/her affection. Positive time-related course was
      recordable of change in elastic and tonic characteristics of vessels, of
      bioelectric brain activity, emotional and behavioral, cognitive and mnestic
      features. The above-mentioned drugs will, we believe, help in developing new
      options for the outpatient, hospital, and rehabilitative stage of managing a
      patient. Potentiation of the positive action of ginkgo preparations showed up
      when being combined with a complex of components of the tricarboxylic acid cycle.

PMID- 10204371
TI  - [The current pathogenetic approach to the diagnosis of atrophic brain processes
      of traumatic origin and after endomicrosurgical interventions].
AB  - Results have been analyzed of examination of 35 male patients aged 18-15 years.
      Of these, 25 presented with sequelae of closed craniocerebral injury
      (vegetovascular disorders presenting with rare epileptiform fits), 10 subjects-
      after having had their hematomas removed by endomicrosurgical techniques. All
      patients underwent computerized tomography of the brain and ultrasonic
      dopplerography of brain vessels. Shown in the paper is a high informative value
      of the above-named techniques in studying pathogenesis of intracranial
      hypertension, judging about the condition of brain tissue, liquor-containing and
      venous systems of the brain.

PMID- 10204372
TI  - [Perinatal risk factors for the development of autonomic disorders in premature
      newborns].
AB  - Disturbances in the premature neonate vegetative nervous system are often
      manifested by specific symptomatology, they can complicate the course of the
      underlying disorder. A total of 126 premature neonates with respiratory distress
      syndrome of non-septic genesis and hypoxic-ischemic affection of the central
      nervous system were kept under observation. Disturbances in the vegetative
      nervous system in the neonates during the first days of their lives develop
      chiefly under the influence of such perinatal factors as the course of pregnancy,
      institution in the neonate primary resuscitation measures, scores on Apgar scale,
      Ballard gestational age, and severity of status of the child during its early
      neonatal period. In elaborating hypothetical regression models risk for
      vegetative disorders with all risk factors combined is Rr = 21.37 and is 15 times
      as high as that with no above-named conditions.

PMID- 10204373
TI  - [The treatment of multiple brain abscesses].
AB  - Results are submitted of surgical treatment of 64 patients with multiple
      abscesses of the brain. The greatest benefit appeared to be from a combined
      treatment option involving different combinations of operative intervention
      (puncture, drainage, and complete removal) and, against this background, adequate
      doses of antibacterial agents. Overall fifty three patients (82.8%) underwent
      surgical treatment. Of these, 39.6 percent had their abscesses removed.
      Aspiration + drainage (22.6% of cases), aspiration + removal (16.9%) came in the
      second and third place respectively. Total mortality was 42.1%, operative
      mortality 35.7%. The lowest mortality level (16.6%) appeared to be in the
      combination of abscess puncture + drainage + removal. In the second place there
      came to be removal (death rate 28.7%) followed by the combination of puncture +
      removal (death rate 33.3%). Late operative intervention carried out in the
      patients during the stage of decompensation together with inadequate method of
      treatment were by far the commonest causes of the recorded mortality rates.

PMID- 10204374
TI  - [The histological changes and pathogenesis of an infarct of a long bone in soft
      tissue trauma to an extremity with damage to the feeding artery].
AB  - Acute disturbances in diaphysial intraosseous circulation secondary to the major
      nutrient artery intersection are not fully compensated from the potential
      intraosseous collaterals early in their course, which fact leads to bone
      infarction, as evidenced by histological and angiomorphological investigations in
      the experiment in rats. Recovery of ischemic tissues occurs in different time
      periods, necrotized myelokaryocytes undergo lysis, the bone marrow ischemic
      necrosis focus gets revascularized, with the reduced blood supply foci being
      intact, immature hemocytes scanty; necrotized osseous tissue undergoes
      revascularization and revitalization during the course of long-continued
      reorganization.

PMID- 10204375
TI  - [The characteristics of the course of viral hepatitis C].
AB  - Time-related course and results of examination were studied in patients with
      viral hepatitis C, having gotten infected through blood. Based on the comparison
      of similar indicators in patients with viral hepatitis B particular features were
      revealed of the clinical course of viral hepatitis C. These are as follows: short
      in-duration prejaundice period, in other instances there is no prejaundice period
      at all, subfebrile states set in quite often; among other features are dyspepsia
      like events together with signs of a damage to pancreas. There has been noted a
      slow dynamics of the icteric period reversibility, with biochemical indicators
      showing the same tendency.

PMID- 10204376
TI  - [The clinical aspects of discrete plasmapheresis in treating multiple organ
      failure in patients with the icterohemorrhagic form of leptospirosis].
AB  - Discrete-mode plasmapheresis using medium doses of separated plasma provides a
      detoxicating effect by eliminating of toxins, products of catabolism,
      biologically active substance, stimulation of gastrointestinal functions and
      cardiovascular system. Clinical application of plasmapheresis in a combined
      treatment of leptospirosis icterohaemorrhagica under multiorgan failure offers a
      highly efficient therapeutic alternative in alleviating the condition.

PMID- 10204377
TI  - [The efficacy of Intetrix in the combined treatment of patients with
      shigelloses].
AB  - Efficacy was studied of Intetrix in the treatment of acute Sonnei's shigellosis
      and Flexner's shigellosis in 32 patients presenting with mild and moderately
      severe course of their illness. The Intretrix group patients fared better
      compared with controls who received furazolidon as an etiotropic drug, with the
      duration of intoxication symptoms getting shorter, abdominal pains and diarrhea
      subsiding. Intetrix tended to be associated with a lower incidence of
      unfavourable outcomes, both immediate and remote ones. The data obtained show
      expediency of treatment with Intetrix of patients with shigelloses running a mild
      or moderately severe course.

PMID- 10204378
TI  - [Experience in identifying some non-self-evident correlations in syphilis].
AB  - The article focuses on the Wassermann test results correlations in syphilis with
      varying diagnoses. Depending on the course of negativation of seroreactions there
      comes to be a certain prognostic criterion of torpidity of syphilis course, with
      relevant treatment procedures outlined for the patients.

PMID- 10204379
TI  - [The use of acupuncture reflex therapy in the combined treatment of
      osteoarthrosis patients].
AB  - As many as 40 patients with osteoarthrosis of the hip and knee joints were
      followed up. Of these, 20 subjects received non-steroidal anti-inflammatory drugs
      together with intraarticular administration of glucocorticosteroids and
      inhibitors of proteases. The other 20 patients were exposed, apart from the above
      measures, to acupuncture treatments. Indicators of articular pains and tenderness
      of joints in palpation got significantly lower by the end of the course of
      treatment in those patients having received, in addition to drugs, acupuncture
      treatments.

PMID- 10204381
TI  - [The terms and concepts for a standards base for an oncological service. II. The
      treatment of malignant neoplasms].

PMID- 10204380
TI  - [Adrenal cyst].
AB  - A case is described of adrenal cyst removed by surgical means. The above-named
      cyst might be related to a damage to the adrenal gland or congenital small cyst.
      Following the large cyst removal, the small one began to progressively enlarge.

PMID- 10204382
TI  - [Means for the economic utilization of the beds in a treatment hospital under
      market terms].

PMID- 10204383
TI  - [The structure of the medical service units of the Ukrainian Insurgent Army].

PMID- 10204384
TI  - [Asbestos and health problems (based on the materials from the International
      Conference on the Safe Use of Chrysotile Asbestos, Ivano-Frankivs'k, 1-5 June
      1998)].

PMID- 10204385
TI  - Variable effort fishing models in random environments.
AB  - We study the growth of populations in a random environment subjected to variable
      effort fishing policies. The models used are stochastic differential equations
      and the environmental fluctuations may either affect an intrinsic growth
      parameter or be of the additive noise type. Density-dependent natural growth and
      fishing policies are of very general form so that our results will be model
      independent. We obtain conditions on the fishing policies for non-extinction and
      for non-fixation at the carrying capacity that are very similar to the conditions
      obtained for the corresponding deterministic model. We also obtain conditions for
      the existence of stationary distributions (as well as expressions for such
      distributions) very similar to conditions for the existence of an equilibrium in
      the corresponding deterministic model. The results obtained provide minimal
      requirements for the choice of a wise density-dependent fishing policy.

PMID- 10204386
TI  - On the quasi-stationary distribution of the stochastic logistic epidemic.
AB  - An approximation is derived for the quasi-stationary distribution of the
      stochastic logistic epidemic in the intricate case where the transmission factor
      R0 lies in the transition region near the deterministic threshold value 1. An
      approximation for the expected time to extinction from quasi-stationarity in the
      same parameter region is also given.

PMID- 10204387
TI  - Stochastic and deterministic models for SIS epidemics among a population
      partitioned into households.
AB  - Models for the spread of an SIS epidemic among a population consisting of m
      households, each containing n individuals, are considered and their behaviour is
      analysed under the practically relevant situation when m is large and n small. A
      threshold parameter R* is determined. For the stochastic model it is shown that
      the epidemic has a non-zero probability of taking off if and only if R* > 1, and
      the extension to unequal household sizes is also considered. For the
      deterministic model, with households of size 2, it is shown that if R* < or = 1
      then the epidemic dies out, whilst if R* > 1 the epidemic settles down to an
      endemic equilibrium. The usual basic reproductive ratio R0 does not provide a
      good indicator for the behaviour of these household epidemic models unless the
      household size n is large.

PMID- 10204388
TI  - Some state space models of HIV pathogenesis under treatment by anti-viral drugs
      in HIV-infected individuals.
AB  - In this paper we have extended the model of HIV pathogenesis under treatment by
      anti-viral drugs given by Perelson et al. [A.S. Perelson et al., Science 271
      (1999) 1582] to a stochastic model. By using this stochastic model as the
      stochastic system model, we have developed a state space model for the HIV
      pathogenesis under treatment by anti-viral drugs. In this state space model, the
      observation model is a statistical model based on the observed numbers of RNA
      virus copies over different times. For this model we have developed procedures
      for estimating and predicting the numbers of infectious free HIV and non
      infectious free HIV as well as the numbers of different types of T cells through
      extended Kalman filter method. As an illustration, we have applied the method of
      this paper to the data of patient Nos. 104, 105 and 107 given by Perelson et al.
      [A.S. Perelson et al., Science 271 (1999) 1582] under treatment by Ritonavir. For
      these individuals, it is shown that within two weeks since treatment, most of the
      free HIV are non-infectious, indicating the usefulness of the treatment.
      Furthermore, the Kalman filter method revealed a much stronger effect of the
      treatment within the first 10 to 20 h than that predicted by the deterministic
      model.

PMID- 10204389
TI  - A new design of stochastic partnership models for epidemics of sexually
      transmitted diseases with stages.
AB  - A problem of importance in modelling epidemics of sexually transmitted diseases
      is the development of mathematical structures accommodating sexual and other
      contacts among members of a population. Because these models may be complex, it
      is often necessary to use computer intensive methods in their analysis, which
      raises questions on the design of computer models. In this paper a new approach
      to designing models sexual contacts is presented within the context of a
      stochastic model accommodating the formation and dissolution of partnerships in
      heterosexual populations. Emphasis will be placed on the development of
      algorithms with a view towards developing software to implement computer
      intensive methods. Unlike previous formulations, rather than using rejection
      methods in Monte Carlo simulations to impose necessary constraints on random
      functions describing partnership formation, in the new formulation all
      constraints are satisfied with probability one.

PMID- 10204390
TI  - A computer exploration of some properties of non-linear stochastic partnership
      models for sexually transmitted diseases with stages.
AB  - In this paper, branching process approximations to non-linear stochastic
      partnership models for sexually transmitted diseases in heterosexual populations
      were used to find points in the parameter space such that an epidemic would
      occur. At selected points in the parameter space, samples of Monte Carlo
      realizations of the process were computed and analyzed statistically to gain
      insights into the stochastic evolution of epidemics seeded by one infective
      single female and male. Non-linear difference equations were embedded in the
      stochastic processes, making it possible to compare trajectories computed
      according to the deterministic model with those computed from samples of Monte
      Carlo realizations. From these trajectories it was shown that stochastic
      fluctuations may have a profound effect on the long-term evolution of an
      epidemic, and examples demonstrate that an investigator may be misled if a
      deterministic model alone were used to project an epidemic, particularly when
      there is a significant probability of extinction.

PMID- 10204391
TI  - The derivation of certain pandemic bounds.
AB  - Exact results have previously been obtained concerning the spread of infection in
      continuous space contact models describing a class of multitype epidemics. The
      Pandemic Theorem gave a lower bound for the spatial final size. A discrete space
      model is considered. A simpler, more direct proof based on an infinite matrix
      formulation of the final size equations is used to obtain the pandemic result for
      this model. An upper bound is obtained, which is valid for both continuous and
      discrete space models. This enables a limiting result to be obtained for the
      spatial final size when the amount of initial infection tends to zero.

PMID- 10204392
TI  - Models for tuna school formation.
AB  - Schooling behavior is a challenging topic in the context of animal aggregation.
      It is also of economic importance for the estimation and conservation of stock
      sizes. An individual based movement model will be developed, taking into account
      energetic advantages of schooling. This model is a cellular automaton with a
      hexagonal grid. The latter considers the geometry of a school, where fish swim in
      a diamond-shape configuration in order to take advantage of the velocity, induced
      by the tail strokes of preceding fish. Furthermore, knowing the induced velocity
      field makes it possible to consider the energetic needs of fish swimming in that
      school and to describe the break up of schools due to oxygen depletion. This
      allows us to estimate maximum school sizes.

PMID- 10204393
TI  - Simulation of vessel morphogenesis using cellular automata.
AB  - We present a cellular automaton model, including lateral inhibition of an
      autocatalytic morphogen, as well as a genetic switch that differentiates tissue
      into substrate-depleting vessels. This model yields isotropic morphogenesis,
      including: dichotomous and lateral branching, blind vessel ends, and closed loops
      due to anastosmosis. The algorithm consists of a list of simple rules describing
      the essential biophysical features, permitting comfortable programming and fast
      computations. Depending on the choice of the substrate s, the model is applicable
      to leaf veins (s is auxin), insect trachea (s is CO2) or neovascularization (s is
      an angiogenesis factor). Sequential addition of rules can be correlated to
      evolutionary steps in leaf morphogenesis.

PMID- 10204394
TI  - Cytoplasm dynamics and cell motion: two-phase flow models.
AB  - The motion of amoeboid cells is characterized by cytoplasmic streaming and by
      membrane protrusions and retractions which occur even in the absence of
      interactions with a substratum. Cell translocation requires, in addition, a
      transmission mechanism wherein the power produced by the cytoplasmic engine is
      applied to the substratum in a highly controlled fashion through specific
      adhesion proteins. Here we present a simple mechano-chemical model that tries to
      capture the physical essence of these complex biomolecular processes. Our model
      is based on the continuum equations for a viscous and reactive two-phase fluid
      model with moving boundaries, and on force balance equations that average the
      stochastic interactions between actin polymers and membrane proteins. In this
      paper we present a new derivation and analysis of these equations based on
      minimization of a power functional. This derivation also leads to a clear
      formulation and classification of the kinds of boundary conditions that should be
      specified at free surfaces and at the sites of interaction of the cell and the
      substratum. Numerical simulations of a one-dimensional lamella reveal that even
      this extremely simplified model is capable of producing several typical features
      of cell motility. These include periodic 'ruffle' formation, protrusion
      retraction cycles, centripetal flow and cell-substratum traction forces.

PMID- 10204395
TI  - Graph-theoretic description of the interplay between non-linearity and
      connectivity in biological systems.
AB  - The purpose of this article is to stress the implications that the consideration
      of nonlinearity has upon the extension and strength of connectivity, if this is
      understood as a characterization of the degree of interrelation between parts of
      the system. This objective is reached within the QP formalism for non-linear
      ODEs. The formalism is developed in a graph-theoretic setting, with the help of
      which the connectionist aspect of non-linearity becomes apparent. Topology
      preserving transformations involve an exchange between the degree of non
      linearity and the strengths of interactions, thus assembling systems of
      apparently different nature into classes of equivalence. We argue that, if we
      have in mind a classification of systems according to behavior, these classes of
      equivalence should be given their proper singularity. We characterize globally
      the connectivity of a class with an index, although we point out during the
      discussion that the mathematical conception of the complex idea of connectivity
      is still incomplete.

PMID- 10204396
TI  - Probabilistic lattice models of collective motion and aggregation: from
      individual to collective dynamics.
AB  - We construct lattice gas automaton models to study collective dynamics and
      aggregation processes in biological systems. Corresponding transport equations
      are derived in appropriate space and time scaling under mean-field assumption and
      complemented with automation simulations.

PMID- 10204397
TI  - Suppression of positional errors in biological development.
AB  - Cells in developing embryos behave according to their positions in the organism,
      and therefore seem to be receiving 'positional information'. A widespread view of
      the mechanism for this is that each cell responds locally to the concentration
      level of some extracellular chemical which is distributed in a spatial gradient.
      For molecules conveying and receiving the positional signal, concentrations are
      likely to be low enough that, per individual cell, only a few thousand molecules
      may be involved. Fluctuations to be expected in these numbers (Poisson
      distribution) could readily lead to errors up to a few percent of embryo length
      in the reading of position. This is an intolerable level of error for some
      developmental pattern-forming events. Embryos must have means of suppressing such
      errors. We maintain that this requires communication between cells, and
      illustrate this by using the reaction part of two well-known Turing-type reaction
      diffusion models as the local gradient reader. We show that switching on
      diffusion in these models leads to adequate suppression of positional errors.

PMID- 10204398
TI  - Strategic and genetic models of evolution.
AB  - A new model which allows both for the effect of behavioural patterns on
      productive matings and for parental investment in the survival of offspring to
      maturity is considered. This combines ideas from genetics and evolutionary game
      theory, and provides a more realistic formulation to describe mating behaviour
      than the traditional 'battle of the sexes' model. Allowing individuals to migrate
      leads to spatial versions of both models. The saddle point method is used to
      obtain the speed of first spread of new genes/strategies in both spatial systems.

PMID- 10204399
TI  - How inbreeding and outbreeding influence the risk of extinction--a genetically
      explicit model.
AB  - We have developed a stochastic model to explore the common effect which genetics
      and demography have on the extinction risk of endangered populations. The
      dynamics is formulated as a MARKOVian birth and death process (in continuous
      time), whereby selection acts through different mortalities of each genotype.
      With the help of this model we are able to show how inbreeding and outbreeding
      can influence the genetic variability and the survival of a population. Whether
      inbreeding or outbreeding takes place depends on the specific mating system. In
      our model we consider positive assortative as well as disassortative mating. In
      the case of additive fitness we show that inbreeding reduces the extinction risk
      and the genetic variability.

PMID- 10204400
TI  - Mathematical modelling for intra-specific brood-parasitism: coexistence between
      parasite and non-parasite.
AB  - In this paper, we consider an aspect of the intra-specific brood-parasitism with
      a mathematical modelling. As in case of moorhen Gallinula chloropus, the case
      dealt with in this paper in such that just a part of the whole population has the
      parasitising behaviour against the individuals belonging to another part of non
      parasite subpopulation that does not have such behaviour. Analysing the expected
      fitness gain from the brood-parasitism, we consider the condition in order that
      parasite individuals coexist with non-parasite ones within a population. From the
      mathematical modelling analysis, it is shown that the stable equilibrium
      frequency of parasite individuals within a population, if exists, depends on the
      difference among individuals in terms of the individual quality reflected to the
      survival probability of bred offsprings.

PMID- 10204401
TI  - [Hereditary neoplastic diseases (genetic predisposition and cancer syndromes)].
AB  - After one decade of molecular genetic studies, little doubt remains that cancer
      is a genetic disease. While mutations in somatic cells may cause cancer, they
      don't carry forward to the next generation. In fact, most cancers arise in this
      way. In some individuals mutations in cancer related genes may be present at the
      constitutional level, inherited from one of the parents. An individual who
      carries a mutant allele of an inherited cancer gene has a variable risk of cancer
      that is influenced by other genetic and non-genetic factors (such as other
      cellular genes, dietary, lifestyle, and environmental factors). Collectively, the
      syndromes affect about 1% of cancer patients. During the past decade about 25
      different cancer susceptibility genes have been reported to be linked to the
      known hereditary cancer syndromes. Over the period of the last three to five
      years, studies of the specific mutations responsible for these syndromes and the
      cellular signaling pathways disrupted by the mutant proteins have begun to
      provide unprecedented insights into the molecular origin and pathogenesis of
      inherited and sporadic forms of cancer. This article reviews the cancer
      susceptibility genes and cancer syndromes, particularly those associated with
      common malignancies (breast, prostate and colorectal carcinomas). Results of the
      mutation analysis in BRCA1 and BRCA2 genes of Hungarian breast/ovarian cancer
      families will be briefly discussed. These data indicate a strong founder effect
      for some mutations of BRCA1 gene in Hungary. As a results of recent publicity of
      discoveries of molecular genetics--particularly those related to common
      malignancies--due to publicity in the scientific and the lay press awareness and
      demand for predictive DNA tests have dramatically increased worldwide over the
      past 3 years. The author, as a member of the Breast Cancer Linkage Consortium,
      shares the consensus view that genetic testing and genetic counseling for cancer
      risk together with surveillance and management should for the present be offered
      only through specialist clinical genetic departments as part of a research
      evaluation.

PMID- 10204402
TI  - [Effectiveness of pinaverium bromide therapy on colonic motility disorders in
      irritable bowel syndrome].
AB  - The special patterns of the slow wave activity in irrittable bowel syndrome by
      means of surface electromyography were examined and the effect of pinaverium
      bromide on the symptoms and on the colonic motility in this disease was
      estimated. Twenty two patients with irritable bowel syndrome and 7 healthy
      controls were selected to the study. The clinical symptoms were abdominal pain
      and bloating in all patients, constipation in 9, and diarrhoea in 6 cases.
      Surface electromyography was carried out before and on the 14th day of the
      treatment with pinaverium bromide (50 mg t. i. d). The colonic motility was
      analysed in a 2 hour fasting and a 2 hour postprandial period following a
      standard (800 kCal) meal. The slow wave frequency of 0.01-0.04 Hz were selected
      and analysed. The mean frequency of activity peaks (n/10 min) and power-index
      (area under curve, microV 10 min) were measured. For statistical analysis
      Student's t-test was applied. Electromyogram of patients with irritable bowel
      syndrome showed a significant increase of the measured colonic motility
      parameters both in fasting and postprandial states. Fourteen days of pinaverium
      bromide treatment was able to significantly reduce the intensity of the colonic
      motor activity. Administration of pinaverium bromide completely released in 6 and
      significantly improved the abdominal pain in other 12 patients, while the
      bloating disappeared in 12 and was significantly improved in 5 from 22 patients.
      Pinaverium bromide was able to normalise the stool frequency: the weekly number
      of stools was decreased from 16 to 7 in the patients complaining diarrhoea ant it
      was increased from 2 to 6 in the patients with constipation.

PMID- 10204403
TI  - [Clinical and pathologic description of stroke patients (1990-1994)].
AB  - Data relating to stroke patients at a department of internal medicine (50 beds)
      in a county teaching hospital were studied in period 1990-1994. In this five-year
      period, 1184 patients were admitted because of some forms of stroke. The
      mortality due to the stroke was 16.8% (199 patients, deceased group). Autopsy was
      performed on 159 of these 199 patients (autopsy rate: 79.8%). Age- and sex
      matched controls were selected from the survivors (n = 159). The main risk
      factors of stroke were analyzed in both groups: hypertension, cardiac events
      (decompensation, atrial fibrillation, and old myocardial infarction), previously
      verified diabetes, and recurrent stroke in the history. The mean hospital nursing
      time for the survivors was 12.3 +/- 6.3 days, while that in the deceased 7.2 +/-
      7.6 days. RESULTS: 1. Hypertension was present to similar extents in both groups
      (survivors: 82.1%, deceased group: 77.8%) 2. Decompensation occurred in 5% vs
      18.2% fibrillation in 11.3% vs 13.8%, and old myocardial infarction in 5.6% vs
      18.2% 3. Diabetes was observed in 21.3% vs 36.4% and 4. Recurrent stroke in 22.6%
      vs 39.6%. These risk factors strongly predicted the outcome of the stroke. Other
      recently observed factors (haemorrhagic form, conscious state, time of hospital
      admission, seasonal variation, higher erythrocyte sedimentation rate,
      hyperglycaemia, proteinuria, early deep vein trombosis) revealed also significant
      differences between survivors and deceased patients. Since pulmonary
      thromboembolism was twice as frequent in the deceased patients as in the
      survivors, early heparin prevention is necessary immediately after computer
      tomography which excluded the haemorrhagic type of cerebrovascular diseases.

PMID- 10204404
TI  - [Leukocyte scintigraphy in the diagnosis of acute pancreatitis].
AB  - The authors investigate the place and clinical usability of the 99mTc-HM-PAO
      leukocyte scintigraphy (LS) in patients with acute pancreatitis. Another purpose
      was to establish the diagnostic value of LS to differenciate between infected and
      noninfected pseudocysts following acute pancreatitis. Seventy-five patients with
      acute pancreatitis were examined and divided into two groups. In group 1, LS was
      performed in 46 consecutive patients in the early phase (mean 3 days following
      the beginning of the symptoms, range 1-6 days) of acute pancreatitis. In group 2,
      LS was performed in 29 patients with pancreatic pseudocysts following acute
      pancreatitis. The diagnosis of acute pancreatitis was based on the typical
      clinical symptoms, laboratory parameters, Ranson criteria, US and CT findings. In
      group 1, most of the cases with a severe clinical outcome (Ranson classification)
      gave positive LS results (13/15). Leukocyte accumulation was also detected in
      patients with mild acute pancreatitis (5/26), but at a lower frequency. The
      scintigraphic activity correlated with the leukocyte count, fever, and duration
      of hospitalization. In group 2, there were seven LS positive cases. A pancreatic
      abscess or infected pseudocyst was found in all of them during surgery. In 9 LS
      negative cases surgery and bacterial culturing revealed sterile pseudocyst. In
      conclusion, a positive LS indicated a severe course of acute pancreatitis. The
      method also seems useful for differentiation between infected and noninfected
      pancreatic pseudocysts.

PMID- 10204405
TI  - Regular claw trimming for the control of lameness--good or bad?

PMID- 10204406
TI  - Resisting resistance.

PMID- 10204407
TI  - Field exercise testing for assessing fitness in French standardbred trotters.
AB  - This review considers standardized exercise testing which is, routinely used for
      French Trotters in the field. Track testing provides a more limited range of
      measurements than treadmill testing, but has the advantage of being performed in
      the horse's natural environment. Various measurements such as heart rate during
      exercise and blood lactate concentration after exercise may be measured on the
      track and lead to the calculation of physiological variables such as V200
      (velocity corresponding to a 200 bpm heart rate) and V4 (velocity corresponding
      to a 4 mmol/L blood lactate concentration). V4 is related to the onset of blood
      lactate accumulation and relates to the aerobic capacity of the horse, as horses
      with high values for V4 have higher aerobic capacities. Although V4 is calculated
      during submaximal intensity exercise, it is related to racing performance and
      seems to be the most important measurement to assess changes in fitness. V200
      represents the cardiac capacity of the horse during exercise and is close to V4
      in mature horses. To explain further the clinical usefulness of track testing,
      and to help interpret both V4 and V200 variables, examples of exercise tests in 3
      year-old French Trotters are presented here. These results show that changes may
      occur in V4 and V200 according to different factors such as the horse's physical
      ability and either training or disease states. It underlines the importance of
      exercise tests for both trainers and veterinarians and how they may help in the
      evaluation of a horse's performance ability; in defining the intensity of a
      training program, and also in the early detection of underlying diseases.

PMID- 10204408
TI  - Molecular epidemiological studies of veterinary arboviral encephalitides.
AB  - Recent studies using molecular genetic approaches have made important
      contributions to our understanding of the epidemiology of veterinary arboviral
      encephalitides. Viruses utilizing avian enzootic hosts, such as Western equine
      encephalitis virus (WEEV) and North American Eastern equine encephalitis virus
      (EEEV), evolve as relatively few, highly conserved genotypes that extend over
      wide geographic regions; viruses utilizing mammalian hosts with more limited
      dispersal evolve within multiple genotypes, each geographically restricted.
      Similar findings have been reported for Australian alphaviruses. This difference
      may be related to vertebrate host relationships and the relative mobility of
      mammals and avians. Whereas EEEV and Venezualan equine encephalitis virus (VEEV)
      utilize small mammalian hosts in the tropics, most WEEV genotypes probably
      utilize avian hosts in both North and South America. The ability of mobile,
      infected avian hosts to disperse alphaviruses may result in continual mixing of
      virus populations, and thus limit diversification. This high degree of genetic
      conservation is also exhibited by EEE and Highlands J viruses in North America,
      where passerine birds serve as amplifying hosts in enzootic transmission foci.
      Most equine arboviral pathogens, including EEEV, WEEV and Japanese encephalitis
      virus (JEV), occur in a naturally virulent enzootic state and require only
      appropriate ecological conditions to cause epizootics and epidemics. However, VEE
      epizootics apparently require genetic changes to convert avirulent enzootic
      strains into distinct epizootic serotypes. All of these arboviruses have the
      potential to cause severe disease of veterinary and human health importance, and
      further molecular epidemiological studies will undoubtedly improve our ability to
      understand and control future emergence.

PMID- 10204409
TI  - Clinical study of toe ulcer and necrosis of the apex of the distal phalanx in 53
      cattle.
AB  - Clinical signs, causative factors, radiographic findings, type and duration of
      treatment or reason for killing were evaluated in 53 cattle (mean age: 5.3 years)
      suffering from toe ulcer and/or apical pedal bone necrosis. A total of 78 claws
      were affected. Four cattle suffered from a toe ulcer in one claw, 35 cattle
      showed osteolysis of the apex of the distal phalanx in a single claw and 14
      cattle in two or three claws per cow. Overtrimming by means of a grinding disc
      and/or perforation of the sole was diagnosed as the major cause in 27 cattle
      (49%), laminitis in 30.2% and traumatic injuries in 11.3%. Radiography revealed a
      varying degree of osteolysis involving up to two-thirds of the pedal bone. Twenty
      one cattle (39.6%) showing multiple toe disorders or involvement of one single
      claw with concurrent internal diseases were destroyed. In 23 cattle, the
      osteolytic bone was resected using a bone curette or hammer and chisel. Of these,
      the treatment was successful in 20 animals. The healing period ranged from 16-60
      days when one claw was affected and from 43-53 days when two claws were affected.
      In five cattle, the digit was amputated.

PMID- 10204410
TI  - Development of a protective immunity against Ostertagia leptospicularis in
      trickle-infected sheep and parallel changes of serum gastrin, pepsinogen and
      antibody levels.
AB  - Nine lambs, approximately 9 months of age were allocated to three groups (A, B,
      C), with three animals in each. Sheep in Groups A and B were trickle-infected
      with doses of 1000 third-stage larvae (L3) of Ostertagia leptospicularis (five
      times per week) over periods of 7.5 and 10.5 weeks, respectively, and were
      subsequently treated with fenbendazole (7.5 mg/kg). Approximately 3 weeks after
      anthelmintic treatment, all sheep were challenged with a single dose of 100,000
      L3, whereas sheep of Group C received the same dose as a primary infection. Sheep
      of Groups A and B were almost completely refractory against the challenge
      infection, as indicated by negative faecal egg counts and adult worm burdens. A
      relatively high infection level was present in the sheep of Group C. The results
      indicate that a comparatively short immunization period of 7.5 weeks is
      sufficient to protect lambs against subsequent larval challenge. During
      immunization, the pepsinogen-, gastrin- and IgA-responses were similar in the
      individual sheep. In contrast to parasite-specific IgG1 and IgG2 levels, IgA
      decreased rapidly after cessation of trickle infection and parallel anthelmintic
      treatment, and may therefore indicate current exposure to parasite antigen. After
      challenge, the majority of the immunized sheep exhibited immediate and short-term
      responses of pepsinogen, gastrin and IgA in the serum. The time course and the
      level of each of these responses were very similar in the individual sheep,
      suggesting that the release of pepsinogen, gastrin and IgA into the circulation
      was influenced by related mechanisms.

PMID- 10204411
TI  - Determinants of the maximal change in pleural pressure during tidal breathing in
      COPD-affected horses.
AB  - In six COPD-affected horses, we analysed the factors responsible for the changes
      in pleural pressure (delta Pplmax) that occur during tidal breathing. Four
      hundred-and-sixty-eight measurements of each parameter: pulmonary resistance
      (RL), dynamic elastance (Edyn), air flow rates, and the timing of breathing, were
      gathered during a trial of the bronchodilator pirbuterol. Data were placed into
      seven ranks, based on the magnitude of delta Pplmax; rank 1: 5-15; rank 2: 15-25;
      rank 3: 25-35; rank 4: 35-45; rank 5: 45-55; rank 6: 55-65; and rank 7 > 65 cm
      H2O. Up to rank 4 (45 cm H2O), the increase in delta Pplmax was due to increases
      in RL, Edyn, and inspiratory and expiratory air flow rates. Further increases in
      delta Pplmax were due to continuing increases in Edyn and flow rates with little
      change in resistance. The increase in inspiratory flow rates was the result of a
      decrease in inspiratory time. The large increase in peak expiratory flow could
      not be explained by the small decrease in expiratory time and must therefore be
      due to a change in breathing strategy as delta Pplmax increased. Changes in air
      flow rates as well as changes in RL and Edyn must be considered as reasons for a
      change in delta Pplmax when evaluating horses with COPD.

PMID- 10204412
TI  - The effect of cyclic temperatures on the growth of Fasciola hepatica and Lymnaea
      viatrix.
AB  - The experiment aimed to measure the effect of constant and variable temperatures
      on the growth of Lymnaea viatrix snails, on the development of a Peruvian isolate
      of Fasciola hepatica eggs and on the development of F. hepatica in the snails.
      This was carried out by cultivating infected and uninfected snails and fluke eggs
      in artificial, temperature controlled chambers. L. viatrix snails were found to
      develop at a rate dependent on environmental temperature, but developed at least
      as well under conditions of varying temperature as at the same mean constant
      temperature. F. hepatica eggs held at constant or varying temperatures, developed
      at a rate comparable to other reports. However, eggs developing at varying
      temperatures appeared to have reduced hatchability. Parasite development within
      the snails was slow, though within the limits calculated from the literature, and
      varying temperature did not appear to reduce development compared to constant
      temperatures.

PMID- 10204413
TI  - The effects of a post partum injection of prostaglandin F2 alpha on return to
      oestrus and pregnancy rates in dairy cows.
AB  - The interval from calving to conception is unnecessarily long in dairy cows. Post
      partum administration of prostaglandin F2 alpha can reduce the calving to
      conception interval, but it is not known whether this is due to advanced return
      to oestrus, increased oestrus intensity and/or increased pregnancy rates. In two
      experiments, the treatment of dairy cows with prostaglandin F2 alpha 21 days post
      partum reduced the interval to first oestrus and first service by about 10 days.
      The intensity of oestrus was not affected. Pregnancy rates to first service were
      increased from (on average) 60 to 80%, and the number of services/conception was
      reduced from 2.0 to 1.3.

PMID- 10204415
TI  - Temporal variations in blood glutathione peroxidase (GSHPx) activity in sheep at
      pasture in a Mediterranean area.
AB  - The present study evaluates blood GSHPx activity in 18 sheep flocks at range, to
      identify those seasons with the highest risk of selenium deficiency. Samples were
      taken from 1108 15-day-old lambs during the two usual lambing periods in this
      geographical area (autumn-winter and spring-summer). The overall mean values in
      the first period (146.69 +/- 3.41 i.u./g Hb) was higher than in the second one
      (107.50 +/- 3.53 i.u./g Hb). This may be explained by the special features of the
      climate in the Mediterranean area, which allow an optimum growth of grass from
      October to May. Therefore, the lambs born in spring-summer are from pregnancies
      in months when feeding is based only upon grazing. However, lambs born in autumn
      winter comes from ewes gestating during the summer, when supplementation with
      cereal grains is given. As a conclusion, lambs born in spring-summer in this area
      are at higher risk to selenium-deficiency related disorders.

PMID- 10204414
TI  - Development of goitre and enterohepatonephropathy in Nubian Goats fed with pearl
      millet (Pennisetum typhoides).
AB  - We present the first reported study of Pearl millet (Pennisetum typhoides)
      goitrogenesis and enterohepatonephropathy in 5-9-month-old Nubian goats of either
      sex. The goats were fed 0.25 or 1 g millet per kg body weight per day for 62
      days. The effects on thyroid follicles, intestines, liver and kidneys are
      described and correlated with clinical signs, changes in serum and tissue iodine
      and selenium concentrations and alterations in serum aspartate transaminase,
      gamma glutamyl transferase, total protein, total lipids and other constituents
      and haematological values.

PMID- 10204416
TI  - The effect of short duration transportation on serum cortisol response in alpacas
      (Llama pacos).
AB  - This research project evaluated the changes in serum cortisol in six male and six
      female alpacas in response to transportation of short duration. All alpacas were
      subjected to trailer transportation for 30 min. Serum samples were obtained prior
      to transportation, immediately after transportation, and after a 4-h recovery
      period. Heart rate was recorded at each time interval and observations of
      individual behavioural characteristics were recorded. Data were analysed using
      analysis of variance. Heart rate was not significantly changed by transportation
      stress. Serum cortisol concentration was significantly higher after
      transportation, but head returned to baseline concentration after the 4-h
      recovery period. Behavioural characteristics were not associated with changes in
      serum cortisol concentration.

PMID- 10204417
TI  - An anatomical study of the internal genital organs of the yak at different ages.
AB  - Forty-five female yaks of different ages with known reproductive histories were
      used to determine the anatomical characteristics of their internal genital
      organs. The results showed that there were several follicles of different sizes
      present on the surface of each examined ovary, up to a maximum of 13. In each age
      group, a greater number of follicles < 5 mm was observed in the right than in the
      left ovary (P < 0.05), while the number of follicles > 5 mm in the right ovary
      was almost the same as that in the left one. The average sizes and/or weights of
      the ovary, oviduct and uterus became larger or heavier with increasing age, and
      significant differences occurred between age groups (P < 0.05). The shapes,
      locations and other anatomical characteristics of the different internal genital
      organs are also described.

PMID- 10204418
TI  - Ovarian morphology and follicular systems in yaks of different ages.
AB  - Forty-five female yaks of different ages with known reproductive histories were
      used to determine the morphology and follicular systems of their ovaries. The
      histological structure of the ovaries in each age group was found to be similar
      and resembled that of cattle and buffalo. The atresia of primordial follicles
      took one form (oocyte atresia); that of growing follicles could be divided into
      two stages (early and late); and that of Graafian follicular were classified as
      early, definite and late stage. The details of the several types of atresia are
      described herein. The average total numbers of primordial follicles per ovary
      pair in 1-month-old calves, 1-year-old heifers, 2-year-old heifers and 7-10-year
      old cows were 53,500 +/- 6300, 32,870 +/- 4500, 22,850 +/- 2800 and 9500 +/-
      1200, respectively; those of growing follicles were 210 +/- 76, 815 +/- 95, 895
      +/- 142 and 445 +/- 88, respectively; and those of Graafian follicles were 36.5
      +/- 14.2, 41.7 +/- 12.3, 37.8 +/- 9.8 and 42.5 +/- 14.5, respectively. The
      percentage of atretic primordial follicles per ovary pair in 1-month-old calves,
      1-year-old heifers, 2-year-old heifers and 7 to 10 year-old cows were 51.6, 55.5,
      56.7 and 47.4%, respectively. The average total numbers of atretic growing
      follicles per ovary pair were 119.5 +/- 21.5, 605.5 +/- 74.3, 721.6 +/- 78.5 and
      275.8 +/- 66.3, respectively; those of atretic Graafian follicles were 22.1 +/-
      5.6, 21.2 +/- 7.6, 21.5 +/- 4.7 and 25.3 +/- 6.7, respectively.

PMID- 10204419
TI  - A procedure to determine the individually comfortable position of visual displays
      relative to the eyes.
AB  - In an intervention phase, 38 operators used four different imposed screen
      positions (near versus distant, high versus low) for a full working day to
      experience the advantages and disadvantages. Screens at about 66 cm induced more
      reported strain than screens at about 98 cm. When operators later freely selected
      their individually most comfortable screen position, individually different
      changes due to the intervention were observed: some subjects changed to shorter,
      others to longer viewing distances, some operators adjusted the screen lower,
      others higher. These effects were confirmed in repeated tests. Thus, trying out
      different screen positions appears useful for arranging the VDU workstation to
      the individually most comfortable screen location relative to the eyes.

PMID- 10204420
TI  - Effect of carpal tunnel syndrome on grip force coordination on hand tools.
AB  - This study investigated coordination of the grip force on and force applied with
      a hand tool using a precision pinch grip. A simulated hand tool was developed to
      measure grip force exerted on the tool as a function of the force transmitted
      from the tool to an external object in a dynamic force matching paradigm. Grip
      force coordination measures reflected subjects' abilities to modulate grip force
      in parallel with the tool application force and their abilities to minimize
      excessive grip force. These measures were calculated for seven subjects with a
      diagnosis of carpal tunnel syndrome (CTS) and seven age- and gender-matched
      controls. The absolute magnitude of excessive grip force (safety margin) was
      unreliable because of the high intrasubject variability in coefficient of
      friction measurements. Linear regression equations predicting coefficient of
      friction from pinch force magnitude had low r2 coefficients of determination and
      were generally not statistically significant (p > 0.05). Relative comparisons of
      grip force control showed that individuals with CTS exhibited a statistically
      significant (p < 0.05) increase in ratio of grip force to application force (54%
      higher than controls) and a significant (p < 0.05) decrease in modulation of
      pinch force with application force (12% lower than controls). These results
      suggest that individuals with CTS lose some ability to coordinate efficiently
      grip force on hand tools and exert higher grip forces on tools, at equivalent
      application forces, than controls. This is believed to be a result of tactile
      sensibility deficits associated with CTS. As a result, workers with CTS may be at
      increased risk of accelerating the progression of their musculoskeletal disorder.

PMID- 10204421
TI  - The influence of work characteristics on the need for recovery and experienced
      health: a study on coach drivers.
AB  - Work characteristics, occupationally-induced fatigue, and health complaints were
      investigated on the basis of questionnaire data from 363 randomized coach
      drivers. The hypothesis was tested that, apart from high job demands and low job
      control, need for recovery is an indicator of occupationally-induced health
      complaints. Multiple linear regression analyses showed that need for recovery was
      a major predictor of psychosomatic complaints, sleep complaints, and complaints
      of emotional exhaustion in coach drivers. The influence of job demands and job
      control on health problems was moderately confirmed. The results of this study
      draw attention to the role of the need for recovery, as a sign of occupationally
      induced fatigue and predictor of health complaints, in future research on
      occupational stress.

PMID- 10204422
TI  - Physiological strain during kitchen work in relation to maximal and task-specific
      peak values.
AB  - Six female and three male subjects from a hospital kitchen volunteered for the
      study. The subjects were working on a conveyor belt collecting and sorting dirty
      plates, glasses and cutlery for cleaning. In the study, a medical examination, a
      maximal clinical exercise test with a 12-lead electrocardiogram (ECG) and a
      maximal arm cranking test were performed in the laboratory. Further, each subject
      was studied for 30 min during a normal work shift in the kitchen. Oxygen uptake
      (VO2) and heart rate (HR) were continuously registered. During the work period, a
      rating of perceived exertion (RPE) was asked at the 5th, 15th and 30th minute.
      Physiological responses were measured by a portable system (K4) both in the
      laboratory and in the field. VO2 and HR measured in the field were proportioned
      to corresponding maximal values during cycling and to peak values during arm
      cranking. The mean VO2 for the male and the female subjects during kitchen work
      was 0.65 +/- 0.16 l min-1. This corresponded to 24% of VO2max and to 41% of
      VO2peak during arm-cranking. The difference was significant (p < 0.001). Owing to
      a magnetic field at the conveyor belt, reliable HR values were obtained only from
      the female subjects. The mean HR during work among the female subjects was 101
      beats min-1. It corresponded to 55% of HRmax and 67% of HRpeak during arm
      cranking (p < 0.05). The present study shows that the relative work intensity is
      markedly higher when it is expressed relative to the corresponding muscle group's
      VO2peak instead of the VO2max. Similar difference was also seen in the HR
      response. More task-specific testing of physical capacity may provide improved
      evaluation of physical strain in a job.

PMID- 10204424
TI  - Bracket design and grades of service.

PMID- 10204423
TI  - Effect of sleep loss on core temperature when movement is controlled.
AB  - Nine subjects were studied for 16 days in an isolation unit where they lived on
      normal time, working at a decision-making, computer-driven task during the
      daytime. Interspersed among these control days were three occasions when sleep
      was curtailed. Rectal temperature and activity (non-dominant wrist) were measured
      throughout. Any effects of sleep loss on core temperature and activity were
      assessed by comparing these variables on control days with values during the
      daytime immediately following sleep loss, and during the next (recovery) day.
      During the daytime following sleep loss, activity showed no significant changes.
      By contrast, core temperature was significantly lower, particularly after the
      night of complete sleep loss. On recovery days also, activity was not
      significantly changed from control days but core temperatures during work were
      significantly lower than on control days if there had been no sleep the previous
      night. These results indicate that the effects of sleep loss on core temperature
      can persist for at least 24 h, and that they occur in the absence of parallel
      changes in activity.

PMID- 10204425
TI  - Anomalous dental morphology and root resorption during orthodontic treatment: a
      pilot study.
AB  - The present study investigated the relation between anomalous dental morphology
      and root resorption during orthodontic treatment. One hundred and eleven sets of
      orthodontic records (a total of 1,630 teeth) were examined. Root resorption was
      determined from post-treatment panoramic radiographs using a five-grade
      quantitative measurement. It was found that patients with short or blunt roots
      before treatment underwent significant root shortening during orthodontic
      treatment. Patients with any one dental anomaly had a significantly higher degree
      of root resorption compared with patients with no dental anomaly. Invaginated
      teeth, teeth with thin or pipette-shaped roots and teeth with short or blunt
      roots were likely to be more susceptible to root resorption than those without
      such anomalies. Possible linkages between the aetiological factors of dental
      anomalies and the susceptibility to root resorption were discussed. The presence
      of anomalous dental morphology should be taken into account in orthodontic
      treatment planning.

PMID- 10204426
TI  - Craniofacial morphology in Chinese and Swedish children with Angle Class I and
      Class II occlusal relations.
AB  - The purpose of this study was to compare the craniofacial morphology of a group
      of Chinese children from northern China with a group of Swedish children. Each
      ethnic group comprised 20 boys and 20 girls with Class I occlusion, and 20 boys
      and 20 girls with Class II occlusion. The ages of the children ranged from eight
      to ten years. Lateral cephalometric radiographs were used for the recording of a
      number of skeletal, dental, nasopharyngeal airway, and hyoid bone variables. The
      results of the comparisons of the two ethnic groups showed that the antero
      posterior dimensions of the anterior cranial base and the maxilla in the Chinese
      children were significantly smaller than the corresponding dimensions in the
      Swedish children. The mean values of anterior and posterior face heights,
      inclination of the upper incisors, and protrusion of the lower incisors, were
      significantly greater in the Chinese than in the Swedish samples. In the median
      plane, the size of the nasopharyngeal airway was significantly greater in the
      Chinese than in the Swedes. This difference was due to the fact that the soft
      tissues covering the posterior nasopharyngeal wall were thinner in the Chinese
      children than in the Swedish children. In general, the ethnic differences were
      the same in the Class I and the Class II groups. The differences in some of the
      dental and skeletal characteristics found between northern Chinese and Caucasian
      children are similar to previously described differences between southern Chinese
      and Caucasian children.

PMID- 10204427
TI  - The reproducibility of cephalometric landmarks: an experimental study on skulls.
AB  - Few previous cephalometric studies have used dry skulls in order to eliminate the
      effects of the facial soft tissues. The aim of this study were to quantify the
      intra-examiner reproducibility of the commonly used cephalometric landmarks,
      angles and distances, using dry skulls and to compare these errors with previous
      error data obtained from normal cephalograms of living patients. Thirty skulls
      were mounted in a purpose-designed holder and repeat cephalograms of each skull
      were recorded and digitised. All measurements were made relative to an X-Y
      coordinate reference grid. Scattergrams were produced to show the characteristic
      distribution of the intra-examiner reproducibility errors for the landmarks, and
      the reproducibility of the angles and distances were tabulated. This data was
      compared with a related study that included the soft tissue profile. The standard
      deviations of the skeletal and dental angles and distances were greater in the
      presence of the soft tissues. These differences were up to four times larger for
      measurements including the location of Nasion (e.g. SNA, SNB and SNPg), which was
      the landmark location most affected by the presence of soft tissues, and for the
      distance: Incisal tip of Lower Incisor to Pogonion. Anterior Nasal Spine, in the
      horizontal plane, was also greatly affected by the presence of the soft tissues.
      By using dry skulls, the errors observed in this study may serve as standards for
      the rational interpretation of clinical cephalometric values.

PMID- 10204429
TI  - Activator and Begg appliance management of a severe Angle Class II, division 1
      malocclusion.
AB  - A male patient aged 12 years 11 months presented with the chief complaint of
      prominent, spaced upper teeth and was keen to overcome his dental problem.

PMID- 10204428
TI  - A twelve-month clinical trial comparing the bracket failure rates of light-cured
      resin-modified glass-ionomer adhesive and acid-etch chemical-cured composite.
AB  - A clinical study was undertaken to compare the failure rate over a twelve-month
      period of orthodontic brackets bonded with a light-cured resin-modified glass
      ionomer (Fuji Ortho LC-GC International Japan) and an acid-etch chemically-cured
      two-paste composite (Orthodontic Concise-3M USA). Failure rates of 6.1 per cent
      and 5.4 per cent respectively were reported, with no statistically significant
      difference between the two adhesives. This finding, along with the relative ease
      of use and possible advantages of reduced risk of peri-bracket demineralisation,
      suggests that the resin-modified glass-ionomer adhesive may become more popular
      as a bracket adhesive.

PMID- 10204430
TI  - Distraction osteogenesis in a patient with micrognathia and a rare facial
      clefting syndrome.

PMID- 10204431
TI  - Lifelong Learning. 16th Australian Orthodontic Congress. Canberra, 22-26 March
      1998. Abstracts.

PMID- 10204432
TI  - Full buccal segment control as a routine treatment objective.

PMID- 10204433
TI  - OPG radiation dosages.

PMID- 10204434
TI  - Nd:YAG and CO2 laser therapy of oral mucosal lesions.
AB  - OBJECTIVE: Experiences gained in the management of oral mucosal lesions by CO2
      and Nd:YAG laser therapy in an outpatient clinic treated over an 80-year period
      are described. SUMMARY BACKGROUND DATA: Lasers have indications for use in
      dentistry for incision, excision, and coagulation of intraoral soft tissue.
      Advances in laser technology have provided delivery systems for site-specific
      delivery of laser energy with short interaction items on tissue to be ablated.
      This study retrospectively evaluates a series of clinical case studies. METHODS:
      Sixty-four patients with a variety of benign oral soft tissue lesions were
      treated by laser excision. Thirty-five patients were treated by a pulsed
      fiberoptic delivered Nd:YAG contact laser, and 29 by a continuous free-beam CO2
      non-contact laser. The largest group of lesions treated were leukoplakia (39
      cases). Other lesions excised and biopsied were lichen planus, squamous
      papilloma, pyogenic granuloma, focal melanosis, nonhealing traumatic ulceration,
      hemangioma, and lymphangioma. All patients were followed postoperatively (mean
      6.8 months, range 1-36 months). RESULTS: Laser excision was well tolerated by
      patients with no intraoperative or postoperative adverse effects. All patients
      healed postsurgically with no loss of function. CONCLUSIONS: CO2 and Nd:YAG
      lasers are successful surgical options when performing excision of benign
      intraoral lesions. Advantages of laser therapy include minimal postoperative
      pain, conservative site-specific minimally invasive surgeries, and elimination of
      need for sutures.

PMID- 10204435
TI  - Study of microleakage at Class I cavities prepared by Er:YAG laser using three
      types of restorative materials.
AB  - OBJECTIVE: The purpose of this in vitro study were to investigate microleakage at
      class I cavities filled with amalgam, composite resin, or glass-ionomer after
      preparation by Er:YAG laser and to compare the results with those by a
      conventional method using an air turbine. SUMMARY BACKGROUND DATA: There has been
      no report of a study of microleakage on class I cavities prepared by Er:YAG
      laser. METHODS: Ninety-six extracted human premolar and molar teeth were used in
      this study. Forty-eight class I cavities were prepared by Er:YAG laser and 48
      class I cavities by air turbine. After preparation, each of the 2 groups was
      further subdivided into 3 groups, respectively, and cavities in each of these
      subgroups were filled by 1 of 3 types of restorative materials. Microleakage at
      the restored cavities was assessed by the dye penetration method and scanning
      electron microscopy (SEM). RESULTS: Minimal or moderate leakage was evident at
      most of the composite resin or glass-ionomer restorations, whereas moderate or
      severe leakage was observed at most of the amalgam restorations as shown by the
      dye penetration method. There was significant difference among the 3 restorative
      materials (p < 0.05), but there was no significant difference in microleakage
      between the cavities prepared by Er:YAG laser and those by air turbine (p >
      0.05). SEM evaluation demonstrated good adaptation with most of the composite
      resin or glass-ionomer restorations, but amalgam restorations showed slightly
      poorer adaptation. CONCLUSION: These results suggest that Er:YAG laser is useful
      for class I cavity preparation from the viewpoint of microleakage.

PMID- 10204436
TI  - Carboxyhemoglobinemia due to peritoneal smoke absorption from laser tissue
      combustion at laparoscopy.
AB  - OBJECTIVE: The carbon monoxide (CO) smoke component from tissue pyrolysis was
      evaluated for peritoneal absorption in patients undergoing laparoscopy to
      determine its effects and ability to be detected in peripheral blood. SUMMARY
      BACKGROUND DATA: Previous studies have demonstrated changes in peripheral
      methemoglobin levels as a result of peritoneal absorption of laser smoke.
      METHODS: Fifty patients had preoperative, intraoperative, and postoperative
      levels of carboxyhemoglobin (COHb) and pulse oximetry evaluated. The control
      group (25) had no laser or cautery used and the study group (25) had carbon
      dioxide laser used during the laparoscopic procedures. RESULTS: The control group
      showed no change in COHb, or intra-abdominal CO levels, before, during, and after
      the procedures, and no change in blood CO or pulse oximetry reading. The laser
      smoke group showed a statistically significantly elevated (p < .05) peripheral
      blood COHb levels, a significant increase in intra-abdominal CO concentration,
      and a lack of correlation of pulse oximetry and blood oxygen saturation
      experiments. CONCLUSIONS: CO is created in extremely large quantities during
      laser use at laparoscopy and is absorbed through the peritoneal cavity. Symptoms
      of smoke poisoning can be seen with these elevations. Continuous or intermittent
      removal of smoke produced from laser use is recommended.

PMID- 10204437
TI  - Effects of diclofenac sodium and He:Ne laser irradiation on plasmatic fibrinogen
      levels in inflammatory processes.
AB  - OBJECTIVE: The aim of the present work was to determine the possible synergic
      effect on the concentration of plasma fibrinogen (PF) by injecting diclofenac
      sodium associated with laser therapy postsurgery. SUMMARY BACKGROUND DATA:
      Nonsteroidal anti-inflammatory drugs (NSAIDs) and He:Ne laser irradiation as a
      therapy were used to inhibit the effects generated by inflammation. Tissue injury
      produces significant increases in PF levels, which are reduced to normal values
      by administration of NSAIDs or laser irradiation of the injured zone. MATERIALS
      AND METHODS: Rate were divided into groups in which different presurgical and
      postsurgical treatment were used; the inflammation was induced by laparotomy.
      RESULTS: Parenteral diclofenac or He:Ne laser irradiation used separately in
      normal rats did not produce changes in the PF levels. Diclofenac and laser
      irradiation combined postsurgery produced a significant reduction of PF levels
      compared with normal values, or with groups that were injected or irradiated
      postsurgically. CONCLUSION: The inflammatory response could be reduced by the
      effect of the diclofenac sodium upon the COX-2/COX-1 inhibitory relation
      associated with the photobiological effect of the He:Ne laser.

PMID- 10204438
TI  - Result of laser-assisted disc ablation after unsuccessful percutaneous disc
      decompression.
AB  - OBJECTIVE: The author assessed results of laser-assisted disc decompression
      (LADA) in patients who already had earlier unsuccessful percutaneous discectomy
      (PD) at the same level. SUMMARY BACKGROUND DATA: The efficacy of LADA after
      failed PD for the same disc level is not well established. However the literature
      does not suggest any contraindication to performing LADA in previously failed PD.
      METHODS: Prospective study of LADA after failed PD at the same disc level in 15
      patients was done. Results were assessed clinically using the Japanese
      Orthopaedic Association (JOA) scale for an average follow up of 13 months.
      RESULTS: No patient had excellent recovery, 7 patients had poor recovery, 5
      patients had fair recovery, and only 3 patients had good recovery. None of the
      patients had worsening of symptoms after the LADA. CONCLUSIONS: Repetition of
      another form of minimally invasive surgery by laser (Neo:Yag) for the same level
      of disc herniation after unsuccessful PD has low rate of success.

PMID- 10204439
TI  - Percutaneous laser disc decompression (PLDD): twelve years' experience with 752
      procedures in 518 patients.
AB  - BACKGROUND AND OBJECTIVE: Percutaneous laser disc decompression (PLDD) is a
      procedure in which herniated intervertebral discs are treated by reduction of
      intradiscal pressure through laser energy. This is introduced by a needle
      inserted into the nucleus pulposus under local anesthesia and fluoroscopic
      monitoring. The small volume of nucleus vaporized results in a sharp fall of
      intradiscal pressure, with consequent migration of the herniation away from the
      nerve root. First proposed by the author in 1984, this concept was validated by 2
      years of in vitro experiments. Our aim was to apply this concept to a large
      series of patients with herniated disc disease. STUDY DESIGN/MATERIALS AND
      METHODS: A nonrandomized, nonblinded study was conducted in male and female
      patients with symptomatic, image-documented intervertebral herniated discs in a
      12-year period using PLDD as the only treatment modality. RESULTS: The author's
      own series consists of 752 intervertebral discs in 518 patients over a period of
      12 years. The overall success rate ranged from 75% to 89% with a complication
      rate of less than 1%. CONCLUSION: PLDD has proven to be safe and effective. It is
      minimally invasive, is performed in an outpatient setting, requires no general
      anesthesia, results in no scarring or spinal instability, reduces rehabilitation
      time, is repeatable, and does not preclude open surgery should that become
      necessary.

PMID- 10204440
TI  - Why two, kay?

PMID- 10204441
TI  - Laser and curing light induced in vitro pulpal temperature changes.
AB  - OBJECTIVE: This study was conducted to compare in vitro pulp chamber temperature
      changes induced by conventional curing light and argon laser under common
      conditions. SUMMARY BACKGROUND DATA: Previous in vitro studies have shown that
      impacting the surface of teeth with either an argon laser or conventional curing
      light causes pulp temperature increases of various degrees. METHODS: The sample
      tooth had a class V composite restoration placed with 2.48-mm distance from the
      surface of the composite to a Thermister Thermometer. The thermometer was
      inserted into the cutaway pulp chamber to measure the temperature increase from
      stabilized room temperature, which was caused by exposure to argon laser or
      conventional curing light. RESULTS: Temperature increases for the argon laser for
      the recommended curing time were 3 degrees F or less. The longer the exposure
      times for either method of curing, the higher the temperature increased.
      CONCLUSION: At recommended curing times, in vitro pulp chamber temperature
      increases from laser units were significantly lower than those of the
      conventional curing lights.

PMID- 10204442
TI  - Morphological changes of human teeth with Er:YAG laser irradiation.
AB  - OBJECTIVE: The purpose of this study was to investigate morphological changes in
      human enamel and dentin structures irradiated with the use of an Er:YAG laser.
      SUMMARY BACKGROUND DATA: Despite the high number of research projects concerned
      with digital applications of lasers, few studies have targeted the effects of
      Er:YAG laser irradiation on human enamel or dentin structures. METHODS: Enamel
      and dentin surfaces of 40 extracted human teeth were irradiated for 5 seconds
      with a 2.94 microns wavelength, at an output of 300 mJ. Histological and scanning
      electron microscope studies were then performed to determine the morphological
      changes in the enamel and dentin structures of those teeth. RESULTS: The Er:YAG
      laser beam produced defects without signs of serious thermal damage to enamel or
      dentin. Undesirable thermal effects such as surface cracking or carbonization
      were not observed. Histological examinations revealed the presence of a thin
      basophilic line at the bottom and along the walls of defects in the dentin. These
      morphological changes were evidence of minimal thermal damage to surrounding
      tissue. CONCLUSIONS: These findings suggest that it is possible to remove the
      enamel and dentin using Er:YAG laser irradiation with minimal thermal changes.
      However, the mechanism involved in the ablation of enamel and dentin by Er:YAG
      laser irradiation has not been clarified in this study. Therefore, more research
      is necessary before the Er:YAG laser can be used clinically in the future.

PMID- 10204443
TI  - Removal of orthodontic bonding resin residues by CO2 laser radiation: surface
      effects.
AB  - OBJECTIVE: The purpose of this in vitro study was to evaluate the potential use
      of pulsed CO2 laser radiation to remove selectivity residues of orthodontic
      bonding resin that remain after debonding of fixed orthodontic appliances.
      SUMMARY BACKGROUND DATA: Current techniques used for removal of orthodontic
      bonding resin after removal of fixed appliances include rotary instruments,
      debonding pliers, and ultrasonic scalers. These techniques, however, are time
      consuming and inefficient, and may damage tooth enamel. METHODS: A standardized
      cylinder of orthodontic bonding resin was bonded to the buccal surfaces of 100
      extracted premolar teeth, which were then divided into 10 groups of 10 specimens
      each. In 9 groups, the resin was ablated using 1 of 9 different laser parameters,
      while in the remaining control group, the resin was removed with a slow speed
      tungsten carbide bur. Specimens were evaluated by light microscopy and scanning
      electron microscopy (SEM) to assess the amount of resin remaining and the extent
      of the damage to the underlying enamel. RESULTS: The 2 W/100 ms combination was
      optimal, with a high efficiency of resin removal and the least enamel damage.
      Higher laser powers increased the extent of enamel damage without enhancing resin
      removal. CONCLUSIONS: This laser technique appears promising, however, further
      studies of the extent of thermal changes at the level of the dental pulp are
      necessary to establish more fully the risk-benefit ratio.

PMID- 10204444
TI  - Morphological and atomic analytical changes of root canal wall dentin after
      treatment with thirty-eight percent Ag(NH3)2F solution and CO2 laser.
AB  - OBJECTIVE: The morphological and atomic analytical changes of the root canal wall
      dentin, treated with 38% diamine silver fluoride [Ag(NH3)2F] solution and
      irradiated by carbon dioxide (CO2) laser at the continuous wave mode were
      evaluated in vitro. SUMMARY BACKGROUND DATA: There has been no report on the
      morphological or atomic analytical changes of the effect of Ag(NH3)2F solution
      and CO2 laser on root canal walls. METHODS: Eighty extracted human single-rooted
      teeth were instrumented using a conventional technique and randomly divided into
      8 groups of 10 teeth each. The teeth in group 1 were neither treated with
      Ag(NH3)2F solution nor lased. Groups 2, 3, and 4 were irradiated by laser at the
      parameters of 1, 2, and 3 W for 10 seconds, respectively. Group 5 was treated
      with Ag(NH3)2F solution only. The other 3 groups were treated with Ag(NH3)2F
      solution and then lased by the same method as groups 2, 3, and 4. After this
      treatment, 4 specimens each from group 1, 5, and 6 were analyzed by scanning
      electron microscope-energy dispersive x-ray spectroscopy (SEM-EDX) and other
      specimens in all groups were examined by scanning electron microscopy (SEM).
      RESULTS: The smear layer and debris of the control and lased specimens were not
      completely removed, but the areas of carbonization of evaporation of smear layer
      and open dentinal tubules were observed on the specimens treated with Ag(NH3)2F
      and lased at 1 W (group 6). After laser irradiation, the amount of silver on the
      root canal surfaces was significantly reduced to approximately one-third level on
      the measurement of SEM-EDX (p < 0.01). CONCLUSION: These results suggest that CO2
      laser is an effective method to remove or melt smear layer of root canal walls
      after treatment with 38% Ag(NH3)2F solution if an appropriate parameter is
      selected.

PMID- 10204445
TI  - Early relief of erectile dysfunction after laser decompression of herniated
      lumbar disc.
AB  - OBJECTIVE: The use of percutaneous laser disc decompression (PLDD) for the
      treatment of erectile dysfunction caused by herniated disc disease is described.
      SUMMARY BACKGROUND DATA: Disc herniation is often overlooked as a cause of
      erectile dysfunction, with few cases reported in the literature. METHODS: Two
      patients with erectile dysfunction were treated with PLDD as outpatients.
      RESULTS: In addition to the early return of erectile function in both cases,
      immediate pain relief was achieved in the second case. Follow-up visits confirmed
      continued normal sexual function and lack of pain. CONCLUSIONS: The literature
      now includes 23 cases well-documented cases of erectile dysfunction caused by
      spinal cord disc herniation. PLDD is a minimally invasive procedure that that can
      be used to treat herniation of intervertebral discs, which has been found to
      cause erectile dysfunction.

PMID- 10204446
TI  - Low power laser therapy and analgesic action.
AB  - OBJECTIVE: The semiconductor or laser diode (GaAs, 904 nm) is the most
      appropriate choice in pain reduction therapy. SUMMARY BACKGROUND DATA: Low-power
      density laser acts on the prostaglandin (PG) synthesis, increasing the change of
      PGG2 and PGH2 into PG12 (also called prostacyclin, or epoprostenol). The last is
      the main product of the arachidonic acid into the endothelial cells and into the
      smooth muscular cells of vessel walls, that have a vasodilating and anti
      inflammatory action. METHODS: Treatment was performed on 372 patients (206 women
      and 166 men) during the period between May 1987 and January 1997. The patients,
      whose ages ranged from 25 to 70 years, with a mean age of 45 years, suffered from
      rheumatic, degenerative, and traumatic pathologies as well as cutaneous ulcers.
      The majority of patients had been seen by orthopedists and rheumatologists and
      had undergone x-ray examination. All patients had received drug-based treatment
      and/or physiotherapy with poor results; 5 patients had also been irradiated with
      He:Ne and CO2 lasers. Two-thirds were experiencing acute symptomatic pain, while
      the others suffered long-term pathology with recurrent crises. We used a pulsed
      diode laser, GaAs 904 nm wavelength once per day for 5 consecutive days, followed
      by a 2-day interval. The average number of applications was 12. We irradiated the
      trigger points, access points to the joint, and striated muscles adjacent to
      relevant nerve roots. RESULTS: We achieved very good results, especially in cases
      of symptomatic osteoarthritis of the cervical vertebrae, sport-related injuries,
      epicondylitis, and cutaneous ulcers, and with cases of osteoarthritis of the
      coxa. CONCLUSIONS: Treatment with 904-nm diode laser has substantially reduced
      the symptoms as well as improved the quality of life of these patient, ultimately
      postponing the need for surgery.

PMID- 10204447
TI  - Classification, diagnostic criteria, and treatment recommendations for orofacial
      manifestations in HIV-infected pediatric patients. Collaborative Workgroup on
      Oral Manifestations of Pediatric HIV Infection.
AB  - The criteria for diagnosis of HIV-related oral lesions in adults are well
      established, but corresponding criteria in the pediatric population are not as
      well defined. The Collaborative Workgroup on the Oral Manifestations of Pediatric
      HIV infection reached a consensus, based upon available data, as to the
      presumptive and definitive criteria to diagnose the oral manifestations of HIV
      infection in children. Presumptive criteria refer to the clinical features of the
      lesions, including signs and symptoms, whereas definitive criteria require
      specific laboratory tests. In general, it is recommended that definitive criteria
      be established whenever possible. Orofacial manifestations have been divided into
      three groups: 1) those commonly associated with pediatric HIV infection; 2) those
      less commonly associated with pediatric HIV infection; and 3) those strongly
      associated with HIV infection but rare in children. Orofacial lesions commonly
      associated with pediatric HIV infection include candidiasis, herpes simplex
      infection, linear gingival erythema, parotid enlargement, and recurrent aphthous
      stomatitis. In contrast, orofacial lesions strongly associated with HIV infection
      but rare in children include Kaposi's sarcoma, non-Hodgkin's lymphoma, and oral
      hairy leukoplakia. Treatment recommendations, specific for this age group, have
      been included for some of the more common HIV-related orofacial manifestations.

PMID- 10204448
TI  - Management of gingival overgrowth associated with generalized enamel defects in a
      child.
AB  - Gingival overgrowth is usually associated with systemic conditions or treatment
      (e.g. blood dyscrasias, anti-epileptic or immunosuppressive agents). A child is
      presented, who had enlarged gingiva associated with a generalized enamel defect
      (amelogenesis imperfecta (AI), hypoplastic type) and document the periodontal and
      restorative management of this case.

PMID- 10204449
TI  - Reframing--reappraising an old behavioral technique.
AB  - Successful reframing converts notions of unpleasantness to notions that are
      acceptable to the parties involved. However, the basic precursor to successful
      reframing is that the message conveyed must be consistent with the individuals
      'meta' way of thinking and consistent with concepts of reality.

PMID- 10204450
TI  - The current status of dentistry, particularly pediatric dentistry, among the
      countries and territories of Asia.
AB  - The number of dentists in Japan may be too high. The ratio of
      dentists/population, in China, Indonesia, Thailand, and Malaysia, is less than 1
      dentist for every 10,000 people. From this data, it can be seen that there is a
      shortage of dentists in China, Indonesia, Thailand, and Malaysia. The shortage of
      pediatric dentists in these Asian countries is serious, particularly in the
      Philippines where the number of children with dental caries is increasing. There
      is an urgent need to increase the number of pediatric dentists in these
      countries. However, one problem is that dental schools in the Philippines and
      Singapore, do not have a department of pediatric dentistry.

PMID- 10204451
TI  - Reattachment of a subgingivally fractured central incisor tooth fragment: report
      of a case.
AB  - A case report of a 9-year-old boy with a fractured maxillary right incisor and
      ulcerated pulp at the fracture line is presented. On satisfactory completion of a
      root canal filling one week later, the access cavity was restored with glass
      ionomer cement. The fragment was reattached by a light activated hybrid composite
      during the flap surgery. Tetracycline hydrochloride was applied on open root
      surface for a better healing.

PMID- 10204452
TI  - Hypocalcification type amelogenesis imperfecta in permanent dentition in
      association with heavily worn primary teeth, gingival hyperplasia, hypodontia and
      impacted teeth.
AB  - A female patient with hypocalcification type amelogenesis imperfecta in permanent
      dentition in association with heavily worn primary teeth, gingival hyperplasia,
      hypodontia and impacted teeth is presented.

PMID- 10204454
TI  - Class II composite marginal ridge failure: conventional vs. proximal box only
      preparation.
AB  - This study evaluated the force necessary to cause failure at the marginal ridge
      of teeth prepared with conventional class II cavity design and teeth prepared
      with proximal box-only or vertical slot preparation. The teeth were restored with
      Herculite XR or Tetric Ceram. Mean failure loads were not found to be
      statistically significant between conventional class II preparations and proximal
      box-only preparations. The teeth restored with Tetric Ceram were significantly
      more resistant to the vertical load than teeth restored with Herculite.

PMID- 10204453
TI  - The marginal seal of Class II restorations: flowable composite resin compared to
      injectable glass ionomer.
AB  - The objective of this study was to investigate the effect of a flowable composite
      resin (Tetric Flow) versus an injectable glass ionomer (Fuji II LC) on
      microleakage at the cavosurface margin of the proximal box of Class II
      restorations in permanent teeth in-vitro. Thirty caries and restoration-free
      human bicuspids were prepared with mesial and distal slot preparations and were
      filled either with a bonding agent (Optibond) plus a flowable composite resin
      (Tetric Flow), Group I; bonding agent (Optibond) plus a flowable glass ionomer
      (Fuji II LC), Group II; or a flowable glass ionomer (Fuji II LC) with no bonding
      agent, Group III. All specimens were then immersed in a 2% solution of basic
      fuschin dye for 24 hours to allow for dye penetration into possible existing
      gaps. These teeth were then carefully sectioned mesially/distally into two pieces
      using an Isomet saw. The teeth were then studied under a binocular microscope to
      measure depths of dye penetrations as an indication of marginal microleakage at
      the gingival cavosurface margin and scored as follows: 0 = no dye penetration, 1
      = dye penetration into enamel only, 2 = dye penetration into enamel and dentin, 3
      = dye penetration into the pulp. The specimens were also evaluated using a SEM.
      The results showed that there were statistically significant differences between
      Groups I (Tetric Flow) and (Fuji II LC plus bonding agent), II in favor of Group
      I; between Groups I and (Fuji II LC with no bonding agent), III in favor of Group
      I; as well as Groups II and III in favor of Group II (Fuji II LC plus bonding
      agent). Group I (bonding agent plus flowable composite resin) showed
      significantly less microleakage. Group II (bonding agent plus flowable glass
      ionomer) demonstrated a bond that existed between the bonding agent and the glass
      ionomer but microleakage within microgaps of the glass ionomer itself Group III
      (flowable glass ionomer plus no bonding agent) demonstrated significant
      microleakage between the glass ionomer and tooth structure, microgaps within the
      glass ionomer, and lack of retention of the restoration. It appears that the use
      of a flowable composite resin (Tetric Flow) plus a bonding agent (Optibond) in
      the proximal box of a Class II restoration in permanent teeth will significantly
      reduce the microleakage at the cavosurface margin when compared with an
      injectable glass ionomer (Fuji II LC) with or without a bonding agent (Optibond).

PMID- 10204455
TI  - The clinical significance of beta hemolytic streptococci of the milleri group in
      oral abscesses.
AB  - Aspirated exudate from 50 patients with oral abscesses were cultured and
      bacterial growth was assessed qualitatively and semi-quantitatively. Bacteria
      were recovered from all specimens. The mean number of species isolated per
      specimen was 3.6 Both facultative and obligate anaerobes were isolated from 39
      (78%) specimens. The most commonly isolated facultative anaerobic species was
      Streptococcus virdans group, while pigmented gram negative bacilli were the most
      commonly isolated obligate anaerobes. Beta-hemolytic Streptococci of the
      "milleri" groups were recovered from 11 (22%) of the abscesses. Eight of those
      isolates were determined to carry Lancefield group F antigen, 2 group C, and 1
      isolate was not groupable for any Lancefield antigen. These abscesses may be
      sequelae of oral infectious disease or trauma. Patients with oral abscesses
      infected with beta hemolytic Streptococci are apt to be male, and less than 35
      years old. They are also likely to have a more rapid onset of infection and to
      require hospitalization for intensive treatment of a life threatening condition.

PMID- 10204456
TI  - Inverted impaction of a mesiodens: a case report.
AB  - Dental, radiological, dermatoglyphic and genetic findings of a patient showing
      inverted impaction of a mesiodens are presented. It is probable that the
      inversion of the mesiodens was caused by contact of the incisal edge of the crown
      of the mesiodens by the apex of the root of the erupting right maxillary central
      incisor tooth.

PMID- 10204457
TI  - Delayed eruption of maxillary primary cuspid associated with compound odontoma.
AB  - Impaction of primary teeth is very rare especially in the maxillary anterior
      teeth. A four-year-old male child with the complaint of delayed eruption of right
      maxillary primary cuspid due to the presence of odontoma is presented.

PMID- 10204458
TI  - Taurodontism in association with supernumerary teeth.
AB  - The dental, radiological, genetic and dermatoglyphic findings of an additional
      patient with taurodontism in association with supernumerary teeth were presented
      and the findings of the patient were compared with those in the literature.

PMID- 10204459
TI  - Dental and craniofacial features of Aarskog syndrome: report of a case and review
      of literature.
AB  - Aarskog syndrome is a rare syndrome with a typical triad of facial, digital and
      genital characteristics. The characteristic cephalometric finding in this patient
      was the unusually large upward slant of SN plane and a steep Ba-N plane. Though
      the patient presented with a class I skeletal pattern, both the maxilla and
      mandible were hypoplastic and retruded with respect to the cranial base. Other
      characteristic features regarding the mandibular morphology were a large FMA (37
      degrees) and Sn-GoGn (44 degrees) angles, a large gonial angle (138 degrees), an
      increase in total anterior facial and lower anterior facial height.

PMID- 10204460
TI  - Bruxism in Rett syndrome: a case report.
AB  - Rett syndrome is a unique and puzzling disorder noted in females and is possibly
      caused by fundamental failures in critical brain connectivity during early
      infancy. The most frequent habits in Rett syndrome are hand sucking or biting,
      bruxism and mouth breathing. Children with musculoskeletal disorders and children
      who suffer from mental retardation commonly grind their teeth. A five year old
      female case with Rett syndrome is presented with significant bruxism in this
      article.

PMID- 10204461
TI  - The effect of guided tissue regeneration on the healing of osseous defects in rat
      calvaria.
AB  - The effect of guided tissue regeneration procedures on the healing of osseous
      defects was studied in Sprague-Dawley rats. A full thickness flap was reflected
      and two 5 mm defects were made in the calvaria of 17 rats. A resorbable membrane
      was placed over one defect in each animal, while the remaining defect served as a
      control. After 3, 5, or 7 wk, healing of the osseous defects was evaluated
      histologically. There was no statistical difference in bone regeneration between
      experimental and control sites at any time period.

PMID- 10204462
TI  - Removal efficiency of calcium hydroxide dressing from the root canal.
AB  - The aim of this study was to investigate whether differences in the composition
      of calcium hydroxide (Ca(OH)2) preparations influence the removal efficiency of
      irrigation solutions used in combination with filing of the canal. Three Ca(OH)2
      preparations were used: Calxyl, Pulpdent paste, and chemically pure Ca(OH)2 mixed
      with distilled water. Fifty-one single-rooted extracted human teeth were prepared
      with a step-back technique and divided into groups A, B, and C. In each group, 15
      teeth were assigned to each Ca(OH)2 preparation while the remaining two served as
      positive and negative controls. Each group of treated teeth was divided into
      three subgroups of five teeth each: subgroup I--canals were irrigated with
      saline, filed with a #25 file, and finally flushed with saline; subgroup II-
      canals were irrigated with NaOCl, filed with a #25 file, and finally flushed with
      NaOCl; and subgroup III--canals were irrigated with NaOCl, filed with a #25 file,
      and finally flushed with tetrasodium EDTA. Canal sections were then photographed,
      and the percentage ratios of Ca(OH)2 coated area to the total canal surface area
      were calculated by image processing analysis. Results revealed: (a) none of the
      methods efficiently removed all dressing from the walls, and (b) concentration of
      the paste used had little effect on the efficacy of the methods applied for the
      removal of the dressing. Excipients (i.e. methylcellulose contained in Pulpdent)
      possibly effect retention of Ca(OH)2.

PMID- 10204463
TI  - In vitro cytotoxicity of one-step dentin bonding systems.
AB  - The cytotoxicity of resinous monomers may vary on mixing, calling into question
      the cytotoxicity of the new dentin bonding agents that are mixed in a single
      vial. The cytotoxicity of fourth and fifth generation dentin bonding agents was
      compared in vitro. All-Bond 2, One-Step, Scotchbond Multi-Purpose, Scotchbond
      One, Syntac, Syntac Single Component, Tenure, and Tenure Quick were tested
      uncured. The cytotoxicity of several dilutions of fourth generation dentin
      primer, dentin bonding agent, dentin primer + dentin bonding agent, and fifth
      generation single component products diluted at 10(-1) to 10(-8) in culture
      medium was recorded with a MTT assay on L929 fibroblasts. Only one synergistic
      (increased cytotoxicity after mixing primer and bonding agent) cytotoxic effect
      was observed with Tenure at 10(-5) dilution. An antagonistic effect (decreased
      cytotoxicity after mixing primer and bonding agent) was observed with All-Bond 2
      between 10(-4) and 10(-8) dilutions. Scotchbond and Syntac fifth generation
      dentin bonding agents were less cytotoxic than their fourth generation
      counterparts. All-Bond and Tenure fifth generation dentin bonding agents were
      more cytotoxic than their fourth generation counterparts only in low dilutions.
      Clinical studies should confirm these good results, because no dramatic
      synergistic cytotoxic effect could be detected.

PMID- 10204464
TI  - Effect of calcium hydroxide and four irrigation regimens on instrumented and
      uninstrumented canal wall topography.
AB  - The topography of instrumented and uninstrumented canal walls exposed to calcium
      hydroxide and four different irrigation regimens was observed by scanning
      electron microscopy. After chemomechanical debridement, one tooth in each matched
      pair was medicated with calcium hydroxide. One week later, the teeth were
      irrigated and split longitudinally for evaluation. When no calcium hydroxide was
      used, predentin and pulpal debris covered the dentinal tubules of the
      uninstrumented surfaces in specimens irrigated with water or EDTA, but was absent
      on uninstrumented surfaces in specimens irrigated with NaOCl or NaOCl and EDTA. A
      typical smear layer was absent in instrumented specimens irrigated with NaOCl and
      EDTA, but covered the dentinal tubules of the instrumented surfaces of the EDTA
      irrigated specimens (partially) and the water or NaOCl irrigated specimens
      (completely). Calcospherites or their remnants were seen on the uninstrumented
      canal walls of specimens irrigated with NaOCl or NaOCl and EDTA, respectively.
      Calcium hydroxide use did not alter the surface topography in specimens irrigated
      with water, EDTA, or NaOCl, but seemed to erode the intertubular dentin in
      specimens irrigated with NaOCl and EDTA. All irrigants seemed to effectively
      remove most of the calcium hydroxide.

PMID- 10204465
TI  - Load and strain during lateral condensation and vertical root fracture.
AB  - Vertical loads and root surface strains in extracted teeth during lateral
      condensation using finger and hand spreaders were measured and compared with
      loads and strains at fracture. Six groups each of 10 teeth were tested: maxillary
      central incisor, premolar and molar; and mandibular incisor, premolar and molar.
      Root strains were measured using strain gauges mounted on the apical and middle
      third of the buccal root surface. Statistical analysis was performed at the 95%
      level of confidence. The maximum loads and strains generated by finger spreaders
      were significantly lower than those generated using a hand spreader (D11T). These
      loads and strains were also significantly lower than the values at fracture. Most
      fracture lines were in a buccolingual direction, but maxillary premolars with two
      separate roots and the mesiobuccal root of maxillary molars showed more variation
      in fracture site. The results suggest that lateral condensation alone should not
      be a direct cause of vertical root fracture. The use of finger spreaders,
      however, is associated with lower risk.

PMID- 10204466
TI  - An evaluation of the CO2 laser for endodontic disinfection.
AB  - The goal of this study was to evaluate the bactericidal action of the CO2 laser
      on animal teeth infected with an endodontic bacterial species. After
      instrumentation, 24 freshly extracted incisors were inoculated with a known
      concentration of Actinomyces odontolyticus and incubated anaerobically for 18 h.
      The incisors were separated into three groups: group 1--untreated control teeth;
      group 2--teeth treated with 3% NaOCl; and group 3--teeth lased with a CO2 laser
      at 5 W using three successive 9.9 s irradiation periods with 10 s between
      treatments. For each of the three groups, 60 microliters samples were removed
      using gel loading capillary pipette tips, and the diluted samples were plated in
      triplicate on Columbia agar plates. After a 5- to 6-day incubation, the colony
      forming units were counted, and the quantitative results were subjected to an
      analysis of variance. The results of this analysis indicated an average 85%
      decrease in the colony-forming units in the laser-treated group, compared with
      the control group. According to Fisher and Scheffe tests, the differences in the
      averages between the control and laser groups were statistically significant (p <
      0.05). The NaOCl treatment was statistically superior to the CO2 laser treatment.

PMID- 10204467
TI  - Genotoxicity and cytotoxicity of the epoxy resin-based root canal sealer AH plus.
AB  - Previous studies with four rapid in vitro and in vivo test systems have shown
      that the epoxy resin-based root canal sealer AH26 may be genotoxic and cytotoxic
      (9). The purpose of this study was to determine the cytotoxic and genotoxic
      effects of the new resinous root canal sealer AH Plus by means of the growth
      inhibition test with primary human periodontal ligament fibroblasts and permanent
      3T3 monolayers, the procaryotic umu test, the eucaryotic DNA synthesis inhibition
      test, and the in vivo alkaline filter elution test. In addition, Ames tests were
      performed with extracts from AH Plus. AH Plus caused only slight or no cellular
      injuries. Furthermore, no genotoxicity and mutagenicity were revealed by AH Plus.
      These data should be taken into consideration when deciding about a root canal
      sealer.

PMID- 10204468
TI  - Effect of dentin bonding agents on the secretion of inflammatory mediators from
      macrophages.
AB  - Dentin bonding agents (DBAs) have been proposed as substitutes for amalgam as
      root-end filling materials. The current study tested the hypothesis that certain
      components of DBAs could alter the secretion of cytokines from macrophages. Such
      alteration would likely be undesirable for healing of the periapical tissues.
      Human THP-1 macrophages were exposed to 2-hydroxyethyl methacrylate, 4
      methacryloxyethyl trimelliate anhydride, bisphenol-gycidylmethacrylate, and
      urethane dimethacrylate. The secretion of interleukin-1 beta (IL-1 beta) and
      tumor necrosis factor-alpha (TNF-alpha) were measured with or without challenge
      by lipopolysaccharide (LPS). Results showed that all DBA components completely
      suppressed LPS-induced IL-1 beta and TNF-alpha secretion at concentrations that
      suppressed mitochondrial activity by 50%. In addition, 4-methacryloxyethyl
      trimelliate anhydride induced secretion of IL-1 beta, but not TNF-alpha, without
      the LPS challenge. These results indicate that DBA components may alter normal
      macrophage-directed inflammatory responses if the macrophages are exposed to
      sufficiently high concentrations of these components.

PMID- 10204469
TI  - Thrombin activates the growth, cell-cycle kinetics, and clustering of human
      dental pulp cells.
AB  - Thrombin is activated during vascular injury and inflammation of the dental pulp.
      In the present study, we found that thrombin can stimulate the proliferation of
      pulp cells in a dose-dependent manner as analyzed by modified MTT assay. The cell
      number increased by 1.6, 1.77, and 2.14-fold over that of control after exposure
      to 5, 10, and 20 units/ml of thrombin for 5 days. Flow cytometry studies also
      found that thrombin (10 units/ml) can induce the cell cycle progression of pulp
      cells after 24 h of incubation, as revealed by increasing the proportion of cells
      in the S phase and the G2/M phase from 29 to 72%. Moreover, exposure to thrombin
      (> 5 units/ml) for 3 days led to marked clustering of pulp cells. We concluded
      that thrombin can regulate the growth, cell cycle progression, and functional
      reorganization of the pulp tissue during pulp healing and inflammatory processes.

PMID- 10204470
TI  - Long-term evaluation of the influence of smear layer removal on the sealing
      ability of different sealers.
AB  - The purpose of this study was to examine the effect of the smear layer on apical
      microleakage over 16 wk. One hundred and four extracted human teeth were assigned
      to four groups treated as follows: group A1--smear layer was left intact and
      canals were obturated with gutta-percha and Roth 811; group A2--smear layer was
      left intact and canals were obturated with gutta-percha and AH26; group B1--smear
      layer was removed and canals were obturated with gutta-percha and Roth 811; and
      group B2--smear layer was removed and canals were obturated with gutta-percha and
      AH26. Microleakage was measured by the electrochemical method. In parallel, 12
      teeth were examined under a scanning electron microscope. The results indicated
      that the smear layer removal resulted in a statistically significant reduction of
      microleakage values in groups obturated with AH26. The presence or absence of
      smear layer had no significant effect on the sealing ability of Roth 811.

PMID- 10204471
TI  - Torsional strength of Gates Glidden drills exposed to clinical conditions.
AB  - Gates Glidden drills are exposed to a variety of conditions during clinical
      usage. These usually include canal preparation, endodontic irrigants, and
      sterilization procedures. All sizes 1 to 6 (n = 5/size) were tested and the
      torsional fracture strength determined. There were four groups (n = 30/group):
      group A, control; group B, sterilized 10 times; group C, exposed to 5.25% NaOCl
      during testing; and group D, sterilized 10 times and exposed to NaOCl during
      testing. Data were analyzed by ANOVA. Tukey-Kramer intervals at the 0.05
      significance level were calculated. No significant differences were noted as a
      result of simulated clinical conditions. The larger diameter instruments had
      significantly higher torsional fracture strength.

PMID- 10204472
TI  - Radiographic appearance of titanium posts in endodontically treated teeth.
AB  - Titanium and titanium alloy posts are currently being used in complex dental
      restorations. Titanium posts have been shown to be less radiopaque than stainless
      steel and to have a radiographic density similar to gutta-percha. This
      radiographic similarity can make detection of a titanium post difficult. Failure
      to identify the presence of a titanium post before the initiation of retreatment
      could cause significant complications for the treating endodontist. Five cases
      are presented to describe the radiographic subtleties that can be used to detect
      the presence of a titanium post.

PMID- 10204473
TI  - An endoscopic technique for endodontic surgery.
AB  - Modern endoscopy has been in existence for > 100 yr. As the desire for increased
      visualization in endodontic surgery continues, there is a constant search for
      better instruments and techniques to meet this demand. Endoscopy provides the
      surgeon with outstanding vision and ease of use. This study refines the
      endoscopic technique for endodontic surgery.

PMID- 10204474
TI  - Unusual horizontal and vertical root fractures of maxillary molars: an 11-year
      follow-up.
AB  - Intra-alveolar root fractures of posterior teeth are rare when compared with
      other dental injuries. This case report describes one vertical and two horizontal
      root fractures of teeth 3, 14, and 15. The teeth all tested normal to cold and
      electric pulp tests. The patient reported no history of accidental trauma, and no
      signs of scarring were found. These fractures were discovered during a routine
      full-mouth radiographic survey. All teeth were asymptomatic and in good function.
      During the 11 yr that followed, there was no dental treatment, except for routine
      periodontal maintenance. The patient had one abscess that occurred after 9 yr on
      tooth 3, which had to be extracted. The upper left molars are surprisingly still
      in function and asymptomatic. Either occlusal or lateral trauma may be the cause
      of these fractures. This would strongly suggest night guard appliances for
      patients who clench or grind. A psychological evaluation of the patient might
      reveal neurosis, anxiety, or stress situations affecting teeth.

PMID- 10204475
TI  - Current status of a mucosal vaccine against dental caries.
AB  - The evidence of a specific bacterial cause of dental caries and of the function
      of the salivary glands as an effector site of the mucosal immune system has
      provided a scientific basis for the development of a vaccine against this highly
      prevalent and costly oral disease. Research efforts towards developing an
      effective and safe caries vaccine have been facilitated by progress in molecular
      biology, with the cloning and functional characterization of virulence factors
      from mutans streptococci, the principal causative agent of dental caries, and
      advancements in mucosal immunology, including the development of sophisticated
      antigen delivery systems and adjuvants that stimulate the induction of salivary
      immunoglobulin A antibody responses. Cell-surface fibrillar proteins, which
      mediate adherence to the salivary pellicle, and glucosyltransferase enzymes,
      which synthesize adhesive glucans and allow microbial accumulation, are virulence
      components of mutans streptococci, and primary candidates for a human caries
      vaccine. Infants, representing the primary target population for a caries
      vaccine, become mucosally immunocompetent and secrete salivary immunoglobulin A
      antibodies during the first weeks after birth, whereas mutans streptococci
      colonize the tooth surfaces at a discrete time period that extends around 26
      months of life. Therefore, immunization when infants are about one year old may
      establish effective immunity against an ensuing colonization attempts by mutans
      streptococci. The present review critically evaluates recent progress in this
      field of dental research and attempts to stress the protective potential as well
      as limitations of caries immunization.

PMID- 10204476
TI  - Simultaneous induction of specific immunoglobulin A--producing cells in major and
      minor salivary glands after tonsillar application of antigen in rabbits.
AB  - The immunoglobulin A (IgA)-producing cells in the stroma of major salivary glands
      are induced by antigenic stimulation of the mucosal immune system. Whether such
      cells also are induced in minor salivary glands by this stimulation remains to be
      determined. After application of sheep red blood cells to the palatine tonsils
      every 3 days for 6 weeks, anti-sheep red blood cell IgA was detected in saliva
      both by agglutination tests and by enzyme-linked immunosorbent assay. Using
      enzyme-linked immunospot assay, an increase in the number of anti-sheep red blood
      cell IgA-producing cells was found in minor as well as in major salivary glands
      of the sixth week of application; such cells constituted 4.9% to 5.9% of the
      total number of IgA-producing cells in these tissues. Tonsillar application of
      whole cells of formalin-killed Streptococcus sobrinus induced anti-S. sobrinus
      IgA in saliva. The number of anti-S. sobrinus IgA-producing cells in the above
      glands simultaneously increased over 6 weeks, and reached 5.2-5.6% of the total
      number of IgA-producing cells.

PMID- 10204477
TI  - Effect of inactivation of gtf genes on adherence of Streptococcus downei.
AB  - The activity of glucosyltransferases (GTF), a group of enzymes that synthesize
      water-soluble and -insoluble glucans from sucrose, significantly contributes to
      the cariogenicity of mutans streptococci. Streptococcus downei produces four
      glucosyltransferases, GTFI, which produces insoluble glucan, and GTFS, GTFT, and
      GTFU, which synthesize soluble glucans. We have previously reported that
      inactivation of gtfS results in altered adherence and have now examined its
      interaction with other enzymes by constructing mutants which were gtfS,
      gtfS/gtfT, gtfS/gtfI and gtfI. The mutants were tested for their ability to
      accumulate on wires and on plastic microtiter trays in the presence of sucrose.
      The gtfS mutant displayed a reduced ability to adhere compared to the wild type
      but there was no further reduction of adherence in a gtfS/gtfT mutant. In
      contrast, the gtfS/gtfI double mutant showed a drastic reduction in adherence and
      when gtfI alone was inactivated, bacteria were unable to adhere to a hard
      surface. The results confirmed that insoluble glucan is required for strong
      adherence to a smooth surface but that the amount and structure of this glucan is
      dependent upon the availability of soluble glucans to act as primer molecules.

PMID- 10204478
TI  - Identification of oral mitis group streptococci by arbitrarily primed polymerase
      chain reaction.
AB  - "Mitis group" streptococci are commensal but may play some role in dental caries,
      septicemia or endocarditis. Rapid genotypic identification would aid studies of
      dental plaque ecology, or diagnostic use. AP-PCR with 58 unpaired arbitrary
      primers was used to characterize 7 Streptococcus gordonii, 11 Streptococcus
      sanguis, 2 Streptococcus crista, 5 Streptococcus parasanguis, 18 Streptococcus
      oralis, and 36 Streptococcus mitis (22 biovar 1 and 14 biovar 2). S. parasanguis
      16S rRNA variable region primer RR2 produced species-specific bands with all S.
      gordonii and S. sanguis. Human V beta 1 T-cell receptor primer 434 yielded
      concordant genotypic identification of all phenotypically defined S. crista and
      S. parasanguis, 83% of S. oralis, and 74% of S. mitis biovar 1. Amplicon patterns
      for S. mitis biovar 2 were heterogeneous. Findings suggest that primers RR2 and
      434 in succession will allow rapid identification of genotypic groups
      corresponding closely to mitis group species established by phenotype.

PMID- 10204479
TI  - Acid-induced acid tolerance and acidogenicity of non-mutans streptococci.
AB  - Acid tolerance and acidogenicity of non-mutans streptococci and their capacity of
      acid adaptation were studied. The cells of non-mutans streptococci (Streptococcus
      sanguis [Streptococcus sanguinis], Streptococcus gordonii, Streptococcus oralis
      and Streptococcus mitis) grown at pH 7.0 showed 0.0088% to 71% viability after
      acidification at pH 4.0 for 60 min, whereas the cells of mutans streptococci
      (Streptococcus mutans) were not killed by the acidification. Washed cells of non
      mutans streptococci lowered pH to 4.04-4.33 in the presence of glucose, while
      mutans streptococci cells lowered pH to 3.70. When the growth pH was shifted to
      5.5 for 30-90 min, the viability of non-mutans streptococci after the
      acidification at pH 4.0 for 60 min increased (0.25% to 91%) and the minimum pH
      values of the cells in the presence of glucose decreased (3.90 4.19). Along with
      the increase in acid tolerance and acidogenicity, non-mutans streptococci
      increased activities of H(+)-ATPase and arginine deiminase and amounts of stress
      proteins cross-reacting with 60 kDa and 70 kDa heat shock proteins (Hsp60 and
      Hsp70). These results indicate that non-mutans streptococci were capable of
      increasing their acid tolerance and acidogenicity in response to environmental
      acidification. Furthermore, it is suggested that the acid adaptation observed in
      non-mutans streptococci cells could involve the induction of H(+)-ATPase,
      arginine deiminase and stress protein syntheses. The strains of non-mutans
      streptococci, which are pioneer bacteria for dental plaque formation and
      predominant in plaque microbial flora, may play a significant role in shifting
      the dental plaque environment toward acidic and consequently promoting the
      colonization of more acid-tolerant and acidogenic bacteria such as mutans
      streptococci and lactobacilli.

PMID- 10204480
TI  - Adherence of Peptostreptococcus micros morphotypes to epithelial cells in vitro.
AB  - Peptostreptococcus micros, which is associated with oral and non-oral mixed
      anaerobic infections, occurs in three colony morphotypes, the smooth type, the
      rough type and the smooth variant of the rough type. These types differ in
      surface structures; the rough type expresses large fibrillar surface appendages,
      which are absent on the surface of both the smooth and the smooth variant of the
      rough type. To determine the role of these surface structures in adherence we
      characterized the adherence of the three morphotypes of P. micros to epithelial
      cells in vitro. Although all three types adhered well to epithelial cells,
      adhering numbers of the rough type were significantly lower than those of the
      smooth and the smooth variant of the rough type. Protease treatment increased the
      adherence of the rough type of the level of the two other types. The adherence of
      all three types was reduced more than 85% by treatment with 10 mM sodium
      periodate. Furthermore, the adherence was pH independent and could not be blocked
      by incubation with antisera to the bacteria. In addition, we determined the
      capacity to invade epithelial cells by P. micros. In an acridine orange assay
      such invasion could not be detected. Our results suggest that the adherence of P.
      micros to epithelial cells is mediated by periodate-sensitive extracellular
      polysaccharides and that the protruding fibril-like protein surface structures of
      the rough type have an obstructive effect on the adherence.

PMID- 10204481
TI  - Diversity of oral asaccharolytic Eubacterium species in periodontitis-
      identification of novel phylotypes representing uncultivated taxa.
AB  - Oral asaccharolytic Eubacterium species are associated with periodontal disease
      and other oral infections. The aim of this study was to use a culture-independent
      molecular technique to determine the diversity of asaccharolytic Eubacterium
      species in subgingival plaque in periodontitis. An oligonucleotide PCR primer
      designed to amplify 16S rRNA genes of the oral asaccharolytic Eubacterium branch
      of the phylogenetic tree was constructed. This primer was used together with a
      universal primer in PCRs to amplify gene sequences directly from a single
      subgingival plaque sample. Fifty PCR products were purified by cloning, fully
      sequenced and subjected to molecular phylogenetic analysis. The sequences were
      assigned to four groups within a single lineage of the low G + C gram-positive
      bacteria. Group I (58% of the cloned sequences) was assigned to a branch that
      included Eubacterium nodatum, and Group II (22%) to a branch including
      Eubacterium infirmum. Group III (8%) was distinct from but related to E. infirmum
      at the species level, and Group IV (12%) was another novel taxon more distantly
      related to E. infirmum and E. nodatum.

PMID- 10204482
TI  - Effects of pH on the glucose and lactate metabolisms by the washed cells of
      Actinomyces naeslundii under anaerobic and aerobic conditions.
AB  - Effects of pH on the glucose and lactate metabolism by the washed cells of
      Actinomyces naeslundii genospecies 1 and 2 under anaerobic and aerobic conditions
      were studied. The rate of acid production from glucose was the highest at pH 7.0
      and decreased as the pH lowered to 4.5, irrespective of atmospheric conditions.
      The anaerobic end-product in the absence of bicarbonate was mainly lactate, while
      in the presence of bicarbonate the rate of acid production increased 1.8-2.5
      times with the production of formate, acetate and succinate in addition to
      lactate. Under aerobic conditions, the cells produced acids from glucose along
      with oxygen consumption and the end-product was mainly acetate. In contrast to
      the glucose metabilism, the cells produced base from lactate along with oxygen
      consumption. The rates of base production and oxygen consumption were the highest
      at pH 5.5. The end-products from lactate were acetate and pyruvate. These results
      indicate that oral actinomyces has a various activity of glucose and lactate
      metabolism at a wide range of environmental pH and suggest its flexibility in
      surviving in dental plaque, where the environmental factors fluctuate.

PMID- 10204483
TI  - Oxygen metabolism by Treponema denticola.
AB  - Treponema denticola strains ATCC 35405 and ASLM were found to have moderately
      active oxygen metabolism and consumed some 0.46 mumol O2/h/mg cell protein in
      anaerobic growth medium or about ten times this amount in aerobic medium. There
      appeared to be no differences between the two strains in their oxidative
      metabolism. The spirochetes showed significant endogenous O2 utilization, which
      was stimulated only slightly by added glucose or arginine, moderately by glycine,
      but markedly by casamino acids or brain-heart infusion broth. O2 metabolism by
      intact cells was insensitive to cyanide and so did not appear to involve cyanide
      sensitive cytochrome oxidases. Moreover, difference spectra of cell extracts and
      membranes did not reveal heme profiles. However, the spirochetes did have very
      active reduced nicotinamide adenine dinucleotide (NADH) oxidase(s) and also
      contained the protective enzymes NADH peroxidase and superoxide dismutase. Both
      the oxidase(s) and the peroxidase had rather broad substrate specificities.
      Either NADH or reduced nicotinamide adenine dinucleotide phosphate could serve as
      reductant, and the enzymes were active with a variety of oxidants. Enzyme
      activity in fresh cell extracts was only somewhat stimulated by added flavins,
      but after frozen storage, the activity became much more activated by flavin
      adenine nucleotide, and to a lesser extent, by flavin mononucleotide. The enzymes
      were insensitive to fluoride, which inhibits heme-based but not flavin-based
      oxidases at low pH values. Clearly, these anaerobic spirochetes have significant
      oxygen metabolism, even at the low levels of O2 measured in periodontal pockets
      and contain enzymes that offer at least moderate protection against damage by
      reactive oxygen species.

PMID- 10204484
TI  - A new era for cancer immunotherapy based on the genes that encode cancer
      antigens.

PMID- 10204485
TI  - Negative selection of immature B cells by receptor editing or deletion is
      determined by site of antigen encounter.
AB  - Immature B cells that encounter self-antigen are eliminated from the immune
      repertoire by negative selection. Negative selection has been proposed to take
      place by two distinct mechanisms: deletion by apoptosis or alteration of the
      antigen receptor specificity by receptor editing. While convincing evidence
      exists for each, the two models are inherently contradictory. In this paper, we
      propose a resolution to this contradiction by demonstrating that the site of
      first antigen encounter dictates which mechanism of negative selection is
      utilized. We demonstrate that the bone marrow microenvironment provides signals
      that block antigen-induced deletion and promote RAG reinduction. In the
      periphery, the absence of these signals allows the immature B cell to default to
      apoptosis as a result of BCR engagement.

PMID- 10204486
TI  - Positive selection as a developmental progression initiated by alpha beta TCR
      signals that fix TCR specificity prior to lineage commitment.
AB  - During positive selection, immature thymocytes commit to either the CD4+ or CD8+
      T cell lineage ("commitment") and convert from short-lived thymocytes into long
      lived T cells ("rescue"). By formal precursor-progeny analysis, we now identify
      what is likely to be the initial positive selection step signaled by alpha beta
      TCR, which we have termed "induction". During induction, RAG mRNA expression is
      downregulated, but lineage commitment does not occur. Rather, lineage commitment
      (which depends upon the MHC class specificity of the alpha beta TCR) only occurs
      after downregulation of RAG expression and the consequent fixation of alpha beta
      TCR specificity. We propose that positive selection can be viewed as a sequence
      of increasingly selective developmental steps (induction-->commitment-->rescue)
      that are signaled by alpha beta TCR engagements of intrathymic ligands.

PMID- 10204487
TI  - Control of V(D)J recombinational accessibility of the D beta 1 gene segment at
      the TCR beta locus by a germline promoter.
AB  - The germline promoter region upstream of the D beta 1 gene segment in the murine
      TCR beta locus was deleted to assess its role in controlling V(D)J recombination.
      Associated with diminished D beta 1 region germline transcription, rearrangement
      of the D beta 1 but not the D beta 2 gene segment was reduced 10- to 20-fold. A
      corresponding reduction in RAG-mediated cleavage at the D beta 1 and J beta 1
      signal sequences was apparent only when purified CD4- CD8- thymocytes were
      analyzed because, as we demonstrate, cleavage at these gene segments also
      occurred in CD4+ CD8+ thymocytes. These findings suggest that germline promoters
      regulate localized accessibility of gene segments for recombination and that in
      CD4+ CD8+ thymocytes TCR beta allelic exclusion does not result from
      inaccessibility of D beta gene segments.

PMID- 10204488
TI  - Essential role of LAT in T cell development.
AB  - The linker molecule LAT is a substrate of the tyrosine kinases activated
      following TCR engagement. Phosphorylated LAT binds many critical signaling
      molecules. The central role of this molecule in TCR-mediated signaling has been
      demonstrated by experiments in a LAT-deficient cell line. To probe the role of
      LAT in T cell development, the LAT gene was disrupted by targeting. LAT-deficient
      mice appeared healthy. Flow cytometric analysis revealed normal B cell
      populations but the absence of any mature peripheral T cells. Intrathymic
      development was blocked within the CD4- CD8- stage. No gross abnormality of NK or
      platelet function was observed. LAT is thus critical to both T cell activation
      and development.

PMID- 10204489
TI  - Ikaros sets thresholds for T cell activation and regulates chromosome
      propagation.
AB  - T cell activation involves the sustained accumulation of T cell receptor (TCR)
      and IL-2 receptor (IL-2R) mediated signaling events that promote cell cycle entry
      and progression. The Ikaros family of nuclear factors regulate this process by
      providing thresholds overcome by receptor signaling. T cells with reduced levels
      of Ikaros activity require fewer TCR engagement events for activation, exhibit a
      greater proliferative response to IL-2, and are less sensitive to inhibitors of
      TCR and IL-2R signaling. Upon T cell activation, Ikaros proteins localize in a
      higher-order chromatin structure where they colocalize with components of the DNA
      replication machinery. Proliferating T cells with reduced Ikaros activity display
      chromosome abnormalities. We propose that participation of Ikaros in higher-order
      chromatin structures controls cell cycle transitions and restricts DNA
      replication.

PMID- 10204490
TI  - Ikaros DNA-binding proteins direct formation of chromatin remodeling complexes in
      lymphocytes.
AB  - The Ikaros gene family encodes zinc finger DNA-binding proteins essential for
      lineage determination and control of proliferation in the lymphoid system. Here,
      we report that, in the nucleus of a T cell, a major fraction of Ikaros and Aiolos
      proteins associate with the DNA-dependent ATPase Mi-2 and histone deacetylases,
      in a 2 MD complex. This Ikaros-NURD complex is active in chromatin remodeling and
      histone deacetylation. Upon T cell activation, Ikaros recruits Mi-2/HDAC to
      regions of heterochromatin. These studies reveal that Ikaros proteins are capable
      of targeting chromatin remodeling and deacetylation complexes in vivo. We propose
      that the restructuring of chromatin is a key aspect of Ikaros function in
      lymphocyte differentiation.

PMID- 10204491
TI  - TCR binding to peptide-MHC stabilizes a flexible recognition interface.
AB  - The binding of TCRs to their peptide-MHC ligands is characterized by a low
      affinity, slow kinetics, and a high degree of cross-reactivity. Here, we report
      the results of a kinetic and thermodynamic analysis of two TCRs binding to their
      peptide-MHC ligands, which reveal two striking features. First, significant
      activation energy barriers must be overcome during both association and
      dissociation, suggesting that conformational adjustments are required. Second,
      the low affinity of binding is a consequence of highly unfavorable entropic
      effects, indicative of a substantial reduction in disorder upon binding. This is
      evidence that the TCR and/or peptide-MHC have flexible binding surfaces that are
      stabilized upon binding. Such conformational flexibility, which may also be a
      feature of primary antibodies, is likely to contribute to cross-reactivity in
      antigen recognition.

PMID- 10204492
TI  - Divergent changes in the sensitivity of maturing T cells to structurally related
      ligands underlies formation of a useful T cell repertoire.
AB  - CD4+ CD8+ thymocyte differentiation requires TCR signaling induced by self
      peptide/MHC ligands. Nevertheless, the resulting mature T cells are not activated
      by these self-complexes, whereas foreign ligands can be potent stimuli. Here, we
      show that the signaling properties of TCR change during thymocyte maturation,
      differentially affecting responses to related peptide/MHC molecule complexes and
      contributing to this discrimination. Weak agonists for CD4+ CD8+ thymocytes lose
      potency during development, accompanied by a change in TCR-associated
      phosphorylation from an agonist to a partial agonist/antagonist pattern. In
      contrast, sensitivity to strong agonists is maintained, along with full
      signaling. This yields a mature T cell pool highly responsive to foreign antigen
      while possessing a wide margin of safety against activation by self-ligands.

PMID- 10204493
TI  - A novel role for the major histocompatibility complex class II transactivator
      CIITA in the repression of IL-4 production.
AB  - Class II transactivator (CIITA) is known as a coactivator for MHC class II gene
      expression in antigen-presenting cells. Surprisingly, when CIITA-/- CD4 T cells
      were stimulated in the presence of IL-12, they produced not only IFNgamma but
      also high levels of IL-4. The IL-4 production is due to the accumulation of IL-4
      gene transcripts in Th1 cells. This transcriptional control is observed in T
      cells differentiating to the Th1 but not Th2 lineage, consistent with induction
      of expression of the CIITA gene in T cells by IFNgamma. Thus, in addition to its
      role in transactivation of genes involved in antigen presentation, CIITA plays a
      critical role during the T cell differentiation by negatively regulating the IL-4
      gene transcription.

PMID- 10204495
TI  - An update on a global shortage of intravenous multivitamins.

PMID- 10204494
TI  - Impaired on/off regulation of TNF biosynthesis in mice lacking TNF AU-rich
      elements: implications for joint and gut-associated immunopathologies.
AB  - We addressed the impact of deleting TNF AU-rich elements (ARE) from the mouse
      genome on the regulation of TNF biosynthesis and the physiology of the host.
      Absence of the ARE affected mechanisms responsible for TNF mRNA destabilization
      and translational repression in hemopoietic and stromal cells. In stimulated
      conditions, TNF ARE were required both for the alleviation and reinforcement of
      message destabilization and translational silencing. Moreover, the mutant mRNA
      was no longer responsive to translational modulation by the p38 and JNK kinases,
      demonstrating that TNF ARE are targets for these signals. Development of two
      specific pathologies in mutant mice, i.e., chronic inflammatory arthritis and
      Crohn's-like inflammatory bowel disease, suggests that defective function of ARE
      may be etiopathogenic for the development of analogous human pathologies.

PMID- 10204496
TI  - Pediatric gastroenterology workforce update.

PMID- 10204497
TI  - Clinical practice guidelines: help or hindrance?

PMID- 10204498
TI  - Intestinal fructose absorption: clinical and molecular aspects.

PMID- 10204499
TI  - Endoscopic diagnosis of lymphoproliferative disease after solid organ
      transplantation.

PMID- 10204500
TI  - Autoimmunity with immunodeficiency: a logical paradox.

PMID- 10204501
TI  - The involvement of the gastrointestinal tract in posttransplant
      lymphoproliferative disease in pediatric liver transplantation.
AB  - BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is a serious
      complication associated with the use of immunosuppression after transplantation.
      In a retrospective study the clinical features of PTLD located primarily in the
      gastrointestinal tract were analyzed. METHODS: Three hundred ninety-two
      consecutive pediatric patients who underwent orthotopic liver transplantation
      (OLT) during a 13-year period with a survival of more than 6 months were
      reviewed. Two immunosuppression protocols were used: cyclosporin A, or tacrolimus
      based primary therapy. Twenty-nine randomly selected liver transplant recipients
      without PTLD were used for comparison of signs and symptoms of gastrointestinal
      PTLD. RESULTS: Among the 30 patients identified with PTLD, 9 had gastrointestinal
      PTLD. The overall incidence density of PTLD was 1.8 per 100 patient-years
      (30/392). Nine patients (30%) had involvement of the gastrointestinal tract,
      whereas 7 (23%) had the gastrointestinal tract as the only involved site. When
      compared with a cohort of liver transplant recipients without PTLD, only
      gastrointestinal bleeding, weight loss, hypoalbuminemia, and protein-losing
      enteropathy were signs most likely associated with gastrointestinal PTLD.
      Hypoalbuminemia was the most sensitive sign of gastrointestinal PTLD. The lower
      tract (ileum and colon) was the most common site of involvement. CONCLUSIONS:
      gastrointestinal involvement is common and occurs in 30% of all patients with
      PTLD. It may be the only affected organ in a subgroup of patients.
      Hypoalbuminemia, gastrointestinal bleeding, and weight loss are features that are
      characteristic of gastrointestinal PTLD. Patients with aggressive
      gastrointestinal signs and symptoms should undergo upper and lower
      gastrointestinal tract endoscopy with biopsy, to establish the diagnosis.

PMID- 10204502
TI  - Increased expression of transforming growth factor-beta1 and thrombospondin-1 in
      congenital hepatic fibrosis: possible role of the hepatic stellate cell.
AB  - BACKGROUND: Congenital hepatic fibrosis is a rare disease characterized by portal
      tract fibrosis and biliary duct ectasia. It is associated with autosomal
      recessive polycystic kidney disease and rarely progresses to cirrhosis. The
      activated stellate cell has been implicated in the pathogenesis of alcohol- or
      inflammation-mediated cirrhosis through fibrogenic proteins such as transforming
      growth factor-beta1; however, the role of the stellate cell in pure,
      noninflammatory fibrosis is unknown. It has been hypothesized that fibrosis in
      congenital hepatic fibrosis may be caused by upregulation of transforming growth
      factor-beta1 and thrombospondin-1, and that the hepatic stellate cell may be the
      mediator of these proteins. METHODS: Human liver tissue samples from patients
      with congenital hepatic fibrosis (n = 9) and from normal patients (n = 3) were
      analyzed. Tissue homogenates from both groups were analyzed for transforming
      growth factor-beta1 protein and mRNA by Western blot analysis and in situ
      hybridization, respectively. Immunolocalization studies were performed in fixed
      tissue sections from both groups. Stellate cells were cultured from livers
      exhibiting congenital hepatic fibrosis and confirmed by desmin staining. The
      cells were cultured in serum-free medium for 48 hours, and media were collected
      and analyzed by Western blot analysis for thrombospondin-1 and transforming
      growth factor-beta1. RESULTS: Congenital hepatic fibrosis liver tissue
      homogenates had higher levels of thrombospondin-1 and transforming growth factor
      beta1 protein than in normal livers. In congenital hepatic fibrosis tissue,
      transforming growth factor-beta1 was more highly expressed in the ectatic biliary
      epithelium and the perisinusoidal space, whereas thrombospondin-1 localized most
      intensely to the hepatocytes and spared the bile ducts. Congenital hepatic
      fibrosis-derived stellate cells secreted both thrombospondin-1 and transforming
      growth factor-beta1, in vitro. CONCLUSIONS: Transforming growth factor-beta1 and
      thrombospondin-1 may play a role in the pathogenesis of liver fibrosis in
      patients with congenital hepatic fibrosis. One potential source of these
      fibrogenic proteins is the hepatic stellate cell.

PMID- 10204503
TI  - Autoimmune enteropathy with distinct mucosal features in T-cell activation
      deficiency: the contribution of T cells to the mucosal lesion.
AB  - BACKGROUND: Autoimmune enteropathy is normally characterised by crypt
      hyperplastic villous atrophy with enterocyte autoantibodies, activation of
      mucosal lymphocytes and increased epithelial HLA-DR. This case involved a
      severely affected Portuguese infant who was found to have lymphocyte activation
      deficiency and demonstrated correspondingly distinct mucosal features. METHODS: A
      female infant of nonconsanguineous parents was treated for vomiting and
      diarrhoea, first with milk exclusion and then with parenteral nutrition.
      Lymphocyte subsets and immunoglobulin concentrations were normal, but in vitro
      testing showed no activation in response to phytohaemagglutinin, Candida, or
      purified protein derivative, although the response to interleukin (IL)-2 was
      intact. Interleukin-2 deficiency was excluded. Analysis of jejunal biopsy
      specimens revealed only mild villous blunting with absent goblet cells, normal
      epithelial proliferation, and no crypt hyperplasia. The dense infiltrate of CD8+
      and CD4+ T lymphocytes showed normal CD2 and CD3 expression but no activation or
      proliferation markers. HLA-DR was not increased on epithelium or lymphocytes.
      Thus, in addition to in vitro evidence for lymphocyte activation deficiency, the
      mucosal specimens showed no evidence of in situ T-cell activation. RESULTS: After
      development of overwhelming septicaemia, the patient died at 18 months, just
      before a planned bone marrow transplant. CONCLUSIONS: These findings confirm
      significant heterogeneity within autoimmune enteropathy. Formal immune function
      testing should be performed in all affected infants to identify T-cell activation
      deficiencies. The distinct mucosal findings suggest that activated T cells
      usually induce the crypt hyperplastic villous atrophy characteristic of classic
      autoimmune enteropathy.

PMID- 10204504
TI  - No evidence of hepatitis G virus in fulminant hepatic failure in children.
AB  - BACKGROUND: The cause of fulminant hepatic failure in children remains unknown,
      but a viral origin has been suspected in most cases. The recently discovered
      blood-borne virus, hepatitis G, has been suggested as a possible causative agent.
      METHOD: Six consecutive children who underwent liver transplantation for
      fulminant hepatic failure were studied. The children were tested for hepatitis G
      virus antibodies and hepatitis G virus RNA by polymerase chain reaction after
      excluding other causes of fulminant hepatic failure. RESULTS: No evidence of
      hepatitis G virus infection was found in these patients. CONCLUSION: Hepatitis G
      virus is unlikely to be a common cause of fulminant hepatic failure in pediatric
      patients from the upper midwestern United States.

PMID- 10204505
TI  - Growth hormone and insulin-like growth factor-I therapy promote protein
      deposition and growth in dexamethasone-treated piglets.
AB  - BACKGROUND: Dexamethasone treatment facilitates the weaning of premature infants
      from mechanical ventilation but impairs protein homeostasis, lean tissue
      deposition, and growth. The current study was conducted to investigate whether
      dexamethasone mediates these effects by reducing protein synthesis or elevating
      protein breakdown, and whether adjuvant growth hormone+/-insulin-like growth
      factor-I therapy can attenuate such effects. METHODS: Piglets (n = 24) were
      randomized to placebo, a tapered course of dexamethasone (0.5, 0.3, 0.2 mg/kg per
      day for 5, 5 and 4 days each, respectively), dexamethasone + growth hormone 0.1
      mg/kg per day, or dexamethasone + growth hormone + insulin-like growth factor-I
      0.1 mg/kg per day for 14 days. On day 13, 15N-glycine was administered as a
      single oral dose, and urine was collected at timed intervals during the
      subsequent 48 hours. RESULTS: Total urinary N and cumulative 15N excretion were
      higher in all dexamethasone groups than in control subjects. Protein synthesis
      was suppressed, whereas protein breakdown was unaltered by dexamethasone.
      Adjunctive growth hormone+/-insulin-like growth factor-I therapy enhanced protein
      synthesis, but only combined therapy improved net protein gain compared with
      dexamethasone alone. Higher circulating insulin-like growth factor-I may have
      mediated the greater net protein gain. Blood urea nitrogen was elevated in all
      dexamethasone-treated groups at days 6 and 11 but was normalized by day 15 with
      adjunctive growth hormone+/-insulin-like growth factor-I. From a functional
      perspective, both adjunctive growth hormone and growth hormone+/-insulin-like
      growth factor-I partially attenuated the dexamethasone-induced reduction in
      weight and length gain but not in whole body lean and fat mass. CONCLUSION:
      Adjunctive growth hormone+/-insulin-like growth factor-I therapy partially
      reverses the dexamethasone-induced reduction in protein synthesis, resulting in
      improved growth when given concurrently with a low tapering dose of
      dexamethasone.

PMID- 10204506
TI  - Prediction of survival in extrahepatic biliary atresia by hepatic duplex
      sonography.
AB  - BACKGROUND: The clinical course of biliary atresia patients is extremely
      variable. To optimize conservative treatment and correctly schedule liver
      transplantation, noninvasive investigations that are predictive of individual
      survival and that can be performed regularly are needed. In this study, the
      prognostic value of Doppler sonography was investigated in these patients.
      METHODS: Thirty biliary atresia patients (age range, 1 month to 15.2 years; mean,
      4.0 years) and 38 control subjects underwent standardized Doppler sonography of
      liver and spleen. Biochemical tests of liver function and of fibrogenesis were
      performed in parallel. Individual clinical outcome was registered 1 and 2 years
      later. RESULTS: In control subjects, maximum portal flow velocity (Vmax) was more
      than 16 cm/sec, and the hepatic vein flow pattern was triphasic. Among children
      with biliary atresia, those with diminished portal Vmax, a flattened hepatic vein
      flow curve, or a hepatic artery resistance index of 0.8 or more had significantly
      lower indices of hepatic protein synthesis (albumin, cholinesterase), higher
      bilirubin levels, and higher concentrations of markers of connective tissue
      turnover (procollagen peptides, laminin P1) than did those with normal Doppler
      sonography measurements. The rate of survival without transplantation during the
      following 2 years was significantly lower in children with abnormal Doppler
      findings. From portal and hepatic vein flow measurements, patient survival 2
      years later could be predicted with an accuracy of 93%. CONCLUSIONS: In children
      with extrahepatic biliary atresia, Doppler sonography of the hepatic blood flow
      is a noninvasive indicator of disease severity. Moreover, it allows a highly
      accurate prediction of patient survival for the following 2 years.

PMID- 10204507
TI  - Coagulation and fibrinolysis in children, adolescents, and young adults with
      inflammatory bowel disease.
AB  - BACKGROUND: Patients with Crohn's disease and ulcerative colitis have an
      increased risk of thromboembolic events. METHODS: Data were collected from 24
      patients aged 4.5 to 23 years who had inflammatory bowel disease. Platelet count,
      antithrombin, fibrinogen, prothrombin fragment F1+2, soluble thrombomodulin,
      tissue plasminogen activator, D-dimer, and plasminogen activator inhibitor-1
      antigen were investigated. In addition the response to activated protein C, the
      factor V R506Q mutation, protein C, free protein S antigen, and lipoprotein (a)
      were analyzed. These data were compared with medical treatment, duration, and
      disease activity, estimated with the Pediatric Crohn's Disease Activity Index or
      the Clinical Colitis Activity Index. RESULTS: Forty-five percent of our patients
      showed an increase in fibrinogen, 29% in prothrombin fragment F1+2, and 20% in
      platelet count, plasminogen activator inhibitor- antigen, and soluble
      thrombomodulin. Thrombomodulin was higher in active disease than in inactive
      disease and in Crohn's disease than in ulcerative colitis. Fibrinogen was also
      higher with Crohn's disease and tended to be higher in active disease than in
      ulcerative colitis and inactive disease. Plasminogen activator inhibitor-1
      antigen was significantly higher in patients with Crohn's disease than in those
      with ulcerative colitis and was higher in the patient group treated with
      steroids. CONCLUSION: As has been shown in adults, young patients with active and
      inactive inflammatory bowel disease were found to have abnormal coagulation and
      fibrinolysis. The relevance as a thromboembolic risk factor is discussed.

PMID- 10204508
TI  - Gastroesophageal reflux and respiratory phenomena in infants: status of the
      intraluminal impedance technique.
AB  - BACKGROUND: The coincidence of recurrent respiratory symptoms and
      gastroesophageal reflux (GER) is a well-known phenomenon in infants. Twenty-four
      hour pH metry is the presumed gold standard of diagnostic tools for this symptom
      complex, but with this method, only acid (pH <4) and alkaline (pH >7) GER can be
      detected. Gastroesophageal reflux with an esophageal pH in the physiological
      range (pH 5-6.8) may represent many cases of clinically relevant GER unrecognized
      by pH metry. In this study the intraluminal multiple electrical impedance (IMP)
      procedure for complete registration of GER was compared with pH metry for its
      diagnostic value in the presence of respiratory symptoms. METHODS: Twenty-two
      infants with recurrent regurgitation or pulmonary problems were investigated
      simultaneously with IMP, pH metry, and polygraphy during two feeding periods.
      Heart rate, oxygen saturation, sleep states, and oronasal flow were recorded,
      among other parameters. RESULTS: Three hundred sixty-four occurrences of GER were
      detected by IMP; only 11.4% had a pH less than 4 and were therefore recognized by
      pH metry. Three hundred twelve (84.8%) occurrences were associated with breathing
      abnormalities, and 11.9% of these were detected by pH metry. Nineteen instances
      were accompanied by a decrease of oxygen saturation of more than 10% of the
      initial value. Only three (15.8%) of these had a pH less than 4. The remaining 16
      reflux episodes were recognized by IMP only. After software-aided preselection,
      165 instances of apnea were visually validated, 49 of which were accompanied by
      GER. Thirty-eight (77.6%) of these were exclusively recorded by IMP. CONCLUSIONS:
      The use of pH metry alone cannot detect most GER incidents accompanied by
      respiratory symptoms and therefore does not appear to be suitable for this
      approach. The pH-independent IMP technique promises to be a reliable tool for
      presumably GER-associated respiratory symptoms.

PMID- 10204509
TI  - Incidence of dysplasia in pelvic pouches in pediatric patients after ileal pouch
      anal anastomosis for ulcerative colitis.
AB  - BACKGROUND: The purpose of this study was to evaluate the incidence of dysplasia
      and the mucosal adaptation patterns of pelvic pouches in children and adolescents
      who had undergone ileal pouch-anal anastomosis for ulcerative colitis. METHODS:
      Between 1982 and 1996, 176 pediatric patients with ulcerative colitis underwent
      ilial pouch-anal anastomosis. Seventy-six patients were followed up after surgery
      at the Cleveland Clinic. Pouch biopsy specimens were reviewed for dysplasia and
      to determine mucosal adaptation patterns. Fifty-eight of the 76 patients had an
      average of three mucosal biopsies during a mean follow-up of 5 years. Demographic
      and surgical data were abstracted from archives of medical records. All
      previously obtained pouch biopsy specimens were re-evaluated by a single
      pathologist to ensure standardized interpretation. RESULTS: No dysplasia was
      identified in screening specimens of 76 children and adolescents including 5
      patients who showed dysplasia in resected colon specimens. The pattern of mucosal
      adaptation was categorized using previously reported criteria. Type A was defined
      as normal mucosa or mild villous atrophy with no or mild inflammation. Type B
      mucosa showed transient atrophy with temporary moderate inflammation followed by
      normalization of architecture. Type C mucosa was defined as a pattern of
      persistent atrophy with severe inflammation. In the study cohort, the patterns of
      mucosal adaptation, type A (56.9%; n = 33), type B (32.8%; n = 19), and type C
      (10.3%; n = 6), were comparable with those reported in adults. The rate of pouch
      failure and diagnosis of Crohn's disease were similar in each group and were not
      related to the specific adaptation pattern. Most of the patients with type C
      mucosa had clinical symptoms of pouchitis requiring periodic antibiotic therapy.
      No dysplasia was identified in any biopsy specimen reviewed. CONCLUSIONS: Similar
      morphologic changes can be seen in ileal pouches in pediatric and adult patients.
      There seemed to be no increased risk of dysplasia in children and young adults
      who had undergone ilial pouch-anal anastomosis surgery for ulcerative colitis
      during a 5 year follow-up. Because the long-term risk of development of dysplasia
      is unknown, an initial screening should be performed 5 years after the creation
      of a pelvic pouch in children or when the total disease duration exceeds 7 years.
      Once identified, patients with Type C mucosa should have annual screening for
      dysplasia until further data become available.

PMID- 10204510
TI  - Clinical quiz. Mycobacterium avium-intracellurare.

PMID- 10204511
TI  - Congenital hepatic arterioportal fistula in a 3-year-old child.

PMID- 10204512
TI  - Pneumatosis cystoides intestinalis with labial crepitus in an infant with acute
      lymphoblastic leukemia.

PMID- 10204515
TI  - Genetic mutations causing hereditary cholestasis.

PMID- 10204513
TI  - Cystic lymphangioma in an asymptomatic newborn: an uncommon localization in the
      ileum.

PMID- 10204516
TI  - APC gene testing for familial adenomatous polyposis.

PMID- 10204514
TI  - Increased spontaneous chromosomal breakage in Shwachman syndrome.

PMID- 10204517
TI  - Oxygen saturation during esophagogastroduodenoscopy in children: general
      anesthesia versus intravenous sedation.

PMID- 10204518
TI  - Quality of life in inflammatory bowel disease: background and definitions.
AB  - Defining and measuring quality of life is a relatively new dimension of health
      care for many clinicians. The traditional method of evaluating clinical status
      and response to treatment has been to look at disease-specific symptoms, global
      assessments (e.g., impressions of the good, better, or worse condition of a
      patient), days missed at school, and a variety of disease activity scores. These
      impressions and techniques may or may not reflect how patients are functioning
      day to day and how they feel about the illness. To address these issues, health
      related quality of life questionnaires have been developed to measure the
      functional effect of an illness and its treatment on a patient, as perceived by
      the patient. There are four broad domains that are considered part of a health
      related quality-of-life questionnaire: 1) physical and occupational function, 2)
      psychologic state, 3) social interaction, and 4) somatic sensation. In the case
      of children, the perception of parents or caretakers may be added to complete the
      picture. Significant social and psychiatric problems have been described in
      children with IBD, including absenteeism from school, depression, suicide, and
      major disruption of family patterns. To understand fully the impact of
      inflammatory bowel disease and its treatment on patient and family function
      requires one or more quality-of-life instruments that are sensitive to the full
      range of symptoms, growth and development, and response (including side effects)
      to many new therapies.

PMID- 10204519
TI  - The use of focus groups to define patient needs.
AB  - Focus groups are enjoying unprecedented popularity. In this article, the
      advantages and disadvantages of the method are outlined with cautions against the
      uncritical adoption of focus groups designed according to the marketing research
      tradition. It is argued that focus groups require detailed planning, and some
      advice regarding the running of groups, and analysis of data is provided. Special
      attention is directed to the practical and ethical issues in using focus groups
      to define patient needs in the area of childhood inflammatory bowel disease.
      Finally, some suggestions for maximising the full potential of focus groups are
      presented. Focus groups, if used appropriately and judiciously, are an inherently
      flexible method. Ultimately, their use is constrained only by the research
      question and the imagination of the researcher.

PMID- 10204520
TI  - Development and subsequent refinement of the inflammatory bowel disease
      questionnaire: a quality-of-life instrument for adult patients with inflammatory
      bowel disease.
AB  - BACKGROUND: Health-related quality of life (HRQOL) describes the physical,
      social, and emotional attitudes and behavior of people in relation to health
      status. By the 1980s, HRQOL was noted to be impaired in chronic diseases but
      inflammatory bowel disease, had not been extensively described. METHODS: This
      review summarizes the results of several studies describing the development and
      application of a disease-specific HRQOL instrument, the Inflammatory Bowel
      Disease Questionnaire (IBDQ). RESULTS: An initial study described how patients
      with inflammatory bowel disease identified 150 problems they had experienced in
      four domains: bowel, systemic, emotional, and social function. Almost half of
      patients underreported impairment until encouraged by a reminder list. Thirty-two
      questions were included in the final questionnaire and were scored on a 7-point
      scale from I (worst) to 7 (best) for a range of possible scores from 32 to 224.
      Physicians' and spouses' global assessments correlated poorly with patient
      reported HRQOL. Subsequent validation of the IBDQ suggested a strong correlation
      with disease severity (r = -0.5; p < 0.001) and a test-retest reliability of 0.7.
      Mean score changes of 16 to 30 points have been linked to changes in therapy.
      Statistically significant differences also occur between active and inactive
      disease. Results of four clinical trials have included the IBDQ as a measure of
      outcome. A self-administered version and a shortened version of the IBDQ have
      also been validated. CONCLUSIONS: The IBDQ is a valid, reliable, and sensitive
      measure that can be meaningfully applied in clinical trials. The short IBDQ may
      also be useful in clinical research and office practice.

PMID- 10204521
TI  - Inflammatory bowel disease in children and adolescents: mental health and family
      functioning.
AB  - BACKGROUND: Inflammatory bowel disease in children and adolescents often leads to
      an extremely complex somatic and psychiatric situation. The psychological effect
      of inflammatory bowel disease warrants further investigation, especially
      concerning salutogenetic factors that may lead to good mental health despite bad
      somatic conditions. METHODS: These studies used a multimethod design comprising
      both semiquantitative measures, such as rating scales and questionnaires, and
      qualitative in-depth interviews with both the child and his or her parents.
      Clinical comparison groups of matched children with diabetes and chronic tension
      headaches and matched children without chronic physical disease were examined.
      RESULTS: Inflammatory bowel disease often leads to psychiatric sequelae.
      Emotional disorders, especially depression and anxiety symptoms, were found to be
      common. Self-esteem was lowered. A subgroup of children with good mental health
      despite bad somatic conditions was found. They exhibited certain characteristics,
      including good knowledge of the disease, an internal locus of control, a good
      family climate, and an open social network. CONCLUSIONS: This study shows that
      the well-being of a chronically ill child depends not only on the course of the
      physical disease but also on the psychological and social complications that
      often seem to accompany a disease of this kind. The importance of taking good
      care of the psychosocial aspects of inflammatory bowel disease within the
      comprehensive treatment program is discussed.

PMID- 10204522
TI  - Impact of inflammatory bowel disease on educational achievements and work
      prospects.
AB  - Young people with inflammatory bowel disease can hope to achieve educational
      qualifications comparable with those of their peers and to find a supportive
      educational environment to encourage them. In contrast, at work they can expect
      discrimination and lack of support, although such treatment may not be overt.

PMID- 10204523
TI  - Quality of life in children with Crohn's disease: a pilot study.
AB  - BACKGROUND: Focus group meetings were held with two groups, each containing 12
      children with Crohn's disease aged 8 to 12 and 12 to 17 years. The children were
      asked broad questions about how Crohn's disease and its treatment affected their
      lives. To explore these areas in more detail, an 88-item questionnaire was
      developed and read to an additional 16 of 20 children with Crohn's disease
      selected at random from outpatients. At first, many of the children denied that
      Crohn's disease affected their lives at all, but it soon became apparent that
      many were frustrated or angry about physical symptoms, lack of understanding
      about Crohn's disease, unpleasant investigations, treatment, and hospitalisation.
      METHODS: The questionnaire covered six domains of health-related quality of life
      including symptoms and treatment, social, emotional, family, educational, and
      future aspects. RESULTS: Elemental diet was the preferred treatment, although
      surgery was more effective in controlling symptoms. Children receiving steroids
      had more depressive symptoms. Absenteeism from school and inability to engage in
      school sports, swimming, and running were frequent problems. There were also
      difficulties with taking holidays and staying at friends' houses. Worry was
      reported in 14 of 16 children, anger and frustration and feeling fed up in 12 of
      16. CONCLUSIONS: In addition to being a symptomatically disabling condition,
      Crohn's disease has a great impact on the health-related quality of life of
      affected children. Future studies of treatment in children with inflammatory
      bowel disease should include an attempt to assess the impact on the child's
      health-related quality of life.

PMID- 10204524
TI  - Quality of life of parents and siblings of children with inflammatory bowel
      disease.
AB  - BACKGROUND: Few investigators have reported on the quality of life of family
      members of children with inflammatory bowel disease. Psychological symptoms have
      been reported in parents and siblings, but the problems that which give rise to
      these symptoms are seldom examined. In this pilot study, some of the issues that
      affect the quality of life of parents and siblings of children with inflammatory
      bowel disease were examined. METHODS: Focus group meetings were held separately
      with 20 parents and 7 siblings of children with inflammatory bowel disease. The
      participants were encouraged to identify voluntarily problems related to the
      disease that affected their lives, and the discussions were tape recorded. Each
      participant subsequently wrote down the three most important concerns. RESULTS:
      Thirteen (65%) parents were very concerned about the effect of the disease on the
      child's future jobs, marriage, independence) and 11 (55%) were worried about
      problems the ill child was encountering at school. Other issues of most concern
      to parents included side effects of medication (n = 7), limited job prospects (n
      = 3), persistent feelings of guilt (n = 3), and restricted family lifestyle (n =
      1 ). Most siblings (57%) were concerned about their parents' keeping information
      about the illness from them, and three (43%) of them were also concerned about
      others bullying the ill child at school. Other issues of concern to siblings
      included fear about the disease and treatment (n = 3), parents overprotecting the
      ill child, and feelings of jealousy (n = 1). CONCLUSION: Families of children
      with inflammatory bowel disease experience many problems that may affect their
      quality of life. Resources should be made available to help families with these
      concerns.

PMID- 10204525
TI  - Social implications of childhood Crohn's disease.
AB  - BACKGROUND: Children with Crohn's disease may have an impaired quality of life.
      METHODS: A validated questionnaire was mailed to the parents of all child members
      of Crohn's in Childhood Research Association (CICRA) (age range, 5-17 years). It
      investigated aspects of the quality of life of children with Crohn's disease.
      Sixty-four questionnaires were returned together with another 35 from those
      outside the defined age range. Patients in the latter group were not included in
      the analysis. RESULTS: Of the children investigated, 60% had significant absences
      from school, with a mean of 3+/-2.8 months' absence in the previous year. Most
      (53%) thought that their teachers knew nothing about Crohn's disease, and 50%
      thought that teachers were unsympathetic. Of the 24 who had taken examinations
      80% thought they had underachieved because of ill health. Sixty-seven percent of
      children were unable to participate in sports on a regular basis, 60% felt unable
      to leave the house, and 50% were unable to play with their friends. Information
      about Crohn's disease had predominantly come from doctors (89%), information
      booklets (83%), and nursing staff (42%). The commonest questions asked by the
      children were: what is Crohn's disease (50%), why me (64%), will it affect my
      schooling (52%), and will it affect my chances of getting a job (67%).
      CONCLUSION: Children with Crohn's disease have a significantly impaired quality
      of life. They fear everyday childhood activities and fear for their future. These
      children need sympathetic management, and effort should be concentrated on
      improving their day-to-day existence to enable them to lead as normal a life as
      possible.

PMID- 10204526
TI  - Development of a quality-of-life index for pediatric inflammatory bowel disease:
      dealing with differences related to age and IBD type.
AB  - BACKGROUND: A child- and adolescent-generated IBD quality-of-life index was
      designed to be descriptive (to be used to assess the overall impact of IBD on
      individual patients), and evaluative (to be used as an outcome measure in
      clinical trials). METHODS: Item-generation and item-reduction interviews with 82
      patients with IBD aged 8 to 17 years (61 with Crohn's disease, 21 with ulcerative
      colitis; 36 girls, 45 boys) generated a list of ways in which their lives were
      affected by IBD. These issues were incorporated into an item-reduction
      questionnaire, which was administered to 117 patients (87 Crohn's disease, 30
      ulcerative colitis). Patients indicated on a visual analog scale how important an
      item was to them and how often it bothered them. Mean and median importance-plus
      frequency scores for each issue were calculated for the entire group and among
      patients in subgroups according to age and IBD type. RESULTS: Ulcerative colitis
      and Crohn's disease affect the lives of children and adolescents differently.
      Bowel symptoms are more troubling and disabling to patients with ulcerative
      colitis, whereas systemic symptoms and body image concerns are greater for
      patients with Crohn's disease. The impact of Crohn's disease on ability to
      function in school and leisure activities is greater. Worries about future health
      problems and about the effects of IBD on the family are shared. Crohn's disease
      and ulcerative colitis trigger emotional responses of unfairness and frustration,
      but anger and embarrassment are more prevalent in ulcerative colitis. Disparities
      between age groups are fewer and less marked than those between types of IBD.
      CONCLUSION: In selection of items to be retained in a pediatric IBD quality-of
      life measure, the variation in concerns with disease type must be considered. A
      single index to assess IBD-related quality of life must include items of major
      importance to one subgroup of patients, even if not important to all.
      Alternately, a core of common concerns could be supplemented by disease-specific
      modules, thereby increasing the content validity of the tool for all patients.

PMID- 10204527
TI  - Assessment of quality of life in the younger child: the use of an animated
      computer program.
AB  - BACKGROUND: In the past, quality of life was primarily assessed using objective
      measurements of the condition of the patient. Today, most quality-of-life
      measurements include several aspects regarding the patient's opinions and
      feelings. There has been an extensive development of quality-of-life instruments
      particularly in adults, including those for people with inflammatory bowel
      disease (IBD). However, only a few instruments, mostly questionnaires, have been
      developed for the pediatric population. It has been noted, even in young patients
      with IBD, that there is reduced self-esteem and more anxiety and depression.
      Altogether, these are important aspects for early measurement of psychosocial
      functioning and possibly intervention during the treatment of children with IBD.
      METHODS: For the current study, an instrument was developed for young children
      aged 5 years or more in which a computer-based animated program was used to
      measure quality of life in children with inflammatory bowel disease. The
      instrument was designed to be similar for boys and girls with no reference to
      racial identity. In addition, it was culturally acceptable for all Dutch
      children. The program was in the form of a story of a bear and a clown playing in
      an attic of an old house where they come across many objects with which they play
      and where many adventures occur. All 35 questions were interwoven in this story.
      RESULTS: The animated computer program was well accepted and easily used by 16
      children between the ages of 5 and 12 in a small pilot study. In those older than
      11 years, another approach is probably necessary, using an age-appropriate
      animated program. CONCLUSIONS: The computer program can easily be used in an
      outpatient setting and thus ensures that quality-of-life measurement will become
      a routine part of a medical visit.

PMID- 10204528
TI  - Potential uses for quality-of-life measures in childhood inflammatory bowel
      disease.
AB  - Health-related quality of life (HRQOL) in children with inflammatory bowel
      disease is clearly reduced in the physical as well as in the psychological and
      social functioning domains. However, very few studies of these children have been
      performed from a quality-of-life perspective. Multicenter studies on HRQOL are
      needed to answer questions about the impact of Crohn's disease and ulcerative
      colitis and their treatment and complications on HRQOL in children and
      adolescents and their association with outcome. This article describes
      perspectives from which quality of life studies may be performed, potential uses
      of HRQOL measures, and issues that should be accounted for in designing
      multicenter clinical studies on this topic.

PMID- 10204529
TI  - What causes schizophrenia?

PMID- 10204530
TI  - Experience-dependent development of NMDA receptor transmission.

PMID- 10204531
TI  - A tale of two spikes.

PMID- 10204532
TI  - BMPs: time to murder and create?

PMID- 10204533
TI  - Anandamide: a candidate neurotransmitter heads for the big leagues.

PMID- 10204534
TI  - Nerve growth factor acts via retinoic acid synthesis to stimulate neurite
      outgrowth.

PMID- 10204535
TI  - A molecular correlate of memory and amnesia in the hippocampus.

PMID- 10204536
TI  - Frontal cortex contributes to human memory formation.
AB  - The contribution of medial temporal lobe structures to memory is well
      established. However recent brain-imaging studies have indicated that frontal
      cortex may also be involved in human memory formation. Specific frontal areas are
      recruited during a variety of procedures that promote memory formation, and the
      laterality of these areas is influenced by the type of information contained in
      the memory. Imaging methods that capture momentary changes in brain activity have
      further shown that the likelihood of memory formation correlates with the level
      of activity in these areas. These results, taken in the context of other studies,
      suggest that memory formation depends on joint participation of frontal and
      medial temporal lobe structures.

PMID- 10204537
TI  - Pore dilation of neuronal P2X receptor channels.
AB  - P2X receptors are ligand-gated ion channels activated by the binding of
      extracellular adenosine 5'-triphosphate (ATP). Brief (< 1 s) applications of ATP
      to nodose ganglion neurons or to cells transfected with P2X2 or P2X4 receptor
      cDNAs induce the opening of a channel selectively permeable to small cations
      within milliseconds. We now show that, during longer ATP application (10-60 s),
      the channel also becomes permeable to much larger cations such as N-methyl-D
      glucamine and the propidium analog YO-PRO-1. This effect is enhanced in P2X2
      receptors carrying point mutations in the second transmembrane segment.
      Progressive dilation of the ion-conducting pathway during prolonged activation
      reveals a mechanism by which ionotropic receptors may alter neuronal function.

PMID- 10204538
TI  - Neuronal P2X transmitter-gated cation channels change their ion selectivity in
      seconds.
AB  - Fast synaptic transmission depends on the selective ionic permeability of
      transmitter-gated ion channels. Here we show changes in the ion selectivity of
      neuronal P2X transmitter-gated cation channels as a function of time (on the
      order of seconds) and previous ATP exposure. Heterologously expressed P2X2,
      P2X2/P2X3 and P2X4 channels as well as native neuronal P2X channels possess
      various combinations of mono- or biphasic responses and permeability changes,
      measured by NMDG+ and fluorescent dye. Furthermore, in P2X4 receptors, this
      ability to alter ion selectivity can be increased or decreased by altering an
      amino-acid residue thought to line the ion permeation pathway, identifying a
      region that governs this activity-dependent change.

PMID- 10204539
TI  - G-protein-coupled receptors act via protein kinase C and Src to regulate NMDA
      receptors.
AB  - The N-methyl-D-aspartate (NMDA) receptor contributes to synaptic plasticity in
      the central nervous system and is both serine-threonine and tyrosine
      phosphorylated. In CA1 pyramidal neurons of the hippocampus, activators of
      protein kinase C (PKC) as well as the G-protein-coupled receptor ligands
      muscarine and lysophosphatidic acid enhanced NMDA-evoked currents. Unexpectedly,
      this effect was blocked by inhibitors of tyrosine kinases, including a Src
      required sequence and an antibody selective for Src itself. In neurons from mice
      lacking c-Src, PKC-dependent upregulation was absent. Thus, G-protein-coupled
      receptors can regulate NMDA receptor function indirectly through a PKC-dependent
      activation of the non-receptor tyrosine kinase (Src) signaling cascade.

PMID- 10204540
TI  - BMPs inhibit neurogenesis by a mechanism involving degradation of a transcription
      factor.
AB  - Bone morphogenetic proteins (BMPs), negative regulators of neural determination
      in the early embryo, were found to be potent inhibitors of neurogenesis in
      olfactory epithelium (OE) cultures. BMPs 2, 4 or 7 decreased the number of
      proliferating progenitor cells and blocked production of olfactory receptor
      neurons (ORNs). Experiments suggested that this effect was due to an action of
      BMPs on an early-stage progenitor in the ORN lineage. Further analysis revealed
      that progenitors exposed to BMPs rapidly (< 2 h) lost MASH1, a transcription
      factor known to be required for the production of ORNs. This disappearance was
      due to proteolysis of existing MASH1 protein, but new gene expression was
      required to trigger it. The data suggest a novel mechanism of BMP action, whereby
      the induced degradation of an essential transcription factor results in premature
      termination of a neuronal lineage.

PMID- 10204541
TI  - Presynaptic depolarization facilitates neurotrophin-induced synaptic
      potentiation.
AB  - Neurotrophins have been proposed to participate in activity-dependent
      modifications of neuronal connectivity and synaptic efficacy. Preferential
      strengthening of active inputs requires restriction of putative neurotrophin
      mediated synaptic potentiation to active synapses. Here we report that
      potentiation of synaptic efficacy by brain-derived neurotrophic factor (BDNF) is
      greatly facilitated by presynaptic depolarization at developing neuromuscular
      synapses. Brief depolarization in the presence of low-level BDNF results in a
      marked potentiation of both evoked and spontaneous synaptic transmission, whereas
      exposure to either BDNF or depolarization alone is without effect. This
      potentiation depends on the relative timing of depolarization and reflects an
      enhancement of transmitter secretion from the presynaptic neuron. Thus synapses
      made by active inputs may be selectively strengthened by secreted neurotrophins
      as part of activity-dependent refinement of developing connections or of mature
      synapses.

PMID- 10204542
TI  - Rapid, experience-dependent expression of synaptic NMDA receptors in visual
      cortex in vivo.
AB  - Sensory experience is crucial in the refinement of synaptic connections in the
      brain during development. It has been suggested that some forms of experience
      dependent synaptic plasticity in vivo are associated with changes in the
      complement of postsynaptic glutamate receptors, although direct evidence has been
      lacking. Here we show that visual experience triggers the rapid synaptic
      insertion of new NMDA receptors in visual cortex. The new receptors have a higher
      proportion of NR2A subunits and, as a consequence, different functional
      properties. This effect of experience requires NMDA receptor activation and
      protein synthesis. Thus, rapid regulation of postsynaptic glutamate receptors is
      one mechanism for developmental plasticity in the brain. Changes in NMDA receptor
      expression provide a mechanism by which brief sensory experience can regulate the
      properties of NMDA receptor-dependent plasticity in visual cortex.

PMID- 10204543
TI  - Dopamine activation of endogenous cannabinoid signaling in dorsal striatum.
AB  - We measured endogenous cannabinoid release in dorsal striatum of freely moving
      rats by microdialysis and gas chromatography/mass spectrometry. Neural activity
      stimulated the release of anandamide, but not of other endogenous cannabinoids
      such as 2-arachidonylglycerol. Moreover, anandamide release was increased
      eightfold over baseline after local administration of the D2-like (D2, D3, D4)
      dopamine receptor agonist quinpirole, a response that was prevented by the D2
      like receptor antagonist raclopride. Administration of the D1-like (D1, D5)
      receptor agonist SKF38393 had no such effect. These results suggest that
      functional interactions between endocannabinoid and dopaminergic systems may
      contribute to striatal signaling. In agreement with this hypothesis, pretreatment
      with the cannabinoid antagonist SR141716A enhanced the stimulation of motor
      behavior elicited by systemic administration of quinpirole. The endocannabinoid
      system therefore may act as an inhibitory feedback mechanism countering dopamine
      induced facilitation of motor activity.

PMID- 10204544
TI  - Involvement of striate and extrastriate visual cortical areas in spatial
      attention.
AB  - We investigated the cortical mechanisms of visual-spatial attention while
      subjects discriminated patterned targets within distractor arrays. Functional
      magnetic resonance imaging (fMRI) was used to map the boundaries of retinotopic
      visual areas and to localize attention-related changes in neural activity within
      several of those areas, including primary visual (striate) cortex. Event-related
      potentials (ERPs) and modeling of their neural sources, however, indicated that
      the initial sensory input to striate cortex at 50-55 milliseconds after the
      stimulus was not modulated by attention. The earliest facilitation of attended
      signals was observed in extrastriate visual areas, at 70-75 milliseconds. We
      hypothesize that the striate cortex modulation found with fMRI may represent a
      delayed, re-entrant feedback from higher visual areas or a sustained biasing of
      striate cortical neurons during attention. ERP recordings provide critical
      temporal information for analyzing the functional neuroanatomy of visual
      attention.

PMID- 10204545
TI  - A physiological correlate of the 'spotlight' of visual attention.
AB  - Here we identify a neural correlate of the ability to precisely direct visual
      attention to locations other than the center of gaze. Human subjects performed a
      task requiring shifts of visual attention (but not of gaze) from one location to
      the next within a dense array of targets and distracters while functional MRI was
      used to map corresponding displacements of neural activation within visual
      cortex. The cortical topography of the purely attention-driven activity precisely
      matched the topography of activity evoked by the cued targets when presented in
      isolation. Such retinotopic mapping of attention-related activation was found in
      primary visual cortex, as well as in dorsomedial and ventral occipital visual
      areas previously implicated in processing the attended target features. These
      results identify a physiological basis for the effects of spatially directed
      visual attention.

PMID- 10204546
TI  - Attention activates winner-take-all competition among visual filters.
AB  - Shifting attention away from a visual stimulus reduces, but does not abolish,
      visual discrimination performance. This residual vision with 'poor' attention can
      be compared to normal vision with 'full' attention to reveal how attention alters
      visual perception. We report large differences between residual and normal visual
      thresholds for discriminating the orientation or spatial frequency of simple
      patterns, and smaller differences for discriminating contrast. A computational
      model, in which attention activates a winner-take-all competition among
      overlapping visual filters, quantitatively accounts for all observations. Our
      model predicts that the effects of attention on visual cortical neurons include
      increased contrast gain as well as sharper tuning to orientation and spatial
      frequency.

PMID- 10204547
TI  - Emotional responses to pleasant and unpleasant music correlate with activity in
      paralimbic brain regions.
AB  - Neural correlates of the often-powerful emotional responses to music are poorly
      understood. Here we used positron emission tomography to examine cerebral blood
      flow (CBF) changes related to affective responses to music. Ten volunteers were
      scanned while listening to six versions of a novel musical passage varying
      systematically in degree of dissonance. Reciprocal CBF covariations were observed
      in several distinct paralimbic and neocortical regions as a function of
      dissonance and of perceived pleasantness/unpleasantness. The findings suggest
      that music may recruit neural mechanisms similar to those previously associated
      with pleasant/unpleasant emotional states, but different from those underlying
      other components of music perception, and other emotions such as fear.

PMID- 10204548
TI  - Initial experience with the advanced breast biopsy instrumentation system.
AB  - BACKGROUND: Advanced breast biopsy instrumentation is a recently designed
      alternative to large-core stereotactic and open needle localized breast biopsies.
      This minimally invasive technique uses digital stereotactic imaging to perform
      excisional biopsies of suspicious, nonpalpable mammographic lesions. The role of
      the ABBI system in the management of breast cancer has not yet been defined.
      METHODS: A retrospective review to evaluate the safety, accuracy, and cost
      effectiveness of the ABBI system as performed by a single surgeon on 107 patients
      from February 1, 1997 to January 31, 1998. We also discuss the use of the ABBI
      system as a therapeutic breast cancer technique. All patients had nonpalpable
      mammographic lesions. The mammographic abnormalities were either architectural
      distortion, microcalcifications, or stellate and nodular densities. RESULTS:
      Using the ABBI stereotactic unit, 110 breast biopsies were performed in 107
      patients during a 12-month period. The mammographic abnormality was accurately
      localized and successfully biopsied in 99% (109 of 110) of the procedures as
      confirmed by specimen radiographs, stereotactic images, permanent pathologic
      sections, and 6-month follow-up mammograms. There were no intraoperative
      complications. Two patients developed postoperative wound hematomas and there was
      1 postoperative wound infection. Six in situ cancers and 21 invasive cancers were
      diagnosed with the ABBI system. Two additional invasive cancers were diagnosed in
      patients with ductal carcinoma in situ at reexcision. Four patients with invasive
      ductal carcinoma and 1 patient with ductal carcinoma in situ had negative margins
      on their stereotactic biopsies and did not undergo reexcision by lumpectomy or
      mastectomy. Each of the 4 patients with invasive ductal carcinoma underwent
      axillary node dissections with postoperative radiation therapy and chemotherapy
      or tamoxifen. During the study period, the average hospital patient charge for a
      stereotactic breast biopsy was $2,377.75, and for an open excisional needle
      localized biopsy it was $3,028.00 (P <0.05). The stereotactic breast biopsy
      offered a total cost savings of $71,527.50 in our series of patients. CONCLUSION:
      Advanced breast biopsy instrumentation is a safe, accurate, and cost-effective
      method for performing breast biopsies. In addition, the ABBI system may be able
      to excise small in situ or invasive breast cancers.

PMID- 10204549
TI  - Experience with endovascular grafts in the treatment of infrarenal aortic
      aneurysms associated with proximal aortic dissection.
AB  - BACKGROUND: Chronic abdominal and thoracic aortic dissections often present with
      concomitant infrarenal aortic dilatation. We conducted a retrospective review of
      6 patients treated with endovascular stent grafts for coexisting aortic
      dissection and infrarenal aneurysm. METHODS: Six patients with suprarenal aortic
      dissections and infrarenal aortic aneurysms (AAA) had their AAAs treated with
      endovascular grafts. Grafts were constructed of balloon expandable Palmaz stents
      and expanded polytetrafluoroethylene graft. The device was inserted
      transfemorally and deployed under fluoroscopy. RESULTS: Successfully primary AAA
      exclusion was achieved in 5 patients. One patient required a supplemental stent
      placed above the endograft and into the true lumen to seal the endoleak. No
      aneurysm has enlarged, and all remain thrombosed for 9 to 24 months (mean 20).
      One type III dissection enlarged 2 weeks after endograft insertion. One patient
      had uncomplicated cephalad fenestration of a dissection by the endograft.
      CONCLUSIONS: Endovascular grafts may be used to treat coexisting AAA and aortic
      dissection. Attention to the site or sites of reentry of a dissection is
      essential to insure full aortic aneurysm exclusion. The fate of a chronic aortic
      dissection cephalad to an endovascularly treated AAA is unclear and will require
      longer follow-up.

PMID- 10204550
TI  - Fundoplications resist reflux independent of in vivo anatomic relationships.
AB  - BACKGROUND: Antireflux operations restore lower esophageal sphincter (LES)
      function and hiatal anatomy; however, the relative contributions are unclear.
      METHODS: We measured the competency of fundoplications, exclusive of in vivo
      variables, in gastroesophageal explants from 8 cadavers. Using a multichannel
      manometer, esophageal, LES, and intragastric pressures were recorded during
      transpyloric distension. Data were compared at baseline, and after Nissen (360
      degrees) and Toupet (270 degrees) fundoplications. RESULTS: Before
      fundoplication, stomachs refluxed immediately upon distension. Nissen
      fundoplications never refluxed before gastric rupture (46.8 +/- 15.0 mm Hg). LES
      pressure averaged 2.0 +/- 0.5 times intragastric pressure during distension.
      Toupet fundoplications refluxed at intragastric pressure <2 mm Hg, then became
      competent until gastric rupture (49.9 +/- 15.0 mm Hg). LES pressure averaged 2.4
      +/- 1.0 times intragastric pressure during distension. CONCLUSIONS: Nissen and
      Toupet fundoplications increase LES pressure linearly at 2 to 2.5 times
      intragastric pressure, independent of in vivo variables. Toupet fundoplication
      lacks the competency of Nissen fundoplication at low intragastric pressures.

PMID- 10204551
TI  - Influence of popliteal vein thrombosis on subsequent ambulatory venous function
      measured by near-infrared spectroscopy.
AB  - BACKGROUND: To determine the influence of the site affected by thrombi on the
      subsequent venous physiology, we examined patients with postthrombotic syndrome
      (PTS) with respect to ambulatory venous function using near-infrared spectroscopy
      (NIRS). METHODS: Fifty-one limbs of 45 patients, for whom more than 1 year had
      passed since an acute episode of deep vein thrombosis, were studied. Seventeen
      limbs were asymptomatic, 27 had mild symptoms (edema only), and 7 showed severe
      symptoms (skin changes). The mean duration of PTS was 8.2 years. All of the
      patients underwent a treadmill walking test with simultaneous NIRS. Deoxygenated
      hemoglobin was continuously measured during exercise. The ambulatory venous
      retention index (AVRI) obtained from the serial deoxygenated hemoglobin changes
      was calculated in each patient. The location of thrombi at the onset of deep vein
      thrombosis was identified by venography. RESULTS: The calculated AVRI was
      apparently related to the clinical symptoms of PTS. The limbs initially involved
      with popliteal vein thrombosis showed significantly higher AVRI values than those
      without popliteal vein thrombosis. CONCLUSIONS: The clinical severity of PTS is
      correlated well with the degree of venous retention during exercise. Initial
      involvement of the popliteal vein is an important factor determining subsequent
      venous hemodynamics in patients with PTS.

PMID- 10204552
TI  - Intraductal papillary mucinous tumor of the pancreas.
AB  - BACKGROUND: Since 1996 the classification of pancreatic tumors was replaced by
      the new World Health Organization nomenclature. Formerly mucinous cystadenomas
      are now distinguished between intraductal papillary mucinous tumors of the
      pancreas (IPMT) and mucinous cystadenomas. METHODS: We reevaluated the
      pathological specimen and surgical therapy of 23 consecutive patients and
      followed up these patients up for 4 years in median. Between 1987 and 1997 we
      treated 8 patients with IPMT and 15 patients with mucinous cystadenomas. RESULTS:
      Eighty-five per cent of all patients were symptomatic. Ultrasonography and
      computed tomography were the most sensitive diagnostic techniques. In 25%, the
      entire pancreas was involved with IPMT; that was not the case in any of the
      patients with mucinous cystadenoma. All patients were resected with no
      perioperative mortality. After dismissal from the hospital, all resected patients
      are still alive after a median follow-up of 4 years. In no patient with IPMT, but
      in 1 patient with mucinous cystadenoma, the tumor recurred. CONCLUSION: Surgical
      resection is the treatment of choice in all cystic tumors, and the late outcome
      of IPMT is as good as for mucinous cystadenoma.

PMID- 10204553
TI  - Repair of pectus excavatum and carinatum in adults.
AB  - BACKGROUND: There is sparse published information regarding the repair of pectus
      chest deformities in adults. This report summarizes our clinical experience with
      the surgical repair of pectus excavatum and carinatum deformities in 25 adults.
      METHODS: During the past 11 years, 25 patients 20 years of age or older (mean 31)
      with symptomatic pectus excavatum (23) or carinatum (2) deformities underwent
      surgical repair using a temporary internal sternal support bar. RESULTS: Each of
      the patients with decreased stamina and endurance or dyspnea with exercise
      experienced marked clinical improvement within 4 months postoperation. Exercise
      induced asthma was improved in 6 of 7 patients; chest pain was reduced in each of
      9 patients. Postoperative complications included pneumothorax (1), keloid (2),
      and discomfort from sternal bar (2). The sternal bar was removed 7 to 10 months
      postoperation in 19 patients; there has been no return of preoperative symptoms
      or recurrent depression in any patient with a mean follow-up of 4.8 years.
      CONCLUSIONS: For adults who have symptoms and activity limitations related to
      uncorrected pectus chest deformities, surgical repair can be performed with low
      morbidity, low cost, minimal limitation in activity, and a high frequency of
      symptomatic improvement. The operation in adults is more difficult than in
      children, although the results are similar.

PMID- 10204555
TI  - Are long hours and hard work detrimental to end-clerkship examination scores?
AB  - BACKGROUND: Third-year medical students' complaints focus on the number of hours
      worked and subsequent lack of study time among three general surgery blocks. We
      hypothesize that this difference between the surgical blocks does not adversely
      influence student examination scores. METHODS: Student scores for the academic
      years 1996-97 to 1997-98 for the National Board of Medical Examiners (NBME)
      surgery subtests were compiled. A comparison of two "slow" general surgery blocks
      (B/C) with one "busy" block (A) was made using a two-tailed t test. A multiple
      regression analysis was also employed. Finally, United States Medical Licensing
      Examination (USMLE) part I scores were used to determine equivalency of groups.
      RESULTS: No significant difference existed between block A and blocks B/C in
      USMLE part I and NBME (P = 0.35 and 0.16 respectively). However, USMLE and
      rotation sequence influenced NBME scores (P < 0.001). CONCLUSION: The data
      suggest that no difference exists in examination scores between students assigned
      to a busy general surgery block versus those students assigned to slow blocks.

PMID- 10204554
TI  - The duration of antibiotic administration in penetrating abdominal trauma.
AB  - BACKGROUND: The epidemiology of penetrating abdominal trauma is changing to
      reflect an increasing incidence of multiple injuries. Not only do multiple
      injuries increase the risk of infection, a very high risk of serious infection is
      conferred by immunosuppression from hemorrhage and transfusion and the high
      likelihood of intestinal injury, especially to the colon. Optimal timing and
      choice of presumptive antibiotic therapy has been established for penetrating
      trauma, but duration has not been studied extensively in such seriously injured
      patients. The purpose of this study was to test the hypothesis that 24 hours of
      antibiotic therapy remains sufficient to reduce the incidence of infection in
      penetrating abdominal trauma. METHODS: Three hundred fourteen consecutive
      patients with penetrating abdominal trauma were prospectively randomized into two
      groups: Group I received 24 hours of intravenous cefoxitin (1 g q6h) and group II
      received 5 days of intravenous cefoxitin. The development of a deep surgical site
      (intra-abdominal) infection as well as any type of nosocomial infection, as
      defined by the Centers for Disease Control and Prevention, (ie, surgical site
      infections, catheter-related infections, urinary tract, pneumonia), was recorded.
      Hospital length of stay was a secondary endpoint. Statistical analysis included
      chi-square tests for coordinate variables and two-tailed unpaired t tests for
      continuous variables. The independence of risk factors for the development of
      infection was assessed by multivariate analysis of variance. Significance was
      determined when P <0.05. RESULTS: Three hundred patients were evaluable. There
      was no postoperative mortality, and no differences in overall length of
      hospitalization between groups. The duration of antibiotic treatment had no
      influence on the development of any infection (P = 0.136) or an intraabdominal
      infection (P = 0.336). Only colon injury was an independent predictor of the
      development of an intraabdominal infection (P = 0.0031). However, the overall
      infection incidence was affected by preoperative shock (P = 0.003), colon (P =
      0.0004), central nervous system (CNS) injuries (P = 0.031), and the number of
      injured organs (P = 0.026). Several factors, including intraoperative shock (P =
      0.021) and injuries to the colon (P = 0.0008), CNS (P = 0.0001), and chest (P =
      0.0006), were independent contributors to prolongation of the hospital stay.
      CONCLUSIONS: Twenty-four hours of presumptive intravenous cefoxitin versus 5 days
      of therapy made no difference in the prevention of postoperative infection or
      length of hospitalization. Infection was associated with shock on admission to
      the emergency department, the number of intra-abdominal organs injured, colon
      injury specifically, and injury to the central nervous system. Intra-abdominal
      infection was predicted only by colon injury. Prolonged hospitalization was
      associated with intraoperative shock and injuries to the chest, colon, or central
      nervous system.

PMID- 10204556
TI  - Faculty and resident opinions regarding the role of morbidity and mortality
      conference.
AB  - BACKGROUND: The role of the surgical morbidity and mortality (M&M) conference as
      a forum for examination of surgical failure may remain unclear. This paper
      reports the results of a national survey of surgical faculty and trainees
      regarding the role and effectiveness of the M&M conference. METHODS: Based on
      focus groups and pilot studies from multiple institutions in one geographic area,
      a questionnaire addressing critical issues in attitudes toward the M&M conference
      was sent to 1,100 randomly chosen subjects nationwide: 500 residents and 600
      staff. The survey includes individual and institutional demographic information,
      15 statements answered using a Likert scale, and 2 open-ended questions. RESULTS:
      Faculty response rate was 501 of 600 (83%) and resident response rate was 166 of
      500 (33%). Responses were generally positive in both groups, with staff showing
      small but significantly more positive attitudes than residents. A higher
      proportion of residents characterize the M&M conference as too defensive.
      CONCLUSION: The M&M conference is fulfilling its potential as a teaching tool but
      there may be room for improvement as residents view the experience slightly less
      positively than faculty. This questionnaire provides a perspective of
      expectations for the M&M conference, allowing educators to optimize its
      effectiveness.

PMID- 10204557
TI  - What is the "ideal" grading system for the junior surgery clerkship?
AB  - BACKGROUND: There is currently no consistency in grading systems for clinical
      clerkships across medical schools. METHODS: Surgery clerkship directors were
      surveyed regarding their current grading categories, distribution of grades
      across levels, and opinions about the "ideal" grading system. RESULTS: Responses
      were received from 103 of 134 schools (77%). The following grading systems were
      employed: numerical scores, 1%; points, 1%; pass/fail, 5%; letter grades, 19%;
      and descriptor terms, 74%. Institutions used the following number of grading
      categories: 2, 5%; 3, 18%; 4, 35%; 5, 37%; 6, 3%; and 7, 1%. There was
      considerable variation between schools in frequency distributions across levels.
      Half of clerkship directors were satisfied with their system, and most considered
      an ideal system to consist of 4 or 5 descriptors. CONCLUSIONS: We believe an
      optimal clerkship grading system should consist of 4 or 5 categories. A 3-level
      system does not sufficiently discriminate, and with more than 5 categories the
      lowest levels are rarely used. Grades must be reported with clear information
      about their significance in each institution.

PMID- 10204558
TI  - Subcutaneous access ports with fenestrated catheters for improved management of
      recurrent pleural effusions.
AB  - Repeated percutaneous thoracentesis can involve serious complications, such as
      pneumothorax or infection. Alternatives such as placement of chest tubes or
      pleurodesis have their own potential complications. Creative options such as
      pleuroperitoneal shunting and video thoracoscopy have previously been used to
      avoid the disadvantages of repeated percutaneous thoracentesis. This paper
      describes an easy and effective method for managing these patients without
      repeated percutaneous thoracentesis. A port is inserted that can be accessed
      percutaneously and immediately for needed aspirations. We have successfully
      performed this procedure on 6 patients. Our hope is that the easy access using a
      short needle into the port aperture will allow the thoracentesis to be performed
      by appropriately instructed and supervised paramedical personnel. Also, with
      fewer postprocedure chest radiographs or hemothoraceses, future benefits from
      this procedure could include cost effectiveness.

PMID- 10204559
TI  - Tube loop (seton) drainage treatment of recurrent extrasphincteric perianal
      fistulae.
AB  - Tube loop seton drainage treatment of multiply recurring high-spreading
      extrasphincteric perianal fistulae in 19 patients is reported in this study. The
      drainage loop setons make possible the rinsing of the wound following
      fistulectomy and also the bidirectional drainage of the wound discharge.
      Strangulation of the wound and an early closure of the fistula and hence the
      development of recurrence is prevented by means of controlled formation of
      scarred tissue. The sphincteral musculature of the anus is also protected from
      damage. Thirty-five recurring fistulae of 19 patients included in the present
      study were treated successfully by this method. Two fistula recurred. None of
      these patients developed incontinence. The use of tube loop setons was found to
      have advantages over the pull-out method in cases of high-spreading multiply
      recurring extrasphincteric or suprasphincteric perianal fistulae.

PMID- 10204560
TI  - Decision making on surgical palliation based on patient outcome data.
AB  - BACKGROUND: Strategies for the effective application of palliative procedures are
      infrequently standardized and incompletely understood. The effect on patient
      outcome as determined by elements such as resolution of chief complaints, quality
      of life, pain control, morbidity of therapy, and resource utilization should
      predominate decisions regarding surgical palliative care. METHODS: Articles
      published between 1990 and 1996 on the surgical palliation of cancer were
      identified by a MEDLINE search and reviewed for designated parameters considered
      important for good palliative care. RESULTS: A total of 348 citations were
      included. Entries considered these fundamental elements: cost (2%); pain control
      (12%); quality of life (17%); need to repeat the intervention (59%); morbidity
      and mortality (61 %); survival (64%); and physiologic response (69%). Established
      methods for quality of life and pain assessment were sporadically utilized.
      CONCLUSIONS: In the current surgical literature, there is uncommon reporting of
      the range of data required to recommend sound palliative surgical choices.

PMID- 10204561
TI  - Laparoscopic floppy Nissen fundoplication.
AB  - Good results for antireflux surgery are obtained when proper patients are
      selected, trained surgeons perform the operation, and proper techniques are used.
      As our prior results showed higher rates of dysphagia without fundus mobilization
      (Nissen-Rossetti fundoplication), we now perform complete mobilization on all
      patients. Full fundus mobilization requires take-down of the short gastric
      vessels to reveal the base of the left crus, take-down of all posterior
      gastropancreatic adhesions and the peritoneal fold that is cauded to the crus and
      superior to the pancreas. Proper division of these attachments will allow an
      untethered fundoplication and may reduce the risk of dysphagia and slip of the
      fundoplication onto the stomach.

PMID- 10204562
TI  - Laparoscopic pancreatic surgery.
AB  - BACKGROUND: Potential applications for laparoscopic surgery in pancreatic disease
      include (1) staging of pancreatic malignancies; (2) palliation of pancreatic
      malignancies; (3) pancreatic resections for benign and malignant disease; and (4)
      pancreatic drainage procedures. METHODS: A review of the literature is presented.
      In addition, original data on a series of 5 laparoscopic pancreatic distal
      resections and 10 laparoscopic cystogastrostomies are presented. RESULTS AND
      CONCLUSIONS: Laparoscopy may have a role in the staging of patients with
      pancreatic malignancies; however, with high-quality preoperative imaging, the
      percentage of patients who will benefit from laparoscopy may be as low as 5%. For
      palliation, both cholecystoenterostomy and choledochoenterostomy can be performed
      laparoscopically. The former is technically straightforward but has a higher
      failure rate; the latter is technically difficult and currently not suitable for
      widespread adoption. Laparoscopic gastroenterostomy is a straightforward means of
      palliating gastrointestinal obstruction. Patients appear to benefit from
      laparoscopic distal pancreatic resection but not from laparoscopic
      pancreaticoduodenectomy. Patients appear to benefit from laparoscopic pseudocyst
      decompression.

PMID- 10204563
TI  - The effects of retroperitoneal carbon dioxide insufflation on hemodynamics and
      arterial carbon dioxide.
AB  - BACKGROUND: Laparoscopic techniques are being increasingly used for
      retroperitoneal surgery. However, hemodynamic and ventilatory efforts of
      retroperitoneal carbon dioxide (CO2) insufflation have not been studied. We
      hypothesized that differences in absorptive surface, anatomy, and compartment
      compliance could result in different hemodynamic and ventilatory effects between
      retroperitoneal and intraperitoneal insufflation. METHODS: Pigs (n = 7) were
      anesthetized and stabilized. The peritoneal cavity was incrementally insufflated
      with CO2 to a maximum pressure of 25 cm H2O and the gas released. Hemodynamics
      and arterial blood gas values were recorded initially, at each level of
      insufflation, and following the pneumoperitoneum release until baseline values
      were reached. This insufflation protocol was repeated in the retroperitoneum.
      RESULTS: Mean arterial pressure (111 mm Hg, 95% confidence interval 99 to 156)
      and cardiac output (3.7 L/min, 2.8 to 5.2) did not change with increasing
      insufflation pressure of either intraperitoneum or retroperitoneum. PaCO2 was
      directly related to insufflation pressure in both spaces, increasing from 41.2 mm
      Hg (37.3 to 43.4) at baseline to 57.7 mm Hg (47.6 to 82.1) at insufflation
      pressure of 25 cm H2O. After release of the insufflation gas, time to return to
      baseline PaCO2 was slightly less from the retroperitoneal space (73 minutes, 45
      to 105) than the intraperitoneal (107 minutes, 35 to 175). CONCLUSIONS: The
      effects of CO2 insufflation on hemodynamics and PaCO2 are the same in the
      retroperitoneal and intraperitoneal spaces.

PMID- 10204564
TI  - Assessment of technical skills transfer from the bench training model to the
      human model.
AB  - BACKGROUND: This study examines whether technical skills learned on a bench model
      are transferable to the human cadaver model. METHODS: Twenty-three first-year
      residents were randomly assigned to three groups receiving teaching on six
      procedures. For each procedure, one group received training on a cadaver model,
      one received training on a bench model, and one learned independently from a
      prepared text. Following training, all residents were assessed on their ability
      to perform the six procedures. RESULTS: Repeated measures analysis of variance
      revealed a significant effect of training modality for both checklist scores
      (F(2,44) = 3.49, P <0.05) and global scores (F(2,44) = 7.48, P <0.01). Post-hoc
      tests indicated that both bench and cadaver training were superior to text
      learning and that bench and cadaver training were equivalent. CONCLUSIONS:
      Training on a bench model transfers well to the human model, suggesting strong
      potential for transfer to the operating room.

PMID- 10204565
TI  - A virtual reality module for intravenous catheter placement.
AB  - BACKGROUND: Virtual reality (VR) is a potential tool for technical skills
      training. We tested the validity and instructional effectiveness of a prototype
      VR module for learning intravenous (i.v.) catheter placement. METHODS: First-year
      medical students (n = 37), third-year medical students (n = 14), and surgical
      residents (n = 9) attempted two pretest i.v.s into each other, used the VR module
      for 12 minutes, and subsequently attempted two posttest i.v.s. Success or failure
      were recorded for each attempt. For each successful attempt, time and global
      rating of i.v. insertion were also recorded. RESULTS: The pretest success rate
      was significantly different between groups (chi square = 28.71, P <0.01). VR
      success rate was not significantly different between groups (F(2,57) = 1.47, ns).
      Although there was improvement in all groups during VR training (F(2,114) =
      44.16, P <0.01), this did not result in improvement in posttest performance.
      CONCLUSIONS: Significant differences between groups were observed in performance
      of i.v. insertion in physical reality. However, no significant difference was
      observed in performance in VR. Thus, performance in VR demonstrated neither
      construct nor concurrent validity. While performance improved in VR, transfer of
      skill from VR to physical reality was not observed. Additional development and
      testing of VR as a training tool is warranted before its widespread use can be
      recommended.

PMID- 10204566
TI  - Superior survival of young women with malignant melanoma.

PMID- 10204567
TI  - Innate and acquired immunity in neurodegenerative disorders.

PMID- 10204568
TI  - Inflammation of the brain in Alzheimer's disease: implications for therapy.
AB  - We briefly describe the similarities and differences between a systemic and a
      local immune reaction and review the evidence that the latter occurs in
      Alzheimer's disease (AD) brains. The evidence comes mainly from studies on the
      complement system, microglia, and cytokines, all of which are important actors in
      the inflammatory process. The evidence is now overwhelming that the complement
      proteins and many of the mediators of inflammation are produced locally by brain
      cells. We will mention briefly the many epidemiological studies indicating that
      the use of anti-inflammatory drugs reduces the incidence and slows the progress
      of AD. Mention will also be made of some recent work on animal models of possible
      relevance to AD and inflammation.

PMID- 10204569
TI  - Insights into the neurodegenerative process of Alzheimer's disease: a role for
      mononuclear phagocyte-associated inflammation and neurotoxicity.
AB  - Since the first description of Alzheimer's disease (AD) in 1907, significant
      progress was made into understanding disease pathophysiology. The enormous effort
      in AD research has translated into the discovery of genetic linkages for disease,
      into elucidating the structure and function of the etiologic beta-amyloid
      protein, and into unraveling the seemingly complex neuroimmunological cascade
      that affects neuronal dysfunction. Although effective therapies do not currently
      exist, many are being developed. We propose that the neuropathogenesis of AD, in
      measure, revolves around the immunological activation of glial cells, which in
      turn leads to alterations in inflammatory neurotoxin production, and ultimately
      to neuronal injury and death. Elucidating the mechanisms involved in such glial
      cell immune activation should provide valuable insights into understanding the
      disease process and in providing effective therapeutics to prevent and/or retard
      the devastating neurodegeneration that afflicts so many of our elderly.

PMID- 10204571
TI  - Interferon response heterogeneity: activation of a pro-inflammatory response by
      interferon alpha and beta. A possible basis for diverse responses to interferon
      beta in MS.
AB  - Interferon gamma (IFN-gamma) stimulates the (pro-inflammatory) type II interferon
      receptor and is known to exacerbate multiple sclerosis (MS). In contrast, IFN
      alpha and IFN-beta are ligands for the (anti-inflammatory) type I interferon
      receptor and are beneficial in some (but not all) patients with MS. Should IFN
      beta elicit a type-II-like pro-inflammatory response, the beneficial effects
      might be attenuated. These studies were undertaken to test this possibility with
      the use of quinolinic acid (QUIN) formation as a measure of type II receptor
      activation. In normal human macrophage cultures, IFN-gamma was the most potent
      stimulus for QUIN formation. Generally, IFN-beta and IFN-alpha were less potent.
      However, an unexpected inter-patient variability was observed. In some subjects,
      IFN-alpha was more potent than IFN-beta. In other subjects, IFN-beta was more
      potent than IFN-alpha. The present data demonstrate an inter-subject variability
      for QUIN production following exposure to the interferons. MS patients who
      demonstrate a pro-inflammatory response to IFN-beta (e.g., increased QUIN) may be
      less likely to benefit from this therapy.

PMID- 10204572
TI  - The cellular immunology of multiple sclerosis.
AB  - Multiple sclerosis (MS) is a neurological disease that affects the central
      nervous system (brain and spinal cord) resulting in debilitating motor and
      sensory dysfunction. Its mean age of onset is 30 years and, with the exception of
      trauma, MS remains the most frequent cause of neurological disabilities for young
      adults. The disease is highly variable in its onset and progression. It may not
      be easily diagnosed, at least in its earliest stages. Significant disability is a
      hallmark of MS. Indeed, up to 50% of patients require walking aids and 10% are
      wheelchair-bound at 15 years after an initial diagnosis. Clinical features
      include deficits in sensory (parasthesias and numbness), motor (difficulties with
      fine movements and gait), balance, bladder, and sexual functions. Although the
      etiology for MS is not yet known, it is thought to be related to microbial,
      genetic, and/or environmental factors. Pathologically, MS is characterized by
      inflammation. An influx of mononuclear cells occurs through a disrupted blood
      brain barrier into an immune-privileged central nervous system. The secretion of
      a variety of inflammatory cytokines and chemokines from glial cells leads to loss
      of myelin, disruption of oligodendrocyte integrity, and axonal loss. These
      events, in large measure, affect progressive neural atrophy. How brain
      inflammatory activities affect transendothelial migration of leukocytes into the
      brain and alter the process of myelination are the focal points for MS research
      activities.

PMID- 10204570
TI  - Viral variant nucleotide sequences help expose leukocytic positioning in the JC
      virus pathway to the CNS.
AB  - The human polyomavirus JCV lytically infects oligodendrocytes of immunosuppressed
      individuals leading to the fatal demyelinating disease termed progressive
      multifocal leukoencephalopathy (PML). Dementia, hemiparesis, and hemianopsia are
      the predominant presenting signs of PML. Asymptomatic JCV infection is common
      worldwide with approximately 80% of adults testing positive for JCV antibodies.
      In addition to the brain, JCV has been shown to infect tonsil, lymphoid, bone
      marrow, and kidney tissues. Viral variants, classified according to the
      nucleotide sequences of their regulatory regions, are being mapped in human
      tissues and cell types to help trace the pathway of JCV from a site of initial
      infection to target oligodendrocytes. In most literature, a dichotomy of the JCV
      regulatory region structure exists by tissue. B lymphocytes, however, have
      demonstrated the capacity to harbor JCV of diverse regulatory regions, which
      helps position their interaction with virus amid every stage of infection and
      implicates a lymphocytic role in latency.

PMID- 10204573
TI  - HIV-1-induced neuronal injury in the developing brain.
AB  - HIV-1 infection of the nervous system causes neuronal injury and death, resulting
      in cognitive, motor, and behavioral dysfunction in both adults and children. In
      infants a characteristic feature of HIV-1 infection is impaired brain growth
      resulting in secondary microcephaly with onset between 2 and 4 months of age.
      This post-natal period of brain development is particularly vulnerable to
      excitotoxic neuronal injury due to the active synaptogenesis and pruning that
      takes place at this age associated with over-expression of excitatory amino acid
      (EAA) receptors. HIV-1 infection of brain microglia and perivascular macrophages
      results in chronic inflammation manifest pathologically as diffuse microglial
      activation and reactive astrogliosis. Several inflammatory products of activated
      microglia, including tumor necrosis factor alpha (TNF-alpha) and platelet
      activating factor (PAF) have been shown to act as neuronal toxins. This toxic
      effect can be antagonized by blocking NMDA (or AMPA) glutamate receptors,
      suggesting that (weak) excitotoxicity leads to oxidative stress, neuronal injury,
      and apoptosis. HIV-1 infection and chronic inflammation may also contribute
      disruption of the blood-brain barrier and could result in further entry into the
      CNS of toxic viral or cellular products or additional HIV-1-infected cells. We
      hypothesize that prolonged microglial activation during HIV-1 infection underlies
      the neuronal injury and impaired brain growth in affected infants. Further
      investigation of the interaction between HIV-1-infected/activated microglia and
      developing neurons seems warranted. The current understanding of HIV
      neuropathogenesis implies that therapeutic strategies should target the sustained
      immune activation in microglia, attempt to repair the integrity of the blood
      brain barrier, and provide "neuroprotection" from excitotoxic neuronal injury.

PMID- 10204574
TI  - Molecular pathway involved in HIV-1-induced CNS pathology: role of viral
      regulatory protein, Tat.
AB  - The broad range of histological lesions associated with HIV-1 are somewhat subtle
      relative to the clinical manifestations that occur as a result of HIV infection.
      Although it is clear that HIV has a causative role in CNS disease, dementia
      appears to be a consequence of the infiltration of inflammatory cells and
      cytokine dysregulation rather than the amount of virus in CNS. The HIV
      transregulatory protein Tat plays an important intracellular as well as
      extracellular role in the dysregulation of cytokines. The cytokines and possibly
      chemokines that are induced by Tat modify the action of astrocytes such that the
      survival of neurons is compromised. Pathogenetic alteration induced by Tat
      involves a series of interactions between circulating monocyte/macrophages,
      endothelial cells, and astrocytes. Cytokine dysregulation induced by viral
      infection and extracellular Tat leads to alterations in expression of adhesion
      molecules and promotes migration of non-infected inflammatory cells into the CNS
      compartment. We demonstrate here that recombinant HIV-1 Tat protein introduced by
      stereotaxic injection into mouse brain can induce pathologically relevant
      alterations including macrophage invasion as well as astrocytosis. The mechanism
      of destruction of the CNS by Tat appears to involve autocrine and paracrine
      pathways that depend not only on Tat, but cytokine and chemokine signaling
      pathways that are altered by viral infection. In this review, we discuss various
      pathogenic effects of Tat in brain cells and provide experimental evidence for an
      increased TNF-alpha level in CSF in mice injected intracerebrally with Tat
      protein.

PMID- 10204575
TI  - The SIV-infected rhesus monkey model for HIV-associated dementia and implications
      for neurological diseases.
AB  - The neuropathogenesis of human immunodeficiency virus (HIV)-associated dementia
      has remained elusive, despite identification of HIV as the causal agent. Although
      a number of contributing factors have been identified, the series of events that
      culminate in motor and cognitive impairments after HIV infection of the central
      nervous system (CNS) are still not known. Rhesus monkeys infected with simian
      immunodeficiency virus (SIV) manifest immunosuppression and CNS disease that is
      pathologically [L. R. Sharer et al. (1991) J. Med. Primatol. 20, 211-217] and
      behaviorally [E. A. Murray et al. (1992) Science 255, 1246-1249] similar to
      humans. The SIV model of HIV-associated dementia (HAD) is widely recognized as a
      highly relevant model in which to investigate neuropathogenesis. With better
      understanding of neuropathogenesis comes the opportunity to interrupt progression
      and to design better treatments for HAD. This becomes increasingly important as
      patients live longer yet still harbor HIV-infected cells in the CNS. The use of
      the SIV model has allowed the identification of neurochemical markers of
      neuropathogenesis important not only for HAD, but also for other inflammatory
      neurological diseases.

PMID- 10204576
TI  - Do alcohol and cocaine abuse alter the course of HIV-associated dementia complex?
AB  - Although psychoactive drugs are commonly used by AIDS patients, it is unclear
      whether commonly abused drugs, such as cocaine and ethanol, affect the course of
      HIV-associated dementia (HADC). Epidemiological studies have resulted in
      conflicting conclusions as to what role, if any, abused drugs play in HADC. In
      this review we discuss the clinical and pathological evidence that cocaine and
      ethanol might exacerbate the detrimental effects of HIV infection on the brain.
      We also review studies of cocaine and ethanol effects on various components of
      the immune system both in the presence and absence of retroviral infection. Data
      from these studies indicate that cocaine and ethanol have profound effects on the
      immune system that, in many respects, are enhanced by retroviral infection. We
      conclude that abused drugs likely affect the course of HADC but that proof awaits
      an examination of their interactive effects in an appropriate in vivo system of
      retroviral encephalitis.

PMID- 10204577
TI  - Functional roles of MCP-1 in Propionibacterium acnes-induced, T cell-mediated
      pulmonary granulomatosis in rabbits.
AB  - The immunological manifestation of granuloma formations in humans largely depends
      on the delayed-type hypersensitivity response. We investigated the involvement of
      monocyte chemoattractant protein-1 (MCP-1) in a rabbit model of T cell-mediated
      pulmonary granulomatosis. Intravenous injection of Propionibacterium acnes (P.
      acnes) into sensitized rabbits induced massive and diffuse pulmonary granulomas.
      Levels of MCP-1 in sera and bronchoalveolar lavage fluids (BALF) peaked before
      the granuloma formation reached the peak (on days 1 and 3 after challenge,
      respectively). Chemotactic activities toward monocytes and T cells in BALF were
      inhibited by anti-MCP-1 IgG by 80 and 36%, respectively. The phenotypic analysis
      of the migrating T cells revealed that activated and memory T cells rather than
      naive cells were preferentially attracted to the BALF. Administration of anti-MCP
      1 antiserum inhibited the development of granuloma formation in both size and
      number, the numbers of infiltrating leukocytes in BALF, the expression of
      adhesion molecules on peripheral monocytes/T cells, and on macrophages/T cells in
      BALF, and the production of TNF-alpha in the lung. Anti-MCP-1 resulted in a trend
      toward decreased level of IL-1beta in the lung. The inhibition of the production
      of these cytokines appeared to be induced indirectly through the inhibition of
      the recruitment of macrophages that produce these cytokines. The results suggest
      important roles of MCP-1 in the development of granuloma formation in this model
      through the attraction and activation of specific types of cells.

PMID- 10204578
TI  - Macrophage invasion does not contribute to muscle membrane injury during
      inflammation.
AB  - Previous observations have shown that neutrophil invasion precedes macrophage
      invasion during muscle inflammation and that peak muscle injury is observed at
      the peak of ED1+ macrophage invasion. We tested the hypothesis that neutrophil
      invasion causes subsequent invasion by ED1+ macrophages and that ED1+ macrophages
      then contribute significantly to muscle membrane injury during modified muscle
      use. Rat hindlimbs were unloaded for 10 days followed by reloading by normal
      ambulation to induce inflammation. Membrane injury was measured by assaying Evans
      blue-bound serum protein influx through membrane lesions. Muscle neutrophil
      populations increased significantly during the first 2 h of reloading but ED1+
      macrophages did not increase until 24 h. Neutrophil invasion was uncoupled from
      subsequent macrophage invasion by reloading rat hindlimbs for 2 h to cause
      neutrophil invasion, followed by resuspension for hours 2-24. This produced
      similar increases in neutrophil concentration as measured in muscles continuously
      reloaded for 24 h without causing an increase in macrophages. However,
      resuspension did not reduce the extent of muscle damage compared with that
      occurring in muscles that were reloaded continuously for 24 h. Thus, muscle
      invasion by neutrophils is not sufficient to cause invasion by ED1+ macrophages.
      In addition, muscle membrane injury that occurs during reloading is independent
      of invasion by ED1+ macrophages.

PMID- 10204579
TI  - Intracellular oxidant production and cytokine responses in lung macrophages:
      evaluation of fluorescent probes.
AB  - The fluorescent probes dichlorofluorescin (DCFH), dihydrorhodamine (DHR), and
      hydroethidine (HE) allow convenient assay of alveolar macrophage (AM) oxidant
      responses to enviromental particulates and pathogens. We sought to more precisely
      define the relationship of these measures of oxidant stress to production of pro
      inflammatory cytokines. Normal AMs were challenged in vitro with a panel of
      soluble or particulate stimuli in the presence of DCFH, HE, or DHR. Flow
      cytometry measured cell-associated fluorescence and relative particle uptake.
      Tumor necrosis factor alpha and macrophage inflammatory protein 2 expression were
      quantitated in the same experiments. We observed variable and complex
      correlations between intracellular oxidant production as reported by these probes
      and subsequent cytokine response, including examples of striking discordance
      (e.g., lipopolysaccharide induced large cytokine responses with minimal probe
      oxidation, whereas fly ash particles caused marked oxidation of DCFH but trivial
      TNF release; TiO2 caused oxidation of DHR and HE, but not DCFH, and also did not
      increase cytokine production). Although fluorescent probes offer many advantages
      in analysis of intracellular oxidant responses, the data indicate that they
      cannot be used reliably as quantitative predictors of AM cytokine responses to
      environmental particulates or other stimuli.

PMID- 10204580
TI  - Induction of NOS in rat blood PMN in vivo and in vitro: modulation by tyrosine
      kinase and involvement in bactericidal activity.
AB  - Intravenous administration of lipopolysaccharide (LPS) to rats increased the
      production of nitric oxide (NO) metabolites (NOx) by blood polymorphonuclear
      neutrophils (PMN) in vitro. Both dexamethasone and L-NMMA, added in vitro to
      neutrophil cultures, inhibited the production of NO. On the other hand, the
      production of NO was not affected by the treatment, in vivo or in vitro, with
      different inhibitors of cyclooxygenase or 5-lipoxygenase or with a platelet
      activating factor (PAF) antagonist. The incubation of blood PMN from normal rats
      in vitro with neutrophil activators (PAF, leukotriene B4, and interleukin-8) and
      different cytokines [interleukin-1, tumor necrosis factor alpha, and interferon
      gamma (IFN-gamma)] showed that only IFN-gamma was able to induce the production
      of high amounts of NO. This induction was directly correlated with the expression
      of iNOS and an increase in in the enzyme activity in blood PMN. The tyrosine
      kinase inhibitor genistein inhibited NO production induced by IFN-gamma,
      suggesting that the signal transduction pathway leading to NOS induction in rat
      PMN involves phosphorylation by tyrosine kinase. We also showed that NO produced
      by IFN-gamma activated rat blood PMN involved in the killing of Pseudomonas
      aeruginosa.

PMID- 10204581
TI  - Heterologous desensitization of IL-8-mediated chemotaxis in human neutrophils by
      a cell-binding fragment of fibronectin.
AB  - In this study, we have explored the mechanism for the desensitization of IL-8
      mediated neutrophil chemotaxis by a cell-binding fragment of fibronectin (120-kDa
      FN). Preincubation of neutrophil suspensions with the 120-kDa FN fragment
      resulted in a heterologous desensitization of IL-8-mediated chemotaxis while not
      affecting neutrophil chemotaxis to either fMLP or zymosan-activated serum.
      Preincubation of neutrophils with the beta1-integrin-activating antibody (TS2/16)
      mimicked the effects of the 120-kDa FN fragment while preincubating neutrophils
      with the beta1-integrin blocking antibody (mAb13) abrogated the inhibitory
      effects of the 120-kDa FN fragment on IL-8-mediated chemotaxis. Furthermore, we
      also demonstrated that the 120-kDa FN fragment did not inhibit chemotaxis to the
      CXC chemokine MGSA/GROalpha which interacts with high affinity to the IL-8
      receptor B (CXCR2). By in vivo phosphorylation of neutrophils and probing lysates
      with an anti-CXCR1 antibody, we demonstrated that the addition of the cell
      binding fragment of fibronectin resulted in a time-dependent phosphorylation of
      CXCR1. These findings suggest that the mechanism of heterologous desensitization
      of IL-8-mediated chemotaxis following ligation of FN-dependent integrins is the
      result of phosphorylation of the CXCR1 receptor.

PMID- 10204583
TI  - Antibody screening: elimination of another piece of the test.

PMID- 10204582
TI  - Cbl functions downstream of Src kinases in Fc gamma RI signaling in primary human
      macrophages.
AB  - Cbl is a cytosolic protein that is rapidly tyrosine phosphorylated in response to
      Fc receptor activation and binds to the adaptor proteins Grb2, CrkL, and Nck. A
      few reports describe Cbl interactions in primary human hematopoietic cells. We
      show evidence that Cbl participates in signaling initiated by Fc gammaRI receptor
      cross-linking in human primary macrophages, and functions downstream of Src
      family kinases in this pathway. Fc gammaRI stimulation in human macrophages was
      associated with rapid and transient tyrosine phosphorylation of the Cbl adaptor
      protein. Immunoprecipitated Cbl was complexed with several tyrosine
      phosphorylated proteins, the most prominent of which was a 38-kDa band identified
      as the CrkL adaptor protein. CrkL associated with tyrosine-phosphorylated Cbl and
      itself became tyrosine phosphorylated after Fc gammaRI cross-linking. SLP-76, a
      recently cloned Grb2-associated protein, was strongly tyrosine phosphorylated
      after Fc gammaRI stimulation and was associated with both Cbl and Grb2. Grb2 and
      Cbl binding to SLP-76 were inducible after Fc gammaRI stimulation of the
      macrophages. Nck was inducibly bound to Cbl after Fc gammaRI stimulation, whereas
      Grb2 was constitutively associated with it. Shc was also inducibly tyrosine
      phosphorylated and bound to Grb2 after Fc gammaRI stimulation of the macrophages.
      PP1, a specific inhibitor of Src kinases, inhibited the Fc gammaRI-induced
      respiratory burst, as well as the tyrosine phosphorylation of Cbl and its
      inducible association with CrkL. These results suggest a fundamental role for the
      tyrosine phosphorylation of Cbl, CrkL, SLP-76, and Shc and the association of Cbl
      with CrkL, SLP-76, and Nck in Fc gammaRI signaling in human macrophages.
      Experiments performed with PP1, the specific Src kinase inhibitor, demonstrate
      the first evidence that Cbl and the Cbl-Crkl interaction are downstream targets
      for myeloid Src kinases required for the activation of myeloid NADPH oxidase
      activity.

PMID- 10204584
TI  - A randomized controlled trial comparing plasma removal with white cell reduction
      to prevent reactions to platelets.
AB  - BACKGROUND: Recent data suggest that most reactions to platelets are caused by
      white cell (WBC)-derived cytokines that accumulate in the plasma portion of the
      component during storage. On the basis of this theory, the effectiveness of two
      interventions to prevent reactions, poststorage WBC reduction and plasma
      depletion, were compared. STUDY DESIGN: A multiple crossover design was used, in
      which platelet components for transfusion to a patient randomly were WBC reduced
      after storage, or the plasma supernatant was removed. Adults >17 years of age,
      with a hematologic disease requiring platelet transfusion support, were eligible
      for the study. Patients were assessed for signs and symptoms characteristic of a
      reaction during, immediately after, and 1 hour after transfusion. Reactions were
      graded as mild, moderate, or severe. Interleukin 6 levels were also measured in
      the transfused platelet components. RESULTS: There were 380 analyzable platelet
      transfusions to 30 patients. The frequency of reactions was 25.8 percent (48/186)
      in the transfusions of poststorage WBC-reduced platelets and 17.0 percent
      (33/194) in the transfusions of plasma-depleted platelets (p<0.008). The severity
      of the reaction was graded by the patient. Severe reactions occurred more
      frequently in connection with poststorage WBC-reduced platelets than with plasma
      depleted platelets: 33.4 percent (16/48) versus 18.2 percent (6/33), respectively
      (p = 0.048). Regression analysis identified interleukin 6 as the most significant
      of the evaluated factors in its correlation with the risk of reaction.
      CONCLUSION: Plasma removal is more effective than poststorage WBC reduction in
      preventing reactions, especially severe reactions to platelets.

PMID- 10204585
TI  - Elimination of cytokine production in stored platelet concentrate aliquots by
      photochemical treatment with psoralen plus ultraviolet A light.
AB  - BACKGROUND: Cytokines generated in platelet concentrates (PCs) during storage
      have been implicated as possible mediators of febrile nonhemolytic transfusion
      reactions. Two potential methods of white cell inactivation were compared for
      their ability to reduce cytokine synthesis in pooled random-donor PC aliquots:
      treatment with gamma-radiation and photochemical treatment (PCT) using psoralens
      and ultraviolet A light. STUDY DESIGN AND METHODS: ABO-matched PC aliquots were
      pooled and divided into separate aliquots. Aliquots (20 mL) were taken from each
      pool to serve as an untreated control and to undergo gamma-radiation. Aliquots
      were treated by using either gamma-radiation (2500 or 5000 cGy) or virucidal PCT.
      PCT with the psoralens 8-methoxypsoralen (8-MOP), aminomethyltrimethyl psoralen
      (AMT), and S-59 was investigated. PC aliquots were stored for 7 days and analyzed
      for levels of interleukin 8 by use of an enzyme-linked immunosorbent assay.
      Levels of DNA adduct formation were determined by using 3H-labeled psoralens.
      RESULTS: Levels of interleukin 8 in the untreated random-donor PC aliquots
      increased with increasing white cell counts, but they were not affected by
      pooling. The untreated control aliquots and the aliquots treated with gamma
      radiation had significant increases in levels of interleukin 8 after 5 to 7 days
      of storage (p<0.05). PCT with S-59 resulted in a significant reduction in
      cytokine synthesis (p<0.05). Day 5 to 7 levels of interleukin 8 did not differ
      significantly from Day 0 levels. Inhibition of interleukin 8 production by PCT
      increased with increasing levels of DNA modification (S-59 > AMT > 8-MOP).
      CONCLUSION: PCT that utilizes S-59 has been developed to inactivate potential
      viral and bacterial pathogens in PC aliquots while maintaining in vitro platelet
      function. These data demonstrate that PCT of aliquots of pooled PC aliquots
      before storage also prevents white cell cytokine synthesis during storage. PCT
      may therefore offer the potential for reducing cytokine-associated febrile
      nonhemolytic transfusion reactions.

PMID- 10204586
TI  - Virus reduction in the preparation of intravenous immune globulin: in vitro
      experiments.
AB  - BACKGROUND: While immune globulins for intravenous administration (IGIV) have an
      excellent record with respect to virus safety, concern regarding these
      preparations has been raised by reports of transmission of hepatitis C virus
      (HCV) to patients treated with IGIV and the presence of genetic material for HCV
      in IGIV preparations. STUDY DESIGN AND METHODS: This in vitro study evaluated the
      effectiveness of several manufacturing steps, including ethanol precipitation and
      pasteurization, in reducing HIV and model viruses including encephalomyocarditis
      (EMC) virus, pseudorabies virus (PRV), bovine viral diarrhea virus (BVDV),
      Sindbis virus, vaccinia virus, and vesicular stomatitis virus (VSV), as well as
      HCV RNA, in IGIV. RESULTS: Ethanol precipitation carried out after pasteurization
      resulted in virus reductions (log10) of >3.97 for HIV, 1.95 for EMC virus, >5.39
      for PRV, and 3.52 for BVDV. Pasteurization inactivated EMC virus by 4.52 log10
      and resulted in a log10 reduction of >6.54 for HIV, >5.39 for PRV, >6.64 for
      BVDV, >7.78 for Sindbis virus, >5.84 for vaccinia virus, and >6.99 for VSV. All
      viruses except EMC virus were reduced below the limit of detection within 6 hours
      of the beginning of pasteurization. Cohn processing of Fraction II + III paste
      and the 4.5-percent alcohol precipitation step prior to pasteurization provided
      additional virus removal. Studies using the polymerase chain reaction technique
      found that HCV RNA was detectable in the starting fraction of Cohn Fraction II
      paste, but not in the final IGIV preparation. CONCLUSION: These findings strongly
      support the viral safety of IGIV prepared by this method and show a significant
      added measure of virus safety associated with pasteurization of this preparation.

PMID- 10204587
TI  - Effect of recombinant human megakaryocyte growth and development factor coupled
      with polyethylene glycol on the platelet storage lesion.
AB  - BACKGROUND: Platelet production is regulated by a thrombopoietic growth factor
      (Mpl ligand). The receptor for this platelet growth factor (Mpl) is expressed on
      the platelet surface membrane. A recombinant thrombopoietic cytokine, recombinant
      human megakaryocyte growth and development factor coupled with polyethylene
      glycol (PEG-rHuMGDF), was added to apheresis platelets in vitro to determine
      whether Mpl ligand-receptor binding produced any beneficial or adverse effect on
      the development of the platelet storage lesion during 5 days of storage. STUDY
      DESIGN AND METHODS: This study was designed as a dose-response protocol to
      determine the effects of adding increasing concentrations of PEG-rHuMGDF (0.0
      [control], 2.5, 25, and 250 ng/mL) to apheresis platelets stored in two types of
      plastic storage containers. The increasing concentrations of PEG-rHuMGDF used
      simulated the theoretical peak plasma level attained in vivo, with an intravenous
      dose of 0, 0.1, 1.0 and 10 microg per kg of PEG-rHuMGDF. The platelets were
      stored with agitation at 20 to 24 degrees C for 5 days. A battery of in vitro
      assays was performed on storage Days 1 and 5, including pH, blood gases, platelet
      count, lactate dehydrogenase, mean platelet volume, glucose, lactate, osmotic
      recovery, morphology score, CD62P, and one-dimensional polyacrylamide gel
      electrophoresis analyses. RESULTS: Analysis of results on both Day 1 and Day 5
      showed no significant differences among any of the three PEG-rHuMGDF doses and
      the control group, for any in vitro assay. One-dimensional polyacrylamide gel
      electrophoresis showed no changes among the platelet protein patterns for the
      three PEG-rHuMGDF doses studied or the control. Storage-induced changes, however,
      did occur equally in all four groups of platelets over the 5 days of storage.
      CONCLUSION: The addition to stored apheresis platelets of up to 10 microg per kg
      of PEG-rHuMGDF (250 ng/mL), followed by 5 days of storage at standard conditions,
      does not appear to promote or retard development of the platelet storage lesion.

PMID- 10204588
TI  - Six filters for the removal of white cells from red cell concentrates, evaluated
      at 4 degrees C and/or at room temperature.
AB  - BACKGROUND: Six filters were tested for their ability to remove white cells from
      buffy coat-depleted red cell concentrates at various temperatures. STUDY DESIGN
      AND METHODS: Cellselect FR, BPF4, and Sepacell filters were tested at both room
      temperature (RT) and 4 degrees C. The Leucoflex filter was tested only at 4
      degrees C, while the Cellselect Optima Plus and Imugard filters were tested only
      at RT. Donor-dependent differences were excluded by pooling and subsequently
      dividing 9 red cell concentrates; 12 sets of experiments were performed. RESULTS:
      With all filters, red cell concentrates containing <5 x 10(6) white cells per
      unit were obtained. The lowest numbers of residual white cells were achieved with
      the Leucoflex (at 4 degrees C, 0.15 +/- 0.11 x 10(6), the Sepacell (at 4 degrees
      C, 0.23 +/- 0.14 x 10(6), the Imugard (at RT, 0.24 +/- 0.14 x 10(6), and the BPF4
      (at 4 degrees C, 0.25 +/- 0.24 x 10(6); differences not significant). With the
      Cellselect FR, filtration at 4 degrees C resulted in 0.86 +/- 0.37 x 10(6) white
      cells per unit, a level not significantly different from that obtained with the
      BPF4 and Sepacell filters at RT (1.16 +/- 0.43 x 10(6) and 0.80 +/- 0.36 x 10(6)
      white cells, respectively). Filtration at RT with the Cellselect FR and
      Cellselect Optima Plus resulted in red cell concentrates with 1.79 +/- 0.69 x
      10(6) and 2.29 +/- 0.69 x 10(6) white cells, respectively (p<0.01). CONCLUSION:
      All filters conformed to the current standards for white cell reduction; the
      process was less efficient at RT than at 4 degrees C. For routine application,
      the composition of the red cell concentrate, the temperature, and logistic
      preferences should be taken into account in the final choice of filter; before
      implementation, the chosen filter must be validated under routine conditions.

PMID- 10204589
TI  - Greater increase in cytokine concentration after salvage with filtered whole
      blood than with washed red cells, but no difference in postoperative hemoglobin
      recovery.
AB  - BACKGROUND: Inflammatory mediators are released in association with
      intraoperative and postoperative salvage of blood. Whether these mediators
      (cytokines) participate in the modulation of erythropoiesis or not has been
      investigated. STUDY DESIGN AND METHODS: Twenty-seven patients who were to undergo
      total knee replacement surgery were randomly assigned to postoperative blood
      salvage with either filtered whole blood or washed red cells. Patients with
      postoperative blood loss <400 mL were considered a control group. The control
      group did not receive any transfusions. Plasma concentrations of the
      anaphylatoxin C3a, the C5b-9 terminal complement complex, and the cytokines
      interleukins 6 and 8, hemoglobin, reticulocytes, and red cell volume fraction in
      the patients were repeatedly analyzed before and after surgery. RESULTS:
      Significantly increased concentrations of interleukin 6 appeared in all three
      groups, which was interpreted as a response to the surgical trauma. The increase
      was significantly greater in the group that received filtered whole blood after
      return of shed blood. The recovery of hemoglobin levels did not differ in the
      groups. CONCLUSION: The transfusion of filtered whole blood leads to the
      formation of interleukin 6 in the circulation, but postoperative hemoglobin
      recovery was similar in all groups.

PMID- 10204590
TI  - Alteration of red cell aggregability and shape during blood storage.
AB  - BACKGROUND: Storage of blood units (for 35-42 days, depending on the preservative
      solution) has been reported to induce changes (e.g., reduction of sialic acid
      level) in red cells that are expected to alter their aggregability. STUDY DESIGN
      AND METHODS: The aggregability of stored red cells was monitored in their
      autologous plasma and compared to that obtained with washed cells in dextran
      containing buffer throughout the storage period. Red cell aggregability was
      determined by using a computerized image analyzer of cell flow properties.
      RESULTS: Blood storage induced changes in red cells that are associated with
      continuous increase of their aggregability. At the same time, blood storage was
      associated with a reduction in the level of plasma fibrinogen, the major
      aggregating agent in plasma. Accordingly, the increased red cell aggregability
      was observed in red cells stored in dextran-containing buffer, but not in red
      cells stored in autologous plasma. CONCLUSION: Because blood transfusion is
      routinely given to patients with normal or high fibrinogen level, the transfusion
      of stored red cells has the potential to induce increased aggregation in vivo,
      depending on the storage period. This should be taken into account when blood
      transfusion is considered, particularly for patients with microcirculatory
      disorders.

PMID- 10204591
TI  - Frequency of immediate adverse effects associated with therapeutic apheresis.
AB  - BACKGROUND: Therapeutic apheresis was found to be reasonably safe in prior
      studies using instruments that are now largely obsolete. The incidence of adverse
      effects with current instruments and techniques has not been assessed in a large
      multicenter study. STUDY DESIGN AND METHODS: A survey was conducted in 1995 using
      a uniform questionnaire that asked about 32 specific events but excluded
      transient paresthesia and mild vasovagal events. Eighteen centers returned 3429
      responses concerning 125 to 500 therapeutic apheresis procedures per center.
      RESULTS: Two hundred forty-two adverse events were reported in 163 procedures
      (4.75% of all procedures; 6.87% of first-time procedures and 4.28% of repeat
      procedures). The numbers (incidence) of selected specific events were transfusion
      reaction, 56 (51 in plasma exchange [PE] with plasma replacement) (1.6%); citrate
      related nausea and/or vomiting, 41 (1.2%); systolic blood pressure <80 mmHg, 34
      (1.0%); vasovagal nausea and/or vomiting, 17 (0.5%); pallor and/or diaphoresis,
      16 (0.5%); pulse >120, 14 (0.4%); respiratory distress, 9 (0.3%); tetany or
      seizure, 9 (0.2%); and chills or rigors, 6 (0.2%). Rates for other specific
      events were < or =0.1 percent. Vasovagal phenomena were more frequent in
      procedures done in neurologic patients than in those done in hematology or
      oncology patients (p = 0.011) or renal or rheumatic patients (p = 0.038).
      Procedure-specific rates were red cell exchange, 8 (10.26%) of 78; PE (plasma),
      89 (7.81 %) of 1140; PE (no plasma), 42 (3.35%) of 1255; leukapheresis, 4 (5.71%)
      of 70; plateletpheresis, 0 of 18; and autologous peripheral blood progenitor cell
      collection, 11 (1.66%) of 664. Three deaths were reported; all were attributed to
      primary disease. CONCLUSION: Therapeutic apheresis procedures are relatively
      safe, with a 4.75-percent overall incidence of mostly reversible adverse effects.
      Among the most commonly performed procedures, the risk is higher for blood
      component exchanges, especially if allogeneic red cell or plasma transfusion
      occurs, and lower for peripheral blood progenitor cell collection.

PMID- 10204592
TI  - Hydroxyethyl starch reduces the chemotaxis of white cells through endothelial
      cell monolayers.
AB  - BACKGROUND: Polymorphonuclear leukocytes (PMNs) play a tremendous role during
      inflammatory processes. PMNs have to pass a monolayer of endothelial cells to
      migrate into the extravascular space. Hydroxyethyl starch (HES) is frequently
      used as a volume expander in critically ill patients. STUDY DESIGN AND METHODS:
      The aim of this study was to investigate whether HES influences the chemotaxis of
      PMNs through endothelial cell monolayers by using a test system that allows the
      simultaneous treatment of both cell types. Human umbilical endothelial cells were
      cultured on microporous membrane filters. PMNs were isolated and PMN chemotaxis
      was studied. RESULTS: The number of untreated PMNs that migrated through
      untreated endothelial cell monolayers in response to a chemoattractant was used
      as a control and set as 100 percent. In clinically relevant concentrations, HES
      was able to significantly decrease PMN chemotaxis through endothelial cell
      monolayers, showing a dose-dependent effect (0.1 mg/mL: 99.6 +/- 10.9%, p = NS
      compared to control; 1 mg/mL: 82.4 +/- 8.3%, p<0.05 compared to control; 10
      mg/mL: 62.9 +/- 11.7%, p<0.05). In this assay, both cell types (PMNs and
      endothelial cells in the monolayer) were treated simultaneously, which simulated
      the clinical situation after an intravenous injection of HES. The treatment of
      one cell type, PMNs (89.6 +/- 8.8%, p<0.05) or endothelial cells in the monolayer
      (76.2 +/- 9.4%, p<0.05), suggests that the influence on endothelial cells is
      greater. CONCLUSION: HES is able to significantly reduce the chemotaxis of PMNs
      through endothelial cell monolayers. The possible clinical consequence of a
      moderate reduction in endothelium-mediated PMN chemotaxis in critically ill
      patients remains to be evaluated.

PMID- 10204593
TI  - Revisiting the issue: can the reading for serologic reactivity following 37
      degrees C incubation be omitted?
AB  - BACKGROUND: Omitting the 37 degrees C reading from screening tests for unexpected
      antibodies results in failure to detect some Rh, K, and Jk agglutinins of
      potential significance (wanted positives). However, this measure avoids unwanted
      positive tests due to cold agglutinins. STUDY DESIGN AND METHODS: Using data from
      prior publications, actual risk calculations (ARCs) were made to predict the risk
      of eliminating the 37 degrees C reading, pretransfusion direct antiglobulin test
      (DAT), and routine indirect antiglobulin crossmatch (IAT-XM). ARCs used the
      equation: wanted positives missed x 0.34 (or 0.80) x 5 x percent antigen
      positive, where 0.34 = percent of patients transfused (ARCs for 37 degrees C
      reading and DAT); 0.80 = percent of crossmatched patients transfused (ARCs for
      IAT-XM); 5 = average number of units transfused. Following elimination of the 37
      degrees C reading, the impact of this change on patient care was monitored.
      Antibody detection and identification data and transfusion reaction reports for 6
      months after the change were reviewed. Recently transfused patients with new
      antibodies were evaluated for immune hemolysis by review of clinical and
      laboratory data. The findings were compared with those from the same dates of the
      preceding year. RESULTS: The risk of transfusing incompatible blood by
      eliminating the DAT, IAT-XM, and 37 degrees C reading is approximately 1:13,000,
      1:2,000, and 1:2,400 units transfused, respectively. The cumulative risk from
      eliminating all three tests is approximately. 1 :1,000 units. With respect to the
      37 degrees C reading, there were no differences between the pre-change and post
      change study periods in the incidence of reported transfusion reactions or cases
      of immune hemolysis associated with newly formed antibodies. However, unwanted
      positive tests decreased from 162 to 61 following elimination of the 37 degrees C
      reading. This represents a decrease of 20 percent in the number of samples
      requiring antibody identification annually. CONCLUSIONS: Eliminating the 37
      degrees C reading from pretransfusion antibody screening tests imposes less risk
      than omitting the routine IAT-XM, and it avoids the time and costs of evaluating
      unwanted positive tests, thus reducing expenditures and delays in patient care.

PMID- 10204594
TI  - Evaluation of the gel system for ABO grouping and D typing.
AB  - BACKGROUND: The gel agglutination assay has been approved by the Food and Drug
      Administration as an alternative to the tube assay for the detection of red cell
      antibodies. It has also been approved recently by the Food and Drug
      Administration for ABO blood grouping and D typing. STUDY DESIGN AND METHODS:
      Tube and gel agglutination assays were compared for ABO grouping and D typing of
      100 donor and 100 patient specimens. ABO grouping of 14 specimens of known ABO
      groups and D typing of 10 specimens with weak D were also compared. When antigen
      typing or isohemagglutinin results differed, gel testing was repeated by the use
      of modified incubation times, reagent or specimen volumes, and red cell
      concentrations. RESULTS: ABO grouping and D typing in all patient and donor
      specimens concurred. B isohemagglutinins were not detected in seven group A
      specimens. Six of seven discrepancies were resolved when gel tests were incubated
      at room temperature with increased serum or plasma volume. Weak D was detected in
      all 10 specimens tested by both assays. When weak A and/or B were tested with
      monoclonal antibody reagents, the correct phenotypes were identified in 9
      specimens by gel assay and in 10 by tube assay. Using human antisera, 6 specimens
      were correctly phenotyped by gel assay and 7 by tube assay. CONCLUSION: The gel
      assay performed as well as the tube assay in detection of A, B, and D, but the
      tube assay was slightly better at detecting B isohemagglutinins. The gel assay
      can be used in place of the tube assay for ABO blood grouping and D typing.

PMID- 10204595
TI  - Ceftizoxime-induced hemolysis due to immune complexes: case report and
      determination of the epitope responsible for immune complex-mediated hemolysis.
AB  - BACKGROUND: Several occurrences of immune complex-mediated, cephalosporin-induced
      intravascular hemolysis have been reported. This report describes the first case
      of hemolytic anemia caused by an immune-complex mechanism associated with
      ceftizoxime and delineates the epitope responsible for hemolysis. CASE REPORT:
      The patient's serum was tested for antibody that reacted with five penicillins
      and 30 cephems (all types of cephalosporins) by using protocols to detect drug
      adsorption and immune-complex mechanisms. The patient's antibody that formed
      immune complexes with ceftizoxime reacted with 10 of 30 cephems. These 10 drugs
      were classified as oxime-type cephalosporins, which have a common structural
      formula consisting of [(Z)-2-(2-amino-4-thiazolyl)-2-methoxyiminoacetoamido] at
      the C7 position on 7-aminocephalosporinic acid with or without substitution at
      the C3 position. CONCLUSION: The patient's antibody recognized a common structure
      in 10 oxime-type cephalosporins, and immune complexes formed by the antibody
      specifically or nonspecifically bound to red cell membranes. Therefore, when
      intermittent antibiotic therapy is required, as in this case, care should be
      taken in antibiotic selection to avoid drug-induced hemolytic anemia. In
      addition, when this type of hemolysis is observed, tests for antibody that reacts
      by adsorption and immune-complex mechanisms should be performed against
      penicillins and cephems to select antibiotics not showing a cross-reaction.

PMID- 10204596
TI  - Trypanosoma cruzi in a low- to moderate-risk blood donor population:
      seroprevalence and possible congenital transmission.
AB  - BACKGROUND: Several recent studies documented the seroprevalence of Trypanosoma
      cruzi in blood donors at high risk for infection, but little information is
      available regarding donors with lower levels of risk. Thus, the present study was
      designed to measure the seroprevalence of T. cruzi in a donor population with a
      low to moderate risk for infection. STUDY DESIGN AND METHODS: During a 10-month
      period, donations from all allogeneic blood donors in the American Red Cross
      Southwest Region were tested for T. cruzi antibodies by enzyme immunoassay, and
      results were confirmed by radioimmunoprecipitation. Confirmed-seropositive donors
      were counseled and lookback investigations were initiated for those who were
      repeat donors. RESULTS: A total of 100,089 donations were tested: 150 were
      repeatably reactive, and 3 (0.003%) were confirmed as positive for T.
      cruziantibodies. All three seropositive donors were from the Waco, TX, area,
      where the estimated seroprevalence rate was 1 in 7700. Two of these three donors
      reported no risk factors; both were born in the United States and had not
      traveled to an endemic area. Both had extensive familial histories of cardiac
      disease and complications. CONCLUSION: Blood donors seropositive for T. cruzi are
      present in populations with low to moderate risk, albeit at lower rates. The
      presence of seropositive blood donors without the usual identifiable risk factors
      argues against the use of a geographic screening question and also suggests that
      other routes of transmission, including the congenital route, should be
      considered in efforts to increase blood safety.

PMID- 10204597
TI  - A case-controlled multicenter study of vasovagal reactions in blood donors:
      influence of sex, age, donation status, weight, blood pressure, and pulse.
AB  - BACKGROUND: Vasovagal reactions occur in a small, but significant number of blood
      donors. These reactions may decrease return donation and disrupt blood collection
      activities. The purpose of this study was to define the contributory role of sex,
      age, weight, blood pressure, and pulse in vasovagal reactions with syncope in
      blood donors. STUDY DESIGN AND METHODS: A retrospective case-control study
      involved 1890 blood donors with syncope from three large United States blood
      centers during 1994 and 1995. Case controls and random population controls were
      used in a logistic regression analysis to determine the significance of
      individual variables to syncopal reactions. RESULTS: Female donors, young donors,
      first-time donors, low-weight donors, and donors with low predonation blood
      pressure had higher absolute donation reaction rates than other donors. When each
      variable was adjusted for other variables by regression analysis, age, weight,
      and donation status (first-time or repeat donor) were significant (p<0.0001), and
      sex, predonation blood pressure, and predonation pulse were not. The most
      important variables, in descending order, were age, weight, and donation status
      (first-time or repeat donor). CONCLUSIONS: Donation-related vasovagal syncopal
      reactions are a multifactorial process determined largely by age, weight, and
      first-time donor status.

PMID- 10204598
TI  - Platelet growth factors: potential impact on transfusion medicine.

PMID- 10204599
TI  - Effect of transfusion on lipid peroxidation products in the plasma of thalassemic
      patients.

PMID- 10204600
TI  - Peripheral blood progenitor cell collections in children.

PMID- 10204601
TI  - Failure of third-generation recombinant immunoblot assay to detect hepatitis C
      virus core antibodies.

PMID- 10204602
TI  - Hepatitis G virus or hepatitis GB virus type C infection in thalassemic patients.

PMID- 10204603
TI  - Identification of connexins in human oral mucosa and therapeutic effect of
      irsogladine maleate on aphthous stomatitis.
AB  - We identified connexins 26 and 32 in human oral mucosa. The presence of the
      connexins indicates the presence of gap junctions in this tissue. However,
      immunofluorescence study found no significant differences in the expression of
      the connexins between patients with aphthons stomatitis and controls. Irsogladine
      maleate, which reinforces gap junctional intercellular communication in vitro,
      was effective for the treatment of transient and relapsing aphthous stomatitis,
      as well as symptomatic and drug-induced aphthous stomatitis. It was also useful
      for prevention of episodes of relapsing aphthous stomatitis, with daily
      administration preverting recurrence of stomatitis for more than 4 years one
      patient. These findings suggest that irsogladine maleate accelerates the wound
      healing process in oral mucosa by reinforcing gap junctional intercellular
      communication among oral mucosal cells; and that it is useful for the treatment
      and prevention of aphthous stomatitis.

PMID- 10204605
TI  - Higher frequencies of numerical aberrations of chromosome 17 in primary gastric
      cancers are associated with lymph node metastasis.
AB  - We investigated the correlation between the frequency of numerical aberrations of
      chromosome 17 and clinicopathological features of gastric cancer. The copy number
      of chromosome 17 was examined with fluorescence in-situ hybridization (FISH) in
      frozen specimens from 100 primary gastric cancers. Chromosomal numerical
      aberrations were diagnosed as chromosomal loss (single signal) or gain (triple or
      more signals), in each cell. The frequency of numerical aberrations of chromosome
      17 correlated significantly with the depth of invasion (P < 0.01), lymph node
      metastasis (P < 0.0001), lymphatic invasion (P < 0.001), and venous invasion (P <
      0.01). Numerical aberrations of chromosome 17 were associated with lymph node
      metastasis in 32 early gastric cancers. Multiple regression analysis identified
      the depth of invasion and numerical aberrations of chromosome 17 as independent
      significant determinants of lymph node metastasis. Our findings suggest that
      alterations in chromosome 17 may be linked with tumor progression in primary
      gastric cancer. Our results also indicate that numerical aberrations of
      chromosome 17 detected by FISH provide important information about the malignant
      potential (in particular, lymph node metastasis) of primary gastric cancer.

PMID- 10204604
TI  - Evaluation of a new immunochromatographic test for Helicobacter pylori IgG
      antibodies in elderly symptomatic patients.
AB  - AIM: To determine the diagnostic value of a new serum and whole blood serological
      IgG antibody test, FlexPack HP, for the diagnosis of Helicobacter pylori in
      elderly symptomatic patients. METHODS: 94 consecutive symptomatic patients who
      underwent upper endoscopy were studied (mean age, 62.6 years). On endoscopy, the
      presence of H. pylori infection was examined by biopsies from gastric antrum and
      body for rapid urease test and histologic examination. Blood was drawn prior to
      endoscopy and both blood and serum were immediately analyzed for human IgG
      antibodies to H. pylori by a new commercially available qualitative
      immunochromatographic method, FlexPack HP. This test incorporates high-molecular
      weight cell-associated proteins (HM-CAP), which are highly specific for H. pylori
      IgG antibodies. RESULTS: Overall agreement for FlexPack HP whole blood vs
      FlexPack HP serum was 100%, and agreement with biopsy results was 71%. The gold
      standard (detection of H. pylori by histology or urease test) identified H.
      pylori in 61 patients (65%). Complete agreement was observed between the gold
      standard test and the serology kit in 72% (68/94) of sera (51 positive and 17
      negative). Disagreement was found in sera of 26 patients; 16 sera were negative
      by the gold standard and positive by FlexPack HP and 10 patients were found
      negative by serology. The sensitivity of FlexPack HP was 84% and the specificity
      52% when compared with the gold standard. CONCLUSIONS: FlexPack HP serum and
      whole blood test is a simple and reliable method for the detection of H. pylori
      antibodies, with 100% agreement between the serum and blood results. In the
      elderly symptomatic patients the sensitivity of FlexPack HP was similar to that
      of other serologic tests, but the specificity was relatively low, limiting its
      use in this population.

PMID- 10204606
TI  - Clinicopathological study of background gastric mucosa during long-term
      conservative maintenance therapy for intractable peptic ulcer.
AB  - We studied the background gastric mucosa in eight patients with intractable
      peptic ulcer in whom gastric cancer developed during more than 4 years'
      administration of histamine (H)2-receptor antagonists (H2-RAs), and in two
      patients with intractable gastric ulcer without gastric cancer in whom H2-RAs
      were administered for 4 years. As controls, we studied background mucosa in seven
      patients with combined gastroduoderal ulcers not treated with H2-RAs. The cancers
      were differentiated adenocarcinomas in all eight patients. The characteristic
      features of these patients and of the two patients with intractable gastric ulcer
      were: expansion of the generative cell zone, poor differentiation of the goblet
      cells, mild cellular atypia, and abnormal branching and anastomosis of glands, as
      well as wide areas of incomplete-type intestinal metaplasia. The sites of the
      differentiated adenocarcinomas were classified by mucin histochemistry as
      intestinal-type mucosa in all patients. A special type of incomplete intestinal
      metaplasia, of the intestinal type and which retained gastric-type properties,
      was present in some areas, and p53-positive cells were observed in some areas. In
      patients with intractable gastric ulcer in whom the background gastric mucosa had
      been exposed to more than 4 years of H2-RA treatment, it was considered possible
      that the preconditions for cancerous lesions were present.

PMID- 10204607
TI  - Ultrastructure of rat duodenal myenteric plexus revealed by quick-freezing and
      deep-etching method.
AB  - A quick-freezing and deep-etching (QF-DE) method was employed with whole-mount
      strips of rat duodenal muscle walls to exhibit the cytoskeletons of the myenteric
      plexus. Nerve fibers in the myenteric plexus, which contained fewer
      neurofilaments than other types of neurons examined, had many varicosed contours,
      and were bundled by enteroglial cells. Cytoskeleton arrays were rarely observed
      in the varicosed regions, where synaptic vesicles were often seen, although other
      nerve regions contained many neurofilaments running almost in parallel with the
      nerve fiber bundle. Enteroglial cells had short cytoskeletons predominantly
      across the cytoplasm, becoming thinner the around varicosed regions of the nerve
      bundles. Such enteroglial extruded areas were often in close association with
      neighboring nerve fibers, indicating intercommunications between the nerve
      fibers. In distal parts of enteric nerve processes, there were numerous synaptic
      vesicles, but few neurofilaments. Smooth muscle cells were closely associated
      with the enteric nerve processes. Fine network structures, responsible for the
      extracellular matrix, were present between the smooth muscle cells and the
      enteric nerve processes. These specific structures of the myenteric plexus could
      be important for signalling or for the transportation of neurotransmitters
      involved in gut motility.

PMID- 10204608
TI  - Screening for gastroenterological malignancies in new and maintenance dialysis
      patients.
AB  - To screen for gastroenterological malignancies in dialysis patients, we used the
      fecal occult blood test, examined the upper and lower gastrointestinal tract, and
      used abdominal ultrasonography in 178 patients starting dialysis (171 on
      hemodialysis and 7 on continuous ambulatory peritoneal dialysis (CAPD)) and 34
      patients on maintenance dialysis (27 on hemodialysis and 7 on CAPD). Screening
      disclosed ten cancers (one esophageal cancer, three gastric cancers, four
      colorectal cancers, and two hepatocellular carcinomas) in 9 of the patients
      starting dialysis. Six cancers (one esophageal, three gastric, one colorectal,
      and one renal) were detected in 5 of the patients on maintenance dialysis. Since
      an increased incidence of malignancy has been reported in dialysis patients,
      gastroenterological screening appears to be worthwhile.

PMID- 10204609
TI  - Laboratory diagnosis of toxigenic Clostridium difficile by polymerase chain
      reaction: presence of toxin genes and their stable expression in toxigenic
      isolates from Japanese individuals.
AB  - Clostridium difficile causes pseudomembranous colitis and antibiotic-associated
      diarrhea. The definitive diagnosis of C. difficile infection is finally
      accomplished by the isolation of toxigenic C. difficile. However, only a small
      number of Japanese clinical laboratories are able to reach a definitive diagnosis
      of C. difficile infection, probably because simple reliable assays for toxins in
      the isolates are not available. In this study, we examined the compatibility of a
      polymerase chain reaction (PCR) assay and tissue culture assay to identify
      toxigenic C. difficile, in toxigenic and nontoxigenic C. difficile isolates from
      Japanese patients and healthy carriers. The specificity of PCR primers was
      demonstrated by restriction endonuclease digestion and seminested PCR in C.
      difficile VPI 10463 strain. No PCR product was amplified in the eight other
      clostridial species used to check the specificity of the PCR assay. The detection
      limit was 10(3) cells. Both toxin A and toxin B genes (the genes encoding the
      major virulence factors of C. difficile) were detected in 58 toxigenic C.
      difficile isolates, which showed a wide range of cytotoxic activity in tissue
      culture assays. Neither of the toxin genes was carried by 40 nontoxigenic strains
      of C. difficile. The results of this study strongly suggest that a definitive
      diagnosis of C. difficile infection can be accomplished by PCR detection of the
      toxin genes rather than by tissue culture assay of isolates.

PMID- 10204610
TI  - Phospholipid turnover in the inflamed intestinal mucosa: arachidonic acid-rich
      phosphatidyl/plasmenyl-ethanolamine in the mucosa in inflammatory bowel disease.
AB  - Cytosolic phospholipase A2 (PLase A2) is activated by low Ca2+ concentrations and
      translocates from the cytosol to the cell membrane, releasing arachidonic acid;
      the arachidonic acid cascade then leads to the production of many inflammatory
      mediators. The aim of this study, accordingly, was to investigate the role of
      phospholipid metabolism in the intestinal mucosa in inflammatory bowel disease
      (IBD). Surgically resected specimens from patients with Crohn's disease (CD),
      ulcerative colitis (UC), and colrectal cancer (non-cancerous tissue; as a
      control) were submitted to phospholipid analysis and a PLase A2 assay, which
      measures the degradation of endogenous mucosal phospholipids. A high percentage
      of plasmenylethanolamine (plas.E) was detected in the glycerophospholipid
      fraction of CD mucosa. The arachidonic acid content of the
      phosphatidylethanolamine plus plas.E subfraction was higher in inflamed than in
      intact mucosa in CD. PLaseA2 activity, resulting in lysophosphatidyl ethanolamine
      production, was detected only in inflamed mucosa from CD and UC patients, but not
      in normal mucosa from controls. PLaseA2 activity was highest in moderately
      inflamed mucosa adjacent to a severely ulcerated area. The PLaseA2 that reacts
      with endogenous phosphatidylcholine (PC) to form lysoPC was found irrespective of
      the presence of inflammation. The PLaseA2 that reacts with ethanolamine
      containing phospholipids is more closely related to inflammation than other
      PLaseA2 isoenzymes in IBD mucosa.

PMID- 10204611
TI  - Colonization of microflora in mice: mucosal defense against luminal bacteria.
AB  - To investigate the pathogenesis of inflammatory bowel disease, it is critical to
      develop a system that uses simple and reproducible models for analyzing the
      "normal" mucosal defense mechanism. In the present study, germ-free mice were
      conventionalized by the oral administration of microorganisms prepared from the
      feces of genetically identical mice. Histological assessment and mucin
      characterization of small intestine and colon were then carried out. Histological
      findings in the gut were site-dependent and clearly time-dependent. Acute
      inflammation was most evident in the cecum. The cecal mucosa exhibited
      hyperplastic changes in epithelial cells, infiltration of polymorphonuclear
      cells, crypt abscesses, and epithelial projections on the epithelial surface 7
      days after conventionalization. Some of the changes were similar to those seen in
      human ulcerative colitis. The histological findings in the conventionalized mice
      were comparable to those in specific pathogen-free mice after 28 days. Mucin
      histochemistry revealed that bacterial colonization altered the number of rectal
      goblet cells and the mucin composition in a time-dependent fashion. Although this
      model shares only some characteristics of human inflammatory bowel disease, it is
      unique in demonstrating the acquisition of mucosal defense. Understanding of this
      process is critical for the elucidation of inflammatory bowel disease
      pathogenesis.

PMID- 10204612
TI  - High frequency of antigliadin antibodies and absence of antireticulin and
      antiendomysium antibodies in patients with ulcerative colitis.
AB  - Several authors have described an association between celiac disease (CD) and
      ulcerative colitis (UC), but this has not yet been established. The aim of our
      study was to examine the frequency of antigliadin antibodies (AGA), antireticulin
      antibodies (ARA) and antiendomysium (AEM) antibodies in the sera of patients with
      UC (n = 50), and to evaluate their correlation with clinical variables. Sixteen
      patients with irritable bowel syndrome (IBS) and 37 healthy individuals served as
      controls. An enzyme-linked immunosorbent assay was used for the detection of IgA-
      and IgG-type AGA. IgG-type ARA were determined by an indirect immunofluorescence
      assay (IIF) using rat kidney, liver, and stomach as antigen substrates. IgA-type
      AEM antibodies were measured by IIF, using cryostat sections from human umbilical
      cord. Seventeen of the 50 patients with UC (34%) were positive for IgA- or/and
      IgG-type AGA. There was no correlation between the presence of AGA and the
      duration or extent of the disease, or disease activity. However, 5 patients with
      both IgA- and IgG-types of AGA had extensive colitis. Only 2 controls (4%) were
      positive for IgG-AGA. ARA and AEM were not detected in any individuals studied.
      Since the ARA and AEM test results were negative, we conclude that none of the UC
      patients in this series had CD.

PMID- 10204613
TI  - Mucosal proinflammatory cytokine production correlates with endoscopic activity
      of ulcerative colitis.
AB  - Proinflammatory cytokines are believed to be involved in the pathogenesis of
      ulcerative colitis (UC). The aim of this study was to clarify the profiles of
      proinflammatory cytokine production in patients with UC in terms of disease
      intractability, endoscopic findings, and host response to lipopolysaccharide
      (LPS) stimulation. Colonic mucosal tissues were obtained from patients with
      active UC (n = 15, including 4 patients with intractable disease) and inactive UC
      (n = 7), non-inflammatory bowel disease (IBD) colitis (n = 11), and controls (n =
      20). Organ culture was performed, and the amounts of four cytokines (described
      below) in the culture media were determined by enzyme-linked immunosorbent assay
      (ELISA). LPS stimulation enhanced interleukin (IL)-1beta, IL-8, and IL-6
      production in colonic specimens from all groups, but enhanced tumor necrosis
      factor (TNF)-alpha production only in active UC specimens. Levels of IL-6, IL-8,
      and TNF-alpha were significantly higher in active UC than in non-IBD colitis, and
      the production of all three of these cytokines was correlated to the endoscopic
      grade of inflammation. The production of these cytokines was also significantly
      higher in patients with intractable disease receiving corticosteroids than in
      patients with non-intractable disease receiving corticosteroids. These results
      suggest that enhanced production of mucosal proinflammatory cytokines may be
      implicated in the pathogenesis of UC.

PMID- 10204614
TI  - Effects of "body compression" on parameters related to ascites formation:
      therapeutic trial in cirrhotic patients.
AB  - Decreased effective circulating blood volume is an important factor in ascites
      formation in liver cirrhosis. We designed a "body compression" apparatus as a
      means to restore effective blood volume and investigated its effectiveness in
      reducing ascites formation in cirrhotics in terms of its effect on parameters of
      ascites formation noted below. The subjects, eight cirrhotics with ascites and
      eight cirrhotics without ascites were given spironolactone (50-75 mg/day) and
      furosemide (40-80 mg/day) while they received a diet containing 85 mEq of sodium
      per day. All four limbs and the lower abdomen were compressed with constant
      pressure [height (cm) divided by 13.6 mmHg] once, for 3h, using stroke
      rehabilitation splints, while patients lay supine. In cirrhotics both with and
      without ascites, urine volume, urinary sodium excretion, and creatinine clearance
      during the body compression were greater than values during control (non
      compression) periods (urine volume, means 285 vs 169 ml/3h; P < 0.001, urinary
      sodium excretion 15.8 vs 9.5 mEq/3h; p < 0.001, creatinine clearance 74 vs 59
      ml/min, P < 0.001, respectively). The increased basal plasma renin activity,
      angiotensin II, aldosterone, and norepinephrine levels in all cirrhotics were
      significantly decreased by the body compression. In another group of six
      cirrhotics who received no diuretics or albumin, repeat body compression
      alleviated ascites in three with well preserved renal function, but was
      ineffective in three with markedly impaired renal function. These results suggest
      that the improvement in renal function brought about by the body compression is
      attributable to an increase in effective circulating blood volume. This maneuver
      may be a useful complementary therapy in patients with cirrhotic ascites with
      well preserved renal function.

PMID- 10204615
TI  - Telomerase reverse transcriptase mRNA expression and telomerase activity in
      hepatocellular carcinoma.
AB  - Human telomerase reverse transcriptase (hTERT) has been identified as the
      catalytic subunit of human telomerase. To clarify the clinical significance of
      hTERT mRNA in hepatocellular carcinoma (HCC), we investigated the relationship
      between telomerase activity and hTERT mRNA in human HCC and non-HCC tissues. The
      hTERT mRNA was detected in 17 (89.47%) of 19 livers with HCC and in 4 (21.05%) of
      19 noncancerous tissues from these livers. Telomerase activity was detected in 17
      of the 19 tumor tissues (89.47%) and in 4 of the 19 nontumor tissues (21.05%).
      The hTERT mRNA was detected in all tissues that were telomerase-positive and it
      was undetected in all tissues that were telomerase-negative. The correlation
      between the expression of hTERT mRNA and human telomerase activity in this study
      indicates that hTERT mRNA could be useful to diagnose cancer. Also, as telomerase
      production may be under the control of hTERT mRNA, the possibility is great that
      noncancerous liver tissue with chronic liver diseases acquires HCC when the hTERT
      mRNA is positive.

PMID- 10204616
TI  - Clinical usefulness of conjugated bilirubin levels in patients with acute liver
      diseases.
AB  - We used a specific method to measure conjugated bilirubin levels in patients with
      acute liver diseases to examine its clinical usefulness. Conjugated and total
      bilirubin levels were measured in 102 samples obtained from six patients with
      acute liver diseases (three with fulminant hepatic failure, one with acute severe
      hepatitis and two with acute hepatitis; see text for criteria). Total and
      conjugated bilirubin levels were measured with Iatro T (total)-Bil and D (direct)
      Bil kits (Iatron Laboratories Tokyo, Japan) and with conventional Nescauto
      T(total)-Bil and D(direct)-Bil VE kits (Nippor Shoji, Osaka, Japan). The Iatro D
      Bil kit measures conjugated bilirubin correctly, while the Nescauto D-Bil VE kit
      measures some nonconjugated bilirubin and delta bilirubin as well as conjugated
      bilirubin. Total bilirubin levels determined by the two methods showed good
      correlation. The conjugated bilirubin level measured with the Iatro D-Bil kit was
      strongly correlated with the direct bilirubin level measured with the Nescauto D
      Bil VE kit, but there was no correlation between the conjugated-to-total
      bilirubin ratio and the direct-to-total bilirubin ratio. When we examined the
      changes in bilirubin levels in our patients with respect to outcome, we found
      that the two patients in whom the ratio of conjugated-to-total bilirubin exceeded
      0.3 died, while all four patients in whom the ratio remained below 0.3 survived.
      The ratio of direct-to-total bilirubin was unrelated to outcome. The conjugated
      bilirubin level measured with the Iatro kits was therefore considered useful for
      the diagnosis and follow-up of acute liver diseases.

PMID- 10204618
TI  - Influence of histological inflammatory activity on regenerative capacity of liver
      after percutaneous transhepatic portal vein embolization.
AB  - Percutaneous transhepatic portal vein embolization (PTPE) produces regenerative
      hypertrophy in the nonembolized part of the liver, but the regenerative capacity
      after PTPE in patients with chronic hepatitis is unknown. We studied 34 patients
      with hepatocellular carcinoma and chronic hepatitis who underwent PTPE at the
      right portal vein. Hepatic lobular volumes were calculated by computed tomography
      before and 2 weeks after PTPE. The increase in left lobular volume was analyzed
      using a stepwise multiple regression method incorporating 11 factors: age; portal
      venous pressure; proportional volume of the right lobe; indocyanine green
      retention test; platelet count; serum levels of aspartate transaminase, alanine
      transaminase, total bilirubin, and albumin; and histological inflammatory grade
      and stage of fibrosis, according to the criteria of the International Association
      for the Study of the Liver recommended at their 1994 meeting. The median volume
      of the left lobe had increased from 405 to 554 cm3 (P < 0.0001) by 2 weeks after
      PTPE. Inflammatory grade was the only independent factor predicting regenerative
      hypertrophy (regeneration ratio (%) = 80.3 - 20.1 x grade; standard correlation
      coefficient = -0.566; P = 0.0014). Histological inflammatory activity was the
      essential factor regulating liver regeneration after PTPE in patients with
      chronic hepatitis.

PMID- 10204617
TI  - Predictive value of different hepatitis C serological assays in the treatment of
      chronic hepatitis C with interferon alpha.
AB  - In order to predict the complete response rate of natural interferon-alpha (nIFN
      alpha) treatment in patients with chronic active hepatitis C, we examined the
      predictive value (PV) of different hepatitis C serological assays. We performed
      first generation (ver.1) and second generation (ver.2) hepatitis C virus (HCV)
      branched DNA-probe assays (bDNA-probe), HCV core protein assay (core protein),
      HCV Amplicor Monitor assay (amplicor monitor), and HCV competitive polymerase
      chain reaction (competitive PCR) assay, using serum samples collected immediately
      before initiation of treatment. For each marker, we studied, in patients
      stratified by serological group (Gr), which predictive value (PV) of the HCV
      titers showed association with the therapeutic effect. In 59 Gr 1 patients,
      complete response to nIFN-alpha treatment was predicted from the following PVs
      for each marker: 0.5 Meq/ml or less (odds ratio 11.7: P = 0.0010) with ver.1, 1.0
      Meq/ml or less (odds ratio 5.3; P = 0.0119) with ver.2 of the bDNA-probe, 50
      pg/ml or less (odds ratio 10.3; P = 0.0062) with core protein, 200 x 10(3)
      copy/ml or less (odds ratio 7.8; P = 0.0031) with amplicor monitor, and 10(4)
      copy/ml or less (odds ratio 6.2; p = 0.8395) with competitive PCR. In 27 Gr 2
      patients, the PV for each marker indicating complete response was as follows:
      There was no relationship between PV and therapeutic effect with ver.1 of the
      bDNA-probe, while the PVs for the other markers were 0.2 Meq/ml or less (odds
      ratio 2.2; P = 0.3788) with ver.2, 20 pg/ml or less (odds ratio 5.6; P = 0.0597)
      with core protein, 400 x 10(3) copy/ml or less (odds ratio 4.0; P = 0.2965) with
      amplicor monitor, and 10(5.5) copy/ml or less (odds ratio 29.2; P = 0.0096) with
      competitive PCR. Our findings showed that complete response to the treatment may
      be predicted using the appropriate PV for each marker.

PMID- 10204619
TI  - Intraductal ultrasonography in six patients with endoscopic biliary stenting.
AB  - The development of endoscopic biliary stenting (EBS), using the Wallstent, to
      treat patients with obstructive jaundice secondary to unresectable tumors of the
      pancreas or biliary ducts has led to improved quality of life in these patients.
      We followed six patients with intraductal ultrasonography (IDUS) after insertion
      of a Wallstent. In two patients, endoscopic ultrasonography (EUS) was also
      performed, and in three patients IDUS was repeated every few months. IDUS allowed
      ingrowth of the tumor or formation of debris in the stent to be observed clearly
      and easily. Therefore IDUS was considered to be a powerful tool to follow
      patients after stenting and to decide on the next treatment when reobstruction
      occurred.

PMID- 10204620
TI  - Clinical evaluation of 3D-CT cholangiography for preoperative examination in
      laparoscopic cholecystectomy.
AB  - Three-dimensional-computed tomography (3D-CT) cholangiography is a 3D shaded
      surface display image of the biliary tract obtained by using helical CT after
      intravenous cholangiography or cholangiography per percutaneous transhepatic
      cholangio-drainage tube. We investigated whether 3D-CT cholangiography could
      provide a useful image, for preoperative examination in laparoscopic
      cholecystectomy. Sixty-five patients with biliary diseases were examined by 3D-CT
      cholangiography. Helical scanning was performed on a Proceed Accell (GE Medical
      Systems, Waukesha, WI, USA). Three-dimensional images were created using an
      independent workstation. A clear image of the common bile duct was obtained for
      all patients (100%) by 3D-CT cholangiography. The gallbladder was well visualized
      in 54 (93%) and the cystic duct was shown to be opacified in 55 (95%) of the 58
      patients with a gallbladder. Thirty-one patients were diagnosed as having
      gallstones by 3D-CT cholangiography (sensitivity. 72.1%; specificity, 100%;
      accuracy, 79.3%), while 43 were diagnosed as having cholecystolithiasis by
      ultrasonography. The advantages of 3D-CT cholangiography were a low level of
      invasiveness, easily obtained images compared to those obtained with endoscopic
      retrograde cholangiography (ERC), good opacification, and provision of a three
      dimensional understanding of the biliary system, especially of the cystic duct.
      When combined with ultrasonography and routine liver function tests, 3D-CT
      cholangiography was considered very useful for obtaining information before
      laparoscopic cholecystectomy. It allowed the omission of ERC in many patients who
      were considered to have no common bile duct stone, by employment of 3D-CT
      cholangiography.

PMID- 10204621
TI  - Laparoscopic drainage of an intramural duodenal hematoma.
AB  - A 21-year-old man was admitted with vomiting and abdominal pain 3 days after
      sustaining blunt abdominal trauma by being tackled in a game of American
      football. A diagnosis of intramural hematoma of the duodenum was made using
      computed tomography and upper gastrointestinal tract contrast radiography. The
      hematoma caused obstructive jaundice by compressing the common bile duct. The
      contents of the hematoma were laparoscopically drained. A small perforation was
      then found in the duodenal wall. The patient underwent laparotomy and repair of
      the injury. Laparoscopic surgery can be used as definitive therapy in this type
      of abdominal trauma.

PMID- 10204622
TI  - Primary hepatic carcinoid tumor.
AB  - A primary hepatic carcinoid tumor arising in a 49-year-old woman is reported. The
      patient was admitted with multiple hepatic tumors and treated by a left lobectomy
      and cholecystectomy. Cut sections of the specimen revealed a solid and necrotic
      mass, measuring 10 x 12 x 13 cm, with multiple small satellite nodules.
      Histologically, the tumor cells had small oval-shaped nuclei and presented with a
      trabecular arrangement and rosette-like formation. Both Grimelius and Fontana
      Mason stainings were positive. The tumor cells were positive for chromogranin A
      and negative for other antigens. Ultrastructural studies of the tumor cells
      revealed duct-like formation with microvilli and a cluster of dense small
      immature neurosecretory granules in the cytoplasm. These findings were consistent
      with those of carcinoid tumors. Postoperatively, the patient was treated with
      repeated transcatheter arterial chemoembolization for any remnant tumors.
      However, she died of the disease 5 years after the initial surgery. The autopsy
      findings suggested the primary site to be the liver.

PMID- 10204623
TI  - Refractory hepatic hydrothorax treated with transjugular intrahepatic
      portosystemic shunt.
AB  - A 66-year-old cirrhotic woman was referred to our hospital for evaluation of
      refractory pleural effusion and dyspnea. Massive right sided-pleural effusion but
      no ascites was detected. She had been treated with diuretics and albumin,
      repeated thoracenteses, and pleural drainage with an intercostal catheter, all of
      which had failed to relieve her symptoms. The diagnosis of hepatic hydrothorax
      without ascites was made by injection of technetium-99m-sulfur colloid into the
      peritoneal cavity. A transjugular intrahepatic portosystemic shunt was placed and
      successfully reduced the pleural effusion, resulting in complete relief of her
      symptoms. The patient has been free of symptoms for 18 months after the
      procedure.

PMID- 10204625
TI  - Ventral pancreatitis defined on MRI.
AB  - Ventral pancreatitis, pancreatitis localized in the embryologic ventral pancreas,
      is rare. To date, only three well documented reports of ventral pancreatitis have
      been reported in the English-language literature. All three were associated with
      pancreas divisum. This report presents a patient suspected to have ventral
      pancreatitis on endoscopic retrograde cholangiopancreatography, confirmed by
      magnetic resonance imaging.

PMID- 10204624
TI  - Management of adrenal metastasis of hepatocellular carcinoma by asynchronous
      resection of bilateral adrenal glands.
AB  - We report on a 65-year-old man who received asynchronous bilateral adrenalectomy
      for adrenal metastasis of hepatocellular carcinoma. Fifteen months after curative
      resection of right hepatic lobe for hepatocellular carcinoma, a metastatic lesion
      of the left adrenal gland was detected and left adrenalectomy was performed. Ten
      months after the second operation, a metastatic lesion in the right adrenal
      gland, associated with tumor thrombus in the inferior vena cava, was revealed.
      Transcatheter arterial embolization of the arteries feeding the metastatic tumor
      was performed, but its effects were incomplete. As there was the tumor thrombus
      in the inferior vena cava and no other intrahepatic recurrence or extrahepatic
      metastasis was found, resection of the right adrenal gland with tumor thrombus,
      without the employment of veno-venous bypass, was performed, followed by
      postoperative hormonal supplementation. Changes in the patient's alpha
      fetoprotein level were clinically useful for the detection of the metastatic
      lesions and the evaluation of therapeutic effects. Metastasis to adrenal gland
      from hepatocellular carcinoma should be actively managed, and the appropriate
      surgical treatment selected, if intrahepatic recurrence and/or other extrahepatic
      metastasis are controlled. To achieve higher curability and better outcome in
      patients with bilateral adrenal metastasis of hepatocellular carcinoma, bilateral
      total adrenalectomy is indicated, accompanied by effective postoperative hormonal
      supplementation.

PMID- 10204627
TI  - Pitfalls in serological testing for Helicobacter pylori infection in the elderly.

PMID- 10204626
TI  - Mucin-producing biliary papillomatosis associated with gastrobiliary fistula.
AB  - We report a case of mucin-producing biliary papillomatosis in a 78-year-old
      woman. Abdominal ultrasound (US) and computed tomography (CT) showed wall
      thickening and dilatation of the intrahepatic bile duct (IHBD), as well as a
      nodular lesion, 1.2 cm in diameter, in the left branch of the IHBD. Gastric
      endoscopy revealed excretion of bile-containing mucin on the anterior wall of the
      body of the stomach. Endoscopic ultrasonography (EUS) showed gastrobiliary
      fistula and discharge of mucin into the stomach. Needle biopsy of the biliary
      tumor revealed papillary proliferation, but no malignant cells were recognized
      histologically. Therefore this patient was diagnosed as having mucin-producing
      biliary papillomatosis forming gastrobiliary fistula. She did not present with
      obstructive jaundice, probably because of the fistula. She is alive, without
      obstructive jaundice, 16 months after the diagnosis without having had surgery.
      This is, to our knowledge, the first reported case of biliary papillomatosis
      forming gastrobiliary fistula and with the patient free of obstructive jaundice.

PMID- 10204628
TI  - Gene or genome? The meaning of gains/losses of chromosome.

PMID- 10204629
TI  - Proinflammatory cytokines in IBD.

PMID- 10204630
TI  - Liver regeneration after portal vein embolization.

PMID- 10204631
TI  - Further experiments are necessary to determine whether transjugular intrahepatic
      portosystemic shunt is the definitive treatment for refractory hepatic
      hydrothorax.

PMID- 10204632
TI  - A scientific perspective on macrolide susceptibility. Introduction.

PMID- 10204633
TI  - Antibiotic resistance and therapeutic options in lower respiratory tract
      infections.
AB  - The emergence of some strains of common pathogens of community acquired pneumonia
      resistant to one or more of the frequently used antimicrobials is becoming
      widespread. The clinical significance and implications of these resistance
      patterns are, however, unclear. Studies of the clinical progress of patients with
      pneumonia or bacteraemia infected with penicillin-resistant organisms show that
      patients frequently recover when treated with penicillins or cephalosporins. Beta
      Lactam drugs and macrolides are still associated with clinical success in lower
      respiratory tract infections despite increasing resistance to these agents in
      vitro. Therefore, when making therapeutic choices, in vitro resistance data
      cannot always be used to predict clinical outcome. Infections caused by resistant
      organisms can usually be successfully treated using traditional therapeutic
      approaches.

PMID- 10204634
TI  - Pharmacological considerations in the emergence of resistance.
AB  - Resistance to macrolides in vitro is increasingly being reported. However, there
      has been no corresponding increase in clinical failures noted. Lack of clinical
      failures due to resistance is most likely the result of the high intracellular
      concentrations that these drugs achieve in phagocytes. In the case of
      clarithromycin, concentrations in both monocytes and granulocytes fluctuate
      between peaks of approximately 22-25 mg/l and troughs of approximately 5 mg/l
      during a standard dosing interval. In contrast, azithromycin attains
      concentrations of over 60 mg/l in granulocytes and at least 100 mg/l in
      monocytes. After 7 days, azithromycin concentrations of >32 mg/l are still
      observed. These data also imply that against pathogens with increasing minimum
      inhibitory concentrations (MICs), macrolides with relatively lower or less
      sustained intracellular concentrations will become ineffective clinically much
      sooner than compounds, such as azithromycin, that concentrate to a high degree
      and are retained in white blood cells for prolonged periods.

PMID- 10204635
TI  - Susceptibility and resistance emergence studies with macrolides.
AB  - An extended elimination half-life and good tissue penetration enable oral
      azithromycin to attain high and prolonged concentrations in infected tissues,
      yielding high antibacterial activity in vivo. It has been suggested, however,
      that prolonged subinhibitory concentrations of azithromycin from 2 to 4 weeks
      after therapy may lead to the emergence of azithromycin resistance in vivo,
      compared with other macrolide antibiotics. Data from two types of in vitro
      susceptibility studies, an animal tissue infection model, and a clinical
      pediatric study demonstrate that prolonged tissue concentrations of azithromycin
      are unlikely to lead to the emergence of resistance in the clinical setting.
      Further, data from in vitro susceptibility studies indicate that resistance to
      macrolides, and azithromycin in particular, is significantly over-estimated for
      bacterial strains incubated in the presence of CO2.

PMID- 10204636
TI  - Macrolides and changes in the oral flora.
AB  - Macrolides have been used in dental practice for many years, and may have a role
      in treating periodontal disease. Increased numbers of antibiotic-resistant oral
      streptococci have been reported after administration of both penicillins and
      macrolides. We confirm these findings for erythromycin, josamycin and
      azithromycin, and show that small numbers of macrolide-resistant streptococci are
      part of the normal oral flora at baseline. Resistant organisms fill the vacuum
      created by the removal of sensitive strains by antibiotic treatment. Following
      treatment with azithromycin, periodontal bacterial pathogens such as black
      pigmented anaerobes and spirochaetes decrease, whereas numbers of oral
      streptococci increase. These changes in the oral flora indicate a return to a
      healthier oral environment. In our studies, no clinical problems resulted from
      the transient increase in macrolide-resistant streptococci.

PMID- 10204637
TI  - A scientific perspective on macrolide susceptibility. Conclusion.

PMID- 10204639
TI  - The balance of positive and negative effects of specific messages in the
      evaluation of interventions for preventing HIV infection.
AB  - The study objectives were to determine the effects of a large-scale school-based
      HIV prevention campaign, in terms of both positive and negative effects of each
      single message, and to identify sub-populations more at risk. Forty-six schools,
      randomly sampled from all schools in the Lazio region, were randomized to either
      an intervention or a control group. The study population consisted of 3866
      students. Questionnaires on AIDS-related knowledge and risk perceptions were
      administered to students before and after the intervention. Odds ratios were
      calculated to represent the extent to which the intervention was associated with
      an improvement (OR+), and the extent to which it prevented a worsening (OR-).
      Overall, the intervention was successful in communicating important messages,
      such as the impossibility of transmitting HIV through social contacts (OR+ all
      significantly > 1 and OR- always< 1), the meaning of 'seropositivity' (OR+: 1.28,
      95% CI: 0.99-1.64; OR-: 0.73, 95% CI: 0.58 0.91), and the lack of a resolutive
      cure for AIDS (OR+: 1.61, 95% CI: 1.10-2.36; OR-: 0.76, 95% CI: 0.57-1.02). The
      worst results were observed in vocational and art schools, where OR + > 1 were
      observed for only three questions and OR- values usually exceeded 1. This study
      highlights the necessity of remodelling the intervention, indicating which
      messages need to be modified. The low impact of educational programmes among
      students of vocational and art schools makes them a population more at risk, that
      should be considered as a priority target population for interventions.

PMID- 10204638
TI  - Cell-associated infectious HIV-1 viral load as a predictor of clinical
      progression and survival among HIV-1 infected injection drug users and homosexual
      men.
AB  - Cell-associated infectious HIV-1 viral load was measured using semi-quantitative
      microculture techniques to determine its predictive capability for progression to
      AIDS or survival among HIV-1 infected injecting drug users (IDU) and homosexual
      men (HM). The authors followed 296 IDU and 240 HM from February 1992 through
      September 1995 for: (i) death, (ii) AIDS, and (iii) AIDS or bacterial infection.
      At baseline, viral load was quantified using microculture techniques to determine
      infectious units per million peripheral blood mononuclear cells (IUPM). Data were
      analyzed using standard statistical methods for survival analysis. Of the 536
      total participants, 106 died (20%), and 98 of the 481 AIDS-free participants
      developed AIDS (20%). The relative hazard of AIDS for a viral load of > or = 100
      IUPM, relative to a negative culture (0 IUPM), was 6.73 (95% CI: 2.23-20.3) after
      adjusting for risk group, initial CD4+ count, and other covariates. The adjusted
      relative hazard of death for a viral load of > or = 100 IUPM vs. 0 IUPM was 2.57
      (95% CI: 0.97 6.80). Viral load predicted time to death within the < 200 cells/ul
      CD4+ stratum. The predictive value of viral load on HIV-1 progression did not
      vary by risk group. These data show that cell associated infectious HIV-1 viral
      load was significantly predictive of progression across risk groups for AIDS and
      death among those severely immune compromised.

PMID- 10204640
TI  - How do general practitioners approach hepatitis C virus screening in France?
AB  - To estimate the prevalence of infection by hepatitis C virus (HCV) in general
      practice, and to investigate attitudes to screening for HCV, a specific
      questionnaire was sent to the sentinel general practitioners (SGPs) of the French
      Sentinel Network. From the figures reported by SGPs, the number of anti-HCV tests
      performed in general practice during the six months before the survey (July
      December 1994) was extrapolated to about 350,000 tests for the whole of France
      during all of 1994 (95% CI: 314,000 382.000). Of the 312 participating SGPs, 224
      (72%) had prescribed at least one anti-HCV test during these six months. and 217
      (70%) knew of at least one anti-HCV-positive patient in their practice. With
      regard to their screening attitudes. 244 SGPs (78%) said they had prescribed anti
      HCV tests for patients with no signs of previous or recent hepatitis infection;
      SGPs who had at least two HCV-positive patients in their practice were more
      likely to screen for anti-HCV than SGPs who did not (94% vs. 72%, p < 0.001). The
      main reason for prescription were that patients had an anti-HIV-positive status,
      were intravenous drug users and/or were blood transfusion recipients. For the 88
      SGPs who had not prescribed any anti-HCV test during the six months before the
      study, the main reasons given were that few patients were at risk in their
      practice (81 SGPs) and that the risk factors for HCV infection were not well
      known (12 SGPs). Only 6 SGPs gave the absence of effective treatment as a reason
      for non-prescription. From the figures reported by SGPs, we extrapolated to
      100,000 (95% CI: 90,000-110.000) the number of anti-HCV-positive patients known
      by the 52,000 French general practitioners in 1994. These results indicate that
      the Sentinel network may be a useful tool for assessing the evolution of
      attitudes to HCV screening in general practice.

PMID- 10204641
TI  - A study on the role of the family and other risk factors in HCV transmission.
AB  - BACKGROUND/AIMS: To understand the intrafamilial transmission and the existing
      risk factors related to HCV infection in subjects confirmed anti-HCV positive,
      their sexual partners and household contacts in Friuli, North-East Italy.
      METHODS: We enrolled all the subjects that were consecutively identified as HCV
      positive during routine laboratory testing in six health districts and their
      household contacts. From each subject we obtained a blood sample, demographic
      data and a medical history including the existence of risk factors for HCV.
      Antibodies to HCV were detected employing a commercially available second
      generation enzyme immunoassay (EIA); positive serum specimens were retested using
      a second-generation recombinant immunoblot assay (RIBA-2). RESULTS: We recruited
      743 subjects, 229 first subjects identified as HCV positive and 514 household
      contacts. There were no statistically significant differences in positivity among
      household contacts. Analysing intracouple transmission we found no significant
      differences by gender in couples both with and without parenteral risk factors.
      We found, both with univariate and multivariate analysis, as statistically
      significant risk factors in all the subjects: age older than 60, blood
      transfusions (particularly those performed before 1984), surgical procedures such
      as abortion and/or uterine curettage, history of HBV infection, intravenous drug
      use, and tattooing. CONCLUSIONS: Our results stress the low relevance of sexual
      transmission in the intrafamilial context, the importance of abortion and/or
      uterine curettage, the important role of blood transfusions in the past, a higher
      prevalence of HCV infection within a household of a HCV positive member compared
      to all other existing data in the area.

PMID- 10204643
TI  - Ill-defined and multiple causes on death certificates--a study of
      misclassification in mortality statistics.
AB  - Biases can distort, limit or inhibit the value of mortality data as an
      epidemiological re source. From 9500 deaths occurring in Naples (Italy during
      1994, a random sample of 372 death certificates reporting ill-defined causes and
      multiple causes of death was extracted. The code for the underlying cause on the
      death certificate (assigned code) was compared with the cause reattributed with
      the aid of interview of the certifying physician or clinical records (modified
      code). The aim was to investigate the extent of misclassification of 'underlying
      cause' in deaths attributed to ill-defined and/or multiple causes and the
      shortcomings in the ICD-IX. Ill-defined underlying causes of death (7.0% of death
      certificates) were cardiovascular diseases, tumours with no specified site or
      nature, symptoms, signs, ill-defined conditions and senility. There was
      disagreement between the initially assigned code and the modified code in 53.8%
      of ill-defined underlying causes; discordance was high for the certificates
      filled in by the family physician. Multiple causes of death were observed in
      23.6% of certificates; of these 59.2% concerned subjects aged 75 years and over
      at death. Diabetes was always listed in association with other pathologies but
      neoplasms and traumas were generally listed alone. Disagreement between codes
      occurred in 48 (54.5%) certificates indicating multiple causes. In 10 of them,
      death was established as due to a concurrence of causes. As regards ill-defined
      causes of death, the authors concluded that specific training on certifying
      procedures would be insufficient on their own; the physician should be made aware
      that certification is a fundamental requirement for building up epidemiological
      data. Evidence-based educational interventions are needed. As regards multiple
      causes of death, multicausal analysis may be indicated for deaths due to a
      concurrence of causes.

PMID- 10204642
TI  - The effect of user charges and socio-demographic environment on paediatric trauma
      hospitalisation in Helsinki in 1989-1994.
AB  - Although many studies have shown an association between socio-economic
      environment and childhood injury mortality rates, little research has focused on
      the association between injuries which require hospitalisation and the child's
      socio-economic environment. All municipal emergency care was free of charge
      before the beginning of 1991, from then on a moderate patient charge was
      introduced by the City of Helsinki. An earlier report from a completely different
      social environment suggest that even a moderate user charge might create
      systematic discrimination against indigent families. We studied the childhood
      injury hospitalisation rates during 1989-1994 in Helsinki and analysed the
      association between rates of hospitalisation and local socio-economic and
      demographic factors. We also examined the effect of introduction of emergency
      room user charges on the rate of hospitalisation. Data from 1607 injuries from
      Helsinki City Hospital and 769 injuries from Helsinki University Central Hospital
      from years 1989 through 1994 were used. Annual rates of child hospitalisation
      were calculated at city level. Local socio-economic and demographic variables
      were derived from the Helsinki Bureau of Statistics. The possible association
      between the explanatory variables and hospitalisation rates at Helsinki City
      Hospital was calculated using annual data from the 33 health districts in
      Helsinki. The overall rate of hospitalisation for injuries declined but not
      statistically significantly. No association between socio-economic and
      demographic variables and hospitalisation rates was found. The moderate user
      charge had no effect on hospitalisation rates, proving that, in this setting, the
      demand for care was rather inelastic in paediatric injuries severe enough to
      require hospitalisation.

PMID- 10204644
TI  - Surveillance of hospital acquired infections: presentation of a computerised
      system.
AB  - Day by day surveillance of hospital acquired infections is a time-consuming
      activity. Healthcare professionals need powerful computer tools to manage and
      analyse these data. Such a program must include all the functions needed to
      manage communication with other programs in order to minimise data entry.
      Coherence checks are then used to validate data. Automatic production of reports,
      graphics or tables enables users to quickly obtain timely and representative
      documents regarding the evolution of specific indicators. The local person in
      charge for the system must be able to easily modify many parts of the program
      (data entry screens, calculations, checks, etc.) without any direct intervention
      from a computer specialist. Using this description, we have created a specific
      software for the management of this information named NosoCom. The program has
      been used for four years in France and Belgium. An English release is now
      available.

PMID- 10204645
TI  - Validation of stroke diagnosis in the National Hospital Discharge Register and
      the Register of Causes of Death in Finland.
AB  - The validity of stroke diagnosis in the National Hospital Discharge Register and
      the Register of Causes of Death was examined among 546 middle-aged men in
      Finland. The subjects were cases of cerebrovascular diseases of the Alpha
      Tocopherol, Beta-Carotene Cancer Prevention Study and identified by record
      linkage to the registers. In all, 375 events with cerebrovascular disease as
      hospital discharge diagnosis and 218 events with cerebrovascular disease as the
      underlying cause of death were reviewed using specific criteria modified from the
      classifications of the National Survey of Stroke and the WHO MONICA Study. For
      hospital stroke diagnoses, there was agreement on diagnosis for all strokes in
      90%, for subarachnoid hemorrhage in 79%, intracerebral hemorrhage in 82%, and
      cerebral infarction in 90%. The respective agreement rates for stroke as the
      underlying cause of death were 97%, 95%, 91%, and 92%. The data were insufficient
      for review in 1% and 3% of the stroke events, respectively. Age, observation year
      and trial supplementation with alphatocopherol or beta-carotene had no effect on
      validity. In conclusion, the validity of stroke diagnosis was good in registers
      of hospital diagnoses and causes of death justifying their use for endpoint
      assessment in epidemiological studies.

PMID- 10204646
TI  - Cognitive function in the Caerphilly study: associations with age social class,
      education and mood.
AB  - Baseline cognitive function was established for a study of pre-symptomatic
      cognitive decline in 1870 men from the general population aged 55-69 years as
      part of the third examination of the Caerphilly Study. Cognitive assessment
      included the AH4, a four choice serial reaction time task, a modified CAMCOG,
      MMSE, NART and various memory tests. Distributions and relationships with age,
      social class, education and mood at time of testing are presented for a younger
      population than has previously been available. Multiple linear regression showed
      cognitive function to be independently associated with all four factors. The age
      effect was equivalent to one half of a standard deviation (SD) in CRT and AH4
      scores. Only the NART score was not associated with age, supporting the use of
      NART score as an estimate of pre-morbid IQ. The largest age adjusted differences
      between men with low and normal mood were for the AH4 (3 points, t = 5.6, p <
      0.0001) and the CAMCOG (2 points, t = 5.8, p < 0.0001). The smallest age adjusted
      effect of mood was for the CRT (33 ms, t = 2.14, p = 0.32) and the MMSE (0.4
      points, t = 2.97, p = 0.003). Age, mood and education adjusted social class
      effects were very large ranging between around 0.5 SD for the CRT, and 1.0 SD for
      the AH4 and NART, respectively. For educational status age, mood and social class
      adjusted differences were also substantial with tests for trend showing the
      largest differences for the NART (t = 12, p < 0.0001) and modified CAMCOG (t =
      10.6, p < 0.0001) with the smallest differences for the CRT (t = 2.73, p =
      0.006).

PMID- 10204647
TI  - Neonatal tetanus: a continuing challenge in the southeast of Turkey: risk
      factors, clinical features and prognostic factors.
AB  - Neonatal tetanus (NT) still causes significant mortality in developing countries,
      although in 1989 WHO adopted the goal of eliminating the disease by 1995-2000. To
      characterize the regional characteristics, clinical charts of 55 neonates (42
      males and 13 females) admitted to the Pediatric Infectious Diseases Ward of Dicle
      University Hospital, Diyarbakir, Turkey with the diagnosis of NT from 1991 to
      1997 were reviewed. Mean age at admittance was 8.9+/-4.3 days with a range of 3
      25 days. Mean period for the appearance of first symptoms was 5.8 days ranging
      between 1 and 21 days. Mean birth weight of the patients was 3369+/-560g. All
      patients were from rural areas and were delivered at home by untrained
      traditional birth attendants with no prior antenatal healthcare services. Razor
      blade (55%), scissors (27%), and knife (18%) were the instruments used to cut the
      cord in non-hygienic conditions. No mothers had prior vaccination with tetanus
      toxoid during their pregnancy. Spasticity (76%), lack of sucking (71%), trismus
      (60%), fever (49%), omphalitis (44%), irritability (24%), risus sardonicus (22%),
      and opithotonus (15%) were the most common presenting signs and symptoms. Age at
      admission < 7.5 days and symptoms of onset <4.9 days, risus sardonicus and
      opisthotonus were associated with fatal outcome. All patients were treated with
      human tetanus immunglobulin or equine tetanus antitoxin where available,
      antibiotic therapy by penicillin G (100.000 U/kg/day) and intravenous high dose
      diazepam (40 mg/kg/day). Overall mortality rate was 40% (22 cases), without any
      equipment for mechanical ventilation. Health education of mothers and birth
      attendants, promotion of hospital delivery and prenatal tetanus immunization of
      all pregnant women particularly in rural areas are recommended, if NT is to be
      prevented.

PMID- 10204649
TI  - The diuretic effects of alcohol and caffeine and total water intake
      misclassification.
AB  - Data from the 1994 USDA nationwide survey (CSFII) on 190 non-smoking males (aged
      20-29) were used to propose a method for adjusting total water intake for the
      diuretic effects of caffeine and alcohol, and evaluate the potential for related
      misclassification bias. The data were processed on a per meal basis. Under the
      assumption that subjects were in water balance at the start of the survey day,
      water losses due to caffeine (1.17 ml/mg caffeine) and alcohol (10 ml/g alcohol)
      were subtracted from crude intake estimates. If water intake for one meal was
      inadequate for excretion of the associated osmotic load at 750 mosmol/l, water
      losses for the subsequent meal were reduced by 32%. Unadjusted and adjusted mean
      total water intakes differed by 321.5 g. Misclassification appeared worst at
      higher water intakes. Linear regression models, each with a water intake variable
      as an independent variable and body mass index as the outcome, were fit to
      evaluate the potential for alcohol- and caffeine-related misclassification bias.
      Misclassification resulted in large changes (all >10%) in linear regression
      estimates of effect. Future studies of water-disease relationships, especially
      those intending to compare extremes of total water intake, should consider
      caffeine- and alcohol-related misclassification bias.

PMID- 10204651
TI  - Inadequate risk factor analysis for knee arthrosis.

PMID- 10204648
TI  - Outbreaks of gastroenteritis caused by SRSVs from 1987 to 1992 in Kyushu, Japan:
      four outbreaks associated with oyster consumption.
AB  - From 1987 to 1992, 18 outbreaks of acute non-bacterial gastroenteritis occurred
      in Kyushu district. The most common symptoms were diarrhea, vomiting, nausea and
      abdominal cramp. Small round structured viruses (SRSVs) were detected in 52
      (44.8%) of 116 stool samples from 17 outbreaks by the electron microscopy (EM)
      method, and a significant increase in the antibody level was noted in 42 (80.7%)
      of 52 paired serum samples from 12 outbreaks by the immune electron microscopy
      (IEM) method and in 18 (51.4%) of 35 samples from 8 outbreaks by the western blot
      (WB) method. However, according to the WB method, antigen-antibody reaction was
      not observed to reference antigen strips (SRSV-9/Tokyo 86-510, 63 kDa) in three
      of the 8 outbreaks. The detected virus was regarded as an etiologic agent for
      these outbreaks. In four of 5 outbreaks which appeared associated with eating raw
      oysters, there was a close relation between SRSV infection and consumption of raw
      oysters.

PMID- 10204650
TI  - Pigmentary traits, nevi and skin phototypes in a youth population of Central
      Italy.
AB  - Five thousand eight hundred and thirty-seven healthy young men, aged 18-19, from
      two distinct regions of Central Italy, Abruzzo and Marche, have been investigated
      during the military medical examination to evaluate pigmentary traits and skin
      phototypes. They were examined over the entire body except the scalp and ano
      genital area for pigmented lesions, which included common acquired melanocytic
      nevi (MN), clinically atypical nevi and solar lentigines. Eye and hair color were
      also recorded. Information was gathered by self-questionnaire, personal interview
      and clinical skin examination performed by two independent dermatologists. For
      sunlight susceptibility and sun exposure, each subject was classified from I to
      IV skin phototype according to the classification of sun-reactive skin types as
      proposed by Fitzpatrick. Almost half of the entire population (44.5%) had
      affirmed that they tanned easily and rarely burned (phototype IV), 10.3% had skin
      phototype I or II, 11.2% had more than 40 common MN, and 37.2% had atypical nevi
      with a diameter > or = 5 mm. The common MN and atypical nevi count had a
      significant association with skin phototype. Subjects with phototype I or II, and
      solar lentigo had significantly higher nevus counts than individuals without
      these characteristics.

PMID- 10204652
TI  - Heparin and low-molecular-weight heparin therapy for venous thromboembolism. The
      twilight of anticoagulant monitoring.
AB  - Recent improvements in the methods of clinical trials and the use of accurate
      objective tests to detect venous thromboembolism have made possible a series of
      randomized trials to evaluate various treatments for venous thromboembolism. The
      results of these trials have resolved many of the uncertainties a clinician
      confronts in selecting an appropriate course of anticoagulant therapy. These
      trials have shown that the intensity of both initial heparin treatment and long
      term anticoagulant therapy must be sufficient to prevent unacceptable rates of
      recurrence of venous thromboembolism. Patients with proximal deep vein thrombosis
      who receive inadequate anticoagulant therapy have a risk of clinically evident,
      objectively documented recurrent venous thromboembolism that approaches 20% to
      25%. The need for therapy with heparin and the importance of monitoring blood
      levels of the effect of heparin have been established. The importance of
      achieving adequate heparinization was suggested by a nonrandomized trial in 1972
      and randomized trials in the 1980s have confirmed this finding. Furthermore,
      randomized trials have demonstrated the importance of achieving adequate
      heparinization early in the course of therapy. Unfractionated intravenous heparin
      has provided an effective therapy for more than half a century, but the need to
      monitor therapy and establish therapeutic levels is a fundamental problem. It is
      evident that validated heparin protocols are more successful in establishing
      adequate heparinization than intuitive ordering by the clinician. However, even
      with the best of care using a heparin protocol, some patients treated with
      intravenous heparin will receive subtherapy. In this context, subtherapy reflects
      a practical limitation of the use of unfractionated heparin, rather than a poor
      standard of care. Furthermore, it is recognized that the practical difficulties
      associated with heparin administration are compounded by the substantive
      practical difficulties of standardizing APTT testing and the therapeutic range.
      Our findings emphasize the confounding effect that initial heparin treatment has
      on long-term outcome. In future trials of longterm therapy, it is imperative that
      the initial therapy is of adequate intensity and duration; failure to administer
      adequate initial treatment may lead to a poor outcome that is falsely attributed
      to the long-term therapy under evaluation. Therapy with low-molecular-weight
      heparin, which does not require monitoring and dose finding, is the likely
      practical solution to these dilemmas. Based on the experience of difficulties
      achieving adequate therapy with subcutaneous unfractionated heparin dosing, we
      administered a low-molecular-weight heparin formulation in a single daily dose,
      rather than splitting the treatment into 2 equal doses. The initial intensity of
      therapy was thereby maximized. Therapy with low-molecular-weight heparin proved
      to be better than therapy with unfractionated heparin.

PMID- 10204653
TI  - Prothrombotic and lipoprotein variables in patients attending a cardiovascular
      risk management clinic: response to ciprofibrate or lifestyle advice.
AB  - BACKGROUND: Lipid lowering drugs improve survival. However, intervention studies
      have focused on reducing serum total cholesterol and low density lipoprotein
      (LDL) concentrations and have not considered that levels of high density
      lipoprotein (HDL), triglycerides (TG), lipoprotein (a) and fibrinogen also
      predict risk and outcome. METHODS: A retrospective survey of patients with
      primary dyslipidaemia attending a cardiovascular risk management clinic (set in a
      university hospital) was initiated to assess the effect of ciprofibrate, a drug
      with the potential to modify all these variables. Patients who received
      ciprofibrate (n = 72) were compared with 64 patients who only received lifestyle
      advice. Both groups had a similar age and gender distribution. The ciprofibrate
      group had a higher cardiovascular risk load but both groups shared several other
      characteristics. Fasting serum total cholesterol, LDL, HDL, TG, lipoprotein (a),
      glucose and plasma fibrinogen concentrations were measured at baseline and after
      2-4 months. RESULTS: Ciprofibrate significantly improved total cholesterol, LDL,
      HDL, TG, lipoprotein (a) and fibrinogen. In contrast, lifestyle advice only
      significantly (but less markedly) reduced serum total cholesterol and TG
      concentrations. CONCLUSIONS: In a clinical setting, ciprofibrate has a broad
      spectrum of action on several predictors of vascular events. Although our study
      is not of a double blind randomized design it reflects the conditions in clinical
      practice. Nevertheless, this type of survey has its limitations.

PMID- 10204654
TI  - Ten-year results following elective surgery for abdominal aortic aneurysm.
AB  - OBJECTIVE: 10-year results after elective operation for infrarenal aortic
      aneurysm considering the influence of risk factors. EXPERIMENTAL DESIGN:
      Retrospective study with 5-12 year postoperative follow-up. SETTING: University
      hospital (Klinikum Grosshadern, Munich). PATIENTS: The long-term follow-up was
      based on 521 (95.6%) out of 545 consecutive patients operated upon electively for
      abdominal aortic aneurysm between 1978 and 1987. INTERVENTIONS: The infrarenal
      aneurysms were excluded by aortic tube grafts (314 patients, 59%) or bifurcation
      grafts (231 patients, 41%). MEASURES: The birthday, operation day and eventually
      the day of death in the hospital were documented in the charts. The patient's
      state or cause of death were elicited on the phone 5 to 12 years after the
      operation. Kaplan-Meier survival curves were calculated based on these data and
      compared to age-matched normal male populations. RESULTS: Hospital mortality was
      6.4%. The cumulative rate of survival following elective surgery was 65% at 5
      years and 41% at 10 years, the mean survival time being 95.1 months. Age,
      coronary artery disease and hypertension had a significant influence on the
      cumulative survival. Patients with aorto-coronary bypass had a better long-term
      outcome than those without bypass surgery. CONCLUSIONS: The excellent long-term
      results within a high-risk population support elective surgery of infrarenal
      aortic aneurysms. Results of new interventional techniques will have to be
      compared with this "golden standard" follow-up.

PMID- 10204655
TI  - Fatal late multiple emboli after endovascular treatment of abdominal aortic
      aneurysm. Case report.
AB  - BACKGROUND: The short term experience of endovascular treatment of abdominal
      aortic aneurysms (AAA) seems promising but long term randomised data are lacking.
      Consequently, cases treated by endovascular procedures need to be closely
      followed for potential risks and benefits. CASE REPORT: A 70 year-old mildly
      hypertensive male without previous or present arteriosclerotic, pulmonary, or
      urological manifestations was subjected to endovascular treatment after his mass
      screening diagnosed abdominal aortic aneurysm had expanded to above 5 cm in
      diameter, the aneurysm having been found by CT-scanning and arteriography to be
      endovascularly treatable. A Vanguard bifurcated aortic stent graft was implanted
      under epidural/spinal anaesthesia and covered by cephalosporine and heparin (8000
      IE) protection. Apart from treatment of a groin haematoma and stenosis of the
      left superficial femoral artery, the postoperative period presented no problems.
      A few days before the monthly follow-up visit, the patient developed uraemia,
      gangrene of one foot and dyspnoea. Blood glucose and LDH was elevated.
      Deterioration led to death a month and a half after stent implantation. Autopsy
      showed extraordinary large, extensive soft, brown vegetations in the lower part
      of the thoracic aorta above the properly infrarenally-placed stent. Microscopic
      examination revealed multiple microemboli in the liver, spleen, pancreas,
      intestines, testes, and especially the kidneys. DISCUSSION: Early death from
      microemboli after aortic stent implantation has been reported. However, the
      present case developed fatal multiple microemboli so late that they could not
      have originated from the excluded mural thrombus. The sudden death of an
      otherwise healthy man of extensive microemboli is difficult to explain. The stent
      application may have altered the proximal flow and wall movements disposing to
      microemboli in the case of vegetations.

PMID- 10204656
TI  - Chylous complications after abdominal aortic surgery.
AB  - Two patients developed chylous complications following abdominal aortic aneurysm
      repair. One patient had chylous ascitis and was successfully treated by a
      peritoneo-caval shunt. The other patient developed a lymph cyst, which gradually
      resorbed after puncture. Chylous complications following aortic surgery are rare.
      Patients in bad a general condition should be treated by initial paracentesis and
      total parenteral nutrition, supplemented by medium-chain triglyceride and low-fat
      diet. If no improvement is observed on this regimen, the next step should be
      implementation of a peritoneo-venous shunt, whereas direct ligation of the leak
      should be reserved for those who are not responding to this treatment.

PMID- 10204658
TI  - Measurements of calf muscle pump efficiency during simulated ambulation.
AB  - OBJECTIVE: To determine the acceptability and reproducibility of a novel method
      of measuring calf muscle pump efficiency (CMPE). If confirmed, to examine if the
      results had implications for the use of elastic compression stockings.
      EXPERIMENTAL DESIGN: A system devised to measure pressure/volume relationships in
      the calf during simulated ambulation and from which may be derived a value for
      CMPE. SETTING: A temperature/humidity controlled vascular laboratory.
      PARTICIPANTS: The study groups were normal subjects and patients with leg pain of
      more than three months duration with and without chronic venous insufficiency
      (CVI) identified using infra-red photoplethysmography. RESULTS: The system
      described is widely acceptable and reproducible (r = 0.923). Group analysis
      showed a significant reduction of CMPE in patients with CVI. However, CMPE varies
      widely in these patients. Some patients with insufficiency of the deep veins have
      a normal CMPE. CONCLUSIONS: These findings have implications for the use of
      elastic compression stockings and the degree of compression applied.

PMID- 10204657
TI  - Carotid duplex ultrasonography: importance of standardisation. Asymptomatic
      Carotid Surgery Trial Collaborators and Vascular Laboratories.
AB  - BACKGROUND: Carotid duplex ultrasonography (CDUS) is an established non-invasive
      tool for assessing patients with suspected carotid bifurcation disease. Current
      trends show an increased dependence on CDUS in recommending patients for stroke
      prevention surgery. The aim of the study was to evaluate routine practice in
      vascular laboratories across 26 countries participating in The Asymptomatic
      Carotid Surgery Trial (ACST), and to determine the areas which are in need of
      future standardisation if CDUS is to be the primary tool in recommending patients
      for CEA. METHODS: Retrospective. Information was gathered from questionnaires,
      and 22 on-site visits of vascular laboratories between August 1996 to September
      1997. SETTING: Clinical vascular laboratory practice. PARTICIPANTS: Eligible
      participants were vascular laboratories of ACST collaborators. MEASURES:
      Laboratories were compared in 7 categories: ultrasound equipment, operators,
      experience, protocols, stenosis evaluation, interpretation criteria, and
      reporting. RESULTS: Information on 117 respondents showed that (i) experience: at
      least one operator in each laboratory had more than 3 years experience; (ii)
      equipment: 88% (103/117) had colour duplex capability; (iii) operators: 54% of
      laboratories had exams performed by technologists, 33% vascular surgeons, 28%
      radiologists, and 35% other. The most significant findings were in (iv) stenosis
      evaluation: only 29% (33/117) were using a standardised Doppler angle (this
      single factor may greatly alter exam results); and (v) interpretation criteria;
      with >41 different criteria reported. These specific laboratory variations can
      affect those patients considered appropriate for CEA. CONCLUSIONS: This study
      highlights the most significant areas for future standardisation to be Doppler
      angle and interpretation criteria, if CDUS is to be a primary tool in
      recommending patients for CEA, when indicated by clinical trial results.

PMID- 10204659
TI  - Diameters of acute proximal and distal deep venous thrombosis of the lower limbs.
AB  - BACKGROUND: Duplex ultrasonography of the veins in the diagnosis of deep venous
      thrombosis (DVT) can be interpreted in a semi-quantitative mode by measuring the
      antero-posterior (AP) diameter of the thrombus. We report the values of the
      diameters of thrombi and the factors influencing these values. Therefore we
      propose a quantitative definition for DVT in duplex ultrasonography. METHODS:
      1,017 patients (3,767 thrombosed venous segments), referred to the Emergency
      Angiology Unit from January 1994 to September 1996. Characteristics: 55% F, 45%
      M; mean age 68+/-18 years; 624 proximal DVT (61%) and 393 distal DVT (39%).
      Measurement by venous echography of the antero-posterior diameters of thrombi at
      25 predetermined sites in the area of the vena cava. RESULTS: (In mm, median,
      10th and 90th percentiles after regrouping of contiguous anatomical sites not
      statistically different): thrombus in the common iliac veins and the inferior
      vena cava (12 mm, 7-17); external iliac and common femoral veins (9 mm, 5-14);
      superficial femoral, deep femoral and popliteal veins (6 mm, 4-10); calf veins (5
      mm, 4-8). The age of the patients, their sex, body mass index (BMI), whether they
      were in- or outpatients or the laterality of the thrombus never significantly
      influenced its diameter. CONCLUSIONS: It is very unusual to observe a diameter of
      under 5 mm in cases of DVT. For clinical research therefore, we propose 5 mm as
      the minimum threshold value for this diagnosis. This value could be used in the
      venous echographic definition of DVT, as a criterion for inclusion in a
      therapeutic trial, for example, or in an epidemiological study.

PMID- 10204661
TI  - Jugular venous aneurysms: when and how to operate.
AB  - BACKGROUND: Jugular venous aneurysms are rare, usually congenital, and present
      particular problems in management. Whether to perform surgery or not is
      controversial, cosmetic considerations being the primary factor in the decision.
      METHODS: Over the past nine years, 10 patients with unilateral jugular venous
      aneurysms have been closely followed up in our department. The most informative
      diagnostic procedure for the condition was considered to be ultrasonographic
      imaging after a positive Valsalva manoeuver, but in six cases phlebography was
      necessary. Various operative techniques were used--venous ligation, tangential
      venorrhaphy with or without aneurysm resection and autovenous banding, according
      to the pathological findings. RESULTS: No complications from the surgery were
      reported. Over a follow-up period ranging from six months to eight years both
      operated and non-operated patients were found to be doing equally well.
      CONCLUSIONS: Problems with the terminology of the disease, its diagnosis and the
      indications for surgery are discussed. Surgical methods are reviewed and a new
      operative technique is presented. We conclude that apart from cosmetic
      considerations, thrombosis and aneurysmal expansion are the principal indications
      for surgery.

PMID- 10204660
TI  - External banding valvuloplasty of the superficial femoral vein in the treatment
      of recurrent varicose veins.
AB  - OBJECTIVES: The aim of this study is to evaluate the efficacy of reconstructive
      surgery of primary deep venous insufficiency in preventing recurrent varicose
      veins. DESIGN: Retrospective analysis of patients affected by recurrent varicose
      veins submitted to external banding valvuloplasty of the superficial femoral
      vein. SETTING: A division of vascular surgery in a hospital/scientific institute.
      MATERIALS: Nineteen limbs (19 patients) with recurrent varicose veins, severe
      chronic venous insufficiency and 3rd or 4th grade reflux in the superficial
      femoral vein and competence of the profunda femoris vein were selected for
      surgical reconstructive treatment after a complete diagnostic study by continuous
      wave Doppler duplex scanning and descending phlebography. INTERVENTIONS: External
      banding valvuloplasty of the superficial femoral vein was performed in all cases:
      A Dacron sleeve was used in nine patients and Venocuff in 10. RESULTS: In one
      case a deep venous thrombosis of the calf occurred in the first postoperative
      period; in three cases the correction of the deep reflux was incomplete and a
      recurrence of the varices was observed. After a mean follow-up of 50 months,
      abolition of reflux and relief of symptomatology were obtained in 15 cases (78%).
      CONCLUSIONS: Primary deep venous insufficiency, unknown at the time of the
      initial operation, may be the cause of recurrent varicose veins. External banding
      valvuloplasty of the superficial femoral vein may abolish the reflux and correct
      venous hypertension, preventing recurrences.

PMID- 10204662
TI  - Decreased beta2 adrenergic mediated venodilatation in Native Americans.
AB  - BACKGROUND: A considerable body of research has been accumulated regarding the
      pathogenesis and treatment of hypertension in Whites (Caucasians) and in Blacks.
      This research has led to more effective therapies geared specifically towards
      these ethnic groups. Unfortunately, very little information is available
      regarding the pathogenesis of hypertension and the effect of antihypertensive
      treatment in Native Americans (North-American Indians). Ethnic variability in the
      response to adrenergic mediated stimulation has been previously described, and
      reduced compliance of the venous system has been suggested among the possible
      mechanisms responsible for essential hypertension. The aim of this study was to
      compare venous responsiveness between Native Americans and Whites to vasoactive
      substances. METHODS: The alpha1-adrenergic agonist, phenylephrine and the beta2
      adrenergic agonist isoproterenol were studied in 10 Native American and White
      volunteers. The dorsal hand vein technique was used, which is a simple,
      relatively non-invasive method to study the response to vasoactive substances, in
      vivo. RESULTS: The maximal venodilatory response to isoproterenol in the Native
      American group was 53.2+/-27.5%; while in the White group it was 103.4+/-66.0%
      (p<0.05). The maximal venoconstriction for phenylephrine in the Native American
      subject group was similar to that of the White group (85.4+/-24.0% vs. 89.4+/
      10.9%) (p = n.s.). CONCLUSIONS: Based on our findings, we can anticipate that
      Native Americans may respond differently to antihypertensive therapy. However,
      further investigation needs to be done with an eye towards the development of
      drug therapy and treatment strategies tailored to this specific population.

PMID- 10204663
TI  - Atherosclerosis in amputated legs of patients with and without diabetes mellitus.
AB  - BACKGROUND: The aim of this study was to compare the histomorphologic appearance
      of atherosclerosis in amputated legs of diabetic and non-diabetic patients.
      METHODS: Twenty-eight legs amputated below the knee for chronic ischaemia were
      studied. Fourteen legs were amputated in patients with diabetes (10 Type II, 4
      nonclassified) and 14 in non-diabetics. The mean age of patients at the time of
      the amputation was 63.3 years in diabetics and 63.9 years in non-diabetics.
      Samples were taken from the main arteries at the following levels: the midleg, 5
      cm above the ankle, 3 cm below the ankle and 10 cm below the ankle. Cross
      sections of the arteries were examined with light microscopy and the severity of
      the occlusive disease determined using morphometric analysis. Medial
      calcification and chronic inflammation were assessed semiquantitatively. RESULTS:
      Arteries at 5 cm above the ankle were more severely stenotic in diabetics than in
      non-diabetics (p<0.05). In both diabetics and non-diabetics the posterior tibial
      and plantar arteries appeared to be the most stenotic. Medial calcification
      tended to be more prominent in diabetics than in non-diabetics. Chronic
      inflammation in the arterial wall occurred at the same degree in diabetics and
      non-diabetics. In non-diabetics chronic inflammation was more severe in the
      posterior tibial and plantar arteries than in the anterior tibial and dorsalis
      pedis arteries (p<0.04). Chronic arterial inflammation correlated with the
      severity of chronic arterial occlusive disease (p<0.0002). CONCLUSIONS: In
      diabetics occlusive disease in amputated legs is more severe in arteries above
      the ankle than in non-diabetics. However, no difference was demonstrated in this
      series in arteries of the ankle and foot. Diabetics are likely to have more
      medial calcification in the arteries than non-diabetics. Chronic inflammation in
      the arterial wall is associated with more severe stenosis.

PMID- 10204664
TI  - Biomarkers in the identification of risks, especially with regard to susceptible
      persons and subgroups.

PMID- 10204665
TI  - Lymphatic and hematopoietic cancer in teachers.
AB  - A recent study found high rates of leukemia and related disorders among teachers.
      This finding may be related to exposure to childhood infections. Therefore,
      epidemiologic studies on the risk of lymphatic and hematopoietic cancer among
      teachers were systematically reviewed. Altogether 26 relevant investigations were
      identified, most from ad hoc publications rather than from scientific journals.
      Elevated risks of leukemia, lymphoma, and multiple myeloma were found in studies
      using proportional mortality or mortality odds ratios as outcome measures.
      However, these observations may reflect low overall mortality and do not
      necessarily indicate high death rates from the cancers of interest. In studies
      deriving standardized mortality or incidence ratios, the risk estimates were
      generally lower. The most striking finding was for non-Hodgkin's lymphoma
      (approximate summary relative risk 1.36, 95% confidence interval 1.13-1.62), but
      it was likely to have been exaggerated by publication bias. In conclusion, no
      compelling epidemiologic evidence exists for a hazard of leukemia or related
      diseases among teachers.

PMID- 10204666
TI  - Magnetic resonance appearance of asbestos-related benign and malignant pleural
      diseases.
AB  - OBJECTIVES: This study describes the magnetic resonance findings of benign and
      malignant pleural diseases in asbestos-exposed subjects. METHODS: Thirty patients
      with a history of asbestos exposure and pleural lesions in chest X-rays and
      computed tomography scans were examined with a 0.5- and a 1.5-T magnetic
      resonance unit. The examination protocol included cardiac-gated proton density
      and T2-weighted images, unenhanced and enhanced (Gd-DTPA; 0.1 mmol/ kg) T1
      weighted images in the axial plane and sometimes in another orthogonal plane
      (sagittal or coronal or both). All the magnetic resonance images were reviewed by
      3 experienced observers, who visually evaluated morphologic features, signal
      intensity, and contrast enhancement of pleural lesions. The diagnosis was
      established by means of percutaneous biopsy, thoracotomy, and combined clinical
      and radiological follow-up for at least 3 years. RESULTS: Eighteen patients
      affected with multiple pleural plaques showed low signal intensity on both
      unenhanced and enhanced T1-weighted and proton density and T2-weighted images. In
      2 of these patients an acute pleural effusion was observed. All the malignant
      lesions (11 mesotheliomas) and a solitary benign pleural plaque revealed high
      signal intensity on the proton density and T2-weighted images and inhomogeneous
      contrast enhancement in the postcontrast T1-weighted images. The sensitivity,
      specificity, and diagnostic accuracy of the magnetic resonance imaging in
      classifying a lesion as suggestive of malignancy were 100%, 95% and 97%,
      respectively. CONCLUSIONS: The results point out 2 magnetic resonance signal
      intensity patterns for asbestos-related pleural lesions: (i) low-signal intensity
      on unenhanced and enhanced T1-weighted and proton density and T2-weighted images
      for benign plaques and (ii) nonhomogeneous hyperintensity in T2-weighted and
      enhanced T1-weighted images for malignant mesotheliomas.

PMID- 10204667
TI  - Genotoxic exposures of potroom workers.
AB  - OBJECTIVES: Potroom workers in aluminum reduction plants have increased risks for
      bladder and lung cancer due to exposure from polycyclic aromatic hydrocarbons
      (PAH). In this study correlations between measures of the external, internal, and
      biological effective dose have been studied for PAH. METHODS: Venous blood
      samples were obtained from 98 male potroom workers and 55 unexposed male blue
      collar workers, for the analysis of aromatic adducts to DNA (deoxyribonucleic
      acid) in lymphocytes, using the 32P-postlabeling technique. 1-Hydroxypyrene in
      urine was analyzed with high-pressure liquid chromatography. Personal sampling of
      both particulate and gas phase PAH was performed during a full workday for the
      potroom workers and for 5 referents. Individual PAH congeners were determined
      with liquid chromatographic-mass spectrometric and gas chromatographic-mass
      spectrometric techniques. RESULTS: The respiratory-zone airborne level of the sum
      of 22 particulate (median 13.2 micro/m3) and the 7 gas phase PAH-congeners
      (median 16.3 microg/m3) among the potroom workers was a hundred times higher than
      among the referents. The urinary concentration of 1-hydroxypyrene before work was
      30 times higher for the potroom workers (median 3.43 micromol/mol creatinine)
      than for the referents. Most airborne PAH congeners correlated with the excretion
      of 1-hydroxypyrene in urine. The frequency of aromatic DNA adducts did not,
      however, differ between the potroom workers and the referents, and no correlation
      was found for 1-hydroxypyrene in urine. CONCLUSIONS: Despite an obvious
      occupational exposure to PAH, no increase in aromatic DNA adducts in lymphocytes
      was found among the potroom workers.

PMID- 10204668
TI  - Exposure of farmers to phosmet, a swine insecticide.
AB  - OBJECTIVES: The goal of this study was to measure dermal and inhalation exposures
      to phosmet during application to animals and to identify what determinants of
      exposure influence the exposure levels. METHODS: Ten farmers were monitored using
      dermal patches, gloves, and air sampling media during normal activities of
      applying phosmet to pigs for insect control. Exposures were measured on the
      clothing (outer), under the clothing (inner), on the hands, and in the air.
      Possible exposure determinants were identified, and a questionnaire on work
      practices was administered. RESULTS: The geometric mean of the outer exposure
      measurements was 79 microg/h, whereas the geometric mean of the inner exposure
      measurements was 6 microg/h. The geometric mean for hand exposure was 534
      microg/h, and the mean air concentration was 0.2 microg/m3. Glove use was
      associated with the hand and total dermal exposure levels, but no other
      determinant was associated with any of the exposure measures. The average
      penetration through the clothing was 54%, which dropped to 8% when the farmers
      wearing short sleeves were excluded. The farmers reported an average of 40 hours
      a year performing insecticide-related tasks. CONCLUSIONS: Farmers who applied
      phosmet to animals had measurable exposures, but the levels were lower than what
      has been seen in other pesticide applications. Inhalation exposures were
      insignificant when compared with dermal exposures, which came primarily from the
      hands. Clothing, particularly gloves, provided substantial protection from
      exposures. No other exposure determinant was identified.

PMID- 10204669
TI  - Increase in interleukin-6 and fibrinogen in peripheral blood after swine dust
      inhalation.
AB  - OBJECTIVES: The inhalation of dust from swine confinement buildings causes
      inflammatory responses in the airways with a rise of interleukin-6 (IL-6). The
      purpose of this study was to confirm the increase in serum IL-6 after inhalation
      of swine dust and investigate a possible increase in plasma fibrinogen. METHODS:
      Eight healthy nonsmoking volunteers inhaled dust for 4 hours inside a swine
      confinement building. Inhalable dust and endotoxin were sampled. The
      concentrations of IL-6 and fibrinogen were determined in serum and plasma.
      RESULTS: The study showed a clear increase in the concentrations of IL-6 and
      fibrinogen after exposure. CONCLUSIONS: As fibrinogen is an important risk factor
      for ischemic heart disease, the increased concentration of fibrinogen among
      persons exposed to swine dust may increase the risk for this disease.

PMID- 10204670
TI  - Predictors and consequences of unemployment in construction and forest work
      during a 5-year follow-up.
AB  - OBJECTIVES: The study investigated whether indicators of health, work conditions,
      or life-style predict subsequent unemployment and also the unemployment
      consequences related to health or life-style. METHODS: A questionnaire was
      administered to 781 male construction and 877 male forest workers (aged 20-49
      years and working at the beginning of the study) in 1989 and 1994. Employment
      status during follow-up was ranked into the following 4 categories according to
      the employment status and unemployment time: continuously employed, re-employed,
      short-term (< or = 24 months) unemployed and long-term (> or =24 months)
      unemployed. RESULTS: The following base-line factors were associated with long
      term unemployment during follow-up among the construction workers: age >40 years,
      poor subjective health, smoking, frequent heavy use of alcohol, low job
      satisfaction, marital status (single), and unemployment during the year preceding
      the initial survey. Among the forest workers, age >40 years, frequent stress
      symptoms, and preceding unemployment entered the model. In addition smoking
      predicted unemployment among the forest workers with no preceding unemployment.
      The proportion of regular smokers decreased among the long-term unemployed.
      Physical exercise was more frequent at the time of follow-up than it was
      initially, particularly among the unemployed. Stress symptoms increased among the
      construction workers, but musculoskeletal symptoms decreased significantly among
      the long-term unemployed. Among the forest workers stress symptoms decreased
      among the continuously employed and re-employed persons, but musculoskeletal
      symptoms decreased significantly for them all. CONCLUSIONS: Unemployment among
      construction workers is to some extent dependent on life-style, health, and job
      satisfaction in addition to age, marital status, and unemployment history. For
      forest workers, unemployment is less determined by individual factors. Changes in
      distress and musculoskeletal symptoms are dependent on employment, particularly
      among construction workers.

PMID- 10204671
TI  - Prognostic factors for chronic disability from acute low-back pain in
      occupational health care.
AB  - OBJECTIVES: This study attempted to determine the prognostic indicators of low
      back pain in an occupational health setting. METHODS: The identification of
      prognostic factors of (i) functional disability after 3 months' follow-up, (ii)
      functional disability after 12 months' follow-up, and (iii) time to return to
      work among 120 workers who reported to an occupational health unit and were off
      work with low-back pain for at least 10 days. Crude and adjusted odds ratios and
      hazard ratios with 95% confidence intervals were estimated for the 3 outcome
      measures. RESULTS: Factors related to a longer time to return to work were
      radiating pain, high functional disability at the beginning of the study,
      problems in relations with colleagues, and high work tempo and work quantity.
      High functional disability at the beginning of the study and a high avoidance
      coping style predicted functional disability at 3 months. Functional disability
      at 12 months was more accurately predicted by work-related and psychosocial
      factors. CONCLUSIONS: Especially radiating pain and functional disability predict
      a long duration of low-back pain in occupational health practice. Occupational
      physicians should also note work-related and psychosocial characteristics.

PMID- 10204672
TI  - Interindividual variation of physical load in a work task.
AB  - OBJECTIVES: This study analyzed the variation in physical work load among
      subjects performing an identical work task. METHODS: Electromyographs from the
      trapezius and infraspinatus muscles and wrist movements were recorded bilaterally
      from 49 women during a highly repetitive industrial work task. An interview and a
      physical examination were used to define 12 potential explanatory factors,
      namely, age, anthropometric measures, muscle strength, work stress, and
      musculoskeletal disorders. RESULTS: For the electromyographs, the means of the
      10th percentiles were 2.2% and 2.8% of the maximal voluntary electrical activity
      (%MVE) for the trapezius and infraspinatus muscles, respectively. However, the
      interindividual variations were very large [coefficients of variation (CV) 0.75
      and 0.62, respectively]. Most of the variance could not be explained; only
      height, strength, and coactivation of the 2 muscles contributed significantly
      (R2(adj)0.20-0.52). The variation was still large, though smaller (CV < or
      =0.63), for values normalized to relative voluntary electrical activity (RVE).
      For the wrist movements, the median velocity was 29 degrees per second, and the
      interindividual variations were small (CV < or =0.24). Six factors contributed to
      the explained variance (R2(adj)0.12-0.55). CONCLUSIONS: The interindividual
      variation is small for wrist movements when the same work tasks are performed. In
      contrast, the electromyographic variation is large, even though less after RVE
      normalization, which reduces the influence of strength, than when MVE is used.
      Because of these variations, several electromyographs are needed to characterize
      the exposure of a specific work task in terms of muscular load, and individual
      electromyographs are preferable when the worker' s risk of myalgia is being
      studied.

PMID- 10204673
TI  - Functional and high-resolution computed tomographic studies of divers' lungs.
AB  - OBJECTIVES: Several cross-sectional studies have described a decrease in the
      expiratory flow rates of divers. The objective of this study was to determine
      whether the combined application of high-resolution computed tomography (HRCT)
      and lung function testing supports the reported development of small airway
      obstruction in divers. METHODS: Thirty-two navy divers, 27 commercial divers, and
      48 referents matched for age and smoking history underwent pulmonary function
      testing and HRCT of the lungs supplemented by a limited number of expiratory
      scans. The commercial divers were older and dived longer than the navy divers.
      Multivariate regression analysis was used to assess the relevant correlations of
      age, height, pack-years of cigarette smoking, and indices of diving exposure with
      lung function parameters. RESULTS: The inspiratory vital capacity and forced
      vital capacity (FVC) were greater, while the FEV% [(100 x FEV10)FVC] and maximum
      expiratory flow (MEF) at 25% (MEF25) of the FVC were lower for the navy divers
      than for the referents. The lung volumes and expiratory airflow pattern did not
      differ between the commercial divers and the corresponding referents. The forced
      expiratory volume in 1 second (FEV10), FEV%, MEF75, and MEF25 correlated
      negatively with the years of diving experience. This association was independent
      of age, height, and pack-years of cigarette smoking. For the majority of the
      divers and referents the expiratory HRCT revealed minor lobular air trapping
      without any difference between the groups. The HRCT did not show relevant
      morphologic abnormalities of small or large airways. CONCLUSIONS: The data
      confirm that diving may affect pulmonary function. However, there is no
      radiologic evidence for the development of small airway disease in these 2
      subgroups of divers.

PMID- 10204674
TI  - The thyrotrophin-releasing hormone analogue MK771 induces tic-like behaviours:
      the effects of dopamine D1 and D2 receptor antagonists.
AB  - Thyrotrophin-releasing hormone (TRH) and its analogues induce tic-like behaviours
      in rodents such as blinking and forepaw licking. Changes in spontaneous blinking
      frequency are observed in several disease states with dopamine abnormalities and
      dopaminergic agents modulate blinking. We have therefore investigated the effects
      of dopamine D1 and D2 receptor antagonists on TRH analogue (1-pyro-2-aminoadipyl
      L-histidyl-L-thiazolidine-4-carboxamide; MK771)-induced blinking and bouts of
      forepaw licking. MK771 (2.5 mg/kg)-induced blinking was not attenuated by the
      dopamine D1 receptor antagonists (+)-7-chloro-hydroxy-3-methyl-1-phenyl-2,3,4,5
      tetrahydro(1H)-3-benzazep ine maleate (SCH23390) (0.01, 1.0 and 5.0 mg/kg) and ((
      )-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5- H
      benz[2,1b]azepine (SCH39166; 1.0 and 5.0 mg/kg) or the dopamine D2 receptor
      antagonists raclopride (3.0 and 5.0 mg/kg) and sulpiride (5.0 and 10.0 mg/kg). D1
      but not D2 receptor antagonists attenuated MK771-induced forepaw licking. MK771
      induced blinking, therefore, appears not to involve dopamine D1 or D2 receptors
      and contrary to previously held belief dopamine does not appear to be pivotal in
      the control of blinking, while MK771-induced forepaw licking is modulated by
      dopamine D1 but not D2 receptors.

PMID- 10204675
TI  - Selective melanocortin MC4 receptor blockage reduces immobilization stress
      induced anorexia in rats.
AB  - We investigated the effects of selective melanocortin MC4 receptor blockage on
      immobilization stress-induced anorexia. Male rats were subjected to
      immobilization once a day for 4 days. Prior to each of the stress treatments, the
      rats were injected i.c.v. (intracerebroventricularly) with either saline or the
      melanocortin MC4 receptor antagonist HS014 (cyclic [AcCys11, D-Nal14, Cys18, Asp
      (NH22)2]beta-MSH-(11-22) (melanocyte-stimulating hormone). Rats subjected to
      neither stress nor i.c.v. injections served as controls. The results showed that
      the cumulative food intake and body weight gain in the stressed group treated
      with HS014 was significantly higher than in the stressed group and significantly
      lower than in the control group. Repeated injections of the melanocortin MC4
      receptor antagonist were effective and there were no signs of tachyphylaxis. This
      is the first report showing that melanocortin MC4 receptor blockage can relieve
      an anorectic condition, which may indicate that melanocortin MC4 receptor
      blockage is an effective way to treat anorectic disorders.

PMID- 10204676
TI  - Effects of adenosine receptor agents on the expression of morphine withdrawal in
      mice.
AB  - Effects of different doses of adenosine receptor agonists and antagonists on
      naloxone-induced jumping and diarrhea in morphine-dependent mice were studied.
      The adenosine A1 receptor agonists, N6-cyclohexyladenosine (CHA: 0.1, 0.25 and
      0.5 mg kg(-1)) and R-isomer of N6-phenylisopropyladenosine (R-PIA: 0.1, 0.3 and 1
      mg kg(-1)), decreased jumping and diarrhea induced by naloxone in morphine
      dependent mice. The adenosine A1 receptor antagonist, 8-cyclopentyl-1,3
      dipropylxanthine (DPCPX: 0.3-9 mg kg(-1)), increased jumping but decreased
      diarrhea. The adenosine A2 receptor agonist, 5'-(N-cyclopropyl)
      carboxamidoadenosine (CPCA), decreased jumping and diarrhea. However, the
      adenosine A2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX: 0.5 and
      1 mg kg(-1)), did not elicit any response in this respect. DPCPX (0.3 and 3 mg
      kg(-1)), decreased the inhibition of jumping and diarrhea induced by CHA (0.5 mg
      kg(-1)), while DMPX (0.5 and 1 mg kg(-1)), decreased the inhibition of diarrhea
      induced by CPCA (0.1 mg kg(-1)). It is concluded that jumping induced by naloxone
      in morphine-dependent mice may be modified by the adenosine A receptor
      mechanism(s) and diarrhea induced by the opioid receptor antagonist could be
      mediated by the adenosine A1 and A2 receptors.

PMID- 10204677
TI  - Effects of ginseng saponins on responses induced by various receptor stimuli.
AB  - We investigated the effects of four ginseng saponins, ginsenoside-Rb1, -Rg2, -Rg3
      and -Ro, on the responses induced by receptor stimulation of various stimuli.
      Ginsenoside-Rg2 (1-100 microM) reduced the secretions of catecholamines from
      bovine adrenal chromaffin cells stimulated by acetylcholine and gamma
      aminobutyric acid but not by angiotensin II, bradykinin, histamine and
      neurotensin. In guinea-pig, the ginsenoside also diminished the nicotine-induced
      secretion of catecholamines from the adrenal chromaffin cells, but it did not
      affect the muscarine- and the histamine-induced ileum contractions. On the other
      hand, ginsenoside-Rg3 (1-100 microM) reduced not only the acetylcholine-, the
      gamma-aminobutyric acid- and the neurotensin-induced secretions but also, at a
      higher concentration (100 microM), the angiotensin II-, the bradykinin- and the
      histamine-induced secretions from the bovine chromaffin cells. Furthermore, the
      saponin (3-100 microM) significantly inhibited the muscarine- and the histamine
      induced ileum contractions of the guinea-pig. Ginsenoside-Rb1 and -Ro had no
      marked effect on their responses. These results strongly suggest that ginsenoside
      Rg2 is a potent selective blocker of nicotinic acetylcholine and gamma
      aminobutyric acid receptors (ionotropic receptors) and ginsenoside-Rg3 is not
      only a blocker of ionotropic receptors but also an antagonist of muscarinic or
      histamine receptors.

PMID- 10204678
TI  - Antagonism of GABA(B) receptors by morpholino-2-acetic acid derivatives Sch 54679
      and Sch 51324 in rat brain.
AB  - In rat neocortical slices maintained in Mg2+-free Krebs medium, baclofen
      depressed the rate of spontaneous discharges in a concentration-dependent manner
      (EC50 = 4.5 microM). This depression was reversibly antagonised by 5-(S,R)
      hydroxymethyl-5-methylmorpholinyl-2-(R,S)-acetic acid (Sch 54679) and 2-(R,S)-5
      [spirocyclopentyl]-morpholinyl-acetic acid (Sch 51324) (respective pA2 values of
      5.8+/-0.15 and 5.4+/-0.2). In electrically-stimulated slices preloaded with
      [3H]gamma-aminobutyric acid (GABA), Sch 54679 (EC50 = 3 microM) was 2.3 times
      more potent than Sch 51324 (EC50 = 7 microM) in increasing [3H]GABA release
      through antagonism of GABA(B) autoreceptors. These structurally novel analogues
      may be pharmacologically useful for elucidating GABA(B) receptor functions.

PMID- 10204679
TI  - Role of endogenous adenosine in the expression of opiate withdrawal in rats.
AB  - Samples of extracellular fluid from striatum and nucleus accumbens of
      anaesthetised rats undergoing opiate withdrawal were collected using
      microdialysis and then analysed for adenosine and its metabolites using high
      performance liquid chromatography (HPLC) and ultraviolet (UV) detection. Although
      the amount of adenosine present in the dialysate from either brain region was
      below the limit of detection by 90 min after probe placement, the metabolites
      could still be detected. Samples of dialysates collected from the nucleus
      accumbens contained significantly higher concentrations of hypoxanthine and
      inosine following naloxone challenge. The data are compatible with the hypothesis
      that endogenous adenosine might be involved in the expression of the opiate
      abstinence syndrome.

PMID- 10204680
TI  - Stereoselective and endothelium-independent action of nicardipine on the isolated
      porcine coronary artery.
AB  - The qualitative and quantitative effects of the (+)-S and (-)-R enantiomers and
      of the racemic mixture of the Ca2+ channel antagonist, nicardipine, were compared
      on the isolated porcine coronary artery with intact and removed endothelium. All
      three forms of nicardipine inhibited the contractions induced by KCl (5-90 mM) in
      both vessel preparations. The potency (IC50) of the (+)-S and (-)-R enantiomers
      and of the racemic mixture was 6.6, 31.8 and 10.9 nM in the vessel with
      endothelium and 6.4, 41.9 and 9.8 nM in the vessel without endothelium. The
      parameters of the concentration-response curves for each form of nicardipine at a
      submaximal KCl (60 mM) concentration and the potency ratios between the two
      enantiomers ((+)-S/(-)-R) were not statistically significantly different (P>0.05)
      in the two vessel preparations. In conclusion, qualitatively, all three forms of
      nicardipine showed only Ca2+ channel antagonistic effects in both vessel
      preparations. Quantitatively, the inhibition of contraction was stereoselective,
      the (+)-S enantiomer being the most potent, and was endothelium-independent.

PMID- 10204681
TI  - The lazaroid, U-74389G, inhibits inducible nitric oxide synthase activity,
      reverses vascular failure and protects against endotoxin shock.
AB  - The aim of our study was to investigate the effect of the 21-aminosteroid U
      74389G [21- < 4-(2,6-di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl-pregna
      1,4,9,(11) triene-3,20-dione(z)-2-butenedionate] on the l-arginine-nitric oxide
      (NO) pathway in a rat model of endotoxin shock. Endotoxin shock was produced in
      male rats by a single intravenous (i.v.) injection of 20 mg/kg of Salmonella
      Enteritidis lipopolysaccharide (LPS). Rats were treated with U-74389G (7.5, 15
      and 30 mg/kg i.v.) or vehicle (1 ml/kg i.v.) 5 min after endotoxin challenge.
      Lipopolysaccharide administration reduced survival rate (0%, 72 h after endotoxin
      administration) decreased mean arterial blood pressure, enhanced plasma
      concentration of bilirubin and alanine aminotransferase and increased plasma
      nitrite concentrations. Lipopolysaccharide injection also increased the activity
      of inducible NO synthase in the liver and in the aorta. Furthermore aortic rings
      from shocked rats showed a marked hyporeactivity to phenylephrine (1 nM-10
      microM). In addition lipopolysaccharide (50 microg/ml for 4 h) in vitro
      stimulation significantly increased nitrite production in peritoneal macrophages
      harvested from normal rats. Treatment with U-74389G (15 and 30 mg/kg i.v., 5 min
      after endotoxin challenge) significantly protected against lipopolysaccharide
      induced lethality (90% survival rate 24 h and 80% 72 h after lipopolysaccharide
      injection, respectively, following the highest dose of the drug), reduced
      hypotension, ameliorated liver function, decreased plasma nitrite levels,
      restored the hyporeactivity of aortic rings to their control values and inhibited
      the activity of inducible NO synthase in the liver and in the aorta. Finally, U
      74389G in vitro (12.5, 25 and 50 microM) significantly inhibited nitrite
      production in endotoxin stimulated peritoneal macrophages. The data suggest that
      U-74389G may exert beneficial effects in an experimental model of septic shock by
      inhibiting the activity of the inducible NO synthase.

PMID- 10204682
TI  - Effects of class III antiarrhythmic agents in an in vitro rabbit model of
      spontaneous torsades de pointe.
AB  - Acquired long QT syndrome develops as a result of pharmacological interventions
      that prolong action potential duration. Excessive action potential prolongation
      may lead to torsade de pointes, a potentially fatal arrhythmia. To study this
      arrhythmia, in vivo models have been developed, but are difficult to interpret
      due to the complex nature of the intact metabolic, nervous and humoral systems.
      To more clearly examine the propensity of various Class III agents to elicit
      torsades de pointe, an in vitro model of spontaneous torsades de pointe was used
      in isolated perfused rabbit hearts. Male New Zealand white rabbits were
      anesthetized with sodium pentobarbital, and hearts isolated and perfused in a
      Langendorff apparatus. Electrocardiogram and epicardial monophasic action
      potentials were continuously recorded, and methoxamine (30 nM) and acetylcholine
      (0.3 microM) were given throughout the experiment. After 10 min of methoxamine
      and acetylcholine perfusion, Class III agents, dofetilide (0.1 to 0.7 microM), E
      4031 (0.1 to 0.5 microM), D-sotalol (10 to 30 microM), or clofilium (0.1 to 0.3
      microM), were given. All agents, except D-sotalol, induced torsades de pointe in
      100% of hearts tested. D-Sotalol (30 microM) elicited a low incidence of torsades
      de pointe (25%). This could be explained by the limited prolongation of action
      potential duration with D-sotalol as compared to other Class III agents under
      these conditions. Dofetilide, a selective Class III agent, alone did not induce
      torsades de pointe. Nadolol (3 microM), a beta-adrenoceptor antagonist, increased
      the propensity of dofetilide to elicit torsades de pointe. In conclusion,
      increases in action potential duration (i.e., using Class III agents) in
      combination with a low heart rate (muscarinic receptor stimulation) and increases
      in intracellular Ca2+ (alpha-adrenoceptor stimulation) are needed to develop
      torsades de pointe in this model. Modulating these systems may provide us with
      new insights into preventing the initiation or maintenance of this arrhythmia.

PMID- 10204683
TI  - Acute intracranial hypertension-induced inhibition of gastric emptying:
      evaluation in conscious rats.
AB  - To study the effect of raised intracranial pressure (ICP)-induced alterations in
      gastric emptying, and their modulation by pharmacological interventions, an
      experimental model was standardized in rats. A test meal of methylcellulose and
      phenol red was administered intragastrically. ICP was raised to 40, 60 and 80
      mmHg by connecting a buffered saline pressure head to an intracerebroventricular
      (i.c.v.) cannula. Gastric emptying was estimated after killing the animals, from
      the residual stomach phenol red content. Inhibition of gastric emptying was
      observed when ICP was raised, the maximum being at 80 mmHg ICP (percent gastric
      emptying 26.5%+/-2.8 vs. 83.4+/-4.7 in sham-ICP). Pretreatment with clonidine,
      prazosin or ondansetron did not modify the raised ICP-induced inhibition of
      gastric emptying. Cisapride was ineffective at 1 mg/kg but caused a partial
      reversal at the 5- and 10-mg/kg doses (46.9+/-3.1% and 42.6+/-4.0%,
      respectively). Carbachol at a lower dose of 0.1 mg/kg i.p., produced a greater
      reversal (78.3+/-6.0%) than did the high dose (52.8+/-4.1). Bretylium partially
      reversed the inhibition of gastric emptying (45.7+/-4.3%). The protective effect
      of carbachol and cisapride suggests that suppression of vagal activity due to
      increased ICP may play an important role in the inhibition of gastric emptying
      due to intracranial hyper-tension.

PMID- 10204684
TI  - Characterization of neurotensin receptors in intestinal smooth muscle using a
      nonpeptide antagonist.
AB  - Neurotensin reduced substance P-induced tension in ileal muscle strips and the
      relaxant effect was inhibited by a nonpeptide antagonist, SR 48692, 2-[(1-(7
      chloro-4-quinolinyl)-5-(2,6-dimethoxyphenyl)pyrazol-3-yl)car
      bonylamino]tricyclo(3.3.1.1.(3.7)decan-2-carboxylic acid with a half-maximal
      concentration (IC50) of 7.4+/-2.1 nM (n = 9) and a dissociation constant (Kb) of
      0.9+/-0.2 nM. Neurotensin produced a contractile response in ileal muscle strips
      pretreated with apamin (50 nM) and in isolated chick rectums and both contractile
      effects were inhibited by SR 48692 with IC50 of 31.6+/-9.5 nM and Kh of 3.2+/-0.9
      nM (n = 6) and with IC50 of 28.9+/-6.9 nM and Kb of 5.4+/-1.0 nM (n = 7),
      respectively. The Kb values for the contractile effects were not significantly
      different from each other, but significantly different from that for the relaxant
      effect, suggesting that both types of effect are mediated via distinct subtypes
      of neurotensin receptor in the intestinal smooth muscles. Contractile responses
      and excitatory junction potentials evoked by electrical stimulation of
      nonadrenergic, noncholinergic (NANC) nerves in isolated chick rectums were not
      inhibited by SR 48692 (up to 3.3 microM). This does not provide functional
      evidence for the idea that neurotensin acts as an unidentified excitatory
      neurotransmitter of NANC nerves in the avian rectum.

PMID- 10204686
TI  - Lack of evidence for tachykinin NK1 receptor-mediated neutrophil accumulation in
      the rat cutaneous microvasculature by thermal injury.
AB  - The effect of the non-peptide selective tachykinin NK1 receptor antagonist
      SR140333 has been investigated on oedema formation and neutrophil accumulation
      induced by thermal injury (50 degrees C for 5 min), mustard oil, substance P, the
      tachykinin NK1 agonist GR73632, and interleukin-1beta in the abdominal skin of
      the anaesthetised rat. SR140333 significantly inhibited (120 nmol/kg i.v.) or
      prevented (240 nmol/kg i.v.) the early oedema formation (0-10 min) induced by
      thermal injury. However, a dosing strategy which blocked NK1 receptors for 5 h
      (SR140333, 240 nmol/kg i.v. + 240 nmol/kg s.c.) failed to influence neutrophil
      accumulation measured 5 h after thermal injury. Thus, the neurogenic component
      mediated by NK1 receptors is important to elicit the early oedema formation, but
      does not influence subsequent neutrophil accumulation. Topical application of
      mustard oil (2%), a neurogenic inflammation stimulant, caused NK1 receptor
      mediated early neurogenic plasma extravasation, but did not induce cutaneous
      neutrophil accumulation over 5 h. Substance P and GR73632 at high doses (1
      nmol/site) also failed to elicit neutrophil accumulation. Neutrophil accumulation
      induced by interleukin-1beta (0.03-3 pmol i.d.) was not affected by SR140333
      pretreatment. In conclusion, despite an early pronounced tachykinin NK1 receptor
      dependent oedema response after thermal injury, the results suggest that
      subsequent neutrophil accumulation is not mediated by NK1 receptors. Furthermore,
      we have not obtained any evidence to suggest that either endogenous or exogenous
      tachykinins can directly induce neutrophil accumulation in the rat cutaneous
      microvasculature.

PMID- 10204685
TI  - Characterization of antisecretory and antiulcer activity of CR 2945, a new potent
      and selective gastrin/CCK(B) receptor antagonist.
AB  - The antigastrinic, antisecretory and antiulcer activities of CR 2945, (R)-1
      naphthalenepropanoic acid,beta-[2-[[2-(8-azaspiro[4.5]dec-8-yl-carbonyl)-4,6
      dimethylph enyl] amino]-2-oxoethyl], were investigated in vitro and in vivo in
      rats and cats. Its activities were compared with those of two gastrin/CCK(B)
      receptor antagonists, L-365,260 (3R(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H
      1,4-benzodiazepin -3-yl)-N'-(3-methylphenyl)urea and CAM-1028 (4-[[2-[[3-(1H
      indol-3-yl)-2-methyl-1-oxo-2-[[[1,7,7-trimethylbicyclo [2.2.1]hept-2
      yl)oxy]carbonyl]amino]propyl]amino]-1-phenylethyl]amino -4-oxo-[1S
      1alpha,2beta[S'(S')4alpha]]-butanoate -N-methyl-D-glucamine), of the histamine H2
      receptor antagonist, ranitidine, and the proton pump inhibitor, omeprazole.
      Cytosolic Ca2+ elevation in rabbit parietal cells induced by gastrin (50 nM) was
      blocked by CR 2945 with an IC50 value of 5.9 nM. CAM-1028 and L-365,260 showed
      similar activity. CR 2945 antagonized pentagastrin-stimulated gastric acid
      secretion in rats (ED50 = 1.3 mg kg(-1) i.v. and 2.7 mg kg(-1) i.d.) and cats
      (1.6 mg kg(-1) i.v.). CR 2945 was slightly less potent than the reference
      compounds after i.v. administration, whereas after intraduodenal (i.d.)
      administration, it was more potent than both ranitidine and omeprazole. In the
      rat, the gastrin antagonism exhibited by CR 2945 was reversible and competitive,
      with a pA2 value of 7.33. CR 2945 had specific antigastrin activity, as it was
      unable to antagonize the gastric acid secretion stimulated by histamine or
      carbachol in rats up to the dose of 30 mg kg(-1). CR 2945 was about as
      efficacious as ranitidine against the indomethacin- and ethanol-induced gastric
      ulcers and the cysteamine-induced duodenal ulcer in rats. On the contrary, L
      365,260 was only slightly effective. These results suggest that CR 2945 might be
      a promising compound for the therapy of acid-related disorders, and that its
      clinical use could help clarify the therapeutic potential of gastrin/CCK(B)
      receptor antagonists in the gut.

PMID- 10204687
TI  - Effect of dexamethasone on cyclophosphamide-induced cystitis in rats: lack of
      relation with bradykinin B1 receptor-mediated motor responses.
AB  - We investigated the role of bradykinin B receptors in inducing urinary bladder
      contraction and maintaining bladder compliance in anaesthetized rats following
      cyclophosphamide-induced bladder inflammation and the influence of dexamethasone
      treatment on these responses. In the group treated with cyclophosphamide the
      amplitude of the contraction induced by the selective bradykinin B1 receptor
      agonist des-Arg9-bradykinin was larger than that in controls and dexamethasone
      prevented the up-regulation of this response induced by inflammation. The
      specific binding of [3H]des-Arg10-kallidin to bladder membranes was only detected
      in cyclophosphamide-treated rats: this binding was prevented by dexamethasone
      pretreatment. The bladder contraction induced by des-Arg9-bradykinin in
      cyclophosphamide-treated rats was antagonized by the bradykinin B1 receptor
      antagonist des-Arg9-D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]bradykinin (des-Arg10-Hoe 140).
      Cyclophosphamide treatment increased the bladder weight and dexamethasone
      reversed this effect. Bladder compliance was decreased in the bladder
      inflammation group and this effect was partially reversed by dexamethasone
      pretreatment. Neither des-Arg10-Hoe 140 nor the combined administration of des
      Arg10Hoe 140 and the selective bradykinin B2 receptor antagonist D-Arg
      [Hyp3,Thi5,D-Tic7,Oic8]bradykinin (Hoe 140) affected bladder compliance, thus
      excluding a role of kinins in the maintenance of bladder tone during
      inflammation. These results indicate that: (1) dexamethasone pretreatment
      ameliorates cyclophosphamide-induced bladder inflammation: (2) dexamethasone
      pretreatment prevents cyclophosphamide-induced up-regulation of bradykinin B
      receptors; (3) kinins do not contribute to the increased vesical tone during
      inflammation.

PMID- 10204688
TI  - Ca2+ response of rat mesangial cells to ATP analogues.
AB  - The aim of this investigation was to characterise the effects of ATP analogues
      and UTP on the single cell intracellular Ca2+ concentration ([Ca2+]i) in cultured
      rat mesangial cells. Typically, there were two phases in the Ca2+ response to the
      agonists, an initial fast transient peak and a subsequent slower decline, or
      plateau, phase. For the peak amplitude in [Ca2+]i the agonists had about equal
      effect. But when taking in consideration the percentage of responding cells and
      the integrated Ca2+ response over 1 min, the order of efficacy of nucleotide
      agonists (100 microM) was UTP = ATP > ATPgammaS > ADP = 2MeS-ATP (2-methylthio
      ATP). Adenosine, AMP and beta,gamma-Me-ATP (100 microM) had no effect. Suramine
      (100 microM) and reactive blue (50 microM) decreased the number of responding
      cells. Removing Ca2+ from the bath diminished neither the peak in [Ca2+]i nor the
      percentage of responding cells, but the average [Ca2+]i increase in 1 min was
      significantly reduced. The results indicate that P2Y2 receptors are present in
      rat mesangial cells but it cannot be excluded that there are receptors distinct
      from P2Y2 which also mediate a rise in [Ca2+]i.

PMID- 10204689
TI  - Specific changes in beta2-adrenoceptor trafficking kinetics and intracellular
      sorting during downregulation.
AB  - Agonist-activated beta2-adrenoceptors rapidly internalize and then recycle to the
      cell surface, however chronic agonist eventually causes receptor downregulation.
      To characterize beta2-adrenoceptor trafficking kinetics and intracellular sorting
      during downregulation, human embryonic kidney cells expressing epitope-tagged
      receptors were examined by radioligand binding with (+/-)-[3H]4-(3
      tertiarybutylamino-2-hydroxypropoxy)-benzimidazole- 2-on hydrochloride
      ([3H]CGP12177) and immunofluorescence microscopy. The first-order receptor
      recycling rate constant declined after 18 h of agonist compared with 15 min (0.05
      min(-1) vs. 0.12 min(-1)), thus increasing the intracellular transit time (20.0
      min vs. 8.3 min). There was also a reduction in the rate of receptor endocytosis
      and a decline in the total number of receptors. Although the intracellular
      receptor fraction did not increase between 15 min and 18 h of agonist, some
      receptors moved irreversibly into a protease-containing compartment while
      retaining radioligand binding activity. Our results indicate that beta2
      adrenoceptor downregulation is associated principally with an increased
      intracellular transit time during recycling. This could promote the diversion of
      receptors into protease-containing compartments, where there is an irreversible
      commitment to downregulation prior to loss of radioligand binding activity.

PMID- 10204690
TI  - Identification of a domain affecting agonist potency of meta
      chlorophenylbiguanide in 5-HT3 receptors.
AB  - The pharmacological properties of rat and human 5-HT3 receptors expressed in
      Xenopus oocytes were assessed using a two-electrode voltage clamp technique. Meta
      chlorophenylbiguanide (mCPBG), a 5-HT3 receptor-selective agonist, elicited
      typical current responses in both rat and human 5-HT3 receptor-expressing
      oocytes. However, the EC50 value for rat 5-HT3 receptors was 13-fold lower than
      for human 5-HT3 receptors. Using several chimeric human-rat 5-HT3 receptors, we
      identified a potential domain responsible for this difference in mCPBG-response.
      The domain is in the N-terminal extracellular region adjacent to the first
      transmembrane domain of rat 5-HT3 receptors and includes a rat-specific seven
      amino acid sequence (Phe197, Thr198, Lys199, Gln201, Ile205, Thr207 and Ser210).
      Replacement of corresponding amino acids in human 5-HT3 receptors by rat receptor
      residues increased the potency of mCPBG on human receptors indicating these amino
      acids play an important role in the pharmacological response to mCPBG.

PMID- 10204692
TI  - Detection of avian leukosis virus in albumen of chicken eggs using reverse
      transcription polymerase chain reaction.
AB  - A reverse transcriptase polymerase chain (RT-PCR) assay was developed to detect
      avian leukosis retrovirus (ALV) in egg albumen. Eggs of Single Comb White
      Leghorns were from a commercial breeder (stock F) and from a pathogen-free flock
      (stock N). RT-PCR was undertaken on isolated RNA from 20 unfertilized egg samples
      using seven sets of primers that correspond to the ALV gp85 envelope glycoprotein
      which determines the ALV subgroup classification. An ELISA assay for ALV gs
      antigen of egg albumen was positive for all stock F birds tested and negative for
      all stock N birds. Virus isolation was undertaken by inoculating egg albumen,
      feather pulp, or blood from five stock F chickens onto cultures of chicken embryo
      fibroblasts (C/E). IFA analysis of the inoculated C/E cultures indicated that all
      stock F birds tested contained infectious ALV. For the virus-positive stock F
      chickens, RT-PCR analyses using primers designed to detect all ALV subgroups
      detected ALV in 15/15 (100%) egg albumen samples, while primers designed to
      detect subgroup A ALV were positive for 12/15 (80%) egg albumen samples. RT-PCR
      products were not detected from five egg albumen samples from five stock N
      chickens by any primer sets. Direct sequencing using primers specific for
      subgroup A ALV verified the viral subgroup in the RT-PCR amplification products.
      The combined use of RT-PCR and direct sequencing of the RT-PCR product provides a
      new approach for identifying ALV-infected poultry.

PMID- 10204691
TI  - Comparison of the effects of dopamine D1 and D2 receptor antagonists on nerve
      growth factor mRNA expression.
AB  - Regulation of the expression of the nerve growth factor (NGF) gene has been
      reported previously to be mediated by the interaction of c-fos with an activator
      protein-1 (AP-1) binding site present in the first intron on the NGF gene. Using
      an RNase protection assay and in situ hybridization, we examined the effects of
      dopamine D1 and D2 receptor antagonists on NGF mRNA. Haloperidol (0.1-8 mg/kg)
      and (-)-sulpiride (10-100 mg/kg), induced NGF mRNA in a dose-dependent fashion in
      the hippocampus, piriform cortex, striatum and nucleus accumbens. The haloperidol
      (1 mg/kg)- and (-)-sulpiride (20 mg/kg)-induced NGF mRNA expression attained a
      maximum level 120 min after injection and returned to control levels 24 h later.
      Prior administration of the protein synthesis inhibitor cycloheximide blocked the
      haloperidol- and (-)-sulpiride-mediated induction of NGF mRNA. In contrast, R-(-)
      8-chloro-2,3,4,5-tetrahydro-3,1-methyl-5-phenyl-11-3-benzyoepin e-7-ol (SCH23390)
      did not induce NGF mRNA expression in either a dose-dependent or time-dependent
      manner. Our previous studies have shown that haloperidol and (-)-sulpiride induce
      the expression of c-fos and c-jun mRNAs and increase their AP-1 DNA binding
      activities. Thus, the data suggest that neuroleptics induce NGF gene expression
      by increasing AP-1 DNA binding activity.

PMID- 10204693
TI  - Enhanced binding to origin DNA at low pH enables easy detection of polyomavirus
      large T antigen by gel mobility shift assay of unfixed complexes.
AB  - Enhanced, stable binding by polyomavirus large T antigen to the viral DNA
      replication origin at pH 6 allowed the development of a gel mobility shift assay
      for the detection of large T antigen. Such assays were not possible at pH 7.6
      without previous fixation, due to instability of the complexes. We demonstrated
      that the gel mobility shift assay at pH 6 is very sensitive, allowing the
      detection of as little as 5 ng large T antigen, and is highly specific for DNA
      containing G(A/G)GGC target sequences. This method was used to detect large T
      antigen in crude cell lysates from transformed yeast cell lines or nuclear
      extracts from infected insect cells. Large T antigen-DNA complexes remained at or
      near the loading well in 5% acrylamide or 1.5% agarose gels, indicating that
      these complexes are very large. Glycerol gradient analysis showed that protein
      DNA complexes formed at pH 6 were massive, and that large T antigen also formed
      large complexes when incubated at low pH in the absence of DNA. These results
      show that pH has a major effect on binding of large T antigen to its multiple
      target sites in the viral origin of DNA replication, presumably by affecting
      protein-protein interactions that are important for the stability of large T
      antigen-DNA complexes.

PMID- 10204694
TI  - An international collaborative study on the detection of an HIV-1 genotype B
      field isolate by nucleic acid amplification techniques.
AB  - An international collaborative study to assess inter-laboratory variation in the
      sensitivity of gene amplification assays for the detection of HIV-1 RNA sequences
      was conducted using a panel of eight duplicate dilutions of an HIV-1 genotype B
      clinical isolate and negative control samples. Twenty-five laboratories
      participated in the study and used a variety of in-house assays and commercial
      assay systems. With few exceptions, the assays were more sensitive than a p24
      antigen assay. Overall, the PCR-based Amplicor Monitor assay was the most
      sensitive and gave the highest mean copy number for any one sample. Some of the
      in-house assays gave results comparable with the Monitor assay whilst the NASBA
      and bDNA assays appeared to be less sensitive. As a result of this study, an HIV
      1 Working Reagent for the standardisation of nucleic acid amplification assays
      was developed and assessed in a subsequent study. Similar differences in
      sensitivity between the different assay systems was observed. The discrepancies
      in viral copy number obtained using the Working Reagent highlights the need for
      an International Standard against which all Working Reagents may be calibrated.

PMID- 10204695
TI  - Quantitative sense-specific determination of murine coronavirus RNA by reverse
      transcription polymerase chain reaction.
AB  - In many applications, it is useful to know the sense and amount of viral RNAs
      present in a sample. In theory, sense-specific measurement of viral RNAs may be
      achieved by reverse transcription polymerase chain reaction (RT-PCR) assays which
      utilize primers of defined polarity during the RT step. However, in practice, it
      has been shown that such assays are prone to artifacts, such as non-specific
      priming, which drastically diminish their reliability. Using murine coronavirus
      MHV-4 as a model, we describe and validate several modifications of the RT-PCR
      procedure which eliminate these artifacts. Key RT-PCR parameters which were
      optimized include the design of tagged primers, DNase treatment of in vitro
      transcribed RNA standards, specification of temperature differences between RT
      and PCR annealing steps, and use of competitive RNA templates for quantitative
      assays. The assays described may be used to determine the sense and abundance of
      any viral or host RNA of interest in complex biological specimens.

PMID- 10204696
TI  - Restriction fragment length polymorphism analysis for rapid gag subtype
      determination of human immunodeficiency virus type 1 in South Africa.
AB  - A rapid method for identification of human immunodeficiency virus Type 1 (HIV-1)
      gag subtypes was developed based on restriction fragment length polymorphism
      (RFLP) analysis of 400 or 650 bp long polymerase chain reaction (PCR) fragments
      encompassing the start of the p17 (400 bp) and part of the p24 (650bp) regions.
      The consensus sequences of subtypes A-D, the only subtypes identified in South
      Africa, were analyzed to detect restriction endonucleases which generate unique
      patterns for each subtype. Four restriction endonucleases were identified: AluI,
      AccI, SwaI and XmnI. Digestion of a 400 bp fragment with AluI allowed
      identification of subtype C. Samples not identified were then reamplified, and a
      650 bp fragment digested with AccI to identify subtype B, followed by SwaI and
      XmnI to distinguish between subtypes A and D. This strategy was applied to 87
      samples previously subtyped by either sequence analysis of the gag p17 region (n
      = 33); or heteroduplex mobility assay (HMA) based on the env gene (n = 75); or
      both (n = 21). Out of the 87 samples, RFLP identified two samples as subtype A,
      28 as subtype B, 56 as subtype C and one as a subtype D virus. No discrepancies
      were found between RFLP gag subtypes and gag sequence subtypes demonstrating the
      reliability of this method. There was also no discordance between gag RFLP
      subtypes and env HMA subtypes, suggesting that there were no recombinant viruses
      detected relating to the genomic regions analyzed. RFLP is an effective technique
      for the rapid screening in an HIV epidemic of limited diversity, such as in South
      Africa.

PMID- 10204697
TI  - Multicenter evaluation of a new rapid automated human immunodeficiency virus
      antigen detection assay.
AB  - Although human immunodeficiency virus (HIV) antigen assays are of limited value
      for monitoring antiretroviral therapy, they play an important role for
      confirmatory testing of fourth generation HIV screening enzyme immunoassay (EIA)
      reactive samples. In a multicenter study, a new automated rapid p24 antigen
      assay, Elecsys HIV Ag (Roche Diagnostics Boehringer Mannheim GmbH, Penzberg,
      Germany), was compared to FDA licensed tests (Abbott HIV-1 Ag monoclonal and
      Coulter HIV-1 p24 antigen assay). In the evaluation 27 seroconversion panels were
      included, sera from the acute phase of infection, single and follow-up samples
      from HIV antibody positive patients, dilution series of HIV antigen positive
      standards, sera and cell culture supernatants infected with different HIV-1
      subtypes (A-H, and O) HIV-2 and recombinant HIV-1 (gag/env) isolates. To
      challenge the specificity of the new assay, 2565 unselected blood donors, sera
      from pregnant women, dialysis and hospitalized patients and 407 potentially cross
      reactive samples were investigated. Acute HIV infection was detected in three to
      eight seroconversion panels earlier with Elecsys HIV Ag than with the alternative
      assays. Higher numbers of serum samples from HIV infected patients tested
      positive by Elecsys HIV Ag than with the comparative assays. All HIV-1 subtypes
      and HIV-2 isolates were recognized with Elecsys HIV Ag. Abbott HIV-1 Ag
      monoclonal and Coulter HIV-1 p24 antigen assay showed a variable sensitivity for
      the different HIV-1 subtypes. The specificity of Elecsys HIV Ag and Coulter HIV-1
      p24 antigen assay were 99.8 and 99.93%, respectively. All the eight sera that
      were false reactive by Elecsys HIV Ag were tested negative with the Elecsys HIV
      Ag Neutralization Test. In conclusion, Elecsys HIV Ag was more sensitive than the
      alternative assays and showed a high specificity in combination with the
      neutralization assay. The very short incubation time of 18 min and the fully
      automated procedure of Elecsys HIV Ag which permits direct testing from the
      primary patient blood collection tube, represent a major improvement for routine
      laboratory diagnosis in comparison to the alternative assays.

PMID- 10204698
TI  - Comparative study of techniques used to recover viruses from residual urban
      sludge.
AB  - Eight virus extraction techniques were compared on three types of residual urban
      sludge for simultaneous detection of infectious enteroviruses, somatic
      coliphages, F-specific RNA bacteriophages and Bacteroides fragilis
      bacteriophages. The highest virus counts were found in extracts obtained using
      three extraction techniques described by respectively using a 10% beef extract
      solution at pH 9 and sonication, using a 0.3 M NaCl/7% beef extract solution at
      pH 7.5 and freon, and finally using a 0.1 M borate buffer/3% beef extract
      solution at pH 9 and sonication.

PMID- 10204699
TI  - Expression and characterization of Sapporo-like human calicivirus capsid proteins
      in baculovirus.
AB  - Sapporo-like caliciviruses reveal typical calicivirus morphology and cause acute
      gastroenteritis. This study describes the expression in baculovirus of capsid
      proteins of two Sapporo-like calicivirus strains (Hou/86 and Hou/90). Eight
      different constructs of the capsid genes were compared for production of the
      proteins. Constructs containing short (9 or 19 nt) upstream sequences failed to
      produce capsid proteins but extension of the upstream sequence to 73 nt resulted
      in production of capsid proteins. Expressed capsid protein with the MEG tri
      peptide as the N-terminus self-formed virus-like particles (VLPs). Expressed
      protein with an upstream AUG failed to form VLPs. Addition of His-tag to the N
      terminus of capsid protein also blocked VLP formation. Of three Norwalk-Hou/90
      chimeric capsid gene constructs, one resulted in production of chimeric capsid
      and the protein did not form VLPs. Recombinant capsid proteins for each of Hou/86
      and Hou/90 were further characterized. The expressed capsid antigens of the two
      strains were antigenically distinct but shared a common epitope(s). Further study
      of these proteins should allow development of immunologic assays for diagnosis
      and should help to clarify the epidemiology of Sapporo-like caliciviruses in
      humans.

PMID- 10204700
TI  - Comparison of specific and random priming in the reverse transcriptase polymerase
      chain reaction for genotyping group A rotaviruses.
AB  - This study describes an approach to the molecular typing of rotaviruses which
      requires only a single RNA extraction and reverse transcription (RT) reaction
      using random primers. Random-primed RT provides complementary DNA (cDNA) which
      can be used not only for G- and P-typing polymerase chain reactions (PCR), but
      also for the detection of other RNA viruses which may act as enteric pathogens.
      It is a sensitive and specific method that can detect 10 virus particles/ml of
      10% faecal suspension provided the cDNA is amplified in a nested typing-PCR. Of
      121 specimens positive for rotavirus by EM and analysed using this method, only
      8% could not be G- or P-genotyped. The untyped samples were tested again
      performing the RT reaction with G- and P-specific primers, achieving a 5%
      increase in sensitivity. Comparing G-genotyping against G-serotyping, 92% were
      genotyped through random priming RT-PCR whereas only 64% were serotyped using G
      serotype specific monoclonal antibodies (MAbs).

PMID- 10204701
TI  - Rapid feline immunodeficiency virus provirus quantitation by polymerase chain
      reaction using the TaqMan fluorogenic real-time detection system.
AB  - An improved quantitative polymerase chain reaction (qPCR) method based on a
      combination of real-time detection and the 5'-3' nuclease activity of the Taq DNA
      polymerase was developed to quantify the provirus load of feline immunodeficiency
      virus (FIV), a lentivirus of veterinary importance and an animal model for AIDS
      research. Two fluorogenic probes were designed to detect FIV provirus in genomic
      DNA of peripheral lymphocytes and tissues infected with different FIV subtypes.
      The most sensitive assay can detect one copy of FIV provirus. The assay showed
      excellent precision within-run and between-runs. Comparison of the TaqMan system
      with a conventional seminested PCR assay revealed a comparable detection limit
      and good correlation. Furthermore the design of the two probes allowed the
      detection of various FIV isolates of clade A and B.

PMID- 10204702
TI  - Recovery of infectious classical swine fever virus (CSFV) from full-length
      genomic cDNA clones by a swine kidney cell line expressing bacteriophage T7 RNA
      polymerase.
AB  - A new method for the recovery of infectious classical swine fever virus (CSFV)
      from full-length genomic cDNA clones of the C-strain was developed. Classical
      reverse genetics is based on transfection of in vitro transcribed RNA to target
      cells to recover RNA viruses. However, the specific infectivity of such in vitro
      transcribed RNA in swine kidney cells is usually low. To improve reverse genetics
      for CSFV, a stable swine kidney cell line was established that expresses
      cytoplasmic bacteriophage T7 RNA polymerase (SK6.T7). A 200-fold increased virus
      titre was obtained from SK6.T7 cells transfected with linearized full-length cDNA
      compared to in vitro transcribed RNA, whereas transfection of circular full
      length cDNA resulted in 20-fold increased virus titres. Viruses generated on the
      SK6.T7 cells are indistinguishable from the viruses generated by the classical
      reverse genetic procedures. These results show the improved recovery of
      infectious CSFV directly from full-length cDNAs. Furthermore, the reverse genetic
      procedures are simplified to a faster, one step protocol. We conclude that the
      SK6.T7 cell line will be a valuable tool for recovering mutant CSFV and will
      contribute to future pestivirus research.

PMID- 10204703
TI  - HBV viral load within subpopulations of peripheral blood mononuclear cells in HBV
      infection using limiting dilution PCR.
AB  - Extrahepatic viral load in peripheral blood mononuclear cells (PBMCs) of patients
      with hepatitis B virus (HBV) is still under debate. In this study, HBV infection
      rates and viral titers were examined within all PBMC subpopulations using
      limiting dilution-PCR (LD-PCR). PBMCs of patients with acute or chronic hepatitis
      B were separated by magnetic beads in monocytes, B-cells, CD4+ T-cells, CD8+ T
      cells, and NK cells. Using two-round nested PCR, HBV-DNA sequences were detected
      in all patients examined within each PBMC subpopulation. The frequencies of HBV
      positive cells and viral loads were calculated by Poisson analysis of HBV PCR
      results from serial dilutions of cells and cell lysates. Highest infection rates
      were found in monocytes and B-cells followed by CD8 + T-cells, NK cells, and CD4+
      T-cells. Concerning all subsets, frequencies of HBV-positive cells were 50- to
      500-fold higher in chronic than in acute hepatitis B. Viral loads were mostly
      estimated at about one HBV genome per HBV-positive cell. Moreover, slightly
      elevated HBV titers were seen in B-cells, CD4+ T-cells, and NK cells in both
      acute and chronic hepatitis B. It was demonstrated that beside a generally more
      latent HBV infection in PBMCs, elevated HBV titers point to replication or
      selective viral uptake within particular PBMC subsets. Therefore, the data
      suggest that HBV-infected PBMCs may participate in persistence of HBV.

PMID- 10204705
TI  - Identification of human cytomegalovirus variants by analysis of single strand
      conformation polymorphism and DNA sequencing of the envelope glycoprotein B gene
      region-distribution frequency in liver transplant recipients.
AB  - Single strand conformation polymorphism analysis (SSCP) of PCR-amplified DNA and
      subsequent DNA sequencing of human cytomegalovirus (HCMV) glycoprotein B (gB)
      gene were applied to identify known HCMV strains and to detect new virus
      variants. 61 HCMV PCR positive patients were studied out of a cohort of 410
      patients after liver transplantation (LTX). SSCP was able to distinguish between
      strains Davis, AD169, and Towne, and in addition could identify five new virus
      variants (Berlin B, C, E, F, and H). Their frequency, gB and gH types were
      determined. Simultaneous infections with two or three strains or variants, as
      well as a switch from one virus to another virus were observed during long-term
      follow-up. No correlation between the occurrence of certain virus strains or gB
      types and defined clinical manifestations of HCMV infection after LTX was drawn.

PMID- 10204704
TI  - Effect of potentially interfering substances on the measurement of HIV-1 viral
      load by the bDNA assay.
AB  - As high heterogeneity of plasma composition may be responsible for interference
      with HIV-1 viral load determination by the bDNA assay, the potential interference
      caused by a number of plasma components was examined. Among the biochemical
      substances assayed, cholesterol, bilirubin, and triglycerides did not affect
      viral load quantification. Hemoglobin did not interfere with the assay at
      concentrations lower than or equal to 14 g/dl. Above this concentration,
      measurements decreased by up to 0.78 log, but these hemoglobin levels do not
      usually occur in the clinical setting. None of the antiretroviral drugs assayed
      (AZT, dDC, d4T, 3TC and Indinavir) interfered with the measurement. HIV bDNA is a
      robust assay even in those frequent circumstances in which plasma composition
      differs notably from normal.

PMID- 10204706
TI  - Influenza virus serology--a comparative study.
AB  - Virus isolation or influenza virus antigen detection are the most rapid tests for
      diagnosis in the acute stage of influenza virus infection. As serology is easier
      to carry out, the synthesis of serum IgM, IgA and IgG was studied in two well
      defined patient groups, infected with influenza B virus (cohort 1, n = 37) and
      influenza A virus (cohort 2, n = 40), diagnosed by antigen detection and/or virus
      isolation within 36 h after onset of symptoms. IgM was found in 13 influenza B
      patients (35%), IgA in 12 patients (32%), whereas a significant antibody rise was
      found in 33 patients (92%) by enzyme-linked immunosorbent assay (ELISA) and 74%
      by haemagglutination inhibition assay (HAI). For the influenza A cohort these
      numbers were respectively 18 (45%), 27 (68%) and 24 (62%) HAI (72%). In age
      matched controls, who were bled on the first day of illness of the enrolled
      patient low prevalence was found for IgA and IgG, for influenza B respectively in
      2 and 18%, and for influenza A in 4 and 39%. Studying the kinetics of the
      antibody response, we found that virus specific IgA and the bulk of IgG is
      synthesised within the first week of the infection. It is concluded that the
      finding of a specific serum IgA is highly indicative of an acute influenza
      infection.

PMID- 10204707
TI  - Human anti-JC virus serum reacts with native but not denatured JC virus major
      capsid protein VP1.
AB  - The immunoreactivity of human anti-JC virus (JCV) serum against the major capsid
      protein VP1 of JCV was analyzed by Western blot, dot blot, and hemagglutination
      inhibition (HAI) assays. JCV-positive human serum reacted with native but not
      denatured JCV major capsid protein VP1, as demonstrated by dot blot and Western
      blot. Rabbit antiserum raised against native JCV capsid had immunoreactivities
      similar to those of human anti-JCV serum. These results indicate that the
      antigenecity of native and denatured JCV VP1 is different. In addition, both JCV
      positive human serum and rabbit antiserum raised against native JCV capsid
      protein inhibited the hemagglutination activity of JCV capsid particles. In
      contrast, rabbit antiserum raised against denatured JCV VP1 did not inhibit
      hemagglutination. These findings reveal that denaturation may alter the antigenic
      epitopes of JCV VP1. Therefore, keeping the JCV capsid protein native appears to
      be essential for serological or other immunological analyses of the virus.

PMID- 10204708
TI  - Lipofectin increases the specific activity of cypovirus particles for cultured
      insect cells.
AB  - Cytoplasmic polyhedrosis viruses (CPV) are classified as 14 distinct species
      (electropherotypes) within the genus Cypovirus, family Reoviridae. Cypovirus
      research has been limited by a lack of appropriate cell culture systems (for each
      of these virus species) in which the majority of cells can become productively
      infected. Lipofection increased the infection rate of Lymantria dispar 652 cells,
      by virus particles (derived from polyhedra) of Orgyia pseudosugata type 5
      cypovirus (Op-5 CPV), from 3 to 44%. Lipofection also significantly increased the
      percentage of Trichoplusia ni 368 cells infected with the same virus (from < 1 to
      approximately 7%). The spread of cypovirus infection between cells was either
      very slow or insignificant, and infected cells appeared to remain viable for long
      periods. Virus infection was detected by the observation of polyhedra formation
      in individual cells and it was therefore possible to develop a simple
      quantitative assay system to measure virus titre (TCID50). Cryo-electron
      microscopy showed that cypovirus particles formed a complex with the lipid,
      involving their envelopment within the liposome membrane. It was concluded that
      the increased infectivity of the virus by lipofection was due to a more efficient
      cell entry mechanism, probably involving fusion between liposome and cell
      membranes.

PMID- 10204709
TI  - Detection of porcine parvovirus DNA by the polymerase chain reaction assay using
      primers to the highly conserved nonstructural protein gene, NS-1.
AB  - Porcine parvovirus (PPV) infection is associated with reproductive losses in
      swine and its causative agent, the PPV, has been isolated worldwide. Serological
      surveys and virus isolation studies throughout Brazil confirm the occurrence of
      PPV infection in this country. The most common methods to detect PPV infection
      are fluorescent antibody staining of fetal tissues, hemagglutination assay of
      tissue extracts and virus isolation from fetal tissues. Non-specificity and low
      sensitivity are the major drawbacks of these techniques. The development of a
      polymerase chain reaction (PCR) and nested-PCR assays for PPV DNA detection from
      infected cell lines and clinical samples is described. The primers were designed
      to a highly conserved region of the PPV genome which codes for the non-structural
      protein, NS-1. Results showed that PCR could detect PPV in titres at least 10(6)
      higher than the hemagglutination assay. The PCR and nested-PCR assays were used
      to detect successfully PPV DNA in clinical samples.

PMID- 10204710
TI  - Detection of bovine retrospumavirus by the polymerase chain reaction.
AB  - A polymerase chain reaction (PCR) assay was developed for detection of bovine
      retrospumavirus (bovine syncytial virus; BSV) provirus DNA. Two different sets of
      oligonucleotide primers complementary to sequences located in the gag and the
      pol/env gene regions were used and compared for their ability to amplify the
      targeted BSV sequences by PCR. The results obtained from this study have shown
      that it is possible to amplify the BSV provirus DNA sequences not only from total
      DNA of BSV-infected cell cultures, but also from total DNA of various tissues and
      peripheral blood mononuclear cells (PBMCs) that were collected from two rabbits
      experimentally infected with BSV. Sensitivities of the PCR for amplification of
      BSV gag and pol/env nucleic acid sequences from cell culture total DNA were 10 ng
      and 10 pg of DNA, respectively, as determined by the analysis of the amplified
      PCR products on ethidium bromide-stained agarose gels. The specificity of the PCR
      for both primer sets tested was confirmed when the amplified cDNA products of the
      expected size reacted positively with the corresponding virus-specific
      digoxigenin-labeled cDNA probes in Southern blot chemiluminescent hybridization
      assays. No amplification was obtained when the BSV-specific primers were used in
      the PCR with DNA material specific to either bovine leukemia virus (BLV) or
      bovine immunodeficiency virus (BIV) provirus genomic DNA. No cross-hybridization
      was obtained when the BSV-specific cDNA probes were allowed to react with BLV or
      BIV provirus DNA. The PCR targeting the gag and pol/env gene regions of the BSV
      provirus genome may be an alternative to conventional methods for the
      confirmation of the presence of BSV in cell cultures used for virus isolation,
      and for the diagnosis of BSV infection from bovine peripheral blood leukocytes.

PMID- 10204711
TI  - A simplified and standardized neutralization enzyme immunoassay for the
      quantification of measles neutralizing antibody.
AB  - A simplified and standardized neutralization enzyme immunoassay (Nt-EIA) was
      developed to detect measles virus growth in Vero cells and to quantify measles
      neutralizing antibody. Heat-inactivated sera were diluted serially 4-fold and
      tested in duplicate. The 50% reduction point (50%RP) of virus growth was
      calculated using the Reed-Muench formula and the neutralizing antibody titre of
      test sera was converted into mIU/ml by comparing their 50%RP with that of the
      international standard serum. The optimal virus input and incubation time were
      found to be 50-100 plaque forming unit (PFU)/well and 64-72 h, respectively. The
      simplified Nt-EIA had a good reproducibility with only 3.7-4.2% of duplicate
      tests having a ratio > 4 in an evaluation of intra assay variation and the
      coefficients of variance were 2-9% in an evaluation of inter assay variation. In
      addition, the simplified Nt-EIA had a high sensitivity(98.6%), specificity (100%)
      and agreement (98.8%) in qualitative comparison with plaque reduction
      neutralization test (PRNT). In quantitative comparison, the correlation
      coefficient between Nt-EIA and PRNT was 0.83 without log transformation or 0.77
      after log transformation and 90% of 61 positive sera had a ratio < 4 between
      antibody titre tested by the two methods. The simplified Nt-EIA is thus a
      suitable alternative to the PRNT for the quantification of measles neutralizing
      antibody.

PMID- 10204712
TI  - Systematic review and meta-analysis of randomized controlled trials of cognitive
      behaviour therapy and behaviour therapy for chronic pain in adults, excluding
      headache.
AB  - A computer and a hand search of the literature recovered 33 papers from which 25
      trials suitable for meta-analysis were identified. We compared the effectiveness
      of cognitive-behavioural treatments with the waiting list control and alternative
      treatment control conditions. There was a great diversity of measurements which
      we grouped into domains representing major facets of pain. Effect sizes,
      corrected for measurement unreliability, were estimated for each domain. When
      compared with the waiting list control conditions cognitive-behavioural
      treatments were associated with significant effect sizes on all domains of
      measurement (median effect size across domains = 0.5). Comparison with
      alternative active treatments revealed that cognitive-behavioural treatments
      produced significantly greater changes for the domains of pain experience,
      cognitive coping and appraisal (positive coping measures), and reduced
      behavioural expression of pain. Differences on the following domains were not
      significant; mood/affect (depression and other, non-depression, measures),
      cognitive coping and appraisal (negative, e.g. catastrophization), and social
      role functioning. We conclude that active psychological treatments based on the
      principle of cognitive behavioural therapy are effective. We discuss the results
      with reference to the complexity and quality of the trials.

PMID- 10204713
TI  - Myofascial TMD does not run in families.
AB  - This study tests whether facial pain or associated symptoms and disorders
      aggregates in first degree relatives of those with myofascial temporomandibular
      disorders (M/TMD). We randomly selected one first degree relative of 106 probands
      with a lifetime history of M/TMD and one first degree relative of 118
      acquaintance control probands with no history of M/TMD. Relatives were directly
      interviewed about the lifetime occurrence of a broad range of painful and non
      painful health conditions and symptoms. Analyses revealed that rates of facial
      pain, symptoms of TMDs, and a range of other musculoskeletal conditions were not
      significantly different in first degree relatives of M/TMD probands and first
      degree relatives of controls. In addition, proband descriptors of facial pain
      severity or disability did not significantly predict the likelihood of having a
      first degree relative with one or more TMD-related symptoms. These results
      indicate that M/TMD is not a familial disorder.

PMID- 10204714
TI  - Anesthesia-based pain services improve the quality of postoperative pain
      management.
AB  - Anesthesia-based pain services are facilitating improvements in the quality of
      care of surgical patients by developing and directing institution-wide
      perioperative analgesia programs that include interdisciplinary collaborations.
      However, the impact of anesthesia-based pain services has not been evaluated in a
      systematic fashion. This prospective multisite study (n = 23 hospitals) utilized
      a standardized approach to evaluate the quality of pain care provided to patients
      who were and who were not cared for by an anesthesia-based pain service. A total
      of 5837 patients were evaluated using a standardized survey that consisted of a
      medical record review and a patient interview. The data were collected as part of
      the hospitals' quality improvement activities. Forty-nine percent of the patients
      were cared for by an anesthesia-based pain service. Patients who received pain
      service care reported significantly lower pain intensity scores; had lower levels
      of pain in the postoperative period; had a lower incidence of pruritus, sedation,
      and nausea; and experienced significantly less pain than expected. In addition,
      these patients were more likely to receive patient education about postoperative
      pain management; were more satisfied with their postoperative pain management;
      and were discharged sooner from the hospital. The findings from this study
      demonstrate that the care provided by anesthesia-based pain services has a
      significant impact on patient outcomes.

PMID- 10204715
TI  - Exogenous and endogenous adenosine enhance the spinal antiallodynic effects of
      morphine in a rat model of neuropathic pain.
AB  - Adenosine analogs produce antinociception in normal animals and reduce allodynia
      and hyperalgesia following inflammation and nerve injury following spinal
      injection, yet none have been tested for clinical safety. While adenosine itself
      is in clinical trials for spinal administration, there is little data on the
      spinal effects of adenosine in animal models. In this study, we determined that
      the spinal administration of adenosine produced a dose-dependent reduction in
      tactile allodynia in rats following spinal nerve ligation without producing motor
      blockade. Although the maximal effect of adenosine was less than 50% reversal of
      allodynia, its duration of action was >24 h after a single spinal injection. In
      contrast, injection of a synthetic adenosine analog which produced an anti
      allodynic action to a similar degree of effect resulted in a pronounced motor
      blockade. Spinal opioid action has been suggested to result in part from spinal
      adenosine release. We hypothesized that the reduced efficacy of spinal morphine
      in nerve injury-induced allodynia and hyperalgesia might reflect a disruption in
      this spinal opioid-adenosine mechanism. Spinal morphine itself produced a minimal
      reduction in allodynia in rats following spinal nerve ligation and this was
      enhanced in an additive manner by spinal adenosine. The maximal effect of this
      combination resulted in less than 60% reversal of allodynia. In contrast, spinal
      injection of adenosine deaminase or reuptake inhibitors greatly enhanced the
      effect of spinal morphine, resulting in over 80% reversal of allodynia. These
      results support the clinical testing of spinal adenosine alone and with morphine
      in the treatment of neuropathic pain, and further testing of the proposed opioid
      adenosine link in normal and hyperesthetic conditions.

PMID- 10204716
TI  - Redox manipulation of NMDA receptors in vivo: alteration of acute pain
      transmission and dynorphin-induced allodynia.
AB  - The redox modulatory site of the N-methyl-D-aspartate (NMDA) receptor directly
      regulates NMDA receptor function. Sulfhydryl reducing agents, such as
      dithiothreitol (DTT), potentiate NMDA receptor-evoked currents in vitro, whereas
      oxidizing agents, such as 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB), attenuate
      these currents. In this study, we examined the effect of this redox manipulations
      on nociceptive spinal cord signaling in mice. Intrathecal (i.t.) administration
      of DTT (0.1-30 nmol), presumably reducing the NMDA receptor, dose-dependently
      enhanced NMDA-induced nociceptive behaviors, and this enhancement was blocked by
      the oxidizing agent, DTNB. Pretreatment with DTT (10 nmol, i.t.) enhanced NMDA
      induced tail-flick thermal hyperalgesia and intraplantar formalin-induced
      nociceptive behaviors. Finally, DTT pretreatment enhanced the long lasting
      allodynia induced by i.t. administration of dynorphin, whereas post-treatment
      with DTNB reduced the permanent allodynia induced by dynorphin for 5 days.
      Potentiation of all four of these NMDA-dependent nociceptive behaviors by DTT
      suggests that the reduction of the NMDA receptor by endogenous reducing agents
      may contribute to augmented pain transmission in response to activation by
      endogenous glutamate. Moreover, blockade of in vivo NMDA receptor reducing agents
      or oxidation of the NMDA receptor redox site may prove therapeutically useful in
      the treatment of chronic pain.

PMID- 10204717
TI  - Peripheral antinociceptive action of amitriptyline in the rat formalin test:
      involvement of adenosine.
AB  - The present study determined (1) whether amitriptyline could produce a local
      antinociceptive action in the formalin test, (2) whether endogenous adenosine was
      involved in this action, and (3) which other systems might contribute to such an
      action. Coadministration of amitriptyline 10-100 nmol with 2.5% formalin produced
      a dose-related reduction in phase 1 (0-12 min) and phase 2 (16-60 min) flinching
      behaviours, as well as in phase 2 biting/licking time (no phase 1 expression).
      This action was not seen or only partially expressed at low concentrations of
      formalin (0.5%, 0.75%). Coadministration of caffeine with amitriptyline partially
      reversed the antinociceptive action of amitriptyline against both behaviours at
      2.5% formalin. At 1.5% formalin, caffeine still produced only a partial reversal
      of effect; this appeared to be due to a block of adenosine A1 receptors, as it
      was also seen with the selective adenosine A1 receptor antagonist, 8-cyclopentyl
      1,3-dimethylxanthine. Using antagonists for a number of other systems, no
      evidence for an involvement of alpha-adrenergic, histamine, excitatory amino acid
      or opioid receptors in the action of amitriptyline was observed or inferred. A
      local anaesthetic action for amitriptyline remains a possibility for the residual
      action. These results indicate that amitriptyline can produce a local peripheral
      antinociceptive action which is mediated, in part, by an interaction with
      endogenous adenosine, most likely an inhibition of the cellular uptake of
      adenosine with a consequent activation of adenosine A1 receptors on sensory nerve
      terminals. Local application of amitriptyline by cream or gel might prove to be a
      useful method of drug delivery in inflammatory pain states.

PMID- 10204718
TI  - Differential effects of neurotoxic destruction of descending noradrenergic
      pathways on acute and persistent nociceptive processing.
AB  - Although many pharmacological studies indicate that bulbospinal noradrenergic
      projections contribute to antinociception, lesions of the major brainstem
      noradrenergic cell groups have provided conflicting evidence. Here we used a new
      immunotoxin, anti-dopamine beta-hydroxylase-saporin, to re-examine the
      contribution of noradrenergic pathways to nociception and to morphine analgesia.
      We treated rats intrathecally by lumbar puncture with the immunotoxin and
      examined dopamine beta-hydroxylase (DbetaH) immunoreactivity seven and 14 days
      after treatment. There was no change in DbetaH staining at 7 days; however, 14
      days after treatment we demonstrated significant destruction of noradrenergic
      neurons in the locus coeruleus and in the A5 and A7 cell groups. There was a
      concomitant loss of noradrenergic axons in the dorsal and ventral horns of the
      lumbosacral and cervical cord. Consistent with the lack of anatomical changes, we
      found no difference in nociceptive responses in the hot-plate, tail-flick or
      formalin tests one week post-toxin. On day 14 we examined the behavioral response
      to injection of formalin into the hindpaw and found that responses during the
      second phase of pain behavior were significantly reduced. There was no change
      during the first phase. Formalin-evoked fos expression in the spinal cord was
      also reduced. We also evaluated morphine analgesia in the formalin test and found
      that toxin-treated animals exhibited enhanced morphine analgesia. These results
      establish the utility of using this immunotoxin to selectively destroy
      subpopulations of noradrenergic cell groups and provide evidence that acute and
      persistent nociception are differentially regulated by descending noradrenergic
      pathways.

PMID- 10204719
TI  - Heritability of nociception I: responses of 11 inbred mouse strains on 12
      measures of nociception.
AB  - It is generally acknowledged that humans display highly variable sensitivity to
      pain, including variable responses to identical injuries or pathologies. The
      possible contribution of genetic factors has, however, been largely overlooked.
      An emerging rodent literature documents the importance of genotype in mediating
      basal nociceptive sensitivity, in establishing a predisposition to neuropathic
      pain following neural injury, and in determining sensitivity to pharmacological
      agents and endogenous antinociception. One clear finding from these studies is
      that the effect of genotype is at least partially specific to the nociceptive
      assay being considered. In this report we begin to systematically describe and
      characterize genetic variability of nociception in a mammalian species, Mus
      musculus. We tested 11 readily-available inbred mouse strains (129/J, A/J, AKR/J,
      BALB/cJ, C3H/HeJ, C57BL/6J, C58/J, CBA/J, DBA/2J, RIIIS/J and SM/J) using 12
      common measures of nociception. These included assays for thermal nociception
      (hot plate, Hargreaves' test, tail withdrawal), mechanical nociception (von Frey
      filaments), chemical nociception (abdominal constriction, carrageenan, formalin),
      and neuropathic pain (autotomy, Chung model peripheral nerve injury). We
      demonstrate the existence of clear strain differences in each assay, with 1.2 to
      54-fold ranges of sensitivity. All nociceptive assays display moderate-to-high
      heritability (h2 = 0.30-0.76) and mediation by a limited number of apparent
      genetic loci. Data comparing inbred strains have considerable utility as a tool
      for understanding the genetics of nociception, and a particular relevance to
      transgenic studies.

PMID- 10204720
TI  - Heritability of nociception II. 'Types' of nociception revealed by genetic
      correlation analysis.
AB  - Clinical pain syndromes, and experimental assays of nociception, are
      differentially affected by manipulations such as drug administration and exposure
      to environmental stress. This suggests that there are different 'types' of pain.
      We exploited genetic differences among inbred strains of mice in an attempt to
      define these primary 'types'; that is, to identify the fundamental parameters of
      pain processing. Eleven randomly-chosen inbred mouse strains were tested for
      their basal sensitivity on 12 common measures of nociception. These measures
      provided for a range of different nociceptive dimensions including noxious
      stimulus modality, location, duration and etiology, among others. Since
      individual members of inbred strains are identical at all genetic loci, the
      observation of correlated strain means in any given pair of nociceptive assays is
      an index of genetic correlation between these assays, and hence an indication of
      common physiological mediation. Obtained correlation matrices were subjected to
      multivariate analyses to identify constellations of nociceptive assays with
      common genetic mediation. This analysis revealed three major clusters of
      nociception: (1) baseline thermal nociception, (2) spontaneously-emitted
      responses to chemical stimuli, and (3) baseline mechanical sensitivity and
      cutaneous hypersensitivity. Many other nociceptive parameters that might a priori
      have been considered closely related proved to be genetically divergent.

PMID- 10204721
TI  - Hemisensory impairment in patients with complex regional pain syndrome.
AB  - The purpose of the present study was to investigate the extent and quality of
      sensory impairment and their relation to pain characteristics and movement
      disorders in patients suffering from complex regional pain syndrome (CRPS) type
      I. Neurological testing was performed independently by two examiners in 24
      patients with CRPS type I. In eight patients (33%), a hemisensory impairment with
      decreased temperature and pinprick sensation ipsilateral to the limb affected by
      CRPS could be observed. In four patients (17%), a sensory deficit in the upper
      quadrant of the body could be demonstrated and in eight patients (33%), sensory
      impairment was limited to the limb affected by CRPS. Mechanical allodynia and
      mechanical hyperalgesia could be observed in a higher percentage of patients with
      hemisensory deficit or sensory impairment in the upper quadrant (92%), than in
      those patients with sensory impairment limited to the affected limb (17%) (P <
      0.005). In patients with left-sided CRPS, sensory abnormalities in the upper
      quadrant or hemisensory impairment were more frequently demonstrated (77%) than
      in patients with right-sided CRPS (18%) (P < 0.005). There was a high correlation
      (92%) for the sensory findings between the two examiners, and hemisensory
      abnormalities were stable over a period of 3-6 months in all six patients with
      repeated examinations. Motor impairment (contractures, weakness, tremor or
      difficulties in initiating movement) could be observed in a higher percentage in
      patients with sensory abnormalities in the upper quadrant or hemisensory
      impairment (83%) than in patients with sensory impairment limited to the affected
      limb (42%) (P < 0.05) and was significantly correlated with
      allodynia/hyperalgesia (P < 0.005). The results demonstrated that sensory
      deficits in patients with CRPS, frequently extend past the painful area of the
      affected limb. The increased frequency of mechanical allodynia and movement
      disorders in patients with hemisensory impairment or sensory deficits in the
      upper quadrant, might indicate that central mechanisms are involved in the
      pathogenesis of CRPS in these patients.

PMID- 10204722
TI  - Differential inhibitory effect on human nociceptive skin senses induced by local
      stimulation of thin cutaneous fibers.
AB  - It is known that stimulation of thin cutaneous nerve fibers can induce long
      lasting analgesia through both supraspinal and segmental mechanisms, the latter
      often exhibiting restricted receptive fields. On this basis, we recently
      developed a new method, termed cutaneous field stimulation (CFS), for localized
      stimulation of A delta and C fibers in the superficial part of the skin. In the
      present study, we have evaluated the effects of CFS on non-nociceptive and
      nociceptive skin senses. We compared the effects of CFS with those of
      conventional transcutaneous electrical nerve stimulation (TENS), known to
      preferentially activate coarse myelinated fibers. A battery of sensory tests were
      made on the right volar forearm of 20 healthy subjects. CFS (16 electrodes, 4 Hz
      per electrode, 1 ms, up to 0.8 mA) and TENS (100 Hz, 0.2 ms, up to 26 mA) applied
      either on the right volar forearm (homotopically), or on the lower right leg
      (heterotopically) were used as conditioning stimulation for 25 min. The tactile
      threshold was not affected by either homo- or heterotopical CFS or TENS. The mean
      thresholds for detecting warming or cooling of the skin were increased by 0.4-0.9
      degrees C after homo- but not heterotopical CFS and TENS. Regarding nociceptive
      skin senses, homo- but not heterotopical CFS, markedly reduced CO2-laser evoked A
      delta- and C fiber mediated heat pain to 75 and 48% of control, respectively, and
      mechanically evoked pain to 73% of control. Fabric evoked prickle, was not
      affected by CFS. Neither homo- nor heterotopical TENS induced any marked
      analgesic effects. It is concluded that different qualities of nociception can be
      differentially controlled by CFS.

PMID- 10204723
TI  - Predictors of early improvement in low back pain amongst consulters to general
      practice: the influence of pre-morbid and episode-related factors.
AB  - Low back pain symptoms are extremely common. affecting as many as 80% of the
      population at some time in their lives. However, the majority of the medical
      costs arise from the minority of patients whose symptoms become chronic. The
      authors propose a model in which chronicity is determined not only by factors
      related to the episode of low back pain, but also factors prior to the onset of
      symptoms (pre-morbid factors). No previous study has collected information on
      predictors of low back pain chronicity prior to the onset of symptoms.
      Participants in the South Manchester Low Back Pain Study, recruited by means of a
      cross-sectional population survey were followed prospectively over 18 months to
      identify those who consulted their general practitioner with a new episode of low
      back pain. At interview, 1-2 weeks post-consultation, it was determined whether
      or not subjects' symptoms had improved. In males, low levels of psychological
      distress, a higher than average reported level of physical activity, being in
      employment, and being satisfied with current work status were associated with a
      quick improvement in symptoms. In addition factors related to the episode, namely
      a short duration before consultation and symptoms with a sudden onset and
      confined to the lower back area, also strongly predicted a good early outcome.
      Using information on both pre-morbid and episode related factors, groups of male
      patients were identified whose probability of an early resolution of symptoms
      ranged between 0.25 and 1. Few factors, either pre-morbid or episode-related,
      were strongly associated with outcome amongst females. This large population
      based study has shown, despite the known heterogeneity in the origin of low back
      pain and the pathologies associated with symptoms, an early improvement in
      symptoms amongst male attenders at general practice can be predicted on the basis
      of a small number of variables.

PMID- 10204724
TI  - Potential uses of topical opioids in palliative care--report of 6 cases.
AB  - Opioids used topically may exercise several useful clinical effects. Opioids may
      cause immediate local analgesia and also may work indirectly through decreasing
      the inflammation process. In this article we describe six patients treated with
      topical opioids because of cutaneous pain due to tumor infiltration. skin ulcers
      of malignant and non-malignant origin, severe oral mucositis, pain due to knee
      arthrosis and severe tenesmoid pain. In all but one case, topical morphine
      provided rapid relief which lasted usually for 7-8 h. The side effects of topical
      opioids were none or minimal. Possible mechanisms of topical analgesia are
      discussed.

PMID- 10204726
TI  - Heel lancing in term new-born infants: an evaluation of pain by frequency domain
      analysis of heart rate variability.
AB  - The aim of the investigation was to assess pain by frequency domain analysis of
      heart rate variability (HRV) during a routine heel lancing procedure in term new
      born infants. Beat-to-beat heart rate (HR) was recorded in 23 healthy new-born
      infants on the maternity ward during blood sampling for neonatal screening. A
      sham heel prick prior to the sharp lancing procedure was performed randomly in
      half of the infants. Spectral analysis of HRV was assessed for each of the
      following sequences: (1) baseline (2) sham heel prick (3) sharp heel prick and
      (4) squeezing the heel for blood sampling. The response to the sham prick did not
      differ significantly from the sharp prick. Compared with the baseline, sharp
      lancing gave rise to minor increases in HR and variability in the low frequency
      band of the spectral analysis. A clear stress response was provoked when the heel
      was squeezed for blood sampling, indicated by an increased HR and a decreased
      spectral power in the high frequency band (i.e. lower vagal tone). The different
      stress responses during the lancing and the squeezing of the heel were clearly
      illustrated when principal component analysis was applied and the vectors for the
      changes in HR and spectral pattern were indicated. In conclusion, the squeezing
      of the heel is the most stressful event during the heel prick procedure.

PMID- 10204725
TI  - Nucleus reticularis gigantocellularis and nucleus raphe magnus in the brain stem
      exert opposite effects on behavioral hyperalgesia and spinal Fos protein
      expression after peripheral inflammation.
AB  - Previous findings indicate that the brain stem descending system becomes more
      active in modulating spinal nociceptive processes during the development of
      persistent pain. The present study further identified the supraspinal sites that
      mediate enhanced descending modulation of behavior hyperalgesia and dorsal horn
      hyperexcitability (as measured by Fos-like immunoreactivity) produced by
      subcutaneous complete Freund's adjuvant (CFA). Selective chemical lesions were
      produced in the nucleus raphe magnus (NRM), the nuclei reticularis
      gigantocellularis (NGC), or the locus coeruleus/subcoeruleus (LC/SC). Compared to
      vehicle-injected animals with injection of vehicle alone, microinjection of a
      serotoninergic neurotoxin 5,7-dihydroxytryptamine into the NRM significantly
      increased thermal hyperalgesia and Fos protein expression in lumbar spinal cord
      after hindpaw inflammation. In contrast, the selective bilateral destruction of
      the NGC with a soma-selective excitotoxic neurotoxin, ibotenic acid, led to an
      attenuation of hyperalgesia and a reduction of inflammation-induced spinal Fos
      expression. Furthermore, if the NGC lesion was extended to involve the NRM, the
      behavioral hyperalgesia and CFA-induced Fos expression were similar to that in
      vehicle-injected rats. Bilateral LC/SC lesions were produced by microinjections
      of a noradrenergic neurotoxin, DSP-4. There was a significant increase in
      inflammation-induced spinal Fos expression, especially in the ipsilateral
      superficial dorsal horn following LC/SC lesions. These results demonstrated that
      multiple specific brain stem sites are involved in descending modulation of
      inflammatory hyperalgesia. Both NRM and LC/SC descending pathways are major
      sources of enhanced inhibitory modulation in inflamed animals. The persistent
      hyperalgesia and neuronal hyperexcitability may be mediated in part by a
      descending pain facilitatory system involving NGC. Thus, the intensity of
      perceived pain and hyperalgesia is fine-tuned by descending pathways. The
      imbalance of these modulating systems may be one mechanism underlying variability
      in acute and chronic pain conditions.

PMID- 10204727
TI  - Assessment of peripheral sympathetic nervous function for diagnosing early post
      traumatic complex regional pain syndrome type I.
AB  - Clinical diagnosis of complex regional pain syndrome type I (CRPS I) in post
      traumatic patients is often delayed since the clinical appearance of this disease
      resembles normal post-traumatic states to a certain extent (pain, edema, loss of
      function). The purpose of this study was to assess the incidence of specific
      clinical features in CRPS I patients and normal post-traumatic patients and to
      evaluate the diagnostic value of a bedside test that measures the sympathetic
      nervous function. Fifty patients with post-traumatic CRPS I of the upper limb and
      50 patients 8 weeks after distal radius fracture with an undisturbed course of
      disease were subjected to a detailed clinical examination. Pain was assessed
      using the VAS (visual analog scale), skin temperature measured with an infrared
      camera and grip-strength with a pneumatic manometer. In CRPS I patients, motor
      disturbances defined as an impaired active range of motion of the hand, were most
      frequent (96%, fracture patients: 40%), followed by edema (88%, fracture
      patients: 80%) and spontaneous pain (VAS 4.0 +/- 2.3, fracture patients: VAS 1.3
      +/- 0.6). Systematic temperature differences (>1 degree C) between the affected
      and unaffected limbs were seen in only 42% of CRPS I patients and in 34% of the
      fracture patients. Further sensory, sudomotor or trophic changes of the hands
      were rare. As expected, there were significant differences in the quantity of
      edema, motor disturbances and sensory disturbances between CRPS I patients and
      normal fracture patients. However, normal fracture patients still suffered from
      several of the evaluated symptoms 8 weeks after trauma, which makes an early
      clinical diagnosis of the complication more difficult. Using a newly developed
      bedside test, the peripheral sympathetic nervous function was assessed in both
      groups of patients and in 50 age-matched healthy controls. The decrease in skin
      blood flow following sympathetic provocation maneuvers, detected by laser Doppler
      flowmetry, was quantified as sympathetic reactivity. In the affected hands of
      CRPS I patients, as well as in the contralateral hands, the sympathetic
      reactivity was obliterated or diminished in contrast to the age-matched controls
      and normal fracture patients. A multivariate analysis did not reveal any
      correlation between sympathetic function and the severity of any clinical
      symptom. Sympathetic reactivity seems to be an independent variable in CRPS I and
      the test presented may facilitate the difficult clinical diagnosis of this
      disease.

PMID- 10204728
TI  - Spinal nerve ligation-induced neuropathy in the rat: sensory disorders and
      correlation between histology of the peripheral nerves.
AB  - We studied the effect of unilateral ligation of two spinal nerves on behavioral
      pain responses evoked by various types of cutaneous stimuli in the adult rat.
      Furthermore, we determined the effect of spinal nerve ligation on morphology of
      the peripheral nerves. The most consistent behavioral finding (83%) was a marked
      decrease in monofilament-induced hindlimb withdrawal thresholds (mechanical
      allodynia) ipsilateral to the spinal nerve ligation. This mechanical allodynia
      was observed as early as during the 1st post-operative day and it persisted up to
      2 months (the maximum length of the observation period). In contrast,
      hyperalgesia to noxious mechanical stimulation (Randal-Sellitto test) was not
      observed in allodynic rats until the 3rd post-operative day. In a minority of
      rats (13%), spinal nerve ligation-induced mechanical hyperalgesia without a
      concomitant mechanical allodynia. There was no corresponding heat hyperalgesia in
      the injured hindlimb (hot water immersion-, radiant heat- or hot-plate-induced
      hindlimb withdrawal tests). In contrast, hypoalgesia to heat was observed on the
      1st postoperative day, but not later. Neuropathological analysis of the
      peripheral nerves revealed a dramatic decrease in the number of myelinated nerve
      fibers distal to the spinal nerve ligation site. The results support the previous
      evidence indicating that ligation of spinal nerves induces a marked allodynia to
      mechanical stimulation. However, this mechanical allodynia may differentially
      dissociate from mechanical and thermal hyperalgesia at various post-operative
      time points. The marked mechanical allodynia together with a dramatic decrease in
      the number of myelinated nerve fibers is paradoxical, since the activation of
      myelinated nerve fibers by monofilaments produced abnormally strong behavioral
      responses. This paradox may be explained by spinal nerve ligation-induced
      amplification or disinhibition of tactile signals at central levels.

PMID- 10204729
TI  - Patterns of hyperalgesia in complex regional pain syndrome.
AB  - Complex regional pain syndrome (CRPS) is characterized by a triad of sensory,
      motor and autonomic dysfunctions, with long-standing pain and temperature
      differences of the affected and contralateral limb as predominant symptoms. The
      pathogenesis of the disorder still remains unclear. Among the main hypotheses of
      an underlying pathophysiology we find inflammatory processes and dysfunction of
      the sympathetic nervous system. Whether the main site of dysfunction is found
      centrally or peripherally is not known. With psychophysical methods we studied
      patterns of hyperalgesia to obtain a better understanding of the neuropathic pain
      component in CRPS. Forty patients in an acute phase of CRPS and a median duration
      of the disease of 10 weeks, were included in the study. Hyperalgesia to heat was
      tested with a thermode providing feedback-controlled temperature increases. Two
      forms of mechanical hyperalgesia were examined: phasic mechanical stimuli by
      using a custom-made impact stimulator for the determination of individual pain
      thresholds, tonic mechanical stimuli were applied using a pinch-device.
      Additionally a 'wind-up' paradigm was used to study a pain phenomenon of presumed
      central origin: a defined impact stimulus was given once and five times in
      repetition. A subpopulation of patients was reevaluated for mechanical
      hyperalgesia after i.v. injection of 500 mg acetyl-salicylic acid. Hyperalgesia
      to heat was insignificant. We found, however, a marked mechanical hyperalgesia to
      phasic impact stimuli (P < 0.005), whereas, static stimulation (squeezing skin
      folds) results were insignificant again. Wind-up related pain was also
      significantly enhanced in the affected limb (P < 0.02). The anti-inflammatory
      agent had no effect. These results indicate a non-inflammatory pathogenesis in
      CRPS presumably central in origin.

PMID- 10204730
TI  - Unravelling age effects and sex differences in needle pain: ratings of sensory
      intensity and unpleasantness of venipuncture pain by children and their parents.
AB  - Age and sex differences were investigated in children's self-report of
      venipuncture pain. Equal numbers of boys and girls aged 3-15 years (n = 110) made
      separate ratings of the intensity and unpleasantness of their needle pain, using
      a paired Visual Analogue Scale (VAS) technique. The parents of these children
      used the same method to give ratings of predicted pain and unpleasantness before
      the needle, as well as ratings based on observing their child during the needle.
      Results showed that, across age, children's intensity and unpleasantness scores
      were highly correlated (r = 0.78), and that both of these ratings decreased with
      increasing age. Analyses of covariance showed that, with the variance in the
      unpleasantness ratings accounted for, a significant age main effect persisted for
      the intensity ratings (scores decreasing with increasing age), with no effect of
      sex. In the corollary analysis, with intensity scores entered as a covariate,
      unpleasantness ratings showed no main effect of age, but a significant main
      effect of sex emerged: girls' ratings of pain unpleasantness, when averaged
      across age, were significantly higher than boys'. The interaction between age and
      sex was explored in analysis of the relative difference between intensity and
      unpleasantness ratings. The results indicated that, from approximately 8-years of
      age, children (especially girls) gave significantly higher ratings of
      unpleasantness than sensory intensity of needle pain. Prior to the age of 8
      years, children tended to give equivalent ratings of intensity and
      unpleasantness, with no evidence of a sex difference. The agreement between
      parental and children's ratings was higher for parents' observed, as opposed to
      predicted, scores, especially for pain intensity, with no systematic influence of
      the child's age and sex. In conclusion, it is suggested that age effects in
      children's self-report of needle pain are predominantly manifest in ratings of
      sensory intensity, whilst sex effects are predominantly manifest in ratings of an
      affective (unpleasantness) dimension. It is argued that both age and sex
      differences are largely the function of pain reporting variables, rather than
      reflecting fundamental age or sex based variance in nociceptive processing.

PMID- 10204731
TI  - Electrophysiological testing of the trigeminofacial system: aid in the diagnosis
      of atypical facial pain.
AB  - The aim of this study was to evaluate the yield of objective electrophysiological
      testing of the trigeminofacial system in atypical facial pain (AFP). In addition
      to the clinical neurological examination, two brainstem reflexes covering both
      the peripheral parts and the central connections of the trigeminal and the facial
      nerves, the blink and jaw reflexes (BR and JR), were recorded in 17 AFP patients.
      The control group consisted of 18 healthy volunteers with no history of facial
      pain or chronic headache. The AFP patients could be divided into three distinct
      groups on the basis of the clinical and electrophysiological findings. (1) Major
      trigeminal neuropathy. Four patients had clinical and electrophysiological signs
      of trigeminal neuropathy (three patients with an afferent pattern of abnormal BR,
      and one with absent JR on the clinically affected side) despite normal findings
      in the MRI-scans of the brain. Thus, electrophysiological testing may be more
      sensitive than MRI in demonstrating pathology in some of the AFP patients. (2)
      Minor trigeminal neuropathy. Seven patients had signs of increased excitability
      of the BR in the form of uni- or bilaterally abnormal (diminished or absent)
      habituation of the R2 component of the BR; two of these patients also showed
      clinical signs of trigeminal dysfunction, but the MRI-scans were all normal. This
      deficient habituation of the BR indicates increased excitability of the BR at
      brainstem level in nearly 50% of our AFP patients. (3) 'Idiopathic', no signs of
      trigeminal neuropathy. Five patients had normal findings both in the brainstem
      reflex recordings and in the clinical examinations. Additionally, one patient had
      abnormal BAEP and EEG recordings. On the group level, the AFP patients had
      significantly higher thresholds of the tactile R1 component of the BR than the
      control subjects. Electrophysiological testing may offer a valuable tool for both
      the clinical evaluation, and the scientific study of AFP.

PMID- 10204732
TI  - Indirect costs of back pain in the Netherlands: a comparison of the human capital
      method with the friction cost method.
AB  - In this study we estimated the indirect costs of back pain in 1991 in The
      Netherlands on the basis of two approaches: the traditionally used human capital
      method and the more recently developed friction cost method. The indirect costs
      of illness were defined as the value of production losses of paid labour and
      related costs to society due to back pain. The results of this study in 1991 in
      The Netherlands show that the short-term indirect costs estimated by the human
      capital method were more than three times as high as the indirect costs estimated
      by the friction cost method (US$ 4.6 billion vs. USS 1.5 billion, respectively).
      The lower estimate of indirect costs when using the friction cost method is
      mainly due to the fact that in this method actual production losses are estimated
      during a relatively short friction period, which is defined as the period needed
      to restore the initial production level. In contrast with the human capital
      method, long-term absenteeism and disability do not induce additional costs when
      applying the friction cost method. Since the friction cost method takes into
      account that employees can be replaced, we believe that this method produces a
      more accurate estimate of indirect costs than the human capital method.
      Notwithstanding the resulting decrease in indirect costs of back pain, these
      costs are still impressive, representing 0.28% of the GNP in The Netherlands in
      1991. As a consequence, but particularly stimulated by structural changes in the
      Dutch social security system, policies aimed at reducing indirect costs of back
      pain, increasingly concentrate on the development and evaluation of interventions
      early after the onset of disease. This is complemented, on the one hand, by the
      development of clinical guidelines for the management of back pain in primary
      care and, on the other hand, by governmental policies aimed at reintegration of
      chronically ill in the labour force.

PMID- 10204733
TI  - Hyperalgesia with reduced laser evoked potentials in neuropathic pain.
AB  - Nociceptive evoked potentials to laser stimuli (LEPs) are able to detect lesions
      of pain and temperature pathways at peripheral, spinal and supraspinal levels. It
      is commonly accepted that LEP attenuation correlates with the loss of pain and
      temperature sensations, while pathological heat-pain hypersensitivity has been
      associated with increased LEP amplitude. Here we present two patients in whom
      increased pain sensation (hyperalgesia) to laser stimuli was, on the contrary,
      associated to delayed, desynchronized and attenuated LEPs. Both patients
      experienced increased unpleasantness and affective reactions to laser, associated
      to poor ability to localize the stimulus. In both cases the results may be
      explained by an overactivation of the 'medial pain system', in one patient due to
      deafferentation of cortical sensory areas by a capsular lesion, and in the other
      to imbalance between A-delta and C fiber excitation due to peripheral nerve
      injury. Our results suggest that LEPs, as currently recorded, reflect the
      activity of a 'lateral' pain system subserved by rapidly conducting fibers. They
      may therefore, assess the sensory and cognitive dimensions of pain, but may not
      index adequately the affective-emotional aspects of pain sensation conveyed by
      the 'medial' pain system. The dissociation between pain sensation and cortical
      EPs deserve to be added to the current semiology of LEPs, as the presence of
      abnormal pain to laser on the background of reduced LEPs substantiates the
      neuropathic nature of the pain.

PMID- 10204734
TI  - The effectiveness of spinal and systemic morphine on rat dorsal horn neuronal
      responses in the spinal nerve ligation model of neuropathic pain.
AB  - The treatment of pain arising from nerve injury can be difficult and the opioid
      sensitivity of neuropathic pain remains debatable. Clinical and animal studies
      report a wide range in the effectiveness of morphine, ranging from inadequate to
      potent analgesia. In this electrophysiological study we compare the effectiveness
      of spinal versus systemic administration of morphine on the natural and
      electrically evoked responses of spinal neurones of rats with a selective spinal
      nerve (L5/6) ligation. Recordings were made 1 week and/or 2 weeks after ligation.
      We have also compared the effects of morphine, by the two routes, on normal and
      sham operated animals. In spinal nerve ligated rats, morphine (0.1-5 microg)
      administered via the intrathecal route produced greater dose-dependent
      inhibitions of the neuronal responses compared with those produced by the
      systemic route (1-6 mg/kg). The dose response curves for intrathecal morphine on
      the C-fibre evoked and noxious natural stimuli evoked neuronal responses
      (mechanical and thermal) of spinal nerve ligated rats were to the left of those
      of sham operated and normal rats, suggesting an enhanced potency of intrathecal
      morphine after nerve injury. This was clearest for the lower doses of the opioid.
      The effects of spinal morphine on the responses to low intensity stimuli were
      similar in all groups of rats. In contrast to the spinal route, systemic morphine
      was less effective in inhibiting the evoked neuronal responses of spinal nerve
      ligated rats. This was especially clear for the C-fibre evoked and noxious
      natural stimuli evoked responses (mechanical and thermal) of spine nerve ligated
      rats. Our results suggest that the effectiveness of morphine may be partly
      related to the timing of the treatment relative to the duration of the
      neuropathy, the route of administration and also the neuropathic symptom. Spinal
      opioids may be a useful approach to pain control in neuropathic pain states where
      systemic routes produce inadequate analgesia.

PMID- 10204735
TI  - A comparison of 50, 100 and 200 mg of intra-articular pethidine during knee joint
      surgery, a controlled study with evidence for local demethylation to
      norpethidine.
AB  - Pethidine (meperidine) is a compound with both local anaesthetic and opioid
      agonist properties. We have in a recent study demonstrated that pethidine could
      be an interesting alternative to prilocaine in arthroscopy with local anaesthetic
      technique. Therefore, we investigated, in a controlled randomized double-blind
      study, the effect of three doses of pethidine compared with a standard local
      anaesthetic, in patients subjected to arthroscopic knee joint surgery. Ten
      patients in each group received 50 mg (P50), 100 mg (P100), 200 mg (P200) of
      pethidine or prilocaine (5 mg/ml) + adrenaline (4 mg/ml) (PC), injected intra
      articularly (i.a.) before surgery. We measured pain intensity and discomfort
      during arthroscopy and pain intensity at rest and at movement, nausea and
      tiredness for 3 days post-operatively at regular intervals using the VAS
      technique. We also measured the concentration of pethidine and its demethylated
      metabolite, norpethidine, in plasma by collecting blood samples at 20, 40, 60,
      80, 140 and 200 min following injection, and in synovial fluid which was
      collected through the arthroscope at the start and the end of the surgery. It was
      found that significantly more patients in the P50 group (n = 6) needed general
      anaesthesia due to intense pain than those in the P100 group (n = 1), P200 group
      (n = 0) or the PC group (n = 1). The PC group required significantly more
      analgesics and had a significantly higher calculated total sum of pain scores at
      movement post-operatively, than the other three groups. The P200 group more often
      reported tiredness post-operatively than the other three groups. We conclude that
      100 or 200 mg pethidine i.a. produces satisfactory anaesthesia for surgery. There
      was a rapid transfer of pethidine from synovial fluid to plasma, resulting in
      plasma levels earlier reported to produce centrally mediated effects, such as
      analgesia and tiredness. We found much higher concentrations of norpethidine in
      the synovial fluid than in plasma, suggesting a local demethylation in the knee
      joint tissues. This site of drug oxidation has not earlier been demonstrated
      neither in vitro nor in vivo. The results suggest that pethidine given i.a. in
      the dose range of 50 to 200 mg results in analgesia due to both peripheral and
      central mechanisms. The significant systemic uptake of pethidine can cause
      unwanted side-effects.

PMID- 10204736
TI  - The impact of clinical, morphological, psychosocial and work-related factors on
      the outcome of lumbar discectomy.
AB  - In a prospective controlled trial on 46 patients undergoing lumbar discectomy,
      three classes of variables (medical data including MRI-identified morphological
      abnormalities, general psychological factors and psychosocial aspects of work)
      were analyzed with regard to their predictive value for the outcome of lumbar
      disc surgery at 2 year follow-up. Multiple regression analyses were used to
      identify the best predictor variables of four different outcome measures (i.e.
      pain relief, reduction of disability in daily activities, return to work and
      surgical outcome). MRI-identified nerve root compromise and social support from
      the spouse were independent predictors of pain relief 2 years after surgery (R2 =
      0.40, P < 0.01). Return to work 2 years after surgery was best predicted by
      depression and occupational mental stress (R2 = 0.36, P < 0.001). MRI-identified
      extent of herniation and depression were significant predictors of a good
      surgical outcome after lumbar discectomy (R2 = 0.61, P < 0.001). This study has
      demonstrated that the outcome of discectomy is critically dependent on which
      outcome variables are selected and that different sorts of predictor variables
      have a distinct influence on the various outcome variables. Obvious morphological
      alterations (i.e. disc extrusions, nerve root compromise) proved to be
      significant predictors of postoperative pain relief and improvement of disability
      in daily activities justifying a surgical treatment approach in these cases. The
      most important finding of this study was that return to work was not influenced
      by any clinical findings or MR-identified morphological alterations, but solely
      by psychological factors (i.e. depression) and psychological aspects of work
      (i.e. occupational mental stress).

PMID- 10204737
TI  - Electroencephalographic responses to the formalin test in rats.
AB  - The formalin test is an animal model of persistent pain. Although biphasic
      behavioral responses to formalin injection have been well described, the
      significance of the biphasic time course of the pain behaviors has not been
      established. To explore the significance of the behavioral responses to the
      formalin injection, we measured and analyzed cortical electroencephalogram (EEG)
      during the formalin tests in rats. Formalin was injected subcutaneously in the
      hindpaw of freely moving rats, and behavioral responses were visually counted and
      recorded. Results were compared with a control group which received saline
      injection. Neocortical EEG was recorded from implanted dural surface electrodes
      and analyzed using a Fast Fourier Transformation. Formalin produced biphasic pain
      behaviors with a transient pause between two phases. Cortical EEG recordings
      showed a biphasic change; a vigilant pattern (a low amplitude high frequency
      activity) followed by a non-vigilant pattern (a high amplitude low frequency
      activity), showing a good correlation with apparent arousal states of rats.
      Observed discrepancies between pain behaviors and EEG-measured vigilance stages
      included (1) a vigilant EEG pattern persisted during the transient pause of pain
      behavior, and (2) pain behaviors persisted even after non-vigilant EEG pattern
      became dominant. The results of the current study showed that there are temporal
      discrepancies between the pain behaviors and EEG-measured vigilance during the
      formalin test in rats. The temporal relationship between the 'pain' behaviors and
      nociception per se may not be as solid as believed.

PMID- 10204738
TI  - The effect of compression and regional anaesthetic block on referred pain
      intensity in humans.
AB  - The mechanisms underlying local and referred muscle pain are poorly understood.
      The aim of this experiment was to determine to which degree referred pain is
      dependent on peripheral or central mechanisms. This was studied by blocking
      sensory input from the referred pain area. Intramuscular electrical stimulation
      in the right anterior tibial muscle induced local muscle pain and referred pain
      in 12 subjects. Nerve blocks were applied on the lower limb between the local and
      the referred pain area for 60 min. Three different studies were performed: (1) no
      nerve block (2) compression block, and (3) compression block combined with
      intravenous regional anaesthesia. The referred pain intensity was assessed every
      5 min. To monitor the blockade of myelinated and unmyelinated nerve fibres,
      touch, pinprick, position sense and heat and heat-pain detection thresholds were
      assessed on the dorsal side of the foot every 5 min. A significant reduction in
      referred pain intensity (40.5%) compared with the control experiment was found
      after 40 min with the compression ischemia nerve block until release of the
      tourniquet. In the combined nerve block experiment, a significant reduction of
      referred pain intensity (38.5%) was seen after 20 min and until the release of
      the tourniquet. There was no significant difference in the referred pain
      intensity between the two types of blocks. The present findings suggest that both
      peripheral and central mechanisms play a role in referred pain and that the
      myelinated fibres mediate the peripheral component.

PMID- 10204739
TI  - Painful and painless peripheral sensory neuropathies due to HIV infection: a
      comparison using quantitative sensory evaluation.
AB  - In order to characterize further, sensory disorders due to HIV-induced distal
      symmetrical polyneuropathy (DSPN), we compared quantitative sensory testing (QST)
      and electrodiagnostic parameters in patients presenting with painful or painless
      DSPN. Forty HIV patients with DSPN were studied and compared with ten
      seronegative control subjects: 15 patients presented with pains (spontaneous
      and/or evoked) in the lower limbs and 25 patients, matched for age, sex, duration
      of HIV and CD4 count, had non-painful symptoms (i.e. paresthesia). QST and nerve
      conduction studies (NCS) were performed on the lower limbs. von Frey hairs and a
      thermotest device were used to determine the mechanical- and thermal-, detection
      and pain thresholds. The responses elicited by suprathreshold thermal and
      mechanical stimuli were measured on a visual analog scale (VAS), to evaluate
      hyperalgesia. NCS were not significantly different between the two groups of
      patients. Thermal and mechanical detection thresholds, as well as the thermal
      pain threshold were significantly, and similarly, increased in both groups of
      patients as compared with the normal control subjects. Responses to
      suprathreshold thermal stimuli were similar in patients and control subjects. In
      contrast, mechanical pain thresholds were significantly decreased (mechanical
      allodynia) and responses to suprathreshold mechanical stimuli significantly
      increased (mechanical hyperalgesia) in the pain, but not in the painless
      patients. The intensity of mechanical allodynia/hyperalgesia was correlated with
      the intensity of spontaneous ongoing pain. We conclude that patients with DSPN
      are characterized by thermal, mechanical and electrophysiological deficits,
      suggestive of alterations in both small and large peripheral nerve fibers.
      Patients with a painful neuropathy present with static mechanical
      allodynia/hyperalgesia, suggestive of a selective alteration in the processing of
      mechanoreceptive signals, which might have a significant role in the
      pathophysiology of spontaneous and evoked pains in these patients.

PMID- 10204740
TI  - Immunocytochemical localization of P2X3 purinoceptors in sensory neurons in naive
      rats and following neuropathic injury.
AB  - P2X3 purinoceptor cellular distribution was studied in rat sensory neurons in
      naive animals and following peripheral nerve injury using immunohistochemical
      methods. Specific antiserum was raised in rabbits and characterized by Western
      blot, absorption assays and labeling of recombinant receptors. In naive animals,
      P2X3 immunoreactivity was present predominantly in a subpopulation of small
      diameter sensory neurons in dorsal root ganglia. In the spinal cord,
      immunoreactivity was observed in the superficial laminae of the dorsal horn.
      Following a chronic constriction injury to the sciatic nerve, the number of P2X3
      positive small and medium diameter neurons increased in dorsal root ganglia when
      compared with sham-operated animals. In addition, the spinal cord
      immunoreactivity increased in magnitude on the side ipsilateral to the ligated
      nerve, consistent with up-regulation of receptors in presynaptic terminals of the
      primary sensory neurons.

PMID- 10204741
TI  - Behavioral dimensions of adjustment in persons with chronic pain: pain-related
      anxiety and acceptance.
AB  - Through empirical methods we now characterize patients with chronic pain as
      either dysfunctional, interpersonally distressed, or adaptive copers. Studying
      factors that differentiate these groups may reveal the behavioral processes that
      determine adjustment to pain. Subjects for this study were 190 patients referred
      for treatment of chronic pain. They were classified as dysfunctional (n = 41),
      interpersonally distressed (n = 28) or adaptive copers (n = 59) based on the
      Multidimensional Pain Inventory (Kerns, R.D., Turk, D.C. and Rudy, T.E., The West
      Haven-Yale Multidimensional Pain Inventory (WHYMPI), Pain, 23 (1985) 345-356) and
      compared on measures of pain-related anxiety and pain acceptance. Our analyses
      showed that the dysfunctional group reported greater pain-related anxiety and
      less acceptance of pain than the other groups. Additional analyses, statistically
      controlling for pain severity and depression, showed that the patient subtypes
      continued to differ on pain-related anxiety and acceptance. Discriminant function
      analyses including pain-related anxiety and acceptance correctly classified 72.5%
      of dysfunctional and 90.9% of adaptive copers. Again, anxiety and acceptance
      contributed uniquely to classification independent of depression and pain
      intensity. Pain-related anxiety and acceptance of pain appear to be unique
      behavioral dimensions of adjustment to chronic pain. Decreasing anxiety and
      increasing acceptance may 'move' patients with chronic pain from the
      dysfunctional to the adaptive coper category.

PMID- 10204742
TI  - Nicotinic cholinergic receptors: potential targets for inflammatory pain relief.
AB  - We have shown previously that the development of hyperalgesia and inflammation
      associated with knee joint arthritis depends on interactions among various
      receptors in the central and peripheral nervous system in addition to the
      contribution of blood borne inflammatory mediators. In the present study, the
      involvement of spinal nicotinic cholinergic receptors in the modulation of
      inflammatory pain was evaluated using a model of acute arthritis in rats.
      Epibatidine (EP), a potent agonist for neuronal nicotinic acetylcholine receptors
      sharing similar structural and functional characteristics with acetylcholine and
      nicotine, has been used in this study. The physiological effects of EP on pain
      related behaviors and inflammation were tested after administration to the dorsal
      horn via a microdialysis fiber. Knee joint inflammation was induced in rats by
      injecting a mixture of kaolin and carrageenan into the knee joint. Paw withdrawal
      latency to radiant heat was measured before and at 4, 5, 6, 7 and 8 h after
      induction of inflammation. The decrease in PWL in this arthritis model is
      indicative of secondary hyperalgesia. The extent of peripheral inflammation was
      also assessed by measuring knee joint circumference and temperature. Treatment of
      the spinal cord of animals with EP prior to induction of arthritis attenuated the
      development of heat hyperalgesia and resulted in a significant improvement of the
      animals' spontaneous pain-related behaviors. More interestingly, the knee joint
      circumference and temperature of these animals were also significantly lower than
      those of the control animals when measured at 8 h. Likewise, spinal
      administration of epibatidine after the development of hyperalgesia not only
      significantly attenuated the decrease in PWL, but prevented further increases in
      knee joint swelling and temperature. The antinociceptive effect of epibatidine
      was selectively blocked by the nicotinic receptor antagonist, mecamylamine. Joint
      circumference and temperature were not selectively altered by mecamylamine
      suggesting another mechanism involving non-nicotinic receptors in the spinal
      regulation of joint inflammatory responses. Collectively, these findings provide
      considerable evidence to suggest an important role for central nicotinic
      cholinergic receptors in the modulation of persistent pain and neurogenic
      inflammation mediated by events in the dorsal horn.

PMID- 10204743
TI  - Spinal neurokin3 receptors facilitate the nociceptive flexor reflex via a pathway
      involving nitric oxide.
AB  - The present study examined the effects of intrathecal administration of
      neurokinin3 receptor agonists on the electrically-evoked nociceptive flexor
      reflex in decerebrate and spinalized adult rats. The reflex was evoked by
      stimulating the isolated sural nerve at an intensity that activates C fibers and
      was measured by recording the number of compound potentials in the ipsilateral
      hamstring muscles. Intrathecal senktide (1-30 nmol), a neurokinin3 receptor
      agonist, dose-dependently facilitated the reflex reaching a maximum effect of
      230% of the baseline reflex at 10 nmol. SR 142801 (60 nmol), a non-peptide
      neurokinin3 receptor antagonist, blocked facilitation of the reflex induced by 10
      nmol senktide, providing further support that the effect of senktide is mediated
      by neurokinin3 receptors. The intrathecal administration of senktide (10 nmol)
      did not alter the monosynaptic reflex elicited by stimulating the L5 dorsal root
      at an intensity that was at the threshold for activating A fibers. This indicates
      that the senktide-induced facilitation of the nociceptive flexor reflex was not
      at the level of the motor neuron. Pretreatment with N(G)-nitro-L-arginine methyl
      ester (30 nmol), a nitric oxide synthase inhibitor, attenuated the effect of
      senktide, indicating that facilitation of the reflex by senktide is also mediated
      by the production of nitric oxide. Data from the present work have shown that
      spinal neurokinin3 receptors facilitate the nociceptive flexor reflex through a
      pathway that involves interneurons and the production of NO. Therefore,
      neurokinin3 receptors are likely to be involved in enhancing nociceptive
      neurotransmission at the level of the spinal cord.

PMID- 10204744
TI  - Spinal neurokinin3 receptors mediate thermal but not mechanical hyperalgesia via
      nitric oxide.
AB  - Although intrathecally administered senktide, an agonist at the neurokinin3
      receptor, attenuates withdrawal responses to noxious stimuli in the restrained
      animal, senktide increases motor neuron activity in spinal cords of neonatal rats
      and facilitates the electrically-evoked nociceptive flexor reflex in the adult
      rat. The present study examined the effects of intrathecal administration of
      senktide on withdrawal responses to noxious thermal and mechanical stimuli in
      awake, unrestrained, adult rats. Intrathecal administration of senktide (10 nmol)
      in chronically catheterized rats did not alter the responses elicited by a
      noxious mechanical stimulus (508 mN, von Frey monofilament). Conversely,
      intrathecal senktide (10 nmol) induced thermal hyperalgesia, indicated by
      decreased withdrawal latency to radiant heat. Thermal hyperalgesia peaked 20-26
      min following drug injection and returned to normal within 30 min. SR 142801 (60
      nmol), a non-peptide neurokinin3 receptor antagonist, inhibited the senktide
      induced hyperalgesia, providing further support that the effect of senktide is
      mediated by neurokinin3 receptors. Pretreatment with N(G)-nitro-L-arginine methyl
      ester (30 nmol), a nitric oxide synthase inhibitor, blocked the effect of
      senktide, indicating that senktide-induced thermal hyperalgesia is also mediated
      by the production of nitric oxide. Intrathecal senktide produced vasodilation and
      increased skin temperature in the hind paw. Intravenous hexamethonium, a
      ganglionic nicotinic receptor antagonist, similarly increased paw temperature
      without decreasing withdrawal latency to radiant heat. Thus, the increased skin
      temperature associated with intrathecal senktide was insufficient to account for
      the thermal hyperalgesia observed. Collectively, the present work demonstrates
      that NK3 receptors mediate thermal but not mechanical hyperalgesia through a
      pathway that involves the production of NO.

PMID- 10204745
TI  - Traction on the mesentery as a model of visceral nociception.
AB  - Traction of the mesentery is known to induce strong autonomic reactions in
      patients undergoing abdominal surgery. An experimental model using this stimulus
      in anaesthetized rats has been developed, which allows the comparison of noxious
      mechanical and chemical stimulation of the mesentery. Graded traction on a bundle
      of jejunal vessels with 2-30 g led to reflex changes in blood pressure and
      intragastric pressure, the size of which correlated with the strength of the
      stimulus. Comparable responses were elicited by clamping the same vessels either
      at their distal or proximal end or by applying 100 microl 0.6% acetic acid or 0.
      microM bradykinin. These reflexes are fairly insensitive towards impairment of
      the autonomic system. Only the combination of phentolamine and propranolol
      reduced the cardiovascular responses to all stimuli but at the same time,
      significantly lowered basal blood pressure. The adrenoceptor antagonists affected
      the gastric response to acid only. Atropine on its own was ineffective.
      Administered together with the combination of adrenoceptor blockers it had no
      further influence on the cardiovascular reflexes but significantly reduced the
      gastric responses to stretch, proximal clamping and acid. Acute desensitization
      of small diameter afferents with capsaicin almost abolished the reflex responses
      to acid. The cardiovascular, but not the gastric, response to traction was
      reduced by capsaicin. Morphine led to dose-dependent reductions of the reflex
      responses in a naloxone-reversible manner, whereas indomethacin was inactive. The
      bradykinin B2-antagonist icatibant abolished the reflex in response to the
      application of bradykinin but not to acid or traction. It is concluded that the
      measurement of the cardiovascular and gastric responses of anaesthetized rats to
      traction on the mesentery is a suitable method to investigate acute visceral
      nociception. Chemical stimuli to the mesentery are transmitted by capsaicin
      sensitive afferents, but there is a dichotomy regarding capsaicin's influence on
      visceral mechanonociception. Opioid mechanisms are always involved, whereas
      prostaglandins or bradykinin have no role in the reflexes evoked by acid or
      traction. Intact alpha- or beta-adrenergic (as tested with unselective receptor
      antagonists) or muscarinic mechanisms are required for the reaction of the end
      organs in the reflex but they have no role in the afferent or central processing.

PMID- 10204746
TI  - Pain-related fear is more disabling than pain itself: evidence on the role of
      pain-related fear in chronic back pain disability.
AB  - There is growing evidence for the idea that in back pain patients, pain-related
      fear (fear of pain/physical activity/(re)injury) may be more disabling than pain
      itself. A number of questionnaires have been developed to quantify pain-related
      fears, including the Fear-Avoidance Beliefs Questionnaire (FABQ), the Tampa Scale
      for Kinesiophobia (TSK), and the Pain Anxiety Symptoms Scale (PASS). A total of
      104 patients, presenting to a rehabilitation center or a comprehensive pain
      clinic with chronic low back pain were studied in three independent studies aimed
      at (1) replicating that pain-related fear is more disabling than pain itself (2)
      investigating the association between pain-related fear and poor behavioral
      performance and (3) investigating whether pain-related fear measures are better
      predictors of disability and behavioral performance than measures of general
      negative affect or general negative pain beliefs (e.g. pain catastrophizing). All
      three studies showed similar results. Highest correlations were found among the
      pain-related fear measures and measures of self-reported disability and
      behavioral performance. Even when controlling for sociodemographics, multiple
      regression analyses revealed that the subscales of the FABQ and the TSK were
      superior in predicting self-reported disability and poor behavioral performance.
      The PASS appeared more strongly associated with pain catastrophizing and negative
      affect, and was less predictive of pain disability and behavioral performance.
      Implications for chronic back pain assessment, prevention and treatment are
      discussed.

PMID- 10204748
TI  - Are there long-term changes in the basal or evoked Fos expression in the dorsal
      horn of the spinal cord of the mononeuropathic rat?
AB  - The long-term changes in Fos like-immunoreactivity (Fos-LI) in the dorsal horn of
      the spinal cord following various peripheral nerve lesions remain controversial.
      This study considers such an approach with chronic constriction injury rats (CCI:
      loose ligations of the sciatic nerve), at 2 weeks after the surgery, when changes
      in spontaneous and evoked behaviour were clearly described. All rats used for Fos
      studies displayed allodynia to mechanical stimulation (decrease of 32% of the
      vocalization threshold to paw pressure). In CCI rats, which displayed
      'spontaneous pain-related behaviour', the number of Fos-LI neurones, in the
      absence of any intentional stimulation, was very low and comparable with that
      observed in normal and sham-operated rats (<10 neurones/40 microm section). Thus,
      in this model, the expression of Fos protein is not a reliable index of
      spontaneous pain. Surprisingly, despite the fact that in this model numerous
      anatomical studies described a dramatic loss of large and unmyelinated primary
      afferent fibers, we were unable to detect changes in the number and distribution
      of Fos-LI evoked by various modalities of peripheral noxious stimulation (noxious
      thermal stimuli, noxious mechanical stimuli and carrageenin induced
      inflammation). For example, the stimulus-response curves for the number of Fos-LI
      neurones evoked by a series of heat stimuli (40, 45, 48, 52, 55 degrees C) were
      almost superimposable for CCI, sham-operated and normal rats. In contrast,
      stroking of the nerve-injured paw induced a significant expression of Fos-LI in
      the superficial laminae (I-II) of the dorsal horn of CCI rats (19.5 +/-
      3/sections, P = 0.027) which was greater than that observed in sham-operated (6.5
      +/- 3/sections) or in normal rats (3.5 +/- 2/section). These modifications may
      reflect mechanical allodynia observed in behavioural studies and could be related
      to A beta fibers, which are known to be severely affected after the constriction
      of the nerve. These results suggest that this approach could be useful to study,
      at the cellular level, in freely moving rats, some pharmacological aspects of
      neuropathic pain.

PMID- 10204747
TI  - Behavioural measures of depression and anxiety in rats with spinal nerve ligation
      induced neuropathy.
AB  - The behaviour of rats with spinal nerve ligation-induced neuropathic pain was
      studied using tests developed to measure depression and anxiety. Adult male
      Sprague-Dawley rats were tested with the open field test, elevated plus maze, two
      compartment test and forced swimming test. Spontaneous motility was measured in a
      photocell observation box. Mechanical sensitivity was tested with von Frey hairs
      and cold sensitivity with the acetone drop test. The L5-6 spinal nerves were
      ligated or a sham operation was performed and the rats were followed for 2 weeks
      before the same set of tests were repeated. Most of the neuropathy operated rats
      had mechanical and cold allodynia. With post-injury there was a significant
      decrease in the activity in the open field test and motility box tests, when
      compared with the pre-injury results. In the elevated plus maze test there was a
      significant reduction in the motility, but there was no change in the time spent
      in the closed wings. In the two compartment test there were no significant
      differences between the pre- and post-injury results. There were no differences
      between the rats with spinal nerve ligation injury and the sham operated rats in
      any of the tests. The results were also comparable when rats that developed a
      high degree of neuropathy were compared with the rats with low degree of
      neuropathy and the sham operated group. In conclusion, spinal nerve ligation
      injury of the spinal nerves L5-6 induces mechanical and cold allodynia, but it
      does not seem to produce general suffering or measurable anxiety to the animals.
      Furthermore, tests for anxiety and depression were not able to predict which
      animals were vulnerable to express symptoms of neuropathic pain after nerve
      injury.

PMID- 10204749
TI  - Pain sensitivity, cerebral laterality, and negative affect.
AB  - The right hemisphere is assumed to play a unique role for pain sensitivity and
      negative affect. Pressure pain thresholds were assessed daily in eight right
      handed participants over a 6-week period in order to obtain reliable measures of
      pain sensitivity unaffected by situational influences. In an additional session,
      cerebral laterality was assessed with behavioral and an EEG measures.
      Psychometric measures were used to examine emotionality (depression,
      neuroticism). Pain thresholds were lower on the left compared with the right
      hand, and pain thresholds increased within the first 3-measurement weeks.
      Enhanced pain sensitivity as reflected in weekly pain threshold was associated
      with a increased right frontal compared with left frontal brain activity as
      indicated by EEG, with a left-visual field advantage in the perception of
      emotional faces, and with increased negative affect (depression, neuroticism). In
      addition, a significant positive correlation between a relatively increased right
      frontal brain activity and depression was found. Correlations between pain
      thresholds and 'non-emotional' laterality measures (central or parietal EEG
      asymmetry, dichotic consonant-vocal-recall test) were not significant. We
      conclude that a right frontal brain hyperactivity might be a biological marker
      for enhanced pain sensitivity and negative affect.

PMID- 10204750
TI  - Patient utilities in chronic musculoskeletal pain: how useful is the standard
      gamble method?
AB  - The main goal of current pain management approaches is to increase the patients'
      quality of life by improving pain coping skills and by reducing the levels of
      disability in daily life, often despite persistent pain. Direct measurement of
      quality of life is of crucial importance in economic evaluation research, in
      which not only is the estimation of financial costs and benefits included, but so
      is the evaluation of costs and benefits in terms of changes in health states. The
      purpose of this study is to compare the psychometric qualities of two instruments
      for assessing patients' utilities, the rating scale (RS) and the standard gamble
      (SG). Such instruments are designed for their application in economic evaluation
      research, but have seldomly been used in chronic pain trials. Both methods
      provide a single measure between 0 and 1. The relationship between these utility
      measures and descriptive and domain-specific quality of life measures was
      examined in 133 fibromyalgia patients and 148 patients with chronic non-specific
      low back pain. Mean utility score at baseline was 0.43 with the RS and 0.78 for
      the SG. The correlation between both methods was found to be poor (r = 0.21).
      Both measures appeared to be fairly stable in a 2-week test-retest period (intra
      class correlation coefficient (ICC) = 0.74 and 0.77). Scores on the description
      of patient's own health on six domains, global assessment of change and domain
      specific measures correlated moderately with the RS scores and low with the SG.
      Multiple regression analyses demonstrated that 32% of the variance in RS values
      and only 13% of the variance in SG utilities could be explained by domain
      specific measures. These results suggest an acceptable construct validity for the
      RS but insufficient construct validity for the SG. Valuations of ones own health
      appear only partially to be related to the assessment of the pain-specific
      measures and measures of distress. It can be concluded that the RS and domain
      specific measures assess partly different, but nevertheless complementary aspects
      of health-related quality of life. It is therefore recommended to include in
      economic evaluation studies both domain-specific measures and valuation measures.
      Finally, in chronic musculoskeletal pain patients, RS scores were found to be
      more responsive in detecting significant changes in preferences than SG scores.
      For use in patients with chronic musculoskeletal pain, the RS is preferred to the
      SG for establishing accurate decisions about the impact of new interventions on
      their health outcomes.

PMID- 10204751
TI  - Pain threshold and tolerance in Alzheimer's disease.
AB  - We tested both pain thresholds and pain tolerance in patients with Alzheimer's
      disease (AD) by means of phasic and tonic noxious stimuli. In the first case,
      electrical stimulation was used, whereas in the second case arm ischemia was
      studied. By comparing AD patients with normal subjects of the same age, we found
      no differences in stimulus detection and pain thresholds, whereas a clearcut
      increase in pain tolerance was present in AD patients. The severity of AD was
      assessed by means of the Mini Mental State Examination test (MMSE) and the
      spectral analysis of the electroencephalogram (EEG). There was a straightforward
      correlation between MMSE scores and pain tolerance such that the more severe the
      cognitive impairment the higher the tolerance to pain. In addition, analysis of
      the EEG power spectra indicated that patients with low alpha and high delta peaks
      showed an increase in pain tolerance to both electrical stimulation and ischemia.
      These findings show that, whereas the sensory-discriminative component of pain is
      maintained in AD patients, pain tolerance is altered and depends on cognitive and
      affective factors. Thus, pain tolerance is tightly related to the severity of the
      disease according to the rule, 'the more severe the MMSE and EEG changes, the
      higher the tolerance to pain'.

PMID- 10204752
TI  - Enadoline, a selective kappa-opioid receptor agonist shows potent
      antihyperalgesic and antiallodynic actions in a rat model of surgical pain.
AB  - Enadoline is a highly selective and potent kappa-opioid receptor agonist. This
      report describes and compares the activities of enadoline and morphine in a rat
      model of postoperative pain. A 1 cm incision through the muscle and skin of the
      plantar surface of the right hind paw induced thermal hyperalgesia as well as
      static and dynamic allodynia lasting at least 2 days. Postoperative testing was
      carried out using the plantar test for thermal hyperalgesia, von Frey hairs for
      static allodynia and light stroking with a cotton bud for dynamic allodynia. A
      single i.v. dose of enadoline 15 min before surgery dose-dependently (1-100
      microg/kg) blocked the development of thermal hyperalgesia as well as static and
      dynamic allodynia for over 24 h with respective MEDs of < or = 1, 10 and 10
      microg/kg. The administration of enadoline (100 microg/kg, i.v.), 1 h after
      surgery, completely blocked the maintenance of the hyperalgesic and allodynic
      responses, but its duration of action was much shorter (2 h) than when
      administered before surgery. Previous studies have shown that administration of
      morphine (1-6 mg/kg, s.c.) 0.5 h before surgery can prevent the development of
      thermal hyperalgesia with a MED of < or =1 mg/kg, but it has little effect on
      static allodynia. In the present study similar administration of morphine (1-3
      mg/kg), unlike enadoline, had no effect on the development of dynamic allodynia.
      Morphine dose-dependently (1-6 mg/kg, s.c.) potentiated isoflurane-induced
      sleeping time and respiratory depression in the rat. However, whilst enadoline
      also (1-1000 microg/kg, i.v.) potentiated isoflurane-induced sleeping time, it
      did not cause respiratory depression. It is suggested that enadoline may possess
      therapeutic potential as a pre-emptive antihyperalgesic and antiallodynic agent.

PMID- 10204753
TI  - Gabapentin and pregabalin, but not morphine and amitriptyline, block both static
      and dynamic components of mechanical allodynia induced by streptozocin in the
      rat.
AB  - A single injection of streptozocin (50 mg/kg, i.p.) led to the development of
      static and dynamic allodynia in the rat. The two responses were detected,
      respectively, by application of pressure using von Frey hairs or lightly stroking
      the hind paw with a cotton bud. Static allodynia was present in the majority of
      the animals within 10 days following streptozocin. In contrast, dynamic allodynia
      took almost twice as long to develop and was only present in approximately 60% of
      rats. Morphine (1-3 mg/kg, s.c.) and amitriptyline (0.25-2.0 mg/kg, p.o.) dose
      dependently blocked static allodynia. However, neither of the compounds was
      effective against dynamic allodynia. In contrast, gabapentin (10-100 mg/kg, p.o.)
      and the related compound pregabalin (3-30 mg/kg, p.o.) dose-dependently blocked
      both types of allodynia. However, the corresponding R-enantiomer (10-100 mg/kg,
      p.o.) of pregabalin, was found to be inactive. The intrathecal administration of
      gabapentin dose-dependently (1-100 microg/animal) blocked both static and dynamic
      allodynia. In contrast, administration of similar doses of gabapentin into the
      hind paw failed to block these responses. It is suggested that in this model of
      neuropathic pain dynamic allodynia is mediated by A beta-fibres and the static
      type involves small diameter nociceptive fibres. These data suggest that
      gabapentin and pregabalin possess a superior antiallodynic profile than morphine
      and amitriptyline, and may represent a novel class of therapeutic agents for the
      treatment of neuropathic pain.

PMID- 10204754
TI  - Nefopam strongly depresses the nociceptive flexion (R(III)) reflex in humans.
AB  - Nefopam hydrochloride has been commercialized as an analgesic drug in most
      Western European countries for 20 years. It has been shown to possess analgesic
      activity with a profile distinct from that of opioids or anti-inflammatory drugs.
      In order to define the mechanisms of action of this pharmacological agent, we
      studied, in a double-blind and cross-over fashion, its effects on the nociceptive
      flexion (R(III)) reflex and the corresponding pain sensation in ten healthy
      volunteers. The R(III), reflex elicited by electrical stimulation of the sural
      nerve was recorded from the biceps femoris. Two experiments were performed on
      each volunteer at an interval of 7 days. On each experimental day, four
      recruitment (intensity-response) curves of the R(III) reflex were constructed:
      before (control period) and then 30, 60 and 90 min after the intravenous
      injection of nefopam (20 mg) or a placebo. Nefopam induced a powerful depression
      of the nociceptive R(III) reflex. It increased the threshold of the reflex and
      decreased the slope of the recruitment curve. At the same time, it decreased the
      painful sensations (as measured with a visual analogue scale(VAS)) elicited by
      the maximum stimulus intensity. These data suggest that nefopam probably produces
      its analgesic action through central (spinal and/or supraspinal) mechanisms.
      However, complementary peripheral mechanisms cannot be excluded on the basis of
      the present study. In view of these results, it seems that new clinical studies
      will have to be undertaken to revisit this potent analgesic agent and try to
      limit its adverse effects (i.e. nausea, vomiting, sweating). Its fast onset of
      action could clearly be an advantage, notably in the treatment of post-operative
      pain.

PMID- 10204755
TI  - Nitroprusside inhibits thermal hyperalgesia induced by noradrenaline in capsaicin
      treated skin.
AB  - A facilitatory effect of the sympathetic neurotransmitter noradrenaline on
      nociceptor discharge may sometimes contribute to pain and hyperalgesia in
      inflammatory and neuropathic pain syndromes. Our previous studies have shown that
      noradrenaline heightens sensitivity to heat in skin sensitized by the topical
      application of capsaicin, and that this effect persists during arterial occlusion
      (Drummond, P.D., Noradrenaline increases hyperalgesia to heat in skin sensitized
      by capsaicin, Pain, 60 (1995) 311-315; Drummond, P.D., Independent effects of
      ischaemia and noradrenaline on thermal hyperalgesia in capsaicin-treated skin,
      Pain, 67 (1996) 129-133). In the present study, the hyperalgesic effects of
      arterial occlusion and the vasodilators nitroprusside and isoprenaline were
      investigated in the capsaicin-treated skin of healthy subjects, to determine
      whether adrenergic vasoconstriction contributes to thermal hyperalgesia. Thermal
      hyperalgesia intensified during arterial occlusion; however, sites of
      noradrenaline iontophoresis were more sensitive to heat than elsewhere in the
      capsaicin-treated skin, even when noradrenaline was administered during arterial
      occlusion. Nitroprusside inhibited adrenergic hyperalgesia except during arterial
      occlusion, suggesting that the analgesic effect of nitroprusside was mediated by
      vasodilatation. The beta-adrenoceptor agonist isoprenaline did not antagonize the
      vasoconstrictive or hyperalgesic effects of noradrenaline, and did not influence
      thermal hyperalgesia elsewhere in the capsaicin-treated skin. These findings
      favour an ischaemic mechanism of adrenergic hyperalgesia in skin sensitized by
      capsaicin. An additional mechanism, independent of skin perfusion, is needed to
      account for the development of adrenergic hyperalgesia during arterial occlusion.

PMID- 10204756
TI  - Inhibition of evoked C-fibre responses in the dorsal horn after contralateral
      intramuscular injection of capsaicin involves activation of descending pathways.
AB  - In this study extracellular recordings of nociceptive dorsal horn neurones driven
      by electrical stimulation of the sciatic nerve were performed in intact urethane
      anaesthetized Sprague-Dawley rats. Spikes 0-40, 40-250 and 250-800 ms after
      stimulus were defined as A- and C-fibre responses and post-discharge,
      respectively, and the effect of 200 microg capsaicin (8-methyl-N-vanillyl-6
      noneamide) injected into the contralateral gastrocnemius-soleus muscle was
      investigated. In most cells tested, regardless of the size or location of their
      receptive fields, the injection of capsaicin caused a clear inhibition of the
      electrically evoked C-fibre responses. In animals with intact descending pathways
      the mean C-fibre response was inhibited to 51% of baseline 15 min after injection
      of capsaicin. In contrast, when capsaicin was given during cold block of the
      spinal cord between the brainstem and the site of recording in the dorsal horn,
      the same response was inhibited to 91% of baseline. A significant interaction
      between cold block and capsaicin was detected. We conclude that stimulation of
      capsaicin-sensitive afferents in the deep tissue in the hind limb can inhibit the
      electrically evoked C-fibre responses in the dorsal horn by activating inhibitory
      descending projections from higher centres. The model presented here may be an
      important tool for further investigations of the endogenous descending
      antinociceptive system.

PMID- 10204757
TI  - Neurotoxicity of midazolam in the rabbit.
AB  - Safe and efficient use of spinal drugs requires neurotoxicologic animal studies
      before ethical application. We have evaluated the neurotoxicologic interruptions
      of intrathecal administration of midazolam in rabbits. Eighteen white New Zealand
      rabbits were randomly assigned into three groups consisting of six rabbits each.
      In conscious animals, 0.3 ml 0.9% normal saline solution, 0.3 ml 0.1% midazolam
      (Roche, Dormicum) or 0.3 ml preservative free midazolam were intrathecally
      administered. Light and fluorescence microscopy evaluations were performed on
      transverse spinal cord sections by a neurohistopathologist in a blind fashion.
      Midazolam and preservative free midazolam treated rabbits showed significant
      histologic changes in light and fluorescence microscopy. The histologic and
      vascular lesions with the use of midazolam and preservative free midazolam
      suggested neurotoxic effects; thus chronic intrathecal administration of
      midazolam should be avoided in humans.

PMID- 10204758
TI  - The relationship of arthritis self-efficacy to daily pain, daily mood, and daily
      pain coping in rheumatoid arthritis patients.
AB  - There is an increasing awareness in the medical community that psychosocial
      variables such as beliefs in self-efficacy are important determinants of
      treatment outcome. However, before measures of self-efficacy are widely
      incorporated into clinical practice, there needs to be a better understanding of
      how they relate to daily pain, mood and coping. In the present study 128
      rheumatoid arthritis patients completed diaries for 30 days in which they
      provided daily ratings of joint pain, negative and positive mood, the use of pain
      coping strategies, and coping efficacy. The patients then participated in an
      evaluation session during which measures of self-efficacy (the Arthritis Self
      Efficacy Scale (ASES)), demographic variables, and medical status were collected.
      A series of hierarchical regression analyses was conducted to determine the
      degree to which self-efficacy measures collected at the time of the evaluation
      session were related to daily diary measures collected during the 30 preceding
      days. The results revealed that self-efficacy was significantly related to daily
      ratings of pain, mood, coping and coping efficacy. Interestingly, the findings
      regarding self-efficacy were obtained even after taking into account the effects
      of important demographic and medical status variables. Taken together, these
      results suggest that self-efficacy ratings collected from arthritis patients at
      the time of an evaluation session may well be related to recent experiences of
      daily pain and mood, as well as the daily use and perceived effectiveness of pain
      coping strategies.

PMID- 10204759
TI  - The longer term effect of pulsed radiofrequency for neuropathic pain.
AB  - Pulse radiofrequency has been recently described as a technique to apply a
      relatively high voltage near a nerve but without the usual effects of a rise in
      temperature or subsequent nerve injury. In this set of case reports, the effect
      of pulsed radiofrequency (PRF) is described in patients with neuropathic pain
      syndromes which have been poorly controlled with other oral and invasive
      treatments. Whilst anecdotal, the results have been remarkable and should
      encourage further research into this technique. Observations from the basic
      science tend to support the concept that PRF may induce some sort of long-term
      depression in the spinal cord.

PMID- 10204760
TI  - Successful treatment of whiplash-type injury induced severe pain syndrome with
      epidural stimulation: a case report.
AB  - Chronic severe cervico-facial pain syndrome associated with a whiplash-type
      injury was successfully treated with epidural spinal cord stimulation. The
      patient had been in pain for 9 years, responding temporarily only to stellate
      ganglion blocks. The patient has now been painless for 18 months. We have been
      unable to find a similar case reported in the literature to date.

PMID- 10204761
TI  - Central pain as a manifestation of partial epileptic seizures.
AB  - Central pain of epileptic etiology is very rare. The frequency of painful
      sensations in epileptic seizures varies between 0.3 and 2.8%. We report a patient
      with short-lasting painful attacks in the right arm. Changes in the
      electroencephalography (EEG) and the effective treatment with anticonvulsants in
      contrast to the therapeutic failure of analgesics, lead to the diagnosis of
      partial epilepsy with painful seizures. Magnetic resonance imaging (MRI) of the
      brain was normal, whereas a postcentral parietal site of seizure origin involving
      the secondary somatosensory area was suggested by electroencephalographic
      findings. The literature is reviewed for cases with pain as the sole or
      predominant symptom of epileptic seizures.

PMID- 10204762
TI  - Reply to M.I. Weintraub.

PMID- 10204763
TI  - The influence of visual illusions on grasp position.
AB  - Visual size illusions have been shown to affect perceived object size but not the
      aperture of the hand when reaching to those same objects. Thus, vision for
      perception is said to be dissociated from vision for action. The present study
      examines the effect of visual-position and visual-shape illusions on both the
      visually perceived center of an object and the position of a grasp on that object
      when a balanced lift is required. The results for both experiments show that
      although the illusions influence both the perceived and the grasped estimates of
      the center position, the grasp position is more veridical. This partial
      dissociation is discussed in terms of its implications for streams of visual
      processing.

PMID- 10204765
TI  - Perceptual distortions in the neural representation of visual space.
AB  - The visual mechanism by which human observers determine the separation between
      objects has long been of interest. This study examines the extent to which
      separation in visual space can be misperceived in foveal and extrafoveal vision.
      Foveally, vertical separations were consistently overestimated relative to
      horizontal separations, a result which is consistent with the well-documented
      horizontal-vertical illusion (HVI). Extrafoveally, much larger misrepresentations
      of visual space were perceived. In addition, separations tangential to fixation
      were consistently perceived as being greater than separations in a radial
      direction. These marked misperceptions of visual space which occur in extrafoveal
      vision take the form of a radial/tangential anisotropy combined with an
      overestimation of vertical distance. The results have important implications for
      meridional anisotropies which have previously been documented in a number of
      visual performance tasks.

PMID- 10204764
TI  - Drawing under visuomotor incongruence.
AB  - Six human subjects were asked to draw ellipses presented on a screen by moving a
      manipulandum that controlled the position of a cursor. Six visual templates were
      used, which comprised three different ellipses displayed either horizontally or
      vertically; the ratio between the major and minor axes was 2, 4, or 5. For each
      visual template, the gains were set such that the movement trajectories required
      to trace the template with the cursor corresponded to one of six ellipses. Thus
      these movement ellipses were horizontal or vertical with a ratio between major
      and minor axes of 2, 4, or 5. All 36 combinations of six visual ellipses and six
      required movement ellipses were used. Therefore, in some conditions the required
      movement ellipse had a different orientation (with respect to the major axis)
      than the visual template. These conditions were called orientation incongruent,
      whereas, when the orientation of the required movement ellipse matched the
      orientation of the visual template, the conditions were called orientation
      congruent. Similarly, eccentricity incongruent referred to conditions where the
      eccentricities of the visual ellipse and the required movement ellipse were
      different, as opposed to eccentricity congruent. The main results were as
      follows: (a) The perimeter of the traced ellipse always tended to be larger than
      that of the visual template. In addition, it was significantly larger in the
      orientation incongruent conditions than in the orientation congruent conditions.
      Nevertheless, the perimeter of the traced figure increased with the template in
      both orientation congruent and incongruent conditions. (b) The shape of the
      traced figure varied appropriately with the visual template, but differed
      significantly between the orientation congruent and incongruent conditions. It
      was closer to the one of the template in the orientation congruent than in the
      incongruent conditions. Finally, (c) the instantaneous speed was significantly
      correlated with curvature but more tightly so in the orientation congruent than
      in the orientation incongruent conditions. The parameters defining the relation
      between speed and curvature were affected by the required movement ellipse, but
      not by the particular visuomotor condition. These results showed that although
      spatial motor performance was affected by changes in the correspondence between
      visual and movement coordinates, the relation between the speed and curvature of
      the movement trajectory was stable despite drastic changes in this
      correspondence.

PMID- 10204766
TI  - Neuronal pathways for spinal reflexes activated by group I and group II muscle
      afferents in the spinal segment (Co1) innervating the tail in the low spinalized
      cat.
AB  - We studied neuronal pathways for spinal reflexes activated by group-I and group
      II muscle afferents in the spinal segments innervating the tail in unanesthetized
      and spinalized (L1) cats. Experiments were performed on 25 adult cats of both
      sexes. The effects of stimulating nerves innervating six tail muscles on both
      sides were recorded from tail motoneurons in the first coccygeal spinal segment
      (Co1) using glass microelectrodes. Stable recordings were obtained from 150 tail
      motoneurons. Stimulation of group-1 muscle afferents (stimulus intensity <1.8 T)
      often produced EPSPs (82/150) after stimulating nerves innervating neighboring
      tail muscles. Motoneurons innervating the long-tendoned muscles, M. extensor
      caudae lateralis and M. flexor caudae longus (ECL and FCL), received heteronymous
      monosynaptic connections from group-I muscle afferents innervating the
      ipsilateral tail muscles. The motoneurons innervating segmental muscles, M.
      extensor caudae medialis and M. flexor caudae brevis (ECM and FCB), received
      heteronymous monosynaptic connections from group-I muscle afferents innervating
      tail muscles on both sides. The motoneurons innervating tail muscles originated
      from the Ossa coxae, M. abductor caudae externus and M. abductor caudae internus
      (ACE and ACI), received monosynaptic connection from group-I muscle afferents
      innervating most of the tail muscles on both sides. Crossed disynaptic inhibitory
      pathways activated by primary muscle afferent inputs were observed in ECM, ACE,
      FCL, and FCB motoneurons. The effects of group-II afferent inputs were not
      dependent on the kind of motoneuron, and alternative excitatory and inhibitory
      pathways were not clearly observed in the tail motoneuron pool. It is suggested
      that variability of the neuronal pathways from group-I and -II muscle afferents
      to tail motoneurons corresponds to functional relationships among tail muscles,
      depending on the tail movements.

PMID- 10204767
TI  - Comparison of variability of initial kinematics and endpoints of reaching
      movements.
AB  - The accuracy of reaching movements to memorized visual target locations is
      presumed to be determined largely by central planning processes before movement
      onset. If so, then the initial kinematics of a pointing movement should predict
      its endpoint. Our study examined this hypothesis by testing the correlation
      between peak acceleration, peak velocity, and movement amplitude and the
      correspondence between the respective spatial positions of these kinematic
      landmarks. Subjects made planar horizontal reaching movements to targets located
      at five different distances and along five radially arrayed directions without
      visual feedback during the movements. The spatial dispersion of the positions of
      peak acceleration, peak velocity, and endpoint all tended to form ellipses
      oriented along the movement trajectory. However, whereas the peaks of
      acceleration and velocity scaled strongly with movement amplitude for all of the
      movements made at the five target distances in any one direction, the
      correlations with movement amplitude were more modest for trajectories aimed at
      each target separately. Furthermore, the spatial variability in direction and
      extent of the distribution of positions of peak acceleration and peak velocity
      did not scale differently with target distance, whereas they did for endpoint
      distributions. Therefore, certain features of the final kinematics are evident in
      the early kinematics of the movements as predicted by the hypothesis that they
      reflect planning processes. However, endpoint distributions were not completely
      predetermined by the Initial kinematics. In contrast, multivariate analysis
      suggests that adjustments to movement duration help compensate for the
      variability of the initial kinematics to achieve desired movement amplitude.
      These compensatory adjustments do not contradict the general conclusion that the
      systematic patterns in the spatial variability observed in this study reflect
      planning processes. On the contrary, and consistent with that conclusion, our
      results provide further evidence that direction and extent of reaching movements
      are planned and determined in parallel over time.

PMID- 10204768
TI  - Feedforward versus feedback control in children and adults subjected to a
      postural disturbance.
AB  - Any action performed by standing subjects is generally accompanied by
      compensatory postural activities, which reduce or abolish the postural
      disturbance generated by the movements and keep the subjects' center of gravity
      within the supporting base. These postural activities are triggered by either
      anticipatory and/or feedback-based control processes, depending on the
      information available and on the behavioral context. To investigate the
      respective involvement of these two components in postural control during
      development, we studied the extent to which the postural equilibrium of children
      (3-to 10-year-olds) and adults was disturbed by the same physical event, an
      unloading, depending on whether it was initiated by the subject or externally
      imposed. The subjects were standing on a force platform with their eyes closed,
      holding a load (5% of their own body weight) in their hands, with arms vertical
      and forearms horizontal. Two conditions were applied: (1) the subjects
      voluntarily released the load and (2) the load was unpredictably removed. The
      unloading resulted in a backward movement of the center of pressure, which was
      smaller with self-initiated than imposed disturbances in all age groups. This
      difference varied depending mainly on the age-related changes in the relative
      amplitude of the self-initiated disturbance, which decreased between 3- to 5-,
      and 6- to 8-year-olds (who showed no marked postural instability after self
      initiated unloading), and increased again in the two older groups (9- to 10-year
      olds and adults), in which it also became more consistent It was concluded that
      feedforward control. becomes more efficient as children grow up, but that its
      relative contribution to postural control does not show a monotonic pattern of
      development.

PMID- 10204769
TI  - A photothrombotic ring stroke model in rats with sustained hypoperfusion followed
      by late spontaneous reperfusion in the region at risk.
AB  - In clinical thromboembolic stroke, spontaneous late recanalization is a common
      feature, but one which has been very sparsely studied experimentally. This study
      aimed at enabling the study of spontaneous reperfusion and exploring its
      consequences by modifying a recently developed photothrombotic-stroke model that
      focuses on the region-at-risk located within an ischemic ring-locus. The exposed
      crania of male Wistar rats (280-340 g) were subjected to a ring-shaped (5.0 mm
      outer diameter and 0.35 mm thick) laser-irradiation beam (514.5 nm; 0.89 W/cm2)
      for 2 min simultaneously with intravenous erythrosin B (17 mg/kg) infusion for 30
      s. Transcardial carbon-black perfusion experiments revealed a ring-shaped
      cortical perfusion deficit at 4 h post-irradiation, which progressively increased
      at 10, 24, and 48 h, at which time the whole region-at-risk was pale with single
      distal branches of the middle cerebral artery being extensively narrowed, but not
      occluded. At 72 h, spontaneous reperfusion was observed in the region-at risk,
      which was even more pronounced at 7 and 28 days. Cortical cerebral blood flow
      (cCBF), measured by laser-Doppler flowmetry, was distinctly reduced at 2 min post
      irradiation and further decreased slightly during 4 h of recording to ca. 24% of
      baseline values at the ring locus and 40% in the region-at-risk. In the region-at
      risk, cCBF flow values were 23-30% of the baseline at 2448 h post-irradiation,
      followed by a relative cCBF increase to 71 and 77% at 72 and 96 h post
      irradiation. Brain water content in the ischemic part of the cortex increased
      steadily from 4 to 48 h post-irradiation; at 72 h, it leveled off and returned to
      control values at 7 days. In conclusion, by employing a laser beam in the shape
      of a thin ring, critically sustained cCBF reduction was followed by late,
      consistent spontaneous reperfusion in the region-at-risk in this novel
      photochemically induced stroke-in-evolution model.

PMID- 10204770
TI  - A photothrombotic ring stroke model in rats with remarkable morphological tissue
      recovery in the region at risk.
AB  - The photothrombotic ring stroke model with sustained underperfusion followed by
      late spontaneous reperfusion (Gu et al. 1999) was employed to study its
      morphological consequences. The exposed crania of adult male Wistar rats were
      subjected to a ring-shaped laser irradiation beam simultaneously with intravenous
      erythrosin B infusion. The ischemic volume was calculated from serial sections
      throughout the ischemic lesions at 4, 10, 24, 48, and 72 h and 7 days and 28 days
      after irradiation. The ischemic volume, expressed as a percentage of the
      ipsilateral hemispheric volume, increased steadily from 4 to 10 to 24 h to reach
      its maximum value at 48 h after irradiation; at 3 days, 7 days, and 28 days, the
      ischemic volume was reduced to 75%, 24%, and 22% of the value at 48 h. Evaluation
      of ischemic volumes at different anteroposterior levels revealed that the reduced
      ischemic volume at 72 h and later was mainly due to morphological restoration in
      the centrally located, nonirradiated region at risk. An initial enlargement and
      development of cystic coagulation necrosis was observed in the cortical areas
      corresponding to the ring lesion itself. In the region at risk, a gradually
      deteriorating neuropil and nerve cell morphology were observed over time, with
      maximum severity at 48 h postirradiation. At this time, most laminae II and III
      neurons in the region at risk exhibited eosinophilia and pyknosis but no
      incrustations, with small islands of less damaged neurons randomly scattered. At
      72 h and up to 28 days after irradiation, these cell characteristics were no
      longer observed and the region at risk was well populated with neurons that had a
      chiefly unremarkable cytological appearance. Neuronal counts in the central part
      of the region at risk were performed; no significant difference in neuronal
      density was observed between sham-operated controls and at 28 days after
      irradiation. In conclusion, the consistent, late spontaneous reperfusion
      coincided with remarkable tissue recovery as assessed morphologically in the
      region at risk. The data suggest that nerve cell repair may occur even after the
      detection, by conventional morphological methods, of prolonged critical ischemic
      neuronal damage in the setting of acute ischemic stroke.

PMID- 10204771
TI  - Activity-dependent development of cortical axon terminations in the spinal cord
      and brain stem.
AB  - Corticospinal (CS) axon terminations in several species are widespread early in
      development but are subsequently refined into a spatially more restricted
      distribution. We studied the role of neural activity in sensorimotor cortex in
      shaping postnatal development of CS terminations in cats. We continuously infused
      muscimol unilaterally into sensorimotor cortex to silence neurons during the
      postnatal CS refinement period (weeks 3-7). Using anterograde transport of WGA
      HRP, we examined the laterality of terminations from the muscimol-infused (i.e.,
      silenced) and active sides in the spinal cord, as well as in the cuneate nucleus
      and red nucleus. We found that CS terminations from the muscimol-infused cortex
      were very sparse and limited to the contralateral side, while those from the
      active cortex maintained an immature bilateral topography. Controls (saline
      infusion, noninfusion) had dense, predominantly contralateral, CS terminations.
      There was a substantial decrease in the spinal gray matter area occupied by
      terminations from the side receiving the blockade and a concomitant increase in
      the area occupied by ipsilateral terminations from the active cortex. Optical
      density measurements of HRP reaction product from the active cortex in muscimol
      infused animals showed substantial increases over controls in the ratio of
      ipsilateral to contralateral CS terminations for all laminae examined (IV-V, VI,
      VII). Our findings suggest that ipsilateral dorsal horn terminations reflect new
      axon growth during the refinement period because they are not present there
      earlier in development. Those in the ventral horn are present earlier in
      development and thus could reflect maintenance of transient terminations.
      Increased ipsilateral terminations from active cortex were due to recrossing of
      CS axons in lamina X and not to an increase in labeled CS axons in the
      ipsilateral white matter. Examination of brain stem terminations suggested that,
      between postnatal weeks 3 and 7, development of corticocuneate terminations also
      is activity-dependent but that development of corticorubral terminations is not.
      Activity-dependent CS development is a plausible mechanism by which early motor
      experiences could shape the anatomical and functional organization of the motor
      systems during a critical postnatal period.

PMID- 10204772
TI  - Pointing in 3D space to remembered targets. II. Effects of movement speed toward
      kinesthetically defined targets.
AB  - The accuracy of visually guided pointing movements decreases with speed. We have
      shown that for movements to a visually defined remembered target, the variability
      of the final arm endpoint position does not depend on movement speed. We put
      forward a hypothesis that this observation can be explained by suggesting that
      movements directed at remembered targets are produced without ongoing
      corrections. In the present study, this hypothesis was tested for pointing
      movements in 3D space to kinesthetically defined remembered targets. Passive
      versus active acquisition of kinesthetic information was contrasted. Pointing
      errors, movement kinematics, and joint-angle coordination were analyzed. The
      movements were performed at a slow speed (average peak tangential velocity of
      about 1.2 m/s) and at a fast speed (2.7 m/s). No visual feedback was allowed
      during the target presentation or the movement. Variability in the final position
      of the arm endpoint did not increase with speed in either the active or the
      passive condition. Variability in the final values of the arm-orientation angles
      determining the position of the forearm and of the upper arm in space was also
      speed invariant. This invariance occurred despite the fact that angular
      velocities increased by a factor of two for all the angles involved. The speed
      invariant variability supports the hypothesis that there is an absence of ongoing
      corrections for movements to remembered targets: in the case of a slower
      movement, where there is more time for movement correction, the final arm
      endpoint variability did not decrease. In contrast to variability in the final
      endpoint position, the variability in the peak tangential acceleration increased
      significantly with movement speed. This may imply that the nervous system adopts
      one of two strategies: either the final endpoint position is not encoded in terms
      of muscle torques or there is a special on-line mechanism that adjusts movement
      deceleration according to the muscle-torque variability at the initial stage of
      the movement. The final endpoint position was on average farther from the
      shoulder than the target. Constant radial-distance errors were speed dependent in
      both the active and the passive conditions. In the fast speed conditions, the
      radial distance overshoots of the targets increased. This increase in radial
      distance overshoot with movement speed can be explained by the hypothesis that
      the final arm position is not predetermined in these experimental conditions, but
      is defined during the movement by a feedforward or feedback mechanism with an
      internal delay.

PMID- 10204773
TI  - Olivofloccular circuit in oculomotor control: binocular optokinetic stimulation.
AB  - The metabolic activation of the olivocerebellar pathway during binocular
      optokinetic stimulation was studied in the guinea pig, by means of the
      semiquantitative 14C-2-deoxyglucose (2DG) technique. The experimental group
      underwent binocular horizontal stimulation, whereas the control animals were
      either kept in the dark or allowed to view a stationary pattern. The local
      metabolic activity index in the dorsal cap of the inferior olive was higher on
      the side contralateral to the eye that had been stimulated in the temporonasal (T
      N) direction in the horizontal group; in contrast, the floccular region showed
      higher activity on the side ipsilateral to the T-N-stimulated eye. These findings
      support the involvement of the olivocerebellar pathway in the horizontal
      optokinetic response. A phylogenetic hypothesis is suggested to explain
      inconsistent results found in the literature.

PMID- 10204774
TI  - Prevention of both T2- and diffusion-weighted increases in image intensity during
      cerebral hypoxia-ischemia in infant rats pretreated with dexamethasone.
AB  - The present study examines the effect of dexamethasone treatment on the intensity
      of changes in T2-weighted and diffusion-weighted (DW) magnetic resonance images
      occurring in infant rats during and after cerebral hypoxia-ischemia. The right
      carotid artery was occluded under isoflurane anesthesia in 7-day-old rats and
      images were acquired in sedated animals using a Bruker 9.4 T magnetic resonance
      (MR) system. Imaging changes were markedly different in rats pretreated with
      dexamethasone phosphate (0.1 mg/kg, i.p.) 24 h before hypoxia than in controls.
      In control animals, areas of hyperintensity ipsilateral to the occlusion occurred
      during hypoxia-ischemia in both the DW- and T2-weighted images with some recovery
      of the changes in early posthypoxia. In contrast, in dexamethasone-treated
      animals, areas of increased hyperintensity in the MR images did not occur. Thus,
      dexamethasone treatment prevents MR imaging changes during ischemia, suggesting
      that the cytotoxic edema associated with energy depletion and/or ionic
      disturbances during ischemia are also prevented by dexamethasone treatment.

PMID- 10204775
TI  - The variations of neuralgic amyotrophy.

PMID- 10204776
TI  - Neuralgic amyotrophy with phrenic nerve involvement.
AB  - Phrenic nerve involvement is a rare feature in patients with neuralgic amyotrophy
      (Parsonage-Turner syndrome). We report four patients who initially presented with
      severe dyspnea in the absence of lung disease. All patients had a history of
      infectious disease or surgery and of pain of sudden onset in the shoulder region.
      Weakness of the proximal arm was observed in only one. Radiographic and pulmonary
      function studies, phrenic nerve conduction studies, and needle electromyogram
      (EMG) of the diaphragm documented diaphragmatic paralysis which was unilateral in
      one patient, bilateral in two patients, and recurrent on alternating sides in
      another one. Follow-up studies remained abnormal for up to 4 years. Neuralgic
      amyotrophy with phrenic nerve involvement should be considered in patients
      presenting with severe, unexplained dyspnea of sudden onset.

PMID- 10204777
TI  - Blink reflex induced by controlled, ballistic mechanical impacts.
AB  - The blink reflex was induced by a defined mechanical impact covering the range
      from light touch to a hard, painful stroke, and by an electrical current. In both
      modes of stimulation, the R3--but not the R2--thresholds were correlated with
      subjective pain thresholds, suggesting a connection between R3 and nociceptor
      activation. However, R3 magnitude did not increase systematically with increasing
      levels of subjectively felt pain. The R3, induced by painful impacts, habituated
      quickly and was strongly affected by attention. The functional significance of
      the R3 component is discussed.

PMID- 10204778
TI  - Increase in the degree of coexpression of myosin heavy chain isoforms in skeletal
      muscle fibers of the very old.
AB  - Myosin heavy chain (MHC) isoform composition was determined in 2264 single
      skeletal muscle fibers from vastus lateralis muscle of a group (n = 12) of very
      old subjects (average age, 88 years). The number of fibers containing only MHC I,
      IIA, or IIX was 19.9%, 27.2%, and 0.3%, respectively. Surprisingly, 28.5% of the
      fibers displayed coexpression of both MHC I and IIA, a phenotype that is present
      in younger adults in very small percentages. Among these fibers coexpressing MHC
      I and IIA, the majority had a dominant expression of MHC I. Additionally, a small
      number of fibers coexpressing MHC I and IIX without any MHC IIA, and fibers co
      expressing all three isoforms were observed. Altogether, 52.6% of all fibers
      examined in these very old subjects coexpressed two or three MHC isoforms. The
      present study provides evidence that advanced age leads to a significant
      elevation of skeletal muscle fibers displaying coexpression of two MHC isoforms
      and that a separation into slow and fast fibers in very old individuals may
      therefore be somewhat misleading. The clinical significance of the elevated
      number of fibers coexpressing MHC I and IIA is uncertain.

PMID- 10204779
TI  - A new technique for recording sensory conduction velocity of the inferior
      alveolar nerve.
AB  - A new electrophysiological technique for recording the sensory conduction
      velocity (SNCV) of the inferior alveolar nerve (IAN) is described. Bilateral
      orthodromic recordings were done in 21 healthy adults. The sensory responses of
      the IAN were obtained in all 42 nerves examined with silver wire or monopolar
      needle electrodes inserted beneath the zygomatic arc in front of the
      temporomandibular joint to a depth of 4-4.5 cm, near the oval foramen. A small
      bipolar surface electrode was used for stimulation at the mental foramen. In 3
      subjects, the stimuli were additionally delivered via two monopolar needle
      electrodes to reduce the stimulus artifact. Single responses were usually
      sufficient for analysis, but, in some cases, averaging was adopted to improve the
      signal-to-noise ratio. Response latencies and amplitudes, SNCVs, and interside
      differences were measured, and the 97.5% upper and 2.5% lower prediction limits
      calculated for reference limits in clinical practice. This new technique provides
      a sensitive and objective diagnostic tool for the examination of IAN injuries,
      and may also be used for intraoperative monitoring of the IAN during mandibular
      surgery.

PMID- 10204780
TI  - Elucidation of muscle-binding peptides by phage display screening.
AB  - Muscle makes up the largest tissue volume of the body, yet its size makes muscle
      specific therapy difficult. This becomes particularly relevant when approaches to
      gene therapy for inherited myopathies are evaluated. Thus, a mechanism to target
      constructs or pharmaceuticals to muscle following intravenous injection would be
      advantageous. By screening a random phage display library we have identified a
      heptapeptide sequence, ASSLNIA, with enhanced in vivo skeletal and cardiac muscle
      binding. Phage carrying this peptide showed a 9- to 20-fold (depending on control
      tissue) increase in muscle selectivity compared with phage with no insert. When
      the injected individual phage clone was localized by immunohistochemistry, it was
      found within focal areas of the membrane of myofibers. Thus, the peptide
      identified represents a ligand that is capable of accessing skeletal and cardiac
      muscle from the lumen of blood vessels and could therefore readily be exploited
      for targeted delivery to muscle cells.

PMID- 10204781
TI  - The cutaneous silent period is mediated by spinal inhibitory reflex.
AB  - High-intensity cutaneous stimuli inhibit tonically firing motor neurons resulting
      in a silent period (CSP) in EMG activity. To determine the central nervous system
      (CNS) circuitry of this inhibitory reflex, soleus H reflexes evoked by tibial
      nerve stimuli were conditioned by high-intensity sural stimuli in 5 normal men
      and 5 men with complete, traumatic cervical myelopathy. The sural-tibial
      interstimulus interval (ISI) was varied between 0 and 200 ms. In normals, the CSP
      in the tonically contracted soleus muscle began 90-100 ms after sural stimuli and
      had a duration of 60-80 ms. In the relaxed soleus, the conditioned soleus H
      reflex amplitude was correspondingly reduced at ISIs of 60-120 ms. In patients,
      conditioned H-reflex amplitude was also reduced over the same ISI range, but the
      degree of inhibition was significantly less than in normals. These data support
      the hypothesis that the CSP is mediated by a spinal inhibitory reflex that is
      subject to supraspinal descending control.

PMID- 10204782
TI  - Heart involvement in muscular dystrophies due to sarcoglycan gene mutations.
AB  - Mutations in the sarcoglycan genes cause autosomal-recessive muscular
      dystrophies. Because sarcoglycan genes and their protein products are highly
      expressed both in skeletal and cardiac muscle, patients with these mutations
      might be expected to be at risk to develop dilated cardiomyopathy. We therefore
      studied 13 patients with alpha-, beta-, gamma-sarcoglycan gene mutations by
      thorough cardiological assessment. Electrocardiographic or echocardiographic
      abnormalities were observed in about 30% of cases showing a severe course of
      muscular dystrophy. No correlation was found between the presence of cardiac
      abnormalities and the type of mutation or sarcoglycan gene involved. The cardiac
      involvement was never severe, but it may be detected in early stages of the
      muscle disease. The absence of overt cardiac dysfunction may be due to lower
      sarcoglycan protein expression in cardiac than skeletal muscle or to less
      sarcolemmal instability at the myocardial level, possibly related to the
      different distribution of forces generated by contraction of the myocardium with
      respect to proximal limb-girdle muscles.

PMID- 10204783
TI  - Quantitative electrophysiologic studies in sporadic inclusion body myositis.
AB  - Sporadic inclusion body myositis (S-IBM) is a progressive, acquired disease of
      unknown etiology. Prior studies have suggested neurogenic involvement based on
      electrophysiologic data, although the biopsy is compatible with a myopathic
      process. Quantitative electrophysiologic studies were performed in the biceps
      brachii of 17 subjects with biopsy-proven S-IBM. Quantitative motor unit action
      potential (MUAP) analysis was compatible with myopathy in 16 subjects, with the
      remaining subject being within normal limits. Quantitative interference pattern
      was myopathic in all 13 subjects studied. Macro-EMG MUAP amplitude was reduced in
      3 of 17 studies; the remainder were within normal range, and none was increased
      as would be expected in neurogenic disease. Fiber density was normal to
      borderline increased in all subjects. Possible reasons for encountering
      neurogenic-appearing MUAPs may include choice of muscle studies, because some
      patients have co-existing polyneuropathy and large-amplitude MUAPs from
      hypertrophied muscle fibers. The data from this study indicate that S-IBM is a
      myopathic process.

PMID- 10204784
TI  - M-wave changes after high- and low-frequency electrically induced fatigue in
      different muscles.
AB  - The mechanisms of fatigue-induced changes in evoked compound muscle action
      potential (M-waves) are not well documented. In rats, isolated fast-glycolytic
      (tibialis anterior, or TA) and slow-oxidative muscles (soleus, or SOL) were
      stimulated repetitively at a low (10-Hz) or high (80-Hz) rate. Decreased
      amplitude and prolonged duration of M-waves were only significant after high
      frequency fatigue in TA and SOL muscles; that is, in the conditions in which an
      influx of calcium was measured. On the other hand, maximal force failure and
      maximal lactic acid increase in the bath medium occurred in TA muscle after high-
      and low-frequency fatigue trials. Postfatigue increase in potassium concentration
      occurred in all circumstances. Thus, M-wave alterations depend mainly on the
      stimulation paradigm and not on the muscle type, and cannot be used as a marker
      of changes in intracellular potassium or lactate ions. This amplifies
      understanding of the significance of M-wave changes in human exercise protocols.

PMID- 10204785
TI  - Relationships between clinical symptom severity scales and nerve conduction
      measures in carpal tunnel syndrome.
AB  - This study examined the severity of symptoms in carpal tunnel syndrome (CTS) in
      relation to nerve conduction measures of the median nerve. Clinical symptom
      severity and nerve conduction studies were evaluated for 64 hands with CTS in 45
      patients. We found the following: (1) significant relationships identified among
      the clinical scales resulted in a dichotomous symptom classification scheme into
      primary and secondary symptoms, with the former being more specific for those
      symptoms usually seen in association with nerve injury; (2) there were
      significant relationships between symptom severity and nerve conduction
      abnormality; (3) the primary symptom scale correlated more strongly with the
      electrodiagnostic measures of nerve injury than did the secondary symptom scale.
      Based on these findings, we believe that these clinical scales have biological
      significance and reflect median nerve injury. This would support their potential
      utility for evaluating the outcome of CTS treatment and developing a model for
      exposure-severity relationship.

PMID- 10204786
TI  - Changes in expression of voltage-gated potassium channels in dorsal root ganglion
      neurons following axotomy.
AB  - Several families of voltage-gated potassium channels (Kv), including a spectrum
      of subtypes, are involved in regulating and modifying the integration and
      transmission of electrical signals in the nervous system. However, the specific
      patterns of Kv expression in normal or injured dorsal root ganglion (DRG) neurons
      have not been studied. Previous studies have examined the expression of voltage
      gated sodium channels in DRG neurons, and also the selective up- and
      downregulation of several of these channels following axonal injury to the DRG
      neurons. In the present study, we used immunocytochemical methods to investigate
      the expression of Kv channels (Kv1.1, 1.2, 1.3, 1.4, 1.5, 1.6, and 2.1) in DRG
      cells cultured from control and axotomized adult rats. Kv1.2 and 2.1
      immunoreactivity in DRG neurons showed large decreases following axotomy, whereas
      Kv1.1 and 1.3 showed smaller decreases. Kv1.4 and 1.6 immunostaining were not
      altered by axotomy, and Kv1.5 immunoreactivity was low in both control and
      axotomized DRG neurons. These results provide molecular correlates for the
      expression of multiple K+ currents in normal DRG neurons and indicate that, in
      relation to changes in sodium channel expression, there are decreases in specific
      potassium channels following axotomy in these cells. The alterations in K+ and
      Na+ channel expression following axonal injury may lead to changes in electrical
      excitability of the DRG neurons, and might contribute to chronic pain syndromes.

PMID- 10204787
TI  - Assessment of trigeminal small-fiber function: brain and reflex responses evoked
      by CO2-laser stimulation.
AB  - Laser pulses selectively excite mechano-thermal nociceptors and evoke brain
      potentials that may reveal small-fiber dysfunction. We applied CO2-laser pulses
      to the perioral and supraorbital regions and recorded the scalp laser-evoked
      potentials (LEPs) and reflex responses in the orbicularis oculi, masticatory, and
      neck muscles in 30 controls and 10 patients with facial sensory disturbances. Low
      intensity pulses readily evoked scalp potentials consisting of a negative
      component with a latency of 165 ms followed by a positive component at 250 ms. In
      vertex recordings, the amplitude of LEPs exceeded 30 microV. Although only high
      intensity pulses evoked reflex responses, some subjects showed--even to low
      intensity pulses--an orbicularis oculi (blink-like) response that markedly
      contaminated the scalp recording. Scalp LEPs were abnormal in patients with
      hypalgesia and normal trigeminal reflexes and normal in patients with normal pain
      sensitivity and abnormal trigeminal reflexes. Possibly because of the high
      receptor density in this area and the short conduction distance, laser
      stimulation of the trigeminal territory yields low-threshold and large LEPs,
      which are useful for detecting dysfunction in peripheral and central pain
      pathways.

PMID- 10204788
TI  - Dystrophin and utrophin do not play crucial roles in nonmuscle tissues in mice.
AB  - The loss of full-length dystrophin from skeletal muscle leads to the clinical
      features of Duchenne muscular dystrophy. Both Dp71, a C-terminal dystrophin
      isoform, and the dystrophin-related protein, utrophin, are present at high levels
      in many nonmuscle tissues. To investigate the roles of these proteins in
      nonmuscle tissues, mice were generated null for utrophin, and deficient in all
      dystrophin isoforms. These mice reach adulthood and do not appear to have any
      devastating pathology in nonmuscle tissues.

PMID- 10204789
TI  - Reduction of motor artifact in antidromic ulnar sensory studies.
AB  - Motor artifact often interferes with recording of antidromic ulnar sensory
      responses from digit 5. In the belief that this artifact is due to a volume
      conducted motor response, eight different recording electrode and finger
      positions were evaluated in 10 normal subjects in an attempt to reduce or
      eliminate it. Placement of the recording electrodes over the middle and distal
      phalanges of digit 5 while the fingers were extended and abducted reduced this
      artifact most effectively, with minimal decrease in amplitude of the sensory
      response. This finding has important implications for the routine performance of
      antidromic sensory conduction studies of the ulnar nerve.

PMID- 10204790
TI  - Technology review: the Neurometer Current Perception Threshold (CPT). AAEM
      Equipment and Computer Committee. American Association of Electrodiagnostic
      Medicine.

PMID- 10204791
TI  - Conduction block and continuous motor unit activity in chronic acquired
      demyelinating polyneuropathy.
AB  - The term continuous motor unit activity (CMUA) may be used to refer to the
      involuntary, sustained activity of motor units caused by hyperactivity of
      peripheral motor nerves. CMUA has been reported in association with acquired
      neuropathies such as chronic inflammatory demyelinating polyneuropathy. The
      precise mechanism responsible for the excess muscle activity is not defined, but
      the activity is believed to originate in the peripheral nerves, perhaps at sites
      of focal demyelination. We describe a case of an acquired, demyelinating
      neuropathy associated with distal motor conduction block in which CMUA was
      observed in muscles innervated by blocked axons. Despite the prolonged disease
      duration of nearly 40 years, marked clinical and electrophysiological improvement
      as well as resolution of the CMUA were observed following immunosuppressive
      therapy. A relationship between the chronic motor conduction block and the excess
      muscle activity is postulated.

PMID- 10204792
TI  - Reproducibility of corticomotor threshold: some observations.

PMID- 10204793
TI  - Shounousui and the blink reflex.

PMID- 10204794
TI  - A new technique for proving needle placement in the muscles of cadavers.

PMID- 10204795
TI  - Rigid spine syndrome with fiber type disproportion.

PMID- 10204796
TI  - Serum immunoglobulin A deficiency in relapsing inflammatory demyelinating
      polyneuropathy.

PMID- 10204797
TI  - Severe hypokalemic myopathy in Gitelman's syndrome.

PMID- 10204798
TI  - Fascicular constriction in the anterior interosseous nerve and other motor
      branches of the median nerve.

PMID- 10204799
TI  - Microarrays and toxicology: the advent of toxicogenomics.
AB  - The availability of genome-scale DNA sequence information and reagents has
      radically altered life-science research. This revolution has led to the
      development of a new scientific subdiscipline derived from a combination of the
      fields of toxicology and genomics. This subdiscipline, termed toxicogenomics, is
      concerned with the identification of potential human and environmental toxicants,
      and their putative mechanisms of action, through the use of genomics resources.
      One such resource is DNA microarrays or "chips," which allow the monitoring of
      the expression levels of thousands of genes simultaneously. Here we propose a
      general method by which gene expression, as measured by cDNA microarrays, can be
      used as a highly sensitive and informative marker for toxicity. Our purpose is to
      acquaint the reader with the development and current state of microarray
      technology and to present our view of the usefulness of microarrays to the field
      of toxicology.

PMID- 10204800
TI  - Mechanistic studies of the effects of the retinoid N-(4-hydroxyphenyl)retinamide
      on prostate cancer cell growth and apoptosis.
AB  - To explore the mechanisms underlying the chemopreventive effects of the synthetic
      retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) in prostate cancer, we evaluated
      the anti-proliferative and apoptosis-inducing effects of 4-HPR in the androgen
      sensitive human prostate cancer cell line LNCaP. 4-HPR decreased the number of
      viable LNCaP cells (as measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay) in a dose-dependent manner. Although 4-HPR
      exerted a modest G1 cell-cycle block (as determined by flow cytometry), its
      effect on reduced cell number appeared to result primarily from induction of
      apoptosis (as measured by an enzyme-linked immunosorbent assay and flow
      cytometric assays). The mitogenic effects of R1881, a non-metabolizable androgen
      that potently induces LNCaP cell proliferation, was completely blocked by greater
      than 0.5 microM 4-HPR. Furthermore, increasing the R1881 concentration in the
      presence of 2.0 microM 4-HPR increased apoptotic cell death. 4-HPR decreased
      prostate-specific antigen (PSA) protein levels in conditioned medium and
      decreased PSA mRNA expression. 4-HPR also decreased the ratio of bcl-2 to bax
      mRNA expression in LNCaP cells by approximately 45%, indicating that the
      apoptotic effects of 4-HPR may be mediated, at least in part, by alterations in
      the bcl-2/bax-regulated apoptotic pathway. N-acetylcysteine (4 mM) completely
      blocked the anti-proliferative and apoptotic-inducing effects of 4-HPR,
      suggesting that an oxidative mechanism may be involved. We concluded that (i) 4
      HPR exerts growth-suppressive and apoptotic effects on LNCaP cells, (ii) 4-HPR
      can interact with androgen to suppress proliferation and induce apoptosis, (iii)
      the apoptotic effects of 4-HPR may be mediated in part by the bcl-2/bax pathway,
      and (iv) a pro-oxidant mechanism may contribute to the anti-proliferative and
      apoptotic-inducing effects of 4-HPR.

PMID- 10204801
TI  - Prevention of DNA photodamage by vitamin E compounds and sunscreens: roles of
      ultraviolet absorbance and cellular uptake.
AB  - Topical application of alpha-tocopherol (alphaTH), the most prominent naturally
      occurring form of vitamin E, inhibits ultraviolet (UV) B-induced
      photocarcinogenesis and DNA photodamage in C3H mice in vivo. In this study, we
      compared alphaTH with other vitamin E compounds and with three commercial
      sunscreen compounds for their ability to inhibit DNA photodamage in C3H mouse
      skin in vivo. When applied in a 5% dispersion in a neutral cream vehicle, alpha
      tocopherol (alphaTH), gamma-tocopherol (gammaTH), and delta-tocopherol (deltaTH)
      each produced a statistically significant inhibition of thymine dimer formation,
      whereas alpha-tocopherol acetate (alphaTAc) and alpha-tocopherol methyl ether
      (alphaTOMe) did not. Application of 5% dispersions of the commercial sunscreen
      agent octylmethoxycinnamate also inhibited dimer formation, whereas ethylhexyl
      salicylate and oxybenzone did not, despite their considerably greater UVB
      absorbances than alphaTH. To test the hypothesis that cellular uptake and
      distribution are necessary for optimal photoprotection by tocopherols,
      photoprotection was studied in mouse 308 keratinocyte cells in vitro.
      Preincubation of 308 cells with 1 microM alphaTH for at least 2 h before exposure
      to 2.5 J/m2/s UVB for 10 min significantly (P < 0.05) attenuated thymine dimer
      formation. Pre-incubation with 1 microM gammaTH, deltaTH, alphaTAc, or alphaTOMe
      for 2 h did not inhibit thymine dimer formation significantly. Uptake of alphaTH
      was measured after incubation with 1 microM [2H3]alphaTH (d3-alphaTH) and
      resulted in a time-dependent increase in alphaTH levels. Use of d3-alphaTH
      allowed separate, simultaneous measurement of added d3-alphaTH and unlabeled
      endogenous alphaTH by gas chromatography-mass spectrometry. Accumulation of 167
      +/- 62 pmol d3-alphaTH/mg protein was measured within 1 h in whole-cell
      fractions. d3-AlphaTH in the nuclear fraction reached levels of 15 +/- 4 pmol d3
      alphaTH/mg protein at 2 h. Accumulation of alphaTH in the whole cell and nuclei
      corresponded temporally with significant protection against DNA photodamage. The
      kinetics of accumulation of the three tocopherols in whole cells and in nuclei
      were similar. Although only alphaTH conferred significant protection compared
      with irradiated controls at 2 h, the differences between individual tocopherols
      were not statistically significant. This work suggests that incorporation of
      tocopherol compounds into sunscreen products confers protection against
      procarcinogenic DNA photodamage and that cellular uptake and distribution of
      tocopherol compounds is necessary for their optimal photoprotection.

PMID- 10204802
TI  - Differential expression of matrilysin and cyclooxygenase-2 in intestinal and
      colorectal neoplasms.
AB  - Both the matrix metalloproteinase matrilysin and the prostaglandin H synthase
      cyclooxygenase-2 (Cox-2), are thought to play key roles in colorectal
      carcinogenesis. These enzymes are overexpressed in 85-90% of human colorectal
      cancers. Furthermore, mice carrying an adenomatous polyposis coli germline
      mutation that are also nullizygous for either matrilysin or Cox-2 display a
      significant reduction in tumor multiplicity. To determine if there is a direct
      link between matrilysin and Cox-2, their expression was characterized in two
      mouse models of intestinal carcinogenesis and in human colorectal tumor samples.
      Both matrilysin and Cox-2 expression was increased in the mouse models and in the
      human colorectal cancers; however, immunohistochemistry and in situ hybridization
      indicated that their localization within the tumors was different. In the mouse
      models, Cox-2 was expressed in the superficial stroma, whereas matrilysin
      expression was localized exclusively to the neoplastic epithelium. In contrast,
      in human colorectal cancers, both Cox-2 and matrilysin were expressed in the
      neoplastic epithelium. Although over 80% of the specimens expressed both
      matrilysin and Cox-2, the levels and localization of matrilysin and Cox-2
      expression were distinct. Cox-2 expression was strongest in well-differentiated
      areas, and matrilysin immunostaining was strongest in the more dysplastic and
      invasive regions of the tumor. These results indicate that these two important
      modulators of colorectal tumorigenesis are differentially expressed and imply
      that the therapeutic benefit may be improved by combination therapy utilizing
      selective Cox-2 and matrilysin inhibitors.

PMID- 10204803
TI  - The regulation of ribonucleoside diphosphate reductase by the tumor promoter
      orotic acid in normal rat liver in vivo.
AB  - Our earlier studies have shown that in normal hepatocytes, orotic acid (OA)
      inhibits DNA synthesis induced by several growth factors in vitro and after two
      thirds partial hepatectomy (PH) in vivo. As in the normal liver OA induces an
      imbalance in nucleotide pools (specifically, an increase in uridine nucleotides,
      including deoxyuridine nucleotides, and a decrease in adenosine nucleotides,
      including ATP) and creation of this imbalance is crucial for the mitoinhibitory
      effects of OA, we hypothesized that ribonucleoside diphosphate reductase (RNR), a
      key enzyme in DNA synthesis that is regulated by nucleotide/deoxynucleotide
      levels, might be one of the targets for the inhibition of DNA synthesis by OA. To
      test this hypothesis, we subjected male Fischer 344 rats (130-150 g) to two
      thirds PH in the absence or in the presence of OA (a 300-mg tablet of OA methyl
      ester implanted intraperitoneally at the time of two-thirds PH). The rats were
      killed at different times later, and their livers were processed for analysis of
      levels of RNR enzyme activity, protein, and mRNA transcripts. The results
      obtained indicated that treatment with OA resulted in a near-100% inhibition of
      RNR induced by two-thirds PH in rat liver, as monitored by enzyme activity and
      protein level. Furthermore, this inhibition was paralleled by a decrease in the
      mRNA transcripts for both the M1 and M2 subunits of RNR. Nuclear run-off assays
      indicated that this decrease in the levels of mRNA transcripts could not be
      attributed to an effect on transcription. However, administration of OA 20 h
      after two-thirds PH, when RNR mRNA transcripts were maximally induced, resulted
      in increased degradation of the RNR M1 and M2 subunits. Taken together, these
      results indicate that OA treatment decreases RNR levels induced by two-thirds PH,
      at the levels of enzyme activity, protein, and mRNA transcripts, and the
      decreased levels of mRNA transcripts appeared to be due to increased degradation
      of the transcripts.

PMID- 10204804
TI  - Increased tumor cell proliferation in murine tumors with decreasing dosage of
      wild-type p53.
AB  - A number of transgenic animal model systems have addressed the mechanistic role
      of p53 loss in tumor progression. However, many of these tumor models have
      analyzed p53 function in the context of other transgenes expressing activated
      oncogenes or defective tumor suppressor genes generated by gene targeting. To
      examine the role of p53 loss independent of other exogenous oncogenic influences,
      we analyzed some of the biological aspects of tumor formation and progression in
      p53-knockout mice containing a null germline p53 allele. We analyzed tumors from
      p53-/-, p53+/-, and p53+/+ littermates. Some of the p53+/- tumors had lost the
      remaining p53 allele (p53+/- loss of heterozygosity), whereas others retained the
      allele (p53+/-). In this report, we show that loss or absence of p53 conferred a
      tumor growth advantage by increasing the rate of cellular proliferation in a p53
      dosage-dependent manner. The apoptotic levels in tumor tissue were found to be
      modest and not significantly dependent on p53 status. These results contrast with
      those from some other p53-deficient tumor models, in which p53 loss was
      associated with more rapid tumor progression through abrogated apoptosis.
      Finally, as p53 has been shown to regulate certain angiogenic factors, we
      examined the levels of angiogenesis in p53-containing and p53-deficient tumors.
      We found no p53-dependent differences in the levels of tumor angiogenesis
      measured by intratumoral microvessel density.

PMID- 10204805
TI  - Telomere shortening, telomerase expression, and chromosome instability in rat
      hepatic epithelial stem-like cells.
AB  - Telomeres, which are specialized structures consisting of T2AG3 repeats and
      proteins at the ends of chromosomes, may be essential for genomic stability. To
      test whether telomere length maintenance preserves genomic stability in rats
      (Rattus rattus and Fischer 344), we assayed telomerase activity and telomere
      length in the rat hepatic epithelial stem-like cell line WB-F344 during aging in
      vitro and in tumor-derived lines. Telomerase activity in the parental WB-F344
      line was repressed at low and intermediate passage levels in vitro and
      reexpressed at high passages. Southern blot hybridization and quantitative
      fluorescence in situ hybridization analyses demonstrated that telomeres were
      significantly eroded at intermediate passage levels, when telomerase was
      repressed, and at high passage levels, when telomerase was expressed.
      Fluorescence in situ hybridization analysis also revealed interstitial telomeric
      sequences in rat chromosomes. Tumor-derived WB-F344 cell lines that express
      telomerase had variably shortened telomeres. Cytogenetic analyses performed on WB
      F344 cells at low, intermediate, and high passages demonstrated that chromosome
      instability was most severe in the intermediate passage cells. These data suggest
      that telomere shortening during aging of rat hepatic epithelial stem-like WB-F344
      cells in vitro and during selection of tumorigenic lines in vivo may destabilize
      chromosomes. Expression of telomerase in high passage cells appeared to partially
      stabilize chromosomes.

PMID- 10204806
TI  - Expression of FHIT in primary cultures of human epithelial ovarian tumors and
      malignant ovarian ascites.
AB  - Abnormal FHIT gene expression has been reported in a variety of epithelial tumors
      shown to harbor deletions of chromosome 3p14, the chromosomal assignment of this
      gene. Recently, we described loss of heterozygosity of 3p in a subset of
      epithelial ovarian cancers. To investigate a potential role of the FHIT gene in
      ovarian cancer, we examined primary cell cultures derived from normal ovarian
      surface epithelium, ovarian tumors, and the cellular fraction of malignant
      ascites to determine the expression of FHIT by using reverse transcription
      polymerase chain reaction. Included in this analysis were four spontaneously
      immortalized cell lines: three derived from malignant epithelial ovarian tumors
      (TOV21G, TOV112D, and TOV81D) and one from malignant ovarian ascites (OV90). OV90
      was previously shown to harbor a deletion of the whole p arm of chromosome 3. The
      FHIT transcript was not detectable in two of 11 primary cultures derived from
      normal ovarian surface epithelium or in a primary culture derived from malignant
      ovarian ascites, whereas the remaining samples (34 malignant, eight borderline,
      and three benign specimens), exhibited identical expression patterns. In each
      case, this pattern was consistent with the co-expression of a normal FHIT
      transcript and a smaller transcript. DNA sequencing revealed that the abnormal
      sized message lacked exons 4-7 (inclusive), which were deleted at their exact
      intron-exon splice sites. The aberrant-sized transcript was detectable by
      Northern blot analysis. There was no concordance between FHIT expression and loss
      of heterozygosity at the FHIT locus. Northern blot analysis also revealed that
      FHIT was differentially expressed, and the spontaneously immortalized cell lines
      TOV21G and TOV112D showed the highest level of expression. Because the same
      reverse transcription-polymerase chain reaction expression pattern was observed
      in both normal and tumor-derived primary cell cultures, these results argue
      against a significant role for FHIT in epithelial ovarian tumorigenesis.

PMID- 10204807
TI  - Sjogren's syndrome: lymphoma predisposition coupled with a reduced frequency of
      t(14;18) translocations in blood lymphocytes.
AB  - Sjogren's syndrome (SS) is a systemic autoimmune disorder with a strong tumor
      predisposition (a 44-fold elevated incidence of non-Hodgkin's lymphoma has been
      reported). By polymerase chain reaction analysis of t(14;18), a key lymphomagenic
      event in peripheral blood lymphocytes, we found a lower frequency in a subset of
      12 SS patients positive for SS-A/SS-B autoantibodies than in 21 healthy subjects
      and 20 SS patients lacking these SS marker autoantibodies (P < 0.001). All 14
      mutants sequenced displayed signs typical of V(D)J recombinase activity. This
      perplexing result of a low rate of t(14;18) in a population strongly predisposed
      to t(14;18)-associated tumor development may be explained by a constitutive
      deficiency in V(D)J recombinase leading to autoimmunity and increased
      lymphoproliferation.

PMID- 10204808
TI  - Frequent mutations of the rat beta-catenin gene in colon cancers induced by
      methylazoxymethanol acetate plus 1-hydroxyanthraquinone.
AB  - Recent evidence suggests that the beta-catenin gene (CTNNB1) acts as an oncogene,
      and some human colon tumors with an intact APC gene have activating mutations in
      CTNNB1. In this study, mutations in the region corresponding to N-terminal
      phosphorylation sites (codons 1-51) of the rat Ctnnb1 gene were investigated in
      20 colon tumors associated with ulcerative colitis and induced with
      methylazoxymethanol acetate and 1-hydroxyanthraquinone. Ninety percent (18 of 20)
      of the tumors induced in male F344 rats harbored mutations, which were detected
      in three of four adenomas (75%) and 15 of 16 adenocarcinomas (94%). Of 18 total
      missense mutations, 13 (72%) were G-->A transitions at position 101, three were G
      ->A transitions at position 94, and two were C-->T transitions at position 122,
      resulting in the amino acid substitutions Gly34-->Glu, Asp32-->Asn, and Thr41-
      >Ile, respectively. Although there were no mutations in the Apc gene, as we
      previously reported in the same tumor samples, the results obtained in this study
      strongly implicate the Apc-beta-catenin-T-cell factor (Tcf) signaling pathway in
      methylazoxymethanol acetate, 1-hydroxyanthraquinone-induced colon carcinogenesis.

PMID- 10204809
TI  - Is serum uric acid a risk factor for coronary heart disease?
AB  - The role of uric acid as an independent risk factor in the development of
      coronary heart disease (CHD) has been questioned as serum urate is related to
      many of the established etiological risk factors for cardiovascular disease which
      could confound the observed association. This review assesses the role of
      elevated serum uric acid as an independent role for coronary heart disease.

PMID- 10204810
TI  - Dietary salt restriction in pregnancy an outmoded practice.

PMID- 10204811
TI  - Sodium-blood pressure interrelationship in pregnancy.
AB  - In non-pregnant individuals, a strong positive association of sodium intake with
      blood pressure has been established, but the relationship between sodium intake
      and blood pressure in human pregnancy remains obscure up to date. The aim of this
      prospective observational cohort study was to assess the relationship between
      urinary sodium excretion (as a measure for intake) and blood pressure from the
      early second trimester onwards throughout pregnancy. The study group consisted of
      667 low-risk women with singleton pregnancies, of whom 350 were nulliparous and
      317 parous. Blood pressure was measured in a standardised fashion at
      predetermined intervals from the first antenatal visit prior to 16 weeks
      gestation until delivery. Urinary sodium excretion was measured in 24-h urine
      collections on at least four occasions between 16 and 38 weeks gestation. Main
      outcome measures were the coefficients of correlation between changes in urinary
      sodium output and changes in blood pressure during six different gestational
      epochs. No significant correlations were found between changes in urinary sodium
      output and changes in blood pressure. Correlation coefficients were alike for
      nulliparous and parous women and for different gestational intervals. Prior to 32
      weeks gestation, no differences were observed in sodium excretion between women
      who remained normotensive and those who developed gestational hypertension. These
      results suggest that changes in sodium intake are not associated with blood
      pressure changes in low-risk pregnant women. Blood pressure increases as observed
      in the second half of normotensive and hypertensive pregnancies are unlikely to
      be caused by changes in renal sodium handling.

PMID- 10204813
TI  - Ambulatory blood pressure profiles in essential hypertensives after treatment
      with a new once daily nifedipine formulation.
AB  - The antihypertensive efficacy of a new controlled-release preparation of
      nifedipine developed for once daily administration was investigated in comparison
      with a standard therapy with sustained-release nifedipine given twice daily in a
      randomised, open crossover trial. Twenty-two patients with mild to moderate
      essential hypertension were enrolled. Ambulatory blood pressure monitoring (ABPM)
      was performed after a wash-out period and after a 3 weeks treatment with 40 mg
      controlled-release nifedipine once daily and 20 mg sustained-release nifedipine
      twice daily, respectively. ABPM data were evaluated by conventional linear
      analysis and by rhythm analysis. Both once daily and twice daily administration
      of nifedipine significantly reduced systolic blood pressure during the daytime
      and during the night when compared with baseline. The 24-h diastolic blood
      pressure was significantly decreased by both treatments, but only the once daily
      regimen significantly lowered both diastolic daytime and night-time means.
      Comparing systolic and diastolic blood pressures after both treatments, however,
      no significant differences were obtained. Both nifedipine treatments did neither
      greatly modify the circadian blood pressure pattern nor reflexly increase heart
      rate. In conclusion, once daily application of the controlled-release formulation
      of nifedipine resulted in a consistent and significant blood pressure reduction.
      Once daily and twice daily medications of nifedipine were about equally effective
      in lowering the elevated blood pressures.

PMID- 10204812
TI  - A new treatment of severe pre-eclampsia by long-term epidural anaesthesia.
AB  - We hypothesised that long term epidural anaesthesia suppresses sympathetic
      overactivity in pre-eclampsia. Two equal groups of severe pre-eclamptic patients
      were treated either with long-term epidural anaesthesia (epidural group) or bed
      rest, diet control, and an antihypertensive drug (control group). After 7 days of
      epidural block, mean arterial blood pressures decreased, platelet count and serum
      total protein increased in all cases while proteinuria decreased in four cases.
      All patients treated with a long-term epidural therapy continued their
      pregnancies for more than 3 weeks after admission. The infants in the epidural
      group had 1-min Apgar scores above 8, a body weight of 2240+/-310 g (mean +/-
      s.d.) and normal neonatal progress. In contrast, the pregnancies of eight
      patients in the control group were terminated within 2 weeks of admission due to
      severe pre-eclampsia or foetal distress, the birth weight of the infants was
      1590+/-380 g (mean +/- s.d.) and four had neonatal distress. Progressive
      worsening in the mean arterial pressure, proteinuria, platelet count and serum
      total protein was found in these patients. Long-term epidural anaesthesia
      suppresses the sympathetic hyperactivity and thus improves pre-eclamptic
      condition which may open a new treatment in case of progressive severe pre
      eclampsia.

PMID- 10204814
TI  - Baroreflex control of heart rate is impaired in pre-eclampsia.
AB  - Autonomic nervous dysfunction, such as parasympathetic and sympathetic
      impairment, has been suggested as possible cause of pre-eclampsia, but the
      studies are not conclusive. Our purpose was to assess non-invasively if pre
      eclampsia is associated with a decreased baroreflex function. Nine women with pre
      eclampsia (PE), eight normotensive pregnant women, and seven healthy normotensive
      non-pregnant women were studied. Continuous finger blood pressure was recorded by
      a Portapres device in the left lateral recumbent position and active standing.
      Baroreflex gain was evaluated by cross-spectral analysis of systolic blood
      pressure and pulse interval. The result was that baroreflex gain at rest was
      lower in pre-eclamptic women both compared to non-pregnant and healthy pregnant
      subjects (P<0.05). Moreover, a decrease of the baroreflex sensitivity was present
      in all pregnant women in the orthostatic position (P<0.05). In conclusion
      pregnancy per se is associated with a decrease in the baroreflex control of the
      heart, whereas in pre-eclampsia, the baroreflex sensitivity is impaired further.

PMID- 10204815
TI  - Baroreflex sensitivity and the blood pressure response to beta-blockade.
AB  - The objective of this analysis was to determine whether changes in baroreflex
      sensitivity (BRS) within 35 hypertensive patients (25 M, 10 F, mean age 47 years)
      treated with beta-blockade as monotherapy relate to reductions in ambulatory
      blood pressure (BP) or its variability. BP was recorded intra-arterially directly
      from the brachial artery before and during submaximal exercise. BRS was
      determined by the phenylephrine injection technique. MAP and its variability were
      determined for the awake period of 24-h BP monitoring. Subjects were randomised
      to one of atenolol, metoprolol, pindolol, or propranolol, and restudied after a
      mean of 5 months. Beta-blockade increased BRS in 24 patients and decreased BRS in
      11. BRS increased from 6.53+/-4.94 to 9.40+/-8.62 ms/mm Hg (mean +/- s.d.)
      (P<0.01). Waking ambulatory MAP decreased from 125.8+/-15.8 to 106.4+/-16.2 mm Hg
      (P<0.0001), but its variability did not change. Higher BRS after chronic beta
      blockade was associated with a decrease in waking ambulatory MAP (r = -0.55,
      P<0.001), but not with its variability (r = -0.08). Beta-blockade attenuated the
      pressor response to exercise, but there was a positive relationship between the
      effect of beta-blockade on BRS, and on the rise in systolic BP during bicycling
      (r = 0.63; P<0.001). Any dampening effect of beta-blockade on BP variability at
      rest in hypertensive patients with the greatest increase in BRS may be offset by
      increased pressor responses to physical activity such as exercise. Consequently,
      BP variability is unaffected, even though reductions in ambulatory BP during
      chronic beta-blockade are inversely related to changes in BRS. BP responses to
      beta-blockade may be a function of the action of this class of drugs on BRS.
      However, there is considerable variation, between subjects, in their effect on
      BRS. This may have implications for other conditions, such as dilated
      cardiomyopathy, or following myocardial infarction, in which improvement in BRS
      is one mechanism by which beta-adrenoceptor blockade could improve survival.

PMID- 10204816
TI  - The contribution of genes, environment and of body mass to blood pressure
      variance in young adult males.
AB  - OBJECTIVE: (1) To determine by means of multivariate genetic modelling whether
      the covariation of blood pressure (BP) and body mass index (BMI) is compatible
      with a direct effect of BMI on BP, or rather with pleiotropy or environmental
      association, and (2) to quantify the contribution of such an effect and of
      heritability and environmental factors to BP variance. DESIGN AND METHODS: Fifty
      monozygous and 41 dizygous male twin pairs (ages: 17-38 years) were studied. BMI
      was calculated as weight/height. Blood pressure was the mean of three
      conventional measurements in the supine position. Estimates for the path
      coefficients of the three hypothesised models were obtained using Maximum
      Likelihood Estimation and were used to calculate the predicted covariance
      matrices for these models. A chi2 goodness-of-fit index of P>0.05 indicated an
      adequate fit. Likelihood ratio chi2 statistics and the Akaike Information
      Criterion (AIC) were used to choose the best model among the fitting models. The
      path coefficients of the best model were used to estimate the variance
      decomposition of BP. RESULTS: All hypothesised models fitted the data. The AIC
      was lowest for the model representing an influence of BMI on BP, for both
      systolic (AIC = -22.3) and diastolic (AIC = -22.2) BP. The estimated percentages
      of the total phenotypic variance of BP, which could be explained by the influence
      of BMI on BP, were 11.4% and 12.9% for systolic and diastolic pressure
      respectively. The remaining variances were associated with variation in genetic
      and environmental factors. CONCLUSIONS: A direct influence of BMI on BP
      constitutes the most likely explanation of the BP-BMI-covariation and it accounts
      for about 12% of the BP-variance in young healthy men.

PMID- 10204817
TI  - Out-patient versus in-hospital ambulatory 24-h blood pressure monitoring in heart
      transplant recipients.
AB  - OBJECTIVE: To study the effect of the environment--in-hospital vs. out-patient
      situation--on blood pressure as measured by ambulatory blood pressure monitoring
      (ABPM). PATIENTS AND METHODS: Twenty-four hour ABPM was performed sequentially in
      hospital and again 9+/-3 days later on an out-patient basis, in 30 consecutive
      heart transplant recipients (27 men, median age 56 years, median time post
      transplant 3 years). The same equipment was used on both occasions, without any
      interim change in medical treatment. RESULTS: Both systolic and diastolic blood
      pressure were higher in-hospital than as an out-patient: +7+/-7 and +6+/-5 mm Hg
      respectively for the 24-h average (P<0.001). Daytime and night-time pressures
      were affected similarly. Depending on the specific cut-off values used, 37 to 87%
      of the individual patients were hypertensive in-hospital; 31 to 73% of these had
      an acceptable blood pressure as an out-patient. The converse was very rare (0 to
      3% of the total group). CONCLUSIONS: In heart transplant patients blood pressure
      as assessed from 24-h ABPM is lower in the home environment than during a
      hospital stay. The post-transplant attenuation of the circadian variation in
      blood pressure is not influenced by the environment. Checking an unsatisfactory
      in-hospital ABPM with an outpatient recording may obviate the need for an
      (intensified) antihypertensive treatment in a substantial number of patients.

PMID- 10204819
TI  - Dissection of the aorta.

PMID- 10204818
TI  - Effect of hydrosoluble coenzyme Q10 on blood pressures and insulin resistance in
      hypertensive patients with coronary artery disease.
AB  - In a randomised, double-blind trial among patients receiving antihypertensive
      medication, the effects of the oral treatment with coenzyme Q10 (60 mg twice
      daily) were compared for 8 weeks in 30 (coenzyme Q10: group A) and 29 (B vitamin
      complex: group B) patients known to have essential hypertension and presenting
      with coronary artery disease (CAD). After 8 weeks of follow-up, the following
      indices were reduced in the coenzyme Q10 group: systolic and diastolic blood
      pressure, fasting and 2-h plasma insulin, glucose, triglycerides, lipid
      peroxides, malondialdehyde and diene conjugates. The following indices were
      increased: HDL-cholesterol, vitamins A, C, E and beta-carotene (all changes
      P<0.05). The only changes in the group taking the B vitamin complex were
      increases in vitamin C and beta-carotene (P<0.05). These findings indicate that
      treatment with coenzyme Q10 decreases blood pressure possibly by decreasing
      oxidative stress and insulin response in patients with known hypertension
      receiving conventional antihypertensive drugs.

PMID- 10204820
TI  - Fixed low-dose perindopril 2 mg/indapamide 0.625 mg combination in very elderly
      hypertensives.

PMID- 10204822
TI  - Protein status of infants with phenylketonuria undergoing therapy.

PMID- 10204821
TI  - Persistent hypertensive non-dipper triggered by panic disorder.

PMID- 10204823
TI  - Head Start, nutrition, and problems of poverty in childhood.

PMID- 10204824
TI  - Protein status of infants with phenylketonuria undergoing nutrition management.
AB  - OBJECTIVES: The objectives of this study were to determine if Phenex-1, amino
      acid modified medical food with iron maintained normal indices of protein status
      in infants with phenylketonuria (PKU) and to investigate factors that influence
      plasma amino acid concentrations. METHODS: A study was conducted for six months
      in 35 infants with classical PKU diagnosed in the neonatal period. Diet diaries
      and plasma amino acid concentrations were obtained monthly. Blood for analysis of
      plasma albumin, blood urea nitrogen (BUN), retinol binding protein (RBP) and
      transthyretin was obtained at one, three and six months of study. RESULTS: Mean
      (+/-SEM) total daily intake of medical food and nutrients was 79+/-4 g; 17.3+/
      0.6 g protein, 660+/-18 kcal, 255+/-10 mg phenylalanine (Phe), and 1423+/-56 mg
      tyrosine (Tyr). Mean concentrations of plasma amino acids, except cystine (during
      entire study), glycine (first month) and Phe were in the normal range. Mean
      concentrations of plasma Phe were in the treatment range (120 to 360 micromol/L).
      Plasma concentrations of arginine, methionine, Phe, tryptophan, Tyr, and valine
      were positively correlated with intakes at various months of study.
      Concentrations of aspartic and glutamic acids, Phe, and Tyr were positively
      correlated and 17 amino acids were negatively correlated with the interval
      between feeding and blood draw. At six months of study, concentration of plasma
      albumin was 4.1+/-0.1 g/dL, RBP was 3.74+/-0.2 mg/dL, transthyretin was 17.9+/
      0.9 mg/dL, and urea nitrogen was 11.9+/-0.5 mg/dL. CONCLUSION: During study, all
      mean plasma indices of protein status were in normal reference ranges. Phenex-1
      supports normal mean plasma amino acid, albumin, RBP, transthyretin, and BUN
      concentrations when fed in adequate amounts.

PMID- 10204825
TI  - Nutrient intake of Head Start children: home vs. school.
AB  - OBJECTIVE: To determine mean intake of energy and protein, total fat, saturated
      fat, percent energy from total and saturated fat, cholesterol, carbohydrate,
      calcium, iron, zinc, folate, vitamins A, C, E, B-6 and B-12, thiamin, niacin,
      riboflavin, magnesium, sodium and fiber of preschool Head Start children at
      school and away from school. DESIGN: Twenty-four-hour food intakes for 358 Head
      Start children were obtained by observing food intake at school and acquiring
      intake recalls from parents or guardians specifying food their children consumed
      for the balance of the day. After determining group estimates of energy and
      nutrient intake, mean intake was compared to standard nutrient recommendations
      for the entire 24-hour day, i.e., for the time the children were in school and
      for the remaining hours away from school ("home" intake). SUBJECTS: The 358 Head
      Start children attended school either half-day (2- to 3-hour AM and PM sessions)
      or all-day (5 to 6 hours). STATISTICAL ANALYSES: Differences in nutrient intake
      among class times were analyzed using one-way analysis of variance (ANOVA)
      followed by Tukey's multiple comparison test. Differences with a p-value <0.05
      (two-tailed) were considered to be statistically significant. Total energy,
      protein, calcium, iron, zinc, vitamins A, C, E, B6, and B12, thiamin, niacin,
      riboflavin as well as folate and magnesium were compared to the Recommended
      Dietary Allowances for the 4- to 6-year-old age group. Other standards that were
      used for comparisons included the National Cholesterol Education Program (fat,
      saturated fat and cholesterol), the 1989 National Research Council's Diet and
      Health Report (carbohydrate and sodium) and the recommendation for fiber proposed
      by the American Health Foundation. RESULTS: At school, half-day children consumed
      up to 25% of the daily recommendation for energy and nutrients, while all-day
      children achieved at least a third of the recommended intakes. When intakes at
      home and school were combined, all three groups of children (AM, PM and all-day)
      exceeded dietary recommendations for protein, vitamins and minerals. Energy
      intake remained below 100% of the recommendation, while intake of total fat,
      saturated fat and cholesterol exceeded recommendations. APPLICATION: Further
      research is required to explore energy needs and determine nutritional status and
      nutrient needs of minority and low-income preschool children. Strategies are
      required to increase nutrient density, but not fat density, of meals and snacks
      served to children who attend day care for part of the day. Finally, school meals
      and nutrition education programs such as Team Nutrition should broaden their base
      to include healthful eating habits for all school children, including the very
      youngest children in preschool programs.

PMID- 10204826
TI  - Effects of resistance vs. aerobic training combined with an 800 calorie liquid
      diet on lean body mass and resting metabolic rate.
AB  - OBJECTIVE: Utilization of very-low-calorie diets (VLCD) for weight loss results
      in loss of lean body weight (LBW) and a decrease in resting metabolic rate (RMR).
      The addition of aerobic exercise does not prevent this. The purpose of this study
      was to examine the effect of intensive, high volume resistance training combined
      with a VLCD on these parameters. METHODS: Twenty subjects (17 women, three men),
      mean age 38 years, were randomly assigned to either standard treatment control
      plus diet (C+D), n = 10, or resistance exercise plus diet (R+D), n = 10. Both
      groups consumed 800 kcal/day liquid formula diets for 12 weeks. The C+D group
      exercised 1 hour four times/week by walking, biking or stair climbing. The R+D
      group performed resistance training 3 days/week at 10 stations increasing from
      two sets of 8 to 15 repetitions to four sets of 8 to 15 repetitions by 12 weeks.
      Groups were similar at baseline with respect to weight, body composition, aerobic
      capacity, and resting metabolic rate. RESULTS: Maximum oxygen consumption (Max
      VO2) increased significantly (p<0.05) but equally in both groups. Body weight
      decreased significantly more (p<0.01) in C+D than R+D. The C+D group lost a
      significant (p<0.05) amount of LBW (51 to 47 kg). No decrease in LBW was observed
      in R+D. In addition, R+D had an increase (p<0.05) in RMR O2 ml/kg/min (2.6 to
      3.1). The 24 hour RMR decreased (p<0.05) in the C+D group. CONCLUSION: The
      addition of an intensive, high volume resistance training program resulted in
      preservation of LBW and RMR during weight loss with a VLCD.

PMID- 10204827
TI  - Perinatal vitamin D and calcium status of northern Canadian mothers and their
      newborn infants.
AB  - OBJECTIVE: This study was undertaken to examine the vitamin D and calcium status
      of mothers and their newborns. METHODS: The intakes of vitamin D and calcium were
      determined prenatally in 121 women including 33 Caucasians, 51 Inuits, and 37
      Native Indians, living in the Inuvik zone of the Northwest Territories. Plasma
      concentrations of 25-(OH)-D and calcium were also measured in mothers as well as
      in their offspring at delivery. RESULTS: The daily mean vitamin D intake of
      native mothers, including Inuits and Indians, with (8.1+/-5.5 microg) and without
      supplements (3.4+/-2.5 microg) was significantly lower than that of non-native
      mothers (13.2+/-5.9 microg and 5.8+/-4.3 microg, respectively). According to the
      predicted prevalence of low vitamin D intake, there existed a higher risk of
      vitamin D deficiency without supplementation in both native (88.6% vs 48.4%) and
      non-native (63.5% vs. 15.1%) mothers. The trend for calcium intakes with and
      without supplementation was similar to vitamin D intake. At the point of
      delivery, the plasma levels of 25-(OH)-D were lower in native mothers (50.1 19.3
      nmol/L) and their offspring (34.2+/-13.1 nmol/L) than their counterparts (59.8+/
      29.4 nmol/L and 41.4+/-23.5 nmol/L, respectively). Its plasma levels in newborn
      infants averaged only 67% of their mothers. None of these infants showed clinical
      evidence of vitamin D deficiency. In fact, their plasma calcium levels were
      significantly higher than their mothers. CONCLUSIONS: Plasma 25-(OH)-D
      concentrations of 60 to 70% of maternal levels may represent a "normal" range for
      newborn infants. However, a supplementation in native northern Canadian mothers
      during pregnancy and in their neonates during infancy may have a role to play in
      the prevention of vitamin D deficiency.

PMID- 10204828
TI  - Risk factors for cardiovascular disease and diabetes in two groups of Hispanic
      Americans with differing dietary habits.
AB  - OBJECTIVE: The purpose of this study was to determine if Hispanic Seventh-Day
      Adventists (SDAs), who typically eat a diet lower in fat, saturated fat and
      protein, and higher in complex carbohydrates and dietary fiber than the usual
      omnivorous diet, exhibit lower risk factors for cardiovascular disease (CVD) and
      Type 2 diabetes compared to Hispanic Catholic omnivores. METHODS: Anthropometric
      characteristics, dietary intake, blood pressure, serum lipids, glucose and
      insulin, as well as plasma ascorbic acid and vitamin E concentrations, were
      measured in two groups of Hispanic study participants residing in Denver,
      Colorado: 74 SDA study participants (x age: 42+/-1.5 y) and 45 Catholic
      participants (x age: 44+/-2.2 y). RESULTS: The SDAs reported lower dietary
      intakes of total fat, saturated fat and cholesterol and higher relative intakes
      of carbohydrate and dietary fiber compared to their Catholic counterparts. The
      SDAs exhibited significantly lower body mass index (BMI = 27.2+/-0.6) and waist
      to-hip ratios (WHR = 0.84+/-0.01) compared to the Catholics (BMI = 31.4+/-1.1;
      WHR = 0.88+/-0.01). The SDAs, compared to the Catholics, had lower fasting
      insulin (11.4+/-0.6 vs. 18.9+/-3.1 microu/ml) and glucose concentrations (88.6+/
      1.1 vs. 104.1+/-5.4 mg/dl). The SDA Hispanics, compared to the Catholic
      Hispanics, exhibited significantly lower values for systolic blood pressure (SBP
      = 1102 vs. 118+/-3 mm Hg), serum total cholesterol (STC = 198+/-5 vs. 214+/-6
      mg/dl) and serum triglycerides (TG = 152+/-12 vs. 232+/-27) and higher serum
      concentrations of high-density lipoprotein cholesterol (HDL-C = 44.7+/-1.3 vs.
      39.1+/-1.4 mg/dl) and ascorbic acid (1.14+/-0.08 vs. 0.87+/-0.07 mg/dl). Low
      density lipoprotein cholesterol (LDL-C) and vitamin E concentrations were not
      significantly different between groups, but the SDAs exhibited lower ratios of
      STC/HDL-C and LDL-C/HDL-C. CONCLUSION: Hispanic American SDAs, who eat a plant
      based diet, exhibit a more favorable blood lipid profile, lower blood pressure
      and lower risk for Type 2 diabetes compared to Hispanic American Catholics, who
      do not eat a plant-based diet.

PMID- 10204829
TI  - Red wine inhibits the cell-mediated oxidation of LDL and HDL.
AB  - OBJECTIVE: We compared the in vitro effects of red wine, white wine and ethanol
      on the cell mediated oxidation of low-density lipoprotein (LDL) and high-density
      lipoprotein (HDL) by three frequently-used assays. METHODS: LDL and HDL isolated
      from normolipidemic human serum were incubated with J774.A1 macrophages in DMEM
      with copper, with or without red wine, white wine or ethanol (equivalent to 0.2
      mg ethanol/ml). Lipoprotein oxidation was assessed by conjugated diene formation
      as measured by changes in absorbance at 234 nm (deltaA234), thiobarbituric-acid
      reactive-substance (TBARS) production and trinitrobenzene-sulfonic-acid (TNBS)
      reactivity. RESULTS: Red wine (0.2 mg ethanol/mL) inhibited LDL oxidation as
      indicated by an 85.7% decrease in absorbance at 234 nm, a 96.5% decrease in TBARS
      production and complete prevention of the decrease in TNBS reactivity. White wine
      and ethanol did not have any significant effect at 0.2 mg/mL. White wine at 1.0
      mg ethanol/mL inhibited TBARS production from LDL by 84.1%. Red wine (0.2 mg
      ethanol/mL) inhibited HDL oxidation as indicated by a 78.9% decrease in
      deltaA234, an 81.7% decrease in TBARS production and by no change in TNBS
      reactivity. White wine and ethanol had no effect at 0.2 mg/mL. White wine at 1.0
      mg ethanol/mL inhibited TBARS production from HDL by 66.4%. CONCLUSIONS: These
      results indicate that red wine inhibits the cell mediated oxidation of
      lipoproteins, that white wine is not as effective as red wine and that the effect
      of the red wine is not due to its ethanol content.

PMID- 10204830
TI  - The influence of dietary restriction on vitamin B-6 vitamer distribution and on
      vitamin B-6 metabolizing enzymes in rats.
AB  - OBJECTIVE: The purpose of this study was to assess the effect of dietary
      restriction on tissue distribution of vitamin B-6 vitamers and activities of
      vitamin B-6 metabolizing enzymes in rats. METHODS: Male rats were subjected to a
      40% dietary restriction for 10, 20 or 40 weeks. The tissue vitamin B-6 vitamer
      concentrations and activities of the vitamin B-6 metabolizing enzymes of the
      animals were determined. RESULTS: The plasma pyridoxal 5'-phosphate (PLP)
      concentrations of the diet-restricted (DR) rats were comparable to those of the
      control group at week ten but were significantly lower at weeks 20 and 40. These
      significantly lower levels of plasma PLP in DR rats might in part be related to
      lower hepatic pyridoxal kinase and pyridoxamine (pyridoxine) 5'-phosphate oxidase
      activities. The urinary 4-pyridoxic acid excretion of the DR groups responded to
      the reduced food intake and were lower at weeks 10 and 20. Tissue levels of PLP
      were not affected by dietary restriction. In contrast, greater levels of
      pyridoxamine 5'-phosphate were found in liver, kidney and heart of the DR
      animals. CONCLUSION: The duration of dietary restriction influenced the
      distribution of vitamin B-6 vitamers. When plasma PLP is used to evaluate vitamin
      B-6 status, the length of dietary restriction should be considered.

PMID- 10204831
TI  - Antioxidant-like properties of zinc in activated endothelial cells.
AB  - OBJECTIVE: The objective of this study was to test the hypothesis that zinc
      deficiency in endothelial cells may potentiate the inflammatory response mediated
      by certain lipids and cytokines, possibly via mechanisms associated with
      increased cellular oxidative stress. Our experimental approach was to compare
      conditions of cellular zinc deficiency and zinc supplementation with oxidative
      stress-mediated molecular and biochemical changes in vascular endothelial cells.
      METHODS: To investigate our hypothesis, porcine pulmonary artery-derived
      endothelial cells were depleted of zinc by culture in media containing 1% fetal
      bovine serum for eight days. Subsequently, endothelial cells were exposed to
      media enriched with or without zinc (10 microM) for two days, followed by
      exposure to either tumor necrosis factor-alpha (TNF, 500 U/mL) or linoleic acid
      (90 microM), before measurement of oxidative stress (DCF fluorescence),
      activation of nuclear factor kappaB (NF-kappaB) or activator protein-1 (AP-1) and
      production of the inflammatory cytokine interleukin 6 (IL-6). RESULTS: Oxidative
      stress was increased markedly in zinc-deficient endothelial cells following
      treatment with fatty acid or TNF. This increase in oxidative stress was partially
      blocked by prior zinc supplementation. The oxidative stress-sensitive
      transcription factor NF-kappaB was up-regulated by zinc deficiency and fatty acid
      treatment. The up-regulation mediated by fatty acids was markedly reduced by zinc
      supplementation. Similar results were obtained with AP-1. Furthermore,
      endothelial cell production of IL-6 was increased in zinc-deficient endothelial
      cells following treatment with fatty acids or TNF. This increase in production of
      inflammatory cytokines was partially blocked by zinc supplementation. DISCUSSION:
      Our previous data clearly show that zinc is a protective and critical nutrient
      for maintenance of endothelial integrity. The present data suggest that zinc may
      in part be antiatherogenic by inhibiting oxidative stress-responsive events in
      endothelial cell dysfunction. This may have implications in understanding
      mechanisms of atherosclerosis.

PMID- 10204832
TI  - Effect of wheat bran on serum lipids: influence of particle size and wheat
      protein.
AB  - OBJECTIVE: Wheat fiber appears to protect from cardiovascular disease despite its
      lack of consistent effect on serum lipids. We therefore wished to determine
      whether reported inconsistencies in the effect of wheat bran resulted from
      differences in particle size or its high gluten content. METHODS: Two studies
      were conducted. In one-month metabolic diets, 24 hyperlipidemic subjects consumed
      breads providing an additional 19 g/d dietary fiber as medium or ultra-fine wheat
      bran and extra protein (10% of energy as wheat gluten). In two-week ad libitum
      diets, 24 predominantly normolipidemic subjects consumed breakfast cereals
      providing an additional 19 g/d of dietary fiber as coarse or a mixture of ultra
      fine and coarse wheat bran with no change in gluten intake. Both studies followed
      a randomized crossover design with control periods when subjects ate low-fiber
      breads and cereals respectively with no added gluten. Fasting blood lipids were
      measured on day zero and at the end of each phase. RESULTS: Wheat bran had no
      effect on total, LDL or HDL cholesterol irrespective of particle size or level of
      gluten in the diet. However, consumption of increased gluten in the metabolic
      study was associated with a 13+/-4% reduction in serum triglycerides (p = 0.005)
      which was not seen in the normal-gluten ad libitum study. CONCLUSIONS: The
      protective effect of wheat fiber in cardiovascular disease cannot be explained by
      an effect of wheat bran in reducing serum cholesterol although in hyperlipidemic
      subjects displacement of carbohydrate by gluten on the high-fiber phases was
      associated with lower serum triglycerides.

PMID- 10204833
TI  - The effect of ascorbic acid supplementation on the blood lead levels of smokers.
AB  - BACKGROUND: The study subjects were 75 adult men (20 to 30 years of age), who
      smoked one pack of cigarettes per day (minimum) and had no clinical signs of
      ascorbic acid deficiency or lead toxicity. None had a history of industrial
      exposure to lead, and the blood-lead levels were anticipated to be below 1.45
      micromol/L, the minimum blood level associated with toxicity symptoms. METHODS:
      The men were randomly assigned to three study groups of 25, and each group was
      provided a four-week supply of one level of daily ascorbic acid supplements
      (placebo, 200 mg or 1000 mg of ascorbic acid). We measured baseline and weekly
      serum and urine ascorbic-acid levels as well as blood and urine lead levels. The
      weekly group means and variations of the measured data were statistically
      compared by means of ANOVA and Pearson's correlation. RESULTS: The serum ascorbic
      acid levels of the groups receiving ascorbic acid increased significantly after
      one week (p< or =.001). There was no effect of placebo or 200 mg ascorbic-acid
      supplementation on the blood or urine lead levels. However, there was a 81%
      decrease in blood-lead levels in the 1000 mg ascorbic acid group after one week
      of supplementation (p< or =.001). CONCLUSIONS: Daily supplementation with 1000 mg
      of ascorbic acid results in a significant decrease of blood-lead levels
      associated with the general population. Ascorbic acid supplementation may provide
      an economical and convenient method of reducing blood-lead levels, possibly by
      reducing the intestinal absorption of lead.

PMID- 10204834
TI  - Breakfast type, daily nutrient intakes and vitamin and mineral status of French
      children, adolescents, and adults.
AB  - OBJECTIVE: To examine associations between the consumption of different types of
      breakfasts, dietary intakes, and selected indices of nutritional status. METHODS:
      Dietary intakes were obtained using the dietary history method, and serum
      bioassays were used to assess vitamin and mineral status in a representative
      community-based sample of 1108 French children (ages 2 to 10 years), adolescents
      (ages 10 to 18 years), and adults (ages 18 to 65 years). Breakfasts were divided
      into three categories: low-energy (<15% of the energy RDA), medium-energy (15
      25%) and high-energy (>25%). RESULTS: High-energy breakfasts were associated with
      the consumption of ready-to-eat (RTE) cereals. High-energy breakfasts and cereal
      consumption, both more common among children and adolescents than among adults,
      were also associated with a greater proportion of daily energy from carbohydrate
      and lower proportion of energy from fat. High-energy breakfasts and cereal
      consumption were further associated with higher intakes of vitamins and minerals
      as measured by percent RDAs. High-energy breakfasts and cereal consumption were
      associated with lower serum cholesterols and improved biochemical indices of
      nutritional status. Serum concentrations of vitamin B1 (in children and
      adolescents), vitamin B2 and beta-carotene (in adults) were significantly linked
      to the level of energy provided by breakfast. CONCLUSION: The consumption of
      breakfast cereals appears to have a positive impact on nutritional status
      regardless of age.

PMID- 10204835
TI  - Sweetener augmentation of serum triacylglycerol during a fat challenge test in
      humans.
AB  - OBJECTIVE: High concentrations of fructose enhance postprandial lipemia following
      lipid loading whereas glucose exerts a negative or minimal effect. This study
      evaluated the effect of lower sweetener concentrations and the contribution of
      their sweetness level and palatability. METHODS: At each of four test sessions,
      twelve male and ten female healthy adults ingested one of four milkshakes
      containing 108 g dairy cream alone or supplemented with 30 g fructose, 17.5 g
      glucose or 1 g aspartame. Blood samples were collected at baseline, two, four,
      six and eight hours after ingestion. Sensory discrimination tests were conducted
      after the last two sessions. RESULTS: Fructose and glucose led to 37% (p = 0.03)
      and 59% (p = 0.08) rises in triacylglycerol area under the curve (TG AUC) when
      compared to the plain milkshake, respectively. Although the sweetened shakes were
      equisweet and were more palatable than the plain shake, the TG rise after the
      aspartame milkshake did not differ from the plain milkshake. CONCLUSIONS: These
      data indicate that low levels of glucose and fructose consumed with lipid enhance
      postprandial lipemia. Sweetness and palatability did not account for the effect.

PMID- 10204836
TI  - Anorexia nervosa treated in a foster house setting: a case report.

PMID- 10204838
TI  - Obesity concerns, weight satisfaction and characteristics of female dieters: a
      study on female Taiwanese college students.
AB  - OBJECTIVE: This study was designed to obtain baseline data regarding desired body
      weight, weight satisfaction, self-perceived weight categories, approaches to
      weight loss of female college students in Taiwan. The characteristics of subjects
      who are dieting were also assessed. METHODS: One thousand, fifty-seven female
      college students participated in this study. Written questionnaires were used for
      data collection. Students' height and weight were also measured. Simple frequency
      and one-way analysis of variance (ANOVA) were used to analyze data. Post hoc
      analyses were performed with the LSD test when the F ratio for the ANOVA was
      significant at p<0.05. RESULTS: In general, subjects perceived themselves as
      being heavier than their actual weight categories. The percentage of subjects who
      perceived they were overweight or obese was much higher than the percentage of
      subjects who were actually in these categories (51.4% vs. 16.2%). Above 20% of
      subjects in both severely underweight and underweight categories use some methods
      to lose weight. More than 60% of subjects in acceptable weight categories still
      want to lose weight. A higher percentage of subjects chose exercise than dieting
      as the major weight-loss method. Subjects in the DS/D (dissatisfied/dieting)
      group did not score higher points for knowledge and attitude in nutrition, and
      they tended to measure their body weight more frequently (p<0.05), spent more
      time for exercise (p<0.05) and for reading nutrition information (p<0.05); they
      also skipped lunch (p<0.05) more frequently than others. CONCLUSIONS: The results
      indicate that risk factors leading to eating disorders are common among Taiwanese
      college females. Dietitians, physicians and other health professionals should be
      on the alert to identify patients with eating disorders.

PMID- 10204837
TI  - Thyroid function and energy intake during weight gain following treatment of
      hyperthyroidism.
AB  - OBJECTIVE: Individuals with hyperthyroidism lose weight despite increased
      appetite and food intake, and weight is regained after treatment of
      hyperthyroidism. We asked whether this weight regain is purely a function of
      lowered metabolic rate coincident with lowered thyroid hormone concentrations or
      if the weight gain is related to food-energy overconsumption. METHODS: Ten
      unselected patients with hyperthyroidism treated with 131I were studied. The
      following measurements were made at 0, 1, 2, 3, 6, and 12 months: total food
      energy, carbohydrate, fat and protein consumption; serum thyroxine (T4); serum
      triiodothyronine (T3); T3 resin uptake; serum thyroid stimulating hormone (TSH);
      weight; height; and 24-hour urinary urea excretion. RESULTS: Inverse changes in
      body weight and food energy consumption/kg throughout the period of observation
      was a striking finding (mean initial weight 67.1+/-5 kg, final weight 76.4 kg+/-3
      kg, premorbid weight 77.1+/-5 kg). The initial and final food energy intake was
      3005+/-199 and 2597+/-137 Kcal/24 hrs, respectively. The thyroid hormone
      concentrations declined inversely relative to weight gain during the first months
      of the study, but later the thyroid hormones increased while weight gain
      continued. Initial serum T4 15.0+/-1 value at three months was 4.0+/-1.0 mg/dl,
      final T4 11.0+/-1. CONCLUSION: We conclude that weight gain following treatment
      of hyperthyroidism is due to 1) reduction in metabolic rate consequent upon the
      decreased thyroid hormone concentrations and 2) food energy intake which was
      initially greater than required to maintain individuals' premorbid weight. As
      body weight increased, food intake declined and both reached an asymptotic limit.

PMID- 10204839
TI  - Knee height as a predictor of recumbent length for individuals with mobility
      impaired cerebral palsy.
AB  - BACKGROUND: Because accurate measures of recumbent length are essential to assess
      growth and energy requirements of mobility-impaired individuals with cerebral
      palsy (CP), a reliable and simple method of estimating recumbent length is
      required. Prediction of recumbent length from knee height in this population has
      not yet been investigated. OBJECTIVES: i) To correlate direct measures of
      recumbent length in mobility-impaired individuals having lower leg extremity
      cerebral palsy (LECP) involvement with indirect measures of recumbent length
      calculated using knee-height prediction equations and ii) to determine if knee
      height is a reliable predictor of recumbent length in this population. METHODS:
      Subjects (n = 34; 15F, 19M), aged 6 to 30 years, were participants in a six-month
      nutrition rehabilitation program. All subjects had varying degrees of LECP
      involvement. Recumbent length to the nearest 0.5 cm was measured by standardised
      techniques. Knee height was measured to the nearest 0.5 centimetre using sliding
      callipers. Equations based on normal, healthy individuals with application to
      mobility-impaired or handicapped individuals were used to predict recumbent
      length from knee height. RESULTS: Direct measures of recumbent length of subjects
      significantly correlated with indirect measures calculated using knee height
      prediction equations (R = 0.88, p< or =0.0001). In addition, knee height of these
      subjects was a reliable predictor of recumbent length (R2 = 0.78, p<0.0001).
      CONCLUSIONS: Results suggest that knee height may be a reliable predictor for
      recumbent length in this population.

PMID- 10204840
TI  - Cleidocranial dysplasia: clinical and molecular genetics.
AB  - Cleidocranial dysplasia (CCD) (MIM 119600) is an autosomal dominant skeletal
      dysplasia characterised by abnormal clavicles, patent sutures and fontanelles,
      supernumerary teeth, short stature, and a variety of other skeletal changes. The
      disease gene has been mapped to chromosome 6p21 within a region containing CBFA1,
      a member of the runt family of transcription factors. Mutations in the CBFA1 gene
      that presumably lead to synthesis of an inactive gene product were identified in
      patients with CCD. The function of CBFA1 during skeletal development was further
      elucidated by the generation of mutated mice in which the Cbfa1 gene locus was
      targeted. Loss of one Cbfa1 allele (+/-) leads to a phenotype very similar to
      human CCD, featuring hypoplasia of the clavicles and patent fontanelles. Loss of
      both alleles (-/-) leads to a complete absence of bone owing to a lack of
      osteoblast differentiation. These studies show that haploinsufficiency of CBFA1
      causes the CCD phenotype. CBFA1 controls differentiation of precursor cells into
      osteoblasts and is thus essential for membranous as well as endochondral bone
      formation.

PMID- 10204841
TI  - Evaluation of a mutation screening strategy for sporadic cases of ATR-X syndrome.
AB  - We report on the evaluation of a strategy for screening for XNP/ATR-X mutations
      in males with mental retardation and associated dysmorphology. Because nearly
      half of the mutations in this gene reported to date fall into a short 300 bp
      region of the transcript, we decided to focus in this region and to extend the
      mutation analysis to cases with a negative family history. This study includes 21
      mentally retarded male patients selected because they had severe mental
      retardation and a typical facial appearance. The presence of haemoglobin H or
      urogenital abnormalities was not considered critical for inclusion in this study.
      We have identified six mutations which represents a mutation detection rate of
      28%. This figure is high enough for us to propose this strategy as a valid first
      level of screening in a selected subset of males with mental retardation. This
      approach is simple, does not require RNA preparation, does not involve time
      consuming mutation detection methods, and can thus be applied to a large number
      of patients at a low cost in any given laboratory.

PMID- 10204842
TI  - Deletion mapping and X inactivation analysis of a non-specific mental retardation
      gene at Xp21.3-Xp22.11.
AB  - We report on deletion mapping and X inactivation analysis of a gene for X linked
      non-specific mental retardation (MRX) at Xp21.3-Xp22.11, on the basis of
      molecular studies in two families with Xp microdeletions involving the DAX-1
      gene. In family A, mental retardation (MR) was profound in the older brother with
      an episode of adrenal crisis, severe in the younger brother with no episode of
      adrenal crisis, and mild to moderate in the sister and the mother with no signs
      of adrenal hypoplasia. In family B, MR was absent in the male patient with
      adrenal hypoplasia. Polymerase chain reaction for 16 loci in the middle of Xp
      showed that the brothers of family A had a small Xp deletion between DXS7182 and
      DXS1022, and that the patient of family B had a tiny Xp deletion between DXS319
      and DXS1022. Microsatellite analysis for tetranucleotide repeats in the promoter
      region of the DAX-1 gene and Southern blotting for DAX-1 and DXS28 showed that
      the sister and the mother of family A were heterozygous for the interstitial
      deletion. X inactivation analysis for the methylation status of the AR gene and
      the HPRT gene indicated that the normal X and the deleted X chromosome underwent
      random X inactivation in both the sister and the mother. The results imply that
      an MRX gene subject to X inactivation is present in a roughly 4 Mb region between
      DXS7182 and DAX-1, and that reduced expression of the normal MRX gene caused by
      random X inactivation results in MR in carrier females.

PMID- 10204843
TI  - Localisation of a gene for transient neonatal diabetes mellitus to an 18.72
      cR3000 (approximately 5.4 Mb) interval on chromosome 6q.
AB  - Transient neonatal diabetes mellitus (TNDM) is a rare condition which presents
      with intrauterine growth retardation, dehydration, and failure to thrive. The
      condition spontaneously resolves before 1 year of age but predisposes patients to
      type 2 diabetes later in life. We have previously shown that, in some cases, TNDM
      is associated with paternal uniparental disomy (UPD) of chromosome 6 and
      suggested that an imprinted gene responsible for TNDM lies within a region of
      chromosome 6q. By analysing three families, two with duplications (family A and
      patient C) and one with several affected subjects with normal karyotypes (family
      B), we have further defined the TNDM critical region. In patient A, polymorphic
      microsatellite repeat analysis identified a duplicated region of chromosome 6,
      flanked by markers D6S472 and D6S311. This region was identified on the Sanger
      Centre's chromosome 6 radiation hybrid map (http://www.sanger.ac.uk/HGP/Chr6) and
      spanned approximately 60 cR3000. Using markers within the region, 418 unique P1
      derived artificial chromosomes (PACs) have been isolated and used to localise the
      distal breakpoints of the two duplications. Linkage analysis of the familial case
      with a normal karyotype identified a recombination within the critical region.
      This recombination has been identified on the radiation hybrid map and defines
      the proximal end of the region of interest. We therefore propose that an
      imprinted gene for TNDM lies within an 18.72 cR3000 (approximately 5.4 Mb)
      interval on chromosome 6q24.1-q24.3 between markers D6S1699 and D6S1010.

PMID- 10204844
TI  - A clinical study of type 1 neurofibromatosis in north west England.
AB  - A clinical study of patients on the North West Regional Genetic Register with
      neurofibromatosis type 1 (NF1) identified 523 affected cases from 304 families.
      In those for whom relevant information was available, 86.7% (383 of 442) had more
      than six cafe au lait patches, 83.8% (310 of 370) had axillary freckling, 42.3%
      (151 of 357) had inguinal freckling, and 63% (157 of 249) had Lisch nodules.
      Cutaneous neurofibromas were present in 59.4% (217 of 365) and 45.5% (150 of 330)
      were noted to have subcutaneous tumours. Plexiform neurofibromas were present in
      15.3% (80 of 523). A positive family history of NF1 was found in 71.2% (327 of
      459) and 28.8% (132 of 459) of affected patients were considered to be the result
      of a new mutation. Learning difficulties of varying severity occurred in 62% (186
      of 300). CNS tumours associated with NF1 were reported in 9.4% (49) of patients,
      optic gliomas occurring in 25 of these, 4.8% of patients. Some degree of
      scoliosis was reported for 11.7% (61), 1.9% (10) had pseudoarthrosis, 4.3% (23)
      had epilepsy, and 2.1% (11) had spinal neurofibromas. Actuarial analyses were
      carried out for both optic glioma and malignant nerve sheath tumours and the data
      are presented.

PMID- 10204845
TI  - An analysis of common isodisomic regions in five mUPD 16 probands.
AB  - Intrauterine growth retardation (IUGR) with or without additional abnormalities
      is recognised as a common feature of maternal uniparental disomy for chromosome
      16 (mUPD 16) and is usually associated with confined placental mosaicism (CPM).
      Although it is likely that the CPM largely contributes to the IUGR, postnatal
      growth retardation and other common abnormalities may also be attributed to the
      mUPD. Five cases with mUPD 16 and CPM were analysed for common regions of
      isodisomy using polymorphic markers distributed along the length of the
      chromosome. In each case the aberration was consistent with a maternal meiosis I
      error. Complete isodisomy was not detected in any of the patients although two
      patients were found to be mixed with both iso- and heterodisomy. Interestingly,
      the patient with the greater region of isodisomy was the most severely affected.
      The fact that there were no common regions of isodisomy in any of the patients
      supports the hypothesis that imprinted genes, rather than recessive mutations,
      may play a role in the shared phenotypes.

PMID- 10204846
TI  - A genetic study of the human T gene and its exclusion as a major candidate gene
      for sacral agenesis with anorectal atresia.
AB  - Sacral agenesis is a heterogeneous group of congenital anomalies in which most
      cases are sporadic but rare familial forms also occur. Although one gene has been
      mapped to chromosome 7q36 in families with hemisacrum, associated with anorectal
      atresia and presacral mass, it is clear that the genetic aetiology of these
      disorders is complex and other genes remain to be discovered. Some years ago, the
      idea of T (Brachyury) as a candidate gene for sacral agenesis was raised, because
      tail abnormalities associated with T and the t complex, on mouse chromosome 17,
      resemble spinal defects seen in man. The recent cloning and mapping of the human
      T gene prompted us to re-evaluate this idea. T is a transcription factor
      essential for the normal development of posterior mesodermal structures. Although
      the sequence and function of T are highly conserved in evolution, our genetic
      study shows that the coding region of the human gene is highly polymorphic. Three
      common variable amino acid sites in known functional domains have been
      identified: Gly356Ser, Asn369Ser, and Gly177Asp. For the latter variant,
      functional studies have shown that the presence of Asp at residue 177 reduces the
      stability of T dimer formation. A search for rare mutation of T in 28 selected
      patients with sacral agenesis/anorectal atresia identified a novel, rare variant
      in one patient and her mother. This mutation leads to an amino acid change within
      a conserved activation domain. While the functional significance of this single
      mutation requires further investigation, we can conclude from our studies that if
      T has a role in the aetiology of sacral agenesis, its contribution is small in
      this particular set of patients. However, we cannot exclude a more major role in
      other forms of sacral defect.

PMID- 10204847
TI  - Genetic analysis of the 3' untranslated region of the tumour necrosis factor
      shows a highly conserved region in rheumatoid arthritis affected and unaffected
      subjects.
AB  - Tumour necrosis factor (TNF) is a key proinflammatory mediator in rheumatoid
      arthritis (RA). The TNF locus, situated in the class III region of the MHC, is
      flanked by five microsatellite markers. It has previously been shown that this
      region influences susceptibility to RA; two TNF microsatellite haplotypes were
      found to be associated with RA. Evidence from murine studies has indicated that
      variation in the TNF 3' untranslated region (UTR) could be associated with
      altered regulation of TNF biosynthesis. In order to identify possible RA
      associated polymorphisms, more than 800 bp of the TNF 3' UTR was genetically
      analysed in RA affected and unaffected subjects possessing specific RA and non-RA
      associated TNF microsatellite haplotypes. The TNF 3' UTR region was analysed
      using two mutation detection methods, PCR-SSCP and NIRCA analysis and DNA
      sequencing. No genetic differences were observed in the human TNF 3' UTR between
      subjects, that is, irrespective of RA status or TNF haplotype, and also compared
      with previously published TNF sequences from human sources. Therefore it can be
      concluded that the TNF 3' UTR in this population was highly conserved and did not
      influence susceptibility to RA.

PMID- 10204849
TI  - A Hirschsprung disease locus at 22q11?
AB  - We report a boy with truncus arteriosus, dysmorphic features, developmental
      delay, passing hypotonia, short segment Hirschsprung disease (HSCR), and
      paroxysmal hypoventilation. FISH analysis showed an interstitial deletion in
      chromosome band 22q11.2 coinciding with the deletions found in DiGeorge syndrome
      and velocardiofacial syndrome. Mutation scanning of RET, GDNF, EDNRB, and EDN3,
      genes associated with Hirschsprung disease, showed no aberrations. Since we know
      of two more patients with velocardiofacial syndrome and HSCR, we hypothesise that
      a gene responsible for proper development of the enteric nervous system may be
      included in the 22q11.2 region.

PMID- 10204848
TI  - Investigation of germline GFR alpha-1 mutations in Hirschsprung disease.
AB  - Inactivating mutations of the RET proto-oncogene and of one of its soluble ligand
      molecules, glial cell line derived neurotrophic factor (GDNF), have been found in
      a subset of patients with Hirschsprung disease (HSCR). However, the majority of
      HSCR mutations remain unidentified. As normal RET function requires a
      multicomponent ligand complex for activation, other members of the RET ligand
      complex are primary candidates for these mutations. We investigated the presence
      of mutations in another member of the RET signalling complex, GDNF family
      receptor alpha-1 (GFR alpha-1), in a panel of 269 independent cases of HSCR. We
      identified 10 polymorphisms at the GFR alpha-1 locus. Surprisingly, however, we
      did not identify any sequence variants in our HSCR population that were not also
      present in a normal control population. Our data suggest that mutations of the
      GFR alpha-1 gene are not a common aetiological event in HSCR.

PMID- 10204850
TI  - The inheritance of migraine with aura estimated by means of structural equation
      modelling.
AB  - Studies of migraine with aura (MA) have shown familial aggregation of the
      disorder, which cannot be explained by simple mendelian inheritance. The interest
      in a genetic basis for the disorder has increased after identification of three
      genetic loci for familial hemiplegic migraine (FHM), which is a rare subtype of
      MA with autosomal dominant inheritance. Both genetic and environmental factors
      seem to be important in the expression of MA. To elucidate the molecular
      pathogenesis of MA, knowledge of the relative role of genetic and environmental
      factors is essential. Twin studies are a classic way to analyse this. We applied
      structural equation modelling on MA with twin data obtained from a population
      based twin register in order to evaluate the effects of genes and environment.
      The correlation in liability of MA was 0.68 in monozygotic (MZ) and 0.22 in
      dizygotic (DZ) twin pairs, indicating a high degree of genetic determination in
      the total variance of liability. The best fitting model combined additive genetic
      effects and environmental effects that were not shared by the twins. The estimate
      of heritability was 0.65 and similar in males and females.

PMID- 10204852
TI  - De novo deletion (14)(q11.2q13) including PAX9: clinical and molecular findings.
AB  - A 3 year old boy with a de novo deletion (14)(q11.2q13) of paternal origin
      encompassing the region from D14S264 to D14S70 is described. The patient
      presented with severe psychomotor retardation, bilateral cleft lip/palate,
      bilateral colobomas of the optic nerves and retinas, agenesis of the corpus
      callosum, pes calcaneovarus, reduced oesophageal peristalsis, and swallowing
      difficulties. This is the first reported case of PAX9 hemizygosity in humans.
      Haploinsufficiency of the PAX9 gene might be expected to cause some of the
      developmental defects and the dysphagia. Another haploinsufficiency candidate
      gene, the bZIP transcription factor gene NRL, which is specifically expressed in
      neuronal cells and the eye during embryogenesis, was excluded from the deletion
      interval.

PMID- 10204851
TI  - Mutations in the cationic trypsinogen gene and evidence for genetic heterogeneity
      in hereditary pancreatitis.
AB  - Hereditary pancreatitis (HP) is a rare inherited disorder, characterised by
      recurrent episodes of pancreatitis often beginning in early childhood. The mode
      of inheritance suggests an autosomal dominant trait with incomplete penetrance.
      The gene, or at least one of the genes, responsible for hereditary pancreatitis
      has been mapped to the long arm of chromosome 7 and a missense mutation, an
      arginine to histidine substitution at residue 117 in the trypsinogen cationic
      gene (try4) has been shown to segregate with the HP phenotype. The aim of this
      work was to investigate the molecular basis of hereditary pancreatitis. This
      study was performed on 14 HP families. The five exons of the trypsinogen cationic
      gene were studied using a specific gene amplification assay combined with
      denaturing gradient gel electrophoresis (DGGE). The present paper describes three
      novel mutations, namely K23R and N29I and a deletion -28delTCC in the promoter
      region. We also found a polymorphism in exon 4, D162D. In eight of these families
      we found a mutation which segregates with the disease. A segregation analysis
      using microsatellite markers carried out on the other families suggests genetic
      heterogeneity in at least one of them. Our findings confirm the implication of
      the cationic trypsinogen gene in HP and highlight allelic diversity associated
      with this phenotype. We also show that the pattern of inheritance of HP is
      probably complex and that other genes may be involved in this genetic disease.

PMID- 10204853
TI  - Ring 22 duplication/deletion mosaicism: clinical, cytogenetic, and molecular
      characterisation.
AB  - A patient with several features consistent with duplication of 22q11.2 (cat eye
      syndrome or CES) was found to be mosaic for a dicentric double ring chromosome 22
      on postnatal karyotyping of peripheral blood. The initial karyotype was
      46,XX,r(22)(p12q13) [46]/46,XX,dic r(22)(p12q13; p12q13)[4]. The amount of
      material duplicated in the dic r(22) was determined to include and extend beyond
      the CES critical region into 22q13.3. However, karyotyping of lymphocytes and
      fibroblasts, at 27 and 13 months of age respectively, showed no dic r(22) present
      in any of the cells examined. We suggest that the CES features in this patient,
      and potentially in other ring cases with CES phenotypic features, might result
      from a high level of mosaicism for a dic r(22) during early fetal development.
      Usually this unstable dic r(22) is subsequently lost from most cells.

PMID- 10204854
TI  - Triplication of distal chromosome 10q.
AB  - We describe a patient with a de novo chromosomal aberration with karyotype
      46,XY,10q+, presenting clinical features of partial duplication of distal
      chromosome 10q. Further studies using microsatellites and FISH showed a
      triplication of distal chromosome 10q. The rearrangement involved both maternal
      homologues and the middle chromosomal 10q fragment of the triplication was
      inverted, similar to previously reported chromosomal triplications. Chromosomal
      triplications may be more frequent than assumed and may share a common molecular
      mechanism.

PMID- 10204855
TI  - Skin pigmentary anomalies and mosaicism for an acentric marker chromosome
      originating from 3q.
AB  - We report on a 22 year old man with hyperpigmentation distributed along the lines
      of Blaschko in whom cytogenetic analysis showed mosaicism for an unusual
      supernumerary marker chromosome. The patient was of normal intelligence and was
      not dysmorphic. The marker was present in 30% of his lymphocytes and in 6% of his
      skin fibroblasts from a dark area, while fibroblasts from a light area showed a
      normal karyotype, 46,XY. We have identified the origin of the marker using
      fluorescence in situ hybridisation (FISH) with whole chromosome painting probes
      and YAC specific clones. The marker was found to consist of duplicated chromosome
      material from the distal part of chromosome 3q and was interpreted as inv
      dup(3)(qter-->q27.1::q27.1-->qter). Hence, this marker did not include any known
      centromeric region and no alpha satellite DNA could be detected at the site of
      the primary constriction. The patient was therefore tetrasomic for 3q27-q29 in
      the cells containing the marker chromosome. We postulate that, in our case,
      pigmentary anomalies may result directly from the gain of specific pigmentation
      genes localised on chromosome 3q.

PMID- 10204856
TI  - Autosomal dominant optic atrophy with unilateral facial palsy: a new hereditary
      condition?
AB  - A mother and daughter are reported with bilateral optic atrophy with onset in
      infancy and unilateral facial palsy. This appears to be a novel autosomal
      dominant disorder.

PMID- 10204857
TI  - Monozygotic twin brothers with the fragile X syndrome: different CGG repeats and
      different mental capacities.
AB  - Little is known about the mechanism of CGG instability and the time frame of
      instability early in embryonic development in the fragile X syndrome. Discordant
      monozygotic twin brothers with the fragile X syndrome could give us insight into
      the time frame of the instability. We describe monochorionic diamniotic twin
      brothers with the fragile X syndrome who had different CGG repeats and different
      mental capacities, whereas the normal mother had a premutation. The more retarded
      brother had a full mutation in all his cells and no FMR-1 protein expression in
      lymphocytes, whereas the less retarded brother had 50%/50% mosaicism for a
      premutation and full mutation and FMR-1 protein expression in 26% of his
      lymphocytes. The differences in repeat size could have arisen either before or
      after the time of splitting. The time of splitting in this type of twin is around
      day 6-7. Given the high percentage of mosaicism, we hypothesise that the
      instability started before the time of splitting at day 6-7.

PMID- 10204858
TI  - Mendelian segregation of normal CAG trinucleotide repeat alleles at three
      autosomal loci.
AB  - Segregation ratio distortion (SRD) with preferential transmission of expanded CAG
      alleles has been reported in Machado-Joseph disease (MJD/SCA3), spinocerebellar
      ataxia type I (SCA1), and dentatorubral-pallidoluysian atrophy (DRPLA). We have
      examined the transmission frequencies of alleles in normal heterozygotes at these
      disease loci in 377 pairs of twins and their parents and find no evidence for
      SRD.

PMID- 10204859
TI  - Allele specific oligonucleotide analysis of the common deafness mutation 35delG
      in the connexin 26 (GJB2) gene.
AB  - Despite the large number of genes that are expected to be involved in non
      syndromal, recessive deafness, only a few have been cloned. One of these genes is
      GJB2, which encodes connexin 26. A frameshift mutation in this gene has been
      reported to be common in several populations and a carrier frequency of about 1
      in 30 people has been detected in Italy and Spain. Mutation 35delG is difficult
      to detect because it lies within a stretch of six guanines flanked by thymines,
      so the deletion of one G does not create or destroy a restriction site and
      mutagenesis primers are not useful for this mutation. We have generated an allele
      specific oligonucleotide method that uses 12-mer oligonucleotides and easily
      discriminates between the normal and 35delG alleles. The method should permit a
      rapid analysis of this mutation in congenital cases (recessive or sporadic),
      including diagnosis and carrier detection of 35delG in the population.

PMID- 10204860
TI  - BRCA1 expression is not affected by the intronic 12 bp duplication.

PMID- 10204861
TI  - First putative sequence alterations in the minimal CFTR promoter region.

PMID- 10204862
TI  - Improved contrast agent bolus tracking using T1 FARM.
AB  - Current MRI bolus tracking techniques, such as saturation recovery Turbo-FLASH
      (srTFL), suffer from signal saturation at high contrast concentrations. In this
      study T1 Fast Acquisition Relaxation Mapping (T1 FARM) was compared to srTFL. In
      phantoms, T1 FARM maps were linear with [Gd-DTPA] up to 7.0 mmol/L while srTFL
      images saturated above 2.0 mmol/L. In the canine left ventricle, blood
      concentration curves determined from T1 FARM saturated with bolus injections
      exceeding 0.075 mmol/kg, while srTFL curves saturated above 0.025 mmol/kg of Gd
      DTPA. Also, T1 FARM improved contrast-to-noise ratio in tissue concentration
      curves since higher contrast concentrations could be measured without saturating.

PMID- 10204863
TI  - Further evaluation of the initial negative response in functional magnetic
      resonance imaging.
AB  - The initial negative response (i.e., the dip) in the functional MR signal at
      stimulus onset has aroused much interest. Such a response is consistent with
      optical imaging data and can be potentially mapped to generate spatially more
      specific maps. However, there are still controversies regarding the exact origin
      of the initial response. In particular, experimental reports of its echo-time
      dependence have been inconsistent. Furthermore, several investigators have
      suggested the possibility of an apparent dip that may arise artifactually when
      the interstimulus interval (ISI) is not sufficiently long. The present study
      investigates the echo-time dependence of the initial response and the effect of
      the ISI on the initial response. Experimental results obtained at TEs of 21, 30,
      and 45 msec demonstrate that the initial dip has a TE dependence that is in
      agreement with a T2* contrast, and thereby consistent with a blood oxygenation
      level-dependent origin. At an ISI of 90 sec, a statistically significant initial
      negative response was detected and shown to be indistinguishable from that
      observed at an ISI of 45 sec, which was used in our previous studies, indicating
      that the initial negative response observed at 4 T is not a consequence of short
      ISI.

PMID- 10204864
TI  - Perfluorocarbon emulsions as intravenous delivery media for hyperpolarized xenon.
AB  - The use of perfluorooctyl bromide (PFOB) emulsions as delivery media for
      hyperpolarized xenon has been investigated. Emulsion droplet size was controlled
      by varying the content of egg yolk phospholipid (EYP), which served as an
      emulsifier. Hyperpolarized 129Xe nuclear magnetic resonance (NMR) spectra of the
      dissolved gas were obtained. The NMR spectra were found to be correlated strongly
      with the emulsion droplet size distribution. The NMR line width is determined by
      xenon exchange between the PFOB droplets and the aqueous environment. Our
      findings show that, in a 1.5-Tesla field, relatively narrow 129Xe NMR spectra are
      obtained for droplet sizes larger than 5 microm. Preliminary results on animal
      models show that PFOB emulsions have potential as hyperpolarized 129Xe carriers
      for in vivo magnetic resonance applications.

PMID- 10204865
TI  - Spectral quantitation by principal component analysis using complex singular
      value decomposition.
AB  - Principal component analysis (PCA) is a powerful method for quantitative analysis
      of nuclear magnetic resonance spectral data sets. It has the advantage of being
      model independent, making it well suited for the analysis of spectra with
      complicated or unknown line shapes. Previous applications of PCA have required
      that all spectra in a data set be in phase or have implemented iterative methods
      to analyze spectra that are not perfectly phased. However, improper phasing or
      imperfect convergence of the iterative methods has resulted in systematic errors
      in the estimation of peak areas with PCA. Presented here is a modified method of
      PCA, which utilizes complex singular value decomposition (SVD) to analyze
      spectral data sets with any amount of variation in spectral phase. The new method
      is shown to be completely insensitive to spectral phase. In the presence of
      noise, PCA with complex SVD yields a lower variation in the estimation of peak
      area than conventional PCA by a factor of approximately 2. The performance of the
      method is demonstrated with simulated data and in vivo 31P spectra from human
      skeletal muscle.

PMID- 10204867
TI  - Long-term effects of repetitive exposure to a static magnetic field (1.5 T) on
      proliferation of human fetal lung fibroblasts.
AB  - The aim of the study was to assess the effects of repetitive exposures to a
      static magnetic field (1.5 T) on human fetal lung fibroblast (HFL) proliferation.
      HFL were exposed three times a week for 1 hr to a static magnetic field for 3
      weeks. Cells were subcultured every week. Population doublings (PD) and
      cumulative population doublings (CPD) were calculated weekly. Colony formation
      assays, bromodeoxyuridine enzyme-linked immunosorbent assay, and cell cycle
      analysis were performed weekly. After the third week, proliferation kinetics were
      assessed. Over a period of 3 weeks no statistically significant differences
      between the PD and CPD of exposed and control cells could be detected. Clonogenic
      activity, DNA synthesis, cell cycle, and proliferation kinetics were not altered
      by magnetic field exposure. The data do not provide evidence that repetitive
      exposures to a static magnetic field (1.5 T) exert effects on HFL proliferation.

PMID- 10204866
TI  - Localized 15N NMR spectroscopy of rat brain by ISIS.
AB  - Three-dimensional image-selected in vivo spectroscopy (ISIS), combined with
      proton-decoupled nuclear-Overhauser-enhanced 15N nuclear magnetic resonance
      (NMR), was used to localize [15N]metabolites, observed by a head coil, to the
      brain in rats. In spontaneously breathing anesthetized rats given intravenous
      [15N]ammonium acetate infusion, brain [5-15N]glutamine was observed in the
      localized spectrum with a v1/2 of 5 Hz in 19-28 min at 4.7 T, while the signal
      from blood [15N]urea was eliminated by the localization process. In rats given
      [15N]leucine infusion, the peak representing predominantly (89%) brain
      [15N]glutamate was observed, with elimination of the signal from muscle
      [15N]alanine. In vivo peak areas of the brain [15N]metabolites in the localized
      spectra were proportional to their concentrations. The advantages and limitations
      of localization by ISIS using a volume coil with a homogeneous B1 field are
      compared with those of localization by a surface coil for in vivo 15N NMR study
      of neurotransmitters in the brain.

PMID- 10204868
TI  - Simultaneous recording of evoked potentials and T2*-weighted MR images during
      somatosensory stimulation of rat.
AB  - Somatosensory evoked potentials (SEP) and T2*-weighted nuclear magnetic resonance
      (NMR) images were recorded simultaneously during somatosensory stimulation of rat
      to investigate the relationship between electrical activation of the brain tissue
      and the signal intensity change in functional NMR imaging. Electrical forepaw
      stimulation was performed in Wistar rats anesthetized with alpha-chloralose. SEPs
      were recorded with calomel electrodes at stimulation frequencies of 1.5, 3, 4.5,
      and 6 Hz. At the same time, T2*-weighted imaging was performed, and the signal
      intensity increase during stimulation was correlated with the mean amplitude of
      the SEP. Both the stimulation-evoked signal intensity increase in T2*-weighted
      images and the amplitude of SEPs were dependent on the stimulation frequency,
      with the largest signals at a stimulation frequency of 1.5 Hz and decreasing
      activations with increasing frequencies. The feasibility of simultaneous,
      artifact-free recordings of T2*-weighted NMR images and of evoked potentials is
      proved. Furthermore, the study demonstrates-in the intact brain-the validity of
      functional magnetic resonance imaging for estimating the intensity of
      electrocortical activation.

PMID- 10204869
TI  - Radiofrequency power calibration for magnetic resonance imaging using signal
      phase as indicator.
AB  - A novel radiofrequency (rf) power calibration method for the purpose of nuclear
      magnetic resonance excitations based on monitoring signal phase rather than
      signal amplitude is described theoretically and is demonstrated experimentally.
      This unique method enables the determination of rf power required for any desired
      tip angle in clinical magnetic resonance imaging procedures with an accuracy of 1
      5%, essentially independent of motion, flow, slice variations, and/or T1 and T2
      variations. The advantages of the new method are discussed and are compared with
      currently common, amplitude-based calibration techniques.

PMID- 10204870
TI  - Early changes in water diffusion, perfusion, T1, and T2 during focal cerebral
      ischemia in the rat studied at 8.5 T.
AB  - The time evolution of water diffusion, perfusion, T1, and T2 is investigated at
      high magnetic field (8.5 T) following permanent middle cerebral artery occlusion
      in the rat. Cerebral blood flow maps were obtained using arterial spin tagging.
      Although the quantitative perfusion measurements in ischemic tissue still pose
      difficulties, the combined perfusion and diffusion data nevertheless distinguish
      between a "moderately affected area," with reduced perfusion but normal
      diffusion; and a "severely affected area," in which both perfusion and diffusion
      are significantly reduced. Two novel magnetic resonance imaging observations are
      reported, namely, a decrease in T2 and an increase in T1, both within the first
      few minutes of ischemia. The rapid initial decrease in T2 is believed to be
      associated with an increase in deoxyhemoglobin levels, while the initial increase
      in T1 may be related to several factors, such as flow effects, an alteration in
      tissue oxygenation, and changes in water environment.

PMID- 10204871
TI  - T1 measurements of 31P metabolites in resting and exercising human
      gastrocnemius/soleus muscle at 1.5 Tesla.
AB  - This study has measured the apparent 31P T1 times at 1.5 T in human
      gastrocnemius/soleus muscle groups at rest, during exercise, and during recovery
      from a 90-sec submaximal plantar flexion exercise. T1 times were measured with a
      10-sec time resolution in 11 normally active volunteers using a surface coil with
      a nine-point progressive saturation technique. A two-point short repetition time
      technique was also used. Both techniques showed similar trends in the apparent
      T11 times of all the 31P metabolites at rest, during exercise, and during
      recovery. For the nine-point progressive saturation technique, the apparent T1 of
      PCr and beta-ATP decreased approximately 20% to a steadystate value (P = 0.027
      and P = 0.004, respectively). The two-point short repetition time technique
      demonstrated a 10% reduction in the apparent T1 of PCr and beta-ATP Both
      techniques demonstrated an apparent T1 increase of 58% for inorganic phosphate at
      the beginning of exercise (P<0.0001) and a return to resting value during the 90
      sec submaximal isometric contraction. Neither technique showed any significant
      differences between resting and exercising T1 times of the alpha-ATP and gamma
      ATP resonances (P = 0.06 and P>0.40, respectively).

PMID- 10204872
TI  - T2 vertebral bone marrow changes after space flight.
AB  - Bone biopsies indicate that during immobilization bone marrow adipose tissue
      increases while the functional cellular fraction decreases. One objective of our
      Spacelab flight experiment was to determine, using in vivo volume-localized
      magnetic resonance spectroscopy (VLMRS), whether bone marrow composition was
      altered by space flight. Four crew members of a 17 day Spacelab mission
      participated in the experiment. The apparent cellular fraction and transverse
      relaxation time (T2) were determined twice before launch and at several times
      after flight. Immediately after flight, no significant change in the cellular
      fraction was found. However, the T2 of the cellular, but not the fat component
      increased following flight, although to a variable extent, in all crew members
      with a time course for return to baseline lasting several months. The T2 of seven
      control subjects showed no significant change. Although these observations may
      have several explanations, it is speculated that the observed T2 changes might
      reflect increased marrow osteoblastic activity during recovery from space flight.

PMID- 10204873
TI  - Analytical model of susceptibility-induced MR signal dephasing: effect of
      diffusion in a microvascular network.
AB  - A deterministic analytical model that describes the time course of magnetic
      resonance signal relaxation due to magnetic field inhomogeneity induced by a
      vascular network is developed. Both static and diffusion dephasing are taken into
      account. The contribution of the diffusion dephasing is calculated for relatively
      large vessels (R>10 microm) or short measurement times when the diffusion length
      is smaller than the vessel radius. The signal is found to possess the following
      features: a) an initial deviation from the monoexponential relaxation which is
      more pronounced for the imaginary part of the signal; b) a deviation from
      monoexponential relaxation at short echo times for the spin-echo (SE) signal
      measured as a function of the echo time; c) the echo maximum of the SE signal
      shifted from the nominal echo time to a shorter time; and d) a diffusion effect
      much stronger for the SE than for the free induction decay experiment. The model
      presented agrees within its validity domain with a known Monte Carlo simulation.

PMID- 10204875
TI  - MR phase-contrast flow measurement with limited spatial resolution in small
      vessels: value of model-based image analysis.
AB  - Magnetic resonance phase-contrast volume flow rate (VFR) measurement with limited
      resolution in small vessels is subject to two major sources of error: a) partial
      volume artifacts, causing systematic overestimation of the VFR, and b) errors
      related to the selection of vessel pixels [region of interest (ROI)], causing
      large inter-observer and intra-observer variability. Additionally, limited
      resolution results in Gibbs-ringing around vessels, which adversely affects VFR
      determination. In this paper, a semi-automatic model-based method is presented
      that effectively eliminates errors due to both partial volume effect and Gibbs
      ringing and also minimizes errors from variability in the ROI selection. The
      model assumes a parabolic flow profile and cylindrical vessel geometry,
      incorporates inflow effects, and takes into account the point-spread function of
      the acquisition. The method automatically estimates maximum velocity, vessel
      radius, and VFR. The method is validated in phantoms under various conditions and
      evaluated in vivo. For small vessels with moderately pulsatile flow, it is
      demonstrated that accurate VFRs and diameter estimates are obtained, virtually
      independent of the ROI selection, even in vessels covered by just a few pixels.
      Compared with conventional VFR analysis, both accuracy and reproducibility
      improve significantly.

PMID- 10204874
TI  - Measurement of human myocardial perfusion by double-gated flow alternating
      inversion recovery EPI.
AB  - This paper presents a flow-sensitive alternating inversion recovery (FAIR) method
      for measuring human myocardial perfusion at 1.5 T. Slice-selective/non-selective
      IR images were collected using a double-gated IR echoplanar imaging sequence.
      Myocardial perfusion was calculated after T1 fitting and extrapolation of the
      mean signal difference SI(Sel - SI(NSel). The accuracy of the method was tested
      in a porcine model using graded intravenous adenosine dose challenge. Comparison
      with radiolabeled microsphere measurements showed a good correlation (r = 0.84;
      mean error = 20%, n = 6) over the range of flows tested (0.9-7 ml/g/min). Applied
      in humans, this method allowed for the measurement of resting myocardial flow
      (1.04+/-0.37 ml/g/min, n = 11). The noise in our human measurements (SE(flow) =
      0.2 ml/g/min) appears to come primarily from residual respiratory motion.
      Although the current signal-to-noise ratio limits our ability to measure small
      fluctuations in resting flow accurately, the results indicate that this
      noninvasive method has great promise for the quantitative assessment of
      myocardial flow reserve in humans.

PMID- 10204876
TI  - Determination of 3D cartilage thickness data from MR imaging: computational
      method and reproducibility in the living.
AB  - The objective of this work was to develop a computational approach for
      quantifying the three-dimensional (3D) thickness distribution of articular
      cartilage with magnetic resonance (MR) imaging, independent of the imaging plane,
      and to test the reproducibility of the method in the living. An algorithm was
      implemented, based on a 3D Euclidean distance transformation, and its accuracy
      was assessed in geometric test objects, for which an analytic solution was
      available. The precision of the method was evaluated in six replicated MR data
      sets of the knee joint cartilage of eight volunteers. The algorithm produced 3D
      thickness values identical to those of the analytic solutions in the test
      objects. The reproducibility of the mean cartilage thickness in the patellar and
      tibial cartilages was 1.5-3.4% (root-mean-square average of the individual
      coefficient of variation percent), that of the maximal thickness 2.1-7.9%, and
      that of the thickness distribution 2.3-6.1%. The method presented allows for
      noninvasive analysis of 3D cartilage thickness from MR images in biomechanical
      and clinical investigations.

PMID- 10204877
TI  - Investigating the dependence of BOLD contrast on oxidative metabolism.
AB  - Most functional magnetic resonance imaging (fMRI) studies are based on measuring
      the changes in the blood oxygenation level-dependent (BOLD) contrast that arise
      from a complex interplay between cerebral hemodynamics and oxidative metabolism.
      To separate these effects, we consecutively applied two different stimuli: visual
      stimulation (black/white checkerboard alternating with a frequency of 8 Hz) and
      hypercapnia (inspiration of 5% CO2). Changes in cerebral blood flow (deltaCBF)
      and the effective transverse relaxation time (T2*) were measured in an
      interleaved manner by combining a previously described spin-labeling technique
      with BOLD-based fMRI. In six healthy volunteers, T2* was significantly longer
      during hypercapnia than during visual stimulation, whereas the corresponding
      deltaCBF values were the same at the given level of significance (P<0.01). This
      finding is explained by a significant increase in oxygen consumption under visual
      stimulation. The average T2* changes in the visual cortex related to cerebral
      hemodynamics and oxidative metabolism were 10.6+/-3.0% and -4.7+/-1.2%,
      respectively, resulting in a net increase of 5.9+/-2.3%. Although the hemodynamic
      effect is dominant, the increase in oxidative metabolism gives rise to a
      significant decrease in BOLD contrast. The calculated average change in the
      cerebral metabolic rate of oxygen (CMRO2), 4.4+/-1.1% (N = 6), is in excellent
      agreement with previous results obtained by positron emission tomography.

PMID- 10204878
TI  - Noninvasive determination of coronary blood flow velocity with magnetic resonance
      imaging: comparison of breath-hold and navigator techniques with intravascular
      ultrasound.
AB  - The aim of this study was to evaluate two different magnetic resonance (MR)
      techniques for the noninvasive assessment of intracoronary blood flow. Coronary
      blood flow velocities were measured invasively in 26 angiographically normal
      segments of 12 patients. Noninvasive measurements were performed in identical
      segments with two MR techniques using a 1.5 T MR tomograph (ACS NT, Philips). A
      single breath-hold technique (temporal resolution: 140 msec) and a similar non
      breath-hold technique with prospective navigator correction and improved temporal
      resolution (45 msec) were used. Maximal coronary flow velocities determined by MR
      correlated closely with invasive measurements (breath-hold: r = 0.70; navigator:
      r = 0.86); however, a significant underestimation of the MR measurements was
      found (slope = 0.33 and 0.37). The relative difference from the invasive method
      was lower for the navigator technique compared with the breath-hold technique
      (P<0.02). Both MR techniques allow the determination of coronary blood flow
      velocities. The higher temporal resolution and shorter acquisition window of
      navigator-corrected non-breath-hold techniques lead to increased accuracy. This
      approach is a further step toward the diagnostic use of MR flow measurements in
      coronary artery disease.

PMID- 10204879
TI  - The early response in fMRI: a modeling approach.
AB  - A mathematical model is presented to study the generation of the early response
      phenomenon in fMRI. Initially, we demonstrate that a simple combination of the
      changes taking place in cerebral blood volume and flow could create the transient
      early signal decrease, by analyzing their effects on total per voxel
      deoxyhemoglobin content. Also, we examine the traditional paradigm for the early
      response: that it may be caused by an early burst of oxidative metabolism and
      conclude that such changes also explain the early transient response. We suggest
      that the volume effect may play a role in the generation of the early response
      phenomenon along with an early upregulation of oxidative metabolism, and that
      this role may be important if the early response phenomenon is shown to occur at
      the level of the venous blood pool, and not just at the level of the capillary
      bed.

PMID- 10204880
TI  - 3D coronary artery imaging with phase reordering for improved scan efficiency.
AB  - Three-dimensional (3D) coronary imaging has the potential to overcome problems
      resulting from vessel tortuosity and to reduce partial volume effects. With these
      techniques, however, acquisition times are long and respiratory motion artifacts
      problematical. This work describes the development of a method that applies phase
      encode reordering to 3D acquisitions, allowing larger navigator acceptance
      windows to be used, with a consequent reduction in acquisition time. This method
      is compared with navigator acceptance window methods (the acceptance-rejection
      algorithm and the diminishing variance algorithm) and the retrospective
      respiratory gating technique, both in vitro and in vivo. The use of phase
      reordering with a 10 mm acceptance window provided a significant increase in scan
      efficiency over a non-reordered 5 mm method (P<0.001) with no significant change
      in image quality, and a significant increase in image quality compared with a non
      reordered image acquired in the same time (P<0.05). A significant improvement in
      both image quality and scan efficiency was demonstrated over the retrospective
      respiratory gating method (P<0.05).

PMID- 10204881
TI  - A strategy to optimize the signal-to-noise ratio in one-coil arterial spin
      tagging perfusion imaging.
AB  - The signal-to-noise ratio of the perfusion image (SNR(perfu)) in a spin-tagging
      experiment is shown to depend on both the degree of spin labeling (alpha) and the
      signal-to-noise ratio of the proton density images (SNRimage) used to calculate
      the perfusion image. When a single radiofrequency (RF) coil is used for both spin
      tagging and magnetic resonance (MR) imaging, magnetization transfer (MT) effects
      decrease SNRimage, and therefore SNRperfu, by an amount that depends on the
      strength B1 and offset deltaomega (determined by the gradient strength G(I)
      applied during spin tagging) of the labeling RF pulse. It is shown that by
      optimizing B1 and G(I), it is possible to reduce MT effects and thus increase
      SNRimage, while leaving alpha unchanged. As a result, SNRperfu, will be improved.
      An equation for calculating perfusion under general conditions of such reduced MT
      effects is derived and shown to give perfusion rates that are independent of the
      strength and offset of the labeling RF irradiation.

PMID- 10204882
TI  - Switchable multicoil array for MR micro-imaging of breast lesions.
AB  - High-resolution breast imaging may improve differentiation between benign and
      malignant lesions and may be important for refining treatment strategy. This
      article presents a new, flexible design of a breast-imaging coil capable of
      providing breast images of a high level of spatial resolution. Referred to as a
      switchable coil array, the design uses small-diameter surface coils that provide
      high sensitivity of detection, which, combined with a relatively small field of
      view, affords a high degree of spatial resolution (up to 200 microm). Remote
      selection of the coil pair closest to the position of the lesion in the breast
      permits coverage of the whole breast without changing the position of the coils
      or the patient. High-resolution MR images of phantom and volunteer patients with
      benign and malignant breast lesions are presented.

PMID- 10204883
TI  - Voxel sensitivity function description of flow-induced signal loss in MR imaging:
      implications for black-blood MR angiography with turbo spin-echo sequences.
AB  - The conditions in which the image intensity of vessels transporting laminar flow
      is attenuated in black-blood MR angiography (BB-MRA) with turbo spin-echo (TSE)
      and conventional spin-echo (CSE) pulse sequences are investigated experimentally
      with a flow phantom, studied theoretically by means of a Bloch equation-voxel
      sensitivity function (VSF) formalism, and computer modeled. The experiments
      studied the effects of: a) flow velocity, b) imaging axes orientation relative to
      the flow direction, and c) phase encoding order of the TSE train. The formulated
      Bloch equation-VSF theory describes flow effects in two-dimensional (2D)- and 3D
      Fourier transform magnetic resonance imaging. In this theoretical framework, the
      main attenuation mechanism instrumental to BB-MRA, i.e., transverse magnetization
      dephasing caused by flow in the presence of the imaging gradients, is described
      in terms of flow-induced distortions of the individual voxel sensitivity
      functions. The computer simulations predict that the intraluminal homogeneity and
      extent of flow-induced image intensity attenuation increase as a function of
      decreasing vessel diameter, in support of the superior image quality achieved
      with TSE-based BB-MRA in the brain.

PMID- 10204884
TI  - Ultra-short echo-time 2D time-of-flight MR angiography using a half-pulse
      excitation.
AB  - Flow-related artifacts remain a significant concern for magnetic resonance (MR)
      angiography because their appearance in angiograms adversely impacts accuracy in
      evaluation of arterial stenoses. In this paper, a half-pulse excitation scheme
      for improved two-dimensional time-of-flight (2D TOF) angiography is described.
      The proposed method eliminates the need for gradient moment nulling (of all
      orders), providing significant reductions in spin dephasing and consequent
      artifactual signal loss. Furthermore, because the post-excitation refocusing and
      flow compensation gradients are obviated, the achievable echo time is
      dramatically shortened. The half-pulse excitation is employed in conjunction with
      a fast radial-line acquisition, allowing ultra-short echo times on the order of
      250-300 microsec. Radial-line acquisition methods also provide additional
      benefits for flow imaging: effective mitigation of pulsatile flow artifacts, full
      k-space coverage, and decreased scan times. The half-pulse excitation/radial-line
      sequence demonstrated improved performance in initial clinical evaluations of the
      carotid bifurcation when compared with a conventional 2D TOF sequence.

PMID- 10204885
TI  - Analytic approach to the design of transverse gradient coils with co-axial return
      paths.
AB  - Transverse gradient coils with co-axial return paths offer reduced acoustic noise
      compared with standard cylindrical gradient coils, due to local force balancing,
      and can also easily be made to have a length to diameter ratio that is less than
      one. Analytic expressions for the magnetic field and vector potential generated
      by this type of coil are described here, along with a formula for calculating the
      coil inductance. It is shown that these expressions allow the implementation of
      powerful analytic methods of coil design, as well as the incorporation of active
      magnetic screening. It is also demonstrated how the mathematics specifies the
      best parameters to use when designing coils with small numbers of elements. A
      head gradient coil for use at 3.0 T has been designed using the analytic approach
      described here. The process of coil design and construction is outlined and the
      performance of the coil in comparison with a similar standard cylindrical coil is
      described.

PMID- 10204886
TI  - Segmented k-space fast cardiac imaging using an echo-train readout.
AB  - A segmented k-space fast gradient-echo pulse sequence with an echo-train readout
      (FGRE-ET) was developed for high-quality cine imaging of the heart in reduced
      scan times. Using segmented FGRE-ET, cine images of the heart can be acquired in
      as few as 1-5 heart beats and do not display the geometric distortion and flow
      related artifacts typically associated with cardiac echoplanar imaging (EPI).
      Segmented FGRE-ET was compared with conventional segmented FGRE and with
      conventional multi-phase EPI in normal volunteers. Segmented FGRE-ET was found to
      have reduced temporal blurring compared with segmented FGRE for cine imaging in 4
      heart beats (P<0.05). Also, segmented FGRE-ET did not display geometric
      distortion characteristic of conventional EPI (P<0.05). Segmented FGRE-ET may be
      particularly applicable to functional cardiac stress testing because it allows
      versatile cine imaging in very short breath-holds.

PMID- 10204887
TI  - Parameter estimation from Rician-distributed data sets using a maximum likelihood
      estimator: application to T1 and perfusion measurements.
AB  - General expressions are presented to calculate the maximum likelihood (ML)
      estimator and corresponding Fisher matrix for Rician-distributed data sets. This
      estimator results in the most precise, unbiased estimations of T1 from magnitude
      data sets, even when low signal-to-noise ratios (<6) are present. By optimizing
      the sample point distributions for inversion-recovery experiments, a 32% increase
      in precision of the estimated T1 is obtained, compared with a linear sampling
      scheme. Perfusion rates are estimated from combined data sets of the slice- and
      nonslice-selective inversion-recovery experiments, as obtained with the flow
      sensitive alternating inversion recovery (FAIR) technique. The ML estimator for
      the combined data set results in the most precise, unbiased estimations of the
      perfusion rate. Error analysis shows that very high signal-to-noise ratios are
      required for precise estimation of perfusion rates from FAIR experiments.

PMID- 10204888
TI  - Evidence for bi-exponential transverse relaxation of lactate in excised rat
      muscle.
AB  - To elucidate the low proton nuclear magnetic resonance (NMR) visibility of muscle
      lactate previously demonstrated in excised rat muscle, lactate transverse
      relaxation was investigated in the same model using double quantum editing
      sequences with effective echo times ranging from 55 to 475 msec. On this time
      scale, muscle lactate clearly exhibits a bi-exponential transverse relaxation
      with a short T2 of 33+/-5 msec (mean +/- SE, n = 3) and a long T2 of 230+/-10
      msec. The relative populations (84+/-4% vs. 16+/-4%, respectively) of these two
      lactate pools are compatible with compartmentation between intra- and
      extracellular muscle lactate.

PMID- 10204889
TI  - Magnetic resonance imaging of frozen tissues: temperature-dependent MR signal
      characteristics and relevance for MR monitoring of cryosurgery.
AB  - Previously, the magnetic resonance (MR) imaging appearance of frozen tissues
      created during cryosurgery has been described as a signal void. In this work,
      very short echo times (1.2 msec) allowed MR signals from frozen tissues to be
      measured at temperatures down to -35 degrees C. Ex vivo bovine liver, muscle,
      adipose tissue, and water were imaged at steady-state temperatures from -78
      degrees to +6 degrees C. Signal intensity, T2*, and T1 were measured using
      gradient-echo imaging. Signal intensity and T2* decrease monotonically with
      temperature. In the future, these MR parameters may be useful for mapping
      temperatures during cryosurgery.

PMID- 10204890
TI  - Wavelet packet denoising of magnetic resonance images: importance of Rician noise
      at low SNR.
AB  - Wavelet packet analysis is a mathematical transformation that can be used to post
      process images, for example, to remove image noise ("denoising"). At a very low
      signal-to-noise ratio (SNR <5), standard magnitude magnetic resonance images have
      skewed Rician noise statistics that degrade denoising performance. Since the
      quadrature images have approximately Gaussian noise, it was postulated that
      denoising would produce better contrast and sharper edges if performed before
      magnitude image formation. Signal-to-noise ratio (SNR), contrast-to-noise ratio
      (CNR), and edge blurring effects of these two approaches were examined in
      synthetic, phantom, and human MR images. While magnitude and complex denoising
      both significantly improved SNR and CNR, complex denoising yielded sharper edges
      and better low-intensity feature contrast.

PMID- 10204891
TI  - Twisted-pair RF coil suitable for locating the track of a catheter.
AB  - An RF coil, made by twisting a conventional wire loop, was tuned to form an
      extended sensor to provide an effective method of showing the track of a
      catheter. A twisted-pair coil can be made small enough in diameter to pass
      through needles in common clinical use. The coil has a very small field of view
      and in transmit/receive operation has minimal effect on the magnetization of the
      surrounding tissue.

PMID- 10204892
TI  - Toward high-resolution myocardial tagging.
AB  - Magnetic resonance imaging with preceding tissue tagging is a robust method for
      assessing cardiac motion of the entire heartbeat cycle with a high degree of
      accuracy. One limitation of this technique, however, is the low resolution of the
      obtained displacement map of the labeled points within the myocardium. By a new
      tagging technique, which is based on the combination of two or more measurements
      of the same slice but with different grid positions, a highly improved resolution
      of cardiac motion data can be achieved. In combination with a multi-heart-phase
      echo-planar imaging sequence, such images with doubled grid frequency can be
      acquired in two short breath-hold periods.

PMID- 10204893
TI  - Central hyperalgesic effects of noxious stimulation associated with the use of
      tourniquets.

PMID- 10204894
TI  - An investigation of the neurophysiologic mechanisms of tourniquet-related pain:
      changes in spontaneous activity and receptive field size in spinal dorsal horn
      neurons.
AB  - BACKGROUND AND OBJECTIVES: Several theories have been proposed for the pain
      resulting from the nerve compression and ischemia associated with maintaining the
      inflation of a pneumatic tourniquet on an extremity. This investigation observes
      changes in the spontaneous activity and receptive field (RF) size of spinal
      dorsal horn neurons during tourniquet-related nerve compression and ischemia.
      METHODS: Forty-eight pentobarbital-anesthetized rats were prepared for single
      unit spinal dorsal horn cell recording utilizing an in vivo extracellular
      technique. Cells were characterized as either low threshold mechanoreceptor (LTM)
      neurons, wide dynamic range (WDR) neurons, or high threshold nociresponsive (NR)
      neurons based on their response to light touch (brush), non-noxious pressure, or
      noxious pinch. Receptive fields were carefully mapped. A 1 x 9 cm pneumatic
      tourniquet (Hokanson, Inc., Seattle, WA) was then applied to the animals' hind
      limb thigh and inflated to 300 mm Hg for 60 minutes. Throughout the 60-minute
      tourniquet inflation period, spontaneous activity, cell firing rate response
      characteristics, and RF size were carefully monitored. RESULTS: Twenty-three
      cells in 20 animals were characterized and monitored: 8 LTM, 6 WDR, and 9 NR
      neurons. Receptive fields were distal to the tourniquet cuff for 16 cells and
      proximal for 7 cells. Low threshold mechanoreceptor neurons demonstrated little
      spontaneous activity prior to tourniquet inflation in the absence of RF
      stimulation. The RF size for all LTM neurons decreased or became silent during
      the tourniquet inflation period. The RF size increased in two of six WDR neurons
      with two cells demonstrating a progressive increase in intermittent spontaneous
      firing during the tourniquet inflation period. Receptive field size increased in
      five of five NR neurons with RF located proximal to the tourniquet cuff from 29
      +/- 10 mm2 to 54 +/- 30 mm2 (RF area 1.9 +/- 0.7; t = 2.7, P = .03). All five of
      these NR neurons also demonstrated an increase in spontaneous activity at 37 +/-
      14 minutes of tourniquet inflation which continued throughout the remainder of
      the tourniquet inflation period (P < .05). CONCLUSIONS: The results of this study
      indicate that nerve compression and ischemia results in block of input to LTM
      neurons having RFs distal to the tourniquet cuff and an increase in spontaneous
      activity and expansion of the RFs of NRs, especially those with RFs located
      proximal to the tourniquet. Increases in spontaneous firing activity and
      expansion of the RFs of nociresponsive dorsal horn neurons receiving input from
      primary afferent nociceptors proximal to the tourniquet may explain, in part, the
      neurophysiologic mechanism of tourniquet-related pain.

PMID- 10204895
TI  - Continuous spinal anesthesia: a comparative study of standard microcatheter and
      Spinocath.
AB  - BACKGROUND AND OBJECTIVES: This prospective, randomized study evaluated the
      advantages and disadvantages of a new subarachnoid catheter. METHODS: Sixty ASA I
      IV patients aged 40-70 years, scheduled for total knee arthroplasty, were
      randomly distributed into group 1 (Spinocath; Braun Melsungen, Germany) and group
      2 (Intralong; Pajunk, Germany). The study tabulated details of subarachnoid
      catheter insertion, dural puncture, time to free cerebrospinal fluid (CSF) flow,
      anesthesia onset time, surgery anesthesia time, the upper level of sensory block
      reached, the anesthesiologist-evaluated degree of difficulty with the technique,
      and the quality of analgesia obtained and complications. At the end of surgery,
      all the catheters were removed, and their patency was checked. RESULTS: Spinocath
      insertion required 6.3 +/- 3.2 minutes in group 1 versus 3.9 +/- 1.2 minutes in
      group 2 (P < .01) with similar difficulties with catheter introduction.
      Perception of dural puncture was better in group 1 (P < .05). There were
      significant intergroup differences in time to free flow of CSF through the
      catheter. In group 2, correct catheter positioning had to be confirmed by
      aspiration in 80% of cases (P < .05). At the end of surgery, the catheters were
      removed, and there were no significant differences between groups. The anesthetic
      blocks were similar with both systems. Patient opinion of the technique did not
      differ between groups, and regression analysis did not show any differences
      between groups or correlation to any incident during performance of the
      technique. Globally, the anesthesiologists participating in the study considered
      both systems to be easy to use and adequate for continuous spinal anesthesia.
      With respect to the advantage afforded by a directional needle in orientating the
      catheter within the spinal canal, the Spinocath system-with a longer technique
      performance time than the standard approach-involves a success rate and incidence
      of technical problems similar to that of the conventional technique.

PMID- 10204896
TI  - The safety and efficacy of combined spinal and epidural analgesia/anesthesia
      (6,002 blocks) in a community hospital.
AB  - BACKGROUND AND OBJECTIVES: This study examined the safety and efficacy of
      combined spinal and epidural (CSE) analgesia/anesthesia performed in a community
      hospital. METHODS: Labor and Surgical Anesthesia Quality Assessment Worksheets
      were completed by the responsible anesthesiologist for 7,893 general anesthetics
      and 7,931 regional anesthetics from January 1, 1994 to December 31, 1997. A
      retrospective computerized analysis of these data tabulated the number of
      regional anesthesia techniques and identified anesthesia effectiveness and
      complications associated with these procedures. The safety and efficacy of CSE
      analgesia/anesthesia (6,002 blocks) was assessed by comparing these results with
      reported complications and failure rates for spinal and epidural anesthesia.
      RESULTS: The CSE technique did not increase the risk of anesthesia complications,
      as compared with the reported prevalence associated with major regional
      anesthesia. It provided decreased failure rates for labor analgesia and
      comparable or decreased failure rates for surgical anesthesia, when compared with
      reported failure rates for epidural anesthesia. Apnea did not occur in
      parturients who received 4,164 CSE blocks with intrathecal sufentanil (ITS; 10,
      15, or 20 microg) for labor pain relief. However, the prevalence of laboring
      patients requiring intravenous medication for side effects was related to the
      dose of ITS: 10 microg (1.1%), 15 microg (4.6%), and 20 microg (5.5%) (P < .001).
      Patients who received prior systemic narcotics less than 6 hours before ITS were
      twice as likely to require intravenous treatment for low oxygen
      saturation/drowsiness (21%) than were those who experienced dysphagia or pruritus
      (10%) (P < .001). CONCLUSIONS: This review of 6,002 CSE blocks performed in a
      community hospital has demonstrated that CSE labor analgesia, surgical anesthesia
      are safe and efficacious. We believe that patient observation and continuous
      pulse oximetry for 1-2 hours after administration of ITS and prompt treatment
      with intravenous naloxone for severe drowsiness, low oxygen saturation (PaO2 <
      90% unresponsive to mask oxygen), or dysphagia should be used to minimize the
      risk of apnea.

PMID- 10204897
TI  - The performance of spinal anesthesia is marginally more difficult in the elderly.
AB  - BACKGROUND AND OBJECTIVES: We sought to determine if spinal anesthesia is more
      difficult to perform in the elderly. METHODS: All spinal anesthetics administered
      over 18 months by 18 anesthesiologists were eligible. We excluded anesthetics for
      hip fractures and cesarean deliveries. We recorded time to completion, number of
      spinal needles used, and number of approaches. The patients were prospectively
      divided into three age categories: patients <50 years of age (group 1); 50-70
      years of age (group 2); and >70 years of age (group 3). Descriptive statistics
      and chi-square test were performed. RESULTS: Nine hundred and ninety-nine
      anesthetics were analyzed. There were 368, 336, and 295 entries in groups 1, 2,
      and 3, respectively. Although the mean +/- SD (in min) times to accomplish the
      spinal technique were not significantly different (4.3 +/- 4.1, 4.4 +/- 3.2, and
      4.6 +/- 3.4 for groups 1, 2, and 3), there was a statistically greater frequency
      of more than one spinal needle used and more than one approach needed in the
      elderly. CONCLUSIONS: We conclude that patient age is a minor independent
      predictor of increased technical difficulty with spinal anesthesia.

PMID- 10204898
TI  - Comparison of 0.5% articaine and 0.5% prilocaine in intravenous regional
      anesthesia of the arm: a cross-over study in volunteers.
AB  - BACKGROUND AND OBJECTIVES: Earlier studies of the use of articaine in intravenous
      regional anesthesia (IVRA) are conflicting. In fact, despite similar
      physicochemical properties and regional anesthetic action, significant
      differences between articaine and prilocaine in IVRA have been reported.
      Articaine, being a potent local anesthetic with low degree of toxicity and being
      rapidly metabolized by esterases, could be a useful local anesthetic particularly
      in IVRA and, perhaps, could challenge prilocaine, the present local anesthetic of
      choice for this technique. METHODS: A double-blind, cross-over study of IVRA of
      the upper extremity in 10 healthy volunteers was performed. There was at least a
      1-week interval between the use of the two anesthetics in each volunteer. After
      exsanguination with an Esmarch bandage, IVRA was induced either with preservative
      free 0.5% articaine (5% Ultracaine, Hoechst, Germany, diluted with 0.9% NaCl) or
      0.5% prilocaine (Citanest, Astra, Sodertalje, Sweden) (35-50 mL, according to
      weight), injected in 2 minutes. Sensation at defined skin spots that were
      innervated by the median, musculocutaneous, radial, and ulnar nerves was tested
      by pinprick; motor function was tested by the movements of the wrist. After 20
      minutes, the tourniquet cuff was deflated in one step. Circulatory, toxic, and
      skin reactions were registered. At least 1 week after the second IVRA
      intracutaneous allergy testing with 0.5% articaine, 0.5% prilocaine, histamine,
      and saline was performed. RESULTS: There were no significant differences between
      the two local anesthetics in the onset of analgesia or anesthesia, degree of
      motor block, and recovery of IVRA. Onset of analgesia occurred 4.2-5.6 minutes,
      on average, after the injection. One volunteer had short-lasting tinnitus after
      tourniquet cuff deflation when prilocaine was used. Erythematous nonitching skin
      rashes developed in 8 of 10 volunteers when articaine was used, and two
      volunteers had rashes when prilocaine was used. These rashes disappeared within
      an hour, and negative intracutaneous test results confirmed their nonallergic
      origin. CONCLUSION: Both 0.5% articaine and 0.5% prilocaine, in a median dose of
      40 mL in adults, injected in 2 minutes, are effective and equipotent local
      anesthetics in IVRA of the arm. An earlier reported four-time faster onset time
      of the block by articaine in comparison with prilocaine may be caused by a very
      rapid injection rate (40 mL/30 sec) by the investigators of that study. The
      erythematous skin rashes after IVRA, in particular when articaine was used, may
      be a sign of venous endothelial irritation.

PMID- 10204899
TI  - Ropivacaine 0.25% and 0.5%, but not 0.125%, provide effective wound infiltration
      analgesia after outpatient hernia repair, but with sustained plasma drug levels.
AB  - BACKGROUND AND OBJECTIVES: Ropivacaine is a long-acting local anesthetic similar
      to bupivacaine, but with lower cardiac toxicity and intrinsic vasoconstrictive
      properties that may reduce the risk and extent of systemic plasma absorption.
      Plasma levels and risks are associated with the total dose used and the extent of
      absorption, with lower doses potentially representing less risk. Although both
      0.5% and 0.75% ropivacaine provide adequate analgesia for wound infiltration
      after hernia repair, the efficacy of lower doses and the early systemic
      absorption have not been reported. METHODS: We studied postoperative pain and
      systemic plasma levels following either the injection of 30 mL of saline or
      0.125%, 0.25%, or 0.5% ropivacaine into the wounds in 110 healthy patients
      following hernia repair under spinal anesthesia. Pain was assessed using visual
      analog scale (VAS) scores and algometer readings at rest and after coughing, and
      oral analgesic requirements were assessed in the first 5 hours after surgery and
      for the week after discharge. RESULTS: Both 0.25% and 0.5% ropivacaine provided
      pain relief following surgery when compared with saline or 0.125%. No adverse
      reactions to the drug were reported in any group. Plasma levels of ropivacaine
      peaked between 30 and 60 minutes, at 0.109, 0.249, and 0.399 mg/L for 0.125%,
      0.25%, and 0.5% concentrations, respectively. Although the levels were below
      those producing clinical symptoms, they remained elevated for the entire 2-hour
      sampling period. This implies an absorption-dependent elimination which is
      substantially longer than reported with other routes of injection. CONCLUSIONS:
      Ropivacaine 0.25% and 0.5% is adequate for pain relief after outpatient hernia
      repair, whereas the 0.125% solution is no more effective than saline. Prolonged
      systemic absorption from peripheral injection may be associated with prolonged
      elevations of plasma concentrations, which potentially could be associated with
      unexpectedly high plasma levels if repeated injections are performed in the
      perioperative period with higher concentrations or doses.

PMID- 10204900
TI  - Evaluation of peripheral morphine analgesia for lumpectomy and axillary node
      dissection: a randomized, double-blind, placebo-controlled study.
AB  - BACKGROUND AND OBJECTIVES: Morphine may elicit potent antinociceptive effects by
      binding and activating peripheral opioid receptors. However, the results in
      clinical studies have varied. We examined the postoperative analgesic effects of
      incisional morphine in patients undergoing lumpectomies and axillary node
      dissections for breast cancer. For this purpose, a concentration of morphine
      within the range (0.25-0.6%) of those utilized in previous studies for
      postarthroscopy analgesia was chosen (0.6%). METHODS: Forty-five patients
      scheduled to undergo a lumpectomy and axillary node dissections for breast cancer
      were enrolled in this study after receiving Ethics Committee approval and patient
      consent. Patients were randomized to undergo irrigation of the surgical sites for
      5 minutes prior to skin closure with 6 mg morphine diluted in 100 mL 0.9% normal
      saline (NS) and placebo intramuscular (i.m.) (peripheral MS group), 100 mL of
      0.9% NS alone and placebo i.m. (placebo group), or 100 mL of 0.9% NS and 6 mg
      morphine i.m. in the deltoid muscle (i.m. MS group) in a double-blind fashion. In
      the postanesthesia care unit, patients received fentanyl via a patient-controlled
      analgesia (PCA) device programmed to deliver 25 microg every 10 minutes to a
      maximum dose of 150 microg/h. Patients were evaluated for pain using a visual
      analog scale card from 0-10, opioid consumption, and incidences of side effects
      at 2, 6, 12, 18, and 24 hours after surgery. RESULTS: All patients had adequate
      analgesia at rest and during arm movement with visual analog pain scores (VAPS)
      <3/10 throughout the study period. There were no significant differences in
      demographics, total fentanyl consumption (500 vs. 475 vs 933 microg,
      respectively; P = .2), VAPS at rest and during arm movement as well as fentanyl
      consumption at the different evaluation points among the three groups.
      CONCLUSIONS: These results suggest that under the conditions of the study
      protocol, there is no value in utilizing morphine in solution at the surgical
      site for postoperative lumpectomy and axillary node dissection analgesia.

PMID- 10204901
TI  - Subarachnoid ketamine in swine--pathological findings after repeated doses: acute
      toxicity study.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study was to investigate whether
      5% ketamine with and without preservative, administered intrathecally to swine,
      produced a clinical anesthetic effect and caused direct subacute neurotoxicity.
      METHODS: Twenty pigs were used. Under general anesthesia, a subarachnoid catheter
      was placed at L5-L6 or L6-S1 spinal interspace. Five animals were used for
      initial clinical evaluation of the anesthetic effects of subarachnoid ketamine
      (12.5 and 25.0, and 500 mg). Two animals were excluded because of bloody taps,
      two served as controls (catheterization without drug administration), four
      received ketamine racemate (25.0 mg/d), four received ketamine racemate
      preservative free (25.0 mg/d), and three received benzethonium chloride, the
      ketamine excipient (0.05 mg/d). All drugs were administered for 7 days. The
      catheters were withdrawn at the end of the treatment period. After 35 days, the
      pigs were euthanized and the spinal cord removed and preserved for
      histopathologic study with hematoxilyn-eosin and luxol-fast blue myelin staining.
      Histopathologic effects were defined as absent/minimal, mild, or severe by a
      pathologist, unaware of group allocation, by evaluating the presence and
      intensity of peripheral and/or central chromatolysis, spongiosis, neuronal loss,
      perivascular neuroglia, neuronolysis, and myelin degeneration. RESULTS: All doses
      of ketamine produced immediate cutaneous anesthesia and motor block; benzethonium
      chloride did not. Histopathologic examination showed no neurotoxic effect of
      ketamine without preservative; ketamine with preservative showed a discrete
      neurotoxic effect, and the preservative alone produced a moderate neurotoxic
      effect. CONCLUSIONS: Clinically, in swine, subarachnoid ketamine without
      preservative is a safe and effective anesthetic and did not show significant
      neurotoxic effects. However, ketamine with preservative produces minimal changes,
      and benzethonium chloride alone produces moderate neurotoxic effects.

PMID- 10204902
TI  - The association between injected volume of local anesthetic and spread of
      epidural anesthesia: a hypothesis.
AB  - BACKGROUND AND OBJECTIVES: Clinically, an increase of the injected volume of
      local anesthetic does not result in a linear increase in the spread of epidural
      anesthesia. This study was designed to evaluate this observation. METHODS: One
      hundred twenty adult women undergoing abdominal gynecologic surgery were randomly
      assigned into 6 groups of 20 patients each. An epidural catheter was inserted in
      each patient via the L1-L2 interspace, and 2, 4, 6, 8, 10, and 12 mL of 2%
      mepivacaine was injected, respectively, in each group. Fifteen minutes later, the
      cephalad extent of hypesthesia above the second sacral dermatome was tested with
      an alcohol swab. RESULTS: The regression analysis between injected volume (x mL)
      and number of anesthetized dermatomes (y) approximates a cubic polynominal
      equation rather than a simple equation, as follows; y = 3.021 x - 0.274 x2 +
      0.009673 x3 (R2 = 0.938, P = .0435). CONCLUSIONS: The present study demonstrates
      lack of a linear relationship between injected volume of local anesthetic and
      spread of epidural anesthesia. Whether the cubic equation developed is clinically
      useful remains unclear because of the variability of the data.

PMID- 10204903
TI  - The effect of anesthetic patient education on preoperative patient anxiety.
AB  - BACKGROUND AND OBJECTIVES: Preoperative time spent with patients has been
      abbreviated with the advent of same-day admission requirements and outpatient
      surgery. This study was conducted to evaluate the effects that materials mailed
      to the home relating to anesthetic-focused patient education may have on
      preoperative patient anxiety. METHODS: Patients scheduled for a total hip
      arthroplasty or for a total knee arthroplasty were screened via telephone for
      inclusion in a prospective, randomized study. Patients were asked about their
      access to a video cassette recorder/player (VCR) and their limitations regarding
      hearing or vision. Subjects were randomly assigned to either the intervention
      group and received two pamphlets and a video describing general and regional
      anesthesia or to the usual care group. All subjects were mailed a preoperative
      demographic questionnaire and a State Trait Anxiety Inventory (STAI), as
      developed by CD Spielberger. Questionnaires were completed at least 96 hours
      prior to admission and again preoperative on the day of surgery. RESULTS: Of 236
      patients screened, 26 had no access to a VCR, 6 were hearing or visually
      impaired, and 4 declined participation. Of 200 subjects randomized, 134 completed
      both sets of questionnaires and thus form the basis of this report. A
      statistically significant difference between the subjects who received the video
      and pamphlets and the usual care subjects was detected with respect to change in
      STAI-assessed anxiety from baseline to immediately prior to surgery (P = .035).
      The intervention subjects experienced a smaller mean increase in anxiety. Forty
      nine percent of the usual care subjects expressed interest in having additional
      information. CONCLUSIONS: Increase in preoperative anxiety is diminished when
      additional anesthesia information in printed and video format is made available.
      Useful information can be provided to patients to view or read prior to surgery.

PMID- 10204904
TI  - Evaluation of the analgesic efficacy of EMLA cream in volunteers with differing
      skin pigmentation undergoing venipuncture.
AB  - BACKGROUND AND OBJECTIVES: Lidocaine/prilocaine cream (EMLA) applied to intact
      skin for 60 minutes has been shown to reduce venipuncture pain. Recent studies
      have suggested that lidocaine/prilocaine cream is less effective on heavily
      pigmented skin. The objective of this study was to evaluate the topical
      anesthetic efficacy of lidocaine/prilocaine cream in volunteers with varying skin
      pigmentation types. METHODS: Sixty volunteers were enrolled into each of three
      groups based on skin pigmentation history. Subjects were randomized to receive
      lidocaine/prilocaine cream onto the antecubital fossa of one arm and placebo
      cream on the comparable location of the other arm for either 60, 90, or 120
      minutes prior to venipuncture. Assessments of perceived pain associated with each
      venipuncture were made by the subject using a visual analog scale. RESULTS:
      Lidocaine/prilocaine cream applied for 60 minutes significantly (P < .0001)
      reduced the pain of venipuncture compared to placebo regardless of the skin
      pigmentation type. Pain reduction did not differ significantly across skin types
      (P = .7986). Additional exposure up to 120 minutes did not change the efficacy of
      EMLA cream. CONCLUSIONS: Lidocaine/prilocaine cream is a safe and effective
      topical anesthetic for reducing pain associated with venipuncture in individuals,
      regardless of skin pigmentation.

PMID- 10204905
TI  - Acute herpetic neuralgia and postherpetic neuralgia in the head and neck:
      response to gabapentin in five cases.
AB  - BACKGROUND AND OBJECTIVES: The clinical presentations and pharmacologic
      management of three patients with acute herpetic neuralgia (AHN) and two patients
      with postherpetic neuralgia (PHN), confined to the head and neck region, are
      described. METHODS: Two patients had pain in the ophthalmic division of the
      trigeminal nerve, two had pain confined to the C2-C4 dermatomes, and one patient
      had C2 pain with radiating and referred pain to the second and third divisions of
      the trigeminal nerve. RESULTS: Gabapentin, an anticonvulsant drug, was effective
      in treating these patients, including the two cases of AHN. All patients reported
      complete pain relief after titration with gabapentin up to 1,800 mg/d. The
      patients noted a dose-dependent decrease in pain almost immediately after
      starting gabapentin. Specifically, reduction in the frequency and intensity of
      allodynia, burning pain, shooting pain, and throbbing pain were noted. None of
      the patients experienced side effects from the drug. CONCLUSIONS: In view of the
      results in these patients, blinded, controlled studies are needed to determine
      the efficacy of gabapentin for treating AHN and PHN.

PMID- 10204906
TI  - Anxiety, vocalization, and agitation following peripheral nerve block with
      ropivacaine.
AB  - BACKGROUND AND OBJECTIVES: Central nervous system (CNS) and cardiovascular
      toxicity are potential side effects of local anesthetics. However, ropivacaine
      has been reported to be less CNS toxic than bupivacaine in human volunteers.
      METHODS: We describe three cases of peripheral nerve blockade with ropivacaine
      that resulted in unusual symptoms of CNS toxicity. RESULTS: In three patients,
      unexpected behavioral changes occurred during administration of ropivacaine. The
      patients became extremely agitated, anxious, and screamed, and they did not
      respond to verbal commands. CONCLUSION: This case report shows that ropivacaine
      may cause CNS toxicity that differs from classical signs of local anesthetic
      induced toxicity. This effect might be related to the unique structure of
      ropivacaine, which is formulated in an S-enantiomer preparation. It has been
      shown that S-enantiomers bind differently to receptors in both the CNS and
      cardiovascular systems. This property may account for the disinhibition of select
      neural pathways that are specifically involved in mediation of anxiety and
      aggression.

PMID- 10204907
TI  - Labor analgesia with paravertebral lumbar sympathetic block.
AB  - BACKGROUND AND OBJECTIVES: Provision of labor analgesia continues to be a
      challenge for parturients with spine pathology or history of back surgery.
      METHODS: We report on the use of paravertebral lumbar sympathetic block for first
      stage labor analgesia in two parturients with spine pathology.

PMID- 10204908
TI  - A new application for superior laryngeal nerve block: treatment or prevention of
      laryngospasm and stridor.

PMID- 10204909
TI  - Intrathecal drug spread and duration of block.

PMID- 10204910
TI  - Lower lip ulceration after neurolytic mandibular nerve block.

PMID- 10204911
TI  - Response to comments by Omoigui in: A safer technique utilizing an intravenous
      catheter introducer for epidural catheter lysis of adhesions.

PMID- 10204912
TI  - Unintentional unusual placement of a spinal catheter into the epidural space.

PMID- 10204913
TI  - Pectorialis major in interscalene brachial plexus blockade.

PMID- 10204914
TI  - Problems with combined spinal and epidural anesthesia.

PMID- 10204916
TI  - Localization of the axillary artery in brachial plexus block.

PMID- 10204915
TI  - Analgesia with continuous lateral posterior tibial nerve block.

PMID- 10204918
TI  - Genes and orthopaedics.

PMID- 10204917
TI  - Alkalinization of local anesthetics.

PMID- 10204919
TI  - Bracing (and screening)--yes or no?

PMID- 10204920
TI  - Patterns of weight distribution under the metatarsal heads.
AB  - The longitudinal arch between the heel and the forefoot and the transverse arch
      between the first and fifth metatarsal heads, absorb shock, energy and force. A
      device to measure plantar pressure was used in 66 normal healthy subjects and in
      294 patients with various types of foot disorder. Only 22 (3%) of a total of 720
      feet, had a dynamic metatarsal arch during the stance phase of walking, and all
      had known abnormality. Our findings show that there is no distal transverse
      metatarsal arch during the stance phase. This is important for the classification
      and description of disorders of the foot.

PMID- 10204921
TI  - Arthroscopy of the first metatarsophalangeal joint.
AB  - We carried out 12 arthroscopies of the first metatarsophalangeal (MTP) joint in
      11 patients over a five-year period. Their mean age was 30 years (15 to 58) and
      the mean duration of symptoms before surgery was eight months (1 to 24). Six
      patients had an injury to the joint; all had swelling and tenderness with a
      reduced range of movement. In six patients, radiographs revealed no abnormality.
      Under general anaesthesia with a tourniquet the hallux is suspended by a large
      Chinese finger trap to distract the joint. Using a 1.9 mm 30 degree oblique
      arthroscope the MTP joint is inspected through dorsomedial and dorsolateral
      portals with a medial portal if necessary. All patients were found to have intra
      articular pathology, which was treated using small instruments. The mean follow
      up was 19.3 months (6 to 62) and all patients had no or minimal pain, decreased
      swelling and an increased range of movement of the affected joint.

PMID- 10204922
TI  - Mechanical properties of heel pads reconstructed with flaps.
AB  - We compared the mechanical properties of normal and reconstructed heel pads in
      seven patients. Four had latissimus dorsi flaps and one each an anterior thigh
      flap, a local dorsalis pedis flap and a sural arterial flap. The thickness of the
      heel pad was measured under serial incremental loads of 0.5 kg to a maximum of 3
      kg and then relaxed sequentially. The load-displacement curve of the heel pad
      during a loading-unloading cycle was plotted and from this the unloaded heel-pad
      thickness (UHPT), compressibility index (CI), elastic modulus (Ep), and energy
      dissipation ratio (EDR) were calculated. The EDR was significantly increased in
      the reconstructed heels (53.7 +/- 18% v 23.4 +/- 6.5%, p = 0.003) indicating that
      in them more energy is dissipated as heat. Insufficient functional capacity in
      the reconstructed heel pad can lead to the development of shock-induced
      discomfort and ulceration.

PMID- 10204923
TI  - Isolated and combined lesions of the axillary nerve. A review of 146 cases.
AB  - We have assessed the final strength of the deltoid in 121 patients who had repair
      of isolated or combined lesions of the axillary (circumflex) nerve and were
      available for statistical analysis. Successful or useful results were achieved in
      85% after grafting of isolated lesions. The strength was statistically better
      when patients had grafting of the axillary nerve within 5.3 months from the time
      of injury. The dramatic decrease in the rate of success seen with longer delays
      suggests that surgery should be undertaken within three months of injury. A
      statistically significant downward trend of the rate of success was noted with
      increasing age. The force and level of injury to the shoulder play an important
      role in the type, combination and level of nerve damage and the incidence of
      associated rotator-cuff, vascular and other injuries to the upper limb.
      Management of isolated and combined lesions of the axillary nerve after injury to
      the shoulder needs to be thorough and systematic.

PMID- 10204924
TI  - The inferior capsular shift operation for instability of the shoulder. Long-term
      results in 34 shoulders.
AB  - We reviewed 26 patients with 34 shoulders treated by the inferior capsular shift
      operation for inferior and multidirectional instability. The mean follow-up was
      8.3 years. In total, 12 shoulders showed voluntary subluxation. Eight operations
      used an anterior and posterior approach, 11 were by the posterior route, and 15
      shoulders had an anterior approach. In 30 shoulders (85%) the outcome was
      satisfactory and 20 (59%) scored good or excellent results on the Rowe system.
      Instability had recurred in nine shoulders (26%) from three months to three years
      after the operation. Six of the 12 shoulders with voluntary subluxation (50%) had
      recurrence, as against three of the other 22 (14%), a statistically significant
      difference. The operation is therefore not indicated for voluntary subluxation.
      The 19 shoulders which had been assessed in 1987 at a mean of 3.5 years after
      surgery, were also reviewed in 1995 and found to have no significant changes in
      instability or Rowe score. This shows that the capsular shift appeared to have
      maintained its tension over an eight-year period. After the use of a posterior
      approach, 64% of the shoulders showed a posterolateral defect on radiographs of
      the humerus.

PMID- 10204925
TI  - Sensory pathways in the spinal accessory nerve.
AB  - We obtained samples of spinal accessory nerve from patients undergoing radical
      surgery for tumours or nerve grafting in the neck. These were analysed by light
      and electron microscopy for the type of fibre. All contained fibres consistent
      with non-proprioceptive sensory function including pain.

PMID- 10204926
TI  - Effectiveness of the A-V impulse hand pump.
AB  - Acute swelling of the hand is a common problem after trauma or surgery and is
      associated with both pain and loss of function. We describe a prospective study
      of 47 patients in which we assessed the effects of a pneumatic compression device
      (A-V impulse hand pump) on the swollen hand. The pump reduced swelling by
      increasing the velocity of venous return as demonstrated by Duplex scanning of
      the median cubital vein. Continuous use of the pump for 48 hours gave a reduction
      of 78.6% in swelling of the injured hand compared with the opposite, uninjured
      side. Even when used intermittently, with the pump on for 12 hours out of 24, a
      statistically significant effect was seen. There was a subjective reduction in
      pain and an objective improvement in function of the hand. Use of the pump
      resulted in a nearly normal hand by the time of discharge from hospital after, on
      average, 48 hours.

PMID- 10204927
TI  - The assessment of appropriate indications for laminectomy.
AB  - We have developed criteria to determine the appropriate indications for lumbar
      laminectomy, using the standard procedure developed at the RAND corporation and
      the University of California at Los Angeles (RAND-UCLA). A panel of five surgeons
      and four physicians individually assessed 1000 hypothetical cases of sciatica,
      back pain only, symptoms of spinal stenosis, spondylolisthesis, miscellaneous
      indications or the need for repeat laminectomy. For the first round each member
      of the panel used a scale ranging from 1 (extremely inappropriate) to 9
      (extremely appropriate). After discussion and condensation of the results into
      three categories laminectomy was considered appropriate in 11% of the 1000
      theoretical scenarios, equivocal in 26% and inappropriate in 63%. There was some
      variation between the six categories of malalignment, but full agreement in 64%
      of the hypothetical cases. We applied these criteria retrospectively to the
      records of 196 patients who had had surgical treatment for herniated discs in one
      Swiss University hospital. We found that 48% of the operations were for
      appropriate indications, 29% for equivocal reasons and that 23% were
      inappropriate. The RAND-UCLA method is a feasible, useful and coherent approach
      to the study of the indications for laminectomy and related procedures, providing
      a number of important insights. Our conclusions now require validation by
      carefully designed prospective clinical trials, such as those which are used for
      new medical techniques.

PMID- 10204928
TI  - Delayed vertebral slip and adjacent disc degeneration with an isthmic defect of
      the fifth lumbar vertebra.
AB  - We reviewed the radiographs of 325 unselected patients with defects in the pars
      interarticularis of L5 to study whether the incidence of vertebral slip in
      spondylolysis of L5 remained unchanged after the age of 20 years. MRI was also
      carried out on 111 of the patients to investigate the relationship between the
      shape of the transverse process of L5 and the degeneration of the discs adjacent
      to this level. The incidence of spondylolisthesis increased with age from 17% in
      the second decade to 51% in the sixth. The transverse process was significantly
      more slender in patients with less degeneration at L4/5 and advanced degeneration
      at L5/S1 than in patients with advanced degeneration at L4/5 and less
      degeneration at L5/S1. Vertebral slip secondary to an isthmic defect of L5 after
      the age of 20 years was confirmed and the adjacent disc degeneration was
      significantly related to the vertical thickness of the transverse process of L5.

PMID- 10204929
TI  - Congenital kyphosis in myelomeningocele. The effect of cordotomy on bladder
      function.
AB  - To determine the effect of cordotomy on the function of the bladder during
      surgical correction of congenital kyphosis in myelomeningocele, we reviewed 13
      patients who had this procedure between 1981 and 1996. The mean age of the
      patients at operation was 8.9 years (3.7 to 16) and the mean follow-up was 4.8
      years (1.3 to 10.8). Bladder function before and after operation was assessed
      clinically and quantitatively by urodynamics. The mean preoperative kyphosis was
      117 degrees (52 to 175) and decreased to 49 degrees (1 to 89) immediately after
      surgery. At the latest follow-up, a mean correction of 52% had been achieved.
      Only one patient showed deterioration in bladder function after operation. Eight
      out of the nine patients who had urodynamic assessment had improvement in bladder
      capacity and compliance, and five showed an increase in urethral pressure. One
      patient developed a spastic bladder and required subsequent surgical
      intervention. Cordotomy, at or below the level of the kyphosis, allows excellent
      correction of the structural deformity.

PMID- 10204930
TI  - Congenital convex pes valgus.
AB  - Congenital convex pes valgus (congenital vertical talus) is a rare condition. We
      reviewed ten feet in seven patients who had had surgical correction. All had been
      operated on by the senior author (JF) and the same surgical technique was used
      throughout, incorporating transfer of the tibialis anterior to the neck of the
      talus. The mean age at surgery was 31 months and the mean follow-up was nine
      years (6 to 14). All patients completed a questionnaire and had clinical,
      radiological and photographic evaluation performed by an independent examiner.
      None had required further surgery. All but one were satisfied with the result,
      and had no functional limitations. They all wore normal shoes. The mean ankle
      dorsiflexion was 17 degrees and plantar flexion 21 degrees. The mean arc of
      subtalar motion was 27 degrees. All radiological parameters measured were within
      the normal range, although irregularity of the talonavicular joint was common. No
      avascular necrosis of the body of the talus was seen. We conclude that the medium
      term results of this procedure are very satisfactory.

PMID- 10204931
TI  - Ultrasound screening for hips at risk in developmental dysplasia. Is it worth it?
AB  - Between May 1992 and April 1997, there were 20,452 births in the Blackburn
      District. In the same period 1107 infants with hip 'at-risk' factors were
      screened prospectively by ultrasound. We recorded the presence of dislocation and
      dysplasia detected under the age of six months using Graf's alpha angle. Early
      dislocation was present in 36 hips (34 dislocatable and 2 irreducible). Of the 36
      unstable hips, 30 (83%) were referred as being Ortolani-positive or unstable; 25
      (69%) of these had at least one of the risk factors. Only 11 (31%) were
      identified from the 'at-risk' screening programme alone (0.54 per 1000 live
      births). Eight cases of 'late' dislocation presented after the age of six months
      (0.39 per 1000 live births). The overall rate of dislocation was 2.2 per 1000
      live births. Only 31% of the dislocated hips belonged to a major 'at-risk' group.
      Statistical analysis confirmed that the risk factors had a relatively poor
      predictive value if used as a screening test for dislocation. In infants referred
      for doubtful clinical instability, one dislocation was detected for every 11
      infants screened (95% confidence interval (CI) 8 to 17) whereas in infants
      referred because of the presence of any of the major 'at-risk' factors the rate
      was one in 75 (95% CI 42 to 149). Routine ultrasound screening of the 'at-risk'
      groups on their own is of little value in significantly reducing the rate of
      'late' dislocation in DDH, but screening clinically unstable hips alone or
      associated with 'at-risk' factors has a high rate of detection.

PMID- 10204932
TI  - The influence of weight-bearing on the measurement of polyethylene wear in THA.
AB  - We have studied the influence of weight-bearing on the measurement of wear of the
      polyethylene acetabular component in total hip arthroplasty using two techniques.
      The measured vertical wear was significantly greater when radiographs were taken
      weight-bearing rather than with the patient supine (p = 0.001, method 1; p =
      0.007, method 2). Calculations of rates of linear wear of the acetabular
      component were significantly underestimated (p < 0.05) when radiographs were
      taken supine. There are two reasons for this. First, a change in pelvic
      orientation when bearing weight ensures that the thinnest polyethylene is brought
      into relief, and secondly, the head of the femoral component assumes the position
      of maximal displacement along its wear path. Interpretation of previous studies
      on both linear and volumetric polyethylene wear in total hip arthroplasty should
      be reassessed in the light of these findings.

PMID- 10204933
TI  - Accuracy of EBRA-FCA in the measurement of migration of femoral components of
      total hip replacement. Einzel-Bild-Rontgen-Analyse-femoral component analysis.
AB  - Several methods of measuring the migration of the femoral component after total
      hip replacement have been described, but they use different reference lines, and
      have differing accuracies, some unproven. Statistical comparison of different
      studies is rarely possible. We report a study of the EBRA-FCA method (femoral
      component analysis using Einzel-Bild-Rontgen-Analyse) to determine its accuracy
      using three independent assessments, including a direct comparison with the
      results of roentgen stereophotogrammetric analysis (RSA). The accuracy of EBRA
      FCA was better than +/- 1.5 mm (95% percentile) with a Cronbach's coefficient
      alpha for interobserver reliability of 0.84; a very good result. The method had a
      specificity of 100% and a sensitivity of 78% compared with RSA for the detection
      of migration of over 1 mm. This is accurate enough to assess the stability of a
      prosthesis within a relatively limited period. The best reference line for
      downward migration is between the greater trochanter and the shoulder of the
      stem, as confirmed by two experimental analyses and a computer-assisted design.

PMID- 10204934
TI  - The prediction of failure of the stem in THR by measurement of early migration
      using EBRA-FCA. Einzel-Bild-Roentgen-Analyse-femoral component analysis.
AB  - We report the ten-year results for three designs of stem in 240 total hip
      replacements, for which subsidence had been measured on plain radiographs at
      regular intervals. Accurate migration patterns could be determined by the method
      of Einzel-Bild-Roentgen-Analyse-femoral component analysis (EBRA-FCA) for 158
      hips (66%). Of these, 108 stems (68%) remained stable throughout, and five (3%)
      started to migrate after a median of 54 months. Initial migration of at least 1
      mm was seen in 45 stems (29%) during the first two years, but these then became
      stable. We revised 17 stems for aseptic loosening, and 12 for other reasons.
      Revision for aseptic loosening could be predicted by EBRA-FCA with a sensitivity
      of 69%, a specificity of 80%, and an accuracy of 79% by the use of a threshold of
      subsidence of 1.5 mm during the first two years. Similar observations over a five
      year period allowed the long-term outcome to be predicted with an accuracy of
      91%. We discuss the importance of four different patterns of subsidence and
      confirm that the early measurement of migration by a reasonably accurate method
      can help to predict long-term outcome. Such methods should be used to evaluate
      new and modified designs of prosthesis.

PMID- 10204935
TI  - Retroversion of the acetabulum. A cause of hip pain.
AB  - We describe a little-known variety of hip dysplasia, termed 'acetabular
      retroversion', in which the alignment of the mouth of the acetabulum does not
      face the normal anterolateral direction, but inclines more posterolaterally. The
      condition may be part of a complex dysplasia or a single entity. Other than its
      retroversion, the acetabulum is sited normally on the side wall of the pelvis,
      and its articular surface is of normal extent and configuration. The retroverted
      orientation may give rise to problems of impingement between the femoral neck and
      anterior acetabular edge. We define the clinical and radiological parameters and
      discuss pathological changes which may occur in the untreated condition. A
      technique of management is proposed.

PMID- 10204936
TI  - Improving the detection of acetabular osteolysis using oblique radiographs.
AB  - Visualisation of periacetabular osteolysis by standard anteroposterior (AP)
      radiographs underestimates the extent of bone loss around a metal-backed
      acetabular component. We have assessed the effectiveness of standard radiological
      views in depicting periacetabular osteolysis, and recommend additional
      projections which make these lesions more visible. This was accomplished using a
      computerised simulation of radiological views and a radiological analysis of
      simulated defects placed at regular intervals around the perimeter of a cadaver
      acetabulum. The AP view alone showed only 38% of the defects over all of the
      surface of the cup and failed to depict a 3 mm lesion over 83% of the cup. When
      combined with the AP view, additional 45 degree obturator-oblique and iliac
      oblique projections increased the depiction, showing 81% of the defects. The
      addition of the 60 degree obturator-oblique view further improved the
      visualisation of posterior defects, increasing the rate of detection to 94%.
      Based on this analysis, we recommend using at least three radiographic views when
      assessing the presence and extent of acetabular osteolysis.

PMID- 10204937
TI  - Total knee arthroplasty in bony ankylosis in gross flexion.
AB  - Between June 1993 and December 1994, we performed total knee arthroplasty (TKA)
      on 27 knees in 24 patients with spontaneous bony ankylosis in severe flexion. The
      mean age at operation was 43.5 years (30 to 60). No patient had preoperative
      pain. Three were unable to walk and 21 could manage less than five blocks. The
      mean duration of the ankylosis was 18.7 years (13 to 25) and its mean position
      was 105 degree flexion (75 to 135). The preoperative Hospital for Special Surgery
      Knee Score of 60 points was improved to 87 at the final follow-up three to five
      years later. All knees were free from pain. The mean range of active flexion in
      24 knees was 97 degrees (78 to 115) and the mean arc of movement 91 degrees (78
      to 98). The mean fixed flexion deformity was 6 degrees (0 to 25) and the
      extension lag 8 degrees (0 to 25). Angular deformity was corrected to between 0
      degrees and 10 degrees of valgus. Four patients were able to walk one block and
      20 five to seven blocks. Thirteen knees (48%) showed some necrosis at the skin
      edge; one knee required arthrodesis and another resection arthroplasty. One had a
      recurrence of tuberculous infection requiring arthrodesis. One patient had a
      rupture of the quadriceps tendon. To date no prosthesis has required revision for
      loosening. Radiolucency of 1 mm or less about the tibial prosthesis was observed
      at follow-up in four of the 24 knees. Our results have shown that one-stage TKA
      and skeletal traction after operation can achieve correction of severe flexion
      deformity of the knee with marked improvement in the function and quality of
      life.

PMID- 10204938
TI  - Intra-articular morphine and/or bupivacaine after total knee replacement.
AB  - The postoperative analgesic effects of intra-articular injections of bupivacaine
      and/or morphine were examined prospectively in 437 patients who had total knee
      replacement for osteoarthritis. They were divided randomly into four groups.
      Group I received 10 mg of morphine (1 ml) and 9 ml of saline, group II received
      10 ml of bupivacaine (2.5 mg/ml), group III received 10 ml of saline, and group
      IV received 10 mg of morphine (1 ml) and 9 ml of bupivacaine (2.5 mg/ml). All
      analgesics administered in the first 24 hours after operation were recorded. The
      patients rated their pain on the McGill-Melzack scale at 1, 6, 12 and 24 hours.
      No significant differences were found between any of the groups in the use of
      Demoral and/or Toradol in 24 hours, the length of stay in hospital or the pain
      rating at 1, 6, 12 or 24 hours. Patients in groups I and IV, whose injections
      included morphine, used significantly more morphine in the first 24 postoperative
      hours than did groups II or III.

PMID- 10204939
TI  - Mucoid cystic degeneration of the cruciate ligament.
AB  - A 35-year-old man was seen with pain in the back of the knee. MRI showed a mass
      in the anterior cruciate ligament. Biopsy indicated mucoid degeneration.
      Arthroscopic resection of the ligament was carried out, with relief of symptoms.

PMID- 10204940
TI  - Salvage of the head of the radius after fracture-dislocation of the elbow. A case
      report.
AB  - We describe a patient with a Mason type-III fracture of the head of the radius
      associated with traumatic dislocation of the elbow. The radial head was intact
      throughout its circumference despite being completely detached from the shaft and
      devoid of any soft-tissue attachments. Severe comminution of the radial neck
      prevented reconstruction by internal fixation and precluded prosthetic
      replacement of the head. The head was fixed to the shaft with a tricortical iliac
      crest bone graft which replaced the neck. Two years later, the patient had a
      stable elbow with flexion from 10 degrees to 130 degrees. Radiologically, the
      head of the radius appeared to be viable and the bone graft had incorporated.

PMID- 10204941
TI  - 'Floating pelvis'. A combination of bilateral hip dislocation with a lumbar
      ligamentous disruption.
AB  - A patient is described with a ligamentous disruption at the L4/L5 level in
      association with bilateral, traumatic dislocations of the hip. The diagnostic
      evaluation, acute intervention, and definitive stabilisation are reported. The
      unstable spine posed a problem in treatment with regard to the timing and
      technique of the reduction of the hips.

PMID- 10204942
TI  - Malunion in the lower limb. A nomogram to predict the effects of osteotomy.
AB  - Nomograms derived from mathematical analysis indicate that the level of malunion
      is the most important determinant of changes in the moment arm of the knee, the
      plane of the ankle and alterations in limb length. Testing in five patients
      undergoing reconstruction showed a mean error of postoperative limb length of 2.2
      mm (SD 0.8 mm), knee moment arm of 4.7 mm (SD 3.3 mm) and ankle angle of 2.6
      degrees (SD 2.3 degrees). These nomograms provide the information required when
      assessing whether a particular degree of angulation may be accepted.

PMID- 10204943
TI  - Tumour volume as a predictor of necrosis after chemotherapy in Ewing's sarcoma.
AB  - We studied the CT and MR scans, and the histology of 50 patients with primary
      Ewing's sarcoma of bone to determine the association between the change in tumour
      volume and necrosis after chemotherapy, and to ascertain their influence on
      prognosis. The mean age of the patients was 17 years. The limbs were involved in
      40 and the axial bones in ten. The volume of the tumour at diagnosis varied from
      31 to 1790 ml. There was a significant relationship between necrosis and the
      measured change in volume of the tumour after chemotherapy. Progression of the
      tumour despite chemotherapy was seen only in patients with necrosis of grades 4
      to 6. Necrosis significantly influenced survival (p < 0.05), but the effect of
      change in volume was less significant. Change in volume of the tumour is a good
      predictor of necrosis induced by chemotherapy. Necrosis is a strong prognostic
      factor in Ewing's sarcoma.

PMID- 10204944
TI  - Clinical and radiological aspects of idiopathic diabetic muscle infarction.
      Rational approach to diagnosis and treatment.
AB  - The systemic effects of diabetes mellitus are well recognised. The heart, kidney,
      central and peripheral nervous systems, and the distal parts of the limbs are
      often the site of end-organ damage resulting from ischaemia. Infarction of large
      muscle groups in the limb, not associated with gangrene, is uncommon. There have
      been few reported cases other than radiological descriptions of diabetic muscle
      infarcts. While previous reports have illustrated some of the clinical and
      radiological characteristics of this condition, the paucity of published cases
      makes it difficult to determine the most appropriate methods of diagnosis and
      treatment. During a five-year period we treated 14 patients with diabetes
      mellitus, aged from 32 to 59 years, who were referred to a musculoskeletal
      oncology service for suspected soft-tissue sarcoma, but were subsequently found
      to have a diabetic muscle infarct. Closed needle biopsy was performed in 13
      without complications. In 12 patients, the symptoms resolved without surgical
      treatment.

PMID- 10204945
TI  - The prevalence and clinicopathological appearance of extension of osteonecrosis
      in the femoral head.
AB  - In about 50% of cases, osteonecrosis of the femoral head is known to occupy more
      than one site. There is controversy as to whether a single focus may increase in
      size. We have reviewed 606 consecutive femoral heads which had been surgically
      removed for osteonecrosis. Extension of osteonecrosis was observed in only two
      (0.3%) and was confirmed histopathologically by the enlargement of the necrotic
      segment beyond the repair zone formed for the primary necrosis into the adjacent,
      previously uninvolved bone. In both cases, the necrotic regions were wedge-shaped
      and occupied over 80% of the femoral head. It appears that an increase in size is
      extremely rare and that osteonecrosis is due to a single event. Our findings may
      be of value in assessing the use of joint-salvage procedures for osteonecrosis of
      the femoral head.

PMID- 10204946
TI  - The pathology of bone allograft.
AB  - We analysed the histological findings in 1146 osteoarthritic femoral heads which
      would have been considered suitable for bone-bank donation to determine whether
      pathological lesions, other than osteoarthritis, were present. We found that 91
      femoral heads (8%) showed evidence of disease. The most common conditions noted
      were chondrocalcinosis (63 cases), avascular necrosis (13), osteomas (6) and
      malignant tumours (one case of low-grade chondrosarcoma and two of well
      differentiated lymphocytic lymphoma). There were two with metabolic bone disease
      (Paget's disease and hyperparathyroid bone disease) and four with inflammatory
      (rheumatoid-like) arthritis. Our findings indicate that occult pathological
      conditions are common and it is recommended that histological examination of this
      regularly used source of bone allograft should be included as part of the
      screening protocol for bone-bank collection.

PMID- 10204947
TI  - Histopathology of retrieved allografts of the femoral head.
AB  - From November 1994 to March 1997, we harvested 137 grafts of the femoral head
      from 125 patients for donation during total hip arthroplasty according to the
      guidelines of the American Associations of Tissue Banks (AATB) and the European
      Association of Musculo-Skeletal transplantation (EAMST). In addition to the
      standards recommended by these authorities, we performed histopathological
      examination of a core biopsy of the retrieved bone allograft and of the synovium.
      Of the 137 allografts, 48 (35.0%) fulfilled all criteria and were free for
      donation; 31 (22.6%) were not regarded as suitable for transplantation because
      the serological retests at six months were not yet complete and 58 (42.3%) were
      discarded because of incomplete data. Of those discarded, five showed abnormal
      histopathological findings; three were highly suspicious of low-grade B-cell
      lymphoma, one of monoclonal plasmacytosis and the other of non-specific
      inflammation of bone marrow. However, according to the standards of the AATB or
      EAMST they all met the criteria and were eligible for transplantation. Our
      findings indicate that the incidence of abnormal histopathology in these
      retrieved allografts was 3.6%. Since it is essential to confirm the quality of
      donor bones in bone banking, we advise that histopathological screening of donor
      bone should be performed to exclude abnormal allografts.

PMID- 10204948
TI  - Changes in allograft bone irradiated at different temperatures.
AB  - Secondary sterilisation of allograft bone by gamma irradiation is common, but the
      conditions under which it is performed vary between tissue banks. Some do so at
      room temperature, others while the bone is frozen. Bone is made brittle by
      irradiation because of the destruction of collagen alpha chains, probably
      mediated by free radicals generated from water molecules. Freezing reduces the
      mobility of water molecules and may therefore decrease the production of free
      radicals. We found that bone irradiated at -78 degrees C was less brittle and had
      less collagen damage than when irradiated at room temperature. These findings may
      have implications for bone-banking.

PMID- 10204949
TI  - Intracapsular components do not change hip proprioception.
AB  - We compared joint proprioception in 12 hips in 12 patients with hemiarthroplasty
      after fracture of the hip, in 12 hips in 11 patients with total hip arthroplasty
      because of osteoarthritis and in a control group of 12 age-matched patients with
      no clinical complaints. There was no significant difference (p = 0.05) in joint
      proprioception in any of the groups. There was no decrease in joint
      proprioception in the group with total hip arthroplasty compared with the
      hemiarthroplasty group or with the control group. Other factors such as stretch
      receptors in the adjacent tendons and muscles may have a greater influence on
      proprioception in the hip than the intracapsular components.

PMID- 10204950
TI  - Decrease in the mesenchymal stem-cell pool in the proximal femur in
      corticosteroid-induced osteonecrosis.
AB  - We have evaluated bone-marrow activity in the proximal femur of patients with
      corticosteroid-induced osteonecrosis and compared it with that of patients with
      osteonecrosis related to sickle-cell disease and with a control group without
      osteonecrosis. Bone marrow was obtained by puncture of the femoral head outside
      the area of necrosis and in the intertrochanteric region. The activity of stromal
      cells was assessed by culturing fibroblast colony-forming units (FCFUs). We found
      a decrease in the number of FCFUs outside the area of osteonecrosis in the upper
      end of the femur of patients with corticosteroid-induced osteonecrosis compared
      with the other groups. We suggest that glucocorticosteroids may also have an
      adverse effect on bone by decreasing the number of progenitors. The possible
      relevance of this finding to osteonecrosis is discussed.

PMID- 10204951
TI  - Stimulation of the inflammatory system by reamed and unreamed nailing of femoral
      fractures. An analysis of the second hit.
AB  - It has been suggested that reamed intramedullary nailing of the femur should be
      avoided in some patients with multiple injuries. We have studied prospectively
      the effect of femoral reaming on the inflammatory process as implicated in the
      pathogenesis of acute respiratory distress syndrome (ARDS) and multiple-organ
      failure (MOF). We studied changes in the levels of serum interleukin-6 (IL-6)
      (proinflammatory cytokine), neutrophil CD11b (C3) receptor expression (activated
      neutrophil adhesion molecule), serum soluble intracellular adhesion molecule (s
      ICAM-1), serum soluble E-selectin (the soluble products of endothelial adhesion
      molecules) and plasma elastase (neutrophil protease) in a series of patients with
      femoral fractures treated by nailing. We have also compared reamed nailing with
      unreamed nailing. We found that the levels of serum IL-6 and elastase rose
      significantly during the nailing procedure indicating a measurable 'second hit'.
      There was no clear response in leukocyte activation and no difference in the
      release of endothelial adhesion molecule markers. There was no significant
      difference between groups treated by reamed and unreamed nailing. Although
      clinically unremarkable, the one patient who died from ARDS was shown to be
      hyperstimulated after injury and again after nailing, suggesting the importance
      of an excessive inflammatory reaction in the pathogenesis of these serious
      problems. Our findings have shown that there is a second hit associated with
      femoral nailing and suggest that the degree of the inflammatory reaction may be
      important in the pathogenesis of ARDS and MOF.

PMID- 10204952
TI  - Ipsilateral recurrent lumbar disc herniation.

PMID- 10204953
TI  - Redisplaced unstable fractures of the distal radius.

PMID- 10204954
TI  - Hydroxyapatite augmentation of the porous coating improves fixation of tibial
      components.

PMID- 10204955
TI  - The role of methylmethacrylate monomer in the formation and haemodynamic outcome
      of pulmonary fat emboli.

PMID- 10204956
TI  - Ankle fractures in diabetics.

PMID- 10204957
TI  - A new test for estimating iliotibial band contracture.

PMID- 10204958
TI  - The treatment of subluxation of the hip in children over the age of four years.

PMID- 10204959
TI  - Incisional cellulitis after total hip replacement.

PMID- 10204960
TI  - Acute compartment syndrome of the thigh after joint replacement with
      anticoagulation.

PMID- 10204961
TI  - Femoral stem fixation.

PMID- 10204963
TI  - Thyroid axis sustaining hypothesis of posttraumatic stress disorder.

PMID- 10204964
TI  - Social environment and longevity in schizophrenia.
AB  - OBJECTIVE: The role of social support as a predictor of long-term survival among
      patients with schizophrenia was examined. METHODS: Social histories were
      abstracted from the medical records of a cohort of 133 deceased schizophrenic
      patients admitted for inpatient treatment between 1934 and 1944. Two independent
      raters assessed the quantity and quality of support available in each patient's
      social environment. RESULTS: Cox regression analysis revealed that higher
      quantity of social support was significantly related to survival time (p<.05)
      after controlling for marital status and quality of support. The Cox model
      indicated that a 1-point increase in the support quantity rating was associated
      with a proportional 25% decrease in the hazard rate. CONCLUSIONS: The present
      findings suggest that social environment, specifically the quantity of social
      support available to the patient, may impact longevity in psychiatric
      populations.

PMID- 10204962
TI  - Elevations of serum T3 levels and their association with symptoms in World War II
      veterans with combat-related posttraumatic stress disorder: replication of
      findings in Vietnam combat veterans.
AB  - OBJECTIVE: In previous serum thyroid studies, we reported an unusual thyroid
      profile, including elevated levels of total and free triiodothyronine (T3), total
      thyroxine (T4), and thyroxine-binding globulin (TBG) with no elevations in free
      T4 and thyrotropin (TSH) in Vietnam veterans with combat-related posttraumatic
      stress disorder (PTSD) compared to control subjects. In a subsample of Vietnam
      veterans, we found a significant positive correlation between total T3, free T3,
      and PTSD symptoms, specifically hyperarousal symptoms. In the present study, we
      explored the generalizability of our findings to World War II (WWII) veterans
      with PTSD. METHOD: Clinical symptoms were assessed in and serum thyroid measures
      were obtained from 12 WWII veterans with PTSD and 18 WWII veterans without PTSD.
      RESULTS: WWII veterans with combat-related PTSD showed elevations of serum total
      and free T3 with no elevations of free T4 and TSH compared to control subjects,
      replicating the results of our previous studies. A significant positive
      relationship between total and free T3 and PTSD symptoms, specifically
      hyperarousal symptoms, was also replicated in the total WWII group. Elevations of
      total T4 and TBG were not replicated in the WWII group with PTSD, which may
      indicate a shift with age in the free/bound dynamics of the thyroid alterations
      observed. CONCLUSIONS: This study supports the observation that the thyroid
      system is altered in chronic combat-related PTSD. The observed alterations of
      thyroid function along with PTSD symptoms appear to be chronic, detectable 50
      years after the war.

PMID- 10204965
TI  - Observational versus experimental studies: would the results be similar?

PMID- 10204966
TI  - Psychological factors in functional gastrointestinal disorders: characteristics
      of the disorder or of the illness behavior?
AB  - OBJECTIVE: This study examines factors affecting the frequency of physician
      consultations by individuals with functional gastrointestinal disorders (FGD) in
      a group of subjects with functional dyspepsia or irritable bowel syndrome.
      Systematic selection of persons who were already seeing a physician for one of
      these problems was avoided by conducting an epidemiological field study rather
      than a clinical study. METHODS: A representative sample of the German population
      (N=2201) completed a questionnaire that included, in addition to the criterion
      (number of physician visits in the past 12 months), items aimed at identifying
      the target group and questions about physical symptoms, illness behavior, living
      situation, personality features, and sociodemographic status (a total of 31
      predictors). RESULTS: Individuals with functional gastrointestinal disorders who
      consulted a physician for their gastrointestinal disorders and those who did not
      differed significantly, especially on psychological measures. The differences
      between these individuals and the general population were greater for the
      consulters than for the nonconsulters. Multiple regression analyses yielded nine
      predictors that explained 40.2% of the variance of the criterion. The best
      predictors of frequency of physician consultations were the duration of periods
      with symptoms and psychological factors, such as the severity of depression and
      the patients' views on the cause of their illness. CONCLUSIONS: The
      psychopathology seen in people with functional gastrointestinal disorders is of
      two types: one is a characteristic of the illness itself and the other leads the
      individual to consult a physician. When gastroenterologists see patients with
      such disorders, they can assume that they may be dealing with a self-selected
      group of individuals with psychological stress. Psychological assessment would,
      therefore, be useful to determine whether a given individual with FGD might
      benefit from psychotherapy.

PMID- 10204967
TI  - Impact of gender, menstrual cycle phase, and oral contraceptives on the activity
      of the hypothalamus-pituitary-adrenal axis.
AB  - OBJECTIVE: Results from animal and human studies suggest that disregulations of
      the hypothalamus-pituitary-adrenal (HPA) axis are involved in several behavioral,
      circulatory, endocrine, and immune disorders with clear-cut gender differences in
      disease prevalence. The aim of the present study was to investigate sex-specific
      HPA response patterns with a focus on the contribution of gonadal steroids as
      possible mediators. METHODS: A total of 81 healthy adults were investigated in
      the present study. Twenty men, 19 women in the follicular phase of the menstrual
      cycle, 21 women in the luteal phase, and 21 women using oral contraceptives (OC)
      were exposed to a brief psychosocial stress test (Trier Social Stress Test; TSST)
      and injected with 0.25 mg ACTH1-24 on consecutive days. Basal HPA activity was
      investigated by repeatedly measuring cortisol levels immediately after awakening,
      as well as in 30-minute intervals from 9:00 AM to 9:00 PM. Additionally,
      questionnaires were used to assess psychological state and trait parameters.
      RESULTS: Results show that the TSST induced significant increases in ACTH,
      salivary-free cortisol, total plasma cortisol, and heart rates, as well as
      increased wakefulness and reduced calmness in the total group. Significant group
      differences emerged for ACTH and salivary-free cortisol stress responses:
      Although men showed higher ACTH responses to the TSST compared with each of the
      three groups of women, salivary cortisol responses showed the following response
      pattern: Luteal = Men > Follicular = OC. The salivary cortisol responses to ACTH1
      24 showed a similar response pattern: Luteal > Men > Follicular > OC. In
      contrast, total blood cortisol levels did not reveal any group difference between
      sexes or follicular versus luteal phase in either test. Although a similar
      salivary-free cortisol increase after awakening was found in the four groups, the
      circadian cortisol profile was significantly different throughout the first 4
      hours of sampling. Questionnaire-derived psychological variables, as measured in
      the present study, could not explain the observed results. CONCLUSIONS: We
      conclude that gender, menstrual cycle phase, and OC use exert important effects
      on HPA responsiveness to psychosocial stress in healthy subjects. Although men
      seem to have a stronger hypothalamic drive in response to stressful stimulation
      than women, differences in salivary-free cortisol levels, at least in part, may
      be explained by estradiol-induced changes in corticosteroid-binding protein
      levels. ACTH and cortisol secretion is not affected by OC use per se but the
      amount of bioavailable unbound cortisol ("free") is greatly reduced in this group
      of women after stimulation. Inasmuch as none of these differences between the
      study groups emerged in total blood cortisol levels, we strongly advocate for the
      simultaneous measurement of free and total cortisol levels in future studies on
      HPA functioning.

PMID- 10204968
TI  - Premenstrual symptomatology: role of prior knowledge about premenstrual syndrome.
AB  - OBJECTIVE: Most women have some premenstrual symptoms that may be influenced by
      diverse environmental factors. The aim of this study was to determine the
      influence of knowledge about premenstrual syndrome (PMS) in the reports of women
      and their symptoms. METHOD: We studied 86 healthy Mexican women whose highest
      level of education was sixth grade. Participants were assigned to one of two
      groups. The experimental group watched a videotape describing PMS and its
      negative consequences in daily life. The control group watched a videotape
      describing the menstrual cycle. The Menstrual Distress Questionnaire was
      administered to all women during the first week after menstruation, after which
      they were shown their designated videotape, and the questionnaire was
      administered again after the next menstruation. RESULTS: In the control group,
      there were no significant differences in premenstrual symptoms reported both
      before and after the women watched the videotape. However, women in the
      experimental group reported more severe premenstrual symptoms after watching the
      videotape. CONCLUSIONS: These results suggest that after observing the videotape,
      women's expectancies of negative symptoms in the premenstrual phase increased.
      Thus, the symptoms reported by these women were enhanced.

PMID- 10204970
TI  - Psychological stress, cytokine production, and severity of upper respiratory
      illness.
AB  - OBJECTIVE: The purpose of this study is to assess the role of psychological
      stress in the expression of illness among infected subjects and to test the
      plausibility of local proinflammatory cytokine production as a pathway linking
      stress to illness. METHODS: After completing a measure of psychological stress,
      55 subjects were experimentally infected with an influenza A virus. Subjects were
      monitored in quarantine daily for upper respiratory symptoms, mucus production,
      and nasal lavage levels of interleukin (IL)-6. RESULTS: Higher psychological
      stress assessed before the viral challenge was associated with greater symptom
      scores, greater mucus weights, and higher IL-6 lavage concentrations in response
      to infection. The IL-6 response was temporally related to the two markers of
      illness severity, and mediation analyses indicated that these data were
      consistent with IL-6 acting as a major pathway through which stress was
      associated with increased symptoms of illness. However, this pattern of data is
      also consistent with increases in IL-6 occurring in response to tissue damage
      associated with illness symptoms. CONCLUSIONS: Psychological stress predicts a
      greater expression of illness and an increased production of IL-6 in response to
      an upper respiratory infection.

PMID- 10204969
TI  - Vulnerable caregivers of patients with Alzheimer's disease have a deficit in
      circulating CD62L- T lymphocytes.
AB  - OBJECTIVE: The cell adhesion molecule, L-selectin (CD62L), serves a crucial role
      in the migration of naive T lymphocytes and is typically shed on cell activation.
      The objective of this study was to determine the effects of chronic stress on L
      selectin expression on peripheral lymphocytes in elderly spousal caregivers of
      patients with Alzheimer's disease. METHODS: Twenty caregivers (mean age, 73.5
      years) had their lymphocytes and catecholamine levels sampled at rest and in
      response to an acute psychological stressor. Ten of the caregivers were
      classified as susceptible or "vulnerable" based on the large amount of care
      required by the patient relative to the amount of respite the caregiver received
      during the previous 6 months. RESULTS: At rest, vulnerable caregivers had 60%
      fewer L-selectin negative CD8+ T cells (CD8+CD62L-) (p=.01) but no difference in
      CD8+CD62L+ cells. Vulnerable caregivers also showed significantly fewer CD4+CD62L
      T lymphocytes (p=.04) but no difference in CD4+CD62L+ lymphocytes. Resting
      plasma epinephrine levels were 44% higher in vulnerable caregivers as compared
      with nonvulnerable caregivers (p=.01). The acute stressor increased circulating
      levels of CD8+CD62L- and CD8+CD62L+ lymphocytes and catecholamines similarly in
      both groups. CONCLUSIONS: The findings suggest that caregivers who are more
      vulnerable to the chronic stress of caregiving show a decrement in circulating
      CD62L- T lymphocytes, possibly by adrenomedullary activation. The data also
      suggest the identity of lymphocyte subsets that may underlie prior observations
      of immunologic decrements associated with the chronic stress of caregiving.

PMID- 10204971
TI  - Anxiety and adherence to breast self-examination in women with a family history
      of breast cancer.
AB  - OBJECTIVE: Previous research has indicated low rates of adherence to monthly
      breast self-examination (BSE) in women with a family history of breast cancer,
      and anxiety has been identified as a major factor that may interfere with regular
      self-examination. However, the direction of the relationship between anxiety and
      BSE frequency remains unclear, with some studies indicating that high anxiety
      promotes adherence and others indicating that it leads to avoidance. The aim of
      the present study was to clarify the relationship between anxiety and adherence
      to breast self-examination by comparing the impact of general anxiety with that
      of cancer-specific anxiety on BSE frequency. METHODS: A sample of at-risk women
      (N=833) completed a questionnaire regarding BSE frequency, general anxiety,
      breast cancer worries, perceived risk of breast cancer, and family history of
      breast cancer. Women who self-examined infrequently (N=211), appropriately
      (N=462), or excessively (N=156) were compared on these variables. RESULTS:
      Statistical analyses indicated that general anxiety differentiated only between
      excessive self-examiners and less frequent self-examiners, with excessive self
      examiners reporting significantly higher general anxiety. Breast cancer worries
      differentiated between all three groups in a linear fashion, with increasing
      cancer worries associated with higher levels of BSE. CONCLUSIONS: In some at-risk
      women, high cancer anxiety may lead to high general anxiety and precipitate
      hypervigilant breast self-examination rather than avoidance. These findings are
      discussed in relation to psychoeducational interventions and genetic counseling
      services for women with a family history of breast cancer.

PMID- 10204972
TI  - Prospective data on sleep complaints and associated risk factors in an older
      cohort.
AB  - OBJECTIVE: The purpose of this study is to provide data on the prevalence of
      insomnia and hypersomnia among older persons, the stability of these sleep
      complaints over time, and factors associated with disturbed sleep, in particular
      age. METHOD: Data on symptoms of insomnia and hypersomnia were examined for the
      1994 to 1995 cohort of the Alameda County Study. In addition to age, the effects
      of gender, education, marital status, chronic medical conditions, functional
      impairment, life events, financial strain, and mood disturbance were examined
      using multiple logistic analyses. RESULTS: Prevalence in 1994 was 23.4% for
      insomnia and 6.8% for hypersomnia. There was moderate concordance between sleep
      complaints in 1994 and 1995 (kappa=.43). There was a tendency for insomnia and
      hypersomnia to increase with age in 1995, but not in 1994. Only gender, mood
      disturbance, and chronic health problems predicted insomnia. Life events, mood
      disturbance, and chronic conditions predicted hypersomnia. Age, net of the
      effects of other factors, was not associated with risk of either insomnia or
      hypersomnia. CONCLUSIONS: The results contribute to the expanding body of
      evidence concerning the important roles of psychological and somatic dysfunction
      in sleep disturbance. Age in and of itself is not a risk factor for insomnia or
      hypersomnia. That is, after adjustment for an array of putative risk factors for
      sleep problems, it seems the association between sleep difficulties and age is
      primarily due to depressed mood and physical health problems.

PMID- 10204973
TI  - Burnout, perceived stress, and cortisol responses to awakening.
AB  - OBJECTIVE: The effects of burnout and perceived stress on early morning free
      cortisol levels after awakening were investigated in a group of teachers.
      Previous studies revealed that cortisol levels show a significant increase after
      awakening, with high intraindividual stability. METHODS: Sixty-six teachers from
      local public schools (42 women and 24 men, mean age 42+/-5 years) were asked to
      sample saliva for cortisol analysis on 3 consecutive days. On each day, cortisol
      levels were measured at the time of awakening and 15, 30, and 60 minutes
      thereafter. On the night before the third day, subjects took 0.5 mg dexamethasone
      orally for testing glucocorticoid feedback inhibition. Burnout and perceived
      stress were measured by three different questionnaires. RESULTS: Perceived stress
      correlated with increases of cortisol levels during the first hour after
      awakening after dexamethasone pretreatment. In addition, teachers scoring high on
      burnout showed lower overall cortisol secretion on all sampling days, and a
      higher suppression of cortisol secretion after dexamethasone administration. In
      the subgroup of teachers with both high levels of perceived stress and high
      levels of burnout, a lower overall cortisol secretion was observed on the first 2
      days, with stronger increases during the first hour after awakening after
      dexamethasone suppression. This subgroup also showed the lowest self-esteem, the
      highest external locus of control, and the highest number of somatic complaints.
      CONCLUSIONS: These results demonstrate differential effects of burnout and
      perceived stress on hypothalamic-pituitary-adrenal axis regulation.

PMID- 10204974
TI  - Effect of family responsibilities and job strain on ambulatory blood pressure
      among white-collar women.
AB  - OBJECTIVE: This study was conducted to determine whether large family
      responsibilities and their combination with high job strain were associated with
      an increase in ambulatory blood pressure (BP) among white-collar women. METHODS:
      A cross-sectional study was conducted in a stratified random sample of 199 white
      collar women with or without children who were employed full time in jobs
      involving high or low strain. These women were selected from a population of 3183
      women of all ages, employed in eight organizations in Quebec City, Canada.
      Subjects wore an ambulatory BP monitor for 24 hours during a working day. Mean
      BPs were calculated. Different measures of family responsibilities were used,
      based on the number of children and their ages, and domestic work. Job strain was
      measured using the Job Content Questionnaire recommended by Karasek. RESULTS:
      Family responsibility measures were significantly related to diurnal BP among
      women holding a university degree (N=69). Indeed, women having large family
      responsibilities had increases in systolic and diastolic BPs of 2.7 to 5.7/1.8 to
      4.0 mm Hg (p< or =.05). Among women holding a university degree, increases in
      diurnal systolic and diastolic BPs reached 8.1 to 10.9/5.5 to 7.1 mm Hg (p< or
      =.01) among women having both large family responsibilities and high job strain.
      These results were independent of confounders. There was no significant
      association among women without a university degree (N=130). CONCLUSIONS: Large
      family responsibilities were associated with significant increases in diurnal
      systolic and diastolic BPs among white-collar women holding a university degree.
      In these women, the combined exposure of large family responsibilities and high
      job strain tended to have a greater effect on BP than the exposure to only one of
      these factors.

PMID- 10204975
TI  - Increased salivary cortisol reliably induced by a protein-rich midday meal.
AB  - OBJECTIVE: This study was conducted to determine whether an increase in salivary
      free cortisol would be reliably elicited by a midday meal, thus providing a
      convenient physiological challenge to the hypothalamic-pituitary-adrenal (HPA)
      axis, and whether this cortisol release depended on the protein content of the
      meal. METHOD: In healthy men, free cortisol was measured in saliva samples taken
      before and after two identical protein-rich midday meals (39% energy as protein)
      and compared with a day on which no meal was eaten. Next, in healthy women in a
      nonclinical setting, salivary cortisol was measured before and after a protein
      rich meal (32% energy as protein) on one day and a low-protein meal (5% energy as
      protein) on another day. Measures of mood, appetite, and psychological well-being
      were also taken. RESULTS: An acute meal-dependent increase in salivary cortisol
      occurred, which was reliable over 2 test days. This increase in cortisol depended
      on the proportion of protein in the meal, increasing after the high-protein but
      not the low-protein meal. The extent of this increase in cortisol correlated
      significantly with poor psychological well-being in women. Some postmeal
      improvement of mood (positive affect) was associated with the high- but not the
      low-protein meal. CONCLUSIONS: The cortisol response to meals may have
      implications for the effects of meal composition on mood, cognitive function, and
      food choice. The measurement of free cortisol in saliva provides a
      psychologically stress-free and reliable technique to assess the cortisol
      response to a standard protein-rich meal, ie, a physiological challenge to the
      HPA axis in men and women that could be investigated in naturalistic settings
      outside the laboratory.

PMID- 10204976
TI  - Impact on patients and partners of inpatient and extended cardiac counseling and
      rehabilitation: a controlled trial.
AB  - OBJECTIVES: This study evaluated the effectiveness of cardiac counseling and
      rehabilitation programs led by a nurse counselor, compared with normal care on
      outcomes for myocardial infarction (MI) patients and their partners. METHODS: A
      randomized controlled trial with follow-up to 1 year was conducted with 100
      patients recruited within 72 hours of a first MI and their partners: a Control
      group received normal care; an Inpatient group received cardiac rehabilitation
      from a nurse counselor while in hospital; and an Extended group received the same
      cardiac rehabilitation as the Inpatient group, but with additional sessions
      continuing up to 6 weeks after discharge from hospital. The scales for main
      outcome measures were 1) knowledge of heart disease and treatment (correct,
      misconceptions, and uncertainty); 2) mood (Hospital Anxiety and Depression
      Scale); 3) satisfaction; 4) disability (Functional Limitations Profile). RESULTS:
      Inpatient cardiac counseling and rehabilitation resulted in more knowledge, less
      anxiety, less depression, and greater satisfaction with care in both patients and
      partners and in less disability in patients, with effects enduring to 1 year.
      There was some evidence of additional benefit from the Extended program. Both
      nurse counselors achieved benefits on all outcome variables. CONCLUSIONS: This
      Inpatient cardiac counseling and rehabilitation program resulted in significant
      and enduring benefits of clinical value. It is likely that it would be acceptable
      to most post-MI patients, many of whom are not offered or are unable to accept
      outpatient cardiac rehabilitation.

PMID- 10204977
TI  - Gender, social support, and cardiovascular responses to stress.
AB  - OBJECTIVE: Laboratory research indicates that the presence of a supportive other
      can reduce physiological responses to a stressor. Whether there are gender
      differences, either on the part of the provider or the recipient, in this social
      support effect is explored. Such differences might shed some light on the
      frequent epidemiological reports of gender differences in social support and
      health. METHODS: Male and female subjects gave an impromptu speech and received
      either standardized supportive or nonsupportive feedback from a male or female
      confederate. Blood pressure and heart rate were monitored continuously during
      baseline and speech periods. RESULTS: Speakers with a supportive female audience
      showed a systolic increase of 25 mm Hg over baseline. Those with a nonsupportive
      female audience increased 36 mm Hg. A supportive male audience led to increases
      of 32 mm Hg, and a nonsupportive male audience 28 mm Hg. There was no significant
      effect of gender of subject. CONCLUSIONS: Results indicate that social support
      provided by women reduced cardiovascular changes for both male and female
      speakers compared with presence of a nonsupportive female audience. Social
      support from men did not. These findings suggest a possible mechanism that might
      help explain the epidemiological literature on the relationship between gender,
      social support, and health. The findings are consistent with the notion that
      married men are healthier because they marry women. Women do not profit as much
      from marriage or suffer as much from separation, in terms of health outcomes,
      because the support they gain or lose is the less effective support of a man.
      These findings render more plausible the possibility that differences in social
      support might contribute to health differences, through the dampening of
      cardiovascular responses to stress.

PMID- 10204979
TI  - Drug-related information generates placebo and nocebo responses that modify the
      drug response.
AB  - OBJECTIVE: Administration of the muscle relaxant carisoprodol and placebo was
      crossed with information that was agonistic or antagonistic to the effect of
      carisoprodol. It was investigated whether information alone induced physiological
      and psychological responses, and whether information modified the response to the
      drug. METHODS: Half of the subjects received capsules containing 525 mg
      carisoprodol together with information that the drug acted in a specific way
      (Groups Relaxant/C, Stimulant/C, and No Information/C). The other half of the
      subjects received lactose (Groups Relaxant/L, Stimulant/L, and No Information/L).
      Dependent variables were blink reflexes and skin conductance responses,
      subjective measures of tension and sleepiness, and serum carisoprodol and
      meprobamate concentrations. Recordings were made between 15 and 130 minutes after
      administration of the capsules. RESULTS: The Stimulant/L group reported more
      tension compared with the other two groups, and carisoprodol increased tension
      even more in the Stimulant/C group. The Relaxant/C group displayed higher levels
      of carisoprodol serum concentration compared with the other groups that received
      carisoprodol. CONCLUSIONS: Reported tension was modulated in the direction
      suggested by the stimulant information. The effect of carisoprodol on tension was
      also modulated by stimulant information. Increased carisoprodol absorption in the
      group that received relaxant information could be a mechanism in the placebo
      response.

PMID- 10204978
TI  - Longitudinal association of cardiovascular reactivity and blood pressure in
      Samoan adolescents.
AB  - OBJECTIVE: The longitudinal association between blood pressure (BP) reactivity to
      a video game and resting BP 3 to 4 years later was investigated in 83 Samoan
      adolescents from American and (Western) Samoa as part of a multidisciplinary
      study of cardiovascular disease (CVD) risk in modern Samoans. METHODS:
      Participants ranged in age from 11 to 14 years at baseline, in 1992 to 1993, and
      14 to 18 years at follow-up in 1996. Video game BP reactivity was defined as the
      residual score of the regression of the maximum BP during the video game on the
      minimum resting BP before the video game. The predictive effect of baseline video
      game BP reactivity on follow-up resting BP was tested using regression models
      with baseline resting BP, baseline body mass index (BMI), and age as covariates.
      RESULTS: Systolic BP reactivity to the video game at baseline was significantly,
      p=.04, and independently associated with resting systolic BP 3 to 4 years later.
      Samoan adolescents who had higher systolic BP reactivity scores at baseline had
      significantly higher resting systolic BP at follow-up after adjustment for the
      significant effects of baseline resting systolic BP, age, and BMI. There were no
      interactions between sex and reactivity or between residence, American Samoa or
      (Western) Samoa, and reactivity in the models, indicating that the effects of
      systolic BP reactivity in early adolescence on later adolescent resting systolic
      BP were similar in the entire study sample. CONCLUSIONS: Video game
      cardiovascular reactivity seems to assess aspects of psychophysiological arousal
      and prospective CVD risk in Samoan adolescents of both sexes residing in both
      Samoas, and may be useful for understanding the role of psychosocial stress and
      health in modernizing societies.

PMID- 10204980
TI  - Sociosomatics gives insights into functional disorders.

PMID- 10204981
TI  - Sociosomatics and illness in CFS.

PMID- 10204982
TI  - Evaluation of several techniques to modify denatured muscle tissue to obtain a
      scaffold for peripheral nerve regeneration.
AB  - The aim of this study was to (1) evaluate the effect of several preparation
      techniques of denatured muscle tissue to obtain an open three-dimensional
      structure, and (2) test if this scaffold is suitable for peripheral nerve
      regeneration. Four samples (A-D) of muscle tissue specimens were evaluated using
      light microscopy, immunohistochemistry and cryo-scanning electron microscopy.
      Sample C showed the most open extracellular matrix, whilst collagen type IV and
      laminin (in the basal lamina) could still be observed using immunohistochemistry.
      An in vivo pilot study showed that the first signs of functional nerve recovery
      and axon regeneration could be observed after 3 weeks of implantation. We
      conclude that sample C has the most open structure and leads to good nerve
      regeneration and functional nerve recovery.

PMID- 10204984
TI  - Absence of muscle regeneration after implantation of a collagen matrix seeded
      with myoblasts.
AB  - Collagens are widely used as biomaterials for e.g. soft tissue reconstruction.
      The present study was aimed at reconstruction of abdominal wall muscle using
      processed dermal sheep collagen (DSC) and myoblast seeding. Myoblasts were
      harvested from foetal quadriceps muscle of an inbred rat strain, cultured, seeded
      as non-differentiated cells into DSC-discs and incubated in vitro for 2 h. The
      discs were implanted in the abdominal wall defects in adult rats. Non-seeded
      discs functioned as control. Implantation periods till week 6 were chosen. At day
      1 and 2 after implantation infiltration of granulocytes and macrophages was
      clearly more intense in the seeded discs than in the controls. Relatively large
      numbers of mast cells infiltrated from the side of the adhering omentum. In
      central areas of the discs, seeded cells were easily recognized till day 5, since
      non-seeded control discs did not contain such cells. Ingrowth of host cells and
      tissue at the margins proceeded faster with the seeded discs. Lymphocyte
      accumulations were observed in the 3 week seeded specimen. At week 3 and week 6,
      in the seeded discs muscle tissue was not present, in contrast to very large
      giant-like cells. It is concluded that the chosen method of myoblast seeding did
      not result in the regeneration of muscle during this observation period.
      Unfavorable circumstances such as humoral factors, direct cellular interactions
      (phagocytosis), indirect cellular interactions (cytokines), or initial absence of
      vascularization, may play a role. Further studies are required.

PMID- 10204983
TI  - Study on gelatin-containing artificial skin: I. Preparation and characteristics
      of novel gelatin-alginate sponge.
AB  - An absorbable sponge, composed of gelatin and alginate, was prepared by new
      crosslinking method that improved the efficiency of crosslinking. The
      crosslinking degree was characterized by trinitrobenzenesulfonic acid (TNBS)
      assay. A water uptake ability test, in vitro drug release and collagenase
      degradation tests, and an in vivo animal test were employed to confirm the
      applicability of this gelatin-alginate sponge as a wound dressing material. As
      the alginate content in the sponge increased, the porosity increased, resulting
      in an enhanced water uptake ability. Sponges loaded with silver sulfadiazine or
      gentamicin sulfate slowly released drugs for up to four days. The crosslinked
      sponge resisted in vitro collagenase digestion for up to three days. An in vivo
      animal test using witar rat showed rather good wound healing effect of gelatin
      alginate sponge containing AgSD than vaseline gauze in our full-thickness skin
      defect model.

PMID- 10204985
TI  - Hydrolysis of alpha-tricalcium phosphate in NaF solutions.
AB  - Controlling the incorporation of Na and fluoride in apatite-based dental
      restoratives and analogs of bone formed under physiologic conditions may be
      desirable in controlling their long-term in vivo responses. Formation of these
      analogs was investigated. Hydrolysis of alpha-tricalcium phosphate (alpha-TCP)
      was carried out at physiologic temperature in NaF solutions and the solids
      product(s) were analyzed. alpha-TCP hydrolysis was complete within 48 h and the
      only solid products identified were apatites. Changes in solution chemistry were
      determined at 48 h and 4 weeks. Na and Ca concentrations were determined by
      spectrometric methods, P and F concentrations were determined by ion
      chromatography; pH values were obtained. The extent of fluoride and sodium
      incorporation in the apatites formed varied depending on the NaF concentration of
      the solution. Both increased with increasing NaF concentration. Apatite
      compositions ranged from Ca9.06(HPO4)0.94(PO4)5.06OH1.06 for hydrolysis in water
      to Ca9.28Na0.56(HPO4)(x)(PO4)(6-x)F0.920Hy for hydrolysis in 0.1 M NaF solution.
      The proportions of PO4, HPO4 and OH in Na- and F-containing apatites are
      indeterminate but obey the equation (y = constant+x). The (Ca+Na)/P ratio of the
      apatite formed by alpha-TCP hydrolysis in 0.1M NaF approaches 1.67 indicating the
      vacant Ca sites become almost completely filled by the Na ions. The surface areas
      of these apatites initially remain constant with increasing NaF concentrations;
      at elevated concentrations apatite surface areas decrease with increasing NaF
      concentration. This is consistent with the removal of Na from solution by its
      incorporation in the apatites, not by its adsorption onto their surfaces.

PMID- 10204986
TI  - The water uptake of poly(tetrahydrofurfuryl methacrylate).
AB  - Poly(tetrahydrofurfuryl methacrylate) possesses some unique characteristics with
      respect to its biocompatibility and behaviour in water. The water uptake is high
      (>70%) and very slow (over 3 yr), but the material remains rigid throughout the
      process. The mechanism behind the uptake is in two stages; an initial Fickian
      stage, then as the matrix approaches saturation (about 3 wt%) a second clustering
      mechanism takes over. The rate of uptake of the second stage of the uptake is
      controlled by creep (or stress relaxation), and the chemical potential driving
      the uptake from clustering of the furfuryl rings of the polymer. If clustering or
      the creep is prevented (by appropriate co-polymerisation) the polymer behaves in
      an ideal, Fickian manner.

PMID- 10204987
TI  - Dissolution/reprecipitation of calcium phosphate thin films produced by ion beam
      sputter deposition technique.
AB  - The dissolution, reprecipitation and protein adsorption properties of amorphous
      CaP bioceramic thin films produced with an ion beam sputter deposition technique
      using hydroxyapatite (HA) and fluorapatite (FA) as starting materials were
      studied using Fourier transform infrared spectroscopy (FTIR) with attenuated
      total internal reflectance (ATR). Our studies showed that these amorphous CaP
      coatings dissolved to a greater extent when exposed to bovine serum albumin (BSA)
      in saline solution when compared to a protein free saline solution. Analysis of
      changes in infrared spectra revealed that coatings exposed to BSA solution
      exhibited a higher degree of crystalline structure after
      dissolution/reprecipitation than those exposed to saline alone. There was the
      indication that the association of inorganic and organic contents was achieved on
      the coating surface in BSA solution. We could detect no significant difference
      between the coatings produced from HA and FA targets.

PMID- 10204988
TI  - Modified acrylic bone cement with high amounts of ethoxytriethyleneglycol
      methacrylate.
AB  - One cause of arthroplasty failure is the brittle mechanical behavior of bone
      cements. However, the improvement of cement formulations must also be accompanied
      by the maintenance of a wide variety of characteristics. New bone cements were
      obtained by the substitution of high percentages, up to 60% (v/v), of methyl
      methacrylate (MMA) by a higher molecular weight and more hydrophilic monomer,
      ethoxytriethyleneglycol methacrylate (TEG). The essential advantages of these
      materials were the decrease of maximum temperature together with a decrease in
      the residual monomer content with respect to conventional cement formulations.
      The water absorption process obeyed diffusion laws and the equilibrium water
      content increased by the introduction of higher percentages of the hydrophilic
      component. This characteristic had an appreciable effect on the viscoelastic
      behavior analyzed by DMTA. These modified bone cements had reduced polymerization
      shrinkage and similar levels of porosity. Tensile test revealed that the
      introduction of TEGMA gave rise to an important modification of the mechanical
      behavior, with a noticeable increase in the fracture strain. This fact was also
      confirmed by means of the analysis of the fracture surfaces by SEM.

PMID- 10204990
TI  - Preparation of a biphasic porous bioceramic by heating bovine cancellous bone
      with Na4P2O7.10H2O addition.
AB  - Sintered bovine cancellous bone exhibited excellent biocompatiblity, high
      porosity and have an interconnecting porous structure allowing for bone ingrowth.
      However, the main mineral constitution of sintered bovine bone-hydroxyapatite
      (Ca10(PO4)6(OH)2, HAP) seems to be too stable in vivo. For improving its
      bioactivity, the calcined bovine bone removing the organic substance by burning
      process-with different quantities of sodium pyrophosphate (Na4P2O7.10H2O, NP)
      addition was heated to a high temperature to transform its crystalline phase
      constitution from HAP into TCP/HAP biphasic or other multiphasic structures.
      Results revealed that the calcined bovine bone without NP addition, exhibited a
      pure form of HAP characterized pattern during heating. Its thermal behavior was
      similar to stoichiometric HAP, it gradually lost its OH- ions and transformed
      into oxyhydroxyapatite at high temperature. After being doped into calcined
      bovine bone, NP would react with HAP to form betaBTCP and NaCaPO4 around 600
      degrees C. At 900 degrees C, doped NP would completely react with HAP and the
      NaCaPO4 would further react with HAP to form more betaBTCP in the system. With NP
      increasing in the calcined bovine bone, HAP would gradually convert into
      different crystalline phase compositions of TCP/HAP, TCP/HAP/NaCaPO4 or
      TCP/NaCaPO4 at high temperature. By heating calcined bovine cancellouse bone with
      different quantities of NP we could obtain different crystalline phase
      compositions of natural porous bioceramic in this study.

PMID- 10204989
TI  - Influence of the modification of P/L ratio on a new formulation of acrylic bone
      cement.
AB  - The use of smaller powder/liquid (P/L) ratio favours the handling and wetting of
      poly(methyl methacrylate) (PMMA) beads in bone cement formulations. In this paper
      a P/L ratio of 1.86 is tested to overcome adhesion problems found in
      hydroxypropyl methacrylate (HPMA) modified bone cements and the influence on bone
      cement characteristics was analysed. The reduction of the P/L ratio leads to
      higher temperature peaks and shorter setting times, whereas the residual monomer
      content increases slightly. Water uptake obeys the diffusion laws, and the
      introduction of a more hydrophilic monomer gives rise to an increase of this
      parameter, which does not present significant changes with modification of the
      P/L ratio. Polymerization shrinkage is slightly greater because of the
      introduction of higher proportions of monomer in the formulation. Mechanical
      properties are similar to those obtained with conventional P/L ratios. The
      analysis of scanning electron microscopy (SEM) reveals an improvement of the
      adhesion between phases with respect to P/L = 2 formulations.

PMID- 10204991
TI  - A microscopical evaluation of 24 retrieved failed hollow implants.
AB  - Twenty-four hollow ITI implants (four screws, and 20 cylinders) were retrieved
      because of failure, and evaluated in our laboratory, in a eight-year period (1989
      1996), to see if a common cause could be observed in this implant design. No
      selection of these implants was carried out, and they represented the total
      number of implants of this type received in the above-mentioned time frame. The
      implants had been inserted by several different clinicians and were received from
      four universities and a private practice. The implants had been removed for
      mobility, pain, and presence of a vertical bone loss. About two-thirds of the
      implants were unstable in the jaw at the time of retrieval. Twenty implants had
      been used as single implants restoration and four in bridge reconstructions. Most
      of our specimens showed that the inflammatory process had reached the hollow
      portion of the implants. The following microscopical features were present in
      almost all our specimens: calculus and plaque on the coronal portion of the
      implant surface, presence of proliferating epithelium and of bone sequestra, and
      presence of bone apically to the inflammatory process. Perhaps, when the
      inflammatory process reaches the implant hollow portion, the infection runs a
      more rapid course due to the scarce vascularity of the bone inside this part.

PMID- 10204992
TI  - The effect of heat treatment on bone-bonding ability of alkali-treated titanium.
AB  - The purpose of this study was to evaluate the bone-bonding ability of alkali
      treated titanium with and without heat treatment. Three groups of smooth titanium
      plate were prepared: control, or pure titanium, alkali-treated titanium, and
      alkali- and heat-treated titanium. The plates were inserted transcortically into
      the proximal metaphyses of bilateral rabbit tibiae. The tensile failure loads
      between implants and bones were measured at two time intervals using a detaching
      test. The tensile failure loads of the alkali- and heat-treated titanium group
      were 2.71 and 4.13 kgf, at 8 and 16 weeks, respectively, and significantly higher
      than those of the other titanium groups. Histological examination revealed that
      alkali- and heat-treated titanium was in direct contact with bone, but the other
      titanium groups had a thin intervening fibrous tissue. This result indicated that
      the alkali-treated titanium without heat treatment had no bone-bonding ability
      due to the unstable reactive surface layer of alkali-treated titanium. In
      conclusion, both alkali and heat treatment are essential for preparing bioactive
      titanium and this bioactive titanium is thought to be useful for orthopedic
      implants with cementless fixation.

PMID- 10204993
TI  - Identification of glucoside and carboxyl-linked glucuronide conjugates of
      mycophenolic acid in plasma of transplant recipients treated with mycophenolate
      mofetil.
AB  - 1. Mycophenolic acid (MPA), is primarily metabolized in the liver to 7-O-MPA-beta
      glucuronide (MPAG). Using RP-h.p.l.c. we observed three further MPA metabolites,
      M-1, M-2, M-3, in plasma of transplant recipients on MMF therapy. To obtain
      information on the structure and source of these metabolites: (A) h.p.l.c.
      fractions containing either metabolite or MPA were collected and analysed by
      tandem mass spectrometry; (B) the metabolism of MPA was studied in human liver
      microsomes in the presence of UDP-glucuronic acid, UDP-glucose or NADPH; (C)
      hydrolysis of metabolites was investigated using beta-glucosidase, beta
      glucuronidase or NaOH; (D) cross-reactivity of each metabolite was tested in an
      immunoassay for MPA (EMIT). 2. Mass spectrometry of M-1, M-2, MPA and MPAG in the
      negative ion mode revealed molecular ions of m/z 481, m/z 495, m/z 319 and m/z
      495 respectively. 3. Incubation of microsomes with MPA and UDP-glucose produced M
      1, with MPA and UDP-glucuronic acid MPAG and M-2 were formed, while with MPA and
      NADPH, M-3 was observed. 4. Beta-Glucosidase hydrolysed M-1 completely. Beta
      Glucuronidase treatment led to a complete disappearance of MPAG whereas the
      amount of M-2 was reduced by approximately 30%. Only M-2 was labile to alkaline
      treatment. 5. M-2 and MPA but not M-1 and MPAG cross-reacted in the EMIT assay.
      6. These results suggest that: (i) M-1 is the 7-OH glucose conjugate of MPA; (ii)
      M-2 is the acyl glucuronide conjugate of MPA; (iii) M-3 is derived from the
      hepatic CYP450 system.

PMID- 10204994
TI  - Pharmacological characterization of the bradykinin B2 receptor: inter-species
      variability and dissociation between binding and functional responses.
AB  - 1. The present study addresses the differences in binding profiles and functional
      properties of the human and rat bradykinin (BK) B2 receptor using various kinin
      receptor peptide derivatives as well as the non-peptide receptor antagonists WIN
      64338 (phosphonium, [[4-[[2-[[bis(cyclohexylamino)methylene]amino]-3-(2
      naphtalenyl)1- oxopropyl]amino]-phenyl]-methyl]tributyl, chloride, monohydro
      chloride), and FR173657 (E)-3-(6-acetamido-3-pyridyl)-N-[-N-[2,4-dichloro-3-[(2
      methyl-8-quinoli nyl)oxymethyl]-phenyl]N-methylamino carbonyl methyl] acrylamide.
      2. [3H]-BK bound with a similar affinity to membranes of Chinese hamster ovary
      cells (CHO-K1) expressing the cloned human (hB2-CHO) or rat (rB2-CHO) B2
      receptor, human embryonic intestine cells (INT407) expressing the native B2
      receptor, human umbilical vein (HUV) and rat uterus (RU). WIN 64338 and FR173657
      bound with a 3.8-6.6 fold and 7.0-16.3 fold higher affinity the rat than the
      human B2 receptor, respectively. The affinity values of BK derivatives as well as
      non-peptide antagonists were reduced by 6-23 fold in physiological HBSS compared
      to low ionic strength TES binding buffer. 3. BK (0.01-3000 nM) increased inositol
      triphosphates (IP3) levels in hB2-CHO, rB2-CHO and INT407 cells. The B2 receptor
      antagonist, Hoe 140 (D-Arg0-[ Hyp3, Thi5, D-Tic7, Oic8]-BK) at 10(-7) M,
      significantly shifted to the right the IP3 response curves to BK giving apparent
      pKB values of 8.56, 9.79 and 8.84 for hB2-CHO, rB2-CHO and INT407 cells,
      respectively. 4. In human isolated umbilical vein, Hoe 140, D-Arg0-[Hyp3, D-Phe7,
      Leu8]-BK and NPC 567 had a lower potency in functional assays (pKB 8.18, 5.77 and
      5.60, respectively) than expected from their affinity in binding studies (pKi
      10.52, 8.64 and 8.27, respectively). 5. FR173657 behaved as a high affinity
      ligand with pKi values of 8.59 and 9.81 and potent competitive antagonist with
      pKB values of 7.80 and 8.17 in HUV and RU, respectively. FR173657 bound with a
      similar affinity the cloned and native bradykinin B2 receptor in human (pKi of
      8.66 and 8.59, respectively) and in rat (pKi 9.67 and 9.81, respectively). 6. In
      conclusion, we suggest that the binding buffer composition has to be taken into
      account when screening new compounds and that inter-species differences should be
      considered when setting up animal models with the aim of developing bradykinin B2
      receptor antagonists as therapeutic agents.

PMID- 10204995
TI  - Lung clearance of intratracheally instilled 99mTc-tobramycin using pulmonary
      surfactant as vehicle.
AB  - 1. The use of pulmonary exogenous surfactant as a vehicle for intratracheally
      administered antibiotics to improve local antimicrobial therapy has been
      proposed. The present study investigated lung clearance rates in the rat of
      intratracheally instilled technetium labelled tobramycin with and without the
      addition of surfactant to the antibiotic solution. 2. The influence of surfactant
      on 99mTc-tobramycin lung clearance rates was studied dynamically with a gamma
      camera in anaesthetized spontaneously breathing animals and in mechanically
      ventilated animals. 3. The results show that instillation of 99mTc-tobramycin
      with use of surfactant as vehicle significantly increases 99mTc-tobramycin lung
      clearance compared to instillation of 99mTc-tobramycin solution alone (P=0.006
      between the two spontaneously breathing groups of animals and P=0.02 between the
      two ventilated groups of animals, ANOVA for repeated time measurements). The half
      life (t1/2) of composite clearance curves in spontaneous breathing animals was
      147 min for animals receiving 99mTc-tobramycin versus 61 min for animals
      receiving 99mTc-tobramycin with surfactant. In mechanically ventilated animals
      this was 163 min versus 51 min, respectively. 4. It is concluded that exogenous
      surfactant, used as vehicle for intratracheally instilled 99mTc-tobramycin,
      increases lung clearance rate of 99mTc-tobramycin in rats.

PMID- 10204996
TI  - Inverse agonist abolishes desensitization of a constitutively active mutant of
      thyrotropin-releasing hormone receptor: role of cellular calcium and protein
      kinase C.
AB  - 1. C335Stop is a constitutively active mutant of the TRH receptor (TRH-R). To
      investigate the mechanism of the decreased responsiveness of C335Stop TRH-R, we
      studied cellular Ca2+ concentrations ([Ca2+]i) in AtT20 cells stably transfected
      with C335Stop TRH-R cDNA, or Ca2+-activated chloride currents in Xenopus laevis
      oocytes expressing this mutant receptor after injection of cRNA. The competitive
      TRH-R binding antagonist, chlorodiazepoxide (CDE), was used as an inverse agonist
      to study the contribution of constitutive activity to desensitization. 2. Acute
      treatment with CDE resulted in a rapid (within minutes) decrease in [Ca2+]i and
      an increase in the response amplitude to TRH with no measurable change in
      receptor density. Conversely, removal of chronically administered CDE caused a
      rapid increase in [Ca2+]i and a decrease in TRH response amplitude. 3. CDE
      abolished heterologous desensitization induced by C335Stop TRH-R on muscarinic m1
      receptor (ml-R) co-expressed in Xenopus oocytes. 4. Chelation of extracellular
      calcium with EGTA caused a rapid decrease in [Ca2+]i and a concomitant increase
      in the response to TRH in AtT20 cells expressing C335Stop TRH-Rs. 5.
      Chelerythrine, a specific inhibitor of protein kinase C (PKC), reversed the
      heterologous desensitization of the response to acetylcholine (ACh). The
      phosphoserine/phosphothreonine phosphatase inhibitor, okadaic acid, abolished the
      effect of chelerythrine. 6. Down-regulation of PKC by chronic exposure to phorbol
      12-myristate 13-acetate (PMA) or acute inhibition with chelerythrine caused a
      partial resensitization of the response to TRH. 7. Western analysis indicated
      that the alpha subtype of protein kinase C was down-regulated in cells expressing
      C335Stop TRH-Rs. Following a 5 min exposure to PMA, the residual alphaPKC
      translocated to the particular fraction. 8. We propose that cells expressing the
      constitutively active mutant TRH-R rapidly desensitize their response, utilizing
      a mechanism mediated by an increase in [Ca2+]i and PKC.

PMID- 10204998
TI  - Electrophysiological studies on the postnatal development of the spinal
      antinociceptive effects of the delta opioid receptor agonist DPDPE in the rat.
AB  - 1. The antinociceptive effects of the delta opioid receptor selective agonist,
      DPDPE [(D-Pen2,D-Pen5)-enkephalin] was studied in rats aged postnatal day (P) 14,
      P21, P28 and P56. 2. Antinociceptive effects of DPDPE were measured as percentage
      inhibition of the C-fibre evoked response and post-discharge of dorsal horn
      neurones evoked by peripheral electrical stimulation. DPDPE was administered by
      topical application, akin to intrathecal injection. 3. DPDPE (0.1-100 microg)
      produced dose-related inhibitions at all ages; these inhibitions were reversed by
      5 microg of the opioid antagonist naloxone. 4. The dose-response curves for C
      fibre evoked response and post-discharge of the neurones were not different in
      rats aged P14 and P21. DPDPE was significantly more potent at P14 and P21
      compared with its inhibitory effects on these responses at P28 and P56. 5. DPDPE
      produced minor inhibitions of the A-fibre evoked response of the neurones at P14,
      P21, P28 and P56, suggesting that the inhibitory effects of DPDPE are mediated
      via presynaptic receptors on the terminals of C-fibre afferents. 6. Since spinal
      delta opioid receptor density changes little over this period, the increased
      antinociceptive potency of DPDPE in the rat pups compared with the adult is
      likely to be due to post-receptor events, or in developmental changes in the
      actions of other transmitter/receptor systems within the spinal cord.

PMID- 10204997
TI  - Activation of three types of voltage-independent Ca2+ channel in A7r5 cells by
      endothelin-1 as revealed by a novel Ca2+ channel blocker LOE 908.
AB  - 1. We have shown that in addition to voltage-operated Ca2+ channel (VOC),
      endothelin-1 (ET-1) activates two types of Ca2+-permeable nonselective cation
      channel (NSCC) in A7r5 cells: its lower concentrations (< or = 1 nM; lower [ET
      1]) activate only an SK&F 96365-resistant channel (NSCC-1), whereas its higher
      concentrations (> or = 10 nM; higher [ET-1]) activate an SK&F 96365-sensitive
      channel (NSCC-2) as well. 2. We now characterized the effects of a blocker of
      Ca2+ entry channel LOE 908 on NSCCs and store-operated Ca2+ channel (SOCC) in
      A7r5 cells, and using two drugs, clarified the involvement of these channels in
      the ET-1-induced increase in the intracellular free Ca2+ concentrations
      ([Ca2+]i). Whole-cell recordings and [Ca2+]i monitoring with fluo-3 were used. 3.
      LOE 908 up to 10 microM had no effect on increases in [Ca2+]i induced by
      thapsigargin or ionomycin, but SK&F 96365 abolished them. 4. In the cells clamped
      at -60 mV, both lower and higher [ET-1] induced inward currents with linear iv
      relationships and the reversal potentials of -15.0 mV. Thapsigargin induced no
      currents. 5. In the presence of nifedipine, lower [ET-1] induced a sustained
      increase in [Ca2+]i, whereas higher [ET-1] induced a transient peak and a
      sustained increase. The sustained increases by lower and higher [ET-1] were
      abolished by removal of extracellular Ca2+, and they were suppressed by LOE 908
      to 0 and 35%, respectively, with the LOE 908-resistant part being abolished by
      SK&F 96365. 6. These results show that LOE 908 is a blocker of NSCCs without
      effect on SOCC, and that the increase in [Ca2+]i at lower [ET-1] results from
      Ca2+ entry through NSCC-1 in addition to VOC, whereas the increase at higher [ET
      1] involves NSCC-1, NSCC-2 and SOCC in addition to VOC.

PMID- 10204999
TI  - Inhibition of GABA-gated chloride channels by 12,14-dichlorodehydroabietic acid
      in mammalian brain.
AB  - 1. 12,14-dichlorodehydroabietic acid (12,14-Cl2DHA) reduced GABA-stimulated
      uptake of 36Cl- into mouse brain synaptoneurosomes suggesting inhibition of
      mammalian GABA(A) receptor function. 2. 12,14-Cl2DHA did not affect the binding
      of [3H]-muscimol to brain membranes but displaced specifically bound [3H]-EBOB.
      The inhibitory effect on [3H]-EBOB binding was not reversible. 12,14-Cl2DHA
      reduced the availability of [3H]-EBOB binding sites (Bmax) without changing the
      KD of the radioligand for remaining sites. 12,14-Cl2DHA did not affect the rate
      of association of [3H]-EBOB with its chloride channel receptor, but increased the
      initial rate of [3H]-EBOB dissociation. 3. 12,14-Cl2DHA enhanced the incidence of
      EPSCs when rapidly applied to cultured rat cortical neurones. Longer exposures
      produced block of IPSCs with marked increases in the frequency of EPSCs and min
      EPSCs. 12,14-Cl2DHA also irreversibly suppressed chloride currents evoked by
      pulses of exogenous GABA in these cells. 4. Ultimately, 12,14-Cl2DHA inhibited
      all synaptic traffic and action currents in current clamped cells indicating
      that, in contrast to picrotoxinin (which causes paroxysmal bursting), it is not
      fully selective for the GABA(A) receptor-chloride channel complex. 5. The
      depolarizing block seen with 12,14-Cl2DHA in amphotericin-perforated preparations
      implicates loss of Ca2+ buffering in the polarity change and this may account for
      inhibition of spontaneous action potentials. 6. Our investigation demonstrates
      that 12,14-Cl2DHA blocks GABA-dependent chloride entry in mammalian brain and
      operates as a non-competitive insurmountable GABA(A) antagonist. The mechanism
      likely involves either irreversible binding of 12,14-Cl2DHA to the
      trioxabicyclooctane recognition site or a site that is allosterically coupled to
      it. We cannot exclude, however, the possibility that 12,14-Cl2DHA causes
      localized proteolysis or more extensive conformational change within a critical
      subunit of the chloride channel.

PMID- 10205000
TI  - Contractile effects by intracellular angiotensin II via receptors with a distinct
      pharmacological profile in rat aorta.
AB  - 1. We studied the effect of intracellular angiotensin II (Ang II) and related
      peptides on rat aortic contraction, whether this effect is pharmacologically
      distinguishable from that induced by extracellular stimulation, and determined
      the Ca2+ source involved. 2. Compounds were delivered into the cytoplasm of de
      endothelized aorta rings using multilamellar liposomes. Contractions were
      normalized to the maximum obtained with phenylephrine (10(-5) M). 3.
      Intracellular administration of Ang II (incorporation range: 0.01-300 nmol mg(
      1)) resulted in a dose-dependent contraction, insensitive to extracellular
      administration (10(-6) M) of the AT1 receptor antagonist CV11947, the AT2
      receptor antagonist PD 123319, or the non-selective AT receptor antagonist and
      partial agonist saralasin ([Sar1,Val5,Ala8]-Ang II (P<0.05). 4. Intracellular
      administration of CV11947 or PD 123319 right shifted the dose-response curve
      about 1000 fold or 20 fold, respectively. PD 123319 was only effective if less
      than 30 nmol mg(-1) Ang II was incorporated. 5. Contraction was partially
      desensitized to a second intracellular Ang II addition after 45 min (P<0.05). 6.
      Intracellular administration of Ang I and saralasin also induced contraction
      (P<0.05). Both responses were sensitive to intracellular CV11947 (P<0.05), but
      insensitive to PD 123319. The response to Ang I was independent of intracellular
      captopril. 7. Contraction induced by extracellular application of Ang II and of
      Ang I was abolished by extracellular pre-treatment with saralasin or CV11947
      (P<0.05), but not with PD 123319. Extracellular saralasin induced no contraction.
      8. Intracellular Ang II induced contraction was not affected by pre-treatment
      with heparin filled liposomes, but completely abolished in Ca2+-free external
      medium. 9. These results support the existence of an intracellular binding site
      for Ang II in rat aorta. Intracellular stimulation induces contraction dependent
      on Ca2+-influx but not on Ins(1,4,5)P3 mediated release from intracellular Ca2+
      stores. Intracellular Ang I and saralasin induce contraction, possibly via the
      same binding site. Pharmacological properties of this putative intracellular
      receptor are clearly different from extracellular stimulated AT1 receptors or
      intracellular angiotensin receptors postulated in other tissue.

PMID- 10205001
TI  - Protective effect of cyclosporin A and FK506 from nitric oxide-dependent
      apoptosis in activated macrophages.
AB  - 1. Activation of macrophages with lipopolysaccharide (LPS) and low doses of
      interferon-gamma (IFN-gamma) induced apoptotic death through a nitric oxide
      dependent pathway. 2. Treatment of cells with the immunosuppressors cyclosporin A
      (CsA) or FK506 inhibited the activation-dependent apoptosis. 3. These drugs
      decreased the up-regulation of p53 and Bax characteristic of activated
      macrophages. Moreover, incubation of activated macrophages with CsA and FK506
      contributed to maintain higher levels of Bcl-2 than in LPS/IFN-gamma treated
      cells. 4. The inhibition of apoptosis exerted by CsA and FK506 in macrophages was
      also observed when cell death was induced by treatment with chemical nitric oxide
      donors. 5. Incubation of macrophages with LPS/IFN-gamma barely affected caspase-1
      but promoted an important activation of caspase-3. Both CsA and FK506 inhibited
      pathways leading to caspase-3 activation. Moreover, the cleavage of poly(ADP
      ribose) polymerase, a well established caspase substrate, was reduced by these
      immunosuppressive drugs. 6. CsA and FK506 reduced the release of cytochrome c to
      the cytosol and the activation of caspase-3 in cells treated with nitric oxide
      donors. 7. These results indicate that CsA and FK506 protect macrophages from
      nitric oxide-dependent apoptosis and suggest a contribution of the macrophage to
      innate immunity under conditions of immunosuppression of the host.

PMID- 10205002
TI  - Pharmacological activities of TEI-8362, a novel inhibitor of human neutrophil
      elastase.
AB  - 1. TEI-8362, 4-(N-(3-((3-carboxypropyl)amino)-8-methyl-1-oxo-4-azaisochromen-6-
      yl)carbamoyl)-4-((phenylmethoxy)carbonylamino)butanoic acid (C26H28N4O9) is a
      novel inhibitor of human neutrophil elastase (HNE). We evaluated its
      pharmacological profile in vitro and in vivo. 2. TEI-8362 demonstrated potent
      inhibition of HNE with a Ki value of 1.38 x 10(-9) M. Its selectivity for HNE
      among a variety of proteases ranged from 163 fold to 68,000 fold in favour of
      HNE. 3. The pulmonary haemorrhage that occurred after i.t. instillation of HNE to
      hamsters was inhibited by either i.t., i.v., or inhalant administration of TEI
      8362. 4. Intratracheal administration of lipopolysaccharide induced pulmonary
      neutrophilia. Twenty-four hours after lipopolysaccharide administration, the
      additional treatment with formyl-methionyl-leucyl-phenylalanine resulted in a
      specific neutrophil-dependent acute lung injury. In this model, lung injury was
      significantly attenuated by i.t., i.v., or inhalant administration of TEI-8362.
      5. These pharmacological actions of TEI-8362 suggest that this drug has
      therapeutic value in the treatment of destructive lung diseases due to
      neutrophils.

PMID- 10205003
TI  - Effects of propafenone on K currents in human atrial myocytes.
AB  - 1. The class Ic anti-arrhythmic agent, flecainide is known to inhibit the
      transient outward K current (Ito) selectively in human atrium. We studied the
      effects of propafenone, another class Ic antiarrhythmic agent, on K currents in
      human atrial myocytes using a whole-cell voltage-clamp method. 2. Propafenone
      inhibited both Ito and the sustained or ultra-rapid delayed rectifier K current
      (Isus or Ikur) evoked by depolarization pulses. The concentration for half
      maximal inhibition (IC50) was 4.9 microM for Ito and 8.6 microM for Isus.
      Propafenone blocked Ito and Isus in a voltage- and use-independent fashion and
      accelerated the inactivation time constant of Ito [from 28.3 to 6.7 ms at 10
      microM propafenone]. 3. The steady-state inactivation curve for Ito was
      unaffected by propafenone. Propafenone did not affect the initial current at
      depolarizing potentials, but it did produce a block that increased as a function
      of time after depolarization (time constant of 3.4 ms). This suggests that
      propafenone preferentially blocked Ito in the open state. 4. Propafenone had no
      significant effect on the rate at which Ito recovered from inactivation at -80 mV
      suggesting that propafenone dissociates rapidly from the channel. 5. The steady
      state activation curve for Isus was not affected by propafenone. Propafenone
      slowed the time course of the onset of the Isus tail current. This suggests that
      propafenone blocked Isus in the open state. 6. The present results suggest that,
      unlike flecainide, propafenone blocks both Ito and Isus in human atrial myocytes
      in the open state at clinically relevant concentrations.

PMID- 10205005
TI  - The vasoconstrictor effect of 8-epi prostaglandin F2alpha in the hypoxic rat
      heart.
AB  - 1. 8-epi prostaglandin (PG) F2alpha, a vasoconstrictor isoprostane, is
      synthesized under conditions of oxidative stress. This study was undertaken to
      investigate the vasoconstrictor effect of 8-epi PGF2alpha in the coronary
      circulation before and after a period of oxidative stress. 2. The effects of the
      isoprostane 8-epi PGF2alpha and the thromboxane mimetic U46619 were compared in
      the isolated rat heart perfused in the Langendorff mode at a constant pressure of
      80 mmHg. 3. In normal hearts U46619 caused a dose-related reduction in coronary
      flow (ED50 4.7+/-2.2 nmol). In contrast, 8-epi PGF2alpha had no effect. 4. After
      reducing perfusion pressure to 20 mmHg for 30 min and reperfusing at 80 mmHg, the
      dose-response curve to U46619 was unaffected. In contrast, 8-epi PGF2alpha caused
      a dose-dependent drop in coronary flow (ED50 52.6+/-12.7 nmol), producing a
      similar maximal reduction to U46619. 5. Similarly, after perfusion with xanthine
      and xanthine oxidase for either 15 or 30 min there was little change in the
      response to U46619 in comparison to control hearts. In contrast, 8-epi PGF2alpha
      caused a reduction in coronary flow similar to that produced by U46619, the
      magnitude of the response being related to the length of xanthine/xanthine
      oxidase perfusion. 6. Responses to both U46619 and 8-epi PGF2alpha after
      xanthine/xanthine oxidase perfusion were blocked by the selective thromboxane
      receptor antagonist SQ29548 10(-7) M. 7. These results show that oxidative stress
      in the isolated perfused rat heart reveals a potent vasoconstrictor effect of the
      isoprostane 8-epi PGF2alpha by an action on the thromboxane receptor. 8. The data
      also suggest that, since 8-epi PGF2alpha is a partial agonist at the thromboxane
      receptor, thromboxane receptor reserve is increased by oxidative stress.

PMID- 10205004
TI  - Conformational restraints revealing bioactive beta-bend structures for halpha
      CGRP8-37 at the CGRP2 receptor of the rat prostatic vas deferens.
AB  - 1. The main aim of this study was to identify putative beta-bends and the role of
      the N- and C-terminus in the CGRP receptor antagonist halpha CGRP8-37, which was
      measured against halpha CGRP inhibition of twitch responses in the rat prostatic
      vas deferens. 2. With a bend-biasing residue (proline) at position 16 in halpha
      CGRP8-37 (10(-5) M) an inactive compound was produced, while alanine at the same
      position retained antagonist activity (apparent pKB 5.6+/-0.1 at 10(-5) M).
      Proline at position 19 within halpha CGRP8-37 (10(-5) M) was an antagonist
      (apparent pKB 5.8+/-0.1). 3. Incorporation of a bend-forcing structure (beta-turn
      dipeptide or BTD) at either positions 19,20 or 33,34 in halpha CGRP8-37 (10(-5)
      M) antagonized halpha CGRP responses (apparent pKB 6.0+/-0.1 and 6.1+/-0.1,
      respectively). Replacement by BTD at both positions 19,20 and 33,34 within halpha
      CGRP8-37 competitively antagonized responses to halpha CGRP (pA2 6.2; Schild plot
      slope 1.0+/-0.1). 4. Halpha CGRP8-37 analogues (10(-5) M), substituted at the N
      terminus by either glycine8, or des-NH2 valine8 or proline8 were all antagonists
      against halpha CGRP (apparent pKB 6.1+/-0.1, 6.5+/-0.1 and 6.1+/-0.1,
      respectively), while halpha CGRP8-37 (10(-5) M) substituted in three places by
      proline8 and glutamic acid10,14 was inactive. 5. Replacement of the C-terminus by
      alanine amide37 in halpha CGRP8-37 (10(-5) M) failed to antagonize halpha CGRP
      responses. 6. Peptidase inhibitors did not alter either the agonist potency of
      halpha CGRP or the antagonist affinities of halpha CGRP8-37 BTD19,20 and 33,34
      and halpha CGRP8-37 Gly8 (against halpha CGRP responses). 7. In conclusion, two
      beta-bends at positions 18-21 and 32-35 are compatible with high affinity by BTD
      and is the first approach of modelling the bioactive structure of halpha CGRP8
      37. Further, the N-terminus of halpha CGRP8-37 is not essential for antagonism,
      while the C-terminus interacts directly with CGRP receptor binding sites of the
      rat vas deferens.

PMID- 10205006
TI  - Adenosine 5'-triphosphate and neuropeptide Y are co-transmitters in conjunction
      with noradrenaline in the human saphenous vein.
AB  - 1. Human saphenous veins were used to assess the cooperative participation of
      adenosine 5-triphosphate (ATP), neuropeptide Y (NPY), and noradrenaline (NA) in
      the vasomotor responses elicited following electrical depolarization of the
      perivascular nerve terminals. Rings from recently dissected human biopsies were
      mounted to record isometric muscular contractions; the motor activity elicited in
      the circular muscle layer following electrical depolarization (2.5-20 Hz, 50 V,
      0.5 msec) were recorded. 2. Incubation of the biopsies with either 100 nM
      tetrodotoxin (TTX) or 1 microM guanethidine abolished the vasomotor response
      elicited by electrical nerve depolarization. The independent application of
      either ATP or NA to vein rings induced concentration-dependent contractions. 3.
      Tissue incubation with 30 microM suramin or 10 nM prazosin produced 10 fold
      rightward displacements of the alpha,beta-methylene ATP and NA concentration
      response curves respectively. NPY contracted a limited number of biopsies, the
      vasoconstriction elicited was completely blocked by 1 microM BIBP 3226. A 5 min
      incubation of the biopsies with 10-100 nM NPY synergized, in a concentration
      dependent fashion, both the ATP and the ATP analogue-induced contractions.
      Likewise, tissue preincubation with 10 nM NPY potentiated the vasomotor responses
      evoked with 20-60 nM NA. 4. Neither suramin, BIBP 3226, nor prazosin was
      individually able to significantly modify the derived frequency-tension curves.
      In contrast, the co-application of 30 microM suramin and 10 nM prazosin or 30
      microM suramin and 1 microM BIBP 3226, elicited a significant (P<0.01) downward
      displacement of the respective frequency-tension curves. 5. The simultaneous
      application of the three antagonists-30 microM suramin, 1 microM BIBP 3226 and 10
      nM prazosin-caused a significantly greater displacement of the frequency-tension
      curve than that achieved in experiments using two of these antagonists. 6.
      Electrically-evoked vasomotor activity is blocked to a larger extent by tissue
      incubation with 2.5 microM chloroethylclonidine and 30 microM suramin rather than
      with 10 nM 5 methyl urapidil and 30 microM suramin. As a result, the alpha1
      adrenoceptor involved in the vasomotor activity has tentatively been associated
      with the alpha1B adrenoceptor family subtype. 7. Results support the
      physiological role of ATP in sympathetic neurotransmission. The present results
      are consistent with the working hypothesis that human sympathetic vasomotor
      reflexes involve the coordinated motor action of ATP, NPY, and NA acting on
      vascular smooth muscle cells. The present results support the concept of
      sympathetic co-transmission in the human saphenous vein.

PMID- 10205007
TI  - Effect of protein kinase A inhibitors on the production of Abeta40 and Abeta42 by
      human cells expressing normal and Alzheimer's disease-linked mutated betaAPP and
      presenilin 1.
AB  - 1. We previously established that the formation of both alpha- and beta/gamma
      secretase-derived products generated by human embryonic kidney 293 cells (HEK293)
      expressing either wild type or mutant betaAPP could be stimulated by agonists of
      the cyclic AMP/protein kinase A pathways. This cyclic AMP-dependent effect
      modulates post-translational events since it is not prevented by actinomycin D or
      cycloheximide. 2. We show here that two protein kinase A inhibitors, H89 and PKI,
      both trigger dose-dependent inhibition of the basal constitutive production of
      Abeta40 and Abeta42 by HEK293 cells expressing wild type betaAPP751. 3. H89 also
      potently inhibits the total Abeta produced by the neocortical neuronal cell line
      TSM1. 4. These two inhibitors also drastically reduce the recovery of Abeta40 and
      Abeta42 produced by HEK293 cells expressing the Swedish (Sw) betaAPP and M146V
      presenilin 1 (PS1) mutations responsible for cases of the early-onset forms of
      Familial Alzheimer's disease (FAD). 5. By contrast, H89 and PKI do not
      significantly affect the recovery of the physiological alpha-secretase-derived
      fragment APPalpha. 6. Our study indicates that protein kinase A inhibitors
      selectively lower the formation of Abeta40 and Abeta42 in human cells expressing
      normal and mutant betaAPP and PS1 without affecting the physiological alpha
      secretase pathway in these cells. Selective inhibitors of protein kinase A may be
      of therapeutic value in both sporadic and Familial Alzheimer's disease, since
      they may decrease the production of Abeta that is thought to be responsible for
      the neurodegenerative process.

PMID- 10205008
TI  - Characterization of airway and vascular responses in murine lungs.
AB  - 1. We characterized the responses of murine airways and pulmonary vessels to a
      variety of endogenous mediators in the isolated perfused and ventilated mouse
      lung (IPL) and compared them with those in precision-cut lung slices. 2. Airways:
      The EC50 (microM) for contractions of airways in IPL/slices was methacholine
      (Mch), 6.1/1.5>serotonin, 0.7/2.0>U46619 (TP-receptor agonist),
      0.1/0.06>endothelin-1, 0.1/0.05. In the IPL, maximum increase in airway
      resistance (RL) was 0.6, 0.4, 0.8 and 11 cmH2O s ml(-1), respectively. Adenosine
      (< or =1 mM), bombesin (< or =100 microM), histamine (< or =10 mM), LTC4 (< or =1
      microM), PAF (0.25 microM) and substance P (< or =100 microM) had only weak
      effects (<5% of Mch) on RL. 3. Vessels: The EC50 (microM) for vasoconstriction in
      the IPL was LTC4, 0.06>U46619, 0.05<endothelin-1, 0.02. The maximum increase in
      pulmonary artery pressure (PAP) was 11, 41 and 48 cmH2O, respectively. At 250 nM,
      the activity of PAF was comparable to that of LTC4. At 100 microM only, substance
      P caused a largely variable increase in PAP. Serotonin, adenosine, bombesin,
      histamine and Mch had no or only very small effects on PAP. 4.
      Hyperresponsiveness: In both the IPL and slices, U46619 in subthreshold
      concentrations (10 nM) reduced the EC50 to 0.6 microM. In the IPL, U46619 raised
      the maximum airway response to Mch 5 fold and the maximum PAF-induced
      vasoconstriction 4 fold. 5. CONCLUSION: Murine precision-cut lung slices maintain
      important characteristics of the whole organ. The maximum reagibility of murine
      airways to endogenous mediators is serotonin<Mch<U46619<ET-1. The reagibility of
      the murine pulmonary vasculature is serotonin<LTC4 approximately = to
      PAF<U46619<ET-1. The airway and vessel hyperreactivity induced by U46619 raises
      the possibility that thromboxane contributes directly to airway
      hyperresponsiveness in various experimental and clinical settings.

PMID- 10205009
TI  - Limited anti-inflammatory efficacy of cyclo-oxygenase-2 inhibition in carrageenan
      airpouch inflammation.
AB  - 1. Cyclo-oxygenase-2 (COX-2) is expressed at sites of inflammation and is
      believed to be the major source of inflammation-associated prostaglandin
      synthesis. Selective inhibition of COX-2 has been suggested to produce anti
      inflammatory effects with reduced toxicity in the gastrointestinal tract. We
      examined the extent to which suppression of COX-2 led to inhibition of various
      components of inflammation in the carrageenan-airpouch model in the rat. 2.
      Indomethacin (> or =0.3 mg kg(-1)), nimesulide (> or =3 mg kg(-1)) and the
      selective COX-2 inhibitor, SC-58125 (> or =0.3 mg kg(-1)), significantly
      suppressed the production of prostaglandin E2 at the site of inflammation. At
      higher doses, indomethacin (> or =1 mg kg(-1)) and nimesulide (30 mg kg(-1)), but
      not SC-58125 (up to 10 mg kg(-1)), significantly inhibited COX-1 activity (as
      measured by whole blood thromboxane synthesis). 3. All three test drugs
      significantly reduced the volume of exudate in the airpouch, but only at doses
      greater than those required for substantial (>90%) suppression of COX-2 activity.
      Similarly, reduction of leukocyte infiltration was only observed with the doses
      of indomethacin and nimesulide that caused significant suppression of COX-1
      activity. 4. SC-58125 did not significantly affect leukocyte infiltration into
      the airpouch at any dose tested (up to 10 mg kg(-1)). A second selective COX-2
      inhibitor, Dup-697, was also found to suppress exudate PGE2 levels without
      significant effects on leukocyte infiltration. 5. These results indicate that
      selective inhibition of COX-2 results in profound suppression of PGE2 synthesis
      in the carrageenan-airpouch, but does not affect leukocyte infiltration. Exudate
      volume was only reduced with the highly selective COX-2 inhibitor when a dose far
      above that necessary for suppression of COX-2 activity was used. Inhibition of
      leukocyte infiltration was observed with indomethacin and nimesulide, but only at
      doses that inhibited both COX-1 and COX-2.

PMID- 10205010
TI  - Inhibition by simvastatin, but not pravastatin, of glucose-induced cytosolic Ca2+
      signalling and insulin secretion due to blockade of L-type Ca2+ channels in rat
      islet beta-cells.
AB  - 1. Hypercholesterolaemia often occurs in patients with type 2 diabetes, who
      therefore encounter administration of HMG-CoA reductase inhibitors. Alteration of
      pancreatic beta-cell function leading to an impaired insulin secretory response
      to glucose plays a crucial role in the pathogenesis of type 2 diabetes.
      Therefore, it is important to examine the effects of HMG-CoA reductase inhibitors
      on beta-cell function. 2. Cytosolic Ca2+ concentration ([Ca2+]i) plays a central
      role in the regulation of beta-cell function. The present study examined the
      effects of HMG-CoA reductase inhibitors on the glucose-induced [Ca2+]i signalling
      and insulin secretion in rat islet beta-cells. 3. Simvastatin, a lipophilic HMG
      CoA reductase inhibitor, at 0.1-3 microg ml(-1) concentration-dependently
      inhibited the first phase increase and oscillation of [Ca2+]i induced by 8.3 mM
      glucose in single beta-cells. The less lipophilic inhibitor, simvastatin-acid,
      inhibited the first phase [Ca2+]i increase but was two orders of magnitude less
      potent. The hydrophilic inhibitor, pravastatin (100 microg ml(-1), was without
      effect on [Ca2+]i. 4. Simvastatin (0.3 microg ml(-1)), more potently than
      simvastatin-acid (30 microg ml(-1)), inhibited glucose-induced insulin secretion
      from islets, whereas pravastatin (100 microg ml(-1)) had no effect. 5. Whole-cell
      patch clamp recordings demonstrated a reversible inhibition of the beta-cell L
      type Ca2+ channels by simvastatin, but not by pravastatin. Simvastatin also
      inhibited the [Ca2+]i increases by L-arginine and KCl, agents that act via
      opening of L-type Ca2+ channels. 6. In conclusion, lipophilic HMG-CoA reductase
      inhibitors can inhibit glucose-induced [Ca2+]i signalling and insulin secretion
      by blocking L-type Ca2+ channels in beta-cells, and their inhibitory potencies
      parallel their lipophilicities. Precaution should be paid to these findings when
      HMG-CoA reductase inhibitors are used clinically, particularly in patients with
      type 2 diabetes.

PMID- 10205011
TI  - Role of potassium channels in the antinociception induced by agonists of alpha2
      adrenoceptors.
AB  - 1. The effect of the administration of pertussis toxin (PTX) as well as
      modulators of different subtypes of K+ channels on the antinociception induced by
      clonidine and guanabenz was evaluated in the mouse hot plate test. 2.
      Pretreatment with pertussis toxin (0.25 microg per mouse i.c.v.) 7 days before
      the hot-plate test, prevented the antinociception induced by both clonidine (0.08
      0.2 mg kg(-1), s.c.) and guanabenz (0.1-0.5 mg kg(-1), s.c.). 3. The
      administration of the K(ATP) channel openers minoxidil (10 microg per mouse,
      i.c.v.), pinacidil (25 microg per mouse, i.c.v.) and diazoxide (100 mg kg(-1),
      p.o.) potentiated the antinociception produced by clonidine and guanabenz whereas
      the K(ATP) channel blocker gliquidone (6 microg per mouse, i.c.v.) prevented the
      alpha2 adrenoceptor agonist-induced analgesia. 4. Pretreatment with an antisense
      oligonucleotide (aODN) to mKv1.1, a voltage-gated K+ channel, at the dose of 2.0
      nmol per single i.c.v. injection, prevented the antinociception induced by both
      clonidine and guanabenz in comparison with degenerate oligonucleotide (dODN)
      treated mice. 5. The administration of the Ca2+-gated K+ channel blocker apamin
      (0.5-2.0 ng per mouse, i.c.v.) never modified clonidine and guanabenz analgesia.
      6. At the highest effective doses, none of the drugs used modified animals' gross
      behaviour nor impaired motor coordination, as revealed by the rota-rod test. 7.
      The present data demonstrate that both K(ATP) and mKv1.1 K+ channels represent an
      important step in the transduction mechanism underlying central antinociception
      induced by activation of alpha2 adrenoceptors.

PMID- 10205012
TI  - Activation of adenylate cyclase by human recombinant sst5 receptors expressed in
      CHO-K1 cells and involvement of Galphas proteins.
AB  - 1. The coupling of the human somatostatin sst5 receptor recombinantly expressed
      in Chinese hamster ovary (CHO-K1) cells to adenylate cyclase was investigated
      using receptor selective ligands. 2. Forskolin (10 microM)-stimulated adenosine
      3': 5'-cyclic monophosphate (cyclic AMP) accumulation was inhibited by
      somatostatin-14 and a number of receptor-selective agonists with a rank order of
      agonist potency typical of the sst5 receptor. L-362,855 and BIM-23056 behaved as
      full agonists. At higher somatostatin-14 concentrations there was sub-maximal
      inhibition resulting in a bell-shaped concentration-effect relationship.
      Pertussis toxin (PTx; 100 ng ml(-1), 18 h) pre-treatment abolished agonist
      mediated inhibition of cyclic AMP accumulation and markedly enhanced stimulation
      of cyclic AMP at higher agonist concentrations. 3. The concentration of
      prostaglandin E2 (PGE2) in the incubation media was raised 14 fold by 1 microM
      somatostatin-14 but was insufficient to stimulate adenylate cyclase activity via
      endogenous prostanoid receptors. 4. Pre-treatment with cholera toxin (ChTx; 20
      microg ml(-1), 18 h) markedly inhibited sst5 receptor-mediated increases in
      cyclic AMP formation in intact cells. Somatostatin-14-stimulated cyclic AMP
      accumulation was also observed in sst5 receptor containing CHO-K1 membranes and
      was inhibited by the synthetic peptide Galphasacetyl-354-372-amide (100 microM)
      by 65.9+/-3.5%, implicating a Galphas protein involvement in this response. 5.
      Activation of Galphas proteins by somatostatin-14 could be demonstrated with
      [35S]-guanosine 5'-[gamma-thio]triphosphate ([35S]-GTPgammaS) binding and
      subsequent immunoprecipitation of 35S labelled Galphas proteins with anti-Galphas
      serum. 6. These data show that the sst5 receptor is very efficiently coupled in a
      negative manner to adenylate cyclase. However, at higher agonist concentrations
      the receptor can also mediate activation of adenylate cyclase by a mechanism
      apparently involving Galphas protein activation.

PMID- 10205013
TI  - Actions of 3-[2-phosphonomethyl[1,1-biphenyl]-3-yl]alanine (PMBA) on cloned
      glycine receptors.
AB  - 1. PMBA is a novel antagonist of strychnine-sensitive glycine receptors in the
      rat spinal cord, however, its mode of action is unknown. The actions of PMBA on
      rat glycine receptor alpha1 and alpha2 homomers in Xenopus oocytes were studied
      under two-electrode voltage-clamp. 2. Co-application of PMBA and glycine to both
      alpha1 and alpha2 homomers yielded inward currents which decayed to a steady
      state. Responses rose slowly to the same steady-state amplitude following a 2 min
      pre-incubation in PMBA. Strychnine, but not picrotoxinin, showed similar
      antagonism to PMBA. The potency of PMBA was independent of membrane potential
      between -100 and 0 mV. 3. When tested against EC50 concentrations of glycine,
      PMBA was almost equally potent on alpha1 (IC50, 406+/-41 nM: Hill coefficient,
      1.5+/-0.2) and alpha2 (IC50, 539+/-56 nM; Hill coefficient, 1.4+/-0.2) homomers.
      4. PMBA (1-I0 microM) and strychnine (200 nM) reduced the potency of glycine and
      the amplitude of the maximal agonist response of alpha1 and alpha2 homomers. In
      10 microM PMBA, two distinct classes of glycine response were observed on alpha2,
      only a single class of responses were observed on alpha1. 5. There are
      similarities in PMBA and strychnine antagonism, although these compounds are
      structurally distinct. The possibility that PMBA interacts at two binding sites
      which differ in alpha1 and alpha2 subunits is discussed. PMBA may provide a lead
      structure for novel antagonists with which to investigate structural differences
      in glycine receptor at alpha1 and alpha2 subunits.

PMID- 10205014
TI  - The putative melatonin receptor antagonist GR128107 is a partial agonist on
      Xenopus laevis melanophores.
AB  - 1. GR128107 (3-(1-acetyl-3-methyl-piperidine)-5-methoxyindole) has previously
      been reported to be a competitive melatonin receptor antagonist in blocking
      melatonin inhibition of [3H]-dopamine release from rabbit retina, a response
      mediated by the MT2 receptor subtype. 2. GR128107, like melatonin, induced a
      rapid (maximum response in 60-90 min) pigment aggregation in a clonal line of
      Xenopus laevis melanophores. GR128107 behaved as a partial agonist (pEC50 8.58+/
      0.03, n=3) with an Emax of 0.83 (relative to melatonin, pEC50 10.09+/-0.03, n=3).
      3. The concentration-response curve for pigment granule aggregation to both
      melatonin and GR128107 was displaced in a parallel, rightward manner by melatonin
      receptor antagonists with very similar potencies; estimated pKB RJ252 (against
      melatonin 4.60/against GR128107 4.54) < GR135533 (6.40/6.14) < Luzindole
      (6.45/6.49) < S20929 (6.58/6.65) < 4-P-PDOT (6.73/6.85). 4. Both melatonin- and
      GR128107-induced pigment granule aggregation was prevented by pretreatment of
      melanophores with pertussis toxin (10-1000 ng ml(-1)). 5. Prolonged pre-treatment
      of melanophores with melatonin desensitized the pigment aggregation response to
      GR128107. In desensitized cells, the maximal aggregation produced by GR128107 was
      only 0.27+/-0.01 (n=4) and the pEC50 was reduced (vehicle 8.57+/-0.12; melatonin
      pre-treated 7.84+/-0.09, n=4). The maximal response to melatonin in desensitized
      melanophores was unchanged but the pEC50 was reduced (vehicle 10.49+/-0.03;
      melatonin pre-treated 9.83+/-0.04, n=4). 6. These results demonstrate that
      GR128107 induces pigment granule aggregation in Xenopus melanophores by
      activating a cell membrane melatonin receptor coupled via a pertussis toxin
      sensitive G-protein. 7. The partial agonist activity of GR128107 in melanophores
      may be apparent because of the very high density of melatonin receptors in these
      cells (Bmax 1223 fmol mg protein(-1)) compared to the low density of sites in
      rabbit retina (Bmax 3.1 fmol mg protein(-1)). This suggestion is supported by the
      finding that GR128107, like melatonin, acted as a full agonist and inhibited
      forskolin-stimulation of cyclic AMP accumulation in NIH-3T3 cells expressing a
      high density of human mt1 or MT2 receptors.

PMID- 10205015
TI  - Inverse agonist activity of pirenzepine at M2 muscarinic acetylcholine receptors.
AB  - 1. The intrinsic properties of muscarinic ligands were studied through their
      binding properties and their abilities to modulate the GTPase activity of G
      proteins coupled to muscarinic M2 receptors in pig atrial sarcolemma. 2.
      Competition binding experiments were performed with [3H]-oxotremorine-M to assess
      the affinity of receptors coupled to G proteins (R*), with [3H]-N
      methylscopolamine ([3H]-NMS) to estimate the affinities of coupled and uncoupled
      receptors (R*+R) and with [3H]-NMS in the presence of GppNHp to assess the
      affinity of uncoupled receptors (R). 3. The ranking of Ki values for the agonist
      carbachol was R*<<R*+R<<R (0.95, 124 and 1017 nM). Ki values for atropine and AF
      DX 116 were similar for the three binding conditions (0.34, 0.42, 0.41 and 19,
      22, 32 nM). The ranking of Ki values for pirenzepine was R*>R*+R>R (174, 155, 115
      nM), suggesting inverse agonism. 4. The Vmax of the basal high affinity GTPase
      activity of pig atrial sarcolemma was increased by mastoparan and decreased by
      GPAnt-2 indicating the relevance of this activity to G proteins coupled to
      receptors (R*). The K(M) value (0.26-0.33 microM) was not modified by mastoparan
      or GPAnt-2. 5. Carbachol increased the Vmax of GTP hydrolysis (EC50 8.1+/-0.3
      microM), whereas atropine and AF-DX 116, up to 1 mM, did not modify it.
      Pirenzepine decreased the Vmax of GTP hydrolysis (EC50 77.5+/-10.3 microM). This
      effect was enhanced when KCI was substituted for NaCl (EC50 11.0+/-0.8 microM)
      and was antagonized by atropine and AF-DX 116 (IC50 0.91+/-0.71 and 197+/-85 nM).
      6. Pirenzepine is proposed as an inverse agonist and atropine and AF-DX 116 as
      neutral antagonists at the muscarinic M2 receptor.

PMID- 10205016
TI  - Effects of short chain alkanols on the inducible nitric oxide synthase in a glial
      cell line.
AB  - 1. Ethanol inhibits inducible nitric oxide synthase (iNOS) expression in C6
      glioma cells by an unknown mechanism. Because relatively high concentrations are
      needed for inhibition in drug-naive cells (IC50 approximately = to 150 mM),
      suppression due to cytotoxicity is one possible mechanism that has not been ruled
      out. Therefore, the present study examined the effects of ethanol and other
      alkanols on C6 glioma cell viability and iNOS activity to better understand the
      mechanism for inhibition. 2. iNOS expression was induced in cell culture with
      lipopolysaccharide and phorbol ester treatment. Nitrite accumulation in culture
      medium, the in vitro conversion of [3H]-L-arginine to [3H]-L-citrulline, and
      immunoblotting were used to quantify iNOS induction and activity. Trypan blue
      exclusion, extracellular release of lactate dehydrogenase, and quantity of total
      cell protein were used as measures of viability. 3. Short chain alkanols,
      methanol through 1-heptanol, concentration-dependently inhibited nitrite
      accumulation. Longer chain alkanols, 1-octanol and 1-decanol, did not except at
      cytotoxic concentrations. Experiments indicated short chain alkanol inhibition
      was not due to direct actions on iNOS catalytic activity, but that it transpires
      during iNOS induction. Immunoblots showed reduced iNOS protein levels. 4.
      Correlation analysis ruled out iNOS inhibition as being due to decreased cell
      number, total cell protein, or cell viability. In contrast, there was significant
      correlation with physical measures of lipophilicity. 5. In conclusion, inhibition
      of iNOS expression by ethanol and other short chain alkanols is not due to
      cytotoxicity. Instead, the strong correlation with lipophilicity suggests the
      inhibition derives from an interaction with unknown hydrophobic cellular sites.

PMID- 10205017
TI  - Pro- and anti-inflammatory actions of thrombin: a distinct role for proteinase
      activated receptor-1 (PAR1).
AB  - 1. Thrombin has well characterized pro-inflammatory actions that have recently
      been suggested to occur via activation of its receptor, proteinase-activated
      receptor-1 (PAR1). 2. In the present study, we have compared the effects of
      thrombin to those of two peptides that selectively activate the PAR1 receptor, in
      a rat hindpaw oedema model. We have also examined whether or not thrombin can
      exert anti-inflammatory activity in this model. 3. Both thrombin and the two PAR1
      activating peptides induced significant oedema in the rat hindpaw following
      subplantar injection. 4. The oedema induced by thrombin was abolished by pre
      incubation with hirudin, and was markedly reduced in rats in which mast cells
      were depleted through treatment with compound 48/80 and in rats pretreated with
      indomethacin. In contrast, administration of the PAR1 activating peptides
      produced an oedema response that was not reduced by indomethacin and was only
      slightly reduced in rats pretreated with compound 48/80. 5. Co-administration of
      thrombin together with a PAR1 activating receptor resulted in a significantly
      smaller oedema response than that seen with the PAR1 activating peptide alone.
      This anti-inflammatory effect of thrombin was abolished by pre-incubation with
      hirudin. 6. These results demonstrate that the pro-inflammatory effects of
      thrombin occur through a mast-cell dependent mechanism that is, at least in part,
      independent of activation of the PAR1 receptor. Moreover, thrombin is able to
      exert anti-inflammatory effects that are also unrelated to the activation of
      PAR1.

PMID- 10205019
TI  - Characterization of receptors for calcitonin gene-related peptide and
      adrenomedullin on the guinea-pig vas deferens.
AB  - 1. The receptors which mediate the effects of calcitonin gene-related peptide
      (CGRP), amylin and adrenomedullin on the guinea-pig vas deferens have been
      investigated. 2. All three peptides cause concentration dependant inhibitions of
      the electrically stimulated twitch response (pD2s for CGRP, amylin and
      adrenomedullin of 7.90+/-0.11, 7.70+/-0.19 and 7.25+/-0.10 respectively). 3.
      CGRP8-37 (1 microM) and AC187 (10 microM) showed little antagonist activity
      against adrenomedullin. 4. Adrenomedullin22-52 by itself inhibited the
      electrically stimulated contractions of the vas deferens and also antagonized the
      responses to CGRP, amylin and adrenomedullin. 5. [125I]-adrenomedullin labelled a
      single population of binding sites in vas deferens membranes with a pIC50 of 8.91
      and a capacity of 643 fmol mg(-1). Its selectivity profile was adrenomedullin>
      AC187>CGRP=amylin. It was clearly distinct from a site labelled by [125I]-CGRP
      (pIC50=8.73, capacity=114 fmol mg(-1), selectivity
      CGRP>amylin=AC187>adrenomedullin). [125I]-amylin bound to two sites with a total
      capacity of 882 fmol mg(-1). 6. Although CGRP has been shown to act at a CGRP2
      receptor on the vas deferens with low sensitivity to CGRP8-37, this antagonist
      displaced [125I]-CGRP with high affinity from vas deferens membranes. This
      affinity was unaltered by increasing the temperature from 4 degrees C to 25
      degrees C, suggesting the anomalous behaviour of CGRP8-37 is not due to
      temperature differences between binding and functional assays.

PMID- 10205020
TI  - Immunochemical localization of calretinin in the retina of the turbot (Psetta
      maxima) during development.
AB  - The expression of the calcium-binding protein calretinin was analysed by
      immunohistochemistry techniques in the retina of turbot (Psetta maxima) from
      embryonic to juvenile stages. Calretinin immunoreactivity was first detected in
      retinae from newly hatched larvae, in which the anlage of the inner plexiform
      layer and a subset of amacrine and ganglion cells displayed a faint
      immunolabelling. First appearance of photoreceptors during larval life coincided
      with an increase in the intensity of the labelling. During subsequent larval
      development, the expression of calretinin affected distinctive retinal
      components. The inner plexiform layer, optic fiber layer, and a population of
      amacrine and ganglion cells were invariably labelled. Occasional bipolar cells
      were labelled at the end of the larval period. By metamorphosis, calretinin is
      sequentially expressed in horizontal cells, and bipolar immunoreactive cells
      become numerous. The pattern of calretinin immunoreactivity of the inner
      plexiform layer changes from the larval to juvenile period. In all cases,
      calretinin immunoreactivity exhibited variations between the peripheral retina,
      which contains the most recently differentiated retinal components, and the
      remainder of the differentiated retina. Our results suggest that the progressive
      expression of calretinin in the turbot retina appears associated with some degree
      of neuronal differentiation. Once the definitive pattern of calretinin
      immunoreactivity is established in the turbot retina, both similarities and
      differences with the calretinin location in the retina of other vertebrates can
      be demonstrated.

PMID- 10205018
TI  - Characterization and tissue location of the neural adenosine receptor in the rat
      ileum.
AB  - 1. The aim of the present investigation was to characterize and determine the
      tissue location of the adenosine receptors present in the rat ileum using a
      method that detects drug action on the cholinergic nerves innervating the
      longitudinal and circular muscles. 2. The non-selective adenosine agonist, NECA
      (10 and 100 nM) caused significant concentration-related reductions in the
      circular muscle responses to transmural stimulation over the frequency range of
      2.5-40 Hz, but did not affect the responses of the longitudinal muscle, nor did
      it reduce the muscle responses of the guinea-pig ileum. 3. The affinity order of
      antagonists at inhibiting the effect of NECA on the circular muscle was: CPDPX>8
      PT>DMPX with apparent pA2 values of 9.31, 7.54 and 5.63 respectively. CPDPX (10
      100 nM) caused parallel displacements of the concentration-effect curves to CPA
      with a pKb value of 9.15 and Schild slope of 1.03. 4. The agonists previously
      tested in the rat jejunum peristaltic reflex preparation were also shown to
      inhibit responses of the rat ileum in the following decreasing order of potency:
      CPA>NECA>2-CADO>R-PIA>S-PIA>>PAA. In addition, CHA and CCPA were also potent
      agonists. NECA (100 nM) and CPA (32 nM) did not inhibit carbachol (1 microM)
      induced tone of tissues pre-treated with TTX (1 microM). 5. In conclusion, the
      rat ileum contains inhibitory A1 adenosine receptors situated on cholinergic
      nerve endings innervating the circular muscle.

PMID- 10205021
TI  - Severe neuronal losses with age in the parietal cortex and ventrobasal thalamus
      of mice transgenic for the human NF-L neurofilament protein.
AB  - Transgenic mice expressing human light neurofilament protein (NF-L) display early
      perikaryal accumulations of disarrayed neurofilaments in layers II/III of the
      parietal cortex and in the ventrobasal complex of thalamus. This cytoskeletal
      abnormality, reflected by strong NF-L immunoreactivity, is transient in the
      developing cortex but persists until old age in the thalamus. To investigate
      whether it leads to neuronal death, the unbiased cell counting method of the
      dissector was applied to the parietal cortex and the thalamus of normal and
      transgenic mice at various postnatal (P10, P20, P90) and advanced ages (14-18
      months). Similar data were also obtained from the primary visual cortex free of
      NF-L accumulation. Compared with normal, the total number of neurons in the
      parietal (but not occipital) cortex of transgenic mice showed little change
      during the postnatal period, but decreased markedly with old age, particularly in
      layers II/III. Severe neuronal loss was also documented in the thalamic
      ventrobasal complex of aged transgenic mice. The delayed neuronal death in the
      parietal cortex, occurring long after recovery from the NF-L accumulations, was
      suggestive of a combination of deleterious factors, including the early
      overproduction of neurofilament protein and subsequent loss of afferent input
      from the affected somatosensory thalamic nuclei. Furthermore, strong accumulation
      of lipofuscin in the neurons of aged transgenic mice suggested that oxidative
      stress partakes in the mechanisms through which NF-L overproduction compromises
      neuronal viability.

PMID- 10205022
TI  - Adult-generated neurons in the dentate gyrus send axonal projections to field CA3
      and are surrounded by synaptic vesicles.
AB  - The subgranule zone of the dentate gyrus in rats has been shown to be
      proliferative into adulthood and senescence. However, the connectivity of newly
      generated, identified neurons in the adult has not been definitively described.
      In the present study, 9 weeks after a series of intraperitoneal injections of 5
      bromo-2'-deoxyuridine (BrdU), animals received stereotaxic iontophoretic
      injections of Fluoro-Gold (FG) into field CA3. Three weeks after FG injections,
      sections were analyzed for BrdU immunoreactivity (proliferative label), FG
      retrograde label, and either calbindin-D28k or synaptophysin
      immunohistochemistry. A large proportion (up to 44%) of BrdU-labeled cells in the
      dentate gyrus within regions of FG retrograde label incorporated FG. All of the
      doubly labeled (BrdU-FG) neurons also immunolabeled with the antibody to
      calbindin-D28k. Many doubly labeled (BrdU-FG) cells were also surrounded in three
      planes by synaptophysin immunoreactivity. We conclude that newly generated
      neurons in the dentate gyrus have the correct immunohistochemical profile, send
      appropriate axonal projections to field CA3, and are surrounded by profiles
      containing synaptic vesicle proteins.

PMID- 10205023
TI  - Regeneration of the enteric nervous system in the sea cucumber Holothuria
      glaberrima.
AB  - Among higher metazoans, echinoderms exhibit the most impressive capacity for
      regeneration. Holothurians, or sea cucumbers, respond to adverse stimuli by
      autotomizing and ejecting their visceral organs, which are then regenerated.
      Neuronal fibers and cell bodies are present within the viscera, but previous
      regeneration studies have not accounted for the nervous component. We used light
      microscopic immunocytochemistry and ultrastructural studies to describe the
      regeneration of the enteric nervous system in the sea cucumber Holothuria
      glaberrima. This study provides evidence that the enteric nervous system of this
      echinoderm regenerates after evisceration and that in 3-5 weeks the regenerated
      system is virtually identical to that of noneviscerated animals. The regeneration
      of the enteric nervous system occurs parallel to the regeneration of other organ
      components. Nerve fibers and cells are observed within the mesenterial
      thickenings that give rise to the new intestine and within the internal
      connective tissue prior to lumen formation. We also used bromodeoxyuridine
      incorporation to show that proliferation of the neuronal population occurs in the
      regenerating intestine. The regeneration of the nervous system commands high
      interest because members of the closely related phylum Chordata either lack or
      have a very limited capacity to regenerate their nervous system. Thus,
      holothurians provide a model system to study enteric nervous system regeneration
      in deuterostomes.

PMID- 10205024
TI  - Axonal regeneration in the central nervous system of aplysia californica
      determined by anterograde transport of biocytin.
AB  - Rhythmic biting, a component of consummatory feeding behavior in the sea hare
      Aplysia californica, is eliminated following bilateral cerebral-buccal connective
      (CBC) crushes and recovers within 14 days postlesion. To assess axonal
      regeneration after CBC lesions, we used biocytin backfills of CBCs followed by
      fluorescence labeling with streptavidin-lissamine rhodamine. Anterograde
      transport of biocytin showed up to 1 mm of outgrowth by regenerating axons at 3
      days postlesion. At 7 days postlesion, the regenerated axons approached or had
      entered the ipsilateral buccal neuropil and exhibited numerous varicosities; the
      average rate of axonal growth was 326 microm/day for the longest, most rapidly
      growing axons labeled in the CBC. The number of varicosities on labeled axons,
      suggestive of intercellular interactions, was increased dramatically at all times
      postlesion. At 14 and 20 days postlesion, regenerated axons branched extensively
      in the ipsilateral buccal neuropil, entered the contralateral buccal neuropil,
      and entered peripheral nerves on both sides of the midline. At these later times
      postlesion, some labeled axons encircled unlabeled buccal cell bodies and
      exhibited branches containing numerous varicosities, indicative of axosomatic
      contacts. Some regenerating axons were observed in the sheath of the CBC, but the
      vast majority of labeled axons remained confined to the connective core, as in
      control preparations. The bilateral projections within the buccal ganglia of
      labeled cerebral-to-buccal axons and the large number of varicosities present on
      these processes are indicative of regenerating axons and synapses that likely
      contribute to the functional recovery of rhythmic biting.

PMID- 10205025
TI  - Cortical connections of the dorsomedial visual area in old world macaque monkeys.
AB  - The connections of a wedge of densely myelinated cortex along the dorsomedial
      border of V2 were determined by injecting tracers into this region in macaque
      monkeys. According to previous descriptions, this cortex would constitute parts
      of dorsal V3 and V3A, or a dorsomedial visual area, DM, homologous to the DM
      described in prosimians and New World monkeys. Injections of wheat germ
      agglutinin conjugated to horseradish peroxidase or various fluorescent tracers
      demonstrated connections with architectonically defined V1, V2, and the middle
      temporal area, as well as regions of visual areas known as the ventral posterior
      parietal area, the rostral dorsolateral area or rostral V4, ventral posterior
      cortex and more rostral cortex in the ventral temporal lobe, and medial and
      dorsointermediate areas. Other sparser and less consistently revealed connections
      were with the medial superior temporal area, the area of the fundus of the
      superior temporal sulcus, and the caudal dorsolateral area. Distributions of
      labeled cells in V1 varied in relationship to the pattern of cytochrome oxidase
      blobs and interblobs in a manner suggesting a heterogeneous pattern of
      terminations from blob and interblob regions within DM. Major similarities in
      overall connections of the DM region in macaques with DM connections described in
      New World monkeys and prosimian galagos support the conclusion that the same
      visual area, DM, has been identified in all these primates.

PMID- 10205026
TI  - Localization of orphanin FQ (nociceptin) peptide and messenger RNA in the central
      nervous system of the rat.
AB  - Orphanin FQ (OFQ) is the endogenous agonist of the opioid receptor-like receptor
      (ORL-1). It and its precursor, prepro-OFQ, exhibit structural features suggestive
      of the opioid peptides. A cDNA encoding the OFQ precursor sequence in the rat
      recently has been cloned, and the authors recently generated a polyclonal
      antibody directed against the OFQ peptide. In the present study, the authors used
      in situ hybridization and immunohistochemistry to examine the distribution of OFQ
      peptide and mRNA in the central nervous system of the adult rat. OFQ
      immunoreactivity and prepro-OFQ mRNA expression correlated virtually in all brain
      areas studied. In the forebrain, OFQ peptide and mRNA were prominent in the
      neocortex endopiriform nucleus, claustrum, lateral septum, ventral forebrain,
      hypothalamus, mammillary bodies, central and medial nuclei of the amygdala,
      hippocampal formation, paratenial and reticular nuclei of the thalamus, medial
      habenula, and zona incerta. No OFQ was observed in the pineal or pituitary
      glands. In the brainstem, OFQ was prominent in the ventral tegmental area,
      substantia nigra, nucleus of the posterior commissure, central gray, nucleus of
      Darkschewitsch, peripeduncular nucleus, interpeduncular nucleus, tegmental
      nuclei, locus coeruleus, raphe complex, lateral parabrachial nucleus, inferior
      olivary complex, vestibular nuclear complex, prepositus hypoglossus, solitary
      nucleus, nucleus ambiguous, caudal spinal trigeminal nucleus, and reticular
      formation. In the spinal cord, OFQ was observed throughout the dorsal and ventral
      horns. The wide distribution of this peptide provides support for its role in a
      multitude of functions, including not only nociception but also motor and balance
      control, special sensory processing, and various autonomic and physiologic
      processes.

PMID- 10205027
TI  - Activity-dependent refinement in the goldfish retinotectal system is mediated by
      the dynamic regulation of processes withdrawal: an in vivo imaging study.
AB  - Imaging of regenerating optic fibers in living adult goldfish was used to
      visualize arbor restructuring during activity-dependent refinement. A small
      number of neighboring retinal ganglion cells were labeled with DiI and observed
      in the tectum of the living animal for 5-7 hours during the period of activity
      dependent refinement. In contrast to earlier stages of regeneration, many optic
      arbors were surprisingly stable, showing little or no change. The observed
      changes were mainly retractions, and these were affected by retinotopic position
      and activity. Axon branches in retinotopic positions changed by much smaller
      amounts than ectopic axons, but in fish with retinal tetrodotoxin impulse
      blockade, no systematic difference was observed as a function of tectal position.
      Otherwise, impulse blockade had no notable effects.

PMID- 10205029
TI  - No centriole, no centrosome.

PMID- 10205028
TI  - How much molecular medicine do medical students need to learn?

PMID- 10205030
TI  - Apoptosis and spindle-assembly united.

PMID- 10205031
TI  - Clearing the air on an Aurora/Ipl2 family member.

PMID- 10205032
TI  - Special-interest subgroups at the ASCB: gamma-Tubulin: questions outstanding.
AB  - The annual meeting of the American Society for Cell Biology (ASCB) is a large and
      diverse gathering. At last year's meeting**The American Society for Cell Biology
      38th Annual Meeting, San Francisco, USA; 12-16 December, 1998. Program chair:
      Jennifer Lippincott-Schwartz., there were over 8000 attendees, and the topics
      discussed covered many areas of cell biology. It would be impossible to cover the
      entire meeting within a trends in CELL BIOLOGY report, so instead we are focusing
      on an aspect of it that provided some of the most interesting and fruitful
      discussions. On Saturday afternoon, before the main symposia began, there were 11
      special-interest subgroup meetings. The atmosphere at these meetings was
      informal, and they encouraged open and frank discussion of data and issues. This
      report provides a brief summary of the discussions at seven of the special
      interest subgroup meetings.

PMID- 10205033
TI  - Special-interest subgroups at the ASCB: Are there multiple roles for the Ran
      GTPase?
AB  - The annual meeting of the American Society for Cell Biology (ASCB) is a large and
      diverse gathering. At last year's meeting**The American Society for Cell Biology
      38th Annual Meeting, San Francisco, USA; 12-16 December, 1998. Program chair:
      Jennifer Lippincott-Schwartz., there were over 8000 attendees, and the topics
      discussed covered many areas of cell biology. It would be impossible to cover the
      entire meeting within a trends in CELL BIOLOGY report, so instead we are focusing
      on an aspect of it that provided some of the most interesting and fruitful
      discussions. On Saturday afternoon, before the main symposia began, there were 11
      special-interest subgroup meetings. The atmosphere at these meetings was
      informal, and they encouraged open and frank discussion of data and issues. This
      report provides a brief summary of the discussions at seven of the special
      interest subgroup meetings.

PMID- 10205034
TI  - Special-interest subgroups at the ASCB: Gap junctions.
AB  - The annual meeting of the American Society for Cell Biology (ASCB) is a large and
      diverse gathering. At last year's meeting**The American Society for Cell Biology
      38th Annual Meeting, San Francisco, USA; 12-16 December, 1998. Program chair:
      Jennifer Lippincott-Schwartz., there were over 8000 attendees, and the topics
      discussed covered many areas of cell biology. It would be impossible to cover the
      entire meeting within a trends in CELL BIOLOGY report, so instead we are focusing
      on an aspect of it that provided some of the most interesting and fruitful
      discussions. On Saturday afternoon, before the main symposia began, there were 11
      special-interest subgroup meetings. The atmosphere at these meetings was
      informal, and they encouraged open and frank discussion of data and issues. This
      report provides a brief summary of the discussions at seven of the special
      interest subgroup meetings.

PMID- 10205035
TI  - Special-interest subgroups at the ASCB: Proteoglycans and cell adhesion.
AB  - The annual meeting of the American Society for Cell Biology (ASCB) is a large and
      diverse gathering. At last year's meeting**The American Society for Cell Biology
      38th Annual Meeting, San Francisco, USA; 12-16 December, 1998. Program chair:
      Jennifer Lippincott-Schwartz., there were over 8000 attendees, and the topics
      discussed covered many areas of cell biology. It would be impossible to cover the
      entire meeting within a trends in CELL BIOLOGY report, so instead we are focusing
      on an aspect of it that provided some of the most interesting and fruitful
      discussions. On Saturday afternoon, before the main symposia began, there were 11
      special-interest subgroup meetings. The atmosphere at these meetings was
      informal, and they encouraged open and frank discussion of data and issues. This
      report provides a brief summary of the discussions at seven of the special
      interest subgroup meetings.

PMID- 10205036
TI  - Rafts ready for turning on T cells 

PMID- 10205037
TI  - Gamma tubulin and the origin of two-ness 

PMID- 10205038
TI  - Aggresomes - a novel way to die slowly 

PMID- 10205039
TI  - Getting in is easy, but how to get out? 

PMID- 10205040
TI  - Sinister depictions of DNA.

PMID- 10205041
TI  - Baroque imprints.

PMID- 10205042
TI  - Lofty insulation.

PMID- 10205043
TI  - Whatever turns you on?

PMID- 10205044
TI  - Pathogenic paradox?

PMID- 10205045
TI  - Foreign travel.

PMID- 10205046
TI  - Increased X-inactivation skewing in SLE?

PMID- 10205048
TI  - Viscosity near Earth's solid inner core 
AB  - Anomalous splitting of the two equatorial translational modes of oscillation of
      Earth's solid inner core is used to estimate the effective viscosity just outside
      its boundary. Superconducting gravimeter observations give periods of 3.5822 +/-
      0.0012 (retrograde) and 4.0150 +/- 0.0010 (prograde) hours. With the use of Ekman
      layer theory to estimate viscous drag forces, an inferred single viscosity of
      1.22 x 10(11) Pascal seconds gives calculated periods of 3.5839 and 4.0167 hours
      for the two modes, close to the observed values. The large effective viscosity is
      consistent with a fluid, solid-liquid mixture surrounding the inner core
      associated with the "compositional convection" that drives Earth's geodynamo.

PMID- 10205047
TI  - Structure of the VHL-ElonginC-ElonginB complex: implications for VHL tumor
      suppressor function.
AB  - Mutation of the VHL tumor suppressor is associated with the inherited von Hippel
      Lindau (VHL) cancer syndrome and the majority of kidney cancers. VHL binds the
      ElonginC-ElonginB complex and regulates levels of hypoxia-inducible proteins. The
      structure of the ternary complex at 2.7 angstrom resolution shows two interfaces,
      one between VHL and ElonginC and another between ElonginC and ElonginB.
      Tumorigenic mutations frequently occur in a 35-residue domain of VHL responsible
      for ElonginC binding. A mutational patch on a separate domain of VHL indicates a
      second macromolecular binding site. The structure extends the similarities to the
      SCF (Skp1-Cul1-F-box protein) complex that targets proteins for degradation,
      supporting the hypothesis that VHL may function in an analogous pathway.

PMID- 10205049
TI  - Global warming and marine carbon cycle feedbacks on future atmospheric CO2 
AB  - A low-order physical-biogeochemical climate model was used to project atmospheric
      carbon dioxide and global warming for scenarios developed by the
      Intergovernmental Panel on Climate Change. The North Atlantic thermohaline
      circulation weakens in all global warming simulations and collapses at high
      levels of carbon dioxide. Projected changes in the marine carbon cycle have a
      modest impact on atmospheric carbon dioxide. Compared with the control,
      atmospheric carbon dioxide increased by 4 percent at year 2100 and 20 percent at
      year 2500. The reduction in ocean carbon uptake can be mainly explained by sea
      surface warming. The projected changes of the marine biological cycle compensate
      the reduction in downward mixing of anthropogenic carbon, except when the North
      Atlantic thermohaline circulation collapses.

PMID- 10205050
TI  - Propagation of a magnetic domain wall in a submicrometer magnetic wire 
AB  - The motion of a magnetic domain wall in a submicrometer magnetic wire was
      detected by use of the giant magnetoresistance effect. Magnetization reversal in
      a submicrometer magnetic wire takes place by the propagation of a magnetic domain
      wall, which can be treated as a "particle." The propagation velocity of the
      magnetic domain wall was determined as a function of the applied magnetic field.

PMID- 10205051
TI  - Magnetization directions of individual nanoparticles 
AB  - The magnetization directions of individual monodomain nanoparticles as small as 5
      nanometers in diameter are determined using the Foucault method of Lorentz
      microscopy. A model is developed to explain the images and diffraction patterns
      of samarium cobalt nanoparticles as a function of the aperture shift direction.
      Thermally induced changes in the magnetization direction of superparamagnetic
      magnetite nanoparticles were observed but with a much slower rate than expected,
      due to surface anisotropy. When the time scale for magnetization reversal is much
      shorter than the data acquisition time, as in carbon-coated iron cobalt alloy
      nanoparticles, the images show an average of such thermally induced changes.

PMID- 10205052
TI  - A steric mechanism for inhibition of CO binding to heme proteins.
AB  - The crystal structures of myoglobin in the deoxy- and carbon monoxide-ligated
      states at a resolution of 1.15 angstroms show that carbon monoxide binding at
      ambient temperatures requires concerted motions of the heme, the iron, and
      helices E and F for relief of steric inhibition. These steps constitute the main
      mechanism by which heme proteins lower the affinity of the heme group for the
      toxic ligand carbon monoxide.

PMID- 10205053
TI  - Single-crystal-like diffraction data from polycrystalline materials 
AB  - A method for solving structures from powder diffraction data was developed, and
      its validity was demonstrated on three complex structures. The method uses a
      textured sample and exploits the high intensity and parallel nature of
      synchrotron radiation. In principle, crystal structures as complex as those
      routinely solved by single-crystal methods can be determined with this approach.
      For example, the as-synthesized form of the zeolite UTD-1, with 69 nonhydrogen
      atoms in the asymmetric unit, could be solved directly. With this method, a
      larger range of structural complexity becomes accessible to scientists interested
      in the structures of polycrystalline materials that cannot be grown as single
      crystals.

PMID- 10205054
TI  - Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300.
AB  - The cytokines LIF (leukemia inhibitory factor) and BMP2 (bone morphogenetic
      protein-2) signal through different receptors and transcription factors, namely
      STATs (signal transducers and activators of transcription) and Smads. LIF and
      BMP2 were found to act in synergy on primary fetal neural progenitor cells to
      induce astrocytes. The transcriptional coactivator p300 interacts physically with
      STAT3 at its amino terminus in a cytokine stimulation-independent manner, and
      with Smad1 at its carboxyl terminus in a cytokine stimulation-dependent manner.
      The formation of a complex between STAT3 and Smad1, bridged by p300, is involved
      in the cooperative signaling of LIF and BMP2 and the subsequent induction of
      astrocytes from neural progenitors.

PMID- 10205055
TI  - Dissecting and exploiting intermodular communication in polyketide synthases.
AB  - Modular polyketide synthases catalyze the biosynthesis of medicinally important
      natural products through an assembly-line mechanism. Although these megasynthases
      display very precise overall selectivity, we show that their constituent modules
      are remarkably tolerant toward diverse incoming acyl chains. By appropriate
      engineering of linkers, which exist within and between polypeptides, it is
      possible to exploit this tolerance to facilitate the transfer of biosynthetic
      intermediates between unnaturally linked modules. This protein engineering
      strategy also provides insights into the evolution of modular polyketide
      synthases.

PMID- 10205056
TI  - Aminoacyl-CoAs as probes of condensation domain selectivity in nonribosomal
      peptide synthesis.
AB  - In nonribosomal biosynthesis of peptide antibiotics by multimodular synthetases,
      amino acid monomers are activated by the adenylation domains of the synthetase
      and loaded onto the adjacent carrier protein domains as thioesters, then the
      formation of peptide bonds and translocation of the growing chain are effected by
      the synthetase's condensation domains. Whether the condensation domains have any
      editing function has been unknown. Synthesis of aminoacyl-coenzyme A (CoA)
      molecules and direct enzymatic transfer of aminoacyl-phosphopantetheine to the
      carrier domains allow the adenylation domain editing function to be bypassed.
      This method was used to demonstrate that the first condensation domain of
      tyrocidine synthetase shows low selectivity at the donor residue (D
      phenylalanine) and higher selectivity at the acceptor residue (L-proline) in the
      formation of the chain-initiating D-Phe-L-Pro dipeptidyl-enzyme intermediate.

PMID- 10205057
TI  - Functional arteries grown in vitro.
AB  - A tissue engineering approach was developed to produce arbitrary lengths of
      vascular graft material from smooth muscle and endothelial cells that were
      derived from a biopsy of vascular tissue. Bovine vessels cultured under pulsatile
      conditions had rupture strengths greater than 2000 millimeters of mercury, suture
      retention strengths of up to 90 grams, and collagen contents of up to 50 percent.
      Cultured vessels also showed contractile responses to pharmacological agents and
      contained smooth muscle cells that displayed markers of differentiation such as
      calponin and myosin heavy chains. Tissue-engineered arteries were implanted in
      miniature swine, with patency documented up to 24 days by digital angiography.

PMID- 10205058
TI  - Dense populations of a giant sulfur bacterium in Namibian shelf sediments.
AB  - A previously unknown giant sulfur bacterium is abundant in sediments underlying
      the oxygen minimum zone of the Benguela Current upwelling system. The bacterium
      has a spherical cell that exceeds by up to 100-fold the biovolume of the largest
      known prokaryotes. On the basis of 16S ribosomal DNA sequence data, these
      bacteria are closely related to the marine filamentous sulfur bacteria Thioploca,
      abundant in the upwelling area off Chile and Peru. Similar to Thioploca, the
      giant bacteria oxidize sulfide with nitrate that is accumulated to </=800
      millimolar in a central vacuole.

PMID- 10205059
TI  - SPA1, a WD-repeat protein specific to phytochrome A signal transduction.
AB  - The five members of the phytochrome photoreceptor family of Arabidopsis thaliana
      control morphogenesis differentially in response to light. Genetic analysis has
      identified a signaling pathway that is specifically activated by phytochrome A. A
      component in this pathway, SPA1 (for "suppressor of phyA-105"), functions in
      repression of photomorphogenesis and is required for normal photosensory
      specificity of phytochrome A. Molecular cloning of the SPA1 gene indicates that
      SPA1 is a WD (tryptophan-aspartic acid)-repeat protein that also shares sequence
      similarity with protein kinases. SPA1 can localize to the nucleus, suggesting a
      possible function in phytochrome A-specific regulation of gene expression.

PMID- 10205060
TI  - Control of mRNA decay by heat shock-ubiquitin-proteasome pathway.
AB  - Cytokine and proto-oncogene messenger RNAs (mRNAs) are rapidly degraded through
      AU-rich elements in the 3' untranslated region. Rapid decay involves AU-rich
      binding protein AUF1, which complexes with heat shock proteins hsc70-hsp70,
      translation initiation factor eIF4G, and poly(A) binding protein. AU-rich mRNA
      decay is associated with displacement of eIF4G from AUF1, ubiquitination of AUF1,
      and degradation of AUF1 by proteasomes. Induction of hsp70 by heat shock, down
      regulation of the ubiquitin-proteasome network, or inactivation of ubiquitinating
      enzyme E1 all result in hsp70 sequestration of AUF1 in the perinucleus-nucleus,
      and all three processes block decay of AU-rich mRNAs and AUF1 protein. These
      results link the rapid degradation of cytokine mRNAs to the ubiquitin-proteasome
      pathway.

PMID- 10205061
TI  - Regulation of mammalian circadian behavior by non-rod, non-cone, ocular
      photoreceptors.
AB  - Circadian rhythms of mammals are entrained by light to follow the daily solar
      cycle (photoentrainment). To determine whether retinal rods and cones are
      required for this response, the effects of light on the regulation of circadian
      wheel-running behavior were examined in mice lacking these photoreceptors. Mice
      without cones (cl) or without both rods and cones (rdta/cl) showed unattenuated
      phase-shifting responses to light. Removal of the eyes abolishes this behavior.
      Thus, neither rods nor cones are required for photoentrainment, and the murine
      eye contains additional photoreceptors that regulate the circadian clock.

PMID- 10205062
TI  - Regulation of the mammalian pineal by non-rod, non-cone, ocular photoreceptors.
AB  - In mammals, ocular photoreceptors mediate an acute inhibition of pineal melatonin
      by light. The effect of rod and cone loss on this response was assessed by
      combining the rd mutation with a transgenic ablation of cones (cl) to produce
      mice lacking both photoreceptor classes. Despite the loss of all known retinal
      photoreceptors, rd/rd cl mice showed normal suppression of pineal melatonin in
      response to monochromatic light of wavelength 509 nanometers. These data indicate
      that mammals have additional ocular photoreceptors that they use in the
      regulation of temporal physiology.

PMID- 10205063
TI  - Vancomycin derivatives that inhibit peptidoglycan biosynthesis without binding D
      Ala-D-Ala.
AB  - Vancomycin is an important drug for the treatment of Gram-positive bacterial
      infections. Resistance to vancomycin has begun to appear, posing a serious public
      health threat. Vancomycin analogs containing modified carbohydrates are very
      active against resistant microorganisms. Results presented here show that these
      carbohydrate derivatives operate by a different mechanism than vancomycin;
      moreover, peptide binding is not required for activity. It is proposed that
      carbohydrate-modified vancomycin compounds are effective against resistant
      bacteria because they interact directly with bacterial proteins involved in the
      transglycosylation step of cell wall biosynthesis. These results suggest new
      strategies for designing glycopeptide antibiotics that overcome bacterial
      resistance.

PMID- 10205064
TI  - Sem studies on vessels in ferns. 12. Marattiaceae, with comments on vessel
      patterns in eusporangiate ferns.
AB  - Scanning electron microscopy (SEM) of tracheary elements of roots of five species
      from four genera of Marattiaceae and of the rhizome of one species revealed
      vessel elements present in all. The secondary wall framework of perforation
      plates is the same as that of lateral wall pitting for vessel elements in all
      species. Thus, no specialization is present in perforation plates of Marattiaceae
      compared to the simplified morphology of perforation plates of some
      leptosporangiate ferns (e.g., Dryopteridaceae, Polypodiaceae, and Pteridaceae).
      The difference between lateral wall pitting and perforation plates in tracheary
      elements of Marattiaceae cannot be seen by light microscopy (in which pit
      membranes are transparent), but is evident with SEM. Diversity in structure of
      perforation plates (especially the alternation of wide and narrow perforations
      within a plate) and presence of web-like pit membrane remnants are evident.
      Vessels are widespread in both leptosporangiate and eusporangiate ferns, although
      specialization in perforation plates (e.g., bars few and more widely spaced in
      lateral wall pitting of a given vessel element) is to be expected only in ferns
      of habitats with marked fluctuation in water availability. Vessels of
      Marattiaceae lack such specializations and are thus are correlated with the mesic
      habitats characteristic for the family.

PMID- 10205065
TI  - The mechanical role of bark.
AB  - The ability of stem bark to resist bending forces was examined by testing in
      bending segments of Acer saccharum, Fraxinus americana, and Quercus robur
      branches with and without their bark. For each species, the bark contributed
      significantly to the ability of stem segments differing in age to resist bending
      forces, but its contribution was age-dependent and differed among the three
      species. The importance of the mechanical role of the bark decreased basipetally
      with increasing age of F. americana and Q. robur stem segments and was superceded
      by that of the wood for segments >= 6 yr old. A. saccharum bark was as
      mechanically important as the wood for stem segments 7 yr old but was not a
      significant stiffening agent for younger or older portions of stems. On average,
      the stiffness of the bark from all three species was 50% that of the wood.
      However, the geometric contribution to the flexural rigidity of stems made by the
      bark (i.e., the bark's second moment of area) was sufficiently large to offset
      its lower stiffness (Young's modulus) relative to that of the wood. A simple
      model is presented that shows that the bark must be as mechanically important as
      the wood when its radial thickness equals 32% that of the wood and its stiffness
      is 50% that of the wood. Based on this model, which is shown to comply with the
      data from three species purported to have stiff woods, it is evident that the
      role of the bark cannot be neglected when considering the mechanical behavior of
      juvenile woody stems subjected to externally applied bending forces.

PMID- 10205066
TI  - The effect of seed and rosette cold treatment on germination and flowering time
      in some Arabidopsis thaliana (Brassicaceae) ecotypes.
AB  - The germination and flowering responses to cold treatment were investigated in 32
      ecotypes of Arabidopsis thaliana. A month-long cold treatment at the seed stage
      decreased the time until flowering in all but one strain, whereas a 3-d cold
      treatment had little, or the opposing effect. A month-long cold treatment at the
      rosette stage also decreased the time until flowering, but was less effective
      than seed cold treatment. Seed and rosette cold treatments did not have an
      additive effect on time until flowering. Cold treatment usually increased the
      speed of germination, however no clear response patterns for the probability of
      germination were detected. These findings are discussed in relation to the life
      cycle of the plant.

PMID- 10205067
TI  - Epianthropochory in Mexican weed communities.
AB  - The diaspores of the 50 most important maize field weed species (agrestals) in a
      traditional maize-growing area of south-central Mexico (region of Puebla and
      Tlaxcala) were analyzed for morphological adaptations to long-distance dispersal.
      Adaptations to wind-dispersal were absent and to endozoochory were minimal. Most
      species had no visible adaptations and are presumably transported with mud.
      However, about one-quarter of the taxa, particularly the tall and dominant ones,
      relied at least partially on burrs with hooks or awns. The possible vectors for
      these exo- or epizoochorous species are discussed: the most likely regular
      dispersers are humans (epianthropochory). Interviews with farmers confirm this
      conclusion. Using humans as vectors allows the plant to transport relatively
      large seeds to favorable habitats (directed dispersal). The importance of this
      relatively rare dispersal adaptation in Mexican maize field weeds leads to
      questions on the origin and evolution of these agrestals.

PMID- 10205068
TI  - Floral plasticity in an iteroparous plant: the interactive effects of genotype,
      environment, and ontogeny in Campanula rapunculoides (Campanulaceae).
AB  - Phenotypic variation in 11 floral and reproductive traits was studied in cloned
      plants of Campanula rapunculoides replicated in three discrete environments.
      Using an ANOVA approach, we determined the relative influence of genotype (G),
      environment (E), G * E interaction, and ontogeny (position on the raceme) on the
      11 traits. Two traits, duration of flowering and pollen size, showed no
      significant variation. All nine remaining traits had significant genotypic
      variation, accounting for 21-38% of the total phenotypic variation. Correlations
      among variant traits in seven genotypes were predominantly positive, but several
      significant correlations in one environment changed sign or were nonsignificant
      in another environment. Ovule number was negatively correlated with most male
      function traits: the negative correlation between ovule and pollen number was
      particularly strong and consistent across environments. Six traits varied
      significantly across environments, including number of flowers, number of ovules
      per flower, and duration of the male phase, but pollen traits did not show a
      significant environmental main effect. The G * E interaction was significant for
      flower number, corolla size, nectar quality, duration of the male phase, pollen
      viability, and ovule number. The contribution of interaction variance to the
      total phenotypic variation (5-14%) was comparable to that of the environment
      alone (7-21%). Ovule number decreased in flowers on the upper part of the raceme
      by nearly 25%, but other traits did not vary significantly by floral position.
      These results suggest that (1) pollen traits are buffered against environmental
      change more than ovule number or other floral characters, (2) a male-female trade
      off exists and is complicated by ontogenic factors, (3) G * E interactions are
      common but may have small effects, and (4) specific correlation patterns among
      floral traits can be dependent upon the environment under which they develop.

PMID- 10205069
TI  - Fruit set in Styrax obassia (Styracaceae): the effect of light availability,
      display size, and local floral density.
AB  - Maternal reproductive success was examined in Styrax obassia (Styracaceae), a
      bumble-bee pollinated mass-flowering tree in a cool-temperate deciduous forest in
      northern Japan. The effects of flower number on the success of individual flowers
      at three levels (inflorescence, individual, and population) were considered.
      During 1995 and 1996, variations in size, light availability to branches, floral
      display size, and fruit set were monitored in 37 out of 211 individual S. obassia
      trees in a 4-ha forest plot. In addition, the locations of the 211 trees in this
      plot were mapped and the number of inflorescences in each tree was counted. A
      multiple regression analysis showed that flower number per inflorescence and
      inflorescence number per individual had negative effects on fruit set, and
      inflorescence number of aggregated clumps of flowering trees, tree size, and
      light resource had positive effects on fruit set although significant level were
      marginal. It is concluded that pollinator attraction may occur not at the
      individual tree level, but at the level of a clump of flowering trees. It is also
      suggested that geitonogamy increased with inflorescence number of tree and
      inflorescence size and that resource limitation was related to the light
      condition and variation of tree size.

PMID- 10205070
TI  - The pollination ecology of buzz-pollinated Rhexia virginica (Melastomataceae).
AB  - We examined the function of floral traits associated with buzz pollination
      through studies of Rhexia virginica (Melastomataceae) in the Muskoka region of
      Ontario, Canada. Controlled pollinations demonstrated that the species is self
      compatible, but dependent on insects for pollen transfer. Bumble bees made 82 and
      90% of observed insect visits to R. virginica in 1996 and 1997, respectively, and
      effectively buzzed flowers. Buzz pollination did not appear to be highly
      "specialized" since various species of bumble bee were capable of pollination,
      and pollen transfer efficiency appeared to be relatively low. Experimental
      manipulations provided little support for the hypothesis that the yellow color of
      melastome anthers mimics abundant pollen, thereby deceiving pollinators to visit
      regardless of whether most pollen has been removed. Fruit set averaged 52.6%
      among populations, owing largely to infrequent pollinator visits and pollen
      limitation. Flowers of R. virginica were infertile after a single day of
      anthesis, but petals were subsequently maintained for 1-2 d and stamens underwent
      a color change from bright yellow to red. Second-day flowers may function to
      increase floral display size and hence fertility, without a concomitant increase
      in pollen discounting. Studies of bumble bee foraging behavior and correlates of
      seed set provided indirect support for this hypothesis.

PMID- 10205071
TI  - Life history variation in gametophyte populations of the moss Ceratodon purpureus
      (Ditrichaceae).
AB  - The life cycles of mosses and other bryophytes are unique among land plants in
      that the haploid gametophyte stage is free-living and the diploid sporophyte
      stage is ephemeral and completes its development attached to the maternal
      gametophyte. Despite predictions that populations of haploids might contain low
      levels of genetic variation, moss populations are characterized by substantial
      variation at isozyme loci. The extent to which this is indicative of ecologically
      important life history variation is, however, largely unknown. Gametophyte plants
      from two populations of the moss Ceratodon purpureus were grown from single-spore
      isolates in order to assess variation in growth rates, biomass accumulation, and
      reproductive output. The data were analyzed using a nested analysis of variance,
      with haploid sib families (gametophytes derived from the same sporophyte) nested
      within populations. High levels of life history variation were observed within
      both populations, and the populations differed significantly in both growth and
      reproductive characteristics. Overall gametophytic sex ratios did not depart
      significantly from 1:1 within either population, but there was significant
      variation among families in both populations for progeny sex ratio. Some families
      produced predominantly male gametophytes, while others yielded predominantly
      females. Because C. purpureus has a chromosomal mechanism of sex determination,
      these observations suggest differential (but unpredictable) germination of male
      and female spores. Life history observations showed that male and female
      gametophytes are dimorphic in size, maturation rates, and reproductive output.

PMID- 10205072
TI  - Morphological variation and the process of domestication of Stenocereus stellatus
      (Cactaceae) in Central Mexico.
AB  - Morphological variation was analyzed in wild, managed in situ, and cultivated
      populations of the columnar cactus Stenocereus stellatus in central Mexico. The
      purpose was to evaluate whether morphological divergence between manipulated and
      wild populations has resulted from domestication processes. Variation of 23
      morphological characters was analyzed among 324 individuals from 19 populations
      of the Tehuacan Valley and La Mixteca Baja. Multivariate statistical analyses
      were used to group individuals and populations according to their morphological
      similarity. Individuals grouped according to the way of management and fruit
      characteristics were the most relevant for grouping. Within each region, sweet
      fruits with pulp colors other than red were more frequent in cultivated
      populations, where fruits were also larger, contained more and bigger seeds, and
      had thinner peel and fewer spines than fruits from wild individuals. Phenotypes
      common in managed in situ and cultivated populations generally occur in the wild
      but in lower frequencies. Artificial selection has thus operated by enhancing and
      maintaining desirable rare phenotypes in managed in situ and cultivated
      populations, causing divergent patterns of morphological variation from wild
      populations. Cultivation has caused the strongest level of divergence, but
      divergence has also been significant with management of wild populations in situ.

PMID- 10205073
TI  - Reproductive biology and the process of domestication of the columnar cactus
      Stenocereus Stellatus in Central Mexico.
AB  - Pollination biology, breeding system, and floral phenology of the columnar cactus
      Stenocereus stellatus were studied in wild, wild managed in situ and cultivated
      populations of central Mexico, in order to examine whether these aspects have
      been modified under domestication and whether they determine reproductive
      barriers between wild and manipulated individuals. Individuals of both wild and
      manipulated populations are self-incompatible, indicating that artificial
      selection has not modified the breeding system. Their pollination biology is also
      similar. Anthesis is mainly nocturnal, with a peak of nectar production between
      0200 and 0400 when the stigma presents maximum turgidity. Nocturnal visitors are
      the effective pollinators. Nearly 75% of flowers exposed for nocturnal
      pollination set fruit, while none of the flowers exposed for diurnal pollination
      produced fruits. The bats Leptonycteris curasoae, L. nivalis, and Choeronycteris
      mexicana (Glossophaginae) are the most likely pollinators, and their time of
      foraging is synchronized with the time of nectar production and stigma
      receptivity in S. stellatus. Bats potentially move pollen over a considerable
      distance, so there is apparently no spatial isolation to prevent pollen exchange
      between wild and cultivated populations. Phenological studies showed that there
      are also no apparent temporal barriers. However, manual cross pollination failed
      between some domesticated and wild phenotypes, suggesting that gene flow between
      wild and cultivated populations might be limited by pollen incompatibility.

PMID- 10205074
TI  - Evolution of a new ecotype of Spartina alterniflora (Poaceae) in San Francisco
      Bay, California, USA.
AB  - We report the discovery and spread of a dwarf ecotype of Spartina alterniflora in
      San Francisco Bay. Relative to typical S. alterniflora, this dwarf ecotype has
      one-fifth the tiller height (~21 cm), tenfold the tiller density (~4000
      tillers/m(2)), and is restricted to growth in the upper intertidal zone.
      Chromosome counts of the dwarfs are identical to typical smooth cordgrass (2n =
      62), and smooth cordgrass-specific random amplified DNA markers confirm the
      species identity of the dwarf. Field-collected clonal fragments of the dwarf
      grown for 2 yr under high-nutrient conditions maintained the dwarf syndrome, as
      did plants grown from the seed of a dwarf. The dwarf condition is not caused by
      endophytic fungi. The first dwarf smooth cordgrass patch was discovered in 1991,
      and by 1996 five separate dwarf patches had appeared within 200 m of the
      original. Since 1991, total area covered by the dwarf ecotype has increased
      sixfold to 140 m(2). The ecological range of the dwarf smooth cordgrass ecotype
      is similar to that of S. patens, a competitor on the Atlantic coast. We suggest
      that the absence of S. patens from most of San Francisco Bay has allowed the
      dwarf ecotype of smooth cordgrass to survive and spread.

PMID- 10205075
TI  - Mycorrhizal status of the genus Carex (Cyperaceae).
AB  - The Cyperaceae have generally been considered nonmycorrhizal, although recent
      evidence suggests that mycotrophy may be considerably more widespread among
      sedges than was previously realized. This study surveyed 23 species of Carex
      occurring in upland and wetland habitats in northeastern Illinois. Mycorrhizal
      infection by arbuscular fungi was found in the roots of 16 species of Carex and
      appears to occur in response to many factors, both environmental and
      phylogenetic. While some species appear to be obligately nonmycorrhizal, edaphic
      influences may be responsible for infection in others. In five of the seven Carex
      species that were nonmycorrhizal, a novel root character, the presence of bulbous
      based root hairs, was identified. The taxonomically patchy distribution of the
      distinctive root hair trait suggests that these structures may have evolved
      several times within the genus. Evidence of multiple independent origins of the
      root hair trait lends support to the hypothesis that root hairs represent an
      adaptation to nonmycotrophy. Although taxonomic position does seem to be of
      importance in determining the mycorrhizal dependence of sedges, the pattern may
      be a patchwork of both mycorrhizal clades and clades that have adapted to the
      nonmycorrhizal state.

PMID- 10205076
TI  - RAPDs and noncoding chloroplast DNA reveal a single origin of the cultivated
      Allium fistulosum from A. altaicum (Alliaceae).
AB  - The origin of the crop species Allium fistulosum (bunching onion) and its
      relation to its wild relative A. altaicum were surveyed with a restriction
      fragment length polymorphism (RFLP) analysis of five noncoding cpDNA regions and
      with a random amplified polymorhic DNA (RAPD) analysis of nuclear DNA. Sixteen
      accessions of A. altaicum, 14 accessions of A. fistulosum, representing the
      morphological variability of the species, and five additional outgroup species
      from Allium section Cepa were included in this study. The RFLP analysis detected
      14 phylogenetically informative character transformations, whereas RAPD revealed
      126 polymorphic fragments. Generalized parsimony, neighbor-joining analysis of
      genetic distances, and a principal co-ordinate analysis were able to distinguish
      the two species, but only RAPD data allowed clarification of the
      interrelationship of the two taxa. The main results of this investigation were:
      (1) A. fistulosum is of monophyletic origin, and (2) A. fistulosum originated
      from an A. altaicum progenitor, making A. altaicum a paraphyletic species.
      Compared with A. altaicum the cultivated accessions of the bunching onion show
      less genetic variability, a phenomenon that often occurs in crop species due to
      the severe genetic bottleneck of domestication. Allium altaicum and A. fistulosum
      easily hybridize when grown together, and most garden-grown material is of recent
      hybrid origin.

PMID- 10205077
TI  - The phylogenetic position of Carex section Phyllostachys and its implications for
      phylogeny and subgeneric circumscription in Carex (Cyperaceae).
AB  - Wide speculation surrounds the origin and phylogenetic relationships of the most
      highly reduced sections in the genus Carex. In order to gain a better
      understanding of phylogeny in Carex, the relationship of the reduced sect.
      Phyllostachys to 12 putatively related sections, representing all four subgenera
      (Primocarex, Indocarex, Carex, Vignea), was inferred from sequences of the ITS
      (internal transcribed spacer) region of nrDNA. Phylogenetic reconstructions
      identified two main clades: (1) a "compound" clade composed of sections from
      subg. Indocarex, Primocarex, and a portion of subg. Carex, and (2) a "reduced"
      clade consisting of sections from subg. Carex (Phyllostachys) and Primocarex
      (Filifoliae and Firmiculmes). Subgenus Indocarex was paraphyletic within the
      "compound" clade supporting classifications that have merged it within a wider
      subg. Indocarex/Carex/Primocarex line. Subgenus Primocarex was polyphyletic. This
      result was consistent with theories that extreme reduction has occurred along
      several different evolutionary lines in Carex. Phylogenetic theories inferred
      from the presence or abnormal growth of the rachilla were not supported by tree
      topologies. Difficult sectional circumscriptions, such as the separation of
      sections Laxiflorae and Careyanae, were strongly upheld by sequence data. The ITS
      region is an effective tool for defining sectional limits and for estimating
      relationships among sections in Carex, but does not provide enough phylogenetic
      information to fully resolve relationships below the sectional level.

PMID- 10205078
TI  - Molecular phylogenetics of Fouquieriaceae: evidence from nuclear rDNA ITS
      studies.
AB  - Molecular sequence data from the 18S-26S rDNA internal transcribed spacer (ITS)
      region support the monophyly of Fouquieria sensu lato (Fouquieriaceae) and the
      three subgenera (subg. Fouquieria, subg. Bronnia, subg. Idria) previously
      recognized within it. Resolution within subg. Fouquieria differs somewhat between
      parsimony and maximum likelihood (ML) trees. Section Fouquieria and sect.
      Ocotilla within subg. Fouquieria are not well supported as monophyletic groups.
      Uncertainty regarding placement of the root within Fouquieriaceae makes
      discussion of character evolution within the family difficult. Three root
      positions are consistent with rate-constant evolution of ITS sequences: (1) along
      the branch to subg. Idria, (2) along the branch to subg. Bronnia, and (3) along
      the branch to subg. Fouquieria. The first root position listed is equivalent to
      an outgroup rooting. The third root position listed is equivalent to a midpoint
      rooting. Of the three root positions above, only the third is along a branch that
      may be sufficiently long to act as a long-branch attractor. The first two root
      positions would result in character reconstruction suggesting that succulent
      growth forms and white floral pigmentation are ancestral within the family, with
      shifts to woody growth forms and to red floral pigmentation. The third root
      position results in equivocal reconstruction of the ancestral growth form,
      equivocal reconstruction of ancestral floral pigmentation in parsimony trees, and
      a suggestion of white floral pigmentation as ancestral in ML trees. Two previous
      hypotheses of polyploid origins are compatible with the molecular data presented
      here: (1) origin of the tetraploid F. diguetii from F. macdougalii, and (2)
      allopolyploid origin of the hexaploid F. burragei from the tetraploid F. diguetii
      and a diploid species similar to F. splendens. Direct descent of the hexaploid F.
      columnaris from the subg. Bronnia lineage is not supported by our data. An
      amphiploid origin of F. columnaris involving a member of the subg. Bronnia
      lineage and an extinct taxon outside subg. Bronnia, however, cannot be ruled out.

PMID- 10205079
TI  - Phylogenetic relationships in Lupinus (Fabaceae: Papilionoideae) based on
      internal transcribed spacer sequences (ITS) of nuclear ribosomal DNA.
AB  - Internal transcribed spacer (ITS) sequences of nuclear ribosomal DNA from 44 taxa
      of the genus Lupinus and five outgroup taxa were used for phylogenetic analysis.
      Lupinus appears as a strongly supported monophyletic genus, which is
      unambiguously part of the Genisteae. The lupines are distributed into five main
      clades in general accordance with their geographical origin. In the Old World,
      almost all the recognized taxonomic units are well resolved. The ITS data reveal
      an unexpectedly close relationship between the diverse sections Angustifoli and
      Lutei. The ITS results suggest a geographical division between the western New
      World lupines and the eastern ones. They also indicate the presence of some
      moderately to strongly supported groups of taxa, such as the Microcarpi-Pusilli
      group, the L. spariflorus-L. arizonicus group, the L. mexicanus-L. elegans group
      in the western New World, and the notable L. multiflorus-L. paraguariensis group
      in the eastern New World. The latter group strongly suggests that the eastern
      South American compound- and simple-leaved perennial lupines derive from a common
      ancestor. However, apart from some exceptions, relationships within the genus
      still remain largely unresolved based on ITS data. The lack of resolution at the
      base of the genus is suggestive of a rapid initial radiation of the lupines
      subsequent to the dispersal of their common ancestor. Relative rate tests
      demonstrate the presence of rate heterogeneity of ITS sequences within Lupinus.
      In many pairwise comparisons between taxa, substitution rate inequalities are
      correlated with the habit (annual, perennial), suggesting some role for the
      generation time effects in the evolutionary history of lupines.

PMID- 10205080
TI  - Tuberous sclerosis.

PMID- 10205082
TI  - Reconstruction of dislocated hips in children with cerebral palsy.

PMID- 10205081
TI  - Tackling health inequalities in primary care.

PMID- 10205083
TI  - Improving the training of SHOs.

PMID- 10205084
TI  - Do dietary lectins cause disease?

PMID- 10205085
TI  - Ireland announces national breast screening programme.

PMID- 10205086
TI  - US couple files malpractice lawsuit against doctor for embryo mix up.

PMID- 10205087
TI  - First clinical performance indicators for wales show wide variation 

PMID- 10205090
TI  - Spain launches campaign to stop health professionals smoking.

PMID- 10205089
TI  - Tobacco memos reveal efforts to disrupt smoking cessation.

PMID- 10205088
TI  - Department of health changes advice on third generation pills.

PMID- 10205091
TI  - Ovarian cancer screening may increase survival 

PMID- 10205092
TI  - Researchers find genetic basis for susceptibility to mycobacteria 

PMID- 10205094
TI  - NHS "cannot cope," says tory 

PMID- 10205093
TI  - Kosovo refugees spared epidemics so far.

PMID- 10205095
TI  - Long term displacement raises new health needs.

PMID- 10205097
TI  - Health project targets women and children in indonesia 

PMID- 10205096
TI  - Free eye tests introduced for people over 60 in england and wales 

PMID- 10205098
TI  - Endostatin may stop the progression of atherosclerosis 

PMID- 10205100
TI  - Relation of Chlamydia pneumoniae serology to mortality and incidence of ischaemic
      heart disease over 13 years in the caerphilly prospective heart disease study.
AB  - OBJECTIVES: To investigate the effect of Chlamydia pneumoniae infection on future
      development of ischaemic heart disease and mortality. DESIGN: Prospective
      longitudinal study. SETTING: Caerphilly, South Wales. SUBJECTS: Plasma specimens
      were collected during 1979-83 from 1773 men aged 45-59 years. These were tested
      for IgG and IgA antibodies to C pneumoniae (TW183) by microimmunofluorescence.
      OUTCOME MEASURES: 13 year mortality and incident ischaemic heart disease events
      were ascertained from death certificates, hospital records, and
      electrocardiographic changes at follow up every 4 to 5 years. RESULTS: 642 men
      (36.2%) had IgG antibodies at a titre of >/=1 in 16, of whom 362 (20.4% of all
      men) also had detectable IgA antibodies. The prevalence of ischaemic heart
      disease (a history of past or current disease) at entry was similar at all IgG
      antibody titres but was positively related to IgA antibody titre. IgA antibody
      titre was positively correlated with plasma viscosity but not with other
      cardiovascular risk factors. Incidence of ischaemic heart disease was not
      associated with either IgG antibody titre or IgA antibody titre, but there were
      stronger and significant relations of IgA antibodies with all cause mortality and
      fatal ischaemic heart disease, which persisted after adjustment for conventional
      cardiovascular risk factors. The odds ratios associated with detectable IgA
      antibodies were 1.07 (95% confidence interval 0.75 to 1.53) for all incident
      ischaemic heart disease, 1. 83 (1.17 to 2.85) for fatal ischaemic heart disease,
      and 1.50 (1.10 to 2.04) for all cause mortality. CONCLUSION: This is the first
      prospective demonstration of an association between IgA antibodies to C
      pneumoniae, a putative marker of chronic infection, and subsequent risk of death
      from ischaemic heart disease. In contrast to earlier case-control studies, IgG
      antibodies were not associated with either prevalent or incident ischaemic heart
      disease.

PMID- 10205099
TI  - Double blind, randomised study of continuous terbinafine compared with
      intermittent itraconazole in treatment of toenail onychomycosis. The LION Study
      Group.
AB  - OBJECTIVE: To compare the efficacy and safety of continuous terbinafine with
      intermittent itraconazole in the treatment of toenail onychomycosis. DESIGN:
      Prospective, randomised, double blind, double dummy, multicentre, parallel group
      study lasting 72 weeks. SETTING: 35 centres in six European countries. SUBJECTS:
      496 patients aged 18 to 75 years with a clinical and mycological diagnosis of
      dermatophyte onychomycosis of the toenail. INTERVENTIONS: Study patients were
      randomly divided into four parallel groups to receive either terbinafine 250 mg a
      day for 12 or 16 weeks (groups T12 and T16) or itraconazole 400 mg a day for 1
      week in every 4 weeks for 12 or 16 weeks (groups I3 and I4). MAIN OUTCOME
      MEASURES: Assessment of primary efficacy at week 72 was mycological cure, defined
      as negative results on microscopy and culture of samples from the target toenail.
      RESULTS: At week 72 the mycological cure rates were 75.7% (81/107) in the T12
      group and 80. 8% (80/99) in the T16 group compared with 38.3% (41/107) in the I3
      group and 49.1 % (53/108) in the I4 group. All comparisons (T12 v I3, T12 v I4,
      T16 v I3, T16 v I4) showed significantly higher cure rates in the terbinafine
      groups (all P<0.0001). Also, all secondary clinical outcome measures were
      significantly in favour of terbinafine at week 72. There were no differences in
      the number or type of adverse events recorded in the terbinafine or itraconazole
      groups. CONCLUSION: Continuous terbinafine is significantly more effective than
      intermittent itraconazole in the treatment of patients with toenail
      onychomycosis.

PMID- 10205101
TI  - Low dose subcutaneous adrenaline to prevent acute adverse reactions to antivenom
      serum in people bitten by snakes: randomised, placebo controlled trial.
AB  - OBJECTIVE: To assess the efficacy and safety of low dose adrenaline injected
      subcutaneously to prevent acute adverse reactions to polyspecific antivenom serum
      in patients admitted to hospital after snake bite. DESIGN: Prospective, double
      blind, randomised, placebo controlled trial. SETTING: District general hospital
      in Sri Lanka. SUBJECTS: 105 patients with signs of envenomation after snake bite,
      randomised to receive either adrenaline (cases) or placebo (controls) immediately
      before infusion of antivenom serum. INTERVENTIONS: Adrenaline 0.25 ml (1:1000).
      MAIN OUTCOME MEASURES: Development of acute adverse reactions to serum and side
      effects attributable to adrenaline. RESULTS: 56 patients (cases) received
      adrenaline and 49 (controls) received placebo as pretreatment. Six (11%)
      adrenaline patients and 21 (43%) control patients developed acute adverse
      reactions to antivenom serum (P=0.0002). Significant reductions in acute adverse
      reactions to serum were also seen in the adrenaline patients for each category of
      mild, moderate, and severe reactions. There were no significant adverse effects
      attributable to adrenaline. CONCLUSIONS: Use of 0.25 ml of 1:1000 adrenaline
      given subcutaneously immediately before administration of antivenom serum to
      patients with envenomation after snake bite reduces the incidence of acute
      adverse reactions to serum.

PMID- 10205102
TI  - Mortality from dementia in occupations at risk of exposure to bovine spongiform
      encephalopathy: analysis of death registrations.

PMID- 10205104
TI  - You can but try 

PMID- 10205103
TI  - Study of infectious intestinal disease in England: rates in the community,
      presenting to general practice, and reported to national surveillance. The
      Infectious Intestinal Disease Study Executive.
AB  - OBJECTIVE: To establish the incidence and aetiology of infectious intestinal
      disease in the community and presenting to general practitioners. Comparison with
      incidence and aetiology of cases reaching national laboratory based surveillance.
      DESIGN: Population based community cohort incidence study, general practice based
      incidence studies, and case linkage to national laboratory surveillance. SETTING:
      70 general practices throughout England. PARTICIPANTS: 459 975 patients served by
      the practices. Community surveillance of 9776 randomly selected patients. MAIN
      OUTCOME MEASURES: Incidence of infectious intestinal disease in community and
      reported to general practice. RESULTS: 781 cases were identified in the community
      cohort, giving an incidence of 19.4/100 person years (95% confidence interval
      18.1 to 20.8). 8770 cases presented to general practice (3.3/100 person years
      (2.94 to 3.75)). One case was reported to national surveillance for every 1.4
      laboratory identifications, 6.2 stools sent for laboratory investigation, 23
      cases presenting to general practice, and 136 community cases. The ratio of cases
      in the community to cases reaching national surveillance was lower for bacterial
      pathogens (salmonella 3.2:1, campylobacter 7.6:1) than for viruses (rotavirus
      35:1, small round structured viruses 1562:1). There were many cases for which no
      organism was identified. CONCLUSIONS: Infectious intestinal disease occurs in 1
      in 5 people each year, of whom 1 in 6 presents to a general practitioner. The
      proportion of cases not recorded by national laboratory surveillance is large and
      varies widely by microorganism. Ways of supplementing the national laboratory
      surveillance system for infectious intestinal diseases should be considered.

PMID- 10205105
TI  - Fortnightly review: oral cancer.

PMID- 10205106
TI  - Lesson of the week: orbital trauma. Do not blow your nose.

PMID- 10205108
TI  - Illegal practice of medicine by an M.D 

PMID- 10205107
TI  - Evidence based case report: use of prostaglandins to induce labour in women with
      a caesarean section scar.

PMID- 10205109
TI  - ABC of labour care: preterm labour and premature rupture of membranes.

PMID- 10205110
TI  - Can children and young people consent to be tested for adult onset genetic
      disorders?

PMID- 10205111
TI  - The World Bank and world health: focus on South Asia-I: Bangladesh.

PMID- 10205112
TI  - Should women who elect to have caesarean sections pay for them?

PMID- 10205113
TI  - Is general practice in need of a career structure? Current training structure has
      many strengths.

PMID- 10205114
TI  - Effects of the Heartbeat Wales programme. Programme that originated in Finland
      should be adopted.

PMID- 10205115
TI  - The Di Bella multitherapy trial. Randomised controlled trials may not always be
      absolutely needed.

PMID- 10205116
TI  - Randomised controlled trials are important.

PMID- 10205117
TI  - Height and risk of cancer. Survival selection bias should have been ruled out.

PMID- 10205118
TI  - Practical problems in recruiting patients with schizophrenia into randomised
      controlled trials.

PMID- 10205119
TI  - Employing staff on long term contracts is important for RCTs.

PMID- 10205120
TI  - Bullied children are picked on for their vulnerability.

PMID- 10205121
TI  - More financial resources must be provided for multidrug resistant TB.

PMID- 10205122
TI  - Some growth promoters in animals do confer antimicrobial resistance in humans.

PMID- 10205123
TI  - Hyperbaric oxygen therapy. Combination with radiotherapy in cancer is of proved
      benefit but rarely used.

PMID- 10205124
TI  - Many manoeuvres with yo yos can be dangerous to teeth.

PMID- 10205126
TI  - Robert bransby zachary 

PMID- 10205125
TI  - Ingestion of mouthwash by children. Child proof caps are needed to prevent
      deaths.

PMID- 10205127
TI  - Consultants receive guidance on clinical governance 

PMID- 10205128
TI  - Rationing-talk and action in health care 

PMID- 10205129
TI  - American surgery, An illustrated history 

PMID- 10205131
TI  - Bookcase 

PMID- 10205130
TI  - Health, civilization and the state: A history of public health from ancient to
      modern times 

PMID- 10205132
TI  - A prayer from the dying:

PMID- 10205133
TI  - Website of the week 

PMID- 10205134
TI  - Will clinical governance make a difference? 

PMID- 10205135
TI  - All change 

PMID- 10205136
TI  - Terbinafine is best treatment for fungal nail infection 

PMID- 10205137
TI  - Chlamydia pneumoniae antibodies may predict fatal heart disease 

PMID- 10205138
TI  - Adrenaline prevents acute adverse reactions to antivenom after snake bite 

PMID- 10205139
TI  - No increase in mortality found among occupations exposed to BSE 

PMID- 10205140
TI  - National surveillance misses most infectious intestinal disease 

PMID- 10205141
TI  - Clinical genetics should not impose a younger age limit on testing 

PMID- 10205142
TI  - Correlation between myofilament response to Ca2+ and altered dynamics of
      contraction and relaxation in transgenic cardiac cells that express beta
      tropomyosin.
AB  - We compared the dynamics of the contraction and relaxation of single myocytes
      isolated from nontransgenic (NTG) mouse hearts and from transgenic (TG-beta-Tm)
      mouse hearts that overexpress the skeletal isoform of tropomyosin (Tm). Compared
      with NTG controls, TG-beta-Tm myocytes showed significantly reduced maximal rates
      of contraction and relaxation with no change in the extent of shortening. This
      result indicated that the depression in contraction dynamics determined in TG
      beta-Tm isolated hearts is intrinsic to the cells. To further investigate the
      effect of Tm isoform switching on myofilament activity and regulation, we
      measured myofilament force and ATPase rate as functions of pCa (-log of [Ca2+]).
      Compared with controls, force generated by myofilaments from TG-beta-Tm hearts
      and myofibrillar ATPase activity were both more sensitive to Ca2+. However, the
      shift in pCa50 (half-maximally activating pCa) caused by changing sarcomere
      length from 1.8 to 2.4 microm was not significantly different between NTG and TG
      beta-Tm fiber preparations. To test directly whether isoform switching affected
      the economy of contraction, force versus ATPase rate relationships were measured
      in detergent-extracted fiber bundles. In both NTG and TG-beta-Tm preparations,
      force and ATPase rate were linear and identically correlated, which indicated
      that crossbridge turnover was unaffected by Tm isoform switching. However,
      detergent extracted fibers from TG-beta-Tm demonstrated significantly less
      maximum tension and ATPase activity than NTG controls. Our results provide the
      first evidence that the Tm isoform population modulates the dynamics of
      contraction and relaxation of single myocytes by a mechanism that does not alter
      the rate-limiting step of crossbridge detachment. Our results also indicate that
      differences in sarcomere-length dependence of activation between cardiac and
      skeletal muscle are not likely due to differences in the isoform population of
      Tm.

PMID- 10205143
TI  - Overexpression of insulin-like growth factor-1 attenuates the myocyte renin
      angiotensin system in transgenic mice.
AB  - Constitutive overexpression of insulin-like growth factor-1 (IGF-1) in myocytes
      protects them from apoptosis and interferes with myocyte hypertrophy in the
      normal and pathological heart. Conversely, angiotensin II (Ang II) triggers cell
      death and promotes myocyte hypertrophy. Moreover, activation of p53 upregulates
      the cellular renin-angiotensin system (RAS). Therefore, IGF-1 overexpression in
      FVB.Igf+/- mice may downregulate the local RAS through the attenuation of p53 and
      p53-inducible genes. On this basis, p53 DNA binding activity to angiotensinogen
      (Aogen), bax, and the AT1 receptor was determined in left ventricular myocytes
      from FVB.Igf-/- and FVB.Igf+/- mice. The quantity of Bax, Bcl-2, Aogen, and AT1
      receptor in these cells was evaluated. The presence of Mdm2-p53 complexes was
      also established. Finally, Ang II levels in myocytes were measured. Upregulation
      of IGF-1 in myocytes was associated with a protein-to-protein interaction between
      Mdm2 and p53, which attenuated p53 transcriptional activity for bax, Aogen, and
      AT1 receptor. Similarly, the amount of Bax, Aogen, and AT1 receptor proteins in
      these cells decreased. In contrast, the expression of Bcl-2 remained constant.
      The downregulation of Aogen in myocytes from FVB.Igf+/- mice was characterized by
      a reduction in Ang II. In conclusion, IGF-1 negatively influences the myocyte RAS
      through the upregulation of Mdm2 and its binding to p53. This may represent the
      molecular mechanism responsible for the effects of IGF-1 on cell viability and
      myocyte hypertrophy in the nonpathological and pathological heart in vivo.

PMID- 10205144
TI  - Chloride channel inhibition blocks the protection of ischemic preconditioning and
      hypo-osmotic stress in rabbit ventricular myocardium.
AB  - The objective of this study was to examine the role of chloride (Cl-) channels in
      the myocardial protection of ischemic preconditioning (IP). Isolated rabbit
      ventricular myocytes were preconditioned with 10-minute simulated ischemia (SI)
      and 20-minute simulated reperfusion (SR) or not preconditioned (control). The
      myocytes then received 180-minute SI or 45-minute SI/120-minute SR.
      Indanyloxyacetic acid 94 (IAA-94, 10 micromol/L) or 5-nitro-2-(3
      phenylpropylamino)benzoic acid (NPPB, 1 micromol/L) was administered before IP or
      before SI or SI/SR to inhibit Cl- channels. Electrophysiological studies indicate
      that these drugs, at the concentrations used, selectively abolished Cl- currents
      activated under hypo-osmotic conditions (215 versus 290 mOsm). IP significantly
      (P<0.001) reduced the percentage of dead myocytes after 60-minute (30.8+/-1.3%,
      mean+/-SEM), 90-minute (35.3+/-1.3%), and 120-minute (39.2+/-1.7%) SI compared
      with controls (44.7+/-1.6%, 54.5+/-1.3%, and 58.9+/-1.8%, respectively) and after
      45-minute SI/120-minute SR (36.3+/-0.6%) compared with control (56.6+/-2.2%).
      Hypo-osmotic stress also produced protection similar to IP. IAA-94 or NPPB
      abolished the protection of both IP and hypo-osmotic stress. In buffer-perfused
      rabbit hearts preconditioned with three 5-minute ischemia/10-minute reperfusion
      cycles given before the 40-minute long ischemia and 60-minute reperfusion, IP
      significantly (P<0.0001) reduced infarct size (IP+vehicle, 4.7+/-0.9%, versus
      control+vehicle, 26.6+/-3.3%; mean+/-SEM). Again, IAA-94 or NPPB abolished the
      protection of IP. Our results implicate Cl- channels in the IP protection of the
      myocardium against ischemic/reperfusion injury and demonstrate that hypo-osmotic
      stress is capable of preconditioning cardiomyocytes.

PMID- 10205145
TI  - Molecular mechanisms underlying ionic remodeling in a dog model of atrial
      fibrillation.
AB  - The rapid atrial rate during atrial fibrillation (AF) decreases the ionic current
      density of transient outward K+ current, L-type Ca2+ current, and Na+ current,
      thereby altering cardiac electrophysiology and promoting arrhythmia maintenance.
      To assess possible underlying changes in cardiac gene expression, we applied
      competitive reverse transcriptase-polymerase chain reaction to quantify mRNA
      concentrations in dogs subjected to 7 (group P7 dogs) or 42 (group P42 dogs) days
      of atrial pacing at 400 bpm and in sham controls. Rapid pacing reduced mRNA
      concentrations of Kv4.3 (putative gene encoding transient outward K+ current; by
      60% in P7 and 74% in P42 dogs; P<0.01 and P<0.001, respectively, versus shams),
      the alpha1c subunit of L-type Ca2+ channels (by 57% in P7 and 72% in P42 dogs;
      P<0.01 versus shams for each) and the alpha subunit of cardiac Na+ channels (by
      18% in P7 and 42% in P42; P=NS and P<0.01, respectively, versus shams) genes. The
      observed changes in ion channel mRNA concentrations paralleled previously
      measured changes in corresponding atrial ionic current densities. Atrial
      tachycardia did not affect mRNA concentrations of genes encoding delayed or
      Kir2.1 inward rectifier K+ currents (of which the densities are unchanged by
      atrial tachycardia) or of the Na+,Ca2+ exchanger. Western blot techniques were
      used to quantify protein expression for Kv4.3 and Na+ channel alpha subunits,
      which were decreased by 72% and 47%, respectively, in P42 dogs (P<0.001 versus
      control for each), in a manner quantitatively similar to measured changes in mRNA
      and currents, whereas Na+,Ca2+ exchanger protein concentration was unchanged. We
      conclude that chronic atrial tachycardia alters atrial ion channel gene
      expression, thereby altering ionic currents in a fashion that promotes the
      occurrence of AF. These observations provide a potential molecular basis for the
      self-perpetuating nature of AF.

PMID- 10205147
TI  - Analysis of the presence and physiological relevance of subconducting states of
      Connexin43-derived gap junction channels in cultured human corporal vascular
      smooth muscle cells.
AB  - Subconductance states are a commonly observed feature of gap junction channels.
      Their overt frequency and consistent appearance in both single and multichannel
      records have led to speculation that they might be of physiological importance in
      terms of altering the rate of small solute transfer from cell to cell. Among the
      connexin gene family, connexin43 (Cx43) is the most ubiquitous connexin that has
      been shown to generate subconductive states. Therefore, it was the explicit aim
      of this investigation to more fully evaluate the potential contribution of human
      Cx43-derived subconducting states to intercellular communication in cultured
      human corporal vascular smooth muscle cells. To determine the weight of
      subconductive states in our records, we analyzed amplitude histograms of
      multichannel and single-channel data during the application of transjunctional
      voltages larger than expected for physiological conditions but still smaller than
      transjunctional voltages known to induce lower conductive states (Vo>Vj). The
      data clearly indicated that the subconducting states occupy only a small fraction
      of the total channel open time. This was reflected by the fact that the average
      open probability for the subconductive state(s) determined from the 9 records
      analyzed was approximately 2%. Closer inspection of the data revealed that the
      frequency of subconductive states was actually higher than the frequency of the
      main state conductance. In summary, recording conditions sufficient for
      evaluation of the intrinsic gating characteristics of human Cx43-derived gap
      junction channels have been used. Under these conditions, our data clearly
      indicate that despite their greater frequency, the duration of subconductance
      events is so short relative to the main state duration as to render them
      physiologically insignificant.

PMID- 10205146
TI  - Thrombopoietin stimulates endothelial cell motility and neoangiogenesis by a
      platelet-activating factor-dependent mechanism.
AB  - In this study, we demonstrate that human umbilical cord vein-derived endothelial
      cells (HUVECs) expressed c-Mpl, the thrombopoietin (TPO) receptor, and that TPO
      activates HUVECs in vitro, as indicated by directional migration, synthesis of 1
      alkyl-/1-acyl-platelet-activating factor (PAF) and interleukin-8 (IL-8), and
      phosphorylation of the signal transducers and activators of transcription (STAT)
      STAT1 and STAT5B. The observation that WEB 2170 and CV3988, 2 structurally
      unrelated PAF receptor antagonists, prevented the motility of HUVECs induced by
      TPO suggests a role of PAF as secondary mediator. Moreover, kinetic analysis of
      TPO-induced tyrosine phosphorylation of STAT demonstrated that STAT5B activation
      temporally correlated with the synthesis of PAF. PAF, in turn, induced a rapid
      tyrosine phosphorylation of STAT5B and PAF receptor blockade, by WEB 2170,
      preventing both TPO- and PAF-mediated STAT5B activation. The in vivo angiogenic
      effect of TPO, studied in a mouse model of Matrigel implantation, demonstrated
      that TPO induced a dose-dependent angiogenic response that required the presence
      of heparin. Moreover, the in vivo angiogenic effect of TPO was inhibited by the
      PAF receptor antagonist WEB 2170 but not by the anti-basic fibroblast growth
      factor neutralizing antibody. These results indicate that the effects of TPO are
      not restricted to cells of hematopoietic lineages, because TPO is able to
      activate endothelial cells and to induce an angiogenic response in which the
      recruitment of endothelial cells is mediated by the synthesis of PAF. Moreover,
      biochemical analysis supports the hypothesis that STAT5B may be involved in the
      signaling pathway leading to PAF-dependent angiogenesis.

PMID- 10205149
TI  - Natural androgens inhibit male atherosclerosis: a study in castrated, cholesterol
      fed rabbits.
AB  - The effect of natural androgens on serum lipids and atherosclerosis is
      controversial. We therefore studied this important issue prospectively in an
      animal model of atherosclerosis. Eighty male rabbits were randomized to bilateral
      castration, and 20 animals were sham operated. The castrated rabbits were
      randomized to 500 mg oral dehydroepiandrosterone (DHEA) daily, 80 mg oral
      testosterone undecanoate (TU) daily, or 25-mg intramuscular injection of
      testosterone enanthate (TE) twice weekly, whereas the fourth castrated group
      (placebo) and the sham-operated rabbits did not receive any hormones. All animals
      were fed a cholesterol-rich diet during the 30-week treatment period. Average
      serum lipids and atherogenic lipoproteins were higher in the placebo group than
      in the other groups (ANOVA, P<0.0001). Aortic atherosclerosis, as evaluated by
      the cholesterol content (nmol/mg protein), was also highest in the placebo group
      (308+/-39) and lowest in the TE group (61+/-12), but was intermediate in the DHEA
      (155+/-30), TU (191+/-43), and sham operation (162+/-29) groups (ANOVA,
      P<0.0001). ANCOVA indicated that the androgen effect on aortic atherosclerosis
      was only in part explained by the changes in lipoproteins. Aortic estrogen
      receptor contents were significantly lower in the androgen-treated groups than in
      the control groups, whereas there was no difference in aortic androgen receptor
      contents between groups. Natural androgens inhibit aortic atherosclerosis in
      castrated male rabbits only partly through a lipid-mediated effect.

PMID- 10205148
TI  - Modulation of Ras/Raf/extracellular signal-regulated kinase pathway by reactive
      oxygen species is involved in cyclic strain-induced early growth response-1 gene
      expression in endothelial cells.
AB  - Endothelial cells (ECs) exposed to cyclic strain induce gene expression. To
      elucidate the signaling mechanisms involved, we studied the effects of cyclic
      strain on ECs by using early growth response-1 (Egr-1) as a target gene. Cyclic
      strain induced a transient increase of Egr-1 mRNA levels that resulted in an
      increase of binding of nuclear proteins to the Egr-1 binding sequences in the
      platelet-derived growth factor-A promoter region. ECs subjected to strain
      enhanced Egr-1 transcription as revealed by promoter activities. Catalase
      pretreatment inhibited this induction. ECs, transfected with a dominant positive
      mutant of Ras (RasL61), increased Egr-1 promoter activities. In contrast,
      transfection with a dominant negative mutant of Ras (RasN17) attenuated this
      strain inducibility. ECs transfected with a dominant negative mutant of Raf-1
      (Raf301) or the catalytically inactive mutant of extracellular signal-regulated
      kinase (ERK)-2 (mERK2) diminished strain-induced promoter activities. However,
      little effect on strain inducibility was observed in ECs transfected with a
      dominant negative mutant of Rac (RacN17) or a catalytically inactive mutant of
      JNK (JNK[K-R]). Consistently, strain-induced Egr-1 expression was inhibited after
      ECs were treated with a specific inhibitor (PD98059) to mitogen-activated protein
      kinase kinase. Moreover, strain to ECs induced mitogen-activated protein
      kinase/ERK activity. The activation of the ERK pathway was further substantiated
      by an increase of strain-induced transcriptional activity of Elk1, an ERK
      substrate. This strain-induced ERK activity was attenuated after ECs were treated
      with N-acetylcysteine or catalase. Consequently, this Egr-1 gene induction was
      abolished after ECs were treated with N-acetylcysteine or catalase. Deletion
      analyses of the promoter region (-698 bp) indicated that cyclic strain and H2O2
      shared a common serum response element. Our data clearly indicate that cyclic
      strain-induced Egr-1 expression is mediated mainly via the Ras/Raf-1/ERK pathway
      and that strain-induced reactive oxygen species can modulate Egr-1 expression at
      least partially via this signaling pathway.

PMID- 10205150
TI  - cdc25A is necessary but not sufficient for optimal c-myc-induced apoptosis and
      cell proliferation of vascular smooth muscle cells.
AB  - Increasing evidence indicates that the control of cell proliferation and
      apoptosis are linked. The c-myc proto-oncogene is induced early after cell-cycle
      entry in vascular smooth muscle cells (VSMCs) in vitro and after arterial injury
      and regulates both cell proliferation and apoptosis. Although both proliferation
      and apoptosis are likely to be mediated via transcriptional activation of target
      genes, few c-myc targets have been identified. Therefore, the recent
      identification that cdc25A, a cell-cycle phosphatase involved in G1 progression,
      is transcriptionally activated by c-myc and regulates c-myc-induced apoptosis has
      suggested that cdc25A may be the principal mediator of c-myc in VSMCs. We
      examined cdc25A regulation of c-myc-induced proliferation and apoptosis by
      expressing cdc25A or antisense cdc25A in primary rat VSMCs or in VSMCs expressing
      deregulated c-myc or adenovirus E1A. Ectopic c-myc increased cdc25A expression,
      but cdc25A was still responsive to serum components, which indicated that c-myc
      alone is not the main determinant of cdc25A expression. Antisense cdc25A
      inhibited c-myc-induced proliferation and apoptosis; however, drug and metabolic
      blocks indicated that this effect was limited to G1. Ectopic cdc25A augmented the
      proproliferative and proapoptotic action of c-myc but did not increase cell
      proliferation or apoptosis in the absence of ectopic c-myc. In contrast, E1A/E2F
      induced apoptosis was independent of cdc25A. We conclude that cdc25A expression
      modulates the ability of c-myc to induce apoptosis in G1. However, cdc25A alone
      does not induce apoptosis and cannot substitute for c-myc in VSMCs. Additional
      targets of c-myc are therefore involved in apoptosis of both G1 and post-G1
      VSMCs.

PMID- 10205151
TI  - Activation of p38 mitogen-activated protein kinase by oxidized LDL in vascular
      smooth muscle cells: mediation via pertussis toxin-sensitive G proteins and
      association with oxidized LDL-induced cytotoxicity.
AB  - Oxidized low-density lipoproteins (oxLDL) have been shown to play a crucial role
      in atherosclerosis, but the underlying molecular mechanisms have not been fully
      understood. The present study showed that oxLDL strongly evoked phosphorylation
      and activation of p38 mitogen-activated protein kinase (MAPK) in rat vascular
      smooth muscle cells (VSMCs) in concentration- and time-dependent manners,
      reaching the maximal activation at 100 microg/mL within 5 minutes. The results
      from immunofluorescence staining also revealed that p38 MAPK was activated by
      oxLDL in 5 minutes, and the activated p38 MAPK was translocated from cytoplasm to
      nucleus of VSMCs in 15 minutes. Activation of p38 MAPK by oxLDL was apparently
      not mediated by their classical scavenger receptors and was not affected by
      tyrosine kinase inhibitors. However, activation of p38 MAPK was effectively
      blocked by pretreatment with pertussis toxin and was significantly reduced by
      phospholipase C inhibitor U-73122. OxLDL also inhibited forskolin-stimulated cAMP
      accumulation and increased inositol phosphate formation. More interestingly,
      inhibition of p38 MAPK by its specific inhibitor SB203580 significantly blocked
      oxLDL-induced cytotoxicity (increased leakage of cytoplasmic lactate
      dehydrogenase to the culture medium, reduced [3H]thymidine incorporation, and
      attenuated mitochondrial metabolism of tetrazolium salt, (3-(4, 5-dimethylthiazol
      2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-s ulfophenyl)- 2H-tetrazolium), MTS) in
      VSMCs, and pretreatment with pertussis toxin also inhibited oxLDL-induced
      cytotoxicity. Taken together, our data clearly demonstrated that oxLDL
      effectively activated p38 MAPK in VSMCs, which was likely mediated via pertussis
      toxin-sensitive G proteins, and the p38 activation was functionally associated
      with oxLDL-induced cytotoxicity in VSMCs.

PMID- 10205152
TI  - Endogenous endothelial nitric oxide synthase-derived nitric oxide is a
      physiological regulator of myocardial oxygen consumption.
AB  - Our objective was to determine the precise role of endothelial nitric oxide
      synthase (eNOS) as a modulator of cardiac O2 consumption and to further examine
      the role of nitric oxide (NO) in the control of mitochondrial respiration. Left
      ventricle O2 consumption in mice with defects in the expression of eNOS [eNOS (-/
      )] and inducible NOS [iNOS (-/-)] was measured with a Clark-type O2 electrode.
      The rate of decreases in O2 concentration was expressed as a percentage of the
      baseline. Baseline O2 consumption was not significantly different between groups
      of mice. Bradykinin (10(-4) mol/L) induced significant decreases in O2
      consumption in tissues taken from iNOS (-/-) (-28+/-4%), wild-type eNOS (+/+) (
      22+/-4%), and heterozygous eNOS(+/-) (-22+/-5%) but not homozygous eNOS (-/-) (
      3+/-4%) mice. Responses to bradykinin in iNOS (-/-) and both wild-type and
      heterozygous eNOS mice were attenuated after NOS blockade with N-nitro-L-arginine
      methyl ester (L-NAME) (-2+/-5%, -3+/-2%, and -6+/-5%, respectively, P<0.05). In
      contrast, S-nitroso-N-acetyl-penicillamine (SNAP, 10(-4) mol/L), which releases
      NO spontaneously, induced decreases in myocardial O2 consumption in all groups of
      mice, and such responses were not affected by L-NAME. In addition, pretreatment
      with bacterial endotoxin elicited a reduction in basal O2 consumption in tissues
      taken from normal but not iNOS (-/-)-deficient mice. Our results indicate that
      the pivotal role of eNOS in the control of myocardial O2 consumption and
      modulation of mitochondrial respiration by NO may have an important role in
      pathological conditions such as endotoxemia in which the production of NO is
      altered.

PMID- 10205153
TI  - Opioid-induced second window of cardioprotection: potential role of mitochondrial
      KATP channels.
AB  - Opioids have been previously shown to confer short-term cardioprotection against
      a prolonged ischemic insult. Therefore, the present study was designed to
      determine whether opioids can induce a delayed or "second window" of
      cardioprotection and to assess the potential involvement of the mitochondrial
      KATP channel. All rats were subjected to 30 minutes of ischemia and 2 hours of
      reperfusion (I/R). Control animals, injected with saline 24 hours before I/R,
      elicited an infarct size/area at risk (IS/AAR) of 62.9+/-3.4. TAN-67, a delta1
      opioid receptor agonist, was administered 10 or 30 mg/kg IP 12, 24, 48, or 72
      hours before I/R. TAN-67 (10 mg/kg) 12- or 24-hour pretreatment did not
      significantly reduce IS/AAR (62.1+/-6.3 and 43.3+/-7.3, respectively). Similarly,
      12-hour pretreatment with TAN-67 (30 mg/kg) did not reduce IS/AAR (60.0+/-5.6);
      however, 24-hour pretreatment significantly reduced IS/AAR (34.5+/-5.9). Forty
      eight-hour pretreatment with TAN-67 maximally reduced IS/AAR (29.2+/-7.0), and
      opioid-induced cardioprotection was lost after 72-hour pretreatment (61.7+/-3.8).
      TAN-67-induced cardioprotection could be abolished by pretreatment with the
      selective delta1-opioid receptor antagonist 7-benzylidenenaltrexone, BNTX,
      administered either 30 minutes before TAN-67 given 48 hours before I/R or 10
      minutes before I/R in rats previously treated for 48 hours with TAN-67 (59.6+/
      3.1 and 58.7+/-3.5, respectively). The involvement of the KATP channel was
      investigated with 2 inhibitors: glibenclamide, a nonselective KATP channel
      inhibitor, and 5-hydroxydecanoic acid, selective for the mitochondrial KATP
      channel in rabbits. Glibenclamide, administered 30 minutes before I/R in 48-hour
      TAN-67-pretreated rats, completely abolished cardioprotection (60. 4+/-3.2).
      Similarly, 5-hydroxydecanoic acid, administered 5 minutes before I/R in rats
      pretreated 48 hours previously with TAN-67, completely abolished cardioprotection
      (57.8+/-2.5). These results suggest that delta1-opioid receptor stimulation, 24
      to 48 hours before an ischemic insult, produces a delayed cardioprotective effect
      that is possibly the result of mitochondrial KATP channel activation.

PMID- 10205155
TI  - Plasticity in the dynamics of myocardial contraction: Ca2+, crossbridge kinetics,
      or molecular cooperation.

PMID- 10205154
TI  - Regulation of smooth muscle alpha-actin expression in vivo is dependent on CArG
      elements within the 5' and first intron promoter regions.
AB  - The aims of the present studies were to define sufficient promoter sequences
      required to drive endogenous expression of smooth muscle (SM) alpha-actin and to
      determine whether regulation of SM alpha-actin expression in vivo is dependent on
      CArG (CC(A/T)6GG) cis elements. Promoter deletions and site directed mutagenesis
      techniques were used to study gene regulation in transgenic mice as well as in
      smooth muscle cell (SMC) cultures. Results demonstrated that a Lac Z transgene
      that contained 547 bp of the 5' rat SM alpha-actin promoter was sufficient to
      drive embryonic expression of SM alpha-actin in the heart and in skeletal muscle
      but not in SMCs. Transient transfections into SMC cultures demonstrated that the
      conserved CArG element in the first intron had significant positive activity, and
      gel shift analyses demonstrated that the intronic CArG bound serum response
      factor. A transgene construct from -2600 through the first intron (p2600Int/Lac
      Z) was expressed in embryos and adults in a pattern that closely mimicked
      endogenous SM alpha-actin expression. Expression in adult mice was completely
      restricted to SMCs and was detected in esophagus, stomach, intestine, lung, and
      nearly all blood vessels, including coronary, mesenteric, and renal vascular
      beds. Mutation of CArG B completely inhibited expression in all cell types,
      whereas mutation of the intronic CArG selectively abolished expression in SMCs,
      which suggests that it may act as an SMC-specific enhancer-like element. Taken
      together, these results provide the first in vivo evidence for the importance of
      multiple CArG cis elements in the regulation of SM alpha-actin expression.

PMID- 10205156
TI  - The crystal structure of a novel bacterial adenylyltransferase reveals half of
      sites reactivity.
AB  - Phosphopantetheine adenylyltransferase (PPAT) is an essential enzyme in bacteria
      that catalyses a rate-limiting step in coenzyme A (CoA) biosynthesis, by
      transferring an adenylyl group from ATP to 4'-phosphopantetheine, yielding
      dephospho-CoA (dPCoA). Each phosphopantetheine adenylyltransferase (PPAT) subunit
      displays a dinucleotide-binding fold that is structurally similar to that in
      class I aminoacyl-tRNA synthetases. Superposition of bound adenylyl moieties from
      dPCoA in PPAT and ATP in aminoacyl-tRNA synthetases suggests nucleophilic attack
      by the 4'-phosphopantetheine on the alpha-phosphate of ATP. The proposed
      catalytic mechanism implicates transition state stabilization by PPAT without
      involving functional groups of the enzyme in a chemical sense in the reaction.
      The crystal structure of the enzyme from Escherichia coli in complex with dPCoA
      shows that binding at one site causes a vice-like movement of active site
      residues lining the active site surface. The mode of enzyme product formation is
      highly concerted, with only one trimer of the PPAT hexamer showing evidence of
      dPCoA binding. The homologous active site attachment of ATP and the structural
      distribution of predicted sequence-binding motifs in PPAT classify the enzyme as
      belonging to the nucleotidyltransferase superfamily.

PMID- 10205157
TI  - Crystal structure of baculovirus P35: role of a novel reactive site loop in
      apoptotic caspase inhibition.
AB  - The aspartate-specific caspases are critical protease effectors of programmed
      cell death and consequently represent important targets for apoptotic
      intervention. Baculovirus P35 is a potent substrate inhibitor of metazoan
      caspases, a property that accounts for its unique effectiveness in preventing
      apoptosis in phylogenetically diverse organisms. Here we report the 2.2 A
      resolution crystal structure of P35, the first structure of a protein inhibitor
      of the death caspases. The P35 monomer possesses a solvent-exposed loop that
      projects from the protein's main beta-sheet core and positions the requisite
      aspartate cleavage site at the loop's apex. Distortion or destabilization of this
      reactive site loop by site-directed mutagenesis converted P35 to an efficient
      substrate which, unlike wild-type P35, failed to interact stably with the target
      caspase or block protease activity. Thus, cleavage alone is insufficient for
      caspase inhibition. These data are consistent with a new model wherein the P35
      reactive site loop participates in a unique multi-step mechanism in which the
      spatial orientation of the loop with respect to the P35 core determines post
      cleavage association and stoichiometric inhibition of target caspases.

PMID- 10205158
TI  - Presence of a pre-apoptotic complex of pro-caspase-3, Hsp60 and Hsp10 in the
      mitochondrial fraction of jurkat cells.
AB  - Activation of pro-caspase-3 is a central event in the execution phase of
      apoptosis and appears to serve as the convergence point of different apoptotic
      signaling pathways. Recently, mitochondria were found to play a central role in
      apoptosis through release of cytochrome c and activation of caspases. Moreover, a
      sub-population of pro-caspase-3 has been found to be localized to this organelle.
      In the present study, we demonstrate that pro-caspase-3 is present in the
      mitochondrial fraction of Jurkat T cells in a complex with the chaperone proteins
      Hsp60 and Hsp10. Induction of apoptosis with staurosporine led to the activation
      of mitochondrial pro-caspase-3 and its dissociation from the Hsps which were
      released from mitochondria. The release of Hsps occurred simultaneously with the
      release of other mitochondrial intermembrane space proteins including cytochrome
      c and adenylate kinase, prior to a loss of mitochondrial transmembrane potential.
      In in vitro systems, recombinant Hsp60 and Hsp10 accelerated the activation of
      pro-caspase-3 by cytochrome c and dATP in an ATP-dependent manner, consistent
      with their function as chaperones. This finding suggests that the release of
      mitochondrial Hsps may also accelerate caspase activation in the cytoplasm of
      intact cells.

PMID- 10205159
TI  - Hsp60 accelerates the maturation of pro-caspase-3 by upstream activator proteases
      during apoptosis.
AB  - The activation of caspases represents a critical step in the pathways leading to
      the biochemical and morphological changes that underlie apoptosis. Multiple
      pathways leading to caspase activation appear to exist and vary depending on the
      death-inducing stimulus. We demonstrate that the activation of caspase-3, in
      Jurkat cells stimulated to undergo apoptosis by a Fas-independent pathway, is
      catalyzed by caspase-6. Caspase-6 was found to co-purify with caspase-3 as part
      of a multiprotein activation complex from extracts of camptothecin-treated Jurkat
      cells. A biochemical analysis of the protein constituents of the activation
      complex showed that Hsp60 was also present. Furthermore, an interaction between
      Hsp60 and caspase-3 could be demonstrated by co-immunoprecipitation experiments
      using HeLa as well as Jurkat cell extracts. Using a reconstituted in vitro
      system, Hsp60 was able to substantially accelerate the maturation of procaspase-3
      by different upstream activator caspases and this effect was dependent on ATP
      hydrolysis. We propose that the ATP-dependent 'foldase' activity of Hsp60
      improves the vulnerability of pro-caspase-3 to proteolytic maturation by upstream
      caspases and that this represents an important regulatory event in apoptotic cell
      death.

PMID- 10205160
TI  - Flagellar protein localization mediated by a calcium-myristoyl/palmitoyl switch
      mechanism.
AB  - The mechanisms by which proteins are targeted to flagella and cilia are poorly
      understood. We set out to determine the basis for the specific localization of a
      24 kDa flagellar calcium-binding protein (FCaBP) expressed in all life cycle
      stages of Trypanosoma cruzi. Through the study of trypanosome transfectants
      expressing various FCaBP deletion mutants, we found that the N-terminal 24 amino
      acids of the protein are necessary and sufficient for flagellar localization.
      Subsequent experiments revealed that FCaBP is myristoylated and palmitoylated
      and, in fact, is one of very few proteins in the cell possessing these acyl
      modifications. Both fatty acids are required for flagellar localization,
      suggesting that FCaBP localization may be mediated through association with the
      flagellar plasma membrane. Indeed, FCaBP associates with the flagellar membrane
      in a calcium-dependent manner, reminiscent of the recoverin family of calcium
      myristoyl switch proteins. Thus, FCaBP is a novel member of the calcium-acyl
      switch protein family and is the only member described to date that requires two
      fatty acid modifications for specific membrane association. Its unique
      localization mechanism is the first described for any flagellar protein. The
      existence of such a protein in this protozoan suggests that acylation and calcium
      switch mechanisms for regulated membrane association are conserved among
      eukaryotes.

PMID- 10205161
TI  - AUX1 regulates root gravitropism in Arabidopsis by facilitating auxin uptake
      within root apical tissues.
AB  - Plants employ a specialized transport system composed of separate influx and
      efflux carriers to mobilize the plant hormone auxin between its site(s) of
      synthesis and action. Mutations within the permease-like AUX1 protein
      significantly reduce the rate of carrier-mediated auxin uptake within Arabidopsis
      roots, conferring an agravitropic phenotype. We are able to bypass the defect
      within auxin uptake and restore the gravitropic root phenotype of aux1 by growing
      mutant seedlings in the presence of the membrane-permeable synthetic auxin, 1
      naphthaleneacetic acid. We illustrate that AUX1 expression overlaps that
      previously described for the auxin efflux carrier, AtPIN2, using transgenic lines
      expressing an AUX1 promoter::uidA (GUS) gene. Finally, we demonstrate that AUX1
      regulates gravitropic curvature by acting in unison with the auxin efflux carrier
      to co-ordinate the localized redistribution of auxin within the Arabidopsis root
      apex. Our results provide the first example of a developmental role for the auxin
      influx carrier within higher plants and supply new insight into the molecular
      basis of gravitropic signalling.

PMID- 10205162
TI  - Cytosolic ATPases, p97 and NSF, are sufficient to mediate rapid membrane fusion.
AB  - Much recent work has focussed on the role of membrane-bound components in fusion.
      We show here that p97 and NSF are sufficient to mediate rapid membrane fusion.
      Fractionation of cytosol revealed that p97 and its co-factor, p47, constitutes
      the major fusion activity. This was confirmed by depleting p97 from the cytosol,
      which resulted in an 80% decrease in fusion. Using purified protein, p97 or NSF
      was found to be sufficient to mediate rapid fusion in an ATP-dependent manner. A
      regulatory role was observed for their corresponding co-factors, p47 and alpha
      SNAP. When present at a molar ratio half of that of the ATPase, both co-factors
      increased fusion activity significantly. Intriguingly, at this ratio the ATPase
      activity of the complex measured in solution was at its lowest, suggesting that
      the co-factor stabilizes the ATP state. The fusion event involved mixing of both
      leaflets of the opposing membranes and contents of liposomes. We conclude from
      these data that p97, NSF and perhaps other related ATPases catalyse rapid and
      complete fusion between lipid bilayers on opposing membranes. This highlights a
      new role for p97 and NSF and prompts a re-evaluation of current fusion models.

PMID- 10205163
TI  - Sequence determinants directing conversion of cysteine to formylglycine in
      eukaryotic sulfatases.
AB  - Sulfatases carry at their catalytic site a unique post-translational
      modification, an alpha-formylglycine residue that is essential for enzyme
      activity. Formylglycine is generated by oxidation of a conserved cysteine or, in
      some prokaryotic sulfatases, serine residue. In eukaryotes, this oxidation occurs
      in the endoplasmic reticulum during or shortly after import of the nascent
      sulfatase polypeptide. The modification of arylsulfatase A was studied in vitro
      and was found to be directed by a short linear sequence, CTPSR, starting with the
      cysteine to be modified. Mutational analyses showed that the cysteine, proline
      and arginine are the key residues within this motif, whereas formylglycine
      formation tolerated the individual, but not the simultaneous substitution of the
      threonine or serine. The CTPSR motif was transferred to a heterologous protein
      leading to low-efficient formylglycine formation. The efficiency reached control
      values when seven additional residues (AALLTGR) directly following the CTPSR
      motif in arylsulfatase A were present. Mutating up to four residues
      simultaneously within this heptamer sequence inhibited the modification only
      moderately. AALLTGR may, therefore, have an auxiliary function in presenting the
      core motif to the modifying enzyme. Within the two motifs, the key residues are
      fully, and other residues are highly conserved among all known members of the
      sulfatase family.

PMID- 10205164
TI  - Chemoattractant-mediated transient activation and membrane localization of
      Akt/PKB is required for efficient chemotaxis to cAMP in Dictyostelium.
AB  - Chemotaxis-competent cells respond to a variety of ligands by activating second
      messenger pathways leading to changes in the actin/myosin cytoskeleton and
      directed cell movement. We demonstrate that Dictyostelium Akt/PKB, a homologue of
      mammalian Akt/PKB, is very rapidly and transiently activated by the
      chemoattractant cAMP. This activation takes place through G protein-coupled
      chemoattractant receptors via a pathway that requires homologues of mammalian
      p110 phosphoinositide-3 kinase. pkbA null cells exhibit aggregation-stage defects
      that include aberrant chemotaxis, a failure to polarize properly in a
      chemoattractant gradient and aggregation at low densities. Mechanistically, we
      demonstrate that the PH domain of Akt/PKB fused to GFP transiently translocates
      to the plasma membrane in response to cAMP with kinetics similar to those of
      Akt/PKB kinase activation and is localized to the leading edge of chemotaxing
      cells in vivo. Our results indicate Akt/PKB is part of the regulatory network
      required for sensing and responding to the chemoattractant gradient that mediates
      chemotaxis and aggregation.

PMID- 10205165
TI  - The p16(INK4a) tumour suppressor protein inhibits alphavbeta3 integrin-mediated
      cell spreading on vitronectin by blocking PKC-dependent localization of
      alphavbeta3 to focal contacts.
AB  - Expression of full-length p16(INK4a) blocks alphavbeta3 integrin-dependent cell
      spreading on vitronectin but not collagen IV. Similarly, G1-associated cell cycle
      kinases (CDK) inhibitory (CKI) synthetic peptides derived from p16(INK4a),
      p18(INK4c) and p21(Cip1/Waf1), which can be delivered directly into cells from
      the tissue culture medium, do not affect non-alphavbeta3-dependent spreading on
      collagen IV, laminin and fibronectin at concentrations that inhibit cell cycle
      progression in late G1. The alphavbeta3 heterodimer remains intact after CKI
      peptide treatment but is immediately dissociated from the focal adhesion
      contacts. Treatment with phorbol 12-myristate 13-acetate (PMA) allows alphavbeta3
      to locate to the focal adhesion contacts and the cells to spread on vitronectin
      in the presence of CKI peptides. The cdk6 protein is found to suppress p16(INK4a)
      mediated inhibition of spreading and is also shown to localize to the ruffling
      edge of spreading cells, indicating a function for cdk6 in controlling matrix
      dependent cell spreading. These results demonstrate a novel G1 CDK-associated
      integrin regulatory pathway that acts upstream of alphavbeta3-dependent
      activation of PKC as well as a novel function for the p16(INK4a) tumour
      suppressor protein in regulating matrix-dependent cell migration.

PMID- 10205166
TI  - A casein kinase I motif present in the cytoplasmic domain of members of the
      tumour necrosis factor ligand family is implicated in 'reverse signalling'.
AB  - We have identified a putative signalling feature of the cytoplasmic domains of
      the tumour necrosis factor (TNF) family members based on available amino acid
      sequence data. A casein kinase I (CKI) consensus sequence is conserved in the
      cytoplasmic domain of six of 15 members of the type II integral membrane TNF
      ligand family. We examined the phosphorylation state of transmembrane tumour
      necrosis factor-alpha (mTNF) with [32P]orthophosphate labelling and in vitro
      kinase assays, in lipopolysaccharide-stimulated RAW264.7 cells. A dimeric form of
      the type I soluble TNF receptor (sTNFR) was found to dephosphorylate mTNF. This
      effect could be prevented by treatment with phosphatase inhibitors. Recombinant
      CKI was able to phosphorylate mTNF that had been dephosphorylated by sTNFR
      ligation in vivo, and this was less effective if phosphatase inhibitors had been
      used to prevent mTNF dephosphorylation. A mutated form of mTNF, lacking the CKI
      recognition site, cannot be phosphorylated by the enzyme. Binding of sTNFR to
      mTNF induced an increase in intracellular calcium levels in RAW264.7 cells,
      implying the presence of an associated signalling pathway. We predict that this
      CKI motif is phosphorylated in other TNF ligand members, and that it represents a
      new insight into the mechanism of 'reverse signalling' in this cytokine family.

PMID- 10205167
TI  - Fetal liver development requires a paracrine action of oncostatin M through the
      gp130 signal transducer.
AB  - Fetal liver, the major site of hematopoiesis during embryonic development,
      acquires additional various metabolic functions near birth. Although liver
      development has been characterized biologically as consisting of several distinct
      steps, the molecular events accompanying this process are just beginning to be
      characterized. In this study, we have established a novel culture system of fetal
      murine hepatocytes and investigated factors required for development of
      hepatocytes. We found that oncostatin M (OSM), an interleukin-6 family cytokine,
      in combination with glucocorticoid, induced maturation of hepatocytes as
      evidenced by morphological changes that closely resemble more differentiated
      hepatocytes, expression of hepatic differentiation markers and intracellular
      glycogen accumulation. Consistent with these in vitro observations, livers from
      mice deficient for gp130, an OSM receptor subunit, display defects in maturation
      of hepatocytes. Interestingly, OSM is expressed in CD45(+) hematopoietic cells in
      the developing liver, whereas the OSM receptor is expressed predominantly in
      hepatocytes. These results suggest a paracrine mechanism of hepatogenesis; blood
      cells, transiently expanding in the fetal liver, produce OSM to promote
      development of hepatocytes in vivo.

PMID- 10205168
TI  - Serine and tyrosine phosphorylations cooperate in Raf-1, but not B-Raf
      activation.
AB  - The Raf family of serine/threonine protein kinases couple growth factor receptor
      stimulation to mitogen activated protein kinase activation, but their own
      regulation is poorly understood. Using phospho-specific antisera, we show that
      activated Raf-1 is phosphorylated on S338 and Y341. Expression of Raf-1 with
      oncogenic Ras gives predominantly S338 phosphorylation, whereas activated Src
      gives predominantly Y341 phosphorylation. Phosphorylation at both sites is
      maximal only when both oncogenic Ras and activated Src are present. Raf-1 that
      cannot interact with Ras-GTP is not phosphorylated, showing that phosphorylation
      is Ras dependent, presumably occurring at the plasma membrane. Mutations which
      prevent phosphorylation at either site block Raf-1 activation and maximal
      activity is seen only when both are phosphorylated. Mutations at S339 or Y340 do
      not block Raf-1 activation. While B-Raf lacks a tyrosine phosphorylation site
      equivalent to Y341 of Raf-1, S445 of B-Raf is equivalent to S338 of Raf-1.
      Phosphorylation of S445 is constitutive and is not stimulated by oncogenic Ras.
      However, S445 phosphorylation still contributes to B-Raf activation by elevating
      basal and consequently Ras-stimulated activity. Thus, there are considerable
      differences between the activation of the Raf proteins; Ras-GTP mediates two
      phosphorylation events required for Raf-1 activation but does not regulate such
      events for B-Raf.

PMID- 10205170
TI  - Surface densities of ephrin-B1 determine EphB1-coupled activation of cell
      attachment through alphavbeta3 and alpha5beta1 integrins.
AB  - Receptors of the Eph family and their ligands (ephrins) mediate developmental
      vascular assembly and direct axonal guidance. Migrating cell processes identify
      appropriate targets within migratory fields based on topographically displayed
      ephrin gradients. Here, EphB1 regulated cell attachment by discriminating the
      density at which ephrin-B1 was displayed on a reconstituted surface. EphB1-ephrin
      B1 engagement did not promote cell attachment through mechanical tethering, but
      did activate integrin-mediated attachment. In endothelial cells, attachment to
      RGD peptides or fibrinogen was mediated through alphavbeta3 integrin. EphB1
      transfection conferred ephrin-B1-responsive activation of alpha5beta1 integrin
      mediated cell attachment in human embryonic kidney cells. Activation-competent
      but signaling-defective EphB1 point mutants failed to stimulate ephrin-B1
      dependent attachment. These findings lead us to propose that EphB1 functions as a
      'ligand density sensor' to signal integrin-mediated cell-matrix attachment.

PMID- 10205169
TI  - Elevated expression of activated forms of Neu/ErbB-2 and ErbB-3 are involved in
      the induction of mammary tumors in transgenic mice: implications for human breast
      cancer.
AB  - To assess the importance of Neu activation during mammary tumorigenesis, altered
      receptors harboring in-frame deletions within the extracellular domain were
      expressed in transgenic mice. Females from several independent lines develop
      multiple mammary tumors that frequently metastasize to the lung. Tumor
      progression in these strains was associated with elevated levels of tyrosine
      phosphorylated Neu and ErbB-3. Consistent with these observations, a survey of
      primary human breast tumors revealed frequent co-expression of both erbB-2 and
      erbB-3 transcripts. The ability of altered Neu receptors to induce mammary
      tumorigenesis in transgenic mice prompted us to examine whether similar mutations
      occurred in ErbB-2 during human breast cancer progression. Interestingly, an
      alternatively spliced form of erbB-2, closely resembling spontaneous activated
      forms of neu, was detected in human breast tumors. The ErbB-2 receptor encoded by
      this novel transcript harbors an in-frame deletion of 16 amino acids in the
      extracellular domain and can transform Rat-1 fibroblasts. Together, these
      observations argue that co-expression of ErbB-2 and ErbB-3 may play a critical
      role in the induction of human breast tumors, and raise the possibility that
      activating mutations in the ErbB-2 receptor may also contribute to this process.

PMID- 10205171
TI  - Maintenance of G2 arrest in the Xenopus oocyte: a role for 14-3-3-mediated
      inhibition of Cdc25 nuclear import.
AB  - Cdc2-cyclin B1 in the G2-arrested Xenopus oocyte is held inactive by
      phosphorylation of Cdc2 at two negative regulatory sites, Thr14 and Tyr15. Upon
      treatment with progesterone, these sites are dephosphorylated by the dual
      specificity phosphatase, Cdc25, leading to Cdc2-cyclin B1 activation. Whereas
      maintenance of the G2 arrest depends upon preventing Cdc25-induced Cdc2
      dephosphorylation, the mechanisms responsible for keeping Cdc25 in check in these
      cells have not yet been described. Here we report that Cdc25 in the G2-arrested
      oocyte is bound to 14-3-3 proteins and that progesterone treatment abrogates this
      binding. We demonstrate that Cdc25, apparently statically localized in the
      cytoplasm, is actually capable of shuttling in and out of the oocyte nucleus.
      Binding of 14-3-3 protein markedly reduces the nuclear import rate of Cdc25,
      allowing nuclear export mediated by a nuclear export sequence present in the N
      terminus of Cdc25 to predominate. If 14-3-3 binding to Cdc25 is prevented while
      nuclear export is inhibited, the coordinate nuclear accumulation of Cdc25 and
      Cdc2-cyclin B1 facilitates their mutual activation, thereby promoting oocyte
      maturation.

PMID- 10205172
TI  - The disappearance of cyclin B at the end of mitosis is regulated spatially in
      Drosophila cells.
AB  - We have followed the behaviour of a cyclin B-green fluorescent protein (GFP)
      fusion protein in living Drosophila embryos in order to study how the
      localization and destruction of cyclin B is regulated in space and time. We show
      that the fusion protein accumulates at centrosomes in interphase, in the nucleus
      in prophase, on the mitotic spindle in prometaphase and on the microtubules that
      overlap in the middle of the spindle in metaphase. In cellularized embryos,
      toward the end of metaphase, the spindle-associated cyclin B-GFP disappears from
      the spindle in a wave that starts at the spindle poles and spreads to the spindle
      equator; when the cyclin B-GFP on the spindle is almost undetectable, the
      chromosomes enter anaphase, and any remaining cytoplasmic cyclin B-GFP then
      disappears over the next few minutes. The endogenous cyclin B protein appears to
      behave in a similar manner. These findings suggest that the inactivation of
      cyclin B is regulated spatially in Drosophila cells. We show that the anaphase
      promoting complex/cyclosome (APC/C) specifically interacts with microtubules in
      embryo extracts, but it is not confined to the spindle in mitosis, suggesting
      that the spatially regulated disappearance of cyclin B may reflect the spatially
      regulated activation of the APC/C.

PMID- 10205173
TI  - Hes1 and Hes5 as notch effectors in mammalian neuronal differentiation.
AB  - While the transmembrane protein Notch plays an important role in various aspects
      of development, and diseases including tumors and neurological disorders, the
      intracellular pathway of mammalian Notch remains very elusive. To understand the
      intracellular pathway of mammalian Notch, the role of the bHLH genes Hes1 and
      Hes5 (mammalian hairy and Enhancer-of-split homologues) was examined by
      retrovirally misexpressing the constitutively active form of Notch (caNotch) in
      neural precursor cells prepared from wild-type, Hes1-null, Hes5-null and Hes1
      Hes5 double-null mouse embryos. We found that caNotch, which induced the
      endogenous Hes1 and Hes5 expression, inhibited neuronal differentiation in the
      wild-type, Hes1-null and Hes5-null background, but not in the Hes1-Hes5 double
      null background. These results demonstrate that Hes1 and Hes5 are essential Notch
      effectors in regulation of mammalian neuronal differentiation.

PMID- 10205174
TI  - The C-terminal domain of armadillo binds to hypophosphorylated teashirt to
      modulate wingless signalling in Drosophila.
AB  - Wnt signalling is a key pathway for tissue patterning during animal development.
      In Drosophila, the Wnt protein Wingless acts to stabilize Armadillo inside cells
      where it binds to at least two DNA-binding factors which regulate specific target
      genes. One Armadillo-binding protein in Drosophila is the zinc finger protein
      Teashirt. Here we show that Wingless signalling promotes the phosphorylation and
      the nuclear accumulation of Teashirt. This process requires the binding of
      Teashirt to the C-terminal end of Armadillo. Finally, we present evidence that
      the serine/threonine kinase Shaggy is associated with Teashirt in a complex. We
      discuss these results with respect to current models of Armadillo/beta-catenin
      action for the transmission of the Wingless/Wnt pathway.

PMID- 10205175
TI  - A 3'-flanking NF-kappaB site mediates developmental silencing of the human zeta
      globin gene.
AB  - The central developmental event in the human (h)alpha-globin gene cluster is
      selective silencing of the zeta-globin gene as erythropoiesis shifts from
      primitive erythroblasts in the embryonic yolk sac to definitive erythroblasts in
      the fetal liver. Previous studies have demonstrated that full developmental
      silencing of the hzeta-globin gene in transgenic mice requires the proximal 2.1
      kb of its 3'-flanking region. In the current report, we localize this silencing
      activity to a 108 bp segment located 1.2 kb 3' to the zeta-globin gene.
      Protein(s) in nuclear extracts from cell lines representing the fetal/adult
      erythroid stage bind specifically to an NF-kappaB motif located at this site. In
      contrast, this binding activity is lacking in the nuclear extract of an embryonic
      stage erythroid line expressing zeta-globin. This complex is quantitatively
      recognized by antisera to the NF-kappaB p50 and to a lesser extent to p65
      subunits. A two-base substitution that disrupts NF-kappaB site protein binding in
      vitro also results in the loss of the developmental silencing activity in vivo.
      The data suggest that NF-kappaB complex formation is a crucial component of hzeta
      globin gene silencing. This finding expands the roles of this widely distributed
      transcriptional complex to include negative regulation in mammalian development.

PMID- 10205177
TI  - Regional specialization in human nuclei: visualization of discrete sites of
      transcription by RNA polymerase III.
AB  - Mammalian nuclei contain three different RNA polymerases defined by their
      characteristic locations and drug sensitivities; polymerase I is found in
      nucleoli, and polymerases II and III in the nucleoplasm. As nascent transcripts
      made by polymerases I and II are concentrated in discrete sites, the locations of
      those made by polymerase III were investigated. HeLa cells were lysed with
      saponin in an improved 'physiological' buffer that preserves transcriptional
      activity and nuclear ultrastructure; then, engaged polymerases were allowed to
      extend nascent transcripts in Br-UTP, before the resulting Br-RNA was
      immunolabelled indirectly with fluorochromes or gold particles. Biochemical
      analysis showed that approximately 10 000 transcripts were being made by
      polymerase III at the moment of lysis, while confocal and electron microscopy
      showed that these transcripts were concentrated in only approximately 2000 sites
      (diameter approximately 40 nm). Therefore, each site contains approximately five
      active polymerases. These sites contain specific subunits of polymerase III, but
      not the hyperphosphorylated form of the largest subunit of polymerase II. The
      results indicate that the active forms of all three nuclear polymerases are
      concentrated in their own dedicated transcription sites or 'factories',
      suggesting that different regions of the nucleus specialize in the transcription
      of different types of gene.

PMID- 10205176
TI  - Role of the essential yeast protein PSU1 in p6anscriptional enhancement by the
      ligand-dependent activation function AF-2 of nuclear receptors.
AB  - Nuclear receptors (NRs) can function as ligandinducible transregulators in both
      mammalian and yeast cells, indicating that important features of transcriptional
      control have been conserved throughout evolution. We report here the isolation
      and characterization of an essential yeast protein of unknown function, PSU1,
      which exhibits properties expected for a co-activator/mediator of the ligand
      dependent activation function AF-2 present in the ligand-binding domain (LBD,
      region E) of NRs. PSU1 interacts in a ligand-dependent manner with the LBD of
      several NRs, including retinoic acid (RARalpha), retinoid X (RXRalpha), thyroid
      hormone (TRalpha), vitamin D3 (VDR) and oestrogen (ERalpha) receptors.
      Importantly, both in yeast and in vitro, these interactions require the integrity
      of the AF-2 activating domain. When tethered to a heterologous DNA-binding
      domain, PSU1 can activate transcription on its own. By using yeast reporter cells
      that express PSU1 conditionally, we show that PSU1 is required for
      transactivation by the AF-2 of ERalpha. Taken together these data suggest that in
      yeast, PSU1 is involved in ligand-dependent transactivation by NRs. Sequence
      analysis revealed that in addition to a highly conserved motif found in a family
      of MutT-related proteins, PSU1 contains several alpha-helical leucine-rich motifs
      sharing the consensus sequence LLxPhiL (x, any amino acid; Phi, hydrophobic amino
      acid) in regions that elicit either transactivation or NR-binding activity.

PMID- 10205178
TI  - Continuous and widespread roles for the Swi-Snf complex in transcription.
AB  - Chromatin presents a significant obstacle to transcription, but two means of
      overcoming its repressive effects, histone acetylation and the activities of the
      Swi-Snf complex, have been proposed. Histone acetylation and Swi-Snf activity
      have been shown to be crucial for transcriptional induction and to facilitate
      binding of transcription factors to DNA. By regulating the activity of the Swi
      Snf complex in vivo, we found that active transcription requires continuous Swi
      Snf function, demonstrating a role for this complex beyond the induction of
      transcription. Despite the presumably generalized packaging of genes into
      chromatin, previous studies have indicated that the transcriptional requirements
      for the histone acetyltransferase, Gcn5, and the Swi-Snf complex are limited to a
      handful of genes. However, inactivating Swi-Snf function in cells also lacking
      GCN5 revealed defects in transcription of several genes previously thought to be
      SWI-SNF- and GCN5-independent. These findings suggest that chromatin remodeling
      plays a widespread role in gene expression and that these two chromatin
      remodeling activities perform independent and overlapping functions during
      transcriptional activation.

PMID- 10205179
TI  - Trypanosoma brucei variant surface glycoprotein regulation involves coupled
      activation/inactivation and chromatin remodeling of expression sites.
AB  - Trypanosoma brucei is an extracellular protozoan parasite that cycles between
      mammalian hosts and the tsetse vector. In bloodstream-form trypanosomes, only one
      variant surface glycoprotein gene (VSG) expression site (ES) is active at any
      time. Transcriptional switching between ESs results in antigenic variation. No
      VSG is transcribed in the insect procyclic stage. We have used bacteriophage T7
      RNA polymerase (T7RNAP) to study the transcriptional accessibility of ES
      chromatin in vivo. We show that T7RNAP-mediated transcription from chromosomally
      integrated T7 promoters is repressed along the entire length of the ES in the
      procyclic form, but not in the bloodstream form, suggesting that the accessible
      chromatin of inactive bloodstream-form ESs is remodeled upon differentiation to
      yield a structure that is no longer permissive for T7RNAP-mediated transcription.
      In the bloodstream form, replacing the active ES promoter with a T7 promoter,
      which is incapable of sustaining high-level transcription of the entire ES,
      prompts an ES switch. These data suggest two distinct mechanisms for ES
      regulation: a chromatin-mediated developmental silencing of the ES in the
      procyclic form and a rapid coupled mechanism for ES activation and inactivation
      in the bloodstream form.

PMID- 10205180
TI  - Influenza A virus NS1 protein targets poly(A)-binding protein II of the cellular
      3'-end processing machinery.
AB  - Influenza A virus NS1 protein (NS1A protein) via its effector domain targets the
      poly(A)-binding protein II (PABII) of the cellular 3'-end processing machinery.
      In vitro the NS1A protein binds the PABII protein, and in vivo causes PABII
      protein molecules to relocalize from nuclear speckles to a uniform distribution
      throughout the nucleoplasm. In vitro the NS1A protein inhibits the ability of
      PABII to stimulate the processive synthesis of long poly(A) tails catalyzed by
      poly(A) polymerase (PAP). Such inhibition also occurs in vivo in influenza virus
      infected cells, where the NS1A protein via its effector domain causes the nuclear
      accumulation of cellular pre-mRNAs which contain short ( approximately 12
      nucleotide) poly(A) tails. Consequently, although the NS1A protein also binds the
      30 kDa subunit of the cleavage and polyadenylation specificity factor (CPSF), 3'
      cleavage of some cellular pre-mRNAs still occurs in virus-infected cells,
      followed by the PAP-catalyzed addition of short poly(A) tails. Subsequent
      elongation of these short poly(A) tails is blocked because the NS1A protein
      inhibits PABII function. Nuclear-cytoplasmic shuttling of PABII, an activity
      implicating this protein in the nuclear export of cellular mRNAs, is also
      inhibited by the NS1A protein. In vitro assays suggest that the 30 kDa CPSF and
      PABII proteins bind to non-overlapping regions of the NS1A protein effector
      domain and indicate that these two 3' processing proteins also directly bind to
      each other.

PMID- 10205181
TI  - Dynamics and efficiency in vivo of UGA-directed selenocysteine insertion at the
      ribosome.
AB  - The kinetics and efficiency of decoding of the UGA of a bacterial selenoprotein
      mRNA with selenocysteine has been studied in vivo. A gst-lacZ fusion, with the
      fdhF SECIS element ligated between the two fusion partners, gave an efficiency of
      read-through of 4-5%; overproduction of the selenocysteine insertion machinery
      increased it to 7-10%. This low efficiency is caused by termination at the UGA
      and not by translational barriers at the SECIS. When the selenocysteine UGA codon
      was replaced by UCA, and tRNASec with anticodon UGA was allowed to compete with
      seryl-tRNASer1 for this codon, selenocysteine was found in 7% of the protein
      produced. When a non-cognate SelB-tRNASec complex competed with EF-Tu for a sense
      codon, no effects were seen, whereas a non-cognate SelB-tRNASec competing with EF
      Tu-mediated Su7-tRNA nonsense suppression of UGA interfered strongly with
      suppression. The induction kinetics of beta-galactosidase synthesis from fdhF'
      'lacZ gene fusions in the absence or presence of SelB and/or the SECIS element,
      showed that there was a translational pause in the fusion containing the SECIS
      when SelB was present. The results show that decoding of UGA is an inefficient
      process and that using the third dimension of the mRNA to accommodate an
      additional amino acid is accompanied by considerable quantitative and kinetic
      costs.

PMID- 10205182
TI  - Cytoplasmic polyadenylation elements mediate masking and unmasking of cyclin B1
      mRNA.
AB  - During oocyte maturation, cyclin B1 mRNA is translationally activated by
      cytoplasmic polyadenylation. This process is dependent on cytoplasmic
      polyadenylation elements (CPEs) in the 3' untranslated region (UTR) of the mRNA.
      To determine whether a titratable factor might be involved in the initial
      translational repression (masking) of this mRNA, high levels of cyclin B1 3' UTR
      were injected into oocytes. While this treatment had no effect on the poly(A)
      tail length of endogenous cyclin B1 mRNA, it induced cyclin B1 synthesis. A
      mutational analysis revealed that the most efficient unmasking element in the
      cyclin 3' UTR was the CPE. However, other U-rich sequences that resemble the CPE
      in structure, but which do not bind the CPE-binding polyadenylation factor CPEB,
      failed to induce unmasking. When fused to the chloramphenical acetyl transferase
      (CAT) coding region, the cyclin B1 3' UTR inhibited CAT translation in injected
      oocytes. In addition, a synthetic 3' UTR containing multiple copies of the CPE
      also inhibited translation, and did so in a dose-dependent manner. Furthermore,
      efficient CPE-mediated masking required cap-dependent translation. During the
      normal course of progesterone-induced maturation, cytoplasmic polyadenylation was
      necessary for mRNA unmasking. A model to explain how cyclin B1 mRNA masking and
      unmasking could be regulated by the CPE is presented.

PMID- 10205183
TI  - Binding of SeqA protein to DNA requires interaction between two or more complexes
      bound to separate hemimethylated GATC sequences.
AB  - The SeqA protein binds to the post-replicative forms of the origins of
      replication of the Escherichia coli chromosome (oriC) and the P1 plasmid (P1oriR)
      at hemimethylated GATC adenine methylation sites. It appears to regulate
      replication by preventing premature reinitiation. However, SeqA binding is not
      exclusive to replication origins: different fragments with hemimethylated GATC
      sites can bind SeqA in vitro when certain rules apply. Most notably, more than
      one such site must be present on a bound fragment. The protein appears to
      recognize individual hemimethylated sites, but must undergo an obligate
      cooperative interaction with a nearby bound protein for stable binding. SeqA
      contacts both DNA strands in a discrete patch at each hemimethylated GATC
      sequence. All four GATC bases are contacted and are essential for binding.
      Although the recognized sequence is symmetrical, the footprint on the methylated
      strand is always broader, suggesting that the bound protein is positioned
      asymmetrically with its orientation dictated by the position of the unique methyl
      group. Studies of alternative spacings and relative orientations of adjacent
      sites suggest that each site may be recognized by a symmetrical dimer with an
      induced asymmetry in one of the subunits similar to that seen with certain type
      II restriction endonucleases.

PMID- 10205184
TI  - Colorectal neoplasia in acromegaly.

PMID- 10205186
TI  - Double reflux: double trouble.

PMID- 10205185
TI  - Divergency of leptin response in intestinal inflammation.

PMID- 10205187
TI  - Is mycophenolate mofetil a new alternative in the treatment of inflammatory bowel
      disease?

PMID- 10205189
TI  - PBC and the gut: the villi atrophy, the plot thickens.

PMID- 10205188
TI  - Beans means lectins.

PMID- 10205190
TI  - The adenomatous polyposis coli tumour suppressor gene regulates c-MYC
      transcription in colon cancer cells.

PMID- 10205191
TI  - Review: substantial coffee consumption was associated with a lower risk of
      colorectal cancer in the general population.

PMID- 10205192
TI  - Toxic bile acids in gastro-oesophageal reflux disease: influence of gastric
      acidity.
AB  - BACKGROUND: Bile acid toxicity has been shown in the gastric, colonic, and
      hepatic tissues; the effect on oesophageal mucosa is less well known. AIMS: To
      determine the spectrum of bile acids refluxing in patients with gastro
      oesophageal reflux disease and its relation to oesophageal pH using a new
      technique of combined oesophageal aspiration and pH monitoring. METHODS: Ten
      asymptomatic subjects and 30 patients with symptoms of gastro-oesophageal reflux
      disease (minimal mucosal injury, erosive oesophagitis (grade 2 or 3 Savary
      Miller), Barrett's oesophagus/stricture; n=10 in each group) underwent 15 hour
      continuous oesophageal aspiration with simultaneous pH monitoring. Bile acid
      assay of the oesophageal samples was performed using modified high performance
      liquid chromatography. RESULTS: The peak bile acid concentration and DeMeester
      acid scores were significantly higher in the patients with oesophagitis (median
      bile acid concentration 124 micromol/l; acid score 20.2) and Barrett's
      oesophagus/stricture (181 micromol/l; 43. 3) than patients with minimal injury
      (14 micromol/l; 12.5) or controls (0 micromol/l; 11.1). The predominant bile
      acids detected were cholic, taurocholic, and glycocholic acids but there was a
      significantly greater proportion of secondary bile acids, deoxycholic and
      taurodeoxycholic acids, in patients with erosive oesophagitis and Barrett's
      oesophagus/stricture. Although bile acid reflux episodes occurred at variable pH,
      a temporal relation existed between reflux of taurine conjugates and oesophageal
      acid exposure (r=0.58, p=0.009). CONCLUSION: Toxic secondary bile acid fractions
      have been detected in patients with extensive mucosal damage. Mixed reflux is
      more harmful than acid reflux alone with possible toxic synergism existing
      between the taurine conjugates and acid.

PMID- 10205193
TI  - Cholinergic blockade inhibits gastro-oesophageal reflux and transient lower
      oesophageal sphincter relaxation through a central mechanism.
AB  - BACKGROUND: Atropine, an anticholinergic agent with central and peripheral
      actions, reduces gastro-oesophageal reflux (GOR) in normal subjects and patients
      with gastro-oesophageal reflux disease (GORD) by inhibiting the frequency of
      transient lower oesophageal sphincter relaxation (TLOSR). AIMS: To compare the
      effect of methscopolamine bromide (MSB), a peripherally acting anticholinergic
      agent, with atropine on the rate and mechanism of GOR in patients with GORD.
      METHODS: Oesophageal motility and pH were recorded for 120 minutes in 10 patients
      with GORD who were studied on three separate occasions. For the first two
      recording periods, either atropine (15 microg/kg bolus, 4 microg/kg/h infusion)
      or saline were infused intravenously. MSB (5 mg orally, four times daily) was
      given for three days prior to the third recording period. RESULTS: Atropine
      significantly reduced basal LOS pressure (12.6 (0.17) mm Hg to 7.9 (0.17) mm Hg),
      and the number of TLOSR (8.1 (0.56) to 2.8 (0. 55)) and reflux episodes (7.0
      (0.63) to 2.0 (0.43)) (p<0.005 for all comparisons). MSB reduced basal LOS
      pressure (12.6 (0.17) to 8.7 (0. 15) mm Hg, p<0.005), but had no effect on the
      frequency of TLOSR (8. 1 (0.56) to 7.5 (0.59)) and reflux episodes (7.0 (0.63) to
      4.9 (0. 60)) (p>0.05). CONCLUSION: In contrast to atropine, MSB has no effect on
      the rate of TLOSR or GOR in patients with GORD. Atropine induced inhibition of
      TLOSR and GOR is most likely mediated through a central cholinergic blockade.

PMID- 10205194
TI  - The effects of glutamine on intestinal epithelial cell proliferation in
      parenterally fed rats.
AB  - BACKGROUND: Several papers have indicated that glutamine is a preferred fuel for
      the enterocyte and that it can increase intestinal epithelial cell proliferation.
      AIMS: To investigate the effects of glutamine on intestinal epithelial cell
      proliferation in the parenterally fed rat. METHODS: Five groups of six rats were
      fed parenterally; a group of orally fed rats was also studied. Crypt cell
      proliferation was studied after six days using native mitoses in microdissected
      crypts and bromodeoxyuridine labelling. RESULTS: No effect of treatment was seen
      on intestinal weight; however, the weights of the small intestine, caecum, and
      colon were all significantly heavier in the orally fed group than in the total
      parenteral nutrition groups (p<0.001). There was no effect of any of the
      glutamine treatments on mitotic activity in the small intestine. In the colon
      there was a small increase in native mitoses with glutamine (p=0.03). There was
      also an indication of increased proliferative activity in the first fifth of the
      small intestine and colon with glutamine. Little effect of glutamine on
      bromodeoxyuridine labelling in either site was observed, but there was a small
      but significant reduction in growth fraction of the colon of the glutamine
      treated group. The labelling distribution curve from sections and the mitotic
      distribution curve obtained from crypt squashes showed a good correlation.
      CONCLUSION: Glutamine has a small, but significant effect on mitotic activity but
      only in the colon. Modest effects on the distribution of labelled cells were also
      seen.

PMID- 10205195
TI  - Vagotomy inhibits the jejunal fluid secretion activated by luminal ileal
      Escherichia coli STa in the rat in vivo.
AB  - BACKGROUND: Escherichia coli heat stable enterotoxin (STa) is a major cause of
      secretory diarrhoea in humans. AIMS: To assess the effects of instilling STa into
      the ileum on remote fluid secretion in the jejunum and colon in rats in vivo by a
      gravimetric technique. METHODS AND RESULTS: Ileal STa (55 ng/ml) stimulated fluid
      secretion in both ileal and jejunal loops but not in the colon. The fluid
      secretion induced by ileal STa was inhibited by L-NAME (Nomega-nitro-L-arginine
      methyl ester, 40 mg/kg intraperitoneally) but not by D-NAME (Nomega-nitro-D
      arginine methyl ester). Ileal carbachol (183 mg/ml) instilled into the lumen
      stimulated ileal secretion but not jejunal secretion, and was unaffected by L
      NAME. Capsaicin (10 microM), instilled luminally with STa in the ileum, blocked
      both the ileal and jejunal fluid secretion. Acute bilateral vagotomy prevented
      luminal ileal STa from inducing jejunal fluid secretion but not from activating
      ileal fluid secretion. CONCLUSION: Ileal E coli STa stimulates remote secretion
      in the rat jejunum but not in the colon, probably by a nitrinergic, vagal reflex
      mediated by C fibres. This neural pathway will amplify the action of the toxin in
      its generation of secretory diarrhoea.

PMID- 10205196
TI  - Characterisation of penicillin G uptake in human small intestinal brush border
      membrane vesicles.
AB  - BACKGROUND: Many beta lactams are well absorbed by the small intestine, although
      the reasons for this are poorly understood. AIMS: To characterise the uptake of
      penicillin G into human small intestinal brush border membrane vesicles (BBMV)
      and to compare the uptake characteristics to those of rabbit BBMV. METHODS AND
      RESULTS: Uptake of penicillin G was studied in human BBMV. Penicillin G was
      actively transported into the lumen of BBMV via an H+ dependent, Na+ independent
      uptake system. The carrier mediated process was saturable and adhered to
      Michaelis-Menten kinetics (Vmax 52 nmol penicillin G per mg protein per 30
      seconds, Km 13.9 mM). These results are similar to those previously reported in
      rabbit BBMV. CONCLUSIONS: It is suggested that penicillin G can be used as a
      model molecule for peptide and beta lactam transport studies as it is cheap and
      readily available in isotopically labelled form. Furthermore, rabbit BBMV may be
      used as an acceptable substitute for human BBMV for the study of penicillin
      transport.

PMID- 10205197
TI  - Randomised trial of mycophenolate mofetil versus azathioprine for treatment of
      chronic active Crohn's disease.
AB  - BACKGROUND: Crohn's disease is a chronic inflammatory disease of the alimentary
      tract. Azathioprine is an effective agent in the management of chronic active
      Crohn's disease leading to long term remission of disease activity. Such
      treatment leads to limited efficacy or side effects in a small subset of
      patients. AIMS: To compare efficacy and side effects of treatment with
      azathioprine plus corticosteroids versus mycophenolate mofetil (MMF) plus
      corticosteroids in patients with chronic active Crohn's disease. METHODS: Seventy
      patients with chronic active Crohn's disease (Crohn's disease activity index
      (CDAI) greater than 150) were randomised for treatment with
      azathioprine/cortisone or MMF/cortisone. Corticosteroid dosage was tapered
      according to a standard protocol. Disease activity was monitored by clinical
      scores after one, two, three, and six months. RESULTS: Treatment of patients with
      moderately active (CDAI 150-300) Crohn's disease with MMF/cortisone led to a
      significant reduction in clinical activity scores comparable to treatment with
      azathioprine/cortisone. Treatment of patients with highly active Crohn's disease
      (CDAI greater than 300) with MMF/cortisone caused significant suppression of
      clinical activity earlier than azathioprine/cortisone treatment. Treatment with
      MMF/cortisone was associated with few adverse effects. CONCLUSION: Treatment of
      chronic active Crohn's disease with MMF plus cortisone appears to be effective
      and well tolerated and should be considered in patients allergic to azathioprine
      or in whom azathioprine has failed.

PMID- 10205198
TI  - Enhanced production of monocyte chemotactic protein 3 in inflammatory bowel
      disease mucosa.
AB  - BACKGROUND: The beta chemokine monocyte chemotactic protein 3 (MCP-3) has
      chemoattractant and activating capabilities in monocytes, lymphocytes,
      eosinophils, and basophils. AIMS: To investigate MCP-3 expression in inflammatory
      conditions of the human intestinal mucosa. PATIENTS: Forty five colon biopsy
      specimens from 18 patients with inflammatory bowel disease (IBD; 16 specimens
      from inflamed and 10 from non-inflamed areas) and 19 control patients were
      examined. METHODS: Immunohistochemical staining and reverse transcription
      polymerase chain reaction (RT-PCR) were used for MCP-3 detection in tissue
      sections. Intestinal epithelial cell lines (HT-29, Caco-2, T-84) were stimulated
      with interleukin (IL) 1beta, IL-6, and tumour necrosis factor alpha (TNF-alpha)
      and examined for MCP-3 protein and mRNA expression using immunocytochemistry and
      RT-PCR, respectively. RESULTS: In tissue sections, MCP-3 protein was detected
      predominantly in epithelial cells, both in patients with IBD and in controls. MCP
      3 staining was particularly pronounced at sites of active mucosal inflammation.
      The intensity of MCP-3 staining was positively correlated with the extent of
      epithelial destruction. In intestinal epithelial cell lines, MCP-3 mRNA was
      expressed, whereas MCP-3 protein was not consistently detected. CONCLUSIONS: Our
      data show that MCP-3 protein is present in normal and inflamed intestinal tissue.
      MCP-3 production is substantially enhanced in areas of active inflammation,
      suggesting an immunoregulatory role of MCP-3 in intestinal inflammation.

PMID- 10205200
TI  - Mast cells are an important cellular source of tumour necrosis factor alpha in
      human intestinal tissue.
AB  - BACKGROUND: Several inflammatory disorders of the intestine are characterised by
      enhanced expression of tumour necrosis factor alpha (TNF-alpha). Monocytes and
      macrophages have been suggested as a major cellular source of TNF-alpha in human
      gut, whereas mast cells, although known to be capable of producing TNF-alpha,
      have been poorly examined in this respect. AIMS: To investigate whether human
      intestinal mast cells can produce TNF-alpha, and which factors regulate TNF-alpha
      production in these cells. METHODS: Mast cells were isolated from surgery tissue
      specimens of patients undergoing bowel resection because of cancer.
      Immunohistochemical studies were performed in biopsy specimens derived from 13
      patients (two healthy controls, four with Crohn's disease, four with ulcerative
      colitis, three others). TNF-alpha mRNA and protein expression were studied in
      vitro by polymerase chain reaction, RNAse protection assay, western blot, and
      enzyme linked immunosorbent assay in isolated purified human intestinal mast
      cells stimulated by IgE receptor crosslinking, intestinal bacteria, and
      lipopolysaccharide. Cellular localisation of TNF-alpha was examined by
      immunohistochemistry. RESULTS: TNF-alpha mRNA and protein were expressed
      constitutively in isolated human intestinal mast cells. Expression of TNF-alpha
      mRNA and release of TNF-alpha protein were substantially enhanced by IgE receptor
      crosslinking and by coculture of mast cells with intestinal bacteria;
      lipopolysaccharide had only marginal effects. Immunohistochemical studies
      revealed that approximately 60% of the lamina propria cells with immunoreactivity
      for TNF-alpha were mast cells. CONCLUSIONS: The data show that mast cells are an
      important source of TNF-alpha in the human intestinal mucosa.

PMID- 10205199
TI  - Trefoil peptide TFF2 (spasmolytic polypeptide) potently accelerates healing and
      reduces inflammation in a rat model of colitis.
AB  - BACKGROUND: The trefoil peptides are major secretory products of mucus cells of
      the gastrointestinal tract and show increased expression after inflammatory or
      ulcerative damage. Recombinant human TFF2 (spasmolytic polypeptide) has been
      shown to be cytoprotective, and enhances repair in models of gastric injury.
      AIMS: To test the healing effects of recombinant human (h)TFF2 in a rat model of
      chronic colitis. METHODS: Colitis was induced by intracolonic administration of
      dinitrobenzene sulphonic acid in ethanol. Mucosal repair was quantified
      macroscopically, microscopically by image analysis of tissue histology, and by
      measuring myeloperoxidase activity. RESULTS: Initial validation studies showed
      that maximal injury and inflammation occurred at the end of the first week after
      colitis induction (active phase), and that spontaneous healing was complete by
      eight weeks. Once daily intrarectal application of hTFF2 (2.5 mg/kg;
      approximately 0.5 mg/rat) for five days after maximal damage had been sustained,
      reduced both microscopic and macroscopic injury by 80% and inflammatory index by
      50% compared with vehicle controls. In addition, endogenous concentrations of rat
      TFF2 and TFF3 (intestinal trefoil factor) were increased in the active phase of
      colitis and were reduced to basal levels by hTFF2 treatment. CONCLUSIONS: This
      study has shown that hTFF2 enhances the rate of colonic epithelial repair, and
      reduces local inflammation in a rat model of colitis, and suggests that luminal
      application of trefoil peptides may have therapeutic potential in the treatment
      of inflammatory bowel disease.

PMID- 10205201
TI  - Bovine colostrum is a health food supplement which prevents NSAID induced gut
      damage.
AB  - BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are effective for
      arthritis but cause gastrointestinal injury. Bovine colostrum is a rich source of
      growth factors and is marketed as a health food supplement. AIMS: To examine
      whether spray dried, defatted colostrum or milk preparations could reduce
      gastrointestinal injury caused by indomethacin. METHODS: Effects of test
      solutions, administered orally, were examined using an indomethacin restraint rat
      model of gastric damage and an indomethacin mouse model of small intestinal
      injury. Effects on migration of the human colonic carcinoma cell line HT-29 and
      rat small intestinal cell line RIE-1 were assessed using a wounded monolayer
      assay system (used as an in vitro model of wound repair) and effects on
      proliferation determined using [3H]thymidine incorporation. RESULTS: Pretreatment
      with 0.5 or 1 ml colostral preparation reduced gastric injury by 30% and 60%
      respectively in rats. A milk preparation was much less efficacious. Recombinant
      transforming growth factor beta added at a dose similar to that found in the
      colostrum preparation (12.5 ng/rat), reduced injury by about 60%. Addition of
      colostrum to drinking water (10% vol/vol) prevented villus shortening in the
      mouse model of small intestinal injury. Addition of milk preparation was
      ineffective. Colostrum increased proliferation and cell migration of RIE-1 and HT
      29 cells. These effects were mainly due to constituents of the colostrum with
      molecular weights greater than 30 kDa. CONCLUSIONS: Bovine colostrum could
      provide a novel, inexpensive approach for the prevention and treatment of the
      injurious effects of NSAIDs on the gut and may also be of value for the treatment
      of other ulcerative conditions of the bowel.

PMID- 10205202
TI  - Acquired interferon gamma responsiveness during Caco-2 cell differentiation:
      effects on iNOS gene expression.
AB  - BACKGROUND: Impairment of intestinal barrier function occurs under a variety of
      inflammatory conditions and is mediated at least in part by interferon gamma (IFN
      gamma) induced nitric oxide (NO) production. Previous in vivo studies have shown
      that systemic lipopolysaccharide treatment caused an induction of the rat
      inducible nitric oxide synthase (iNOS) mRNA primarily in villus cells, rather
      than in undifferentiated crypt cells. AIMS: To examine iNOS induction by IFN
      gamma in vitro as a function of enterocyte differentiation. METHODS: Preconfluent
      and postconfluent Caco-2 cells were treated with IFN-gamma in the presence or
      absence of various inhibitors. Northern analyses were performed to assess the
      magnitude of iNOS mRNA induction. IFN-gamma receptor mRNA and protein levels were
      determined. RESULTS: iNOS mRNA induction by IFN-gamma occurred at two hours and
      was not blocked by cycloheximide, indicating that it is an immediate early
      response. iNOS induction and nitrite/nitrate increases were inhibited by
      dexamethasone and pyrrolidine dithiocarbamate, supporting an important role for
      the NF-kappaB transcription factor in this process. The stimulated iNOS induction
      was seen almost exclusively under conditions of cellular differentiation-that is,
      in postconfluent Caco-2 cells. This increased IFN-gamma responsiveness seen in
      postconfluent Caco-2 cells correlated with an increased expression of IFN-gamma
      receptor, whereas T84 and HT-29 cells did not show any significant alterations in
      either iNOS induction or IFN-gamma receptor levels as a function of postconfluent
      growth. CONCLUSIONS: With regard to iNOS mRNA induction, IFN-gamma responsiveness
      is acquired during Caco-2 cell differentiation, perhaps related to an increase in
      the numbers of IFN-gamma receptors.

PMID- 10205204
TI  - Prolonged large bowel transit increases serum deoxycholic acid: a risk factor for
      octreotide induced gallstones.
AB  - BACKGROUND: Treatment of acromegaly with octreotide increases the proportion of
      deoxycholic acid in, and the cholesterol saturation of, bile and induces the
      formation of gallstones. Prolongation of intestinal transit has been proposed as
      the mechanism for the increase in the proportion of deoxycholic acid in bile.
      AIMS: To study the effects of octreotide on intestinal transit in acromegalic
      patients during octreotide treatment, and to examine the relation between
      intestinal transit and bile acid composition in fasting serum. METHODS: Mouth to
      caecum and large bowel transit times, and the proportion of deoxycholic acid in
      fasting serum were measured in non-acromegalic controls, acromegalic patients
      untreated with octreotide, acromegalics on long term octreotide, and patients
      with simple constipation. Intestinal transit and the proportion of deoxycholic
      acid were compared in acromegalic patients before and during octreotide. RESULTS:
      Acromegalics untreated with octreotide had longer mouth to caecum and large bowel
      transit times than controls. Intestinal transit was further prolonged by chronic
      octreotide treatment. There were significant linear relations between large bowel
      transit time and the proportion of deoxycholic acid in the total, conjugated, and
      unconjugated fractions of fasting serum. CONCLUSIONS: These data support the
      hypothesis that, by prolonging large bowel transit, octreotide increases the
      proportion of deoxycholic acid in fasting serum (and, by implication, in bile)
      and thereby the risk of gallstone formation.

PMID- 10205203
TI  - Notable postnatal alterations in the myenteric plexus of normal human bowel.
AB  - BACKGROUND: Nitric oxide is the most important transmitter in non-adrenergic non
      cholinergic nerves in the human gastrointestinal tract. Impaired nitrergic
      innervation has been described in Hirschsprung's disease, hypertrophic pyloric
      stenosis, and intestinal neuronal dysplasia (IND). Recent findings indicate that
      hyperganglionosis, one of the major criteria of IND, is age dependent. However,
      information is scanty regarding the neurone density in normal human bowel in the
      paediatric age group. AIMS: To determine neurone density, morphology, and nitric
      oxide synthase distribution of the normal myenteric plexus at different ages
      during infancy and childhood. METHODS: Specimens were obtained from small bowel
      and colon in 20 children, aged one day to 15 years, at postmortem examination.
      Whole mount preparations were made of the myenteric plexus, which were
      subsequently stained using NADPH diaphorase histochemistry (identical to nitric
      oxide synthase) and cuprolinic blue (a general neuronal marker). The morphology
      of the myenteric plexus was described and the neurone density estimated. RESULTS:
      The myenteric plexus meshwork becomes less dense during the first years of life.
      The density of ganglion cells in the myenteric plexus decreases significantly
      with age during the first three to four years of life. The NADPH diaphorase
      positive (nitrergic) subpopulation represents about 34% of all neurones in the
      myenteric plexus. CONCLUSIONS: The notable decrease in neurone density in the
      myenteric plexus during the first years of life indicates that development is
      still an ongoing process in the postnatal enteric nervous system. Applied to the
      clinical situation, this implies that interpretation of enteric nervous system
      pathology is dependent on the age of the patient.

PMID- 10205205
TI  - Selective stimulation of colonic transit by the benzofuran 5HT4 agonist,
      prucalopride, in healthy humans.
AB  - BACKGROUND: Prucalopride (R093877) is a selective and specific 5HT4 agonist, the
      first of a new chemical class of benzofurans, with gastrointestinal prokinetic
      activities in vitro. AIMS: To evaluate the effects of prucalopride on
      gastrointestinal and colonic transit. METHODS: A validated scintigraphic
      technique was used to measure gastrointestinal and colonic transit over 48 hours
      in 50 healthy volunteers. For seven days, each subject received a daily dose of
      0. 5, 1, 2, or 4 mg prucalopride, or placebo in a double blind, randomised
      fashion. The transit test was performed over the last 48 hours. RESULTS: There
      were significant accelerations of overall colonic transit at 4, 8, 24, and 48
      hours (p<0.05) and proximal colonic emptying t1/2 (p<0.05). The 0.5, 2, and 4 mg
      doses of prucalopride were almost equally effective and accelerated colonic
      transit compared with placebo. Prucalopride did not significantly alter gastric
      emptying (p>0.5) or small bowel transit (overall p=0. 12). The medication
      appeared to be well tolerated during the seven day treatment of healthy subjects.
      CONCLUSION: Prucalopride accelerates colonic transit, partly by stimulating
      proximal colonic emptying, but does not alter gastric or small bowel transit in
      healthy human subjects. Prucalopride deserves further study in patients with
      constipation.

PMID- 10205206
TI  - Perception of and adaptation to rectal isobaric distension in patients with
      faecal incontinence.
AB  - BACKGROUND: Perception of, and adaptation of the rectum to, distension probably
      play an important role in the maintenance of continence, but perception studies
      in faecal incontinence provide controversial conclusions possibly related to
      methodological biases. In order to better understand perception disorders, the
      aim of this study was to analyse anorectal adaptation to rectal isobaric
      distension in subjects with incontinence. PATIENTS/METHODS: Between June 95 and
      December 97, 97 consecutive patients (nine men and 88 women, mean (SEM) age 55
      (1) years) suffering from incontinence were evaluated and compared with 15
      healthy volunteers (four men and 11 women, mean age 48 (3) years). The patients
      were classified into three groups according to their perception status to rectal
      isobaric distensions (impaired, 22; normal, 61; enhanced, 14). Anal and rectal
      adaptations to increasing rectal pressure were analysed using a model of rectal
      isobaric distension. RESULTS: The four groups did not differ with respect to age,
      parity, or sex ratio. Magnitude of incontinence, prevalence of pelvic disorders,
      and sphincter defects were similar in the incontinent groups. When compared with
      healthy controls, anal pressure and rectal adaptation to distension were
      decreased in incontinent patients. When compared with incontinent patients with
      normal perception, patients with enhanced perception experienced similar rectal
      adaptation but had reduced anal pressure. In contrast, patients with impaired
      perception showed considerably decreased rectal adaptation but had similar anal
      pressure. CONCLUSION: Abnormal sensations during rectal distension are observed
      in one third of subjects suffering from incontinence. These abnormalities may
      reflect hyperreactivity or neuropathological damage of the rectal wall.

PMID- 10205207
TI  - Accuracy of screening for gastric cancer using serum pepsinogen concentrations.
AB  - BACKGROUND/AIMS: The characteristics of pepsinogen screening for gastric cancer
      were investigated to establish a suitable cut off point for identifying gastric
      cancer, using endoscopic diagnosis as the yardstick. SUBJECTS/METHODS: Serum
      pepsinogen concentrations were measured in 5113 subjects who were also screened
      for gastric cancer by endoscopy. The cut off point for pepsinogen was determined
      using receiver operator characteristics curves. RESULTS: The most suitable cut
      off point was a pepsinogen I concentration of less than 70 ng/ml and a ratio of
      pepsinogen I to pepsinogen II of less than 3. 0. Using this cut off point, the
      sensitivity and specificity of pepsinogen screening for gastric cancer were 84.6%
      and 73.5% respectively. All cases of gastric cancer in patients with severe
      atrophic gastritis were detected. However, two of four cases of gastric cancer in
      patients with mild atrophic gastritis were overlooked. In subjects with mild
      atrophic gastritis, when gastric cancer arises within the fundic gland region,
      the size of the lesion determines whether it is possible to detect cancer by
      serum pepsinogen screening. CONCLUSION: Pepsinogen screening has many advantages,
      including its suitability for combination with other screening methods because it
      is simple and inexpensive.

PMID- 10205208
TI  - Cost comparison of predictive genetic testing versus conventional clinical
      screening for familial adenomatous polyposis.
AB  - BACKGROUND: Mutations of the APC gene cause familial adenomatous polyposis (FAP),
      a hereditary colorectal cancer predisposition syndrome. AIMS: To conduct a cost
      comparison analysis of predictive genetic testing versus conventional clinical
      screening for individuals at risk of inheriting FAP, using the perspective of a
      third party payer. METHODS: All direct health care costs for both screening
      strategies were measured according to time and motion, and the expected costs
      evaluated using a decision analysis model. RESULTS: The baseline analysis
      predicted that screening a prototype FAP family would cost $4975/ pound3109 by
      molecular testing and $8031/ pound5019 by clinical screening strategy, when
      family members were monitored with the same frequency of clinical surveillance
      (every two to three years). Sensitivity analyses revealed that the genetic
      testing approach is cost saving for key variables including the kindred size, the
      age of screening onset, and the cost of mutation identification in a proband.
      However, if the APC mutation carriers were monitored at an increased (annual)
      frequency, the cost of the genetic screening strategy increased to $7483/
      pound4677 and was especially sensitive to variability in age of onset of
      screening, family size, and cost of genetic testing of at risk relatives.
      CONCLUSIONS: In FAP kindreds, a predictive genetic testing strategy costs less
      than conventional clinical screening, provided that the frequency of surveillance
      is identical using either strategy. An additional significant benefit is the
      elimination of unnecessary colonic examinations for those family members found to
      be non-carriers.

PMID- 10205209
TI  - Expression of the insulin-like growth factors and their receptors in
      adenocarcinoma of the colon.
AB  - AIMS: To study changes in the expression of insulin-like growth factors (IGFs)
      and their receptors, as well as production of the IGF-I and IGF-II polypeptides,
      in adenocarcinoma of the colon. METHODS: Malignant tissue obtained at operation
      was used. Total RNA was extracted and specific IGF-I and IGF-II and their
      receptor mRNAs were measured by a solution hybridisation RNase protection assay.
      IGF-I and IGF-II polypeptides were measured by specific immunoassays. RESULTS:
      All normal tissues expressed IGF-II, IGF-I receptor, and IGF-II/mannose-6
      phosphate (Man-6-P) receptor. IGF-I mRNA could not be detected but the
      polypeptide was present in small but equal amounts in normal and malignant
      tissue. IGF-II was expressed 40 times more abundantly in colonic tumours than in
      adjacent normal tissue and the concentration of the corresponding polypeptide was
      twice as high in the malignant tissue. IGF-I receptor expression was increased by
      a factor of 2.5 and IGF-II/Man-6-P receptor by a factor of 4. CONCLUSIONS: This
      study confirms that in adenocarcinoma of the human colon there is increased
      expression of IGF-I receptor and IGF-II. Furthermore, IGF-II/Man-6-P receptor
      message is increased and the increase in IGF-II message is accompanied by a
      doubling of the IGF-II protein in the tumour tissue compared with the adjacent
      normal tissue. These findings suggest that the IGF-II/Man-6-P receptor may also
      be involved in development of adenocarcinoma of the colon. There is rapidly
      accumulating evidence implicating the IGF system in the development of malignancy
      of the large bowel.

PMID- 10205210
TI  - Vicia faba agglutinin, the lectin present in broad beans, stimulates
      differentiation of undifferentiated colon cancer cells.
AB  - BACKGROUND: Dietary lectins can alter the proliferation of colonic cells.
      Differentiation is regulated by adhesion molecules which, being glycosylated, are
      targets for lectin binding. AIMS: To examine the effects of dietary lectins on
      differentiation, adhesion, and proliferation of colorectal cancer cells. METHODS:
      Differentiation was assessed in three dimensional gels, adhesion by aggregation
      assay, and proliferation by 3H thymidine incorporation. The role of the
      epithelial cell adhesion molecule (epCAM) was studied using a specific monoclonal
      antibody in blocking studies and Western blots. The human colon cancer cell lines
      LS174T, SW1222, and HT29 were studied. RESULTS: The cell line LS174T
      differentiated in the presence of Vicia faba agglutinin (VFA) into gland like
      structures. This was inhibited by anti-epCAM monoclonal antibody. Expression of
      epCAM itself was unaffected. VFA as well as wheat germ agglutinin (WGA) and the
      edible mushroom lectin (Agaricus bisporus lectin, ABL) significantly aggregated
      LS174T cells but peanut agglutinin (PNA) and soybean agglutinin (SBA) did not.
      All lectins aggregated SW1222 and HT29 cells. Aggregation was blocked by the
      corresponding sugars. Aggregation of cells by VFA was also inhibited by anti
      epCAM. VFA, ABL, and WGL inhibited proliferation of all the cell lines; PNA
      stimulated proliferation of HT29 and SW1222 cells. In competition studies all
      sugars blocked aggregation and proliferation of all cell lines, except that the
      addition of mannose alone inhibited proliferation. CONCLUSION: VFA stimulated an
      undifferentiated colon cancer cell line to differentiate into gland like
      structures. The adhesion molecule epCAM is involved in this. Dietary or
      therapeutic VFA may slow progression of colon cancer.

PMID- 10205211
TI  - Comparison of adrenaline injection and bipolar electrocoagulation for the arrest
      of peptic ulcer bleeding.
AB  - BACKGROUND: Peptic ulcers with active bleeding or a non-bleeding visible vessel
      require aggressive endoscopic treatment. AIMS: To determine whether endoscopic
      adrenaline injection alone or contact probe therapy following injection is a
      suitable treatment for peptic ulcer bleeding. METHODS: A total of 96 patients
      with active bleeding or non-bleeding visible vessels received adrenaline alone,
      bipolar electrocoagulation alone, or combined treatment (n=32 in each group).
      RESULTS: Initial haemostasis was not achieved in one patient in the adrenaline
      group, two in the gold probe group, and two in the injection gold probe group
      (p>0.1). Rebleeding episodes were fewer in the injection gold probe group (2/30,
      6.7%) than in the gold probe group (9/30, 30%, p=0.04) and in the adrenaline
      group (11/31, 35.5%, p=0.01). Treatment failure (other therapy required) was
      rarer in the injection gold probe group (4/32, 12.5%) than in the adrenaline
      group (12/32, 37.5%, p=0.04). The volume of blood transfused after entry of the
      study was less in the injection gold probe group (mean 491 ml) than in the
      adrenaline group (1548 ml, p<0. 0001) and the gold probe group (1105 ml, p<0.01).
      Duration of hospital stay, numbers of patients requiring urgent surgery, and
      death rate were not statistically different among the three groups. CONCLUSIONS:
      For patients with peptic ulcer bleeding, combined adrenaline injection and gold
      probe treatment offers an advantage in preventing rebleeding and decreasing the
      need for blood transfusion.

PMID- 10205212
TI  - Endoscopic ultrasound guided fine needle aspiration biopsy: a large single centre
      experience.
AB  - BACKGROUND: Endoscopic ultrasound guided fine needle aspiration biopsy (EUS-FNA)
      is a recent innovation in the evaluation of gastrointestinal and pulmonary
      malignancies. AIMS: To review the experience with EUS-FNA of a large single
      centre. METHODS: 333 consecutive patients underwent EUS-FNA. Follow up data were
      available on 327 lesions in 317 patients, including 160 lymph nodes, 144
      pancreatic lesions, 15 extraintestinal masses, and eight intramural tumours.
      RESULTS: A primary diagnosis of malignancy was obtained by EUS-FNA in 62% of
      patients with clinically suspicious lesions. The overall accuracy of EUS-FNA for
      the diagnosis of malignancy was 86%, with sensitivity of 84% and specificity of
      96%. With respect to lesion types, the sensitivity, specificity, and accuracy
      were 85%, 100%, and 89% for lymph nodes; 82%, 100%, and 85% for pancreatic
      lesions; 88%, 100%, and 90% for perirectal masses; and 50%, 25%, and 38% for
      intramural lesions, respectively. Compared with size and sonographic criteria,
      EUS-FNA in the evaluation of lymph nodes provided superior accuracy and
      specificity, without compromising sensitivity. Inadequate specimens were obtained
      from only six patients, including 3/5 with stromal tumors. Only one complication
      occurred. CONCLUSIONS: EUS-FNA is safe and can readily obtain tissue specimens
      adequate for cytopathological diagnoses. Compared with size and sonographic
      criteria, it is a superior modality for the detection of nodal metastases. While
      providing accurate diagnosis of pancreatic and perirectal malignancies, results
      suggest the technique is less useful for intramural lesions.

PMID- 10205213
TI  - Randomised controlled trial shows that glyceryl trinitrate heals anal fissures,
      higher doses are not more effective, and there is a high recurrence rate.
AB  - BACKGROUND: Topical application of glyceryl trinitrate (GTN) ointment heals
      chronic anal fissures, providing an alternative to the traditional first line
      treatment of surgical sphincterotomy. AIMS: To determine the most effective dose
      of topical GTN for treatment of chronic anal fissures and to assess long term
      results. METHODS: Seventy consecutive patients with chronic anal fissure, were
      randomly allocated to eight weeks treatment with placebo, 0.2% GTN three times
      daily, or GTN starting at 0.2% with weekly 0.1% increments to a maximum of 0.6%,
      in a double blind study. RESULTS: After eight weeks fissure had healed in 67% of
      patients treated with GTN compared with 32% with placebo (p=0.008). No
      significant difference was seen between the two active treatments. Headaches were
      reported by 72% of patients on GTN compared with 27% on placebo (p<0.001).
      Maximum anal sphincter pressure reduced significantly from baseline by GTN
      treatment (p=0.02), but not placebo (p=0.8). Mean pain scores were lower after
      treatment with GTN compared with placebo (NS). Of fissures healed with placebo
      43% recurred, compared with 33% of those healed with 0.2% GTN and 25% healed with
      escalating dose GTN (p=0.7). CONCLUSIONS: GTN is a good first line treatment for
      two thirds of patients with anal fissure. An escalating dose of GTN does not
      result in earlier healing. Significant recurrence of symptomatic fissures and a
      high incidence of headaches are limitations of the treatment.

PMID- 10205214
TI  - The natural history of histologically proved drug induced liver disease.
AB  - BACKGROUND: The long term outcome of drug related liver disease is unknown. AIMS:
      To study the natural history of histologically proved drug induced
      hepatotoxicity. METHODS: 110 patients with liver biopsies coded either as drug
      induced liver disease or hepatitis/cholestasis of unknown aetiology were
      identified from hospital records 1978-1996. Review of case notes and histology
      identified 44 patients with definite drug induced hepatotoxicity. Forty surviving
      patients were invited to attend a follow up clinic. History, examination, full
      liver screen, and isotope and ultrasound liver scans were repeated in all
      patients. Repeat liver biopsies were offered to patients with abnormal liver
      tests. RESULTS: Presentation at index biopsy was jaundice in 24 patients,
      abnormal liver tests in 17, and hepatic failure in three. Antibiotics (n=13) and
      non-steroidal anti-inflammatory drugs (n=11) were the most common drugs
      implicated. Initial histology showed acute hepatitis in six, chronic hepatitis in
      20, and cholestasis in 18. At 1-19 years (median 5 years) follow up, 13/33 (39%)
      patients had persistent significant abnormalities in their liver blood tests
      and/or scans. Three of the five repeat liver biopsies performed showed
      significant abnormalities. Factors predicting persistence or development of
      chronic liver disease were fibrosis and continued exposure to the drug.
      CONCLUSIONS: Drugs should be considered in the differential diagnosis of abnormal
      liver function and/or histology, as failure to withdraw the offending drug is
      associated with a high risk of persistent liver damage.

PMID- 10205215
TI  - Risk of primary biliary liver cirrhosis in patients with coeliac disease: Danish
      and Swedish cohort data.
AB  - BACKGROUND: Several case reports, but only a few studies, have examined the
      coexistence of coeliac disease and primary biliary cirrhosis. AIM: To estimate
      the risk of primary biliary cirrhosis in two national cohorts of patients with
      coeliac disease in Denmark and Sweden. METHODS: Through record linkage all Danish
      patients hospitalised with coeliac disease were followed for possible occurrence
      of primary biliary cirrhosis from 1 January 1977 until 31 December 1992. All
      patients hospitalised with coeliac disease in Sweden from 1987 to 1996 were also
      followed in a separate analysis. RESULTS: A total of 896 patients with coeliac
      disease were identified in Denmark with a median follow up period of 9.1 years
      for a total of 8040 person-years at risk. Two cases of primary biliary cirrhosis
      were observed where 0.07 were expected, giving a standardised incidence ratio of
      27.6 (95% confidence interval 2.9 to 133.5). A total of 7735 patients with
      coeliac disease were identified in Sweden with a median follow up period of 5.1
      years for a total of 39 284 person-years at risk. Twenty two people with primary
      biliary cirrhosis were identified compared with 0.88 expected, giving a
      standardised incidence ratio of 25.1 (95% confidence interval 15.7 to 37.9).
      CONCLUSION: Patients with coeliac disease are at increased risk of having primary
      biliary cirrhosis.

PMID- 10205216
TI  - Gastric antral vascular ectasia in cirrhotic patients: absence of relation with
      portal hypertension.
AB  - BACKGROUND: Portal hypertensive gastropathy and gastric antral vascular ectasia
      (GAVE) are increasingly recognised as separate entities. The pathogenic role of
      portal hypertension for the development of GAVE is still controversial. AIMS: To
      evaluate the effects of portal decompression on chronic bleeding related to GAVE
      in cirrhotic patients. METHODS: Eight patients with cirrhosis and chronic blood
      loss related to GAVE were included. GAVE was defined endoscopically and
      histologically. RESULTS: All patients had severe portal hypertension (mean
      portocaval gradient (PCG) 26 mm Hg) and chronic low grade bleeding. Seven
      patients underwent transjugular intrahepatic portosystemic shunt (TIPS) and one
      had an end to side portacaval shunt. Rebleeding occurred in seven patients. In
      these, TIPS was found to be occluded after 15 days in one patient; in the other
      six, the shunt was patent and the PCG was below 12 mm Hg in five. In the
      responder, PCG was 16 mm Hg. Antrectomy was performed in four non-responders;
      surgery was uneventful, and they did not rebleed after surgery, but two died 11
      and 30 days postoperatively from multiorgan failure. In one patient, TIPS did not
      control GAVE related bleeding despite a notable decrease in PCG. This patient
      underwent liver transplantation 14 months after TIPS; two months after
      transplantation, bleeding had stopped and the endoscopic appearance of the antrum
      had normalised. CONCLUSIONS: Results suggest that GAVE is not directly related to
      portal hypertension, but is influenced by the presence of liver dysfunction.
      Antrectomy is a therapeutic option when chronic bleeding becomes a significant
      problem but carries a risk of postoperative mortality.

PMID- 10205217
TI  - Cardiac function and haemodynamics in alcoholic cirrhosis and effects of the
      transjugular intrahepatic portosystemic stent shunt.
AB  - BACKGROUND: A portosystemic stent shunt may impair cardiac function and
      haemodynamics. AIMS: To investigate the effects of a transjugular intrahepatic
      portosystemic shunt (TIPS) on cardiac function and pulmonary and systemic
      circulation in patients with alcoholic cirrhosis. PATIENTS/METHODS: 17 patients
      with alcoholic cirrhosis and recent variceal bleeding were evaluated by
      echocardiography and catheterisation of the splanchnic and pulmonary circulation
      before and after TIPS. The period of catheter measurement was extended to nine
      hours in nine of the patients. The portal vein was investigated by Doppler
      ultrasound before and nine hours after TIPS. RESULTS: Baseline echocardiography
      showed the left atrial diameter to be slightly increased and the left ventricular
      volume to be in the upper normal range. Nine hours after TIPS, the left atrial
      diameter and left ventricular end diastolic volume were increased (by 6% (p<0.01)
      and 7% (p<0.01) respectively); end systolic volume had not changed significantly.
      Invasive measurements showed a sharp increase in right atrial pressure (by 101%;
      p<0.01), mean pulmonary artery pressure (by 92%; p<0.01), pulmonary capillary
      wedge pressure (by 111%; p<0.01), and cardiac output (8.1 (1.6) to 11.9 (2.4)
      l/min; p<0.01). Systemic vascular resistance decreased (824 (242) to 600 (265)
      dyn.s.cm-5 p<0.01), and total pulmonary resistance increased (140 (58.5) to 188
      (69.5) dyn.s.cm-5; p<0.05). Total pulmonary resistance (12%; NS), cardiac output
      (1.4 l/min; p<0. 05), and portal vein blood flow (1.4 l/min; p<0.05) remained
      elevated for nine hours after TIPS in the subgroup. Portoatrial pressure gradient
      (43%; p<0.05), portohepatic vascular resistance (72%; p<0.05), and systemic
      vascular resistance (27%; p<0.01) were consistently reduced. CONCLUSIONS: The
      increase in the left atrial diameter, the pulmonary capillary wedge pressure, and
      total pulmonary resistance observed after the TIPS procedure reflected diastolic
      dysfunction of the hyperdynamic left ventricle in patients with alcoholic
      cirrhosis. The haemodynamic effects of the portosystemic stent shunt itself on
      the splanchnic circulation seem to be mainly responsible for the further decrease
      in systemic vascular resistance. TIPS may unmask a coexisting preclinical
      cardiomyopathy in patients with alcoholic cirrhosis and portal hypertension.

PMID- 10205219
TI  - Thrombopoietin concentrations are low in patients with cirrhosis and
      thrombocytopenia and are restored after orthotopic liver transplantation.
AB  - BACKGROUND: Thrombocytopenia in cirrhotic patients may be due to deficient
      production of thrombopoietin. AIMS: To determine the relation between
      thrombopoietin and thrombocytopenia in cirrhotic patients before and after
      orthotopic liver transplantation. METHODS: Thrombopoietin concentrations and
      platelet counts were measured in 43 cirrhotic patients and 21 normal controls and
      serially for 14 days after transplantation in 23/43 patients. RESULTS: 27 of the
      43 patients had thrombocytopenia (platelet count less than 120 x 10(9)/l; group
      1) whereas 16 patients had normal platelet count (group 2). Thrombopoietin
      concentrations were lower in group 1 than in group 2 (92.5 (20.3-286.3) v 226.6
      (30.1-848.3) pg/ml, p=0.003) and normal controls (92.5 (20.3-286.3) v 158.3 (22.5
      232.9) pg/ml, p=0.028). Post-transplantation thrombopoietin concentrations
      increased with a peak at day 5. The rise was significant in patients with low
      pretransplantation platelet count (89.1 (21.29-247.6) to 545.1 (66.2-2569) pg/ml;
      n=16, p=0.001) but not in those with normal platelet count (262.8 (30.1-848.3) to
      315.1 (114-954.6) pg/ml; n=7, p=0.47). No correlation was found
      pretransplantation between spleen volume and platelet count (r=-0.11, p=0.6) or
      thrombopoietin concentrations (r=-0.04, p=0.8). However, pretransplantation
      thrombopoietin concentrations correlated with platelet count (r=0.47, p=0.0015),
      whereas an inverse correlation was found between peak thrombopoietin
      concentrations and nadir platelet count (r=-0.41 p=0. 049) post-transplantation.
      CONCLUSIONS: Inadequate thrombopoietin production may contribute to cirrhotic
      thrombocytopenia. Thrombopoietin production is restored after liver
      transplantation leading to the resolution of thrombocytopenia.

PMID- 10205218
TI  - Hepatic and splanchnic nitric oxide activity in patients with cirrhosis.
AB  - BACKGROUND: In animal models of cirrhosis, altered activity of nitric oxide (NO)
      has been implicated in the pathogenesis of increased intrahepatic portal vascular
      resistance and abnormal mesenteric vasodilatation. AIMS: To investigate NO
      activity in the liver and splanchnic vascular bed of patients with cirrhosis.
      METHODS: Activity of the calcium dependent constitutive and calcium independent
      inducible isoforms of NO synthase (cNOS and iNOS, respectively) was assayed
      biochemically in biopsy specimens of liver and a vascular portion of the greater
      omentum (representative of mesenteric vasculature) obtained from patients with
      cirrhosis undergoing liver transplantation (n=14) and non-cirrhotic control
      patients undergoing liver resection for metastases (n=9). The concentration of NO
      metabolites (NO2 + NO3) in portal and peripheral venous plasma was measured.
      RESULTS: The activity of cNOS was lower in cirrhotic compared with non-cirrhotic
      subjects for both liver and omentum. Hepatic and omental iNOS activities did not
      differ significantly between the two groups. Portal (NO2 + NO3) was threefold
      higher in cirrhotic than non-cirrhotic patients, but no differences were observed
      in systemic venous samples from the two groups. CONCLUSIONS: The activity of cNOS
      is diminished in the cirrhotic human liver. The resultant decrease in
      constitutive NO release may promote an increase in the intrahepatic portal
      vascular resistance. Elevated portal venous (NO2 + NO3) indicates enhanced
      splanchnic vascular release of NO in cirrhotic patients, but the absence of
      increased NOS activity in the mesenteric vasculature suggests differential
      regulation of NO synthesis within the splanchnic vascular bed.

PMID- 10205224
TI  - Nitric oxide synthase genes: candidate genes among many others.

PMID- 10205220
TI  - Mechanisms of immune escape in viral hepatitis.

PMID- 10205223
TI  - Hypertension : the third five years 

PMID- 10205225
TI  - Different frequencies of inducible nitric oxide synthase genotypes in older
      hypertensives.
AB  - A locus for essential hypertension has been found recently on chromosome 17 in
      the general vicinity of the inducible nitric oxide synthase (iNOS) gene (NOS2A at
      17cen-q11.2). We therefore tested NOS2A markers for association and linkage with
      hypertension in affected Australian Anglo-Caucasians. Patients for the
      association study (n=112) were from our cohort of hypertensives
      (systolic/diastolic=175+/-25 SD/112+/-19 mm Hg) who were the offspring of 2
      hypertensive parents; control subjects (n=164) were normotensives whose parents
      were both normotensive. The linkage study involved 156 hypertensive sib-pairs.
      Genotypes for an 8-allele pentameric repeat located 2.6 kb upstream of NOS2A and
      of a biallelic tetranucleotide repeat 0.7 kb upstream were determined by
      polymerase chain reaction and automated gene scan analysis. In the association
      study, the frequency of the minor allele of the biallelic marker was 0.18 in the
      hypertensives and 0.14 in the normotensives (chi21 df=1.1, P=0.3). Allele
      frequencies for the multiallelic marker were also similar in each group (chi2 7
      df=9.8, P=0.2). Furthermore, no genotypic differences in blood pressure were
      apparent. In the sib-pair study, SPLINK APM, and MAPMAKERS/SIBS did not indicate
      excess allele sharing. We also examined genotype as a function of age. In the
      younger (< 60 years) hypertensives as well as younger or older normotensives,
      genotype and allele frequency of the biallelic marker was similar (0.12 to 0.14).
      However, in hypertensives >/=60 years of age, frequency of the minor allele was
      0.28 (chi2=7.4, P=0.006). Homozygotes for this allele were rare. Frequency of
      heterozygotes was 0.19 for normotensives but 0.39 for the older hypertensives
      (chi2=8.0, P=0.018) and was 0.40 for hypertensive sibs >/=60 years of age with a
      diastolic pressure >/=100 mm Hg. Furthermore, homozygotes for the major allele
      were 7 years younger than heterozygotes (P=0.05 by ANOVA). In conclusion, the
      present study shows (1) no evidence for a role of NOS2A in hypertension and (2) a
      genotypic difference in frequency of a NOS2A promoter variant in older
      hypertensives, seen in 2 different cohorts. A possible interpretation of the
      latter observation is that NOS2A genotype could affect longevity, at least in
      patients at high risk by having moderate to severe hypertension.

PMID- 10205226
TI  - Lack of evidence for association between the endothelial nitric oxide synthase
      gene and hypertension.
AB  - Significant association between a Glu298Asp polymorphism of the endothelial
      nitric oxide synthase (eNOS) gene and essential hypertension was recently
      reported in Japanese populations, with the 298Asp variant showing a higher
      prevalence in hypertensive patients (10.3% to 12.0%) than in normotensive
      subjects (5.0% to 5.8%). In contrast, another study demonstrated that the 298Glu
      variant was significantly associated with hypertension in a Caucasian population.
      We therefore undertook an extensive association study in Japanese to resolve
      these contradictory claims. A total of 1165 individuals were selected from clinic
      outpatients and hospital staff in a single institution. The relevance of the
      Glu298Asp polymorphism to hypertension in this population was tested in 2 ways.
      First, a case-control study was conducted in 549 hypertensive and 513
      normotensive subjects within the study population, with the chi2 statistic used
      to test the significance of an association between eNOS genotype and the presence
      of hypertension. Second, an ANOVA was used to test the significance of an
      association between eNOS genotype and the level of blood pressure within the
      entire population except for 167 hypertensive subjects who had been under
      treatment for hypertension. No significant association was observed in either of
      the statistics tested. Allele frequencies of 298Asp were concordant across the
      panels: 8.4% in hypertensive subjects, 8. 2% in normotensive subjects, and 7.9%
      and 9.5% in 2 additional sample populations used as reference panels. Taken
      together, our results do not support the previous observation that the molecular
      variant of the eNOS gene may confer principal susceptibility for essential
      hypertension but rather suggest the existence of sampling variation.

PMID- 10205229
TI  - Genetic determination of cardiac mass in normotensive rats: results from an
      F344xWKY cross.
AB  - Genetic determinants affect adult cardiac mass and the predisposition to develop
      cardiac hypertrophy. The aim of this study was to identify quantitative trait
      loci (QTL) that control heart and left ventricular (LV) weight by use of
      normotensive inbred rat strains that differ in their adult cardiac mass
      phenotype. We studied 126 male F2 rats derived from a cross of normotensive
      Wistar-Kyoto and Fischer 344 rats. At 12 weeks of age, total heart weight and LV
      weight were measured. Genomic DNA from these animals was screened by use of
      polymorphic microsatellite markers across the whole genome (excluding the sex
      chromosomes). In this cross, the genetic contribution to total heart weight
      variation was 56%, and the genetic contribution for LV weight was 55%. Using the
      Mapmaker/QTL computer package, we identified a significant QTL on chromosome 3
      with a log10 likelihood (LOD) score of 4.8, which accounted for 16.5% of the
      total variance of LV weight. This QTL was centered close to the marker D3Rat29.
      The QTL was also found to be significantly linked with total heart weight
      (LOD=4.4). These data provide the first demonstration of a QTL on chromosome 3
      that plays a role in determining the difference in LV mass between normotensive
      Fischer 344 and Wistar- Kyoto inbred rat strains. The prostaglandin synthase 1
      gene is located within the QTL.

PMID- 10205228
TI  - Troglitazone upregulates nitric oxide synthesis in vascular smooth muscle cells.
AB  - We investigated the effects of troglitazone on cytokine-stimulated nitric oxide
      (NO) production in cultured rat vascular smooth muscle cells (VSMC). The increase
      in NO formation caused by interleukin-1alpha (IL-1) was enhanced by troglitazone
      in a concentration-dependent manner. Bacterial lipopolysaccharide-stimulated NO
      synthesis was also increased by troglitazone. The combinations of IL-1, tumor
      necrosis factor-alpha, or lipopolysaccharide with interferon-gamma (IFN) were
      strong stimuli for induction of NO synthesis in VSMC, which were further
      potentiated by the presence of troglitazone. When troglitazone was added at
      increasing intervals after the stimulation of VSMC with IL-1, the enhancement in
      NO production decreased as the interval lengthened, suggesting that troglitazone
      alters NO synthase (NOS) expression by VSMC rather than having a direct affect on
      VSMC NOS activity. Troglitazone had no effect on IL-1-elicited or IL-1/IFN
      elicited nuclear factor-kappaB activity in VSMC. Troglitazone inhibited the
      degradation of cytokine-induced NOS mRNA. Thus troglitazone appears to enhance IL
      1-induced NOS mRNA levels by prolonging its half-life rather than activating its
      transcription, which is nuclear factor -kappaB-dependent. No expression of
      peroxisome proliferator-activated receptor-gamma (PPARgamma) was detected in
      VSMC, and 15-deoxy-D12,14 prostaglandin J2, the natural ligand for the PPARgamma,
      did not resemble the effect of troglitazone on IL-1-induced NO synthesis. These
      results indicate that troglitazone upregulates cytokine-stimulated NO synthesis
      in VSMC through PPARgamma-independent mechanisms. Considering its inhibitory
      effects on the action of numerous growth factors on VSMC, the direct vascular
      effects of troglitazone shown in this study may have important implications for
      prevention of restenosis and possibly atherosclerosis.

PMID- 10205227
TI  - A large blood pressure-raising effect of nitric oxide synthase inhibition in
      humans.
AB  - In experimental animals, systemic administration of nitric oxide synthase (NOS)
      inhibitors causes large increases in blood pressure that are in part
      sympathetically mediated. The aim of this study was to determine the extent to
      which these conclusions can be extrapolated to humans. In healthy normotensive
      humans, we measured blood pressure in response to two NOS inhibitors, NG
      monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine methyl ester (L-NAME), the
      latter of which recently became available for use in humans. The major new
      findings are 3-fold. First, L-NAME produced robust increases in blood pressure
      that were more than 2 times larger than those previously reported in humans with
      L-NMMA and approximated those seen in experimental animals. L-NAME (4 mg/kg)
      raised mean arterial pressure by 24+/-2 mm Hg (n=27, P<0.001), whereas in
      subjects who received both inhibitors, a 12-fold higher dose of L-NMMA (50 mg/kg)
      raised mean arterial pressure by 15+/-2 mm Hg (n=4, P<0.05 vs L-NAME). Second,
      the L-NAME-induced increases in blood pressure were caused specifically by NOS
      inhibition because they were reversed by L-arginine (200 mg/kg, n=12) but not D
      arginine (200 mg/kg, n=6) and because NG-nitro-D-arginine methyl ester (4 mg/kg,
      n=5) had no effect on blood pressure. Third, in humans, there is an important
      sympathetic component to the blood pressure-raising effect of NOS inhibition.
      alpha-Adrenergic blockade with phentolamine (0.2 mg/kg, n=9) attenuated the L
      NAME-induced increase in blood pressure by 40% (P<0.05). From these data, we
      conclude that pharmacological inhibition of NOS causes large increases in blood
      pressure that are in part sympathetically mediated in humans as well as
      experimental animals.

PMID- 10205230
TI  - Chronic ETA receptor blockade attenuates cardiac hypertrophy independently of
      blood pressure effects in renovascular hypertensive rats.
AB  - In isolated cardiac myocytes, the direct effects of angiotensin II on cellular
      growth and gene expression were shown to be mediated by endothelin via the
      endothelin subtype A (ETA) receptor. To determine whether this pathway is also
      involved in the cardiovascular adaptations to a chronic activation of the renin
      angiotensin system in vivo, the effects of a selective ETA receptor antagonist
      (LU 127043) were investigated in adult rats with renal artery stenosis. Four
      groups of rats (n=107) were studied over a period of 10 days after surgery: (1)
      sham-operated animals with saline administration, (2) rats subjected to left
      renal artery clipping with saline administration, (3) sham-operated rats with LU
      127043 administration, and (4) rats subjected to left renal artery clipping with
      LU 127043 administration. LU 127043 (50 mg/kg) or saline was given by gavage
      twice daily starting 1 day before the operation. In clipped rats with saline
      administration, plasma renin activity, the ratio of left ventricular weight to
      body weight, and mRNAs for beta-myosin heavy chain and atrial natriuretic peptide
      were significantly elevated as early as 2 days after surgery. Blood pressure
      started to rise on the third postoperative day and attained a steady state
      hypertensive level by day 6. Blockade of ETA receptors had no effects on plasma
      renin activity or the time course of hypertension in clipped animals but
      completely prevented left ventricular hypertrophy and the re-expression of the
      beta-myosin heavy chain and atrial natriuretic peptide genes on day 2. While the
      expressions of the beta-myosin heavy chain and atrial natriuretic peptide genes
      were not different from saline-treated, clipped animals after day 4, the
      development of left ventricular hypertrophy remained markedly blunted (-50%)
      during ETA receptor blockade until day 10. These results show that a continuous
      blockade of ETA receptors significantly attenuates the development of left
      ventricular hypertrophy and, more transiently, fetal gene expression in the early
      phase of renovascular hypertension. Since neither blood pressure nor the increase
      in plasma renin activity was significantly altered by ETA receptor blockade, the
      inhibitory influences of the ETA receptor antagonist on left ventricular
      hypertrophy and gene expression were mediated most likely through a direct
      blockade of myocardial ETA receptors.

PMID- 10205231
TI  - Effects of candesartan and cilazapril on rats with myocardial infarction assessed
      by echocardiography.
AB  - The purpose of this study was to compare the angiotensin II type 1 receptor
      antagonist candesartan cilexitil (candesartan) and the angiotensin-converting
      enzyme inhibitor cilazapril on cardiac function, assessed by Doppler
      echocardiography and cardiac gene expression associated with cardiac remodeling,
      in rats with myocardial infarction. Candesartan or cilazapril was administered
      after myocardial infarction. At 1 and 4 weeks after myocardial infarction,
      cardiac function and mRNA expression in noninfarcted myocardium were analyzed.
      Candesartan and cilazapril equally prevented increases in hypertrophy in
      noninfarcted myocardium, left ventricular dilatation, and ejection fraction at 4
      weeks. The E-wave/A-wave velocity ratio and the rate of E-wave deceleration,
      measures of diastolic function, increased to 9.2+/-0.6 and 26.3+/-2. 6 m/s2 at 1
      week after myocardial infarction. Candesartan and cilazapril, administered at a
      dose of 1 mg/kg per day, prevented increases in E-wave/A-wave velocity ratio and
      E-wave deceleration at 1 and 4 weeks. Candesartan and cilazapril significantly
      suppressed increased mRNA expression of beta-myosin heavy chain, alpha-skeletal
      actin, and atrial natriuretic peptide in noninfarcted ventricle at 1 and 4 weeks
      and expression of collagen I and III at 4 weeks to a similar extent. When given
      at a dose of 10 mg/kg per day, both candesartan and cilazapril prevented cardiac
      dysfunction and gene expression to the same extent as when given at 1 mg/kg per
      day. In conclusion, Doppler echocardiography showed that candesartan and
      cilazapril equally improved systolic and diastolic function and that ventricular
      remodeling accompanied modulation of cardiac gene expression.

PMID- 10205232
TI  - Enhanced natriuretic response to neutral endopeptidase inhibition in heart
      transplant recipients.
AB  - Heart-transplant recipients (Htx) generally present with body fluid and sodium
      handling abnormalities and hypertension. To investigate whether neutral
      endopeptidase inhibition (NEP-I) increases endogenous atrial natriuretic peptide
      (ANP) and enhances natriuresis and diuresis after heart transplantation,
      ecadotril was given orally to 8 control subjects and 8 matched Htx, and levels of
      volume-regulating hormones and renal water, electrolyte, and cyclic guanosine
      monophosphate (cGMP) excretions were monitored for 210 minutes. Baseline plasma
      ANP, brain natriuretic peptide (BNP), and cGMP were elevated in Htx, but renin
      and aldosterone, like urinary parameters, did not differ between groups. NEP-I
      increased plasma ANP (Htx, 20.6+/-2.3 to 33.2+/-5.9 pmol/L, P<0.01; controls,
      7.7+/-1. 2 to 10.6+/-2.6 pmol/L) and cGMP, but not BNP. Renin decreased similarly
      in both groups, whereas aldosterone decreased significantly only in Htx. Enhanced
      urinary sodium (1650+/-370% versus 450+/-150%, P=0.01), cGMP, and water
      excretions were observed in Htx and urinary cGMP positively correlated with
      natriuresis in 6 of the Htx subjects. Consistent with a normal circadian rhythm
      of blood pressure, without excluding a possible effect of NEP-I, mean systemic
      blood pressure increased similarly in both groups at the end of the study (6.9+/
      2.0% versus 7.4+/-2.8% in controls and Htx). Thus, systemic hypertension, mild
      renal impairment, and raised plasma ANP levels are possible contributory factors
      in the enhanced natriuresis and diuresis with NEP-I in Htx. These results support
      a physiological role for the cardiac hormone after heart transplantation and
      suggest that long-term studies may be useful to determine the potential of NEP-I
      in the treatment of sodium retention and water retention after heart
      transplantation.

PMID- 10205233
TI  - Angiotensin II type 1 receptor antagonist downregulates nonmuscle myosin heavy
      chains in spontaneously hypertensive rat aorta.
AB  - The aim of this study was to clarify the differences between the angiotensin II
      type 1 (AT1) receptor antagonist and the angiotensin-converting enzyme (ACE)
      inhibitor on smooth muscle and nonmuscle myosin heavy chain isoforms in aortic
      smooth muscle cells of Wistar-Kyoto rats and spontaneously hypertensive rats. All
      4 myosin heavy chain isoforms are heterogeneously expressed in the smooth muscle
      cells of the aortic tunica media in 20-week-old rats, and the contractile-type
      myosin heavy chains are highly expressed in smooth muscle cells of the aortic
      tunica media compared with the synthetic-type myosin heavy chains. Both the AT1
      receptor antagonist and the ACE inhibitor had the same effects on hemodynamics,
      smooth muscle cell hypertrophy and proliferation, fibrosis, and vascular
      remodeling in spontaneously hypertensive rats. However, the AT1 receptor
      antagonist had a more potent effect on the downregulation of the synthetic-type
      myosin heavy chains than the ACE inhibitor in spontaneously hypertensive rat
      aortic tunica media. In contrast, these effects of the AT1 receptor antagonist
      and the ACE inhibitor on hemodynamics, morphology, fibrosis, and expression of
      myosin heavy chain isoforms in smooth muscle cells of the aortic tunica media
      were not observed in Wistar-Kyoto rats. Thus, within 6 weeks, the AT1 receptor
      antagonist might modulate the cellular composition of myosin heavy chain isoforms
      in smooth muscle cells more efficiently than the ACE inhibitor, without
      morphological changes in the spontaneously hypertensive rat aorta.

PMID- 10205234
TI  - Angiotensin AT1 receptor subtype as a cardiac target of aldosterone: role in
      aldosterone-salt-induced fibrosis.
AB  - This study tests the hypothesis that aldosterone induces cardiac fibrosis through
      an increase of cardiac angiotensin II (Ang II) AT1 receptor levels, thereby
      potentiating the fibrotic effect of Ang II by determining the effects of
      spironolactone and losartan on cardiac fibrosis, AT1 density, and gene expression
      in aldosterone-salt-treated rats. Fibrosis was quantified by slot blots of
      collagen I and III mRNA levels and videomorphometry of Sirius red-stained
      collagen. AT1 receptor density was determined by (125I-Sar1-Ile8)-Ang II
      competition binding, and AT1 mRNA levels were analyzed by quantitative reverse
      transcriptase polymerase chain reaction. One month of aldosterone-salt treatment
      induced a decrease in plasma Ang II and an increase in blood pressure, left
      ventricular hypertrophy, and ventricular fibrosis. Spironolactone (20 mg/kg per
      day) and losartan spironolactone (10 mg/kg per day) had no effect on the first 3
      parameters. Losartan was as effective as spironolactone in preventing ventricular
      collagen mRNA increase and fibrosis. Ventricular density of AT1 receptors
      increased 2-fold and was accompanied by a 3-fold increase in the corresponding
      mRNA in aldosterone-salt compared with sham-operated rats. Both spironolactone
      and losartan prevented the elevation of ventricular AT1 density and that of right
      ventricular AT1 mRNA levels. These results demonstrate that the mechanism by
      which aldosterone-salt induces cardiac fibrosis involves Ang II acting through
      AT1 receptors. They also suggest that the cardiac AT1 receptor is a target for
      aldosterone.

PMID- 10205235
TI  - Arterial baroreflex control of the sinus node during dobutamine exercise stress
      testing.
AB  - The contributions of increases in circulating catecholamines, changes in central
      command, and muscle afferents on baroreflex control of the sinus node during
      exercise are unclear. We used a dobutamine infusion to induce hemodynamic changes
      comparable to those of moderate physical exercise in the absence of changes in
      central command and muscle afferents in 13 healthy subjects. Dobutamine (up to 9
      microg/kg body weight per minute) increased systolic blood pressure, shortened
      the RR interval, increased systolic blood pressure variability, but blunted RR
      interval variability (P<0.05 versus placebo). Consequently, dobutamine decreased
      the coherence between variations in systolic blood pressure and RR interval and
      decreased arterial baroreflex sensitivity from 12+/-2 to 3+/-1 ms/mm Hg (P<0.01).
      The largest increases in systolic blood pressure with dobutamine were paralleled
      by the greatest impairments in arterial baroreflex sensitivity (0. 50<r<0.56,
      P<0.01). The chronotropic effects of dobutamine prevented a reflex bradycardia in
      response to the blood pressure increase. However, less predominant low-frequency
      oscillations in systolic blood pressure (P<0.0001) suggested preserved
      sympathetic withdrawal in response to the blood pressure increase induced by
      dobutamine. In conclusion, this study revealed that a shift in the operating
      point of the arterial baroreceptors and the chronotropic effects of adrenergic
      stimulation impair baroreflex control of the sinus node during dobutamine
      exercise stress testing. Baroreflex control of the sinus node is not reset when
      hemodynamic characteristics of exercise are reproduced in the absence of
      modifications in central command and muscles afferents.

PMID- 10205236
TI  - Central adrenomedullin augments the baroreceptor reflex in conscious rabbits.
AB  - We examined the roles of central adrenomedullin, proadrenomedullin N-terminal 20
      peptide (PAMP), and calcitonin gene-related peptide (CGRP) on the baroreceptor
      reflex in conscious rabbits. Intracerebroventricular injection of adrenomedullin
      (0.2 and 1 nmol/80 microL) elicited dose-related increases in arterial pressure
      and renal sympathetic nerve activity. On the other hand, a subpressor dose of
      intracerebroventricular infusion of adrenomedullin (1 nmol/300 microL per hour)
      caused significant increases in baroreflex sensitivities assessed by renal
      sympathetic nerve activity and heart rate compared with vehicle infusion (Gmax; 
      14.9+/-1.7 versus -8.0+/-0.7%/mm Hg, P<0.01, and -8.1+/-0.8 versus -5.1+/-0.5
      bpm/mm Hg, P<0.01, respectively). Intracerebroventricular infusion of CGRP (1
      nmol/300 microL per hour), which is structurally homologous to adrenomedullin,
      also enhanced the baroreflex controls of renal sympathetic nerve activity and
      heart rate. However, the intracerebroventricular infusion of PAMP (30 nmol/300
      microL per hour) failed to alter the baseline levels of arterial pressure and
      baroreflex sensitivities. These results suggest that central adrenomedullin and
      CGRP, but not PAMP, participate in cardiovascular regulation to augment the
      baroreflex controls of renal sympathetic nerve activity and heart rate in
      conscious rabbits.

PMID- 10205237
TI  - Structural skin capillary rarefaction in essential hypertension.
AB  - A reduction in the density of capillaries (rarefaction) is known to occur in many
      tissues in patients with essential hypertension. This rarefaction may play a role
      in increasing peripheral resistance. However, the mechanism underlying this
      capillary rarefaction is not understood. The aim of this study was to assess the
      extent of structural versus functional capillary rarefaction in the skin of
      dorsum of fingers in essential hypertension. The capillary microcirculation was
      examined with video microscopy before and after maximizing the number of perfused
      capillaries by venous congestion. The study group comprised 17 patients with
      essential hypertension (mean supine blood pressure, 155/96 mm Hg) and 17 closely
      matched normotensive controls (mean blood pressure, 127/77 mm Hg). We used
      intravital video microscopy with an epi-illuminated microscope to examine the
      skin of the dorsum of left middle phalanx before and after venous congestion at
      60 mm Hg for 2 minutes. A significantly lower mean capillary density occurred at
      baseline in hypertensive subjects versus normotensive subjects. With venous
      occlusion, capillary density increased significantly in both groups; however,
      maximal capillary density remained significantly lower in the hypertensive
      subjects than in the normotensive subjects. The study strongly suggests that much
      of the reduction in capillary density in the hypertensive subjects is caused by
      structural (anatomic) absence of capillaries rather than functional nonperfusion.

PMID- 10205238
TI  - Hypertension in diet versus pharmacologically treated diabetics: mortality over a
      5-year follow-up.
AB  - The natural history of non-insulin-dependent diabetes mellitus (NIDDM) differs
      markedly between patients with diet treated and pharmacologically treated
      disease. However, the interrelationship between hypertension and these common
      diabetes types has not been specifically addressed in previous studies. This
      study was designed to evaluate the prognostic significance and prevalence of
      hypertension in coronary patients with diet versus pharmacologically treated
      NIDDM over a 5-year follow-up period. The study sample comprised 11 515 patients
      aged 45 to 74 years with a previous myocardial infarction and/or anginal syndrome
      who had been screened but were not included in the Bezafibrate Infarction
      Prevention study. Among them, 9033 were nondiabetics and 2482, diabetics (987
      diet treated and 1495 pharmacologically treated). The prevalence of hypertension
      among nondiabetics, diet-treated diabetics, and pharmacologically treated
      diabetics was 31%, 42%, and 43%, respectively. Crude all-cause mortality (CM) was
      lower in the nondiabetic patients (11.2% versus 22.0%; P<0.001). Among diabetics,
      548 patients died: 81 diet treated normotensives (CM 14%); 100 diet-treated
      hypertensives (CM 24.4%); 205 pharmacologically treated normotensives (CM 24.2%);
      and 162 pharmacologically treated hypertensive patients (CM 25.0%). Age-adjusted
      mortality was lowest for the normotensive patients in the diet-treated group and
      highest for the hypertensive pharmacologically treated patients. Multivariate
      analysis shows that hypertension is a strong and independent predictor of
      increased CM in diet-treated but not in pharmacologically treated NIDDM: hazard
      ratio (HR) was 1.68 (95% confidence interval [CI] 1.24 to 2.29) for the diet
      treated versus 1. 01 (95% CI 0.82 to 1.26) for the pharmacologically treated
      diabetics. The contribution of hypertension to stroke mortality was substantial
      for both diet treated and pharmacologically treated NIDDM: hazard ratios were
      3.17 (95% CI 1.12 to 8.98) and 2.21 (95% CI 0.72 to 6.77), respectively. The
      increased risk of mortality associated with hypertension in relatively mild diet
      treated NIDDM strongly supports the clinical benefit of early blood pressure
      control among diabetic patients with ischemic heart disease.

PMID- 10205239
TI  - Blood pressure, sodium intake, insulin resistance, and urinary nitrate excretion.
AB  - The objective of this study was to investigate the relationships among various
      humoral factors thought to be involved in the regulation of blood pressure during
      high NaCl intake. Nineteen healthy subjects underwent sequential 5-day periods
      ingesting a low-sodium (25 mmol/d) or high-sodium (200 mmol/d) diet. Insulin
      resistance was assessed by the steady-state plasma glucose concentration at the
      end of a 3-hour insulin suppression test. Insulin resistance correlated inversely
      with natriuresis (P=0.04) and directly with increase in weight (P=0.03). The
      increase in mean arterial pressure associated with the high-sodium diet
      correlated directly with the gain in weight (P<0.05) and inversely with the
      increase in urinary nitrate excretion (P<0.0001). In a multiple regression model,
      more than 2/3 of the variance in mean arterial pressure was accounted for by the
      gain in weight and change in urinary nitrate excretion. The steady-state plasma
      glucose concentrations obtained with the 2 diets were similar, indicating that
      insulin resistance was unaffected by sodium intake. During high sodium intake,
      plasma renin activity and aldosterone decreased and plasma atrial natriuretic
      peptide increased; these changes did not correlate with the change in mean
      arterial pressure, insulin resistance, or change in urinary nitrate excretion. To
      the extent that urinary nitrate excretion reflects activity of the endogenous
      nitric oxide system, these results suggest that the salt sensitivity of mean
      arterial pressure may be related to blunted generation of endogenous nitric
      oxide. The results also demonstrate that insulin-resistant individuals have an
      impaired natriuretic response to high sodium intake.

PMID- 10205240
TI  - Salt-sensitive hypertension develops after short-term exposure to Angiotensin II.
AB  - We hypothesized that short-term exposure to angiotensin II (Ang II) could result
      in structural and functional changes in the kidney that would favor sodium
      retention and the development of sustained hypertension. To test this hypothesis,
      rats were exposed to pressor doses (435 ng. kg-1. min-1) of Ang II for 2 weeks.
      The infusion of Ang II was associated with acute hypertension, renal dysfunction,
      proteinuria, and focal tubulointerstitial and vascular damage. At sites of the
      tubulointerstitial damage, there was a reduction in peritubular capillary
      endothelial cell staining. By use of immunostaining, we found focal loss of
      endothelial nitric oxide synthase (eNOS) in the peritubular capillaries at sites
      of injury and a generalized reduction in eNOS in collecting ducts, thin loops of
      Henle, and vascular bundles in the medulla. When the Ang II infusion ended, the
      rats became normotensive and renal function returned toward normal. However,
      exposure of the rats to high salt diet (4% NaCl) resulted in the redevelopment of
      hypertension after 3 to 4 weeks. Rats maintained on a high salt diet with no
      prior exposure to Ang II and rats placed on low salt diet (0.1% NaCl) after
      exposure to Ang II remained normotensive. Thus, we report a new model of salt
      sensitive hypertension induced by transient exposure to pressor doses of Ang II.
      The mechanism may relate to microvascular injury with peritubular capillary loss
      coupled with functional changes, such as a loss in intrarenal nitric oxide
      formation, that could alter the ability of the kidney to excrete a salt load.

PMID- 10205241
TI  - Hyponatremic-hypertensive syndrome with renal ischemia: an underrecognized
      disorder.
AB  - Renal artery stenosis or occlusion causing the hyponatremic-hypertensive syndrome
      has been rarely reported. Our impression, however, was that the disorder is not
      uncommon. Case records from patients in one city (population 350 000) presenting
      between 1980 and 1997 with hypertension, hyponatremia, and evidence of renal
      ischemia were scrutinized. Thirty-two patients fulfilling inclusion criteria were
      identified. Admission supine arterial pressures were high (mean 228/124 mm Hg),
      but there was a vigorous fall in pressure on standing (26/12.7 mm Hg recorded in
      27 patients). Mean plasma concentrations of sodium (129.7 mmol/L) and potassium
      (2.7 mmol/L) were low, and 24-hour urine protein excretion was elevated in 19 of
      26 patients. Twenty-two of the 32 patients were female, the majority were
      asthenic, and all but 5 were smokers. Symptoms precipitating hospitalization were
      headache, clouding of consciousness, confusion, weakness, weight loss, thirst,
      and polyuria. Plasma renin levels, measured in 20 patients, were elevated in most
      cases and correlated inversely (r=-0.63, P<0.01) with the plasma sodium
      concentration. The hyponatremic-hypertensive syndrome in patients with renal
      ischemia is not rare: Rather, it is underreported. It tends to affect elderly
      asthenic women who smoke heavily. Stimulation of renin release from the ischemic
      kidney is probably central to the pathophysiology. The syndrome deserves better
      recognition to ensure appropriate investigations and management.

PMID- 10205242
TI  - Local renin-angiotensin system is involved in K+-induced aldosterone secretion
      from human adrenocortical NCI-H295 cells.
AB  - NCI-H295, a human adrenocarcinoma cell line, has been proposed as a model system
      to define the role of the renin-angiotensin system in the regulation of
      aldosterone production in humans. Because the precise cellular localization of
      the components of the renin-angiotensin system in human adrenal cortical cells
      remains unclear, we investigated their localization in this defined cell system.
      NCI-H295 cells expressed both angiotensinogen and renin as shown by reverse
      transcriptase polymerase chain reaction and immunohistochemistry. Human
      angiotensin-converting enzyme (ACE) was not detectable by immunocytochemistry,
      ACE binding, or reverse transcriptase polymerase chain reaction. However, 3.5
      mmol/L K+ stimulated the formation of both angiotensin I and angiotensin II 1. 9-
      and 2.5-fold, respectively, and increased aldosterone release 3. 0-fold. The K+
      induced stimulation of aldosterone release was decreased by captopril and
      enalaprilat (24% and 26%, respectively) and by the angiotensin type 1 (AT1)
      receptor antagonist losartan (28%). Angiotensin II-induced stimulation of
      aldosterone release was abolished by losartan treatment. Specific [125I]Sar1
      angiotensin II binding was detected by receptor autoradiography. The binding of
      [125I]Sar1-angiotensin II was completely displaced by the AT1 antagonist losartan
      but not by the AT2 receptor ligand PD 123319, confirming the expression of
      angiotensin II AT1 receptors in NCI-H295 cells. Our results demonstrate that NCI
      H295 cells express most of the components of the renin-angiotensin system. Our
      failure to detect ACE, however, suggests that the production of angiotensin II in
      NCI-H295 cells may be ACE independent. NCI-H295 cells are able to produce
      angiotensin II, and K+ increases aldosterone secretion in part through an
      angiotensin-mediated pathway. The production of angiotensin II in NCI-H295 cells
      demonstrates that this human cell line can be useful to characterize the role of
      locally produced angiotensin II in the regulation of aldosterone release.

PMID- 10205243
TI  - Epithelial sodium channel activity is not increased in hypertension in whites.
AB  - Abnormal renal sodium transport causing excess reabsorption of sodium may be one
      mechanism that causes high blood pressure. For example, increased activity of
      epithelial sodium channels in the distal tubule is the cause of high blood
      pressure in Liddle's syndrome, a rare familial form of hypertension. We have
      shown that the increase in sodium channel activity can be detected in the nose
      using transepithelial potential difference measurements in 1 family with Liddle's
      syndrome. We therefore used nasal potential difference measurements to look for
      increased sodium channel activity in white patients with essential hypertension.
      Transnasal potential difference was measured in 42 white hypertensive (HT)
      subjects and 38 white normotensive (NT) subjects before and after topical
      application of 10(-4) mol/L of amiloride. There was no difference in maximum
      potential between HT and NT subjects (HT, -18.8+/-0.9 mV; NT, -18.2+/-1.0 mV)
      (values mean+/-SEM; lumen-negative with respect to the submucosa). However, the
      postamiloride potential was significantly higher (HT, -12.6+/-0.7 mV; NT, -10.5+/
      0.7 mV; P=0. 015) and the change in potential in response to amiloride
      significantly lower (HT, 6.2+/-0.5 mV, 33.1+/-2.0%; NT, 7.7+/-0.6 mV, 41.9+/
      2.0%; P=0.046 and 0.003, respectively) in HT than in NT subjects. These results
      suggest that sodium channel activity is not increased in whites with essential
      hypertension and indicate that sodium channel overactivity similar to that seen
      in Liddle's syndrome is unlikely to be the cause of high blood pressure in this
      group. Increased postamiloride potential may reflect increased activity of
      chloride channels or amiloride-insensitive sodium channels.

PMID- 10205244
TI  - Dopamine-1 receptor coupling defect in renal proximal tubule cells in
      hypertension.
AB  - The ability of the dopamine-1 (D1)-like receptor to stimulate adenylyl cyclase
      (AC) and phospholipase C (PLC), inhibit sodium transport in the renal proximal
      tubule (RPT), and produce natriuresis is attenuated in several rat models of
      hypertension. Since the inhibitory effect of D1-like receptors on RPT sodium
      transport is also reduced in some patients with essential hypertension, we
      measured D1-like receptor coupling to AC and PLC in cultures of human RPT cells
      from normotensive (NT) and hypertensive (HT) subjects. Basal cAMP concentrations
      were the same in NT (n=6) and HT (n=4). However, the D1-like receptor agonist
      fenoldopam increased cAMP production to a greater extent in NT (maximum
      response=67+/-1%) than in HT (maximum response=17+/-5%), with a potency ratio of
      105. Dopamine also increased cAMP production to a greater extent in NT (32+/-3%)
      than in HT (14+/-3%). The fenoldopam-mediated increase in cAMP production was
      blocked by SCH23390 (a D1-like receptor antagonist) and by antisense D1
      oligonucleotides in both HT and NT, indicating action at the D1 receptor. The
      stimulatory effects of forskolin and parathyroid hormone-related protein of cAMP
      accumulation were not statistically different in NT and HT, indicating receptor
      specificity and an intact G-protein/AC pathway. The fenoldopam-stimulated PLC
      activity was not impaired in HT, and the primary sequence and expression of the
      D1 receptor were the same in NT and HT. However, D1 receptor serine
      phosphorylation in the basal state was greater in HT than in NT and was not
      responsive to fenoldopam stimulation in HT. These studies demonstrate the
      expression of D1 receptors in human RPT cells in culture. The uncoupling of the
      D1 receptor in both rats (previously described) and humans (described here)
      suggests that this mechanism may be involved in the pathogenesis of hypertension;
      the uncoupling may be due to ligand-independent phosphorylation of the D1
      receptor in hypertension.

PMID- 10205245
TI  - Inhibition of carbonic anhydrase accounts for the direct vascular effects of
      hydrochlorothiazide.
AB  - Hydrochlorothiazide has been shown to exert direct vasodilator effects by
      activation of calcium-activated potassium (KCa) channels in human and guinea pig
      isolated resistance arteries. Since hydrochlorothiazide binds to and inhibits the
      enzyme carbonic anhydrase and because KCa channel activation is pH sensitive, we
      investigated the role of intracellular and extracellular carbonic anhydrase in
      the vascular effects of thiazide diuretics. Small arteries were isolated from
      guinea pig mesentery and studied by use of a microvascular myograph technique. In
      some experiments, tone and intracellular pH (pHi) were measured simultaneously
      with 2', 7'-bis(2-carboxyethyl)-5(6)'-carboxyfluorescein (BCECF-AM).
      Bendroflumethiazide, a thiazide diuretic with minimal inhibitory effects on
      carbonic anhydrase, had little effect on noradrenaline-induced tone (16+/-8%
      relaxation) compared with hydrochlorothiazide (74+/-12% relaxation). In contrast
      to hydrochlorothiazide, the action of bendroflumethiazide was unaffected by 100
      nmol/L charybdotoxin, a selective blocker of KCa channels. All inhibitors of
      carbonic anhydrase relaxed noradrenaline-induced tone in a concentration
      dependent manner, and this effect was blocked by charybdotoxin.
      Hydrochlorothiazide and the inhibitors of carbonic anhydrase failed to relax tone
      induced by a depolarizing potassium solution. Acetazolamide and
      hydrochlorothiazide increased pHi by 0.27+/-0.07 and 0.21+/-0.04, respectively,
      whereas bendroflumethiazide had a much smaller effect: 0.06+/-0.03. The rise in
      pHi induced by any agent was not inhibited by charybdotoxin. The vasorelaxant
      effect of hydrochlorothiazide is shared by other inhibitors of carbonic
      anhydrase. Inhibitors of carbonic anhydrase, but not bendroflumethiazide, cause
      intracellular alkalinization, which is associated with KCa channel opening. These
      data suggest that the vasodilator effect of thiazide diuretics results primarily
      from inhibition of vascular smooth muscle cell carbonic anhydrase, which results
      in a rise in pHI, leading to KCa channel activation and vasorelaxation.

PMID- 10205246
TI  - G-Protein beta3 subunit C825T variant and ambulatory blood pressure in essential
      hypertension.
AB  - Recent studies have identified a novel polymorphism (C825T) of the gene encoding
      the beta3 subunit of heterotrimeric G proteins (Gbeta3) associated with enhanced
      activation of G proteins, which appears to be more common in hypertensive
      patients. In the present study we examine the relationship between this genetic
      variant and hypertension in 479 white patients with established essential
      hypertension recruited from the hypertension clinic of the Universitatsklinikum
      Benjamin Franklin in Berlin, Germany, and 1000 normotensive gender- and age
      matched controls. All patients were screened for the presence of secondary
      hypertension and were further characterized by ambulatory blood pressure
      measurements performed in 295 treated and 184 untreated patients. Genotype
      distribution for the Gbeta3-C825T genotype in patients (CC=204, CT=224, TT=51)
      was significantly different from that in controls (CC=514, CT=412, TT=74;
      chi2=11.5, P<0.01), and the T allele was associated with an odds ratio of 1.5
      (95% CI, 1.1 to 2.2) versus non-T carriers for the presence of hypertension.
      However, in both the whole group and the untreated subgroup, blood pressure
      levels between the genotypic groups were virtually identical. Furthermore, age of
      onset of hypertension and number of antihypertensive medications (in treated
      patients) were similar between the genotypic groups. Thus, while our data confirm
      the association between the Gbeta3-C825T variant and essential hypertension, they
      do not support the hypothesis that this marker is associated with more severe
      blood pressure in patients with already established hypertension.

PMID- 10205247
TI  - Association of an apolipoprotein B gene marker with essential hypertension.
AB  - We designed an association (retrospective, case control) study aimed at
      evaluating associations between genetic variations of the human apolipoprotein B
      (apoB) gene and clinical diagnosis of essential hypertension. Our approach was to
      compare the distribution of the alleles of a highly polymorphic variable number
      of tandem repeats localized 3' to the human apoB gene, the apoB 3' hypervariable
      region (HVR), in a group of normotensive and a group of hypertensive individuals.
      We collected DNA samples from 437 unrelated nationals (215 normotensives and 222
      hypertensives) from the United Arab Emirates (UAEs), and we determined their apoB
      3' HVR allele and genotype status with a polymerase chain reaction-based assay.
      In the UAE population, we found 18 alleles underlying a total of 51 genotypes.
      The distribution of these alleles was significantly different between
      normotensive and hypertensive UAE nationals. The main peak of the distributions
      occurred at 35 repeats among hypertensives (with a relative frequency of 25.7%
      versus 19.6% in normotensives) and at 37 repeats among normotensives (28.8%
      versus 20.3% in hypertensives). Alleles with 21, 23, 25, 49, and 55 repeats were
      found in hypertensives only (with a combined relative frequency of 7.6%). We
      conclude that variations of the apoB gene, or of a nearby gene, that may be in
      linkage disequilibrium with these alleles play a role in the development of
      essential hypertension in the UAEs.

PMID- 10205248
TI  - Alexithymia: a facet of essential hypertension.
AB  - Two hundred thirty-seven newly diagnosed yet untreated hypertensive men and
      women, 35 to 54 years of age, were compared with an age- and gender-stratified
      random population sample of 146 normotensive men and women to find out whether
      psychological distress symptoms, anger expression, and alexithymia are associated
      with elevated blood pressure and whether the possible associations are
      independent of sodium and alcohol intake, body mass index, and physical fitness.
      The independent attributes of mean arterial pressure were studied by multivariate
      regression analyses after combining the subjects in the hypertensive and control
      groups. Three questionnaires were used: the Brief Symptom Inventory (BSI-37), a
      31-item version of the Spielberger State-Trait Anger Expression Inventory
      (STAXI), and the Toronto Alexithymia Scale (TAS-26). Total scores of the TAS-26
      were higher (P<0.001) in hypertensive men and women than in their normotensive
      control subjects (75.6+/-7.8 vs 64.1+/-9.8 in men and 72.9+/-7.1 vs 57.5+/-11.5
      in women). There were no differences between the study and control groups in
      psychological distress symptoms, including anxiety, depression, and hostility, or
      in anger expression. In multivariate regression analyses, higher age, male
      gender, higher sodium intake, lower physical fitness, and alexithymia were
      independently and highly significantly (P<0.01 for male gender, P<0.0001 for
      other variables) associated with increased blood pressure, explaining altogether
      39.5% of the cross-sectional variation in mean arterial pressure. We conclude
      that alexithymia, that is, poor ability to experience and express emotions, is
      associated with elevated blood pressure independent of sodium and alcohol intake,
      body mass index, and physical fitness.

PMID- 10205249
TI  - Clinical significance and implications of sympathetic activation 

PMID- 10205250
TI  - Cardiovascular consequences of sympathetic hyperactivity.
AB  - The sympathetic nervous system plays an integral role in many aspects of
      cardiovascular homeostasis. However, intermittent or chronic sympathetic
      hyperactivity can also initiate or accelerate cardiovascular pathology and
      provoke clinical events in the presence of cardiovascular disease. Both alpha-
      and beta-receptors mediate these responses. In the case of the heart, alpha- and
      beta- receptors contribute to ventricular arrhythmias and cardiac hypertrophy.
      Moreover, cardiac beta2-receptors mediate not only chronotropic and inotropic
      responses at the postsynaptic level, but also noradrenalin release at the
      presynaptic level. To block the adverse effects of sympathetic hyperactivity
      optimally, one would therefore need both alpha- and nonselective beta-receptor
      blockade. On the other hand, prevention or reversal of sympathetic hyperactivity
      at the central level appears to be an attractive alternative. Alpha2-agonists
      such as clonidine and alpha-methyldopa are clearly effective in this regard but
      are associated with side effects. More recent research indicates that in the
      central nervous systen (CNS) other classes such as dihydropyridines (eg,
      nifedipine) or angiotensin II type 1 receptor blockers (eg, losartan) also can
      decrease elevated sympathetic nerve activity. The therapeutic relevance of these
      CNS effects and differences between lipophilic and hydrophilic compounds provide
      intriguing new avenues for research in disorders such as hypertension and
      congestive heart failure.

PMID- 10205251
TI  - Effects of antihypertensive therapies on the sympathetic nervous system.
AB  - The sympathetic nervous system is a major modulator of cardiovascular function.
      Over the past three decades, numerous studies, using various methodologies, have
      reported the existence of a variety of pre- and postsynaptic sympathetic
      dysfunctions in essential hypertension. Most of these abnormalities facilitate
      sympathetic neurotransmission, resulting in a chronic increase in the sympathetic
      tone and reactivity in a significant proportion of hypertensive patients. Chronic
      sympathetic activation is also associated with major alterations in the balance
      among postsynaptic adrenergic receptors in cardiovascular tissues. Indeed, an
      attenuation of beta-adrenergic function and a potentiation of alpha1-adrenergic
      function has been demonstrated in cardiovascular tissues in hypertensive
      patients, suggesting the development of a sympathetic postsynaptic alpha1
      dominance during the development and evolution of hypertension. Chronic
      activation of the sympathetic system is deleterious and could contribute to the
      development of most cardiovascular complications associated with hypertension.
      One of the major aims of antihypertensive therapy should thus be to attenuate pre
      or postsynaptic sympathetic tone. Most antihypertensive drugs have been found to
      improve either pre- or postsynaptic sympathetic function in hypertensive
      patients. At the presynaptic level, diuretics were found to increase the
      liberation of noradrenalin, presumably through baroreflex sympathetic activation.
      In contrast, beta-blockers were shown to attenuate noradrenalin release from
      sympathetic nerves by blocking presynaptic facilitatory beta-receptors, thus
      reducing the sympathetic tone on postsynaptic receptors. Similarly, angiotensin
      converting enzyme inhibitors or angiotensin II type 1 (AT1) receptor antagonists
      have been found to reduce sympathetic reactivity by acting on the central nervous
      system, but also by blocking AT1-mediated facilitatory mechanisms located on
      sympathetic fibres and in the adrenal medulla. Short acting dihydropyridine
      calcium channel blockers (CCBs) were found to enhance noradrenalin release from
      sympathetic nerves, but longer acting CCBs seems to have variable effects.
      Indeed, while the chronic slow release formulation of nifedipine gastrointestinal
      therapeutic system (GITS) did not raise circulating noradrenalin levels,
      treatment with amlodipine increased circulating noradrenalin levels, suggesting
      that nifedipine GITS is neutral on the sympathetic tone but that amlodipine
      chronically activates the sympathetic system. At the postsynaptic level, however,
      dihydropyridine CCBs were shown to attenuate the sympathetic tone on alpha1
      adrenoceptors. In conclusion, it appears that most antihypertensive drugs
      interfere with pre- or postsynaptic sympathetic mechanisms and that these
      mechanisms could contribute to their hypotensive effects.

PMID- 10205252
TI  - The relevance of sympathetic activity in the pharmacological treatment of chronic
      stable angina.
AB  - A large body of evidence suggests that persistently high heart rate may be
      associated with a significant increase in sudden death, myocardial infarction and
      total mortality. Such deleterious effects may be mediated via neurohumoral
      activation. Conversely, interventions, such as beta-blockers, that consistently
      reduce heart rate may reduce sudden death and prolong survival, especially in
      patients who survive myocardial infarction. Thus, the deleterious effect of
      antianginal compounds, which may increase heart rate, is especially important in
      chronic myocardial syndromes as well as in chronic stable angina. In this
      setting, the evidence is consistent with the belief that antianginal agents that
      increase heart rate significantly, irrespective of their other properties, may
      also increase the incidence of myocardial infarction or death, in contrast to
      agents that induce little or no tachycardic effect or those that produce frankly
      bradycardic responses. Data discussed in this paper indicate that long acting
      calcium channel blockers of the dihydropyridine type do not increase heart rate
      significantly. Their slower onset and offset of action may reflect a lack of
      neurohumoral activation, recently confirmed in the case of nifedipine
      gastrointestinal therapeutic system (GITS). Data from the Nifedipine
      gastrointestinal therapeutic system Circadian Antiischemic Program (N-CAP) study,
      summarized herein, confirmed that the GITS formulation produces a minimal
      increase in heart rate over a period of 24 h. When the compound was given alone
      or with a beta-blocker, it was highly effective in suppressing symptomatic and
      asymptomatic episodes of myocardial ischemia in patients with chronic stable
      angina. These findings have important implications for the treatment of ischemia
      in patients with chronic stable angina.

PMID- 10205253
TI  - Hypertension in the elderly: a patient case study.

PMID- 10205254
TI  - Transcription-coupled repair of DNA damage: unanticipated players, unexpected
      complexities.

PMID- 10205255
TI  - The mammalian Mre11-Rad50-nbs1 protein complex: integration of functions in the
      cellular DNA-damage response.

PMID- 10205256
TI  - Immunoglobulin class switch recombination: will genetics provide new clues to
      mechanism?

PMID- 10205257
TI  - Repair of mtDNA in vertebrates.

PMID- 10205258
TI  - Poly(ADP-ribose) polymerase in the cellular response to DNA damage, apoptosis,
      and disease.

PMID- 10205259
TI  - Outrageous fortune: the risk of suicide in genetic testing for Huntington
      disease.

PMID- 10205261
TI  - Comprehensive mutation analysis of TSC1 and TSC2-and phenotypic correlations in
      150 families with tuberous sclerosis.
AB  - Tuberous sclerosis (TSC [MIM 191090 and MIM 191100]) is an autosomal dominant
      disorder characterized by hamartomas in many organs. Two thirds of cases are
      sporadic and are thought to represent new mutations. TSC is caused by mutations
      affecting either of the presumed tumor-suppressor genes, TSC1 and TSC2. Both
      appear to function as tumor suppressors, because somatic loss or intragenic
      mutation of the corresponding wild-type allele is seen in the associated
      hamartomas. Here we report the first comprehensive mutation analysis of TSC1 and
      TSC2 in a cohort of 150 unrelated TSC patients and their families, using
      heteroduplex and SSCP analysis of all coding exons and using pulsed-field gel
      electrophoresis and conventional Southern blot analysis and long PCR to screen
      for large rearrangements. Mutations were characterized in 120 (80%) of the 150
      cases, affecting TSC1 in 22 cases and TSC2 in 98 cases. TSC1 mutations were
      significantly underrepresented in sporadic cases (P=. 000185). Twenty-two
      patients had TSC2 missense mutations that were found predominantly in the GAP
      related domain (eight cases) and in a small region encoded in exons 16 and 17,
      between nucleotides 1849 and 1859 (eight cases), consistent with the presence of
      residues performing key functions at these sites. In contrast, all TSC1 mutations
      were predicted to be truncating, consistent with a structural or adapter role for
      the encoded protein. Intellectual disability was significantly more frequent in
      TSC2 sporadic cases than in TSC1 sporadic cases (P=.0145). These data provide the
      first representative picture of the distribution and spectrum of mutations across
      the TSC1 and TSC2 loci in clinically ascertained TSC and support a difference in
      severity of TSC1- and TSC2-associated disease.

PMID- 10205262
TI  - Analysis of alkaptonuria (AKU) mutations and polymorphisms reveals that the CCC
      sequence motif is a mutational hot spot in the homogentisate 1,2 dioxygenase gene
      (HGO).
AB  - We recently showed that alkaptonuria (AKU) is caused by loss-of-function
      mutations in the homogentisate 1,2 dioxygenase gene (HGO). Herein we describe
      haplotype and mutational analyses of HGO in seven new AKU pedigrees. These
      analyses identified two novel single-nucleotide polymorphisms (INV4+31A-->G and
      INV11+18A-->G) and six novel AKU mutations (INV1-1G-->A, W60G, Y62C, A122D,
      P230T, and D291E), which further illustrates the remarkable allelic heterogeneity
      found in AKU. Reexamination of all 29 mutations and polymorphisms thus far
      described in HGO shows that these nucleotide changes are not randomly
      distributed; the CCC sequence motif and its inverted complement, GGG, are
      preferentially mutated. These analyses also demonstrated that the nucleotide
      substitutions in HGO do not involve CpG dinucleotides, which illustrates
      important differences between HGO and other genes for the occurrence of mutation
      at specific short-sequence motifs. Because the CCC sequence motifs comprise a
      significant proportion (34.5%) of all mutated bases that have been observed in
      HGO, we conclude that the CCC triplet is a mutational hot spot in HGO.

PMID- 10205260
TI  - A worldwide assessment of the frequency of suicide, suicide attempts, or
      psychiatric hospitalization after predictive testing for Huntington disease.
AB  - Prior to the implementation of predictive-testing programs for Huntington disease
      (HD), significant concern was raised concerning the likelihood of catastrophic
      events (CEs), particularly in those persons receiving an increased-risk result.
      We have investigated the frequency of CEs-that is, suicide, suicide attempt, and
      psychiatric hospitalization-after an HD predictive-testing result, through
      questionnaires sent to predictive-testing centers worldwide. A total of 44
      persons (0.97%) in a cohort of 4,527 test participants had a CE: 5 successful
      suicides, 21 suicide attempts, and 18 hospitalizations for psychiatric reasons.
      All persons committing suicide had signs of HD, whereas 11 (52.4%) of 21 persons
      attempting suicide and 8 (44.4%) of 18 who had a psychiatric hospitalization were
      symptomatic. A total of 11 (84.6%) of 13 asymptomatic persons who experienced a
      CE during the first year after HD predictive testing received an increased-risk
      result. Factors associated with an increased risk of a CE included (a) a
      psychiatric history </=5 years prior to testing and (b) unemployed status. The
      frequency of CEs did not differ between those persons receiving results of
      predictive testing through linkage analysis in whom there was only changes in
      direction of risk and those persons receiving definitive results after analysis
      for the mutation underlying HD. These findings provide insights into the
      frequency, associated factors, and timing of CEs in a worldwide cohort of persons
      receiving predictive-testing results and, as such, highlight persons for whom
      ongoing support may be beneficial.

PMID- 10205263
TI  - Identification of a genetic defect in the hairless gene in atrichia with papular
      lesions: evidence for phenotypic heterogeneity among inherited atrichias.
AB  - Recently, we showed that atrichia with papular lesions (APL), a rare inherited
      form of alopecia, is transmitted as an autosomal recessive trait in a large
      inbred kindred of Israeli-Arab origin. Furthermore, we mapped the APL locus to a
      5-cM region of chromosome 8p12 in this family. The human "hairless" gene is a
      candidate target gene for the disease mutation because it maps to the APL locus
      and because it was recently found to be mutated in a related but clinically
      distinct form of alopecia known as "alopecia universalis" or "congenital
      alopecia." In the present study, the coding sequence of the hairless gene was
      compared by reverse transcription-PCR in fibroblast cell lines derived from an
      affected patient and an unrelated individual. We identified a single-base
      deletion (3434delC) in the hairless gene that cosegregated with the disease
      phenotype in the family. This deletion is predicted to cause a frameshift
      mutation in the highly conserved C-terminal part of the hairless protein, a
      region putatively involved in the transcription factor activity of the hairless
      gene product. The present results are indicative of phenotypic heterogeneity in
      inherited atrichias caused by mutations in the hairless gene, suggesting
      different roles for the regions mutated in APL and in other forms of congenital
      atrichia during hair development.

PMID- 10205265
TI  - Quantitative analysis of survival motor neuron copies: identification of subtle
      SMN1 mutations in patients with spinal muscular atrophy, genotype-phenotype
      correlation, and implications for genetic counseling.
AB  - Problems with diagnosis and genetic counseling occur for patients with autosomal
      recessive proximal spinal muscular atrophy (SMA) who do not show the most common
      mutation: homozygous absence of at least exon 7 of the telomeric survival motor
      neuron gene (SMN1). Here we present molecular genetic data for 42 independent
      nondeleted SMA patients. A nonradioactive quantitative PCR test showed one SMN1
      copy in 19 patients (45%). By sequencing cloned reverse-transcription (RT) PCR
      products or genomic fragments of SMN1, we identified nine different mutations in
      18 of the 19 patients, six described for the first time: three missense mutations
      (Y272C, T274I, S262I), three frameshift mutations in exons 2a, 2b, and 4
      (124insT, 241-242ins4, 591delA), one nonsense mutation in exon 1 (Q15X), one Alu
      mediated deletion from intron 4 to intron 6, and one donor splice site mutation
      in intron 7 (c.922+6T-->G). The most frequent mutation, Y272C, was found in 6
      (33%) of 18 patients. Each intragenic mutation found in at least two patients
      occurred on the same haplotype background, indicating founder mutations. Genotype
      phenotype correlation allowed inference of the effect of each mutation on the
      function of the SMN1 protein and the role of the SMN2 copy number in modulating
      the SMA phenotype. In 14 of 23 SMA patients with two SMN1 copies, at least one
      intact SMN1 copy was sequenced, which excludes a 5q-SMA and suggests the
      existence of further gene(s) responsible for approximately 4%-5% of phenotypes
      indistinguishable from SMA. We determined the validity of the test, and we
      discuss its practical implications and limitations.

PMID- 10205264
TI  - An mtDNA mutation in the initiation codon of the cytochrome C oxidase subunit II
      gene results in lower levels of the protein and a mitochondrial
      encephalomyopathy.
AB  - A novel heteroplasmic 7587T-->C mutation in the mitochondrial genome which
      changes the initiation codon of the gene encoding cytochrome c oxidase subunit II
      (COX II), was found in a family with mitochondrial disease. This T-->C transition
      is predicted to change the initiating methionine to threonine. The mutation load
      was present at 67% in muscle from the index case and at 91% in muscle from the
      patient's clinically affected son. Muscle biopsy samples revealed isolated COX
      deficiency and mitochondrial proliferation. Single-muscle-fiber analysis revealed
      that the 7587C copy was at much higher load in COX-negative fibers than in COX
      positive fibers. After microphotometric enzyme analysis, the mutation was shown
      to cause a decrease in COX activity when the mutant load was >55%-65%. In
      fibroblasts from one family member, which contained >95% mutated mtDNA, there was
      no detectable synthesis or any steady-state level of COX II. This new mutation
      constitutes a new mechanism by which mtDNA mutations can cause disease-defective
      initiation of translation.

PMID- 10205266
TI  - Connexin46 mutations in autosomal dominant congenital cataract.
AB  - Loci for autosomal dominant "zonular pulverulent" cataract have been mapped to
      chromosomes 1q (CZP1) and 13q (CZP3). Here we report genetic refinement of the
      CZP3 locus and identify underlying mutations in the gene for gap-junction protein
      alpha-3 (GJA3), or connexin46 (Cx46). Linkage analysis gave a significantly
      positive two-point LOD score (Z) at marker D13S175 (maximum Z [Zmax]=>7.0;
      maximum recombination frequency [thetamax] =0). Haplotyping indicated that CZP3
      probably lies in the genetic interval D13S1236-D13S175-D13S1316-cen-13pter, close
      to GJA3. Sequencing of a genomic clone isolated from the CZP3 candidate region
      identified an open reading frame coding for a protein of 435 amino acids (47,435
      D) that shared approximately 88% homology with rat Cx46. Mutation analysis of
      GJA3 in two families with CZP3 detected distinct sequence changes that were not
      present in a panel of 105 normal, unrelated individuals. In family B, an A-->G
      transition resulted in an asparagine-to-serine substitution at codon 63 (N63S)
      and introduced a novel MwoI restriction site. In family E, insertion of a C at
      nucleotide 1137 (1137insC) introduced a novel BstXI site, causing a frameshift at
      codon 380. Restriction analysis confirmed that the novel MwoI and BstXI sites
      cosegregated with the disease in families B and E, respectively. This study
      identifies GJA3 as the sixth member of the connexin gene family to be implicated
      in human disease, and it highlights the physiological importance of gap-junction
      communication in the development of a transparent eye lens.

PMID- 10205267
TI  - The promoters of the survival motor neuron gene (SMN) and its copy (SMNc) share
      common regulatory elements.
AB  - Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular
      disorder characterized by degeneration of motor neurons of the spinal cord. The
      survival motor neuron gene (SMN) has been recognized as the disease-causing gene.
      SMN is duplicated, and the almost identical copy gene (SMNc) remains functional
      in patients with SMA. The expression level of SMNc is tightly correlated with the
      clinical severity of the disease. Here, we define the transcription initiation
      site, delineate the region containing promoter activity, and analyze the sequence
      of the promoter region of both SMN and SMNc. We show that the promoter sequence
      and activity of the two genes are quasi identical, providing strong evidence for
      similar transcription regulation of the two genes. Therefore, the difference in
      the level of protein encoded by SMN and SMNc is the result of either different
      regulatory region(s) further apart or different posttranscriptional regulation.
      Interestingly, sequence analysis of the promoter region revealed several
      consensus binding sites for transcription factors. Therefore, the identification
      of transcription factors involved in the regulation of SMNc gene expression may
      lead to attractive strategies for therapy in SMA.

PMID- 10205268
TI  - Modification of BRCA1-associated breast cancer risk by the polymorphic androgen
      receptor CAG repeat.
AB  - Compared with the general population, women who have inherited a germline
      mutation in the BRCA1 gene have a greatly increased risk of developing breast
      cancer. However, there is also substantial interindividual variability in the
      occurrence of breast cancer among BRCA1 mutation carriers. We hypothesize that
      other genes, particularly those involved in endocrine signaling, may modify the
      BRCA1-associated age-specific breast cancer risk. We studied the effect of the
      CAG repeat-length polymorphism found in exon 1 of the androgen-receptor (AR) gene
      (AR-CAG). AR alleles containing longer CAG repeat lengths are associated with a
      decreased ability to activate androgen-responsive genes. Using a sample of women
      who inherited germline BRCA1 mutations, we compared AR-CAG repeat length in 165
      women with and 139 women without breast cancer. We found that women were at
      significantly increased risk of breast cancer if they carried at least one AR
      allele with >/=28 CAG repeats. Women who carried an AR-CAG allele of >/=28,
      >/=29, or >/=30 repeats were given a diagnosis 0.8, 1.8, or 6.3 years earlier
      than women who did not carry at least one such allele. All 11 women in our sample
      who carried at least one AR-CAG allele with >/=29 repeats had breast cancer. Our
      results support the hypothesis that age at breast cancer diagnosis is earlier
      among BRCA1 mutation carriers who carry very long AR-CAG repeats. These results
      suggest that pathways involving androgen signaling may affect the risk of BRCA1
      associated breast cancer.

PMID- 10205269
TI  - A third major locus for autosomal dominant hypercholesterolemia maps to 1p34.1
      p32.
AB  - Autosomal dominant hypercholesterolemia (ADH), one of the most frequent
      hereditary disorders, is characterized by an isolated elevation of LDL particles
      that leads to premature mortality from cardiovascular complications. It is
      generally assumed that mutations in the LDLR and APOB genes account for ADH. We
      identified one large French pedigree (HC2) and 12 additional white families with
      ADH in which we excluded linkage to the LDLR and APOB, implicating a new locus we
      named "FH3." A LOD score of 3.13 at a recombination fraction of 0 was obtained at
      markers D1S2892 and D1S2722. We localized the FH3 locus to a 9-cM interval at
      1p34.1-p32. We tested four regional markers in another set of 12 ADH families.
      Positive LOD scores were obtained in three pedigrees, whereas linkage was
      excluded in the others. Heterogeneity tests indicated linkage to FH3 in
      approximately 27% of these non-LDLR/non-APOB ADH families and implied a fourth
      locus. Radiation hybrid mapping located four candidate genes at 1p34.1-p32,
      outside the critical region, showing no identity with FH3. Our results show that
      ADH is genetically more heterogeneous than conventionally accepted.

PMID- 10205270
TI  - Juvenile hemochromatosis locus maps to chromosome 1q.
AB  - Juvenile hemochromatosis (JH) is an autosomal recessive disorder that leads to
      severe iron loading in the 2d to 3d decade of life. Affected members in families
      with JH do not show linkage to chromosome 6p and do not have mutations in the HFE
      gene that lead to the common hereditary hemochromatosis. In this study we
      performed a genomewide search to map the JH locus in nine families: six
      consanguineous and three with multiple affected patients. This strategy allowed
      us to identify the JH locus on the long arm of chromosome 1. A maximum LOD score
      of 5.75 at a recombination fraction of 0 was detected with marker D1S498, and a
      LOD score of 5. 16 at a recombination fraction of 0 was detected for marker
      D1S2344. Homozygosity mapping in consanguineous families defined the limits of
      the candidate region in an approximately 4-cM interval between markers D1S442 and
      D1S2347. Analysis of genes mapped in this interval excluded obvious candidates.
      The JH locus does not correspond to the chromosomal localization of any known
      gene involved in iron metabolism. These findings provide a means to recognize, at
      an early age, patients in affected families. They also provide a starting point
      for the identification of the affected gene by positional cloning.

PMID- 10205271
TI  - A new locus for autosomal dominant stargardt-like disease maps to chromosome 4.
AB  - Stargardt disease (STGD) is the most common hereditary macular dystrophy and is
      characterized by decreased central vision, atrophy of the macula and underlying
      retinal-pigment epithelium, and frequent presence of prominent flecks in the
      posterior pole of the retina. STGD is most commonly inherited as an autosomal
      recessive trait, but many families have been described in which features of the
      disease are transmitted in an autosomal dominant manner. A recessive locus has
      been identified on chromosome 1p (STGD1), and dominant loci have been mapped to
      both chromosome 13q (STGD2) and chromosome 6q (STGD3). In this study, we describe
      a kindred with an autosomal dominant Stargardt-like phenotype. A genomewide
      search demonstrated linkage to a locus on chromosome 4p, with a maximum LOD score
      of 5.12 at a recombination fraction of.00, for marker D4S403. Analysis of
      extended haplotypes localized the disease gene to an approximately 12-cM interval
      between loci D4S1582 and D4S2397. Therefore, this kindred establishes a new
      dominant Stargardt-like locus, STGD4.

PMID- 10205272
TI  - The Fanconi anemia group E gene, FANCE, maps to chromosome 6p.
AB  - Fanconi anemia (FA) is a genetically heterogeneous autosomal recessive disease
      with bone marrow failure and predisposition to cancer as major features, often
      accompanied by developmental anomalies. The cells of patients with FA are
      hypersensitive to DNA cross-linking agents in terms of cell survival and
      chromosomal breakage. Of the eight complementation groups (FA-A to FA-H)
      distinguished thus far by cell fusion studies, the genes for three-FANCA, FANCC,
      and FANCG-have been identified, and the FANCD gene has been localized to
      chromosome 3p22-26. We report here the use of homozygosity mapping and genetic
      linkage analysis to map a fifth distinct genetic locus for FA. DNA from three
      families was assigned to group FA-E by cell fusion and complementation analysis
      and was then used to localize the FANCE gene to chromosome 6p21-22 in an 18.2-cM
      region flanked by markers D6S422 and D6S1610. This study shows that data from
      even a small number of families can be successfully used to map a gene for a
      genetically heterogeneous disorder.

PMID- 10205273
TI  - The critical region for Behcet disease in the human major histocompatibility
      complex is reduced to a 46-kb segment centromeric of HLA-B, by association
      analysis using refined microsatellite mapping.
AB  - The HLA-B51 allele is known to be associated with Behcet disease. Recently, we
      found a higher risk for Behcet disease in the MICA gene, 46 kb centromeric of HLA
      B, by investigation of GCT repetitive polymorphism within exon 5 of MICA. The
      pathogenic gene causing Behcet disease, however, has remained uncertain. Here,
      eight polymorphic microsatellite markers, distributed over a 900-kb region
      surrounding the HLA-B locus, were subjected to association analysis for Behcet
      disease. Statistical studies of associated alleles detected on each
      microsatellite locus showed that the pathogenic gene for Behcet disease is most
      likely found within a 46-kb segment between the MICA and HLA-B genes. The results
      of this mapping study, and the results of an earlier study of ours, suggest that
      MICA is a strong candidate gene for the development of Behcet disease.

PMID- 10205274
TI  - Evidence for linkage of adolescent-onset idiopathic generalized epilepsies to
      chromosome 8-and genetic heterogeneity.
AB  - Several loci and candidate genes for epilepsies or epileptic syndromes map or
      have been suggested to map to chromosome 8. We investigated families with
      adolescent-onset idiopathic generalized epilepsy (IGE), for linkage to markers
      spanning chromosome 8. The IGEs that we studied included juvenile myoclonic
      epilepsy (JME), epilepsy with only generalized tonic-clonic seizures occurring
      either randomly during the day (random grand mal) or on awakening (awakening
      grand mal), and juvenile absence epilepsy (JAE). We looked for a gene common to
      all these IGEs, but we also investigated linkage to specific subforms of IGE. We
      found evidence for linkage to chromosome 8 in adolescent-onset IGE families in
      which JME was not present. The maximum multipoint LOD score was 3.24 when family
      members with IGE or generalized spike-and-waves (SW) were considered affected.
      The LOD score remained very similar (3.18) when clinically normal family members
      with SW were not considered to be affected. Families with either pure grand mal
      epilepsy or absence epilepsy contributed equally to the positive LOD score. The
      area where the LOD score reaches the maximum encompasses the location of the gene
      for the beta3-subunit of the nicotinic acetylcholine receptor (CHRNB3), thus
      making this gene a possible candidate for these specific forms of adolescent
      onset IGE. The data excluded linkage of JME to this region. These results
      indicate genetic heterogeneity within IGE and provide no evidence, on chromosome
      8, for a gene common to all IGEs.

PMID- 10205275
TI  - Dominant hereditary inclusion-body myopathy gene (IBM3) maps to chromosome region
      17p13.1.
AB  - We recently described an autosomal dominant inclusion-body myopathy characterized
      by congenital joint contractures, external ophthalmoplegia, and predominantly
      proximal muscle weakness. A whole-genome scan, performed with 161 polymorphic
      markers and with DNA from 40 members of one family, indicated strong linkage for
      markers on chromosome 17p. After analyses with additional markers in the region
      and with DNA from eight additional family members, a maximum LOD score (Zmax) was
      detected for marker D17S1303 (Zmax=7.38; recombination fraction (theta)=0).
      Haplotype analyses showed that the locus (Genome Database locus name: IBM3) is
      flanked distally by marker D17S945 and proximally by marker D17S969. The
      positions of cytogenetically localized flanking markers suggest that the location
      of the IBM3 gene is in chromosome region 17p13.1. Radiation hybrid mapping showed
      that IBM3 is located in a 2-Mb chromosomal region and that the myosin heavy-chain
      (MHC) gene cluster, consisting of at least six genes, co-localizes to the same
      region. This localization raises the possibility that one of the MHC genes
      clustered in this region may be involved in this disorder.

PMID- 10205277
TI  - Transmission of a fully functional human neocentromere through three generations.
AB  - An unusual Y chromosome with a primary constriction inside the long-arm
      heterochromatin was found in the amniocytes of a 38-year-old woman. The same Y
      chromosome was found in her husband and brother-in-law, thus proving that it was
      already present in the father. FISH with alphoid DNA showed hybridization signals
      at the usual position of the Y centromere but not at the primary constriction.
      Centromere proteins (CENP)-A, CENP-C, and CENP-E could not be detected at the
      site of the canonic centromere but were present at the new constriction, whereas
      CENP-B was not detected on this Y chromosome. Experiments with 82 Y-specific loci
      distributed throughout the chromosome confirmed that no gross deletion or
      rearrangement had taken place, and that the Y chromosome belonged to a haplogroup
      whose members have a mean alphoid array of 770 kb (range 430-1,600 kb), whereas
      that of this case was approximately 250 kb. Thus, this Y chromosome appeared to
      be deleted for part of the alphoid DNA. It seems likely that this deletion was
      responsible for the silencing of the normal centromere and that the activation of
      the neocentromere prevented the loss of this chromosome. Alternatively,
      neocentromere activation could have occurred first and stimulated inactivation of
      the normal centromere by partial deletion. Whatever the mechanism, the presence
      of this chromosome in three generations demonstrates that it functions
      sufficiently well in mitosis for male sex determination and fertility and that
      neocentromeres can be transmitted normally at meiosis.

PMID- 10205276
TI  - Evidence for effective suppression of recombination in the chromosome 17q21
      segment spanning RNU2-BRCA1.
AB  - Characterization of associations between polymorphic sites located throughout the
      approximately 200-400-kb variable-length region spanning RNU2-BRCA1 reveals
      nearly complete linkage disequilibrium. This segment spans the RNU2 array, which
      includes 6-30 tandem copies of the U2 snRNA gene, and an adjacent region
      containing NBR1, the LBRCA1 pseudogene, NBR2, and BRCA1 in a tandemly duplicated
      structure. A series of biallelic polymorphisms define two common haplotypes that
      do not vary significantly, in structure or frequency, between populations of
      primarily European (n=275) or Asian (n=34) ancestry. Lower-frequency variants
      occurring at distantly located sites within this region also show very strong
      associations. The rarer haplotype classes appear to be distinguished by
      mutational alteration and are not recombination products of the two major
      classes. The two major haplotypes also exhibit significantly different allele
      length distributions for local simple tandem-repeat markers. The conservation of
      extensive distinct chromosomal haplotypes during a long period of human
      population expansion and divergence indicates that selective forces or specific
      chromosomal mechanisms result in effective recombination suppression. The extreme
      degree of long-range linkage disequilibrium at this locus may be exceeded only by
      that reported for the human MHC locus, where allele-specific functional
      interactions are believed to be significant. These findings have implications for
      the estimation of the time of origin of BRCA1 mutations having a founder effect,
      the interpretation of the significance of rare allelic variants, and the study of
      the origins of modern populations.

PMID- 10205278
TI  - Heterogeneous X inactivation in trophoblastic cells of human full-term female
      placentas.
AB  - In female mammalian cells, one of the two X chromosomes is inactivated to
      compensate for gene-dose effects, which would be otherwise doubled compared with
      that in male cells. In somatic lineages in mice, the inactive X chromosome can be
      of either paternal or maternal origin, whereas the paternal X chromosome is
      specifically inactivated in placental tissue. In human somatic cells, X
      inactivation is mainly random, but both random and preferential paternal X
      inactivation have been reported in placental tissue. To shed more light on this
      issue, we used PCR to study the methylation status of the polymorphic androgen
      receptor gene in full-term human female placentas. The sites investigated are
      specifically methylated on the inactive X chromosome. No methylation was found in
      microdissected stromal tissue, whether from placenta or umbilical cord. Of nine
      placentas for which two closely apposed samples were studied, X inactivation was
      preferentially maternal in three, was preferentially paternal in one, and was
      heterogeneous in the remaining five. Detailed investigation of two additional
      placentas demonstrated regions with balanced (1:1 ratio) preferentially maternal
      and preferentially paternal X inactivation. No differences in ratio were observed
      in samples microdissected to separate trophoblast and stromal tissues. We
      conclude that methylation of the androgen receptor in human full-term placenta is
      specific for trophoblastic cells and that the X chromosome can be of either
      paternal or maternal origin.

PMID- 10205280
TI  - Relationship estimation by Markov-process models in a sib-pair linkage study.
AB  - The results of sib-pair linkage studies may be compromised if a substantial
      number of putative sib pairs are not actually sib pairs. For classification of
      pairs in a sib-pair genome scan, I propose multipoint methods that are based on a
      Markov-process model of allele sharing along the chromosome. These methods can be
      implemented by standard algorithms that compute multipoint marker allele-sharing
      probabilities for sib pairs. When marker data from at least half the genome are
      used, misclassification rates are small. The methods will be implemented in an
      upcoming version of the computer software package S.A.G.E.

PMID- 10205281
TI  - Mutation rate in human microsatellites.

PMID- 10205279
TI  - Genomewide scan for familial combined hyperlipidemia genes in finnish families,
      suggesting multiple susceptibility loci influencing triglyceride, cholesterol,
      and apolipoprotein B levels.
AB  - Familial combined hyperlipidemia (FCHL) is a common dyslipidemia predisposing to
      premature coronary heart disease (CHD). The disease is characterized by increased
      levels of serum total cholesterol (TC), triglycerides (TGs), or both. We recently
      localized the first locus for FCHL, on chromosome 1q21-q23. In the present study,
      a genomewide screen for additional FCHL loci was performed. In stage 1, we
      genotyped 368 polymorphic markers in 35 carefully characterized Finnish FCHL
      families. We identified six chromosomal regions with markers showing LOD score
      (Z) values >1.0, by using a dominant mode of inheritance for the FCHL trait. In
      addition, two more regions emerged showing Z>2.0 with a TG trait. In stage 2, we
      genotyped 26 more markers and seven additional FCHL families for these
      interesting regions. Two chromosomal regions revealed Z>2.0 in the linkage
      analysis: 10p11.2, Z=3.20 (theta=.00), with the TG trait; and 21q21, Z=2.24
      (theta=.10), with the apoB trait. Furthermore, two more chromosomal regions
      produced Z>2.0 in the affected-sib-pair analysis: 10q11.2-10qter produced Z=2.59
      with the TC trait and Z=2.29 with FCHL, and 2q31 produced Z=2.25 with the TG
      trait. Our results suggest additional putative loci influencing FCHL in Finnish
      families, some potentially affecting TG levels and some potentially affecting TC
      or apoB levels.

PMID- 10205282
TI  - Recurrent Williams-Beuren syndrome in a sibship suggestive of maternal germ-line
      mosaicism.

PMID- 10205283
TI  - Localization of a gene for bitter-taste perception to human chromosome 5p15.

PMID- 10205284
TI  - Sperm chromosome analysis in a man heterozygous for a paracentric inversion of
      chromosome 14 (q24.1q32.1)

PMID- 10205285
TI  - A program for the monte carlo evaluation of significance of the extended
      transmission/disequilibrium test.

PMID- 10205286
TI  - Genomewide Transmission/Disequilibrium testing: a correction.

PMID- 10205287
TI  - Pneumocystis carinii pneumonia in the Federal Republic of Germany in the era of
      changing antiretroviral therapy - IDKF 13 -. German AIDS Study Group (GASG/IdKF).
AB  - BACKGROUND: Pneumocystis carinii pneumonia (PCP) is one of the most common AIDS
      defining diagnoses. METHODS: In a prospective observational trial all cases of
      Pneumocystis carinii pneumonia (PCP) were evaluated. Patients with and without
      PCP-prophylaxis were compared for symptoms, efficacy, side effects and mortality
      at week 4 and 26. RESULTS: 293 patients developed a PCP episode. Patients with no
      prophylaxis had a significant lower CD4 cell count and a more severe clinical
      status at time of diagnosis. This was pronounced in the group with first positive
      HIV test at time of diagnosis. There was no difference in the rate of successful
      treatment between both groups. At week four a tendency to a better survival in
      the group with prophylaxis was observed, however this changed to a trend to a
      better survival at week 26 for the group without prophylaxis. CONCLUSION: Even in
      the era of highly active antiretroviral treatment many patients present with PCP.
      Nearly 60% of patients presented without antiretroviral treatment or PCP
      prophylaxis. Nearly 25% of all patients had their first HIV-test at time of PCP
      diagnosis.

PMID- 10205289
TI  - Tumour markers - new aspects of an old discussion?
AB  - The knowledge about the molecular genetic features of cancer has been vastly
      increased within the last few years. Tumor markers used so far for diagnosis,
      monitoring, and follow-up of cancer patients are tumor-associated rather than
      tumor-specific. Therefore, the development of more sensitive and specific tumor
      markers is urgently needed. In this review, the possibilities of using molecular
      genetic characteristics of cancer as specific and sensitive tumor markers are
      discussed.

PMID- 10205288
TI  - Effects of HMG-CoA reductase inhibition on PDGF- and angiotensin II- mediated
      signal transduction: suppression of c-Jun and c-Fos in human smooth muscle cells
      in vitro.
AB  - Hydroxymethylglutaryl-Coenzyme A (HMG-CoA) reductase inhibitors were shown to be
      effective in primary and secondary prevention of coronary heart disease. The
      beneficial effect of statins is generally attributed to their cholesterol
      lowering activity. However recent work points to additional cholesterol
      independent effects of these drugs on cellular signal transduction. In this study
      it was investigated whether HMG-CoA reductase inhibition could affect induction
      of the transcription factors c-Jun and c-Fos in smooth muscle cells, which play
      an important role in atherogenesis. SMC were preincubated for 12 h with or
      without lovastatin (5 microM) and subsequently stimulated with platelet derived
      growth factor (PDGF, 10 ng/ml) or angiotensin II (0.1 microM) for 1, 2, 4 and 12
      h or with phorbol myristate acetate (100 pM) for 2 h. Stimulation in the absence
      of the HMG-CoA reductase inhibitor led to a significant induction of c-Jun and c
      Fos. Lovastatin inhibited, PDGF-, angiotensin II- and PMA-mediated induction.
      Concomitant addition of mevalonate, farnesylpyrophosphate and
      geranylgeranylpyrophosphate prevented the effects of HMG-CoA reductase inhibition
      resulting in rescued expression of c-Jun and c-Fos. The suppression of these
      transcription factors was associated with a complete growth arrest. Viability was
      not affected by pretreatment with the HMG-CoA reductase inhibitor. The data
      demonstrate that lovastatin can suppress PDGF- and angiotensin II-mediated
      induction of c-Jun and c-Fos protein in human SMC. This inhibitory effect may
      prevent activation of numerous growth factor- and cell cycle- genes. Whether
      these findings contribute to the effects of statins in atherosclerosis remains to
      be further investigated.

PMID- 10205290
TI  - Influence of resin-based restoration materials on cytotoxicity in gingival
      fibroblasts.
AB  - Tooth-colored resin-based restoration materials have gained enormous significance
      in recent decades. Since the composites presently available still evidence
      various weaknesses, intensive research continues concerning them. In this study
      we tested the biocompatibility of six resin-based materials (Charisma, Solitaire,
      Definite, Tetric ceram, Ariston pHc and Compoglass) by means of cultured human
      gingival fibroblasts. Over a period of 9 days the cured resin-based materials
      were incubated with the fibroblasts. Cell growth, cell viability, and protein
      content was measured. The release of prostaglandin (PGE subset2) was also
      determined. There was a reduction of cell functions, related to the different
      resin-based materials. Protein content of the fibroblasts was significantly
      reduced (Kruskal Wallis test; p = 0.0001), depending on the material tested.
      Definite induced only minimal irritation, and there was correspondingly little
      contrast to the protein content of the controls. Solitaire induced the highest
      levels of irritation and the greatest reduction in protein content. Lactate
      production of fibroblasts also showed some significant reduction in contact with
      particular materials (p = 0.005). There were only small differences among the
      tested materials as concerns measured PGE subset2 release of the fibroblasts. The
      data suggest that the methods here employed may be quite useful in testing the
      cytotoxic potential of newly developed resin-based materials

PMID- 10205291
TI  - Levels of serum neopterin are increased in pancreatic cancer patients and
      correlate with the prognosis.
AB  - Neopterin has been recognized as a valid marker for cellular immune activation.
      Raised neopterin levels indicate the stimulation of macrophages and indirectly T
      cell activation. So far no data is available on serum neopterin in pancreatic
      cancer patients. PATIENTS: In this prospective clinical study serum neopterin
      values were evaluated in 83 patients with adenocarcinoma of the pancreas (PC), 47
      patients with chronic pancreatitis (CP), 8 patients with cystadenocarcinoma (CA)
      of the pancreas and 24 healthy controls (HC). RESULTS: Serum neopterin was
      significantly elevated in PC (p < 0. 05) and CA (p < 0.04) as compared to HC.
      There was no difference found between CP and HC. Pancreatic cancer patients with
      neopterin levels above 2 pmol/ml had a significantly better survival (p < 0. 05)
      regardless of stage. In stage III and IV (UICC) this difference was highly
      significant (p < 0.001). Serum levels of neopterin in resectable patients were
      also significantly correlated with increased survival and in multivariate
      analysis proved to be an independent prognostic factor. Neopterin in PC was
      neither correlated with sex, resectability nor with CA 19/9 and CEA. CONCLUSIONS:
      Patients suffering from PC who did show activated cellular immune response
      reflected in elevated neopterin levels above 2 pmol/ml had a significantly better
      prognosis regardless of tumor stage. In advanced stages elevated neopterin
      concentrations were significantly associated with increased survival. Cellular
      immune response seems to influence survival in these advanced stages to a higher
      degree as expected. These findings underline the possibility for supportive
      immunotherapy in this patient group.

PMID- 10205292
TI  - Familial Mediterranean fever. No role of Mycobacterium tuberculosis in ten
      patients.
AB  - BACKGROUND: Tuberculosis (TB) and Familial mediterranean fever (FMF) are two
      common diseases in our region, Turkey. Both share some properties in common: Both
      cause AA type amyloidosis and have association with some immunological
      abnormalities. Upon incidentally observing Mycobacterium tuberculosis in bone
      marrow biopsies of three patients with FMF in a previous study, we intended to
      elucidate this association prospectively. MATERIAL AND METHODS: In this study, we
      examined prospectively 10 FMF patients, 5 male and 5 female, with a median
      duration of 31 years disease activity. All were under colchicine therapy. They
      had no sign of renal involvement. The bone marrow biopsies of these patients were
      examined for the presence of M. tuberculosis by Polymerase chain reaction (PCR),
      BACTEC culture and pathological stains. Pathological examination was performed
      for the existence of granuloma and amyloid deposition by hematoxylin-eosin,
      Crystal Violet and Congo red stains. RESULTS: The examination of all bone marrow
      specimens by the mentioned methods suggest that Mycobacterium tuberculosis has no
      role in the ethiopathogenesis of FMF. Although the patients had a positive family
      history of 60% for tuberculosis and in 80% of them with positive tuberculin skin
      test. CONCLUSIONS: We concluded that although there seemed to be a kind of
      association between both diseases, this relationship is not via the direct
      existence of bacteria itself. Considering high family history and skin test
      positivity, one should look for the presence of autoimmune mechanisms under this
      suspicious relationship between tuberculosis and FMF. Also, this is the first
      study examined the state of amyloidosis in the bone marrow at an earlier stage of
      FMF without overt renal findings.

PMID- 10205293
TI  - Expression of a bile acid transporter in biliary epithelial cells from normal and
      cholestatic rat livers.
AB  - A sodium dependent bile acid carrier has recently been cloned and characterized
      in rat ileum. The present study demonstrates the presence of a mRNA species
      specific for the rat ileal bile acid carrier (r-IBAT) in rat biliary epithelial
      cells. Moreover, immunohistochemistry with a peptide specific antibody
      demonstrates protein expression in biliary epithelial cells from normal and bile
      duct ligated rat livers. Besides a cytoplasmic staining a predominant staining of
      the apical membrane could be observed. These observations indicate that biliary
      epithelial cells are involved in bile acid transport across the biliary tree. In
      addition the carrier could also play a role in the signal transduction of bile
      acid induced ductular secretion.

PMID- 10205295
TI  - A multiparametric approach to studies of self-organization of globular proteins 
AB  - This review analyzes the problem of using a multiparametric approach to studies
      of the process of globular protein folding. The principles of the most widespread
      contemporary physicochemical methods for studying the structural properties of
      globular protein molecules are considered. The specific information that can be
      obtained by using these structural methods is discussed.

PMID- 10205296
TI  - Fluorescence study of conformational transitions in the structure of myoglobin 
AB  - Fluorescence studies of myoglobin and Mb-like structures, apomyoglobin and the
      complex of apo-Mb with protoporphyrin IX, reveal both the similarity between
      them, which is due to a common type of polypeptide chain folding, and the
      distinctions imposed by the influence of the prosthetic group. Close resemblance
      of structures of holomyoglobin and its metal-free analog, PPIX--apo-Mb, points to
      a key role of specific interactions between the protein and the protoporphyrin
      macrocycle rather than the Fe-protein bond in the formation of Mb-like
      structures. In PPIX--apo-Mb, both the hydrophobic core and the important ionic
      bonds between different structural elements (<<salt bridges>>) stabilizing the Mb
      structure are almost completely retained. The bond between Fe and proximal His-F8
      allows additional integration of the structures of the heme cavity and the
      myoglobin molecule as a whole, providing its functional activity and highly
      cooperative conformational transitions. In all the myoglobin-like structures
      studied, a certain relationship is found between conformational states of the
      <<active center>>, the heme cavity, and the N-terminal part of the molecule. This
      is probably due to variations in the mutual orientation of the ABCDE and FGH
      helical domains, depending on the interactions between the protein, the
      prosthetic group, and the ligand in the heme crevice. The correlation between
      conformations of the N-terminal and heme regions found at a level of the globin
      tertiary structure is very important for understanding the mechanisms of homo-
      and heterotropic regulation in tetrameric hemoglobins.

PMID- 10205294
TI  - Possibilities of the method of step-by-step complication of ligand structure in
      studies of protein--nucleic acid interactions: mechanisms of functioning of some
      replication, repair, topoisomerization, and restriction enzymes.
AB  - X-Ray structure analysis is one of the most informative methods for investigation
      of enzymes. However, it does not provide quantitative estimation of the relative
      efficiency of formation of contacts revealed by this method, and when
      interpreting the data this does not allow taking into account the relative
      contribution of some specific and nonspecific interactions to the total affinity
      of nucleic acids (NA) to enzymes. This often results in unjustified
      overestimation of the role of specific enzyme--NA contacts in affinity and
      specificity of enzyme action. In recent years we have developed new approaches to
      analysis of the mechanisms of protein--nucleic acid interactions allowing
      quantitative estimation of the relative contribution of virtually every
      nucleotide unit (including individual structural elements) to the total affinity
      of enzymes to long DNA and RNA molecules. It is shown that the interaction
      between enzymes and NA on the molecular level can be successfully analyzed by the
      methods of synthesis and analysis, that is, step-by-step simplification or
      complication of the structure of a long NA-ligand. This approach allows the
      demonstration that complex formation including formation of contacts between
      enzymes and specific NA units can provide neither high affinity of the enzymes to
      NA nor the specificity of their action. Using a number of sequence-independent
      replication and repair enzymes specifically recognizing a modified unit in DNA
      and also some sequence-dependent topoisomerization and restriction enzymes as
      examples, it was shown that virtually all nucleotide units within the DNA binding
      cleft interact with the enzyme, and high affinity mainly (up to 5-7 of 7-10
      orders of magnitude) is provided by many weak additive interactions between these
      enzymes and various structural elements of the individual NA nucleotide units. At
      the same time, the relative contribution of specific interactions to the total
      affinity of NA is rather small and does not exceed 1-2 orders of magnitude.
      Specificity of enzyme action is provided by the stages of the enzyme-dependent NA
      adaptation to the optimal conformation and directly of catalysis: kcat increases
      by 3-7 orders of magnitude when changing from nonspecific to specific NA. In the
      present work we summarized our experience in studies of enzymes by the method of
      step-by-step complication of the ligand structure and performed a detailed
      analysis of the features of this approach and its possibilities for the study of
      protein--nucleic acid interactions on the molecular level.

PMID- 10205297
TI  - Plant subtilisins.
AB  - This review presents a systematization of available data on subtilisin-like
      serine proteinases of plants. Enzymatic and physicochemical properties of the
      enzymes, their structure and processing, as well as their biological functions
      and origin are considered. Subtilisin-like proteinases of plants have a number of
      substantial differences from such typical subtilisins as subtilisin BPN or
      subtilisin Carlsberg. The plant subtilisins are characterized by much greater
      molecular mass, long inserts and C-terminal regions, and several cysteine
      residues, while typical subtilisins have no cysteine residues, and thiol
      dependent bacterial subtilisins contain only one cysteine residue required for
      enzymatic activity.

PMID- 10205298
TI  - Determination of disulfide bonds in gamma-46 gliadin.
AB  - The disulfide bonds in gamma-46 gliadin were identified: Cys173--Cys192, Cys212-
      Cys291, Cys165--Cys199 (or Cys200), Cys283--Cys200 (or Cys199). The disulfide
      containing peptides were obtained by limited hydrolysis of the intact protein
      with chymotrypsin at an enzyme/substrate ratio of 1:1000 at 20 degrees C for 22 h
      with subsequent digestion of disulfide-containing fragments with trypsin and
      chymotrypsin. The locations of disulfide bonds were determined by sequencing
      disulfide-containing fractions and constituent peptides and comparison of the
      obtained sequences with the partial amino acid sequence of gamma-46 gliadin
      determined earlier.

PMID- 10205299
TI  - Dimer formation by tRNAs.
AB  - Available data on formation of dimers and other oligomers by "mature" tRNAs and
      the transcripts of their genes show that the dimers may be formed in vitro during
      the purification of individual tRNAs as well as on heating and subsequent cooling
      of tRNA preparations. The functional activity of dimers varies for different
      tRNAs. Structural analysis of tRNAs that are able or unable to form dimers
      suggests the importance of the hairpin melting temperature for dimer formation.
      Pathways of dimer formation and specific structural features of tRNA dimers are
      discussed.

PMID- 10205300
TI  - Unusual fast sedimenting mitochondria producing heavy DNA in the cells of aging
      coleoptiles of wheat seedlings 
AB  - A fraction of unusual fast sedimenting (10 min at 600-1700g) particles with
      properties of mitochondria has been detected in wheat seedlings. This fraction
      conventionally called "heavy" mitochondria amounts (by protein) to about 40% of
      the total subcellular particle fraction sedimented by 10 min centrifugation at
      17,000g. The specific feature of these "heavy" mitochondria in aging tissues is
      an ability to synthesize and even superproduce heavy (rho = 1.718 g/cm3)
      mitochondrial DNA (H-mtDNA). The share of "heavy" mitochondria sedimented in the
      interval between 1000 and 1700g and possessing the maximal H-mtDNA synthesis in
      aging coleoptiles is about 1.5-fold higher than that in young coleoptiles.
      Although "heavy" mitochondria are present in young plant organs, they seem to be
      unable to synthesize H-mtDNA; heavy mtDNA forms only in mitochondria of aging or
      old cells. Thus, aging in plants is accompanied by a change in population of
      mitochondria and appearance of the ability for selective H-mtDNA superproduction
      in a certain mitochondrial fraction. Mitochondria isolated from wheat coleoptiles
      are practically not stimulated by uncouplers. "Heavy" (600-1700g) and usual
      (4,300-17,400g) mitochondria are similar in respiration rates, cytochrome
      compositions, cytochrome c amount (per mg protein) and sensitivities to
      respiration inhibitors. However, "heavy" mitochondria contain (per mg protein)
      cytochromes b and aa3 by 10-20% and Ca2+ by 2-3-fold more than normal
      mitochondria. Ultrastructural analysis showed that the isolated fraction of fast
      sedimenting mitochondria consists of a suspension of closed membrane vesicles
      filled with cytoplasm and containing one or a few mitochondria. We observed
      similar structures in situ in vacuoles of parenchyma cells in the apical part of
      intact coleoptiles. The process of formation of such structures was detected by
      serial ultra-thin section analysis. It was shown that tonoplast protrudes into
      vacuoles, the separate mitochondria translocate into these protrusions, and then
      these structures separate. As a result, the suspended cytoplasmic bodies
      containing mitochondria appear in vacuoles. Appearance of these bodies containing
      mitochondria and, in particular, the superproduction of H-mtDNA in them correlate
      with processes of aging and cell transition to apoptosis.

PMID- 10205301
TI  - Regulation of pyruvate dehydrogenase complex activity in Ehrlich ascites
      carcinoma cells by Ca2+ and pyruvate.
AB  - The dependence of pyruvate dehydrogenase complex (PDC) activity on [Ca2+] was
      determined in Ehrlich ascites carcinoma cells at different pyruvate
      concentrations. The resulting family of curves had the following characteristics:
      a) bell-shaped appearance of all curves with maximum activity at 600 nM Ca2+; b)
      unchanged position of maxima with changes in pyruvate concentration; c)
      nonmonotonous changes in PDC activity with increasing pyruvate concentration at
      fixed [Ca2+]. Feasible mechanisms involving Ca2+-dependent phosphatase and kinase
      which are consistent with the experimental findings are discussed. To determine
      the steps in the chain of PDC reactions which determine the observed phenomena, a
      mathematical model is suggested which is based on the known data on the
      structural--functional relationships between the complex components--pyruvate
      dehydrogenase (E1), dihydrolipoyl acetyl transferase (E2), dihydrolipoyl
      dehydrogenase (E3), protein X, kinase, and phosphatase. To adequately describe
      the non-trivial dependence of PDC activity on [Ca2+] at different pyruvate
      concentrations, it was also necessary to consider the interdependence of some
      steps in the general chain of PDC reactions. Phenomenon (a) is shown to be due
      only to the involvement of protein X in the PDC reactions, phenomenon (b) to be
      due to changes in the activity of kinase, and phenomenon (c) to be due to
      dependence of acetylation and transacetylation rates on pyruvate concentration.

PMID- 10205302
TI  - A model for the spatial location of pyruvate dehydrogenase phosphatase in
      mammalian pyruvate dehydrogenase complex.
AB  - Recent experimental findings on the structural--functional features of pyruvate
      dehydrogenase phosphatase (PDP) isolated from various sources are compared. Two
      alternative mechanisms (a and b) of dephosphorylation of the E1 component in the
      pyruvate dehydrogenase complex (PDC) are discussed: a) the reaction occurs as a
      result of stochastic collisions of PDP and PDC, and the generation of an enzyme-
      substrate complex (PDP--E1--PDC) and dephosphorylation of the E1 component occur
      independently at different PDP binding sites on the PDC core; b) the
      dephosphorylation is performed simultaneously by a certain number of PDP
      molecules symmetrically bound on the PDC core. The second mechanism is suggested
      by the self-assembly theory of multicomponent enzyme systems and can be proved by
      kinetic experiments. Based on self-assembly principles and data on feasible
      binding sites of peripheral components of the PDC, the stoichiometry and mutual
      location of PDP, pyruvate dehydrogenase kinase, and the E1 component on the core
      of mammalian PDC are postulated to provide optimal functioning of the PDC.
      Structural mechanisms of stimulation of PDP activity by Ca2+ and polyamines are
      also discussed.

PMID- 10205304
TI  - Effects of growth temperature and pVM82 plasmid on fatty acids of lipid A from
      Yersinia pseudotuberculosis.
AB  - Effects of cultivation temperature (8 or 37 degrees C) and plasmid profile on the
      lipid A fatty acids of three isogenic Yersinia pseudotuberculosis strains
      (plasmidless (82-) and strains containing pVM82 (82+) or p57 (57+) plasmids)
      obtained by alkaline hydrolysis of the whole bacterial cells and differentiated
      from fatty acids of other membrane lipids were investigated. On the basis of the
      analysis, it is concluded that lipids A of all studied samples contain 3
      hydroxytetradecanoic and dodecanoic acids, a part of which exists as the 3
      dodecanoyloxytetradecanoic derivative. The effect of temperature appears in the
      higher contents of ester- and amide-linked 3-acyloxyalkanoic residues in lipid A
      from the "cold" variants of the bacteria and is determined by chromosomal genes.
      The plasmid effect is seen as various responses of the isogenic derivatives to
      change of growth temperature: in cells of strains 82+ and 82- grown in the cold,
      the share of lipid A fatty acids in the total population of cellular fatty acids
      is reduced, while in strains with plasmid p57 it is increased. The temperature
      variants of the 57+ strain differ by the low contents of amide-linked 3
      acyloxyalkanoic acids. Finally, lack of plasmid pVM82 in the "warm" variants of
      the bacteria results in accumulation of glycolipid molecules deprived of
      dodecanoic acid. Correlation between growth temperature and plasmid profiles, on
      one hand, and lipid A fatty acid composition and potential pathogenic properties
      of the Y. pseudotuberculosis, on the other hand, and also possible mechanisms of
      thermal adaptation of this organism are discussed.

PMID- 10205303
TI  - Calcium ions modulate regulation of smooth muscle contraction mediated by
      phosphorylation of myosin regulatory light chains.
AB  - The effect of calcium ions on conformational changes of F-actin initiated by
      decoration of thin filaments with phosphorylated and dephosphorylated heavy
      meromyosin from smooth muscles was studied by fluorescence polarization
      spectroscopy. It is shown that heavy meromyosin with phosphorylated regulatory
      light chains (pHMM) promotes structural changes of F-actin which are typical for
      the "strong" binding of actin to the myosin heads. Heavy meromyosin with
      dephosphorylated regulatory light chains (dpHMM) causes conformational changes of
      F-actin which are typical for the "weak" binding of actin to the myosin heads.
      The presence of calcium enhances the pHMM effect and attenuates the dpHMM effect.
      We propose that a Ca2+-dependent mechanism exists in smooth muscles which
      modulates the regulation of actin--myosin interaction occurring via
      phosphorylation of myosin regulatory light chains.

PMID- 10205306
TI  - L-arginine-nitric oxide metabolism. Glutamine: A new player in this metabolic
      game? 

PMID- 10205305
TI  - Apoptosis of unstimulated human lymphocytes and DNA strand breaks induced by the
      topoisomerase II inhibitor etoposide (VP-16).
AB  - Etoposide (VP-16)-induced DNA strand breaks and repair and apoptosis of
      unstimulated human lymphocytes have been studied using DNA comet assay,
      electrophoresis of low-molecular-weight DNA extracts, and fluorescence
      microscopy. Incubation of unstimulated human lymphocytes with VP-16 (50-200
      microg/ml) for 3 or 24 h induced apoptosis. This conclusion is supported by
      results of morphological studies, evaluation of the proportion of hypodiploidy
      and internucleosomal degradation of DNA in lymphocytes. Etoposide-induced
      formation of DNA strand breaks preceded the appearance of these conventional
      apoptotic manifestations. The number of single-strand breaks depended on VP-16
      concentration, and 2-3 h after its removal from the incubation medium they were
      repaired. The hydroxyl group at the C-4; position of the etoposide
      dimethoxyphenol ring may be responsible for the formation of single-strand
      breaks. Double-strand breaks were unrepaired 20 h after the change of the
      incubation medium. The number of double-strand breaks and a proportion of
      apoptotic cells did not exhibit any dependence on VP-16 concentration and/or
      duration of cell exposure to this agent. We suggest that the cytotoxic effect of
      VP-16 on unstimulated lymphocytes is mediated by a topoisomerase II isoform,
      topoisomerase II-beta, which is localized in the nucleolus and is not related to
      the cell cycle.

PMID- 10205307
TI  - Glutamine-containing TPN: a question of life and death for intensive care unit
      patients?

PMID- 10205308
TI  - Nutrition and lung function in the critically ill patient.

PMID- 10205309
TI  - Dietary glutamine supplementation reduces plasma nitrate levels in rats.
AB  - It was recently shown that L-glutamine inhibits vascular nitric oxide (NO)
      production in vitro. The present study investigated the effect of glutamine
      enriched enteral diets on in vivo NO production in the rat. Nitrate, the stable
      end-product of NO production, was measured in plasma and 24 h urine collections
      in glutamine supplemented rats (6.25%, 12.5% and 25% w/w) and compared to the
      effect of isocaloric, nitrogenous control diets. Glutamine supplementation
      increased plasma levels of glutamine (up to 91%), arginine (up to 17%) and
      citrulline (up to 54%). After 1 week of glutamine supplementation plasma nitrate
      levels were significantly reduced by 50% compared to control (P < 0. 0001);
      irrespective of the amount of supplementation. No further decrease was observed
      after 2 weeks of feeding. No differences in daily urinary losses were found
      between the groups. These results point to an in vivo inhibitory effect of
      glutamine supplemented enteral feeding on NO production.

PMID- 10205310
TI  - Body-water compartments measured by bio-electrical impedance spectroscopy in
      patients with chronic obstructive pulmonary disease.
AB  - It was previously demonstrated that single frequency bio-electrical impedance
      (BIA) measurement at 50 kHz is a useful method to assess total body water (TBW)
      in patients with chronic obstructive pulmonary disease (COPD). In the present
      study it was examined whether bio-electrical impedance spectroscopy (BIS) could
      predict extracellular water (ECW) and improve the prediction of TBW in these
      patients. TBW and ECW (corrected bromide space) were measured by deuterium and
      bromide dilution. In 37 COPD patients prediction equations were obtained using
      BIS (5-500 kHz) measurements, and these were cross validated in a second group of
      40 COPD patients. All patients were in a clinically stable condition. TBW
      predicted by BIS was not significantly different from actual TBW and demonstrated
      a comparable standard error of estimate (SEE) as found previously in healthy
      subjects (male symbol correlation coefficient: r = 0.88, SEE: 2.3 L, female
      symbol r = 0.85, SEE: 2.9 L). Predicted ECW using BIS-measurements was not
      significantly different from measured ECW (male symbol r = 0.75, SEE: 1.4 L,
      female symbol r = 0.73, SEE: 1.2 L), but the error in the prediction was
      relatively large and the correlation between predicted and actual ECW relatively
      low compared to most studies in healthy subjects. Predicted TBW using BIS was
      comparable to actual TBW, but presented no improvement of the prediction of TBW
      using BIA at 50 kHz and a patient specific regression equation. The error of the
      prediction of ECW by BIS limits the ability to predict fluid shifts in individual
      patients with clinically stable COPD.

PMID- 10205311
TI  - Use of a mixture of medium-chain triglycerides and longchain triglycerides versus
      long-chain triglycerides in critically ill surgical patients: a randomized
      prospective double-blind study.
AB  - Twenty critically-ill surgical patients who needed total parenteral nutrition
      were randomly enrolled in a double-blind study comparing two intravenous fat
      emulsions: one containing a mixture of 50% medium-chain triglycerides and 50%
      long-chain triglycerides and another containing 100% longchain triglycerides. The
      purpose of this study was to investigate metabolic and biochemical differences
      between both emulsions with special reference to liver enzymes. After a baseline
      period of 24 h with only glucose and NaCl infusion, the lipid emulsion was added
      continuously during 24 h over 5 days. The parenteral nutrition was administered
      in mixture bags containing amino-acids, glucose and lipids together. Two-thirds
      of the non-protein calories were administered as glucose 40% and one third as
      either long-chain triglycerides or a mixture of medium-chain triglycerides and
      long-chain triglycerides. The total amount of non-protein calories received was
      the measured energy expenditure during the baseline period plus 10% and was fixed
      during the study. Plasma substrate concentrations, energy expenditure, and
      nitrogen balance were determined and arterial blood samples were taken. No toxic
      effects or complications attributable to one of the two emulsions were observed.
      There was no significant difference in energy expenditure, nitrogen balance,
      liver function tests, carnitine, transferrin, pre-albumin, albumin, cholesterol,
      triglycerides and free fatty acids. The only parameter that showed a different
      pattern of reaction between the two emulsions was serum bilirubin concentration.
      In this study no evidence of any advantageous effect of a mixture of medium-chain
      triglycerides and long-chain triglycerides was seen.

PMID- 10205314
TI  - Reply to Dr moreno 

PMID- 10205312
TI  - Comparison between two fat emulsions: Intralipid 30 cent vs intralipid 10 cent in
      critically ill patients.
AB  - Fat emulsions, Intralipid 30% and Intralipid 10% were compared in terms of the
      resulting plasma levels of different lipid components and clinical tolerance in
      critically-ill patients with multi-injuries. Sixteen critically-ill patients with
      severe systemic inflammatory response were randomly assigned to two groups, each
      one comprised of eight patients. Each group was administered the same quantity of
      fat/Kg/day either Intralipid 30% or Intralipid 10%. The infusion lasted 12|h
      daily for 6 days. During the infusion of the fat emulsion, a lower median plasma
      concentration of triglycerides, phospolipids and free cholesterol was observed in
      patients who received Intralipid 30% compared with those who received Intralipid
      10%. The above observations were sustained 4 h after the termination of the
      infusion. Free fatty acids had a higher mean plasma concentration in the group of
      patients who received Intralipid 30%. There were no differences between the two
      groups as far as the median plasma concentration of cholesterol and lipoproteins
      (LDL, HDL, VLDL) are concerned. On the contrary, there was an increase in LpX in
      the Intralipid 10% group. From the above findings, we draw the conclusion that
      Intralipid 30% revealed better profiles of different lipid components than
      Intralipid 10% in critically-ill patients. The new emulsion of higher
      concentration in triglyceride was proved clinically safe and its use is suggested
      for critically-ill patients who require total parenteral nutrition.

PMID- 10205313
TI  - Central venous catheter occlusion in home parenteral nutrition patients.

PMID- 10205315
TI  - Folate and colon cancer: a fascinating puzzle we have yet to complete.

PMID- 10205316
TI  - Effect of folate supplementation on DNA methylation of rectal mucosa in patients
      with colonic adenomas: correlation with nutrient intake.
AB  - We have evaluated the effect of folate supplementation (5 mg/day) on global
      deoxyribonucleic acid (DNA) methylation status of the rectal mucosa of 20
      patients with resected colonic adenomas in a prospective, controlled, cross-over
      study. Baseline values of DNA methylation were inversely correlated with caloric
      (P = 0.03) and fat intake (P = 0.05) and patients harbouring multiple polyps
      consumed significantly more calories (P = 0.0006), fat (P = 0.009) and
      carbohydrates (P = 0.009) as compared to patients having one single lesion.
      Folate supplementation resulted in a significant decrease of DNA hypomethylation
      in 7/20 patients (P = 0.05) which returned to previous values after placebo
      treatment. This effect was significantly correlated with number of polyps, with
      all the responders presenting one single lesion, whereas 8/13 of the non
      responders had multiple ones (chi2 = 7.17, P = 0.007). In conclusion, folate
      supplementation may decrease degree of DNA hypomethylation, but only in patients
      with one single polyp. In those with multiple lesions, other nutritional factors
      such as caloric and fat intake, may be more determinant.

PMID- 10205317
TI  - Accelerated splanchnic amino acid uptake after cardiac surgery.
AB  - Energy expenditure increases after cardiac surgery, but changes in peripheral
      tissue metabolism do not explain this increase. We hypothesized that the
      splanchnic region is a major contributor to the postoperative hypermetabolism,
      and this should be reflected in the exchange of amino acids across the splanchnic
      bed. We measured systemic and regional (splanchnic and leg) amino acid exchange,
      oxygen uptake and hemodynamics in 22 elective coronary bypass grafting patients
      postoperatively after arrival to the intensive care unit, 2 h later, and after
      stabilization of hemodynamics. Splanchnic uptake of glutamine (50 +/- 37
      micromol/min/m2 to 78 +/- 37 micromol/min/m2, P < 0.05) and three of the
      gluconeogenetic amino acids, alanine (115 +/- 52 micromol/min/m2 to 183 +/- 70
      micromol/min/m2, P < 0.05), serine (18 +/- 10 micromol/min/m2 to 26 +/- 13
      micromol/min/m2) and threonine (20 +/- 8 micromol/min/m2 to 28 +/- 8
      micromol/min/m2) increased during the observation period. Similarly, the oxygen
      consumption by the splanchnic region increased while splanchnic blood flow
      remained stable. A correlation between oxygen and amino acid uptake by the
      splanchnic bed was observed during the study period. Femoral exchange of
      glutamine and alanine did not change, although femoral blood flow and oxygen
      consumption increased during rewarming. High metabolic activity was observed in
      the splanchnic region during the early postoperative phase after hypothermic
      cardiac surgery. The increased plasma amino acid concentration indicates a
      release of amino acids from other sources than the peripheral muscle.

PMID- 10205318
TI  - Nutritional support in children undergoing bone marrow transplantation.
AB  - Nutritional status and 'well-being' were compared prospectively in 39 children
      (mean age 8.1 years) who received nutritional support following bone marrow
      transplantion (BMT): 20 received enteral tube feeding (ETF; six received
      parenteral nutrition [PN] subsequently) and 19 with oral mucositis received PN
      (one received ETF subsequently). Poor nutritional status (height for age and/or
      weight for height and/or mid-arm circumference z-scores <-1) was present in 18
      patients and was associated with a longer hospital stay (P = 0. 01). Both ETF and
      PN groups were comparable with respect to age, pretransplant nutritional status
      and conditioning regimens. No significant deterioration in anthropometric indices
      in either group occurred following BMT. However, significant correlations were
      found between the duration of ETF (and not PN) and improvements in nutritional
      status. Furthermore, PN was associated with more frequent exocrine pancreatic
      insufficiency than ETF (P = 0.001). Oral mucositis was associated with poorer
      'well being' at the start of PN compared with ETF (P < 0.0001), but this was
      reversed by the end of PN. Bone marrow recovery, hospital stay and positive blood
      cultures were similar in the two groups. Hypomagnesaemia, hypophosphataemia and
      biochemical zinc deficiency were common in both groups but hypoalbuminaemia and
      biochemical selenium deficiency were worse in the PN group. In conclusion, both
      ETF and PN are effective in maintaining nutritional status post-BMT. When ETF is
      tolerated, it is associated with better nutritional response. With the existing
      ETF and PN regimens close monitoring of the trace element and mineral status is
      required.

PMID- 10205320
TI  - Glutamate metabolism of the heart during coronary artery bypass grafting.
AB  - Glutamate infusion has been shown to exert beneficial hemodynamic effects in
      patients with heart failure after cardiac surgery. To elucidate the underlying
      mechanism we studied the possibility that glutamate is a Krebs-cycle precursor in
      the human heart. Therefore [1-13C]glutamate was infused in order to show
      production of 13CO2 by the heart. In five patients a primed constant infusion of
      [1-13C]glutamate was started 2|h before the start of sampling from coronary sinus
      and arterial blood. Plasma concentrations of glutamate and glutamine were
      determined by high pressure liquid chromatography. Blood concentration of CO2 and
      enrichment of [1-13C]glutamate, [1-13C]glutamine and [1-13C]glutmaine and 13CO2
      were measured by GC-IRMS. The results show that approximately 85% of [1
      13C]glutamate taken up by the heart is released released as 13CO2. These results
      show that synthesis of Krebs-cycle intermediates is a major fate of the glutamate
      extracted by the human heart.

PMID- 10205319
TI  - Preoperative oral carbohydrate administration reduces postoperative insulin
      resistance.
AB  - Infusions of carbohydrates before surgery reduce postoperative insulin
      resistance. We in-vestigated the effects of a carbohydrate drink, given shortly
      before surgery, on postoperative metabolism. METHOD: Insulin sensitivity, glucose
      turnover ([6,6, 2H2]-D-glucose) and substrate utilization were measured using
      hyperinsulinemic normoglycemic clamps and indirect calorimetry in two matched
      groups of patients before and after elective colorectal surgery. The drink group
      (n = 7) received 800 ml of an isoosmolar carbohydrate rich beverage the evening
      before the operation (100 g carbohydrates), as well as another 400 ml (50 g
      carbohydrates) 2 h before the initiation of anesthesia. The fasted group (n = 7)
      was operated after an overnight fast. RESULTS: After surgery, energy expenditure
      increased in both groups. Endogenous glucose production was higher after surgery
      and the difference was significant during low insulin infusion rates in both
      groups (P < 0.05). The supressibility of endogenous glucose production by the two
      step insulin infusion was similar pre-and postoperatively in both groups. At the
      high insulin infusion rate postoperatively, whole body glucose disposal was more
      reduced in the fasted group (-49 +/- 6% vs -26 +/- 8%, P < 0.05 vs drink).
      Furthermore, during high insulin infusion rates, glucose oxidation decreased
      postoperatively only in the fasted group (P < 0. 05) and postoperative levels of
      fat oxidation were greater in the fasted group (P < 0.05 vs drink). Only minor
      postoperative changes in cortisol and glucagon were found and no differences were
      found between the treatment groups. CONCLUSIONS: Patients given a carbohydrate
      drink shortly before elective colorectal surgery displayed less reduced insulin
      sensitivity after surgery as compared to patients who were operated after an
      overnight fast.

PMID- 10205321
TI  - Amino acids may be intrinsic regulators of protein synthesis in response to
      feeding.

PMID- 10205322
TI  - Effect of nitric oxide synthase inhibition on the hypercatabolic response to
      injury in endotoxemic malnourished rats.

PMID- 10205324
TI  - Intravascular disruption of central venous ports.
AB  - Intravasal catheter disruption is a rare complication of central venous ports.
      Main causes are chronic trauma due to compression of the catheter between
      clavicle and first rib, or primary damage by sharp instruments during insertion.
      Utilizing the subclavian route, a more lateral insertion can minimize the risk of
      catheter compression. Regular postoperative X-ray controls can help to recognize
      progressive catheter compression. In the case of significant compression, early
      replacement is advisable to avoid disruption. Percutaneous transvenous snare
      technique is the therapy of choice to retrieve dislocated fragments.

PMID- 10205323
TI  - Effect of alpha-tocopherol pretreatment on high energy metabolites in rabbit
      skeletal muscle after ischemia-reperfusion.
AB  - The ability of skeletal muscle to recover high energy phosphate compounds in
      response to pretreatment with vitamin E was investigated in a rabbit hindlimb
      ischemia/reperfusion model (2. 5 h/2 h). High energy metabolites were measured in
      the adductor magnus muscle of untreated animals and compared to the treatment
      group (all rac-alpha-tocopheryl acetate, 3 mg/kg body weight, supplemented i.v.
      before the onset of ischemia). Phosphocreatine (PCr) levels decreased after
      ischemia more than 65% in untreated and treatment groups, but tended to recover
      in treatment group after reperfusion. Adenosine triphosphate (ATP) values
      decreased by 50% of basal level after reperfusion in the untreated group, whereas
      alpha-tocopherol pretreatment prevented ATP depletion.

PMID- 10205325
TI  - Effect of critical illness and nutritional support on mucosal mass and function.

PMID- 10205326
TI  - Differences in immune status between well-nourished and malnourished head and
      neck cancer patients.
AB  - Malnutrition is reported to occur in approximately 30% of head and neck cancer
      patients. Also, impaired immunocompetence is described as a common phenomenon in
      this patient group. The purpose of this study was to assess the possible
      relationship between malnutrition and some prognostically important immune
      parameters in head and neck cancer patients. Thirty-two malnourished (recent
      weight loss >/= 10%) and 34 well-nourished patients undergoing curative treatment
      for advanced head and neck cancer were studied prospectively, and six parameters
      of their immune status (leucocytes, lymphocytes, lymphocyte phenotyping,
      monocytes, HLA-DR expression on monocytes and serum interleukin-10) were
      determined on the day of panendoscopy. Reference values for monocytes, HLA-DR
      expression and interleukin-10 were obtained from 43 healthy controls. Although
      the number of monocytes was elevated in both patient groups, the HLA-DR
      expression on these monocytes was significantly lower in the malnourished than in
      the well-nourished and control groups. Tumor stage, tumor localization,
      recurrence after initial radiotherapy, age and gender were not correlated to HLA
      DR expression. No relationships emerged between nutritional status and lymphocyte
      subsets. Malnourished head and neck cancer patients show a significantly lower
      HLA-DR expression on monocytes than well-nourished ones and healthy controls.
      According to the literature this would imply an increased risk for postoperative
      complications. Indeed, postoperative complications occur more frequently in
      malnourished than in well-nourished patients.

PMID- 10205327
TI  - Validation and comparison of two computerized methods of obtaining a diet
      history.
AB  - The aim of this study was to validate two computerized methods of obtaining a
      diet history (DH and EBIS). The food consumption of 12 men and eight women was
      calculated by weighing each food item over a period of 8 days. Thereafter the
      diet history was taken over this period by using both programs alternatively. The
      intake of energy, protein, fat and carbohydrates, and 10 further nutrients was
      evaluated and the percentage difference calculated. In general, the intake of
      nutrients calculated from the diet history tended to be underestimated by most of
      the people interviewed. The mean daily intake of the nutrients calculated from
      the DH program deviates from -34% to +20% (mean SD = 48.1) and -35% to +15% for
      EBIS (mean SD = 28.1). In conclusion, both computerized methods proved useful for
      epidemiological studies, but not for the determination of deficiencies in
      individuals.

PMID- 10205328
TI  - Effect of nutritional status on use of health care resources by patients with
      chronic disease living in the community.
AB  - The prevalence of malnutrition in patients with chronic disease living in the
      community in the UK is around 8%. Whether such patients experience greater
      morbidity and mortality or make increased use of health care resources is
      unknown. The aim of this study was to investigate how the use of health care
      resources by patients with chronic disorders of the respiratory, gastrointestinal
      and neurological systems varied by nutritional status. We used longitudinal data,
      collected since 1987, which formed part of the General Practice Research Database
      in the UK. Subjects were 11 357 men and women aged 18 years or over. Main
      outcomes were consultation rates in general practice, prescription rates,
      hospital referral rates, hospital admission rates and mortality. Consultation and
      prescription rates were lowest amongst patients whose body mass index (BMI) was
      between 20 and 25. Rates were higher in patients whose BMI was below 20, or 25
      and above. There was no statistically significant relation between rate of
      hospital outpatient referral and nutritional status, but both hospital admission
      rate and mortality were greatest in those people whose BMIs were below 20 and
      declined as BMIs increased. In patients with differential use of health care
      resources in both primary care and hospital practice, and with differences in
      mortality.

PMID- 10205329
TI  - Effects of a partially hydrolyzed guar gum on intestinal absorption of
      carbohydrate, protein and fat: a double-blind controlled study in volunteers.
AB  - Some dietary fibres have been shown to affect the rate of absorption of dietary
      carbohydrate, protein and fat as well as exocrine pancreatic function. The aim of
      the study was to examine the effect of partially hydrolysed guar gum (BENEFIBER),
      on normal absorption of glucose, amino acid (arginine) and fat. In addition
      hepatic, pancreatic, renal and haematological side effects were evaluated.
      METHODS: A double blind, randomized and cross-over design was used. Each subject
      served as its own control. Ten healthy male volunteers participated in the study.
      Each subject was randomly assigned to two different dietary regimes for a period
      of 7 days each. The study was repeated with the other diet for another 7-day
      period after an interval of at least 1 week. In one study period the subjects
      took liquid formula diet without fibre and during the other study period they
      took the same diet with fibre. RESULTS: The results of the study demonstrated
      that BENEFIBER did apparently not interfere with the normal absorption of
      glucose, amino acid and fat. In keeping with these observations, insulin release
      and exocrine pancreatic function were not affected. Haematological, renal and
      hepatic toxicity were not observed in association with BENEFIBER consumption.
      CONCLUSION: We conclude that BENEFIBER is a safe source of soluble fibre.

PMID- 10205330
TI  - A case of kwashiorkor in the UK.
AB  - A case of kwashiorkor in a British child of Caucasian origin is described. The 5
      year-old boy was referred to hospital for investigation of a persistent anaemia,
      but on examination was found to have classical features of kwashiorkor. He was
      stunted with both height and weight below the fifth centile and had mild pitting
      oedema in both legs. His hair was pale and easily pluckable and a soft liver edge
      was palpable. Plasma albumin concentration was 16 g/l and the plasma amino acid
      pattern, which revealed markedly reduced levels of essential but normal to high
      non-essential amino acids, was similar to that described in kwashiorkor in
      Uganda. A dietary history revealed that for about 2 years the child's diet had
      contained very little protein but adequate energy and had been supplemented with
      multivitamin pills. There was no evidence of other pathology, neglect or abuse
      and the child responded rapidly to refeeding with a balanced diet.

PMID- 10205332
TI  - Progress in perioperative enteral tube feeding.

PMID- 10205331
TI  - Enteral nutrition by percutaneous endoscopic gastrojejunostomy in severe
      hyperemesis gravidarum: a report of two cases.
AB  - We describe the first two cases in which percutaneous endoscopic
      gastrojejunostomy was used as a means to provide enteral nutrition in severe
      hypermesis gravidarum. The use of this method of enteral access provided an
      alternative to parenteral nutrition, was well tolerated, cost-effective and had
      no major complications. In both cases the nutritional goal for mothers as well as
      appropriate fetal growth and development were achieved.

PMID- 10205333
TI  - Perioperative artificial nutrition in elective surgery: an impact study of French
      guidelines.
AB  - OBJECTIVE: In France, the consensus conference, held on 16 December 1994,
      produced guidelines on perioperative artificial nutrition (AN) use in patients
      undergoing elective surgery. The aim of this study was to assess the impact of
      these guidelines on practice patterns. METHODS: The study was a practice pattern
      study with a 'before-after' design and a control group in England. A
      retrospective cross-sectional sample of adult patients undergoing elective
      resection of the digestive tract was collected in France and England before and
      after the consensus conference. RESULTS: Malnourished patients received
      postoperative AN in 94% of 'before' cases and 82% 'after' but inadequate
      preoperative AN (40% 'before' and 26% 'after'). Postoperative AN appeared to be
      over-prescribed in non-malnourished patients without prolonged postoperative
      fasting (70% 'before' and 65% 'after'). In the English sample there was no
      significant variation in AN use between 'before' and 'after' periods. CONCLUSION:
      This study shows that clinical guidelines disseminated by consensus conference
      had a low impact on practice patterns in France and thus confirms the need to
      enforce the dissemination of the guidelines.

PMID- 10205334
TI  - Antioxidant transport by the human placenta.
AB  - We investigated the transfer of three antioxidants - melatonin, S-adenosyl
      methionine (SAM) and various forms of vitamin E - across the term, normal human
      placenta. The transport technique involved the single, isolated placental
      cotyledon system in vitro. Melatonin crossed the placental rapidly, equally to
      the freely diffusible marker, antipyrine. There was no biotransformation of the
      agent. SAM was transferred slowly, similarly to passively transported L-glucose
      as a marker. There was a breakdown of SAM to at least one other derivative; the
      process appeared to be nonenzymatic. Vitamin E was transferred slowly, at a rate
      only 10% of L-glucose. The natural RRR (nonracemic) form of vitamin E was
      transported best. Free vitamin, rather than the acetate seems to be transferred
      best, a finding that will require further study.

PMID- 10205335
TI  - Effects of alimentary whole proteins versus their small peptide hydrolysates on
      liver and skeletal muscle during the acute inflammation phase in the rat.
AB  - Acute inflammation induces changes in liver proteins with an increase in
      synthesis of positive acute-phase proteins such as alpha1-acid glycoprotein
      (alpha1-AGP) and a decrease in synthesis of negative acute-phase proteins such as
      albumin. This is associated with muscle wasting, mediated by increased
      proteolysis and impaired protein synthesis. As protein metabolism can be altered
      in other situations (malnutrition, growth) by the form of the dietary nitrogen,
      we studied the effects of the molecular form of nitrogen on liver and skeletal
      muscle adaptation, looking at gene expression for two acute-phase proteins
      (albumin and alpha1-AGP) and a number of muscle proteins (alpha1-actin, ubiquitin
      and C9 proteasome subunit). Two groups of 24 Wistar rats (250 g) were injected
      S/C with 0.125 ml turpentine/rat and were fed one of two liquid diets. These
      diets had caloric, nitrogen, carbohydrate and lipid content but differed in the
      molecular form of the nitrogen source (whole protein [WP] versus peptide
      hydrolysate [PH]). Liver and muscle adaptation were studied at 18, 42 or 66 h
      after turpentine injection. Weight, deoxyribonucleic acid and protein content of
      the liver were significantly higher with the WP diet than with the PH diet at 42
      h and 66 h. There was more alpha1-AGP messenger ribonucleic acid (mRNA) at 18 h
      and less albumin mRNA at 42 h. Thus, the PH diet causes a more rapid increase in
      alpha1-AGP mRNA content and a smaller decrease in albumin mRNA content after
      turpentine injection than the WP diet. However, the changes in plasma acute-phase
      proteins (albumin and alpha1-AGP) were similar with the two diets. In skeletal
      muscle, there was no change in mRNA levels for the C9 proteasome subunit at any
      time point with both diets compared to the controls. However, there were greater
      ubiquitin mRNA levels at 18|h and less alpha-actin mRNA levels at 18 h, 42 h and
      66 h following turpentine injection in the two dietary groups than in the
      controls. These results suggest that the molecular form of nitrogen ingested
      regulates hepatic gene transcription or mRNA stability of acute-phase proteins,
      during the early period of inflammation, but did not affect the expression of
      muscle proteins, which was altered by turpentine injection. Post-transcriptional
      control of acute-phase protein genes may contribute to the maintenance of similar
      plasma levels.

PMID- 10205336
TI  - Plasma and red blood cell fatty acid composition in small for gestational age
      term infants fed human milk or formula.
AB  - The purpose of the present study was to evaluate the effects of feeding human
      milk or milk formula on the fatty acid composition of plasma and red blood cell
      (RBC) lipids in at term small for gestational age infants (SGA) for the first 3
      months of life. One group of infants received a formula with a linoleic:alpha
      linolenic acid ratio of 10:1 (MF group). Another group served as control and
      received their own mother's milk (HM group). Blood samples were taken at birth
      and at 1 week, 4 weeks, and 3 months of life. Plasma and RBC fatty acid
      composition were analyzed by gas liquid chromatography and results of total
      plasma lipids were expressed as concentrations by adding an internal standard.
      Concentrations of saturated and monounsaturated fatty acids increased in total
      plasma lipids with age in all infants. In contrast, those fatty acids decreased
      when results were expressed as percentages of total fatty acids. Long-chain
      polyunsaturated fatty acids (LCP) decreased regardless of how results were
      expressed, but the absolute concentrations of these fatty acids in plasma
      available for tissue accretion were greater than suggested by the percentage
      results. Plasma and RBC docosahexaenoic acid (22:6n-3) decreased in the MF group
      in comparison to the HM group. Arachidonic acid (20:4n-6) was lower in plasma of
      MF-fed infant but not in RBC phospholipids. We conclude that term SGA infants fed
      an adapted milk formula with a linoleic:alpha-linolenic acid ratio of 10:1 but
      devoid of LCP may lead to a low n-3 LCP status.

PMID- 10205337
TI  - Bulking fibre prevents translocation to mesenteric lymph nodes of an efficiently
      translocating Escherichia coli strain in rats.
AB  - BACKGROUND: starvation for 24 h prior to experimental haemorrhage increases
      bacterial translocation in rats. Forty-eight hours starvation alone causes
      pronounced microbiological changes in caecal contents and a marked increase in
      bacterial adherence to caecal epithelium. The aim of the present study was to
      examine whether bulking fibre prevents these microbiological changes induced by
      starvation, i.e. mucosal adherence and/or bacterial translocation with and
      without haemorrhage in rats. METHODS: 32 rats were inoculated with the
      translocating Escherichia coli strain Kl-C1. Groups of these rats were then
      starved for 48 h with or without access to bulking fibre. An additional group of
      rats was given bulking fibre and subjected to haemorrhage. A control group was
      untreated and given regular food. Samples were taken from caecal contents, caecal
      epithelium, mesenteric lymph nodes and blood. A biochemical fingerprinting method
      was used to characterize and compare E. coli strains in all samples. RESULTS:
      ingestion of bulking fibre alone for 48 h significantly reduced the frequency of
      Kl-C1 both in caecal contents and on caecal epithelium and completely prevented
      translocation of the strain, compared to starvation without bulking fibre for 48
      h. Enforced stress (haemorrhage) increased bacterial translocation to the same
      level as starvation for 48 h. E. coli phenotypes found in mesenteric lymph nodes
      were also found adhering to the caecal epithelium. CONCLUSIONS: The presence of
      bulking fibre in gut lumen, by unknown mechanisms, reduces the frequency of an
      inoculated translocating strain of E. coli in caecal contents and on caecal
      epithelium and prevents its translocation to mesenteric lymph nodes.

PMID- 10205338
TI  - At which body mass index and degree of weight loss should hospitalized elderly
      patients be considered at nutritional risk?
AB  - The Subjective Global Assessment, the Nutrition Risk Score and a Danish
      counterpart are simple screening methods to detect patients at risk of nutrition
      related complications. The cut-off points used in the screening are a body mass
      index (BMI) less than 20 kg/m2 (18. 5 kg/m2 in the Danish version) and weight
      loss more than 5% during the last 1-6 months - regardless of age. This review of
      the literature indicates that the optimal range of BMI for elderly people is
      increasing from 20 to 25 kg/m2 to 24-29 kg/m2. It also suggests that a clinically
      significant weight loss for the elderly is around 5% annually, less than in
      younger age groups. And finally, even though intervention studies have shown an
      overall positive effect of nutritional support of the elderly patients, there
      seems to be a high percentage of the old, especially those initially
      malnourished, who will not benefit from the support. The conclusion is that other
      cut-off points should be used for the elderly (65+ years) patients, i.e. BMI less
      than 24 kg/m2 or any degree of weight loss. This means that nutritional support
      will be initiated in time to reduce the nutrition related complications.

PMID- 10205339
TI  - Stability issues in home parenteral nutrition.
AB  - Home parenteral nutrition (HPN) is a method of providing nutrients, fluid and
      electrolytes intravenously to patients with a malfunctioning gastrointestinal
      tract, at home. Parenteral nutrition (PN) formulations are checked carefully for
      stability by the hospital pharmacist before the bags are made. However, there are
      many differences between supplying PN regimens to in-patients on the ward and to
      patients at home. Transportation between the hospital and home may be prolonged
      if the patient lives a long way from the hospital and may not be straight
      forward. A number of factors can adversely affect the stability of the PN, which
      in turn can cause complications such as line blockage; or even life-threatening
      events, such as pulmonary embolism. The hospital team caring for HPN patients
      needs to be aware of these stability issues if complications resulting from
      incompatibilities of the solutions in the bags or the infusion line are to be
      avoided.

PMID- 10205340
TI  - Effects on skeletal muscle amino acids and whole body nitrogen metabolism of
      total parenteral nutrition following laparoscopic cholecystectomy and given to
      healthy volunteers.
AB  - In this descriptive study total parenteral nutrition (TPN) without glutamine was
      administered over 2 days to patients undergoing laparoscopic cholecystectomy (n =
      8) and to volunteers (n = 8). Effects on muscle amino acids and nitrogen economy
      were studied. Muscle protein synthesis, determined by ribosome and polyribosome
      concentrations were measured in the patients. In both patients and volunteers the
      muscle amino acid patterns indicated muscle protein catabolism. Decreases in
      glutamine were seen in both groups (21.8 +/- 4.6% in patients and 17.5 +/- 5.4%
      in the volunteers). In both groups a negative nitrogen balance was seen (-4.1 +/-
      1.2 gram and -10.3 +/- 2.4 gram respectively). The patients also showed decreased
      ribosome (by 13.7 +/- 4.5%) and polyribosome concentration (by 17.4 +/- 4.6%),
      indicating a decrease in muscle protein synthesis. No comparisons are made
      between the two groups since they are not comparable. However, it is concluded in
      these two descriptive studies, that during these conditions, TPN does not prevent
      muscle protein catabolism either during basal conditions or after a minor
      surgical trauma such as laparoscopic cholecystectomy.

PMID- 10205341
TI  - Nutrition in adults with cystic fibrosis.
AB  - Improved survival has been associated with better nutritional status in patients
      with cystic fibrosis (CF). In this study we examined the relationship between
      nutritional state and other measures of clinical severity in adult patients with
      CF, attending a regional centre. Eighty-one patients (median age 21 years) were
      studied. Patients with CF were significantly under weight, compared to healthy
      individuals but were of similar height. Measurements of lung function, FEV1 and
      FVC were significantly related to body mass index. Lung function was poorer in
      patients with chronic pseudomonal infection but body weight and body mass index
      were not significantly different compared to those without such infection. In 53
      patients who were alive 4 years later, FEV1 had declined by -10.5 (2.1)% (P <
      0.001) but there was no significant change in body weight 1.5 (6.5) kgs. In 23
      patients who died or had lung transplantation the change from 1994 to the date of
      death or transplantation the FEV1 was reduced by -7.9 (11.2)% (P = 0.004) and
      body weight -2.8 (4.4) kgs (P < 0.01). In 12 patients who had supplemental
      enteral feeding, the median increase in body weight was 7|kgs over a period of 12
      months. This study confirms that young adult patients with CF are significantly
      under weight and declining health is associated with significant weight loss. In
      patients with severe malnutrition significant improvement can be achieved by
      enteral feeding.

PMID- 10205342
TI  - Precipitation of trace elements in parenteral nutrition mixtures.
AB  - Trace elements are an essential additive to parenteral nutrition (PN) mixtures.
      Previous studies have indicated that certain trace elements, in particular copper
      and iron, may interact with complete PN mixtures leading to precipitate
      formation. The causes of these incompatibilities have not been fully elucidated.
      The purpose of this study was to determine factors responsible for common trace
      element incompatibilities, using X-ray energy dispersive spectroscopy to examine
      the elemental content of precipitates isolated from stored PN mixtures with added
      trace elements. Results indicated that copper sulphide precipitated most rapidly
      in PN mixtures containing Vamin 9 and in mixtures stored in multilayered bags.
      Copper sulphide precipitation was delayed in PN mixtures containing Vamin 14 and
      was not observed in PN mixtures stored in EVA bags. Iron phosphate precipitates
      were observed in Synthamin-containing PN mixtures after storage, but this was
      prevented in mixtures containing vitamins stored in multilayered bags.

PMID- 10205343
TI  - Manganese requirement and toxicity in patients on home parenteral nutrition.
AB  - Two patients who were receiving home parenteral nutrition complained of vague
      neurological symptoms of such severity that they underwent full clinical
      appraisal. The only positive finding was that plasma manganese concentrations
      were greater than twice the upper 95% confidence interval of normal (7
      27|nmol/l). In the light of this result all nine patients receiving home
      parenteral nutrition underwent evaluation for possible manganese toxicity. One
      other patient had serum manganese concentrations exceeding twice the upper limit
      (127|nmol/l). The three patients with elevated serum Mn had evidence of manganese
      deposition in the brain on magnetic resonance imaging scanning. In contrast two
      patients with normal plasma results had negative scans. Patient susceptibility
      appears very variable. We suggest that current amounts of trace elements provided
      in nutrition solutions may be a potential source of nutrient activity. The fine
      tuning of supply and demand may be difficult on account of a limited range of
      commercially available trace element solutions.

PMID- 10205344
TI  - Stability of cocarboxylase in parenteral nutrition mixtures stored in multilayer
      bags.
AB  - The aim of this study was to determine the stability of cocarboxylase, a thiamine
      derivative employed as a vitamin B1 source in multivitamin additives, in
      parenteral nutrition (PN) mixtures containing different commercial amino acid
      infusions. In particular, the influence of a metabisulphite-containing amino acid
      product, Freamine III, was investigated. A liquid chromatographic assay method
      for cocarboxylase was developed and employed to investigate cocarboxylase
      degradation during extended storage of PN mixtures at 5 degrees C in multilayered
      bags. Results indicated that cocarboxylase was relatively stable over the 28-day
      storage period in PN mixtures containing Synthamin or Vamin products as amino
      acid source. In contrast, degradation was accelerated in PN mixtures containing
      Freamine III, suggesting that cocarboxylase is degraded by sodium metabisulphite,
      showing similar sensitivity to thiamine.

PMID- 10205345
TI  - Bibliographic information retrieval in the field of artificial nutrition.
AB  - The enormous amount of data available for clinical and research purposes has made
      information searching a complex task. We have designed a study to determine which
      bibliographic databases provide appropriate information for the field of
      artificial nutrition. Of the 149 databases consulted in the preliminary search,
      15 were found to contain an appreciable number of titles related to our field. As
      a general result, we found that MEDLINE had the largest number of titles but
      other databases oriented toward more specific topics contained references that
      were unique to them. The results show that an exhaustive search for any topic
      concerning artificial nutrition must be done on MEDLINE, EMBASE and Current
      Contents (75% productivity). These can be complemented with others according to
      their specialization in the subject to be treated. To obtain productivity over
      75%, from five to seven databases must be consulted, according to the item under
      study.

PMID- 10205346
TI  - Metabolic and nutritional consequences of chronic hypoxia.

PMID- 10205347
TI  - Energy expenditure during allogeneic and autologous bone marrow transplantation.
AB  - Resting energy expenditure (REE) was measured by indirect calorimetry during
      allogeneic and autologous bone marrow transplantation in order to evaluate the
      evolution in allogeneic and autologous recipient patients. REE values obtained
      with indirect calorimetry and compared with values using the Harris-Benedict
      formula were different. Evolution of REE during aplasia were significantly
      different in autologous and allogeneic recipients with an increase 11.5 ' 10.8
      cent for autologous and a decrease of - 7.3 ' 8.9 cent in allogeneic bone marrow
      transplantation (BMT) patients. There were no differences in nutritional status
      and REE before BMT, at discharge and 1 month after discharge between the two
      groups but all patients had inflicted damage on their nutritional status at
      discharge from hospital after BMT. However, these patients differed because of
      the decrease in oral nutritional intake and an increase in the length of aplasia
      and hospital stay in allogeneic patients. Currently, there is no proof that
      recommendations for nutritional interventions or results of nutritional
      investigations in allogeneic BMT can be extrapolated in autologous patients.
      Harris-Benedict formula does not estimate the energy expenditure of patients
      submitted to massive chemotherapy and BMT with enough precision because of the
      great differences in individuals.

PMID- 10205348
TI  - Effect of providing fortified meals and between-meal snacks on energy and protein
      intake of hospital patients.
AB  - This study aimed to evaluate whether food fortification and snacks could increase
      the energy and protein intakes of hospital patients. The control group of 82
      consecutive admissions on medical, elderly care and orthopaedic wards ate freely
      from the hospital menu. Subsequently, an intervention group of 62 patients were
      offered fortified food and snacks, providing an extra 22.2|g protein/day and 966
      kcal/day in addition to the standard menu. Fortification significantly increased
      energy intake in the intervention group (P = 0.007, independent samples t-test),
      having the greatest effect on groups with the lowest energy intake, that is male
      and female orthopaedic, female medical and female elderly patients (84 cent of
      total). The increases in energy intake were 21.3 cent, 21.4 cent, 23 cent and
      19.6 cent respectively. Although the increased energy and protein intake
      represented 25.6 cent and 22.5 cent respectively, of the supplements given, and
      suggested that wastage was high, it was nevertheless sufficient to remove energy
      deficit. We therefore propose that provision of fortified food and snacks is a
      convenient method of improving the nutritional intakes of hospital patients.

PMID- 10205349
TI  - Randomized controlled trial of gamma-linolenic acid and eicosapentaenoic acid in
      peripheral arterial disease.
AB  - BACKGROUND AND AIMS: epidemiological studies suggest polyunsaturated fatty acids
      protect against the development of atherosclerosis. The aim of this study was to
      perform a randomized controlled trial of gamma-linolenic and eicosapentaenoic
      acids in patients with lower limb atherosclerosis. Main outcome measures were:
      cholesterol and lipoprotein concentrations; haemostatic and rheological
      variables; the ankle brachial pressure index; walking distance; and
      cardiovascular events and death. METHODS: 120 men and women with stable
      intermittent claudication were randomized to 2 years treatment with either a
      combination of gamma-linolenic and eicosapentaenoic acids, or placebo. RESULTS:
      39 (65.0 cent) of those taking fatty acids and 36 (60.0 cent) of those taking
      placebo completed the trial. Lipid concentrations did not differ significantly
      during the trial. In those taking fatty acids, haematocrit was significantly
      higher than in the placebo group after 6 months (46.1 cent compared with 44.6
      cent, P </= 0.01), and systolic blood pressure was significantly lower after 2
      years (150|mmHg compared with 161.8|mmHg, </= 0.05). There was no difference in
      walking distance, but there was a small reduction in non-fatal coronary events in
      the fatty acid group (10 cent compared with 15 cent, P > 0.05). CONCLUSIONS: a
      combination of polyunsaturated fatty acids produced a statistically significant
      reduction in systolic blood pressure, but no other significant benefits on risk
      factors. The trend towards fewer coronary events in those taking fatty acids
      warrants further investigation.

PMID- 10205350
TI  - MCT/LCT emulsion ameliorate liver fat deposition in insulin-treated diabetic rats
      receiving total parenteral nutrition.
AB  - This study was designed to investigate the effects of high energy infusion and
      insulin treatment on plasma and liver lipids in diabetic rats receiving total
      parenteral nutrition (TPN). Diabetes was induced in rats by streptozotocin. The
      diabetic rats were assigned to two TPN groups to receive either long chain
      triglyceride (LCT) or medium chain triglyceride (MCT)/LCT (1:1) as a fat source.
      The TPN solutions were isonitrogenous, isocaloric and identical in nutrient
      composition except for the fat emulsion. All rats received the TPN solution at an
      energy level of 35|kcal/100|g of body weight. The LCT and MCT/LCT groups were
      further divided into two subgroups, depending on whether they were treated with
      insulin. The results demonstrated that, between the MCT/LCT and LCT groups, no
      differences were observed in body weight and nitrogen retention, as well as the
      concentrations of plasma glucose, nonesterified fatty acids, beta
      hydroxybutyrate, and total cholesterol. Diabetic TPN rats without insulin
      treatment had weight loss and negative nitrogen balance during the experiment.
      Diabetic TPN rats treated with insulin, however, demonstrated less weight loss
      and positive nitrogen retention. Insulin treated groups had significantly higher
      liver fat content than did those without insulin treatment. Furthermore, liver
      fat content was significantly higher in the LCT group than in the MCT/LCT group
      among insulin treated TPN rats. These results suggest that compared with the LCT
      emulsion, infusion of the MCT/LCT emulsion ameliorated liver fat deposition in
      insulin-treated diabetic rats receiving TPN.

PMID- 10205351
TI  - Rat serum alkaline phosphatase electrophoretic fractions: variations with
      feeding, starvation and cellulose fibre ingestion.
AB  - The effect of feeding, starvation and fibre ingestion on alkaline phosphatase
      (ALP) activity (E.C. 3.1.3.1) was studied in Wistar rat serum. Using identical
      assay conditions for total ALP activity determination and for electrophoretic ALP
      isoenzymes/fractions activity calculation, alpha- and beta-naphthyl phosphates
      and p-nitrophenyl phosphate were used as substrates and 2-amino-2-methyl-1
      propanol/HCI was used as buffer, respectively. Total activity with beta-naphthyl
      phosphate was significantly higher than with alpha-naphthyl phosphate and p
      nitrophenyl phosphate; with alpha-naphthyl phosphate it was significantly higher
      than with p-nitrophenyl phosphate. With all substrates, fed animals had
      significantly higher total activity than starving ones. Electrophoresis allowed
      the separation of two fractions. The second fraction activity was significantly
      higher in the fed group than in the starving ones, irrespective of the substrate
      used. Starving animals with fibre showed higher values of this fraction than
      starving animals without fibre, the difference reaching statistical significance
      with alpha-naphthyl phosphate. The first fraction predominated in both starved
      groups and the second in the fed group. The second fraction was identified as
      intestinal ALP. We conclude that the mechanical stimulation of the digestive
      tract appears to influence the passage of intestinal ALP to serum. The
      experimental conditions used enable quantification of electrophoretic fractions
      based on total activity. Activity depends on the substrate used.

PMID- 10205352
TI  - Pressure sores and tube feeding in patients with a fracture of the hip: a
      randomized clinical trial.
AB  - Pressure sores are a frequent problem, especially in elderly patients.
      Nutritional status may influence the incidence, progression and severity of
      pressure sores, data, however, are contradictory (1). The purpose of this study
      was to determine the effect of supplemental feeding on the nutritional status and
      the development and severity of pressure sores. The effect of supplemental
      feeding overnight (tube +) on patients with a fracture of the hip and a high
      pressure-sore risk score, was studied in a randomized clinical trial. The control
      group (tube -) had no supplemental feeding. After informed consent, 140 patients
      were randomized, and 129 of these took part in the trial (62 tube +, and 67 tube 
      ). Protein and energy intake, haemoglobin, serum albumin, total serum protein and
      pressure-sore grade were measured at admission and after 1 and 2 weeks. Of the 62
      patients randomized for tube feeding (tube +), only 25 tolerated their tube for
      more than 1 week and 16 for 2 weeks. Nevertheless, energy and protein intake was
      significantly higher in the tube + group (P < 0.001). This, however, did not
      significantly influence total serum protein, serum albumin and development and
      severity of pressure sores after 1 and 2 weeks. Comparison of the actually tube
      fed group (n=25 at 1 week, n = 16 at 2 weeks) and the control group showed a 2-3
      times higher protein and energy intake (P < 0.0001), and a significantly higher
      total serum protein and serum albumin after 1 and 2 weeks in the actually tube
      fed group (all P < 0.001). Pressure-sore development and severity were not
      significantly influenced in the actually tube fed group. We conclude that we were
      not able to show a significant decrease in development and severity of pressure
      sores, because the nasogastric tube for supplemental feeding was not well
      tolerated in this patient group. Nevertheless, tube feeding overnight does result
      in a significant higher protein and energy intake, and has a significant effect
      on nutritional status in the actually tube-fed group. Other means of supplemental
      feeding will have to be used in order to answer the question of whether
      supplemental feeding can decrease development and severity of pressure sores.

PMID- 10205353
TI  - Nutritional hepatic steatosis and mortality after burn injury in rats.
AB  - AIMS: To investigate the effects of diet composition and starvation on hepatic
      steatosis and mortality after severe burn injury in rats. METHODS: Experiment 1:
      rats received either normal chow (55 cent of energy carbohydrates, 14 cent fat,
      31 cent protein), a high-fat (40 cent carbohydrates, 40 cent fat, 20 cent
      protein), or a high-carbohydrate diet (81 cent carbohydrates, 4 cent fat, 15 cent
      protein) ad libitum for 6 days. Another three groups received these diets ad
      libitum for 6 days after 48|h starvation. Experiment 2: mortality after 60 cent
      total body surface area scald burn was determined in a control group of rats and
      a group with nutritionally induced hepatic steatosis. Hepatic steatosis was
      induced by feeding the rats a high-fat diet (40 cent carbohydrates, 4 cent fat,
      15 cent protein) ad libitum for 6 days. RESULTS: Without starvation, liver
      triglyceride content (mg/g liver) increased in response to the high-fat diet
      (25.6'6.9) compared to normal chow (9.4'3.8; P < 0. 05); the high-carbohydrate
      diet had no influence on liver triglyceride content (12.4'3.7). Refeeding after
      starvation resulted in elevated (P < 0.05) liver triglyceride content in the high
      fat (18.8'8.3) and the high-carbohydrate group (28.7'14.4 vs control 6. 7'3.7).
      Liver triglyceride content correlated (R2=0.72; P < 0.05) to non-protein energy
      intake but not to total energy intake. Burn caused 33 cent mortality in the
      hepatic steatosis group and no deaths in the control group (P < 0.05).
      CONCLUSIONS: Diet composition and preceding starvation independently manipulate
      hepatic fat content in rats. Hepatic steatosis increases mortality after burn
      injury. Thus, nutritional interventions to reduce hepatic fat accumulation may be
      beneficial.

PMID- 10205354
TI  - Consensus Roundtable on Nutrition Support of Tube-Fed Patients with Diabetes, 28
      February-1 March, 1998, Chicago, Illinois, USA. Introduction.

PMID- 10205355
TI  - Glucose control guidelines: current concepts.
AB  - The Diabetes Control and Complications Trial (DCCT) ended decades of controversy
      regarding the necessity of tight glycemic control for type 1 diabetes by
      demonstrating that glucose control using intensive insulin therapy significantly
      reduced long-term microvascular complications. The American Diabetes Association
      (ADA) guidelines empirically support the same goal of attempting to obtain
      normoglycemia in patients with type 2 disease; however, unlike in type 1 disease,
      insulin is a tertiary option, following diet, exercise, and oral agents. Emerging
      long-term intervention data in type 2 diabetes suggest that insulin may pose
      increased cardiovascular risk in this already 'at-risk' population. However, many
      type 2 diabetics will eventually require insulin. Clearly, more studies are
      warranted to assess the risks, benefits, and feasibility of improved glycemic
      control in type 2 diabetes. Nonetheless, two principles are clear. First,
      promoting blood glucose levels approaching normoglycemia is an important factor
      in preventing long-term microvascular complications. Second, type 2 diabetes
      comprises numerous metabolic conditions; therefore an integrated effort by the
      patient and healthcare team is required to optimize blood glucose and serum lipid
      levels and minimize cardiovascular risk factors.

PMID- 10205356
TI  - Nutrition recommendations for the person with diabetes.

PMID- 10205357
TI  - Rationale for specialized nutrition support for hyperglycemic patients.

PMID- 10205358
TI  - Effect of high-carbohydrate versus high-monounsaturated fatty acid diet on
      metabolic control in diabetes and hyperglycemic patients.

PMID- 10205360
TI  - The dietitian's perspective: nutrition care for patients with diabetes requiring
      nutrition support.

PMID- 10205359
TI  - Clinical experience with modified enteral formulas for patients with diabetes.
AB  - Standard tube-feeding formulas may not meet the specific nutritional needs of
      many patients with impaired glucose tolerance. In particular, standard enteral
      formulas often cause potentially dangerous increases in blood glucose levels.
      Clinical experience and studies to date have shown advantages of using disease
      specific enteral formulas for these patients. Specialized formulas with increased
      fiber may improve glycemic control, although the concomitant increases in
      viscosity of these formulas may limit their usefulness for tube feeding.
      Glucerna, a specialized formula with low-carbohydrate, high-monounsaturated-fat
      content that has been enriched with a fiber source that permits tube feeding, has
      been shown to improve glycemic control and decrease the potential for
      complications. Appropriate tube feeding for patients with impaired glucose
      tolerance, however, extends beyond formula composition. Patients also require
      ongoing blood glucose monitoring, evaluation of gastric motility, and assessment
      of overall health and nutritional status.

PMID- 10205361
TI  - Quality of life in tube-fed patients with diabetes mellitus.

PMID- 10205362
TI  - Consensus Roundtable on Nutrition Support of Tube-Fed Patients with Diabetes.
      Consensus statement.

PMID- 10205364
TI  - Injuries in adolescent workers. Health promotion and primary prevention.
AB  - 1. Adolescent workers experience significant morbidity and mortality. Specific
      characteristics and lifestyle issues of adolescents increase their susceptibility
      to injury and illness. 2. Occupational and environmental health nurses need to
      advocate for improved legislation to protect children and adolescents and to
      develop better data collection and surveillance. 3. Occupational and
      environmental health nurses must bring awareness of the specific concerns for
      adolescent workers and developmentally appropriate injury prevention strategies
      to the community, industry, and labor groups. 4. Nurses in the workplace can
      become involved in STW programs and CLWT projects and provide impetus for
      promoting a comprehensive approach that recognizes the unique characteristics of
      adolescents, their health promotion needs, and their need to recognize and avoid
      hazards.

PMID- 10205365
TI  - Injuries from construction falls. Functional limitations and return to work.
AB  - Finding a measure that distinguishes well between the severity levels of less
      serious injuries such as those found in occupational settings has been
      problematic. In this study of 255 construction workers who sustained nonfatal
      falls at work, two measures of injury severity were used--the Injury Severity
      Score (ISS) and the disability index of the Stanford Health Assessment
      Questionnaire (HAQ), a functional limitation measure. The HAQ scores were more
      normally distributed than the ISS and provided useful information about the
      degree to which workers were disabled from falls during their first week of
      recovery. The mean HAQ score was 1.46 (SD = 0.75) on a scale of 0 to 3, with
      higher numbers representing more limited functioning. With regard to individual
      tasks, participants reported having the most difficulty performing heavy chores
      (mean = 1.89; SD = 1.02), dressing themselves (mean = 1.54; SD = 1.05), and
      bending to pick up clothing from the floor (mean = 1.40; SD = 1.02). The HAQ
      scores were significantly and moderately correlated with days lost from work (r =
      .52; p < .001). Unexpectedly, 97 workers reported that they were able to return
      to light or modified duty following their falls.

PMID- 10205366
TI  - Client satisfaction with nursing services. Evaluation in an occupational health
      setting.
AB  - Client satisfaction surveys have served as a valued appraisal tool of quality
      nursing care in various health care settings, but there is a paucity of published
      research using these tools in the occupational health setting. Employing a
      modified version of the SERVQUAL questionnaire, this study identified employees'
      current levels of satisfaction and perceived importance of nursing care provided
      by an occupational health program. Two hundred randomly selected employees were
      asked to participate by completing the survey, with 86 (43%) responding. Results
      indicated a positive correlation between client satisfaction and perceived
      importance of nursing care. Moderately high levels of client satisfaction existed
      in the sample. The use of client satisfaction surveys based on the strength of
      client preferences could identify areas of health care that need improvement.

PMID- 10205367
TI  - Chemical eye injuries in the workplace. Prevention and management.
AB  - 1. The majority of ocular burns are related to accidents at work. Acute ocular
      chemical injuries require emergent recognition and management. 2. Copious
      irrigation of the eye, done immediately at the scene, is the most important
      factor in the long term prognosis of ocular chemical burns. 3. After irrigation
      has been completed and the eyes have been allowed to rest, visual acuity can be
      tested and referrals can be made to health care facilities and an
      ophthalmologist. 4. The nurse conducts health hazard assessments of the
      workplace, provides information about workplace chemicals and their risks, and
      ensures proper safety protective equipment and emergency supplies. Practicing
      emergency procedures such as irrigation is important. 5. The nurse monitors and
      analyzes injury exposure episodes and trends, along with coordinating referrals,
      treatments, and follow up care for workers with ocular chemical burns.

PMID- 10205368
TI  - Contracting for occupational health services: Part 1--Preparing an effective
      request for proposal.

PMID- 10205369
TI  - AAOHN advisory: nurse practitioners in occupational and environmental health.

PMID- 10205370
TI  - Occupational hazard exposure and at risk drinking.
AB  - This study examined associations between workers' reported exposure to
      occupational hazards and at risk drinking. A sample of 15,907 working adults was
      drawn from the 1985 National Health Interview Survey (NHIS) (weighted sample
      represented 85,395,000 workers). This was the only year the NHIS included
      questions on both occupational hazard exposure and at risk drinking. Occupational
      hazard exposures included chemical/biological substances, physical hazards,
      injury risk, and mental stress. At risk drinking was defined as binge drinking
      and drinking and driving. Prevalence adjusted odds ratios were estimated. Sixty
      percent of workers reported exposure to one or more occupational hazards with
      considerable variation among and within occupations. In all, 31% reported binge
      drinking and 15% drove after drinking too much. In a multivariate analysis that
      controlled for background characteristics, workers who reported occupational
      hazard exposures were 1.2 to 1.4 times more likely to engage in binge drinking
      than workers without exposures. Similar results were found for drinking/driving.
      All multivariate results were statistically significant. Findings suggest workers
      who report occupational hazard exposures are at greater risk of both binge
      drinking and drinking/driving. Occupational and environmental health nurses can
      lead workplace initiatives to reduce occupational hazard exposure and,
      simultaneously, invest in health promotion efforts to curb at risk drinking among
      workers.

PMID- 10205371
TI  - Managing chronic fatigue syndrome: overview and case study.
AB  - 1. The basic principles of envelope theory are explained. By not overexerting
      themselves, people with CFS can avoid the setbacks and relapses that commonly
      occur in response to overexertion while increasing their tolerance to activity.
      2. By collecting time series data on fluctuations in energy levels, important
      clinical observations can be made in respect to a client's unique condition and
      experience with CFS.

PMID- 10205372
TI  - Perceived psychological stress and upper extremity cumulative trauma disorders.
AB  - This report presents data exploring the relationship between perceived
      psychological stress and several variables implicated in the etiology of upper
      extremity cumulative trauma disorders (UECTDs). The sample was 354 workers from
      three different manufacturing companies. The primary job exposure for the
      subjects was that they were engaged in jobs that involved repetitious movements
      of the upper extremities, primarily of the hands and arms. Data collection
      included a detailed health history, a comprehensive physical examination of the
      upper extremities, limited electrodiagnostic testing, Cohen's Perceived Stress
      Scale, Karasek's Job Content Questionnaire, demographic information, and a
      measurement of repetition. Descriptive analyses, analysis of variance,
      correlational analyses, and multiple linear regression were used to examine the
      data. Perceived stress, as measured in this study, was only weakly associated
      with repetition, job dissatisfaction, and subjective complaints related to
      UECTDs. In addition, factors generally accepted as related to UECTDs (e.g.,
      repetition, female gender, hormonal influences, and existing medical conditions)
      were not robust predictors of perceived stress. The major limitation is related
      to the measurement of perceived psychological stress. Like most psychosocial
      phenomena, perceived stress is a complex construct, one that is difficult to
      measure and correlate with health outcomes. Further research is necessary to
      examine what role, if any, perceived stress may have in the etiology of UECTDs.

PMID- 10205373
TI  - Adult education: helping adults begin the process of learning.
AB  - As adult educators, occupational and environmental health nurses plan, implement,
      and evaluate health education to meet the needs of employees. The nurse is in the
      unique position of understanding health principles, knowing the target
      population, understanding the work environment, and operationalizing adult
      education strategies and techniques. By using the principles of adult education
      as well as understanding the motivation of learners, the nurse in the workplace
      is more successful in helping adults obtain their health care goals.

PMID- 10205374
TI  - Prevention and management of acute renal failure.
AB  - Acute renal failure (ARF) is estimated to occur in 5% of all hospitalised
      patients. It is therefore valuable to be familiar with the potential causes of
      ARF and to be able to identify patients who are at particular risk of developing
      ARF. This Clinical Update will indicate how establishing routine preventative
      strategies may be the most effective way to reduce the high mortality and
      morbidity associated with ARF.

PMID- 10205375
TI  - Skill shortages.

PMID- 10205376
TI  - ANJ interviews industrial relations. Interview by John Moran.

PMID- 10205377
TI  - ANJ interviews healthcare. Interview by John Moran.

PMID- 10205378
TI  - Nurses and the brave New World.

PMID- 10205379
TI  - Job sharing.

PMID- 10205381
TI  - In the best interest of the child.

PMID- 10205380
TI  - Work and Death in Siberia. Interview by Dimitri Serghis.

PMID- 10205382
TI  - Quality in perspective.
AB  - Quality and accreditation have taken great strides in recent years. If you are
      one of the many who find the subject confusing then blame the relentless changes
      in concepts and terminology that swept into health care. To put this in
      perspective, I will look at where we have been, where we are, and where we are
      headed.

PMID- 10205383
TI  - ANJ interviews superannuation reform. Interview by John Moran.

PMID- 10205384
TI  - Measuring health outcomes.

PMID- 10205385
TI  - A war remembered. Interview by Heather Witham.

PMID- 10205387
TI  - The power to prescribe.

PMID- 10205386
TI  - Maximising the use of the nursing workforce.

PMID- 10205388
TI  - Making sense of changes to aged care.

PMID- 10205389
TI  - The Howard tax reforms and health care.

PMID- 10205390
TI  - From nursing home to parliament. Interview by Heather Witham.

PMID- 10205391
TI  - Why hospital privatisation is bad for patients and nurses.

PMID- 10205392
TI  - Credentialling. Do Australian nurses need it?

PMID- 10205393
TI  - Two Australian coronial reports concerned with the diagnosis, treatment and
      admission of children to hospital.

PMID- 10205394
TI  - Children are not little adults.
AB  - Children differ from adults in more than just size. Understanding the
      physiological differences between children and adults can assist in evaluating a
      child and documenting your care.

PMID- 10205396
TI  - Keeping patients in the pink.

PMID- 10205395
TI  - Paediatric pain management.
AB  - Paediatric pain management has experienced enormous change over the past 15
      years. The early work carried out by Schecter dispelled the myths surrounding
      children and pain leaving the way clear for the pursuit of innovative methods of
      assessment, treatment and evaluation.

PMID- 10205397
TI  - Rejecting the language of 'us and them'.

PMID- 10205398
TI  - Recruitment and retention in perioperative nursing.

PMID- 10205399
TI  - Paediatrics and medication administration. Some practical issues.
AB  - Promotion of safe administration of medication to children can be enhanced by
      expanding pharmacokinetics in paediatric practice. The absorption, distraction
      metabolism and excretion of medications vary with the developmental changes that
      accompany a child's growth. Application of paediatric pharmacokinetics to nursing
      practice when administering medications to children promotes safety in practice.

PMID- 10205400
TI  - The health of a tiny nation.

PMID- 10205401
TI  - Asthma clinics in general practice: the educator's perspective.

PMID- 10205402
TI  - Credentialling. In whose interests?

PMID- 10205403
TI  - Failure to warn or 'informed consent' cases.

PMID- 10205404
TI  - Targetting primary research: using an evidence-based approach.

PMID- 10205405
TI  - Principles of traction.
AB  - Traction has been the mainstay of orthopaedic management for thousands of years,
      with its use recorded by the Aztecs and ancient Egyptians. In more recent times,
      however, the advances in surgical reductions of fractures and muscutoskeletal
      disruptions, coupled with the economic imperatives of reducing hospital bed stay
      days has seen a reduction the use of prolonged periods of traction.

PMID- 10205406
TI  - Flight nurses are the backbone of the Royal Flying Doctor Service and must be
      prepared for anything. Interview by Dimitri Serghis.

PMID- 10205407
TI  - Life after life-support.

PMID- 10205408
TI  - The common law obligation of an employer to establish, maintain and enforce a
      safe system of work.

PMID- 10205409
TI  - Spirited approaches.

PMID- 10205411
TI  - Penetration of complementary therapies into NHS trust and private hospital
      practice.

PMID- 10205410
TI  - 'Just the ticket': integrating massage and reflexology in practice (Part I).
AB  - The purpose of these papers is to describe and discuss the piloting and
      evaluation of an inpatient complementary therapy service. This was a single site
      case study without a control group and involving practitioners themselves
      collecting data, recording reflections on their own practice and engaging in
      monthly clinical supervision sessions. The service was aimed at providing
      treatments of hand and foot massage incorporating reflexology techniques for a
      total of 18 patients. In part 2 of this paper, an evaluation of the project will
      be presented including the findings of this pilot service from the perspective of
      both the patients and practitioners, and the analysis of some of the
      physiological data collected. Part 3 will focus on a subgroup of the patient
      cohort to illuminate the experience from both patient and practitioner
      perspective.

PMID- 10205412
TI  - Teresa Hsu: living to a full, young age. Interview by Jenni Nelson.

PMID- 10205413
TI  - Taking the stress out of managing stress! Living with ease.

PMID- 10205414
TI  - "We value cultural diversity"--the schizophrenic message in health care.

PMID- 10205415
TI  - The mental health of homeless school-age children.
AB  - PROBLEM: The mental health of homeless school-age children. METHODS: A
      convenience sample of 46 homeless children between the ages of 8 and 12 years
      completed the Children's Depression Inventory (CDI) and each child's mother
      completed the Child Behavior Checklist (CBCL). FINDINGS: Fifty-seven percent of
      the children had depressive symptoms and 26% needed additional evaluation for
      mental health problems. Overall, the CDI and CBCL scores indicated that gender or
      ethnicity are not related to the children's mental health. CONCLUSIONS: The
      mental health of homeless schoolage children should be assessed, as they may be
      at risk for mental health problems.

PMID- 10205416
TI  - Milieu management of traumatized youngsters.
AB  - TOPIC: Traumatized youngsters are disproportionately represented in out-of-home
      treatment facilities. Conceptual models that guide treatment of traumatized
      youngsters are not well integrated with models that guide milieu management.
      PURPOSE: To describe a milieu management approach for treatment of traumatized
      youngsters. SOURCES: Clinical experience with hospital and residential treatment
      facilities and therapeutic foster homes, as well as literature support.
      CONCLUSIONS: Familiar treatment strategies take on an additional meaning when
      they are implemented in the context of the children's histories of exposure to
      traumatic events.

PMID- 10205417
TI  - Parent education: an evaluation of STEP on abusive parents' perceptions and abuse
      potential.
AB  - PROBLEM: To examine the effects of a structured, time-limited parent training
      group on abusive or potentially abusive parents. METHODS: A pretest-posttest
      control group design was used with consenting parents (N = 18) to examine the
      effects of Systematic Training for Effective Parenting (STEP) on abusive parents'
      perceptions of their children's behaviors and on the parents' potential to
      physically abuse. The Adlerian Parental Assessment of Child Behavior Scale and
      the Child Abuse Potential Inventory were used to measure treatment effects.
      FINDINGS: After participating in STEP, abusive parents had significantly more
      positive perceptions of their children and were significantly less potentially
      abusive. Using volunteers, the project cost an average of $100 for each parent.
      CONCLUSIONS: The research lends empirical support to individual psychology and
      family systems theory. Future research is indicated using larger samples to
      examine lay vs. professional leadership of the groups, as well as comparisons of
      different parenting programs with abusive parents.

PMID- 10205418
TI  - Moments of excellence. Nurses' response to role redesign in long-term care.

PMID- 10205419
TI  - Interventions for disruptive behaviors. Use and success.
AB  - Health care providers deal with disruptions from geriatric patients routinely.
      Despite the negative impact on provider efficiency, provider-patient relations,
      and patient well-being, there have been no systematic clinical studies of the
      impact of disruptive behaviors on geriatric inpatient care. This article presents
      a taxonomy for these behaviors, applying them to a study of disruptive behaviors
      and concomitant nursing interventions on a geriatric evaluation and management
      (GEM) unit. The sample, consisting of 23 nursing staff (16 RNs, 4 LPNs, and 3
      nurse aides), was followed over 8 weeks (five shifts per week, distributed
      randomly over day, evening, and night shifts). An experienced pair of RN
      observers logged all disruptive behaviors and the associated interventions
      employed by the nursing providers. The taxonomy was validated on 97 disruptive
      events (113 disruptive behaviors) initiated by 87 patients. The major findings of
      the study were: (a) disruptive behaviors are common on a GEM unit; (b) behaviors
      that disrupt care are recognized only 50% of the time by nursing staff; (c)
      interventions, when used singly, were found successful 45% of the time; (d)
      multiple simultaneous interventions may be more successful than single
      interventions but were used in only 16% of cases; and (e) selection of
      interventions may be associated with staff education level.

PMID- 10205420
TI  - Respite for caregivers. A community-based model in a rural setting.
AB  - Currently in the United States, 4 million Americans suffer from Alzheimer's
      disease (AD), and projections are that this population will increase to 7 million
      by the year 2040. Traditionally, care for these clients is provided by family,
      relatives, and friends--an informal caregiver network (ICN). Changing
      demographics in the United States are threatening this caring network. When these
      factors are coupled with the recent emphasis on cost containment in health care,
      caring for this client population has become a significant political, economic,
      and societal issue. Strategies must be developed to meet the needs of both the
      clients and their caregivers. Respite services have been identified as an
      effective strategy in the ongoing management of clients with AD. A model is
      proposed to provide community-based respite services in a rural setting in
      northeast Georgia. The need for respite services, along with barriers to the use
      of such services by clients and their caregivers, is described. Strategies to
      overcome barriers and provide needed services in a cost effective and sensitive
      manner are presented. Implications for nursing and related disciplines are
      discussed.

PMID- 10205421
TI  - Preventing cascade iatrogenesis in hospitalized elders. An important role for
      nurses.

PMID- 10205422
TI  - Test of an educational brochure on advance directives designed for well-elderly
      people.
AB  - The aim of this study was to test an advance directive brochure designed
      especially for well-elderly people. The brochure was developed using information
      from literature on preparing educational materials and from information gained
      from well-elderly focus groups. The information sought was in regard to what they
      knew and what they wanted to know about advance directives and what they found
      appealing in brochures on advance directives. Twenty well-elderly people
      participated in the study. Prior to data collection, the brochure was given to 10
      nurses who were asked to evaluate it according to the Bernier Instructional
      Design Scale 2. Out of a possible 280 points, the brochure received 244. The
      participants in the study were asked to read the brochure and answer 15 questions
      about the content, user friendliness, and attractiveness of the brochure. The
      overall results were positive. The first five questions had to do with the
      appearance of the brochure. All 20 participants responded favorably to these
      questions. The next 10 questions had to do with understanding the content. A
      simple percentage was used to calculate the results. The participants understood
      90.5% of the content. Based on these results, the brochure should be used in
      future intervention research and in discussions regarding the education of well
      elderly people and the drafting of advance directives.

PMID- 10205423
TI  - Meal management strategies of older adult women.

PMID- 10205424
TI  - Betty and Jean.

PMID- 10205425
TI  - The "Bellagio consensus": ten years later.

PMID- 10205426
TI  - Bilirubin status as an outcome measure in monitoring adherence to baby-friendly
      breastfeeding policies in hospitals and birthing centers in the United States.

PMID- 10205427
TI  - Policy considerations for the introduction and promotion of the lactational
      amenorrhea method: advantages and disadvantages of LAM.
AB  - Some attributes of LAM are unquestionably positive, such as the fact that it is
      effective. Clinical trials of LAM have upheld the Bellagio Consensus that the
      chance of pregnancy is less than 2% in the first 6 months postpartum in
      amenorrheic women who are fully or nearly fully breastfeeding. Secondary data
      analyses in numerous settings have drawn the same conclusion. Whether as a
      strategy or a method, used correctly or even if used imperfectly, LAM is a
      reliable way to avoid pregnancy. To the extent that LAM represents an additional
      contraceptive option, this is also clearly positive since a broad array of
      contraceptive options maximizes the likelihood of finding a good fit between user
      and method, and increases contraceptive use. Other characteristics of LAM
      represent potentially positive impacts. If LAM is shown to be an effective
      conduit to other modern methods, the implications are profoundly positive. If LAM
      is cost effective, for households and/or for programs, this will also make the
      method extraordinarily attractive. Conversely, some aspects of LAM are negative,
      such as the fact that it affords no protection against STDs, it requires
      counseling from a well-informed provider, and intensive breastfeeding can make
      heavy demands on the woman's time. Many of the remaining attributes of LAM may
      not be important to a policy decision about LAM promotion. For example, whether
      LAM is actualized as a strategy or a method may not be important to a decision to
      promote LAM, although it has a huge impact on how services are delivered. Some
      factors may be profound on a local or individual level. For example, one simple
      factor, such as the absence of full/nearly full breastfeeding, can rule out the
      method as an option, while another, such as the fact that it provides the needed
      waiting period during vasectomy counseling, can make LAM the method of choice.
      Although LAM seems unlikely to have widespread popularity in societies like the
      United States, within such settings are breastfeeding women for whom other
      contraceptive choices are not satisfactory and to whom LAM is attractive.
      Although clinicians cannot be expected to directly provide LAM education in every
      setting, women should be informed about LAM as an effective contraceptive choice,
      and clinicians should be prepared to make referrals to competent sources. The
      future of LAM, especially in terms of formal, programmatic initiatives, may
      continue to be focussed in transitional and less developed settings. Comparative
      cost/benefit analyses for both the family planning program and the household will
      contribute meaningfully to decisions about whether to use LAM and whether to
      include LAM in national and local family planning policies and programs. The most
      important call to action is to implement operations research designed to
      determine what factors, if any, will maximize the uptake of a second modern
      contraceptive method after LAM protection expires among never-users of family
      planning, to compare this with other contraceptive strategies, and to evaluate
      the cost aspects. If the potential of LAM to be a conduit to other modern
      contraceptive methods is effectively realized, the method can be profoundly
      important in the development of communities and in family formation. Because LAM
      is effective in preventing pregnancies, and because it extends the range of
      contraceptive choices, considering LAM on the policy level is always appropriate.
      Despite the array of drawbacks to LAM, as with any other family planning method,
      the potential assets of LAM, especially the promise to introduce nonusers to
      contraception, are sufficiently important to warrant the introduction of LAM
      within an operations research framework to both capitalize on its intrinsic
      strengths and determine its programmatic robustness. In the 10 years since the
      concept of LAM was pronounced as the Bellagio Consensus, claims have been made
      both for and against its use. During this time, program and policy leaders have
      been giv

PMID- 10205428
TI  - Hydrogel dressings not to be used on infected tissue.

PMID- 10205429
TI  - Risk factors for lactation mastitis.

PMID- 10205430
TI  - Breastfeeding the baby with congenital heart disease.

PMID- 10205431
TI  - Well-being of a baby breast fed by her mother on carbimazol treatment.

PMID- 10205432
TI  - Contamination in expressed breast milk.

PMID- 10205434
TI  - Maternal fatigue in breastfeeding primiparae during the first nine weeks
      postpartum.
AB  - This pilot study documented maternal fatigue levels and patterns among
      breastfeeding primiparae; relationships between maternal fatigue and select
      physiological, psychological, situational, and performance factors; and fatigue
      interference with activities of daily living. A convenience sample of 41 mothers
      completed self-report instruments measuring breastfeeding experiences, fatigue,
      sleep characteristics, perceived stress, depression, and infant temperament at 3
      days, 3, 6, and 9 weeks postpartum. Positive moderate relationships were detected
      at all four times for: breastfeeding problem severity (r = .38-.66, p < .05),
      depression (r = .45-.71, p < .01), and perceived stress (r = .36-.70, p < .05).
      Maternal sleep disturbance (r = .40-.54, p < .05) and/or effectiveness (r = -.33
      .45, p < .05) correlated with fatigue at each time period. Infant difficulty was
      positively and mildly related to fatigue at 6 and 9 weeks (r = .32-.43, p < .05).
      Maternal age correlated positively and moderately to fatigue (r = .31-.50, p <
      .05). Finally, the impact of fatigue on activities of daily living and maternal
      role activities was low and nonsignificant. Results suggest fatigue is moderately
      significant to breastfeeding primiparae in the early to late postpartum period.

PMID- 10205435
TI  - Effects of cabbage leaf extract on breast engorgement.
AB  - The effectiveness of cabbage leaf extract was compared with that of a placebo in
      treating breast engorgement in lactating women. In a double-blind experiment with
      a pretest/posttest design, 21 participants received a cream containing cabbage
      leaf extract, while 18 received placebo cream. The placebo group received equal
      relief to the treated group, with the two groups showing no difference on all
      outcome measures. However, mothers perceived both creams to be effective in
      relieving discomfort. Feeding had a greater effect than the application of cream
      on relieving discomfort and decreasing tissue hardness. It is therefore
      recommended that lactation consultants encourage mothers to breastfeed if
      possible to relieve the discomfort of breast engorgement.

PMID- 10205436
TI  - The effect of fish consumption on DDT and DDE levels in breast milk among
      Hispanic immigrants.
AB  - A study was conducted to (1) determine the concentration of DDT/DDE in the breast
      milk of mothers residing in the Yakima river basin (WA, USA), (2) assess the
      relative impact of fish consumption on the total DDT/DDE body burden, and (3)
      determine if the amount of DDT/DDE received by their breastfed infants exceeds
      levels that could produce deleterious effects. Results indicate that fish
      consumption did not significantly increase DDT/DDE breast milk concentrations.
      Subjects born in Mexico had elevated levels of DDT/DDE in breast milk compared to
      levels found in US born subjects regardless of fish consumption. Infant daily
      intake levels for the various subject groups were determined and compared to
      acceptable and tolerable daily intake levels. With benefits of breast milk well
      understood, breastfeeding should still be strongly recommended for these mothers.

PMID- 10205433
TI  - Users' understanding of the lactational amenorrhea method and the occurrence of
      pregnancy.
AB  - It is unknown whether a user's understanding of the Lactational Amenorrhea Method
      (LAM) is related to its successful use. A study of 876 LAM users in Pakistan and
      the Philippines collected information about women's understanding of LAM. The
      present analysis aims to determine: (1) the proportion of LAM users who
      understand the method, (2) whether any known factors can distinguish those who
      understand LAM from those who do not, and (3) whether an understanding of LAM is
      related to subsequent pregnancy. Over 75% of LAM users could consistently recite
      the LAM guidelines correctly for a full year postpartum. However, 38% of users
      failed to display, at least once, an understanding of LAM during the first year
      postpartum mainly by failing to abstain, to use another method or to explain
      their nonuse of another method when their LAM protection expired. LAM
      understanding generally could not be predicted by sociodemographic factors. The
      occurrence of pregnancy during the first year postpartum was not related to LAM
      understanding, regardless of how LAM understanding was defined, nor could it be
      predicted by any other measured characteristic of the users.

PMID- 10205438
TI  - How should supplements be provided to the breastfed infant?

PMID- 10205437
TI  - Breastfeeding anaphylaxis case study.
AB  - This case describes a woman who experienced an anaphylatic reaction associated
      with breastfeeding. The reaction occurred with each feeding on day three
      postpartum and resolved on day four. Possible reasons for this severe reaction
      are suggested.

PMID- 10205440
TI  - Cost savings through the use of donor milk: case histories.

PMID- 10205439
TI  - Workplace lactation support, Part I: A return-to-work breastfeeding assessment
      tool.
AB  - As health professionals with expertise in the physiological and social aspects of
      breastfeeding, lactation consultants are in a unique position to help new mothers
      succeed at combining breastfeeding and employment. This involves helping women
      address logistical and interpersonal issues in the workplace as well as the
      mechanics of safe pumping and storage of breast milk. This article describes a
      return-to-work breastfeeding assessment tool designed to help lactation
      consultants evaluate clients' workplace lactation support. It also offers
      suggestions for use of this tool and other exercises to help new mothers
      negotiate the time, space and workplace support necessary to continue nursing
      upon return to work. The second part of this series addresses how lactation
      consultants can work with employers to support workplace lactation.

PMID- 10205441
TI  - Gastrointestinal medications and breastfeeding.
AB  - Medications used to treat gastrointestinal symptoms are increasingly being used
      as more have been gained nonprescription status. Most of the gastrointestinal
      medications, such as laxatives, antacids, and antidiarrheal agents, are used
      short term. Women who breastfeed should be aware of the risks of taking any
      medications, whether prescription or nonprescription. There is little information
      describing transfer into breast milk for many of these products. Cimetidine,
      atropine, cascara, cisapride, loperamide, magnesium sulfate, and senna are the
      only products identified by the AAP as compatible with breast feeding.
      Metoclopramide is listed by the AAP as a drug whose effect on nursing infants is
      unknown but may be of potential concern, although studies published to date have
      not reported any adverse effects. The safest laxatives and antidiarrheals are
      those that are not absorbed and should be considered first-line therapy for
      conditions of constipation or loose stools. Famotidine and nizatidine are
      excreted into breast milk to a lesser extent than cimetidine or ranitidine and
      may be the preferred histamine antagonists. Despite the limited data on the use
      of cisapride in nursing women, it is considered safe by the AAP and may be
      preferred over metoclopramide for first-line prescription treatment of heartburn.
      Although most of these agents appear safe in the nursing infant, caretakers
      should be aware of the potential adverse reactions that may occur in infants
      whose mothers require these products.

PMID- 10205442
TI  - Recent references.

PMID- 10205443
TI  - Closet consulting and other enabling behaviors.

PMID- 10205445
TI  - Extreme weight loss in the breastfed newborn.

PMID- 10205444
TI  - Supporting breastfeeding: a successful experience.

PMID- 10205446
TI  - Postpartum hypothyroidism.

PMID- 10205447
TI  - Staff support for mothers to provide breast milk in pediatric hospitals and
      neonatal units.
AB  - This paper reports on two surveys of nurses and midwives working in a large
      pediatric hospital and three neonatal units in London, England, regarding support
      for mothers to provide breast milk. One hundred and twenty-two pediatric staff
      and 55 neonatal staff returned the questionnaires. Fifty-three percent of
      pediatric staff had received no training in breastfeeding during or after nursing
      school. Twenty-two percent of neonatal staff had no relevant training, yet they
      frequently were asked to help mothers in providing breast milk for their infant.
      Some respondents demonstrated lack of relevant knowledge including the importance
      of breast milk, ideal frequencies for milk expression, and the potential to
      establish lactation at any time. There was a wide range of comments on the
      barriers in providing breast milk. These results illustrate the need for
      appropriate breastfeeding policies and staff training. There is a particular lack
      of studies based in the United Kingdom on breastfeeding in pediatric units. It is
      hoped that this article will generate discussion among staff about the
      breastfeeding support they offer and ways to strengthen it.

PMID- 10205448
TI  - Using logistic regression to describe the length of breastfeeding: a study in
      Guadalajara, Mexico.
AB  - This study seeks, through a logistic regression model, to describe the pattern of
      breastfeeding duration in Guadalajara, Mexico, during 1993. A multistage random
      sample of children under 1 year of age (n = 1036) was studied; observational data
      regarding breastfeeding duration, obtained through a "status quo" procedure, were
      compared with prevalence rates obtained from the logistic regression model.
      Modeling the duration of breastfeeding during the first year of life rather than
      only analyzing observational data helps researchers to understand this process in
      a dynamic and quantitative way. For example, uncommon indicators of breastfeeding
      were derived from the model. These indicators are impossible to obtain from
      observational data. The prevalence curve estimated through the logistic model was
      adequately fitted to observed data: there were no significant differences between
      the number or distribution of breastfed infants observed and those predicted by
      the model. Moreover, the model revealed that less than 40% of the children were
      breastfed in the fourth month of life; the median age for weaning was 39.3 days;
      55% of the potential breastfeeding in the first 4 months did not occur; and the
      greatest abandonment of breastfeeding in the first 4 months was observed in the
      first 60 days. Thus, logistic regression seems a suitable option to construct a
      population-based model that describes breastfeeding duration during the first
      year of life. The indicators derived from the model offer health care providers
      valuable information for developing programs that promote breastfeeding.

PMID- 10205449
TI  - Breastfeeding and health professional encouragement.
AB  - The objective of the study was to ascertain the nature of health professional
      contacts related to breastfeeding for 341 women. Subjects were prospectively
      queried by phone or home visit over a 20-week period regarding the number and
      nature of contacts with health care professionals related to breastfeeding.
      Lactation consultants gave significantly more positive encouragement (98%) (p =
      .01) than either nurses (75%) or physicians (68%) did. However, of the 233 health
      provider contacts that included breastfeeding advice, only 21% involved lactation
      consultants. Primiparae were likely to decrease their level of breastfeeding if a
      health professional encouraged supplemental foods (39%) or weaning (86%) during
      the prior week. Multiparae who were experienced at breastfeeding (3+ weeks
      breastfeeding the previous infant) decreased their breastfeeding slowly across
      the weeks with the current infant, and their level of breastfeeding in general
      appeared independent of health care provider advice. Multiparae who lacked
      previous sustained breastfeeding experience (0-3 weeks) had the most rapid
      decrease (65%) in their breastfeeding rates even with health care provider
      encouragement to continue. Thus, they too appeared to act independently of health
      care provider advice.

PMID- 10205452
TI  - Workplace lactation support, Part II: Working with the workplace.
AB  - Several factors, including new breastfeeding recommendations by the American
      Academy of Pediatrics, increasing numbers of women with young children in the
      workforce, more women initiating breastfeeding, and a strong economy combine to
      make this an ideal time to promote breastfeeding in the workplace. In a previous
      article, we presented a return-to-work breastfeeding assessment tool to evaluate
      lactation support in workplaces. This article focuses on the workplace itself,
      presenting a continuum of types of workplace lactation support; the key players
      in the workplace, new mothers, supervisors, and human resource managers, who are
      instrumental in supporting breastfeeding at work; workplace philosophies and
      their impact on workplace lactation support and strategies to help lactation
      consultants work with companies as their clients in establishing lactation
      support programs.

PMID- 10205451
TI  - Teaching tools for breastfeeding.

PMID- 10205454
TI  - Human milk banks in Brazil.

PMID- 10205453
TI  - Breastfeeding in the woman with a compromised nervous system.
AB  - An increasing number of women with physical limitations are choosing to conceive
      and are entering the health care system for the care of their pregnancies. These
      women are faced with the choice of how to feed the child. Although research
      specific to lactation and nervous system disorders could not be found, this paper
      reviews selected articles from the literature on three central nervous system
      disorders: spinal cord injury, multiple sclerosis, and stroke. Potential effects
      on breastfeeding are discussed.

PMID- 10205450
TI  - Breastfeeding practices of infants with Rubinstein-Taybi syndrome.
AB  - Rubinstein-Taybi Syndrome (RTS) is a rare disorder affecting 1 out of 300,000
      people, characterized by broad thumbs and toes, distinctive facial features,
      hypotonia, and developmental delays. In this study, 180 members of an RTS parent
      group completed a survey that elucidated breastfeeding practices of infants with
      RTS. Fifty-nine percent of mothers initiated breastfeeding with an average
      duration of 7.1 months. Overall, 48% of the women reported that their child had a
      good to fair suck, and 50% were fairly to very pleased with the breastfeeding
      experience. Problems reported with breastfeeding included poor weight gain (46%),
      poor nipple grasp (35%), failure to thrive (34%), and infant fatigue (33%). In
      other populations of infants with special needs, many breastfeeding problems have
      been alleviated with instruction, proper positioning, close nutritional follow
      up, and strong encouragement by the health care team. With adequate support,
      mothers and their children with RTS can successfully carry out breastfeeding.

PMID- 10205456
TI  - Recent references.

PMID- 10205455
TI  - The safety of antituberculosis medications during breastfeeding.
AB  - Most antituberculosis drugs appear to be safe for use with breastfeeding. These
      agents are excreted in breast milk at relatively small concentrations. No adverse
      effects have been reported to date. The percentages of the therapeutic dose of
      antituberculosis agents that potentially may be delivered to the nursing infants
      range from 0.05% to 28%. Currently isoniazid, rifampin, ethambutol, streptomycin
      (first-line agents), kanamycin and cycloserine (second-line agents) are the only
      agents considered by the AAP to be compatible with breastfeeding. Unfortunately,
      there are still no clear data on the safety of pyrazinamide, ethionamide, and
      capreomycin during breastfeeding. If the mother chooses to breastfeed, it may be
      prudent to examine the infant for signs and symptoms of toxicity. In infants
      requiring treatment with antituberculosis agents, it is important to use
      therapeutic doses since drug concentrations in breast milk are not adequate as
      effective therapy for treatment or prevention. However, dosing at the lower end
      of the therapeutic range should be prescribed (i.e., 10 mg/kg/day of isoniazid)
      to decrease the risk of toxicity.

PMID- 10205457
TI  - In sickness and in health: testing the vow after transplantation.

PMID- 10205458
TI  - Organ recovery from a donor with presumed viral encephalitis: a case report and
      review.
AB  - This article reviews the pathophysiology of viral encephalitis, which is
      specifically infectious to transplant recipients, and discusses the potential
      infectivity of donors who had this virus. In addition, the case report
      demonstrates one center's experience in placing organs from a donor who was
      presumed--but not confirmed--to have viral encephalitis. When a patient with
      viral encephalitis is considered for organ donation, it is recommended that a
      brain biopsy be obtained prior to organ placement to identify the suspected virus
      or confirm the absence of any viral entity.

PMID- 10205459
TI  - The effects of donor sodium levels on recipient liver graft function.
AB  - A great deal of discussion has been generated regarding the effects of donor
      hypernatremia on recipient liver graft function. Much of this discussion is
      anecdotal and focuses on the detrimental effects of hypernatremia in the organ
      donor. The treatment of donor hypernatremia often leads to changes in donor
      management protocols. A retrospective study was conducted to determine if donor
      hypernatremia measurably alters the liver graft function of recipients. Results
      indicated that donor sodium values were unrelated to any recipient parameter
      assessed. Although further studies are pending, these findings suggest that a
      moderate rather than a severe approach to the management of donor hypernatremia
      may be preferred.

PMID- 10205462
TI  - Health promotion and disease prevention in kidney transplant recipients.
AB  - Patients with end-stage renal disease have a critical need for health
      maintenance. Due to the shortage of donor organs, kidney transplant--the
      treatment of choice for end-stage renal disease--is not available to all
      individuals listed on the national waiting list. Therefore, treatment must be
      optimal to maximize graft survival and length of life in this high-risk
      population. Transplant recipients are exposed to the inherent risks of
      immunosuppression. Chronic use of pharmocologic agents to maintain graft survival
      is associated with conditions such as coronary artery disease, stroke, infection,
      and malignancy. A needs assessment revealed that many identified risks were
      modifiable through proper education and intervention. Therefore, health promotion
      and disease prevention--namely cancer screening and prevention, cardiovascular
      risk factors, and dietary guidelines--were identified as educational priorities.
      In an environment of fiscal constraint and priority setting, transplant centers
      are obligated to provide quality outcomes with cost-containment. Transplant teams
      must therefore focus on minimizing risks and preventing diseases to reduce costs
      and produce positive long-term outcomes.

PMID- 10205461
TI  - Non-heart-beating donors: a case study in procurement.
AB  - To help meet the increasing need for transplantable organs, especially kidneys,
      organ procurement organizations are recovering organs from non-heart-beating
      patients. This article outlines the successful recovery and transplantation of
      kidneys from such a donor. Consent issues and historical background are also
      discussed.

PMID- 10205460
TI  - Improving the request process to increase family consent for organ donation.
AB  - The greatest impediment to organ donation is refusal of family consent. This
      study examined the impact of 3 modifiable elements of the donation request on
      family consent rates: (1) decoupling (i.e., the family understands and accepts
      brain death before discussion of organ donation is begun); (2) the procurement
      coordinator participates in the request for consent; and (3) donation is
      requested in a quiet, private place. Data on the request process were collected
      prospectively for 707 medically suitable potential donors who had been referred
      to 3 organ procurement organizations. The average rate of consent for donation
      was 62.2%. Higher consent rates were independently associated with the 3
      characteristics studied. These components were summarized in the Request Process
      Scale. Multivariate regression analyses indicated that consent rates can be as
      high as 74% when all 3 process elements are present. Hospitals and organ
      procurement organizations should incorporate these elements into their standard
      of practice when requesting organ donation.

PMID- 10205464
TI  - Posttransplant quality of life: a decade of descriptive studies leading to
      practice interventions. Posttransplant Quality of Life Intervention Study Group.
AB  - Following 10 years of descriptive quality-of-life studies, an innovative approach
      to outpatient care has been developed to decrease adverse events, increase
      employment, and enhance social support among renal transplant recipients. These 3
      variables were found in the authors' previous studies to be predictive of
      increased quality of life following transplantation. With funding from the
      National Institute of Nursing Research, a multidisciplinary team has been
      assembled to implement the interventions identified. This article reviews the
      previous work that led to the development of the intervention study and
      demonstrates how research can guide practice.

PMID- 10205463
TI  - Conversion from Sandimmune to Neoral in organ transplant recipients.
AB  - The pharmacokinetic profiles of Sandimmune and Neoral vary considerably among
      transplant recipients. Cyclosporine exposure is far more consistent with Neoral
      than it is with Sandimmune. Because intrapatient variability of drug exposure has
      been demonstrated to be a risk factor for chronic rejection, this difference
      becomes important. Neoral also has a linear dose response and a stronger
      correlation between trough level and drug exposure. Dose linearity greatly
      facilitates accurate dose titration. Results of controlled studies in which
      kidney, liver, and heart transplant recipients were converted from Sandimmune to
      Neoral have shown that conversion on a 1:1 mg basis results in more predictable
      bioavailability and often in reductions in cyclosporine dose. Carefully monitored
      conversion has not been associated with increased side effects, and any side
      effects that do emerge can usually be managed by taking Neoral with food,
      changing the dose from every 12 hours to every 8 hours, or through dose
      reduction.

PMID- 10205465
TI  - Attitudes of black South Africans concerning organ donation.
AB  - The availability of donor organs was analyzed following the placement of a
      transplant coordinator in Ga-Rankuwa Hospital's kidney transplant program. From
      February 1, 1992, to January 6, 1994, 44 brain-dead potential donors were
      identified. In 20 of those cases, relatives could not be reached to acquire
      consent for donation of cadaveric organs. In the remaining 24 cases, an intensive
      care resident together with a transplant coordinator obtained consent for 9
      potential donors. Over the same period, 119 (80%) of living-related potential
      donors who had been approached stated that they were willing to donate a kidney.
      This outcome suggests that among blacks, altruism is a positive factor for
      acquiring consent for organ donation. Public education is required to correct
      ignorance, misconception, and cultural beliefs regarding cadaveric donation.

PMID- 10205466
TI  - Increasing the donor pool in Chile.
AB  - The purpose of this study was to evaluate organ donation in Chile following the
      creation of the "Corporacion Nacional de Fomento de Trasplantes." The corporation
      was created in 1991 as a private, nonprofit organization whose main purpose was
      to increase the number of actual donors and multiorgan procurement. The
      organization is independent of the national government and acts as a link between
      the needs of patients and society and those of the National Ministry of Health.
      Following the creation of the corporation, the number of actual donors increased
      from 32 to 98. The number of potential donors increased 3-fold. Family refusal
      for organ donation was between 28% and 53.4%. Pediatric and marginal donors
      increased from 2% to 15%. Ninety-five percent of the donors came from Santiago,
      where 33% of the population lives and most of the efforts were concentrated. The
      corporation is working to increase organ donation throughout the rest of the
      country by organizing public campaigns; promoting knowledge about transplantation
      among medical and nursing personnel at hospitals, schools, universities, and
      social gatherings; evaluating technical and financial results; and helping with
      the processes of organ procurement.

PMID- 10205467
TI  - Patterns of genetic inheritance.
AB  - Neonatal nurses need to understand the basic patterns of genetic transmission.
      This article, the first in a series, provides an overview of Mendel's laws and
      discusses five types of transmission: single gene inheritance, chromosomal
      inheritance, multifactorial inheritance, cytoplasmic inheritance, and somatic
      cell mutations.

PMID- 10205468
TI  - Primary immunodeficiency disorders in infancy.
AB  - Certain primary immunodeficiency disorders may become evident during the first
      year of life. These disorders are characterized by recurrent infections. Prompt
      diagnosis is necessary, for infants may suffer significant morbidity and
      mortality. A basic knowledge of host defense mechanisms, including the natural
      and humoral systems, is essential to the understanding of immunodeficiency
      disorders. This article discusses the clinical presentation, evaluation, and
      treatment strategies available to infants with primary immunodeficiency
      disorders. Five specific disorders are discussed in detail, and specific
      treatments are reviewed.

PMID- 10205469
TI  - The effect of a structured neonatal resuscitation program on delivery room
      practices.
AB  - PURPOSE: This study evaluated the introduction of the Neonatal Resuscitation
      Program (NRP) of the American Academy of Pediatrics and the American Heart
      Association into the delivery room of an Irish maternity hospital. DESIGN:
      Prospective, controlled observational study of 51 deliveries before and 51
      deliveries following the training of delivery room personnel in the NRP. SAMPLE:
      Participants were 33 nurse-midwives and 11 pediatric resident physicians. MAIN
      OUTCOME VARIABLE: Evaluation of postdelivery, newborn resuscitation practices.
      RESULTS: The introduction of the NRP was associated with significant improvements
      in delivery room preparation, in the evaluation and management of the newborn
      infant, and in thermal protection at birth. Although there was a trend to use
      more free-flow oxygen following the introduction of the NRP, this was not
      statistically significant. Bag and mask ventilation was also used more frequently
      following NRP training. However, there were no significant differences in the use
      of endotracheal intubation, chest compressions, and medications. Fifteen of the
      51 infants became hypothermic prior to the introduction of the NRP; none of the
      infants developed hypothermia in the post-NRP part of the study.

PMID- 10205470
TI  - The influence of equipment weights on neonatal daily weight measurements.
AB  - PURPOSE: To determine the weight of commonly used pieces of neonatal equipment
      that can affect the accuracy of daily weight measurements. DESIGN AND SAMPLE:
      Twenty-one pieces of equipment commonly attached to the neonate at the time of
      daily weight measurement were selected for analysis. Three examples of each piece
      of equipment were weighed; each one was weighed three times. All weights were
      obtained using a digital electronic diaper scale calibrated to 1 gm accuracy and
      precision. MAIN OUTCOME VARIABLE: Average weights for pieces of routine nursery
      equipment. RESULTS: Equipment weights ranged from 1 gm for an umbilical catheter
      to 23 gm for a pulse oximeter probe. There was no variation among the individual
      examples for 19 of the 21 pieces of equipment. There was a small variation in
      weight for the pulse oximeter probe and the arm board, but these variations were
      of no clinical significance.

PMID- 10205471
TI  - Suctioning smarter: answers to eight common questions about endotracheal
      suctioning in neonates.

PMID- 10205472
TI  - What to tell parents about the developmental needs of their baby at discharge.
AB  - During the transition from hospital to home and up to the first four months from
      due date, premature infants spend less time awake, and when they are awake, they
      are less alert and may be more fussy. When they sleep, they sleep for shorter
      periods of time (shorter sleep-wake cycles) and awaken to fuss before they go
      back to sleep at night.

PMID- 10205473
TI  - The economic impact of drug therapy.

PMID- 10205475
TI  - Creativity: the fuel of innovation.
AB  - Market-leveled changes occurring in the health care industry require new and
      creative models of organization, management, and service delivery. One of today's
      primary management challenges is the development of organizational cultures that
      value innovation, change, and creativity. The adoption of an ethic of
      innovativeness allows the organization to stretch the limits of individual and
      collective knowledge, skill, and ability to meet complex consumer needs.
      Creativity within organizations is influenced by management practices in
      conjunction with creativity-relevant work group skills. A common wisdom exists
      that professional nurses are creative in finding solutions for complex patient
      care needs. The expansion of this creativity within organizational systems will
      allow for the evolution of professional nursing practice, improvement in care
      delivery, and organizational performance.

PMID- 10205476
TI  - An ethics framework for organizational change.
AB  - The proliferation of managed care has introduced conflicts of interest in health
      care that can create tension in the traditional care provider-patient
      relationship. In order to address the emerging trends and potential ethical
      dilemmas presented by managed care, health systems must develop a framework for
      intentional ethical reflection. The article outlines the essential elements of a
      caring ethical framework and describes how one integrated health system created a
      framework of ethical guiding principles and an ethical organizational structure
      to facilitate integration of those principles throughout the organization.

PMID- 10205477
TI  - Inova Health System, Falls Church, Virginia.
AB  - Inova Health System found a change strategy that supported redesign of our
      patient care delivery to improve the patient experience while changing the
      culture of the organizations, ensuring system integration and reducing costs.
      Using the large group intervention of the Conference Model we involved staff and
      physicians from the entire system to create a model of care to meet the needs of
      the future. This methodology allowed us the opportunity to tap the intellectual
      capital of the organization's and build capacity among a wide range of our staff.
      The adventure is outlined in our On the Scene.

PMID- 10205478
TI  - Creative winds of change: nurses collaborating for quality outcomes.
AB  - This article describes the collaboration of two researchers and two clinicians at
      one rural medical center to develop and implement Phase I of a project that was
      part of the Quality Indicator Initiative of the American Nurses Association
      (ANA). Changes in the health care environment led the researchers to develop
      educational programs that eventually evolved into a pilot research project to
      explore the feasibility of data collection on ANA Quality Indicators.
      Collaboration between the researchers and clinicians led to outcomes that relate
      to future efforts for collecting and analyzing data on clinical outcome
      indicators.

PMID- 10205479
TI  - A culture of change or a change of culture?
AB  - As organizations find themselves having to respond to quick changes in rapid
      succession, at some point the question of whether or not the pace is too much to
      sustain comes into play. At Sarasota Memorial Hospital, early cultural assessment
      led to implementation strategies that helped to overcome some of the barriers of
      major change.

PMID- 10205480
TI  - Health care change: challenge for nurse administrators.
AB  - Nursing administrators facing reorganization understand the difficulties and
      resistance that accompany organizational change. This article discusses
      resilience, a critical character trait for successfully managing change.
      Understanding the change process can assist those charged with the challenge of
      leading organizational change to manage the journey more effectively.

PMID- 10205481
TI  - Improving performance through change: an academic medical center's experience.
AB  - In order to perform at peak efficiency and effectiveness, health care
      organizations must be change-adept. Increased scrutiny by consumers, payers, and
      regulatory agencies is but one of the drivers necessitating change. This article
      discusses methodologies for improving performance and promoting continued success
      in an academic medical center.

PMID- 10205483
TI  - Changing world, changing systems: why managed health care demands information
      technology.
AB  - In an industry in which the only constant is change, information technology is
      increasingly becoming the means by which health care organizations manage the
      constant volatility they face. This article discusses the emerging managed care
      trends that are driving the move to open systems and increased technological
      flexibility. In addition, it explains how changing models of care are fueling the
      evolution of a new breed of clinical information systems that are
      interdisciplinary, interoperable, and outcomes focused.

PMID- 10205482
TI  - Does the "C" in JCAHO stand for change?
AB  - A retrospective of joint Commission changes from its early days to the present is
      provided in this column. How the Joint Commission on the Accreditation of Health
      care Organizations evolved from the American College of Surgeons initiative to
      standardize hospital systems and equipment is discussed. Structural standards
      developed into important functions that crossed departments within an
      organization. Discussion of the current initiatives and future challenges to
      improve care to the public is included.

PMID- 10205485
TI  - Promoting domestic violence education for nurses.
AB  - Domestic violence is one of the major health problems facing families today.
      Women in rural areas often are an overlooked population at high risk for this
      problem. Domestic violence is a concern for women, who may be patients or
      healthcare workers. Teaching about domestic violence is a very sensitive issue
      because it is often difficult for the abused to admit or confront that she is
      being abused. The authors developed an effective interactive workshop to teach
      nurses how to assess and intervene with women who have experienced domestic
      violence.

PMID- 10205484
TI  - Caregiver burden: historical development.
AB  - Within the last decade there has been a multitude of research related to the
      phenomenon of caregiver burden. Although the concept is relatively new in the
      literature, the responsibility and ultimately consequences of caring for another
      family member has existed for centuries. Often this responsibility lies with the
      female members of the family, but lately more husbands, sons, close family
      members, or friends have assumed the primary caregiver role. This article reviews
      the concept of caregiver burden from a historical perspective. Research related
      to the definition of the concept and its impact on women, men, and siblings and
      the effect of ethnicity, is discussed.

PMID- 10205486
TI  - Personal knowing in cancer nursing.
AB  - Nursing practice involves the use of different types of knowledge. This article
      provides an analysis of personal knowing, one type of nursing knowledge. It uses
      an example from the cancer nursing literature that reflects the creative and
      expressive dimensions of personal knowing. The author discusses the
      social/political process used to determine the validity of this way of knowing
      and comments on the invaluable contribution that the practice of personal knowing
      and all types of nursing knowledge lend to the discipline of nursing and to the
      art and science of cancer nursing.

PMID- 10205488
TI  - A father's grief: dealing with stillbirth.
AB  - In the end each person's experience of stillbirth is unique. There is no right or
      wrong way to grieve and each person defines it uniquely (Pilkington, 1993). My
      own experiences have shown me that it is important for the father to be strong
      and to take responsibility for what needs to be done, yet acknowledge his grief.
      My wife and child were the most important people at that time, and while I needed
      to grieve, I felt I could do it only my way, and at a time when I felt I had
      completed my initial responsibilities. I do not feel guilty about being strong,
      nor do I feel guilty about being weak. I do feel bad about being too proud and
      not seeking more support from groups set up specifically to help parents. Three
      years down the track, I still miss my daughter and still think of her. I have
      another child, who can never replace Angel, and when she grows up, she, too, will
      learn about her older sister.

PMID- 10205487
TI  - Every nurse can be an author: on writing for publication.

PMID- 10205489
TI  - One practice week at a glance.

PMID- 10205490
TI  - The long predicted crisis in nurse staffing is now upon us.

PMID- 10205491
TI  - Hand it back.

PMID- 10205492
TI  - Listen to the purchasers.

PMID- 10205493
TI  - Casting light on NVQs.

PMID- 10205494
TI  - Investing in the future.

PMID- 10205495
TI  - A shared experience.

PMID- 10205496
TI  - Wales: the changing scene. Interview by Tom Keighley.

PMID- 10205497
TI  - Promoting health for older women.

PMID- 10205498
TI  - Creating new nurses.

PMID- 10205499
TI  - Partnerships: the challenge for nursing.

PMID- 10205500
TI  - The bright side of managed care.

PMID- 10205501
TI  - Microbe of the month. Streptococcus pneumoniae.

PMID- 10205502
TI  - Managing a fistula.

PMID- 10205503
TI  - Appealing for compensation.

PMID- 10205505
TI  - Keeping TB in check.

PMID- 10205504
TI  - Actionstat: traumatic amputation.

PMID- 10205506
TI  - Managing hypertension.

PMID- 10205507
TI  - Opioids and pain management: what do nurses know?

PMID- 10205508
TI  - Controlling the millennium bug.

PMID- 10205509
TI  - An expert answers questions about starting an i.v. line.

PMID- 10205510
TI  - You're being deposed? Remain calm.

PMID- 10205511
TI  - Deflecting harsh words when tempers flare.

PMID- 10205512
TI  - Amphotericin B lipid complex and respiratory distress.

PMID- 10205513
TI  - Myths & facts ... about lactose intolerance.

PMID- 10205514
TI  - The button box.

PMID- 10205515
TI  - Near breathing: nurse on a vent.

PMID- 10205516
TI  - President's message. Trauma: the patient and family in crisis.

PMID- 10205517
TI  - Physiological responses to trauma.
AB  - Stress response can be physical and psychological. Physiological responses to
      stress, such as a major trauma, stimulate the sympathetic nervous system. The
      response, although necessary to maintain life, is harmful when prolonged. Nursing
      and medical management is directed at controlling the etiology and reversing the
      side effects seen in the body organs. The physical response to stressors shall be
      explored in this article.

PMID- 10205518
TI  - Psychological response to trauma.
AB  - Severe traumatic injuries to the hands, extremities, and face can produce
      significant psychological reactions. Adjustment problems are more pronounced when
      the injuries result in disfigurement and significant loss of function. Long after
      the traumatic event, persistent fear, depression, avoidance, and body image
      changes result in substantial impairment in personal, social, and occupational
      functioning.

PMID- 10205519
TI  - Self-inflicted shotgun injuries to the face: a case report.
AB  - Shotgun injuries to the face are difficult to care for due to the often massive
      tissue and bone destruction and the complications that can accompany these
      injuries. Psychological responses from the family, significant other, and nursing
      staff in dealing with disfiguring and sometimes fatal injuries are additional
      challenges that nurses will face.

PMID- 10205520
TI  - Burn injury.
AB  - An important element in the care of burns, which affect more than 2.5 million
      Americans per year, is a multidisciplinary team approach. Nurses are important
      members of the team, which also includes physicians, physical and occupational
      therapists, psychologists, rehabilitation counselors, and nutritionists among
      others. Regular communication with the team is important for consistent quality
      care.

PMID- 10205521
TI  - Lower extremity injury: complex problems, complex answers.
AB  - Patients with traumatic injury to the lower extremities are admitted to the
      hospital with multiple interrelated problems requiring an interdisciplinary team
      approach to meet their needs. This article will explore the assessment and
      formulation of nursing diagnoses, implementation of care, and patient outcomes
      achieved. It will describe the nurse's role as the link between the patient and
      the physician and other members of the health care team. The cooperative actions
      of the different health care teams that work to achieve the desired outcomes are
      explained. A case study will be presented to illustrate these points.

PMID- 10205523
TI  - Case history: avulsion injury to the penis following power take-off injury.

PMID- 10205522
TI  - An overview of maxillofacial trauma for nurses.
AB  - A team approach is necessary in order to maximally evaluate, treat, monitor, and
      rehabilitate the patient with maxillofacial injuries. An overview of the
      complexities of the management of patients with significant maxillofacial
      injuries is presented in a manner that should assist any nurse in the assessment
      and subsequent management of such patients.

PMID- 10205524
TI  - Suture repair of soft tissue lacerations.

PMID- 10205525
TI  - When does your child need a plastic surgeon?

PMID- 10205526
TI  - Principles of splinting the hand.

PMID- 10205527
TI  - The basics of nursing research: applying principles to practice.

PMID- 10205528
TI  - When is enough, enough?

PMID- 10205533
TI  - Role-evaluation packs for specialist nurses.
AB  - Specialist nurses need to demonstrate the value of their interventions. Both
      qualitative and quantitative information is needed for a complete picture.
      Information on the role's value should be circulated as widely as possible.

PMID- 10205532
TI  - A framework to evaluate the role of nurse specialists.
AB  - All professionals should measure the impact of their skills and knowledge.
      Achieving the most appropriate and effective use of resources have become common
      concerns in the NHS. In the evolution of work roles, the need to protect the
      public must take precedence over professional aspirations.

PMID- 10205534
TI  - Infection control in moving and handling.
AB  - Hospitals are obliged to provide moving and handling equipment to protect staff
      health and prevent back disorders. The use of this equipment has opened up new
      risks to patients of cross contamination and iatrogenic infection. Hospitals need
      to address this problem in a systematic way.

PMID- 10205535
TI  - An evaluation of non-verbal handover.
AB  - Verbal handover can have a detrimental effect on nursing documentation.
      Information provided by verbal handover can be retrospective and task-orientated.
      Non-verbal handover can save time and ensure documentation is properly updated.

PMID- 10205536
TI  - Focus group interviews in health-care research.
AB  - The focus group interview allows researchers to obtain data about participants'
      feelings and opinions on a particular topic. Careful consideration must be given
      to the size of the group, the participants' backgrounds, the venue and the choice
      of moderator. It is not always appropriate to generalise the findings of focus
      group interviews on to a larger population.

PMID- 10205537
TI  - Administering intravenous antibiotics at home.
AB  - Many patients with orthopaedic infections spend weeks or months in hospital for
      administration of i.v. antibiotics. Peripherally inserted central venous
      catheters can be used to give patients their medication at home. Some patients
      can be taught to administer their own antibiotics, relieving pressure of work in
      hospitals and the community and encouraging multidisciplinary practice.

PMID- 10205538
TI  - Uses of therapeutic hypothermia.
AB  - Therapeutic hypothermia is used to preserve body function during major surgery.
      While it is a valuable therapeutic process, serious physiological harm can result
      if it is allowed to continue into the postoperative phase.

PMID- 10205539
TI  - Suturing in A + E.
AB  - A&E nurses are increasingly becoming involved in wound suturing, an area
      traditionally reserved for medical staff. To achieve optimum outcomes, nurses
      require a good understanding of wound assessment, anaesthesia and suturing
      techniques.

PMID- 10205540
TI  - The use of ECGs to record heart activity.
AB  - Most ECG recorders are single- or multi-channel. PC-based recorders are slowly
      evolving. Electrodes must be placed precisely to ensure accurate recording.

PMID- 10205541
TI  - Rheumatology. Part 3: The role of surgery.
AB  - Surgery can relieve the pain of some patients with rheumatoid arthritis. Caring
      for RA patients undergoing surgery is a multidisciplinary task. Nurses have a
      major role to play in pre-operative, peri-operative and postoperative care.

PMID- 10205542
TI  - Training for the new NHS.

PMID- 10205546
TI  - Using observation for data collection.
AB  - Observation is a term that describes several methodological techniques, and can
      be used to collect qualitative or quantitative data. Non-verbal behaviour and
      tactile skills are particularly amenable to observation. The presence of an
      observer may affect the behaviour of subjects. Data collection may be influenced
      by the observers' expectations and motives.

PMID- 10205545
TI  - Higher level practice: the consumer's perspective.
AB  - New nursing job titles mean little to the general public. Nurses with the same
      title may vary in knowledge, experience and grade. Introducing a framework for
      registration of a higher level of practice is raising a number of issues and
      concerns.

PMID- 10205547
TI  - Understanding patients' health beliefs.
AB  - Health and ill-health are subject to wide interpretation between and within lay
      and professional groups. A simple relationship between health beliefs and
      behaviour cannot be assumed. Understanding an individual's health locus of
      control may help to determine the most appropriate health message for that
      person.

PMID- 10205548
TI  - TUR syndrome: a risk after prostatic surgery.
AB  - TUR syndrome occurs in approximately 7% of men following prostatic surgery. Its
      symptoms can be mistaken for the effects of anaesthesia or age. Patients require
      careful postoperative monitoring as the syndrome is treatable but can be fatal.

PMID- 10205549
TI  - Larval therapy in wound debridement.
AB  - The use of larvae (maggots) in wound management was popular in the 1930s. Now the
      advent of multi-resistant strains of bacteria has led to its reintroduction in
      some hospitals, when other avenues have been exhausted.

PMID- 10205550
TI  - Bladder retraining.
AB  - Bladder retraining is a behavioural therapy which offers many women with
      continence problems a return to normal or near normal voiding patterns. However,
      full commitment is required from patients and nurses for it to be successful.

PMID- 10205551
TI  - Maintaining patients' personal hygiene.
AB  - Maintaining patients' personal hygiene is a fundamental aspect of nursing care. A
      range of benefits can be gained when experienced nurses bathe or wash patients.
      Responsibility for patient hygiene should not be delegated to unqualified or
      inexperienced staff.

PMID- 10205552
TI  - Pulse oximeters for the detection of hypoxaemia.
AB  - The main purpose of pulse oximetry is to alert health-care professionals to the
      early stages of hypoxaemia. Pulse oximetry is an accurate and widely used method
      of monitoring peripheral saturation. As with any monitoring device, care must be
      taken to monitor the patient's vital signs. Pulse oximetry measures the
      saturation of arterial haemoglobin, not the adequacy of ventilation.

PMID- 10205553
TI  - Rheumatology. Part 2: The role of medication.
AB  - Rheumatoid arthritis is a chronic, long-term inflammatory disease. Symptom relief
      can be achieved with analgesia and NSAIDs. The only way to influence its progress
      is by administering disease-modifying anti-rheumatic drugs.

PMID- 10205555
TI  - Burn tragedy.

PMID- 10205554
TI  - Important changes in home health care.

PMID- 10205556
TI  - Nurses' assessment of patients' cognitive orientation in a rehabilitation
      setting.
AB  - Orientation is a critical determinant of a patient's neurological status and an
      indicator of change in condition during hospitalization. The ways rehabilitation
      nurses assess orientation and the manner in which findings are interpreted and
      reported can have significant implications for the care of neurologically
      compromised patients. This study used a questionnaire to examine how 52 nurses
      appraised and reported the results of orientation evaluations. Analyses produced
      descriptive statistics and correlational measures for determining nurses'
      tendencies and consistency in evaluating orientation. Most respondents,
      regardless of their education and experience, used a clinical interview, rather
      than psychometric tests, as a basis for forming opinions about orientation.
      Although most evaluations included assessments in terms of person, time, place,
      and circumstance, no consistent pattern emerged regarding questioning or in the
      ways results were reported. Findings revealed a significant lack of consensus in
      terms of assessing and reporting orientation results, which could reflect
      insufficient awareness about the importance of maintaining consistency in
      evaluations, the relevance of using standardized evaluations and comparing
      measures over time, and the necessity of agreeing on how to report cognitive
      disturbances.

PMID- 10205557
TI  - A patient education MAP: an integrated, collaborative approach for
      rehabilitation.
AB  - Because Roosevelt Warm Springs Institute for Rehabilitation has been faced with
      decreasing patient lengths of stay, increasing patient acuity, and changes in the
      nurse staffing mix, nurses wanted to ensure that patients and their families were
      receiving appropriate education and learning the skills required to provide safe
      and competent self-care in the home. As a result, they developed a patient
      education action plan. This multidiscipline action plan (MAP) involved changing
      from a multidisciplinary to an interdisciplinary approach toward patient and
      family education. This plan provides a framework that is linked to expected
      outcomes for education during a patient's stay, reduces the redundancy of patient
      education by professionals from different disciplines, and increases
      collaboration. Teaching modules that outline and provide all of the information
      an educator needs to effectively teach a patient or group of patients make up the
      basis for the MAP system. This article describes the MAP system and the related
      continuous quality improvement activities, offers documentation forms, and
      identifies a structural path.

PMID- 10205558
TI  - Autonomic dysreflexia: a clinical rehabilitation problem.
AB  - Autonomic dysreflexia, or hyperreflexia, is a life-threatening condition that can
      occur in a person with a spinal cord injury at or above the T6 level. The classic
      signs and symptoms are severe hypertension, pounding headache, and diaphoresis.
      Prevention is the key to avoiding this disease process. This article reviews the
      pathophysiology, precipitating factors, signs and symptoms, nursing management,
      and effects of the problem. All healthcare providers must be aware of this
      condition in order to prevent permanent impairments in clients who may experience
      it.

PMID- 10205559
TI  - Sexual dysfunction in men on chronic hemodialysis: a rehabilitation nursing
      concern.
AB  - The rehabilitation potential of hemodialysis patients is hampered by the many
      complications associated with a uremic state and hemodialysis therapy. One
      complication that is particularly disturbing to male hemodialysis patients is
      sexual dysfunction, which affects about 50% of them and whose exact cause is
      unknown. This article reviews the literature regarding factors associated with
      sexual dysfunction in male patients on dialysis and the implications for
      rehabilitation nursing practice.

PMID- 10205561
TI  - Searching the Web.

PMID- 10205560
TI  - The diagnosis of multiple sclerosis: Peplau's Interpersonal Relations Model in
      practice.
AB  - Multiple sclerosis (MS) is a chronic, frequently progressive neurological disease
      of unknown etiology and uncertain trajectory. Physicians and nurses have
      historically been uncomfortable broaching the topic of a possible MS diagnosis
      with patients and have tended instead to talk about it in euphemistic terms.
      However, with the development of therapeutic agents that may be more effective
      early in the disease course, the early communication of diagnostic and treatment
      information has become increasingly important. In our MS clinic, individual with
      MS symptoms are rapidly referred and assessed by a team of experienced physicians
      and nurses. Our experience with this referral process has led to our adoption of
      Peplau's Interpersonal Relations Model as a guide to nursing practice. The
      central element of Peplau's model is the development of a therapeutic
      relationship between patient and nurse. This relationship develops through four
      overlapping stages: orientation, identification, exploitation, and resolution.
      The collaborative relationship that develops between nurse and patient enhances
      problem solving and creates a strong bond that is essential across the long
      trajectory of the illness.

PMID- 10205562
TI  - Ethics in action. A 23-year-old accident victim with acute brain injury refuses
      treatment.

PMID- 10205563
TI  - The patient with Crohn's disease.

PMID- 10205564
TI  - When MRSA reaches into long-term care.

PMID- 10205566
TI  - Getting UTI patients back on track.

PMID- 10205565
TI  - Ethics on the job: a survey. Where nurses stand on abortion.

PMID- 10205567
TI  - Life care planning.

PMID- 10205568
TI  - Accidental needlesticks.

PMID- 10205569
TI  - Safeguarding newborns: managing the risk.

PMID- 10205570
TI  - New warning issued on OTC analgesics.

PMID- 10205571
TI  - Ethics in action. Nursing assistants are jeopardizing your patients' welfare.

PMID- 10205572
TI  - CHF education saved this hospital $173,000.

PMID- 10205573
TI  - Don't let patient falls trip you up.

PMID- 10205574
TI  - Rapid change starts small, goes big.

PMID- 10205575
TI  - Bombs and other blasts.

PMID- 10205576
TI  - Consider this career path.

PMID- 10205577
TI  - A new option for burn victims.

PMID- 10205578
TI  - Women & heart disease.

PMID- 10205579
TI  - Ethics on the job: a survey. When is it time to die?

PMID- 10205580
TI  - When patient care gets too personal.

PMID- 10205581
TI  - Managing chronic cancer pain.

PMID- 10205582
TI  - Volunteerism: just say yes.

PMID- 10205583
TI  - Asthma and leukotrienes: antileukotrienes as novel anti-asthmatic drugs.
AB  - Antileukotriene drugs inhibit the formation or action of leukotrienes, which are
      potent lipid mediators generated from arachidonic acid in lung tissue and
      inflammatory cells. The leukotrienes were discovered in basic studies of
      arachidonic acid metabolism in leucocytes 20 years ago and were found to display
      a number of biological activities which may contribute to airway obstruction.
      Clinical studies with antileukotriene drugs have indeed demonstrated that
      leukotrienes are significant mediators of airway obstruction evoked by many
      common trigger factors in asthma. Moreover, treatment trials have established
      that this new class of drugs has beneficial anti-asthmatic properties, and
      several antileukotrienes have recently been introduced as new therapy of asthma.
      This communication presents an overview of the biosynthesis of leukotrienes,
      their biological effects and clinical effects of antileukotrienes in the
      treatment of asthama.

PMID- 10205585
TI  - Musculo-skeletal pathology in patients with angina pectoris and normal coronary
      angiograms.
AB  - PURPOSE: To evaluate the role of the musculo-skeletal apparatus in patients with
      angina pectoris despite normal coronary angiograms. DESIGN: A survey of patients
      and controls investigated by blinded observers. SETTING: A tertiary cardiologic
      referral centre. SUBJECTS: Thirty women and 18 men (mean age 52.9 years) with
      chest pain of an average duration of 3 years and 11 months were investigated. All
      had normal resting electrocardiograms. No patients showed evidence of left
      ventricular hypertrophy or valvular heart disease on echocardiography and all had
      a normal coronary angiogram. All had left ventricular ejection fraction > 50%,
      and none had signs of coronary vasospasm. Eighteen healthy persons (10 women and
      eight men, mean age 51.2 years) served as controls. MAIN OUTCOME MEASURES: The
      group frequency of chest wall complaints, spinal radiograph and physical
      examination findings; pressure pain thresholds. RESULTS: The patients had
      significantly more complaints of pain from the neck, chest, and thoracic spine,
      and sensations and pain radiating to the arms than the controls. The patients had
      more degenerative findings on radiograph than the controls, mainly at levels C4
      C7. Physical examination showed that abnormal findings were significantly more
      frequent in patients than in the control group in the anterior and posterior
      chest wall, in the spine at levels Th1-Th6 and in the muscles of the neck and
      shoulder girdle. There were no statistically significant differences in pain
      thresholds or in neurological examination. CONCLUSION: The musculo-skeletal
      abnormalities observed in the patients could include reflex mechanisms. Whether
      the abnormal findings are mainly responsible for the angina pectoris symptoms or
      merely epiphenomena warrants further study.

PMID- 10205584
TI  - Bedtime uncooked cornstarch supplement prevents nocturnal hypoglycaemia in
      intensively treated type 1 diabetes subjects.
AB  - OBJECTIVES: The present study tests two interrelated hypotheses: (1) that bedtime
      ingestion of uncooked cornstarch exerts a lower and delayed nocturnal blood
      glucose peak compared with a conventional snack; (2) that bedtime carbohydrate
      supplement, administered as uncooked cornstarch, prevents nocturnal hypoglycaemia
      without altering metabolic control in intensively treated type 1 diabetes (IDDM)
      patients. DESIGN AND SUBJECTS: The above hypotheses were tested separately (1) by
      pooling and analysing data from two overnight studies of comparable groups of
      patients with non-insulin dependent diabetes mellitus (NIDDM) (14 and 10
      patients, respectively), and (2) by a double-blind, randomized 4-week cross-over
      study in 12 intensively treated IDDM patients. SETTING: Sahlgrenska University
      Hospital, Goteborg. Sweden. INTERVENTIONS: (1) Ingestion of uncooked cornstarch
      and wholemeal bread (0.6 g of carbohydrates kg-1 body weight) and carbohydrate
      free placebo at 22.00 h. (2) Intake of uncooked cornstarch (0.3 g kg-1 body
      weight) and carbohydrate-free placebo at 23.00 h. MAIN OUTCOME MEASURES: (1)
      Nocturnal glucose and insulin levels; (2) frequency of self-estimated
      hypoglycaemia (blood glucose [BG] levels < 3.0 mmol L-1) at 03.00 h, HbA1c and
      fasting lipids. RESULTS: Bedtime uncooked cornstarch ingestion led to a lower
      (2.9 +/- 0.5 vs. 5.2 +/- 0.6 mM, P = 0.01) and delayed (4.3 +/- 0.6 vs. 2.0 +/-
      0.0 h, P < 0.01) BG peak, compared with a conventional snack, in NIDDM patients.
      Four weeks of bedtime uncooked cornstarch supplement, as compared with placebo,
      led to a 70% reduction in the frequency of self-estimated hypoglycaemia at 03.00
      h (P < 0.05), without affecting HbA1c or fasting lipids in IDDM patients.
      CONCLUSIONS: Uncooked cornstarch, ingested at bedtime, mimicked the nocturnal
      glucose utilization profile following insulin replacement, with a peak in blood
      glucose after 4 h. In IDDM patients, bedtime uncooked cornstarch supplement
      diminished the number of self-estimated hypoglycaemic episodes, without adversely
      affecting HbA1c and lipid levels. Hence, bedtime uncooked cornstarch ingestion
      may be feasible to prevent a mid-nocturnal glycaemic decline following insulin
      replacement in IDDM and, based on the nocturnal blood glucose profile, may also
      be preferable compared with conventional snacks.

PMID- 10205586
TI  - Studies in hypertriglyceridaemia. VI: Serum lathosterol concentration is raised
      in hypertriglyceridaemic non-diabetic males with hyperinsulinaemia.
AB  - OBJECTIVES: To assess the cholesterol synthesis rate in primary
      hypertriglyceridaemia using the serum unesterified lathosterol concentration as
      an indicator. DESIGN: A cross-sectional, case-control study. SETTING: The
      Karolinska Hospital, Stockholm. SUBJECTS: Randomly selected hyper- (n = 53) and
      normotriglyceridaemic (n = 57) males, 40-50 years, with a fasting serum
      triglyceride concentration (mean +/- SD) of 3.81 +/- 1.65 and 1.28 +/- 0.53 mmol
      L-1, respectively. The exclusion criterion was diabetes mellitus, defined
      according to the World Health Organization (WHO) guidelines. MAIN OUTCOME
      MEASURES: To compare the fasting serum concentration distributions of
      lathosterol, a cholesterol precursor, in hyper- and normotriglyceridaemic groups.
      RESULTS: Thirty-six per cent of the hypertriglycerdaemic group had raised serum
      lathosterol concentrations, based on the 90th percentile of the lathosterol
      distribution of the normotriglyceridaemic group. In the hyper- but not in the
      normotriglyceridaemic group, lathosterol concentration was directly correlated
      with serum insulin responses to oral (r = 0.38; P = 0.007) and intravenous (r =
      0.41; P = 0.005) glucose challenges. CONCLUSIONS: One-third of a randomly
      selected non-diabetic hypertriglyceridaemic population had an increased serum
      lathosterol concentration and this might indicate an increased cholesterol
      synthesis rate compatible with increased production of VLDL particles, possibly
      as the result of chronic hyperinsulinaemia.

PMID- 10205587
TI  - The different effects of a Gln27Glu beta 2-adrenoceptor gene polymorphism on
      obesity in males and in females.
AB  - OBJECTIVES: To investigate the role of a polymorphism in codon 27 (Gln27Glu) of
      the beta 2-adrenoceptor gene for obesity in males compared to previously
      investigated females with an association of this polymorphism to obesity. DESIGN:
      Population-based study. SETTING: Medical department at a University Hospital.
      SUBJECTS: A total of 138 non-related Swedish males with body mass indexes (BMI)
      in the range 19.4-53.4 kg m-2 were recruited as: healthy volunteers, healthy
      obese subjects and subjects undergoing surgery for uncomplicated gallstone or
      abdominal hernia. In order to investigate the impact of gender, the results were
      compared with a subset of an earlier investigated female population of 109
      Swedish females. Obesity was defined as a BMI > 27 kg m-2. MAIN OUTCOME MEASURES:
      Genotype examination of beta 2-adrenoceptor polymorphism in codon 27 with
      polymerase chain reaction and restriction fragment length polymorphism. RESULTS:
      The allele frequency of Gln27 and Glu27 did not differ between males and females
      when obese and non-obese subjects were investigated together. However, in obese
      males, the frequency of the Glu27 allele was significantly decreased (P = 0.034),
      whereas the frequency of this allele was increased in obese females (P = 0.013).
      No impact of the female androgen status on the distribution of the Gln27Glu
      polymorphism could be demonstrated in the obese females. CONCLUSION: A positive
      association between obesity and the Glu27 genetic variant in the beta 2
      adrenoceptor exists in females, whereas in males there is a negative correlation
      between Glu27 and obesity. The findings suggest that different genetic factors
      contribute to obesity in males and females.

PMID- 10205588
TI  - Post-streptococcal reactive arthritis: a clinical and serological description,
      revealing its distinction from acute rheumatic fever.
AB  - OBJECTIVE: To follow-up prospectively patients with arthritis after infection
      with beta-haemolytic streptococci of Lancefield group A (beta HSA), with emphasis
      on clinical characteristics and serological features. We additionally
      investigated whether these patients, though often fulfilling the Jones' criteria
      for acute rheumatic fever (ARF), had a disease with clinical characteristics
      different from ARF. DESIGN: We performed a systematic prospective observational
      study of consecutive patients at a Dutch Outpatient Clinic and Department of
      Rheumatology, with arthritis after throat infection with beta HSA presenting to
      rheumatologist or internist from September 1992 until September 1996. Main
      outcome measures were clinical and biochemical characteristics with special
      reference to carditis. RESULTS: A total of 23 patients (21 Dutch, two Turkish;
      female/male ratio 15/8; mean (SD) age 42 (14) years) with predominantly non
      migratory arthritis were included. A positive throat swab culture was obtained in
      17%. All patients showed a significant rise of antistreptolysine-O (ASO; normal <
      200 i.u. mL-1) and antideoxyribonuclease-B (anti-DNase-B; normal < 200 i.u. mL-1)
      titre. The mean (SEM) maximal ASO was 1305 (195) i.u. mL-1, and anti-DNase-B
      titre 980 (115) i.u. mL-1. Arthritis was present in mean (SEM) 5.4 (0.9) joints:
      2.2 (0.7) small, 3.2 (0.4) larger joints. The arthritis was monarticular in 23%
      of the patients, oligoarticular in 35%, and polyarticular in 43%. Skin
      abnormalities were present in 12 patients: erythema nodosum in seven patients
      (30%), and erythema multiforme in five patients (22%). A transient cholestatic
      hepatitis was found in four patients (17%). In two patients a transient first
      degree conduction block was found; however, neither echocardiography nor clinical
      course supported carditis. All patients were advised to receive monthly
      penicillin prophylaxis during a period of 2 years. Two patients refused to follow
      medical advice: in one a non-migratory arthritis recurred 15 months after the
      first episode of arthritis. CONCLUSION: Commonly, arthritis secondary to beta HSA
      infection in the Netherlands, a prosperous West-European country with State
      Welfare, is not accompanied by carditis, contrary to literature on classical ARF.
      Other factors discriminating it from ARF are the age of onset, the non-migratory
      character of the arthritis, the high frequency of erythema nodosum and
      multiforme, as well as the presence of transient hepatitis. As arthritis is the
      hallmark of this syndrome, post-streptococcal reactive arthritis (PSRA) is the
      most proper name for this disease entity. Whether penicillin profylaxis is needed
      in PSRA, as it is in ARF, warrants further prospective investigation.

PMID- 10205589
TI  - Cross-sectionally assessed carotid intima-media thickness relates to long-term
      risk of stroke, coronary heart disease and death as estimated by available risk
      functions.
AB  - OBJECTIVE: To relate cross-sectionally assessed indicators of carotid
      atherosclerosis measured in participants of the Rotterdam Study to absolute 10-12
      year risks of stroke, coronary heart disease and death estimated by risk
      functions available from other studies. SETTING: General population living in the
      suburb of Ommoord in Rotterdam, The Netherlands. SUBJECTS: A sample of men and
      women (n = 1683), aged 55 years or over, drawn from participants from the
      Rotterdam Study (n = 7983). MAIN OUTCOMES MEASURES: Three risk scores were used
      to estimate for each individual the absolute risk of stroke, coronary heart
      disease and death within 10-12 years as a function of their cardiovascular risk
      factor profile. Cross-sectionally measured indicators of carotid atherosclerosis
      (presence of atherosclerotic lesions and common carotid intima-media thickness)
      were subsequently related to these risk scores. RESULTS: The 10-year absolute
      risk of stroke increased linearly from 4.8% (95% CI = 3.8, 5.8) for subjects in
      the lowest quintile to 16.1% (12.3, 21.9) for subjects in the highest quintile of
      common carotid intima-media thickness distribution. Similarly, the 10-year
      absolute risk for coronary heart disease rose from 13.1% (95% CI = 12.0, 14.2) to
      23.4% (95% CI = 21.4, 25.4), whereas the risk of death within 11.5 years rose
      from 15.0% (95% CI = 12.8, 17.4) in the lowest quintile to 46.0% (42.8, 49.3) in
      the upper quintile. The absolute risks of stroke, coronary heart disease or death
      rose from 8.8, 15.8 and 26.9% to 14.3, 19.8 and 40.9%, respectively, when plaques
      in the common carotid artery were present. Similar findings were observed for
      plaques in the carotid bifurcation. CONCLUSION: Common carotid intima-media
      thickness and carotid plaques are markers for increased risk of stroke, coronary
      heart disease and death within 10-12 years.

PMID- 10205590
TI  - Autoimmunity and extranodal lymphocytic infiltrates in lymphoproliferative
      disorders.
AB  - OBJECTIVE: To examine the relationship between autoimmunity and extranodal
      lymphocytic infiltrates in different lymphoproliferative disorders with
      immunoglobulin alterations. SUBJECTS AND DESIGN: A clinical review combined with
      a retrospective cohort study of 380 patients, 28 with monoclonal gammopathy of
      undetermined significance, three with common variable immunodeficiency, 147 with
      chronic lymphocytic leukaemia, 57 with Waldenstrom's macroglobulinaemia and 145
      with non-Hodgkin's malignant lymphoma. SETTING: A university hospital and The
      State Serum Institute in Copenhagen. INTERVENTION: Clinical examination of each
      patient with special attention to chronic inflammatory and autoimmune
      manifestations. Biopsies were taken from non-infectious infiltrates, some of
      which were additionally tested with PCR analysis for gene rearrangements.
      Serological screening with a test battery for various autoantibodies was used in
      combination with techniques for the detection of M-components and monoclonal B
      cell proliferation. MAIN OUTCOME MEASURES: Clinical and/or serological autoimmune
      manifestations, M-component and other immunoglobulin alterations, and
      inflammatory tissue changes were studied in patients with chronic inflammatory,
      polyclonal or oligoclonal pseudolymphomas and in monoclonal, malignant extranodal
      lymphomas. RESULTS: In 380 consecutive patients, 49 (12.9%) had extranodal
      manifestations, of whom 47 also had autoimmune manifestations. Nearly half of the
      47 patients had more than one autoimmune manifestation. There was a strong
      correlation between clinical signs and corresponding autoantibodies such as anti
      SSA and -SSB antibodies in Sjogren's syndrome (10 cases), antithyroid peroxidase
      antibodies in thyroiditis and Graves' disease (10 cases), and parietal cell
      antibodies in gastric ulcers with maltoma (12 cases). Clinical and serological
      signs of autoimmunity correlated strongly with female sex (34, 72% women; and 13,
      28% men) and with immunoglobulin alterations. CONCLUSIONS: To our knowledge this
      is the first systematic review of B-lymphoproliferative and autoimmune disorders
      indicating that pseudolymphoma and malignant lymphomas, including maltomas, may
      develop in the context of a permanent autoantigenic drive.

PMID- 10205591
TI  - Parasympathetic function during deep breathing in the general population:
      relation to coronary risk factors and normal range.
AB  - OBJECTIVES: To examine the association between the parasympathetic function
      assessed by deep breathing-induced heart rate variability (HRV) and coronary risk
      factors and to establish a reference range for deep breathing-induced HRV.
      DESIGN: Cross-sectional population-based study. SETTING: The municipality of
      Horsens, Denmark. SUBJECTS: One hundred and ninety-four individuals aged 40-67
      years without diabetes, atrial fibrillation or a pacemaker randomly selected from
      the population. MAIN OUTCOME MEASURES: During deep breathing at 6 respiratory
      cycles min-1, an ECG was taken and in three consecutive cycles the longest R-R
      interval during expiration (E) and the shortest during inspiration (I) were
      selected. The mean ratio (E/Iratio) and the mean difference in instantaneous
      heart rate (E/Idiff) were taken as expressions of the parasympathetic function.
      RESULTS: In multivariate analysis, E/Idiff was reduced with increasing age (P <
      0.0005) and left ventricular mass (P = 0.008), with ECG sign of probable previous
      myocardial infarction (P = 0.020) and the use of cardiac medication (P = 0.018)
      and positively correlated to heart rate (P = 0.030). The E/Iratio was diminished
      with increasing age (P = 0.001), left ventricular mass (P = 0.003), waist-hip
      ratio (P = 0.044), with ECG sign of probable previous myocardial infarction (P =
      0.012) and use of cardiac medication (P = 0.020), but no association was found
      with heart rate (P = 0.92). In both E/Idiff and E/Iratio, no correlation was
      found to lipids, blood pressure or alcohol consumption. In the group not on
      cardiac medication, without left ventricular hypertrophy or ECG sign of probable
      myocardial infarction, E/Idiff and E/Iratio were still independently correlated
      to age and left ventricular mass. In this group, equations defining the age
      corrected 5th percentile were calculated. CONCLUSIONS: The parasympathetic
      function as assessed by deep breathing-induced HRV in the general population is
      reduced in older people, and in individuals on cardiac medication, with left
      ventricular hypertrophy or ECG signs of myocardial infarction. Even in healthy
      persons the parasympathetic function is inversely associated with age and left
      ventricular mass. Values of E/Idiff above (4.39-0.033 x age)2 and readings of
      E/Iratio above 1 + exp (-1.12-0.0198 x age) can be regarded as normal.

PMID- 10205592
TI  - Aetiology and clinical significance of thrombocytosis: analysis of 732 patients
      with an elevated platelet count.
AB  - OBJECTIVE: To determine the aetiology and clinical significance of an elevated
      platelet count (thrombocytosis) in a large cohort of patients. DESIGN: A
      retrospective review of the medical records was performed on all patients, who
      had at least one platelet count > or = 500 x 10(9) L-1. SETTING: Departments of
      Medicine and Surgery, University of Ulm, Germany. SUBJECTS: A total of 732
      patients with thrombocytosis. MAIN OUTCOME MEASURES: Classification of
      thrombocytosis and thromboembolic complications, and evaluation of laboratory
      parameters distinguishing between primary and secondary thrombocytosis. RESULTS:
      Of the total of 732 patients, 89 (12.3%) had primary and 643 (87.7%) had
      secondary thrombocytosis. Essential thrombocythaemia was observed in 40 of 89
      patients (45%) with primary thrombocytosis. The most frequent causes of secondary
      thrombocytosis were tissue damage (42%), infection (24%), malignancy (13%) and
      chronic inflammation (10%). Primary thrombocytosis was significantly associated
      with a higher platelet count and an increased incidence of both arterial and
      venous thromboembolic complications. In secondary thrombocytosis, thromboembolic
      events were restricted to the venous system and occurred only in the presence of
      other risk factors. Mean values of leucocyte count, haematocrit, erythrocyte
      sedimentation rate, fibrinogen, serum potassium and lactate dehydrogenase were
      significantly different in primary and secondary thrombocytosis. CONCLUSIONS: The
      finding of an elevated platelet count on routine blood examination has
      diagnostic, prognostic and therapeutic implications. It is of clinical importance
      to distinguish between primary and secondary thrombocytosis, as thrombotic
      complications occur more frequently in primary thrombocytosis. Unless additional
      risk factors are present, secondary thrombocytosis is not associated with a
      significant risk for thromboembolic events.

PMID- 10205593
TI  - Cutaneous necrosis as a terminal paraneoplastic thromboembolic event in a patient
      with non-Hodgkin's lymphoma.
AB  - Thrombotic complications in non-Hodgkin's lymphoma often originate in the large
      veins. We describe a patient with refractory advanced high-grade lymphoma who
      presented with the rare complication of extensive cutaneous necrosis due to
      thrombosis of dermal vessels; there was also a recent new peak of monoclonal IgM
      kappa protein. Direct immunofluorescence demonstrated immune deposits with
      complement in the dermal vessel wall. Based on these observations and on
      published data, we suggest that these complexes were the trigger for the
      thrombotic events and that the monoclonal IgM acted as xenoreactive antibodies,
      initiating a cascade of events. The first step of this cascade was activation of
      the complement and the membrane attack complex, which caused secretion of IL-1
      alpha by endothelial cells, followed by overexpression of tissue factor on the
      surface of the dermal vessel wall endothelium. Dermal vessel thrombosis was the
      final event in this cascade.

PMID- 10205594
TI  - Life-threatening ventricular tachycardia due to liquorice-induced hypokalaemia.
AB  - We report on a patient with hypokalaemia and severe ventricular tachycardia of
      torsades de pointes type which turned out to be caused by an apparent
      mineralocorticoid excess syndrome associated with liquorice consumption. The
      patient, a 44-year-old woman, attended the hospital because of irregular heart
      rhythm and she displayed repeated episodes of life-threatening torsades de
      pointes ventricular tachycardia. The initial serum potassium was low: 2.3 mmol L
      1. The patient was treated with potassium and magnesium infusions, and the
      dysrhythmias eventually ceased. Endocrinological investigations showed no
      indication of Cushing's syndrome or hyperaldosteronism. After some time it became
      clear that the patient had ingested moderately large amounts of liquorice every
      day for 4 months. After the patient stopped this habit the hypokalaemia and
      dysrhythmias did not recur and after more than 1 year there are no signs of
      cardiac illness.

PMID- 10205595
TI  - Use and misuse of atherosclerosis.

PMID- 10205596
TI  - Metabolic abnormalities related to cardiovascular risk in primary
      hyperparathyroidism: effects of surgical treatment.

PMID- 10205597
TI  - Lyme disease vaccine.

PMID- 10205598
TI  - Modafinil for narcolepsy.

PMID- 10205599
TI  - Qualitative determination of polyvinylpyrrolidone type by near-infrared
      spectrometry.
AB  - Soluble polyvinylpyrrolidones are very useful and versatile pharmaceutical
      auxiliaries. The different types of povidone are characterised by their viscosity
      measured in water, expressed as a K-value. We have developed a rapid, accurate,
      reliable, and non-destructive near infrared (NIR) spectroscopy method for the
      determination of PVP type and consequently identification thereof. We have
      implemented chemometrics onto NIR spectra collected in diffuse reflectance mode
      using fibre optics to build a qualitative model that enables us to obtain useful
      analytical information. A principal component analysis and a modelling technique
      soft independent modelling of class analogy (SIMCA) were applied. An approach to
      validate the method was developed.

PMID- 10205600
TI  - Permeation of several drugs through keratinized epithelial-free membrane of
      hamster cheek pouch.
AB  - The hamster cheek pouch mucosa was selected as a substitute for the human buccal
      mucosa in an in vitro permeation study. Considering that a keratinized layer is
      not present in the human buccal mucosa, keratinized epithelial-free hamster cheek
      pouch (KEF-membrane) was prepared by chemical splitting. To confirm the
      usefulness of the KEF-membrane, a permeation study was conducted using several
      drugs with different lipophilicities. The permeability coefficient of hydrophilic
      drugs through the KEF-membrane (Pkef) was significantly greater than that through
      a viable KEF-membrane (Pkef-viable), which was estimated by using the
      permeability coefficient of the viable full-thickness membrane and that of the
      keratinized layer. On the other hand, the Pkef values of lipophilic drugs were
      comparable with the Pkef-viable values. Furthermore, the ratio of these P values
      (Pkef/Pkef-viable) decreased with increasing lipophilicity of drugs. These
      findings indicate that the KEF-membrane may be useful for buccal permeation
      studies of lipophilic drugs.

PMID- 10205601
TI  - Non-traditional plasticization of polymeric films.
AB  - The objective of this study was to investigate the influence of methylparaben,
      ibuprofen, chlorpheniramine maleate and theophylline on the thermal and
      mechanical properties of polymeric films of Eudragit RS 30 D. The effects of
      methylparaben and ibuprofen in the film coating on the rate of drug release from
      Eudragit RS 30 D coated beads were also studied. The physical and mechanical
      properties of the cast films and coated beads were investigated using thermal
      analysis, tensile testing, X-ray diffraction analysis and dissolution testing.
      The results demonstrated that the glass transition temperature of the Eudragit RS
      30 D decreased with increasing levels of methylparaben, ibuprofen and
      chlorpheniramine maleate in the film. Theophylline exerted no influence on the
      thermal properties of the polymer. The higher levels of the ibuprofen and
      methylparaben incorporated into the film resulted in a decrease in the tensile
      strength of the film. The decrease in Young's modulus of Eudragit RS 30 D coated
      beads was attributed to an increase in the flexibility of the polymeric films
      when the level of methylparaben or ibuprofen in the polymeric dispersion was
      increased. The dissolution data demonstrated that the rate of release of the
      ibuprofen from coated beads was decreased by increasing the amount of ibuprofen
      and methylparaben in the polymeric film coating.

PMID- 10205602
TI  - The effects of disordered structure on the solubility and dissolution rates of
      some hydrophilic, sparingly soluble drugs.
AB  - The effects of experimental design on the apparent solubility of two sparingly
      soluble hydrophilic compounds (barium sulphate and calcium carbonate) were
      studied in this paper. The apparent solubility appeared to be primarily dependent
      on the amount of solute added to the solvent in each experiment, increasing with
      increased amounts. This effect seems to be due to the existence of a peripheral
      disordered layer. However physico-chemical methods used in the present study were
      not able to unambiguously verify the existence of any disorder in the solid state
      structure of the drugs. At higher proportions of solute to solvent, the
      solubility reached a plateau corresponding to the solubility of the disordered or
      amorphous molecular form of the material. Milling the powders caused the plateau
      to be reached at lower proportions of solute to solvent, since this further
      disordered the surface of the drug particles. It was also found that the apparent
      solubility of the drugs tested decreased after storage at high relative
      humidities. A model for describing the effects of a disordered surface layer of
      varying thickness and continuity on the solubility of a substance is presented.
      This model may be used as a method for detection of minute amount of disorder,
      where no other technique is capable of detecting the disordered structure. It is
      suggested that recrystallisation of the material occurs via slow solid-state
      transition at the surface of the drug particle; this would slowly reduce the
      apparent solubility of the substance at the plateau level to the
      thermodynamically stable value. A biphasic dissolution rate profile was obtained.
      The solubility of the disordered surface of the particles appeared to be the rate
      determining factor during the initial dissolution phase, while the solubility of
      the crystalline core was the rate-determining factor during the final slower
      phase.

PMID- 10205603
TI  - Compatibility and stability of ternary admixtures of morphine with haloperidol or
      midazolam and dexamethasone or methylprednisolone.
AB  - The concentration range over which compatible admixtures of morphine
      hydrochloride with haloperidol lactate (Haldol) or midazolam hydrochloride
      (Dormicum) and dexamethasone-21-sodium phosphate (Decadron and Decadron Pack) or
      methylprednisolone-21-sodium succinate (Solu-Medrol) can be prepared was
      determined by visual evaluation of the solutions at 22 degrees C. The
      compatibility was evaluated for admixtures prepared in a ratio morphine
      hydrochloride (D1)/drug 2 (D2)/drug 2 (D3) in a ratio 10/1/1 to 10/1/10 (v/v/v).
      The solutions of morphine hydrochloride used were 10, 20, 30, 40 and 50 mg/ml
      prepared in water and isotonized with sodium chloride or dextrose. The drug
      solutions were used undiluted and diluted 1/5 (v/v) in water. All admixtures were
      prepared by adding the corticosteroid as D2 and as D3 in order to evaluate the
      influence of the order of mixing on the compatibility. The stability of the drugs
      in the compatible admixtures was evaluated during storage for 28 days at 22
      degrees C and protected from light. Visual inspection, high performance liquid
      chromatography (HPLC) analysis, pH and osmolality determinations were performed.
      For each drug combination incompatibility was observed with increasing ratio
      and/or concentration of the drug solutions. Within the range of compatibility the
      concentrations of the three drugs could be increased so to allow adequate symptom
      control with all drug combinations. For a similar admixture a higher
      concentrations of corticosteroid could be obtained using dexamethasone-21-sodium
      phosphate versus methylprednisolone-21-sodium succinate and a higher
      concentration of dexamethasone-21-sodium phosphate could be obtained without
      incompatibility using Decadron Pack versus Decadron. The admixtures for which the
      stability was evaluated were stable for 28 days (> 95% of the initial
      concentration). None of these admixtures showed any visual changes during
      storage, except for some of the admixtures prepared using undiluted Decadron, in
      which small crystals were seen after 1-28 days. The initial pH of the admixture
      ranged from 3.99 to 6.06 and varied less than 0.10 during storage. The initial
      osmolality of the admixtures ranged from 170 to 323 mOsm/kg and remained almost
      constant during storage.

PMID- 10205604
TI  - Aqueous ethyl cellulose dispersions containing plasticizers of different water
      solubility and hydroxypropyl methylcellulose as coating material for diffusion
      pellets. I. Drug release rates from coated pellets.
AB  - The present work investigates release mechanisms of theophylline pellets coated
      with an aqueous ethyl cellulose (EC) dispersion containing plasticizers and
      hydroxypropyl methylcellulose (HPMC) as a water soluble pore former. Three
      different drug release mechanisms from coated pellets can be determined as a
      function of the water solubility of the plasticizers and the ionic strength of
      the release medium. Coated pellets with the addition of more hydrophilic
      plasticizers such as triethyl citrate (TEC) or diethyl phthalate (DEP) show an
      approximate zero-order-release rate. In contrast, two-phase release profiles can
      be observed from pellets coated with dispersions containing hardly soluble
      plasticizers such as dibutyl phthalate (DBP) or dibutyl sebacate (DBS). Only in a
      release medium of high ionic strength the water soluble pore former will remain
      in the coating. Thus the drug diffuses through a hydrated swollen membrane
      containing EC, HPMC and insoluble plasticizer. The release mechanisms depend on
      the glass transition temperature of the ethyl cellulose and therefore on the
      migration of the plasticizers and the pore former. This was shown by
      investigation of the migration of the additives and the influence of the
      temperature of the release medium on the release. Additionally, the study
      investigates the effect of curing and storage conditions of coated pellets on the
      drug release rate.

PMID- 10205605
TI  - Influence of the moisture on the performance of a new dry powder inhaler.
AB  - An accelerated stability test was carried out on two prototypes of a new dry
      powder inhaler (DPI) to verify the influence of moisture uptake on the
      performance of the device. The prototypes were stored at 40 degrees C and 75%
      relative humidity (RH) for different storage times and their performance was
      assessed in terms of emitted dose and respirable fraction (Twin Impinger). At the
      same time intervals, the water content of the powder contained in the drug
      reservoir was evaluated using Karl Fischer's method. The respirable fraction was
      strongly influenced by the moisture content of the powder, on the contrary, the
      dosing precision and reproducibility is independent of this variable. The results
      show that a suitable protection from the external environment is necessary to
      prevent moisture uptake in the powder and the consequent loss of efficiency of
      the delivery device.

PMID- 10205606
TI  - Comparison of various cosolvency models for calculating solute solubility in
      water-cosolvent mixtures.
AB  - Previously published cosolvency models are critically evaluated in terms of their
      ability to mathematically correlate solute solubility in binary solvent mixtures
      as a function of solvent composition. Computational results show that the
      accuracy of the models is improved by increasing the number of curve-fit
      parameters. However, the curve-fit parameters of several models are limited. The
      combined nearly ideal binary solvent/Redlich-Kister, CNIBS/R-K, was found to be
      the best solution model in terms of its ability to describe the experimental
      solubility in mixed solvents. Also resented is an extension of the mixture
      response surface model. The extension was found to improve the correlational
      ability of the original model.

PMID- 10205607
TI  - Use of Caco-2 cells and LC/MS/MS to screen a peptide combinatorial library for
      permeable structures.
AB  - The transepithelial transport of a synthetic peptide combinatorial library
      containing 375,000 individual peptides was assessed using Caco-2 cell monolayers
      in order to screen for permeability and deliverability. A series of 150 pools,
      each containing 2500 tripeptide sequences, were applied to the apical side of
      Caco-2 monolayers. Basolateral side samples were collected after 4 h and screened
      by capillary high-pressure liquid chromatography. The majority of pools showed no
      permeable species, due to low solubility, limited permeability and extensive
      metabolism. Several pools contained permeable structure, and transport proved
      reproducible with passage number and time. Permeable structures were identified
      by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS). To
      discriminate between isobaric structures, several tripeptides were resynthesized
      and tested as discrete compounds. For example, 1-2% D-Phe-D-Ala-D-Ser-OH was
      transported across the Caco-2 cell monolayer with a Papp value of 0.35-0.69 x 10(
      6) cm/s, which is comparable with the permeability of amino acids (Leu, Papp =
      0.30 x 10(-6) cm/s) and dipeptides (L-Val-L-Val, Papp = 0.18 x 10(-6) cm/s)
      (Lennernas, H., Palm, K., Fagerholm, U., Artursson, P., 1996. Comparison between
      active and passive drug transport in human intestinal epithelial (Caco-2) cells
      in vitro and human jejunum in vivo. Int. J. Pharm. 127, 103-107; Tamura, K.,
      Bhatnagar, P.K., Takata, J.S., Lee, C.P., Smith, P.L., Borchardt, R.T., 1996.
      Metabolism, uptake, and transepithelial transport of the diastereomers of Val-Val
      in the human intestinal cell line Caco-2. Pharm. Res. 13, 1213-1218). These
      studies demonstrate the techniques used to screen combinatorial libraries for
      permeability across Caco-2 cells and structurally identify the resulting
      compounds. Such methodology can be of importance in the achievement of structure
      permeability relationships, useful in the design of pharmaceutically bioavailable
      drugs.

PMID- 10205608
TI  - Prediction of dissolution-absorption relationships from a dissolution/Caco-2
      system.
AB  - While the analysis of in vitro dissolution-in vivo absorption relationships from
      oral solid dosage forms provides biopharmaceutical insight and regulatory
      benefit, no well developed method exists to predict dissolution-absorption
      relationships a priori to human studies. The objective was to develop an
      integrated dissolution/Caco-2 system to predict dissolution-absorption
      relationships, and hence the contributions of dissolution and intestinal
      permeation to overall drug absorption for fast and slow formulations of
      piroxicam, metoprolol, and ranitidine. Dissolution studies were conducted on fast
      and slow dissolving immediate-release formulations of piroxicam, metoprolol
      tartrate, and ranitidine HCl. Dissolution samples were treated with concentrated
      buffers to render them suitable (i.e., isotonic and neutral pH) for Caco-2
      monolayer permeation studies. The dissolution/Caco-2 system yielded a predicted
      dissolution-absorption relationship for each formulation which matched the
      observed relationship from clinical studies. The dissolution/Caco-2 system's
      prediction of dissolution or permeation rate-limited absorption also agreed with
      the clinical results. For example, the dissolution/Caco-2 system successfully
      predicted the slow piroxicam formulation to be dissolution rate-limited, and the
      fast piroxicam formulation to be permeation rate-limited. Moreover, the system
      predicted this change from dissolution rate-limited absorption for slow piroxicam
      to permeation rate-limited absorption for fast piroxicam, in spite of piroxicam's
      high permeability and low solubility. The dissolution/Caco-2 system may prove to
      be a valuable tool in formulation development. Broader evaluation of such a
      system is warranted.

PMID- 10205609
TI  - Comments concerning: solubility prediction of caffeine in aqueous N,N
      dimethylformamide mixtures using the extended Hildebrand solubility approach.

PMID- 10205610
TI  - Surfactants in membrane solubilisation.
AB  - An understanding of the action of many drugs requires a knowledge of how the drug
      reaches the site of action in a cell. A detailed knowledge of the structure and
      function of cell membranes is often required to understand the transport of drugs
      across the plasma membrane. To obtain this information proteins must be isolated.
      The isolation and characterisation of cell membrane proteins usually requires the
      solubilisation of the membrane and a method of separation of the various membrane
      proteins and glycoproteins. The starting point for such an investigation is the
      choice of a suitable surfactant (detergent) to solubilise the membrane. This
      review considers the range of surfactants that are available for membrane
      solubilisation, how surfactants interact with membranes, the part they play in
      the separation of integral membrane proteins and in the reconstitution of
      membrane proteins for functional studies. The solubilisation of specific membrane
      proteins and glycoproteins including the human erythrocyte anion transporter,
      mitochondrial porin, sarcoplasmic reticulum Ca(2+)-ATPase, the ATPase-active
      multidrug transporter P-glycoprotein, bacteriorhodopsin and rhodopsin are also
      discussed.

PMID- 10205611
TI  - Mucoadhesion of polystyrene nanoparticles having surface hydrophilic polymeric
      chains in the gastrointestinal tract.
AB  - The mucoadhesion of polystyrene nanoparticles having surface hydrophilic
      polymeric chains in the gastrointestinal (GI) tract was investigated in rats.
      Radiolabeled nanoparticles were synthesized by adding hydrophobic 3
      (trifluoromethyl)-3-(m-[125I]iodophenyl)diazirine in the final process of
      nanoparticle preparation. The radioiodonated diazirine seemed to be incorporated
      in the hydrophobic polystyrene core of nanoparticles. The incorporation rate was
      less than 10%, irrespective of nanoparticle type. The diazirine incorporated in
      nanoparticles exhibited little leakage from them even though they were mixed with
      a solution corresponding to GI juice. The change in blood ionized calcium
      concentration after oral administration of salmon calcitonin (sCT) with
      nanoparticles showed that the in vivo enhancement of sCT absorption by
      radiolabeled nanoparticles was the same as that by non-labeled nanoparticles. The
      GI transit rates of nanoparticles having surface poly(N-isopropylacrylamide),
      poly(vinylamine) and poly(methacrylic acid) chains, which can improve sCT
      absorption, were slower than that of nanoparticles covered by poly(N
      vinylacetamide), which does not enhance sCT absorption at all. These slow transit
      rates were probably the result of mucoadhesion of nanoparticles. The strength of
      mucoadhesion depended on the structure of the hydrophilic polymeric chains on the
      nanoparticle surface. The mucoadhesion of poly(N-isopropylacrylamide)
      nanoparticles, which most strongly enhanced sCT absorption, was stronger than
      that of ionic nanoparticles, and poly(N-vinylacetamide) nanoparticles probably
      did not adhere to the GI mucosa. These findings demonstrated that there is a good
      correlation between mucoadhesion and enhancement of sCT absorption.

PMID- 10205612
TI  - Effect of compressional force on the crystallinity of directly compressible
      cellulose excipients.
AB  - The effect of compressional force on the crystallinity of low crystallinity
      cellulose (LCPC), microcrystalline celluloses (Avicel PH-101, PH-102 and PH-302
      grades) and powdered cellulose (Solka Floc BW-100) has been investigated using an
      X-ray diffraction method. Microcrystalline and powdered celluloses showed an
      increase of about 10% in their crystallinities, compared to the values for the
      corresponding powders, at a compression pressure of 5-10 MPa. The increase in the
      crystallinity of LCPC was gradual and reached the maximum value of 5% at a
      compression pressure of 15 MPa. Further increase in compression pressure (to 77
      MPa) had no effect on the crystallinity of LCPC, Avicel PH-101, Avicel PH-302 and
      Solka Floc BW-100. Avicel PH-102, on the other hand, showed a decrease in
      crystallinity at 15 MPa. Beyond 15 MPa, however, no statistically significant
      change in the crystallinity of the product was noted.

PMID- 10205613
TI  - The use of energy indices in estimating powder compaction functionality of
      mixtures in pharmaceutical tableting.
AB  - A series of binary powder blends comprising of microcrystalline cellulose (Avicel
      PH101), alpha-lactose monohydrate or theophylline anhydrous were prepared in
      order to investigate the densification of binary pharmaceutical powder mixes
      under compaction pressure. It is postulated that the use of derived energy
      parameters, as well as various evolved indices, calculated from the work expended
      during the fabrication and/or rupture of a compact can be employed to
      quantitatively predict the compaction properties of pharmaceutical powder mixes
      comprised of the same constituents. The relationship between the net work of
      compression normalized to powder volume and the resulting compact strength for
      mix constituents can be used to define a pharmaceutical formulation space in
      which compact mechanical properties can be estimated for other 'virtual mixes' of
      the same constituents in different proportions. The approach is successfully
      applied to the prediction of the mechanical properties of a ternary mix of these
      constituents.

PMID- 10205614
TI  - Mucoadhesive buccal disks for novel nalbuphine prodrug controlled delivery:
      effect of formulation variables on drug release and mucoadhesive performance.
AB  - The objective of this work was to assess the effects of drug solubility and
      loading percent, as well as Carbopol 934/hydroxypropylcellulose (CP/HPC) ratio,
      on drug release and mucoadhesive performance of the nalbuphine prodrug loaded
      buccal disks. Drug release rates for the disks were found to be a function of
      drug solubility, with higher drug release rates for disks loaded with more
      hydrophilic prodrugs and an increased amount of beta-cyclodextrin. The drug
      release rates increased with loading percents for nalbuphine hydrochloride,
      whereas an opposite drug release trend was observed for disks loaded with
      nalbuphine enanthate, which can be explained by the diffusional drug release
      mechanism. The CP/HPC ratio affected release rates of nalbuphine enanthate,
      whereas the ratio had no impact on the release of nalbuphine hydrochloride.
      Within the 2 days of experiment time, all formulations attached well to the
      porcine buccal tissues, indicating those formulation variables had no influence
      on the mucoadhesive performance of CP/HPC-based buccal disks.

PMID- 10205615
TI  - Influence of physicochemical and biological parameters on drug release from
      microspheres adhered on vesical and intestinal mucosa.
AB  - The object of our work is to develop mucoadhesive microspheres to be applied into
      the urinary bladder. In the present study the microspheres were prepared and the
      release of a model drug after their adhesion to mucosa was evaluated. The
      microspheres were prepared by solvent evaporation method using Eudragit RL or
      hydroxypropylcellulose as matrix polymers and one out of five different polymers
      as mucoadhesives or non-mucoadhesive references. A method for the evaluation of
      the drug release from microspheres adhered on guinea pig urinary bladder and
      small intestine mucosa was developed and the influence of the following
      parameters on this process was followed: mucoadhesion strength of polymeric
      films, swelling of polymers and the drug release from microspheres. The results
      showed that the detachment forces were decreasing in the following order: CMCNa >
      Carbopol 934P > HPC > EE.HCl = PVP/VA. Carbopol swelled to the largest volume
      among all polymers and the drug release from microspheres was more retarded when
      Eudragit RL was used as matrix polymer. When comparing the results of pipemidic
      acid release from microspheres adhered on intestinal mucosa with detachment
      forces, similar ratios among the mucoadhesive polymers can be seen. On the other
      hand, differences between two mucosae were observed. These differences are due to
      the amount of mucus on mucosa and might also be influenced by the charge of
      mucus. The goal of our work at this point of investigation was achieved by
      microspheres containing carboxymethylcellulose as mucoadhesive and Eudragit RL as
      matrix polymer because they provide the longest release time from microspheres
      adhered on vesical mucosa and sufficient high strength of mucoadhesion.

PMID- 10205616
TI  - Formation of ondansetron polymorphs.
AB  - We used differential scanning calorimetry, infrared spectrophotometry and 1H
      nuclear magnetic resonance imaging to search for polymorphs of ondansetron.
      Samples were tested under different conditions of temperature, pulverization and
      pH, and in different solvents. The factors identified as able to cause the
      formation of polymorphs were heating to different temperatures for different
      times, and the use of ethanol and methanol as solvents.

PMID- 10205617
TI  - Examples of successful crystal structure prediction: polymorphs of primidone and
      progesterone.
AB  - The field of crystal structure prediction and its potential value to the
      pharmaceutical industry is described. The process of structure prediction
      employed here is summarized and the results of its application to primidone and
      progesterone are reported. It is shown that the process successfully generates
      the known polymorphs of these molecules, starting from the molecular structure
      alone. Observations related to the application of the structure prediction
      process are reported.

PMID- 10205618
TI  - The characterization and release kinetics evaluation of baclofen microspheres
      designed for intrathecal injection.
AB  - Baclofen, a water soluble drug advocated for the treatment of spinal spasticity,
      was microencapsulated, using the oil/water emulsion extraction process in an
      attempt to identify the appropriate experimental conditions capable of producing
      microspheres releasing baclofen over 2-4 weeks. Individual microspheres ranging
      in size from 15 to 30 microns were formed exhibiting smooth surfaces at low drug
      payload (12.8% w/w), irregular and rough surface at high drug content (33.9%
      w/w). The microencapsulation yield remained practically unchanged (85-90%) up to
      theoretical payloads of 37.5% w/w, and decreased markedly to 70% when the initial
      theoretical payload was 50% w/w. The in vitro release profile of baclofen from
      the poly(D,L-lactide-co-glycolide) microspheres was biphasic only for the high
      drug payload microspheres with a rapid release of 70% within 48 h, followed by a
      slower release rate over at least 25 days. In contrast, the microspheres
      containing low baclofen contents (12.8% w/w) exhibited a gradual and progressive
      release rate over the course of the experiment. The baclofen release data did not
      fit either the general equation which describes the diffusional release of
      dispersed tiny drug particles from spherical micromatrices, or to the kinetic
      equations which describe the release of dissolved drug from monolithic
      microspherical devices. It appears that the release of baclofen from the present
      microspheres is not governed by a unique mechanism. This should be attributed
      either to the presence of some uncoated drug particles or to the large size of
      the embedded drug particles compared with the relatively small size of the
      spherical micromatices, or to some polymeric erosion occurring after several days
      incubation in the release medium.

PMID- 10205619
TI  - Studies on the stability of trans-alpha-acetoxytamoxifen in Sprague-Dawley female
      rat liver slices, homogenate and subcellular fractions including microsomes and
      mitochondria.
AB  - This work examined the stability of trans alpha-acetoxytamoxifen in Krebs
      Henseleit buffer (pH 7.4), in the presence of Sprague-Dawley female rat liver
      slices, rat liver homogenate and hepatic subcellular fractions, including
      microsomes and mitochondria, at pH 7.4 and at 37 degrees C over 300 min. The rate
      of hydrolysis was determined using high-performance liquid chromatography, and
      degradation profiles were obtained from which the rate and order of degradation
      were both evaluated. By applying zero-, first-, second- and third-order models of
      drug disappearance and the generation of by-products, first- and second-order
      appeared to produce the best fit. trans-alpha-Acetoxytamoxifen degraded rapidly
      in buffer and more slowly in the biological systems, probably due to the fact
      that the agent partitions into the hydrophobic component of the biological tissue
      and hence degrades at a much slower rate. The principal degradation products were
      trans-alpha-hydroxytamoxifen and, to a lesser extent, cis-alpha-hydroxytamoxifen.
      Another peak could not be identified. The production of trans-alpha
      hydroxytamoxifen was enhanced in the presence of biological enzymes, whereas the
      concentration of the cis isomer remains relatively constant in buffer only (pH
      7.4) and in the presence of biological enzymes. Therefore, the formation of
      identical adducts with DNA is consistent, because it has been shown that alpha
      acetoxytamoxifen breaks down to form alpha-hydroxytamoxifen in vitro. The
      percentage of trans-alpha-acetoxytamoxifen remaining after 300 min was 40% in
      mitochondria and 32% in homogenate. The half-life (t1/2) was calculated for each
      condition by applying zero-, first- and second-order rate kinetics.

PMID- 10205620
TI  - Suppression of agglomeration in fluidized bed coating. II. Measurement of mist
      size in a fluidized bed chamber and effect of sodium chloride addition on mist
      size.
AB  - It has been reported that the degree of particle agglomeration in fluidized bed
      coating is greatly affected by the spray mist size of coating solution. However,
      the mist size has generally been measured in open air, and few reports have
      described the measurement of the mist size in a chamber of the fluidized bed, in
      which actual coating is carried out. Therefore, using hydroxypropylmethyl
      cellulose (HPMC) aqueous solution as a coating solution, the spray mist size of
      the coating solution in a chamber of the fluidized bed was measured under various
      coating conditions, such as the distance from the spray nozzle, fluidization air
      volume, inlet air temperature and addition of sodium chloride (NaCl) into the
      coating solution. The mist size in the fluidized bed was compared with that in
      open air at various distances from the spray nozzle. Further, the relationship
      between the spray mist size and the degree of suppression of agglomeration at
      various NaCl concentrations during fluidized bed coating was studied. The mist
      size distribution showed a logarithmic normal distribution in both cases of the
      fluidized bed and open air. The number-basis median diameter of spray mist (D50)
      in the fluidized bed was smaller compared with that in open air. D50 increased
      with the increasing distance from the spray nozzle in both cases. In the
      fluidized bed, D50 decreased with the increasing fluidization air volume and
      inlet air temperature. The effect of NaCl concentration on the mist size was
      hardly observed, but the degree of suppression of agglomeration during coating
      increased with the increasing NaCl concentration in the coating solution.

PMID- 10205621
TI  - Formulation and evaluation of controlled release Eudragit buccal patches.
AB  - Controlled release buccal patches were fabricated using Eudragit NE40D and
      studied. Various bioadhesive polymers, namely hydroxypropylmethyl cellulose,
      sodium carboxymethyl cellulose and Carbopol of different grades, were
      incorporated into the patches, to modify their bioadhesive properties as well as
      the rate of drug release, using metoprolol tartrate as the model drug. The in
      vitro drug release was determined using the USP 23 dissolution test apparatus 5
      with slight modification, while the bioadhesive properties were evaluated using
      texture analyzer equipment with chicken pouch as the model tissue. The
      incorporation of hydrophilic polymers was found to affect the drug release as
      well as enhance the bioadhesiveness. Although high viscosity polymers can enhance
      the bioadhesiveness of the patches, they also tend to cause non-homogeneous
      distribution of the polymers and drug, resulting in non-predictable drug-release
      rates. Of the various bioadhesive polymers studied, Cekol 700 appeared to be most
      satisfactory in terms of modifying the drug release and enhancement of the
      bioadhesive properties.

PMID- 10205622
TI  - Enhanced transport of nanoparticle associated drugs through natural and
      artificial membranes--a general phenomenon?
AB  - The transport of nanoparticle associated drugs, [75Se]norcholestenol, captopril,
      methylene blue, hydrocortisone, doxorubicin, and dalargin was determined by
      permeability measurements in two chamber side by side diffusion cells using
      cellulose acetate, silicone rubber, pig small intestine, or hairless mice skin as
      membranes. Solutions of free drugs served as controls. The permeabilities
      depended on the physico chemical properties of the drugs which governed both,
      drug interaction with the nanoparticles as well as with the membranes.
      Consequently, the influence of dilution of the nanoparticle or free drug
      preparations on permeabilities was complex. With the exception of
      [75Se]norcholestenol the permeabilities were higher with free drugs than after
      binding to nanoparticles. The permeabilities of the membranes decreased in the
      order cellulose acetate, pig small intestine, silicone rubber, and hairless mouse
      skin.

PMID- 10205623
TI  - Toxicity of gamma irradiated liposomes. 1. In vitro interactions with blood
      components.
AB  - Gamma irradiation is a potential technique for sterilisation of liposome
      suspensions. Unfortunately, gamma irradiation may result in chemical degradation
      of the phospholipids and the toxicological aspects have to be considered. The
      effects of liposome composition and gamma irradiation on the interactions of the
      liposomes with the hemostatic mechanisms (hemolysis, aggregation and coagulation)
      were studied. Non-irradiated liposome suspensions showed no hemolysis of
      erythrocytes. After irradiation, up to 3.1% hemolysis was measured. Least
      hemolysis was observed with irradiated liposomes composed of unsaturated or
      charged phospholipids. The negatively charged DSPG-liposomes (both non-irradiated
      and irradiated) induced aggregation of platelets as observed by the
      spectrophotometric method. However, no aggregates were seen in the microscope or
      measured by the aggregometer. Negatively charged liposomes also affected the
      coagulation cascade where prolonged coagulation times were measured. Irradiation
      of the liposome suspensions resulted in even longer coagulation times. The
      prolonged coagulation times correlated to some extent with the measured binding
      and depletion of calcium from plasma by the negatively charged liposomes.

PMID- 10205624
TI  - Toxicity of gamma irradiated liposomes. 2. In vitro effects on cells in culture.
AB  - In this study, the effects of liposome composition and gamma irradiation on their
      interactions with cell cultures were studied. The cytotoxicity test and the
      growth inhibition test clearly revealed toxic effects of liposomes composed of
      unsaturated phospholipids and gamma irradiation of these preparations enhanced
      their toxic effects. The murine fibroblast cell-line L 929 was less affected
      compared to the macrophage cell-line RAW 264 with a higher endocytic capacity. On
      the other hand, both gamma irradiated and non-irradiated liposomes composed of
      saturated phospholipids were non-toxic for the cells and irradiation did not
      affect their drug delivery properties. Hence, it seems that gamma irradiation is
      appropriate for sterilisation of these liposomes.

PMID- 10205625
TI  - Evaluation of the clearance characteristics of bioadhesive systems in humans.
AB  - This paper describes the characterisation, radiolabelling and clearance
      characteristics of three bioadhesive nasal delivery systems; starch microspheres,
      chitosan microspheres and chitosan solution. The time taken for 50% of these
      bioadhesive materials and a control to be cleared from the nasal cavity, after
      nasal administration to human volunteers, was evaluated using gamma scintigraphy.
      The data show that the control was cleared rapidly, with a half life of 21 min,
      whereas the bioadhesive delivery systems had much longer half lives. The
      clearance of the chitosan solution almost doubled to 41 min, whilst the half life
      of clearance for the starch microspheres more than tripled to 68 min and for the
      chitosan microspheres the half life of clearance quadrupled to 84 min. From the
      results reported in this study it is possible to determine that both chitosan
      systems and the starch microspheres have good bioadhesive characteristics. The
      results have supported the hypothesis that chitosan delivery systems can reduce
      the rate of clearance from the nasal cavity, thereby increasing the contact time
      of the delivery system with the nasal mucosa, providing the potential for
      increasing the bioavailability of drugs incorporated into these systems.

PMID- 10205626
TI  - Influence of ionic strength on drug adsorption onto and release from a
      poly(acrylic acid) grafted poly(vinylidene fluoride) membrane.
AB  - Ion exchange resins have several applications in pharmacy for controlled or
      sustained release of drugs. In the present study, effects of the ionic strengths
      of adsorption medium and dissolution medium on drug adsorption onto and release
      from a acrylic acid grafted poly(vinylidene fluoride) (PAA-PVDF) were studied.
      Despite their porosity, PAA-PVDF membranes act reasonable well as cation exchange
      membranes. It was observed, that ionic strength of adsorption medium, degree of
      grafting and concentration of propranolol-HCl in adsorption medium affect
      propranolol-HCl adsorption onto the membrane. The fluxes of smaller molecules (MW
      < 500) across the membrane decreased with ionic strength of buffer solution,
      whereas the fluxes of the large molecules (FITC-dextran, MW 4400) increased with
      ionic strength. Release rate of adsorbed propranolol-HCl from the membrane into
      phosphate buffer was greatly affected by ionic strength of adsorption medium.
      These results can be explained by a cation exchange process between membrane and
      cations present in the buffer solution and swelling behavior of the grafted PAA
      chains.

PMID- 10205627
TI  - Compatibility of paclitaxel in 5% glucose solution with ECOFLAC low-density
      polyethylene containers-stability under different storage conditions.
AB  - The compatibility of paclitaxel with low-density polyethylene containers
      (ECOFLAC) was studied under different temperature and light conditions. Solutions
      of 0.4 and 1.2 mg/ml of paclitaxel in 5% glucose solution were prepared, put into
      ECOFLAC containers and stored: (i) at ambient temperature (20-25 degrees C) and
      in ambient light; (ii) at ambient temperature in the dark; and (iii) at +4
      degrees C in the dark. Paclitaxel was assayed by high-performance liquid
      chromatography after visual inspection of the solutions. The results show that
      solutions of TAXOL in 5% glucose should not be stored for more than 5 days in
      glass or ECOFLAC containers because a whitish precipitate tends to form, lowering
      the paclitaxel concentration. The decrease in the paclitaxel concentration
      observed after chromatographic analysis ranged very widely (from 12 to 83% of the
      initial concentration). However solutions of TAXOL diluted in 5% glucose was
      stable for 5 days in ECOFLAC containers under all the storage conditions tested.
      These additive-free low-density polyethylene containers offer the advantage of
      not releasing DEHP into the paclitaxel solutions.

PMID- 10205628
TI  - Transdermal iontophoretic delivery of diclofenac sodium from various polymer
      formulations: in vitro and in vivo studies.
AB  - The objective of this study was to evaluate the in vitro and in vivo transdermal
      iontophoresis of various diclofenac sodium polymer formulations. The excised rat
      skin, human skin as well as cellulose membrane were used to examine the in vitro
      drug permeation whereas the microdialysis technique was used to monitor the drug
      concentration in vivo. Polymer solutions based on polyvinylpyrrolidone (PVP) and
      hydroxypropyl methylcellulose (HPMC) binary system showed higher drug
      permeability than that of single polymer vehicle. The effect of formulations on
      drug permeation through cellulose membrane was quite different from those through
      rat skin and human skin, which can be explained by the different permeation
      pathways between them. It appeared to be a membrane-controlled mechanism but not
      the vehicle matrix-controlled mechanism for diclofenac hydrogels when using skin
      as the diffusion barrier. The recovery of diclofenac sodium in the in vivo
      microdialysis was approximately 80-90%, indicating this technique can be used in
      the intradermal drug monitoring. For all the polymer formulations tested, there
      was a good relationship between the in vitro and in vivo drug permeation. A
      synergistic effect on drug permeation was observed when transdermal iontophoresis
      combined with the pretreatment of cardamom oil as a permeation enhancer.

PMID- 10205629
TI  - Investigations into the reduction of powder adhesion to stainless steel surfaces
      by surface modification to aid capsule filling.
AB  - The adhesion force of powder particles to stainless steel surfaces, which had
      been modified by various metal coatings, has been measured using a centrifuge
      technique. The surfaces were characterised by surface roughness and surface free
      energy measurements, whereas the particles, which had a particle size of 32-45
      microns, were characterised by their surface free energy only. The roughness of
      the surfaces was found to be similar, so that changes in the adhesion properties
      of the powders to these surfaces could not be due to a change in this surface
      property. However, there was a major difference in the surface free energy
      parameters of the surfaces. The surface free energy varied from a nearly non
      polar character to strong Lewis-base. The adhesion force of pregelatinised starch
      and lactose monohydrate particles increased with the increasing base character of
      the surfaces. In principle this behaviour could also be seen for calcium
      carbonate particles. However, here the order of the adhesion forces to the
      surfaces tested was disrupted on one occasion because of a pronounced influence
      of particle and surface hardness on this property. In general, the ranking of the
      adhesion forces matched observations made during capsule filling on a Bosch GKF
      400 tamp-filling machine. It was therefore concluded that a metal coating of the
      tamping pins would be able to reduce powder adhesion. In order to identify the
      best coating, centrifugal adhesion force measurements could be undertaken, or
      surface free energy measurements could be made. The results found suggest that a
      surface finish by means of chromium nitride coating provided, in most cases, a
      significant reduction of the powder adhesion. For very hard powder particles such
      as inorganic excipients the hardness of the surfaces must also be increased. In
      these cases plasma-coating of chromium appears helpful.

PMID- 10205630
TI  - Influence of formulation on jet nebulisation quality of alpha 1 protease
      inhibitor.
AB  - As foam appears during solution constitution and nebulisation of alpha 1 protease
      inhibitor (alpha 1 PI), we selected in a previous work, antifoams likely to be
      associated with an alpha 1 PI solution to be nebulised: span 65 at a 0.025%
      concentration and cetyl alcohol at a 0.05% concentration associated with
      tyloxapol at 0.025% concentration. The purpose of this study was, on the one hand
      to study the influence of the formulation on nebulisation quality by relating
      physicochemical properties and nebulisation capacity, and on the other hand, to
      define the alpha 1 PI that will be retained for a clinical study. The properties
      of the different alpha 1 PI formulations are compared: surface tension,
      viscosity, time required to constitute the protein solution and pH. Nebulisation
      quality is evaluated under different operating conditions by measuring the
      droplet size, the quantity of alpha 1 PI nebulised, nebulisation time and the
      quantity of alpha 1 PI likely to reach the lungs which was subjected to
      statistical analysis. The statistical analysis of results indicates that the
      addition of the cetyl alcohol/tyloxapol mixture improves nebulisation
      effectiveness by significantly increasing the quantity of drug nebulised and
      therefore the quantity of alpha PI likely to reach the lungs. It is this
      formulation that will be retained for clinical trials. We check that the
      nebuliser and operating conditions influence all the parameters, that is to say
      the respirable fraction, the quantity nebulised and the nebulisation time.
      Although there is no interaction between the nebuliser and the formulation,
      nebulisation quality is the combined result of the formulation, the nebuliser and
      the operating conditions.

PMID- 10205631
TI  - Properties of the racemic species of verapamil hydrochloride and gallopamil
      hydrochloride.
AB  - It is well known that the stereoselective actions associated with the
      enantiomeric constituents of a racemic drug can differ markedly in their
      pharmacodynamic or pharmacokinetic properties. Nevertheless, molecular chirality
      manifests itself in the solid, that is, crystalline state. The aim of this work
      was to characterize the solid-state properties of verapamil HCl and gallopamil
      HCl, two well-known chiral calcium channel antagonists. The characterization of
      the solid state for the single enantiomers and equimolecular mixtures for both
      the calcium antagonists was performed by solid-state techniques such as Fourier
      transform infrared (FT-IR spectroscopy), X-ray powder diffractometry (XRD) and
      differential scanning calorimetry (DSC). The FT-IR spectra and XRD of the single
      enantiomers are different from those of the corresponding equimolecular mixture
      owing to their different crystalline structure. The thermal behavior of the
      racemates and pure enantiomers were examined by DSC, and the resultant
      experimental and theoretical binary phase diagrams are discussed. Spectroscopic
      solid-state techniques, such as FT-IR and XRD, are useful in combination with
      thermal analysis for characterizing the racemic species of chiral drugs. The data
      obtained prove that the equimolecular mixtures of both verapmil hydrochloride and
      gallopamil hydrochloride exist as racemic compounds. Determination of the
      enantiomeric purity of the enantiomers and racemic compounds of both the calcium
      antagonists analyzed was performed by DSC.

PMID- 10205632
TI  - Transdermal iontophoretic delivery of methylphenidate HCl in vitro.
AB  - Methylphenidate is prescribed orally for Attention Deficit Disorder in children
      and adults, and for narcolepsy patients. Methylphenidate has a short plasma half
      life (1-2 h) and thus needs to be frequently administered for effective therapy.
      Such therapy has limitations in terms of patient compliance, particularly in
      young children. For such reasons, the development of a transdermal dosage form of
      methylphenidate may be useful. This study was undertaken to evaluate the passive
      and electrically assisted transport (iontophoresis) of methylphenidate from
      aqueous methylphenidate hydrochloride solutions across excised human skin. A
      maximum flux of 12.0 micrograms/(cm2 h) of protonated methylphenidate was
      estimated from the passive transport data at pH 3.5. Iontophoresis significantly
      enhanced protonated methylphenidate transport as compared with passive delivery.
      From the present experiments, the efficiency of iontophoretic delivery of
      methylphenidate was approximately 700 micrograms/(mA h). Based on in vitro skin
      flux data, the daily dose of 15-40 mg methylphenidate can be achieved using a
      current density of 0.5 mA/cm2 and a minimum transport area of 2-5 cm2 for 24-h
      application, or an area of 4-10 cm2 for 12-h (daytime) application. From
      methylphenidate skin flux values, methylphenidate mobility of 2.2 x 10(-4) cm2/(V
      s) was estimated, which compares reasonably with its free solution mobility of
      6.6 x 10(-4) cm2/(V s).

PMID- 10205633
TI  - Effect of the formulation on the in-vitro release of propranolol from gellan
      beads.
AB  - Gellan gum beads of propranolol hydrochloride, a hydrophilic model drug, were
      prepared by solubilising the drug in a dispersion of gellan gum and then dropping
      the dispersion into calcium chloride solution. The droplets formed gelled beads
      instantaneously by ionotropic gelation. Major formulation and process variables
      which might influence the preparation of the beads and the drug release from
      gellan gum beads were studied. Very high entrapment efficiencies were obtained
      (92%) after modifying the pH of both the gellan gum dispersion and the calcium
      chloride solution. The beads could be stored for 3 weeks in a wet or dried state
      without modification of the drug release. Oven-dried beads released the drug
      somewhat more slowly than the wet or freeze-dried beads. The drug release from
      oven-dried beads was slightly affected by the pH of the dissolution medium.
      Gellan gum could be a useful carrier for the encapsulation of fragile drugs and
      provides new opportunities in the field of bioencapsulation.

PMID- 10205634
TI  - The formulation and stability of erythromycin-benzoyl peroxide in a topical gel.
AB  - The combination of benzoyl peroxide and erythromycin is used for the local
      treatment of acne and available as a commercial preparation. Because of the
      stability problems of erythromycin an extempore preparation is required. The
      influence of storage temperature and non active ingredients on the stability of
      benzoyl peroxide and erythromycin in topical gel preparations for extempore
      compounding is described. A microbiological and an HPLC method were used to
      determine the erythromycin and the benzoyl peroxide concentrations, respectively.
      For a formulation compounded with hydroxyethylcellulose no stability problems
      were observed. For the formulation containing Carbopol 940, the levels of
      erythromycin varied over a wide range due to precipitation and aggregation of the
      drug during compounding.

PMID- 10205635
TI  - Effect of penetration enhancers on the permeation of the thyrotropin releasing
      hormone analogue pGlu-3-methyl-His-Pro amide through human epidermis.
AB  - The effect of the enhancers, cineole and ethanol, on the transdermal penetration
      of the tripeptide, pGlu-3-methyl-His2-Pro amide (M-TRH), across human epidermal
      membrane was studied by flow-through diffusion chambers. The aim of the study was
      to assess whether the biologically active analogue M-TRH displays similar
      transdermal penetration properties as those demonstrated earlier for the parental
      peptide, thyrotropin-releasing hormone (TRH) (Magnusson et al., 1997a Int. J.
      Pharm. 157, 113-121). Steady-state fluxes with a donor solution of phosphate
      buffered saline (PBS) were 0.34 +/- 0.01 microgram/cm2h for M-TRH and 0.27 +/-
      0.01 microgram/cm2h for TRH. Measured over 30 h the total amount penetrated was
      8.6 +/- 1.0 and 7.8 +/- 1.7 micrograms/cm2, respectively. In the presence of 50%
      ethanol, the flux of the peptides increased approximately 3-fold. A donor
      solution of 3% cineole, in combination with 47% ethanol, increased the
      penetration of M-TRH to 1.60 +/- 0.02 micrograms/cm2h, compared to 0.92 +/- 0.03
      microgram/cm2h for TRH, as reported previously. The corresponding total amount
      penetrated over 30 h was 41.5 +/- 4.9 and 24.9 +/- 1.7 micrograms/cm2,
      respectively. Our data suggests that enhancers added together with the penetrant
      can theoretically induce changes in the permeability of the stratum corneum
      sufficient to promote the transdermal absorption of therapeutically relevant
      amounts of these peptides. This demonstrates the possibility to deliver classes
      of compounds that have been viewed as not suitable for transdermal
      administration.

PMID- 10205636
TI  - Species difference in simultaneous transport and metabolism of ethyl nicotinate
      in skin.
AB  - The objective of this research was to compare the characteristics of skin
      permeation and metabolism of ethyl nicotinate (EN) among humans and several
      animal models. In vitro simultaneous skin permeation and metabolism experiment of
      EN was done in side by side diffusion cells at 37 degrees C. An EN hydrolysis
      experiment was carried out using skin homogenate and kinetic parameters (Vmax and
      K(m)) were estimated by computer data-fitting to Michaelis-Menten equation. Both
      EN and a metabolite, nicotinic acid (NA), were detected in all receiver solutions
      in permeation studies and no significant chemical hydrolysis was found,
      indicating that enzymatic hydrolysis of EN occurred during the skin permeation
      process. Difference in total (EN + NA) flux, from EN-saturated solution, was less
      than double among various species. The ratio of NA flux to total flux was highest
      for rat (0.94) followed by hairless rat, mouse, human and hairless mouse (0.76,
      0.23, 0.19 and 0.13), and thus a great species difference was found in skin
      esterase activity. Total flux increased linearly with increase in donor
      concentration for all species. For hairless rat, mouse and hairless mouse, NA
      fluxes increased with increase in EN donor concentration and reached a plateau,
      suggesting that metabolic saturation occurred in skin. Species difference in NA
      fluxes and EN donor concentration in which the NA flux reached a plateau were
      also found. In rats, kinetic parameters for EN hydrolysis using skin homogenate
      were significantly higher than those in mice. These results suggest that species
      difference in permeation profiles of EN might primarily reflect the difference in
      esterase activity. To predict skin permeability in human using an animal model,
      the species difference in skin metabolism should be taken into consideration.

PMID- 10205637
TI  - The bioequivalence study of folifer-Z: a new formulation of sustained-release
      iron and zinc.
AB  - The bioequivalence of Folifer-Z tablets, a new sustained-release iron and zinc
      formulation was evaluated and compared to that of Fefol-Z capsules in 30 healthy
      male subjects. Each subject received a single oral dose of either product
      according to a randomized two-way crossover design. A washout period of 1 week
      was allowed after each treatment. Blood samples were obtained over a 24-h period,
      and iron and zinc concentrations were measured. The pharmacokinetic parameters of
      Folifer-Z were Cmax (103 +/- 46.2 micrograms/dl), Tmax (5.93 +/- 2.94 h) and AUC0
      24 h (1937 +/- 706 micrograms/dl per h), whereas the corresponding Fefol-Z values
      were Cmax (109 +/- 41.5 micrograms/dl), Tmax (6.64 +/- 2.54) and AUC0-24 h (1865
      +/- 699 micrograms/h per dl). Analysis of variance on log-transformed data for
      Cmax and AUC0-24 h revealed lack of significant differences among the two
      formulations. The mean relative bioavailability of AUCtest/AUCreference was 1.07
      (90% confidence interval range: 99-115%) and for Cmax test/Cmax reference was
      0.96 (90% confidence interval range: 88-105%). Regarding the zinc results, the
      pharmacokinetic parameters of Folifer-Z values were Cmax (101 +/- 20.7
      micrograms/dl), Tmax (4.86 +/- 1.53 h) and AUC0-24 h (1944 +/- 202 micrograms/h
      per dl), while the corresponding Fefol-Z values were Cmax (102 +/- 20.7), Tmax
      (4.93 +/- 1.51) and AUC0-24 h (1953 +/- 200). Analysis of variance on log
      transformed zinc data for Cmax, Tmax and AUC0-24 h revealed lack of significant
      difference among the two formulations. The mean relative bioavailability of
      AUCtest/AUCreference was 0.98 (90% confidence interval range; 95-101%) and for
      Cmax test/Cmax reference was 0.92 (90% confidence interval range: 89-96%). The
      results also indicate a possible inhibition of zinc absorption by iron content of
      both formulations. It is concluded that Folifer-Z product is bioequivalent to
      Fefol-Z product.

PMID- 10205638
TI  - Modified polypeptides containing gamma-benzyl glutamic acid as drug delivery
      platforms.
AB  - We previously reported the development of diffusion-controlled biodegradable
      polypeptides for drug delivery purposes. In this paper, we describe the synthesis
      of three modified polypeptides that contain gamma-benzyl glutamic acid as the
      common structural backbone. The properties of these polymers were characterized
      with regard to their potential application as drug delivery platforms.
      Procainamide hydrochloride, a hydrophilic drug, and protamine sulfate, a low
      molecular weight protein, were used as model drugs for examining release rate
      profiles from these polymers. The homopolymer of poly(gamma-benzyl-L-glutamic
      acid), PBLG, showed a highly helical configuration and a moderate release rate of
      procainamide. Modification of structural attributes by random copolymerization of
      the D- and L- isomers of gamma-benzyl glutamic acid produced poly(gamma-benzyl
      D,L-glutamic acid), PBDLG, which displayed a significantly slower release of
      procainamide when compared to PBLG. The modification of polymer bulk
      hydrophobicity by copolymerization of PBLG (A) with poly(ethylene glycol) (B)
      yielded an ABA triblock copolymer exhibiting much faster release rates for both
      procainamide and protamine than those demonstrated by the other two polymers.
      Using this triblock copolymer, protamine release rates ranging from 2 weeks to
      approximately 2 months were obtained by simply varying the polymer processing
      conditions and protein particle size. A nearly complete release of protein was
      obtained from the triblock copolymer blends and this occurred without reliance
      upon degradation of the polymer backbone. Fickian diffusion-controlled release
      mechanisms were implied for release of procainamide and protamine from these
      polypeptide formulations based on the linear relationship displayed between
      cumulative drug release and the square root of time.

PMID- 10205639
TI  - Solubility behavior of polymorphs I and II of mefenamic acid in solvent mixtures.
AB  - The dissolution profile and solubility of two polymorphic forms of mefenamic acid
      were studied in solvent mixtures of ethanol-water and ethyl acetate-ethanol. The
      solubility parameter (delta) was used to study the effect of polarity on the
      solubility behavior of the two polymorphs. Differential scanning calorimetry and
      infrared spectroscopy were performed on the original powders and on the solid
      phases after contact with the solvent systems for the characterization and
      identification of the polymorphs. The dissolution rates of both polymorphs is
      greater in the less polar mixtures (ethyl acetate-ethanol) of lower solubility
      parameter values. Form II showed larger dissolution rates and saturation
      concentrations than Form I in all the solvent systems studied. The solid phase of
      Form II converts totally to Form I after equilibration with the solvents. The
      rate of conversion was faster in the least polar mixtures. The solubility of both
      polymorphs reaches a single maximum at 80% ethyl acetate in ethanol, delta =
      20.09 MPa1/2. The modified extended Hildebrand method was used to predict the
      solubility profile of each polymorph. A single equation was obtained for both
      polymorphs which includes the solubility parameter of the mixtures and the
      logarithm of the solubility mole fraction of each polymorph in water. The
      Hildebrand solubility parameter of mefenamic acid is independent of the
      crystalline form and was determined from two methods giving quite similar values,
      delta 2 = 20-21 MPa1/2.

PMID- 10205640
TI  - Role of residual solvents in the formation of volatile compounds after
      radiosterilisation of cefotaxime.
AB  - Radiation sterilisation is a promising method to sterilise pharmaceutical
      products. However, this process is accompanied by a modification of odour due to
      volatile compounds formation. The origin of malodorous compounds produced during
      solid cefotaxime radiosterilisation has been investigated and several mechanisms
      are proposed to explain their appearance. Moreover, some quantitative data are
      given. Analysis of the degradation products was performed using a GC-ITD system
      with an injection by the static headspace technique. It appeared that some of the
      radio-induced compounds (such as carbon oxide sulfide and carbon disulfide) came
      from the degradation of the drug itself, whereas the formation of others required
      the presence of residual solvents which are volatile impurities already present
      before irradiation. Acetaldehyde directly came from impurities but the appearance
      of esters and acetaldehyde O-methyloxime was due to the presence of both
      cefotaxime and residual solvents together. Thus, the residual solvents play a key
      role in the radiolysis compounds formation (six of eight require the presence of
      them) and consequently in the modification of odour as well.

PMID- 10205641
TI  - Stability studies of a somatostatin analogue in biodegradable implants.
AB  - In recent years, peptides and proteins have received much attention as drug
      candidates. For many polypeptides, particularly hormones, it is desirable to
      release the drug continuously at a controlled rate over a period of weeks or even
      months, and thus a controlled release system is needed. Polylactic acid (PLA) is
      a biocompatible and biodegradable material with wide utility for many
      applications, including the design of controlled release systems for
      pharmaceutical agents. Pharmaceutical development of these delivery systems
      presents new problems in the area of stability assessment, especially for peptide
      drugs. In this study, we aimed to investigate the influence of different steps,
      during the manufacturing of an implant, on peptide stability in the polymeric
      matrix. Polylactic acid implants containing vapreotide, a somatostatin analogue,
      were prepared by extrusion. The effects of time, extrusion and temperature on the
      peptide stability were studied. The influence of various gamma sterilization
      doses, as well as the conditions under which the implants were irradiated, were
      also investigated. Peptide stability in the polymeric matrix was evaluated at
      various temperatures and at various time intervals up to 9 months.

PMID- 10205642
TI  - alpha-Chymotrypsin-catalyzed degradation of desmopressin (dDAVP): influence of
      pH, concentration and various cyclodextrins.
AB  - Desmopressin [1-(mercaptopropanoic acid)-8-D-arginine vasopressin; dDAVP] is a
      vasopressin analogue with a selective antidiuretic effect. The oral
      bioavailability of desmopressin is limited due both to its high hydrophilicity
      leading to a low intestinal permeability and to low enzymatic stability. The
      degradation of desmopressin was investigated in aqueous buffer solutions (pH 6.00
      9.00) containing the enzyme alpha-chymotrypsin at a concentration of 0.50 mg/ml
      at 37 degrees C. The degradation of desmopressin was also studied in solutions
      containing alpha-chymotrypsin in the concentration range 0.10-1.00 mg/ml (pH 7.40
      and 37 degrees C). The rate of degradation was shown to be highly dependent on
      both enzyme concentration and pH. Maximal alpha-chymotrypsin activity was
      observed in the pH range 7.40-8.00. It was observed that phenylalanine was formed
      during the degradation of desmopressin. Phenylalanine was formed in the amount of
      20% in 120 min. In the same time period 95% of desmopressin was degraded. The
      formation of phenylalanine can be explained from the substrate specificity of
      alpha-chymotrypsin. Cyclodextrins are known to stabilize drugs including peptides
      against both chemical and enzymatic degradation. In this study it was shown that
      hydroxypropyl cyclodextrins (alpha, beta and gamma) stabilized desmopressin
      against alpha-chymotrypsin-catalyzed degradation. The stabilization was by a
      factor of 3, 9 and 8 at the concentration 12.5% (w/v) for hydroxypropyl-alpha
      cyclodextrin, hydroxylpropyl-beta-cyclodextrin and hydroxypropyl-gamma
      cyclodextrin.

PMID- 10205643
TI  - Potential of low molecular mass chitosan as a DNA delivery system:
      biocompatibility, body distribution and ability to complex and protect DNA.
AB  - Cationic polymers have the potential for DNA complexation and it is recognised
      that they may be useful as non-viral vectors for gene delivery. Highly purified
      chitosan fractions of < 5000 Da (N1), 5000-10,000 Da (N2) and > 10,000 Daltons
      (N3) were prepared and characterised in respect of their cytotoxicity, ability to
      cause haemolysis, ability to complex DNA as well as to protect DNA from nuclease
      degradation. Also the biodistribution of 125I-labelled chitosans was followed at
      5 and 60 min after intravenous injection into male Wistar rats. All chitosan
      fractions displayed little cytotoxicity against CCRF-CEM and L132 cells (IC50 > 1
      mg/ml), and they were not haemolytic (< 15% lysis after 1 and 5 h). Chitosan-DNA
      interaction at a charge ration of 1:1 was much greater than seen for poly(L
      lysine) and complexation resulted in inhibition of DNA degradation by DNase II:
      99.9 +/- 0.1, 99.1 +/- 1.5 and 98.5 +/- 2.0% for N1, N2 and N3, respectively.
      After intravenous injection, all the chitosans showed rapid blood clearance, the
      plasma levels at 1 h being 32.2 +/- 10.5% of recovered dose for N1 and 2.6 +/-
      0.5% of recovered dose for N3. Liver accumulation was molecular mass dependent,
      being 26.5 +/- 4.9% of the recovered dose for N1 and 82.7 +/- 1.9% of the
      recovered dose for N3. The observations that the highly purified chitosan
      fractions used were neither toxic nor haemolytic, that they have the ability to
      complex DNA and protect against nuclease degradation and that low molecular
      weight chitosan can be administered intravenously without liver accumulation
      suggest there is potential to investigate further low molecular weight chitosans
      as components of a synthetic gene delivery system.

PMID- 10205644
TI  - Investigation on process parameters involved in preparation of poly-DL-lactide
      poly(ethylene glycol) microspheres containing Leptospira Interrogans antigens.
AB  - Block copolymer, poly-DL-lactide-poly(ethylene glycol) (PELA) with 11.5% of
      poly(ethylene glycol) (PEG) content was prepared by bulk ring-opening
      polymerization using stannous chloride as initiator. PELA microspheres with
      entrapped Leptospira Interrogans antigens, outer membrane protein (OMP) were
      elaborated by solvent extraction method based on the formation of multiple w/o/w
      emulsion, and the resulting microspheres were characterized with respect to
      particle size, OMP entrapment and morphology characteristics. The purpose of the
      present study is to perform the optimization of preparative parameters for OMP
      loaded PELA micropsheres to control particle size and improve the OMP
      encapsulation efficiency. Of all the parameters investigated, the polymer
      concentration of organic phase and the external aqueous phase volume play major
      roles on particle size, while the organic phase volume, internal aqueous phase
      volume and the addition of surfactant into the internal aqueous phase display
      considerable effects on OMP loading efficiency. A small volume of internal
      aqueous phase and intermediate volumes of organic phase and external aqueous
      phase were favorable to achieve micropsheres with a size of 1-2 microns and high
      antigen encapsulation efficiency (70-80%). In vitro OMP release profiles from
      PELA microspheres consist of a small burst release followed by a gradual release
      phase. The OMP release rate shows some relations with the porous and water
      swollen inner structure of the microspheres matrix. The presence of surfactant in
      microspheres accelerates OMP release, but the OMP entrapment within microspheres
      shows limited effects on the release profile.

PMID- 10205645
TI  - Development of 5-iodo-2'-deoxyuridine milling process to reduce initial burst
      release from PLGA microparticles.
AB  - The aim of this study was to prepare 5-iodo-2'-deoxyuridine (IdUrd) loaded
      poly(d,l-lactide-co-glycolide) (PLGA) microspheres with a reduced initial burst
      in the in vitro release profile, by modifying the drug grinding conditions. IdUrd
      particle size reduction has been performed using spray-drying or ball milling.
      Spray-drying significantly reduced drug particle size with a change of the
      initial crystalline form to an amorphous one and led to a high initial burst.
      Conversely, ball milling did not affect the initial IdUrd crystallinity.
      Therefore, the grinding process was optimized to emphasize the initial burst
      reduction. A first step allowed us to set qualitative parameters such as ball
      number (7) and cooling with liquid nitrogen to obtain a mean size reduction and a
      narrow distribution. In a second step, three parameters including milling speed,
      drug amount and time were studied by a response surface analysis. The
      interrelationship between drug amount and milling speed was the most significant
      factor. To reduce particle size it should be necessary to use a moderate speed
      associated with a sufficient drug amount (400-500 mg). IdUrd release from
      microparticles prepared by the o/w emulsion/extraction solvent evaporation
      process with the lowest crystalline particle size (15.3 microns) was studied.
      Burst effect could be reduced significantly. Concerning the first phase of drug
      release, the burst was 8.7% for 15.3 microns compared to 19% for 19.5 microns
      milled drug particles.

PMID- 10205646
TI  - [The oxidation resistance of heparin-precipitated blood serum beta-lipoproteins
      in ischemic heart disease].
AB  - Oxidative modification of low-density lipoproteins plays the key role in the
      pathogenesis of atherosclerosis. The purpose of this study was to assess
      oxidation resistance of serum beta-lipoproteins (beta-LP) in coronary patients in
      comparison with normal subjects by a simple method. The study was carried out in
      37 male patients with coronary disease and type IIb dyslipoproteinemia and 48
      healthy men with normolipidemia. beta-LP was isolated by precipitation in the
      presence of heparin. The initial level of lipid peroxides in them and their
      oxidation resistance during incubation in the presence of 50 microM cooper ions
      were assessed. The baseline content of lipid peroxides in beta-LP was two-fold
      increased and oxidation resistance two-fold decreased in coronary patients as
      against normal controls. Oxidation resistance of precipitated beta-LP in coronary
      patients and normal subjects was different.

PMID- 10205647
TI  - [The gas chromatographic analysis of the fatty acids in the expired air in
      ischemic heart dis].
AB  - Lipids of exhaled air condensate (EAC) and sweat are analyzed by gas
      chromatography in coronary patients with myocardial infarction complicated by
      lung edema. Changes of lipid fatty acid spectrum in EAC and sweat were uniform:
      the levels of linoleic and arachidonic acids were increased, which can aggravate
      the disease and lead to complications.

PMID- 10205648
TI  - [A skin test for stress].

PMID- 10205649
TI  - [The cytological diagnosis of formations made up of elements of the peripheral
      nerves and their membranes based on the material from transthoracic punctures].

PMID- 10205650
TI  - [Morphological changes in the epithelial cell nuclei in chlamydial urethritis in
      men and the methods for optimizing the light-optical study of impression smears].

PMID- 10205651
TI  - [THe use of a biotin-labelled DNA probe for detecting the causative agents of
      chronic urogenital infections].
AB  - DNA hybridization for detecting HSV, CMV, C. trachomatis, and U. urealyticum by
      biotin-labeled DNA probe was used for investigating clinical specimens from
      patients with infertility and chronic urogenital inflammations. High sensitivity
      and specificity of the method was confirmed by the results of PCR, ELISA, and
      immunofluorescent methods in 80-90% cases. DNA hybridization technique is a
      simple method requiring no sophisticated equipment, which recommends it for the
      diagnosis of sexually-transmitted diseases at clinical laboratories.

PMID- 10205652
TI  - [A syphilis marker study of blood component donors].
AB  - Laboratory testing of donor blood is the key point in prevention of
      hemotransmissive syphilis. The probability of using diagnostic EIA kit
      RecombiBest antipallidum-strip (AO Vektor-Best, Novosibirsk) is assessed. Ninety
      two donor sera were tested. For assessing the sensitivity of the test system, 11
      sera of syphilis patients were titrated by double dilutions 1:10 to 1:1280 for
      each strip. In parallel with this, antibodies to T. pallidum were assessed in the
      precipitation microtest. EIA proved to be not only highly specific, but more
      sensitive than precipitation microtest. Antibodies to T. pallidum are detected by
      EIA in serum dilutions at least two times higher than the minimal titers in the
      precipitation test. Thus, the above diagnostic kit is recommended for screening
      of donors of blood and its components.

PMID- 10205653
TI  - [The isolation and quantitative estimation of motile enterococci].

PMID- 10205654
TI  - [The detection of cytomegalovirus DNA by the polymerase chain reaction in
      different biological materials in patients with organ allografts].
AB  - Ninety-eight patients with organ allografts were examined using the polymerase
      chain reaction (PCR). Cytomegalovirus (CMV) DNA was not found in the blood of any
      of 67 blood donors. At least 85% patients with CMV DNA in the plasma developed
      CMV disease. CMV DNA was detected in leukocytes of 22 (40.7%) out of 54 patients
      with negative results of analysis for CMV DNA in the plasma; 16 (29.6%) of these
      22 presented with clinical symptoms of CMV infection by the moment of
      investigation. Results of PCR analysis of blood, urine, and saliva specimens of
      30 patients examined did not always coincide. DNA isolated from the urine can
      contain components inhibiting DNA polymerase. Blood leukocytes or whole blood are
      the most suitable for the diagnosis of active and symptomatic CMV-infection.

PMID- 10205655
TI  - [The cytokines of the immune system: their basic properties and immunobiological
      activity (a lecture)].

PMID- 10205656
TI  - [Differential diagnosis using artificial neuronal networks].
AB  - In order to rule out the effects of subjective factors and decrease the number of
      diagnostic errors, artificial neuron nets are proposed. By means of these nets
      the subjective and half-empirical heuristics are replaced with rational
      diagnostic information based on quantitative and logic analysis. The proposed
      method was used for deriving the decisive regularities ensuring the differential
      diagnosis between infective endocarditis and active rheumatic fever, infective
      endocarditis and systemic lupus erythematosus, and systemic lupus erythematosus
      and active rheumatic fever. Reliability of diagnostic tables representing the
      decisive regularities in the usual form is confirmed by clinical data.

PMID- 10205657
TI  - [A computer program for intralaboratory quality control Qcontrol, version 1.0].

PMID- 10205658
TI  - [External quality control of the laboratory determination of glucose in the urine
      and material for its realization].
AB  - Urine of diabetics without concomitant diseases with a certain concentration of
      glucose was collected for preparing reference material. Water saturated with
      phenol (872 mmole/liter) was added to urine pool during intensive stirring on a
      magnetic stirrer at 20 degrees C, so that the final concentration of phenol were
      50 mmole/liter. Glucose content in the resultant reference material remained
      stable for 130 days at 18-20 degrees C. For glucose measurements, 2 ml reference
      material and 0.5 ml 2.5 M sodium oxide hydrate are put in centrifuge tubes,
      stirred, put on boiling water bath for 2 min, cooled, and colorimetried in
      cuvettes with 1-mm optic route. The content of monosaccharide is calculated using
      the proportion rule in comparison with the values for 139 mM reference glucose
      solution in control urine.

PMID- 10205660
TI  - Monoclonal antibodies against vascular endothelial growth factor 165 (VEGF165):
      neutralization of biological activity and recognition of the epitope.
AB  - Five antibodies against vascular endothelial growth factor 165 (VEGF165) were
      obtained. These antibodies, Ab-2, Ab-20, Ab-153, Ab-309, Ab-342, were able to
      recognize not only native VEGF165, but also reducing VEGF165. Three of the
      antibodies, Ab-153, Ab-309, Ab-342, were identified as VEGF165 neutralizing
      antibody on the basis of its ability to inhibit the proliferation of human
      umbilical vein endothelial cells (HUVEC) induced by VEGF165 and the binding of
      [125I]-VEGF165 to receptors on HUVEC. The fragments of E1 (VEGF120-135) and E2
      (VEGF46-60) recognized by neutralizing antibodies may be related the receptor
      binding domain of VEGF.

PMID- 10205661
TI  - Cloning of a tellurite resistance determinant from Bacillus stearothermophilus V
      in Escherichia coli.
AB  - A potassium tellurite-resistance determinant was isolated from Bacillus
      stearothermophilus V and cloned in Escherichia coli. Transformed cells formed
      black colonies when grown on solid media containing permissive tellurite
      concentrations. The resistance determinant was contained in a B.
      stearothermophilus V chromosomal DNA fragment of 7 kb.

PMID- 10205662
TI  - Human milk lactoferrin binds ATP and dissociates into monomers.
AB  - The physiological role of lactoferrin (LF) is still unclear, but it has been
      suggested to be responsible for primary defence against microbial infections.
      Many different unique functions have been attributed to LF, including DNA and RNA
      binding, and transport into the nucleus, where LF binds to specific DNA sequences
      and activates transcription. Here we present evidence that in addition to the
      above (and below) mentioned functions LF binds ATP with a stoichiometry of 1 mole
      of nucleotide per mole of the protein and a Kd = 0.3 mM. The ATP-binding site is
      localized in the C-terminal domain of LF, in contrast to the antibacterial and
      polyanion-binding sites, which are located in the N-terminal domain. Binding of
      ATP by LF leads to dissociation of its oligomeric forms and to a change of the
      protein's interaction with polysaccharides, DNA and proteins.

PMID- 10205663
TI  - Purification and characterization of trichomaglin--a novel ribosome-inactivating
      protein with abortifacient activity.
AB  - Trichomaglin, a novel ribosome-inactivating protein, has been isolated from root
      tuber of a plant Maganlin (Trichosanthes Lepiniate, Cucurbitaceae). The isolation
      and purification procedure included ammonium sulfate precipitation, Sephadex G-75
      chromatography and CM-Sephadex C-50 chromatography. The protein was identified to
      be homogeneous by SDS-PAGE and FPLC analysis. Its molecular weight is 24,673
      dalton and isoelectric point is 5.8, determined by electrospray ionization mass
      spectroscopy and isoelectric focusing gel electrophoresis respectively.
      Trichomaglin can inhibit protein synthesis in rabbit reticulocyte lysate with
      ID50 of 10.1 nM. When rat ribosome was incubated with trichomaglin, a diagnostic
      RNA fragment appeared on polyacrylamide gel after ribosomal RNAs were treated
      with acidic aniline. It was concluded that trichomaglin is an RNA N-glycosidase.
      In addition, it has been verified to be an abortifacient protein.

PMID- 10205664
TI  - Effects of chronic electroconvulsive shock on the expression of beta-adrenergic
      receptors in rat brain: immunological study.
AB  - The purpose of the present study is to determine the effect of chronic
      electroconvulsive shock (ECS) on the expression of beta-adrenergic receptors in
      rat brain by Western blot using mAb beta CO2, a monoclonal antibody against beta
      adrenergic receptors. Rats in ECS treated groups received maximal ECS (70 mA, 0.5
      second, 60 Hz) through ear-clip electrodes for 12 consecutive days. The
      experiment was carried out in 14 discrete regions of brain. Chronic ECS reduced
      the expression of beta-adrenergic receptors in frontal cortex, temporal cortex,
      parietooccipital cortex, hippocampus and limbic forebrain, but not in other areas
      of brain. The regional specificity and the magnitude of the reduction of receptor
      expression are well correlated with those of the reduction of receptor ligand
      binding, which was determined using [3H]dihydroalprenolol. To the best of our
      knowledge, this is the first report to demonstrate that chronic ECS decreases the
      expression of receptor protein in specific regions of rat brain.

PMID- 10205665
TI  - Transcriptional regulation of the CDK inhibitor p16INK4a gene by a novel pRb
      associated repressor, RBAR1.
AB  - p16, also known as INK4a, CDKN2, or MTS1, plays an important role in the control
      of the cell cycle progression, and retinoblastoma protein (pRb) is suggested to
      be involved in the transcriptional regulation of p16. However, it is not fully
      understood how pRb regulates transcription of the p16 gene. Nuclear proteins
      prepared only from the pRb-nonfunctional human tumor cells were found to bind to
      the 5'-flanking sequence of the p16 gene in the presence of Zn2+ by
      electrophoretic mobility shift assay (EMSA). EMSA using mutagenized 5'-flanking
      sequences as competitors suggested that the sequence at position -97 to -87
      relative to first ATG of the p16 gene was critical for protein binding. Transient
      reporter assay indicated that the sequence identified by EMSA acted as a silencer
      element in the pRb-nonfunctional tumor cells, showing the presence of a
      transcriptional repressor associated with functional pRb (RBAR1).

PMID- 10205666
TI  - Cloning, sequence analysis and expression in E. coli of the cDNA of the thrombin
      like enzyme (pallabin) from the venom of Agkistrodon halys pallas.
AB  - The cDNA of the thrombin-like enzyme (pallabin) from the venom of Agkistrodon
      halys pallas was cloned and sequenced. The length of the cDNA is 923bp which
      includes 120bp of noncoding region and 780bp of coding region. Pallabin was
      synthesized as a prozymogen with 260 amino acids, which includes a signal peptide
      of 18 amino acids, a proposed propeptide of 6 amino acids and a matured peptide
      of 236 amino acids. Pallabin exhibits a strong amino acid similarity to the
      serine proteases isolated from other snake venoms. It contains 12 cysteins which
      form 6 disulfide bridges. Like other serine proteases, it also has three
      conserved catalytically active sites: His41, Asp86 and Ser182. To our knowledge,
      this study is the first report concerning the cDNA of a thrombin-like enzyme from
      Agkistrodon halys pallas. The cDNA was cloned into the expression plasmid pT7ZZa
      and expressed in E.coli. The recombinant pallabin immunologically reacted with
      its specific antibody.

PMID- 10205667
TI  - Effects of sulfhydryl compounds on the inhibition of erythrocyte membrane Na+(
      )K+ ATPase by ozone.
AB  - Exposure of human erythrocyte membranes to ozone (5 mumol/10 min) resulted in the
      inhibition of erythrocyte membrane Na+(-)K+ ATPase (EC.3.6.1.39). It was
      determined that, the degree of enzyme inhibition in the directly ozone exposed
      membranes was greater than that of membranes obtained from ozone exposed intact
      erythrocytes. In the presence of varying concentrations (0-1.0 mM) of
      dithiotrethiol or mercaptoethanol Na+(-)K+ ATPase activities of both types of
      ozone exposed membranes were increased almost proportionally with the
      concentration of dithiotrethiol or mercaptoethanol however, the activities were
      still lower than the normal Na+(-)K+ ATPase value. The results indicate that,
      dithiotrethiol or mercaptoethanol prevent the enzyme inhibition by ozone in
      vitro. This suggests that the membrane thiol groups are primary targets for ozone
      and thereby preventing the oxidation of essential functional groups of enzyme
      protein.

PMID- 10205668
TI  - CYP2B2 gene expression and phenobarbital induction in kidneys using an in vitro
      transcription system.
AB  - The induction of cytochrome P450 2B1 and 2B2 in rat liver in response to
      phenobarbital is mediated at the transcriptional level. While in extrahepatic
      tissue such as the kidney, the transcription level of the CYP 2B2 gene is much
      lower than in the liver. The transcriptional activity of the CYP2B2 promoter
      constructs in nuclear proteins from kidney revealed that the in vitro system
      maintained the tissue-specificity of CYP2B2 transcriptional induction but not
      that of the basal transcription of the gene.

PMID- 10205669
TI  - Roles of nitrate, nitrite and ammonium ion in phytochrome regulation of nitrate
      reductase gene expression in maize.
AB  - The influence of nitrate and its metabolites on the nitrate reductase (NR) gene
      expression and its relationship with phytochrome (Pfr) regulation of NR in
      etiolated maize leaves is examined. Nitrate induction and Pfr stimulation are
      brought about by independent signalling phenomena. Phorbol myristate acetate
      (PMA), a stimulator of protein kinase C (PKC), mimicked the effect of red light
      but could not replace the nitrate requirement for the induction of NR transcript
      accumulation. This suggests that while PKC-type enzymes may be involved in
      mediating the Pfr signal, nitrate may follow an independent signalling mechanism.
      Experiments with 5-hydroxytryptamine (5HT) and lithium ions (Li+), which are
      known to modulate phosphoinositide (PI) turnover, indicated that in addition to
      generating Pfr-induced second messengers for PKC activation, PI cycle may also
      generate other signals which mediate nitrate induction of NR gene expression in
      the dark. The products of nitrate reduction i.e., nitrite and ammonium ion had
      inhibitory and stimulatory effects respectively, on NR transcript accumulation.
      They work mainly at the level of nitrate induction.

PMID- 10205670
TI  - Aldosterone directly induces Na, K-ATPase alpha 1-subunit mRNA in the renal
      cortex of rat.
AB  - The change of blood pressure and the induction of Na, K-ATPase alpha 1-subunit
      mRNA have been investigated in the renal cortex of aldosterone-treated
      hypertensive rat. The increase of blood pressure by aldosterone-treatment for 25
      days was decreased by the treatment of amiloride or spironolactone. The level of
      Na, K-ATPase alpha 1-subunit mRNA of the renal cortex in aldosterone-treated rat
      was increased than that in the control, and its increase was repressed by
      treatment of spironolactone, but not altered by the treatment of amiloride. This
      result suggests that the increase of Na, K-ATPase alpha 1-subunit mRNA in the
      renal cortex of aldosterone-treated hypertensive rat may be related with the
      direct induction of Na, K-ATPase mRNA without the increase of Na-traffic through
      Na-channel.

PMID- 10205671
TI  - Purification of cytochrome P-450 from pig testis by aniline-sepharose 4B and
      isoelectric focusing.
AB  - Testicular cytochrome P-450 was purified by a procedure including preparative
      isoelectrofocusing. The cytochrome P-450 was determined to have an isoelectric
      point of 6.47 on analytical isoelectric focusing. The purified cytochrome P-450
      was found to be homogeneous and its molecular weight was estimated to be 52,000
      on polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate.
      The carbon monoxide difference spectrum with a peak at 448 nm exhibited
      absorption spectrum of a typical cytochrome P-450. 284-fold purification was
      achieved with an yield of 10.6%. Following preparation of the microsomes, the
      purification is accomplished by a two-step procedure utilizing Aniline-Sepharose
      4B column chromatography and preparative isoelectric focusing.

PMID- 10205672
TI  - High level expression of soluble angiogenin in Escherichia coli.
AB  - Human angiogenin was genetically engineered and contained the E. coli Omp A
      signal sequence for secreting soluble angiogenin to the periplasm under tac
      promoter control. The angiogenin sequence was encoded in a single gene and
      expressed as a 14.4 kilodalton soluble protein in E. coli. It was purified by CM
      Sepharose ion-exchange chromatography and by a heparin-Sepharose affinity
      chromatography procedure. The biological activity of angiogenin was established
      by its ability to inhibit mRNA-dependent rabbit reticulocyte cell-free
      translation.

PMID- 10205673
TI  - Cloning and expression of bovine herpesvirus-1 glycoprotein C.
AB  - Glycoprotein C (gC) of Bovine Herpesvirus-1 (BHV-1) is expressed at high levels
      on surface of infected cells and on virus envelope. It is relatively
      immunodominant in antibody response to BHV-1 infection and protective in
      immunized bovines against BHV-1 challenge. In an attempt to express gC in
      mammalian cells, the 2.4 kb BamHI-EcoRI fragment, containing complete coding
      sequence of the gC gene was excised from a recombinant plasmid and cloned under
      the control of RSV-LTR. The resultant plasmid pRSV-gC was transfected into MDBK
      cells and expression of gC was detected by indirect immunofluorescence. The non
      permeabilized cells revealed surface expression of gC.

PMID- 10205674
TI  - Lysosomal glycerophosphocholine phosphodiesterase in Tetrahymena.
AB  - The purification and characterization of a novel phosphodiesterase (PDE) is
      presented. The activity was detected in the extracellular medium of Tetrahymena
      thermophila cultures, by the release of p-nitrophenol from p
      nitrophenylphosphocholine (PNPPC) with an acidic pH optimum. In cell homogenates,
      it is sedimentable, shows a latency similar to that of acid phosphatase and is co
      secreted with this enzyme, indicating that it is a lysosomal hydrolase. PNPPC-PDE
      was purified to homogeneity from the extracellular medium, yielding a single band
      of 58 kD on SDS polyacrylamide gel electrophoresis. It catalyzed the release of
      glycerol from glycerophosphocholine (GPC) and GPC competitively inhibits
      degradation of PNPPC. We present further evidence indicating that the natural
      substrate for PNPPC-PDE is GPC. Thus, Tetrahymena becomes the first eukaryote in
      which a lysosomal GPC-PDE is observed. This finding provides a new pathway for
      the complete breakdown of phosphatidylcholine in a lysosomal medium.

PMID- 10205675
TI  - Effect of dietary fish oil on tumor-induced hyperlipidemia and tumor growth in
      rats implanted with a methylcholanthrene-induced sarcoma.
AB  - Male Fischer 344 rats implanted with a methylcholanthrene-induced sarcoma (MCS),
      along with normal (or control) animals, were fed diets containing either 10% com
      oil (CO) or 2% CO + 8% fish oil (FO), designated as diets CO and FO,
      respectively, in a study designed to determine the effect of dietary FO on serum
      lipids (in the presence or absence of a tumor) and the growth and fatty acid
      composition of the MCS. For both diets, MCS-bearing rats had significantly (p <
      0.05) higher serum levels of triglycerides, cholesterol, phospholipids, and total
      lipids than controls. For both controls and tumor-bearers, serum levels of all
      these lipids were, with the exception of cholesterol for the tumorbearers,
      significantly lower in rats receiving the FO diet than for the corresponding
      groups receiving the CO diet. Relative to rats fed the CO diet, those fed the FO
      diet had significantly higher serum levels of some fatty acids (e.g., 20:5n-3)
      but significantly lower levels of others (e.g., 18:2n-6), regardless of tumor
      status. For the tumor-bearers, differences in the levels of fatty acids in MCS
      tissue reflected differences in the fatty acid composition of total serum lipids.
      Sarcoma growth was unaffected by diet. Thus, feeding dietary FO resulted in
      changes in the lipid status of both control and tumor-bearing rats. Since sarcoma
      growth was unaffected by diet, the reduction in the severity of MCS-induced
      hyperlipidemia by FO appears to be due to an effect of the oil per se.

PMID- 10205676
TI  - Hepatitis B virus: DNA polymerase activity of deletion mutants.
AB  - The hepadnavirus P gene product is a multifunctional protein with priming, DNA-
      and RNA-dependent DNA polymerase, and RNase H activities. Nested N- or C-terminal
      deletion mutations and deletions of domain(s) in human HBV polymerase have been
      made. Wild-type and deletion forms of MBP-fused HBV polymerase were expressed in
      E. coli, purified by amylose column chromatography, and the DNA-dependent DNA
      polymerase activities of the purified proteins were compared. Deletion of the
      terminal protein or spacer regions reduced enzyme activity to 70%, respectively.
      However, deletion of the RNase H domain affected polymerase activity more than
      that of the terminal protein or spacer region. The polymerase domain alone or the
      N-terminal deletion of the polymerase domain still exhibited enzymatic activity.
      In this report, it is demonstrated that the minimal domain for the polymerizing
      activity of the HBV polymerase is smaller than the polymerase domain.

PMID- 10205677
TI  - Cloning and functional expression of rAOP9L a new member of aquaporin family from
      rat liver.
AB  - A new aquaporin was isolated from rat liver based on homology to known
      aquaporins. A 1408 bp cDNA was sequenced (designated rAQP9L) with a 885 bp open
      reading frame encoding a 295 amino acid hydrophobic protein. rAQP9L has the
      greatest amino-acid sequence identity with human AQP9 (75%) and a less homology
      with AQP3 (49%) and AQP7 (47%). Northern blot analysis indicated a 1.4-kb
      transcript expressed strongly in liver > testis > brain = lung. Expression of
      rAQP9L cRNA in Xenopus oocytes increased osmotic water permeability by 6-folds
      which was inhibited by 0.3 mM mercury chloride by 42%. rAQP9L also facilitated
      glycerol and urea transport by 2- and 5-folds, respectively. The large
      discrepancy of tissue distribution between hAQP9 and rAQP9L suggest that rAQP9L
      is a new aquaporin, which is involved in transport of urea as well as water in
      liver.

PMID- 10205678
TI  - Sedimentation analysis of muscle glycogen phosphorylase b entrapped in hydrated
      reversed micelles of aerosol OT in octane.
AB  - The oligomeric state and formation of supramolecular structures of glycogen
      phosphorylase b from rabbit skeletal muscles have been studied in the system of
      hydrated reversed micelles of aerosol OT (AOT) in octane. Sedimentation studies
      show that the oligomeric state of the enzyme is controlled by the degree of
      hydration of micelles. Monomeric, dimeric, trimeric, tetrameric, hexameric, or
      octameric forms of the enzyme were observed depending on the degree of micelle
      hydration.

PMID- 10205679
TI  - Optical biosensor studies on the productive complex formation between the
      components of cytochrome P450scc dependent monooxygenase system.
AB  - The formation of individual complexes between the components of cholesterol side
      chain cleavage system-cytochrome P450scc, adrenodoxin (Ad) and adrenodoxin
      reductase (AdR) was kinetically characterized and their association and
      dissociation rate constants were measured by optical biosensor. The dominant role
      of interprotein electrostatic interactions in productive complex formation was
      demonstrated. Despite of the fact that P450scc and AdR complete for the binding
      with the same or closely placed negatively charged groups on the surface of
      immobilized Ad, the formation of the AdR/P450scc/Ad ternary complex upon AdR
      immobilization on dextran was registered. It is shown, that Ad does not bind to
      AdR immobilized via amino groups AdRim but it is possible only after the
      preliminary binding of P450scc to AdRim. The life time of such ternary complex,
      about 15 s, is sufficient for the realization of 5-8 catalytic cycles.

PMID- 10205681
TI  - No secrets any more: the erosion of confidentiality.

PMID- 10205680
TI  - Cellular uptake and delivery monitoring of liposome/DNA complexes during in vitro
      transfection of CFTR gene.
AB  - The cellular uptake and distribution of cationic liposomes Dc-Chol/DOPECFTR gene
      complexes were assessed by electronic and confocal laser scanner microscopy
      (CLSM) for the CFTR gene transfer to human adenocarcinoma and tracheal epithelial
      cell lines. Cationic lipid forms unilamellar and multilamellar vesicles capable
      of rapid and efficient transport of gene into target cells. The number of
      fluorescent complexes was increasing with time in cells up to 6 hours showing a
      punctate and homogeneous DNA distribution in the cytoplasmatic and nuclear
      compartments, including the nucleolus. No significant difference in the
      biochemical and cellular behavior was observed between the investigated system
      and other systems previously tested. This study adds new insights into the CFTR
      cationic liposome-mediated gene delivery.

PMID- 10205682
TI  - The Intercollegiate Academic Board of Sport and Exercise Medicine.

PMID- 10205683
TI  - "Boosting" performance in disability sport.

PMID- 10205684
TI  - Time to get tough on doping!

PMID- 10205685
TI  - Women's greatest handicaps: sex, medicine, and men.

PMID- 10205686
TI  - Exercise and sport in cystic fibrosis: benefits and risks.

PMID- 10205687
TI  - Exercise in cardiac rehabilitation.

PMID- 10205688
TI  - Accumulation of physical activity for health gains: what is the evidence?

PMID- 10205689
TI  - Echocardiographic examination of cardiac structure and function in elite cross
      trained male and female Alpine skiers.
AB  - OBJECTIVE: To assess cardiac structure and function in elite cross-trained male
      and female athletes (Alpine skiers). METHODS: Sixteen athletes (10 male, six
      female) and 19 healthy sedentary control subjects (12 male, seven female)
      volunteered to take part in the study. Basic anthropometry determined height,
      body mass, body surface area, and fat free mass. Cardiac dimensions and function
      were determined by two dimensional, M mode, and Doppler echocardiography.
      Absolute data and data corrected for body size (allometrically determined) were
      compared by two way analysis of variance and post hoc Scheffe tests. RESULTS:
      Absolute left ventricular internal dimension in diastole (LVIDd), septal and
      posterior wall thickness and left ventricular mass were larger in athletes than
      controls (p < 0.05) and also increased in the men (p < 0.05) compared with women
      (except for septal thickness in controls). An increased LVIDd, septal thickness,
      posterior wall thickness, and left ventricular mass in athletes persisted after
      correction for body size except when LVIDd was scaled by fat free mass. Cardiac
      dimensions did not differ between the sexes after correction for body size. All
      functional indices were similar between groups. CONCLUSION: There is evidence of
      both left ventricular chamber dilatation and wall enlargement in cross trained
      athletes compared with controls. Differences in absolute cardiac dimensions
      between the sexes were primarily due to greater body dimensions in the men.

PMID- 10205691
TI  - Incidence and causes of tenosynovitis of the wrist extensors in long distance
      paddle canoeists.
AB  - OBJECTIVES: To investigate the incidence and causes of acute tenosynovitis of the
      forearm of long distance canoeists. METHOD: A systematic sample of canoeists
      competing in four canoe marathons were interviewed. The interview included
      questions about the presence and severity of pain in the forearm and average
      training distances. Features of the paddles and canoes were determined. RESULTS:
      An average of 23% of the competitors in each race developed this condition. The
      incidence was significantly higher in the dominant than the nondominant hand but
      was unrelated to the type of canoe and the angle of the paddle blades. Canoeists
      who covered more than 100 km a week for eight weeks preceding the race had a
      significantly lower incidence of tenosynovitis than those who trained less.
      Environmental conditions during racing, including fast flowing water, high winds,
      and choppy waters, and the paddling techniques, especially hyperextension of the
      wrist during the pushing phase of the stroke, were both related to the incidence
      of tenosynovitis. CONCLUSION: Tenosynovitis is a common injury in long distance
      canoeists. The study suggests that development of tenosynovitis is not related to
      the equipment used, but is probably caused by difficult paddling conditions, in
      particular uneven surface conditions, which may cause an altered paddling style.
      However, a number of factors can affect canoeing style. Level of fitness and the
      ability to balance even a less stable canoe, thereby maintaining optimum paddling
      style without repeated eccentric loading of the forearm tendons to limit
      hyperextension of the wrist, would seem to be important.

PMID- 10205690
TI  - Reduction of exercise-induced asthma in children by short, repeated warm ups.
AB  - AIM: To study the effect of a warm up schedule on exercise-induced asthma in
      asthmatic children to enable them to engage in asthmogenic activities. METHOD: In
      the first study, peak flows during and after three short, repeated warm up
      schedules (SRWU 1, 2, and 3), identical in form but differing in intensity, were
      compared in 16 asthmatic children. In the second study the efficiency of the best
      of these SRWU schedules was tested on 30 young asthmatic children. Children
      performed on different days a 7 minute run alone (EX1) or the same run after an
      SRWU (EX2). RESULTS: The second study showed that for most children (24/30) the
      fall in peak flow after EX2 was less than that after EX1. The percentage fall in
      peak flow after EX2 was significantly correlated with the percentage change in
      peak flow induced by SRWU2 (r = 0.68). The children were divided into three
      subgroups according to the change in peak flow after SRWU2: (G1: increase in peak
      flow; G2: < 15% fall in peak flow; G3: > 15% fall in peak flow). Only the
      children in the G3 subgroup did not show any gain in peak flow after EX2 compared
      with EX1. CONCLUSION: The alteration in peak flow at the end of the SRWU period
      was a good predictor of the occurrence of bronchoconstriction after EX2. An SRWU
      reduced the decrease in peak flow for most of the children (24/30) in this
      series, thus reducing subsequent post-exercise deep bronchoconstriction.

PMID- 10205692
TI  - Injuries caused by falling soccer goalposts in Denmark.
AB  - OBJECTIVE: A falling soccer goalpost is associated with the potential risk of
      serious injury that can sometimes even be fatal. The aim of the study was to
      analyse the extent of the problem in Denmark and focus on the mechanism of injury
      and prevention. METHODS: Data were analysed for the period 1989-1997 from the
      European Home and Leisure Accident Surveillance System, which is an electronic
      register of the injuries seen in the casualty departments of the hospitals of
      five selected cities in Denmark representing 14% of the Danish population; in
      addition, fatal accidents in the whole of Denmark since 1981 were examined. Forty
      two injured persons were interviewed about the circumstances of the accident.
      Attempts were made to estimate the proportion of goalposts secured by
      counterweight in the five different regions, compared with the proportion secured
      with ground stakes and those that were unsecured, by analysing data from the
      largest producers of goalposts in Denmark. RESULTS: In the period 1981-1988, two
      fatal accidents were recorded. In the period 1989-1997, 117 people were injured
      by a falling goalpost; six of the injuries required hospitalisation. Some 88% of
      the injured were under the age of 15. In a telephone interview with 42 of the
      injured, 50% stated that the goalpost fell because someone was hanging on the
      crossbar. Comparing the five different regions with respect to the proportion of
      goalposts secured by counterweight and the number of accidents, the following
      relation was found. Areas in which a high percentage of the goalposts were
      secured by a counterweight correlated inversely with a high number of accidents
      (r = -0.9; p = 0.04). CONCLUSION: Soccer is a widely played sport and it is
      important to be aware that accidents caused by falling goalposts can occur and
      that they presumably can be prevented by proper use of goalposts, by using secure
      goalposts, and by securing old goalposts with a counterweight.

PMID- 10205693
TI  - Velocity associated characteristics of force production in college weight
      lifters.
AB  - OBJECTIVE: To determine velocity specific isokinetic forces and cross sectional
      areas of reciprocal muscle groups in Olympic weight lifters. METHODS: The cross
      sectional area of the flexor or extensor muscles of the elbow or knee joint was
      determined by a B-mode ultrasonic apparatus in 34 college weight lifters and 31
      untrained male subjects matched for age. Maximum voluntary force produced in the
      flexion and extension of the elbow and knee joints was measured on an isokinetic
      dynamometer at 60, 180, and 300 degrees/s. RESULTS: The average cross sectional
      area was 31-65% higher, and the force was 19-62% higher in weight lifters than in
      the untrained subjects. The ratio of force to cross sectional area was the same
      in both groups. The weight lifters showed a lower velocity associated decline in
      force than untrained subjects in the elbow and knee flexors but not in the
      extensors. CONCLUSIONS: These results indicate that for muscle contractions with
      velocities between 60 degrees/s and 300 degrees/s the difference in isokinetic
      force between weight lifters and untrained subjects can be primarily attributed
      to the difference in the muscle cross sectional area. However, the lower velocity
      associated decline in force implies that weight lifters may have a higher force
      per cross sectional area than untrained subjects at velocities above 300
      degrees/s.

PMID- 10205694
TI  - Dynamic strength of the quadriceps muscle and sports activity.
AB  - The study objectives were to examine the dynamic strength of the quadriceps
      muscle in athletes, and investigate its association with participation in sport.
      The study comprised 168 active competitive non-pregnant athletes, aged 14-24
      years. The dynamic strength of their quadriceps muscle was measured, and they
      answered a questionnaire about sports activity and occupation. The dynamic
      strength of the quadriceps muscle was significantly higher in men than in women,
      and was positively associated with body weight, years of jogging, years of
      soccer, and weekly hours of basketball. In conclusion, the dynamic strength of
      the quadriceps muscle seems to be associated with sports activity. The results
      suggest sport specific adaptation, which may reflect high levels of running and
      jumping activity.

PMID- 10205695
TI  - Effects of physical and sporting activities on balance control in elderly people.
AB  - OBJECTIVE: Balance disorders increase with aging and raise the risk of accidental
      falls in the elderly. It has been suggested that the practice of physical and
      sporting activities (PSA) efficiently counteracts these age related disorders,
      reducing the risk of falling significantly. METHODS: This study, principally
      based on a period during which the subjects were engaged in PSA, included 65
      healthy subjects, aged over 60, who were living at home. Three series of
      posturographic tests (static, dynamic with a single and fast upward tilt, and
      dynamic with slow sinusoidal oscillations) analysing the centre of foot pressure
      displacements or electromyographic responses were conducted to determine the
      effects of PSA practice on balance control. RESULTS: The major variables of
      postural control were best in subjects who had always practised PSA (AA group).
      Those who did not take part in PSA at all (II group) had the worst postural
      performances, whatever the test. Subjects having lately begun PSA practice (IA
      group) had good postural performances, close to those of the AA group, whereas
      the subjects who had stopped the practice of PSA at an early age (AI group) did
      not perform as well. Overall, the postural control in the group studied decreased
      in the order AA > IA > AI > II. CONCLUSIONS: The period during which PSA are
      practised seems to be of major importance, having a positive bearing on postural
      control. It seems that recent periods of practice have greater beneficial effects
      on the subject's postural stability than PSA practice only at an early age. These
      data are compatible with the fact that PSA are extremely useful for elderly
      people even if it has not been a lifelong habit.

PMID- 10205696
TI  - Effect on nasal resistance of an external nasal splint and isotonic exercise.
AB  - OBJECTIVES: The now commonplace wearing of external nasal splints by sportsmen
      and athletes has never been scientifically evaluated. The present study looks
      into the effect of isotonic exercise on nasal resistance, and examines whether
      this effect is altered by the wearing of an external nasal splint. METHODS:
      Twenty subjects not suffering from rhinitis were tested. Nasal resistance
      measurements were recorded using an anterior rhinomanometer before and after
      isotonic exercise with and without an external nasal splint. Pulse and blood
      pressure were measured before and after exercise. RESULTS: Significant changes
      were observed in pulse (p < 0.001) and both systolic (p < 0.002) and diastolic (p
      < 0.001) blood pressure in response to exercise. Significant differences were
      seen in nasal resistance when the splint was applied (p < 0.001) and after
      exercise (p < 0.003). No significant difference was observed after exercise when
      the splint was worn (p = 0.167). CONCLUSIONS: External nasal splints decrease
      nasal resistance at rest but are of little value during isotonic exercise.

PMID- 10205697
TI  - Sonographic incidence of tendon microtears in athletes with chronic Achilles
      tendinosis.
AB  - OBJECTIVE: To assess the number and distribution of tendon microtears in
      asymptomatic controls and athletes with chronic Achilles tendinitis or partial
      thickness tears using high resolution ultrasound. METHODS: The mean number of
      microtears in three random tendon cross sections were recorded per tendon third
      in 19 asymptomatic volunteers, 16 athletes with symptomatic chronic Achilles
      tendinitis, and eight athletes with partial Achilles tendon rupture. RESULTS:
      Microtears were most numerous in the middle third section of the Achilles tendon.
      Some 67% of tendons in the control group had no microtears, and 28% showed a
      single microtear. Only 18% of the athletes with chronic Achilles tendinitis and
      none of the athletes with partial tendon rupture were without microtears in the
      middle third of their Achilles tendon. Of the tendons with chronic tendinitis,
      13% had more than three microtears per section which increased to 87% in tendons
      exhibiting partial rupture. CONCLUSIONS: There appears to be an association
      between microtear formation and Achilles tendon rupture.

PMID- 10205698
TI  - Injury to the first rib synchondrosis in a rugby footballer.
AB  - Injuries to the first rib synchondrosis are uncommon in sport. The potential for
      serious complications following posterior displacement is similar to that seen
      with posterior sternoclavicular joint dislocation. Clinical examination and plain
      radiography may not provide a definitive diagnosis. Computerised tomography is
      the most appropriate imaging modality if this injury is suspected. Posterior
      dislocation of the first rib costal cartilage with an associated fracture of the
      posterior sternal aspect of the synchondrosis has not been previously reported.

PMID- 10205699
TI  - Simultaneous bilateral elbow dislocation in an international gymnast.
AB  - Elbow dislocation is a rare injury in elite athletes. We report an unusual case
      of simultaneous bilateral elbow dislocations with a unilateral radial head
      fracture in an international female athlete competing on the asymmetrical bars.
      These injuries require prompt reduction and immediate mobilisation if an abrupt
      end to a promising career is to be prevented.

PMID- 10205700
TI  - Safe relief of rest pain that eases with activity in achillodynia by intrabursal
      or peritendinous steroid injection: the rupture rate was not increased by these
      steroid injections.
AB  - A history of morning and rest pain that eases with activity was found to improve
      after anti-inflammatory injections around the paratenon or within the Achilles
      bursae. The reduction in pain morbidity was significant, and the peritendinous
      steroid injections did not increase the rupture rate.

PMID- 10205701
TI  - The eighth wonder of the world: the mythology of concussion management.

PMID- 10205702
TI  - Fifty years of competitive sport for athletes with disabilities: 1948-1998.

PMID- 10205703
TI  - Sports medicine in The Netherlands: a long road to a new start.

PMID- 10205704
TI  - Complementary medicine.

PMID- 10205705
TI  - Complementary medicine.

PMID- 10205706
TI  - Performance enhancing drugs.

PMID- 10205707
TI  - Physical activity programmes.

PMID- 10205708
TI  - Evaluation of physical activity.

PMID- 10205709
TI  - An audit of the use of magnetic resonance imaging by the sports injuries service
      of a university teaching hospital.

PMID- 10205710
TI  - Information from sports injury research.

PMID- 10205711
TI  - Cognitive orientations in marathon running.

PMID- 10205713
TI  - Future of flexible bronchoscopy.
AB  - Despite some potential "threats" (Table 3), the future of bronchoscopy is likely
      full with ever expanding applications in clinical medicine and research (Tables 1
      and 2). The role of bronchoscopy in lung cancer continues to expand and the
      usefulness of newer techniques needs to be established. The role of FB is also
      ever expanding in the immuno compromised host and critically ill patients. Future
      studies, however, should concentrate on patient outcome, especially survival and
      performance status. Therapeutic bronchoscopy has been extended to many areas and
      the emphasis of future research will likely continue to be at the molecular level
      rather than on studies of better instruments for retrieval purposes. The most
      exciting developments are likely to be in the field of gene therapy, which has
      made remarkable progress in the past decade. Gene therapy can be a powerful
      technology, but several hurdles must be overcome to make gene therapy a reality
      for treating human disease in the future. As the cost of technology continues to
      challenge health care delivery systems, a major challenge for the future of
      bronchoscopy is to evaluate new technologies and applications based on their
      impact on patient outcome, survival, and management of cost.

PMID- 10205712
TI  - Tour de Farce.

PMID- 10205714
TI  - Infection control in the bronchoscopy suite. A review.
AB  - Bronchoscopy can occasionally transmit disease. Infection control in the
      bronchoscopy suite is especially important because of the risk of transmitting
      HIV or tuberculosis. Many case reports, patient series, and small studies have
      been published, but little comprehensive guidance is available for clinicians who
      wish to learn more about the problem and prevent it. We review the literature and
      describe three ways in which bronchoscopy can cause disease: by transmitting
      infections between patients, by transferring microorganisms within a patient, and
      by triggering coughing that can cause airborne infection of patients or health
      care workers. Recommendations for infection control are listed; they include
      installing powerful air filters, using disposable bronchoscope suction valves,
      manually cleaning all equipment before disinfection, controlling patient
      coughing, and in some cases, giving patients prophylactic antibiotics.

PMID- 10205715
TI  - Radiation safety for health care workers in the bronchoscopy suite.
AB  - Increased use of fluoroscopy during flexible bronchoscopy has raised concerns
      about radiation safety of health care workers in the bronchoscopy suite. We
      review the potential health risks associated with occupational radiation
      exposure, the monitoring devices available, and discuss the measures to reduce
      radiation exposure during flexible bronchoscopy.

PMID- 10205716
TI  - Transbronchial needle aspiration. An underused diagnostic technique.
AB  - Despite its proven usefulness, TBNA is not widely used. An American College of
      Chest Physicians (ACCP) survey showed that only 11.8% of pulmonologists use TBNA.
      Most pulmonologists in the 1980s were not formally trained in TBNA. This lack of
      training has unfortunately translated to minimal emphasis on TBNA in current
      training programs in a large number of institutions. Technical problems with the
      procedure (faulty site selection, incomplete needle penetration, catheter kinking
      that prevents adequate suction, etc.), the confusing array of needles, low
      diagnostic yields, unproven concerns regarding the safety of the procedure,
      inadequate cytopathology support, and bronchoscopic damage have all perpetuated
      the image of limited usefulness for this procedure. Limitations to the practice
      of TBNA are: Lack of training during fellowship Technical inadequacies Lack of
      cytopathologists trained in TBNA interpretation Fear of bronchoscope damage
      Safety issues Failure to reproduce published successes Reservations regarding
      usefulness of TBNA results Hands-on experience with TBNA, developing familiarity
      and expertise with only a few needles, and paying careful attention to anatomy,
      procedure techniques, and specimen acquisition may all help to increase yield.
      The following lists how better results can be obtained with TBNA: Preprocedure
      Review TBNA instruction tapes Attend hands-on courses Practice with lung models
      Review patient's CAT scans Familiarize with one-two cytology and histology needle
      Obtain a trained assistant Procedural Identify target site Needle to airway angle
      at least greater than 45 degrees Insert entire length of the needle Use scope
      channel to support the catheter Release suction before withdrawing needle (for
      staging) Specimen acquisition Avoid delay in preparing slides Adequate sampling
      (at least two) Use smear method for cytology specimen Analyze all samples flush
      solutions cell block Postprocedure Find an experienced cytopathologist Review
      your procedure (by watching video) Review pathology slides Acquisition of skills
      with cytology needles should precede the use of the histology needle. Increasing
      education and experience can also increase diagnostic yields. Transbronchial
      needle aspiration has been proven to be accurate in staging lung cancers,
      identifying inoperable carcinomas, and diagnosing a variety of lung diseases. Few
      complications have been encountered and the technique is less invasive and less
      costly than surgical procedures. Drawing on evidence from published literature,
      we suggest the following guidelines for TBNA: All patients presenting with
      mediastinal or hilar adenopathy or both, should have 22-ga and/or 19-ga TBNA as
      the initial procedure. These procedures would help diagnose malignant and
      nonmalignant diseases, and stage lung cancers. All patients with evidence of
      submucosal and peribronchial disease should have 22-ga needle cytology sampling.
      In patients with visible endobronchial disease, 22-ga TBNA should be optional. In
      the presence of a necrotic or a hemorrhagic tumor, or in a patient with a
      bleeding diathesis, TBNA would be helpful. In all patients with Type III and IV
      peripheral nodules, TBNA should be the initial diagnostic procedure. There
      remains no doubt about the diagnostic usefulness of TBNA. Guidelines must be
      developed to ensure that pulmonary fellows are adequately trained in this
      procedure. Regional workshops with hands-on experience targeted to practicing
      pulmonologists organized by the ACCP would help popularize the procedure. Initial
      low yields should not discourage pulmonologists from using the procedure.
      Collaboration between thoracic surgeons, oncologists, and pulmonary physicians is
      essential to set up TBNA programs within institutions. With time, as more and
      more pulmonologists attain expertise in TBNA, the full potential of this
      nonsurgical, cost-effective, and safe procedure will be realized.

PMID- 10205717
TI  - Early diagnosis of lung cancer.
AB  - Recent advances in computer-assisted image analysis, tumor biology, PCR-based
      assays, fluorescence bronchoscopy, spiral CT, endobronchial treatment modalities,
      and chemoprevention make it possible to re-examine the strategy of early
      detection in the comprehensive management of lung cancer.

PMID- 10205718
TI  - Role of bronchoscopy in AIDS.
AB  - The differential diagnosis of pulmonary disorders in the HIV-infected individual
      is broad. Clinical features and chest radiographs may point towards a diagnosis
      but cannot reliably establish one. It is important to know the conditions in
      which bronchoscopy, BAL, and TBB are likely to be diagnostic, just as it is to
      know when other invasive or noninvasive procedures may be more useful. Finally,
      the incidence of transmission of infections such as tuberculosis during
      bronchoscopy and cross-contamination of patients with an improperly sterilized
      bronchoscope, cannot be overemphasized.

PMID- 10205719
TI  - Flexible bronchoscopy in lung transplantation.
AB  - Bronchoscopy plays an indispensable role in lung transplantation. It is an
      essential part of the evaluation of potential lung donors, and it is the pivotal
      procedure in the management of lung transplant recipients. Although advances in
      immunodiagnostic methods may ultimately lead to noninvasive tests to detect
      rejection, histology will be the standard for some time, and transbronchial
      biopsy will remain the procedure of choice. Furthermore, the usefulness of
      bronchoscopy in the diagnosis of pulmonary infection after lung transplantation
      is unlikely to be supplanted by any emerging technique.

PMID- 10205720
TI  - Role of bronchoscopy in massive hemoptysis.
AB  - Massive hemoptysis accounts for a minority of all patients with hemoptysis but
      poses a major challenge for the acute and long-term treatment. Massive hemoptysis
      can lead to asphyxiation and airway obstruction, shock, and exsanguination.
      Bronchoscopy plays an integral part in managing massive hemoptysis in diagnosis
      and treatment (Table 5). Specifically, bronchoscopy allows lateralization and
      more specific localization of bleeding that is critically important for effective
      management. Furthermore, acute control of bleeding can sometimes be achieved with
      instruments and catheters placed through the bronchoscope or by agents instilled
      into the airways through the bronchoscope.

PMID- 10205721
TI  - Endobronchial laser therapy.
AB  - We have sought to briefly outline the history and current role of laser therapy
      in airway obstruction. A primary goal in the use of laser therapy is the safe,
      effective, and rapid palliation of symptoms owing to tracheal or bronchial
      obstruction. This seems clearly supported in the literature despite some
      variation in definitions as to measurement of success. Objective criteria for
      improvement has also been studied, with authors noting improvement in walk tests,
      spirometric studies, and caliber of airways after treatment in significant
      percentages of patients. Patient survival, as noted by Ramser and Beamis, may not
      be the proper endpoint when discussing therapy, which for malignant causes, is
      meant to be palliative. Noting this, there are many benign conditions that may be
      effectively treated with laser therapy with a possible "cure" for some lesions
      defined as "carcinoma in situ." We believe laser therapy in the treatment of
      airway obstruction is an important tool that has proven beneficial in the therapy
      of benign and malignant lesions of the airway. Although future studies should
      prospectively examine survival characteristics, the current evidence firmly
      supports the use of laser as a useful modality of therapy in our endeavors to
      provide palliative and potentially curative care to our patients with lung
      disease.

PMID- 10205722
TI  - Cryotherapy, electrocautery, and brachytherapy.
AB  - Since it was first used 70 years ago, brachytherapy has become an effective tool
      in the treatment with tracheal bronchial malignancy including primary and
      recurrent bronchogenic carcinoma and metastatic carcinoma. The technique has
      evolved from interstitial implantation of radioactive sources directly to the
      tumor using rigid bronchoscopy to intraluminal placement of a radioactive source
      into a polyethylene afterloading catheter placed using FB. Intraluminal
      brachytherapy is effective in palliating complications caused by malignant
      endobronchial tumors such as dyspnea, hemoptysis, intractable cough, atelectasis,
      and postobstructive pneumonia. Brachytherapy may be combined with external beam
      radiation, Nd:YAG laser therapy, and chemotherapy to enhance the palliative
      treatments of patients. The risk of severe complications from brachytherapy may
      be caused more by location of tumor being treated rather than those
      fractionations scheme. When tumor involves the mainstem bronchi and upper lobes,
      it seems prudent to obtain CT to exclude tumor invasion of the pulmonary arteries
      or considerable destruction of the bronchial wall and mediastinal invasion of the
      tumor. Patients with findings such as these should not be treated with
      endobronchial brachytherapy or treated with LDR brachytherapy. Brachytherapy is
      proved to be effective and a safe palliative treatment for endobronchial
      malignancies, but further investigations are necessary to determine the optimal
      dose scheme and its efficiency in bronchogenic carcinoma and combined with
      external beam radiation therapy or surgery or other endobronchial procedures such
      as Nd:YAG laser or cryotherapy.

PMID- 10205724
TI  - Role of bronchoscopy in asthma research.
AB  - Over the past 15 years, much has been learned about the presence of airway
      inflammation in asthma through the use of investigative bronchoscopy. It has
      become quite clear that inflammation is present even in mild asthma. In addition
      to the eosinophils, T-lymphocytes and a variety of cytokines have been identified
      to play a prominent role in asthmatic inflammation. The concept of delayed
      asthmatic response after allergen exposure and its relationship to cellular
      inflammation and airway hyper-reactivity has become more clearly established. Our
      understanding of asthmatic airway inflammation, however, is incomplete. As
      interesting as the database has been so far, investigative FB has not defined a
      unique profile for patients with asthma. Specifically, lavage or endobronchial
      biopsy has not identified parameters that help in the diagnosis, assessment of
      disease severity, prognosis, or likelihood to respond to specific therapies.
      Also, the exact relationship between parameters in lavage compared with mucosal
      biopsy and how these are related to airway hyper-reactivity and the clinical
      syndrome of asthma remains poorly understood. In this regard, it must be
      confessed that currently FB with lavage and biopsy in asthmatics needs to be
      considered as a research tool for specimen retrieval to help characterize and
      express inflammation. Although these techniques have contributed immensely to our
      understanding of asthma pathogenesis, presently these techniques do not have any
      practical role or clinical usefulness.

PMID- 10205723
TI  - Airway stents.
AB  - Considerable progress has been made since the initial stents were manufactured.
      Despite the reported side effects, cumulative evidence suggests beneficial
      effects in properly selected patients. The technology is still in evolution, and
      design modifications strive to find the perfect stent. The Dumon stent remains
      the gold standard against which the functions of all other stents are being
      measured. Unfortunately requirement for the RB for deployment has restricted
      widespread application at least in the United States. The Wallstent can be
      inserted using FB and has a great potential among the metal stents. Its biggest
      drawback is that once inserted it is difficult to remove. Studies with the
      nitinol Ultraflex and the polyester/silicone Polyflex prototype stent also show
      promise, although extensive experience and long-term follow-up data are still not
      available. It is possible that combining the strength of the tube stents with the
      flexibility of the metal stents may one day help to develop the ideal stent.

PMID- 10205725
TI  - Role of bronchoscopy in lung cancer research.
AB  - The use of bronchoscopy for research into lung cancer is mostly limited by the
      imagination of the investigator. This technique allows the scientist direct
      access to tissue in a minimally invasive manner. We have discussed some of the
      applications of this technique in better understanding lung cancer. As we move
      onward in the areas of diagnosis and treatment of lung cancer, the bronchoscope
      will remain an important research tool.

PMID- 10205726
TI  - Virtual bronchoscopy.
AB  - Three-dimensional endoluminal tracheobronchial simulations can be derived
      successfully from thoracic helical CT scans, and can reproduce the appearances of
      major endobronchial abnormalities confirmed during FB. The prospects of ever
      faster CT scanners (capable of submillimeter resolution) merged with greater
      computer power make it likely that current versions of virtual bronchoscopy
      images will seem primitive in the future. Initial descriptive reports suggest
      great potential, but the startling visual appeal of these 3-D portrayals of a
      patient's airway and mediastinal anatomy and the prospects of exploring this
      information in real time do not establish its clinical role. Such virtual
      bronchoscopy findings are generally predictable on the basis of currently
      available axial CT images alone. The extent to which these 3-D endobronchial
      renderings improve the already high predictive values of CT requires critical
      study. In their patients with lung cancer Cicero et al observed that neither the
      staging nor diagnosis was modified substantially, but virtual bronchoscopy
      contributed to enhanced understanding of the pathology of the neoplastic process.
      Whether this added perspective translates to tangible benefits for patients is an
      intriguing possibility that has yet to be proved. The unique 3-D endobronchial
      view may offer particular advantages in some individuals and contribute to the
      patient's noninvasive evaluation. Because of the already high yield of
      conventional CT, diagnostic yield alone is not likely to be the sole best measure
      of this evolving technology. Accordingly, future multidisciplinary research
      investigations will also need to prospectively address nuances of decision-making
      and measure appropriate patient outcomes. In these efforts the active dialogue
      between chest clinician and radiologist will remain essential to defining and
      realizing the true potential of virtual bronchoscopy.

PMID- 10205727
TI  - [Depression and somatic diseases. On one retrospective study of 210 patients with
      major depression hospitalized in a psychiatric hospital].
AB  - Associations between depression and somatic disorders are common and little
      studied. We present the results of a retrospective study including 210
      psychiatric inpatients, suffering from a major depressive episodes (MDE-DSM III-R
      criteria). The purpose of this study was: first, to access the prevalence of
      comorbid MDEs with somatic illness, second to describe the clinical, therapeutic
      and evolutionary characteristics of MDEs secondary to a physical trouble,
      comparatively with primary depressions and depressions secondary to another
      psychiatric disorder. A somatic comorbidity was found in 55% of patients (n =
      116), the physical illness being, in 6% of cases, causal regarding MDEs. MDEs
      with a somatic comorbidity (n = 55) are significantly different from primary MDEs
      (n = 36) and MDEs secondary to another psychiatric disorder (n = 58), regarding
      an older age at hospitalization and at first affective episode. Moreover, they
      are different from MDEs secondary to another psychiatric disorder through fewer
      past suicide attempts, more episodes with melancholic or psychotic
      characteristics and a lower frequency of tricyclic antidepressant use. Despite
      methodologically limited, these results confirm the frequency of physical
      comorbidity in depressed patients hospitalized in general hospitals, especially
      in elderly subjects. They also reflect the heterogeneity of the group of
      secondary depressions, MDEs associated with a somatic illness being closer to
      MDEs secondary to another psychiatric disorder than to primary MDEs.

PMID- 10205729
TI  - [Clinical case observations: lessons for empirical research].
AB  - Empirical studies of psychopathology are typically conducted in the goal of
      uncovering general characteristics of large samples of individuals. By contrast,
      the case study has remained a basic paradigm for understanding the causes of
      psychopathology as it is actually experienced by a given patient. However, by
      using case studies as an example, empirical researchers are rediscovering the
      importance of the individual. New data collection and analytic techniques have
      recently been applied to this effort, and considerable progress has been made to
      remove previous barriers to idiographic analyses. The present article describes
      these new applications, and discusses how empirical research can benefit from
      using case studies as a model for understanding the individual in a larger
      sample.

PMID- 10205728
TI  - [Psychiatric side effects of non-steroidal anti-inflammatory agents].
AB  - The nonsteroidal anti-inflammatory drugs (NSAIDs) are often used all over the
      world. Their psychiatric side-effects are rarely known. We report a case of
      indomethacin related depersonalization and have done a review of literature. We
      wanted to show the NSAIDs's side-effects. These are non specific, they can be
      either affective disorders, depersonalization states, hallucinations, or paranoid
      psychosis (which seems to be the most frequent). The symptomatology is easily
      suppressed, as soon as NSAIDs are stopped and/or psychotherapeutic symptomatic
      treatment is started. Different explanations are proposed: prostaglandin
      inhibition for the NSAIDs in general, indolic molecular structure (which looks
      like serotonin) for the indomethacin in particular which is the NSAID the most
      find in these side effects. There is several studies about the role of
      prostaglandin in psychiatry above all about schizophrenia. Some therapeutic
      essays were realized with prostaglandins precursors. The rest of the nosology is
      less studied.

PMID- 10205730
TI  - [Genetic epidemiology and psychiatry (I): scope and limitations of familial
      studies. Case of panic disorder].
AB  - Genetics epidemiology shed new light on multifactorial disorders for which genes
      are partly involved, for example on numerous psychiatric diseases. Nevertheless,
      each epidemiological technic has it's caracteristics and limitations. This review
      discuss the impact of aggregation studies, on the bases of an example, namely all
      aggregation studies on panic disorder. We detected through Medline thirteen
      studies, comparing 3,700 relatives of 780 probands affected with panic disorder,
      with 3,400 relatives of 720 unaffected controls. It is computed that relatives of
      patients with panic disorder have an increased risk (10.7%) for panic disorder
      than relatives of controls (1.4%), relatives from affected probands having a high
      relative risk (6.8) for panic disorder according to the meta-analysis. On the
      basis of these 13 aggregation studies, there is an important attribuable risk
      (78.3%) of "having a familial history of panic disorder" in the risk for panic
      disorder. Furthermore, the estimated heritability is 73% (73% of the total
      variance would be explained by additive genetic effects), if Reich's conditions
      are fulfilled for a valid estimation of the heritability on the basis of
      aggregation families. These studies can also be used to highlight the variability
      of expression according to gender, to show the relevance of quantitative
      approaches (versus the qualitative approach which is nearly systematically used),
      to underline the informations raised by experimental technics (such as panic
      disorder induced by lactate), and to raise the potential existence of
      phenocopies. Lastly, aggregation studies on panic disorder can help to understand
      the high comorbidity of this disorder, with other anxiety disorders and mood
      disorder.

PMID- 10205731
TI  - [Evaluation of the incidence of hospitalization of patients with psychotic
      disorders].
AB  - The aim of this study was to assess the administrative incidence of psychotic
      disorders, i.e. the incidence of first hospitalization for such disorders.
      Consecutively first-admitted patients hospitalized in 4 departments of Bordeaux's
      psychiatric hospital were included. Patients fulfilled the following inclusion
      criteria: no previous psychiatric hospitalization; aged 60 years or less; at
      least one overt psychotic symptom; clear consciousness. Patients were drawn from
      a 250,000 inhabitants urban catchment area, with an at risk population of 161,698
      inhabitants. DSM IV diagnoses were made using the Mini International
      Neuropsychiatric Instrument (MINI) as well as all available information collected
      from the patient, the relatives, and from any other informant. A complementary
      study was performed in the private psychiatric institutions and in the military
      Hospital of Bordeaux in order to assess the representativeness of the patients
      hospitalized in the state hospital. 59 patients were included during one year in
      the state hospital. The raw incidence rate was 0.37 per 1,000 (95% CI; 0.28
      0.46). We used a direct standardization on age to calculate the incidence rates
      ratio to gender. Men were over-representated in the sample, with a standardized
      incidence ratio in men compared to women equal to 1.87 (95% CI; 1.25-2.8).
      Psychotic mood disorders had the highest incidence, with an incidence rate equal
      to 0.15 per 1,000 inhabitants (95% CI; 0.09-0.21). The incidence rate of DSM IV
      schizophrenia was lower than that of psychotic mood disorders, and was equal to
      0.13 per 1,000 (95% CI; 0.08-0.18). Several studies conducted in European and
      North-American countries have recently suggested that the incidence of
      schizophrenia may have decreased in the past decades. Since few French studies on
      the incidence of such disorders have been carried out, it is not possible to
      assess whether the incidence of schizophrenia is or not decreasing in France.
      Further studies on the incidence of psychotic disorders are required in other
      French regions in order to assess the reproductibility of our results, and to
      have reference data on the incidence of psychotic disorders in the nineties.

PMID- 10205732
TI  - [Effect of fluoxetine treatment on serotonin and MHPG in 32 patients with major
      depressive disorder].
AB  - Considering the concept that depressive disorders were not only resulting from
      activity of one neurotransmitter, possible interactions between the noradrenergic
      system and a selective serotonin uptake inhibitor, fluoxetine, were investigated
      in order to test the hypothesis of noradrenergic or serotonergic involvement in
      depression. So the biological parameters (plasma and urinary MHPG, platelet
      serotonin) were evaluated by HPLC. The aim of this study was to evaluate the
      correlations between the concentrations of MHPG and serotonin in 32 melancholic
      patients treated by fluoxetine (20 mg/day) during a minimum of three weeks. The
      clinical examination with evaluation of the antidepressant effect carried out
      using the HDS/MES rating scale, allowed to divide the patients into three groups:
      responders to treatment, partial responders and non responders. In the same time,
      a control group of healthy subjects was investigated. ANOVA applied to platelet
      serotonin at day 0 showed a tendency toward heterogeneity between the three
      patient groups and the control group. The concentrations of serotonin in the
      three patients groups were highly reduced after 21 days of treatment. Concerning
      plasma and urinary MHPG there was non significant difference among the three
      patients groups at day 0 and the control groups. After treatment by fluoxetine,
      the results suggest that the urinary sulfate MHPG is an indicator of the
      metabolism of brain norepinephrine and seems to be a better turnover indicator
      than the plasma sulfate MHPG. The selective evaluation of sulfate and glucuronide
      MHPG could give a better survey of the psychobiological state of the patients
      than the total MHPG evaluation.

PMID- 10205733
TI  - [Distinction between anxiety state/trait in general practice: a descriptive
      study].
AB  - State-anxiety has been defined as a transitory emotional response involving
      unpleasant feelings of tension and apprehensive thoughts. Trait-anxiety, on the
      other hand, has been defined as a personality trait referring to individual
      differences in the likelihood that a person would experience state anxiety in a
      stressful situation. The aim of the present study was to assess trait and state
      anxiety in a population of patients consulting physicians for anxious complaints.
      Thus, patients who stopped the benzodiazepine (BZD) treatment after three months
      and those who continued it for six months were compared. Included patients were
      evaluated at inclusion (D0), after three months (M3) and after six months (M6).
      The investigator filled the Covi anxiety scale, the Raskin depression scale and a
      CGI; patients were asked to fill the Spielberger state/trait-anxiety
      questionnaire. 1,112 patients have been included, 48% considered their anxiety as
      chronic, 50% said the evolution was progressive, 87% considered it resulting of a
      trigger factor, 69% received a benzodiazepine (BZD) treatment. At D0: Covi
      anxiety score was 5.3 +/- 2.3 points, STAI I (state-anxiety) score was 57.4 +/-
      12.2 points and STAI II (trait-anxiety) score was 52.7 +/- 10.2 points. At M3,
      all scores decreased, and 85% were considered as ameliorated, but differences
      were significant (p = 0.0001) at M6. When comparing at D0 patients who stopped
      BZD treatment at M3 and those who continued it, some differences appeared. In
      fact subjects who stopped the treatment had lower score at the STAI II, presented
      significantly less flushes (p = 0.01), less tremor (p = 0.04) and less
      feverishness (p = 0.05). Their score at Covi tended to be lower (p = 0.11). The
      severity of the disease, evaluated with the CGI, was also lower for the patients
      who stopped the BZD treatment. The trait-anxiety appeared as a good predictor of
      the efficacy of the BZD treatment. In fact, the trait-anxiety refers to a
      tendency to be anxious and higher anxiety necessitates longer treatment. The
      treatment response was less important in the patients who continued the treatment
      at M3, indicating the presence of residual anxiety in these patients.

PMID- 10205734
TI  - [Stroop test and schizophrenia].
AB  - Utilization of the Stroop test with schizophrenic subjects is reviewed from 32
      studies published since 1960. This test, in which subject has to name the color
      of color-words which are congruent or incongruent, is much used as a selective
      attention test. Its specific disturbance in schizophrenics would confirm the
      overload of consciousness with unsignificant non filtered information, probably
      due to lowering of frontal functions. Stroop effect is not always raised in these
      patients, especially when general slowing is taken into account. Technical
      differences modify the test power and can explain contradictory results. The
      thought disorder symptom seems the most correlated with the results of the test,
      and particular sensitiveness of paranoid form has been argued. Neuroleptics do
      not seem to act on Stroop effect. Factors explaining the great variability of
      patients in this test are not fully put in light. One hypothesis, already raised,
      is that the test is linked to a particular attentional constitutional aptitude,
      and whose relations with the illness are to be explained.

PMID- 10205735
TI  - [The discovery of haloperidol].
AB  - Haloperidol was synthesized on the 11th of February 1958 by Bert Hermans at the
      Janssen Laboratories, Beerse, Belgium. Simple but ingenuous methods of animal
      pharmacology suggested to Paul Janssen and his collegues that this butyrophenone
      derivative, called R1625, then halop-peridol, would be of great interest:
      qualitatively, the pharmacological action of R1625 was similar to chlorpromazine,
      but R1625 was very more powerful since it produced effects with much smaller
      doses than chlorpromazine. Soon after the synthesis and animal studies,
      haloperidol was administered in humans by Divry, Bobon et Collard, psychiatrists
      at the Liege Hospital. The first clinical publication, on the 28th of October,
      1958, described the effects of haloperidol in agitation states. The subsequent
      clinical studies, including those of the prestigious French school of Sainte-Anne
      hospital, confirmed that haloperidol belongs to the pharmacological family of
      neuroleptics, as it was defined by J. Delay and P. Deniker in 1955. These
      clinical studies demonstrated also that haloperidol was particularly active
      against delusions and hallucinations. Numbers of chronically inpatients were able
      to leave hospital and to live home thanks to this new drug, which remains one of
      the more prescribed neuroleptics 40 years after its discovery.

PMID- 10205736
TI  - [Grapefruit juice as a contraindication? An approach in psychiatry].
AB  - The authors investigated in this preliminary study the influence of grapefruit
      juice on the metabolism of two tricyclic antidepressants. An increase of plasma
      concentrations is observed indeed for many drugs when administered concomitantly
      with grapefruit juice. This effect was mainly attributed to inhibition of
      cytochrome P450 1A2 and 3A4 enzymes by naringenin. These isoenzymes are involved
      too in the metabolism of many psychotropic drugs. Only two benzodiazepines
      (midazolam and triazolam) were studied in the conditions of grapefruit juice
      association. All these studies are performed in healthy subjects and with a study
      design very different from the clinical conditions. On the basis of these
      considerations, the authors hypothesized that grapefruit juice should inhibit
      tricyclic antidepressant metabolism and thus increase the bioavailability of
      these drugs. They want to precise if this possible drug plasma level increase
      could be clinically important for depressed patients. Fourteen depressed
      inpatients were selected for the study. Seven of them received amitriptyline (100
      to 150 mg/d) and the seven others clomipramine (112.5 to 225 mg/d). Tricyclic
      antidepressant and desmethylated metabolite plasma levels were determined on four
      occasions. The first and second day samples were obtained to determined the
      plasma level intraindividual variability of antidepressants. On the third and
      fourth days, plasma levels were determined after an oral coadministration of the
      antidepressant and 250 ml of pure and fresh grapefruit juice. One patient was
      excluded from the study due to the coadministration of clomipramine and
      fluvoxamine. There is indeed a major drug-interaction between these two drugs,
      and the tricyclic antidepressant plasma levels of this patient were in the toxic
      range, without side effect. In this group of patients, there was no metabolic
      interaction between amitriptyline and grapefruit juice. But the mean plasma
      levels of clomipramine and desmethylclomipramine increased after coadministration
      of this juice (+4.5% and +10.5% respectively). The authors concluded that with
      these preliminary results, the potential clinical relevance of this interaction
      cannot be estimated.

PMID- 10205737
TI  - [Influence of personality disorder on the course of manic-depressive illness].
AB  - In these past years, comorbidity of manic-depressive illness with personality
      disorders were the subject of many studies. In order to study the influence of
      personality disorder on the course of the disease, the authors have compared a
      group of manic depressive patients with personality disorders to an other group
      of manic depressive patients without personality disorders. The comparison
      between the outcome and prognosis of each group has leaded to the conclusion that
      manic depressive patients with personality disorders evaluate worse than those
      without personality disorders: they are more often hospitalized and have more
      suicide attempts, they are more vulnerable to stress factors and finally they
      have low scores on the Global Assessment of Functioning scale (GAF).

PMID- 10205738
TI  - [determining factors of depression in multiple sclerosis: review of the
      literature].
AB  - Depression is considered to occur more frequently in multiple sclerosis than in
      other chronic organic disorders. The determining factors of this specific
      association have been appraised by most authors in a dichotomic manner,
      confronting organic to psychogenic hypotheses. To assess these hypotheses two
      investigational methods have been used in the literature: either the search for
      correlations between depression and other parameters linked to the neurologic
      process, or the comparison of the course of neurologic and thymic symptoms.
      Systematically scrutinizing this literature enabled us to discuss its findings as
      well as its methodologic and conceptual limitations.

PMID- 10205739
TI  - [The nature of adaptive evolutionary changes: fitness and potential].
AB  - Ecological potential of an individual can be defined as its viability in the
      broad sense including the ability to reproduce in various environments. From the
      biological viewpoint, ecological potential as a fundamental property of an
      organism is more important than fitness in the genetic sense, which is estimated
      as the relative rate of reproduction. In essence, fitness reflects the level of
      implementation of the biological potential. In the process of evolution,
      regulatory selection results in an increase of fitness: selected forms reproduce
      more successfully as the population size increases. By contrast, individuals with
      high ecological potential are more advantageous when the population size
      decreases, because the probability of their survival in adverse environments is
      high. Thus, high levels of fitness and ecological potential are achieved via
      operation of different types of selection.

PMID- 10205740
TI  - [Cryptic heterokaryons in Saccharomyces cerevisiae strains: pseudopleiotropic
      suppression in the multiple marked YPH857 strain].
AB  - The yeast strain YPH857 carrying multiple genetic markers was shown to segregate
      clones that had the pleiotropic suppression phenotype. The phenotype was
      designated Ppsu+. This suppression involves deletion alleles of the TRP1 and HIS3
      genes and an insertion in the URA3 gene. Unlike the original YPH857 culture that
      carries an unidentified mutation of resistance to cycloheximide, the Ppsu+ clones
      exhibited a decreased level of resistance to this inhibitor of protein synthesis.
      In addition, they have a lower mating ability and can produce asci on a standard
      medium for sporulation. A comparative analysis of total DNA from the YPH857
      strain and Ppsu+ segregants by Southern blotting provided evidence for the
      presence of an extraneous nucleus in these segregants. Ppsu+ strains were shown
      to contain wild-type alleles, apart from deletion and insertional alleles typical
      for the YPH857 strain. Moreover, they contain the 2 microns DNA of the Scp3 type
      with deletion of one of the two EcoRI and HpaI recognition sites (whereas the 2
      microns DNA of YPH857 belongs to the Scp1 type) and exhibit heterogeneity with
      respect to the presence of one EcoR1 recognition site in the gene of 5S ribosomal
      RNA. It was supposed that the "cryptic" nucleus belongs to a strain of low
      viability and can survive as an unexpressed DNA in a small fraction of cells.
      Nuclei from the cryptic and YPH857 strains can be fused at a low rate to yield
      Ppsu+ cells capable of sporulation. In certain cases, a Ppsu+ clone may be
      heterogeneous: some of its cells contain nuclei in an unfused heterokaryotic
      state. This assumption has been confirmed by selecting Cyhr colonies with the
      original YPH857 genome among Ppsu+ clones on the cycloheximide-containing medium.

PMID- 10205741
TI  - [Cryptic heterokaryons in Saccharomyces cerevisiae strains. Model experiments].
AB  - Heterokaryons capable of segregating clones of different phenotypes were obtained
      in saccharomycetes yeast. Clones expressing phenotypic traits encoded by the
      nuclear genome of one parent and the mitochondrial genome of another were shown
      to contain cells that carried the second phenotypically silent nucleus. The
      cryptic nucleus can be uncovered by growing these "cytoductants" on the
      corresponding medium. The use of strains carrying an insertion in the URA3 gene
      and the endogenic plasmid, 2 microns DNA, made it possible to detect this nucleus
      by blot hybridization.

PMID- 10205742
TI  - [Phenotypic and genotypic structure of a natural Drosophila population for
      meristic morphologic characters and its seasonal changes].
AB  - A natural population of Drosophila was genetically heterogeneous in the number of
      sternopleural bristles and the number of arista branches. In the summer, these
      characters had a low mean value and high coefficient of variation: in autumn,
      this relationship was reversed; in late spring, the values of the mean and
      coefficient of variation were intermediate. The dynamics of the character mean
      was determined by changes in phenotypic and genotypic composition of the
      population, which was examined during different seasons of the year. On average,
      the number of sternopleural bristles was higher, and the number of arista
      branches was lower in females than in males. The number of sternopleural bristles
      exhibited a higher phenotypic and genotypic variation than the number of arista
      branches.

PMID- 10205743
TI  - [Discordance and cosegregation of swine halothane susceptibility and 1843 C-T
      mutation of their RYR1 locus responsible for the ryanodine receptor].
AB  - In two Siberian swine populations, the halothane test and PCR were used to
      determine the halothane susceptibility of the animals and to reveal a point
      mutation in their RYR1 gene, respectively. No correlations were found between the
      halothane susceptibility of an animal and the presence or absence of a point
      mutation at its RYR1 locus. However, the population changes in halothane
      susceptibility and the frequency of the mutation proved to be unidirectional. In
      the studied swine populations, the halothane-susceptible animals had no
      hyperthermia and the frequencies of their Hal and RYR1 genes changed similarly.
      These phenomena along with the phylogenesis of malignant hyperthermia and the
      porcine stress syndromes (PSS) in different breeds are discussed. In the
      populations studied, PSS is suggested to be under the polygenic control.

PMID- 10205744
TI  - [Comparative analysis of Ayrshire and Black Pied cattle breeds by
      histocompatibility markers].
AB  - Distribution of BoLA-A antigens and BoLA-DRB3 alleles was studied by means of the
      microlymphocytotoxic test (BoLA-A) and the PCR-RFLP method (BoLA-DRB3) using
      restriction endonucleases RSAI, HaeIII, and XhoII in Ayrshire (n = 127) and Black
      Pied (n = 129) cattle breeds. Comparative analysis of profiles for class I
      antigens revealed significant differences in the frequencies of antigens W2, W6,
      W10, W31, W44, W15, and W19 (P > 99%). The studied breeds also differ in the
      spectrum of BoLA-DRB3 alleles and distribution of their frequencies.
      Heterogeneous allele frequency profile was detected in Ayrshire cattle: five of
      18 detected alleles (DRB3.2*7, *8, *10, *24, and *28) accounted for 77%. Allele
      DRB3.2*7 (37.6%), which is classed with rare alleles in Black Pied cattle is the
      most common in Ayrshire cattle. The observed heterozygosity level in the combined
      sample of Black Pied breed (0.836) is higher than in Ayrshire breed (0.070). In
      both breeds, the heterozygosity level was studied in the groups of healthy and
      ill with persistent lymphocytosis (caused by bovine leukemia virus) animals and
      in the group of virus carriers in Ayrshire breed. In ill animals, a decrease in
      the observed heterozygosity level was detected, as compared to healthy animals
      and the expected heterozygosity level. The observed heterozygosity level exceeds
      the expected one in virus carriers. The detected features of the heterozygosity
      level in the studied groups allow the heterozygosity level for locus BoLA-DRB3 to
      be considered a nonspecific factor of resistance to leukemia and are heterozygous
      animals to have higher resistance to bovine leukemia. The presence of a larger
      proportion of highly productive animals (the annual productivity of more than
      7000 kg) in the group of ill Ayrshire cattle animals, as compared to healthy
      animals to established. To increase resistance to bovine leukemia, the obtained
      data indicate the importance of the control of heterozygosity level and genetic
      diversity for gene BoLA-DRB3 in cattle herds.

PMID- 10205745
TI  - [Distribution of ABO and Rhesus phenotypes and genes in the population of Kursk
      region].
AB  - The distributions of AB0 and Rhesus phenotypes and the corresponding genes in the
      population of Kursk oblast were studied. Based on these data, genetic
      differentiation of rural populations with respect to the d gene frequency was
      revealed. The differentiation was determined by the differences in the genetic
      and demographic structure of these rural populations. The frequency of
      homozygotes for the recessive gene d and the incidence of malformations affecting
      the children's viability increased with an increase in the inbreeding level of a
      population. Genetic distances between the population of Kursk oblast and other
      populations were estimated.

PMID- 10205746
TI  - [Population-demographic structure of the population of Kursk region:
      anthropometric profile of newborn children].
AB  - Based on the characteristics of body height and weight in 4905 newborns, the
      population-genetic structure of the rural raions (districts) of Kursk oblast
      (region) and in the city of Kursk was determined. An "adaptive norm area" with
      respect to body weight and height was distinguished for newborns in Kursk oblast.
      On the average, the anthropometric parameters of 20% of infants from the studied
      populations fell within this area. The height and growth of newborns exhibited a
      pronounced geographic variation and depended on the level of urbanization, as
      well as the sex and the health status of the newborns. In district populations,
      the body height and the variances of the body height and weight increased with an
      increase in endogamy. Therefore, the relative numbers of newborns with large
      values of both weight and height, as well as those with a medium body height and
      a small body weight, were increased. Conversely, the relative numbers of newborns
      with a low weight and height and with a disturbed weight-height correlation were
      decreased.

PMID- 10205747
TI  - [Polymorphism of the angiotensin I-converting enzyme gene in diabetic retinopathy
      patients and type 2 diabetes mellitus patients with myocardial infarction].
AB  - The insertion/deletion polymorphism (I/D) of the angiotensin I-converting enzyme
      gene (ACE) was examined in type I diabetes mellitus patients (DM) with (n = 31),
      or without (n = 33) retinopathy, and in type 2 DM patients with either myocardial
      infarction (MI; n = 75), or with (n = 37), or without (n = 178) retinopathy. No
      association between the ACE gene and retinopathy in type 1 and type 2 DM patients
      was revealed. In the type 2 DM patients with MI, a statistically significant (P <
      0.05) elevation of the D allele frequency (64%) compared to that without MI
      (55.3%), together with statistically nonsignificant prevalence of the DD
      homozygotes (41% versus 30.6%) was observed. Our data indicate that the D allele
      (RR 1.43) and DD genotype (RR 1.75) are risk factors for myocardial infarction in
      the type 2 DM patients.

PMID- 10205749
TI  - [Allocation problems within the context of limited financial resources].

PMID- 10205748
TI  - [Ethics in medicine: needs and forms].

PMID- 10205750
TI  - [Ethical problems in the area of intensive care medicine].

PMID- 10205751
TI  - [Allocation problems within the scope of organ transplantation].

PMID- 10205752
TI  - [Euthanasia--assisted suicide].

PMID- 10205753
TI  - [Definition of death and references on brain death, partial brain death and heart
      death].

PMID- 10205754
TI  - [Ethical problems within the context of genetic counseling and diagnosis].

PMID- 10205755
TI  - [Diagnostic imaging in intensive care. Techniques, indications, diagnostic signs-
      II].

PMID- 10205756
TI  - [Recurring vertigo and syncope in a patient with eosinophilia].

PMID- 10205758
TI  - [Hyperhidrosis].

PMID- 10205757
TI  - [Somnolence and vomiting in a patient after parathyroid gland carcinoma surgery].

PMID- 10205759
TI  - [Monoclonal antibodies in colorectal carcinoma].

PMID- 10205760
TI  - [How does one calculate life expectancy in relation to risk factors?].

PMID- 10205761
TI  - [Stem cell reserve after autologous blood stem cell transplantation].

PMID- 10205762
TI  - [Proton pump inhibitor in ulcer disease?].

PMID- 10205763
TI  - [Active hepatitis B vaccination in ulcerative colitis treated with azathioprine].

PMID- 10205764
TI  - [Congenital thrombophilia. Hormonal contraception/antithrombotic therapy in
      pregnancy].

PMID- 10205765
TI  - [Prevention of recurrent alcoholism with acamprosate. Neurobiological principles
      and clinical results].

PMID- 10205767
TI  - [Unconventional, alternative therapy measures in oncology].

PMID- 10205766
TI  - ["Routine laboratory studies"].

PMID- 10205768
TI  - Analysis of nonlinear and nonsteady state hepatic extraction with the dispersion
      model using the finite difference method.
AB  - A numerical calculation method for dispersion models was developed to analyze
      nonlinear and nonsteady hepatic elimination of substances. The finite difference
      method (FDM), a standard numerical calculation technique, was utilized to solve
      nonlinear partial differential equations of the dispersion model. Using this
      method, flexible application of the dispersion model becomes possible, because
      (i) nonlinear kinetics can be incorporated anywhere, (ii) the input function can
      be altered arbitrarily, and (iii) the number of compartments can be increased as
      needed. This method was implemented in a multipurpose nonlinear least-squares
      fitting computer program, Napp (Numeric Analysis Program for Pharmacokinetics).
      We simulated dilution curves for several nonlinear two-compartment hepatic models
      in which the saturable process is assumed in transport or metabolism, and
      investigated whether they could definitely be discriminated from each other.
      Preliminary analysis of the rat liver perfusion data of a cyclic pentapeptide, BQ
      123, was performed by this method to demonstrate its applicability.

PMID- 10205769
TI  - Quantitative structure-pharmacokinetics relationships: II. A mechanistically
      based model to evaluate the relationship between tissue distribution parameters
      and compound lipophilicity.
AB  - The tissue-to-unbound plasma distribution coefficients (Kpus) of 14 rat tissues
      after i.v. administration of nine 5-n-alkyl-5-ethyl barbituric acids, determined
      in a previous study, were used to identify a model of the relationship between
      tissue distribution and lipophilicity of the homologs, expressed in terms of
      their octanol to water partition ratio, P. Based on mechanistic considerations
      and assumptions, the parameter model was expressed as Kpu tau = fw.tau [1 + a tau
      (nPt.tau)Pb tau], where fw.tau is the tissue water content. (nPt. tau) is the
      binding capacity of the tissue, n is the number of the binding sites, a tau and b
      tau are the parameters of the relationship Ka tau = a tau Pb tau; and Ka tau is
      the binding association constant of each tissue. The parameter model was
      linearized and fitted to the predetermined Kpu values, yielding correlation
      coefficients ranging between .940 and .997. The predictive performance of the
      parameter model was evaluated using a leave-one-out procedure with subsequent
      computation of the mean prediction error (ME = measurement of the prediction
      bias) and the square root of the mean squared prediction error (RMSE =
      measurement of the prediction accuracy). The ME varied between -22.48 and 61.14%,
      indicating a slight tendency for overpredicting. The RMSE was between 24.73 and
      102% for the individual tissues across the different homologs; and between 28.33
      and 85.2% for the individual homologs across the different tissues. The
      apparently high Kpu prediction errors, when translated through the low
      sensitivity of the barbiturate whole-body physiologically based pharmacokinetic
      model, established previously, leads to predicted tissue concentration-time
      profiles within 5 to 20% of the original ones. Therefore, it is concluded, that
      the identified mechanistically based model is a good predictor of the tissue-to
      unbound Kpus in the rat tissues.

PMID- 10205770
TI  - Pharmacokinetic-pharmacodynamic modeling of tolmetin antinociceptive effect in
      the rat using an indirect response model: a population approach.
AB  - The relationship between the pharmacokinetics and the antinociceptive effect of
      tolmetin was characterized by an indirect model using a population approach.
      Animals received an intra-articular injection of uric acid in the right hindlimb
      to induce its dysfunction. Once dysfunction was complete, rats received an oral
      tolmetin dose of 1, 3.2, 10, 31.6, 56.2 or 100 mg/kg and antinociceptive effect
      and blood tolmetin concentration were simultaneously evaluated. Tolmetin produced
      a dose-dependent recovery of functionality, which was not directly related to
      blood concentration. An inhibitory indirect response model was used based on
      these response patterns and the fact that tolmetin reduced nociception by
      inhibiting prostaglandin synthesis. Pharmacokinetic (PK) and pharmacodynamic (PD)
      data were simultaneously fitted using nonlinear mixed effects modeling (NONMEM)
      to the one-compartment model and indirect response model. The individual time
      courses of the response were described using Bayesian analysis with population
      parameters as a priori estimates. There was good agreement between the predicted
      and observed data. Population analysis yielded a maximal inhibition of the
      nociceptive response of 76% and an IC50 of 9.22 micrograms/ml. This IC50 is
      similar to that for tolmetin-induced prostaglandin synthesis inhibition in vitro
      (3.0 micrograms/ml). The present results demonstrate that mechanism-based PK-PD
      analysis using a population approach is useful for quantitating individual
      responses as well as reflecting the actual mechanism of action of a given drug in
      vivo.

PMID- 10205772
TI  - Estimating potency for the Emax-model without attaining maximal effects.
AB  - The most widely applied model relating drug concentrations to effects is the Emax
      model. In practice, concentration-effect relationships often deviate from a
      simple linear relationship but without reaching a clear maximum because a further
      increase in concentration might be associated with unacceptable or distorting
      side effects. The parameters for the Emax model can only be estimated with
      reasonable precision if the curve shows sign of reaching a maximum, otherwise
      both EC50 and Emax estimates may be extremely imprecise. This paper provides a
      solution by introducing a new parameter (S0) equal to Emax/EC50 that can be used
      to characterize potency adequately even if there are no signs of a clear maximum.
      Simulations are presented to investigate the nature of the new parameter and
      published examples are used as illustration.

PMID- 10205771
TI  - Integrated pharmacokinetic-pharmacodynamic model for acetaminophen, ibuprofen,
      and placebo antipyresis in children.
AB  - A descriptive profile for antipyretic drug action has been documented for
      children. However, a linked pharmacokinetic-pharmacodynamic (PK/PD) model is
      central to the understanding of antipyretic drug action in febrile children. This
      was examined for previously reported data from 178 febrile children who received
      a single oral dose of acetaminophen (APAP) (12.5 mg/kg), ibuprofen (IBU) (5 or 10
      mg/kg), or placebo. Rectal temperatures and plasma levels (microgram/ml) of APAP
      and IBU were measured for up to 12 hr after drug administration. Nonlinear
      regression analyses were applied to these measurements and yielded simultaneous
      solutions of an integrated one-compartment PK, link, and Sigmoid Emax effect
      model in 102/153 febrile children given APAP or IBU. The PK parameters (tlax, k
      alpha, beta, T1/2 beta, AUC0-infinity, Vd/F, and Clp/F) were not different than
      those reported previously, except the APAP k alpha was significantly lower. The
      link component yielded keos of 0.58 +/- 0.06 (mean +/- SE), 0.70 +/- 0.11 and
      0.57 +/- 0.11 hr-1 for APAP, IBU05, and IBU10, respectively; the Sigmoid Emax
      component yielded EC50s (microgram/ml) and sigmoidicity (gamma) of 4.63 +/- 0.39
      and 3.98 +/- 0.42 for APAP, 11.33 +/- 1.35 and 3.97 +/- 0.58 for IBU05 and 12.83
      +/- 1.89 and 4.27 +/- 0.63 for IBU10. On visual inspection of the efficacy-time
      profiles of the febrile children, a number of them had an apparent linear
      function (slope; delta degree C/hr) and/or a sinusoidal cyclic function
      "confounding" standard approaches to PD analysis. Thus, the temperature profiles
      of 91/102 children given APAP or IBU required the addition of a slope (delta
      degree C/hr) and/or a sinusoidal cyclic function to the Sigmoid Emax component to
      fit the data satisfactorily. All 22 children given a placebo also required a
      slope and/or a cyclic function in their PD model. The residual delta degree Cs
      (observed-predicted) of the placebo group were not significantly different from
      0. Thus, no placebo antipyretic effect was observed. Dose dependency of IBU AUC0
      infinity was confirmed; doubling the dose from 5 to 10 mg/kg increased the AUC0-
      >infinity by only 1.5-fold. The confounding effect of initial temperature (Tempi)
      on antipyretic efficacy in all treatment groups except placebo was also confirmed
      to expose nonlinear pharmacodynamics. A significant (p = 0.03) contribution of
      Tempi (but not age) on the value of the slope function was found. There was no
      consistent effect of age or Tempi on the cyclic component of the integrated model
      of antipyresis. In addition, a multiple linear relationship of age and Tempi was
      observed with a large number of the PK, link, and PD variables in those who
      received IBU. Dose, age, and Tempi interacted with beta in a significant multiple
      linear relationship with AUC0-infinity. The effects of IBU dose, age, and Tempi
      are pervasive and cascade down the chain of events leading to the PD response.
      The etiology of pyresis may create the slope function, the magnitude of which may
      be partially due to the underlying disease. In some cases, the cyclic function
      may be explained by temperature regulation. Regardless of their cause, both
      confound analysis of drug action and make the simple, unmodified Sigmoid Emax
      effect model less than satisfactory for interpretation of antipyretic drug
      effects. The influence of Tempi on the magnitude of antipyretic drug response is
      also a finding with major impact on PD investigations of antipyretic medications.
      In children receiving IBU, dose and age are also confounders, in addition to
      Tempi. A multiplicity of covariables must be taken into account when developing
      appropriate dosing regimens for these antipyretics in febrile children.

PMID- 10205773
TI  - Optimal experimental design for precise estimation of the parameters of the axial
      dispersion model of hepatic elimination.
AB  - The axial dispersion model of hepatic drug elimination is characterized by two
      dimensionless parameters, the dispersion number, DN, and the efficiency number,
      RN, corresponding to the relative dispersion of material on transit through the
      organ and the relative efficiency of elimination of drug by the organ,
      respectively. Optimal design theory was applied to the estimation of these two
      parameters based on changes in availability (F) of drug at steady state for the
      closed boundary condition model, with particular attention to variations in the
      fraction of drug unbound in the perfusate (fuB). Sensitivity analysis indicates
      that precision in parameter estimation is greatest when F is low and that
      correlation between RN and DN is high, which is desirable for parameter
      estimation, when DN lies between 0.1 and 100. Optimal design points were obtained
      using D-optimization, taking into account the error variance model. If the error
      variance model is unknown, it is shown that choosing Poisson error model is
      reasonable. Furthermore, although not optimal, geometric spacing of fuB values is
      often reasonable and definitively superior to a uniform spacing strategy. In
      practice, the range of fuB available for selection may be limited by such
      practical considerations as assay sensitivity and acceptable concentration range
      of binding protein. Notwithstanding, optimal design theory provides a rational
      approach to precise parameter estimation.

PMID- 10205774
TI  - Cardiovascular and metabolic responses to intermittent umbilical cord occlusion
      in the preterm ovine fetus.
AB  - OBJECTIVE: To determine the cardiovascular and metabolic responses to umbilical
      cord occlusion in the preterm ovine fetus and the impact of repetitive
      intermittent insults over a 4-day period. METHODS: Repetitive umbilical cord
      occlusions (experimental group, n = 7; control group, n = 7) were performed daily
      (112-115 days' gestation, term = 147 days). Mean arterial pressure (MAP), fetal
      heart rate (FHR), and FHR variation were monitored, and arterial blood was
      sampled at predetermined intervals. RESULTS: During umbilical cord occlusions,
      arterial oxygen pressure (PaO2) (approximately 17 mmHg) and glucose
      (approximately 0.3) millimoles per liter (mmol/L) fell and arterial carbon
      dioxide pressure (approximately 8 mmHg) rose (P < .01) to a similar extent on
      days 1 and 4. Umbilical cord occlusion produced a rise in lactate over the course
      of successive umbilical cord occlusions each day, the magnitude of which tended
      to be reduced by day 4 (0.3 +/- 0.1 versus 0.6 +/- 0.1 mmol/L). Control hour FHR
      and MAP were unaltered over the 4 days, but the delta (delta) FHR to delta PaO2
      ratio during umbilical cord occlusions was less on day 4 than on day 1 (6.0 +/-
      0.4 versus 10.9 +/- 1.5 beats per minute/mmHg; P < .01). During occlusion hours,
      high FHR variation episodes, as a measure of fetal activity, were reduced (14.6
      +/- 1.5 versus 4.2 +/- 1.3 min/h; P < .01), whereas the reduction in short-term
      (7.4 +/- 0.7 to 5.8 +/- 0.6 milliseconds; P < .05) and long-term (34.9 +/- 2.7 to
      30.0 +/- 0.6 milliseconds; P < .05) FHR variation reached significance only on
      day 4. CONCLUSION: The increase in lactate and reduced high-FHR variation
      episodes over successive umbilical cord occlusions may affect fetal growth and
      development. Furthermore, repeated umbilical cord occlusions over several days
      alter the preterm FHR response to subsequent stresses, suggesting an altered
      chemoreflex response.

PMID- 10205775
TI  - Noninvasive determination of fetal RhD status using fetal DNA in maternal serum
      and PCR.
AB  - OBJECTIVE: Because prenatal testing of fetal RhD status by amniocentesis carries
      small yet finite risks to the fetus and mother, this study sought to determine
      whether fetal DNA in maternal serum could be used to detect fetal RhD status by
      polymerase chain reaction (PCR). METHODS: A retrospective analysis was made of
      frozen serum specimens from 20 sensitized RhD-negative pregnant women (ranging
      from 15.0 to 36.0 weeks' gestation) who were confirmed by serology at birth to
      have been carrying RhD-positive fetuses. Eleven serum specimens from RhD-negative
      individuals served as controls. DNA was isolated from serum and used in two PCR
      based methods to detect a 99 base pair (bp) DNA fragment specific for the RhD
      gene and a 113 bp fragment specific for the RhCE gene as control. RESULTS:
      Overall, in 14 (70%) of 20 RhD-positive fetuses the 99 base pair RhD-specific PCR
      product was detected. There was no false positive detection among the 11 control
      serum specimens. CONCLUSION: The results illustrate the ability to detect fetal
      RhD sequences in maternal serum of sensitized women. Moreover, the findings
      demonstrate that fetal single-gene disorders can be detected prenatally by using
      DNA isolated only from maternal serum.

PMID- 10205776
TI  - Leptin and gestational weight gain: relation of maternal and cord blood leptin to
      birth weight.
AB  - OBJECTIVES: To determine maternal serum leptin concentrations throughout normal
      pregnancy, as well as cord blood leptin concentration, and to correlate serum and
      cord blood leptin levels with gestational weight gain and birth weight,
      respectively. METHODS: This study comprised 52 normal pregnant women, including
      11 in the first, 19 in the second, and 22 in the third trimester, in addition to
      30 healthy, fertile nonpregnant women of comparable age and with normal body mass
      index (BMI). Maternal blood and fetal cord blood samples were withdrawn from the
      normal, healthy pregnant women and the nonpregnant controls for the determination
      of serum leptin by a specific radioimmunoassay. RESULTS: Maternal serum leptin
      concentrations in the first trimester did not differ significantly from those of
      healthy nonpregnant control subjects, whereas leptin concentrations in the second
      and third trimesters were elevated significantly. There were significant positive
      correlations between maternal serum leptin concentration and gestational age,
      gestational weight, and BMI. Cord blood leptin concentration correlated
      positively with birth weight and third trimester maternal serum leptin.
      CONCLUSION: Elevated serum leptin is associated with maternal adiposity and risk
      of developing large for gestational age infants.

PMID- 10205777
TI  - Methylenetetrahydrofolate reductase polymorphism, folate, and susceptibility to
      preeclampsia.
AB  - OBJECTIVES: To test the hypothesis that the common missense mutation of 5,10
      methylenetetrahydrofolate reductase (MTHFR) (677 C to T, ala to val) is more
      prevalent among nulliparous preeclamptic women compared with control and
      transient hypertension of pregnancy patients. The correlation of the MTHFR
      T677/T677 genotype in mothers and fetuses was also investigated to test for
      possible maternal-fetal interactions. Lastly, possible differences in serum
      folate concentrations between control and preeclampsia patients and the
      possibility of a correlation between serum folate and MTHFR genotype were
      investigated as well. METHODS: The MTHFR genotype was determined for 114 control
      subjects, 99 preeclamptic patients, and 24 patients with transient hypertension
      of pregnancy by a polymerase chain reaction/restriction fragment length
      polymorphism (PCR) method. To ensure homogeneity of ethnic background, only
      samples from white women were analyzed. Results were analyzed with a chi 2 test
      for homogeneity. Serum folate was determined by radioimmunoassay (RIA). RESULTS:
      The prevalence of the MTHFR T677/T677 genotype was not significantly different
      between the populations studied. There was no significant difference in the
      prevalence of the MTHFR T677/T677 genotype between the infants of preeclamptic
      and control mothers. Furthermore, there was no difference in serum folate
      concentrations between control and preeclampsia patients, and there was no
      correlation between serum folate and MTHFR genotype. CONCLUSION: These data
      suggest that contrary to previous published reports, the C677T missense mutation
      of MTHFR is not a risk factor for preeclampsia in this nulliparous patient
      population. Furthermore, this mutation is not related to serum folate status in
      late pregnancy.

PMID- 10205778
TI  - Beneficial effects of estrogen on cardiac stunning in female rabbits.
AB  - OBJECTIVE: To determine the effect of estrogen treatment on the contractile,
      relaxation, and chronotropic responses of hearts of female rabbits to cessation
      of perfusion. METHODS: Adult female rabbits were treated either with estradiol or
      with the vehicle (control). The hearts were then isolated and perfused at
      constant pressure by the Langendorff technique. A saline-filled balloon connected
      to a pressure transducer was inserted in the left ventricle in order to assess
      the mechanical function of the isolated heart. Cardiac stunning was induced by
      halting the perfusion of the coronary vasculature for four successive periods of
      1, 3, 5, and 5 minutes, followed by reperfusion between nonperfusion periods.
      Changes in cardiac function induced by the cessation of perfusion were assessed
      by monitoring the changes in heart rate and in left ventricular pressure
      ([dP/dt]max as an index of ventricular contractility and [dP/dt]min as an index
      of ventricular relaxation). Changes in coronary flow were determined at baseline
      and following reperfusion. RESULTS: Halting coronary perfusion decreased
      (dP/dt)max, and (dP/dt)min and slowed left ventricular contractions both in
      control and in estrogen-treated hearts. The depressant effects of flow cessation
      on left ventricular (dP/dt)max and (dP/dt)min were smaller in estrogen-treated
      hearts than in control hearts. Treatment with estrogen had no effect on the
      changes on the heart rate in responses to cessation of flow and to reperfusion.
      Treatment with estrogen increased coronary flow by 40%. Coronary reperfusion
      increased coronary flow transiently, but the effects did not differ significantly
      between control and estrogen-treated hearts. CONCLUSION: Short-term treatment of
      adult female rabbits with doses of estrogen that are physiologic for the rabbit
      exerts a protective effect on cardiac contractility from repetitive periods
      without perfusion.

PMID- 10205779
TI  - Low-dose follicular-phase cocaine administration disrupts menstrual and ovarian
      cyclicity in rhesus monkeys.
AB  - OBJECTIVE: To evaluate the effects of daily low-dose follicular-phase cocaine
      administration on menstrual cyclicity, ovulation rates, corpus luteum function,
      and hormone levels in rhesus monkeys. METHOD: Normally cycling, drug-naive, adult
      rhesus monkeys were randomized to receive either 1 mg/kg of cocaine (n = 7), 2
      mg/kg of cocaine (n = 7), or normal saline (n = 7) daily on cycle days 2 to 14.
      Daily blood samples were obtained through indwelling catheters for measurement of
      serum gonadotropins and ovarian steroids. Daily vaginal swabs were obtained to
      determine onset of menses. Laparoscopy was performed 2 days after the midcycle
      estrogen peak to document ovulation. Daily caloric intakes as well as
      pretreatment and posttreatment weights were recorded. RESULTS: Two of seven
      monkeys receiving 1 mg/kg per day and two of seven monkeys receiving 2 mg/kg per
      day of cocaine had timely ovulation and normal menstrual cycle lengths. One
      monkey receiving the 2-mg/kg dose ovulated on cycle day 24 and had a short luteal
      phase (7 days) with a mean progesterone level of 2.4 ng/mL. All seven saline
      treated control monkeys ovulated normally; the mean cycle length was 29 days and
      all had adequate luteal phases. The difference in ovulation rates between cocaine
      treated and control monkeys was statistically significant (P = .003). There were
      no differences in basal levels of LH or FSH between treatment groups. There were
      no significant differences in weight change or caloric intake among groups. One
      third of the subsequent menstrual cycles in cocaine-treated monkeys were of
      abnormal duration. CONCLUSION: Daily low-dose follicular-phase cocaine
      administration disrupts menstrual cyclicity and folliculogenesis. This effect is
      independent of weight loss, caloric intake, and basal gonadotropin levels.
      Cocaine exposure may have a persistent effect on menstrual and ovarian cyclicity
      in some monkeys.

PMID- 10205780
TI  - Inhibitors of nitric oxide synthase influence oocyte maturation in rats.
AB  - OBJECTIVE: To examine the effect of inhibiting nitric oxide synthase (NOS) on the
      number of ovulated oocytes and on oocyte meiotic maturation. METHODS: Female
      Sprague-Dawley rats (25 days old) were superovulated with a subcutaneous
      injection of 10 U pregnant mare's serum gonadotropin, followed 52 hours later by
      a subcutaneous injection of 10 U human chorionic gonadotropin (hCG). Three hours
      before and 3 hours after hCG injection, the rats were treated orally with the
      vehicle (0.5% methylcellulose) as the control or with either of two NOS
      inhibitors, N omega-nitro-L-arginine methyl ester (L-NAME) and L-N6-(1
      iminoethyl)-lysine (L-NIL). The rats were killed 20 hours after hCG injection,
      and oocytes present in the oviduct were flushed, counted, and classified for
      stages of meiosis. In addition, ovarian oocytes (12 hours post-hCG) and ovulated
      oocytes were treated with an immunofluorescent stain for the presence of
      endothelial NOS (eNOS). RESULTS: Strong positive staining for eNOS was observed
      in the cytoplasm of ovarian and ovulated oocytes. Control rats ovulated an
      average 43.0 +/- 4.1 oocytes each, which was lowered with either L-NAME or L-NIL
      (23.8 +/- 4.3 and 23.5 +/- 4.0 oocytes per rat, respectively; P < .002). We
      observed that significantly fewer ovulated oocytes obtained from rats treated
      with NOS inhibitors were at metaphase II (P < .006), the normal stage of meiosis
      for unfertilized oocytes, and a significantly greater percentage of oocytes
      displayed atypical morphology as compared with control oocytes (P < .0001).
      CONCLUSION: Ovarian nitric oxide synthesis is required for maximal ovulation, and
      a lack of nitric oxide during the periovulatory period results in severe defects
      in oocyte maturation.

PMID- 10205781
TI  - Cyclin D1 overexpression and p53 mutation status in epithelial ovarian cancer.
AB  - OBJECTIVE: To examine the cyclin D1 mRNA expression level in ovarian tumor
      samples as compared with normal ovaries and to determine the relationship between
      cyclin D1 overexpression and p53 mutation status in ovarian tumors. METHODS: mRNA
      was isolated and cDNA was prepared from 27 epithelial ovarian tumors (3 tumors of
      low malignant potential (LMP) and 24 cancers) and 6 normal ovaries. The cyclin D1
      sequences were amplified by using a thermal cycler in parallel with the beta
      tubulin gene as an internal control. The cyclin D1 mRNA expression level relative
      to beta-tubulin was determined by 32P phosphoimager analysis. To confirm the
      overexpression of the cyclin D1 protein in ovarian tumor cells, immunostaining
      was performed. The p53 gene mutation status was examined by direct cDNA
      sequencing. RESULTS: mRNA levels of cyclin D1 were significantly higher in 21
      (78%) of the 27 ovarian tumors than in normal ovaries. Cyclin D1 overexpression
      was detected in ovarian LMP tumors as well as in ovarian cancer cases. Positive
      immunostaining of cyclin D1 protein was observed in 10 of 18 (56%) ovarian tumors
      examined. p53 mutations were found in 11 (61%) of 18 ovarian tumors. Of 11
      ovarian tumor cases with p53 mutations, 5 showed overexpression of cyclin D1. All
      7 ovarian tumor cases without p53 mutations showed significant cyclin D1 mRNA
      overexpression. CONCLUSION: Cyclin D1 overexpression seems to be an early genetic
      event in ovarian tumor development. Although p53 may be one of the proteins whose
      function regulates the expression of G1 cyclins, ovarian tumors with no p53
      mutation consistently showed cyclin D1 overexpression. Cyclin D1 overexpression
      may play an important role in the tumorigenesis of epithelial ovarian tumors.

PMID- 10205782
TI  - [Metabotropic glutamate receptor: its ligands and function in the olfactory
      system].
AB  - The metabotropic glutamate receptors (mGluRs) consist of at least eight different
      subtypes. However, the lack of specific ligands for this class of receptors
      limited the characterization of their roles. In this study, a series of glutamate
      derivatives was systematically tested for agonist and antagonist activities for
      the mGluR subtypes, individually expressed in cell lines. Among various compounds
      tested, (2S, 1'R, 2'R, 3'R)-2-(2,3-dicarboxycyclopropyl) glycine (DCG-IV) was
      found to be an effective agonist for mGluR2 and alpha-methyl-4
      carboxyphenylglycine (alpha M4CPG) was found to be an antagonist for both mGluR1
      and mGluR2. Using DCG-IV, I showed that mGluR2 mediates presynaptic inhibition of
      GABA release from granule cells at the dendrodendritic synapse of the accessory
      olfactory bulb (AOB). This mechanism was considered to relieve a mitral cell from
      GABAergic inhibition and, furthermore, to be involved in lateral inhibition of
      surrounding mitral cells and thus enhancing the signal/noise ratio of olfactory
      sensation. I also show that an activation of mGluR2 in AOB by infusion of DCG-IV
      induces olfactory memory, which can mimic the pregnancy block phenomenon of
      female mice. This is the first report of a role of specific subtype of mGluR in
      the central nervous system.

PMID- 10205783
TI  - [Availability of 2VO rats as a model for chronic cerebrovascular disease].
AB  - We have established a chronic cerebral hypoperfusion model that is produced by
      permanent occlusion of bilateral common carotid arteries (2VO) in rats. 2VO rats
      exhibited rarefaction in the white matter, shrinkage of neurons in the cerebral
      cortex and hippocampus 1-3 days after 2VO and infarctions in the striatum 7 days
      after 2VO. These histological changes in the cortex and hippocampus were
      accompanied by a decrease in immunoreactivity for microtubule-associated protein
      2 (MAP2). Immunoreactivity for glial fibrillary acid protein (GFAP) was observed
      at 3-7 days after 2VO. Marked increase in GFAP staining in astrocytes in the
      cerebral cortex and hippocampus was found 30 days after ligation. In the 8-arm
      radial maze performance, the 2VO rats showed a higher rate of errors than the
      sham-operated control during repeated training periods. THA (9-amino-1,2,3,4
      tetrahydroacridine), a cholinesterase inhibitor and GTS-21 (3-(2,4
      dimethoxybenzylidene)-anabaseine dihydrochloride), a central nicotinic
      acetylcholine-receptor agonist improved the learning impairment in the radical
      maze task of 2VO rats. GTS-21 administration exerted a protective effect against
      the neuropathological changes that followed 2VO. Taken together, the 2VO rat
      appears to be a useful model for investigating the pathophysiology of human
      dementia and to elucidate the therapeutic potential of drugs for this disease.

PMID- 10205784
TI  - [Involvement of caspase on apoptosis in ischemia-induced neuronal cell death:
      usefulness of caspase inhibitors for stroke therapy].
AB  - This overviews recent understanding of the mechanisms of apoptosis on ischemia
      induced neuronal cell death. Apoptosis is a prominent feature of the developing
      nervous system. Several lines of evidence suggest that apoptosis is also an
      important mechanism of cell death in adult brain in acute or chronic diseases
      such as stroke and Alzheimer's disease. In animal models of stroke, markers of
      apoptosis such as cytoplasmic and nuclear condensation and DNA fragmentation
      appear in neurons. A variety of physiological and pathological stimuli can
      activate signal-transduction pathways that result in the sequential proteolytic
      activation of caspase family members. The activation of caspases can be inhibited
      by several molecules, including peptide aldehydes (caspase-1 and or caspase-3
      inhibitors) and crmA that target the active-site cysteine of caspase family
      members, Bcl-2, IAP (inhibitor of apoptosis protein) and NAIP (neuronal apoptosis
      inhibitory protein). Once activated, caspase-1 protease can activate the caspase
      family members and hydrolyze a discrete set of cellular targets. Poly (ADP
      ribose)polymerase (PARP), which appears to facilitate apoptosis, was recognized
      as a substrate of activated caspase-3. These results suggest that caspase family,
      bcl-2 family, IAP family and substrates such PARP contribute to mechanisms of
      cell death in ischemic brain injury. Inhibition of the caspase family,
      particularly by non-peptide inhibitors that cross the blood-brain barrier and
      easily penetrate neurons and glia, could provide novel treatments for stroke and
      other forms of brain and spinal cord injury in humans.

PMID- 10205785
TI  - [The psychological stress model using motor suppression].
AB  - Psychological stress is believed to be implicated in the etiology of affective
      disorders such as anxiety and depression. To date, a wide range of behavioral
      responses including analgesia and motor suppression induced by various
      physiological stressors such as footshock, forced swimming and immobilization
      have been investigated in animals. However, there is little information
      concerning behavioral changes in psychological stress. This article describes the
      experimental procedures and the characteristics of motor suppression in
      psychological stress, defined as conditioned fear stress (CFS). Mice exhibit a
      marked suppression of motility when they are re-placed in the same environment in
      which they had previously received an electric footshock. This motor suppression
      is regarded as a conditioned emotional response to the environment associated
      with previous footshock. The motor suppression in CFS is attenuated by sigma
      receptor agonists such as (+)-N-allylnormetazocine and dextromethorphan, whereas
      typical anxiolytics (diazepam and chlordiazepoxide) and antidepressants
      (imipramine and fluoxetine) have no effect. These findings suggest that the CFS
      model may be useful for investigating the pathogenesis of affective disorders,
      particularly those considered to be treatment resistant, and for developing their
      novel therapeutic drugs.

PMID- 10205786
TI  - [Experimental research on the cellular interactions during hemopoiesis].
AB  - We present a review of experimental studies performed at the Laboratory of
      Histogenesis of the Institute of Developmental Biology, Russian Academy of
      Sciences, on the problem of cell interactions during hemopoiesis. Special
      attention has been given to original experimental models, such as production of
      hemopoietic foci on underlayers of fibroblasts encapsulating a foreign body in
      the peritoneal cavity of rodents (after intraperitoneal transplantation of
      hemopoietic cells) and repopulation of ectopic hemopoietic territories under the
      kidney capsule of mice by syngeneic or xenogeneic hemopoietic cells. We describe
      the competitive interactions of genetically different hemopoietic cells after the
      transplantation of their mixtures to irradiated mice (multicomponent radiation
      chimeras). Xenogeneic and multicomponent chimeras have also been obtained in long
      term bone marrow culture. We have examined characteristics of hemopoiesis on
      stromal cell underlayers produced by cells of various origins in vitro and then
      transplanted into the peritoneal cavity of irradiated mice. We discuss the
      results obtained and possible mechanisms of these phenomena.

PMID- 10205787
TI  - [A comparative study of the transport dynamics of the peptide moiety of the milk
      ceruloplasmin molecule in the body of rats with embryonic and adult types of
      copper metabolism].
AB  - In chase experiments, we followed the distribution of [125I]-ceruloplasmin
      prepared from human breast milk orally administered to young rats. Experiments
      were conducted using six-day-old rat pups (the embryonic type of copper
      metabolism) or 35-day-old ones (the adult type of copper metabolism). Using the
      technique of rocket immunoelectrophoresis, we have demonstrated that in six-day
      old rats [125I]-ceruloplasmin was transferred from the gastrointestinal tract to
      the bloodstream and could be detected there over a period of 4 h. In 35-day-old
      rats, milk ceruloplasmin was digested in the upper part of the intestinal tract.
      The dynamic aspects of the distribution of labeled milk ceruloplasmin in the body
      of six-day old rats over a period of 4 h point out that, under the conditions of
      embryonic copper metabolism, it can serve as a transporter of copper ions to
      extrahepatic organs. We discuss the role of milk ceruloplasmin in copper
      metabolism in mammals during the neonatal period.

PMID- 10205788
TI  - [The morphogenesis of layer I of the mouse cerebral cortex in the prenatal
      developmental period].
AB  - Cajal-Retzius (CR) cells begin to differentiate in mice at day 10 of embryonic
      development. At days 11 and 12, the subpial zone becomes visible, as well as the
      cell population, which will comprise the plexiform layer, which appears at day
      13. All cell types characteristic of layer I appear at day 14. We have described
      a characteristic feature of neurogenesis of layer I, i.e., found that the
      appearance of its cell elements proceeds in two phases: the first peak
      corresponds to early postimplantation development, whereas the second peak begins
      from day 14 of development and continues to the end of the fetal period.

PMID- 10205789
TI  - [The observation of partial regeneration of the tip of tail in newborn rat pups
      in a liquid medium].
AB  - When the wound surface formed as a result of amputation of the tail tip in
      newborn rats was placed in sterile 0.9% aqueous solution of sodium chloride until
      full epithelialization of the defect, the epithelium moved onto the blood clot
      covering the wound. The blood clot was then substituted for connective tissue,
      into which the traumatized vertebra protruded. The vertebra restored its
      anatomical integrity, and this led to partial regrowth of the tail. A skin
      regenerate was formed on the apical tail surface with characteristic features of
      the intact skin of this locality. In the control animals, no regeneration of the
      vertebra epiphysis took place and a scar was formed at the stump end.

PMID- 10205790
TI  - [The effect of overfeeding the young in early postnatal ontogeny on brown fatty
      tissue].
AB  - We studied the effects of overfeeding of neonatal Wistar rats on O2 consumption
      by the interscapular brown adipose tissue and DNA content in the tissue. The
      overfeeding was induced by reducing the litter size to two to three pups per dam
      compared with standard litters of five to ten pups. All animals were allowed free
      access to water and forage and were kept at 24 +/- 1 degrees C. Newborn and 16
      day-old rat pups were used in the experiments. The body weight of overfed pups
      was significantly higher than that of standard fed pups (p < 0.001). There were
      no differences between groups of 16-day-old rats in the resting metabolic rate.
      The mass of dried brown adipose tissue relative to the body mass in overfed pups
      was lower than in the control pups (p < 0.01). O2 consumption in the rats from
      small litters was 35% higher (p < 0.001). DNA content (mg/g brown adipose tissue)
      in overfed rats was 35% lower as compared to the control pups (p < 0.001). These
      results indicate that overfeeding at the preweaning stage of life affects growth,
      cellularity, and thermogenic function of brown adipose tissue.

PMID- 10205791
TI  - [An analysis of parthogenetic cell clones in chimeric C57BL/6(PG)<-->BALB/c
      mice].
AB  - We studied the distribution of parthenogenetic cell clones in the retinal pigment
      epithelium and choroid of eyes on serial sections and in the brain, kidneys, and
      liver by electrophoretic analysis of glucose phosphate isomerase isozymes in 12
      mouse chimeras C57BL/6(PG)<-->BALB/c obtained earlier. Asymmetry was noted in the
      distribution of the parthenogenetic cell clones in the eye structure, just as the
      earlier established asymmetry in the distribution of the parthenogenetic clones
      of epidermal melanoblasts. A high correlation was shown between the ratio of
      parthenogenetic to normal cells in the retinal pigment epithelium of the right or
      left eyes and epidermal melanoblasts in the hair cover of the corresponding body
      half of the chimera. These data suggest that there is a certain relationship
      between the processes leading to the characteristic distribution of the
      ectodermal parthenogenetic clones in the retinal pigment epithelium of the right
      and left eyes and epidermal melanoblasts in parthenogenetic chimeras.
      Electrophoretic analysis did not show parthenogenetic components in the liver or
      kidneys of any chimera, and the parthenogenetic component was found in the brain
      of only two chimeras, in which a high percentage of parthenogenetic cells of
      ectodermal origin was noted. In these cases, asymmetry was noted in the right and
      left cerebral hemispheres, just as in the retinal pigment epithelium of the right
      and left eyes. The data obtained suggest that, during the development of the
      chimeras, parthenogenetic C57BL/6 cells were actively eliminated from the tissues
      of endodermal and mesodermal origin. In adult chimeras C57BL/6(PG)<-->BALB/c,
      parthenogenetic cell clones of ectodermal origin are mostly preserved.

PMID- 10205792
TI  - Innate resistance to experimental Trypanosoma congolense infection: differences
      in IL-10 synthesis by macrophage cell lines from resistant and susceptible inbred
      mice.
AB  - BALB/c and C57Bl/6 mice differ in resistance to T. congolense infections. We
      investigated the production of various cytokines (IL-10, IL-6, TNF-alpha and TGF
      beta) by macrophages from these mice. Macrophage cell lines (BALB.BM cells) of
      BALB/c mice but not (ANA-I cells)of C57BL/6 mice constitutively produced IL-10.
      Challenge of these cells with trypanosomes induced the production of 50-100 times
      more IL-10 in BALB.BM cells than in ANA-1 cells. Pre-incubation of the cell lines
      with IFN-gamma. prior to the trypanosome challenge, further upregulated this IL
      10 production in BALB.BM but not in ANA-1 cells. Primary cultures of bone marrow
      derived macrophages (BMDM) from BALB/c mice also produced more IL-10 following
      challenge with IFN-gamma and opsonized trypanosomes than did the C57Bl/6 BMDM.
      Similarly after challenge with trypanosomes, BALB.BM and BALB/c BMDM produced
      significantly more IL-6 than did the analogous cells from the C57Bl/6 mice
      following such challenges. Higher steady state levels of TNF-alpha mRNA
      accumulated in ANA-1 cells than in BALB.BM cells following challenge with IFN
      gamma and opsonized trypanosomes. Findings of this study for the first time
      indicate a differential regulation of cytokines (IL-10, IL-6 and TNF-alpha) in
      macrophages of mice that significantly differ in their susceptibility to
      infections with T. congolense.

PMID- 10205793
TI  - Human antibodies to the 19kDa C-terminal fragment of Plasmodium falciparum
      merozoite surface protein 1 inhibit parasite growth in vitro.
AB  - The 19kDa, C-terminal fragment of the major surface protein of Plasmodium
      falciparum (PfMSP1(19)) is a candidate for inclusion in a subunit malaria
      vaccine. In this study, we show that PfMSP1(19)-specific antibodies, affinity
      purified from malaria-immune human serum, can: (i) compete with invasion
      inhibitory monoclonal antibodies for binding to PfMSP1(19) and (ii) mediate
      inhibition of parasite growth in vitro, in the absence of complement and
      mononuclear cells, at physiological antibody concentrations (100 micrograms/ml).
      Parasites expressing either the Kl or 3D7 allele of PfMSP1(19) were equally
      susceptible to inhibition of merozoite invasion, indicating that the target
      epitopes of inhibitory antibodies are conserved or cross-reactive. These studies
      suggest that vaccines designed to induce antibodies to PfMSP1(19) may protect
      against the high levels of malaria parasitaemia which are associated with
      clinical disease.

PMID- 10205794
TI  - Antibody response in CD4-depleted mice after immunization or during early
      infection with Echinococcus granulosus.
AB  - The aims of this work were to investigate the existence of T-independent antigens
      in Echinococcus granulosus protoscoleces and to evaluate the relative
      contribution of T-independent stimulation to the overall antibody response in
      early infection. Mice depleted of CD4(+)-cells were immunized with protoscolex
      somatic antigens (PSA) or infected with E. granulosus protoscoleces (PSC).
      Results showed that the response of CD4-depleted immunized mice had the expected
      characteristics of a T-independent stimulation and that such T-independent
      stimulation was important mainly during primary response. During infection
      absence of CD4(+)-cells affected mainly the secretion of all IgG subclasses with
      the exception of IgG3 and IgM. To carry out a preliminary isolation of PSC T
      independent antigens we prepared a carbohydrate enriched fraction from
      protoscolex antigens, using a monoclonal antibody specific for the carbohydrate
      moiety Gal alpha(1,4)Gal highly expressed in PSC. This fraction was mitogenic for
      naive mouse splenocytes and was recognized by a high percentage of the specific
      antibodies secreted by CD4-depleted immunized or infected mice. In summary, these
      results suggest that E. granulosus protoscoleces contain immunogenic T
      independent antigens. Primary antibody responses to protoscolex somatic antigens
      and the production of IgM and IgG3 in early infection would be mainly stimulated
      by a T-independent mechanism.

PMID- 10205795
TI  - Mucosal mast cell responses and release of mast cell protease-I in infections of
      mice with Hymenolepis diminuta and H. microstoma: modulation by cyclosporin A.
AB  - The dynamics of intestinal mucosal mast cells and the major mucosal mast cell
      protease were followed during the course of laboratory infections of mice with
      Hymenolepis diminuta and H. microstoma. The effects of the drug cyclosporin A
      (CsA), which is both immunosuppressive and selectively anthelmintic depending
      upon dose regime, were determined. In H. diminuta infections worm expulsion
      occurred around day 9 and coincided with peak mastocytosis and peak mMCP-I
      concentrations in tissues and serum. Immunosuppressive treatment with CsA
      prevented worm expulsion, permitting some individuals to reach maturity, and
      abrogated mast cell proliferation and mMCP-I production and release. By contrast,
      H. microstoma infections persisted for 64 days in spite of a considerable
      mastocyosis in both intestine and bile duct tissues accompanied by a high level
      of mMCP-I in tissues and serum. A subimmunosuppressive regime of CsA had only
      limited effects on worms and mast cell numbers and activity. Together these data
      shed light on the variable mast cell response to gastrointestinal infections and
      on the potential significance of parasite location in evasion of mast cell
      action. Use of CsA reveals the contributions of both T cell-dependent mechanisms,
      including mast cell proliferation and activation, and T cell-independent events
      in regulating intestinal helminth infections.

PMID- 10205796
TI  - The recognition of molecules from fourth-stage larvae of Ostertagia circumcincta
      by IgA from infected sheep.
AB  - The recognition of antigens from fourth-stage Ostertagia circumcincta by plasma
      IgA was studied in a group of 30, ten-month-old Scottish Blackface sheep which
      had been naturally, then deliberately infected. Western blotting revealed 49
      bands that were recognized by antibody from one or more of the 30 sheep. There
      was a heterogeneous pattern of antigen recognition amongst the sheep. No
      individual recognized all the 49 bands and only one of the 49 bands was
      recognized by all sheep. Two antigens with approximate molecular weights 87,000
      Da and 129,000 Da were significantly associated with a reduction in mean adult
      worm lengths. The observed variation in recognition of these two antigens on
      fourth-stage larval preparations accounted, in a statistical sense, for nearly
      40% of the total variation in worm length. In addition to the variation in
      antibody mediated recognition of these two parasite molecules, three other
      components have been implicated in regulating worm length. They are a 37,000 Da
      band from adult worms, the amount of fourth-stage larval specific IgA in the
      abomasal mucosa and the density-dependent influence of adult worm burden.
      Together, these components and their interactions accounted for over 90% of the
      observed variation in worm length. These results indicate that the parasite
      specific IgA response, or something extremely closely associated with it, is the
      major immunological mechanism controlling worm length.

PMID- 10205797
TI  - Irradiated sporozoites prime mice to produce high antibody titres upon viable
      Plasmodium berghei sporozoite challenge, which act upon liver-stage development.
AB  - C57BL6 mice were protected against Plasmodium berghei sporozoite challenge by
      immunization with live 12 krad dose-irradiated sporozoites, but not by 20 krad
      dose-irradiated sporozoites. Immunization with 12 krad irradiated sporozoites
      generated low levels of antibody reactive to liver-stage parasites (titres of
      1/100). Inoculation of as few as 100 live P. berghei sporozoites induced complete
      host protection accompanied by a very quick and high boost of antibody titres up
      to 1/4000. This sporozoite challenge-drive antibody boost was absent in mice
      immunized by 20 krad sporozoites and in non-protected, and non-immunized mice.
      Antibody was mainly liver-stage (LS) specific and due to an increase of IgG2a and
      IgG2b. The in vitro effect of pre- and post-challenge sera upon either sporozoite
      invasion or LS development was assessed in Hep-G2 cultures. Both were found to
      have a strong effect upon LS development even at 1/2500 dilution, and conversely
      a low effect upon invasion. These results suggest that sporozoites irradiated at
      doses that induce protection are able to prime T-cells which, upon challenge by
      non-irradiated sporozoites, provide help to B-lymphocytes to trigger the
      production of high titres of anti-LS antibodies that can inhibit LS development
      in vitro.

PMID- 10205798
TI  - Development of Sarcocystis falcatula in cell cultures demonstrates that it is
      different from Sarcocystis neurona.
AB  - The development of Sarcocystis falcatula merozoites in bovine turbinate (BT) cell
      cultures is described and compared with development of Sarcocystis neurona
      merozoites. Merozoites of S. falcatula entered BT cell cultures and increased in
      size until 3 days post-inoculation when the nucleus of some merozoites developed
      lobes. Developing schizonts present at 4 days contained a lobed nucleus or
      appeared multinucleate. A single mature schizont was observed 4 days p.i.
      Schizonts were numerous 5 and 6 days p.i. Merozoites were produced from
      blastophores on the schizont. S. neurona merozoites developed to mature schizonts
      by 3 days p.i. in BT cells and a residual body was often present. Transmission
      electron microscopy revealed that S. falcatula merozoites possessed more
      micronemes than did S. neurona merozoites. Our study demonstrates that S.
      falcatula and S. neurona are not the same parasite.

PMID- 10205799
TI  - Identification of a subpopulation of merozoites of Sarcocystis singaporensis that
      invades and partially develops inside muscle cells in vitro.
AB  - The affinity of merozoites of Sarcocystis singaporensis obtained from the lungs
      of acutely infected rats to muscle cells and other cell lines grown in vitro was
      examined. Two distinct types of mature schizonts developed in the lungs 11-13
      days p.i. with sporocysts: those containing PAS- merozoites (type 1) which mainly
      reacted with antibodies prepared against sporozoites, and others containing PAS+
      merozoites (type 2) which were antigenically close to bradyzoites. When
      inoculated onto cell cultures, type 1-merozoites induced schizogonic development
      in brain capillary endothelial cells of the rat. In contrast, type 2-merozoites
      invaded L6 myoblasts. In long-term cultures (50 days) of L6 cells, zoites
      transformed to a 8-15 microns long uninucleate stage which, tentatively, could be
      unizoite sarcocysts. Although the observed dichotomy in merozoite development is
      unprecedented in this form, evidence from previous work suggests that these
      observations are relevant to other Sarcocystis species. The presented cell
      culture system could be a first step towards successful growth of sarcocysts in
      vitro.

PMID- 10205800
TI  - Glomerular disease associated with Polysporoplasma sparis (Myxozoa) infections in
      cultured gilthead sea bream, Sparus aurata L. (Pisces: Teleostei).
AB  - Polysporoplasma sparis infection was studied in gilthead sea bream from different
      mariculture systems of the Spanish coasts. Culture conditions influenced the
      infection dynamics, as the parasite appeared only in semi-intensive cultures and
      was not found in intensive closed systems nor in open ones. No clear seasonal
      pattern was observed. No fish weighing less than 51 g was found parasitized in
      any group. A statistically significant dependence between infection prevalence
      and host weight was observed in some growing stocks. Light and transmission
      electron microscope observations revealed serious damage in the trunk kidney.
      Glomerular disease was provoked by the progressive occupation of the glomerular
      capillaries by P. sparis spores. Tubular epithelial cells were also affected.
      Inflammatory responses appeared towards the end of the infection, and consisted
      mainly of melanomacrophages and eosinophils. Rodlet cells were common close to
      infected capillaries and debris of rodlet sacs formed a belt encircling capillary
      vessels. Cytochemistry demonstrated the lipidic nature of these sacs and the
      glycogen and glycoprotein composition of the cytoplasmic granules of rodlet
      cells.

PMID- 10205801
TI  - Can prevalence of infection in school-aged children be used as an index for
      assessing community prevalence?
AB  - Community data on the prevalence of helminth infections is important for guiding
      health policy, but expensive to collect. As a result most surveys focus on school
      aged children, frequently using schools as a sentinel population. Since there
      already exists a vast amount of data on infection levels in school-aged children,
      but limited community-based data, we undertook a literature search on age
      stratified infection data for intestinal nematode infections and schistosomiasis
      in Africa, to investigate whether estimates of the prevalence of infection in
      school-aged children could provide an index for determining community prevalence.
      The observed data on prevalence of infection in infants, school-aged children and
      adults were fitted using linear and logistic regression models which take into
      account variation in sample prevalences. Despite the wide variation in study
      sites, the observed relationship between community prevalence and school-aged
      prevalence was remarkably consistent for each parasite species. The prevalence of
      infection in school-aged children alone was shown to be higher than the predicted
      prevalence in the community, but the degree of overestimation was dependent on
      the parasite species and the level of infection. The results suggest that the
      prevalence of infection in school-aged children could provide a cost-effective
      predictive tool which can be used at a district/national level to identify target
      areas for control and to evaluate the numbers at risk of infection.

PMID- 10205802
TI  - Characteristics of eosinophilic inclusions within Schistosoma japonicum eggs.
AB  - Although eosinophilic bar- or droplet-like inclusions are frequently detectable
      inside eggs deposited in the livers of Schistosoma japonicum-infected animals,
      little is known of their exact nature. In the livers of mice implanted with
      freshly laid eggs, inclusion-positive eggs were found in 28.7 and 46.2% of
      deposited eggs at 2 and 4 weeks, respectively, after implantation, but in 4.3% at
      5 weeks when most of the eggs had already degenerated. When the extent of
      granuloma formation was investigated, granulomas around inclusion-positive eggs
      were smaller than those around negative eggs. Host factors associated with the
      formation of inclusion were sought using in vivo and in vitro studies. Following
      the administration of anti-egg antigen serum into egg-implanted mice, no increase
      in occurrence of inclusion-positive eggs was seen. In a co-culture of mature eggs
      with infected rabbit or mouse serum, inclusions were rarely found. In contrast,
      they were found in 17.9% of eggs in the presence of splenic cells. The present
      study is the first to show that there is decreased granuloma formation in the
      presence of eosinophilic inclusions inside eggs and our in vitro study suggests
      that host cell-egg interaction is responsible for the formation of inclusions.

PMID- 10205803
TI  - Dipeptidyl peptidase I and III activities of adult schistosomes.
AB  - Soluble extracts of adult Schistosoma japonicum and S. mansoni were examined for
      the presence of proteolytic activities ascribable to dipeptidyl peptidases (DPPs)
      at a range of pH from 4 to 11 using synthetic peptidyl substrates diagnostic of
      DPPs I, II, III and IV. Activity capable of cleaving the DPP I-specific
      substrates H-Gly-Arg-NHMec and H-Gly-Phe-NHMec which exhibited a pH optimum of
      5.5 was observed in extracts of schistosomes. Female schistosomes exhibited
      greater DPP I activity than male schistosomes, while female S. japonicum showed
      substantially more activity than female S. mansoni. The specific activities
      against H-Gly-Arg-NHMec were 21.5 and 1.9 nmoles NHMec/min/mg protein for female
      and male S. japonicum and 8.5 and 1.9 nmoles NHMec/min/mg for female and male S.
      mansoni. The biochemical properties of schistosome DPP I were similar to
      mammalian DPP I (= cathepsin C) in that schistosome DPP I was only slowly
      inhibited by the cysteine protease inhibitor trans-epoxysuccinyl-1-leucylamido (4
      guanidino)-butane, partly inhibited by the blocked diazomethyl ketones Z-Phe-Ala
      CHN2 and Z-Phe-Phe-CHN2, but enhanced by halide ions. At pH 8.5, activity against
      the DPP III-specific substrate H-Arg-Arg-NHMec was evident in schistosome
      extracts, and this activity appeared to be due to a zinc metallo-exopeptidase
      because it was inhibited by 1,10-phenathroline and by EDTA. DPP II or DPP IV
      activity was not detected in the schistosome extracts.

PMID- 10205804
TI  - Diagnosis of Oesophagostomum bifurcum and hookworm infection in humans: day-to
      day and within-specimen variation of larval counts.
AB  - Oesophagostomum bifurcum, as well as hookworm infections are hyperendemic among
      humans in northern Togo and Ghana. For parasite-specific diagnosis a coproculture
      is obligatory, because only the infective larvae, and not the eggs, can be
      distinguished morphologically. The sensitivity of duplicate coprocultures from a
      single stool sample was found to be above 90% in comparison to a gold standard of
      10 coprocultures made from a single stool specimen. Prevalence of infection with
      O. bifurcum and hookworm further increased with the number of coprocultures made
      from each individual stool. Notwithstanding the high sensitivity, intensity of
      infection per individual varied considerably from day-to-day and the number of
      larvae found in different samples out of 1 stool also varied highly, both showing
      a heterogeneous distribution. Surprisingly, daily fluctuation and within-specimen
      variation could not be differentiated from each other, probably because of the
      variation created by the coproculture technique. To estimate the intensity of
      infection, it is sufficient to make repeated coprocultures from only 1 individual
      stool sample. Laborious collection of stool samples on subsequent days does not
      give better estimates of the individual infection status.

PMID- 10205805
TI  - Density-dependent effects on Anguillicola crassus (Nematoda) within its European
      eel definitive host.
AB  - Density-dependent effects on adult and larval stages of the introduced nematode
      parasite Anguillicola crassus in the European eel definitive host were examined
      in the laboratory in naturally infected fish, and in field samples. The effect of
      adult nematode subpopulations on larval development over time and the effect of
      increasing adult intensity on the gravid female subpopulations were investigated.
      At high adult subpopulations the movement of larvae from the swimbladder wall
      into the swimbladder lumen appears to be inhibited, and A. crassus larvae to be
      arrested in development in a density-dependent manner. The number of gravid
      females per host reaches a constant level, and so the proportion of gravid female
      nematodes per adult subpopulation decreases relative to further increasing total
      adult nematode numbers. Both these mechanisms have the potential to regulate
      infrapopulations of A. crassus within the eel definitive host and thus the
      parasite suprapopulation.

PMID- 10205806
TI  - Cloning and characterization of glutamate dehydrogenase (GDH) from the gut of
      Haemonchus contortus.
AB  - Vaccination of lambs with the membrane-bound (S3) thiol-Sepharose binding protein
      (TSBP) fraction derived from the gut of Haemonchus contortus confers significant
      protection against homologous challenge. The S3 TSBP peptide profile is dominated
      by a major protein of ca. 60 kDa which is strongly recognized by antisera from
      sheep demonstrably protected following immunization with S3 TSBP. In an attempt
      to identify this protein, sera from protected lambs were employed to screen a
      lambda gt11 cDNA library of the adult parasite and resulted in the isolation of
      numerous clones encoding a homologue of the mitochondrial enzyme, glutamate
      dehydrogenase (GDH). GDH enzyme activity was readily demonstrable in S3 TSBP
      material and immunolocalization studies showed that the enzyme was localized to
      the cytoplasm of the parasite's gut. Furthermore, the enzyme appeared to be
      developmentally regulated, with both GDH mRNA and protein expressed almost
      exclusively during the blood-feeding parasitic stages.

PMID- 10205807
TI  - Effects of an Onchocerca-derived cysteine protease inhibitor on microfilariae in
      their simuliid vector.
AB  - A recombinant cysteine protease inhibitor, onchocystatin of the parasitic
      nematode Onchocerca volvulus, was tested for its role in microfilarial
      development in the simuliid vector. Onchocystatin was found to be present in
      female adults and skin microfilariae of the bovine parasite O. ochengi, the
      closest relative of O. volvulus. In addition the inhibitor could be detected as
      an excretory-secretory (E-S) product of the microfilariae. Co-injection of
      onchocystatin and the O. ochengi microfilariae into the surrogate vector Simulium
      ornatum s.l. significantly enhanced the recovery rates of the parasite within 24
      h into the infection (P > 0.001). The findings suggest a possible role of
      onchocystatin in the evasion by the parasite of the immune response of its
      vector.

PMID- 10205808
TI  - Mechanisms underlying the transfer of phosphorylcholine to filarial nematode
      glycoproteins--a possible role for choline kinase.
AB  - Phosphorylcholine (PC) is a common constituent of proteins secreted by filarial
      nematodes. As this substance has been shown to interfere with immune responses,
      we are interested in designing strategies for blocking its attachment. Towards
      this end, we are investigating the mechanism of incorporation of PC into filarial
      molecules and in the present manuscript we describe experiments relating to
      elucidating the source of PC for attachment. Synthesis of phosphatidylcholine in
      eukaryotic organisms can occur by a mechanism involving the transfer of PC from
      CDP-choline to diacylglycerol (the Kennedy pathway). By (i) measuring transfer of
      radio-isotope labelled PC from CDP-choline to parasite molecules and (ii)
      employing inhibitors of CDP-choline synthesis, we have investigated whether CDP
      choline can act as a source of PC for transfer to ES-62, a major secreted
      glycoprotein of the rodent filarial nematode Acanthocheilonema viteae. Although
      we can find no evidence of this, we show that attachment of PC is blocked by
      hemicholinium-3, an inhibitor of choline kinase, the first enzyme in the Kennedy
      pathway. Thus, at least the first step in this pathway--phosphorylation of
      choline, would appear to be necessary for attachment of PC to ES-62.

PMID- 10205809
TI  - Ultrastructural localization of an Echinococcus granulosus laminin-binding
      protein.
AB  - Murine antibodies, raised against a purified recombinant 30 kDa laminin-binding
      protein from Echinococcus granulosus, were used to investigate the tissue
      distribution of the native protein in protoscoleces and brood capsules.
      Immunofluorescence, in combination with confocal microscopy, revealed that the
      protein was distributed in small annular foci near the peripheral regions of the
      protoscoleces. Immunoelectron microscopy of thawed cryosections demonstrated that
      the laminin-binding protein was present in the cytoplasm of tegumentary cytons
      and myocytons, but not in cells of the excretory system. The protein was
      associated with amorphous regions of the cytoplasm, and was not expressed at the
      surfaces of cells. This distribution resembles those of other invertebrate
      laminin-binding proteins, which are thought to act in the cell cycle and cell
      proliferation events. A low degree of label was consistently detected in
      extracellular matrices of the protoscolex.

PMID- 10205810
TI  - Hyperbaric oxygen therapy: from the nineteenth to the twenty-first century.
AB  - Hyperbaric oxygen technology now occupies a legitimate place in modern medical
      practice, and the number of clinically active hyperbaric facilities has grown. We
      estimate that more than 200 monoplace (single-patient) chambers and over two
      dozen multiplace facilities are presently active in the United States.
      Nevertheless, the majority of patients suffering from syndromes amenable to HBO
      therapy are treated in hospitals devoid of such modalities. This situation stems
      in part from the significant cost of appropriate facilities, the relative
      scarcity of trained personnel, and the difficulties in obtaining appropriate
      compensation in an era of rapidly changing reimbursement paradigms. Frequently,
      patients undergoing HBO therapy require mechanical ventilation, vasoactive drug
      infusions, sophisticated monitoring, and accurate fluid and electrolyte therapy
      during treatment. The demonstrated efficacy of HBO as an important part of the
      treatment of certain acute disease processes, however, justifies the facilities
      and skilled personnel necessary for the care of critically ill patients in a
      hyperbaric environment.

PMID- 10205812
TI  - Operational use and patient monitoring in a multiplace hyperbaric chamber.
AB  - Multiplace hyperbaric chambers can be used to deliver patient care with enormous
      flexibility. Standard critical care techniques, such as mechanical ventilation,
      endotracheal suctioning, hemodynamic monitoring, blood gas measurement, and
      emergency therapy such as cardiopulmonary resuscitation, including defibrillation
      and cardioversion, can all be performed inside a multiplace chamber. The
      multiplace chamber can be considered an extension of the intensive care unit.
      This flexibility is accompanied by increased complexity of chamber operation.
      Careful attention must be paid to minimization of fire hazards and maintenance of
      a safe chamber atmosphere. Although life support apparatus can easily be taken
      inside the chamber and will usually work under hyperbaric conditions, care must
      be given to facilitate the benefits to the patient of hyperbaric oxygen treatment
      in the face of potential risks associated with rapid changes in environmental
      pressure and the partial pressures of the component gases.

PMID- 10205811
TI  - Physiology of hyperbaric hyperoxia.
AB  - This article reviews the essential physiology of oxygen exchange in the lungs,
      oxygen transport to tissue, and oxygen utilization by the body tissues. The
      physiologic effects of hyperbaric hyperoxia are summarized, with an emphasis on
      the circulatory responses to hyperoxia. Finally, the effects of hyperoxia on
      normal cellular processes are discussed.

PMID- 10205813
TI  - Operational use and patient care in the monoplace hyperbaric chamber.
AB  - The author has made an attempt to describe presently available monoplace
      chambers, provide codes for their appropriate use in hospitals, and emphasize
      chamber safety. If appropriate safety precautions are not strictly adhered to,
      catastrophic accidents may occur, and have occurred. Critically ill patients may
      have indications for HBO and, indeed, can be treated with HBO in the monoplace
      chamber. This requires strict attention to detail and an understanding of
      critical care medicine as well as hyperbaric medicine. To facilitate care of
      these patients within the monoplace chamber several modifications have been
      implemented. Complete pulmonary and arterial hemodynamic monitoring,
      transcutaneous and laser Doppler monitoring, as well as vasopressors, sedation,
      paralysis, and mechanical ventilation can be supplied to patients treated with
      HBO within a monoplace chamber (Fig. 19). Suction within the monoplace chamber
      can be accomplished by adapting existing hospital equipment. Likewise, air breaks
      can be provided to all patients in the monoplace chamber, including those who are
      intubated and mechanically ventilated. These modifications have been presented
      here. Hemodynamic and intravenous access to the critically ill patient is
      important. Physiologic pressures, ECG, and typical intravenous setups have been
      described. Several techniques that the author has have personally found helpful
      have also been provided. The final section of this article presents clinical
      observations in a few critically ill patients. These anecdotes were only included
      to try to stimulate thought and hopefully an interchange of ideas that may help
      us deal more effectively with the management of these patients. This article also
      raises the question of what is the optimal arterial partial pressure of oxygen as
      opposed to merely treating the HBO patient with a standard protocol, particularly
      if the patient has a significant right-to-left shunt (anatomic or physiologic).
      It is hoped that further discussion, thought, and research can help elucidate
      answers to these questions.

PMID- 10205814
TI  - Treatment of decompression illness and latrogenic gas embolism.
AB  - The mainstay of treatment of gas bubble disease is therapeutic recompression
      while the patient is breathing oxygen. The patient should be recompressed as soon
      as possible; however, patients should be considered for recompression even after
      several days' delay. Treatments should be repeated if possible until symptoms
      have either resolved or stabilized. Appropriate hydration is essential. The use
      of HBO is generally safe, relatively nontoxic, and is possible even in neonates.
      Pharmacologic agents (e.g., anticoagulants, lidocaine, antiplatelet agents,
      corticosteroids, inhibitors of calcium flux) may be useful adjuncts to
      recompression therapy but they require further study. For patients who respond
      poorly to recompression therapy, the next advance in the treatment of DCI-induced
      neural injury is likely to be due to the development of agents that reduce the
      effects of reperfusion injury and delayed cell death.

PMID- 10205815
TI  - Medical field management of the injured diver.
AB  - This article discusses the history of medical field management of the injured
      diver, and presents a comprehensive medical equipment list for field treatment as
      well as treatment protocols. Case reports are used to illustrate the principles
      and outcome of medical field management.

PMID- 10205816
TI  - [The peptide-dependent mechanisms of long-term posttetanic potentiation (the
      facts and a hypothesis)].
AB  - In the article literature data and results of our studying of long-term
      potentiation (LTP) are analyzed the position of the proposed hypothesis that
      cells secrete during their activation into extracellular space a neuromodulatory
      factors, affecting on cell population and promoting the transformation of short
      terms excitability in long-term one. It is considered the possible molecular
      messengers particulated in development LTP. The neurophysiological and
      neurochemical evidences of the involvement neuropeptides as the key retrograde
      messengers are presented. It is analyzed the biological assay method as the
      adequate approach for study the role of endogenous neuropeptide in the LTP and
      analogous models. The possible mechanisms acting of neuropeptide by cells in LTP
      genesis are discussed.

PMID- 10205817
TI  - [The molecular aspects of the functional heterogeneity of the GABA receptors].
AB  - It is generally accepted that gamma-aminobutyric acid (GABA) is one of the main
      inhibitory transmitter in the mammalian brain. There are three types of GABA
      receptors in the vertebrata central nervous system: the GABAA, GABAB and GABAC
      receptors. The GABAA receptor is a GABA-gated Cl- channel and is the tetramer ore
      the pentamer made of some classes of subunit (alpha, beta, gamma, delta). GABAB
      receptors are not affiliated with Cl(-) ionophore. GABAB receptors appear to be
      coupled to Ca2+ and K+ channels of presynaptic membranes. It seems they regulate
      the release of neurotransmitters release. The structural and functional
      properties of GABA receptors are discussed.

PMID- 10205818
TI  - [Antagonists of ionotropic glutamate receptors as the object of research in
      psychopharmacology].
AB  - Ionotropic glutamate receptors antagonists are now widely considered as potential
      medications for a variety of disorders, such as seizures, neurodegenerative
      diseases, stroke, and opiate tolerance and dependence. There is a growing body of
      evidence suggesting that the safest drugs are to be found amongst antagonists
      acting at glycine and polyamine sites of NMDA-receptor complex, low-affinity
      channel blockers, subtype-selective competitive NMDA-receptor antagonists, as
      well as non-NMDA glutamate receptors antagonists. These antagonists exhibit
      little or no abuse liability and are less likely to induce phencyclidine-like
      attention deficits and disruption of sensomotor gating. Meanwhile, these drugs
      retain most of the potentially useful properties, including anxiolytic and
      antidepressant effects.

PMID- 10205819
TI  - [The physiological role of nitric oxide].
AB  - The review is devoted to exposition of a physiological role of a nitric oxide
      (NO), free radical gas, in various physiological functions. The number of those
      NO involvements is extremely high: bacteriocidal, cytotoxic and antitumor
      leukocyte effects, a relaxation of smooth-muscle cells of both vessels and
      gastrointestinal tract, the name just a few. The scheme of NO formation in
      various biological systems and its targets were shown and neuromodulator
      functions of NO in a brain were analyzed by the review presented. The findings of
      own researches on a role of NO in function of neuro-muscular synapse were
      included by the authors.

PMID- 10205820
TI  - [Can the nervous system functions of mammals be restored during deep cooling
      without warming? New facts and the evolution of views].
AB  - The article provides a review of publications on the most recent theory of cold
      induced paralysis and cold-induced cells dying in mammals. Based on this theory,
      a method of rehabilitation of the nervous system functions was proposed in case
      of cold-induced paralysis with no tissue warming. The facts were provided
      describing rehabilitation of the physiological functions under deep hypothermia.
      Using this own and published data, the author provided the physiological analysis
      of the new data. He concluded that the physiological functions of homoiothermal
      animals and man can be maintained under very low body temperature. The author
      proposed the physiological actions to recover humans from deep accidental (in
      case of accidents) hypothermia. The new theory and the new facts allowed to
      propose new ideas on the origin to homoiothermy and natural hibernation in
      animals.

PMID- 10205821
TI  - [The history of the development of life support systems under the conditions of
      the vacuum of space].

PMID- 10205822
TI  - [The regulation of male sexual behavior by the sex hormones].
AB  - The article provides a review of the clinical and experimental data, both
      published and the author's own observations. They demonstrate that the hormone
      regulation of sex behaviour takes place at the central and the peripheral levels.
      The major role is played by androgenes, of which testosterone is the main
      regulator of sex appeal (libido, courtship behaviour in animals), while the most
      important regulator of ejaculation, in particular, of the time of ejaculation, is
      the non-aromatized androgene dihydrotestosterone (DHT). There is no rigid
      correlation between the level of sex activity and the level of androgenes, if the
      latter are within the normal individual and physiological range. However, both in
      case of hypo- and hyperendrogeny, the observations indicate depression of
      sexuality, though the mechanism of the depression are different. The author
      established the optimal levels of androgenes, which maintain the individual
      elements of the sexual act. The role of estrogene in regulation of the male sex
      appeal is not yet clear. As a rule, use of estrogenes results in depression of
      the male sexuality. At the same time, combination of DHT and estradiole (in
      laboratory and productive animals) leads to normalisation of erection and
      ejaculation disorders. These result is, probably, due to the central effect of
      estrogene, which prolongs the DHT effect and censures its accelerated penetration
      into cellular neuronal structures, as well as to the peripheral effect of DHT.

PMID- 10205823
TI  - [Liposomes and other nanoparticles as drug delivery systems].
AB  - The basic principles of designing of nanoparticle drug delivery systems are
      considered. The special attention is paid to liposomes, because the greatest
      success has been achieved in this area. The modern condition in such intensively
      developing areas as antitumor and, antibacterials drugs, gene therapy, vaccines
      is reviewed.

PMID- 10205824
TI  - [Development of concepts on the biochemistry and pharmacology of melanin
      pigments].
AB  - Biochemical principles of pharmacological action melanin, one of the natural
      cells pigments, are discussed. Melanin is involved into DNA-repair, in the the
      respiratory chain functioning; it modulates such important systems of the
      cellular metabolism as photo- end radio protectors. Melanin neutralizes the
      effect of products of lipid peroxidation and takes part in neurotransmitter
      processes under numerous pathological processes damaging functional neuron
      structures. Experimental data cannot often account for the mechanisms of melanin
      action and therefore systematic analysis of all the data published on melanin
      pigments is necessary for possible employment of melanins for the pharmacological
      needs.

PMID- 10205825
TI  - [Isolation and purification of recombinant truncated (delta2-27) cytochrome P450
      2B4 expressed in E. coli cells as a fusion protein with glutathione-S
      transferase].
AB  - This paper describes the modification of the method by Coon and Pernecky (Meth.
      Enzymol. 1996, 272, 25-34) for purification of truncated (delta 2-27) recombinant
      form of cytochrome P450 2B4 expressed in E. coli as fusion protein with
      glutathione-S-transferase. The modifications included optimisation of conditions
      for proteolytic reaction of fusion protein with thrombine, removal of this
      protease from purified cytochrome P450 preparations using column chromatography
      on hydroxyapatite, introduction of the additional step for obtaining of
      spheroplasts using of lysozyme, and optimisation of conditions for enzyme
      stabilisation during of its purification and storage. The overall yield of
      purified cytochrome was 20% and the specific content of P450 was 14,5 nmol/mg
      protein was measured. This method is suitable for large-scale isolation of high
      purified cytochromes P450 which are necessary for study of structure-functional
      relationships of this hemoprotein with protein partners as well as for
      investigation of its structure and mechanism of action.

PMID- 10205826
TI  - [Interstrain differences in enzymatic activity of CYP2B1 and expression of its
      gene in the rat liver during induction with phenobarbital and triphenyldioxane].
AB  - The interstrain differences in hepatic 7-pentoxyresorufin-O-dealkylase and 16
      beta-androstendione hydroxylase activities specific for cytochrome P450 2B1 have
      been found in Sprague-Dawley, Brattleboro and Wistar rats treated with with
      phenobarbital, triphenyldioxane. Similar differences were found in the
      accumulation of corresponding mRNAs suggesting differences in expression of
      cytochrome P450 gene. Analysis of the enzymatic activity and mRNA level revealed
      positive correlation between these parameters. Thus, differences in
      transcriptional activity of CYP2B1 gene during induction by phenobarbital and
      triphenyldioxane may be one of reasons for interstrain differences between
      enzymatic activities of rat liver cytochrome P4502B1.

PMID- 10205827
TI  - [Binding of transcription factors with functionally significant regions of MDR1
      gene promoter during its activation].
AB  - Interaction of transcription factors with functional regions of gene mdr1
      promoter has been studied. Binding of transcription factors to double-stranded
      (ds) oligonucleotides, mimicking four important regulatory regions before and
      after treatment of KB and K-562 cell lines with doxorubicin, cytarabine, and
      vinblastine was analysed by gel-shift assay. Gene induction resulted in
      enhancement of the main complex A(A1) proteins formation on the all four regions
      in both the cell lines. Inhibition of each complex formation by an excess of non
      radiolabelled ds oligonucleotides suggests the possibility of regions interaction
      during promoter activation. Another indication of interaction of regulatory
      regions during activation is overlapping minor complexes sets. The results
      suggest that the four studied regulatory regions are important for mdr1 gene
      activation. Corresponding oligonucleotides mimicking these regions can be
      employed as inhibitors of gene transcription that bind specific transcriptional
      factors.

PMID- 10205828
TI  - [Reserve of serum lipids for peroxidation during oxidative stress in rats].
AB  - The index quantitatively characterizing the serum lipids reserve for peroxidation
      (SLRP) was developed and evaluated in rats with simulated toxic (CCl4) hepatitis.
      The index represents a ratio of malondialdehyde (MDA) concentrations in serum
      before and after stimulation of peroxidation by Fe2+ ions (in the same sample).
      The index SLRP allows to evaluate direction and the intensity of imbalance among
      prooxidants action and the total activity of serum lipids antioxidant system even
      when there is no change of MDA basal level.

PMID- 10205829
TI  - [Changes in lymphocyte and erythrocyte membrane microviscosity in cancer
      patients].
AB  - Lymphocyte and erythrocyte membrane microviscosites of lipid-protein contact
      zones and lipid bilayer in blood of patients with gastric, urinary bladder and
      ovary cancers were investigated in comparison with healthy volunteers by means of
      coefficients of eximerization of fluorescent probe pyrene. The decrease of
      membrane fluidity (i.e. the increase of microviscosity) was revealed in blood
      cell membranes of patients with diffuse cancers of studied localizations. In the
      case of ovary cancer membrane fluidity decreased significantly only in patients
      with ascite form of the disease. The most pronounced increase of microviscosity
      was observed in lymphocytes and especially in erythrocytes of practically
      incurable patients. Interrelationship between microviscosity and other processes
      that influence on structural properties of membranes under malignancy and their
      functional role are discussed.

PMID- 10205830
TI  - [Amino acids and their metabolites in blood and urine of children with minimal
      cerebral dysfunction].
AB  - The following changes were found in children in the minimal cerebral dysfunction:
      the hypoaminoacidemia and hypoaminoaciduria with decrease of glutamate and
      aspartate, their amides, methionine and serine in the blood and urine; decrease
      of lysine, taurine, tyrosine, catecholamines and serotonin in the blood; increase
      of GABA and glycine in the blood; increase of xanthurenate, proline and cysteine
      in the urine. The ratio excitatory/inhibitory mediatory amino acids decreased
      significantly. The ratio essential/nonessential amino acids and concentrations of
      amino acids, transporting by x-AG, beta and A/ASC systems, decrease in the blood;
      majority of transporting systems in the kidney functions augmently. Disturbances
      of amino acids metabolism disappear or decrease in successful treatment.

PMID- 10205831
TI  - Enzyme-linked immunosorbent assay for apolipoproteins A-I and B in the urine of
      patients with nephrotic syndrome.
AB  - Enzyme-linked immunosorbent assay (ELISA) has been used for measuring
      apolipoproteins A-I and B in the urine. ApoB is absent in urine of healthy
      subjects, and apoA-I is determined in trace quantity. In patients with chronic
      glomerulonephritis quantity of apoA-I in urine was 117 times as much as in
      control group. ApoB is present in urine of patients in considerable quantity
      (1528 +/- 315 micrograms/l). The ELISA method for determining apoA-I and apoB in
      urine makes it possible to evaluate the gravity of pathological process in
      kidney.

PMID- 10205832
TI  - [A simple method of measuring superoxide dismutase activity using
      photochemiluminescence].
AB  - At present, photochemical detection of SOD-activity is used in most cases, where
      superoxide production is based on the NADPH oxidase activity or autooxidation of
      some substances, for instance, adrenaline. The shortcomings of these assays are
      the requirement of stable pH and temperature and need long-term experiments and
      sophisticated preliminary work. For this reason a novel method to determine SOD
      activity have been proposed, based on the photochemiluminescence (PCL), where
      riboflavine is used as a photosensitizer and lucigenin as a free-radical
      detector. Minimal concentrations of the system components have been selected, at
      which PCL intensity became virtually independent on the concentration and was
      sufficient for proper measurements: 25 nmole/ml of riboflavine, 3 nmole/ml of
      lucigenin and 250 nmole/ml of methionine. Under this conditions, the amount of
      SOD causing two-fold inhibition of PCL was 10 +/- 0.3 ng of SOD (Sigma, USA).
      Antioxidants occurring in the blood changed the PCL intensity by 5% at following
      concentrations: ascorbic acid--above 3.6 microM, uric acid--above 0.3 microM,
      glutathione--above 4.0 microM. Taking into account the amount of these
      antioxidants in whole blood and erythrocytes, it has been calculated that the
      antioxidants containing in the sample do not influence the results of SOD assay,
      even without erythrocytes washing. The proposed method was compared with a
      procedure offered by Calbiochem. The amounts of SOD causing two-fold decrease of
      PCL in our method and that of Calbiochem, were 10 and 40 ng (Sigma, USA), and
      standard deviations 0.45 and 0.96%, respectively. The SOD activity from 107
      healthy donors (76 males and 31 females, 40 smokers and 67 non-smokers) has been
      determined and was found to be 15.1 +/- 0.4 ng SOD/1 x 10(9) erythrocytes.

PMID- 10205834
TI  - [Disorders of speech and imagery functioning in children with epilepsy in the
      right or left cerebral hemisphere as primary loci of lesions].
AB  - The paper presents the relationship between the disorders of speech and a
      drawing. 40 epileptic 5-12 year-old children as well as 9 healthy children (a
      control group) were examined. There were analysed the disorders of speech,
      alterations of drawing in children with epilepsy, mechanisms of participation of
      the right or the left hemisphere in forming of speech and descriptive activity on
      different stages of ontogenesis and its compensation in dependence on the
      severity of the disease. In younger preschool age disorders of a speech and
      deficiency in drawing were determined by the damages of the right hemisphere,
      while a role of the left hemisphere in such processes increased later.

PMID- 10205833
TI  - [On the etiology of epileptic seizures in children of the first year of life].
AB  - The paper presents the analysis of unfavourable ante- and intranatal factors as
      well as the data of neurosonography of 109 children with the fits during the
      first year of life and of 58 children with hypoxic-ischemic encephalopathy
      without convulsions. The high degree of the correlation was found between
      complications of the first half of pregnancy and the disturbances of growth and
      development of a child. Frequency of a trauma in the course of a delivery
      correlated with frequency of asphyxia. A persistence of a germinative matrix and
      signs of functional immaturity of the brain suggested the important role of both
      focal and multifocal cerebral dysplasias in the genesis of epileptic fits at the
      early stages of ontogenesis. In children with nonmalignant neonatal and
      idiopathic fits there were some nonvisualized cortical disorders that became
      pronounced under hypoxic-dysmetabolic conditions in the first case and during a
      period of the following maturation of axon-dendritic bounds and of the increase
      of neuronal activity in the second case.

PMID- 10205835
TI  - [Algesic manifestations of depression in children and adolescents].
AB  - Under conditions of a general somatic hospital were examined 148 children and
      adolescents at the age of 3-16 years with different algesic manifestations
      (cephalgias, myalgias, cardialgias). In all the patients there were depressive
      disorders of neurotic level of different degree of severity. In dependence on the
      primary affective disorder, ive propose a typology of the depressions that
      distinguish asthenic, anxious, melancholic and combined (asthenic-anxious,
      anxious-melancholic) variations. Differential therapy of 89 patients was
      performed taking into a consideration both the role of depression in pathogenesis
      of algesias and typologic variations of depressive disorders. Symptomatic
      treatment was administered to 59 patients. In group with pathogenetic
      (antidepressive) therapy either recovery or considerable improvement was achieved
      in 70.8% of the cases; meanwhile considerable improvement was found only in 6.8%
      of the patients from a group with symptomatic treatment.

PMID- 10205836
TI  - [Diagnosis and treatment of Rolandic epilepsy].
AB  - Rolandic epilepsy belongs to the most frequent forms of epilepsy in children. 43
      patients aged 2-14 years were observed. Complex neurologic, genealogic,
      neurophysiologic and neuroradiologic examinations was performed. There was a
      microfocal symptomatology in the form of ptosis and syndrome of infantile
      cerebral paralysis. The changes found at neuroradiologic examination were not
      related to the location of an epileptic focus and didn't influence the prognosis
      of the disease. In 10 cases electroencephalographic patterns were observed in
      clinically healthy relatives. In all the patients a remission of the fits was
      achieved. Administration of low doses (20 mg/kg daily) of valproic acid (depakin)
      resulted in a remission of the fits.

PMID- 10205838
TI  - [The status of adaptive-compensatory mechanisms after the brain concussion in
      children].
AB  - 80 children of preschool age were observed after concussion of the brain. In
      follow-up from 6 months 3 years clinical-anamnestic and neuropsychologic methods
      were used. The functions of autonomic nervous system were evaluated according to
      the results of estimation of initial autonomic tonus, autonomic reactivity,
      autonomic maintenance of the activity and the data of cardiointervalography. The
      state of nonspecific systems of the brain was studied with day time polygraphic
      research with a visual EEG evaluation, construction of histogramms by Fora
      method, estimation of speed and order of the fading of the components of a rough
      response. Psychovegetative stress was the ground for neurologic disorders in
      posttraumatic period. The disorders of adaptive regulation were manifested in
      exhausting of ergotropic systems with compensatory overstrain of trophotropic
      mechanisms, resulted in predominance of inhibiting influences with an inadequate
      response of synchronization on EEG during functional loads. Severity of clinical
      manifestations and disorders of adaptive regulation were more pronounced in
      children 1-3 year-old and with hypoxic-traumatic damages of the brain in
      anamnesis. Disintegration of cerebral activity correlated with the remote period.
      In the first 6-12 months after the concussion of the brain changes of vegetative
      reactivity prevailed, after 18 months the alterations in vegetative maintenance
      progressed.

PMID- 10205837
TI  - [The use of sirdalud in the treatment of spasticity in infantile cerebral palsy].

PMID- 10205839
TI  - [The detection of cerebral circulation changes in children by Doppler
      ultrasonography in ambulatory care].
AB  - To determine the role of ultrasonic and transcranial dopplerography in
      investigation of both arterial and venous systems of children's head in
      conditions of outpatient clinic were observed 100 children aged 4-14 years with
      autonomic dysfunction, migraine, neurosis-like and closed cerebrocranial trauma
      (concussion of the brain). There were estimated the qualitative indices of
      dopplerography (a form, distributions of the frequencies in spectrum, direction
      of the blood flow, acoustic characteristics) and quantitative indices (systolic,
      diastolic, mean rate of blood flow, indices RI and S/D) and alterations in venous
      circulation. In all the groups of children there were found angiodystonic
      manifestations in the form of the increase of vessels resistance in 87.5-97.6% of
      the patients; besides, the signs of venous dysgemia were observed in 28-50% of
      the cases.

PMID- 10205840
TI  - [Computerized electroencephalography of acute neuro-infections in children].
AB  - Spectral and visual analysis of EEG was performed in 156 children with acute
      neuroinfections. It revealed some variants of EEG tracings, related to different
      grades of a compensation of intracranial hypertension (ICH), the changes in
      cerebral blood flow and a level of a damage of brainstem in dislocation syndrome.
      In patients with compensated and subcompensated ICH a polyrhythmic EEG was
      registered, while the changes in cerebral blood flow were moderate. 91% of the
      patients of these groups completely recovered. The patients with decompensated
      ICH and with mesencephalic level of brain dislocation had slow monotonous EEG;
      those with bulbar lesion had a suppression of bioelectric activity; a decrease of
      cerebral blood flow as well as an impaired autoregulation were observed. 5
      patients from this group died, and the others survived with neurologic
      impairments of different degree. The conclusion was made about the dependence of
      EEG character in acute period of neuroinfection on the grade of the elevation of
      intracranial pressure and on the level of the brainstem damage and about the
      possibility to prognose an outcome of the disease on the basis of EEG
      characteristics.

PMID- 10205841
TI  - [Electroencephalographic correlates of schizophrenic type mental disorders at an
      early age in childhood].
AB  - Electroencephalographic study was performed in 30 children of 1-3 years old from
      the group with the high risk of schizophrenia. Clinical observation of the
      patients was performed in the period of EEG recording and follow-up study was
      also made during 10-12 years. Three groups of patients were picked out with the
      differences in both clinical and electrophysiologic indices. Bundle beta-activity
      was registered on EEG in the cases of an active schizophrenic process. A presence
      of the spindles of the sleep and their dominance on EEG were characteristic for
      children with nonprocessual disorders of psychopathic-like type with
      disinhibition of the drives. Hypersynchronism of delta- and theta-activities were
      observed in the cases of schizotypic diathesis and an early children's autism
      with the predominance of paroxysmal somato-autonomic disorders.

PMID- 10205842
TI  - [The dystrophin gene structure in patients with Duchenne myodystrophy].
AB  - The study was performed of the alterations within 17 exons and promoter region of
      dystrophin gene by means of multiplex DNA amplification in boys of Slavonic
      population with clinical diagnosis of muscular Duchenne's dystrophy. The
      dystrophin gene's deletions were found in different exons of 11 boys from 33
      examined families, that is in 33% of the families. In 8 cases the deletions were
      clustered near a central part of dystrophin gene.

PMID- 10205843
TI  - [Nerve growth factor auto-antibodies in the sera of mothers of schizophrenic
      children and children from high risk group].
AB  - A level of autoantibodies (aAB) to nerve growth factor (NGF) was measured in
      blood serum of children from 4 groups: 1) schizophrenic patients; 2) children
      from the families, in which one of the parents suffered with schizophrenia (high
      risk groups of schizophrenia); 3) children with residual-organic damages of CNS;
      4) control group. This index was also determined in their mothers. Significant
      elevation of a titer of aAB to NGF was observed in blood of children from groups
      1 and 2 as well as in their mothers, as compared with 3 and 4 groups. Among the
      mothers of the children from 1 and 2 groups there were met women with different
      endogenous mental disorders, with the disorders of personality as well as
      mentally healthy women. An increase of a level of aAB to NGF was found in all the
      women from groups 1 and 2, independently of their mental status including
      mentally healthy women. Such results allow to consider elevated level of aAB to
      NGF as a risk factor of mental pathology.

PMID- 10205844
TI  - [Prevalence of anorexia nervosa in urban population of adolescents].

PMID- 10205846
TI  - [Focal cortical dysplasia].

PMID- 10205845
TI  - [Brain surgery in Russia (on the 150th anniversary of the birth of A.S.
      Taubera)].

PMID- 10205847
TI  - [Corpus callosum dysgenesis and interhemispheric dysfunctions].

PMID- 10205848
TI  - [Contemporary views on Rett's syndrome: clinical, cytogenetic and molecular
      studies].

PMID- 10205849
TI  - Stereoselective synthesis of new beta-lactams by cyclocondensation of 1-methoxy-3
      (trimethylsilyloxy)-1,3-butadiene with 4-formyl substituted azetidinones.
AB  - The BF3.OEt2 or LiClO4 catalyzed hetero Diels-Alder reaction of 1-methoxy-3
      (trimethylsilyloxy)-1,3-butadiene (Danishefsky's diene) with enantiomerically
      pure 4-formylazetidin-2-ones affords the corresponding cycloadducts in fair to
      good yields and in diastereoisomeric ratios of up to 98:2.

PMID- 10205851
TI  - Photobiological studies of new cyclopentene-psoralens.
AB  - Psoralen analogues bearing a cyclopentane ring fused to either the 4',5' double
      bond (compound 4) or the 3,4 double bond (compound 7) of the tricyclic
      furocoumarin structure were prepared. AM1 theoretical calculations performed for
      these compounds indicated that the electronic properties of their reactive double
      bonds were very similar to those of psoralen and its derivative 8-methoxypsoralen
      (8-MOP), though the overall molecular geometries were clearly different,
      particularly as regards the change in molecular curvature produced by the
      introduction of the cyclopentane ring. Compound 4 showed a capacity similar to
      that of 8-MOP to inhibit the growth of human cervix adenocarcinoma cells (HeLa)
      and to induce mutagenic effects, but it was definitely less phototoxic to skin
      than 8-MOP. Its ability to photoadd to DNA and to cross-link DNA strands was also
      demonstrated. Instead, compound 7 was practically devoid of biological activity
      and no interaction with the macromolecule could be detected. These differences in
      behaviour between 4 and 7 are probably due to the molecular curvature resulting
      from the introduction of the cyclopentane ring.

PMID- 10205852
TI  - Chromatographic indexes on immobilized artificial membranes for the prediction of
      transdermal transport of drugs.
AB  - A set of 12 drugs, consisting of structurally unrelated neutral, basic, acidic
      and amphoteric compounds, was examined by high performance liquid chromatrography
      (HPLC) on a model of fluid membrane bilayers, the immobilized artificial membrane
      (IAM) column. The logarithms of chromatographic capacity factors extrapolated to
      100% aqueous phase at pH 5.5 (log kw) were measured and compared to the n
      octanol/water partition coefficients (log P). The scale derived from the IAM
      system was different from the lipophilicity scale expressed by the log P, due to
      the peculiar capability of phospholipids to well accommodate the ionized form of
      some molecules and show additive or repulsive extra-interactions when particular
      structural motifs on the molecule are present. The relationship between log P and
      log kw previously obtained for compounds interacting on IAM phase by a uniquely
      lipophilicity-based mechanism, allowed us to calculate, from log P, the values of
      log kw expected for the drugs considered. These values were subtracted from the
      log kw experimentally determined and the differences were assumed to quantify the
      amount of extra-interactions (hydrogen bond and electrostatic interactions) with
      phospholipids (delta log kw). The coefficients of permeability through the human
      skin (Kp) for the compounds considered did not correlate with either log kw or
      log P values. However, the Kp values correlated well with the delta log kw values
      indicating that the higher the ability of a molecule to cross the skin barrier,
      the lower its component of interaction with phospholipids not accounted for by
      lipophilicity-based interactions.

PMID- 10205850
TI  - Antisense activity of an anti-HIV oligonucleotide conjugated to linear and
      branched high molecular weight polyethylene glycols.
AB  - An anti-HIV 12mer oligonucleotide (ODN) conjugated to two different high
      molecular weight monomethoxy polyethylene glycols (MPEGs) has been tested for its
      antisense activity. The capacity of these conjugates to protect the MT-4 cells
      against HIV infection has been compared to the unmodified, native ODN, and the
      effect of the different structures of the supporting polymer has been discussed.
      It was found that only the ODN conjugated to the linear MPEG shows an anti-HIV
      activity in the investigated conditions. The same 12mer, when conjugated to a
      branched (MPEG)2, is fully inactive, as well as the native, unmodified ODN.

PMID- 10205854
TI  - Synthesis and D2-like binding affinity of 4,5-dihydro-1H-benzo[g]indole-3
      carboxamide derivatives as conformationally restricted 5-phenyl-pyrrole-3
      carboxamide analogs.
AB  - A series of 4,5-dihydro-1H-benzo[g]-indole-3-carboxamide derivatives 2a-g were
      synthesized as conformationally restricted analogs of the dopamine D2-like 5
      phenylpyrrole-3-carboxamide ligands and evaluated for their affinity for the
      dopamine D2-like receptors. In this series, N3-[(1-ethyltetrahydro-1H-2
      pyrrolyl)methyl]-4,5-dihydro-1H-benzo[ g]indole- 3-carboxamide (2a) showed the
      highest affinity for D2-like receptors (IC50 = 160 nM). Replacement of the N-(1
      ethyl-2-pyrrolidinyl)methyl side chain with a 2-(N,N-diethylamino)ethyl or a 1
      benzyl-4-piperidinyl group (2b, 2d) decreased affinity for the D2-like receptor.
      The other compounds tested were found to be devoid of D2-like binding affinity.

PMID- 10205853
TI  - Benzocondensed derivatives as rigid analogues of the mu-opioid agonist 3(8)
      cinnamyl-8(3)-propionyl-3,8-diazabicyclo[3.2.1]octanes: synthesis, modeling, and
      affinity.
AB  - A new series of rigid analogues (1a-g, 2a-g) of the previously reported analgesic
      3-cinnamyl-8-propionyl-3,8-diazabicyclo[3.2.1]octane (I) and its reverted isomer
      3-propionyl-8-cinnamyl (II) were synthesized, in which the cinnamyl substituent
      is incorporated in benzocondensed bicyclic systems. Binding assays for the
      affinity towards mu receptors indicated that, while in the reverted series 2 the
      beta-naphthylmethyl (2d) and the benzocycloheptenylmethyl derivative (2g)
      favorably compared with II, all compounds 1 displayed a mu-affinity lower than
      that of the parent I. Modeling studies suggest that the flexibility of the
      cinnamyl side chain plays an important role for activity.

PMID- 10205855
TI  - Determination of bezafibrate concentration by high performance liquid
      chromatography in serum of rats treated with lead nitrate.
AB  - In the present study, the bezafibrate levels were measured in serum of rats
      treated with lead nitrate using a high performance liquid chromatography (HPLC)
      method. The results have shown that the peak corresponding to bezafibrate in the
      chromatogram is reduced in serum of rats treated with bezafibrate plus lead,
      indicating that lead treatment accelerates the metabolism of bezafibrate in rats.

PMID- 10205856
TI  - Synthesis via carbon suboxide and pharmacological activity of coumarin
      derivatives.
AB  - This report sums up the research work since 1993 on the synthesis of coumarin
      derivatives using carbon suboxide as reagent.

PMID- 10205857
TI  - New cycloalkylpyrazoles as potential cyclooxygenase inhibitors.
AB  - In this study some cycloalkyl-3-(N-substituted carbamoyl)-1-phenylpyrazoles have
      been synthesized in order to screen their capability to inhibit human
      cyclooxygenase. The synthetic pathway is based on the well known property of
      nitrilimines to undergo 1,3-dipolar cycloaddition reactions. The structures of
      all the synthesized compounds have been elucidated by means of both analytical
      and spectroscopic methods.

PMID- 10205858
TI  - Synthesis and activity of cephalosporins containing an oxyiminomethylene
      functionality in the ortho-position of a phenyl- or phenoxyacetic acid C-7 side
      chain substituent.
AB  - A new series of cephalosporins having in the C-7 side chain a phenyl- or a
      phenoxyacetamido group bearing an oxyiminomethyl function in the ortho-position
      of the aromatic ring was prepared. Their in vitro activity was tested against
      both Gram+ and Gram- strains.

PMID- 10205859
TI  - Attentional effects on preattentive vision: spatial precues affect the detection
      of simple features.
AB  - Most accounts of visual perception hold that the detection of primitive features
      occurs preattentively, in parallel across the visual field. Evidence that
      preattentive vision operates without attentional limitations comes from visual
      search tasks in which the detection of the presence of absence of a primitive
      feature is independent of the number of stimuli in a display. If the detection of
      primitive features occurs preattentively, in parallel and without capacity
      limitations, then it should not matter where attention is located in the visual
      field. The present study shows that even though the detection of a red element in
      an array of gray elements occurred in parallel without capacity limitations, the
      allocation of attention did have a large effect on search performance. If
      attention was directed to a particular region of the display and the target
      feature was presented elsewhere, response latencies increased. Results indicate
      that the classic view of preattentive vision requires revision.

PMID- 10205860
TI  - Elements or objects? Testing the movement filter hypothesis.
AB  - P. McLeod, J. Driver, and J. Crisp (1988) proposed the existence of a movement
      filter in the human early visual system. This filter preattentively segregates
      all moving stimuli in the visual field from all stationery stimuli (McLeod et
      al., 1988) and all stimuli moving in one direction from those moving in another
      (P. McLeod, J. Driver, Z. Dienes, & J. Crisp, 1991). The primary experimental
      paradigm that provides evidence for the movement filter is the visual search
      task. McLeod et al. (1988) demonstrated that a target defined by motion and shape
      perceptually pops out of a conjunctive display. Four experiments are presented
      that demonstrate that the output of the movement filter may depend on global
      characteristics of the display. When a moving element perceptually groups with a
      static object, preattentive segregation does not occur. However, when the same
      element does not perceptually group with a static object, preattentive
      segregation occurs.

PMID- 10205861
TI  - Perceiving surface slant from deformation of optic flow.
AB  - Perceived surface orientation and angular velocity were investigated for
      orthographic projections of 3-D rotating random-dot planes. It was found that (a)
      tilt was accurately perceived and (b) slant and angular velocity were
      systematically misperceived. It was hypothesized that these misperceptions are
      the product of a heuristic analysis based on the deformation, one of the
      differential invariants of the first-order optic flow. According to this
      heuristic, surface attitude and angular velocity are recovered by determining the
      magnitudes of these parameters that most likely produce the deformation of the
      velocity field, under the assumption that all slant and angular velocity
      magnitudes have the same a priori probability. The results of the present
      investigation support this hypothesis. Residual orientation anisotropies not
      accounted for by the proposed heuristic were also found.

PMID- 10205862
TI  - The utility of motion parallax information for the perception and control of
      heading.
AB  - Two experiments in which participants were given control over the direction of
      computer-simulated self-motion were conducted. Environments were designed to
      evaluate the functionality of simple and multiple motion parallax as well as a
      separation ratio (sigma; indexing the separation of 2 objects in depth) for the
      perception and control of heading. Results provide a 1st indication of optimizing
      performance in the top end of the global optical flow velocity range available
      during human bipedal self-motion. The introduction of sigma, developed to explain
      performance improvements with decreasing distance to the target, was able to
      account for most of the performance differences among all simulated environments.
      The rate of change in horizontal optical separation between at least 2
      discontinuities was identified as a likely candidate for the optical foundation
      of the perception and control of heading during target approach.

PMID- 10205863
TI  - Perceptual depth synthesis in the visual system as revealed by selective
      adaptation.
AB  - Selective adaptations was used to determine the degree of interactions between
      channels processing relative depth from stereopsis, motion parallax, and texture.
      Monocular adaptations with motion parallax or binocular stationary adaptation
      caused test surfaces, viewed either stationary binocularly or monocularly with
      motion parallax, to appear to slant in the opposite direction compared with the
      slant initially adapted to. Monocular adaptations on frontoparallel surfaces
      covered with a pattern of texture gradients caused a subsequently viewed test
      surface, viewed either monocularly with motion parallax or stationary
      binocularly, to appear to slant in the opposite direction as the slant indicated
      by the texture in the adaptation condition. No aftereffect emerged in the
      monocular stationary test condition. A mechanism of independent channels for
      relative depth perception is dismissed in favor of a view of an asymmetrical
      interactive processing of different information sources. The results suggest
      asymmetrical inhibitory interactions among habituating slant detector units
      receiving inputs from static disparity, dynamic disparity, and texture gradients.

PMID- 10205864
TI  - Using eye height in different postures to scale the heights of objects.
AB  - Four experiments examined eye height (EH) scaling of object height across
      different postures. In Experiment 1, participants viewed rectangular targets
      while they were standing, seated, and prone. Standing and seated judgments were
      similar, possibly due to EH scaling. Prone judgments were significantly lower, a
      result not attributable to the unfamiliarity of that posture (Experiment 2). In
      Experiment 3, shifts of seated EH produced height overestimations equivalent to
      those of standing viewers. Experiment 4 examined the visual salience of size
      information in the seated and prone judgments by holding EH constant and
      manipulating another source: linear perspective. Participants viewed targets
      placed on true- and false-perspective (FP) gradients. The FP gradient affected
      prone judgments but not seated judgments, which presumably relied on EH. It
      appears that the human visual system weights size information differentially
      depending on its utility.

PMID- 10205865
TI  - Shedding some light on catching in the dark: perceptual mechanisms for catching
      fly balls.
AB  - To catch a lofted ball, a catcher must pick up information that guides locomotion
      to where the ball will land. The acceleration of tangent of the elevation angle
      of the ball (AT) has received empirical support as a possible source of this
      information. Little, however, has been said about how the information is
      detected. Do catchers fixate on a stationary point, or do they track the ball
      with their gaze? Experiment 1 revealed that catchers use eye and head movements
      to track the ball. This means that if AT is picked up retinally, it must be done
      by means of background motion. Alternatively, AT could be picked up by
      extraretinal mechanisms, such as the vestibular and proprioceptive systems. In
      Experiment 2, catchers reliably ran to intercept luminous fly balls in the dark,
      that is, in absence of a visual background, under both binocular and monocular
      viewing conditions. This indicates that the optical information is not detected
      by a retinal mechanism alone.

PMID- 10205866
TI  - Better discrimination of small changes in commonly encountered than in less
      commonly encountered auditory stimuli.
AB  - Results from 3 auditory tasks revealed that small changes made in stimuli
      commonly encountered in everyday life are more easily discriminated than are the
      same changes made in stimuli not as commonly encountered. The tasks required
      discrimination of a frequency difference in 1 tone of 6-tone chords or nonchords,
      discrimination of a duration difference in 1 note of common tunes or nontunes,
      and discrimination of the deletion of a band of frequencies from speech sounds
      played forward or backward. Different crews of college-aged listeners served in
      the different tasks. If future research shows this difference in discriminability
      to be a general property of commonly encountered stimuli--attributable to a
      difference in the way they are processed in the nervous system--then
      discrimination tests of this sort could become useful for assessing whether
      stimuli have made the transition from one form of processing to the other.

PMID- 10205867
TI  - Reading homographs: orthographic, phonologic, and semantic dynamics.
AB  - Reading processes were compared across 3 word types: homographs (separate
      pronunciations and meanings, such as lead), homonyms (singular pronunciations but
      separate meanings, such as spring), and control words (e.g., clock). In
      Experiment 1, naming reaction times were significantly slower to homographs than
      to all other words. Experiments 2 and 3 used an association judgment task, with
      referent words related to the dominant or subordinate meanings of homonyms and
      homographs. In Experiment 2, homonyms and homographs were presented 1st, followed
      by disambiguating associates. In Experiment 3, presentation order was reversed.
      For homographs, performance costs always occurred for subordinate meanings. For
      homonyms, these costs vanished when context was provided by the preceding
      associates. The data underscore the priority of phonologic information in word
      meaning access and suggest that low- and high-level constraints combine to shape
      word perception.

PMID- 10205868
TI  - The convergent validity of MMPI and Rorschach scales: an extension using profile
      scores to define response and character styles on both methods and a
      reexamination of simple Rorschach response frequency.
AB  - Past research indicated the convergence of Rorschach and MMPI scales may be a
      function of (a) simple Rorschach response frequency (R) or (b) complex response
      character styles on both methods. In this study, new criteria were developed for
      defining the second assumption using F and K from the MMPI and R and Lambda from
      the Rorschach. Although substantially different from the factor criteria used
      previously (KS = .45 and .30), the new criteria still produced the expected
      pattern of correlations among MMPI and Rorschach scales. Averaged across 17
      constructs, the new criteria produced strong validity coefficients for patients
      with similar styles (M composite r = .50), though they were less effective for
      patients with discordant styles (M composite r = -.27). It was also demonstrated
      that R by itself does not moderate convergent validity. Rather, statistical
      modeling with two sets of 300 random samples (a) demonstrated the prior findings
      related to R were the result of sampling error and (b) supported the general
      hypothesis that Rorschach and MMPI scales correlate to the extent response
      character styles correlate. Implications are considered.

PMID- 10205869
TI  - Comparative validity of the MMPI-2 Wiener-Harmon subtle-obvious scales in male
      prison inmates.
AB  - The Wiener-Harmon subtle-obvious MMPI subscales (Wiener, 1948; Wiener & Harmon,
      1946) have been the subject of considerable debate. In this study, we examined
      the intercorrelations among full clinical scale T scores and their subtle and
      obvious subscales in an offender population. Low subtle to full-scale
      correlations were observed, suggesting that these items contribute little to full
      scale scores. Further, we explored the criterion validity of the MMPI-2 subtle
      obvious scales in this forensic sample. The results demonstrated that the obvious
      scales of the MMPI-2 had greater criterion validity than the subtle scales when
      compared to crime history data. Scores on the subtle subscales were unrelated to
      crime history. The Ma-O subscale demonstrated the strongest association to crime
      history data. The findings from this study add to a mounting body of evidence
      indicating that when respondents are in a position to understand item content,
      and can therefore provide a direct self-appraisal, responses are most predictive
      of clinical criteria.

PMID- 10205871
TI  - Testing the equivalence of the socialization factor structure for criminals and
      noncriminals.
AB  - Considerable evidence supports the criterion-related validity of the
      Socialization (So) scale of the California Psychological Inventory (Gough, 1948,
      1994, 1996) for the prediction of antisocial and prosocial behavior. However, no
      research has examined the similarity of the So construct for the two populations.
      Meaningful interpretation of So scores is possible if the factor structure is
      equivalent for antisocial and prosocial groups.

PMID- 10205870
TI  - Family patterns of perfectionism: an examination of college students and their
      parents.
AB  - We examined patterns of perfectionism among college students and their biological
      parents in a sample of 188 undergraduates from intact families. Ratings (self vs.
      other) showed the greatest degree of convergence when daughters were either the
      target or the rater. Levels of self-oriented perfectionism in students were
      positively associated with the levels characterizing the same-sex parent, but
      unrelated (father-daughter) or negatively related (mother-son) to the levels
      characterizing the opposite-sex parent. Finally, parents' other-oriented
      perfectionism was not significantly related to students' socially prescribed
      perfectionism.

PMID- 10205872
TI  - Rorschach aggression variables: a study of reliability and validity.
AB  - This study investigated the extent to which 6 Rorschach variables of aggression
      (A1, A2, AG, MOR, AgC, AgPast) are related to one another, to the Diagnostic and
      Statistical Manual of Mental Disorders (4th ed. [DSM-IV]; American Psychiatric
      Association, 1994) Cluster B personality disorder criteria, and to self-report
      measures of anger, aggression, and antisocial behavior. Seventy-eight patients
      were found to meet DSM-IV criteria for an Axis II disorder, Cluster A personality
      disorder (paranoid, schizoid, schizotypal) = 9, Cluster B (antisocial personality
      disorder [ANPD] = 16, borderline personality disorder [BPD] = 23, histrionic
      personality disorder = 5, narcissistic personality disorder = 12) = 56, and
      Cluster C personality disorder (avoidant, dependent, obsessive-compulsive) = 13.
      The results of this study indicated that (a) these 6 Rorschach aggression
      variables can be scored reliably; (b) 2 factors, revealed by factor analysis,
      accounted for 77% of the total variance; (c) selected variables were found to be
      empirically related to DSM-IV diagnostic criteria for ANPD and BPD; and (d)
      selected variables were found to be empirically related to a self-report measure
      of anger and antisocial practices. The conceptual nature and clinical utility of
      these Rorschach aggression variables as well as implications for future research
      are discussed.

PMID- 10205873
TI  - Factor-based prototypes of the Millon Adolescent Clinical Inventory in
      adolescents referred for residential treatment.
AB  - Although well received by the clinical community, there have been few published
      reports on the use of the Millon Adolescent Clinical Inventory (MACI). There have
      been no published studies describing use of the MACI with a residential treatment
      population. In addition, there have been no published reports investigating the
      factor structure of the MACI. A principal components factor analysis was
      performed for all MACI scales and sex for 251 adolescents referred to a
      residential treatment facility. Five factors were found accounting for 77.4% of
      the variance. Factor-based prototypes were generated from these results: Factor 1
      defines a prototype for Defiant Externalizers, Factor 2 for Intrapunitive
      Ambivalent Types, Factor 3 for Inadequate Avoidants, Factor 4 for Self
      Deprecating Depressives, and Factor 5 for Reactive Abused Types. Prototype
      descriptions and clinical vignettes are included for each of the 5 factor-based
      prototypes. These results are consistent with our clinical experience with this
      population. Prototype analysis may offer a powerful way of enhancing the utility
      of the MACI in clinical settings.

PMID- 10205874
TI  - Rhodopsin and phototransduction.
AB  - Recent studies on rhodopsin structure and function are reviewed and the
      properties of vertebrate as well as invertebrate rhodopsin described. Open issues
      such as the 'red shift' of the absorbance spectra are emphasized in the light of
      the present model of the retinal-binding pocket. The processes that restore the
      rhodopsin content in photoreceptors are also presented with a comparison between
      vertebrate and invertebrate visual systems. The central role of rhodopsin in the
      phototransduction cascade becomes evident by examining the main reports on light
      activated conformational changes of rhodopsin and its interaction with
      transducin. Shut-off mechanisms are considered by reporting the studies on the
      sites of rhodopsin phosphorylation and arrestin binding. Furthermore, recent
      findings on the energetics of phototransduction point out that the ATP needed for
      photoreception in vertebrates is synthesized in the outer segments where
      phototransduction events take place.

PMID- 10205875
TI  - Photosensitization of human skin cell lines by ATMPn (9-acetoxy-2,7,12,17
      tetrakis-(beta-methoxyethyl)-porphycene) in vitro: mechanism of action.
AB  - 9-Acetoxy-2,7,12,17-tetrakis-(beta-methoxyethyl)-porphycene (ATMPn) is a
      promising new photosensitizer characterized by high absorption around 640 nm and
      high singlet oxygen yield. To study the mechanism of action in vitro we have
      investigated uptake, intracellular localization, cell survival and
      ultrastructural changes following photodynamic treatment in human cell lines
      derived from the skin (SCL1 and SCL2, squamous cell carcinoma; HaCaT
      keratinocytes; N1 fibroblasts). Using flow cytometry we have determined the
      cellular fluorescence as a marker for the uptake of ATMPn after incubation for 60
      min. Co-staining with ATMPn and fluorescent dyes specific for cell organelles
      reveals an intracellular localization of ATMPn in lysosomes. Following
      irradiation using an incoherent light source (580-740 nm) and a light fluence of
      24 J cm-2, phototoxicity is determined by means of the 3-4.5 dimethylthiazol-2,5
      diphenyl tetrazolium bromide (MTT) assay. For all cell lines ATMPn concentrations
      above 15 nM yield a significant phototoxic effect. The 50% effective
      concentration, EC50, for SCL1 cells is 11.2 +/- 2.9 nM ATMPn. ATMPn uptake and
      phototoxicity are more effective for HaCaT and SCL1 as compared to SCL2 and N1
      cells. Growth curves confirmed the results of the MTT assay. Because of the high
      lysosomal accumulation of ATMPn, already low photosensitizer concentrations
      without dark toxicity yield a high photodynamic effect. Immunofluorescence and
      electron microscopy reveal damage to tonofilaments, plasma membrane and
      mitochondria, indicating a mechanism unrelated to apoptosis. A dose yielding
      complete cell killing, as needed for oncological indications, might lead to
      necrosis, whereas lower sub-lethal doses result in induction of apoptosis.

PMID- 10205876
TI  - Photochemical and pharmacokinetic properties of selected flavins.
AB  - Some photochemical and pharmacokinetic properties of riboflavin, lumiflavin and
      the 2',3',4',5' tetraacetyl, tetrapropionyl, tetrabutiryl and tetrapalmitoyl
      esters of riboflavin have been studied. The esters are considerably more
      photostable than riboflavin but less so than lumiflavin, and appear to be
      photosensitizers with a behaviour similar to that of riboflavin, promoting
      photoreactions of biological targets even in the absence of molecular oxygen. The
      various flavins display important differences in their pharmacokinetic behaviour.
      Riboflavin, lumiflavin and the short-chain esters (the acetyl and propionyl
      esters) are rapidly cleared from serum, and recovered in comparable amounts from
      the liver and kidneys. These results are in agreement with their hydrophilic or
      moderately hydrophobic character. In contrast, the longer-chain butiryl and
      palmitoyl esters exhibit a prolonged retention in serum and undergo a
      significantly larger accumulation in the liver as compared with the kidneys; they
      are also found in the spleen. In all cases the tissue uptake of these esters
      becomes appreciable only after 24 h. These results are coherent with the highly
      hydrophobic character of these esters, which induce a slow release from serum
      lipoproteins and have a preferential clearance via the bile-gut pathway, showing
      affinity for the components of the reticuloendothelial system. These long-chain
      riboflavin esters will probably have a greater and more persistent risk of
      photoinduced hepatotoxicity than riboflavin, lumiflavin and the short-chain
      esters.

PMID- 10205877
TI  - Isomerization of urocanic acid after ultraviolet radiation is influenced by skin
      pigmentation.
AB  - Exposure to ultraviolet (UV) radiation may induce erythema, DNA damage and
      suppression of immune responses. Melanin pigmentation offers protection against
      the first two of these effects, but immunosuppression seems to occur irrespective
      of the subject's pigmentation. Cis-urocanic acid (cis-UCA), produced by
      isomerization of trans-UCA in the stratum corneum on UV exposure, initiates some
      of the immunomodulatory effects of UV radiation. In the present study the
      relationship between skin pigmentation and UCA isomerization has been examined in
      28 healthy individuals of skin types I-IV. Pigmentation is measured in five areas
      of not recently exposed back skin before irradiation with 0, 0.45, 0.9, 1.8 and
      3.6 standard erythema dose (SED) of filtered broadband UV-B (1 SED = 10 mJ cm-2
      at 298 nm). The concentration of UCA isomers is measured immediately after the
      irradiation. With 3.6 SED, the relative production of cis-UCA is close to the
      maximum obtainable, irrespective of skin type. A significant negative correlation
      is found between pigmentation and relative production of cis-UCA at 0.45 and 1.8
      SED, and between pigmentation and absolute production of cis-UCA at 0.45 SED. At
      doses of 0.45 and 0.9 SED the relative and absolute production of cis-UCA are
      higher in the group with skin types I and II when compared with the group with
      skin types III and IV. The higher isomerization in the lightly pigmented subjects
      than in the more pigmented ones may indicate that people with fair skin are at a
      relatively higher risk of immunosuppression when exposed to low doses of UV
      radiation.

PMID- 10205878
TI  - Photodynamic activities of silicon phthalocyanines against achromic M6 melanoma
      cells and healthy human melanocytes and keratinocytes.
AB  - Dichlorosilicon phthalocyanine (Cl2SiPc) and bis(tri-n-hexylsiloxy) silicon
      phthalocyanine (HexSiPc) have been evaluated in vitro as potential
      photosensitizers for photodynamic therapy (PDT) against the human amelanotic
      melanoma cell line M6. Each photosensitizer is dissolved in a solvent-PBS
      mixture, or entrapped in egg-yolk lecithin liposomes or in Cremophor EL micelles.
      The cells are incubated for 1 h with the sensitizer and then irradiated for 20
      min, 1 h or 2 h (lambda > 480 nm, 10 mW cm-2). The photocytotoxic effect is
      dependent on the photosensitizer concentration and the light dose. Higher
      phototoxicity is observed after an irradiation of 2 h: treatment with a solution
      of photosensitizer (2 x 10(-9) M) leads to 10% (HexSiPc in egg-yolk lecithin
      liposomes) or 20% (Cl2SiPc in DMF-PBS solution) cell viability. After 1 h
      incubation and 20 min of light exposure, the photodynamic effect is connected
      with the type of delivery system used. For HexSiPc, lower cell viability is found
      when this photosensitizer is entrapped in egg-yolk lecithin instead of solvent
      PBS or for Cremophor EL micelles with Cl2SiPc. Liposome-delivered HexSiPc leads
      to lipid damage in M6 cells, illustrated by an increase of thiobarbituric acid
      reacting substances (TBARs), but the change is not significant with Cremophor EL.
      The same is observed for the antioxidative defences after photodynamic stress.
      The cells irradiated with HexSiPc entrapped in liposomes display an increase of
      superoxide dismutase (SOD) activity and a decrease of glutathione (GSH) level,
      glutathione peroxidase (GSHPx) and catalase (Cat) activities.

PMID- 10205879
TI  - Fungicidal properties of meso-arylglycosylporphyrins: influence of sugar
      substituents on photoinduced damage in the yeast Saccharomyces cerevisiae.
AB  - A series of neutral meso-arylglycosylporphyrins has been tested in order to
      evaluate their potency as antifungal agents against the yeast Saccharomyces
      cerevisiae. Photodynamic activity of these molecules results in intracellular
      damage as evidenced by the loss of clonogenicity and DNA fragmentation. The
      ability of these photosensitizers to permeate yeast cells is determined by
      microspectrofluorimetry and is correlated with their antifungal potency.
      Amphiphilic porphyrin derivatives are shown to exhibit the more pronounced
      photoactivity.

PMID- 10205880
TI  - Chemiluminescence determination of the in vivo and in vitro antioxidant activity
      of RoseOx and carnosic acid.
AB  - Lipid free-radical oxidation has been studied in vivo in the mitochondrial
      fractions of the liver of rats fed RoseOx (carnosic acid nutritional supplement)
      by measuring chemiluminescence. The kinetics of the lipid chemiluminescence in
      rats fed RoseOx are significantly different from those of the control. The
      intensity of the chemiluminescence fast flash decreases by 45% (p < 0.01), which
      indicates a reduction of lipid peroxides. The time between fast and slow flashes
      increases by 96% (p < 0.05), which indicates a higher content of antioxidants in
      the lipid membrane. The in vitro experiments in rat liver mitochondrial fraction
      display more effective antioxidant action of alpha-tocopherol in 1 microM
      concentration than 1 microM carnosic acid by an increase of the time between fast
      and slow chemiluminescence flashes (p < 0.01). However, the higher antioxidant
      activity of 1 microM carnosic acid by a decrease of intensity of the
      chemiluminescence fast (p < 0.05) and slow (p < 0.05) flashes in comparison with
      alpha-tocopherol is revealed in these experimental conditions in vitro. Carnosic
      acid has antioxidant effects on homogeneous oxidation in vitro as well. The
      chemiluminescence of methyl oleate initiated by 2,2'-azobis(2
      methylpropionitrile) decreases by 25% (p < 0.01) in the presence of 13.5 microM
      carnosic acid. 13.5 microM alpha-tocopherol decreases the methyl oleate
      chemiluminescence by 45%. A higher antioxidant activity of alpha-tocopherol in
      comparison with carnosic acid (p < 0.001) is found in this system. These results
      indicate that RoseOx reduces free-radical-induced lipid peroxidation in vivo. In
      vitro data show that carnosic acid has direct action as an antioxidant, rather
      than as a membrane-structure modifier.

PMID- 10205881
TI  - Penicilliosis marneffei and pythiosis: emerging tropical diseases.
AB  - Penicilliosis marneffei and pythiosis insidiosi are emerging infections in
      subtropical, tropical, and temperate areas of the world. Penicilliosis marneffei
      is endemic in several Southeast Asian countries and may be carried to other areas
      of the world by residents of these countries or visitors. Pythiosis occurs in
      humans and animals who frequent the aquatic habitats that harbor Pythium
      insidiosum. Although early diagnosis is important because of the high morbidity
      or mortality associated with these two diseases, the diagnosis of these
      infections can be difficult because their clinical and histologic features are
      not pathognomonic. Prompt diagnosis is a prerequisite to their appropriate
      treatment. Laboratory testing, involving cultural, histologic and immunologic
      methods, is necessary to establish an unequivocal diagnosis. The clinical
      presentation, epidemiology, diagnosis and treatment of these diseases are
      discussed.

PMID- 10205882
TI  - Experimental aspergillosis in the German cockroach Blattella germanica: a
      histopathological study.
AB  - Inoculation of a spore suspension of Aspergillus flavus in the haemocoel of the
      German cockroach (Blatella germanica) resulted in large-scale invasion of various
      internal organs as seen in tissue sections stained with a fungal stain. The
      organs affected were the alimentary canal, fat bodies, muscle fibres, malpighian
      tubules and the cerebral neurosecretory cells. No invasion of the trachea and
      tracheoles was noted.

PMID- 10205883
TI  - Survey of keratinophilic fungi isolated from city park soils of Pisa, Italy.
AB  - A survey of geophilic dermatophytes and related keratinophilic fungi isolated
      from city park soils of Pisa is reported. Twenty-three (48%) soil samples out of
      48 were positive by hair baiting. The following species were isolated:
      Microsporum gypseum (39%), Trichophyton ajelloi (31%), Chrysosporium
      keratinophilum (14%), T. terrestre (8%), M. fulvum, Ch. luteum, Ch. indicum (5%
      each) and M. cookei (2%). The presence of the different species is discussed in
      relation to the risk of fungal skin infections.

PMID- 10205884
TI  - Experimental Absidia corymbifera infection in rabbits: sequential pathological
      studies.
AB  - Intravenous inoculation of young rabbits with 1.4 x 10(5) spores ml-1 of Absidia
      corymbifera produced gross and microscopic changes principally in the kidneys.
      Grossly, there was congestion, haemorrhages and greyish-white necrotic foci
      giving a mottled appearance to the kidneys. Microscopically, besides congestion
      and haemorrhages, there was a granulomatous reaction characterized by a central
      necrotic mass containing mycelium surrounded by a reactive zone of neutrophils,
      lymphocytes, a few macrophages and giant cells. Fibrous tissue proliferation was
      also present. Characteristic dichotomously branched non-septate fungal hyphae
      could be demonstrated in the sections of kidneys up to 14 days of infection. In
      one rabbit, which had died on the 8th day, small granulomatous lesions with
      fungal hyphae were noticed in the liver's parenchyma.

PMID- 10205885
TI  - Survey of fungal counts and natural occurrence of aflatoxins in Malaysian starch
      based foods.
AB  - In a survey of starch-based foods sampled from retail outlets in Malaysia, fungal
      colonies were mostly detected in wheat flour (100%), followed by rice flour
      (74%), glutinous rice grains (72%), ordinary rice grains (60%), glutinous rice
      flour (48%) and corn flour (26%). All positive samples of ordinary rice and
      glutinous rice grains had total fungal counts below 10(3) cfu/g sample, while
      among the positive rice flour, glutinous rice flour and corn flour samples, the
      highest total fungal count was more than 10(3) but less than 10(4) cfu/g sample
      respectively. However, in wheat flour samples total fungal count ranged from
      10(2) cfu/g sample to slightly more than 10(4) cfu/g sample. Aflatoxigenic
      colonies were mostly detected in wheat flour (20%), followed by ordinary rice
      grains (4%), glutinous rice grains (4%) and glutinous rice flour (2%). No
      aflatoxigenic colonies were isolated from rice flour and corn flour samples.
      Screening of aflatoxin B1, aflatoxin B2, aflatoxin G1 and aflatoxin G2 using
      reversed-phase HPLC were carried out on 84 samples of ordinary rice grains and 83
      samples of wheat flour. Two point four percent (2.4%) of ordinary rice grains
      were positive for aflatoxin G1 and 3.6% were positive for aflatoxin G2. All the
      positive samples were collected from private homes at concentrations ranging from
      3.69-77.50 micrograms/kg. One point two percent (1.2%) of wheat flour samples
      were positive for aflatoxin B1 at a concentration of 25.62 micrograms/kg, 4.8%
      were positive for aflatoxin B2 at concentrations ranging from 11.25-252.50
      micrograms/kg, 3.6% were positive for aflatoxin G1 at concentrations ranging from
      25.00-289.38 micrograms/kg and 13.25% were positive for aflatoxin G2 at
      concentrations ranging from 16.25-436.25 micrograms/kg. Similarly, positive wheat
      flour samples were mostly collected from private homes.

PMID- 10205886
TI  - Effects of Fusarium moniliforme culture extracts and fumonisin B1 on DNA, RNA and
      protein synthesis by baby hamster kidney cells.
AB  - Baby hamster kidney cells (BHK-21) were exposed to culture filtrates of 4
      Fusarium moniliforme isolates containing varying levels of fumonisin B1 (FMB1)
      and the effects upon RNA, DNA and protein synthesis were monitored. Cells were
      also grown on medium amended with FMB1 only for comparison. After 24 h incubation
      FMB1 (100 micrograms/100 ml medium) reduced protein synthesis by 4% and by 18%
      after 48 h. Culture filtrates containing the highest levels of FMB1 also caused
      the greatest inhibition in protein synthesis after 24 h but after 48 h protein
      synthesis levels were the same as controls even though the FMB1 level was 360
      micrograms/100 ml. Only FMB1 reduced DNA synthesis, by 8% after 24 h but after 48
      h DNA levels had increased by 40% over controls. The culture filtrates containing
      the highest levels of FMB1 (360 micrograms/100 ml) reduced DNA synthesis more
      than 50% after 24 h and 48 h. Culture filtrates containing lesser amounts of FMB1
      in some instances stimulated DNA synthesis and inhibited it in others. There was
      also no correlation in the level of FMB1 with the inhibition of RNA synthesis by
      BHK cells. It appears that metabolites other than fumonisin produced by F.
      moniliforme in culture can affect and both stimulate and inhibit RNA, DNA and
      protein synthesis by BHK cells.

PMID- 10205887
TI  - Fine needle aspiration in the diagnosis of pulmonary paracoccidioidomycosis.
AB  - Six cases of pulmonary paracoccidioidomycosis diagnosed only by transthoracic
      fine needle aspiration are presented. The clinical and radiological presentation
      is varied. The most frequent use of this technique will permit the diagnosis of
      early lesions of mycosis.

PMID- 10205888
TI  - The gene that determines resistance to tioconazole and to acridine derivatives in
      Aspergillus nidulans may have a corresponding gene in Trichophyton rubrum.
AB  - Understanding the genetic mechanisms involved in resistance to antifungal agents
      is important in the fight against pathogenic fungi. In the present investigation
      we studied a strain of the model fungus Aspergillus nidulans which presents
      resistance to tioconazole and behaves as the wild strain in the presence of other
      azole derivatives. Genetic analysis revealed that this resistance is due to a
      mutation in a single gene located on chromosome II, closely linked to the allele
      responsible for resistance to acriflavine and other acridine derivatives, i.e.,
      acrA1. This result suggests that a multidrug resistance (MDR)-type mechanisms may
      be involved. Two tioconazole-resistant strains of the pathogenic fungus
      Trichophyton rubrum obtained after mutagenic treatment also became simultaneously
      resistant to acriflavine and ethidium bromide, suggesting the existence of a
      resistance mechanism similar to that observed with the acrA1 mutation in A.
      nidulans.

PMID- 10205889
TI  - Degradation of chicken feathers by Chrysosporium georgiae.
AB  - Using a baiting technique, Chrysosporium georgiae was isolated from chicken
      feathers. Twenty-eight different fungal isolates were evaluated for their ability
      to produce keratinase enzymes using a keratin-salt agar medium containing either
      white chicken feathers or a prepared feather keratin suspension (KS). The
      Chrysosporium species were able to use keratin and grow at different rates.
      Chrysosporium georgiae completely degraded the added keratin after 9 days of
      incubation. Degradation of feathers by C. georgiae was affected by several
      cultural factors. Highest keratinolytic activity occurred after 3 weeks of
      incubation at 6 and 8 pH at 30 degrees C. Chrysosporium georgiae was able to
      degrade white chicken feathers, whereas bovine and human hair and sheep wool were
      not degraded and did not support fungal growth. Addition of 1% glucose to the
      medium containing keratin improved fungal growth and increased enzyme production.
      Higher keratin degradation resulted in high SH accumulation and the utilization
      of the carbohydrate carbon in the medium resulted in high keto-acid accumulation
      but decreased ammonia accumulation. Supplementation of the keratin-salt medium
      with minerals such as NH4Cl and MgSO4 slightly increased mycelial growth, but
      decreased production of extracellular keratinase. Keratinase enzymes were very
      poorly produced in the absence of keratin, indicating its inducible nature.
      Analysis of endocellular keratinases in the mycelial homogenate indicated higher
      activity of intracellular keratinase as compared to the extracellular enzyme in
      culture filtrates. Chrysosporium georgiae was the most superior for keratinase
      production among the Chrysosporium species tested in the presence or absence of
      glucose. It produced more of the intracellular enzymes than the exocellular ones.

PMID- 10205890
TI  - The effects of four mycotoxins on the mitogen stimulated proliferation of bovine
      peripheral blood mononuclear cells in vitro.
AB  - The effects of four mycotoxins, T-2 toxin, deoxynivalenol (DON), ochratoxin A
      (OTA) and fumonisin B1 (FB1) on the response of bovine peripheral blood
      mononuclear cells (PBM) in vitro to the mitogens concanavalin A (Con A),
      phytohaemagglutinin A (PHA) and pokeweed mitogen (PWM) were assayed after 4 days'
      incubation using 3H-thymidine uptake and the MTT bioassay. The concentrations of
      mycotoxin required to reduce the proliferative response of PBM by 50% for Con A,
      PHA and PWM as measured by 3H-thymidine incorporation was for T-2 toxin 0.30,
      0.40 and 0.18 ng ml-1; for DON 0.07, 0.09 and 0.04 microgram ml-1; for OTA 0.10,
      0.20 and 0.15 microgram ml-1, and for FB1 35, 18 and 11 micrograms ml-1
      respectively. The concentrations of mycotoxin required to reduce the
      proliferative response of PBM by 50% for Con A, PHA and PWM as measured by the
      MTT bioassay were for T-2 toxin 2.0, 2.0 and 1.0 mg ml-1; for DON 0.70, 0.50 and
      0.50 microgram ml-1; OTA 1.5, 1.5 and 1.5 micrograms ml-1; and FB1 > 50, > 50 and
      20 micrograms ml-1 respectively. Further cytotoxicity assays including the LDH
      bioassay and Trypan blue exclusion were performed only on Con A-stimulated PBM
      cells after 72 h incubation. With the LDH-bioassay the 50% inhibition levels were
      T-2 toxin 0.3 ng ml-1, DON 0.4 microgram ml-1, OTA 1.4 micrograms ml-1 and FB1
      3.5 micrograms ml-1; for Trypan blue uptake the 50% inhibition levels were T-2
      toxin 5 ng ml-1, DON 2.3 micrograms ml-1 and OTA 4 micrograms ml-1 respectively.

PMID- 10205891
TI  - Fusarium species from plant debris associated with soils from maize production
      areas in the Transkei region of South Africa.
AB  - Fusarium species were isolated from plant debris in soil samples collected from
      cultivated maize fields and from undisturbed grasslands in two areas of the
      Transkei region. A total of 1205 Fusarium isolates were recovered from 27 soil
      samples. Fifteen Fusarium species were recovered from plant debris from Bizana
      soils and 13 Fusarium species from plant debris from Centane soils. The two
      dominant Fusarium species in both areas were F. oxysporum and F. equiseti. Very
      few isolates of F. moniliforme and F. subglutinans were recovered, but both of
      these species had significantly higher relative densities in cultivated soils
      than in undisturbed soils.

PMID- 10205892
TI  - Molecular cloning and functional expression of O-methyltransferases common to
      isoquinoline alkaloid and phenylpropanoid biosynthesis.
AB  - In cell suspension cultures of the meadow rue Thalictrum tuberosum, biosynthesis
      of the anti-microbial alkaloid berberine can be induced by addition of methyl
      jasmonate to the culture medium. The activities of the four methyltransferases
      involved in the formation of berberine from L-tyrosine are increased in response
      to elicitor addition. Partial clones generated by RT-PCR with methyltransferase
      specific primers were used as hybridization probes to isolate four cDNAs encoding
      O-methyltransferases from a cDNA library prepared from poly(A)+ RNA isolated from
      methyl jasmonate-induced cell suspension cultures of T. tuberosum. RNA gel blot
      hybridization indicated that the transcripts for the methyltransferases
      accumulated in response to addition of methyl jasmonate to the cell culture
      medium. The cDNAs were functionally expressed in Spodoptera frugiperda Sf9 cells
      and were shown to have varying and broad substrate specificities. A difference of
      a single amino acid residue between two of the enzymes was sufficient to alter
      the substrate specificity. The four cDNAs were expressed either as four
      homodimers or as six heterodimers by co-infection with all possible combinations
      of the four recombinant baculoviruses. These 10 isoforms thus produced displayed
      distinct substrate specificities and in some cases co-infection with two
      different recombinant baculoviruses led to the O-methylation of new substrates.
      The substrates that were O-methylated varied in structural complexity from simple
      catechols to phenylpropanoids, tetrahydrobenzylisoquinoline, protoberberine and
      tetrahydrophenethylisoquinoline alkaloids, suggesting that some biosynthetic
      enzymes may be common to both phenylpropanoid and alkaloid anabolism.

PMID- 10205893
TI  - Regulation of carotenoid biosynthesis during tomato fruit development: expression
      of the gene for lycopene epsilon-cyclase is down-regulated during ripening and is
      elevated in the mutant Delta.
AB  - The red colour of tomato (Lycopersicon esculentum) fruits is provided by the
      carotenoid pigment lycopene whose concentration increases dramatically during the
      ripening process. A single dominant gene, Del, in the tomato mutant Delta changes
      the fruit colour to orange as a result of accumulation of delta-carotene at the
      expense of lycopene. The cDNA for lycopene epsilon-cyclase (CrtL-e), which
      converts lycopene to delta-carotene, was cloned from tomato. The primary
      structure of CRTL-E is 71% identical to the homologous polypeptide from
      Arabidopsis and 36% identical to the tomato lycopene beta-cyclase, CRTL-B. The
      CrtL-e gene was mapped to a single locus on chromosome 12 of the tomato linkage
      map. This locus co-segregated with the Del gene. In the wild-type tomato, the
      transcript level of CrtL-e decreases at the 'breaker' stage of ripening to a non
      detectable level in the ripe fruit. In contrast, it increases approximately 30
      fold during fruit ripening in the Delta plants. The Delta mutation does not
      affect carotenoid composition nor the mRNA level of CrtL-e in leaves and flowers.
      These results strongly suggest that the mutation Del is an allele of the gene for
      epsilon-cyclase. Together with previous data, our results indicate that the
      primary mechanism that controls lycopene accumulation in tomato fruits is based
      on the differential regulation of expression of carotenoid biosynthesis genes.
      During fruit development, the mRNA levels for the lycopene-producing enzymes
      phytoene synthase (PSY) and phytoene desaturase (PDS) increase, while the mRNA
      levels of the genes for the lycopene beta- and epsilon-cyclases, which convert
      lycopene to either beta- or delta-carotene, respectively, decline and completely
      disappear.

PMID- 10205894
TI  - An Arabidopsis mutant with deregulated ABA gene expression: implications for
      negative regulator function.
AB  - The physiological acclimation of plants to osmotic stresses involves a complex
      programme of gene regulation. In one signalling pathway, elevated levels of
      abscisic acid (ABA) activate a subset of stress genes. Because ABA responses lack
      a definable morphological phenotype, we have screened for mutants that exhibit
      deregulated ABA-responsive gene expression. To monitor this ABA response, a line
      of Arabidopsis thaliana carrying a transgene composed of the ABA-responsive
      Arabidopsis kin2 promoter fused to the coding sequence for the firefly luciferase
      gene, kin2::luc, was generated. Patterns of ABA-responsive luciferase activity
      were monitored by photon counting. In contrast to wild-type plants which display
      a transient activation of kin2::luc, an ABA deregulated gene expression mutant
      (ade1) exhibits both sustained and enhanced levels of transgene activity. Levels
      of kin2, cor47 and rab18 expression in ade1 plants are also enhanced and
      prolonged indicating that the molecular mechanism(s) altered in ade1 plants
      affects the regulation of other ABA-responsive genes. The mutant phenotype is
      specific for the ABA response as cold-inducible kin2 expression is unaltered in
      ade1 plants. Genetic analyses indicate that the ade1 mutant is a monogenic
      recessive trait. A role for negative regulator function in ABA signalling is
      discussed.

PMID- 10205895
TI  - The Arabidopsis HAL2-like gene family includes a novel sodium-sensitive
      phosphatase.
AB  - The yeast HAL2 gene encodes a lithium- and sodium-sensitive phosphatase that
      hydrolyses 3'-phosphoadenosine-5'-phosphate (PAP). Salt toxicity in yeast results
      from Hal2 inhibition and accumulation of PAP, which inhibits sulphate
      assimilation and RNA processing. We have investigated whether the model plant
      Arabidopsis thaliana contains sodium-sensitive PAP phosphatases. The Arabidopsis
      HAL2-like gene family is composed of three members: AtAHL and AtSAL2,
      characterized in the present work, and the previously identified AtSAL1. The
      AtAHL and AtSAL2 cDNAs complement the auxotrophy for methionine of the yeast hal2
      mutant and the recombinant proteins catalyse the conversion of PAP to AMP in a
      Mg(2+)-dependent reaction sensitive to inhibition by Ca2+ and Li+. The PAP
      phosphatase activity of AtAHL is sensitive to physiological concentrations of
      Na+, whereas the activities of AtSAL1 and AtSAL2 are not. Another important
      difference is that AtAHL is very specific for PAP while AtSAL1 and AtSAL2 also
      act as inositol polyphosphate 1-phosphatases. AtAHL constitutes a novel type of
      sodium-sensitive PAP phosphatase which could act co-ordinately with plant
      sulphotransferases and serve as target of salt toxicity in plants.

PMID- 10205896
TI  - Glyoxalase I from Brassica juncea: molecular cloning, regulation and its over
      expression confer tolerance in transgenic tobacco under stress.
AB  - Despite its ubiquitous presence, the role of glyoxalase I has not been well
      investigated in plants. In order to find out its physiological functions, we have
      cloned and characterized a cDNA from Brassica juncea encoding glyoxalase I (Gly
      I) and made transgenic tobacco plants harbouring Gly I in both sense and
      antisense orientation. The transgenic nature of the plants was confirmed by
      Southern blotting, and the estimated number of genes inserted ranged from one to
      six. The transcript and protein levels of glyoxalase I were also monitored in
      transgenic plants. The expression of glyoxalase I in B. juncea was upregulated in
      response to salt, water and heavy metal stresses. In response to a high
      concentration of salt, the transcript level averaged threefold higher in 72 h,
      and an increase in the protein was also seen by immunoblotting. The transgenic
      plants over-expressing glyoxalase I showed significant tolerance to methylglyoxal
      and high salt, as tested in detached leaf disc senescence assay. A comparison of
      plants expressing high and low levels of glyoxalase I showed that the tolerance
      to different salt concentrations was correlated with the degree of glyoxalase I
      expression. Our results suggest an important role of glyoxalase I in conferring
      tolerance to plants under stress conditions.

PMID- 10205897
TI  - Site-directed mutagenesis of serine 158 demonstrates its role in spinach leaf
      sucrose-phosphate synthase modulation.
AB  - Site-directed mutagenesis of spinach sucrose-phosphate synthase (SPS) was
      performed to investigate the role of Ser158 in the modulation of spinach leaf
      SPS. Tobacco plants expressing the spinach wild-type (WT), S158A, S158T and
      S157F/S158E SPS transgenes were produced. Expression of transgenes appeared not
      to reduce expression of the tobacco host SPS. SPS activity in the WT and the
      S158T SPS transgenics showed light/dark modulation, whereas the S158A and
      S157F/S158E mutants were not similarly light/dark modulated: the S158A mutant
      enzyme was not inactivated in the dark, and the S157F/S158E was not activated in
      the light. The inability to modulate the activity of the S158A mutant enzyme by
      protein phosphorylation was demonstrated in vitro. The WT spinach enzyme
      immunopurified from dark transgenic tobacco leaves had a low initial activation
      state, and could be activated by PP2A and subsequently inactivated by SPS-kinase
      plus ATP. Rapid purification of the S158A mutant enzyme from dark leaves of
      transgenic plants using spinach-specific monoclonal antibodies yielded enzyme
      that had a high initial activation state, and pre-incubation with leaf PP2A or
      ATP plus SPS-kinase (the PKIII enzyme) caused little modulation of activity. The
      results demonstrate the regulatory significance of Ser158 as the major site
      responsible for dark inactivation of spinach SPS in vivo, and indicate that the
      significance of phosphorylation is the introduction of a negative charge at the
      Ser158 position.

PMID- 10205898
TI  - Intimate association of microsatellite repeats with retrotransposons and other
      dispersed repetitive elements in barley.
AB  - Simple sequence repeat (SSR)-based genetic markers are being actively developed
      for the majority of crop plant species. In barley, characterization of 290
      dinucleotide repeat-containing clones from SSR-enriched libraries has revealed
      that a high percentage are associated with cereal retrotransposon-like and other
      dispersed repetitive elements. Associations found were with BARE-1, WIS2-1A,
      PREM1 and the dispersed repetitive element R173. Additional similarities between
      different SSR clones, which have no matches in DNA sequence databases, indicate
      that this phenomenon is probably widespread in the barley genome. Sequence
      homologies to the non-coding regions of several cereal genes were also explained
      by homology to mobile genetic elements. The SSRs found can therefore be
      classified into two types: (1) those with unique sequences on either flank, and
      (2) those which are intimately associated with retro-transposons and other
      dispersed repetitive elements. As the cereal genome is thought to consist largely
      of this type of DNA, some random association would be expected. However, the
      conserved positions of the SSRs, relative to repetitive elements, indicate that
      they have arisen non-randomly. Furthermore, this class of SSRs can be classified
      into three subtypes: (1) those which are positioned 3' of a transposable element
      with unique sequence on the other flank, (2) those positioned 5' of a
      transposable element, and (3) those which have arisen from an internal sequence
      and so have transposable element sequence on both flanks. The first appear to be
      analogous to the class of SSRs in mammalian systems which are associated with Alu
      elements and SINEs (short interspersed elements) and which have been postulated
      to arise following integration of an extended and polyadenylated retro-transcript
      into the host genome, followed by mutation of the poly(A) tract and expansion
      into an SSR. For the second, we postulate that a proto-SSR (A-rich sequence) has
      acted as a 'landing pad' for transposable element insertion (rather than being
      the result of insertion), while the third includes those which have evolved as a
      component of an active transposable element which has spread throughout the
      genome during bursts of transposition activity. The implications of these
      associations for genome and SSR evolution in barley are discussed.

PMID- 10205899
TI  - Characterization of the ABA-deficient tomato mutant notabilis and its
      relationship with maize Vp14.
AB  - The notabilis (not) mutant of tomato has a wilty phenotype due to a deficiency in
      the levels of the plant hormone abscisic acid (ABA). The mutant appears to have a
      defect in a key control step in ABA biosynthesis--the oxidative cleavage of a 9
      cis xanthophyll precursor to form the C15 intermediate, xanthoxin. A maize
      mutant, viviparous 14 (vp14) was recently obtained by transposon mutagenesis.
      This maize genetic lesion also affects the oxidative cleavage step in ABA
      synthesis. Degenerate primers for PCR, based on the VP14 predicted amino acid
      sequence, have been used to provide probes for screening a wilt-related tomato
      cDNA library. A full-length cDNA clone was identified which is specific to the
      not gene locus. The ORFs of the tomato cDNA and maize Vp14 are very similar,
      apart from parts of their N-terminal sequences. The not mutation has been
      characterized at the DNA level. A specific A/T base pair deletion of the coding
      sequence has resulted in a frameshift mutation, indicating that not is a null
      mutant. This observation is discussed in connection with the relatively mild
      phenotype exhibited by not mutant homozygotes.

PMID- 10205900
TI  - Regional insertional mutagenesis of genes on Arabidopsis thaliana chromosome V
      using the Ac/Ds transposon in combination with a cDNA scanning method.
AB  - For regional insertional mutagenesis of Arabidopsis thaliana genes, we combined a
      cDNA scanning method (Hayashida et al. Gene 1995; 165:155-161) and an Ac/Ds
      transposon designed for local mutagenesis, and evaluated this approach with two
      overlapping yeast artificial chromosome (YAC) clones, CIC7E11 and CIC8B11, on A.
      thaliana chromosome 5. We applied a previously developed novel cDNA selection
      method using DNA latex particles (cDNA scanning method) to the two YAC clones and
      constructed two sub-libraries in which cDNAs for genes on each YAC DNA were
      concentrated. From each sub-library we isolated cDNAs for genes on each YAC DNA,
      partially sequenced them, and produced expressed sequence tags (ESTs). In total,
      113 non-redundant groups of cDNAs were obtained. Forty-four per cent of these EST
      clones were novel, and 34% had significant homology to functional proteins from
      various organisms. In parallel, we transposed Ds from a donor Ds-GUS-T-DNA line,
      Ds4391-20, already mapped to the CIC7E11/8B11 region. We obtained Ds-transposed
      lines and recovered their Ds-flanking genomic DNAs by thermal asymmetric
      interlaced (TAIL) polymerase chain reaction (PCR). Dot-blot analysis indicated
      that 20% of the lines contained transposed Ds in the CIC7E11/8B11 region,
      suggesting that this Ac/Ds transposon system is effective for regional
      insertional mutagenesis. To isolate Ds insertion mutants in the genes identified
      from the CIC7E11/8B11 region, we carried out PCR screening from 800 Ds-containing
      lines using Ds-specific and gene-specific primers that were designed from the 113
      cDNA sequences identified by the cDNA scanning method. We found that 49 lines
      contain Ds insertion mutations, and that five lines contain Ds mutations in genes
      that are mapped to the sequenced CIC7E11/8B11 genomic DNA region. These results
      indicate that combining the cDNA scanning method and the Ac/Ds transposon gives a
      powerful tool for regional insertional mutagenesis not only in Arabidopsis but
      also in other plants or crops whose genomes are not sequenced.

PMID- 10205901
TI  - Map positions of SFR genes in relation to other freezing-related genes of
      Arabidopsis thaliana.
AB  - We determined the map positions of seven SFR genes and compared them to the
      positions of 51 genes suspected of involvement in freezing tolerance in
      Arabidopsis thaliana. The SFR genes were recognized by the freezing sensitivity
      of mutants; the others (including 14 whose map positions we have determined) were
      genes whose expression is induced by low temperature, genes involved in abscisic
      acid (ABA) biosynthesis and perception, and genes involved in tolerance of
      oxidative stress. The comparison of map positions indicated a limited set of
      potential identities, some of which were eliminated by further mapping or by an
      allelism test.

PMID- 10205902
TI  - Self-processing 2A-polyproteins--a system for co-ordinate expression of multiple
      proteins in transgenic plants.
AB  - Achieving co-ordinate, high-level and stable expression of multiple transgenes in
      plants is currently difficult. Expression levels are notoriously variable and
      influenced by factors that act independently on transgenes at different genetic
      loci. Instability of expression due to loss, re-arrangement or silencing of
      transgenes may occur, and is exacerbated by increasing numbers of transgenic loci
      and repeated use of homologous sequences. Even linking two or more genes within a
      T-DNA does not necessarily result in co-ordinate expression. Linking proteins in
      a single open reading frame--a polyprotein--is a strategy for co-ordinate
      expression used by many viruses. After translation, polyproteins are processed
      into constituent polypeptides, usually by proteinases encoded within the
      polyprotein itself. However, in foot-and-mouth disease virus (FMDV), a sequence
      (2A) of just 16-20 amino acids appears to have the unique capability to mediate
      cleavage at its own C-terminus by an apparently enzyme-independent, novel type of
      reaction. This sequence can also mediate cleavage in a heterologous protein
      context in a range of eukaryotic expression systems. We have constructed a
      plasmid in which the 2A sequence is inserted between the reporter genes
      chloramphenicol acetyltransferase (CAT) and beta-glucuronidase (GUS), maintaining
      a single open reading frame. Here we report that expression of this construct in
      wheatgerm lysate and transgenic plants results in efficient cleavage of the
      polyprotein and co-ordinate expression of active CAT and GUS. Self-processing
      polyproteins using the FMDV 2A sequence could therefore provide a system for
      ensuring co-ordinated, stable expression of multiple introduced proteins in plant
      cells.

PMID- 10205903
TI  - Chloroplast Cpn20 forms a tetrameric structure in Arabidopsis thaliana.
AB  - Chloroplast chaperonin 20 (Cpn20) in higher plants is a functional homologue of
      the Escherichia coli GroES, which is a critical regulator of chaperonin-mediated
      protein folding. The cDNA for a Cpn20 homologue of Arabidopsis thaliana was
      isolated. It was 958 bp long, encoding a protein of 253 amino acids. The protein
      was composed of an N-terminal chloroplast transit peptide, and the predicted
      mature region comprised two distinct GroES domains that showed 42% amino acid
      identity to each other. The isolated cDNA was constitutively expressed in
      transgenic tobacco. Immunogold labelling showed that Cpn20 is accumulated in
      chloroplasts of transgenic tobacco. A Northern blot analysis revealed that mRNA
      for the chloroplast Cpn20 is abundant in leaves and is increased by heat
      treatment. To examine the oligomeric structure of Cpn20, a histidine-tagged
      construct lacking the transit peptide was expressed in E. coli and purified by
      affinity chromatography. Gel-filtration and cross-linking analyses showed that
      the expressed products formed a tetramer. The expressed products could substitute
      for GroES to assist the refolding of citrate synthase under non-permissive
      conditions. The analysis on the subunit stoichiometry of the GroEL-Cpn20 complex
      also revealed that the functional complex is composed of a GroEL tetradecamer and
      a Cpn20 tetramer.

PMID- 10205904
TI  - Post-transcriptional and developmental regulation of a CMS-associated
      mitochondrial gene region by a nuclear restorer gene.
AB  - Transcripts of the mitochondrial gene region orf224/atp6, which is associated
      with the Polima or pol cytoplasmic male sterility (CMS) of Brassica napus, differ
      among fertile, sterile and nuclear-restored plants. We show here that the effects
      of the restorer gene Rfp on orf224/atp6 transcripts varies among different floral
      organs. Relative to monocistronic atp6 transcripts, levels of the dicistronic
      transcripts spanning orf224 and atp6 are dramatically reduced in petals, stamens
      and carpels, but not sepals, of restored flowers. In pol CMS plants, the relative
      levels of different orf224/atp6 transcripts are similar among the floral organs.
      Analysis of guanylyltransferase-labeled mtRNA indicates that only the dicistronic
      2.2 and 1.9 kb orf224/atp6 transcripts carry an initiator 5' terminus; hence the
      1.4 and 1.3 kb transcripts of restored plants, as well as the 1.1 kb atp6
      transcript common to all genotypes, are generated by RNA processing and not de
      novo initiation. Although steady-state levels of dicistronic transcripts in
      flower buds are lower in restored than in sterile plants, run-on transcription
      experiments show that these transcripts are synthesized at the same rate in both
      types of flowers. These findings imply that the restorer gene acts by
      conditioning the removal of sequences from the 5' end of dicistronic transcripts
      in a developmentally regulated manner. Run-on transcription experiments indicate
      that the single 1.1 kb atp6 transcript of nap cytoplasm is also generated by
      removal of sequences from the 5' end of a precursor. We suggest that specific
      endonucleolytic cleavage of a precursor RNA, followed by non-specific 3' to 5'
      exonuclease action, may represent a common mechanism for tailoring transcripts in
      plant mitochondria.

PMID- 10205905
TI  - Functional complementation of yeast vma1 delta cells by a plant subunit A homolog
      rescues the mutant phenotype and partially restores vacuolar H(+)-ATPase
      activity.
AB  - The ability of a vacuolar H(+)-ATPase (V-ATPase) subunit homolog (subunit A) from
      plants to rescue the vma mutant phenotype of yeast was investigated as a first
      step towards investigating the structure and function of plant subunits in
      molecular detail. Heterologous expression of cotton cDNAs encoding near-identical
      isoforms of subunit A in mutant vma1 delta yeast cells successfully rescued the
      mutant vma phenotype, indicating that subunit A of plants and yeast have retained
      elements essential to V-ATPases during the course of evolution. Although vacuoles
      become acidified, the plant-yeast hybrid holoenzyme only partially restored V
      ATPase activity (approximately 60%) in mutant yeast cells. Domain substitution of
      divergent N- or C-termini only slightly enhanced V-ATPase activity, whereas
      swapping both domains acted synergistically, increasing coupled ATP hydrolysis
      and proton translocation by approximately 22% relative to the native plant
      subunit. Immunoblot analysis indicated that similar amounts of yeast, plant or
      plant-yeast chimeric subunits are membrane-bound. These results suggest that
      subunit A terminal domains contain structural information that impact V-ATPase
      structure and function.

PMID- 10205906
TI  - Lesion mimic mutants of rice with alterations in early signaling events of
      defense.
AB  - We screened 93 lesion mimic mutants of rice for resistance to the blast fungus,
      Magnaporthe grisea, and found eight mutants that exhibited significant resistance
      to the fungus. We called these mutants cdr (cell death and resistance) and
      further analyzed three of them. Two mutations, cdr1 and cdr2, were recessive and
      one, Cdr3, was dominant. Many small brownish lesions developed over the entire
      leaf of the mutants 20-50 days after sowing. TUNEL staining revealed that DNA
      fragmentation occurred in leaf blade cells of the homozygous Cdr3 mutants.
      Autofluorescence and callose deposition were visible in leaf cells of these three
      mutants. Activation of two defense-related genes, PBZ1 and PR1, was observed in
      the leaves of the mutants; high expression of PBZ1 was correlated with the lesion
      formation in the three mutants, whereas PR1 was constitutively expressed in the
      cdr2 and Cdr3 mutants irrespective of the lesion formation. Levels of momilactone
      A, a major phytoalexin of rice, in these mutants were increased approximately 100
      400-fold relative to the wild-type levels. Suspension-cultured cells of the cdr1
      and cdr2 but not Cdr3 produced higher levels of H2O2 than the wild type when
      treated with calyculin A, an inhibitor of protein phosphatase 1. These results
      suggest that biochemical lesions of cdr1 and cdr2 lie in the early signaling
      steps leading to activation of the NADPH oxidase and that type-1 protein
      phosphatase is operative in protein dephosphorylation involved in NADPH oxidase
      activation.

PMID- 10205907
TI  - Modification of gibberellin production and plant development in Arabidopsis by
      sense and antisense expression of gibberellin 20-oxidase genes.
AB  - Gibberellin (GA) 20-oxidase catalyses consecutive steps late in GA biosynthesis
      in plants. In Arabidopsis, the enzyme is encoded by a gene family of at least
      three members (AtGA20ox1, AtGA20ox2 and AtGA20ox3) with differential patterns of
      expression. The genes are regulated by feedback from bioactive GAs, suggesting
      that the enzymes may be involved in regulating GA biosynthesis. To investigate
      this, we produced transgenic Arabidopsis expressing sense or antisense copies of
      each of the GA 20-oxidase cDNAs. Over-expression of any of the cDNAs gave rise to
      seedlings with elongated hypocotyls; the plants flowered earlier than controls in
      both long and short days and were 25% taller at maturity. GA analysis of the
      vegetative rosettes showed a two- to threefold increase in the level of GA4,
      indicating that GA 20-oxidase normally limits bioactive GA levels. Plants
      expressing antisense copies of AtGA20ox1 had short hypocotyls and reduced rates
      of stem elongation. This was reflected in reduced levels of GA4 in both rosettes
      and shoot tips. In short days, flowering was delayed and the reduction in the
      rate of stem elongation was greater. Antisense expression of AtGA20ox2 had no
      apparent effects in long days, but stem growth in one transgenic line grown in
      short days was reduced by 20%. Expression of antisense copies of AtGA20ox3 had no
      visible effect, except for one transgenic line that had short hypocotyls. These
      results demonstrate that GA levels and, hence, plant growth and development can
      be modified by manipulation of GA 20-oxidase expression in transgenic plants.

PMID- 10205908
TI  - Green fluorescent protein as a marker to investigate targeting of organellar RNA
      polymerases of higher plants in vivo.
AB  - The recent identification of phage-type RNA polymerases encoded in the nuclear
      genome of higher plants has provided circumstantial evidence for functioning of
      these polymerases in the transcription of the mitochondrial and plastid genomes,
      as demonstrated by sequence analysis and in vitro import experiments. To
      determine the subcellular localization of the phage-type organellar RNA
      polymerases in plants, the putative transit peptides of the RNA polymerases
      RpoT;1 and RpoT;3 from Arabidopsis thaliana and RpoT from Chenopodium album were
      fused to the coding sequence of a green fluorescent protein (GFP). The constructs
      were used to stably transform A. thaliana. Transgenic plants were examined for
      green fluorescence with epifluorescence and confocal laser scanning microscopy.
      Plants expressing the GFP fusions under control of the CaMV35S promoter exhibited
      a distinct subcellular localization of the GFP fluorescence for each of the
      fusion constructs. In plants expressing GFP fusions with the putative transit
      peptides of ARAth;RpoT;1 and CHEal;RpoT, fluorescence was found exclusively in
      mitochondria, both in root and leaf cells. In contrast, GFP fluorescence in
      plants expressing the ARAth;RpoT;3-GFP construct accumulated in chloroplasts of
      leaf cells and nongreen plastids (leucoplasts) of root cells. By demonstrating
      targeting in plants, the data add substantial evidence for the phage-type RNA
      polymerases from C. album and A. thaliana to function in the transcriptional
      machinery of mitochondria and plastids.

PMID- 10205909
TI  - Regulation of a putative high-affinity nitrate transporter (Nrt2;1At) in roots of
      Arabidopsis thaliana.
AB  - Putative high-affinity nitrate (NO3-) transporter genes, designated Nrt2;1At and
      Nrt2;2At, were isolated from Arabidopsis thaliana by RT-PCR using degenerate
      primers. The genes shared 86% and 89% identity at the amino acid and nucleotide
      levels, respectively, while their proteins shared 30-73% identities with other
      eukaryotic high-affinity NO3- transporters. Both genes were induced by NO3-, but
      Nrt2;1At gene expression was not apparent in 2- and 5-day-old plants. By 10 days,
      and thereafter, Nrt2;1At gene expression in roots was substantially higher than
      for the Nrt2;2At gene. Root Nrt2;1At expression levels were strongly correlated
      with inducible high-affinity 13NO3- influx into intact roots under several
      treatment conditions. The use of inhibitors of N assimilation indicated that
      downregulation of Nrt2;1At expression was mediated by NH4+, gln and other amino
      acids.

PMID- 10205910
TI  - Potato StubSNF1 interacts with StubGAL83: a plant protein kinase complex with
      yeast and mammalian counterparts.
AB  - StubSNF1 is a potato cDNA that encodes a protein kinase similar to the yeast SNF1
      gene involved in transcriptional regulation of glucose-repressible genes. The
      yeast SNF1 functions in a complex with GAL83/SIP1/SIP2 and SNF4 proteins. We have
      used StubSNF1 as bait in a yeast two-hybrid system to screen for potato cDNAs
      encoding proteins that bind to StubSNF1. Three overlapping cDNAs, two different
      in size, were isolated. DNA sequence analysis revealed that they were orthologues
      of the yeast GAL83/SIP1/SIP2 genes and their mammalian counterparts, AMPK beta
      subunits. The direct interaction between the potato proteins StubGAL83 and
      StubSNF1 was shown by an in vitro binding assay. Southern and Northern
      hybridisations revealed that StubGAL83 exists in a low copy number in the potato
      genome and is highly (but organ-specifically) expressed in potato. In contrast,
      StubSNF1 possesses low transcript levels in each organ, except in flowers where
      high amounts of StubSNF1 mRNA could be detected. We demonstrate here that
      StubGAL83 can also interact with yeast SNF4 in a yeast two-hybrid system
      suggesting that plant SNF1 kinases may function in complexes similar to those
      detected in yeast and mammals.

PMID- 10205911
TI  - Dissection of the ozone-induced calcium signature.
AB  - The cellular responses of plants to numerous extracellular stimuli are mediated
      by transient elevations in the concentration of cytosolic free calcium
      ([Ca2+]cyt). We have addressed the question of how cells can use this apparently
      ubiquitous system to initiate so many specific and appropriate end responses. We
      show that the pollutant gas ozone elicits a biphasic Ca2+ response in intact
      Arabidopsis plants and a subsequent increase in expression of the gene encoding
      the antioxidant defence enzyme glutathione-S-transferase (GST). The second of the
      two [Ca2+]cyt peaks, but not the first, could be eliminated either by pre
      treatment of plants with lanthanum chloride, or by reducing the duration of ozone
      fumigation. Under these conditions, ozone-induced GST expression was abolished.
      These data provide a functional dissection of the ozone Ca2+ signalling pathway
      and indicate that the second ozone-induced [Ca2+]cyt peak provides the necessary
      information to direct expression of GST.

PMID- 10205912
TI  - Digital mapping of bacterial artificial chromosomes by fluorescence in situ
      hybridization.
AB  - The bacterial artificial chromosome (BAC) has become the most popular tool for
      cloning large DNA fragments. The inserts of most BAC clones average 100-200
      kilobases (kb) and molecular characterization of such large DNA fragments is a
      major challenge. Here we report a simple and expedient technique for physical
      mapping of BAC inserts. Individual BAC molecules were immobilized on glass slides
      coated with Poly-L-lysine. The intact circular BAC molecules were visualized by
      fluorescence in situ hybridization using BAC DNA as a probe. The 7.4 kb BAC
      vector was extended to approximately 2.44 kb per micrometer. Digitally measured
      linear distances can be transformed into kilobases of DNA using the extension of
      BAC vector as a standard calibration. We mapped DNA fragments as small as 2 kb
      directly on circular BAC molecules. A rice BAC clone containing both tandem and
      dispersed repeats was analyzed using this technique. The distribution and
      organization of the different repeats within the BAC insert were efficiently
      determined. The results showed that this technique will be especially valuable
      for characterizing BAC clones that contain complex repetitive DNA sequences.

PMID- 10205913
TI  - [94th annual meeting of the Japanese Society of Psychiatry and Neurology.
      Abstracts].

PMID- 10205914
TI  - [Effects of dehydroepiandrosterone on blood cells of the rat].
AB  - The effects of dehydroepiandrosterone (DHEA) on haemoglobin, hematocrit and white
      cell counts values were studied in male and female rats, castrated rats and
      pregnant rats. After 5 continuous days of DHEA administrated subcutaneously (80
      mg/kg/d; body w.) haemoglobin and hematocrit values were similar those values
      obtained before the treatment. White cell counts were reduced (40%) in female no
      castrated rats due to a significantly lymphopenia. The white cell counts were
      increased in castrated rats and with DHEA administration there were reduced to
      the initial values. Estradiol treatment had the same effect as DHEA on castrated
      rats. These data suggest that DHEA administrated to castrated or sexually active
      male and female rats affects the white cells without important effects on red
      blood cells.

PMID- 10205915
TI  - [Protein-energy malnutrition and hypobaric stress effects on ultrastructure of
      the heart muscle in rats].
AB  - A model that simulated nutritional and hypoxic stress is discussed. Wistar male
      adult rats were used in four groups: A1, A2, B1 and B2. A1 and A2 groups were fed
      with a diet whose composition was: 16% protein, 43% carbohydrate, and 6% lipids.
      Group B1 and B2 received the same type of diet but was restricted to 70% the
      amount consumed by groups A1 and A2. All groups were fed for 15 days. After these
      15 days, the half of both groups were introduced into an hypobaric chamber
      simulating an altitude of 3,500 m for two hours. Pieces of the rats hearts were
      used for biochemical and ultrastructural studies. In group B a dear decrease in
      the body and the heart weight was observed. Also a decrement of the heart
      proteins concentration was noticed. On the contrary the mitochondrial proteins
      increased. These biochemical changes correlate with the ultrastructural changes
      observed in the same group in which a decrease of the myofibrilles and abnormal
      configurations of the mitochondria were found. The undemourishment and the
      hypobaric stress produced an evident alteration in the ultrastructure of the
      heart.

PMID- 10205917
TI  - [Evaluation of the chemical characteristics and physical and rheological
      properties of the starch isolated from 2 amaranth species (Amaranthus cruentus
      and Amaranthus hypochondriacus)].
AB  - In this study the chemical composition, and the physical and rheological
      properties of starches isolated from seeds of three experimental varieties of
      Amaranthus cruentus and Amaranthus hypochondriacus, were evaluated. The starch
      content of amaranth grains was evaluated by two methods. The starch obtained
      showed a high purity with protein contents ranging from 0.90 to 0.93; the fat
      content was higher in A. cruentus starch than in the other two samples. The
      amylose content was different between the A. cruentus x A. cruentus sample
      (27.34%) and the other two starches (A. hypochondriacus; 12.47% and A. cruentus;
      12.61%). The rheological properties (amylographic and viscosity curves) of
      starches isolated from A. cruentus y A. hypochondriacus were similar.

PMID- 10205916
TI  - [Immunopathology of American tegumentary leishmaniasis].
AB  - The complex cell mediated immune response in parasitic diseases can be evaluated
      in different body compartments. In the present work we describe the results of
      studies of peripheral blood lymphocytes and the cutaneous lesions in the three
      clinical forms of tegumentary leishmaniasis. These clinical forms, that
      constitute a clinical, histological and immunological spectrum, are: localized
      cutaneous leishmaniasis (LCL), diffuse cutaneous (DCL9, and the intermediate
      forms that include mucous and verrocous leishmaniasis (MCL). The overall results
      suggest that the cytokine pattern of lymphocytes in the blood and lesions of LCL,
      the self-limiting form of the disease, is T-helper type 1. This leads to the cure
      of the lesions in these patients, either spontaneously or after appropriate
      therapy. The disseminated disease in DCL patients is resistant to chemotherapy,
      and is characterized by a Th2 cytokine pattern, with a an absence of IL-2 AND ifn
      gamma production when the lymphocytes are specifically stimulated by leishmanial
      antigen. This is probably why these patients are unable to control the infection,
      and allows the cutaneous dissemination of the parasite. The intermediate MCL form
      is characterized by destructive lesions of the oral and nasopahryngeal mucosas,
      with a tendency to the chronicity of the infection. The cytokine pattern of MCL
      patients is a mixture of Type 1 and Type 2 responses. This may be responsible for
      the progression of the disease in these patients, as it is possible that when
      both types of cytokines are produced, the Type 2 responses can predominate over
      the Type 1 and the disease is maintained in a chronic, although activated, state.
      The examination of the cutaneous lesions demonstrated that the epidermis in the
      DCL lesions is deficient in ICAM-1 accessory signals and MHC-II expression by
      keratinocytes, and presents a variable number of Langerhans cells. In MCL
      lesions, the expression of ICAM-1 and MHC-II is elevated, and Langerhans cells
      are absent in the damaged epithelium. The epidermis of LCL lesions show ICAM-1 in
      patches and MHC uniformly expressed by keratinocytes. DCL lesions are
      characterized by low CD4/CD8 and memory/naive T cell ratios, low numbers of T
      gamma delta cells, and an apparent defect in the expression of LFA-1 directional
      receptors. The cytokine patterns are Th1 and Th2, with the latter predominating.
      MCL granulomas manifest high CD4/CD8 and memory/naive Tcel ratios, low numbers of
      T gamma delta, a high coefficients of cellular adhesion, with a mixed Th1/Th2
      cytokine pattern. LCL granulomas are characterized by a normal CD4/CD8 ratio, a
      high memory/naive cell ratio, numerous groups of T gamma delta, a high expression
      of directional receptors, and Th1/Th0 cytokine patterns. We discuss the results
      in the context of the immunological effects, both in immunotherapy and
      immunoprophylasis, of the combined vaccine of BCG plus promastigotes of
      Leishmania. In immunotherapy we demonstrate that the combined vaccine simulates a
      Th1 response in LCL patients. As an immunoprophylactic vaccine in healthy
      individuals from an endemic area of leishmaniasis, it stimulates a Th1 response
      (positivity in the Montenegro cutaneous reactions, proliferative responses in
      vitro and production of IFN-gamma), with a low specific antibody response. This
      demonstrates that the combined vaccine is potentially useful both in the
      treatment of LCL patients, as well as being potentially protective applied as
      immunoprophylaxis in the control of leishmaniasis.

PMID- 10205918
TI  - [Comparative evaluation of triamcinolone in coccidiosis control in fattening
      chickens].
AB  - The effectiveness of Triancinolone as a protector against coccidiosis in broilers
      was tested in a random design experiment. Cobb x Cobb one-day old chicken were
      assigned to the treatments: T1: no medication-no inoculation; T2: no medication
      inoculation; T3: Triancinolone-inoculation; T4: Sodic Monensin-inoculation; and
      T5: Sodic Salinomycin-inoculation. The inoculation was accomplished with 10,000
      oocysts of Eimeria tenella and 40,000 of intestinal Eimerias. The results of the
      intestinal damage degree showed that T3 (60.6%) and T4 (63.6%) were better to
      control coccidias in relation to T5 (96.9%) and T2 (100%). The oocysts number in
      feces (number/g) showed the best effectiveness for T3 (4,300) comparing with T4
      (126,900), T5 (98,100), and T2 (382,000). These results emphasize the effective
      action mechanism of Triancinolone to interfere with the biological cycle of
      coccidias. The feed conversion was better (P < 0.05) in the groups that received
      the drugs (T3, T4, and T5) comparing with T2. This fact showed the adverse effect
      that coccidiosis cause on the broiler performance behavior. Triancinolone showed
      the best action effectiveness on the control of coccidiosis.

PMID- 10205919
TI  - [Evaluation of a linear TEOAE protocol in hearing screening of neonates:
      feasibility study].
AB  - The audiological screening of newborns based on recording TEOAEs--the expression
      of anatomical-functional integrity of the cochlea--has unanimously gained
      importance. The prevalence of severe of genetic or congenital hearing loss in the
      healthy infant population and in the population at risk for audiological
      disorders, as well as the consequent psycholinguist and socialization problems
      such children have to deal with, have led the authors to set up a preliminary
      protocol for the audiological screening of neonates. The purpose of this protocol
      is to improve the feasibility of applying such a program. To this purpose, the
      preliminary protocol called for the recording of the TEOAE in both non linear
      (NL) and linear (L) modes. Examination was performed in 347 newborns (30% of all
      the children born during 1997) the second day of life and during spontaneous
      sleep. The ILO 92 was used for the screening. The results obtained with the two
      methods were statistically compared using the 9 parameters considered response
      indicators. Using the linear method of a function-window and improving the signal
      to-noise ratio, the study showed a significant difference in the quality of the
      TEOAE using the linear method as compared with the non linear method, although
      this did not modify response reliability. This lead to the definition, through
      free distribution statistical analysis, of broader than normal criteria by which
      to evaluate the responses evoked with the L method. All this is aimed at
      increasing system specificity and reducing the number of false positives which
      feeds family anxiety.

PMID- 10205920
TI  - [Sudden idiopathic hearing loss. Case reports in the course of ten years].
AB  - The authors present a retrospective case study of 132 subjects with sudden-onset
      hearing loss who had been observed during the course of 10 years. The results
      were compared with those available in the literature. These patients were divided
      into two subgroups based on age: over or under 40. The hearing loss was divided
      into 4 subgroups according to audiogram morphology. Then the presence, and
      entity, of any recovery in hearing was evaluated. There was no preference for sex
      while the greatest incidence was found in the VI and VII decade of life. The
      audiohistograms obtained when the patients were admitted to the hospital and 2
      months later indicated an improvement in the hearing threshold localized above
      all in the medium-low frequencies. This confirms a better evolution in those
      forms localized in the apex of the cochlea. The threshold of 60 dB HL is the
      dividing line between a totally favorable prognosis and a partially or totally
      unfavorable prognosis. This indirectly confirms that the intensity of the initial
      hearing damage is an important prognostic factor. From the morphological point of
      view the forms with the best evolution appear to be those with a flat or rising
      morphology. The forms with descending morphology do not present a favorable
      evolution although those with a threshold around 8000 Hz are worse than those
      with a threshold of 4000 Hz. As regards age no significant differences were found
      in the evolution of hearing loss between subjects under and over 40. In
      conclusion, the essential characteristics of sudden-onset hearing loss are as yet
      poorly defined. There are so many variables affecting the onset and evolution of
      hearing loss that it proves impossible to perform any statistically valid
      analysis which includes them all. To date the elements able to provide some
      degree of prognostic prediction are the audiogram morphology and the entity of
      the initial hearing loss.

PMID- 10205921
TI  - [Perforations of nasal septum: surgical considerations].
AB  - Perforations of the nasal septum vex both patients and physicians. A variety of
      methods have been devised to close septal perforations although none has gained
      universal acceptance. The following report presents a new approach for closing
      septal perforations using a modification of the Fairbanks technique. The "open"
      approach is performed as it provides easier access. A supporting graft is only
      used in the temporalis fascia, not in the cranial periosteum. Furthermore, the
      graft is sutured only on one side of the septum. Forty patients were treated with
      this technique and good results were obtained with small and mid-sized
      perforations (respectively 80% and 83%). In cases of large perforations the
      results were good enough (37.5%) to warrant recommendation of this technique.

PMID- 10205923
TI  - [Clinical significance of "ANCA" in the diagnosis of Wegener's granulomatosis: 8
      years of experience].
AB  - In its early stages Wegener's Granulomatosis (WG) commonly presents symptoms in
      E.N.T. sites. However, these symptoms are not specific and vary greatly so that
      alone they rarely lead to a correct diagnosis. Anti-neutrophil cytoplasmic
      autoantibodies (ANCA) have recently been found in patients with WG. The presence
      of such autoantibodies is now considered a specific test for this disorder. Over
      the last 8 years, 11 patients with WG having E.N.T. involvement were observed.
      All were tested for the presence of ANCA and such antibodies were found in 10 out
      of 11 patients. Biopsy showed the histopathological characteristics of WG--i.e.
      granulomatous necrotizing vasculitis--in five cases (in one patient biopsy was
      carried out surgically in the lung). Subglottic localization was surprisingly
      common in these patients, being seen nearly as frequently as the sinonasal
      localization (generally the most common manifestation of WG in the E.N.T.
      district). Early identification of the WG subglottic stenosis made it possible to
      administer appropriate medical therapy, thus limiting the number of surgical
      procedures. Only one patient was temporarily tracheostomized. None underwent
      laryngo-tracheoplasty. A major clinical problem in WG is to keep the interval
      between onset and definitive diagnosis as short as possible. At the outset, WG
      nearly always displays symptoms and signs in E.N.T. sites. Unfortunately,
      however, the diagnosis is nearly always made when pulmonary, or even worse renal,
      localizations appear. This considerably worsens the quoad vitam and quoad
      valetudinem prognosis. The authors' experience leads them to conclude that Anti
      neutrophil cytoplasmic autoantibodies, in their C-ANCA pattern, represent a
      useful tool for prompt diagnosis of Wegener Granulomatosis, particularly in
      limited or atypical forms.

PMID- 10205922
TI  - [Effect of sulfur salt-bromine-iodine thermal waters on albumin and IgA
      concentrations in nasal secretions].
AB  - In chronic rhinopharyngotubaric phlogoses, the key pathogenic element sustaining
      phlogosis is a persistent modification of the biological, rheological features of
      the nasal mucus. For centuries sulphurous thermal waters have proved effective in
      clinically curing such phlogoses. In order to evaluate the effect of such
      sulphurous-salty-bromic-iodic thermal waters a randomized, double blind study was
      undertaken on a sampling of 50 patients. The effect such waters have on secretory
      IgA (sIgA) and albumin in the nasal secretions was tested against a placebo made
      of distilled water. Using the method of radial immunodiffusion, the response in
      the IgAs (mg/l) and albumin (mg/dl) concentrations in the nasal secretions was
      measured for 25 patients treated with the thermal waters and 25 patients treated
      with distilled water. The average concentrations were statistically compared
      using the Student t-test for paired samples. A significant increase (p < 0.0001)
      was seen in the mean IgAs concentration in the patients treated with the thermal
      waters. On the other hand, there was a weak, not statistically significant
      increase in the same data mean for the group treated with distilled water. The
      average increase in the albumin concentration in the nasal secretions proved
      significant in both cases although the significance was much more marked in the
      group treated with the thermal waters (p = 0.001) vs. the placebo group (p =
      0.039).

PMID- 10205924
TI  - [Reconstructive strategies in head and neck cancer: case history review from 1992
      to 1997 (154 cases)].
AB  - Technological progress in reconstructive surgery, in particular the use of
      pedunculated or free flaps, has given new impetus to head and neck dissection.
      This stems from the fact that such techniques provide greater oncological
      radicality, reduce the number of severe post-operative complications and give
      better quality of life. The present study examines 154 patients suffering from
      upper aero-digestive tract neoplasms (131 males and 23 females; age range 23-82
      years) who had undergone radical surgery. Reconstruction was performed with flaps
      in 154 cases: 119 pedunculated flaps (102 large myocutaneous pectoral and 17
      temporal muscle flaps) and 35 free flaps (18 radial osteofasciocutaneous, 13
      radial fasciocutaneous and 4 omentum flaps). Analysis of the individual districts
      showed that the flap of choice was the temporal muscle flap when surgery involved
      the soft parts of the orbital-maxilly-zigomatic area and the rhinopharynx. This
      is because it is highly moldable and reliable. In surgery of the oral cavity and
      oropharynx the grand pectoral flap is most frequently used as it provides enough
      tissue for the reconstruction, adequately protects the vascular-nerve axis in the
      neck and it is quick and easy. However, the functional results are not the best
      and there is some alteration in the initial phases of deglutition. To reduce
      these problems, the authors encourage the use of free flaps which provide good
      results from both the functional and esthetic points of view. They are, however,
      more difficult to perform and this leads the authors to conclude that they should
      only be selected for certain patients (long life expectancy, female, young,
      etc.). In the center where the authors work the flap of choice is the radial
      fasciocutaneous or osteofasciocutaneous flap. In surgery of the hypopharynx and
      larynx reconstruction is normally performed with a grand pectoral myocutaneous
      flap, sculpted as needed for the individual case. In this region, reconstruction
      proves functionally satisfactory even when there is a minimum of residual mucosa.
      Finally, for reconstructive surgery of the apex, the omentum free flap was used
      as it is malleable and can be used to reconstruct broad areas of dissection. The
      esthetic and functional results, the low incidence of complications and the
      greater quality of life suggest that this type of flap be extended to the surgery
      of locally advanced tumors in combination with an accurate, valid reconstructive
      solution.

PMID- 10205925
TI  - [Otogenic cerebral abscess: description of 3 cases, clinical and therapeutic
      considerations].
AB  - The authors use the 3 cases of otogenous cerebral abscess which came under
      observation as starting point for a discussion of the main etiopathogenetic,
      microbiological, clinical-diagnostic and therapeutic aspects of this disorder.
      After a brief presentation of the data regarding incidence, preferential
      localization and age of onset, they discuss the means for intracranial spread of
      infection and the related symptoms. As regards diagnosis, the authors assert that
      clinical examination and imaging techniques--CT and especially MRI--enable one to
      determine the dimension and site of the abscess cavity, differentiating it from
      other intracranial lesions and to monitor clinical evolution and response to
      therapy. After mentioning the principle bacteria involved in infection, they deal
      with the various means of treatment. The authors favor surgical removal of the
      auricular phlogistic focus and medical treatment of the intracranial abscess.
      They resort to neurosurgery only in those cases which do not respond to drug
      treatment or when the size and particular location of the abscess threaten the
      patient's life. In conclusion, the authors underline the problems seen today in
      diagnosis and therapy, comparing the quoad vitam and quoad valetudinem prognosis
      for the affected patients.

PMID- 10205927
TI  - [Progressive sensorineural hearing loss: definition, classification, main
      etiological factors].

PMID- 10205926
TI  - [Metastasis in the inner auditory canal].
AB  - Metastasis in the inner auditory canal (IAC), or more precisely in the
      pontocerebellar angle (PCA) is extremely rare. Indeed acoustic neurinoma (AN),
      meningioma and other types of benign neoformations, in decreasing order, account
      for nearly all expansive pathologies in this anatomical region. The present paper
      reports a clinical case of a patient with the sudden onset of an hearing loss in
      the right ear. This hearing loss was promptly followed by paralysis of the
      homolateral facial nerve. The function of both cranial nerves worsened
      progressively and rapidly. Cerebral radiology, performed with MRI and the
      administration of gadolinium, showed a AN-compatible neoformation fundamentally
      affecting the IAC. However, histological tests performed after surgery indicated
      an adenocarcinoma. Post-operative instrumental tests identified the primary
      neoplasm in the lower lobe of the right lung. The purpose of this work was to
      highlight, in view of the literature on the topic, the main clinical aspects to
      consider when a malignant expansion is suspected in the PCA. Naturally there is
      greater basis for such suspicion when a primary malignant neoplasm has previously
      been diagnosed. Generally AN progresses quite gradually, in line with an
      extremely slow growth rate. Therefore it is normally seen in a progressive
      worsening of hearing, tinnitus and equilibrium disorders. Appearance of a facial
      nerve palsy is strictly limited to relatively large neoplasms and is encountered
      at a later stage. This is why a rapid progression of hearing damage accompanied,
      or promptly followed, by complete facial nerve paralysis must alert one to the
      possibility of a PCA malignancy. Imaging does not permit easy pre-operative
      diagnosis since the radiological signs and morphologies are often quite similar
      to those produced by AN. Therefore, post-operative histological examination can
      hold some surprises.

PMID- 10205928
TI  - [Progressive sensorineural hearing loss in childhood].
AB  - Prevalence of progressive sensorineural hearing loss in childhood seems to be
      extremely variable, as percentages reported range from 4 to 30%. Differences in
      the criteria employed for identifying the deterioration, in the groups of
      patients, and the age range, could explain this wide range of reported figures.
      The etiology of the progressive sensorineural hearing loss in infants can be
      hereditary or acquired. Hereditary causes are divided into syndromic and non
      syndromic, whereas the acquired causes include congenital or acquired infection
      (syphilis, cytomegalovirus, rubella virus and toxoplasma infections, bacterial
      meningitis and acquired viral infections) and congenital inner ear anomalies
      (Mondini's dysplasia, large vestibular aqueduct, large cochlear aqueduct). Other
      acquired causes such as disorders of the metabolism, chronic use of ototoxic
      drugs, autoimmune diseases, perilymphatic fistula and head or acoustic trauma are
      less common. The age of onset of deterioration shows a great variability because
      even the congenital hearing losses may occur late after birth. The progressive
      evolution seems to be binaural in most patients, but more commonly it presents
      interaural differences, and when the hearing deficit is initially asymmetrical
      the deterioration is usually greater in the ear which appeared least affected in
      the first audiogram. Furthermore, at the different frequencies, there is a
      tendency to a greater deterioration at the frequencies initially least affected,
      but some authors are not in agreement because they report a uniform pattern of
      progression in the range of 0.5 to 4 kHz with no modification of the audiometric
      shape in most of the examined patients.

PMID- 10205929
TI  - [Genetic type of progressive hearing loss].
AB  - In daily practice we tend to underestimate hereditary factors as a cause of
      hearing impairment especially in those cases of late-onset and progressive
      hearing loss. Genetic hearing impairment may be congenital but it also may
      develop at any decade throughout life or deteriorate as part of a pre-existing
      congenital or acquired hearing impairment. Over the past 5 years, hereditary
      diseases associated with hearing impairment have been mapped, and several of
      genes have already been identified. Identification of genes causing hereditary
      deafness, as with other genetic diseases, goes through two stages: first mapping,
      then cloning. One method used to identify candidate genes based on their function
      or pattern of tissue expression involves the construction of cDNA libraries from
      the target organ or tissue, in this case from the cochlea. Studies of the
      molecular genetics of the inner ear are hampered by its relative inaccessibility,
      by the limited numbers of cochlear and vestibular cells, and by our inability to
      maintain many of these cell types in long term culture. The construction and
      characterization of cochlear cDNA libraries from humans and other species provide
      an important resource for rapid identification of cochlear genes involved in
      normal hearing and in hearing disorders; cDNA libraries constructed at different
      stages of development, and subtracted from each other, could be instrumental in
      identifying genes important at each stage of development of the cochlea.
      Libraries made from different tissues within an organ (i.e. inner vs outer hair
      cells) could be compared to identify genes that are needed for the
      differentiation of the cells into specific types. In addition, these libraries
      have the potential to foster identification of other proteins unique to the
      cochlea and will contribute to the identification, characterization, and
      functional analysis of these cochlea-specific proteins. Another important
      application of cDNA libraries is for identifying hearing loss genes. Once the
      candidate gene for a given type of hearing loss is cloned and decoded, the
      structure of its protein product can be determined. This will provide insights
      into biochemical function of the gene product in normal cochlear tissue, and will
      show why the genetic mutation result in hearing loss. Pedegree analysis and
      audiometric morphology have been widely used to attempt a subcategorisation of
      many isolated or familial "genetic" cases. A debatable point is the influence of
      aging on a genetic hearing loss. Effects due to genetic factors are often not
      easily distinguishable from the age-related factors. According to our findings,
      the progression of hearing loss present in several different patterns, according
      to the different interactions between hereditary hearing loss and presbycousis.

PMID- 10205930
TI  - Congenital and acquired perilymph fistula: review of the literature.
AB  - Perilymph fistula is caused by an abnormal communication between the perilymph
      space and the middle ear. The etiology is either congenital or acquired. The
      congenital fistula can be associated or not with clinical symptoms or
      radiologically detectable abnormalities of the temporal bone. In patients
      presenting congenital fistula without symptoms or radiologically detectable
      abnormalities, little malformations of the middle ear may be detected during
      surgery. The acquired fistula can be caused by iatrogenic trauma, physical injury
      or erosion. As far as therapy is concerned, surgical treatment can be performed
      and the perilymph fistula thus represents one of the few causes of sensorineural
      hearing loss that can be treated surgically. However, the main challenge is the
      identification of those patients that need to undergo an exploratory tympanotomy,
      since there are no clinical-audiologic symptoms or radiographic indicators that
      can be considered pathognomonic of perilymph fistula. The aim of this review of
      the literature is to define the guidelines for preoperative diagnosis to indicate
      exploratory tympanotomy both in children and in adults. On the basis of our
      results, exploratory tympanotomy should be performed in patients with vertigo
      and/or progressive, sudden or fluctuating hearing loss in association with one or
      more than one of the following elements: a history of cranial trauma,
      radiographically detectable abnormalities of the inner ear, congenital
      malformations of the head, recurring meningitis, positive fistula test. The
      surgical treatment consists in placing a graft of temporalis fascia or tragal
      perichondrium and it usually results in a significant improvement of vestibular
      symptoms and sometimes of the hearing function as well.

PMID- 10205932
TI  - [Progressive sensorineural hearing loss: metabolic, hormonal and vascular
      etiology].
AB  - Metabolic, hormonal and vascular disorders are considered to cause hearing
      dysfunction such as progressive sensorineural hearing loss (PSNHL). The diseases
      most commonly associated with PSNHL are diabetes mellitus, congenital and
      acquired hypothyroidism, chronic renal failure, chronic labyrinthine ischemia
      determined by non-hematologic factors (tissue perfusion pressure, blood vessel
      diameter) or by hematologic factors (blood viscosity and/or rigidity of the red
      blood cells). In this study a review of data on the relationship between these
      clinical disorders and the presence and deterioration of the hearing function was
      carried out. PSNHL seems to be significantly associated with diabetes mellitus,
      in particular the mitochondrial type: a progressive deterioration of the hearing
      function is reported in 60% of the patients suffering from this type of disease
      with mitochondrial mutations. Regarding hypothyroid disorders, the data do not
      support a pathogenetic link between PSNHL and acquired hypothyroidism, whereas in
      subjects with congenital hypothyroidism both clinical and experimental results
      indicate a progressive damage of hearing function if the thyroid disorder is not
      treated early in life. Also, in patients with chronic renal failure the hearing
      thresholds seem to be significantly worse than in control subjects, particularly
      in patients undergoing dialysis, whereas the effect of kidney transplantation on
      auditory function is still not understood. Finally a relationship between PSNHL
      and chronic labyrinthine ischemia due to alterations of hematologic factors
      (increase of blood viscosity and/or increase of rigidity of the red blood cells)
      has been reported by several authors. However, data on high blood pressure and
      hyperlipoproteinemia as causes of deterioration of hearing acuity are
      controversial, and it is often difficult to understand whether the progressive
      hearing deficit is due only to these factors or also to the elderly age of
      patients.

PMID- 10205931
TI  - [Progressive sensorineural hearing loss: immunologic etiology].
AB  - An auto-immune progressive sensorineural hearing loss (PSNHL) can occur as one of
      the clinical features of systemic immune-mediated disorders, such as Cogan's
      syndrome, Behcet's disease, Wegener's granulomatosis, mixed cryoglobulinaemia,
      systemic sclerosis, systemic lupus erythematosus, giant cell arteritis,
      panarteritis nodosa, relapsing polychondritis, unclassified systemic
      vasculitides, etc, or as a distinct clinical entity, the so-called auto-immune
      inner ear disease. The clinical evolution of the hearing loss during the course
      of the systemic disease is extremely variable (slowly progressive versus rapidly
      progressive), while the auto-immune inner ear disease is usually characterized by
      a rapidly developing (weeks or months) progressive hearing loss. In both cases a
      timely clinical assessment and treatment can positively affect the prognosis of
      the hypoacusia. To date, no laboratory test will give a sure diagnosis of
      autoimmune hearing loss and only a good response to corticosteroid and/or
      cytostatic treatment can indirectly confirm this diagnosis. The laboratory tests
      that are usually performed can be divided into aspecific and specific tests, the
      latter evaluating the immune-mediated response to the specific inner ear antigen.
      Evaluation of the aspecific parameters sometimes shows high values of erythrocyte
      sedimentation rate and C-reactive protein, but often no alteration of the
      inflammation parameters is observed. However, the specific tests seem to achieve
      higher sensibility and sensitivity but to date they are not available in clinical
      practice. In this study we examined a group of 13 patients affected with
      bilateral idiopathic PSNHL who underwent Western Blot, which is a specific test
      for the inner ear antigen. A positive result was found in 53.8% of the cases; in
      particular, all 3 patients who had an improvement of hearing loss with
      corticosteroid treatment, and therefore were probably suffering from auto-immune
      progressive hearing loss, had a positive result to the Western Blot test.

PMID- 10205933
TI  - [Progressive sensorineural hearing loss from infectious agents].
AB  - The progressive sensorineural hearing loss due to infectious causes can involve
      different etiological agents like bacteria, viruses, protozoons or mycetes. These
      infectious agents can act in various ways: directly through a labyrinthitis that
      may destroy the neuroepithelium; through an ischaemic process secondary to a
      septic embolus; or through a thrombus. In some cases the damage can occur in a
      meningitis context, because of the passage of the germ in the inner through the
      nerves, the vases or the labyrinthine liquids. Bacterial meningitis is one of the
      causes of progressive sensorinueral hearing loss. Among bacteria, the
      Mycobacterium Tuberculosis has nowadays acquired a remarkable importance which is
      also due to its considerable diffusion, despite modern therapy, and to its
      association with HIV infection. Bacteria can also cause a labyrinthitis acting
      directly on the inner ear: among these, Treponemas Pallidum, a spirochaete which
      causes syphilis and Borrelia Burgdorferi, a spirochaete that causes Lyme Disease,
      must be mentioned. The viruses that are certainly involved in the etiology of
      progressive sensorineural hearing loss are Cytomegalovirus and Rubella virus. The
      virus usually causes a labyrinthitis after the viraemia, wich may be due to the
      passage of the virus from the blood to the endolymph, through the stria
      vascularis with the consequent infection of the sensorial cells of the organ of
      Corti. Less frequently the viral damage to the inner ear can occur after a
      vasculitis, a meningitis or an alteration of the cell-mediated immunity.
      Progressive sensorineural hearing loss can also occur because of some congenital
      viral infections such as those caused by Cytomegalovirus and Rubella virus. More
      recently even the Human Parvovirus B19 seems to have been involved. This virus
      seems to act through autoimmune and/or immunologic processes, like that causing
      sudden hearing loss in Lassa fever. Another viral infection which can nowadays
      more frequently be considered among the cause of progressive hearing loss is HIV.
      In the HIV infection the neurological toxic lesions due to the administered
      ototoxic drugs are added up to the damages caused by the opportunistic infectious
      agents (virus, bacterium, protozoon mycete). However, in these patients HIV
      itself could be the cause of the auditory and vestibular lesions. More rarely, a
      progressive hearing loss may be due to the action of a protozoon or mycete only.

PMID- 10205934
TI  - [Iatrogenic and non-iatrogenic factors as causes of progressive sensorineural
      hearing loss].
AB  - The aim of our study was to analyze factors such as noise, chemical drugs,
      industrial solvents and radiotherapy, which can cause cochlear lesions with
      progressive sensorineural hearing loss. Although an acute overstimulation by
      acoustic energy may induce an irreversible hearing loss, in most cases the noise
      induced deafness is related to the duration of the exposure and to the level of
      the acoustic stimulation. A permanent hearing deficit occurs when the acoustic
      level exceeds 85 dBs. Also several classes of drugs are described as having
      ototoxic potential: aminoglycoside antibiotics, loop diuretics, antimalarial
      drugs such as quinine, salicylates, some chemotherapeutic antineoplastic agents.
      Their potential ototoxic effect seems to be related not only to the molecule, but
      also to individual predisposition, dose and route of administration. Regarding
      the benzene derivatives, there is a relationship between their ototoxicity and
      factors such as duration of exposure and concentration in the local environment.
      Finally, radiotherapy to areas near the temporal bone may produce a degenerative
      insult to the vascular stria and the hair cell causing a progressive
      sensorineural hearing loss.

PMID- 10205935
TI  - [Progressive sensorineural hearing loss in cochlear otosclerosis].
AB  - Otosclerosis is a bone dysplasia limited to the otic capsule causing abnormal
      resorption and redeposition of bone. The existence of the entity "pure
      labyrinthine otosclerosis" or "cochlear otosclerosis" is not accepted by all
      authors; however, there is clinical and histologic evidence to support the
      existence of a progressive sensorineural hearing loss due to otospongiotic
      otosclerotic lesions of the labyrinthine capsule, although diagnosis of this
      condition may be difficult. The involvement of the inner ear is described as
      degenerative changes in the spiral ligament, stria vascularis, organ of Corti,
      and cochlear neurons. The most frequent audiometric configuration is a "bite
      type" curve, but flat or rising shapes can also be observed; speech
      discrimination appears unusually good for a pure sensorineural hearing loss and
      recruitment is frequently absent. A cochlear otosclerosis should be suspected
      when there is a family history of otosclerosis, the onset of the hearing loss
      occurs from the third to fifth decade, and worsening of the hearing loss is
      observed during periods of intense hormonal and endocrine activity, a positive
      Schwartze sign is present and bilateral sensorineural loss is associated with
      signs of unilateral stapedial ankylosis. A definitive diagnosis of cochlear
      otosclerosis can be made only with computed tomography, which allows a
      quantitative assessment of the involvement of the labyrinthine capsule by
      spongiotic or sclerotic areas. The factors to be considered are: otosclerotic
      foci 1 mm or more in diameter and a density different from that of the normal
      otic capsule, partially or completely erased contour of the capsule, double ring
      effect, bony neoformation in the labyrinthine spaces, and increased thickness of
      the cochlear capsule. The medical management of cochlear otosclerosis is based on
      sodium fluoride, in association with calcium and vitamin D; some authors have
      also proposed diphosphonates as inhibitor agents of bone resorption. Surgery may
      be useful only in those patients presenting a hearing loss so severe that the
      bone threshold cannot be evaluated and a gap between air and bone conduction
      cannot be excluded; in these cases stapes operations can improve hearing to a
      level that may be useful in hearing aid application.

PMID- 10205936
TI  - [Delayed endolymphatic hydrops].
AB  - Delayed Endolymphatic Hydrops (DEH) is a disease entity that must be
      distinguished from idiopathic endolymphatic hydrops (Meniere's disease).
      Idiopathic hydrops is characterized by the following symptoms: 1) vertigo often
      accompanied by nausea and vomiting; 2) tinnitus; 3) hearing loss, usually
      fluctuating; and 4) sensation of pressure or fullness in the affected ear.
      Idiopathic hydrops most commonly occurs in middle-aged patients, usually between
      30 and 50 years. It may involve one or both ears and usually exibits fluctuating
      hearing loss and episodic vertigo, although one symptom may precede the other by
      months or years. It is rare for Meniere's disease to present with a severe
      sensorineural hearing loss. Delayed Endolymphatic Hydrops was first described,
      under the name of "unilateral deafness with subsequent vertigo", by Wolfson and
      Lieberman and Nadol et al.; this was later confirmed by other authors. The
      disease is characterized by a profound sensorineural hearing loss in one ear,
      found to have been present in most cases from early childhood, due to an unknown
      cause, trauma or viral infections. After a prolonged period (usually many years)
      patients with DEH experience the onset of episodic vertigo from the deaf ear
      (Ipsilateral Delayed Endolymphatic Hydrops) or develop a fluctuating hearing loss
      and/or episodic vertigo in the opposite ear, previously with normal hearing
      (Controlateral Delayed Endolymphatic Hydrops). Vestibular symptoms are identical
      to those of Meniere's disease: in fact there is evidence that endolymphatic
      hydrops in the previously damaged ear or in the previously normal ear represents
      at least part of the labyrinthine pathology. Histopathology studies recently
      conducted on temporal bones of subjects affected with controlateral DEH show
      pathologic changes in the deaf ears similar to those found in viral
      labyrinthitis, whereas pathologic changes in the hearing ears resemble those
      known to occur in Meniere's disease. Medical treatment has not been found to be
      effective in patients with DEH, but it must be the first choice of treatment
      especially in controlateral forms of the disease. So far, surgical intervention
      has been demonstrated to give the best results; either conservative or more
      radical, depending on the type of DEH. Pharmacological labyrinthectomy with
      ototoxic drugs could be the therapy of choice in the future. In this paper we
      review the literature in order to summarize the clinical features and criteria
      for diagnosing DEH, we also report histopathologic findings and pathogenetic
      hypotheses formulated for this syndrome. Moreover, we discuss the best
      therapeutic approach for the ipsilateral and controlateral variants of DEH.

PMID- 10205937
TI  - [Progressive sensorineural hearing loss: neoplastic causes].
AB  - Acoustic neuromas represent about 90% of all space-occupying lesions of the
      cerebellopontine angle and account for approximately 6% of all intracranial
      tumors. Progressive unilateral sensorineural hearing loss is the most frequent
      initial symptom occurring in over 90% of patients. A sudden onset of hearing loss
      occurs in 5%, while 5% of cases present with normal hearing. The incidence of
      hearing loss does not seem to be related to tumor size. Accuracy of the tumor
      detection by gadolinium-enhanced magnetic resonance imaging has been reported as
      99-100% even for intracanalicular tumors. The ABR false negative rate for
      intracanalicular tumors has been reported to be as high as 9-11%. Rare lesions of
      the cerebellopontine angle include: meningiomas, epidermoids, arachnoid cysts,
      trigeminal nerve neuromas, facial nerve neuromas, neurinomas of lower cranial
      nerves, glomus tumors and metastases. Therefore, a high suspicion index and
      awareness of symptoms and an adequate audiologic and neuroradiologic work-up are
      the clues to early diagnosis and appropriate surgical treatment.

PMID- 10205938
TI  - [Presbycusis].
AB  - Presbycousis represents a poorly defined clinical entity despite a number of
      investigations that have been carried out. After a careful review of present
      knowledge, the authors state that this clinical entity may be regarded as a
      multifactorial syndrome, due to extrinsic as well as inherited noxious factors.

PMID- 10205939
TI  - [MRI in progressive sensorineural hearing loss].
AB  - Magnetic resonance contrast imaging using gadolinium-DTPA and performing new high
      resolution sequences (Fast Spin-Echo, Spoiled Gradient-Echo) or angiographic
      sequences (Magnetic Resonance Angiography) allows an excellent visualization of
      the inner ear and the cerebellopontine angle to be obtained. Furthermore, using
      sequences obtained with the "steady-state" technique (Gradient Recalled At Steady
      State-GRASS, Constructive Interference at Steady-State-CISS), a good analysis of
      the structures of the membranous labyrinth can be achieved. Based on these
      diagnostic techniques, we have studied the morphological features of the
      membranous labyrinth in patients with progressive sensorineural hearing loss due
      to inner ear malformations, labyrinthitis, neuritis of VII and VIII cranial
      nerves, degenerative entities such as otosclerosis and Meniere's disease,
      neoplasms of the cerebellopontine angle, of the inner ear and of the middle ear
      (glomus tumours, acoustic neuromas, meningiomas, epidermoid tumours, arachnoid
      cysts and malignant neoplasms).

PMID- 10205940
TI  - [Diagnostic and therapeutic approach to progressive sensorineural hearing loss].
AB  - Progressive sensorineural hearing loss (PSNHL) is an important clinical entity
      that can develop rapidly and evolve to deafness. The causes of PSNHL can be
      divided into hereditary, developmental, infectious, autoimmune, metabolic,
      vascular, neoplastic, toxic and degenerative, even if the origin of the hearing
      impairment often remains unknown and a diagnosis of idiopathic PSNHL is made. In
      order to establish the etiology of the hypoacusia or to rule out any known
      etiology of PSNHL and to diagnose an idiopathic form, a detailed family,
      physiological and medical history has to be obtained, including history of
      pregnancies. A careful audiological and otoneurological evaluation should also be
      carried out, followed by laboratory tests. Furthermore, a complete
      otoneurological evaluation is required, with puretone audiometry, speech
      audiometry, impedance audiometry and study of the stapedial reflex, brainstem
      auditory evoked potentials and vestibular examination. Finally, patients with
      PSNHL must undergo neuroradiological examination (computerized tomography of
      petrosal bone, cerebral magnetic resonance and inner ear magnetic resonance);
      ophthalmological, rheumatological and neuropsychiatric (in childhood) advices
      should be sought, while other advices may be required on the basis of a
      particular clinical suspicion. When the etiology is established, therapy must be
      based on specific treatment for the cause of the hearing deficit; for example,
      hormonal therapy in alterations of thyroid function, antibiotic treatment in
      bacterial infections, calcium-antagonist and antiaggregant drugs in the vascular
      forms, corticosteroids or cyclophosphamide or other immunosuppressive drugs in
      PSNHL associated with systemic autoimmune diseases. In idiopathic hearing loss,
      treatment must be started in the absence of important contraindications. The
      therapeutic protocol that we use in such cases is the following:
      methylprednisolone boluses, 500 mg/day for three consecutive days, and
      subsequently oral treatment gradually tapering off in association with a cycle of
      hyperbaric therapy. Patients showing clinical and historical indications are also
      treated with intravenous glicerolo, calciparina and/or antiaggregant and calcium
      antagonist drugs.

PMID- 10205941
TI  - Changing supply and earning patterns of the mental health workforce.
AB  - The authors examine recent trends in the supply and earnings of various mental
      health providers from 1989 to 1995. The makeup of the mental health workforce is
      fundamentally different now than a decade ago. The number and earnings of
      psychiatrists have been relatively flat. The number of psychologists increased by
      24%, with their earnings rising rapidly in the 1980s, and remaining level since
      1990. The number of clinically trained social workers increased by 87% over the
      same period, and the number of advanced practice nurses certified in mental
      health specialties almost doubled, with the earnings of these master's-level
      providers increasing steadily over the period described. These trends are
      discussed in the context of major changes in the financing and delivery of mental
      health care.

PMID- 10205942
TI  - Racial/ethnic disparities in admissions to public and private psychiatric
      inpatient settings: the effect of managed care.
AB  - This study investigates the effect of managed care on access patterns among
      people of color who are severely and persistently mentally ill. The distribution
      of admissions to public and private psychiatric hospitals was compared for
      African-American, Asian, Latino, and white case managed clients of the
      Massachusetts Department of Mental Health before and after implementation of
      Medicaid managed mental health care in October 1997. Managed care appears to have
      increased access to private services across all racial and ethnic groups,
      although admissions of non-white patients were still more likely to take place in
      publicly operated settings. These data suggest that equalizing access to
      putatively better inpatient treatment settings may be an externality of managed
      care.

PMID- 10205943
TI  - What mental health teams want in their leaders.
AB  - The authors present the findings of the first phase of a 3-year study developing
      a skills training curriculum for mental health team leaders. A factor model
      empirically generated from clinical team members was compared to Bass' (1990)
      Multifactor Model of Leadership. Members of mental health teams generated
      individual responses to questions about effective leaders. Results from this
      survey were subsequently administered to a sample of mental health team members.
      Analysis of these data yielded six factors: Autocratic Leadership, Clear Roles
      and Goals, Reluctant Leadership, Vision, Diversity Issues, and Supervision.
      Additional analyses suggest Bass' Multifactor Model offers a useful paradigm for
      developing a curriculum specific to the needs of mental health team leaders.

PMID- 10205944
TI  - The impact of case management on utilization of community support services in a
      rural state.
AB  - The authors report on a study testing the hypothesis that persons with serious
      mental illness (SMI) would report more utilization of community support services
      if they had a case manager. Individuals with SMI were asked to complete a survey
      reporting their use of 10 community support services and case management. Having
      a case manager was not associated with increased utilization of any support
      service or case management by persons with serious mental illness in this rural
      state.

PMID- 10205945
TI  - The "modest needs" homeless family.

PMID- 10205946
TI  - The impact of managed care on psychiatry.
AB  - It is estimated that 50% of all practicing psychiatrists have at least one
      contract with a managed care organization (AMA, 1994). As the field of psychiatry
      increasingly adopts the tools of managed care, it is important for researchers to
      clarify the extent to which managed care affects the practice of psychiatry, and
      how the changing practice climate in turn affects patients seeking mental health
      care. A diverse array of managed care techniques have been introduced into the
      profession of psychiatry in an effort to alter treatment patterns. One commonly
      used tool, utilization review, can alter treatment patterns by restricting access
      to treatment alternatives and providing incentives to practitioners to meet
      managed care goals. Other managed care tools are the determination of "medical
      necessity" and the use of triage and treatment guidelines among insured enrollees
      requesting services. These guidelines serve as selection criteria to help
      determine not only which members of the insured population receive treatment for
      mental health care, but also to determine the allocation of enrollees to staff
      members and to prescribe the starting point for the types of services received.
      Managed care psychiatrists may find changes not only in their client populations
      and treatment alternatives, but in many other aspects of their practice. Some
      psychiatrists working in managed care have become increasingly involved in
      treatment teams. Other psychiatrists contracting with MCOs are reserved for
      medication management, consultation, or administration in carved-out mental
      health departments or agencies. Little is known about the extent to which managed
      care restrictions affect psychiatrists' patient care roles, collaborative
      relationships with other mental health professionals, and the degree to which
      psychiatrists are involved in administration of managed mental health care
      benefits. The era of managed care has constrained the clinical decision making of
      psychiatrists whose magnitude and impact on job satisfaction and labor market
      responses are unknown. Surveys of general physicians in MCOs have provided a
      framework for understanding some of the difficulties and opportunities faced by
      managed care psychiatrists, but have failed to shed much light on many aspects of
      medical practice specific to the provision of mental health care within the
      boundaries of managed care. Future research in this area would help fill this
      gap, and assist in shaping the roles of psychiatrists in managed mental health
      care organizations.

PMID- 10205947
TI  - Mike Grace interviews Fred Smales, Dean of the Faculty of Dentistry, University
      of Hong Kong.

PMID- 10205948
TI  - Safe sedation.

PMID- 10205949
TI  - Acupuncture and dental pain.

PMID- 10205950
TI  - Lack of training for nurses in oral care.

PMID- 10205951
TI  - A review of patient satisfaction: 1. Concepts of satisfaction.
AB  - Against a background of growing consumerism, satisfying patients has become a key
      task for all healthcare providers. This paper reviews current conceptual models
      of consumer satisfaction, including the one most dominant in the marketing
      literature--disconfirmation theory.

PMID- 10205952
TI  - A review of patient satisfaction: 2. Dental patient satisfaction: an appraisal of
      recent literature.
AB  - This paper examines the way patient satisfaction is perceived in the dental
      literature. The majority of studies carried out since the early 1980s concentrate
      on patient perceptions of various service quality attributes and the role that
      sociodemographic variables play in determining satisfaction. Recent work
      concerning attribution theory suggests that two concepts, duty and culpability,
      may be central to explaining this process.

PMID- 10205953
TI  - Geographic distribution of private dentists in Hong Kong in 1989 and 1998.
AB  - More than 80% of the dentists in Hong Kong are in private practice and third
      party payment schemes are uncommon. Thus, most dentists have to work according to
      the rules of a free market and have to respond to the demands of the population.
      Using official data, it was found that the geographic distribution of private
      dentists was highly uneven. In 1989, the dentist to population ratio in the
      commercial districts was below 1:2,500 while in the new towns the ratio was
      larger than 1:20,000. There has been an improvement in the availability of
      dentists in the under-served areas during the past 10 years although there are
      still a considerable number of dentists practising in the areas on both sides of
      the Victoria Harbour.

PMID- 10205955
TI  - Management of pseudo Class III malocclusion in southern Chinese children.
AB  - AIM: To illustrate a simple effective method for early treatment of pseudo Class
      III in the mixed dentition and to highlight the advantages of early treatment by
      showing a 4-year follow-up of the treatment effects. SUBJECTS: Twenty-one
      consecutive southern Chinese patients with a mean age of 9.6 years were included
      in the early treated group with pseudo Class III malocclusion. METHODS: Lateral
      cephalometric films taken at the beginning and at the end of treatment were
      analysed. The arithmetic mean and standard deviation (SD) were calculated for
      each cephalometric variable and paired t-tests were performed to assess the
      statistical significance of the treatment effects. RESULTS: Anterior crossbites
      and mandibular displacements were eliminated after the treatment. The angulation
      of the upper incisors to the maxillary plane showed an increase by a mean of 9.5
      degrees (P < 0.001), while the angulation of the lower incisors to the mandibular
      plane showed a decrease by a mean of 4.9 degrees (P < 0.001). CONCLUSION: In
      pseudo Class III malocclusion, proclination of upper incisors and/or
      retroclination of lower incisors with simple fixed appliances contribute to the
      correction of anterior crossbite and the elimination of mandibular displacement.
      Proclination of upper incisors, use of Leeway space and arch width increase
      provide space required for the eruption of the premolars and canines.

PMID- 10205954
TI  - Chemomechanical removal of dental caries in deciduous teeth: further studies in
      vitro.
AB  - OBJECTIVE: To further investigate the efficacy of N-monochloro-DL-2-aminobutyrate
      (NMAB) and NMAB containing 2 M urea (NMAB-urea) as chemomechanical caries removal
      reagents in deciduous teeth using standardised lesions and limited applicator
      pressure. DESIGN: In vitro. METHOD: Carious dentine was removed from standardised
      lesions in deciduous teeth using NMAB, NMAB-urea or isotonic saline (control); 50
      lesions were studied with each reagent. The surface of the dentine remaining in
      cavities where complete caries removal was achieved was examined by light and
      scanning electron microscopy. MAIN RESULTS: NMAB-urea (but not NMAB) gave
      significantly improved caries removal compared with saline. The dentine surfaces
      remaining after complete caries removal were irregular and approximately one
      third were bacterially contaminated. CONCLUSIONS: The improved efficacy of NMAB
      by the addition of urea has been confirmed. Toxicity studies are still necessary
      prior to clinical use of this reagent.

PMID- 10205956
TI  - Cephalometric morphology of Chinese with Class II division 1 malocclusion.
AB  - AIM: To investigate the craniofacial pattern of southern Chinese children with
      Class II Division 1 malocclusion and to compare with Chinese population norms and
      Caucasians with Class II Division 1 malocclusions. MATERIALS: Lateral
      cephalograms obtained from 105 Chinese subjects with Class II Division 1
      malocclusion. RESULTS: There were no significant sex differences and subsequently
      the data were pooled. Except for the maxillary plane angle and the angle of the
      lower incisor relative to the mandibular plane, all of the selected dental
      skeletal angular measurements showed significant differences between Chinese with
      Class II Division 1 malocclusion and Chinese norms. CONCLUSION: Compared with
      Caucasians, Chinese with Class II Division 1 malocclusion have more prognathic
      maxillas, less retrusive mandibles, flatter chins, steeper mandibular plane
      angles and more proclined maxillary incisors.

PMID- 10205957
TI  - Embedded problem-based learning of a clinical subject.
AB  - A problem-based learning approach was used for the 'teaching' of a fourth-year
      bridge course in an attempt to improve student learning and academic performance
      in the clinical environment. The introduction of problem-based learning requires
      careful planning as to the desired educational objectives and design.

PMID- 10205958
TI  - CONSORT. Consolidated Standards of Reporting Trials.

PMID- 10205959
TI  - Human nature and clinical freedom, barriers to evidence-based practice?
AB  - The perceived threat to clinical freedom offered by evidence-based practice is
      neither logical nor surprising. Resistance to change and to authority is part of
      human nature. When we make decisions based upon good quality information we are
      inconsistent and biased. Human nature offers many challenges to evidence-based
      practice. Can we do a better job of promoting evidence-based practice? And even
      if we find and use the evidence, will we make consistent unbiased decisions?

PMID- 10205960
TI  - Intra-venous sedation.

PMID- 10205961
TI  - Sedation service.

PMID- 10205962
TI  - Standards and dental suppliers.

PMID- 10205963
TI  - Post-operative review.

PMID- 10205964
TI  - Warm warning.

PMID- 10205965
TI  - Statutory registration for dental nurses.

PMID- 10205966
TI  - Need for a school dental service.

PMID- 10205967
TI  - The role of the dental nurse in general practice.
AB  - Dental nurses have reported dissatisfaction with their work which is associated
      with feelings of lack of control and being undervalued. This paper examines some
      of the possible reasons behind job dissatisfaction with illustrations from a
      pilot study conducted in general dental practice.

PMID- 10205968
TI  - Occlusion and splint therapy.
AB  - Control of occlusal contacts is important to the success of restorative
      dentistry. Tooth surface loss can contribute to a loss of stability in the
      occlusion. An occlusal splint is often part of pre-restorative management and can
      also have a valuable role in protecting both teeth and restorations from
      excessive loads and further wear.

PMID- 10205969
TI  - Allergic reactions to lignocaine.
AB  - True allergic reactions to local analgesics are extremely rare. This case report
      illustrates the procedures adopted to manage a patient with a history of
      suspected allergy. A young woman was found to have a true type I hypersensitivity
      to lignocaine. Another routinely used local analgesic agent, prilocaine, was
      tested by the same methods and found to give no allergic response. Dental
      treatment was successfully completed using the latter and the patient advised to
      wear a medical alert bracelet.

PMID- 10205970
TI  - Medical emergencies in general dental practice in Great Britain. Part 3:
      Perceptions of training and competence of GDPs in their management.
AB  - OBJECTIVES: To ascertain the training received in management of medical
      emergencies recalled by general dental practitioners (GDPs), as undergraduates
      and since graduation, to examine how well prepared they felt to manage such
      events and how their readiness might be improved. DESIGN: Postal questionnaire
      survey of a random sample of GDPs in Great Britain. SUBJECTS: 1500 GDPs, 1000 in
      England & Wales and 500 in Scotland. RESULTS: There was a 74% response. Among
      respondents, 75% had received training as undergraduates in the management of
      medical emergencies, 95% had subsequently received training. The proportion
      considering themselves 'well' or 'fairly well' prepared to manage emergencies
      rose from 30% at graduation to 80% currently. The 20% who felt themselves 'not
      very well' or 'not at all' prepared were less likely to possess the drugs and
      equipment to manage an emergency. Nevertheless, a need for further training was
      expressed by 96%: only 3% felt no need. CONCLUSIONS: Virtually all GDPs (99.2%),
      had received training in the management of medical emergencies at some time,
      principally since graduation. The 20% who feel inadequately prepared are less
      likely to possess the necessary drugs and equipment. There is a perceived need
      for further training among the majority of respondents.

PMID- 10205971
TI  - Dental caries, social deprivation and enhanced capitation payments for children.
AB  - OBJECTIVE: Investigate the appropriateness of the under fives' enhanced
      capitation scheme. DESIGN: Calculation of mean caries indices for socially
      deprived wards (Jarman score 2.5 or greater) and less socially deprived wards
      (Jarman score below 2.5) in Sheffield using dental epidemiology data and social
      deprivation data. Calculation of electoral ward dental registration rate using
      health authority population register data and dental practice board data.
      SETTING: Within a health authority using population data already held by the
      health authority. RESULTS: Children living in deprived wards are 1.5 times as
      likely to have experienced decay (47% versus 31%). Of those children with decay,
      children in deprived wards have more teeth which have experienced decay (mean
      dmft (dmft > 0) 5.4) and more untreated decay (mean dt (dmft > 0) 3.4) compared
      with their peers in less deprived wards (mean dmft (dmft > 0) 4.6 and mean dt
      (dmft > 0) 3.1). Dental Practice Board data is based upon dental practice
      postcode, hence some Sheffield electoral wards have dental registration levels as
      high as 1400 per 1000 residents. CONCLUSIONS: The principle of targeting dental
      need by use of Jarman Score is appropriate, however the targeting is undermined
      by the use of dental practice postcode as the basis of payments. Payment should
      be based upon the home postcode of the child patient.

PMID- 10205972
TI  - Self-reporting of periodontal health status.
AB  - OBJECTIVE: The objective was to develop a self-reporting questionnaire for use as
      an epidemiological measure of periodontal status. DESIGN: Oral survey. SUBJECTS
      AND METHODS: 100 (out of 102 who were approached) non-referred patients attending
      Dundee Dental Hospital and School agreed to complete a questionnaire concerning
      factors related to periodontal disease and then undergo a standardised
      periodontal examination in which four indicators were measured: the percentage of
      sites with plaque, the percentage of sites which showed bleeding on probing,
      tooth mobility and Community Index of Periodontal Treatment Needs scores. MAIN
      OUTCOME MEASURE: Sensitivity and specificity of questionnaire items to predict
      clinically measured periodontal disease indicators. Acceptable levels for
      sensitivity and specificity are largely dependent on the context of the test
      being evaluated, and many tests currently used in dentistry have very low
      sensitivity or specificity values. Nevertheless, in this case it was felt that
      any items which had a sensitivity and specificity greater than 0.80 would be
      reasonable predictors. RESULTS: Only four items were weakly predictive of the
      periodontal status indicators (sensitivity and specificity > 0.5). These
      concerned noticing gaps between teeth getting bigger, noticing tooth roots
      becoming more visible, experiencing pain when consuming hot, cold or sweet things
      and smoking. Other items, concerned with whether a dentist had told the patient
      they had periodontal disease or whether the person was aware of being treated for
      it, had very low sensitivities suggesting that people with periodontal disease
      indicators are failing to be informed of, or treated for it, by their dentist.
      CONCLUSIONS: Self-reporting of periodontal health was not successful as many
      people who had some indications of the periodontal diseases appeared to be
      unaware of their condition and also appeared not to have been informed nor were
      being treated for it.

PMID- 10205973
TI  - An investigation of the effects on children of tooth extraction under general
      anaesthesia in general dental practice.
AB  - OBJECTIVE: To describe the morbidity related to general anaesthesia provided in
      general dental practices for the extraction of teeth in school children. DESIGN:
      Observational study supported by structured questionnaires and interviews.
      SETTING: Three general dental practices in a Lancashire health district and
      children's homes. SUBJECTS: 80 children aged 5-15 years undergoing extractions
      under general anaesthesia. MAIN OUTCOME MEASURES: Observed demeanour of the
      children prior to, during and immediately after the surgical procedures. Reported
      morbidity during the following 24 hours and 1 month later. RESULTS: 92% of the
      children complained of symptoms associated with the surgery under general
      anaesthesia. Distress was noted in 16 (20%) patients during the induction of 26
      (33%) during recovery. Continued crying was reported for 24 (39%) during the
      journey home and for 23 (37%) once home had been reached. Other symptoms included
      nausea, vomiting, sickness and prolonged bleeding. Six reported psychological
      trauma 1 month after; three had nightmares, two had continuing bad memories and
      one was depressed for several days. CONCLUSION: Morbidity following extractions
      under general anaesthesia in general dental practice is common and has
      distressing consequences for the young patients and their carers.

PMID- 10205974
TI  - Can I explain?

PMID- 10205976
TI  - Outbreak of Vero cytotoxin producing Escherichia coli O157 infection in north
      Cumbria.

PMID- 10205977
TI  - Allergic reactions to ciprofloxacin chemoprophylaxis.

PMID- 10205978
TI  - Serious hazards of transfusion (SHOT)--annual report 1997-1998.

PMID- 10205979
TI  - The national measles surveillance strategy. The National Centre for Disease
      Control Measles Elimination Advisory Committee.

PMID- 10205980
TI  - Implementing a system of enhanced surveillance for measles in Victoria. The
      Enhanced Measles Surveillance Working Party.
AB  - In response to identified deficiencies in the passive surveillance system for
      measles in Victoria and the move towards local disease elimination and global
      disease eradication, a system of enhanced measles surveillance was introduced in
      1997. Each case is contacted and a structured telephone questionnaire is
      completed, collecting information on symptomatology and encouraging serological
      confirmation, if not already performed. The introduction of a paediatric
      phlebotomy service to collect serum specimens in the case's home, has led to a
      dramatic increase in the proportion of cases where testing is performed, reaching
      nearly 90 per cent by the end of 1998. The median time from notification to
      specimen collection is one day. The Victorian approach to the enhanced
      surveillance of measles provides a framework for similar systems as Australia
      approaches disease elimination.

PMID- 10205981
TI  - Surveillance data in CDI.

PMID- 10205982
TI  - Communicable diseases surveillance.

PMID- 10205984
TI  - [The relationship between the length of orthodontic treatment and patient
      compliance].
AB  - Based on the results of the psychological tests and their clinical experience,
      the authors conclude as follows: 1. At the beginning of the orthodontic treatment
      the fear of the unknown is dominating, but later on the aesthetic desires gain
      more importance than the first reaction. 2. The compliance and the length of the
      orthodontic treatment show an indirect proportional relationship. The compliance
      is stronger in case of a shorter and more successful orthodontic treatment.

PMID- 10205983
TI  - [Laboratory and clinical investigation of multifunctional dentifrices. Clinical
      study of a new triclosan-containing toothpaste].
AB  - The purpose of this work was to assess the in vitro antibacterial effectiveness
      of three dentifrices containing antimicrobial agents and to test the in vivo anti
      plaque and anti gingivitis effect of a toothpaste containing triclosan (CAOLA).
      The in vitro tests showed a marked antibacterial effect of both triclosan and
      chlorhexidine containing dentifrices. The randomized clinical trial presented
      good evidences that the triclosan had some but statistically non significant
      plaque and gingivitis reduction in patients even without previous mechanical
      cleaning. Nevertheless the triclosan dentifrice was effective in reducing the
      plaque and gingivitis scores in combination with initial mechanical debridement
      and oral hygienic instructions.

PMID- 10205986
TI  - Experimental studies: randomized clinical trials.
AB  - There are two major approaches to medical investigations: observational studies
      and experimental trials. The classical application of the experimental design to
      studies of human populations is the randomized clinical trial of the efficacy of
      a new drug or treatment. A further application of the experimental studies is to
      the testing of hypotheses about the etiology of a disease, already tested and
      corroborated from various forms of observational studies. Ethical considerations
      and requirements for consent of the experimental subjects are of primary concern
      in the clinical trials, and those concerns set the first and final limits for
      implementing a trial. General moral principles in research with human and animal
      beings, defined by the "Nuremberg Code," deal with strict criteria for approval,
      endorsement and evaluation of a clinical trial.

PMID- 10205987
TI  - Breast cancer and barrier contraception: postulated and corroborated potential
      for prevention.
AB  - A case-control study and a number of ecological surveys have been conducted in
      order to test the hypothesis that a reduced exposure to human semen factors
      during the reproductive lives is an etiological risk factor in the development of
      breast cancer in married women. The results of the retrospective study, carried
      out jointly at two universities in the USA during 1974-1978, corroborate the
      postulated association between the use of barrier contraception (condom or
      withdrawal) and the breast cancer development in women. The sequential surveys of
      the last 20 years provided ecological evidence of the predicted and anticipated
      natural experiment, the epidemic rise of breast cancer internationally during the
      decades of 1980s and 1990s, and further corroborated the potential for a primary
      (non-chemical) prevention of breast cancer in the community.

PMID- 10205985
TI  - [In vitro comparison of marginal adaptation of various filling materials. I.
      Effect of the filling material on marginal adaptation].
AB  - In a two-month in vitro experiment cervical marginal adaptation was examined in
      relation to the preparation, filling method and restorative material. Fifty Class
      II cavities were prepared in fifty extracted sound human premolar and molar teeth
      extending to the approximal cement-enamel junction. The cavities to receive
      composite restorations were bevelled at the vestibulo-occlusal and -approximal
      enamel margins, the other aspects of the cavity enamel and gingival margins at
      the cement-enamel junction being prepared conventionally. The cavities for
      amalgam were prepared and filled conventionally. The specimens were cycled in
      different buffer solutions and temperature, modelling possible variations in the
      oral environment and examined with SEM. The results were analysed using ANOVA.
      The best marginal adaptation among the composites was achieved with Charisma,
      Estilux Posterior, Durafil and Prisma AP. H at the bevelled enamel margins, the
      worst marginal fit was with Heliomolar and Polofil. It was concluded, that
      adhesive technique reduces, but does not eliminate marginal leakage.

PMID- 10205988
TI  - Histochemical and ultrastructural criteria for early differentiation of human
      subcutaneous adipocytes.
AB  - The histochemical, enzyme-histochemical and ultrastructural characteristics of
      the adipocyte precursors in human embryos at 6-12 weeks of gestation were
      studied. Some consequent stages in the histogenesis and differentiation of the
      fat cells were maintained according to: 1/number and size of the lipid droplets;
      2/position of the nucleus. The cells become rounder, accumulate lipid inclusions,
      acquire eccentric nucleus, gradually gather in clusters. No typical unilocular
      adipocytes were seen at this stage of fetal development. The enzyme
      histochemistry disclosed that the reactions for glucose-6P-dehydrogenase, NADH2
      diaphorase and especially lipoprotein lipase were highly expressed.
      Ultrastructurally the adipocyte precursors were with a great amount of
      organelles/mitochondria of typical sight, well developed rough and smooth
      endoplasmatic reticulum/, lipid droplets and glycogen which express their high
      functional activity. This study could provide criteria for understanding the
      processes of lipidogenesis and differentiation.

PMID- 10205989
TI  - Ethosuximide inducted changes in the gastro-intestinal tract.
AB  - Ethosuximide is an alternative medicament that is used for coupling of petit mal,
      especially in childhood. Some clinical observations show that it has secondary
      effects on the gastro intestinal tract (GIT). The present research tries to
      define the characteristics of Ethosuximide--the inducted secondary effects on the
      GIT, and to explain some of the possible mechanisms that cause them. The changes
      that occur in the GIT of patients cured with Ethosuximide are registered
      roentgenologically. The main change is the atony of the stomach and intestines
      and the reduced peristaltic activity. The influence of Ethosuximide is examined
      on smooth muscular samples of human stomach, taken in vitro using stomach
      resection. The medicament authoritatively reduce the spontaneous bioelectrical
      activity of the smooth muscular tissue, influences mainly it's components that
      have Ca+ nature. Together with that is indicated relaxation of the smooth
      muscular samples. In that research is expressed the thesis that this Ethosuximide
      reduction of the Ca(+)-influx in the smooth muscular cells and the related
      relaxation probably are one of the main reasons of the secondary effects on the
      GIT.

PMID- 10205990
TI  - Learning effect in automatic static perimetry with Dicon TKS 4000 computed
      perimeter.
AB  - To find out the significance of the learning effect in repeated computed
      perimetry. We performed computed perimetry twice within one week period on 35
      eyes (20 patients) with suspected glaucoma and visual acuity > 0.5 (20/40). The
      program used was with 30 degrees threshold grid. For each quadrant of the visual
      field were recorded the mean deviation readings. These readings were compared for
      the initial and the second perimeters for each eye. The mean deviation from the
      normal readings were significantly higher for the initial perimetric exam for all
      quadrants (Wilcoxon test for matched pairs, p < 0.05). The visual field defects,
      if present, were more concentrated and with sharper borders in the second exams.
      This study suggests that there is a significant learning effect in computed
      perimetry. A visual field exam, showing defects suspicious for glaucoma, should
      be repeated within one week and the second one taken for further referral.

PMID- 10205991
TI  - Cardiopulmonary stress test--general characteristics and clinical value.
AB  - Dyspnea on exertion and exercise intolerance are common problems in many
      conditions and diseases. Cardiopulmonary exercise testing makes possible to
      assess the exercise response in patients with abnormalities which are either
      underestimated or not detectable at rest. The method permits simultaneous
      assessment of circulatory and ventilatory reserves and can determine aerobic
      capacity, anaerobic threshold, the ventilatory response and the appearance of
      hypoxemia. Peak exercise oxygen uptake is the variable most often used, because
      of its physiological and prognostic value. One can use this information to
      evaluate the nature and severity of disease, its progression over time and its
      response to therapy.

PMID- 10205992
TI  - Treatment of moderate or severe arterial hypertension with losartan.
AB  - Losartan is the first drug of a new class antihypertensive drags--Angiotensin II
      receptors antagonists. According to the data in the literature the drug shows a
      very good efficiency and tolerability. Fifteen patients at the average age of
      48.9 are the object of this study. Our study establishes considerable lowering of
      the systolic BP with 15.9% and of the diastolic BP with 20.3%. No considerable
      effects on the hematopoiesis, the carbohydrate and the lipid metabolism, and the
      renal function were observed during treatment with Cozaar.

PMID- 10205993
TI  - HbOThrace trait, HbOThrace hemoglobinopathy and HbOThrace/Hb beta zero
      hemoglobinopathy: a retrospective study of 118 cases.
AB  - HbOThrace is an abnormal hemoglobin which is constructed by defective beta chains
      (Glu121-->Lys121). It mostly characterises the Muslim minority of the Thrace
      region. During the last 6 years, our department detected HbOThrace in 118 cases.
      Four groups were formed, the first consisted of cases of HbOThrace trait with
      normal iron and ferritin levels, the second of cases of HbOThrace
      hemoglobinopathy, the third of cases of HbOThrace/Hb beta zero hemoglobinopathy
      and the fourth of cases of HbOThrace trait with low iron and ferritin levels. The
      second, third and fourth group were compared with the first one. The conclusion
      is that the presence of HbOThrace leads to a mild hypochromic anemia, with no
      clinical findings, but the coexistence of beta zero gene or iron deficiency
      produces more pronounced laboratory findings and even clinically evident anemia.

PMID- 10205994
TI  - The antiarrhythmic effect of adaptation to intermittent hypoxia.
AB  - There was shown an antiarrhythmic effect of adaptation to intermittent hypobaric
      hypoxia in ischemia, reperfusion, experimental infarction and postinfarction
      cardiosclerosis (F.Z. Meerson, 1988). These results was obtained in whole animal
      experiments. In our study it was demonstrated that the antiarrhythmic effect of
      adaptation to hypoxia persisted in hearts after isolation, in absence of the
      effect of neural and humoral factors on the organ. Adaptation of animals to
      intermittent hypoxia was produced by "stepwise" elevations in an altitude
      chamber: first day--1000 m; second day--2000 m; third day--3000 m and rest of the
      days--to 4000 m above sea level. The course of doses adaptation to hypoxia lasted
      for 40 days; each daily exposure lasted 5 hours. The analysis of arrythmogenic
      and contractural effects of hypercalcium perfusion and "calcium paradox"
      phenomenon shows a significant decrease of these effects in hearts of adapted
      animal. The bioelectrical activity investigation of papillary muscles
      cardiomyocytes, obtained from hearts of adapted animals, was shown, in
      hypercalcium perfusion condition, a complex of antiarrhythmogenic changes which
      was expressed in limitation of rest and action potentials decreasing and in
      maintenance of the action potential duration. In papillary muscles, obtained from
      adapted animals, the contracture and the depression of contractility was also
      smaller. In experiments on resting papillary muscles we found that adaptation to
      intermittent hypoxia significantly decreased contractural and depolarizing
      effects of low-sodium perfusion. Thus adaptation to intermittent hypobaric
      hypoxia resulted, at cardiomyocytes level, in a complex of antiarrhythmic changes
      which may indicate a protective effect of this kind of adaptation in cardiac
      arrhythmias.

PMID- 10205995
TI  - Late post-operative astigmatism after extracapsular cataract extraction and
      intraocular lens implantation.
AB  - The purpose of the study is to establish the amount of surgically induced
      astigmatism after extracapsular cataract extraction (ECCE) and intraocular lens
      (IOL) implantation. Eighty three eyes of 79 patients who had ECCE + IOL
      implantation were examined in the period between the 6th and the 16th month after
      the operation. The pre- and post-operative auto keratometry readings (K1 and K2)
      were recorded for each patient. These readings were compared between themselves,
      as well as with the post-operative cylinder power estimated by an autorefractor
      (total astigmatism). The mean pre-operative corneal astigmatism (K1-K2) was 1.00
      +/- 0.09 Dpt Cyl, and the mean post-operative -1.74 +/- 0.14 Dpt Cyl. The
      difference is statistically significant. The mean autorefractor cylinder power
      was 1.70 +/- 0.14 Dpt Cyl. It correlates strong with the post-operative corneal
      astigmatism. There is a moderate correlation between the degree of the post
      operative corneal and total astigmatism. The surgically induced corneal
      astigmatism is the main component of the total post-operative astigmatism after
      ECCE + IOL implantation. The total astigmatism is mainly with the rule (vertical
      plus cylinder) and it does not seem to impair severely the post-operative visual
      acuity of the patients.

PMID- 10205996
TI  - Treatment of bleeding oesophageal varices with endoscopic sclerotherapy--first
      results.
AB  - Patients with bleeding oesophageal varices represent 5% of cases of upper GIT
      bleeding. Varices develop and bleed as a result of portal hypertension which is a
      complication occurring in 30% of patients who suffer from chronic liver diseases.
      The mortality rate for the first bleeding episode is 50% and 30% for subsequent
      episodes. Almost 100% of those who survive the first episode, bleed again within
      the following two years. The risk of rebleeding is higher with varices increasing
      their number, length and extension, varices of III and IV degrees, portal
      pressure over 16 mm Hg. Despite of some recent advances the endoscopic
      sclerotherapy still remains the initial treatment of choice in patients with
      bleeding oesophageal varices. Authors report of having achieved control over
      bleeding in 80 to 90% of patients. Over the next few days of the same
      hospitalisation 10 to 20% of those patients rebleed and require a second sclero
      therapy session. When the latter fails in controlling the hemorrhage, the
      mortality rate is estimated as high as 100% which prompts more invasive surgical
      and radiological interventions.

PMID- 10205997
TI  - Female sex organs malignancies incidence in Plovdiv district for the period 1986
      1996.
AB  - The aim of the recent survey is to investigate the dynamics of female sex organs
      malignancies (carcinoma of the uterine corpus, cervical carcinoma and ovarial
      carcinoma) incidence and to make a structural analysis. The incidence of female
      sex organs malignancies increases every other year from 37.7 cases in 1986 to
      58.64 cases per 100,000 women in 1996. The cervical carcinoma incidence for that
      period increases from 8.1 cases in 1986 to 14.65 cases per 100,000 women in 1996.
      For the same period endometrial carcinoma incidence increases from 16.2 cases to
      24.74 cases per 100,000 and ovarial carcinoma incidence--from 13.0 cases to 19.64
      cases per 100,000. Malignancy staging is an important part of the study. Clinical
      stage I is diagnosed only in 25.28% of the new cases, stage II--in 46.02%, stage
      III--in 17.75% and, stage IV--in 10.95% of the cases. The incidence of female sex
      organs malignancies in the examined, regions and locations shows that there are
      some differences between the three regions of Plovdiv district (Plovdiv,
      Pazardjik and Smolyan). The region of Plovdiv has a highest incidence. There are
      also a differences in the incidence between the citizens of the town and the
      villages.

PMID- 10205998
TI  - Cyclicity in variations of incidence rates for breast cancer in different
      countries.
AB  - The aim was to analyze breast cancer (ICD9; Dx:174) in the view of studying and
      forecasting registration and incidence dynamics. Cycles in incidence rates for
      breast cancer in Bulgaria (1952-1985, period T = 17.63 and TH = 73.50 years) were
      restated. Patterns of annual incidence rates for different time stretches over
      the years 1964-1993 in the North West Region (NWR, UK), Ontario (Canada), USA and
      Bulgaria were compared. Monthly registration of new cases in NWR (1972-1993) and
      Bulgaria (1991-1994) was also analysed. Analysis of seasonality, non-linear
      regression, Fourier spectra, ARIMA and periodogram regression analysis with
      basic, detrended or decycled trigonometric approximations were applied. Cyclic
      variations in incidence for NWR (T = 10.25 years, p < 0.05), Ontario (T = 17.75
      years, p < 0.05) and USA (TH = 20.50 years, p < 0.05) were revealed and previous
      findings confirmed. The cycle of 20.50 years for USA was considered a single
      "first-degree hypercycle" (n = 17 years). A stable "hypercycle" was found only
      for NWR (TH = 44 years, p < 0.01) describing a long-term cyclic trend. Short-term
      cyclicity for registrations in NWR (T = 4, 7.5 and 10.5 months, p < 0.05) and
      Bulgaria (T = 3, 6 and 11.5 months, p < 0.05), with peaks in March and June-July
      for both countries and a peak in October for NWR (all at p < 0.05), was also
      revealed. Cyclicity in occurrence might contribute to better understanding of
      breast cancer epidemiology and promote creation of more accurate predictive
      models. The lack of stable "hypercycles" in variations of incidence rates for USA
      and Ontario, for example, might be seen as an indicator of effectiveness of
      screening and/or influence of risk factors.

PMID- 10205999
TI  - Sexual culture of gypsy population.
AB  - The number of the gypsy population in Bulgaria has increased with 85,419 persons
      for the period 1965-1992 that is higher than the prognosis made about a mean rate
      of increase of 2000 persons per year. The aim of the present study was to
      describe demographic changes and main problems of intrafamily planning of this
      population. The primary information was collected by the method of indirect
      individual inquiry as the opinion of 495 gypsy women at reproductive age was
      studied. Sexual behaviour of this ethnic group was analysed with the needs and
      social, economical and cultural status. The results have revealed particular
      patterns of the sexual behaviour about the beginning of early sexual
      relationships, use of modern contraceptive methods, number of abortions, etc. It
      should be noted that only about 61% from the gypsy women use any kind of
      contraceptive measures but irregularly. The mean number of abortions per woman
      was 2.41 and about 33% of women had undergone 3 and more abortions-on-demand. The
      low level of sexual culture and the lack of knowledge about the methods of
      contraception have led to early first births, high proportion of abortions-on
      demand and high rate of increase of the population among gypsies. This may be
      explained by the life-style traditions of this ethnic group and their intention
      to the multi-child model of the family. We must emphasize the lack of modern
      information system for early warning, publicity and formation of sexual habits of
      this population.

PMID- 10206000
TI  - Logistic analysis of adaptive gender variants of smoking youths behavior.
AB  - The objective of this study was to analyze some specific features of adolescent
      smokers' self-perception and general attitude to living. All students of a highly
      qualified secondary school in Stara Zagora were asked to fill in a prepared
      especially for the study, self-completed questionnaires. Response rate was 79% (n
      = 174). Logistic analysis was used in order to describe abstract tendency of the
      direct significant evidences. The data were found that smoking youths had more
      emphasized emotional and sensual motives and stereotypes. This predisposes them
      to wrong behavioral decisions and smoking probably is one of the harmful results
      of such irrational approach.

PMID- 10206001
TI  - Assistance with generalized net models to the differential diagnosis of some
      pathologic somatic muscular and neurologic conditions in stomatology.
AB  - Some somatic pathologic muscular and neurologic conditions in stomatology are
      difficult to differentiate. For example, the myofascial pain dysfunction
      syndrome, trigger point muscle pains and a number of temporomandibular joint
      related pathoses often cause diagnostic difficulties. With the purpose to assist
      general clinicians and students to understand and differentiate more easily these
      difficult occasions, the authors try to offer a model simulating the decision
      making process in some of the aforementioned pathoses. The model is based on the
      Generalized Nets Models which represent extensions of Petri's nets and their
      modifications.

PMID- 10206002
TI  - Incidence of dental caries /Is/ on milk molars /M1,M2/ in 3-8 year-old children
      from Plovdiv.
AB  - The incidence of dental caries /Is/ on deciduous molars in 1216 children aged 3
      to 8 from Plovdiv has been studied. The results showed highest Is in the fissures
      of m1 and m2 and lowest Is on the smooth surfaces. The incidence of dental caries
      is getting higher with statistically significant differences in the lower jaw up
      to the 6th year and in the upper jaw up to 7th year of age. Is in the lower jaw
      is higher than that of the upper jaw only in the fissures.

PMID- 10206004
TI  - A method with combined prosthetic treatment of mandible with lateral resection
      and exarticulation.
AB  - A part of the people who need prosthetic treatment in the maxillofacial area are
      in the stage of after-surgical operation of tumors. One of the most commonly
      discovered defects in the mandible is the lateral resection with exarticulation.
      Our goal is to examine the possibilities of achieving optimal prosthetic
      restoration of the patients with lateral resection and exarticulation of the
      mandible through clinical application and combination of the modern technology
      and supportive-retentioned elements.

PMID- 10206003
TI  - Assessment of the behaviour of Bulgarian children dental patients at the age of 4
      12.
AB  - The behaviour of Bulgarian children dental patients at the age of 4-12 has been
      studied by application of Venham's 6--grade behaviour scale. A sample of 274
      clinically healthy children, divided in 3 age groups, were the object of the
      study. It has been found that the number of children whose behaviour has been
      assessed as one within the norm, is much greater that the number of the rest of
      patients-amounting to 77.74% and their number increasing with age. The negative
      behaviour, regardless of its rate, is not influenced by age.

PMID- 10206005
TI  - Denture possibilities for patients with mental disorders.
AB  - Patients with mental disorders, due to their specific physical and social status,
      often lack the possibility for appropriate dental treatment. The objective of our
      study aims at creating an adequate approach and prospective for currative plan
      casual. We represent two clinical cases, treated in a different way and we
      conclude, that every separate patient requires individual approach, from the
      first contact, through diagnosing and decision making for plan of treatment. Our
      experience implies that the mental status of the patients is not a reason for
      refusal of dental treatment.

PMID- 10206006
TI  - The application of modern light-curing radiopaqie glass ionomer composites to the
      apical osteotomy.
AB  - The report reveals the application of modern light-curing radiopaque glass
      ionomer composites as a retrograde filling substance in the aplical osteotomy.
      The excellent results after 20 apical osteotomies which have been observed in the
      course of 3 years, prove the real possibility of using them in the dental
      surgery.

PMID- 10206007
TI  - Nephroblastoma in experience of pediatrics clinic from Cluj-Napoca between 1974
      1997--a clinical and anatomopathological approach.
AB  - Based on a retrospective analysis of 60 cases of nephroblastoma, the author
      reaches the following conclusions: 1) correct diagnosis and treatment of the
      nephroblastoma depend on the team-work involving the surgeon, the chemotherapist
      and the pathologist; 2) during the macroscopic analysis the pathologist is asked
      to: establish/determine if the tumor penetrates the renal capsule, establish the
      tumor invasion into the renal sinus vessels, establish if the medial limit of the
      renal sinus is occupied or not by the tumor and, include the nephrectomy
      specimens in the category over or below 550 g; 3) during the microscopical
      analysis the pathologist is asked to: actually make the positive diagnosis of
      nephroblastoma, identify the presence or the absence of the diffuse or focal
      anaplasia; and 4) based on this data the surgeon will complete the staging while
      the chemotherapist will choose a certain protocol depending on the stage and on
      the presence or absence of the anaplasia.

PMID- 10206008
TI  - Central effects of AC-1 and TFG-1.
AB  - AC-1 and TFG-1 are both herb extracts from Avena Sativa and Trigonella Foenum
      Graecum respectively. In folk medicine, Trigonella Foenum Graecum is used as
      appetiser and general tonic as well as for pellagra treatment and for treatment
      of pulmonary disorders. Avena Sativa is another commonly used appetiser and
      tonic. In our study we examined the influence of AC-1 and TFG-1 on some of the
      major functions of the central nervous system. We divided the test animals in
      three groups and after administering the herb extracts we monitored different
      pharmacological parameters-Phenamine toxicity and stereotypy, Hexobarbital sleep,
      elementary conditioned reflexes and antiseizure activity.

PMID- 10206009
TI  - An inquiry survey on the level of dental health knowledge about caries
      prophylaxis among 12-year old pupils in Plovdiv, Bulgaria.
AB  - The main purpose of this inquiry is to reveal the presence of health culture and
      skills concerning oral health of children to determine their preferences about
      the forms of dental health education. This will contribute to develop a national
      strategy for health education in the future with up-to-date methods and means.

PMID- 10206010
TI  - Rearrangement of T-cell receptor and immunoglobulin heavy chain genes in leukemia
      and lymphoma.
AB  - The development of polymerase chain reaction /PCR/ has greatly facilitated the
      detailed characterization of T-cell receptor /TcR/ and immunoglobulin heavy chain
      /IgH/ gene rearrangements. The antigen-receptor genes in lymphoid cells undergo
      rearrangements by combination of variable /V/, diversity /D/ and joining /J/ gene
      segments, deletion of germline nucleotides and insertion of nontemplate-derived
      nucleotides /"N-regions"/. In this preliminary study we analysed 12 DNA samples
      from patients with lymphoproliferative disorders /LPD/ and with acute
      nonlymphoblastic leukemias /ANLL/. PCR analyses were performed using V and J
      consensus primers for conserved regions of TcRg and IgH genes. PCR products were
      evaluated by polyacrilamide gel electrophoresis and denaturing gradient gel
      electrophoresis. Applying this method, we have detected 3 TcRg and 4 IgH
      monoclonal rearrangements in all 12 LPD samples. One ANLL sample showed
      monoclonal rearrangement for TcRg. Because of the clonal rearrangements, the
      analysis of TcR and IgH gene configuration can be used to track the persistence
      of malignant cells which are determined at diagnosis. The positive results from
      ANLL samples will be further evaluated as prognostic criteria.

PMID- 10206011
TI  - Prognostic assessment of the Durie and Salmon staging system in patients with
      multiple myeloma.
AB  - In a prospective study, covering a 10-year period, 109 patients with multiple
      myeloma (56 men and 53 women of mean age of 62) were followed. The patients were
      grouped according to the staging system of Durie & Salmon. They were treated
      uniformally with monochemotherapy with Cyclophosphamid, Melphalan and
      Glicocorticosteroids. The median survival for the different clinical stages was:
      I--53 months, II--31 and III--24 months. Significant difference between stages II
      and III with 98 patients (89.9%), was not found. Authentically, patients in II A
      compared to II B clinical stage had higher median survival of 40 and 26 months,
      respectively. So was IIIA compared to IIIB--38 and 18 months. It was found that
      the prognosis for the life expectancy of the patients depended to a greater
      degree on the extent of the renal function impairment at the time of diagnosis of
      the process, e.g., on the A and B substage (serum creatinin level > 160 mmol/l)
      than on the size of the tumour mass, respectively the clinical stage according to
      Durie & Salmon system.

PMID- 10206012
TI  - Gastroesophageal reflux in children with cystic fibrosis.
AB  - The aim of the study is to reveal the frequency of gastroesophageal reflux /GER/
      in children with cystic fibrosis /CF/ and the possibilities of GER's management.
      Twelve children with CF were monitored for GER by 24-hour pH monitoring of the
      distal part of the oesophagus, according to the instructions of ESPGAN with
      Digitrapper MK III, at the time of clinical remission of pulmonary involvement.
      All patients with diagnosed GER were treated with 10 mg. Cisapride an hour after
      dinner. GER was proven in 7 children older than 6 years, only while asleep and
      with no correlation with the time of inhalations. Treatment for GER was safe and
      effective.

PMID- 10206013
TI  - Clinical economics in clinical trials: the measurement of cost and outcomes in
      the assessment of clinical services through clinical trials.
AB  - As the population ages and more expensive high-technology services become
      available, health care costs continue to spiral upward. Because the financial
      resources for health care are limited, economic analysis can help to evaluate
      expenditures and set priorities. Economic analysis of medical technology or
      medical care evaluates a medical service by comparing its dollar cost with its
      dollar benefit (cost-benefit), by measuring its dollar cost in relation to its
      outcomes (cost-effectiveness) as well as in relation to its utility or quality
      adjusted outcomes (cost-utility), or simply by tabulating the costs involved
      (cost-identification). Direct costs are generated as services are provided. In
      addition, patients' productivity is affected, and these costs can be considered,
      especially in determining the benefit of a service that decreases morbidity or
      mortality. Intangible costs are those of pain, suffering, and grief. The point of
      view, or perspective, of the study determines the costs and benefits that will be
      measured in the analysis. Sensitivity analysis, which can evaluate the stability
      of the conclusions to the data used, is an important assessment within economic
      analysis. Economic analysis of new pharmaceutical therapies is increasingly being
      incorporated into clinical trials. Although there are some limitations of
      pharmacoeconomic information in clinical studies of drug safety and efficacy,
      these trials are often the only opportunity for economic data collection before
      adoption and reimbursement decisions are made. Validation after the drug has been
      introduced should complement economic information developed from clinical trials.

PMID- 10206014
TI  - Molecular biology and reproduction.
AB  - Modern molecular biology has provided unique insights into the fundamental
      understanding of reproductive disorders and the detection of microorganisms. The
      remarkable advances in DNA diagnostics have been expedited by the development of
      polymerase chain reaction (PCR) and the ability to isolate DNA and RNA from many
      different sources such as blood, saliva, hair roots, microscopic slides, paraffin
      embedded tissue sections, clinical swabs, and even cancellous bone. These
      technical advances have been bolstered by the development of an increasing number
      of effective screening techniques to scan genomic DNA for unknown point
      mutations. The continued development of technology will ultimately result in
      automated DNA (desoxyribonucleic acid) diagnosis for the practicing clinician.
      The continuing expansion of information concerning the human genome will place an
      increasing emphasis on bioinformatics and the use of computer software for
      analyzing DNA sequences. With the automation of DNA diagnosis and the use of
      small samples (500 nanograms), the direct examination of the DNA of a patient,
      fetus, or microorganism will emerge as a definitive means of establishing the
      presence of the specific genetic change that causes disease. A knowledge of the
      precise pathology at the molecular level has and will provide important insights
      into the biochemical basis for many human diseases. A firm knowledge of the DNA
      alterations in disease and expression patterns of specific genes will provide for
      more directed therapeutic strategies. The refinement of vector technology and
      nuclear transplantion techniques will provide the opportunity for directed gene
      therapy to the early human embryo. This presentation is designed to acquaint the
      reader with current techniques of testing at the DNA level, prototype mutations
      in the reproductive sciences, new concepts in the molecular mechanisms of disease
      that affect reproduction, and therapeutic opportunities for the future. It is
      hoped that future refinement of these techniques combined with the ability to
      maintain genetic modification of these cells with recombinant vector technology
      will provide a definitive therapy for many single gene disorders, such as sickle
      cell anemia and thalassaemia. It is truly the challenge of the next century to
      decipher how these legions of newly discovered genes work, and to create a
      molecular language that can extend across all organisms.

PMID- 10206015
TI  - A new concept of skin-associated lymphoid tissue (SALT): UVB light impaired
      cutaneous immunity reveals a prominent role for cutaneous nerves.
AB  - More than 20 years have passed since the concept that the skin has its own
      associated immune system was first proposed by Streilein. This proposal was
      advanced in part on evidence that cutaneous contact hypersensitivity (CH)
      reactions are closely correlated with Langerhans cells (LC). Recent reports have
      demonstrated that LC have neural connectivity with cutaneous nerve termini
      containing calcitonin gene-related peptide (CGRP), suggesting that a link exists
      between innervation and immune responses in the skin. Here we discuss the neural
      components which have recently been found to be participants in skin-associated
      lymphoid tissue (SALT). In part, discovery of a functional link between the
      nervous system and SALT is based on studies in which cutaneous immunity was
      impaired by ultraviolet-B radiation (UVR). The deleterious effects of UVR on
      cutaneous immunity include failed CH induction and promotion of hapten-specific
      tolerance, effects that are mediated by tumor necrosis factor-alpha and
      interleukin-10, respectively. The source of these cytokines after UVR appears to
      be dermal mast cells. Evidence indicates that mast cells are triggered to release
      these cytokines in response to CGRP, which is released from UVR-damaged cutaneous
      nerve endings. Moreover, a substance P agonist was able to reverse the
      deleterious effects of UVR on CH induction, rendering the mice able to develop
      intense CH. These observations indicate that two cell types not originally
      included in the SALT concept are critical to the functional integrity of
      cutaneous immunity: mast cells and cutaneous nerves. We propose that cutaneous
      nerves dictate whether antigen applied to or arising within skin will lead to
      sensitivity or tolerance.

PMID- 10206016
TI  - The natural history of the systemic inflammatory response syndrome and the
      evaluation of SIRS criteria as a predictor of severity in patients hospitalized
      through emergency services.
AB  - Based on the concept of the systemic inflammatory response syndrome (SIRS), a one
      year retrospective study was carried out among a total of 2389 patients
      transported to the emergency room by ambulance. With respect to 351 patients who
      had all data necessary for evaluating SIRS criteria in 369 hospitalized patients,
      200 met SIRS criteria within 24 hours of admission (24h-SIRS). The mortality rate
      for 24h-SIRS patients was significantly higher than that of non-SIRS patients.
      The mortality rate for 24h-SIRS patients increased sequentially as more SIRS
      criteria were met. In 235 patients who met SIRS criteria during hospitalization
      (overall-SIRS), 108 had sepsis. Of these, 60 developed severe sepsis, and 50
      developed septic shock. The mortality rate for patients who had 3 or more
      consecutive days of SIRS was significantly higher than that for those with less
      than 3 consecutive SIRS days. Among 153 patients who had all data necessary for
      APACHEIII scoring within 24 hours of admission, the mortality rate for SIRS
      patients whose APACHEIII score was 50 or higher was 40.7%, significantly higher
      than that of other patients. In conclusion, SIRS criteria were demonstrated to be
      useful as indicators of severity and for predicting outcome in patients
      hospitalized through emergency services. Patients who met the following criteria
      were found to be a high-risk population among hospitalized emergency patients
      with SIRS: (1) Those who had three or more consecutive days of SIRS. (2) Those
      whose APACHEIII score was 50 or higher.

PMID- 10206017
TI  - Physiological effects of modified hemoglobin as an oxygen-carrying macromolecule.
AB  - A stabilized hemoglobin as oxygen-carrying macromolecules was developed. It had
      approximately 90,000 dalton molecular weights and its intravascular half life was
      36 hours. Its molecular size was less than 0.1 micron. Its hemoglobin
      concentration was 6% and P50 value was 24 mmHg. The oxygen carried inside the
      plasma performs differently than the oxygen carried inside the red cells. Only
      less than 0.3 ml of oxygen in 100 ml of blood is available inside the plasma
      while 14-19 ml of oxygen is carried inside the red cells. Thus, less than 5 ml of
      oxygen is available inside the plasma of the entire body. When a patient develops
      hypovolemic shock, the red cells are bypassed and are not perfused directly
      inside the tissues. However, the plasma should reach such hypoxic tissues. Thus,
      infusion of oxygen-carrying macromolecules in the plasma should be
      therapeutically effective even if less than 100 ml of stabilized hemoglobin
      solution were infused under shock conditions. The basic physiology of oxygen
      carrying macromolecules is described in detail, which is different from the
      oxygen carried inside the red cells.

PMID- 10206018
TI  - An HIV autopsy--characterization of zidovudine-resistant subtype E HIV-1 from
      autopsy tissue suggests the route of infection and an alternative protocol of
      therapy.
AB  - This CPC concerns a 47-year-old male patient with acquired immunodeficiency
      syndrome (AIDS). The patient became symptomatic when he developed Pneumocystis
      carinii pneumonia, but recovered sufficiently to be treated as an outpatient. Two
      years after falling ill, he developed septic shock and died within a short time.
      During this period, he failed to respond to HIV drugs, and there was no
      improvement in his immunodeficient status. The HIV retrieved from the patient's
      organs at autopsy was found to be type E and to have acquired resistance to
      Zidovudine. It was also possible to determine the route of infection. HIV
      treatment guidelines are continuously being revised on the basis of HIV research
      and the development of new treatment plans, and at the present time, when no
      definitive method of treatment has yet been established, it is essential for the
      clinician to keep abreast of the latest information. Since HIV patients are
      compromised hosts, it is important to diagnose and treat other infectious
      complications, not only complications unique to AIDS, and we have briefly
      described the latest HIV therapy.

PMID- 10206019
TI  - [General classification of hemostasis].

PMID- 10206020
TI  - [Management of quantitative and qualitative platelet defects].

PMID- 10206021
TI  - [Hereditary thrombophilia].

PMID- 10206022
TI  - [Antiphospholipid antibody syndrome].

PMID- 10206023
TI  - [Heparin in anesthesia. Pharmacological and clinical aspects in the prophylaxis
      of venous thromboembolism].

PMID- 10206024
TI  - [Oral anticoagulants].

PMID- 10206026
TI  - Coagulation and fibrinolysis in sepsis.

PMID- 10206025
TI  - [Elective surgery and emergency surgery in patients undergoing oral anticoagulant
      therapy].

PMID- 10206027
TI  - [Disseminated intravascular coagulation. Diagnosis].

PMID- 10206028
TI  - [Antithrombin III in intensive therapy].

PMID- 10206029
TI  - [Hemostasis and coagulation during major liver surgery and during orthotopic
      liver transplant].

PMID- 10206030
TI  - [Coagulation in heart transplant operations and in operations for applying
      ventricular assistance devices].

PMID- 10206031
TI  - [The importance of an "indexed" journal].

PMID- 10206032
TI  - Effects of speed of intrathecal injection on unilateral spinal block by 1%
      hyperbaric bupivacaine. A randomized, double-blind study.
AB  - BACKGROUND: To evaluate if the speed of intrathecal injection affects the lateral
      distribution of spinal block during unilateral spinal anaesthesia with 1%
      hyperbaric bupivacaine. METHODS:  DESIGN: prospective, randomized, double-blind
      study. SETTING: anaesthesia Department at a University Hospital. PATIENTS: 30 ASA
      physical status I-II patients, scheduled for elective orthopedic surgery
      involving one lower limb only (ankle and foot surgery). INTERVENTIONS: after
      placing the patients in the lateral decubitus position with the site to be
      operated on dependent, dural puncture was performed at L3-L4 interspace using a
      25-Gauge Whitacre spinal needle. After the needle hole had been turned toward the
      dependent side, patients were randomized to receive 8 mg of 1% hyperbaric
      bupivacaine injected over either 40 sec (Group SLOW, n = 15) or 3 sec (Group
      FAST, n = 15). The lateral position was maintained for 15 min. MEASUREMENTS: a
      blind observer evaluated the evolution of sensory (pinprick test) and motor
      (modified Bromage scale) blocks on both the dependent and nondependent sides
      until the regression of motor block by one degree. RESULTS: No differences in the
      maximal sensory level on both the dependent and nondependent sides were observed
      in the two groups. Unilateral sensory block was onserved in 6 patients in group
      SLOW (40%) and in 5 patients in group FAST (33%), (p = not significant[NS].
      Unilateral motor block was observed in 9 patients in group SLOW (60%) and in 10
      patients in group FAST (66%) (NS). CONCLUSIONS: Extremely reduced speeds of
      intrathecal injection did not improve the lateral distribution of spinal block
      when injecting 8 mg of 1% hyperbaric bupivacaine through a pencil-point
      directional spinal needle.

PMID- 10206033
TI  - Minimal flow and half-closed system ventilation in lung surgery.
AB  - BACKGROUND: This study aimed at determining the applicability of minimal flow
      anaesthesia in lung surgery. METHODS: The standards anaesthesiological technique
      was modified to perform minimal flow half-closed system ventilation. For
      procedures on left lung orobronchial intubation was performed by a White no. 41
      and no. 39 orotracheal tube, respectively in male and in female patients, in
      order to achieve a perfect tight of bronchial cuff and prevent gas loss from the
      circuit, because of the greater calibre of the right stem bronchus. The metal
      double lumen connector was replaced by a plastic tube that is clamped to exclude
      the lung from ventilation, whenever necessary. Fibrin glue was systematically
      applied on the bronchial stump or resected lung tissue before restoring
      ventilation. RESULTS: No significant changes were recorded in heart rate,
      arterial systolic and diastolic pressure, end-expiratoy CO2 concentration, oxygen
      saturation, airways maximum and minimum pressure. CONCLUSIONS: Minimal flow half
      closed system ventilation can be easily performed also in pulmonary surgery
      provided that gas loss from the circuit is 50 ml/min by means of specific
      technical adjustments.

PMID- 10206034
TI  - [Preemptive analgesia or balanced periemptive analgesia?].
AB  - "Preemptive analgesia" means that analgesia given before the painful stimulus
      prevents or reduces subsequent pain. The concept of preemptive analgesia
      originates from basic science and experimental studies. However, in some clinical
      studies preemptive effect is not always present. The authors think that it
      happens for: differences among experimental models and clinical reality, wrong
      use of some pharmacological knowledges, some methodological errors in clinical
      research. The authors analyze these factors and review in a critical manner
      clinical studies on preemptive analgesia. In some operations, only one
      administration of an analgesic drug, before surgery, is not sufficient to produce
      an evident preemptive effect. Postoperative pain can be reduced making a
      pharmacological treatment before surgery, for the whole time of painful stimulus.
      For this reason, the term "preemptive analgesia", like "analgesia given before
      surgery" is not adequate. The authors suggest that the concept of prevention of
      postoperative pain is well defined by the term of "balanced periemptive
      analgesia"; it is a new approach that use many modalities of analgesia in
      different times to prevent and control painful stimulus for the whole time of its
      origin: before and/or during operation and, if necessary, in the postoperative
      period for the residual pain.

PMID- 10206035
TI  - [Incidence of thrombi in implantation of pulmonary artery catheters].
AB  - AIM: To evaluate the occurrence of thrombi in introducers employed for pulmonary
      artery catheterization. DESIGN: prospective study. SETTING: cardiac Surgery ICU
      in a University Hospital. PATIENTS: three groups of 20 subjects each: in group A,
      undergoing mitral or aortic valve replacement, a pulmonary artery catheter was
      placed through an introducer; in group B, undergoing myocardial
      revascularization, a pulmonary artery catheter was placed through an introducer;
      in group C, undergoing myocardial revascularization, only an introducer was
      placed. METHODS: The introducers were removed between the 2nd and the 8th
      postoperative day and the external surface and the lumen were inspected for
      thrombi. RESULTS: Endoluminal thrombi were observed in 40% of the introducers,
      but the patency of the lumen was always maintained. The incidence of thrombi was
      significantly higher in group A (23% in aggregate) than in group B (10%; p <
      0.05) and in group C (6%; p < 0.05); by contrast no significant difference was
      observed between groups B and C. CONCLUSIONS: Endoluminal thrombi are very
      frequent in introducers employed for pulmonary artery catheterization but they
      are hardly suspected since the patency of the lumen is usually preserved. The
      lower incidence of thrombosis in groups B and C could hypothetically originate
      from antiaggregant therapy started within 24 hours from the end of surgery for
      myocardial revascularization.

PMID- 10206037
TI  - [The current status of obstetric analgesia and anesthesia in Italy].
AB  - BACKGROUND: There is a more and more vivid interest regarding methods of
      obstetric analgesia and anesthesia while there is a lack of epidemiological data
      about the Italian reality. Aim of the study was to evaluate the current state of
      obstetric analgesia and anesthesia and create an interest for anesthesiologists
      in a professionally and scientifically interesting field. METHODS:  DESIGN:
      transversal study of clinical observation of the Italian situation based on
      questionnaires composed of 20 multiple choice and closed questions, addressed to
      chief anesthesiologists of 220 randomized Italian hospitals. SETTING: 220 Italian
      hospitals having a capacity of more than 100 beds. RESULTS: Out of the 220
      questionnaires, 91 were returned. Merely 17 hospitals guaranteed a permanent
      peridural analgesic service. To improve this situation, anesthesiologists call
      for introducing chargeable services and increasing the medical staff. In spite of
      the widely documented advantages that regional anesthesia offers for maternal and
      fetal well-being, this technique is practised in only 26% of cesarean sections.
      This percentage is greatly higher than that obtained from a similar experience in
      1991, where the use of regional anesthesia technique was of 3-4%. In 11 hospitals
      postoperative analgesia is not carried out on a regular basis. CONCLUSIONS: Even
      though the general opinion is showing a growing interest for obstetric analgesia
      and anesthesia, it has not yet reached the same dignity as in other countries.

PMID- 10206036
TI  - [Acidosis, hypoxia and hypotension in abdominal chemotherapy with blockade of
      arterial and venous circulation (stop flow)].
AB  - BACKGROUND AND AIM: A study was performed of the perioperative systemic effects
      of a recent zoned chemotherapy technique administered in conditions of extreme
      acidosis, hypoxia and modern hypotension. METHODS:  EXPERIMENTAL DESIGN: a
      prospective analysis of the changes compared to basal values using Student's t
      test for paired data. SETTING: Operating theatres and Recovery room. PATIENTS OR
      PARTICIPANTS: A population of 16 consenting patients suffering from abdominal or
      pelvic neoplasms, ASA 1-3, recruited according to the parameters suggested by the
      international literature. SURGERY: central venous catheter, radial arterial
      catheter, open catheter of the e.v. femoral artery, general anesthesia using
      isoflurane. Tests performed: Blood gas analysis of systemic arteries, abdominal
      veins and the superior vena cava at times preceding clamping (T0) and 7 and 14
      mins after the start, at declamping, on reawakening from anesthesia and 30 and 60
      mins afterwards (T1, T2, T3, T4, T5, T6). Serial evaluation of activated
      coagulation time. RESULTS: Mean 25% reduction of neoplastic mass, systemic
      arterial and venous pH diminished at T1 and T2, but more marked and transient at
      T3; district venous pH significantly diminished during entire Stop-Flow. Systemic
      PaO2 increased throughout method (SaO2 > 98%). PaO2 in the superior vena cava
      recorded significantly higher intraoperative values compared to basal and
      postoperative levels, no major differences found at time T3. SaO2 showed
      statistically significant differences between the superior vena cava and the
      abdominal distrist at both T 1 (p 0.0002) and T2 (p 0.004). No toxic effects due
      to NPS were observed. CONCLUSIONS: This is a safe technique but not without
      risks, which requires considerable anesthesiological commitment.

PMID- 10206038
TI  - An investigation of factors contributing to styrene and styrene-7,8-oxide
      exposures in the reinforced-plastics industry.
AB  - During the manufacturing of reinforced plastics, large amounts of styrene and
      trace quantities of styrene-7,8-oxide (SO) are released. Since previous work
      suggests that inhalation of even small amounts of SO might be an important health
      risk, we investigated several possible factors contributing to styrene and SO
      exposure during the manufacture of reinforced plastics. Factors related to job
      type, worker and the type and quantity of styrene-containing resins were
      investigated using mixed-effects multiple linear regression models. Overall, SO
      exposure levels were positively correlated with styrene exposure levels. However,
      this correlation was statistically significant only among hand laminators who had
      the highest exposures to both styrene and SO. An important factor for predicting
      both styrene and SO concentrations was the type of resin used, while the quantity
      of resin consumed was predictive of styrene but not of SO exposure. Since So
      exposure appears to be associated with factors other than coexposure to styrene,
      more effort should be placed on investigating emissions of SO per se. The type of
      mixed-models regression analysis employed in this study can be used for
      clarifying the underlying patterns for exposures to styrene and SO as well as for
      evaluating preventive measures.

PMID- 10206040
TI  - Mineral fibre sampling and size selection.
AB  - Potential health hazards due to fibre inhalation are only evaluated in a limited
      way by simple optical microscopy examination of the membrane filters on which the
      fibres have been collected. One must consider the amount of fibres deposited and
      persisting in the most vulnerable organ compartments. Exposure evaluated in this
      way must take account of the deposition efficiency and relative clearance
      efficiency of different regions of the respiratory tract, which depends mainly on
      the diameter and length distribution of the fibres. The fibre diameter roughly
      indicates the deposition site in the respiratory tract, while the length is
      mainly connected with toxicity. For these reasons, at international level,
      special samplers have been recently proposed, capable of distinguishing the fibre
      sizes, in order to separate the so-called 'thoracic fraction' (the total fibres
      which penetrate beyond the larynx) and the 'respirable fraction' (only the fibres
      reaching the non ciliated respiratory area), which represent the most interesting
      sizes as far as health effects are concerned. Our purpose in this context is to
      explore the feasibility of using the Inertial Spectrometer (INSPEC) as a sampler
      that separates the fibres according to their aerodynamic diameter. The optical
      and electron microscope observations of the samples demonstrate a satisfactory
      size separation of the fibres and alignment along the flow lines. Therefore,
      INSPEC is successful in restricting the microscopic analyses to the potentially
      noxious fibres and in assessing specific concentrations for each diameter
      interval.

PMID- 10206039
TI  - Comparative personal exposures to organic dusts and endotoxin.
AB  - The aims of the study were to provide valid comparative data for personal
      exposures to dust and endotoxins for different occupations and to calculate
      comparative data for the contamination of organic dusts with endotoxin. Nine
      different occupational settings were studied, drawn from the textile,
      agricultural and animal handling industries. Samples were collected by personal
      sampling techniques, using the Institute of Occupational Medicine (IOM) sampling
      head, glass fibre filters and rechargeable sampling pumps. The dust exposures
      were calculated by gravimetric analysis and using the calculated volume of air
      sampled were expressed as mg/m3. Endotoxin exposures were measured using a simple
      water extraction from the collected dusts, followed by a quantitative
      turbidimetric assay. Results were expressed as ng/m3, using the calculated volume
      of air sampled. In addition, the levels of the contamination of dusts with
      endotoxin for individual industries were expressed as ng/mg of collected dust.
      Two hundred and fifty-nine samples, collected from 9 different industries and
      across 36 different sites were analysed. This represented a sampling rate of 25%
      for the total work force. The average sampling time was 4.62 h. For all the dusts
      collected, a significant correlation between the collected dust and endotoxin was
      seen (r = 0.7 and p < 0.001). The highest dust exposures occurred during cleaning
      activities (grain handling: 72.5 mg/m3). The individuals exposed to the highest
      median level of dust and endotoxin were the animal handlers (poultry handlers,
      dust: 11.53 mg/m3, endotoxin: 71,995 ng/m3). Weaving and mushroom cultivation had
      the lowest exposures for dust and endotoxins. The mostly highly contaminated
      dusts (median values expressed as ng of endotoxin per mg of collected dust) were
      found in the animal handling (poultry: 1,030 ng/mg, swine: 152 ng/mg) and cotton
      spinning (522 ng/mg) industries. Processing of cotton and wool fibres was found
      to reduce the levels of contamination of dusts with endotoxin. In the study,
      valid comparative data for personal exposures to organic dusts and endotoxins
      have been presented. The highest exposures were found amongst animal handlers and
      during cleaning activities. The results highlight that dust exposures are greater
      in a number of industries than the set exposure standards. In addition, endotoxin
      exposures are found to be greater than levels at which harmful effects have been
      demonstrated.

PMID- 10206041
TI  - Preliminary external quality assessment for the biological monitoring of carbon
      disulfide with urinary 2-thiothiazolidine-4-carboxylic acid.
AB  - Four laboratories have participated in an external quality control assessment for
      the determination of 2-thiothiazolidine-4-carboxylic acid (TTCA). TTCA is used as
      a biomarker for exposure to CS2. Thirteen different urine samples were analyzed
      by each laboratory. Ten of these were spiked with known amounts of TTCA, and had
      either a high or intermediate creatinine content. Two samples without any TTCA
      were used as controls and one sample was a pool of samples of urine from five
      employees occupationally exposed to CS2. The latter had unknown TTCA content. For
      each sample, TTCA and creatinine concentration were determined. The samples were
      supplied in three consecutive deliveries. Several samples were offered more than
      once. Thus, within-laboratory variability could be established for creatinine and
      TTCA determination and accuracy could be determined for TTCA analysis. Within
      laboratory variability was low for all laboratories for creatinine, although
      laboratory D seemed to have a slight downward bias. Accuracy for TTCA was good
      for all laboratories. No significant mean deviation from the expected TTCA value
      was encountered. There does not seem to be any clear influence of the TTCA
      concentration level of the samples on the accuracy and within-laboratory
      variability. Two of the four laboratories (A and C) showed lower within
      laboratory variability than the other two for TTCA, although coefficients of
      variation between replicated samples are high for these two laboratories as well.
      The laboratory giving the best accuracy, gave the highest within-laboratory
      variability. A non-systematic, random error is probably the source of this. The
      results of this preliminary study indicate that analysis of TTCA, although
      regarded as an established biomarker, can give biases and thus negatively
      interfere with inferred dose-effect or dose-response relationships in
      occupational epidemiology.

PMID- 10206042
TI  - Determination of hydroquinone in air by high performance liquid chromatography.
AB  - A method for measuring hydroquinone in air was evaluated, both in the laboratory
      and in the workplace. The method involved sampling the inhalable fraction onto a
      filter contained in a multi-holed sampler with a back-up of Tenax TA, followed by
      desorption into acetonitrile and analysis by High Performance Liquid
      Chromatography. It was shown to be effective at measuring hydroquinone over the
      range 0.1 to 2 times a concentration of 0.5 mg/m3 for 8 h.

PMID- 10206043
TI  - Multiple miliary osteomas of the face ablated with the erbium: YAG laser.

PMID- 10206044
TI  - Ethical lapses in dermatologic "research".

PMID- 10206045
TI  - Comparison of erbium:YAG and carbon dioxide lasers in resurfacing of facial
      rhytides.
AB  - OBJECTIVE: To compare the efficacy, adverse effects, and histological findings of
      erbium:YAG (Er:YAG) and carbon dioxide (CO2) laser treatment in removing facial
      rhytides. DESIGN: An intervention study of 21 subjects with facial rhytides. All
      participants were followed up for 6 months. The end points of the study were
      wrinkle improvement and duration of adverse effects. SETTING: Academic referral
      center. SUBJECTS: Nineteen female and 2 male volunteers with skin type I to III
      and wrinkle class I to III participated in the study. INTERVENTION: In all
      subjects, 1 side of the face was treated with a CO2 laser and other side with an
      Er:YAG laser. Skin biopsies were performed in 6 subjects before treatment and
      immediately, 1 day, 2 days, and 6 months after treatment. Observations were
      recorded by subjects, investigators, and a blinded panel of experts. MAIN OUTCOME
      MEASURES: Improvement in wrinkles and severity and duration of adverse effects.
      RESULTS: The CO2 laser-treated side had relatively better wrinkle improvement
      when evaluating all subjects (P<.03). However, in subjects receiving more than 5
      passes of Er:YAG laser, improvement scores were not significantly different from
      those for 2 to 3 passes of CO2 laser treatment. Posttreatment erythema was noted
      at 2 weeks in 14 subjects (67%) on the Er:YAG laser-treated side and 20 subjects
      (95%) on the CO2 laser-treated side. The frequency of erythema was significantly
      less after Er:YAG laser treatment at 2 (P=.001) and 8 (P=.03) weeks.
      Hypopigmentation was seen in 1 Er:YAG-treated (5%) and 9 CO2-treated (43%) sides
      (chi2, P<.05). Histological evaluation showed residual thermal damage of up to 50
      microm on the Er:YAG-treated side and up to 200 microm on the CO2-treated side.
      CONCLUSIONS: Erbium:YAG laser is safe and effective in removing facial rhytides.
      Subjects treated with Er:YAG laser recover more quickly from the procedure than
      those receiving CO2 laser treatment.

PMID- 10206047
TI  - Association of the Kobner phenomenon with disease activity and therapeutic
      responsiveness in vitiligo vulgaris.
AB  - OBJECTIVE: To investigate the association between the experimentally induced
      Kobner phenomenon (KP-e) and the Kobner phenomenon by history (KP-h), disease
      activity, and therapeutic responsiveness in vitiligo vulgaris. DESIGN: Cohort
      study. SETTING: An outpatient clinic. PATIENTS: Sixty-one consecutive patients
      with vitiligo vulgaris. INTERVENTION: Three months after a standardized
      epidermodermal injury was induced, the KP-e was evaluated. For 1 year, UV-B (311
      nm) therapy or topical fluticasone propionate plus UV-A therapy was given,
      depending on the severity of depigmentation. MAIN OUTCOME MEASURES: The presence
      or absence of the KP-e and the KP-h disease activity as scored on a 6-point scale
      from -1 to +4 (vitiligo disease activity [VIDA] score) and therapy-induced
      repigmentation grade. RESULTS: Nineteen (31%) of the patients had a positive KP
      h, whereas 37 (61%) showed a positive KP-e (P<.001). The VIDA score did not
      always predict a positive KP-e, although patients with a positive KP-e had a
      higher mean VIDA score (VIDA score of 1.6) than did patients with a negative KP-e
      (VIDA score of 0.5) (P<.001). The responsiveness to UV-B (311 nm) therapy among
      KP-e-positive or KP-e-negative patients was not significantly different (P=.66).
      However, KP-e-positive patients who were treated with fluticasone propionate plus
      UV-A showed a better response than did KP-e-negative patients (P=.01). Among
      patients responding to both therapies, VIDA scores were significantly decreased
      (P<.001) compared with VIDA scores before therapy. CONCLUSION: The KP-e may
      function well as a clinical factor to assess present disease activity and may
      also predict the responsiveness to fluticasone propionate plus UV-A therapy but
      not to UV-B (311 nm) therapy.

PMID- 10206046
TI  - Urinary porphyrin excretion in a human population highly exposed to
      hexachlorobenzene.
AB  - BACKGROUND: Data from an epidemic reported in Turkey (1955-1959) is the only
      information about the relationship between hexachlorobenzene (HCB) intake and
      porphyria cutanea tarda in humans. No information is available on the HCB
      threshold exposure level to induce porphyria cutanea tarda. OBJECTIVES: To study
      HCB serum levels and urinary porphyrin excretion in the inhabitants of a village
      located near an organochlorine compound factory with high HCB concentrations in
      the air and to detect possible alterations in urinary porphyrin excretion and
      examine their relationship with HCB serum levels. DESIGN: Cross-sectional study.
      SETTING: Unit of Porphyrias of a tertiary care facility in Barcelona, Spain.
      PARTICIPANTS: Six hundred four inhabitants of the village who were older than 14
      years provided serum and urine samples (185 participants were factory workers).
      MAIN OUTCOME MEASURES: Serum HCB was analyzed by gas chromatography coupled to
      electron capture detection. Quantification of urinary total porphyrins was
      performed by spectrofluorimetry. Porphyrin profile was determined by high
      pressure liquid chromatography. RESULTS: Hexachlorobenzene was detected in all
      serum samples (mean, 39.8 ng/mL; range, 1.1-1616.0 ng/mL), and levels were higher
      in factory workers. Mean +/- SD level urinary total porphyrin average
      concentration was 98 +/- 69 nmol/L (range, 9-1009 nmol/L). Only the urine sample
      with the highest porphyrin concentration showed an increase of highly
      carboxylated porphyrins, with a typical profile of porphyria cutanea tarda. In
      the remaining 603 urine samples, coproporphyrin was the predominant fraction.
      CONCLUSION: The airborne exposure to and increased body burden of HCB in the Flix
      village population are not enough to trigger a significant alteration of the heme
      biosynthesis pathway.

PMID- 10206048
TI  - Vitiligo antibodies are not directed to tyrosinase.
AB  - BACKGROUND: Patients with vitiligo have a markedly increased incidence of
      antibodies to melanocytes, referred to as vitiligo antibodies. Antibodies to
      tyrosinase have been reported in some patients with vitiligo, suggesting that
      vitiligo antibodies may be directed to this enzyme. However, there is
      considerable controversy as to the frequency with which these antibodies occur,
      and, hence, about their relevance to the pathogenesis of vitiligo. The frequency
      with which antityrosinase antibodies occur in vitiligo is critical to evaluate
      their potential role in the pathogenesis of this disease. OBJECTIVE: To examine
      the prevalence of antibodies to tyrosinase in a large group of patients with
      vitiligo. DESIGN: We examined the incidence of antibodies to enzymatically and
      immunologically active tyrosinase in patients with and without vitiligo. SETTING:
      Outpatient clinic in referral center. PATIENTS: The study was conducted on serum
      samples obtained from 54 patients with active (n = 40) and inactive (n = 14)
      uncomplicated vitiligo and from 52 age- and sex-matched individuals without
      vitiligo. MAIN OUTCOME MEASURE: Presence in the serum of antibodies to
      enzymatically and/or immunologically active tyrosinase. RESULTS: By
      immunoblotting, 20 patients (50%) with active vitiligo, 9 of those (64.3%) with
      inactive vitiligo, and 29 control individuals (55.8%) had antibodies to an
      antigen that comigrated with tyrosinase. However, by immunoprecipitation DOPA
      stain and by sandwich enzyme-linked immunosorbent assay, none of the vitiligo or
      control individuals had antibodies to tyrosinase, even though both assays easily
      detected control antityrosinase antibodies. CONCLUSION: These results indicate
      that while antibodies to an antigen(s) that comigrates with tyrosinase are common
      in patients with or without vitiligo, vitiligo antibodies are not directed to
      tyrosinase.

PMID- 10206049
TI  - Efficacy of erbium:YAG laser ablation in Darier disease and Hailey-Hailey
      disease.
AB  - BACKGROUND: Among different surgical approaches, dermabrasion and carbon dioxide
      laser vaporization have been used to treat Hailey-Hailey disease (HHD) (familial
      benign chronic pemphigus) and Darier disease (DD) (keratosis follicularis), with
      various results. Because of the erbium: YAG laser's unique absorption
      characteristics in tissue water, erbium:YAG laser ablation combines the
      advantages of both techniques, avoiding thermal injury of vaporization and also
      allowing selectively deeper tissue removal in the follicular lesions of DD.
      Therefore, good results should be expected in both types of acantholytic
      disorders. OBSERVATIONS: Four patients (2 with HHD and 2 with DD) with different
      affected areas were treated with laser ablation. During a follow-up period
      ranging from 8 to 20 months, complete remission was achieved in 3 patients--2
      with DD and 1 with HHD--and significant improvement was achieved in 1 patient
      with HHD. Histological examination of control biopsy specimens after ablation in
      1 patient with DD revealed no signs of the disease and only a slight fibrosis in
      the papillary dermis. CONCLUSIONS: Erbium:YAG laser ablation effectively removes
      lesions of both HHD and DD and can also yield excellent long-term results in
      chronic, recalcitrant cases.

PMID- 10206050
TI  - Pulse dosing of thioguanine in recalcitrant psoriasis.
AB  - BACKGROUND: Patients with severe psoriasis may be unresponsive to or unable to
      tolerate the adverse effects of traditional therapy. Thioguanine has been used to
      treat psoriasis, but experience is limited. Most previous studies have used daily
      therapy and have demonstrated significant hematologic abnormalities. OBJECTIVE:
      To reduce the adverse effects of traditional thioguanine therapy, our study
      patients were treated with thioguanine with a pulse-dosing schedule of 2 to 3
      times per week. OBSERVATIONS: Marked improvement of recalcitrant psoriasis was
      noted in 10 (71%) of 14 patients receiving thioguanine therapy using a pulse
      dosing schedule. Maintenance dosage ranged from 120 mg twice a week to 160 mg 3
      times a week. Adverse effects were minimal. CONCLUSIONS: Thioguanine therapy is
      an effective treatment for recalcitrant psoriasis. A dosing schedule of 2 or 3
      times per week is recommended to minimize the potential adverse effects. Routine
      laboratory follow-up is suggested to screen for potential adverse effects, with
      special attention to bone marrow suppression.

PMID- 10206051
TI  - Oral Crohn disease: clinical characteristics and long-term follow-up of 9 cases.
AB  - BACKGROUND: Oral localization of Crohn disease is uncommon and must be
      differentiated from nonspecific lesions. Its natural course and its long-term
      prognosis are unknown. OBSERVATIONS: We studied 9 patients (8 male, 1 female; age
      range, 7-52 years; median age, 16 years) with Crohn disease and specific oral
      lesions, including deep linear ulcers, pseudopolyps, and/or labial or buccal
      swelling and induration. The prevalence of such lesions was 0.5%. The median
      follow-up was 11 years. Oral localization developed before (n = 2), at the same
      time as (n = 2), or after (n = 5) the onset of the digestive disease. Noticeable
      associated localizations were observed in the anoperineum (n = 8) and the
      esophagus (n = 3). The median duration of the oral lesions was 4 years (range, 1
      13 years), without necessary parallelism with the digestive localization. Five
      patients had complete healing after a median delay of 2 years. CONCLUSIONS: Oral
      localization of Crohn disease is characterized by a marked male predominance, a
      young age at onset of Crohn disease, and a very protracted course. The high
      prevalence of associated anal and esophageal involvement suggests that Crohn
      lesions have a particular trophicity for squamous cell epithelium.

PMID- 10206052
TI  - Why does carbon dioxide resurfacing work? A review.
AB  - Despite the unquestionable efficacy of carbon dioxide laser skin resurfacing,
      mechanisms for cosmetic enhancement remain poorly characterized. Histological
      studies have provided some insight into the cascade of events from initial laser
      impact to final skin rejuvenation. However, there are few comprehensive studies
      of gross and microscopic wound healing. Additionally, the literature is
      fragmented; excellent individual articles appear in journals from widely
      disparate disciplines. For example, some reports relevant to laser skin
      resurfacing are "sequestered" in the engineering literature. This article is
      intended to update the physician on laser skin resurfacing based on the broadest
      review of the current literature. It proceeds from a discussion of initial laser
      tissue interactions, such as collagen denaturation, to examination of long-term
      biological sequelae. At some cost to scientific rigor, mathematical models
      describing laser-tissue interactions are not presented.

PMID- 10206053
TI  - Medical ethics relating to clinical investigations using human subjects.

PMID- 10206054
TI  - Hexachlorobenzene and porphyria cutanea tarda.

PMID- 10206055
TI  - A solitary tumor of the left temple.

PMID- 10206056
TI  - Hypopigmented papules of the cheeks, neck, and shoulders.

PMID- 10206057
TI  - Persistent pruritic plaque of the ear.

PMID- 10206058
TI  - Asymptomatic nasal mass.

PMID- 10206059
TI  - Ethics, the prison system, and dermatology.

PMID- 10206060
TI  - Chronic actinic dermatitis is not a viable concept.

PMID- 10206061
TI  - The changing spectrum of the cutaneous manifestation of HIV disease.

PMID- 10206062
TI  - Follow-up letter from Tanzania.

PMID- 10206063
TI  - Textural change following treatment of facial telangiectasias with the tunable
      pulsed-dye laser.

PMID- 10206064
TI  - The importance of early Cushing disease diagnosis.

PMID- 10206065
TI  - Comparison of calcipotriene (Dovonex) with a coal tar emulsion (Exorex) in
      treating psoriasis in adults: a pilot study.

PMID- 10206066
TI  - Extracorporeal photochemotherapy for the treatment of erythrodermic pityriasis
      rubra pilaris.

PMID- 10206067
TI  - Applying the Nottingham Prognostic Index to a Swedish breast cancer population.
      South East Swedish Breast Cancer Study Group.
AB  - The aim of this study was to assess the applicability of histopathological
      grading according to the protocol of Elston/Ellis and the Nottingham Prognostic
      Index (NPI) to a defined breast cancer population. The NPI is the sum of the
      individual scores concerning grade, tumour size, and lymph node status, each
      weighted according to regression coefficients of a Cox proportional hazard
      analysis and calculated for each individual breast cancer patient. 630
      consecutive patients with invasive breast cancer diagnosed 1988-91 were
      retrospectively followed up and their tumours reviewed and graded. A Cox
      proportional hazard analysis was performed. Grade, lymph node status, and tumour
      size were statistically significant predictors of survival within the follow up
      period (median 7.2 years). Similar to NPI, a temporary index (Kalmar Prognostic
      Index, KPI) was derived and normalised to NPI for comparison (KPI(norm)). NPI and
      KPI(norm) gave similar prognostic power in spite of the differences of the
      patient populations from which the 2 indices were derived. Patients with NPI 4 or
      less had 0.66% breast cancer specific mortality during the follow up time. 14% of
      the patients with NPI 4.1-5 and 32% of those with an index sum 5.1-6 died from
      breast cancer during this time. Younger patients tended to have higher grade
      tumours. We advocate the common use of grade and the NPI in order to increase the
      comparability of groups of patients receiving different therapies.

PMID- 10206068
TI  - Loss of heterozygosity in BRCA1 and BRCA2 markers and high-grade malignancy in
      breast cancer.
AB  - Loss of heterozygosity (LOH) in loci of the 17q21 and 13q12-13 regions can
      collaborate in the inactivation of BRCA1, BRCA2, and possibly other genes
      implicated in the pathogenesis of breast carcinomas. We investigate allelic
      losses in microsatellites of the BRCA1 and BRCA2 regions, and their correlations
      with seven pathologic parameters in 140 breast carcinomas. Those cases showing
      LOH in the region of the RB gene, 13q14, were excluded from the study. The LOH
      analysis was performed by amplifying DNA by PCR, using four markers of the 17q21
      region (D17S856, D17S855, D17S1323, and D17S1327) and four markers of the 13q12
      13 region (D13S290, D13S260, D13S310, and D13S267). LOH in the BRCA1 region was
      found in 47% of tumors, correlating significantly with estrogen receptor content
      (p = 0.025), progesterone receptors (p = 0.004), higher grade (p = 0.0008),
      peritumoral vessel invasion (p = 0.001), and lymph node metastases (p = 0.002).
      When we excluded the cases with LOH in the BRCA2 region and those not informative
      for it, the significance disappeared. In the BRCA2 region, a rate of LOH of 51%
      was found; it correlated significantly with estrogen receptor content (p =
      0.002), progesterone receptors (p = 0.03), peritumoral vessel invasion (p =
      0.005), higher grade (p = 0.002), and lymph node metastases (p = 0.001). When
      cases with BRCA1 losses and those not informative were excluded, again the
      significance disappeared. Concomitant losses in the BRCA1 and BRCA2 regions were
      found in 32% of cases, correlating significantly with lymph node metastases (p =
      0.0002), estrogen receptor content (p = 0.003), progesterone receptors (p =
      0.001), histologic grade (p = 0.01), and peritumoral vessel invasion (p =
      0.0004). These results suggest that concomitant losses in both regions could have
      a functional effect, influencing the presence of a poor tumor pathophenotype in
      breast carcinomas.

PMID- 10206069
TI  - The methodology of quantitation of microvessel density and prognostic value of
      neovascularization associated with long-term survival in Japanese patients with
      breast cancer.
AB  - The present study updates results on methodology of quantitation of tumor
      neovascularization and those on the prognostic value of microvessel density (MVD)
      in breast cancer tissue previously published in the World J. Surg. 21: 49-56,
      1997. The follow-up period of observation of the series was extended to 20 years,
      and new biological indicators (i.e., proliferating cell nuclear antigen (PCNA), c
      erbB-2, and p53) were included in the analysis. There were 109 patients with
      primary breast cancer, from 1971 to 1979, followed up for a median of 14 years
      (range, 1-20). A representative median longitudinal section of each breast tumor
      was immunohistochemically stained with factor VIII-related antigen and analyzed.
      The three methods of identifying MVD were: (1) average microvessel count
      (AMC)/mm2, (2) central microvessel count (CMC)/mm2, and (3) highest microvessel
      count (HMC)/mm2. Thirty-one patients (28.4%) died of breast cancer. There was a
      relationship between MVD and peritumor blood vessel invasion (AMC: p = 0.0114,
      CMC: p = 0.0319, and HMC: p = 0.0009). However, there was no relationship between
      MVD and other factors. Univariate analysis showed that node status (p < 0.0001),
      histological grade (p < 0.0001), clinical tumor size (T) (p = 0.0002), PCNA (p =
      0.0033), p53 (p = 0.0043), mitotic grade (p = 0.0092), AMC (p = 0.0214), and
      peritumor lymphatic vessel invasion (p = 0.0467) were significantly predictive of
      overall survival. HMC was borderline significant (p = 0.0702), while CMC and c
      erbB-2 were not significant. Multivariate analysis showed that T (p = 0.0005),
      node status (p = 0.0053), and AMC (p = 0.0485) were independent factors, but
      neither CMC nor HMC was independent. AMC, a significant independent prognostic
      factor, might be a better method than the others for evaluating angiogenesis, but
      further and larger studies are warranted.

PMID- 10206070
TI  - Analyses of microsatellite instability and the transforming growth factor-beta
      receptor type II gene mutation in sporadic breast cancer and their correlation
      with clinicopathological features.
AB  - To determine the incidence of microsatellite instability (MSI) and its
      relationship with both clinicopathologic parameters and patient survival, 101
      cases of breast cancer were investigated. In addition, transforming growth factor
      beta (TGF-beta) receptor type II (RII) gene mutation was also examined to clarify
      the relation to MSI in breast cancer development. MSI and RII gene mutation were
      screened by single strand conformation polymorphism (SSCP). The mutations of the
      RII gene were confirmed by a direct sequence. An association between the MSI
      status and the clinicopathological features was examined to assess the potential
      of the MSI status as a prognostic indicator in sporadic breast cancer cases. MSI
      was detected in 12 of 101 (11.9%) breast cancer cases. The positive MSI breast
      cancer cases showed relatively more advanced disease than negative MSI cases, and
      also exhibited relatively poorer prognoses. No RII gene mutations were observed
      in any of the breast cancer cases. Our data suggest that the MSI status may thus
      be a useful indicator for the prognosis of sporadic breast cancer cases. However,
      the breast seems to be an infrequent target organ for cancer development through
      RII gene mutations. As a result, tumor progression through this pathway appears
      to be related to organ specificity. For positive MSI breast cancers, other target
      genes therefore still need to be identified.

PMID- 10206071
TI  - Antisense oligonucleotides to the epidermal growth factor receptor.
AB  - Overexpression of the epidermal growth factor receptor (EGFR) has been observed
      in human breast tumors and is associated with poor prognosis in breast cancer
      patients. This would suggest that blocking the activity of the EGFR is a logical
      approach in the treatment of breast cancer. Three 20-mer phosphorothioate
      oligodeoxynucleotides were designed to target different regions of the human
      epidermal growth factor receptor (EGFR) mRNA. Several analogs of these
      oligodeoxynucleotides (the 2'-fluoro analog, the 2'-propoxy analog, and/or the 5
      methyl cytosine analog) were also evaluated. We added these compounds to a human
      ovarian carcinoma cell line (SKOV3) and a human lung carcinoma line (A549), both
      of which overexpress the EGFR. All of these antisense oligonucleotides inhibited
      expression of the 10 kb EGFR mRNA (range: 22-97% inhibition) compared to a
      scrambled control oligonucleotide or an untreated control. Expression of the less
      prominent 5.6 kb EGFR mRNA band was also inhibited by all but two of the parent
      oligonucleotides. No inhibition of this 5.6 kb band was found with the control
      oligonucleotide. The reduction in the expression of EGFR mRNA by the three most
      potent antisense compounds was accompanied by a significant reduction of EGFR
      protein (90-98%) and in vitro growth inhibition of SKOV3 cells as compared to the
      control oligonucleotide.

PMID- 10206072
TI  - Quantitative changes in cytological molecular markers during primary medical
      treatment of breast cancer: a pilot study.
AB  - AIM: To quantify the changes in biological molecular markers during primary
      medical treatment in patients with operable breast cancer and to assess their
      possible relationship with response to treatment. METHODS: The treatment group
      consisted of 31 patients with operable breast carcinomas, median age 57 years
      (range 41-67), treated with four 3-weekly cycles of chemotherapy with
      Mitoxantrone, methotrexate (+/- mitomycin C), and tamoxifen before surgery. Fine
      needle aspiration (FNA) was used to obtain samples from patients prior to and at
      10 or 21 days post-treatment. The following molecular markers were assessed:
      estrogen receptor (ER), progesterone receptor (PgR), p53, Bcl-2, and Ki67
      measured by immunocytochemistry, and ploidy and S-phase fraction (SPF) by flow
      cytometry. To evaluate the reproducibility of the technique, repeat FNA was
      performed in a separate non-treatment control group of 20 patients and the same
      molecular markers assessed, two weeks after the first sample with no intervening
      treatment. RESULTS: The non-treatment control group showed a high reproducibility
      for the measurement of molecular markers from repeat FNA. In the treatment group
      there was a non-significant reduction in SPF and a significant reduction (p =
      0.005) in Ki67. Patients who responded to neoadjuvant therapy were more likely to
      have a reduction in these two markers than those who failed to respond.
      Similarly, a reduction in ER scores was observed between the first and second
      samples (p = 0.04). For PgR, the change between the first and second samples was
      not significant although there was a significant difference between responders
      and non-responders (p = 0.03). All nine patients with an increase in PgR were
      responders. No significant changes in p53 or Bcl-2 were observed during
      treatment. CONCLUSION: Molecular markers can be adequately measured from FNA
      samples prior to and during neoadjuvant therapy. Changes in cellular
      proliferation and hormone receptors have been shown that may be related to tumour
      response. These relationships should be assessed in a larger cohort of patients.

PMID- 10206074
TI  - Development of a knowledge scale about breast cancer and heredity (BCHK).
AB  - An 11-item questionnaire, the Breast Cancer and Heredity Knowledge Scale (BCHK),
      was developed to test general knowledge about breast cancer and hereditary breast
      cancer (HBC) among women at low to moderate risk of HBC. The BCHK measures
      knowledge about breast cancer incidence and prognosis, risk factors, screening,
      disease presentation and treatment, and HBC. Scale items were generated from
      focus group interviews, previously published breast cancer knowledge scales, and
      consultation with a multidisciplinary research team, including health
      professionals and women with breast cancer or a family history of breast cancer.
      A 27-item draft scale was tested on 36 breast clinic patients and 17 women from
      the general public. Results were used to develop the final 11-item scale.
      Development of the scale and its potential uses are discussed.

PMID- 10206073
TI  - p53 expression in breast and endometrium during estrogen and tamoxifen treatment
      of surgically postmenopausal cynomolgus macaques.
AB  - Estrogens are important for both normal cell growth and malignant proliferation
      in the mammary gland as well as in the endometrium. Tamoxifen is a non-steroidal
      anti-estrogen widely used in breast cancer treatment. In recent years reports
      have been made of an increased risk of endometrial carcinoma during tamoxifen
      treatment. We used surgically menopausal cynomolgus macaques to study
      proliferation and p53 expression during hormonal replacement therapy (HRT) and
      tamoxifen treatment. Animals were treated continuously for 35 months with either
      conjugated equine estrogens (CEE; n = 20); medroxyprogesterone acetate (MPA; n =
      17); the combination of CEE + MPA (n = 13); or tamoxifen (n = 17) for 35 months.
      We found an increased expression of p53 in normal breast and endometrial tissue
      linked to CEE but not tamoxifen treatment. In the breast alveoli there was an
      association between proliferation measured by morphometry and p53 expression in
      all groups. However, in the endometrium CEE induced significantly more p53
      positivity than tamoxifen, 9/20 vs. 3/17 in glands and 9/19 vs. 0/17 in stroma,
      respectively. If indeed long-term treatment with tamoxifen as in the present
      study could inactivate the tumor-suppressive function of p53, endometrial cells
      might thereby become more susceptible to genetic lesions associated with
      carcinogenesis.

PMID- 10206075
TI  - Predictive chemotherapy of advanced breast cancer directed by MTT assay in vitro.
AB  - In order to investigate the predictive value of in vitro MTT assay for directing
      chemotherapy of breast cancer patients, from 1992 to 1995, 156 advanced breast
      cancer patients who had evaluable lesions were recruited for a prospective study.
      Of them 83 had MTT assay before chemotherapy; the 73 patients in the MTT
      sensitive group received chemotherapy according to the result of the MTT assay.
      The other 10 patients in the MTT resistant group and 73 patients in the control
      group were given chemotherapy according to clinicians' discretion. The response
      rate in the MTT sensitive group was 76.7% (56/73). There was statistically
      significant difference as compared with 0 (0/10) in the MTT resistant group and
      43.8% (32/73) in the control group. Between in vitro and in vivo, the overall
      coincident rate was 79.5% [(56 + 10)/83]. In the MTT sensitive group, the
      response rate of the subgroups of lesions and the chemotherapy regiments tended
      to be higher than that in the control group. Patients in the MTT sensitive group
      had longer response and survival than those in the control group. However, there
      was no statistical difference in the median response duration and the median
      survival between the two groups. Further exploration of in vitro chemosensitivity
      testing by MTT assay for patients with advanced breast cancer is warranted.

PMID- 10206076
TI  - Male breast cancer in the hereditary nonpolyposis colorectal cancer syndrome.
AB  - A male member of a large HNPCC kindred, affected by primary malignancies of the
      breast and colon, was identified. This individual was found to harbor a germline
      mutation of the MLH1 mismatch repair gene previously shown to segregate with
      disease in this kindred. The breast tumor exhibited somatic reduction to
      homozygosity for the MLH1 mutation, and microsatellite instability was evident in
      the breast tumor. We conclude that hereditary male breast cancer can occur as an
      integral tumor in the HNPCC syndrome.

PMID- 10206077
TI  - Meta-analytic review of the clinical effectiveness of oral deferiprone (L1).
AB  - OBJECTIVE: To summarize efficacy and effectiveness in iron overloaded patients
      treated with the orally active iron chelator deferiprone also known as L1 or,
      using meta-analysis of the literature. METHODS: We reviewed the literature,
      searching Medline and Embase databases, as well as reviews and other literature
      on the topic. Inclusion criteria were: original clinical trials reporting results
      for serum ferritin concentration (SF), hepatic iron concentration or urinary iron
      excretion (UIE). Efficacy data had to have been reported after > or =3 months of
      treatment. Data were combined using a random effects model (Cochrane) modified
      for use with single groups to produce a point estimate and a 95% confidence
      interval. To summarize the clinical effectiveness, overall proportion of patients
      where deferiprone was able to reduce serum ferritin was calculated. We also
      examined average (mg x l(-1)) serum ferritin levels over the reported time (mean)
      and absolute decrease from the baseline after therapy. To summarize efficacy,
      success was defined as the proportion of patients who achieved UIE of 25 mg per
      day or 0.5 mg x kg(-1) x day(-1), which equals the average amount received from
      monthly blood transfusions. We also calculated the overall average level (mg per
      day) of UIE over the reported time of therapy (mean). As part of a sensitivity
      analysis, data were analyzed for two ranges of deferiprone dosage: < or = 50 mg x
      kg(-1) x day(-1) and > or =75 mg x kg(-1) x day(-1). RESULTS: Of 83 identified
      references, nine clinical trials met our inclusion criteria, providing data for
      129 iron overloaded patients. After a mean of 16 months of therapy (range 6.4 36
      months) with 66.4 mg x kg(-1) x day(-1) (mean) of deferiprone, 75.5% of highly
      iron overloaded patients had a decrease in serum ferritin from baseline. The
      average drop in serum ferritin of 0.8 mg x l(-1) was 23.5% from baseline. The
      overall average UIE for therapy was 28.8 mg per day in patients receiving > or =
      75 mg x kg(-1) x day(-1) over 8.5 months of therapy. At the same dosage, more
      than half of the patients (51.8%) achieved negative iron balance. When studies
      with patients receiving lower dosage (< or = 50 mg x k(-1) x day(-1)) were
      included, the success rate was 45.1%. CONCLUSION: Overall, deferiprone has
      clinical efficacy in achieving negative iron balance and reducing body iron
      burden in highly iron overloaded patients. After an average of 16 months of
      deferiprone in doses > or = 75 mg x kg(-1) x day(-1), most patients had a
      decrease in ferritine concentration.

PMID- 10206078
TI  - Nasal decongestion with imidazoline derivatives: acoustic rhinometry
      measurements.
AB  - OBJECTIVE: The objective of this single-blind study was to establish whether
      there are any differences between conventional imidazoline-containing nasal drops
      with regard to duration of action and decongestion potential. METHODS: Six
      different substances were each administered to 108 healthy volunteers (nine
      groups of 12 adults), respectively, in the concentration recommended for adults
      (and two also in that recommended for infants) over a period of 8 h in comparison
      with 0.9% NaCl. The volumetric measurement of the nasal lumen was conducted by
      means of acoustic rhinometry (Rhinoklack). RESULTS: The decongestive effect of
      all imidazoline preparations set in relatively uniformly, without any appreciable
      differences. After 20 min all the products exhibited approximately 60% of their
      maximum decongestive effect, which was achieved after approximately 40 min,
      having produced an increase in volume of approximately 20%. In contrast, in terms
      of duration of action, considerable differences between the individual products
      were to be discerned: indanazoline 0.118%, naphazoline 0.02% and tetryzoline 0.1%
      had no effect whatsoever after 4 h. Oxymetazoline 0.05% and 0.01%, xylometazoline
      0.025% and 0.1%, and tramazoline 0.1264% still had an appreciable effect after 4
      h, while after 8 h only oxymetazoline 0.05% and 0.01% still had a relevant
      decongestive effect. A rebound effect associated with reactive hyperaemia was
      observed after 8 h in all short-acting products (indanazoline, naphazoline,
      tetryzoline and tramazoline), which in the case of indanazoline was even
      associated with a reduction in the nasal lumen. Interestingly, there were no
      differences between the xylometazoline and oxymetazoline concentrations
      recommended for adults and those for infants in terms of efficacy. The low-dose
      concentrations of the preparations for infants appear to be sufficient to produce
      a satisfactory therapeutic effect.

PMID- 10206079
TI  - Laboratory data in healthy volunteers: reference values, reference changes,
      screening and laboratory adverse event limits in Phase I clinical trials.
AB  - OBJECTIVE: Laboratory data are key evaluation procedures for Phase I clinical
      pharmacology for two reasons. Firstly, laboratory data are used within the
      screening process to exclude subjects with asymptomatic diseases, which could
      result in increased danger to themselves or confuse interpretation of the study
      results. Secondly, during study implementation, safety evaluation and in
      particular maximum tolerated dose determination have to be done by a case-by-case
      analysis, sometimes using laboratory adverse events (LAEs). Thus, relevant limits
      are needed to discriminate between a usual common variation and a significant
      abnormality, which is considered to be a LAE. This report presents laboratory
      data distribution, reference values and reference changes and, based on
      previously published new methods, suggests inclusion limits at screening and
      laboratory adverse event limits for analysis during study implementation.
      SUBJECTS AND METHODS: Nine hundred and twenty-seven young healthy male volunteers
      were recruited in one centre (Association de Recherche Therapeutique). A standard
      screening process was carried out. Protocols were approved by the local ethics
      committee. Blood sampling was performed in the same conditions. Reference values
      (at screening and at baseline) were determined by a non-parametric procedure
      selecting 2.5% and 97.5% of the distribution of data. Reference changes were also
      defined as the 2.5-97.5% interval of distribution of the variations between the
      end of treatment and baseline. Inclusion limit and LAE limit methods of
      determination used had been specified in previous articles. RESULTS: Detailed
      results of laboratory data distribution, reference values at screening and at
      baseline, reference changes, inclusion limits and LAE limits are presented in
      tables with number of subjects, mean, median, standard deviation, minimal and
      maximal values and the 2.5-97.5% interval for each laboratory parameter.
      CONCLUSION: The key aims of this paper are to provide clinical pharmacologists
      with data, reference values or changes obtained in the real conditions of Phase I
      study implementation, and to propose relevant limits, either for screening as
      inclusion limits, or during studies as LAE limits. Thus, these data, reference
      values and specific limits improve the capacity to screen healthy volunteers and
      to analyse LAEs during Phase I studies.

PMID- 10206080
TI  - CYP2D6 polymorphism in systemic lupus erythematosus patients.
AB  - OBJECTIVES: To determine whether patients with idiopathic systemic lupus
      erythematosus (SLE) are associated with impaired CYP2D6 activity and to gain
      insight into whether there is an association between particular CYP2D6 genotypes
      and susceptibility to SLE, and whether CYP2D6 polymorphism is linked to any
      specific clinical features of SLE. METHODS: Debrisoquine sulfate (10 mg p.o.) was
      given to 159 healthy volunteers and 39 idiopathic SLE patients. Genotypic assay
      was carried out in 80 healthy volunteers and 32 patients. A 10-ml blood sample
      was drawn for genotypic assay. Debrisoquine and 4-hydroxydebrisoquine were
      determined in 8-h urine samples. Blood samples were analysed for the presence of
      mutations in the CYP2D6 gene, by using polymerase chain reaction (PCR) specific
      for CYP2D6*3 and CYP2D6*4 alleles. RESULTS: The metabolic ratio of debrisoquine
      to 4-hydroxydebrisoquine ranged from 0.01 to 86.98 in healthy subjects and from
      0.02 to 96 in SLE patients. We observed the poor metabolizer(PM) debrisoquine
      phenotype in three of 39 patients with idiopathic SLE (7.6%) and five of 159
      healthy subjects (3.1%). There was no significant difference in the frequency of
      PM phenotypes between idiopathic SLE and healthy subjects (Fisher's exact test, P
      = 0.19). No significant difference in the distribution of overall genotypes and
      allele frequencies were observed between the two groups. No significant
      relationships were found between specific clinical features and the overall
      genotype. CONCLUSION: The results of this study confirm that CYP2D6 activity is
      not impaired in SLE and that there is no association between SLE and phenotypic
      CYP2D6 status. The results also showed that there was no difference in the
      frequency of CYP2D6A and CYP2D6B alleles between controls and patients with SLE.

PMID- 10206081
TI  - A double-blind study of MPV-2213ad, a novel aromatase inhibitor, in healthy male
      subjects.
AB  - OBJECTIVE: Novel aromatase inhibitors are developed with requirements of high
      potency and selectivity for the aromatase enzyme. The hormonal effects of a new,
      non-steroidal competitive inhibitor of the aromatase enzyme, MPV-2213ad, were
      investigated in this study. METHODS: The study was conducted as a double-blind,
      placebo controlled phase I study, where 32 healthy male volunteers were
      randomized to receive a single oral dose of either 0.3, 3 or 100 mg of MPV-2213ad
      or placebo. Serum concentrations of estradiol (E2), testosterone, follicle
      stimulating hormone (FSH), luteinizing hormone (LH), cortisol and aldosterone
      were determined from samples taken 0, 4, 8 h and 12 h during the day of drug
      administration and 1, 2, 4 and 7 days after drug intake. The individual diurnal
      variation of circulating hormone concentrations was determined in all
      participants at 0, 4, 8 h and 12 h on the day before drug intake. Specimens for
      hematological and biochemical analyses were also collected. RESULTS: A dose
      dependent and statistically significant (P < 0.001) decrease in serum E2
      concentrations was induced by MPV-2213ad. Lowest mean values were observed 8-12 h
      after drug administration and at 24 h the reductions were 10%, 34% and 69% from
      baseline in the 0.3-mg, 3-mg and 100-mg groups, compared with an 18% increase in
      the placebo group. Serum E2 concentrations returned to baseline within 4 days in
      all study subjects. A significant increase was observed in the serum
      concentrations of testosterone (P = 0.016), LH (P = 0.002) and FSH (P < 0.001)
      after administration of MPV-2213ad. Serum concentrations of cortisol and
      aldosterone were unaffected by MPV-2213ad. The drug was well tolerated.
      CONCLUSION: Single oral doses of MPV-2213ad, given to healthy male subjects,
      induced hormonal effects typical for a specific and selective inhibitor of the
      aromatase enzyme. Importantly, this study design with the determination of the
      diurnal rhythm in the levels of the corresponding hormones gives additional
      validity on the results.

PMID- 10206082
TI  - Effects of general anaesthetic procedures on mitochondrial function of human
      skeletal muscle.
AB  - BACKGROUND: General anaesthetics inhibit mitochondrial function in animal models.
      However, very few studies have been performed in humans, and the results have not
      been conclusive. METHODS: We prospectively studied the oxygen consumption and the
      individual enzyme activity of each complex of the mitochondrial respiratory chain
      of skeletal muscle mitochondria in 54 healthy individuals who underwent general
      anaesthesia for orthopaedic surgery. The control group (n = 54) was made up of
      individuals submitted to the same orthopaedic procedure under regional
      anaesthesia (n = 31), and patients who underwent muscle biopsies for diagnostic
      purposes by local anaesthesia (n = 23). RESULTS: We found a significant decrease
      in the oxidation of glutamate (-36%), succinate (-25%) and ascorbate (-29%) in
      the general anaesthetic group compared with the controls (P < 0.001 for all
      substrates). The level of such inhibition was similar for volatile anaesthetics
      with strong (halothane) or weak (isoflurane) negative inotropic effect. By
      contrast, the enzymatic activity of all individual complexes and the coupling of
      oxidative phosphorylation did not differ between the two groups. CONCLUSION: We
      conclude that during general anaesthetic procedures there is an extensive
      inhibition of substrate oxidation in human muscle mitochondria, and that it is
      not caused by a direct effect on complexes of the mitochondrial respiratory chain
      or through uncoupling oxidative phosphorylation.

PMID- 10206083
TI  - CYP2C19 genotypes and omeprazole metabolism after single and repeated dosing when
      combined with clarithromycin.
AB  - OBJECTIVES: Omeprazole is metabolized mainly by CYP2C19 which has two major
      mutations (CYP2C19*2 in exon5 and CYP2C19*3 in exon4) associated with the poor
      metabolizer (PM) phenotype. The aim of this study was to examine the relationship
      between genetic polymorphism of CYP2C19 and metabolism of omeprazole
      administrated as a single dose or as repeated-doses, which were in both cases co
      administered with clarithromycin. METHODS: Twelve healthy Japanese subjects were
      typed for CYP2C19 polymorphism. In the single-dose study, plasma levels of
      omeprazole and its metabolites were measured for 24 h after administration of 20
      mg omeprazole and 400 mg clarithromycin to six healthy Japanese subjects. In the
      repeated-dose study, plasma levels of omeprazole and its metabolites were
      measured after repeated oral administration of 20 mg omeprazole and 400 mg
      clarithromycin twice daily for 6 days and then after 20 mg omeprazole and 400 mg
      clarithromycin once on the 7th day to the other 6 healthy Japanese subjects.
      RESULTS: In the single-dose study, the areas under the plasma concentration
      versus-time curve (AUCs) of omeprazole of homozygotes for the wild-type allele
      (*1/*1 n = 2), heterozygotes (n = 3) for the CYP2C19*2 (*1/ *2) or for the
      CYP2C19*3 (*1/*3) and heterozygote (n = 1) for the two defects (*2/*3) were on
      average 450, 1007 and 6710 ng x h(-1) x ml(-1), respectively. The ratios of AUCs
      of omeprazole/5-hydroxyomeprazole for *1/*1, *1/*2 or *1/*3 and *2/*3 were 1, 2
      and 30, respectively. In the repeated-dose study, the AUCs of omeprazole for * 1/
      *1, *1/*2 or *1/*3 and *2/*3 were 4041 (n = 2), 3149 (n = 3) and 6684 (n = 1) ng
      x h(-1) x ml(-1), respectively. The ratios of AUCs of omeprazole/5
      hydroxyomeprazole for *1/*1, * 1/*2 or * 1/*3 and *2/*3 were7, 11 and 30,
      respectively. In the repeated-dose study, the AUC of omeprazole of * 1/*1
      genotypes was nine-fold higher, that of *1/*2 and *1/*3 genotypes was three-fold
      higher, and the Cmax value of omeprazole was three-fold higher compared with
      subjects with the same genotype in the single-dose study. However, there were few
      differences in the AUC and Cmax of omeprazole between the *2/*3 genotype in the
      single-dose study and the homozygote for the CYP2C19*2 (*2/*2) in the repeated
      dose study. CONCLUSION: Subjects with *1/*1, *1/*2 and *1/*3 genotypes in the
      repeated-dose study had lower CYP2C19 activity than subjects of the same genotype
      in the single-dose study. The difference in omeprazole metabolism between
      subjects with different genotypes observed on day 1 seemed to disappear after 7
      days of repeated-dose administration.

PMID- 10206084
TI  - Pharmacokinetics of oxypolygelatine in healthy volunteers.
AB  - OBJECTIVE/METHODS: The pharmacokinetics of the plasma substitute oxypolygelatine
      (OPG) were studied in 12 healthy volunteers after single-dose administration of
      27 ml x kg(-1) body weight, with a maximum of 2000 ml. OPG was determined in
      plasma and urine over 48 h after the infusion. Peak plasma OPG concentrations at
      the end of the infusion were determined to 4.600 (623) microg x ml(-1), the area
      under the plasma concentration/time curve (AUC(0-infinity)) was calculated to
      70.135 (15.861) microg x h x ml(-1). RESULTS: The model-independently calculated
      volume of distribution came to 23.1 (4.8) 1 with a clearance total is (Cl(tot))
      of 24.6 (6.8) ml x min(-1). The initial half-life according to a three
      compartment model came to 0.3 (0.2) h, followed by a distribution half-life of
      3.1 (2.6) h and a terminal elimination half-life of 13.4 (2.2) h. Cumulative
      urinary excretion of OPG was 64% after 48 h. CONCLUSION: This low recovery rate
      may be explained by the distribution of OPG into the extravascular space and
      subsequent degradation in tissue sites.

PMID- 10206085
TI  - Systemic exposure to rosiglitazone is unaltered by food.
AB  - OBJECTIVE: To evaluate the effect of food on the bioavailability and
      pharmacokinetics of the insulin sensitizer rosiglitazone. METHODS: In a
      randomized, open-label, period-balanced, single-dose, crossover study,
      rosiglitazone 2 mg was administered to 12 healthy male volunteers either in the
      fasting state or following a standard high-fat breakfast. The primary end points
      of the study were AUC(0-inf) and Cmax. RESULTS: Single oral doses of
      rosiglitazone were safe and well tolerated. Overall exposure to rosiglitazone was
      unaffected by food. The geometric mean ratio of AUC(0-inf) in the fed:fasted
      regimens was 0.94 (95% CI: 0.82, 1.06); t1/2 was unaffected. Absorption of
      rosiglitazone in the fed state was more gradual and sustained than in the fasted
      state. Cmax was reduced by approximately 20% (point estimate 0.80; 95% CI 0.65 to
      0.97) and tmax was modestly delayed in the fed state. CONCLUSION: These data
      support dosing guidelines that will permit the administration of rosiglitazone
      without regard to meals for treatment of type 2 diabetes mellitus.

PMID- 10206086
TI  - The effect of ketoconazole on the pharmacokinetics, pharmacodynamics and safety
      of nisoldipine.
AB  - OBJECTIVE: The primary aim of the present study was to investigate the effect of
      ketoconazole on the pharmacokinetics of nisoldipine. METHODS: A single dose of
      nisoldipine 5 mg immediate-release tablet was administered either alone or in
      combination with ketoconazole 200 mg (4 days pretreatment and concomitant
      administration) in a randomized crossover trial in seven healthy male Caucasian
      volunteers. Plasma concentration-versus-time profiles of nisoldipine and its
      metabolite M9 were determined. RESULTS: Pre-treatment with and concomitant
      administration of ketoconazole resulted in a 24-fold and 11-fold, increase in
      mean AUC and Cmax of nisoldipine, respectively, compared with treatment with
      nisoldipine 5 mg alone. The ketoconazole-induced increase in plasma concentration
      of the metabolite M9 was of similar magnitude. CONCLUSION: The interaction is
      attributed to inhibition of cytochrome 3A4-mediated first-pass metabolism.
      Ketoconazole and other antifungal drugs of the substituted imidazole type as well
      as other potent inhibitors of cytochrome 3A4 should not be used concomitantly
      with nisoldipine.

PMID- 10206087
TI  - Pharmacokinetics and pharmacodynamics of clevidipine in healthy volunteers after
      intravenous infusion.
AB  - OBJECTIVE: To determine the pharmacokinetics and pharmacodynamics of clevidipine,
      a new ultrashort-acting calcium antagonist, in healthy male volunteers following
      a constant rate infusion. METHODS: Eight healthy male volunteers received 1030
      nmol x min(-1) of clevidipine together with a tracer dose of 3[H]-clevidipine for
      1 h as an i.v. infusion. Frequent venous blood samples and effect recordings were
      obtained during ongoing infusion and up to 32 h following termination of the
      infusion. The excretion of radioactivity in urine and faeces was followed for 7
      days. RESULTS: A two-compartment model gave the best fit to the individual
      clevidipine blood levels, resulting in a mean blood clearance of 0.14 (0.03) l x
      min(-1) x kg(-1) and a mean volume of distribution at steady state of 0.6 (0.1) l
      x kg(-1). The initial half-life was 1.6 (0.3) min, and the terminal half-life was
      15 (5) min. The maximum concentration of the metabolite H 152/81 was reached 2.2
      (1.3) min following termination of the infusion. The mean terminal half-life of
      the inactive primary metabolite was 9.5 (0.8) h and the mean recovery of the
      radioactive dose reached 83 (3)%. Following termination of the 1 h infusion, the
      effect on blood pressure (BP) and heart rate was back to pre-dose values within
      15 min. CONCLUSION: Clevidipine is a high clearance drug, which is rapidly
      metabolized to the corresponding inactive acid. The tmax value of the primary
      metabolite, and a virtually identical value of the initial half-life and the half
      life for elimination from the central compartment, indicate that the initial
      rapid decline of the post-infusion blood levels is mainly due to elimination
      rather than distribution. The duration of action of clevidipine is short.

PMID- 10206088
TI  - Utilization of cardiovascular drugs (blood pressure lowering drugs, lipid
      lowering drugs and nitrates) and mortality from ischaemic heart disease and
      stroke. An ecological analysis based on Sweden's municipalities.
AB  - OBJECTIVE: To perform an ecological study in an effort to generate questions
      concerning the preventive impact of various cardiovascular drugs on mortality
      from stroke and ischaemic heart disease (IHD) in the community, and to explore
      the association between sales of nitrates and mortality from stroke and IHD.
      METHODS: Out-patient drug utilization (sales) of blood pressure lowering drugs,
      lipid lowering drugs and nitrates were categorized in four groups of equal size
      by quartiles and compared with mortality from IHD and stroke, using the group of
      municipalities with the lowest utilization as reference, from 1989 to 1993 in 283
      of Sweden's 288 municipalities, by Poisson regression. Adjustments were made for
      population size, age and gender proportions, the utilization rate of
      cardiovascular drugs other than the tested drug group and location of the
      municipality. RESULTS: Compared with the group of municipalities with the lowest
      sales and adjusting only for population size, mortality from IHD and stroke
      increased with the extent of utilization of blood pressure lowering drugs and
      nitrates. In contrast, mortality decreased with increased utilization of lipid
      lowering drugs. After further adjustments by percentage of men, age structure,
      geographical location (mid-points) of the municipalities, and, as a proxy for
      cardiovascular disease, the sales of cardiovascular drugs other than the tested
      drug group, the increased risk associated with blood pressure lowering drugs
      disappeared, and there was a dose-response association between sales of diuretics
      and old antihypertensives and decreasing mortality, sales of nitrates continued
      to be associated with an increased risk, and the low mortality risk associated
      with sales of lipid lowering drugs persisted. CONCLUSION: Lipid lowering drugs
      may have a preventive impact in the general population, but the preventive impact
      of blood pressure lowering drugs, with the exception of diuretics and old
      antihypertensives, may be low in many municipalities. The safety of nitrates
      needs more investigation at the individual level.

PMID- 10206089
TI  - Population pharmacokinetic analysis of pirmenol in healthy volunteers and
      patients with arrhythmia.

PMID- 10206090
TI  - Lack of kinetic interaction between digoxin and voglibose.

PMID- 10206091
TI  - Outpatient use pattern for ketorolac is distinct from comparator drugs.

PMID- 10206092
TI  - Evaluation of the Dade Behring N Latex Cystatin C assay on the Dade Behring
      Nephelometer II System.
AB  - The Dade Behring N Latex Cystatin C assay, a particle-enhanced nephelometric
      immunoassay for measuring serum cystatin C, was evaluated on the Dade Behring
      Nephelometer II. The assay time was 6 min and the throughput was 75 samples per
      hour. The sample volume was 40 microL and the measuring range was 0.25-7.90 mg/L.
      Imprecision studies revealed within-run CVs < 1.8% and between-run CVs < 1.8% in
      the concentration range 0.87-4.63 mg/L. Recovery was 92.4-101.3%. Linearity
      studies showed excellent correlation between the theoretical and obtained values.
      No interferences were detected from haemoglobin < 1.0 mmol/ L, bilirubin <512
      micromol/L and Intralipid <20 g/L. Stability of cystatin C in serum was 7 days at
      temperatures from 20 degrees C to 20 degrees C and 6 months at -80 degrees C.
      Measurements of cystatin C in heparin-plasma and EDTA-plasma did not differ
      significantly from cystatin C measured in serum. Fifty patient samples run on the
      Dade Behring Nephelometer II (y) were compared to the Dako Cystatin C assay (x).
      The Passing-Bablok regression analysis revealed y = 1.105x - 0.340. In
      conclusion, the Dade Behring N Latex Cystatin C assay was precise and correlated
      with the Dako Cystatin C assay.

PMID- 10206093
TI  - Mechanical conversion of post-ischaemic ventricular fibrillation: effects on
      function and myocyte injury in isolated rat hearts.
AB  - Ventricular fibrillation (VF) and ventricular tachycardia (VT) are common
      phenomena during reperfusion. In experimental research many hearts have to be
      excluded from haemodynamic evaluation because of severe arrhythmias.
      Theoretically, electroconversion or mechanical conversion (MC) might be used to
      convert VF or VT. MC induces a physical shock analogous to a chest thump. The aim
      of this study was to investigate the efficacy of MC in isolated, perfused rat
      hearts, and to see whether MC itself induced myocardial cell injury and
      functional impairment. Langendorff-perfused rat hearts (n = 89) from several
      experimental series subjected to 30 min of global ischaemia and 60 min of
      reperfusion were retrospectively analysed. Left ventricular systolic (LVSP), end
      diastolic (LVEDP), and developed (LVDP) pressures, coronary flow (CF), and heart
      rate (HR) were measured. If VF or VT continued for 1 min during reperfusion, MC
      was attempted by a flick of the forefinger to the right ventricle. If VF or VT
      still occurred, MC was repeated. Hearts that did not have regular beating after
      20 min of reperfusion were excluded. Release of cardiac troponin T (cTnT) was
      measured before ischaemia and after 20 min of reperfusion. Forty-four out of 89
      hearts had VF or VT during reperfusion. Thirty-five hearts were converted, 18 of
      which were converted by one or two MCs only. The higher the total number of MCs
      employed, the more cTnT was released. After 20 min of reperfusion, LVEDP, LVDP
      and CF were better in hearts with a higher number of MCs and with increased
      release of cTnT. After 60 min of reperfusion, LVEDP was still improved in hearts
      with more cTnT release, whereas LVSP was lower, and LVDP and CF were independent
      of the number of MCs. There was no consistent correlation between release of cTnT
      and heart dysfunction. In conclusion, MC effectively converted VF or VT. MCs
      increased post-ischaemic myocardial cell damage, as judged from increased cTnT
      release. Post-ischaemic dysfunction was partly attenuated in hearts with multiple
      MCs, and did not correlate with release of cTnT. We feel that MCs should not be
      used in isolated, perfused hearts.

PMID- 10206094
TI  - Endothelin plays an important role in the endothelium-dependent vasodilatation in
      the human forearm.
AB  - Endothelium-dependent vasodilatation (EDV) in humans has been evaluated mainly by
      local infusion of a muscarinic-receptor agonists in the forearm. It has been
      postulated that the function of the vasodilator nitric oxide (NO) can be
      evaluated with this technique. However, the role of the vasoconstrictor
      endothelin in this model has not been investigated. METHODS: Ten male
      hypertensive and seven male normotensive subjects were subjected to measurements
      of forearm blood flow (FBF) by venous occlusion plethysmography during local
      intra-arterial infusion of metacholine (4 microg/min) or nitroprusside (10
      microg/min). In parallel, forearm venous plasma endothelin (ir-ET) was
      determined. RESULTS: Metacholine and nitroprusside increased FBF 2.3 and 2.2
      times the baseline level (6.6+/-2.8 SD ml/min/100 ml tissue) in hypertensive
      subjects and 5.1 times the baseline level (2.7+/-3.0 ml/min/100 ml tissue) for
      both drugs in the normotensive subjects. None of the drugs induced any
      significant changes in ir-ET levels in any of the groups (baseline 1.5+/-0.4
      pmol/l in hypertensive and 1.1+/-1.2 pmol/l in normotensive subjects). However,
      in the hypertensive subjects, the individual change in venous ir-ET levels during
      infusion with metacholine, but not with nitroprusside, was inversely related to
      the degree of vasodilatation induced by this agent (r = -0.71, p < 0.02). A
      similar correlation coefficient (r=-0.69) was found in healthy subjects.
      CONCLUSION: Muscarinic-receptor-agonist-stimulated vasodilatation in the human
      forearm, thought mainly to reflect NO synthesis, was inversely related to the
      change in endothelin levels, suggesting an important role for this endothelium
      derived vasoconstrictor in this model of EDV.

PMID- 10206095
TI  - Balance of non-metabolizable base in continuous peritoneal dialysis patients.
AB  - Acid generation and elimination processes compared to titratable non
      metabolizable base (NaOH equivalents, NB) turnover in end-stage renal disease
      patients are examined in the light of the Law of electroneutrality. The
      application over 2 days of the whole-body NB balance technique to 18 patients
      undergoing continuous ambulatory peritoneal dialysis is evaluated. The results
      show that the mean rate of NB loss with peritoneal effluent (as bicarbonate and
      organic acid anions) exceeded the mean rate of NB gain with the dialysis fluid
      (as salts of lactic acid) by 24 (27), m (SD), mmol per 2 days. In spite of this,
      the bicarbonate and pH of the plasma remained stable and within normal limits.
      The concurrent mean rate of the intestinal NB absorption was about 61 (27) mmol
      per 2 days, as calculated from the whole body balances of the several
      electrolytes in the metabolic steady-state. This intestinal absorption was more
      than sufficient to restore the body base consumed in neutralizing endogenous acid
      generation: 37 (14), 2H2SO4 mmol per 2 days, the remaining NB being eliminated as
      bicarbonate and organic acid anions. The ample spectrum of plasma acid-base (A B)
      values appears to some extent influenced by patient-related factors, such as the
      rate of drinking water intake and the set point deviation for organic acid
      turnover.

PMID- 10206096
TI  - Open laboratory information systems: a case study.
AB  - The EU-AIM project "OpenLabs" specified an open systems architecture for a
      clinical laboratory information system (LIS) environment and coined the term
      "open LIS". Since this conception has not yet been realized into systems and
      modules commercially available, two university hospitals in Norway had to specify
      an alternative model for openness when they, in a joint project, screened the
      market for a new LIS. To be open, a LIS must be (1) based on main-trend hardware
      and system software running under a standardized operating system, (2) designed
      for network-based distributed computing, (3) have sufficient documentation
      available to local staff, (4) be configurable through parameters, tables and
      scripts, and (5) have general and configurable access mechanisms both to real
      time processes and to the database. The present study describes the selection
      process and examines the compliance of the selected LIS (NetLab) with this model
      of openness. It is shown that local staff have been able to adapt this LIS to
      various and changing requirements in the laboratory.

PMID- 10206097
TI  - Circulating ionized calcium and parathyroid hormone levels following coronary
      artery by-pass surgery.
AB  - In critically ill patients, hypocalcaemia is a common finding. Also variable
      derangements in the normally tight Ca2+-mediated control of the parathyroid
      hormone (PTH) secretion have been found. Utilizing coronary artery by-pass
      grafting (CABG) as a standardized model of severe trauma, 18 patients underwent
      determinations of blood levels of calcium, magnesium (Mg), ionized calcium
      (Ca2+), serum levels of intact PTH, procalcitonin (PCT) and the proinflammatory
      cytokines tumour necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6).
      Samples were collected before, directly after, the morning after and 5 days after
      surgery. A significant, but minor, decrease in blood Ca2+ levels (mean 0.04
      mmol/L, p<0.05) was seen shortly after CABG, not accompanied by any significant
      change of serum PTH levels. This alteration of the Ca2+ control of the steady
      state PTH levels contrasted with the maintenance of the PTH secretory response to
      a sequential citrate and calcium infusion (CiCa clamp), which was normal in two
      patients evaluated in the morning following surgery. Serum Mg levels were
      transiently increased after operation (+0.25 mmol/L, p<0.001) and correlated to
      the TNF-alpha (r=0.62, p <0.01) and PCT (r=0.67, p < 0.006) levels in the morning
      after surgery. Serum levels of IL-6 and TNF-alpha were significantly (p < 0.0001)
      increased immediately after surgery, while the peak in serum PCT levels (p <
      0.001) occurred in the morning after CABG. Serum PTH levels correlated positively
      with IL-6 (r=0.68, p<0.008) 5 days after surgery. In conclusion, CABG caused a
      decrease in ionized calcium levels without a rise in steady-state PTH levels, but
      rapid changes in Ca2+ during CiCa clamping revealed a normal PTH secretory
      response. These findings might relate to elevated serum Mg levels, while a direct
      action of TNF-alpha or IL-6 on the PTH release seem less possible.

PMID- 10206098
TI  - Part of prekallikrein removed from human plasma together with IgG--immunoblot
      experiments and functional tests.
AB  - With the present study, evidence is provided that prekallikrein (PK) in human
      plasma might be present in two different states, one of them removed along with
      IgG on Protein G columns. At a plasma dilution of 1 + 2.5, small amounts of an
      IgG fraction were left in plasma along with all of the PK. At a dilution of 1 +
      11, nearly all IgG was removed. The removal in parallel of part of the PK was
      shown in immunoblot experiments and confirmed in amidase assays. One monoclonal
      antibody against PK (13G11) and two preparations of polyclonal antibodies were
      used for the immunoblot experiments. Different peptide substrates (S-2302, S
      2222, Bz-Pro-Phe-Arg-pNA), along with protease inhibitors (soybean trypsin
      inhibitor, corn trypsin inhibitor, lima bean trypsin inhibitor) were used for the
      amidase assays. The amidase assays indicated that factors XII and XI were reduced
      by Protein G columns. In all experiments with extensive removal of IgG, protein
      recognized by the factor XII light chain mAb C6B7 was removed at the same time.
      This antibody preparation did not detect purified contact factors, but it did
      recognize a preparation of purified beta-FXIIa, and also significant amounts of
      protein present in plasma deficient in factor XII and not detectable in plasma
      deficient in PK. This protein accordingly seems to be connected with the PK
      fraction removed with IgG.

PMID- 10206099
TI  - Influence of iron deficiency anaemia on haemoglobin A2 levels: possible
      consequences for beta-thalassaemia screening.
AB  - Iron deficiency modulates the synthesis of HbA2, resulting in reduced HbA2 levels
      in patients with iron deficiency anaemia. The diagnosis heterozygous beta
      thalassaemia is based on a raised HbA2 level. Patients with beta-thalassaemia and
      concomitant iron deficiency can show normal HbA2 levels. It is of clinical
      importance to know the quantitative effect of iron-deficient erythropoiesis on
      the levels of HbA2 in order to be able to determine which iron-deficient patients
      with normal HbA2 levels have to be retested after iron therapy in thalassaemia
      screening programmes. In this study, HbA2 levels in 150 patients with iron
      deficiency anaemia and 71 healthy controls have been measured. A linear
      correlation is found in the patient group between HbA2 and Hb, HbA2 and MCV, and
      HbA2 and erythrocyte zinc protoporphyrin (ZPP). In future studies, the
      correlation between HbA2 and erythrocyte parameters in patients with heterozygous
      beta-thalassaemia and concomitant iron deficiency has to be examined. We
      recommend that ZPP be measured in these studies too, as ZPP levels may be a
      better indicator of concomitant iron deficiency than Hb or MCV in thalassaemic
      patients.

PMID- 10206101
TI  - Serosurvey on theileriosis in Awassi sheep in Syria.
AB  - A serological survey using indirect fluorescent antibody test (IFAT) for
      Theileria spp. infection of sheep has been carried out from 1994 to 1997 in the
      provinces Daraa, Hama, Homs and Latakia in Syria. The results revealed a mean
      seroprevalence of 59.9% without significant differences between years (p = 0.57)
      and provinces (p = 0.126).

PMID- 10206100
TI  - Administration of toltrazuril during experimental coccidiosis in mule ducks:
      comparison of the efficacy of a single administration at two different endogenous
      stages.
AB  - An experimental Eimeria mulardi coccidiosis was reproduced in mule ducks. A
      single dose of toltrazuril (7 mg per kg) was administered at two different
      endogenous stages: Day 2 (first meronts) or Day 5 (last meronts and gamonts). The
      efficacy of the drug was assessed on four criteria (body weight, oocyst counts,
      macroscopic lesions, and presence of the meronts and gamonts). To have a curative
      effect, a single dose of toltrazuril should be administered early on. However, a
      single treatment on Day 5 had a prophylactic effect.

PMID- 10206102
TI  - Serum antibody response of Castellana sheep to Haemonchus contortus infection and
      challenge: relationship to abomasal worm burdens.
AB  - Primary and secondary serum antibody responses to Haemonchus contortus were
      studied in Castellana sheep. Ten-month-old sheep were infected (200 L3/kg live
      weight (lw)) and challenged (400 L3/kg lw) or uninfected and equally challenged
      with H. contortus. Primary infections induced a partially protective response
      upon challenge, characterized by higher serum protein levels, longer prepatent
      periods, lower fecal egg counts, and significant reduction in the establishment
      rate of the parasite and abomasal adult and L4 worm burdens. The resistant status
      of the infected and challenged sheep was not clearly related either to the serum
      specific antibody levels (IgG: IgG1, IgG2; IgM; IgA) estimated by ELISA or to
      immunodetection patterns in the Western blots.

PMID- 10206103
TI  - Study on the inductive factors of hypobiosis of Ostertagia ostertagi in cattle.
AB  - Two experiments were carried out to determine the causes producing the Ostertagia
      ostertagi hypobiosis phenomenon in cattle. In the first experiment, the effect of
      time on third-stage larvae in the environment was studied during a 2-year period.
      Three experimental paddocks contaminated with O. ostertagi eggs at different
      times of the year were used, and the levels of hypobiosis were recorded by using
      'indicator' and 'tracer' calves. The results suggest that time as such is not a
      hypobiosis-inductive factor. The second experiment was conducted under laboratory
      conditions, where the effects of temperature and light on infective larvae were
      studied. Infective larvae were subjected to different conditions of temperature
      and light during 6 weeks, and then inoculated to parasite-naive calves, which
      were slaughtered after 4 weeks. Percentages of hypobiotic larvae in these calves
      varied from 3.5 to 94.8%, depending on the different storage conditions the
      larvae underwent before inoculation. Results suggest that increasing temperature
      and increasing time of light exposure simulating spring conditions would be the
      factors which act upon third-stage larvae inducing them to a later hypobiotic
      stage in the host.

PMID- 10206104
TI  - Biological parameters of Trichostrongylus colubriformis in Meriones unguiculatus.
AB  - In a series of three experiments, 64 jirds, Meriones unguiculatus, were infected
      with 700 infective larvae of Trichostrongylus colubriformis for the study of
      several biological parameters of this laboratory host-parasite model. In jirds
      the third stage larvae of T. colubriformis were shown to reach the fourth larval
      stage by the Day 6 post-infection (PI). By Day 10 PI, all the worms harvested had
      reached the immature adult stage. All immature adult stages of T. colubriformis
      developed to sexually mature adult stage by Day 12 PI when the female worms
      showed developing eggs in their uteri. Developed eggs were observed in the uteri
      of females on Days 13 and 14 PI. The first eggs of T. colubriformis appeared in
      the faeces of jirds on Day 13 PI. The peaks of egg production were recorded
      between Day 21 and Day 31 PI. Immunosuppression of jirds infected with 700 L3, by
      administration of dexamethasone from Day 57 to Day 94 PI led to increased faecal
      egg count when compared to untreated controls. All the worms were located in the
      small intestine. The jirds of dexamethasone treated group harboured higher number
      of adult worms than those of the untreated group. The number of adult worms was
      significantly higher in the first part of the small intestine than in the three
      other similar parts of the small intestine. The coefficient of correlation
      between the faecal egg count and worm number on the day of necropsy of jirds
      ranged between r = 0.58 and r = 0.89. Patent infections in jirds were maintained
      till the end of experiment on Day 100 PI, indicating that in this host and unlike
      other laboratory hosts, T. colubriformis is responsible for long lasting
      infections similar to what happens in domestic ruminants. The results of the
      present study suggest that the jird is a suitable laboratory model to study
      various aspects of this host-parasite relationship.

PMID- 10206105
TI  - Spatial distribution and spread of sheep biting lice, Bovicola ovis, from point
      infestations.
AB  - The spatial distribution of chewing lice (Bovicola ovis) on their hosts was
      examined in Polypay and Columbia ewes initially artificially infested on the
      midside or the neck. Densities of lice were determined at 69 body sites in eight
      body regions at approximately monthly intervals for 2 years. In the second year,
      half of the ewes were mated and lice were counted at 26 body sites on the
      resulting lambs. Polypay ewes had higher densities of lice than Columbias at most
      inspections but there was little effect of infestation point or mating on either
      numbers or the distribution of lice. During periods of high louse numbers
      densities were generally greatest on the sides or the back. Densities on the head
      were also high at times and peaked later than overall louse densities. Shearing
      markedly reduced density but increased the proportion of lice found on the neck,
      belly and lowleg sites. The distribution of lice on the lambs was similar to that
      on the ewes except that fewer lice were found on the head. Comparisons of lice
      per part with the numbers of lice extracted from clipped patches indicated that a
      sheep with wool bearing area of 1 m2 and a mean count of one louse per 10 cm
      fleece parting carried approximately 2000 lice. At most times of the year
      inspections for sheep lice should be concentrated on the sides and back, but in
      recently shorn sheep greater attention should be paid to the lower neck and
      ventral regions. Implications of the observed distributions of lice for the
      efficacy of chemical treatments are discussed.

PMID- 10206106
TI  - Activity of a deltamethrin shampoo against Ctenocephalides felis and
      Rhipicephalus sanguineus in dogs.
AB  - A controlled clinical trial was undertaken to assess the efficacy of an
      application of a 0.07% deltamethrin shampoo against fleas and ticks in dogs.
      Twenty beagles, housed in separate cages, were randomly allocated into two groups
      of 10. The dogs were infested with 50 Ctenocephalides felis and 50 Rhipicephalus
      sanguineus each, and parasites were counted 24 h (fleas) and 72 h (ticks) later
      (Day 0). Dogs, when state, were then treated with 25 ml of a shampoo containing
      0.07% deltamethrin (Group 1). Dogs in Group 2 were the controls. Fleas and ticks
      were counted 24 h (Day 1) and 48 h (Day 2) after the shampoo was applied, and the
      parasites were then removed. All the dogs were reinfested with fleas and ticks on
      Days 2, 7, 9, 14, 16 and 20. Parasites were counted 24 and 48 h after each
      reinfestation. Effectiveness against fleas was calculated 24 h after infestation,
      and against ticks 48 h after infestation. This study showed that the application
      of 25 ml of shampoo containing 0.07% deltamethrin to beagle dogs weighing between
      10.2 and 12 kg was very well tolerated. It controlled the parasites present on
      the animals at the time of application: with an efficacy of 100% against fleas 24
      h after treatment and an efficacy of 95% against ticks 48 h after treatment. The
      treatment protected against flea reinfestations with an efficacy of 100% during
      the first week, >98% in the second week and >95% in the third week. It also gave
      >99% protection against tick reinfestations in the first week and >96% in the
      second week.

PMID- 10206107
TI  - Studies on coccidiosis in goats in Poland.
AB  - The study was carried out in a flock consisting of 110 goats. Nine species of
      coccidia were found: Eimeria christenseni, E. arloingi, E. jolchijev, E.
      ninakohlyakimovae, E. alijevi, E. apsheronica, E. caprina, E. caprovina and E.
      hirci. Eighty-one percent of adults and 100% of kids were infected. Number of
      oocysts per gram of feces in kids ranged form 1200 to 202000. Clinical symptoms
      in about 50% of kids were observed. Toltrazuril (Baycox, Bayer), 20 mg/kg of body
      weight was highly efficacious in therapy of goat coccidiosis.

PMID- 10206108
TI  - Radial basis function neural networks for the characterization of heart rate
      variability dynamics.
AB  - This study introduces new neural network based methods for the assessment of the
      dynamics of the heart rate variability (HRV) signal. The heart rate regulation is
      assessed as a dynamical system operating in chaotic regimes. Radial-basis
      function (RBF) networks are applied as a tool for learning and predicting the HRV
      dynamics. HRV signals are analyzed from normal subjects before and after
      pharmacological autonomic nervous system (ANS) blockade and from diabetic
      patients with dysfunctional ANS. The heart rate of normal subjects presents
      notable predictability. The prediction error is minimized, in fewer degrees of
      freedom, in the case of diabetic patients. However, for the case of
      pharmacological ANS blockade, although correlation dimension approaches indicate
      significant reduction in complexity, the RBF networks fail to reconstruct
      adequately the underlying dynamics. The transient attributes of the HRV dynamics
      under the pharmacological disturbance is elucidated as the explanation for the
      prediction inability.

PMID- 10206109
TI  - Using Boolean reasoning to anonymize databases.
AB  - This paper investigates how Boolean reasoning can be used to make the records in
      a database anonymous. In a medical setting, this is of particular interest due to
      privacy issues and to prevent the possible misuse of confidential information. As
      electronic medical records and medical data repositories get more common and
      widespread, the issue of making sensitive data anonymous becomes increasingly
      important. A theoretically well-founded algorithm is proposed that via cell
      suppression can be used to make a database anonymous before releasing or sharing
      it to the outside world. The degree of anonymity can be tailored according to the
      specific needs of the recipient, and according to the amount of trust we place in
      the recipient. Furthermore, the required measure of anonymity can be specified as
      far down as to the individual objects in the database. The algorithm can also be
      used for anonymization relative to a particular piece of information, effectively
      blocking deterministic inferences about sensitive database fields.

PMID- 10206110
TI  - Case-based prediction in experimental medical studies.
AB  - Case-based approaches predict the behaviour of dynamic systems by analysing a
      given experimental setting in the context of others. To select similar cases and
      to control adaptation of cases, they employ general knowledge. If that is neither
      available nor inductively derivable, the knowledge implicit in cases can be
      utilized for a case-based ranking and adaptation of similar cases. We introduce
      the system OASES and its application to medical experimental studies to
      demonstrate this approach.

PMID- 10206111
TI  - Predicting coronary disease risk based on short-term RR interval measurements: a
      neural network approach.
AB  - Coronary heart disease is a multifactorial disease and it remains the most common
      cause of death in many countries. Heart rate variability has been used for non
      invasive measurement of parasympathetic activity and prediction of cardiac death.
      Patterns of heart rate variability associated with respiratory sinus arrhythmia
      have recently been considered as possible indicators of coronary heart disease
      risk in asymptomatic subjects. The aim of this work is to detect individuals at
      varying risk of coronary heart disease based on short-term heart rate variability
      measurements under controlled respiration. Artificial neural networks are used to
      recognise Poincare-plot-encoded heart rate variability patterns related to
      coronary heart disease risk. The results indicate a relatively coarse binary
      representation of Poincare plots could be superior to an analogue encoding which,
      in principle, carries more information.

PMID- 10206112
TI  - A neural network approach to the diagnosis of morbidity outcomes in trauma care.
AB  - This paper introduces the application of artificial neural networks to trauma
      complications assessment. The potential financial benefits of improving on trauma
      center diagnostic specificity in complications assessment are illustrated and the
      operational feasibility of the use of diagnostic neural models across
      institutions is discussed. A prototype neural network model is described, which,
      after training, succeeds in diagnosing the complication of sepsis in victims of
      traumatic blunt injury. Its diagnostic performance with 100% sensitivity and
      96.5% specificity is accomplished with test data from a regional trauma center.
      The model is further shown to have correctly detected, during training,
      incorrectly coded data. The potential this suggests, for parsimonious database
      scrubbing through the use of neural network models, is discussed.

PMID- 10206113
TI  - Advances in fuzzy theory.
AB  - Recent advances in the foundations of fuzzy theory facilitated by Bart Kosko's
      discovery of the fuzzy hypercube are of high relevance to artificial intelligence
      in medicine research. The new concepts of set inclusion, equality, and similarity
      are therefore reported in this paper. A unifying notion of a Lotfi Zadeh space is
      also introduced to show that Bart Kosko's fuzzy hypercube is a Zadeh space.

PMID- 10206114
TI  - Isolation of Trypanosoma brucei from the monitor lizard (Varanus niloticus) in an
      endemic focus of Rhodesian sleeping sickness in Kenya.
AB  - Monitor lizards were sampled along the shores of Lake Victoria to detect natural
      infections of potentially human-infective trypanosomes. In an area with endemic
      rhodesian sleeping sickness, one of 19 lizards was infected (Busia, Kenya). Six
      of ten lizards also showed indirect evidence of infection with Trypanosoma brucei
      (antibody ELISA). In an area with no recent history of human disease (Rusinga
      Island), no parasites were found and no antibodies to T. brucei were detected.
      The isolate was identified as T. brucei through xenodiagnosis (completion of the
      life cycle in the salivary glands of tsetse), and through molecular techniques
      (positive reactions with a PCR primer and a microsatellite DNA probe
      characteristic of the subgenus Trypanozoon). Experimental infections of monitor
      lizards were also attempted with a variety of parasites and tsetse species. It
      was possible to infect monitor lizards with T. brucei but not with forest or
      savannah genotypes of Trypanosoma congolense. Parasites reached low levels of
      parasitaemia for a short period without generating any pathology; they also
      remained infective to tsetse and laboratory rats. The implications of these
      findings are discussed in relation to the endemicity of sleeping sickness.

PMID- 10206115
TI  - Rapid DNA extraction for molecular epidemiological studies of malaria.
AB  - DNA isolation from blood samples collected in molecular epidemiological studies
      is crucial for the quality and reproducibility of data. Blood samples from two
      malaria endemic sites have been prepared by four different DNA isolation methods
      with subsequent PCR amplification of the msp2 locus of Plasmodium falciparum. We
      tested a rapid boiling method; the guanadine isothiocyanate DNA extraction; QIAmp
      blood kit; and the ISOCODE STIX PCR template preparation dipstick, and analysed
      the numbers of concurrent infections/sample. The rapid boiling method and the
      ISOCODE STIX provided overall the best sensitivity combined with ease of
      handling. The possibility to store and ship the ISOCODE STIX at ambient
      temperature adds further advantage to this method.

PMID- 10206116
TI  - Eosinophils, eosinophil cationic protein and eosinophil-derived neurotoxin in
      serum and urine of patients with onchocerciasis coinfected with intestinal
      nematodes and in urinary schistosomiasis.
AB  - Eosinophils, eosinophil cationic protein (ECP), eosinophil-derived neurotoxin
      (EDN/EPX), myeloperoxidase (MPO) and IgE were measured in blood, serum and/or
      urine in Schistosoma haematobium- and Onchocerca volvulus-infected Guineans and
      O. volvulus- and S. haematobium-negative Guineans coinfected or infected with
      intestinal nematodes. The number of eosinophils and levels of eosinophil granule
      proteins but not of MPO were found to be strongly elevated in all Africans as
      compared to European controls. The highest serum ECP and serum and urinary
      EDN/EPX levels were observed in the hyperreactive form of onchocerciasis (sowda).
      Onchocerciasis patients and O. volvulus-negative Africans coinfected or infected
      with intestinal nematodes (hookworm and/or Ascaris lumbricoides) revealed higher
      serum granule protein concentrations and/or absolute eosinophil counts and
      urinary ECP than those without nematode infections. Statistical differences
      between both sections were found for the absolute eosinophil counts and for serum
      EDN/EPX and IgE in generalized onchocerciasis, and for urinary ECP in sowda,
      indicating stimulation of the eosinophil potential of O. volvulus-positive
      patients by coexistent hookworm infection. This worm species, in contrast to A.
      lumbricoides, causes especially high eosinophil counts and EDN/EPX and IgE
      levels. From these results it is concluded that in nematode diseases, ECP and
      EDN/EPX levels reflect the degree of antigenic stimulation, eosinophil activation
      and eosinophil turnover rates. Serum ECP and serum and urinary EDN/EPX may,
      therefore, serve as parameters to monitor helminth infection. Urinary ECP may be
      a marker of eosinophiluria secondary to urogenital manifestation of S.
      haematobium. It is elevated in hyperreactive onchocerciasis activated by
      intestinal nematodes.

PMID- 10206117
TI  - Rapid and reliable serological diagnosis of enteric fever: comparative
      sensitivity and specificity of Typhidot and Typhidot-M tests in febrile Malaysian
      children.
AB  - The Typhidot test, which detects IgM and IgG antibodies to a Salmonella typhi
      specific outer membrane protein, is as sensitive as, and more specific than, the
      Widal test in the diagnosis of enteric fever in Malaysian children. It is easier
      and quicker to perform. In order to increase diagnostic accuracy in an area of
      high endemicity, the Typhidot-M test has been developed in which IgG is first
      removed. This theoretically allows improved detection of IgM, and thus would
      differentiate new from recent infections. We evaluated both tests in 134
      unselected febrile children admitted to the General Hospital Kota Bharu,
      Malaysia. The children were divided into two groups: (i) those who were blood
      and/or stool culture positive for S. typhi and/or who had clinical features
      strongly suggestive of enteric fever (n = 62); and (ii) those who were both
      culture-negative and had clinical evidence of another diagnosis (n = 72). The
      sensitivity and specificity of the Typhidot and Typhidot-M tests were identical
      at 90.3 and 93.1%, respectively. Both tests had comparable sensitivity but
      greater specificity than those of the Widal test (91.9 and 80.6%, respectively).
      When used together, a positive result for Typhidot and/or Typhidot-M was more
      specific than either test alone (95.2%) but specificity was lower (87.5%). We
      conclude that the Typhidot and Typhidot-M tests have comparatively high
      diagnostic accuracy, suggesting that IgM can be detected in children who may have
      a predominant IgG response to S. typhi. Using these tests in combination
      increases the negative predictive value but at the cost of a lower positive
      predictive value.

PMID- 10206118
TI  - Immunochemotherapy with interferon-gamma and multidrug therapy for multibacillary
      leprosy.
AB  - Treatment for multibacillary leprosy is presently performed with a multidrug
      therapy (MDT) scheme maintained for 2 years. Leprosy treatment however can
      benefit from the reduction of length. The lack of interferon-gamma (IFN-gamma)
      production by lepromatous leprosy (LL) patients' lymphocytes lead us to use this
      cytokine in the treatment of multibacillary leprosy associated with MDT in the
      treatment of multibacillary leprosy, and monitor several clinical and
      immunological parameters during the course of treatment. A total of 20
      multibacillary leprosy patients were evaluated, 10 treated with MDT alone, and 10
      treated with MDT + 10 daily doses of 2 x 10(6) international units (IU) of
      recombinant human IFN-gamma/m2 followed by 10 daily doses of 10(7) IU IFN
      gamma/m2, intramuscularly, during the first 20 days of MDT. IFN-gamma was well
      tolerated and did not cause any increase in the rate of leprosy reactions
      development during treatment. Decrease of bacillary load, fall of anti
      Mycobacterium leprae IgG serum antibodies, changes of histological pattern, as
      well as changes in lymphocyte proliferation assay in response to mitogens (PHA or
      PWM), M. leprae antigen or PPD was similar in both groups of patients. Among
      several soluble immunological markers measured before and 30 days after beginning
      of treatment, levels of soluble IL-2R receptor increased in patients treated with
      MDT plus IFN-gamma whereas decreased in patients treated with MDT alone. Soluble
      ICAM-1 levels decreased in the MDT group but did not change in the MDT + IFN
      gamma treated patients. Soluble CD4 and soluble CD8 markers did not change
      significantly in either group of patients. Neopterin, a marker of macrophage
      activation, increased in all but one patient treated with MDT + IFN-gamma but in
      none treated with MDT alone, indicating that IFN-gamma was active in vivo. Our
      findings indicate that despite being able to promote macrophage activation in
      multibacillary leprosy patients a short course of systemically administered IFN
      gamma is not able to change the clinical course of a long standing disease such
      as leprosy.

PMID- 10206119
TI  - Species specific detection of Trypanosoma cruzi and Trypanosoma rangeli in vector
      and mammalian hosts by polymerase chain reaction amplification of kinetoplast
      minicircle DNA.
AB  - Several groups have recently developed molecular tests for the detection of
      Trypanosoma cruzi, the causative agent of Chagas' disease. Polymerase chain
      reaction (PCR) amplification of kinetoplast minicircle DNA sequences appears to
      be the most sensitive method. However, the specificity of PCR-based diagnostic
      methods was challenged when the complete sequence of Trypanosoma rangeli DNA
      minicircles was discovered. In the present study, we conducted. PCR experiments
      using the S35/S36 primers in Rhodnius prolixus and Balb/c mice with single and
      mixed infections of T. cruzi and/or T. rangeli. In single infections, the profile
      of each trypanosome was easily distinguishable in haemolymph, salivary gland and
      intestinal tissues and faeces of insect vectors. In mixed infections of anterior
      intestine (where T. rangeli is more predominant than T. cruzi), the DNA
      amplification profile of both parasites was observed simultaneously. Conversely,
      only the T. cruzi profile was observed in rectal ampulla (where T. cruzi is more
      abundant than T. rangeli). In mice with single infections of T. cruzi or T.
      rangeli, the profiles of amplified DNA were easily distinguishable in each case.
      The T. cruzi profile was dominant in most mixed infections, probably due to the
      fact that T. cruzi minicircles are more abundant and consequently compete more
      eagerly for annealing with the S35/S36 primers. In cases of mixed infections
      where T. rangeli was initially more abundant than T. cruzi, the specific T.
      rangeli 760 bp band was present for 7 days after infection and then this band and
      others ranging from 300 to 450 bp disappeared and only the typical T. cruzi 330
      bp band remained. The S35/S36 primers used in polyacrylamide gel electrophoresis
      (PAGE) detected T. cruzi specifically, and prevented misdiagnosis due to the
      presence of T. rangeli. This technique can also be used to identify parasites in
      different stages of the infection (acute or chronic) in vertebrate hosts and to
      localize the parasites in the insect vector.

PMID- 10206121
TI  - The health benefits of physical activity in children and adolescents:
      implications for chronic disease prevention.
AB  - Clinical, epidemiological and basic research evidence clearly supports the
      inclusion of regular physical activity as a tool for the prevention of chronic
      disease and the enhancement of overall health. In children, activities of a
      moderate intensity may enhance overall health, and assist in preventing chronic
      disease in at-risk youth. The numerous health benefits of regular exercise are
      dependent on the type, intensity and volume of activity pursued by the
      individual. These benefits include reduction of low density lipoproteins while
      increasing high density lipoprotein; improvement of glucose metabolism in
      patients with type II diabetes; improved strength, self esteem and body image;
      and reduction in the occurrence of back injuries. In addition, a progressive,
      moderate-intensity exercise program will not adversely effect the immune system
      and may have a beneficial effect on the interleukin-2/natural killer cell system.
      Furthermore, by decreasing sedentary behaviors and, thus, increasing daily
      physical activity, individuals may experience many stress-reducing benefits,
      which may enhance the immune system. CONCLUSION: Moderate intensity exercise of a
      non-structured nature seems to facilitate most of the disease prevention goals
      and health promoting benefits. With new guidelines promoting a less intense and
      more time-efficient approach to regular physical activity, it is hoped that an
      upward trend in the physical activity patterns, and specifically children at risk
      for chronic disease, will develop in the near future.

PMID- 10206120
TI  - Monitoring house reinfestation by vectors of Chagas disease: a comparative trial
      of detection methods during a four-year follow-up.
AB  - Domestic reinfestations by triatomine bugs were monitored after application of
      deltamethrin and apparent elimination of Triatoma infestans in Amama and other
      nearby rural villages, north-west Argentina, from 1992 to 1996. The five methods
      used were sensor boxes, sheets of pink typing-paper, timed manual catches by a
      skilled three-person team aided by a flushing-out agent, collections by house
      dwellers, and knockdown using insecticide fumigant canisters. In bedrooms, house
      dwellers collected T. infestans significantly more frequently than the flushing
      out method, but the reverse occurred in peridomestic sites. Both methods and
      sensor boxes revealed the frequent invasion of adult Triatoma guasayana and T.
      infestans, but neither T. guasayana nor Triatoma sordida colonized bedroom areas
      in spite of their rising abundance in nearby peridomestic sites. Sensor boxes
      were significantly more sensitive than the matched paper-sheets in three of five
      cross-sectional surveys. On average, each box recorded 2.0-3.2 times more
      triatomine fecal smears than each paper sheet. The frequency of dejecta in sensor
      boxes correlated positively with the proportion of houses where T. infestans, T.
      guasayana or T. sordida were captured by any method in bedroom areas. Triatomine
      fecal smears in sensor boxes were the earliest and most frequent sign of
      domiciliary infestation, followed by dwellers' collections of adult bugs.
      Analyzing the data prospectively, we provide a quantitative, predictive
      understanding of detection methods and review the validity and interpretation of
      the different signs of infestation obtained. The most sensitive and cost
      effective combination of detection methods for vector surveillance in domestic
      areas was the use of sensor boxes and house-dwellers collections.

PMID- 10206122
TI  - Fungal endocarditis in critically ill children.
AB  - All cases of infective endocarditis occurring from January 1990 to December 1996
      at our institution were reviewed, with a special focus on fungal endocarditis.
      Five critically ill children with fungal endocarditis and eleven children with
      bacterial endocarditis were recorded. The proportion of fungal endocarditis in
      our series was 5/16 (31%) and Candida albicans (4/5) was the most common fungal
      pathogen. Only one patient required heart surgery because of a loose patch but
      all the others were treated only by medical management for cure. The hospital
      survival rate was 80% (4/5) and the overall long-term survival rate was 60% (3/5)
      with only one death directly related to fungal infection. CONCLUSION: Despite the
      small number of cases, a sole medical approach including amphotericin B and long
      term fluconazole prophylaxis for the treatment of fungal endocarditis in
      critically ill children seems to offer an alternative to surgical treatment which
      may be kept for failure of medical treatment.

PMID- 10206123
TI  - Aortic valve regurgitation as the presenting sign of Takayasu arteritis.
AB  - Takayasu arteritis is a rare chronic vasculitis primarily involving the aorta and
      its main branches. We report an adolescent girl with Takayasu arteritis who
      presented with an isolated aortic valve regurgitation as part of a systemic
      inflammatory process. This patient was initially misdiagnosed as having rheumatic
      heart disease and the correct diagnosis was made only 1 year later. CONCLUSION:
      Takayasu arteritis should be considered among the diagnostic possibilities in
      patients who present with an unexplained systemic inflammatory syndrome and a
      cardiac murmur.

PMID- 10206124
TI  - Malignant pancreatic tumour within the spectrum of tuberous sclerosis complex in
      childhood.
AB  - A 12-year-old boy with tuberous sclerosis complex (TSC) presented with a large
      retroperitoneal tumour. Exploratory surgery revealed an infiltrative tumour
      originating from the pancreas, with local metastases to the lymph nodes. The
      histologal diagnosis was a malignant islet cell tumour. Retrospectively measured
      pancreatic hormone levels, however, were normal. A connection between the
      malignancy and TSC was demonstrated by loss of heterozygosity of the TSC2 gene in
      the tumour. The primary mutation Q478X in this patient was identified in exon 13
      of the TSC2 gene on chromosome 16. CONCLUSION: Pancreatic islet cell tumours have
      been mainly associated with multiple endocrine neoplasia syndrome type 1. In our
      case we demonstrate a direct relationship of this tumour to tuberous sclerosis
      complex, in the absence of further signs of multiple endocrine neoplasia syndrome
      type 1.

PMID- 10206125
TI  - Lymphocytic hypophysitis with central diabetes insipidus and consequent
      panhypopituitarism preceding a multifocal, intracranial germinoma in a
      prepubertal girl.
AB  - We report the clinical course of a prepubertal girl with central diabetes
      insipidus (DI) and consequent panhypopituitarism evolving over a period of 10
      years due to lymphocytic hypophysitis and subsequent germinoma. Two years after
      the diagnosis of central DI was established, MRI revealed a thickened pituitary
      stalk. Later pituitary enlargement and increasing thickening of the pituitary
      stalk impinging on the optic chiasm required a trans-sphenoidal biopsy which
      disclosed active hypophysitis with lymphocytic infiltrates and necrosis. High
      dose dexamethasone treatment only temporarily halted the disease process.
      Therefore, stereotactic radiation therapy was performed as a rescue treatment and
      MRI findings almost reversed. However, the subsequent MRI showed multiple
      intracranial lesions identified histologically as a germinoma and a standard
      chemotherapy and radiation was performed. CONCLUSION: The diagnosis of diabetes
      insipidus in children requires long-term follow up beyond the pubertal age in
      order to establish the underlying cause. In contrast to lymphocytic hypophysitis
      in adults, lymphocytic hypophysitis in prepubertal children may represent the
      first sign of a host reaction to an occult germinoma.

PMID- 10206126
TI  - Hepatitis B vaccination in preterm infants.
AB  - Preterm infants, especially those with very low birth weight, are at risk of
      hepatitis B virus infection. They often require invasive diagnostic methods in
      their first weeks of life, intensive treatment and long-term hospitalisation.
      Therefore, hepatitis B vaccination is particularly justified in these patients.
      Our aim was to determine the reaction of preterm children to hepatitis B
      vaccination. The study comprised 64 preterm children whose birth weight ranged
      from 700 g to 2460 g (mean 1776.6 g +/- 480.4 g) and whose gestational age was
      between 25 and 36 weeks. A 10 microg dose of the recombinant vaccine Engerix-B
      (SmithKline Beecham) was given at intervals of 0, 1, 2 and 12 months. In 49.2% of
      the children vaccination was administered on the 1st day of life, and in the
      remaining cases between the 2nd and 119th days post delivery. One month after
      vaccination completion the levels of anti-hepatitis B surface antigen (HBs)
      antibodies were evaluated. In 98.4% of the vaccinated preterm infants the level
      of antibodies was > 10 mIU/ml. Mean level of anti-HBs antibodies in the group of
      children with birth weight < or = 2000 g was 2431.4 mIU/ml, while in those with
      birth weight >2000 g it was 4803.9 mIU/ml. In children with a birth weight < or =
      1000 g, the mean level of anti-HBs antibodies was significantly lower than in
      those with birth weight >2000 g. The level of anti-HBs antibodies in children who
      started vaccination > 1 st day of life was significantly lower in preterm
      children with a birth weight < or = 2000 g than in those with a birth weight
      >2000 g. Although vaccination was started on the 1st day of his life, one child
      with birth weight of 2300 g developed a hepatitis B virus infection. One child
      did not respond to vaccination (anti-HBs < 10 mIU/ml) and in three cases the
      response was very poor (11 100 mIU/ml). These patients were given a supplementary
      booster double dose of Engerix B (20 microg). After 1 month the level of anti-HBs
      antibodies was evaluated again and high values of 657 mIU/ml to 14520 mIU/ml were
      observed. In the group of children with a birth weight < or = 1000 g the response
      to vaccination was weaker as compared to children with a birth weight >2000 g (P
      < 0.05). In systematic mass vaccination programmes, monitoring of antibody levels
      is not recommended unless the patient is at risk. However, in extremely preterm
      infants (< 1000 g at birth), especially after very serious infections, monitoring
      the level of anti-HBs antibodies after complete immunisation should be
      considered. In preterm infants who show very low postvaccination levels of anti
      HBs antibodies, stimulation with an additional double booster dose of vaccine
      gives positive results. CONCLUSION: The majority of preterm infants (98.4%)
      responded well to hepatitis B vaccination given at intervals of 0, 1, 2 and 12
      months and developed a protective level of antibodies. The level of anti
      hepatitis B surface antigen antibodies in children with a birth weight >2000 g
      was higher than in those with a birth weight < or = 1000 g.

PMID- 10206127
TI  - Isolated sphenoidal sinusitis in children.
AB  - Acute isolated infectious sphenoiditis is an uncommon, potentially dangerous
      condition which is often misdiagnosed because of its nonspecific symptoms and
      paucity of clinical signs. We present eight children with isolated sphenoiditis
      who were managed in our medical centre during the last 2 years and review the
      literature. All the patients were adolescents or pre-adolescents and all
      experienced moderate to severe refractory oppressive headache. Four had a history
      of sinusitis or allergic rhinitis. None had fever or any other directing clinical
      sign. Diagnosis was made by cranial computer tomography. All were treated with
      antibiotics and recovered completely without infectious or neurological
      complications. CONCLUSION: Acute isolated infectious sphenoiditis should be
      considered in adolescents and pre-adolescents who present with constant moderate
      to severe oppressive headache. Awareness of this entity will enable early
      diagnosis and initiation of antibiotic treatment which is essential to avoid
      complications and surgical intervention.

PMID- 10206128
TI  - Clinical relevance of monosomy 22q11.2 in children with pulmonary atresia and
      ventricular septal defect.
AB  - The purpose of our study was to describe the prevalence and the clinical spectrum
      of monosomy 22q11.2 in a population of patients with pulmonary atresia and
      ventricular septal defect. We examined all 44 patients with this conotruncal
      cardiac malformation who presented to our institution from January 1994 until
      December 1997. The type of collateral lung perfusion was recorded including
      anomalies of the pulmonary arteries as well as facial and immunological
      abnormalities. Molecular-cytogenetic testing for a 22q11.2 microdeletion was
      performed using the probes D22S75 and cHKAD26. Statistical differences were
      evaluated with the Fisher's Exact Test. Monosomy 22q11.2 was present in ten
      children (23%) with major aortopulmonary collateral arteries (group 1). The
      remaining 13 children (29%) with major aortopulmonary collateral arteries (group
      2) and all 21 children (48%) with ductus arteriosus (group 3) were negative for
      this microdeletion. All children in group 1 had facial anomalies, six had mild
      immunological abnormalities including decreased CD 4 + or CD 8 + cells. Anomalies
      of the pulmonary vascular bed were significantly more frequent in children of
      group 1 (9/10) than in children of group 2 (4/13) or group 3 (0/21). Due to these
      pulmonary vascular anomalies, corrective surgery had been accomplished in fewer
      children with monosomy 22q11.2 (none in group 1) as compared to 7/13 children in
      group 2 and 14/21 children in group 3. CONCLUSION: In children with pulmonary
      atresia and ventricular septal defect, monosomy 22q11.2 is preferentially
      associated with major aortopulmonary collateral arteries. Due to the higher
      incidence of pulmonary arterial abnormalities, successful surgical repair will
      require a different therapeutic approach in most patients with this
      microdeletion.

PMID- 10206129
TI  - Mesomelic dysplasia with periosteal thickening, radio-humeral dislocation,
      osteoporosis and multiple fractures.
AB  - We report a boy with a new form of mesomelic dysplasia characterised by short
      stature, multifocal periosteal thickening, radio-humeral dislocation,
      osteoporosis and multiple fractures with minimal trauma. Electrophoresis of
      fibroblast collagens detected defects in type III and type V collagen.
      CONCLUSION: Bone dysplasias presenting with osteopenia, abnormal trabecular
      pattern, bone fragility, and periosteal thickening suggest a collagenopathy. A
      possible collagen defect requires biochemical investigations.

PMID- 10206130
TI  - Neonatal suppurative parotitis: a study of five cases.
AB  - Suppurative parotitis is uncommon in newborns. During a 9-year study period, five
      cases of neonatal suppurative parotitis were detected in 3,624 hospital
      admissions. The relative risk of developing neonatal suppurative parotitis in
      admitted infants was 5.52 (0.62-49.35). Staphylococcus aureus was the causative
      organism most commonly detected in the hospital-acquired cases. Antimicrobial
      therapy was effective in all cases; surgery was not required. CONCLUSION:
      Although neonatal suppurative parotitis is now uncommon in the newborn, it cannot
      be considered a "vanishing disease".

PMID- 10206131
TI  - Is gastric lavage needed in neonates with meconium-stained amniotic fluid?
AB  - We compared the incidence of complications from meconium-containing gastric fluid
      in a group of neonates born with meconium-stained amniotic fluid (MSAF) who did
      not routinely have gastric lavage prior to feeds, versus a group who had elective
      gastric lavage before the first feed. In the first group, 275 neonates born with
      MSAF were fed without prior gastric lavage. While 13 developed feeding problems,
      the other 262 infants (95%) who did not undergo routine gastric lavage remained
      free of later feeding difficulties or secondary meconium aspiration. In the
      second group, all 227 neonates with MSAF had elective gastric lavage performed
      after birth. All remained free of later feeding difficulties or secondary
      meconium aspiration. CONCLUSION: Our data suggest that gastric lavage is not
      necessary in most neonates born with meconium-stained amniotic fluid, regardless
      of the thickness of the meconium-stained fluid, as no complications from meconium
      containing gastric fluid were observed.

PMID- 10206132
TI  - Early versus late dexamethasone treatment in preterm infants at risk for chronic
      lung disease: a randomized pilot study.
AB  - Abstract The purpose of this controlled, prospective pilot study was to compare
      the short-and long-term efficacy of early versus late treatment with
      dexamethasone (Dex) in preterm infants at risk for chronic lung disease (CLD).
      Thirty ventilated premature infants with a birth weight < or = 1250 g were
      randomized to receive Dex either from day 7 or from day 14. Dex was administered
      over 16 days tapering from 0.5 mg/kg per day to 0.1 mg/kg per day. The infants of
      the early treatment group could be weaned significantly earlier from the
      ventilator after 14 days (median; range 9-24) versus 24 days (median; range 8-44)
      in the late treatment group. The need for supplemental oxygen was shorter if Dex
      was started early - 24 days (median; range 10-57) versus 40 days (median; range
      10-74). Oxygen dependency at 28 days of age was similar between the groups 6 out
      of 14 infants (42.9%) versus 10 out of 16 patients (62.5%). The long-term
      efficacy of the two Dex regimens on lung function was evaluated by body
      plethysmographic measurements made at the age of 3 months. Thoracic gas volume
      and airway resistance were measured and specific airway conductance calculated.
      No statistically significant differences between the groups were demonstrated.
      CONCLUSION: Early dexamethasone treatment led to earlier extubation in our study
      population, but was not associated with significant advantages regarding oxygen
      dependency at 28 days of life and pulmonary function test at 3 months of age.

PMID- 10206133
TI  - Haemodynamic consequences of phototherapy in term infants.
AB  - The effect of blue-light phototherapy on cardiac output and brain and kidney
      perfusion was studied in 12 term infants with pulsed Doppler ultrasound. Mean (+/
      SD) gestational age and birth weight were 39.0 (+/-1.6) weeks and 3438 (+/-533) g
      respectively. Mean (+/-SD) age of the infants at which phototherapy was initiated
      was 3.5 (+/-0.8) days. Left ventricular output (LVO), mean left pulmonary artery
      blood flow (LPA), mean blood flow velocities of the internal carotid (CBFV) and
      renal (RBFV) arteries were studied in all infants prior to the onset of
      phototherapy, 30 min, 2 h, and 12 h after initiation of phototherapy, and before
      and 12-24 h after discontinuation of phototherapy. LVO decreased immediately
      after the onset of phototherapy. However, after 12 h, LVO returned to pre
      phototherapy values. LPA increased significantly after 12 h of exposure. LPA
      returned to pre-phototherapy values after discontinuation of phototherapy. CBFV
      increased, whereas RBFV decreased significantly after 2 h of exposure. After
      discontinuation of phototherapy CBFV as well as RBFV values returned to pre
      phototherapy values. CONCLUSION: Phototherapy does affect cardiac output and
      organ blood flow velocity in term infants. After termination of phototherapy the
      effect of phototherapy disappears.

PMID- 10206134
TI  - Adverse effects and sero-responses to an acellular pertussis/diphtheria/tetanus
      vaccine when combined with Haemophilus influenzae type b vaccine in an
      accelerated schedule.
AB  - Acellular pertussis vaccines provide protection against pertussis with few
      adverse effects. Differences in the reactogenicity and immunogenicity of
      available pertussis vaccines may be influenced by the immunisation schedule
      employed. We assessed responses to an acellular pertussis, diphtheria, tetanus
      vaccine mixed with Haemophilus influenzae type b (Hib) vaccine, (PRP-T) given at
      age 2, 3 and 4 months. Parents kept a symptom diary for 3 days after each
      immunisation. Antibodies to diphtheria, tetanus, pertussis toxin and filamentous
      haemagglutinin were measured by enzyme immunoassay at 2 and 5 months. Results
      were compared with historical controls who received a combination whole-cell
      pertussis, diphtheria, tetanus/PRP-T vaccine in the same schedule. A total of 262
      infants were recruited, of whom 251 were fully evaluated after three doses of
      vaccine. Systemic and most local reactions were less frequent following the
      acellular combination. Fever > or = 38 degrees C was reported after only 0.6% of
      doses. Redness or swelling > or = 2.5 cm were unusual after the first two doses
      (2-5%), but rates rose to 13% after the third dose. Antibody responses to
      diphtheria and tetanus toxoids were lower, while those to pertussis antigens were
      higher, more uniform and less attenuated by pre-immunisation antibody than in
      infants who received the whole-cell combination. All infants achieved protective
      antibody titres of at least 0.1 IU/ml for diphtheria and 0.01 IU/ml for tetanus.
      CONCLUSION: The acellular combination vaccine was immunogenic for diphtheria,
      tetanus and pertussis components and was associated with low rates of fever
      following immunisation.

PMID- 10206135
TI  - A girl with constipation and acute urinary retention.

PMID- 10206136
TI  - Fecal immunoreactive lipase, a simple diagnostic test for cystic fibrosis.

PMID- 10206137
TI  - A pilot study of growth hormone therapy in dilated cardiomyopathy.

PMID- 10206138
TI  - Guillain-Barre syndrome following serological evidence of hepatitis A in a child.

PMID- 10206139
TI  - Renovascular hypertension and prolonged encephalopathy associated with moyamoya
      disease.

PMID- 10206140
TI  - Transfusion-associated graft-versus-host disease following exchange transfusion
      in a newborn.

PMID- 10206141
TI  - Interferon alpha-2a therapy in haemangiomas of infancy: spastic diplegia as a
      severe complication.

PMID- 10206142
TI  - Resuscitation of the newly born infant: an advisory statement from the Pediatric
      Working Group of the International Liaison Committee on Resuscitation.
AB  - The International Liaison Committee on Resuscitation (ILCOR), with representation
      from North America, Europe, Australia, New Zealand, Africa, and South America,
      was formed in 1992 to provide a forum for liaison between resuscitation
      organizations in the developed world. This consensus document on resuscitation
      extends previously published ILCOR advisory statements on resuscitation to
      address the unique and changing physiology of the newly born infant within the
      first few hours following birth and the techniques for providing advanced life
      support.

PMID- 10206143
TI  - Herpesvirus saimiri strategies for T cell stimulation and transformation.

PMID- 10206144
TI  - Different manifestations of Toxoplasma gondii infection in F344 and LEW rats.
AB  - There is evidence that not only the immune status, but also the genetic
      predisposition of certain hosts influence the clinical outcome of Toxoplasma
      gondii infection. By far the majority of our knowledge on genetic and
      immunological mechanisms involved in control of T. gondii infection has been
      obtained by studying mouse models, which in terms of clinical outcome of
      infection differ considerably from humans. Rats which show a rather similar
      course of infection in comparison to humans have not so far been investigated for
      effects of genetic differences on course of the infection. In this study we show
      that, like mice, different strains of rats exhibit a remarkable variation in the
      number of brain cysts arising from chronic infection. LEW rats seem to be highly
      resistant to cyst formation, in contrast to F344 rats that are susceptible. In
      addition, F344 rats express high numbers of gammadelta T cells during the acute
      phase of infection, whereas LEW rats express elevated but comparably low numbers
      of gammadelta T cells. The RT1 (rat MHC) haplotypes of both strains are identical
      in the RT1A and RT1B/D regions, which encode the restriction elements for
      conventional peptide antigens. Consequently, rat strain-specific differences may
      be useful to define MHC-independent mechanisms of resistance against T. gondii,
      which may also act in humans.

PMID- 10206145
TI  - Inducible anti-parasitic effector mechanisms in human uroepithelial cells:
      tryptophan degradation vs. NO production.
AB  - In murine cells the most important effector mechanism directed against the
      intracellular pathogen Toxoplasma gondii is the production of toxic nitrogen
      oxides. In contrast the induction of the tryptophan degrading enzyme indolamine
      2,3-dioxygenase (IDO) has been described to be the most effective anti-parasitic
      mechanism in most human cells. In this report we analysed IDO induction and NO
      production in the human uroepithelial carcinoma cell line RT4. We found that
      after stimulation with IFN-gamma these cells were able to restrict toxoplasma
      growth. This was due to an activation of IDO, and the anti-parasitic effect
      mediated by RT4 cells was abrogated by the addition of L-tryptophan. In addition
      we found that the costimulation of RT4 cells with IL-1 and IFN-gamma results in
      the production of nitric oxide, and that in RT4 cells stimulated with both these
      cytokines, IDO activity and toxoplasmostasis was lower than in cells stimulated
      with IFN-gamma alone. This IL-1-mediated inhibition of IFN-gamma-induced IDO
      activity and toxoplasmostasis could be blocked by monomethyl L-arginine, an
      inhibitor of NO production. We therefore conclude that the induction of
      indolamine 2,3-dioxygenase activity in human cells is a very important effector
      mechanism directed against Toxoplasma gondii, and that in human cells the
      production of NO might be involved in the regulation of IDO activity.

PMID- 10206146
TI  - Reduced bacterial dissemination and liver injury in CD14-deficient mice following
      a chronic abscess-forming peritonitis induced by Bacteroides fragilis.
AB  - The CD14 myelomonocytic differentiation antigen plays a major role in acute Gram
      negative infections with Escherichia coli; however, its role in chronic
      infections has not yet been analyzed. To address this question, we studied the
      role of CD14 in a chronic abscess-forming peritonitis, induced by Bacteroides
      fragilis. B. fragilis (3x10(8) CFU/ml) were resuspended in a liquid nutrient agar
      and injected into the peritoneal cavity of CD14-deficient (CD 14-/-) and normal
      C57BL/6J (CD 14+/+) mice, respectively. After 3 days there was a severe
      phlegmonous intra-abdominal inflammation in both groups. After 7 days an abscess
      forming peritonitis developed and by 14 days the infectious foci were
      compartimentalized. These observations were indistinguishable between CD14-/- and
      CD14+/+ mice. Although no differences were seen in abscess formation, CD14-/-
      mice were able to clear B. fragilis more efficiently from the blood than CD14+/+
      mice. After 3, 7, and 14 days blood cultures were B. fragilis positive in 11%
      (1/9), 20% (2/10), and 0% (0/9) in CD14-/-compared with 90% (9/10), 78% (7/9),
      and 20% (2/10) in CD14+/+ mice, respectively (P<0.05). Furthermore, although the
      infection resulted in hepatocellular necrosis and severe hepatitis in both
      groups, at day 14 the liver cell damage was more severe in CD14+/+ than in CD14-/
      mice (P<0.05). These results show that the chronic abscess formation induced by
      B. fragilis capsular polysaccharides is CD14 independent; however, bacterial
      clearance and/or dissemination and liver cell damage are at least partially
      influenced by CD14-dependent mechanisms.

PMID- 10206147
TI  - Effect of cytokines on invasion and survival of Yersinia in primary human
      fibroblasts.
AB  - Bacteria or bacterial antigen triggering reactive arthritis have been detected in
      inflamed joint tissue and fluid of patients. Although live yersiniae have not yet
      been found in joints of patients with Yersinia arthritis, early dissemination and
      propagation has been proposed. In this study, we investigated the influence of
      the proinflammatory cytokines interleukin- (IL-) 1beta, tumor necrosis factor
      (TNF-) alpha, the Th1 lymphokine interferon- (IFN-) gamma, and the Th2 lymphokine
      IL-4 on the intracellular survival of Yersinia enterocolitica O.3 in primary
      human fibroblast cell monolayers as a model for joint tissue. Bacterial titers in
      infected cells decreased significantly and in a dose-dependent manner following
      treatment with IL-1beta, TNF-alpha, or IFN-gamma. The bactericidal effects of IL
      1beta and TNF-alpha were synergistic. In contrast, IL-4 significantly supported
      bacterial survival. In addition, IL-4 antagonized in part the bactericidal effect
      of TNF-alpha and IFN-gamma. Although IL-1beta, TNF-alpha, and IFN-gamma
      accelerated killing of intracellular yersiniae the ratio of cells containing
      bacterial antigen did not differ from that in untreated cells. The differential
      effects of the investigated cytokines on intracellular survival of yersiniae may
      be of relevance for the development of Yersinia arthritis: enhanced production of
      IL-4 by synovial tissue may prolong the survival of yersiniae and persistence of
      antigen, and thus potentiate immune complex formation and inflammation. In
      conclusion these results show (1) that fibroblasts can take up virulent yersiniae
      as non-professional phagocytes and (2) that cytokines, found in the joints of
      patients with Yersinia arthritis, are able to affect the intracellular survival
      of yersiniae differentially.

PMID- 10206148
TI  - Bioactive fragment of human interleukin-1beta (163-171) modulates the immune
      response to synthetic peptides of RESA of Plasmodium falciparum.
AB  - In this study a bioactive fragment, residues 163-171 of human interleukin-1beta
      (hu IL-1beta), that mimics the functions of the whole IL-1 molecule was
      chemically linked to two peptide sequences of the ring erythrocyte surface
      antigen (RESA), an asexual blood stage antigen of Plasmodium falciparum. The
      immunogenicity of different formulations was studied in different haplotypes of
      inbred mice. The peptide-IL-1beta conjugates delivered in liposomes showed the
      maximal antibody production. Antigen entrapped in liposomes at a dose of 5 microg
      showed antibody levels comparable to that of peptide conjugate in alum. The IgG
      subclass profile with different RESA peptides and its conjugates at various doses
      in liposomes induced predominantly IgG2a/2b isotypes while alum-delivered
      formulations showed both IgG1 and IgG2a/2b isotypes. In vitro studies of
      merozoite reinvasion showed varying degree (50-85%) of inhibition, maximum being
      with the peptide conjugates in liposomes (80-87%). Thus, this approach suggests
      that linking of hu IL-1beta is instrumental in augmenting the immune response
      against otherwise poorly immunogenic synthetic peptides.

PMID- 10206149
TI  - Layered murein revisited: a fundamentally new concept of bacterial cell wall
      structure, biogenesis and function.
AB  - The classical concept of the architecture of microbial murein assumes cross
      linked glycan chains to be arranged in horizontal layers outside of the plasma
      membrane. It necessitates elaborate hypotheses to explain processes such as the
      biosynthesis, growth and division of the bacterial cell wall and provides no
      explanation for transenvelope macromolecular transport. Moreover, this model is
      difficult to reconcile with a number of basic chemical and electron microscopical
      data. According to a fundamentally distinct concept which is presented here,
      glycan strands in the microbial wall run perpendicular to the plasma membrane,
      each strand being cross-linked by peptide bridges with four other strands. This
      arrangement allows the formation of a structured matrix pierced with ordered
      ionophoric channels potentially harboring either lipoprotein or teichoic
      (lipoteichoic) acid molecules in Gram-negative and Gram-positive bacteria,
      respectively. New wall structures are synthesized in toto emerging from the
      cytoplasmic membrane as a condensed gel-like network below the old wall without
      being covalently attached to it, expanding due to inherent elasticity as the old
      wall is lyzed. This model reflects published genetic and biochemical data and
      offers a simple explanation for peptidoglycan biogenesis. As the biosynthesis is
      terminated by enzymic cleavage of all glycan strands, murein is irreversibly
      released from the membrane. The murein detachment prepares the membrane for de
      novo assembly of both the new wall synthesis machinery and the multicomponent
      factory for protein, DNA and phospholipid transfer. Being assembled in parallel,
      both new murein and the traffic complexes grow from the membrane together. This
      concept eliminates the necessity for the traffic complexes to penetrate intact
      murein. In the process of simultaneous assembly, the expanding murein functions
      as a lifting platform driven by the force of turgor pressure, transporting
      macromolecules through the perisplasmic space.

PMID- 10206150
TI  - Investigations of the pathway of incorporation and function of lamin A in the
      nuclear lamina.
AB  - Cell-free extracts of Xenopus eggs were used to investigate how differing lamin
      sub-types are incorporated into a lamina and how lamina composition influences
      DNA replication. Purified recombinant human lamin A (HlaminA) was inoculated into
      egg extracts, which support in vitro nuclear assembly. The route of incorporation
      of Hlamin A into the lamina was compared to Xenopus lamin B3 (XlaminB3), the
      major endogenous lamin sub-type in egg extracts. While Xlamin B3 was incorporated
      into the lamina directly, HlaminA first accumulated at nucleoplasmic foci, before
      entering the lamina. When HlaminA was inoculated into extracts depleted of
      XlaminB3 it entered nuclei efficiently and was incorporated into nucleoplasmic
      foci. However, in the absence of XlaminB3, HlaminA remained in the foci and did
      not enter the nuclear envelope. When HlaminA entered the nuclear envelope, it did
      not influence DNA replication. Nuclei containing HlaminA initiated DNA
      replication on queue and in addition the spatial distribution of replication
      centres in these nuclei was identical to controls. Taken together, these results
      suggest that the incorporation of A-type lamins into the nuclear envelope is
      dependent upon the presence of B-type lamins. However, the presence of A-type
      lamins alone is not sufficient to influence the spatial and temporal order of DNA
      replication.

PMID- 10206151
TI  - In vitro binding of free cdc2 and raf kinase to membrane vesicles: a possible new
      regulatory mechanism for cdc2 kinase activation in Xenopus oocyte.
AB  - The G2-M transition of the cell cycle is under the control of the M-phase
      promoting factor (MPF) formed of cdc2 kinase and cyclin B. The Xenopus prophase
      blocked oocyte contains a stockpile of cyclin B2-cdc2 complexes that are
      maintained inactive by a double inhibitory phosphorylation on Thr-14 and Tyr-15
      of cdc2. Free cdc2 molecules that are not associated with cyclin, are present in
      excess as compared to cyclin B2-associated cdc2. This pool of free cdc2 is
      permanently recruited to associate with neosynthetized cyclin B2 in the resting
      prophase oocyte, to feed up the pre-MPF stockpile. During re-entry into meiosis,
      free cdc2 could generate with newly synthesized cyclin B a small level of active
      MPF, that could serve as starter to initiate the conversion of pre-MPF into MPF.
      It was, therefore, of high interest to investigate whether free cdc2 interacts
      with other proteins and what could be its intracellular localization. To address
      these questions, we developed an in vitro system of membrane vesicles. We
      demonstrate here that free cdc2 is recovered in association with the external
      layer of membrane vesicles, whereas cyclin B2-associated cdc2 is not. Cyclin is
      able to associate in vitro with cdc2-containing membrane vesicles. This
      association does not induce the inhibitory cdc2 phosphorylations. However, it
      does not lead to active complexes, suggesting that membrane vesicles prevent cdc2
      activation. C-Raf1, another kinase activated during reentry into meiosis, is also
      totally recovered in association with the membrane vesicles.

PMID- 10206152
TI  - Cell cycle analysis and synchronization of the Xenopus laevis XL2 cell line:
      study of the kinesin related protein XlEg5.
AB  - Cell free extracts prepared from Xenopus eggs are one of the most powerful in
      vitro systems to analyze cell cycle-regulated mechanisms such as DNA replication,
      nuclear assembly, chromosome condensation, or spindle formation. Xenopus embryos
      can complete several synchronous cell cycles in the absence of transcription,
      consequently Xenopus extracts are very helpful to study the molecular level of
      cellular mechanisms. Many key cell cycle regulators like p34cdc2 and cdk2 have
      been discovered and characterized using those extracts, but their regulation
      during somatic cell cycles have only been studied in mammalian cultured cells. In
      this paper, we describe optimized conditions to obtain cell cycle arrested
      Xenopus XL2 cultured cells. Synchronization of XL2 cells at different stages of
      the cell cycle was achieved by serum starvation and drug treatments such as
      aphidicolin, nocodazole, and ALLN. The degree of synchronization was assessed by
      indirect fluorescence microscopy and FACS analysis. This method was used to study
      the cell cycle expression of the Xenopus kinesin-related protein, XlEg5, a
      microtubule-based motor protein involved in movement and cell division in early
      development. We found that the expression of the protein was maximum in mitosis
      and minimum in G1, which correlated with the expression of its messenger RNA. XL2
      cultured cells were also used to analyze the ultrastructural sub-cellular
      localization of XlEg5. During mitosis, the protein was found around the
      centrosome in prophase, on the spindle microtubules in metaphase, and,
      interestingly, around the minus end of the midbody microtubules in telophase.

PMID- 10206153
TI  - Plakophilin, armadillo repeats, and nuclear localization.
AB  - Plakophilins are armadillo-repeat containing proteins, identified through their
      localization to desmosomes. Expressed in a wide range of tissues, plakophilins
      are largely nuclear in most cell types [Schmidt et al. (1997) Cell Tissue Res
      290:481; Mertens et al. (1996) J. Cell Biol 135:1009]. Using Xenopus embryos and
      cultured A6 cells, together with myc- and green fluorescent protein (GFP)-tags,
      we found that both the N-terminal, non-armadillo repeat "head" and the C-terminal
      armadillo repeat-containing regions can enter nuclei. The "arm" repeat domain is
      predominantly cytoplasmic and concentrated at the cell cortex, whereas the head
      and full-length polypeptides are concentrated in the nucleus. The head domain can
      also be seen to decorate and disrupt keratin filament network organization in
      some cells. In the course of these studies, we found that the distribution of the
      myc-epitope and green fluorescence differed in fixed cells, e.g., while the green
      fluorescence of a myc- and GFP-tagged head domain polypeptide was usually
      exclusively nuclear, a substantial fraction of the myc-immunoreactivity was
      cytoplasmic. Treating cells with the translation inhibitor cycloheximide reduces
      the cytoplasmic myc-signal, suggesting that it represented nascent polypeptides
      awaiting folding and nuclear import. Based on these types of experiments, GFP can
      be seen as a marker of the distribution of the mature form of the tagged
      polypeptide.

PMID- 10206154
TI  - Product review: lucis image processing software.
AB  - Lucis is a software program that allows the manipulation of images through the
      process of selective contrast pattern emphasis. Using an image-processing
      algorithm called Differential Hysteresis Processing (DHP), Lucis extracts and
      highlights patterns based on variations in image intensity (luminance). The
      result is that details can be seen that would otherwise be hidden in deep shadow
      or excessive brightness. The software is contained on a single floppy disk, is
      easy to install on a PC, simple to use, and runs on Windows 95, Windows 98, and
      Windows NT operating systems. The cost is $8,500 for a license, but is estimated
      to save a great deal of money in photographic materials, time, and labor that
      would have otherwise been spent in the darkroom. Superb images are easily
      obtained from unstained (no lead or uranium) sections, and stored image files
      sent to laser printers are of publication quality. The software can be used not
      only for all types of microscopy, including color fluorescence light microscopy,
      biological and materials science electron microscopy (TEM and SEM), but will be
      beneficial in medicine, such as X-ray films (pending approval by the FDA), and in
      the arts.

PMID- 10206155
TI  - The specialty of neuroimaging in neurology: a counter-revolution in Europe?

PMID- 10206156
TI  - MRI characteristics of midbrain tumours.
AB  - We diagnosed 60 cases of midbrain tumours by MRI between 1993 to 1997. There were
      39 males and 21 females, aged 2-64 years, mean 25.6 years. We found 38 patients
      with true intramedullary mid-brain tumours, 11 predominantly in the tectum, 20 in
      the tegmentum and 7 with a downward extension to the pons; there were 7 within
      the cerebral aqueduct. There were 22 patients with infiltrating midbrain tumours
      extending from adjacent structures, 11 cases each from the thalamus and pineal
      region. All patients received surgical treatment. Gross total resection was
      achieved in 42 cases, subtotal (> 75 %) resection in 18. Pathological diagnoses
      included 16 low-grade and 15 high-grade astrocytomas; 5 oligodendroastrocytomas;
      2 ependymomas; 11 glioblastomas; and 11 pineal parenchymal or germ-cell tumours.
      Midbrain tumours are a heterogeneous group of neoplasms, with wide variation in
      clinical and MRI features, related to the site and type of tumour. MRI not only
      allows precise analysis of their growth pattern, but also can lead to a correct
      preoperative diagnosis in the majority of cases.

PMID- 10206157
TI  - Single-shot echo-planar imaging of multiple sclerosis: effects of varying echo
      time.
AB  - Our aim was to determine the relative merits of short and long echo times (TE)
      with single-shot echo-planar imaging for imaging cerebral lesions such as
      multiple sclerosis. We examined seven patients with clinically definite multiple
      sclerosis were imaged at 1.5 T. Patients were scanned with spinecho, single-shot
      echo-planar imaging, using TEs of 45, 75, 105, and 135 ms. Region of interest
      (ROI) measurements were performed on 36 lesions at or above the level of the
      corona radiata. The mean image contrast (IC) was highest (231.1) for a TE of 45
      ms, followed by 75 ms (218.9), 105 ms (217.9), and 135 ms (191.6). When mean
      contrast-to-noise ratios (C/N) were compared, the value was again highest (29.7)
      for TE 45 ms, followed by 75 ms (28.9), 105 ms (28.5), and 135 ms (26.3). In a
      lesion-by-lesion comparison, TE 45 ms had the highest IC and C/N in the largest
      number of cases (50 % and 47.2 %, respectively). IC and C/N for TE 45 ms were
      superior to those of 75 ms in 64% and 58%, respectively. These results support
      the use of relatively short TEs for single-shot echo-planar imaging in the
      setting of cerebral lesions such as multiple sclerosis.

PMID- 10206158
TI  - Intrapituitary fluid levels following haemorrhage: MRI appearances in 13 cases.
AB  - Demonstration of fluid levels on MRI is well recognised in cerebral haematomas,
      tumours and cysts. The occurrence of fluid levels within haemorrhagic pituitary
      tumours has not previously been described in detail. Evidence of haemorrhage was
      identified in 27 of 125 pituitary tumours. Fluid levels occurred in 13 of these
      haemorrhagic tumours. No association with histological type was identified.
      Recognised risk factors for haemorrhage were identified in half of the cases.

PMID- 10206159
TI  - Role of diffusion-weighted echo-planar MRI in distinguishing between brain brain
      abscess and tumour: a preliminary report.
AB  - Our purpose was to evaluate diffusion-weighted (DW) echo-planar MRI in
      differentiating between brain abscess and tumour. We examined two patients with
      surgically confirmed pyogenic brain abscess and 18 with metastatic brain tumours
      or high-grade glioma, using a 1.5 T system. The apparent diffusion coefficient
      (ADC) of each necrotic or solid contrast-enhancing lesion was measured with two
      different b values (20 and 1200 s/mm2). All capsule-stage brain abscesses (4
      lesions) and zones of cerebritis (2 lesions) were identified on high-b-value DWI
      as markedly high-signal areas of decreased ADC (range, 0.58-0.70 [(10-3 mm2/s;
      mean, 0.63)]). All cystic or necrotic portions of brain tumours (14 lesions) were
      identified on high-b-value DWI as low-signal areas of increased ADC (range, 2.20
      3.20 [(10-3 mm2/s; mean, 2.70)]). Solid, contrast-enhancing portions of brain
      tumours (19 lesions) were identified on high-b-value DWI as high-signal areas of
      sightly decreased or increased ADC (range, 0.77-1.29 [(10-3 mm2/s; mean, 0.94)]).
      Our preliminary results indicate that DW echo-planar MRI be used for
      distinguishing between brain abscess and tumour.

PMID- 10206160
TI  - Hyperacute infarction: a comparison of CT and MRI, including diffusion-weighted
      imaging.
AB  - We compared CT and MRI obtained within the first 3 h of onset of a cerebral
      infarct. Echo-planar diffusion-weighted MRI delineated the infarcted areas most
      clearly, and subtle low-density areas on CT were consistent with those shown to
      be abnormal by diffusion-weighted MR. The signal changes of affected areas on
      fast spin-echo proton-density, T2-weighted and fast FLAIR images were subtler
      than the low density on CT.

PMID- 10206161
TI  - Isolated pontine infarction due to rhinocerebral mucormycosis.
AB  - We report a patient with rhinocerebral mucormycosis whose initial central nervous
      system involvement was isolated pontine infarction due to basilar arteritis
      caused by the fungus. The patient was diagnosed and followed by MRI and CT and
      basilar arteritis was demonstrated well on MRI studies. Involvement of the skull
      base was shown on CT in the later stage of the disease. The unusual initial
      presentation of the infection is discussed.

PMID- 10206162
TI  - MRI in an unusually protracted neuronopathic variant of acid sphingomyelinase
      deficiency.
AB  - MRI was performed in two siblings with the neuropathic sphingomyelinase
      deficiency caused by identical mixed heterozygosity in the structural acid
      sphingomyelinase gene. The clinical phenotype of the cases is unique in showing a
      rather protracted course, both having reached the fourth decade. Pronounced
      cerebellar and mild supratentorial atrophy was seen on MRI in both siblings, in
      contrast to their strikingly different clinical status. One has no overt
      neurological deficit, while the second had neocerebellar symptoms and signs,
      nystagmus and cranial nerve palsies for some years. The MRI findings, together
      with the cherry-red spot in the ocular fundus, ultrastructurally proved storage
      in cutaneous nerve Schwann cells and the histopathologically proven brain
      neuronal storage in a third sibling who died after a relatively rapid course
      dominated by fatal visceral storage, is evidence that a remarkably restricted
      neuropathology can be caused by this enzymopathy.

PMID- 10206163
TI  - Hypocaeruloplasminaemia with heteroallelic caeruloplasmin gene mutation: MRI of
      the brain.
AB  - We present two patients with hypocaeruloplasminaemia and a heteroallelic
      caeruloplasmin gene mutation (HypoCPGM). These patients had diabetes mellitus and
      tremor of the hands, respectively. T2-weighted fast spin-echo MRI showed mildly
      reduced intensity of the putamen, much more marked on echo-planar imaging.

PMID- 10206164
TI  - Changing characteristics of a colloid cyst of the third ventricle.
AB  - We describe extremely unusual radiological characteristics in a colloid cyst of
      the third ventricle, where the cyst became dense and its size decreased following
      a cerebrospinal fluid diversion procedure. Such a course of events has been
      reported in colloid cysts only twice in the literature.

PMID- 10206165
TI  - Rostral vermian cortical dysplasia: MRI.
AB  - The MRI findings in rostral vermian dysplasia are described for the first time.
      Defective foliation and abnormal fissuration of the rostral vermis can clearly be
      depicted on coronal images. The abnormalities are limited to the anterior lobe of
      the vermis and its hemisphere extension. A hypothesis is put forward to explain
      the abnormalities. It is suggested that the vermian changes result from an
      intrauterine insult at the end of the first trimester. There appears to be a
      variable degree of expression and associated cerebellar and cerebral cortical
      abnormalities can be seen. The clinical significance of these findings remains
      incompletely understood but may be related to the severity of the abnormalities.
      It is also suggested that a mild degree of vermian rostral dysplasia may
      represent an incidental imaging finding.

PMID- 10206166
TI  - High-intensity basal ganglia lesions on T1-weighted images in two toddlers with
      elevated blood manganese with portosystemic shunts.
AB  - We report two toddlers with portosystemic shunts who had symmetrical high-signal
      globus pallidus lesions on T1- but not T2-weighted MRI, and measurement of whole
      blood manganese at 2 years of age. These cases suggest that portosystemic shunts
      can cause elevation of blood manganese and result in manganese accumulation in
      the globus pallidus, causing high signal on T1-weighted images even in
      asymptomatic toddlers.

PMID- 10206167
TI  - Spontaneous remission of chiasmatic/hypothalamic masses in neurofibromatosis type
      1: report of two cases.
AB  - We report two children with neurofibromatosis type 1 showing enhancing masses on
      MRI suggesting neoplasms in the chiasm and hypothalamic region. In both patients
      no visual or endocrinal dysfunction was present. On serial MRI spontaneous
      partial remission was found, implying that a cautious approach to therapeutic
      management of similar cases should be taken.

PMID- 10206168
TI  - Melanotic neuroectodermal tumour of infancy at the anterior fontanelle.
AB  - We describe a 4-month-old girl presenting with a melanotic neuroectodermal tumour
      of infancy at the anterior fontanelle. According to the neuroimaging findings,
      this tumour was found to lie epidurally, adherent to the dura mater, with
      thickening of the adjacent frontal bone. The tumour was dense on CT, while MRI
      showed a major part of the tumour to be isointense with cerebral cortex on both
      T1- and T2-weighted images. The neuroimaging and clinical features are briefly
      discussed.

PMID- 10206169
TI  - Congenital varicella syndrome: cranial MRI in a long-term survivor.
AB  - Congenital varicella syndrome is a rare disorder which follows maternal infection
      in the first or early second trimester. The syndrome comprises a number of
      malformations including microcephaly, cortical destruction and limb hypoplasia.
      We describe a case where there has been long-term survival following second
      trimester maternal infection. The clinical findings, including the characteristic
      lower limb hypoplasia, are documented, as are the appearances on cranial MRI
      indicating an encephaloclastic porencephaly.

PMID- 10206170
TI  - High-resolution conjunctival contrast-enhanced MRI dacryocystography.
AB  - We assessed high-resolution MRI of the lacrimal system with conjunctival contrast
      enhancement in patients with suspected stenosis. We studied 18 patients with
      epiphora affecting 22 eyes, using a surface coil, before and after conjunctival
      and intravenous Gd-DTPA. Stenosis or obstruction of the ducts was found in 18 of
      22 cases: at canalicular level in 3 cases, at the sac in 7 cases, and in the
      nasolacrimal duct in 8 cases. Periductal pathology following surgery to the
      maxillary sinus or dacryocystorhinostomy was seen in three cases. In conjunction
      with the findings on syringing and/or conventional dacryocystography, the
      narrowing was classified as stenosis or obstruction.

PMID- 10206171
TI  - Intra-arterial vein bypass using a vein-loaded stent system to occlude wide
      necked aneurysms: an experimental study in dogs.
AB  - We treated 13 experimental wide-necked aneurysms of lateral type produced in dog
      carotid arteries with a vein-loaded stent system consisting of an autologous vein
      graft, a vein-carrier stent, and two other self-expanding Z-shaped stents. The
      vein-loaded stent, made by connecting the autologous vein graft to the vein
      carrier stent, was implanted in the common carotid artery to seal the aneurysm's
      orifice, after which two booster stents were deployed. The distal stent was
      placed to fix the distal end of the vein graft, and the proximal stent was placed
      at the proximal venous portion of the vein-loaded stent to reinforce its proximal
      end. In this manner an intra-arterial bypass was established across the aneurysm.
      Of 13 aneurysms seven were completely occluded, preserving the parent artery. The
      remaining six procedures resulted in parent artery occlusion because of failures
      in stent deployment. Angiograms performed in within 1 week six successfully
      treated dogs revealed the parent artery to be patent in four but thrombosed in
      two. Histological study of successful cases showed as smooth intima with slight
      endothelial hypertrophy and partially organised thrombus. The intraluminal
      features were also observed with a vascular endoscope at the time of treatment in
      four dogs and at the time of follow-up angiography in two. The appearances
      corresponded well to the macroscopic findings in the specimens. Our vein-loaded
      stent system offers complete closure of the orifice, which does not occur with
      conventional stent placement. The method is believed to show clinical promise for
      treating wide-necked aneurysms not curable by embolisation of the sac.

PMID- 10206172
TI  - Locomotion elicited by MK801 in developing and adult rats: temporal,
      environmental, and gender effects.
AB  - The effects of environmental novelty on locomotion elicited by an N-methyl-D
      aspartate (NMDA) receptor antagonist, (+)MK-801 hydrogen maleate [(5R,10S)-(+)-5
      methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine], were investigated.
      Male and female rats aged 10, 20, 30 or 54-68 days were injected s.c. with MK801
      and placed in activity monitors either immediately (no-delay) or after a 60 min
      delay (delay). In the no-delay condition, MK801 induced an inverse U-shaped dose
      response effect on locomotion; peak activation occurred with 0.1 mg/kg and ataxia
      occurred with higher doses. The introduction of a novel environment 60 min after
      drug injection shifted the dose-effect function of MK801 to the left; i.e., in
      rats 20 days of age and older, the activity induced by 0.1 mg/kg MK801 was
      potentiated in the delay condition. For the 0.5 mg/kg dose, 20-day-olds showed
      activation in the no-delay condition but ataxia in the delay condition. This dose
      induced ataxia followed by activation in 30-day-olds and adult males or ataxia in
      adult females, regardless of delay condition. Age-, gender-, and novelty
      dependent variations in MK801-induced locomotion may reflect differences in
      limbic-motor circuitry.

PMID- 10206173
TI  - Mecamylamine-precipitated nicotine-withdrawal aversion in Lewis and Fischer 344
      inbred rat strains.
AB  - Many studies have indicated that Lewis and Fischer 344 inbred rat strains show
      marked differences in behavioral responses to abused drugs. In the present study,
      we sought to determine whether these two strains of rats show different responses
      in mecamylamine-precipitated nicotine-withdrawal aversion using the conditioned
      place preference paradigm. Rats were treated subcutaneously with 10 mg/kg/day
      nicotine for 7 days using an osmotic minipump. After chronic nicotine infusion,
      the nicotinic receptor antagonist mecamylamine produced a significant place
      aversion in Lewis, but not in Fischer 344 rats. These results suggest that
      mecamylamine-precipitated nicotine-withdrawal aversion is strongly regulated by
      genetic factors.

PMID- 10206174
TI  - Role of metabotropic glutamate receptors in the hypersusceptibility to
      pentylenetetrazole-induced seizure during diazepam withdrawal.
AB  - To clarify the contribution of metabotropic glutamate (mGlu) receptors in brain
      to benzodiazepine withdrawal signs, we now examine the effects in mice of
      selective ligands for three subgroups of mGlu receptor on the hypersusceptibility
      to pentylenetetrazole-induced seizure during diazepam withdrawal. The seizure
      threshold for pentylenetetrazole was significantly decreased by the
      discontinuation of chronic diazepam treatment. The decrease in the seizure
      threshold for pentylenetetrazole during diazepam withdrawal was significantly
      suppressed by intracerebroventricular (i.c.v.) pretreatment with the group 1 mGlu
      receptor antagonist, (S)-4-carboxyphenylglycine ((S)-4CPG: 56 and 100 nmol).
      These doses of (S)-4CPG did not alter the seizure threshold in chronically
      vehicle-treated (control) mice. Pretreatment i.c.v. with a presynaptic mGlu
      receptor agonist (the group 2 mGlu receptor agonist (2S,1'S,2'S)-2
      (carboxycyclopropyl)-glycine (L-CCG-I: 3.0 and 5.6 nmol) and the group 3 mGlu
      receptor agonist, L-amino-4-phosphonobutyric acid (L-AP4: 3.0 and 5.6 nmol))
      failed to suppress the decrease in seizure threshold in diazepam-withdrawn mice,
      but increased the seizure threshold in control mice. Pretreatment i.c.v. with the
      group 1 mGlu receptor antagonist/group 2 mGlu receptor agonist, (S)-4-carboxy-3
      hydroxyphenylglycine ((S)-4C3HPG: 56 and 100 nmol), significantly increased the
      seizure threshold in control mice and suppressed the decrease in seizure
      threshold in diazepam-withdrawn mice. These findings suggest that enhancement of
      group 1 mGlu receptor function and a decline in both group 2 and group 3 mGlu
      receptor functions may play an important role in the hypersusceptibility to
      pentylenetetrazole-induced seizure during diazepam withdrawal.

PMID- 10206176
TI  - Group I mGlu receptor modulation of dopamine release in the rat striatum in vivo.
AB  - The present study investigated the ability of mGlu (metabotropic glutamate)
      receptor to modulate dopamine release in the striatum of freely moving rats
      assessed using the microdialysis technique. The group I and II mGlu receptor
      agonist (1S,3R)-ACPD (1-amino-cyclopentane-1,3-dicarboxylate; 1-3 mM) increased
      dopamine release (367% of basal levels) which was prevented by the non-selective
      mGlu receptor antagonist, (+)-MCPG (alpha-methyl-4-carboxyphenylglycine; 10 mM).
      The group I mGlu receptor agonist, DHPG (3,5-dihydroxyphenylglycine; 0.3-1 mM),
      also increased dopamine release (maximum increase 229%) which was also
      antagonised by (+)-MCPG (10 mM). In contrast, the group II mGlu receptor agonist,
      DCG-IV (2-(2,3-dicarboxycyclopropyl)glycine; 3-50 microM), induced a more modest
      increase in dopamine release (156% of basal levels). Combined administration of
      DHPG (1 mM) and DCG-IV (50 microM) maximally increased dopamine release by 252%
      of basal levels which was antagonised completely by (+)-MCPG (10 mM). Such
      findings indicate that group I (and possibly group II) mGlu receptors facilitate
      rat striatal dopamine release in vivo.

PMID- 10206175
TI  - Effects of increasing doses of vigabatrin on platelet gamma-aminobutyric acid
      transaminase and brain gamma-aminobutyric acid in rats.
AB  - We report the relationship of GABA-transaminase inhibition in platelets and brain
      with the increase in brain gamma-aminobutyric acid (GABA), as percents of the
      control, at 24 h after single and after 3 and 8 days of treatment with increasing
      doses (1, 3, 10, 30, 100 and 300 mg kg(-1) day(-1) of vigabatrin in rats. The
      inhibition of GABA-transaminase in platelets correlated at least as well as that
      in brain with the increase in brain GABA after 3 days (r = - 0.87 vs. r = -0.78),
      and 8 days of treatment (r = -0.77 vs. r = -0.74), and when the data of single
      and multiple doses were pooled (r = -0.77 vs. r = -0.75). The correlation between
      platelet GABA-transaminase and brain GABA fitted to a power curve, the increase
      in brain GABA being significant only when platelet GABA-transaminase was
      inhibited to less than 50% of the control. Our results suggest that platelet GABA
      transaminase could be a peripheral marker of the effect of vigabatrin on brain
      GABA in rats.

PMID- 10206177
TI  - Contribution of spinal mu1-opioid receptors to morphine-induced antinociception.
AB  - To determine the role of mu-opioid receptor subtypes, mu1 and mu2, in
      antinociception induced by intrathecal (i.t.) or intracerebroventricular (i.c.v.)
      injection of morphine, we assessed the effect of naloxonazine, a selective
      antagonist at mu1-opioid receptors. The antinociceptive effects of morphine were
      measured using four different nociceptive tests. The selective mu1 antagonist,
      naloxonazine (35 mg/kg, s.c.), 24 h before testing antagonized the
      antinociceptive effect of morphine on responses to chemical and thermal stimuli
      to a greater extent than that on responses to mechanical stimuli, as judged from
      ED50 values. The present results suggest that the antinociceptive activity of
      both i.t. and i.c.v. morphine on responses to chemical and thermal stimuli may be
      mediated through the mu1-opioid receptor subtype (naloxonazine-sensitive sites).
      These findings may be interpreted as indicative of the existence of mu1-receptor
      subtypes capable of mediating antinociception not only in supraspinal sites but
      also in spinal sites.

PMID- 10206178
TI  - The cardioprotective effects of nitroglycerin-induced preconditioning are
      mediated by calcitonin gene-related peptide.
AB  - Previous investigations have shown that endogenous calcitonin gene-related
      peptide (CGRP) may play an important role in the mediation of ischemic
      preconditioning and that nitroglycerin evokes the release of CGRP. In the present
      study, we examined whether nitroglycerin provides a preconditioning stimulus, and
      whether the cardioprotective effects of nitroglycerin-induced preconditioning
      involve endogenous CGRP. Thirty minutes of global ischemia and 30 min of
      reperfusion caused a significant impairment of cardiac contractile function and
      an increased release of creatine kinase. Pretreatment with nitroglycerin at the
      concentration of 3x10(-7) or 10(-6) M for 5 min produced a significant
      improvement of cardiac function and a decrease in the release of creatine kinase.
      The content of CGRP-like immunoreactivity in coronary effluent was increased
      during nitroglycerin perfusion. However, the cardioprotection afforded by
      nitroglycerin was abolished by CGRP-(8-37) (10(-7) M), a selective CGRP receptor
      antagonist. Pretreatment with capsaicin (50 mg/kg, s.c.), which specifically
      depletes the transmitter content of sensory nerves, also abolished the protective
      effects of nitroglycerin and markedly reduced the release of CGRP from the heart
      during nitroglycerin perfusion. These findings suggest that nitroglycerin-induced
      preconditioning is related to stimulation of CGRP release in rat hearts.

PMID- 10206179
TI  - Acute hemodynamic and renal effects of adrenomedullin in rats with aortocaval
      shunt.
AB  - Heart failure is characterized by increased vascular resistance and water
      retention. Adrenomedullin is a peptide hormone with vasodilating and diuretic
      properties whose efficacy in heart failure has not been well established. We used
      an aortocaval shunt model of moderate heart failure in rats and infused
      increasing doses of adrenomedullin, both as bolus injections and 20-min
      infusions. In controls, a clear dose-dependent 4.8+/-1.0 to 13.6+/-2.3 mm Hg
      decrease in arterial blood pressure was observed after injection of 1 microg to
      30 microg of adrenomedullin. In rats with aortocaval shunt, the hypotensive
      responses were significantly diminished. The urine flow rate, which was
      diminished at baseline in rats with aortocaval shunt, was increased and
      normalized by adrenomedullin administration. The glomerular filtration rate
      increased after infusion of adrenomedullin (0.5 microg/kg min(-1)) from 2.37+/
      0.25 to 3.47+/-0.43 ml/min (P<0.01) in controls and from 1.79+/-0.33 to 2.58+/
      0.49 (P<0.05) in rats with aortocaval shunt. Similarly, renal blood flow was
      significantly increased by adrenomedullin in both groups. Our results indicate a
      beneficial effect of adrenomedullin on renal function in rats with aortocaval
      shunt. These data suggest that adrenomedullin might be of potential therapeutic
      value in heart failure, without inordinately decreasing blood pressure.

PMID- 10206180
TI  - Effects of endothelin ET(B) receptor agonists and antagonists on the biphasic
      response in the ileum.
AB  - In the guinea-pig ileum, both sarafotoxin S6c and IRL1620 (Suc
      [Glu9,Ala11,15]endothelin-1-(8-21) induced a concentration-dependent biphasic
      effect (relaxation and contraction), but distinct tachyphylaxis of the tissue.
      Cross-tachyphylaxis and additivity experiments evidenced distinct receptors for
      these agonists. BQ-123 (cyclo[D-Trp-D-Asp-Pro-D-Val-Leu]), an endothelin ET(A)
      receptor antagonist, did not affect the response induced by either agonist.
      PD145065 [Ac-(D-Bhg-Leu-Asp-Ile-Ile-Trp) (D-Bhg = 5H-dibenzyl[a,d]cycloheptene
      10,11-dihydroglycine)], an endothelin ET(A)/ET(B) receptor antagonist, inhibited
      the contractions induced by IRL1620 and sarafotoxin S6c in competitive and
      noncompetitive manner, respectively. RES-701-1 [cyclic(Gly1-Asp9)(Gly-Asn-Trp-His
      Gly-Thr-Ala-Pro-Asp-Trp-P he-Phe-Asn-Tyr-Tyr-Trp)], an endothelin ET(B1) receptor
      antagonist, inhibited both components of the response induced by IRL1620, whereas
      it inhibited mainly the relaxation induced by low sarafotoxin S6c doses. Apamin
      and suramin had different effects towards the agonists. Our results suggest that
      two endothelin ET(B) receptors with distinct signal transduction mechanism
      mediate the biphasic response: (1) the endothelin ET(B1) receptor: sensitive to
      RES-701-1 and PD145065 and (2) the endothelin ET(B2) receptor: less sensitive to
      RES-701-1 and PD145065.

PMID- 10206181
TI  - Evidence that inhibitory neurotransmission differs between the proximal and
      distal segments of guinea-pig taenia caeci.
AB  - The effect of atropine (1 microM) and N(G)-nitro-L-arginine (L-NOARG, 10 microM)
      on electrical field stimulation induced relaxation in proximal and distal
      segments of guinea-pig taenia caeci in the presence of guanethidine (4 microM)
      was studied. The frequency-dependent relaxations were lower in proximal than in
      distal segments both in the presence and in the absence of atropine. The effect
      of L-NOARG (an inhibitor of nitric oxide (NO) synthase) on relaxation in the
      presence of atropine depended on the frequency of electrical stimulation and the
      segment used; the effect of L-NOARG was greater in proximal segments than in
      distal segments. In the absence of atropine, the inhibitory effect of L-NOARG was
      the same in both segments at all frequencies tested. This study demonstrates
      differences between the opposite extremes of guinea-pig taenia caeci in
      relaxations induced by electrical stimulation. Our data also show a role of NO
      that is dependent on the integrity of cholinergic transmission.

PMID- 10206182
TI  - Decreased sensory neuropeptide release from trachea of rats with streptozotocin
      induced diabetes.
AB  - We studied the release of somatostatin, calcitonin gene-related peptide (CGRP)
      and substance P in response to electrical field stimulation from isolated
      tracheas of rats following 4 weeks of streptozotocin (50 mg/kg i.v.)-induced
      diabetes. Field stimulation (40 V, 0.1 ms, 10 Hz for 120 s) increased the release
      of somatostatin, CGRP and substance P from the baseline 0.18+/-0.029, 0.17+/
      0.027, and 1.77+/-0.086 to 0.51+/-0.022, 0.69+/-0.115, and 5.96+/-0.377 in
      control preparations and 0.31+/-0.081, 0.41+/-0.142, and 3.14+/-0.443 fmol/mg wet
      tissue weight in preparations from diabetic rats as measured by radioimmunoassay
      (control vs. diabetic P<0.01 for each). The results show a simultaneous decrease
      in release of the three sensory neuropeptides and an enhanced plasma somatostatin
      level in rats with streptozotocin-induced diabetes.

PMID- 10206184
TI  - Activation of nuclear transcription factor kappaB in rat carrageenin-induced
      pleurisy.
AB  - In this study we investigated the activation of nuclear factor-kappaB in the
      carrageenin-induced rat pleurisy. We found that nuclear factor-kappaB DNA binding
      activity, measured in inflammatory cells which migrated into the pleural cavity,
      was detectable at 3 and 6 h, markedly increased at 24 h and decreased at 48 h
      after induction of the inflammation. The increase in nuclear factor-kappaB DNA
      binding activity paralleled both exudate formation and leukocyte infiltration.
      Treatment of animals with pyrrolidine dithiocarbamate, an inhibitor of nuclear
      factor-kappaB activation, inhibited the nuclear factor-kappaB DNA binding
      activity as well as exudate formation and leukocyte infiltration. These results
      indicate that nuclear factor-kappaB is activated in the carrageenin-induced
      pleurisy and suggest that its inhibition may represent a novel strategy for the
      modulation of inflammatory response.

PMID- 10206185
TI  - Endothelin-1 enhances vascular cell adhesion molecule-1 expression in tumor
      necrosis factor alpha-stimulated vascular endothelial cells.
AB  - Vascular cell adhesion molecule-1 (VCAM-1) is a mononuclear leukocyte-selective
      adhesion molecule that is expressed in human vascular endothelial cells at sites
      of local inflammation. It participates in local endothelial-monocyte interactions
      during the initiation of atherosclerosis. In the present study, endothelin alone
      did not induce the surface expression and mRNA accumulation of VCAM-1 in human
      vascular endothelial cells, but inhibition of endogenous nitric oxide (NO) by
      N(G)-monomethyl-L-arginine enhanced the surface expression and mRNA accumulation
      of VCAM-1 stimulated by endothelin-1. It is conceivable that in human vascular
      endothelial cells, stimulation of an endothelin receptor results in the
      production of nitric oxide (NO), suppressing the expression of VCAM-1. Endothelin
      1 enhanced the surface expression and mRNA accumulation of VCAM-1 in cells
      treated with tumor necrosis factor alpha (TNF-alpha). The enhancement by
      endothelin-1 may be explained by the inhibitory effect of TNF-alpha on endothelin
      induced NO production. Pretreatment with BQ788 (an endothelin ET(B) receptor
      antagonist) or inhibitors of nuclear factor kappa B (NF-kappaB) activation
      completely diminished the synergistic enhancement of VCAM-1 expression by
      endothelin-1 in TNF-alpha-stimulated vascular endothelial cells, both at the
      protein and mRNA levels. These findings suggest that the synergistic enhancement
      of VCAM-1 expression by TNF-alpha and endothelin ET(B) receptor stimulation may
      be augmented by the induction of NF-kappaB binding activity in human vascular
      endothelial cells.

PMID- 10206183
TI  - Comparative effects of a glucocorticosteroid, theophylline and the peptido
      leukotriene-antagonist CGP 45715A on antigen-induced early and late phase airway
      response and inflammatory cell influx in sensitised guinea pigs.
AB  - A novel model of allergic early and late-phase reaction in the airways of
      conscious guinea pigs was developed and the effect of established and novel
      antiasthmatic drugs on peak of immediate response, late phase response and
      associated inflammatory cell influx investigated. Guinea pigs were sensitised
      twice in adjuvant (50 mg/kg silica + 0.1 ml/kg Bordetella pertussis). Under cover
      of 10 mg/kg i.p. mepyramine guinea pigs exhibited still a pronounced immediate
      reaction. During a screening phase about 75% of guinea pigs demonstrated a late
      phase reaction of decrease of tidal volume between 4-10 h after ovalbumin
      inhalation. In a cross over study theophylline at 50 mg/kg p.o. (-1 h before
      ovalbumin) tended to attenuate not only the peak of the immediate reaction by
      about 69% (P>0.05, n = 12), but inhibited the airway late phase response
      significantly (P<0.05, 5-10 h, n = 12). Methylprednisolone (40 mg/kg p.o. 1 h
      before ovalbumin) did not inhibit the immediate response, but the late phase
      response. In contrast the cysteinyl-leukotriene antagonist CGP 45715A (Iralukast;
      30 mg/kg p.o. 2 h before ovalbumin) neither interfered with the peak of the
      immediate, nor with the late phase response. When bronchoalveolar lavage by
      orotracheal route was performed 24 h after ovalbumin inhalation, total cell
      count, eosinophils, neutrophils, macrophages and lymphocytes were significantly
      increased in ovalbumin-controls compared to sham (n = 5; P<0.05).
      Methylprednisolone reduced significantly the antigen-induced increase of total
      cell count and eosinophil number. Neither theophylline nor the cysteinyl
      leukotriene receptor antagonist attenuated the antigen-associated cell influx.
      The results do not provide evidence for a major role of cysteinyl-leukotrienes in
      the late phase response and inflammatory cell influx in this model.

PMID- 10206186
TI  - Ethanol sensitivity of NMDA receptor function in developing cerebellar granule
      neurons.
AB  - The mechanism by which ethanol inhibits the function of the NMDA subtype of
      glutamate receptor has not been elucidated. One possibility that has been
      suggested is that NMDA receptor subunit composition influences the sensitivity of
      the receptor to ethanol. We have taken advantage of developmental changes in
      subunit composition of the NMDA receptor in cultured neurons to examine possible
      changes in the effect of ethanol. We found an increase in expression of the NR2A
      subunit, and a decrease in expression of the NR2B subunit of the NMDA receptor in
      primary cultures of cerebellar granule neurons over time in culture, with no
      significant change in NR1 expression. This change in NR2 subunit expression was
      associated with the expected changes in functional properties of the NMDA
      receptor (measured as the NMDA-induced increase in intracellular Ca2+), i.e.,
      ifenprodil sensitivity and glycine potency were higher when there was a
      relatively greater proportion of NR2B in the cultured neurons. However, the
      potency of ethanol to inhibit NMDA receptor function was lower when there was a
      greater proportion of NR2B subunits. Previous studies showed that ethanol
      inhibition of NMDA receptor function in cerebellar granule neurons resulted from
      an ethanol-induced decrease in potency of the co-agonist, glycine, and that this
      effect of ethanol was blocked by inhibitors of protein kinase C. Our current
      results suggest that the lower potency of ethanol to inhibit the response of NMDA
      receptors when cerebellar granule neurons are expressing a greater proportion of
      NR2B subunits is a result of the higher affinity of the NMDA receptors for
      endogenous levels of glycine at this point in time.

PMID- 10206187
TI  - A 2-microm DNA-based marker recycling system for multiple gene disruption in the
      yeast Saccharomyces cerevisiae.
AB  - A molecular FRT (Flp recombinase recognition target)-based cassette system for
      multiple gene disruption in the yeast Saccharomyces cerevisiae was developed. FRT
      DNA sequences were designed with different core mutations and subsequently cloned
      in direct orientation upstream and downstream of a marker gene to serve as
      template for the amplification of a set of different gene disruption cassettes.
      After each disruption, the marker can be easily eliminated from its integration
      site by in vivo site-specific recombination between the two identical, mutated
      FRT sequences flanking the marker, leaving behind one FRT sequence with a
      particular point mutation. Since recombination between two FRTs with a different
      core mutation is extremely rare, the possibility of chromosome rearrangements,
      due to site-specific recombination between residual FRTs, is very low. In strains
      containing 2-microm ([cir+]) the site-specific reaction is catalysed by the
      endogenous Flp gene product, whereas in strains without 2-microm ([cir0]), the
      FLP gene is carried on the cassette, together with the marker gene. This system
      can be applied for haploid and diploid [cir+] and [cir0] strains.

PMID- 10206188
TI  - Yeast vitality during cider fermentation: assessment by energy metabolism.
AB  - In an apple juice-based medium, an ethanol-tolerant Australian wine-yeast used
      for cider manufacture produced more than 10% ethanol over a 5 week period. Growth
      of the inoculum (10(6) organisms ml(-1)) occurred to a population of 3.1 x 10(7)
      ml(-1) during the first few days; at the end of the fermentation only 5 x 10(5)
      yeasts ml(-1) could be recovered as colony-forming units on plates. Respiratory
      and fermentative activities were measured by mass spectrometric measurements (O2
      consumption and CO2 and ethanol production) of washed yeast suspensions taken
      from the cider fermentation at intervals. Both endogenous and glucose-supported
      energy-yielding metabolism declined, especially during the first 20 days. Levels
      of adenine nucleotides also showed decreases after day 1, as did adenylate energy
      charge, although in a prolonged (16.5 week) fermentation the lowest value
      calculated was 0.55. AMP was released into the medium. 31P-NMR spectra showed
      that by comparison with aerobically grown yeast, that from the later stages of
      the cider fermentation showed little polyphosphate. However, as previously
      concluded from studies of 'acidification power' and fluorescent oxonol dye
      exclusion (Dinsdale et al., 1995), repitching of yeast indicated little loss of
      viability despite considerable loss of vitality.

PMID- 10206189
TI  - Identification and characterization of individual cyclin-dependent kinase
      complexes from Saccharomyces cerevisiae.
AB  - In S. cerevisiae, regulation of cell cycle progression is known to be carried out
      by a single cyclin-dependent kinase homologue, Cdc28p, acting at different stages
      of the cell cycle in association with various cyclins and other regulatory
      subunits. However, a still unsolved problem is the identification of the
      physiologically relevant substrates of the different Cdc28p kinase complexes
      which participate in this regulation. Purification and characterization of the
      subunit composition and enzymological properties of these Cdc28p complexes would
      therefore contribute substantially to our understanding of the molecular
      mechanisms controlling the cell cycle. We have used a combination of ammonium
      sulphate fractionation, nickel nitrilotriacetate affinity purification, ATP
      Sepharose affinity chromatography and Resource Q ion exchange chromatography to
      purify two different Cdc28p kinase complexes. Using specific clb deletion mutants
      and plasmid or genomic HA epitope-tagged CLBs, we show that one of these
      complexes is composed almost exclusively (93% or greater) of Clb2p-Cdc28p,
      whereas the other is mainly (75% or greater) Clb3p-Cdc28p. These procedures
      provide the basis for the analysis of regulatory, enzymatic and functional
      properties of individual Cdc28p kinase complexes.

PMID- 10206190
TI  - Cloning, targeted disruption and heterologous expression of the Kluyveromyces
      marxianus endopolygalacturonase gene (EPG1).
AB  - The yeast Kluyveromyces marxianus strain BKM Y-719 produces an efficient pectin
      degrading endopolygalacturonase (EPG) that cleaves the internal alpha-1,4-D
      glycosidic linkages to yield oligomers of varying sizes. The EPG1 gene encoding
      this industrially important EPG was cloned by using the polymerase chain reaction
      (PCR) technique and degenerate primers to generate a 135 bp DNA fragment with
      which a genomic library was screened. The cloned fragment contained an open
      reading frame (ORF) of 1083 bp, encoding a 361 amino acid polypeptide. The
      predicted amino acid (aa) sequence of EPG showed similarity with
      polygalacturonases (PGs) of fungi. Analysis of the aa sequence indicated that the
      first 25 aa constitute a signal sequence and a motif (C218XGGHGXSIGSVG230) that
      is usually associated with a PG active site. Pulsed-field gel electrophoresis
      resolved chromosomal bands for K. marxianus BKM Y-719 and using chromoblotting it
      seems that EPG1 is present as only a single copy in the genome.

PMID- 10206191
TI  - Isolation and sequence of the GCR3 homologue from Candida albicans by
      complementation of (delta)gcr3 strain of Saccharomyces cerevisiae.
AB  - To study the function of GCR3, a gene involved in the expression of glycolytic
      genes in Saccharomyces cerevisiae, a Candida albicans gene which complements the
      growth defect of the (delta)gcr3 mutant was isolated. Transformants of this gene
      also recovered the glycolytic enzyme activities. Its DNA sequencing predicted an
      886 amino acid protein with 30.4% identity to the Gcr3p of S. cerevisiae.

PMID- 10206192
TI  - Transcript analysis of 250 novel yeast genes from chromosome XIV.
AB  - The European Functional Analysis Network (EUROFAN) is systematically analysing
      the function of novel Saccharomyces cerevisiae genes revealed by genome
      sequencing. As part of this effort our consortium has performed a detailed
      transcript analysis for 250 novel ORFs on chromosome XIV. All transcripts were
      quantified by Northern analysis under three quasi-steady-state conditions
      (exponential growth on rich fermentative, rich non-fermentative, and minimal
      fermentative media) and eight transient conditions (glucose derepression, glucose
      upshift, stationary phase, nitrogen starvation, osmo-stress, heat-shock, and two
      control conditions). Transcripts were detected for 82% of the 250 ORFs, and only
      one ORF did not yield a transcript of the expected length (YNL285w). Transcripts
      ranged from low (62%), moderate (16%) to high abundance (2%) relative to the ACT1
      mRNA. The levels of 73% of the 206 chromosome XIV transcripts detected fluctuated
      in response to the transient states tested. However, only a small number
      responded strongly to the transients: eight ORFs were induced upon glucose
      upshift; five were repressed by glucose; six were induced in response to nitrogen
      starvation; three were induced in stationary phase; five were induced by osmo
      stress; four were induced by heat-shock. These data provide useful clues about
      the general function of these ORFs and add to our understanding of gene
      regulation on a genome-wide basis.

PMID- 10206193
TI  - Basic phenotypic analysis of six novel yeast genes reveals two essential genes
      and one which affects the growth rate.
AB  - Phenotypic analysis was performed on six mutants of Saccharomyces cerevisiae
      deleted in one of the following open reading frames (ORFs), located on chromosome
      II: YBR254c, YBR255w, YBR257w, YBR258c, YBR259w and YBR266c. Disruption of the
      ORFs was carried out in the diploid strain FY1679 using the kanMX4 marker flanked
      by short sequences homologous to the target locus. Tetrad analysis following
      sporulation of the heterozygous disruptants showed that YBR254c and YBR257w are
      essential genes. YBR257w was later characterized and renamed POP4, its gene
      product being involved in 5.8S rRNA and tRNA processing (Chu et al., 1997). The
      tetrad analysis performed for the heterozygous disruptant for YBR266c showed that
      two of the four viable spores gave colonies of smaller size, reflecting a slower
      growth rate. Growth analysis of the disruptant haploids confirmed this defect at
      30 degrees C and also at 15 degrees C. However, complementation tests failed to
      confirm that the deletion of YBR266c is responsible for this growth defect.
      Growth analysis of the disruptant haploid ybr255w(delta) showed a slower growth
      rate on YPD and minimal medium at 15 degrees C. Finally, no phenotypic effect
      could be detected associated to the disruption of ORFs YBR258c and YBR259w.

PMID- 10206194
TI  - Hyperthyroidism: multiple possibilities in the female patient.
AB  - Hyperthyroidism is a clinical syndrome characterized by an excess of thyroid
      hormone, and its clinical consequences. A suppressed serum TSH concentration is
      the earliest biochemical manifestation of hyperthyroidism. Subclinical
      hyperthyroidism, characterized by suppressed serum TSH concentration alone, has
      important clinical consequences. These include bone loss in postmenopausal women
      and atrial fibrillation. A twenty-four hour radioiodine uptake and radionuclide
      scan are indispensable in the differential diagnosis of hyperthyroidism. Graves'
      Disease, an autoimmune disorder, demonstrates a strong female prevalence; the
      twenty-four hour radioiodine uptake is normal or elevated. Therapeutic options,
      including anti-thyroid drugs, radioactive iodine (131I) and surgery are utilized
      in all age groups. These include use in women during the reproductive years.
      Toxic nodular goiter and "hot" nodules are less common forms of hyperthyroidism;
      these too have normal or elevated radioiodine uptake, with characteristic
      radionuclide scans. Hyperthyroidism with a near-zero radioiodine uptake also has
      important clinical implications. Factitious (exogenous) hyperthyroidism is
      characterized by a low serum thyroglobulin concentration. Treatment consists of
      decreasing the dosage of, or withdrawing, thyroid hormone. Painful subacute
      thyroiditis, a post-vital syndrome, causes spontaneously resolving
      hyperthyroidism, which is often followed by hypothyroidism. The most common cause
      of hyperthyroidism with a low radioiodine uptake is painless, lymphocytic
      subacute thyroiditis. Here too, hyperthyroidism spontaneously resolves and often
      passes through a hypothyroid phase. This phase often requires therapy, and
      permanent mild or severe hypothyroidism may result.

PMID- 10206195
TI  - Managing the climacteric.
AB  - HRT taken for a sufficient duration may reduce the occurrence of osteoporosis and
      of cardiovascular disease by up to 50% and possibly also reduce incidence and
      lessen severity of Alzheimer's disease. Nevertheless, it is often only prescribed
      when women request it to relieve climacteric symptoms. Furthermore, many
      physicians prescribe it for only limited periods of time and few are willing to
      prescribe it to women in their sixties. As with any long-term prevention
      strategy, the uptake of HRT is much lower than the prescription rate, since the
      medication is often abandoned due to side effects or due to lack of motivation.
      But HRT is often abandoned also due to fear of cancer. While physicians may be
      aware of some beneficial effects of HRT, they often have no time to inform their
      patients of them. Alternatively, some of the beneficial effects such as
      cardioprotection or a reduced incidence of Alzheimer's may be less known.
      Likewise, HRT-related side effects or risks such as breast cancer or
      thromboembolic diseases should be discussed prior to HRT prescription. Women need
      to be informed about these potential risks, and this should be done by their
      physician. Surveys have shown that many women feel that they receive insufficient
      information from their physician. The quality of the relationship between
      physician and patient probably has a large influence on HRT acceptance, but very
      few studies have been conducted to assess specifically factors influencing the
      prescription and the continuation rate of HRT. Simple strategies may be among the
      most effective ones; these include listening to patients' fears, complaints and
      questions, and taking the time to answer them. The role of a practice nurse in
      such a setting may be also very important.

PMID- 10206196
TI  - The use of a large-scale surveillance system in Planned Parenthood Federation of
      America clinics to monitor cardiovascular events in users of combination oral
      contraceptives.
AB  - BACKGROUND: The publication of a series of papers based on three large, case
      controlled studies raised questions about the safety of oral contraceptives (OCs)
      containing either desogestrel or gestodene as the progestational agent. In light
      of these studies, the Planned Parenthood Federation of America (PPFA) assessed
      the risk of thromboembolic events in patients who attended its clinics in the
      United States (U.S.). These PPFA patients were prescribed contraceptives
      containing one of the following progestins: desogestrel, levonorgestrel,
      norethindrone, or norgestimate. All of the contraceptives used contained either
      30 or 35 microg of estrogen. METHODS: In this retrospective analysis, the
      association between the occurrence of a thromboembolic event, OC use, and
      progestin type was assessed in a group of PPFA patients. These patients were
      prescribed 2,265,087 woman-years (WY) of OCs from January 1, 1993 to December 31,
      1995. RESULTS: Seventy events (deep vein thromboses [DVTs], pulmonary emboli
      [PEs], myocardial infarctions [MIs], and cerebral-vascular accidents [CVAs] were
      reported; a rate of 3 events per 100,000 WY of use. Five deaths occurred, at a
      rate of 0.22 per 100,000 WY of use. This low rate of incidents appears to be
      related to the younger age of PPFA patients and to the use of uniform guidelines
      for the selection and follow-up patients. Only the lower relative risk of PE
      reached statistical significance, when either norethindrone or norgestimate was
      compared to desogestrel-containing pills, but the absolute risk of these events
      was lower than in other published studies. Though the overall risk varied from a
      low of 1.895 events per 100,000 WY for norgestimate OC users to a high of 3.969
      events per 100,000 WY for desogestrel OC users, these differences were not
      statistically significant. CONCLUSIONS: This study supports the conclusion that
      OCs containing 30 or 35 microg of estrogen, combined with one of the four
      previously identified progestins, carry an extremely low risk of a thromboembolic
      event, particularly when prescribing is based on a defined medical protocol.
      Overall, these four groups of low-dose estrogen-containing OCs appear safer than
      any previously published study has indicated.

PMID- 10206197
TI  - Effect of peritoneal fluid from endometriosis patients on sperm motion
      characteristics and acrosome reaction.
AB  - OBJECTIVE: To determine whether peritoneal fluid from women with endometriosis
      contributes to infertility by impairing sperm motion and functional
      characteristics. METHODS: Women with endometriosis (n = 20) underwent laparoscopy
      for infertility or pelvic pain. Patients undergoing tubal ligation served as
      controls (n = 14). Peritoneal fluid was aspirated from women with endometriosis,
      or from women undergoing laparoscopic tubal ligation. Sperm motility, motion
      characteristics and acrosome reaction were assessed following incubation with
      peritoneal fluid. RESULTS: Sperm motility, motion characteristics, and acrosome
      reaction did not differ significantly between the two groups after 3, 5, or 24
      hours of incubation with peritoneal fluid. CONCLUSIONS: Sperm motion or
      functional characteristics showed no significant impairment when sperm from
      normal donors were incubated with peritoneal fluid from patients with
      endometriosis. It is unlikely that peritoneal fluid in these patients contributes
      to infertility.

PMID- 10206198
TI  - Does ovulation induction affect the pregnancy rate after laparoscopic treatment
      of endometriosis?
AB  - OBJECTIVE: To determine the effectiveness of ovulation induction after
      laparoscopic treatment of endometriosis in an infertile population. DESIGN: An
      observational prospective study in which infertility cases were treated with
      laparoscopic surgery was followed up (mean 11 months), either by treatment
      (ovulation induction) or no further treatment (expectant management) and the
      outcomes recorded. In both groups pregnancies were compared by Cox's regression
      survival model. SETTING: Gazi University Hospital, Department of Obstetric and
      Gynecology, Ankara, Turkey. PATIENTS: Infertile women with different stages of
      endometriosis who were treated by laparoscopic surgery, with a mean duration of
      infertility of 80.7 (+/-50 [SD]) months. INTERVENTIONS: Patients were treated by
      cauterization of the foci, adhesiolysis, endometrioma stripping, and distal tubal
      reconstruction according to their lesions. Postoperatively, patients had either
      ovulation induction (clomiphene, hMG) therapy or no further treatment. MAIN
      OUTCOME MEASURE: Cumulative pregnancy rate of infertile women after laparoscopic
      treatment of endometriosis with or without ovulation induction. RESULTS: A total
      of 36 out of 128 patients became pregnant after laparoscopy, with a 34%
      cumulative pregnancy rate. In the ovulation induction group, relative risk
      (chance) of pregnancy was 1.42 (1.02-2.05, 95 % CI) when the duration of
      infertility was less than 5 years. In this lower risk group, the overall
      cumulative pregnancy rate was 46%--56% and 27% for the ovulation induction and
      expectant management groups, respectively. In the expectant management group, per
      cycle fecundity was 0.021, whereas it was 0.066 and 0.174 (p = 0.001) in the
      clomiphene citrate- and hMG-treated patients, respectively. Expectant management
      significantly increased the likelihood of pregnancy compared to ovulation
      induction in previous pregnancy, stage 1 or 2 endometriosis, and no male
      infertility groups (p = 0.04-0.009). CONCLUSION: After laparoscopic treatment of
      endometriosis, ovulation induction has a positive effect only if done with hMG
      and the duration of infertility was less than 5 years (P<.05).

PMID- 10206201
TI  - Production and functional characterization of recombinant bovine interleukin-8 as
      a specific neutrophil activator and chemoattractant.
AB  - Interleukin-8, a member of the chemokine family of cytokines, is a potent
      neutrophil chemoattractant in many non-rodent species. In this study, recombinant
      bovine interleukin-8 (rbIL-8) was expressed in bacteria as a glutathione-S
      transferase fusion protein. The fusion protein was purified by glutathione
      Sepharose affinity chromatography and recombinant rbIL-8 was eluted by cleaving
      with thrombin. The purified rbIL-8 molecule was approximately 8 kDa and was
      confirmed as authentic IL-8 by Western analysis. Recombinant bovine IL-8 induced
      specific dose-dependent in vitro chemotaxis of neutrophils at doses as low as 1.0
      ng/ml, and this activity was inhibited by pre-treatment of rbIL-8 with a
      monoclonal antibody to ovine IL-8. Neutrophils exposed to rbIL-8 developed
      pseudopodia and became elongated as determined by microscopic analysis and flow
      cytometry. Injection of 3.3 ng to 3.3 microg of rbIL-8 into the skin of a normal
      calf induced dose-dependent recruitment of neutrophils but not eosinophils.
      Intravascular margination of neutrophils was obvious at the injection sites from
      15 to 60 min after administration of rbIL-8, and extravascular neutrophil numbers
      increased steadily from 1 to 18 h after injection. Neutrophils with morphologic
      features of apoptosis were detected in these lesions at 18 and 30 h after
      injection, and this correlated with reduction in the number of dermal
      neutrophils. These results confirm unequivocally that bovine IL-8 functions as a
      neutrophil, but not an eosinophil, chemoattractant in vitro and in vivo.

PMID- 10206199
TI  - Molecular and functional characterization of channel catfish (Ictalurus
      punctatus) neutrophil collagenase.
AB  - Channel catfish (Ictalurus punctatus) neutrophils, like mammalian neutrophils,
      contain a variety of enzymes and lytic peptides that participate in pathogen
      destruction. We have identified and characterized from a channel catfish anterior
      kidney cDNA library a 1.6 kb cDNA that encodes for channel catfish neutrophil
      collagenase. The deduced amino acid sequence has a predicted molecular mass of 53
      kDa. The putative catfish collagenase has nucleotide and amino acid homology of
      51.4% and 45.1%, respectively, with human neutrophil collagenase and 50.4% and
      47.1%, respectively, with mouse neutrophil collagenase. Certain regions of the
      molecule, including the cysteine switch and the putative zinc binding sites, were
      identical to those in the human and mouse genes. Polyclonal antiserum, prepared
      to the fusion protein, recognizes proteins from channel catfish neutrophil
      supernatants with molecular masses of approximately 63, 53 and 28 kDa.
      Supernatants from phorbol dibutyrate stimulated neutrophils were capable of
      degrading type I collagen. In addition, the polyclonal antiserum prevented the
      collagenase activity of the supernatants from stimulated catfish neutrophils;
      whereas, preimmune serum had no effect on collagenase activity of supernatants.
      Supernatants from unstimulated cells or the fusion protein did not possess the
      ability of degrading type I collagen. These results indicate that channel catfish
      neutrophil collagenases share molecular and functional features with mammalian
      neutrophil collagenase.

PMID- 10206200
TI  - Effect of florfenicol on the immune response of rainbow trout (Oncorhynchus
      mykiss).
AB  - Florfenicol, a drug effective against several bacterial diseases of fish, was
      tested for possible immunomodulatory effects. The aim of the study was to follow
      the kinetics of the immune response after vaccination with simultaneous oral
      antibiotic treatment. The fish were immunised with a commercial oil-based
      divalent (furunculosis/vibriosis) vaccine and were simultaneously given oral
      antibiotic treatment. The specific immune response was monitored by analysing the
      levels of specific antibodies with ELISA. As an indicator of the non-specific
      immune response the phagocytic activity of circulating leucocytes was measured by
      a chemiluminescence assay. Total circulating leucocyte counts and differentials
      were also monitored. The disease resistance was evaluated by challenge tests at
      the end of the experiment. The results showed that florfenicol did not have any
      significant effect on antibody production and circulating leucocyte levels but
      caused a suppression in chemiluminescence response/phagocytic cell 5-6 weeks
      after vaccination. The survival after challenge was slightly suppressed by the
      florfenicol treatment. The RPS-value for the vaccinated group was 98% and for the
      florfenicol-treated group was 88%.

PMID- 10206202
TI  - Immunocytochemical demonstration of lymphocyte subsets and MHC class II antigen
      expression in synovial membranes from dogs with rheumatoid arthritis and
      degenerative joint disease.
AB  - The study describes the distribution of canine leucocyte antigens in synovial
      membrane biopsies from six dogs with canine rheumatoid arthritis (CRA) and from
      eight dogs with osteoarthritis (OA) secondary to spontaneous rupture of the
      cranial cruciate ligament (CCL) (n = 5) or patellar luxation (n = 3). Synovial
      membranes from five dogs without evidence of joint lesions were used as control
      tissues. In the subsynovium of dogs with normal joints CD5+, CD4+, CD8+ and alpha
      beta TCR+ lymphocytes were present only in low numbers. With monoclonal antibody
      (mAb) to MHC class II antigen, either none or up to 20-30% of synovial lining
      cells were immunoreactive. Furthermore, scattered MHCII+ stromal cells were seen
      in the deeper subsynovial layer. In synovial membrane biopsies from dogs with CRA
      numerous diffusely and perivascularly distributed CD5+ lymphocytes were found in
      the subsynovium. CD4+ cells outnumbered CD8+ cells and were more numerous in the
      perivascular areas. In all the CRA cases examined, there were markedly higher
      numbers of alpha beta TCR+ cells compared with gamma delta TCR+ cells. With mAb
      to CD21, low numbers of immunoreactive lymphocytes were demonstrated. In all the
      CRA cases, a marked increase of MHC class II antigen expression was noted. In the
      majority of samples, 50% or more than 90% of the synovial lining cells were
      strongly MHC class II+. Throughout the subsynovial layer there were numerous MHC
      class II+ cells and included those with dendritic morphology and inflammatory
      mononuclear cells. Furthermore, marked perivascular immunoreactivity for MHC
      class II antigen was found. In biopsies from dogs with OA, there were markedly
      lower numbers of subsynovial CD5+, CD4+ and CD8+ lymphocytes. T-cells were mainly
      diffusely distributed. In three of the eight OA dogs examined, there was an
      increased percentage of synovial lining cells expressing MHC class II. The
      majority of OA cases had subsynovial major histocompatibility complex (MHC) class
      II+ cells with a dendritic morphology.

PMID- 10206203
TI  - Molecular cloning and physiological effects of brushtail possum interleukin
      1beta.
AB  - Interleukin-1beta (IL-1beta) was isolated from LPS-stimulated brushtail possum
      alveolar macrophages using PCR primers based on conserved regions of mammalian IL
      1beta. The complete cDNA was cloned by 5' and 3' rapid amplification of cDNA ends
      (RACE). The predicted protein of 269 amino acids shared 4346% identity with
      several mammalian IL-1beta proteins. Constructs were made to express the mature
      IL-1beta in Escherichia coli and two recombinant IL-1beta proteins, rpIL-1beta1
      and rpIL-1beta2, which differed in length by four amino acids at the N-terminus,
      were produced. Both proteins induced a weak proliferative response in a possum
      thymocyte assay. Possums injected intravenously with 100 microg of rpIL-1beta1 or
      rpIL-1beta2 showed profound changes in body temperature and numbers of
      circulating leukocytes. A sharp decrease in temperature occurred within 2 h of
      administration followed by an elevation of temperature peaking at 24 h. The
      smaller rpIL-1beta1 protein had a greater effect on temperature than rpIL-1beta2.
      Both rpIL-1beta proteins caused a marked decrease in number of neutrophils and
      lymphocytes at 2-6 h after injection. At 24 h after injection, neutrophil and
      lymphocyte numbers were elevated 6.0-fold and 2.6-fold, respectively in the
      possums injected with rpIL-1beta1 and 3.9-fold and 1.5-fold, respectively in the
      possums injected with rpIL-1beta2. Fibrinogen levels were elevated at 24 and 72 h
      after injection with both proteins. In comparison, neither recombinant bovine IL
      1beta (rbIL-1beta) nor PBS had significant effects on body temperature or blood
      haematology. The studies have shown that the two recombinant forms of IL-1beta
      were biologically active in possums and that the IL-1beta with four fewer amino
      acids at the N-terminus was the more active.

PMID- 10206204
TI  - Effect of antibiotic induced bacterial clearance in the udder on L-selectin
      shedding of blood neutrophils in cows with Escherichia coli mastitis.
AB  - Bacterial clearance, L-selectin adhesion receptor expression and neutrophil
      recruitment during experimentally induced Escherichia coli mastitis were
      investigated. Acute mastitis was induced by injection of 10(4) cfu E. coli into
      both left quarters of 12 clinically healthy lactating cows, 2-6 weeks after
      parturition. Half the cows were treated intravenously 10 h after infection, and
      subcutaneously 30 h after infection with enrofloxacin. In both groups, bacterial
      count, milk serum albumin, milk somatic cell count, circulating leukocyte count
      and L-selectin expression on neutrophils were determined. Both groups responded
      to challenge with udder inflammation and fever. Treatment with enrofloxacin
      affected the elimination rate of bacteria at hours +14, +18, +24, +48, and +72
      after challenge, but not the bacteriological cure rate (five out of six for
      treated and three out of six for nontreated cows). The drop in L-selectin
      expression found following challenge did not differ between groups throughout the
      study. No effect of treatment was found on SCC. Based on these findings, it may
      be concluded that when treatment is administered 10 h after infection, the number
      of bacteria in milk is not correlated with L-selectin expression on circulating
      PMN during experimentally induced E. coli mastitis. The initial bacterial load
      probably dictates the extent of the decrease in L-selectin expression and milk
      somatic cells.

PMID- 10206205
TI  - Molecular cloning and phylogenetic analysis of beluga whale (Delphinapterus
      leucas) and grey seal (Halichoerus grypus) interleukin 2.
AB  - Interleukin 2 (IL-2) is a lymphokine produced by activated T helper lymphocytes
      which exerts immunoregulatory effects on a variety of immune cells, including T
      cells, activated B cells, natural killer cells, and lymphokine-activated killer
      cells. In this study, we cloned and determined the entire beluga whale
      (Delphinapterus leucas) and grey seal (Halichoerus grypus) IL-2-encoding cDNA
      sequences, and analysed their genetic relationships with those from several
      mammalian species obtained from the Genbank Database. The encoding nucleic acid
      sequences of beluga whale and grey seal IL-2 were 465 and 468 bp in length,
      respectively. The identity levels of IL-2 nucleic and deduced amino acid
      sequences from the beluga whale and grey seal with those from the other mammalian
      species, ranged from 59.9% to 89.5%, and 52.9% to 77.3%, and from 61.1% to 93.2%,
      and 58.7% to 88.4%, respectively. Phylogenetic analysis based on both nucleic and
      amino acid sequences showed that the beluga whale IL-2 was closely related to
      that of the ruminant species, which includes the bovine, while the grey seal IL-2
      was closely related to that of the canine.

PMID- 10206206
TI  - Female mating strategy in an enclosed group of Japanese macaques.
AB  - Female Japanese macaques (Macaca fuscata) are noted for mating with multiple
      males and for their ability to exert mate choice. In a captive group of Japanese
      macaques housed at the Primate Research Institute of Kyoto University, Japan,
      behavioral and endocrine data were combined to examine female mating strategies.
      During one breeding season, daily behavioral observations were conducted on
      females who exhibited copulatory behavior. Blood was collected from females twice
      weekly and their ovulatory periods estimated by analyzing hormone profiles.
      Females began mating shortly before ovulation, peaked at ovulation, and continued
      receiving ejaculations for up to ten weeks after conception. Females were more
      responsible than males for inbreeding avoidance with matrilineal kin. Males
      sometimes approached females from their own matriline, but females avoided such
      males and expressed mate choice behavior preferentially toward non-matrilineal
      males. Over the entire mating season, females did not choose non-matrilineal
      males on the basis of displays, dominance rank, age, weight, or weight change
      during the mating season. When females were likely to conceive, however, they
      expressed mate choice behavior toward males who displayed most frequently. Female
      mating strategy may include both mate choice at ovulation and other, non
      procreative functions.

PMID- 10206207
TI  - Cathemerality in the mongoose lemur, Eulemur mongoz.
AB  - Results of a 10 month study of the mongoose lemur (Eulemur mongoz) at Anjamena
      are presented. The activity pattern is documented in detail for both wet and dry
      seasons based on observations conducted over the entire 24 h period. E. mongoz
      was found to be cathemeral throughout the year but exhibited shifts towards more
      diurnal activity in the wet season and more nocturnal activity in the dry season.
      The cathemeral activity pattern in the mongoose lemur appears to be coordinated
      with sunrise, sunset, and day length and modulated by an inhibitory effect of low
      nocturnal light intensity in the forest during the wet season, resulting in
      mainly diurnal activity. Temperature and rainfall may also influence the activity
      pattern. Few advantages to food-related behavior appear to derive from this
      activity pattern, although resource accessibility may be enhanced by nocturnal
      behavior in the dry season, leading to reduction in interspecific competition.
      Cathemerality may also represent a behavioral thermoregulatory mechanism allowing
      the mongoose lemur to conserve energy by being active during the cool nights of
      the dry season. In addition, nocturnal behavior in the dry season probably allows
      avoidance of predation by raptors at the time of year when least protection is
      afforded by vegetation.

PMID- 10206208
TI  - Personality dimensions in adult male rhesus macaques: prediction of behaviors
      across time and situation.
AB  - The idea that consistencies in behavior exist over time and across situations
      underlies human personality research. Although several studies have examined
      personality in nonhuman primates, there are very few data showing the predictive
      power of personality factors. The goal of the present study was to determine
      whether personality dimensions, identified in adult male rhesus monkeys living in
      half-acre cages, predicted behavior in situations different from the one from
      which the dimensions were originally derived and at time points of up to 4.5
      years after the original assessments. Four personality dimensions (Sociability,
      Confidence, Excitability, and Equability) were identified using psychometric
      procedures and were correlated with behaviors recorded in several situations: the
      animals' natal groups, during tests of behavioral responsiveness while in
      individual cages, in small stable and unstable social groups, while viewing
      stimulus videotapes, and during stable social dyads. Results indicated
      substantial predictability. Sociability reflected a greater tendency to engage in
      affiliative interactions. Confidence correlated with more aggressive behaviors
      and with behaviors that suggest less attractiveness. Animals high in Excitability
      were somewhat inconsistent in their social behavior, perhaps reflecting hyper
      responsiveness to novel circumstances and thwarted opportunities for escape.
      Equability appeared to be related to a less aggressive, more passive, style of
      interaction. Excitability and Equability appear to reflect more stylistic
      components of social behavior, whereas Sociability and Confidence may be more
      content-based dimensions. Sociability was strongly related to size of kin network
      in the animals' natal groups, suggesting an important role for ontogeny in this
      dimension. These data suggest that a limited number of personality dimensions
      exist in adult male rhesus macaques, and that these dimensions have predictive
      power that is both long-term and cross situational.

PMID- 10206209
TI  - Female dominance and female social relationships among yellow baboons (Papio
      hamadryas cynocephalus).
AB  - Adult females in a female-bonded, cercopithecine species such as baboons are
      characterized by hierarchically ranked matrilines, i.e., female offspring assume
      rankings just beneath those of their mothers. In this system of closely ranked
      matrilines, a female should engage in significantly more affiliative interactions
      with those individuals who are closely ranked to herself than with those
      individuals who are more distantly ranked. We examine the hypothesis that females
      in this troop of feral yellow baboons (Papio hamadryas cynocephalus) who are
      closely ranked will also show close social affiliation. We collected focal data
      on 23 feral, adult female subjects (253 possible dyads) over approximately 1 year
      at the Tana River National Primate Reserve, Kenya. Following Bramblett's [Behav
      Brain Sci 4: 435, 1981] method of dominance tabulation and utilizing a modified
      version of Smuts' [Sex and friendship in baboons, Hawthorne: Aldine Publishing
      Co., 1985] preferred partner index, we describe and compare the dominance matrix
      and hierarchy, preferred proximity partner and grooming partner sociograms, and
      the social networks of these 23 focal females. Over 1,400 interactions were
      utilized in the dominance tabulations, 41 statistically significant proximity
      partner preferences were documented, and 100 grooming dyads were recorded. We
      examine both partners' ranks and the presence of an infant as possible factors
      influencing proximity and grooming partner preferences. We find that in this
      population there is no direct correspondence between females' ranks and their
      affiliation partners. Neither proximity nor grooming preferences are consistently
      predictable from partners' ranks. While proximity preferences were not
      significantly influenced by the presence of an infant, grooming partner
      preferences were. Females with infants had more grooming partners and were more
      often involved in unidirectional grooming relationships as the recipients than
      were females without infants. We conclude that females' dominance rankings are
      not good predictors of either proximity partner or grooming partner preferences
      and that the presence of an infant does have a significant impact on grooming
      partner preferences in this population.

PMID- 10206210
TI  - Morphometric comparison of Chinese-origin and Indian-derived rhesus monkeys
      (Macaca mulatta).
AB  - Chinese-origin and Indian-derived rhesus monkeys (Macaca mulatta), ranging in age
      from 6 months to 15 years, were weighed and measured during the 1995 inventory of
      the SAIDS breeding colony at the Tulane Regional Primate Research Center. Data
      were analyzed separately for males (n=279) and females (n=554), and an analysis
      of variance was done for five measurements and two indices, with age and country
      of origin as independent variables. All measurements increased significantly with
      age, but Chinese-origin males were heavier, longer, and taller than Indian
      derived males. Chinese-origin juvenile females were heavier and longer than
      Indian-derived juvenile females, but this pattern was reversed for adults.
      Chinese-origin rhesus monkeys exhibited more adult sexual dimorphism than did
      Indian-derived rhesus monkeys. An analysis of Chinese-origin adults that were
      Louisiana-born vs. China-born indicated that Louisiana-born adults were lighter,
      longer, and taller than their China-born parental generation. These differences
      were statistically significant for adult females and descriptively suggestive for
      adult males, and both suggest body and appendage adaptation to a warmer, wetter
      climate.

PMID- 10206211
TI  - Effects of diagnostic levels of color Doppler ultrasound energy on the cell cycle
      of newborn rats.
AB  - Our objective was to evaluate the safety of diagnostic levels of color Doppler
      ultrasound energy in the field of obstetrics and to provide the experimental data
      for its clinical application. After insonating pregnant rats with diagnostic
      levels of color Doppler ultrasound energy, we studied the cell cycles of the
      newborn rats by flow cytometry and factorial analysis. We found that the
      deoxyribonucleic acid content was not affected in any phase of the cell cycle in
      newborn rats by any of the different insonation times and frequencies.

PMID- 10206212
TI  - Differentiation of small hyperechoic renal cell carcinoma from angiomyolipoma:
      computer-aided tissue echo quantification.
AB  - To assess the value of computer-aided tissue echo quantification in
      differentiating small hyperechoic renal cell carcinomas from angiomyolipomas, we
      studied ultrasonographic images of 15 renal cell carcinomas and 20
      angiomyolipomas. After digitizing the images, we measured the absolute gray scale
      values of the renal cortex, central echo complex, and mass. The relative gray
      scale value (%) of the mass was calculated by setting the gray scale value of the
      cortex as 0% and the central echo complex as 100%. The relative gray scale value
      of renal cell carcinomas was in the range of 12 to 73% (mean, 28%), whereas that
      of angiomyolipomas was 30 to 204% (mean, 130%). The differentiation between small
      hyperechoic renal cell carcinomas and angiomyolipomas can be facilitated by
      computer-aided tissue echo quantification.

PMID- 10206213
TI  - Prevalence of aneuploidy with a cardiac intraventricular echogenic focus in an at
      risk patient population.
AB  - The objective of this study was to determine the relative risk for aneuploidy in
      the presence of a cardiac intraventricular echogenic focus in a patient
      population at high risk for aneuploidy. A retrospective cohort study was
      conducted on patients referred to a fetal diagnostic center who were undergoing
      amniocentesis. Records and second trimester sonograms were reviewed.
      Approximately 5100 comprehensive prenatal sonograms were obtained over a 2 year
      study period. Karyotyping by amniocentesis was done in 2412 women; 84 of the
      karyotypes (3.5%) were abnormal. Fetuses with no ultrasonographic findings
      suggestive of aneuploidy had a 1.4% (28 of 1940) prevalence of significant
      chromosomal abnormalities. An intraventricular echogenic focus was found in 149
      of the women with karyotype analysis; 15 had an abnormal karyotype. Fetuses with
      intraventricular echogenic foci had a relative risk of 3.30 of aneuploidy when
      compared to fetuses without echogenic cardiac foci. The presence of an isolated
      intraventricular echogenic focus carried a relative risk of 4.08 compared to
      those fetuses in which ultrasonography had no finding associated with aneuploidy.
      In conclusion, these preliminary data indicate that presence of an
      intraventricular echogenic cardiac focus carries an increased risk of fetal
      aneuploidy.

PMID- 10206214
TI  - Pelvic ultrasonography in Turner syndrome: standards for uterine and ovarian
      volume.
AB  - The purpose of this study was to investigate uterine and ovarian size according
      to age and pubertal stage in patients with Turner syndrome. Ultrasonographic
      evaluation of the uterus and the ovaries was performed in 93 patients with Turner
      syndrome, aged 12 days to 17.85 years. The data were compared with those of 190
      healthy controls. One or both ovaries were detected in 41 of 93 patients (44%).
      Within the prepubertal group, mean uterine volume and mean ovarian volume of the
      patients with Turner syndrome were significantly (P<0.001) lower than those of
      controls (0.5+/-0.2 ml versus 1.0+/-0.3 ml; 0.3+/-0.3 ml versus 0.6+/-0.4 ml,
      respectively). In prepubertal girls, no significant relationship was found
      between age and uterine size or ovarian size. Both uterine volume and ovarian
      volume of 19 women with spontaneous puberty increased during breast development,
      although mean uterine volume and mean ovarian volume were significantly (P<0.01)
      lower than those of pubertal control patients.

PMID- 10206215
TI  - Diagnosis of necrotizing fasciitis in children.
AB  - Necrotizing fasciitis is a rare but progressive soft tissue infection. This
      condition is difficult to recognize in the early phase, when it is often confused
      with cellulitis. We report the cases of four children with necrotizing fasciitis.
      The initial presentation in these cases was cellulitis. Fever and soft tissue
      swelling occurred within 24 h and spreading erythema within 4 to 12 h. Radiologic
      studies of the lesions showed soft tissue thickening. Ultrasonography of the
      lesions demonstrated distorted, thickened fascia with fluid accumulation. Well
      defined, loculated abscesses were demonstrated in two cases. Although typical
      dusky skin and purplish patches were not found in our cases, necrotizing
      fasciitis was strongly suspected on the basis of the clinical course and
      sonographic findings. Ultrasonography also was used as a guide for aspiration of
      pus. Gram-stained smears and bacterial cultures yielded the pathogens. The choice
      of antibiotic therapy was made on the results of smears and culture. All patients
      survived after immediate surgical debridement, intensive antibiotic therapy, and
      aggressive wound care. In conclusion, ultrasonography provides a rapid and
      valuable diagnostic modality for necrotizing fasciitis. The pus obtained through
      sonographically guided aspiration for bacterial culture can allow identification
      of the pathogenic organisms.

PMID- 10206216
TI  - Role of endosonography in the evaluation of gastric malignancies.
AB  - The aims of this study were to stage gastric malignancies and differentiate
      between carcinomas and lymphomas. Twenty-two patients were evaluated with
      endosonography. Tumoral infiltration depth (T stage) and presence of metastatic
      lymph nodes (N stage) were investigated. Five percent of the cases were staged as
      T2, 36% as T3, and 59% as T4. According to the endosonographic examination, 14%
      were NO, 68% were N1, and 18% were N2 malignancies. When compared with results of
      surgery and histopathologic examination, the accuracy was 82% for both T and N
      stages. It can be concluded that endosonography is a valuable imaging modality
      for the local staging of gastric malignancies. Early stage lymphomas can be
      differentiated from carcinomas, but in advanced stages both have similar
      appearance.

PMID- 10206217
TI  - Doppler sonographic evaluation of left atrial function after cardioversion of
      atrial fibrillation.
AB  - Restoration of sinus rhythm is not always followed by immediate return of
      effective atrial contraction. Left atrial mechanical function can be assessed by
      Doppler echocardiography; in the present study we measured the atrial ejection
      force, which is a noninvasive Doppler-derived parameter that measures the
      strength of atrial contraction. The aim of the present study was to evaluate the
      influence of clinical and echocardiographic parameters: duration and cause of
      atrial fibrillation, different modality of cardioversion, and left atrial size
      with respect to the delay in the return of effective atrial contraction after
      cardioversion. Seventy patients were randomly chosen to undergo cardioversion by
      either direct current shock or intravenously administered procainamide
      hydrochloride. The 52 patients who had sinus rhythm restored underwent a complete
      Doppler echocardiographic examination 1 h after the restoration of sinus rhythm
      and after 1 day, 7 days, and 1 month. The relation between clinical variables and
      atrial ejection force was tested. Atrial ejection force was greater immediately
      and 24 h after cardioversion in patients who underwent pharmacologic therapy
      compared to patients treated with direct current shock (11.3+/-3 versus 5+/-2.9
      dynes; P<0.001). In both groups atrial ejection force increased over time. The
      mode of cardioversion was significantly associated with recovery of left atrial
      mechanical function by day 1 in univariate and multivariate analysis (odds ratio,
      0.14; 95% confidence interval, 0.02-1.2). The other variable associated with the
      delay in the recovery of atrial function was a dilated left atrium (odds ratio,
      0.16; 95% confidence interval, 0.12-1.6). Atrial ejection force is a noninvasive
      parameter that can be easily measured after cardioversion and gives accurate
      information about the recovery of left atrial mechanical function. The recovery
      of left atrial function was influenced by the mode of cardioversion and left
      atrial size.

PMID- 10206218
TI  - Evaluation of ocular arterial changes in glaucoma with color Doppler
      ultrasonography.
AB  - The purpose of this study was to evaluate hemodynamic changes of the retrobulbar
      vasculature caused by different intraocular pressures with color Doppler
      ultrasonography. Fifty normal eyes in 25 patients, 13 patients with normal
      tension glaucoma, and 19 patients with acute glaucoma and increased intraocular
      pressure (greater than 30 mm Hg) were enrolled in this study. In 15 of 19
      patients with acute glaucoma patients, follow-up color Doppler ultrasonography
      was also undertaken after laser peripheral iridectomy when the intraocular
      pressure had returned to normal. The peak systolic velocity, end diastolic
      velocity, resistive index, time average maximum velocity, and pulsatility index
      were compared in different vessels, including the central retinal artery, lateral
      posterior ciliary artery, medial posterior ciliary artery, and ophthalmic artery
      in each orbit. The peak systolic velocity, end diastolic velocity, and time
      average maximum velocity of the central retinal artery were significantly lower
      (P<0.01) in acute glaucoma patients than in the control group. The resistive
      index and pulsatility index of the central retinal artery were significantly
      higher (P<0.01) in acute glaucoma patients than in the control group. The end
      diastolic velocity of the lateral and medial posterior ciliary arteries was
      significantly lower in patients with acute glaucoma than in the control group,
      and the resistive index and pulsatility index of both of these arteries were
      significantly higher (P<0.001) in patients with acute glaucoma than in the
      control group. However, no statistical significantly differences were found in
      the peak systolic velocity or time average maximum velocity in either of the
      posterior ciliary arteries; similarly, no statistically significant differences
      were noted in any of the parameters in the ophthalmic artery between the control
      group and the group with acute glaucoma. The pulsatility index of the central
      retinal artery and of the lateral and medial posterior ciliary arteries was
      significantly lower (P<0.01) in acute glaucoma patients after laser therapy than
      in acute glaucoma patients before laser therapy. The resistive index of both
      posterior ciliary arteries was also significantly lower (P<0.004) in acute
      glaucoma patients after laser therapy than before laser therapy. All parameters
      for all vessels examined among the normal subjects, the patients with normal
      tension glaucoma, and the patients with acute glaucoma after laser therapy when
      the intraocular pressure had returned to normal showed no statistically
      significant differences. Color Doppler ultrasonography is a good modality for
      both imaging and studying the hemodynamics of the perioptic nerve vessels.

PMID- 10206219
TI  - Polycystic ovarian syndrome: assessment with color Doppler angiography and three
      dimensional ultrasonography.
AB  - We conducted a three-dimensional ultrasonographic evaluation of the size and
      structure of the ovaries of women who had clinical and biochemical findings
      suggestive of polycystic ovary syndrome. We carried out a comparative color
      Doppler frequency and color Doppler amplitude study of the vascular patterns of
      these ovaries. This study involved 65 women of reproductive age with polycystic
      ovary syndrome and 25 eumenorrheic women who were not taking hormonal
      contraceptives and who had a body mass index below 25 kg/m2. Compared to
      controls, women with polycystic ovary syndrome had larger ovaries and thicker
      stroma, increased impedance in the uterine arteries, increased stromal
      vascularity with decreased impedance that persisted throughout the menstrual
      cycle, and a lack of luteal conversion.

PMID- 10206220
TI  - Percutaneous ethanol is applicable only to small lesions.

PMID- 10206221
TI  - Neovascularization of uterine carcinosarcoma: report of two cases analyzed by
      color Doppler ultrasonography and microvessel density.

PMID- 10206222
TI  - Doppler ultrasonography is a potential tool for the assessment of hip
      vascularity.

PMID- 10206223
TI  - Ultrasonographic findings in niacin-induced hepatitis.

PMID- 10206224
TI  - Doppler sonography is a useful tool to assess the hemodynamic changes caused by
      ANG-II.

PMID- 10206225
TI  - No evidence for linkage between schizophrenia and markers at chromosome 15q13-14.
AB  - Freedman et al. [1997: Proc Natl Acad Sci USA 94:587-592] reported linkage in
      nine multiplex schizophrenia families to markers on chromosome 15, using impaired
      neuronal inhibition to repeated auditory stimuli (P50), a neurophysiological
      deficit associated with schizophrenia, as the phenotype. The highest LOD score
      obtained (5.3 at theta = 0) was for marker D15S1360 mapped to chromosome 15q13
      14, less than 120 kb from the alpha7-nicotinic receptor (CHRNA7) gene. The study
      also reported a small positive LOD score for D15S1360 when examined for linkage
      to the schizophrenia phenotype. Following these findings, we examined three
      polymorphic markers (D15S1360, L76630, and ACTC) on chromosome 15q13-14 near the
      CHRNA7 gene for linkage to schizophrenia, using 54 pedigrees from an independent
      study. Alleles for these three markers were genotyped and analyzed using
      parametric and nonparametric methods. No LOD score above 1.00 was obtained for
      any marker, and affected sib-pair analysis likewise showed no evidence for
      linkage. We conclude that in our families the region around the CHRNA7 locus does
      not contain a major locus for susceptibility to schizophrenia.

PMID- 10206226
TI  - No association between the genes for butyrylcholinesterase K variant and
      apolipoprotein E4 in late-onset Alzheimer's disease.
AB  - Butyrylcholinesterase (BChE) as well as acetylcholinesterase has been suggested
      to be associated with Alzheimer's disease (AD). Lehmann et al. [1997: Hum Mol
      Genet 6:1933-1936] recently reported the synergism between the gene for the K
      variant of BChE (BCHE-K) and the epsilon4 allele of apolipoprotein E (APOE
      epsilon4) in late-onset confirmed AD with Caucasian subjects. The authors found
      that the allelic frequency of BCHE-K was 0.17 in 74 subjects with late-onset
      histopathologically diagnosed AD, which was higher than the frequencies in
      elderly control subjects (0.09) and in other dementias (0.07-0.10). The
      association of BCHE-K with late-onset AD was limited to carriers of APOE
      epsilon4, giving odds ratios of confirmed late-onset AD of 6.9-12.8. In the
      present study, we report the BCHE-K allelic frequencies in late-onset AD cases
      and in age-matched controls of the Korean population, which were 0.22 and 0.17,
      respectively. We could not find any association between BCHE-K and AD regardless
      of APOE epsilon4 carrier status. However, APOE epsilon4 clearly showed higher
      frequency in AD (0.33) than in elderly controls (0.09), giving an odds ratio of
      5.2 (95% confidence interval, 2.7-10.0). Our results do not support the
      conclusion that BCHE-K, or a nearby gene on chromosome 3, acts in synergy with
      APOE epsilon4 as a susceptibility gene for late-onset AD, at least in the Korean
      population.

PMID- 10206228
TI  - Association study of the 5-HT6 receptor gene in schizophrenia.
AB  - Serotonergic (5-hydroxytryptamine; 5-HT) transmission may play an important role
      in the treatment and/or pathogenesis of schizophrenia. Previous studies reported
      that several atypical antipsychotic agents have high affinities for the 5-HT6
      receptor. The 5-HT6 receptor gene polymorphism might contribute to the genetic
      background of this disorder. One hundred and fifty unrelated patients with
      schizophrenia and 150 unrelated healthy controls were genotyped for a biallelic
      polymorphism (267C/T) at the 5-HT6 receptor gene. No significant positive
      association between the 5-HT6 receptor genotype and schizophrenia was observed.
      Our results suggests that the 267C/T polymorphism of the 5-HT6 receptor gene may
      not be involved in the susceptibility to schizophrenia.

PMID- 10206227
TI  - Dopamine D1 receptor gene polymorphism and schizophrenia in Japan.
AB  - We studied the relationship between schizophrenia and the DdeI polymorphism in
      the 5' untranslated region (5'UTR) of the dopamine D1 receptor (DRD1) gene. This
      polymorphism is an A (A1 allele) to G (A2 allele) transition in the 5' UTR of
      exon 2 at bp -48 (A-48G). One hundred forty-eight schizophrenics and 148 control
      subjects were investigated. No significant differences in genotypic counts and
      allele frequencies between schizophrenics and controls were found. Although a
      significant difference between the patients classified as disorganized type and
      the controls was discovered both in genotypic counts and allele frequencies,
      neither association proved significant when a Bonferroni correction was used.
      Moreover, there were no differences in scores of main symptoms of schizophrenia
      based on the Manchester Scale between patients with A1/A1 genotype and those with
      A1/A2 genotype. These findings suggest that this gene may not be involved in the
      pathogenesis of schizophrenia.

PMID- 10206230
TI  - Association analysis between a Cys23Ser substitution polymorphism of the human 5
      HT2c receptor gene and neuronal hyperexcitability.
AB  - Transgenic mice lacking a functional 5-HT2c receptor gene are extremely
      susceptible to audiogenic seizures, suggesting that 5-HT2c receptors mediate
      inhibition of neuronal network excitability. The present association study tested
      the hypothesis that a Cys23Ser substitution polymorphism within the human 5-HT2c
      receptor gene modulates neuronal excitability. Genotypes of the Cys23Ser
      polymorphism were assessed in 454 subjects of German descent, comprising: 1) 93
      severely affected alcohol-dependent males with a history of alcohol withdrawal
      seizure or delirium, 2) 119 patients affected by an idiopathic generalized
      epilepsy, and 3) 242 controls. Both sexes were analyzed separately because of the
      X-chromosomal location of the 5-HT2c receptor gene. The allele frequencies of the
      Cys23Ser variants did not differ significantly between the controls and either
      the severely affected alcohol-dependent males (P = 0.34), or patients with
      idiopathic generalized epilepsy (P > 0.57). Our results suggest that the common
      Cys23Ser substitution polymorphism of the human 5-HT2c receptor gene does not
      confer susceptibility to neuronal hyperexcitability in either idiopathic
      generalized epilepsy or alcohol withdrawal seizure or delirium.

PMID- 10206229
TI  - Serotonin transporter gene (5-HTT) polymorphisms and compulsive buying.
AB  - We examined a panel of 21 patients diagnosed with compulsive buying for two DNA
      sequence polymorphisms found in the gene that encodes the serotonin transport (5
      HTT). One polymorphism, found in the promoter region of the 5-HTT gene, involves
      a 44-base pair (bp) deletion, and the other, found in the second intron, is due
      to variable numbers of a repeat sequence. We also typed a panel of 38
      psychiatrically normal controls for both 5-HH markers. When compared to this
      control panel, no significant differences were seen for either 5-HTT marker among
      the compulsive buyers.

PMID- 10206231
TI  - Parent-of-origin effect in panic disorder.
AB  - Parent-of-origin effect was examined in a series of 64 pedigrees with panic
      disorder (PD) under both the narrow and broad diagnostic models. The narrow
      diagnostic model defined the affected phenotype to include only the "definite"
      and "probable" forms of PD, whereas the broad diagnostic model included the
      entire PD symptomatology. The pattern of maternal vs. paternal transmission of
      disease was analyzed through a number of comparisons. These comparisons were
      performed first on all pedigrees and then on a subset of "pure" pedigrees
      including only strictly maternal transmission or strictly paternal transmission
      of PD. There were no significant differences in the proportion of offspring born
      to transmitting mothers vs. transmitting fathers under either diagnostic model or
      pedigree set. When the difference in the sex ratio among affected offspring from
      both transmission types was considered, only the "pure" pedigree sample under the
      broad diagnostic model yielded nominally (i.e., not corrected for multiple tests)
      significant results (P < .05). Also, the comparisons of cumulative lifetime risk
      for PD between offspring of transmitting mothers and fathers gave some nominally
      significant results; when affected and unaffected offspring were considered,
      significant results were observed under the narrow and broad diagnostic models, P
      < .0005 and P < .05, respectively. These findings must be considered provisional
      until confirmed by further study.

PMID- 10206232
TI  - Lipoprotein lipase mutations and Alzheimer's disease.
AB  - Lipoprotein lipase (LPL) helps transfer lipids from lipoprotein particles to
      cells. In the brain, LPL is present in Alzheimer's disease (AD) amyloid plaques.
      LPL binds apolipoprotein E (ApoE) lipoprotein particles and low-density
      lipoprotein receptor-related protein (LRP), an ApoE receptor. Since polymorphisms
      in both ApoE and LRP influence AD risk, we sought to determine whether LPL
      mutations also affect AD risk. In a case-control study, the frequencies of two of
      the most common known LPL mutations were measured in European-Americans either
      clinically diagnosed or pathologically confirmed as AD or normal control (N)
      subjects. In clinically diagnosed subjects, the Ser447Ter mutation comprised 9.8%
      (62/630) of alleles in N and 3.8% (9/238) in AD, a significant difference (P =
      0.0057), while the Asn291Ser mutation comprised 1.1% (5/460) of alleles in N and
      5.1% (8/158) in AD, also a significant difference (P = 0.0073), though in
      pathologically confirmed subjects the allele frequencies for AD did not
      significantly differ from N for either mutation. In clinically diagnosed
      subjects, LPL mutations were associated with altered AD risk, suggesting a
      potential role for LPL in the causation of AD. Further studies in different
      populations should help clarify the questions raised by these results.

PMID- 10206233
TI  - Risk of Alzheimer's disease is associated with a very low-density lipoprotein
      receptor genotype in Northern Ireland.
AB  - The epsilon-4 allele of apolipoprotein E (APOE) is associated with increased risk
      of Alzheimer's disease (AD), but the pathogenic mechanism is unknown. The 5
      repeat allele of a CGG repeat polymorphism in the 5' untranslated region of the
      very low-density lipoprotein receptor (VLDL-R) gene, a receptor for apoE, has
      been found to be associated with increased risk of AD in a Japanese population.
      Other groups have been unable to replicate this in American Caucasian
      populations. A case-control study utilizing a clinically well-defined group of
      late-onset AD patients (n = 108) and age- and sex-matched control subjects (n =
      108) from Northern Ireland was performed to test this association in a relatively
      homogeneous population. The 9,9 genotype of the VLDL-R was found to be
      significantly increased in patients compared to controls (P = 0.003; Pcorr =
      0.035), leading to an increased risk of AD to subjects with this genotype (OR =
      3.9; 95% CI, 1.52-11.25). In contrast to results from the Japanese study, the 5
      repeat allele was found to be significantly reduced in the patient group when
      compared to controls (P = 0.008; Pcorr = 0.047). The results from this study
      suggest that individuals who have the 9,9 genotype of the VLDL-R gene are at
      increased risk of AD in Northern Ireland.

PMID- 10206234
TI  - Neuroanatomic and neuropsychological outcome in school-age children with
      achondroplasia.
AB  - We previously reported on cognitive and respiratory factors in a series of
      infants with achondroplasia (ACH). We now present the results of
      neuropsychological evaluation and magnetic resonance imaging in 16 school-age
      children with ACH, 7 of whom had been included as infants in our previous report.
      We examined the neuroanatomic and cognitive status of this sample, as well as the
      predictive stability of the prior infant assessment. Seventeen normally
      developing children of average stature and 21 preterm children with arrested
      (compensated, unshunted) hydrocephalus constituted the comparison groups. Brain
      volumes of children with ACH were significantly larger than those of the
      comparison groups. In addition, children with ACH exhibited kinking of the
      medulla and neuroanatomic abnormalities consistent with arrested hydrocephalus,
      including enlarged ventricles and hypoplasia of the corpus callosum. Cognitive
      abilities at school age were average, although mild deficits were seen on visual
      spatial tasks, similar to those obtained by the hydrocephalic comparison group.
      Only gross motor coordination deficits distinguished the ACH group from the
      hydrocephalic controls. Infant assessment overestimated later school-age IQ
      scores in those infants with ACH who scored above average. These findings point
      to generally preserved cognitive skills in selected children with ACH at early
      school age, although children with ACH should be evaluated individually as they
      are at risk for cognitive, academic, and motor deficits.

PMID- 10206235
TI  - Lack of association between the hSKCa3 channel gene CAG polymorphism and
      schizophrenia.
AB  - Genetic anticipation, a phenomenon characterized by increased severity of
      symptoms and earlier age at onset of a disease in successive generations, is
      believed to be present in schizophrenia. In several neurodegenerative diseases
      showing anticipation, the mutation causing the disease is an expanded
      trinucleotide repeat. Therefore, genes containing trinucleotide repeats prone to
      expansion have become a suitable family of candidate genes in schizophrenia. A
      human calcium-activated potassium channel gene (hSKCa3), possibly mapping to
      chromosome 22q11-13, a region previously linked to schizophrenia, was recently
      described. This gene contains two contiguous expressed CAG repeat stretches.
      Recently, long allelic variants of one of these CAG repeats were found to be
      overrepresented in schizophrenic patients compared to normal controls. In this
      study we attempted to replicate this result and to study the relationship between
      the length of this CAG repeat on the one hand and the severity and age at onset
      of the disease on the other hand. No association with the disease or correlation
      with the severity of schizophrenia was identified. In addition, hSKCa3 was mapped
      to chromosome 1. Our results do not support the involvement of this particular
      CAG repeat-containing gene in schizophrenia.

PMID- 10206236
TI  - Tourette syndrome and the norepinephrine transporter gene: results of a
      systematic mutation screening.
AB  - Tourette syndrome (TS) is a complex inherited neuropsychiatric disorder
      characterized by multiple motor and phonic tics. Involvement of central
      norepinephrine mechanisms is suggested by central norepinephrinic hyperactivity
      in patients with TS and by the therapeutic effects of the presynaptic alpha2
      adrenergic agonist clonidine. The norepinephrine transporter gene (NET) was
      systematically screened by single-strand conformation analysis for genetic
      variants, including the whole coding region and adjacent exon-intron boundaries
      in 43 patients with TS and 46 healthy controls. We detected 12 DNA sequence
      variants, among them four missense mutations (Val69Ile, Thr99Ile, Va1245Ile, and
      Gly478Ser). The observed missense mutations may alter conformational
      rearrangements during gating of the transporter, assembly of subunits, and
      norepinephrine-specific uptake affinity. Allele frequency and genotype
      distribution of the genetic variants showed no differences between TS patients
      and controls. No mutation of likely functional significance was found that
      distinguished TS patients from healthy controls, indicating that genetic variants
      of the NET gene are not causally related to Tourette syndrome.

PMID- 10206237
TI  - 14-3-3 protein eta chain gene (YWHAH) polymorphism and its genetic association
      with schizophrenia.
AB  - Recent genetic analyses have suggested a linkage between schizophrenia and the
      chromosomal region 22q12-q13. 14-3-3 protein, abundant in the brain, mediates
      interactions between diverse molecules of biological activities; its gene was
      recently mapped to chromosome 22q12.1-q13.1. We therefore investigated allele
      frequencies of a variable number of tandem repeat (VNTR) in the 5'-noncoding
      region of the 14-3-3 eta chain gene in controls and schizophrenics. The
      frequencies of the two-repeat allele were significantly higher (P < 0.05) in the
      schizophrenics, and particularly in those with onset before age 22 (early-onset
      schizophrenics, P < 0.02), than in the controls. The odds ratio was significantly
      increased in the early-onset schizophrenics homozygous for the two-repeat allele
      (OR = 3.3, 95% CI = 1.1-9.7). The 14-3-3 eta chain gene is a potential
      susceptibility gene for schizophrenia, and particularly for early-onset
      schizophrenia.

PMID- 10206238
TI  - Allelic variants of dopamine receptor D4 (DRD4) and serotonin receptor 5HT2c
      (HTR2c) and temperament factors: replication tests.
AB  - The contribution of genetic factors to personality differences between
      individuals is evidenced by twin and adoption studies. Ebstein et al. [1996,
      1997a, 1997b] reported an association between the long repeat allele of the
      dopamine D4-exon-III receptor polymorphism and the human personality dimension
      novelty seeking (NS), between the 5HT2c-ser-23 allele and reward dependence, and
      an interaction between both receptor polymorphisms and reward dependence.
      Subsequent replication tests mainly reported controversial results for the
      association between DRD4-exon-III long repeat and NS. We examined a homogeneous
      study population of 190 healthy male students of middle European descent, aged
      between 20 and 30 years using Cloninger's TPQ in order to replicate Ebstein's
      findings. Using a significance level of 1%, no association between the long
      repeat of the DRD4-exon-III polymorphism and NS and between the 5HT2c receptor
      polymorphism and reward dependence was found, but a significant interaction
      effect of DRD4 and 5HT2c receptor polymorphisms on reward dependence was observed
      in accordance to Ebstein's report.

PMID- 10206239
TI  - Genetic linkage study of panic: clinical methodology and description of
      pedigrees.
AB  - This paper describes the clinical methodology and currently collected pedigrees
      from an ongoing genetic study of panic disorder. The main objectives are to (1)
      document the clinical aspects of the study for current [Knowles et al., 1998: Am.
      J. Med. Genet. (Neuropsychiatr. Genet.) 81:138-147] and future reports of genetic
      analysis; (2) assist other investigators working on the genetic aspects of panic
      disorder who wish to compare results; and (3) illustrate the numerous judgment
      calls required in such studies that may lead to methodological variability and
      could account for differences in findings between studies. We also describe
      initial strategies to identify more genetically homogeneous panic disorder
      subtypes. Families were recruited through letters to magazines, word of mouth
      referral, and screening in anxiety disorder clinics and were asked to participate
      if at initial diagnostic screening they appeared to have at least three members
      (in two generations) affected with panic disorder. Diagnostic evaluations
      included a lifetime clinician-administered semistructured psychiatric interview,
      family history assessment, and pertinent medical records. Diagnoses for linkage
      analysis are derived from a best-estimate procedure that includes independent
      review of all materials by two senior investigators. All clinical evaluations
      were done blind to genotypes. Fifty-five pedigrees including 679 individuals have
      been collected to date. DNA is available from 500 family members of whom almost
      half (48%) are definitely or probably affected with panic disorder. Most (93%) of
      these subjects were directly interviewed, and the clinical data include not only
      lifetime psychiatric and medical diagnoses and but also detailed narrative
      histories describing sequence and context of symptoms. Family sizes range from 4
      36 individuals (mean = 12.3) and the number of affected individuals per family
      from 2-12.

PMID- 10206240
TI  - Evaluation of a putative major susceptibility locus for juvenile myoclonic
      epilepsy on chromosome 15q14.
AB  - Juvenile myoclonic epilepsy (JME) is a genetically determined common subtype of
      idiopathic generalized epilepsy (IGE). Significant evidence for linkage has been
      reported for a susceptibility locus for JME in the chromosomal region 15q14 that
      harbors the gene encoding the alpha7 subunit of the neuronal nicotinic
      acetylcholine receptor (CHRNA7). The present study was designed to test the
      earlier linkage finding and to explore whether this susceptibility locus is
      involved in the epileptogenesis of a broader spectrum of IGE syndromes.
      Multipoint parametric and nonparametric linkage analyses with seven
      microsatellite polymorphisms encompassing the region of the CHRNA7 gene were
      performed using two diagnostic schemes of JME-related traits in two groups of
      multiplex families ascertained through probands with either JME (n = 27) or
      idiopathic absence epilepsy (n = 30). The present linkage study failed to
      replicate evidence for a major susceptibility locus for JME in the region
      encompassing the CHRNA7 gene. In addition, we found no hint in favor of linkage
      to 15q14 under the broad diagnostic scheme in any of the sets of families. If
      genetic variation in this region confers susceptibility to JME, then its effect
      size might be too small or its occurrence too rare to be detected in the
      investigated families.

PMID- 10206241
TI  - Evidence for bilineal inheritance of physiological indicators of risk in
      childhood-onset schizophrenia.
AB  - Childhood-onset schizophrenia is proposed to be associated with increased genetic
      loading compared with adult-onset schizophrenia because of its earlier age of
      onset and generally greater severity of symptoms. Diminished suppression of P50
      auditory evoked responses to repeated stimuli and elevated anticipatory saccades
      during smooth pursuit eye movements are markers of genetic risk that are found in
      members of families with schizophrenia even in the absence of the full clinical
      disorder and appear to be transmitted in a single gene autosomal dominant
      fashion. Adult-onset schizophrenia is generally associated with one parent who
      demonstrates abnormal P50 sensory gating and elevated anticipatory saccades and
      one parent who is normal on the physiologic measures (i.e., unilineal
      inheritance). This study investigates whether childhood-onset schizophrenia is
      similarly unilineal or is associated with the inheritance of genetic risk factors
      from both parents (i.e., bilineal inheritance). Ten childhood-onset schizophrenic
      probands and their parents were studied. Their P50 sensory gating and
      anticipatory saccades were compared with adult-onset schizophrenic probands and
      their parents. Bilineality, measured as physiological impairment in both parents,
      occurred more frequently in childhood-onset probands than in adult-onset probands
      for both P50 sensory gating deficits (60% versus 13%) and elevated anticipatory
      saccades (60 versus 0%). Additionally, childhood-onset schizophrenic probands
      performed more poorly than adult-onset probands on the anticipatory saccade
      measure. This physiological evidence suggests that childhood-onset schizophrenia
      may be associated with increased genetic loading because of contributions of
      genetic risk from both parents.

PMID- 10206242
TI  - Psychosocial competence of unselected young adults with sex chromosome
      abnormalities.
AB  - Very little is known about the adult adaptation of individuals with sex
      chromosome abnormalities (SCA) except for a few reports based upon biased samples
      of clinically identified patients. This first report from the Denver SCA study on
      the adult psychosocial adaptation of 36 unselected propositi, identified at
      birth, shows a continuation of mild psychological and social problems.
      Psychiatric interviews and self-reported information revealed that adaptation is
      quite variable, with many of the nonmosaic propositi not faring as well as their
      siblings, but in a few instances exceeding the success of brothers and sisters.
      Within this group of SCA subjects a subset demonstrated more marked pathology and
      a tendency to over-rate their social adaptation relative to the psychiatric
      interviewer, suggesting that the exclusive use of self-report questionnaires may
      not provide accurate assessment of psychological characteristics in this and
      other special populations. The full adult SCA behavioral phenotype has not yet
      been established but is emerging through additional reports from this and other
      studies of unselected SCA adults.

PMID- 10206243
TI  - Application of life table analysis to the onset of dementia in a genetically
      informative design.
AB  - The primary objective of this study was to estimate the survival function for
      time to onset of dementia in initially unaffected twins from when their partner
      (index proband) was diagnosed with dementia of the Alzheimer's type. Survival
      functions generated by life table analyses were compared by zygosity and gender.
      Sixty-one twin pairs where at least one member had been diagnosed with dementia
      of Alzheimer's type were included in the analyses. Additionally, both members of
      the twin pair had to be alive at the time the index proband was diagnosed with
      dementia. The probability of remaining cognitively intact within the first three
      years after the proband was diagnosed was high (0.93, 95% CI 0.89, 1.0), but
      after 15 years the probability of remaining intact was low (0.34, 95% CI 0.16,
      0.52). Age of onset of the index proband was a significant covariate in the
      survival functions. There were significant differences in the survival functions
      for monozygotic (MZ) and dizygotic (DZ) co-twins (chi2 = 3.86, 1, P < 0.05),
      evidencing a genetic component for age of onset for dementia, but there were no
      significant differences between men and women.

PMID- 10206244
TI  - Apolipoprotein E alleles in childhood-onset schizophrenia.

PMID- 10206245
TI  - Internal fixation of femoral neck fractures with posterior comminution: a
      biomechanical study.
AB  - OBJECTIVES: This study was performed to determine whether four cancellous lag
      screws provide significantly improved rigidity and fixation strength compared
      with three screws for fixation of displaced femoral neck fractures with posterior
      comminution. DESIGN: Biomechanical cadaver study. INTERVENTION: Eight pairs of
      mildly osteopenic femurs were selected, and each pair was fixed with three or
      four cancellous lag screws (randomly assigned) after the creation of a simulated
      femoral neck fracture with posterior comminution. A separate comparison with an
      unmatched group of six similar femurs with a simulated femoral neck fracture
      without posterior comminution and instrumented with three screws was performed to
      investigate the effect of posterior comminution. MAIN OUTCOME MEASUREMENT: The
      specimens were non-destructively tested to determine fixation rigidity in axial
      and anterior loading. Cyclic axial loading was then performed for 10,000 cycles;
      the femurs were retested for rigidity and finally were axially loaded until
      failure. RESULTS: The femurs with a posterior defect stabilized with three screws
      had significantly less resistance to axial and anterior displacement and
      sustained significantly lower axial loads to failure than those stabilized with
      four screws. The specimens instrumented with three screws without a posterior
      defect exhibited greater resistance to displacement in anterior loading and
      sustained greater axial loads to failure than those with a posterior defect
      stabilized with three screws. CONCLUSION: This study suggests that there are
      benefits to using four screws for fixation of femoral neck fractures with
      posterior comminution.

PMID- 10206246
TI  - A comparison of mechanical strength of the femoral neck following locked
      intramedullary nailing using oblique versus transverse proximal screws.
AB  - OBJECTIVE: The objective of the present study was to determine whether the 130
      degree oblique or transverse proximal locking technique significantly enhances or
      diminishes the strength of the intramedullary nail-to-bone construct in a
      "stancelike" loading configuration. DESIGN: Six paired fresh frozen femora were
      randomized to locked intramedullary nailing with either the 130-degree proximal
      locking technique or the transverse locking technique and tested in axial
      compressive loading. Torsion, shear, and impact loading were not tested.
      PATIENTS/PARTICIPANTS: Six paired adult fresh frozen cadavers. INTERVENTION: An
      unreamed eleven-millimeter by thirty-eight-centimeter intramedullary nail was
      placed under direct visualization in each femur. Proximal locking was randomly
      performed on each pair with either two transverse screws or a single oblique
      screw. Each femur was loaded to failure at a rate of 50.8 millimeters per minute
      (two inches per minute) by using an Instron tensiometer. Radiographs after nail
      insertion and after failure were obtained. MAIN OUTCOME MEASURES: Load to
      fracture and fracture pattern. RESULTS: A significant difference between load to
      fracture was observed across femora of different donors (p < 0.001). No
      significant difference was observed in paired femora from the same donor when
      using either 130-degree or transverse proximal locking (p > 0.05). This result
      was based on nonanatomical axial loading that approximated loading during stance,
      without hip abductor loads to help stabilize the femur. CONCLUSION: Neither
      technique preferentially predisposed the construct to failure for the loading
      pattern tested. The mode of failure was the same in all cases, with failure
      beginning at the nail insertion site.

PMID- 10206247
TI  - The effects of nutritional status on outcome after hip fracture.
AB  - OBJECTIVE: To determine the effect of nutrition on patient outcome after hip
      fracture. STUDY DESIGN: Retrospective review of prospectively collected data.
      METHODS: Four hundred ninety hip fracture patients had albumin and total
      lymphocyte count levels determined at the time of admission and constituted the
      study population. These variables were examined as predictors for outcomes,
      including: in-hospital mortality, postoperative complications, hospital length of
      stay, hospital discharge status, one-year mortality rate, ambulatory ability, and
      independence in basic and instrumental activities of daily living twelve months
      after surgery. RESULTS: Eighty-seven patients (18 percent) were found to be
      malnourished on hospital admission based on a preoperative albumin level of < 3.5
      grams/deciliter, and 280 patients (57 percent) based on a total lymphocyte count
      of < 1,500 cells/milliliter. An albumin level of < 3.5 grams/deciliter was
      predictive for increased length of stay (p = 0.03) and for in-hospital mortality
      (p = 0.03). A total lymphocyte count < 1,500 cells/milliliter was predictive for
      one-year mortality (p < 0.01). Patients with abnormal albumin and total
      lymphocyte count were 2.9 times more likely to have a length of stay greater than
      two weeks (p = 0.03), 3.9 times more likely to die within one year after surgery
      (p = 0.02), and 4.6 times less likely to recover their prefracture level of
      independence in basic activities of daily living (p < 0.01). Neither parameter
      was predictive for patients developing a postoperative complication, hospital
      discharge status (home versus nursing home), recovery of prefracture ambulatory
      ability, or independence in instrumental activities of daily living at twelve
      month follow-up. CONCLUSION: Patients at risk for poor outcomes after hip
      fracture can be identified using relatively inexpensive laboratory tests such as
      albumin and total lymphocyte count.

PMID- 10206248
TI  - Segment transport employing intramedullary devices in tibial bone defects
      following trauma and infection.
AB  - OBJECTIVES: To compare two different methods of segment transport in
      posttraumatic and postseptic tibial defects by employing intramedullary tibial
      nails as the fixation system and to evaluate differences in the complication rate
      between external fixation and wire towropes as the transport system. DESIGN:
      Randomized, prospective, nonblinded study. SETTING: Level 1 trauma center.
      PATIENTS: Thirty patients with posttraumatic or postseptic defects of the tibial
      shaft were admitted at our center between January 1994 and December 1995. For
      study purposes, they were divided into two groups with fifteen patients in each.
      METHODS: All thirty patients underwent a standardized therapy protocol consisting
      of three phases: (a) eradication of infection, (b) restoration of soft tissue
      defects, and (c) bone segment transport. The first two phases were identical for
      both groups. The third phase was different: in Group A transport of the segment
      was performed with a combination of intramedullary nail and wire towrope; in
      Group B the intramedullary nail was combined with an external fixation device. We
      then evaluated both subjective data (patient comfort, restrictions in
      physiotherapy) and objective data (mobility of knee and ankle joint, transport
      time, reoperations, complications) to determine treatment success. RESULTS: Both
      methods are useful for segment transport in patients with tibial shaft defects
      following trauma and infection. The relative transport time was shorter in Group
      A than in Group B (12.2 versus 13.7 days/centimeter; p = 0.002). Group B also
      recorded a significantly higher complication rate than did Group A (septic
      complications, twenty-six versus six events; necessary recorticotomies, four
      versus zero events). CONCLUSIONS: An intramedullary nail and wire towrope proves
      to be a reliable combination for segment transport in tibial defects following
      trauma and infection and provides a relatively high patient comfort rate and a
      low complication rate.

PMID- 10206249
TI  - Influence of plate design on cortical bone perfusion and fracture healing in
      canine segmental tibial fractures.
AB  - OBJECTIVE: To investigate whether or not the limited contact design of the low
      contact dynamic compression plate (LCDCP) provides advantages over the dynamic
      compression plate (DCP) in the context of cortical bone blood flow, biomechanical
      properties, and remodeling of bone in segmental tibial fractures. DESIGN:
      Randomized trial using canines. SETTING: Animal research laboratory.
      PARTICIPANTS: Eleven canines. INTERVENTION: Segmental tibial fractures were
      surgically created in canine tibiae. The tibiae were reduced and stabilized with
      316L stainless-steel, 3.5-millimeter, ten-hole plates: LCDCP (n = 5) or DCP (n =
      6). MAIN OUTCOME MEASUREMENTS: Laser Doppler flowmetry evaluated cortical bone
      perfusion in the proximal tibia, segmental piece, and distal tibia (a) before
      fracture, (b) after fracture, (c) immediately after plating, and (d) at ten
      weeks. After the dogs were killed at ten weeks, bending stiffness and load to
      failure of the tibiae were assessed. Tibial cortical bone porosity and new bone
      formation were measured. RESULTS: Cortical bone blood flow was similar between
      the LCDCP and DCP groups throughout the study. Bending stiffness and load to
      failure of the tibiae were similar between the two groups. Whereas cortical bone
      porosity and new bone formation were higher in all plated tibiae at ten weeks
      compared with controls, no differences in cortical bone porosity were seen
      between the LCDCP and DCP groups. There was a trend toward significantly more new
      bone formation in the LCDCP group. CONCLUSION: The LCDCP is not advantageous in
      fracture healing or restoration of cortical bone perfusion to devascularized
      cortex in segmental fractures when plate fixation has been chosen for fracture
      stabilization. The overall injury following segmental devascularization seems
      more important to outcome than the type of implant used for fracture fixation up
      to ten weeks.

PMID- 10206250
TI  - Regeneration of segmental diaphyseal defects in sheep tibiae using resorbable
      polymeric membranes: a preliminary study.
AB  - OBJECTIVE: To investigate whether a long bone cortex of well-defined thickness
      can be regenerated by using an anatomically designed membranous resorbable "tube
      in-tube" implant and to establish the functions of membranes in the healing of
      segmental diaphyseal bone defects larger than the "critical size." DESIGN: Bone
      healing in segmental diaphyseal defects larger than the critical size in the
      sheep tibiae covered with a single porous tubular membrane or implanted with
      anatomically shaped porous double tube-in-tube membranes was evaluated. Membranes
      with different pore structures were applied alone and/or in combination with
      autogenous bone graft. BACKGROUND: Healing of segmental diaphyseal bone defects
      in animals can be enhanced by covering the defects with resorbable polylactide
      membranes. Based on the results of bone healing in defects ten millimeters long
      in the rabbit radii, it was suggested that the membrane prevents muscle and soft
      tissue from invading the defect and maintains osteogenic cells and osteogenic
      substances within the space covered with membrane, thus promoting new bone
      formation. The functions of membranes may differ, however, depending on the size
      and the location of the defect and on the experimental species used. Bone defects
      larger than the critical size may not heal at all, even if membranes are used.
      The critical-size defect is defined as the smallest bone defect that does not
      heal spontaneously when covered with polymeric membranes. To heal such defects,
      it is mandatory that membranes are used in combination with autogenic bone graft
      and/or a suitable bone substitute. If bone graft is used to fill the defect, the
      structure and geometry of the covering membrane will determine whether the graft
      will be vascularized and/or nourished from the surrounding soft tissue and, in
      consequence, survive. It can be appreciated that bone healing in areas of good
      vascularity should be more efficient than bone healing in poorly vascularized
      areas. The influence of all these factors on healing of bone in segmental
      diaphyseal defects covered with membranes is not known. METHODS: Four-centimeter
      long diaphyseal segmental defects in the tibiae of six- to seven-year-old Swiss
      mountain sheep were covered with resorbable membranes from poly(LDL-lactide). In
      Group 1, a single microporous external membrane was used. In Group 2, one
      microporous membrane was inserted into the medullary cavity at the cut ends of
      the tibiae (internal membrane), and the other microporous membrane was placed on
      the outer surface of the cortex (external membrane). In Group 3, a single
      microporous external membrane was also laser-perforated to produce openings with
      a diameter in the range of 800 to 900 micrometers. In Group 4, the defect was
      filled with autogenous cancellous bone graft and covered with a single perforated
      membrane. In Group 5, one perforated internal membrane was inserted into the
      medullary cavity at the cut ends of the tibiae, and the other perforated membrane
      was placed on the outer surface of the cortex. Group 6 was identical to Group 5,
      except that cancellous bone graft was placed in the space between these two
      membranes. RESULTS: There was no bone healing in Groups 1, 2, 3, and 5. Only in
      Groups 4 and 6 did the defects heal. In Group 4, new bone was dispersed across
      the "medullary canal" formed by the membrane. In Group 6, the new bone had grown
      into the space between the outer and inner membranes, forming the "neocortex."
      CONCLUSIONS: The resorbable polymeric implant consisting of two concentric
      perforated membranes (the tube-in-tube implant) used in combination with
      cancellous bone graft to treat segmental diaphyseal defects in sheep tibiae
      allows for the reconstitution of the "neocortex" with well-defined thickness.
      (ABSTRACT TRUNCATED)

PMID- 10206251
TI  - Schuhli augmentation of plate and screw fixation for humeral shaft fractures: a
      laboratory study.
AB  - OBJECTIVES: Schuhli locking nuts provide a mechanism to lock 4.5-millimeter bone
      screws to a standard dynamic compression plate (DCP plate). It has been proposed
      that Schuhlis can provide increased fixation stability in areas of a proximal
      cortical defect or osteopenic bone and may keep screws from loosening and backing
      out from the plate. A biomechanical study was performed to investigate the effect
      of Schuhli augmentation of a ten-hole broad DCP plate for fixation of a simulated
      humeral shaft fracture versus standard DCP plate fixation. DESIGN: Biomechanical
      cadaver study. INTERVENTION: Six pairs of cadaveric humeri from elderly
      individuals were tested in offset axial loading, torsion, and four-point bending
      to obtain load versus deformation curves and baseline mechanical properties. Each
      pair of humeri was then instrumented with a ten-hole broad DCP plate on one side
      and a DCP plate augmented with Schuhlis at each screw hole on the contralateral
      side. All screws were placed in cortical bone. The constructs were retested in
      all three modalities. The humeri were then cycled in torsion for 1,000 cycles and
      retested in all three modalities. Each humerus was then loaded to failure in
      torsion to determine the ultimate load and rotational displacement. MAIN OUTCOME
      MEASUREMENTS: Resistance to displacement was determined from the load versus
      deformation curves in each testing modality before and after cycling; these data
      were normalized to the intact values determined prior to instrumentation. Paired
      Student's t tests were performed to determine statistically significant
      differences between the two modes of fixation. RESULTS: There were no significant
      differences in stability between the two fixation techniques in all three testing
      modalities both before and after cycling. However, the Schuhli augmented
      constructs sustained significantly greater loads and rotational deformations
      prior to failure. CONCLUSIONS: In this model of humeral shaft fractures in the
      elderly, the addition of Schuhlis did not significantly change the mechanical
      stability of plate and screw fixation. However, load and angular deformation at
      failure were significantly greater in the Schuhli augmented specimens.

PMID- 10206252
TI  - Half-ring external fixation in the management of tibial plafond fractures.
AB  - OBJECTIVE: To investigate the management of tibial plafond fractures with a half
      ring external fixator using half pins. DESIGN: Prospective. SETTING: University
      teaching hospital. PATIENTS: Twenty-four patients with AO Type A or C tibial
      plafond fractures. OUTCOME MEASURES: Outcome was assessed by using standard
      criteria of time to union, incidence of infection and malunion, and incidence of
      pin-tract sepsis. Functional return was assessed by measuring hindfoot function.
      A scoring system, incorporating clinical and radiological results, was used to
      rate the results. RESULTS: When using closed or minimally open reduction
      techniques and interfragmentary screw fixation for the articular component of the
      fractures, the results of using a half-ring external fixator with half-pins were
      comparable with those of using small wire fixators. There was a 4.2 percent
      incidence of infection, and 75 percent of the patients had good or excellent
      results. CONCLUSIONS: A half-ring external fixator using half-pins produces
      results that are comparable to those obtained with small wire external fixation.
      However, the technique is easier and safer.

PMID- 10206253
TI  - Anatomical variations of the lateral femoral cutaneous nerve and the consequences
      for surgery.
AB  - PURPOSE: This two-part study was undertaken to (a) determine the course and
      variations of the lateral femoral cutaneous nerve in a cadaver study and (b)
      develop prospectively the preoperative protocol to diminish the possibility of a
      postoperative meralgia paresthetica; the latter was achieved by reviewing the
      patient series retrospectively for complaints of a lateral femoral cutaneous
      nerve (LFCN) lesion and by studying the relation of the course of the LFCN and
      meralgia paresthetica. METHODS: Anatomical studies were performed on 200 recently
      deceased patients. After exploring the LFCN from its origin to the inguinal
      region to determine its course, we classified 149 patients as "normal" and fifty
      one as abnormal. We then identified eighty-two patients who, between 1989 and
      1994, experienced LFCN lesion as a complication of pelvic surgery following an
      ilioinguinal approach. RESULTS: Thirty-seven of these patients reported altered
      sensation for several years postoperatively (minimum follow-up one year),
      including eleven patients whose complaints persisted. In five of these cases,
      symptoms prompted an eventual exploration of the nerve, and nerve entrapment was
      confirmed. Between 1994 and 1996, perioperative care intended to lessen the
      chance of future LFCN problems was administered to forty patients. Thirty-three
      patients underwent neurolysis, and seven underwent nerve transection because an
      LFCN lesion occurred during the operation. Within a twelve-month follow-up
      period, no meralgia paresthetica was noted. CONCLUSION: The practical importance
      of the present study lies in alerting the surgeon to a possible anatomical
      variation of the LFCN in about 25 percent of the patient population. It also
      confirms that the new perioperative protocol lowers the incidence of meralgia
      paresthetica.

PMID- 10206254
TI  - Effects of torsional rigidity on fracture healing: strength and mineralization in
      rat femora.
AB  - OBJECTIVE: To assess the effects of torsional rigidity and dynamization on
      fracture healing in a medullary nailed rat femoral model. STUDY DESIGN:
      Randomized study in male Wistar rats with a diaphyseal osteotomy/fracture.
      METHODS: Reamed cannulated nailing was performed in sixty rats. One group (twenty
      rats) received unlocked nails (UL group) and another group received nails with
      proximal and distal locking that was dynamized after twenty days (DL group). The
      third group was statically locked (SL group). A fourth group of twenty rats
      served as the control group. After randomization, the femurs of ten rats in each
      group at six and twelve weeks were studied clinically, radiologically, and
      biomechanically, and bone mineralization was measured by dual-energy x-ray
      absorptiometry (DEXA). RESULTS: Radiographs in two planes revealed clearly
      visible fractures at six weeks, and at twelve weeks bridging callus was apparent
      in all three treatment groups. The callus area in the UL group was significantly
      larger at six weeks than in the other groups, and at twelve weeks the UL and DL
      groups had larger callus areas than the SL group. Biomechanically, UL nails had
      reduced maximum bending load at six and twelve weeks, while DL nails had
      increased fracture energy at six weeks compared with SL nails. Bone mineral
      content and bone mineral density in the callus segment and diaphysis were
      increased with DL nails at six weeks. CONCLUSION: This animal study indicates
      that (a) interlocked nailing has a beneficial effect on bone healing and (b)
      although dynamization may have a beneficial effect on the quality of early bone
      healing, (c) dynamization does not increase the rate of bony union. The clinical
      implication is that routine early dynamization of locked femoral fractures may
      not be indicated, reserving dynamization to cases of delayed union.

PMID- 10206255
TI  - Superior gluteal artery injury during iliosacral screw placement.
AB  - Percutaneous fixation of an unstable pelvic ring injury is becoming a popular
      method of pelvic stabilization. As posterior pelvic percutaneous techniques
      become more common, the possibility of iatrogenic complications increases. This
      case report describes an injury to the superior gluteal artery during
      percutaneous iliosacral screw insertion and the treatment of this potentially
      devastating injury.

PMID- 10206256
TI  - Pseudo-dislocation of the sternoclavicular joint.
AB  - Fractures of the medial third of the clavicle are the rarest of all clavicle
      fractures. We present two cases of medial clavicle fracture nonunions that were
      initially thought to be chronic anterior sternoclavicular dislocations and
      describe the entity of pseudo-dislocation of the sternoclavicular joint. Computed
      tomography should be performed on all patients with suspected or established
      injuries of the sternoclavicular region to ensure differentiation between
      fracture and dislocation.

PMID- 10206257
TI  - Acute compartment syndrome of the triceps and deltoid.
AB  - Compartment syndrome is a condition in which the circulation and function of
      tissues within a closed space are compromised by increased pressure within that
      space. We report on the rare occurrence of compartment syndrome of the upper arm
      and deltoid in a professional power-lifter. This case stresses the importance of
      heightened awareness and expedient measures to prevent ischemic muscle necrosis
      and nerve injury.

PMID- 10206258
TI  - Irreducible fracture-dislocation of the hip: a severe injury with a poor
      prognosis.

PMID- 10206259
TI  - Urban health and household decision-making.

PMID- 10206260
TI  - Evaluation of a quantitative determination of CD4 and CD8 molecules as an
      alternative to CD4+ and CD8+ T lymphocyte counts in Africans.
AB  - In the developed word, monitoring HIV-infected patients is routinely determined
      by CD4+ T lymphocyte absolute counts. The reference procedure, flow cytometry, is
      expensive, requires sophisticated instrumentation and operators with specific
      training. Due to these limitations, CD4 counting is often unavailable in
      developing countries. The Capcellia assay is an enzyme-linked immunoassay for
      quantitative determination of CD4 and CD8 molecules. We evaluated this method in
      West Africa on blood samples collected from 39 HIV-uninfected and 44 HIV-infected
      adult subjects. CD4 concentration ranges were determined according to the
      clinical stages of the disease. We then studied the relationship between the two
      methods in the HIV-infected patients. The Spearman's rank correlation was 0.61
      (95% confidence interval: 0.38-0.76, P < 0.0001). Nevertheless, determination of
      limits of agreement revealed discrepancies between the two methods, especially
      for CD4 counts > 0.4 x 10(9)/l, which are discussed. We conclude that the
      Capcellia assay is a convenient means to determine the immunodepression level
      where flow cytometric instrumentation is unavailable, and can be complementary to
      CD4 T lymphocyte enumeration.

PMID- 10206261
TI  - Upregulation of the chemokines Rantes, MCP-1, MIP-1a and MIP-2 in early infection
      with Trypanosoma brucei brucei and inhibition by sympathetic denervation of the
      spleen.
AB  - We examined the induction of 4 chemokines during early experimental African
      trypanosomiasis using in situ hybridization and immunocytochemistry. mRNA
      expression and protein production of Rantes, MCP-1, MIP-1a and MIP-2 were studied
      in splenocytes obtained at 0 h, 4 h and 12 h post-infection. Splenic denervation
      was performed to study the role of the central nervous system in early infection.
      The mRNA for Rantes increased at 4 h and declined at 12 h, but the protein level
      was high at both time-points. MCP-1 and MIP-la had elevated mRNA and protein
      levels at 12 h post-infection. MIP-2 mRNA was high at both 4 h and 12 h, but the
      protein level was only increased at 12 h. Splenic denervation, but not sham
      operation, suppressed these responses. The upregulation of these chemokines
      during very early infection suggests a chemokine role in the developing
      immunopathology The sympathetic nervous system may, however, participate in
      modulation of such early immune responses.

PMID- 10206262
TI  - Anti-filarial IgG4 in men and women living in Brugia malayi-endemic areas.
AB  - To assess whether antifilarial IgG4 can be used to study various epidemiological
      facets of filarial infections, we studied this isotype in 238 individuals
      resident in areas endemic for brugian filariasis, focusing on the differences
      between men and women. In the study area, the prevalence of microfilariae was
      6.7% and the prevalence of antifilarial IgG4 was 49.2%. All microfilariae
      carriers were positive for antifilarial IgG4, whereas a proportion of the endemic
      normals (94/208) and clephantiasis patients (7/14) had IgG4 antibodies to
      filarial antigens. Data were analysed as a function of gender in distinct
      clinical groups and stratified for age. The prevalence of microfilariae was
      higher in males in all age groups, as reflected in significantly higher
      antifilarial IgG4 antibody levels compared to females. The prevalence of IgG4
      increased to reach a plateau at the age of 30 years in both males and females.
      These results indicate that antifilarial IgG4 antibodies can reflect the
      differences in the extent of infection in males and females as measured by
      microfilarial counts, and that this parameter can be used for epidemiological
      assessments of filarial infection.

PMID- 10206264
TI  - Towards a kala azar risk map for Sudan: mapping the potential distribution of
      Phlebotomus orientalis using digital data of environmental variables.
AB  - The need to define the geographical distribution of Phlebotomus orientalis
      results from its importance as the dominant vector of kala azar (visceral
      Iceishmaniasis) in Sudan. Recent epidermics of this disease in southern and
      eastern Sudan caused an estimated 100000 deaths and have renewed the impetus for
      defining the ecological boundaries of the vector. This information is an
      essential prerequisite to the production of a risk map for kala azar. This study
      uses data on the presence and absence of P. orientalis from 44 collecting sites
      across the central belt of Sudan. A logistic regression model was used to
      estimate the probability of the presence of P. orientalis at each collecting site
      as a function of climatic and environmental variables (rainfall; temperature;
      altitude; soil type and the satellite-derived environmental proxies - Normalized
      Difference Vegetation Index and Land Surface Temperature). The logistic
      regression model indicates mean annual maximum daily temperature and soil type as
      the most important ecological determinants of P. orientalis distribution. An
      initial risk map was created in a raster-based geographical information system
      which delineates the area where P. orientalis may occur. This map was then
      refined using a mask layer indicating the known rainfall-based boundaries of the
      distribution of Acacia-Balanites woodland - a woodland type known to be
      associated with the distribution of this vector. The predictive performance of
      the risk map is discussed.

PMID- 10206263
TI  - Comparison of serological and parasitological assessments of Onchocerca volvulus
      transmission after 7 years of mass ivermectin treatment in Mexico.
AB  - OBJECTIVE AND METHOD: To compare the utility of an ELISA using 3 recombinant
      antigens with that of the skin biopsy to estimate incidence of infections in a
      sentinel cohort of individuals living in an endemic community in southern Mexico
      during a set of 11 subsequent ivermectin treatments. RESULTS: The apparent
      community prevalence of infection and microfilarial skin infection before and
      after 11 treatments with ivermectin plus nodulectomy were 78% and 13%, and 0.68
      mf/mg and 0.04 mf/mg, respectively, as measured by skin biopsy. Of a group of 286
      individuals participating in all surveys, a sentinel cohort of 42 mf and
      serologically negative individuals had been followed since 1994. The annual
      percentage of individuals becoming positive in this cohort was 24% (10/42), 28%
      (9/33), 0%, and 4.3% (1/23) in 1995, 1996, 1997 and 1998, respectively. Likewise,
      the incidence in children 5 years and under (n = 13) within this sentinel cohort
      was 15% (2/13), 18% (2/11), 0% and 11% (1/9), respectively. All individuals
      became positive to both tests simultaneously, indicating that seroconversion
      assessed infection incidence as accurately as skin biopsy in the sentinel group.
      CONCLUSION: Incidence monitoring of a sentinel cohort provides an estimation of
      the parasite transmission in the community; it is less costly than massive
      sampling, and a finger prick blood test might be more acceptable in some
      communities.

PMID- 10206265
TI  - Syndromic management of sexually transmitted diseases: is it rational or
      scientific?
AB  - Control of sexually transmitted diseases improves the reproductive and sexual
      health of afflicted individuals and lowers the community burden of HIV.
      Preventing STDs or their complications requires health education, condom
      promotion and effective case management. Clinical diagnosis is frequently
      incorrect while laboratory-confirmed aetiological diagnosis is expensive. In
      resource-poor countries which lack trained personnel and laboratory facilities,
      syndromic management remains a rational approach to STD care. Although the
      approach is simplistic in design, its successful implementation requires regular
      monitoring and evaluation of protocols as well as supervision and training of
      clinicians.

PMID- 10206266
TI  - How useful are anthropometric, clinical and dietary measurements of nutritional
      status as predictors of morbidity of young children in central Africa?
AB  - OBJECTIVE: To identify useful predictors of morbidity of young children in
      central Africa. METHOD: Population-based follow-up study in Northern Kivu, Congo,
      of 842 children under two years of age who completed weekly follow-up interviews
      and health examinations during three months. Main outcome measures were crude and
      adjusted effects of summary measures of nutritional status on one-month
      cumulative incidence of malaria, respiratory illness, and diarrhoea. RESULTS:
      Anthropometric indicators appeared to perform badly in predicting morbidity. In
      contrast, non-anthropometric variables such as growth as judged by the caretaker,
      child's diet at the time of examination, and occurrence of disease in the month
      preceding the interval of observation were useful. CONCLUSIONS: In the context of
      the 'Sick Child Initiative', simple tests and diagnostic tools to improve quality
      of both prevention and cure in first-level facilities need to be identified.
      Focusing on non-anthropometric indicators should be encouraged to offer a
      comprehensive appraisal of health status to all children.

PMID- 10206267
TI  - Host haematological factors influencing the transmission of Plasmodium falciparum
      gametocytes to Anopheles gambiae s.s. mosquitoes.
AB  - We investigated the relationship between selected host haematological and
      parasitological parameters and the density and infectivity of Plasmodium
      falciparum gametocytes. 143 individuals (age range 1-62 years) attending an
      outpatient clinic in Farafenni, The Gambia, who had peripheral blood
      gametocytaemia were recruited (mean gametocyte density 123.7/microl, range 5
      17,000/microl). Of the parameters measured, packed cell volume (PCV),
      reticulocyte count (RetC) and lymphocyte count (LyC) were significantly
      associated with gametocyte density (r = - 0.17, P < 0.05; r = 0.21, P < 0.01; r =
      0.18, P < 0.05, respectively). Data from membrane feeding experiments in which 15
      or more mosquitoes were dissected showed that 60.7% (53/87) of gametocyte
      carriers infected one or more mosquitoes. Gametocyte density was strongly
      correlated with transmission success (TS) (r = 0.3, P < 0.005) and, in successful
      infections, with both mosquito prevalence (MP) (r = 0.36, P < 0.005) and mean
      oocyst burden (MOB) (r = 0.65, P < 0.0001). None of the other factors measured
      were significantly associated with any of these indices in bivariate analysis.
      Regression modelling showed that both gametocyte density and PCV were positively
      associated with gametocyte carrier infectivity to mosquitoes (LRchi2 = 100.7 and
      47.2, respectively) and, in successful infections, with MOB (beta = 0.16, t =
      4.9, P < 0.001; beta = 0.02, t = 2.3, P < 0.05, respectively). The positive
      association with PCV suggests that blood meal quality influences infection
      probably as a nutritional requirement, however, as this effect was most apparent
      at high gametocyte densities, its epidemiological significance is questionable.
      Though the haematological parameters associated with gametocyte density are a
      direct consequence of asexual infection, they may also represent an adaptive
      mechanism for optimization of sexual stage development.

PMID- 10206268
TI  - Control of malaria vectors: cost analysis in a province of northern Vietnam.
AB  - The cost of permethrin-treated bednets (50% EC; 0.2 g/m2, 2 rounds per year) was
      compared to the cost of residual spraying with lambdacyhalothrin 10% WP (0.03
      g/m2, once yearly) in Hoa Binh, a mountainous province in northern Vietnam.
      Calculations of the amounts of insecticides needed were based on national
      guidelines, on data from a cross-sectional survey and on district activity
      reports. The actual cost of insecticide required per person per year was lower
      for impregnation (US$ 0.26) than for spraying (US$ 0.36), but the difference was
      smaller than expected. The total cost for impregnated bednets per person per year
      amounted to US$ 0.90 compared to USS 0.47 for spraying. The determining factor
      was the cost of the net, amounting to US$ 0.58 per person per year, assuming a 5
      year life of the net. Other material (excluding nets), labour and transport
      combined, accounted for only 17% of the impregnation cost and 23% of spraying
      expenses. However, for the National Malaria Control Programme of Vietnam, the
      cost per person per year for impregnated bednets amounted to US$ 0.32 only,
      because the vast majority of nets are bought by the population. For spraying, the
      programme had to bear the entire cost.

PMID- 10206269
TI  - Rapid economic growth and 'the four Ds' of disruption, deprivation, disease and
      death: public health lessons from nineteenth-century Britain for twenty-first
      century China?
AB  - Rapid economic growth has always entailed serious disruption: environmental,
      ideological, and political. As a result the relationship between economic growth
      and public health is complex since such disruption always threatens to spill over
      into deprivation, disease and death. The populations of most current high-income,
      high-life expectancy countries of 'the West' endured several decades of severely
      compromised health when they first experienced industrialization in the last
      century Although health technologies have moved on, the social, administrative
      and political disruption accompanying economic growth can still impede the
      delivery of health improvements. The case history of 19th-century laissez-faire
      Britain is explored in some detail to demonstrate the importance of these social
      and political forces, particularly the relative vigour and participatory nature
      of local government, linking to recent work on the importance of social capital
      in development. For a country like China today, paradoxically, there is nothing
      that needs such careful planning as a 'free market' economy.

PMID- 10206271
TI  - In pursuit of excellence for patients with cancer: the Scottish Cancer Therapy
      Network model.
AB  - The Scottish Cancer Therapy Network (SCTN) was created against a background of
      rising concerns about perceived variation in the quality of care available to
      patients with cancer. SCTN has established itself as a major organization with
      the necessary recognition and infrastructure to provide leadership, support and
      impetus in the field of clinical guidelines, clinical audit and clinical trials
      of cancer therapy in Scotland. Since being formed in 1993, SCTN has been
      instrumental in the development of three evidence-based, clinical guidelines and
      in the completion of detailed, national, retrospective audits of the treatment of
      five major tumour sites. The infrastructure has been used successfully to support
      and encourage trial participation. Challenges for the future are a re-orientation
      towards prospective audit, widening the constituency and sense of ownership of
      SCTN as a resource for practising clinicians, and further increasing recruitment
      into clinical trials.

PMID- 10206270
TI  - Making the most of rodent tumour systems in cancer drug discovery.

PMID- 10206272
TI  - Determination of an optimal dosing regimen for aspirin chemoprevention of 1,2
      dimethylhydrazine-induced colon tumours in rats.
AB  - In order to establish an optimal timing and duration of aspirin treatment in the
      chemoprevention of 1,2-dimethylhydrazine (DMH)-induced colon cancer in rats,
      colon tumours were induced using an established protocol and aspirin was given in
      the diet at 500 p.p.m. during various stages of colon carcinogenesis. Results
      indicate that only aspirin treatment throughout the entire carcinogenic period
      significantly reduced tumour incidence and volume whereas intermittent aspirin
      dosing increased tumour number and/or volume, suggesting that aspirin must be
      used for an extended period in order to gain any chemopreventive benefit.

PMID- 10206273
TI  - Overexpression of Bcl-2 enhances metastatic potential of human bladder cancer
      cells.
AB  - We investigated the effect of Bcl-2 expression on the metastatic process of
      bladder cancer cells by using the Bcl-2-transfected human bladder cancer cell
      lines (KoTCC-1/BH) and the control vector only-transfected cell line (KoTCC-1/C),
      which were generated in our previous study (Miyake et al (1998) Oncogene 16: 933
      934). When they were injected intravenously into athymic nude mice, KoTCC-1/BH
      formed more than three times as many tumour nodules in the lungs as did KoTCC
      1/C. In addition, tumour progression, including lymph node metastasis and
      haemorrhagic ascites, was observed to be more advanced after the implantation of
      KoTCC-1/BH cells into the bladder wall of nude mice than after implantation of
      KoTCC-1/C cells. These enhanced malignant progression of KoTCC-1/BH cells were
      well correlated with anti-apoptotic activity under anchorage-independent
      conditions in in vitro experimental models. In contrast, there were no
      significant differences among these cell lines in their growth rates both in
      vitro and in vivo, invasive ability and cell motility. These findings suggest
      that, if it is overexpressed, Bcl-2 prolongs cell survival under unfavourable
      conditions encountered in the metastatic process, resulting in the enhanced
      metastatic potential of bladder cancer.

PMID- 10206274
TI  - Radiation-induced G1 arrest is not defective in fibroblasts from Li-Fraumeni
      families without TP53 mutations.
AB  - Radiation-induced G1 arrest was studied in four classes of early passage skin
      fibroblasts comprising 12 normals, 12 heterozygous (mut/wt) TP53 mutation
      carriers, two homozygous (mut/-) TP53 mutation-carriers and 16 strains from nine
      Li-Fraumeni syndrome or Li-Fraumeni-like families in which no TP53 mutation has
      been found, despite sequencing of all exons, exon-intron boundaries, 3' and 5'
      untranslated regions and promoter regions. In an assay of p53 allelic expression
      in yeast, cDNAs from these non-mutation strains behaved as wild-type p53. Using
      two different assays, we found G1 arrest was reduced in heterozygous strains with
      mis-sense mutations and one truncation mutation, when compared to the range
      established for the normal cells. Heterozygous strains with mutations at splice
      sites behaved like normal cells, whilst homozygous (mut/-) strains showed either
      extremely reduced, or no, arrest. Strains from all nine non-mutation families
      gave responses within the normal range. Exceptions to the previously reported
      inverse correlation between G1 arrest and clonogenic radiation resistance were
      observed, indicating that these phenotypes are not strictly interdependent.

PMID- 10206275
TI  - In vitro assessment of Lipiodol-targeted radiotherapy for liver and colorectal
      cancer cell lines.
AB  - Intra-arterial Lipiodol has been used to deliver targeted therapies to primary,
      and some metastatic, liver cancers. Targeted radiotherapy has been used by
      substituting the iodine in Lipiodol with 131Iodine (131I). Early clinical results
      are encouraging, but the variable response may partly depend on local
      pharmacokinetics. This study evaluated the in vitro cytotoxic effects of 131I
      Lipiodol on human hepatocellular carcinoma (Hep-G2), human colorectal metastatic
      cancer (SW620), human colorectal hepatic cancer (LoVo) and human umbilical vein
      endothelial cells (HUVEC) cell lines. The cell cultures were exposed to 131I
      Lipiodol for 48 h, following which cell counts and viability were assessed by
      haemocytometer, S-Rhodamine uptake and radioactivity assay. The effect of
      exposure to control Lipiodol, 131I-Lipiodol and 131I alone was evaluated. 131I
      Lipiodol was cytotoxic against all the cancer cell lines but not against the non
      malignant (HUVEC) cell line. The cytotoxicity effects were very similar in all
      the cancer cell lines. There were no cytotoxic effects following exposure to
      plain 131I in any of the cell lines (malignant and non-malignant). A similar
      trend was seen with radioactivity counts using a gamma counter. The cytotoxic
      effect of 131I-Lipiodol had a graded effect with an increase in cytotoxicity
      following the increase in the radioactive dose. This study showed that there was
      a marked cytotoxic effect by 131I-Lipiodol on all the cancer cell lines. There
      was no difference between the controls and the 131Iodine. This suggests that
      effective 131I-Lipiodol targeted therapy is dependent on the uptake and retention
      of Lipiodol by malignant cells.

PMID- 10206276
TI  - In vivo efficacy of XR9051, a potent modulator of P-glycoprotein mediated
      multidrug resistance.
AB  - Overexpression of P-glycoprotein (P-gp) is a potential cause of multidrug
      resistance (MDR) in tumours. We have previously reported that XR9051 (N-(4-(2
      (6,7-dimethoxy-1,2,3,4-tetrahydro-2-isoquinolyl)ethyl)phe nyl)-3-((3Z,6Z)-6
      benzylidene-1-methyl-2,5-dioxo-3-pipera zinylidene)methylbenzamide) is a potent
      and specific inhibitor of P-gp, which reverses drug resistance in several murine
      and human MDR cell lines. In this study we have evaluated the in vivo efficacy of
      this novel modulator in a panel of murine and human tumour models and examined
      its pharmacokinetic profile. Efficacy studies in mice bearing MDR syngeneic
      tumours (P388/DX Johnson, MC26) or human tumour xenografts (A2780AD, CH1/DOXr,
      H69/LX) demonstrated that co-administration of XR9051 significantly potentiated
      the anti-tumour activity of a range of cytotoxic drugs. This modulatory activity
      was observed following parenteral and oral co-administration of XR9051. In
      addition, the combination schedules were well-tolerated. Following intravenous
      administration in mice, XR9051 is rapidly distributed and accumulates in tumours
      and other tissues. In addition, the compound is well-absorbed after oral
      administration. These data suggest that XR9051 has the potential for reversing
      clinical MDR mediated by P-glycoprotien.

PMID- 10206277
TI  - DT-diaphorase activity in NSCLC and SCLC cell lines: a role for fos/jun
      regulation.
AB  - To assess the potential differential lung tumour expression of NAD(P)H:quinone
      reductase (NQO1), the human (h) NQO1 promoter was characterized in gene transfer
      studies. A deletion panel of 5' flanking hNQO1 promoter constructs was made and
      tested in transient transfection assays in NSCLC and SCLC cell lines. The largest
      hNQO1 construct (-1539/+115) containing the antioxidant response element (ARE),
      exhibited robust levels of reporter activity in the NSCLC (H460, H520, and A549)
      cell lines and expression was over 12 to 77-fold higher than the minimal (
      259/+115) promoter construct. In contrast, there was little difference in
      promoter activity between the largest and minimal promoter construct in the SCLC
      (H146, H82 and H187) cell lines. Deletion of the sites for NFkappaB and AP-2 and
      the XRE did not significantly affect hNQO1 promoter activity in either the NSCLC
      or SCLC cell lines. Robust promoter activity in NSCLC lines was mediated by a 359
      bp segment of the proximal promoter that contained a canonical AP-1 binding site,
      TGACTCAG, within the ARE. Gel supershift assays with various specific Fos/Jun
      antibodies identified Fra1, Fra2 and Jun B binding activity in NSCLC cells to a
      promoter fragment (-477 to -438) spanning the AP-1 site, whereas SCLC do not
      appear to express functional Fra or Jun B. These results suggest a possible role
      for AP-1 activity in the differential expression of hNQO1 in NSCLC.

PMID- 10206278
TI  - Caspase I-related protease inhibition retards the execution of okadaic acid- and
      camptothecin-induced apoptosis and PAI-2 cleavage, but not commitment to cell
      death in HL-60 cells.
AB  - We have previously reported that the putative cytoprotective protease inhibitor,
      plasminogen activator inhibitor type 2 (PAI-2), is specifically cleaved during
      okadaic acid-induced apoptosis in a myeloid leukaemic cell line (Br J Cancer
      (1994) 70: 834-840). HL-60 cells exposed to okadaic acid and camptothecin
      underwent morphological and biochemical changes typical of apoptosis, including
      internucleosomal DNA fragmentation and PAI-2 cleavage. Significant endogenous PAI
      2 cleavage was observed 9 h after exposure to okadaic acid; thus correlating with
      other signs of macromolecular degradation, like internucleosomal DNA
      fragmentation. In camptothecin-treated cells, PAI-2 cleavage was an early event,
      detectable after 2 h of treatment, and preceding internucleosomal DNA
      fragmentation. The caspase I selective protease inhibitor, YVAD-cmk, inhibited
      internucleosomal DNA fragmentation and PAI-2 cleavage of okadaic acid and
      camptothecin-induced apoptotic cells. YVAD-cmk rather sensitively and non
      toxically inhibited camptothecin-induced morphology, but not okadaic acid-induced
      morphology. In in vitro experiments recombinant PAI-2 was not found to be a
      substrate for caspase I. The results suggest that caspase I selective protease
      inhibition could antagonize parameters coupled to the execution phase of okadaic
      acid- and camptothecin-induced apoptosis, but not the commitment to cell death.

PMID- 10206279
TI  - A novel class of lipophilic quinazoline-based folic acid analogues: cytotoxic
      agents with a folate-independent locus.
AB  - Three lipophilic quinazoline-based aminomethyl pyridine compounds, which differ
      only in the position of the nitrogen in their pyridine ring, are described.
      CB300179 (2-pyridine), CB300189 (4-pyridine) and CB30865 (3-pyridine) all
      inhibited isolated mammalian TS with IC50 values of 508, 250 and 156 nM
      respectively. CB30865 was the most potent growth inhibitory agent (IC50 values in
      the range 1-100 nM for several mouse and human cell types). CB300179 and CB300189
      were active in the micromolar range. Against W1L2 cells, CB300179 and CB300189
      demonstrated reduced potency in the presence of exogenous thymidine (dThd), and
      against a W1L2:C1 TS overproducing cell line. In contrast, CB30865 retained
      activity in these systems. Furthermore, combinations of precursors and end
      products of folate metabolism, e.g. dThd/hypoxanthine (HX) or leucovorin (LV),
      did not prevent activity. CB30865 did not interfere with the incorporation of
      tritiated dThd, uridine or leucine after 4 h. A cell line was raised with
      acquired resistance to CB30865 (W1L2:R865; > 200-fold), which was not cross
      resistant to CB300179 or CB300189. In addition, W1L2:R865 cells were as sensitive
      as parental cells to agents from all the major chemotherapeutic drug classes.
      CB300179 and CB300189 induced an S phase accumulation (preventable by co
      administration of dThd). No cell cycle redistribution was observed following
      exposure (4-48 h) to an equitoxic concentration of CB30865. In the NCI anticancer
      drug-discovery screen, CB30865 displayed a pattern of activity which was not
      consistent with known anti-tumour agents. These data suggest that CB30865
      represents a class of potent potential anti-tumour agents with a novel mechanism
      of action.

PMID- 10206280
TI  - Analysis of acute vascular damage after photodynamic therapy using benzoporphyrin
      derivative (BPD).
AB  - Benzoporphyrin derivative monoacid ring A (BPD-MA, verteporfin) is currently
      under investigation as a photosensitizer for photodynamic therapy (PDT). Since
      BPD exhibits rapid pharmacokinetics in plasma and tissues, we assessed damage to
      tumour and muscle microvasculature when light treatment for PDT was given at
      short times after injection of photosensitizer. Groups of rats with
      chondrosarcoma were given 2 mg kg(-1) of BPD intravenously 5 min to 180 min
      before light treatment of 150 J cm(-2) 690 nm. Vascular response was monitored
      using intravital microscopy and tumour cure was monitored by following regrowth
      over 42 days. For treatment at 5 or 30 min after BPD injection, blood flow stasis
      was limited to tumour microvasculature with lesser response in the surrounding
      normal microvasculature, indicating selective targeting for damage. No acute
      changes were observed in vessels when light was given 180 min after BPD
      injection. Tumour regression after light treatment occurred in all animals given
      PDT with BPD. Long-term tumour regression was greater in animals treated 5 min
      after BPD injection and least in animals given treatment 180 min after drug
      injection. The correlation between the timing for vascular damage and cure
      implies that blood flow stasis plays a significant role in PDT-induced tumour
      destruction.

PMID- 10206281
TI  - Carbogen-induced changes in rat mammary tumour oxygenation reported by near
      infrared spectroscopy.
AB  - We have evaluated the ability of steady-state, radially-resolved, broad-band near
      infrared diffuse reflectance spectroscopy to measure carbogen-induced changes in
      haemoglobin oxygen saturation (SO2) and total haemoglobin concentration in a rat
      R3230 mammary adenocarcinoma model in vivo. Detectable shifts toward higher
      saturations were evident in all tumours (n = 16) immediately after the onset of
      carbogen breathing. The SO2 reached a new equilibrium within 1 min and remained
      approximately constant during 200-300 s of administration. The return to baseline
      saturation was more gradual when carbogen delivery was stopped. The degree to
      which carbogen increased SO2 was variable among tumours, with a tendency for
      tumours with lower initial SO2 to exhibit larger changes. Tumour haemoglobin
      concentrations at the time of peak enhancement were also variable. In the
      majority of cases, haemoglobin concentration decreased in response to carbogen,
      indicating that increased tumour blood volume was not responsible for the
      observed elevation in SO2. We observed no apparent relationship between the
      extent of the change in tumour haemoglobin concentration and the magnitude of the
      change in the saturation. Near infrared diffuse reflectance spectroscopy provides
      a rapid, non-invasive means of monitoring spatially averaged changes in tumour
      haemoglobin oxygen saturation induced by oxygen modifiers.

PMID- 10206282
TI  - Quantification of longitudinal tissue pO2 gradients in window chamber tumours:
      impact on tumour hypoxia.
AB  - We previously reported that the arteriolar input in window chamber tumours is
      limited in number and is constrained to enter the tumour from one surface, and
      that the pO2 of tumour arterioles is lower than in comparable arterioles of
      normal tissues. On average, the vascular pO2 in vessels of the upper surface of
      these tumours is lower than the pO2 of vessels on the fascial side, suggesting
      that there may be steep vascular longitudinal gradients (defined as the decline
      in vascular pO2 along the afferent path of blood flow) that contribute to
      vascular hypoxia on the upper surface of the tumours. However, we have not
      previously measured tissue pO2 on both surfaces of these chambers in the same
      tumour. In this report, we investigated the hypothesis that the anatomical
      constraint of arteriolar supply from one side of the tumour results in
      longitudinal gradients in pO2 sufficient in magnitude to create vascular hypoxia
      in tumours grown in dorsal flap window chambers. Fischer-344 rats had dorsal flap
      window chambers implanted in the skin fold with simultaneous transplantation of
      the R3230AC tumour. Tumours were studied at 9-11 days after transplantation, at a
      diameter of 3-4 mm; the tissue thickness was 200 microm. For magnetic resonance
      microscopic imaging, gadolinium DTPA bovine serum albumin (BSA-DTPA-Gd) complex
      was injected i.v., followed by fixation in 10% formalin and removal from the
      animal. The sample was imaged at 9.4 T, yielding voxel sizes of 40 microm.
      Intravital microscopy was used to visualize the position and number of arterioles
      entering window chamber tumour preparations. Phosphorescence life time imaging
      (PLI) was used to measure vascular pO2. Blue and green light excitations of the
      upper and lower surfaces of window chambers were made (penetration depth of light
      approximately 50 vs >200 microm respectively). Arteriolar input into window
      chamber tumours was limited to 1 or 2 vessels, and appeared to be constrained to
      the fascial surface upon which the tumour grows. PLI of the tumour surface
      indicated greater hypoxia with blue compared with green light excitation (P <
      0.03 for 10th and 25th percentiles and for per cent pixels < 10 mmHg). In
      contrast, illumination of the fascial surface with blue light indicated less
      hypoxia compared with illumination of the tumour surface (P < 0.05 for 10th and
      25th percentiles and for per cent pixels < 10 mmHg). There was no significant
      difference in pO2 distributions for blue and green light excitation from the
      fascial surface nor for green light excitation when viewed from either surface.
      The PLI data demonstrates that the upper surface of the tumour is more hypoxic
      because blue light excitation yields lower pO2 values than green light
      excitation. This is further verified in the subset of chambers in which blue
      light excitation of the fascial surface showed higher pO2 distributions compared
      with the tumour surface. These results suggest that there are steep longitudinal
      gradients in vascular pO2 in this tumour model that are created by the limited
      number and orientation of the arterioles. This contributes to tumour hypoxia.
      Arteriolar supply is often limited in other tumours as well, suggesting that this
      may represent another cause for tumour hypoxia. This report is the first direct
      demonstration that longitudinal oxygen gradients actually lead to hypoxia in
      tumours.

PMID- 10206283
TI  - Overexpression of metastasis-associated MTA1 mRNA in invasive oesophageal
      carcinomas.
AB  - The MTA1 gene is a recently identified novel candidate breast cancer metastasis
      associated gene which has been implicated in the signal transduction or
      regulation of gene expression. We examined the mRNA expression levels of the
      MTA1, the human homologue of the rat mta1 gene in 47 surgically resected
      oesophageal squamous cell carcinomas by quantitative reverse transcription
      polymerase chain reaction. The relative overexpression of MTA1 mRNA
      (tumour/normal ratio > or = 2) was observed in 16 out of 47 (34.0%) oesophageal
      carcinomas. Oesophageal tumours overexpressing MTA1 mRNA (T/N ratio > or = 2)
      showed significantly higher frequencies of adventitial invasion (P < 0.05) and
      lymph node metastasis (P < 0.05), and tended to have a higher rate of lymphatic
      involvement than the remaining tumours. Thus, the data suggest that the MTA1 gene
      might play an important role in invasion and metastasis of oesophageal
      carcinomas.

PMID- 10206285
TI  - Prognostic value of nuclear morphometry in patients with TNM stage T1 ovarian
      clear cell adenocarcinoma.
AB  - In 40 patients with TNM stage T1 ovarian clear cell adenocarcinoma, we used
      nuclear morphometry to study the relations among morphometric variables, clinical
      prognostic factors and outcome. The presence of one or more giant nuclear cells
      was positively associated with death (OR = 10.6, P = 0.02) and tended to be
      associated with disease recurrence (OR = 5.1, P = 0.07). Nuclear irregularity
      (expressed in terms of the nuclear roundness factor) was positively associated
      with both death (OR = 8.6, P = 0.02) and disease recurrence (OR = 8.2, P = 0.02).
      A combination of giant nuclear cell presence or nuclear irregularity proved to be
      a useful prognostic indicator, with a sensitivity and specificity of 83% and 71%
      in the prediction of death, and 75% and 71% in the prediction of disease
      recurrence. Patients' age and substage were of no prognostic value. We conclude
      that the nuclear morphometric characteristics, especially the presence of giant
      nuclear cells and nuclear irregularity, may be useful in predicting outcome in
      patients with early stage ovarian clear cell adenocarcinoma.

PMID- 10206286
TI  - Prognostic impact of in vivo soluble cell adhesion molecules in metastatic renal
      cell carcinoma.
AB  - The purpose of the study was to determine prognostic significance of pretreatment
      serum levels of different molecules involved in cell to cell interactions along
      with other clinical parameters in patients with metastatic renal cell carcinoma.
      sICAM-1, sVCAM-1 and sELAM-1 serum levels were determined by ELISA assays in sera
      from 99 patients with histologically confirmed progressive metastatic renal cell
      carcinoma prior to initiation of systemic therapy. Kaplan-Meier survival
      analysis, log-rank statistics and two-proportional Cox regression analyses were
      employed to identify risk factors and to demonstrate statistical independence. In
      univariate analyses, the following pretreatment risk factors could be identified:
      serum sICAM-1 level > 360 ng ml(-1), erythrocyte sedimentation rate > 70 mm h(
      1), serum C-reactive protein level > 8 mg l(-1), serum lactic dehydrogenase level
      > 240 U/l and neutrophil count > 6000 microl(-1). Multivariate analyses
      demonstrated statistical independence for serum sICAM-1 level, erythrocyte
      sedimentation rate (ESR) and serum C-reactive protein (CRP) level as pretreatment
      predictors of overall patient survival. The prognostic significance of sICAM-1
      might indicate a role of this molecule for tumour progression, potentially in
      association with the abrogation of anti-tumour immune responses. The possibility
      of defining a pretreatment risk model based on sICAM-1 level, ESR and CRP also
      warrants further investigation, with regard to a possible linkage between acute
      phase proteins and sICAM-1 levels.

PMID- 10206284
TI  - Prognostic value of DNA flow cytometry in stomach cancer: a 5-year prospective
      study.
AB  - The role of DNA flow cytometry in the prediction of prognosis for patients with
      stomach cancer remains to be defined. Thus we studied prospectively the role of
      DNA flow cytometry as a prognosis indicator in stomach cancer patients in a high
      incidence area. Between November 1990 and December 1992, primary stomach cancer
      tissues were obtained from the surgical specimens from 217 patients (148 male, 69
      female). DNA flow cytometric analyses of DNA ploidy and S-phase fraction were
      performed and the results were correlated with patient survival. The median age
      of the patients was 55 years (range 24-78). Aneuploid cell population was found
      in 114 of 217 samples (53%). Tumour S-phase fraction was obtained in 96 of 103
      diploid tumours (93%) and 61 of 114 aneuploid tumours (54%). After median follow
      up of 66.1 months, the patients with tumours with an S-phase fraction over 17%
      had significantly worse survival rates than patients with tumours with S-phase
      fractions of lower than 8% or 8-17% (45% vs 59% and 63% of patients surviving, P
      = 0.007). Tumour ploidy status did not correlate with patient survival.
      Multivariate analyses showed that the TNM stage remained the most important
      prognostic indicator. The tumour S-phase fraction was also an independent
      prognostic indicator (relative risk 2.300, 95% CI, 1.252-4.223). Tumour S-phase
      fraction obtained by DNA flow cytometry is an independent prognostic indicator
      for the survival of the patients with stomach cancer.

PMID- 10206288
TI  - Modelling the effects of standard prognostic factors in node-positive breast
      cancer. German Breast Cancer Study Group (GBSG).
AB  - Prognostic models that predict the clinical course of a breast cancer patient are
      important in oncology. We propose an approach to constructing such models based
      on fractional polynomials in which useful transformations of the continuous
      factors are determined. The idea may be applied with all types of regression
      model, including Cox regression, the method of choice for survival-time data. We
      analyse a prospective study of node-positive breast cancer. Seven standard
      prognostic factors--age, menopausal status, tumour size, tumour grade, number of
      positive lymph nodes, progesterone and oestrogen receptor concentrations--were
      investigated in 686 patients, of whom 299 had an event for recurrence-free
      survival and 171 died. We determine a final model with transformations of
      prognostic factors and compare it with the more traditional approaches using
      categorized variables or assuming a straight line relationship. We conclude that
      analysis using fractional polynomials can extract important prognostic
      information which the traditional approaches may miss.

PMID- 10206287
TI  - Prognostic significance of urokinase (uPA) and its inhibitor PAI-1 for survival
      in advanced ovarian carcinoma stage FIGO IIIc.
AB  - Strong evidence has accumulated on the prognostic value of tumour-associated
      proteolytic factors in patients afflicted with solid malignant tumours, including
      advanced ovarian cancer. We evaluated the prognostic impact of the protease
      urokinase plasminogen activator (uPA) and its inhibitor PAI-1 on overall survival
      in patients with advanced ovarian cancer stage FIGO IIIc in order to select
      patients at risk. uPA and PAI-1 antigen were determined by ELISA in primary
      tumour tissue extracts of 86 ovarian cancer patients FIGO stage IIIc enrolled in
      a prospective study. Univariate and multivariate analyses were performed using
      the Cox proportional hazard model. The time-varying coefficient model of Gray was
      used to assess the time-dependent strength of prognostic factors tumour mass, uPA
      and PAI-1 on overall survival. In all patients, uPA and PAI-1 (optimized cut-offs
      of 2.0 and 27.5 ng mg(-1) protein respectively), in addition to the traditional
      prognostic parameters of residual tumour mass, nodal status, grading and ascites
      volume, were of prognostic significance in univariate analysis for overall
      survival. Even in patients with residual tumour mass (n = 43), the statistically
      independent prognostic impact of PAI-1 persisted, allowing further discrimination
      between low- and high-risk patients. In multivariate analysis, residual tumour
      mass (P < 0.001, relative risk (RR) 4.5), PAI-1 (P < 0.001; RR 3.1) and nodal
      status (P = 0.022, RR 2.6) turned out to be strong, statistically independent
      prognostic parameters. Evaluation of the time-dependent prognostic impact of
      residual tumour mass and PAI-1 on overall survival (n = 86, 50 months) revealed
      that the prognostic power of these factors increased with time. In patients with
      advanced ovarian cancer, both residual tumour mass and PAI-1 are statistically
      independent strong prognostic factors. Even within patient subgroups with or
      without residual tumour mass, PAI-1 allowed selection of patients at risk who
      might benefit from individualized therapy protocols.

PMID- 10206289
TI  - Ovarian cysts in women receiving tamoxifen for breast cancer.
AB  - Tamoxifen is a nonsteroidal anti-oestrogen with gynaecological side-effects. Only
      recently, ovarian cyst formation during tamoxifen treatment has been reported.
      The present study aimed to evaluate patient-related parameters that determine
      ovarian cyst formation in women using tamoxifen for breast cancer. A cross
      sectional study was performed in 142 breast cancer patients using tamoxifen.
      Forty-five patients were also examined prior to tamoxifen treatment.
      Gynaecological assessment, transvaginal ultrasonography (TVU) and serum
      oestradiol (E2) and follicle stimulating hormone (FSH) analysis were performed.
      Follow-up assessments were performed twice a year. Uni- or bilateral ovarian
      cysts were detected by TVU in 24 tamoxifen-using patients and in one patient
      before tamoxifen treatment. Multiple regression analysis showed that cyst
      development is related (multiple R = 0.73) to high E2 (P < 0.001), younger age (P
      < 0.001) and absence of high-dose chemotherapy (P = 0.007). Patients with ovarian
      cysts had higher serum E2 levels compared to patients without cysts (1.95 vs 0.05
      nmol l(-1); P < 0.001). All patients after high-dose chemotherapy or older than
      50 years had E2 < 0.10 nmol l(-1) and/or amenorrhoea > 1 year and did not develop
      ovarian cysts. Patients still having a menstrual cycle during tamoxifen had a
      high chance (81%) of developing ovarian cysts. Breast cancer patients receiving
      tamoxifen only develop ovarian cysts if their ovaries are able to respond to FSH
      stimulation as shown by E2 production.

PMID- 10206290
TI  - Cytotoxic drugs efficacy correlates with adipose tissue docosahexaenoic acid
      level in locally advanced breast carcinoma.
AB  - Experimental studies indicated that long-chain polyunsaturated fatty acids may
      increase sensitivity of mammary tumours to several cytotoxic drugs. To evaluate
      this hypothesis in breast cancer, we have prospectively studied the association
      between levels of fatty acids stored in breast adipose tissue and the response of
      the tumour to chemotherapy in 56 patients with an initially localized breast
      carcinoma. Adipose breast tissue was obtained at the time of biopsy, and
      individual fatty acids were measured as a percentage of total fatty acids using
      capillary gas chromatography. Patients then received primary chemotherapy,
      combining mitoxantrone, vindesine, cyclophosphamide and 5-fluorouracil every 4
      weeks. Tumour size was reassessed after three cycles of chemotherapy. Tumour
      response was evaluated according to World Health Organization criteria. Complete
      or partial response to chemotherapy was achieved in 26 patients (47%). Level of n
      3 polyunsaturated fatty acids in adipose tissue was higher in the group of
      patients with complete or partial response to chemotherapy than in patients with
      no response or with tumour progression (P < 0.004). Among n-3 polyunsaturated,
      only docosahexaenoic acid (22:6n-3) was significantly associated with tumour
      response (P < 0.005). In a logistic regression analysis taking into account age,
      body mass index and tumour size, 22:6 n-3 level proved to be an independent
      predictor for chemosensitivity (P = 0.03). These results suggest that, in breast
      cancer, 22:6 n-3 may increase the response of the tumour to the cytotoxic agents
      used.

PMID- 10206291
TI  - Diffuse large B-cell non-Hodgkin lymphomas: the clinical relevance of
      histological subclassification.
AB  - In the REAL classification the diffuse large B-cell non-Hodgkin lymphomas (NHL)
      are grouped together, because subclassifications are considered to lack both
      reproducibility and clinical significance. Others, however, claim that patients
      with an immunoblastic NHL have a worse prognosis than patients with other types
      of diffuse large B-cell NHL. Therefore, we investigated the prognostic and
      clinical significance of histological subclassification of diffuse large B-cell
      NHL in a uniformly treated series of patients. For this retrospective study, all
      patients diagnosed as having an immunoblastic (IB) B-cell NHL by the Lymphoma
      Review Panel of the Comprehensive Cancer Center Amsterdam (CCCA) between 1984 and
      1994, and treated according to the guidelines of the CCCA, were analysed.
      Patients with a centroblastic polymorphic subtype (CB-Poly) or centroblastic (CB)
      NHL by the Lymphoma Review Panel who were treated in the Netherlands Cancer
      Institute during the same period according to CCCA guidelines were used as
      reference groups. All patients' records were reviewed. Clinical parameters at
      presentation, kind of therapy and clinical outcome were recorded. All available
      histological slides were separately reviewed by two haemato-pathologists. One
      hundred and seventy-seven patients were included in the study: 36 patients
      (20.3%) with an IB NHL, 69 patients (39%) with a CB-Poly NHL and 72 patients
      (40.7%) with a CB NHL. The patients with an IB NHL tended to be older and
      presented more often with stage I or II and one extranodal site than patients
      with a CB and CB-Poly NHL. None of the subtypes showed a clear preference for
      localization in a particular site. The patients with IB or CB-Poly NHL showed a
      significantly worse prognosis than patients with CB NHL, with a 5-year overall
      survival for patients with CB NHL of 56.3% and for patients with IB or CB-Poly
      NHL 39.1% and 41.6% respectively. The 5-year disease free survival was 53.2% for
      the patients with CB, 32% for the patients with CB-Poly and 26.9% for the
      patients with IB NHL. A multivariate analysis showed that histological subtyping
      was of prognostic significance independent of the International Prognostic Index.
      This finding merits further exploration in prospective studies in order to judge
      the value of subclassification of large B-cell NHL as a guideline in therapy
      choice.

PMID- 10206292
TI  - The IgG1/G2 subclass shift--a sensitive, tissue non-specific marker for
      malignancy. Diagnostic performance with squamous cell carcinoma of the head and
      neck.
AB  - A significant decrease in %IgG1 accompanied by an increase in %IgG2 in total
      serum IgG has been previously reported as a highly sensitive marker for detecting
      early stages of carcinomas of various localizations. Here we investigated the
      question as to whether this phenomenon is also observed in sera of patients with
      squamous cell carcinoma of the head-neck region (SCC-HN), and to evaluate its
      diagnostic performance in the post-operative monitoring. Using quantitative
      affinity chromatography, serum concentrations of IgG1, IgG2 and total IgG were
      determined in 81 patients with different stages of primary and untreated SCC-HN,
      in 51 SCC-HN patients in post-therapeutical follow up, and in 33 patients with
      organ matched benign diseases. The data were compared with a total of 174 healthy
      controls. It was found that (i) 105 SCC-HN patients exhibited a mean value of
      56.0 +/- 0.7% IgG1, which likewise differed from healthy controls (63.2 +/- 0.5)
      and benign diseases (61.5 +/- 1.0) with P < 0.0005, (ii) sensitivities and
      specificities for discriminating primary malignancies from healthy controls were
      70 and 74% respectively, and from benign diseases 65 and 76%, (iii) highest
      sensitivities and specificities were observed with post-therapeutic cases
      suffering from tumour recurrence (88% and 75%) or patients with distant
      metastases (87% and 86%), (iv) apparently tumour-free post-therapeutic patients
      showed a mean %IgG1 not different from the normal value. The decrease in %IgG1
      accompanied by increased %IgG2 is an efficient, sensitive and early marker of SCC
      HN, which appears particularly useful for the post-therapeutic monitoring.

PMID- 10206293
TI  - Audiotapes and letters to patients: the practice and views of oncologists,
      surgeons and general practitioners.
AB  - A range of measures have been proposed to enhance the provision of information to
      cancer patients and randomized controlled trials have demonstrated their impact
      on patient satisfaction and recall. The current study explored the practice and
      views of oncologists, surgeons and general practitioners (GPs) with regards to
      providing patients with consultation audiotapes and summary letters. In stage 1,
      28 semi-structured interviews with doctors were conducted to provide qualitative
      data on which to base a questionnaire. In stage 2, 113 medical oncologists, 43
      radiation oncologists, 55 surgeons and 108 GPs completed questionnaires. Only one
      third of doctors had ever provided patients with a copy of the letter written to
      the oncologist or referring doctor, and one-quarter had provided a summary letter
      or tape. The majority of doctors were opposed to such measures; however, a
      substantial minority were in favour of providing a letter or tape under certain
      conditions. More surgeons and GPs (> two-thirds) were opposed to specialists
      providing a consultation audiotape than oncologists (one-third). Gender, years of
      experience and attitude to patient involvement in decision-making were predictive
      of doctors' attitudes. The majority of doctors remain opposed to offering
      patients personalized information aids. However, practice and perspectives appear
      to be changing.

PMID- 10206294
TI  - Total gastrectomy with simultaneous pancreaticosplenectomy or splenectomy in
      patients with advanced gastric carcinoma.
AB  - A splenectomy or distal pancreaticosplenectomy is often performed simultaneously
      with total gastrectomy in the treatment of gastric carcinoma to facilitate
      dissection of the lymph nodes around the splenic artery and splenic hilus.
      However, the negative impact of splenectomy and pancreaticosplenectomy has also
      been reported. A retrospective analysis was performed to evaluate the outcomes of
      distal pancreaticosplenectomy and total gastrectomy, splenectomy and total
      gastrectomy, and gastrectomy alone in the patients with advanced gastric
      carcinoma without distant metastasis. Prognostic factors were examined. No
      significant differences existed in 5-year survival in the patients who underwent
      gastrectomy with splenectomy, gastrectomy with distal pancreaticosplenectomy, or
      gastrectomy alone. Neither splenectomy, nor distal pancreaticosplenectomy were
      prognostic factors. However, distal pancreaticosplenectomy was an independent
      predictor of pancreatic fistula. In conclusion, the addition of distal
      pancreaticosplenectomy or splenectomy to total gastrectomy for gastric cancer
      increases the risk of severe complications, but does not improve survival.

PMID- 10206295
TI  - A novel immunoscintigraphy technique using metabolizable linker with angiotensin
      II treatment.
AB  - Immunoscintigraphy is a tumour imaging technique that can have specificity, but
      high background radioactivity makes it difficult to obtain tumour imaging soon
      after the injection of radioconjugate. The aim of this study is to see whether
      clear tumour images can be obtained soon after injection of a radiolabelled
      reagent using a new linker with antibody fragments (Fab), in conditions of
      induced hypertension in mice. Fab fragments of a murine monoclonal antibody
      against human osteosarcoma were labelled with radioiodinated 3'-iodohippuryl N
      epsilon-maleoyl-L-lysine (HML) and were injected intravenously to tumour-bearing
      mice. Angiotensin II was administered for 4 h before and for 1 h after the
      injection of radiolabelled Fab. Kidney uptake of 125I-labelled-HML-Fab was much
      lower than that of 125I-labelled-Fab radioiodinated by the chloramine-T method,
      and the radioactivity of tumour was increased approximately two-fold by
      angiotensin II treatment at 3 h after injection, indicating high tumour-to-normal
      tissue ratios. A clear tumour image was obtained with 131I-labelled-HML-Fab at 3
      h post-injection. The use of HML as a radiolabelling reagent, combined with
      angiotensin II treatment, efficiently improved tumour targeting and enabled the
      imaging of tumours. These results suggest the feasibility of PET scan using
      antibody fragment labelled with 18F-fluorine substitute for radioiodine.

PMID- 10206296
TI  - Influence of metastatic site as an additional predictor for response and outcome
      in advanced colorectal carcinoma.
AB  - Every year, 31,230 men and women are diagnosed with colorectal carcinoma, and up
      to 60% of these will ultimately develop advanced disease. However, there is
      little information to identify which patients are most likely to benefit from
      palliative chemotherapy. This analysis is unique in evaluating how the site of
      metastasis influences response and survival. A database of 497 patients treated
      within randomized clinical trials using 5-Fluorouracil (5FU)-based chemotherapy
      at the Royal Marsden Hospital was analysed. The potential for site of metastasis
      as a predictive variable for response to chemotherapy and survival was examined,
      in addition to other clinical parameters. The presence of liver metastases was a
      better predictor for overall response than either performance status or number of
      metastatic sites on presentation. Probability of response was significantly
      decreased by a raised serum carcinoembryonic antigen (CEA) and presence of
      peritoneal metastases. In liver metastases, a normal serum albumin was as
      significant a predictor for response as good performance status. The most
      important predictor for survival was initial performance status. The number of
      metastatic sites on presentation had no influence on survival. Site of metastasis
      can predict for response to 5FU-based chemotherapy and patients should be
      stratified according to the involved site of metastasis in the future.

PMID- 10206297
TI  - Specificity analysis of sera from breast cancer patients vaccinated with MUC1-KLH
      plus QS-21.
AB  - The mucin MUC1 is expressed on breast cancers in an underglycosylated form
      compared to normal tissues and is therefore a potential target for cancer
      immunotherapy. MUC1 contains multiple tandem repeats of the 20 amino acid (aa)
      peptide (VTSAPDTRPAPGSTAPPAHG). The APDTRPA epitope is particularly immunogenic
      since it is recognized by a variety of murine monoclonal antibodies and by some
      sera and cytotoxic T-cells from unimmunized patients with epithelial cancers. We
      have prepared a 30 aa peptide (C)VTSAPDTRPAPGSTAPPAHGVTSAPDTRPA with cysteine at
      the N-terminal end, and used the cysteine for chemical conjugation to keyhole
      limpet haemocyanin (KLH). Six breast cancer patients immunized with this
      conjugate plus the immunological adjuvant QS-21 have all produced high titre (by
      ELISA) IgG and IgM antibodies against the 30 aa MUC1 peptide, but these sera
      reacted moderately, or not at all, with MUC1-positive tumour cells. To understand
      this specificity better, we prepared a series of smaller peptides to determine
      the epitopes recognized by these immune sera in inhibition assays. Only peptides
      containing APDTRPA at the C-terminal end were able to completely inhibit ELISA
      reactivity for the full 30 aa peptide. No sera were completely inhibited by
      APDTR, APDTRP, PDTRPA or any other peptides that did not contain the full APDTRPA
      epitope. Remarkably, sera from all six patients recognized this same epitope and
      were completely inhibited by only this epitope. The specificity of these sera (1)
      primarily for C-terminal APDTRPA, and the absence of this epitope at the C
      terminal end of any tumour mucins, and (2) the N-terminal APDTRPA alanine, which
      is normally buried in the beta turn MUC1 assumes in its secondary structure may
      explain the moderate to weak reactivity of these high titer sera against MUC1
      positive tumour cells.

PMID- 10206299
TI  - The prognostic significance of allelic imbalance at key chromosomal loci in oral
      cancer.
AB  - Forty-eight primary oral squamous cell carcinomas (SCC) were screened for allelic
      imbalance (AI) at 3p24-26, 3p21, 3p13, 8p21-23, 9p21, 9q22 and within the Rb, p53
      and DCC tumour suppressor genes. AI was detected at all TNM stages with stage 4
      tumours showing significantly more aberrations than stage 1-3. A factional
      allelic loss (FAL) score was calculated for all tumours and a high score was
      associated with development of local recurrence (P = 0.033) and reduced survival
      (P = 0.0006). AI at one or more loci within the 3p24-26, 3p21, 3p13 and 9p21
      regions or within the THRB and DCC genes was associated with reduced survival.
      The hazard ratios for survival analysis revealed that patients with AI at 3p24
      26, 3p13 and 9p21 have an approximately 25 times increase in their mortality rate
      relative to a patient retaining heterozygosity at these loci. AI at specific
      pairs of loci, D3S686 and D9S171 and involving at least two of D3S1296, DCC and
      D9S43, was a better predictor of prognosis than the FAL score or TNM stage. These
      data suggest that it will be possible to develop a molecular staging system which
      will be a better predict of outcome than conventional clinicopathological
      features as the molecular events represent fundamental biological characteristics
      of each tumour.

PMID- 10206298
TI  - Detection of cytokeratins 19/20 and guanylyl cyclase C in peripheral blood of
      colorectal cancer patients.
AB  - The clinical significance of detecting supposed tumour cell-derived mRNA
      transcripts in blood using the polymerase chain reaction (PCR) remains unclear.
      We have used a fully quantitative 5'-nuclease RT-PCR assay to screen for the
      expression of cytokeratins (ck) 19 and 20 and guanylyl cyclase C (GCC) in the
      peripheral blood of 21 healthy controls and 27 colorectal cancer patients.
      Expression of cytokeratin 19 and 20 mRNA was detected in 30% and 100% of samples,
      respectively, taken from healthy volunteers. There was no apparent difference in
      ck19 and ck20 mRNA transcription levels between controls and patients, or between
      patients with different Dukes' stages. While GCC mRNA was detected in only 1/21
      control samples, it was expressed in approximately 80% of patients, although
      again there was no correlation between GCC levels and disease stage.
      Transcription levels of all three markers varied considerably between samples,
      even between samples taken from the same person at different times. We conclude
      that neither ck19 nor ck20 are reliable markers for the detection of colon
      epithelial cells in peripheral blood and that an evaluation of the usefulness of
      GCC awaits further longitudinal studies.

PMID- 10206300
TI  - Gelatinase-A (MMP-2), gelatinase-B (MMP-9) and membrane type matrix
      metalloproteinase-1 (MT1-MMP) are involved in different aspects of the
      pathophysiology of malignant gliomas.
AB  - Matrix metalloproteinases (MMPs) have been implicated as important factors in
      gliomas since they may both facilitate invasion into the surrounding brain and
      participate in neovascularization. We have tested the hypothesis that deregulated
      expression of gelatinase-A or B, or an activator of gelatinase-A, MT1-MMP, may
      contribute directly to human gliomas by quantifying the expression of these MMPs
      in 46 brain tumour specimens and seven control tissues. Quantitative RT-PCR and
      gelatin zymography showed that gelatinase-A in glioma specimens was higher than
      in normal tissue; these were significantly elevated in low grade gliomas and
      remained elevated in GBMs. Gelatinase-B transcript and activity levels were also
      higher than in normal brain and more strongly correlated with tumour grade. We
      did not see a close relationship between the levels of expression of MT1-MMP mRNA
      and amounts of activated gelatinase-A. In situ hybridization localized gelatinase
      A and MT1-MMP transcripts to normal neuronal and glia, malignant glioma cells and
      blood vessels. In contrast, gelatinase-B showed a more restricted pattern of
      expression; it was strongly expressed in blood vessels at proliferating margins,
      as well as tumour cells in some cases. These data suggest that gelatinase-A, -B
      and MT1-MMP are important in the pathophysiology of human gliomas. The primary
      role of gelatinase-B may lie in remodelling associated with neovascularization,
      whereas gelatinase-A and MT1-MMP may be involved in both glial invasion and
      angiogenesis.

PMID- 10206301
TI  - Cytochrome P450 CYP3A in human renal cell cancer.
AB  - Renal cell cancer is the main malignant tumour of the kidney and has an
      increasing incidence. This type of tumour has a poor prognosis and shows
      intrinsic resistance to several anti-cancer drugs. The CYP3A P450 family, which
      consists of three closely related forms, is involved in the oxidative activation
      and deactivation of a variety of carcinogens and several anti-cancer drugs. In
      this study the presence and cellular localization of CYP3A has been investigated
      using a combination of immunohistochemistry, immunoblotting and reverse
      transcriptase polymerase chain reaction (RT-PCR) in renal cell cancer and
      corresponding normal kidney. CYP3A was consistently expressed in both renal call
      cancer and in normal kidney. In renal cell cancer, CYP3A was localized to tumour
      cells and in normal kidney the predominant cellular localization of CYP3A was to
      proximal tubular epithelial cells. RT-PCR showed that both CYP3A5 mRNA and CYP3A7
      mRNA were consistently present in both tumour and normal samples, while CYP3A4
      mRNA was present in 65% of tumours and 90% of normal samples. This study
      indicates that individual members of the CYP3A family are expressed in renal cell
      cancer. The presence of CYP3A in renal cell cancer might be important in the
      metabolic potentiation as well as the detoxification of chemotherapeutic agents
      used to renal cancer.

PMID- 10206302
TI  - Comparative genomic hybridization detects many recurrent imbalances in central
      nervous system primitive neuroectodermal tumours in children.
AB  - A series of 23 children with primitive neuroectodermal tumours (PNET) were
      analysed with comparative genomic hybridization (CGH). Multiple chromosomal
      imbalances have been detected in 20 patients. The most frequently involved
      chromosome was chromosome 17, with a gain of 17q (11 cases) and loss of 17p
      (eight cases). Further recurrent copy number changes were detected. Extra copies
      of chromosome 7 were present in nine patients and gains of 1q were detected in
      six patients. A moderate genomic amplification was detected in one patient,
      involving two sites on 3p and the whole 12p. Losses were more frequent, and
      especially involved the chromosomes 11 (nine cases), 10q (eight cases), 8 (six
      cases), X (six patients) and 3 (five cases), and part of chromosome 9 (five
      cases). These recurrent chromosomal changes may highlight locations of novel
      genes with an important role in the development and/or progression of PNET.

PMID- 10206304
TI  - Restriction fragment length polymorphism of the L-myc gene is not a prognostic
      factor in bladder cancer patients.
AB  - The L-myc restriction fragment length polymorphism has been suggested to be of
      prognostic significance in some types of primary tumours. We examined the
      prognostic and susceptibility significance of the L-myc genotype in a group of 98
      bladder cancer patients. The L-myc genotype did not correlate with any pathologic
      parameter and does not offer any clinical utility in patients with bladder
      cancer.

PMID- 10206303
TI  - Expression of the thymidine phosphorylase gene in epithelial ovarian cancer.
AB  - Thymidine phosphorylase (TP) is associated with angiogenesis and the progression
      of solid tumours. High intracellular levels of this enzyme indicate increased
      chemosensitivity to pyrimidine antimetabolites. TP gene expression in 56 cases of
      epithelial ovarian cancer (27 of serous, 10 mucinous, 12 endometrioid, five clear
      cell and two undifferentiated) were analysed by polymerase chain reaction of RNA
      after reverse transcription. These included eight of low malignant potential.
      Twenty were stage I, four stage II, 27 stage III and five stage IV. The level of
      TP gene expression was presented by the relative yield of the TP gene to the
      beta2-microglobulin gene. TP gene expression ranged from 0.19 to 5.38 (median
      0.93). The value of TP gene expression in stage III-IV was significantly higher
      than that of TP gene expression in stage I-II (P = 0.0005). Histological grade
      significantly associated with TP gene expression (P = 0.008), but histological
      subtype did not (P = 0.166). A follow-up study of 34 cases after complete
      resection of the primary tumours by surgical operation was performed. TP gene
      expression of the cases with recurrence showed significantly higher levels
      compared to cases without recurrence (P = 0.049). Survival data were available
      for 47 of the 56 patients. The prognosis of the patients with high TP gene
      expression (equal to, or greater than, median) was to be significantly worse than
      patients with low TP gene expression (less than median) (P = 0.021). The TP gene
      expression level may play one of the key roles in the biology of ovarian
      epithelial cancer and define a more aggressive tumour phenotype. A new
      therapeutic intervention mediated by TP protein activity is anticipated.

PMID- 10206305
TI  - Reduced bone mineral density in young adults following cure of acute
      lymphoblastic leukaemia in childhood.
AB  - Bone mineral density (BMD), serum osteocalcin and type I collagen C-telopeptide
      (ICTP) were assessed in a cohort of 31 (16 males) adults who had received cranial
      irradiation in childhood as part of their treatment for acute lymphoblastic
      leukaemia (ALL). Markers of bone turnover were compared with those of 35 age and
      body mass index (BMI) matched young adults (18 male). Growth hormone status had
      previously been determined using an insulin tolerance test and arginine
      stimulation test. Eight patients were classified as severe growth hormone
      deficiency (group 1), 12 patients as growth hormone insufficient (group 2) and 11
      patients as normal (group 3). Vertebral trabecular BMD, lumbar spine and femoral
      neck integral BMD and forearm cortical bone mineral content (BMC) was measured
      17.8 (6.8-28.6) years after cranial irradiation and was expressed as Z (standard
      deviation) scores. There was a significant reduction in vertebral trabecular BMD
      (median Z score -1.25, P < 0.001), in lumbar spine integral BMD (median Z score 
      0.74, P = 0.001), in forearm cortical BMC (median Z score -1.35, P < 0.001), and
      less so in femoral neck integral BMD (median Z score -0.43, P = 0.03). There was
      no difference among the growth hormone status groups for the following BMD
      measurements: vertebral trabecular BMD, lumbar spine integral BMD or femoral neck
      integral BMD (P = 0.8, P = 0.96 and P = 0.4 respectively). There was only a
      marginal significant difference for BMD at the wrist between growth hormone
      status groups (P = 0.04). There was no correlation between the BMD measurements
      with time since or age at diagnosis and no difference in markers of bone turnover
      between patients and controls; median serum osteocalcin 13.3 and 12.0 ng ml (P =
      0.7), respectively, and for ICTP 5.0 and 4.9 microg L (P = 0.67) respectively. In
      conclusion, there is a highly significant reduction in BMD in young adults
      following treatment for ALL in childhood. The reduction in BMD affects both
      trabecular and cortical bone but did not seem to be related to time since
      diagnosis, age at diagnosis, or current growth hormone status. Possible
      explanations include a direct effect of chemotherapy, steroids or both on bone
      during childhood and hence an effect on the accretion of bone mass. In view of
      the risk of fractures in patients with osteopenia, adults treated for ALL in
      childhood may be at an increased risk of bone fractures later in life
      irrespective of the underlying cause of the osteopenia and thus intervention
      should be considered.

PMID- 10206306
TI  - A multifactorial approach including tumoural epidermal growth factor receptor,
      p53, thymidylate synthase and dihydropyrimidine dehydrogenase to predict
      treatment outcome in head and neck cancer patients receiving 5-fluorouracil.
AB  - The prognostic value of tumoural epidermal growth factor receptor (EGFR), p53,
      thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) was analysed
      on 82 advanced head and neck cancer patients (71 men, 11 women; mean age 59).
      Induction treatment was cisplatin-5-FU +/- folinic acid (61 patients, Chem group)
      or concomitant cisplatin-5-FU-radiotherapy (21 patients, RChem group). EGFR
      (binding assay), p53 protein (Sangtec immunoluminometric assay), TS and DPD
      activities (radioenzymatic assays) were measured on biopsies obtained at time of
      diagnosis. Significant positive correlation was demonstrated between p53 and
      EGFR. In the RChem group, p53 was higher in non-complete responders (median 1.03
      ng mg(-1)) than in complete responders (median 0.08 ng mg(-1)) (P = 0.057).
      Univariate Cox analyses stratified on treatment group showed that specific
      survival (33 events) was significantly related to T staging, p53 taken as
      continuous or categorial (below vs over 0.80 ng mg(-1)) variable, and EGFR (below
      vs over 220 fmol mg(-1)); survival increased when EGFR and p53 were below
      thresholds. Multivariate stepwise analysis including T staging, EGFR and p53
      revealed that T staging and EGFR were independent predictors of survival;
      relative risks were 3.68 for T staging and 2.65 for EGFR. Overall, EGFR remained
      an independent prognostic factor when response to treatment and T staging were
      considered in the multivariate analysis.

PMID- 10206307
TI  - p21/WAF1 expression as related to p53, cell proliferation and prognosis in
      epithelial ovarian cancer.
AB  - The role and prognostic value of the tumour suppressor p21/WAF1 expression in
      epithelial ovarian cancer has not yet been defined. Therefore, the expression of
      p21/WAF1 was assessed immunohistochemically (IHC) in 316 epithelial ovarian
      malignancies in relation to p53, cell proliferation and patient survival.
      p21/WAF1 expression was inversely correlated with p53 and cell proliferation. Low
      p21/WAF1 expression was significantly associated with high grade of the tumour (P
      = 0.0005), advanced FIGO stage (P = 0.001) and primary residual tumour (P =
      0.0001). Low p21/WAF1 expression was a marker of poor overall survival (P =
      0.012). Similarly, p53-positivity and high cell proliferative activity were
      significant predictors of poor survival in univariate analyses. Moreover, the
      patients with p21-/p53+ tumours had a poorer overall (P < 0.00005) and recurrence
      free (P = 0.0005) survival in univariate analyses, and the p21/p53 expression
      independently predicted tumour recurrence in Cox's multivariate analysis. Our
      results suggest that p21/WAF1 expression is mostly p53-dependent in epithelial
      ovarian cancer. High p21/WAF1 expression seems to function as a negative cell
      cycle regulator and as a marker of favourable disease outcome in epithelial
      ovarian cancer. In addition, the patients with their tumour expressing no or low
      p21/WAF1 protein but positive for p53 had a notably higher risk of recurrent
      disease, implicating that these patients might be more prone to treatment
      failures.

PMID- 10206308
TI  - E-cadherin and alpha-, beta- and gamma-catenin expression in prostate cancers:
      correlation with tumour invasion.
AB  - The E-cadherin-catenin complex plays an important role in establishing and
      maintaining intercellular connections and morphogenesis and reduced expression of
      its constituent molecules is associated with invasion and metastasis. In the
      present study, we examined E-cadherin and alpha-, beta- and gamma-catenin levels
      in tumour tissues obtained by radical prostatectomy in order to investigate the
      relationship with histopathological tumour invasion. Immunohistochemical findings
      for 45 prostate cancer specimens demonstrated aberrant expression of each
      molecule to be associated with dedifferentiation and, in addition, alteration of
      staining patterns for the three types of catenin was significantly correlated
      with capsular but not lymphatic or vascular invasion. The data thus suggest that
      three types of catenin may be useful predictive markers for biological
      aggressiveness of prostate cancer.

PMID- 10206309
TI  - Second malignant neoplasms after a first cancer in childhood: temporal pattern of
      risk according to type of treatment.
AB  - The variation in the risk of solid second malignant neoplasms (SMN) with time
      since first cancer during childhood has been previously reported. However, no
      study has been performed that controls for the distribution of radiation dose and
      the aggressiveness of past chemotherapy, which could be responsible for the
      observed temporal variation of the risk. The purpose of this study was to
      investigate the influence of the treatment on the long-term pattern of the
      incidence of solid SMN after a first cancer in childhood. We studied a cohort of
      4400 patients from eight centres in France and the UK. Patients had to be alive 3
      years or more after a first cancer treated before the age of 17 years and before
      the end of 1985. For each patient in the cohort, the complete clinical,
      chemotherapy and radiotherapy history was recorded. For each patient who had
      received external radiotherapy, the dose of radiation received by 151 sites of
      the body were estimated. After a mean follow-up of 15 years, 113 children
      developed a solid SMN, compared to 12.3 expected from general population rates. A
      similar distribution pattern was observed among the 1045 patients treated with
      radiotherapy alone and the 2064 patients treated with radiotherapy plus
      chemotherapy; the relative risk, but not the excess absolute risk, of solid SMN
      decreased with time after first treatment; the excess absolute risk increased
      during a period of at least 30 years after the first cancer. This pattern
      remained after controlling for chemotherapy and for the average dose of radiation
      to the major sites of SMN. It also remained when excluding patients with a first
      cancer type or an associated syndrome known to predispose to SMN. When compared
      with radiotherapy alone, the addition of chemotherapy increases the risk of solid
      SMN after a first cancer in childhood, but does not significantly modify the
      variation of this risk during the time after the first cancer.

PMID- 10206310
TI  - Evaluation of screening for nasopharyngeal carcinoma: trial design using Markov
      chain models.
AB  - In this paper, we develop a Markov chain model to estimate parameters pertaining
      to the natural history of nasopharyngeal carcinoma (NPC). The model is of
      progression from no disease to Epstein-Barr virus (EBV) infection, preclinical
      screen-detectable tumour and clinical tumour. We derive tentative estimates of
      the parameters of the model, based on limited published data, to assess the
      efficacy of serum screening in conjunction with clinical assessment (indirect
      mirror examination for NPC), for example the average duration of the preclinical
      screen-detectable phase is estimated as 3.1 years. We further apply these
      parameters to a hypothetical screening trial in the Hong Kong population to
      assess the efficacy of serum screening with clinical assessment by different
      combinations of screening regime. Results suggest: (1) there is no substantial
      difference between 3-yearly and 6-yearly serum screening; and (2) within the same
      serum screening regime annual and 3-yearly clinical assessment can prevent 33%
      and 28% of deaths from NPC respectively. Prediction of deaths and surrogate end
      points can be used to estimate the required sample size and duration for
      designing a randomized trial of screening for NPC. Based on these findings and
      power projections, we suggest a design for a randomized trial in a high incidence
      area such as Hong Kong.

PMID- 10206312
TI  - Diet, body size and menarche in a multiethnic cohort.
AB  - A multiethnic cohort of 1378 Southern California school girls aged 8-13 years was
      followed for 4 years to evaluate factors predicting age at menarche, a risk
      factor for breast cancer. Height and weight were measured and dietary intake was
      assessed using a semi-quantitative food frequency questionnaire. Of 939 girls
      providing data on menarcheal status, 767 were premenarcheal at the start of the
      study; 679 girls provided acceptable dietary data and were included in the
      analyses. Cox proportional hazards models were used to assess the relationship
      between diet, body size, ethnicity and age at menarche. Hispanic, Asian/Pacific
      Island and African-American girls were more likely to experience early menarche
      than non-Hispanic white girls. Tall (> 148.6 cm) versus short (< 135.9 cm) girls
      experienced earlier menarche (relative hazard (RH) = 2.9, 95% confidence interval
      (CI) 2.1-4.1) as did those with high Quetelet's index (QI, kg m(-2)) (> 20.7)
      versus low QI (< 16.1) (RH = 2.2, 95% CI 1.7-2.9). Of all the dietary variables
      analysed, only energy intake was related to age at menarche. High versus low
      energy intake (> 12,013 kJ vs < 7004 kJ) was associated with a delay in menarche
      (RH = 0.7, 95% CI 0.5-0.9); this finding was limited to a subset of heavy
      Hispanic girls who appeared to underreport their dietary intake.

PMID- 10206311
TI  - Reproductive factors related to the risk of colorectal cancer by subsite: a case
      control analysis.
AB  - The authors hypothesized that reproductive factors of colorectal cancer, which
      are probably mediated by endogenous hormones, would differ according to colonic
      subsite. Information on reproductive factors was obtained from 372 female
      colorectal cancer cases (113 proximal colon, 126 distal colon, 133 rectum) and
      31,061 cancer-free controls at the Aichi Cancer Center Hospital, Japan, between
      1988 and 1995. Multiple logistic analysis showed that late age at interview,
      family history of colorectal cancer among first-degree relatives, menstrual
      regularity, late age at menopause, late age at first pregnancy and late age at
      first full-term pregnancy were significantly associated with the risk of
      colorectal cancer. None of the risk factors were significantly dissociated
      between colon and rectal cancer. In polytomous logistic regression analysis,
      particularly noteworthy was the fact that the odds ratios for age at menarche (P
      value for heterogeneity of odds ratios = 0.010), age at first pregnancy (P =
      0.016) and age at first full-term pregnancy (P = 0.028) were significantly higher
      for distal than for proximal colon cancer. This study supports the hypotheses
      that there might be an association between reproductive factors and risk of colon
      cancer, and that the carcinogenesis of colon cancer, by subsite, might show
      aetiologic distinctions.

PMID- 10206313
TI  - Physical activity and risk of cancers of the colon and rectum: an Italian case
      control study.
AB  - We investigated the relationships between risk of colon and rectal cancers and
      physical activity in both sexes at different ages by a case-control study
      conducted between 1991 and 1996 in six Italian centres. Cases were 1225 patients
      (688 men, 537 women) below the age of 75 with colon cancer and the controls
      included 4154 patients (2073 men, 2081 women) admitted to hospital for acute, non
      neoplastic conditions. We also analysed 722 cases of rectal cancer. Compared with
      the lowest level of occupational physical activity at 30-39 years old the odds
      ratios (OR) for the highest level were 0.64 (95% confidence interval, CI 0.44
      0.93) in men and 0.49 (95% CI 0.33-0.72) in women. The inverse association in
      both sexes was similar at 15-19 and 50-59 years old. No association was found in
      either sex for leisure-time physical activity. For both sexes the inverse
      relationship between occupational physical activity at 30-39 years old and colon
      cancer risk was not significantly heterogeneous across strata of selected
      covariates, and for ascending, transverse, descending and sigmoid colon. Rectal
      cancer risk was not associated with any measure of physical activity (OR = 1.32
      for men and 0.88 for women for the highest level of occupational physical
      activity at 30-39 years old compared with the lowest). This study confirms that
      occupational physical activity is protective against colon, but not against
      rectal cancer.

PMID- 10206314
TI  - Serum folate, homocysteine and colorectal cancer risk in women: a nested case
      control study.
AB  - Accumulating evidence suggests that folate, which is plentiful in vegetables and
      fruits, may be protective against colorectal cancer. The authors have studied the
      relationship of baseline levels of serum folate and homocysteine to the
      subsequent risk of colorectal cancer in a nested case-control study including 105
      cases and 523 matched controls from the New York University Women's Health Study
      cohort. In univariate analyses, the cases had lower serum folate and higher serum
      homocysteine levels than controls. The difference was more significant for folate
      (P < 0.001) than for homocysteine (P = 0.04). After adjusting for potential
      confounders, the risk of colorectal cancer in the subjects in the highest
      quartile of serum folate was half that of those in the lowest quartile (odds
      ratio, OR = 0.52, 95% confidence interval, CI = 0.27-0.97, P-value for trend =
      0.04). The OR for the highest quartile of homocysteine, relative to the lowest
      quartile, was 1.72 (95% CI = 0.83-3.65, P-value for trend = 0.09). In addition,
      the risk of colorectal cancer was almost twice as high in subjects with below
      median serum folate and above-median total alcohol intake compared with those
      with above-median serum folate and below-median alcohol consumption (OR = 1.99,
      95% CI = 0.92-4.29). The potentially protective effects of folate need to be
      confirmed in clinical trials.

PMID- 10206315
TI  - Risk factors for breast cancer in nulliparous women.
AB  - The relation between hormonal and lifestyle factors and breast cancer risk in
      nulliparae was investigated using data from two case-control studies conducted in
      Italy between 1983 and 1994. The study included 1041 nulliparae with
      histologically confirmed incident breast cancer and 1002 nulliparous controls
      admitted to hospital for a wide range of acute, non-neoplastic, nonhormone
      related diseases. In premenopausal nulliparae, there was an inverse relation with
      age at menarche [odds ratios (OR) 0.45; 95% confidence intervals (CI) 0.24-0.86
      for > or = 15 years vs < 12], while no association emerged in postmenopausal.
      Breast cancer risk increased with age at menopause, the OR being 1.91 (95% CI
      1.26-2.90) for nulliparae reporting age at menopause > or = 53 years compared
      with < 45. Abortion was not related to breast cancer risk, the OR being 0.92 for
      any spontaneous, 0.97 for any induced and 0.77 for > or = 2 total abortions
      compared to none. The OR was 1.75 (95% CI 1.03-2.97) for women reporting their
      first abortion at age > or = 30 years compared with < 30. Oral contraceptives and
      hormone replacement therapy in menopause were moderately related to risk. The OR
      was 2.71 (95% CI 1.85-3.95) in nulliparae with a family history of breast cancer
      and 1.60 (95% CI 1.20-2.14) in those with a history of benign breast disease.
      Compared with nulliparae reporting a low physical activity, the OR was 0.79 (95%
      CI 0.54-1.16) for those reporting intermediate/high activity. Breast cancer risk
      increased with total energy intake, the OR being 1.65 (95% CI 0.99-2.75) in the
      highest tertile; beta-carotene was inversely related to risk (OR 0.60, 95% CI
      0.38-0.95) for the highest tertile. Thus, most risk factors for breast cancer in
      nulliparae were similar to those in women generally.

PMID- 10206316
TI  - Descriptive epidemiology of gastrointestinal non-Hodgkin's lymphoma in a
      population-based registry.
AB  - The incidence of non-Hodgkin's lymphoma (NHL), particularly at certain extranodal
      sites, has been demonstrated to be rising, at least in the USA, more than for any
      other malignancy. One of the major sites of extranodal NHL is the
      gastrointestinal tract, though little is known of its epidemiological
      characteristics. Over an 8-year period (1986 to 1993) 1069 primary
      gastrointestinal NHL cases were reported to the Leukaemia Research Fund Data
      Collection Survey which covers many parts of England and Wales. Age-standardized
      incidence rates of gastrointestinal NHL at all sites (0.58/10(5) per year),
      gastric (0.24/10(5) per year), small bowel (0.17/10(5) per year) and large bowel
      (0.06/1(5) per year) confirmed that the UK has the lowest rates of
      gastrointestinal NHL in Europe. An excess of males was observed at all ages and
      for all sites. Time-trend analyses showed annual increases in incidence rates for
      gastric (6.3%) and small bowel (5.9%) NHL although a concomitant decrease in
      gastrointestinal NHL of unknown site suggested that at least part of these
      increases had resulted from more accurate diagnoses. Overall, the incidence of
      gastrointestinal NHL significantly increased by 2.7% per annum and was limited to
      the population aged over 50 years in this series.

PMID- 10206319
TI  - Anthracycline dose and liver dysfunction.

PMID- 10206318
TI  - Epidemiology of Kaposi's sarcoma in Scotland, 1976-1996.
AB  - Based on data from the Scottish Cancer Registry, the epidemiology of Kaposi's
      sarcoma (KS) in Scotland during the period 1976-96 is described. In males, the
      annual age-standardized incidence rate (World standard population) increased from
      less than 0.09 per 100,000 before 1986 to 0.44 in 1991 and then decreased to
      around 0.17. Peak incidence is now at ages 30-39 compared with ages 80+ during
      the period 1976-82; and by 1986-96 the standardized incidence ratio for the
      Health Board which includes Edinburgh had risen to almost four times the national
      level. These changes are largely consistent with the pattern of HIV infection in
      Scotland. However, in both sexes, relative to other neoplasms, and in
      international terms, KS remains rare in Scotland. For patients diagnosed during
      1976-92, cumulative observed survival at 5 years was 8.7% at ages 0-49 compared
      with 49.8% at ages 50-84, reflecting the more aggressive course of AIDS-related
      KS, as well as the co-morbidity and competing causes of death associated with
      AIDS.

PMID- 10206317
TI  - Low frequency of germline E-cadherin mutations in familial and nonfamilial
      gastric cancer.
AB  - Little is known about the relative contributions of genetic and environmental
      factors to the development of gastric cancer. Mutations in the cell adhesion
      molecule E-cadherin are recognized to be associated with the development of
      undifferentiated, diffuse and invasive gastric cancers. A recent study of two
      gastric cancer families has shown that germline mutations in the E-cadherin gene
      can be causative (Guilford P et al, Nature 1998; 26: 402-405). We have examined
      the E-cadherin gene for constitutive mutations in a systematic series of 106
      gastric cancer patients, 10 with a family history of the disease and 96 sporadic
      cases. No pathogenic mutations were observed in any of the 106 patients. The
      results indicate that germline mutations in E-cadherin will not account for more
      than 3% of gastric cancers.

PMID- 10206320
TI  - Azimilide pharmacokinetics and pharmacodynamics upon multiple oral dosing.
AB  - This study assessed steady-state azimilide pharmacokinetics and pharmacodynamics
      in 119 healthy male and female volunteers. Parallel groups of 18-40-year-old
      subjects received doses of 35, 100, 150 or 200 mg day(-1) for up to 14 days, with
      1, 2 or 3 days of loading. Another group of > 55-year-old subjects received 100
      mg day(-1) with a 3-day loading regimen. There was a slight overshoot of steady
      state (24%) after loading, but concentrations decreased to steady-state by day 7.
      Mean peak steady-state azimilide concentrations ranged from 186 to 1030 ng mL(-1)
      across the 35-200 mg day(-1) dose range, while mean trough steady-state azimilide
      concentrations ranged from 108 to 549 ng mL(-1). Azimilide pharmacokinetics were
      proportional to dose, except for renal clearance, and did not differ between 18
      40-year-old and > 55-year-old subjects. Pharmacodynamics did not differ across
      dose groups. The mean maximum effect (Emax) ranged from 24 to 28% change in QTc
      from baseline. The concentration needed to attain one half Emax ranged from 432
      to 542 ng mL(-1) across dose groups. Equilibration was rapid between blood and
      the biophase, with equilibration half-lives of less than 1 min.

PMID- 10206321
TI  - Absorption and disposition of a tripeptoid and a tetrapeptide in the rat.
AB  - The present study is concerned with the absorption and disposition of a
      tripeptoid (N-substituted glycine derivative) and a tetrapeptide in the rat. The
      two compounds have similar backbone structures but differ with respect to the
      presence or absence of peptide bond. [3H]tripeptoid and [3H]tetrapeptide were
      administered orally (30 mg kg(-1)) and intravenously (i.v.) (30 or 3 mg kg(-1))
      to Sprague Dawley rats. Blood, urine and feces were collected at designated times
      for radioactivity and parent drug analysis. The intestinal absorptive clearances
      of the tripeptoid and tetrapeptide were studied using an in situ rat intestinal
      perfusion model. The octanol/water partition coefficient of these two compounds
      was also determined. The results showed that the peptoid and peptide have similar
      absorptive clearance and octanol/water partitioning, but different in vivo
      absorption and disposition characteristics. The absorptive clearances of the
      tripeptoid and tetrapeptide were 6.7 and 4.8 x 10(-4) mL min(-1) cm(-1),
      respectively, and the corresponding octanol/water partition coefficients were
      0.39 and 0.30. The extent of oral absorption of the tripeptoid was only 3-8%,
      consistent with its low absorptive clearance. In contrast, the apparent
      absorption of the tetrapeptide was > 75% of the radioactive dose. The peptide was
      completely metabolized within 2 h after an i.v. dose, whereas the peptoid was
      stable in blood and was primarily eliminated in feces as intact drug. In
      conclusion, the difference in in vivo absorption and disposition between the
      peptoid and peptide was apparently due to the presence or absence of a peptide
      bond. The tetrapeptide was subject to rapid metabolism in the body. Its
      relatively high absorption appeared to represent the absorption of metabolized
      radioactive fragments. The peptoid appears to have advantages over the peptide in
      term of metabolic stability, but its low oral absorption and rapid biliary
      excretion present additional challenges in the selection of an optimal drug
      candidate.

PMID- 10206322
TI  - Mechanism of the uricosuric action of the anti-inflammatory drug E3040 used to
      treat inflammatory bowel disease I: study using a rat model of hyperuricemia.
AB  - E3040, a new class of anti-inflammatory drug, was found to reduce the plasma uric
      acid level in the first phase of clinical studies. In the present study, the
      mechanism of the uricosuric action of E3040 was investigated using the
      hyperuricemia model rat. The fractional excretion of uric acid (FEurate), an
      indicator of the excretion of uric acid in the renal tubules, at 30, 60 and 90
      min after administration of E3040 (50 mg kg(-1)) was significantly elevated as
      compared with that in the control. This elevation of the FEurate by E3040 was
      dose-dependent. Although the FEurate was elevated spontaneously 30 min after
      administration of E3040-sulfate (E-Sul) and glucuronide (E-Glu) (100 mg kg(-1),
      respectively), the value was not significantly different from the control. Based
      on these results, it was suggested that E3040 has a uricosuric action, probably
      in the proximal tubules, and the uricosuric action after administration of E3040
      may be mainly due to the parent drug. Concerning the tissue distribution, the
      kidney concentration of E-Sul after i.v. administration of the E3040 (50 mg kg(
      1)) was higher than that of the parent drug (kidney/plasma ratio approximately
      2).

PMID- 10206324
TI  - Serum protein binding of tolterodine and its major metabolites in humans and
      several animal species.
AB  - The aim of this study was to determine in vitro protein binding of tolterodine
      and its 5-hydroxymethyl (5-HM) and N-dealkylated metabolites in serum from humans
      and several animal species at concentrations similar to those obtained in
      clinical and preclinical studies. Binding of tolterodine and the two metabolites
      to human serum albumin and alpha1-acid glycoprotein (AAG) was also assessed, as
      was binding of tolterodine to red blood cells. Ex vivo protein binding of
      tolterodine and 5-HM was determined in serum samples from healthy volunteers
      treated with oral tolterodine 4 mg twice daily for 8 days. Tolterodine exhibited
      high protein binding in human serum; the unbound fraction (f(u)) was 3.7%. The
      unbound fraction of tolterodine in cat and dog serum (1.5 and 2.1%, respectively)
      was lower compared with human serum; f(u) was higher in the other species
      investigated (rat, 22%; mouse, 16-17%; rabbit, 39%). The unbound fraction of 5-HM
      was much higher in serum from humans (36%) and all animal species investigated
      (mouse, 72%; rabbit, 68%; cat, 32%; dog, 45%). Binding of N-dealkylated
      tolterodine to proteins in human serum was intermediate (f(u) 14%). AAG was the
      major binding protein for tolterodine and 5-HM, and the degree of binding
      increased with increasing concentration of the protein. The association constant
      of 5-HM for AAG was lower than that of tolterodine (1.3 x 10(5) M(-1) versus 2.1
      x 10(6) M(-1)). The blood:plasma tolterodine concentration ratio was 0.6 in both
      humans and dog; thus, a minor fraction of tolterodine was present in red blood
      cells compared with plasma (0.18 and 0.36, respectively). In the mouse,
      tolterodine was equally present in blood and plasma. In ex vivo samples, f(u)
      values for tolterodine (pH adjusted) varied between 1.6 and 4.9% (mean 2.8%),
      which could be explained by differences in AAG concentrations. There was good
      correlation between observed f(u) values for tolterodine and those predicted on
      the basis of AAG levels. Similar findings were observed for 5-HM.

PMID- 10206323
TI  - Contribution of P-glycoprotein to bunitrolol efflux across blood-brain barrier.
AB  - In this study, we investigated the mechanism of the blood-brain barrier (BBB)
      transport of bunitrolol (BTL), as a model of beta-blocker, in vivo and in vitro.
      In order to define the contribution of P-glycoprotein (P-gp) to the active efflux
      of BTL from brain to blood, we examined the in vivo brain distribution of BTL in
      mdr1a(-/-) mice with a disrupted mdr1a gene. After intravenous administration of
      BTL to mdr1a(-/-) mice, the brain concentration and Kp value of BTL were
      significantly increased as compared with those in mdr1a(+/+) mice. Next, the
      contribution of the mdr1a P-gp to in vitro uptake of BTL was compared in LV500
      cells and L cells (mouse mdr1a-expressing cells and host cells, respectively).
      The intracellular accumulations of [3H]vinblastine and BTL by LV500 cells were
      lower than those by L cells, but were significantly increased by verapamil, a P
      gp inhibitor. Furthermore, the BTL uptake by KB-VJ300 cells, which express human
      P-gp, was also significantly lower than that by KB host cells, and was increased
      by verapamil. The steady-state uptake of BTL by LLC-GA5-COL300 cells, expressing
      human P-gp, was significantly increased in the presence of 20 microM cyclosporin
      A (another P-gp inhibitor), which had no effect in the LLC-PK1 host cells. On the
      other hand, the steady-state intracellular accumulation of BTL by MBEC4 cells,
      which express mdr1b P-gp instead of mdr1a P-gp, was not significantly changed in
      the presence of verapamil. This finding suggested that BTL is not a good
      substrate for mdr1b P-gp. In conclusion, our results suggest that BTL is
      transported from brain to blood by mdr1a P-gp in mice and by MDR1 in humans, and
      this presumably accounts for the low brain distribution of BTL.

PMID- 10206325
TI  - Pharmacokinetic-pharmacodynamic analysis of the arrhythmogenic potency of a novel
      antiallergic agent, ebastine, in rats.
AB  - Ebastine (EBS), a novel nonsedative antiallergic agent, is similar to terfenadine
      in its chemical structure. However, clinical arrhythmogenicity of EBS remains
      controversial. In this study, we evaluated the possible arrhythmogenic potency of
      EBS as assessed by QT prolongation from a pharmacokinetic-pharmacodynamic
      viewpoint in comparison with that of terfenadine. EBS was intravenously infused
      into anesthetized rats at a rate of 3.0 or 10 mg/kg/h for 60 min, and
      electrocardiographic effects were continuously monitored from lead II. The plasma
      concentrations of EBS and its major metabolite, carebastine, were also measured
      under the same conditions. When intravenously administered, EBS exhibited QT
      prolongation in an infusion rate-dependent manner, with a lag time.
      Pharmacokinetic-pharmacodynamic analysis of EBS based on the effect-compartment
      model revealed values of EC50, Emax and EC(10 ms), (where 10 ms of QT
      prolongation was evoked) of 0.73 microg/mL, 12.5 ms and 2.90 microg/mL,
      respectively. The EC(10 ms) value of EBS was five times higher than that of
      terfenadine reported previously (Ohtani et al., J. Pharm. Pharmacol., 49, 458-462
      (1997)). In conclusion, EBS was suggested to be less arrhythmogenic than
      terfenadine.

PMID- 10206326
TI  - Mechanisms of reaction of L-methionine with carboplatin and oxaliplatin in
      different media: a comparison with cisplatin.
AB  - The activity of platinum compounds is dependent on nucleophile substitution
      reactions. In this paper, we study the reactivity of L-met with carboplatin,
      oxaliplatin and cisplatin by following with HPLC-UV the concentration of L-met
      and by characterizing the resulting adducts with LC-MS. In the absence of NaCl,
      in water, the initial rate at which L-met concentration decreases with cisplatin,
      oxaliplatin and carboplatin is 0.25 +/- 0.007, 0.057 +/- 0.01 and 0.17 +/- 0.02
      mM h(-1), respectively. In phosphate buffer this rate is 0.056 +/- 0.009 for
      cisplatin, 0.019 +/- 0.001 and 0.13 +/- 0.02 for carboplatin and oxaliplatin,
      respectively. Reactions of L-met with cisplatin occurred via its conversion into
      monoaqua species in water and into phosphato-derivatives (AP) in phosphate buffer
      but finally the same methionine-platinum adducts M2 [(NH3)2(met)]Pt, M4 and M5
      [(met)2]Pt were characterized. Reaction of carboplatin with L-met occurred via
      the formation of M0 [(NH3)2(met)(CBDCA)]Pt whose structure is consistent with the
      direct interaction of L-met with carboplatin. However, the same final products as
      those found with cisplatin were characterized. The reaction of oxaliplatin with L
      met proceeded through a mechanism similar to that of carboplatin to give M7
      [(met)(DACH)]Pt. In the presence of NaCl, cisplatin directly reacted with L-met
      to yield at least five methionine-platinum adducts. The reaction of carboplatin
      gave the same adducts suggesting its transformation into cisplatin. The reaction
      of oxaliplatin with L-met occurred via the formation of aquated species A
      [(OH)(Cl)(DACH)]Pt which readily underwent reaction with L-met to form M6
      [(met)(Cl)(DACH)]Pt and M7. This study shows that the reactivity of cisplatin,
      carboplatin and oxaliplatin is dependent on the media in which they occur. The
      discrepancy between their reactions with L-met could partly explain their
      therapeutic differences.

PMID- 10206327
TI  - The effect of ammonium glycopyrrolate (Robinul)-induced xerostomia on oral
      mucosal wetness and flow of gingival crevicular fluid in humans.
AB  - The antisialogogue, ammonium glycopyrrolate (Robinul), was used to reduce the
      salivary flow rate in healthy individuals with normal salivary function to
      determine whether the dry-mouth symptoms and reduced amounts and patterns of oral
      mucosal wetness found previously in hyposalivators could be induced by this
      means. After baseline measurements, the drug was given to 10 healthy volunteers
      and their resting whole-saliva flow rate was measured at 0, 15, 60, 105 and 150
      min thereafter. At the same times, the thickness of the layer of residual mucosal
      saliva (a measure of residual mucosal wetness) at each of 22 intraoral sites was
      also determined. The saliva flow rate fell from a mean of 0.45 +/- 0.07 ml/min to
      a mean of 0.05 +/- 0.02 ml/mm by 1 h and slowly thereafter to a mean of 0.02 +/-
      0.01 to 0.03 +/- 0.01 ml/min for the remainder of the experiment. Onset of
      dryness symptoms was observed approx. 30 min after giving the drug.
      Simultaneously, the residual saliva at each of the 22 sites teted decreased to a
      thickness level previously found in patients with hyposalivation and who
      exhibited an intense feeling of dry mouth. Despite these decreases in thickness,
      the pattern of residual mucosal wetness throughout the mouth remained more or
      less unchanged. As in earlier studies, wetness was least on the hard palate and
      highest on the posterior dorsum of the tongue. An altered taste of the residual
      saliva in the mouth and an increased feeling of roughness as the tongue was
      passed over labial and buccal mucosal surfaces were noted. The amount of gingival
      crevicular fluid (GCF) in 12 gingival sites in each of the participants was also
      measured. Unlike the reduction in salivary flow, changes in GCF over the 150 min
      of the study were negligible. From this it was concluded that GCF could
      contribute much more to the oral fluids in dry-mouth than in normal individuals,
      especially when there is greater gingival inflammation.

PMID- 10206328
TI  - Effects of crude venom, tityustoxin and toxin Ts-gamma from Tityus serrulatus
      scorpion on secretion and structure of the rat submandibular gland.
AB  - Changes in the rat submandibular glands after intravenous injections of Tityus
      serrulatus scorpion venom, tityustoxin or toxin Ts-gamma were studied
      histologically and morphometrically. The acini and the granular convoluted
      tubules presented the most prominent changes. The following variables were
      measured: (a) relative volume occupied by the glandular structures; (b) diameter
      of the granular convoluted tubules and thickness of their epithelium; (c)
      diameter of the acini. The cytoplasm of the acinar cells was extensively occupied
      by large confluent vacuoles and had a reduced number of secretory granules after
      intravenous injections of venom or toxins. The morphological changes caused by
      toxin Ts-gamma were greater than those evoked by tityustoxin or crude venom
      injections. In spite of the changes in acinar cells, acinar diameter showed no
      significant alterations after venom or toxin injections. Reduction of diameter
      and depletion of the cytoplasmic secretory granules were observed in the granular
      convoluted tubules 2 h after intravenous injections of crude venom, or after 1 h
      with tityustoxin or toxin Ts-gamma. The intravenous injection of crude venom did
      not induce any visible change in the granular convoluted tubules after 1 h. These
      structural changes could explain the concomitant intense sialagogue effect
      elicited by crude venom, tityustoxin and toxin Ts-gamma. The sialagogue effect
      induced by toxin Ts-gamma was larger than those induced by crude venom or
      tityustoXin.

PMID- 10206329
TI  - Individual variations of pH, buffer capacity, and concentrations of calcium and
      phosphate in unstimulated whole saliva.
AB  - In order to evaluate the risk of development of dental caries and/or of formation
      of dental calculus, salivary variables have often been used, but not with
      particular success. A reason for the apparent lack of association could be that
      the individual temporal variation of a characteristic was so substantial relative
      to the overall variation that it is not possible to characterize an individual by
      a single salivary measurement. The aim here was to examine the individual
      variation of pH, buffer capacity, and concentrations of calcium and phosphate and
      to compare it with the overall variation of the characteristics in order to shed
      light on the above problem. Eight weekly samples of up to 4 ml of unstimulated
      whole saliva were collected from 11 dental students before tooth brushing on
      their arrival at 8 a.m. in the dental school. Calcium was determined by atomic
      absorption spectroscopy, phosphate colorimetrically, and pH electrometrically.
      The buffer capacity was assessed by titration of the saliva sample from the pH
      initially observed to pH 3. It was found that within each individual the
      concentration of calcium and of phosphate, pH, the hydroxyapatite ion product and
      the buffer capacity varied considerably over the 7 weeks. The individual range
      frequently covered more than a third of the total range. Further, within each of
      the variables, single individuals could be found whose samples covered 60% or
      more of the overall range, whilst others covered less than 10% of the range. It
      was therefore concluded that, although collected at the same time of the day, pH,
      buffer capacity and concentrations of calcium and phosphate in unstimulated whole
      saliva in the single individual vary so much that characterization of individuals
      and of their saliva based on a single salivary analysis is unreliable and
      hazardous.

PMID- 10206330
TI  - The roles of histidine residues at the starch-binding site in streptococcal
      binding activities of human salivary amylase.
AB  - Human salivary alpha-amylase participates in the initial digestion of starch and
      may be involved in the colonization of viridans streptococci in the mouth. To
      elucidate the role of histidine residues located near the starch-binding site on
      the streptococcal-binding activity, the wild type and three histidine mutants,
      H52A, H299A and H305A were constructed and expressed in a baculovirus system.
      While His52 is located near the non-reducing end of the starch-binding pocket
      (subsite S3/S4), the residues His299 and His305 are located near the subsites
      S1/S1'. For the wild type, the cDNA encoding the leader and secreted sequences of
      human salivary amylase was amplified by polymerase chain reaction from a human
      submandibular salivary-gland cDNA library, and subcloned into the baculovirus
      shuttle vector pVL1392 downstream of the polyhedrin promoter. Oligonucleotide
      based, site-directed mutagenesis was used to generate the mutants expressed in
      the baculovirus system. Replacing His52 or His299 or His305 to Ala residue did
      not alter the bacterial-binding activity significantly, but these mutants did
      show differences in their catalytic activities. The mutant H52A showed negligible
      reduction in enzymatic activity compared to that of wild type for the hydrolysis
      of starch and oligosaccharides. In contrast, the H299A and H305A mutants showed a
      12 to 13-fold reduction (90-92%) in starch-hydrolysing activity. In addition, the
      k(cat) for the hydrolysis of oligosaccharides by H299A decreased by as much as 11
      fold for maltoheptaoside. This reduction was even higher (40-fold) for the
      hydrolysis of p-nitrophenyl maltoside, with a significant change in K(M). The
      mutant H305A, however, exhibited a reduction in k(cat) only, with no changes in
      the K(M) for the hydrolysis of oligosaccharides. The reduction in the k(cat) for
      the H305A mutant was almost 93% for maltoheptaoside hydrolysis. The pH activity
      profile for the H305A mutant was also significantly different from that of the
      wild type and the other two mutants. These results suggest that, although
      histidines at the starch-binding site of salivary amylase are involved in starch
      binding and catalysis, they may not participate in Streptococcus gordonii G9B
      binding.

PMID- 10206331
TI  - Intra-epithelial lipids in the dorsoposterior area of the tongue in new-born
      rats.
AB  - The mucosa covering the posterior surface of the tongue in new-born rats was
      studied by scanning and transmission electron microscopy. The results
      demonstrated that in the first days of extra-uterine life in the epithelium of
      this mucosa there is an accumulation of lipidic material, which appeared as round
      or oval droplets with a mean diameter of about 0.8-1.0 microm. Their density was
      homogeneously low and they did not contain fibrillar or granular material. In the
      first day of extra-uterine life, the droplets were scarce and mainly localized in
      the dorsal surface of the vallate papilla. In the following days, the lipid
      deposit was present in large areas of the posterior surface of the tongue. At the
      end of the first week of extra-uterine life, as well as in adult animals, the
      lipids were rather scarce. A multilocular lipid deposit was also visible in
      superficial cells detaching from the mucosa. With magnetic resonance
      spectroscopy, lipids extracted from the posterior mucosa of the tongue appeared
      mainly saturated. Small amounts of unsaturated and polyunsaturated lipid were
      also detectable. These findings suggest that in the first week of extra-uterine
      life, specialized areas of the oral epithelium store lipid.

PMID- 10206332
TI  - Expression of hepatocyte growth factor/scatter factor and c-Met in human dental
      papilla and fibroblasts from dental papilla.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF), a broad-spectrum and
      multifunctional cytokine, is essential for the development of tissues including
      tooth. Here it was found that the HGF/SF content of human dental papillae
      obtained from 8 to 16-year-old individuals decreased significantly with age.
      Cultured fibroblasts prepared from the dental papillae of individuals of
      different ages produced HGF/SF at almost the same rate, but the sensitivities of
      the cells to interleukin-1alpha and tumour necrosis factor-alpha for the
      production of HGF/SF increased with age. Generally, mesenchymal cells such as
      fibroblasts produce HGF/SF but do not express c-Met, a receptor for HGF/SF, yet
      fibroblasts in dental papilla and cultured fibroblasts prepared from dental
      papilla did express c-Met, as determined by immunohistochemistry, in situ
      hybridization and reverse transcription-polymerase chain reaction. Recombinant
      human [125I]iodo-HGF/SF specifically bound to cell-surface macromolecules with a
      mol. wt of 146,000, which is the same as that of the beta-subunit of c-Met. The
      physiological role of c-Met on fibroblasts in dental papilla is unknown, but the
      addition of 2 ng of HGF/SF per ml to the culture medium significantly stimulated
      DNA synthesis in the cells, as determined by pulse labelling with [3H]thymidine.
      Exogenous HGF/SF also stimulated secretion by the cells of vascular endothelial
      growth factor, a cytokine that induces blood vessel-formation. These results
      suggest that HGF/SF may be involved in tooth development via autocrine
      mechanisms.

PMID- 10206333
TI  - Stimulation of the dentine-pulp complex of rat incisor teeth by transforming
      growth factor-beta isoforms 1-3 in vitro.
AB  - Expression of transforming growth factor-beta (TGF-beta) isoforms by odontoblasts
      leads to their sequestration within dentine matrix. TGF-beta1 and -beta3
      stimulate matrix secretion and also initiate odontoblast cytodifferentiation in
      vitro and in vivo. Using a recently established organ-culture model, the aim here
      was to examine the effects of TGF-beta isoforms on the response of the dentine
      pulp complex during culture. Agarose beads were soaked in isoforms 1-3, and
      placed on the odontoblast area of slices of 28-day-old rat incisor tooth. The
      slices were maintained in Trowel-type cultures for 7 days. Both TGF-beta1 and 
      beta3 stimulated a local increase in predentine secretion at the site of the bead
      application when compared to control cultures. Mitogenic effects on the cells of
      the subodontoblast layer were also seen and occasionally small foci of newly
      differentiated odontoblast-like cells could be observed a little distant from the
      application site of TGF-beta3. TGF-beta2 had a minimal effect on the cultured
      tissues. These results demonstrate that TGF-beta1 and -beta3 can stimulate
      secretion of extracellular matrix by odontoblasts, are mitogenic to pulp cells,
      and that TGF-beta3 may have inductive effects on pulpal cells. Such activities
      might be important during reparative processes in the dentine-pulp complex after
      tissue injury.

PMID- 10206334
TI  - Possible regulation of epidermal growth factor-receptor tyrosine
      autophosphorylation by calcium and G proteins in chemically permeabilized rat
      UMR106 cells.
AB  - A model using chemically permeabilized cells was developed to examine mechanisms
      that regulate protein tyrosine phosphorylation in osteoblastic cells. Using
      either permeabilized UMR106 osteoblastic or A431 (reference) cells, epidermal
      growth factor (EGF)-induced cellular tyrosine phosphorylation, and whether there
      are previously unrecognized interactions between this transduction pathway and
      Ca2+- or G protein-dependent signalling pathways, were investigated. Both
      permeabilized cell types, when maintained in non-supplemented cytoplasmic
      substitution solution (basic CSS), responded to EGF (1-100 ng/ml) with dose
      dependent increases in tyrosine phosphorylation. A complex and time-dependent
      pattern of phosphotyrosine-containing proteins resulted, but the profile of
      tyrosine phosphorylated proteins was appreciably less complex than in intact
      cells. Supplementation of basic CSS with MgATP restored the normal complexity of
      the profiles for EGF-induced tyrosine phosphorylation proteins in both
      permeabilized cell lines and produced a more sustained accumulation of
      phosphoprotein products in A431 cells. Adding Ca2+ (< or = 10(-6) M), with or
      without exogenous MgATP, dose-dependently attenuated EGF-induced tyrosine
      phosphorylation of EGF receptors (EGFR) and other substrates in UMR106 cells, but
      was less effective in A431 cells. In both cell types, genistein, an inhibitor of
      tyrosine kinases, was more effective in attenuating EGF-induced receptor tyrosine
      phosphorylation in permeabilized cells. Similarly, orthovanadate, an inhibitor of
      protein tyrosine phosphatases, stimulated the accumulation of phosphoprotein
      products more effectively in permeabilized cells. Thus, the permeabilization
      preserves many features of intact cells while facilitating manipulation of
      intracellular conditions. NaF reproducibly produced a significant vanadate-like
      action in permeabilized cells that was somewhat stronger than its effect on
      intact cells. In contrast, the well-known inhibition of tyrosine phosphorylation
      by phorbol 12-myristate 13-acetate (PMA) was less effective in permeabilized
      cells than in intact cells; these actions of PMA were Ca2+-dependent. In
      addition, guanylyl-imidodiphosphate (Gpp(NH)p) attenuated tyrosine
      phosphorylation in UMR106 cells, and this effect was specifically blocked by
      guanosine 5'-O-(2-thiodiphosphate) (GDPbetas). These results strongly suggest
      that there is crosstalk between EGFR-activated tyrosine
      phosphorylation/dephosphorylation pathways and both Ca2+- and G protein-mediated
      pathways in UMR106 cells, revealing a previously unrecognized modulation of EGF
      signalling in osteoblast-like cells that contrasts with the simpler regulatory
      mechanisms found in A431 cells.

PMID- 10206335
TI  - The immunohistochemical localization of the interferon-gamma and granulocyte
      colony-stimulating factor receptors during early amelogenesis in rat molars.
AB  - Previous studies, in which the known janus kinase and signal transducer and
      activator of transcription (STAT) isoforms were immunohistochemically mapped in
      developing rat molars, implicated a sizeable list of cytokine superfamily
      receptor (CSR)/signal-transduction pathway (STP) linkages in the cells of the
      enamel organ involved in the events leading directly to early amelogenesis.
      Various combinations of upregulated janus kinases and STATs are known to be
      linked to single or small groups of CSRs. On the basis of the previous
      observations it was hypothesized that the interferon-gamma receptor (IFNgamma r)
      and the granulocyte colony-stimulating factor receptor (G-CSF receptor) would be
      localized in specific sites in the cells of the enamel organ during early
      amelogenesis. To verify this, whole-head, freeze-dried sections were here
      obtained at the level of the mandibular first and second molar from newborn and 5
      day-old rats. These sections were not demineralized or fixed, reducing the
      possibility of false-negative results. Antibodies to the IFNgamma r and the G-CSF
      receptor were localized using a modification of the avidin-biotin complex method.
      In the newborn rats, IFNgamma r was localized in the preameloblasts in the
      cervical loop, the proximal and distal ends of presecretory ameloblasts, the
      outer enamel epithelium, the dental lamina, and in bone. In 5-day-old rats, it
      was confined to the proximal ends of the presecretory and secretory ameloblasts.
      The G-CSF receptor was observed in the molars of newborn rats in the
      preameloblasts, the proximal and distal ends of the presecretory ameloblasts,
      outer enamel epithelium, and in bone. In 5-day-old rats, G-CSF receptor was
      localized in the preameloblasts, the proximal ends of presecretory and secretory
      ameloblasts, the stellate reticulum, the outer enamel epithelium, and in bone.
      These findings indicate that the IFNgamma r and the G-CSF receptor, and their
      downstream STP linkages, are upregulated in the cells of the enamel organ and may
      be involved in the events leading directly to early enamel formation.

PMID- 10206336
TI  - Cortical distribution of Bereitschaftspotential and negative slope potential
      preceding mouth-opening movements in humans.
AB  - Cortical potentials associated with the voluntary movement of various body parts
      are known as movement-related cortical potentials, which allow evaluation of the
      cortical efferent function and other higher functions controlling voluntary
      movement. The cortical potentials have three main components: the
      Bereitschaftspotential (or 'readiness potential'), the negative slope and the
      motor potential. Here, the cortical potentials preceding mouth-opening movements
      were recorded to investigate which of these components could be observed.
      Electroencephalograms (EEGs) were recorded from 11 electrodes placed over the
      scalp (F3, Fz, F4, T3, C3, Cz, C4, T4, P3, Pz and P4) according to the
      international 10-20 system. Electromyograms (EMGs) were recorded from the
      anterior belly of the digastric and the masseter. The 10 healthy participants
      were requested to make brisk and self-paced mouth-opening movements. All data
      were digitized with a sampling frequency of 200 Hz and stored for off-line
      analysis. Movement-related cortical potentials were obtained by averaging the
      EEG, using the digastric EMG onset as a trigger signal. The
      Bereitschaftspotential was recorded as a gradually increasing, bilaterally
      widespread negativity starting 1.7 s (mean) +/-0.23 s (S.D.) before the onset of
      the opening movement. The amplitude, which was measured at movement onset, was
      maximum at Cz (3.8 +/- 1.3 microV). The negative slope was observed 500-600 ms
      before the movement onset, and the motor potential was not clearly identified,
      because of postmotion artefacts. The cortical maps of the Bereitschaftspotential
      and negative slope combined together before to the mouth opening showed a
      symmetrical distribution with a maximum at the vertex region. The study reveals
      that the Bereitschaftspotential and the negative slope, two components of the
      movement-related cortical potentials, can be observed preceding mouth-opening
      movements and are similar to those associated with other voluntary movements.
      Findings such as distribution, amplitude and onset of the potentials could
      provide important information for studying the cortical control of mandibular
      movements.

PMID- 10206337
TI  - Neurokinin-1 receptor expression in the mature dental pulp of rats.
AB  - Substance P induces inflammatory reactions in peripheral tissues including the
      dental pulp, but its regulatory effects in target tissues are dependent on
      receptor signalling. Here the expression of the substance-P receptor neurokinin-1
      (NK1) in the mature molar pulp of the rat was examined in order to localize the
      main target areas for substance P. A polyclonal antibody directed against the C
      terminal of the receptor was used, and immunohistochemistry was performed by the
      avidin-biotin peroxidase complex method. The results showed that the NK1 receptor
      was intensely expressed along vessel-like structures in the odontoblast and
      subodontoblast layer. A granulated and diffusely distributed NK1-receptor
      labelling was found along larger blood vessels in the root pulp and pulp proper.
      NK1 receptor-positive cells were frequently observed in the cell-rich zone
      beneath the odontoblast layer. The results indicate that, in the mature rat molar
      pulp, the main targets for substance P acting through the NK1 receptors are
      tissues related to blood vessels in the odontoblast and subodontoblast area.
      Furthermore, the expression of NK1 receptors on cells located in the
      subodontoblast area could indicate that substance P also affects cell functions
      in this area.

PMID- 10206338
TI  - Higher activities of acetylcholinesterase and choline acetyltransferase in jaw
      opening than jaw-closing motoneurones in the rat.
AB  - The activities of acetylcholinesterase (AChE) and choline acetyltransferase
      (ChAT) in rat masticatory motoneurones were measured. Anterior digastric (jaw
      opening) and masseter (jaw-closing) motoneurones were retrogradely labelled with
      the fluorescent tracers nuclear yellow and bisbenzimide, respectively. The
      animals were pretreated with an irreversible AChE inhibitor, diisopropyl
      fluorophosphate, for the measurement of AChE activities. After transcardial
      perfusion, serial frozen sections, 20-microm thick, of the brainstem were
      prepared and processed for AChE histochemical analysis. Sections of 30-microm
      thickness were also prepared and processed for ChAT immunohistochemical analysis
      using anti-ChAT antibodies and the peroxidase-antiperoxidase complex. The AChE
      and ChAT activities in motoneurones identified by their fluorescence were
      determined by measuring their absorbance in the cytoplasm at 470 and 450 nm,
      respectively. Each of the enzymatic activities was significantly higher in the
      anterior digastric than in masseter motoneurones (p < 0.001, student t-test).

PMID- 10206339
TI  - Redox regulation of cellular signalling.
AB  - Extracellular stimuli elicit a variety of responses, such as cell proliferation
      and differentiation, through the cellular signalling system. Binding of growth
      factors to the respective receptor leads to the activation of receptor tyrosine
      kinases, which in turn stimulate downstream signalling systems such as mitogen
      activated protein (MAP) kinases, phospholipase Cgamma (PLCgamma) and
      phosphatidylinositol 3-kinase. These biochemical reactions finally reach the
      nucleus, resulting in gene expression mediated by the activation of several
      transcription factors. Recent studies have revealed that cellular signalling
      pathways are regulated by the intracellular redox state. Generation of reactive
      oxygen species (ROS), such as H2O2, leads to the activation of protein tyrosine
      kinases followed by the stimulation of downstream signalling systems including
      MAP kinase and PLCgamma. The activation of PLCgamma by oxidative radical stress
      elevates the cellular Ca2+ levels by flux from the intracellular Ca2+ pool and
      from the extracellular space. Such reactions in the upstream signalling cascade,
      in concert, result in the activation of several transcription factors. On the
      other hand, reductants generally suppress the upstream signalling cascade
      resulting in the suppression of transcription factors. However, it is well known
      that cysteine residues in a reduced state are essential for the activity of many
      transcription factors. In fact, in vitro, oxidation of NFkappaB results in its
      activation, whereas reductants promote its activity. Thus, cellular signalling
      pathways are generally subjected to dual redox regulation in which redox has
      opposite effects on upstream signalling systems and downstream transcription
      factors. Not only are the cellular signalling pathways subjected to redox
      regulation, but also the signalling systems regulate the cellular redox state.
      When cells are activated by extracellular stimuli, the cells produce ROS, which
      in turn stimulate other cellular signalling pathways, indicating that ROS act as
      second messengers. It is thus evident that there is cross talk between the
      cellular signalling system and the cellular redox state. Cell death and life also
      are subjected to such dual redox regulation and cross talk. Death signals induce
      apoptosis through the activation of caspases in the cells. Oxidative radical
      stress induces the activation of caspases, whereas the oxidation of caspases
      results in their inactivation. Furthermore, some cell-death signals induce the
      production of ROS in the cells, and the ROS produced in turn stimulate the cell
      death machinery. All this evidence shows that the cell's fate is determined by
      cross talk between the cellular signalling pathways and the cellular redox state
      through a complicated regulation mechanism.

PMID- 10206341
TI  - Characterization of interactions of Nck with Sos and dynamin.
AB  - One of the adaptor proteins, Nck, comprises a single SH2 domain and three SH3
      domains that are important in protein-protein interactions. The in vivo
      association of Nck with the guanine nucleotide exchange factor Sos has been well
      documented; however, the precise nature of the interaction is unclear. To
      determine which SH3 domains are involved in the Nck-Sos interaction, individual
      SH3 domains of Nck were generated as glutathione S-transferase fusion proteins.
      We found that exclusively the third (C-terminal) SH3 domain of Nck has the
      ability to bind to Sos. In addition, in [35S]methionine labelled K562 cells, a
      100,000 Mr protein was found to be associated with the third SH3 domain of Nck.
      This protein was identified as dynamin, a GTP-binding protein that has been
      implicated in clathrin-coated vesicle formation. Dynamin and Nck co-precipitated
      when cell lysates were immunoprecipitated with anti-Nck antibody. These data
      suggest that Nck may contribute to Ras activation and the function of dynamin in
      membrane trafficking through its third SH3 domain.

PMID- 10206340
TI  - Insulin activates caspase-3 by a phosphatidylinositol 3'-kinase-dependent
      pathway.
AB  - Activation of the caspase proteases by c-Jun N-terminal kinase 1 (JNK1) has been
      proposed as a mechanism of apoptotic cell death. Here we report that insulin
      activates caspase-3 by a pathway requiring phosphatidylinositol 3'-kinase (PI3
      kinase). JNK1 assays demonstrated that insulin treatment of myeloma cells induced
      3-fold activation of JNK1. Inhibition of PI3-kinase with wortmannin and LY294002
      blocked insulin-dependent activation of JNK1. Caspase assays demonstrated that
      insulin increased caspase-3 activity 3-fold and that inhibition of PI3-kinase
      blocked this effect. Cell death was doubled by insulin and was due to a 3-fold
      increase in apoptosis of cells in the G1/G0 phase of the cell cycle. Inhibition
      of PI3-kinase completely blocked this effect. Finally, inhibition of caspase-3
      with benzyloxycarbonyl-Asp-2,6-dichlorobenzoyloxymethylketone blocked cell death
      due to insulin. Taken together, these findings indicate that insulin activates
      caspase-3 by a PI3-kinase-dependent pathway resulting in increased apoptosis and
      cell death.

PMID- 10206342
TI  - Effect of pregnancy on PDE4 cAMP-specific phosphodiesterase messenger ribonucleic
      acid expression in human myometrium.
AB  - In light of the important role of the second messengers cAMP and cGMP in the
      mechanism of relaxation in the human myometrium, specific regulation of the
      phosphodiesterase (PDE) enzymatic system responsible for cyclic nucleotide
      inactivation is essential. We previously identified in the human myometrium PDE4
      cAMP-specific PDE as by far the most abundant isoform. Here we have studied the
      expression patterns of mRNAs for the four cloned human PDE4 genes in the
      myometria of pregnant and non-pregnant women. Concurrent expression of the PDE4A,
      4B, 4C and 4D genes is demonstrated. We found that the PDE4D transcripts are the
      most prominently expressed. PDE4A and PDE4B mRNAs also are markedly abundant,
      whereas lower expression is observed for PDE4C mRNAs. Interestingly, we showed
      that transcripts of PDE4B2 are more abundant in the myometria of pregnant women
      than in non-pregnant women, whereas no difference between the two tissues was
      detected for PDE4A, 4C and 4D mRNAs. Cultured human myometrial cells, which
      present a high level of PDE4 activity and express the four PDE4 mRNA subtypes,
      provide us with an appropriate model to further evaluate whether the level of
      expression of the PDE 4B2 mRNA subtype is under hormonal regulation.

PMID- 10206343
TI  - Effect of ageing on the expression of protein kinase C and its activation by
      1,25(OH)2-vitamin D3 in rat skeletal muscle.
AB  - To characterize age-induced effects on muscle protein kinase C (PKC) and its
      regulation by the steroid hormone 1,25(OH)2-vitamin D3 [1,25(OH)2D3], changes in
      PKC activity and the expression and translocation of the specific PKC
      conventional isoforms alpha and beta, novel isoforms delta, epsilon, and theta
      and atypical isoform zeta were studied in homogenates and subcellular fractions
      from skeletal muscle of young (3 months) and aged (24 months) rats treated in
      vitro with 1,25(OH)2D3. The hormone (10(-9) M) increased total and membrane PKC
      activity, within 1 min, and these effects were completely blunted in muscle from
      aged rats. The presence of PKC isoenzymes was shown by Western blot analysis with
      the use of specific antibodies. The expression of PKC alpha, beta and delta was
      greatly diminished in old rats, whereas age-related changes were less pronounced
      in the isoforms epsilon, theta and zeta. After a short exposure (1 min) of muscle
      to 1,25(OH)2D3, increased amounts of PKC alpha and beta in muscle membranes and
      reverse translocation (from membrane to cytosol) of PKC epsilon were observed
      only in young animals. The data indicate that, in rat muscle, ageing impairs
      calcium-dependent PKC (alpha and beta) and calcium-independent PKC (delta,
      epsilon, theta and zeta) signal transduction pathways under selective regulation
      by 1,25(OH)2D3.

PMID- 10206344
TI  - Inhibition of GTPgammaS-dependent L-isoaspartyl protein methylation by tyrosine
      kinase inhibitors in kidney.
AB  - Protein carboxyl methylation in rat kidney cytosol is increased by the addition
      of guanosine 5'-O-[gamma-thio]triphosphate (GTPgammaS), a non-hydrolysable
      analogue of GTP. GTPgammaS-stimulated methyl ester group incorporation takes
      place on isoaspartyl residues, as attested by the alkaline sensitivity of the
      labelling and its competitive inhibition by L-isoaspartyl-containing peptides.
      GTPgammaS was the most potent nucleotide tested, whereas GDPbetaS and ATPgammaS
      also stimulated methylation but to a lesser extent. Maximal stimulation (5-fold)
      of protein L-isoaspartyl methytransferase (PIMT) activity by GTPgammaS was
      reached at a physiological pH in the presence of 10 mM MgCl2. Other divalent
      cations, such as Cu2+, Zn2+ and Co2+ (100 microM), totally inhibited GTPgammaS
      dependent carboxyl methylation. The phosphotyrosine phosphatase inhibitor
      vanadate potentiated the GTPgammaS stimulation of PIMT activity in the kidney
      cytosol at a concentration lower than 40 microM, but increasing the vanadate
      concentration to more than 40 microM resulted in a dose-dependent inhibition of
      the GTPgammaS effect. The tyrosine kinase inhibitors genistein (IC50 = 4 microM)
      and tyrphostin (IC50 = 1 microM) abolished GTPgammaS-dependent PIMT activity by
      different mechanisms, as was revealed by acidic gel analysis of methylated
      proteins. Whereas tyrphostin stabilised the methyl ester groups, genistein acted
      by blocking a crucial step required for the activation of PIMT activity by
      GTPgammaS. The results obtained with vanadate and genistein suggest that tyrosine
      phosphorylation regulates GTPgammaS-stimulated PIMT activity in the kidney
      cytosol.

PMID- 10206345
TI  - Synergistic effect of arachidonic acid and cyclic AMP on glucose transport in 3T3
      L1 adipocytes.
AB  - The combined effect of arachidonic acid and cAMP on glucose transport was
      examined in 3T3-L1 adipocytes. In cells pre-treated with arachidonic acid and
      increasing concentrations of 8-bromo cAMP for 8 h, although either agent alone
      enhanced glucose uptake, the simultaneous presence of both agents dramatically
      increased 2-deoxyglucose uptake in a synergistic fashion. Insulin-stimulated
      glucose transport, on the other hand, was only slightly affected. The synergistic
      effect of these two agents was abolished in the presence of cycloheximide.
      Immunoblot analysis revealed that the contents of ubiquitous glucose transporter
      (GLUT1) in total cellular and plasma membranes were similarly augmented in cells
      pre-treated with both arachidonic acid and 8-bromo cAMP, to a greater extent than
      the additive effect of each agent alone. The content of GLUT4, on the other hand,
      was not altered under the same experimental conditions. In cells pre-treated with
      4beta-phorbol 12beta-myristate 13alpha-acetate (PMA) for 24 h to down-regulate
      protein kinase C (PKC), the subsequent synergistic effect of arachidonic acid and
      8-bromo cAMP was greatly inhibited. In addition, pre-treatment with both PMA and
      8-bromo cAMP enhanced glucose transport in a similarly synergistic fashion. Thus
      the present study seems to indicate that arachidonic acid may act with cAMP in a
      synergistic way to increase glucose transport by a PKC-dependent mechanism. The
      increased activity may be accounted for by increased GLUT1 synthesis.

PMID- 10206346
TI  - Investigation of S-farnesyl transferase substrate specificity with combinatorial
      tetrapeptide libraries.
AB  - Using biased tetrapeptide libraries made up of proteinogenic amino acids of the
      general formula Cys-O2-X3-X4, we searched for new substrates of partly purified
      rat brain S-farnesyl transferase (FTase). To achieve this task, an assay was
      developed in which the consumption of the co-substrate (farnesyl pyrophosphate)
      was measured. After three steps of deconvolution including each synthesis and
      enzymatic assay, the most efficient substrates found under these particular
      conditions were Cys-Lys-Gln-Gln (peptide I) and Cys-Lys-Gln-Met (peptide II). As
      a control, we used another tetrapeptide library (Cys-Val-O3-X4) in which the
      valine position was arbitrarily fixed, corresponding to Cys-Val-Ile-Met in the
      CAAX box of K-RasB, although this sublibrary was only marginally active compared
      with Cys-Lys-X3-X4 in the first round of deconvolution. The best substrate
      sublibrary was Cys-Val-Thr-X4, threonine being more favourable than the aliphatic
      amino acids (Val, Ile, Leu, Ala) in this position. Deconvolution finally led to
      Cys-Val-Thr-Gln, -Met, -Thr and -Ser as the most efficient substrates of FTase.
      Those tetrapeptides were not substrates of a partly purified geranylgeranyl
      transferase 1 (GGTase1). We also investigated the influence of the -1 position
      (at the N-terminus of cysteine) on the specificity of the enzyme, by using a
      series of pentapeptides constructed on the basis of the best tetrapeptide core
      (peptide 1). Among this family of analogues, only His-Cys-Lys-Gln-Gln did not
      behave as a substrate, whereas all the other pentapeptides were measurable
      substrates, with Gly-, Asn- and Thr-Cys-Lys-Gln-Gln displaying kinetic constants
      similar to that of Cys-Lys-Gln-Gln. The present work provides strong evidence
      that the best tetrapeptide substrates of FTase do not necessarily belong to the
      classical CAAX box, in which A's are lipophilic residues, but rather contain
      hydrophilic amino acids in the middle of their sequences. Among them, peptides I
      and II are potent FTase in vitro substrates that are not recognised by GGTase1
      and might be new starting points for the design of FTase inhibitors.

PMID- 10206347
TI  - Involvement of protein kinase C and rho GTPase in the nuclear signalling pathway
      by transforming growth factor-beta1 in rat-2 fibroblast cells.
AB  - The transforming growth factor (TGF)-beta signal-transduction cascade from the
      cell membrane to the nuclear target is poorly characterised. Here we report that
      treatment with TGF-beta1 induces the levels of endogenous c-fos mRNA in Rat-2
      fibroblast cells. In addition, by transient transfection analysis, TGF-beta1 was
      shown to stimulate c-fos serum response element (SRE)-driven reporter gene
      activity in a dose- and time-dependent manner, suggesting that SRE is one of the
      nuclear targets of TGF-beta1. To understand the signalling cascade by which TGF
      beta1 mediates the transactivation of c-fos SRE, cells were either pre-treated
      with various inhibitors or co-transfected with expression plasmids encoding
      inhibitory proteins for Rho GTPase together with the SRE-luciferase reporter
      gene. Our results showed that an inhibition of protein kinase C (PKC) or RhoA
      selectively repressed the stimulation of c-fos SRE by TGF-beta1, implying the
      possible roles of PKC and RhoA GTPase in TGF-beta1-induced signalling to c-fos
      SRE.

PMID- 10206348
TI  - Handicap questionnaires: what do they assess?
AB  - BACKGROUND AND PURPOSE: There is an increasing need to get insight into the
      social and societal impact of chronic conditions on a person's life, i.e. person
      perceived handicap. The purpose of this study is to report how current handicap
      questionnaires assess handicap. METHOD: A literature search using both Medline
      and the database of the Dutch Institute of Allied Health Professions (NPi) was
      conducted for handicap questionnaires. Questionnaires were included if addressing
      handicaps or life roles, environmental influences and social consequences of a
      disease. Excluded were questionnaires focusing on only impairments, disabilities
      or quality of life. RESULTS AND CONCLUSION: 20 questionnaires were identified.
      Handicap is not uniformly defined in these questionnaires. Based on different
      concepts, the various questionnaires encompass different domains and different
      aspects are emphasized in similar domains. Fourteen questionnaires assess society
      perceived handicaps, and do not address the life roles, care needs or individual
      problem-experience. Six questionnaires are to some extent person-perceived, but a
      generic person-perceived handicap questionnaire could not be identified. It is
      concluded that development of a generic person-perceived handicap questionnaire
      is essential for adequate assessment of needs, outcome, and relevance of
      rehabilitation interventions from the individual's point of view.

PMID- 10206349
TI  - The categorization and control of people with disabilities.

PMID- 10206350
TI  - Screening by nurses for aphasia in stroke--the Ullevaal Aphasia Screening (UAS)
      test.
AB  - PURPOSE: In Norway, the speech therapist is responsible for the assessment of
      language impairment after stroke, but many hospitals have no speech therapist.
      This study therefore developed and evaluated a simple method to be used by nurses
      to detect aphasia in the acute stage of stroke; the Ullevaal Aphasia Screening
      (UAS) test. METHOD: The study was carried out among 37 stroke patients admitted
      to an acute stroke unit. They were assessed by nurses using the UAS, while the
      results of a comprehensive assessment by a speech therapist acted as the 'gold
      standard'. RESULTS: The predictive value of a positive test was 0.67 and that of
      a negative test 0.93; only two out of 28 who screened negative on the UAS were
      diagnosed with mild aphasia by the speech therapist. The weighted kappa
      coefficient of agreement was 0.83, indicating a strong agreement between the
      nurses' and speech therapists' scoring. The screening took 5-15 minutes to
      complete. CONCLUSION: The Ullevaal Aphasia screening test seems to be a short and
      valid screening instrument for aphasia in the acute stage of stroke, but further
      studies would be needed to substantiate the efficacy of the UAS test.

PMID- 10206351
TI  - Handicap in stroke survivors.
AB  - BACKGROUND AND PURPOSE: As survival following stroke improves, individuals are
      more likely to live with the aftermath of stroke rather than immediately die from
      it. The purpose of this study was to examine the consequences of stroke on the
      life activities of survivors in the social realm (stroke handicap) using the
      framework of the World Health Organization's International Classification of
      Impairments, Disabilities and Handicaps. METHODS: Multivariate analysis of
      variance was applied to cross-sectional data from a clinical study to investigate
      the correlates of handicap in a cohort of hemispheric stroke survivors at 3
      months (n = 145) and at 1 year (n = 135) after stroke onset. Handicap was
      assessed with the Reintegration to Normal Living Index, impairment by the Adams'
      Hemispheric Stroke Scale and Zung Depression Scale, and disability by the
      Functional Independence Measure. Environmental variables in the model included
      marital status and receipt of rehabilitation therapy. RESULTS: Physical
      disability and post-stroke depressive symptoms were associated with handicap at
      both follow-up periods (p < 0.05). Cognitive disability and impairments from a
      previous stroke were also associated with handicap (p < 0.01), but only at 1
      year. The presence of a spouse was found to benefit male survivors at 1 year.
      CONCLUSIONS: Disability and depressive symptoms restrict the meaningful life
      activities of stroke survivors in the first year of recovery. Social supports may
      be influential in reducing their impact.

PMID- 10206352
TI  - Using an orientation system for indoor travel and activity with persons with
      multiple disabilities.
AB  - PURPOSE: The study assessed the effectiveness of an orientation system,
      consisting of a programmable control device linked to acoustic and light sources,
      for facilitating independent indoor travel and activity in two persons with
      profound intellectual disability and blindness or severe visual impairment.
      METHOD: The control device was programmed to activate each destination the
      persons were to reach and the acoustic or light sources leading to it
      automatically (i.e. after a preset time from the persons reaching the previous
      destination). One person was exposed to two baseline phases without the system
      being alternated with two orientation phases with the system; the other person
      received only one baseline and one orientation phase. RESULTS: Data showed that
      during the orientation phases, both persons benefited from the use of the system
      and could reach the destinations successfully and carry out the activities.
      CONCLUSIONS: The possibility of promoting independent indoor travel and activity
      in persons with multiple disabilities may have important implications for the
      condition of these persons and for rehabilitation and care centres.

PMID- 10206353
TI  - A scientific perspective on developing acupuncture as a complementary medicine.

PMID- 10206354
TI  - Acupuncture: neurophysiological perspectives.

PMID- 10206355
TI  - Critical perspectives.

PMID- 10206356
TI  - Methodological perspectives.

PMID- 10206357
TI  - Re: Dickson HG. Re: Dickson's problems with the ICIDH definition of impairment.
      Disability and Rehabilitation 1997; 19, 122-123.

PMID- 10206359
TI  - Speech sound perception, neurophysiology, and plasticity.
AB  - An approach to understanding biological processes underlying speech perception,
      is to discover how speech sounds are represented in the central auditory system
      and to relate that representation to the perception of speech as a meaningful
      acoustic signal. Research from our group that pertains to the neurophysiologic
      representation of speech in the central pathways is reviewed here. Specifically
      considered is the relation between the representation of sound in the auditory
      pathway and the perception/misperception of speech, and neurophysiologic
      plasticity associated with speech-sound perceptual learning.

PMID- 10206360
TI  - Neuro-functional imaging and profound deafness.
AB  - This paper deals with the subject of the place of neuro-functional imaging in
      cochlear implantation. Neuro-functional imaging is a means to assess the
      functioning of the brain in some normal or pathological conditions. Deafness is a
      model of sensorineural deprivation. Cochlear implantation offers to clinicians
      and neuroscientists a model for understanding influence of deafness on cerebral
      connectivity, and to assess mechanisms of plasticity when the auditory inputs are
      given again to a deaf cochlea. This paper proposes a brief review of the
      literature on cochlear implantation and neuro-functional imaging. Patients can be
      scanned pre- or post-operatively, thus different questions can be investigated
      about neurobiology of the consequences of deafness and auditory rehabilitation by
      cochlear implantation, and about the possible role of neuro-functional imaging in
      cochlear implant candidates to predict the future benefit of the implantation.

PMID- 10206361
TI  - Necessity versus sufficiency: the role of input in language acquisition.
AB  - There is data which indicates that the critical/sensitive period(s) for language
      development begins in the 6th month of fetal life and may be most susceptible to
      impairment during the first 2 years of life. There are observations which would
      indicate that the linguistic abilities which develop are dependent upon the
      amount of linguistic information available to the infant and are not dependent
      upon any particular receptive sensory mode. The challenge for the cochlear
      implant is to be able to transmit sufficient linguistic information--flux of
      information--during this period so that the resultant language is optimal.
      Language must be the primary outcome measure of the cochlear implant in the
      infant and young child.

PMID- 10206362
TI  - Paediatric cochlear implantation and health-technology assessment.
AB  - Cochlear implants are provided to children on the basis of the hypothesis that
      short-term outcomes in auditory receptive skills will translate via a cascade of
      medium-term outcomes into greater social independence and quality of life. The
      medium-term outcomes include: (i) enhanced engagement and integration in primary
      education, leading to greater scholastic achievement; (ii) enhanced social
      versatility and robustness, permitting a successful transition to secondary
      education; and (iii) enhanced educational qualifications, allowing greater
      opportunities in further education and employment. A sufficient number of
      children have used implants for long enough for it to be feasible to establish
      whether the first two medium-term outcomes are being achieved and, if so, at what
      cost in the provision of health care and education. The first part of this paper
      discusses alternative research designs that could address these issues. Although
      a prospective randomised controlled trial would provide the most powerful
      evidence for or against the hypothesis, it is implausible that adequate
      compliance with randomisation to treatments could be sustained to give such a
      study sufficient power. The most powerful realisable design would be a large
      scale cross-sectional comparison of implanted children and matched groups of
      their non-implanted peers. The second part of the paper describes the results of
      a speculative cost-benefit analysis that seeks to identify the cost to society of
      providing implants to children. The analysis is based on measured costs of health
      care, but on estimates of costs and cost-savings in other domains. It indicates
      that paediatric implantation could be cost-neutral in the UK, provided that
      implantation saved pound sterling 3000/year in the cost of education, pound
      sterling 1000/year in other domains, and permitted an increase in personal income
      of 25% of the national median household income. These savings might be realised
      if implantation permitted sufficient facility in spoken language to allow every
      implanted child to enter mainstream education.

PMID- 10206363
TI  - Oral language acquisition in children assessed with the Reynell Developmental
      Language Scales.
AB  - Oral language development of ten children, prelingually deafened by meningitis,
      was assessed with a Dutch version of the Reynell Developmental Language Scales.
      The test was administered pre-operatively and at regular intervals after
      implantation. The average rate of language development between two consecutive
      evaluations was computed. This rate was defined as the quotient of the increase
      of the language age and the increase of the chronological age between the
      evaluations. A normal language development has a rate of 1; this means 12 months
      language development in 12 months time. In case of language retardation the rate
      of language development is less than 1. The rate of receptive language
      development showed a gradual increase. In the interval between 12 and 24 months
      of implant use the ratio was 0.9. This implies a language development that is
      quite similar with the development in normal hearing children. The rate of
      expressive language development showed a fast improvement in the period between 6
      and 12 months after implantation, up to 1.4. If this rate of development
      continues the children with C.I. will catch up with their normal hearing peers.

PMID- 10206364
TI  - Phonological representations in postlingual deaf subjects using a multichannel
      cochlear implant.
AB  - Our research is a first attempt to study phonological representations in
      postlingually deaf subjects using a multichannel cochlear implant. Before
      deafness, these subjects had developed normal language. The present study
      investigated how phonological representations are assessed through cochlear
      implant inputs by comparing priming within the auditory modality, and priming in
      a visual-auditory, cross-modal, condition. Two postlingually deafened adults
      participated in two lexical decision experiments where word primes were
      phonologically paired with a word target (e.g. vedette/dette), or a pseudoword
      target (e.g. banane/nane). The same word primes were also paired with non
      phonologically related target words (e.g. vedette/chat) and pseudowords (e.g.
      banane/repe). In addition, the same targets were used in phonologically-related
      pairs and in phonologically-unrelated ones. Results showed different priming
      effects for each patient. In one patient, priming was observed for word targets
      in the unimodal condition only. In the other patient, priming was observed for
      word targets and interference was observed for pseudoword targets in the cross
      modal condition, whereas no effect was observed in the unimodal condition. In
      addition, this last patient made more errors for pseudowords than for words in
      the cross-modal condition. These results were interpreted as suggesting that
      lexical phonological representations participated to priming effects. Moreover,
      our results suggest that phonological word forms can be activated by visual
      primes via cochlear implants.

PMID- 10206365
TI  - Speech recognition, speech production and speech intelligibility in children with
      hearing aids versus implanted children.

PMID- 10206366
TI  - Preconditions of language development in deaf children.
AB  - The harmful effects of childhood hearing impairment are given little thought by
      many people because hearing loss is largely an invisible handicap. An infant with
      a hearing impairment is generally healthy-looking and develops relatively
      normally during the first year of life. Hearing impairment in infants interferes
      with the normal development of spoken language. We are biologically programmed to
      develop certain skills in response to certain inputs. Language learning is one
      such skill which must be gained very early in life. Hearing is the most important
      basis for normal language acquisition and language is the keystone of modern
      society. Hearing loss must be identified as early as possible in the first years
      of life, especially a child with profound or severe hearing loss must be
      identified in the first year of life. If not, the child has missed an
      irreversible sensitive phase for learning of speech and language.

PMID- 10206367
TI  - Development of speech in 2-year-old children with cochlear implant.

PMID- 10206368
TI  - Evaluation of cochlear implanted children's voices.
AB  - Cochlear implant (CI) is a good means in developing communication in deaf
      children. Nevertheless, compared to children with the same age, CI patients'
      voices are far from being similar. In this work, the voice of CI children has
      been compared with the voice of corresponding normal children (same age, same
      sex) included in the main stream. Six girls and two boys participated to the
      experiment. The phonetic material was a paragraph of the French standard text La
      bise et le soleil (The North Wind and the Sun). An objective and a subjective
      analysis of the voice were done and parameters were compared between both groups
      of people (implantees and control). Studied parameters were voice pitch,
      intensity, fluency, pauses, articulation and pleasantness in the objective
      analysis, and voice pitch, formants, and duration for the objective study. It
      appeared that intensity variations were different between control and implanted
      subjects. Also voice formants were not situated in the same region regarding the
      normal ranges, but differences were difficult to assess. Globally, the main
      change was in the speaking duration. This method is open for further studies and
      points out some relevant items for an efficient use in rehabilitation sessions.

PMID- 10206369
TI  - 'Small group' rehabilitation in adolescent cochlear implant users: learning
      experiences.
AB  - The reasons for which a group approach has been chosen for the small group
      rehabilitation of adolescent cochlear implant users are discussed. The most
      significant learning experiences after 18 months of treatment were the
      socialization of experience, the socialization of individual learning processes,
      the direct relationship between adolescents, practice discussion of topics of
      common interest, emphasizing of personal opinions and beliefs, experiencing
      collective 'products', the reinforcement of interpersonal relationships and the
      emphasizing of individual initiatives both at home and at school.

PMID- 10206370
TI  - 'Small group' rehabilitation in adolescent cochlear implant users: aims, method
      and results.
AB  - The aim was to extend the linguistic, social and cognitive aspects of
      communication skills. The method was to use meaningful contexts and to attribute
      new significance to errors. Methods used were phonetic games (to improve speech
      production) and exercises (to increase reading and writing skills). The results
      after 18 months of group rehabilitation are presented.

PMID- 10206371
TI  - Communication outcomes after paediatric cochlear implantation.

PMID- 10206372
TI  - Auditory training in severely and profoundly hearing impaired toddlers: the
      development of auditory skills and verbal communication.
AB  - Three different tests are applied to evaluate the performance of very young
      hearing impaired children. Three subgroups were formed according to hearing loss.
      The sound identification test as well as the Reynell Developmental Scales proved
      to be useful but Early Scales of Communication did not differentiate well enough
      between the three subgroups.

PMID- 10206373
TI  - Cued speech in the stimulation of communication: an advantage in cochlear
      implantation.

PMID- 10206374
TI  - Cochlear implants and sign language.

PMID- 10206375
TI  - Summary of the International Conference on Language Development in Cochlear
      Implanted Children, Lyon, France, 8-9 December 1996.

PMID- 10206376
TI  - Drugs for ventricular arrhythmias in the era of the implantable cardioverter
      defibrillator.

PMID- 10206377
TI  - Pulmonary venous flow analysis after cardioversion.

PMID- 10206378
TI  - Foreseeing complications of coronary angioplasty--predicting the unpredictable.

PMID- 10206379
TI  - Effects of acute ischaemia on intramyocardial contraction heterogeneity; new
      ultrasound technologies to study an old phenomenon.

PMID- 10206380
TI  - Sudden death in the working population: a collaborative study in central Japan.
AB  - AIM: Few epidemiological data are available describing the sudden death of
      persons in their prime. This study aims to elucidate when and how sudden death
      occurs among employees. METHODS: A total of 196775 employees from 10 workplaces
      in Central Japan were surveyed for non-traumatic sudden death during 1989-1995.
      Demographic data and information regarding onset were collected by their
      workplace healthcare professionals. RESULTS: We identified 251 male and 13 female
      cases of sudden death. The annual incidence was 21.9 (for men) and 5.7 (for
      women) per 100000 population. Sudden death occurred more frequently in April when
      the new business year starts (risk ratio [95% confidence interval], 1.62 [0.94
      2.79]) than in other months, without seasonality. Sudden death peaked on Sundays
      (risk ratio, 1.90 [1.20-2.99]) and Saturdays (risk ratio, 1.36 [0.83-2.21]) as
      compared with weekdays, and was likely to occur in the small hours (risk ratio,
      1.71 [0.94-3.10] at 00-0300 h and 1.47 [0.79-2.72] at 0300-0600 h vs at 0900-1200
      h. Only 17% of employees died at work, which was significantly less than expected
      (P<0.001). CONCLUSION: These findings differed from those of elderly people and
      suggest that sudden death of persons in their prime is related to occupational
      stress and its relief.

PMID- 10206381
TI  - Relationship between smoking and cardiovascular risk factors in the development
      of peripheral arterial disease and coronary artery disease: Edinburgh Artery
      Study.
AB  - AIMS: The aim was to determine whether the effect of smoking on the development
      of peripheral or coronary artery disease might be mediated by other
      cardiovascular risk factors, including dietary antioxidant vitamin intake, serum
      low and high density lipoproteins, blood pressure, plasma fibrinogen, blood
      viscosity and markers of endothelial disturbance and fibrin turnover. METHODS AND
      RESULTS: 1592 men and women aged 55-74 years were selected at random from 11
      general practices in Edinburgh, Scotland and followed-up for 5 years. The
      incidences of peripheral arterial disease and coronary artery disease were 5.1%
      and 11.1%, respectively. Both conditions were more common in moderate and heavy
      smokers than in never smokers: cigarette smoking was a stronger risk factor for
      peripheral arterial disease than for coronary artery disease. Smoking was
      associated with reduced dietary antioxidant vitamin intake, serum high density
      lipoprotein cholesterol and diastolic blood pressure and with increased alcohol
      intake, serum triglycerides, blood viscosity, plasma fibrinogen, and markers of
      endothelial disturbance (tissue plasminogen activator and von Willebrand factor
      antigens). Simultaneous adjustment for these risk factors reduced the relative
      risk of peripheral arterial disease only slightly, from 3.94 (95% CI 2.04, 7.62)
      to 2.72 (95% CI 1.13, 6.53) in heavy smokers and from 1.87 (95% CI 0.91, 3.85) to
      1.70 (95% CI 0.72, 3.99) in moderate smokers. Similar adjustment also had little
      effect on the risk of coronary artery disease associated with smoking.
      CONCLUSION: The combined effect of smoking on the cardiovascular risk factors
      studied may explain part of its influence on peripheral and coronary arterial
      disease, but the majority of the effect appears to be due to other mechanisms.

PMID- 10206382
TI  - A prognostic computer model to individually predict post-procedural complications
      in interventional cardiology: the INTERVENT Project.
AB  - AIMS: The purpose of this part of the INTERVENT project was (1) to redefine and
      individually predict post-procedural complications associated with coronary
      interventions, including alternative/adjunctive techniques to PTCA and (2) to
      employ the prognostic INTERVENT computer model to clarify the structural
      relationship between (pre)-procedural risk factors and post-procedural outcome.
      METHODS AND RESULTS: In a multicentre study, 2500 data items of 455 consecutive
      patients (mean age: 61.1+/-8.3 years: 33-84 years) undergoing coronary
      interventions at three university centres were analysed. 80.4% of the patients
      were male, 16.7% had unstable angina, and 5.1%/10.1% acute/subacute myocardial
      infarction. There were multiple or multivessel stenoses in 16.0%, vessel bending
      >90 degrees in 14.5%, irregular vessel contours in 65.0%, moderate calcifications
      in 20.9%, moderate/severe vessel tortuosity in 53.2% and a diameter stenosis of
      90%-99% in 44.4% of cases. The in-lab (out-of-lab) complications were: 0.4%
      (0.9%) death, 1.8% (0.2%) abrupt vessel closure with myocardial infarction and
      5.5% (4.0) haemodynamic disorders. CONCLUSION: Computer algorithms derived from
      artificial intelligence were able to predict the individual risk of these post
      procedural complications with an accuracy of >95% and to explain the structural
      relationship between risk factors and post-procedural complications. The most
      important prognostic factors were: heart failure (NYHA class), use of
      adjunctive/alternative techniques (rotablation, atherectomy, laser), acute
      coronary ischaemia, pre-existent cardiac medication, stenosis length, stenosis
      morphology (calcification), gender, age, amount of contrast agent and smoker
      status. Pre-medication with aspirin or other cardiac medication had a beneficial
      effect. Techniques, such as laser angioplasty or atherectomy were predictors for
      post-procedural complications. Single predictors alone were not able to describe
      the individual outcome completely.

PMID- 10206383
TI  - Comparison of sotalol with amiodarone for long-term treatment of spontaneous
      sustained ventricular tachyarrhythmia based on coronary artery disease.
AB  - AIM: To compare the efficacy of sotalol versus amiodarone for long-term treatment
      of ventricular tachyarrhythmias. METHODS: Patients (n=75) with spontaneous,
      sustained ventricular tachyarrhythmias secondary to remote myocardial infarction
      were studied. After intravenous electrophysiological testing, both sotalol and
      amiodarone were predicted to be ineffective in 50 (67%) patients. Five patients
      were excluded. Forty-five patients were randomized to receive sotalol (n=22) or
      amiodarone (n=23) for maintenance therapy. The primary outcome variable was the
      time to first recurrence of sustained ventricular tachyarrhythmia. RESULTS: At 36
      months. 75% of those allocated sotalol remained free of ventricular
      tachyarrhythmia compared with 38% of those allocated amiodarone (P=0.05). On
      multivariate analysis the risk of recurrence of ventricular tachyarrhythmia for
      patients on amiodarone was 5.9 times higher (P=0.008) than that for patients on
      sotalol. CONCLUSION: Sotalol is superior to amiodarone for long-term treatment of
      ventricular tachyarrhythmia secondary to coronary artery disease when both drugs
      have been predicted to be ineffective at intravenous electrophysiological
      testing. Randomized trials in larger numbers of patients with ventricular
      tachyarrhythmia need to be performed comparing the two agents directly.

PMID- 10206384
TI  - Pulmonary vein flow analysis by transoesophageal echocardiogr phy in patients
      with chronic atrial fibrillation; 1 year follow-up after cardioversion.
AB  - AIMS: Left and right upper pulmonary vein flow can be adequately recorded by
      transoesophageal Doppler echocardiography. The aim of this study was to
      investigate whether analysis of the pulmonary venous flow velocity pattern can
      predict the long-term maintenance of sinus rhythm after successful cardioversion
      of chronic atrial fibrillation. METHODS AND RESULTS: Thirty-six consecutive
      patients, aged 53+/-9 years, with chronic atrial fibrillation of 5.33+/-2 months
      duration, were subjected to transoesophageal Doppler echocardiography to record
      left and right upper pulmonary venous flow, 24 h and 3 months following
      successful cardioversion. One year following cardioversion, 12 patients (33.3%)
      were in sinus rhythm (sinus rhythm group) while the remaining 24 patients were in
      atrial fibrillation (atrial fibrillation group). At 24 h following cardioversion,
      biphasic systolic forward flow in the left and/or right upper pulmonary venous
      flow velocity was detected in 10 patients of the sinus rhythm group and in four
      patients of the atrial fibrillation group (P<0001). The systolic fraction was
      significantly higher in the sinus rhythm group, 0.48+/-0.04 and 0.39+/-0.06,
      P<0.001 for the left upper pulmonary venous flow, and 0.52+/-0.05 and 0.41+/
      0.04, P<0.001 for the right upper pulmonary venous flow, respectively. In
      patients who displayed a biphasic systolic forward flow and in whom the right
      upper pulmonary venous flow systolic fraction was higher than 0.50 at 24 h post
      cardioversion, the probability of maintenance of sinus rhythm at 1 year exceeded
      95%. CONCLUSION: The detection of a biphasic systolic forward flow in the
      pulmonary venous flow velocity, and of a right upper pulmonary vein systolic
      fraction higher than 0.50 as early as 24 h following cardioversion of chronic
      atrial fibrillation, identifies patients who will remain in sinus rhythm 1 year
      after cardioversion.

PMID- 10206385
TI  - Prevalence and significance of left ventricular outflow gradient during
      dobutamine echocardiography.
AB  - AIMS: This study investigated the clinical and physiological significance of the
      dynamic left ventricle outflow gradient observed in some patients during
      dobutamine stress echocardiography. METHODS: Three hundred and ninety-four
      consecutive patients completed dobutamine stress echocardiography using Doppler
      echocardiography to assess the presence of myocardial ischaemia and left
      ventricular outflow gradient. The prevalence of left ventricular outflow gradient
      was evaluated and correlated with echocardiographic and clinical findings.
      Fifteen patients with left ventricular outflow gradient during dobutamine
      infusion underwent exercise echocardiography for appearance of left ventricular
      outflow gradient. RESULTS: Sixty-nine of 394 (17.5%) patients developed a left
      ventricular outflow gradient of more than 36 mmHg. In nine of them (13%) the
      anterior mitral valve leaflet had a systolic anterior motion. In 60 of the 69
      patients (87%) there was a dynamic obstruction at the level of the papillary
      muscles. The mean intracavitary gradient was 75.4 (range 36-175) mmHg. There was
      no correlation between the presence or absence of a dobutamine stress
      echocardiography-induced left ventricle outflow gradient and chest pain or
      shortness of breath. In patients who developed a left ventricular outflow
      gradient ischaemic wall motion abnormalities occurred at a significantly lower
      frequency during dobutamine stress echocardiography (2.9 vs 16.4% P<0.001). None
      of the 15 patients who underwent exercise echocardiography developed significant
      left ventricular outflow gradient. CONCLUSION: Left ventricular outflow gradient
      occurs occasionally during dobutamine stress echocardiography examination. Its
      presence is of no physiological or clinical significance.

PMID- 10206386
TI  - Diagnosing heart failure.

PMID- 10206387
TI  - Change in electrical stimulation regimen after cardiomyoplasty.

PMID- 10206388
TI  - Outpatient care programmes for the elderly.

PMID- 10206389
TI  - Effects of tonsillectomy and/or adenoidectomy on vocal function: laryngeal,
      supralaryngeal and perceptual characteristics.
AB  - A prospective, non-randomized study evaluated the effects of tonsillectomy and/or
      adenoidectomy (T +/- A) on acoustic and perceptual aspects of vocal function.
      Thirty-one children, ranging in age from 4 to 15 years participated and
      measurements were made prior to and 3 months following surgery. Twenty-three
      children had T +/- A and eight had adenoidectomy alone. Quantitative acoustic
      measures included: laryngeal (vocal fundamental frequency, FO) and supralaryngeal
      characteristics of sustained vowels (F1 and F2 formants, formant bandwidths, two
      dimensional measures of vowel space) and temporal properties of consonant-vowel
      productions (diadochokinetic syllable rates). Perceptual measures were based on
      samples of continuous speech, using the Buffalo voice profile (BVP) and parental
      interviews/questionnaires were used to evaluate other aspects of surgery (i.e.
      subjective speech changes, protracted pain, difficulty swallowing, bleeding,
      etc.). Based on ANOVA, no significant post-surgical changes were detected for the
      majority of acoustic speech measures studied (vocal F0, formant bandwidths,
      measures of vowel space or diadochokinetic rates). However, the F2 formant
      frequency for vowels /i/ and /a/ increased and F1 decreased for /o/ following
      surgery. These changes had the largest effect on the structure of vowel /i/,
      which became more acute and diffuse following surgery. Furthermore, of the
      majority of perceptual measured studied with the BVP, 92% showed no change
      postoperatively. However, in the category of resonance, a significant decrease in
      hyponasality was detected. These results demonstrate that removing soft tissue
      from the oropharynx has only minimal impact on quantitative or qualitative
      (perceptual) aspects of vocal function, when measurements are made approximately
      15 weeks post surgery.

PMID- 10206390
TI  - Suggestion audiometry for non-organic hearing loss (pseudohypoacusis) in
      children.
AB  - Pertaining to non-organic hearing loss in children, three goals should be
      attained: detection of this disease, determination of true hearing levels and
      information about the possible cause. Recently, objective tests have been used
      principally for children with non-organic hearing loss; however, these lack the
      simplicity and convenience of traditional audiometry. A new method, which is
      referred to as suggestion audiometry, since it is suggested to the patient that
      hearing will be improved as a result of the test procedure, was developed for the
      purpose of simultaneously achieving the above-stated three goals. The subjects
      were 20 patients aged 8-16 years suspected of demonstrating non-organic hearing
      loss and whose apparent hearing loss had been identified by school hearing
      examinations. Suggestion pure tone audiometry was useful for the detection of non
      organic hearing loss and suggestion speech audiometry was valuable for the
      determination of true hearing levels. The subjects were classified into four
      groups according to the test results. We discuss causes of the disease based on
      the classification of the subjects obtained from this test procedure.

PMID- 10206391
TI  - Otologic findings in a pediatric cohort with sickle cell disease.
AB  - OBJECTIVE: Sensorineural hearing loss (SNHL) has been associated with sickle cell
      disease (SCD) in older children and adults. Few studies have investigated this
      association in younger children. DESIGN: In a cohort of pediatric patients
      followed at our sickle cell clinic, with a mean age of 7.8 years, 154 audiograms
      were completed on 84 patients. RESULTS: This produced 22 subjects with abnormal
      audiograms. Middle ear effusion was the etiology of 19 subjects' audiometric
      findings. Three children were found to have mild SNHL. None of the subjects had
      hearing loss of severity which would warrant amplification. The prevalence rate
      for SNHL in our cohort of pediatric patients was 3.5%. CONCLUSION: This differs
      from past reports, and may reflect an age dependent prevalence of SNHL in this
      disease.

PMID- 10206392
TI  - Cervical thymic anomalies.
AB  - Because of its infrequent occurrence, cervical thymic tissue is rarely considered
      in the differential diagnosis of neck masses. Consequently, diagnosis is most
      often made by pathologic examination of the excised specimen. The preponderance
      of reported patients have been children and adolescents, typically asymptomatic.
      The clinical presentation, evaluation and surgical management of five new cases
      of cervical thymic anomalies ranging from infancy to adulthood are described. The
      authors also review the embryology and histopathology of these lesions and
      discuss their recommended approach to the evaluation and management of cervical
      thymic anomalies.

PMID- 10206393
TI  - Otoacoustic emission-based hearing screening of a Greek NICU population.
AB  - The pressing need for early identification of hearing-disabled children has led
      to the development of several neonatal hearing screening programmes world-wide.
      Today otoacoustic emissions represent a widely used methodology for
      identification of neonatal hearing impairment. The purpose of the present study
      is to determine the sensitivity and specificity of click-evoked otoacoustic
      emissions (cEOAEs) in a Greek NICU population and compare the cEOAE data to the
      final hearing status of these children. A total of 438 ears of 223 neonates at
      high risk for hearing impairment were tested with both brainstem response
      audiometry (ABR) and cEOAEs. In 107 neonates the final hearing status was
      determined by using behavioural and playtone audiometry, at an age greater than 2
      1/2 years. The sensitivity and specificity of the cEOAEs were found to be 90 and
      92.4% when compared to ABR results and 90.9 and 91.1% when compared to the
      children's hearing status, respectively. Click-EOAEs have been proved to be
      highly effective in determining whether or not hearing impairment really exists.
      Since conventional ABR does not meet the requirements for large scale screening
      programmes, the cEOAEs represent a reliable alternative.

PMID- 10206394
TI  - In vitro inhibition of S. pneumoniae, nontypable H. influenzae and M. catharralis
      by alpha-hemolytic streptococci from healthy children.
AB  - The present study aimed to investigate the inhibitory activity of the normal
      epipharyngeal flora against the three most common acute otitis media (AOM)
      pathogens in healthy children, and to study if the inhibitory activity differs
      between alpha-hemolytic streptococci (AHS) sampled from the tubal orifice and
      from those sampled from the adenoid. A total number of ten isolates of AHS were
      collected from the tubal orifice and the adenoid, respectively, in ten children
      undergoing adenoidectomy or tonsillectomy. None of the children had a history of
      otitis media, neither secretory otitis media (SOM) nor AOM. The method used to
      test the bacterial interference in vitro was a modified agar overlay method. The
      results showed that the AHS from nasopharynx were able to inhibit the majority of
      the S. pneumoniae, nontypable Haemophilus influenzae and Moraxella catharralis
      isolates tested. The AHS isolates from the tubal orifice inhibited growth of 93%
      of S. pneumoniae, 79% of H. influenzae and 84% of M. catharralis isolates. The
      corresponding figures among isolates from the adenoid were 76, 48 and 62%. This
      difference in the inhibitory capacity between the AHS isolates collected from the
      adenoid, compared with the AHS collected from the tubal orifice, is statistically
      significant (P<0.01) and implies that it is important to know the exact sampling
      locality before conclusions are made concerning the significance of bacterial
      interference in the upper airways.

PMID- 10206395
TI  - Analysis of the craniofacial skeleton in cleft children with otitis media with
      effusion.
AB  - Various aspects have been proposed as the cause of otitis media with effusion
      (OME) in cleft lip and/or palate (CL/P) populations (i.e. abnormal anatomic
      relation of Eustachian tube (ET) musculature and soft palate; the lack of intact
      palatal partition; reduction of nasal patency or chronic rhinitis; timing and
      type of surgery). However, the role of deviated craniofacial skeleton (CFS) in
      CL/P has been neglected, although the role of the craniofacial development on
      poor ET function has been advocated in non-cleft children. In this study, we
      evaluated clinical and cephalometric data of 37 Japanese children with unilateral
      complete cleft lip and palate (UCLP, 25) or isolated cleft palate (ICP, 12) and
      compared them to 40 non-cleft children, who were proportionally matched for age
      and sex. Data showed that OME was more often in children with unilateral cleft
      lip and palate-UCLP (76%) and those with isolated cleft palate-ICP (67%) than non
      clefts (10.00%). In addition to a number of skeletal abnormalities (i.e. short
      dimensions related to the posterior cranial base and backward and upward position
      of the maxilla) detected in CL/P cases, mastoid depth and height were also
      shorter in cleft cases than normal subjects. On the other hand, a small tendency
      to recurrent upper airway infection (RUAI) was observed in cleft cases with OME.
      Further, it was found that the following differences in the mastoid-middle ear
      Eustachian tube (M-ME-ET) system were associated with a tendency to OME in UCLP
      cases: more horizontal ET in relation to the posterior cranial base; short bony
      ET; short height and antero-posterior depth of the mastoid air cell system.

PMID- 10206396
TI  - Stuttering children and the probability of remission--the role of cerebral
      dominance and speech production.
AB  - OBJECTIVE: The identification of critical characteristics which might predict
      whether childhood stuttering will become chronic. Part of the study investigates
      the relationship between hearing and central processing of acoustic stimuli,
      cerebral dominance and the clinical course of the stuttering. METHODS: A
      prospective study of 79 stuttering children aged 3-9 years. The subjects were
      examined with regard to their cerebral dominance in various tests of laterality,
      their peripheral hearing and their ability to discriminate sound using the
      dichotic discrimination test according to Uttenweiler (V. Uttenweiler,
      Dichotischer Diskriminationstest fur Kinder, Sprache Stimme Gehor 4 (1980) 107
      111). Results were correlated with the probability of remission of stuttering.
      Comparisons were made with a control group of 18 children of kindergarten age
      with normal speech. The period of investigation was 18 months. RESULTS: Seventy
      two children underwent follow-up examinations. Of these, 36 achieved fluency of
      speech. The results of the dichotic discrimination test showed no relation to the
      rate of remission. When the relationship between handedness and stuttering was
      investigated, it was found that left-handed children had a significantly poorer
      chance of attaining speech fluency. CONCLUSIONS: The Uttenweiler test allowed no
      prognostic evaluation of the future course of stuttering in the age group
      studied, though auditory dominance was not completely developed in a majority of
      the 3-6 year-old children. Handedness, however, appears to be related to the
      probability that stuttering will become chronic.

PMID- 10206397
TI  - Combined rigid and flexible endoscopic removal of a BB foreign body from a
      peripheral bronchus.
AB  - Aspirated foreign bodies (FB) in the peripheral tracheobronchial tree may present
      challenging management problems for the bronchoscopist. Critical to successful
      removal is maintaining airway control while minimizing endoscopy time. An
      innovative approach utilizing rigid and flexible bronchoscopy in removal of a
      distal impacted airway is presented. Difficulties encountered as well as
      advantages of this combined approach are discussed.

PMID- 10206398
TI  - Bifid epiglottis.
AB  - Bifid epiglottis is a rare congenital defect that is often associated with other
      congenital annomalies. The most common defect associated with a bifid epiglottis
      are anomalies of the hands and/or feet (90%) while the most dangerous and
      potentially lethal anomaly if not recognized and treated are hypothalamic
      hamartomas and hypopituitarism (50%). A bifid epiglottis will often result in
      severe respiratory distress secondary to laxity of the cartilage and chronic
      aspirations, which may require surgical intervention. We present the case of a 10
      week-old child who was sent for evaluation of stridor and aspiration. Office
      laryngoscopy demonstrated a true bifid epiglottis and further evaluation
      demonstrated a hypothalamic hamartoma consistent with Pallister-Hall syndrome.
      Management of our case as well as those previously presented in the literature
      are reviewed.

PMID- 10206399
TI  - Epignathus: a germ-cell tumour presenting as neonatal respiratory distress.
AB  - A full-term neonate developed acute upper airway obstruction immediately after
      birth secondary to a polypoidal mass in the oropharynx. After the child's airway
      had been secured, the mass was excised and found to be a nasopharyngeal teratoma,
      a rare congenital germ cell tumour which is frequently associated with other
      congenital malformations. It is sometimes possible to diagnose these tumours in
      utero, thereby enabling appropriate precautions to be taken during the delivery,
      otherwise if the diagnosis is unknown, then it is essential for any attending
      clinician to urgently secure the airway by means of either intubation or
      tracheostomy. Such a case is presented with a review of the possible management
      options. This case emphasises the fact that although many conditions are
      uncommon, the total incidence of rare conditions is surprisingly high, and that
      care needs to be taken at all times in the management of patients, in order not
      to overlook such life-threatening diagnoses.

PMID- 10206400
TI  - Infiltrating lipoma of the head and neck: a report of one pediatric case.
AB  - Infiltrating lipomas are rare benign tumors. Several cases have previously been
      reported in the oral cavity but only three cases have been reported to date in
      children. We report a case of a 7-year-old child with an infiltrating lipoma of
      the neck and a posterior extension to the fourth and fifth cervical roots and the
      vertebral artery. The absence of any neurological signs, negative clinical and
      radiological examination results, as well as, the surgical risk of total removal
      and high rate of recurrence suggested a period of watchful waiting. After 5
      years, the patient's clinical and radiological characteristics remain stable. A
      review of the literature regarding this pathology in the head and neck area, in
      both children and adults is also presented.

PMID- 10206401
TI  - Genetic aspects of (gynecological) tumours.
AB  - In recent years, the genetic aspects of cancer have become important for everyday
      practice in many fields of medicine. Recognition of the hereditary nature of
      'common' cancers in certain families, has shifted the paradigm from 'hereditary
      cancer is extremely rare' to 'any cancer case might be genetic'. Gynecologists,
      therefore, increasingly need to master a number of basic skills and notions from
      clinical genetics: not only in order to adequately appreciate family histories
      and genetic test results, but also to cope with their far-reaching consequences.

PMID- 10206402
TI  - The genetics of endometriosis.
AB  - There is mounting evidence that endometriosis is inherited as a complex trait,
      like diabetes or asthma. This implies there are environmental factors, such as
      dioxin, that are interacting with multiple genetic susceptibility loci to produce
      the phenotype. The Oxford Endometriosis Gene (OXEGENE) study, an international
      collaborative project, seeks to identify the susceptibility loci using linkage
      analysis; the aim then is to use positional cloning techniques to identify genes
      that predispose women to the disease. Analysis of the biochemical function of the
      gene products will lead to a better understanding of the pathophysiology and
      aetiology of endometriosis. New therapies may be designed based upon knowledge of
      the gene function and disease associated genetic markers may be used to identify
      women at high risk of developing the disease.

PMID- 10206403
TI  - Differential gene expression in progesterone-sensitive and progesterone
      insensitive endometrial carcinoma cells.
AB  - High doses of progesterone are used in the treatment of advanced and recurrent
      endometrial cancer. Unfortunately the response rate is relatively low: 10-30%.
      The mechanisms involved in the development of insensitivity to progesterone
      treatment of endometrial cancer tissue are largely unknown. As tumour development
      is thought to be associated with a cascade of genetic alterations, it can be
      expected that genetic changes are involved in the development of progesterone
      insensitivity in endometrial carcinomas. We therefore started an investigation to
      identify, isolate and characterise progesterone-regulated genes involved in
      progesterone-induced growth inhibition in endometrial carcinoma cells. Using
      differential display PCR eight progesterone-regulated cDNA clones were identified
      in endometrial carcinoma cell lines. Four of these progesterone-regulated cDNA
      clones were regulated in the for growth progesterone-sensitive cell line IK-3H12
      and not regulated in the for growth-insensitive cell line ECC-1. This indicates
      that these four cDNA clones represent potentially important genes, which could be
      involved in inhibition of growth of endometrial carcinoma tissue by progesterone.

PMID- 10206404
TI  - The importance of family history in young patients with endometrial cancer.
AB  - Endometrial cancer occurs primarily in postmenopausal women older than 60 years
      of age. Especially in young patients with endometrial cancer, a positive family
      history with respect to cancer and/or development of synchronous or metachronous
      tumors can be indicative of hereditary factors. One genetic disorder, playing an
      important role in the development of endometrial cancer in young women, is
      hereditary non-polyposis colorectal cancer (HNPCC). The mean age to develop
      endometrial cancer because of a mutation in one of the HNPCC-genes is below 50
      years. Mutation carriers have a life-time risk of about 50% for endometrial
      cancer. Especially young patients with endometrial cancer should always be asked
      for the family history and after primary treatment the family history should
      regularly be updated during follow-up.

PMID- 10206405
TI  - Testing for inherited susceptibility to breast and ovarian cancer.

PMID- 10206406
TI  - Genetic alterations in ovarian borderline tumours and ovarian carcinomas.

PMID- 10206407
TI  - Differences between hereditary and sporadic ovarian cancer.
AB  - Approximately 5% of ovarian cancer cases can be attributed to an autosomal
      dominant inheritance factor. The majority of these cases are due to germline
      mutations in the BRCA1 or BRCA2 tumoursupressor genes. Patients with hereditary
      disease do not exhibit pathognomonic features that would allow distinction from
      non-hereditary (sporadic) cases of ovarian cancer. Our studies are aimed at
      identifying clinical, histopathological as well as molecular genetic differences
      between hereditary and sporadic ovarian cancer. Clinical studies of the ovarian
      cancer cases in 31 families revealed differences regarding age at onset and stage
      as well as in survival compared with cancer registry controls. The molecular
      studies of hereditary ovarian cancer are still underway and some preliminary data
      is discussed.

PMID- 10206408
TI  - Is there a place for screening in ovarian cancer?

PMID- 10206409
TI  - Genetic susceptibility testing and prophylactic oophorectomy.
AB  - About 10% of ovarian cancer cases are thought to have a hereditary basis and
      family history is the strongest risk factor for the development of this disease.
      In the past, prophylactic oophorectomy has been advocated for women with two or
      more affected first-degree relatives. More recently, with the identification of
      the genes responsible for most hereditary ovarian cancers (BRCA1, BRCA2),
      oophorectomy can now be offered specifically to women who are mutation carriers.
      Conversely, non-carriers in these families can be reassured that their risk of
      ovarian cancer is not increased. The value of oophorectomy in mutation carriers
      has not yet been proven, however, and there are concerns that the benefit may be
      less than intuitively expected. First, although the lifetime risk of ovarian
      cancer initially was reported to be as high as 60%, more recent studies have
      reported risks in the range of 15-30%. A better understanding of the genetic
      and/or environmental basis of variable penetrance is needed to augment our
      ability to counsel women regarding their risk. In addition, peritoneal papillary
      serous carcinoma indistinguishable from ovarian cancer occurs in some women
      following oophorectomy. Studies that better define how often this occurs also are
      needed to establish more firmly the value of prophylactic oophorectomy. In view
      of the uncertainty regarding the efficacy of prophylactic oophorectomy,
      chemopreventive and early detection approaches also deserve consideration as
      strategies for decreasing ovarian cancer mortality in women who carry mutations
      in ovarian cancer susceptibility genes.

PMID- 10206410
TI  - Genes and gynaecology, who cares?

PMID- 10206411
TI  - Prenatal diagnosis on fetal cells from maternal blood: approaches and
      perspectives.

PMID- 10206412
TI  - Glutathione and glutathione-related enzymes in reproduction. A review.
AB  - Glutathione and glutathione-related enzymes are pivotal for the normal
      functioning of several important biological processes in humans. Glutathione and
      glutathione-related enzymes are involved in the metabolism and detoxification of
      cytotoxic and carcinogenic compounds as well as reactive oxygen species. The role
      of reactive oxygen species in reproduction was the subject of many
      investigations, and there is compelling evidence for the involvement of these
      species in the physiology and pathology of both male and female reproductive
      systems. The glutathione/glutathione-related enzyme system was extensively
      studied in gynaecological oncology, but to a lesser extent in other topics
      related to reproduction. In this paper a review is provided on the
      glutathione/glutathione-related enzyme system in reproduction. Attention is given
      to its role as a detoxicating system, and as an early marker for disease.

PMID- 10206413
TI  - Intrapartum fetal oxygen saturation monitoring in a busy labour ward.
AB  - OBJECTIVE: To measure the ease of use of a fetal pulse oximeter in a busy labour
      ward. DESIGN: Descriptive study in the Labour Ward, National University Hospital,
      Singapore, involving 145 labouring women with singleton pregnancies, and fetuses
      in cephalic presentation, with cervical dilatation >2 cm and amniotic membranes
      ruptured. RESULTS: Placement was comfortable. Oxygen saturation (SpO2) readings
      were obtained in 127 women (87.5%). Adequate readings were obtained a median of
      69% of the time the transducer was in situ. SpO2 values in the last 10 min prior
      to delivery correlated poorly with parameters of neonatal outcome. CONCLUSION:
      The Nellcor N-400 fetal pulse oximeter and FS14 fetal sensor is a feasible method
      of intrapartum fetal monitoring in a busy labour ward and is acceptable to
      labouring women.

PMID- 10206414
TI  - Pregnancy and multiple sclerosis: a 2-year experience.
AB  - OBJECTIVE: To present our experience with management of parturients with multiple
      sclerosis and to examine the role of intravenous immunoglobulin (IVIg) in the
      prevention of postpartum exacerbations of the disease. METHODS: Fifteen patients
      with multiple sclerosis with a relapsing-remitting course were followed during
      pregnancy and 6 months postpartum. To prevent postpartum exacerbations, 14 of the
      patients had received IVIg after delivery. RESULTS: None of the patients who
      received postpartum IVIg relapsed during the 6 months after delivery. None of the
      observed obstetric complications nor the operative deliveries could be related to
      the coexistence of multiple sclerosis. CONCLUSION: Postpartum IVIg treatment is
      beneficial in preventing acute childbirth-associated exacerbations in patients
      with relapsing-remitting multiple sclerosis. Furthermore, this disease does not
      seem to increase obstetric complications.

PMID- 10206415
TI  - The relation between height, foot length, pelvic adequacy and mode of delivery.
AB  - OBJECTIVE: To investigate the value of maternal height and foot length as
      predictors of pelvic adequacy and to evaluate the influence of body components'
      proportions on the mode of delivery. METHODS: Retrospective study of the
      anthropometry of women having normal vertex deliveries (NVD), caesarean sections
      (CS) and vaginal birth after caesarean (VBAC). RESULTS: NVD patients were taller,
      had a longer vertebral column, longer lower limbs and longer feet than CS and
      than VBAC patients. The anthropometric measurements of VBAC patients yielded
      values intermediate between CS and NVD patients. The ratios of height to any of
      the other measured variables (vertebral column, lower limb and foot length) were
      similar in the three groups indicating that the body proportions were the same.
      CONCLUSION: Maternal height and foot length are of limited value as predictors of
      pelvic (in-)adequacy. The anthropometric features of women delivered by CS only
      are similar to those of women having a vaginal birth after Caesarean.

PMID- 10206416
TI  - Maternal serum nitric oxide levels associated with biochemical and clinical
      parameters in hypertension in pregnancy.
AB  - OBJECTIVES: To measure maternal serum concentrations of total nitrites, as an
      index of nitric oxide synthesis, in normal and hypertensive pregnant women, and
      to examine the correlation between these concentrations and several variables of
      clinical interest. STUDY DESIGN: A total of 60 women in four different groups
      were studied: 10 normotensive pregnant women, 17 pregnant women with
      preeclampsia, 18 pregnant women with gestational hypertension and 15 pregnant
      women with chronic hypertension. Serum nitrite levels were determined using the
      Griess reaction after reduction with nitrate reductase. RESULTS: Serum nitrite
      levels were higher in preeclamptic women (34.11+/-14 micromol/l, P=0.04), lower
      in chronic hypertensive women (19.56+/-6.46 micromol/l, P=0.04) and similar in
      women with gestational hypertension (26.97+/-9.44 micromol/l) in comparison to
      the control group (25.37+/-7.24 micromol/l). Serum nitrite levels in preeclamptic
      women had significant positive correlations with hematocrit, fasting insulinemia,
      and apolipoprotein B and negative correlations with platelet count, serum
      phosphorus and glucose:insulin ratio. In pregnant women with chronic hypertension
      a negative correlation was found between serum nitrite levels and active partial
      thromboplastin time. In pregnant women with gestational hypertension, serum
      nitrite levels had negative correlations with birthweight and 24-h urine calcium,
      and positive correlations with mean corspuscular hemoglobin, 24-h urine sodium
      and maternal age. CONCLUSIONS: We suggest that in women with preeclampsia, a
      higher maternal nitric oxide level may act as a compensatory mechanism against
      hemoconcentration and platelet aggregation and that nitric oxide production may
      be related to some metabolic events. In women with gestational hypertension,
      higher serum nitrite levels may be related to clinical and biochemical findings
      common in preeclampsia. In chronic hypertension, a lower maternal nitric oxide
      level is related to the status of coagulation.

PMID- 10206418
TI  - Retroperitoneal mucinous cystadenoma.
AB  - A case of retroperitoneal mucinous cystadenoma histologically confirmed in a 21
      year-old woman is reported. Although ultrasound, CT and MR detected the tumor, a
      preoperative diagnosis could not be established by imaging methods. The cystic
      tumor was removed and microscopic examination revealed a mucinous cystadenoma.
      Mullerian mesothelial metaplasia of peritoneal invagination into the
      retroperitoneal space is the most likely explanation for the histogenesis of
      these tumors.

PMID- 10206417
TI  - Endometriosis: a clinically malignant disease.
AB  - According to the literature this is the first patient with the primary diagnosis
      of an endometriosis (EMT) based on the cardinal symptom of an uremia in
      combination with a colorectal ileus. Operative removal of EMT was possible after
      hormonal suppression with Dienogest.

PMID- 10206420
TI  - The comparison of gonadotropin-releasing hormone agonist therapy and
      intraperitoneal Ringer's lactate solution in prevention of postoperative adhesion
      formation in rat models.
AB  - OBJECTIVE: To evaluate gonadotropin-releasing hormone agonists (GnRH-a) therapy
      and intraperitoneal Ringer's lactate solution (RL) for the prevention of
      postsurgical adhesion formation in rat models. STUDY DESIGN: Forty rats were
      randomized into four groups: Group I was the control; in group II, RL was applied
      at the surgery; group III and IV received preoperative subcutaneous injections of
      the GNRH-a leuprolide acetate and only the diluent of the GNRH-a respectively. A
      standard lesion was created over the uterus of each rat. Adhesions were scored at
      relaparotomy 3 weeks later. Analysis of variance (Kruskal-Wallis) and Mann
      Whitney U-tests were used for the statistical evaluation. RESULTS: The average
      adhesion scores were 2.7+/-0.26, 1.4+/-0.27, 0.9+/-0.18, and 2.5+/-0.34 in groups
      I, II, III, and IV respectively. There were significant differences between the
      scores of groups I and II (P<0.01), groups I and III (P<0.001), groups II and IV
      (P<0.05), and groups III and IV (P<0.01); but not between the scores of groups II
      and III, and groups I and IV (P>0.05). CONCLUSION: GNRH-a was successful in
      reducing postoperative adhesion formation but was not superior to intraperitoneal
      RL.

PMID- 10206419
TI  - Unsuspected extra-adrenal pheochromocytoma simulating ovarian tumor.
AB  - We report on a case of an extraadrenal pheochromocytoma simulating an ovarian
      tumor. Before intervention, the patient exhibited no symptoms suggestive of
      pheochromocytoma. Nevertheless, during surgery she experienced marked blood
      pressure fluctuations, and an unsuspected extraadrenal pheochromocytoma was
      diagnosed. Thus, although rare, when preparing to remove a pelvic mass, the
      gynecologist should consider the possibility of an extraadrenal pheochromocytoma.

PMID- 10206421
TI  - Computer based, temperature controlled bipolar electrocoagulation system. III.
      Effect on pregnancy rate in the rat.
AB  - OBJECTIVE: A computer based, temperature controlled bipolar coagulation system
      has been developed. STUDY DESIGN: Endometriosis was induced in 39 mature female
      rats by means of transplantation of endometrium on the peritoneal wall near the
      ovary. Three weeks later, all the rats were laparotomized and they were
      randomized into five groups according to treatment; an untreated group, a group
      with microsurgical treatment and three groups with electrocoagulation at
      different temperatures (70, 85 and approximately 300 degrees C). Three weeks
      after these treatments they made pregnant after daily examinations of vaginal
      smear. At the ninth day of pregnancy, they were laparotomized again, the number
      of fetus was recorded and the implants were examined for their size and
      histology. RESULTS: In the untreated group, the size of implantation was
      decreased significantly, which suggested a hormone dependent nature for this
      tissue. No further endometriosis was observed in any of the rats treated with
      either microsurgical removal or electrocoagulation at any temperatures examined.
      There was no significant difference in the number of fetus in the treated groups.
      CONCLUSION: Electrocoagulation at a low temperature is as effective as
      microsurgery or electrocoagulation at a high temperature for the treatment of
      endometriosis.

PMID- 10206422
TI  - Recurrent clear cell carcinoma of the ovary changing into producing parathyroid
      hormone-related protein (PTH-rP) with hypercalcemia.
AB  - We experienced the case of a clear cell carcinoma of the ovary arising from an
      endometrial cyst, which started to produce parathyroid hormone-related protein
      (PTH-rP) in a recurrent tumor, thus inducing hypercalcemia. Using
      immunohistochemical analysis, we demonstrated that the primary carcinoma was
      immunonegative for PTH-rP, but that the recurrent carcinoma was strongly
      immunopositive for PTH-rP.

PMID- 10206423
TI  - Silver nitrate for Bartholin gland cysts.
AB  - The management of Bartholin cysts by inserting a silver nitrate stick into the
      cyst cavity was performed in 15 patients. The cyst wall was expelled in 14 (93%)
      with no recurrence in a year. The only complication was the cauterization of the
      surrounding mucosa (20%). This technique seems to offer benefit over conventional
      treatment modalities.

PMID- 10206424
TI  - A six year clinical trial of methotrexate therapy in the treatment of ectopic
      pregnancy [corrected].

PMID- 10206425
TI  - CareWeb, a web-based medical record for an integrated health care delivery
      system.
AB  - With the advent of Integrated Health care Delivery Systems, medical records are
      increasingly distributed across multiple institutions. Timely access to these
      medical records is a critical need for health care providers. The CareWeb project
      provides an architecture for World Wide Web-based retrieval of electronic medical
      records from heterogeneous data sources. Using Health Level 7 (HL7), web
      technologies and readily available software components, we consolidated the
      electronic records of Boston's Beth Israel and Deaconess Hospitals. We report on
      the creation of CareWeb (freya.bidmc.harvard.edu/careweb.htm) and propose it as a
      means to electronically link Integrated Health care Delivery Systems and
      geographically distant information resources.

PMID- 10206427
TI  - Guidelines for using diagnostic imaging devices: an inference system.
AB  - This paper deals with optimising the use of magnetic resonance imaging (MRI)
      scanners through the development of a new kind of clinical guidelines called
      'substrate-specific protocols'. These protocols would link the descriptive
      elements of lesions to the most appropriate imaging techniques on the basis of
      the biophysics of MRI. As many lesions have elements in common, substrate
      specific protocols could have a more general character and be more firmly based
      on evidence than conventional guidelines. We developed an inference model to
      enter, structure and retrieve knowledge acquired through a literature search.
      This proved a practicable and attractive approach. Its exactness, however,
      reveals the imperfections of medical knowledge and clinical practice. We conclude
      that it could be hard to establish an 'evidence basis' for clinical guidelines,
      if 'evidence based' means rooted in natural science.

PMID- 10206426
TI  - A process model of diagnostic reasoning in medicine.
AB  - The paper presents a model-based approach to diagnostic reasoning in medicine. A
      process model is defined on the levels of static elements, dynamic elements and
      reasoning control. Static elements, facts, hypotheses and different types of
      disease knowledge, are identified and variations relevant for hypotheses
      generation are described. Dynamic elements correspond to actions, which in turn
      modify static elements, but are also controlled and started by the expressions of
      the static elements. Hypothesis generation starts with the assessment of a given
      set of facts. According to their priorities, facts are used for the construction
      of a diagnostic differential: new hypotheses are considered, existing hypothesis
      refined or excluded. The purpose of hypotheses generation is to establish a
      complete diagnostic differential with disjunctive explanations which explain a
      given set of facts. The presented model could serve as a basis for an
      implementation in a model-based and process-oriented decision-support system.

PMID- 10206428
TI  - Security in health-care information systems--current trends.
AB  - Ever since health-care information systems have been implemented, their security
      is being considered an important issue, especially in the light of the fact that
      their data are deemed to comprise extremely sensitive information. The prospect
      of storing health information in electronic form raises concerns about patient
      privacy and data security. Any attempt to introduce computerised health-care
      information systems should, therefore, guarantee adequate protection of the
      confidentiality and integrity of patient information. At the same time, the
      patient information also needs to be readily available to all authorised health
      care providers, in order to ensure the proper treatment of the patient. The
      principal aim of the present paper is, however, not to make a new contribution to
      the subject of security per se, but rather to give an overview of current trends
      in the security aspects of health-care information systems. The final section of
      the paper will be devoted to a number of proposals for further research
      possibilities in the domain of health-care information systems security.

PMID- 10206430
TI  - Effect of masoprocol on glucose transport and lipolysis by isolated rat
      adipocytes.
AB  - Masoprocol (nordihydroguaiaretic acid) is a lipoxygenase inhibitor isolated from
      the creosote bush and used by native healers to treat type 2 diabetes. It has
      been recently shown to decrease serum glucose, free fatty acid (FFA), and
      triglyceride (TG) concentrations in rodent models of type 2 diabetes. The current
      study was initiated to quantify the effects of masoprocol incubation of
      adipocytes isolated from normal rats. The results indicate that masoprocol
      significantly increased glucose uptake by adipocytes in both the absence and
      presence of insulin. In addition, the maximal rate of insulin-stimulated glucose
      transport was increased in adipocytes incubated with masoprocol and the insulin
      concentration resulting in a half-maximal glucose transport rate (ED50)
      decreased. Finally, isoproterenol-stimulated increases in FFA and glycerol
      release were significantly decreased in the presence of masoprocol. These results
      provide an explanation at the cellular level for the observation that masoprocol
      decreases serum glucose, insulin, and FFA concentrations in rodent models of type
      2 diabetes.

PMID- 10206429
TI  - Predicting cytomegalovirus disease after renal transplantation: an artificial
      neural network approach.
AB  - Outcome prediction is becoming increasingly important in medicine, but when a
      resource is scarce the need for accurate prediction becomes acute. Prediction
      based on biostatistical models has been in use for many years, but in areas such
      as renal transplantation their results have been disappointing. Recently however,
      there has been growing interest in the use of artificial neural networks for
      prediction. The creation of a large database containing high quality data on
      renal transplantation patients in Wales offers an ideal opportunity to research a
      new area viz., the ability of these techniques to accurately predict outcomes
      such as the appearance of disease in transplant recipients or the time to graft
      failure. This paper describes the use of neural networks to identify patients who
      risk the development of cytomegalovirus disease--a significant cause of mortality
      and morbidity in these patients. The neural networks we examined produced overall
      correct classifications well in excess of 80% in each of the two groups involved,
      diseased and non-diseased. These predictions are a considerable improvement on
      current methods and encourage the belief that renal transplantation data may
      respond well to analysis by neural networks.

PMID- 10206431
TI  - Free cholesterol deposition in the cornea of human apolipoprotein A-II transgenic
      mice with functional lecithin: cholesterol acyltransferase deficiency.
AB  - We have developed several lines of transgenic animals that overexpress different
      levels of human apolipoprotein A-II (apoA-II). The 11.1 transgenic line has human
      apoA-II in plasma at threefold the level in normolipidemic humans and a
      functional lecithin:cholesterol acyltransferase (LCAT) deficiency. The latter is
      a biochemical phenotype similar to that of fish-eye disease (FED), which is
      characterized by free cholesterol (FC) and phospholipid accumulation in the
      cornea, leading to opacity and impaired vision. To assess whether the metabolic
      alterations in these mice also lead to lipid accumulation in the cornea, we fed
      them on a long-term regular chow or high-fat/high-cholesterol (HF/HC) diet. The
      11.1 transgenic mice showed a moderate accumulation of FC in the cornea, but only
      when fed the regular chow diet. This FC accumulation was less severe than the
      accumulation described in FED, which may explain the lack of corneal opacity in
      these mice. Electron microscopy and immunoblotting analysis of the cornea of 11.1
      transgenic mice in comparison to control mice showed (1) a mild but nevertheless
      more intense intracytoplasmatic lipid particle deposition in the epithelial cells
      and (2) a decrease of immunoreactive apoA-I in the area of Bowman's layer and at
      the superficial stroma. The serum capacity to cause cholesterol efflux from rat
      fibroblasts was decreased in 11.1 transgenic mice, but only in those fed a
      regular chow diet. We conclude that 11.1 human apoA-II transgenic mice may be a
      useful model for studies of early lipid deposition in the cornea and its possible
      prevention.

PMID- 10206432
TI  - Regulation of brain glucose transporters by glucose and oxygen deprivation.
AB  - Brain cells are dependent on glucose and oxygen for energy. We investigated the
      effects of hypoxia, glucose deprivation, and hypoxia plus glucose deprivation on
      mRNA and protein levels of glucose transporter (GLUT1) and GLUT3 and 2
      deoxyglucose (2-DG) uptake in primary cultures of rat neurons and astroglia.
      Hypoxia for 24 hours did not significantly affect cell viability but increased
      neuronal GLUT1 and GLUT3 mRNA up to 40-fold and fivefold, respectively, above
      control levels. Similar changes in GLUT1 mRNA were measured in glia. The effects
      of hypoxia on GLUT1 and GLUT3 mRNA were reversible. The increase in GLUT1 mRNA
      could be detected within 20 minutes of hypoxia and was blocked by actinomycin D.
      Nuclear runoff transcription assays showed that hypoxia did not alter the
      transcription rate of GLUT1. However, hypoxia enhanced the stability of GLUT1
      mRNA in neurons (half-life [t(l/2)] > 12 hours) compared with normoxic conditions
      (t(1/2) approximately 10.4 hours), suggesting the existence of a
      posttranscriptional mechanism for the regulation of GLUT1 transcript levels.
      Twenty-four hours of normoxia and 1.0 mmol/L glucose increased neuronal GLUT1
      mRNA less than threefold above basal, but 24 hours of glucose and oxygen
      deprivation increased GLUT1 over 111-fold above basal. Induction of neuronal
      GLUT1 mRNA was temporally associated with increased levels of GLUT1 protein and
      with stimulation of intracellular 2-DG accumulation. We conclude that hypoxia
      reversibly increases the transcript levels of GLUT1 and GLUT3 in rat brain cells
      and stimulates GLUT1 transcript levels by posttranscriptional mechanisms.
      Although glucose deprivation alone produces minimal effects on GLUT mRNA levels,
      hypoxia plus glucose deprivation synergize to markedly increase GLUT gene
      expression.

PMID- 10206433
TI  - Adenosine triphosphate-sensitive potassium channels are involved in insulin
      mediated glucose transport in humans.
AB  - We investigated the influence of treatment with nicorandil, a K-channel opener
      currently used for angina, on glucose homeostasis in patients with non-insulin
      dependent diabetes mellitus (NIDDM) and coronary artery disease (CAD). Adenosine
      triphosphate (ATP)-sensitive K (K-ATP) channels are present in various tissues,
      including pancreatic B cells and skeletal muscle, and are the putative targets of
      this agent. Nine NIDDM patients with CAD and five healthy subjects participated
      in the study. Fasting plasma levels (mean+/-SEM) of glucose (144+/-11 to 180+/-22
      mg/dL, P<.05) and insulin (5.8+/-1.6 to 7.0+/-1.8 microU/mL, P<.05) and
      hemoglobin A1c (7.54+/-0.47 to 8.11+/-0.55%, P<.01) increased significantly in
      nine NIDDM patients after treatment with nicorandil at a dose of 5 mg three times
      daily for 2 to 8 months. Glucose tolerance as examined by an identical meal test
      deteriorated (P<.001), but the insulin response did not change significantly. A
      washout of nicorandil for 1 to 4 months restored glucose tolerance almost to
      pretreatment levels in four patients. A 5- to 7-day trial of nicorandil (5 mg
      three times daily) in five healthy subjects resulted in a marginal to twofold
      increase in fasting plasma insulin, reflecting the progression of insulin
      resistance. In addition, three healthy subjects showed a substantial reduction in
      the glucose infusion rate (GIR) required in the euglycemic-hyperinsulinemic clamp
      study. Since the therapeutic dose of nicorandil did not affect pancreatic B-cell
      function but caused insulin resistance in both healthy and NIDDM subjects, we
      conclude that K-ATP channels play a regulatory role in insulin-mediated glucose
      transport in humans.

PMID- 10206434
TI  - Elevated serum levels of tumor necrosis factor alpha in normal-weight women with
      polycystic ovary syndrome.
AB  - Since an increase in tumor necrosis factor alpha (TNFalpha) expression has been
      associated with insulin resistance, this study was undertaken to determine the
      status of circulating TNFalpha and the relationship of TNFalpha with insulin
      levels, body weight, or both in women with polycystic ovary syndrome (PCOS).
      Fasting serum samples were analyzed in 34 subjects with PCOS, of whom 22 were
      obese (body mass index [BMI]>27 kg/m2), and in 40 normal control women, of whom
      20 were obese. Women with PCOS exhibited a significantly (P<.02) higher mean
      serum TNFalpha concentration compared with the controls. The serum TNFalpha level
      and BMI were directly correlated in women with PCOS (r=.48, P<.005) and highly
      correlated in controls (r=.78, P<.001). When subjects were classified by body
      weight, the mean serum TNFalpha concentration was significantly (P<.001) elevated
      in normal-weight women with PCOS compared with normal-weight controls. On the
      other hand, mean serum TNFalpha concentrations in obese women with PCOS and obese
      controls were similar and significantly (P<.02) higher than in normal-weight
      women with PCOS. A direct correlation between serum fasting insulin and TNFalpha
      was evident in controls (r=.35, P<.03), but not in women with PCOS. However, in
      the subgroup of obese women with PCOS, fasting insulin directly correlated
      (r=.49, P<.03) with TNFalpha and the median fasting serum insulin concentration
      was significantly (P<.05) higher compared with the level in normal-weight women
      with PCOS and all controls. Fasting insulin and TNFalpha were no longer
      correlated in controls as a group and in obese women with PCOS when controlling
      for body weight. Serum TNFalpha did not correlate with luteinizing hormone (LH),
      testosterone (T), or dehydroepiandrosterone sulfate (DHEAS) in women with PCOS.
      However, serum insulin was significantly correlated (r=.49, P<.0004) with T and
      the BMI exhibited a trend for correlation with serum T (r=.33, P=.05) in women
      with PCOS. Finally, the mean serum LH concentration was significantly (P<.02)
      higher in normal-weight women with PCOS versus obese women with PCOS, and serum
      LH levels exhibited a trend for an inverse correlation with the BMI (r=.31,
      P=.09) in women with PCOS. We conclude that (1) serum TNFalpha is increased in
      normal-weight women with PCOS and is even higher in obese individuals regardless
      of whether they have PCOS; (2) factors other than obesity are the cause of
      elevated serum TNFalpha in normal-weight women with PCOS; and (3) whereas
      increased circulating TNFalpha may mediate insulin resistance in obesity, which
      may in turn promote hyperandrogenism in obese women with PCOS, it remains to be
      demonstrated whether this is also the case in normal-weight women with PCOS.

PMID- 10206435
TI  - Nerve conduction and antioxidant levels in experimentally diabetic rats: effects
      of streptozotocin dose and diabetes duration.
AB  - Oxidative stress supposedly plays a role in the pathogenesis of diabetic
      neuropathy. We have studied whether a variation in the streptozotocin (STZ) dose
      or diabetes duration affects the outcome of measurements of oxidative damage in
      relation to nerve conduction. In experiment 1, we induced diabetes in rats using
      40 or 60 mg/kg STZ intravenously and assessed sciatic nerve conduction velocity.
      After 18 weeks, we measured plasma malondialdehyde (MDA) and red blood cell (RBC)
      and nerve glutathione levels. We observed a dose-dependent effect of STZ on body
      weight, and to a lesser extent on nerve conduction, but not on RBC or nerve
      glutathione and plasma MDA. In experiment 2, we administered a fixed dose of STZ
      (40 mg/kg) and measured antioxidants and MDA in RBCs, plasma, and sciatic nerve
      after 2, 4, 8, and 18 weeks in diabetic and control rats. RBC glutathione
      decreased in diabetic animals initially, but did not differ from control values
      after week 4. Plasma total glutathione increased until week 8. The ratio of total
      to oxidized glutathione in the sciatic nerve from diabetic animals paralleled the
      decrease observed in RBCs, and subsequently increased compared with controls.
      Nerve catalase increased in diabetic animals. Endoneurial MDA remained unchanged,
      whereas plasma MDA increased and RBC superoxide dismutase (SOD) decreased in the
      diabetic group. We conclude that differences in antioxidant levels between STZ
      diabetic and control rats depend on the duration of hyperglycemia. Furthermore,
      dose-related effects of STZ on nerve conduction are not reflected in endoneurial
      lipid peroxidation or glutathione.

PMID- 10206436
TI  - Differences in amyloid deposition in islets of transgenic mice expressing human
      islet amyloid polypeptide versus human islets implanted into nude mice.
AB  - Islet amyloid polypeptide (IAPP)-derived amyloid is frequently deposited in the
      islets of Langerhans in patients with chronic non-insulin-dependent diabetes
      mellitus (NIDDM). When human islets were implanted under the renal capsule in
      nude mice, amyloid occurred in 73% of the grafts within 2 weeks. In this study,
      we compare the deposition of amyloid in islets from a transgenic mouse strain
      expressing human IAPP (hIAPP) and in normal human islets after implantation in
      nude mice. The implantations were performed as follows: (1) nondiabetic
      recipients were given islets from transgenic mice alone, (2) human islets were
      implanted in the upper pole of the kidney and islets from transgenic mice were
      implanted in the lower pole of the kidney, (3) grafts containing a mixture of
      human and transgenic islets were implanted, and (4) transgenic islets and islets
      from nontransgenic littermates were implanted in therapeutic numbers into
      recipients made diabetic by a single injection of alloxan prior to implantation.
      The implants were removed after various periods from 4 days to 8 weeks. The
      implants were either fixed in Formalin, stained for amyloid, and viewed in
      polarized light, or processed for immunoelectron microscopy and studied after
      immunolabeling with specific antibodies against IAPP. We found that the course of
      amyloid deposition differed significantly between human islets and hIAPP
      expressing mouse islets. In human islets, amyloid was mainly deposited
      intracellularly and only small amounts of amyloid were found extracellularly. In
      contrast, in islets from transgenic mice, amyloid was exclusively deposited
      extracellularly and deposition in this site was preceded by an aggregation of
      immunoreactive material along the basement membrane. These findings point to
      separate mechanisms for amyloid formation in these two models.

PMID- 10206437
TI  - Effects of dietary fatty acids on lipid metabolism in streptozotocin-induced
      diabetic rats.
AB  - We measured the activity of liver delta9- and delta6-desaturases and examined
      plasma and liver microsome phospholipid fatty acid composition in control and
      diabetic rats fed a basal diet supplemented with 5% (by weight) olive oil (OO),
      sunflower oil (SO), or fish oil (FO), respectively. Plasma glucose, cholesterol,
      triacylglyceride, and phospholipid levels were also measured. An increase in
      plasma and liver microsome oleic acid and a decrease in arachidonic acid were
      found in diabetes. In the liver, docosahexaenoic acid levels were higher in
      diabetic versus control rats. Diabetes increased liver delta9-desaturase in OO
      fed rats and did not modify delta6-desaturase activity in OO- or SO-fed rats.
      Both enzymatic activities were decreased in diabetic rats fed the FO diet. As a
      main conclusion, it appears that diet-induced alterations in membrane composition
      provide a mechanism for improving the diabetic condition in animals and
      overcoming the effect of insulin deficiency on desaturase activities. Plasma
      cholesterol was not modified either by diabetes or by diet. In diabetes, OO-fed
      rats showed the lowest levels of triglycerides. Plasma phospholipids were
      significantly higher in OO-fed versus FO-fed rats. These findings suggest that OO
      contributes to a better control of the hypertriglyceridemia accompanying diabetes
      as compared with the other two diets in this rat model.

PMID- 10206438
TI  - Epinephrine stimulates human muscle lipoprotein lipase activity in vivo.
AB  - Lipoprotein lipase (LPL) is involved in lipoprotein metabolism and nutrient
      partitioning in both adipose tissue and skeletal muscle, and LPL activity is
      regulated by various hormones and the nutritional state. However, the action of
      catecholamines has not been thoroughly investigated in humans. Therefore, the
      effects of exogenous epinephrine on skeletal muscle LPL (SM-LPL) activity and
      whole-body lipid oxidation were studied. Muscle biopsies were obtained from eight
      healthy subjects before, during, and after epinephrine infusion. Somatostatin was
      infused to suppress endogenous insulin production and insulin was infused at a
      constant rate to maintain basal insulin levels throughout the study. After an
      equilibrium period (120 minutes), epinephrine (0.05 microg/kg/min) was infused
      for another 120 minutes. Epinephrine stimulated SM-LPL activity by 21.8%+/-6.8%
      above basal levels from 1.44+/-0.25 to 1.69+/-0.28 micromol free fatty acid
      (FFA)/h/g muscle (P<.02), increased plasma FFA 270% from 0.147 to 0.544 mmol/L
      (P<.05), and increased lipid oxidation 45% from 4.37 to 6.36 mg/kg/min (P<.05).
      The increase in SM-LPL activity was positively correlated with the increase in
      whole-body lipid oxidation (R=.75, P<.05). Finally, lipid oxidation and SM-LPL
      activity were negatively correlated with whole-body glucose oxidation. Overall,
      the results demonstrate that epinephrine is able to stimulate SM-LPL activity in
      humans, and thus may have opposite effects on adipose tissue and SM-LPL activity.

PMID- 10206439
TI  - Exogenous hyperinsulinemia causes insulin resistance, hyperendothelinemia, and
      subsequent hypertension in rats.
AB  - In many clinical and animal studies, hypertension and insulin resistance coexist,
      but their mechanistic relationship is unclear. We explored the causal link
      between these two parameters in a rat model with chronic hyperinsulinemia induced
      with human insulin (1 U/d) released from subcutaneously implanted minipumps. Rats
      with saline minipumps served as a control. During the first experiment, plasma
      levels of insulin and glucose and the systolic blood pressure of the two groups
      were continuously monitored for 17 days. In the subsequent four experiments, rats
      were killed on days 10 and 13 to measure plasma endothelin-1 (ET-1) levels and
      the glucose transport into and insulin and ET-1 binding of isolated adipocytes.
      In one experiment, rats were tested for oral glucose tolerance on days 10 and 13.
      In another experiment, ET-1 binding to the aortic plasma membrane was also
      determined. The results showed that rats became hyperinsulinemic throughout the
      experimental period by the instillation of exogenous insulin. Hyperinsulinemic
      rats were consistently hypoglycemic during the first day, but they became
      euglycemic thereafter, indicating an insulin-resistant state. Glucose intolerance
      was obvious by day 10, but significant hypertension was not detected until the
      11th day on insulin infusion. Compared with the saline controls, insulin-infused
      rats had an increase of plasma ET-1 levels but a decrease of both basal and
      insulin-stimulated glucose transport into adipocytes. ET-1 binding to adipocytes
      of the insulin-infused group was elevated significantly from day 10 through day
      13. ET-1 binding to the aortic membranes, supposedly downregulated by the
      increased plasma ET-1 and hypertension, was similar to that found in the controls
      on day 13. These results imply that hyperinsulinemia in rats could lead to
      hypertension via the elevation of plasma ET-1 levels together with an unaltered
      vascular binding of ET-1, which was probably unrelated to the insulin resistance.

PMID- 10206440
TI  - Effects of hypoosmolality on whole-body lipolysis in man.
AB  - Changes in extracellular osmolality, and thus in the cellular hydration state,
      appear to directly influence cell metabolism. The metabolic changes associated
      with cell swelling are inhibition of glycogenolysis, glycolysis, and proteolysis.
      Recent studies in our laboratory demonstrated diminished whole-body protein
      breakdown in humans during an acute hypoosmolar state. Because of the close
      interrelationship between carbohydrate and fat metabolism, we speculated that
      adipose tissue lipolysis and fatty acid oxidation are regulated by changes in
      extracellular osmolality. Therefore, we investigated the effect of artificially
      induced hypoosmolality on whole-body lipolysis and fat oxidation in seven healthy
      young men. Hypoosmolality was induced by intravenous administration of
      desmopressin, liberal ingestion of water, and infusion of hypotonic (0.45%)
      saline solution. Lipolysis was assessed by a stable-isotope method (2-[13C]
      glycerol infusion). The glycerol rate of appearance (Ra), reflecting whole-body
      lipolysis, was higher under hypoosmolar compared with isoosmolar conditions
      (2.35+/-0.40 v 1.68+/-0.21 micromol/kg/min, P=.03). This was even more pronounced
      when lipolysis was suppressed during hyperinsulinemia and euglycemic clamping
      (0.90+/-0.08 v 0.61+/-0.03 micromol/kg/min, P=.002). However, plasma free fatty
      acid (FFA), glycerol, ketone body, insulin, and glucagon concentrations and
      carbohydrate and lipid oxidation measured by indirect calorimetry were not
      significantly altered by hypoosmolality. Plasma norepinephrine concentrations
      were lower under hypoosmolar conditions (P<.01 v control). In conclusion,
      hypoosmolality in vivo results in increased whole-body lipolysis, which is not
      due to changes in major lipolysis regulating hormones.

PMID- 10206441
TI  - Changes in islet capillary angioarchitecture coincide with impaired B-cell
      function but not with insulin resistance in male Otsuka-Long-Evans-Tokushima
      fatty rats: dimorphism of the diabetic phenotype at an advanced age.
AB  - The Otsuka-Long-Evans-Tokushima fatty (OLETF) rat is a genetic model of
      spontaneous development of non-insulin-dependent diabetes mellitus (NIDDM)
      established as an inbred strain after 20 generations of selective breeding.
      Although they are thought to be genetically homogeneous, they show a dimorphism
      regarding the diabetic phenotype at an advanced age, with one remaining obese and
      modestly diabetic while the other becomes lean and overtly diabetic. To clarify
      the causes for this divergence, we examined the physical, biochemical, and
      histopathological features in rats at 50 weeks of age, including an analysis of
      islet angioarchitecture. Sixty-one of 85 male OLETF rats lost weight, while the
      remainder remained obese. Mean nonfasting plasma glucose in the lean group was
      21.8+/-4.6 mmol/L, significantly higher versus the obese group (10.5+/-1.4
      mmol/L) and the age-matched control Long-Evans-Tokushima-Otsuka (LETO) group
      (7.1+/-0.6 mmol/L). Morphological studies of the pancreas from the lean group
      showed enlarged multilobulated fibrotic islets with a paucity of B cells, whereas
      islets from the obese group appeared slightly enlarged and showed a relative
      abundance of B cells. The fine capillaries that form a network in the islets were
      extremely sparse in the lean group, resulting in a defective glomerular-like
      configuration, whereas those from the obese group were dense, forming a nearly
      typical glomerular-like configuration. Increased plasma insulin responses to oral
      and intravenous (i.v.) glucose and i.v. glucagon loads were nearly absent in the
      lean group, while they were evident in the obese group, although to a lesser
      extent compared with the LETO group. Mean insulin secretory output from the
      perfused pancreas in response to 11.1 mmol/L glucose in the lean group (3.5+/-2.2
      pmol/20 min) was significantly lower versus the obese group (8.8+/-6.5 pmol/20
      min) and LETO group (22.0+/-10.8 pmol/20 min). Similarly, pancreatic insulin
      content was significantly lower in the lean group (9.3+/-6.1 microg) versus the
      others (26.1+/-17.3 microg for obese and 41.1+/-24.8 microg for LETO). In vivo
      insulin-stimulated glucose uptake measured by a euglycemic clamp technique was
      significantly higher in the lean group compared with the obese group. These
      results demonstrate that the dimorphism regarding the diabetic phenotype in male
      OLETF rats at 50 weeks of age was due to differences in the number of islet B
      cells, which could be the result of a variation in the capacity for B-cell
      proliferation among male OLETF rats.

PMID- 10206442
TI  - Altered purine and glycogen metabolism in skeletal muscle during exercise in
      patients with heart failure.
AB  - Plasma levels of ammonia and hypoxanthine (HX) can be indices of purine
      nucleotide degradation. The present study determined if patients with heart
      failure (HF) have altered exercise plasma ammonia and HX levels relative to the
      peak work rate performed. Blood lactate, plasma ammonia, and plasma HX levels
      were measured in 59 patients with HF (New York Heart Association [NYHA] classes
      I:20, II:21, and III:18) and 21 controls at rest and after a maximal
      cardiopulmonary exercise test. The peak work rate (normal and NYHA I, II, and
      III, 163+/-11, 152+/-9, 94+/-5, and 69+/-5 W) and peak oxygen uptake ([VO2]
      32.3+/-1.7, 25.1+/-0.9, 18.6+/-0.5, and 14.1+/-0.6 mL/min/kg) decreased as the
      NYHA functional class increased. The increment from rest to peak exercise (delta)
      for lactate ([(delta)lactate] 6.1+/-0.3, 4.8+/-0.4, 4.6+/-0.3, and 2.9+/-0.3
      mmol/L), (delta)ammonia (132+/-14, 119+/-20, 94+/-13, and 32+/-6 microg/dL), and
      (delta)HX (33.5+/-3.4, 24.9+/-4.7, 20.6+/-3.0, and 9.9+/-1.2 micromol/L) was
      progressively smaller as HF worsened. The ratio for (delta)lactate to peak work
      rate (0.037+/-0.003, 0.032+/-0.004, 0.049+/-0.003, and 0.042+/-0.005) was higher
      in classes II to III HF, while the ratio for (delta)ammonia to peak work rate
      (0.81+/-0.14, 0.78+/-0.16, 0.99+/-0.11, and 0.47+/-0.11) was significantly lower
      in class III HF. In summary, patients with HF exhibited a smaller ammonia
      response with a higher lactate response to exercise when normalized with the peak
      work rate. These results suggest there may be an altered purine and glycogen
      metabolism during exercise in skeletal muscle in patients with HF.

PMID- 10206443
TI  - Effects of soybean protein and very low dietary cholesterol on serum lipids,
      biliary lipids, and fecal sterols in humans.
AB  - Soy-base texturized vegetable protein (TVP; Archer Daniels Midland, Decatur, IL)
      has been used to decrease serum cholesterol and as a substitute for animal
      protein to achieve very low levels of dietary cholesterol. The effect of very low
      dietary cholesterol and of TVP on biliary lipids and fecal sterols is unclear.
      The study objective was to determine the effects of very low intake of dietary
      cholesterol, as well as TVP itself, on serum lipids, biliary lipids, and fecal
      sterols. We studied eight normal subjects living on a metabolic ward during three
      randomly ordered 6- to 7-week periods: (1) standard cholesterol diet (190 to 550
      mg/d), (2) TVP-low-cholesterol diet (17 to 30 mg/d), and (3) TVP-standard
      cholesterol diet. By analysis of covariance (ANCOVA), reducing dietary
      cholesterol to these very low levels significantly decreased serum low-density
      lipoprotein (LDL) cholesterol (P=.048) but did not affect high-density
      lipoprotein (HDL) cholesterol or triglyceride. TVP resulted in a borderline
      significant reduction in LDL cholesterol (P=.058) with a highly significant
      reduction in HDL cholesterol (P=.004) and an increase in serum triglyceride
      (P=.010). During TVP ingestion, there was a highly significant increase in the
      output of fecal neutral sterols (P=.005) and a tendency for a higher output of
      fecal acidic sterols (P=.100). Fecal sterol balance was significantly more
      negative (indicating increased cholesterol synthesis) during TVP ingestion
      (P=.016). Neither TVP nor the very-low-cholesterol diet appreciably affected the
      gallbladder bile molar percent cholesterol or saturation index. The data are
      consistent with the hypothesis that to the extent TVP decreases serum LDL
      cholesterol (an effect of borderline significance in this study), the effect
      occurs via a reduction in the absorption of cholesterol and perhaps bile acid.
      However, the potential benefit of decreasing LDL cholesterol in this way seems to
      be at least partially offset by a concomitant reduction in HDL cholesterol and an
      increase in serum triglycerides.

PMID- 10206445
TI  - Changes in thyroid function tests during short-term salsalate use.
AB  - Although long-term administration of salsalate depresses blood levels of both
      total thyroxine (T4) and total triiodothyronine (T3) and at least transiently
      decreases serum thyrotropin (TSH), changes in thyroid function tests have not
      been fully characterized during its short-term use. It is also unclear if the
      observed changes are solely the result of decreased hormone binding to carrier
      proteins or if reduced hepatic 5'-monodeiodinase activity is important. Blood was
      sampled at baseline (day 0) and after 24 hours (day 1) and 72 hours (day 3) in
      eight subjects taking a therapeutic dose of salsalate 1,500 mg twice daily. Total
      T4 decreased from 90.1+/-7.7 nmol/L (mean+/-SD) on day 0 to 82.9+/-8.6 nmol/L on
      day 1 (P=.1 v baseline) and 68.6+/-8.7 nmol/L on day 3 (P=.0001). Total T3
      decreased from 1.76+/-0.20 nmol/L to 1.61+/-0.16 nmol/L on day 1 (P<.05) and
      1.31+/-0.27 nmol/L on day 3 (P=.002). The T4/T3 ratio was 51.7+/-7.7 at baseline
      and remained unchanged after 3 days. Levels of reverse T3 (rT3) were reduced from
      0.24+/-0.05 nmol/L to 0.18+/-0.02 nmol/L on day 3 (P<.05). While the free T4
      index (FTI) declined in parallel with total T4, the free T4 level by direct
      equilibrium dialysis (FTD) was unchanged after 3 days. Serum TSH decreased from
      1.47+/-0.47 mU/L to 0.91+/-0.27 mU/L after 1 day (P<.05) and remained suppressed
      after 3 days (0.95+/-0.49 mU/L, P<.05). In conclusion, (1) therapeutic doses of
      salsalate significantly decrease serum concentrations of total T4, total T3, and
      rT3 to about 75% of baseline levels after 3 days without altering the T4/T3
      ratio; (2) although the FTD does not change, serum TSH concentrations remain
      suppressed; and (3) the proportionate decrease in total thyroid hormone levels
      suggests that inhibition of hormone binding to serum proteins is more important
      in producing these changes than reduced hepatic 5'-monodeiodinase activity.

PMID- 10206444
TI  - Acute effects of adrenergic-mediated ischemia on nerve conduction in subjects
      with type 2 diabetes.
AB  - Several lines of evidence support peripheral nerve ischemia as a contributing
      factor in the etiology of human diabetic neuropathy. We questioned whether
      diabetic subjects with relatively normal nerve function in the baseline state
      would be more likely than healthy control subjects to show either improvement of
      ulnar nerve function with acute intraarterial infusion of nitroprusside
      (vasodilation) or be more sensitive than control subjects to worsening of nerve
      function with acute intraarterial infusion of norepinephrine (vasoconstriction).
      We measured forearm blood flow (FABF) using venous occlusion plethysmography and
      assessed ulnar nerve function at baseline and during two intrabrachial artery
      infusions. Six nondiabetic control subjects (mean age, 56 years) and 11 subjects
      with type 2 diabetes (mean age, 58 years) in good general health participated.
      Only three type 2 diabetic subjects had peripheral sensory neuropathy, which was
      mild. Among control subjects, there was no significant change in sensory distal
      latency, motor distal latency, motor proximal latency, or sensory or motor
      conduction velocity during norepinephrine infusion. In contrast, among type 2
      diabetic subjects, there was a significant increase in sensory (baseline
      vnorepinephrine, 2.73+/-0.10 v 2.94+/-0.10 milliseconds [MS], P< or =.01) and
      motor distal latencies (baseline v norepinephrine, 2.90+/-0.06 v 3.18+/-0.1 ms,
      P< or =.001) and motor proximal latency (baseline v norepinephrine, 7.15+/-0.18 v
      7.60+/-0.23 ms, P<.01) and a decrease in sensory conduction velocity (baseline v
      norepinephrine, 52.1+/-2.0 v 47.7+/-1.6 m/s, P<.01) during norepinephrine
      infusion. There were no consistent changes in nerve function during nitroprusside
      infusion in either group. In summary, we found that subjects with type 2
      diabetes, but not control subjects, demonstrate a decrement in nerve function
      with vasoconstriction during intraarterial infusion of norepinephrine, but no
      consistent change during nitroprusside-induced vasodilation. These findings
      suggest there may be enhanced sensitivity of nerve function to ischemia in type 2
      diabetic subjects with mild or absent clinical neuropathy.

PMID- 10206446
TI  - Lipoic acid acutely induces hypoglycemia in fasting nondiabetic and diabetic
      rats.
AB  - Lipoic acid (LA) is a unique antioxidant that increases peripheral glucose
      utilization in diabetic patients. This study was conducted to investigate whether
      the inhibition of glucose production could be an additional mechanism for the
      action of LA. Intravenous (i.v.) LA injection (100 or 60 mg/kg body weight) to
      fasting nondiabetic or streptozotocin (STZ)-induced diabetic rats caused a rapid
      reduction in blood glucose with no effect on circulating insulin levels. In vivo
      conversion of fructose to glucose was not inhibited by LA, whereas the
      gluconeogenesis flux from alanine was completely prevented. Reduced liver
      pyruvate carboxylase (PC) activity in vivo is suggested by the finding that LA
      induced a decrease in liver coenzyme A (CoA) content (44% and 28% reduction in
      nondiabetic and diabetic rats, respectively, compared with vehicle-treated
      animals) and liver acetyl CoA content (80% and 67% reduction in nondiabetic and
      diabetic rats, respectively). A reduction in plasma free carnitine (42% and 22%
      in nondiabetic and diabetic rats, respectively) was observed in LA-treated
      animals, and acylcarnitine levels were increased twofold. This could be
      attributed to elevated levels of C16 and C18 acylcarnitine, without a detectable
      accumulation of lipoylcarnitine. Under such conditions, a significant increase in
      the plasma free fatty acid (FFA) concentration (204% in nondiabetic and 151% in
      diabetic animals) with no elevation in beta-hydroxybutyrate levels was noted. In
      conclusion, this study suggests that short-term administration of LA at high
      dosage to normal and diabetic rats causes an inhibition of gluconeogenesis
      secondary to an interference with hepatic fatty acid oxidation. This may render
      LA an antihyperglycemic agent for the treatment of diabetic subjects, who display
      glucose overproduction as a major metabolic abnormality.

PMID- 10206447
TI  - Metformin-induced resumption of normal menses in 39 of 43 (91%) previously
      amenorrheic women with the polycystic ovary syndrome.
AB  - In 43 amenorrheic women with polycystic ovary syndrome (PCOS), 31 (74%) with
      fasting hyperinsulinemia (> or =20 microU/mL), our aim was to determine whether
      Metformin (Bristol-Myers Squibb, Princeton, NJ), which reduces hyperinsulinemia,
      would reverse the endocrinopathy of PCOS, allowing resumption of regular normal
      menses. A second aim was to assess the effects of weight loss versus other
      Metformin-induced effects on ovarian function, and to determine if there were
      different responses to Metformin between those who lost weight and those who did
      not. A third aim was to assess associations between PCOS, 4G/5G polymorphism in
      the promoter sequence of the plasminogen activator inhibitor-1 gene (PAI-1 gene),
      and PAI activity (PAI-Fx). Of the 43 women, 40 (93%) had normal fasting blood
      glucose and 37 had normal hemoglobin A1C (HgA1C); onlythree (7%) had type 2
      diabetes mellitus. Metformin (1.5 to 2.25 g/d) was given for 6.1+/-5.1 months
      (range, 1.5 to 24), to 16 patients for less than 3 months, to 12 for 3 to 6
      months, and to 15 for at least 6 months. On Metformin, 39 of 43 patients (91%)
      resumed normal menses. The percentage of women resuming normal menses did not
      differ among treatment duration groups (P<.1) or among dose groups (P>.1). The
      body mass index (BMI) decreased from 36.4 + 7 Kg/m2 at study entry to 35.1+/-6.7
      on Metformin (P=.0008). Of 43 patients, 28 (67%) lost weight (1 to 69 pounds),
      with nine (21%) losing at least 12 pounds. On Metformin, the median fasting serum
      insulin decreased from 26 microU/mL to 22 (P=.019), testosterone decreased from
      61 ng/dL to 47 (P=.003), and estradiol increased from 41 pg/mL to 71 (P=.0001).
      Metformin-induced improvements in ovarian function were independent of weight
      loss (testosterone decrease, P<.002; estradiol increase, P<.0004). The change in
      response variables on Metformin did not differ (P>.05) between those who lost
      weight and those who did not, excepting Lp(a), which increased 4 mg/dL in those
      who lost weight and decreased 9 mg/dL in those who did not (P = .003). The change
      in response variables on Metformin did not differ among the five quintiles of
      weight loss, excepting fasting glucose (P<.05), which increased 6 mg/dL in those
      who lost the least weight on Metformin versus those in the 60th to 80th
      percentile for weight loss, in whom glucose decreased 33 mg/dL. Although the
      pretreatment fasting serum insulin was not significantly correlated with
      testosterone (r=.24, P=.13) or androstenedione (r=.27, P=.09), on Metformin, the
      change in insulin correlated positively with the change in testosterone (r=.35,
      P=.047) and with the change in androstenedione (r=.48, P=.01). Patients were more
      likely than normal controls (83% v 64%, P=.016) to be heterozygous or homozygous
      for 4G polymorphism of the PAI-1 gene and were also more likely to have high PAI
      Fx (> or =22 U/mL, 28% v3%, chi(2)=10.1, P=.001). Metformin reduces the
      endocrinopathy of PCOS, allowing resumption of normal menses in most (91%)
      previously amenorrheic women with PCOS.

PMID- 10206448
TI  - Effects of fructose and xylitol on the urinary excretion of adenosine, uridine,
      and purine bases.
AB  - To examine whether fructose and xylitol increase the plasma concentration and
      urinary excretion of adenosine, as well as uridine and purine bases
      (hypoxanthine, xanthine, and uric acid), we intravenously administered xylitol
      and, 2 weeks later, fructose, to five healthy subjects. Analyses of blood and
      urine samples obtained during these infusion studies demonstrated that fructose
      increased the urinary excretion of adenosine and uridine 11.9- and 105.5-fold,
      respectively, and caused only a small increase in the plasma concentrations of
      uridine and purine bases. It was further demonstrated that xylitol increased the
      urinary excretion of uridine 58.4-fold, with a marked increase in the plasma
      concentrations of purine bases and uridine but without an increase in the urinary
      excretion of adenosine. However, neither infusion increased the plasma
      concentration of adenosine. These results suggest that in addition to many
      organs, including the liver, fructose is significantly metabolized by an abrupt
      adenosine triphosphate (ATP) consumption in the kidney, leading to an increase in
      the urinary excretion of adenosine and uridine. They also suggest that xylitol is
      not significantly metabolized in the kidney.

PMID- 10206449
TI  - Growth hormone (GH) response to GH-releasing peptide-6 and GH-releasing hormone
      in normal-weight and overweight patients with non-insulin-dependent diabetes
      mellitus.
AB  - The growth hormone (GH) response to GH-releasing hormone (GHRH) in patients with
      non-insulin-dependent diabetes mellitus (NIDDM) was found to be either decreased
      or normal. The recent introduction of a new and potent GH stimulus, GH-releasing
      peptide-6 (GHRP-6), allowed further investigation of the functional properties of
      somatotropes in a variety of metabolic diseases. The aim of the present study was
      to investigate the response of GH to GHRP-6, GHRH, and GHRP-6 + GHRH in NIDDM
      patients. Twenty-one patients with NIDDM were divided into two groups: group A,
      normal weight (body mass index [BMI], 23.31+/-0.62 kg/m2); and group B,
      overweight (BMI, 27.62+/-0.72 kg/m2). Eight normal-weight control subjects (group
      C) were studied. Each subject received GHRP-6 (90 microg intravenously [i.v.]),
      GHRH (100 microg i.v.), and GHRP-6 + GHRH on three separate occasions. There was
      no difference between the GH response after GHRP-6 in groups A, B, and C in terms
      of the GH peak (50.95+/-11.55, 51.96+/-7.71, and 70.07+/-15.59 mU/L, P>.05) and
      the area under the curve (AUC) for GH (2,340.06+/-617.36, 2,684.54+/-560.57,
      3,462.78+/-1,223.53 mU/L/120 min, P>.05). A decreased GH response to GHRH was
      found in group B in comparison to group A (B v A: peak GH response, 8.25+/-1.90 v
      22.19+/-8.81, P<.05; AUC GH, 479.62+/-84.0 v 1,443.21+/-743.76, P<.05). There was
      no difference in the GH response between group A and group C (peak GH response,
      22.19+/-8.81 v 26.42+/-6.71, P>.05; AUC, 1,443.21+/-743.76 v 1,476.51+/-386.56,
      P>.05). There was a significant difference between the same parameters in group B
      versus group C (8.25+/-1.90 v 26.42+/-6.71, P<.05; AUC, 479.62+/-84.0 v
      1,476.51+/-386.56, P<.05). The combined administration of GHRP-6 + GHRH elicited
      a synergistic GH response in NIDDM patients and controls. There was a significant
      difference between groups A and B for the GH peak (96.49+/-9.80 v 68.38+/-8.25,
      P<.05), whereas there was no difference for the AUC (5,111.13+/-703.77 v
      3,425.95+/-459.67, P>.05). There was no difference in the peak GH after the
      combined test between group A and group C (96.49+/-9.80 v 139.82+/-24.16, P>.05),
      whereas the peak GH in the same test was significantly decreased in group B in
      comparison to group C (68.38+/-8.25 v 139.82+/-24.16, P<.05). The AUC for GH
      after combined GHRP-6 + GHRH in group A versus group C was not significantly
      different (5,111.13+/-703.77 v 9,274.71+/-1,541.46, P>.05), whereas there was a
      significant difference for the same test between group B and group C (3,425.95+/
      459.67 v 9,274.71+/-1,541.46, P<.05). Our results demonstrate that normal-weight
      NIDDM patients have a preserved GH response to GHRP-6, GHRH, and GHRP-6 + GHRH,
      and overweight NIDDM patients have a blunted response to GHRH and GHRP-6 + GHRH.
      The preserved GH response to GHRP-6 in both diabetic groups suggests that the
      secretory potential of somatotropes is preserved in NIDDM patients. The
      impairment of the GH response to GHRH in overweight NIDDM patients could be a
      functional defect due to the obesity, since it could be overridden by
      administration of GHRP-6.

PMID- 10206450
TI  - Low-density lipoprotein particle size and coronary artery disease in a childhood
      onset type 1 diabetes population.
AB  - Low-density lipoprotein (LDL) cholesterol has been widely recognized as a strong
      predictor of coronary artery disease (CAD). Recently, studies have examined the
      influence of LDL particle size (an integral part of the insulin resistance
      syndrome) on the development of CAD in the general population. This report
      examines the correlates of LDL particle size and its association with CAD in a
      type 1 diabetes population. We evaluated the interrelationships between LDL
      particle size and the presence of CAD in a cohort of childhood-onset type 1
      diabetic subjects using the Pittsburgh Epidemiology of Diabetes Complications
      (EDC) study. LDL particle size was measured in 337 subjects (mean age, 35.6
      years; mean diabetes duration, 27.2 years) who underwent the 8-year follow-up
      examination. LDL particle size was determined by vertical polyacrylamide gel (2%
      to 16%) electrophoresis. Subjects with the small dense LDL particle phenotype
      (<235.5 angstroms) [corrected] had a longer diabetes duration, higher
      cholesterol, triglyceride, LDL, fibrinogen, waist to hip ratio (WHR), and
      hemoglobin A1 (HbA1), and lower high-density lipoprotein (HDL) cholesterol
      compared with subjects with the large LDL particle phenotype (>257 angstroms)
      [corrected]. Males were also more likely to have an increased body mass index
      (BMI) and CAD, while females were more likely to have hypertension and a family
      history of type 2 diabetes (a potential marker of insulin resistance and CAD
      risk). The odds ratio ([OR] 95% confidence, interval [CI]) using logistic
      regression analysis for LDL particle size in association with CAD was 0.79 (0.60
      to 1.04). Multivariate modeling indicated that the duration of type 1 diabetes,
      depressive symptomatology, and triglycerides were independently associated with
      the presence of CAD. We conclude that although small dense LDL particle size is
      associated with CAD in our type 1 diabetes population, its borderline association
      can largely be explained by the triglyceride concentration. However, as in the
      general population, LDL particle size is associated with many elements of the
      insulin resistance syndrome, including a family history of type 2 diabetes, and
      is likely an important element in the contribution of insulin resistance to the
      development of CAD in type 1 diabetes.

PMID- 10206451
TI  - Age-related differences in corticosterone secretion in female rats.
AB  - The effects of age on steroidogenesis in rat zona fasciculata-reticularis (ZFR)
      cells were studied. Young, adult, and middle-aged rats were ovariectomized (Ovx)
      and received replacement therapy with oil or estradiol benzoate ([EB] 25
      microg/mL/kg). Rat ZFR cells were incubated with corticotropin (ACTH), prolactin
      (PRL), or forskolin at 37 degrees C for 1 hour. The effects of age on the
      activity of steroidogenic enzymes of ZFR cells were measured by the amount of
      intermediate steroidal products separated by thin-layer chromatography. Plasma
      levels were higher for PRL (54% to 254%) and corticosterone (179% to 257%) in
      middle-aged versus young rats. In oil-treated Ovx rats, basal and ACTH-stimulated
      corticosterone release by ZFR cells were also greater in middle-aged compared
      with young rats. Replacement with EB in Ovx rats increased the ACTH-stimulated
      release of corticosterone. Administration of ovine PRL in vitro resulted in a
      dose-dependent increase of corticosterone production. In oil-treated middle-aged
      rats, ovine PRL-stimulated corticosterone release was higher than in young rats.
      Forskolin-induced production of cyclic adenosine 3',5'-monophosphate (cAMP) was
      greater in middle-aged versus young rats and correlated with the increase of
      corticosterone production. The activity of steroidogenic enzymes in rat ZFR cells
      was unchanged by age. These results suggest that the age-related increase of
      corticosterone production in female rats is associated with the stimulatory
      effect of PRL on ZFR cells and is due in part to an increase of cAMP generation.

PMID- 10206452
TI  - Modern trends in non-Hodgkin lymphoma.

PMID- 10206453
TI  - Whenever possible, use the gut!

PMID- 10206454
TI  - Chromosomal rearrangements in childhood acute myeloid leukemia and
      myelodysplastic syndromes.
AB  - Recurrent chromosomal abnormalities present in the malignant cells of children
      with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) often
      correlate closely with specific clinical and biologic characteristics of the
      disease. Certain unique cytogenetic rearrangements are associated with distinct
      morphologic leukemic subtypes. These rearrangements should be detectable in most
      children with AML and MDS with the use of complementary molecular techniques such
      as fluorescence in situ hybridization (FISH), Southern blotting, and polymerase
      chain reaction. Apart from the diagnostic assessment, cytogenetic findings
      sometimes predict clinical outcome and thus also serve as prognostic parameters,
      which may affect the therapeutic decision. Alternative classifications of AML
      that take into account the genetic information are being proposed. Cytogenetic
      and molecular analyses may allow clinicians to more appropriately direct types of
      treatment. Abnormal fusion transcripts and chimeric proteins derived from
      karyotypic abnormalities now are being also targeted by novel therapeutic
      approaches.

PMID- 10206455
TI  - Non-Hodgkin lymphoma in children: a 20-year population-based epidemiologic study
      in western Sweden.
AB  - PURPOSE: The aim of this study was to investigate incidence, clinicopathologic
      features, prognostic risk factors, and long-term survival in non-Hodgkin lymphoma
      (NHL) in a 20-year population-based study of children using Swedish health care
      organizations and their central registry for childhood malignancies. PATIENTS AND
      METHODS: The hospital registry, the Cause of Death Registry, and the two
      established Swedish registries for malignancy (the Swedish Cancer Registry and
      the National Registry for Solid Tumours in Childhood) were searched for children
      in western Sweden with NHL diagnosed from 1975 to 1994. The clinical files of all
      children with NHL were collected and abstracted for information regarding age at
      diagnosis, gender, disease characteristics, treatment, and outcome of treatment.
      All sections from paraffin-embedded blocks of tumors with a diagnosis of
      malignant lymphoma were collected and reexamined histopathologically and
      immunohistochemically. To guarantee that no patients with NHL were misdiagnosed,
      a reexamination of other childhood malignancies collected from these registries
      was also performed. Median follow-up duration of surviving patients is 10 years.
      RESULTS: The annual incidence of NHL in children younger than 15 years of age was
      9/million children, representing 6% of all childhood malignancies during the
      investigation time. The male-female ratio was 4.1:1.0. Immunologic marker studies
      were available for 64 of the 77 NHLs: 41 patients had B-cell, 17 had T-cell, and
      6 had Ki-1-positive anaplastic large cell lymphoma (ALCL). Two patients with Ki-1
      positive ALCL were originally thought to have malignant histiocytosis and
      Langerhans cell histiocytosis (LCH), respectively. Treatment was the most
      significant prognostic factor; event-free survival (EFS) was 19% in the
      preprotocol era (1975 to 1979) and 74% from 1980 to 1994. Other than treatment,
      stage was the most significant prognostic factor; EFS was 86% for patients (1980
      to 1994) with stage I or II disease and 64% for patients with stage III or IV
      disease, with a dismal prognosis for children with initial involvement of the
      bone marrow or central nervous system (EFS was 38% and 20%, respectively). Bulky
      disease and performance state at diagnosis were independent prognostic factors.
      The patterns of relapse, including early recurrence of the B-cell lymphomas, are
      in accordance with previous experience. CONCLUSION: The incidence of NHL was
      found to be somewhat higher than reported in our previous Nordic study. The
      higher incidence found in this study might be the result of the thorough data
      collection (based on hospital registry and cross-checked with all registries for
      malignant diseases in Sweden) or because reexamination of the tissue material was
      performed. A more pronounced male predominance than found in previous
      investigations was observed. The immunophenotypic distribution and the stage
      distribution is in accordance with earlier investigations. Treatment was the most
      important factor affecting outcome. A dramatic improvement of survival was seen
      with the introduction of intensive therapy; treatment success can be expected in
      86% of children with localized disease and 64% of children with extensive
      disease. The absence of improvement in survival despite further treatment
      stratification with the introduction of the BFM protocol for B-cell-NHL is
      surprising. LSA2L2-like protocols seem to be as effective. Future studies on
      treatment of NHL must also concentrate on reducing the intensity of therapy in
      patients with lower risk disease to minimize late toxic effects.

PMID- 10206456
TI  - Nasogastric tube feedings in children with high-risk cancer: a pilot study.
AB  - PURPOSE: To avoid the cost and complications of total parenteral nutrition (TPN),
      this study was initiated to determine the feasibility of administrating
      nasogastric tube feedings in children receiving intensive chemotherapy (CTX) or
      bone marrow transplantation (BMT). PATIENTS AND METHODS: Seventeen children (aged
      2 to 19 years) were entered into the study. Continuous nasogastric feedings of a
      glutamine-supplemented elemental diet were administered during CTX and at the
      time of rehospitalization for fever, neutropenia, and mucositis. RESULTS:
      Fourteen children were treated with CTX and 3 with BMT. Enteral tube feedings
      were administered for 216 days; each patient received a mean of 12.7 days. The
      tubes were generally well tolerated, and there were no instances of sinusitis or
      epistaxis. Six children received TPN in addition to enteral feedings. The
      hospital charges for the enteral feedings were $25,348, compared to $112,299 for
      the same number of days of TPN. CONCLUSIONS: Nasogastric tube insertion and
      enteral tube feedings in children receiving intensive CTX or BMT can be
      accomplished with minimal complications and significant cost savings when
      compared to TPN.

PMID- 10206457
TI  - Late effects of treatment for germ cell tumors during childhood and adolescence.
AB  - PURPOSE: To evaluate the long-term sequelae of treatment for malignant germ cell
      tumors (GCT) during childhood and adolescence. PATIENTS AND METHODS: Of 128
      patients treated for GCT at St. Jude Children's Research Hospital between 1962
      and 1988, 73 are long-term survivors (continuously disease-free for > or =5 years
      after diagnosis), with a median follow-up of 11.3 years). Survivors' ages at
      diagnosis ranged from birth to 18.3 years (median, 9.2 years); 64% (47 patients)
      were female. Initial surgical resection was followed by observation for stage I
      germinomas (n = 2), testicular tumors (n = 13), and selected cases of ovarian or
      sacrococcygeal tumors (n = 2), and by radiation therapy (RT) for patients with
      stage II to III germinoma (n = 8). The remaining 48 patients received
      postoperative chemotherapy (vincristine, dactinomycin, and cyclophosphamide [VAC]
      +/- doxorubicin, 1962 to 1978; VAC and/or cisplatin, vinblastine, and bleomycin
      [PVB], 1979 to 1988). RT was added to the chemotherapy for 21 patients. Late
      complications involving various organ systems and their relationship to treatment
      were evaluated. RESULTS: More than two-thirds of long-term survivors (n = 50) had
      at least 1 complication, and half (n = 38) had > 1 organ system affected. The
      systems most often involved included the musculoskeletal (41% of survivors),
      endocrine (42%), cardiovascular (16% excluding those who had only abnormal chest
      radiograph), gastrointestinal (25%), genitourinary tract (23%), pulmonary (19%),
      and neurologic (16%) systems. High-frequency hearing loss occurred in 58% (11 of
      19) of patients treated with cisplatin. Musculoskeletal, gastrointestinal, and
      urinary tract abnormalities were most frequent in patients whose treatment
      included RT. CONCLUSIONS: A high frequency of late effects after treatment for
      pediatric GCT, particularly in patients who received RT, was demonstrated.
      Treatment sequelae could be anticipated from the intensity and type of
      therapeutic modalities. Treatment-directed screening evaluations may improve
      quality of life in long-term survivors of pediatric GCT through timely
      identification of sequelae that can be prevented or ameliorated.

PMID- 10206458
TI  - Hemolytic uremic syndrome in children: platelet aggregation and membrane
      glycoproteins.
AB  - PURPOSE: Several mechanisms have been proposed to explain the fibrin-platelet
      thrombosis at the microcirculation level in the different clinical conditions of
      hemolytic uremic syndrome (HUS). The relationships between platelet structure and
      function during the first 4 weeks of evolution of the disease were studied to
      understand the mechanism of platelet alteration. PATIENTS AND METHODS:
      Coagulation parameters, platelet counts, and aggregation were studied in 49
      children, and membrane glycoproteins (GPs) in 20 of the 49 children (mean age, 17
      months) with HUS (Group 2) were studied during the first 4 weeks of evolution of
      the disease. RESULTS: No disseminated intravascular coagulation was found in
      patients with recurrent or persistent thrombocytopenia. Platelet aggregation was
      sequentially performed during the first weeks of evolution. All patients had a
      functional decrease in the acute period of HUS. Platelet GPs GPIb, GPIIbIIIa,
      GPIIb, and GPIIIa were evaluated. GPIIbIIIa complex presented low level and never
      reached normal values during the first 4 weeks of disease. CONCLUSIONS: Platelet
      alterations are probably caused by multiple mechanisms: "exhausted" platelets,
      structural membrane alterations caused by arginine-glycine-aspartic peptide
      blockade, or diminished or nonfunctional membrane GPIb and GPIIbIIIa complexes.

PMID- 10206460
TI  - Iron chelation with deferoxamine: comparing the results of a critical pathway to
      a national survey.
AB  - PURPOSE: The clinical outcomes of an institution's critical pathway that uses a
      comprehensive approach to serum ferritin management are reported. The results of
      this center are compared with the results of a national survey of deferoxamine
      (DFO) use and serum ferritin level outcomes. METHODS: Current DFO dosing and
      serum ferritin levels of 38 patients at this center were summarized. A
      questionnaire was then sent to 98 centers throughout the United States requesting
      information on criteria for beginning treatment with DFO, administration methods,
      dose modifications, and serum ferritin levels. RESULTS: The application of a
      critical pathway in this program resulted in 29 of 38 patients maintaining serum
      ferritin levels <2,000 ng/mL. Of the 42 institutions that responded to the
      survey, 10 attained this ferritin level in > or =50% of their patients. Ferritin
      levels ranged from 500 ng/mL to >20,000 ng/mL, and wide variations were reported
      in all study parameters. CONCLUSIONS: Iron overload can be effectively managed
      with alteration of DFO doses and routes using a consistent approach. Modification
      of administration methods, including administration of DFO during red blood cell
      transfusions, are indicated to attain ferritin levels of <2,000 ng/mL.

PMID- 10206459
TI  - Tonsillectomy, adenoidectomy, and myringotomy in sickle cell disease:
      perioperative morbidity. Preoperative Transfusion in Sickle Cell Disease Study
      Group.
AB  - PURPOSE: To compare the rates of perioperative morbidity of patients with sickle
      cell anemia who were randomly assigned to 2 preoperative transfusion regimens and
      to identify predisposing factors for perioperative complications. PATIENTS AND
      METHODS: Investigators at 36 centers enrolled 118 patients who were scheduled to
      have elective surgery and agreed to randomization between 2 preoperative
      transfusion regimens. Forty-seven subjects were enrolled but not randomized,
      including 20 who were not transfused before surgery. Perioperative management was
      based on a prescribed care plan. RESULTS: Tonsillectomy and/or adenoidectomy (TA)
      were performed on 136 persons, and 29 had myringotomy as their primary procedure.
      There were no differences in the frequency of complications between the
      randomized groups. The serious, non-transfusion complication rates for randomized
      patients were 32% (34 of 107) for TA and 36% (4 of 11) for myringotomy. A history
      of pulmonary disease was a predictor of postoperative sickle cell-related events
      for patients undergoing TA surgery. CONCLUSIONS: The more intensive transfusion
      regimen did not result in fewer perioperative complications. The high frequency
      of complications emphasizes the need for anticipatory management of persons
      undergoing TA. A history of pulmonary disease identifies patients at increased
      risk for sickle cell-related events after TA surgery. Patients undergoing
      myringotomy have a low frequency of sickle cell-related events but a significant
      frequency of other serious perioperative complications.

PMID- 10206461
TI  - Quantification of liver iron overload by T2 quantitative magnetic resonance
      imaging in thalassemia: impact of chronic hepatitis C on measurements.
AB  - PURPOSE: Measurement of liver T2 values seems to be an accurate and sensitive
      magnetic resonance imaging (MRI) method for the quantification of liver
      hemosiderosis in multiple transfused patients with thalassemia. Because many of
      these patients have coexistent chronic hepatitis C virus (HCV) infection, the
      effect of inflammatory changes on liver T2 values was assessed. MATERIALS AND
      METHODS: Liver MRI studies of 35 HCV+ and 17 HCV- patients with beta-thalassemia,
      9 HCV+ patients without thalassemia, and 10 healthy controls of the same age
      range (13 to 32 years) were reviewed. Iron status was assessed by serum ferritin
      in all patients, and determination of liver iron concentration (LIC) was
      available in 16 HCV+ patients with thalassemia. Histologic activity index (HAI)
      and grades of siderosis were evaluated in all HCV+ patients with thalassemia.
      RESULTS: Patients with thalassemia had significantly lower T2 values (P < 0.0001)
      than subjects without thalassemia, whereas no difference existed between HCV+
      patients without thalassemia and healthy controls. In HCV+ patients, LIC
      correlated more nearly with T2 values (r = 0.93) than with serum ferritin (r =
      0.73). T2 values were not influenced by HAI score or fibrosis. CONCLUSION: Liver
      T2 values were found to be more accurate than serum ferritin in predicting liver
      iron overload and were not influenced by the presence of chronic hepatitis C.
      Therefore, MRI could serve as a noninvasive alternative to liver biopsy for the
      quantification of hemosiderosis in HCV+ patients with thalassemia.

PMID- 10206462
TI  - Intracranial germ cell tumors in children with and without Down syndrome.
AB  - PURPOSE: Two Chinese children with Down syndrome affected by intracranial germ
      cell tumors are described. Because they represent two of eight affected patients
      in the current series from 1990 to 1996, it is postulated that such occurrence
      may be more than a coincidental event. PATIENTS AND METHODS: Two children with
      Down syndrome developed germ cell tumors in atypical intracranial sites that
      affected basal ganglion and cerebellum. The pathology showed germinoma and yolk
      sac tumor, respectively. These were treated by radical surgical resection and
      chemotherapy with cisplatin, etoposide, and bleomycin, but without radiotherapy.
      RESULTS: One patient survived 3 years without radiologic evidence of tumor. The
      other died from infective complications caused by severe myelosuppression after
      chemotherapy. CONCLUSIONS: Subtle neurologic manifestations in developmentally
      handicapped patients with intracranial space-occupying lesions could result in
      delayed diagnosis. Children with Down syndrome suffering from brain tumors may
      have a higher chance for germ cell tumors. Assay for alpha-fetoprotein and beta
      human chorionic gonadotrophin could hasten diagnosis in some cases. This
      observation and review of literature suggest an increased risk of developing
      intracranial germ cell tumors in subjects with Down syndrome.

PMID- 10206463
TI  - Congenital leukemia: successful treatment of a newborn with t(5;11)(q31;q23).
AB  - A male neonate presented with a high white cell count, an 11q23 translocation,
      and M5b leukemia. He was treated at 3 days of age with intensive combination
      chemotherapy after progressing despite exchange transfusions. The patient
      achieved complete remission at 28 days of age. Therapy was completed at the age
      of 6 months. At the time of this report, the patient is 17 months old and remains
      in remission. Twenty-nine patients with congenital acute myeloid leukemia were
      also reviewed. Twenty of these patients received varying therapies. Ten of the
      treated patients achieved complete remission; two died of toxicity; and eight
      died of progressive disease. Two patients had a translocation affecting 11q23.
      Congenital leukemia is a rare and usually fatal condition in patients without
      Down syndrome. The patient reported here shows that survival may be achieved with
      very intensive chemotherapy plus supportive care, despite extremely high white
      blood cell counts and unfavorable translocation.

PMID- 10206464
TI  - Neurofibromatosis-Noonan syndrome and acute lymphoblastic leukemia: a report of
      two cases.
AB  - Two boys with neurofibromatosis-Noonan syndrome in whom acute lymphoblastic
      leukemia (ALL) developed are described. Both patients demonstrated B-lineage
      leukemias with normal cytogenetics. They were treated with combination
      chemotherapy and remain in remission off therapy. Patients with neurofibromatosis
      Noonan syndrome may be at increased risk for ALL.

PMID- 10206465
TI  - Successful therapy in a child with a congenital peripheral medulloepithelioma and
      disruption of hindquarter development.
AB  - PURPOSE: Medulloepithelioma is an embryonal multipotential neuroepithelial tumor
      with a striking potential for divergent differentiation. It is usually
      intraocular or intracerebral and associated with a good prognosis only if
      completely surgically excised. Data regarding therapy in children with
      incompletely resected tumors are limited. PATIENT AND METHODS: A girl was born
      with a large, peripheral, congenital medulloepithelioma associated with complete
      absence of the left hindquarter and anus. Plain film, ultrasonography, and
      magnetic resonance imaging demonstrated complete absence of the left kidney and
      hemipelvis. A subtotal resection of the mass and reconstruction of the tumor
      related anatomical defects were performed. RESULTS: Pathologic examination showed
      neuroglia and pseudostratified neuroectoderm diagnostic of medulloepithelioma.
      She was treated with multiagent chemotherapy including vincristine, cisplatin,
      cyclophosphamide, carboplatin, and etoposide. She is now 50 months of age and
      developing normally without recurrent disease. CONCLUSIONS: A child with an
      incompletely resected congenital peripheral medulloepithelioma who has
      experienced long-term disease-free survival after treatment with chemotherapy is
      described. This report supports a role for adjuvant chemotherapy in the treatment
      of children with peripheral medulloepithelioma.

PMID- 10206467
TI  - Transient thrombocytopenia after cardiac surgery in infants with Down syndrome.

PMID- 10206466
TI  - Delayed methotrexate clearance in a patient with sickle cell anemia and
      osteosarcoma.
AB  - A 15-year-old girl with homozygous sickle cell anemia (HbSS) and osteosarcoma is
      described. Delayed clearance of methotrexate (MTX) after the second course of
      high-dose MTX (HDMTX) led to the development of renal and hepatic toxicities.
      Rescue was accomplished with high-dose leucovorin, intravenous carboxypeptidase
      G2, and thymidine. Although the renal and hepatic abnormalities resolved, focal
      tonic-clonic seizures developed, accompanied by abnormal brain imaging. Four
      weeks after this episode, all clinical and biochemical abnormalities resolved.
      Preexistent end-organ damage associated with HbSS may compromise the ability to
      deliver high-dose chemotherapy with curative intent in patients with malignant
      disease.

PMID- 10206468
TI  - Thrombocytopenia after human herpesvirus-7 infection in a patient with DiGeorge
      syndrome.

PMID- 10206470
TI  - Subcellular localization of mRNA in neuronal cells. Contributions of high
      resolution in situ hybridization techniques.
AB  - The development of technologies for high-resolution nucleic acid localization in
      cells and tissues has contributed significantly to our understanding of
      transcriptional and translational regulation in eukaryotic cells. These methods
      include nonisotopic in situ hybridization methods for light and electron
      microscopy, and fluorescent tagging for the study of nucleic acid behavior in
      living cells. In situ hybridization to detect messenger RNA has led to the
      discovery that individual transcripts may be selectively targeted to particular
      subcellular domains. In the nervous system, certain species of mRNA have been
      localized in distal processes in nerve cells and glia. Direct visualization of
      mRNA and its interactions with subcellular features, such as synaptic
      specializations, cytoskeletal elements, and nuclear pores, have been achieved. Of
      particular interest is the presence of mRNA and ribosomes in dendrites, beneath
      synaptic contacts, suggesting the possibility of synaptic regulation of protein
      synthesis. The following article will describe the application of high-resolution
      in situ hybridization and live imaging techniques to the study of mRNA targeting
      in neurons.

PMID- 10206471
TI  - Regulation of oligodendrocyte development.
AB  - Oligodendrocytes are the cells responsible for the formation of myelin in the
      central nervous system. Recent studies demonstrated that cells of the
      oligodendrocyte lineage initially arise in distinct regions of the ventricular
      zone during early development. These cells or their progeny migrate to developing
      white matter tracts where they undergo the majority of their proliferation and
      subsequently differentiate into myelinating cells. Oligodendrocyte-precursor cell
      proliferation is regulated by a number of distinct growth factors that act at
      distinct stages in the lineage and the final number of oligodendrocytes in any
      region of the CNS is regulated by local influences. A density-dependent feedback
      inhibition of proliferation reduces the responsiveness of the cells to their
      growth factors and the final matching of oligodendrocyte and axon number is
      accomplished through the local regulation of cell death. In this review, we
      discuss the major factors that regulate three distinct stages in the development
      of the oligodendrocyte lineage: The initial induction of oligodendrocyte
      progenitors, the regulation of expansion and dispersion of the committed
      precursor cell population, and the final regulation of oligodendrocyte precursor
      number through the local inhibition of oligodendrocyte precursor proliferation
      and cell death.

PMID- 10206473
TI  - Relevance of divalent cations to ATP-driven proton pumping in beef heart
      mitochondrial F0F1-ATPase.
AB  - The ATP hydrolysis rate and the ATP hydrolysis-linked proton translocation by the
      F0F1-ATPase of beef heart submitochondrial particles were examined in the
      presence of several divalent metal cations. All Me-ATP complexes tested sustained
      ATP hydrolysis, although to a different extent. However, only Mg- and Mn-ATP
      dependent hydrolysis could sustain a high level of proton pumping activity, as
      determined by acridine fluorescence quenching. Moreover, the Km of the Me-ATP
      hydrolysis-induced proton pumping activity was very similar to the Km value of Me
      ATP hydrolysis. Both oligomycin and DCCD caused the full recovery of the
      fluorescence, providing clear evidence for the association of Mg-ATP hydrolysis
      with proton translocation through the F0F1-ATPase complex. In contrast, with
      other Me-ATP complexes, including Ca-ATP as substrate, the proton pumping
      activity was undetectable, implicating an uncoupling nature for these substrates.
      Attempts to demonstrate the involvement of the epsilon subunit of the enzyme in
      the coupling mechanism failed, suggesting that the participation of at least the
      N-terminal segment of the subunit in the coupling mechanism of the mitochondrial
      enzyme is unlikely.

PMID- 10206474
TI  - Cooperativity between the enzymatic sites of F1-ATPase revisited by the use of
      HPLC methods.
AB  - The fundamental question of the cooperativity between the enzymatic sites of F1
      ATPase is examined in the light of new measurements of the enzymatic rate of ATP
      hydrolysis by CF1, the enzyme isolated from spinach chloroplasts. The
      experimental data, obtained with a chromatographic method, fit a model that
      involves two kinds of independent enzymatic sites working with metal-free ATP,
      with no need of cooperativity between the sites. Binding measurements between ADP
      or ATP and CF1 by the chromatographic method of Hummel and Dreyer (1962) also
      support this conclusion. The present data and interpretation are in agreement
      with those reported recently (Reynafarje and Pedersen, 1996) which show that the
      first order rate constant of ATP hydrolysis by MF1, the analogous enzyme from
      mitochondria, is virtually constant under experimental conditions involving
      either unisite or multisite hydrolysis of ATP. The present data and
      interpretation are discussed together with those reported previously, in
      particular with regard to the methods that were used to support the commonly
      accepted opposite viewpoint.

PMID- 10206472
TI  - Cardiolipins and mitochondrial proton-selective leakage.
AB  - The proton-selective leak (State 4 respiratory rate) but not delta psi, in
      mitochondria from thyroid-sensitive tissues, responds to in vivo stimuli in
      unique correlation with changes in cardiolipins, saturated and mono-unsaturated
      (extended) fatty acyl contents, cardiolipins/phospholipids ratios, and/or
      membrane outer-sidedness. Liver mitochondrial State 4 respiration, basal in
      fasted rats, contributes little to resting metabolic rate in fed rats, where
      State 3 depresses delta psi. In a proposed model, an essential inner-membrane
      outer-surface proton antenna collects protons and donates them, via a water
      shuttle, to transmembrane porters: transient water-molecule-chains between
      extended phospholipid acyls; protonophores, and uncoupling proteins. Only
      cardiolipin microdomains can donate, from an anomalously-dissociating phosphate
      group in each headgroup; unadapted cardiolipins have few conducting water chains.
      Thyroid states regulate each cardiolipin property, and are permissive, via the
      proton antenna, for proton leaks, including those through adapted and possibly
      constitutive BAT and ectopic uncoupling proteins. Slow leakage in liposomes may
      reflect insufficient cardiolipin proton antennas.

PMID- 10206475
TI  - Kinetics of the reconstituted tricarboxylate carrier from eel liver mitochondria.
AB  - The tricarboxylate carrier from eel liver mitochondria was purified by
      chromatography on hydroxyapatite and Matrix Gel Blue B and reconstituted into
      liposomes by removal of the detergent with Amberlite. Optimal transport activity
      was obtained by using a phospholipid concentration of 11.5 mg/ml, a Triton X-
      114/phospholipid ratio of 0.9, and ten passages through the same Amberlite
      column. The activity of the carrier was influenced by the phospholipid
      composition of the liposomes, being increased by cardiolipin and
      phosphatidylethanolamine and decreased by phosphatidylinositol. The reconstituted
      tricarboxylate carrier catalyzed a first-order reaction of citrate/citrate or
      citrate/malate exchange. The maximum transport rate of external [14C]citrate was
      9.0 mmol/min per g of tricarboxylate carrier protein at 25 degrees C and this
      value was virtually independent of the type of substrate present in the external
      or internal space of the liposomes. The half-saturation constant (Km) was 62
      microM for citrate and 541 microM for malate. The activation energy of the
      citrate/citrate exchange reaction was 74 kJ/mol from 5 to 19 degrees C and 31
      kJ/mol from 19 to 35 degrees C. The rate of the exchange had an external pH
      optimum of 8.

PMID- 10206476
TI  - Energetic and morphological plasticity of C6 glioma cells grown on 3-D support;
      effect of transient glutamine deprivation.
AB  - The energetic metabolism of rat C6 glioma cells has been investigated as a
      function of the proliferative and differentiation states under three-dimensional
      (3-D) growing conditions on microcarrier beads. First, the transient deprivation
      of glutamine from the culture medium induced a marked decrease in the growth rate
      and a differentiation of C6 cells through the oligodendrocytic phenotype. Second,
      the respiratory capacity of the C6 cells during short-term subcultures with or
      without glutamine continuously declined as a function of the cell density, in
      part due to the mitochondrial content decrease. During the transition from the
      early exponential to the plateau growth phase in glutamine-containing medium, the
      oxygen consumption rate per single cell decreased concomitantly with a decrease
      in the glucose consumption and lactate production rates. This phenomenon led to a
      sixfold decrease in the total ATP production flux, without significantly
      affecting the cellular ATP/ADP ratio, thus indicating that some ATP-consuming
      processes were simultaneously suppressed during C6 proliferation. In glutamine
      free medium, the cellular ATP/ADP ratio transiently increased due to growth
      arrest and to a reduced ATP turnover. Moreover, the results indicated that
      glutamine is not an essential respiratory substrate for rat C6 glioma under short
      term glutamine deprivation. Worth noting was the high contribution of the
      mitochondrial oxidative phosphorylation toward the total ATP synthesis (about
      80%), regardless of the proliferation or the differentiation status of the C6
      cells.

PMID- 10206478
TI  - Workup of a patient with familial pancreatic cancer.

PMID- 10206477
TI  - Fast- and slow-gating modes of the sodium channel are altered by a paramyotonia
      congenita-linked mutation.
AB  - We have studied the expression in frog oocytes of the alpha subunit of the rat
      skeletal muscle sodium channel mutation T1306M, homologous to the mutation T1313M
      of the human isoform that causes the muscular hereditary disease paramyotonia
      congenita. Wild-type (WT) channels show a bimodal behavior, with two gating modes
      characterized by inactivation time constants that differ at least by one order of
      magnitude and with voltage dependencies shifted by +27 mV in the slow mode (M2)
      relative to the fast (M1) mode. In the myopathy-linked mutant the propensity of
      the channel for the mode M2 is increased fourfold and the kinetics and voltage
      dependence of inactivation in both modes are altered. In mode M1, the onset of
      inactivation is faster and the recovery from inactivation is slower whereas both
      processes are slowed in mode M2. The half-inactivation potential of both modes is
      shifted by the mutation to positive potentials. Coexpression of beta subunit
      causes a threefold reduction of the M2 propensity of both WT and T1306M channels,
      with small changes in the voltage dependency and kinetic properties of
      inactivation. All the changes are consistent with the hyperexcitability of the
      muscle fibers observed in patients affected by potassium-aggrevated myotonia
      (PAM).

PMID- 10206469
TI  - Regulation of ion channel expression in neural cells by hormones and growth
      factors.
AB  - Voltage-and ligand-gated ion channels are key players in synaptic transmission
      and neuron-glia communication in the nervous system. Expression of these proteins
      can be regulated at several levels (transcriptional, translational, or
      posttranslational) and by multiple extracellular factors in the developing and
      mature nervous system. A wide variety of hormones and growth factors have been
      identified as important in neural cell differentiation, which is a complex
      process involving the acquisition of cell-type-specific ion channel phenotypes.
      Much literature has already accumulated describing the structural and functional
      characteristics of ion channels, but relatively little is known about the factors
      that influence their synthesis and cell surface expression, although this area
      has generated considerable interest in the context of neural cell development.
      This article reviews several examples of regulated expression of these channels
      by cellular factors, namely peptide growth factors and steroid hormones, and
      discusses, where applicable, current understanding of molecular mechanisms
      underlying such regulation of voltage-and neurotransmitter-gated ion channels.

PMID- 10206479
TI  - Increased angiogenin expression in obstructive chronic pancreatitis surrounding
      pancreatic cancer but not in pure chronic pancreatitis.
AB  - We previously demonstrated the increased expression of angiogenin (ANG) in
      pancreatic cancer and its relation to cancer aggressiveness; however, the
      expression patterns and the roles of angiogenin in chronic pancreatitis are still
      unknown. We investigated the expression of ANG both in the tissues and in the
      sera of chronic pancreatitis patients (pure chronic pancreatitis) by using in
      situ hybridization, Western blot analysis, and enzyme-linked immunosorbent assay.
      In situ hybridization revealed no detectable ANG messenger RNA (mRNA) signals in
      all tissues of pure chronic pancreatitis and normal pancreas. Only a small amount
      of protein band expression was obtained in all of the protein lysates of pure
      chronic pancreatitis and normal pancreas. Accordingly, there was no significant
      difference between the mean serum ANG concentration of chronic pancreatitis
      patients (352.1+/-72.5 ng/ml) and that of healthy volunteers (357.6+/-45.2
      ng/ml). By contrast, acinar cells and interstitial fibroblasts in the tissues
      surrounding pancreatic cancer showed increased ANG mRNA expression. Strong
      protein band expression was obtained in the protein lysates of pancreatic cancer
      surrounding tissue, and mean serum ANG concentration was increased in pancreatic
      cancer patients. These findings suggest that ANG expression is increased in
      pancreatic cancer surrounding tissue but is not increased in pure chronic
      pancreatitis, and that ANG is potentially involved in the pancreatic cancer
      microenvironment rather than the establishment of pure chronic pancreatitis.

PMID- 10206480
TI  - Amelioration of rat cerulein pancreatitis by guamerin-derived peptide, a novel
      elastase inhibitor.
AB  - Increased activity of various proteases is observed in both human and
      experimental pancreatitis; however, the information on the effects of specific
      protease inhibitors on the disease is limited. In this study we show that a novel
      elastase inhibitor, guamerin-derived synthetic peptide (GDSP), improves the
      parameters of cerulein-induced acute pancreatitis in the rat. The effects of GDSP
      on pancreatic weight, serum amylase and lipase, morphologic changes in the
      pancreas, neutrophil infiltration, and nuclear factor KB (NF-KB) activation were
      measured in rats infused with supramaximal dose of cerulein (5 (g/kg/h) for 6 h.
      The effects of GDSP were also measured on superoxide formation by activated human
      neutrophils. The effects of GDSP were compared with those of another elastase
      inhibitor, elastatinal. GDSP significantly inhibited edema formation, neutrophil
      infiltration, acinar cell damage, and plasma lipase and amylase increases caused
      by cerulein. GDSP also completely inhibited superoxide formation in the human
      neutrophils stimulated by N-formyl-methionine-leucine-phenyl-alanine (fMLP) or 12
      O-tetradecanoylphorbol-13-acetate (TPA). Elastatinal had some of the same effects
      as GDSP but was less potent and effective. These results demonstrate a beneficial
      effect of GDSP, a novel specific elastase inhibitor, on the development of rat
      cerulein pancreatitis.

PMID- 10206482
TI  - Behavior of serum interleukin 12 in human acute pancreatitis.
AB  - We evaluated the behavior of sera interleukin p70 (IL-12p70) and IL-12p40 in
      patients with acute pancreatitis. Twenty-three acute pancreatitis patients were
      studied (12 had severe pancreatitis and 11 had mild pancreatitis). Twenty healthy
      subjects were studied as controls. Serum concentrations of total IL-12, IL-12p70,
      IL-12p40, and IL-6 were determined in all subjects on admission to the hospital;
      in patients with acute pancreatitis, the serum levels of these molecules also
      were determined for the 5 days after admission. Acute pancreatitis patients had
      serum concentrations of total IL-12, IL-12p40, and IL-6 significantly higher (p <
      0.05) than those of the healthy subjects from the first to the sixth day of the
      study; serum concentrations of IL-12p70 were significantly higher in acute
      pancreatitis patients (p < 0.02) than in the healthy subjects on the first of the
      disease and significantly lower (p < 0.05) on the second, third, and fourth days
      of illness. Reduction of IL-12p70 in acute pancreatitis patients was not due to a
      failure of the monocytes because the production of IL-6 was increased. Increased
      amounts of IL-12p40 in acute pancreatitis patients may be responsible for their
      increased susceptibility to infection.

PMID- 10206481
TI  - Alteration of fibroblast growth factor and receptor expression after acute
      pancreatitis in humans.
AB  - After an episode of acute pancreatitis (AP) in humans, the pancreas exhibits
      varying degrees of fibrosis, acinar cell regeneration, and the formation of
      tubular complexes. The mechanisms underlying these changes are unknown. By using
      Northern blot analysis and immunohistochemistry, we assessed the expression and
      distribution of fibroblast growth factors (FGFs) and their receptor in human
      pancreatic tissues obtained from patients with AP. By comparison with the normal
      pancreas, acidic FGF (aFGF) and FGF-receptor 1 (FGFR-1, flg), mRNA levels were
      significantly decreased in human pancreatic tissues, which were obtained
      approximately 8 days after onset of AP. In the normal pancreas, acidic FGF, basic
      FGF, and FGFR-1 immunoreactivity was present at low to moderate levels in a
      heterogeneous pattern in the cytoplasm of acinar and ductal cells. Two patterns
      of immunoreactivity were observed in the AP group. In regions that have undergone
      necrosis, there was complete loss of aFGF, bFGF, and FGFR-1 immunostaining. In
      contrast, in the regenerating areas, aFGF and bFGF were readily evident in
      exocrine-type cells, in association with a marked increase in FGFR-1
      immunoreactivity. These findings indicate that FGF/receptor expression is altered
      after AP, and raise the possibility that FGFs may be involved in the process of
      pancreatic exocrine regeneration during recovery from AP.

PMID- 10206484
TI  - Irreversibility of nutritionally induced NIDDM in Psammomys obesus is related to
      beta-cell apoptosis.
AB  - Psammomys lapses into fully fledged diabetes when maintained on a high-energy
      diet. Progression to diabetes has been classified into stage A of normoglycemia
      and normoinsulinemia (<120 mg/ml and 100 mU/L, respectively); stage B of
      hyperinsulinemia (100-300 mU/L) with marked insulin resistance in the face of
      normoglycemia; stage C of pronounced hyperinsulinemia with hyperglycemia < or
      =500 mg/ml; stage D at 6-10 weeks after stage C, featuring further hyperglycemia
      and loss of insulin. Insulin resistance expressed in Psammomys at stages B and C
      was demonstrated by nonsuppression of the hepatic gluconeogenesis enzyme
      phosphoenolpyruvate carboxykinase by the endogenous hyperinsulinemia and by the
      reduced capacity of insulin to activate muscle and liver tyrosine kinase of the
      insulin receptor. Diabetes at stage C, but not at stage D, was fully reversed to
      stage A by restricting the food ration of animals by half (from 14 to 7 g/day)
      for 10-14 days. We examined islet beta cells of Psammomys in the four stages of
      progression to diabetes by staining for insulin as well as for apoptosis by the
      terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) and
      visualizing the biotin-labeled cleavage sites. Psammomys in stage A had insulin
      laden beta cells. In stage B, a hypertrophy and partial insulin depletion of beta
      cells was evident with negative TUNEL staining. In stage C, beta cells were
      markedly depleted of insulin, and their number within the islets decreased, but
      the TUNEL staining was virtually negative. In stage D, beta cells were markedly
      diminished within the islets, almost void of insulin, showing distinct TUNEL
      staining of beta cells. These results indicate that prolonged exposure of islets
      to in vivo hyperglycemia with beta-cell overtaxation induces nuclear
      disintegration with irreversible damage to the insulin-secretion apparatus. This
      precludes the return to normalcy by restricting the food intake of Psammomys. The
      appearance of cells with TUNEL-positive staining may serve as a marker of
      impending irreversibility of nutritionally induced diabetes.

PMID- 10206483
TI  - Effect of insulin and glucose on basal and cholecystokinin-stimulated exocrine
      pancreatic secretion in humans.
AB  - Pancreaticobiliary secretion is reduced during acute hyperglycemia. In
      nondiabetics, this inhibitory effect also may result from hyperinsulinemia.
      Therefore we investigated the effects of acute hyperglycemia and euglycemic
      hyperinsulinemia on basal and cholecystokinin (CCK)-stimulated pancreaticobiliary
      secretion. Nine healthy volunteers (age, 22-52 years) were studied on three
      occasions in random order during (a) intravenous saline (control), (b)
      hyperglycemic hyperinsulinemic clamping (HG; plasma glucose at 15 mM), and (c)
      euglycemic hyperinsulinemic clamping (HI; plasma insulin at 150 mU/L, glucose at
      4-5 mM). Duodenal outputs of bilirubin, amylase, trypsin, and bicarbonate were
      measured under basal conditions and during CCK infusion (0.25 and 0.5 IDU/kg/h).
      Basal pancreaticobiliary secretion was significantly (p < 0.05) reduced during
      both HG and HI. During low-dose CCK stimulation, HG significantly (p < 0.05)
      reduced bilirubin and trypsin output compared with control. In contrast, HI did
      not significantly reduce pancreatic enzyme and bilirubin output during low-dose
      CCK infusion. During high-dose CCK infusion, neither HI nor HG influenced
      pancreatic enzyme and bilirubin output. Pancreatic bicarbonate output was not
      influenced by CCK and remained significantly (p < 0.05) reduced during HI and HG
      compared with control. It is concluded that during both acute hyperglycemia and
      euglycemic hyperinsulinemia, basal pancreaticobiliary secretion is significantly
      reduced. CCK-stimulated pancreatic enzyme and bilirubin output is significantly
      reduced only during hyperglycemia. The inhibitory effect of hyperglycemia on
      pancreaticobiliary secretion in healthy volunteers may occur independent of
      insulin.

PMID- 10206485
TI  - Islet amyloid polypeptide and insulin relationship in a longitudinal study of the
      genetically obese (ob/ob) mouse.
AB  - Obese mice (Umea ob/ob) and their lean litter-mates were investigated from 7 to
      52 weeks of age with respect to the plasma concentration of islet amyloid
      polypeptide (IAPP) and insulin. Plasma levels of IAPP were highly elevated in the
      ob/ob mice and remained unchanged until age 33 weeks, after which a sudden
      significant increase occurred at age 40 weeks. The plasma concentration of
      insulin gradually increased from start to end and reached extremely high levels.
      In the lean mice, there were no age-related differences in plasma levels of IAPP
      and insulin, being of the same magnitude as in normal NMRI mice. The plasma
      IAPP/insulin molar ratio was similar in lean and obese mice until age 14 weeks.
      At 21 weeks, the ratio in the ob/ob mice had decreased dramatically and remained
      markedly (sixfold) lower than in the lean mice until the end of the study. The
      IAPP concentration in the pancreata of 21-week-old ob/ob mice was 25-fold higher
      than that in the lean mice. Immunohistochemically, a majority of the ob/ob mice
      displayed enlarged and more numerous pancreatic islets, compared with the lean
      mice, and the IAPP- and insulin-labeling intensity was equal for all animals. At
      the electron-microscopic level, there was an increase in the number of IAPP- and
      insulin-immunoreactive gold particles per whole granule area as well as per core
      granule area. We conclude that the dramatically increased IAPP levels in severely
      hyperinsulinemic ob/ob mice may be of importance for the development of insulin
      resistance. Further, the disproportionate secretion of IAPP and insulin in the
      adult obese mouse might indicate a disturbed negative feedback effect of IAPP on
      insulin secretory mechanisms, resulting in very high plasma insulin levels.

PMID- 10206486
TI  - Interactions between vitamin E and glucose on B-cell functions in the rat: an in
      vivo and in vitro study.
AB  - Hyperglycemia exerts negative effects on B-cell functions that may involve
      oxidative stress. This was tested for by investigating effects of D-alpha
      tocopherol (vitamin E), known as a free radical scavenger, on B-cell functions.
      For in vivo testing, rat pancreatic islets were transplanted syngeneically under
      the kidney capsule in streptozotocin-induced diabetic rats. Transplanted rats
      were treated with D-alpha-tocopherol (40 mg/kg, intraperitoneally injected every
      other day) or soybean oil for 2 or 6 weeks. Graft-bearing kidneys were then
      perfused and insulin release was measured after stimulation sequentially with
      glucose (27 mmol/L) and L-arginine (10 mmol/L). D-alpha-tocopherol treatment for
      2 or 6 weeks failed to restore glucose-induced insulin secretion, whereas
      treatment for 2 but not for 6 weeks enhanced basal insulin release (by 24%, p <
      0.05) and arginine-induced release (by 79%, p < 0.05). Treatment did not affect
      graft content of preproinsulin mRNA. The presence of D-alpha-tocopherol (50
      microg/ml) in vitro enhanced glucose (27 mmol/L)-stimulated insulin release from
      batch-type incubated islets by 33% (p < 0.05). Exposing islets to D-alpha
      tocopherol for 1 day in the presence of 38 mmol/L glucose enhanced glucose
      stimulated insulin release (by 25%, p < 0.05), L-arginine-stimulated release (by
      37%, p < 0.05) and elevated islet insulin content (by 20%, p < 0.05). These
      effects of exposure to D-alpha tocopherol were lost when the culture period was
      extended up to 3 weeks. It is concluded that D-alpha-tocopherol exerts moderate
      beneficial effects on B-cell functions during short to intermediate length of
      high glucose exposure. These effects are, however, insufficient to support a
      major role for oxidative stress behind glucotoxicity toward B cells.

PMID- 10206487
TI  - The role of CD8+ cells, cell degeneration, and Fas ligand in insulitis after
      intraperitoneal transfer of NOD splenocytes.
AB  - Cells expressing CD4, CD8, CD18, CD49d/CD29, CD44, CD54, CD80, CD86, CD106,
      CD11b/CD18 or DNA breaks were stained in the pancreases of female or male scid/
      scid mice after adoptive transfer of lymphocytes from older than 12-week female
      nonobese diabetic (NOD) or Balb/c mice. After intraperitoneal adoptive transfer
      of NOD splenocytes to female severe combined immunodeficiency (scid)/scid mice,
      in situ end labeling (ISEL)+ as well as CD80+ and CD86+ cell infiltrates appeared
      first in the blood vessel walls and pancreatic interstitial tissue at 2-3 weeks
      after transfer. CD4+, CD8+, CD18+, CD44+, CD54+, and CD106+ cells then encircled
      and invaded some islets of the scid/scid mice 2 to 7 weeks after transfer. Cells
      expressing these surface components, except CD8, were present also in the Balb/c
      mice, but as individual cells, not as infiltrates. CD8+ cells were observed in
      the pancreases of all NOD splenocyte-injected scid mice at 2, 3, 4, 6, and 7
      weeks after transfer, but in none of the Balb/c splenocyte-injected scid mice.
      Some scid/scid mice injected with NOD splenocytes also developed severe
      noninfectious diarrhea and cachexia 4 weeks after transfer. ISEL+ cells were
      observed in the pancreases of NOD splenocyte-injected female scid mice at all
      times after transfer, especially in the blood vessel walls and in the islets. Fas
      ligand was not present in Western blotting. It is proposed that apoptosis
      commonly occurs in islet-infiltrating lymphocytes and that in the scid/scid
      adoptive-transfer model, the first islet-infiltrating cells are destroyed by
      programmed cell death independent of Fas ligand. Further, CD8+ T lymphocytes
      inevitably play a central role in intraperitoneal adoptive transfer of insulitis.

PMID- 10206488
TI  - Detection of K-ras and p53 gene mutations in pancreatic juice for the diagnosis
      of intraductal papillary mucinous tumors.
AB  - The aim of this study was to investigate mutations of the K-ras oncogene and the
      p53 tumor suppressor gene in pancreatic juice and to evaluate our method for the
      diagnosis of intraductal papillary mucinous tumors (IPMT). Pancreatic juice was
      collected endoscopically from 12 patients with IPMT who underwent surgical
      resection (eight carcinomas and four adenomas) and eight cases without evident
      pancreatic diseases. DNA was extracted and both genes were examined by polymerase
      chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis and
      direct sequencing. In addition, surgically resected specimens were analyzed for
      both genes by the same methods, and p53 overexpression was investigated
      immunohistochemically. K-ras point mutations were detected in pancreatic juice
      from all 12 patients (100%) and p53 mutations were detected in five of 12 (42%).
      They were detected not only in carcinoma but also in adenoma and there was no
      difference between the mutations detected in pancreatic juice and surgical
      specimens. No mutations were found in any cases without pancreatic diseases.
      These findings suggest that alterations of K-ras and p53 gene are common events
      in the development of IPMT and that genetic analysis of them in pancreatic juice
      can be a useful tool for the clinical diagnosis of IPMT before surgery.

PMID- 10206489
TI  - Modulation of external pancreatic secretion by endogenous norepinephrine: study
      with a norepinephrine uptake blocker in the rat.
AB  - The effect of endogenous catecholamines on pancreatic secretion was analyzed with
      nisoxetine, a specific norepinephrine uptake blocker, and specific adrenoceptor
      antagonists in anesthetized acute fistula rats. Nisoxetine was administered alone
      or with alpha-1 (prazosin), alpha-2 (idazoxan or yohimbine), or beta
      (propranolol) adrenoceptor antagonists. Pancreatic secretion was measured in
      basal conditions or after stimulation by 2-deoxy-D-glucose (2DG), electrical
      vagal stimulation, or acetylcholine. (a) Basal. Nisoxetine alone had no effect.
      Associated with idazoxan or yohimbine, nisoxetine produced a dose-related
      stimulation (p < 0.01) of water and electrolyte without changing protein output.
      Addition of propranolol abolished this stimulation. (b) 2DG. Nisoxetine inhibited
      2DG-induced secretion (p < 0.01). Idazoxan or yohimbine suppressed the nisoxetine
      inhibition of water and electrolyte output (p < 0.01) but had no effect on
      protein output, which was restored only by adding a mixture of idazoxan,
      prazosin, and propranolol. (c) Electrical stimulation. Nisoxetine did not modify
      water and electrolyte but inhibited protein response by 75%. Adding idazoxan to
      nisoxetine significantly increased (p < 0.01) water and bicarbonate response and
      partly restored protein response. Water and bicarbonate response was restored by
      propranolol, whereas protein response was only restored by adding a mixture of
      idazoxan, prazosin, and propranolol. (d) Nisoxetine did not modify pancreatic
      response to acetylcholine. In conclusion, endogenous norepinephrine affects the
      response to vagally mediated effects through several subtypes of adrenoceptors,
      without changing basal or acetylcholine stimulated secretion.

PMID- 10206490
TI  - Immunohistochemical and molecular analysis of giant cell carcinoma of the
      pancreas: a report of three cases.
AB  - We performed molecular biological studies as well as immunohistochemical analysis
      of three cases of giant cell carcinoma of the pancreas. Histologically, one case
      was a pleomorphic giant cell carcinoma consisting of pleomorphic giant/ small
      cells and spindle cells, one an osteoclast-like giant cell tumor composed of
      osteoclastoid giant cells and pleomorphic small cells, and one a pleomorphic
      giant cell carcinoma with osteoclastoid giant cells. Immunohistochemically,
      pleomorphic giant cells and small pleomorphic cells were positive for epithelial
      and mesenchymal markers throughout the cases. Osteoclastoid cells were strongly
      positive for PG-M1 (CD68), but negative for lysozyme and epithelial markers.
      Pleomorphic spindle cells showed the same immunoreactivity as pleomorphic
      giant/small cells. Genetically, all cases contained a mutation in the K-ras
      (codons 12, 13) oncogene, but neither p53 (exons 5-8) nor p16INK4 (exons 1, 2)
      gene mutations were found in any case. Furthermore, Loss of heterozygosity (LOH)
      of the p53, p161NK4. APC, and DPC4 gene loci was not found in any of the cases.
      Immunohistochemical study demonstrated this tumor to be of epithelial origin with
      mesenchymal differentiation. Genetically, initiation of the tumor is similar to
      that of usual ductal adenocarcinoma, but progression might be rather different.
      The peculiar histologic and biologic features of this tumor would be the result
      of changes in other functional genes.

PMID- 10206491
TI  - Sclerosing mesenteritis seen clinically as pancreatic pseudotumor: two cases and
      a review.
AB  - Sclerosing mesenteritis is an uncommon nonneoplastic inflammatory process in the
      mesentery that is seen as a pseudotumor, usually involving the small bowel
      mesentery, the mesenteric fat, and less commonly, the mesentery of the large
      bowel. We report two cases of sclerosing mesenteritis and review the literature
      on this rare disease. Both patients had pain, profound weight loss, and a mass on
      computed tomography (CT) scan of the abdomen. The provisional diagnosis was
      pancreatic neoplasm on the basis of clinical presentation and imaging studies.
      The diagnosis of sclerosing mesenteritis was established by histologic findings
      in biopsy material obtained at laparotomy in both cases. Interval histologic
      studies in one patient who had a high CA 19-9 level, progressive biliary ductal
      and partial duodenal compression, revealed a transitional histologic pattern from
      predominant inflammation and fat necrosis to predominant fibrosis. This may
      explain the varied descriptive terms used in the literature to describe this
      entity.

PMID- 10206492
TI  - Weber-Christian syndrome revealing intraductal papillary mucinous tumor of the
      pancreas.

PMID- 10206494
TI  - Tuberculosis elimination and the challenge of the long-term completer.

PMID- 10206493
TI  - Inhibitory effect of vacuolating toxin of Helicobacter pylori on enzyme secretion
      from rat pancreatic acini.

PMID- 10206495
TI  - Global tuberculosis control: an optimist's perspective.

PMID- 10206496
TI  - Completion of tuberculosis therapy for patients reported in the United States in
      1993.
AB  - SETTING: The highest priority for tuberculosis (TB) control is to ensure patients
      complete therapy. However, standardized, detailed evaluation of national
      performance on completion of therapy in the United States has been lacking. Since
      1982, the Centers for Disease Control and Prevention (CDC) has had a program
      objective that at least 90% of TB cases complete therapy. Since 1986, the
      standard of practice for patients with drug-susceptible TB has been 6 months of
      therapy. OBJECTIVE: To determine completion of therapy rates and duration of
      therapy for US TB patients reported in 1993. DESIGN: Expanded TB surveillance
      data on all US TB patients reported to the CDC in 1993 with initial therapy of
      two or more drugs were analyzed with respect to completion and duration of
      therapy. RESULTS: A disposition (reason therapy stopped) was obtained on 98.7% of
      23 489 treated patients. Overall, 91.2% of evaluable patients completed therapy.
      The overall completion rate at 12 months of therapy was 66.8%, and 90% completion
      was reached at 23 months. For patients with initially drug-susceptible TB,
      completion was 7.1% at 6 months, 66.5% at 12 months, and reached 90% at 22
      months. CONCLUSION: While completion rates ultimately exceeded 90% nationwide,
      there was considerable delay in reaching this objective, especially in patients
      with drug-susceptible TB. It is critical that health departments and health care
      providers identify and remedy any deficiencies responsible for prolonged therapy.

PMID- 10206497
TI  - Screening for infection and disease as a tuberculosis control measure among
      indigents in New York City, 1994-1997.
AB  - SETTING: Several social service agencies in New York City, and the Chest Clinic
      of Bellevue Hospital, a large public hospital. OBJECTIVE: To determine the
      utility of screening as a preventive and control measure among persons at risk
      for tuberculosis. DESIGN: Persons seeking social services at several private
      agencies in New York City were screened, and those with a positive skin test or
      symptoms suggestive of active tuberculosis were referred to the Chest Clinic for
      evaluation. RESULTS: Of 3828 persons evaluated, 20 had active tuberculosis, and
      33% of the screened cohort were tuberculin skin test positive. Of 466 persons
      with tuberculosis infection who were evaluated, only 55 persons were given
      isoniazid (INH), and only 20 completed preventive therapy. Most patients who were
      not given INH had taken it previously, were older than 35 years, or had
      continuing alcohol use which made physicians reluctant to prescribe isoniazid.
      CONCLUSION: Screening for tuberculosis may detect a significant number of cases
      of active disease when the background prevalence of the disease is very high.
      However, screening for infection as a means to prevent future cases is unlikely
      to be effective unless rates of administration and completion of isoniazid
      preventive therapy are increased.

PMID- 10206498
TI  - Longitudinal incidence of tuberculosis in South-East Asian refugees after re
      settlement.
AB  - SETTING: A State refugee screening programme in Victoria. OBJECTIVE: To determine
      the longitudinal incidence of tuberculosis (TB) in South-East Asian refugees in
      the first five years after re-settlement, and to determine predictors of risk.
      DESIGN: A retrospective cohort study of 1101 refugees from Laos, Cambodia and
      Vietnam screened for TB after arrival in Australia, in the 6-month period from
      July 1989 to January 1990. Incident cases of TB were identified by matching the
      refugee database with the TB notification database for 1989-1994, giving five
      years of follow-up data. Preventability was assessed for incident cases by
      reviewing medical records. MAIN OUTCOME: The development of active tuberculosis
      in the first five years after re-settlement. RESULTS: The incidence of active TB
      was 363/100000 during the first year after re-settlement, and 109/100000/year
      during the first five years. There were no incident cases of TB in refugees with
      initial skin test reactions <10 mm. Skin test reaction size was the only
      predictor of risk of TB. CONCLUSIONS: There is a high risk of tuberculosis in
      South-East Asian refugees, particularly in the first year after re-settlement.
      This risk decreases with time. Migration stress, concurrent illnesses and poor
      nutrition may be explanations for this observation. Refugees are at high risk for
      TB, even after pre- and post-migration screening, emphasising the importance of
      preventive therapy and follow up in this group.

PMID- 10206499
TI  - Trend in the annual risk of tuberculous infection in Egypt, 1950-1996.
AB  - OBJECTIVE: To determine the trend in the risk of tuberculous infection in non-BCG
      vaccinated children in Egypt in the period 1950-1996. METHODS: In 1949-1952, a
      tuberculin survey was carried out in Egypt by the World Health Organization (WHO)
      covering 103 districts. In 1995-1997 a tuberculin survey was carried in 73 620
      primary school children in grade one in the same districts, using international
      guidelines. The trend in tuberculous infection was determined by comparing the
      prevalence of Mantoux reactions of > or =6 mm in the two surveys in subjects
      without apparent BCG scar aged 6-7 years. For an estimate of current risk of
      infection the 17 mm cut-off point (number with 17 mm plus twice the number with
      greater than 17 mm) was used. RESULTS: In 1995-1997, 76% of children had a BCG
      scar. Infection prevalence estimates in 14 766 non-BCG-vaccinated children with a
      mean age of 6.7 years were 11.9%, 4.1%, and 2.1% for the cut-off points 6 mm, 10
      mm, and 17 mm, respectively. Decline in the risk of infection was estimated to be
      in the order of 50% over 45 years, or 1.5% per year. The geometric mean annual
      risk of infection in the 6.7 years before the survey was estimated at 0.32% (95%
      confidence interval 0.27-0.40%). For Egypt, the incidence of smear-positive
      tuberculosis was estimated at 16 per 100000 population, giving a case detection
      rate of 85% (range 56-100%). CONCLUSION: This survey has shown that the size of
      the tuberculosis problem in Egypt is considerably smaller now than it was 45
      years ago.

PMID- 10206500
TI  - Attitudes and knowledge of newly diagnosed tuberculosis patients regarding the
      disease, and factors affecting treatment compliance.
AB  - SETTING: An urban university teaching hospital. OBJECTIVES: To determine
      patients' attitudes to tuberculosis and their knowledge of the disease, and
      factors associated with treatment compliance. DESIGN: All adult patients
      commenced on treatment for tuberculosis from September 1994 to February 1996 were
      interviewed on initiation of treatment. To assess patient compliance with
      treatment, hospital clinical records were reviewed retrospectively. RESULTS: A
      total of 135 patients with a mean age (+/-SD) of 41.9 (+/-17.4) years (range 15
      84 years) were interviewed. The patients had limited understanding and knowledge
      about tuberculosis. There was a negative correlation between patient age and
      tuberculosis knowledge score (r = -0.18, P = 0.038). Patients with tertiary
      education had better knowledge than the others. Of 118 patients who were followed
      up in our chest clinic, 80 (67.8%) completed the prescribed treatment. Compliance
      with treatment and follow-up was not affected by age, sex, ethnic group,
      educational level, occupation, extent of knowledge, tuberculosis symptoms,
      hospitalisation for tuberculosis or duration of the prescribed treatment regimen.
      There was a trend toward poorer compliance among patients who equated
      disappearance of tuberculosis symptoms with cure of the disease. CONCLUSIONS:
      Malaysian patients with newly diagnosed tuberculosis attending a university
      teaching hospital had misconceptions and limited knowledge about the disease and
      its treatment. Educational background was an important determinant of a patient's
      level of knowledge about tuberculosis. Compliance was not affected by patient
      characteristics. Adequate counselling and education of patients and close
      relatives on tuberculosis and the necessity for prolonged treatment may help to
      improve treatment compliance.

PMID- 10206501
TI  - Progress in global tuberculosis control 1995-1996, with emphasis on 22 high
      incidence countries. Global Monitoring and Surveillance Project.
AB  - OBJECTIVE: To review global tuberculosis case notifications and treatment
      outcomes, and to assess progress in TB control 1995-1996, especially in the 22
      countries that carry 80% of all incident cases. DESIGN: Compilation of case
      notifications; cohort analysis of treatment outcomes in DOTS and non-DOTS
      programmes. RESULTS: The 181 of 212 countries (85%) that reported data to WHO in
      1997 covered 97% of the global population. They reported 3.81 million cases of
      tuberculosis, of which 1.29 million were smear-positive, representing case
      detection rates of approximately 39% and 51%, respectively. DOTS programmes
      diagnosed 67% of new pulmonary cases to be smear-positive (65% expected),
      compared with 30% in other control programmes. They evaluated a higher fraction
      of registered cases (94% vs 55%), achieved higher treatment success rates (78% vs
      45%), and a higher fraction of patients was shown to be cured by smear conversion
      (72% vs 23%). Despite the apparent advantages of DOTS, only 12% of all estimated
      cases, and only 15% of smear-positive cases, were treated in such programmes.
      CONCLUSION: With the exceptions of Vietnam, Peru and Tanzania, none of the 22
      highest-incidence countries achieved WHO targets for TB control. The slow
      progress is of greatest concern in 16 countries, including India, Indonesia,
      Nigeria and Pakistan.

PMID- 10206502
TI  - Self-assessment of tuberculin skin test reactions by drug users with or at risk
      for human immunodeficiency virus infection.
AB  - SETTING: Self-assessment of tuberculin test results, if accurate, could enhance
      tuberculosis screening efforts by reducing the need for follow-up visits for skin
      test reading. We investigated tuberculin test self-assessment in a longitudinal
      study of tuberculosis infection among drug users. OBJECTIVE: To determine the
      accuracy of tuberculin reaction self-assessment by drug users at high risk for
      tuberculosis infection. DESIGN: Two readings were compared of the same skin test,
      performed 48-72 hours after placement: 1) self-assessment using a simple yes-no
      approach to induration, versus 2) trained examiner reading. Self-assessments were
      performed immediately prior to trained examiner readings. RESULTS: Participants
      were 137 human immunodeficiency virus (HIV) seropositive and 344 HIV-seronegative
      current and former drug users. Ten per cent (35/344) of reactions read by
      participants as 'flat' were read by trained examiners as > or =5 mm (54% of which
      were > or =10 mm). Twenty-three per cent (19/82) of reactions read by trained
      examiners as > or =10 mm and 32% (35/110) of reactions read by trained examiners
      as being > or =5 mm were self-read by participants as 'flat'. Sensitivity (0.68)
      and specificity (0.83) of self-read tuberculin reactions were sub-optimal. Inter
      reader reliability was poorer between participants and trained examiners than
      between trained examiners. CONCLUSION: Self-assessments of tuberculin skin test
      responses by drug users with or at risk for HIV infection are not reliable.

PMID- 10206503
TI  - Tuberculin test variability: using the Norwegian Adrenaline-Pirquet method.
AB  - SETTING: Chest Unit, Bergen, Norway. OBJECTIVES: To study the agreement between
      two Adrenaline-Pirquet tuberculin tests and compare reactivity in groups read
      after 2, 3 and 4 days. DESIGN: Responders from a random sample of 1200 men and
      women 20-44 years of age in 1991 were tested with dual Adrenaline-Pirquet skin
      scratch tests with Norwegian-produced synthetic medium tuberculin and read after
      2-7 days. RESULTS: Of 588 subjects dually tuberculin tested, complete agreement
      existed in 220 (37.4%). A difference of 1 mm one way or the other was observed in
      239 (40.6%), whereas a difference of less than 3 mm was found in 567 (96.5%).
      Using the larger of the two reactions increased the rate of tuberculin positivity
      (> or =4 mm) by up to 8.4% compared with reading only one of the tests. No
      statistically significant differences were observed between subjects whose
      reactions were read after 2, 3 and 4 days. CONCLUSION: Under the non-blinded
      conditions of this study the dual Adrenaline-Pirquet tuberculin tests
      demonstrated reproducibility equivalent to the internationally recommended
      Mantoux test, and appeared to be independent of time of reading within four days.

PMID- 10206504
TI  - Risk factors for negative sputum acid-fast bacilli smears in pulmonary
      tuberculosis: results from Dakar, Senegal, a city with low HIV seroprevalence.
AB  - SETTING: Two teaching hospitals in Dakar, Senegal, a West African country with a
      low prevalence of human immunodeficiency virus (HIV) infection. OBJECTIVE: To
      determine whether patients with HIV-associated pulmonary tuberculosis have fewer
      acid-fast bacilli (AFB) in their sputum as assessed by routine microscopy, and to
      correlate the findings with systematically obtained clinical, radiographic and
      laboratory variables. DESIGN: Prospective study from November 1995 to October
      1996 of 450 consecutive patients diagnosed with pulmonary tuberculosis. RESULTS:
      Tuberculosis was diagnosed in 380 patients (84.4%) by positive bacteriology, in
      61 (13.6%) by a favorable response to anti-tuberculosis chemotherapy, and in nine
      (2.0%) by the presence of a miliary radiographic pattern. Forty (8.9%) patients
      were HIV-seropositive. AFB-negative smears were found in 14/40 (35.0%) of the HIV
      seropositive patients with pulmonary tuberculosis compared with 71/410 (17.3%) of
      the seronegative patients (risk ratio [RR] = 2.02, 95% confidence interval [CI]
      1.26-3.24, P = 0.01). Multivariate analysis revealed that AFB smear negativity
      was associated with absence of cavitation (P = 0.002), lack of cough (P = 0.005),
      the presence of HIV seropositivity (P = 0.02), a CD4+ cell count above 200/mm3 (P
      = 0.02), and age over 40 years (P = 0.03). CONCLUSIONS: Compared with HIV
      seronegative patients with pulmonary tuberculosis, seropositive patients in
      Dakar, Senegal, are more likely to have negative sputum-AFB smears. This
      phenomenon has now been observed in seven of eight sub-Saharan African countries
      with varying HIV seroprevalence from which reports are available.

PMID- 10206505
TI  - Predictors for multidrug-resistant tuberculosis among HIV-infected patients and
      response to specific drug regimens. Terry Beirn Community Programs for Clinical
      Research on AIDS (CPCRA) and the AIDS Clinical Trials Group (ACTG), National
      Institutes for Health.
AB  - SETTING: Mortality associated with human immunodeficiency virus (HIV) related
      multidrug-resistant tuberculosis (MDR-TB) is reduced with effective early
      therapy. Identifying predictors of, and effective regimens for, MDR-TB is
      critical. OBJECTIVE: A multicenter prospective study was initiated to 1)
      determine the demographic, behavioral, clinical and geographic risk factors
      associated with the occurrence of MDR-TB among HIV-infected patients, and 2) to
      evaluate the overall survival and clinical response of MDR-TB patients treated
      with specific drug regimens. METHODS: Patients were prospectively evaluated for
      MDR-TB. Information included history of prior treatment for tuberculosis, close
      contact with a known case of MDR-TB, and residence in a facility with known or
      suspected MDR-TB transmission. Patients with known MDR-TB, or those suspected to
      be at high risk, were offered enrollment in a treatment pilot study. Study drugs
      included levofloxacin and at least two additional drugs to which the patient's
      isolate was known, or most likely, to be susceptible. Survival was the primary
      endpoint. RESULTS: Complete data are available for 156 HIV-infected patients with
      confirmed tuberculosis. Sixteen (10%) had MDR-TB. Only a history of prior
      tuberculosis treatment was associated with MDR-TB in multivariate analysis (OR =
      4.4, P < 0.02). Twelve patients with MDR-TB enrolled in the treatment pilot had a
      median CD4 cell count of 51/mm3. The cumulative probability of survival at one
      year was 75% (95% CI 50.5-99.5) and at 18 months, 65.6% (95% CI 38.1-93.1).
      Toxicity requiring discontinuation of medications occurred in two patients.
      CONCLUSIONS: A history of treatment for tuberculosis was the only predictor for
      MDR-TB in a cohort of HIV-infected patients with tuberculosis. In addition, this
      prospective study supports the results of prior retrospective studies that
      effective treatment impacts on mortality. Current second-line treatment,
      including high dose levofloxacin, appears to be reasonably well tolerated.

PMID- 10206506
TI  - Evaluation of Mycobacteria Growth Indicator Tube (MGIT) for drug susceptibility
      testing of Mycobacterium tuberculosis.
AB  - SETTING: Mycobacteria Supranational Reference Laboratory. OBJECTIVE: To evaluate
      the Mycobacteria Growth Indicator Tube (MGIT) method for drug susceptibility
      testing of Mycobacterium tuberculosis. DESIGN: One hundred and one clinical
      strains of M. tuberculosis were evaluated for their susceptibilities to isoniazid
      (INH), rifampicin (RIF), ethambutol (EMB) and streptomycin (SM) by MGIT and by
      the proportion method on Lowenstein-Jensen (L-J) medium. The concentrations of
      drugs in MGIT were: 0.1, 1.0, 3.5 and 0.8 microg/ml for INH, RIF, EMB and SM,
      respectively. RESULTS: The results for individual drugs showed a good
      correlation: the specificity was 100% for INH, RIF and EMB and 92% for SM; the
      sensitivity was 100%, 94.6%, 96.1% and 89.7% for INH, RIF, EMB and SM,
      respectively, and the accuracy values 1.0, 0.98, 0.99 and 0.91. CONCLUSION: The
      MGIT system appears to be a reliable and simple non-radiometric method for the
      drug susceptibility testing of M. tuberculosis.

PMID- 10206507
TI  - In vitro susceptibility of Mycobacterium kansasii to the difluorinated quinolone
      sparfloxacin using a broth microdilution and macrodilution MIC system.
AB  - OBJECTIVES: To study the minimum inhibitory concentrations (MIC) of the
      difluorinated quinolone sparfloxacin against 32 clinical isolates of
      Mycobacterium kansasii from 23 patients, all of whom had clinically significant
      infections due to M. kansasii, and 11 the acquired immune-deficiency syndrome
      (AIDS). To study the correlation between the microdilution and macrodilution
      techniques in M7H9 broth. DESIGN: The MICs were determined by two methods: broth
      microdilution in microplates and broth macrodilution in tubes. The isolates were
      inoculated into two-fold drug dilutions (ranging from 0.063 to 8 microg/ml) in
      Middlebrook 7H9 broth and then incubated at 37 degrees C for 21 days. RESULTS:
      All 32 strains were susceptible, with identical MIC results in both methods,
      96.9% of them showing an MIC of 0.25 microg/ml. CONCLUSION: These MIC studies
      suggest that sparfloxacin may be useful for drug treatment of slow-growing
      nontuberculous mycobacteria such as M. kansasii. The microdilution method appears
      to be a reliable method for routine susceptibility testing of M. kansasii, and is
      easy to interpret and to carry out.

PMID- 10206508
TI  - Application of a computer-directed automated microscope in mycobacteriology.
AB  - Microscopy is currently the fastest, cheapest and most easily performed technique
      in mycobacteriology; it can be used in any laboratory. However, the sensitivity
      of microscopy is unsatisfactory and it is time-consuming. To eliminate these
      drawbacks, we have constructed a computer-directed automated microscope. To
      evaluate the equipment, we examined a total of 132 smears of sputum and 74 smears
      of liquid media. Manual microscopy was positive for 53 and negative for 79 sputum
      smears, while automated microscopy was positive for 55 and negative for 77 sputum
      smears. Both methods furnished 50 positive and 24 negative smears of liquid
      media. We conclude that the automated microscope is able to detect acid-fast
      bacteria, the examination procedure with the instrument is more rapid (1.8-3.5
      min/slide) and it is always possible to follow the standard recommendations of
      microscopy.

PMID- 10206509
TI  - Jabberwocky.

PMID- 10206510
TI  - DOTS with a SMILE.

PMID- 10206511
TI  - Sequential infection with two different environmental mycobacteria in a 50-year
      old HIV-negative man.

PMID- 10206512
TI  - Tuberculosis pure red cell aplasia.

PMID- 10206513
TI  - Viability of mycobacteria in formalin-fixed tissues.

PMID- 10206514
TI  - The relationship between the uncomfortable loudness level and the acoustic reflex
      threshold for pure tones in normally-hearing and impaired listeners--a meta
      analysis.
AB  - The objective of this study was to determine the potential of the acoustic reflex
      threshold (ART) as a predictor of the uncomfortable level (ULL) and to identify
      related areas for investigations in the future. Eleven studies reporting data
      from 141 normally-hearing and 240 impaired hearing subjects have been reviewed,
      focusing on methods, test conditions and subjects. Results and conclusions are
      discussed and new calculations have been performed on the reported data. The
      median difference between ART and ULL across studies and frequencies was 5 dB
      both in normally-hearing and impaired subjects. Some authors argue, that although
      a close relationship of mean values of the two measurements may exist, prediction
      of the ULL based on ART measurement will be inaccurate because of high inter
      subject variability. A statistically significant correlation exists between the
      mean HTL, the mean ART and the mean ULL in impaired hearing, while a relationship
      between the mean ART and the mean ULL does not exist in normal hearing. Based on
      pooled data across frequencies from the reviewed studies the mean ULL= (0.64 x
      mean ART+38) dB HL. The discrepancies between the results found in the reviewed
      studies may be explained by different instructions and stimulus presentation
      orders when assessing the ULL, difficulty in assessing the sound pressure level
      in the ear canal, influence of varying background noise levels and different
      admission criteria. It is recommended that the relationship between different
      loudness levels and the ART be investigated in normally-hearing subjects and in
      subjects with different levels of impairment, using standardized instructions. To
      further provide uniformity of the test material groups should be selected
      according to history of middle ear diseases and the use of hearing aids.

PMID- 10206515
TI  - Optimal band pass filtering of transient evoked otoacoustic emissions in
      neonates.
AB  - This paper investigated the performance of an optimal bandpass filtering
      technique to effectively identify click evoked otoacoustic emissions in neonates.
      The frequency response of the filter was optimized by maximizing the correlation
      coefficient between two replicate recordings (reproducibility). The optimal cut
      off frequencies were also set by controlling the maximum energy loss after
      filtering to stop the crucial response contents being filtered along with the
      noise. As an additional constraint, the cut-off frequencies were forced to be
      outside the range of 1.6 to 4.2 kHz to avoid (in a response identification task)
      the spontaneous otoacoustic emissions from polarizing the cut-offs and thereby
      filtering fundamental frequency components, thus leading to an erroneous response
      classification. The best performance of the optimal filter in terms of increasing
      the post-filtering reproducibility was obtained when the procedure was applied to
      recordings whose reproducibility before filtering ranged between 60 and 80 per
      cent, i.e. for responses classified in most cases as partial pass.

PMID- 10206516
TI  - A longitudinal study of the validity of parental reporting in the detection of
      otitis media and related hearing impairment in infancy.
AB  - A total of 150 full-term and 66 pre-term infants were selected at birth and
      prospectively examined at three-monthly intervals from birth until the age of 27
      months. Parental reports of middle ear infection and/or hearing impairment were
      obtained prior to otoscopic and audiometric evaluation. The relationships between
      parental reports and the diagnoses acute otitis media (AOM), otitis media with
      effusion (OME) and hearing impairment (HI), were assessed in terms of
      sensitivity, specificity and positive and negative predictive values, using the
      data obtained during the follow-up period. AOM and OME were diagnosed using
      otoscopy and tympanometry. Hearing was assessed by conditioned orientation reflex
      audiometry. HI was defined as averaged thresholds > or = 20 dB compared with age
      appropriate response levels. Despite the repeated feedback which parents received
      on the middle ear condition and hearing of their infants, the majority fail to
      recognize the presence of AOM, OME and HI. The limited sensitivity of parental
      reporting should discourage both researchers and clinicians from using it as a
      diagnostic or monitoring instrument, but they should not disregard parental
      concern when confronted with it.

PMID- 10206518
TI  - Speech intelligibility in noisy environments with one- and two-microphone hearing
      aids.
AB  - In this study speech intelligibility in background noise was evaluated with 10
      binaural hearing-aid users for hearing aids with one omnidirectional microphone
      and a hearing aid with a two-microphone configuration (enabling an
      omnidirectional as well as a directional mode). Signal-to-noise ratio (SNR)
      measurements were carried out for three different types of background noise
      (speech-weighted noise, traffic noise and restaurant noise) and two kinds of
      speech material (bisyllabic word lists and sentences). The average SNR
      improvement of the directional microphone configuration relative to the
      omnidirectional one was 3.4 dB for noise presented from 90 degrees azimuth. This
      improvement was independent of the specific type of noise and speech material,
      indicating that one speech-in-noise condition may yield enough relevant
      information in the evaluation of directional microphones and speech understanding
      in noise.

PMID- 10206517
TI  - Sound localization for a virtual sound source in cases of chronic otitis media.
AB  - Sound localization in subjects with chronic otitis media (COM) was examined
      before and soon after ear surgery by means of virtual sound presented by
      headphones, sound being synthesized based on the head-related transfer functions
      (HRTFs) in a normal subject. The localization ability in COM patients was usually
      worse than that in normal subjects, but was better than expected when compared
      with cases of acute loss. On the other hand, the effects of hearing improvement
      on localization ability observed in COM patients were smaller than those of
      simulated acute hearing loss achieved by earplugs in normal subjects. This seems
      to suggest that the localization cues in patients with chronic hearing loss are
      different from those under normal conditions.

PMID- 10206519
TI  - Clinical evaluation of a full-digital in-the-ear hearing instrument.
AB  - In this study we measured the efficacy of a digital hearing aid with compression
      and noise reduction in a well-controlled clinical field trial in two independent
      centres. The experiments focused on a number of aspects of the application of the
      digital hearing aids. The study combines a field test of 2x4 weeks with
      laboratory experiments. We used objective measurements (speech perception tests
      in background noise, loudness scaling) and subjective assessments
      (questionnaires). The measurements were performed before and after the field
      test. The questionnaires were collected after each field test. The results of the
      digital hearing aids were compared to the results of similar tests with newly
      fitted analogue reference aids. The study involved 27 sensorineural hearing
      impaired subjects, wearing new hearing aids. They comprised a representative
      sample of in-the-ear users. We used a crossover design in which the subjects used
      successively digital hearing aids and analogue reference aids in a randomized
      order. On average, the subjective data are more positive than the objective data.
      In the end, 20 out of 27 subjects had an overall preference for the digital
      hearing aid. The financial implications were not taken into consideration.
      However, objective data do not support this strong subjective preference. A
      reason could be that the method of analysis (short sentences in a short-duration
      background noise) is not suited for the digital hearing aid; the testing
      procedure does not allow the noise-reduction algorithm to adapt to the background
      noise. There was a striking difference between the results for the two centres.
      This difference can, to at least a certain extent, be attributed to the timing of
      speech relative to the background noise in the objective tests. This illustrates
      that the test conditions are critical in modern non-linear signal-processing
      hearing aids with long time constants. New evaluation techniques should be
      developed for this new generation of active non-linear hearing aids.

PMID- 10206521
TI  - European Consensus Statement on Neonatal Hearing Screening.

PMID- 10206520
TI  - Predictors of cochlear implant performance.
AB  - Open set speech understanding with cochlear implants, without speechreading, is
      nowadays a common finding. However, there is a large variation in speech
      understanding between cochlear implant users. We tried to find pre-operative
      parameters which predicted the post-operative results. Thirty-seven adult post
      lingually deafened Nucleus cochlear implant users with a mean age of 46 years
      (range 16 68) and a mean duration of deafness of 15 years (range 1.5-47) were
      studied. Pre-operatively, we performed pure-tone audiometry, round window and ear
      canal electrical stimulation, psychological tests and imaging. Additionally, we
      measured pre-operatively speech understanding in the auditory, the visual and the
      audiovisual conditions with several tests which were also administered after 6
      and 12 months' implant experience. Correlation analysis between the pre-operative
      variables and the post-operative factors showed that duration of deafness and
      residual hearing are the most important predictors. The temporal difference limen
      in pre-operative round window electrical stimulation is a secondary predictor.

PMID- 10206522
TI  - Childhood medulloblastoma: progress and future challenges.
AB  - Medulloblastoma and other primitive neuroectodermal tumors are the most common
      malignant tumors of childhood. Progress has been slowly made in the management of
      such tumors. Long-term neurocognitive sequelae of treatment in children with
      medulloblastoma are common and recent treatment trials have attempted to reduce
      the amount of craniospinal radiation therapy or delay radiation therapy in
      attempts to reduce such sequelae. Surgery remains a critical component of
      treatment, although there is increasing concern about surgically-related
      complications, including the cerebellar mutism syndrome. For older children,
      craniospinal radiation remains an integral part of management. However, recent
      studies have suggested an excellent outcome after reduced-dose craniospinal
      radiation therapy and adjuvant chemotherapy. The role of chemotherapy is
      expanding for children with medulloblastoma and is now presently a component of
      protocols for children with average-risk and poor-risk disease. For children with
      poor-risk disease, intensifications of chemotherapy both during and after
      radiation therapy are presently being explored. Treatment of infants and young
      children with medulloblastoma remains problematic and a variety of different
      approaches are being investigated with the aims of both improving outcome and
      reducing long-term sequelae.

PMID- 10206523
TI  - Reversible disability associated with epilepsy.
AB  - Epilepsy is a syndrome complex in which the impairments include seizures,
      cognitive arrest and regression, psychiatric illness, and motor and visual
      disorders. In both lesional and non-lesional epilepsy there is evidence of
      reversibility of these impairments in some patients which provides compelling
      evidence that there is a dynamic pathogenetic mechanism which can 'take-out'
      discreet or global cortical functions. The best evidence that we have suggests
      that seizures themselves particularly sub-clinical seizure activity are the major
      factor. Numerous examples of partial and even complete recoveries as a result of
      medical and surgical treatments are now available. These support the notion that
      in addition to direct seizure activity there is a pervasive element to the
      syndromes of epilepsy which causes anything from mild attention deficit or
      difficulties with language processing to catastrophic loss of cognitive and
      social functioning. The malignant seizure syndromes are mostly defined by the
      high risk of these impairments. The challenge of the developmental epilepsies is
      to explore the pathogenesis and develop new treatments. Perhaps the most
      difficult aspect of this work is to understand the critical periods for recovery
      and thus how to avoid irreparable damage.

PMID- 10206524
TI  - Deletion analysis in Turkish patients with spinal muscular atrophy.
AB  - Childhood proximal spinal muscular atrophy (SMA) is an autosomal recessive
      disorder which presents as a severe, intermediate or mild condition. Here we
      present the molecular analysis of SMA candidate genes, the survival motor neuron
      gene (SMN), the neuronal apoptosis inhibitory protein gene (NAIP) and the p44
      gene. Deletion frequency rate of these candidate genes is 93% in 106 Turkish SMA
      patients. Various deletion haplotypes by using genotypes of SMN, NAIP and p44
      genes are constructed. Haplotype A, which is the deletion of all three involved
      genes, was found only in the most severe group with an early onset of usually
      less than 2 months of age.

PMID- 10206525
TI  - Landau-Kleffner syndrome (LKS): long-term follow-up and links with electrical
      status epilepticus during sleep (ESES).
AB  - We describe 11 patients affected by Landau-Kleffner syndrome (LKS) with a mean
      follow-up of 9 years and 8 months. EEG recordings during wakefulness, NREM and
      REM sleep showed a bitemporal electrical status epilepticus during sleep (BTESES)
      in all cases; four of them presented a shift from a BTESES towards an
      'intercalated electrical status epilepticus during sleep' (IESES) accompanied by
      a global regression of cognitive and behavioural functions in 3/4 of cases. At
      the last observation, only 18.2% of cases presented a complete language recovery
      and mental retardation was evident in 63.6%. The prognosis of LKS in our cases
      may depend on the interaction of different negative factors such as onset of
      aphasia before 4 years, its duration for longer than 1 year, long-lasting
      duration and continuity without fluctuations of BTESES/IESES, probably
      preexisting mild speech delay. It is important for the prognosis to utilize
      antiepileptic treatment and possibly neurosurgical techniques to eliminate EEG
      paroxysmal abnormalities. At present, no similar cases with clinical-EEG
      evolution from LKS to electrical status epilepticus during sleep (ESES) have ever
      been described. Our observation demonstrates that LKS and ESES classified as
      different clinical-EEG syndromes represent two aspects of the same brain
      dysfunction and they may exist separately or pass one into the other with a
      change in the clinical-EEG picture. The common origin of the two syndromes is
      confirmed by recent functional brain imaging, neurophysiological and
      neurosurgical techniques.

PMID- 10206526
TI  - Normative data of sympathetic skin response and RR interval variation in Turkish
      children.
AB  - Sympathetic skin response (SSR) and RR interval variation (RRIV) are used
      commonly for the assessment of sympathetic and parasympathetic nervous system
      function, respectively. We determined the normal values of SSR and RRIV in 23 (14
      females, nine males) Turkish children aged 5 to 14 (mean 9.86, SD 2.48) years.
      SSR was recorded on the hands and feet during the electrical stimulation of both
      median and posterior tibial nerves, respectively. Similar response was elicited
      on both feet during the stimulation of the right median nerve. RRIV testing was
      performed during rest on the supine position and deep inspiration at a frequency
      of 6 times/min. The SSR was elicited in all children. The mean SSR latencies
      recorded on the feet during the stimulation of median or posterior tibial nerve
      were significantly more prolonged than those recorded at the hands (P < 0.001).
      There was no significant difference between the mean latencies of SSR recorded at
      the ipsilateral and contralateral palms or soles. The mean latencies recorded at
      the sole during stimulation of the median nerve were not significantly different
      compared to those that recorded at the sole during the posterior tibial nerve (P
      > 0.05). The SSR amplitudes were not assessed because of great variability and
      rapid habituation. The mean RRIV (46.54+/-11.29%) during deep breathing was
      significantly increased as compared to that (35.90+/-10.63%) during rest (P <
      0.003). As a result, SSR and RRIV are preferred non-invasive tests for evaluation
      of autonomic nervous system in children. The SSR is useful and reliable if it is
      obtained in the optimum technical conditions. Further research is necessary to
      establish strict criteria for abnormality.

PMID- 10206527
TI  - Excessive water drinking behavior in autism.
AB  - The aim of this study was to determine the incidence of polydipsia in 49 autistic
      children, and also the influence of psychotropic drugs and residential factors on
      water drinking behavior, as compared with in 89 mentally retarded children, in
      schools for mentally handicapped children in Fukui prefecture. Questionnaires
      were used to detect polydipsia and to assess the severity of the water drinking
      behavior in the autistic children and mentally retarded children. The incidence
      of polydipsia in the autistic children tended to be higher (P = 0.074) than that
      in the retarded children. The severity of water drinking behavior was
      significantly higher in autism (P = 0.022) than in mental retardation. The
      majority of the autistic children with polydipsia had been taking no psychotropic
      drugs. The incidence of polydipsia showed no significant difference between two
      residential situations, i.e. 'not at home' and 'at home'. The present study
      suggests that polydipsia or excessive water drinking behavior occurs more often
      in autism than in mental retardation, possibly due to some intrinsic factor in
      autism itself.

PMID- 10206528
TI  - Tc-99m HMPAO brain perfusion imaging in young Down's syndrome patients.
AB  - Down's syndrome (DS) is characterized by moderate mental retardation and a
      variety of abnormalities involving multiple organ systems. There is a high
      incidence of Alzheimer's disease (AD) type dementia beyond the age of 35. In this
      study, single photon emission computed tomography (SPECT) brain perfusion imaging
      of young Down's syndrome patients was performed to define the perfusion pattern.
      Tc-99m HMPAO brain perfusion SPECT was performed on 17 young DS patients, aged 3
      24 years (mean: 10.9+/-5.9 years). None of the patients had dementia symptoms.
      Brain perfusion scans were acquired 15 min after i.v. injection of 12 MBq/kg of
      Tc-99m HMPAO using a single head rotating gamma camera. Images were analyzed
      visually and semiquantitatively by defining side-to-side asymmetry index. Nine DS
      cases showed normal brain perfusion. Eight of the 17 cases revealed mostly
      unilateral parieto-temporal, parieto-occipital and frontal hypoperfusions. The
      side-to-side asymmetry indices for these visually interpreted regional brain
      perfusion abnormalities ranged from 6 to 15%. These findings revealing mostly
      unilateral parieto-temporal and frontal hypoperfusions may not be considered as
      predictive patterns of dementia related Alzheimer type perfusion deficits in DS.
      However, such findings may connect to other functional imaging studies related to
      the higher cortical dysfunction in mental retardation.

PMID- 10206529
TI  - Helicobacter pylori seropositivity in patients with severe neurologic impairment.
AB  - The objective of this study was to assess the prevalence of Helicobacter pylori
      seropositivity in institutionalized patients with severe neurologic impairment.
      Anti-H. pylori immunoglobulin G antibody in serum was measured in 196
      institutionalized Japanese patients using enzyme linked immunosorbent assay,
      taking an antibody level >50 units/ml as evidence of H. pylori seropositivity.
      Patient age pattern and duration of institutionalization were examined for the
      relationships with H. pylori seropositivity. We also examined for seroconversion
      indicating new H. pylori infection in initially negative patients 1 year later.
      Positivity for H pylori infection among institutionalized patients was also
      compared with positivity among patients living at home. H. pylori seropositivity
      was present in 81.1% of subjects. Prevalence of H. pylori seropositivity
      increased with both age and duration of institutionalization. The serum level of
      anti-H. pylori immunoglobulin G antibody in patients over 20 years old was
      consistently high, approximately twice that of subjects less than 10 years of
      age. Of 38 patients initially negative for H. pylori infection, 18 (47.4%) had
      become positive at 1 year. H. pylori seropositivity was significantly more
      prevalent among institutionalized patients than among patients living at home (P
      < 0.0001). This study confirms that high H. pylori seropositivity rates are found
      among institutionalized patients with severe neurologic impairment. Our
      observations suggest person to person transmission, with fecal to oral, salivary
      secretion and respiratory droplet routes possibly being important pathways.

PMID- 10206530
TI  - The effects of stimulus rates on the amplitude of median nerve somatosensory
      evoked potentials: the developmental change.
AB  - We examined the effects of stimulus rates on the somatosensory evoked potential
      (SEP) amplitudes following median nerve stimulation at the wrist in 42 children.
      We divided these subjects into five groups according to their age (0-6 months, 7
      12 months, 1-3 years, 4-6 years and more than 7 years) and measured the peak-to
      peak amplitude of every component (N9, P10, N11, P13/14, N18, N20, P23, N30) at
      stimulus rates of 1.0, 3.5 and 5.5 Hz. From N9 to N18, there was no significant
      change in amplitude nor latency with stimulus rate change in all groups. The
      amplitude attenuation was found at the N20 and N30 peaks in the young group (0
      months to 3 years) and at P23 in all groups with an increasing stimulus rate. The
      attenuation rate of P23 amplitude was influenced by the age of subjects, being
      greater in younger groups and greatest in the youngest group (0-6 months). The
      differences of amplitude attenuation rate between this group and the rest were
      statistically significant. The results of this study indicate that the amplitudes
      of the cortical components of SEP in children are greatly influenced by the
      stimulus rate. Thus when we discuss the amplitude of cortical waves in childhood,
      we should also pay attention to the stimulus rates.

PMID- 10206531
TI  - Tremor and seizures associated with chronic manganese intoxication.
AB  - Tremor and seizures developed in a 2-year-old girl receiving total parenteral
      nutrition. T1-weighted images on MRI revealed areas of hyperintensity in the
      basal ganglia, brainstem and cerebellum. Blood manganese was elevated. The
      symptoms and MRI abnormalities disappeared after withdrawal of manganese
      administration. The recommendation of daily parenteral manganese intake was
      discussed.

PMID- 10206532
TI  - Modified functional hemispherectomy in hemimegalencephaly.
AB  - We report a case of hemimegalencephaly in a 13-month-old girl successfully
      treated with modified functional hemispherectomy. Instead of total temporal
      lobectomy, medial temporal lobectomy with excision of the hippocampus and
      amygdala was carried out. The central region including the parasagittal tissue
      was preserved. A few days after the surgery seizures completely ceased.
      Administration of anticonvulsants was stopped 5 months after the surgery, and she
      has been seizure-free for 42 months.

PMID- 10206533
TI  - The origin of hypsarrhythmia and tonic spasms in West syndrome: evidence from a
      case of porencephaly and hydrocephalus with focal hypsarrhythmia.
AB  - We report on a 3-year-old girl with West syndrome and with focal hypsarrhythmia.
      The left hemisphere of the patient was virtually completely defective and
      continuous hypsarrhythmia was only seen in the residual right frontal cortex,
      where an interictal single photon emission computed tomography (SPECT) showed
      hyperperfusion. Despite a focal epileptic pattern, the tonic spasms were quite
      symmetrical. In our patient, spasms might not require the sensorimotor cortex,
      but the brainstem containing the descending pathways that control spinal reflexes
      and other infratentorial structures seem to be essential for the occurrence of
      spasms. This is in accordance with the result of an ictal SPECT that showed
      hyperperfusion of the brainstem and cerebellum. These findings suggest that
      hypsarrhythmia originates from cortical lesions, while subcortical structures may
      be primarily responsible for the tonic spasms in this patient.

PMID- 10206534
TI  - Hemiballismus associated with Influenza A infection.
AB  - A case of 2-year and 3-month-old boy developing right hemiballismus and transient
      selective unilateral involvement in the left thalamus on MRI during Influenza A
      infection is reported. Hemiballismus is an extremely rare neurological
      complication and, to our knowledge, this is the first case showing hemiballismus
      during Influenza A infection.

PMID- 10206535
TI  - Moyamoya disease: long term follow-up including a normal pregnancy.
AB  - We present a woman with moyamoya disease. The patient was born by prolonged
      vaginal delivery after a long pregnancy lasting 43 weeks. During her first years
      of life she depicted poor psychomotor development. When she was 9 years old a
      diagnosis of moyamoya disease was made. Annual neurologic evaluations have
      revealed moderate motor deficiency, slurred speech and borderline mental
      capacity. At 26 years of age she became pregnant and was prophylactically treated
      with 40 mg/day oral nicardipine. She had a healthy child after an uncomplicated
      40 week pregnancy. When she was 33 years old a magnetic resonance (MR) study
      disclosed a zone of ischemic parenchyma. MR angiography yielded results similar
      to those of conventional arteriography. At present, the patient is 36 years old,
      lives a normal life and works in a factory.

PMID- 10206536
TI  - The similarity and homogeneity in acute necrotizing encephalopathy: acute
      cerebral necrotizing syndrome.

PMID- 10206537
TI  - Remarkable improvement of severe diffuse axonal injury without L-dopa treatment.

PMID- 10206538
TI  - Cytotoxic effects of NSL-1406, a new thienopyrimidine derivative, on leukocytes
      and osteoclasts.
AB  - We synthesized a series of thienopyrimidine derivatives and examined their
      cytotoxic effects on several cell lines. One of the derivatives, NSL-1406, was
      shown to exert potent cytotoxic effects on leukemia cell line including P388
      cells and J774 cells. It was also inhibitory on mouse osteoclasts and suppressed
      the in vitro bone resorption by osteoclasts at nanomolar concentrations.

PMID- 10206539
TI  - A new class of anti-HIV agents: synthesis and activity of conjugates of HIV
      protease inhibitors with a reverse transcriptase inhibitor.
AB  - Conjugates of HIV protease inhibitors with a reverse transcriptase inhibitor were
      synthesized, which expressed excellent antiviral activity compared with that of
      the individual components. The remarkable antiviral activity of the conjugated
      compounds may be due to their penetration into the cell and later splitting into
      two different classes of anti-HIV agents.

PMID- 10206541
TI  - Piperidinyl-3-phosphinic acids as novel uptake inhibitors of the neurotransmitter
      gamma-aminobutyric acid (GABA).
AB  - Piperidinyl-3-phosphinic acid 2, piperidinyl-3-methylphosphinic acid 3 and N-(4,4
      diphenyl-3-butenyl)piperidinyl-3-phosphinic acid 4 have been synthesized as
      bioisosteres of the corresponding amino carboxylic acids, which are potent and
      specific GABA-uptake inhibitors. The novel amino phosphinic acids were tested for
      their GABA-uptake inhibitory activity and 2 and 4 were identified as the first
      phosphinic acid based GABA-uptake inhibitors. The methylphosphinic acid 3 was
      found to be inactive.

PMID- 10206540
TI  - Syntheses of two trimannose analogs each containing C-mannosyl or 5-thio-C
      mannosyl residue: their affinities to concanavalin A.
AB  - C-Mannosyl residue-containing trimannose ManC alpha(1,6)[Man alpha(1,3)Man] (2)
      and 5-thio-C mannosyl residue-containing trimannose 5SManC alpha(1,6)[Man
      alpha(1,3)Man] (3) were synthesized via a glycosyl radical addition to enone
      derivative of mannose (6). Dissociation constants for the binding of these
      trisaccharides to concanavalin A (ConA) were determined by a fluorescence
      anisotropy inhibition assay: Kd = 198 and 31 microM, respectively. The
      unexpectedly large Kd value for the compound 2 compared with the compound 3 and
      the natural trimannose 1 demonstrates a characteristic of C-glycoside.

PMID- 10206542
TI  - Benzenesulfonamide derivatives of 2-substituted 4H-3,1-benzoxazin-4-ones and
      benzthiazin-4-ones as inhibitors of complement C1r protease.
AB  - A series of 2-sulfonyl-4H-3,1-benzoxazinones was prepared that inhibit C1r
      protease in vitro. Several compounds were found to be selective for C1r verses
      the related serine protease trypsin. Selected compounds demonstrated functional
      activity in a hemolysis assay.

PMID- 10206543
TI  - Synthesis, in vitro cytotoxicity and in vivo anti-inflammatory activity of long
      chain 3-amino-1,2-diols.
AB  - The synthesis of long chain 3-amino-1,2-diols was carried out based on Sharpless
      asymmetric epoxidation of long chain allylic alcohols and regioselective
      nucleophilic ring opening by azido group. The in vitro cytotoxicity of the
      compounds prepared was evaluated against six solid tumor cell lines (A2780, H322,
      LL, WiDr, C26-10, UMSCC-22B). Free 3-amino-1,2-diols exhibited IC50 values
      between 1.45 microM and 32 microM. These compounds also presented interesting
      inhibition of carrageenin-induced paw edema in rats (85.3% - 79.6% at a
      concentration of 0.15 mmol/kg).

PMID- 10206544
TI  - Synthesis of novel 4'-C-methyl-pyrimidine nucleosides and their biological
      activities.
AB  - Two novel 4'-C-methylnucleosides, 4'-methylBVDU 9 and 4'-methylBVaraU 10, were
      synthesized. The former was derived from 3',5'-di-O-acetyl-2'-deoxy-4'-C
      methyluridine 12, and the latter was produced via glycosylation between 4-C
      methyl-D-ribose derivative 11 and a silylated bromovinyl uracil. 4'-MethylBVDU 9
      exhibited particularly potent anti-varicella-zoster virus (VZV) activity in
      vitro.

PMID- 10206545
TI  - Ring constrained analogues of the orvinols: the furanomorphides.
AB  - A series of furanomorphides were synthesised as ring-constrained analogues of
      buprenorphine and related orvinols. Evaluation in binding and functional assays
      has shown that the furanomorphides have reduced efficacy at the mu opioid
      receptor compared to the orvinols.

PMID- 10206547
TI  - Enantio- and diastereocontrolled dopamine D1, D2, D3 and D4 receptor binding of N
      (3-pyrrolidinylmethyl)benzamides synthesized from aspartic acid.
AB  - Subreceptor selectivity tuning of N-(3-pyrrolidinyl)benzamides leading to the
      selective dopamine D3 ligand ent1h and the derivatives 1g and 1e/ent1e which
      preferably recognize human D2 or D4 receptors, respectively, is described.
      Binding profiles were controlled by both, absolute and relative configuration.
      The enantiopure target compounds were synthesized from aspartic acid.

PMID- 10206546
TI  - Potent and selective bicyclic lactam inhibitors of thrombin: Part 3: P1'
      modifications.
AB  - The synthesis and antithrombotic activity of a series of nonpeptide bicyclic
      thrombin inhibitors are described. We have explored the SAR around the P1' site.
      Modification of the P1' site has been found to affect potency and selectivity.

PMID- 10206548
TI  - Novel reverse-turn mimics inhibit farnesyl transferase.
AB  - Reverse-turn inducing bicyclic lactams were incorporated into the substrate
      sequence recognized by farnesyl transferase to create inhibitors of RAS
      farnesylation. While the free peptides did not show any effect on the
      farnesylation, their Fmoc-protected counterparts impede the transformation of RAS
      with IC50's in the low micromolar range.

PMID- 10206549
TI  - Synthesis and activity of gamma-(L-gamma-azaglutamyl)-S-(p-bromobenzyl)-L
      cysteinylglycine: a metabolically stable inhibitor of glyoxalase I.
AB  - The inhibition of glyoxalase I enzyme to increase cellular levels of
      methylglyoxal has been developed as a rationale for the production of anticancer
      agents. Synthesis of a peptidomimetic analog of the previously prepared potent
      glyoxalase inhibitor, S-(p-bromobenzyl)glutathione (PBBG), was accomplished by
      inserting a urea linkage, NH-CO-NH, to replace the gamma-glutamyl peptide bond.
      Thus, the target compound, gamma-(L-gamma-azaglutamyl)-S-(p-bromobenzyl)-L
      cysteinylglycine 6, was a potent inhibitor of glyoxalase I with almost no loss of
      activity when compared to PBBG. However, unlike PBBG, 6 was completely resistant
      to enzymatic degradation by kidney homogenate or by purified gamma
      glutamyltranspeptidase enzyme.

PMID- 10206550
TI  - Bicyclo[3.2.1]octanes: synthesis and inhibition of binding at the dopamine and
      serotonin transporters.
AB  - Herein we report the synthesis of a series of bicyclo[3.2.1]octanes and their
      binding characteristics at the dopamine and serotonin transporters. The data
      confirm that a heteroatom at position 8 of the tropane nucleus is not a
      prerequisite for binding since the bicyclo[3.2.1]octanes prove potent inhibitors
      of both transporters. Therefore the three-dimensional topology of the ligand may
      be more important than specific functionality with respect to stereospecific
      binding at the acceptor site.

PMID- 10206551
TI  - Nonpeptide glycoprotein IIB/IIIA inhibitors. 19. A new design paradigm employing
      linearly minimized, centrally constrained, exosite inhibitors.
AB  - A new series of potent, linearly-minimized, orally active, selective GPIIb/IIIa
      inhibitors is identified. Thus 15 (L-750,034) achieves interaction via a
      constrained, non-turned conformation that maintains the proper distance between
      its charged termini and full sulfonamide exosite interaction. The diminutive
      stature and the proposed linear conformation of L-750,034 define a new paradigm
      for the conceptualization of RGD mimics.

PMID- 10206552
TI  - Synthesis and hypoglycemic effect of chrysin derivatives.
AB  - A series of 18 chrysin derivatives, prepared by alkylation and condensation, were
      fully characterized by NMR and other techniques and tested in vivo against the
      diabetes mellitus. Several modified compounds especially those with propyl,
      butyl, octyl and tolyl groups were found to have hypoglycemic effect on diabetec
      mice in spite of the fact that chrysin itself had inhibited insulin release by 40
      60%. None of the test animals died at the maximum dose 500mg/kg and did not cause
      any significant change in general feature, water and food consumption, body
      weight and organ weight when we examined the acute oral toxicity of those
      compounds having significant hypoglycemic effect.

PMID- 10206554
TI  - Polymer-bound N-hydroxysuccinimide esters: a column-free fluorescent-labeling
      method.
AB  - Polymer-bound N-hydroxysuccinimide esters of 1-pyrenebutyric acid, 6
      carboxyfluorescein diacetate, and biotin were efficiently prepared. Column-free
      fluorescent- and biotin-labeling reactions of various amines using these resins
      were successfully demonstrated.

PMID- 10206553
TI  - Combined NK1 and NK2 tachykinin receptor antagonists: synthesis and structure
      activity relationships of novel oxazolidine analogues.
AB  - We report herein the synthesis and structure-activity relationships of a series
      of novel oxazolidine analogues with regards to NK1 and NK2 tachykinin receptor
      binding affinity. Among this series of oxazolidine analogues, some compounds
      exhibited excellent high binding affinities for both NK1 and NK2 receptors. In
      addition, we describe the inhibitory effect in vivo on SP-induced airway vascular
      hyperpermeability and NKA-induced bronchoconstriction in guinea pigs.

PMID- 10206555
TI  - Biophysical and biochemical properties of oligodeoxy-nucleotides containing 4'-C-
      and 5'-C-substituted thymidines.
AB  - We have previously reported oligodeoxynucleotides (ODNs) containing 4'-C- and 5'
      C-substituted thymidines, which demonstrated certain favorable biophysical and
      biochemical properties. In this communication, the hybridization and nuclease
      stability data of the ODNs along with their capability to induce RNase H activity
      are presented.

PMID- 10206556
TI  - Phosphorothioate oligodeoxyribonucleotides inhibit ribonuclease L thereby
      disabling a mechanism of interferon action.
AB  - Phosphorothioate oligodeoxyribonucleotides were found to be inhibitors of the 2
      5A-dependent RNase L. Inhibitory potency depended upon the chain length of the
      phosphorothioate oligonucleotide and was dependent on the phosphorothioate
      substitution pattern, but was not substantially base-dependent.

PMID- 10206557
TI  - Investigation of the S3 site of thrombin: design, synthesis and biological
      activity of 4-substituted 3-amino-2-pyridones incorporating P1-argininals.
AB  - A novel scaffold for P4-P2 dipeptide mimics containing a rigid pyridone spacer
      was designed based on a virtual library strategy. Several selected nonpeptidic 4
      aralkyl or 4-alkylpyridones incorporating a P1-argininal sequence were prepared.
      The modeling studies, synthesis and biological activities of these unique
      pyridone derivatives are reported herein.

PMID- 10206558
TI  - Design, synthesis, and structure-activity relationship studies of himbacine
      derived muscarinic receptor antagonists.
AB  - A parallel synthesis of racemic himbacine analogs was carried out by N-alkylation
      of various commercially available cyclic amine derivatives with the alkylating
      agent 4 which bears the tricyclic unit of himbacine. Several of these analogs
      have potency comparable to that of himbacine, albeit lacking the desired
      selectivity. Structure-activity relationship studies support the existence of a
      hydrophobic pocket in the receptor where the piperidine ring of dihydrohimbacine
      binds.

PMID- 10206559
TI  - N,N-dialkyl-dipeptidylamines as novel N-type calcium channel blockers.
AB  - Selective N-type voltage sensitive calcium channel (VSCC) blockers have shown
      utility in several models of stroke and pain. We are especially interested in
      small molecule N-type calcium channel blockers for therapeutic use. Herein, we
      report a series of N,N-dialkyl-dipeptidylamines with potent functional activity
      at N-type VSCCs and in vivo efficacy. The synthesis, SAR, and pharmacological
      evaluation of this series are discussed.

PMID- 10206560
TI  - The pain medicine and primary care community rehabilitation model: monitored care
      for pain disorders in multiple settings.

PMID- 10206561
TI  - AAPM president's message. Presidential address. American Academy of Pain
      Medicine.

PMID- 10206562
TI  - Block of pinprick and cold sensation poorly correlate with relief of
      postoperative pain during epidural analgesia.
AB  - OBJECTIVE: To test the following hypotheses: there is a correlation between
      spread of epidural analgesia as assessed postoperatively by pinprick/cold test
      and postoperative pain intensity; block of pinprick/cold sensation is associated
      with absence of postoperative pain. DESIGN: Correlation analysis on prospectively
      collected data. SETTING: University hospital. PATIENTS: One hundred patients
      undergoing major surgery. Consecutive sample. INTERVENTIONS: Patients received an
      epidural infusion of bupivacaine 1 mg/ml, fentanyl 2 microg/ml, and epinephrine 2
      microg/ml for at least 48 hours postoperatively. The infusion rate was adjusted
      according to pain intensity, occurrence of hypotension, or motor block. OUTCOME
      MEASURES: Assessments were made on three time points: 20-24 hours, 32-36 hours,
      and 4248 hours after extubation. Assessments included pinprick and cold
      sensitivity from C2 to S5, pain intensity (visual analogue scale, VAS) at rest,
      after cough, and after mobilization. Data were analyzed by multiple regression.
      RESULTS: VAS significantly decreased with increasing spread (number of dermatomes
      for which hyposensitivity to pinprick or cold was observed). Spread could explain
      only 2-5% of the variability of VAS. Absence of both pinprick and cold sensation
      at all dermatomes corresponding to the surgical wound was frequently associated
      with pain. A high proportion of patients manifesting an upper level of block
      above T5 had pain after abdominal surgery. CONCLUSIONS: Spread and efficacy of
      epidural analgesia as assessed by pinprick and cold stimulation correlate poorly
      with postoperative pain. These methods are of limited value both as clinical
      indicators of the efficacy of postoperative pain control and for investigating
      the effect of epidural drugs and techniques.

PMID- 10206563
TI  - Pain measurement in persons with intellectual disabilities.
AB  - OBJECTIVE: The goal was to study the utility of nonverbal facial expressions as a
      research tool for assessing pain in persons with intellectual disabilities.
      Biases and stereotypes related to age, gender, physical attractiveness, and
      intellectual disability that may influence the ability of observers to evaluate
      pain reactions were also examined. DESIGN: Facial reactions to an intramuscular
      injection of 40 adults (mean age = 49.6 years) with an intellectual disability
      were videotaped and objectively examined using the Facial Action Coding System.
      Self-reported pain ratings were obtained using a Colored Visual Analogue Scale
      for pain. Pain reactions were also rated by untrained observers. RESULTS: A
      significant proportion of participants (35%) was unable to provide valid self
      report. The intensity of objectively coded facial activity as well as observer
      rated pain intensity showed significant increases from baseline to injection
      segments. Observers' pain ratings were primarily determined by the intensity of
      facial activity and were not significantly affected by stereotypes based on
      perceived level of intellectual disability, gender, age, or physical
      attractiveness. CONCLUSIONS: The findings support the validity of both
      objectively coded and observer-rated facial expressions of pain as research tools
      in treatment outcome studies involving persons with intellectual disabilities.
      Self-report has substantial limitations for the assessment of pain in this
      population.

PMID- 10206564
TI  - Empirical test of the factor structure of the West Haven-Yale Multidimensional
      Pain Inventory.
AB  - OBJECTIVE: Although the West Haven-Yale Multidimensional Pain Inventory (MPI) is
      frequently used in clinical evaluation and research with chronic pain patients,
      few studies have reported item-level factor analyses. After performing such an
      analysis, Bernstein et al. (Spine 1995;20:956-63) reported lack of independence
      between the solicitous and distracting response scales in section II as well as
      the activities away from home and social activities scales in section III. They
      suggested that the combination of these scales would improve the internal
      structure of the MPI. The purpose of this study was to perform a confirmatory
      factor analysis testing whether the MPI would be improved by the consolidation of
      these scales. In addition, a third, empirical model was generated for comparison
      with the West Haven-Yale and Bernstein models. DESIGN: This study used
      exploratory and confirmatory factor analysis on two independent samples of
      chronic pain patients (n = 472 and n = 346) to test hypotheses regarding the
      factor structure of the MPI. RESULTS AND CONCLUSION: Principal axis factor
      analysis resulted in an empirical model that suggested that the primary
      psychometric problem of the MPI was lack of item-factor discrimination for
      several items. When the three models were tested using confirmatory factor
      analysis, improvement in model fit occurred when cross loading items were
      excluded. Nevertheless, the goodness of fit of original factor structure was
      adequate, suggesting it would be premature to suggest changes in this instrument.

PMID- 10206565
TI  - Does gender affect appraisal of pain and pain coping strategies?
AB  - OBJECTIVE: To investigate the impact of gender and a set of pain characteristics
      on the threat or challenge appraisal of pain and the impact of these appraisals
      on the coping strategies used to manage the pain. DESIGN: This study used a
      community telephone survey to examine these relationships for a troublesome pain
      experienced by respondents in the 2 weeks preceding the interview. STUDY
      RESPONDENTS: The sampling frame consisted of 1,430 households randomly selected
      from the Halifax-Dartmouth-Bedford community. Of the 390 respondents with a
      troublesome pain in the 2 weeks preceding the interview, 309 respondents agreed
      to participate (79% response rate). RESULTS: Women tended to report more pain
      located in the head and more somatic problems. They reported significantly more
      intense pain. For women and men, the most important impact on threat appraisal of
      pain was overall interference of pain and emotional upset due to pain. These two
      variables accounted for 48% of the variance in threat appraisal for women and 37%
      of the variance for men. There was no gender difference in emotional upset due to
      pain or in the impact of emotional upset on threat appraisal. There was no gender
      difference in challenge appraisal. Threat appraisal was associated with increased
      catastrophizing whereas challenge appraisal was associated with positive self
      statements. Women reported significantly more problem solving, social support,
      positive self-statements, and palliative behaviors than did men. CONCLUSIONS:
      Interference of pain has a greater impact on threat appraisal of pain for women.
      Increasing threat appraisal is associated with health care utilization for women,
      but women's more frequent use of several coping strategies is unrelated to their
      appraisal of pain. Appraisal of pain may have important implications on coping
      and overall well-being of women and men.

PMID- 10206566
TI  - Validation of the coping with health, injuries, and problems scale in a chronic
      pain sample.
AB  - OBJECTIVE: The Coping with Health, Injuries, and Problems (CHIP) Scale is a self
      report instrument that is designed for diverse patient populations to provide
      measures of emotion-focused (e.g., emotional preoccupation) and task-oriented
      (e.g., palliative, instrumental, distraction) responses to injury. The present
      investigation assessed the factor structure, reliability, and validity of the
      measure in patients (n = 203) with chronic musculoskeletal pain. METHOD: Patients
      were administered questionnaires, including the CHIP Scale, and measures of pain
      coping strategies, adjustment, and personality. RESULTS: The factor structure,
      with one exception, was replicable, and the subscale reliabilities were
      acceptable. The subscales related in predictable ways to other similar
      questionnaires, to pain adjustment, and to personality. CONCLUSION: Overall, the
      CHIP Scale is both reliable and valid in assessing responses to chronic pain.
      Researchers and clinicians who want to use a psychometrically sound measure of
      response to illness that is applicable across diverse patient populations are
      encouraged to consider this measure.

PMID- 10206567
TI  - Chronic pain management in a health maintenance organization.
AB  - OBJECTIVE: The purpose of this study is to investigate the management of chronic
      pain in a large health maintenance organization using cognitive-behavioral
      techniques and a blinded control group. DESIGN: Subjects were randomized into two
      groups. All participants completed a self-administered baseline questionnaire and
      were mailed a self-administered 6-month follow-up questionnaire. SETTING: This
      study examines chronic pain management in a large, established health maintenance
      organization. PATIENTS: Patients were members of a health maintenance
      organization, had pain for at least 6 months, and had failed all known treatment
      regimens. INTERVENTIONS: The treatment group participated in a 16-hour, 8-week
      class teaching cognitive-behavioral techniques, the relaxation response,
      meditation, and stress management. The minimal treatment group received a home
      study manual. OUTCOME MEASURES: Behavioral outcomes, function, and pain severity
      and also patient satisfaction were measured. RESULTS: Both the treatment and
      minimal treatment groups exhibited improvement in pain severity, negative mood,
      pain affect, and pain interference with the patient's life. CONCLUSION: Gains
      were achieved in pain severity, negative mood, pain affect, self-control, and
      pain interference with the patient's life. Other behavioral variables and
      activity did not improve. Except in self-control, pain affect, and distracting
      responses from their significant others, the blinded minimal treatment group
      demonstrated similar findings. Patient satisfaction with treatment strongly
      favored the treatment group with over 78% of the treatment participants satisfied
      with the care provided.

PMID- 10206568
TI  - Cognitive-behavioral treatment in unselected rheumatoid arthritis outpatients.
AB  - OBJECTIVE: This trial was performed to evaluate the efficacy of an adjunctive
      cognitive-behavioral treatment compared with rheumatological treatment alone in
      unselected rheumatoid arthritis outpatients. DESIGN: A prospective randomized
      control design was used. Change in medication during treatment was controlled by
      matching therapy- and control-group subjects according to this change in
      medication, sex, age, duration of disease, and functional class. SETTING: A
      rheumatological outpatient clinic, University of Goettingen, Germany. PATIENTS:
      Fifty-five consecutive outpatients with a diagnosis of rheumatoid arthritis (age
      52.7 years, 74.5% female, duration of disease 9.4 years) finished the study.
      INTERVENTIONS: Subjects received routine care by the rheumatologists and routine
      medical treatment. Cognitive-behavioral treatment subjects (n = 19) received
      adjunctive standardized cognitive-behavioral group treatment with 12 weekly
      sessions. OUTCOME MEASURES: Outcome measures included disease activity variables,
      pain variables (pain intensity, affective pain), psychological symptoms, and
      coping. RESULTS: Subjects mostly demonstrated an increasing disease activity
      during treatment; change in medication during treatment was necessary in some
      patients. In the cognitive-behavioral treatment group the course of rheumatoid
      arthritis seemed less progressive than in the control group. The core effects of
      cognitive-behavioral treatment pertain more to improved coping, emotional
      stabilization, and reduced impairment than to reduced pain intensity. Passive,
      emotion-focused coping, helplessness, depression, anxiety, affective pain, and
      fluctuation of pain are reduced, "Acceptance of Illness" is improved.
      CONCLUSIONS: Cognitive-behavioral therapy has proven an effective adjunct to
      standard treatment of rheumatoid arthritis outpatients. These effects were shown
      in an unselected sample with increasing disease activity and with comparable
      changes in medication during treatment. We recommend cognitive-behavioral
      treatment as an desirable adjunct to standard medical treatment of rheumatoid
      arthritis.

PMID- 10206569
TI  - Subcutaneous infusion of lidocaine provides effective pain relief for CRPS
      patients.
AB  - CASE REPORT: Nine patients with Complex Regional Pain Syndrome types I and/or II
      (CRPS), previously known as reflex sympathetic dystrophy (RSD) and causalgia,
      respectively, were selected for treatment with a continuous four to eight week
      subcutaneous infusion of 10% lidocaine. RESULTS AND CONCLUSIONS: Five patients
      completed the infusion treatment. The treatment significantly alleviated much of
      the pain and other symptomatology (i.e., dysesthesia, allodynia, hyperpathia,
      color and temperature changes, decreased range of motion of involved extremities,
      changes in hair and nail growth, etc.) commonly observed for CRPS/RSD patients.
      Upon discontinuation of the continuous subcutaneous infusion, patients appear to
      maintain the pain relief obtained. Periodic maintenance infusions may be needed.

PMID- 10206570
TI  - Oral acyclovir after penetrating keratoplasty for herpes simplex keratitis.
AB  - OBJECTIVE: To determine the efficacy of systemic acyclovir in decreasing
      complications and improving the outcome of penetrating keratoplasty for herpes
      simplex virus (HSV) keratitis. METHODS: Retrospective study of 53 primary
      penetrating keratoplasties for HSV keratitis at an eye hospital from January 1,
      1989, through December 31, 1996. Medical records were analyzed for history of HSV
      keratitis, preoperative neovascularization, and disease activity. Postoperative
      use of acyclovir, recurrence of HSV keratitis, rejection, uveitis or edema, and
      graft failure were evaluated. RESULTS: Twenty-four patients (mean +/- SD follow
      up, 44.7 +/- 32.6 months) received no acyclovir and were compared with 20
      patients, (mean +/- SD follow-up, 28.8 +/- 16.7 months), who received 400 mg
      acyclovir twice a day for at least 1 year. No patient in the acyclovir group had
      a recurrence of dendritic keratitis in the first year compared with 5 (21%) of
      the patients who did not receive acyclovir (P = .03). No patient had graft
      failure in the acyclovir group compared with 4 (17%) in the group without
      acyclovir after 1 year of follow-up (P = .06). CONCLUSION: Postoperative systemic
      acyclovir therapy after penetrating keratoplasty for HSV keratitis is associated
      with a reduced rate of recurrent HSV dendritic keratitis and possible graft
      failure at 1 year of follow-up.

PMID- 10206571
TI  - Severity and stability of glaucoma: patient perception compared with objective
      measurement.
AB  - OBJECTIVE: To elucidate the relationship between the subjective assessment in
      patients with glaucoma of (1) the severity of their visual loss, and (2) any
      deterioration in their visual function and their objective visual fields as
      measured by computed perimetry. DESIGN: First, patients completed a questionnaire
      relating to perceived visual disability and underwent binocular visual field
      testing. Second, a separate group of patients answered a question about perceived
      visual deterioration: their monocular visual field tests were analyzed
      retrospectively by pointwise linear regression to establish stability or
      deterioration. SETTING: The Glaucoma Service of a specialist eye hospital, which
      is a tertiary referral center and serves the local community. SUBJECTS: One
      hundred twenty-three patients with glaucoma including 62 for the severity arm of
      the study and 61 for the progression arm. MAIN OUTCOME MEASURES: Questionnaire
      responses, Esterman binocular disability score, and objective visual field
      deterioration. RESULTS: Questions strongly associated with Esterman binocular
      disability scores related to bumping into things, problems with stairs, and
      finding things that have been dropped. There was a strong association between
      perceived visual deterioration and measured bilateral visual field deterioration
      (P<.01). CONCLUSIONS: There is a strong association between some types of
      perceived visual disability and the severity of binocular field loss. A patient
      who notices gradual visual deterioration is twice as likely to have bilateral
      visual field deterioration as not. The findings in this sample of patients with
      mild-to-moderate glaucoma challenge the belief that glaucoma is an insidious
      process in which the symptoms do not appear until the end stage of the disease.

PMID- 10206572
TI  - Combined trabeculotomy and trabeculectomy as an initial procedure in
      uncomplicated congenital glaucoma.
AB  - OBJECTIVE: To review the results of combined trabeculotomy and trabeculectomy as
      a primary procedure in congenital glaucoma. METHODS: A retrospective review of
      100 consecutive eyes in 60 children undergoing surgery from December 30, 1991, to
      April 17, 1996. Features at initial examination, ie, corneal size and clarity,
      presence or absence of anterior segment structural abnormalities, and intraocular
      pressure (IOP), were noted. Data pertaining to perioperative use of mitomycin and
      the occurrence of complications were collected. After surgery, all patients had
      IOP, corneal integrity, and any postoperative complication recorded under chloral
      hydrate sedation. RESULTS: Mean preoperative IOP was 31 mm Hg. Average horizontal
      corneal diameter was 12.60 mm. Ninety-five eyes had corneal opacification. Twenty
      nine eyes had additional anterior segment anomalies, with ectropion uveae (n =
      11), Peters anomaly (n = 9), and partial aniridia (n = 7) being the most common.
      Mitomycin (0.2 or 0.4 mg/mL) was used in 87 eyes. Eleven eyes sustained hyphemas
      during or just after surgery. Total average follow-up was 304 days. Eyes in which
      no coexistent anterior segment anomalies were present had a 78% (49 eyes)
      operative success (IOP, <21 mm Hg); however, in eyes with associated anterior
      segment anomalies, the success rate was much lower (45% [18 eyes]). The
      difference in success rates between both groups was statistically significant (P
      = .03, chi2 test). CONCLUSIONS: Primary combined trabeculotomy and trabeculectomy
      was a useful initial procedure in uncomplicated congenital glaucoma. This was
      particularly true where corneal opacification, as in nearly all our eyes,
      precluded goniotomy, however, where other stigmata of anterior segment dysgenesis
      coexisted, results were significantly poorer.

PMID- 10206573
TI  - Treatment choice and quality of life in patients with choroidal melanoma.
AB  - OBJECTIVE: To determine if quality of life differs between patients with
      choroidal melanoma treated with enucleation and those treated with radiation
      therapy. MATERIALS AND METHODS: Patients treated for choroidal melanoma at 5
      Midwest centers were asked to participate. There were 65 participants treated
      with enucleation and 82 treated with radiation therapy. Quality of life was
      assessed using the Medical Outcome Study Short Form 36 and the National Eye
      Institute Visual Function Questionnaire and by the Time-Tradeoff interview
      method. RESULTS: The average length of follow-up was 4.9 years for the group
      treated with radiation therapy and 6.3 years for the group treated with
      enucleation (P = .05). After adjusting for age, sex, years of follow-up, and the
      number of chronic conditions, there were few differences in any of the quality-of
      life measures by treatment status. Participants in the group treated with
      radiation therapy were more likely to have higher (better) scores on the Vitality
      and Mental Component subscales of the Medical Outcome Study Short Form 36 than
      participants treated with enucleation. There were no differences on the National
      Eye Institute Visual Function Questionnaire or the Time-Tradeoff measures of
      quality of life. CONCLUSION: Choice of treatment for choroidal melanoma does not
      seem to be associated with large differences in quality of life in long-term
      follow-up.

PMID- 10206575
TI  - Histopathological features of vitreous removed at macular hole surgery.
AB  - OBJECTIVE: To describe the histopathological features of the vitreous removed at
      surgery for macular holes in 200 consecutive cases. METHODS: The complete
      vitrectomy specimen in each case was concentrated by means of cellulose membrane
      filters and stained for light microscopy. The cases were organized into 5
      categories: (1) all cases (N = 200), (2) eyes without previous vitrectomy (n =
      174), (3) eyes with previous vitrectomy (n = 26), (4) idiopathic cases (n = 143),
      and (5) traumatic (accidental or surgical) cases (n = 31). The type and frequency
      of tissue fragments present in the vitreous were determined for each case.
      RESULTS: Fibrocellular and cellular membrane fragments were found in a minority
      of cases in all categories. Retinal fragments were a rare finding, present in
      only 4 cases. Inflammation was present in 57 (28.5%) of all cases. CONCLUSIONS:
      The absence of fibrocellular and cellular membrane fragments in the majority of
      cases suggests that mechanisms other than cellular proliferation are important in
      the pathogenesis of macular holes. These fragments are, however, the likely
      histopathological correlate of the opercula that are often observed clinically in
      patients with macular hole. Opercula rarely if ever contain retinal fragments,
      and thus are better termed pseudo-opercula, as has been previously suggested. The
      cellular proliferation and inflammation that are observed in some of the cases
      are likely a secondary or reactive process.

PMID- 10206574
TI  - Treatment of paraneoplastic visual loss with intravenous immunoglobulin: report
      of 3 cases.
AB  - BACKGROUND: Paraneoplastic visual loss is an autoimmune disorder believed to be
      caused by the remote effects of cancer on the retina (cancer-associated
      retinopathy [CAR]) or optic nerve. Both disorders may result in rapid and
      complete blindness. Spontaneous recovery of vision has not been reported. The
      serum of patients with CAR contains autoantibodies against recoverin, enolase, or
      unidentified retinal proteins. Autopsy examination results of eyes of blind
      patients with CAR show complete absence of the retinal neurons involved in
      phototransduction. Corticosteroids and plasmapheresis are the only treatment
      options previously described. OBJECTIVE: To treat paraneoplastic visual loss.
      DESIGN AND METHODS: Three patients with metastatic cancer developed rapidly
      progressive loss of vision. The first patient had visual acuity of hand movements
      in each eye before intravenous immunoglobulin treatment. The second patient had
      visual acuity of light perception in both eyes. The third patient's visual acuity
      was 20/400 OD and 20/20 OS. Diagnostic tests included magnetic resonance imaging
      of the head and cytologic examination of the cerebrospinal fluid to exclude
      metastasis as the cause of visual loss and then an electroretinogram and serum
      tests for autoantibodies against retinal antigens to confirm the clinical
      diagnosis of CAR. Patients 1 and 2 were treated with intravenous immunoglobulin
      (400 mg/kg per day) for 5 days; however, patient 3 received only a single dose
      due to adverse effects consisting of shortness of breath and itching. RESULTS:
      Within 24 hours of taking the first dose of intravenous immunoglobulin, the
      visual acuity of patient 1 improved from hand movements only in both eyes to
      20/50 OD and 20/200 OS. After the third day of treatment, visual acuity in the
      left eye further improved to 20/40. Even with the improved acuity, Goldmann
      visual field perimetry results showed poor responses in both eyes. However, 2
      weeks later there was marked visual field improvement, and visual acuity was
      maintained at 20/50 OD and 20/40 OS. Patient 2 had no improvements and continued
      to have light perception in both eyes. Patient 3 had improvements in visual field
      defects but remained 20/400 OD and 20/20 OS. CONCLUSION: Intravenous
      immunoglobulin may be another treatment option offered to patients with
      paraneoplastic visual loss in addition to corticosteroids or plasmapheresis
      because a review of the medical literature has shown no spontaneous improvements
      of visual function without treatment.

PMID- 10206576
TI  - Surgical treatment of paralysis of the inferior division of the oculomotor nerve.
AB  - BACKGROUND: Paralysis of the inferior division of the oculomotor nerve is
      relatively rare. Little has been written about its surgical treatment. METHODS:
      Five patients with paralysis of the inferior division of the oculomotor nerve
      were treated with transposition of the superior rectus muscle toward the
      insertion of the medial rectus muscle, transposition of the lateral rectus muscle
      toward the insertion of the inferior rectus muscle, and tenotomy of the superior
      oblique tendon in the affected eye. RESULTS: All 5 patients had a satisfactory
      outcome. They were free of diplopia in the primary position as of their last
      examination. Follow-up ranged from 3 to 10 years after surgery. CONCLUSION:
      Paralysis of the inferior division of the oculomotor nerve can be adequately
      treated by simultaneous transposition of the superior rectus muscle toward the
      insertion of the medial rectus muscle, transposition of the lateral rectus muscle
      toward the insertion of the inferior rectus muscle, and tenotomy of the superior
      oblique tendon in the affected eye.

PMID- 10206577
TI  - Human conjunctival mast cells: expression of Fc epsilonRI, c-kit, ICAM-1, and
      IgE.
AB  - OBJECTIVE: To characterize the expression and regulation of conjunctival mast
      cell surface receptors important in allergic inflammation. METHODS: Mast cells
      were isolated from human conjunctival tissues of cadavers. Mast cell surface
      markers were identified using flow cytometry with antibodies to IgE, Fc
      epsilonRI, c-kit, and intercellular adhesion molecule-1 (ICAM-1). We evaluated
      the effect of 24-hour tumor necrosis factor alpha (TNF-alpha) or interleukin 4
      (IL-4) incubation on the expression of mast cell c-kit, ICAM-1, and surface-bound
      IgE. RESULTS: Staining of mast cells (c-kit and/or tryptase positive) yielded
      positive results for all of the variables measured. The intensity of mast cell c
      kit staining increased with TNF-alpha incubation, but decreased below that of
      unstimulated mast cells when incubated with IL-4. Anti-ICAM-1 and anti-IgE
      staining were increased over that of unstimulated cells when incubated with TNF
      alpha or IL-4. CONCLUSIONS: In this model, TNF-alpha up-regulates mast cell
      surface receptors and cell-bound IgE. Interleukin 4 up-regulates mast cell ICAM-1
      and cell-bound IgE, but down-regulates c-kit. CLINICAL RELEVANCE: Conjunctival
      mast cells play a critical role in the pathogenesis of atopic ocular disease.
      Characterization of the expression and regulation of mast cell surface receptors
      is important to the development of potential novel treatments for ocular
      inflammation.

PMID- 10206578
TI  - Retinal neovascularization is suppressed with a matrix metalloproteinase
      inhibitor.
AB  - OBJECTIVES: To determine the role of extracellular proteinases in ischemia
      induced retinal neovascularization in an animal model and to examine the effect
      of proteinase inhibitors on retinal neovascularization. METHODS: Retinal
      neovascularization was induced in newborn mice exposed to 75% oxygen for 5 days,
      followed by room air. Retinal extracts underwent zymographic analysis to measure
      the activity of urokinase and matrix metalloproteinases (MMPs). Some animals
      under the same conditions also received intraperitoneal injections of an MMP
      inhibitor. Histological analysis was done to quantitate the neovascular response
      in these animals. RESULTS: Levels of urokinase and MMPs (MMP-2 and MMP-9) in
      retinas were significantly increased in animals with induced retinal
      neovascularization. Neovascularization was significantly inhibited with
      intraperitoneal administration of an MMP inhibitor. CONCLUSION: Systemic
      inhibition of MMPs may have therapeutic potential in preventing retinopathy
      associated with retinal neovascularization. CLINICAL RELEVANCE: Because up
      regulation and activation of proteinases represents a final common pathway in the
      process of retinal neovascularization, pharmacological intervention of this
      pathway may be an alternative therapeutic approach to proliferative retinopathy.

PMID- 10206579
TI  - Variation of clinical expression in patients with Stargardt dystrophy and
      sequence variations in the ABCR gene.
AB  - OBJECTIVE: To report the spectrum of ophthalmic findings in patients with
      Stargardt dystrophy or fundus flavimaculatus who have a specific sequence
      variation in the ABCR gene. PATIENTS: Twenty-nine patients with Stargardt
      dystrophy or fundus flavimaculatus from different pedigrees were identified with
      possible disease-causing sequence variations in the ABCR gene from a group of 66
      patients who were screened for sequence variations in this gene. METHODS:
      Patients underwent a routine ocular examination, including slitlamp biomicroscopy
      and a dilated fundus examination. Fluorescein angiography was performed on 22
      patients, and electroretinographic measurements were obtained on 24 of 29
      patients. Kinetic visual fields were measured with a Goldmann perimeter in 26
      patients. Single-strand conformation polymorphism analysis and DNA sequencing
      were used to identify variations in coding sequences of the ABCR gene. RESULTS:
      Three clinical phenotypes were observed among these 29 patients. In phenotype I,
      9 of 12 patients had a sequence change in exon 42 of the ABCR gene in which the
      amino acid glutamic acid was substituted for glycine (Gly1961Glu). In only 4 of
      these 9 patients was a second possible disease-causing mutation found on the
      other ABCR allele. In addition to an atrophic-appearing macular lesion, phenotype
      I was characterized by localized perifoveal yellowish white flecks, the absence
      of a dark choroid, and normal electroretinographic amplitudes. Phenotype II
      consisted of 10 patients who showed a dark choroid and more diffuse yellowish
      white flecks in the fundus. None exhibited the Gly1961Glu change. Phenotype III
      consisted of 7 patients who showed extensive atrophic-appearing changes of the
      retinal pigment epithelium. Electroretinographic cone and rod amplitudes were
      reduced. One patient showed the Gly1961Glu change. CONCLUSIONS: A wide variation
      in clinical phenotype can occur in patients with sequence changes in the ABCR
      gene. In individual patients, a certain phenotype seems to be associated with the
      presence of a Gly1961Glu change in exon 42 of the ABCR gene. CLINICAL RELEVANCE:
      The identification of correlations between specific mutations in the ABCR gene
      and clinical phenotypes will better facilitate the counseling of patients on
      their visual prognosis. This information will also likely be important for future
      therapeutic trials in patients with Stargardt dystrophy.

PMID- 10206580
TI  - Human T-cell lymphotropic virus type 1 infection and ocular manifestations in Sao
      Paulo, Brazil.
AB  - OBJECTIVES: Although human T-cell lymphotropic virus type 1 (HTLV-1)-associated
      uveitis has been well recognized in Japan, related studies in Brazil are scarce.
      We performed a serologic survey for HTLV-1 infection among patients with uveitis
      and investigated the ocular findings in HTLV-1-asymptomatic carriers. METHODS:
      One hundred ninety serum samples from patients with uveitis of determined (n =
      137) and undetermined origins (n = 53) being examined at the Uveitis Service,
      University of Sao Paulo, Sao Paulo, Brazil, underwent testing using HTLV enzyme
      linked immunosorbent assay and discriminatory Western blots. One hundred five
      asymptomatic blood donors and/or their relatives who were seropositive for HTLV-1
      (carrier group) and 105 age- and sex-paired blood donors who were seronegative
      for HTLV-1 (control group) underwent ocular evaluation. For the statistical
      analysis, chi2 test was used. RESULTS: Only 1 patient with uveitis was
      seropositive for HTLV- 1, and she belonged to the group with uveitis of
      undetermined origin. Results of tear films were evaluated in 52 carriers. The
      prevalence of a decreased tear break-up time was significantly higher in the
      carrier compared with the control group (P = .02). Two carriers had
      keratoconjunctivitis sicca. Three of the 105 carriers exhibited mild uveitis
      (cells in the vitreous, retinal and choroidal infiltrates, retinal vasculitis,
      and bilateral pars planitis). Retinal pigmentary changes were found in both
      groups (no statistical difference). CONCLUSIONS: Early tear abnormalities may be
      present in asymptomatic carriers, and mild uveitis may be found among them. The
      relatively low seroprevalence of HTLV-1 in the Brazilian population made it
      difficult to establish the real importance of HTLV-1-associated uveitis among our
      patients with uveitis.

PMID- 10206581
TI  - Sildenafil (Viagra) and ophthalmology.

PMID- 10206582
TI  - Posttraumatic endophthalmitis.

PMID- 10206583
TI  - What gives rise to impaired smooth pursuit in the relatives of patients with
      schizophrenia?

PMID- 10206584
TI  - Reviewers, authors, and editors: balance of power.

PMID- 10206585
TI  - Recurrent macular corneal dystrophy type II 49 years after penetrating
      keratoplasty.
AB  - Recurrence of macular corneal dystrophy after keratoplasty is rare. We report
      light microscopic, immunohistochemical, electron microscopic, and serologic
      findings in a 78-year-old woman who underwent regrafting 49 years following the
      first penetrating keratoplasty. Examination of the corneal button revealed
      deposits of glycosaminoglycans in the graft beneath the Bowman layer, throughout
      the stroma, and in the endothelium with positive staining for antigenic keratan
      sulfate. By transmission electron microscopy, intracellular and extracellular
      deposits of a fibrillogranular material were detected in the stroma, Descemet
      membrane, and endothelium. The serum level of antigenic keratan sulfate was
      normal. Our findings indicate that macular corneal dystrophy type II may show
      late recurrence after penetrating keratoplasty with intense deposition of
      antigenic keratan sulfate in all corneal layers.

PMID- 10206586
TI  - Pars plana vitrectomy and subretinal surgery for ocular toxocariasis.
AB  - The clinical course of ocular toxocariasis and the chronological development of
      peripheral retinal and macular granulomas are reported. Removing the epiretinal
      as well as subretinal component of the granuloma via pars plana vitrectomy and
      retinotomy techniques yielded an excellent clinical result. Clinicopathologic
      correlation of the specimen confirmed the diagnosis with histological evidence of
      degenerated larval structures in granulomatous inflammation.

PMID- 10206587
TI  - Primary orbital Ewing sarcoma in a middle-aged woman.
AB  - A 43-year-old woman had unilateral exophthalmos caused by primary orbital Ewing
      sarcoma. Specialized immunohistochemical stains, primarily MIC-2 (CD99), aided in
      the diagnosis of Ewing sarcoma. Twenty-two months after radiotherapy and
      multiagent chemotherapy, the patient remained tumor free. To our knowledge, this
      is the first reported case of orbital Ewing sarcoma to present in an adult beyond
      the fourth decade of life.

PMID- 10206588
TI  - Corneal toxicity associated with latanoprost.

PMID- 10206589
TI  - Removal of a fishhook in the eyelid and cornea using a vertical eyelid-splitting
      technique.

PMID- 10206590
TI  - Traumatic total iridectomy due to iris extrusion through a self-sealing cataract
      incision.

PMID- 10206591
TI  - Treatment of conjunctival corneal intraepithelial neoplasia with topical
      mitomycin C.

PMID- 10206592
TI  - Giant retinal pigment epithelial tear after trabeculectomy.

PMID- 10206594
TI  - Photographs of intralenticular hemorrhage following blunt ocular trauma.

PMID- 10206593
TI  - Nailing down the diagnosis: imaging intraocular foreign bodies.

PMID- 10206595
TI  - The John Stanley Coulter Lecture. Predicting recovery after spinal cord injury: a
      rehabilitation imperative.

PMID- 10206596
TI  - Swallowing disorders in severe brain injury: risk factors affecting return to
      oral intake.
AB  - OBJECTIVE: To determine the incidence and type of swallowing disorders that
      accompany severe brain injury and to identify factors that affect oral intake.
      DESIGN: Inception cohort study. SETTING: Level I trauma center. PATIENTS:
      Consecutively admitted patients with severe brain injury who achieved cognitive
      levels during admission to assess swallowing and who did not sustain injuries
      preventing swallowing assessment (n = 54). MAIN OUTCOME MEASURES: Type of
      swallowing abnormalities and presence of aspiration evident on videofluoroscopic
      swallow studies (VFSS), days to initiation and achievement of oral feeding,
      ventilation days, presence of a tracheostomy, and cognitive levels at initiation
      and achievement of oral feeding. RESULTS: Sixty-one percent of subjects exhibited
      abnormal swallowing. Loss of bolus control and reduced lingual control occurred
      most commonly. Aspiration rate was 41%. Normal swallowers achieved oral feeding
      in 19 days versus 57 days for abnormal swallowers. Rancho Los Amigos (RLA) Level
      IV was needed for initiation of oral feeding; Level VI was needed for total oral
      feeding. Risk factors for abnormal swallowing included: lower admission Glasgow
      Coma Scale (GCS) and RLA scores, presence of a tracheostomy, and ventilation time
      longer than 2 weeks. Risk factors for aspiration were lower admission GCS and RLA
      scores. CONCLUSIONS: Swallowing disorders and behavioral/cognitive skills are
      frequently present in patients with severe brain injury and significantly affect
      oral intake of food. Persons who swallow abnormally take significantly longer to
      start eating and to achieve total oral feeding, and they require nonoral
      supplementation three to four times longer than those who swallow normally.

PMID- 10206597
TI  - Rapid growth of rehabilitation services in traditional community-based nursing
      homes.
AB  - OBJECTIVE: To describe the changes in rehabilitation therapy services in nursing
      homes based in the community during a period of rapid escalation of Medicare
      payments to nursing homes. SETTING: All Medicaid-certified nursing homes in Ohio.
      SUBJECTS: The 52,705 residents newly admitted to nursing homes in 1994 and 1995.
      DESIGN: Retrospective trend analysis of administrative data. MAIN OUTCOME
      MEASURES: For newly admitted residents receiving 90 or more minutes of
      rehabilitation therapy per week, the trends in percentage and in the amount and
      type of therapy received were determined for eight quarters. RESULTS: Of all
      newly admitted residents, 50.5% received 90 or more minutes of therapy. When they
      received such therapy it averaged 412 minutes per week (SD = 259). Those
      residents who received rehabilitation services increased by 2.2% each quarter
      (p<.001), and the amount of therapy they received increased by 6.4 minutes each
      quarter (p<.0001). All three types of rehabilitation therapy-physical,
      occupational, and speech-increased (p<.015) over the study period. CONCLUSIONS:
      The traditional nursing home is an important site for the provision of
      rehabilitation therapy services. Rehabilitation specialists should be aware of
      these trends as they plan for the future of rehabilitation. The effectiveness of
      this increased provision of therapy service in terms of measurable outcomes needs
      to be evaluated.

PMID- 10206598
TI  - Functional disability and rehabilitation outcome in right hemisphere damaged
      patients with and without unilateral spatial neglect.
AB  - OBJECTIVE: To evaluate the impact of unilateral spatial neglect (USN) on the
      rehabilitation outcome and long-term functioning in activities of daily living
      (ADL) and instrumental ADL (IADL) of right hemisphere damaged (RHD) stroke
      patients. DESIGN: Assessments of sensory-motor and cognitive impairment and of
      functional disability were conducted upon admission to rehabilitation, upon
      discharge from the rehabilitation hospital, and 6 months after discharge, up to a
      year postonset. SETTING: The Loewenstein Rehabilitation Hospital, which receives
      patients from all general hospitals in Israel. PATIENTS: Forty consecutive
      admissions of adult right-handed patients with a first, single, right hemispheric
      stroke proven by computed tomography. Based on their total score in the
      Behavioral Inattention Test for neglect, patients were divided into two groups:
      19 with neglect (USN+) and 21 without neglect (USN-). OUTCOME MEASURES:
      Functional Independence Measure, for ADL; The Rabideau Kitchen Evaluation, for
      IADL. RESULTS: Impairment and disability levels of RHD patients with and without
      USN were clearly differentiated. Neglect is associated with lower performance on
      measures of impairment (sensory-motor and cognitive), as well as on measures of
      disability in ADL and IADL. Differences were significant in all testing periods.
      The recovery pattern of USN+ patients is slower and more attenuated. In both
      groups, most improvement occurs in the first 5 months after onset. USN is the
      major predictor of rehabilitation outcome from admission to follow-up.
      CONCLUSIONS: The significance of neglect as a major source of stroke-related long
      term disability justifies further research efforts to develop appropriate
      therapeutic modalities for this complex, multifactorial syndrome.

PMID- 10206599
TI  - Relation of disability costs to function: spinal cord injury.
AB  - OBJECTIVE: This study evaluated the validity of the Functional Independence
      Measure (FIM instrument) in predicting (1) the number of minutes of daily
      assistance provided, (2) the cost of durable goods currently used, and (3) the
      number of paid helper hours provided daily to persons with spinal cord injury
      living in the community. DESIGN: A cross-sectional study. SUBJECTS: One hundred
      nine persons with spinal cord injury who were a median 6 years postdischarge from
      initial medical rehabilitation. RESULTS: A significant inverse linear
      relationship was observed between FIM scores and the square root values of the
      three cost-related measures. The FIM-18 and the FIM motor scores were the best
      single predictors of the square root of minutes of assistance (paid and/or
      unpaid) per day, explaining 85% of variance. The FIM motor measure was the best
      single predictor of square root of cost of durable goods, explaining 29% of
      variance. The Self-Care, FIM motor, and FIM-18 scores equally predicted square
      root of hours of paid help per day, explaining 58% of variance. CONCLUSION: The
      findings indicate FIM-related scores predict the amount of assistance needed and
      certain costs for persons with spinal cord injury disability.

PMID- 10206600
TI  - Mild traumatic brain injury from motor vehicle accidents: factors associated with
      return to work.
AB  - OBJECTIVES: To describe return to work (RTW) for motor vehicle accident (MVA)
      survivors with mild traumatic brain injury (MTBI) and to examine relationships
      between RTW and injury severity, cognitive impairment, social interaction,
      discharge disposition, and sociodemographics. DESIGN: Inception cohort assessed
      within 1 month of injury and at follow-up 6 to 9 months (mean = 7.4) after
      injury, for comparisons on outcome of RTW. SETTING: Tertiary care center in
      Toronto (time 1); at home for follow-up. PARTICIPANTS: Fifty patients with MTBI
      resulting from MVA who were consecutively admitted during a 20-month period
      ending April 1994. Thirteen of 63 eligible patients refused consent or were lost
      to follow-up. Mean age was 31; 62% were men. ELIGIBILITY CRITERIA: (1) patients
      had been working; (2) they had no history of head injury, neurologic disease, or
      psychiatric illness requiring hospitalization; and (3) they had no catastrophic
      impairment from accident. MAIN OUTCOME MEASURE: Return to work (at premorbid or
      modified level). RESULTS: Of the 42% who returned to work, 12% resumed their
      premorbid level of employment and 30% returned to modified work. There were
      significant differences (p<.05) between the groups in level of social
      interaction, premorbid occupation, and discharge disposition. On one test of
      cognitive functioning the difference was at p = .06. CONCLUSION: Social
      interaction, jobs with greater decision-making latitude, and discharge home were
      positively related to RTW for this population. Cognitive impairment within the
      first month was not a reliable indicator of RTW potential.

PMID- 10206601
TI  - Residential and home-based postacute rehabilitation of individuals with traumatic
      brain injury: a case control study.
AB  - OBJECTIVES: To compare the outcomes of severely brain-injured individuals treated
      in a postacute residential rehabilitation program with a matched sample of
      individuals receiving limited services in their homes or on an outpatient basis.
      DESIGN: Controlled study using a matched design in a before-and-after trial and a
      1-year follow-up trial. SETTING: A postacute community-based residential
      rehabilitation program or in the homes of patients. PATIENTS AND OTHER
      PARTICIPANTS: The treatment group included all persons admitted consecutively for
      rehabilitation to the postacute residential program over a 3-year period (n =
      23). All subjects had severe traumatic brain injury. The comparison group was
      selected from the roster of a support group on the basis of a systematic matching
      procedure. Matching variables included gender, age, length of coma, time since
      injury, and level of disability. Subjects of the two groups were matched on an
      individual basis. MAIN OUTCOME MEASURES: A functional assessment instrument
      (modified Health andActivity Limitations Survey [HALS]) and the Community
      Integration Questionnaire (CIQ). RESULTS: Individuals with traumatic brain injury
      who received residential-based postacute rehabilitation displayed a statistically
      significant increase in functional abilities when compared with a traditional
      (home-based) service group. More specifically, treatment subjects showed
      significantly greater improvement in motor skills and cognitive abilities.
      Treatment subjects also showed greater improvement in community integration,
      although this may have been accounted for by initial group differences.
      CONCLUSIONS: Postacute rehabilitation appears to be effective in improving
      function for individuals with severe brain injury. Residential-based services
      appear to produce greater functional improvement, whereas home-based services are
      more effective at maintaining community integration.

PMID- 10206602
TI  - Repeated passive stretching: acute effect on the passive muscle moment and
      extensibility of short hamstrings.
AB  - OBJECTIVE: To examine the response of short hamstring muscles to repeated passive
      stretching. DESIGN: A repeated measures design. SETTING: A university laboratory
      for human movement analysis in a department of rehabilitation. SUBJECTS: Students
      (7 men, 10 women) from the Department of Human Movement Sciences. MAIN OUTCOME
      MEASURES: The lift force, range of motion, pelvic-femoral angle, first sensation
      of pain, and electromyogram of the hamstrings were measured. RESULTS: Comparison
      of the data of the test group (n = 17) after five successive passive stretch
      tests by means of an instrumental straight-leg raising test showed no significant
      change of the variables passive muscle stiffness and extensibility (p>.05).
      CONCLUSION: The acute effect of repeated passive stretching of short hamstring
      muscles is negligible. With an instrumental straight-leg raising test, the
      relevant muscle variables can be examined noninvasively.

PMID- 10206603
TI  - Prediction of gait velocity in ambulatory stroke patients during rehabilitation.
AB  - OBJECTIVE: To quantify prediction of gait velocity in ambulatory stroke patients
      during rehabilitation. DESIGN: Single group (n = 42) at the beginning of
      rehabilitation (Test 1) and 8 weeks later (Test 2). SETTING: Inpatient
      rehabilitation. PATIENTS: Unilateral first stroke; informed consent; able to walk
      10 meters. MEASURES:  INDEPENDENT VARIABLES: Gait velocity at Test 1, age, time
      from stroke to Test 1, side of lesion, neglect. DEPENDENT VARIABLES: Gait
      velocity at Test 2, gait velocity change. RESULTS: The correlation between
      initial gait velocity and gait velocity outcome at Test 2 was of moderate
      strength (r2 = .62, p<.05). However, even at its lowest, the standard error of
      prediction for an individual patient was 9.4 m/min, with 95% confidence intervals
      extending over a range of 36.8 m/min. Age was a weak predictor of gait velocity
      at Test 2 (r2 = -.10, p<.05). Gait velocity change was poorly predicted. The only
      significant correlations were initial gait velocity (r2 = .10, p<.05) and age (r2
      = .10, p<.05). CONCLUSION: While the prediction of gait velocity at Test 2 was of
      moderate strength on a group basis, the error surrounding predicted values of
      gait velocity for a single patient was relatively high, indicating that this
      simple approach was imprecise on an individual basis. The prediction of gait
      velocity change was poor. A wide range of change scores was possible for
      patients, irrespective of their gait velocity score on admission to
      rehabilitation.

PMID- 10206604
TI  - Treadmill walking with partial body weight support versus floor walking in
      hemiparetic subjects.
AB  - OBJECTIVE: To compare the gait of hemiparetic subjects walking on a treadmill
      with various body weight supports and walking on the floor. DESIGN: Hemiparetic
      subjects walked on a treadmill, secured in a harness, with no body weight support
      and with 15% and 30% body weight relief, and walked on a floor. SETTING:
      Kinematic laboratory of a department of rehabilitation. SUBJECTS: Eighteen
      hemiparetic stroke patients. MAIN OUTCOME MEASURES: Gait cycle parameters and
      kinesiologic electromyogram of six muscles of the affected side and of two
      muscles of the nonaffected side. RESULTS: On the treadmill, patients walked more
      slowly because of a reduced cadence, with a longer single stance period of the
      paretic limb, more symmetrically, and with a larger hip extension (multivariate
      profile analysis, p<.05). The mean functional activities of the gastrocnemius
      muscle and of the first crest of the erector spinae of the paretic side were
      smaller on the treadmill (univariate test, p<.05). Further, the premature
      activity of the gastrocnemius muscle, indicating spasticity, was less on the
      treadmill (univariate test, p<.05); correspondingly the qualitative muscle
      pattern analysis revealed less co-contraction between the gastrocnemius and
      tibialis anterior muscles in 11 of the 18 subjects. CONCLUSIONS: Treadmill
      training with partial body weight support in hemiparetic subjects allows them to
      practice a favorable gait characterized by a greater stimulus for balance
      training because of the prolonged single stance period of the affected limb, a
      higher symmetry, less plantar flexor spasticity, and a more regular activation
      pattern of the shank muscles as compared with floor walking.

PMID- 10206605
TI  - Pelvic restraint effect on lumbar gluteal and hamstring muscle electromyographic
      activation.
AB  - OBJECTIVE: To evaluate the influence of pelvic restraint on electromyographic
      activation (neural drive) of the lumbar extensor, gluteal, and hamstring muscles
      during submaximal dynamic lumbar extension in an upright seated position. DESIGN:
      Randomized, balanced, crossover trial comparing the electromyographic activation
      of the lumbar, gluteal, and hamstring muscles during dynamic lumbar extension
      exercise with and without pelvic restraint. SETTING: Research laboratory at a
      private research university. SUBJECTS: Twelve apparently healthy men (ages 18 to
      50 yrs). INTERVENTION: Dynamic lumbar extension exercises. MAIN OUTCOME MEASURE:
      Electromyographic recordings. RESULTS: Pelvic restraint did not influence the
      relative activation of the lumbar, gluteal, or hamstring muscle groups (p< or
      =.05) during submaximal dynamic lumbar extension exercise. The relative
      activation of the gluteal muscles was significantly lower than that of the lumbar
      extensor and hamstring muscle groups. CONCLUSIONS: Pelvic restraint is not a
      requirement to promote neural drive to the lumbar musculature during submaximal
      dynamic lumbar extension exercise performed in an upright seated position.
      Submaximal lumbar extension exercise reduces the relative contribution of the
      gluteal muscles compared with a maximal voluntary isometric contraction.

PMID- 10206606
TI  - Cognitive status at admission: does it affect the rehabilitation outcome of
      elderly patients with hip fracture?
AB  - OBJECTIVES: To determine the effect of cognitive status at admission on
      functional gain during rehabilitation of elderly hip-fractured patients. DESIGN:
      Cohort study. SETTING: A hospital geriatric rehabilitation department. PATIENTS:
      Two hundred twenty-four elderly patients admitted consecutively for
      rehabilitation after surgery for hip fracture. MEASUREMENTS: Cognitive status was
      assessed by the Mini-Mental State Examination and the cognitive subscale of the
      Functional Independence Measure (cognFIM); functional status was assessed by the
      motor subscale of FIM; absolute functional gain was determined by the motor FIM
      gain (deltamotFIM); and relative functional gain (based on the potential for
      improvement) by the Montebello rehabilitation factor score (MRFS). RESULTS: A
      significant increase in FIM scores (19.7) occurred during rehabilitation, mainly
      due to motor functioning (19.1). When the relative functional gain (as measured
      by both motor MRFS efficacy [r = .591] and efficiency [r = .376] was compared
      with the absolute gain (as measured by deltamotFIM [r = .304]), a stronger
      association between cognFIM and the relative measures was found. In addition,
      motor FIM efficacy and efficiency were significantly lower in the cognitively
      impaired patients (p<.01). A better rehabilitation outcome was seen in patients
      with higher admission cognitive status, adjusting for the effects of age, sex,
      length of stay, and type of fracture (odds ratio = 2.2, 95% confidence interval
      1.5-3.7). CONCLUSIONS: Impaired cognitive status at admission lowered the
      rehabilitation outcome of elderly hip fracture patients. Cognitive impairment was
      strongly and directly associated with functional gain in these patients. Absolute
      motor gain appeared to be independent of cognitive status, whereas the relative
      motor gain depended on it. These findings support the implementation of
      comprehensive rehabilitation for selected cognitively impaired elderly hip
      fracture patients.

PMID- 10206607
TI  - Lower urinary tract dysfunction and disability status in patients with multiple
      sclerosis.
AB  - OBJECTIVE: To investigate the correlation between neurologic and urologic status
      in patients with multiple sclerosis (MS). MATERIALS AND METHODS: Between January
      1993 and December 1995, 116 patients with MS symptoms were fully assessed
      neurologically and urologically with urodynamic studies. RESULTS: Urodynamic
      abnormalities were detected in 104 patients (89.6%). Several significant
      relationships between urinary tract findings and neurologic dysfunction were: (1)
      the relation between voiding disorder as the presenting symptom of the disease
      and a higher severity of bladder dysfunction; (2) the relation between reduced
      bladder sensation and longer duration of voiding disorders, lower detrusor
      uninhibited contractions threshold, and lower bladder capacity; and (3) the
      relation between voiding disorders and cerebellar system score. Finally, a
      significant inverse relationship was found between detrusor hypocontractility and
      neurologic status (from the Expanded Disability Status Scale, pyramidal system
      score, and Barthel Index). CONCLUSIONS: In this series a high incidence of
      patients reported voiding disorder as the presenting symptom of MS. These
      patients also showed a higher severity of urodynamic disorders. They should be
      rigorously followed up. Furthermore, our data suggest that although the most
      common cause of altered bladder control in MS is spinal cord pathology,
      involvement of cortical centers and/or peripheral neuronal lesions may occur.

PMID- 10206608
TI  - Achievement of simple mobility milestones after stroke.
AB  - OBJECTIVES: To observe the mobility outcomes of an inpatient population of stroke
      patients grouped according to the Oxfordshire Community Stroke Project
      classification. STUDY DESIGN: "Mobility milestones," standardized measures of
      functional movement, were used to examine mobility recovery. PARTICIPANTS: Two
      hundred thirty-eight stroke patients admitted to the Western General Hospital,
      Edinburgh. MAIN OUTCOME MEASURES: Times taken to achieve four mobility
      milestones: 1-minute sitting balance, 10-second standing balance, a 10-step walk,
      and a 10-meter walk. RESULTS: For all subjects the median times to achieve the
      milestones were as follows: 1-minute sitting balance, day of stroke; 10-second
      standing balance, 3 days; 10-step walk, 6 days; and a 10-meter walk, 9 days.
      Subjects sustaining a partial anterior circulation infarct, lacunar infarct, or
      posterior circulation infarct achieved the mobility milestones most rapidly and
      generally had a shorter hospital stay. CONCLUSIONS: A hierarchical pattern of
      recovery of mobility reflecting variation between subgroups was observed.
      Predicted timescales for recovery of mobility are suggested.

PMID- 10206609
TI  - The Berg balance scale as a predictor of length of stay and discharge destination
      in an acute stroke rehabilitation setting.
AB  - OBJECTIVE: To examine the utility of the Berg Balance Scale (BBS) in predicting
      length of stay and discharge destination for patients admitted to a stroke
      rehabilitation unit. DESIGN: Retrospective study. SETTING: Regional tertiary
      inpatient stroke rehabilitation unit. PATIENTS: One hundred twenty-eight of 141
      patients admitted consecutively between January 1, 1995, and March 31, 1996. MAIN
      OUTCOME MEASURES: Length of stay and discharge destination. RESULTS: Admission
      BBS scores and Functional Independence Measure scores correlated with length of
      stay (r = -0.6 and -0.5, respectively, controlling for age). Logistic regression
      revealed that the following were independent predictors of being discharged home
      rather than to an institution (adjusted odds ratio, 95% confidence interval):
      admission BBS (1.09, 1.04-1.13), age (.89, .83-.95), and presence of family
      support (11.7, 3.1-44.3). CONCLUSIONS: Measuring the BBS scores of patients upon
      admission to an acute stroke rehabilitation unit may assist in approximating
      length of stay and predicting eventual discharge destination.

PMID- 10206610
TI  - Shoulder pain in wheelchair users with tetraplegia and paraplegia.
AB  - OBJECTIVE: To compare the prevalence and intensity of shoulder pain experienced
      during daily functional activities in individuals with tetraplegia and
      individuals with paraplegia who use manual wheelchairs. DESIGN: Self-report
      survey. SETTING: General community. PARTICIPANTS: Fifty-five women and 140 men,
      92 subjects with tetraplegia and 103 subjects with paraplegia who met inclusion
      criteria of 3 hours per week of manual wheelchair use and at least 1 year since
      onset of spinal cord injury. MAIN OUTCOME MEASURES: Respondents completed a
      demographic and medical history questionnaire and the Wheelchair User's Shoulder
      Pain Index (WUSPI), a measure of pain during typical daily activities. RESULTS:
      More than two thirds of the sample reported shoulder pain since beginning
      wheelchair use, with 59% of the subjects with tetraplegia and 42% of the subjects
      with paraplegia reporting current pain. Performance-corrected WUSPI scores were
      significantly higher in subjects with tetraplegia than in subjects with
      paraplegia. CONCLUSIONS: Both the prevalence and intensity of shoulder pain was
      significantly higher in subjects with tetraplegia than in subjects with
      paraplegia. Efforts to monitor and prevent shoulder pain should continue after
      rehabilitation.

PMID- 10206611
TI  - The reliability of postural x-rays in measuring pelvic obliquity.
AB  - OBJECTIVE: To assess the interrater and intrarater reliability of two methods of
      measurement of postural radiographs for determining the amount of pelvic
      obliquity. DESIGN: Four blinded raters evaluated the amount of pelvic obliquity
      using two measurement methods. SETTING: Physical medicine and rehabilitation
      outpatient clinic in a VA hospital. PARTICIPANTS: Fifty-two randomly chosen
      radiographs from 36 patients referred to a clinic to evaluate and treat pelvic
      obliquity. MEASURES: Amount of pelvic obliquity was determined by line of
      eburnation and by the intersulcate line. Pearson's correlation coefficients and
      percent agreements were calculated for each set of measurements. RESULTS:
      Pearson's correlation coefficients and percent agreements were higher for both
      interrater and intrarater measurements for the intersulcate line. CONCLUSION:
      Intersulcate line is the more reliable method for determining the amount of
      pelvic obliquity and will be used in future studies to assess the effectiveness
      of correcting pelvic obliquity to improve chronic back pain.

PMID- 10206612
TI  - Evaluation of selected ultralight manual wheelchairs using ANSI/RESNA standards.
AB  - OBJECTIVES: To provide data for clinicians and wheelchair users to compare the
      durability, strength, stability, and cost effectiveness of four different
      ultralight wheelchair models, and to compare the results of this study with those
      published for lightweight wheelchairs. DESIGN: Standards testing and cost
      effectiveness analysis of four wheelchair models from different manufacturers (12
      wheelchairs total). RESULTS: There were significant differences (p< or =.05) in
      the fatigue life and value (equivalent cycles per dollar) among the ultralight
      wheelchairs tested. There was also a significant difference (p< or =.05) in
      rearward stability tilt angle for the least and most stable configurations. There
      were no differences in forward and lateral stability. The ultralight wheelchairs
      (1,009,108 cycles) had significantly (p< or =.05) higher fatigue lives than
      previously reported for lightweight wheelchairs (187,370 cycles). The lightweight
      wheelchairs had a mean value of 210 cycles per dollar compared to 673 cycles per
      dollar for the ultralight wheelchairs. The difference in value for the
      lightweight and ultralight wheelchairs was statistically significant (p< or
      =.05). CONCLUSION: There were differences in the fatigue life and value among the
      four models of ultralight manual wheelchairs tested. This indicates that
      ultralight manual wheelchairs are not all of equal quality. The fatigue life and
      value of the ultralight manual wheelchairs were significantly higher than those
      previously reported for lightweight manual wheelchairs. This indicates that
      ultralight wheelchairs may be of higher quality than lightweight manual
      wheelchairs. Clinicians and consumers should seriously consider selecting an
      ultralight manual wheelchair to meet their wheelchair mobility needs.

PMID- 10206613
TI  - Hypothyroidism: its incidence and prevalence in adults older than 55 years of age
      in an acute rehabilitation unit.
AB  - OBJECTIVE: To investigate the incidence and prevalence of hypothyroidism in the
      acute rehabilitation unit. DESIGN: Retrospective chart review. SETTING: Inpatient
      rehabilitation unit. PATIENTS: Thirty-five men and 91 women older than the age of
      55 years (average, 74 years) separated into postsurgical (PS) and nonsurgical
      (NS) groups. Twenty-two men and 76 women were PS, 21 of whom had a history of
      hypothyroidism. Thirteen men and 15 women were NS, and 4 in this group had a
      history of hypothyroidism. MAIN OUTCOME MEASURES: Levels of thyroid-stimulating
      hormone and free thyroxine. RESULTS: There were 34 cases of hypothyroidism, a
      prevalence rate of 27%. The incidence of newly diagnosed cases was 9% (9 of 101).
      Six of the newly diagnosed cases were PS patients and three were NS patients.
      Eleven cases of undertreated hypothyroidism were found, in 9 PS patients and 2 NS
      patients. The rate of undertreated hypothyroidism in the PS population was 43% (9
      of 21); in the nonsurgical population, it was 50% (2 of 4). The overall rate of
      undertreated hypothyroidism for both PS and NS groups was 44% (11 of 25).
      CONCLUSION: There is a high prevalence of hypothyroidism on an inpatient
      rehabilitation unit and a high rate of undertreated hypothyroidism in PS
      patients. Screening high-risk patients is recommended.

PMID- 10206614
TI  - "White coat effect" induced by therapist's presence during speech therapy for
      stroke rehabilitation: a single case study.
AB  - The excessive pressor response triggered in patients by an alerting reaction to a
      doctor's presence has been termed the "white coat effect." A 68-year-old man with
      verbal apraxia after multiple lacunar infarctions was referred to the hospital
      for speech rehabilitation. He experienced difficulty in talking with the speech
      therapist during therapy sessions but not when talking with his friends or
      family. Because the therapist's presence was stressful to the patient, it was
      considered that his anxiety might produce an excessive increase in blood
      pressure. Blood pressure monitoring was performed during 2 separate days of
      speech therapies consisting of two sessions each. In one session, therapy was
      directed by the therapist; in the other, therapy was self-directed. The therapist
      directed approach substantially increased both systolic and diastolic blood
      pressures, whereas the self-directed therapy slightly increased only systolic
      pressure. It was concluded that the excessive pressor response seen in this
      patient during therapist-directed speech therapy resulted from the white coat
      effect induced by the therapist's presence.

PMID- 10206615
TI  - Pre-AIDS physical disability.

PMID- 10206616
TI  - Predicting neurologic recovery in SCI.

PMID- 10206617
TI  - Power and sample size calculations in case-control studies of gene-environment
      interactions: comments on different approaches.
AB  - Power and sample size considerations are critical for the design of epidemiologic
      studies of gene-environment interactions. Hwang et al. (Am J Epidemiol
      1994;140:1029-37) and Foppa and Spiegelman (Am J Epidemiol 1997;146:596-604) have
      presented power and sample size calculations for case-control studies of gene
      environment interactions. Comparisons of calculations using these approaches and
      an approach for general multivariate regression models for the odds ratio
      previously published by Lubin and Gail (Am J Epidemiol 1990; 131:552-66) have
      revealed substantial differences under some scenarios. These differences are the
      result of a highly restrictive characterization of the null hypothesis in Hwang
      et al. and Foppa and Spiegelman, which results in an underestimation of sample
      size and overestimation of power for the test of a gene-environment interaction.
      A computer program to perform sample size and power calculations to detect
      additive or multiplicative models of gene-environment interactions using the
      Lubin and Gail approach will be available free of charge in the near future from
      the National Cancer Institute.

PMID- 10206619
TI  - Biased tests of association: comparisons of allele frequencies when departing
      from Hardy-Weinberg proportions.
AB  - Association studies of genetic markers or candidate genes with disease are often
      conducted using the traditional case-control design. Cases and controls are
      sampled from genetically unrelated subjects, and allele frequencies compared
      between cases and controls using Pearson's chi-square statistic. An assumption of
      this analysis method is that the two alleles within each subject are
      statistically independent, at least when no association exists. This is
      equivalent to assuming that the frequencies of the genotypes in the general
      population comply with Hardy-Weinberg Equilibrium proportions, which may not
      always be the case. However, deviations from Hardy-Weinberg Equilibrium can
      inflate the chance of a false-positive association. These results demonstrate
      that when comparing the frequencies of two alleles between cases and controls,
      the chance of a false-positive association can be substantially increased if
      homozygotes for the putative high-risk allele are more common in the general
      population than predicted by Hardy-Weinberg Equilibrium. In contrast, Pearson's
      chi-square statistic can be conservative if the frequency of homozygotes for the
      high-risk allele is less than that predicted. A statistically valid method that
      corrects for deviations from Hardy-Weinberg Equilibrium is presented, so that the
      chance of a false-positive association is not greater than the acceptable level.

PMID- 10206618
TI  - Asymptotic bias and efficiency in case-control studies of candidate genes and
      gene-environment interactions: basic family designs.
AB  - Case-control designs that use population controls are compared with those that
      use controls selected from their relatives (i.e., siblings, cousins, or
      "pseudosibs" based on parental alleles) for estimating the effect of candidate
      genes and gene-environment interactions. The authors first evaluate the
      asymptotic bias in relative risk estimates resulting from using population
      controls when there is confounding due to population stratification. Using
      siblings or pseudosibs as controls completely addresses this issue, whereas
      cousins provide only partial protection from population stratification. Next,
      they show that the conventional conditional likelihood for matched case-control
      studies can give asymptotically biased effect estimates when applied to the
      pseudosib approach; the asymptotic bias is toward the null and disappears with
      disease rarity. They show how to reparameterize the pseudosib likelihood so this
      approach gives consistent effect estimates. They then show that the designs using
      population or pseudosib controls are generally the most efficient for estimating
      the main effect of a candidate gene, followed in efficiency by the design using
      cousins. Finally, they show that the design using sibling controls can be quite
      efficient when studying gene-environment interactions. In addition to asymptotic
      bias and efficiency issues, family-based designs might benefit from a higher
      motivation to participate among cases' relatives, but these designs have the
      disadvantage that many potential cases will be excluded from study by having no
      available controls.

PMID- 10206621
TI  - Nausea during pregnancy and congenital heart defects: a population-based case
      control study.
AB  - The authors investigated the possible association between a mother's nausea
      during pregnancy and her child's risk for a congenital heart defect using data
      from the population-based Atlanta Birth Defects Case-Control Study conducted in
      1982-1983. Case infants (n = 998) had nonsyndromic congenital heart defects and
      control infants (n = 3,029) had no congenital defects. Nausea during pregnancy
      (NP) was graded in eight levels of "severity" based on its onset, frequency, and
      duration. Level 1, the most severe NP, was associated with a lower risk for a
      congenital heart defect in the child (odds ratio (OR) = 0.81, 95% confidence
      interval (CI) 0.67-0.99) compared with no nausea. The lower risk tended to
      disappear with less severe levels of nausea, and the trend was statistically
      significant. Overall, early NP (levels 1 to 4 combined) with use of antinausea
      medication, particularly Bendectin (doxylamine, dicyclomine (dropped from the
      formulation in 1976), pyridoxine (vitamin B6)), was associated with a lower risk
      for congenital heart defects compared with: 1) absence of nausea (OR = 0.67, 95%
      CI 0.50-0.92), and 2) nausea without medication use (OR = 0.70, 95% CI 0.50
      0.94). The results suggest that pregnancy hormones and factors or, alternatively,
      a component of Bendectin (most probably pyridoxine) may be important for normal
      heart development. These findings outline potential areas for future research on
      and prevention of congenital heart defects.

PMID- 10206620
TI  - Chemical hair treatments and adverse pregnancy outcome among Black women in
      central North Carolina.
AB  - Several studies suggest that toxic chemicals in hair products may be absorbed
      through the scalp in sufficient amounts to increase the risks of adverse health
      effects in women or their infants. This case-control study of 525 Black women
      from three counties in North Carolina who had delivered a singleton, liveborn
      infant examined whether exposure to chemicals used in hair straightening and
      curling increased the odds that the infant was preterm or low birth weight. Cases
      consisted of 188 preterm and 156 low birth weight births (for 123 women, their
      infant was both low birth weight and preterm). Controls were 304 women who
      delivered term and normal birth weight infants. Women who used a chemical hair
      straightener at any time during pregnancy or within 3 months prior to conception
      had an adjusted odds ratios (OR) of 0.7 (95% confidence interval (CI) 0.4-1.1)
      for preterm birth and 0.6 (95% CI 0.4-1.1) for low birth weight. Exposure to
      chemical curl products was also not associated with preterm delivery (adjusted OR
      = 0.9, 95% CI 0.5-1.8) or low birth weight (adjusted OR = 1.0, 95% CI 0.5-1.9).
      Despite this failure to find an association, continued search for risk factors to
      which Black women are uniquely exposed is warranted.

PMID- 10206622
TI  - Birth weight and length as predictors for adult height.
AB  - Adult height has been found to be inversely associated with mortality. Recently,
      it has been suggested that growth in utero is linked with adult risk of several
      chronic diseases. The authors examined possible associations between birth
      weight, birth length, and adult height in young Danish men. They conducted the
      study in the fifth conscription district of Denmark including all the men born
      after January 1, 1973 who were residents in the study area during the period
      August 1, 1993 to July 31, 1994. The Danish Medical Birth Register contains
      information on all births in Denmark since January 1, 1973. Data on height from
      the Conscription Register were linked to the Danish Medical Birth Register in
      4,300 conscripts examined. Nearly all Danish men have to register with the draft
      board around age 18 years of age where they undergo a physical examination. There
      was a strong positive association between birth weight and adult height; for
      subjects with birth weight < or = 2,500 g, mean height was 175.7 cm, while for
      those with birth weight > or = 4,501 g, mean height was 184.1 cm. A positive
      association was also found between birth length and adult height. For subjects
      with birth length < 47 cm, mean adult height was 175.2 cm, increasing to 184.3 cm
      at birth length > 56 cm. The associations between birth length and adult height
      persisted after adjustment for birth weight, gestational age, and other
      confounders, while the associations between birth weight and adult height almost
      disappeared when adjusting for birth length and the same confounders. Genetic
      and/or environmental factors operating both during the pre- and postnatal period
      may be responsible for the association between birth length and adult height.

PMID- 10206623
TI  - Size at birth and blood pressure at 3 years of age. The Avon Longitudinal Study
      of Pregnancy and Childhood (ALSPAC).
AB  - The relations between size at birth and blood pressure were examined in a
      population-based longitudinal study of pregnancy and childbirth in the English
      county of Avon (the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC))
      in 1994-1996. A total of 1,860 singleton children aged 3 years (response rate =
      74%) were studied. Both height and body mass index were strongly related to blood
      pressure. After adjustment for current height and body mass index, birth weight
      showed a graded inverse relation with both systolic (-1.91 mmHg/kg, 95% CI -2.61
      to -1.21 mmHg/kg, p < 0.0001) and diastolic blood pressure (-1.42 mmHg/kg, 95% CI
      -1.96 to -0.88 mmHg/kg, p < 0.0001) which was similar in boys and girls. Although
      birth length, head circumference, and ponderal index at birth were also inversely
      related to blood pressure, these relations disappeared after adjustment for birth
      weight. The strength of the birth weight-blood pressure relation was not strongly
      influenced by maternal height or by weight gain in the first year after birth,
      but was particularly strong in children who were shortest at 3 years of age.
      While the association between birth weight and blood pressure is consistent with
      reports from many earlier studies, the absence of independent relations between
      other measures of size at birth (particularly length:head circumference and
      ponderal index) and blood pressure does not suggest that undernutrition at a
      critical period of fetal growth plays an important role. Moreover, accelerated
      postnatal growth does not seem to underlie the birth weight-blood pressure
      association.

PMID- 10206624
TI  - Lifetime low-level exposure to environmental lead and children's emotional and
      behavioral development at ages 11-13 years. The Port Pirie Cohort Study.
AB  - The Port Pirie Cohort Study is the first study to monitor prospectively the
      association between lifetime blood lead exposure and the prevalence of emotional
      and behavioral problems experienced by children. Lead exposure data along with
      ratings on the Child Behavior Checklist were obtained for 322 11-13-year-old
      children from the lead smelting community of Port Pirie, Australia. Mean total
      behavior problem score (95% confidence interval (CI)) for boys whose lifetime
      average blood lead concentration was above 15 microg/dl was 28.7 (24.6-32.8)
      compared with 21.1 (17.5-24.8) in boys with lower exposure levels. The
      corresponding mean scores (95% CI) for girls were 29.7 (25.3-34.2) and 18.0 (14.7
      21.3). After controlling for a number of confounding variables, including the
      quality of the child's HOME environment (assessed by Home Observation for
      Measurement of the Environment), maternal psychopathology, and the child's IQ,
      regression modeling predicted that for a hypothetical increase in lifetime blood
      lead exposure from 10 to 30 microg/dl, the externalizing behavior problem score
      would increase by 3.5 in boys (95% CI 1.6-5.4), and by 1.8 (95% CI -0.1 to 11.1)
      in girls. Internalizing behavior problem scores were predicted to rise by 2.1
      (95% CI 0.0-4.2) in girls but by only 0.8 (95% CI -0.9 to 2.4) in boys.

PMID- 10206625
TI  - Comparison of the entropy technique with two other techniques for detecting
      disease clustering using data from children with high blood lead levels.
AB  - The entropy technique was compared with two other case-control techniques for
      detecting disease clustering using data on blood lead levels of children who were
      patients at the King/Drew Medical Center in South-Central Los Angeles in 1991 to
      1994. The other two methods are the nearest neighbor technique (NNT) and Moran's
      IPOP technique, a variation of Moran's I test, in which rates are adjusted for
      population size. Four different blood lead levels (15 microg/dl, 20 microg/dl, 30
      microg/dl, 35 microg/dl) were used as cutoff levels to designate cases. Persons
      with blood lead levels greater than or equal to the cutoff level were designated
      as cases. The authors found significant clustering for all four cutoff levels
      using the entropy method, and for the first three cutoff levels using the NNT.
      They found significant clustering with Moran's IPOP for some scales for two of
      the cutoff levels. While performance of the entropy technique and the NNT were
      independent of scale, that of Moran's IPOP was highly scale-dependent.

PMID- 10206626
TI  - Petroleum distillate solvents as risk factors for undifferentiated connective
      tissue disease (UCTD).
AB  - Occupational solvent exposure may increase the risk of connective tissue disease
      (CTD). The objective of this case-control study was to investigate the relation
      between undifferentiated connective tissue disease (UCTD) and solvent exposure in
      Michigan and Ohio. Women were considered to have UCTD if they did not meet the
      American College of Rheumatology classification criteria for any CTD but had at
      least two documented signs, symptoms, or laboratory abnormalities suggestive of a
      CTD. Detailed information on solvent exposure was ascertained from 205 cases,
      diagnosed between 1980 and 1992, and 2,095 population-based controls. Age
      adjusted odds ratios (OR) and 95 percent confidence intervals (CI) were
      calculated for all exposures. Among 16 self-reported occupational activities with
      potential solvent exposure, furniture refinishing (OR = 9.73, 95 percent CI 1.48
      63.90), perfume, cosmetic, or drug manufacturing (OR = 7.71, 95 percent CI 2.24
      26.56), rubber product manufacturing (OR = 4.70, 95 percent CI 1.75-12.61), work
      in a medical diagnostic or pathology laboratory (OR = 4.52, 95 percent CI 2.27
      8.97), and painting or paint manufacturing (OR = 2.87, 95 percent CI 1.06-7.76)
      were significantly associated with UCTD. After expert review of self-reported
      exposure to ten specific solvents, paint thinners or removers (OR = 2.73, 95
      percent CI 1.80-4.16) and mineral spirits (OR = 1.81, 95 percent CI 1.09-3.02)
      were associated with UCTD. These results suggest that exposure to petroleum
      distillates increases the risk of developing UCTD.

PMID- 10206627
TI  - Temporal relation between Ixodes scapularis abundance and risk for Lyme disease
      associated with erythema migrans.
AB  - Understanding the role that nymphal and female ticks, Ixodes scapularis, have in
      the epidemiology of Lyme disease is essential to the development of successful
      prevention programs. In this study, the authors sought to evaluate the seasonal
      and annual relations between tick densities and patients > or = 16 years of age
      diagnosed with erythema migrans (EM), the rash associated with early Lyme
      disease. Ticks were collected weekly by drag sampling throughout most of the year
      from 1991 to 1996 in Westchester County, New York. The number of EM cases was
      based on patients diagnosed at the Westchester County Medical Center using
      Centers for Disease Control and Prevention (CDC) criteria. No patients with EM
      were diagnosed from January through April, when only adult ticks were active.
      Correlation analysis between monthly tick densities and EM incidence was
      significant for nymphs (r = 0.87, p < 0.01), but not for adult ticks (r = -0.57,
      p > 0.05). There was a strong, although not significant, correlation between peak
      annual number of patients with EM and peak nymphal tick abundance (r = 0.76, p =
      0.08). These data indicate that bites from adult I. scapularis only rarely result
      in Lyme disease, and that annual nymphal tick abundance determines exposure. This
      suggests that annual fluctuations in Lyme disease case numbers are largely due to
      natural changes in tick abundance and, therefore, that control of nymphal I.
      scapularis should be a major component of Lyme disease prevention efforts.

PMID- 10206629
TI  - Re: "Sudden infant death syndrome: risk factor profiles for distinct subgroups".

PMID- 10206628
TI  - Antibody levels to recombinant tick calreticulin increase in humans after
      exposure to Ixodes scapularis (Say) and are correlated with tick engorgement
      indices.
AB  - The antibody responses of subjects who presented with a definite Ixodes
      scapularis (Say) tick bite were measured to determine the utility of the antibody
      response against recombinant tick calreticulin (rTC) as a biologic marker of tick
      exposure. Subjects bitten by I. scapularis evidenced an increase in anti-rTC
      antibody levels between visit 1 and visit 2 from 24.3 to 27.1 ng/microl serum (n
      = 88, p = 0.003), and levels remained elevated at visit 3 (p = 0.005). These anti
      rTC antibody levels during visits 2 and 3 were significantly higher than those in
      four non-exposed controls. Tick engorgement indices, measured on the biting
      ticks, were found to be correlated with anti-rTC antibody levels (e.g., for visit
      3: Pearson's r = 0.357, p = 0.001). Tick engorgement index (TEI), ratio of body
      length to scutal width, was identified to be the only independent predictor of
      anti-rTC antibody levels in linear regression models. Logistic regression
      revealed that a bite from an I. scapularis tick that became engorged (TEI >3.4)
      was a risk factor for anti-rTC antibody seropositivity (adjusted odds ratio for
      age and bite location = 7.4 (95% confidence interval 2.1-26.4)). The anti-rTC
      antibody test had a sensitivity of 0.50 and a specificity of 0.86 for a bite from
      I. scapularis that became engorged. Immunoblotting revealed that subjects made a
      specific anti-rTC antibody response.

PMID- 10206630
TI  - Re: "Comments on a meta-analysis of the relation between dietary calcium intake
      and blood pressure".

PMID- 10206631
TI  - Re: "Cigarette smoking and the colorectal adenoma-carcinoma sequence: a
      hypothesis to explain the paradox".

PMID- 10206632
TI  - Japanese researcher faces US charges over data.

PMID- 10206633
TI  - Ethical failures block Los Angeles research.

PMID- 10206634
TI  - Primate study may yield new CJD clues...as researchers fume over blocked
      research.

PMID- 10206635
TI  - Brazilian scientists team up for cancer genome project.

PMID- 10206636
TI  - Grant agencies must be seen to be fair.

PMID- 10206637
TI  - Neurobiology. Slit, the midline repellent.

PMID- 10206638
TI  - Motor proteins. Another step ahead for myosin.

PMID- 10206639
TI  - Alzheimer's disease. In search of gamma-secretase.

PMID- 10206640
TI  - Cell biology. Boa constrictor or rattlesnake?

PMID- 10206641
TI  - Exposing the human nude phenotype.

PMID- 10206642
TI  - Seeing movement in the dark.

PMID- 10206643
TI  - Impairment of dynamin's GAP domain stimulates receptor-mediated endocytosis.
AB  - Dynamin is a GTP-hydrolysing protein that is an essential participant in clathrin
      mediated endocytosis by cells. It self-assembles into 'collars' in vitro which
      also formin vivo at the necks of invaginated coated pits. This self-assembly
      stimulates dynamin's GTPase activity and it has been proposed that dynamin
      hydrolyses GTP in order to generate the force needed to sever vesicles from the
      plasma membrane. A mechanism is now described in which self-assembly of dynamin
      is coordinated by a domain of dynamin with a GTPase-activating function.
      Unexpectedly, when dynamin mutants defective in self-assembly-stimulated GTPase
      activity are overexpressed, receptor-mediated endocytosis is accelerated. The
      results indicate that dynamin, like other members of the GTPase superfamily,
      functions as a molecular regulator in receptor-mediated endocytosis, rather than
      as a force-generating GTPase.

PMID- 10206644
TI  - Two transmembrane aspartates in presenilin-1 required for presenilin
      endoproteolysis and gamma-secretase activity.
AB  - Accumulation of the amyloid-beta protein (Abeta) in the cerebral cortex is an
      early and invariant event in the pathogenesis of Alzheimer's disease. The final
      step in the generation of Abeta from the beta-amyloid precursor protein is an
      apparently intramembranous proteolysis by the elusive gamma-secretase(s). The
      most common cause of familial Alzheimer's disease is mutation of the genes
      encoding presenilins 1 and 2, which alters gamma-secretase activity to increase
      the production of the highly amyloidogenic Abeta42 isoform. Moreover, deletion of
      presenilin-1 in mice greatly reduces gamma-secretase activity, indicating that
      presenilin-1 mediates most of this proteolytic event. Here we report that
      mutation of either of two conserved transmembrane (TM) aspartate residues in
      presenilin-1, Asp 257 (in TM6) and Asp 385 (in TM7), substantially reduces Abeta
      production and increases the amounts of the carboxy-terminal fragments of beta
      amyloid precursor protein that are the substrates of gamma-secretase. We observed
      these effects in three different cell lines as well as in cell-free microsomes.
      Either of the Asp --> Ala mutations also prevented the normal endoproteolysis of
      presenilin-1 in the TM6 --> TM7 cytoplasmic loop. In a functional presenilin-1
      variant (carrying a deletion in exon 9) that is associated with familial
      Alzheimer's disease and which does not require this cleavage, the Asp 385 --> Ala
      mutation still inhibited gamma-secretase activity. Our results indicate that the
      two transmembrane aspartate residues are critical for both presenilin-1
      endoproteolysis and gamma-secretase activity, and suggest that presenilin 1 is
      either a unique diaspartyl cofactor for gamma-secretase or is itself gamma
      secretase, an autoactivated intramembranous aspartyl protease.

PMID- 10206645
TI  - A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch
      intracellular domain.
AB  - Signalling through the receptor protein Notch, which is involved in crucial cell
      fate decisions during development, requires ligand-induced cleavage of Notch.
      This cleavage occurs within the predicted transmembrane domain, releasing the
      Notch intracellular domain (NICD), and is reminiscent of gamma-secretase-mediated
      cleavage of beta-amyloid precursor protein (APP), a critical event in the
      pathogenesis of Alzheimer's disease. A deficiency in presenilin-1 (PS1) inhibits
      processing of APP by gamma-secretase in mammalian cells, and genetic interactions
      between Notch and PS1 homologues in Caenorhabditis elegans indicate that the
      presenilins may modulate the Notch signalling pathway. Here we report that, in
      mammalian cells, PS1 deficiency also reduces the proteolytic release of NICD from
      a truncated Notch construct, thus identifying the specific biochemical step of
      the Notch signalling pathway that is affected by PS1. Moreover, several gamma
      secretase inhibitors block this same step in Notch processing, indicating that
      related protease activities are responsible for cleavage within the predicted
      transmembrane domains of Notch and APP. Thus the targeting of gamma-secretase for
      the treatment of Alzheimer's disease may risk toxicity caused by reduced Notch
      signalling.

PMID- 10206646
TI  - Presenilin is required for activity and nuclear access of Notch in Drosophila.
AB  - Presenilins are membrane proteins with multiple transmembrane domains that are
      thought to contribute to the development of Alzheimer's disease by affecting the
      processing of beta-amyloid precursor protein. Presenilins also facilitate the
      activity of transmembrane receptors of the LIN-12/Notch family. After ligand
      induced processing, the intracellular domain of LIN-12/Notch can enter the
      nucleus and participate in the transcriptional control of downstream target
      genes. Here we show that null mutations in the Drosophila Presenilin gene abolish
      Notch signal transduction and prevent its intracellular domain from entering the
      nucleus. Furthermore, we provide evidence that presenilin is required for the
      proteolytic release of the intracellular domain from the membrane following
      activation of Notch by ligand.

PMID- 10206647
TI  - Neurogenic phenotypes and altered Notch processing in Drosophila Presenilin
      mutants.
AB  - Presenilin proteins have been implicated both in developmental signalling by the
      cell-surface protein Notch and in the pathogenesis of Alzheimer's disease. Loss
      of presenilin function leads to Notch/lin-12-like mutant phenotypes in
      Caenorhabditis elegans and to reduced Notch1 expression in the mouse paraxial
      mesoderm. In humans, presenilins that are associated with Alzheimer's disease
      stimulate overproduction of the neurotoxic 42-amino-acid beta-amyloid derivative
      (Abeta42) of the amyloid-precursor protein APP. Here we describe loss-of-function
      mutations in the Drosophila Presenilin gene that cause lethal Notch-like
      phenotypes such as maternal neurogenic effects during embryogenesis, loss of
      lateral inhibition within proneural cell clusters, and absence of wing margin
      formation. We show that presenilin is required for the normal proteolytic
      production of carboxy-terminal Notch fragments that are needed for receptor
      maturation and signalling, and that genetically it acts upstream of both the
      membrane-bound form and the activated nuclear form of Notch. Our findings provide
      evidence for the existence of distinct processing sites or modifications in the
      extracellular domain of Notch. They also link the role of presenilin in Notch
      signalling to its effect on amyloid production in Alzheimer's disease.

PMID- 10206649
TI  - Structural basis for self-association and receptor recognition of human TRAF2.
AB  - Tumour necrosis factor (TNF)-receptor-associated factors (TRAFs) form a family of
      cytoplasmic adapter proteins that mediate signal transduction from many members
      of the TNF-receptor superfamily and the interleukin-1 receptor. They are
      important in the regulation of cell survival and cell death. The carboxy-terminal
      region of TRAFs (the TRAF domain) is required for self-association and
      interaction with receptors. The domain contains a predicted coiled-coil region
      that is followed by a highly conserved TRAF-C domain. Here we report the crystal
      structure of the TRAF domain of human TRAF2, both alone and in complex with a
      peptide from TNF receptor-2 (TNF-R2). The structures reveal a trimeric self
      association of the TRAF domain, which we confirm by studies in solution. The TRAF
      C domain forms a new, eight-stranded antiparallel beta-sandwich structure. The
      TNF-R2 peptide binds to a conserved shallow surface depression on one TRAF-C
      domain and does not contact the other protomers of the trimer. The nature of the
      interaction indicates that an SXXE motif may be a TRAF2-binding consensus
      sequence. The trimeric structure of the TRAF domain provides an avidity-based
      explanation for the dependence of TRAF recruitment on the oligomerization of the
      receptors by their trimeric extracellular ligands.

PMID- 10206648
TI  - The motor protein myosin-I produces its working stroke in two steps.
AB  - Many types of cellular motility, including muscle contraction, are driven by the
      cyclical interaction of the motor protein myosin with actin filaments, coupled to
      the breakdown of ATP. It is thought that myosin binds to actin and then produces
      force and movement as it 'tilts' or 'rocks' into one or more subsequent, stable
      conformations. Here we use an optical-tweezers transducer to measure the
      mechanical transitions made by a single myosin head while it is attached to
      actin. We find that two members of the myosin-I family, rat liver myosin-I of
      relative molecular mass 130,000 (M(r) 130K) and chick intestinal brush-border
      myosin-I, produce movement in two distinct steps. The initial movement (of
      roughly 6 nanometres) is produced within 10 milliseconds of actomyosin binding,
      and the second step (of roughly 5.5 nanometres) occurs after a variable time
      delay. The duration of the period following the second step is also variable and
      depends on the concentration of ATP. At the highest time resolution possible
      (about 1 millisecond), we cannot detect this second step when studying the single
      headed subfragment-1 of fast skeletal muscle myosin II. The slower kinetics of
      myosin-I have allowed us to observe the separate mechanical states that
      contribute to its working stroke.

PMID- 10206651
TI  - 7th Annual European Neurofibromatosis Meeting. Paris, France, December 5-6, 1997.
      Abstracts.

PMID- 10206650
TI  - Band-3 crosslinking-induced targeting of mouse carrier erythrocytes.
AB  - Mouse band-3 crosslinked carrier erythrocytes have been prepared. [125I]Carbonic
      anhydrase (CA) has been encapsulated into mouse erythrocytes. Then, loaded
      erythrocytes were labelled with 51Cr. Eventually, these doubly labelled cells
      were crosslinked with band-3 crosslinking reagents. [125I]CA was shown to have
      cytosolic localization in crosslinked carrier erythrocytes. Estimation of the
      action of band-3 crosslinkers on mouse carrier-erythrocyte membranes rendered
      values around 1721% of band-3 monomer reduction. Crosslinked carrier erythrocytes
      were in vivo targeted to liver, as shown by chromium-labelling localization.
      Also, encapsulated CA radioactivity was localized in vivo predominantly in liver,
      which is clearly in contrast with the behaviour shown by free CA injected into
      animals. These results support this model as a feasible system for the analysis
      of carrier-erythrocyte survival and targeting as well as the in vivo efficacy of
      release and targeting of encapsulated compounds.

PMID- 10206652
TI  - Psychosocial aspects of genetic testing for hereditary breast and/or ovarian
      cancer, 5th international meeting. Leuven, Belgium, June 29-30, 1998. Abstracts.

PMID- 10206653
TI  - Improvement of tylosin fermentation by mutation and medium optimization.
AB  - A tylosin-hyperproducing mutant of Streptomyces fradiae MNU20 was isolated from
      3500 strains obtained from either MNNG- or u.v.-treated S. fradiae NRRL2702. With
      the optimal medium, S. fradiae MNU20 was able to produce 159 mg tylosin g
      biomass(-1), indicating the tylosin productivity in S. fradiae NRLL2702 was
      increased 14-fold by mutation and medium optimization. When the effect of valine,
      succinate and natural zeolite on tylosin production was investigated sing the
      optimal medium, these substances essentially enhanced tylosin production up to
      349 mg g biomass(-1); their time addition during the culture period appeared to
      be critical for the increase.

PMID- 10206654
TI  - Detection and characterization of a bacteriocin produced by Lactococcus lactis
      subsp. cremoris R isolated from radish.

PMID- 10206655
TI  - In vivo and in vitro expression of human serum albumin genomic sequences in
      mammary epithelial cells with beta-lactoglobulin and whey acidic protein
      promoters.
AB  - The expression pattern of human serum albumin (HSA) in transgenic mice carrying
      various HSA genomic sequences driven either by the mouse whey acidic protein
      (WAP) or the sheep beta-lactoglobulin (BLG) promoters, was compared. The pattern
      of HSA expression in both WAP/HSA and BLG/HSA transgenic lines was copy number
      independent, and the major site of ectopic expression was the skeletal muscle.
      Although an equal proportion of expressors was determined in both sets of mice
      (approximately 25% secreting >0.1 mg/ml), the highest level of HSA secreted into
      the milk in the WAP/HSA transgenic lines was one order of magnitude lower than in
      the BLG/HSA lines. Despite this difference, the HSA expression patterns in the
      mammary gland were similar and consisted of two levels of variegated expression.
      Studies using mammary explant cultures revealed a comparable responsiveness to
      the lactogenic hormones insulin, hydrocortisone, and prolactin, although the
      WAP/HSA gene constructs were more sensitive to the hydrocortisone effect than
      were the BLG/HSA vectors. When HSA vectors were stably transfected into the mouse
      mammary cell line CID-9, they displayed a hierarchy of expression, dependent upon
      the specific complement of HSA introns included. Nevertheless, the expression of
      HSA in four out of five WAP/HSA constructs was similar to their BLG/HSA
      counterparts. This construct-dependent, and promoter-independent, hierarchy was
      also found following transfection into the newly established Golda-1 ovine
      mammary epithelial cell line.

PMID- 10206656
TI  - Nucleolar ultrastructure in bovine nuclear transfer embryos.
AB  - Nuclear transfer experiments in mammals have attempted to reprogram a donor
      nucleus to a state equivalent to the zygotic one. Reprogramming of the donor
      nucleus is, among other features, indicated by a synthesis of ribosomal RNA
      (rRNA). The initiation of rRNA synthesis is simultaneously reflected in nuclear
      morphology as a transformation of the nucleolus precursor body into a functional
      rRNA synthesising nucleolus with a characteristic ultrastructure. We examined
      nucleolar ultrastructure in bovine in vitro produced (control) embryos and in
      nuclear transfer embryos reconstructed from a MII phase (nonactivated) or S phase
      (activated) cytoplasts. Control embryos were fixed at the two-, four-, early
      eight- and late eight-cell stages; nuclear transfer embryos were fixed at 1 and 3
      hr post fusion and at the two-, four-, and eight-cell stages. Control embryos
      possessed a nucleolar precursor body throughout all three cell cycles. In the
      eight-cell stage embryo, a primary vacuole appeared as an electron lucid area
      originating in the centre of the nucleolar precursor body. In nuclear transfer
      embryos reconstructed from nonactivated cytoplasts, the nuclear envelope was
      fragmented or completely broken down at 1 hr after fusion and, by 3 hr after
      fusion, it was restored again. At this time, the reticulated fibrillo-granular
      nucleolus had an almost round shape. The nucleolar precursor body seen in the two
      cell stage nuclear transfer embryos consisted of intermingled filamentous
      components and secondary vacuoles. A nucleolar precursor body typical for the two
      cell stage control embryos was never observed. None of the reconstructed embryos
      of this group reached the eight-cell stage. Nuclear transfer embryos
      reconstructed from activated cytoplasts, in contrast, exhibited a complete
      nuclear envelope at all time intervals after fusion. In the two-cell stage
      nuclear transfer embryo, the originally reticulated nucleolus of the donor
      blastomere had changed into a typical nucleolar precursor body consisting of a
      homogeneous fibrillar structure. A primary vacuole appeared in the four-cell
      stage nuclear transfer embryos, which was one cell cycle earlier than in control
      embryos. Only nuclear transfer embryos reconstructed from activated cytoplasts
      underwent complete remodelling of the nucleolus. The reorganisation of the donor
      nucleolar architecture into a functionally active nucleolus was observed as early
      as in the four-cell stage nuclear transfer embryo. These ultrastructural
      observations were correlated with our autoradiographic data on the initiation of
      RNA synthesis in nuclear transfer embryos.

PMID- 10206657
TI  - Oxidation of gonadotrophin (PMSG) by oxygen free radicals alters its structure
      and hormonal activity.
AB  - The effect of oxygen free radicals produced by the Fenton reaction was used to
      induce oxidation and other structural changes in pregnant mare serum
      gonadotrophin (PMSG). Modifications in the spectrophotometric scan, an increase
      in exposed carbonyl groups, and the ability to reduce nitroblue tetrazolium, was
      achieved by the oxidized hormone when compared to the control PMSG. PMSG loses
      its biological activity when coming in contact with the free-radical generating
      system. This lack of activity is manifested as a loss of ovulation and a decrease
      in the weight of the ovaries and uterus. It was demonstrated that oxygen free
      radicals can induce structural and biological changes in the gonadotrophin.

PMID- 10206658
TI  - Immunolocalization of anti-agglutinin for spermatozoa in boars.
AB  - A boar "anti-agglutinin," which inhibits head-to-head agglutination of
      spermatozoa, has been identified as a 25-kDa sialoprotein contained in epididymal
      and seminal plasma. This study was conducted to determine the location of the
      anti-agglutinin on spermatozoa and in various organs, including epididymides, by
      indirect immunofluorescence and Western blotting techniques. Ejaculated boar
      spermatozoa were washed and subjected to immunocytochemical observation.
      Epididymal plasma was recovered from three different regions of epididymides and
      subjected to sodium dodecylsulfate (SDS)-polyacrylamide gel electrophoresis
      (PAGE) and Western blotting. Twelve kinds of organs (testis, epididymis, seminal
      vesicle, prostate, heart, liver, kidney, spleen, stomach, small intestine, lung,
      and muscle) were recovered from boars. The unilateral epididymides were fixed,
      cut into 10-microm frozen sections, and subjected to immunohistochemical
      observation. The other organs were homogenized and used for SDS-PAGE and Western
      blotting. Immunocytochemical observations revealed that the antiserum strongly
      recognized the acrosomal region and equatorial segment on unfixed and methanol
      fixed spermatozoa. Immunohistochemical observations revealed that the epithelia
      of the epididymal ducts were recognized by the antiserum mainly in the corpus
      epididymides. Moreover, the antiserum reacted with the luminal contents of the
      corpus and cauda epididymides. However, no specific reaction was detected in the
      caput epididymides. Western blotting showed that the antiserum selectively
      recognized a band of the anti-agglutinin in the corpus and cauda epididymal
      plasma, although no band was detected in the caput epididymal plasma. In the
      extracts from various organs, the single band was detected in the corpus and
      cauda epididymides at the same mobility as the anti-agglutinin, but not in the
      other organs. Based on these results, the following matters concerning the anti
      agglutinin are discussed: (1) the importance of its association with the acrosome
      of spermatozoa in inhibiting sperm head-to-head agglutination; (2) its origin in
      the epididymis; and (3) its tissue specificity.

PMID- 10206659
TI  - Human glucosamine-6-phosphate isomerase, a homologue of hamster oscillin, does
      not appear to be involved in Ca2+ release in mammalian oocytes.
AB  - Injections of cytosolic preparations from mammalian sperm into oocytes have been
      shown to trigger calcium [Ca2+]i oscillations and initiate activation of
      development. Recently, a protein isolated from hamster sperm has been suggested
      to be involved in the generation of these oscillations and it was named
      "oscillin." The human homologue of hamster oscillin is glucosamine 6-phosphate
      isomerase (GPI, EC no. 5.3.1.10), an enzyme so far described to be involved in
      hexose phosphate metabolism. To assess the role of GPI on Ca2+ signaling, a human
      recombinant protein was generated in a prokaryotic system and injected into fura
      2-dextran-loaded metaphase II (MII) mouse oocytes. Injection of recombinant GPI
      failed to induce Ca2+ responses in 12/12 injected MII oocytes despite the fact
      that the recombinant GPI was active as assessed by an enzymatic assay. Injection
      of buffer (0/6 oocytes) or fructose-6-phosphate, a product of GPI enzymatic
      reaction (0/5 oocytes), also failed to initiate Ca2+ responses. Conversely,
      injections of sperm cytosolic factor induced [Ca2+]i oscillations in all 17/17
      oocytes. In addition, injection of recombinant GPI or GPI mRNA failed to induce
      parthenogenetic activation (0/30 oocytes). Immunofluorescence studies using an
      anti-GPI polyclonal antibody (GK) resulted in localization of GPI to the sperm's
      equatorial region. Incubation of the GK antibody with sperm extracts failed to
      block the [Ca2+]i responses induced by these extracts. Moreover, near complete
      depletion of GPI from sperm fractions by immunoprecipitation did not impair the
      ability of these fractions to induce [Ca2+]i oscillations. In summary, our
      results support the role of a sperm cytosolic component(s) in the generation of
      [Ca2+]i oscillations during mammalian fertilization, although a protein other
      than GPI/oscillin is likely to be the active calcium releasing factor.

PMID- 10206660
TI  - Purification, characterization, and molecular cloning of carp hyosophorin.
AB  - Carp hyosophorin (HSP) is purified from oocytes. It is a highly glycosylated
      protein (10% protein and 90% carbohydrate) of high molecular weight (>100 kDa)
      and is localized in the cortical granules of oocytes. During cortical reaction
      carp HSP is exocytosed into the perivitelline space and is rapidly cleaved to the
      low-molecular-weight forms of 20 to 30 kDa. The major part of carp HSP cDNA is
      composed of tandem repeats, the repetitive domain. A repeat is 36 base pairs (bp)
      in length, which encodes 12 amino acid residues. The sequences of repeats vary
      within a given cDNA and among different cDNAs. The predominant sequences of
      repeats are DDGSGSNATTTQ. In addition, the length of the repetitive domain is
      highly variable among different genes and cDNAs, and ranges from 170 to 1,010 bp.
      Transcription of carp HSP is restricted in oocytes and starts very early during
      oogenesis. Carp HSP is highly species-specific. The RNA of goldfish ovary shows
      no positive signals when probed by carp HSP cDNA.

PMID- 10206661
TI  - Calcium and phospholipase A2 are both required for the acrosome reaction mediated
      by G-proteins stimulation in human spermatozoa.
AB  - G-proteins, calcium, and phospholipase A2 (PLA2) have all been implicated in the
      cascade of signaling events leading to the acrosome reaction in human
      spermatozoa. In order to study the role of Ca+2 and PLA2 during the acrosome
      reaction triggered by G-proteins, we treated human spermatozoa incubated for 3 hr
      under capacitating conditions with several reagents (GTPgammaS, A23187, ONO-RS
      082, arachidonic acid, BAPTA-AM, and TPEN), alone or in different combinations.
      Our results suggest that GTP-binding proteins require Ca+2 and PLA2 to accomplish
      their stimulatory effect, and that Ca+2 is also required when the acrosome
      reaction--bypassing the action of PLA2--is stimulated by AA. Accordingly, when
      treated with GTPgammaS or AA, the cells loaded with Fura 2-AM showed a steady
      increase of [Ca+2]i. On the other hand, a massive influx of Ca+2 was completely
      unable to induce the acrosome reaction if PLA2 was inhibited, suggesting that
      both an increase of [Ca+2]i and PLA2 activation are required for the acrosome
      reaction to occur.

PMID- 10206662
TI  - Cloning of complementary DNA encoding the pB1 component of the 54-kilodalton
      glycoprotein of boar seminal plasma.
AB  - Complementary DNA (cDNA) encoding a protein component pB1 (also pAIF-1 and DQH)
      of the 54-kilodalton glycoprotein of boar seminal plasma was cloned and its
      nucleotide sequence was determined (Gene Bank accession no. AF047026). The pB1
      precursor protein is a 130-amino-acid-long polypeptide containing a 25-amino-acid
      long signal peptide. The amino acid sequence of the pB1 is homologous to that of
      SFP1_BOVIN (named also BSP-A1/A2, PDC-109/ major protein and SVSp109), SFP3_BOVIN
      (BSP-A3), SFP4 BOVIN (BSP-30 KD), and SP1_HORSE (HSP-1) seminal plasma proteins.
      The homology extends also for the signal peptide of SFP1_BOVIN protein. All these
      seminal plasma proteins contain two fibronectin type-II domains that differ from
      those found in other proteins such as colagenases, fibronectins, and mannose
      receptors. The first domain located in the N-terminal region of pB1 is four amino
      acids shorter than those present in other proteins. High homology is also
      observed between 3' noncoding regions of the nucleotide sequences of cDNAs of
      pB1_PIG and SFP1_BOVIN (Gene Bank accession nos. AF047026 and P02784,
      respectively).

PMID- 10206663
TI  - MAP kinase activity is downregulated by phorbol ester during mouse oocyte
      maturation and egg activation in vitro.
AB  - The effects of protein kinase C (PKC) stimulator, phorbol 12-myriatate 13-acetate
      (PMA), on meiotic cell cycle regulation and mitogen-activated protein (MAP)
      kinase changes have been studied in mouse oocytes and eggs. The results showed
      that MAP kinase activation itself was not necessary for germinal vesicle
      breakdown (GVBD), but the ability of the ooplasm to phosphorylate MAP kinase was
      a prerequisite for this event. At concentrations of 1.6 nM, PMA effectively
      inhibited GVBD and MAP kinase activation, suggesting that PMA inhibits GVBD by
      inhibiting molecule(s) upstream to MAP kinase. At concentrations of 16.2 nM, PMA
      induced metaphase-interphase transition more effectively in eggs collected 19 hr
      after human chorionic gonadotropin (hCG) administration than in those collected
      15 hr after hCG administration. The degree of MAP kinase activity decrease was
      well correlated with the time course and proportion of pronuclear formation. On
      the other hand, when the effect of PMA on cell cycle progression was abolished by
      protein phosphatase inhibitor, okadaic acid, MAP kinase was superactivated. The
      biologically inactive 4 alpha-phorbol 12,13-didecanoate (4 alpha-PDD) had no
      evident effects on either GVBD and interphase transition or on MAP kinase
      activity. Furthermore, the effects of PMA on oocyte GVBD, egg activation, and MAP
      kinase activity could be overcome by the specific PKC inhibitor, calphostin C,
      suggesting the possible involvement of this enzyme in the regulation of MAP
      kinase activity. The results suggest that activation of PKC by PMA entrains a
      cascade of events that ultimately inhibits MAP kinase activation and GVBD in
      mouse oocytes and induces MAP kinase inactivation and metaphase-interphase
      transition in mouse eggs.

PMID- 10206664
TI  - An investigation of the latency period between sperm oolemmal adhesion and oocyte
      penetration.
AB  - In clinical studies of the ability of capacitated human sperm to penetrate zona
      free hamster eggs, we have previously observed that the ratio of oolemmal
      adherent to penetrating sperm varied between men. Sperm incorporation did not
      occur immediately following gamete adhesion and not all adherent sperm penetrated
      the egg. To further investigate this phenomenon, comparisons were made of the
      kinetics of gamete adhesion, membrane fusion, and sperm incorporation of
      capacitated mouse and human spermatozoa by zona-free hamster eggs and of mouse
      sperm by zona-free mouse and hamster eggs. Eggs were inseminated with either
      capacitated human or mouse sperm or combinations of both, washed out of sperm
      suspension after initial gamete adherence, and further incubated in sperm-free
      medium. Gamete membrane fusion was judged by dye transfer of Hoechst 33342 and
      sperm entry of the cortical ooplasm by observation of expanded sperm heads within
      acridine orange stained eggs. Oolemmal adherent mouse and human sperm fused with
      and penetrated zona-free hamster eggs at different times whether eggs were
      inseminated in parallel or with combinations of sperm of both species. Oolemmal
      adherent mouse sperm penetrated zona-free hamster eggs prior to their penetration
      of zona-free mouse eggs. Ultrastructural studies of zona-free human eggs
      inseminated with human sperm confirmed prior observations with hamster eggs that
      only acrosome-reacted human sperm adhere to the oolemma. These results have lead
      us to postulate that sperm entry into the egg may occur through a "zipper"
      mechanism involving the ligation of local gamete receptors similar to the
      incorporation of target particles by phagocytes and suggest that not all oolemmal
      adherent human sperm are capable of being incorporated although they have
      undergone an acrosome reaction.

PMID- 10206666
TI  - British Connective Tissue Society meeting. Cardiff, 30-31 March 1998. Abstracts.

PMID- 10206665
TI  - Regulation of microtubule sliding by a 36-kDa phosphoprotein in hamster sperm
      flagella.
AB  - Cyclic AMP has been shown essential for activation of sperm motility. When
      immotile hamster caudal epididymal spermatozoa were suspended in a Ca2+-deficient
      solution, they showed a sluggish motility. Spermatozoa were demembranated and
      transferred to an ATP-containing reactivation solution. Demembranated spermatozoa
      did not exhibit reactivated flagellar movement unless cAMP was added. Conversely,
      when the immotile epididymal spermatozoa were suspended in a Ca2+-containing
      solution, they were immediately activated to display a vigorous motility;
      demembranated spermatozoa also exhibited reactivated flagellar movement in the
      reactivation solution without cAMP. Further investigation of microtubule sliding
      properties revealed that the effects of Ca2+ on live spermatozoa were identical
      with the effects of cAMP on demembranated spermatozoa both in microtubule sliding
      velocity and sliding disintegration pattern. Moreover, a 36-kDa flagellar protein
      was found to be phosphorylated in a cAMP-dependent manner and coupled to the
      motility activation. A polyclonal antibody against this protein was developed and
      showed specific immunolocalization and significant inhibitory effects on
      microtubule sliding disintegration. These results indicate that extracellular
      Ca2+ owes its effect to triggering intracellular cAMP production, and cAMP
      dependent phosphorylation of a 36-kDa phosphoprotein activates hamster sperm
      motility through regulation of microtubule sliding properties.

PMID- 10206667
TI  - Determination of NA gene frequencies in the Spanish population by polymerase
      chain reaction with sequence-specific primers.
AB  - The granulocytic antigens NA1 and NA2 are two allelic gene products of the
      FcgammaRIIIB gene. These antigens are frequently targets of granulocytic-specific
      allo-antibodies and auto-antibodies that cause neutropenias. Different
      distributions of these antigens have been found in population studies. In our
      study, the genomic DNA of 345 healthy, unrelated Spanish individuals was typed
      for NA1 and NA2 using polymerase chain reaction (PCR) with sequence-specific
      primers (SSP). The gene frequencies found in the Spanish population were 0.29 for
      NA1 and 0.71 fo NA2. Flow cytometry immunotyping was also carried out in 20 of
      these samples, and an exact correlation was observed among the results. The gene
      frequencies determined in our study are similar to those reported in other
      Caucasian populations. The null phenotype reported in other serological studies
      was not found. This typing system can be used in population studies instead of
      serological tests as a more rapid, simple and reproducible method.

PMID- 10206668
TI  - Effects of microcystins on phosphorylase-a binding to phosphatase-2A: kinetic
      analysis by surface plasmon resonance biosensor.
AB  - Cyclic heptapeptide microcystins are a group of hepatoxicants which exert the
      cytotoxic effects by inhibiting the catalytic activities of phosphatase-2A (PP
      2A) and phosphatase-1 (PP-1) and thus disrupt the normal signal transduction
      pathways. Microcystins interact with PP-2A and PP-1 by a two-step mechanism
      involving rapid binding and inactivation of protein phosphatase catalytic
      subunit, followed by a slower covalent interaction. It was proposed that
      inactivation of PP-2A/PP-1 catalytic activity by microcystins precedes covalent
      adduct formation. In this study, we used a biosensor based on surface plasmon
      resonance (SPR) to examine the effects of three microcystins, MCLR, MCRR and
      MCYR, on the binding between PP-2A and its substrate, phosphorylase-a (PL-a),
      during the first step of the interaction. The SPR biosensor provides real-time
      information on the association and dissociation kinetics of PL-a with immobilized
      PP-2A in the absence and presence of microcystins. It was found that the affinity
      of PL-a to microcystin-bound PP-2A was four times smaller compared to unbound PP
      2A, due to 50% decreases in the association rates and two-fold increases in
      dissociation rates of PL-a binding to PP-2A. The results suggest that the rapid
      binding of microcystins to the PP-2A catalytic site leads to the formation of a
      noncovalent microcystin/PP-2A adduct. While the adduct formation fully inhibits
      the catalytic activity of PP-2A, it only results in partial inhibition of the
      substrate binding. The similar effects of the three microcystins on PP-2A suggest
      that the toxins bind to PP-2A at the same site and cause similar conformational
      changes. The present work also demonstrates the potential application of
      biosensor technology in environmental toxicological research.

PMID- 10206670
TI  - 1998 SSR Research Award.

PMID- 10206669
TI  - 1998 Carl G. Hartman Award.

PMID- 10206671
TI  - 1998 Distinguished Service Award.

PMID- 10206672
TI  - [Pleuro-pulmonary blastoma in the child].

PMID- 10206673
TI  - Report and papers arising from the 23rd annual meeting of the British Mass
      Spectrometry Society. University of Warwick, United Kingdom, 13-16 September
      1998.

PMID- 10206674
TI  - Oncogenes and cell proliferation.

PMID- 10206675
TI  - Oncogenes and cell proliferation. Web alert.

PMID- 10206676
TI  - Proceedings of European Seminars in Respiratory Medicine--Update 1998.
      Courmayeur, Italy, June 27-July 2, 1998.

PMID- 10206678
TI  - Two novel mutations of the arylsulfatase B gene in two Italian patients with
      severe form of mucopolysaccharidosis. Mutations in brief no. 127. Online.
AB  - Mucopolysaccharidosis type VI (MPS VI) or Maroteaux-Lamy syndrome, is a autosomal
      recessive disorder, due to the deficiency of the lysosomal enzyme N
      acetylgalactosamine-4-sulfatase (arylsufatase B, ASB: EC 3.1.6.12). Three
      classical forms of the disease have been differentiated: severe, intermediate,
      mild. Mutational analysis of the ASB gene resulted in the identification of 30
      ASB mutant alleles, each of which was found to be unique among unrelated
      patients, demonstrating a broad molecular heterogeneity of the disease. In this
      communication we present two novel mutant alleles in two severely affected
      subjects. Both alterations, the missense mutation G302R and the nonsense Q456X,
      were found in homozygosity and were confirmed by amplification refractory
      mutation system (ARMS) or restriction analysis. The missense G302R mutation
      concerns an amino acid which may be of special importance to the polypeptide,
      since 302 position is completely conserved in all the eukaryotic sulfatases
      aligned so far; the nonsense mutation Q456X leads to the translation of a
      putative mutant ASB protein lacking the last 78 amino acids with a loss of the 8
      kD mature polypeptide, one of the two peptides generated by intralysosomal
      proteolytic processing of the 64kD precursor.

PMID- 10206679
TI  - Novel allele of the insulin receptor substrate-1 bearing two non-conservative
      amino acid substitutions in a patient with noninsulin-dependent diabetes
      mellitus. Mutations in brief no. 130. Online.
AB  - We analyzed by SSCP the complete IRS-1 coding sequence in NIDDM patient #25 D.
      Unique conformers corresponding to a Ser to Tyr substitution at codon 1043
      (S1043Y), and to a Cys to Tyr substitution at codon 1095 (C1095Y) were detected
      in this patient. The results of sequential digestion with restriction enzymes
      indicated that the novel sequence variants segregate on the same allele.
      Relatives of patient #25 D were not available for study, to confirm segregation
      of the novel allele with NIDDM in the family. Several lines of evidence suggest
      that the non-conservative amino acid substitutions detected in NIDDM patient #25
      D have the potential to affect IRS-1 functions and could play a pathogenic role
      in this patient. Both S1043Y and C1095Y occur in a highly conserved sequence from
      human skeletal muscle, human hepatoma, mouse, and rat IRS-1. Protein subsequence
      analysis revealed that the S1043Y substitution abolishes a consensus sequence for
      glycogen synthase kinase 3 phosphorylation. Furthermore, S1043Y and C1095Y are
      not common IRS-1 polymorphisms as they were detected only in 1/136 choromosomes
      from NIDDM patients (allele frequency in NIDDM patients = 0.0007) and in 0/120
      chromosomes from control subjects.

PMID- 10206677
TI  - Double mutation (A171T and D444H) is a common cause of profound biotinidase
      deficiency in children ascertained by newborn screening the the United States.
      Mutations in brief no. 128. Online.
AB  - Biotinidase deficiency is inherited as an antosomal recessive trait that, unless
      treated with pharmacologic doses of biotin, can result in neurologic and
      cutaneous symptoms. We have identified two new mutations in exon D of the
      biotinidase gene of children with profound biotinidase deficiency ascertained by
      newborn screening. Transition 511G->A near the 5' end of exon D results in a
      substitution of threonine for alanine 171 (A171T) and transversion 1330G->C
      occurs close to the 3' end of exon D causing a substitution of histidine for
      aspartic acid 444 (D444H). The D444H mutation was detected in four individuals
      from our normal population whose mean serum biotinidase activity is 5.25
      nmol/min/ml, which is significantly lower than the mean normal activity (7.1
      nmol/min/ml). We calculated that this mutation causes a 52% loss of activity in
      the aberrant enzyme. Twenty-three individuals with the D444H mutation were found
      by allele specific oligonucleotide analysis of DNA from 296 randomly-selected,
      anonymous dried-blood spots. We estimate the frequency of this allele in the
      general population to be 0.039. In contrast, no individuals in 376 have the A171T
      mutation. Fourteen children (eleven probands and three siblings) out of the 31
      enzyme-deficient children have both the A171T and D444H mutations. Both mutations
      are inherited from a single parent as a double mutation allele. The nine families
      in which this allele was identified are of mostly European ancestry, although the
      mutation cannot be attributed to a specific nationality or ethnic group. The
      serum of a child who is homozygous for the double mutation allele has very little
      CRM and the aberrant enzyme has very low biotinylhydrolase activity and no
      botinyl-transferase activity. This double mutation allele (A171T and D444H) is a
      common cause of profound biotinidase deficience in children ascertained by
      newborn screening in the United States.

PMID- 10206680
TI  - A novel mutation (V191G) in a German-British type 1 Gaucher disease patient.
      Mutations in brief no. 131. Online.
AB  - Gaucher disease results from mutations in the glucocerebrosidase gene located on
      human chromosome 1q21. Three clinical forms of Gaucher disease have been
      described: type 1, nonneuropathic; type 2, acute neuropathic; and type 3,
      subacute neuropathic. We have identified a novel mutation in a German-British
      patient with type 1 Gaucher disease which results in V191G of the
      glucocerebrosidase polypeptide. Because the mutation abolishes a HphI cleavage
      site, its presence was confirmed by HphI RFLP analysis of PCR-amplified genomic
      DNA. In the second allele of the patient, the mutation identified was g.5841A
      G(N370S). Sequence analysis of the remainder of the coding region of the gene as
      well as the exon-intron boundaries showed identity to normal controls. Because
      mutation N370S has so far been found only in type 1 Gaucher disease and
      postulated to result in mild clinical presentation, and since the clinical course
      of this patient has been relatively mild with minimal skeletal involvement, we
      speculate that the V191G/N370S genotype may also result in good prognosis.

PMID- 10206681
TI  - alpha-Thalassaemia due to a single codon deletion in the alpha1-globin gene.
      Computational structural analysis of the new alpha-chain variant. Mutations in
      brief no. 132. Online.
AB  - A new unstable alpha-globin chain associated with alpha-thalassemia phenotype has
      been found in a Spanish patient. Molecular analysis of the alpha-globin gene
      complex using PCR and non-radioactive single-strand conformation analysis,
      allowed to identify a new mutation in the second exon of the alpha-globin gene.
      Direct sequencing of the abnormal fragment revealed a 3 bp deletion, which led to
      the loss of a single codon corresponding to a Lys (K) residue at position 60 or
      61 DK60 or DK61. Theoretical structural analysis, performed by computational
      methods, indicated that the loss of an amino acid residue at this position
      disturbed the contact region between the B and E-helices, affecting the overall
      stability of the molecule. Therefore, the DK60 and DK61 results in a structurally
      abnormal alpha-globin chain, not previously described, named Hb Clinic, which
      leads to the alpha-thalassemia phenotype in the heterozygote patient. No abnormal
      hemoglobin was detected by standard electrophoretic procedures, suggesting that
      this alpha-globin chain variant is so unstable that it may be catabolized
      immediately after its synthesis. This mutation was confirmed by PCR using an
      allele specific primer.

PMID- 10206682
TI  - Identification of cystic fibrosis mutations in the United Arab Emirates.
      Mutations in brief no. 133. Online.
AB  - We have designed a study aimed at identifying the genetic mutations responsible
      for cystic fibrosis (CF) in the population of the United Arab Emirates. The
      prevalence of CF in the UAE is at least 1/15,000 live births and the disease is
      associated with very severe clinical presentations. We have investigated 17
      unrelated families. Ten UAE national families were of Bedouin descent: all 15 CF
      patients, who presented with very severe forms of the disease, were homozygous
      for a S549R mutation due to a T->G transversion at nucleotide postion 1779.
      Amongst a distinct population of Baluch origin, CF patients from 6 out of 7
      affected families were DF508 homozyotes. Hence, the unique distribution of CF
      mutations in the United Arab Emirates--two mutations, S549R and DF508,
      characterize so far 94% of CF families--should allow efficient organizing and
      delivering of CF carrier screening programmes on the country's relatively limited
      population size.

PMID- 10206683
TI  - Identification of recurrent and novel mutations in the LDL receptor gene in
      Spanish patients with familial hypercholesterolemia. Mutations in brief no. 135.
      Online.
AB  - We used the single strand conformation polymorphism (SSCP) method to investigate
      13 apparently unrelated Spanish patients with familial hypercholesterolemia (FH)
      for mutations in the promoter region and the 18 exons and their flanking intron
      sequences of the low density lipoprotein (LDL) receptor gene. We found 16
      aberrant SSCP patterns, and the underlying mutations were characterized by DNA
      sequencing. Five novel missense mutations, Q71E, C74G, C95R, C281Y and D679E, and
      one nonsense mutation, Q133X, were identified. We also found six missense
      mutations, S156L, D200Y, D200G, E256K, T413K and C646Y, and one stop codon
      mutation, W(-18)X, that were previously described in patients from other
      populations. A new frameshift mutation, 2085del19, was found in one patient. We
      also identified three splicing mutations; two of them are novel mutations, 1706
      10G->A and 2390-1G->A, and the other one has been reported recently, 313+1G->C.
      Four patients were found to carry two different mutations in the same allele:
      Q71E and 313+1G->C; C95R and D679E; W(-18)X and E256K, and C281Y and 1706-10G->A.
      Our results demonstrate that there is a broad spectrum of mutations in the LDL
      receptor gene in the Spanish population.

PMID- 10206684
TI  - The identification of five novel mutations in the lysosomal acid a-(1-4)
      glucosidase gene from patients with glycogen storage disease type II. Mutations
      in brief no. 134. Online.
AB  - The autosomal recessive disorder Glycogen Storage Type II (GSDII) is caused by a
      deficiency in the lysosomal enzyme acid alpha-glucosidase. We have optimised a
      procedure to use fluorescent DNA sequencing technology to screen for mutations
      within the alpha-glucosidase gene from UK patients with GSDII. Five previously
      unknown mutations in six patients (4 early onset infantile and 2 late adult) have
      been found. The mutations are an insertion of a C residue in exon 2 (InsC258), an
      insertion of a G residue in exon 16 (InsG2242), a deletion of 20 nucleotides in
      exon 4 delta, and a nonsense mutation in exon 16 (G2237A-Trp746Stop). All will
      result in the introduction of a premature stop codon in the coding region,
      predicting a truncated and non-functional protein. The final mutation is a
      duplication of 18 nucleotides in exon 19 (Ins18nt2776) and will result in the
      insertion of an additional six amino acids into the protein chain after Asn925
      (Gly-Val-Pro-Val-Ser-Asn).

PMID- 10206686
TI  - Oral pathology and medicine in periodontics.

PMID- 10206685
TI  - The 1396del A mutation and a missense mutation or a rare polymorphism of the WRN
      gene detected in a French Werner family with a severe phenotype and a case of an
      unusual vulvar cancer. Mutations in brief no. 136. Online.
AB  - The Werner's syndrome (WS) is a rare recessive disease characterized by an early
      onset of geriatric disorders. The Werner's syndrome gene (WRN) recently cloned,
      encodes for an helicase and therefore plays a role in DNA metabolism and DNA
      repair. Here, we report the study of a French family with two affected members
      and numerous cancers. Using the protein truncation test and sequencing, we
      identified a homozygous mutation in the WRN gene. This mutation generates a frame
      shift leading to a very short 391 amino acids truncated protein without the
      helicase motif. A particularly severe phenotype of the affected patient was
      associated with an unusual vulvar cancer traditionaly observed in elderly
      patients and therefore likely to be related to the Werner's syndrome. An
      additional substitution of G for A at nucleotidic position 1392 was also
      described. We suggest that a relation between genotype and phenotype could exist
      in the studied family.

PMID- 10206687
TI  - Histones and histone-like DNA-binding proteins: correlations between structural
      differences, properties and functions.

PMID- 10206688
TI  - AFLP fingerprinting: an efficient technique for detecting genetic variation of
      Xanthomonas axonopodis pv. manihotis.
AB  - Xanthomonas axonopodis pv. manihotis (Xam) is the causative agent of cassava
      bacterial blight (CBB), a worldwide disease that is particularly destructive in
      South America and Africa. CBB is controlled essentially through the use of
      resistant varieties. To develop an appropriate disease management strategy, the
      genetic diversity of the pathogen's populations must be assessed. Until now, the
      genetic diversity of Xam was characterized by RFLP analyses using ribotyping, and
      plasmid and genomic Xam probes. We used AFLP (amplified fragment length
      polymorphism), a novel PCR-based technique, to characterize the genetic diversity
      of Colombian Xam isolates. Six Xam strains were tested with 65 AFLP primer
      combinations to identify the best selective primers. Eight primer combinations
      were selected according to their reproducibility, number of polymorphic bands and
      polymorphism detected between Xam strains. Forty-seven Xam strains, originating
      from different Colombian ecozones, were analysed with the selected combinations.
      Results obtained with AFLP are consistent with those obtained with RFLP, using
      plasmid DNA as a probe. Some primer combinations differentiated Xam strains that
      were not distinguished by RFLP analyses, thus AFLP fingerprinting allowed a
      better definition of the genetic relationships between Xam strains.

PMID- 10206689
TI  - Structure and function of a cysBJIH gene cluster in the purple sulphur bacterium
      Thiocapsa roseopersicina.
AB  - A gene cluster containing homologues of the genes cysB, cysJI and cysH was found
      in the genome of the sulphur-oxidizing purple bacterium Thiocapsa roseopersicina.
      The nucleotide sequence indicated four open reading frames encoding homologues of
      3'-phosphoadenylylsulphate (PAPS) reductase (CysH), sulphite reductase
      flavoprotein (CysJ) and haem protein (CysI) subunits, and a transcriptional
      regulator (CysB). Genes cysJIH are separated by a short cis-active intergenic
      region from cysB which is transcribed divergently. cysB encodes a polypeptide of
      35.9 kDa consisting of 323 amino acid residues with 40% identity to the CysB
      regulator from enterobacteria. cysH encodes a protein with 239 amino acid
      residues and a calculated mass of 27.7 kDa; cysJ encodes a protein with 522 amino
      acid residues and a mass of 57.8 kDa; and cysI encodes a protein with 559 amino
      acid residues and a mass of 62.3 kDa. The cysJIH gene products have been
      expressed and used for complementation of cys mutants from Escherichia coli
      Biochemical analysis. The gene product CysH is a thioredoxin-dependent PAPS
      reductase (EC 1.8.99.4). It was repressed under photoautotrophic growth using
      hydrogen sulphide as electron donor and derepressed under conditions of sulphate
      deficiency. Products of the cysJI genes were identified as the two subunits of
      NADPH-sulphite reductase (EC 1.8.1.2). cysJ encoded the flavoprotein, with > or =
      39% identity to the protein from E. coli, and cysI encoded the haem protein, with
      > or = 53% identity. A cysI clone was used to complement the corresponding mutant
      from E. coli and to express enzymically active methylviologen-sulphite reductase.

PMID- 10206690
TI  - Structural and functional analysis of pCI65st, a 6.5 kb plasmid from
      Streptococcus thermophilus NDI-6.
AB  - The 6.5 kb cryptic plasmid pCI65st from Streptococcus thermophilus NDI-6, a
      strain isolated from the Indian fermented milk dahi, was subcloned and sequenced.
      Five putative ORFs were identified. ORF1 could encode a 315 aa polypeptide almost
      identical to the RepA protein of previously sequenced S. thermophilus plasmids,
      indicating that pCI65st is one of the pC194 group of small gram-positive rolling
      circle plasmids. ORFs 2 and 4 were virtually identical and could specify proteins
      of approximately 150 aa with significant similarity to the small heat-shock
      proteins described from a variety of gram-positive bacteria. ORF3 could encode a
      415 aa protein similar to enolase, an enzyme involved in glycolysis and
      gluconeogenesis. ORF5 could encode a 412 aa protein which had high similarity to
      the HsdS (specificity) proteins of type I restriction-modification systems.
      Variants of strain NDI-6 which lacked pCI65st were readily isolated after
      subculture of the parent strain at 32 degrees C. The plasmid-bearing parent
      culture was significantly more resistant to a temperature shift from 42 degrees C
      to 62 degrees C than its plasmid-free variant and expressed proteins which
      corresponded with the predicted translation products from ORF2 and ORF4. In
      addition, plasmid-free mutants were lysed in broth by bacteriophages to which the
      parent culture was resistant.

PMID- 10206691
TI  - A dispensable region of the chromosome which is associated with an avirulence
      gene in Pseudomonas syringae pv. pisi.
AB  - Pseudomonas syringae pv. pisi comprises a number of races which fall into two
      phylogenetically distinct groups (designated I and II). Races are based on
      cultivar specificity in the host plant, pea (Pisum sativum), and are specified by
      the presence of avirulence genes. The avirulence gene avrPpiA1 is present on the
      chromosome of all strains examined in race 2, which belongs to phylogenetic group
      II. A race 4B strain, from phylogenetic group I, lacks this avirulence gene and a
      comparative study was made of the chromosome in strains representing these two
      races. A race 2 cosmid clone (pAV270) carrying avrPpiA1 was used as a basis for
      collinearity analysis of races 2 and 4B. A region of the chromosome amounting to
      8.5 kb and including avrPpiA1 was absent from race 4B compared with race 2. A
      fragment spanning the junction of the discontinuity in race 4B was isolated,
      cloned and used to delimit the extent of the additional DNA present in race 2. In
      both races the borders of the discontinuity contained DNA sequences which showed
      a high degree of conservation. A 7 bp slightly imperfect direct repeat
      (CCAGC(T)/(A)T) flanked the additional DNA in race 2, with a single copy in race
      4B. The region flanking the additional DNA was present in all races of P.
      syringae pv. pisi. These results confirm the phylogenetic groupings in P.
      syringae pv. pisi.

PMID- 10206692
TI  - Expression and characterization of the prtV gene encoding a collagenase from
      Vibrio parahaemolyticus in Escherichia coli.
AB  - The prtV gene, encoding a collagenase of Vibrio parahaemolyticus, was expressed
      in Escherichia coli and purified by affinity chromatography. The transformant E.
      coli BL21(DE3)(pPRT2) secreted the recombinant PrtV, and the highest enzyme
      activity was detected in the culture supernatant after 5 h IPTG induction. The
      molecular mass of purified PrtV was 62 kDa as determined by gel filtration, which
      was similar to that obtained by SDS-PAGE (64 kDa). This suggested that PrtV was a
      monomer protein having no subunit structure. The isoelectric point of PrtV was
      8.52. In addition, PrtV contained a 27 amino acid signal peptide, and the amino
      acid composition of the PrtV showed satisfactory agreement with that predicted
      from the DNA sequence. The optimum temperature and pH of PrtV were 40 degrees C
      and pH 7.5, respectively. The activity of PrtV was inhibited by chelators such as
      EDTA, EGTA and 1,10-phenanthroline; however, its activity was restored by the
      addition of various metal ions (Co2+, Mn2+, Ca2+, Cu2+, Ni2+ and Zn2+),
      indicating that PrtV is a metalloprotease. PrtV degraded both type I collagen and
      synthetic substrate FALGPA well, showing that PrtV is indeed a collagenase.

PMID- 10206693
TI  - The medium-/long-chain fatty acyl-CoA dehydrogenase (fadF) gene of Salmonella
      typhimurium is a phase 1 starvation-stress response (SSR) locus.
AB  - Salmonella enterica serovar Typhimurium (S. typhimurium) is an enteric pathogen
      that causes significant morbidity in humans and other mammals. During their life
      cycle, salmonellae must survive frequent exposures to a variety of environmental
      stresses, e.g. carbon-source (C) starvation. The starvation-stress response (SSR)
      of S. typhimurium encompasses the genetic and physiological realignments that
      occur when an essential nutrient becomes limiting for bacterial growth. The
      function of the SSR is to produce a cell capable of surviving long-term
      starvation. This paper reports that three C-starvation-inducible lac fusions from
      an S. typhimurium C-starvation-inducible lac fusion library are all within a gene
      identified as fadF, which encodes an acyl-CoA dehydrogenase (ACDH) specific for
      medium-/long-chain fatty acids. This identification is supported by several
      findings: (a) significant homology at the amino acid sequence level with the ACDH
      enzymes from other bacteria and eukaryotes, (b) undetectable beta-oxidation
      levels in fadF insertion mutants, (c) inability of fad insertion mutants to grow
      on oleate or decanoate as a sole C-source, and (d) inducibility of fadF::lac
      fusions by the long-chain fatty acid oleate. In addition, the results indicate
      that the C-starvation-induction of fadF is under negative control by the FadR
      global regulator and positive control by the cAMP:cAMP receptor protein complex
      and ppGpp. It is also shown that the fadF locus is important for C-starvation
      survival in S. typhimurium. Furthermore, the results demonstrate that fadF is
      induced within cultured Madin-Darby canine kidney (MDCK) epithelial cells,
      suggesting that signals for its induction (C-starvation and/or long-chain fatty
      acids) may be present in the intracellular environment encountered by S.
      typhimurium. However, fadF insertion mutations did not have an overt effect on
      mouse virulence.

PMID- 10206694
TI  - Structure and transcriptional regulation of the gene encoding pyruvate formate
      lyase of a ruminal bacterium, Streptococcus bovis.
AB  - The gene (pfl) encoding pyruvate formate-lyase (Pfl) from Streptococcus bovis was
      sequenced. The deduced amino acid sequence of Pfl was similar to Streptococcus
      mutans Pfl, and included the conserved regions necessary for free-radical
      formation and a catalytic site. The Pfl of S. bovis appeared to be a free-radical
      containing enzyme because of its dioxygen sensitivity and its amino acid sequence
      similarity with the Escherichia coli enzyme. The pfl mRNA of S. bovis was
      approximately 2.3 kb and was transcribed in a monocistronic fashion. When cells
      were grown in batch culture at pH 6.9, the level of pfl transcript increased as
      the growth phase changed from exponential growth to stationary phase. This result
      was in constrast to the previous observation that the level of lactate
      dehydrogenase (Ldh) mRNA decreased during the later stages of growth. Continuous
      culture experiments conducted at pH 6.9 under glucose-limited and ammonia-limited
      conditions revealed that pfl mRNA was decreased by an excess supply of glucose,
      as well as by a high growth rate. On the contrary, ldh mRNA increased when excess
      glucose was supplied and the growth rate was high. The amount of pfl mRNA in
      cells was lower at pH 4.5 than pH 6.9, whereas the level of ldh mRNA was higher
      at pH 4.5. This result was consistent with the amounts of Pfl and Ldh in cells
      and the proportion of formate and lactate produced. These results support the
      hypothesis that S. bovis regulates Pfl and Ldh synthesis at the transcriptional
      level in response to growth conditions.

PMID- 10206695
TI  - A low-molecular-mass protein from Methylococcus capsulatus (Bath) is responsible
      for the regulation of formaldehyde dehydrogenase activity in vitro.
AB  - An 8.6 kDa protein, which the authors call a modifin, has been purified from
      Methylococcus capsulatus (Bath) and has been shown to alter the substrate
      specificity and kinetics of NAD+-linked formaldehyde dehydrogenase (FDH) isolated
      from the same organism. Purification methods for both the modifin and FDH are
      presented which reliably produced pure protein for further analysis. Analysis of
      the molecular mass and N-terminal sequence of both FDH and the modifin indicate
      that they are unique proteins and show no similarity to alcohol or aldehyde
      dehydrogenase enzymes isolated from methylotrophic bacteria. Substrate
      specificity studies demonstrated that FDH oxidized formaldehyde exclusively in
      the presence of the modifin; a diverse range of aldehydes and alcohols were
      oxidized by FDH in the absence of the modifin. No formaldehyde oxidation was
      detected in the absence of the modifin. Attempts to replace the modifin with
      glutathione or high concentrations of methanol to stimulate formaldehyde
      oxidation failed. With acetaldehyde as substrate, FDH showed standard Michaelis
      Menten kinetics; interaction of FDH with the modifin using formaldehyde as
      substrate altered the kinetics of the reaction to sigmoidal. Kinetic analysis
      during turnover experiments indicated that the FDH may be associated with bound
      formaldehyde following enzyme isolation and that NAD may also be associated with
      the enzyme but in a form that is less tightly bound than found with the methanol
      dehydrogenase from Bacillus methanolicus. Data are presented which indicate that
      the modifin may play an important role in regulating formaldehyde concentration
      in vivo.

PMID- 10206696
TI  - Partial characterization of a major autolysin from Mycobacterium phlei.
AB  - Autolytic enzyme profiles of fast- and slow-growing mycobacteria were examined
      using SDS-PAGE zymography with incorporated mycobacterial peptidoglycan sacculi
      as substrate. Each species tested (Mycobacterium phlei, Mycobacterium smegmatis,
      Mycobacterium aurum, Mycobacterium fortuitum and Mycobacterium kansasii) appeared
      to produce a different set of enzymes on the basis of differing number and
      molecular masses. A major autolysin from M. phlei was purified to apparent
      homogeneity by DEAE-cellulose chromatography, preparative gel electrophoresis and
      Mono Q FPLC. This enzyme had an estimated molecular mass of 38 kDa, an
      isoelectric point of 5.5 and a pH optimum of pH 7.5. Digestion of purified
      peptidoglycan by the enzyme resulted in the appearance of reducing sugars,
      suggesting that the 38 kDa autolysin is a beta-glycosidase. Partial internal
      amino acid sequence of the autolysin was determined and should facilitate
      identification, cloning and overexpression of the encoding gene.

PMID- 10206697
TI  - Staphylococcus aureus expresses a cell surface protein that binds both IgG and
      beta2-glycoprotein I.
AB  - The existence of a second IgG-binding protein, protein Sbi, in Staphylococcus
      aureus has been reported previously. Later data indicated that protein Sbi also
      bound another serum component. This component has now been affinity-purified on
      immobilized protein Sbi and identified as beta2-glycoprotein I (beta2-GPI), also
      known as apolipoprotein H. The minimal beta2-GPI-binding domain was identified by
      shotgun phage display and the binding was shown to be mediated by a region of 57
      amino acids, clearly separated from the IgG-binding domain. It is also shown that
      protein Sbi, and thus the beta2-GPI-binding activity, is expressed on the
      staphylococcal cell surface at levels varying between strains.

PMID- 10206698
TI  - Identification of protease and rpoN-associated genes of uropathogenic Proteus
      mirabilis by negative selection in a mouse model of ascending urinary tract
      infection.
AB  - Proteus mirabilis, a motile gram-negative bacterium, is a principal cause of
      urinary tract infections in patients with functional or anatomical abnormalities
      of the urinary tract or those with urinary catheters in place. Thus far,
      virulence factors including urease, flagella, haemolysin, various fimbriae, IgA
      protease and a deaminase have been characterized based on the phenotypic traits
      conferred by these proteins. In this study, an attempt was made to identify new
      virulence genes of P. mirabilis that may not have identifiable phenotypes using
      the recently described technique of signature-tagged mutagenesis. A pool of
      chromosomal transposon mutants was made through conjugation and
      kanamycin/tetracycline selection; random insertion was confirmed by Southern
      blotting of chromosomal DNA isolated from 16 mutants using the aphA gene as a
      probe. From the total pool, 2.3% (9/397) auxotrophic mutants and 3.5% (14/397)
      swarming mutants were identified by screening on minimal salts agar and Luria
      agar plates, respectively. Thirty per cent of the mutants, found to have either
      no tag or an unamplifiable tag, were removed from the input pool. Then 10(7)
      c.f.u. from a 96-mutant pool (approximately 10(5) c.f.u. of each mutant) were
      used as an input pool to transurethrally inoculate seven CBA mice. After 2 d
      infection, bacteria were recovered from the bladders and kidneys and yielded
      about 10(5) c.f.u. as an output pool. Dot blot analysis showed that two of the 96
      mutants, designated B2 and B5, could not be hybridized by signature tags
      amplified from the bladder output pool. Interrupted genes from these two mutants
      were cloned and sequenced. The interrupted gene in B2 predicts a polypeptide of
      37.3 kDa that shares amino acid similarity with a putative protease or
      collagenase precursor. The gene in B5 predicts a polypeptide of 32.6 kDa that is
      very similar to that encoded by ORF284 of the rpoN operon controlling expression
      of nitrogen-regulated genes from several bacterial species. The virulence of the
      two mutants was tested further by co-challenging CBA mice with each mutant and
      the parental strain. After 1 week of infection, the B2 and B5 mutants were
      recovered in numbers 100-fold and 1000-fold less than the parental strain,
      respectively. Using an in vitro assay, it was shown that the B2 mutant had
      significantly less (P = 0.0001) extracellular protease activity than the wild
      type strain. These findings demonstrate that signature-tagged mutagenesis is a
      viable approach to identify bacterial genes associated with the ability to infect
      the urinary tract.

PMID- 10206700
TI  - rDNA spacer rearrangements and concerted evolution.

PMID- 10206699
TI  - The haemin storage (Hms+) phenotype of Yersinia pestis is not essential for the
      pathogenesis of bubonic plague in mammals.
AB  - The haemin storage (Hms+) phenotype of Yersinia pestis enables this bacillus to
      form greenish/brown or red colonies on haemin or Congo Red agar plates,
      respectively, at 26 but not 37 degrees C. Escherichia coli strains that contain
      mutations in genes essential for siderophore biosynthesis, porphyrin generation
      and/or haemin transport remain unable to utilize exogenous haemin as a
      nutritional iron or porphyrin source when transformed with the cloned Y. pestis
      hmsHFRS locus. Further physiological analysis of the Hms+ phenotype of Y. pestis
      strain KIM6+ suggests that the haemin and inorganic iron stored by the Hms system
      was not used nutritionally under subsequent iron-deficient conditions. In vitro
      analysis of the bactericidal effects of hydrogen peroxide, superoxide and nitric
      oxide showed that Hms- Y. pestis cells, in certain cases, were more susceptible
      than the Hms+ parent cells to these reactive oxygen species at 26 and/or 37
      degrees C. In adherence assays, a higher percentage of Hms+ cells were associated
      with HeLa cells and normal human neutrophils, compared to Hms- cells. However,
      the Hms+ phenotype did not provide any additional protection against the killing
      effects of neutrophils. Finally, LD50 analysis in subcutaneously infected mice
      showed that an Hms- strain was slightly more virulent than Hms+, indicating that
      the Hms phenotype is not essential for the pathogenesis of bubonic plague in
      mammals.

PMID- 10206701
TI  - Pseudomonas aeruginosa outer-membrane protein F epitopes are highly immunogenic
      in mice when expressed on a plant virus.
AB  - A synthetic peptide (peptide 10) representing a surface-exposed, linear B cell
      epitope from outer-membrane (OM) protein F of Pseudomonas aeruginosa was shown
      previously to afford protection in mice from P. aeruginosa infection. This
      peptide was expressed in tandem with the protein F peptide 18 on each of the two
      coat proteins of cowpea mosaic virus (CPMV). The chimaeric virus particles (CVPs)
      expressing the peptides on the S (small) coat protein (CPMV-PAE4) and L (large)
      coat protein (CPMV-PAE5) were used to immunize mice. Following subcutaneous
      immunization in Freund's and QuilA adjuvants, CPMV-PAE4 induced antibodies
      predominantly against peptide 18, whereas CPMV-PAE5 produced antibodies
      exclusively against peptide 10, indicating that the site of peptide expression on
      CPMV influences its immune recognition. The anti-peptide antibodies elicited by
      CPMV-PAE5 were predominantly of the IgG2a isotype, indicating a highly polarized
      TH1-type response. The peptide-specific IgG2a strongly recognized the whole F
      protein, but more importantly, recognized protein F in all seven Fisher-Devlin
      immunotypes of P. aeruginosa. Furthermore, the peptide-specific IgG2a in CVP/QS
      21 adjuvant-immunized mice was shown to bind complement and to augment
      phagocytosis of P. aeruginosa by human neutrophils in vitro. The ability of CPMV
      PAE5 to induce P. aeruginosa-specific opsonic IgG2a gives it potential for
      further development as a protective vaccine against P. aeruginosa.

PMID- 10206703
TI  - Stress induction of HSP30, the plasma membrane heat shock protein gene of
      Saccharomyces cerevisiae, appears not to use known stress-regulated transcription
      factors.
AB  - More than one transcription factor contributes to the Saccharomyces cerevisiae
      heat shock response. Many genes are induced through the activation of heat shock
      factor (Hsf1), a protein that is constitutively bound to heat shock promoter
      elements (HSEs). Other genes are switched on by Msn2/Msn4-dependent activation of
      a quite separate promoter element (the stress response element, STRE). While Hsf
      directs gene activation mainly in response to heat stress, STRE-directed
      transcription is stimulated not only by heat but also by several other stresses,
      starvation included. HSP30, encoding the plasma membrane heat shock protein, is
      shown in this study to be activated by several stresses. It is most strongly
      induced with heat shock, ethanol and weak organic acid exposure. The HSP30
      promoter has no good agreement to the HSE consensus and its stress activation is
      unaffected by a mutation (hsf1-m3) that causes defective heat shock activation of
      Hsf1-dependent genes. Activation of HSP30 occurs with some, but not all, STRE
      inducing stresses and is largely unaffected either by loss of the Msn2/Msn4
      transcription factors or with mutation of all STRE-like consensus sequences of
      the promoter. Stress activation of HSP30 appears therefore to involve as yet
      unidentified components of the yeast transcriptional apparatus.

PMID- 10206702
TI  - Expression of disulphide-bridge-dependent conformational epitopes and
      immunogenicity of the carboxy-terminal 19 kDa domain of Plasmodium yoelii
      merozoite surface protein-1 in live attenuated Salmonella vaccine strains.
AB  - The 19 kDa carboxy-terminal domain of Plasmodium yoelii merozoite surface protein
      1 (MSP1(19)) was expressed in Salmonella vaccine strains as a carboxy-terminal
      fusion to fragment C of tetanus toxin (TetC). This study demonstrates that
      antibodies that recognize disulphide-dependent conformational epitopes in native
      MSP1 react with the TetC-MSP1(19) fusion protein expressed in Salmonella. The
      proper folding of MSP1(19) polypeptide is dependent on both the Salmonella host
      strain and the protein to which the MSP1(19) polypeptide is fused. Serum from
      mice immunized with Salmonella typhimurium C5aroD expressing TetC-MSP1(19)
      recognized native MSP1 as shown by immunofluorescence with P. yoelii-infected
      erythrocytes. Antibody levels to MSP1(19) were highest in out-bred mice immunized
      with S. typhimurium C5aroD carrying pTECH2-MSP1(19) and antibody was mostly
      directed against reduction-sensitive conformational epitopes. However, antibody
      levels were lower than in BALB/c mice immunized with a glutathione S-transferase
      (GST)-MSP1(19) fusion protein in Freund's adjuvant, and which were protected
      against P. yoelii challenge infection. In challenge experiments with P. yoelii
      the Salmonella-immunized mice were not protected, probably reflecting the
      magnitude of the antibody response. The results of this study have important
      implications in the design of live multivalent bacterial vaccines against
      eukaryotic pathogens.

PMID- 10206704
TI  - Two putative MAP kinase genes, ZrHOG1 and ZrHOG2, cloned from the salt-tolerant
      yeast Zygosaccharomyces rouxii are functionally homologous to the Saccharomyces
      cerevisiae HOG1 gene.
AB  - The salt-tolerant yeast Zygosaccharomyces rouxii can adjust its osmotic balance
      when responding to osmotic shock by accumulating glycerol as the compatible
      osmolyte. However, the mechanism of glycerol production in Z. rouxii cells and
      its genetic regulation remain to be elucidated. Two putative mitogen-activated
      protein (MAP) kinase genes, ZrHOG1 and ZrHOG2, were cloned from Z. rouxii by
      their homology with HOG1 from Saccharomyces cerevisiae. The deduced amino acid
      sequences of ZrHog1p and ZrHog2p indicated close homology to that of Hog1p and
      contained a TGY motif for phosphorylation by MAP kinase kinase. When ZrHOG1 or
      ZrHOG2 was expressed in an S. cerevisiae hog1delta null mutant, the salt
      tolerance and osmotic tolerance characteristics of wild-type S. cerevisiae were
      restored. In addition, the aberrant cell morphology and low glycerol content of
      the hog1delta null mutant were corrected, indicating that ZrHog1p and ZrHog2p
      have functions similar to Hog1p. While the transcription of the glycerol-3
      phosphate dehydrogenase gene (GPD1) of the ZrHOG1-harbouring S. cerevisiae mutant
      was similar to that of wild-type S. cerevisiae, the ZrHOG2-harbouring strain
      showed prolonged GPD1 transcription. Both Zrhog1delta and Zrhog2delta Z. rouxii
      null mutants showed a decrease in salt tolerance compared to the wild-type
      strain. The present study suggested the presence of a high-osmolarity glycerol
      response (HOG) pathway in Z. rouxii similar to that elucidated in S. cerevisiae.
      Two putative MAP kinase genes in Z. rouxii appeared to be significant in either
      osmotic regulation or ion homeostasis.

PMID- 10206706
TI  - Distribution of chitinase in guinea pig tissues and increases in levels of this
      enzyme after systemic infection with Aspergillus fumigatus.
AB  - Intravenous infection of guinea pigs with the fungus Aspergillus fumigatus
      resulted in increased levels of chitinase in serum and tissues of the animals.
      The molecular properties of the enzyme were demonstrated to be different from
      those of the fungal chitinase, but also from guinea pig lysozyme and beta-N
      acetylhexosaminidase. Bio-Gel P-100 gel filtration showed that in liver, spleen,
      heart and lung tissue of control animals there were two molecular mass forms
      present with apparent molecular masses of 35 kDa and 15 kDa. In brain and serum,
      only the 35 kDa form was detectable. Kidney showed only the 15 kDa form. Upon
      infection the 35 kDa form appeared in kidney and increased in the other tissues.
      When a less pathogenic form of the fungus was used the 35 kDa form remained
      absent in kidney. In contrast to human serum chitinase, the enzyme from guinea
      pig serum and tissues did bind to concanavalin A-Sepharose. This was the case for
      both molecular mass forms. The mode of cleavage of the substrate 4
      methylumbelliferyl-tri-N-acetylchitotrioside (MU-[GlcNAc]3, where GlcNAc is N
      acetylglucosamine) by the two forms of the enzyme was the same: both [GlcNAc]2
      and [GlcNAc]3 were released. The chitinase activity levels in the control tissues
      showed a large variation in this order: spleen > lung, kidney > liver > heart >
      brain. The fact that spleen showed the highest chitinase level is in agreement
      with its major role as a lymphoid organ in cases of systemic infections. The
      relative increases upon infection were the highest for the tissues that showed
      low control values.

PMID- 10206705
TI  - KNR4, a suppressor of Saccharomyces cerevisiae cwh mutants, is involved in the
      transcriptional control of chitin synthase genes.
AB  - The KNR4 gene, originally isolated by complementation of a K9 killer-toxin
      resistant mutant displaying reduced levels of both 1,3-beta-glucan and 1,3-beta
      glucan synthase activity, was recloned from a YCp50 genomic library as a
      suppressor of Saccharomyces cerevisiae calcofluor-white-hypersensitive (cwh)
      mutants. In these mutants, which were characterized by increased chitin levels,
      the suppressor effect of KNR4 resulted, for some of them, in a lowering of
      polymer content to close to wild-type level, with no effect on the contents of
      beta-glucan and mannan. In all cases, this effect was accompanied by a strong
      reduction in mRNA levels corresponding to CHS1, CHS2 and CHS3, encoding chitin
      synthases, without affecting expression of FKS1 and RHO1, two genes encoding the
      catalytic subunit and a regulatory component of 1,3-beta-glucan synthase,
      respectively. Overexpression of KNR4 also inhibited expression of CHS genes in
      wild-type strains and in two other cwh mutants, whose sensitivity to calcofluor
      white was not suppressed by this gene. The physiological relevance of the KNR4
      transcriptional effect was addressed in two different ways. In a wild-type strain
      exposed to alpha-factor, overexpression of this gene inhibited CHS1 induction and
      delayed shmoo formation, two events which are triggered in response to the
      pheromone, whereas it did not affect bud formation and cell growth in a chs1 chs2
      double mutant. A chimeric protein made by fusing green fluorescent protein to the
      C terminus of Knr4p which fully complemented a knr4delta mutation was found to
      localize in patches at presumptive bud sites in unbudded cells and at the
      incipient bud site during bud emergence. Taken together, these results
      demonstrate that KNR4 has a regulatory role in chitin deposition and in cell wall
      assembly. A mechanism by which this gene affects expression of CHS genes is
      proposed.

PMID- 10206707
TI  - Oxidation of medium-chain acyl-CoA esters by extracts of Aspergillus niger:
      enzymology and characterization of intermediates by HPLC.
AB  - The activities of beta-oxidation enzymes were measured in extracts of glucose-
      and triolein-grown cells of Aspergillus niger. Growth on triolein stimulated
      increased enzyme activity, especially for acyl-CoA dehydrogenase. No acyl-CoA
      oxidase activity was detected. HPLC analysis after incubation of triolein-grown
      cell extracts with decanoyl-CoA showed that beta-oxidation was limited to one
      cycle. Octanoyl-CoA accumulated as the decanoyl-CoA was oxidized. Beta-oxidation
      enzymes in isolated mitochondrial fractions were also studied. The results are
      discussed in the context of methyl ketone production by fungi.

PMID- 10206710
TI  - Reasons why 'Leptospirillum'-like species rather than Thiobacillus ferrooxidans
      are the dominant iron-oxidizing bacteria in many commercial processes for the
      biooxidation of pyrite and related ores.

PMID- 10206708
TI  - The TATA-box binding protein of Entamoeba histolytica: cloning of the gene and
      location of the protein by immunofluorescence and confocal microscopy.
AB  - A 309 bp DNA fragment from Entamoeba histolytica was amplified by PCR using
      primers derived from the Acanthamoeba castellanii consensus TATA-box binding
      protein amino acid sequence. The amplified fragment was used to isolate cDNA and
      genomic DNA clones containing an ORF encoding the complete E. histolytica TATA
      box binding protein (Ehtbp, 702 bp, 234 aa, molecular mass 26 kDa). The EhTBP
      functional domain showed 55% sequence identity to that of Homo sapiens, 54% to A.
      castellanii and 37% to Plasmodium falciparum TBPs. In Southern blot experiments
      we detected a single Ehtbp band, which was transcribed as a 1.3 kb mRNA
      containing a 420 nt 5' untranslated region. However, the probe hybridized with
      the 0.8 and 1.5 Mb chromosomes, suggesting that this sequence is diploid. In situ
      PCR assays showed two signals in 95% of trophozoites, one located in the nucleus
      and another in EhkO, the novel DNA-containing organelle recently reported. The
      recombinant E. histolytica TATA-box binding protein was expressed in Escherichia
      coli. Antibodies against it recognized two proteins of 26 and 29 kDa in E.
      histolytica nuclear extracts. Confocal microscopy immunofluorescence analysis
      located the protein in both the nucleus and EhkO.

PMID- 10206711
TI  - Bacillus subtilis 168 gene lytF encodes a gamma-D-glutamate-meso-diaminopimelate
      muropeptidase expressed by the alternative vegetative sigma factor, sigmaD.
AB  - A gamma-D-glutamate-meso-diaminopimelate muropeptidase was detected in the
      vegetative growth phase of Bacillus subtilis 168. It is encoded by the
      monocistronic lytF operon expressed by the alternative vegetative sigma factor,
      sigmaD. Sequence analysis of LytF revealed two domains, an organization common to
      exoproteins of B. subtilis as well as to those from other organisms. The N
      terminal domain contains a fivefold-repeated motif attributed to cell wall
      binding, whilst the C-terminal domain is probably endowed with the catalytic
      activity. Overexpression of LytF allowed its purification and biochemical
      characterization. Inactivation of lytF led to the loss of the cell-wall-bound
      protein 49' (CWBP49') and of the corresponding lytic activity as revealed by
      renaturation gel assay. Native cell walls prepared from the multiple lytC lytD
      lytE lytF-deficient mutant did not exhibit any autolysis, whereas walls prepared
      from a strain endowed with LytF but not with the other three enzymes underwent a
      slight lysis. Analysis of degradation products of cell wall devoid of teichoic
      acid-bound O-esterified D-alanine unambiguously confirmed that LytF cuts the
      gamma-D-glutamate-mesodiaminopimelate bond.

PMID- 10206709
TI  - Transcriptional regulation of molybdoenzyme synthesis in Escherichia coli in
      response to molybdenum: ModE-molybdate, a repressor of the modABCD (molybdate
      transport) operon is a secondary transcriptional activator for the hyc and nar
      operons.
AB  - Escherichia coli growing under anaerobic conditions produces several
      molybdoenzymes, such as formate hydrogenlyase (formate to H2 and CO2; hyc and
      fdhF genes) and nitrate reductase (narGHJI genes). Synthesis of these
      molybdoenzymes, even in the presence of the cognate transcriptional activators
      and effectors, requires molybdate in the medium. Besides the need for
      molybdopterin cofactor synthesis, molybdate is also required for transcription of
      the genes encoding these molybdoenzymes. In E. coli, ModE was previously
      identified as a repressor controlling transcription of the operon encoding
      molybdate transport components (modABCD). In this work, the ModE protein was also
      found to be a required component in the activation of hyc-lacZ to an optimum
      level, but only in the presence of molybdate. Mutant ModE proteins which are
      molybdate-independent for repression of modA-lacZ also restored hyc-lacZ
      expression to the wild-type level even in the absence of molybdate. Nitrate
      dependent enhancement of transcription of narX-lacZ was completely abolished in a
      modE mutant. Nitrate-response by narG-lacZ and narK-lacZ was reduced by about 50%
      in a modE mutant. DNase I footprinting experiments revealed that the ModE protein
      binds the hyc promoter DNA in the presence of molybdate. ModE-molybdate also
      protected DNA in the intergenic region between narXL and narK from DNase I
      hydrolysis. DNA sequences (5' TAYAT 3' and 5' GTTA 3') found in ModE-molybdate
      protected modABCD operator DNA were also found in the ModE-molybdate-protected
      region of hyc promoter DNA (5' GTTA-7 bp-CATAT 3') and narX-narK intergenic
      region (5' GTTA-7 bp-TACAT 3'). Based on these results, a working model is
      proposed in which ModE-molybdate serves as a secondary transcriptional activator
      of both the hyc and narXL operons which are activated primarily by the
      transcriptional activators, FhlA and NarL, respectively.

PMID- 10206712
TI  - The ribR gene encodes a monofunctional riboflavin kinase which is involved in
      regulation of the Bacillus subtilis riboflavin operon.
AB  - A 3.5 kb EcoRI-BamHI fragment of Bacillus subtilis chromosomal DNA carrying the
      ribR gene, involved in regulation of the B. subtilis riboflavin operon, was
      cloned in the B. subtilis-Escherichia coli shuttle vector pCB20. DNA sequence
      analysis of this fragment revealed several ORFs, one of which encodes a
      polypeptide of 230 amino acids with up to 45% sequence identity with FAD
      synthetases from a number of micro-organisms, such as Corynebacterium
      ammoniagenes, E. coli and Pseudomonas fluorescens, and also to the ribC gene
      product of B. subtilis. The ribR gene was amplified by PCR, cloned and expressed
      in E. coli. Measurement of flavokinase activity in cell extracts demonstrated
      that ribR encodes a monofunctional flavokinase which converts riboflavin into FMN
      but not to FAD, and is specific for the reduced form of riboflavin.

PMID- 10206713
TI  - Functional analysis of upstream regulating regions from the Yarrowia lipolytica
      XPR2 promoter.
AB  - The XPR2 gene from Yarrowia lipolytica encodes an inducible alkaline
      extracellular protease. Its complex regulation involves pH, carbon, nitrogen and
      peptones. Two previously identified upstream activating sequence (UAS) regions
      were analysed in a reporter system, outside the XPR2 context. Fragments from the
      UAS regions were inserted upstream of a minimal LEU2 promoter directing the
      expression of a reporter gene. The activity of the hybrid promoters was assessed
      following integration into the Y. lipolytica genome. This study confirmed the
      presence of two UASs composed of several interacting elements. Within the distal
      UAS (UAS1), a TUF/RAP1 binding site exhibited a UAS activity, which was enhanced
      by the presence of two adjacent repeats, overlapping sites similar to the CAR1
      upstream repressing sequence from Saccharomyces cerevisiae. Within the proximal
      UAS (UAS2), the UAS activity required the interaction of both an ABF1-like
      binding site and a decameric repeat, containing Aspergillus nidulans PacC site
      consensus sequences. This decameric repeat was able to mediate repression due to
      carbon and/or nitrogen sources as well as pH-dependent activation. A study in the
      context of trans-regulatory mutations in the Y. lipolytica RIM101 gene showed
      that the PacC-like sites, potential binding sites for YlRim101p, were implicated
      in the derepression of UAS2-driven expression at neutral-alkaline pH. The in vivo
      response of the PacC-like decamers to external pH was dependent on the status of
      the pH-regulated activator YlRim101p, which is homologous to the A. nidulans PacC
      regulator. The carbon/nitrogen regulation imposed on the decamers was shown to be
      independent of YlRim101p and to override its effects.

PMID- 10206714
TI  - Cloning, sequencing and molecular analysis of the Campylobacter jejuni groESL
      bicistronic operon.
AB  - The groESL bicistronic operon from the enteric pathogen Campylobacter jejuni was
      cloned and sequenced. It consists of two ORFs encoding proteins with molecular
      masses of 9.5 and 57.9 kDa, which showed a high degree of homology to other
      bacterial GroES and GroEL proteins. Northern blot analysis suggested that the
      groESL operon is transcribed as a bicistronic mRNA, and its steady-state level
      was markedly increased after temperature upshift. By primer extension assay, one
      potential transcription start point preceding the groESL genes could be
      demonstrated, and a putative promoter region compatible with both Escherichia
      coli and C. jejuni sigma70 consensus sequences was identified. A conserved
      inverted repeat, which is believed to be involved in the regulation of the groESL
      genes, was found between the -10 promoter box and the groES translation start
      site. The complete coding region of groEL was fused with pET-22b(+) and expressed
      in E. coli as a His6-tagged recombinant protein (rCjHsp60-His). After
      purification, the protein was recognized by an anti-HSP60 monoclonal antibody.
      ELISA and Western immunoblotting experiments showed that IgG and IgA antibody
      responses against rCjHsp60-His were not significantly increased in sera from 24
      patients with sporadic Campylobacter infection when compared to sera from 16
      healthy controls.

PMID- 10206716
TI  - Mast cells and their mediators in cutaneous wound healing--active participants or
      innocent bystanders?
AB  - Mast cells are traditionally viewed as effector cells of immediate type
      hypersensitivity reactions. There is, however, a growing body of evidence that
      the cells might play an important role in the maintenance of tissue homeostasis
      and repair. We here present our own data and those from the literature
      elucidating the possible role of mast cells during wound healing. Studies on the
      fate of mast cells in scars of varying ages suggest that these cells degranulate
      during wounding, with a marked decrease of chymase-positive cells, although the
      total number of cells does not decrease, based on SCF-receptor staining. Mast
      cells contain a plethora of preformed mediators like heparin, histamine,
      tryptase, chymase, VEGF and TNF-alpha which, on release during the initial stages
      of wound healing, affect bleeding and subsequent coagulation and acute
      inflammation. Various additional vasoactive and chemotactic, rapidly generated
      mediators (C3a, C5a, LTB4, LTC4, PAF) will contribute to these processes, whereas
      mast cell-derived proinflammatory and growth promoting peptide mediators (VEGF,
      FGF-2, PDGF, TGF-beta, NGF, IL-4, IL-8) contribute to neoangiogenesis,
      fibrinogenesis or re-epithelization during the repair process. The increasing
      number of tryptase-positive mast cells in older scars suggest that these cells
      continue to be exposed to specific chemotactic, growth- and differentiation
      promoting factors throughout the process of tissue remodelling. All these data
      indicate that mast cells contribute in a major way to wound healing. their role
      as potential initiators of or as contributors to this process, compared to other
      cell types, will however have to be further elucidated.

PMID- 10206715
TI  - Differentiation of Campylobacter coli and C. jejuni by length and DNA sequence of
      the 16S-23S rRNA internal spacer region.
AB  - The internal spacer region (ISR) between the 16S and 23S rRNA genes of
      Campylobacter was investigated by PCR fragment length typing and DNA sequencing
      of clinical and chicken wild-type isolates. PCR fragment length typing showed one
      fragment of 859 nt in length for the 12 strains of Campylobacter coli
      investigated. Thirty-six of the Campylobacter jejuni subsp. jejuni strains
      possessed one fragment, which varied in size between 727 and 802 nt. Three
      strains showed two fragments between 501 and 923 nt. Strains of C. jejuni subsp.
      doylei, Campylobacter lari and Campylobacter upsaliensis possessed one or two
      fragments with lengths different from those of C. coli and C. jejuni subsp.
      jejuni. DNA sequences were obtained from 54 nt downstream of rrs up to rrl of
      four strains of C. coli, eight strains of C. jejuni subsp. jejuni, and one strain
      each of C. jejuni subsp. doylei and C. lari, selected to represent the different
      biotypes of Campylobacter. ISR lengths determined by PCR fragment length typing
      and DNA sequencing corresponded for 12 strains. For two strains of C. coli, PCR
      fragment length typing underestimated ISR lengths by 159 and 193 nt, probably
      related to incomplete resolution of the distal helical structures, which were not
      fully denatured during PAGE. For the 14 strains and the published C. jejuni
      subsp. jejuni sequence, the first 206-211 nt were conserved and included the two
      tRNA genes in the characteristic tRNA(Ala) to tRNA(Ile) order separated by a
      short 8-9 nt spacer region. Within the region downstream of tRNA(Ile) conserved
      regions were identified which allowed a separation of C. lari from C. coli and C.
      jejuni but not separation of C. coli from C. jejuni. The 69-282 nt longer
      variable regions in C. coli strains allowed separation of this species from C.
      jejuni, confirming results obtained by PCR typing. Certain nucleic acid positions
      in variable regions were related to the Lior biotypes. Sequence information from
      ISRs of more strains is needed to ascertain if separation of species and biotypes
      will be possible for diagnostic purposes.

PMID- 10206717
TI  - Effect of type XII or XIV collagen NC-3 domain on the human dermal fibroblast
      migration into reconstituted collagen gel.
AB  - Type XII and XIV collagens localize near the surface of banded collagen fibrils
      and most likely work as a molecular bridge between collagen fibrils. We have
      shown that both collagens can modulate the interactions between collagen fibrils,
      allowing fibroblasts to act upon the fibrils to vary the deformability. In the
      present study the effect of the globular domains (collagenase-resistant domains)
      of type XII and XIV collagens (XII-NC-3 and XIV-NC-3) on the migration of
      fibroblasts into the reconstituted type I collagen gel was investigated. Cell
      attachment and proliferation on the collagen gel were unaffected. The migration
      of fibroblasts into the gel was increased proportionally to the concentration of
      collagen. We found that XII-NC-3 and XIV-NC-3 domains caused decreases in the
      numbers of fibroblasts that migrated into the gel. Heat treatment of XII-NC-3 and
      XIV-NC-3 or the addition of polyclonal antibodies eliminated the suppressive
      activity on fibroblast migration, showing that the intact conformation of NC-3
      domain is important for suppression of migration. The results suggest that both
      NC-3 domains influence the deformability of type I collagen fibril networks,
      which may cause the change in fibroblast migration.

PMID- 10206718
TI  - A recurrent frameshift mutation in exon 19 of the type VII collagen gene (COL7A1)
      in Mexican patients with recessive dystrophic epidermolysis bullosa.
AB  - Dystrophic epidermolysis bullosa (DEB) is an inherited blistering skin disorder
      caused by mutations in the type VII collagen gene (COL7A1). In this study, we
      determined the molecular basis of autosomal recessive DEB in a 19-year-old
      Hispanic Mexican woman by PCR amplification of genomic DNA, heteroduplex
      analysis, and automated sequencing of heteroduplex bandshifts. This approach
      revealed a homozygous frameshift mutation, 2470insG, in exon 19 of COL7A1 and
      resulted in attenuated basement membrane zone expression of type VII collagen, a
      reduced number of anchoring fibrils at the dermal-epidermal junction, and a sub
      lamina densa level of blister formation. Clinically, the patient had widespread
      trauma-induced skin fragility and complete loss of the nails, but had less
      pseudosyndactyly of the fingers and toes and milder mucosal involvement compared
      to most patients with the generalized form of this genodermatosis. We also
      screened 7 other Hispanic-Mexican patients with recessive DEB, none of whom were
      known to be related to this individual, for the mutation 2470insG using
      heteroduplex analysis and direct sequencing and detected this mutation on 7/14
      alleles. Haplotype analysis using intragenic COL7A1 and flanking polymorphisms
      and microsatellite markers revealed that all the mutant alleles had arisen on
      similar allelic backgrounds, consistent with propagation of a common Hispanic
      Mexican ancestral haplotype. In view of the high allelic frequency of the
      mutation 2470insG in the patients studied, we recommend initial screening for
      this mutation when attempting to identify the molecular pathology of recessive
      DEB in Hispanic Mexican patients.

PMID- 10206719
TI  - Enzymatic dissociation of keratinocytes from human skin biopsies for in vitro
      cell propagation.
AB  - Four techniques for dissociation of skin biopsies were compared to identify the
      method of choice for optimal expansion of isolated keratinocytes. Equivalent
      biopsies were obtained from 4 healthy human subjects and each divided into four
      parts. One part was minced and placed in a trypsinizing flask containing 0.05%
      trypsin and 0.01% ethylenediaminetetraacetic acid (EDTA). Released cells were
      harvested hourly. With the other parts, the epidermis was separated from the
      dermis after treatment with 0.5 mg/nml thermolysin, 2.5 mg/ml Dispase, or 0.17%
      trypsin and the epidermal portions were minced and incubated for 1 h in
      trypsin:EDTA. The cells were cocultivated with irradiated 3T3 fibroblasts to
      study the keratinocytes proliferative capacity. Freshly isolated cells were
      immunostained with anti-vimentin antibodies or grown in fibroblast-supportive
      conditions to detect the presence of human dermal fibroblasts. The mean number of
      cells dissociated per cm2 biopsy was higher after trypsin:EDTA digestion of a
      dermis-containing biopsy using a trypsinizing flask (4.0x 10(6) cells/cm2)
      compared to a biopsy where dermis-epidermis had been separated by thermolysin
      (2.8x 10(6) cells/cm2), Dispase (2.3x 10(6) cells/cm2) or trypsin (1.1 x 10(6)
      cells/cm2). Between 0.5% and 4% of the cells dissociated from a dermis-containing
      biopsy were human fibroblasts. This comprised more than twice the number of
      fibroblasts obtained by using epidermal/dermal split techniques. The
      proliferative capacity in primary and secondary culture was higher in cells
      isolated by trypsin:EDTA incubation in the trypsinizing flask or after epidermal
      dermal separation using thermolysin, suggesting that Dispase or trypsin may have
      a more detrimental effect on the isolated keratinocytes. Our results show that
      dissociating the cells by trypsin:EDTA incubation in a trypsinizing flask or
      after epidermal-dermal separation using thermolysin, are preferable methods for
      isolating keratinocytes from human skin.

PMID- 10206720
TI  - Administration of acetylcholine and vasoactive intestinal polypeptide to atopic
      eczema patients.
AB  - Responses to acetylcholine (ACh) and vasoactive intestinal polypeptide (VIP) were
      investigated in atopic eczema (AE) patients. To elucidate the involvement of
      histamine to ACh-provoked vasoreactions and sensations, we applied a selective H1
      antagonist (cetirizine) 3 h prior to the ACh-administration. Solutions of
      acetylcholine (ACh, 0.55 M) and vasoactive intestinal polypeptide (VIP, 1.5x 10(
      5) M) were injected (10 microl) intracutaneously into the volar forearm of 14
      healthy subjects and 14 atopic eczema (AE) patients. The substances were applied
      as single stimulus as well as in combination. Sensations evoked by the
      stimulation were recorded using 2 visual analog scales (VAS). Vasoreactions were
      analyzed with the new technique of computer assisted video image analysis. With
      this method we measured the dynamics of the flare development and the extension
      of the final flare size independent of the observer's assessment. In control
      subjects the development and extension of the final flare size was almost
      similar, regardless whether ACh and VIP were applied in combination or
      separately. Compared to healthy controls, after injection of ACh, VIP and the
      combination of VIP and ACh smaller flare sizes were recorded in AE patients.
      After VIP was given, the control subjects reported pruritus, which was
      significantly augmented compared to AE patients. In contrast, controls reported a
      burning pain after the injection of ACh, whereas AE patients felt predominantly
      pruritus. Itch sensation after the combined application of VIP and ACh was
      significantly elevated in AE patients. Consequently, we assume that mediators of
      sudomotor neurons, i.e., VIP and ACh meet in AE patients apparently sensitized
      nociceptive primary afferents and induce exaggerated itch, pain and flare
      responses. When pretreated with the selective H1-antagonist cetirizine before ACh
      was injected, pain and erythema due to ACh was diminished in healthy controls. In
      contrast, cetirizine did not influence the size of erythema and the magnitude of
      sensation in AE patients. We conclude, that the release of histamine is not
      involved in ACh-induced erythema and pruritus in AE. These data provide evidence
      that pruritus can be elicited in atopic eczema by a cholinergic, histamine
      independent mechanism.

PMID- 10206721
TI  - Structural changes of human epidermis induced by human leukocyte-derived
      proteases.
AB  - During the process of inflammation human neutrophils release potent serine
      proteases, such as human leukocyte elastase and cathepsin G. In psoriasis these
      enzymes are released within the epidermis. To investigate the destructive
      potential of neutrophil-derived serine proteases these were applied on viable
      human epidermis as well as full thickness human skin in vitro. Human leukocyte
      elastase and cathepsin G were found to dissociate keratinocytes from epidermal
      sheets in a time- and dose-dependent fashion. Significant keratinocyte
      dissociation was observed 4 h after application of 3 nM human leukocyte elastase.
      By electron microscopy of elastase- or cathepsin G-treated full thickness human
      skin, widening of the extracellular space followed by complete separation of
      keratinocytes without intradesmosomal cleavage was observed. In addition,
      cathepsin G induced membrane damage as well as destruction of intracellular
      organelles. Thus, neutrophil-derived serine proteases exert pronounced
      destructive potential in human epidermis in concentrations likely to appear in
      lesional psoriatic skin.

PMID- 10206722
TI  - Analysis of cultured keratinocytes from a transgenic mouse model of psoriasis:
      effects of suprabasal integrin expression on keratinocyte adhesion, proliferation
      and terminal differentiation.
AB  - Many important transgenic mouse models of benign and neoplastic skin diseases
      have been generated through the use of promoters that target transgene expression
      to the different epidermal layers. However, more mechanistic studies of the
      specific effects of the transgenes on keratinocytes have been hampered by
      difficulties in culturing keratinocytes from adult mouse epidermis and by the low
      differentiation potential of many established mouse keratinocyte lines. We have
      used the Rheinwald & Green technique to cultivate primary adult keratinocytes and
      to generate keratinocyte lines from transgenic mice which have a sporadic
      psoriatic phenotype due to expression of human integrin subunits under the
      control of the involucrin promoter. We show that the transgenes are induced when
      keratinocytes are placed in suspension and that the transgenic integrins are
      capable of clustering in focal adhesions and mediating cell adhesion and
      spreading. We also show that suprabasal integrin expression has no direct effect
      on proliferation of cells in the underlying basal layer, ruling this out as a
      possible explanation for the epidermal hyperproliferation observed in the
      transgenic mice.

PMID- 10206723
TI  - Human herpesvirus 8 (HHV-8) in familial Kaposi's sarcoma.
AB  - Human herpesvirus 8 (HHV-8) has been detected in various epidemiological forms of
      Kaposi's sarcoma (KS). Since familial KS cases are exceedingly rare and the
      occurrence of familial KS in siblings has thought to depend rather on genetic
      factors than on a viral factor, familial KS has not been investigated for the
      presence of HHV-8. To investigate whether HHV-8 is present also in this rare form
      of KS, we examined tumor biopsies of 2 siblings with familial KS for the presence
      of HHV-8 specific DNA sequences by a nested PCR protocol. HHV-8 DNA sequences
      could be detected in KS specimens of both patients. Sequence analysis revealed an
      identical DNA sequence of HHV-8 in KS tissue of both siblings, but the sequence
      in our cases differs in one base pair at position 67 from the previously
      published HHV-8 KS330Bam fragment. The findings indicate that besides the yet
      poorly defined genetical factors involved in the pathogenesis of KS, HHV-8 may
      act as a cofactor also in familial KS. In addition, our data demonstrate that HHV
      8 is found in all epidemiological forms of KS, including the rarely occurring
      familial KS. Familial KS may act as a further model to study the interaction of
      an oncogenic virus with genetic host factors in the context of a neoplastic
      disorder.

PMID- 10206724
TI  - Evidence that apoptosis and terminal differentiation of epidermal keratinocytes
      are distinct processes.
AB  - Although there are clear parallels between apoptosis and epidermal terminal
      differentiation it is unclear whether terminal differentiation of keratinocytes
      is a form of apoptosis. We found that apoptosis was rare in adherent cultures of
      normal keratinocytes, even when growth factors were removed. When keratinocytes
      were placed in suspension for 24-96 h the majority of cells were induced to
      undergo terminal differentiation, as assessed by involucrin expression and
      cornified envelope assembly, but few cells underwent apoptosis, as assessed by
      morphological examination, TUNEL labelling and by DNA laddering. Withdrawal of
      serum and growth factors stimulated apoptosis of suspended keratinocytes but led
      to some reduction in the number of cells that underwent terminal differentiation.
      At 96 h the majority of cells retained their nuclei in the presence or absence of
      serum and growth factors. In normal epidermis only occasional cells within the
      granular layer had apoptotic nuclei, determined by TUNEL labelling and light and
      electron microscopy. In affected epidermis of psoriasis, Darier's disease and
      pityriasis rubra pilaris, diseases characterized by perturbation of growth,
      differentiation or adhesion, light microscopy revealed no higher proportion of
      apoptotic nuclei than in normal epidermis. However, the majority of viable
      epidermal layers in diseased skin were positive by TUNEL labelling, suggesting
      that TUNEL is not always a specific marker of apoptosis in keratinocytes. We
      conclude that in vivo and in culture keratinocyte terminal differentiation and
      apoptosis are distinct cellular events, subject to different stimuli.

PMID- 10206725
TI  - Epithelial stem cells in the skin: definition, markers, localization and
      functions.
AB  - In recent years, cutaneous epithelial stem cells have attained a genuine
      celebrity status. They are considered the key resource for epidermal and skin
      appendage regeneration, and are proposed as a preferential target of cutaneous
      gene therapy. Follicular epithelial stem cells may also give rise to a large
      variety of epithelial tumors, and cutaneous epithelial stem cells likely are
      crucial targets for physical or chemical agents (including carcinogens) that
      damage the skin and its appendages. However, as this Controversies feature
      illustrates, few experts can agree on how exactly to define and identify these
      elusive cells, or on where precisely in the skin they are localized. Given their
      potential importance in skin biology, pathology and future dermatological
      therapy, it is, therefore, timely to carefully reconsider the basic questions:
      What exactly is a stem cell, and how can we reliably identify epithelial stem
      cells? How many different kinds are there, and how do they differ functionally?
      Where exactly in the skin epithelium is each of the putative stem cell
      subpopulations located, and can we selectively manipulate any of them?

PMID- 10206726
TI  - Effects of moisture and sorption on bioavailability of p-hydroxybenzoic acid to
      Arthrobacter sp. in soil.
AB  - Effects of bioavailability on degradation of 14C-p-hydroxybenzoate were examined
      using sterile soil inoculated with Arthrobacter sp. Physical accessibility of p
      hydroxybenzoate was controlled by varying pore continuity with a range of
      moisture regimes (-33 to -420 kPa), whereas sorption was controlled via addition
      of an exchange resin. Arthrobacter sp. accessed 94% of p-hydroxybenzoate in soil
      at -33 kPa, owing to continuity of soil pores and sufficient cells to exploit
      available space. A deviation in degradation kinetics at -420 kPa soil was
      attributed to inaccessible p-hydroxybenzoate in solution. Addition of resin
      decreased extent of degradation, though the effect diminished as pore continuity
      decreased. Subtle differences in effects of these processes on degradation
      kinetics may facilitate their separate treatment in environmental fate models.

PMID- 10206728
TI  - [VIII Congress of the Catalan Society of Digestion. Palma de Mallorca, Spain, 29
      31 January 1999. Abstracts].

PMID- 10206729
TI  - Veterinary medicine in Canada: opportunity for renewal. A report by the CVMA Task
      Force on the future of the veterinary profession.

PMID- 10206730
TI  - Report of the Canadian Veterinary Medical Association Expert Panel on rBST.
      Executive Summary.

PMID- 10206731
TI  - Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
      Basic and clinical issues in multiple sclerosis research. 18 October 1998,
      Montreal, Quebec, Canada. Proceedings.

PMID- 10206732
TI  - Therapy for ulcers and erosions associated with nonsteroidal anti-inflammatory
      drugs.

PMID- 10206733
TI  - Structures of P-type transporting ATPases and chromosomal locations of their
      genes.
AB  - P-type ATPases (E1E2-ATPases) are primary active transporters which form phospho
      intermediates during their catalytic cycle. They are classified into P1 to P4
      based on the primary structure and potential transmembrane segments. Although the
      classic P-type ATPases are cation transporters, two new members have recently
      been found; one is a flippase catalyzing the flip-flop movement of
      aminophospholipids, but the substrate and function of the other one remain
      unknown. It would be interesting to determine whether the cations and
      aminophospholipids are transported by similar or different mechanisms. P-type
      ATPases are believed to have been derived from a common ancestor, and their genes
      are found to be distributed in various chromosomal loci. However, gene
      duplication events can be traced from the tandem arrangement of genes and their
      linkage map. Na+/K+- and H+/K+-ATPases have not only closely related a subunits
      but also similar beta subunits. Renal Na+/K+-ATPase has an additional subunit
      gamma. Similar small polypeptides (phospholemman, Mat-8 and CHIF), which induce
      Cl- and K+ currents, have been found. The idea of their functional and structural
      coupling with P-type ATPases, especially with H+/K+-ATPase, is intriguing. Each P
      type ATPase must have specific domains or sequences for its intracellular
      trafficking (sorting, retention and recycling). Identification of such regions
      and studies on the molecules playing role in their recognition may facilitate the
      unveiling of various cellular processes regulated by P-type ATPases.

PMID- 10206734
TI  - Bilirubin binding activity of cytokeratin 18 isolated from the porcine liver.
AB  - A porcine liver 40 kDa protein designated SBP40 isolated by affinity
      chromatography with agarose-linked spermine was identified as a porcine
      cytokeratin 18 on the basis of partial amino acid sequences of peptides derived
      by lysylendopeptidase digestion and by its reactivity with two commercially
      available preparations of monoclonal antibody. Immunohistochemistry revealed that
      SBP40 is localized at the hepatocyte membranes, preferentially in the bile
      canalicular area in accordance with the previously reported localization of
      cytokertain 18 in the murine liver. Affinity chromatography with agarose-linked
      bilirubin, a solubilization experiment of bilirubin from bilirubin-Sephadex G-10
      complex, and gel-filtration of a mixture with bilirubin demonstrated that SBP40
      or porcine cytokeratin 18 has binding affinity for bilirubin. These results
      suggest that cytokeratin 18 may play a role as a membrane reservoir in the event
      of transport and secretion of bile pigments in the liver.

PMID- 10206735
TI  - Lipid mobilization and acid phosphatase activity in lytic compartments during
      conidium dormancy and appressorium formation of Colletotrichum graminicola.
AB  - Colletotrichum graminicola, a pathogen of sorghum and corn, was investigated
      prior and during germination as to certain aspects of acid phosphatase activity
      and lipid mobilization. Ungerminated conidia cytoplasm was filled with lipid
      deposits, which were mobilized during the germination process. Cytochemical
      ultrastructural examination showed that conidia vacuoles exhibit acid phosphatase
      activity, which is suggestive of lytic activity. Lipid bodies, stored in the
      ungerminated conidia cytoplasm, were internalized by vacuoles in a process
      analogous to microautophagy and were apparently digested inside them. The lipid
      bodies disappeared and vacuoles became enlarged in conidial cells during
      germination. Appressoria also showed acid phosphatase activity in multiple
      heterogeneous vesicles which were, in most cases, juxtaposed with lipid bodies.
      These results suggest that the vacuolar system plays an important role during C.
      graminicola germination and that the initial stages of lipid metabolization are
      taking place inside the vacuoles.

PMID- 10206736
TI  - Analysis of the sinusoidal endothelial cell organization during the developmental
      stage of the fetal rat liver using a sinusoidal endothelial cell specific
      antibody, SE-1.
AB  - The sinusoid organization during the development of fetal rat livers was studied
      using a SE-1 antibody, which we have previously established as a specific
      monoclonal antibody against rat sinusoidal endothelial cell (SEC). Expression and
      localization of the SE-1 antigen in the liver tissues of 13- to 21-day-old
      fetuses were immunofluorescently and immunoelectron microscopically examined. The
      first positive fluorescence was observed in the immature liver of 15-day-old
      fetuses. The initial positive staining was randomly distributed in the liver
      parenchyma and showed no direct relation to the large vessels which may be
      derived from the fetal vitelline veins. The positive linear staining increased in
      number and connected with each other during the course of development. The SE-1
      staining pattern and the sinusoidal arrangement became similar to those of the
      adult liver after 20th day of gestation. Immunoelectron microscopically, the
      immature SEC showed a weak positive reaction for the SE-1 antigen at their
      membrane and was observed together with immature hepatocytes and hematopoietic
      cells in the 15-day-old fetal liver. Along with the liver development, SEC formed
      a sinusoid structure closely associated with hepatocytes and came to strongly
      express the SE-1 antigen. These results indicate that the organization of the
      hepatic sinusoid may start at around 15th day of the gestation and occurs
      randomly in the fetal liver parenchyma. It is also suggested that the expression
      of SE-1 antigen is possibly regulated by the intimate association with
      hepatocytes.

PMID- 10206737
TI  - Antibodies with the cell-type specificity to the morula cells of the solitary
      ascidians Styela rustica and Boltenia echinata.
AB  - The separation of the blood cells of Styela rustica (Styelidae, Stolidobranchiae)
      in discontinuous Percoll gradient showed 4 fractions. The 4th and bottom most
      fraction contained 90-100% of morula cells. The protein composition of the morula
      cell fraction revealed on SDS-PAGE showed two major proteins with m.w. 47 and 26
      kDa. These proteins were heavily positively charged. Polyclonal antiserums
      against these proteins were raised. Each antiserum reacted with both proteins
      only in morula cells on the blot after SDS-PAGE and stained the proper protein
      without crossreaction on the blot after AU-PAGE. The only type of cells stained
      with antibodies in circulating blood, in the tunic and on the tunic wound surface
      in paraffin sections of another species Boltenia echinata (Pyuridae,
      Stolidobranchiae) were morula cells. The morula-type specific antibodies obtained
      recognized major positively charged proteins which were apparently structural
      substrates for the phenoloxidase tanning.

PMID- 10206738
TI  - Cyclic AMP delays G2 progression and prevents efficient accumulation of cyclin B1
      proteins in mouse macrophage cells.
AB  - In mouse macrophage cells, the increase of the intracellular cAMP level activates
      protein kinase A (PKA) and results in inhibition of cell cycle progression in
      both G1 and G2/M phases. G1 arrest is mediated by a cdk inhibitor, p27Kip1, which
      prevents G1 cyclin/cdk complexes from being activated in response to colony
      stimulating factor-1, whereas inhibition of G2/M progression has not been fully
      elucidated. In this report we analyzed the effect of cAMP on G2/M progression in
      a mouse macrophage cell line, BAC1.2F5A. Flow cytometric analysis and mitotic
      index measurement using both synchronized and asynchronized cells revealed that
      addition of cAMP-elevating agents (8-bromoadenosine 3':5'-cyclic monophosphate
      and 3-isobutyl-methyl-xanthine), although they did not affect S phase progression
      or M/G1 transition, temporarily arrested cells in G2 but eventually the cells
      proceeded to M phase, resulting in about 4 hours delay of G2 progression. Timing
      of cyclin B1/Cdc2 kinase activation was also retarded by about 4 hours, which was
      accompanied by inhibition of efficient accumulation of cyclin B1 proteins.
      Initial induction and accumulation of cyclin B1 mRNA were not hampered, but the
      half life of cyclin B1 proteins was significantly shorter during G2 phase in the
      presence of cAMP-elevating agents compared with that of the cells blocked from
      progressing through M phase by nocodazole. These results imply that the cAMP/PKA
      pathway regulates G2 phase progression by altering the stability of a crucial
      cell cycle regulator.

PMID- 10206739
TI  - Phorbol 12-myristate 13-acetate induced cell death of porcine peripheral blood
      polymorphonuclear leucocytes.
AB  - Polymorphonuclear leucocytes (PMNs) circulating in mammalian peripheral blood are
      terminally differentiated cells, and once isolated in serum-free medium, they
      undergo apoptosis within 1 or 2 days. In this study, we studied the effects of
      phorbol myristate acetate (PMA) on the viability of porcine PMNs in vitro. PMA is
      known to suppress apoptosis in many cell types. PMA but not dioctanoyl glycerol
      (DOG) induced morphological degeneration and cell death within 3 to 5 hours as
      assessed by light microscopy observation and the MTT viability assay. This
      occurred despite the fact that DNA fragmentation associated with "spontaneous
      apoptosis" was not observed. Morphological degeneration and death were not due to
      the oxidative damage from superoxides or its metabolites produced by
      polymorphonuclear leucocytes, because PMA and DOG similarly stimulated superoxide
      production. Several other inactive phorbol derivatives tested did not cause cell
      death, suggesting that the toxicity of PMA did not result from non-specific
      effect of the reagent.

PMID- 10206740
TI  - Rough surfaced smooth endoplasmic reticulum in rat and mouse cerebellar Purkinje
      cells visualized by quick-freezing techniques.
AB  - The in vivo structure of the smooth endoplasmic reticulum (ER) was visualized in
      rat and mouse cerebellar Purkinje cells by using quick-freezing techniques
      followed by freeze-substitution for ultrathin-sectioning or freeze-fracturing and
      deep-etching for replicas. High magnification electron microscopy of the
      ultrathin sections revealed a surprising finding that all the smooth ER are
      apparently rough surfaced, and heavily studded with a large number of small dense
      projections. In the soma the smooth ER appears to be similar to its rough
      counterpart, except that the projections are slightly smaller, less electron
      dense and less protrusive on the ER membranes than the ribosomes. The projections
      were short rectangles, 20 x 20 x 6 nm3 in size, covering the cytoplasmic surface
      of the smooth ER in a checker-board manner where closely packed. After freeze
      etching and replication, they appeared to be composed of four subparticles,
      surrounding a central channel. Thus the projections are very similar to the foot
      structure (ryanodine receptor) of the sarcoplasmic reticulum. Furthermore, they
      were distributed exclusively in the ER compartment and were highly concentrated
      especially in the smooth ER. This localization of the projections coindides with
      the intracellular distribution of the inositol 1,4,5-trisphosphate (IP3) receptor
      determined by quantitative immunogold electron microscopy. These findings would
      suggest that the projections are tetramers of IP3 receptor molecules and could be
      used as a morphological marker for the smooth ER in Purkinje cells, which spreads
      from the soma to the axon and dendrite, up to the tips including the spines. In
      Purkinje cells tubular smooth ER runs freely in a serpentine fashion or are
      intertwined to make large membraneous tangles without forming cisternal stacks.
      It is highly probable that the ER cisternal stacks do not exist naturally in
      Purkinje cells but are formed artificially during the various procedures for
      chemical fixation.

PMID- 10206741
TI  - Phenylarsine oxide and ethanol prevent cell death of porcine polymorphonuclear
      leucocytes induced by phorbol myristate acetate.
AB  - In this study, we report that phenylarsine oxide and ethanol, both of which
      suppress a number of polymorphonuclear leucocyte functions including superoxide
      production, prevented the phorbol myristate acetate-induced cell death in a dose
      dependent manner. These reagents had an inhibitory effect even after
      polymorphonuclear leucocytes were stimulated to produce superoxide by treatment
      with phorbol myristate acetate. The results indicate that activation of protein
      kinase C and subsequent superoxide release do not directly cause phorbol
      myristate acetate-induced cell death. Phenylarsine oxide or ethanol prevents cell
      death by affecting pathways downstream from those involved in the superoxide
      production.

PMID- 10206742
TI  - Show me the proof, Dr. Avery.

PMID- 10206743
TI  - Alberta physician made a career of roughing it in the bush.

PMID- 10206745
TI  - Molecular typing of Malassezia species with PFGE and RAPD.
AB  - The currently recognized seven species of Malassezia all have different
      karyotypes which do not vary intraspecifically, except in M. furfur which
      displayed two different karyotypes. In contrast, random amplified polymorphic DNA
      (RAPD) typing showed the presence of genetic variation in all species. It is
      concluded that karyotype analysis is useful for species identification, and RAPD
      typing can be used in epidemiological investigations.

PMID- 10206744
TI  - Serodiagnosis of histoplasmosis, paracoccidioidomycosis and penicilliosis
      marneffei; current status and future trends.
AB  - Effective serodiagnosis of systemic fungal infections is of increasing
      importance, particularly with regard to the identification of infection with
      Histoplasma capsulatum, Paracoccidioides brasiliensis and Penicillium marneffei.
      Methodology has been based either around antibody or antigen detection, although
      there is clear overlap between the two. Antibody-based detection systems for the
      diagnosis of histoplasmosis, paracoccidioidomycosis and penicilliosis marneffei
      have now begun to incorporate a range of highly purified and well-characterized
      antigens, in contrast to the situation of a few years ago when relatively crude
      preparations derived from either whole cells or culture filtrate were used. The
      application of such antigens offers improvements in reproducibility and
      specificity, although the detection of meaningful antibody responses in
      immunosuppressed individuals remains a problem. Partly as a consequence of this a
      great deal of attention has focused on the development of antigen detection
      assays, and such methods have proved particularly successful, as for instance in
      the serodiagnosis of histoplasmosis in AIDS patients. The recent utilization of
      monoclonal antibodies in the development of antigen detection methods for the
      diagnosis of histoplasmosis and paracoccidioidomycosis offers further scope for
      improvement in this area.

PMID- 10206746
TI  - The relationship between the cell length, adhesion to acrylic and relative cell
      surface hydrophobicity of Candida parapsilosis.
AB  - Candida parapsilosis is an emerging opportunistic pathogen which causes systemic
      and superficial infections in immunocompromised hosts. Successful colonization
      and subsequent infection of the host by a microorganism depends upon its ability
      to adhere to host surfaces, and its relative cell surface hydrophobicity (CSH) is
      a contributory physical force involved in the process. During a comprehensive
      study of a battery of C. parapsilosis isolates, we noted wide variations in their
      cell size. Hence we examined the relationship between the cell length, in vitro
      adhesion to acrylic surfaces and relative CSH of 24 isolates of C. parapsilosis
      from superficial and systemic sources. A strong positive correlation was observed
      between the cell length and adhesion of Candida to acrylic surfaces (r=0.56;
      P=0.004) as well as the cell length and the relative CSH, as measured by a
      hydrocarbon assay method (r=0.72, P=0.0001). Further, the cell length of both the
      superficial and systemic isolates correlated well with their CSH (r=0.63, P=0.01;
      r=0.63, P=0.03 for superficial and systemic isolates, respectively). These data
      provide a tantalizing glimpse of the structural and functional dynamics of the
      candidal cell surface.

PMID- 10206748
TI  - Emmonsiosis of rodents in an agroecosystem.
AB  - Adiaspores of Emmonsia crescens were found in the lungs of 62.1% of 87 adult
      rodents from 10 windbreaks compared to only 8.2% of 184 adult rodents caught in
      10 adjacent arable fields in South Moravia, Czechland. A significantly higher
      mean weight proportion of plant remnants (predominantly small roots) was present
      in the soil from windbreaks (0.74%) than from fields (0.24%). In addition, mean
      relative abundance of rodents was significantly higher in windbreaks than in
      fields, and the windbreak soil was more acidic (pH 6.2 vs. 6.9, respectively). On
      the other hand, there was no significant difference in the water content (17.4%
      vs. 18.5%, respectively). The difference in the infection rate between the two
      habitats of the agroecosystem could be caused or affected by land use and farming
      technology.

PMID- 10206747
TI  - Morphological study of Trichophyton rubrum: ultrastructural findings after
      treatment with 4-amino-3-methyl-1-phenylpyrazolo-(3,4-c)isothiazole.
AB  - The antifungal activity of 4-amino-3-methyl-1-phenylpyrazolo-(3,4-c)isothiazole
      was studied on Trichophyton rubrum. The compound, at concentrations between 20
      and 10 microg ml(-1), induces a remarkable reduction in the growth and causes
      deep morphogenetic anomalies. The ultrastructural modifications have demonstrated
      that the compound targets the cell membrane of the fungus, breaking down not only
      the endomembrane system, but also the 'outer' membrane, with consequent extrusion
      of materials in the medium. The results suggests a mechanism of action similar to
      other azoles clinically utilized.

PMID- 10206749
TI  - Isolation of Cryptococcus neoformans var. neoformans from pigeon droppings
      collected throughout Turkey.
AB  - The six hundred and thirty-four samples of pigeon droppings were collected
      throughout Turkey, from 54 of 80 provinces. Cryptococcus neoformans was isolated
      from 29 (4.6%, overall) of 634 samples and 29 isolates were from 18 provinces.
      Interestingly, 16 (88.9%) of these provinces occur on the three different
      coastlines of Turkey, therefore the ecological role of a humid climate was
      speculated. Almost all isolates [28/29] were recovered from samples collected
      from roofs (n=14) and dovecotes (n=14). All isolates were found to be C.
      neoformans var. neoformans.

PMID- 10206750
TI  - Purification and characterization of a 315 kDa keratinolytic subtilisin-like
      serine protease from Microsporum canis and evidence of its secretion in naturally
      infected cats.
AB  - A keratinolytic protease, secreted as the major component by a feline clinical
      isolate of Microsporum canis cultivated in a minimal medium containing cat
      keratin, was purified by affinity chromatography on bacitracin agarose and gel
      filtration. The apparent molecular mass of the enzyme was 31.5 kDa and the pI was
      11.8. The enzyme was not glycosylated and its first 15 N-terminal amino acids
      showed numerous similarities with other fungal subtilisins. The optimum pH was
      around 9 while inactivation of the enzyme was reversible at pH 4, but not at pH
      11. The enzyme was stable at 37 degrees C with an apparent optimum temperature
      around 55 degrees C. PMSF, soybean trypsin inhibitor (SBTI) and chymostatin
      strongly inhibited the proteinase. The highest affinity (Km of 0.37 mM) and
      physiological efficiency (k(cat)/Km) were obtained for the synthetic substrate N
      Suc-Ala-Ala-Pro-Phe-p-nitroanilide. These results indicate that the keratinase
      belongs to the subtilisin-like serine protease family. Purified rabbit
      immunoglobulins G prepared against the keratinase and used in an
      immunohistochemical test allowed the detection of the keratinase produced by the
      fungus invading hair structures in naturally infected cats. The in vitro
      keratinolytic activity of the enzyme and its production in vivo suggest that it
      may contribute to pathogenicity.

PMID- 10206751
TI  - Involvement of the major glycoprotein (gp43) of Paracoccidioides brasiliensis in
      attachment to macrophages.
AB  - The yeast form of Paracoccidioides brasiliensis, the causative agent of a deep
      mycosis in humans, is known to be phagocytized by, and to multiply inside,
      macrophages. In this work we describe the involvement of gp43, a major antigenic
      protein of P. brasiliensis, in the initial steps of attachment of the fungus to
      macrophages. Anti-gp43 F(ab) polyclonal fragments were capable of inhibiting
      phagocytosis in a concentration-dependent manner. Sheep red blood cells
      sensitized with purified gp43 were more endocytized than SRBC alone, and this
      process was also inhibited by anti-gp43 F(ab) fragments. Inhibition tests
      indicated the involvement of fucose and mannose residues in the phagocytosis of
      the fungus and of SRBC-gp43 by macrophages. Taken together, these results suggest
      that gp43 may be involved in the adherence and uptake of the fungus by murine
      peritoneal macrophages, and that this binding may be dependent on monosaccharide
      residues that are part of the gp43 glycoprotein.

PMID- 10206752
TI  - Antigenic relationship between Loboa loboi and Paracoccidioides brasiliensis as
      shown by serological methods.
AB  - Lobomycosis and paracoccidioidomycosis are two different mycoses caused by Loboa
      loboi and Paracoccidioides brasiliensis, respectively. To verify cross
      antigenicity between them, lobomycosis sera were tested by immunoblotting, ELISA
      and capture-EIA against crude exo-antigen, 'cell-free antigen' and gp43 from P.
      brasiliensis. The majority of lobomycosis serum samples recognized crude exo
      antigens and gp43 from P. brasiliensis. Gp43 was eluted from an affinity column
      prepared with IgG from a patient with active lobomycosis. In lower frequencies
      and intensities, lobomycosis sera also recognized proteins of 29 kDa, 36 kDa, 39
      kDa, 52 kDa, 63 kDa, 70 kDa, 83 kDa, and 108 kDa from P. brasiliensis.

PMID- 10206753
TI  - Pathogenicity of basidiospores of Filobasidiella neoformans var. neoformans.
AB  - Basidiospores of Filobasidiella neoformans var. neoformans (progeny of
      Cryptococcus neoformans MT 100.1 x VR 45980) were able to induce cryptococcosis
      in Swiss albino mice if inoculated by intraperitoneal injection, nasal
      instillation or nasal spraying. The latter method, with the aid of a jet
      nebulizer, was first adopted to imitate the natural entrance of infectious
      particles. Using this method the small number of basidiospores (7 x 10(3)) could
      induce cryptococcosis in mice, while the higher number of the parental laboratory
      grown yeast cells (1.5 x 10(6)) did not produce infections. By nasal instillation
      Cyclophosphamide (Cy)-treated mice were more susceptible to the basidiospores,
      showing 80% cryptococcosis (eight of 10). Seven of the eight infected mice had
      disseminated cryptococcosis. Immunocompetent mice were more resistant to
      basidiospore infection than Cy-treated mice, as 40% of that group developed only
      pulmonary cryptococcosis; none had disseminated infection. Thus, we propose that
      basidiospores are one form of the infectious propagules of F. neoformans var.
      neoformans which can cause cryptococcosis, particularly in immunocompromised
      people.

PMID- 10206754
TI  - A case of subcutaneous infection in a patient with discoid lupus erythematosus
      caused by a Scytalidium synanamorph of Nattrassia mangiferae, and its treatment.
AB  - A case of subcutaneous infection caused by Scytalidium synanamorph of Nattrassia
      mangiferae is reported in a 24-year-old female suffering from subacute discoid
      lupus erythematosus. Lesions were seen on the palm of the left hand and dorsal
      aspect of the right hand. Histopathology of the biopsied specimen revealed light
      brown hyphae and single celled structures along with many inflammatory cells. The
      patient showed marked improvement with oral chloroquin and itraconazole orally
      and ketoconazole cream topically.

PMID- 10206755
TI  - Unusual pulmonary manifestations of disseminated Penicillium marneffei infection
      in three AIDS patients.
AB  - Penicillium marneffei is a rare fungal pathogen which can cause human infections
      in people predominantly living in South-east Asia and the southern portion of
      China. We report three cases of systemic P. marneffei infection in patients
      infected with HIV who lived in or had travelled to endemic areas. The clinical
      manifestation includes high fever, chills, weight loss, general malaise, chronic
      cough, haemoptysis, multiple skin lesions, abnormal liver function, etc. Chest X
      ray showed single or multiple cavitary lesions with smooth or irregular thin
      wall. P. marneffei is cultured from blood, sputum, skin biopsy, sono-guide
      aspiration and bronchoscopic biopsy. After antifungal therapy with intravenous
      amphotericin B or oral fluconazole, skin lesions resolved completely within 2
      weeks and cavitary lesions in the lungs changed to chronic fibrotic and
      interstitial processes after several months to a few years later. Our two cases
      had been treated as either pulmonary tuberculosis or suspected malignancy. A
      definite diagnosis and early treatment are important because this fungal
      infection is a marker of AIDS in South-east Asia.

PMID- 10206756
TI  - Antifungal activity of a new triazole, voriconazole (UK-109,496), compared with
      three other antifungal agents tested against clinical isolates of filamentous
      fungi.
AB  - Voriconazole is a new triazole antifungal agent with potent activity against
      yeast and moulds. We investigated the in vitro activity of voriconazole,
      itraconazole, amphotericin B and 5-flucytosine against 51 clinical isolates of
      filamentous fungi. Overall, voriconazole was active (MIC50, 0.5 mg l(-1) and
      MIC90, 8 mg l(-1)) against these mould isolates. Voriconazole was most active
      against P. boydii (MIC50, 0.12 mg l(-1)) and Aspergillus spp. (MIC90, 0.5 mg l(
      1)) and least active against Fusarium spp. (MIC90, 8 mg l(-1)) and Rhizopus spp.
      (MIC50, 8 mg l(-1)). Voriconazole was more active than amphotericin B against
      Aspergillus spp. and P. boydii. By comparison with itraconazole, voriconazole was
      more active against all isolates except Rhizopus spp. Based on these results,
      voriconazole has promising activity against commonly encountered isolates of
      filamentous fungi and its clinical usefulness should be established by further
      studies.

PMID- 10206757
TI  - In vitro activity of five antifungal agents against clinical isolates of
      Saccharomyces cerevisiae.
AB  - We evaluated the in vitro activity of fluconazole, itraconazole, ketoconazole, 5
      fluorocytosine and amphotericin B against 30 clinical isolates of Saccharomyces
      cerevisiae by a broth microdilution method, following the NCCLS recommendation.
      Testing was performed either in RPMI-1640 or yeast nitrogen base (YNB). YNB
      supported the growth of all isolates tested, while results in RPMI-1640 were not
      obtained for six isolates (20%). The MIC of all three azoles in YNB were one or
      two dilutions higher than those obtained in RPMI-1640 (P=0.0001 for fluconazole
      and itraconazole, P=0.03 for ketoconazole). Elevated MICs were observed for all
      three azoles, while all the isolates were susceptible to 5-fluorocytosine and
      amphotericin B. All MIC values were confirmed by spectrophotometric reading. Six
      strains of S. cerevisiae isolated from the faeces and consecutive blood cultures
      from an AIDS patient over a 7-month period were typed by electrophoretic
      karyotyping (EK). EK showed the maintenance of the same karyotype over time
      suggesting that the faecal isolate changed from a colonizing to infection-causing
      strain. The relative resistance of S. cerevisiae to azole drugs as well as its
      ability to cause widespread infections may promote the emergence of this species
      as a pathogen in immunosuppressed patients.

PMID- 10206758
TI  - Nonhuman primates as organ donors?

PMID- 10206759
TI  - New problems beget new solutions.

PMID- 10206760
TI  - Putting the public at risk.

PMID- 10206761
TI  - The case for using pigs.

PMID- 10206762
TI  - Speculation, stringent reasoning, and science.

PMID- 10206763
TI  - Legal and regulatory issues.

PMID- 10206764
TI  - The process of discovery.

PMID- 10206765
TI  - Xenotransplantation in Sweden.

PMID- 10206766
TI  - Stop now before it's too late.

PMID- 10206767
TI  - Current obstacles.

PMID- 10206768
TI  - The view of the Health Council of The Netherlands.

PMID- 10206769
TI  - Host-microbe interactions: bacteria. Web alert.

PMID- 10206770
TI  - Plant-microbe interactions. Affairs of the plant: colonization, intolerance,
      exploitation and co-operation in plant-microbe interactions.

PMID- 10206771
TI  - Growth and development. Web alert.

PMID- 10206772
TI  - West Pacific Joint Seminar on Clinical Microbiology.

PMID- 10206773
TI  - Limited linear range of the Abbott AxSYM serum and erythrocyte folate methods.

PMID- 10206774
TI  - More on interference of N-acetylcysteine in measurement of acetaminophen.

PMID- 10206775
TI  - Notice of duplicate publication.

PMID- 10206776
TI  - The promise of improved drug delivery.

PMID- 10206777
TI  - [Social jurisdiction: witness information and expertise/judgements].

PMID- 10206778
TI  - Alternative instrumental treatments in BPH. Introduction.

PMID- 10206779
TI  - Endoscopic ultrasonography for gallbladder disease.

PMID- 10206780
TI  - Fiber and colorectal cancer: poor relations?

PMID- 10206781
TI  - Irradiation of meat is approved, but will it be used?

PMID- 10206782
TI  - GLP-2 cloning may lead to therapy for intestinal deficiency diseases.

PMID- 10206783
TI  - The leadership of innovation.

PMID- 10206784
TI  - Image of the month. What is the etiology of these ulcers?

PMID- 10206786
TI  - Percutaneous transhepatic electrohydraulic lithotripsy for stones in biliary
      tracts.

PMID- 10206785
TI  - Management of occluded biliary Wallstents.

PMID- 10206787
TI  - Primary sclerosing cholangitis: resect, dilate, or transplant?

PMID- 10206788
TI  - Isolation and characterization of the naphthocyclinone gene cluster from
      Streptomyces arenae DSM 40737 and heterologous expression of the polyketide
      synthase genes.
AB  - Streptomyces arenae produces the aromatic polyketide naphthocyclinone, which
      exhibits activity against Gram-positive bacteria. A cosmid clone containing the
      putative naphthocyclinone gene cluster was isolated from a genomic library of S.
      arenae by hybridization with a conserved region from the actinorhodin PKS of S.
      coelicolor. Sequence analysis of a 5.5-kb DNA fragment, which hybridizes with the
      actI probe, revealed three open reading frames coding for the minimal polyketide
      synthase. A strong sequence similarity was found to several previously described
      ketosynthases, chain length factors and acyl carrier proteins from other
      polyketide gene clusters. An additional open reading frame downstream of the PKS
      genes of S. arenae showed 53% identity to act VII probably encoding an aromatase.
      Another open reading frame was identified in a region of 1.436 bp upstream of the
      PKS genes, which, however, had no similarity to known genes in the database.
      Approximately 8 kb upstream of the PKS genes, a DNA fragment was identified that
      hybridizes to an actVII--actIV specific probe coding for a cyclase and a putative
      regulatory protein, respectively. Disruption of the proposed naphthocyclinone
      gene cluster by insertion of a thiostrepton resistance gene completely abolished
      production of naphthocyclinones in the mutant strain, showing that indeed the
      naphthocyclinone gene cluster had been isolated. Heterologous expression of the
      minimal PKS genes in S. coelicolor CH999 in the presence of the act ketoreductase
      led to the production of mutactin and dehydromutactin, indicating that the S.
      arenae polyketide synthase forms a C-16 backbone that is subsequently dimerized
      to build naphthocyclinone. The functions of the proposed cyclase and aromatase
      were examined by coexpression with genes from different polyketide core
      producers.

PMID- 10206789
TI  - [Headache can often be treated by behavior therapy].

PMID- 10206790
TI  - Concerning the article by Ogata et al. Hypergonadotrophic hypogonadism in a 3
      year-old girl with blepharophimosis, ptosis, and epicanthus inversus syndrome.

PMID- 10206791
TI  - The immunogenicity and safety of a new combined diphtheria, tetanus and
      poliomyelitis booster vaccine (Td-eIPV).
AB  - In view of the continuing risk of contracting tetanus, diphtheria and
      poliomyelitis, and the well-documented decline in immunity with time, the need
      for booster vaccinations is substantial. The immunogenicity and safety of a new
      combined booster vaccine against tetanus, diphtheria and poliomyelitis (REVAXIS)
      developed by Pasteur Merieux Connaught (Lyon, France) were evaluated in four
      clinical studies. This vaccine (Td-eIPV) combines an adsorbed tetanus toxoid and
      low-dose diphtheria toxoid vaccine (Td) with an enhanced, inactivated polio
      vaccine against poliovirus types 1, 2 and 3 (eIPV). In 256 healthy young adults,
      a single dose of Td-eIPV was shown to be immunogenic, eliciting antibody levels
      considered protective against disease for each vaccine component in > or = 99.6%
      of the subjects. In 112 healthy older subjects (> 40 years of age), two doses of
      Td-eIPV elicited seroprotective levels of antibodies in 94% of the subjects for
      diphtheria, and in all subjects for tetanus and poliovirus types 1, 2 and 3.
      Safety data from all 368 subjects, as well as 31 phase I volunteers and 1,742
      subjects included in a safety study, reveal that the vaccine is safe. Most
      reactions were predictable, temporary and mild. There was no evidence that the
      vaccine was associated with any clinically serious event or modification of
      clinical laboratory parameters. The data reviewed here show that Td-eIPV is
      immunogenic and safe when administered as a booster vaccination in healthy adults
      of all ages.

PMID- 10206793
TI  - Microbiology in intraabdominal infections: what is the message for clinical
      studies? (Opinion paper).
AB  - Bacterial flora participating in intraabdominal infections are well known. Data
      are reviewed here documenting the constant antibiotic susceptibility of this
      flora despite many years of widespread use of antibiotics. The flaws inherent in
      the concept of "microbiologic efficacy" in evaluating antibiotic efficacy are
      examined. Among the possible results of a clinical trial, outcomes not in accord
      with antibiotic sensitivity data occur regularly. Factors such as host defense
      responses, source control and inoculum density also influence the outcome in a
      clinical trial but are not currently being measured. Recommendations for improved
      conduct of trails are made.

PMID- 10206792
TI  - Multisystem organ failure secondary to increased intraabdominal pressure.
AB  - Acutely increased intraabdominal pressure can lead to multisystem organ
      dysfunction. Organ dysfunction consists of acute pulmonary failure secondary to
      compressive atelectasis and associated with high peak inspiratory pressures and
      impaired gas exchange, acute renal failure with marked oliguria without
      hypernaturia, intestinal and hepatic ischemia possibly leading to bacterial
      translocation or necrosis with peritonitis, increased intracranial pressures
      which may cause brain dysfunction or aggravate head injury edema, venous
      thrombosis and thromboembolism, and abdominal wall ischemia or necrosis. The
      diagnosis is made clinically in a patient with high peak inspiratory pressures,
      oliguria and an apparently tight abdomen, although urinary bladder pressure > or
      = 20 cm H2O pressure is suggestive. However, chronically increased intraabdominal
      pressure as is seen in the morbidly obese, pregnancy and cirrhosis may be
      misleading. As to treatment, once the diagnosis is made, the patient's abdomen
      should be opened and the tension relieved. The intestinal contents need to be
      protected and evaporative water loss minimized by either closing the skin and not
      the fascia or, if this is not possible, using an impermeable protective dressing.
      If the abdomen is difficult to close at the primary operation, it is best to
      prevent the development of an acute abdominal compartment syndrome by closing
      only the skin or leaving it open and using an impermeable dressing. In
      conclusion, the acute abdominal compartment syndrome has become increasingly
      recognized as a cause for multisystem organ failure. Recognition of the problem
      or prevention is mandatory for optimal patient survival.

PMID- 10206794
TI  - Anastomic dehiscence and severe peritonitis.
AB  - Fifteen years of experience in the management of postoperative complications
      following GI surgery are reviewed. In the surgical ICU of the Hopital Saint
      Antoine, Paris, France, a referral center for these conditions, 385 cases of
      postoperative peritonitis and 500 cases of enterocutaneous fistulas were observed
      from 1980 to 1995. Original techniques of management are described in surgical
      treatment: temporary stomas, intubation irrigation of leaks situated on the upper
      GI tract, primary closure of the abdominal wall without tension. New methods of
      intensive care of intestinal conditions have also been designed: control and/or
      obturation of complex enterocutaneous fistulas, reinfusion of chyme into the
      distal small bowel and continuous enteral nutrition. In accordance with their
      experience in this field, the authors review the most controversial points of
      surgical technique and intensive care.

PMID- 10206795
TI  - Histopathology of ventilator-associated pneumonia (VAP) and its clinical
      implications.
AB  - Ventilator-associated pneumonia (VAP) is a diffuse polymicrobial and dynamic
      process, with heterogeneous distribution of lesions, showing different degrees of
      histological evolution predominating in the dependent lung zones, in which
      microbiology and histology can be dissociated. This might explain why blind
      endobronchial techniques to collect respiratory secretions have similar accuracy
      compared to visually guided samples, explaining the difficulties in validating
      any methods for its diagnosis. In the clinical setting the association of acute
      lung injury (ALI) and pneumonia is controversial. However, it is rare to detect
      diffuse alveolar damage (DAD) in absence of histological signs of pneumonia,
      probably evidencing that ALI favors the development of pneumonia.
      Histopathologically, it is difficult to distinguish initial and resolution phases
      of DAD from pneumonia and vice versa. On the other hand, there is a clear
      relationship between antimicrobial treatment and the decreased lung bacterial
      burden which strengthens the importance of distal airway sampling before starting
      antibiotic therapy.

PMID- 10206796
TI  - Proceedings of the Interplanetary Society Conference. Port Ludlow, Washington,
      USA. 30 May-2 June 1997. Dedicated to Paul B. Beeson, M.D.

PMID- 10206797
TI  - Coronal leakage of two root canal sealers containing calcium hydroxide after
      exposure to human saliva.
AB  - This in vitro study evaluated the coronal leakage of human saliva into root
      canals filled by lateral condensation of gutta-percha using two root canal
      sealers containing calcium hydroxide. Obturated canals with gutta-percha and
      either Sealapex of Sealer 26 were mounted in an apparatus and then exposed to
      saliva. The number of days required for total recontamination of the root canal
      was recorded. Evaluation was conducted for 60 days. Thirty-five percent of the
      specimens of the Sealer 26 group showed entire recontamination at 60 days. Eighty
      percent of the root canals obturated with Sealapex showed complete
      recontamination at 60 days. Sealer 26 presented significantly less leakage than
      Sealapex (p < 0.01).

PMID- 10206799
TI  - [Key points in applying statistics to toxicological tests].

PMID- 10206798
TI  - Fluorescence in situ hybridization landmarks for chromosomes of culicoides
      variipennis (Diptera: Ceratopogonidae).
AB  - Because the three chromosomes of Culicoides variipennis (Coquillett) are
      morphologically indistinguishable, physical landmarks were needed so that the
      chromosomes can be identified uniquely and oriented unambiguously before
      initiating the construction of a physical map based on FISH (fluorescence in situ
      hybridization). When repetitive sequence clones p1887 and K8.1a8 were labeled
      with digoxigenin and probe K8a.2G2 was labeled with biotin-11-dUTP and
      digoxigenin, the 3 chromosomes could be differentiated unambiguously when
      visualized with specific band-pass filters. This provided the basis for C.
      variipennis FISH landmark probes that enabled the identification and orientation
      of all 3 pairs of chromosomes. Using this multicolor FISH labeling strategy,
      probes that provide unique landmarks for the C. variipennis FISH physical map
      have been found and may be used in all FISH reactions where an unknown probe is
      placed to metaphase chromosomes of C. variipennis. A physical map of the C.
      variipennis genome will provide the foundation for map-based positional cloning
      of the gene(s) that control vector competence for the bluetongue viruses.

PMID- 10206800
TI  - [Endocrine disrupting substances (continued)--characteristic actions and test
      methods].

PMID- 10206801
TI  - ["General Toxicology" by M.J.B. Orfila (1815)].

PMID- 10206802
TI  - Dodecafluoropentane ultrasonic contrast enhancement in carotid diagnosis:
      preliminary results.
AB  - To assess the efficacy in carotid diagnosis of an investigational
      dodecafluoropentane ultrasonic contrast enhancing agent, we compared B-mode,
      color flow, and duplex Doppler findings in 16 patients with common carotid artery
      bifurcation disease after dodecafluoropentane and saline injections.
      Dodecafluoropentane produced enhanced backscatter in all patients for 4 to 20 min
      (mean, 8.4+/-4.74 min) after intravenous injection. In six patients this
      enhancement improved the color flow and pulsed Doppler signal detection in areas
      of sonographic shadowing. The enhanced color flow information changed the
      diagnostic impression in one case. Dodecafluoropentane produced enhanced
      backscatter in the carotid artery in all patients, and for a mean duration longer
      than that reported for other agents. It has the potential to improve the efficacy
      of carotid ultrasonic evaluation.

PMID- 10206803
TI  - Doppler sonographic enhancement of hepatic hemangiomas and hepatocellular
      carcinomas after perflenapent emulsion: preliminary study.
AB  - Ultrasonographic microbubble contrast agents improve Doppler signals by
      increasing blood backscatter. We retrospectively reviewed our experience with
      perflenapent (EchoGen), an emulsion of liquid dodecafluoropentane, in the
      evaluation of 13 patients with focal hepatic lesions (10 hemangiomas and six
      hepatocellular carcinomas). Perflenapent improved the detection of color Doppler
      flow signals within the lesions. The hemangiomas showed peripheral nonpulsatile
      signals and the hepatocellular carcinomas showed more diffuse enhancement with
      both arterial and venous type signals. This preliminary study suggests that
      perflenapent administration may aid in the sonographic differentiation of these
      focal lesions.

PMID- 10206804
TI  - Lack of sensitivity of endometrial thickness in predicting the presence of an
      ectopic pregnancy.
AB  - The purpose of this study was to evaluate whether endometrial thickness
      measurements can be used to differentiate between patients with ectopic pregnancy
      and spontaneous abortion. Of 676 patients with clinical suspicion of ectopic
      pregnancy, no intrauterine pregnancy was seen in 128. Of these, 42 (33%) had
      ectopic pregnancy, 52 (40%) had spontaneous abortion, and 34 (27%) had
      intrauterine pregnancy. No significant difference was found in endometrial
      thickness between women with ectopic pregnancy (mean, 9.0 mm; range, 2 to 20 mm)
      and those with spontaneous abortion (mean, 8.4 mm; range, 2 to 18 mm). A thin
      endometrium seen on transvaginal sonography cannot be used to exclude the
      diagnosis of ectopic pregnancy.

PMID- 10206805
TI  - Color Doppler waveforms of maternal cervical internal carotid arteries in
      normotensive and preeclamptic gravidas.
AB  - The objective of this study was to investigate and determine fitted percentiles
      of blood flow resistance of cervical internal carotid arteries in normal
      pregnancies from gestational weeks 20 to 42 and to compare the resistance indices
      and mean velocities of the these arteries in normotensive and preeclamptic
      gravidas. A duplex color apparatus with pulsed Doppler ultrasound scanner (7.5
      MHz) was used to determine the resistance index and mean velocity values of
      maternal cervical internal carotid arteries in 310 healthy singleton gravidas
      (group 1) and 74 singleton preeclamptic gravidas (group 2). The resistance index
      and mean velocity values of the maternal cervical internal carotid arteries
      decrease as the gestational age increases in normal gravidas, whereas in
      preeclamptic pregnancies these values are no different from those in normal
      gravidas during the second half of the gestational period.

PMID- 10206806
TI  - Sonographically guided fine needle aspiration biopsy of abdominal lymph nodes:
      experience in 102 patients.
AB  - We present our experience with sonographically guided fine needle aspiration
      biopsy of abdominal and retroperitoneal lymph nodes in 102 patients. The biopsied
      lymph nodes measured 1 to 6 cm (mean, 2.3 cm) and were located at the porta
      hepatis (n = 23), in the peripancreatic (n = 31), paraaortic (n = 22), aortocaval
      (n = 1), common iliac (n = 3), or external iliac (n = 6) regions, or in the
      mesentery (n = 16). Material sufficient for cytologic analysis was obtained in 87
      (85.2%) of the 102 patients. The cytologic diagnosis in these patients included
      malignancy in 47 patients, tuberculosis in 28 patients, reactive lymphoid
      hyperplasia in 10 patients, and aspergillosis in two patients. In the other 15
      patients, fine needle aspiration biopsy could not provide a definitive diagnosis.
      No major or minor complications occurred in our study. Thus, sonographic guidance
      is an effective alternative to computed tomography for biopsy of abdominal and
      retroperitoneal lymph nodes.

PMID- 10206807
TI  - Ovarian teratomas appearing as solid masses on ultrasonography.
AB  - The purposes of this study were to evaluate the prevalence and imaging
      characteristics of ovarian teratomas that appear as solid masses on
      ultrasonography and to compare the ultrasonographic imaging features of the
      tumors with their pathologic findings. The ultrasonographic images of 202 ovarian
      teratomas were reviewed retrospectively. Solid-appearing masses were selected
      from among them and were evaluated in terms of internal echotexture, the presence
      or lack of peripheral hypoechogenicity, posterior sonic attenuation, and tumoral
      calcification. Seventy-six (37.6%) masses of 202 belonged to the atypical solid
      appearing masses on ultrasonography. Of 76 masses, 57 (75.0%) had peripheral
      hypoechogenicity; 38 masses had well-defined thin hypoechoic rims, whereas 19 had
      poorly demarcated peripheral hypoechogenicity. Posterior sonic attenuation was
      evident in 18 (23.7%) masses. The presence of peripheral hypoechogenicity, which
      is suggestive of the fluid portion of the tumor, might be one of the
      characteristic findings of solid-appearing ovarian teratomas on ultrasonography.

PMID- 10206808
TI  - Extended field of view sonography in musculoskeletal imaging.
AB  - The usage patterns and benefits of extended field of view sonography were
      analyzed prospectively in 100 consecutive musculoskeletal ultrasonographic
      examinations. Extended field of view sonography was used in 23 of 58 abnormal
      cases (10 of 41 shoulders, five of eight other joints, seven of seven extra
      articular extremities, one of two interventional procedures) and two of 42 normal
      cases. Of 23 abnormal cases using extended field of view sonography (12 of 46
      tendon tears and 11 of 12 fluid collections or masses), this modality helped in
      measuring abnormalities in 13, displaying abnormalities in 19, showing spatial
      relationships in 17, communicating findings in 13, and making diagnoses in 0.
      Extended field of view is a useful technique for musculoskeletal ultrasonography.
      The primary benefits are measuring and displaying abnormalities (most often fluid
      collections or masses and extra-articular extremity abnormalities).

PMID- 10206809
TI  - Variation in echogenicity of the basal ganglia: anisotropic effect.
AB  - We observed that the fetal brain demonstrates relatively increased echogenicity
      of the basal ganglia compared with the thalami and cortical brain parenchyma,
      which we did not observe on neonatal sonograms. We hypothesized that the
      difference in relative echogenicity was due to differences in imaging techniques
      and anisotropic effects for prenatal and postnatal brain images. In 18
      consecutive neonates, we obtained coronal images of the basal ganglia and thalami
      through the anterior fontanelle and axial images through the anterolateral
      fontanelle with both 5 and 7.5 MHz transducers. Two observers determined whether
      increased echogenicity or conspicuity of the basal ganglia was present, comparing
      the axial and coronal planes. We observed relatively increased echogenicity of
      the basal ganglia in the axial plane in 11 of the 16 examinations in this series.
      Of these 11, the increased echogenicity effect was manifest only in the axial
      plane in seven neonates. In the four instances in which the increased basal
      ganglia echogenicity was seen in both the coronal and axial planes, the effect
      was better shown in axial plane in all four. We did not observe any cases of
      increased echogenicity of the basal ganglia only in the coronal plane. The
      increased echogenicity was more conspicuous with the lower frequency transducer
      in 10 of the 11 examinations. We believe that the change in echogenicity of the
      basal ganglia is predominantly an anisotropic effect. Observing that increased
      echogenicity of the basal ganglia can disappear or decrease when comparing images
      in the axial to the coronal plane or be better demonstrated with lower frequency
      transducers might be a means by which to distinguish this phenomenon from true
      pathologic processes of the neonatal brain.

PMID- 10206810
TI  - Ultrasonographic guidance for injections of local steroids in the native hip.

PMID- 10206811
TI  - Abnormal skull shape in intrauterine growth retardation: report of two cases.

PMID- 10206812
TI  - Prenatal diagnosis of tuberous sclerosis in monozygotic twins with cardiac
      masses.

PMID- 10206813
TI  - AIUM technical bulletin. Transducer manipulation. American Institute of
      Ultrasound in Medicine.

PMID- 10206814
TI  - Color Doppler sonography of focal lesions of the skin and subcutaneous tissue.
AB  - We evaluated with color Doppler sonography 71 visible and palpable nodules of the
      skin and subcutaneous tissue from 51 patients. The nodules were classified as
      avascular (type I), hypovascular with a single vascular pole (type II),
      hypervascular with multiple peripheral poles (type III), and hypervascular with
      internal vessels (type IV). Of the 32 malignant nodules, 9% showed a type I
      pattern, 50% had a type III pattern, and 41% had a type IV pattern; of the 39
      benign nodules, 86% showed a type I pattern and 14% had a type II pattern. The
      sensitivity and specificity of hypervascularity in malignant lesions were 90% and
      100%, respectively, whereas the sensitivity and specificity of hypovascularity in
      benign lesions were 100% and 90%, respectively. The authors conclude that color
      Doppler sonography is able to increase the specificity of ultrasonography in the
      evaluation of nodular lesions of the skin.

PMID- 10206815
TI  - Clinical significance of first trimester umbilical cord cysts.
AB  - A cystic mass of the umbilical cord was identified by transvaginal sonography in
      10 first trimester pregnancies at a mean gestational age of 8 weeks 4 days
      (range, 8 weeks 1 day to 9 weeks 3 days) and at a mean crown-rump length of 20.5
      mm (range, 15 to 25 mm). The cyst was solitary in all cases, the mean diameter
      was 4.6 mm (range, 3 to 6 mm), and the location was closer to the fetal insertion
      in two cases, in the middle of the cord in seven cases, and closer to the
      placental insertion in one case. Gestational sac and yolk sac diameters as well
      as the fetal heart rate were within normal ranges for gestational age in all
      cases. Information on detailed second trimester scans was available in nine
      cases, demonstrating complete resolution of the cyst and normal fetal anatomic
      survey in each case. These nine pregnancies were followed to delivery, and normal
      healthy infants were delivered at term in all cases. This series suggests that
      the incidental detection of umbilical cord cysts in early pregnancy is not
      associated with an adverse pregnancy outcome.

PMID- 10206816
TI  - Online journals: features, usage, access.

PMID- 10206817
TI  - 1998 annual meeting of the Association for Gnotobiotics.

PMID- 10206818
TI  - Lovelace Respiratory Research Institute annual symposium: validity of animal
      models of human respiratory diseases.

PMID- 10206819
TI  - The basal ganglia and portal-systemic encephalopathy.
AB  - Despite decades of research, the pathogenesis of portal-systemic encephalopathy
      (PSE) remains puzzling. Current hypotheses on the pathophysiology of PSE usually
      deal with metabolic toxins like ammonia or disturbances in neurotransmitter
      systems, especially glutamatergic or GABA-ergic neurotransmission. With respect
      to clinical, neuropathological, MRI and PET findings this review advances the
      hypothesis that the known alterations of neurotransmission and astrocytic
      function in PSE might impair basal ganglia function in cirrhotics. The symptoms
      of PSE - whether cognitive, emotional or motor - are proposed to be a consequence
      of basal ganglia dysfunction.

PMID- 10206820
TI  - Cerebral magnetic resonance imaging in patients with chronic liver disease.
AB  - Bilateral, symmetrical hyperintensity of the globus pallidus is observed in T1
      weighted cerebral magnetic resonance images in from 52 to 100% of patients with
      chronic liver disease. No significant relationship exists between the presence of
      these cerebral changes in image signal intensity and the patients'
      neuropsychiatric status. However, their presence significantly relates to both
      the severity of the liver disease and the presence and degree of portal-systemic
      shunting of blood. This shortening of the T1-relaxation time is associated with
      pallidal deposition of manganese most likely reflecting the presence of an
      adaptive process designed to improve the efficacy of ammonia detoxification by
      astrocytes. Future studies employing magnetic resonance imaging techniques to
      obtain information on cerebral function or combined with magnetic resonance
      spectroscopy to obtain localized biochemical information might further our
      understanding of the pathogenesis of hepatic encephalopathy in cirrhotic
      patients.

PMID- 10206821
TI  - Proton magnetic resonance spectroscopy in portal-systemic encephalopathy.
AB  - Localized proton magnetic resonance spectroscopy (MRS) with short echo times
      provides unique information of human cerebral metabolism. Studies on patients
      with portal-systemic encephalopathy (PSE) have been performed to clarify the
      pathogenesis of this disease and to find a method which allows an objective
      diagnosis. Spectra of patients with PSE show typical abnormalities. Regional
      variations of these spectral changes are observed. The metabolic changes
      correlate with the grade of encephalopathy but the dependence on the Child-Pugh
      score is controversial. No causal dependence between MRS findings and
      abnormalities in magnetic resonance imaging is evident. Differences in magnetic
      resonance spectra in patients compared to controls vanish after liver
      transplantation, but increase after TIPS. The results of proton magnetic
      resonance spectroscopy are important for an understanding of the pathogenesis of
      PSE, but do not aid in the diagnosis of subclinical hepatic encephalopathy.

PMID- 10206822
TI  - Positron emission tomography in the study of hepatic encephalopathy.
AB  - Positron-emission tomography (PET) is a quantitative technique that produces
      images of biological or physiological processes. The nature of the image depends
      on the tracer used: common tracers used to study HE include 18F
      fluordeoxyglucose, a marker of glucose metabolism; 15O-water, a marker of
      cerebral blood flow; and 13N-ammonia, a marker of ammonia metabolism. Combined
      blood flow and ammonia metabolism studies can be used to calculate the
      permeability surface area product for ammonia at the blood brain barrier. To take
      full advantage of PET, the data should be analyzed using one of the several
      sophisticated image processing and analysis techniques that are available. Thus,
      PET is an ideal technique to evaluate ammonia metabolism and, because of a close
      linkage of blood flow and glucose metabolism with neural activity, to investigate
      the neural response to drugs and other treatments and to examine neural systems
      that mediate specific tasks that are impaired in patients with HE.

PMID- 10206823
TI  - Role of manganese in the pathogenesis of portal-systemic encephalopathy.
AB  - Amongst the potential neurotoxins implicated in the pathogenesis of hepatic
      encephalopathy, manganese emerges as a new candidate. In patients with chronic
      liver diseases, manganese accumulates in blood and brain leading to pallidal
      signal hyperintensity on T1-weighted Magnetic Resonance (MR) Imaging. Direct
      measurements in globus pallidus obtained at autopsy from cirrhotic patients who
      died in hepatic coma reveal 2 to 7-fold increases of manganese concentration. The
      intensity of pallidal MR images correlates with blood manganese and with the
      presence of extrapyramidal symptoms occurring in a majority of cirrhotic
      patients. Liver transplantation results in normalization of pallidal MR signals
      and disappearance of extrapyramidal symptoms whereas transjugular intrahepatic
      portosystemic shunting induces an increase in pallidal hyperintensity with a
      concomitant deterioration of neurological dysfunction. These findings suggest
      that the toxic effects of manganese contribute to extrapyramidal symptoms in
      patients with chronic liver disease. The mechanisms of manganese neurotoxicity
      are still speculative, but there is evidence to suggest that manganese deposition
      in the pallidum may lead to dopaminergic dysfunction. Future studies should be
      aimed at evaluating the effects of manganese chelation and/or of treatment of the
      dopaminergic deficit on neurological symptomatology in these patients.

PMID- 10206826
TI  - Does ammonia contribute to increased GABA-ergic neurotransmission in liver
      failure?
AB  - The ammonia and GABAergic neurotransmission hypotheses of the pathogenesis of
      hepatic encephalopathy (HE) have appeared to be unrelated and perhaps mutually
      exclusive. Observations in animal models of fulminant hepatic failure, that are
      consistent with increased GABAergic inhibitory neurotransmission contributing to
      the manifestations of HE, include: (i) abnormal visual evoked potential waveforms
      that resemble those induced by GABA(A)/benzodiazepine (BZ) receptor complex
      agonists; (ii) GABA(A)/BZ receptor complex antagonist-induced ameliorations of
      encephalopathy; (iii) increased resistance to drugs which decrease GABAergic
      tone; and (iv) hypersensitivity of CNS neurons to depression by GABA(A)/BZ
      receptor complex agonists. Mechanisms of increased GABAergic tone in HE may
      include the following: (i) increased brain concentrations of natural BZs; and
      (ii) increased GABA concentrations in synaptic clefts, possibly due to increased
      blood-brain-barrier permeability to GABA and a decrease in GABA(B) receptor
      density. Both neuroelectrophysiological and behavioral data indicate that ammonia
      concentrations in the range 0.75-2 mM induce increased excitatory
      neurotransmission. In contrast, recently, ammonia concentrations in the range
      0.15-0.75 mM, i.e. concentrations that commonly occur in plasma in precoma HE,
      have been shown: (i) to increase GABA-induced chloride current in cultured
      neurons; and (ii) to enhance synergistically the binding of GABA(A)/BZ receptor
      agonists. In addition, increased ammonia concentrations enhance synthesis of
      neurosteroids in astrocytes, and some neurosteroids potently augment GABAergic
      neurotransmission. Thus, the modestly elevated concentrations of ammonia, that
      commonly occur in liver failure, may contribute to the manifestations of HE by
      enhancing GABAergic inhibitory neurotransmission. This concept appears to unify
      the ammonia and GABAergic neurotransmission hypotheses.

PMID- 10206825
TI  - Alterations of neurotransmitter-related gene expression in human and experimental
      portal-systemic encephalopathy.
AB  - Portal-systemic encephalopathy (PSE) is a serious neuropsychiatric condition that
      results from chronic liver failure and portal-systemic shunting of venous blood.
      PSE is particularly prevalent following treatment of portal hypertension or
      ascites by the TIPS procedure. Recent studies both in autopsied brain tissue from
      PSE patients as well as in experimental animal models of PSE reveal that chronic
      liver failure results in altered expression of several genes coding for proteins
      having key roles in the control of neuronal excitability. Such alterations
      include increased expression of monoamine oxidase (MAO-A isoform), the
      "peripheral-type" benzodiazepine receptor (PTBR) as well as constitutive,
      neuronal nitric oxide synthase (nNOS). Such changes result in altered protein
      expression and in increased degradation of monoamine neurotransmitters, increased
      synthesis of neurosteroids with inhibitory properties and increased production of
      nitric oxide (respectively) in brain in chronic liver failure. In the case of
      PTBR and nNOS, increases in expression result from exposure to ammonia and/or
      manganese, two neurotoxic agents shown previously to be increased in brain in
      chronic liver failure. Further elucidation of the consequences of
      neurotransmitter-related gene expression could identify new pathophysiologic
      mechanisms and result in new approaches to the prevention of PSE in chronic liver
      disease in humans.

PMID- 10206827
TI  - Neuropsychological aspects of portal-systemic encephalopathy.
AB  - An extensive psychometric test program was performed in 96 patients with proven
      liver cirrhosis and clinical signs of portal hypertension as well as in 20
      patients with alcoholic pancreatitis, in 19 patients without cirrhosis but with
      alcoholic cerebral atrophy and in 163 normal controls. The study population
      comprised six groups of subjects as follows: Group 1. 27 patients with non
      alcoholic cirrhosis and normal EEG pattern. Group 2. 48 patients with alcoholic
      cirrhosis and normal EEG pattern. Group 3. 21 patients with cirrhosis and minimal
      EEG changes. Group 4. 20 patients with alcoholic pancreatitis. Group 5. 19
      patients without cirrhosis but with alcoholic cerebral atrophy. Group 6. 163
      normal controls. A one way analysis of variances comparing asymptomatic patients
      (group 1, 2 and 4) with controls (group 6) revealed no significant differences
      between patients with alcoholic and non-alcoholic cirrhosis, both cirrhotic
      groups scoring significantly lower than patients with alcoholic pancreatitis and
      normal controls, who did not differ significantly. Comparing symptomatic patients
      (group 3 and 5) with normal controls both patient groups scored significantly
      lower than controls, the cirrhotic group (group 3) scoring significantly lower
      than patients with alcoholic cerebral atrophy. A two way analysis of variances
      revealed that in clinically asymptomatic patients cerebral functional defects
      revealed by psychometry are only due to cirrhosis and that in patients with
      clinical evidence of cerebral impairment the factors alcohol and cirrhosis are
      additive - not synergistic. A multiple group stepwise discriminant analysis
      revealed that tests evaluating psychomotor functions contributed most to the
      discrimination. Especially "line tracing " proved to be most sensitive and most
      specific followed by dexterity, steadiness, aiming, digit symbols in sensitivity
      and by reaction time, steadiness and dexterity in specificity. A test program for
      clinical use is proposed.

PMID- 10206824
TI  - Astroglial dysfunction in hepatic encephalopathy.
AB  - While the pathogenesis of hepatic encephalopathy (HE) remains elusive, there is
      considerable evidence pointing to a key role of ammonia-induced dysfunction of
      astrocytes in this condition. Deficits in the ability of astrocytes to take up
      glutamate from the extracellular space may lead to abnormal glutamatergic
      neurotransmission. Furthermore, excessive stimulation of neuronal and glial
      glutamate receptors by elevated extracellular levels of glutamate may lead to
      excitotoxicity and greater glial dysfunction. Ammonia also causes upregulation of
      astroglial peripheral-type benzodiazepine receptors (PBRs) which is associated
      with increased production of neurosteroids. These neurosteroids have potent
      positive modulatory effects on the neuronal GABA(A) receptor which, combined with
      an ammonia-induced astroglial defect in GABA uptake, may result in enhanced
      GABAergic tone. Brain edema, associated with fulminant hepatic failure, may also
      result from astroglial abnormalities as the edema appears to be principally
      caused by swelling of these cells. Increased amounts of glutamine in astrocytes
      resulting from elevated brain ammonia levels may be a factor in this swelling.
      Other osmolytes such as glutathione may also be involved. Glial swelling may also
      result from NH4+ - and K+ -mediated membrane depolarization as well as by the
      actions of PBR agonists and neurosteroids. These findings show that an ammonia
      induced gliopathy is a major factor in the pathogenesis of HE.

PMID- 10206828
TI  - Psychiatric aspects of portal-systemic encephalopathy.
AB  - This paper focuses on psychiatric aspects of portal-systemic encephalopathy (PSE)
      due to chronic liver disease and/or portal-systemic shunting. Clinical syndromes
      of PSE are discussed from the point of view of biological psychiatry, but,
      psychological consequences of concomitant cognitive disorders are also addressed.
      Psychiatric symptoms of early PSE and sleep disorders in patients with chronic
      liver disease are of specific interest.

PMID- 10206829
TI  - Informed consent and approval by institutional review boards in published reports
      on clinical trials.

PMID- 10206830
TI  - Pravastatin and coronary heart disease.

PMID- 10206831
TI  - Pravastatin and coronary heart disease.

PMID- 10206832
TI  - Implantable defibrillators, pacemakers, and electronic antitheft devices.

PMID- 10206833
TI  - Implantable defibrillators, pacemakers, and electronic antitheft devices.

PMID- 10206834
TI  - Management of acoustic neuroma.

PMID- 10206835
TI  - Management of acoustic neuroma.

PMID- 10206836
TI  - Management of acoustic neuroma.

PMID- 10206837
TI  - Adrenal lymphocytic infiltration and adrenocortical tumors in a patient with 21
      hydroxylase deficiency.

PMID- 10206838
TI  - Gentamicin contaminated with endotoxin.

PMID- 10206839
TI  - Case 35-1998: use of lithium to prevent corticosteroid-induced mania.

PMID- 10206840
TI  - Hallux rigidus and atrophy of calf muscles.

PMID- 10206841
TI  - Large hepatic hematoma and intraabdominal hemorrhage associated with abuse of
      anabolic steroids.

PMID- 10206842
TI  - Combination therapy for hepatitis C infection.

PMID- 10206843
TI  - Combination therapy for hepatitis C infection.

PMID- 10206844
TI  - Carotid endarterectomy.

PMID- 10206845
TI  - Carotid endarterectomy.

PMID- 10206847
TI  - Carotid endarterectomy.

PMID- 10206848
TI  - Toxic erythroderma due to ticlopidine.

PMID- 10206846
TI  - Carotid endarterectomy.

PMID- 10206850
TI  - Bragdon v. Abbott: the Americans with Disabilities Act and HIV infection.

PMID- 10206849
TI  - Bragdon v. Abbott: the Americans with Disabilities Act and HIV infection.

PMID- 10206852
TI  - Legal struggles in the world of medicine.

PMID- 10206851
TI  - Bragdon v. Abbott: the Americans with Disabilities Act and HIV infection.

PMID- 10206853
TI  - Human granulocytic ehrlichiosis in western Europe.

PMID- 10206854
TI  - [The dynamics of the ectoparasite count and the protein level in the blood serum
      of infested carp under experimental conditions].
AB  - Carps of one and two years age used for laboratory experiments were collected in
      winter time. 7 groups of carps of one year age were examined each 10th day during
      70 days and 5 groups of two years age were examined each 15 days during 75 days.
      In carps of one year age the increase of different parasites was observed in
      different time: Dactylogyrus extensus--after 40 and 70 days, Icthyophthirius
      multifiliis--after 50 days, Trichodina sp.--after 60 days. In carps of two years
      age the increase of all parasite groups observed after 45 days, extremely great
      number of D. extensus was recorded after 60-70 days. Contents of proteins in a
      blood plasma of both age groups of carps is reliably decreased when the number of
      parasites is increased. Fluctuations of parasite abundance on the body and gills
      and some morphophysiological indices in carps of one year age in a control and in
      conditions of starvation were examined.

PMID- 10206856
TI  - Observers of childhood sexual behavior.

PMID- 10206855
TI  - [The family Tetraonchidae (Monogenea): its structure and position among the
      monogeneans].
AB  - The muscle fascicles of the haptor in Tetraonchus monenteron have been described.
      The muscle connection of the fan-shaped dorsal bars with dorsal anchors is shown.
      When these muscle fascicles are contracted the dorsal anchors works as pincers.
      The division of tetraonchids into two genera based on types of copulatory organs,
      morphology of bars and haptor ans associations with different groups of fishes is
      restored. Different authors based on ciliated cells and chaetotaxy of the
      oncomiracidium and comparative spermiogenetic of T. monenteron include the
      tetraonchids with 16 marginal hooks into the order Dactylogyroidea. In the same
      time, based on the analysis of the onthogenesis of the dactylogyrid's haptor they
      postulate, that the haptor of these worms originally had 2 pairs of anchors and
      only 14 marginal hooks. The present paper contains data indicating that different
      representatives of the Dactylogyridea have 14-18 marginal hooks. Author put
      forward a suggestion, that some group of dactylogyrids originally did not have
      the anchors.

PMID- 10206857
TI  - Early menarche in Japanese Down syndrome.

PMID- 10206858
TI  - Physician's duty to warn third parties about the risk of genetic diseases.

PMID- 10206860
TI  - Can drowning in swimming pools be prevented?

PMID- 10206859
TI  - Can drowning in swimming pools be prevented?

PMID- 10206861
TI  - Cisapride and proarrhythmia in childhood.

PMID- 10206862
TI  - Crazy Glue and foreign bodies.

PMID- 10206864
TI  - Genetic clues revise view of Japanese roots.

PMID- 10206863
TI  - New clues found to diabetes and obesity.

PMID- 10206865
TI  - Lyme disease. Patients scarce in test of long-term therapy.

PMID- 10206866
TI  - Harnessing the power of stem cells.

PMID- 10206867
TI  - Stem cells profile. A man in a hurry.

PMID- 10206868
TI  - Can mitochondrial clocks keep time?

PMID- 10206869
TI  - Y chromosomes point to Native American Adam.

PMID- 10206870
TI  - Physician-scientists at risk.

PMID- 10206871
TI  - Physician-scientists at risk.

PMID- 10206872
TI  - Physician-scientists at risk.

PMID- 10206873
TI  - Physician-scientists at risk.

PMID- 10206874
TI  - Arsenic and drinking water contamination.

PMID- 10206875
TI  - Crystal-growing in space.

PMID- 10206876
TI  - Exon shuffling in retrospect.

PMID- 10206877
TI  - Putting stem cells to work.

PMID- 10206878
TI  - Martian climate. A message from warmer times.

PMID- 10206879
TI  - Academic sequencers challenge Celera in a sprint to the finish.

PMID- 10206880
TI  - From a flatworm, new clues on animal origins.

PMID- 10206881
TI  - Key molecular signals identified in plants.

PMID- 10206882
TI  - Genetic study shakes up out of Africa theory.

PMID- 10206883
TI  - Sweden considers more oversight of research.

PMID- 10206884
TI  - Nabel to head NIH Vaccine Research Center.

PMID- 10206885
TI  - Cancer research. A surprising partner for angiostatin.

PMID- 10206886
TI  - Nurture helps mold able minds.

PMID- 10206887
TI  - Forging a link between biofilms and disease.

PMID- 10206888
TI  - Science over politics.

PMID- 10206889
TI  - Free electrons?

PMID- 10206890
TI  - Monkey numeration.

PMID- 10206891
TI  - Dissecting dendrite dynamics.

PMID- 10206892
TI  - Techview: DNA sequencing. Sequencing the genome, fast.

PMID- 10206893
TI  - Polymer chemistry. Designer jell-o.

PMID- 10206896
TI  - Fossil offers a glimpse into mammals' past.

PMID- 10206894
TI  - Crystal structure of human ZAG, a fat-depleting factor related to MHC molecules.
AB  - Zn-alpha2-glycoprotein (ZAG) is a soluble protein that is present in serum and
      other body fluids. ZAG stimulates lipid degradation in adipocytes and causes the
      extensive fat losses associated with some advanced cancers. The 2.8 angstrom
      crystal structure of ZAG resembles a class I major histocompatibility complex
      (MHC) heavy chain, but ZAG does not bind the class I light chain beta2
      microglobulin. The ZAG structure includes a large groove analogous to class I MHC
      peptide binding grooves. Instead of a peptide, the ZAG groove contains a
      nonpeptidic compound that may be implicated in lipid catabolism under normal or
      pathological conditions.

PMID- 10206895
TI  - Plant science. Data in key papers cannot be reproduced.

PMID- 10206897
TI  - Chinese center sues over study coverage.

PMID- 10206898
TI  - UN to end Children's Vaccine Initiative.

PMID- 10206899
TI  - Scientific publications. The march of paradigms.

PMID- 10206900
TI  - NIH invites activists into the inner sanctum.

PMID- 10206901
TI  - Did cooked tubers spur the evolution of big brains?

PMID- 10206902
TI  - A potential phosphate crisis.

PMID- 10206903
TI  - Origin of the Amerindians.

PMID- 10206904
TI  - Interdisciplinary research at NIH.

PMID- 10206905
TI  - Aging and the genome.

PMID- 10206906
TI  - Cave painting hazard?

PMID- 10206907
TI  - Peptide bond formation: retraction.

PMID- 10206908
TI  - Genetic enhancement in humans.

PMID- 10206909
TI  - Mix and match in the tree of life.

PMID- 10206911
TI  - Highly visible, curiously intangible.

PMID- 10206910
TI  - Crosstalk between Rac and Rho.

PMID- 10206912
TI  - The Fox Chase Cancer Center and Free University Hospital Investigators' Workshop
      and Consensus Conference on Paclitaxel. St. Thomas, U.S.Virgin Islands, March 25
      29, 1998. Proceedings and abstracts.

PMID- 10206913
TI  - [An addendum to the article by C. Rodel, W. Hohenberger, R. Sauer. Adjuvant and
      neoadjuvant radiochemotherapy of rectal carcinoma. Strahlenther Onkol 1998; 174:
      497-504 (Nr. 10)].

PMID- 10206915
TI  - Proceedings of the Jean Borel Symposium. Future prospects for immunomodulation.
      Florence, Italy, February 16, 1998.

PMID- 10206916
TI  - European Gastro Club 30th Conference. Munster, 2-3 October 1998. Abstracts.

PMID- 10206914
TI  - [Is tamoxifen effectively preventive against breast carcinoma?].

PMID- 10206917
TI  - [Workshop on quality management in rheumatology. Eisenach, 22-24 May 1998.
      Abstracts].

PMID- 10206918
TI  - Epidemiological surveillance for the spread of HIV infection. Foreword.

PMID- 10206919
TI  - A salute to Torsten Gordh, 90.

PMID- 10206920
TI  - Avascular necrosis. Congress Orthopaedica Belgica. Brussels, June 5-6, 1997.

PMID- 10206921
TI  - Primary Prevention of Colorectal Cancer and Polyps: Does Fiber have a Role?
      Proceedings of a symposium. New York City, New York, USA. December 2, 1997.

PMID- 10206922
TI  - Role of androgens in the menopause. Proceedings of a symposium. New York, New
      York, USA. April 18, 1998.

PMID- 10206923
TI  - [When will evidence-based medicine (EBM) reach surgical activities? For a
      cultural change].

PMID- 10206924
TI  - [Reflections on gifts from the pharmaceutical industry].

PMID- 10206925
TI  - Special issue dedicated to Dr. Peter Ivanovich's contributions to the
      International Society for Artificial Organs.

PMID- 10206926
TI  - Certification vital.

PMID- 10206927
TI  - The transoceanic air evacuation of unstable angina patients.
AB  - BACKGROUND: The United States Air Force (USAF) air evacuation system in the
      Western Pacific frequently transports unstable angina patients on fixed wing
      aircraft over long distances to reach definitive cardiologic and cardiothoracic
      capabilities. This study begins to answer the question: Does the transfer of
      unstable angina (i.e., crescendo angina or rest angina) patients over long
      distances adversely affect the overall outcome of such patients? METHODS: A case
      series study was conducted by obtaining a list of urgent and priority unstable
      angina patients from the Pacific theater from January 1992 through December 1996.
      Each of these patients' inpatient records were reviewed for cardiac
      catheterization (cath) result, ejection fraction (EF), previous cardiac history,
      angioplasty (PTCA) procedures, coronary artery bypass graft (CABG) surgery, and
      whether a patient had congestive heart failure (CHF), myocardial infarction (MI),
      death or other complications on this admission. RESULTS: Of the 59 records
      reviewed, 61% (36/59) had coronary artery disease (CAD) of at least one vessel
      greater than 90% occlusion, 31% (18/59) had PTCA, 24% (14/59) had a CABG, 5%
      (3/59) had CHF, 3% (2/59) had an MI, 24% had some type of a complication, and
      1.7% (1) died on this admission. CONCLUSION: Patients with significant CAD seem
      to tolerate air transport well with relatively few complications considering the
      overall morbidity and mortality associated with the diagnosis of unstable angina.

PMID- 10206928
TI  - A comprehensive noise survey of the S-70A-9 Black Hawk helicopter.
AB  - PURPOSE: This paper reports the results of a comprehensive noise survey of the
      Sikorsky S-70A-9 Black Hawk helicopter environment and provides an assessment of
      the hearing protection devices worn by Australian Army personnel exposed to that
      environment. METHODS AND RESULTS: At-ear noise levels were measured at 4
      positions in the cabin of the Black Hawk under various flight conditions and at
      13 positions outside the Black Hawk under various ground running conditions using
      the Head Acoustic Measurement System (Head, GmbH). The attenuation properties of
      the hearing protection devices (HPDs) normally worn by aircrew and maintenance
      crews (the ALPHA helmet and the Roanwell MX-2507 Communications headset) were
      also assessed. At-ear sound pressure levels that would be experienced by
      personnel wearing their normal HPDs were determined at the positions they would
      normally occupy in and around the aircraft. CONCLUSION: Results indicate that
      HPDs do not provide adequate hearing protection to meet current hearing
      conservation regulations which allow a permissible noise exposure of 85 dB(A) for
      an 8-h day.

PMID- 10206929
TI  - Drinking and flying: a structural model.
AB  - BACKGROUND: Under a recent revision of the European Joint Aviation Authorities
      operations regulations it has been prohibited to act as a crew member of an
      aircraft with a BAC of greater than 0.02%. METHODS: This survey of UK Civil
      Aviation Authority pilots suggests that over 50% of respondents may have flown an
      aircraft with a BAC of greater than this prescribed amount. RESULTS: Professional
      pilots were found to be heavier drinkers than private pilots and were also more
      likely to infringe the 0.02% BAC rule. CONCLUSION: Analysis of the data using
      path analysis suggests that professional pilots may be more prone to offending as
      a result of training in a "drinking culture" and as a response to commercial
      pressures in the industry.

PMID- 10206930
TI  - Is residual impairment after alcohol an effect of repeated performance?
AB  - BACKGROUND: The study examines the residual impairment of performance due to
      alcohol on the descending limb of the blood alcohol curve. The occurrence of
      residual impairment at low or zero levels of blood alcohol is well established
      but its cause is uncertain. It is hypothesized that residual impairment may be
      due in part to the methodological procedure of repeated performance testing in
      the post-ingestion period. METHODS: There were 80 volunteers randomly allocated
      to one of four treatment conditions: a) alcohol and repeated performance (A-R)
      where psychomotor tasks were performed at 20-min interval for 2 h post ingestion;
      b) alcohol and double performance (A-D) where tasks were performed only at 1 h
      and 2 h from ingestion; c) placebo and repeated performance (P-R); and d) placebo
      and double performance (P-D). Alcohol was administered as vodka to achieve a peak
      blood-alcohol concentration (BAC) of approximately 80 mg per 100 ml. Performance
      effects were assessed by a dual task of primary pursuit tracking and secondary
      visual reaction time, and a visual sustained attention task. RESULTS: Alcohol
      caused significant impairment of secondary reaction time, the effect being
      greatest at peak BAC. Sustained attention was also impaired by alcohol but the
      effect just missed significance. Repeated performance conditions were associated
      with significantly greater impairment of secondary reaction time and sustained
      attention when compared with double performance conditions. The factor of
      performance condition did not, however, interact with that of alcohol.
      CONCLUSIONS: The monotony and boredom that may be associated with repeated
      performance do not contribute to residual alcohol impairment.

PMID- 10206931
TI  - The relationship of physical fitness on pilot candidate selection in the Israel
      Air Force.
AB  - BACKGROUND: The purpose of this study was to examine whether physical fitness is
      an important component in the selection process of pilot candidates to the Israel
      Air Force (IAF) flight school. METHODS: There were 223 male pilot candidates who
      volunteered to participate in the study. All subjects were tested 1 - 12 wk prior
      to a week-long "bootcamp" for aerobic power (Astrand bicycle test), anaerobic
      power (vertical jump test), and percent body fat. In addition, an activity
      profile was established based on an activity history questionnaire. All fitness
      measures were correlated to a performance score based on the IAF selection
      criteria measure for each candidate. RESULTS: Candidates who were accepted to
      flight school had a higher aerobic capacity, anaerobic power output relative to
      body weight and a lower percent body fat than candidates who were not successful.
      Significant correlations were seen between the performance score and aerobic
      power (r = 0.31), anaerobic power (r = 0.17) and anaerobic power relative to body
      weight (r = 0.21). Linear regression analysis showed that aerobic power explained
      9% of the variance in the performance score, while anaerobic power explained an
      additional 3%. The results of this study suggest that physical fitness has a
      positive influence on the success of pilot candidates in gaining admittance to
      the IAF flight school.

PMID- 10206932
TI  - The epidemiology of cold injury in Antarctica.
AB  - METHOD: A retrospective study was performed of 10 yr of medical records to
      determine the type, severity, etiological factors and treatment of cold injury
      experienced by members of the British Antarctic Survey between 1986-95. RESULTS:
      There were 61 new consultations for cold injury. These comprised 2.5% of all new
      consultations with an incidence of 65.6 per 1000 per year. Cold injuries seen
      were frostbite (95%), hypothermia (3%) and trench foot (2%). Superficial
      frostbite was the most common injury (74% of cases) with the face the most
      frequently affected area (47% of injuries). No cases of frostbite severe enough
      to cause permanent tissue loss were seen. The prevalence of cold injury increased
      with falling temperature to a maximum between -25 and -35 degrees C, despite
      these temperatures occurring infrequently. The relationship with windchill is not
      as clear cut with frequency of injury tending to follow the frequency of
      windchill values except at higher windchill values. Neither temperature nor
      windchill were found to significantly influence the severity of frostbite. Prior
      cold injury was shown to be significantly (chi2 p < 0.001) associated with
      further cold injury. Most injuries (78%) occurred during recreation; skiing and
      snowmobile driving were often implicated. CONCLUSIONS: Cold injury is uncommon in
      Antarctica. Despite this, it warrants a continued high profile as under most
      circumstances it may be regarded as an entirely preventable occurrence.

PMID- 10206933
TI  - Three cases of spinal decompression sickness treated by U.S. Navy Treatment Table
      7.
AB  - For patients of type 2 decompression sickness, recompression therapy using U.S.
      Navy Treatment Table 6 (TT6) and its extensions is the most common means of
      treatment. However, some cases are resistant to the recompression therapy, and
      the outcome of TT6 is not always satisfactory. Although a new table, the U.S.
      Navy Treatment Table 7 (TT7) was described in 1985 in the U.S. Navy Diving
      Manual, to date few cases who were treated using TT7 have been reported. Here, we
      report three cases of spinal decompression sickness who received treatment
      according to TT7. Two were sports scuba divers, and the other a commercial diver.
      TT7 was applied later than 4 d after onset in all three cases; two patients were
      remarkably improved during the recompression therapy, while the other improved to
      a certain extent after additional repetitive TT6. Mild impairment of lung
      function, probably due to pulmonary oxygen toxicity, was observed on lung
      function testing in one case. In all cases, after additional TT6 and/or
      rehabilitation, patients were able to return to active daily living.

PMID- 10206934
TI  - A bloodborne pathogen program in civilian aircraft accident investigation.
AB  - The Occupational Safety and Health Administration (OSHA) amended 29 CFR Part 1910
      in 1991 to include regulations addressing occupational exposure to bloodborne
      pathogens (BBP). The rule affects all employees that have the potential for
      occupational exposure to these pathogens. The National Transportation Safety
      Board (NTSB) and Federal Aviation Administration (FAA) are the primary
      organizations involved in aircraft accident investigation in the United States.
      No other organizations in this country have a similar scope or mandate of
      responsibility. An accident scene presents significant challenges in terms of
      implementing a program which was primarily envisioned to affect personnel in
      "traditional" healthcare delivery facilities; the OSHA requirements now had to be
      met in the chaotic, inhospitable, and logistically difficult environment of an
      aircraft accident site. Unanticipated issues such as heat-related conditions,
      performance of physically demanding work in cumbersome gear, biohazard trash
      disposal from remote sites, and a host of other problems had to be dealt with.
      The FAA, in close cooperation with other Federal agencies, developed a training
      and administrative program to meet the requirements of the OSHA BBP rule as it
      relates to the unique environment of an aircraft accident site. The program has
      been implemented and successfully tested under actual field conditions at several
      major aviation accidents that have occurred recently. This article provides
      observations on the FAA's program and lessons learned from its implementation.

PMID- 10206935
TI  - Space medicine: what lies ahead?

PMID- 10206936
TI  - Medical support for the International Space Station.

PMID- 10206937
TI  - Medical issues for a mission to Mars.

PMID- 10206938
TI  - Biomedical investigations conducted in support of the Extended Duration Orbiter
      Medical Project.

PMID- 10206939
TI  - Surgical care in space.

PMID- 10206940
TI  - Internet and World Wide Web technologies for medical data management and remote
      access to clinical expertise.

PMID- 10206941
TI  - You're the flight surgeon. Panic disorder.

PMID- 10206942
TI  - Evoked potentials and decompression.

PMID- 10206943
TI  - Homeopathic remedies for jet lag.

PMID- 10206944
TI  - Cervical pain in aviators.

PMID- 10206945
TI  - Mammalian diacylglycerol kinases, a family of lipid kinases with signaling
      functions.

PMID- 10206946
TI  - How does arrestin respond to the phosphorylated state of rhodopsin?
AB  - Visual arrestin quenches light-induced signaling by binding to light-activated,
      phosphorylated rhodopsin (P-Rh*). Here we present structure-function data, which
      in conjunction with the refined crystal structure of arrestin (Hirsch, J. A.,
      Schubert, C., Gurevich, V. V., and Sigler, P. B. (1999) Cell, in press), support
      a model for the conversion of a basal or "inactive" conformation of free arrestin
      to one that can bind to and inhibit the light activated receptor. The trigger for
      this transition is an interaction of the phosphorylated COOH-terminal segment of
      the receptor with arrestin that disrupts intramolecular interactions, including a
      hydrogen-bonded network of buried, charged side chains, referred to as the "polar
      core." This disruption permits structural adjustments that allow arrestin to bind
      to the receptor. Our mutational survey identifies residues in arrestin (Arg175,
      Asp30, Asp296, Asp303, Arg382), which when altered bypass the need for the
      interaction with the receptor's phosphopeptide, enabling arrestin to bind to
      activated, nonphosphorylated rhodopsin (Rh*). These mutational changes disrupt
      interactions and substructures which the crystallographic model and previous
      biochemical studies have shown are responsible for maintaining the inactive
      state. The molecular basis for these disruptions was confirmed by successfully
      introducing structure-based second site substitutions that restored the critical
      interactions. The nearly absolute conservation of the mutagenically sensitive
      residues throughout the arrestin family suggests that this mechanism is likely to
      be applicable to arrestin-mediated desensitization of most G-protein-coupled
      receptors.

PMID- 10206948
TI  - Increased expression of Rab5a correlates directly with accelerated maturation of
      Listeria monocytogenes phagosomes.
AB  - Previous studies have shown that Listeria monocytogenes (LM) modulates phagocytic
      membrane traffic. Here we explore whether Rab5a, a GTPase associated with
      phagosome-endosome fusion, is related to phagosome maturation and to the
      intracellular survival of LM. Stable transfection of Rab5a cDNA into macrophages
      accelerates intracellular degradation of LM. Morphological studies confirmed that
      phagosome maturation and phagosome-lysosome fusion is enhanced by overexpression
      of Rab5a. Down-regulation experiments using antisense oligonucleotides targeted
      to the Rab5a mRNA efficiently reduced Rab5a synthesis, reduced phagosome-endosome
      traffic, blocked phagosome-lysosome fusion, and extended intraphagosomal survival
      of LM. Down-regulation of Rab5a had no effect on LM internalization. Down
      regulation of Rab5c had no effect on phagosome maturation and phagosome-lysosome
      fusion. The results indicate that Rab5a controls early phagosome-endosome
      interactions and governs the maturation of the early phagosome leading to
      phagosome-lysosome fusion.

PMID- 10206947
TI  - Cloning and expression of a plasma membrane cystine/glutamate exchange
      transporter composed of two distinct proteins.
AB  - Transport system xc- found in plasma membrane of cultured mammalian cells is an
      exchange agency for anionic amino acids with high specificity for anionic form of
      cystine and glutamate. We have isolated cDNA encoding the transporter for system
      xc- from mouse activated macrophages by expression in Xenopus oocytes. The
      expression of system xc- activity in oocytes required two cDNA transcripts, and
      the sequence analysis revealed that one is identical with the heavy chain of 4F2
      cell surface antigen (4F2hc) and the other is a novel protein of 502 amino acids
      with 12 putative transmembrane domains. The latter protein, named xCT, showed a
      significant homology with those recently reported to mediate cationic or
      zwitterionic amino acid transport when co-expressed with 4F2hc. Thus xCT is a new
      member of a family of amino acid transporters that form heteromultimeric complex
      with 4F2hc, with a striking difference in substrate specificity. The expression
      of system xc- was highly regulated, and Northern blot analysis demonstrated that
      the expression of both 4F2hc and xCT was enhanced in macrophages stimulated by
      lipopolysaccharide or an electrophilic agent. However, the expression of xCT was
      more directly correlated with the system xc- activity.

PMID- 10206949
TI  - Interaction of SeqA and Dam methylase on the hemimethylated origin of Escherichia
      coli chromosomal DNA replication.
AB  - Preferential binding of SeqA protein to hemimethylated oriC, the origin of
      Escherichia coli chromosomal replication, delays methylation by Dam methylase.
      Because the SeqA-oriC interaction appears to be essential in timing of
      chromosomal replication initiation, the biochemical functions of SeqA protein and
      Dam methylase at the 13-mer L, M, and R region containing 4 GATC sequences at the
      left end of oriC were examined. We found that SeqA protein preferentially bound
      hemimethylated 13-mers but not fully nor unmethylated 13-mers. Regardless of
      strand methylation, the binding of SeqA protein to the hemimethylated GATC
      sequence of 13-mer L was followed by additional binding to other hemimethylated
      GATC sequences of 13-mer M and R. On the other hand, Dam methylase did not
      discriminate binding of 13-mers in different methylation patterns and was not
      specific to GATC sequences. The binding specificity and higher affinity of SeqA
      protein over Dam methylase to the hemimethylated 13-mers along with the reported
      cellular abundance of this protein explains the dominant action of SeqA protein
      over Dam methylase to the newly replicated oriC for the sequestration of
      chromosomal replication. Furthermore, SeqA protein bound to hemimethylated 13
      mers was not dissociated by Dam methylase, and most SeqA protein spontaneously
      dissociated 10 min after binding. Also, SeqA protein delayed the in vitro
      methylation of hemimethylated 13-mers by Dam methylase. These in vitro results
      suggest that the intrinsic binding instability of SeqA protein results in release
      of sequestrated hemimethylated oriC.

PMID- 10206950
TI  - Identification and characterization of receptor for mammalian hepatopoietin that
      is homologous to yeast ERV1.
AB  - Hepatopoietin (HPO) is a novel polypeptide mitogen specific for hepatocytes and
      hepatoma cell lines, which is derived from liver and supports its regeneration.
      To determine whether HPO acts via a receptor-based signal transduction,
      recombinant human hepatopoietin was labeled by iodination and used to
      characterize its binding activity by specific displacement test and Scatchard
      analysis in primarily cultured rat hepatocytes and human hepatoma Hep-G2 cells.
      The binding was saturable and specific because it was replaceable by HPO but not
      by epidermal growth factor, transforming growth factor-alpha, or insulin.
      Scatchard analysis indicated the presence of a single class of high affinity
      receptor with dissociation constant (Kd) of 2 and 0.7 pM, and a receptor density
      of about 10, 000 sites/cell and 55,000 sites/cell in the rat hepatocytes and
      human hepatoma cells, respectively. The Kd values were consistent with the half
      maximum dose of HPO activity. Affinity cross-linking of the receptor with 125I
      HPO revealed a polypeptide of molecular mass approximately 90 kDa by SDS
      polyacrylamide gel electrophoresis. Thus, the molecular mass of the HPO receptor
      was calculated to be about 75 kDa. These data demonstrated the existence of an
      HPO receptor in hepatocytes and hepatoma cells, which may account for biological
      effect.

PMID- 10206951
TI  - Full peptide synthesis, purification, and characterization of six Tat variants.
      Differences observed between HIV-1 isolates from Africa and other continents.
AB  - AIDS in Africa is characterized by the equal distribution of mortality between
      the two genders because of highly virulent human immunodeficiency virus type 1
      (HIV-1) strains. The viral protein Tat trans-activates viral gene expression and
      is essential for HIV-1 replication. We chemically synthesized six different Tat
      proteins, with sizes ranging from 86 to 101 residues, from HIV-1 isolates located
      in different parts of the world including highly virulent African strains.
      Protein purification, mass spectroscopy, and amino acid analysis showed that the
      synthesis was successful in each case but with different yields. We show that all
      have the ability to bind the HIV long terminal repeat (LTR) RNA trans-activation
      response element (TAR) region, involved in Tat-mediated trans-activation, but
      structural heterogeneities are revealed by circular dichroism. These Tat
      synthetic proteins cross membranes but differ in their ability to trans-activate
      an HIV LTR-reporter gene in stably transfected HeLa cells. Two Tat proteins from
      virulent African HIV-1 strains were much more active than those from Europe and
      the United States. The interferon-induced kinase (PKR), involved in cell
      antiviral defense, phosphorylates only Tat variants corresponding to less or
      nonvirulent HIV-1 isolates. Our results indicate that the high virulence of some
      African HIV-1 strains could be related to Tat activity.

PMID- 10206952
TI  - Molecular cloning of a novel alpha2,3-sialyltransferase (ST3Gal VI) that
      sialylates type II lactosamine structures on glycoproteins and glycolipids.
AB  - A novel member of the human CMP-NeuAc:beta-galactoside alpha2, 3
      sialyltransferase (ST) subfamily, designated ST3Gal VI, was identified based on
      BLAST analysis of expressed sequence tags, and a cDNA clone was isolated from a
      human melanoma line library. The sequence of ST3Gal VI encoded a type II membrane
      protein with 2 amino acids of cytoplasmic domain, 32 amino acids of transmembrane
      region, and a large catalytic domain with 297 amino acids; and showed homology to
      previously cloned ST3Gal III, ST3Gal IV, and ST3Gal V at 34, 38, and 33%,
      respectively. Extracts from L cells transfected with ST3Gal VI cDNA in a
      expression vector and a fusion protein with protein A showed an enzyme activity
      of alpha2, 3-sialyltransferase toward Galbeta1,4GlcNAc structure on glycoproteins
      and glycolipids. In contrast to ST3Gal III and ST3Gal IV, this enzyme exhibited
      restricted substrate specificity, i.e. it utilized Galbeta1,4GlcNAc on
      glycoproteins, and neolactotetraosylceramide and neolactohexaosylceramide, but
      not lactotetraosylceramide, lactosylceramide, or asialo-GM1. Consequently, these
      data indicated that this enzyme is involved in the synthesis of sialyl
      paragloboside, a precursor of sialyl-Lewis X determinant.

PMID- 10206953
TI  - Ile-177 and Ser-180 in the S1 segment are critically important in Kv1.1 channel
      function.
AB  - Ile-177 and Ser-180 are conserved residues in the first transmembrane segment
      (S1) of the Shaker, Shab, Shaw, and Shal subfamilies of voltage-gated K+
      channels. Here we report that the mutation of these residues in Kv1.1 to leucine,
      proline, or arginine abolished the expression of outward potassium currents in
      Xenopus oocytes. Co-injection of these mutant cRNAs and wild type Kv1.1 cRNA into
      Xenopus oocytes exerted a potent dominant negative effect resulting in the
      suppression of Kv1.1-encoded currents. Transient transfection experiments of COS
      7 cells revealed that the S1 mutants directed the synthesis of Kv1.1
      polypeptides. Quantitative co-immunoprecipitation assays revealed that most of
      the S1 mutants co-assembled and formed both homo- and heteromultimeric complexes.
      Furthermore, the mutated polypeptides could reach the plasma membranes of
      transfected Sol8 cells. We conclude that mutations of Ile-177 and Ser-180 do not
      interfere with either the assembly of multimeric channel complexes or the
      targeting of these complexes to the plasma membrane. It is likely that these
      residues are involved in helix-helix interactions that are critical to the proper
      functioning of voltage-gated potassium channels.

PMID- 10206954
TI  - Mechanisms by which elevated intracellular calcium induces S49 cell membranes to
      become susceptible to the action of secretory phospholipase A2.
AB  - Exposure of S49 lymphoma cells to exogenous group IIA or V secretory
      phospholipase A2 (sPLA2) caused an initial release of fatty acid followed by
      resistance to further hydrolysis by the enzyme. This refractoriness was overcome
      by exposing cells to palmitoyl lysolecithin. This effect was specific in terms of
      lysophospholipid structure. Induction of membrane susceptibility by lysolecithin
      involved an increase in cytosolic calcium and was duplicated by incubating the
      cells with calcium ionophores such as ionomycin. Lysolecithin also activated
      cytosolic phospholipase A2 (cPLA2). Inhibition of this enzyme attenuated the
      ability of lysolecithin (but not ionomycin) to induce susceptibility to sPLA2.
      Lysolecithin or ionomycin caused concurrent hydrolysis of both
      phosphatidylethanolamine and phosphatidylcholine implying that transbilayer
      movement of phosphatidylethanolamine occurred upon exposure to these agents but
      that susceptibility is not simply due to exposure of a preferred substrate (i.e.
      phosphatidylethanolamine) to the enzyme. Microvesicles were apparently released
      from the cells upon addition of lysolecithin or ionomycin. Both these vesicles
      and the remnant cell membranes were susceptible to sPLA2. Together these data
      suggest that lysolecithin induces susceptibility through both cPLA2-dependent and
      -independent pathways. Whereas elevated cytosolic calcium was required for both
      pathways, it was sufficient only for the cPLA2-independent pathway. This cPLA2
      independent pathway involved changes in cell membrane structure associated with
      transbilayer phospholipid migration and microvesicle release.

PMID- 10206955
TI  - The myeloid-specific sialic acid-binding receptor, CD33, associates with the
      protein-tyrosine phosphatases, SHP-1 and SHP-2.
AB  - The myeloid restricted membrane glycoprotein, CD33, is a member of the recently
      characterized "sialic acid-binding immunoglobulin-related lectin" family.
      Although CD33 can mediate sialic acid-dependent cell interactions as a
      recombinant protein, its function in myeloid cells has yet to be determined.
      Since CD33 contains two potential immunoreceptor tyrosine-based inhibition motifs
      in its cytoplasmic tail, we investigated whether it might act as a signaling
      receptor in myeloid cells. Tyrosine phosphorylation of CD33 in myeloid cell lines
      was stimulated by cell surface cross-linking or by pervanadate, and inhibited by
      PP2, a specific inhibitor of Src family tyrosine kinases. Phosphorylated CD33
      recruited both the protein-tyrosine phosphatases, SHP-1 and SHP-2. CD33 was
      dephosphorylated in vitro by the co-immunoprecipitated tyrosine phosphatases,
      suggesting that it might also be an in vivo substrate. The first CD33
      phosphotyrosine motif is dominant in CD33-SHP-1/SHP-2 interactions, since
      mutating tyrosine 340 in a CD33-cytoplasmic tail fusion protein significantly
      reduced binding to SHP-1 and SHP-2 in THP-1 lysates, while mutation of tyrosine
      358 had no effect. Furthermore, the NH2-terminal Src homology 2 domain of SHP-1
      and SHP-2, believed to be essential for phosphatase activation, selectively bound
      a CD33 phosphopeptide containing tyrosine 340 but not one containing tyrosine
      358. Finally, mutation of tyrosine 340 increased red blood cell binding by CD33
      expressed in COS cells. Hence, CD33 signaling through selective recruitment of
      SHP-1/SHP-2 may modulate its ligand(s) binding activity.

PMID- 10206956
TI  - The role of an iron-sulfur cluster in an enzymatic methylation reaction.
      Methylation of CO dehydrogenase/acetyl-CoA synthase by the methylated corrinoid
      iron-sulfur protein.
AB  - This paper focuses on how a methyl group is transferred from a methyl-cobalt(III)
      species on one protein (the corrinoid iron-sulfur protein (CFeSP)) to a nickel
      iron-sulfur cluster on another protein (carbon monoxide dehydrogenase/acetyl-CoA
      synthase). This is an essential step in the Wood-Ljungdahl pathway of anaerobic
      CO and CO2 fixation. The results described here strongly indicate that transfer
      of methyl group to carbon monoxide dehydrogenase/acetyl-CoA synthase occurs by an
      SN2 pathway. They also provide convincing evidence that oxidative inactivation of
      Co(I) competes with methylation. Under the conditions of our anaerobic assay,
      Co(I) escapes from the catalytic cycle one in every 100 turnover cycles.
      Reductive activation of the CFeSP is required to regenerate Co(I) and recruit the
      protein back into the catalytic cycle. Our results strongly indicate that the
      [4Fe-4S] cluster of the CFeSP is required for reductive activation. They support
      the hypothesis that the [4Fe-4S] cluster of the CFeSP does not participate
      directly in the methyl transfer step but provides a conduit for electron flow
      from physiological reductants to the cobalt center.

PMID- 10206957
TI  - The catalytic mechanism of endoplasmic reticulum signal peptidase appears to be
      distinct from most eubacterial signal peptidases.
AB  - Many type I signal peptidases from eubacterial cells appear to contain a
      serine/lysine catalytic dyad. In contrast, our data show that the signal
      peptidase complex from the endoplasmic reticulum lacks an apparent catalytic
      lysine. Instead, a serine, histidine, and two aspartic acids are important for
      signal peptidase activity by the Sec11p subunit of the yeast signal peptidase
      complex. Amino acids critical to the eubacterial signal peptidases and Sec11p
      are, however, positioned similarly along their primary sequences, suggesting the
      presence of a common structural element(s) near the catalytic sites of these
      enzymes.

PMID- 10206958
TI  - Initially transcribed sequences strongly affect the extent of abortive initiation
      by RNA polymerase II.
AB  - We investigated transcript initiation and early elongation by RNA polymerase II
      using templates mismatched between -9 and +3 (bubble templates). Highly purified
      RNA polymerase II alone was able to initiate transcription specifically on these
      templates in the presence of dinucleotide primers. The length distribution of
      abortively initiated RNAs was similar for purified RNA polymerase II on bubble
      templates and polymerase II on double-stranded templates in HeLa nuclear
      extracts. Increasing the U content in the initial portion of the transcript
      caused similar increases in abortive initiation for transcription of bubble
      templates by pure polymerase and double-stranded templates in extracts. Thus, the
      level of abortive initiation by RNA polymerase II is at least partly determined
      by interactions of the polymerase with the transcript and/or the template,
      independent of the general transcription factors. Substitution of 5-bromo-UTP for
      UTP reduced abortive initiation on bubble templates, consistent with the idea
      that transcription complex stability during early elongation depends on the
      strength of the initial RNA-DNA hybrid. Interestingly, transcription of bubble
      templates in HeLa extracts gave very high levels of abortive initiation,
      suggesting that inability to reanneal the initially melted template segment
      inhibits transcript elongation in the presence of the initiation factors.

PMID- 10206959
TI  - p53 down-regulates human matrix metalloproteinase-1 (Collagenase-1) gene
      expression.
AB  - Recent studies show that the p53 tumor suppressor protein is overexpressed in
      rheumatoid arthritis (RA) synovium and that somatic mutations previously
      identified in human tumors are present in RA synovium (Firestein, G. S.,
      Echeverri, F., Yeo, M., Zvaifler, N. J., and Green, D. R. (1997) Proc. Natl.
      Acad. Sci. U. S. A. 94, 10895-10900; Firestein, G. S., Nguyen, K., Aupperle, K.
      R., Yeo, M., Boyle, D. L., and Zvaifler, N. J. (1996) Am. J. Pathol. 149, 2143
      2151; Reme, T., Travaglio, A., Gueydon, E., Adla, L., Jorgensen, C., and Sany, J.
      (1998) Clin. Exp. Immunol. 111, 353-3581). We hypothesize that the abnormality of
      p53 seen in RA synovium may contribute to joint degeneration through the
      regulation of human matrix metalloproteinase-1 (hMMP-1, collagenase-1) gene
      expression. Transcription assays were performed with luciferase reporters driven
      by the promoter of the hMMP-1 gene or by a minimal promoter containing tandem
      repeats of the consensus binding sequence for activator protein-1, cotransfected
      with p53-expressing plasmids. The results revealed that (i) wild-type (wt) p53
      down-regulated the promoter activity of hMMP-1 in a dose-dependent fashion; (ii)
      four of six p53 mutants (commonly found in human cancers) lost this repression
      activity; and (iii) this p53 repression activity was mediated at least in part by
      the activator protein-1 sites found in the hMMP-1 promoter. These findings were
      further confirmed by Northern analysis. The down-regulation of hMMP-1 gene
      expression by endogenous wt-p53 was shown by treatment of U2-OS cells, a wt-p53
      containing osteogenic sarcoma line, and Saos-2 cells, a p53-negative osteogenic
      sarcoma line, with etoposide, a potent inducer of p53 expression. p53, activated
      by etoposide, appears to block hMMP-1 promoter activity induced by etoposide in
      U2-OS cells. In summary, we have shown for the first time that the hMMP-1 gene is
      a p53 target gene, subject to p53 repression. Because MMP-1 is principally
      responsible for the irreversible destruction of collagen in articular tissue in
      RA, abnormality of p53 may contribute to joint degeneration through the
      regulation of MMP-1 expression.

PMID- 10206960
TI  - Targeted correction of an episomal gene in mammalian cells by a short DNA
      fragment tethered to a triplex-forming oligonucleotide.
AB  - Triplex-forming oligonucleotides (TFOs) can bind to polypurine/polypyrimidine
      regions in DNA in a sequence-specific manner and provoke DNA repair. We have
      coupled a TFO to a short donor fragment of DNA that shares homology to a selected
      gene as a strategy to mediate gene targeting and correction. In this bifunctional
      oligonucleotide, the TFO domain is designed to bind the target gene and stimulate
      repair and recombination, with the donor domain positioned for recombination and
      information transfer. A series of these tethered donor-TFO (TD-TFO) molecules
      with donor domains of 40-44 nucleotides and TFO domains in both the purine and
      pyrimidine triplex motifs were tested for their ability to mediate either gene
      correction or mutation of a supF reporter gene contained in a SV40 shuttle vector
      in mammalian cells. In vitro binding assays revealed that the attachment of the
      donor domain via a flexible linker did not significantly alter the binding
      affinity of the TFO domain for the polypurine site in the supF target DNA, with
      equilibrium dissociation constants in the 10(-8) M range. Experiments in which
      the target vector and the linked TD-TFOs were pre-incubated in vitro and co
      transfected into cells led to conversion frequencies approaching 1%, 4-fold
      greater than with the two domains unlinked. When cells that had been previously
      transfected with the SV40 vector were electroporated with the TD-TFOs,
      frequencies of base pair-specific gene correction were seen in the range of
      0.04%, up to 50-fold over background and at least 3-fold over either domain alone
      or in unlinked combinations. Sequence conversion by the TD-TFOs was achieved
      using either single- or double-stranded donor domains and either triplex motif.
      Substitution of either domain in the TD-TFO with control sequences yielded
      reagents with diminished activity, as did mixtures of unlinked TFO and donor DNA
      segments. The boost in activity provided by the attached TFO domain was reduced
      in cells deficient in the nucleotide excision repair factor XPA but was restored
      in a subclone of these cells expressing XPA cDNA, suggesting a role for
      nucleotide excision repair in the pathway of triple helix-stimulated gene
      conversion. The ability to correct or mutate a specific target site in mammalian
      cells using the TD-TFO strategy may provide a useful tool for research and
      possibly for therapeutic applications.

PMID- 10206961
TI  - An APAF-1.cytochrome c multimeric complex is a functional apoptosome that
      activates procaspase-9.
AB  - We report here the reconstitution of the de novo procaspase-9 activation pathway
      using highly purified cytochrome c, recombinant APAF-1, and recombinant
      procaspase-9. APAF-1 binds and hydrolyzes ATP or dATP to ADP or dADP,
      respectively. The hydrolysis of ATP/dATP and the binding of cytochrome c promote
      APAF-1 oligomerization, forming a large multimeric APAF-1.cytochrome c complex.
      Such a complex can be isolated using gel filtration chromatography and is by
      itself sufficient to recruit and activate procaspase-9. The stoichiometric ratio
      of procaspase-9 to APAF-1 is approximately 1 to 1 in the complex. Once activated,
      caspase-9 disassociates from the complex and becomes available to cleave and
      activate downstream caspases such as caspase-3.

PMID- 10206962
TI  - Dibromopropanone cross-linking of the phosphopantetheine and active-site cysteine
      thiols of the animal fatty acid synthase can occur both inter- and intrasubunit.
      Reevaluation of the side-by-side, antiparallel subunit model.
AB  - The objective of this study was to test a new model for the homodimeric animal
      FAS which implies that the condensation reaction can be catalyzed by the amino
      terminal beta-ketoacyl synthase domain in cooperation with the penultimate
      carboxyl-terminal acyl carrier protein domain of either subunit. Treatment of
      animal fatty acid synthase dimers with dibromopropanone generates three new
      molecular species with decreased electrophoretic mobilities; none of these
      species are formed by fatty acid synthase mutant dimers lacking either the active
      site cysteine of the beta-ketoacyl synthase domain (C161A) or the
      phosphopantetheine thiol of the acyl carrier protein domain (S2151A). A double
      affinity-labeling strategy was used to isolate dimers that carried one or both
      mutations on one or both subunits; the heterodimers were treated with
      dibromopropanone and analyzed by a combination of sodium dodecyl
      sulfate/polyacrylamide gel electrophoresis, Western blotting, gel filtration, and
      matrix-assisted laser desorption mass spectrometry. Thus the two slowest moving
      of these species, which accounted for 45 and 15% of the total, were identified as
      doubly and singly cross-linked dimers, respectively, whereas the fastest moving
      species, which accounted for 35% of the total, was identified as originating from
      internally cross-linked subunits. These results show that the two polypeptides of
      the fatty acid synthase are oriented such that head-to-tail contacts are formed
      both between and within subunits, and provide the first structural evidence in
      support of the new model.

PMID- 10206963
TI  - Overexpression of human apolipoprotein A-II in mice induces hypertriglyceridemia
      due to defective very low density lipoprotein hydrolysis.
AB  - Two lines of transgenic mice, hAIItg-delta and hAIItg-lambda, expressing human
      apolipoprotein (apo)A-II at 2 and 4 times the normal concentration, respectively,
      displayed on standard chow postprandial chylomicronemia, large quantities of very
      low density lipoprotein (VLDL) and low density lipoprotein (LDL) but greatly
      reduced high density lipoprotein (HDL). Hypertriglyceridemia may result from
      increased VLDL production, decreased VLDL catabolism, or both. Post-Triton VLDL
      production was comparable in transgenic and control mice. Postheparin lipoprotein
      lipase (LPL) and hepatic lipase activities decreased at most by 30% in transgenic
      mice, whereas adipose tissue and muscle LPL activities were unaffected,
      indicating normal LPL synthesis. However, VLDL-triglyceride hydrolysis by
      exogenous LPL was considerably slower in transgenic compared with control mice,
      with the apparent Vmax of the reaction decreasing proportionately to human apoA
      II expression. Human apoA-II was present in appreciable amounts in the VLDL of
      transgenic mice, which also carried apoC-II. The addition of purified apoA-II in
      postheparin plasma from control mice induced a dose-dependent decrease in LPL and
      hepatic lipase activities. In conclusion, overexpression of human apoA-II in
      transgenic mice induced the proatherogenic lipoprotein profile of low plasma HDL
      and postprandial hypertriglyceridemia because of decreased VLDL catabolism by
      LPL.

PMID- 10206964
TI  - The bombesin receptor subtypes have distinct G protein specificities.
AB  - We used an in situ reconstitution assay to examine the receptor coupling to
      purified G protein alpha subunits by the bombesin receptor family, including
      gastrin-releasing peptide receptor (GRP-R), neuromedin B receptor (NMB-R), and
      bombesin receptor subtype 3 (BRS-3). Cells expressing GRP-R or NMB-R catalyzed
      the activation of squid retinal Galphaq and mouse Galphaq but not bovine retinal
      Galphat or bovine brain Galphai/o. The GRP-R- and NMB-R-catalyzed activations of
      Galphaq were dependent upon and enhanced by different betagamma dimers in the
      same rank order as follows: bovine brain betagamma > beta1gamma2 >> beta1gamma1.
      Despite these qualitative similarities, GRP-R and NMB-R had distinct kinetic
      properties in receptor-G protein coupling. GRP-R had higher affinities for bovine
      brain betagamma, beta1gamma1, and beta1gamma2 and squid retinal Galphaq. In
      addition, GRP-R showed higher catalytic activity on squid Galphaq. Like GRP-R and
      NMB-R, BRS-3 did not catalyze GTPgammaS binding to Galphai/o or Galphat. However,
      BRS-3 showed little, if any, coupling with squid Galphaq but clearly activated
      mouse Galphaq. GRP-R and NMB-R catalyzed GTPgammaS binding to both squid and
      mouse Galphaq, with GRP-R activating squid Galphaq more effectively, and NMB-R
      also showed slight preference for squid Galphaq. These studies reveal that the
      structurally similar bombesin receptor subtypes, in particular BRS-3, possess
      distinct coupling preferences among members of the Galphaq family.

PMID- 10206965
TI  - Glu300 of rat carboxypeptidase E is essential for enzymatic activity but not
      substrate binding or routing to the regulated secretory pathway.
AB  - Several recently discovered members of the carboxypeptidase E (CPE) gene family
      lack critical active site residues that are conserved in other family members.
      For example, three CPE-like proteins contain a Tyr in place of Glu300 (equivalent
      to Glu270 of carboxypeptidase A and B). To investigate the importance of this
      position, Glu300 of rat CPE was converted into Gln, Lys, or Tyr, and the proteins
      expressed in Sf9 cells using the baculovirus system. All three mutants were
      secreted from the cells, but the media showed no enzyme activity above background
      levels. Wild-type CPE and the Gln300 point mutant bound to a p-aminobenzoyl-Arg
      Sepharose affinity resin, and this binding was competed by an active site
      directed inhibitor, guanidinoethylmercaptosuccinic acid. The affinity purified
      mutant CPE protein showed no detectable enzyme activity (<0.004% of wild-type
      CPE) toward dansyl-Phe-Ala-Arg. Expression of the Gln300 and Lys300 mutant CPE
      proteins in the NIT3 mouse pancreatic beta-cell line showed that these mutants
      are routed into secretory vesicles and secreted via the regulated pathway. Taken
      together, these results indicate that Glu300 of CPE is essential for enzyme
      activity, but not required for substrate binding or for routing into the
      regulated secretory pathway.

PMID- 10206966
TI  - Two regions of sulfonylurea receptor specify the spontaneous bursting and ATP
      inhibition of KATP channel isoforms.
AB  - KATP channels are heteromultimers of KIR6.2 and a sulfonylurea receptor, SUR, an
      ATP binding cassette (ABC) protein with several isoforms. KIR6.2 forms a channel
      pore whose spontaneous activity and ATP sensitivity are modulated by the receptor
      via an unknown interaction(s). Side by side comparison of single-channel kinetics
      and steady-state ATP inhibition of human beta-cell, SUR1/KIR6.2, versus cardiac,
      SUR2A/KIR6.2 channels demonstrate that the latter have a greater mean burst
      duration and open probability in the absence of nucleotides and approximately 4
      fold higher IC50(ATP). We have used matched chimeras of SUR1 and SUR2A to show
      that the kinetics, which determine the maximal open probability (Pomax), and the
      ATP sensitivity are functionally separable and to identify the two segments of
      SUR responsible for these isoform differences. A region within the first five
      transmembrane domains specifies the interburst kinetics, whereas a C-terminal
      segment determines the sensitivity to inhibitory ATP. The separable effects of
      SUR on ATP inhibition and channel kinetics implies that the cytoplasmic C
      terminus of SUR either directly modulates the affinity of a weak ATP binding site
      on the inward rectifier or affects linkage between the binding site and the gate.
      This is the first identification of parts of an ABC protein that interact with an
      ion channel subunit to modulate the spontaneous activity and ATP sensitivity of
      the heteromeric channel.

PMID- 10206967
TI  - Membrane dipeptidase is the receptor for a lung-targeting peptide identified by
      in vivo phage display.
AB  - In vivo phage display is a powerful method to study organ- and tissue-specific
      vascular addresses. Using this approach, peptides capable of tissue-specific
      homing can be identified by performing a selection for that trait in vivo. We
      recently showed that the CGFECVRQCPERC (termed GFE-1) peptide can selectively
      bind to mouse lung vasculature after an intravenous injection. Our aim in the
      present study was to identify the receptor for this lung-homing peptide. By using
      affinity chromatography, we isolated a 55-kDa lung cell-surface protein that
      selectively binds to the GFE-1 peptide. Protein sequencing established the
      identity of the receptor as membrane dipeptidase (MDP), a cell-surface zinc
      metalloprotease involved in the metabolism of glutathione, leukotriene D4, and
      certain beta-lactam antibiotics. Phage particles displaying the GFE-1 peptide
      selectively bind to COS-1 cells transfected with the murine MDP cDNA. Moreover,
      the synthetic GFE-1 peptide could inhibit MDP activity. By establishing MDP as
      the receptor for the GFE-1 peptide, our results suggest potential applications
      for both MDP and the GFE-1 peptide in delivery of compounds to the lungs. This
      work also demonstrates that cell-surface proteases can be involved in tissue
      specific homing.

PMID- 10206968
TI  - Distinct molecular bases for pH sensitivity of the guard cell K+ channels KST1
      and KAT1.
AB  - Acid-induced potassium uptake through K+ channels is a prerequisite for stomatal
      opening. Our previous studies identified a pore histidine as a major component of
      the acid activation mechanism of the potato guard cell K+ channel KST1 (1).
      Although this histidine is highly conserved among all plant K+ uptake channels
      cloned so far, the pH-dependent gating of the Arabidopsis thaliana guard cell K+
      channel KAT1 was not affected by mutations of this histidine. In both channels,
      KST1 and KAT1, aspartate mutants in the K+ channel consensus sequence GYGD
      adjacent to the histidine (KST1-D269N and KAT1-D265N) were inhibited by a rise in
      the extracellular proton concentration. pH changes affected the half-maximal
      activation voltage V(1)/(2) of the KST1 mutant, whereas in the mutant channel
      KAT1-D265N an acid-induced decrease in the maximum conductance gmax indicated the
      presence of a proton block. In contrast to the wild type KST1, the S4-mutant
      channel KST1-R181Q exhibited an activation upon alcalization of the extracellular
      solution. From our electrophysiological studies on channel mutants with respect
      to the pore histidine as well as the aspartate, we conclude that the common
      proton-supported shift in the voltage dependence of KST1 and KAT1 is based on
      distinct molecular elements.

PMID- 10206969
TI  - The beta-subunits of Na+,K+-ATPase and gastric H+,K+-ATPase have a high
      preference for their own alpha-subunit and affect the K+ affinity of these
      enzymes.
AB  - The alpha- and beta-subunits of Na+,K+-ATPase and H+,K+-ATPase were expressed in
      Sf9 cells in different combinations. Immunoprecipitation of the alpha-subunits
      resulted in coprecipitation of the accompanying beta-subunit independent of the
      type of beta-subunit. This indicates cross-assembly of the subunits of the
      different ATPases. The hybrid ATPase with the catalytic subunit of Na+,K+-ATPase
      and the beta-subunit of H+,K+-ATPase (NaKalphaHKbeta) showed an ATPase activity,
      which was only 12 +/- 4% of the activity of the Na+,K+-ATPase with its own beta
      subunit. Likewise, the complementary hybrid ATPase with the catalytic subunit of
      H+,K+-ATPase and the beta-subunit of Na+,K+-ATPase (HKalphaNaKbeta) showed an
      ATPase activity which was 9 +/- 2% of that of the recombinant H+,K+-ATPase. In
      addition, the apparent K+ affinity of hybrid NaKalphaHKbeta was decreased, while
      the apparent K+ affinity of the opposite hybrid HKalphaNaKbeta was increased. The
      hybrid NaKalphaHKbeta could be phosphorylated by ATP to a level of 21 +/- 7% of
      that of Na+,K+-ATPase. These values, together with the ATPase activity gave
      turnover numbers for NaKalphabeta and NaKalphaHKbeta of 8800 +/- 310 min-1 and
      4800 +/- 160 min-1, respectively. Measurements of phosphorylation of the
      HKalphaNaKbeta and HKalphabeta enzymes are consistent with a higher turnover of
      the former. These findings suggest a role of the beta-subunit in the catalytic
      turnover. In conclusion, although both Na+,K+-ATPase and H+,K+-ATPase have a high
      preference for their own beta-subunit, they can function with the beta-subunit of
      the other enzyme, in which case the K+ affinity and turnover number are modified.

PMID- 10206971
TI  - The reaction of the substrate analog 2-ketoglutarate with adenosylcobalamin
      dependent glutamate mutase.
AB  - Glutamate mutase is one of several adenosylcobalamin-dependent enzymes that
      catalyze unusual rearrangements that proceed through a mechanism involving free
      radical intermediates. The enzyme exhibits remarkable specificity, and so far no
      molecules other than L-glutamate and L-threo-3-methylaspartate have been found to
      be substrates. Here we describe the reaction of glutamate mutase with the
      substrate analog, 2-ketoglutarate. Binding of 2-ketoglutarate (or its hydrate) to
      the holoenzyme elicits a change in the UV-visible spectrum consistent with the
      formation of cob(II)alamin on the enzyme. 2-ketoglutarate undergoes rapid
      exchange of tritium between the 5'-position of the coenzyme and C-4 of 2
      ketoglutarate, consistent with the formation of a 2-ketoglutaryl radical
      analogous to that formed with glutamate. Under aerobic conditions this leads to
      the slow inactivation of the enzyme, presumably through reaction of free radical
      species with oxygen. Despite the formation of a substrate-like radical, no
      rearrangement of 2-ketoglutarate to 3-methyloxalacetate could be detected. The
      results indicate that formation of the C-4 radical of 2-ketoglutarate is a facile
      process but that it does not undergo further reactions, suggesting that this may
      be a useful substrate analog with which to investigate the mechanism of coenzyme
      homolysis.

PMID- 10206970
TI  - 4-Hydroxynonenal prevents NF-kappaB activation and tumor necrosis factor
      expression by inhibiting IkappaB phosphorylation and subsequent proteolysis.
AB  - Extensively oxidized low density lipoprotein (ox-LDL), a modulator of
      atherogenesis, down-regulates the lipopolysaccharide (LPS)-induced activation of
      transcription factor NF-kappaB. We investigated whether 4-hydroxynonenal (HNE), a
      prominent aldehyde component of ox-LDL, represents one of the inhibitory
      substances. NF-kappaB activation by stimuli such as LPS, interleukin (IL)-1beta,
      and phorbol ester, but not tumor necrosis factor (TNF), was reversibly inhibited
      by HNE in a dose-dependent manner in human monocytic cells, whereas AP-1 binding
      was unaffected. Using similar HNE concentrations, LPS-induced kappaB- and TNF or
      IL-8 promoter-dependent transcription was prevented. Furthermore, pretreatment
      with HNE suppressed TNF production but not lactate dehydrogenase levels. Under
      these conditions the binding of LPS to monocytic cells was not significantly
      affected. However, induced proteolysis of the inhibitory proteins IkappaB-alpha,
      IkappaB-beta, and, at a later time point, IkappaB-epsilon was prevented. This is
      not due to inhibition of the proteasome, the major proteolytic activities of
      which remain unaffected, but rather to a specific prevention of the activation
      dependent phosphorylation of IkappaB-alpha. This is the first report which
      demonstrates that HNE specifically inhibits the NF-kappaB/Rel system. Down
      modulation of NF-kappaB-regulated gene expression may contribute at certain
      stages of atherosclerosis to low levels of chronic inflammation and may also be
      involved in other inflammatory/degenerative diseases.

PMID- 10206972
TI  - Transcription termination factor Rho contains three noncatalytic nucleotide
      binding sites.
AB  - The active form of transcription termination factor rho from Escherichia coli is
      a homohexamer, but several studies suggest that the six subunits of the hexamer
      are not functionally identical. Rho has three tight and three weak ATP binding
      sites. Based on our findings, we propose that the tight nucleotide binding sites
      are noncatalytic and the weak sites are catalytic. In the presence of RNA, the
      rho-catalyzed ATPase rate is fast, close to 30 s-1. However, under these
      conditions the three tightly bound nucleotides dissociate from the rho hexamer at
      a slow rate of 0.02 s-1, indicating that the three tight nucleotide binding sites
      of rho do not participate in the fast ATPase turnover. These slowly exchanging
      nucleotide binding sites of rho are capable of hydrolyzing ATP, but the resulting
      products (ADP and Pi) bind tightly and dissociate from rho about 1500 times
      slower than the fast ATPase turnover. Both RNA and excess ATP in solution are
      necessary for stabilizing nucleotide binding at these sites. In the absence of
      RNA, or when solution ATP is hydrolyzed to ADP, a faster dissociation of
      nucleotides was observed. Based on these results, we propose that the rho hexamer
      is similar to the F1-ATPase and T7 DNA helicase-containing noncatalytic sites
      that do not participate in the fast ATPase turnover. We propose that the three
      tight sites on rho are the noncatalytic sites and the three weak sites are the
      catalytic sites.

PMID- 10206973
TI  - Dimerization of the calcium-sensing receptor occurs within the extracellular
      domain and is eliminated by Cys --> Ser mutations at Cys101 and Cys236.
AB  - Calcium-sensing receptors are present in membranes as dimers that can be reduced
      to monomers with sufhydryl reagents. All studies were carried out on the human
      calcium-sensing receptor tagged at the carboxyl terminus with green fluorescent
      protein (hCaR-GFP) to permit identification and localization of expressed
      proteins. Truncations containing either the extracellular agonist binding domain
      plus transmembrane helix 1 (ECD/TMH1-GFP) or the transmembrane domain plus the
      intracellular carboxyl terminus (TMD/carboxyl terminus-GFP) were used to identify
      the dimerization domain. ECD/TMH1-GFP was a dimer in the absence of reducing
      reagents, whereas TMD/carboxyl-terminal GFP was a monomer in the absence or
      presence of reducing agents, suggesting that dimerization occurs via the ECD. To
      identify the residue(s) involved in dimerization within the ECD, cysteine -->
      serine point mutations were made in residues that are conserved between hCaR and
      metabotropic glutamate receptors. Mutations at positions 60 and 131 were
      expressed at levels comparable to wild type in HEK 293 cells, had minimal effects
      on hCaR function, and did not eliminate dimerization, whereas mutations at
      positions 101 and 236 greatly decreased receptor expression and resulted in
      significant amounts of monomer in the absence of reducing agents. The double
      point mutant hCaR(C101S/C236S)-GFP was expressed more robustly than either C101S
      or C236S and covalent dimerization was eliminated. hCaR(C101S/C236S)-GFP had a
      decreased affinity for extracellular Ca2+ and slower response kinetics upon
      increases or decreases in agonist concentration. These results suggest that
      covalent, disulfide bond-mediated dimerization of the calcium-sensing receptor
      contributes to stabilization of the ECD and to acceleration of the transitions
      between inactive and active receptor conformations.

PMID- 10206974
TI  - Transcriptional antagonism between Hmx1 and Nkx2.5 for a shared DNA-binding site.
AB  - The recently described Hmx family of homeodomain proteins is predominately
      expressed in discrete regions of developing sensory tissues. In this report, we
      have identified the preferred DNA-binding site of the murine Hmx3 homeodomain
      protein by the selection and amplification binding (SAAB) technique. The
      consensus Hmx-binding site contained the sequence 5'-CAAGTG-3', which differs
      from the 5'-TAAT-3' motif commonly associated with homeodomain proteins. Instead,
      the Hmx consensus is similar to the 5'-CAAGTG-3'-binding sites of Nkx2.1 and
      Nkx2.5 homeodomain proteins. Based on mutation studies, both the 5'-CAAG-3' core
      and the 3'-TG dinucleotide are required for high affinity binding by Hmx3 and the
      homologous Hmx1 protein. A critical determinant of this specificity is the
      glutamine at position 50 in the third helix of the Hmx homeodomain. Hmx1 binds to
      the 5'-CAAGTG-3' element with an apparent dissociation constant of 20 nM.
      Unexpectedly, the human Hmx1 protein specifically repressed transcription from a
      luciferase reporter gene containing 3 copies of the 5'-CAAGTG-3' sequence. In
      contrast, the Nkx2.5 protein transactivated this luciferase reporter.
      Interestingly, co-expression of Hmx1 and Nkx2.5 attenuated each others activity,
      suggesting that genes containing the CAAGTG element can integrate signals from
      these proteins. Therefore, Hmx1 and Nkx2. 5 proteins bind a unique DNA sequence
      and act as transcriptional antagonists.

PMID- 10206975
TI  - Suppression of Kir2.3 activity by protein kinase C phosphorylation of the channel
      protein at threonine 53.
AB  - Kir2.3 plays an important part in the maintenance of membrane potential in
      neurons and myocardium. Identification of intracellular signaling molecules
      controlling this channel thus may lead to an understanding of the regulation of
      membrane excitability. To determine whether Kir2.3 is modulated by direct
      phosphorylation of its channel protein and identify the phosphorylation site of
      protein kinase C (PKC), we performed experiments using several recombinant and
      mutant Kir2.3 channels. Whole-cell Kir2.3 currents were inhibited by phorbol 12
      myristate 13-acetate (PMA) in Xenopus oocytes. When the N-terminal region of
      Kir2.3 was replaced with that of Kir2.1, another member in the Kir2 family that
      is insensitive to PMA, the chimerical channel lost its PMA sensitivity. However,
      substitution of the C terminus was ineffective. Four potential PKC
      phosphorylation sites in the N terminus were studied by comparing mutations of
      serine or threonine with their counterpart residues in Kir2.1. Whereas
      substitutions of serine residues at positions 5, 36, and 39 had no effect on the
      channel sensitivity to PMA, mutation of threonine 53 completely eliminated the
      channel response to PMA. Interestingly, creation of this threonine residue at the
      corresponding position (I79T) in Kir2.1 lent the mutant channel a PMA sensitivity
      almost identical to the wild-type Kir2.3. These results therefore indicate that
      Kir2.3 is directly modulated by PKC phosphorylation of its channel protein and
      threonine 53 is the PKC phosphorylation site in Kir2.3.

PMID- 10206976
TI  - Leucine regulates translation of specific mRNAs in L6 myoblasts through mTOR
      mediated changes in availability of eIF4E and phosphorylation of ribosomal
      protein S6.
AB  - Regulation of translation of mRNAs coding for specific proteins plays an
      important role in controlling cell growth, differentiation, and transformation.
      Two proteins have been implicated in the regulation of specific mRNA translation:
      eukaryotic initiation factor eIF4E and ribosomal protein S6. Increased
      phosphorylation of eIF4E as well as its overexpression are associated with
      stimulation of translation of mRNAs with highly structured 5'-untranslated
      regions. Similarly, phosphorylation of S6 results in preferential translation of
      mRNAs containing an oligopyrimidine tract at the 5'-end of the message. In the
      present study, leucine stimulated phosphorylation of the eIF4E-binding protein,
      4E-BP1, in L6 myoblasts, resulting in dissociation of eIF4E from the inactive
      eIF4E.4E-BP1 complex. The increased availability of eIF4E was associated with a
      1.6-fold elevation in ornithine decarboxylase relative to global protein
      synthesis. Leucine also stimulated phosphorylation of the ribosomal protein S6
      kinase, p70(S6k), resulting in increased phosphorylation of S6.
      Hyperphosphorylation of S6 was associated with a 4-fold increase in synthesis of
      elongation factor eEF1A. Rapamycin, an inhibitor of the protein kinase mTOR,
      prevented all of the leucine-induced effects. Thus, leucine acting through an
      mTOR-dependent pathway stimulates the translation of specific mRNAs both by
      increasing the availability of eIF4E and by stimulating phosphorylation of S6.

PMID- 10206977
TI  - Cloning of murine translation initiation factor 6 and functional analysis of the
      homologous sequence YPR016c in Saccharomyces cerevisiae.
AB  - The cDNA sequence of a murine gene whose expression was up-regulated after
      epidermal injury was cloned utilizing differential display. The full-length cDNA
      was isolated by 3' and 5' rapid amplification of cDNA ends from mouse liver. The
      predicted protein is >97% identical to the human sequence for eukaryotic
      translation initiation factor (eIF) 6, thus identifying the gene as murine eIF6.
      Functional studies of the yeast eIF6 homolog, YPR016c, were initiated in
      Saccharomyces cerevisiae to determine the cellular role(s) of eIF6. Complete
      deletion of the YPR016c coding sequence was lethal. Viability was restored in the
      presence of either YPR016c or murine eIF6, when either was expressed as amino
      terminal green fluorescent protein fusion protein. Moreover, both fusion proteins
      localized to nuclear/perinuclear compartments in their respective yeast strains.
      When the expression of YPR016c-green fluorescent protein was repressed, there was
      a dramatic reduction in the 60 S ribosomal subunit and polysome content and
      decreased 80S monosome content. Additionally, the YPR016c-depleted cells arrested
      in G1. These studies show that YPR016c, which encodes yeast eIF6, is necessary
      for maximal polysome formation and plays an important role in determining free 60
      S ribosomal subunit content.

PMID- 10206978
TI  - Arachidonic acid is preferentially metabolized by cyclooxygenase-2 to
      prostacyclin and prostaglandin E2.
AB  - The two cyclooxygenase isoforms, cyclooxygenase-1 and cyclooxygenase-2, both
      metabolize arachidonic acid to prostaglandin H2, which is subsequently processed
      by downstream enzymes to the various prostanoids. In the present study, we asked
      if the two isoforms differ in the profile of prostanoids that ultimately arise
      from their action on arachidonic acid. Resident peritoneal macrophages contained
      only cyclooxygenase-1 and synthesized (from either endogenous or exogenous
      arachidonic acid) a balance of four major prostanoids: prostacyclin, thromboxane
      A2, prostaglandin D2, and 12-hydroxyheptadecatrienoic acid. Prostaglandin E2 was
      a minor fifth product, although these cells efficiently converted exogenous
      prostaglandin H2 to prostaglandin E2. By contrast, induction of cyclooxygenase-2
      with lipopol- ysaccharide resulted in the preferential production of prostacyclin
      and prostaglandin E2. This shift in product profile was accentuated if
      cyclooxygenase-1 was permanently inactivated with aspirin before cyclooxygenase-2
      induction. The conversion of exogenous prostaglandin H2 to prostaglandin E2 was
      only modestly increased by lipopolysaccharide treatment. Thus, cyclooxygenase-2
      induction leads to a shift in arachidonic acid metabolism from the production of
      several prostanoids with diverse effects as mediated by cyclooxygenase-1 to the
      preferential synthesis of two prostanoids, prostacyclin and prostaglandin E2,
      which evoke common effects at the cellular level.

PMID- 10206979
TI  - Lipopolysaccharide-induced tumor necrosis factor-alpha promoter activity is
      inhibitor of nuclear factor-kappaB kinase-dependent.
AB  - The adverse effects of lipopolysaccharide (LPS) are primarily mediated by tumor
      necrosis factor-alpha (TNF-alpha). TNF-alpha production by LPS-stimulated
      macrophages is regulated both transcriptionally and post-transcriptionally.
      Transcriptional regulation of the TNF-alpha gene is dependent on nuclear factor
      kappaB (NF-kappaB). We examined the signaling pathways involved in the regulation
      of NF-kappaB that lead to TNF-alpha promoter activity. We determined a role for
      one or both of the recently identified inhibitor of NF-kappaB kinases, IkappaB
      kinase-1 and IkappaB kinase-2, in LPS induction of an NF-kappaB reporter and of
      TNF-alpha promoter activity. IkappaB kinase activation is one of the earliest
      signaling events known to be induced by LPS. Furthermore, our results suggest
      roles for the IkappaB kinases NF-kappaB-inducing kinase and mitogen-activated
      protein kinase/extracellular signal-regulated kinase kinase kinase 1 in the
      regulation of IkappaB kinase-2, as well as in LPS-induced TNF-alpha
      transcription.

PMID- 10206980
TI  - The CREB constitutive activation domain interacts with TATA-binding protein
      associated factor 110 (TAF110) through specific hydrophobic residues in one of
      the three subdomains required for both activation and TAF110 binding.
AB  - The cAMP response element-binding protein (CREB) mediates both basal and PKA
      inducible transcription through two separate and independently active domains,
      the constitutive activation domain (CAD) and the kinase-inducible domain,
      respectively. The CREB CAD interacts with the general transcription factor TFIID
      through one or more of the TATA-binding protein-associated factors (TAFs), one of
      which is TAF110. The CAD is composed of three subdomains, rich in either serine,
      hydrophobic amino acids, or glutamine. In the present study, analysis of deletion
      mutants of the CAD showed that all three CAD subdomains were required for
      effective interaction with TAF110 in a yeast two-hybrid assay. Therefore, a
      library of random point mutations within the CAD was analyzed in a reverse two
      hybrid screen to identify amino acids that are essential for interaction with the
      TAF. Interaction defects resulted solely from mutations of hydrophobic amino acid
      residues within the hydrophobic cluster to charged amino acid residues. Together,
      the deletion and mutation analyses suggest that the entire CAD provides an
      environment for a specific hydrophobic interaction with TAF110 that is crucial
      for interaction. Our results provide further evidence for a model of basal
      activation by CREB involving interaction with TAF110 that promotes recruitment or
      stabilization of TFIID binding to the promoter, which facilitates pre-initiation
      complex assembly.

PMID- 10206981
TI  - The glucocorticoid response element II is functionally homologous in rat and
      human insulin-like growth factor-binding protein-1 promoters.
AB  - In vivo, insulin-like growth factor-binding protein-1 (IGFBP-1) modulates the
      IGFs' bioavailability and may contribute to their delivery to peripheral tissues.
      In rat and human hepatocytes, glucocorticoids stimulate IGFBP-1 gene
      transcription through homologous glucocorticoid response units (GRU).
      Transfection experiments have shown that one of these, GRU2 (nucleotide (nt) -121
      to -85 and nt -111 to -74 in human and rat promoters, respectively), was on its
      own able to mediate the glucocorticoid response in rat but not in human species
      (Suwanichkul, A., Allander, S., Morris, S. L. & Powell, D. R. (1994) J. Biol.
      Chem. 269, 30835-30841, Goswami, R., Lacson, R., Yang, E., Sam, R. & Unterman, T.
      (1994) Endocrinology 134, 736-743, and Suh, D. S., Ooi, G. T. & Rechler, M. M.
      (1994) Mol. Endocrinol. 8, 794-805). A close comparison of GRU2 sequences has
      pointed out a C to A transition in the underlying GREII, which creates a GATC
      tetranucleotide in rat species. This tetranucleotide is submitted to adenosyl
      methylation (dam methylation) in most Escherichia coli bacterial strains, but not
      in eucaryotic cells. We showed (i) that on its own, the unmethylated rat GRU2
      (propagated in dam E. coli strains) was inactive, as is the case for its human
      counterpart (nonsignificant glucocorticoid inductions, 1.48 +/- 0.23 and 1.7 +/-
      0.35-fold in Chinese hamster ovary cells, respectively) and (ii) that its
      adenosyl methylation in standard dam+ bacterial strains yielded a functional GRU
      (6.5 +/- 1. 1 and 13.1 +/- 3.9-fold glucocorticoid inductions in Chinese hamster
      ovary and HepG2 cells, respectively). Transient transfection in HepG2 hepatoma
      cells clearly showed that the interaction of liver-enriched trans-acting
      factor(s) with the 5'-overlapping insulin response element does not enable the
      unmethylated rat GRU2 or the human GRU2 to become responsive to glucocorticoids
      (nonsignificant 2.21 +/- 0.48 and 1.20 +/- 0.06-fold induction, respectively).
      Furthermore, we have correlated these functional data with in vitro DNA-protein
      interaction studies: the dam methylated rat GREII displayed a 2.8-fold higher
      affinity for the glucocorticoid receptor than its unmethylated counterpart.

PMID- 10206982
TI  - Identification of three cysteines as targets for the Zn2+ blockade of the human
      skeletal muscle chloride channel.
AB  - Currents through the human skeletal muscle chloride channel hClC-1 can be blocked
      by external application of 1 mM Zn2+ or the histidine-reactive compound diethyl
      pyrocarbonate (DEPC). The current block by Zn2+ strongly depends on the external
      pH (pKa near 6.9), whereas the block by DEPC is rather independent of the pH in
      the range of 5.5 to 8.5. To identify the target sites of these reagents, we
      constructed a total of twelve cysteine- and/or histidine-replacement mutants,
      transfected tsA201 cells with them, and investigated the resulting whole-cell
      chloride currents. The majority of the mutants exhibited a similar sensitivity
      toward Zn2+ or DEPC as wild type (WT) channels. Block by 1 mM Zn2+ was nearly
      absent only with the mutant C546A. Four mutants (C242A, C254A, H180A, and H451A)
      were slightly less sensitive to Zn2+ than WT. Tests with double, triple, and
      quadruple mutants yielded that, in addition to C546, C242 and C254 are also most
      likely participating in Zn2+-binding.

PMID- 10206983
TI  - Inhibition of T cell signaling by mitogen-activated protein kinase-targeted
      hematopoietic tyrosine phosphatase (HePTP).
AB  - Activation of T lymphocytes to produce cytokines is regulated by the
      counterbalance of protein-tyrosine kinases and protein-tyrosine phosphatases,
      many of which have a high degree of substrate specificity because of physical
      association with their targets. Overexpression of hematopoietic protein-tyrosine
      phosphatase (HePTP) results in suppression of T lymphocyte activation as measured
      by T cell antigen receptor-induced activation of transcription factors binding to
      the 5' promoter of the interleukin-2 gene. Efforts to pinpoint the exact site of
      action and specificity of HePTP in the signaling cascade revealed that HePTP acts
      directly on the mitogen-activated protein (MAP) kinases Erk1 and 2 and
      consequently reduces the magnitude and duration of their catalytic activation in
      intact T cells. In contrast, HePTP had no effects on N-terminal c-Jun kinase or
      on events upstream of the MAP kinases. The specificity of HePTP correlated with
      its physical association through its noncatalytic N terminus with Erk and another
      MAP kinase, p38, but not Jnk or other proteins. We propose that HePTP plays a
      negative role in antigen receptor signaling by specifically regulating MAP
      kinases in the cytosol and at early time points of T cell activation before the
      activation-induced expression of nuclear dual-specific MAP kinase phosphatases.

PMID- 10206984
TI  - Autocrine regulation of volume-sensitive anion channels in airway epithelial
      cells by adenosine.
AB  - The activity of volume-sensitive Cl- channels was studied in human tracheal
      epithelial cells (9HTEo-) by taurine efflux experiments. The efflux elicited by a
      hypotonic shock was partially inhibited by adenosine receptor antagonists, by
      alpha,beta-methyleneadenosine 5'-diphosphate (alphabetaMeADP), an inhibitor of
      the 5'-ectonucleotidase, and by adenosine deaminase. On the other hand,
      dipyridamole, a nucleoside transporter inhibitor, increased the swelling-induced
      taurine efflux. Extracellular ATP and adenosine increased taurine efflux by
      potentiating the effect of hypotonic shock. alphabetaMeADP strongly inhibited the
      effect of extracellular ATP but not that of adenosine. These results suggest that
      anion channel activation involves the release of intracellular ATP, which is then
      degraded to adenosine by specific ectoenzymes. Adenosine then binds to purinergic
      receptors, causing the activation of the channels. To directly demonstrate ATP
      efflux, cells were loaded with [3H]AMP, and the release of radiolabeled molecules
      was analyzed by high performance liquid chromatography. During hypotonic shock,
      cell supernatants showed the presence of ATP, ADP, and adenosine. alphabetaMeADP
      inhibited adenosine formation and caused the appearance of AMP. Under hypotonic
      conditions, elevation of intracellular Ca2+ by ionomycin caused an increase of
      ATP and adenosine in the extracellular solution. Our results demonstrate that
      volume-sensitive anion channels are regulated with an autocrine mechanism
      involving swelling-induced ATP release and then hydrolysis to adenosine.

PMID- 10206985
TI  - Testis-specific TTF-D binds to single-stranded DNA in the c-mos and Odf1
      promoters and activates Odf1.
AB  - We recently identified testis-specific nuclear factor binding sites in the testis
      specific promoters of the c-mos gene and the Odf1 gene, which are 80% identical.
      Here we characterize a testis-specific nuclear factor, TTF-D, which is able to
      complex with both binding sites and stimulates Odf1 promoter activity. TTF-D is
      detectable in mouse testis as early as day 11 postpartum and contains three
      peptides of 22, 25, and 35 kDa in size. Surprisingly, TTF-D binds specifically to
      its cognate double-stranded DNA binding site as well as to its single-stranded
      DNA binding site. Both double-stranded and single-stranded binding site
      oligonucleotide DNA can specifically repress Odf1 promoter activity. Our results
      suggest that TTF-D is involved in positive transcription regulation of a pre
      meiotic and a post-meiotic gene in the testis.

PMID- 10206986
TI  - A new family of human histone deacetylases related to Saccharomyces cerevisiae
      HDA1p.
AB  - Histone deacetylases are the catalytic subunits of multiprotein complexes that
      are targeted to specific promoters through their interaction with sequence
      specific DNA-binding factors. We have cloned and characterized a new human cDNA,
      HDAC-A, with homology to the yeast HDA1 family of histone deacetylases. Analysis
      of the predicted amino acid sequence of HDAC-A revealed an open reading frame of
      967 amino acids containing two domains: a NH2-terminal domain with no homology to
      known proteins and a COOH-terminal domain with homology to known histone
      deacetylases (42% similarity to RPD3, 60% similarity to HDA1). Three additional
      human cDNAs with high homology to HDAC-A were identified in sequence data bases,
      indicating that HDAC-A itself is a member of a new family of human histone
      deacetylases. The mRNA encoding HDAC-A was differentially expressed in a variety
      of human tissues. The expressed protein, HDAC-Ap, exhibited histone deacetylase
      activity and this activity mapped to the COOH-terminal region (amino acids 495
      967) with homology to HDA1p. In immunoprecipitation experiments, HDAC-A
      interacted specifically with several cellular proteins, indicating that it might
      be part of a larger multiprotein complex.

PMID- 10206987
TI  - Endostatin induces endothelial cell apoptosis.
AB  - Endostatin, a carboxyl-terminal fragment of collagen XVIII, has been shown to
      regress tumors in mice. In this study, we have analyzed the mechanism of
      endostatin action on endothelial cells and nonendothelial cells. Endostatin
      treatment of cow pulmonary artery endothelial cells caused apoptosis, as
      demonstrated by three methods, annexin V-fluorescein isothiocyanate staining,
      caspase 3, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end
      labeling assay. Moreover, addition of endostatin led to a marked reduction of the
      Bcl-2 and Bcl-XL anti-apoptotic protein, whereas Bax protein levels were
      unaffected. These effects were not seen in several nonendothelial cells.
      Collectively, these findings provide important mechanistic insight into
      endostatin action.

PMID- 10206988
TI  - A hemocyte-like cell line established from the malaria vector Anopheles gambiae
      expresses six prophenoloxidase genes.
AB  - Cell lines from the malaria vector Anopheles gambiae have been established as a
      tool for the study of the mosquito innate immune system in vitro. Here, we
      describe the first continuous insect cell line that produces prophenoloxidase
      (PPO). This cell line (4a-3B) expresses constitutively six PPO genes, three of
      which are novel (PPO4, PPO5, and PPO6). The PPO genes show distinct temporal
      expression profiles in the intact mosquito, spanning stages from the embryo to
      the adult in an overlapping manner. Transient induction of larva-specific PPO
      genes in blood-fed adult females suggests that the developmental hormone 20
      hydroxyecdysone may be involved in PPO gene regulation. Indeed, exposure of 4a-3B
      cells to 20-hydroxyecdysone in culture results in induction of those PPO genes
      that are mainly expressed in early developmental stages, and repression of PPO5,
      which is preferentially expressed at the adult stage. The cell line shows
      bacteria-induced immune transcripts that encode defensin and Gram-negative
      bacteria-binding protein, but no induction of PPO transcripts. This cell line
      most likely derives from a hemocyte lineage, and represents an appropriate in
      vitro model for the study of the humoral and cellular immune defenses of A.
      gambiae.

PMID- 10206989
TI  - Interaction of neuronal nitric-oxide synthase with alpha1-syntrophin in rat
      brain.
AB  - Neuronal nitric-oxide synthase (nNOS) has a PSD-95/Dlg/ZO-1 (PDZ) domain that can
      interact with multiple proteins. nNOS has been known to interact with PSD-95 and
      a related protein, PSD-93, in brain and with alpha1-syntrophin in skeletal muscle
      in mammals. In this study, we have purified an nNOS-interacting protein from
      bovine brain using an affinity column made of Sepharose conjugated with
      glutathione S-transferase-rat nNOS fusion protein and identified it as alpha1
      syntrophin by microsequencing. Immunostaining of primary cultures of rat
      embryonic brain neuronal cells with antibodies against these proteins showed that
      nNOS and alpha1-syntrophin were colocalized in neuronal cell bodies and neurites.
      Immunohistochemical analysis indicated that the nNOS- and alpha1-syntrophin-like
      immunoreactive substances were highly expressed in the rat hypothalamic
      suprachiasmatic nucleus (SCN) and paraventricular nucleus. In the SCN, nNOS- and
      alpha1-syntrophin-like immunoreactive substances were colocalized in the same
      neurons as detected by confocal microscopy. These results indicate that nNOS in
      brain interacts with alpha1-syntrophin in specific neurons of the SCN and
      paraventricular nucleus and that this interaction might play a physiological role
      in functions of these neurons.

PMID- 10206990
TI  - Purification, cDNA cloning, and expression of a new human blood plasma glutamate
      carboxypeptidase homologous to N-acetyl-aspartyl-alpha-glutamate
      carboxypeptidase/prostate-specific membrane antigen.
AB  - We describe the identification, cDNA cloning, and biochemical characterization of
      a new human blood plasma glutamate carboxypeptidase (PGCP). PGCP was co-purified
      from human placenta with lysosomal carboxypeptidase, cathepsin A, lysosomal
      endopeptidase, cathepsin D, and a gamma-interferon-inducible protein, IP-30,
      using an affinity chromatography on a Phe-Leu-agarose column. A PGCP cDNA was
      obtained as an expressed sequence tag clone and completed at 5'-end by rapid
      amplification of cDNA ends polymerase chain reaction. The cDNA contained a 1623
      base pair open reading frame predicting a 541-amino acid protein, with five
      putative Asn glycosylation sites and a 21-residue signal peptide. PGCP showed
      significant amino acid sequence homology to several cocatalytic metallopeptidases
      including a glutamate carboxypeptidase II also known as N-acetyl-aspartyl-alpha
      glutamate carboxypeptidase or as prostate-specific membrane antigen and expressed
      glutamate carboxypeptidase activity. Expression of the PGCP cDNA in COS-1 cells,
      followed by Western blotting and metabolic labeling showed that PGCP is
      synthesized as a 62-kDa precursor, which is processed to a 56-kDa mature form
      containing two Asn-linked oligosaccharide chains. The mature form of PGCP was
      secreted into the culture medium, which is consistent with its intracellular
      localization in secretion granules. In humans, PGCP is found principally in blood
      plasma, suggesting a potential role in the metabolism of secreted peptides.

PMID- 10206991
TI  - Cloning of a new mouse two-P domain channel subunit and a human homologue with a
      unique pore structure.
AB  - Mouse KCNK6 is a new subunit belonging to the TWIK channel family. This 335-amino
      acid polypeptide has four transmembrane segments, two pore-forming domains, and a
      Ca2+-binding EF-hand motif. Expression of KCNK6 transcripts is principally
      observed in eyes, lung, stomach and embryo. In the eyes, immunohistochemistry
      reveals protein expression only in some of the retina neurons. Although KCNK6 is
      able to dimerize as other functional two-P domain K+ channels when it is
      expressed in COS-7 cells, it remains in the endoplasmic reticulum and is unable
      to generate ionic channel activity. Deletions, mutations, and chimera
      constructions suggest that KCNK6 is not an intracellular channel but rather a
      subunit that needs to associate with a partner, which remains to be discovered,
      in order to reach the plasma membrane. A closely related human KCNK7-A subunit
      has been cloned. KCNK7 displays an intriguing GLE sequence in its filter region
      instead of the G(Y/F/L)G sequence, which is considered to be the K+ channel
      signature. This subunit is alternatively spliced and gives rise to the shorter
      forms KCNK7-B and -C. None of the KCNK7 structures can generate channel activity
      by itself. The KCNK7 gene is situated on chromosome 11, in the q13 region, where
      several candidate diseases have been identified.

PMID- 10206992
TI  - Structural basis for cold adaptation. Sequence, biochemical properties, and
      crystal structure of malate dehydrogenase from a psychrophile Aquaspirillium
      arcticum.
AB  - Aquaspillium arcticum is a psychrophilic bacterium that was isolated from arctic
      sediment and grows optimally at 4 degrees C. We have cloned, purified, and
      characterized malate dehydrogenase from A. arcticum (Aa MDH). We also have
      determined the crystal structures of apo-Aa MDH, Aa MDH.NADH binary complex, and
      Aa MDH.NAD.oxaloacetate ternary complex at 1.9-, 2.1-, and 2.5-A resolutions,
      respectively. The Aa MDH sequence is most closely related to the sequence of a
      thermophilic MDH from Thermus flavus (Tf MDH), showing 61% sequence identity and
      over 90% sequence similarity. Stability studies show that Aa MDH has a half-life
      of 10 min at 55 degrees C, whereas Tf MDH is fully active at 90 degrees C for 1
      h. Aa MDH shows 2-3-fold higher catalytic efficiency compared with a mesophilic
      or a thermophilic MDH at the temperature range 4-10 degrees C. Structural
      comparison of Aa MDH and Tf MDH suggests that the increased relative flexibility
      of active site residues, favorable surface charge distribution for substrate and
      cofactor, and the reduced intersubunit ion pair interactions may be the major
      factors for the efficient catalytic activity of Aa MDH at low temperatures.

PMID- 10206993
TI  - Differential mechanisms of recognition and activation of interleukin-8 receptor
      subtypes.
AB  - We have probed an epitope sequence (His18-Pro19-Lys20-Phe21) in interleukin-8 (IL
      8) by site-directed mutagenesis. This work shows that single and double Ala
      substitutions of His18 and Phe21 in IL-8 reduced up to 77-fold the binding
      affinity to IL-8 receptor subtypes A (CXCR1) and B (CXCR2) and to the Duffy
      antigen. These Ala mutants triggered neutrophil degranulation and induced calcium
      responses mediated by CXCR1 and CXCR2. Single Asp or Ser substitutions, H18D,
      F21D, F21S, and double substitutions, H18A/F21D, H18A/F21S, and H18D/F21D,
      reduced up to 431-fold the binding affinity to CXCR1, CXCR2, and the Duffy
      antigen. Interestingly, double mutants with charged residue substitutions failed
      to trigger degranulation or to induce wild-type calcium responses mediated by
      CXCR1. Except for the H18A and F21A mutants, all other IL-8 mutants failed to
      induce superoxide production in neutrophils. This study demonstrates that IL-8
      recognizes and activates CXCR1, CXCR2, and the Duffy antigen by distinct
      mechanisms.

PMID- 10206994
TI  - A pivotal role for the transmembrane domain in transforming growth factor-beta
      receptor activation.
AB  - Transforming growth factor-beta (TGF-beta) delivers diverse growth and
      differentiation signals by binding two distantly related transmembrane
      serine/threonine kinase receptors: the type I receptor (TbetaRI) and the type II
      receptor (TbetaRII). In an attempt to establish the role of the transmembrane
      domain in receptor signaling, two chimeric TGF-beta receptors, TbetaRI-II-I and
      TbetaRII-I-II, containing the opposite transmembrane domain were generated. When
      transfected into a mutant mink lung epithelial cell line R1B, which lacks
      functional TbetaRI, TbetaRI-II-I restored TGF-beta1-induced transcriptional
      activation of a TGF-beta reporter p3TP-Lux to approximately 25% of the levels
      restored by wild-type TbetaRI. In the mutant mink lung epithelial cell line DR26,
      which contains a truncated, nonfunctional TbetaRII, wild-type receptor TbetaRII
      restored the TGF-beta responsiveness, while the TbetaRII-I-II cDNA was inactive.
      When both TbetaRI and TbetaRII were transfected into R1B, DR26, or Mv1Lu cells, a
      low level of constitutive p3TP-Lux activity was observed. However, cotransfection
      of both transmembrane chimeric receptors, TbetaRI-II-I and TbetaRII-I-II, or the
      wild-type TbetaRI with the transmembrane chimeric TbetaRII-I-II resulted in high
      levels of ligand-independent receptor activation. These results suggest that the
      transmembrane domains of both TGF-beta receptors are essential and play a pivotal
      role in receptor activation. To investigate the role of the transmembrane domain
      further, four type II transmembrane mutants were generated: TbetaRIIDelta-1,
      TbetaRIIDelta-2, TbetaRIIDelta-3, and TbetaRIIDelta-4, which have one, two,
      three, or four amino acids deleted at the N terminus of the transmembrane domain,
      respectively. Interestingly, co-expression of TbetaRIIDelta-1 with the wild-type
      TbetaRI in DR26 cells resulted in high levels of constitutive activation, while
      only low levels of the activation were observed when TbetaRIIDelta-2,
      TbetaRIIDelta-3, or TbetaRIIDelta-4 were co-expressed with the wild-type TbetaRI.
      However, TbetaRIIDelta-1 restored very little the TGF-beta responsiveness in
      DR26cells. Expression of TbetaRIIDelta-2, TbetaRIIDelta-3, and TbetaRIIDelta-4
      resulted in a progressive increase in TGF-beta responsiveness, with TbetaRIIDelta
      4 reaching the level of activity of the wild-type TbetaRII. Furthermore, like
      TbetaRII-I-II, co-expression of TbetaRIIDelta-1 with TbetaRI-II-I also resulted
      in high levels of constitutive activation. These results are consistent with an
      important role for the transmembrane region of the receptors. We further propose
      a model of receptor activation in which receptor activation occurs via relative
      orientational rotation.

PMID- 10206995
TI  - Disruption of disulfide bonds is responsible for impaired secretion in human
      complement factor H deficiency.
AB  - Factor H, a secretory glycoprotein composed of 20 short consensus repeat modules,
      is an inhibitor of the complement system. Previous studies of inherited factor H
      deficiency revealed single amino acid substitutions at conserved cysteine
      residues, on one allele arginine for cysteine 518 (C518R) and on the other
      tyrosine for cysteine 941 (C941Y) (Ault, B. H., Schmidt, B. Z., Fowler, N. L.,
      Kashtan, C. E., Ahmed, A. E., Vogt, B. A., and Colten, H. R. (1997) J. Biol.
      Chem. 272, 25168-25175). To ascertain if the phenotype, impaired secretion of
      factor H, is due to the C518R substitution or the C941Y substitution and to
      ascertain the mechanism by which secretion is impaired, we studied COS-1 and
      HepG2 cells transfected with wild type and several mutant factor H molecules. The
      results showed markedly impaired secretion of both C518R and C941Y factor H as
      well as that of factor H molecules bearing alanine or arginine substitutions at
      the Cys518-Cys546 disulfide bond (C518A, C546A, C546R, C518A-C546A). In each
      case, mutant factor H was retained in the endoplasmic reticulum and degraded
      relatively slowly as compared with most other mutant secretory and membrane
      proteins that are retained in the endoplasmic reticulum. These data indicate that
      impaired secretion of the naturally occurring C518R and C941Y mutant factor H
      proteins is due to disruption of framework-specific disulfide bonds in factor H
      short consensus repeat modules.

PMID- 10206996
TI  - Neurite outgrowth in PC12 cells. Distinguishing the roles of ubiquitylation and
      ubiquitin-dependent proteolysis.
AB  - Nerve growth factor (NGF)-induced neurite outgrowth from rat PC12 cells was
      coincident with elevated (>/=2-fold) levels of endogenous ubiquitin (Ub) protein
      conjugates, elevated rates of formation of 125I-labeled Ub approximately E1 (Ub
      activating enzyme) thiol esters and 125I-labeled Ub approximately E2 (Ub carrier
      protein) thiol esters in vitro, and enhanced capacity to synthesize 125I-labeled
      Ub-protein conjugates de novo. Activities of at least four E2s were increased in
      NGF-treated cells, including E2(14K), a component of the N-end rule pathway.
      Ubiquitylation of 125 I-labeled beta-lactoglobulin was up to 4-fold greater in
      supernatants from NGF-treated cells versus untreated cells and was selectively
      inhibited by the dipeptide Leu-Ala, an inhibitor of Ub isopeptide ligase (E3).
      However, Ub-dependent proteolysis of 125I-labeled beta-lactoglobulin was not
      increased in supernatants from NGF-treated cells, suggesting that neurite
      outgrowth is promoted by enhanced rates of synthesis (rather than degradation) of
      Ub-protein conjugates. Consistent with this observation, neurite outgrowth was
      induced by proteasome inhibitors (lactacystin and clasto-lactacystin beta
      lactone) and was associated with elevated levels of ubiquitylated protein and
      stabilization of the Ub-dependent substrate, p53. Lactacystin-induced neurite
      outgrowth was blocked by the dipeptide Leu-Ala (2 mM) but not by His-Ala. These
      data 1) demonstrate that the enhanced pool of ubiquitylated protein observed
      during neuritogenesis in PC12 cells reflects coordinated up-regulation of Ub
      conjugating activity, 2) suggest that Ub-dependent proteolysis is a negative
      regulator of neurite outgrowth in vitro, and 3) support a role for E2(14K)/E3
      mediated protein ubiquitylation in PC12 cell neurite outgrowth.

PMID- 10206997
TI  - Association with the SRC family tyrosyl kinase LYN triggers a conformational
      change in the catalytic region of human cAMP-specific phosphodiesterase
      HSPDE4A4B. Consequences for rolipram inhibition.
AB  - The cAMP-specific phosphodiesterase (PDE) HSPDE 4A4B(pde46) selectively bound SH3
      domains of SRC family tyrosyl kinases. Such an interaction profoundly changed the
      inhibition of PDE4 activity caused by the PDE4-selective inhibitor rolipram and
      mimicked the enhanced rolipram inhibition seen for particulate, compared with
      cytosolic pde46 expressed in COS7 cells. Particulate pde46 co-localized with LYN
      kinase in COS7 cells. The unique N-terminal and LR2 regions of pde46 contained
      the sites for SH3 binding. Altered rolipram inhibition was triggered by SH3
      domain interaction with the LR2 region. Purified LYN SH3 and human PDE4A LR2
      could be co-immunoprecipitated, indicating a direct interaction. Protein kinase A
      phosphorylated pde46 remained able to bind LYN SH3. pde46 was found to be
      associated with SRC kinase in the cytosol of COS1 cells, leading to aberrant
      kinetics of rolipram inhibition. It is suggested that pde46 may be associated
      with SRC family tyrosyl kinases in intact cells and that the ensuing SH3 domain
      interaction with the LR2 region of pde46 alters the conformation of the PDE
      catalytic unit, as detected by altered rolipram inhibition. Interaction between
      pde46 and SRC family tyrosyl kinases highlights a potentially novel regulatory
      system and point of signaling system cross-talk.

PMID- 10206998
TI  - The cystic fibrosis transmembrane conductance regulator activates aquaporin 3 in
      airway epithelial cells.
AB  - Enhanced osmotic water permeability has been observed in Xenopus oocytes
      expressing cystic fibrosis transmembrane conductance regulator (CFTR) protein.
      Subsequent studies have shown that CFTR activates an endogenous water
      permeability in oocytes, but that CFTR itself is not the water channel. Here, we
      show CFTR-dependent activation of endogenous water permeability in normal but not
      in cystic fibrosis human airway epithelial cells. Cell volume was measured by
      novel confocal x-z laser scanning microscopy. Glycerol uptake and antisense
      studies suggest CFTR-dependent regulation of aquaporin 3 (AQP3) water channels in
      airway epithelial cells. Regulatory interaction was confirmed by coexpression of
      CFTR and AQP3 cloned from human airways in Xenopus oocytes and of CFTR and rat
      AQP3 in Chinese hamster ovary cells. These findings indicate that CFTR is a
      regulator of AQP3 in airway epithelial cells.

PMID- 10206999
TI  - The structure and unusual pH dependence of plastocyanin from the fern Dryopteris
      crassirhizoma. The protonation of an active site histidine is hindered by pi-pi
      interactions.
AB  - Spectroscopic properties, amino acid sequence, electron transfer kinetics, and
      crystal structures of the oxidized (at 1.7 A resolution) and reduced form (at 1.8
      A resolution) of a novel plastocyanin from the fern Dryopteris crassirhizoma are
      presented. Kinetic studies show that the reduced form of Dryopteris plastocyanin
      remains redox-active at low pH, under conditions where the oxidation of the
      reduced form of other plastocyanins is inhibited by the protonation of a solvent
      exposed active site residue, His87 (equivalent to His90 in Dryopteris
      plastocyanin). The x-ray crystal structure analysis of Dryopteris plastocyanin
      reveals pi-pi stacking between Phe12 and His90, suggesting that the active site
      is uniquely protected against inactivation. Like higher plant plastocyanins,
      Dryopteris plastocyanin has an acidic patch, but this patch is located closer to
      the solvent-exposed active site His residue, and the total number of acidic
      residues is smaller. In the reactions of Dryopteris plastocyanin with inorganic
      redox reagents, the acidic patch (the "remote" site) and the hydrophobic patch
      surrounding His90 (the "adjacent" site) are equally efficient for electron
      transfer. These results indicate the significance of the lack of protonation at
      the active site of Dryopteris plastocyanin, the equivalence of the two electron
      transfer sites in this protein, and a possibility of obtaining a novel insight
      into the photosynthetic electron transfer system of the first vascular plant
      fern, including its molecular evolutionary aspects. This is the first report on
      the characterization of plastocyanin and the first three-dimensional protein
      structure from fern plant.

PMID- 10207001
TI  - A human papillomavirus E2 transcriptional activator. The interactions with
      cellular splicing factors and potential function in pre-mRNA processing.
AB  - The human papillomavirus (HPV) E2 protein plays an important role in
      transcriptional regulation of viral genes as well as in viral DNA replication.
      Unlike most types of HPV, the E2 protein of epidermodysplasia verruciformis (EV)
      associated HPVs harbors a relatively long hinged region between the terminal,
      conserved transactivation and DNA binding/dimerization domains. The sequence of
      EV-HPV E2 hinge contains multiple arginine/serine (RS) dipeptide repeats which
      are characteristic of a family of pre-messenger RNA splicing factors, called SR
      proteins. Here we show that the HPV-5 (an EV-HPV) E2 protein can specifically
      interact with cellular splicing factors including a set of prototypical SR
      proteins and two snRNP-associated proteins. Transiently expressed HPV-5 E2
      protein colocalizes with a nuclear matrix associated-splicing coactivator in
      nuclear speckled domains. The RS-rich hinge is essential for E2 transactivator
      interaction with splicing factors and for its subnuclear localization. Moreover,
      we present functional evidence for the HPV-5 E2 transactivator, which shows that
      the RS-rich hinge domain of the E2 protein can facilitate the splicing of
      precursor messenger RNA made via transactivation by E2 itself. Our results,
      therefore, suggest that a DNA binding transactivator containing an RS-rich
      sequence can play a dual role in gene expression.

PMID- 10207000
TI  - Expression, characterization, and mutagenesis of the Yersinia pestis murine
      toxin, a phospholipase D superfamily member.
AB  - A phospholipase D (PLD) superfamily was recently identified that contains
      proteins of highly diverse functions with the conserved motif HXKX4DX6G(G/S). The
      superfamily includes a bacterial nuclease, human and plant PLD enzymes,
      cardiolipin synthases, phosphatidylserine synthases, and the murine toxin from
      Yersinia pestis (Ymt). Ymt is particularly effective as a prototype for family
      members containing two conserved motifs, because it is smaller than many other
      two-domain superfamily enzymes, and it can be overexpressed. Large quantities of
      pure recombinant Ymt allowed the formation of diffraction-quality crystals for x
      ray structure determination. Dimeric Ymt was shown to have PLD-like activity as
      demonstrated by the hydrolysis of phosphatidylcholine. Ymt also used bis(para
      nitrophenol) phosphate as a substrate. Using these substrates, the amino acids
      essential for Ymt function were determined. Specifically, substitution of
      histidine or lysine in the conserved motifs reduced the turnover rate of bis(para
      nitrophenol) phosphate by a factor of 10(4) and phospholipid turnover to an
      undetectable level. The role of the conserved residues in catalysis was further
      defined by the isolation of a radiolabeled phosphoenzyme intermediate, which
      identified a conserved histidine residue as the nucleophile in the catalytic
      reaction. Based on these data, a unifying two-step catalytic mechanism is
      proposed for this diverse family of enzymes.

PMID- 10207002
TI  - Quantitative and qualitative analysis of type III antifreeze protein structure
      and function.
AB  - Some cold water marine fishes avoid cellular damage because of freezing by
      expressing antifreeze proteins (AFPs) that bind to ice and inhibit its growth;
      one such protein is the globular type III AFP from eel pout. Despite several
      studies, the mechanism of ice binding remains unclear because of the difficulty
      in modeling the AFP-ice interaction. To further explore the mechanism, we have
      determined the x-ray crystallographic structure of 10 type III AFP mutants and
      combined that information with 7 previously determined structures to mainly
      analyze specific AFP-ice interactions such as hydrogen bonds. Quantitative
      assessment of binding was performed using a neural network with properties of the
      structure as input and predicted antifreeze activity as output. Using the cross
      validation method, a correlation coefficient of 0.60 was obtained between
      measured and predicted activity, indicating successful learning and good
      predictive power. A large loss in the predictive power of the neural network
      occurred after properties related to the hydrophobic surface were left out,
      suggesting that van der Waal's interactions make a significant contribution to
      ice binding. By combining the analysis of the neural network with antifreeze
      activity and x-ray crystallographic structures of the mutants, we extend the
      existing ice-binding model to a two-step process: 1) probing of the surface for
      the correct ice-binding plane by hydrogen-bonding side chains and 2) attractive
      van der Waal's interactions between the other residues of the ice-binding surface
      and the ice, which increases the strength of the protein-ice interaction.

PMID- 10207003
TI  - Identification of the calmodulin-binding domain of neuron-specific protein kinase
      C substrate protein CAP-22/NAP-22. Direct involvement of protein myristoylation
      in calmodulin-target protein interaction.
AB  - Various proteins in the signal transduction pathways as well as those of viral
      origin have been shown to be myristoylated. Although the modification is often
      essential for the proper functioning of the modified protein, the mechanism by
      which the modification exerts its effects is still largely unknown. Brain
      specific protein kinase C substrate, CAP-23/NAP-22, which is involved in the
      synaptogenesis and neuronal plasticity, binds calmodulin, but the protein lacks
      any canonical calmodulin-binding domain. In the present report, we show that CAP
      23/NAP-22 isolated from rat brain is myristoylated and that the modification is
      directly involved in its interaction with calmodulin. Myristoylated and non
      myristoylated recombinant proteins were produced in Escherichia coli, and their
      calmodulin-binding properties were examined. Only the former bound to calmodulin.
      Synthetic peptides based on the N-terminal sequence showed similar binding
      properties to calmodulin, only when they were myristoylated. The calmodulin
      binding site narrowed down to the myristoyl moiety together with a nine-amino
      acid N-terminal basic domain. Phosphorylation of a single serine residue in the N
      terminal domain (Ser5) by protein kinase C abolished the binding. Furthermore,
      phosphorylation of CAP-23/NAP-22 by protein kinase C was also found
      myristoylation-dependent, suggesting the importance of myristoylation in protein
      protein interactions.

PMID- 10207004
TI  - A pattern recognition protein for peptidoglycan. Cloning the cDNA and the gene of
      the silkworm, Bombyx mori.
AB  - Peptidoglycan recognition protein (PGRP) specifically binds to peptidoglycan and
      is considered to be one of the pattern recognition proteins in the innate
      immunity of insect. The PGRP is an essential component for peptidoglycan to
      trigger the prophenoloxidase cascade that is now recognized to be an important
      insect defense mechanism. We cloned cDNA encoding PGRP from the silkworm fat body
      cDNA library. Northern blot analysis showed that the PGRP gene is constitutively
      expressed in the fat body, epithelial cell, and hemocytes of naive silkworms.
      Furthermore, a bacterial challenge intensified the gene expression, with the
      maximal period being from 6 to 36 h after infection. The upstream sequence of the
      cloned PGRP gene was shown to contain putative cis-regulatory elements similar to
      the NF-kappaB-like element, interferon-response half-element, and GATA motif
      element, which have been found in the promoters of the acute phase protein genes
      of mammals and insects. A homology search revealed that the homologs of silkworm
      PGRP are present in mice, nematodes, and bacteriophages. This suggests that the
      recognition of peptidoglycan as foreign is effected in both vertebrates and
      invertebrates by PGRP homologs with an evolutionally common origin.

PMID- 10207006
TI  - The cytoplasmic domain of the lymphotoxin-beta receptor mediates cell death in
      HeLa cells.
AB  - Activation of lymphotoxin-beta receptor (LT-betaR) by conjugation with
      heterotrimeric lymphotoxin, LT-alpha1/beta2, or by cross-linking with anti-LT
      betaR antibodies can trigger apoptosis. We have observed that overexpression of
      either LT-betaR or the cytoplasmic domain of LT-betaR (LT-betaR(CD)) also induces
      apoptosis, which may be attributed to the tendency of LT-betaR(CD) to self
      associate. The self-association domain of LT-betaR(CD) was mapped to amino acids
      324-377, a region of the protein that is also essential for LT-betaR-induced
      apoptosis. Furthermore, we have shown that LT-betaR(CD)-induced apoptosis could
      be inhibited by a TRAF3 dominant negative mutant and by the caspase inhibitors Z
      VAD-FMK, DEVD-FMK, and CrmA. The ligand-independent apoptosis induced by LT
      betaR(CD) will help us to further dissect LT-betaR signaling pathway.

PMID- 10207005
TI  - Receptor recognition sites of cytokines are organized as exchangeable modules.
      Transfer of the leukemia inhibitory factor receptor-binding site from ciliary
      neurotrophic factor to interleukin-6.
AB  - Interleukin-6 (IL-6) and ciliary neurotrophic factor (CNTF) are "4-helical
      bundle" cytokines of the IL-6 type family of neuropoietic and hematopoietic
      cytokines. IL-6 signals by induction of a gp130 homodimer (e.g. IL-6), whereas
      CNTF and leukemia inhibitory factor (LIF) signal via a heterodimer of gp130 and
      LIF receptor (LIFR). Despite binding to the same receptor component (gp130) and a
      similar protein structure, IL-6 and CNTF share only 6% sequence identity. Using
      molecular modeling we defined a putative LIFR binding epitope on CNTF that
      consists of three distinct regions (C-terminal A-helix/N-terminal AB loop, BC
      loop, C-terminal CD-loop/N-terminal D-helix). A corresponding gp130-binding site
      on IL-6 was exchanged with this epitope. The resulting IL-6/CNTF chimera lost the
      capacity to signal via gp130 on cells without LIFR, but acquired the ability to
      signal via the gp130/LIFR heterodimer and STAT3 on responsive cells. Besides
      identifying a specific LIFR binding epitope on CNTF, our results suggest that
      receptor recognition sites of cytokines are organized as modules that are
      exchangeable even between cytokines with limited sequence homology.

PMID- 10207007
TI  - Control of the cell morphology and the S phase entry by mitogen-activated protein
      kinase kinase. A regulatory role of its n-terminal region.
AB  - The mitogen-activated protein kinase kinase (MAPKK)/MAP kinase (MAPK) cascade
      plays an important role in the growth control of mammalian cells. We have found
      that expression of constitutively active MAPKK induces rapid morphological
      changes of fibroblastic cells, which are accompanied by disruption of stress
      fibers and disappearance of focal adhesions. These changes took place under the
      conditions that inhibited cellular Ras function, suggesting a linkage between the
      MAPK cascade and the control of cell morphology. We further show that
      constitutively active MAPKK can induce expression of endogenous Fos protein, an
      immediately early gene product, and cause the S phase entry of G0-arrested cells.
      Finally, expression of the N-terminal fragment of MAPKK which encompasses the
      nuclear export signal sequence and the MAPK-binding site blocked both the serum
      induced S phase entry of quiescent cells and the oncogenic Ras-induced
      morphological changes. All these results demonstrate that MAPKK is one of key
      molecules involved in the control of both cell morphology and cell proliferation
      and suggest an important role for the N-terminal region of MAPKK in the
      regulation of the MAPK signaling.

PMID- 10207008
TI  - Roles of Trp31 in high membrane binding and proinflammatory activity of human
      group V phospholipase A2.
AB  - Group V phospholipase A2 is a recently discovered secretory phospholipase A2
      (PLA2) that has been shown to be involved in eicosanoid formation in inflammatory
      cells, such as macrophages and mast cells. We have demonstrated that human group
      V PLA2 (hsPLA2-V) can bind phosphatidylcholine (PC) membranes and hydrolyze PC
      substrates much more efficiently than human group IIa PLA2, which makes it better
      suited for acting on the outer plasma membrane (Han, S.-K., Yoon, E. T., and Cho,
      W. (1998) Biochem. J. 331, 353-357). In this study, we demonstrate that exogenous
      hsPLA2-V has much greater activity than does group IIa PLA2 to release fatty
      acids from various mammalian cells and to elicit leukotriene B4 formation from
      human neutrophils. To understand the molecular basis of these activities, we
      mutated two surface tryptophans of hsPLA2-V to alanine (W31A and W79A) and
      measured the effects of these mutations on the kinetic activity toward various
      substrates, on the binding affinity for vesicles and phospholipid-coated beads,
      on the penetration into phospholipid monolayers, and on the activity to release
      fatty acids and elicit eicosanoid formation from various mammalian cells. These
      studies show that the relatively high ability of hsPLA2-V to induce cellular
      eicosanoid formation derives from its high affinity for PC membranes and that
      Trp31 on its putative interfacial binding surface plays an important role in its
      binding to PC vesicles and to the outer plasma membrane.

PMID- 10207009
TI  - MAGUIN, a novel neuronal membrane-associated guanylate kinase-interacting
      protein.
AB  - Postsynaptic density (PSD)-95/Synapse-associated protein (SAP) 90 and synaptic
      scaffolding molecule (S-SCAM) are neuronal membrane-associated guanylate kinases.
      Because PSD-95/SAP90 and S-SCAM function as synaptic scaffolding proteins,
      identification of ligands for these proteins is important to elucidate the
      structure of synaptic junctions. Here, we report a novel protein interacting with
      the PDZ domains of PSD-95/SAP90 and S-SCAM and named it MAGUIN-1 (membrane
      associated guanylate kinase-interacting protein-1). MAGUIN-1 has one sterile
      alpha motif, one PDZ, and one plekstrin homology domain. MAGUIN-1 is localized at
      the plasma membrane via the plekstrin homology domain and the C-terminal region
      and interacts with PSD-95/SAP90 and S-SCAM via a C-terminal PDZ domain-binding
      motif. MAGUIN-1 has a short isoform, MAGUIN-2, which lacks a PDZ domain-binding
      motif. MAGUINs are expressed in neurons and localized in the cell body and
      neurites and are coimmunoprecipitated with PSD-95/SAP90 and S-SCAM from rat crude
      synaptosome. MAGUIN-1 may play an important role with PSD-95/SAP90 and S-SCAM to
      assemble the components of synaptic junctions.

PMID- 10207010
TI  - Activation of the GP IIb-IIIa complex induced by platelet adhesion to collagen is
      mediated by both alpha2beta1 integrin and GP VI.
AB  - alpha2beta1 integrin, CD36, and GP VI have all been implicated in platelet
      collagen adhesive interactions. We have investigated the role of these
      glycoproteins on activation of the GP IIb-IIIa complex induced by platelet
      adhesion to type I fibrillar and monomeric collagen under static conditions. In
      the presence of Mg2+, platelet adhesion to fibrillar collagen induced activation
      of the GP IIb-IIIa complex and complete spreading. Anti-alpha2beta1 integrin and
      anti-GP VI antibodies inhibited the activation of the GP IIb-IIIa complex by
      about 40 and 50%, respectively, at 60 min although minimal inhibitory effects on
      adhesion were seen. Platelet spreading was markedly reduced by anti-alpha2beta1
      integrin antibody. The combination of anti-alpha2beta1 integrin with anti-GP VI
      antibody completely inhibited both platelet adhesion and activation of the GP IIb
      IIIa complex. Anti-CD36 antibody had no significant effects on platelet adhesion,
      spreading, and the activation of the GP IIb-IIIa complex at 60 min. Aspirin and
      the thromboxane A2 receptor antagonist SQ29548 inhibited activation of the GP IIb
      IIIa complex about 30% but had minimal inhibitory effect on adhesion. In the
      absence of Mg2+, there was significant activation of the GP IIb-IIIa complex but
      minimal spreading was observed. Anti-GP VI antibody completely inhibited adhesion
      whereas no effect was observed with anti-alpha2beta1 integrin antibody. Anti-CD36
      antibody partially inhibited both adhesion and the activation of the GP IIb-IIIa
      complex. Platelet adhesion to monomeric collagen, which requires Mg2+ and is
      exclusively mediated by alpha2beta1 integrin, resulted in partial activation of
      the GPIIb-IIIa complex and spreading. No significant effects were observed by
      anti-CD36 and anti-GP VI antibodies. These results suggest that both alpha2beta1
      integrin and GP VI are involved in inside-out signaling leading to activation of
      the GP IIb-IIIa complex after platelet adhesion to collagen and generation of
      thromboxane A2 may further enhance expression of activated GP IIb-IIIa complexes.

PMID- 10207011
TI  - The three-dimensional structure of a Tn5 transposase-related protein determined
      to 2.9-A resolution.
AB  - Transposon Tn5 employs a unique means of self-regulation by expressing a
      truncated version of the transposase enzyme that acts as an inhibitor. The
      inhibitor protein differs from the full-length transposase only by the absence of
      the first 55 N-terminal amino acid residues. It contains the catalytic active
      site of transposase and a C-terminal domain involved in protein-protein
      interactions. The three-dimensional structure of Tn5 inhibitor determined to 2.9
      A resolution is reported here. A portion of the protein fold of the catalytic
      core domain is similar to the folds of human immunodeficiency virus-1 integrase,
      avian sarcoma virus integrase, and bacteriophage Mu transposase. The Tn5
      inhibitor contains an insertion that extends the beta-sheet of the catalytic core
      from 5 to 9 strands. All three of the conserved residues that make up the "DDE"
      motif of the active site are visible in the structure. An arginine residue that
      is strictly conserved among the IS4 family of bacterial transposases is present
      at the center of the active site, suggesting a catalytic motif of "DDRE." A novel
      C-terminal domain forms a dimer interface across a crystallographic 2-fold axis.
      Although this dimer represents the structure of the inhibited complex, it
      provides insight into the structure of the synaptic complex.

PMID- 10207012
TI  - gamma-Secretase, evidence for multiple proteolytic activities and influence of
      membrane positioning of substrate on generation of amyloid beta peptides of
      varying length.
AB  - gamma-Secretase activity is the final cleavage event that releases the amyloid
      beta peptide (Abeta) from the beta-secretase cleaved carboxyl-terminal fragment
      of the amyloid beta protein precursor (APP). No protease responsible for this
      highly unusual, purportedly intramembranous, cleavage has been definitively
      identified. We examined the substrate specificity of gamma-secretase by mutating
      various residues within or adjacent to the transmembrane domain of the APP and
      then analyzing Abeta production from cells transfected with these mutant APPs by
      enzyme-linked immunosorbent assay and mass spectrometry. Abeta production was
      also analyzed from a subset of transmembrane domain APP mutants that showed
      dramatic shifts in gamma-secretase cleavage in the presence or absence of
      pepstatin, an inhibitor of gamma-secretase activity. These studies demonstrate
      that gamma-secretase's cleavage specificity is primarily determined by location
      of the gamma-secretase cleavage site of APP with respect to the membrane, and
      that gamma-secretase activity is due to the action of multiple proteases
      exhibiting both a pepstatin- sensitive activity and a pepstatin-insensitive
      activity. Given that gamma-secretase is a major therapeutic target in Alzheimer's
      disease these studies provide important information with respect to the mechanism
      of Abeta production that will direct efforts to isolate the gamma-secretases and
      potentially to develop effective therapeutic inhibitors of pathologically
      relevant gamma-secretase activities.

PMID- 10207013
TI  - Inflammatory cytokines and oxidized low density lipoproteins increase endothelial
      cell expression of membrane type 1-matrix metalloproteinase.
AB  - We investigated whether inflammatory cytokines or oxidized low density
      lipoproteins (Ox-LDL) present in human atheroma modulate extracellular matrix
      degradation by inducing membrane type 1-matrix metalloproteinase (MT1-MMP)
      expression. Cultured human endothelial cells (EC) constitutively expressed MT1
      MMP mRNA and protein with enzymatic activity. Tumor necrosis factor-alpha (TNF
      alpha), interleukin-1alpha, or interleukin-1beta caused a time-dependent increase
      in the steady-state MT1-MMP mRNA levels within 4 h of exposure, peaking about 4
      fold by 6 h, and remaining elevated for 12 h. Increased MT1-MMP mRNA correlated
      with a 2.5-fold increase in MT1-MMP protein in EC membranes. Ox-LDL also
      increased MT1-MMP mRNA levels that varied with the duration of exposure and
      degree of LDL oxidation. The increase in MT1-MMP mRNA occurred within 6 h of
      exposure to Ox-LDL and peaked over 3-fold by 6 h. Ox-LDL, but not native LDL,
      increased MT1-MMP protein by 2-fold in EC membranes. A combination of TNF-alpha
      and Ox-LDL was additive in increasing MT1-MMP expression. Nuclear run-on assays
      showed that TNF-alpha or Ox-LDL augmented steady-state mRNA levels by increased
      transcription of the MT1-MMP gene. These findings indicate that activation of EC
      by inflammatory cytokines and/or Ox-LDL increase MT1-MMP expression. Since MT1
      MMP promotes matrix degradation by activating pro-MMP-2, these results suggest a
      novel mechanism whereby cytokines or Ox-LDL may influence extracellular matrix
      remodeling.

PMID- 10207015
TI  - Characterization of the entire transcription unit of the mouse fibroblast growth
      factor 1 (FGF-1) gene. Tissue-specific expression of the FGF-1.A mRNA.
AB  - Fibroblast growth factor 1 (FGF-1, also known as acidic FGF) is a mitogen for a
      variety of mesoderm- and neuroectoderm-derived cells, as well as an angiogenic
      factor in vivo. It has been implicated in angiogenic diseases including
      atherosclerosis, cancer and inflammatory diseases. In the present study, the
      entire transcriptional unit of the mouse FGF-1 gene, including four promoters, is
      characterized. By nucleotide sequence and RNase protection analyses, we have
      determined that its 3'-end resides 3.2 kilobase pairs downstream from the stop
      codon. We have previously cloned and characterized the mouse homologue of the
      human 1B promoter, as well as a novel upstream untranslated exon. In order to
      elucidate the regulatory mechanism of FGF-1 gene expression, the mouse promoter
      containing TATA and CAAT consensus sequences (FGF-1. A) was isolated from a P1
      library and characterized. We further determined that the mouse heart is the most
      abundant source for the FGF-1.A mRNA. Finally, via both RNase protection analysis
      and 5'-rapid amplification of cDNA ends, we determined the transcription start
      site of the FGF-1.A mRNA.

PMID- 10207014
TI  - Sequences within fibrinogen and intercellular adhesion molecule-1 (ICAM-1)
      modulate signals required for mitogenesis.
AB  - The interaction of fibrinogen (Fg) with intercellular adhesion molecule-1 (ICAM)
      on B-lymphoid Raji cells results in mitogenesis (Gardiner, E. E., and D'Souza, S.
      E. (1997) J. Biol. Chem. 272, 15474-15480). Incubation of Raji with Fg resulted
      in the increased tyrosine phosphorylation of the receptor-associated tyrosine
      kinase, pp60(Src) and extracellular signal-regulated kinase-1 (ERK). The increase
      in ERK-1 phosphorylation was blocked by a peptide with sequence matching ICAM-1
      (8-22) and corresponded to a decrease in ERK-1 enzymatic activity. 100 microM
      amounts of Fg peptide gamma-(117-133) caused an increase in tyrosine
      phosphorylation of ERK-1. These results are consistent with our previous report
      wherein ICAM-1-(8-22) blocked Fg-induced mitogenesis and Fg-gamma-(117-133)
      induced proliferation in Raji. The specific inhibitor of MEK, PD98059 (25
      microM), abrogated the increased phosphorylation of ERK-1 and blocked Raji
      mitogenesis by >50%. Inhibitors of pp60(Src), geldanamycin (62 nM), and
      herbimycin A (2.5 microM) blocked >50% of Raji proliferation. These results
      indicate that the proliferation induced by Fg interactions with ICAM-1 is
      mediated in part by receptor-associated tyrosine kinases and ERK-1, and that the
      recognition sequences within Fg and ICAM-1 participate in the signaling process.

PMID- 10207016
TI  - Analysis of the pre-S2 N- and O-linked glycans of the M surface protein from
      human hepatitis B virus.
AB  - The surface antigen of hepatitis B virus comprises a nested set of small (S),
      middle (M), and large (L) proteins, all of which are partially glycosylated in
      their S domains. The pre-S2 domain, present only in M and L proteins, is further
      N-glycosylated at Asn-4 exclusively in the M protein. Since the pre-S2 N-glycan
      appears to play a crucial role in the secretion of viral particles, the M protein
      may be considered as a potential target for antiviral therapy. For
      characterization of the pre-S2 glycosylation, pre-S2 (glyco)peptides were
      released from native, patient-derived hepatitis B virus subviral particles by
      tryptic digestion, separated from remaining particles, purified by reversed-phase
      high performance liquid chromatography, and identified by amino acid and N
      terminal sequence analysis as well as matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry (MALDI-TOF-MS). Pre-S2 N-glycans were
      characterized by anion exchange chromatography, methylation analysis, and on
      target sequential exoglycosidase digestions in combination with MALDI-TOF-MS,
      demonstrating the presence of partially sialylated diantennary complex-type
      oligosaccharides. In addition, the pre-S2 domain of M protein, but not that of L
      protein, was found to be partially O-glycosylated by a Gal(beta1-3)GalNAcalpha-,
      Neu5Ac(alpha2-3)Gal(beta1-3)GalNAcalpha-, or GalNAcalpha-residue. The respective
      O-glycosylation site was assigned to Thr-37 by digestion with carboxypeptidases
      in combination with MALDI-TOF-MS and by quadrupole time-of-flight electrospray
      mass spectrometry. Analytical data further revealed that about 90% of M protein
      is N-terminally acetylated.

PMID- 10207017
TI  - Molecular cloning and functional expression of two members of mouse
      NeuAcalpha2,3Galbeta1,3GalNAc GalNAcalpha2,6-sialyltransferase family, ST6GalNAc
      III and IV.
AB  - Two cDNA clones encoding NeuAcalpha2,3Galbeta1,3GalNAc GalNAcalpha2, 6
      sialyltransferase have been isolated from mouse brain cDNA libraries. One of the
      cDNA clones is a homologue of previously reported rat ST6GalNAc III according to
      the amino acid sequence identity (94.4%) and the substrate specificity of the
      expressed recombinant enzyme, while the other cDNA clone includes an open reading
      frame coding for 302 amino acids. The deduced amino acid sequence is not
      identical to those of other cloned mouse sialyltransferases, although it shows
      the highest sequence similarity with mouse ST6GalNAc III (43.0%). The expressed
      soluble recombinant enzyme exhibited activity toward NeuAcalpha2, 3Galbeta1,
      3GalNAc, fetuin, and GM1b, while no significant activity was detected toward
      Galbeta1,3GalNAc or asialofetuin, or the other glycoprotein substrates tested.
      The sialidase sensitivity of the 14C-sialylated residue of fetuin, which was
      sialylated by this enzyme with CMP-[14C]NeuAc, was the same as that of ST6GalNAc
      III. These results indicate that the expressed enzyme is a new type of
      GalNAcalpha2,6-sialyltransferase, which requires sialic acid residues linked to
      Galbeta1,3GalNAc residues for its activity; therefore, we designated it mouse
      ST6GalNAc IV. Although the substrate specificity of this enzyme is similar to
      that of ST6GalNAc III, ST6GalNAc IV prefers O-glycans to glycolipids.
      Glycolipids, however, are better substrates for ST6GalNAc III.

PMID- 10207018
TI  - Characterization of the 70-kDa peroxisomal membrane protein, an ATP binding
      cassette transporter.
AB  - The 70-kDa peroxisomal membrane protein (PMP70) is one of the major components of
      rat liver peroxisomal membranes and belongs to a superfamily of proteins known as
      ATP binding cassette transporters. PMP70 is markedly induced by administration of
      hypolipidemic agents in parallel with peroxisome proliferation and induction of
      peroxisomal fatty acid beta-oxidation enzymes. To characterize the role of PMP70
      in biogenesis and function of peroxisomes, we transfected the cDNA of rat PMP70
      into Chinese hamster ovary cells and established cell lines stably expressing
      PMP70. The content of PMP70 in the transfectants increased about 5-fold when
      compared with the control cells. A subcellular fractionation study showed that
      overexpressed PMP70 was enriched in peroxisomes. This peroxisomal localization
      was confirmed by immunofluorescence and immunoelectron microscopy. The number of
      immuno-gold particles corresponding to PMP70 on peroxisomes increased markedly in
      the transfectants, but the size and the number of peroxisomes were essentially
      the same in both the transfectants and the control cells. beta-Oxidation of
      palmitic acid increased about 2-3-fold in the transfectants, whereas the
      oxidation of lignoceric acid decreased about 30-40%. When intact peroxisomes
      prepared from both the cell lines were incubated with palmitoyl-CoA, oxidation
      was stimulated with ATP, but the degree of the stimulation was higher in the
      transfectants than in the control cells. Furthermore, we established three
      Chinese hamster ovary cell lines stably expressing mutant PMP70. In these cells,
      beta-oxidation of palmitic acid decreased markedly. These results suggest that
      PMP70 is involved in metabolic transport of long chain acyl-CoA across
      peroxisomal membranes and that increase of PMP70 is not associated with
      proliferation of peroxisomes.

PMID- 10207019
TI  - Intra-M phase-promoting factor phosphorylation of cyclin B at the
      prophase/metaphase transition.
AB  - Activation of Cdc2-cyclin B (or M phase-promoting factor (MPF)) at the
      prophase/metaphase transition proceeds in two steps: dephosphorylation of Cdc2
      and phosphorylation of cyclin B. We here investigated the regulation of cyclin B
      phosphorylation using the starfish oocyte model. Cyclin B phosphorylation is not
      required for Cdc2 kinase activity; both the prophase complex dephosphorylated on
      Cdc2 with Cdc25 and the metaphase complex dephosphorylated on cyclin B with
      protein phosphatase 2A display high kinase activities. An in vitro assay of
      cyclin B kinase activity closely mimics in vivo phosphorylation as shown by
      phosphopeptide maps of in vivo and in vitro phosphorylated cyclin B. We
      demonstrate that Cdc2 itself is the cyclin B kinase; cyclin B phosphorylation
      requires Cdc2 activity both in vivo (sensitivity to vitamin K3, a Cdc25
      inhibitor) and in vitro (copurification with Cdc2-cyclin B, requirement of Cdc2
      dephosphorylation, and sensitivity to chemical inhibitors of cyclin-dependent
      kinases). Furthermore, cyclin B phosphorylation occurs as an intra-M phase
      promoting factor reaction as shown by the following: 1) active Cdc2 is unable to
      phosphorylate cyclin B associated to phosphorylated Cdc2, and 2) cyclin B
      phosphorylation is insensitive to enzyme/substrate dilution. We conclude that, at
      the prophase/metaphase transition, cyclin B is mostly phosphorylated by its own
      associated Cdc2 subunit.

PMID- 10207020
TI  - Biochemical characterization and functional analysis of two type II classic
      cadherins, cadherin-6 and -14, and comparison with E-cadherin.
AB  - Classic cadherins can be grouped based on their deduced primary structures. Among
      them the type I cadherins have been well characterized; however, little is known
      about non-type I cadherins. In this study we characterized two human type II
      cadherins, cadherin-6 and cadherin-14, using a cDNA transfection system. They
      were each detected as two bands electrophoretically, were expressed on the
      external cell surface at cell-cell contact sites, and were associated with caten-
      ins. Direct sequencing of the N-terminal amino acids showed that the two bands of
      cadherin-14 corresponded to precursor and mature forms, whereas the two bands of
      cadherin-6 both had the N-terminal sequence of the mature form. Unlike type I
      cadherins, both cadherin-6 and -14 were not protected from trypsin degradation by
      Ca2+. We evaluated their adhesive functions by a long term cell aggregation
      method. The results suggest that both cadherin-6 and -14 have cell-cell binding
      strengths virtually equivalent to that of E-cadherin and that their binding
      specificities are distinct from that of E-cadherin. Cadherin-6 and -14 interacted
      with each other in an incomplete manner. They have a QAI tripeptide in the first
      extracellular subdomain instead of the HAV motif that is characteristic of type I
      cadherins and is intimately involved in the adhesive function. The QAI
      tripeptide, however, appeared not to be involved in the adhesive functions of
      cadherin-6 and -14.

PMID- 10207021
TI  - Adhesion of cultured bovine aortic endothelial cells to laminin-1 mediated by
      dystroglycan.
AB  - Expression of dystroglycan (DG) by cultured bovine aortic endothelial (BAE) cells
      was confirmed by cDNA cloning from a BAE cDNA library, Northern blotting of mRNA,
      Western blotting of membrane proteins, and double immunostaining with antibodies
      against betaDG and platelet endothelial cell adhesion molecule-1.
      Immunocytochemical analysis revealed localization of DG in multiple plaques on
      the basal side of resting cells. This patchy distribution was obscured in
      migrating cells, in which the most prominent staining was observed in the
      trailing edge anchoring the cells to the substratum. Biotin-labeled laminin-1
      overlay assay of dissociated BAE membrane proteins indicated the interaction of
      laminin-1 with alphaDG. The laminin alpha5 globular domain fragment expressed in
      bacteria and labeled with biotin could also bind alphaDG on the membrane blot,
      and the unlabeled fragment disrupted the binding of biotin-laminin-1 to alphaDG.
      The interaction of biotin-laminin-1 with alphaDG was inhibited by soluble alphaDG
      contained in the conditioned medium from DG cDNA-transfected BAE cells and by a
      series of glycosaminoglycans (heparin, dextran sulfate, and fucoidan). Soluble
      alphaDG in the conditioned medium inhibited the adhesion of BAE cells to laminin
      1-coated dishes, whereas it had no effect on their adhesion to fibronectin. All
      three glycosaminoglycans that disrupted the biotin-laminin-1 binding to alphaDG
      inhibited BAE cell adhesion to laminin-1, whereas they failed to inhibit the
      adhesion to fibronectin. These results indicate a role of DG as a non-integrin
      laminin receptor involved in vascular endothelial cell adhesion to the
      extracellular matrix.

PMID- 10207022
TI  - Interaction of plant chimeric calcium/calmodulin-dependent protein kinase with a
      homolog of eukaryotic elongation factor-1alpha.
AB  - A chimeric Ca2+/calmodulin-dependent protein kinase (CCaMK) was previously cloned
      and characterized in this laboratory. To investigate the biological functions of
      CCaMK, the yeast two-hybrid system was used to isolate genes encoding proteins
      that interact with CCaMK. One of the cDNA clones obtained from the screening
      (LlEF-1alpha1) has high similarity with the eukaryotic elongation factor-1alpha
      (EF-1alpha). CCaMK phosphorylated LlEF-1alpha1 in a Ca2+/calmodulin-dependent
      manner. The phosphorylation site for CCaMK (Thr-257) was identified by site
      directed mutagenesis. Interestingly, Thr-257 is located in the putative tRNA
      binding region of LlEF-1alpha1. An isoform of Ca2+-dependent protein kinase
      (CDPK) phosphorylated multiple sites of LlEF-1alpha1 in a Ca2+-dependent but
      calmodulin-independent manner. Unlike CDPK, CCaMK phosphorylated only one site,
      and this site is different from CDPK phosphorylation sites. This suggests that
      the phosphorylation of EF-1alpha by these two kinases may have different
      functional significance. Although the phosphorylation of LlEF-1alpha1 by CCaMK is
      Ca2+/calmodulin-dependent, in vitro binding assays revealed that CCaMK binds to
      LlEF-1alpha1 in a Ca2+-independent manner. This was further substantiated by
      coimmunoprecipitation of CCaMK and EF-1alpha using the protein extract from lily
      anthers. Dissociation of CCaMK from EF-1alpha by Ca2+ and phosphorylation of EF
      1alpha by CCaMK in a Ca2+/calmodulin-dependent manner suggests that these
      interactions may play a role in regulating the biological functions of EF-1alpha.

PMID- 10207023
TI  - Modulation of E2F complexes during G0 to S phase transition in human primary B
      lymphocytes.
AB  - The pocket protein-E2F complexes are convergence points for cell cycle signaling.
      In the present report, we identified and monitored the pocket protein-E2F
      complexes in human primary B-lymphocytes after activation by phorbol 12-myristate
      13-acetate. Consistent with previous data from human and mouse fibroblasts and T
      lymphocytes, E2F4 and DP1 form the predominant E2F heterodimers both in G0 and G1
      phases of the human B-lymphocyte cell cycle, whereas E2F1 and -3 are first
      detected in late G1, and their expression levels increase towards S phase.
      Intriguingly, the major E2F complex that we detected in quiescent human B
      lymphocytes is consisted of pRB, E2F4, and DP1. Though the levels of DP1 and -2
      increase when cells progress from G0 to S, the proportion of DP1 to DP2 remains
      relatively constant during the cell cycle. We also observed an increase in
      electrophoretic mobility of the predominant E2F components, DP1 and E2F4, as B
      lymphocytes progressed from G0 into early G1. This increase in mobility was
      attributable to dephosphorylation, as lambda phosphatase treatment could convert
      the slower migrating forms into the corresponding faster mobility forms. We
      further demonstrated that this change in phosphorylation status correlates with a
      decrease in DNA binding activity. This modulation of DNA binding activity
      mediated through the dephosphorylation of DP1 and E2F4 could help to explain the
      lack of in vivo DNA footprinting in late G1 and S phases of gene promoters
      negatively regulated through E2F sites and suggests a novel mechanism for
      controlling E2F transcriptional activity during the transition from quiescence to
      proliferation.

PMID- 10207024
TI  - The beta3-adrenergic receptor activates mitogen-activated protein kinase in
      adipocytes through a Gi-dependent mechanism.
AB  - Promiscuous coupling between G protein-coupled receptors and multiple species of
      heterotrimeric G proteins provides a potential mechanism for expanding the
      diversity of G protein-coupled receptor signaling. We have examined the mechanism
      and functional consequences of dual Gs/Gi protein coupling of the beta3
      adrenergic receptor (beta3AR) in 3T3-F442A adipocytes. The beta3AR selective
      agonist disodium (R, R)-5-[2[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino]propyl]-1,
      3-benzodioxole-2,2-dicarboxylate (CL316,243) stimulated a dose-dependent increase
      in cAMP production in adipocyte plasma membrane preparations, and pretreatment of
      cells with pertussis toxin resulted in a further 2-fold increase in cAMP
      production by CL316,243. CL316,243 (5 microM) stimulated the incorporation of 8
      azido-[32P]GTP into Galphas (1.57 +/- 0.12; n = 3) and Galphai (1. 68 +/- 0.13; n
      = 4) in adipocyte plasma membranes, directly demonstrating that beta3AR
      stimulation results in Gi-GTP exchange. The beta3AR-stimulated increase in 8
      azido-[32P]GTP labeling of Galphai was equivalent to that obtained with the A1
      adenosine receptor agonist N6-cyclopentyladenosine (1.56 +/- 0.07; n = 4),
      whereas inclusion of unlabeled GTP (100 microM) eliminated all binding.
      Stimulation of the beta3AR in 3T3-F442A adipocytes led to a 2-3-fold activation
      of mitogen-activated protein (MAP) kinase, as measured by extracellular signal
      regulated kinase-1 and -2 (ERK1/2) phosphorylation. Pretreatment of cells with
      pertussis toxin (PTX) eliminated MAP kinase activation by beta3AR, demonstrating
      that this response required receptor coupling to Gi. Expression of the human
      beta3AR in HEK-293 cells reconstituted the PTX-sensitive stimulation of MAP
      kinase, demonstrating that this phenomenon is not exclusive to adipocytes or to
      the rodent beta3AR. ERK1/2 activation by the beta3AR was insensitive to the cAMP
      dependent protein kinase inhibitor H-89 but was abolished by genistein and
      AG1478. These data indicate that constitutive beta3AR coupling to Gi proteins
      serves both to restrain Gs-mediated activation of adenylyl cyclase and to
      initiate additional signal transduction pathways, including the ERK1/2 MAP kinase
      cascade.

PMID- 10207025
TI  - Molecular mechanisms of peptide loading by the tumor rejection antigen/heat shock
      chaperone gp96 (GRP94).
AB  - Complexes of gp96/GRP94 and peptides have been shown to elicit immunogenicity. We
      used fluorescence to understand peptide association with gp96. A pyrene-peptide
      conjugate was complexed with gp96 under a variety of conditions. At room
      temperature in low salt (20 mM NaCl), the peptide binds gp96 with a strong
      affinity (approximately 100-150 nM) and forms pyrene excimers, suggesting that
      the peptides were assembled as dimers. In high salt (2.2 M NaCl), although
      peptide binding was stronger (Ka approximately 55 nM) than in low salt, pyrene
      excimers were absent, implying that peptides were farther apart in the complex.
      Heat shock-activated peptide binding exhibited characteristics of both low salt
      and high salt modes of binding. Anisotropy and average lifetime of the bound
      pyrene suggested that peptides were probably located in a solvent-accessible
      hydrophobic binding pocket in low salt, whereas in high salt, the peptide may be
      buried in a less hydrophobic (more hydrophilic) environment. These results
      suggested that peptide-gp96 complexes were assembled in several different ways,
      depending on the assembly conditions. Resonance energy transfer between the
      intrinsic tryptophan(s) in gp96 and pyrene suggested that one or more tryptophan
      residues were within the critical Forster distance of 27-30 A from the pyrene in
      the bound peptide. It is proposed that peptides are assembled within higher order
      gp96 complexes (dimers, etc.) in a hydrophobic pocket and that there may be a
      conformational change in gp96 leading to an open configuration for peptide
      loading.

PMID- 10207026
TI  - Identification of the activating and conjugating enzymes of the NEDD8 conjugation
      pathway.
AB  - NEDD8 is a ubiquitin-like molecule that can be covalently conjugated to a limited
      number of cellular proteins, such as Cdc53/cullin. We have previously reported
      that the C terminus of NEDD8 is efficiently processed to expose Gly-76, which is
      required for conjugation to target proteins. A combination of data base searches
      and polymerase chain reaction cloning was used to identify a cDNA encoding human
      UBA3, which is 38% identical to the yeast homologue, 22% identical to human UBA2,
      and 19% identical to the C-terminal region of human UBE1. The human UBA3 gene is
      located on chromosome 3p13 and gave rise to a 2.2-kilobase pair transcript that
      was detected in all tissues. Human UBA3 could be precipitated with glutathione S
      transferase (GST)-NEDD8, but not with GST-ubiquitin or GST-sentrin-1. Moreover,
      human UBA3 could form a beta-mercaptoethanol-sensitive conjugate with NEDD8 in
      the presence of APP-BP1, a protein with sequence homology to the N-terminal half
      of ubiquitin-activating enzyme. We have also cloned human UBC12 and demonstrated
      that it could form a thiol ester linkage with NEDD8 in the presence of the
      activating enzyme complex. Identification of the activating and conjugating
      enzymes of the NEDD8 conjugation pathway should allow for a more detailed study
      of the role of NEDD8 modification in health and disease.

PMID- 10207027
TI  - The class B, type I scavenger receptor promotes the selective uptake of high
      density lipoprotein cholesterol ethers into caveolae.
AB  - The uptake of cholesterol esters from high density lipoproteins (HDLs) is
      characterized by the initial movement of cholesterol esters into a reversible
      plasma membrane pool. Cholesterol esters are subsequently internalized to a
      nonreversible pool. Unlike the uptake of cholesterol from low density
      lipoproteins, cholesterol ester uptake from HDL does not involve the
      internalization and degradation of the particle and is therefore termed
      selective. The class B, type I scavenger receptor (SR-BI) has been identified as
      an HDL receptor and shown to mediate selective cholesterol ester uptake. SR-BI is
      localized to cholesterol- and sphingomyelin-rich microdomains called caveolae.
      Caveolae are directly involved in cholesterol trafficking. Therefore, we tested
      the hypothesis that caveolae are acceptors for HDL-derived cholesterol ether
      (CE). Our studies demonstrate that in Chinese hamster ovary cells expressing SR
      BI, >80% of the plasma membrane associated CE is present in caveolae after 7.5
      min of selective cholesterol ether uptake. We also show that excess, unlabeled
      HDL can extract the radiolabeled CE from caveolae, demonstrating that caveolae
      constitute a reversible plasma membrane pool of CE. Furthermore, 50% of the
      caveolae-associated CE can be chased into a nonreversible pool. We conclude that
      caveolae are acceptors for HDL-derived cholesterol ethers, and that caveolae
      constitute a reversible, plasma membrane pool of cholesterol ethers.

PMID- 10207028
TI  - Association of sterol- and glycosylphosphatidylinositol-linked proteins with
      Drosophila raft lipid microdomains.
AB  - In vertebrates, the formation of raft lipid microdomains plays an important part
      in both polarized protein sorting and signal transduction. To establish a system
      in which raft-dependent processes could be studied genetically, we have analyzed
      the protein and lipid composition of these microdomains in Drosophila
      melanogaster. Using mass spectrometry, we identified the phospholipids,
      sphingolipids, and sterols present in Drosophila membranes. Despite chemical
      differences between Drosophila and mammalian lipids, their structure suggests
      that the biophysical properties that allow raft formation have been preserved.
      Consistent with this, we have identified a detergent-insoluble fraction of
      Drosophila membranes that, like mammalian rafts, is rich in sterol,
      sphingolipids, and glycosylphosphatidylinositol-linked proteins. We show that the
      sterol-linked Hedgehog N-terminal fragment associates specifically with this
      detergent-insoluble membrane fraction. Our findings demonstrate that raft
      formation is preserved across widely separated phyla in organisms with different
      lipid structures. They further suggest sterol modification as a novel mechanism
      for targeting proteins to raft membranes and raise the possibility that signaling
      and polarized intracellular transport of Hedgehog are based on raft association.

PMID- 10207029
TI  - Activation of guanine nucleotide-binding proteins and induction of endothelial
      tissue-type plasminogen activator gene transcription by alcohol.
AB  - The mechanism by which moderate alcohol ingestion lowers the risk of
      cardiovascular disease is unknown but may be due, in part, to the ability of
      alcohol to increase the level of tissue-type plasminogen activator (t-PA). Human
      endothelial cells were treated with low concentrations of ethanol (0.25-25 mM, 0
      24 h), which are associated with moderate alcohol consumption. Although treatment
      with ethanol alone did not affect t-PA gene transcription or mRNA expression, it
      augmented isoproterenol (ISO)-stimulated t-PA gene transcription and mRNA levels
      by 3.4- and 2.8-fold, respectively, and decreased plasminogen activator inhibitor
      1 mRNA levels by 65%. These effects of ethanol correlated with 2.5- and 6.9-fold
      increases in ISO-stimulated cyclic AMP levels and 4x-cyclic AMP response element
      heterologous promoter activity, respectively. To determine whether alcohol
      induced changes in agonist-stimulated cyclic AMP levels were because of
      modulation of guanine nucleotide-binding proteins (G proteins), we assessed the
      effects of ethanol on Galphas and Galphai2. Although ethanol did not affect the
      expression of Galphas or Galphai2, it increased ISO-stimulated Galphas GTPase and
      GTP binding activity by 2.2- and 2.9-fold and decreased UK14304-stimulated
      Galphai2 GTPase and GTP binding activity by 38 and 80%. These results indicate
      that treatment with relatively low concentrations of ethanol enhances agonist
      stimulated cyclic AMP-dependent t-PA gene transcription in vascular endothelial
      cells through differential modulation of G protein.

PMID- 10207030
TI  - Transcriptional activation of the human glutathione peroxidase promoter by p53.
AB  - Glutathione peroxidase (GPX) is a primary antioxidant enzyme that scavenges
      hydrogen peroxide or organic hydroperoxides. We have recently found that GPX is
      induced by etoposide, a topoisomerase II inhibitor and a p53 activator. In a
      search for a cis-element that confers potential p53 regulation of GPX, we
      identified a p53 binding site in the promoter of the GPX gene. This site bound to
      purified p53 as well as p53 in nuclear extract activated by etoposide. A
      luciferase reporter driven by a 262-base pair GPX promoter fragment was
      transcriptionally activated by wild type p53 in a p53 binding site-dependent
      manner. The same reporter was also activated in a p53 binding site-independent
      manner by several p53 mutants. The p53 binding and transactivation of the GPX
      promoter were enhanced by etoposide in p53-positive U2-OS cells. Etoposide
      induced transactivation was blocked by a dominant negative p53 mutant, indicating
      that endogenous wild type p53, upon activation by etoposide, transactivated the
      GPX promoter. Furthermore, expression of endogenous GPX was induced significantly
      at both mRNA and enzyme activity levels by etoposide in U2-OS cells but not in
      p53-negative Saos-2 cells. This is the first report demonstrating that GPX is a
      novel p53 target gene. The finding links the p53 tumor suppressor to an
      antioxidant enzyme and will facilitate study of the p53 signaling pathway and
      antioxidant enzyme regulation.

PMID- 10207031
TI  - Trypanosoma brucei RBP16 is a mitochondrial Y-box family protein with guide RNA
      binding activity.
AB  - Trypanosoma brucei mitochondria possess a unique mechanism of mRNA maturation
      called RNA editing. In this process, uridylate residues are inserted and deleted
      posttranscriptionally into pre-mRNA to create translatable messages. The genetic
      information for RNA editing resides in small RNA molecules called guide RNAs
      (gRNAs). Thus, proteins in direct contact with gRNA are likely to catalyze or
      influence RNA editing. Herein we characterize an abundant gRNA-binding protein
      from T. brucei mitochondria. This protein, which we term RBP16 (for RNA-binding
      protein of 16 kDa), binds to different gRNA molecules. The major determinant of
      this interaction is the oligo(U) tail, present on the 3'-ends of gRNAs. RBP16
      forms multiple, stable complexes with gRNA in vitro, and immunoprecipitation
      experiments provide evidence for an association between RBP16 and gRNA within T.
      brucei mitochondria. Mature RBP16 contains a cold shock domain at the N terminus
      and a C-terminal region rich in arginine and glycine. The presence of the cold
      shock domain places RBP16 as the first organellar member of the highly conserved
      Y-box protein family. The arginine and glycine rich C terminus in combination
      with the cold shock domain predicts that RBP16 will be involved in the regulation
      of gene expression at the posttranscriptional level.

PMID- 10207033
TI  - Thermotolerant cells show an attenuated expression of Hsp70 after heat shock.
AB  - Expression of heat shock proteins (hsps) results in the protection of cells from
      subsequent stresses. However, hsps are also toxic when present within cells for a
      prolonged time period. Thus, the expression of hsps should be tightly regulated.
      In the present study, the expression of Hsp70 after heat shock was compared
      between thermotolerant cells, which contain a large concentration of Hsp70, and
      nonthermotolerant cells (naive). Accumulation of Hsp70, assessed by Western
      blotting, was negligible when thermotolerant cells were heat-shocked a second
      time. Hsp70 transcription was similar between thermotolerant and naive cells
      during heat shock. However, Hsp70 transcription was attenuated more rapidly in
      thermotolerant than naive cells immediately upon return to non-heat shock
      conditions. In addition, Hsp70 mRNA stability was reduced in thermotolerant cells
      as compared with naive cells following the stress. New synthesis of Hsp70 and the
      efficiency of Hsp70 mRNA translation were similar between thermotolerant and
      naive cells during the post-stress period. These results suggest that
      thermotolerant cells limit Hsp70 expression by transcriptional and
      pretranslational mechanisms, perhaps to avoid the potential cytotoxic effect of
      these proteins.

PMID- 10207034
TI  - U50,488H-induced internalization of the human kappa opioid receptor involves a
      beta-arrestin- and dynamin-dependent mechanism. Kappa receptor internalization is
      not required for mitogen-activated protein kinase activation.
AB  - Agonist-promoted internalization of some G protein-coupled receptors has been
      shown to mediate receptor desensitization, resensitization, and down-regulation.
      In this study, we investigated whether opioids induced internalization of the
      human and rat kappa opioid receptors stably expressed in Chinese hamster ovary
      cells, the potential mechanisms involved in this process and its possible role in
      activation of mitogen-activated protein (MAP) kinase. Exposure of the human kappa
      receptor to the agonists U50,488H, U69,593, ethylketocyclazocine, or tifluadom,
      but not etorphine, promoted receptor internalization. However, none of these
      agonists induced significant internalization of the rat kappa opioid receptor.
      U50, 488H-induced human kappa receptor internalization was time- and
      concentration-dependent, with 30-40% of the receptors internalized following a 30
      min exposure to 1 microM U50,488H. Agonist removal resulted in the receptors
      gradually returning to the cell surface over a 60-min period. The antagonist
      naloxone blocked U50, 488H-induced internalization without affecting
      internalization itself, while pretreatment with pertussis toxin had no effect on
      U50, 488H-induced internalization. In contrast, incubation with sucrose (0.4-0.8
      M) significantly reduced U50,488H-induced internalization of the kappa receptor.
      While co-expression of the wild type GRK2, beta-arrestin, or dynamin I had no
      effect on kappa receptor internalization, co-expression of the dominant negative
      mutants GRK2-K220R, beta-arrestin (319-418), or dynamin I-K44A significantly
      inhibited receptor internalization. Whether receptor internalization is critical
      for MAP kinase activation was next investigated. Co-expression of dominant
      negative mutants of beta-arrestin or dynamin I, which greatly reduced U50,488H
      induced internalization, did not affect MAP kinase activation by the agonist. In
      addition, etorphine, which did not promote human kappa receptor internalization,
      was able to fully activate MAP kinase. Moreover, U50,488H or etorphine
      stimulation of the rat kappa receptor, which did not undergo internalization,
      also effectively activated MAP kinase. Thus, U50,488H-induced internalization of
      the human kappa opioid receptor in Chinese hamster ovary cells occurs via a GRK-,
      beta-arrestin-, and dynamin I-dependent process that likely involves clathrin
      coated pits. In addition, internalization of the kappa receptor is not required
      for activation of MAP kinase.

PMID- 10207032
TI  - Mutation of tyrosine 960 within the insulin receptor juxtamembrane domain impairs
      glucose transport but does not inhibit ligand-mediated phosphorylation of insulin
      receptor substrate-2 in 3T3-L1 adipocytes.
AB  - CSF-1 is equipotent to insulin in its ability to stimulate 2-[3H]deoxyglucose
      uptake in 3T3-L1 adipocytes expressing the colony stimulating factor-1
      receptor/insulin receptor chimera (CSF1R/IR). However, CSF-1-stimulated glucose
      uptake and glycogen synthesis is reduced by 50% in comparison to insulin in 3T3
      L1 cells expressing a CSF1R/IR mutated at Tyr960 (CSF1R/IRA960). CSF-1-treated
      adipocytes expressing the CSF1R/IRA960 were impaired in their ability to
      phosphorylate insulin receptor substrate 1 (IRS-1) but not in their ability to
      phosphorylate IRS-2. Immunoprecipitation of IRS proteins followed by Western
      blotting revealed that the intact CSF1R/IR co-precipitates with IRS-2 from CSF-1
      treated cells. In contrast, the CSF1R/IRA960 co-precipitates poorly with IRS-2.
      These observations suggest that Tyr960 is important for interaction of the
      insulin receptor cytoplasmic domain with IRS-2, but it is not essential to the
      ability of the insulin receptor tyrosine kinase to use IRS-2 as a substrate.
      These observations also suggest that in 3T3-L1 adipocytes, tyrosine
      phosphorylation of IRS-2 by the insulin receptor tyrosine kinase is not
      sufficient for maximal stimulation of receptor-regulated glucose transport or
      glycogen synthesis.

PMID- 10207036
TI  - Overproduction and characterization of the Bacillus subtilis anti-sigma factor
      FlgM.
AB  - FlgM is an anti-sigma factor of the flagellar-specific sigma (sigma) subunit of
      RNA polymerase in Bacillus subtilis, and it is responsible of the coupling of
      late flagellar gene expression to the completion of the hook-basal body
      structure. We have overproduced the protein in soluble form and characterized it.
      FlgM forms dimers as shown by gel exclusion chromatography and native
      polyacrylamide gel electrophoresis and interacts in vitro with the cognate sigmaD
      factor. The FlgM.sigmaD complex is a stable heterodimer as demonstrated by gel
      exclusion chromatography, chemical cross-linking, native polyacrylamide gel
      electrophoresis, and isoelectric focusing. sigmaD belongs to the group of sigma
      factors able to bind to the promoter sequence even in the absence of core RNA
      polymerase. The FlgM.sigmaD complex gave a shift in a DNA mobility shift assay
      with a probe containing a sigmaD-dependent promoter sequence. Limited proteolysis
      studies indicate the presence of two structural motifs, corresponding to the N-
      and C-terminal regions, respectively.

PMID- 10207035
TI  - The CACC box and myocyte enhancer factor-2 sites within the myosin light chain 2
      slow promoter cooperate in regulating nerve-specific transcription in skeletal
      muscle.
AB  - Previous experiments showed that activity of the -800-base pair MLC2slow promoter
      was 75-fold higher in the innervated soleus (SOL) compared with the noninnervated
      SOL muscles. Using in vivo DNA injection of MLC2slow promoter-luciferase
      constructs, the aim of this project was to identify regulatory sites and
      potential transcription factors important for slow nerve-dependent gene
      expression. Three sites within the proximal promoter (myocyte enhancer factor-2
      (MEF2), E-box, and CACC box) were individually mutated, and the effect on
      luciferase expression was determined. There was no change in luciferase
      expression in the SOL and extensor digitorum longus (EDL) muscles when the E-box
      was mutated. In contrast, the MEF2 mutation resulted in a 30-fold decrease in
      expression in the innervated SOL muscles (10.3 versus 0.36 normalized relative
      light units (RLUs)). Transactivation of the MLC2slow promoter by overexpressing
      MEF2 was only seen in the innervated SOL (676,340 versus 2,225,957 RLUs; p <
      0.01) with no effect in noninnervated SOL or EDL muscles. These findings suggest
      that the active MLC2slow promoter is sensitive to MEF2 levels, but MEF2 levels
      alone do not determine nerve-dependent expression. Mutation of the CACC box
      resulted in a significant up-regulation in the EDL muscles (0.23 versus 4.08
      normalized RLUs). With the CACC box mutated, overexpression of MEF2 was
      sufficient to transactivate the MLC2slow promoter in noninnervated SOL muscles
      (27,536 versus 1, 605,797 RLUs). Results from electrophoretic mobility shift and
      supershift assays confirm MEF2 protein binding to the MEF2 site and demonstrate
      specific binding to the CACC sequence. These results suggest a model for nerve
      dependent regulation of the MLC2slow promoter in which derepression occurs
      through the CACC box followed by quantitative expression through enhanced MEF2
      activation.

PMID- 10207037
TI  - Cloning and characterization of the 5'-flanking region of the human growth
      hormone-releasing hormone receptor gene.
AB  - We cloned the 5'-flanking region of the human growth hormone-releasing hormone
      receptor (GHRH-R) gene and determined the nucleotide sequence of 2.7 kilobases
      upstream from the translation start site. RNase protection analysis showed the
      major transcription start site is 122 base pairs upstream from the translation
      start site. The 5'-end of the longest product of 5'-rapid amplification of cDNA
      ends was close to the site. There were no typical TATA homologies but several
      putative regulatory elements including Pit-1-binding site-like element. Transient
      transfection studies using a luciferase reporter gene demonstrated that 5'
      flanking region had promoter activity in GH3 cells (derived from rat pituitary
      tumor) but not in nonpituitary cells, BeWo and HeLa cells. However, co
      transfection of Pit-1 expression vector increased luciferase activity in BeWo
      cells. Deletion study showed that the regions from -310 to -130 and from -130 to 
      120 were important for the GHRH-R gene expression in GH3 cells, although the
      latter contributed less to the gene expression. In BeWo cells co-transfected with
      Pit-1 expression vector, the region from -310 to -130 was essential for the Pit-1
      dependent expression of GHRH-R gene. The region from -310 to -120 has two
      putative Pit-1-binding sites, P1 and P2, located from -129 to -123 and from -171
      to -160, respectively. Both mobility shift assay and DNase-I footprint analysis
      showed that P2 had much higher Pit-1 binding affinity than P1. Mutation of P2
      decreased GHRH-R gene expression in GH3 cells. These findings were consistent
      with the results that the region from -310 to -130 is an important element for
      Pit-1-dependent expression of GHRH-R gene.

PMID- 10207038
TI  - Cross-talk between the aryl hydrocarbon receptor and hypoxia inducible factor
      signaling pathways. Demonstration of competition and compensation.
AB  - The aryl hydrocarbon receptor (AHR) and the alpha-class hypoxia inducible factors
      (HIF1alpha, HIF2alpha, and HIF3alpha) are basic helix-loop-helix PAS (bHLH-PAS)
      proteins that heterodimerize with ARNT. In response to 2,3,7,8-tetrachlorodibenzo
      p-dioxin, the AHR. ARNT complex binds to "dioxin responsive enhancers" (DREs) and
      activates genes involved in the metabolism of xenobiotics, e.g. cytochrome
      P4501A1 (Cyp1a1). The HIF1alpha.ARNT complex binds to "hypoxia responsive
      enhancers" and activates the transcription of genes that regulate adaptation to
      low oxygen, e.g. erythropoietin (Epo). We postulated that activation of one
      pathway would inhibit the other due to competition for ARNT or other limiting
      cellular factors. Using pathway specific reporters in transient transfection
      assays, we observed that DRE driven transcription was markedly inhibited by
      hypoxia and that hypoxia responsive enhancer driven transcription was inhibited
      by AHR agonists. When we attempted to support this cross-talk model using
      endogenous loci, we observed that activation of the hypoxia pathway inhibited
      Cyp1a1 up-regulation, but that activation of the AHR actually enhanced the
      induction of Epo by hypoxia. To explain this unexpected additivity, we examined
      the Epo gene and found that its promoter harbors DREs immediately upstream of its
      transcriptional start site. These experiments outline conditions where inhibitory
      and additive cross-talk occur between the hypoxia and dioxin signal transduction
      pathways and identify Epo as an AHR-regulated gene.

PMID- 10207039
TI  - Phosphorylation of F-actin-associating G protein gamma12 subunit enhances
      fibroblast motility.
AB  - Eleven isoforms of G protein gamma subunit have been found thus far, but the
      precise roles of individual gamma subunits are not known. The gamma12 subunit has
      two unique properties: phosphorylation by protein kinase C and association with F
      actin. To elucidate the role of gamma12, we overexpressed gamma12 and other gamma
      subunits in NIH 3T3 cells together with the beta1 subunit. The overexpressed
      gamma12 as well as endogenous gamma12, but not gamma2, gamma5, and gamma7
      subunits, associated with cytoskeletal components. Expression of gamma12 induced
      remarkable changes including cell rounding, disruption of stress fibers, and
      enhancement of cell migration, but expression of other gamma subunits did not
      induce significant changes. Deletion of the N-terminal region of gamma12
      decreased the abilities of gamma12 to associate with cytoskeletal fractions, to
      induce cell rounding, and to increase cell motility. Replacement by alanine of
      Ser2 of gamma12 (Ser1 of a mature gamma12 protein), a phosphorylation site for
      protein kinase C, eliminated these effects of gamma12, whereas a mutant in which
      Ser2 was replaced with glutamic acid showed effects equivalent to wild-type
      gamma12. These results indicate that phosphorylation of gamma12 at Ser2 enhances
      the motility of cells.

PMID- 10207040
TI  - Regulation of Dictyostelium protein-tyrosine phosphatase-3 (PTP3) through osmotic
      shock and stress stimulation and identification of pp130 as a PTP3 substrate.
AB  - Osmotic shock and growth-medium stimulation of Dictyostelium cells results in
      rapid cell rounding, a reduction in cell volume, and a rearrangement of the
      cytoskeleton that leads to resistance to osmotic shock. Osmotic shock induces the
      activation of guanylyl cyclase, a rise in cGMP mediating the phosphorylation of
      myosin II, and the tyrosine phosphorylation of actin and the approximately 130
      kDa protein (p130). We present data suggesting that signaling pathways leading to
      these different responses are, at least in part, independent. We show that a
      variety of stresses induce the Ser/Thr phosphorylation of the protein-tyrosine
      phosphatase-3 (PTP3). This modification does not alter PTP3 catalytic activity
      but correlates with its translocation from the cytosol to subcellular structures
      that co-localize to endosomal vesicles. This translocation is independent of PTP3
      activity. Mutation of the catalytically essential Cys to a Ser results in
      inactive PTP3 that forms a stable complex with tyrosine-phosphorylated p130
      (pp130) in vivo and in vitro, suggesting that PTP3 has a substrate specificity
      for pp130. The data suggest that stresses activate several interacting signaling
      pathways controlled by Ser/Thr and Tyr phosphorylation, which, along with the
      activation of guanylyl cyclase, mediate the ability of this organism to respond
      to adverse changes in the external environment.

PMID- 10207041
TI  - Interferon-gamma-mediated inhibition of cyclin A gene transcription is
      independent of individual cis-acting elements in the cyclin A promoter.
AB  - Interferons (IFNs) affect cellular functions by altering gene expression. The
      eukaryotic cell cycle is governed in part by the periodic transcription of cyclin
      genes, whose protein products associate with and positively regulate the cyclin
      dependent kinases. To understand better the growth inhibitory effect of IFN-gamma
      on vascular smooth muscle cells (VSMCs), we compared the expression and activity
      of G1 and S phase cyclins in control and IFN-gamma-treated VSMCs. IFN-gamma
      treatment did not inhibit the G1 cyclins but did decrease cyclin A protein, mRNA,
      and associated kinase activity by 85, 90, and 90%, respectively. Nuclear run-on
      and mRNA stability determinations indicated that this decrease was the result of
      transcriptional inhibition. To investigate the molecular basis of this
      inhibition, we examined protein-DNA interactions involving the cyclin A promoter.
      Electromobility shift assays showed little change with IFN-gamma treatment in the
      binding of nuclear proteins to isolated ATF, NF-Y, and CDE elements. In vivo
      genomic footprinting indicated that IFN-gamma treatment changed the occupancy of
      chromosomal NF-Y and CDE sites slightly and did not affect occupancy of the ATF
      site. In a previous study of transforming growth factor-beta1-mediated inhibition
      of the cyclin A promoter, we mapped the inhibitory effect to the ATF site; in the
      present study of IFN-gamma treatment, functional analysis by transient
      transfection showed that inhibition of the cyclin A promoter persisted despite
      mutation of the ATF, NF-Y, or CDE elements. We hypothesize that IFN-gamma
      inhibits cyclin A transcription by modifying co-activators or general
      transcription factors within the complex that drives transcription of the cyclin
      A gene.

PMID- 10207043
TI  - Modulation of inositol 1,4,5-trisphosphate binding to the recombinant ligand
      binding site of the type-1 inositol 1,4, 5-trisphosphate receptor by Ca2+ and
      calmodulin.
AB  - A recombinant protein (Lbs-1) containing the N-terminal 581 amino acids of the
      mouse type 1 inositol 1,4,5-trisphosphate receptor (IP3R-1), including the
      complete IP3-binding site, was expressed in the soluble fraction of E. coli. The
      characteristics of IP3 binding to this protein were similar as observed
      previously for the intact IP3R-1. Ca2+ dose-dependently inhibited IP3 binding to
      Lbs-1 with an IC50 of about 200 nM. This effect represented a decrease in the
      affinity of Lbs-1 for IP3, because the Kd increased from 115 +/- 15 nM in the
      absence to 196 +/- 18 nM in the presence of 5 microM Ca2+. The maximal effect of
      Ca2+ on Lbs-1 (5 microM Ca2+, 42.0 +/- 6.4% inhibition) was similar to the
      maximal inhibition observed for microsomes of insect Sf9 cells expressing full
      length IP3R-1 (33.8 +/- 10.2%). Conceivably, the two contiguous Ca2+-binding
      sites (residues 304-450 of mouse IP3R-1) previously found by us (Sienaert, I.,
      Missiaen, L., De Smedt, H., Parys, J.B., Sipma, H., and Casteels, R. (1997) J.
      Biol. Chem. 272, 25899-25906) mediate the effect of Ca2+ on IP3 binding to IP3R
      1. Calmodulin also dose-dependently inhibited IP3 binding to Lbs-1 with an IC50
      of about 3 microM. Maximal inhibition (10 microM calmodulin, 43.1 +/- 5.9%) was
      similar as observed for Sf9-IP3R-1 microsomes (35.8 +/- 8.7%). Inhibition by
      calmodulin occurred independently of Ca2+ and was additive to the inhibitory
      effect of 5 microM Ca2+ (together 74.5 +/- 5.1%). These results suggest that the
      N-terminal ligand-binding region of IP3R-1 contains a calmodulin-binding domain
      that binds calmodulin independently of Ca2+ and that mediates the inhibition of
      IP3 binding to IP3R-1.

PMID- 10207042
TI  - Modular variations of the human major histocompatibility complex class III genes
      for serine/threonine kinase RP, complement component C4, steroid 21-hydroxylase
      CYP21, and tenascin TNX (the RCCX module). A mechanism for gene deletions and
      disease associations.
AB  - The frequent variations of human complement component C4 gene size and gene
      numbers, plus the extensive polymorphism of the proteins, render C4 an excellent
      marker for major histocompatibility complex disease associations. As shown by
      definitive RFLPs, the tandemly arranged genes RP, C4, CYP21, and TNX are
      duplicated together as a discrete genetic unit termed the RCCX module.
      Duplications of the RCCX modules occurred by the addition of genomic fragments
      containing a long (L) or a short (S) C4 gene, a CYP21A or a CYP21B gene, and the
      gene fragments TNXA and RP2. Four major RCCX structures with bimodular L-L,
      bimodular L-S, monomodular L, and monomodular S are present in the Caucasian
      population. These modules are readily detectable by TaqI RFLPs. The RCCX modular
      variations appear to be a root cause for the acquisition of deleterious mutations
      from pseudogenes or gene segments in the RCCX to their corresponding functional
      genes. In a patient with congenital adrenal hyperplasia, we discovered a TNXB
      TNXA recombinant with the deletion of RP2-C4B-CYP21B. Elucidation of the DNA
      sequence for the recombination breakpoint region and sequence analyses yielded
      definitive proof for an unequal crossover between TNXA from a bimodular
      chromosome and TNXB from a monomodular chromosome.

PMID- 10207044
TI  - Identification of two Smad4 proteins in Xenopus. Their common and distinct
      properties.
AB  - Smad family proteins have been identified as mediators of intracellular signal
      transduction by the transforming growth factor-beta (TGF-beta) superfamily. Each
      member of the pathway-restricted, receptor-activated Smad family cooperates and
      synergizes with Smad4, called co-Smad, to transduce the signals. Only Smad4 has
      been shown able to function as a common partner of the various pathway-restricted
      Smads in mammals. Here we have identified a novel Smad4-like molecule in Xenopus
      (XSmad4beta) as well as a Xenopus homolog of a well established Smad4
      (XSmad4alpha). XSmad4beta is 70% identical to XSmad4alpha in amino acid sequence.
      Both of the Xenopus Smad4s can cooperate with Smad1 and Smad2, the pathway
      restricted Smads specific for bone morphogenetic protein and TGF-beta,
      respectively. However, they show distinct properties in terms of their
      developmental expression patterns, subcellular localizations, and phosphorylation
      states. Moreover, XSmad4beta, but not XSmad4alpha, has the potent ability to
      induce ventralization when microinjected into the dorsal marginal region of the 4
      cell stage of the embryos. These results suggest that the two Xenopus Smad4s have
      overlapping but distinct functions.

PMID- 10207045
TI  - Dual specificity protein kinase activity of testis-specific protein kinase 1 and
      its regulation by autophosphorylation of serine-215 within the activation loop.
AB  - TESK1 (testis-specific protein kinase 1) is a protein kinase with a structure
      composed of an N-terminal protein kinase domain and a C-terminal proline-rich
      domain. Whereas the 3.6-kilobase TESK1 mRNA is expressed predominantly in the
      testis, a faint 2.5-kilobase TESK1 mRNA is expressed ubiquitously. The kinase
      domain of TESK1 contains in the catalytic loop in subdomain VIB an unusual DLTSKN
      sequence, which is not related to the consensus sequence of either
      serine/threonine kinases or tyrosine kinases. In this study, we show that TESK1
      has kinase activity with dual specificity on both serine/threonine and tyrosine
      residues. In an in vitro kinase reaction, the kinase domain of TESK1 underwent
      autophosphorylation on serine and tyrosine residues and catalyzed phosphorylation
      of histone H3 and myelin basic protein on serine, threonine, and tyrosine
      residues. Site-directed mutagenesis analyses revealed that Ser-215 within the
      "activation loop" of the kinase domain is the site of serine autophosphorylation
      of TESK1. Replacement of Ser-215 by alanine almost completely abolished serine
      autophosphorylation and histone H3 kinase activities. In contrast, replacement of
      Ser-215 by glutamic acid abolished serine autophosphorylation activity but
      retained histone H3 kinase activity. These results suggest that
      autophosphorylation of Ser-215 is an important step to positively regulate the
      kinase activity of TESK1.

PMID- 10207046
TI  - Chloroplast SecY is complexed to SecE and involved in the translocation of the 33
      kDa but not the 23-kDa subunit of the oxygen-evolving complex.
AB  - SecY is a component of the protein-conducting channel for protein transport
      across the cytoplasmic membrane of prokaryotes. It is intimately associated with
      a second integral membrane protein, SecE, and together with SecA forms the
      minimal core of the preprotein translocase. A chloroplast homologue of SecY
      (cpSecY) has previously been identified and determined to be localized to the
      thylakoid membrane. In the present work, we demonstrate that a SecE homologue is
      localized to the thylakoid membrane, where it forms a complex with cpSecY.
      Digitonin solubilization of thylakoid membranes releases the SecY/E complex in a
      180-kDa form, indicating that other components are present and/or the complex is
      a higher order oligomer of the cpSecY/E dimer. To test whether cpSecY forms the
      protein-conducting channel of the thylakoid membrane, translocation assays were
      conducted with the SecA-dependent substrate OE33 and the SecA-independent
      substrate OE23, in the presence and absence of antibodies raised against cpSecY.
      The antibodies inhibited translocation of OE33 but not OE23, indicating that
      cpSecY comprises the protein-conducting channel used in the SecA-dependent
      pathway, whereas a distinct protein conducting channel is used to translocate
      OE23.

PMID- 10207047
TI  - The src homology domain 2-containing inositol phosphatase SHIP forms a ternary
      complex with Shc and Grb2 in antigen receptor-stimulated B lymphocytes.
AB  - The inositol phosphatase SHIP has been implicated in signaling events downstream
      of a variety of receptors and is thought to play an inhibitory role in stimulated
      B cells. We and others have reported that SHIP is rapidly tyrosine phosphorylated
      upon B cell antigen receptor (BCR) cross-linking and forms a complex with the
      adapter protein Shc. Here, we report that cross-linking of the BCR induces
      association between Grb2 and SHIP as well as association between Shc and SHIP. We
      made use of a Grb2-deficient B cell line to demonstrate both in vitro and in vivo
      that Grb2 expression is required for the efficient association between Shc and
      SHIP. The results indicate that SHIP, Shc, and Grb2 form a ternary complex in
      stimulated B cells, with Grb2 stabilizing the interaction between Shc and SHIP.
      The interactions between Shc, Grb2, and SHIP are therefore analogous to the
      interactions between Shc, Grb2, and SOS. Shc and Grb2 may help to localize SHIP
      to the cell membrane, regulating SHIP's inhibitory function following BCR
      stimulation.

PMID- 10207048
TI  - AT-AC pre-mRNA splicing mechanisms and conservation of minor introns in voltage
      gated ion channel genes.

PMID- 10207049
TI  - Glycogen synthase phosphatase interacts with heat shock factor to activate CUP1
      gene transcription in Saccharomyces cerevisiae.
AB  - Upon heat shock, transcription of many stress-inducible genes is rapidly and
      dramatically stimulated by heat shock factor (HSF). A central region of the yeast
      HSF (designated HSFrr for "repression region") was previously identified and
      proposed to be involved in repressing the activation domain under non-heat-shock
      conditions. Here, we used the phage display system to isolate proteins that
      interact with HSFrr. This should identify factors that modulate HSF activity or
      directly participate in HSF-mediated transcriptional activation. We constructed a
      randomly sheared yeast genomic library to express yeast proteins on the surface
      of lambda phage. HSFrr binding phages were selected by cycles of affinity
      chromatography. DNA sequencing identified an HSFrr-interacting phage that
      contains the GAC1 gene. The GAC1 gene encodes the regulatory subunit for a type 1
      serine/threonine phosphoprotein phosphatase, Glc7. Both gac1 and glc7 mutations
      had little effect on HSF activation of gene transcription of two heat shock
      genes, SSA4 and HSP82. In contrast, heat shock induction of CUP1 gene expression
      was completely abolished in a glc7 mutant and reduced in a gac1 mutant. The
      results demonstrate that the Glc7 phosphatase and its Gac1 regulatory subunit
      play positive roles in HSF activation of CUP1 transcription.

PMID- 10207051
TI  - MDM2 suppresses p73 function without promoting p73 degradation.
AB  - The newly identified p53 homolog p73 can mimic the transcriptional activation
      function of p53. We investigated whether p73, like p53, participates in an
      autoregulatory feedback loop with MDM2. p73 bound to MDM2 both in vivo and in
      vitro. Wild-type but not mutant MDM2, expressed in human p53 null osteosarcoma
      Saos-2 cells, inhibited p73- and p53-dependent transcription driven by the MDM2
      promoter-derived p53RE motif as measured in transient-transfection and
      chloramphenicol acetyltransferase assays and also inhibited p73-induced apoptosis
      in p53-null human lung adenocarcinoma H1299 cells. MDM2 did not promote the
      degradation of p73 but instead disrupted the interaction of p73, but not of p53,
      with p300/CBP by competing with p73 for binding to the p300/CBP N terminus. Both
      p73alpha and p73beta stimulated the expression of the endogenous MDM2 protein.
      Hence, MDM2 is transcriptionally activated by p73 and, in turn, negatively
      regulates the function of this activator through a mechanism distinct from that
      used for p53 inactivation.

PMID- 10207050
TI  - Cumulative effect of phosphorylation of pRB on regulation of E2F activity.
AB  - The product of the retinoblastoma susceptibility gene, pRB, is a nuclear
      phosphoprotein that controls cell growth by binding to and suppressing the
      activities of transcription factors such as the E2F family. Transactivation
      activity is inhibited when E2F is bound to hypophosphorylated pRB and released
      when pRB is phosphorylated by cyclin-dependent kinases (CDKs). To determine which
      of 16 potential CDK phosphorylation sites regulated the pRB-E2F interaction,
      mutant pRB proteins produced by site-directed mutagenesis were tested for the
      ability to suppress E2F-mediated transcription in a reporter chloramphenicol
      acetyltransferase assay. Surprisingly, no one CDK site regulated the interaction
      of pRB with E2F when E2F was bound to DNA. Instead, disruption of transcriptional
      repression resulted from accumulation of phosphate groups on the RB molecule.

PMID- 10207052
TI  - The C terminus of Ku80 activates the DNA-dependent protein kinase catalytic
      subunit.
AB  - Ku is a heterodimeric protein with double-stranded DNA end-binding activity that
      operates in the process of nonhomologous end joining. Ku is thought to target the
      DNA-dependent protein kinase (DNA-PK) complex to the DNA and, when DNA bound, can
      interact and activate the DNA-PK catalytic subunit (DNA-PKcs). We have carried
      out a 3' deletion analysis of Ku80, the larger subunit of Ku, and shown that the
      C-terminal 178 amino acid residues are dispensable for DNA end-binding activity
      but are required for efficient interaction of Ku with DNA-PKcs. Cells expressing
      Ku80 proteins that lack the terminal 178 residues have low DNA-PK activity, are
      radiation sensitive, and can recombine the signal junctions but not the coding
      junctions during V(D)J recombination. These cells have therefore acquired the
      phenotype of mouse SCID cells despite expressing DNA-PKcs protein, suggesting
      that an interaction between DNA-PKcs and Ku, involving the C-terminal region of
      Ku80, is required for DNA double-strand break rejoining and coding but not signal
      joint formation. To gain further insight into important domains in Ku80, we
      report a point mutational change in Ku80 in the defective xrs-2 cell line. This
      residue is conserved among species and lies outside of the previously reported
      Ku70-Ku80 interaction domain. The mutational change nonetheless abrogates the
      Ku70-Ku80 interaction and DNA end-binding activity.

PMID- 10207053
TI  - Insulin receptor isoform A, a newly recognized, high-affinity insulin-like growth
      factor II receptor in fetal and cancer cells.
AB  - Insulin-like growth factor II (IGF-II) is a peptide growth factor that is
      homologous to both insulin-like growth factor I (IGF-I) and insulin and plays an
      important role in embryonic development and carcinogenesis. IGF-II is believed to
      mediate its cellular signaling via the transmembrane tyrosine kinase type 1
      insulin-like growth factor receptor (IGF-I-R), which is also the receptor for IGF
      I. Earlier studies with both cultured cells and transgenic mice, however, have
      suggested that in the embryo the insulin receptor (IR) may also be a receptor for
      IGF-II. In most cells and tissues, IR binds IGF-II with relatively low affinity.
      The IR is expressed in two isoforms (IR-A and IR-B) differing by 12 amino acids
      due to the alternative splicing of exon 11. In the present study we found that IR
      A but not IR-B bound IGF-II with an affinity close to that of insulin. Moreover,
      IGF-II bound to IR-A with an affinity equal to that of IGF-II binding to the IGF
      I-R. Activation of IR-A by insulin led primarily to metabolic effects, whereas
      activation of IR-A by IGF-II led primarily to mitogenic effects. These
      differences in the biological effects of IR-A when activated by either IGF-II or
      insulin were associated with differential recruitment and activation of
      intracellular substrates. IR-A was preferentially expressed in fetal cells such
      as fetal fibroblasts, muscle, liver and kidney and had a relatively increased
      proportion of isoform A. IR-A expression was also increased in several tumors
      including those of the breast and colon. These data indicate, therefore, that
      there are two receptors for IGF-II, both IGF-I-R and IR-A. Further, they suggest
      that interaction of IGF-II with IR-A may play a role both in fetal growth and
      cancer biology.

PMID- 10207054
TI  - Ubiquitination and degradation of ATF2 are dimerization dependent.
AB  - Ubiquitination and proteasome-dependent degradation are key determinants of the
      half-lives of many transcription factors. Homo- or heterodimerization of basic
      region-leucine zipper (bZIP) transcription factors is required for their
      transcriptional activities. Here we show that activating transcription factor 2
      (ATF2) heterodimerization with specific bZIP proteins is an important determinant
      of the ubiquitination and proteasome-dependent degradation of ATF2. Depletion of
      c-Jun as one of the ATF2 heterodimer partners from the targeting proteins
      decreased the efficiency of ATF2 ubiquitination in vitro, whereas the addition of
      exogenously purified c-Jun restored it. Similarly, overexpression of c-Jun in
      293T human embryo kidney cells increased ATF2 ubiquitination in vivo and reduced
      its half-life in a dose-dependent manner. Mutations of ATF2 that disrupt its
      dimerization inhibited ATF2 ubiquitination in vitro and in vivo. Conversely,
      removal of residues 150 to 248, as in a constitutively active ATF2 spliced form,
      enhanced ATF2 dimerization and transactivation, which coincided with increased
      ubiquitination and decreased stability. Our findings indicate the increased
      sensitivity of transcriptionally active dimers of ATF2 to ubiquitination and
      proteasome-dependent degradation. Based on these observations, we conclude that
      increased targeting of a transcriptionally active ATF2 form indicates the
      mechanism by which the magnitude and the duration of the cellular stress response
      are regulated.

PMID- 10207055
TI  - Uncouplers of oxidative phosphorylation can enhance a Fas death signal.
AB  - Recent work suggests a participation of mitochondria in apoptotic cell death.
      This role includes the release of apoptogenic molecules into the cytosol
      preceding or after a loss of mitochondrial membrane potential DeltaPsim. The two
      uncouplers of oxidative phosphorylation carbonyl cyanide m-chlorophenylhydrazone
      (CCCP) and 2, 4-dinitrophenol (DNP) reduce DeltaPsim by direct attack of the
      proton gradient across the inner mitochondrial membrane. Here we show that both
      compounds enhance the apoptosis-inducing capacity of Fas/APO-1/CD95 signaling in
      Jurkat and CEM cells without causing apoptotic changes on their own account. This
      amplification occurred upstream or at the level of caspases and was not inhibited
      by Bcl-2. The effect could be blocked by the cowpox protein CrmA and is thus
      likely to require caspase 8 activity. Apoptosis induction by staurosporine in
      Jurkat cells as well as by Fas in SKW6 cells was unaffected by CCCP and DNP. The
      role of cytochrome c during Fas-DNP signaling was investigated. No early
      cytochrome c release from mitochondria was detected by Western blotting.
      Functional assays with cytoplasmic preparations from Fas-DNP-treated cells also
      indicated that there was no major contribution by cytochrome c or caspase 9 to
      the activation of effector caspases. Furthermore, an increase of rhodamine-123
      uptake into intact cells, which has been explained by mitochondrial swelling,
      occurred considerably later than the caspase activation and was blocked by Z-VAD
      fmk. These data show that uncouplers of oxidative phosphorylation can
      presensitize some but not all cells for a Fas death signal and provide
      information about the existence of separate pathways in the induction of
      apoptosis.

PMID- 10207056
TI  - NDD1, a high-dosage suppressor of cdc28-1N, is essential for expression of a
      subset of late-S-phase-specific genes in Saccharomyces cerevisiae.
AB  - cdc28-1N mutants progress through the G1 and S phases normally at the restrictive
      temperature but fail to undergo nuclear division. We have isolated a gene, NDD1,
      which at a high dosage suppresses the nuclear-division defect of cdc28-1N. NDD1
      (nuclear division defective) is an essential gene. Its expression during the cell
      cycle is tightly regulated such that NDD1 RNA is most abundant during the S
      phase. Cells lacking the NDD1 gene arrest with an elongated bud, a short mitotic
      spindle, 2N DNA content, and an undivided nucleus, suggesting that its function
      is required for some aspect of nuclear division. We show that overexpression of
      Ndd1 results in the upregulation of both CLB1 and CLB2 transcription, suggesting
      that the suppression of cdc28-1N by NDD1 may be due to an accumulation of these
      cyclins. Overproduction of Ndd1 also enhances the expression of SWI5, whose
      transcription, like that of CLB1 and CLB2, is activated in the late S phase. Ndd1
      is essential for the expression of CLB1, CLB2, and SWI5, since none of these
      genes are transcribed in its absence. Both CLB2 expression and its upregulation
      by NDD1 are mediated by a 240-bp promoter sequence that contains four MCM1
      binding sites. However, Ndd1 does not appear to be a component of any of the
      protein complexes assembled on this DNA fragment, as indicated by gel mobility
      shift assays. Instead, overexpression of NDD1 prevents the formation of one of
      the complexes whose appearance correlates with the termination of CLB2 expression
      in G1. The inability of GAL1 promoter-driven CLB2 to suppress the lethality of
      NDD1 null mutant suggests that, in addition to CLB1 and CLB2, NDD1 may also be
      required for the transcription of other genes whose functions are necessary for
      G2/M transition.

PMID- 10207057
TI  - A novel mechanism of ion homeostasis and salt tolerance in yeast: the Hal4 and
      Hal5 protein kinases modulate the Trk1-Trk2 potassium transporter.
AB  - The regulation of intracellular ion concentrations is a fundamental property of
      living cells. Although many ion transporters have been identified, the systems
      that modulate their activity remain largely unknown. We have characterized two
      partially redundant genes from Saccharomyces cerevisiae, HAL4/SAT4 and HAL5, that
      encode homologous protein kinases implicated in the regulation of cation uptake.
      Overexpression of these genes increases the tolerance of yeast cells to sodium
      and lithium, whereas gene disruptions result in greater cation sensitivity. These
      phenotypic effects of the mutations correlate with changes in cation uptake and
      are dependent on a functional Trk1-Trk2 potassium transport system. In addition,
      hal4 hal5 and trk1 trk2 mutants exhibit similar phenotypes: (i) they are
      deficient in potassium uptake; (ii) their growth is sensitive to a variety of
      toxic cations, including lithium, sodium, calcium, tetramethylammonium,
      hygromycin B, and low pH; and (iii) they exhibit increased uptake of
      methylammonium, an indicator of membrane potential. These results suggest that
      the Hal4 and Hal5 protein kinases activate the Trk1-Trk2 potassium transporter,
      increasing the influx of potassium and decreasing the membrane potential. The
      resulting loss in electrical driving force reduces the uptake of toxic cations
      and improves salt tolerance. Our data support a role for regulation of membrane
      potential in adaptation to salt stress that is mediated by the Hal4 and Hal5
      kinases.

PMID- 10207058
TI  - Oxidative stress-induced destruction of the yeast C-type cyclin Ume3p requires
      phosphatidylinositol-specific phospholipase C and the 26S proteasome.
AB  - The yeast UME3 (SRB11/SSN3) gene encodes a C-type cyclin that represses the
      transcription of the HSP70 family member SSA1. To relieve this repression, Ume3p
      is rapidly destroyed in cells exposed to elevated temperatures. This report
      demonstrates that Ume3p levels are also reduced in cultures subjected to ethanol
      shock, oxidative stress, or carbon starvation or during growth on nonfermentable
      carbons. Of the three elements (RXXL, PEST, and cyclin box) previously shown to
      be required for heat-induced Ume3p destruction, only the cyclin box regulates
      Ume3p degradation in response to these stressors. The one exception observed was
      growth on nonfermentable carbons, which requires the PEST region. These findings
      indicate that yeast cells contain multiple, independent pathways that mediate
      stress-induced Ume3p degradation. Ume3p destruction in response to oxidative
      stress, but not to ethanol treatment, requires DOA4 and UMP1, two factors
      required for 26S proteasome activity. This result for the first time implicates
      ubiquitin-mediated proteolysis in C-type cyclin regulation. Similarly, the
      presence of a membrane stabilizer (sorbitol) or the loss of phosphatidylinositol
      specific phospholipase C (PLC1) protects Ume3p from oxidative-stress-induced
      degradation. Finally, a ume3 null allele suppresses the growth defect of plc1
      mutants in response to either elevated temperature or the presence of hydrogen
      peroxide. These results indicate that the growth defects observed in plc1 mutants
      are due to the failure to downregulate Ume3p. Taken together, these findings
      support a model in which Plc1p mediates an oxidative-stress signal from the
      plasma membrane that triggers Ume3p destruction through a Doa4p-dependent
      mechanism.

PMID- 10207059
TI  - The linking regions of EBNA1 are essential for its support of replication and
      transcription.
AB  - The ability of distant cis-acting DNA elements to interact functionally has been
      proposed to be mediated by the interaction of proteins associated site
      specifically with those cis-acting elements. We have found that the DNA-linking
      regions of EBNA1 are essential for its contribution to both replication and
      transcription. The synthesis of plasmids containing the Epstein-Barr virus (EBV)
      origin of plasmid replication (oriP) can be mediated entirely by the cellular
      machinery; however, the replicated molecules are lost rapidly from proliferating
      cells. When EBNA1 is provided in trans, plasmids containing oriP (oriP plasmids)
      are synthesized during repeated S phases, and the newly formed daughter molecules
      are precisely segregated to the daughter cells. The contribution(s) of EBNA1 to
      the stable replication of oriP plasmids is therefore likely to be postsynthetic.
      In latently infected cells, EBNA1 also regulates the expression of multiple EBV
      promoters located as many as 10 kbp away. EBNA1 supports replication and
      transcription through binding to oriP; both the ability of EBNA1 to bind to DNA
      and the integrity of its binding sites in oriP are required. However, DNA binding
      by EBNA1 is not sufficient to support replication or transcription, indicating
      that an additional activity (or activities) is required. EBNA1 links DNAs to
      which it binds and can form a loop between the two subelements of oriP, the
      family of repeats and the region of dyad symmetry, each of which contains
      multiple binding sites for EBNA1. We have constructed a set of derivatives of
      EBNA1 which contain both, one, or neither of its linking regions in various
      contexts. Analyses of these derivatives demonstrate that the linking regions of
      EBNA1 are essential for its support of replication and transcription and that the
      ability of derivatives of EBNA1 to link DNAs correlates strongly with their
      support of these activities in cells. These findings indicate that protein
      protein associations of the linking regions of EBNA1 underlie its long-range
      contributions to replication and transcription.

PMID- 10207060
TI  - Transcriptional induction by aromatic amino acids in Saccharomyces cerevisiae.
AB  - Aromatic aminotransferase II, product of the ARO9 gene, catalyzes the first step
      of tryptophan, phenylalanine, and tyrosine catabolism in Saccharomyces
      cerevisiae. ARO9 expression is under the dual control of specific induction and
      nitrogen source regulation. We have here identified UASaro, a 36-bp upstream
      element necessary and sufficient to promote transcriptional induction of reporter
      gene expression in response to tryptophan, phenylalanine, or tyrosine. We then
      isolated mutants in which UASaro-mediated ARO9 transcription is partially or
      totally impaired. Mutations abolishing ARO9 induction affect a gene called ARO80
      (YDR421w), coding for a Zn2Cys6 family transcription factor. A sequence highly
      similar to UASaro was found upstream from the YDR380w gene encoding a homolog of
      bacterial indolepyruvate decarboxylase. In yeast, this enzyme is postulated to
      catalyze the second step of tryptophan catabolism to tryptophol. We show that
      ARO9 and YDR380w (named ARO10) have similar patterns of transcriptional
      regulation and are both under the positive control of Aro80p. Nitrogen regulation
      of ARO9 expression seems not directly to involve the general factor Ure2p, Gln3p,
      Nil1p, Uga43p, or Gzf3p. ARO9 expression appears, rather, to be mainly regulated
      by inducer exclusion. Finally, we show that Gap1p, the general amino acid
      permease, and Wap1p (Ycl025p), a newly discovered inducible amino acid permease
      with broad specificity, are the main aromatic amino acid transporters for
      catabolic purposes.

PMID- 10207061
TI  - Retinoid X receptor (RXR) agonist-induced activation of dominant-negative RXR
      retinoic acid receptor alpha403 heterodimers is developmentally regulated during
      myeloid differentiation.
AB  - The multiple biologic activities of retinoic acid (RA) are mediated through RAR
      and retinoid X receptor (RXR) nuclear receptors that interact with specific DNA
      target sequences as heterodimers (RXR-RAR) or homodimers (RXR-RXR). RA receptor
      activation appears critical to regulating important aspects of hematopoiesis,
      since transducing a COOH-terminally truncated RARalpha exhibiting dominant
      negative activity (RARalpha403) into normal mouse bone marrow generates
      hematopoietic growth factor-dependent cell lines frozen at the multipotent
      progenitor (EML) or committed promyelocyte (MPRO) stages. Nevertheless,
      relatively high, pharmacological concentrations of RA (1 to 10 microM) overcome
      these differentiation blocks and induce terminal granulocytic differentiation of
      the MPRO promyelocytes while potentiating interleukin-3 (IL-3)-induced commitment
      of EML cells to the granulocyte/monocyte lineage. In the present study, we
      utilized RXR- and RAR-specific agonists and antagonists to determine how RA
      overcomes the dominant-negative activity of the truncated RARalpha in these
      different myeloid developmental stages. Unexpectedly, we observed that an RXR
      specific, rather than an RAR-specific, agonist induces terminal granulocytic
      differentiation of MPRO promyelocytes, and this differentiation is associated
      with activation of DNA response elements corresponding to RAR-RXR heterodimers
      rather than RXR-RXR homodimers. This RXR agonist activity is blocked by RAR
      specific antagonists, suggesting extensive cross-talk between the partners of the
      RXR-RARalpha403 heterodimer. In contrast, in the more immature, multipotent EML
      cells we observed that this RXR-specific agonist is inactive either in
      potentiating IL-3-mediated commitment of EML cells to the granulocyte lineage or
      in transactivating RAR-RXR response elements. RA-triggered GALdbd-RARalpha hybrid
      activity in these cells indicates that the multipotent EML cells harbor
      substantial nuclear hormone receptor coactivator activity. However, the histone
      deacetylase (HDAC) inhibitor trichostatin A readily activates an RXR-RAR reporter
      construct in the multipotent EML cells but not in the committed MPRO
      promyelocytes, indicating that differences in HDAC-containing repressor complexes
      in these two closely related but distinct hematopoietic lineages might account
      for the differential activation of the RXR-RARalpha403 heterodimers that we
      observed at these different stages of myeloid development.

PMID- 10207063
TI  - Reactivation of mutant p53 through interaction of a C-terminal peptide with the
      core domain.
AB  - A synthetic 22-mer peptide (peptide 46) derived from the p53 C-terminal domain
      can restore the growth suppressor function of mutant p53 proteins in human tumor
      cells (G. Selivanova et al., Nat. Med. 3:632-638, 1997). Here we demonstrate that
      peptide 46 binds mutant p53. Peptide 46 binding sites were found within both the
      core and C-terminal domains of p53. Lys residues within the peptide were critical
      for both p53 activation and core domain binding. The sequence-specific DNA
      binding of isolated tumor-derived mutant p53 core domains was restored by a C
      terminal polypeptide. Our results indicate that C-terminal peptide binding to the
      core domain activates p53 through displacement of the negative regulatory C
      terminal domain. Furthermore, stabilization of the core domain structure and/or
      establishment of novel DNA contacts may contribute to the reactivation of mutant
      p53. These findings should facilitate the design of p53-reactivating drugs for
      cancer therapy.

PMID- 10207062
TI  - Alien, a highly conserved protein with characteristics of a corepressor for
      members of the nuclear hormone receptor superfamily.
AB  - Some members of nuclear hormone receptors, such as the thyroid hormone receptor
      (TR), silence gene expression in the absence of the hormone. Corepressors, which
      bind to the receptor's silencing domain, are involved in this repression. Hormone
      binding leads to dissociation of corepressors and binding of coactivators, which
      in turn mediate gene activation. Here, we describe the characteristics of Alien,
      a novel corepressor. Alien interacts with TR only in the absence of hormone.
      Addition of thyroid hormone leads to dissociation of Alien from the receptor, as
      shown by the yeast two-hybrid system, glutathione S-transferase pull-down, and
      coimmunoprecipitation experiments. Reporter assays indicate that Alien increases
      receptor-mediated silencing and that it harbors an autonomous silencing function.
      Immune staining shows that Alien is localized in the cell nucleus. Alien is a
      highly conserved protein showing 90% identity between human and Drosophila.
      Drosophila Alien shows similar activities in that it interacts in a hormone
      sensitive manner with TR and harbors an autonomous silencing function. Specific
      interaction of Alien is seen with Drosophila nuclear hormone receptors, such as
      the ecdysone receptor and Seven-up, the Drosophila homologue of COUP-TF1, but not
      with retinoic acid receptor, RXR/USP, DHR 3, DHR 38, DHR 78, or DHR 96. These
      properties, taken together, show that Alien has the characteristics of a
      corepressor. Thus, Alien represents a member of a novel class of corepressors
      specific for selected members of the nuclear hormone receptor superfamily.

PMID- 10207065
TI  - The Saccharomyces cerevisiae hyperrecombination mutant hpr1Delta is synthetically
      lethal with two conditional alleles of the acetyl coenzyme A carboxylase gene and
      causes a defect in nuclear export of polyadenylated RNA.
AB  - In a screen for mutants that display synthetic lethal interaction with hpr1Delta,
      a hyperrecombination mutant of Saccharomyces cerevisiae, we have isolated a novel
      cold-sensitive allele of the acetyl coenzyme A (CoA) carboxylase gene, acc1(cs),
      encoding the rate-limiting enzyme of fatty acid synthesis. The synthetic lethal
      phenotype of the acc1(cs) hpr1Delta double mutant was only partially complemented
      by exogenous fatty acids. hpr1Delta was also synthetically lethal with a
      previously isolated, temperature-sensitive allele of ACC1, mtr7 (mRNA transport),
      indicating that the lethality of the acc1(cs) hpr1Delta double mutant was not
      allele specific. The basis for the interaction between conditional acc1 alleles
      and hpr1Delta was investigated in more detail. In the hpr1Delta mutant
      background, acetyl-CoA carboxylase enzyme activity was reduced about 15-fold and
      steady-state levels of biotinylated Acc1p and ACC1 mRNA were reduced 2-fold. The
      reduced Acc1p activity in hpr1Delta cells, however, did not result in an altered
      lipid or fatty acid composition of the mutant membranes but rendered cells
      hypersensitive to soraphen A, an inhibitor of Acc1p. Similar to mtr7, hpr1Delta
      and acc1(cs) mutant cells displayed a defect in nuclear export of polyadenylated
      RNA. Oversized transcripts were detected in hpr1Delta, and rRNA processing was
      disturbed, but pre-mRNA splicing appeared wild type. Surprisingly, the transport
      defect of hpr1Delta and acc1(cs) mutant cells was accompanied by an altered ring
      shaped structure of the nucleolus. These observations suggest that the basis for
      the synthetic lethal interaction between hpr1Delta and acc1 may lie in a
      functional overlap of the two mutations in nuclear poly(A)+ RNA production and
      export that results in an altered structure of the nucleolus.

PMID- 10207064
TI  - Corepressor required for adenovirus E1B 55,000-molecular-weight protein
      repression of basal transcription.
AB  - Adenovirus E1B 55,000-molecular-weight protein (55K) binds to host cell p53,
      stabilizing it, greatly increasing its affinity for its cognate DNA-binding site,
      and converting it from a regulated activator to a constitutive repressor. Here we
      analyzed the mechanism of repression by the p53-E1B 55K complex. E1B 55K
      repression requires that 55K be tethered to the promoter by binding directly to
      DNA-bound p53. Transcription from an assembled, p53-activated preinitiation
      complex was not repressed by the subsequent addition of E1B 55K, suggesting that
      either sites of 55K interaction with p53 or targets of 55K in the preinitiation
      complex are blocked. Specific E1B 55K repression was observed in reactions
      lacking TFIIA and with recombinant TATA-binding protein in place of TFIID,
      conditions under which p53 does not activate transcription. Thus, E1B 55K does
      not simply inhibit a p53-specific activation mechanism but rather blocks basal
      transcription. As a consequence, E1B 55K may repress transcription from any
      promoter with an associated p53-binding site, no matter what other activators
      associate with the promoter. E1B 55K did not repress basal transcription in
      reactions with recombinant and highly purified general transcription factors and
      RNA polymerase II but rather required a corepressor that copurifies with the
      polymerase.

PMID- 10207067
TI  - Prohibitins regulate membrane protein degradation by the m-AAA protease in
      mitochondria.
AB  - Prohibitins comprise a protein family in eukaryotic cells with potential roles in
      senescence and tumor suppression. Phb1p and Phb2p, members of the prohibitin
      family in Saccharomyces cerevisiae, have been implicated in the regulation of the
      replicative life span of the cells and in the maintenance of mitochondrial
      morphology. The functional activities of these proteins, however, have not been
      elucidated. We demonstrate here that prohibitins regulate the turnover of
      membrane proteins by the m-AAA protease, a conserved ATP-dependent protease in
      the inner membrane of mitochondria. The m-AAA protease is composed of the
      homologous subunits Yta10p (Afg3p) and Yta12p (Rca1p). Deletion of PHB1 or PHB2
      impairs growth of Deltayta10 or Deltayta12 cells but does not affect cell growth
      in the presence of the m-AAA protease. A prohibitin complex with a native
      molecular mass of approximately 2 MDa containing Phb1p and Phb2p forms a
      supercomplex with the m-AAA protease. Proteolysis of nonassembled inner membrane
      proteins by the m-AAA protease is accelerated in mitochondria lacking Phb1p or
      Phb2p, indicating a negative regulatory effect of prohibitins on m-AAA protease
      activity. These results functionally link members of two conserved protein
      families in eukaryotes to the degradation of membrane proteins in mitochondria.

PMID- 10207066
TI  - Cellular activation triggered by the autosomal dominant polycystic kidney disease
      gene product PKD2.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is caused by germ line
      mutations in at least three ADPKD genes. Two recently isolated ADPKD genes, PKD1
      and PKD2, encode integral membrane proteins of unknown function. We found that
      PKD2 upregulated AP-1-dependent transcription in human embryonic kidney 293T
      cells. The PKD2-mediated AP-1 activity was dependent upon activation of the
      mitogen-activated protein kinases p38 and JNK1 and protein kinase C (PKC)
      epsilon, a calcium-independent PKC isozyme. Staurosporine, but not the calcium
      chelator BAPTA [1,2-bis(o-aminophenoxy)ethane-N,N,N', N'-tetraacetate], inhibited
      PKD2-mediated signaling, consistent with the involvement of a calcium-independent
      PKC isozyme. Coexpression of PKD2 with the interacting C terminus of PKD1
      dramatically augmented PKD2-mediated AP-1 activation. The synergistic signaling
      between PKD1 and PKD2 involved the activation of two distinct PKC isozymes, PKC
      alpha and PKC epsilon, respectively. Our findings are consistent with others that
      support a functional connection between PKD1 and PKD2 involving multiple
      signaling pathways that converge to induce AP-1 activity, a transcription factor
      that regulates different cellular programs such as proliferation,
      differentiation, and apoptosis. Activation of these signaling cascades may
      promote the full maturation of developing tubular epithelial cells, while
      inactivation of these signaling cascades may impair terminal differentiation and
      facilitate the development of renal tubular cysts.

PMID- 10207068
TI  - The su(Hw) insulator can disrupt enhancer-promoter interactions when located more
      than 20 kilobases away from the Drosophila achaete-scute complex.
AB  - Here we report that the su(Hw) insulator may not necessarily separate promoters
      from enhancers to allow inhibition of transcription by the su(Hw) protein. For
      this purpose we used the strains of Drosophila melanogaster which carry inversion
      of the region containing the yellow gene and the achaete-scute complex (AS-C).
      Despite the reverse orientation of the region, the AS-C enhancers continue to
      activate achaete and scute gene expression. The su(Hw) insulator, located more
      than 20 kb away from the inversion, facilitates strong suppression of achaete and
      scute gene expression, although is does not separate the promoters from the AS-C
      enhancers.

PMID- 10207069
TI  - Developmentally regulated telomerase activity is correlated with chromosomal
      healing during chromatin diminution in Ascaris suum.
AB  - Telomerase is the ribonucleoprotein complex responsible for the maintenance of
      the physical ends, or telomeres, of most eukaryotic chromosomes. In this study,
      telomerase activity has been identified in cell extracts from the nematode
      Ascaris suum. This parasitic nematode is particularly suited as a model system
      for the study of telomerase, because it shows the phenomenon of chromatin
      diminution, consisting of developmentally programmed chromosomal breakage, DNA
      elimination, and new telomere formation. In vitro, the A. suum telomerase is
      capable of efficiently recognizing and elongating nontelomeric primers with
      nematode-specific telomere repeats by using limited homology at the 3' end of the
      DNA to anneal with the putative telomerase RNA template. The activity of this
      enzyme is developmentally regulated, and it correlates temporally with the
      phenomenon of chromatin diminution. It is up-regulated during the first two
      rounds of embryonic cell divisions, to reach a peak in 4-cell-stage embryos, when
      three presomatic blastomeres prepare for chromatin diminution. The activity
      remains high until the beginning of gastrulation, when the last of the presomatic
      cells undergoes chromatin diminution, and then constantly decreases during
      further development. In summary, our data strongly argue for a role of this
      enzyme in chromosome healing during the process of chromatin diminution.

PMID- 10207070
TI  - Specific acetylation of chromosomal protein HMG-17 by PCAF alters its interaction
      with nucleosomes.
AB  - Nonhistone chromosomal proteins HMG-14 and HMG-17 are closely related nucleosomal
      binding proteins that unfold the higher-order chromatin structure, thereby
      enhancing the transcription and replication potential of chromatin. Here we
      report that PCAF, a transcription coactivator with intrinsic histone
      acetyltransferase activity, specifically acetylates HMG-17 but not HMG-14. Using
      mass spectrum sequence analysis, we identified the lysine at position 2 as the
      predominant site acetylated by PCAF. Lysine 2 is a prominent acetylation site in
      vivo, suggesting that this PCAF-mediated acetylation is physiologically relevant.
      Experiments with HMG-17 deletion mutants and competition studies with various
      protein fragments indicate that the specific acetylation of HMG-17 is not
      determined solely by the primary sequence near the acetylation site. By
      equilibrium dialysis we demonstrated that acetylation reduces the affinity of HMG
      17 to nucleosome cores. In addition, we found that the binding of HMG-14 and HMG
      17 to nucleosome cores inhibits the PCAF-mediated acetylation of histone H3.
      Thus, the presence of HMG-14 and HMG-17 affects the ability of PCAF to acetylate
      chromatin, while the acetylation of HMG-17 reduces its binding affinity to
      chromatin. Conceivably, in HMG-17-containing chromatin, acetylation of HMG-17
      precedes the acetylation of histones.

PMID- 10207071
TI  - Cooperation between phosphorylation and acetylation processes in transcriptional
      control.
AB  - We previously reported that the activation of the M promoter of the human choline
      acetyltransferase (ChAT) gene by butyrate and trapoxin in transfected CHP126
      cells is blocked by PD98059, a specific mitogen-activated protein kinase kinase
      (MEK) inhibitor (E. Espinos and M. J. Weber, Mol. Brain Res. 56:118-124, 1998).
      We now report that the transcriptional effects of histone deacetylase inhibitors
      are mediated by an H7-sensitive serine/threonine protein kinase. Activation of
      the ChAT promoter by butyrate and trapoxin was blocked by 50 microM H7 in both
      transient- and stable-transfection assays. Overexpression of p300, a coactivator
      protein endowed with histone acetyltransferase activity, stimulated the ChAT
      promoter and had a synergistic effect on butyrate treatment. These effects were
      blocked by H7 and by overexpressed adenovirus E1A 12S protein. Moreover, both H7
      and PD98059 suppressed the activation of the Rous sarcoma virus (RSV) and simian
      virus 40 promoters by butyrate in transfection experiments. Similarly, the
      induction of the cellular histone H1(0) gene by butyrate in CHP126 cells was
      blocked by H7 and by PD98059. Previous data (L. Cuisset, L. Tichonicky, P.
      Jaffray, and M. Delpech, J. Biol. Chem. 272:24148-24153, 1997) showed that the
      induction of the H1(0) gene by butyrate is blocked by okadaic acid, an inhibitor
      of protein phosphatases. We now show that the activation of the ChAT and RSV
      promoters by butyrate in transfected CHP126 cells is also blocked by 200 nM
      okadaic acid. Western blotting and in vivo metabolic labeling experiments showed
      that butyrate has a biphasic effect on histone H3 phosphorylation, i.e.,
      depression for up to 16 h followed by stimulation. The data thus strongly suggest
      that the transcriptional effects of histone deacetylase inhibitors are mediated
      through the activation of MEK1 and of an H7-sensitive protein kinase in addition
      to protein phosphatases.

PMID- 10207072
TI  - Transcriptional cross talk between NF-kappaB and p53.
AB  - Many cellular stimuli result in the induction of both the tumor suppressor p53
      and NF-kappaB. In contrast to activation of p53, which is associated with the
      induction of apoptosis, stimulation of NF-kappaB has been shown to promote
      resistance to programmed cell death. These observations suggest that a regulatory
      mechanism must exist to integrate these opposing outcomes and coordinate this
      critical cellular decision-making event. Here we show that both p53 and NF-kappaB
      inhibit each other's ability to stimulate gene expression and that this process
      is controlled by the relative levels of each transcription factor. Expression of
      either wild-type p53 or the RelA(p65) NF-kappaB subunit suppresses stimulation of
      transcription by the other factor from a reporter plasmid in vivo. Moreover,
      endogenous, tumor necrosis factor alpha-activated NF-kappaB will inhibit
      endogenous wild-type p53 transactivation. Following exposure to UV light,
      however, the converse is observed, with p53 downregulating NF-kappaB-mediated
      transcriptional activation. Both p53 and RelA(p65) interact with the
      transcriptional coactivator proteins p300 and CREB-binding protein (CBP), and we
      demonstrate that these results are consistent with competition for a limiting
      pool of p300/CBP complexes in vivo. These observations have many implications for
      regulation of the transcriptional decision-making mechanisms that govern cellular
      processes such as apoptosis. Furthermore, they suggest a previously unrealized
      mechanism through which dysregulated NF-kappaB can contribute to tumorigenesis
      and disease.

PMID- 10207073
TI  - CREB-Binding protein acetylates hematopoietic transcription factor GATA-1 at
      functionally important sites.
AB  - The transcription factor GATA-1 is a key regulator of erythroid-cell
      differentiation and survival. We have previously shown that the transcriptional
      cofactor CREB-binding protein (CBP) binds to the zinc finger domain of GATA-1,
      markedly stimulates the transcriptional activity of GATA-1, and is required for
      erythroid differentiation. Here we report that CBP, but not p/CAF, acetylates
      GATA-1 at two highly conserved lysine-rich motifs present at the C-terminal tails
      of both zinc fingers. Using [3H]acetate labelling experiments and anti-acetyl
      lysine immunoprecipitations, we show that GATA-1 is acetylated in vivo at the
      same sites acetylated by CBP in vitro. In addition, we show that CBP stimulates
      GATA-1 acetylation in vivo in an E1A-sensitive manner, thus establishing a
      correlation between acetylation and transcriptional activity of GATA-1.
      Acetylation in vitro did not alter the ability of GATA-1 to bind DNA, and
      mutations in either motif did not affect DNA binding of GATA-1 expressed in
      mammalian cells. Since certain functions of GATA-1 are revealed only in an
      erythroid environment, GATA-1 constructs were examined for their ability to
      trigger terminal differentiation when introduced into a GATA-1-deficient
      erythroid cell line. We found that mutations in either acetylation motif
      partially impaired the ability of GATA-1 to induce differentiation while
      mutations in both motifs abrogated it completely. Taken together, these data
      indicate that CBP is an important cofactor for GATA-1 and suggest a novel
      mechanism in which acetylation by CBP regulates GATA-1 activity in erythroid
      cells.

PMID- 10207074
TI  - The one-kilobase DNA fragment upstream of the ardC actin gene of Physarum
      polycephalum is both a replicator and a promoter.
AB  - The 1-kb DNA fragment upstream of the ardC actin gene of Physarum polycephalum
      promotes the transcription of a reporter gene either in a transient-plasmid assay
      or as an integrated copy in an ectopic position, defining this region as the
      transcriptional promoter of the ardC gene (PardC). Since we mapped an origin of
      replication activated at the onset of S phase within this same fragment, we
      examined the pattern of replication of a cassette containing the PardC promoter
      and the hygromycin phosphotransferase gene, hph, integrated into two different
      chromosomal sites. In both cases, we show by two-dimensional agarose gel
      electrophoresis that an efficient, early activated origin coincides with the
      ectopic PardC fragment. One of the integration sites was a normally late
      replicating region. The presence of the ectopic origin converted this late
      replicating domain into an early-replicating domain in which replication forks
      propagate with kinetics indistinguishable from those of the native PardC
      replicon. This is the first demonstration that initiation sites for DNA
      replication in Physarum correspond to cis-acting replicator sequences. This work
      also confirms the close proximity of a replication origin and a promoter, with
      both functions being located within the 1-kb proximal region of the ardC actin
      gene. A more precise location of the replication origin with respect to the
      transcriptional promoter must await the development of a functional autonomously
      replicating sequence assay in Physarum.

PMID- 10207075
TI  - Rec8p, a meiotic recombination and sister chromatid cohesion phosphoprotein of
      the Rad21p family conserved from fission yeast to humans.
AB  - Our work and that of others defined mitosis-specific (Rad21 subfamily) and
      meiosis-specific (Rec8 subfamily) proteins involved in sister chromatid cohesion
      in several eukaryotes, including humans. Mutation of the fission yeast
      Schizosaccharomyces pombe rec8 gene was previously shown to confer a number of
      meiotic phenotypes, including strong reduction of recombination frequencies in
      the central region of chromosome III, absence of linear element polymerization,
      reduced pairing of homologous chromosomes, reduced sister chromatid cohesion,
      aberrant chromosome segregation, defects in spore formation, and reduced spore
      viability. Here we extend the description of recombination reduction to the
      central regions of chromosomes I and II. We show at the protein level that
      expression of rec8 is meiosis specific and that Rec8p localizes to approximately
      100 foci per prophase nucleus. Rec8p was present in an unphosphorylated form
      early in meiotic prophase but was phosphorylated prior to meiosis I, as
      demonstrated by analysis of the mei4 mutant blocked before meiosis I. Evidence
      for the persistence of Rec8p beyond meiosis I was obtained by analysis of the
      mutant mes1 blocked before meiosis II. A human gene, which we designate hrec8,
      showed significant primary sequence similarity to rec8 and was mapped to
      chromosome 14. High mRNA expression of mouse and human rec8 genes was found only
      in germ line cells, specifically in testes and, interestingly, in spermatids.
      hrec8 was also expressed at a low level in the thymus. Sequence similarity and
      testis-specific expression indicate evolutionarily conserved functions of Rec8p
      in meiosis. Possible roles of Rec8p in the integration of different meiotic
      events are discussed.

PMID- 10207077
TI  - The carboxyl terminus of RNA helicase A contains a bidirectional nuclear
      transport domain.
AB  - Human RNA helicase A was recently identified to be a shuttle protein which
      interacts with the constitutive transport element (CTE) of type D retroviruses.
      Here we show that a domain of 110 amino acids at the carboxyl terminus of
      helicase A is both necessary and sufficient for nuclear localization as well as
      rapid nuclear export of glutathione S-transferase fusion proteins. The import and
      export activities of this domain overlap but are separable by point mutations.
      This bidirectional nuclear transport domain (NTD) has no obvious sequence
      homology to previously identified nuclear import or export signals. However, the
      Ran-dependent nuclear import of NTD was efficiently competed by excess amounts of
      the nuclear localization signal (NLS) peptide from simian virus 40 large T
      antigen, suggesting that import is mediated by the classical NLS pathway. The
      nuclear export pathway accessed by NTD is insensitive to leptomycin B and thus is
      distinct from the leucine-rich nuclear export signal pathway mediated by CRM1.

PMID- 10207076
TI  - The tmp gene, encoding a membrane protein, is a c-Myc target with a tumorigenic
      activity.
AB  - The c-Myc oncoprotein induces cell proliferation and transformation through its
      activity as a transcription factor. Uncovering the genes regulated by c-Myc is an
      essential step for understanding these processes. We recently isolated the tumor
      associated membrane protein gene, Tmp, from a c-myc-induced mouse brain tumor.
      Here we show that Tmp is specifically highly expressed in mammary tumors and T
      cell lymphomas which develop in c-myc transgenic mice, suggesting that Tmp
      expression is a general characteristic of c-Myc-induced tumors. In addition, Tmp
      expression is induced upon serum stimulation of fibroblasts as shown in a time
      course closely correlated with c-myc expression. We have isolated the Tmp
      promoter region and identified a putative c-Myc binding element, CACGTG, located
      in the first intron of the gene. We show here that constructs containing the Tmp
      regulatory region fused to a reporter gene are activated by c-Myc through this
      CACGTG element and that the c-Myc-Max protein complex can bind to this element.
      Moreover, an inducible form of c-Myc, the MycER fusion protein, can activate the
      endogenous Tmp gene. We also show that Tmp-overexpressing fibroblasts induce
      rapidly growing tumors when injected into nude mice, suggesting that Tmp may
      possess a tumorigenic activity. Thus, TMP, a member of a novel family of membrane
      glycoproteins with a suggested role in cellular contact, is a c-Myc target and is
      possibly involved in c-Myc-induced transformation.

PMID- 10207079
TI  - Stem-loop binding protein facilitates 3'-end formation by stabilizing U7 snRNP
      binding to histone pre-mRNA.
AB  - The 3' end of histone mRNA is formed by an endonucleolytic cleavage of the
      primary transcript after a conserved stem-loop sequence. The cleavage reaction
      requires at least two trans-acting factors: the stem-loop binding protein (SLBP),
      which binds the stem-loop sequence, and the U7 snRNP that interacts with a
      sequence downstream from the cleavage site. Removal of SLBP from a nuclear
      extract abolishes 3'-end processing, and the addition of recombinant SLBP
      restores processing activity of the depleted extract. To determine the regions of
      human SLBP necessary for 3' processing, various deletion mutants of the protein
      were tested for their ability to complement the SLBP-depleted extract. The entire
      N-terminal domain and the majority of the C-terminal domain of human SLBP are
      dispensable for processing. The minimal protein that efficiently supports
      cleavage of histone pre-mRNA consists of 93 amino acids containing the 73-amino
      acid RNA-binding domain and 20 amino acids located immediately next to its C
      terminus. Replacement of these 20 residues with an unrelated sequence in the
      context of the full-length SLBP reduces processing >90%. Coimmunoprecipitation
      experiments with the anti-SLBP antibody demonstrated that SLBP and U7 snRNP form
      a stable complex only in the presence of pre-mRNA substrates containing a
      properly positioned U7 snRNP binding site. One role of SLBP is to stabilize the
      interaction of the histone pre-mRNA with U7 snRNP.

PMID- 10207078
TI  - Extracellular signal-regulated kinase activates topoisomerase IIalpha through a
      mechanism independent of phosphorylation.
AB  - The mitogen-activated protein (MAP) kinases, extracellular signal-related kinase
      1 (ERK1) and ERK2, regulate cellular responses by mediating extracellular growth
      signals toward cytoplasmic and nuclear targets. A potential target for ERK is
      topoisomerase IIalpha, which becomes highly phosphorylated during mitosis and is
      required for several aspects of nucleic acid metabolism, including chromosome
      condensation and daughter chromosome separation. In this study, we demonstrated
      interactions between ERK2 and topoisomerase IIalpha proteins by
      coimmunoprecipitation from mixtures of purified enzymes and from nuclear
      extracts. In vitro, diphosphorylated active ERK2 phosphorylated topoisomerase
      IIalpha and enhanced its specific activity by sevenfold, as measured by DNA
      relaxation assays, whereas unphosphorylated ERK2 had no effect. However,
      activation of topoisomerase II was also observed with diphosphorylated inactive
      mutant ERK2, suggesting a mechanism of activation that depends on the
      phosphorylation state of ERK2 but not on its kinase activity. Nevertheless,
      activation of ERK by transient transfection of constitutively active mutant MAP
      kinase kinase 1 (MKK1) enhanced endogenous topoisomerase II activity by fourfold.
      Our findings indicate that ERK regulates topoisomerase IIalpha in vitro and in
      vivo, suggesting a potential target for the MKK/ERK pathway in the modulation of
      chromatin reorganization events during mitosis and in other phases of the cell
      cycle.

PMID- 10207080
TI  - FKLF, a novel Kruppel-like factor that activates human embryonic and fetal beta
      like globin genes.
AB  - A cDNA encoding a novel Kruppel-type zinc finger protein, FKLF, was cloned from
      fetal globin-expressing human fetal erythroid cells. The deduced polypeptide
      sequence composed of 512 amino acids revealed that, like Sp1 and EKLF, FKLF has
      three contiguous zinc fingers at the near carboxyl-terminal end. A long amino
      terminal domain is characterized by the presence of two acidic and two proline
      rich regions. Reverse transcription (RT)-PCR assays using various cell lines
      demonstrated that the FKLF mRNA is expressed predominantly in erythroid cells.
      FKLF message is detectable by RT-PCR in fetal liver but not in adult bone marrow
      cells. As predicted from its structural features, FKLF is a transcriptional
      activator. In luciferase assays FKLF activated the gamma- and epsilon-globin gene
      promoters, and, to a much lower degree, the beta-globin promoter. Studies of HS2
      gamma gene reporter constructs carrying CACCC box deletions revealed that the
      CACCC box sequence of the gamma gene promoter mediates the activation of the
      gamma gene by FKLF. Other erythroid promoters (GATA-1, glycophorin B,
      ferrochelatase, porphobilinogen deaminase, and 5-aminolevulinate synthase)
      containing CACCC elements or GC-rich potential Sp1-binding sites were activated
      minimally, if at all, by FKLF, indicating that FKLF is not a general activator of
      genes carrying the CACCC motifs. Transfection of K562 cells with FKLF cDNA
      enhanced the expression of the endogenous epsilon- and gamma-globin genes,
      suggesting an in vivo role of FKLF in fetal and embryonic globin gene expression.
      Our results indicate that the protein potentially encoded by the FKLF cDNA acts
      as a transcriptional activator of embryonic and fetal beta-like globin genes.

PMID- 10207081
TI  - Rho3 of Saccharomyces cerevisiae, which regulates the actin cytoskeleton and
      exocytosis, is a GTPase which interacts with Myo2 and Exo70.
AB  - The Rho3 protein plays a critical role in the budding yeast Saccharomyces
      cerevisiae by directing proper cell growth. Rho3 appears to influence cell growth
      by regulating polarized secretion and the actin cytoskeleton, since rho3 mutants
      exhibit large rounded cells with an aberrant actin cytoskeleton. To gain insights
      into how Rho3 influences these events, we have carried out a yeast two-hybrid
      screen using an S. cerevisiae cDNA library to identify proteins interacting with
      Rho3. Two proteins, Exo70 and Myo2, were identified in this screen. Interactions
      with these two proteins are greatly reduced or abolished when mutations are
      introduced into the Rho3 effector domain. In addition, a type of mutation known
      to produce dominant negative mutants of Rho proteins abolished the interaction
      with both of these proteins. In contrast, Rho3 did not interact with protein
      kinase C (Pkc1), an effector of another Rho family protein, Rho1, nor did Rho1
      interact with Exo70 or Myo2. Rho3 did interact with Bni1, another effector of
      Rho1, but less efficiently than with Rho1. The interaction between Rho3 and Exo70
      and between Rho3 and Myo2 was also demonstrated with purified proteins. The
      interaction between Exo70 and Rho3 in vitro was dependent on the presence of GTP,
      since Rho3 complexed with guanosine 5'-O-(3-thiotriphosphate) interacted more
      efficiently with Exo70 than Rho3 complexed with guanosine 5'-O-(3
      thiodiphosphate). Overlapping subcellular localization of the Rho3 and Exo70
      proteins was demonstrated by indirect immunofluorescence. In addition, patterns
      of localization of both Exo70 and Rho3 were altered when a dominant active allele
      of RHO3, RHO3(E129,A131), which causes a morphological abnormality, was
      expressed. These results provide a direct molecular basis for the action of Rho3
      on exocytosis and the actin cytoskeleton.

PMID- 10207083
TI  - Identification of the novel player deltaEF1 in estrogen transcriptional cascades.
AB  - Although many genes are regulated by estrogen, very few have been shown to
      directly bind the estrogen receptor complex. Therefore, transcriptional cascades
      probably occur in which the estrogen receptor directly binds to a target gene
      that encodes another transcription factor that subsequently regulates additional
      genes. Through the use of a differential display assay, a transcription factor
      has been identified that may be involved in estrogen transcriptional cascades.
      This report demonstrates that transcription factor deltaEF1 is induced eightfold
      by estrogen in the chick oviduct. Furthermore, the regulation by estrogen occurs
      at the transcriptional level and is likely to be a direct effect of the estrogen
      receptor complex, as it does not require concomitant protein synthesis. A
      putative binding site was identified in the 5'-flanking region of the chick
      ovalbumin gene identifying it as a possible target gene for regulation by
      deltaEF1. Characterization of this binding site revealed that deltaEF1 binds to
      and regulates the chick ovalbumin gene. Thus, a novel regulatory cascade that is
      triggered by estrogen has been defined.

PMID- 10207082
TI  - Yeast mutants affecting possible quality control of plasma membrane proteins.
AB  - Mutations gef1, stp22, STP26, and STP27 in Saccharomyces cerevisiae were
      identified as suppressors of the temperature-sensitive alpha-factor receptor
      (mutation ste2-3) and arginine permease (mutation can1(ts)). These suppressors
      inhibited the elimination of misfolded receptors (synthesized at 34 degrees C) as
      well as damaged surface receptors (shifted from 22 to 34 degrees C). The stp22
      mutation (allelic to vps23 [M. Babst and S. Emr, personal communication] and the
      STP26 mutation also caused missorting of carboxypeptidase Y, and ste2-3 was
      suppressed by mutations vps1, vps8, vps10, and vps28 but not by mutation vps3. In
      the stp22 mutant, both the mutant and the wild-type receptors (tagged with green
      fluorescent protein [GFP]) accumulated within an endosome-like compartment and
      were excluded from the vacuole. GFP-tagged Stp22p also accumulated in this
      compartment. Upon reaching the vacuole, cytoplasmic domains of both mutant and
      wild-type receptors appeared within the vacuolar lumen. Stp22p and Gef1p are
      similar to tumor susceptibility protein TSG101 and voltage-gated chloride
      channel, respectively. These results identify potential elements of plasma
      membrane quality control and indicate that cytoplasmic domains of membrane
      proteins are translocated into the vacuolar lumen.

PMID- 10207084
TI  - Engagement of the cellular receptor for glycoprotein B of human cytomegalovirus
      activates the interferon-responsive pathway.
AB  - Cells respond to contact with human cytomegalovirus (HCMV) virions by initiating
      intracellular signaling and gene expression characteristic of the interferon
      (IFN)-responsive pathway. Herein, we demonstrate that a principal mechanism of
      HCMV-induced signal transduction is via an interaction of the primary viral
      ligand, glycoprotein B (gB), with its cellular receptor. Cells incubated with a
      purified, soluble form of gB resulted in the transcriptional upregulation of IFN
      responsive genes OAS and ISG54 (encoding 2'-5' oligoadenylate synthetase and an
      IFN-stimulated gene product of 54 kDa) to a comparable level as virions or IFN.
      Gene induction was an immediate and direct response to gB which did not require
      de novo protein synthesis. Neither the initial virus attachment site, heparan
      sulfate proteoglycans, nor the IFN-alpha/beta or IFN-gamma receptors are involved
      in the response. Pleotropic protein phosphorylation was required for cellular
      gene induction, and the mitogen-activated protein kinases ERK1 and ERK2 were
      activated in response to the ligand. Together these data indicate that a
      principal means by which cytomegalovirus induces intracellular signaling and
      activation of the interferon-responsive pathway is via an interaction of gB with
      an as yet unidentified, likely novel cellular receptor that interfaces with the
      IFN signaling pathway.

PMID- 10207085
TI  - The catenin p120(ctn) interacts with Kaiso, a novel BTB/POZ domain zinc finger
      transcription factor.
AB  - p120(ctn) is an Armadillo repeat domain protein with structural similarity to the
      cell adhesion cofactors beta-catenin and plakoglobin. All three proteins interact
      directly with the cytoplasmic domain of the transmembrane cell adhesion molecule
      E-cadherin; beta-catenin and plakoglobin bind a carboxy-terminal region in a
      mutually exclusive manner, while p120 binds the juxtamembrane region. Unlike beta
      catenin and plakoglobin, p120 does not interact with alpha-catenin, the tumor
      suppressor adenomatous polyposis coli (APC), or the transcription factor Lef-1,
      suggesting that it has unique binding partners and plays a distinct role in the
      cadherin-catenin complex. Using p120 as bait, we conducted a yeast two-hybrid
      screen and identified a novel transcription factor which we named Kaiso. Kaiso's
      deduced amino acid sequence revealed an amino-terminal BTB/POZ protein-protein
      interaction domain and three carboxy-terminal zinc fingers of the C2H2 DNA
      binding type. Kaiso thus belongs to a rapidly growing family of POZ-ZF
      transcription factors that include the Drosophila developmental regulators
      Tramtrak and Bric a brac, and the human oncoproteins BCL-6 and PLZF, which are
      causally linked to non-Hodgkins' lymphoma and acute promyelocytic leukemia,
      respectively. Monoclonal antibodies to Kaiso were generated and used to
      immunolocalize the protein and confirm the specificity of the p120-Kaiso
      interaction in mammalian cells. Kaiso specifically coprecipitated with a variety
      of p120-specific monoclonal antibodies but not with antibodies to alpha- or beta
      catenin, E-cadherin, or APC. Like other POZ-ZF proteins, Kaiso localized to the
      nucleus and was associated with specific nuclear dots. Yeast two-hybrid
      interaction assays mapped the binding domains to Arm repeats 1 to 7 of p120 and
      the carboxy-terminal 200 amino acids of Kaiso. In addition, Kaiso homodimerized
      via its POZ domain but it did not heterodimerize with BCL-6, which
      heterodimerizes with PLZF. The involvement of POZ-ZF proteins in development and
      cancer makes Kaiso an interesting candidate for a downstream effector of cadherin
      and/or p120 signaling.

PMID- 10207086
TI  - A nonessential HP1-like protein affects starvation-induced assembly of condensed
      chromatin and gene expression in macronuclei of Tetrahymena thermophila.
AB  - Heterochromatin represents a specialized chromatin environment vital to both the
      repression and expression of certain eukaryotic genes. One of the best-studied
      heterochromatin-associated proteins is Drosophila HP1. In this report, we have
      disrupted all somatic copies of the Tetrahymena HHP1 gene, which encodes an HP1
      like protein, Hhp1p, in macronuclei (H. Huang, E. A. Wiley, R. C. Lending, and C.
      D. Allis, Proc. Natl. Acad. Sci. USA 95:13624-13629, 1998). Unlike the Drosophila
      HP1 gene, HHP1 is not essential in Tetrahymena spp., and during vegetative growth
      no clear phenotype is observed in cells lacking Hhp1p (DeltaHHP1). However,
      during a shift to nongrowth conditions, the survival rate of DeltaHHP1 cells is
      reduced compared to that of wild-type cells. Upon starvation, Hhp1p becomes
      hyperphosphorylated concomitant with a reduction in macronuclear volume and an
      increase in the size of electron-dense chromatin bodies; neither of these
      morphological changes occurs in the absence of Hhp1p. Activation of two
      starvation-induced genes (ngoA and CyP) is significantly reduced in DeltaHHP1
      cells while, in contrast, the expression of several growth-related or
      constitutively expressed genes is comparable to that in wild-type cells. These
      results suggest that Hhp1p functions in the establishment and/or maintenance of a
      specialized condensed chromatin environment that facilitates the expression of
      certain genes linked to a starvation-induced response.

PMID- 10207087
TI  - Functional and physical interactions between AML1 proteins and an ETS protein,
      MEF: implications for the pathogenesis of t(8;21)-positive leukemias.
AB  - The AML1 and ETS families of transcription factors play critical roles in
      hematopoiesis; AML1, and its non-DNA-binding heterodimer partner CBFbeta, are
      essential for the development of definitive hematopoiesis in mice, whereas the
      absence of certain ETS proteins creates specific defects in lymphopoiesis or
      myelopoiesis. The promoter activities of numerous genes expressed in
      hematopoietic cells are regulated by AML1 proteins or ETS proteins. MEF (for
      myeloid ELF-1-like factor) is a recently cloned ETS family member that, like
      AML1B, can strongly transactivate several of these promoters, which led us to
      examine whether MEF functionally or physically interacts with AML1 proteins. In
      this study, we demonstrate direct interactions between MEF and AML1 proteins,
      including the AML1/ETO fusion protein, in t(8;21)-positive acute myeloid leukemia
      (AML) cells. Using mutational analysis, we identified a novel ETS-interacting
      subdomain (EID) in the C-terminal portion of the Runt homology domain (RHD) in
      AML1 proteins and determined that the N-terminal region of MEF was responsible
      for its interaction with AML1. MEF and AML1B synergistically transactivated an
      interleukin 3 promoter reporter gene construct, yet the activating activity of
      MEF was abolished when MEF was coexpressed with AML1/ETO. The repression by
      AML1/ETO was independent of DNA binding but depended on its ability to interact
      with MEF, suggesting that AML1/ETO can repress genes not normally regulated by
      AML1 via protein-protein interactions. Interference with MEF function by AML1/ETO
      may lead to dysregulation of genes important for myeloid differentiation, thereby
      contributing to the pathogenesis of t(8;21) AML.

PMID- 10207089
TI  - Hepatocyte growth factor releases mink epithelial cells from transforming growth
      factor beta1-induced growth arrest by restoring Cdk6 expression and cyclin E
      associated Cdk2 activity.
AB  - Transforming growth factor beta (TGF-beta) potently suppresses Mv1Lu mink
      epithelial cell growth, whereas hepatocyte growth factor (HGF) counteracts TGF
      beta-mediated growth inhibition and induces Mv1Lu cell proliferation (J. Taipale
      and J. Keski-Oja, J. Biol. Chem. 271:4342-4348, 1996). By addressing the cell
      cycle regulatory mechanisms involved in HGF-mediated release of Mv1Lu cells from
      TGF-beta inhibition, we show that increased DNA replication is accompanied by
      phosphorylation of the retinoblastoma protein and alternative regulation of
      cyclin-Cdk-inhibitor complexes. While TGF-beta treatment decreased the expression
      of Cdk6, this effect was counteracted by HGF, followed by partial restoration of
      cyclin D2-associated kinase activity. Notably, HGF failed to prevent TGF-beta
      induction of p15 and its association with Cdk6. However, HGF reversed the TGF
      beta-mediated decrease in Cdk6-associated p27 and cyclin D2-associated Cdk6,
      suggesting that HGF modifies the TGF-beta response at the level of G1 cyclin
      complex formation. Counteraction of TGF-beta regulation of Cdk6 by HGF may in
      turn affect the association of p27 with Cdk2-cyclin E complexes. Though HGF did
      not differentially regulate the total levels of p27 in TGF-beta-treated cells,
      p27 immunodepletion experiments suggested that upon treatment with both growth
      factors, less p27 is associated with Cdk2-cyclin E complexes, in parallel with
      restoration of the active form of Cdk2 and the associated kinase activity. The
      results demonstrate that HGF intercepts TGF-beta cell cycle regulation at
      multiple points, affecting both G1 and G1-S cyclin kinase activities.

PMID- 10207088
TI  - Reciprocal modulatory interaction between human immunodeficiency virus type 1 Tat
      and transcription factor NFAT1.
AB  - Human immunodeficiency virus type 1 (HIV-1) gene expression is regulated by
      interactions between both viral and host factors. These interactions are also
      responsible for changes in the expression of many host cell genes, including
      cytokines and other immune regulators, which may account for the state of
      immunological dysregulation that characterizes HIV-1 infection. We have
      investigated the role of a host cell protein, the transcription factor NFAT1, in
      HIV-1 pathogenesis. We show that NFAT1 interacts with Tat and that this
      interaction, which involves the major transactivation domain of NFAT1 and the
      amino-terminal region of Tat, results in a reciprocal modulatory interplay
      between the proteins: whereas Tat enhances NFAT1-driven transcription in Jurkat T
      cells, NFAT1 represses Tat-mediated transactivation of the HIV-1 long terminal
      repeat (LTR). Moreover, NFAT1 binds to the kappaB sites on the viral LTR and
      negatively regulates NF-kappaB-mediated activation of HIV-1 transcription, by
      competing with NF-kappaB1 for its binding sites on the HIV-1 LTR. Tat-mediated
      enhancement of NFAT1 transactivation may explain the upregulation of interleukin
      2 and other cytokines that occurs during HIV-1 infection. We discuss the
      potentially opposing roles of NFAT1 and another family member, NFAT2, in
      regulating gene transcription of HIV-1 and endogenous cytokine genes.

PMID- 10207090
TI  - Structural motifs involved in ubiquitin-mediated processing of the NF-kappaB
      precursor p105: roles of the glycine-rich region and a downstream ubiquitination
      domain.
AB  - The ubiquitin proteolytic system plays a major role in a variety of basic
      cellular processes. In the majority of these processes, the target proteins are
      completely degraded. In one exceptional case, generation of the p50 subunit of
      the transcriptional regulator NF-kappaB, the precursor protein p105 is processed
      in a limited manner: the N-terminal domain yields the p50 subunit, whereas the C
      terminal domain is degraded. The identity of the mechanisms involved in this
      unique process have remained elusive. It has been shown that a Gly-rich region
      (GRR) at the C-terminal domain of p50 is an important processing signal. Here we
      show that the GRR does not interfere with conjugation of ubiquitin to p105 but
      probably does interfere with the processing of the ubiquitin-tagged precursor by
      the 26S proteasome. Structural analysis reveals that a short sequence containing
      a few Gly residues and a single essential Ala is sufficient to generate p50.
      Mechanistically, the presence of the GRR appears to stop further degradation of
      p50 and to stabilize the molecule. It appears that the localization of the GRR
      within p105 plays an important role in directing processing: transfer of the GRR
      within p105 or insertion of the GRR into homologous or heterologous proteins is
      not sufficient to promote processing in most cases, which is probably due to the
      requirement for an additional specific ubiquitination and/or recognition
      domain(s). Indeed, we have shown that amino acid residues 441 to 454 are
      important for processing. In particular, both Lys 441 and Lys 442 appear to serve
      as major ubiquitination targets, while residues 446 to 454 are independently
      important for processing and may serve as the ubiquitin ligase recognition motif.

PMID- 10207091
TI  - RAG-2 promotes heptamer occupancy by RAG-1 in the assembly of a V(D)J initiation
      complex.
AB  - V(D)J recombination occurs at recombination signal sequences (RSSs) containing
      conserved heptamer and nonamer elements. RAG-1 and RAG-2 initiate recombination
      by cleaving DNA between heptamers and antigen receptor coding segments. RAG-1
      alone contacts the nonamer but interacts weakly, if at all, with the heptamer.
      RAG-2 by itself has no DNA-binding activity but promotes heptamer occupancy in
      the presence of RAG-1; how RAG-2 collaborates with RAG-1 has been poorly
      understood. Here we examine the composition of RAG-RSS complexes and the relative
      contributions of RAG-1 and RAG-2 to heptamer binding. RAG-1 exists as a dimer in
      complexes with an isolated RSS bearing a 12-bp spacer, regardless of whether RAG
      2 is present; only a single subunit of RAG-1, however, participates in nonamer
      binding. In contrast, multimeric RAG-2 is not detectable by electrophoretic
      mobility shift assays in complexes containing both RAG proteins. DNA-protein
      photo-cross-linking demonstrates that heptamer contacts, while enhanced by RAG-2,
      are mediated primarily by RAG-1. RAG-2 cross-linking, while less efficient than
      that of RAG-1, is detectable near the heptamer-coding junction. These
      observations provide evidence that RAG-2 alters the conformation or orientation
      of RAG-1, thereby stabilizing interactions of RAG-1 with the heptamer, and
      suggest that both proteins interact with the RSS near the site of cleavage.

PMID- 10207092
TI  - Temporal activation of the sea urchin late H1 gene requires stage-specific
      phosphorylation of the embryonic transcription factor SSAP.
AB  - Stage-specific activator protein (SSAP) is a 41-kDa polypeptide that binds to
      embryonic enhancer elements of the sea urchin late H1 gene. These enhancer
      elements mediate the transcriptional activation of the late H1 gene in a
      temporally specific manner at the mid-blastula stage of embryogenesis. Although
      SSAP can transactivate the late H1 gene only at late stages of the development,
      it resides in the sea urchin nucleus and maintains DNA binding activity
      throughout early embryogenesis. In addition, it has been shown that SSAP
      undergoes a conversion from a 41-kDa monomer to a approximately 80- to 100-kDa
      dimer when the late H1 gene is activated. We have demonstrated that SSAP is
      differentially phosphorylated during embryogenesis. Serine 87, a cyclic AMP
      dependent protein kinase consensus site located in the N-terminal DNA binding
      domain, is constitutively phosphorylated. At the mid-blastula stage of
      embryogenesis, temporally correlated with SSAP dimer formation and late H1 gene
      activation, a threonine residue in the C-terminal transactivation domain is
      phosphorylated. This phosphorylation can be catalyzed by a break-ended double
      stranded DNA-activated protein kinase activity from the sea urchin nucleus in
      vitro. Microinjection of synthetic SSAP mRNAs encoding either serine or threonine
      phosphorylation mutants results in the failure to transactivate reporter genes
      that contain the enhancer element, suggesting that both serine and threonine
      phosphorylation of SSAP are required for the activation of the late H1 gene.
      Furthermore, SSAP can undergo blastula-stage-specific homodimerization through
      its GQ-rich transactivation domain. The late-specific threonine phosphorylation
      in this domain is essential for the dimer assembly. These observations indicate
      that temporally regulated SSAP activation is promoted by threonine
      phosphorylation on its transactivation domain, which triggers the formation of a
      transcriptionally active SSAP homodimer.

PMID- 10207093
TI  - Reversible tumorigenesis induced by deficiency of vasodilator-stimulated
      phosphoprotein.
AB  - Random homozygous knockout (RHKO) is an antisense RNA strategy capable of
      identifying genes whose homozygous functional inactivation yields a selectable
      phenotype in cells growing in culture. Using this approach, we isolated NIH 3T3
      fibroblast clones that showed the ability to form colonies on 0.5% agar and
      tumors in nude mice. The gene inactivated in one of these clones was found to
      encode VASP (vasodilator-stimulated phosphoprotein), a previously identified
      protein that binds to components of the cadherin-catenin junctional complex and
      has been implicated in cell-cell interactions, the formation of actin filaments,
      and the transmission of signals at the cytoskeleton-membrane interface.
      Fibroblasts made deficient in VASP by RHKO showed loss of contact inhibition, and
      consequently, continued cell division past confluence. Restoration of VASP
      function by reversal of RHKO yielded cells that had lost the neoplastic
      capabilities acquired during RHKO. Overproduction of VASP mRNA in the sense or
      antisense orientation from expression constructs introduced by transfection into
      naive NIH 3T3 fibroblasts also resulted in neoplastic transformation, implying
      that normal cell growth may require the maintenance of VASP expression within a
      narrow range. Our results implicate VASP in tumorigenesis and/or cancer
      progression.

PMID- 10207094
TI  - Transcription factor E2F-1 is upregulated in response to DNA damage in a manner
      analogous to that of p53.
AB  - The transcription factor E2F-1 directs the expression of genes that induce or
      regulate cell division, and a role for E2F-1 in driving cells into apoptosis is
      the subject of intense discussion. Recently it has been shown that E2F-1 binds
      and coprecipitates with the mouse double-minute chromosome 2 protein (Mdm2). A
      domain of E2F-1 (amino acids 390 to 406) shows striking similarity to the Mdm2
      binding domain of the tumor suppressor protein p53. It is known that interaction
      of Mdm2 with p53 through this domain is required for Mdm2-dependent degradation
      of p53. We show here that E2F-1 protein is upregulated in response to DNA damage.
      The kinetics of induction are dependent upon the source of DNA damage, i.e., fast
      and transient after irradiation with X rays and delayed and stable after
      irradiation with UVC, and thus match the kinetics of p53 induction in response to
      DNA damage. We show further that E2F-1 is also upregulated by treatment with the
      transcription inhibitor actinomycin D and with the kinase inhibitor DRB, as well
      as by high concentrations of the kinase inhibitor H7, all conditions which also
      upregulate p53. In our experiments we were not able to see an increase in E2F-1
      RNA production but did find an increase in protein stability in UVC-irradiated
      cells. Upregulation of E2F-1 in response to DNA damage seems to require the
      presence of wild-type p53, since we did not observe an increase in the level of
      E2F-1 protein in several cell lines which possess mutated p53. Previous
      experiments showed that p53 is upregulated after microinjection of an antibody
      which binds to a domain of Mdm2 that is required for the interaction of Mdm2 with
      p53. Microinjection of the same antibody also increases the expression of E2F-1
      protein, while microinjection of a control antibody does not. Furthermore,
      microinjection of Mdm2 antisense oligonucleotides upregulates E2F-1 protein,
      while microinjection of an unrelated oligonucleotide does not. These data suggest
      that E2F-1 is upregulated in a similar way to p53 in response to DNA damage and
      that Mdm2 appears to play a major role in this pathway.

PMID- 10207095
TI  - The chicken beta-globin 5'HS4 boundary element blocks enhancer-mediated
      suppression of silencing.
AB  - A constitutive DNase I-hypersensitive site 5' of the chicken beta-globin locus,
      termed 5'HS4 or cHS4, has been shown to insulate a promoter from the effect of an
      upstream enhancer and to reduce position effects on mini-white expression in
      Drosophila cells; on the basis of these findings, it has been designated a
      chromatin insulator. We have examined the effect of the cHS4 insulator in a
      system that assays both the level of gene expression and the rate of
      transcriptional silencing. Because transgenes flanked by insulator elements are
      shielded from position effects in Drosophila cells, we tested the ability of cHS4
      to protect transgenes from position effects in mammalian cells. Flanking of an
      expression vector with the cHS4 insulator in a colony assay did not increase the
      number of G418-resistant colonies. Using lox/cre-based recombinase-mediated
      cassette exchange to control integration position, we studied the effect of cHS4
      on the silencing of an integrated beta-geo reporter at three genomic sites in
      K562 erythroleukemia cells. In this assay, enhancers act to suppress silencing
      but do not increase expression levels. While cHS4 blocked enhancement at each
      integration site, the strength of the effect varied from site to site.
      Furthermore, at some sites, cHS4 inhibited the enhancer effect either when placed
      between the enhancer and the promoter or when placed upstream of the enhancer.
      These results suggest that the activity of cHS4 is not dominant in all contexts
      and is unlikely to prevent silencing at all genomic integration sites.

PMID- 10207096
TI  - Distinct mechanisms of activation of Stat1 and Stat3 by platelet-derived growth
      factor receptor in a cell-free system.
AB  - Ligand-dependent activation of the platelet-derived growth factor receptor
      (PDGFR) in fibroblasts in culture leads to the activation of the JAK family of
      protein-tyrosine kinases and of the transcription factors Stat1 and Stat3. To
      determine the biochemical mechanism of STAT activation by PDGFR, we devised a
      cell-free system composed of a membrane fraction from cells overexpressing PDGFR.
      When supplemented with crude cytosol, the membrane fraction supported PDGF- and
      ATP-dependent activation of both Stat1 and Stat3. However, the extent of Stat3
      activation differed depending on the source of the cytosolic fraction. Using
      purified recombinant STAT proteins produced in Escherichia coli, we found that
      Stat1 could be activated by immunopurified PDGFR and showed no additional
      requirement for membrane- or cytosol-derived proteins. In contrast, activation of
      Stat3 exhibited a strong requirement for the cytosolic fraction. The activity
      present in the cytosolic fraction could be depleted with antibodies to JAK
      proteins. We conclude that the mechanisms of activation of Stat1 and Stat3 by
      PDGFR are distinct. Stat1 activation appears to result from a direct interaction
      with the receptor, whereas Stat3 activation additionally requires JAK proteins.

PMID- 10207097
TI  - Activation of somatostatin receptor II expression by transcription factors MIBP1
      and SEF-2 in the murine brain.
AB  - Somatostatin receptor type II expression in the mammalian brain displays a
      spatially and temporally very restricted pattern. In an investigation of the
      molecular mechanisms controlling these patterns, we have recently shown that
      binding of the transcription factor SEF-2 to a novel initiator element in the
      SSTR-2 promoter is essential for SSTR-2 gene expression. Further characterization
      of the promoter identified a species-conserved TC-rich enhancer element. By
      screening a mouse brain cDNA expression library, we cloned a cDNA encoding the
      transcription factor MIBP1. MIBP1 interacts specifically with both the TC box in
      the SSTR-2 promoter and with the SEF-2 initiator-binding protein to enhance
      transcription from the basal SSTR-2 promoter. We then investigated SSTR-2, SEF-2,
      and MIBP1 mRNA expression patterns in the developing and adult murine brain by
      Northern blotting and in situ hybridization. While SEF-2 is widely expressed in
      many neuronal and nonneuronal tissues, MIBP1 expression overlapped precisely with
      expression of SSTR-2 in the frontal cortex and hippocampus. In summary, our data
      for the first time define a regulatory role for the transcription factor MIBP1 in
      mediating spatially and temporally regulated SSTR-2 expression in the brain.

PMID- 10207098
TI  - Role for Hsp90-associated cochaperone p23 in estrogen receptor signal
      transduction.
AB  - The mechanism of signal transduction by the estrogen receptor (ER) is complex and
      not fully understood. In addition to the ER, a number of accessory proteins are
      apparently required to efficiently transduce the steroid hormone signal. In the
      absence of estradiol, the ER, like other steroid receptors, is complexed with
      Hsp90 and other molecular chaperone components, including an immunophilin, and
      p23. This Hsp90-based chaperone complex is thought to repress the ER's
      transcriptional regulatory activities while maintaining the receptor in a
      conformation that is competent for high-affinity steroid binding. However, a role
      for p23 in ER signal transduction has not been demonstrated. Using a mutant ER
      (G400V) with decreased hormone binding capacity as a substrate in a dosage
      suppression screen in yeast cells (Saccharomyces cerevisiae), we identified the
      yeast homologue of the human p23 protein (yhp23) as a positive regulator of ER
      function. Overexpression of yhp23 in yeast cells increases ER transcriptional
      activation by increasing estradiol binding in vivo. Importantly, the magnitude of
      the effect of yhp23 on ER transcriptional activation is inversely proportional to
      the concentration of both ER and estradiol in the cell. Under conditions of high
      ER expression, ER transcriptional activity is largely independent of yhp23,
      whereas at low levels of ER expression, ER transcriptional activation is
      primarily dependent on yhp23. The same relationship holds for estradiol levels.
      We further demonstrate that yhp23 colocalizes with the ER in vivo. Using a yhp23
      green fluorescent protein fusion protein, we observed a redistribution of yhp23
      from the cytoplasm to the nucleus upon coexpression with ER. This nuclear
      localization of yhp23 was reversed by the addition of estradiol, a finding
      consistent with yhp23's proposed role as part of the aporeceptor complex.
      Expression of human p23 in yeast partially complements the loss of yhp23 function
      with respect to ER signaling. Finally, ectopic expression of human p23 in MCF-7
      breast cancer cells increases both hormone-dependent and hormone-independent
      transcriptional activation by the ER. Together, these results strongly suggest
      that p23 plays an important role in ER signal transduction.

PMID- 10207099
TI  - ADD1/SREBP-1c is required in the activation of hepatic lipogenic gene expression
      by glucose.
AB  - The transcription of genes encoding proteins involved in the hepatic synthesis of
      lipids from glucose is strongly stimulated by carbohydrate feeding. It is now
      well established that in the liver, glucose is the main activator of the
      expression of this group of genes, with insulin having only a permissive role.
      While ADD1/SREBP-1 has been implicated in lipogenic gene expression through
      temporal association with food intake and ectopic gain-of-function experiments,
      no genetic evidence for a requirement for this factor in glucose-mediated gene
      expression has been established. We show here that the transcription of
      ADD1/SREBP-1c in primary cultures of hepatocytes is controlled positively by
      insulin and negatively by glucagon and cyclic AMP, establishing a link between
      this transcription factor and carbohydrate availability. Using adenovirus
      mediated transfection of a powerful dominant negative form of ADD1/SREBP-1c in
      rat hepatocytes, we demonstrate that this factor is absolutely necessary for the
      stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl
      coenzyme A carboxylase gene expression. These results demonstrate that ADD1/SREBP
      1c plays a crucial role in mediating the expression of lipogenic genes induced by
      glucose and insulin.

PMID- 10207100
TI  - TAFII40 protein is encoded by the e(y)1 gene: biological consequences of
      mutations.
AB  - The enhancer of yellow 1 gene, e(y)1, of Drosophila melanogaster has been cloned
      and demonstrated to encode the TAFII40 protein. The e(y)1 gene is expressed in
      females much more strongly than in males due to the accumulation of e(y)1 mRNA in
      the ovaries. Two different e(y)1 mutations have been obtained. The e(y)1(ul)
      mutation, induced by the insertion of Stalker into the coding region, leads to
      the replacement of 25 carboxy-terminal amino acids by 17 amino acids encoded by
      the Stalker sequences and to a decrease of the e(y)1 transcription level. The
      latter is the main cause of dramatic underdevelopment of the ovaries and
      sterility of females bearing the e(y)1 mutation. This follows from the
      restoration of female fertility upon transformation of e(y)1(u1) flies with a
      construction synthesizing the mutant protein. The e(y)1(P1) mutation induced by P
      element insertion into the transcribed nontranslated region of the gene has
      almost no influence on the phenotype of flies. However, in combination with the
      phP1 mutation, which leads to a strong P element-mediated suppression of e(y)1
      transcription, this mutation is lethal. Genetic studies of the e(y)1(u1) mutation
      revealed a sensitivity of the yellow and white expression to the TAFII40/e(y)1
      level. The su(Hw)-binding region, Drosophila insulator, stabilizes the expression
      of the white gene and makes it independent of the e(y)1(u1) mutation.

PMID- 10207101
TI  - The Saccharomyces cerevisiae homologues of endonuclease III from Escherichia
      coli, Ntg1 and Ntg2, are both required for efficient repair of spontaneous and
      induced oxidative DNA damage in yeast.
AB  - Endonuclease III from Escherichia coli is the prototype of a ubiquitous DNA
      repair enzyme essential for the removal of oxidized pyrimidine base damage. The
      yeast genome project has revealed the presence of two genes in Saccharomyces
      cerevisiae, NTG1 and NTG2, encoding proteins with similarity to endonuclease III.
      Both contain the highly conserved helix-hairpin-helix motif, whereas only one
      (Ntg2) harbors the characteristic iron-sulfur cluster of the endonuclease III
      family. We have characterized these gene functions by mutant and enzyme analysis
      as well as by gene expression and intracellular localization studies. Targeted
      gene disruption of NTG1 and NTG2 produced mutants with greatly increased
      spontaneous and hydrogen peroxide-induced mutation frequency relative to the wild
      type, and the mutation response was further increased in the double mutant. Both
      enzymes were found to remove thymine glycol and 2, 6-diamino-4-hydroxy-5-N
      methylformamidopyrimidine (faPy) residues from DNA with high efficiency. However,
      on UV-irradiated DNA, saturating concentrations of Ntg2 removed only half of the
      cytosine photoproducts released by Ntg1. Conversely, 5-hydroxycytosine was
      removed efficiently only by Ntg2. The enzymes appear to have different reaction
      modes, as judged from much higher affinity of Ntg2 for damaged DNA and more
      efficient borhydride trapping of Ntg1 to abasic sites in DNA despite limited DNA
      binding. Northern blot and promoter fusion analysis showed that NTG1 is inducible
      by cell exposure to DNA-damaging agents, whereas NTG2 is constitutively
      expressed. Ntg2 appears to be a nuclear enzyme, whereas Ntg1 was sorted both to
      the nucleus and to the mitochondria. We conclude that functions of both NTG1 and
      NTG2 are important for removal of oxidative DNA damage in yeast.

PMID- 10207102
TI  - Detection of RAG protein-V(D)J recombination signal interactions near the site of
      DNA cleavage by UV cross-linking.
AB  - V(D)J recombination is initiated by double-strand cleavage at recombination
      signal sequences (RSSs). DNA cleavage is mediated by the RAG1 and RAG2 proteins.
      Recent experiments describing RAG protein-RSS complexes, while defining the
      interaction of RAG1 with the nonamer, have not assigned contacts immediately
      adjacent to the site of DNA cleavage to either RAG polypeptide. Here we use UV
      cross-linking to define sequence- and site-specific interactions between RAG1
      protein and both the heptamer element of the RSS and the coding flank DNA. Hence,
      RAG1-DNA contacts span the site of cleavage. We also detect cross-linking of RAG2
      protein to some of the same nucleotides that cross-link to RAG1, indicating that,
      in the binding complex, both RAG proteins are in close proximity to the site of
      cleavage. These results suggest how the heptamer element, the recognition surface
      essential for DNA cleavage, is recognized by the RAG proteins and have
      implications for the stoichiometry and active site organization of the RAG1-RAG2
      RSS complex.

PMID- 10207103
TI  - hSiah2 is a new Vav binding protein which inhibits Vav-mediated signaling
      pathways.
AB  - The hematopoietic proto-oncogene vav has been characterized as a Rac1-GDP/GTP
      exchanger protein which regulates cytoskeletal reorganization as well as
      signaling pathways leading to the activation of stress-activated protein kinases
      (SAPK/JNKs). Furthermore, vav overexpression enhances basal and T-cell receptor
      (TCR)-mediated stimulation of the nuclear factor of activated T cells (NFAT). We
      report here the interaction between Vav and hSiah2, a mammalian homolog of
      Drosophila Seven in absentia (Sina) that has been implicated in R7 photoreceptor
      cell formation during Drosophila eye development via the proteasome degradation
      pathway. Vav and hSiah2 interact in vitro and in vivo and colocalize in the
      cytoplasm of hematopoietic cells. The Src homology domain of Vav and the C
      terminal region of hSiah2 are required for this interaction. We provide evidence
      for a negative regulation by hSiah2 of Vav-induced basal and TCR-mediated NFAT
      dependent transcription. Overexpression of hSiah2 also inhibits the onco-Vav
      induced JNK activation. Although the Vav-interacting domain is located in the C
      terminal portion of hSiah2, the N-terminal region of hSiah2 is necessary for the
      inhibitory role that seems to be independent of the proteasome degradation.

PMID- 10207104
TI  - HERF1, a novel hematopoiesis-specific RING finger protein, is required for
      terminal differentiation of erythroid cells.
AB  - The AML1/core binding factor beta (CBFbeta) transcription factor is essential for
      definitive hematopoiesis; however, the downstream pathways through which it
      functions remain incompletely defined. Using a differential cloning approach to
      define components of this pathway, we have identified a novel gene designated
      HERF1 (for hematopoietic RING finger 1), whose expression during development is
      dependent on the presence of functional AML1/CBFbeta. HERF1 contains a tripartite
      RING finger-B box-alpha-helical coiled-coil domain and a C-terminal region
      homologous to the ret proto-oncogene-encoded finger protein. Expression of HERF1
      during embryogenesis coincides with the appearance of definitive erythropoiesis
      and in adult mice is restricted to erythroid cells, increasing 30-fold during
      terminal differentiation. Importantly, inhibition of HERF1 expression blocked
      terminal erythroid differentiation of the murine erythroleukemia cell line MEL,
      whereas its overexpression induced erythroid maturation. These results suggest an
      important role for this protein in erythropoiesis.

PMID- 10207105
TI  - Insulin-like growth factor I synergizes with interleukin 4 for hematopoietic cell
      proliferation independent of insulin receptor substrate expression.
AB  - In the present study, we investigated the potential role of insulin-like growth
      factor I (IGF-I) receptor (IGF-IR) in cell proliferation by overexpressing it in
      32D myeloid progenitor cells. The overexpression of IGF-IR caused the
      transfectants to proliferate in response to IGF-I in the absence of insulin
      receptor substrate (IRS) expression. The activation of overexpressed wild-type
      IGF-IR, but not that of an ATP-binding mutant of IGF-IR, resulted in the
      increased tyrosine phosphorylation of several intracellular proteins, including
      SHC, Src homology 2-containing inositol-5-phosphatase, protein kinase C-delta,
      and Erk2. Grb2 association with SHC and mitogen-activated protein kinase (MAPK)
      activity was also enhanced in response to IGF-I stimulation. Interestingly, the
      stimulation of the IGF-IR transfectants with interleukin 4 (IL-4) also resulted
      in strong mitogenesis independent of IRS expression. Moreover, IGF-I and/or IL-4
      induced long-term cell growth of the IGF-IR transfectants. IL-4 was able to
      synergize with IGF-I for DNA synthesis, even in the parental 32D cells and a pro
      B-cell line, Baf3, indicating the physiological importance of the two growth
      factors in hematopoietic cell proliferation. IL-4 stimulation of the IGF-IR
      transfectants resulted in enhanced tyrosine phosphorylation of SHC, Erk2, and
      signal transducer and activator of transcription 6 (STAT6) proteins. Both IL-4
      and IGF-I were able to induce c-myc early response gene expression, and this
      expression was maximal in the presence of both factors. Finally, we demonstrated
      that a MAPK kinase inhibitor was able to suppress mitogenesis of the IGF-IR
      transfectants in response to IGF-I and/or IL-4. Together, our results suggest
      that IL-4 synergizes with IGF-I for hematopoietic cell proliferation, likely
      through cross talk between SHC/Grb2/MAPK and STAT6 pathways and through c-myc
      gene up-regulation.

PMID- 10207106
TI  - Isolation of a mammalian homologue of a fission yeast differentiation regulator.
AB  - In the fission yeast Schizosaccharomyces pombe the nrd1(+) gene encoding an RNA
      binding protein negatively regulates the onset of differentiation. Its biological
      role is to block differentiation by repressing a subset of the Ste11-regulated
      genes essential for conjugation and meiosis until the cells reach a critical
      level of nutrient starvation. By using the phenotypic suppression of the S. pombe
      temperature-sensitive pat1 mutant that commits lethal haploid meiosis at the
      restrictive temperature, we have cloned ROD1, a functional homologue of nrd1(+),
      from rat and human cDNA libraries. Like nrd1(+), ROD1 encodes a protein with four
      repeats of typical RNA binding domains, though its amino acid homology to Nrd1 is
      limited. When expressed in the fission yeast, ROD1 behaves in a way that is
      functionally similar to nrd1(+), being able to repress Ste11-regulated genes and
      to inhibit conjugation upon overexpression. ROD1 is predominantly expressed in
      hematopoietic cells or organs of adult and embryonic rat. Like nrd1(+) for
      fission yeast differentiation, overexpressed ROD1 effectively blocks both 12-O
      tetradecanoyl phorbol-13-acetate-induced megakaryocytic and sodium butyrate
      induced erythroid differentiation of the K562 human leukemia cells without
      affecting their proliferative ability. These results suggest a role for ROD1 in
      differentiation control in mammalian cells. We discuss the possibility that a
      differentiation control system found in the fission yeast might well be conserved
      in more complex organisms, including mammals.

PMID- 10207107
TI  - Mitochondrial regulation of cell death: mitochondria are essential for procaspase
      3-p21 complex formation to resist Fas-mediated cell death.
AB  - Death receptor Fas transduces cell death signaling upon stimulation by Fas
      ligand, and this death signaling is mediated by caspase. Recently, we reported
      that the cell cycle regulator p21 interacts with procaspase 3 to resist Fas
      mediated cell death. In the present study, the molecular characterization and
      functional region of the procaspase 3-p21 complex was further investigated. We
      observed the p21 expression in the mitochondrial fraction of HepG2 cells and
      detected Fas-mediated cell death only in the presence of actinomycin D. However,
      mitochondrial-DNA-lacking HepG2 (MDLH) cells showed this effect even in the
      absence of actinomycin D. Both p21 and procaspase 3 were expressed in MDLH cells,
      but the procaspase 3-p21 complex formation was not observed. Interestingly, the
      resistance to Fas-mediated cell death in the MDLH cells without actinomycin D was
      recovered after microinjection of HepG2-derived mitochondria into the MDLH cells.
      We conclude that mitochondria are necessary for procaspase 3-p21 complex
      formation and propose that the mitochondrial role during cell death is not only
      death induction but also death suppression.

PMID- 10207108
TI  - Effects of mutations in DNA repair genes on formation of ribosomal DNA circles
      and life span in Saccharomyces cerevisiae.
AB  - A cause of aging in Saccharomyces cerevisiae is the accumulation of
      extrachromosomal ribosomal DNA circles (ERCs). Introduction of an ERC into young
      mother cells shortens life span and accelerates the onset of age-associated
      sterility. It is important to understand the process by which ERCs are generated.
      Here, we demonstrate that homologous recombination is necessary for ERC
      formation. rad52 mutant cells, defective in DNA repair through homologous
      recombination, do not accumulate ERCs with age, and mutations in other genes of
      the RAD52 class have varying effects on ERC formation. rad52 mutation leads to a
      progressive delocalization of Sir3p from telomeres to other nuclear sites with
      age and, surprisingly, shortens life span. We speculate that spontaneous DNA
      damage, perhaps double-strand breaks, causes lethality in mutants of the RAD52
      class and may be an initial step of aging in wild-type cells.

PMID- 10207109
TI  - Cell cycle arrest and reversion of Ras-induced transformation by a conditionally
      activated form of mitogen-activated protein kinase kinase kinase 3.
AB  - Signal-induced proliferation, differentiation, or stress responses of cells
      depend on mitogen-activated protein kinase (MAPK) cascades, the core modules of
      which consist of members of three successively acting kinase families (MAPK
      kinase kinase [MAP3K], MAPK kinase, and MAPK). It is demonstrated here that the
      MEKK3 kinase inhibits cell proliferation, a biologic response not commonly
      associated with members of the MAP3K family of kinases. A conditionally activated
      form of MEKK3 stably expressed in fibroblasts arrests these cells in early G1.
      MEKK3 critically blocks mitogen-driven expression of cyclin D1, a cyclin which is
      essential for progression of fibroblasts through G1. The MEKK3-induced block of
      cyclin D1 expression and of cell cycle progression may be mediated via p38 MAPK,
      a downstream effector of MEKK3. The MEKK3-mediated block of proliferation also
      reverses Ras-induced cellular transformation, suggesting possible tumor
      suppressing functions for this kinase. Together, these results suggest an
      involvement of the MEKK3 kinase in negative regulation of cell cycle progression,
      and they provide the first insights into biologic activities of this kinase.

PMID- 10207110
TI  - The human DNA ligase III gene encodes nuclear and mitochondrial proteins.
AB  - We provide evidence that the human DNA ligase III gene encodes a mitochondrial
      form of this enzyme. First, the DNA ligase III cDNA contains an in-frame ATG
      located upstream from the putative translation initiation start site. The DNA
      sequence between these two ATG sites encodes an amphipathic helix similar to
      previously identified mitochondrial targeting peptides. Second, recombinant green
      fluorescent protein harboring this sequence at its amino terminus was efficiently
      targeted to the mitochondria of Cos-1 monkey kidney cells. In contrast, native
      green fluorescent protein distributed to the cytosol. Third, a series of
      hemagglutinin-DNA ligase III minigene constructs were introduced into Cos-1
      cells, and immunocytochemistry was used to determine subcellular localization of
      the epitope-tagged DNA ligase III protein. These experiments revealed that
      inactivation of the upstream ATG resulted in nuclear accumulation of the DNA
      ligase III protein, whereas inactivation of the downstream ATG abolished nuclear
      localization and led to accumulation within the mitochondrial compartment.
      Fourth, mitochondrial protein extracts prepared from human cells overexpressing
      antisense DNA ligase III mRNA possessed substantially less DNA ligase activity
      than did mitochondrial extracts prepared from control cells. DNA end-joining
      activity was also substantially reduced in extracts prepared from antisense mRNA
      expressing cells. From these results, we conclude that the human DNA ligase III
      gene encodes both nuclear and mitochondrial enzymes. DNA ligase plays a central
      role in DNA replication, recombination, and DNA repair. Thus, identification of a
      mitochondrial form of this enzyme provides a tool with which to dissect mammalian
      mitochondrial genome dynamics.

PMID- 10207111
TI  - Requirement for the kinase activity of human DNA-dependent protein kinase
      catalytic subunit in DNA strand break rejoining.
AB  - The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is an enormous,
      470-kDa protein serine/threonine kinase that has homology with members of the
      phosphatidylinositol (PI) 3-kinase superfamily. This protein contributes to the
      repair of DNA double-strand breaks (DSBs) by assembling broken ends of DNA
      molecules in combination with the DNA-binding factors Ku70 and Ku80. It may also
      serve as a molecular scaffold for recruiting DNA repair factors to DNA strand
      breaks. This study attempts to better define the role of protein kinase activity
      in the repair of DNA DSBs. We constructed a contiguous 14-kb human DNA-PKcs cDNA
      and demonstrated that it can complement the DNA DSB repair defects of two mutant
      cell lines known to be deficient in DNA-PKcs (M059J and V3). We then created
      deletion and site-directed mutations within the conserved PI 3-kinase domain of
      the DNA-PKcs gene to test the importance of protein kinase activity for DSB
      rejoining. These DNA-PKcs mutant constructs are able to express the protein but
      fail to complement the DNA DSB or V(D)J recombination defects of DNA-PKcs mutant
      cells. These results indicate that the protein kinase activity of DNA-PKcs is
      essential for the rejoining of DNA DSBs in mammalian cells. We have also
      determined a model structure for the DNA-PKcs kinase domain based on comparisons
      to the crystallographic structure of a cyclic AMP-dependent protein kinase. This
      structure gives some insight into which amino acid residues are crucial for the
      kinase activity in DNA-PKcs.

PMID- 10207112
TI  - Distinct regulation of p53 and p73 activity by adenovirus E1A, E1B, and E4orf6
      proteins.
AB  - Multiple adenovirus (Ad) early proteins have been shown to inhibit transcription
      activation by p53 and thereby to alter its normal biological functioning. Since
      these Ad proteins affect the activity of p53 via different mechanisms, we
      examined whether this inhibition is target gene specific. In addition, we
      analyzed whether the same Ad early proteins have a comparable effect on
      transcription activation by the recently identified p53 homologue p73. Our
      results show that the large E1B proteins very efficiently inhibited the activity
      of p53 on the Bax, p21(Waf1), cyclin G, and MDM2 reporter constructs but had no
      effect on the activation of the same reporter constructs by p73, with the
      exception of some inhibition of the Bax promoter by Ad12 E1B. The repressive
      effect of the E1A proteins on p53 activity is less than that seen with the large
      E1B proteins, but the E1A proteins inhibit the activity of both p53 and p73. We
      could not detect significant inhibition of p53 functions by E4orf6, but a clear
      repression of the transcription activation by p73 by this Ad early protein was
      observed. In addition, we found that stable expression of the Ad5 E1A and that of
      the E1B protein both caused increased p73 protein expression. The large E1B and
      the E4orf6 proteins together do not target the p73 protein for rapid degradation
      after adenoviral infection, as has previously been found for the p53 protein,
      probably because the large E1B protein does not interact with p73. Our results
      suggest that the p53 and p73 proteins are both inactivated after Ad infection and
      transformation but via distinct mechanisms.

PMID- 10207113
TI  - Molecular determinants of the estrogen receptor-coactivator interface.
AB  - Transcriptional activation by the estrogen receptor is mediated through its
      interaction with coactivator proteins upon ligand binding. By systematic
      mutagenesis, we have identified a group of conserved hydrophobic residues in the
      ligand binding domain that are required for binding the p160 family of
      coactivators. Together with helix 12 and lysine 366 at the C-terminal end of
      helix 3, they form a hydrophobic groove that accommodates an LXXLL motif, which
      is essential for mediating coactivator binding to the receptor. Furthermore, we
      demonstrated that the high-affinity binding of motif 2, conserved in the p160
      family, is due to the presence of three basic residues N terminal to the core
      LXXLL motif. The recruitment of p160 coactivators to the estrogen receptor is
      therefore likely to depend not only on the LXXLL motif making hydrophobic
      interactions with the docking surface on the receptor, but also on adjacent basic
      residues, which may be involved in the recognition of charged residues on the
      receptor to allow the initial docking of the motif.

PMID- 10207114
TI  - Sequence-independent assembly of spermatid mRNAs into messenger ribonucleoprotein
      particles.
AB  - During mammalian spermatogenesis, meiosis is followed by a brief period of high
      transcriptional activity. At this time a large amount of mRNA is stored as
      messenger ribonucleoprotein (mRNP) particles. All subsequent processes of sperm
      maturation occur in the complete absence of transcription, primarily using
      proteins which are newly synthesized from these stored mRNAs. By expressing
      transgene mRNAs in the early haploid spermatids of mice, we have investigated the
      sequence requirements for determining whether specific mRNAs in these cells will
      be stored as mRNP particles or be assembled into polysomes. The results suggest
      that mRNAs which are transcribed in spermatids are assembled into mRNP particles
      by a mechanism that acts independently of mRNA sequence. Our findings reveal a
      fundamental similarity between the mechanisms of translational control used in
      spermatogenesis and oogenesis.

PMID- 10207116
TI  - Re: Arsenic - Evidence of Carcinogenicity in Animals.

PMID- 10207117
TI  - Conformation of peroxynitrite: determination by crystallographic analysis.
AB  - Peroxynitrite is an inorganic toxin of biological importance. It is formed in
      vivo from the diffusion-limited reaction of nitrogen monoxide with superoxide.
      Due to the partial double bond between the nitrogen and the first peroxide
      oxygen, peroxynitrite can occur in two conformations, cis and trans. The
      synthesis of tetramethylammonium peroxynitrite in ammonia [Bohle, D. S., et al.
      (1994) J. Am. Chem. Soc. 116, 7423-7424] yields small crystals if the ammonia is
      left to evaporate slowly. X-ray structure analysis shows that peroxynitrite
      crystallizes in the cis form, relative to the N-O bond. Crystal twinning or
      disorder prevents the determination of accurate bond lengths and bond angles.
      However, a nearly flat (torsion angle of 22 degrees ) molecule with O=N, N-O, and
      O-O bond lengths of 1.16, 1.35, and 1.41 A, respectively, would fit the observed
      electron density best. The space group of tetramethylammonium peroxynitrite is
      Pmmn (59), and it has the following unit cell dimensions: a = 7.1778(11) A, b =
      8.6893(13) A, and c = 5.7266(9) A.

PMID- 10207118
TI  - Theoretical study of the SNV reaction of trichloroethylene (TCE) and CH3S- as a
      model for glutathione conjugation of TCE.
AB  - Trichloroethylene (TCE), a major environmental pollutant, is activated to
      mutagenic and nephrotoxic intermediates through a glutathione (GSH) conjugation
      pathway. Three product isomers of GSH-TCE conjugation, having potentially
      different toxicities, are theoretically possible: cis- or trans-S-(1, 2
      dichlorovinyl)glutathione (cis- or trans-1,2-DCVG, respectively) or 2,2-DCVG.
      This study involved application of ab initio molecular orbital theory to
      computing potential energy profiles (PEPs) and predicting product outcome of the
      reaction of CH3S- with TCE as a model for GSH-TCE conjugation in biological
      systems. A goal of this study was to determine the extent to which a body of
      chemical knowledge pertaining to nucleophilic vinylic substitution (SNV)
      reactions, of which the GSH-TCE conjugation is a representative example, is
      relevant to this biological conjugation problem. PEPs were computed for all
      studied species at the HF/6-31+G level of theory; electron correlation effects
      were estimated at the MP2/6-31+G and MP4/6-31+G levels, and the influence of
      solvation was estimated using the PS-GVB solvation model. Multiple proposed
      reaction pathways were considered, including conjugation at the C1 or C2 site on
      TCE, by in-plane (sigma) or out-of-plane (pi) approach of the nucleophile. Some
      aspects of the MP2 and HF PEPs were found to differ significantly. However, on
      the basis of comparison of activation barriers, calculations at all levels of
      theory predict preference for C2 conjugation over C1 conjugation and formation of
      the trans-1,2-DCVM product over the cis-1,2-DCVM product. These predictions are
      consistent with GSH-TCE conjugation results from in vivo experiments. In
      contrast, relative product energies appear to be a poor indicator of the product
      outcome for this system. Hence, theoretical consideration of the reaction
      chemistry in the vicinity of the site of nucleophilic addition appears to be
      necessary and sufficient to predict the outcome of the enzyme-mediated GSH-TCE
      conjugation.

PMID- 10207115
TI  - Induction of p21(WAF1/CIP1) and inhibition of Cdk2 mediated by the tumor
      suppressor p16(INK4a).
AB  - The tumor suppressor p16(INK4a) inhibits cyclin-dependent kinases 4 and 6. This
      activates the retinoblastoma protein (pRB) and, through incompletely understood
      events, arrests the cell division cycle. To permit biochemical analysis of the
      arrest, we generated U2-OS osteogenic sarcoma cell clones in which p16
      transcription could be induced. In these clones, binding of p16 to cdk4 and cdk6
      abrogated binding of cyclin D1, p27(KIP1), and p21(WAF1/CIP1). Concomitantly, the
      total cellular level of p21 increased severalfold via a posttranscriptional
      mechanism. Most cyclin E-cdk2 complexes associated with p21 and became inactive,
      expression of cyclin A was curtailed, and DNA synthesis was strongly inhibited.
      Induction of p21 alone, in a sibling clone, to the level observed during p16
      induction substantially reproduced these effects. Overexpression of either cyclin
      E or A prevented p16 from mediating arrest. We then extended these studies to HCT
      116 colorectal carcinoma cells and a p21-null clone derived by homologous
      recombination. In the parental cells, p16 expression also augmented total
      cellular and cdk2-bound p21. Moreover, p16 strongly inhibited DNA synthesis in
      the parental cells but not in the p21-null derivative. These findings indicate
      that p21-mediated inhibition of cdk2 contributes to the cell cycle arrest imposed
      by p16 and is a potential point of cooperation between the p16/pRB and
      p14(ARF)/p53 tumor suppressor pathways.

PMID- 10207119
TI  - Mechanism-based inactivation of cytochromes P450 2B1 and P450 2B6 by n
      propylxanthate.
AB  - n-Propylxanthate (nPX) inactivated the 7-ethoxy-4-(trifluoromethyl)coumarin (7
      EFC) O-deethylation activity of purified, reconstituted rat hepatic P450 2B1 or
      human P450 2B6 in a mechanism-based manner. The inactivation followed pseudo
      first-order kinetics and was entirely dependent on both NADPH and nPX. The
      maximal rate constant for inactivation of P450 2B1 at 30 degrees C was 0.2 min-1.
      The apparent KI was 44 microM, and the half-time for inactivation was 4.1 min.
      Purified, reconstituted human P450 2B6 was also inactivated by nPX with a KI of
      12 microM. The kinactivation for P450 2B6 was 0.06 min-1, and the t1/2 was 11
      min. Incubations of P450 2B1 with nPX and NADPH for 20 min resulted in a 75% loss
      in enzymatic activity and a concurrent 25% loss of the enzyme's ability to form a
      reduced CO complex. Little loss in the absolute spectrum of nPX-inactivated P450
      2B1 was observed. With P450 2B6, an 83% loss in enzymatic activity and a 12% loss
      in the CO-reduced spectra were observed. The extrapolated partition ratio for nPX
      with P450 2B1 was 32. P450 2B1 could be protected from inactivation by nPX by
      adding an alternate substrate to the reaction mixture. Removal of unbound nPX by
      dialysis did not reverse the inactivation. The alternate oxidant iodosobenzene
      was able to partially restore enzymatic activity to nPX-inactivated P450 2B1
      samples. A stoichiometry for labeling of 1.2:1 for binding of radiolabeled nPX
      metabolite to P450 2B1 was seen. These results indicated that nPX inactivated
      P450 2B1 and P450 2B6 in a mechanism-based manner. P450 2B1 was inactivated
      primarily by a nPX reactive intermediate that bound to the apoprotein.

PMID- 10207120
TI  - Assessing the mechanism of metabolism-dependent valproic acid-induced in vitro
      cytotoxicity.
AB  - This study was designed to distinguish and evaluate the contribution of reactive
      metabolite and reactive oxygen species as the mechanism of metabolism-dependent
      valproic acid-induced in vitro cytotoxicity. The involvement of reactive oxygen
      species in the mechanism of in vitro cytotoxicity was examined by the addition of
      a series of antioxidant enzymes and iron chelators to the reaction mixture.
      Addition of catalase to the reaction mixture resulted in a complete prevention of
      valproic acid-induced cytotoxicity. Co-incubation of a cell impermeable iron
      chelator deferoxamine did not effect cytotoxicity, whereas 1,10-phenanthroline, a
      chelator with the ability to traverse cell membranes at low concentrations,
      afforded significant protection against valproic acid-induced cytotoxicity. A
      possible inhibitory effect of catalase and 1,10-phenanthroline on the microsomal
      metabolism of valproic acid was disproved by the quantification of valproic acid
      metabolites in the presence and absence of these compounds. To assess the
      specificity of the mechanism of in vitro valproic acid-induced cytotoxicity,
      prevention of in vitro acetaminophen-induced cytotoxicity by antioxidant enzymes
      and iron chelators was also evaluated. Addition of catalase to the reaction
      mixture in the presence of acetaminophen resulted in a moderate reduction in the
      level of but a lack of complete protection of cytotoxicity. Addition of 1,10
      phenanthroline to the reaction mixture in the presence of acetaminophen did not
      result in a detectable change in acetaminophen-induced cytotoxicity. These data
      suggest the involvement of reactive oxygen species in the mechanism of toxicity
      of valproic acid and perhaps reactive metabolites as the major cause of
      cytotoxicity in the case of acetaminophen in the in vitro model investigated.
      Inhibition of poly(ADP-ribose) polymerase activity by various antagonists
      resulted in complete prevention of valproic acid-induced in vitro cytotoxicity.
      The cytoprotective effects of known poly(ADP-ribose) polymerase antagonists
      implicate poly(ADP-ribose) polymerase in the mechanism of in vitro metabolism
      dependent valproic acid-induced cytotoxicity under these conditions. These
      results further point to nuclear DNA as the intracellular site of insult by the
      generated oxygen radicals. Overall, the data obtained support the hypothesis that
      the metabolism-dependent valproic acid-induced in vitro cytotoxicity is the
      result of generation of hydrogen peroxide in the medium that can readily cross
      cell membranes and subsequently interact intracellularly with iron to produce the
      highly reactive hydroxyl free radicals.

PMID- 10207121
TI  - Synthesis of novel chelating agents and their effect on cadmium decorporation.
AB  - A series of novel dithiocarbamates, disodium salts of N-glucamyl-N-dithiocarboxyl
      amino acids, were synthesized, and their usefullness as an antagonist of cadmium
      intoxication was investigated. These chelating agents were found to be effective
      in both acute and repeated exposure cadmium poisoning. The results showed that
      the cadmium mobilizing properties of disodium N-(2,3,4,5, 6-pentahydroxylhexyl)-N
      dithiocarbamate-L-threoninate and disodium N-(2,3,4,5,6-pentahydroxylhexyl)-N
      dithiocarbamate-L-cysteinate are clearly superior to those of sodium N-(4
      methoxybenzyl)-D-glucamine-N-carbodithioate (MeOBGDTC) revealed in the
      experiments described here. The toxicity of these novel compounds is modest, and
      their effect on the concentrations of essential metal ions in the renal cortex is
      quite small in comparison with that of a group treated with cadmium only. The new
      dithiocarbomates were identified by MS, rather than by elemental analysis, as
      they were extremely hygroscopic.

PMID- 10207122
TI  - Development of a 32P-postlabeling method for the detection of 1, N2
      propanodeoxyguanosine adducts of 2-hexenal in vivo.
AB  - 2-Hexenal is an alpha,beta-unsaturated carbonyl compound which forms cyclic 1,N2
      propano adducts in vitro. The adduct formation in vivo was not reported by others
      to date. Because this type of adduct is considered promutagenic (2-hexenal is
      actually mutagenic and genotoxic) and humans are permanently exposed to this
      compound via vegetarian food, 2-hexenal may play a role in carcinogenicity. To
      improve the cancer risk assessment, we developed a new 32P-postlabeling technique
      for this compound and optimized the different steps of the postlabeling
      procedure. The results of the postlabeling methods are shown. A labeling
      efficiency of 35%, a recovery of 10% for the synthesized standards, and a
      detection limit of three 2-hexenal adducts per 10(8) nucleotides was achieved.
      After gavage of 500 mg/kg of body weight to male Fischer 344 rats, the respective
      DNA adducts were detected in rat liver DNA. With this study, we demonstrate in
      vivo adduct formation of 2-hexenal for the first time. Highest adduct levels were
      found 2 days after gavage, and after 4 days, the level was even higher than after
      1 day. No adducts were detected 8 h after gavage. The respective adducts could
      not be found as a background in tissues of untreated rats or in calf thymus DNA
      at the limit of detection.

PMID- 10207123
TI  - Synthesis of anti-7,8-dihydroxy-9,10-epoxy-7,8,9, 10-tetrahydro-11
      methylbenzo[a]pyrene and its reaction with DNA.
AB  - Substitution of a methyl group in the bay region can enhance the tumorigenicity
      of polycyclic aromatic hydrocarbons such as chrysene, benz[a]anthracene, and
      others. This phenomenon has been related to facile DNA adduct formation of bay
      region diol epoxides with a methyl group and epoxide ring in the same bay. While
      anti-7, 8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene and its DNA
      adduct formation have been studied extensively, it is not known whether a methyl
      substituent in the bay region alters the reactivity of DNA in this system. This
      is of interest because 11-methylbenzo[a]pyrene, which has a bay region methyl
      group, is more tumorigenic than benzo[a]pyrene. To examine the question, we have
      devised and employed an efficient synthesis based on photochemical cyclization,
      and prepared anti-7,8-dihydroxy-9, 10-epoxy-7,8,9,10-tetrahydro-11
      methylbenzo[a]pyrene, the likely ultimate carcinogen of 11-methylbenzo[a]pyrene.
      We have then reacted anti-7,8-dihydroxy-9,10-epoxy-7,8,9, 10-tetrahydro-11
      methylbenzo[a]pyrene with calf thymus DNA and found that it gives three major
      adducts. These were identified as having resulted from cis- and trans-ring
      opening of the (S,R,R, S)-enantiomer and from trans-ring opening of the (R,S,S,
      R)-enantiomer. The standard deoxyguanosine adduct markers were prepared, and
      their structures were tentatively assigned on the basis of their CD and 1H NMR
      spectra. The adduct distribution of anti-7,8-dihydroxy-9,10-epoxy-7,8,9, 10
      tetrahydro-11-methylbenzo[a]pyrene is quite different from that observed in the
      reaction of DNA with the corresponding diol epoxides of benzo[a]pyrene or with 5
      methylchrysene. The heterogeneity of adducts obtained with anti-7,8-dihydroxy
      9,10-epoxy-7,8,9, 10-tetrahydro-11-methylbenzo[a]pyrene thus may be related to
      the enhanced tumorigenicity of 11-methylbenzo[a]pyrene.

PMID- 10207124
TI  - Reactions of dihydrodiol epoxides of 5-methylchrysene and 5, 6-dimethylchrysene
      with DNA and deoxyribonucleotides.
AB  - Both syn and anti dihydrodiol epoxides from 5-methylchrysene (5-MCDE) and 5,6
      dimethylchrysene (5,6-DMCDE) were reacted under the same conditions with native
      DNA, denatured DNA, and purine deoxyribonucleotides, and the products were
      quantified. The extents of reaction with the deoxyribonucleotides were
      consistently greater for 5,6-DMCDE than for 5-MCDE. The yield of adducts in the
      reaction with DNA ranged from being a few-fold to 50-fold greater than those
      found in the corresponding deoxyribonucleotide reactions for both 5-MCDE and 5,6
      DMCDE. The DNA-dependent enhancement of product yield was greater for 5-MCDE than
      for 5,6-DMCDE with a few exceptions among cis and trans deoxyadenosine adducts.
      The most substantial differences in DNA-dependent enhancement were found for
      deoxyguanosine adducts; thus, steric hindrance between the 6-methyl group in the
      5,6-DMCDE and the minor groove in the DNA double helix may account for the
      greater DNA-dependent enhancement found in the 5-MCDE reactions.

PMID- 10207125
TI  - Metabolic activation of dibenzo[a,l]pyrene by human cytochrome P450 1A1 and P450
      1B1 expressed in V79 Chinese hamster cells.
AB  - Metabolic activation of the strongly carcinogenic polycyclic aromatic hydrocarbon
      (PAH) dibenzo[a,l]pyrene (DB[a,l]P) and its trans-8,9-dihydrodiol (trans-8,9
      diol) catalyzed by human cytochromes P450 (P450) 1A1 and 1B1 was investigated.
      DNA binding of DB[a,l]P in mammalian cell lines has previously been shown to be
      preferentially mediated by fjord region DB[a,l]P-11,12-dihydrodiol 13,14-epoxides
      (DB[a,l]PDE). In order to elucidate different capabilities of both P450 enzymes
      for metabolic activation of DB[a, l]P V79 Chinese hamster cells, stably
      expressing human P450s 1A1 or 1B1 have been exposed to the parent PAH or its
      racemic trans-8, 9-diol. For this purpose, synthesis and spectroscopic
      characterization of the trans-DB[a,l]P-8,9-diol and its individual enantiomers
      have been achieved. Both human P450-expressing cell lines were capable of
      transforming DB[a,l]P to its fjord region DB[a, l]PDE, but the extent of
      metabolism to DB[a,l]PDE catalyzed by human P450 1B1 was higher compared to human
      P450 1A1 at all times measured. On the other hand, cytotoxicity studies performed
      with the same incubation systems emerged stronger effects by DB[a,l]P and its
      enantiomeric trans-11,12-diols in human P450 1A1-expressing cells. Both human
      P450 enzymes stereospecifically catalyzed the formation of the (-)-DB[a,l]P-11,12
      diol with R,R-configuration, whereas only the human P450 1A1-expressing cells
      form small amounts of the K-region trans-8,9-diol with high excess of the (+)
      (8R, 9R)-enantiomer. Application of trans-DB[a,l]P-8,9-diol in metabolism studies
      revealed that this compound is converted by human P450s 1A1 and 1B1 to several
      diol phenols and bis-diols. However, and even at concentrations as high as 10
      microM, in both cell lines the trans-DB[a,l]P-8,9-diol showed no cytotoxicity at
      all, suggesting that an activation of DB[a,l]P via further oxidation of the K
      region trans-8,9-diol plays a minor role.

PMID- 10207126
TI  - Prooxidant activity of ferrioxamine in isolated rat hepatocytes and linoleic acid
      micelles.
AB  - The complex iron-desferrioxamine (ferrioxamine) is considered chemically
      unreactive, and not able to participate in redox cycle reactions. Desferrioxamine
      dependent toxicity is, however, described in both human and animal studies. The
      aim of this work was to test the possibility that chelated iron, under certain
      circumstances, could enter redox reactions, giving an explanation of
      desferrioxamine side effects. Carefully prepared ferrioxamine, to obtain a 1:1
      desferrioxamine:iron ratio, was added to isolated rat hepatocytes and to linoleic
      acid micelles. A strong prooxidant and cytotoxic effect was observed in the
      cells, also potentiating tert-butyl hydroperoxide-induced lipid peroxidation. In
      micelles, the prooxidant effect was observed only in the presence of ascorbate,
      which is oxidized during the process, giving rise to ascorbyl radical.
      Ferrioxamine, under the experimental conditions used, did not release iron,
      indicating that the prooxidant effect was due to iron redox cycling. The addition
      of desferrioxamine prevented both ferrioxamine- and tert-butyl hydroperoxide
      induced lipid peroxidation and cytotoxicity. Concurrently, a nitroxide radical
      was detected, an indication of the radical scavenger activity of the hydroxamic
      moiety. No radical species was observed when ferrioxamine was added to the same
      system. The prooxidant effect of ferrioxamine gives a possible explanation of the
      reported human and animal desferrioxamine toxicity. When, in compartmentalized
      regions, the ratio of desferrioxamine:metal reaches 1:1, ferrioxamine is formed.
      In the absence of metal-free desferrioxamine, ferrioxamine can participate in
      redox cycling reactions, initiating lipid peroxidation and cytotoxicity.

PMID- 10207127
TI  - In vitro plasmid DNA cleavage by chromium(V) and -(IV) 2-hydroxycarboxylato
      complexes.
AB  - The ability of relatively stable Cr(V) and Cr(IV) complexes with 2
      hydroxycarboxylato ligands [2-ethyl-2-hydroxybutanoate(2-) = ehba; (1R,3R,4R,5R)
      1,3,4,5-tetrahydroxycyclohexanecarboxylate(2-) = quinate = qa] to induce single
      strand breaks in plasmid DNA has been studied under a wide range of reaction
      conditions. The Cr(V) complex, Na[CrVO(ehba)2], causes substantial DNA cleavage
      at pH 4.0-8.0 [[Cr(V)]0 = 0.010-0.75 mM, phosphate buffer, and 37 degrees C]. The
      DNA cleavage is inhibited by the presence of excess ligand, by exclusion of O2,
      or by addition of organic compounds, such as alcohols, carboxylic acids, or DMSO,
      but it is not affected by traces of catalytic metals [Fe(III) or Cu(II)] or by
      addition of catalase. The Cr(IV)-qa complexes, unlike the Cr(V) complexes, are
      able to cleave DNA in the presence of the ligand in a large excess [[Cr(IV)]0 =
      0.50 mM, [qa] = 20-100 mM, pH 3.5-6.0, and 37 degrees C]. This is the first
      direct evidence for DNA cleavage induced by well-characterized Cr(IV) complexes.
      The proposed mechanism for DNA cleavage includes the following: (i) partial
      aquation of the bis-chelated Cr(V) and -(IV) complexes with the formation of
      reactive monochelated forms, (ii) binding of the Cr(V) and -(IV) monochelates to
      the phosphate backbone of DNA, (iii) one- or two-electron oxidations at the
      deoxyribose moieties of DNA by Cr(V) and -(IV), and (iv) cleavage of the
      resulting DNA radicals or cations with or without participation of O2. The
      patterns of DNA damage by Cr(V) and -(IV) can include strand breaks, generation
      of abasic sites, and the formation of Cr(III)-DNA complexes.

PMID- 10207128
TI  - Antioxidant chemistry of green tea catechins. Identification of products of the
      reaction of (-)-epigallocatechin gallate with peroxyl radicals.
AB  - (-)-Epigallocatechin gallate (EGCG), isolated from green tea, displays
      antioxidant properties and is thought to act as an antioxidant in biological
      systems. However, the specific mechanisms of its antioxidant actions remain
      unclear. In this study, we have isolated and identified for the first time two
      reaction products of EGCG derived from its reaction with peroxyl radicals
      generated by thermolysis of the initiator 2,2'-azobis(2,4-dimethylvaleronitrile)
      (AMVN). The products include a seven-membered B-ring anhydride and a novel dimer.
      The identification of these products provides the first unambiguous proof that
      the principal site of antioxidant reactions on the EGCG molecule is the
      trihydroxyphenyl B ring, rather than the 3-galloyl moiety. In contrast to
      phenoxyl radicals from simple phenolic antioxidants, an initially formed EGCG
      phenoxyl radical apparently does not form stable addition products with AMVN
      derived peroxyl radicals. Characteristic reaction products may provide novel
      markers for EGCG antioxidant reactions in living systems.

PMID- 10207129
TI  - Eph receptors and ephrins: effectors of morphogenesis.
AB  - Eph receptor tyrosine kinases and their ligands, the ephrins, appear to lie
      functionally at the interface between pattern formation and morphogenesis. We
      review the role of Eph and ephrin signalling in the formation of segmented
      structures, in the control of axon guidance and cell migration and in the
      development of the vasculature. We address the question of how the specificity of
      response is achieved and discuss the specificity of ephrin-Eph interactions and
      the significance of structural domains in Eph receptors.

PMID- 10207130
TI  - Transcriptional activity of MEF2 during mouse embryogenesis monitored with a MEF2
      dependent transgene.
AB  - The four members of the MEF2 family of MADS-box transcription factors, MEF2-A,
      MEF2-B, MEF2-C and MEF2-D, are expressed in overlapping patterns in developing
      muscle and neural cell lineages during embryogenesis. However, during late fetal
      development and postnatally, MEF2 transcripts are also expressed in a wide range
      of cell types. Because MEF2 expression is controlled by translational and post
      translational mechanisms, it has been unclear whether the presence of MEF2
      transcripts in the embryo reflects transcriptionally active MEF2 proteins. To
      define the temporospatial expression pattern of transcriptionally active MEF2
      proteins during mouse embryogenesis, we generated transgenic mice harboring a
      lacZ reporter gene controlled by three tandem copies of the MEF2 site and
      flanking sequences from the desmin enhancer, which is active in cardiac, skeletal
      and smooth muscle cells. Expression of this MEF2-dependent transgene paralleled
      expression of MEF2 mRNAs in developing myogenic lineages and regions of the adult
      brain. However, it was not expressed in other cell types that express MEF2
      transcripts. Tandem copies of the MEF2 site from the c-jun promoter directed
      expression in a similar pattern to the desmin MEF2 site, suggesting that
      transgene expression reflects the presence of transcriptionally active MEF2
      proteins, rather than other factors specific for DNA sequences flanking the MEF2
      site. These results demonstrate the presence of transcriptionally active MEF2
      proteins in the early muscle and neural cell lineages during embryogenesis and
      argue against the existence of lineage-restricted MEF2 cofactors that
      discriminate between MEF2 sites with different immediate flanking sequences. The
      discordance between MEF2 mRNA expression and MEF2 transcriptional activity in
      nonmuscle cell types of embryos and adults also supports the notion that post
      transcriptional mechanisms regulate the expression of MEF2 proteins.

PMID- 10207131
TI  - A role for serum response factor in coronary smooth muscle differentiation from
      proepicardial cells.
AB  - Coronary artery smooth muscle (SM) cells originate from proepicardial cells that
      migrate over the surface of the heart, undergo epithelial to mesenchymal
      transformation and invade the subepicardial and cardiac matrix. Prior to contact
      with the heart, proepicardial cells exhibit no expression of smooth muscle
      markers including SMalphaactin, SM22alpha, calponin, SMgammaactin or SM-myosin
      heavy chain detectable by RT-PCR or by immunostaining. To identify factors
      required for coronary smooth muscle differentiation, we excised proepicardial
      cells from Hamburger-Hamilton stage-17 quail embryos and examined them ex vivo.
      Proepicardial cells initially formed an epithelial colony that was uniformly
      positive for cytokeratin, an epicardial marker. Transcripts for flk-1, Nkx 2.5,
      GATA4 or smooth muscle markers were undetectable, indicating an absence of
      endothelial, myocardial or preformed smooth muscle cells. By 24 hours,
      cytokeratin-positive cells became SMalphaactin-positive. Moreover, serum response
      factor, undetectable in freshly isolated proepicardial cells, became strongly
      expressed in virtually all epicardial cells. By 72 hours, a subset of epicardial
      cells exhibited a rearrangement of cytoskeletal actin, focal adhesion formation
      and acquisition of a motile phenotype. Coordinately with mesenchymal
      transformation, calponin, SM22alpha and SMgammaactin became expressed. By 5-10
      days, SM-myosin heavy chain mRNA was found, by which time nearly all cells had
      become mesenchymal. RT-PCR showed that large increases in serum response factor
      expression coincide with smooth muscle differentiation in vitro. Two different
      dominant-negative serum response factor constructs prevented the appearance of
      calponin-, SM22alpha- and SMgammaactin-positive cells. By contrast, dominant
      negative serum response factor did not block mesenchymal transformation nor
      significantly reduce the number of cytokeratin-positive cells. These results
      indicate that the stepwise differentiation of coronary smooth muscle cells from
      proepicardial cells requires transcriptionally active serum response factor.

PMID- 10207132
TI  - Prospero distinguishes sibling cell fate without asymmetric localization in the
      Drosophila adult external sense organ lineage.
AB  - The adult external sense organ precursor (SOP) lineage is a model system for
      studying asymmetric cell division. Adult SOPs divide asymmetrically to produce
      IIa and IIb daughter cells; IIa generates the external socket (tormogen) and hair
      (trichogen) cells, while IIb generates the internal neuron and sheath (thecogen)
      cells. Here we investigate the expression and function of prospero in the adult
      SOP lineage. Although Prospero is asymmetrically localized in embryonic SOP
      lineage, this is not observed in the adult SOP lineage: Prospero is first
      detected in the IIb nucleus and, during IIb division, it is cytoplasmic and
      inherited by both neuron and sheath cells. Subsequently, Prospero is
      downregulated in the neuron but maintained in the sheath cell. Loss of prospero
      function leads to 'double bristle' sense organs (reflecting a IIb-to-IIa
      transformation) or 'single bristle' sense organs with abnormal neuronal
      differentiation (reflecting defective IIb development). Conversely, ectopic
      prospero expression results in duplicate neurons and sheath cells and a complete
      absence of hair/socket cells (reflecting a IIa-to-IIb transformation). We
      conclude that (1) despite the absence of asymmetric protein localization,
      prospero expression is restricted to the IIb cell but not its IIa sibling, (2)
      prospero promotes IIb cell fate and inhibits IIa cell fate, and (3) prospero is
      required for proper axon and dendrite morphology of the neuron derived from the
      IIb cell. Thus, prospero plays a fundamental role in establishing binary IIa/IIb
      sibling cell fates without being asymmetrically localized during SOP division.
      Finally, in contrast to previous studies, we find that the IIb cell divides prior
      to the IIa cell in the SOP lineage.

PMID- 10207133
TI  - Antagonistic actions of Arabidopsis cryptochromes and phytochrome B in the
      regulation of floral induction.
AB  - The Arabidopsis photoreceptors cry1, cry2 and phyB are known to play roles in the
      regulation of flowering time, for which the molecular mechanisms remain unclear.
      We have previously hypothesized that phyB mediates a red-light inhibition of
      floral initiation and cry2 mediates a blue-light inhibition of the phyB function.
      Studies of the cry2/phyB double mutant provide direct evidence in support of this
      hypothesis. The function of cryptochromes in floral induction was further
      investigated using the cry2/cry1 double mutants. The cry2/cry1 double mutants
      showed delayed flowering in monochromatic blue light, whereas neither monogenic
      cry1 nor cry2 mutant exhibited late flowering in blue light. This result suggests
      that, in addition to the phyB-dependent function, cry2 also acts redundantly with
      cry1 to promote floral initiation in a phyB-independent manner. To understand how
      photoreceptors regulate the transition from vegetative growth to reproductive
      development, we examined the effect of sequential illumination by blue light and
      red light on the flowering time of plants. We found that there was a light
      quality-sensitive phase of plant development, during which the quality of light
      exerts a profound influence on flowering time. After this developmental stage,
      which is between approximately day-1 to day-7 post germination, plants are
      committed to floral initiation and the quality of light has little effect on the
      flowering time. Mutations in either the PHYB gene or both the CRY1 and CRY2 genes
      resulted in the loss of the light-quality-sensitive phase manifested during
      floral development. The commitment time of floral transition, defined by a
      plant's sensitivity to light quality, coincides with the commitment time of
      inflorescence development revealed previously by a plant's sensitivity to light
      quantity - the photoperiod. Therefore, the developmental mechanism resulting in
      the commitment to flowering appears to be the direct target of the antagonistic
      actions of the photoreceptors.

PMID- 10207134
TI  - Sibling cell fate in the Drosophila adult external sense organ lineage is
      specified by prospero function, which is regulated by Numb and Notch.
AB  - Specification of cell fate in the adult sensory organs is known to be dependent
      on intrinsic and extrinsic signals. We show that the homeodomain transcription
      factor Prospero (Pros) acts as an intrinsic signal for the specification of cell
      fates within the mechanosensory lineage. The sensory organ precursors divide to
      give rise to two secondary progenitors - PIIa and PIIb. Pros is expressed in
      PIIb, which gives rise to the neuron and thecogen cells. Loss of Pros function
      affects the identity of PIIb and neurons fail to differentiate. Pros
      misexpression is sufficient for the transformation of PIIa to PIIb fate. The
      expression of Pros in the normal PIIb cell appears to be regulated by Notch
      signaling.

PMID- 10207135
TI  - Role of vascular endothelial-cadherin in vascular morphogenesis.
AB  - Vascular endothelial (VE)-cadherin is an adhesive transmembrane protein
      specifically expressed at interendothelial junctions. Its extracellular domain
      exhibits Ca2+-dependent homophilic reactivity, promoting cell-cell recognition.
      Mice deficient in VE-cadherin die at mid-gestation resulting from severe vascular
      defects. At the early phases of vascular development (E8.5) of VE-cadherin
      deficient embryos, in situ differentiation of endothelial cells was delayed
      although their differentiation program appeared normal. Vascularization was
      defective in the anterior part of the embryo, while dorsal aortae and vitelline
      and umbilical arteries formed normally in the caudal part. At E9.25, organization
      of endothelial cells into large vessels was incomplete and angiogenesis was
      impaired in mutant embryos. Defects were more severe in extraembryonic
      vasculature. Blood islands of the yolk sac and clusters of angioblasts in
      allantois failed to establish a capillary plexus and remained isolated. This was
      not due to defective cell-cell recognition as endothelial cells formed
      intercellular junctions, as shown by electron microscopy. These data indicate
      that VE-cadherin is dispensable for endothelial homophilic adhesion but is
      required for vascular morphogenesis.

PMID- 10207136
TI  - Intronic enhancers control expression of zebrafish sonic hedgehog in floor plate
      and notochord.
AB  - The signalling molecule Sonic hedgehog (Shh) controls a wide range of
      differentiation processes during vertebrate development. Numerous studies have
      suggested that the absolute levels as well as correct spatial and temporal
      expression of shh are critical for its function. To investigate the regulation of
      shh expression, we have studied the mechanism controlling its spatial expression
      in the zebrafish. We employed an enhancer screening strategy in zebrafish embryos
      based on co-injection of putative enhancer sequences with a reporter construct
      and analysis of mosaic expression in accumulated expression maps. Enhancers were
      identified in intron 1 and 2 that mediate floor plate and notochord expression.
      These enhancers also drive notochord and floor plate expression in the mouse
      embryo strongly suggesting that the mechanisms controlling shh expression in the
      midline are conserved between zebrafish and mouse. Functional analysis in the
      zebrafish embryo revealed that the intronic enhancers have a complex
      organisation. Two activator regions, ar-A and ar-C, were identified in intron 1
      and 2, respectively, which mediate mostly notochord and floor plate expression.
      In contrast, another activating region, ar-B, in intron 1 drives expression in
      the floor plate. Deletion fine mapping of ar-C delineated three regions of 40 bp
      to be essential for activity. These regions do not contain binding sites for
      HNF3beta, the winged helix transcription factor previously implicated in the
      regulation of shh expression, indicating the presence of novel regulatory
      mechanisms. A T-box transcription factor-binding site was found in a functionally
      important region that forms specific complexes with protein extracts from wild
      type but not from notochord-deficient mutant embryos.

PMID- 10207137
TI  - Actomyosin contraction of the posterior hemisphere is required for inversion of
      the Volvox embryo.
AB  - During inversion of a Volvox embryo, a series of cell shape changes causes the
      multicellular sheet to bend outward, and propagation of the bend from the
      anterior to the posterior pole eventually results in an inside-out spherical
      sheet of cells. We use fluorescent and electron microscopy to study the behavior
      of the cytoskeleton in cells undergoing shape changes. Microtubules are aligned
      parallel to the cell's long axis and become elongated in the bend. Myosin and
      actin filaments are arrayed perinuclearly before inversion. In inversion, actin
      and myosin are located in a subnuclear position throughout the uninverted region
      but this localization is gradually lost towards the bend. Actomyosin inhibitors
      cause enlargement of the embryo. The bend propagation is inhibited halfway and,
      as a consequence, the posterior hemisphere remains uninverted. The arrested
      posterior hemisphere will resume and complete inversion even in the presence of
      an actomyosin inhibitor if the anterior hemisphere is removed microsurgically. We
      conclude that the principal role of actomyosin in inversion is to cause a
      compaction of the posterior hemisphere; unless the equatorial diameter of the
      embryo is reduced in this manner, it is too large to pass through the opening
      defined by the already-inverted anterior hemisphere.

PMID- 10207138
TI  - Zebrafish aussicht mutant embryos exhibit widespread overexpression of ace (fgf8)
      and coincident defects in CNS development.
AB  - During the development of the zebrafish nervous system both noi, a zebrafish pax2
      homolog, and ace, a zebrafish fgf8 homolog, are required for development of the
      midbrain and cerebellum. Here we describe a dominant mutation, aussicht (aus), in
      which the expression of noi and ace is upregulated. In aus mutant embryos, ace is
      upregulated at many sites in the embryo, while noi expression is only upregulated
      in regions of the forebrain and midbrain which also express ace. Subsequent to
      the alterations in noi and ace expression, aus mutants exhibit defects in the
      differentiation of the forebrain, midbrain and eyes. Within the forebrain, the
      formation of the anterior and postoptic commissures is delayed and the expression
      of markers within the pretectal area is reduced. Within the midbrain, En and wnt1
      expression is expanded. In heterozygous aus embryos, there is ectopic outgrowth
      of neural retina in the temporal half of the eyes, whereas in putative homozygous
      aus embryos, the ventral retina is reduced and the pigmented retinal epithelium
      is expanded towards the midline. The observation that aus mutant embryos exhibit
      widespread upregulation of ace raised the possibility that aus might represent an
      allele of the ace gene itself. However, by crossing carriers for both aus and
      ace, we were able to generate homozygous ace mutant embryos that also exhibited
      the aus phenotype. This indicated that aus is not tightly linked to ace and is
      unlikely to be a mutation directly affecting the ace locus. However, increased
      Ace activity may underly many aspects of the aus phenotype and we show that the
      upregulation of noi in the forebrain of aus mutants is partially dependent upon
      functional Ace activity. Conversely, increased ace expression in the forebrain of
      aus mutants is not dependent upon functional Noi activity. We conclude that aus
      represents a mutation involving a locus normally required for the regulation of
      ace expression during embryogenesis.

PMID- 10207139
TI  - Macrophages kill capillary cells in G1 phase of the cell cycle during programmed
      vascular regression.
AB  - Programmed capillary regression occurs during normal development of the eye and
      serves as a useful model for assessing the forces that drive vascular involution.
      Using a combination of S-phase labeling and liposome-mediated macrophage
      elimination, we show that during regression, macrophages induce apoptosis of both
      pericytes and endothelial cells in a cell cycle stage-dependent manner. Target
      cells are signaled to die by macrophages approximately 15 hours after S-phase
      labeling and this corresponds to a point in mid-G1 phase of the cell cycle. The
      tight correlation between the restriction point of the cell cycle and the point
      where the macrophage death signal is received suggests that the mitogen, matrix
      and cytoskeletal signals essential for cell-cycle progression may be inhibited by
      macrophages as a means of inducing cell death. Furthermore, these experiments
      show that cells from two distinct lineages are induced to die as a consequence of
      macrophage action, and this provides evidence that macrophage-induced cell death
      may be a general phenomenon during development and homeostasis.

PMID- 10207141
TI  - Control of digit formation by activin signalling.
AB  - Major advances in the genetics of vertebrate limb development have been obtained
      in recent years. However, the nature of the signals which trigger differentiation
      of the mesoderm to form the limb skeleton remains elusive. Previously, we have
      obtained evidence for a role of TGFbeta2 in digit formation. Here, we show that
      activins A and B and/or AB are also signals involved in digit skeletogenesis.
      activin betaA gene expression correlates with the initiation of digit
      chondrogenesis while activin betaB is expressed coincidently with the formation
      of the last phalanx of each digit. Exogenous administration of activins A, B or
      AB into the interdigital regions induces the formation of extra digits.
      follistatin, a natural antagonist of activins, is expressed, under the control of
      activin, peripherally to the digit chondrogenic aggregates marking the
      prospective tendinous blastemas. Exogenous application of follistatin blocks
      physiological and activin-induced digit formation. Evidence for a close
      interaction between activins and other signalling molecules, such as BMPs and
      FGFs, operating at the distal tip of the limb at these stages is also provided.
      Chondrogenesis by activins is mediated by BMPs through the regulation of the BMP
      receptor bmpR-1b and in turn activin expression is upregulated by BMP signalling.
      In addition, AER hyperactivity secondary to Wnt3A misexpression or local
      administration of FGFs, inhibits activin expression. In correlation with the
      restricted expression of activins in the course of digit formation, neither
      activin nor follistatin treatment affects the development of the skeletal
      components of the stylopod or zeugopod indicating that the formation of the limb
      skeleton is regulated by segment-specific chondrogenic signals.

PMID- 10207140
TI  - The smad5 mutation somitabun blocks Bmp2b signaling during early dorsoventral
      patterning of the zebrafish embryo.
AB  - Signaling by members of the TGFbeta superfamily is thought to be transduced by
      Smad proteins. Here, we describe a zebrafish mutant in smad5, designated
      somitabun (sbn). The dominant maternal and zygotic effect of the sbntc24 mutation
      is caused by a change in a single amino acid in the L3 loop of Smad5 protein
      which transforms Smad5 into an antimorphic version, inhibiting wild-type Smad5
      and related Smad proteins. sbn mutant embryos are strongly dorsalized, similarly
      to mutants in Bmp2b, its putative upstream signal. Double mutant analyses and RNA
      injection experiments show that sbn and bmp2b interact and that sbn acts
      downstream of Bmp2b signaling to mediate Bmp2b autoregulation during early
      dorsoventral (D-V) pattern formation. Comparison of early marker gene expression
      patterns, chimera analyses and rescue experiments involving temporally controlled
      misexpression of bmp or smad in mutant embryos reveal three phases of D-V
      patterning: an early sbn- and bmp2b-independent phase when a coarse initial D-V
      pattern is set up, an intermediate sbn- and bmp2b-dependent phase during which
      the putative morphogenetic Bmp2/4 gradient is established, and a later sbn
      independent phase during gastrulation when the Bmp2/4 gradient is interpreted and
      cell fates are specified.

PMID- 10207142
TI  - Spatially restricted expression of PlOtp, a Paracentrotus lividus orthopedia
      related homeobox gene, is correlated with oral ectodermal patterning and skeletal
      morphogenesis in late-cleavage sea urchin embryos.
AB  - Several homeobox genes are expressed in the sea urchin embryo but their roles in
      development have yet to be elucidated. Of particular interest are homologues of
      homeobox genes that in mouse and Drosophila are involved in patterning the
      developing central nervous system (CNS). Here, we report the cloning of an
      orthopedia (Otp)-related gene from Paracentrotus lividus, PlOtp. Otp is a single
      copy zygotic gene that presents a unique and highly restricted expression
      pattern. Transcripts were first detected at the mid-gastrula stage in two pairs
      of oral ectoderm cells located in a ventrolateral position, overlying primary
      mesenchyme cell (PMC) clusters. Increases in both transcript abundance and the
      number of Otp-expressing cells were observed at prism and pluteus stages. Otp
      transcripts are symmetrically distributed in a few ectodermal cells of the oral
      field. Labelled cells were observed close to sites of active skeletal rod growth
      (tips of the budding oral and anal arms), and at the juxtaposition of stomodeum
      and foregut. Chemicals known to perturb PMC patterning along animal-vegetal and
      oral-aboral axes altered the pattern of Otp expression. Vegetalization by LiCl
      caused a shift in Otp-expressing cells toward the animal pole, adjacent to
      shifted PMC aggregates. Nickel treatment induced expression of the Otp gene in an
      increased number of ectodermal cells, which adopted a radialized pattern.
      Finally, ectopic expression of Otp mRNA affected patterning along the oral-aboral
      axis and caused skeletal abnormalities that resembled those exhibited by nickel
      treated embryos. From these results, we conclude that the Otp homeodomain gene is
      involved in short-range cell signalling within the oral ectoderm for patterning
      the endoskeleton of the larva through epithelial-mesenchymal interactions.

PMID- 10207143
TI  - Evidence for collapsin-1 functioning in the control of neural crest migration in
      both trunk and hindbrain regions.
AB  - Collapsin-1 belongs to the Semaphorin family of molecules, several members of
      which have been implicated in the co-ordination of axon growth and guidance.
      Collapsin-1 can function as a selective chemorepellent for sensory neurons,
      however, its early expression within the somites and the cranial neural tube
      (Shepherd, I., Luo, Y. , Raper, J. A. and Chang, S. (1996) Dev. Biol. 173, 185
      199) suggest that it might contribute to the control of additional developmental
      processes in the chick. We now report a detailed study on the expression of
      collapsin-1 as well as on the distribution of collapsin-1-binding sites in
      regions where neural crest cell migration occurs. collapsin-1 expression is
      detected in regions bordering neural crest migration pathways in both the trunk
      and hindbrain regions and a receptor for collapsin-1, neuropilin-1, is expressed
      by migrating crest cells derived from both regions. When added to crest cells in
      vitro, a collapsin-1-Fc chimeric protein induces morphological changes similar to
      those seen in neuronal growth cones. In order to test the function of collapsin-1
      on the migration of neural crest cells, an in vitro assay was used in which
      collapsin-1-Fc was immobilised in alternating stripes consisting of collapsin
      Fc/fibronectin versus fibronectin alone. Explanted neural crest cells derived
      from both trunk and hindbrain regions avoided the collapsin-Fc-containing
      substratum. These results suggest that collapsin-1 signalling can contribute to
      the patterning of neural crest cell migration in the developing chick.

PMID- 10207144
TI  - Expression of Trk receptors in the developing mouse trigeminal ganglion: in vivo
      evidence for NT-3 activation of TrkA and TrkB in addition to TrkC.
AB  - Animals lacking neurotrophin-3 (NT-3) are born with deficits in almost all
      sensory ganglia. Among these, the trigeminal ganglion is missing 70% of the
      normal number of neurons, a deficit which develops during the major period of
      neurogenesis between embryonic stages (E) 10.5 and E13.5. In order to identify
      the mechanisms for this deficit, we used antisera specific for TrkA, TrkB, and
      TrkC to characterize and compare the expression patterns of each Trk receptor in
      trigeminal ganglia of wild type and NT-3 mutants between E10.5 and E15.5.
      Strikingly, TrkA, TrkB, and TrkC proteins appear to be exclusively associated
      with neurons, not precursors. While some neurons show limited co-expression of
      Trk receptors at E11.5, by E13. 5 each neuron expresses only one Trk receptor.
      Neuronal birth dating and cell counts show that in wild-type animals all TrkB-
      and TrkC-expressing neurons are generated before E11.5, while the majority of
      TrkA-expressing neurons are generated between E11.5 and E13.5. In mice lacking NT
      3, the initial formation of the ganglion, as assessed at E10.5, is similar to
      that in wild-type animals. At E11.5, however, the number of TrkC-expressing
      neurons is dramatically reduced and the number of TrkC-immunopositive apoptotic
      profiles is markedly elevated. By E13.5, TrkC-expressing neurons are virtually
      eliminated. At E11.5, compared to wild type, the number of TrkB-expressing
      neurons is also reduced and the number of TrkB immunoreactive apoptotic profiles
      is increased. TrkA neurons are also reduced in the NT-3 mutants, but the major
      deficit develops between E12.5 and E13.5 when elevated numbers of TrkA
      immunoreactive apoptotic profiles are detected. Normal numbers of TrkA- and TrkB
      expressing neurons are seen in a TrkC-deficient mutant. Therefore, our data
      provide evidence that NT-3 supports the survival of TrkA-, TrkB- and TrkC
      expressing neurons in the trigeminal ganglion by activating directly each of
      these receptors in vivo.

PMID- 10207145
TI  - Ectopic expression of individual E(spl) genes has differential effects on
      different cell fate decisions and underscores the biphasic requirement for notch
      activity in wing margin establishment in Drosophila.
AB  - A common consequence of Notch signalling in Drosophila is the transcriptional
      activation of seven Enhancer of split [E(spl)] genes, which encode a family of
      closely related basic-helix-loop-helix transcriptional repressors. Different
      E(spl) proteins can functionally substitute for each other, hampering loss-of
      function genetic analysis and raising the question of whether any specialization
      exists within the family. We expressed each individual E(spl) gene using the GAL4
      UAS system in order to analyse their effect in a number of cell fate decisions
      taking place in the wing imaginal disk. We focussed on sensory organ precursor
      determination, wing vein determination and wing pattern formation. All of the
      E(spl) proteins affect the first two processes in the same way, namely they
      antagonize neural precursor and vein fates. Yet, the efficacy of this antagonism
      is quite distinct: E(spl)mbeta has the strongest vein suppression effect, whereas
      E(spl)m8 and E(spl)m7 are the most active bristle suppressors. During wing
      patterning, Notch activity orchestrates a complex sequence of events that define
      the dorsoventral boundary of the wing. We have discerned two phases within this
      process based on the sensitivity of N loss-of-function phenotypes to concomitant
      expression of E(spl) genes. E(spl) proteins are initially involved in repression
      of the vg quadrant enhancer, whereas later they appear to relay the Notch signal
      that triggers activation of cut expression. Of the seven proteins, E(spl)mgamma
      is most active in both of these processes. In conclusion, E(spl) proteins have
      partially redundant functions, yet they have evolved distinct preferences in
      implementing different cell fate decisions, which closely match their individual
      normal expression patterns.

PMID- 10207146
TI  - Targeted disruption of the homeobox transcription factor Nkx2-3 in mice results
      in postnatal lethality and abnormal development of small intestine and spleen.
AB  - The homeodomain transcription factor Nkx2-3 is expressed in gut mesenchyme and
      spleen of embryonic and adult mice. Targeted inactivation of the Nkx2-3 gene
      results in severe morphological alterations of both organs and early postnatal
      lethality in the majority of homozygous mutants. Villus formation in the small
      intestine appears considerably delayed in Nkx2-3(-)/- foetuses due to reduced
      proliferation of the epithelium, while massively increased growth of crypt cells
      ensues in surviving adult mutants. Interestingly, differentiated cell types of
      the intestinal epithelium are present in homozygous mutants, suggesting that Nkx2
      3 is not required for their cell lineage allocation or migration-dependent
      differentiation. Hyperproliferation of the gut epithelium in adult mutants is
      associated with markedly reduced expression of BMP-2 and BMP-4, suggesting that
      these signalling molecules may be involved in mediating non-cell-autonomous
      control of intestinal cell growth. Spleens of Nkx2-3 mutants are generally
      smaller and contain drastically reduced numbers of lymphatic cells. The white
      pulp appears anatomically disorganized, possibly owing to a homing defect in the
      spleen parenchyme. Moreover, some of the Nkx2-3 mutants exhibit asplenia. Taken
      together these observations indicate that Nkx2-3 is essential for normal
      development and functions of the small intestine and spleen.

PMID- 10207147
TI  - The Caenorhabditis elegans gene ncc-1 encodes a cdc2-related kinase required for
      M phase in meiotic and mitotic cell divisions, but not for S phase.
AB  - We have identified six protein kinases that belong to the family of cdc2-related
      kinases in Caenorhabditis elegans. Results from RNA interference experiments
      indicate that at least one of these kinases is required for cell-cycle
      progression during meiosis and mitosis. This kinase, encoded by the ncc-1 gene,
      is closely related to human Cdk1/Cdc2, Cdk2 and Cdk3 and yeast CDC28/cdc2(+). We
      addressed whether ncc-1 acts to promote passage through a single transition or
      multiple transitions in the cell cycle, analogous to Cdks in vertebrates or
      yeasts, respectively. We isolated five recessive ncc-1 mutations in a genetic
      screen for mutants that resemble larval arrested ncc-1(RNAi) animals. Our results
      indicate that maternal ncc-1 product is sufficient for embryogenesis, and that
      zygotic expression is required for cell divisions during larval development.
      Cells that form the postembryonic lineages in wild-type animals do not enter
      mitosis in ncc-1 mutants, as indicated by lack of chromosome condensation and
      nuclear envelope breakdown. However, progression through G1 and S phase appears
      unaffected, as revealed by expression of ribonucleotide reductase, incorporation
      of BrdU and DNA quantitation. Our results indicate that C. elegans uses multiple
      Cdks to regulate cell-cycle transitions and that ncc-1 is the C. elegans ortholog
      of Cdk1/Cdc2 in other metazoans, required for M phase in meiotic as well as
      mitotic cell cycles.

PMID- 10207148
TI  - The C. elegans homeodomain gene unc-42 regulates chemosensory and glutamate
      receptor expression.
AB  - Genes that specify cell fate can influence multiple aspects of neuronal
      differentiation, including axon guidance, target selection and synapse formation.
      Mutations in the unc-42 gene disrupt axon guidance along the C. elegans ventral
      nerve cord and cause distinct functional defects in sensory-locomotory neural
      circuits. Here we show that unc-42 encodes a novel homeodomain protein that
      specifies the fate of three classes of neurons in the Caenorhabditis elegans
      nervous system: the ASH polymodal sensory neurons, the AVA, AVD and AVE
      interneurons that mediate repulsive sensory stimuli to the nematode head and
      anterior body, and a subset of motor neurons that innervate head and body-wall
      muscles. unc-42 is required for the expression of cell-surface receptors that are
      essential for the mature function of these neurons. In mutant animals, the ASH
      sensory neurons fail to express SRA-6 and SRB-6, putative chemosensory receptors.
      The AVA, AVD and AVE interneurons and RME and RMD motor neurons of unc-42 mutants
      similarly fail to express the GLR-1 glutamate receptor. These results show that
      unc-42 performs an essential role in defining neuron identity and contributes to
      the establishment of neural circuits in C. elegans by regulating the
      transcription of glutamate and chemosensory receptor genes.

PMID- 10207149
TI  - Direct regulatory interaction of the eyeless protein with an eye-specific
      enhancer in the sine oculis gene during eye induction in Drosophila.
AB  - The Pax-6 gene encodes a transcription factor with two DNA-binding domains, a
      paired and a homeodomain, and is expressed during eye morphogenesis and
      development of the nervous system. Pax-6 homologs have been isolated from a wide
      variety of organisms ranging from flatworms to humans. Since loss-of-function
      mutants in insects and mammals lead to an eyeless phenotype and Pax-6 orthologs
      from distantly related species are capable of inducing ectopic eyes in
      Drosophila, we have proposed that Pax-6 is a universal master control gene for
      eye morphogenesis. To determine the extent of evolutionary conservation of the
      eye morphogenetic pathway, we have begun to identify subordinate target genes of
      Pax-6. Previously we have shown that expression of two genes, sine oculis (so)
      and eyes absent (eya), is induced by eyeless (ey), the Pax-6 homolog of
      Drosophila. Here we present evidence from ectopic expression studies in
      transgenic flies, from transcription activation studies in yeast, and from gel
      shift assays in vitro that the EY protein activates transcription of sine oculis
      by direct interaction with an eye-specific enhancer in the long intron of the so
      gene.

PMID- 10207150
TI  - An essential role for the Drosophila Pax2 homolog in the differentiation of adult
      sensory organs.
AB  - The adult peripheral nervous system of Drosophila includes a complex array of
      mechanosensory organs (bristles) that cover much of the body surface of the fly.
      The four cells (shaft, socket, sheath, and neuron) which compose each of these
      organs adopt distinct fates as a result of cell-cell signaling via the Notch (N)
      pathway. However, the specific mechanisms by which these cells execute their
      conferred fates are not well understood. Here we show that D-Pax2, the Drosophila
      homolog of the vertebrate Pax2 gene, has an essential role in the differentiation
      of the shaft cell. In flies bearing strong loss-of-function mutations in the
      shaven function of D-Pax2, shaft structures specifically fail to develop.
      Consistent with this, we find that D-Pax2 protein is expressed in all cells of
      the bristle lineage during the mitotic (cell fate specification) phase of bristle
      development, but becomes sharply restricted to the shaft and sheath cells in the
      post-mitotic (differentiative) phase. Two lines of evidence described here
      indicate that D-Pax2 expression and function is at least in part downstream of
      cell fate specification mechanisms such as N signaling. First, we find that the
      lack of late D-Pax2 expression in the socket cell (the sister of the shaft cell)
      is controlled by N pathway activity; second, we find that loss of D-Pax2 function
      is epistatic to the socket-to-shaft cell fate transformation caused by reduced N
      signaling. Finally, we show that misexpression of D-Pax2 is sufficient to induce
      the production of ectopic shaft structures. From these results, we propose that D
      Pax2 is a high-level transcriptional regulator of the shaft cell differentiation
      program, and acts downstream of the N signaling pathway as a specific link
      between cell fate determination and cell differentiation in the bristle lineage.

PMID- 10207151
TI  - Role of phospholipase Cgamma at fertilization and during mitosis in sea urchin
      eggs and embryos.
AB  - It is well known that stimulation of egg metabolism after fertilization is due to
      a rise in intracellular free calcium concentration. In sea urchin eggs, this
      first calcium signal is followed by other calcium transients that allow
      progression through mitotic control points of the cell cycle of the early embryo.
      How sperm induces these calcium transients is still far from being understood. In
      sea urchin eggs, both InsP3 and ryanodine receptors contribute to generate the
      fertilization calcium transient, while the InsP3 receptor generates the
      subsequent mitotic calcium transients. The identity of the mechanisms that
      generate InsP3 after fertilization remains an enigma. In order to determine
      whether PLCgamma might be the origin of the peaks of InsP3 production that
      punctuate the first mitotic cell cycles of the fertilized sea urchin egg, we have
      amplified by RT-PCR several fragments of sea urchin PLCgamma containing the two
      SH2 domains. The sequence shares similarities with SH2 domains of PLCgamma from
      mammals. One fragment was subcloned into a bacterial expression plasmid and a GST
      fusion protein was produced and purified. Antibodies raised to the GST fusion
      protein demonstrate the presence of PLCgamma protein in eggs. Microinjection of
      the fragment into embryos interferes with mitosis. A related construct made from
      bovine PLCgamma also delayed or prevented entry into mitosis and blocked or
      prolonged metaphase. The bovine construct also blocked the calcium transient at
      fertilization, in contrast to a tandem SH2 control construct which did not
      inhibit either fertilization or mitosis. Our data indicate that PLCgamma plays a
      key role during fertilization and early development.

PMID- 10207152
TI  - beta-catenin signalling modulates proliferative potential of human epidermal
      keratinocytes independently of intercellular adhesion.
AB  - We found that cultured human keratinocytes with high proliferative potential, the
      putative epidermal stem cells, expressed a higher level of noncadherin-associated
      beta-catenin than populations enriched for keratinocytes of lower proliferative
      potential. To investigate the physiological significance of this, a series of
      beta-catenin constructs was introduced into keratinocytes via retroviral
      infection. Full-length beta-catenin and a mutant containing only nine armadillo
      repeats had little effect on proliferative potential in culture, the full-length
      protein being rapidly degraded. However, expression of stabilised, N-terminally
      truncated beta-catenin increased the proportion of putative stem cells to almost
      90% of the proliferative population in vitro without inducing malignant
      transformation, and relieved the differentiation stimulatory effect of
      overexpressing the E-cadherin cytoplasmic domain. Conversely, beta-catenin
      lacking armadillo repeats acted as a dominant negative mutant and stimulated exit
      from the stem cell compartment in culture. The positive and negative effects of
      the beta-catenin mutants on proliferative potential were independent of effects
      on cell-cycle kinetics, overt terminal differentiation or intercellular adhesion,
      and correlated with stimulation or inhibition of transactivation of a TCF/LEF
      reporter in basal keratinocytes. We conclude that the elevated level of
      cytoplasmic beta-catenin in those keratinocytes with characteristics of epidermal
      stem cells contributes to their high proliferative potential.

PMID- 10207153
TI  - Drosophila embryonic pattern repair: how embryos respond to cyclin E-induced
      ectopic division.
AB  - The Drosophila melanogaster embryo ordinarily undergoes thirteen cycles of rapid
      syncytial division followed by three rounds of cellular division for most cells.
      Strict regulation of the number of divisions is believed to be essential for
      normal patterning and development. To determine how the embryo responds to
      hyperplastic growth, we have examined epidermal development in embryos that
      experience additional rounds of mitosis as the result of ectopic Cyclin E
      expression. We observed that the cell density in the epidermis nearly doubled
      within 1 hour of Cyclin E induction. The spacing and width of the ENGRAILED and
      wingless stripes was unchanged, but the cell density within the stripes was
      increased. By 4 hours after Cyclin E induction, the cell density had returned to
      almost normal values. The embryos developed, albeit more slowly, to produce
      viable larvae and adults. The excess cells were removed by apoptosis in a reaper
      dependent fashion as evidenced by increased reaper expression. Embryos lacking
      cell death in the abdomen exhibited changes in ENGRAILED expression. In addition,
      germband retraction and dorsal closure were slower than normal. Ectopic Cyclin E
      expression in cell-death-deficient embryos exacerbated the germband retraction
      and ENGRAILED-expression defects.

PMID- 10207154
TI  - The modulation of DNA content: proximate causes and ultimate consequences.
AB  - The forces responsible for modulating the large-scale features of the genome
      remain one of the most difficult issues confronting evolutionary biology.
      Although diversity in chromosomal architecture, nucleotide composition, and
      genome size has been well documented, there is little understanding of either the
      evolutionary origins or impact of much of this variation. The 80,000-fold
      divergence in genome sizes among eukaryotes represents perhaps the greatest
      challenge for genomic holists. Although some researchers continue to characterize
      much variation in genome size as a mere by-product of an intragenomic selfish DNA
      "free-for-all" there is increasing evidence for the primacy of selection in
      molding genome sizes via impacts on cell size and division rates. Moreover,
      processes inducing quantum or doubling series variation in gametic or somatic
      genome sizes are common. These abrupt shifts have broad effects on phenotypic
      attributes at both cellular and organismal levels and may play an important role
      in explaining episodes of rapid-or even saltational-character state evolution.

PMID- 10207155
TI  - A cluster of ABA-regulated genes on Arabidopsis thaliana BAC T07M07.
AB  - Arabidopsis thaliana BAC T07M07 encoding the abscisic acid-insensitive 4 (ABI4)
      locus has been sequenced completely. It contains a 95,713-bp insert and 24
      predicted genes. Most putative genes were confirmed by gel-based RNA profiling
      and a cluster of ABA-regulated genes was identified. One of the 24 genes,
      designated PP2C5, encodes a putative protein phosphatase 2C. The encoded protein
      was expressed in Escherichia coli, and its enzyme activity in vitro was
      confirmed.

PMID- 10207156
TI  - A genetic linkage map for zebrafish: comparative analysis and localization of
      genes and expressed sequences.
AB  - Genetic screens in zebrafish (Danio rerio) have isolated mutations in hundreds of
      genes with essential functions. To facilitate the identification of candidate
      genes for these mutations, we have genetically mapped 104 genes and expressed
      sequence tags by scoring single-strand conformational polymorphisms in a panel of
      haploid siblings. To integrate this map with existing genetic maps, we also
      scored 275 previously mapped genes, microsatellites, and sequence-tagged sites in
      the same haploid panel. Systematic phylogenetic analysis defined likely mammalian
      orthologs of mapped zebrafish genes, and comparison of map positions in zebrafish
      and mammals identified significant conservation of synteny. This comparative
      analysis also identified pairs of zebrafish genes that appear to be orthologous
      to single mammalian genes, suggesting that these genes arose in a genome
      duplication that occurred in the teleost lineage after the divergence of fish and
      mammal ancestors. This comparative map analysis will be useful in predicting the
      locations of zebrafish genes from mammalian gene maps and in understanding the
      evolution of the vertebrate genome.

PMID- 10207157
TI  - Functional genomics in Caenorhabditis elegans: An approach involving comparisons
      of sequences from related nematodes.
AB  - Comparative genomic analysis was used to investigate the gene structure of the
      bli-4 locus from two related Caenorhabditis species, C. elegans and C. briggsae.
      In C. elegans, bli-4 is a complex gene encoding a member of the kex2/subtilisin
      like family of proprotein convertases. Genomic sequence comparisons coupled with
      RT-PCR analysis identified five additional coding exons that had not been
      identified previously using standard recombinant DNA techniques. The C. briggsae
      gene was able to rescue both viable blistered and developmentally arrested
      mutants of C. elegans bli-4, demonstrating functional conservation. In addition,
      deletion analysis of conserved sequences outside of coding regions, combined with
      phenotypic rescue experiments, identified regulatory elements that alter the
      expression of the bli-4 gene. These results demonstrate the utility of genomic
      sequence comparisons of homologous genes in related species as an effective tool
      with which to dissect the functional information of complex genes.

PMID- 10207158
TI  - A contiguous 3-Mb sequence-ready map in the S3-MX region on 21q22.2 based on high
      throughput nonisotopic library screenings.
AB  - Progress in complete genomic sequencing of human chromosome 21 relies on the
      construction of high-quality bacterial clone maps spanning large chromosomal
      regions. To achieve this goal, we have applied a strategy based on nonradioactive
      hybridizations to contig building. A contiguous sequence-ready map was
      constructed in the Down syndrome congenital heart disease (DS-CHD) region in
      21q22.2, as a framework for large-scale genomic sequencing and positional
      candidate gene approach. Contig assembly was performed essentially by high
      throughput nonisotopic screenings of genomic libraries, prior to clone validation
      by (1) restriction digest fingerprinting, (2) STS analysis, (3) Southern
      hybridizations, and (4) FISH analysis. The contig contains a total of 50 STSs, of
      which 13 were newly isolated. A minimum tiling path (MTP) was subsequently
      defined that consists of 20 PACs, 2 BACs, and 5 cosmids covering 3 Mb between
      D21S3 and MX1. Gene distribution in the region includes 9 known genes (c21-LRP,
      WRB, SH3BGR, HMG14, PCP4, DSCAM, MX2, MX1, and TMPRSS2) and 14 new additional
      gene signatures consisting of cDNA selection products and ESTs. Forthcoming
      genomic sequence information will unravel the structural organization of
      potential candidate genes involved in specific features of Down syndrome
      pathogenesis.

PMID- 10207159
TI  - Panning for genes--A visual strategy for identifying novel gene orthologs and
      paralogs.
AB  - We have developed a rapid visual method for identifying novel members of gene
      families. Starting with an evolutionary tree, 20-50 protein query sequences for a
      gene family are selected from different branches of the tree. These query
      sequences are used to search the GenBank and expressed sequence tag (EST) DNA
      databases and their nightly updates using the tfastx3 or tfasty3 programs. The
      results of all 20-50 searches are collated and resorted to highlight EST or
      genomic sequences that share significant similarity with the query sequences. The
      statistical significance of each DNA/protein alignment is plotted, highlighting
      the portion of the query sequence that is present in the database sequence and
      the percent identity in the aligned region. The collated results for database
      sequences are linked using the WWW to the underlying scores and alignments; these
      links can also be used to perform additional searches to characterize the novel
      sequence further. With traditional "deep" scoring matrices (BLOSUM50) one can
      search for previously unrecognized families of large protein superfamilies.
      Alternatively, by using query sequences and EST libraries from the same species
      (e. g., human or mouse) together with "shallow" scoring matrices and filters that
      remove high-identity sequences, one can highlight new paralogs of previously
      described subfamilies. Using query sequences from the glutathione transferase
      superfamily, we identified two novel mammalian glutathione transferase families
      that were recognized previously only in plants. Using query sequences from known
      mammalian glutathione transferase subfamilies, we identified new candidate
      paralogs from the mouse class-mu, class-pi, and class-theta families.

PMID- 10207160
TI  - Genome-scale cloning and expression of individual open reading frames using
      topoisomerase I-mediated ligation.
AB  - The in vitro cloning of DNA molecules traditionally uses PCR amplification or
      site-specific restriction endonucleases to generate linear DNA inserts with
      defined termini and requires DNA ligase to covalently join those inserts to
      vectors with the corresponding ends. We have used the properties of Vaccinia DNA
      topoisomerase I to develop a ligase-free technology for the covalent joining of
      DNA fragments to suitable plasmid vectors. This system is much more efficient
      than cloning methods that require ligase because the rapid DNA rejoining activity
      of Vaccinia topoisomerase I allows ligation in only 5 min at room temperature,
      whereas the enzyme's high substrate specificity ensures a low rate of vector
      alone transformants. We have used this topoisomerase I-mediated cloning
      technology to develop a process for accelerated cloning and expression of
      individual ORFs. Its suitability for genome-scale molecular cloning and
      expression is demonstrated in this report.

PMID- 10207162
TI  - Transfer of a cathelicidin peptide antibiotic gene restores bacterial killing in
      a cystic fibrosis xenograft model.
AB  - Recent studies suggest that the gene defect in cystic fibrosis (CF) leads to a
      breach in innate immunity. We describe a novel genetic strategy for reversing the
      CF-specific defect of antimicrobial activity by transferring a gene encoding a
      secreted cathelicidin peptide antibiotic into the airway epithelium grown in a
      human bronchial xenograft model. The airway surface fluid (ASF) from CF
      xenografts failed to kill Pseudomonas aeruginosa or Staphylococcus aureus.
      Partial reconstitution of CF transmembrane conductance regulator expression after
      adenovirus-mediated gene transfer restored the antimicrobial activity of ASF from
      CF xenografts to normal levels. Exposure of CF xenografts to an adenovirus
      expressing the human cathelicidin LL-37/hCAP-18 increased levels of this peptide
      in the ASF three- to fourfold above the normal concentrations, which were
      equivalent in ASF from CF and normal xenografts before gene transfer. The
      increase of LL-37 was sufficient to restore bacterial killing to normal levels.
      The data presented describe an alternative genetic approach to the treatment of
      CF based on enhanced expression of an endogenous antimicrobial peptide and
      provide strong evidence that expression of antimicrobial peptides indeed protects
      against bacterial infection.

PMID- 10207161
TI  - Roles of TH1 and TH2 cytokines in a murine model of allergic dermatitis.
AB  - Skin lesions in atopic dermatitis (AD) are characterized by hypertrophy of the
      dermis and epidermis, infiltration by T cells and eosinophils, and expression of
      the cytokines IL-4, IL-5, and IFN-gamma. The role of these cytokines in the
      pathogenesis of AD is not known. We took advantage of a recently described murine
      model of AD elicited by epicutaneous sensitization with ovalbumin (OVA) (1) and
      of the availability of mice with targeted deletions of the IL-4, IL-5, and IFN
      gamma cytokine genes to assess the role of these cytokines in this model.OVA
      sensitized skin from IL-5(-/-) mice had no detectable eosinophils and exhibited
      decreased epidermal and dermal thickening. Sensitized skin from IL-4(-/-) mice
      displayed normal thickening of the skin layers but had a drastic reduction in
      eosinophils and a significant increase in infiltrating T cells. These findings
      were associated with a reduction in eotaxin mRNA and an increase in mRNA for the
      T-cell chemokines macrophage inflammatory protein-2 (MIP-2), MIP-1beta, and
      RANTES. Sensitized skin from IFN-gamma-/- mice was characterized by reduced
      dermal thickening. These results suggest that both the TH2 cytokines IL-4 and IL
      5 and the TH1 cytokine IFN-gamma play important roles in the inflammation and
      hypertrophy of the skin in AD.

PMID- 10207163
TI  - Overexpression of glycine-extended gastrin in transgenic mice results in
      increased colonic proliferation.
AB  - Gastrin is a peptide hormone involved in the growth of both normal and malignant
      gastrointestinal tissue. Recent studies suggest that the glycine-extended
      biosynthetic intermediates mediate many of these trophic effects, but the in vivo
      relevance of glycine-extended gastrin (G-Gly) has not been tested. We have
      generated mice (MTI/G-GLY) that overexpress progastrin truncated at glycine-72 to
      evaluate the trophic effects of G-Gly in an in vivo model. MTI/G-GLY mice have
      elevated serum and colonic mucosal levels of G-Gly compared with wild-type mice.
      MTI/G-GLY mice had a 43% increase in colonic mucosal thickness and a 41% increase
      in the percentage of goblet cells per crypt. MTI/G-GLY mice exhibited increased
      colonic proliferation compared with wild-type controls, with an expansion of the
      proliferative zone into the upper third of the colonic crypts. Continuous
      infusion of G-Gly into gastrin-deficient mice for two weeks also resulted in
      elevated G-Gly levels, a 10% increase in colonic mucosal thickness, and an 81%
      increase in colonic proliferation when compared with gastrin-deficient mice that
      received saline alone. To our knowledge, these studies demonstrate for the first
      time that G-Gly's contribute to colonic mucosal proliferation in vivo.

PMID- 10207164
TI  - Motor neuropathy in porphobilinogen deaminase-deficient mice imitates the
      peripheral neuropathy of human acute porphyria.
AB  - Acute porphyrias are inherited disorders caused by partial deficiency of specific
      heme biosynthesis enzymes. Clinically, porphyrias are manifested by a
      neuropsychiatric syndrome that includes peripheral neuropathy. Although much is
      known about the porphyrias' enzyme defects and their biochemical consequences,
      the cause of the neurological manifestations remains unresolved. We have studied
      porphyric neuropathy in mice with a partial deficiency of porphobilinogen
      deaminase (PBGD). PBGD-deficient mice (PBGD-/-) imitate acute porphyria through
      massive induction of hepatic delta-aminolevulinic acid synthase by drugs such as
      phenobarbital. Here we show that PBGD-/- mice develop impairment of motor
      coordination and muscle weakness. Histologically femoral nerves of PBGD-/- mice
      exhibit a marked decrease in large-caliber (>8 microm) axons and ultrastructural
      changes consistent with primary motor axon degeneration, secondary Schwann cell
      reactions, and axonal regeneration. These findings resemble those found in
      studies of affected nerves of patients with acute porphyria and thus provide
      strong evidence that PBGD deficiency causes degeneration of motor axons without
      signs of primary demyelination, thereby resolving a long-standing controversy.
      Interestingly, the neuropathy in PBGD-/- mice developed chronically and
      progressively and in the presence of normal or only slightly (twofold) increased
      plasma and urinary levels of the putative neurotoxic heme precursor delta
      aminolevulinic acid. These data suggest that heme deficiency and consequent
      dysfunction of hemeproteins can cause porphyric neuropathy.

PMID- 10207165
TI  - PARP alleles within the linked chromosomal region are associated with systemic
      lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by
      various autoantibodies that recognize autoantigens displayed on the surface of
      cells undergoing apoptosis. The genetic contribution to SLE susceptibility has
      been widely recognized. We previously reported evidence for linkage to SLE of the
      human chromosome 1q41-q42 region and have now narrowed it from 15 to 5 cM in an
      extended sample using multipoint linkage analysis. Candidate genes within this
      region include (a) PARP, poly(ADP-ribose) polymerase, encoding a zinc-finger DNA
      binding protein that is involved in DNA repair and apoptosis; (b) TGFB2, encoding
      a transforming growth factor that regulates cellular interactions and responses;
      and (c) HLX1, encoding a homeobox protein that may regulate T-cell development.
      Using a multiallelic, transmission-disequilibrium test (TDT), we found overall
      skewing of transmission of PARP alleles to affected offspring in 124 families (P
      = 0.00008), preferential transmission of a PARP allele to affected offspring (P =
      0.0003), and lack of transmission to unaffected offspring (P = 0.004). Similar
      TDT analyses of TGFB2 and HLX1 polymorphisms yielded no evidence for association
      with SLE. These results suggest that PARP may be (or is close to) the
      susceptibility gene within the chromosome 1q41-q42 region linked to SLE.

PMID- 10207166
TI  - Distinct roles for the small GTPases Cdc42 and Rho in endothelial responses to
      shear stress.
AB  - Shear stress, the tangential component of hemodynamic forces, plays an important
      role in endothelial remodeling. In this study, we investigated the role of Rho
      family GTPases Cdc42 and Rho in shear stress-induced signal transduction and
      cytoskeleton reorganization. Our results showed that shear stress induced the
      translocation of Cdc42 and Rho from cytosol to membrane. Although both Cdc42 and
      Rho were involved in the shear stress-induced transcription factor AP-1 acting on
      the 12-O-tetradecanoyl-13-phorbol-acetate-responsive element (TRE), only Cdc42
      was sufficient to activate AP-1/TRE. Dominant-negative mutants of Cdc42 and Rho,
      as well as recombinant C3 exoenzyme, attenuated the shear stress activation of c
      Jun NH2-terminal kinases (JNKs), suggesting that Cdc42 and Rho regulate the shear
      stress induction of AP-1/TRE activity through JNKs. Shear stress-induced cell
      alignment and stress fiber formation were inhibited by the dominant-negative
      mutants of Rho and p160ROCK, but not by the dominant-negative mutant of Cdc42,
      indicating that the Rho-p160ROCK pathway regulates the cytoskeletal
      reorganization in response to shear stress.

PMID- 10207167
TI  - Defects of T-cell effector function and post-thymic maturation in X-linked hyper
      IgM syndrome.
AB  - X-linked hyper-IgM syndrome (XHIM) results from mutations in the gene encoding
      for CD40 ligand (CD154). Patients with the syndrome suffer from infections with
      opportunistic pathogens such as Cryptosporidium and Pneumocystis carinii. In this
      study, we demonstrate that activated T cells from patients with XHIM produce
      markedly reduced levels of IFN-gamma, fail to induce antigen-presenting cells to
      synthesize IL-12, and induce greatly reduced levels of TNF-alpha. In addition, we
      show that the patients' circulating T lymphocytes of both the CD4(+) and CD8(+)
      subsets contain a markedly reduced antigen-primed population, as determined by
      CD45RO expression. Finally, we demonstrate that the defects in antigen priming
      are likely due to the lack of CD154 expression and insufficient costimulation of
      T cells by CD80/CD86 interactions. Taken together, this study offers a basis for
      the increased susceptibility of patients with XHIM to certain opportunistic
      infections.

PMID- 10207168
TI  - Molecular and functional analysis of SDCT2, a novel rat sodium-dependent
      dicarboxylate transporter.
AB  - Kidney proximal tubule cells take up Krebs cycle intermediates for metabolic
      purposes and for secretion of organic anions through dicarboxylate/organic anion
      exchange. Alteration in reabsorption of citrate is closely related to renal stone
      formation. The presence of distinct types of sodium-coupled dicarboxylate
      transporters has been postulated on either side of the polarized epithelial
      membrane in the kidney proximal tubule. Using a PCR-based approach, we isolated a
      novel member of the sodium-dependent dicarboxylate/sulfate transporter called
      SDCT2. SDCT2 is a 600-amino acid residue protein that has 47-48% amino acid
      identity to SDCT1 and NaDC-1, previously identified in kidney and intestine.
      Northern analysis gave a single band of 3.3 kb for SDCT2 in kidney, liver, and
      brain. In situ hybridization revealed that SDCT2 is prominently expressed in
      kidney proximal tubule S3 segments and in perivenous hepatocytes, consistent with
      the sites of high-affinity dicarboxylate transport identified based on vesicle
      studies. A signal was also detected in the meningeal layers of the brain. SDCT2
      expressed in Xenopus oocytes mediated sodium-dependent transport of di- and
      tricarboxylates with substrate preference for succinate rather than citrate, but
      excluding monocarboxylates. SDCT2, unlike SDCT1, displayed a unique pH dependence
      for succinate transport (optimal pH 7.5-8.5) and showed a high affinity for
      dimethylsuccinate, two features characteristic of basolateral transport. These
      data help to interpret the mechanisms of renal citrate transport, their
      alteration in pathophysiological conditions, and their role in the elimination of
      organic anions and therapeutic drugs.

PMID- 10207169
TI  - Large neutral amino acids block phenylalanine transport into brain tissue in
      patients with phenylketonuria.
AB  - Large neutral amino acids (LNAAs), including phenylalanine (Phe), compete for
      transport across the blood-brain barrier (BBB) via the L-type amino acid carrier.
      Accordingly, elevated plasma Phe impairs brain uptake of other LNAAs in patients
      with phenylketonuria (PKU). Direct effects of elevated brain Phe and depleted
      LNAAs are probably major causes for disturbed brain development and function in
      PKU. Competition for the carrier might conversely be put to use to lower Phe
      influx when the plasma concentrations of all other LNAAs are increased. This
      hypothesis was tested by measuring brain Phe in patients with PKU by quantitative
      1H magnetic resonance spectroscopy during an oral Phe challenge with and without
      additional supplementation with all other LNAAs. Baseline plasma Phe was
      approximately 1,000 micromol/l and brain Phe was approximately 250 micromol/l in
      both series. Without LNAA supplementation, brain Phe increased to approximately
      400 micromol/l after the oral Phe load. Electroencephalogram (EEG) spectral
      analysis revealed acutely disturbed brain activity. With concurrent LNAA
      supplementation, Phe influx was completely blocked and there was no slowing of
      EEG activity. These results are relevant for further characterization of the LNAA
      carrier and of the pathophysiology underlying brain dysfunction in PKU and for
      treatment of patients with PKU, as brain function might be improved by continued
      LNAA supplementation.

PMID- 10207170
TI  - A potential role for protease nexin 1 overexpression in the pathogenesis of
      scleroderma.
AB  - Scleroderma currently affects approximately 75,000-100,000 individuals in the
      United States. Fibroblasts isolated from lesional skin of scleroderma patients
      overexpress collagens and other matrix components, and this abnormality is
      maintained for multiple passages in culture. To understand the molecular basis
      for matrix gene overexpression, we performed a differential display comparison of
      fibroblasts from clinically lesional and nonlesional scleroderma skin. The
      results suggested that protease nexin 1 (PN1), a protease inhibitor, is
      overexpressed in scleroderma fibroblasts. Northern blot verification showed that
      lesional and nonlesional scleroderma fibroblasts had three- to five-fold
      increased levels of PN1 mRNA compared with healthy fibroblasts. Western analysis
      showed that scleroderma fibroblasts also secreted more PN1. In situ hybridization
      of skin biopsy specimens demonstrated PN1 expression in the dermis of four out of
      six scleroderma patients but no PN1 expression in the dermis of six healthy
      volunteers. Transient or stable overexpression of PN1 in mouse 3T3 fibroblasts
      increased collagen promoter activity or endogenous collagen transcript levels,
      respectively. PN1 mutagenized at its active site and antisense PN1 both failed to
      increase collagen promoter activity. These results suggest that overexpression of
      enzymatically active PN1 may play a pathogenic role in the development of the
      scleroderma phenotype.

PMID- 10207171
TI  - Triglyceride enrichment of HDL enhances in vivo metabolic clearance of HDL apo A
      I in healthy men.
AB  - Triglyceride (TG) enrichment of HDL resulting from cholesteryl ester transfer
      protein-mediated exchange with TG-rich lipoproteins may enhance the lipolytic
      transformation and subsequent metabolic clearance of HDL particles in
      hypertriglyceridemic states. The present study investigates the effect of TG
      enrichment of HDL on the clearance of HDL-associated apo A-I in humans. HDL was
      isolated from plasma of six normolipidemic men (mean age: 29.7 +/- 2.7 years) in
      the fasting state and after a five-hour intravenous infusion with a synthetic TG
      emulsion, Intralipid. Intralipid infusion resulted in a 2.1-fold increase in the
      TG content of HDL. Each tracer was then whole-labeled with 125I or 131I and
      injected intravenously into the subject. Apo A-I in TG-enriched HDL was cleared
      26% more rapidly than apo A-I in fasting HDL. A strong correlation between the
      Intralipid-induced increase in the TG content of HDL and the increase in HDL apo
      A-I fractional catabolic rate reinforced the importance of TG enrichment of HDL
      in enhancing its metabolic clearance. HDL was separated further into lipoproteins
      containing apo A-II (LpAI:AII) and those without apo A-II (LpAI). Results
      revealed that the enhanced clearance of apo A-I from TG-enriched HDL could be
      largely attributed to differences in the clearance of LpAI but not LpAI:AII. This
      is, to our knowledge, the first direct demonstration in humans that TG enrichment
      of HDL enhances the clearance of HDL apo A-I from the circulation. This
      phenomenon could provide an important mechanism explaining how HDL apo A-I and
      HDL cholesterol are lowered in hypertriglyceridemic states.

PMID- 10207172
TI  - Perforin-independent beta-cell destruction by diabetogenic CD8(+) T lymphocytes
      in transgenic nonobese diabetic mice.
AB  - Autoimmune diabetes in nonobese diabetic (NOD) mice results from destruction of
      pancreatic beta cells by T lymphocytes. It is believed that CD8(+) cytotoxic T
      lymphocytes (CTLs) effect the initial beta-cell insult in diabetes, but the
      mechanisms remain unclear. Studies of NOD.lpr mice have suggested that disease
      initiation is a Fas-dependent process, yet perforin-deficient NOD mice rarely
      develop diabetes despite expressing Fas. Here, we have investigated the role of
      perforin and Fas in the ability of beta cell-reactive CD8(+) T cells bearing a T
      cell receptor (8.3-TCR) that is representative of TCRs used by CD8(+) CTLs
      propagated from the earliest insulitic lesions of NOD mice, and that targets an
      immunodominant peptide/H-2Kd complex on beta cells, to effect beta-cell damage in
      vitro and in vivo. In vitro, 8.3-CTLs killed antigenic peptide-pulsed non-beta
      cell targets via both perforin and Fas, but they killed NOD beta cells via Fas
      exclusively. Perforin-deficient 8.3-TCR-transgenic NOD mice expressing an
      oligoclonal or monoclonal T-cell repertoire developed diabetes even more
      frequently than their perforin-competent littermates. These results demonstrate
      that diabetogenic CD8(+) CTLs representative of CTLs putatively involved in the
      initiation of autoimmune diabetes kill beta cells in a Fas-dependent and perforin
      independent manner.

PMID- 10207175
TI  - Isolation and purification of a neutral alpha(1,2)-mannosidase from Trypanosoma
      cruzi.
AB  - Trypanosoma cruzi is an obligatory intracellular protozoan parasite that causes
      Chagas' disease in humans. Although a fair amount is known about the biochemistry
      of certain trypanosomes, very little is known about the enzymic complement of
      synthesis and processing of glycoproteins and/or functions of the subcellular
      organelles in this parasite. There have been very few reports on the presence of
      acid and neutral hydrolases in Trypanosoma cruzi. Here we report the first
      purification and characterization of a neutral mannosidase from the epimastigote
      stage of Trypanosoma cruzi. The neutral mannosidase was purified nearly 800-fold
      with an 8% recovery to apparent homogeneity from a CHAPS extract of epimastigotes
      by the following procedures: (1) metal affinity chromatography on Co+2-Sepharose,
      (2) anion exchange, and (3) hydroxylapatite. The purified enzyme has a native
      molecular weight of 150-160 kDa and is apparently composed of two subunits of 76
      kDa. The purified enzyme exhibits a broad pH profile with a maximum at pH 5.9
      6.3. It is inhibited by swainsonine (Ki, 0.1 microM), D-mannono-delta-lactam (Ki,
      20 microM), kifunensine (Ki, 60 microM) but not significantly by
      deoxymannojirimycin. The enzyme is activated by Co2+and Ni2+and strongly
      inhibited by EDTA and Fe2+. The purified enzyme is active against p-nitrophenyl
      alpha-D-mannoside (km = 87 microM). High-mannose Man9GlcNAc substrate was
      hydrolyzed by the purified enzyme to Man7GlcNAc at pH 6.1. The purified enzyme
      does not show activity against alpha1,3- or alpha1,6-linked mannose residues.
      Antibodies against the recently purified lysosomal alpha-mannosidase from T.cruzi
      did not react with the neutral mannosidase reported here.

PMID- 10207174
TI  - Hypoxia induces severe right ventricular dilatation and infarction in heme
      oxygenase-1 null mice.
AB  - Heme oxygenase (HO) catalyzes the oxidation of heme to generate carbon monoxide
      (CO) and bilirubin. CO increases cellular levels of cGMP, which regulates
      vascular tone and smooth muscle development. Bilirubin is a potent antioxidant.
      Hypoxia increases expression of the inducible HO isoform (HO-1) but not the
      constitutive isoform (HO-2). To determine whether HO-1 affects cellular
      adaptation to chronic hypoxia in vivo, we generated HO-1 null (HO-1(-/-)) mice
      and subjected them to hypoxia (10% oxygen) for five to seven weeks. Hypoxia
      caused similar increases in right ventricular systolic pressure in wild-type and
      HO-1(-/-) mice. Although ventricular weight increased in wild-type mice, the
      increase was greater in HO-1(-/-) mice. Similarly, the right ventricles were more
      dilated in HO-1(-/-) mice. After seven weeks of hypoxia, only HO-1(-/-) mice
      developed right ventricular infarcts with organized mural thrombi. No left
      ventricular infarcts were observed. Lipid peroxidation and oxidative damage
      occurred in right ventricular cardiomyocytes in HO-1(-/-), but not wild-type,
      mice. We also detected apoptotic cardiomyocytes surrounding areas of infarcted
      myocardium by terminal deoxynucleotide transferase-mediated dUTP nick end
      labeling (TUNEL) assays. Our data suggest that in the absence of HO-1,
      cardiomyocytes have a maladaptive response to hypoxia and subsequent pulmonary
      hypertension. J.Clin. Invest. 103:R23-R29 (1999).

PMID- 10207173
TI  - Targeted overexpression of elafin protects mice against cardiac dysfunction and
      mortality following viral myocarditis.
AB  - Serine elastases degrade elastin, stimulate vascular smooth muscle cell migration
      and proliferation, and are associated with myocardial damage. To evaluate the
      impact of elastase inhibition on cardiovascular development and disease,
      transgenic mice were created in which the mouse preproendothelin-1 promoter was
      used to target elafin overexpression to the cardiovascular system. To distinguish
      the transgene from endogenous elafin, constructs were made incorporating a FLAG
      sequence; the COOH-terminus FLAG-tagged elafin construct produced a stable,
      functionally active gene product and was used to create transgenic mice.
      Consistent with endothelin expression, abundant elafin mRNA was observed in
      transgenic F1 embryos (embryonic day 13.5) and in adult transgenic mice heart,
      trachea, aorta, kidney, lung, and skin, but not in liver, spleen, and intestine.
      Functional activity of the transgene was confirmed by heightened myocardial
      elastase inhibitory activity. No tissue abnormalities were detected by light
      microscopy or elastin content. However, injection of 10 plaque-forming units
      (PFU) of encephalomyocarditis virus resulted in death within 11 days in 10 out of
      12 nontransgenic mice compared with one out of nine transgenic littermates. This
      reduced mortality was associated with better cardiac function and less myocardial
      inflammatory damage. Thus, elafin expression may confer a protective advantage in
      myocarditis and other inflammatory diseases.

PMID- 10207176
TI  - Recombinant human interleukin-12 is the second example of a C-mannosylated
      protein.
AB  - The beta-chain of human interleukin 12 (IL-12) contains at position 319-322, the
      sequence Trp-x-x-Trp. In human RNase 2 this is the recognition motif for a new,
      recently discovered posttranslational modification, i.e., the C-glycosidic
      attachment of a mannosyl residue to the side chain of tryptophan. Analysis of C
      terminal peptides of recombinant IL-12 (rHuIL-12) by mass spectrometry and NMR
      spectroscopy revealed that Trp-319beta is (partially) C-mannosylated. This
      finding was extended by in vitro mannosylation experiments, using a synthetic
      peptide derived from the same region of the protein as an acceptor. Furthermore,
      human B-lymphoblastoid cells, which secrete IL-12, were found to contain an
      enzyme that carries out the C-mannosylation reaction. This shows that
      nonrecombinant IL-12 is potentially C-mannosylated as well. This is only the
      second report on a C-mannosylated protein. However, the occurrence of the C
      mannosyltransferase activity in a variety of cells and tissues, and the presence
      of the recognition motif in many proteins indicate that more C-mannosylated
      proteins may be found.

PMID- 10207177
TI  - Oligosaccharide analysis and molecular modeling of soluble forms of glycoproteins
      belonging to the Ly-6, scavenger receptor, and immunoglobulin superfamilies
      expressed in Chinese hamster ovary cells.
AB  - Most cell surface molecules are glycoproteins consisting of linear arrays of
      globular domains containing stretches of amino acid sequence with similarities to
      regions in other proteins. These conserved regions form the basis for the
      classification of proteins into superfamilies. Recombinant soluble forms of six
      leukocyte antigens belonging to the Ly-6 (CD59), scavenger receptor (CD5), and
      immunoglobulin (CD2, CD48, CD4, and Thy-1) superfamilies were expressed in the
      same Chinese hamster ovary cell line, thus providing an opportunity to examine
      the extent to which N-linked oligosaccharide processing might vary in a
      superfamily-, domain-, or protein-dependent manner in a given cell. While we
      found no evidence for superfamily-specific modifications of the glycans, marked
      differences were seen in the types of oligosaccharides attached to individual
      proteins within a given superfamily. The relative importance of local protein
      surface properties versus the overall tertiary structure of the molecules in
      directing this protein-specific variation was examined in the context of
      molecular models. These were constructed using the 3D structures of the proteins,
      glycan data from this study, and an oligosaccharide structural database. The
      results indicated that both the overall organization of the domains and the local
      protein structure can have a large bearing on site-specific glycan modification
      of cells in stasis. This level of control ensures that the surface of a single
      cell will display a diverse repertoire of glycans and precludes the presentation
      of multiple copies of a single oligosaccharide on the cell surface. The glycans
      invariably shield large regions of the protein surfaces although, for the
      glycoproteins examined here, these did not hinder the known active sites of the
      molecules. The models also indicated that sugars are likely to play a role in the
      packing of the native cell surface glycoproteins and to limit nonspecific protein
      protein interactions. In addition, glycans located close to the cell membrane are
      likely to affect crucially the orientation of the glycoproteins to which they are
      attached.

PMID- 10207178
TI  - Isolation and structural characterization of glycosphingolipids of in vitro
      propagated human umbilical vein endothelial cells.
AB  - To investigate in detail the expression of glycosphingolipids (GSLs) on
      endothelial cells, 4.85 x 10(9) human umbilical vein endothelial cells (HUVECs)
      were cultivated in a 2 l bioreactor using microcarriers as a support for
      anchorage dependent growing cells. Neutral GSLs and gangliosides were isolated
      and their structures were determined by TLC immunostaining, fast atom bombardment
      mass spectrometry (FAB-MS) of the native GSLs, and gas chromatography-electron
      impact mass spectrometry (GC-EIMS) of partially methylated alditol acetates.
      GbOse4Cer, GbOse3Cer, and LacCer, all carrying mainly C24- and C16-fatty acid
      beside C18-sphingosine, were detected as the major neutral GSLs (36%, 23%, and
      15% of the total orcinol stain, respectively); GlcCer, nLcOse4Cer, and nLcOse6Cer
      were expressed to substantial minor amounts (9%, 12%, and 5% of the total orcinol
      stain, respectively). TLC immunostaining revealed the presence of lipid bound
      Lewisx antigen, whereas the isomeric Lewisa structure was detectable only in very
      low quantities. GM3(Neu5Ac) with C18-sphingosine was the major ganglioside
      constituting about 90% of the whole ganglioside fraction. The fatty acid
      composition was determined by GC-MS of fatty acid methyl esters, indicating the
      predominance of C24- and C16-substituted GM3(Neu5Ac), followed by C18- and C22
      substituted species. Terminally alpha2-3 sialylated neolacto-series ganglioside
      IV3Neu5Ac-nLcOse4Cer was the second most abundant ganglioside in HUVECs (8% of
      the total resorcinol stain), and IV6Neu5Ac-nLcOse4Cer and VI3Neu5Ac-nLcOse6Cer
      (together less than 2% of total resorcinol stain) were found in minor quantities.
      Lipid bound sialyl Lewisx antigen with poly-N-acetyllactosaminyl chains, and
      traces of gangliotetraose-type gangliosides GM1 and GD1a were identified by TLC
      immunostaining. The expression of dominant neutral GSLs LacCer, GbOse3Cer, and
      GbOse4Cer, and of ganglioside GM3(Neu5Ac) was assayed by indirect
      immunofluorescence microscopy of cell layers grown in chamber slides, each
      showing different plasma membrane and subcellular distribution patterns. The
      complete structural characterization of GSLs from HUVECs contributes to our
      understanding about their functional role, not only of the carbohydrate but also
      of the lipid moiety, as receptors for bacterial toxins, as cell surface antigens
      of cellular interaction and as receptors for blood components and macromolecules
      of the extracellular matrix.

PMID- 10207179
TI  - Sequential deglycosylation and utilization of the N-linked, complex-type glycans
      of human alpha1-acid glycoprotein mediates growth of Streptococcus oralis.
AB  - Streptococcus oralis is the agent of a large number of infections in
      immunocompromised patients, but little is known regarding the mechanisms by which
      this fermentative organism proliferates in vivo. Glycoproteins are widespread
      within the circulation and host tissues, and could provide a source of
      fermentable carbohydrate for the growth of those pathogenic organisms with the
      capacity to release monosaccharides from glycans via the production of specific
      glycosidases. The ability of acute phase serum alpha1-acid glycoprotein to
      support growth of S.oralis in vitro has been examined as a model for growth of
      this organism on N-linked glycoproteins. Growth was accompanied by the production
      of a range of glycosidases (sialidase, N-acetyl-beta-D-glucosaminidase, and beta
      D-galactosidase) as measured using the 4-methylumbelliferone-linked substrates.
      The residual glycoprotein glycans remaining during growth of this organism were
      released by treatment with hydrazine and their analysis by HPAEC-PAD and MALDI
      demonstrated extensive degradation of all glycan chains with only terminal N
      acetylglucosamine residues attached to asparagines of the protein backbone
      remaining when growth was complete. Monosaccharides were released sequentially
      from the glycans by S.oralis glycosidases in the order sialic acid, galactose,
      fucose, nonterminal N-acetylglucosamine, and mannose due to the actions of exo
      glycosidic activities, including mannosidases which have not previously been
      reported for S.oralis. All released monosaccharides were metabolized during
      growth with the exception of fucose which remained free in culture supernatants.
      Direct release of oligosaccharides was not observed, indicating the absence of
      endo-glycosidases in S.oralis. We propose that this mechanism of deglycosylation
      of host glycoproteins and the subsequent utilization of released monosaccharides
      is important in the survival and persistence of this and other pathogenic
      bacteria in vivo.

PMID- 10207180
TI  - Purification of CMP-N-acetylneuraminic acid synthetase from bovine anterior
      pituitary glands.
AB  - CMP-beta-N-acetylneuraminic acid (CMP-neuNAc) is the substrate for the
      sialylation of glycoconjugates by sialyltransferases in microbes and higher
      eukaryotes. CMP-neuNAc synthetase catalyzes the formation of this substrate, CMP
      neuNAc, from CTP and neuNAc. In this report we describe the purification of CMP
      neuNAc synthetase from bovine anterior pituitary glands. The enzyme was purified
      by ion exchange, gel filtration, and affinity chromatography. The protein was
      homogeneous on SDS-PAGE with a molecular weight of 52 kDa, a subunit size similar
      to that of the E.coli K1 (48.6 kDa). The identity of the 52 kDa protein band was
      confirmed by native gel electrophoresis in that the position of the enzyme
      activity in gel slices coincided with the position of major bands in the stained
      gel. Photoaffinity labeling with 125I-ASA-CDP ethanolamine resulted in the
      modification of a 52 kDa polypeptide that was partially protected against
      modification by the substrate CTP. Enzyme activity in crude fractions could be
      adsorbed onto an immunoadsorbent prepared from antibody against the purified 52
      kDa protein. Taken together these data suggest that the 52 kDa polypeptide
      purified by this procedure described in this report is indeed CMP-neuNAc
      synthetase. The active enzyme chromatographed on a gel filtration column at 158
      kDa suggesting it exists in its native form as an oligomer.

PMID- 10207181
TI  - Galectin-3 and polarized growth within collagen gels of wild-type and ricin
      resistant MDCK renal epithelial cells.
AB  - Previous studies (Q. Bao and R. C. Hughes (1995) J. Cell Sci., 108, 2791-2800)
      showed that the beta-galactoside-binding protein, galectin-3, is secreted onto
      the basolateral surface domains of Madin-Darby canine kidney MDCK cells growing
      as polarized cysts within a collagen gel. The growth and enlargement of such
      cysts were shown to be increased significantly when cultured in the presence of
      antibodies directed against the lectin and were slowed down by addition of
      exogenous galectin-3. These results suggested a role for galectin-3, interacting
      with appropriately glycosylated surface receptors, as a negative growth regulator
      in the development of MDCK cysts, a well-known model for renal epithelial
      morphogenesis. In the present report we have tested this proposal by use of a
      ricin-resistant mutant of MDCK cells that is unable to transfer galactose
      residues during biosynthesis of cellular glycoconjugates and hence lacks
      extracellular receptors for galectin-3. We find that when grown within collagen
      gels, the mutant cell cysts grow significantly faster than wild-type cell cysts.
      Furthermore, they form nonspherical and tubular cysts that are induced in wild
      type cell cysts only under the influence of the morphogen, hepatocyte growth
      factor (HGF).

PMID- 10207182
TI  - Novel Schizosaccharomyces pombe N-linked GalMan9GlcNAc isomers: role of the Golgi
      GMA12 galactosyltransferase in core glycan galactosylation.
AB  - Schizosaccharomyces pombe synthesizes very large N-linked galactomannans, which
      are elongated from the Man9GlcNAc2 core that remains after the trimming of three
      Glc residues from the Glc3Man9GlcNAc2 originally transferred from dolichyl
      pyrophosphate to nascent proteins in the endoplasmic reticulum. Prior to
      elongation of the galactomannan outer chain, the Man9GlcNAc2 core is modified
      into a family of Hex10-15GlcNAc2 structures by the addition of both Gal and Man
      residues (Ziegler et al. (1994) J. Biol. Chem., 269, 12527-12535). To understand
      the pathway of Man9GlcNAc2 modification, the Hex10GlcNAc-sized pool was isolated
      by Bio-Gel P-4 gel filtration from the endo H-released N-glycans of S.pombe
      glycoproteins. This pool yielded four major fractions, a, b, c, and g, on
      preparative high pH, anion exchange chromatography, that represented 10, 29, 46,
      and 13% of the total Hex10GlcNAc present, respectively. Structures of the glycan
      isomers present in each fraction were determined by one- and two-dimensional 1H
      NMR spectroscopy techniques. Fraction a is principally (approximately 93%) a
      Man10GlcNAc with a new alpha1,2-linked Man cap on the upper-arm of Man9GlcNAc.
      Fraction b contained two isomers of GalMan9GlcNAc in which an alpha1,2-linked
      terminal Gal had been added either to the upper (b1, 30%) or middle-arm (b2, 70%)
      of Man9GlcNAc. The gma12 - alpha1,2-galactosyltransferase-negative S. pombe
      strain (Chappell et al. (1994) Mol. Biol. Cell., 5, 519-528) did not make
      fraction b implying that the gma12p galactosyltransferase is responsible for
      synthesis of both isomers b1 and b2. Isomer c is Man10GlcNAc in which a new
      branching alpha1, 6-linked Man had been added to the lower-arm alpha1,3-linked
      core residue as found earlier in Saccharomyces cerevisiae and Pichia pastoris.
      Fraction g had less than molar stoichiometry of both Gal and Glc. The major
      isomer (g1, 85%) is the Man9GlcNAc core with an alpha1,3-linked branching Gal on
      the penultimate 2-O-substituted Man of the lower arm. This residue is also found
      on a novel O-linked oligosaccharide recently described in S.pombe;
      Manalpha1,2(Galalpha1, 3)Manalpha1,2Mannitol (Gemmill and Trimble (1999)
      Glycobiology, 9, 507-515). The second isomer (g2, 15%) is the partially processed
      Glc2Man9GlcNAc intermediate. Defining these Hex10GlcNAc structures provides a
      starting point for understanding the enzymology of N-linked galactomannan core
      heterogeneity seen on S.pombe glycoproteins.

PMID- 10207183
TI  - Schizosaccharomyces pombe produces novel Gal0-2Man1-3 O-linked oligosaccharides.
AB  - Schizosaccharomyces pombe whole-cell glycoproteins, previously depleted of N
      linked glycans by sequential treatment with endo-ss-N-acetylglucosaminidase H and
      peptide-N4-asparagine amidohydrolase F, were ss-eliminated with 0.1 M NaOH/1 M
      NaBH4 to release the O-linked oligosaccharides. The saccharide-alditols were
      separated by gel-exclusion chromatography into pools from Hexitol to Hex4Hexitol
      in size. Analysis of the Hexitol pool indicated Man to be the only sugar linked
      to Ser or Thr residues. The Hex1Hexitol pool contained two components,
      Galalpha1,2Man-ol (2A) and Manalpha1, 2Man-ol (2B). The Hex2Hexitol pool
      contained two components, Galalpha1,2Manalpha1,2Man-ol (3A) and
      Manalpha1,2Manalpha1,2Man-ol (3B). The two Hex3Hexitol components were
      Galalpha1,2(Galalpha1, 3)Manalpha1,2Man-ol (4A) and
      Manalpha1,2(Galalpha1,3)Manalpha1, 2Man-ol (4B). The Hex4Hexitol component was
      found to be a single isomer with the composition of
      Galalpha1,2(Galalpha1,3)Manalpha1, 2Manalpha1,2Man-ol (5AB). Surprisingly,
      galactobiose was not detected in any of these oligosaccharides. The gma12 (T. G.
      Chappell and G. Warren (1989) J. Cell Biol., 109, 2693-2707) and gth1 (T. G.
      Chappell personal communication) alpha1, 2-galactosyltransferase-deficient
      mutants and the gma12/gth1 double mutant S.pombe strains were similarly examined.
      The results indicated that gma12p is solely responsible for the addition of
      terminal alpha1,2-linked Gal in compound 2A, while one or both of gma12p and
      gth1p are required for the alpha1,2-linked Gal in 4A. Both transferases are
      largely responsible for terminal Gal in isomer 5AB. Neither gma12 nor gth1 had
      any discernible effect on the structure of the large N-linked galactomannans as
      determined by 1H NMR spectroscopy. Thus, while gth1p and gma12p appear
      responsible for adding alpha1,2-linked Gal to terminal Man, neither adds
      galactose side chains to the N-linked poly alpha1,6-Man outerchain, nor the O
      linked branch-forming alpha1,3-linked Gal. Furthermore, the presence of
      Hexalpha1,2(Galalpha1,3)Manalpha1,2- structures in the O-linked glycans implies
      the presence of a novel branch-forming alpha1,3-galactosyltransferase in S.pombe.

PMID- 10207185
TI  - Semi-continuous perfusion system for delivering intermittent physiological
      pressure to regenerating cartilage.
AB  - A semi-continuous compression/perfusion system has been custom made to allow the
      application of intermittent hydrostatic pressure, at physiological levels, to
      regenerating tissues over the long term. To test the system, isolated foal
      chondrocytes were seeded in resorbable polyglycolic acid meshes and cultured in
      the system for 5 weeks. The cell/polymer constructs were subjected to an
      intermittent hydrostatic pressure of 500 psi and were fed semi-continuously.
      Assays of the resulting tissue constructs indicate that the reactor supports
      cartilage development and that physiological intermittent compression enhances
      the production of extracellular matrix by the chondrocytes. The concentrations of
      sulfated glycosaminoglycan were found to be at least twice as high as those in
      control (unpressurized) samples. A correlation between the sulfated
      glycosaminoglycan content and the compressive modulus in pressurized, but not
      control, samples suggests that physiological intermittent pressurization not only
      enhances the production of extracellular matrix but may also influence matrix
      organization resulting in a stronger construct.

PMID- 10207184
TI  - Isolation and characterization of linear polylactosamines containing one and two
      site-specifically positioned Lewis x determinants: WGA agarose chromatography in
      fractionation of mixtures generated by random, partial enzymatic alpha3
      fucosylation of pure polylactosamines.
AB  - We report that isomeric monofucosylhexasaccharides, Galbeta1-4GlcNAcbeta1
      3Galbeta1-4GlcNAcbeta1- 3Galbeta1-4(Fucalpha1-3) GlcNAc, Galbeta1-4GlcNAcbeta1
      3Galbeta1-4(Fucalpha1-3) GlcNAcbeta1-3Galbeta1-4 GlcNAc and Galbeta1-4(Fucalpha1
      3)GlcNAcbeta1-3Galbeta1- 4GlcNAcbeta1-3Galbeta1-4 GlcNAc, and
      bifucosylhexasaccharides Galbeta1-4GlcNAcbeta1-3Galbeta1-4(Fucalpha1-3)
      GlcNAcbeta1-3Galbeta1-4(Fucalpha1-3)GlcNAc, Galbeta1-4(Fucalpha1-3)GlcNAcbeta1
      3Galbeta1- 4GlcNAcbeta1-3Galbeta1-4 (Fucalpha1-3)GlcNAc and Galbeta1-4(Fucalpha1
      3)GlcNAcbeta1-3Galbeta1-4( Fucalpha1-3)GlcNAcbeta1-3Galbeta1-4GlcNAc can be
      isolated in pure form from reaction mixtures of the linear hexasaccharide
      Galbeta1-4GlcNAcbeta1-3Galbeta1-4GlcNAcbeta1- 3Galbeta1-4GlcNAc with GDP-fucose
      and alpha1,3-fucosyltransferases of human milk. The pure isomers were
      characterized in several ways;1H-NMR spectroscopy, for instance, revealed
      distinct resonances associated with the Lewis x group [Galbeta1-4(Fucalpha1
      3)GlcNAc] located at the proximal, middle, and distal positions of the
      polylactosamine chain. Chromatography on immobilized wheat germ agglutinin was
      crucial in the separation process used; the isomers carrying the fucose at the
      reducing end GlcNAc possessed particularly low affinities for the lectin.
      Isomeric monofucosyl derivatives of the pentasaccharides GlcNAcbeta1-3Galbeta1
      4GlcNAcbeta1-3Galbeta1- 4Gl cNAc and Galalpha1-3Galbeta1-4GlcNAcbeta1-3Galbeta1
      4G lcN Ac and the tetrasaccharide Galbeta1-4GlcNAcbeta1-3Galbeta1-4GlcNAc were
      also obtained in pure form, implying that the methods used are widely applicable.
      The isomeric Lewis x glycans proved to be recognized in highly variable binding
      modes by polylactosamine-metabolizing enzymes, e.g., the midchain beta1,6-GlcNAc
      transferase (Leppanen et al., Biochemistry, 36, 13729-13735, 1997).

PMID- 10207186
TI  - Method for automated cartilage histomorphometry.
AB  - We have developed and tested a color-based method for automated computerized
      histomorphometric analysis of cartilage. Histological sections stained with
      safranin O from 29 rabbit periosteal agarose-cultured explants were selected with
      various amounts of cartilage (0-100%). Color photomicrographs of these sections
      were visually assessed by five expert observers who estimated the percent area
      occupied by cartilage and outlined (in pen) the areas they considered to be
      cartilage. Manual histomorphometry was performed by cutting out and weighing the
      outlined areas. The average area for each of the five observers ranged from 31%
      to 43% (intraclass correlation coefficient = 0.70). The average of these values
      was used as a "gold standard" against which to compare the computer measurements.
      When point counting histomorphometry was performed on the 29 sections, the data
      agreed with the measurements made by the other five cartilage experts (r2 = 0.96;
      p < 0.0001). The analysis of cartilage is based on safranin O stain, using a
      custom-designed Vidas 2.1 Image Analysis Program (Zeiss). The computer-based
      results correlated very closely with those obtained by manual (p = 0.0001; r2 =
      0.92) and point counting (r2 = 0.92; p < 0.0001) histomorphometry. The mean
      percentage of the sections occupied by cartilage measured in the automated mode
      was only 6% higher than that using the gold standard. Histological complexity had
      only a minor effect on the computerized values. The automated computerized image
      analysis system has the advantages of objectivity, accuracy, repeatability, and
      ease of use.

PMID- 10207187
TI  - Characterization of the mineral in calcified articular cartilagenous tissue
      formed in vitro.
AB  - Cartilagenous tissue with mineralized and nonmineralized layers was generated in
      vitro using bovine chondrocytes isolated from the deep zone of articular
      cartilage. Mineralization was induced by addition of either beta-glycerophosphate
      (beta-GP), phosphoethanolamine (PEA), or adenosine triphosphate (ATP). As this
      tissue might be suitable for use in joint resurfacing, the mineral of the
      calcified layer was characterized and compared to that present in the in vivo
      mineralized zone of bovine articular cartilage. Von Kossa staining demonstrated
      the presence of mineralization in the lower half of the tissue. The calcium
      content in the tissue varied from 4.9% to 7.8% of dry weight. Electron
      diffraction demonstrated a pattern consistent with hydroxyapatite. Brightfield
      transmission electron microscopy showed that the crystals were acicular and when
      measured under electron diffraction dark field imaging were 16.6 +/- 3.8 (beta
      GP), 16.4 +/- 3.8 nm (ATP), and 17.0 +/- 6.3 nm (PEA) in length. The crystals
      were similar in size (16.0 +/- 5.5 nm) and appearance to the crystals in the in
      vivo calcified cartilage. This data suggests that the mineralization that occurs
      in vitro is similar to the in vivo cartilage.

PMID- 10207188
TI  - Engineering bone regeneration with bioabsorbable scaffolds with novel
      microarchitecture.
AB  - Critical-sized defects (CSDs) were introduced into rat calvaria to test the
      hypothesis that absorption of surrounding blood, marrow, and fluid from the
      osseous wound into a bioabsorbable polymer matrix with unique microarchitecture
      can induce bone formation via hematoma stabilization. Scaffolds with 90%
      porosity, specific surface areas of approximately 10 m2/g, and median pore sizes
      of 16 and 32 microm, respectively, were fabricated using an emulsion freeze
      drying process. Contact radiography and radiomorphometry revealed the size of the
      initial defects (50 mm2) were reduced to 27 +/- 11 mm2 and 34 +/- 17 mm2 for CSDs
      treated with poly(D,L-lactide-co-glycolide). Histology and histomorphometry
      revealed scaffolds filled with significantly more de novo bone than negative
      controls (p < 0. 007), more osteoid than both the negative and autograft controls
      (p < 0.002), and small masses of mineralized tissue (< 15 mm in diameter)
      observed within the scaffolds. Based on these findings, we propose a change in
      the current paradigm regarding the microarchitecture of scaffolds for in vivo
      bone regeneration to include mechanisms based on hematoma stabilization.

PMID- 10207189
TI  - Design of biomimetic habitats for tissue engineering with P-15, a synthetic
      peptide analogue of collagen.
AB  - In tissues, collagen forms the scaffold for cell attachment and migration, and it
      modulates cell differentiation and morphogenesis by mediating the flux of
      chemical and mechanical stimuli. We are constructing biomimetic environments by
      immobilizing a collagen-derived high-affinity cell-binding peptide P-15 in three
      dimensional (3-D) templates. The cell-binding peptide can be expected to
      transduce mechanical forces. In their physiological environment, periodontal
      ligament fibroblasts (PDLF) are subject to significant mechanical forces. We have
      examined the behavior of human PDLF in culture on particulate bovine anorganic
      bone mineral (ABM) coated with P-15 (ABM-P-15). Greater numbers of cells
      associated with ABM-P-15 compared to ABM alone. Higher levels of incorporation of
      radiolabeled precursors in DNA and protein were consistent with the presence of
      larger numbers of cells on ABM-P-15 compared to ABM cultures. Scanning electron
      microscopic examination showed that cultures on ABM-P-15 generated highly
      oriented 3-D colonies of elongated cells and formed copious amounts of fibrous as
      well as membranous matrix reminiscent of ligamentous structures. PDLF cultured on
      ABM formed sparse monolayers with little order and a meager matrix. Alizarin Red
      stained the matrix of particle associated cells and inter-particle cellular
      bridges in P-15-associated cultures, indicating mineralization. 3-D colony
      formation and ordering of cells along with increased mineralization suggests that
      the coupling of cells to the ABM matrix through P-15 may provide a biomimetic
      environment permissive for cell differentiation and morphogenesis. Our studies
      suggest that ABM-P-15 templates may be effective as endosseous grafts, and, when
      seeded with PDLF, these matrices may serve as tissue engineered substitutes for
      autologous bone grafts.

PMID- 10207190
TI  - Cyclic strain effects on human monocyte interactions with endothelial cells and
      extracellular matrix proteins.
AB  - Human vascular endothelial cells (ECs) are exposed to various levels of
      hemodynamic forces, cyclic strain, and shear stress in vivo. Here, we examined
      the in vitro effects of the various levels (0-6%, 7-16%, and 17-25%) of strain at
      60, 30, and 15 cycles per minute (cpm) on human monocyte adherence to endothelial
      cells and extracellular matrix protein preabsorbed surfaces. Monocyte adhesion to
      endothelial cells under cyclic strain significantly increased. At both 30 and 60
      cpm, ECs under strains of 7-16% and 17-25% showed >52% and >117% higher monocyte
      adhesion than endothelial cells under static condition when monocytes were added
      for 0.5 h. This increase in monocyte adhesion to ECs under cyclic strain remained
      significantly higher even after 24 h of incubation. Human monocyte adhesion to
      extracellular matrix protein preabsorbed surfaces differed depending on the
      specific extracellular matrix protein. Monocytes adhered to collagen type I and
      fibronectin preabsorbed surfaces >50% under 0-6% strain, >23% under 7-16% strain,
      and >52% under 17-25% strain at 15 and 30 cpm compared to the collagen type V
      preabsorbed surface. However, when extracellular protein preabsorbed surfaces
      under cyclic strain were compared to the control static condition, monocyte
      adhesion did not significantly change on most of other surfaces. These results
      suggest that cyclic strain may play a role in the regulation of monocyte
      endothelial cells/extracellular matrix interactions in vivo.

PMID- 10207191
TI  - Clinical evaluation of efficacy and safety of a new method for chemo-mechanical
      removal of caries. A multi-centre study.
AB  - The aim of the study was to evaluate the clinical efficacy and safety of a new
      method (Carisolvtrade mark) for chemo-mechanical removal of caries. At four
      centres, 137 consecutive patients (64 females and 73 males aged 3-85 years, mean
      35) entered a prospective, controlled, randomised open study. One primary caries
      lesion with distinct dentine involvement was selected per patient. A total of 116
      lesions in permanent and 21 in deciduous teeth were selected. Caries was removed
      with traditional drilling or the new method. Gel was applied onto the carious
      dentine and the softened caries gently removed with specially designed hand
      instruments. New gel was applied and the procedure was repeated until no more
      debris could be removed and the surface was hard as judged by clinical criteria
      (probing and visual inspection). An independent examiner judged the cavity being
      caries-free or not, using clinical criteria. One hundred and thirteen patients
      were randomised for gel treatment and 24 for drilling. Three patients selected
      for drilling did not complete the treatment. Total caries removal was achieved in
      106 cases with gel and in 19 with drilling. The reasons for incomplete caries
      removal were step-by-step excavation in 5 cases, unsuccessful caries removal in 1
      case for each treatment, while 2 cases refused inspection. Mean (+/- SD) time for
      caries removal was 10.4 (+/-6.1) min with the gel method and 4.4 (+/-2.2) min
      with drilling. Mean volume of gel used was 0.4 (+/-0.2) ml. Eighty-two of 107
      patients perceived that the new method caused less discomfort compared to
      drilling. Dentine caries was effectively removed using the Carisolv method
      without any adverse reactions.

PMID- 10207192
TI  - A low concentration of carbonic anhydrase isoenzyme VI in whole saliva is
      associated with caries prevalence.
AB  - Carbonic anhydrases maintain pH homeostasis in various tissues of the human body
      by catalyzing the reversible reaction CO2 + H2O <=> HCO3- + H+. Carbonic
      anhydrase isoenzyme VI (CA VI) is secreted into human saliva by the serous acinar
      cells of the parotid and submandibular glands. Although it represents about 3% of
      the total protein in stimulated parotid saliva, its exact physiological
      significance in the saliva has not been established. In the present study, saliva
      samples were collected under strictly controlled conditions from young, healthy
      men and assayed for CA VI concentrations using a specific time-resolved
      immunofluorometric assay. Salivary secretion rate, pH, buffering capacity, alpha
      amylase activity levels, lactobacillus and Streptococcus mutans counts were also
      determined, and the results were correlated with the dental status of the
      subjects. Salivary CA VI concentration, pH and buffering capacity values
      correlated negatively with the numbers of decayed, missing and filled teeth (DMFT
      index). The correlations between salivary CA VI concentration and DMFT index were
      most significant in subjects with poor oral hygiene. No correlation was found
      between salivary CA VI concentration and lactobacillus or Streptococcus mutans
      counts. As predicted, salivary lactobacillus and Streptococcus mutans counts
      showed a close positive correlation with the DMFT index. In contrast, no
      significant correlation was seen between salivary secretion rate or amylase
      activity and the DMFT index. The present results indicate that low salivary CA VI
      concentrations are associated with increased caries prevalence, particularly in
      subjects with neglected oral hygiene.

PMID- 10207193
TI  - Salivary carbonic anhydrase isoenzyme VI is located in the human enamel pellicle.
AB  - Salivary carbonic anhydrase (CA VI) appears to protect teeth from caries via
      mechanisms other than direct regulation of salivary pH and buffering capacity. To
      elucidate whether CA VI acts in the local microenvironment of the tooth surface,
      we studied the location and activity of the enzyme in the human enamel pellicle.
      The study was performed using a specific rabbit antiserum to human CA VI in
      conjunction with immunostaining and immunoblot techniques. CA activity was
      demonstrated using a histochemical staining method. CA VI immunostaining of
      extracted teeth having in vivo formed pellicle showed that the enzyme is present
      in the enamel pellicle. Immunostaining for salivary alpha-amylase, which is known
      to be present in the pellicle, showed a similar staining pattern. The presence of
      CA VI in the enamel pellicle was confirmed by immunoblotting of in vivo formed
      pellicle proteins. In vitro studies showed that CA VI binds to polished enamel
      surfaces from both saliva and solutions of purified enzyme. The intensity of the
      CA VI immunostaining on the enamel surface was dependent on the concentration of
      the applied enzyme. The histochemical staining of in vitro formed enamel pellicle
      confirmed that the bound enzyme retains its enzymatic activity. The presence of
      active CA VI in the human enamel pellicle suggests that it may accelerate the
      removal of acid by functioning locally in the pellicle layer on dental surfaces.

PMID- 10207194
TI  - Associations between microbiological and salivary caries activity tests and
      caries experience in Hungarian adolescents.
AB  - The aim of the study was to assess caries prevalence in connection with salivary
      caries-related findings in 349 14- to 16-year-old Hungarian adolescents living in
      two different cities. DMFT, DMFS means, stimulated salivary flow, buffer
      capacity, mutans streptococci, lactobacilli and candida counts in saliva were
      determined. The ratio of caries-free adolescents was 4.6% in the total population
      sample, DMFT mean values were 7.24+/-4.86, DMFS means 10.50+/-8.35. Mean
      secretion rate of stimulated saliva was 0. 84+/-0.50; a low buffer capacity was
      found in 6.3% of the examined children. The ratio of carriers of mutans
      streptococci, lactobacilli and yeasts in saliva was 89.7, 73.9 and 47.7%,
      respectively. DMFT and DMFS values as well as mutans streptococci and candida
      counts were lower in the capital than in the other city. Statistically
      significant correlations were found between DMFT, DMFS mean values, and salivary
      microbiological counts.

PMID- 10207196
TI  - In vitro remineralization of in vivo and in vitro formed enamel lesions.
AB  - Thin sections of natural white spot enamel lesions (WS) and of artificial in
      vitro lesions (VL) were remineralized simultaneously in vitro. The sections,
      clamped in a PMMA holder, were microradiographed at baseline and after
      remineralization in a calcium- and phosphate-containing solution (pH = 7.0; 1 ppm
      F) after 2 and 4 weeks. All data were analyzed with respect to baseline. The
      results show that the lesion depth values did not change significantly during 2
      and 4 weeks of remineralization. The mineral accumulation (change in DeltaZ),
      however, was substantial and significant in WS and VL. In WS the change in
      mineral accumulation was roughly proportional to the amount of mineral at
      baseline. The WS accumulated more than two times the amount of mineral than VL in
      the same periods of remineralization. After 4 weeks of remineralization the
      maximum mineral value Vmax in the surface layer of the WS was nearly up to the
      sound enamel level thick approximate87 vol%. This study shows that the technique
      and calculation procedure described make this single section method attractive
      for longitudinal demineralization-remineralization studies in vitro or in situ.
      Both WS and VL samples obviously remineralized in vitro similarly with respect to
      the baseline. Furthermore, this in vitro work indicates that remineralization
      inhibitors present in saliva, and previously penetrated into the enamel tissue,
      do not influence remineralization later on.

PMID- 10207195
TI  - Fluoride in enamel lining pits and fissures of the occlusal groove-fossa system
      in human molar teeth.
AB  - The fluoride (F) distribution in enamel lining the occlusal fissures of human
      molars and premolars is difficult to investigate by normal microsampling
      techniques, yet this information is of importance as fissures are particularly
      susceptible to caries. We have used the proton probe to map the distribution of F
      and Ca in sections of 17 molar teeth collected from Danish and New Zealand
      populations. The caries status of the sectioned fissure was determined by
      microradiography or visually after drying. The probe scans were graphed as
      density images, surface plots and topographical plots. Sound enamel bordering
      grooves and fissures showed a high-F surface layer, in 1 sample approximately 60
      microm wide near the fissure bottom but gradually widening to double this width
      near the fissure opening, and up to 200 microm wide in grooves, while underlying
      enamel had a low and almost constant F level. In this respect fissure and groove
      enamel resembled smooth surface enamel. The F concentration fluctuated along the
      surface layer, reaching maximum values ranging from 1,800 to 4,200 ppm in 5 non
      carious fissures. Incipient caries in fissure enamel usually but not always
      resulted in an increase in F in the outer layer, the F maximum values in 5 such
      samples ranging from 1,900 to 7,200 ppm. F maximum values in outer enamel were
      higher in 7 samples showing advanced caries, 2, 700-10,000 ppm. The lesion
      subsurface body usually showed normal F values, as did carious dentine in the
      advanced lesions. The variable characteristics of the outer layer in sound
      fissure enamel are likely to be the result of a developmental process rather than
      environmental influences. The fact that we normally failed to find increased F
      concentrations in subsurface carious fissure enamel or in underlying carious
      dentine suggests that F does not diffuse into the deep part of fissure lesions,
      and probably has minimal effect on slowing the progress of such lesions, a
      suggestion in accord with clinical findings on the F effect on fissure caries.

PMID- 10207197
TI  - The effect of window width on the demineralization of human dentine and enamel.
AB  - When lesion formation in dental enamel or dentine is studied in vitro, a well
      defined area of the material, a 'window', is exposed to the demineralization
      medium. In the present experiments, we report the effect of window width on
      lesion formation in enamel and dentine. Rectangular windows, longest dimension
      always 5 mm and shortest dimension varying from 0.5 to 5 mm, were exposed to
      demineralization media. Lesions in dentine were formed by placing the specimens
      in an acidified unstirred 6% carboxymethyl cellulose (CMC) gel, an unstirred 0.5%
      CMC gel, a mildly stirred 0.5% CMC gel, or in a mildly stirred demineralization
      solution. Lesions in enamel were formed only in an unstirred acidified 6% CMC
      gel. pH in the demineralization media was 5.0 in all experiments. The
      microradiographic technique was used to assess lesion depth and mineral loss
      (vol% x microm) of lesions formed. Lesions formed in the unstirred gels were
      deeper, and there was a larger mineral loss, the narrower the window. There was
      no effect of window size on lesions formed in stirred systems. These effects can
      be explained by the strong dependence of concentration gradient in stirred gels
      just outside the exposed window on the window size. The phenomenon found here in
      vitro may at least partly explain why secondary caries may lead to localized, but
      relatively deep, lesions.

PMID- 10207198
TI  - The validity and repeatability of three light-induced fluorescence systems: An in
      vitro study.
AB  - New optical systems are being developed that aim to determine the extent of
      demineralization in enamel. In our laboratory we have compared three such
      systems: a ring illuminator equipped with a laser, a beam splitter also equipped
      with a laser and an intra-oral camera equipped with a white-light arc lamp. The
      aim of the study was to compare the ability of the different optical systems to
      detect small enamel lesions with microradiographic analysis and to determine the
      repeatability of these systems. Forty human enamel specimens (3mm in diameter)
      were mounted in acrylic and polished. The specimens were kept moist throughout
      the study. Each specimen of the four groups was individually exposed to 14 ml of
      Carbopol demineralizing solution for 24, 48, 72 and 96 h, respectively. The
      mineral loss of the 40 specimens was assessed with blue-violet light- induced
      fluorescence. Each image was captured with a video camera and analysed with
      dedicated software. The measurements were repeated 3 times with complete shut
      down of the system in between the measurements. The same measurements were
      performed with the ring illuminator, the beam splitter and the arc lamp. The
      specimens were then cut into thin sections and analysed with microradiography.
      Similar high correlations between microradiography and the light-based analysis
      systems were found for the beam splitter and the clinical caries camera set-up.
      The repeatability was best for the beam splitter set-up. This indicates that the
      light-induced fluorescence measurement technique can be used in different
      configurations and that the repeatability of the measurements is influenced by
      the physical stability of the set-up.

PMID- 10207199
TI  - Detection of early interproximal caries in vitro using laser fluorescence, dye
      enhanced laser fluorescence and direct visual examination.
AB  - This in vitro study evaluated the use of laser fluorescence (LF) for the
      detection of early interproximal carious lesions and whether the detection could
      be enhanced using a fluorescent dye (DELF). Direct visual examination (DV) was
      used for comparison. Eighty extracted teeth were used, arranged in 20 blocks,
      each block having 2 premolars and 2 molars, lined up in a simulated sextant
      situation. After cleaning with a microabrasion kit, a subcontact window on half
      of the surfaces (60) was exposed to Carbopol white-spot solution for 5 days. The
      teeth were remounted in stone and examined by three independent examiners. For LF
      and DELF an argon laser was used (mixed wavelength of 488 and 514 nm) viewed
      through glasses (excluding wavelength <520 nm). For DELF a sodium fluorescein dye
      (0. 075%) was applied before examination. A clinical examination light was used
      for DV. The approximal surfaces were scored for lesion presence or absence. To
      verify lesion presence, the subcontact area was cut perpendicularly to the
      surface, stained with rhodamine B, and images were taken using a confocal
      microscope. The images were analyzed using a histogram program for lesion depth
      and image area. Lesions were present in 62 out of 120 approximal surfaces, with
      an average depth of 60 microm (range 17-190 microm). Sensitivity ranges for LF,
      DELF and DV were 56-74, 61-79 and 58-74%, and specificity ranges 67-78, 86-98 and
      83-97%, respectively. With this model DELF compared favorably with DV and LF in
      sensitivity, but specificity was better for DELF and DV than for LF.

PMID- 10207200
TI  - Digital radiography of interproximal caries: effect of different filters.
AB  - The aim of this study was to compare the effect of different image processing
      modes (filters) on reproducibility and validity of the assessment of
      interproximal carious lesions on digitized radiographic images. Standardized
      radiographs of 34 extracted teeth exhibiting interproximal caries were obtained.
      All radiographs were digitized and using the FRIACOM-software the central depth
      (CD) of each carious lesion was measured on the unchanged radiographic image and
      after use of five different filters with 7fold and 18fold magnification. All
      measurements were repeated after 1 week to estimate reproducibility. Histometric
      CD assessments provided a gold standard for comparison with the radiographic
      measurements (validity). Neither reproducibility nor validity of CD measurements
      were improved by one of the filters. Measurements of dentinal lesions showed a
      statistically higher variability than those of enamel lesions (p<0.001). 18fold
      magnification provided more valid CD measurements than 7fold magnification
      (p<0.001). In this study digital manipulations of radiographic images failed to
      result in statistically significantly improved reproducibility or validity of CD
      measurements.

PMID- 10207201
TI  - Posteruptive changes of electrical resistance values in fissure enamel of
      premolars.
AB  - In studies about 15-25% of the caries-free teeth proved to have as low electrical
      resistance values as carious teeth, due probably to incomplete enamel maturation.
      It was the aim of the present prospective clinical study to investigate, if an
      increase in electrical resistance values could be observed after the eruption of
      premolars. The electrical resistance measurements were performed in children who
      were patients of the Dental School of the University of Marburg, Germany. The
      first measurement was made when a premolar was erupting or when it had erupted
      within 12 months before. The electrical resistance measurements were repeated
      every 3-6 months until the 24th posteruptive month. The measuring device
      consisted of an AC ohmmeter modified by Gente indicating the real component of
      the impedance and employing a frequency of 500 Hz and an amplitude of about 1
      microA. For erupting teeth a mean resistance value of 17+/-15 kohm was computed
      when the contact fluid had been NaCl (A). The corresponding values were 72+/-51
      kohm when distilled water (B) had been applied and 392+/-374 kohm when the
      initially saliva-coated teeth had briefly been dried (C). The mean resistance
      values of the premolars increased continuously from the eruption up to the 15th
      posteruptive month. This observation was independent of the three modes of
      measuring that had been used. It is concluded that enamel maturation leads to an
      increase in electrical resistance. To improve accuracy of caries diagnosis with
      electrical resistance measurements, the posteruptive age of teeth should be taken
      into account. In addition, electrical resistance measurements offer the
      opportunity to observe enamel maturation in vivo noninvasively.

PMID- 10207202
TI  - The relationship between habitual clove cigarette smoking and a specific pattern
      of dental decay in male bus drivers in Jakarta, Indonesia.
AB  - This study has been conducted to establish the relationship between habitual
      smoking of clove cigarettes and a specific type of dental decay. A retrospective
      cohort study of 1,160 bus drivers in Jakarta who smoked clove cigarettes and non
      smokers showed that a specific type of decay occurs in terms of form, location
      and pathology. The prevalence was 55.8%. The type of decay is affected by the
      number of years of smoking and the number of cigarettes smoked each day. Thirty
      two percent of the lesions were on the buccal surfaces of the upper teeth, 39.3%
      on the buccal surfaces of the lower teeth, and 18% of palatal surfaces were
      affected. The prevalence of clove cigarette caries was related to years of
      smoking and numbers of cigarettes smoked per day. Of the men who smoked 10 years
      or less, 27% had caries. The prevalence increased to 79.6% for those smoking for
      11-15 years. For those smoking for more than 15 years the prevalence was 89.3%.
      The relative risk of those smoking 7-12 cigarettes a day was 2.66 (p<0.0001)
      compared to those smoking 0-6 cigarettes a day. The relative risk increased to
      3.19 in those smoking 13-18 cigarettes and 2.96 (p<0.0001) in men smoking more
      than 18 cigarettes per day.

PMID- 10207203
TI  - Potential usefulness of basic fibroblast growth factor as a treatment for stroke.
AB  - Within the past few years, a growing body of evidence has accumulated indicating
      that exogenously administered neurotrophic growth factors may limit the extent of
      acute ischemic neural injury and enhance functional neurorecovery following
      stroke. One of the most widely studied growth factor in this regard is basic
      fibroblast growth factor (bFGF). In preclinical studies, bFGF administered
      intravenously within hours after the onset of ischemia reduces infarct size,
      presumably due to direct protection of cells at the borders (penumbra) of
      cerebral infarction. On the other hand, if bFGF is administered intracisternally
      starting at one day after ischemia, infarct size is not reduced, but recovery of
      sensorimotor function of the impaired limbs is increased, presumably due to
      enhancement of new neuronal sprouting and synapse formation in the intact
      uninjured brain. Clinical trials of the intravenous administration of bFGF as a
      cytoprotective agent in acute stroke are in progress. Trials of the delayed
      administration of bFGF as a recovery-promoting agent in subacute stroke are
      anticipated.

PMID- 10207204
TI  - Effects of subcortical cerebrovascular lesions on cortical hemodynamic parameters
      assessed by perfusion magnetic resonance imaging.
AB  - A simultaneous decrease of cerebral blood volume (CBV) and cerebral blood flow
      (CBF) has been described after subcortical stroke with positron emission
      tomography. However, this imaging modality cannot be applied routinely to stroke
      patients. Dynamic susceptibility contrast-enhanced MRI techniques (DSC-MRI) might
      be interesting in the assessment of these effects. Dynamic T2-weighted echo
      planar imaging was used to produce DSC-MR images during an intravenous bolus
      injection of gadopentetate dimeglumine in 9 patients who experienced a
      subcortical stroke involving thalamus or basal ganglia and in 8 control subjects.
      A series of 50 consecutive images at 1-second intervals was acquired at the
      anatomic level of the centrum semiovale quite distant from the subcortical
      lesion, rCBF and rCBV were determined over frontal and parietal regions of
      interest and through the entire cortical mantle. DSC-MRI enabled the detection of
      hemodynamic changes induced by subcortical stroke. Analysis of rCBV and rCBF
      values showed that the hemodynamic parameters were significantly decreased on the
      affected side. In controls mean rCBF and rCBV values recorded over the whole
      cortical mantle of each hemisphere showed no significant interhemispheric
      asymmetry.

PMID- 10207205
TI  - Cerebrovascular reactivity evaluated by transcranial Doppler: reproducibility of
      different methods.
AB  - Transcranial Doppler is routinely used to assess the cerebrovascular reactivity,
      despite scarce information on its reproducibility. We evaluated the
      reproducibility of cerebrovascular reactivity measurements by this method
      utilizing different vasodilatory and vasoconstrictor stimuli. The cerebrovascular
      reactivity was measured in 45 healthy volunteers during hypercapnia induced by
      inhalation of a mixture of 5% CO2 and 95% O2, breath holding and rebreathing, and
      during hypocapnia induced by voluntary hyperventilation. Three sets of
      measurements were performed at times 0, 1, and 24 h to assess the within-observer
      short- and long-term reproducibility. The reproducibility was analyzed using the
      intraclass correlation coefficient. For the CO2 inhalation method, a good short
      term (rI = 0.55; 95% CI = 0.39-0.68) and a good long-term (rI = 0.43; 95% CI =
      0.25-0.59) reproducibility was found. For the breath-holding method a good short
      term agreement was found (rI = 0.41; 95% CI = 0.22-0. 57), while the long-term
      reproducibility was poor (rI = 0.17; 95% CI = -0.03-0.36). Rebreathing showed a
      fair (rI = 0.31; 95% CI = 0.11-0. 48) short-term and a poor (rI = 0.17; 95% CI = 
      0.03-0.36) long-term reproducibility. For voluntary hyperventilation, the short
      term reproducibility was good (rI = 0.53; 95% CI = 0.36-0.66), and the long- term
      reproducibility was fair (rI = 0.31; 95% CI = 0.11-0.48). In our study, CO2
      inhalation and voluntary hyperventilation had the highest reproducibility and
      should be preferred when assessing cerebral vasoreactivity, especially in follow
      up studies.

PMID- 10207206
TI  - Cerebrovascular response to dynamic changes in pCO2.
AB  - Fifty-six subjects with carotid artery disease were assessed by measuring the
      cerebral blood flow velocity (CBFV) change in response to inhalation of 5% CO2 in
      air whilst continuously monitoring the blood pressure (BP). Coherent averaging of
      the data characterised differences in CBFV, BP, resistance area product and
      critical closing pressure during changes in end-tidal CO2 (ETCO2). The results
      primarily demonstrate that the augmentation of ETCO2 increases the CBFV and BP,
      causing a pressure autoregulatory response, and allows the processes of pressure
      autoregulation and cerebral vascular reserve to be differentiated.

PMID- 10207207
TI  - Prospective study on the complication rate of carotid surgery.
AB  - BACKGROUND: Randomized trials of carotid endarterectomy for high-grade stenosis
      have shown a benefit for surgery under the condition of low perioperative
      complication rates. Concerns have been expressed that the complication rates of
      carotid surgery are higher in everyday practice and may vary considerably between
      centers. We prospectively established the complication rate for carotid surgery
      in a single institution. DESIGN: Prospective 2-year study. All patients received
      pre- and postoperative neurological evaluation. Laboratory tests included pre-
      and postoperative brain imaging, intracranial and neck vessel sonography,
      conventional angiography, magnetic resonance angiography, and intraoperative
      monitoring. PARTICIPANTS: 108 consecutive patients: 54 symptomatic patients
      fulfilling the inclusion criteria of the European Carotid Surgery Trial (ECST)
      and 54 asymptomatic patients fulfilling the inclusion criteria of the North
      American Trial on Asymptomatic Stenoses (ACAS). SETTING: Single academic center
      with a high volume of carotid endarterectomies (>50 per year). Participating
      center in ECST. MAIN OUTCOME MEASURES: Stroke or death as defined in the
      randomized trials. RESULTS: The overall complication rate was 8.3% (95% CI 4.1
      15.6%). Complications were more frequent in patients with symptomatic stenosis
      (11.1%, CI 4.6-23.3%) than in asymptomatic cases (5.6%, CI 1.5-16.4%). Three
      patients died (2 strokes, 1 myocardial infarction). Disabling strokes were found
      in 2 patients (Rankin scale scores 3 and 4). Nondisabling strokes (Rankin scale
      score 1 and 2) occurred in 4 patients. The complication rates for symptomatic and
      asymptomatic patients were higher than the ones reported in the randomized
      trials, but 95% confidence intervals showed that the differences were not
      statistically significant. The point estimates of complication rates still
      supported a benefit of surgery for patients with symptomatic stenosis, but denied
      a positive effect of endarterectomy for patients with asymptomatic stenosis.
      CONCLUSION: In this center, a beneficial effect of carotid surgery for
      asymptomatic stenoses cannot be safely assumed.

PMID- 10207208
TI  - Vocal cord paresis in acute ischemic stroke.
AB  - We prospectively determined the frequency of vocal cord paresis (VCP) among first
      ever acute ischemic stroke patients. Vocal cords were examined endoscopically
      within 48 h of stroke onset, at 1 week and 1 month. Of the 54 study patients,
      64.8% had lacunar (group 1), 22.2% cortical/large subcortical (group 2), 9.3%
      lateral medulla (group 3) and 3.7% other brainstem (group 4) infarcts. VCP was
      found in 11 (20.4%): 11.4% of group 1, 16.4% of group 2, 100% of group 3 and 0%
      of group 4. VCP was contralateral to the brain lesion in groups 1 and 2, and
      ipsilateral in 80% of group 3. VCP was strongly correlated with dysphonia (p <
      0.0001) and resolved in 2/11 patients after 1 week and in 5/11 after 1 month. Our
      finding of VCP among acute ischemic stroke patients questions the belief that the
      nucleus ambiguous is invariably bilaterally innervated by supranuclear centers.

PMID- 10207209
TI  - Three years after in-patient stroke rehabilitation: A follow-up study.
AB  - A 3-year follow-up study was performed aimed at describing the outcome for
      severely affected stroke survivors who had undergone geriatric in-patient
      rehabilitation. Living conditions, psychological well-being, and changes in
      functions were assessed in 55 survivors. Twenty-five people were living in the
      community, 15 in apartment hotels or homes for the aged and 15 in nursing homes.
      From discharge to follow-up 11 people had had to move to an accommodation
      offering more support. Living alone, recurrent strokes and functional decline
      were associated with moving. Many of those living in the community were supported
      by relatives or home help services. Home adjustments and assistive devices were
      common and in most cases were aimed at facilitating transfers and bathroom
      activities. Motor function had deteriorated from discharge to follow-up,
      otherwise no statistically significant changes were seen in the survivors'
      abilities and functions. Most survivors had in fact been able to maintain their
      functions or to make further improvements. Also, their psychological well-being
      seemed quite good. These results should encourage rehabilitation efforts for
      elderly people severely affected by stroke.

PMID- 10207210
TI  - Positional vertebrobasilar transient ischaemic attacks treated with vertebral
      angioplasty.
AB  - We report the case of a man presenting with a brain-stem stroke from which he
      recovered fully, who developed right-sided weakness and numbness on walking
      despite no demonstrable postural fall in arterial blood pressure. Angiography
      revealed an occluded left vertebral artery, a tight stenosis at the origin of the
      right vertebral artery and non-patent left posterior communicating artery.
      Percutaneous transluminal angioplasty to the right vertebral stenosis results in
      a good angiographic result, and remission of symptoms which has persisted for 1
      year. Identification of such patients with vertebrobasilar positional
      haemodynamic symptoms due to a focal stenosis is important as angioplasty offers
      an effective therapeutic option.

PMID- 10207211
TI  - Stroke treatment guided by transcranial Doppler monitoring in a patient
      unresponsive to standard regimens.
AB  - Today secondary prevention of stroke is based on large clinical trials with the
      disadvantage of a lack of individual pathophysiological aspects. This is mainly
      due to the difficulty in identifying the source of stroke reliably and rapidly in
      these patients. Recurrent microembolic events detected by transcranial Doppler
      monitoring (TCM) has been suggested to individualize treatment. We describe a
      patient with recurrent ischemic events in the posterior circulation. Repeated TCM
      of the PCA disclosed microembolic events in the course of an acute embolic lesion
      pattern demonstrated by MRI. Detection of high-intensity transient signals by TCM
      provided a useful guidance of pathophysiologically oriented treatment in this
      patient.

PMID- 10207212
TI  - Painful oculomotor nerve palsy - A presenting sign of internal carotid artery
      stenosis.
AB  - We report a 72-year-old patient presenting acute painful partial left IIIrd nerve
      palsy with pupillary involvement. Due to the patient's age and mild
      hyperlipidemia a microangiopathic ischemic origin was assumed after a compressive
      or inflammatory cause had been excluded by magnetic resonance imaging, blood and
      cerebrospinal fluid analyses. Carotid ultrasound examination disclosed a high
      grade stenosis of the ipsilateral internal carotid artery (ICA). In the absence
      of diabetes mellitus, other significant vascular risk factors and
      leukoencephalopathy indicative of advanced arteriosclerotic disease, we suggest a
      pathogenetic role of the ICA stenosis in ischemic IIIrd nerve palsy. The
      frequency of a IIIrd nerve palsy as the presenting symptom in patients with ICA
      stenosis as well as the frequency of an ICA stenosis being the cause in patients
      with isolated IIIrd nerve palsy is not well documented in the literature. Both
      seem to be rare but may be underestimated. We advocate cervicocerebral ultrasound
      examination in patients presenting IIIrd nerve palsy with no obvious or a
      presumed ischemic cause.

PMID- 10207213
TI  - Subarachnoid hemorrhage due to septic embolic infarction in infective
      endocarditis.
AB  - During antibiotic therapy, a 56-year-old man with a Streptococcus bovis
      endocarditis developed an infarction of the right middle cerebral artery (MCA).
      Thirty hours after stroke onset, cranial computed tomography controls
      demonstrated a secondary subarachnoid hemorrhage, marked in the cistern of the
      right MCA. The latent period, cerebrospinal fluid analysis, angiographic and
      pathologic findings favor the assumption of a pyogenic arterial wall necrosis of
      the MCA due to a septic embolus. This pathomechanism of intracranial hemorrhage
      in infective endocarditis should be distinguished from a rupture of a mycotic
      aneurysm.

PMID- 10207214
TI  - Isolated anterior cerebral artery infarcts: A series of 16 patients.

PMID- 10207215
TI  - Cerebral embolism and Doppler ultrasound.

PMID- 10207217
TI  - Changes in gastrointestinal permeability in celiac disease.
AB  - Increased gastrointestinal permeability was found in celiac disease already 20
      years ago. Originally a genetical defect was supposed leading to elevated
      permeability and later to celiac disease. However, patients under long-term
      gluten-free diet normalized their permeability tests. On the other side,
      unaffected relatives of patients with celiac disease showed high permeability but
      not different from patients with irritable bowel syndrome and with a tendency for
      normalization during follow-up. In active symptomatic celiac disease,
      permeability is elevated in the gastroduodenum - measured by sucrose test - as
      well as in the small intestine - measured by lactulose/mannitol ratio. The
      sensitivity in active celiac disease is high (near 100%), the specificity is low
      due to high permeability in many intestinal diseases as in acute infectious
      gastroenteritis, Crohn's disease, nonsteroidal anti-inflammatory drug treatment,
      etc. In contrast, lactulose/mannitol test permeability is much less sensitive in
      silent celiac disease without diarrhea (74%). The real importance of permeability
      disease is established by its use for follow-up of celiac patients under gluten
      free diet whereas it is correlated to the degree of mucosal atrophy. In vitro
      tests also show increased lactulose mucosal to serosal flux in celiac disease,
      but not correlated to oral permeability test. In conclusion, lactulose/mannitol
      test is the only noninvasive functional test in celiac disease which has
      essential importance in active celiac disease and in follow-up under diet.

PMID- 10207216
TI  - Antibodies in relation to gluten intake.
AB  - Serum reticulin, endomysial and gliadin antibody tests are used in serological
      screening and case finding of coeliac disease, as well as the novel tissue
      transglutaminase antibody test. None of these tests are 100% predictive, however.
      Reticulin/endomysial antibodies predict forthcoming coeliac disease in
      individuals with normal small-bowel mucosal morphology. The effect of a gluten
      free diet can be monitored with serological tests. A positive test result often
      indicates an inadequate gluten-free diet. However, slight dietary transgressions
      and minor mucosal damages cannot always be revealed with the serological tests.
      Therefore, small-bowel mucosal biopsy remains the most sensitive method to
      monitor the effect of a gluten-free diet.

PMID- 10207218
TI  - In vivo gluten ingestion in coeliac disease.
AB  - Studies to determine the nature of the cereal component toxic to patients with
      coeliac disease have concentrated on wheat due to its nutritional importance. A
      number of in vitro studies have indicated the presence of one or more coeliac
      disease-activating epitopes with the N terminus of the A gliadin molecule. In
      vivo challenge with three synthetic peptides subsequently indicated the toxicity
      of a peptide corresponding to amino acid 31-49 of A gliadin. Changes induced by
      this peptide included a decrease in the ratio of villous height to crypt depth, a
      decrease in enterocyte surface cell height and an increase in intra-epithelial
      lymphocyte count. There was evidence of mRNA for the pro-inflammatory cytokincs
      interferon gamma and interleukin 2 within 2 h of the in vivo challenge. We
      examined electron-microscopically biopsies from patients with coeliac disease
      challenged with gluten to determine the subcellular sites where gliadin co
      localised with T-cell receptor subunits and HLA antigens. There were differences
      in co-localisation patterns between treated and untreated coeliac patients. These
      differences and the different patterns of gliadin staining within enterocytes of
      coeliac patients and controls, observed by others, suggest that gliadin may be
      metabolised via a different immunogenic pathway in coeliac disease. This might
      result in an abnormal presentation to the immune system, triggering a pathogenic,
      rather than a tolerogenic response.

PMID- 10207219
TI  - In vitro model of the pathogenesis of celiac disease.
AB  - The in vitro challenge of duodenal mucosa with gliadin is a useful model to
      reproduce the immunological features of celiac disease (CD) and allows the study
      of early pathogenetic events in this disease. With this model it was shown that
      antigens such as ICAM-1 and HLA-DR are upregulated as early as 1-2 h after
      gliadin challenge in patients with CD. After 24 h the lamina propria contained
      CD4+ T cells expressing the IL-2 receptor alpha-chain, which is a sign of
      activation. Intraepithelial lymphocytes increased in number and showed
      proliferative activity. After in vitro stimulation with gliadin, endomysial
      antibodies were found in the supernatant of the cultured mucosa from patients
      with CD following a gluten-free diet. This supported the notion that endomysial
      antibodies are at least in part produced locally. The model was also successfully
      used to identify toxic constituents of gliadin. Presently, organ culture is not
      commonly used for diagnostic purposes.

PMID- 10207221
TI  - Genetic epidemiology in inflammatory bowel disease.
AB  - Family studies of different designs have been carried out in the last few years.
      Five to ten percent of patients have another case of inflammatory bowel disease
      (IBD) among their first-degree relatives, with about 75-80% concordance for the
      same disease within the family. About 20% of multi-affected families present both
      cases with ulcerative colitis and Crohn's disease. The population relative risk
      in first-degree relatives of patients show a 14-15 times higher prevalence of
      IBD. Prevalence values of 1.5-3.5% in first-degree relatives have been found,
      with an even higher calculated lifetime risk especially in offspring and siblings
      of patients with IBD. Earlier disease onset in offspring of patients with IBD
      have consistently been found, and genetic anticipation has been hypothesized. The
      phenomenon, however, may be a result of a combination of a time trend -
      increasing the incidence of Crohn's disease - and the fact that patients with
      early onset of IBD may have lower fertility and therefore may be underrepresented
      in the parent-child pairs studied. Twin studies have shown significantly higher
      concordance rates in monozygotic than in dizygotic twins. Further, the
      concordance rate in monozygotic twins is higher in Crohn's disease than in
      ulcerative colitis, indicating a stronger genetic influence in this condition.
      Disease course and prognosis within families have been studied without convincing
      concordance found in this respect among family members.

PMID- 10207220
TI  - Genetics of the immune response to gluten in coeliac disease.
AB  - Accumulating evidence indicates that coeliac disease (CD) is a multifactorial
      disorder where several heritable factors in conjunction with environmental
      factors are involved in the disease development. Gluten proteins are a critical
      environmental factor as the presence of disease in affected individuals is
      strictly dependent on dietary gluten exposure. Most likely coeliac patients have
      genetically shaped immune responses to gluten proteins that cause intestinal
      pathology. Many of the CD genes thus supposedly encode variants of proteins with
      immune functions. HLA has been identified as a major genetic factor, but yet no
      further genes have been identified. There probably exist several predisposing non
      HLA genes, but available data indicate that the heritable contribution by each of
      them can be small. Combined genetic and functional studies will hopefully
      identify additional predisposing genes in the future.

PMID- 10207222
TI  - Genetics of inflammatory bowel disease. The candidate gene approach:
      susceptibility versus disease heterogeneity.
AB  - Ulcerative colitis and Crohn's disease are complex diseases of unknown etiology.
      Several genes are involved in the susceptibility. These genes are necessary to
      suffer from these diseases but not sufficient. Environmental factors trigger the
      inflammatory response. Evidence is accumulating that this response is abnormal in
      these patients. Therefore, the study of genes that are involved in the regulation
      of the inflammation may help to clarify the pathogenesis of the disease. The
      working hypothesis is that HLA and cytokine gene polymorphisms, of extreme
      importance in the regulation of inflammation, contribute to determining the
      heterogeneity of the disease and the prognosis. In this case, the candidate genes
      are those involved in the regulation of the immune response of the host. These
      studies may be of great importance in the tailoring of an appropriate treatment
      for particular subgroups of patients. A premise for the success of these studies
      is to use a solid classification, which should take into account the dynamic
      process and the natural evolution of the disease; to use a carefully selected and
      ethnically matched group of healthy controls, and to use the advanced molecular
      biological typing techniques. In the present article, this concept is explored by
      taking into account some of the recent findings obtained with the HLA and
      cytokine gene polymorphisms in inflammatory bowel diseases. The results support
      the concept that these gene polymorphisms are of greater importance in
      determining the severity of the disease than in determining the susceptibility to
      suffer from the disease. From this point of view, these studies are complementary
      and a necessary addition to studies using the whole genome approach in the effort
      to understand the genetics of these chronic multifactorial diseases.

PMID- 10207223
TI  - Genome-wide scanning in inflammatory bowel diseases.
AB  - Inflammatory bowel diseases (IBD) are multifactorial traits involving both
      environmental and genetic factors. In order to identify the IBD susceptibility
      genes, two groups of strategies have been developed. In the candidate gene
      approach, a specific hypothesis is tested by usually investigating the prevalence
      of specific alleles in groups of affected and control individuals with no
      familial relationship. Such association studies are powerful and straightforward.
      However, they are limited by possible recruitment biases and a multitesting
      problem due to the large number of possible candidate genes. Furthermore, they
      rely on the existence of a founder effect. In the genome scanning searches, no
      prior assumption is made on the susceptibility genes. The studies are based on
      cosegregation (or linkage) analyses performed on families with several affected
      members. Their drawbacks are the lack of statistical power and the low resolution
      of the localization. Nonetheless, using genome-wide screens, two IBD loci have
      been localized by several independent groups on chromosomes 12 and 16. Additional
      IBD loci have been proposed by individual groups on chromosomes 1, 3, 4, 7, 11,
      15 and X. In order to gain wide acceptance, the latter localizations are to be
      confirmed by additional independent studies. Identification of IBD susceptibility
      genes would represent a key step in the understanding of the pathogenic mechanism
      of these diseases. However, in complex disorders, genes are only a part of the
      risk factors. Epidemiological studies looking for environmental factors are thus
      complementary of the genetic approach.

PMID- 10207224
TI  - Genetics of inflammatory bowel disease. A personal view on progress and
      prospects.
AB  - Clinical, epidemiological and molecular data reported in the last 5 years have
      provided strong evidence that genetic factors are important in susceptibility to
      both Crohn's disease and ulcerative colitis. The model of disease inheritance
      which best fits the epidemiological data is that Crohn's disease and ulcerative
      colitis are related polygenic diseases. However, genetic heterogeneity is likely
      to be extensive, and may well underlie the variability in clinical presentation
      associated with inflammatory bowel disease. Considerable progress has already
      been made in identifying potential disease susceptibility loci using the
      technique of genome-wide scanning. There is optimism that international
      collaborative studies will allow fine mapping of the loci implicated on
      chromosomes 16 and 12. The identification of novel susceptibility genes has
      become a realistic goal for investigators. Once this has been achieved, there are
      likely to be immediate clinical benefits, both in understanding disease
      pathophysiology, and in disease management.

PMID- 10207225
TI  - Somatostatin and octreotide: physiological background and pharmacological
      application.

PMID- 10207226
TI  - The role of octreotide in the treatment of gastroenteropancreatic endocrine
      tumors.
AB  - Gastrointestinal-endocrine pancreatic (GEP) tumors are rare, occurring in less
      than 1% of the population. They are usually divided into functionally active or
      nonfunctioning tumors. Functionally active tumors produce a variety of substances
      (mainly peptides or serotonin). The tumors are classified according to the
      dominant clinical syndrome that they cause. Surgery is the treatment of choice in
      patients with GEP tumors and it should always be considered, even if total tumor
      excision cannot be achieved. Reduction in tumor mass (debulking) may improve the
      patients symptoms. Medical treatment is used in patients with advanced malignant
      endocrine tumors. The most important compounds to control symptoms in these
      patients are somatostatin analogues. Natural somatostatin is produced in
      different molecular forms and has inhibitory effects on a number of functions.
      The observation of potent inhibitory effects on various hormone-secreting cells
      led to the use of somatostatin for symptomatic treatment of peptide-secreting
      tumors. Natural somatostatin is not suitable for long-term clinical application;
      therefore, synthetic somatostatin analogues were developed with improved
      pharmacokinetic characteristics. The best characterized analogue, octreotide, has
      been successfully applied to patients with functioning GEP tumors. Octreotide can
      dramatically ameliorate the debilitating symptoms of patients suffering from the
      clinical manifestations of endocrine tumors such as diarrhea and flushing. The
      success of octreotide therapy is best reflected in terms of its impact on the
      patient's quality of life as defined by the activity to perform normal daily
      activities.

PMID- 10207227
TI  - The role of octreotide in the prevention of complications following pancreatic
      resection.
AB  - Postoperative complications following major pancreatic surgery are mainly due to
      the difficulties of performing a safe and proper anastomosis between the stomach
      or small bowel and the pancreas. Continuous pancreatic juice secretion and the
      often soft structure of the pancreatic parenchyma are major risk factors. The
      present paper summarizes the results of six previously published, placebo
      controlled, double-blind trials and one open randomized trial analyzing the
      efficacy of octreotide in preventing postoperative complications in patients who
      undergo major pancreatic surgery. Patients were given either octreotide (3x100
      150 microg subcutaneously/day) or a placebo perioperatively for 5-7 days starting
      at least 1 h before operation. The patients were monitored postoperatively for
      typical postoperative complications such as: leakage of the anastomosis,
      pancreatic fistula, abscess, fluid collection, shock, sepsis, pulmonary
      insufficiency, renal insufficiency, bleeding, postoperative pancreatitis, and
      death. Six of the seven studies showed significantly fewer postoperative
      complications in the octreotide group in comparison with the placebo group
      (p<0.05). The effectiveness of octreotide was most apparent in the prevention of
      secretion-related complications such as fistula, fluid collection and leakage of
      the anastomosis. These studies demonstrated that inhibition of perioperative
      pancreatic secretion is a viable treatment concept in patients undergoing major
      pancreatic surgery. The perioperative and prophylactic application of octreotide
      in patients who undergo major pancreatic resection reduces the postoperative
      complication rate significantly.

PMID- 10207228
TI  - The role of octreotide and somatostatin in acute and chronic pancreatitis.
AB  - Acute pancreatitis may follow a mild or a severe course. Whereas mild or
      edematous pancreatitis is a self-limiting disease with a low complication rate
      and low death rate, morbidity and mortality in severe or necrotizing pancreatitis
      are still unacceptably high. The major problem is the lack of a specific drug,
      especially in the early phase of the disease, to interfere with the systemic
      inflammatory response syndrome and to limit or prevent complications of the
      disease. Although the initiating pathophysiological process is not known, the
      destruction of the gland ('autodigestion') by digestive enzymes may be
      responsible for disease progression. Inhibition of pancreatic activity, which
      reduces exocrine secretion and further prevents the release and activation of
      enzymes, was therefore suggested as a specific treatment concept. The results of
      clinical investigations using somatostatin or its analogue are controversial,
      since all these trials had low statistical power. In a recent multicenter
      randomized controlled study with a large number of patients (n = 302) (and an
      adequate level of disease severity), no benefit of octreotide on progression or
      outcome was found. Chronic pancreatitis is characterized by an irreversible
      destruction of the exocrine and endocrine pancreatic parenchyma leading to
      maldigestion and diabetes. Pain, which may be caused by increased ductal
      pressure, is one of the most dominant symptoms in chronic pancreatitis. However,
      no beneficial effects on pain with pancreatic exocrine secretion-inhibiting drugs
      have been demonstrated. Treatment of other complications of the disease
      (pseudocyst formation, fistula and pancreatic ascites), with somatostatin or
      octreotide has given conflicting results. However, in a prophylactic clinical
      setting (e.g. elective pancreatic surgery) the inhibition of exocrine pancreatic
      secretion reduces complications.

PMID- 10207230
TI  - Octreotide in the treatment of refractory diarrhea.
AB  - Refractory chronic diarrhea that does not respond to specific antimicrobial
      therapy or standard unspecific medication may present a challenging and serious
      clinical problem. Octreotide is a candidate drug for the treatment of these
      patients as it inhibits gastrointestinal motility, pancreatic secretion and
      inhibits intestinal absorption. Only few mostly uncontrolled studies in small
      patient groups were published evaluating the efficacy of octreotide in the
      treatment of patients with chemotherapy-induced diarrhea, short-bowel syndrome,
      AIDS-associated diarrhea and other conditions with chronic diarrhea not
      responding to standard treatment. Most of these studies are not conclusive as
      they yielded either negative or controversial results. Octreotide may be tried in
      the treatment of refractory diarrhea, in particular AIDS-associated diarrhea if
      patients do not respond to conventional treatment strategies. Well-designed
      controlled trials in large patient groups are needed in order to define the place
      of octreotide in the treatment of patients with refractory diarrhea.

PMID- 10207229
TI  - Somatostatin or octreotide in acute variceal bleeding.
AB  - In patients with cirrhosis, somatostatin or octreotide administration is followed
      by a transient decrease in the hepatic venous pressure gradient and azygos blood
      flow. Although no clear-cut changes in variceal pressure are observed and the
      exact mechanisms of acute hemodynamic changes induced by somatostatin or its
      derivatives are still unknown, this provided the rationale for its use in
      patients with variceal hemorrhage. The only known sustained hemodynamic effect of
      octreotide is to prevent increases in hepatic venous gradient or azygos blood
      flow in response to food intake. Somatostatin infusion can be as effective as
      sclerotherapy in the initial control of bleeding esophageal varices in patients
      with cirrhosis and is associated with fewer complications. Octreotide also seems
      to be as effective as endoscopic therapy in the control of acute variceal
      bleeding, although larger studies should be performed before its efficacy and
      safety profile can be fully evaluated. The combination of somatostatin or long
      acting analogues to endoscopic therapy has recently been delineated as one of the
      most promising approaches in these patients. Early somatostatin administration
      with repeat boluses, starting several hours before sclerotherapy is combined,
      eases the endoscopic procedure and reduces bleeding control failure rate.
      Although two studies also showed that octreotide, when started at the time of
      sclerotherapy or variceal banding, also improves bleeding control, a conclusion
      on octreotide use in these patients is premature. Optimal administration
      schedules and doses of somatostatin or octreotide are still unknown. The safety
      of octreotide in patients with variceal bleeding, which has recently been
      challenged, should be assessed in larger trials. Recent data suggesting that
      octreotide combination to beta-blockers or sclerotherapy may represent a useful
      approach for long-term prevention of rebleeding in these patients will have to be
      confirmed.

PMID- 10207231
TI  - Treatment of acute nonvariceal upper gastrointestinal hemorrhage.
AB  - Hospitalization for nonvariceal upper gastrointestinal hemorrhage (UGIH) is still
      common with an incidence of 100/100,000 adults/year. Mortality rates range
      between 8 and 14%. The most common etiologies of acute UGIH are gastric and
      duodenal ulcers which are associated with older age, Helicobacter pylori
      gastritis and nonsteroidal anti-inflammatory drugs. Approximately 70% of UGIH
      stop spontaneously, 10% bleed continuously and about 20% rebleed in the first 24
      72 h. Mortality and the probability of rebleeding have been related to the
      ulcers' stigmata (Forrest) and to a variety of clinical findings (hematemesis,
      low initial hemoglobin, signs of shock, coagulopathy and liver disease). It is
      well established that only patients with continued bleeding or with a risk of
      rebleeding benefit from endoscopic or medical treatment. Endoscopic treatment
      (including heater probe, bipolar electrocoagulation, laser and injection therapy)
      control active bleeding in up to 90% and reduce significantly the rates of
      further bleeding, the need for blood transfusions, hospital costs and emergency
      surgery. Medical treatment is still controversial although positive results for
      somatostatin and octreotide have been found. A meta-analysis including 1,829
      patients from 14 randomized trials showed the relative risk for continued
      bleeding or rebleeding of 0.53 (95% CI, 0.43-0.63) in favor of somatostatin and
      octreotide. Interventional endoscopy is the first line of treatment for UGIH.
      Somatostatin and its analogue octreotide may be a useful adjunct to endoscopic
      management or alternative when endoscopy is unsuccessful, contraindicated or
      unavailable.

PMID- 10207232
TI  - Role of octreotide and somatostatin in the treatment of intestinal fistulae.
AB  - Intestinal fistulae usually arise as a complication of abdominal surgery. Its
      treatment is complex and intestinal fistula-related morbidity and mortality is
      high. Fistula closure rates under conservative medical treatment vary between 24
      and 72%. Octreotide and somatostatin reduce gastrointestinal, biliary and
      pancreatic secretion and increase intestinal water and electrolyte absorption. In
      recent years, octreotide and somatostatin have been associated with conservative
      medical treatment for patients with intestinal fistulae. Four placebo-controlled
      studies have been published within the past 6 years. The interpretation of their
      results is difficult because patient collectives were small and heterogeneous. In
      one study, somatostatin decreased fistula-related complications when compared to
      placebo, and in another study, octreotide decreased the healing time of
      intestinal fistulae and the time patients required total parenteral nutrition
      when compared to placebo. In contrast, the fistula closure rate, hospitalization
      time and mortality were not influenced by the use of octreotide or somatostatin
      in conservative medical treatment. In conclusion, octreotide and somatostatin
      actually cannot be recommended in the treatment of intestinal fistulae in
      settings outside of controlled trials.

PMID- 10207233
TI  - Platelet-activating factor and platelet-activating factor antagonists in acute
      pancreatitis.
AB  - INTRODUCTION: Acute pancreatitis causes platelet-activating factor (PAF) to be
      released which induces systemic effects that contribute to circulatory
      disturbances and multiple organ failure. PAF has also been implicated as a key
      mediator in the progression of severe acute pancreatitis, which can lead to
      complications and unacceptably high mortality rates. MODE OF ACTION OF PAF IN
      ACUTE PANCREATITIS: Synthesis of PAF is sensitive to biologically active
      mediators seen in many inflammatory processes. PAF significantly potentiates
      pancreatic tissue damage; it causes serum amylase and lipase levels to rise
      significantly, causes scattered haemorrhages and may serve as a primary mediator
      of inflammation. PAF ANTAGONISTS: Several classes of compounds show significant
      PAF antagonisms, and all have shown significant local and systemic effects to
      reduce inflammatory changes. Only lexipafant, however, has been studied in human
      acute pancreatitis. Lexipafant specifically binds to the PAF receptor and is more
      potent than other PAF antagonists. In clinical trials lexipafant reduces organ
      failure and suppresses some aspects of the inflammatory response. CONCLUSION: Our
      understanding of the pathology of systemic complications, and of a central role
      of PAF in mediating an inappropriate inflammatory response has improved in recent
      years. Confirmation of clinical findings with lexipafant will indicate an
      effective new therapy for the treatment of severe acute pancreatitis.

PMID- 10207234
TI  - The bile duct anastomosis in liver transplantation.
AB  - In spite of the dramatic improvement of survival after orthotopic liver
      transplantation over the last decades, biliary tract complications are still the
      'achilles heal' of liver transplantation with a potential risk of significant
      morbidity and mortality. Biliary leaks or strictures, the major types of biliary
      complications, may occur after direct choledocho-choledochostomy (CC) or Roux-Y
      choledocho-jejunostomy (CRY). The majority of these biliary complications,
      however, are often a consequence of surgical technique and therefore potentially
      amenable to improved surgical technique.

PMID- 10207235
TI  - Adjustable silicone gastric banding: can We continue the original technique of
      Kuzmak?
AB  - BACKGROUND: Kuzmak developed a horizontal gastroplasty for morbid obesity using
      his adjustable silicone gastric banding (ASGB). The aim of this study was to
      evaluate the efficiency at weight loss, early and late morbidity and mortality.
      METHOD: The records of 44 patients (mean age 36 years) were reviewed. The
      indication for ASGB was a BMI >40 (group A = 37 patients) or a BMI between 35 and
      40 with obesity-related morbidity (group B = 7 patients). The mean preoperative
      BMI was 44 (+/-5). The paired t test was used to evaluate the BMI. RESULTS: Early
      complications occurred in 5 patients: splenic injury (n = 1), aspiration
      pneumonia (n = 1), wound infection (n = 1), gastric perforation (n = 2);
      mortality was 2%. Late complications occurred in 19 patients: 17 patients (39%)
      had a functional stenosis with pouch dilatation (FSPD) and 6 patients had an
      injection port leakage (14%). At the 1-year follow-up, the mean BMI (of the 39
      patients available) was 30 (+/-5) and remained stable. At 36 months, 54% of group
      A and 100% of group B had a BMI <30. CONCLUSION: The original technique of Kuzmak
      is effective to lose weight. However the technique must be adjusted in order to
      decrease the unacceptable high incidence of FSPD.

PMID- 10207236
TI  - Long-term effects on the regulation of pancreatic secretion after gastric
      surgery.
AB  - BACKGROUND: Apart from smoking, known risk factors for the development of
      pancreatic carcinoma are few, gastric resection being proposed as one. The
      trophic effect of cholecystokinin (CCK) on the pancreatic gland is well known
      from animal experience and increased concentrations of CCK in plasma have been
      shown to induce pancreatic neoplasia experimentally. In several studies the
      release of CCK in response to food ingestion has been shown to be increased
      following gastric surgery. However, in those studies, the time between surgery
      and investigation of the CCK response was short, and methods of CCK analysis have
      since improved. PATIENTS AND METHODS: In patients, partially gastrectomized 8
      years (median) earlier, we studied the plasma concentrations of CCK, insulin and
      gastrin, as well as some specific pancreatic enzymes. The findings were compared
      to an age-matched control group of individuals not subjected to gastric surgery.
      RESULTS: Basal CCK concentrations in the operated group were found to be lower,
      but increased postprandially to the same level as in controls. Serum levels of
      specific pancreatic enzymes were equal in the 2 groups. CONCLUSION: It is
      possible that a disturbed regulation of pancreatic secretion, or a secretory
      dysfunction within the gland, following partial gastrectomy, could contribute to
      the development of pancreatic carcinoma. However, our findings do not favor the
      idea of plasma CCK as a promotor of pancreatic carcinoma.

PMID- 10207237
TI  - Changes in gastric intramucosal pH following mesenteric traction in patients
      undergoing pancreas surgery.
AB  - BACKGROUND/AIM: During major abdominal surgery, mesenteric traction (MT) may
      result in hemodynamic instability mainly due to endogenous prostacyclin release.
      Gastric intramucosal pH (pHi) and PiCO2 are indicators of splanchnic tissue
      perfusion with a predictive value for the postoperative outcome. We investigated
      the influence of MT on gastric pHi and on postoperative outcome in patients
      undergoing pancreas surgery. METHODS: Forty-six consecutive patients scheduled
      for pancreas surgery were investigated. We registered hemodynamics and pHi by
      gastric tonometry and documented postoperative outcome (complications, hospital
      stay). Baseline data (T0) were recorded after skin incision. Further assessments
      followed 30, 60 and 120 min after intentional MT (T1-3) and at the end of surgery
      (T4). RESULTS: Thirty-three patients demonstrated a decrease in mean arterial
      pressure (MAP) following MT, whereas 13 patients showed entirely stable
      hemodynamics. The significant reduction in MAP in patients with an MT response
      was not associated with changes in pHi as compared to patients with no response
      (stable MAP) (T0 7.34 +/- 0.08 vs. 7.35 +/- 0.06; T1 7.34 +/- 0.05 vs. 7.32 +/-
      0.07; T2 7.32 +/- 0. 05 vs. 7.31 +/- 0.08; T3 7.32 +/- 0.05 vs. 7.32 +/- 0.07; T4
      7.26 +/- 0.1 vs. 7.27 +/- 0.08; mean +/- SD, MT response vs. no response).
      Neither MT response nor gastric intramucosal acidosis as evidenced by a pHi <7.32
      at the end of surgery predicted postoperative complications or longer hospital
      stay. CONCLUSION: No deterioration of gastric pHi was found, which could reflect
      acceptable splanchnic perfusion and oxygenation despite systemic blood pressure
      reactions in patients experiencing an MT response.

PMID- 10207238
TI  - Specific prognostic factors for secondary pancreatic infection in severe acute
      pancreatitis.
AB  - BACKGROUND/AIMS: The aim of the present study was to investigate whether there
      are specific prognostic factors to predict the development of secondary
      pancreatic infection (SPI) in severe acute pancreatitis in order to perform a
      computed tomography-fine needle aspiration with bacteriological sampling at the
      right moment and confirm the diagnosis. METHODS: Twenty-five clinical and
      laboratory parameters were determined sequentially in 150 patients with severe
      acute pancreatitis (SAP) and univariate, and multivariate regression analyses
      were done looking for correlation with the development of SPI. RESULTS: Only
      APACHE II score and C-reactive protein levels were related to the development of
      SPI in the multivariate analysis. A regression equation was designed using these
      two parameters, and empiric cut-off points defined the subgroup of patients at
      high risk of developing secondary pancreatic infection. CONCLUSION: The results
      showed that it is possible to predict SPI during SAP allowing bacteriological
      confirmation and early treatment of this severe condition.

PMID- 10207239
TI  - Distal pancreatectomy in chronic pancreatitis.
AB  - BACKGROUND: The indications for a resective procedure in chronic pancreatitis are
      severe pain and local complications. The aim of this study, based on
      prospectively assessed data, was to evaluate distal pancreatectomy in patients
      suffering from chronic pancreatitis localized in the corpus and cauda of the
      pancreatic gland. METHODS: Seventy-four patients undergoing distal pancreatectomy
      were evaluated pre- and postoperatively (after a median observation period of 58
      months) for pain, professional status, alcohol consumption, and endocrine
      function as measured by the glucose tolerance test preoperatively. RESULTS: The
      indication for operation was severe therapy-resistant pain in nearly all patients
      and an inflammatory tumor or pancreatic pseudocysts in over 50% of the patients.
      One fourth of the patients were operated in order to exclude malignancy. Ninety
      five percent of the patients underwent distal pancreatectomy, only in 4 cases
      (5%) was a subtotal (Child) resective procedure performed. In 34% of patients
      undergoing distal pancreatectomy a splenectomy could be avoided. The early
      postoperative complications were few and mostly due to the severe comorbidity of
      the patients. During the median observation period of 58 months 14.7% of the
      patients died due to diseases not related to distal pancreatectomy. Six percent
      of the patients could not be reevaluated and were lost to follow-up. In the
      remaining 59 patients 88% had significantly less pain and 66% had an increase in
      median body weight of 8 kg. Fifty percent of the patients had full or partial
      professional rehabilitation, one fourth was unemployed and 24% had retired due to
      age. 51.7% had a normal endocrine function as assessed by the glucose tolerance
      test, 16.2 and 21.6% had a latent or manifest diabetes mellitus, respectively. In
      74.5% of all patients the endocrine function did not worsen during the
      observation period. CONCLUSION: In comparison to conservative treatment distal
      pancreatectomy is a suitable therapeutic measure in patients with severe pain and
      local complications. It significantly improves the quality of life of patients
      without compromising endocrine function. Postoperative lethality is lower than in
      conservatively treated patients and is not related to distal pancreatectomy.

PMID- 10207240
TI  - Primary choledochorrhaphy after common bile duct exploration.
AB  - AIM: To prove further the safety of primary closure of the common bile duct.
      METHOD: Twenty patients among 99 common bile duct explorations underwent primary
      closure. Pre- and postoperative liver function test, ultrasound and
      intraoperative cholangiography data, operation time, postoperative complications
      and the length of postoperative stay were recorded. RESULTS: Nineteen patients
      did not suffer any biliary complication. One had bile leakage and bile
      peritonitis, and another had duodenal leakage. One case was complicated by
      gastric ulcer perforation. The mean postoperative hospital stay except for the 2
      patients with complications was 8.72 +/- 0.75 days. Preoperative abnormal liver
      function tests recovered within 2-3 weeks after the operation. Postoperative
      ultrasound scan of the biliary tract within 2 months revealed no stenosis and
      residual stone. CONCLUSION: Primary common bile duct closure is a safe
      alternative to routine biliary drainage in selected patients.

PMID- 10207241
TI  - Effect of a microwave coagulator on implanted liver neoplasms in rats.
AB  - An experimental study was conducted to determine the applicability of a microwave
      (MW) source for coagulation and dissection of metastatic tumour and liver
      parenchyma. Twenty PVG rats were studied after implantation of MC28 tumour cells
      into the liver. Eleven days later they underwent sham laparotomy (control) MW
      coagulation of the tumour deposit, local resection of the tumour deposit with 2
      mm clearance or resection of the tumour with MW coagulation of the resection
      zone. The control animals all died with blood-stained ascites and heavy tumour
      burden in the liver. After MW coagulation, tumours disappeared in all but one
      rat. Local resection also led to tumour clearance in 4 of 5 rats. MW coagulation
      of the resection zone allowed rapid bloodless resection, and no tumour recurrence
      was observed after 40-89 days. We conclude that MW coagulation is a potentially
      useful tool for ablation of hepatic metastasis and as an adjunct to hepatic
      resection.

PMID- 10207242
TI  - Multimodal treatment of neuroendocrine tumors of the pancreas and the ampulla of
      Vater.
AB  - Neuroendocrine tumors are not seen frequently. They are most commonly located in
      the small bowel including the vermiform appendix. Neuroendocrine tumors of
      pancreatic origin are extremely rare. Symptoms caused by excessive hormone
      production by large liver metastases often lead to their diagnosis. Preoperative
      diagnostics include analysis of specific hormones in serum and urine, ultrasound,
      CT and somatostatin receptor scintigraphy. Liver metastases of neuroendocrine
      tumors of the pancreas are common at the time of diagnosis. Curative resection
      should be performed whenever possible, although patients often benefit from
      debulking procedures, too. Liver metastases can be subjected to surgical
      resection, embolization, regional chemotherapy or local procedures such as
      alcohol injection or cryoablation. As an exception, liver transplantation can be
      considered in selected cases where radical surgery for the primary tumor could be
      performed and extrahepatic metastases are not present. Supplementary or
      alternative options include octreotide and/or interferon-alpha administration. In
      this article, we report on 6 patients suffering from primary neuroendocrine
      tumors of the pancreas or the ampulla of Vater who were treated at our department
      over the past 5 years. In addition, we discuss our own experience with this rare
      condition in the light of the recent literature.

PMID- 10207243
TI  - Highly aggressive behavior and poor prognosis of small-cell carcinoma in the
      alimentary tract: flow-cytometric analysis and immunohistochemical staining for
      the p53 protein and proliferating cell nuclear antigen.
AB  - The purpose of this study was to determine the clinical course, and effects of
      the histopathologic characteristics of specific tumors, including DNA contents
      and immunohistochemical aspects, in patients with small-cell carcinoma of the
      alimentary tract. Medical records of 14 patients who presented with small-cell
      carcinoma of the alimentary tract were retrospectively reviewed. Primary tumors
      were studied by immunohistochemical and flow cytometric analyses. Of these 14
      small-cell carcinomas, 4 were esophageal, 8 gastric, and 2 colonic tumors. DNA
      aneuploidy was observed in 8 tumors. Staining for the p53 product was positive in
      57.1% of all the tumors. The average proliferating cell nuclear antigen (PCNA)
      labeling rate (LR) was 72.4 +/- 11.6%. The average PCNA LR was significantly
      higher for the p53-positive group (p < 0.05). The estimated median survival was
      253 days for all patients. Noncurative resection was associated with a
      significantly less favorable prognosis (p < 0.01). Distant metastases were
      observed in 13 of 14 patients. A higher PCNA LR of small-cell carcinoma may be an
      unfavorable characteristic of biological behavior. The patients with disseminated
      disease should undergo a symptomatically palliative operation combined with
      chemotherapy.

PMID- 10207244
TI  - Parietal mesh abscess as an original presentation of cancer of the caecum.
AB  - We report a case of cancer of the caecum in a 71-year-old male who presented with
      parietal mesh abscess. Two years before, he was treated for a right inguinal
      hernia by insertion of a Dacron mesh. CT scan then colonoscopy determined the
      existence of a voluminous caecal tumor perforated in the abdominal wall with an
      important abscess around the mesh. Right colectomy and parietal muscles excision
      were performed completed with postoperative radiochemotherapy. At 2 years, there
      is no evidence of recurrence. Atypical features with a hernia mesh repair
      associated with a sudden change in the patient's condition should alert the
      clinician to the possibility of a further subjacent pathological process.

PMID- 10207245
TI  - Juvenile polyposis: case report and assessment of the neoplastic risk in 271
      patients reported in the literature.
AB  - A case of juvenile polyposis is reported and 271 cases are collected from the
      literature. The risk for neoplasia is analyzed and the endoscopic or surgical
      therapy is discussed. The authors conclude that juvenile polyposis should be
      considered as a challenge to the surgeon with regard to familial adenomatous
      syndromes, and strongly recommend a close follow-up of patients with juvenile
      polyposis.

PMID- 10207246
TI  - Differential expression of alphav integrins in K1735 melanoma cells.
AB  - Tumor cell adherence to and migration on the extracellular matrix is an important
      aspect of cancer progression. This interaction with the extracellular matrix is
      mediated primarily through the integrin class of cell adhesion molecules. We
      identified a restricted expression of alphavbeta3 in highly metastatic K1735M2
      and of alphavbeta5 in poorly metastatic K1735C23 murine melanoma cells. The
      highly metastatic cells were ten times more motile on vitronectin and fibronectin
      and approximately three times more invasive through a reconstituted basement
      membrane than the poorly metastatic cells. This motility was inhibited by
      addition of anti-beta3 antibodies. Injection of the alphavbeta3-negative K1735C23
      cells into syngeneic mice resulted in the generation of a metastatic variant
      (K1735C23PM) that neo expressed the alphavbeta3 complex, indicating that
      expression of alphavbeta3 is required for K1735 melanoma metastasis. Injection of
      highly metastatic K1735M2 cells in the presence of blocking antibody to beta3
      reduced tumor size by approximately 80%. Treatment of the K1735M2 cells with a
      retroviral antisense beta3 construct significantly reduced their expression of
      alphavbeta3 and also reduced their motility on extracellular matrix ligands and
      their invasion through a reconstituted basement membrane. In contrast, when the
      K1735C23 cells were treated with a construct containing the full-length beta3
      cDNA, their motility on extracellular matrix proteins and invasion of a
      reconstituted basement membrane were significantly increased. These results
      indicate that alphavbeta3 is required for migration and invasion of K1735
      melanoma cells in vitro and primary tumor growth and metastasis in vivo.

PMID- 10207247
TI  - Metastatic dissemination of human ovarian epithelial carcinoma is promoted by
      alpha2beta1-integrin-mediated interaction with type I collagen.
AB  - Metastatic dissemination of epithelial ovarian carcinoma is thought to be
      mediated via tumor cell exfoliation into the peritoneal cavity, followed by
      adhesion to and invasion through the mesothelium which overlies the contents of
      the peritoneal cavity. In this study, we have utilized short-term primary
      cultures to analyze the effect of specific extracellular matrix proteins on
      properties of human ovarian epithelial carcinoma cells which contribute to the
      invasive phenotype. Analysis of cell:matrix adhesive profiles indicated that
      ovarian carcinoma cells adhere preferentially to type I collagen.
      Immunoprecipitation analyses demonstrated the presence of the collagen-binding
      alpha2beta1 integrin in biotin-labeled ovarian carcinoma cell membranes, and
      cellular adhesion was inhibited by blocking antibodies directed against the
      alpha2 and beta1 integrin subunits. The alpha2beta1-binding peptide Asp-Gly-Glu
      Ala (DGEA) was also moderately effective at blocking adhesion to collagen
      relative to the control peptide Ala-Gly-Glu-Ala (AGEA). Analysis of cell motility
      on protein-coated colloidal gold coverslips demonstrated that ovarian carcinoma
      cells migrate preferentially on type I collagen coated surfaces. Type I collagen
      promoted migration in a concentration-dependent, saturable manner, with maximal
      migration observed at a collagen-coating concentration of 50 microg/ml. Migration
      on collagen was inhibited by antibodies directed against the alpha2 and beta1
      integrin subunits and by DGEA peptide, providing evidence for the role of the
      alpha2beta1 integrin in ovarian carcinoma cell motility. Culturing ovarian
      carcinoma cells on type I collagen gels led to a significant increase in
      conversion of the matrix metalloproteinase 2 zymogen to the 66-kD form,
      suggesting that adhesion to collagen also influences matrix-degrading
      proteinases. These data suggest that alpha2beta1-integrin-mediated interaction of
      ovarian carcinoma cells with type I collagen, a protein prevalent both in the
      mesothelial extracellular matrix and in the peritoneal cavity of ovarian
      carcinoma patients, may function on multiple levels to promote metastatic
      dissemination of ovarian carcinoma cells.

PMID- 10207248
TI  - Elaboration of matrix metalloproteinase inhibitors by human skin in organ culture
      and by skin cells in monolayer culture: relationship to invasion.
AB  - Functional and immunochemical approaches were used to assess matrix
      metalloproteinase (MMP) inhibitors, e.g., tissue inhibitor of metalloproteinases
      1 and 2 (TIMP-1 and TIMP-2), in organ cultures of normal human skin maintained
      under growth factor free conditions or in medium supplemented with a combination
      of growth factors including epidermal growth factor, insulin, and pituitary
      extract. It has previously been shown that under growth factor free conditions,
      normal skin structure and function are maintained for several days, while in the
      presence of these exogenous growth factors, the epithelial cells invade the
      stroma [Invasion and Metastasis 1993;13:225-233]. TIMP-1 was detected in
      equivalent amounts in organ culture fluids under both conditions. TIMP-2 was not
      detected under either condition. Normal epidermal keratinocytes, normal dermal
      fibroblasts, and three different epithelial tumor cell lines were also examined
      for MMP inhibitor expression. Keratinocytes and fibroblasts produced high levels
      of both TIMP-1 and TIMP-2, but in neither cell type was there a significant
      difference between growth factor free and growth factor containing conditions. In
      contrast, the three epithelial tumor cell lines produced low to undetectable
      levels of both TIMP-1 and TIMP-2. These data suggest that acquisition of local
      invasive capacity is not dependent on a reduction in MMP inhibitor expression. A
      reduction in MMP inhibitors may accompany the transition from invasive to
      metastatic tumors.

PMID- 10207249
TI  - Truncated dipeptidyl peptidase IV is a potent anti-adhesion and anti-metastasis
      peptide for rat breast cancer cells.
AB  - A novel adhesion receptor/ligand pair was shown recently to mediate lung vascular
      arrest and metastasis of rat breast cancer cells. The interacting adhesion
      molecules are endothelial dipeptidyl peptidase IV (DPP IV) and tumor cell surface
      associated, polymeric fibronectin (FN). A truncated DPP IV (DPP IV(31-767): amino
      acids 31-767) in which the FN-binding site is preserved is shown here to mask the
      breast cancer cell surface-associated FN complexes, causing a dose-dependent
      inhibition of adhesion to endothelial DPP IV and impeding lung colony formation
      by approximately 80%. Since surface accumulation of FN is chiefly occurring
      during dissemination in the blood and since many cancer cell types have surface
      receptors by which they may initiate FN accumulation on their surfaces, the
      present anti-metastatic treatment modality may extend its efficacy farther than
      appreciated by this study.

PMID- 10207250
TI  - Mechanisms of downregulation of transfected E-cadherin cDNA during formation of
      invasive tumors in syngeneic mice.
AB  - Loss of E-cadherin expression has been observed both in experimental tumors and
      in human cancers and is related to invasiveness and poor differentiation. The E
      cadherin-negative mouse mesenchymal tumor cell line MO4 was transfected with
      several plasmids expressing mouse E-cadherin cDNA. These plasmids differed from
      each other by the extent of E-cadherin-specific 3' untranslated region (UTR)
      sequences and by the use of different constitutive promoters. Transfectants were
      isolated that expressed functional E-cadherin in a homogeneous way. In syngeneic
      mice, such MO4-Ecad transfectants invariably produced malignant fibrosarcoma-like
      tumors, which were completely E-cadherin-negative at the protein level. Northern
      blotting revealed that E-cadherin mRNA expression was downregulated in some but
      not all MO4-Ecad tumors. Downregulation was caused by mRNA instability triggered
      by particular 3' UTR sequences. This in vivo downregulation of E-cadherin in
      malignant MO4-Ecad tumors turned out to be reversible and is likely to be
      mediated by host factors to be further identified.

PMID- 10207251
TI  - Pathophysiology of heart failure.
AB  - Heart failure is a leading cause of mortality and morbidity in Western countries.
      Common etiology is mostly represented by ischemic and hypertensive heart disease.
      Clinically, heart failure can be defined as an impaired cardiac performance,
      unable to meet the energy requirements of the periphery. Pathophysiologically,
      the clinical onset of heart failure symptoms already represents an advanced stage
      of disease when compensatory mechanisms triggered by the underlying decrease in
      contractility are no longer capable of maintaining adequate cardiac performance
      during exercise and, subsequently, under resting conditions. Independent of its
      underlying etiology, cardiac failure is always characterized by an impairment in
      the intrinsic contractility of myocytes. As a consequence of reduced
      contractility, a number of central and peripheral compensatory mechanisms take
      place that are capable of effectively counteracting reduced intravascular
      intrinsic performance for a long period of time. Among them, recruitment of
      preload reserve, enhanced neurohormonal stimulation and cardiac hypertrophy are
      the most important. All of them, however, also carry unfavorable effects that
      contribute to further deterioration of cardiac function. In fact, increased end
      diastolic volume determines increased wall stress that further reduces systolic
      performance; sympathetic and angiotensin stimulation increases peripheral
      resistance and contributes to increase volume expansion; hypertrophic myocytes
      demonstrate impaired intrinsic contractility and relaxation, and hypertrophy
      causes a clinically relevant deterioration of ventricular relaxation and
      compliance that substantially participates in increased end-diastolic pressure,
      and, therefore, to limited exercise performance. Diastolic dysfunction usually
      accompanies systolic dysfunction, although in some cases it may represent the
      prevalent mechanism of congestive heart failure in patients in whom systolic
      performance is preserved. Biological causes of reduced contractility in heart
      failure are not completely elucidated. Changes in myosin composition and in
      sarcoplasmic ATPase activity, causing reduced Ca2+ availability during
      contraction, have been reported, although their exact contribution is not clear.
      Recently, impaired endothelial function has also been described in heart failure,
      and new appealing hypotheses have been made regarding the causative role of
      circulating cytokines like tumor necrosis factor in the pathogenesis of heart
      failure.

PMID- 10207252
TI  - Pathogenesis of renal sodium retention in congestive heart failure.
AB  - This article summarizes briefly some factors responsible for edema in chronic
      congestive heart failure. It is now generally thought that so-called 'backward
      failure' is a manifestation of diastolic dysfunction, while systolic 'pump
      failure' is a disease that depends on two key factors: an inadequate cardiac
      output, and renal salt and water retention. The key elements involved in what
      might be termed the 'integrated volume response' are hemodynamic and renal
      factors. The hemodynamic factors include vasoconstriction, tachycardia and a
      reduced venous capacitance. These responses occur within minutes, while salt and
      water retention occurs over days to weeks. The key renal elements modulating
      sodium retention in congestive heart failure include, at a minimum, four
      variables. First, there is a reduction in renal blood flow produced by the almost
      simultaneous operation of alpha- and beta-catecholamines, antidiuretic hormone,
      the endothelins, and angiotensin II. Second, activation of the tubuloglomerular
      feedback system enhances intrarenal angiotensin II release, which augments
      proximal sodium absorption. In addition, beta-catechols also enhance proximal
      sodium absorption. A third key element involved in renal sodium retention is
      activation of apical sodium channels, ENaC, of principal cells in the cortical
      collecting tubule by aldosterone and by vasopressin. Finally, the inner medullary
      collecting duct becomes resistant to the action of atrial natriuretic peptide,
      thus adding a final dimension to the syndrome of sodium retention in
      underfilling.

PMID- 10207253
TI  - Body impedance studies in end-stage heart failure.
AB  - This study adds another category of patients to those amenable to body impedance
      analysis (BIA). BIA measurements were obtained for the first time in 23 male
      patients with end-stage heart failure who were waiting for heart transplantation,
      and the data were compared with those obtained in 69 healthy controls matched for
      age, sex, height and weight. The data indicate that in end-stage heart failure
      there is an increased reactance (p<0.01) and an altered intracellular
      water/extracellular water ratio (p<0.03) due to the increased intracellular water
      (p<0.01) and decreased extracellular water (p<0.01).

PMID- 10207255
TI  - Diuretic resistance.
AB  - Resistance to diuretic action is frequently encountered in the clinical setting.
      This is best managed by systematically optimizing the pharmacodynamic
      pharmacokinetic factors that may be involved. Important pharmacodynamic measures
      include improving the underlying disease state, restriction of salt intake,
      limiting the use of vasodilators which may cause hypotension, lowering protein
      excretion, and eliminating drugs which may modify the response to the diuretic.
      Pharmacokinetic measures include using doses which result in diuretic excretion
      rates which fall on the steep part of the dose-response curve, sustaining
      diuretic excretion in this range by frequent drug administration, or constant
      infusion, using more bioavailable drugs and drugs which have less hepatic
      elimination, and by increasing the diuretic concentration in blood by
      coadministration with albumin. Using diuretic combinations to systematically
      inhibit absorption in the proximal tubule, Henle's loop, distal convoluted
      tubule, and connecting/collecting tubule will usually effect diuresis in all but
      the most refractory of cases.

PMID- 10207254
TI  - Renal reserve is normal in patients with dilative cardiomyopathy waiting for
      heart transplantation.
AB  - Renal reserve was explored by means of an oral protein load (2 g/kg body weight)
      under the form of cooked red meat in a group of 9 patients with end-stage heart
      failure (ESHF), class III of the New York Heart Association receiving loop
      diuretics and angiotensin-converting enzyme (ACE) inhibitors, and in a group of
      18 healthy controls (HC) matched for age, gender, and height under an identical
      dietary regimen providing 40 cal/kg per day, 1 g/kg body weight of protein per
      day, Na 120 mmol/day, and K 50 mmol/day. Baseline glomerular filtration rate
      averaged 109.5+/-9.89 ml/min x 1.73 m2 in HC and 71.9+/-8.8 ml/min x 1.73 m2 in
      ESHF. Renal plasma flow averaged 540+/-27 ml/min x 1.73 m2 in HC and 235+/-47
      ml/min x 1.73 m2 in ESHF. The filtration fraction was significantly higher in
      ESHF (p<0.01). Renal reserve averaged 26.03+/-3.28 ml/min x 1.73 m2 in HC and
      27.2+/-7.12 ml/min x 1.73 m2 (not significant). Renal reserve averaged 123.9+/
      2.9% in HC and 137.3+/-6.68% in ESHF (not significant). The filtration capacity
      was significantly higher in HC (p<0.001). The data point to a normalcy of renal
      reserve in ESHF which may depend on the chronic use of ACE inhibitors.

PMID- 10207256
TI  - Diuretics in renal failure.
AB  - Fluid retention following reduction in the glomerular filtration rate causes
      extracellular fluid volume expansion that reduces tubular reabsorption by
      residual nephrons, thereby maintaining the external sodium balance. The price
      paid for this is salt-dependent hypertension. Thus, loop diuretics are the best
      treatment for uremic hypertension. Diuretics are also used in chronic renal
      failure to treat edema due to nephrotic syndrome and congestive heart failure
      (CHF). In nephrotics, edema is often refractory to diuretics because of low
      plasma protein, depletion of the intravascular compartment, decrease in the
      protein-bound fraction of the diuretic in peritubular blood, and increase in
      tubular fluid. Thus, higher doses are needed. In uremics with CHF the efficacy of
      diuretics may be hampered because of the reduced renal blood flow. The
      association of dopamine (1-1.5 microg/kg body weight/min) may overcome this
      resistance; improvement in cardiac function by dialysis ultrafiltration may also
      help. Diuretic resistance is sometimes observed; it may be overcome by the
      following procedures: in CHF by the use of digitalis and/or angiotensin
      converting enzyme inhibitors; by substitution of an ineffective loop diuretic for
      another one; by using larger doses of diuretic; by intravenous infusion rather
      than bolus therapy, and by a combination of diuretics acting in different
      segments of the tubule: loop diuretic+thiazide+amiloride. Intravenous infusion of
      20% albumin has also been suggested.

PMID- 10207258
TI  - Early dialysis in heart insufficiency of patients with chronic renal failure.
AB  - In patients with severe heart failure life expectancy is short, the quality of
      life is affected, and the service costs are very high. Drug therapies remain
      restricted despite continuous clinical research. Therefore new therapeutic
      approaches have been attempted to improve the signs and symptoms of the disorder.
      In our study we followed patients suffering from class-IV cardiac failure
      concomitant with chronic renal failure. The patients were initially treated by
      means of hemofiltration, and subsequently they underwent a personalized dialysis
      program. The survival rate after 2 years was 62.5%. In 7 of the 8 patients the
      results revealed a drop to a class-III condition. The hospitalization period was
      limited to a few days. Early dialytic therapy represents a reality for such
      patients.

PMID- 10207259
TI  - Heart transplantation in patients with diuretic resistant heart failure.
AB  - Advanced heart failure is becoming an increasing cause of mortality and morbidity
      in a large number of patients. Heart transplantation is the treatment of choice
      for many selected patients in this group. According to the clinical status at the
      time of transplant, patients may have a different outcome related to the early
      survival, while the late results are similar and not affected by the patient's
      initial clinical status. All surviving patients showed recovery of kidney
      function as soon the cardiac output was restored to normal values. High urine
      output was present in a large number of patients in the early postoperative
      period. However, in severely ill patients with cardiac index <2.5 l/min/m2,
      diuretic resistance and mortality were higher.

PMID- 10207257
TI  - Daily hemofiltration in severe heart failure.
AB  - Heart failure of class IV NYHA has a very severe prognosis. Its most frequent
      electrolytic alterations are hyponatremia, hypokalemia, and hypomagnesemia which
      can cause serious arrhythmias and sudden death. The regulation of the
      electrolytic equilibrium by means of pharmacological therapy becomes impossible
      in patients with severe heart failure resistant to strong doses of diuretics in
      the oligo-anuric phase. This study focused on the use of daily hemofiltration in
      a group of patients suffering from cardiac insufficiency of class IV NYHA. The
      results have been evaluated over 1 year.

PMID- 10207260
TI  - Growth hormone and the heart.
AB  - Until a few years ago, growth hormone (GH) and insulin-like growth factor-1 (IGF
      1) were considered essential only to the control of linear growth, glucose
      homeostasis, and for the maintenance of skeletal muscle mass. A large body of
      evidence recently coming from animal and human studies has unequivocally proven
      that the heart is a target organ for the GH/IGF-1 axis. Specifically GH exerts
      both direct and indirect cardiovascular actions. Among the direct effects, the
      ability of GH to trigger cardiac tissue growth plays a pivotal role. Another
      direct effect is to augment cardiac contractility, independent of myocardial
      growth. Direct effects of GH also include the improvement of myocardial
      energetics and mechanical efficiency. Indirect effects of GH on the heart include
      decreased peripheral vascular resistance (PVR), expansion of blood volume,
      increased glomerular filtration rate, enhanced respiratory activity, increased
      skeletal muscle performance, and psychological well-being. Among them, the most
      consistently found is the decrease of PVR. GH may also raise preload through its
      sodium-retaining action and its interference with the hormonal system that
      regulates water and electrolyte metabolism. Particularly important is the effect
      of GH on skeletal muscle mass and performance. Taking into account that heart
      failure is characterized by left ventricular dilation, reduced cardiac
      contractility, and increase of wall stress and peripheral vascular resistance, GH
      may be beneficial for treatment of heart failure. Animal studies and preliminary
      human trials have confirmed the validity of the GH approach to the treatment of
      heart failure. Larger placebo-controlled human studies represent the main focus
      of future investigations.

PMID- 10207261
TI  - Effects of thyroid hormones on heart and kidney functions.
AB  - Thyroid hormones affect the functions of several organs including the heart and
      kidney. Using isolated left papillary muscles we have investigated the action of
      thyroid hormones on the mechanical and electrical properties of the heart. We
      found that pure hypothyroidism causes a depression in contractile and electrical
      parameters, but we noticed that superimposed hypoparathyroidism accounts for the
      marked prolongation in contractile kinetics and action potential duration. At
      kidney level we have shown that thyroid hormones affect proximal tubular sodium
      transport and this effect is only partially mediated by the action of thyroid
      hormones on Na-K-ATPase activity. Using the micropuncture technique, we
      hypothesized that the early effect of thyroid hormone action is on the potassium
      permeability of proximal tubular cell membrane. This latter effect would explain
      the increase in isotonic fluid reabsorption through an increase in the driving
      force for sodium. Finally, hypothyroid patients have a decrease in glomerular
      filtration rate and renal plasma flow that are completely reversed by thyroxine
      administration. On the other hand, hyperthyroid subjects exhibit a significant
      increase in both parameters.

PMID- 10207262
TI  - Hypertensive nephropathy - an increasing clinical problem.
AB  - Arterial hypertension-related renal damage is an increasingly common problem
      recently, because approximately 25% of patients currently treated with dialysis
      were hypertensive before renal replacement therapy was started. Hypertension is
      also known as a metabolic disease, while carbohydrate, purine and lipid
      disturbances are the features of this syndrome. On the other hand, the
      progression of renal disease depends on the extent of tubulointerstitial injury.
      For this reason, we undertook a study to evaluate the relationship between
      excretion of the markers of tubular damage (NAG) and some parameters of
      carbohydrate, purine and lipid metabolism in untreated essential hypertension.
      Both healthy volunteers (n = 15) aged 32. 6+/-7.8 and essential hypertensives (n
      = 25) aged 37.24+/-11.39 underwent the same tests. These tests were performed at
      2-day intervals: intravenous glucose tolerance test with 0.5 g/kg b.w. as 40%
      glucose solution and oral fructose load test with 1.0 g/kg b.w. Area under
      glucose curve (GA) and serum uric acid post-fructose (PUAA) were calculated.
      Fasting: insulin, total cholesterol and LDL, triglycerides, free fatty acids
      (FFA) and urine excretion of NAG, albumin were determined. Glomerular filtration
      rate was estimated as creatinine clearance. Hypertensives showed statistically
      higher BMI (p<0.007), NAG (p<0.02), total cholesterol (p<0.01), LDL (p<0.007),
      FFA (p<0.007), insulin (p<0.01), PGA (p<0.01) and PUAA (p<0.03). NAG excretion
      correlated positively with WHR (r = 0.40), MAP (r = 0.47) and PUAA (r = 0.47) in
      hypertensives only. We presume that tubular injury at an early stage of renal
      damage in patients with essential hypertension could be a part of metabolic
      syndrome X.

PMID- 10207263
TI  - Systolic hypertension: the nephrologist's point of view.
AB  - The elevation of systolic blood pressure associated with aging has been
      considered for years a physiologic phenomenon. This idea was based on the
      repeated observation that, also after middle age, a large majority of individuals
      in industrialized countries experience a continuous and progressive increase over
      time in systolic blood pressure, not in diastolic blood pressure. However, some
      individuals in industrialized countries and most individuals in nonindustrialized
      countries do not acquire an increased systolic blood pressure over time proving
      that the age-associated rise in systolic blood pressure is not an inevitable
      phenomenon. The change in systolic blood pressure over time strongly reflects
      lifestyles. Diet-dependent factors such as body weight, alcohol intake, and
      balance between dietary salt and potassium, are important in favoring the age
      associated increase in systolic blood pressure, independently of several
      confounders. Epidemiologic studies suggest that elevation of systolic blood
      pressure is a risk factor for cardiovascular diseases: it relates to high
      incidence of lethal and nonlethal cardiovascular events also in the presence of
      diastolic blood pressure in the nonhypertensive range. Controlled clinical trials
      show that the treatment of isolated systolic hypertension reduces the number of
      cardiovascular events. In addition to cardiovascular disease, systolic blood
      pressure relates also to microalbuminuria, an index of early glomerular damage,
      to long-term incidence of end-stage renal disease, and, in hemodialyzed patients,
      to premature death. Thus, high systolic blood pressure appears an unhealthy
      condition also for patients with or at risk for kidney diseases.

PMID- 10207264
TI  - Blood pressure in nuns in a secluded order: A 30-year follow-up.
AB  - The powerful effect of psychosocial and acculturating influences on population
      blood pressure trends seems to be confirmed, through longitudinal observations,
      in the nuns in a secluded order. After initial observations had been made on
      culture, body form, blood pressure, diet, and other variables in 144 nuns and 138
      lay women, included as a control group, a 30-year follow-up study was undertaken.
      Most striking were opposite trends noted between the two groups in blood pressure
      trend. During the follow-up period, blood pressure remained remarkably stable
      among the nuns. None showed an increase in diastolic blood pressure over 90 mm
      Hg. By contrast, the control women showed the expected increase in blood pressure
      with age. This resulted in a gradually greater difference (delta>30/15 mm Hg) in
      systolic and diastolic blood pressure between the two groups, which was
      statistically significant. In addition, cardiovascular morbidity and mortality,
      expressed as the outcome of fatal and nonfatal events, were different in the two
      groups. They were significantly more common in the lay women than in the nuns.
      Comparisons between survival curves were statistically significant (p = 0.0043
      for fatal events; p = 0.0056 for nonfatal events) between the two groups. In
      conclusion, it seems reasonable to attribute much of the difference in blood
      pressure and cardiovascular events, to the different burden in psychosocial
      factor and to the preserved peaceful lifestyle of the nuns.

PMID- 10207265
TI  - Management of hypertension in renal disease.
AB  - The treatment of systemic hypertension in chronic renal disease is now mostly
      based on the administration of drugs which are able to reduce proteinuria and to
      slow down the progressive functional deterioration. Angiotensin-converting-enzyme
      inhibitors (ACEI), which lower both proteinuria and blood pressure, have emerged
      as drugs of choice in proteinuric patients with either normal renal function or
      mild to moderate chronic renal failure. In non proteinuric nephropathies no
      controlled studies exist demonstrating the superiority of ACEI over other drugs.
      In these conditions calcium antagonists might also be used. The approach to
      patients with hypertension and renal disease should always take into
      consideration the quality of the results that are to be achieved. If the aim is
      to control blood pressure and to protect other organs at risk, then a variety of
      drugs can be used. If the aim is to reduce proteinuria and slow down progression,
      then ACEI, possibly associated with calcium antagonists, are the drugs of choice.

PMID- 10207266
TI  - Hypertension in dialysis patients.
AB  - Hypertension is a major risk for cardiovascular complications in dialysis
      patients. The pathogenesis of hypertension is multifactorial and is not
      completely understood. Hypervolemia has always been considered a major
      pathogenetic factor. In addition, a disturbed hormone profile with an activated
      renin angiotensin system, increased catecholamine, vasopressin and endothelin,
      and perhaps decreased nitrous oxide activity seem to play a role in the high
      incidence of hypertension in dialysis patients. The influence of autonomic
      dysfunction on blood pressure control in hemodialysis patients is not clear. The
      frequent use of erythropoietin during the last decade may have contributed to the
      increased incidence of hypertension in the dialysis population. Data from the
      First Report on Dialysis and Transplant in Sicily showed that hypertension is the
      cause of end-stage renal disease in 8% of dialysis patients and that the
      incidence of hypertension, as a cause of end-stage renal disease, increased with
      age.

PMID- 10207267
TI  - Left ventricular hypertrophy in daily dialysis.
AB  - Cardiac hypertrophy, a well-known independent risk factor for cardiovascular
      death, is a very frequent complication in ESRD patients. Its frequency tends to
      be even higher in dialyzed patients due to the fact that the current dialytic
      treatments are unable to keep under a satisfactory control the various
      responsible factors and particularly the blood pressure, which is largely the
      most important. Daily hemodialysis, a more frequent schedule consisting of 6-7
      sessions/week lasting 2 or more hours, has definitely proved its superiority in
      controlling blood pressure and in improving anemia, and thus has the requisites
      for positively influencing cardiac hypertrophy. In fact, a series of studies,
      both retrospective and prospective, performed during the last years by our group,
      have confirmed that this new, more frequent and thus more physiological schedule,
      is able not only to stop the progression of the cardiac hypertrophy in uremic
      patients but also to revert toward the normality, in a relatively short time.
      This appears to be essentially a consequence of the excellent blood pressure
      control, which in turn derives from the easier control of the true dry weight,
      achievable with this type of dialytic treatment.

PMID- 10207269
TI  - Cardiovascular mortality and morbidity in dialysis patients.
AB  - Dialysis patients constitute a high-risk group for cardiovascular disease, which
      accounts for 40% of deaths in these patients. After stratification for age, race
      and gender, cardiovascular mortality is several orders of magnitude (10-20 times)
      higher in dialysis patients than in the general population. A clustering of risk
      factors renders dialysis patients especially susceptible to cardiovascular
      disease. Their morbidity and mortality can be favorably altered by interventional
      measures which systematically address and modify each individual risk factor. It
      is necessary to institute intervention during the course of progressive renal
      failure, well before the onset of end-stage renal disease and the initiation of
      dialysis.

PMID- 10207268
TI  - Homocysteine, a new crucial element in the pathogenesis of uremic cardiovascular
      complications.
AB  - Most large observational studies available today establish that moderate
      hyperhomocysteinemia, either genetically or nutritionally determined, is an
      independent risk factor for myocardial infarction, stroke, and thromboembolic
      disease. This is also true for chronic renal failure patients, who exhibit a high
      prevalence of hyperhomocysteinemia (85-100%), which reaches high plasma
      concentrations (20-40 microM, while control values range between 8 and 12
      microM). After a renal transplant, homocysteine levels decrease, but tend to be
      higher than normal. The cause of hyperhomocysteinemia in renal failure is still
      obscure, since recent data have questioned the previous notion that a net
      homocysteine renal extraction and/or excretion take place in man. No matter the
      cause of its increase, the sulfur amino acid homocysteine is thought to induce an
      increment in cardiovascular risk through three basic biochemical mechanisms: (1)
      homocysteine oxidation, with H2O2 generation; (2) hypomethylation through S
      adenosylhomocysteine accumulation, and (3) protein acylation by homocysteine
      thiolactone. The final result is membrane protein damage, endothelial damage, and
      endothelial cell growth inhibition, among other effects. Hyperhomocysteinemia, in
      general, is susceptible of therapeutic intervention with the vitamins involved in
      its metabolism. Depending on the cause, vitamin B6, vitamin B12, betaine, and/or
      folic acid can be effectively utilized. Chronic renal failure patients benefit
      from folic acid in high dosage: 1-2 mg are usually not effective ('relative
      folate resistance'), while 5-15 mg reduce homocysteine levels to a 'normative'
      range (<15 microM) in a substantial group of patients. Good results are also
      obtained in transplant patients, best with a combination of folic and vitamin B6.
      The results of the interventional trials focusing on the possible reduction in
      cardiovascular risk after homocysteine-lowering therapy, both in the general
      population and in end-stage renal disease, are expected soon, as well as the
      genetic and biochemical studies in suitable models, with the aim to clarify the
      cause-effect link suggested by the numerous observational and basic science
      studies.

PMID- 10207270
TI  - The management of hypotension in dialyzed patients.
AB  - Acute hypotension is a frequent hemodialysis complication. This intra-treatment
      vascular instability is a multifactorial process in which procedure-related and
      patient-related factors may influence the decrease in plasma volume and the
      impairment of cardiovascular regulatory mechanisms. Identification of the most
      susceptible patients and of the various risk factors may contribute to
      significantly improving cardiovascular stability during dialysis. In some high
      risk patients, continuous monitoring of the various parameters can predict the
      appearance of symptomatic hypotension and help to prevent its onset.

PMID- 10207271
TI  - Anemia and cardiovascular complications: iron and EPO impact.
AB  - Management of end-stage renal disease (ESRD) has been revolutionized by the
      advent of erythropoietin replacement. We briefly review its characteristics and
      clinical use. Also emphasized is the importance of iron deficiency in limiting
      the clinical response to erythropoietin therapy. Iron-replacement therapy in ESRD
      patients is briefly discussed.

PMID- 10207272
TI  - Diagnosis, pathogenesis, and treatment of dialysis-related amyloidosis.
AB  - Dialysis-related amyloidosis (DRA) is a major complication of chronic renal
      failure and long-term renal replacement therapy. Beta2-Microglobulin is a major
      constituent of amyloid fibrils in DRA. Amyloid deposition mainly involves bone
      and joint structures, presenting as carpal tunnel syndrome, destructive
      arthropathy, and subchondral bone erosions and cysts. While a definitive
      diagnosis of DRA can only be made by histological findings, various imaging
      techniques often support diagnosis. The molecular pathogenesis of this
      complication remains unknown. Recent studies, however, have suggested a
      pathogenic role of a new modification of beta2-microglobulin in amyloid fibrils,
      i.e. the advanced glycation end products (AGEs). Increased carbonyl compounds
      derived from autoxidation of both carbohydrates and lipids modify proteins in
      uremia, leading to augment not only AGE production but also the advanced
      lipoxidation end product production. Thus, uremia might be a state of carbonyl
      overload with potentially damaging proteins ('carbonyl stress'). Therapy of DRA
      is limited to symptomatic approaches and surgical removal of amyloid deposits.
      High-flux biocompatible dialysis membranes could be used to delay DRA
      development.

PMID- 10207273
TI  - Urinary indoxyl sulfate is a clinical factor that affects the progression of
      renal failure.
AB  - We recently demonstrated that indoxyl sulfate is a stimulating factor for the
      progression of chronic renal failure (CRF). In this study we determined whether
      the urine or serum levels of indoxyl sulfate are related to the progression rate
      of CRF in undialyzed uremic patients. Fifty-five CRF patients with a serum
      creatinine of >2 mg/dl who had not been treated with an oral sorbent (AST-120)
      were randomly enrolled in the study. We measured the serum and urine levels of
      indoxyl sulfate, and estimated the recent progression rate of CRF as the slope of
      the reciprocal serum creatinine versus time (1/S-Cr-time) plot. The mean urinary
      amount of indoxyl sulfate in the patients was 60 mg/day. Those with indoxyl
      sulfate urine levels of >60 mg/day had a significantly faster progression rate of
      CRF than those with <60 mg/day. Especially, those patients with indoxyl sulfate
      urine levels of >90 mg/day had the highest CRF progression rate and those with
      indoxyl sulfate urine levels of <30 mg/day had the slowest CRF progression rate.
      Urinary indoxyl sulfate had a significantly negative correlation with the slope
      of the 1/S-Cr-time plot. However, the serum level of indoxyl sulfate or the ratio
      of serum indoxyl sulfate to creatinine was not significantly correlated with the
      slope of the 1/S-Cr-time plot. In conclusion, high urine levels of indoxyl
      sulfate are related with a rapid progression of CRF in undialyzed uremic
      patients. Thus, urinary indoxyl sulfate is one of the clinical factors that
      affect CRF progression.

PMID- 10207274
TI  - Central administration of antiserum to vasoactive intestinal peptide delays and
      reduces luteinizing hormone and prolactin surges in ovariectomized, estrogen
      treated rats.
AB  - The present study investigated the role of hypothalamic VIP in the regulation of
      the LH and PRL surge using immunoneutralization of endogenous VIP in mature
      ovariectomized (OVX), estradiol benzoate (EB)-treated female Wistar rats. We
      compared the effect of intracerebroventricular (i.c.v.) injections of a VIP
      antiserum (VIP-Ab) with that of saline (Ctr) on LH and PRL profiles in two
      separate groups of rats following two subcutaneous EB injections on days 8 and 9
      after OVX. VIP-Ab or Ctr injections were given during the second half of the dark
      period, i.e. at 22:00 h (day 9), and, in addition, the following morning, i.e. at
      08:00 h (day 10), just before the expected onset of the LH surge. Hourly blood
      samples were collected between 09:00 and 18:00 h on day 10. In addition, we
      studied the reproducibility of EB-induced LH and PRL surges and compared the
      effect of Ctr and VIP-Ab treatment on sequential surges in individual OVX
      females, i.e. 10 and 23 days after OVX, using each animal as its own control.
      Although we observeda large variation in the height and timing of LH and PRL peak
      levels between EB-treated females, the characteristics of successive surges of
      individual rats were highly reproducible. This reproducibility suggests that
      differences in functioning of the suprachiasmatic nucleus as well as in the
      response of the hypothalamus to steroid feedback largely explain the normal
      variation in hormone responses between rats. The VIP-Ab treatment resulted in a
      significant delay in the time course and a strong reduction of the magnitude of
      the afternoon LH and PRL surge. When analyzed within individual females, the
      effect of VIP-Ab treatment was even more pronounced due to a reduction in
      variability when each animal was used as its own control. These results suggest
      that hypothalamic VIP is an important regulator of both the timing and the
      magnitude of the EB-induced LH and PRL surge in the OVX rat, and suggest that its
      role may be stimulatory in this respect.

PMID- 10207275
TI  - Photoperiod affects the gonadotropin-releasing hormone neuronal system of male
      prairie voles (Microtus ochrogaster).
AB  - In order to maximize survival, animals inhabiting temperate and boreal latitudes
      exhibit numerous adaptations to changing seasons. Central among this suite of
      coping strategies is the cessation of breeding during the suboptimal conditions
      of winter. Many nontropical rodents inhibit reproduction well in advance of
      winter in response to short day lengths. Male prairie voles (Microtus
      ochrogaster) are small temperate-zone rodents that vary in their reproductive
      response to photoperiod. Some male voles undergo complete gonadal regression
      during short days (responders) while others fail to inhibit reproduction when
      exposed to short day lengths (nonresponders). The neuroendocrine mechanisms
      regulating this differential response to photoperiod have not been investigated
      in this species. Presumably, photoperiod can act at any or all levels of the
      hypothalamo-pituitary-gonadal (HPG) axis to regulate reproduction. The present
      study sought to determine the contribution of the GnRH system to this variable
      reproductive response to photoperiod. Male prairie voles were housed in either
      long or short day lengths for 10 weeks. As shown with immunohistochemistry, voles
      that underwent gonadal regression in response to short photoperiods exhibited
      increased GnRH neuron numbers in the preoptic area/anterior hypothalamus (POA/AH)
      relative to both long-day animals and short-day voles that maintained
      reproductive function. Mean optical density of staining and cell size did not
      differ among groups. These data suggest that the differential reproductive
      response to photoperiod in male voles is mediated, in part, by alterations in the
      GnRH neuronal system.

PMID- 10207277
TI  - Estrogen transiently increases delayed rectifier, voltage-dependent potassium
      currents in ovine gonadotropes.
AB  - Treatment of gonadotropes with estrogen (E) changes the electrophysiological
      response to gonadotropin-releasing hormone (GnRH) such that the cells are
      hyperpolarised immediately after stimulation with GnRH and then generate action
      potentials more frequently than non-E-treated cells. We investigated the role of
      K+ current in this altered response to GnRH using cultures of ewe pituitary cells
      enriched for gonadotropes. K+ current density was measured using nystatin
      perforated whole-cell recordings in the voltage clamp mode. Treatment of cells
      with E for 16-20 h significantly (p < 0.01) increased the unit K+ current to 180%
      of that in vehicle-treated cells. Outward current in these cells flows
      predominantly through voltage-dependent, delayed rectifier K+ channels (IK), and
      E alters the magnitude of this current. The effect of E to increase the K+
      current was dose- and time-dependent and was maximal after 16-20 h. The unit K+
      current values returned to pre-treatment levels after 36 h of E treatment.
      Several cells were studied both before and after E treatment and the average
      effect of E on these cells was to increase the unit K+ current by 90%. The time
      course of the effect of E on K+ current density is the same as the effect of E to
      increase LH release in vitro and in vivo. We conclude that the increase in K+
      current may be an important part of the mechanism whereby E acts on gonadotropes
      to facilitate the LH surge which triggers ovulation.

PMID- 10207276
TI  - A comparative study of the effects of nitric oxide and carbon monoxide on the in
      vivo release of gonadotropin-releasing hormone and neuropeptide Y from rat
      hypothalamus during the estradiol-induced luteinizing hormone surge: estimation
      by push-pull perfusion.
AB  - Recent evidence suggests that nitric oxide (NO), a free radical gas, plays an
      important role in regulating the function of a variety of neuroendocrine systems.
      With respect to the hypothalamo-pituitary-gonadal axis, a stimulatory effect of
      NO on the release of gonadotropin-releasing hormone (GnRH) from rat hypothalamus
      has been demonstrated in vitro. However, no previous study has reported NO
      stimulated secretion of GnRH from in vivo hypothalamus, and also the precise
      cellular site of action of NO within the GnRH neuronal system remains to be
      elucidated. In the present study, utilizing the push-pull perfusion technique of
      rat hypothalamus, we examined the effect of L-arginine (L-Arg), an NO donor, on
      the release of GnRH, neuropeptide Y and cyclic GMP (c-GMP), which is a pivotal
      second messenger molecule of the NO system. For comparison, we also examined the
      effect of carbon monoxide (CO), another putative gaseous neurotransmitter, using
      hematin, a CO donor. During the period of 11.00-18.00 h, we collected blood and
      hypothalamic perfusates from ovariectomized adult rats that had been implanted
      with an estradiol capsule 2 days before. During the entire period of observation,
      L-Arg (1.0 or 10 mM), hematin (10 or 100 microM) or artificial cerebrospinal
      fluid alone (as the control) was infused into the medial preoptic area (MPOA)
      where there are cell bodies of GnRH neurons, or the median eminence-arcuate
      nucleus complex (ME-ARC) where axon terminals of GnRH neurons are localized.
      Although 10 mM of L-Arg significantly stimulated GnRH and c-GMP, but not
      neuropeptide Y, levels in both the MPOA and ME-ARC, GnRH and c-GMP in the ME-ARC
      were already increased by 1.0 mM of L-Arg. By contrast, both concentrations of
      hematin were without effect at either site of the hypothalamus. This study is the
      first to demonstrate that NO is capable of stimulating GnRH release from rat
      hypothalamus in vivo. Our data also suggests that both cell bodies and axon
      terminals of GnRH neurons may be sites of action of NO. Our data do not support a
      previous study by other investigators that reported a stimulatory effect of CO on
      the GnRH release.

PMID- 10207278
TI  - GABA exerts stimulatory and inhibitory influences on gonadotropin II secretion in
      the Atlantic croaker (Micropogonias undulatus).
AB  - Possible involvement of gamma-aminobutyric acid (GABA) in the control of
      gonadotropin II (GTH II) secretion was investigated during different phases of
      the seasonal gonadal cycle of the Atlantic croaker (Micropogonias undulatus).
      Intraperitoneal administration of GABA (100 microgram/g) elicited a significant
      increase in plasma GTH II levels in croaker with regressed or pre-recrudescence
      phase gonads, whereas it did not significantly affect GTH II levels during the
      early- to mid-recrudescence phase of the gonadal cycle in this species. On the
      other hand, GABA induced a dose-related inhibition of GTH II secretion in fish
      with fully recrudesced gonads. Similar opposite changes in GTH II levels were
      observed when croaker with regressed and fully recrudesced gonads were injected
      with the GABA transaminase inhibitor, gamma-vinyl GABA (10 and 100 microgram/g).
      This suggests an involvement of endogenous GABA in the control of GTH II
      secretion. GABA (1-100 microM) did not significantly alter GTH II release from
      pituitary fragments from regressed or fully recrudesced fish incubated in vitro,
      suggesting the lack of a major direct influence at the pituitary level. Muscimol
      (GABAA receptor agonist, 1 microgram/g) treatment mimicked both the stimulatory
      and inhibitory effects of GABA, whereas injection of baclofen (GABAB receptor
      agonist, 1 microgram/g) had no significant effect on basal or a gonadotropin
      releasing hormone (GnRH) analog-induced GTH II secretion. Pretreatment of fish
      with bicuculline (1 microgram/g), a GABAA antagonist, completely blocked the
      stimulatory influence of GABA on GTH II secretion in croaker with regressed
      gonads and partially blocked the inhibitory effect in individuals with fully
      recrudesced gonads. The results demonstrate that GABA exerts opposite influences
      on GTH II secretion at two different stages of the gonadal cycle of croaker, and
      acts primarily via GABAA type receptors. Thus, GABAergic pathways may be
      important in mediating seasonal influences on GTH II secretion in this species.

PMID- 10207279
TI  - Involvement of gamma-aminobutyric acid in the control of GTH-1 and GTH-2
      secretion in male and female rainbow trout.
AB  - The potential role of the neurotransmitter gamma-aminobutyric acid (GABA) in the
      control of the secretion of the two pituitary fish gonadotropins (GTH-1 and GTH
      2) was investigated in male and female rainbow trout (Oncorhynchus mykiss). The
      presence of glutamate decarboxylase-positive fibers in the neurohypophyseal
      digitations adjacent to the gonadotropic cells was demonstrated by means of
      double immunohistochemistry, providing a morphofunctional support for potential
      GABA-gonadotropin interactions in both sexes. In spermiating males, in vivo
      treatment with GABA did not affect basal gonadotropin release, but stimulated GTH
      1 release when coadministered with a gonadotropin-releasing hormone analogue
      (GnRHa), and potentiated GnRHa-stimulated GTH-2 release. In vitro, using
      dispersed pituitary cells, GABA stimulated basal GTH-1 and GTH-2 secretion, in a
      dose-dependent manner, and potentiated salmon GnRH effect on both hormones. In
      mature females, GABA induced in vivo a strong elevation of plasma GTH-2 levels
      after 2- 6 h of injection, but had no effect in vitro. GABA treatment in vivo was
      also stimulatory in recrudescent females, slightly increasing plasma GTH-2 levels
      in both saline- and GnRHa-treated fish (GnRHa alone has no effect at this stage).
      Immature fish were unresponsive to GABA/GnRHa treatments but, after steroid
      implantation [testosterone (T) or estradiol] for 13 days, injection of GABA
      stimulated GTH-2 release in vivo (also GTH-1 slightly in T-implanted fish). In
      conclusion, GABA has an overall stimulatory action on GTH-1 and GTH-2 secretion
      in rainbow trout, which depends on the sex and the reproductive stage of the
      fish. The stimulatory action of GABA might be exerted, at least in part, directly
      onto the gonadotropes, as it stimulates basal and GnRH-induced GTH-1 and GTH-2
      secretion from dispersed pituitary cells.

PMID- 10207280
TI  - Fos expression in the female rat brain during the proestrous prolactin surge and
      following mating.
AB  - A prolactin (PRL) surge occurs in the female rat during proestrus in response to
      elevated estradiol levels. The elevated release of ovarian steroids on the day of
      proestrus is also associated with sexual receptivity. Mating triggers twice-daily
      PRL surges that supplant the proestrous PRL surge and are responsible for
      maintaining luteal function during the first half of pregnancy. In order to
      understand the neuronal mechanisms controlling the proestrous- and mating-induced
      PRL surges, we examined patterns of Fos expression by immunocytochemistry in
      specific brain regions as a measure of neuronal activity. Intact female rats were
      sacrificed at 09.00, 15.00, and 18.00 h on the day of proestrus and the day of
      diestrus. Brain tissues were also collected at 21.00 h on the day of proestrus
      from rats receiving intromissions or mounts from males or taken directly from
      their homecage. On the day of proestrus, the number of neurons expressing Fos in
      the medial preoptic area (mPOA), medial amygdaloid nucleus (mAMYG), and
      ventromedial nucleus of the hypothalamus (VMH) was few and was associated with
      low plasma PRL levels at 09.00 h; however, the number of Fos-positive cells in
      these brain regions significantly increased at 15.00 and 18.00 h when the
      proestrous PRL surge occurred. Mating during the evening of proestrus resulted in
      a dramatic increase in the number of Fos-positive cells in the mPOA, mAMYG, and
      VMH as well as in the arcuate nucleus (ARC). Nonmated animals in diestrus showed
      low and unchanged PRL levels and Fos expression in all the brain areas throughout
      the day. These results suggest that the mPOA, mAMYG, VMH and ARC may be important
      brain sites for the integration of stimuli associated with proestrous- and mating
      induced PRL surges.

PMID- 10207281
TI  - Sex differences in male-typical copulatory behaviors in response to androgen and
      estrogen treatment in rats.
AB  - The present experiment was performed to test the hypothesis that gender
      differences in the capacity for brain estrogen synthesis could constitute a
      sexually dimorphic mechanism that limits the activational effects of testosterone
      (T) in females, and enhances them in males. We determined the effects of
      treatments with equivalent levels of either T or estradiol (E2) on olfactory
      behavior and mounting in age-matched heterosexually naive gonadectomized male and
      female rats that were genitally ansthetized with lidocaine paste in order to
      minimize the contribution of sexually dimorphic somatosensory inputs to the
      expression of copulatory behavior. We found that T stimulated mounting to a
      greater extent in males than in females, but had equivalent effects on mount
      latency and genital investigation in the two sexes. On the other hand, E2
      stimulated equivalent levels of mounting in males and females and reduced mount
      latency to a similar extent in males and females. However, E2 had a pronounced
      effect on the levels of genital investigation in males but not in females. Serum
      steroid levels and the levels of nuclear steroid receptor occupation in the brain
      were not different between males and females, suggesting that the behavioral
      differences between males and females cannot be attributed to differences in
      peripheral steroid metabolism or brain uptake. The results obtained corroborate
      previous studies suggesting that female rats normally undergo considerable male
      typical behavioral masculinization during fetal development. However, such male
      typical features of normal development in female rats do not extend to the
      regulation of preoptic aromatase activity or to the capacity of females to
      display olfactory behaviors in response to adult E2 exposure, functions which are
      sexually dimorphic even in the rat. The present results support the view that
      gender differences in the capacity for brain estrogen synthesis contribute to the
      sexually dimorphic display of T-stimulated male-typical sexual motivation and
      copulatory behavior in rats.

PMID- 10207283
TI  - An introduction to ethics and quality of life in comprehensive psychiatric
      diagnosis.

PMID- 10207282
TI  - Serotonin in golden hamster testes: testicular levels, immunolocalization and
      role during sexual development and photoperiodic regression-recrudescence
      transition.
AB  - Serotonin (5-HT) is found in the gonads and accessory reproductive organs of
      several species. The golden (Syrian) hamster is a seasonal breeder. Exposure of
      male adult hamsters to short days for 14 weeks results in a severe gonadal
      regression, while after a photoinhibition period of 22 weeks a spontaneous
      testicular recrudescence occurs. The aim of this study was to investigate the
      presence of 5-HT and its major metabolite 5-hydroxyindoleacetic acid (5-HIAA) in
      the gonads of golden hamsters, its immunolocation and its physiological role in
      the testis. The influence of age and photoperiod was also analyzed. Hamsters of
      23, 36, 46, 60 and 90 days of age were kept in long photoperiod (LP: 14:10 h
      light/dark), and adult animals were exposed either to LP or to short photoperiod
      (SP: 6:18 h light/dark) for 14 and 22 weeks. Testicular parenchyma and capsule
      levels of 5-HT and 5-HIAA increased significantly at ages of 36 and 60-90 days,
      but decreased markedly during the exposure of adult hamsters to SP for 14 and 22
      weeks. Mast cells were found exclusively in the testicular capsule. The
      testicular number of mast cells increased concomitantly with age, but decreased
      in adult hamsters exposed to SP. Mast and Leydig cells presented 5-HT-positive
      immunoreactivity. During sexual maturation as well as during the transfer of
      adult hamsters from LP to SP, the 5-HIAA/5-HT ratio showed the highest values in
      active adult animals, indicating that the increase in testicular 5-HT levels in
      adulthood is accompanied by an augment in 5-HT turnover. In vitro basal and hCG
      stimulated testosterone production was significantly inhibited in presence of
      physiological concentrations of 5-HT. In conclusion, the present studies
      demonstrate the existence of 5-HT in mast cells and Leydig cells of hamster
      testes, as well as describe an inhibitory action of this neurotransmitter on
      gonadal testosterone production. Furthermore, the age-dependent and photoperiodic
      related changes detected in testicular 5-HT levels suggest that this
      neurotransmitter might act as an important local modulator of the action of
      gonadotropins on steroidogenesis during sexual development and during the
      photoperiodic regression-recrudescence transition in the golden hamster.

PMID- 10207284
TI  - Qualitative research in diagnostic processes.
AB  - Social sciences, in general, and psychotherapy, in particular, have been informed
      by two fundamentally distinct methodologies of description and explanation:
      firstly, causal nomology based on operationalized data, and secondly, empirical
      hermeneutics focused on the meaningful context of intentions, experiences and
      actions. The paper deals with the second of these two methodologies in the
      context of research on psychotherapeutic diagnosis. This paradigm is a
      methodology for evaluating certain aspects of quality of life which deal with the
      subjective and interpersonal meaning of symptoms.

PMID- 10207285
TI  - Quality of life in psychiatry as an ethical duty: from the clinical to the
      societal perspective.
AB  - It is the aim of this paper to discuss the ethical roots of the concept of
      quality of life and the historical background of its introduction into mental
      health service evaluation research. It will be argued that the original broad
      meaning of the quality of life concept has been brought closely in line with the
      clinical view, neglecting the ethical and the societal dimensions of this
      concept. In conclusion, expansion of the scope of quality of life research in
      psychiatry from a clinical to a societal perspective will be suggested. On the
      basis of this argument, seven research questions concerning the most important
      nonclinical factors influencing the quality of life of mentally ill patients will
      be formulated.

PMID- 10207286
TI  - Ethics and comprehensive diagnosis.
AB  - This paper briefly reviews basic concepts of ethics, including its meanings and
      dimensions and its relationship to culture. It then examines the ethical bases of
      medicine and psychiatry. Of particular relevance here is the connection between
      ethics as concern for totality and the fundamentals of health and healing. Next,
      the ethical bases and implications of clinical diagnosis are considered. Finally,
      the paper outlines the features of a comprehensive diagnostic model and
      explicates how ethics is linked to the integrative nature of comprehensive
      diagnosis and its therapeutic purpose.

PMID- 10207287
TI  - Ethics in psychiatry and psychoanalysis.
AB  - Ethics plays a dual role in psychiatry. The extrinsic role is in defining the
      rules of ethical conduct for the psychiatrist as a professional dealing with
      patients, peers and society at large. The intrinsic role is in defining ethical
      or moral conflict as a determining component in the construction of symptoms of
      mental disorder. Ethical considerations play a role in the truthful description
      of the disorder, diagnosis, dynamic formulation and the doctor-patient
      relationship in treatment. In treatment, there is a need to acknowledge 2
      dimensions of psychological conflict: (1) an appraisal of the actual realistic
      moral conflicts due to symptomatic unethical conduct that goes against one's
      normative conscience, and (2) resolution of past conflicts arising from
      unconscious or repressed aspects of the neurotic conscience or superego, i.e. a
      holdover of unreflected obedience to parental authority. The resolution of past
      and ongoing conflicts promotes growth toward autonomy of moral judgment, free
      choice and moral responsibility.

PMID- 10207288
TI  - Ethics in psychiatric diagnosis from a psychodynamic perspective.
AB  - The diagnostic evaluation, representing a fundamental activity in psychiatric
      practice and research, requires a particular ethical responsibility on the part
      of the clinician. The author proposes the following aspects as being important
      for a comprehensive and ethically sensitive diagnosis: (a) incorporation of the
      patient's subjective perspectives and understanding of his/her disease, (b)
      consideration of the patient's quality of life, (c) assessment of the positive
      aspects of health, (d) awareness of group-dynamic and psychodynamic factors in
      the diagnostic situation, (e) the clinician's professional competence, value
      orientation and personal identity, (f) therapeutic optimism as a basic attitude.
      The patient's active involvement is emphasized since he is the real expert as far
      as his individual, social, religious and ethical needs and values are concerned.

PMID- 10207290
TI  - Carotid endoarterectomy in the presence of contralateral carotid occlusion.
AB  - BACKGROUND: The purpose of this study was to define a correct anesthesiological
      and surgical approach in patient who present a significant carotid stenosis with
      contralateral carotid occlusion. METHODS: Between 1996 and 1998 in our Department
      of Vascular Surgery of the Hospital S. Giovanni Battista has been executed 337
      Carotid Endoarterectomies (CEA). Of these, 44 patient (13%) had a contralateral
      internal carotid occlusion. Forty was male (91%), and 4 female (9%). Echo
      Doppler, angiography, angioTC or angio-RMN and TCD were performed in all
      patients. In all cases was executed a traditional CEA. RESULTS: Because of the
      presence of a large ischaemic cerebral lesion or clamping intolerance 12
      operation were performed under general anesthesia (27%). Shunt was used in 15
      patients (34%) and patch was used in 10 cases (23%). In 2 cases (4.5%) there was
      be a thrombosis of the operated internal carotid artery and one patient died
      (2.3%). CONCLUSIONS: The presence of contralateral internal carotid occlusion
      with carotid stenosis > 70% increase the risk of peroperative stroke because of
      the difficulty of collateral cerebral blood flow. The execution of echo Doppler,
      angiography, angioTC or angioRM and TCD and their evaluation permit to choice the
      best anesthesiological and surgical treatment. The utilization of narcosis with
      thiopental protection and shunting reducing the rate of perioperative stroke, but
      the local anesthesia allows the best monitoring of intraoperative cerebral
      function. This behaviour was correctly when in patient with contralateral
      internal carotid occlusion there is an insufficient intracranic vascularization
      or an extensive ischaemic lesion or clamping intolerance.

PMID- 10207291
TI  - [Deep venous insufficiency of the lower extremities].
AB  - Lower limbs chronic venous insufficiency (CVI) is a widespread pathologic
      condition. Prevalence of venous ulcer in Europe ranges between 0.5% and 1.0%.
      Venous ulceration can be due to insufficiency of the superficial system, although
      deep venous insufficiency is responsible for 75% of the cases. Morbidity and
      socio-economic costs are exceedingly high especially because of frequent
      recurrences. CVI recognises mainly two causes: 1) increased influx, due to
      arteriovenous fistulas; 2) difficult outflow usually secondary to postphlebitic
      or primitive valvular incompetence. The prevalence of CVI and venous ulceration
      is difficult to assess. Surgical treatment tends to cure the underlying
      hemodynamic problem. Homans in 1916 first introduced surgical treatment of CVI
      and venous ulceration: excision of the cutaneous lesion and ligature suprafascial
      of the communicating veins. Since then different various techniques have been
      introduced in the clinical practice: Linton in 1938 supported subfascial
      interruption of the perforating veins but still reported a recurrence rate of
      47%. Stripping of internal saphenous vein associated with division of perforating
      veins is still controversial, because lacks evidence of its real effectiveness in
      preventing recurrences. Felder's surgical technique is preferred by some authors
      to Linton's technique, because of the possibility to divide and section
      incompetent perforating veins without a cutaneous incision in the severely
      diseased postphlebitic tissues. In personal experience (56 patients) treated by
      Felder's techniques, we reached a cutaneous ulceration healing rate of 36% has
      been obtained. Subfascial interruption of perforating veins under endoscopic
      vision associated to the stripping of the internal saphenous vein could be a
      valuable option in the treatment of CVI because of the shorter duration of the
      operation and hospital stay and lesser postoperative complications. Repair and/or
      replacement of deep venous valves, originally described by Kistner in 1968, could
      be curative of venous hypertension due to primitive valvular insufficiency
      (primitive or postphlebitic): the same author in 1975 reported positive results
      (80% at 5 years). Major advantages of indirect valvuloplastic surgical technique
      are: 1) venotomy is not necessary; 2) it does not introduce extraneous material
      in the vasal lumen; 3) clamping of the vein is avoided; 4) heparine or other
      antithrombotic measures are usually not necessary. Although preliminary
      encouraging results, subsequent clinical experiences have demonstrated that
      correction of the reflux of the main axial venous system alone is not curative
      and durable resolution of venous symptoms also depends on the concomitant
      correction of all incompetent perforating veins. Venous valves transplantation is
      theoretically good to correct the deep long reflux and to improve calf pump
      function, although clinical results are still limited and follow-up not prolonged
      enough in terms of symptoms resolution and complete ulcer healing.

PMID- 10207289
TI  - The ethical crisis in psychiatry: consequences for a comprehensive diagnosis and
      therapeutic practice.
AB  - Whereas antipsychiatry left the medical concept of disease and medical
      institutions intact at the turn of the century, this sector was fiercely called
      into question in the subsequent reform efforts. The disclosure that an
      argumentation in terms of pure, exact science was questionable encouraged these
      reform efforts and cast doubt on the objectivism dominant at that time. However,
      in the clinical domain, it also led to a profound crisis of legitimation and thus
      to a crisis in psychiatry's ethical self-conception. The absence of an
      integrative perspective comprising clinical theory and practice became obvious.
      In the future, the basic anthropological preconditions involved in a given
      clinical situation may serve as a guideline.

PMID- 10207292
TI  - [Oxygen consumption during cardiovascular surgery conducted under extra-corporeal
      circulation].
AB  - Whole-body oxygen consumption (VO2) is universally considered both a measure of
      the metabolic activity of the body and an indicator of the adequacy of tissue
      perfusion during cardiopulmonary bypass as well. There is little agreement in the
      literature about the main determinants of oxygen consumption during CPB, except
      for the role of temperature in reducing the metabolic activity of the body. Many
      studies, which have been performed both on animals and in humans, have reached
      some contradictory conclusions about the role of delivery and perfusion flow
      rates, of haemodynamic variables, of the acid-base status, and of drugs
      influencing the variations of oxygen consumption during CPB. Aim of this paper is
      to review the evidences in literature about the determinants of whole-body oxygen
      consumption during cardiopulmonary bypass in man.

PMID- 10207293
TI  - Myocardial infarction caused by compression of anomalous circumflex coronary
      artery after mitral valve replacement.
AB  - We report a case of myocardial infarction after mitral valve replacement
      occurring in a patient with the left cyrcumflex coronary artery arising from the
      right one. The patient underwent mitral valve replacement with a size 27
      Carbomedics prosthesis and a tricuspidal annuloplasty was performed according to
      the De Vega technique. Patient died on the 20th postoperative day.

PMID- 10207294
TI  - [Heparan sulphate in association with indobufen in the treatment of chronic
      peripheral obliterative arteriopathy of the lower extremities. Controlled
      clinical trial].
AB  - BACKGROUND: The aim of this study has been to assess the efficacy and the safety
      of heparansulphate administered with indobufen in the treatment of occlusive
      arterial disease. METHODS: In a controlled open study, nineteen out-patients with
      Fontaine's stage II occlusive arterial disease since one year were randomly
      assigned to treatment with indobufen 200 mg/day or indobufen 200 mg/day and
      heparansulphate 200 mg/day for 6 months. Efficacy assessments were based on
      functional evaluations (pain-free sub-maximal exercise ergometric test, ankle-arm
      pressure ratio at rest and after induced ischemia), on hemocoagulative parameters
      and on physical signs and subjective symptoms assessed monthly over the whole
      period of treatment. All patients but one who was lost to follow-up completed the
      study treatment period as foreseen by the experimental protocol. RESULTS: The
      results of the study show an improvement of 10.89% (day 30), 15.92% (day 60),
      21.04% (day 90), 24.19% (day 120), 25.18 (day 150) 28.84% (day 180) end of study
      in ergometric test pain-free interval obtained by patients treated with
      heparansulphate and indobufen with respect to patients receiving indobufen alone.
      Also hemocoagulative parameters and signs and patients' subjective symptoms were
      positively influenced by the association heparansulphate and indobufen.
      CONCLUSIONS: On the whole, the results of the study indicate that heparansulphate
      in association with antiplatelet therapy with indobufen has a beneficial effect
      in the treatment of peripheral occlusive arterial disease.

PMID- 10207295
TI  - [Value of uroflowmetry in a long-term follow-up study in hypospadias surgery].
AB  - BACKGROUND: Many authors have shown the role of uroflowmetry in the follow-up of
      patients operated on for hypospadias. This technique has also been used to assess
      the validity of the operative technique. METHODS: Sixty patients have been
      selected among those operated on for hypospadias from January 1990 till January
      1996 at the Pediatric Surgery Department of the Second University of Naples,
      Italy. These patients underwent uroflowmetry with a rotating disk sensor at
      clinic. Postoperative time at uroflowmetry ranged between 6 months and 6 years.
      Flow pattern, maximum flow rate (Q max) and mean flow rate (Q ave) were measured.
      Results are expressed as percentiles and compared with those obtained from
      Toguri. Q max and Q ave greater than 25 degrees percentile were considered
      normal; Q max and Q ave between 25 degrees and 5 degrees percentile were
      considered query obstructed; Q max and Q ave below the 5 degrees percentile were
      considered obstructed. RESULTS: Forty-two patients (70%) presented values above
      the 25 degrees centile, 8 patients (13.4%) presented an obstructed-like flow and
      10 children (16.6%) showed a query obstructed flow. Three patients from the
      latter group presented within three months an obstructed-like flow. CONCLUSIONS:
      Uroflowmetry is an important tool in the follow-up of patients operated on for
      hypospadias that are at risk for stenosis and then requiring a further treatment,
      either dilatation or surgery.

PMID- 10207296
TI  - [Williams syndrome without cardiovascular abnormalities].
AB  - In a patient with facial dysmorphic traits, growth deficiency, mental retardation
      but without cardiovascular anomalies, detection of hemizygosity at the elastin
      locus by FISH analysis confirmed diagnosis of Williams Syndrome (WS). To date,
      cardiovascular pathology in WS is thought to be the result of a localized
      response of inelastic vessels to haemodynamic stress in fetal life. Patients with
      deletion at the elastin locus and no cardiovascular defects suggest that genetic
      aspects other than hemizygosity must be investigated, such as transcriptional
      regulation of the elastin gene expression. Moreover, a complete characterization
      of the region commonly deleted in 7q11.23 is needed before excluding other genes
      as responsible for the cardiovascular defects. Clinical investigations are
      requested for selecting patients with partial phenotype, various degrees of
      tissue damage and different evolution at follow-up.

PMID- 10207297
TI  - [Recurrent abdominal pain caused by nodular focal hyperplasia of the liver. A
      case report].
AB  - A case of focal nodular hyperplasia of the liver in childhood (FNH or NRC) is
      reported; a conservative approach is usually preferred in this disease when the
      diagnosis is surely identified, and a follow-up for some years is recommended.
      Despite the increased accuracy of modern imaging methods none of them, singly or
      together, is able to differentiate a malignant lesion with certainty and
      histological confirmation is mandatory. In the case described a laparotomy frozen
      section was performed but it was not possible to make a diagnosis and the liver
      mass was removed. The patient had a complete relief of symptoms with no evidence
      of recurrence in the follow-up. A review of the literature has been made, trying
      to point out this disease and its treatment.

PMID- 10207299
TI  - [Dental pulp diseases. Ultramicroscopic studies].
AB  - After the description of the anatomic and histologic aspects of the healthy
      dental pulp, stress is laid on pulpal pathologies and on the use of
      ultramicroscopic techniques to analyze the cytologic modifications in normal and
      pathologic dental pulp tissues. The results obtained are presented.

PMID- 10207298
TI  - [Science, customs and social life in the classical world].

PMID- 10207300
TI  - [Variations in hemodynamic parameters in patients under general anesthesia
      undergoing submucosal infiltration with a mixture of local anesthetic and
      adrenaline].
AB  - BACKGROUND AND AIMS: Some authors have shown that increased blood levels of
      adrenaline do not have any effect on cardiovascular function. Others have
      documented major changes in arterial blood pressure and heart rate even following
      non-maximal doses of adrenalin in association with anesthetics. The aim of this
      study was to evaluate the toxicity of local anesthetics when used with/without
      associated vasoconstrictors. METHODS: The authors studied the hemodynamic,
      cardiac and respiratory changes in two groups of patients respectively undergoing
      general and local anesthesia for a variety of pathologies of the oro-maxillo
      facial district. At a preoperative stage, 4 ml of mepivacaine (carbocaine) 2%
      with 1:100,000 adrenaline was administered to patients in the first group. Data
      were compared to changes in the same parameters recorded in the second control
      group undergoing local anesthesia for day-hospital surgery who received the same
      quantities of local anesthetic (2 tubes of mepivacaine 2% with 1: 100,000
      adrenaline or 3% without adrenaline). RESULTS: The comparison between the two
      groups of data showed no significant change in cardiorespiratory parameters,
      except in patients with an abnormal response to dentistry stress. CONCLUSIONS: No
      elements were found to support the systemic toxicity of local anesthetic or its
      association with adrenaline.

PMID- 10207301
TI  - A clinical and statistical study of etiologic aspects related to associated tooth
      anomalies in number, size, and position.
AB  - BACKGROUND: The study was aimed to reveal patterns of association among five
      types of dental anomalies (aplasia of second premolars, small size of maxillary
      lateral incisors, infraocclusion of primary molars, ectopic eruption of first
      molars, and palatal displacement of maxillary canines) in an untreated
      orthodontic population, aged 7-14 years. METHODS: The prevalence of associated
      tooth anomalies in five groups of 100 subjects each and characterized by the
      constant presence of one primarily diagnosed dental anomaly was compared to the
      prevalence for the examined dental anomalies in a control group of 1,000
      subjects, deriving from a common initial sample of 4,850 subjects. RESULTS:
      Significant reciprocal associations (p < 0.008) were found among four dental
      anomalies (aplasia of second premolars, small size of maxillary lateral incisors,
      infraocclusion of primary molars, and palatal displacement of maxillary canines),
      suggesting a common genetic origin for these conditions. Ectopic eruption of
      first molars appeared to be a rather separate pathological entity with respect to
      all other examined tooth anomalies. CONCLUSIONS: The statistically demonstrated
      existence of associations among different tooth anomalies is clinically relevant,
      since the diagnosis of those anomalies that appear earlier may indicate potential
      risk for later developing tooth and eruption disturbances.

PMID- 10207302
TI  - Antifungal activity of chlorhexidine containing mouthrinses. An in vitro study.
AB  - BACKGROUND: Oral candidosis has emerged as an increasing problem in
      immunocompromised patients because oral cavity represents an important port of
      entry for systemic fungal infections. METHODS: The aim of the present study was
      to investigate the in vitro antifungal activity of 5 commercial mouthrinses
      containing chlorhexidine (CHX). The Minimum Fungicidal Concentration (MFC)
      against six species of yeasts was determined by a broth macrodilution method. The
      kill-time of mouthrinses at half the concentration of the commercial formulations
      was also determined. RESULTS: MFCs were achieved with each mouthrinses against
      all the organisms under test. However, significant differences in MFC values were
      found for Ebur Os in comparison with Dentosan, Corsodyl and Plak out (p < 0.001).
      Kill-times of Corsodyl and Dentosan were less than or equal to 120 sec with all
      the species of yeasts, except Torulopsis glabrata. Significant differences were
      found in kill-time values between Dentosan and Broxo Din only (p < 0.001).
      CONCLUSIONS: These results suggest that CHX-containing mouthrinses may represent
      an appropriate alternative to conventional antifungal drugs in the management of
      oral candidosis. Effectiveness in preventing systemic fungal infections in
      immunocompromised patients requires further in vivo studies.

PMID- 10207303
TI  - Morphology of peri-implant regenerated bone, in sheep's tibia, by means of guided
      tissue regeneration.
AB  - BACKGROUND: No data on the resistance to functional loads of bone regenerated by
      means of guided tissue regeneration, can be found. In this paper the new-formed
      bone is analyzed, in cases that see the surgical creation of defects in testing
      animals. The morphological aspects of perimplant bone, regenerated by means of
      bone substitutes or not, were evaluated. METHODS: A coronal defect was created by
      means of a counter-sink bur. The following step provided for osseointegrated
      fixtures, with a machined or blasted (TiOblast) surface, to be installed. Some
      bone defects were filled with Bio-Oss, and covered with resorbable membrane
      (Vycril), others were left unfilled. The animals were sacrificed after different
      periods of time (24 and 45 days). Some thick sections (200 microns) underwent
      then microradiography and were examined with a microscope, under transmitted and
      polarized light. Other sections, thin (5 microns), were coloured with toluidine
      blue, Gomori's Stain and Solochrome Cyanine/Congo red. RESULTS: Data confirm the
      excellent behaviour of bovine bone and of TiO blasted fixtures. The experimental
      results bring into evidence that, in cases of Guided Bone Regeneration (GBR) by
      means of membrane, the use of fixtures with a blasted surface (TiOblast), and of
      Bio-Oss as bone substitute, made osseointegration easier. CONCLUSIONS: Results,
      moreover, suggest that in case of implant surgery with GBR, in order to allow the
      maturation of regenerated bone, it's healing time must be prolonged.

PMID- 10207305
TI  - The insulin receptor and metabolic signaling.

PMID- 10207304
TI  - The cystic fibrosis transmembrane conductance regulator and its function in
      epithelial transport.
AB  - CF is a well characterized disease affecting a variety of epithelial tissues.
      Impaired function of the cAMP activated CFTR Cl- channel appears to be the basic
      defect detectable in epithelial and non-epithelial cells derived from CF
      patients. Apart from cAMP-dependent Cl- channels also Ca2+ and volume activated
      Cl- currents may be changed in the presence of CFTR mutations. This is supported
      by recent additional findings showing that different intracellular messengers
      converge on the CFTR Cl- channel. Analysis of the ion transport in CF airways and
      intestinal epithelium identified additional defects in Na+ transport. It became
      clear recently that mutations of CFTR may also affect the activity of other
      membrane conductances including epithelial Na+ channels, KvLQT-1 K+ channels and
      aquaporins (Fig. 7). Several additional, initially unexpected effects of CFTR on
      cellular functions, such as exocytosis, mucin secretion and regulation of the
      intracellular pH were reported during the past. Taken together, these results
      clearly indicate that CFTR not only acts as a cAMP regulated Cl- channel, but may
      fulfill several other cellular functions, particularly by regulating other
      membrane conductances. Failure in CFTR dependent regulation of these membrane
      conductances is likely to contribute to the defects observed in CF. Currently, no
      general concept is available that can explain how CFTR controls this variety of
      cellular functions. Further studies will have to verify whether direct protein
      interaction, specific effects on membrane turnover, changes of the intracellular
      ion concentration or additional proteins are involved in these regulatory loops.
      At the end of this review one cannot share the provocative and reassuring title
      "CFTR!" of a review written a few years ago [114]. Today one might rather finish
      with the statement "CFTR?".

PMID- 10207306
TI  - The IKs channel: coassembly of IsK (minK) and KvLQT1 proteins.

PMID- 10207308
TI  - [Relativization of Amae as a concept--response to the discussion by T. Doi].

PMID- 10207307
TI  - [Sequence of time and relation with others in borderline personality disorder].
AB  - In order to present some new psychopathological explanations on borderline
      personality disorder, the authors made a study on 3 borderline patients who could
      reflectively state their experiences of changes in the sequence of time and the
      relation with others. The following characteristics are considered to be most
      important: 1) They needed someone under their noses who always kept his/her eyes
      upon them. And as soon as they thought that he/she was in close relation with
      them, his/her intensions toward them were taken as already concluded (or
      determined) ones in their subjective experiences. 2) Every-time they found that
      others' intentions were apart from the determined ones, strong rage was evoked in
      them, because they felt that they were betrayed by others. Thus, their painful
      experiences were produced successively. 3) Consequently, they took the whole past
      as congregation of painful experiences, so that they struggled to cut the linkage
      of the present and the past. For that purpose, they tried to plunge head-long
      into momentary experiences. But to complete the purpose, they intensified their
      dependence on others' intentions again as previously stated. This vicious cycle
      itself is thought to be the significant framework of borderline personality
      disorder.

PMID- 10207309
TI  - [Therapy of patients with primary open-angle glaucoma with proxofelin, a combined
      form of proxodolol].
AB  - Effects of an original Russian combined preparation proxofelin consisting of 1%
      proxodolol and 0.25% clofelin solutions on intraocular pressure, ocular
      hemodynamics, pupil size, depth of the anterior chamber, ocular functions,
      arterial pressure, and heart rate were studied in 59 patients (80 eyes) with
      primary open-angle glaucoma. The studies were carried out on day 1 after a single
      instillation of the drug and after 4-8 weeks of its regular use. Obvious
      hypotensive effect on intraocular pressure is due to a significant increase of
      the discharge efficacy coefficient (by 0.06 +/- 0.008) and a 40% suppression of
      aqueous humor production. Comparison of the efficacies of proxofelin and
      proxodolol in primary open-angle glaucoma showed the advantages of the combined
      drug. Unlike cloefelin, the drug was well tolerated.

PMID- 10207310
TI  - [Impact of disorders in blood rheology on progress of glaucoma in patients with
      stable normalized intraocular pressure].
AB  - Comparative study of blood rheology in 53 patients (76 eyes) without
      stabilization of primary glaucoma with normalized intraocular pressure (group 1)
      and in 43 patients (61 eyes) with stabilized course (group 2) showed significant
      differences between the two groups. In group 1 erythrocyte aggregation was
      increased in 79.3% and their deformability decreased in 88.7%; high content of
      Willebrandt's factor was detected in 83% patients. By contrast, in group 2 these
      shifts were detected in only 20.9 and 23.3% patients, respectively, while the
      content of Willebrandt's factor was normal. The detected rheological shifts were
      in high correlation with an unstable course of glaucoma, and their severity may
      serve as a prognostic sign for predicting the course of glaucoma in patients with
      normalized intraocular pressure.

PMID- 10207311
TI  - [Effect of local hypotensive therapy on ocular hemodynamics in patients with
      primary open-angle glaucoma].
AB  - Ocular hemodynamics is followed u p in patients with primary open-angle glaucoma
      after local application of 1% pilocarpine and 0.5% timolol maleate for 30 days.
      Forty-two patients (48 eyes) aged 47-82 years with initial, well-developed, and
      far-advanced condition were followed up. Diastolic, m ean dynamic pressure in the
      orbital artery, and perfusion pressure were measured. A significant decrease of
      diastolic pressure in the orbital artery, more expressed during the first ten
      days was observed in all patients. Later this value increased till the end of
      follow-up, but did not reach the initial level. Hence, patients with visual field
      loss are characterized by a higher local vascular tone and are less liable to its
      decrease after the above local hypotensive therapy.

PMID- 10207312
TI  - [Hyperlipoproteinemias and proteinase inhibitor balance in patients with
      proliferative diabetic retinopathy with solid exudates in retina].
AB  - Studies of lipid metabolism and proteinase inhibitor balance in the blood of
      patients with proliferative diabetic retinopathy (PDR) revealed
      hyperlipoproteinemias (HLP) in 61%. Type IIa HLP predominated (32%), type IV HLP
      were diagnosed in 23%, and type IIb in 7% of cases. Solid exudations in the
      retina were 7 times more frequent in patients with type IV HLP and 5 times more
      frequent in those with type IIb HLP than in patients without HLP. The most
      expressed shifts of proteinase inhibitor balance towards increase of trypsin-like
      activity, which was not compensated for by the antitryptic potential, were
      observed in the same two groups. The data indicate that PDR patients with types
      IIb and IV HLP with increased blood proteolytic activity not compensated for by
      inhibitors are at a high risk of developing solid exudations in the retina.
      Therefore individual drug correction of lipid metabolism and proteinase inhibitor
      balance is recommended for maintaining visual function in diabetics. The
      treatment should be based on the results of clinical and biochemical studies.

PMID- 10207313
TI  - [Heparin inhalations combined with intravenous laser exposure of blood in
      patients with diabetic retinopathy].
AB  - Heparin inhalations combined with intravenous laser exposure of the blood are
      effective in patients with nonproliferative, preproliferative, and proliferative
      diabetic retinopathy. Clinical effect consisted in decrease of edema in the
      macular area, partial resolution of hemorrhages, a tendency to decrease in the
      caliber of veins, improvement of visual acuity, and extension of visual field.
      Immunological studies revealed immunomodulating effect of heparin inhalations and
      intravenous laser exposure of the blood, manifesting by decreased levels of
      pathological circulating immune complexes and increased concentrations of
      immunoglobulins, mainly IgG and IgM. Diabetic hemophthalmia is to be treated by
      subtenon implantation of a collagen system with injection of a prourokinase
      thrombolytic in combination with preoperative preparation including heparin
      inhalations, intravenous laser exposure of the blood, and parabulbar
      administration of 0.5 ml 1% emoxipin for 5 days in order to normalize immune
      hemostatic and redox processes and create conditions for effective action of the
      thrombolytic.

PMID- 10207314
TI  - [Role of kallikrein-kinin system in pathogenesis of eye contusions].
AB  - Studies of the plasma components of the kallikrein-kinin system (KKS) in the
      lacrimal fluid (LF) of damaged eyeball of 32 patients hospitalized for contusion
      for the eyeball showed an appreciable increase of KKS activity during the first
      three days and its less expressed increase on days 10-19 after the injury. The
      content of prekallikrein in the damaged eye LF depends on the severity of eye
      contusion and plasma KKS status, and the levels of LF prekallikrein in the
      damaged and intact eye correlate. Serum kallikrein activity depends on the
      severity of injury.

PMID- 10207315
TI  - [Lymphotherapy of early postoperative period in intraocular cataract correction].
AB  - Potentialities of lymphotropic method of drug administration for arresting
      inflammation after intraocular cataract correction were studied in 60 patients
      aged 48-63 years. Extracapsular cataract extraction with implantation of
      posterior-chamber Alexeev's intraocular lens (IOL) was carried out in all of
      them. Patients with complications of surgery and a history of inflammations in
      the operated eye were not included in the study. For assessing lymphotherapy
      effect on drug concentration in the blood, bloodflow aggregation gradient in the
      bulbar conjunctiva venules was estimated in the operated on eye. The data
      indicate that lymphotherapy is an effective method for treating early
      postoperative inflammations after IOL implantation, shortening the treatment
      terms in comparison with traditional therapy.

PMID- 10207316
TI  - [Study of interferon-inducing activity of para-aminobenzoic acid injected
      subconjunctivally in rabbits].
AB  - Para-aminobenzoic acid (PABA) is an early interferon inductor. The present study
      assesses the interferon-inducing activity of PABA (0.007 and 0.06% solutions) and
      poludan (Poly A:U) injected subconjunctivally to rabbits. Interferon (If) titer
      in the conjunctival washings and anterior chamber humor was assessed 4-48 h after
      injection of If inductors. After the first injection of 0.007% PABA, If titer in
      the conjunctival washings was constantly increasing and reached the maximum after
      48 h (64-128 U/ml). Repeated injection of PABA after 5 days still more stimulated
      the production of If, with the peak after 24 h (128 U/ml); after 48 h the titer
      of If was still high. If titers induced by 0.007% PABA and poludan were
      compatible after both injections in the conjunctiva but not in the anterior
      chamber humor. With poludan, the maximum If titer (16 U/ml) was observed 6 h
      postinjection, after which it was no longer detected, while after PABA the
      maximum If titer (64 U/ml) was observed during the 4th and 12th hours
      postinjection and then decreased, remaining rather high after 24 h. After 0.06%
      PABA, If titers were 2-4 times lower in all experiments than after 0.007% PABA.
      The detected interferon-inducing activity of PABA suggests its therapeutic
      efficacy in ocular diseases involving disorders in If production.

PMID- 10207317
TI  - [Use of liquid crystal eyeglasses for examination and recovery of binocular
      vision].
AB  - A new method for diploptic treatment of strabismus is proposed, based on phase
      division of visual fields using liquid crystal eyeglasses --computer complex. The
      method is based on stereovision training (allowing stereothreshold measurements
      up to 150 ang. sec.). The method was tried in examinations of two groups of
      children: 10 controls and 74 patients with strabismus. Examinations of normal
      controls gave new criteria for measuring fusion reserves and stereovisual acuity
      by the proposed method. The therapeutic method was tried in 2 groups of patients.
      Time course of visual function improvement was followed up by several criteria:
      changes in binocular status by the color test and improvement of in-depth and
      stereoscopic visual acuity. The method is recommended for practice. The authors
      discuss the problem of small angle strabismus.

PMID- 10207318
TI  - [Clinical picture of pure corneal ulcers of different localizations].
AB  - Pure corneal ulcers can be localized at the periphery and in the center.
      Peripheral ulcers are bilateral in 66% and multifocal in 48% cases. They are
      combined with local vasculitis of perilimbic vessels of the conjunctiva. In 84%
      cases the disease occurred in patients with connective tissue and articular
      diseases. Clinical picture of the peripheral corneal ulcer differs from Mourene's
      phagodenic ulcer. Central corneal ulcers are bilateral in 40% patients, are
      associated with primary and secondary "dry eye" syndrome in Sjogren's disease,
      rheumatoid arthritis, systemic vasculitis, Behcet's disease, and in 18% patients
      with cicatricial deformation of the conjunctiva after Stevens-Johnson's syndrome,
      trachoma, and chemical burns of the eyes. Pure corneal ulcers run a chronic
      relapsing course, complicated in one-fourth of patients by corneal perforation
      and secondary infections.

PMID- 10207319
TI  - [On the treatment of dacryocanaliculitis].
AB  - The proposed method for treating dacryocanaliculitis consists in removal of the
      pathological contents blocking the lumen of the involved canaliculus. The
      operation is similar to activation of the lacrimal canal. Canalicular wall mucosa
      is treated with silver nitrate or iodine through a special probe applicator.
      Forty-two patients were treated by this method with good results.

PMID- 10207320
TI  - [Congenital total ectropion of upper lid].
AB  - Two cases with congenital total ectropion of the upper eyelids are reported (1
      bilateral and 1 unilateral). There were no associated ocular or general
      abnormalities nor any apparent causes. One child was born normally, the other by
      cesarean section. The disease is not caused by difficult labor through natural
      birth passages. The condition is usually cured by conservative therapy. If
      surgery is carried out, it should be performed as early as possible in order to
      rule out secondary infections, amblyopia, epidermization of the conjunctiva, etc.

PMID- 10207321
TI  - [Surgical stimulation of uveoscleral discharge in primary glaucoma].

PMID- 10207323
TI  - [Should not we correct some of Donder's assumptions?].

PMID- 10207322
TI  - [Lymphological methods of treatment in ophthalmology].

PMID- 10207324
TI  - Performance of acute flaccid paralysis (AFP) surveillance and incidence of
      poliomyelitis, 1998-1999 (as of 4 March 1999).

PMID- 10207325
TI  - High frequency of therapeutic injections, Republic of Moldova.

PMID- 10207326
TI  - Influenza.

PMID- 10207327
TI  - Ebola: the virus and the disease.

PMID- 10207328
TI  - Progress towards polio eradication, South-East Asia, 1997-1998.

PMID- 10207329
TI  - Guidelines--not always an easy answer.

PMID- 10207330
TI  - Guidelines--not always an easy answer.

PMID- 10207332
TI  - Antimotility agents and E. coli infection.

PMID- 10207331
TI  - Which curriculum?

PMID- 10207333
TI  - The language of suicide.

PMID- 10207334
TI  - Urology: an unfairly neglected discipline of medical training.

PMID- 10207335
TI  - Meta-analysis and adverse drug reactions.

PMID- 10207336
TI  - Privacy policy.

PMID- 10207337
TI  - Autologous versus allogeneic transfusion: patients' perceptions and experiences.
AB  - BACKGROUND: Preoperative autologous donation is one way to decrease a patient's
      exposure to allogeneic blood transfusion. This study was designed to determine
      patients' perceptions about the autologous blood donation process and their
      experiences with transfusion. METHODS: To assess patient perception, a
      questionnaire was administered a few days before surgery to patients undergoing
      elective cardiac and orthopedic surgery in a Canadian teaching hospital. All
      patients attending the preoperative autologous donation clinic during a 10-month
      period were eligible. A convenience sample of patients undergoing the same types
      of surgery who had not predonated blood were selected from preadmission clinics.
      Patient charts were reviewed retrospectively to assess actual transfusion
      practice in all cases. RESULTS: A total of 80 patients underwent cardiac surgery
      (40 autologous donors, 40 nondonors) and 73 underwent orthopedic surgery (38
      autologous donors, 35 nondonors). Of the autologous donors, 75 (96%) attended all
      scheduled donation appointments, 73 (93%) said that they were "very likely" or
      "likely" to predonate again, and 75 (96%) said that they would recommend
      autologous donation to others. There was little difference in preoperative
      symptoms between the autologous donors and the nondonors, although the former
      were more likely than the latter to report that their overall health had remained
      the same during the month before surgery (30 [75%] v. 21 [52%] for the cardiac
      surgery patients and 30 [79%] v. 18 [51%] for the orthopedic surgery patients).
      When the autologous donors were asked what they felt their chances would have
      been of receiving at least one allogeneic blood transfusion had they not
      predonated, the median response was 80%. When they were asked what their chances
      were after predonating their own blood, the median response was 0%. The
      autologous donors were significantly less likely to receive allogeneic blood
      transfusions (6 [15%] for cardiac surgery and 3 [8%] for orthopedic surgery) than
      were the nondonors (14 [35%] for cardiac surgery and 16 [46%] for orthopaedic
      surgery). They were, however, more likely to receive any transfusion (autologous
      or allogeneic) than were the nondonors (25 [63%] v. 14 [35%] for cardiac surgery
      and 31 [81%] v. 16 [46%] for orthopedic surgery). INTERPRETATION: Patients who
      underwent preoperative autologous blood donation were positive about the
      experience and did not report more symptoms than patients who did not donate
      blood preoperatively. Autologous donors overestimated their chances of receiving
      allogeneic blood transfusions had they not predonated and underestimated their
      chances after they had predonated. They were less likely to receive allogeneic
      transfusions, but more likely to receive any type of transfusion, than were
      patients who did not predonate.

PMID- 10207338
TI  - Transfusion practices among patients who did and did not predonate autologous
      blood before elective cardiac surgery.
AB  - BACKGROUND: Preoperative autologous blood donation is commonly used to reduce
      exposure to allogeneic transfusions among patients undergoing elective cardiac
      surgery. However, this technique is associated with an overall increase in
      transfusions (allogeneic or autologous). The authors assessed the impact of
      transfusion decision-making on the effectiveness of preoperative autologous
      donation in reducing the frequency of allogeneic transfusions, and its impact on
      the increased transfusion rate associated with preoperative autologous donation
      in cardiac surgery. METHODS: This retrospective analysis compared transfusion
      practices among 176 patients who predonated autologous blood before elective
      cardiac surgery and 176 matched cardiac surgery patients who did not predonate
      blood. The impact of decision-making on transfusion exposure was determined using
      multivariate analyses to account for major perioperative interventions and
      complications. Odds ratios (ORs) and 95% confidence intervals (CIs) were
      calculated for exposure to allogeneic blood transfusion or any transfusion,
      before and after exclusion of transfusions not conforming with selected
      transfusion criteria. RESULTS: Exposure to allogeneic transfusion was more likely
      among patients who did not predonate blood than among those who did predonate
      blood (OR 14.0, 95% CI 5.8-33.8). This finding was still true after exclusion of
      transfusions not meeting the transfusion criteria (OR 19.3, 95% CI 6.7-55.7). The
      autologous blood donors were more likely than the nondonors to receive any
      transfusion (OR 10.8, 95% CI 5.7-20.3). However, this association was
      substantially attenuated after exclusion of transfusions not meeting the
      transfusion criteria (OR 1.9, 95% CI 1.1-3.2). INTERPRETATION: Patients who
      predonated blood before elective cardiac surgery were at lower risk of receiving
      allogeneic transfusions than the nondonors. This was not because of a deliberate
      withholding of allogeneic transfusions from autologous donors. However, more
      liberal transfusion criteria for autologous blood were largely responsible for
      the increased transfusion rate among the autologous donors.

PMID- 10207339
TI  - Physical abuse during pregnancy: prevalence and risk factors.
AB  - BACKGROUND: Violence during pregnancy is a health and social problem that poses
      particular risks to the woman and her fetus. To address the lack of Canadian
      information on this issue, the authors studied the prevalence and predictors of
      physical abuse in a sample of pregnant women in Saskatoon. METHODS: Of 728 women
      receiving prenatal services through the Saskatoon District public health system
      between Apr. 1, 1993, and Mar. 31, 1994, 605 gave informed consent to participate
      in the study and were interviewed in the second trimester. Of these, 543 were
      interviewed again late in the third trimester. During the initial interview,
      information was collected on the women's sociodemographic characteristics, the
      current pregnancy, health practices and psychosocial variables. The second
      interview focused on the women's experience of physical abuse during the
      pregnancy and during the preceding year, the demographic characteristics and the
      use of alcohol or illicit drugs by their male partner. RESULTS: In all, 31 (5.7%)
      of the women reported experiencing physical abuse during pregnancy; 46 (8.5%)
      reported experiencing it within the 12 months preceding the second interview. Of
      the 31 women 20 (63.3%) reported that the perpetrator was her husband, boyfriend
      or ex-husband. Although all ethnic groups of women suffered abuse, aboriginal
      women were at greater risk than nonaboriginal women (adjusted odds ratio 2.8, 95%
      confidence interval [CI] 1.0-7.8). Women whose partner had a drinking problem
      were 3.4 times (95% CI 1.2-9.9) more likely to have been abused than women whose
      partner did not have a drinking problem. Perceived stress and number of negative
      life events in the preceding year were also predictors of abuse. Abused women
      tended to report having fewer people with whom they could talk about personal
      issues or get together; however, they reported socializing with a larger number
      of people in the month before the second interview than did the women who were
      not abused. INTERPRETATION: Physical abuse affects a significant minority of
      pregnant women and is associated with stress, lack of perceived support and a
      partner with a drinking problem.

PMID- 10207340
TI  - Method of physician remuneration and rates of antibiotic prescription.
AB  - BACKGROUND: Rates of antibiotic prescription in Canada far exceed generally
      accepted rates of bacterial infection, which led the authors to postulate that
      rates of antibiotic prescription depend to some extent on factors unrelated to
      medical indication. The associations between antibiotic prescription rates and
      physician characteristics, in particular, method of remuneration and patient
      volume, were explored. METHODS: The authors evaluated all 153,047 antibiotic
      prescriptions generated by 476 Newfoundland general practitioners and paid for by
      the Newfoundland Drug Plan over the 1-year period ending Aug. 31 1996, and
      calculated rates of antibiotic prescription. Linear and logistic regression
      models controlling for several physician characteristics, specifically age, place
      of education (Canada or elsewhere), location of practice (urban or rural) and
      proportion of elderly patients seen, were used to analyse rates of antibiotic
      prescription. RESULTS: Fee-for-service payment (rather than salary) and greater
      volume of patients were strongly associated with higher antibiotic prescription
      rates. Fee-for-service physicians were much more likely than their salaried
      counterparts to prescribe at rates above the median value of 1.51 antibiotic
      prescriptions per unique patient per year. The association between rate of
      antibiotic prescription and patient volume (as measured by number of unique
      patients prescribed to) was evident for all physicians. However, the association
      was much stronger for fee-for-service physicians. Physicians with higher patient
      volumes prescribed antibiotics at higher rates. INTERPRETATION: In this study
      factors other than medical indication, in particular method of physician
      remuneration and patient volume, played a major role in determining antibiotic
      prescribing practices.

PMID- 10207341
TI  - Drug access among homeless men in Toronto.

PMID- 10207342
TI  - Physical abuse during pregnancy: a significant threat to maternal and child
      health.

PMID- 10207343
TI  - Can the health care system buy better antibiotic prescribing behaviour?

PMID- 10207344
TI  - Tuberculosis: 2. History of the disease in Canada.

PMID- 10207345
TI  - Challenges of prescribing low-dose drug therapy for older people.

PMID- 10207347
TI  - Customers lining up for high-cost hyperbaric therapy.

PMID- 10207346
TI  - Is Internet-based disease management on the way?

PMID- 10207348
TI  - Frozen in time: life in the face of chronic care cutbacks.
AB  - Kathy Cook won the $750 first prize in CMAJ's 7th Annual Amy Chouinard Memorial
      Essay Contest. The deadline for entries to the contest, which is designed to
      stimulate interest in medical writing among journalism students, is June 1.
      Entries should be forwarded to the news and features editor. In her winning
      essay, Cook explores the frustrations and quality-of-life issues that arise in a
      chronic care institution that is trying to operate in the midst of serious
      funding cuts.

PMID- 10207350
TI  - Bupropion (Zyban, sustained-release tablets): reported adverse reactions.

PMID- 10207349
TI  - Link between HIV risk and other STDs debated at forum.

PMID- 10207351
TI  - Adverse drug reaction reporting--1998.

PMID- 10207352
TI  - Immune globulin intravenous products--notice to hospitals.

PMID- 10207353
TI  - Tolcapone (Tasmar)

PMID- 10207354
TI  - Site selection by intestinal helminths of the Virginia opossum (Didelphis
      virginiana).
AB  - Digestive tract helminths of the Virginia opossum (Didelphis virginiana) were
      examined for site specificity and interspecific interactions. Thirty opossums
      were live-trapped at 2 localities in Georgia, killed, and their digestive tracts
      removed and divided into the following sections; esophagus, stomach, small
      intestine (20 equal sections), cecum, and large intestine (5 equal sections).
      Helminths present in each section were identified and counted. Three trematode, 1
      cestode, 2 acanthocephala, and 6 nematode species were found. Two parasites (the
      acanthocephalan Centrorhynchus spinosus and the nematode Viannaia hamata) are new
      state records for Georgia and this is the first report of C. spinosus from an
      opossum. There was considerable overlap between the spatial distributions of many
      of the helminth species found in the small intestine though most species had
      different modal locations. Helminth species locations were unaffected by host sex
      or trapping locality. There was no evidence that the presence, absence, or
      intensity of any helminth species affected the location or intensity of other
      helminth species in the digestive tract.

PMID- 10207355
TI  - A study of the cost effectiveness of selective health interventions for the
      control of intestinal parasites in rural Bangladesh.
AB  - The study examined the cost effectiveness of 4 different regimens in reducing the
      prevalence and intensity of infection of Ascaris lumbricoides, Trichuris
      trichiura, and hookworm over an 18-mo period in randomized community samples of
      children aged 2-8 yr living in rural Bangladesh. The household was the unit of
      randomization in each community. The 4 regimens were (1) only chemotherapy to all
      household members at the commencement of the study (i.e., at an interval of 18
      mo), (2) same as group (1) and regular health education throughout the study
      period, (3) chemotherapy to all household members at the commencement of the
      study and subsequent chemotherapy to all children at intervals of 6 mo, and (4)
      same as group 3 with the addition of regular health education throughout the
      study period. Health education (through home and school visits and focus group
      discussions) was aimed at increasing awareness of worm transmission and the
      disabilities caused by intestinal helminths. Simple ways of improving personal
      hygiene and sanitation through hand washing, nail trimming, wearing of shoes, and
      use of a latrine and clean water supplies were encouraged. Because albendazole is
      a broad spectrum anthelmintic, the cost effectiveness of the 4 interventions were
      compared by the weighted percentage reduction in prevalence and the weighted
      percentage reduction in intensities of infection as measured by geometric mean
      egg loads of all 3 worms combined. The most cost-effective strategy was the
      single albendazole mass chemotherapy at an interval of 18 mo. The 2 regimens
      involving health education were the least cost effective.

PMID- 10207357
TI  - The role of habitat in structuring Halipegus occidualis metapopulations in the
      green frog.
AB  - The transmission dynamics of the trematode Halipegus occidualis in its definitive
      host, Rana clamitans, have been examined over a 5-yr period in a North Carolina
      pond. The breeding season of green frogs coincides with the period of worm
      recruitment, during which time male frogs are territorial and females show strong
      site fidelity. This site fidelity allows inferences to be made regarding the
      suitability of a particular habitat for worm transmission based on frog infection
      intensities within that habitat. Four foci of infection were identified in the
      pond by plotting worm infrapopulation size against site of host capture. Sites
      within infection foci are characterized by shallow water and emergent vegetation,
      factors favorable for overlapping distributions of the 4 hosts in the life cycle
      of H. occidualis. Consistent year-to-year worm prevalences and intensities,
      despite fluctuations in frog population size, are thought to be the result of a
      relatively constant proportion of the frog population being present in infection
      foci each year. Removal of worms from heavily infected frogs in the fifth year
      resulted in further heavy worm recruitment by treated frogs suggesting that site
      selection can predispose a frog to heavy infection. Further, the sum of removed
      parasites and those recruited after parasite removal by treated frog hosts was
      higher than worm infrapopulations observed in previous years, indicating that
      worm density regulates parasite infrapopulation size in heavily infected frogs.

PMID- 10207358
TI  - Distribution and abundance of the tick Ixodes uriae in a diverse subantarctic
      seabird community.
AB  - At Bird Island, South Georgia, we surveyed the distribution and abundance of
      ticks on the vertebrate fauna and found only 1 species Ixodes uriae. We
      classified all seabird species into 3 groups: (1) seabirds nesting on the surface
      of the ground solitarily, in dispersed groups of a few nests, or in colonies with
      well-spaced nests; (2) seabirds nesting on the surface of the ground in dense
      colonies; and (3) seabirds nesting in dense colonies in burrows or rock crevices.
      We detected I. uriae only on 3 species of the second group that nested in large,
      dense, persistent colonies, i.e., black-browed albatross (Diomedea melanophrys),
      gray-headed albatross (Diomedea chrysostoma), and macaroni penguin (Eudyptes
      chrysolophus). Ticks were found on the undersides of the feet on albatrosses but
      not on the undersides of the feet on penguins. We hypothesize that the coarse
      pebble nests of penguins, combined with the fact that their young walk around
      more than albatross young, make the environment on the underside of penguin feet
      more harsh and hostile for ticks than the underside of albatross feet. Despite
      the great abundance of Antarctic fur seals (Arctocephalus gazella) on the island,
      we found no ticks on them.

PMID- 10207356
TI  - Multispecies Plasmodium infections of humans.
AB  - We analyzed point-prevalence data from 19 recent studies of human populations in
      which either Plasmodium ovale or Plasmodium vivax co-occur with Plasmodium
      falciparum and Plasmodium malariae. Although the only statistical interactions
      among, sympatric congeners are pairwise, the frequencies of mixed-species
      infections relative to standard hypotheses of species sampling independence show
      no strong relation to overall malaria prevalence. The striking difference between
      the P. falciparum-P. malariae-P. ovale and the P. falciparum-P. malariae-P. vivax
      data is that the first typically shows a statistical surplus of mixed-species
      infections and the second a deficit. This suggests that the number of Plasmodium
      species present in a human population may be less important in determining the
      frequencies of mixed-species infections than is the identity of those species.

PMID- 10207359
TI  - Mazocraeid monogeneans parasitic on Engraulid fishes in the southwest Atlantic.
AB  - Two species of mazocraeid monogeneans are reported for the first time from
      Argentinean-Uruguayan engraulid fish hosts, Engraulis anchoita and Anchoa marini.
      Mazocraes australis n. sp. collected from the gills of E. anchoita is described:
      this new species can be distinguished from the other congenerics by the number of
      genital hooks in the copulatory organ, the relative size of clamps, and the
      number of hooks in the terminal lappet. Pseudanthocotyloides heterocotyle found
      in the gills of E. anchoita and A. marini is redescribed. The diagnosis of both
      mazocraeid genera are also emended.

PMID- 10207360
TI  - Sialic acid-specific lectin-mediated adhesion of Tritrichomonas foetus and
      Tritrichomonas mobilensis.
AB  - Tritrichomonas foetus is an obligate parasite of the bovine urogenital tract
      producing infection associated with inflammatory changes, abortion, and
      infertility, Tritrichomonas mobilensis was isolated from squirrel monkey colon,
      and symptoms involve diarrheal complications. Both tritrichomonads produced
      hemagglutinins with the properties of sialic acid-specific lectins. Assays on the
      adherence of these protozoans to Chinese hamster ovary (CHO) cells and to bovine
      cervical and monkey colon mucus were performed to assess the function of the
      lectins in adhesion. Sialic acid at concentration as low as 2 mM inhibited the
      adhesion to CHO cells, less effectively to the mucus. Predigestion with
      Clostridium perfringens sialidase prevented the adhesion to both epithelial cells
      and the mucus. Inhibition of endogenous sialidases with 2,3-dehydro-2-deoxy-NeuAc
      increased the adhesion of T. mobilensis to CHO cells. Specific anti-T. foetus
      lectin (TFL) and anti-T. mobilensis lectin (TML) antibodies inhibited adhesion of
      the trichomonads to the epithelial cells and to the mucus. TFL histochemistry
      disclosed the presence of lectin ligands on keratinized vaginal epithelia,
      cervical mucosa, and mucin and on endometrial glands and their secretions. TML
      histochemistry showed reactivity with the luminal membranes of colonic glandular
      epithelium and less with the colonic mucin. Both lectins bound to the surface
      membrane of CHO cells. Anti-lectin antibodies showed granular cytoplasmic and
      strong membrane localization of the lectins in both tritrichomonads. Although the
      2 tritrichomonads have different habitats, the results indicate that both these
      protozoa use lectins with sialic acid specificity for adhesion to mucosal
      surfaces.

PMID- 10207361
TI  - Centrids, a pair of asymmetrically arranged sense organs in Ascaris suum
      (Nematoda, Ascaridoidea).
AB  - Two prominent, asymmetrically placed cuticular somatic sensilla, called centrids,
      are reported in Ascaris suum Goeze, 1782, the pig roundworm. The right centrid is
      situated much more anteriorly on the body than is the left one. The centrids are
      globular in the fourth-stage larva and obviously void of an apical pore,
      suggesting at least a tactile function. In adult worms, the centrids are
      platelike, lacking a globular expansion. The observation on the presence of
      asymmetrically placed centrids in A. suum gives further impetus to the importance
      assigned to sense organs in the classification and identification of nematodes.
      The name centrid was originally chosen to indicate the placement of the papillae
      in the midbody region of worms. The name centrid, rather than, e.g. postdeirid,
      is proposed to be used when denoting asymmetrically oriented midbody sensilla
      among the Ascaridida and papillae, when shown homologous to these, of species
      within the Rhabditea generally. This proposal is in line with the name
      "Mittelkorperpapillen" originally adopted to denote homologous sensillae in
      Cucullanidae (Seuratoidea) by Tornquist in 1931.

PMID- 10207362
TI  - Anti-Trypanosoma brucei activity of nonprimate zoo sera.
AB  - Constitutive anti-Trypanosoma brucei subsp. brucei S 427 clone 1 and 22
      activities were evaluated in sera from 22 species of nonprimate mammals. The sera
      fell into 5 categories. Sera from Cape buffalo, giraffe, and greater kudu showed
      a concentration-dependent inhibition of replication of the 2 clones of organisms,
      which was dependent on the presence of xanthine oxidase. Sera from warthog and
      springbok also severely limited trypanosome replication but lacked xanthine
      oxidase. Their antitrypanosome activity was inactivated by heating at 56 C for 30
      min but not affected by absorbing with trypanosomes at 4 C. Sera from lion and
      leopard showed a concentration-dependent inhibition of the growth of T. brucei
      S427 clone 1 organisms, but not clone 22 organisms. These sera lacked xanthine
      oxidase. Their anti-T. brucei S 427 clone 1 activity was inactivated by heating
      at 56 C for 30 min but not removed by absorbing with trypanosomes. Serum from
      Grant's gazelle prevented replication of both T. brucei clones, lacked xanthine
      oxidase, and was not affected by heating at 56 C. Sera from waterbuck, Thompson's
      gazelle, sitatunga, Cape hartebeeste, gerenuk, Grant's zebra, cow, several cat,
      cougar, bobcat, and domestic cat were fully supportive of trypanosome replication
      irrespective of concentration tested up to a maximum of 48% v/v in culture
      medium. Sera from different individuals of the same mammal species had similar
      effects on trypanosomes, and samples collected from the same individual at
      different times also had similar activities indicating species-specific stable
      expression, or lack thereof, of constitutive serum antitrypanosome components.

PMID- 10207363
TI  - Infectivity and attenuation of Leishmania donovani promastigotes: association of
      galactosyl transferase with loss of parasite virulence.
AB  - During the course of long-term in vitro cultivation of Leishmania donovani
      parasites, the promastigotes were found to lose their infectivity. Lectin
      agglutination studies revealed that there is an up-regulation of terminally
      exposed galactose residues on the noninfective promastigotes. The enzyme
      galactosyl transferase was absent in the infective form but present in the non
      infective form of the parasites. An association between galactosylation and loss
      of infectivity was also observed. We propose that the enzyme galactosyl
      transferase is developmentally regulated and induces galactosylation of surface
      carbohydrates.

PMID- 10207364
TI  - Effects of coinfection with Pomphorhynchus bulbocolli on development of
      leptorhynchoides thecatus (Acanthocephala) in amphipods (Hyalella azteca).
AB  - The effect of the presence of Pomphorhynchus bulbocolli on the development of
      Leptorhynchoides thecatus (Acanthocephala) in amphipod intermediate hosts
      (Hyalella azteca) was examined. Two groups of amphipods were exposed either to
      eggs of both species (experimental) or only to L. thecatus eggs (control).
      Amphipods of both groups were dissected 39 days postexposure. The percentage of
      L. thecatus at the cystacanth stage and mean abundance of cystacanths and
      precystacanths per amphipod were determined. Contingency table analysis and
      Fisher's exact tests demonstrated that a significantly smaller proportion of L.
      thecatus reached the cystacanth stage in coinfected amphipods of the experimental
      group than either worms in the control group or worms in L. thecatus-only
      infections of the experimental group. Interspecific interaction between
      acanthocephalans in intermediate hosts has not been reported previously.
      Coinfection reduces the number of L. thecatus in amphipods available for
      transmission to definitive hosts. Habitat separation by eggs of L. thecatus and
      P. bulbocolli might reduce this effect if amphipods are less likely to become
      coinfected when eggs are in different microhabitats than when they are not.

PMID- 10207365
TI  - Characterization of temperature-sensitive strains of Neospora caninum in mice.
AB  - Temperature-sensitive (ts) strains of the Neospora caninum tachyzoites were
      selected by chemical mutagenesis and selection for growth at 32 C. Three ts
      strains and the parental, N. caninum wild-type strain, NC-1, were examined in the
      present study for their ability to cause disease in inbred BALB/c mice, outbred
      ICR mice, and chemically immunosuppressed ICR mice. In BALB/c mice, all 3 strains
      failed to induce clinical disease, whereas infection with the NC-1 strain caused
      central nervous system disease and death in some mice. No disease was observed in
      ICR mice inoculated with the 3 ts strains or the NC-1 strain. All
      immunosuppressed ICR mice inoculated with the NC-1 strain died, whereas no
      immunosuppressed mice inoculated with the NCts-4 strain and only 1 of 5 mice
      inoculated with the NCts-8 and NCts-12 strains died. The NCts-4 and NCts-12
      strains reverted to a wild-type phenotype when grown at 37 C. Vaccination of
      BALB/c mice with live, but not frozen NCts-8 strain tachyzoites induced
      significant (P < 0.05) protection following NC-1 strain challenge.

PMID- 10207367
TI  - Euryconema brevicauda n. sp. (Oxyurida: Thelastomatidae) a parasite of the mole
      cricket Neocurtilla claraziana (Orthoptera: Gryllotalpidae) in Argentina.
AB  - Euryconema brevicauda n. sp. parasitizing the mole cricket Neocurtilla claraziana
      found in Buenos Aires province, Argentina, is described and illustrated. This
      species is characterized by the male having 3 pairs of genital papillae, 1 pair
      preanal and 2 pairs postanal, and a short, conical-shaped tail.

PMID- 10207366
TI  - Relationships among members of the genus Myxobolus (Myxozoa: Bilvalvidae) based
      on small subunit ribosomal DNA sequences.
AB  - Sequences representing approximately 1,700 base pairs of the 18S rRNA gene from
      10 different species in the genus Myxobolus were found to group them into 3
      clusters that showed little correlation with spore morphology and size or host
      specificity, criteria currently used for both higher and lower taxonomic
      placements in the Myxozoa. Of the phenotypic criteria examined, tissue tropism
      was most correlated with the rRNA groupings observed. Spores of similar size and
      shape (Myxobolus cerebralis vs. Myxobolus squamalis) were distantly related in
      some instances, whereas spores with divergent morphology and size were sometimes
      found to be closely related (M. cerebralis and Myxobolus insidiosus). These
      initial investigations into the phylogenetic relationships of putative members of
      the genus Myxobolus clearly indicate the potential limitations of groupings based
      on size and morphological properties of the spores and host species infected. We
      propose that 18S rRNA gene sequences, combined with information on tissue
      tropism, host species infected, and developmental cycles in the fish and
      alternate host (when and if known) be given greater consideration in taxonomic
      placements of myxosporeans.

PMID- 10207368
TI  - An Eimeriid origin of isosporoid coccidia with Stieda bodies as shown by
      phylogenetic analysis of small subunit ribosomal RNA gene sequences.
AB  - Morphological and life cycle features of the tissue cyst-forming coccidia have
      been difficult to interpret in devising taxonomic classifications for the various
      genera. In this study, we amplified the full small subunit rRNA gene sequence of
      Isospora robini McQuistion and Holmes, 1988, and the partial sequence of Isospora
      gryphoni Olsen, Gissing, Barta, and Middleton, 1998 by PCR. Both of these species
      vary from Isospora species of mammals in having Stieda bodies on the sporocysts.
      The sequences were cloned and sequenced and were incorporated into an alignment
      with other Isospora species lacking Stieda bodies as well as with other coccidia.
      Maximum parsimony analysis of these sequences produced a single most parsimonious
      tree that placed I. robini and I. gryphoni in a clade containing various other
      eimeriid species. The Isospora species lacking Stieda bodies were in the
      sarcocystid clade. Similar results were found by maximum likelihood analysis.
      These findings indicate that the genus Isospora as defined by several authors is
      polyphyletic. Taxonomic changes to the genus Isospora would have to incorporate
      the 2 major clades found by molecular phylogenetic analysis. Isospora species
      with Stieda bodies should be classified in the family Eimeriidae, whereas those
      without Stieda bodies should remain in the family Sarcocystidae.

PMID- 10207369
TI  - Revision of the genus Xiphocephalus and description of Xiphocephalus ellisi n.
      sp. (Apicomplexa: Eugregarinida: Stylocephalidae) from Eleodes opacus
      (Coleoptera: Tenebrionidae) in the western Nebraska Sandhills.
AB  - Xiphocephalus is revised, clarifying diagnosis of the epimerite complex,
      gametocyst, and oocyst. Xiphocephalus ellisi n. sp. (Apicomplexa: Eugregarinida)
      is described from Eleodes opacus (Coleoptera: Tenebrionidae) collected from Keith
      County in the Sandhills of western Nebraska. Measurements are means in
      micrometers. Developing trophozoites solitary; epimerite a complex of terminal
      epimerite and intercalating diamerite: epimerite elongate, ensiform, with
      transverse basal tumidus, length 2-3 times width of basal tumidus; width
      approximately half that of basal tumidus; tumidus toroidal, concavoconcave in
      anterioposterior axis: diamerite roughly cylindrical, no longitudinal fold
      apparent, length approximately twice width. Association late, frontal,
      isogamontic. Protomerite depressed ovoid, length 84.1, width 114.9, anterior
      distance to widest point 50.8. Protomerite-deutomerite septum clearly marked and
      constricted, width 99.3. Deutomerite narrowly obovoid, length 1,094.0, maximum
      width 197.0, anterior distance to widest point 137.8, equatorial width 163.3.
      Total length 1,204.4. Nucleus ellipsoid, length 64.9, width 42.2; typically with
      2-3 polysomal endosomes. Gametocysts roughly spherical, length 376.1, width
      348.2, wall paperlike, papillated, dehiscing by simple rupture, releasing oocysts
      in coiled chains, epispore packet absent, gametocyst residuum present. Oocysts
      brown to black, broadly deltoid, gibbous in lateral aspect, slightly keeled in
      dorsal aspect, length 9.7, height 8.5; with terminal protuberances and a single,
      central, spherical residuum.

PMID- 10207370
TI  - Thysanotaenia congolensis n. sp. (Cestoda: Anoplocephalidae) in the lesser
      savanna cane rat, Thryonomys gregorianus from Democratic Republic of Congo,
      Africa.
AB  - Ten (100%) lesser savanna cane rats, Thryonomys gregorianus, collected from the
      Lake Kivv area of the Democratic Republic of Congo, Africa were found to be
      infected with an undescribed anoplocephalid tapeworm, Thysanotaenia congolensis
      n. sp. Like other species of Thysanotaenia, T. congolensis n. sp. has the ovary
      and vitellarium centrally located, and the egg capsules and testes are
      intervascular. The new species differs from the 2 existing species, Thysanotaenia
      lemuris in lemurs and Thysanotaenia cubensis in humans, in being smaller (34-50
      mm long) and in having a smaller scolex (260-410 microns in diameter), a shorter
      cirrus sac (115 microns long), and smaller eggs (40 microns in diameter).
      Anastomoses of the excretory system and formation of egg capsules in the new
      species are also described.

PMID- 10207371
TI  - Species of Proteocephalus Weinland, 1858 (Cestoda: Proteocephalidae), parasites
      of coregonid and salmonid fishes from North America: taxonomic reappraisal.
AB  - A taxonomic study of species of Proteocephalus Weinland, 1858 (Cestoda:
      Proteocephalidae), from coregonid and salmonid fishes in North America, based
      largely on their type specimens, was carried out. None of the taxa studied
      possesses obvious autapomorphies that would justify its validity. On the
      contrary, all species share the following diagnostic features typical of
      Proteocephalus longicollis (Zeder, 1800) (syn. Proteocephalus exiguus La Rue,
      1911), a polymorphic and widely distributed parasite in the Holarctic: (1) a
      spherical or club-shaped scolex, with sublaterally situated suckers and a
      vestigial but distinct and relatively large apical sucker; (2) the vagina
      possessing a well-developed vaginal sphincter and crossing mostly ventrally the
      proximal part of the cirrus sac; and (3) a long, thick-walled cirrus sac,
      overlapping vitelline follicles medially by more than its proximal half.
      Accordingly, Proteocephalus pusillus Ward, 1910; P. laruei Faust, 1920; "P.
      obtundus" La Rue, 1920 (nomen nudum); P. arcticus Cooper, 1921; P. wickliffi
      Hunter and Bangham, 1933; P. parallacticus MacLulich, 1943; P. californicus
      Haderlie, 1950; P. salmonidicola Alexander, 1951; and P. primaverus Neiland, 1952
      are considered junior synonyms of P. longicollis.

PMID- 10207372
TI  - Sarcocystis dubeyi n. sp. (Protozoa: Sarcocystidae) in the water buffalo (Bubalus
      bubalis).
AB  - Sarcocystis dubeyi n. sp. is proposed for a species forming thick-walled,
      microscopic sarcocysts in striated muscular tissues of the water buffalo (Bubalus
      bubalis). Sarcocysts of S. dubeyi were found in histological sections of skeletal
      muscles and esophagus, but not in heart and tongue, of 8 (13%) of 60 water
      buffaloes examined in Ho Chi Minh City, Vietnam. Sarcocysts of S. dubeyi were up
      to 600 microns long and up to 200 microns wide. The cyst wall was 4.5-9 microns
      thick and was composed of tightly packed, cylindrical villar protrusions (Vp)
      that had a uniform width of up to 3 microns, a length of up to 8 microns, and a
      blunt, often flattened tip. The Vp contained microfilaments but no prominent
      electron-dense granules. The definitive host of S. dubeyi was not determined, but
      it could possibly be humans or other primates. By the present description, 4
      Sarcocystis species are recognized in the water buffalo: the macrocyst-forming
      Sarcocystis fusiformis and S. buffalonis and the microcyst-forming S. levinei and
      S. dubeyi.

PMID- 10207373
TI  - Hydromermis contorta (Kohn) and Hydromermis pseudocontorta n. sp. from
      chironomids of Lake Itasca and Long Lake, Minnesota.
AB  - Hydromermis contorta (Kohn) and Hydromermis pseudocontorta n. sp. are described
      from chironomids in Lake Itasca and Long Lake, Minnesota, respectively. The
      former was recovered from adult females of Glyptotendipes paripes (Edwards) and
      the latter from fourth-instar larvae of Chironomus sp. Hydromermis pseudocontorta
      n. sp. resembles H. contorta in cephalic structures, overall size, and the
      presence of a restricted trophosome in the female. The terminal mouth, long
      uterine and vulvar limbs of the vagina, and the strongly chitinized brownish
      spicule of H. contorta contrast with the subventral mouth, short vaginal limbs,
      and the light yellow spicule of H. pseudocontorta n. sp. Both nematode species
      emerge from the host as sexually mature adults and both species give evidence of
      mating while in the host. The H. contorta described by Welch is designated as a
      new species, Hydromermis albionis n. sp.

PMID- 10207374
TI  - Redescription of Phagicola pithecophagicola Faust, 1920 (Digenea: Heterophyidae),
      the type species of Phagicola Faust, 1920.
AB  - Phagicola pithecophagicola Faust, 1920, the type species of Phagicola Faust, 1920
      (Trematoda: Heterophyidae: Phagicolinae), is redescribed on the basis of
      examination of type specimens (syntypes) from the monkey-eating eagle,
      Pithecophaga jeffreyi, from the Philippines. The oral sucker is armed with 1
      complete row of 16 circumoral spines (10-19.5 microns long by 4-8 microns wide)
      and 4 accessory spines (5.5-8 microns long by 3-4 microns wide) on the dorsal
      side; this arrangement differs from the original description and later
      redescriptions, where only 12 circumoral spines in 1 row were reported. The
      ventrogenital sac contains a ventral sucker and a large gonotyl with 2 small,
      often indistinct, lobes containing a few refractile bodies. The intestinal ceca
      extend reaching down to the ovarian level. The uterus is confined to the
      acetabulo-ovarian region, and eggs are 17-20 microns long by 9-10 microns wide.

PMID- 10207375
TI  - Echinococcus multilocularis coproantigen detection by enzyme-linked immunosorbent
      assay in fox, dog, and cat populations.
AB  - A sandwich enzyme-linked immunosorbent assay (ELISA) for the detection of
      Echinococcus multilocularis coproantigens (EM-ELISA) was developed with
      polyclonal rabbit (solid phase) and chicken egg (catching) antibodies that were
      directed against E. multilocularis coproantigens and somatic worm antigens,
      respectively. In experimentally infected dogs and cats, coproantigens were first
      detectable 6-17 days postinfection (PI) in samples of 8 dogs (worm burdens at
      necropsy: 6,330-43,200) and from 11 days PI onward in samples of 5 cats infected
      with 20-6,833 worms. After anthelmintic treatment of 4 dogs and 5 cats at day 20
      PI, coproantigen excretion disappeared within 3-5 days. The sensitivity of the
      ELISA was 83.6% in 55 foxes infected with 4-60,000 E. multilocularis, but reached
      93.3% in the 45 foxes harboring more than 20 worms. The EM-ELISA was used in
      surveys of "normal" dog and cat populations in Switzerland. Among 660 dogs and
      263 cats, 5 dogs and 2 cats exhibited a positive reaction. In 2 of these dogs
      (0.30%) and 1 cat (0.38%), intestinal E. multilocularis infections were confirmed
      by necropsy, polymerase chain reaction PCR, or both. The specificites of the
      ELISA in these groups were found to be 99.5% and 99.6%, respectively, if positive
      ELISA results that could not be confirmed by other methods were classified as
      "false positive" reactions.

PMID- 10207377
TI  - Congenital Baylisascaris sp. larval migrans in a newborn lamb.
AB  - A 3-day-old domestic lamb, moribund since birth, was submitted as part of a
      diagnostic effort concerning weak newborn lambs due possibly to congenital
      Bluetongue virus infection. Gross lesions were consistent with such an event.
      Histologic examination of cerebrum and cerebellum revealed multiple granulomas,
      the age of which required prenatal development. These contained larvae compatible
      with those of Baylisascaris sp. This finding together with evidence that parents
      of children with neural larval migrans have been seropositive for ascarid antigen
      suggests that mammalian fetuses in general should be added to the list of those
      at risk for neural larva migrans due to ascarid parasites.

PMID- 10207376
TI  - Serological diagnosis of Parelaphostrongylus tenuis infection in white-tailed
      deer and identification of a potentially unique parasite antigen.
AB  - Serological diagnosis of Parelaphostrongylus tenuis infection should offer many
      advantages over the currently used method of fecal analysis that relies on a
      patent infection. Toward this end, we investigated the presence of P. tenuis
      specific antibodies in experimentally infected white-tailed deer (WTD) and of
      unique P. tenuis antigens that may be exploited for serodiagnosis. WTD infected
      with 6, 20 or 100-150 P. tenuis third-stage larvae (L3) had anti-parasite
      antibodies from as early as 21 days postinoculation (dpi) until the end of the
      experiment (147 dpi). Peak anti-P. tenuis enzyme-linked immunosorbent assay
      (ELISA) titers in individual animals ranged from 1:70 to 1:5,700. Serum from
      infected WTD reacted with 5 distinct P. tenuis L3 antigens (105, 45, 37, 32, and
      19 kDa) as detected by the immunoblotting technique. Serum from caribou infected
      with Parelaphostrongylus andersoni or Elaphostrongylus rangiferi reacted with all
      antigens except the 37-kDa antigen of L3, indicating that it may be unique to P.
      tenuis and can serve as a serodiagnostic antigen. The 37-kDa antigen appears to
      be present in the adult P. tenuis but not adult E. rangiferi or E. cervi. The
      development of an ELISA utilizing the unique antigen of P. tenuis should lead to
      a reliable diagnostic assay for P. tenuis infection in WTD.

PMID- 10207378
TI  - Development and proliferation of Trypanosoma musculi in the presence of adherent
      splenic cells.
AB  - The development and proliferation of Trypanosoma musculi parasites were studied
      in vitro in the presence of adherent splenic cells. The parasites grew and
      proliferated only when attached by their flagellar tips to adherent splenic
      cells. Analyses of excretory-secretory products of the adherent cells-parasites
      did not indicate any detectable soluble growth factor that might be responsible
      for the growth of these trypanosomes. During the proliferation, the kinetoplast
      migrated toward the nucleus, and once in the vicinity of the nucleus, nuclear
      division was triggered. The nucleus and kinetoplast divided at the same time
      Trypanosoma musculi parasites started dividing from their flagellar ends, and
      daughter cells were formed within 48 hr. In the absence of adherent splenic cells
      in vitro, the parasites were transformed into round nonviable forms.

PMID- 10207379
TI  - An infestation of the mite Sancassania berlesei (Acari: Acaridae) in the external
      auditory canal of a Korean man.
AB  - We here report the case of a storage mite, Sancassania berlesei, infestation in
      the external auditory canal of a 46-yr-old male. He complained of feeling a
      foreign body and itching in the left external auditory canal for 1 mo, with
      accompanying otalgia for 3 days. Considering the duration of the patient's
      complaint and the 8-9-day life cycle of the mite, the mites are believed to have
      lived in the patient's ear for more than 3 generations.

PMID- 10207380
TI  - Discapseudes holthuisi (Crustacea: Tanaidacea) as an intermediate host of
      Caballerorhynchus lamothei (Acanthocephala: Cavisomidae).
AB  - The intermediate host of the acanthocephalan Caballerorhynchus lamothei Salgado
      Maldonado, 1977, is reported for the first time. Cystacanths of C. lamothei were
      found in the hemocoel of the tanaid shrimp Discapseudes holthuisi Bacescu and
      Gutu, 1975, in Alvarado and Sontecomapan lagoons, Veracruz, Mexico. This is the
      first report of a palaeacanthocephalan using a tanaid shrimp as an intermediate
      host. Prevalence by locality, shrimp length, sex and developmental stage, and an
      analysis of the distribution of number of cystacanths per host are presented. A
      higher prevalence, and percentage of multiple infections and larger host size
      were found in Alvarado Lagoon.

PMID- 10207381
TI  - Stock cultures of free-living amebas: effect of temperature on viability and
      pathogenicity.
AB  - The effect of temperature on the viability and pathogenicity of free-living
      amebas during long-term storage were carried out for 34 mo at room temperature,
      40 mo at +4 C, and 15 mo at -15 C. During long-term storage, pathogenic amebas
      tend to lose their virulence. Acanthamoeba showed better survival potential than
      Naegleria.

PMID- 10207382
TI  - The life cycle of a horsehair worm, Gordius robustus (Nematomorpha: Gordioidea).
AB  - Aspects of the life cycle of the nematomorph Gordius robustus were investigated.
      Gordius robustus larvae fed to Tenebrio molitor (Coleoptera: Tenebrionidae)
      readily penetrated and subsequently encysted in the posterior portion of the
      midgut wall. Parasite development was then arrested in each infected beetle. Upon
      feeding these cysts to laboratory-reared Gryllus firmus, worm larvae developed to
      adults in the cricket hemocoel. In an additional experiment, G. robustus larvae
      fed to G. firmus did not develop to adults. These findings are in contrast to
      other studies that found direct infection to be an alternative mode of infection.
      This experiment is the first employing a laboratory-maintained stock of hosts to
      rear nematomorph worms.

PMID- 10207383
TI  - Clinical and serologic evaluation of two llamas (Lama glama) infected with
      Toxoplasma gondii during gestation.
AB  - Two pregnant llamas (Lama glama) infected with Toxoplasma gondii and their
      offspring were evaluated clinically and serologically. Llama 1 was inoculated
      orally with 1,000 infective occysts of the P89 strain of T. gondii at 82 days of
      gestation (DOG). Llama 2 became naturally infected with T. gondii between 26 and
      119 DOG. Both llamas remained clinically normal and delivered healthy offspring.
      Sera collected from both llamas during pregnancy and from their offspring before
      and after colostral ingestion were evaluated for antibodies to T. gondii by the
      modified agglutination test (MAT), latex agglutination test (LAT), indirect
      hemagglutination test (IHAT), and the Sabin-Feldman dye test (DT). In llama 1,
      MAT antibody titers were < 1:20, 1:320, 1:1,280, 1:640, and 1:80 at 82, 97, 109,
      132, and 152 DOG, respectively. The MAT titers in naturally infected llama 2 were
      < 1:32, 1:320-1:640, and 1:1,280 at 26, 119-200, and 346 DOG, respectively. In
      both llamas, antibody titers in the DT were of similar magnitude as the MAT, but
      titers in the LAT and IHAT were inconsistent. Antibodies to T. gondii were not
      detected in precolostral sera obtained from offspring of both llamas suggesting
      there was no fetal T. gondii infection.

PMID- 10207385
TI  - Mesostigmatid mite infestations of rodents in diverse biotopes of central and
      southern India.
AB  - Examination of 165 rodents trapped in domestic, peridomestic, and feral biotopes
      of central and southern India revealed the presence of 1,359 mesostigmatid mites.
      Rodents in central India were infested with 1 species of mite, Laelaps nuttalli;
      98% of these mites were recovered from the peridomestic rodent Bandicota
      bengalensis. Material from the burrow nest of a peridomestic rodent examined in
      central India revealed the mite, Hypoaspis miles. Rodents from the diverse
      biotopes of southern India were infested by 8 species of mites: L. nuttalli,
      Laelaps buxtoni, Laelaps myonyssognathus, Androlaelaps aduncus, Androlaelaps
      marshalli, Androlaelaps sp. A, Hypoaspis sp. 1, and Hypoaspis sp. 2. Sheep from
      nearby villages regularly graze in feral biotopes. From the hair of these sheep,
      2 species of mesostigmatid mites were recovered, A. aduncus and A. marshalli. The
      sheep appeared to aid the dispersal of rodent-infesting mites passively. Laelaps
      nuttalli was the predominant mite species found on the peridomestic rodent B.
      bengalensis. In both central and southern India, the prevalence, mean intensity,
      and relative density of this mite were much higher on peridomestic rodents than
      on domestic and feral rodents. A significant negative correlation was found
      between the numbers of mites and fleas infesting rodents in central India. A
      highly significant positive association between A. marshalli and A. aduncus on
      the feral rodent Tatera indica was recorded. In southern India, the overall
      prevalence of the 8 species of mites was highest on Mus platythrix. However, the
      combined prevalence of these mites on 2 feral rodents T. indica and M. platythrix
      was lower than their prevalence on B. bengalensis. Similarly, the combined values
      for mean intensity and relative density of these mites on the 2 feral rodents
      were lower than on the peridomestic rodent B. bengalensis.

PMID- 10207384
TI  - Freeze tolerance, morphology, and RAPD-PCR identification of Trichinella nativa
      in naturally infected arctic foxes.
AB  - Arctic foxes (Alopex lagopus) were collected from Greenland and Svalbard (N =
      319). Twenty-four were infected with Trichinella (7.5%). Molecular analysis
      (random-amplified polymorphic DNA polymerase chain reaction) confirmed that all
      animals were infected with Trichinella nativa. Motile larvae were found in muscle
      tissue from all foxes after carcasses had been frozen for 1 yr at -18 C.
      Infective larvae were found in 2 foxes after a total of 4 yr storage at -18 C,
      which is longer than any previous observations. Morphological examination of the
      cysts showed large nurse cells and significant deposition of collagen and
      connective tissue. It is suggested that, within the geographical distribution of
      T. nativa, the more freeze-resistant isolates are found at higher latitudes.

PMID- 10207386
TI  - Species of Proteocephalus Weinland, 1858 (Cestoda: Proteocephalidae) from
      cyprinid fishes in North America.
AB  - A taxonomic study of Proteocephalus species parasitizing cyprinid fishes in North
      America, namely Proteocephalus ptychocheilus Faust, 1920 and Proteocephalus
      cobraeformis Haderlie, 1953, has demonstrated their conspecificity with
      Proteocephalus torulosus (Batsch, 1786), a common parasite of cypriniform fishes
      (Cyprinidae and Cobitidae) in the Palaearctic Region. Proteocephalus
      ptychocheilus and P. cobraeformis are considered junior synonyms of P. torulosus.

PMID- 10207387
TI  - Biallelic polymorphism in the intron region of beta-tubulin gene of
      Cryptosporidium parasites.
AB  - Nucleotide sequencing of polymerase chain reaction amplified intron region of the
      Cryptosporidium parvum beta-tubulin gene in 26 human and 15 animal isolates
      revealed distinct genetic polymorphism between the human and bovine genotypes.
      The separation of 2 genotypes of C. parvum is in agreement with our previous
      genotyping data based on the thrombospondin-related adhesion protein (TRAP-C2)
      gene, indicating these genotype characteristics are linked at 2 genetic loci.
      Characterization of Cryptosporidium muris and Cryptosporidium serpentis has
      further shown that non-parvum Cryptosporidium parasites have beta-tubulin intron
      sequences identical to bovine genotype of C. parvum. Thus, results of this study
      confirm the lineage of 2 genotypes of C. parvum at 2 genetic loci and suggest a
      need for extensive characterization of various Cryptosporidium spp.

PMID- 10207388
TI  - Reevaluation of the taxonomic status of Halipegus occidualis Stafford, 1905
      (Digenea: Hemiuridae).
AB  - In response to confusion regarding the taxonomy of halipegines inhabiting North
      American amphibians, the reproductive structures of the hemiurid Halipegus
      occidualis are described from adult worms reared from cercariae shed by Helisoma
      anceps from Charlie's Pond, North Carolina. The report of a Laurer's canal is
      confirmed and the presence of a canalicular seminal receptacle established. The
      suggestion that H. eccentricus Thomas, 1939 be considered a junior synonym of H.
      occidualis Stafford, 1905 is rejected.

PMID- 10207389
TI  - What really constitutes moderate dieting and health-promoting behaviors.

PMID- 10207390
TI  - Setting the nation's health agenda.

PMID- 10207391
TI  - ADA helps Shape Healthy People 2010; update on healthy weight partnership
      guidelines; regulatory comments.

PMID- 10207392
TI  - Look before you leap--but do leap!

PMID- 10207393
TI  - The Lewin Group Study--what does it tell us and why does it matter? [ comment].

PMID- 10207394
TI  - The estimated costs and savings of medical nutrition therapy: the Medicare
      population.
AB  - OBJECTIVES: To measure the potential savings from medical nutrition therapy (MNT)
      and to estimate the net cost to Medicare of covering these services for Medicare
      enrollees. This includes developing an estimate of the cost of providing medical
      nutrition services to the Medicare population and estimating the savings in
      hospital and other spending resulting from the use of these services. DESIGN:
      Analysis of longitudinal data from the Group Health Cooperative of Puget Sound
      (Seattle, Wash) for persons aged 55 years and older who have coverage for MNT
      services. SUBJECTS/SETTING: Persons aged 55 years and older who had diabetes (n =
      12,308), cardiovascular disease (n = 10,895), or renal disease (n = 3,328) and
      who were covered under the Group Health Cooperative of Puget Sound, including
      Medicare beneficiaries enrolled in the plan's Medicare risk contract program.
      Extrapolation to the US Medicare population is based on data for persons served
      by the Group Health Cooperative of Puget Sound. INTERVENTION: The use of MNT.
      MAIN OUTCOMES MEASURE: Differences in health care utilization levels of persons
      with diabetes, cardiovascular disease, and renal disease who do and do not
      receive MNT. Differences in utilization were estimated for hospital discharges
      per calendar quarter, physician visits per quarter, and other outpatient visits
      per quarter. STATISTICAL ANALYSES PERFORMED: Multivariate regression models of
      changes in utilization for persons after they receive MNT services. RESULTS: Our
      analysis showed that MNT was associated with a reduction in utilization of
      hospital services of 9.5% for patients with diabetes and 8.6% for patients with
      cardiovascular disease. Also, utilization of physician services declined by 23.5%
      for MNT users with diabetes and 16.9% for MNT users with cardiovascular disease.
      The net cost of covering MNT under Medicare is estimated to be $369.7 million
      over the 1998 through 2004 period. The total cost of benefits is estimated to be
      $2.7 billion over this period. This would be partially offset by estimated
      savings of $2.3 billion resulting in net costs of $369.7 million. The program
      would actually yield net savings after the third year of the program, which would
      continue through 2004 and beyond. CONCLUSION: After an initial period of
      implementation, coverage for MNT can result in a net reduction in health services
      utilization and costs for at least some populations. In the case of persons aged
      55 years and older, the savings in utilization of hospital and other services
      will actually exceed the cost of providing the MNT benefit. These results suggest
      that Medicare coverage of MNT has the potential to pay for itself with savings in
      utilization for other services.

PMID- 10207395
TI  - Soft drink consumption among US children and adolescents: nutritional
      consequences.
AB  - OBJECTIVE: To determine whether carbonated soft drink consumption is associated
      with consumption of milk, fruit juice, and the nutrients concentrated in these
      beverages. DESIGN: Data collected as part of the 1994 Continuing Survey of Food
      Intakes by Individuals were analyzed. Information on food and nutrient intake was
      derived from 2 days of dietary recall data collected via an in-person interview.
      SUBJECTS AND PARTICIPANTS: Nationally representative sample of people of all ages
      residing in the United States (response rate = 76.2%). Analyses were restricted
      to children aged 2 to 18 years (N = 1,810). STATISTICAL ANALYSES PERFORMED:
      Logistic regression analyses were conducted to predict the odds of low milk and
      juice consumption by soft drink consumption level. To determine whether intake of
      select nutrients varied by soft drink consumption, multiple linear regression
      modeling was conducted. Analyses were conducted using sample weights and software
      appropriate for the survey design. RESULTS: Energy intake was positively
      associated with consumption of nondiet soft drinks. For example, mean adjusted
      energy intake was 1,830 kcal/day for school-aged children who were nonconsumers
      of soft drinks compared with 2,018 kcal/day for children in this age group who
      consumed an average of 9 oz of soda or more per day. Those in the highest soft
      drink consumption category consumed less milk and fruit juice compared with those
      in the lowest consumption category (nonconsumers). CONCLUSIONS: Nutrition
      education messages targeted to children and/or their parents should encourage
      limited consumption of soft drinks. Policies that limit children's access to soft
      drinks at day care centers and schools should be promoted.

PMID- 10207397
TI  - Knowledge, attitudes, and behaviors of college students regarding the 1990
      Nutrition Labeling Education Act food labels.
AB  - OBJECTIVES: This study examined the influence of 1990 Nutrition Labeling and
      Education Act food labels on college students. The purposes of the study were to
      examine knowledge, attitudes, and behaviors of college students regarding labels
      and relationships among these factors, and whether educational experience with
      labels was associated with label-reading knowledge, attitudes, and behaviors.
      DESIGN: A descriptive, nonexperimental research design was used. Data were
      gathered using a survey designed for the study. SUBJECTS: The study surveyed 208
      undergraduate students enrolled in general education classes at a midwestern
      university. STATISTICAL ANALYSIS: Descriptive statistics analyzed knowledge,
      attitudes, and behaviors of college students regarding food labels. The Student t
      test and chi 2 analysis evaluated specific measures of behavior. Pearson
      correlation coefficients and multiple regression analysis examined relationships
      among variables and identified factors associated with label use. RESULTS:
      Students' mean knowledge score was 48%. Knowledge score was positively correlated
      with attitudes toward labels (r = .14, P = .04) and use of labels (r = .87, P =
      .0001). Previous education in reading labels was associated with higher knowledge
      scores (P = .04). Ninety-five percent of participants perceived the label to be
      useful, but many distrusted nutrition claims. Seventy percent looked at the
      Nutrition Facts label when purchasing a product for the first time. The single
      best predictor of general label use was a positive attitude toward labels (P <
      .001), followed by being a woman (P < .01). CONCLUSIONS: The 1990 National
      Labeling and Education Act food label has influenced college students. Labeling
      education efforts are associated with greater knowledge about labels, more
      favorable attitudes toward them, and increased label use in making food choices.
      Special attention should be directed toward explaining terms and phrases on
      labels and the guidelines that ensure truthfulness of nutrition claims. College
      students need to understand their need for numerous nutrients instead of merely
      focusing on the fat and caloric content of foods.

PMID- 10207396
TI  - The effect of eating out on quality of diet in premenopausal women.
AB  - OBJECTIVE: To compare the intake of women who report varying levels of frequency
      of consuming food at commercial facilities outside the home. DESIGN: A 1-week
      descriptive study of dietary intake in women. Subjects completed daily diet
      records that included information regarding the source of the food eaten at each
      meal or snack. The sample was divided on the basis of the number of meals each
      subject reported obtaining from a commercial establishment outside the home. Of
      the 129 subjects, 56% (n = 72) reported eating out 5 times or less during the
      week of recording (Low Eating Out group) and the remainder (n = 57) reported
      eating out between 6 and 13 times (High Eating Out group) SUBJECTS/SETTING: One
      hundred twenty-nine premenopausal women were recruited via community advertising
      for an investigation of health habits. This study was conducted in a midsouthern
      US city. STATISTICAL ANALYSES PERFORMED: Results were analyzed using independent
      sample t tests and chi 2 tests. RESULTS: Mean intake was compared for the groups.
      The High Eating Out group was found to be consuming significantly more total
      energy (2,057 kcal vs 1,769 kcal; P = .002), fat (79.5 g vs 60.6 g; P < .001),
      and sodium (3,299 mg vs 2,903 mg; P = .043) and marginally more carbohydrate
      (261.5 g vs 234.6 g; P = .055) and protein (71.5 g vs 65.4 g; P = .066). Total
      fiber or calcium intake did not differ between the groups. CONCLUSIONS: Our study
      demonstrates that women who report eating out a greater number of times per week
      report more total energy intake as well as higher fat and sodium intakes.
      However, the High Eating Out group did not consume significantly more fiber or
      calcium in the extra energy consumed.

PMID- 10207398
TI  - Identification of risk factors for delayed onset of lactation.
AB  - OBJECTIVE: To identify infant feeding, socioeconomic, demographic, and delivery
      related factors that affect women's self-reported timing of the onset of
      lactation. DESIGN: Longitudinal survey of women from day 1 postpartum until self
      reported onset of lactation. Subjects were interviewed in person on day 1
      postpartum, then surveyed daily by telephone regarding infant feeding method,
      breast symptoms, and perception of whether the onset of lactation had occurred.
      Medical records were reviewed. SUBJECTS/SETTING: Data were collected from 192
      women after they gave birth to a healthy, term singleton. STATISTICAL ANALYSES
      PERFORMED: chi 2 Analyses were used to identify variables associated with delayed
      onset of lactation (onset of lactation > or = 72 hours postpartum). Multivariate
      logistic regression was used to identify the independent association of each
      significant variable with delayed onset of lactation. RESULTS: Risk factors for
      delayed onset of lactation included white/Hispanic ethnicity, heavy/obese body
      build, delivery of offspring by unscheduled cesarean delivery, vaginal delivery
      with prolonged stage 2 labor, infant birth weight less than 8 lb, and exclusive
      formula-feeding before the onset of lactation. APPLICATIONS/CONCLUSIONS: Women
      who are at risk for delayed onset of lactation need additional breast-feeding
      support during the first week postpartum. During their hospitalization, these
      women should be instructed about the normal lactation process and the possibility
      that onset of lactation may occur later than 72 hours postpartum. Frequent
      nursing should be recommended, as delayed onset of lactation was associated with
      the lack of infant suckling.

PMID- 10207399
TI  - Early introduction of solid foods among urban African-American participants in
      WIC.
AB  - OBJECTIVE: To compare infant feeding practices among low-income, urban, African
      American women enrolled in the Special Supplemental Nutrition Program for Women,
      Infants, and Children (WIC) with current recommendations for infant feeding.
      DESIGN: Longitudinal follow-up of women and their infants who participated in a
      WIC-based breast-feeding promotion project. Women enrolled prenatally at or
      before 24 weeks of gestation were followed up until 16 weeks postpartum.
      SUBJECTS/SETTING: Two hundred seventeen African-American WIC participants in an
      urban area. METHODS: Data related to infant feeding practices were collected by
      interviewers who used a structured questionnaire to determine when nonmilk
      liquids or solids were introduced to the infant. Reported practices were compared
      with current recommendations. STATISTICAL ANALYSIS PERFORMED: Contingency table
      analysis, including chi 2 tests, and multivariate analysis using logistic
      regression. RESULTS: By 7 to 10 days postpartum, approximately a third of infants
      were receiving some nonmilk liquids or solids; this escalated to 77% by 8 weeks
      and 93% by 16 weeks postpartum. Women breast-feeding exclusively (i.e., not
      adding nonmilk liquids or solids) were least likely, and women providing mixed
      feeding (breast milk and formula) were more likely, than women feeding formula
      exclusively to introduce nonmilk liquids and solids at each data collection time
      period. APPLICATIONS/CONCLUSIONS: WIC participants who receive instruction about
      infant feeding nutrition are no more likely than mothers who do not participate
      in WIC to follow infant feeding guidelines recommended by the American Academy of
      Pediatrics in regard to the time when solids should be introduced to infants'
      diet. Our findings suggest the need for WIC to implement more powerful and
      innovative educational and motivational strategies to help mothers delay the
      introduction of nonmilk liquids and solid foods until their infants are 4 to 6
      months old, as recommended.

PMID- 10207400
TI  - Primary care providers need a variety of nutrition and wellness patient education
      materials.
AB  - OBJECTIVE: To assess and document the need for nutrition and wellness patient
      education materials. DESIGN: The results of open-ended interviews and focus
      groups were used to develop a mail-type survey. The 46-item survey addressed
      barriers to using nutrition and wellness education materials as well as format,
      education/reading level, foreign languages, and topics needed. North Carolina
      Cooperative Extension Service (NCCES) family and consumer education agents
      distributed surveys to family and general practices throughout North Carolina.
      SUBJECTS: Of the 721 primary care providers surveyed, 303 (42%) returned usable
      surveys. Respondents practiced in 89 of the 100 counties of the state served by
      NCCES family and consumer education agents. STATISTICAL ANALYSIS PERFORMED:
      Descriptive statistics and independent sample t tests were used to analyze survey
      results. RESULTS: Limited time with patients and inability to obtain materials
      because of cost or being unsure of sources were most often identified as barriers
      to using nutrition and wellness materials. Of the 26 topics surveyed, 6 had mean
      levels of need greater than or equal to high need (mean score > or = 4): weight
      control for adults, smoking cessation, changing dietary fat intake, exercise
      guidelines for healthy adults, general stress management guidelines, and
      healthful eating for older adults. Twenty-four of the 26 topics had mean levels
      of need greater than or equal to moderate need (mean score > or = 3). Topics with
      moderate need included guidelines for overweight children and adolescents,
      nutrition for chronic disease prevention, and healthful eating for various stages
      of the life cycle. The combined mean score for topics dealing with weight control
      and exercise for adults, adolescents, and children was greater than the score for
      high need (mean score > 4). Eighty-three percent of respondents preferred 1-page,
      printed handouts. Forty-five percent requested materials in Spanish.
      APPLICATIONS: Dietitians who work in a variety of settings can use techniques
      similar to those described here to determine the patient education materials
      practitioners need for the populations they serve. The information obtained from
      this study will be used to develop 1-page, printed handouts. A registered
      dietitian and a food and nutrition specialist with NCCES will develop and pilot
      test the handouts. These materials will be made available to primary care
      providers in North Carolina via local NCCES family and consumer education agents,
      many of whom are registered dietitians.

PMID- 10207401
TI  - Creating a clinical nutrition registry: prospects, problems, and preliminary
      results.
AB  - There is a tremendous gap in the information available to support the practice of
      hospital-based dietitians and to address the issue of how the risk of developing
      protein-energy malnutrition can be avoided in the majority of patients. This
      article describes the rationale and benefits of creating a nutrition registry of
      within-hospital clinical nutrition care. A nutrition registry is made up of
      observational data, collected on an ongoing basis, of nutritional interventions
      provided to hospitalized patients. It is the first step in data gathering to
      demonstrate the effectiveness of clinical nutrition interventions. The methods
      and preliminary results of a nutrition registry that was established at The
      University of Illinois Medical Center, Chicago, III, are presented. Using
      subjective global assessment, 55% (257 of 467) of patients at admission and 60%
      (280 of 467) of patients at discharge were moderately or severely malnourished.
      Patients that were normal nourished at admission and became moderately or
      severely malnourished had higher hospital charges ($40,329 for moderately
      malnourished patients, $76,598 for severely malnourished patients) than those
      that remained normal nourished ($28,368). This pattern held independent of
      admission nutritional status. Major challenges in implementation of a registry
      into the responsibilities of the staff dietitian are reviewed. The conclusion of
      this study is that nutrition registries can be established and will provide the
      much needed baseline data to document the impact of nutrition interventions on
      outcomes of medical care.

PMID- 10207402
TI  - Cognitive and demographic correlates of low-fat vending snack choices among
      adolescents and adults.

PMID- 10207403
TI  - Attitudes about health and nutrition are more indicative of dietary quality in 50
      to 75-year-old women than weight and appearance concerns.

PMID- 10207404
TI  - A liberalized geriatric diet fits most dietary prescriptions for long-term-care
      residents.

PMID- 10207405
TI  - Overview of lactose maldigestion (lactase nonpersistence).

PMID- 10207406
TI  - The primary care physician's view of managed care in 1998.

PMID- 10207407
TI  - Pulmonary MR angiography: is it ready now?

PMID- 10207408
TI  - Pulmonary tuberculosis: the essentials.

PMID- 10207409
TI  - The CT angiogram sign.

PMID- 10207410
TI  - Lung transplantation for lymphangioleiomyomatosis: role of imaging in the
      assessment of complications related to the underlying disease.
AB  - PURPOSE: To identify the complications and imaging findings related to
      lymphangioleiomyomatosis (LAM) after lung transplantation. MATERIALS AND METHODS:
      The authors retrospectively reviewed the clinical histories and imaging studies
      of 13 patients from five major medical centers who underwent unilateral (n = 8)
      or bilateral (n = 5) lung transplantation for LAM between 1991 and 1997.
      Complications related to LAM, both before and after transplantation, were
      recorded. RESULTS: The following LAM-related complications were found during and
      after transplantation: excessive pleural adhesions (n = 4), native lung
      pneumothorax (n = 3), chylous effusion (n = 1), chylous ascites (n = 3),
      complications from renal angiomyolipomas (n = 4), and recurrent LAM (n = 1).
      Diagnosis could be made or suggested with computed tomography (CT) in all cases.
      Four patients (31%) died; one patient died of complications of LAM. CONCLUSIONS:
      Patients who have undergone lung transplantation for LAM have increased morbidity
      and mortality due to complications related to their underlying disease. These LAM
      related complications can be diagnosed or suggested with CT.

PMID- 10207411
TI  - Interstitial lung disease in association with polymyositis-dermatomyositis: long
      term follow-up CT evaluation in seven patients.
AB  - PURPOSE: To determine the long-term follow-up computed tomographic (CT) findings
      of interstitial lung disease associated with polymyositis-dermatomyositis.
      MATERIALS AND METHODS: CT scans in seven patients with interstitial lung disease
      and associated polymyositis-dermatomyositis were evaluated retrospectively. Six
      patients underwent sequential CT (follow-up range, 2-8 years; mean, 4.3 years).
      Histologic confirmation of pulmonary involvement was available in five patients.
      RESULTS: The predominant finding on the initial CT scans in four patients was
      subpleural consolidation, which corresponded to bronchiolitis obliterans
      organizing pneumonia with or without coexistent chronic eosinophilic pneumonia.
      In most cases, consolidation improved with use of corticosteroid and/or
      immunosuppressive therapy; in two patients, however, consolidation evolved into
      honeycombing. In one patient, diffuse areas of ground-glass opacity and
      consolidation appeared rapidly during illness; this patient died of sudden, rapid
      deterioration. In one patient with subpleural linear opacities, parenchymal
      abnormalities slowly progressed, and linear opacities had evolved into
      honeycombing at 8-year follow-up. In one patient with histologically proved
      organizing diffuse alveolar damage, bilateral patchy areas of ground-glass
      opacity and consolidation were seen. In one patient, subpleural bands changed to
      subpleural lines on sequential CT scans. CONCLUSION: CT provides an excellent
      demonstration of the lung changes in patients with interstitial lung disease and
      associated polymyositis-dermatomyositis.

PMID- 10207412
TI  - Q fever pneumonia: appearance on chest radiographs.
AB  - PURPOSE: To determine the radiographic features of Q fever pneumonia. MATERIALS
      AND METHODS: Chest radiographs in 85 patients admitted to the hospital during a 7
      year period with Q fever pneumonia were retrospectively reviewed by two
      observers. RESULTS: The most commonly recorded abnormalities were segmental (n =
      53 [62%]) and lobar (n = 15 [18%]) areas of opacity. Segmental pneumonia was
      observed as a unilateral single area of opacity in 38 (72%) patients. It was more
      frequently located in the upper lobes. The left upper lobe was involved in 31% of
      patients, the right upper lobe, in 23%; and the right lower lobe, in 27%. Lobar
      pneumonia was less frequently observed as a single lesion in eight (53%) of 15
      patients; It was located in the left upper lobe in 31% and in the right middle
      lobe in 27% of patients. There was no correlation between the extent of pulmonary
      involvement and the course of the disease; the outcome was favorable in all
      patients. Complete resolution of the radiographic findings occurred in a mean of
      39 days. CONCLUSION: The radiographic differentiation of Q fever pneumonia from
      the other community-acquired pneumonias is not possible. Clinical, serologic, and
      epidemiologic data provide the best basis for diagnosis.

PMID- 10207413
TI  - Mammography in the 1990s: the United States and Canada.
AB  - PURPOSE: To evaluate trends in mammography quality before and after the
      implementation of the Mammography Quality Standards Act (MQSA) of 1992 and to
      compare technical data collected in the United States with corresponding data
      obtained from the first survey of mammography facilities conducted in 1994-1995
      in Canada. MATERIALS AND METHODS: Data from MQSA inspections conducted in 1995
      1997 were analyzed and compared with survey data on U.S. mammography facilities
      acquired before the MQSA. Technical indicators of mammography quality such as
      radiation dose phantom image score, film processing, and darkroom fog were
      analyzed. RESULTS: In the United States, phantom image scores, along with other
      technical measures of performance such as film processing, darkroom fog, and x
      ray beam quality, have improved continuously since 1985. The U.S. mean glandular
      dose has increased to 1.6 mGy compared with the Canadian dose of 1.1 mGy. The
      mean total phantom image score with artifact subtraction was 11.1 in Canada in
      1994-1995 and 11.8 in the U.S. in 1997. CONCLUSION: Mammography quality is better
      today than it has been at any other time in the United States. With the exception
      of radiation dose. Canadian technical measures of performance are comparable to
      measures before MQSA in the United States.

PMID- 10207414
TI  - Acute pulmonary embolism: diagnosis with MR angiography.
AB  - PURPOSE: To prospectively evaluate pulmonary magnetic (MR) angiography as a
      diagnostic examination for acute pulmonary embolism (PE). MATERIALS AND METHODS:
      Thirty-six consecutive patients (19 women, 17 men; age range, 28-84 years)
      underwent pulmonary digital subtraction angiography (DSA) and pulmonary MR
      angiography. MR angiograms were obtained during suspended respiration and the
      pulmonary arterial phase of gadolinium-based contrast medium injection. A steady
      state gradient-recalled-echo sequence with free induction decay sampling was
      used. DSA studies were interpreted for the presence of acute PE by two
      independent radiologists; an adjudicator made the final decision on discordant
      interpretations. RESULTS: By using DSA, a total of 19 acute pulmonary emboli were
      depicted in 13 patients. Prospectively, 13 of these emboli were depicted by using
      MR angiography. MR angiography missed six emboli: Four required the DSA
      adjudicator to make the decision, and one was in a patient whose MR angiogram was
      acquired during breathing. Four of these six emboli were small subsegmental
      emboli, and two were segmental. CONCLUSION: Performed without pulmonary arterial
      catheterization, iodinated contrast media, or ionizing radiation, pulmonary MR
      angiography had a high accuracy for depicting lobar and segmental emboli, but was
      unable to depict four of five subsegmental emboli.

PMID- 10207415
TI  - Abdominal aortic aneurysm in high-risk patients: short- to intermediate-term
      results of endovascular repair.
AB  - PURPOSE: To assess the safety and efficacy of endovascular repair of abdominal
      aortic aneurysm in high-risk patients during the short to intermediate term.
      MATERIALS AND METHODS: Endovascular aneurysm repair was performed in 50 patients
      considered too high risk for conventional repair. Stent-grafts were inserted
      through surgically exposed femoral arteries with fluoroscopic guidance. The
      anesthetic technique was epidural in 36 patients, general in 12, and local in
      two. Aortouniiliac stent-grafts were inserted in 42 patients and aortoaortic in
      eight. RESULTS: There were no deaths and no conversions to open surgical repair.
      The primary success rate (complete aneurysm exclusion according to CT criteria)
      was 88% (44 of 50). The secondary, clinical, and continuing success rates were
      all 98% (49 of 50). Surgical time was 196 minutes +/- 67 (mean +/- SD), blood
      loss was 284 mL +/- 386, and volume of contrast material administered was 153 mL
      +/- 64. The time from the end of the surgery to resumption of a normal diet was
      0.58 days +/- 0.56, to ambulation was 1.22 days +/- 0.77, and to discharge from
      the hospital was 3.63 days +/- 1.60. Wound problems accounted for the majority of
      complications. There were no instances of pulmonary failure, renal failure, stent
      graft migration, or late leakage. CONCLUSION: Endovascular repair of abdominal
      aortic aneurysm is feasible in two-thirds of high-risk patients, with a low
      mortality and high success rate during the short to intermediate term.

PMID- 10207416
TI  - Renal artery stenosis: evaluation with conventional angiography versus gadolinium
      enhanced MR angiography.
AB  - PURPOSE: To evaluate the interobserver and intermodality variability of
      conventional angiography and gadolinium-enhanced magnetic resonance (MR)
      angiography in the assessment of renal artery stenosis. MATERIALS AND METHODS:
      Fifty-four patients underwent conventional angiography and gadolinium-enhanced
      three-dimensional gradient-echo MR angiography. Three angiographers blinded to
      each other's interpretations and the MR angiographic findings assessed the
      conventional angiograms for renal artery stenosis. Similarly, three blinded MR
      imagers evaluated the MR angiograms. RESULTS: Interobserver variability for the
      degree of renal artery stenosis in the 107 kidneys evaluated was not
      significantly different between the two modalities. The mean SD of the degree of
      stenosis was 6.9% at MR angiography versus 7.5% at conventional angiography
      (alpha < or = .05, P > .05). In 70 kidneys (65%), the average degree of stenosis
      reported by the readers for the two modalities differed by 10% or less. In 22
      cases (21%), the degree of stenosis was overestimated with MR angiography by more
      than 10% relative to the results of conventional angiography. In 15 cases (14%),
      the degree of stenosis was underestimated with MR angiography by more than 10%.
      CONCLUSION: Gadolinium-enhanced MR angiography permits evaluation of renal artery
      stenosis with an interobserver variability comparable with that of conventional
      angiography.

PMID- 10207417
TI  - Coagulative interstitial laser-induced thermotherapy of benign prostatic
      hyperplasia: online imaging with a T2-weighted fast spin-echo MR sequence-
      experience in six patients.
AB  - PURPOSE: To determine if hypointense lesions clearly outline on T2-weighted fast
      spin-echo (SE) magnetic resonance (MR) images obtained during coagulative
      interstitial laser-induced thermotherapy (LITT) of a prostate with benign
      hyperplasia. MATERIALS AND METHODS: In six patients with benign prostatic
      hyperplasia (BPH), 12 LITT treatments were followed online with repetitive axial
      T2-weighted fast SE imaging (repetition time, 3,700 msec; echo time, 138 msec;
      acquisition time, 19 seconds). Development, time course, correlation with
      interstitial tissue temperature, and diameters of hypointense lesions around the
      laser diffusor tip were investigated. Lesion diameters on T2-weighted images
      acquired during LITT were compared with diameters of final lesions on T2-weighted
      images and unperfused lesions on enhanced T1-weighted SE images obtained at the
      end of therapy. RESULTS: Hypointense lesions developed within 20-40 seconds of
      LITT. Average correlation coefficients between interstitial temperature
      development and signal intensity development were 0.92 during LITT and 0.90 after
      LITT. Regression slopes were significantly steeper during LITT (0.67% signal
      intensity change per degree Celsius) than after LITT (0.47% per degree Celsius; P
      = .038). Lesions remained visible after LITT for all procedures. Average maximum
      diameters of lesions were 1-3 mm larger during LITT than after LITT (P = .0006
      .019). CONCLUSION: Repetitive T2-weighted fast SE MR imaging during interstitial
      coagulative LITT of BPH demonstrates the development of permanent hypointense
      prostate lesions. However, posttherapeutic lesion diameters tend to be
      overestimated during LITT.

PMID- 10207418
TI  - Cerebral and renal embolization after lymphography in a patient with non-Hodgkin
      lymphoma: case report.
AB  - An unusual case of lipid embolization to brain and kidney after lymphography in a
      patient with non-Hodgkin lymphoma of the upper anterior mediastinum is reported.
      Contrast material-enhanced echocardiography demonstrated a right-to-left shunt to
      the left atrium without evidence of a patent foramen ovale. Echo contrast
      particles were transiently present within the tumor surrounding the great
      vessels.

PMID- 10207419
TI  - Large degenerated adrenal adenomas: radiologic-pathologic correlation.
AB  - PURPOSE: To correlate the radiologic and pathologic findings and differential
      diagnosis of large, degenerated adrenal adenomas. MATERIALS AND METHODS: The
      authors reviewed the radiologic and pathologic characteristics of 30 large
      adenomas with cystic regions or areas of heterogeneity that were either intrinsic
      or demonstrated at contrast material-enhanced computed tomography (CT) or
      magnetic resonance (MR) imaging. Images of 24 adrenocortical carcinomas were also
      reviewed to determine whether differentiating characteristics existed. RESULTS:
      Most of the adrenocortical adenomas were in asymptomatic women. Ten adenomas
      contained calcification. Pathologic examination revealed good correlation between
      heterogeneity and liquefied regions. Histologic examination confirmed regions of
      adenomatous tissue with areas of hemorrhage, amorphous degenerated material,
      calcification, and fibrosis. Some tumors contained myelolipomatous foci. Although
      some clinical and imaging findings differed between the groups, no features could
      be found that enabled the radiologic differentiation of adenomas from carcinomas.
      CONCLUSION: A subgroup of adrenal adenomas are larger, more heterogeneous, and
      more frequently calcified than those with the usual imaging findings. Central
      necrosis, hemorrhage, or both are responsible for many of the imaging features.
      Differentiation of these lesions from other large adrenal masses, including
      adrenal carcinoma, cannot be made by means of imaging alone; resection is
      required for the definitive diagnosis.

PMID- 10207420
TI  - Prediction of benign and malignant endometrial disease: hysterosonographic
      pathologic correlation.
AB  - PURPOSE: To determine the transvaginal hysterosonographic appearances of benign
      and malignant endometrial disease. MATERIALS AND METHODS: From April 11, 1994,
      through August 1, 1996, a total of 88 women (age range, 25-81 years) underwent
      transvaginal hysterosonography and histopathologic evaluation of the endometrium
      after dilation and curettage or after hysterectomy. A benign appearance at
      transvaginal hysterosonography was defined as a thin endometrium, diffuse smooth
      endometrial thickening, or a smoothly marginated, homogeneously echogenic,
      pedunculated endoluminal mass. A suspicious appearance was defined as either
      irregular thickening of the endometrium or an inhomogeneous endoluminal mass.
      RESULTS: Of 88 women, 37 had a benign-appearing endometrium at transvaginal
      hysterosonography; at histologic examination, 16 had a proliferative endometrium,
      12 had a secretory endometrium, six had polyps, two had an inactive endometrium,
      and one had carcinoma. Of the 51 women with suspicious endometrial appearances,
      eight had carcinoma, 24 had adenomatous polyps, five had hyperplasia, 11 had
      fibroids, and three had endometritis. For carcinoma, the sensitivity of
      transvaginal hysterosonography was 89%, specificity was 46%, positive predictive
      value was 16%, and negative predictive value was 97%. CONCLUSION: A thin
      endometrium or diffuse smooth endometrial thickening is predictive of benign
      endometrial histologic findings, but all women with endoluminal masses require
      further histologic evaluation to exclude malignant disease.

PMID- 10207421
TI  - Predicting ovarian malignancy: application of artificial neural networks to
      transvaginal and color Doppler flow US.
AB  - PURPOSE: To compare the performance of artificial neural networks (ANNs) with
      that of multiple logistic regression (MLR) models for predicting ovarian
      malignancy in patients with adnexal masses by using transvaginal B-mode and color
      Doppler flow ultrasonography (US). MATERIALS AND METHODS: A total of 226 adnexal
      masses were examined before surgery: Fifty-one were malignant and 175 were
      benign. The data were divided into training and testing subsets by using a "leave
      n out method." The training subsets were used to compute the optimum MLR
      equations and to train the ANNs. The cross-validation subsets were used to
      estimate the performance of each of the two models in predicting ovarian
      malignancy. RESULTS: At testing, three-layer back-propagation networks, based on
      the same input variables selected by using MLR (i.e., women's ages, papillary
      projections, random echogenicity, peak systolic velocity, and resistance index),
      had a significantly higher sensitivity than did MLR (96% vs 84%; McNemar test, p
      = .04). The Brier scores for ANNs were significantly lower than those calculated
      for MLR (Student t test for paired samples, P = .004). CONCLUSION: ANNs might
      have potential for categorizing adnexal masses as either malignant or benign on
      the basis of multiple variables related to demographic and US features.

PMID- 10207422
TI  - Intravascular gas as an incidental finding at US after blunt abdominal trauma.
AB  - PURPOSE: To describe the occurrence and importance of intravascular gas at
      ultrasonography (US) during the initial examination of patients after blunt
      abdominal trauma. MATERIALS AND METHODS: Reports of all abdominal US examinations
      performed at one institution for blunt trauma from October 1995 through June 1996
      were reviewed. The charts of patients with intravascular gas were examined to
      determine the mechanism of injury, associated findings, and clinical outcome.
      RESULTS: A total of 730 patients underwent abdominal US examinations during the 9
      months of study; five had intravascular gas demonstrated. Two patients had portal
      venous gas, one had hepatic venous gas, and two had inferior vena caval gas. Four
      of the five patients were involved in motor vehicle accidents, and one had been
      assaulted. In patients in whom follow-up studies were obtained, there was no
      evidence of intravascular gas at US or computed tomography. No cause was found at
      imaging or clinical examination. CONCLUSION: Intravascular gas may occur as a
      transient incidental finding after blunt abdominal trauma.

PMID- 10207423
TI  - Improved imaging of liver metastases with stimulated acoustic emission in the
      late phase of enhancement with the US contrast agent SH U 508A: early experience.
AB  - PURPOSE: To see whether stimulated acoustic emission (SAE) in the liver
      parenchyma in the late phase of enhancement with SH U 508A increases the
      conspicuity of occult metastases at ultrasonography (US). MATERIALS AND METHODS:
      Eighteen patients with known hypo- or hypervascular hepatic metastases underwent
      US after SH U 508A administration, after a delay of at least 5 minutes, to ensure
      decay of blood pool enhancement. In 16 patients with visible metastases,
      conspicuity was compared on registered SAE and gray-scale scans by two blinded
      readers and by using computerized analysis of relative gray-scale and color
      Doppler conspicuity scores inside and outside the lesion. In nine patients, areas
      suspected of being involved but without definite gray-scale masses were imaged in
      the same way. Paired sections were analyzed by two blinded readers looking for
      parenchymal color defects without corresponding gray-scale masses; nine control
      images from three healthy volunteers were also included. RESULTS: Intense,
      transient parenchymal SAE was seen in all subjects. All metastases appeared as
      areas of reduced or absent signal. The conspicuity score was 80% for SAE versus
      9% for gray-scale US (P < .001, Wilcoxon signed rank test). SAE-specific defects
      were seen in all patients but in none of the volunteers. Metastases seen on SAE
      but undetectable on gray-scale images were proved in three patients. CONCLUSION:
      SAE with SH U 508A improves the conspicuity of metastases. SAE-specific defects
      may reveal isoechoic or subtle metastases.

PMID- 10207424
TI  - Diagnosis please. Case 7: Hydranencephaly.

PMID- 10207425
TI  - Occlusive colon carcinoma: virtual colonoscopy in the preoperative evaluation of
      the proximal colon.
AB  - PURPOSE: To evaluate the use of preoperative virtual colonoscopy to examine the
      proximal colon in patients with distal occlusive carcinomas, defined as cancers
      that cannot be traversed endoscopically. MATERIALS AND METHODS: Twenty-nine
      patients with occlusive colorectal carcinomas underwent preoperative virtual
      colonoscopy with use of a standard protocol. Patients with acute bowel
      obstruction were excluded. Results of virtual colonoscopy were compared with the
      findings of preoperative colonoscopy, preoperative barium enema examination,
      intraoperative colon palpation, histopathologic outcome, and postoperative
      colonoscopy and barium enema examination, where possible. RESULTS: Virtual
      colonoscopy helped identify all 29 occlusive carcinomas and demonstrated two
      cancers and 24 polyps in the proximal colon. Both synchronous cancers were
      confirmed intraoperatively and resected. Postoperative conventional colonoscopy
      in 12 patients confirmed 16 polyps identified at virtual colonoscopy and
      demonstrated two subcentimeter polyps missed at virtual colonoscopy.
      Postoperative barium enema examination was performed in two patients and helped
      confirm two polyps identified at virtual colonoscopy. Virtual colonoscopy
      successfully demonstrated the proximal colon in 26 of 29 patients examined
      compared with preoperative barium enema examination, which failed to adequately
      demonstrate the proximal colon in any patient examined. CONCLUSION: Virtual
      colonoscopy is a feasible and useful method for evaluating the entire colon
      before surgery in patients with occlusive carcinomas.

PMID- 10207427
TI  - Acute pancreatic transplant rejection: evaluation with dynamic contrast-enhanced
      MR imaging compared with histopathologic analysis.
AB  - PURPOSE: To evaluate the use of dynamic contrast material-enhanced gradient
      recalled-echo MR imaging for the diagnosis of acute pancreatic transplant
      rejection, as confirmed at histopathologic analysis. MATERIALS AND METHODS:
      Thirty MR imaging studies were performed in 25 patients within 3 days of
      percutaneous biopsy or pancreatectomy. The mean percentage of parenchymal
      enhancement (MPPE) at dynamic contrast-enhanced MR imaging was calculated.
      RESULTS: Biopsy findings were no evidence of rejection (n = 7 [23%]), mild
      rejection (n = 10 [33%]), moderate (n = 6 [20%]) and severe (n = 2 [7%]) acute
      rejection, and infarction (n = 5 [17%]). The corresponding MPPEs at 1 minute were
      106%, 66%, 62%, 57%, and 3%, respectively. Overlap of cases in the normal and
      rejection groups occurred; however, using an MPPE cutoff of 100% resulted in a
      sensitivity of 96%. An MPPE over 120% was seen in the normal group only. The MPPE
      was significantly greater in the normal group than in the rejection or infarction
      group (P < .05). CONCLUSION: Dynamic contrast-enhanced MR imaging is highly
      sensitive for the detection of acute pancreatic transplant rejection. Because of
      overlap of cases in the normal and rejection groups, percutaneous biopsy may be
      needed in some cases. Pancreatic allografts with infarction can be clearly
      identified.

PMID- 10207428
TI  - Hepatic nodules in Budd-Chiari syndrome: imaging features.
AB  - PURPOSE: To analyze the imaging features of nodules associated with Budd-Chiari
      syndrome. MATERIALS AND METHODS: The authors retrospectively studied images
      obtained in 23 patients with liver nodules who were being followed up for Budd
      Chiari syndrome. Doppler ultrasonography was performed in all patients, computed
      tomography in 16, and magnetic resonance (MR) imaging in 20. The following lesion
      features were evaluated: location, number, size, vascularization, qualitative
      signal intensity at MR imaging, and homogeneity. Nodules were diagnosed on the
      basis of histopathologic findings or clinical and biologic data with no change at
      imaging during 2-year follow-up. RESULTS: All patients had histopathologic
      features of chronic Budd-Chiari syndrome. Four patients had hepatocellular
      carcinoma (HCC), with one to three lesions. The mean diameter of the largest HCC
      lesion in each patient was 7.3 cm. All HCC lesions were heterogeneous and had
      high signal intensity on T2-weighted MR images. Nineteen patients had multiple
      benign regenerative nodules, most of which were smaller than 4 cm. Most nodules
      were homogeneous and hyperintense on T1- and T2-weighted images. In 15 patients,
      nodules were hypervascular in the arterial phase. CONCLUSION: In patients with
      chronic Budd-Chiari syndrome, multiple (> 10) small (< 4-cm) lesions are
      suggestive of benignity.

PMID- 10207426
TI  - Diverticulitis versus colon cancer: differentiation with helical CT findings.
AB  - PURPOSE: To retrospectively determine the computed tomographic (CT) signs
      associated with diverticulitis or colon cancer, and to prospectively apply these
      signs in the differentiation of these diseases. MATERIALS AND METHODS: Fifty
      eight CT scans in cases of proved diverticulitis (n = 27) or colon cancer (n =
      31) were evaluated retrospectively by radiologists (blinded to the proved
      diagnosis) for the presence or absence of previously reported CT findings. These
      findings were correlated with the pathologic or final clinical diagnosis. The
      retrospective findings were applied in a prospective evaluation with a new set of
      72 CT scans. The same five radiologists rendered a diagnosis according to a five
      point confidence scale from definitely benign to definitely malignant. Individual
      and consensus readings were correlated with the final diagnosis. RESULTS:
      Retrospectively, pericolonic inflammation (P < .01) and segment involvement
      greater than 10 cm (P < .012) were the most significant findings for
      diverticulitis; pericolonic lymph nodes (P < .0001) and luminal mass (P < .003)
      were the most significant findings for colon cancer. Prospectively, an
      unequivocal diagnosis was made correctly in 16 (40%) of 40 cases of
      diverticulitis and 21 (66%) of 32 cases of colon cancer. CONCLUSION: When there
      are no pericolonic lymph nodes adjacent to a segment of colonic wall thickening,
      with pericolonic inflammatory changes, the most likely diagnosis is
      diverticulitis. When pericolonic lymph nodes are present, with or without
      pericolonic edema, the most likely diagnosis is colon cancer.

PMID- 10207429
TI  - Regenerative nodules in liver cirrhosis: findings at CT during arterial
      portography and CT hepatic arteriography with histopathologic correlation.
AB  - PURPOSE: To determine the appearance of regenerative nodules in patients with
      liver cirrhosis at computed tomography (CT) during arterial portography (CTAP)
      and CT hepatic arteriography (CTHA). MATERIALS AND METHODS: CTAP and CTHA of the
      liver were performed in 28 consecutive patients with hepatocellular carcinoma
      (HCC) who were scheduled to undergo partial resection of the liver. Helical CTAP
      was performed after contrast material injection into the superior mesenteric
      artery followed by helical CTHA after contrast material injection into the
      hepatic artery. CT scans were analyzed for the presence of identifiable nodules
      and their size; results were correlated with gross and microscopic findings.
      RESULTS: Resected livers showed cirrhosis in 20 patients, chronic hepatitis in
      four, and normal liver in four. Among the 20 patients with cirrhosis,
      regenerative nodules were demonstrated as enhancing 3-10 mm nodules surrounded by
      lower attenuation fibrous septa 0.8-1.5 mm thick at CTAP in seven patients and
      nonenhancing nodules of the same size surrounded by enhancing fibrous septa at
      CTHA in 15 patients. The degree of fibrosis determined the conspicuity of
      nodules. CONCLUSION: Regenerative nodules in cirrhotic liver are visualized as
      enhancing nodules surrounded by lower attenuation thin septa at CTAP and
      nonenhancing nodules surrounded by enhancing fibrous septa at CTHA. CTHA is more
      sensitive than CTAP in depicting regenerative nodules (P < .005).

PMID- 10207430
TI  - Hepatic lesion detection: comparison of MR imaging after the administration of
      superparamagnetic iron oxide with dual-phase CT by using alternative-free
      response receiver operating characteristic analysis.
AB  - PURPOSE: To compare the performance of magnetic resonance (MR) imaging after the
      administration of superparamagnetic iron oxide (SPIO) and dual-phase computed
      tomography (CT) in the depiction of liver metastases. MATERIALS AND METHODS:
      Fifty-one hepatic resection candidates with known colorectal metastases were
      examined. MR imaging comprised fast spin-echo (SE) T2-weighted imaging, T1
      weighted gradient-echo (GRE) fast low-angle shot imaging before SPIO enhancement,
      dual-echo SE imaging, T2-weighted fast low-angle shot imaging, and T1-weighted
      GRE imaging after SPIO enhancement. CT was performed with 8-mm collimation and
      1:1 pitch; imaging commenced 20 seconds and 65-70 seconds after injection of 150
      mL of contrast medium. All images were reviewed independently by four blinded
      observers. The alternative-free response receiver operating characteristic (ROC)
      method was used to analyze the results, which were correlated with findings from
      surgery, intraoperative ultrasonography, and histopathologic studies in 31
      patients and with consensus review together with all other imaging and clinical
      follow-up in 20 patients. Sensitivities were also calculated. RESULTS: The mean
      sensitivity of MR was significantly higher than that of CT (p < .02): 79.8% for
      MR and 75.3% for CT for all lesions, and 80.6% for MR and 73.5% for CT for
      malignant lesions. The mean areas under the alternative-free response ROC curves
      were 0.83 for MR and 0.78 for CT (difference not significant). CONCLUSION: SPIO
      enhanced MR imaging was more sensitive than dual-phase CT in the depiction of
      colorectal metastases.

PMID- 10207431
TI  - Embolization of portal vein branches induces hepatocyte replication in swine: a
      potential step in hepatic gene therapy.
AB  - PURPOSE: To determine whether embolization of portal vein branches would
      stimulate hepatocyte replication in pigs. MATERIALS AND METHODS: The portal vein
      branches supplying 50%-70% of the liver were embolized in eight pigs by using a
      combination of coils and polyvinyl alcohol particles. The extent of embolization
      was assessed at portography in all animals and at computed tomography in one
      animal. Hepatocyte replication was determined by calculating the percentage of
      cells that incorporated bromodeoxyuridine into their nuclei. Animals survived up
      to 35 days after the procedure. RESULTS: Embolization of the portal vein branches
      supplying the left and median lobes caused transient increases of less than 70%
      in portal vein pressures and of less than 100% in liver enzyme levels.
      Indocyanine green clearance was measured in two animals and decreased less than
      50%. The percentage of replicating hepatocytes in the nonembolized lobe was 0% on
      day 0, 7% on day 2, 14% on day 7, and 2% on day 12. CONCLUSION: Substantial
      hepatocyte replication occurred 2-7 days after embolization of portal vein
      branches. Further research will help determine if this procedure can facilitate
      retroviral transduction in large animals. If successful, the low morbidity of
      this method may allow its use in humans for gene therapy.

PMID- 10207432
TI  - Electron-beam therapy for AIDS-related molluscum contagiosum lesions: preliminary
      experience.
AB  - PURPOSE: To determine the effects of electron-beam therapy on cutaneous molluscum
      contagiosum lesions in patients with acquired immunodeficiency syndrome (AIDS),
      because current treatment modalities are limited in their effectiveness and by
      long-term rates of lesion recurrence. MATERIALS AND METHODS: Five patients with
      AIDS, with 23 molluscum contagiosum lesion sites, received electron-beam
      radiation treatment of recurrent molluscum contagiosum lesions. RESULTS: All 23
      lesions treated resolved completely and have not recurred during up to 24 months
      of follow-up. Radiation therapy was well tolerated; mild skin erythema was the
      only reported side effect. CONCLUSION: The use of electron-beam radiation is a
      promising alternative to current treatment modalities.

PMID- 10207433
TI  - Stages I-III follicular lymphoma: role of CT of the abdomen and pelvis in follow
      up studies.
AB  - PURPOSE: To evaluate the efficiency of axial computed tomography (CT) in
      detecting relapses of stage I, II, or III follicular lymphoma. MATERIALS AND
      METHODS: A total of 328 patients with previously untreated stage I, II, or III
      follicular lymphoma were treated between 1978 and 1994. Two hundred fifty-seven
      patients achieved complete response; 78 who relapsed form the basis of this
      study. Fifteen patients had stage I; 28, stage II; and 35, stage III disease.
      Fifteen patients underwent radiation therapy; 12, chemotherapy; and 51, radiation
      and chemotherapy. Medical records were reviewed to analyze the yield of abdominal
      and pelvic CT in detecting recurrence relative to the yield of standard clinical,
      hematologic, and imaging studies. A positive study was defined as one that led to
      or was abnormal at the diagnosis of recurrence. RESULTS: The median follow-up was
      101 months. Eleven relapses were detected only at abdominal, pelvic, or both
      abdominal and pelvic CT. CONCLUSION: Fourteen percent (11 of 78) of the relapses
      were detected solely at abdominal and/or pelvic CT. Eleven (4.3%) of the 257
      patients who achieved complete response benefited from abdominal and pelvic CT.
      The yield of the routine use of abdominal and pelvic CT in follow-up studies
      appears to be low for stages I-III follicular lymphoma.

PMID- 10207434
TI  - Hodgkin disease: prediction of outcome with 67Ga scintigraphy after one cycle of
      chemotherapy.
AB  - PURPOSE: To investigate gallium 67 scintigraphy performed early during treatment
      as a means to predict outcome and thus to optimize treatment of Hodgkin disease
      (HD) in the future. MATERIALS AND METHODS: Ninety-eight patients with HD were
      examined. Thirty-one patients underwent 67Ga scintigraphy after one chemotherapy
      cycle and 83 patients after a mean 3.5 cycles (range, 2-5 cycles). Sixteen
      patients underwent 67Ga scintigraphy both after one cycle and at midtreatment.
      Patients underwent whole-body scintigraphy and single photon emission computed
      tomography of the torso. Torso computed tomography (CT) was performed after a
      mean 3.5 cycles (range, 2-6 cycles). Failure-free survival was compared between
      patients with positive and patients with negative test findings (Kaplan-Meier
      method), and the significance of the difference was calculated. The association
      of failure-free survival with various prognostic clinical factors before
      treatment was compared (log-rank test univariate analysis). RESULTS: Failure-free
      survival differed significantly (P < .002) between patients with positive and
      patients with negative 67Ga scintigrams after one chemotherapy cycle but not at
      midtreatment. Failure-free survival was not significantly different between
      patients with positive and patients with negative CT scans at midtreatment.
      Twenty-two (92%) of 24 patients with negative 67Ga scintigrams after one cycle
      and 64 (82%) of 78 patients with negative scintigrams at midtreatment remained in
      complete response. In four (57%) of seven patients with positive 67Ga scintigrams
      after one cycle, treatment failed. CONCLUSION: 67Ga scintigraphy after one cycle
      of chemotherapy is a good early predictor of outcome of HD.

PMID- 10207435
TI  - Heterogeneous splenic enhancement patterns on spiral CT images in children:
      minimizing misinterpretation.
AB  - PURPOSE: To (a) determine the appearances and timing of heterogeneous splenic
      enhancement at spiral computed tomography (CT) and (b) identify variables
      influencing heterogeneous splenic enhancement. MATERIALS AND METHODS: Sequential
      isolevel (24-mAs) CT images of the spleen obtained at 6-second intervals after
      initiation of contrast material injection in 112 children (mean age, 4.5 years)
      were reviewed. Heterogeneity characteristics assessed included type, onset,
      maximum, and resolution. Relationship to variables (injection rate, age,
      splenomegaly) was assessed with the Fisher exact test. RESULTS: Eighty-one of the
      112 patients (72%) had transient heterogeneity: archiform (45 patients), diffuse
      (25 patients), and focal (11 patients). Mean times were as follows: initial
      visualization after onset of contrast material injection, 19.2 seconds; maximum
      heterogeneity, 27.3 seconds; and resolution, 47.4 seconds. Statistically
      significant relationships were seen between frequency of heterogeneity and
      injection rate (> or = 1 mL/sec, 82%; < 1 mL/sec, 50% [P = .001]), age (> 1 year,
      76%; < or = 1 year, 46% [P = .04]), and splenomegaly (present, 20%; absent, 77%
      [P = .048]). CONCLUSION: Heterogeneous splenic contrast enhancement is common,
      has several patterns of appearance, and is predictably encountered during the 70
      seconds after the initiation of contrast material injection. Injection rate, age,
      and presence of splenic disease influence the frequency with which these
      artifacts are encountered.

PMID- 10207436
TI  - Anterior joint capsule of the normal hip and in children with transient
      synovitis: US study with anatomic and histologic correlation.
AB  - PURPOSE: To study the anatomic components of the anterior joint capsule of the
      normal hip and in children with transient synovitis. MATERIALS AND METHODS: Six
      cadaveric specimens were imaged with ultrasonography (US) with special attention
      to the anterior joint capsule. Subsequently, two specimens were analyzed
      histologically. These anatomic findings were correlated with the US findings in
      58 healthy children and 105 children with unilateral transient synovitis.
      RESULTS: The anterior joint capsule comprises an anterior and posterior layer,
      mainly composed of fibrous tissue, lined by only a minute synovial membrane. Both
      fibrous layers were identified separately at US in 98 of 116 (84%) hips of
      healthy subjects and in all hips with transient synovitis. Overall, the anterior
      layer was thicker than the posterior layer. In transient synovitis compared with
      normal hips, no significant thickening of both layers was present (P = .24 and
      .57 for the anterior and posterior layers, respectively). Normal variants include
      plicae, local thickening of the capsule, and pseudodiverticula. CONCLUSION:
      Increased thickness of the anterior joint capsule in transient synovitis is
      caused entirely by effusion. There is no US evidence for additional capsule
      swelling or synovial hypertrophy.

PMID- 10207437
TI  - Symptomatic lumbar facet joint synovial cysts: clinical assessment of facet joint
      steroid injection after 1 and 6 months and long-term follow-up in 30 patients.
AB  - PURPOSE: To study the results of facet joint intraarticular steroid injections in
      patients with symptomatic lumbar facet joint synovial cysts. MATERIALS AND
      METHODS: Data from 30 patients (age range, 44-82 years; mean age, 67 years) with
      nerve root pain due to a lumbar facet joint synovial cyst and treated with facet
      joint steroid injection were retrospectively studied. On the basis of MacNab
      criteria, the clinical course of nerve root pain was evaluated after 1 (n = 30)
      and 6 (n = 28) months. Data from long-term follow-up (mean, 26 months) were also
      available in 14 nonsurgically treated patients. RESULTS: After 1 month, the nerve
      root pain outcome was excellent or good in 20 patients (67%) and fair or poor in
      10 (33%). After 6 months, 10 (50%) of these 20 patients still had excellent or
      good results, and 18 (60%) of the 30 patients had a fair or poor clinical status,
      14 of whom underwent surgery; two patients (7%) were lost to follow-up. Excellent
      and good results were maintained at further follow-up (range, 9-50 months).
      CONCLUSION: One-third of patients with symptomatic lumbar facet joint synovial
      cysts had long-lasting acceptable benefit from facet joint steroid injections in
      this study. Steroid injection should be indicated before surgery.

PMID- 10207438
TI  - Fatty infiltration of osseous structures: a long-term complication of oleothorax-
      case report.
AB  - Thoracic imaging of a patient treated for pulmonary tuberculosis with oleothorax
      therapy before the antibiotic era demonstrated a rare complication. Gross
      invasion by lipid with subsequent pathologic fracture of the adjacent thoracic
      vertebra may give rise to symptomatic spinal cord compression. Magnetic resonance
      imaging is a useful modality for help in diagnosing treatment complications of
      oleothorax.

PMID- 10207440
TI  - Presurgical evaluation of the motor hand area with functional MR imaging in
      patients with tumors and dysplastic lesions.
AB  - PURPOSE: To test an optimized functional magnetic resonance (MR) imaging
      procedure to depict the motor hand representation area (HRA) in patients with
      epilepsy lesions near the central sulcus. MATERIALS AND METHODS: Fast low-angle
      shot MR imaging was performed with an oblique single-section imaging technique in
      eight control subjects (10 hemispheres) and six patients (12 hemispheres). Three
      series of five activation images (obtained while subjects performed repetitive
      finger-to-thumb opposition movements) and five rest images were acquired. Each
      hemisphere was studied in three adjacent sections. Difference maps (obtained with
      simple subtraction between activation and rest images) were compared with t-test
      maps. RESULTS: In control subjects, the HRA was visible in 27 of 30 sections.
      Qualitatively, activation was seen better on t-test maps in 14 and on difference
      maps in four of these sections. In all patients, motor activation could be seen
      in the hemisphere that contained the lesion. This activation was considered
      normal in four patients. In two patients, the HRA was deformed. Functional MR
      imaging activation in the motor area was confirmed with Penfield stimulation in
      five patients. CONCLUSION: Functional MR imaging findings in the preoperative
      assessment of dysplastic lesions around the central sulcus are the same as for
      tumors. t-test maps are superior to difference maps in the treatment of motor
      functional MR imaging data.

PMID- 10207439
TI  - Hyperacute stroke: simultaneous measurement of relative cerebral blood volume,
      relative cerebral blood flow, and mean tissue transit time.
AB  - PURPOSE: To investigate additional information provided by maps of relative
      cerebral blood flow in functional magnetic resonance (MR) imaging of human
      hyperacute cerebral ischemic stroke. MATERIALS AND METHODS: Diffusion-weighted
      and hemodynamic MR imaging were performed in 23 patients less than 12 hours after
      the onset of symptoms. Maps of relative cerebral blood flow and tracer mean
      tissue transit time were computed, as were maps of apparent diffusion and
      relative cerebral blood volume. Acute lesion volumes on the maps were compared
      with follow-up imaging findings. RESULTS: In 15 of 23 subjects (65%), blood flow
      maps revealed hemodynamic abnormalities not visible on blood volume maps. A
      mismatch between initial blood flow and diffusion findings predicted growth of
      infarct more often (12 of 15 subjects with infarcts that grew) than did a
      mismatch between initial blood volume and diffusion findings (eight of 15).
      However, lesion volumes on blood volume and diffusion maps correlated better with
      eventual infarct volumes (r > 0.90) than did those on blood flow and tracer mean
      transit time maps (r approximately 0.6), likely as a result of threshold effects.
      In eight patients, blood volume was elevated around the diffusion abnormality,
      suggesting a compensatory hemodynamic response. CONCLUSION: MR imaging can
      delineate areas of altered blood flow, blood volume, and water mobility in
      hyperacute human stroke. Predictive models of tissue outcome may benefit by
      including computation of both relative cerebral blood flow and blood volume.

PMID- 10207441
TI  - Progressive multifocal leukoencephalopathy and human immunodeficiency virus
      associated white matter lesions in AIDS: magnetization transfer MR imaging.
AB  - PURPOSE: To determine the magnetization transfer features of progressive
      multifocal leukoencephalopathy (PML) and human immunodeficiency virus (HIV)
      associated white matter lesions (WML) (hereafter, HIV-WML) on magnetic resonance
      (MR) images obtained in patients with acquired immunodeficiency syndrome (AIDS).
      MATERIALS AND METHODS: Conventional MR imaging and magnetization transfer MR
      imaging were performed in 21 AIDS patients with 42 areas of white matter
      hyperintensity on MR images (13 patients had 25 PML lesions, eight patients had
      17 WML). The magnetization transfer ratio was calculated for each lesion.
      RESULTS: Compared with normal-appearing white matter (magnetization transfer
      ratio = 47.9%), both PML and HIV-WML showed reduced magnetization transfer ratio.
      The magnetization transfer ratio was significantly lower in PML lesions
      (magnetization transfer ratio = 26.1%) than in HIV-WML (magnetization transfer
      ratio = 38.0%, P < .0001), and there was no overlap in the magnetization transfer
      ratio between PML lesions and HIV-WML. The separation in magnetization transfer
      ratio between the two lesion types was valid for lesion as small as 0.5 cm2.
      CONCLUSION: The larger reduction in magnetization transfer ratio for PML lesions
      is most likely due to demyelination, whereas the reduction in HIV-WML may be
      associated primarily with gliosis. PML lesions appear to cause strong reductions
      in magnetization transfer ratio early in the course of disease. Magnetization
      transfer MR imaging is a noninvasive tool that improves the differentiation
      between PML and HIV-WML in patients with AIDS.

PMID- 10207442
TI  - Dental vertical root fractures: value of CT in detection.
AB  - PURPOSE: To determine the value of computed tomography (CT) in the diagnosis of
      dental vertical root fractures relative to the value of conventional dental
      radiography. MATERIALS AND METHODS: Thirty-seven patients with 42 teeth in which
      vertical root fracture was clinically suspected underwent dental radiography and
      axial CT. Two radiologists evaluated the images independently and by consensus
      for a fracture line. The results were compared with intraoperative findings.
      RESULTS: Twenty-eight of the 42 teeth were proved intraoperatively to be
      fractured. The sensitivity and specificity averaged for the two reviewers in the
      assessment of vertical fractures were 23% and 70%, respectively, with dental
      radiography and 100% and 100%, respectively, with CT. Consensus reading showed
      sensitivities of 25% for dental radiography and 75% for CT. Eight (reviewer A) or
      nine (reviewer B) false-negative CT findings were encountered in cases in which
      metallic artifacts obscured parts of the root and in cases in which the root was
      very small in diameter. Interobserver agreement was 95% for dental radiography
      and 93% for CT. CONCLUSION: CT is superior to dental radiography in the detection
      of dental vertical root fractures.

PMID- 10207443
TI  - Cerebral gliomas and metastases: assessment with contrast-enhanced fast fluid
      attenuated inversion-recovery MR imaging.
AB  - The effect of contrast material on fast fluid-attenuated inversion-recovery
      (FLAIR) magnetic resonance images was evaluated for 16 patients with enhancing
      gliomas and 12 patients with cerebral metastases. Because of a marked T1 effect,
      fast FLAIR imaging provided a marked contrast enhancement, resulting in the
      highest tumor-to-background contrast ratio compared with standard imaging
      techniques.

PMID- 10207444
TI  - Crossed cerebellar diaschisis: assessment with dynamic susceptibility contrast MR
      imaging.
AB  - The authors investigated the feasibility of using T2-weighted, half-Fourier rapid
      acquisition with relaxation enhancement, or RARE, dynamic susceptibility contrast
      magnetic resonance (MR) imaging to depict crossed cerebellar diaschisis. In 10
      patients after unilateral supratentorial stroke, crossed cerebellar diaschisis
      was demonstrated in the relative regional cerebellar blood volume maps obtained
      with MR imaging. Cerebellar blood volume values for the nonaffected cerebellar
      hemisphere were significantly larger than those for the affected side (P =
      .0003).

PMID- 10207445
TI  - Aneurysm clips: effects of long-term and multiple exposures to a 1.5-T MR system.
AB  - The authors evaluated the ferromagnetic properties of multiple nonferromagnetic
      aneurysm clips before and after long-term and multiple exposures to a 1.5-T
      magnetic resonance system. No alterations in the magnetic properties of these
      clips was observed. These findings suggest that repeated or chronic exposure of
      patients with implanted nonferromagnetic aneurysm clips to strong static magnetic
      fields is unlikely to result in any clinically significant alteration in the
      magnetic properties of these clips.

PMID- 10207446
TI  - Coronary arteries: MR angiography with fast contrast-enhanced three-dimensional
      breath-hold imaging--initial experience.
AB  - Gadolinium-enhanced, three-dimensional, breath-hold magnetic resonance (MR)
      coronary angiography was performed in two healthy volunteers and 11 patients
      suspected or known to have coronary artery disease. MR angiograms were compared
      with those obtained with retrospective respiratory gating. Of 52 main coronary
      arteries, 47 could be visualized with the breath-hold technique and 49 with the
      gating technique. Signal-to-noise and contrast-to-noise ratios were significantly
      higher with the breath-hold technique. Overall image quality was slightly lower
      with breath-hold imaging. With either technique, three of five, significant
      coronary stenoses were correctly identified.

PMID- 10207447
TI  - Uterine arteries: bilateral catheterization with a single femoral approach and a
      single 5-F catheter--technical note.
AB  - In 197 patients, uterine embolization with a single femoral approach and a single
      5-F cobra catheter was successful in 362 of 394 (92%) uterine arteries. In six
      patients (12 arteries), distal embolization with a coaxial 3-F microcatheter was
      safer. In 10 patients with a life-threatening condition, embolization was
      performed at the anterior division of both internal iliac arteries. Bilateral
      selective embolization of the uterine arteries can be performed with a single
      catheter.

PMID- 10207448
TI  - Pulmonary embolism: diagnosis with spiral CT versus ventilation-perfusion
      scintigraphy.

PMID- 10207449
TI  - Capsule of hepatocellular carcinoma: where and how does the capsule show
      enhancement?

PMID- 10207450
TI  - Efficacy of the intradecidual sign and fallacy of the double decidual sac sign in
      the diagnosis of early intrauterine pregnancy.

PMID- 10207451
TI  - MR imaging of urinary tract infections in children.

PMID- 10207452
TI  - U.S. radiologists' workload in 1995-1996 and trends since 1991-1992.

PMID- 10207453
TI  - Liver window settings at hepatic CT: added value or marginal cost?

PMID- 10207454
TI  - Principles of digital radiography with large-area, electronically readable
      detectors: a review of the basics.

PMID- 10207455
TI  - Detecting hepatic lesions: the added utility of CT liver window settings.
AB  - PURPOSE: To prospectively evaluate the utility of adding computed tomographic
      (CT) liver windows to conventional soft-tissue windows for the detection of
      hepatic disease. MATERIALS AND METHODS: One of four radiologists experienced in
      abdominal imaging interpreted 1,175 consecutive abdominal CT scans from one
      institution. Hepatic images were first interpreted by using standard soft-tissue
      windows. The number of lesions and confidence in lesion detection were recorded.
      The liver-window images were then interpreted in conjunction with the soft-tissue
      window images, and the number of lesions and confidence in detection were
      recorded again. The proportion of patients in whom additional lesions were found
      by using liver windows was determined. RESULTS: On soft-tissue-window and liver
      window scans interpreted together, 869 (74%) patients had no hepatic lesions.
      Thirty-six (3.1%) patients had new lesions seen with the addition of liver
      windows. Twelve of these 36 patients had no lesions seen on soft-tissue-window
      scans. Twenty-six of the 36 patients with additional lesions seen had a history
      of neoplasm. There was a change in diagnosis in 1.7% of the patients with the
      addition of liver windows and a change in recommendation for follow-up in 0.85%.
      CONCLUSION: Routine interpretation of liver-window scans for all abdominal CT
      scans has limited added utility in detecting hepatic disease.

PMID- 10207456
TI  - Comparison of endoscopic retrograde cholangiopancreatography with MR
      cholangiopancreatography in patients with pancreatitis.
AB  - PURPOSE: To assess the usefulness of magnetic resonance (MR)
      cholangiopancreatography (MRCP) in the evaluation of disease in patients with
      acute or chronic pancreatitis. MATERIALS AND METHODS: MR imaging was performed at
      1.5 T in 39 patients with chronic (n = 30) or acute (n = 9) pancreatitis. The
      patients underwent a pancreas MR imaging protocol that included an MRCP sequence.
      Comparison was made with findings at endoscopic retrograde
      cholangiopancreatography (ERCP), performed within 30 days. Three blinded readers
      used a scoring system to evaluate nine segments of the pancreatic and biliary
      ducts as depicted on the ERCP and MRCP images. MRCP image quality was also
      evaluated. RESULTS: Of 196 segments analyzed, 17 were not seen at MRCP
      (sensitivity, 91%). Of the segments visualized at MRCP, 14 were incorrectly
      characterized (accuracy, 92%). At MRCP, segments not detected or mischaracterized
      were either normal, slightly dilated, or narrowed. At ERCP, 42 segments in 19
      patients were not visualized. MRCP findings were considered useful in all those
      cases. MRCP image quality was not interpretable in two cases due to artifacts.
      CONCLUSION: Very good correlation between ERCP and MRCP findings was
      demonstrated. Both modalities failed to depict pathologic conditions depicted by
      the alternative method. MRCP may obviate ERCP, particularly in patients who
      cannot undergo ERCP or in whom ERCP has been unsuccessful.

PMID- 10207457
TI  - Cystic fibrosis in adolescents and adults: fatty replacement of the pancreas--CT
      evaluation and functional correlation.
AB  - PURPOSE: To compare the computed tomographic (CT) features of pancreatic fatty
      replacement in adolescents and adults with cystic fibrosis (CF) with those in
      control subjects and to correlate the degree of fatty replacement with the
      functional status of the pancreas. MATERIALS AND METHODS: CT scans in 15 patients
      with CF (group 1) and in 15 control subjects without CF (group 2) were evaluated
      for thickness and degree of pancreatic fatty replacement. Thickness was measured
      at four anatomic levels. The pattern of pancreatic fatty replacement was visually
      evaluated in four pancreatic regions. Images were semiquantitatively analyzed by
      two readers. The degree of fatty replacement was correlated with the functional
      status of the pancreas. RESULTS: In group 1, pancreatic glandular tissue was
      significantly thinner (P < .001) and the degree of fatty replacement was
      significantly greater in the four regions (P < .001) than those in group 2. In
      Group 1, no relationship was found between the degree of pancreatic fatty
      replacement and that of pancreatic endocrine dysfunction. A significant
      relationship was found between the degree of fatty replacement and that of
      pancreatic exocrine dysfunction (P < .001). CONCLUSION: In patients with CF,
      pancreatic glandular tissue is significantly reduced in size. Pancreatic fatty
      replacement is the most frequent pattern in older patients with CF and correlates
      with pancreatic exocrine dysfunction.

PMID- 10207458
TI  - Diffusion coefficients in abdominal organs and hepatic lesions: evaluation with
      intravoxel incoherent motion echo-planar MR imaging.
AB  - PURPOSE: To determine the true diffusion coefficients of abdominal organs and
      hepatic lesions with intravoxel incoherent motion (IVIM) echo-planar magnetic
      resonance (MR) imaging. MATERIALS AND METHODS: Seventy-eight patients suspected
      of having hepatic lesions were examined with IVIM echo-planar MR imaging at 1.5
      T. There were 77 hepatic masses (27 hepatocellular carcinomas, 10 metastatic
      tumors, eight hemangiomas, and 32 cysts) in the 78 patients. The true diffusion
      coefficient D and the perfusion fraction f were calculated and compared with the
      apparent diffusion coefficient (ADC). RESULTS: Specific values of D were found
      for abdominal organs (liver, 0.72 x 10(-3) mm2/sec; spleen, 0.80 x 10(-3)
      mm2/sec; kidney, 1.38 x 10(-3) mm2/sec; gallbladder, 2.82 x 10(-3) mm2/sec) and
      for hepatic lesions (hepatocellular carcinoma, 1.02 x 10(-3) mm2/sec; metastasis,
      1.16 x 10(-3) mm2/sec; hemangioma, 1.31 x 10(-3) mm2/sec; cysts, 3.03 x 10(-3)
      mm2/sec). The ADCs of solid organs and solid lesions were significantly higher
      than their D values, indicating a high contribution of perfusion to the ADCs.
      CONCLUSION: Perfusion contributes to the ADCs of abdominal organs and hepatic
      lesions. The D and f values are useful for the characterization of hepatic
      lesions.

PMID- 10207459
TI  - Extrahepatic abdominal imaging in patients with malignancy: comparison of MR
      imaging and helical CT, with subsequent surgical correlation.
AB  - PURPOSE: To compare state-of-the-art magnetic resonance (MR) imaging with single
      phase helical computed tomography (CT) in abdominal screening for extrahepatic
      disease in patients with proved malignancy. MATERIALS AND METHODS: Fifty-seven
      patients with known malignancy underwent abdominal contrast material-enhanced
      helical CT and MR imaging from 1994 through 1997. Prospective interpretations of
      CT scans and MR images were used to assess each modality's sensitivity in
      depicting malignant extrahepatic tumor at 17 anatomic sites. Imaging findings
      were compared with surgical results in all patients. RESULTS: Helical CT depicted
      101 (66%) of 154 surgically confirmed extrahepatic tumor sites; MR imaging
      depicted 139 (90%) (P < .001). MR imaging depicted tumor in more patients at 11
      of the 17 anatomic sites; at six sites, MR imaging and helical CT were
      equivalent. MR imaging showed significantly greater depiction of extrahepatic
      tumor for the peritoneum (P < .05), bowel (P < .01), and mesentery (P < .05).
      False-negative interpretations would have altered patient care had the
      extrahepatic tumor remained undetected in 13 patients for helical CT and in six
      patients for MR imaging. CONCLUSION: State-of-the-art MR imaging can be used for
      effective abdominal screening for extrahepatic tumor in patients with malignancy.
      Compared with single-phase helical CT, MR imaging depicted more sites of
      extrahepatic tumor and was particularly advantageous for the peritoneum,
      mesentery, and bowel.

PMID- 10207460
TI  - Desmoplastic small round cell tumor of the abdomen: radiologic-histopathologic
      correlation.
AB  - PURPOSE: To characterize the imaging features of desmoplastic small round cell
      tumor of the abdomen and correlate them with the histopathologic findings.
      MATERIALS AND METHODS: Eleven of 14 patients with desmoplastic small round cell
      tumor had primary abdominal involvement. In nine of these patients (mean age, 20
      years), results of imaging studies (computed tomography in nine patients,
      ultrasonography [US] in three) and histopathologic specimens were retrospectively
      analyzed. RESULTS: The hallmark imaging feature was lobulated peritoneal masses
      (mean number, 4.4; range, 1-17) with a mean diameter of 5.0 cm (range, 2-12 cm).
      Omental and paravesical tumors were each present in six patients. Retroperitoneal
      masses were present in three patients. The tumors were well defined and
      hypoechoic at US. Heterogeneity due to tumor hemorrhage or necrosis was seen in
      seven patients. Ascites was present in five patients. Parenchymal and/or serosal
      hepatic metastases, punctate calcifications, nodular peritoneal thickening,
      lymphadenopathy, hydronephrosis, and bowel obstruction were less common
      associated findings. CONCLUSION: Bulky peritoneal soft-tissue masses without an
      apparent organ-based primary site are characteristic of intraabdominal
      desmoplastic small round cell tumor. Although the findings are nonspecific, this
      diagnosis can be considered in adolescents and young adults with characteristic
      imaging findings.

PMID- 10207461
TI  - Acute appendicitis: influence of early pain relief on the accuracy of clinical
      and US findings in the decision to operate--a randomized trial.
AB  - PURPOSE: To determine the influence of early pain relief on the diagnostic
      performance of ultrasonography (US) and on the appropriateness of the surgical
      decision. MATERIALS AND METHODS: A prospective randomized, double-blind placebo
      controlled trial with morphine was conducted. A visual analog scale was used to
      evaluate pain in 340 patients aged 16 years or older. US was performed with a
      standardized protocol. Diagnosis was confirmed at histologic analysis or, in the
      patients released without surgery, at follow-up. RESULTS: One hundred seventy
      five patients were injected with morphine, and 165 were injected with the
      placebo. Pain relief was stronger in the morphine group. In the morphine group,
      US had lower (71.1%) sensitivity (difference, -9.5%; 95% CI, -18.5%, -0.5%) and
      higher (65.2%) specificity (difference, 11.4%; 95% CI, 1.0%, 21.8%). This group
      had also a higher positive predictive value (64.6%) and a lower negative
      predictive value (71.4%), but the differences between this group and the placebo
      group were not statistically significant. Among female patients, the decision to
      operate was appropriate more often in the morphine group (75.8%), but the
      difference between this group and the placebo group was not statistically
      significant (5.1%; 95% CI, -7.4%, 17.6%). In male patients and overall, opiate
      analgesia did not influence the appropriateness of the decision. The
      appropriateness to discharge patients without surgery was 100% in all groups.
      CONCLUSION: Morphine does not improve US-based diagnosis of appendicitis.

PMID- 10207462
TI  - Radiation effective doses to patients undergoing abdominal CT examinations.
AB  - PURPOSE: To determine the radiation effective dose to adult and pediatric
      patients undergoing abdominal computed tomographic (CT) examinations. MATERIALS
      AND METHODS: Technique factors were obtained for three groups of randomly
      selected patients undergoing abdominal CT examinations: 31 children aged 10 years
      or younger; 32 young adults aged 11-18 years; and 36 adults older than 18 years.
      The radiographic techniques, together with the measured cross sections of
      patients, were used to estimate the total energy imparted to each patient. Each
      value of energy imparted was subsequently converted into the corresponding
      effective dose to the patient, taking into account the mass of the patient.
      RESULTS: All abdominal CT examinations were performed at 120 kVp with a section
      thickness of approximately 7 mm for all sizes of patients. The mean number of CT
      sections increased from 22.0 for children to 31.5 for adults, and the mean
      quantity of x radiation in milliampere-seconds increased from 220 mAs for
      children to 290 mAs for adults. The mean values (+/- SD) of energy imparted were
      72.1 mJ +/- 24.4 for children, 183.5 mJ +/- 44.8 for young adults, and 234.7 mJ
      +/- 89.4 for adults. The corresponding mean values of patient effective dose were
      6.1 mSv +/- 1.4 for children, 4.4 mSv +/- 1.0 for young adults, and 3.9 mSv +/-
      1.1 for adults. CONCLUSION: Values of energy imparted to patients undergoing
      abdominal CT examinations were a factor of three higher in adults than in
      children, but the corresponding patient effective doses were 50% higher in
      children than in adults.

PMID- 10207463
TI  - Percutaneous gastrostomy with fluoroscopic guidance: single-center experience in
      500 consecutive cancer patients.
AB  - PURPOSE: To evaluate the feasibility, complications, adequacy of feeding support,
      and tolerability of fluoroscopically guided gastrostomy in cancer patients.
      MATERIALS AND METHODS: Five hundred cancer patients were referred for
      fluoroscopically guided gastrostomy, among whom percutaneous endoscopic
      gastrostomy was contraindicated or had been unsuccessful in approximately one
      fourth. Five hundred eight fluoroscopically guided gastrostomies with T-fastener
      gastropexy were performed in 496 patients. The procedure was unsuccessful in four
      patients, and 12 patients needed a second gastrostomy. RESULTS: Fluoroscopically
      guided gastrostomy was feasible in 99% of patients. During the first 30
      postprocedure days, there were seven major complications (1.4%): cardiac failure
      (n = 1), hemorrhage (n = 1), and peritonitis (n = 5); one patient died of
      peritonitis. No major complications occurred after the 30th postprocedure day.
      There were 27 minor complications (5.4%) during the first 30 postprocedure days
      and 88 (17.6%) thereafter. Long-term minor complications mainly involved the
      disturbances and nearly always resolved once the tube was exchanged. Such
      exchanges were easily performed under fluoroscopic guidance except in two
      patients, who required repeat fluoroscopically guided gastrostomy. CONCLUSION:
      Fluoroscopically guided gastrostomy is highly feasible and safe and provides
      adequate feeding support, even when percutaneous endoscopic gastrostomy is
      impossible. Long-term complications, which are mainly tube disturbances, are
      easily treated.

PMID- 10207464
TI  - Small hepatocellular carcinoma: treatment with radio-frequency ablation versus
      ethanol injection.
AB  - PURPOSE: To compare the effectiveness of radio-frequency (RF) ablation with that
      of percutaneous ethanol injection in the treatment of small hepatocellular
      carcinoma (HCC). MATERIALS AND METHODS: Eighty-six patients with 112 small (< or
      = 3-cm-diameter) HCCs underwent RF ablation (42 patients with 52 tumors) or
      percutaneous ethanol injection (44 patients with 60 tumors). Therapeutic efficacy
      was evaluated with dual-phase spiral computed tomography performed at least 4
      months after treatment. RESULTS: Complete necrosis was achieved in 47 of 52
      tumors with RF ablation (90%) and in 48 of 60 tumors with percutaneous ethanol
      injection (80%). These results were obtained with an average of 1.2 sessions per
      tumor with RF ablation and 4.8 sessions per tumor with percutaneous ethanol
      injection. One major complication (hemothorax that required drainage) and four
      minor complications (intraperitoneal bleeding, hemobilia, pleural effusion,
      cholecystitis) occurred in patients treated with RF ablation; no complications
      occurred in patients treated with percutaneous ethanol injection. CONCLUSION: RF
      ablation results in a higher rate of complete necrosis and requires fewer
      treatment sessions than percutaneous ethanol injection. However, the complication
      rate is higher with RF ablation than with percutaneous ethanol injection. RF
      ablation is the treatment of choice for most patients with HCC.

PMID- 10207465
TI  - Renal insufficiency: usefulness of gadodiamide-enhanced renal angiography to
      supplement CO2-enhanced renal angiography for diagnosis and percutaneous
      treatment.
AB  - PURPOSE: To determine whether gadodiamide is a safe and useful angiographic
      contrast agent for help in diagnosis and percutaneous treatment of renal artery
      stenosis in patients with renal insufficiency. MATERIALS AND METHODS: Diagnostic
      renal angiography and percutaneous renal interventions were performed by using
      gadodiamide (total dose, 0.3 mmol/kg) and CO2 as intraarterial contrast agents in
      25 procedures in 24 patients with renal insufficiency. Serum creatinine levels
      were obtained within 24 hours before and at 24 and 48 hours after the procedure.
      Increases in serum creatinine of more than 44 mumol/L were considered clinically
      important. Gadodiamide-enhanced angiograms were compared with CO2-enhanced
      angiograms. RESULTS: In 23 (92%) of 25 procedures, there was no increase in serum
      creatinine level at 48 hours. One patient with acute and chronic rejection of a
      renal transplant and one with evidence of cholesterol embolization had a
      clinically important increase in serum creatinine level at 48 hours. No marked
      increase in creatinine level was observed in patients with relatively low
      baseline levels (n = 19). Gadodiamide-enhanced angiograms appeared to be better
      than CO2-enhanced angiograms for help in identifying renal artery occlusions,
      visualizing renal vessels incompletely filled with CO2, and determining the
      progress of intervention. CONCLUSION: Gadodiamide appears to be a safe and useful
      intraarterial contrast agent in patients with renal insufficiency and can be used
      to supplement or confirm CO2-enhanced angiographic findings.

PMID- 10207466
TI  - Internal carotid arterial stenosis: CT angiography with volume rendering.
AB  - PURPOSE: To determine the reliability of helical computed tomography (CT) with
      volume rendering for evaluation of internal carotid arterial stenosis. MATERIALS
      AND METHODS: In 22 patients, 44 carotid arteries were evaluated with helical CT
      and selective conventional angiography. CT data were displayed on volume-rendered
      and maximum intensity projection (MIP) images. Stenoses were measured separately
      on axial, volume-rendered, and MIP images and on conventional angiograms. Each
      artery was then graded as having no stenosis, mild (< 30%) stenosis, moderate
      (30%-70%) stenosis, severe (> 70%) stenosis, near occlusion, or occlusion.
      RESULTS: One case of stenosis was not assessable at axial CT because of an
      inappropriate scanning plane; four cases were not assessable at MIP CT because of
      mural calcifications. All carotid arteries were assessable on volume-rendered
      images despite no depiction of the residual lumen at the site of narrowing in
      three cases of near occlusion. Correlations between angiography and helical CT
      were good. Axial, volume-rendered, and MIP images enabled correct classification
      of stenosis in 88%, 89%, and 90% of arteries, respectively. CT with volume
      rendering was slightly more sensitive for determining candidates for
      endarterectomy (i.e., those with > 70% stenosis and near occlusion); sensitivity
      was 100% and specificity, 92%. CONCLUSION: CT angiography with volume rendering
      enabled accurate evaluation of carotid disease, even when dense calcifications
      were present. However, no definite advantage over currently available techniques
      for CT measurement of stenosis severity was found.

PMID- 10207468
TI  - Reassessment of pulmonary angiography for the diagnosis of pulmonary embolism:
      relation of interpreter agreement to the order of the involved pulmonary arterial
      branch.
AB  - PURPOSE: To reassess the validity of conventional pulmonary angiography in the
      diagnosis of pulmonary embolism (PE) in main, lobar, segmental, and subsegmental
      pulmonary arteries. MATERIALS AND METHODS: Data are from examinations of 375
      patients with angiographically diagnosed PE who participated in the Prospective
      Investigation of Pulmonary Embolism Diagnosis. The average co-positivity of
      readings of the pulmonary angiograms was evaluated in relation to the order of
      the largest pulmonary artery that showed PE. RESULTS: Among 217 patients whose
      angiograms showed PE in main or lobar pulmonary arteries, as well as in smaller
      orders of arteries, there was an average co-positivity of 98% (95% Cl = 96%,
      98%). Among 136 patients whose pulmonary angiograms showed PE in segmental or
      subsegmental pulmonary arteries but not in larger orders of arteries, the average
      co-positivity was 90% (95% Cl = 85%, 95%). Among 22 patients with PE limited to
      the subsegmental arteries, the average co-positivity was 66% (95% Cl = 46%, 86%).
      CONCLUSION: Conventional pulmonary angiography is not precise for the diagnosis
      of PE limited to subsegmental arteries. To evaluate subsegmental arteries,
      techniques that improve the visualization of PE in small arteries should be used.

PMID- 10207467
TI  - Aortoiliac and lower extremity arteries: comparison of three-dimensional dynamic
      contrast-enhanced subtraction MR angiography and conventional angiography.
AB  - PURPOSE: To determine the clinical feasibility of three-dimensional dynamic
      contrast agent-enhanced subtraction magnetic resonance (MR) angiography in
      patients with symptoms of lower extremity ischemia. MATERIALS AND METHODS: Twenty
      three patients suspected of having lower extremity ischemia underwent three
      dimensional dynamic contrast-enhanced subtraction MR angiography of the
      aortoiliac arteries and arteries of the lower extremity. As the reference
      standard, conventional angiography was also performed. For data analysis, the
      arterial system was divided into 10 segments. Each segment was classified as
      normal, mildly stenosed, moderately stenosed, severely stenosed, or occluded.
      RESULTS: At conventional angiography, 83 stenosed segments (14 mildly stenosed,
      16 moderately stenosed, 14 severely stenosed, and 39 occluded) were identified in
      a total of 423 segments. For the segments with more than mild stenosis, MR
      angiography was 97.1% sensitive and 99.2% specific. CONCLUSION: Three-dimensional
      dynamic contrast-enhanced subtraction MR angiography has high sensitivity and
      specificity. This technique is a noninvasive alternative to conventional
      angiography for screening patients suspected of having lower extremity ischemia.

PMID- 10207469
TI  - Clinically suspected pulmonary embolism: utility of spiral CT.
AB  - PURPOSE: To prospectively determine the utility of contrast material-enhanced
      spiral computed tomography (CT) in the examination of patients clinically
      suspected of having pulmonary embolism (PE). MATERIALS AND METHODS: One hundred
      ten patients clinically suspected of having PE were examined with contrast
      enhanced spinal CT and at least one other imaging modality: ventilation-perfusion
      scintigraphy, Doppler ultrasonography of deep leg veins, or pulmonary
      angiography. Chart review or telephone contact with the referring clinician was
      used to evaluate the contribution of spiral CT to the final clinical diagnosis.
      RESULTS: Spiral CT helped correctly identify 23 of 25 patients with PE
      (sensitivity, 92%). In 57 (67%) of the 85 patients without PE, spiral CT provided
      additional information that suggested or confirmed the alternate clinical
      diagnosis: pneumonia (n = 14), cardiovascular disease (n = 10), pulmonary
      fibrosis (n = 7), trauma (n = 6), malignancy (n = 5), pleural disease (n = 4),
      postoperative changes (n = 4), and other (n = 7). In the remaining 28 patients,
      spiral CT scans were normal (n = 12), failed to produce findings supportive of
      the final clinical diagnosis (n = 13), or were false-positive for PE (n = 3;
      specificity, 96%). CONCLUSION: Spiral CT has good sensitivity and specificity for
      the diagnosis of PE. In the majority of patients who do not have PE, it also
      provides important ancillary information for the final diagnosis.

PMID- 10207470
TI  - Pulmonary infections after bone marrow transplantation: clinical and radiographic
      findings.
AB  - PURPOSE: To assess the clinical and radiographic findings of pulmonary infections
      diagnosed by using invasive means. MATERIALS AND METHODS: Fifty-nine episodes of
      pulmonary infection were diagnosed in 52 (7.2%) of a consecutive series of 725
      adult bone marrow transplant recipients. Causative organisms, time of diagnoses,
      radiographic patterns, and mortality rates were reviewed. RESULTS:
      Cytomegalovirus and Aspergillus species were the two most common pathogens,
      accounting for 22 and 17 episodes, respectively. During the first 30 days after
      bone marrow transplantation, fungi caused the majority (nine [82%] of 11
      episodes) of pulmonary infections; from days 31 to 100, viruses predominated (21
      [62%] of 34 episodes). Recipients of allogeneic transplants had a higher
      probability of developing Cytomegalovirus pneumonitis than did the recipients of
      autologous and syngeneic transplants (P < .001). Radiographic findings of
      Cytomegalovirus pneumonia consisted of parenchymal opacification (90%) and
      innumerable nodules smaller than 5 mm (29%); in two patients, radiographs were
      normal. Nodules, masses, or nodules and masses, present in nine (69%) of the 13
      patients with Aspergillus infection, were the most common radiographic findings
      in invasive aspergillosis. Bone marrow transplant recipients with a documented
      pulmonary infection were found to have a lower event-free survival than
      recipients without infection (P < .001). CONCLUSION: Opportunistic pathogens
      account for the majority of pulmonary infections requiring invasive diagnosis and
      tend to manifest at predictable times in the course of events following recovery
      from bone marrow transplantation. Cytomegalovirus, the most common pathogen,
      causes a spectrum of radiographic findings that includes normal findings.
      Occurrence of a pulmonary infection is associated with an increased mortality
      rate.

PMID- 10207471
TI  - Multinodular disease: anatomic localization at thin-section CT--multireader
      evaluation of a simple algorithm.
AB  - PURPOSE: To evaluate the interobserver variability and accuracy of an algorithm
      for anatomic localization of small nodules evident on thin-section computed
      tomographic (CT) images of the lungs. MATERIALS AND METHODS: Four experienced
      chest radiologists independently evaluated thin-section CT images in 58 patients
      by using an algorithm and a standard score sheet. Nodules were placed into four
      possible anatomic locations or categories: perilymphatic, random, associated with
      small airways disease, or centrilobular. Algorithm accuracy was assessed by
      comparing the localization by the observers to that expected for each specific
      disease in the study group on the basis of reports in the literature.
      Interobserver variability was assessed by placing cases into one of three groups:
      (a) complete concordance, (b) triple concordance, and (c) discordant. RESULTS:
      All observers agreed in 79% (46 of 58) of the cases with regard to nodule
      localization; three of the four concurred in an additional 17% (10 of 58). The
      observers were correct in 218 (94%) of 232 localizations in the 58 cases. There
      were no apparent differences in the number of either discordant or incorrect
      localizations between the observers. The most noteworthy source of error and of
      disagreement between observers was the confusion of perilymphatic and small
      airways disease-associated nodules in a small number of cases. CONCLUSION: The
      proposed algorithm is reproducible and accurate in the majority of cases and
      facilitates nodule localization at thin-section CT.

PMID- 10207473
TI  - Crossing vessels at the ureteropelvic junction: detection with contrast-enhanced
      color Doppler imaging.
AB  - PURPOSE: To investigate the feasibility of imaging crossing vessels at the
      ureteropelvic junction (UPJ) preoperatively by means of contrast agent-enhanced
      color Doppler imaging (CDI). MATERIALS AND METHODS: Twenty-nine patients (13
      female patients, 16 male patients; age range, 17-76 years; mean age, 45 years)
      with symptomatic UPJ obstruction were examined with CDI before and after
      intravenous infusion of the contrast agent. The type (i.e., arterial or venous)
      and position of the vessel relative to the UPJ (i.e., anterior or posterior) were
      assessed. The CDI findings were correlated with the surgical findings at
      laparoscopic pyeloplasty. RESULTS: Among the 29 patients, crossing vessels were
      detected with nonenhanced CDI in 15 patients, with enhanced CDI in 22 patients,
      and with laparoscopy in 23 patients. Enhanced CDI depicted crossing vessels in 22
      (96%) of the 23 laparoscopically confirmed cases compared with nonenhanced CDI,
      which depicted 15 (65%) of the 23 cases. The rate of detecting crossing vessels
      increased significantly with use of the contrast agent (P < .016, McNemar test).
      CONCLUSION: Compared with nonenhanced CDI, contrast-enhanced CDI significantly
      improves the detection of crossing vessels at the UPJ and is useful in the
      presurgical evaluation of UPJ obstruction.

PMID- 10207472
TI  - US guidance for thoracic biopsy: a valuable alternative to CT.
AB  - PURPOSE: To determine the role, accuracy, and selection criteria of
      ultrasonographic (US) guidance for biopsy for thoracic lesions. MATERIALS AND
      METHODS: Imaging-guided thoracic biopsies (n = 86) were performed in 84
      consecutive patients. US guidance was used for lesions abutting the chest wall;
      computed tomographic (CT) guidance was used for all masses surrounded by aerated
      lung. Mass location and size, guidance modality, histologic results, procedure
      time, and complications were recorded. RESULTS: Thirty-four lesions (19
      parenchymal, six pleural, six chest wall, three mediastinal) were amenable to US
      guided biopsy. The mean mass diameter was 4.3 cm, the mean number of passes was
      3.2, and the mean procedure time was 31.4 minutes. A histologic diagnosis was
      achieved in 31 (91%) patients, including all with small (< 2-cm) masses (n = 9).
      There was one case of pneumothorax. CT guidance was used in 52 (60%) of 86 cases.
      Lesions were parenchymal (n = 41), pleural (n = 1), and mediastinal and hilar (n
      = 10). The mean diameter was 2.9 cm, the mean number of passes was 2.3, and the
      mean procedure time was 45.2 minutes. A histologic diagnosis was achieved in 37
      (71%) patients, including 18 of 27 with a small mass. Complications included
      pneumothorax (n = 21) and parenchymal hemorrhage (n = 2). CONCLUSION: US is an
      effective and safe alternative to CT for guidance at biopsy of masses abutting
      the chest wall. Real-time US visualization allows accurate needle placement,
      shorter procedure time, and performance in debilitated and less cooperative
      patients.

PMID- 10207474
TI  - Diagnostic accuracy with US: remote radiologists' versus on-site radiologists'
      interpretations.
AB  - PURPOSE: To compare the diagnostic accuracy of radiologists interpreting static
      ultrasonographic (US) images electronically transmitted to an academic medical
      center (remote radiologists) with that of radiologists performing "hands-on" US
      at a community-based outpatient site (on-site radiologists). MATERIALS AND
      METHODS: During 8 months, 80 patients underwent pelvic US at a community-based
      outpatient site. Images were electronically transmitted to a remote medical
      center as they were acquired at the community site and were printed on a laser
      printer identical to the one used at the outpatient site. The reference standard
      for correct diagnosis was based on histopathologic findings (n = 13), additional
      imaging results (n = 34), or review by a second independent observer (n = 33).
      Both an on-site and a remote radiologist interpreted the images, and their
      interpretations were rated as agree, both correct; agree, both incorrect; or
      disagree. Cases of disagreement were rated as major or minor. RESULTS: On-site
      and remote radiologists agreed in 69 of 80 patients (86%), and both radiologists
      were correct in all of these cases. There were 10 minor discrepancies and one
      major discrepancy. The diagnostic accuracies of the one-site and remote
      radiologists were 92% and 94%, respectively. CONCLUSION: High levels of
      diagnostic accuracy can be achieved by radiologists interpreting static US
      images. Strict protocols and excellent communication between the radiologist and
      sonographer are necessary to avoid diagnostic errors.

PMID- 10207475
TI  - The goblet sign.

PMID- 10207476
TI  - Endometriomas: diagnostic performance of US.
AB  - PURPOSE: To determine the diagnostic performance of specific ultrasonographic
      (US) features in discriminating endometriomas from other adnexal masses.
      MATERIALS AND METHODS: Two sonologists independently reviewed the sonograms of
      252 adnexal masses in 226 women and recorded US features by using a standardized
      checklist. The diagnostic performance of specific US features and overall
      reviewer impression in discriminating endometriomas from other adnexal masses
      were evaluated. RESULTS: There were 40 endometriomas. Diffuse low-level internal
      echoes were present in 38 (95%) endometriomas and 40 (19%) nonendometriomas
      (positive likelihood ratio, 5). The positive likelihood ratio for the diagnosis
      of endometrioma increased to 8 if masses with neoplastic features at gray-scale
      US were excluded, allowing identification of 30 endometriomas (75%). The presence
      of multilocularity or hyperechoic wall foci further increased the positive
      likelihood ratio to 48, allowing the identification of 18 endometriomas (45%).
      CONCLUSION: An adnexal mass with diffuse low-level internal echoes and absence of
      particular neoplastic features is highly likely to be an endometrioma if
      multilocularity or hyperechoic wall foci are present. A patient with a mass with
      diffuse low-level internal echoes and other US features may benefit from
      additional imaging.

PMID- 10207477
TI  - Tubal obstruction after ligation reversal surgery: results of catheter
      recanalization.
AB  - PURPOSE: To evaluate the role of transcervical fallopian tube catheterization in
      restoring tubal patency after ligation reversal surgery. MATERIALS AND METHODS:
      Twenty-four women with tubal obstruction after ligation reversal surgery
      underwent selective salpingography and tubal recanalization. RESULTS: Patency was
      established in 26 (68%) of 38 anastomotic tubes without complication. In the 13
      patients who were followed up and who could conceive only via a recanalized
      anastomotic tube, there were six (46%) pregnancies: two (15%) successful uterine
      pregnancies, two (15%) early spontaneous abortions, and two (15%) tubal
      pregnancies. The mean time from procedure to conception was 2 months. CONCLUSION:
      Patency of fallopian tubes not visualized at hysterosalpingography after ligation
      reversal surgery can be established 68% of the time with selective
      salpingography. In some patients, selective salpingography can be therapeutic. If
      subsequent conception occurs in these patients, it occurs shortly after the
      catheterization procedure.

PMID- 10207478
TI  - Cortical maturation in normal and abnormal fetuses as assessed with prenatal MR
      imaging.
AB  - PURPOSE: To establish the appearance of normal fetal cortical development in
      utero and compare it with the appearance of abnormal cortical development.
      MATERIALS AND METHODS: Magnetic resonance (MR) images of the brain in 53 normal
      and 40 abnormal fetuses at 14-38 weeks gestational age (GA) were reviewed. The
      GAs at the time of MR imaging visualization of the fissures or sulci were
      compared with the GA guidelines based on neuroanatomic studies. RESULTS: In
      normal fetuses, the sulcation landmarks appeared on MR images in the order
      predicted by using anatomic studies, with a 0-8-week lag in the MR imaging
      visualization of the sulci compared with the reported time of visualization of
      the sulci in anatomic specimens. When landmarks were grouped by range of GAs, the
      expected MR imaging sulcation landmarks in the group with younger GAs than the
      actual GA were seen in 50 of 53 (94%) normal fetuses, in five of nine fetuses
      (56%, P < .05) with isolated mild ventriculomegaly, and in 24 of 31 fetuses (77%,
      P < .05) with other CNS anomalies. CONCLUSION: Normal fetal cortical maturation
      at MR imaging follows a predictable course that is slightly delayed compared with
      that described in neuroanatomic specimens. This maturation is often further
      delayed in fetuses with CNS abnormalities.

PMID- 10207479
TI  - MR imaging of human brain at 3.0 T: preliminary report on transverse relaxation
      rates and relation to estimated iron content.
AB  - PURPOSE: To determine the transverse relaxation rates R2 and R2' from several
      gray matter regions and from frontal cortical white matter in healthy human
      brains in vivo and to determine the relationship between relaxation rates and
      iron concentration [Fe]. MATERIALS AND METHODS: Six healthy adults aged 19-42
      years underwent thin-section gradient-echo sampling of free induction decay and
      echo magnetic resonance (MR) imaging at 3.0 T. Imaging covered the mesencephalon
      and basal ganglia. RESULTS: Relaxation rates (mean +/- SD) were highest in globus
      pallidus (R2 = 25.8 seconds-1 +/- 1.1, R2' = 12.0 seconds-1 +/- 2.1) and lowest
      in prefrontal cortex (R2 = 14.4 seconds-1 +/- 1.8, R2' = 3.4 seconds-1 +/- 1.1).
      Frontal white matter measurements were as follows: R2 = 18.0 seconds-1 +/- 1.2
      and R2' = 3.9 seconds-1 +/- 1.2. For gray matter, both R2 and R2' showed a strong
      correlation (r = 0.92, P < .001 and r = 0.90, P < .001, respectively) with [Fe].
      Although the slopes of the regression lines for R2' versus [Fe] and for R2 versus
      [Fe] were similar, the iron-independent component of R2' (2.2 seconds-1 +/- 0.6),
      the value when [Fe] = 0, was much less than that of R2 (12.7 seconds-1 +/- 0.7).
      CONCLUSION: The small iron-independent component R2', as compared with that of
      R2, is consistent with the hypothesis that R2' has higher iron-related
      specificity.

PMID- 10207480
TI  - Differences between relapsing-remitting and chronic progressive multiple
      sclerosis as determined with quantitative MR imaging.
AB  - PURPOSE: To investigate the cross-sectional relationships among multiple
      quantitative brain magnetic resonance (MR) imaging measurements in patients with
      relapsing-remitting versus chronic progressive multiple sclerosis (MS). MATERIALS
      AND METHODS: Thirty-eight patients with MS (relapsing-remitting, 26, chronic
      progressive, 12) were examined. Lesion volume on T2-weighted MR images, contrast
      material-enhancing lesion volume, percentage of brain parenchymal volume (brain
      volume/[brain volume + cerebrospinal fluid volume), and magnetization transfer
      ratio histogram peak height for the whole brain were calculated. RESULTS:
      Significant negative correlation was noted between volume on T2-weighted images
      and magnetization transfer ratio histogram peak height for both the relapsing
      remitting and chronic progressive groups (P < .001 for both). A positive
      correlation was demonstrated for lesion volume on T2-weighted images and
      enhancing lesion volume in the relapsing-remitting group (P < .01) but not in the
      chronic progressive group. Negative correlations were demonstrated for enhancing
      lesion volume and magnetization transfer ratio histogram peak height (P = .02),
      for Expanded Disability Status Scale score and magnetization transfer histogram
      peak height (P = .02), and for Expanded Disability Status Scale score and
      percentage of brain parenchymal volume in the relapsing-remitting group (P =
      .004) but not in the chronic progressive group. CONCLUSION: The cross-sectional
      relationships among multiple quantitative brain MR imaging measurements are
      different between relapsing-remitting and chronic progressive MS.

PMID- 10207481
TI  - Uveal melanoma: correlation of histopathologic and radiologic findings by using
      thin-section MR imaging with a surface coil.
AB  - PURPOSE: To evaluate whether the different signal intensities at magnetic
      resonance (MR) imaging of melanoma are associated with a higher content of
      melanin. MATERIALS AND METHODS: In a prospective study, MR imaging and
      ophthalmoscopic examination findings in 42 patients (19 women, 23 men; age range,
      30-87 years) with uveal melanoma were compared with histopathologic examination
      findings obtained after enucleation. MR imaging was performed with 2-mm sections
      by using a 5-cm surface coil. T1- and T2-weighted images were obtained before and
      after contrast material administration. RESULTS: In 33 (79%) of the patients,
      there was homogeneous tumor pigmentation, whereas in nine (21%) patients, there
      was inhomogeneous bipartite tumor pigmentation. Compared with the histopathologic
      data, the results of qualitative evaluation were accurate in 29 (58%) of 50 and
      in 26 (53%) of 49 tumorous areas on T1- and T2-weighted images, respectively.
      Quantitative evaluation yielded better results, especially at T1-weighted
      imaging; an 86% correlation was found. Because of methodological reasons, only
      the superficial pigmentation of inhomogeneous tumors could be evaluated with
      ophthalmoscopy. CONCLUSION: Thin-section MR imaging of the eye enables an
      accurate prediction of melanomatous pigmentation with quantitative evaluation of
      plain T1-weighted images and is superior to ophthalmoscopy in cases of
      inhomogeneous pigmentation.

PMID- 10207482
TI  - Injuries of the pectoralis major muscle: evaluation with MR imaging.
AB  - PURPOSE: To demonstrate that magnetic resonance (MR) imaging allows evaluation of
      injuries of the pectoralis major muscle. MATERIALS AND METHODS: Fifteen men
      underwent MR imaging after injury of the pectoralis major muscle. Most of the
      patients (nine of 15) were injured while lifting weights, notably bench-pressing.
      The injuries were evaluated for abnormal morphology and signal intensity,
      specifically the site of injury, degree of tearing, and amount of tendon
      retraction. RESULTS: Six injuries occurred at the musculotendinous junction, and
      five were treated conservatively; eight of the nine cases of distal tendon
      avulsion were treated with primary surgical repair. The MR imaging findings were
      confirmed in the nine cases treated surgically. Complete tears (three of 15) were
      less common than partial tears (12 of 15). The sternal and clavicular heads were
      torn in 10 patients, only the clavicular head was torn in two patients, and only
      the sternal head was torn in three patients. Acute tears (10 of 15) demonstrated
      hemorrhage and edema, whereas chronic tears (five of 15) demonstrated fibrosis
      and scarring. There was a variable amount of tendon retraction. CONCLUSION: MR
      imaging allows accurate evaluation of injuries of the pectoralis major muscle and
      enables identification of patients who would benefit from surgical repair.

PMID- 10207483
TI  - Diagnosis please. Case 8: solitary intraductal papilloma.

PMID- 10207484
TI  - Stereotactic, automated, large-core needle biopsy of nonpalpable breast lesions:
      false-negative and histologic underestimation rates after long-term follow-up.
AB  - PURPOSE: To determine the rate and causes of false-negative findings and
      histologic underestimates at stereotactic biopsy of nonpalpable breast lesions.
      MATERIALS AND METHODS: Stereotactic, 14-gauge, automated, large-core needle
      biopsy (LCNB) was performed in 483 consecutive nonpalpable breast lesions.
      Excision was advised for the 143 carcinomas, 25 atypical ductal hyperplasia (ADH)
      lesions, and five radial scars. Mammographic follow-up was advised for the benign
      lesions without a repeat biopsy. RESULTS: Of the 310 benign lesions, 259
      underwent mammographic follow-up at 6-85 months (median, 55 months) without
      repeat biopsy, 48 underwent repeat biopsy and three were lost to follow-up. On
      the basis of the histologic diagnosis of carcinoma at surgical biopsy, diagnosis
      with LCNB was not correct (i.e., disease was underestimated at histologic
      examination) in 14 (58%) of 24 ADH lesions and two (40%) of five radial scars.
      Two (1.2%) of 161 lesions with a final diagnosis of carcinoma were benign at LCNB
      but malignant at repeat biopsy (i.e., false-negative findings at LCNB). Repeat
      biopsy was prompted by mammographic progression at 6 and 18 months after LCNB.
      CONCLUSION: The false-negative rate with LCNB was 1.2% in this study and 4.0% in
      the literature. The presence of carcinoma in ADH and radial scar lesions was
      often underestimated.

PMID- 10207485
TI  - Value of combined FDG PET and MR imaging in the evaluation of suspected recurrent
      local-regional breast cancer: preliminary experience.
AB  - PURPOSE: To assess the performance and potential clinical effects of combined 2
      [fluorine 18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)
      and magnetic resonance (MR) imaging of the axilla and brachial plexus in patients
      suspected of having local-regional breast cancer metastases. MATERIALS AND
      METHODS: Upper-body FDG PET and axillary and supraclavicular MR imaging were
      performed in 10 patients (age range, 45-71 years) with clinical findings
      suggestive of breast cancer metastases. Medical records were reviewed
      retrospectively. Imaging findings were correlated with clinical data and follow
      up findings in all patients. Surgical findings were available in four patients.
      RESULTS: Nine patients had local-regional breast cancer metastases. MR imaging
      was diagnostic for tumor in five patients and was indeterminate in four patients
      with axillary or chest wall metastases. With FDG PET, metastatic tumor was
      positively identified in all nine patients. MR imaging was useful for determining
      the relationship of metastatic tumor to axillary and supraclavicular
      neurovascular structures. FDG PET helped confirm metastases in patients with
      indeterminate MR imaging findings and depicted unsuspected metastases outside the
      axilla. CONCLUSION: MR imaging and FDG PET are complementary in detecting and
      characterizing local-regional breast cancer metastases. Combined FDG PET and MR
      imaging provide useful treatment-planning data for patients clinically suspected
      of having recurrent axillary or supraclavicular breast cancer.

PMID- 10207486
TI  - Radioaerosol scintigraphy in infants and children born to mothers with HIV
      disease. Pediatric Pulmonary and Cardiovascular Complications (of Vertically
      Transmitted Human Immunodeficiency Virus) Study Group.
AB  - PURPOSE: To determine the usefulness of technetium 99m diethyltriaminepentacetic
      acid (DTPA) radioaerosol inhalation-clearance scintigraphy for early detection of
      pulmonary complications of human immunodeficiency virus (HIV) disease in
      children. MATERIALS AND METHODS: A total of 301 studies were performed in 132 HIV
      positive children (group 1; mean age, 46.6 months). In children born to HIV
      positive mothers (group 2), 273 studies were performed in 160 children who
      eventually were proved to be HIV negative (mean age, 10.3 months), and 80 studies
      were performed in 47 HIV-positive children (mean age, 15.6 months). Radioaerosol
      studies were performed by using commercially available radioaerosol nebulizers.
      Pulmonary clearance half-time was measured by using conventional gamma camera
      computer systems. Radioaerosol results were correlated with indexes of pulmonary
      health and function. RESULTS: The HIV-negative, group 2 children had a mean
      radioaerosol clearance half-time (58.1 minutes; 162 studies in 108 children)
      similar to that reported in healthy adults. Group 1 children with pulmonary
      involvement exhibited a faster mean clearance half-time (28.6 minutes) than did
      children without evidence of pulmonary involvement from either group 1 or group 2
      (P < .05). A faster pulmonary clearance rate did not simply reflect the presence
      of chest disease that also was detectable on radiographs (P = .3). CONCLUSION:
      Quantitative DTPA radioaerosol clearance studies may provide useful information
      about pulmonary involvement in selected children with HIV disease.

PMID- 10207487
TI  - FDG imaging of lung nodules: a phantom study comparing SPECT, camera-based PET,
      and dedicated PET.
AB  - PURPOSE: To evaluate 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) imaging of
      simulated lung nodules in a realistic chest phantom by using attenuation
      corrected and non-attenuation-corrected 511-keV single photon emission computed
      tomography (SPECT), camera-based positron emission tomography (PET), and
      dedicated PET imaging. MATERIALS AND METHODS: Spheres with diameters of 6, 10,
      13, and 22 mm were placed in the lungs of an anthropomorphic chest phantom to
      simulate nodules. The lungs, nodules, chest wall, and mediastinum were filled
      with fluorine-18 activities based on the average radionuclide concentrations in
      those structures from analysis of attenuation-corrected dedicated FDG PET scans.
      The image sets were evaluated visually and quantitatively by using contrast and
      signal-to-noise ratios. RESULTS: Attenuation correction reduced the artificially
      high apparent uptake in the lungs, restored the spherical shape to the nodules,
      and provided an accurate outer body contour with appropriate intensity. Dedicated
      PET depicted all four nodules, camera-based PET depicted the three largest
      nodules, and SPECT depicted the two largest nodules. Lesion contrast was better
      on the attenuation-corrected images than on the non-attenuation-corrected images.
      The signal-to-noise ratio generally was improved with attenuation correction.
      CONCLUSION: Attenuation correction results in many changes in the images and
      improves lesion detection.

PMID- 10207488
TI  - Gadolinium as a CT contrast agent: assessment in a porcine model.
AB  - PURPOSE: To investigate the use of gadolinium as a computed tomographic (CT)
      contrast agent. MATERIALS AND METHODS: In vitro attenuation measurements of
      multiple dilutions of gadodiamide and ioversol were compared. In three pigs, 50
      mL boluses of undiluted gadodiamide were injected intravenously at 2 mL/sec, and
      repeated single-level scans were obtained through the lung bases, liver, and
      kidneys. The doses of 0.8-1.0 mmol of gadolinium per kilogram of body weight were
      approximately three times the highest doses currently used in patients.
      Enhancement was determined from attenuation measurements in the aorta, pulmonary
      arteries, liver, and kidneys. RESULTS: In vitro, the attenuation of undiluted
      gadodiamide (3,069 HU) was equivalent to that of ioversol diluted to 106 mg of
      iodine per milliliter and at equimolar concentrations was 50% greater than that
      of ioversol. The magnitude of and time to peak enhancement were 141 HU and 27
      seconds (n = 3) for the aorta; 168 HU and 21 seconds (n = 3) for the pulmonary
      arteries; 23 HU and 65 seconds (n = 2) for the liver; and 63 HU and 32 seconds (n
      = 1) for the kidneys. Time-attenuation curves revealed a useful duration of
      enhancement of 20-30 seconds for the aorta and pulmonary arteries. CONCLUSION:
      Gadolinium produces good vascular enhancement, adequate renal enhancement, and
      suboptimal hepatic enhancement. Further study is needed to determine the safety
      of the gadolinium dose required to produce similar enhancement in patients.

PMID- 10207489
TI  - Premature partial closure and other deformities of the growth plate: MR imaging
      and three-dimensional modeling.
AB  - PURPOSE: To examine growth plates of the distal femur and tibia with magnetic
      resonance (MR) imaging to detect bone bridges and other deformities in children.
      MATERIALS AND METHODS: Thirteen children (nine boys and four girls, aged 5-13
      years; mean age, 9.8 years) were referred because of suspected or known bone
      bridging of the growth plate. Among the 13 patients, 10 had Salter-Harris
      fractures of the knee or ankle, two had Blount disease, and one had neonatal
      sepsis. Fat-saturated spoiled gradient-recalled images enabled reconstruction of
      a three-dimensional model of the growth plate. Patients underwent one to four MR
      examinations. RESULTS: Nine patients had bone bridging of less than 1% to 39% of
      the area of the growth plate. On MR images obtained in the growth plate of five
      patients, a stripe of low signal intensity indicated fracture. On MR images
      obtained in three patients, intrusions of growth plate cartilage into the
      metaphysis were seen to increase in depth over time. MR images obtained in four
      patients showed no bridges. In the two patients who underwent surgery, excellent
      correspondence was found between MR findings and surgical observations.
      CONCLUSION: Marked undulation or splitting of the growth plate may occur with
      fixation of some cartilage in the metaphysis or epiphysis while growth continues.
      The configuration of the growth plate and bone bridges can be accurately mapped
      with MR imaging. Treatment planning is facilitated.

PMID- 10207490
TI  - Subcutaneous granuloma annulare: MR imaging features in six children and
      literature review.
AB  - PURPOSE: To describe the magnetic resonance (MR) imaging findings of subcutaneous
      granuloma annulare (SGA), a rare mass of early childhood. MATERIALS AND METHODS:
      MR imaging studies and clinical records in six children aged 2 1/2-4 years in
      whom SGA was diagnosed between 1993 and 1997 were retrospectively reviewed. All
      MR imaging examinations included T1-weighted and fast spin-echo T2-weighted
      sequences. Three children received intravenous contrast material. The diagnosis
      was established by using excisional biopsy results, with confirmation by means of
      characteristic features in mucin-stained specimens. RESULTS: All children
      presented with a nontender, nonmobile mass. The lesion in all six children was
      confined to the pretibial (n = 5) or prepatellar (n = 1) soft tissues. MR imaging
      characteristics were uniform. Masses were subcutaneous in location and had ill
      defined margins. On T1-weighted images, the lesion was isointense or slightly
      hyperintense to muscle. On T2-weighted images, the signal intensity was more
      heterogeneous, but the lesion was predominantly hyperintense. In three children
      who received contrast material, the lesion enhanced nearly homogeneously.
      CONCLUSION: Although SGA can often be diagnosed on the basis of clinical
      characteristics, MR imaging may be requested by practitioners unfamiliar with the
      lesion. In these cases, with recognition of typical MR imaging features, a
      limited biopsy and specific histologic preparation that includes mucin staining
      can be recommended.

PMID- 10207491
TI  - Lung air spaces: MR imaging evaluation with hyperpolarized 3He gas.
AB  - Thirty-two magnetic resonance imaging examinations of the lungs were performed in
      16 subjects after inhalation of 1-2 L of helium 3 gas that was laser polarized to
      10%-25%. The distribution of the gas was generally uniform, with visualization of
      the fissures in most cases. Ventilation defects were demonstrated in smokers and
      in a subject with allergies. The technique has potential for evaluating small
      airways disease.

PMID- 10207492
TI  - Peripherally inserted central venous catheters: success of scalp-vein access in
      infants and newborns.
AB  - The authors assessed the feasibility of placing peripherally inserted central
      venous catheters via scalp veins in infants and newborns. In 60 newborns and
      infants, aged 3 days to 10 months, placement of 62 2-F peripherally inserted
      central venous catheters was attempted with scalpvein access. The tip location
      was central in 30 of the 62 catheters (48%) and long peripheral intravenous in 17
      (27%); access failed in 15 (24%). Scalp-vein access for peripherally inserted
      central venous catheters offers a safe and effective alternative route for
      gaining central venous access in infants and newborns.

PMID- 10207493
TI  - Pancreas: does hyoscyamine butylbromide increase the diagnostic value of helical
      CT?
AB  - Among 50 patients referred for helical computed tomography (CT) of the pancreas,
      24 randomly selected patients received 40 mg of hyoscyamine butylbromide to
      evaluate whether its administration improved image quality and diagnostic
      findings. Differences between the groups were not statistically significant. It
      was therefore concluded that hyoscyamine butylbromide does not contribute a
      diagnostic advantage at helical CT of the pancreas.

PMID- 10207494
TI  - Upper gastrointestinal tract malignant obstruction: initial results of palliation
      with a flexible covered stent.
AB  - The authors treated 21 patients with inoperable upper gastrointestinal tract
      malignant obstruction from the esophagus to the duodenum by means of intubation
      with a flexible covered stent with fluoroscopic guidance. Stent placement was
      successful and relief of dysphagia was immediate in 18 (86%) patients, without
      serious complication. The average dysphagia score decreased from 2.6 (dysphagia
      to liquids) to 1.0 (dysphagia to normal solid food). Placement of a flexible
      covered stent provides easy, safe, and effective palliation of upper
      gastrointestinal malignant obstruction.

PMID- 10207495
TI  - Dry versus conventional laser imagers: film properties and image quality.
AB  - The authors compared image quality and stability with a dry laser imager versus a
      conventional wet laser imager. Hard copies of 56 magnetic resonance imaging and
      computed tomographic studies were analyzed for gray-scale distribution and
      temperature stability. Results with the dry laser imager did not reach the
      quality of results with a wet laser imager, but the performance and ecologic
      criteria were sufficient to make use of this technique advantageous.

PMID- 10207496
TI  - Medicine: a learned profession.

PMID- 10207497
TI  - Selective vascular ligation versus embolization in obstetric hemorrhage.

PMID- 10207498
TI  - Differentiation of benign versus malignant breast disease.

PMID- 10207499
TI  - Can the use of preoperative MR imaging reduce local recurrence rates in patients
      with retroareolar breast cancer who undergo breast-conservation surgery?

PMID- 10207500
TI  - Statistical evaluation of agreement.

PMID- 10207501
TI  - Growth hormone and the somatopause.

PMID- 10207502
TI  - Frailty and the somatopause.

PMID- 10207503
TI  - Placental development and fetal growth in growth hormone-treated ewes.
AB  - The effects of recombinant bovine growth hormone (bGH) treatment of pregnant ewes
      on maternal metabolism, placental development and fetal growth were examined in
      two studies. In a preliminary study (experiment one), single-bearing ewes were
      treated by twice-daily subcutaneous injection for 7 days with bGH (n = 8) at a
      dose of 0.15 mg/kg LW/day or with saline (n = 8) between days 101 and 107 of
      gestation inclusive. In experiment two, single- and twin-bearing ewes were
      treated for 14 days with bGH (0.15 mg/kg L W/day) (n = 10) or saline (n = 10)
      between days 70 and 83 or days 98 and 111 of gestation inclusive. Ewes were
      killed on the day following termination of bGH treatment and fetal and placental
      measurements recorded. Maternal plasma concentrations of GH, IGF-I and insulin
      were higher (P < 0.001) in bGH-treated ewes relative to saline-treated ewes in
      both experiments. Consistent across experiments was an increase (P < 0.05) in the
      weight of the myoendometrium in bGH-treated ewes. Treatment with bGH also
      increased the total weight of the gravid uterus (P < 0.05) in both experiments.
      Weights of the uterine fluids were increased by bGH in experiment one (P < 0.05),
      but an effect of the same magnitude could not be repeated in experiment two. In
      experiment one, there was a tendency towards increased mean fetal body weights
      after growth hormone treatment, although the effect was non-significant. In
      experiment two, treatment with bGH was associated with significantly (P < 0.05)
      higher fetal weights, but only at the later stage of gestation (day 112). This
      effect was additive with that of fetal rank. Exogenous bGH treatment had little
      discernible effect on measures of placental size. It is concluded that
      administration of exogenous bGH to pregnant ewes can stimulate fetal growth, but
      only after about day 100 of gestation. This response seems most likely to reflect
      changes in maternal nutrient partitioning or placental function, rather than
      placental size. These studies suggest a role for growth hormone of maternal or
      placental origin in the regulation of fetal growth.

PMID- 10207504
TI  - Differences in reproducibility and peak growth hormone responses to repeated
      testing with various stimulators in healthy adults.
AB  - In healthy adults, GH responses to provocative testing are variable between
      subjects. Information on the intra-subject variability is limited, despite the
      importance attached to GH stimulation tests in the diagnosis of GH deficiency. We
      have investigated and compared the variability of different GH stimulation tests
      in a group of healthy control subjects. In 16 healthy non-obese adults, two
      insulin tolerance tests (ITT) (0.15 IU/kg body weight i.v. and a fall in blood
      glucose < or = 2.2 mmol/l) two GHRH tests (1 microgram/kg body weight i.v.), and
      two clonidine (CLO) (300 micrograms p.o.) + GHRH (60 min later) tests were
      performed in the morning after an overnight fast. A pyridostigmine (PD) (120 mg
      p.o. 60 min before GHRH) + GHRH test was performed twice in an extended group of
      31 healthy adult subjects. A wide range of GH responses was observed. Both during
      the ITT and the GHRH test, low values in the range generally recognized to
      reflect impairment of GH secretory status were encountered. The median (range)
      peak GH responses in tests 1 and 2 were: (a) ITT: 14.4 micrograms/l (4.1-71.1)
      and 14.0 micrograms/l (0.09-69.5), (b) GHRH test: 21.7 micrograms/l (0.71-56.2)
      and 18.4 micrograms/l (1.6-55.1); (c) CLO + GHRH test: 57.4 micrograms/l (22.9
      209) and 65.8 micrograms/l (12.2-206); (d) PD + GHRH test: 36.5 micrograms/l (9.1
      125) and 44.6 micrograms/l (6.3-101). The coefficients of variation (CV) were:
      58% (ITT), 45% (GHRH), 46% (CLO + GHRH) and 26% (PD + GHRH). The peak GH
      responses were significantly different in all tests (CLO + GHRH > PD + GHRH >
      GHRH > ITT). In the individual subject, there was no systematic correlation
      between the peak GH responses in the different stimulation tests. In conclusion,
      we found that the stimulated GH responses were highly variable in all tests, and
      that the peak GH responses differed. Test results in patients should be evaluated
      against test-specific reference values, and caution is justified in the
      interpretation of low responses in a single test.

PMID- 10207505
TI  - Characterization and partial purification of the insulin-like growth factor (IGF)
      dependent IGF binding protein-4-specific protease from human fibroblast
      conditioned media.
AB  - Insulin-like growth factors (IGFs) are one of the most potent stimulators of cell
      growth. IGFs are modulated by six high affinity binding proteins (IGFBPs) which
      are, in turn, regulated through post-translational modifications such as
      proteolysis. In the conditioned media of human fibroblasts, IGFBP-4 is cleaved by
      an apparently novel IGFBP-4-specific protease that requires IGF for functional
      activity. We have used several biochemical manipulations, including size
      exclusion chromatography, native gel electrophoresis, chaotropic salt
      precipitation, hydrophobic interaction chromatography, ion exchange
      chromatography, isoelectric focusing, lectin affinity chromatography, and metal
      chelating affinity chromatography to both characterize and partially purify the
      IGF-dependent IGFBP-4 protease. Our results indicate that this protease is a
      highly glycosylated, Zn+2 binding metalloprotease with a native molecular weight
      greater than 200 kDa.

PMID- 10207506
TI  - Growth hormone binding protein correlates strongly with leptin and percentage
      body fat in GH-deficient adults, is increased by GH replacement but does not
      predict IGF-I response.
AB  - GH-binding protein (GHBP) corresponds to the extracellular domain of the GH
      receptor (GHR) and has been shown to be closely related to body fat. This study
      aimed to examine the inter-relationship between GHBP, leptin and body fat, and to
      test the hypothesis that GHBP is modified by GH replacement in GH-deficient
      adults and predicts IGF-I response. Twenty adults, mean age 47 years (range 20
      69) with proven GH deficiency were randomly allocated to either GH (up to 0.25
      U/kg/week in daily doses) or placebo for 3 months before cross-over to the
      opposite treatment. Plasma GHBP and leptin were measured at baseline and 2, 4, 8
      and 12 weeks after each treatment. Whole body composition was measured at
      baseline by dual-energy X-ray absorptiometry (DEXA). There was a strong
      correlation between baseline leptin and GHBP (r = 0.88, P < 0.0001) and between
      baseline GHBP and percentage body fat, (r = 0.83, P < 0.0001). Mean GHBP levels
      were higher on GH compared with placebo, 1.53 +/- 0.28 vs 1.41 +/- 0.25nM, P =
      0.049. There was no correlation between baseline IGF-I and GHBP (r = -0.049, P =
      0.84), and GHBP did not predict IGF-I response to GH replacement. The close inter
      relationship between GHBP, leptin and body fat suggests a possible role for GHBP
      in the regulation of body composition. GHBP is increased by GH replacement in GH
      deficient adults, but does not predict biochemical response to GH replacement.

PMID- 10207508
TI  - Evidence supporting a direct suppressive effect of growth hormone on serum IGFBP
      1 levels. Experimental studies in normal, obese and GH-deficient adults.
AB  - It has occasionally been suggested that GH directly suppresses circulating IGFBP
      1 levels, although it is generally believed that such an effect is secondary to a
      GH-induced increase in insulin levels. We present data from several experiments
      in which the effects of GH on IGFBP-1 could be studied more extensively. In
      normal subjects (n = 36), an i.v. GH bolus caused a small but significant
      decrease in plasma IGFBP-1 concentrations without changes in insulin [IGFBP-1
      (microgram/l): 2.6 +/- 0.3 (GH) vs 3.2 +/- 0.4 (placebo), P < 0.05]. Conversely,
      a 28-h somatostatin infusion with and without GH administration during fasting in
      normal subjects yielded higher IGFBP-1 levels in the non-GH substituted study
      [50.5 +/- 5.3 (GH-suppression) vs 22.6 +/- 5.6 (GH-substitution), P < 0.01],
      comparable with an increased concentration of IGFBP-1 during fasting in GH
      deficient patients without usual GH substitution [23.4 +/- 7.6 (GH pause) vs 14.1
      +/- 4.9 (GH substitution), P < 0.01]. In both fasting studies insulin levels
      remained stable. During a hypocaloric diet, long-term GH treatment in obesity
      lead to a significant decline in IGFBP-1 level (2.3 +/- 0.6 vs 1.2 +/- 0.2, P <
      0.01), while no changes were found in the placebo group. Again, insulin levels
      remained equally low in both studies. Finally, a significant rebound increase in
      IGFBP-1 level in response to insulin induced hypoglycemia was only observed among
      GH-deficient patients, but not in control subjects, the latter of whom responded
      to hypoglycemia with a significant increase in serum GH levels [23.2 +/- 7.2
      (GHDA) vs 2.5 +/- 0.3 (controls), P < 0.01]. In conclusion, a suppressive effect
      of GH on IGFBP-1 appears to be unmasked in the presence of low or suppressed
      insulin levels, making GH a potential regulator of IGF-1 bioactivity in a
      hitherto unrecognized way.

PMID- 10207507
TI  - Long-term administration of adrenocorticotropin modulates the expression of IGF-I
      and TGF-beta 1 mRNAs in the rat adrenal cortex.
AB  - The effects of long-term adrenocorticotropin (ACTH) therapy on the expression of
      IGF-I and TGF-beta 1 on rat adrenal cortex was investigated. ACTH (0.1 mg/kg/day)
      or saline as control was injected intraperitoneally in 5-week-old Wistar rats
      every day for 4 weeks. ACTH significantly increased adrenal weight (P < 0.05) and
      serum corticosterone (P < 0.05). Competitive RT-PCR analysis on the
      adrenocortical mRNA showed increased IGF-I (P < 0.01) at 4 weeks of ACTH and
      increased TGF-beta 1 (P < 0.01) at 1 week of ACTH compared the control group.
      ACTH also significantly increased proliferating cell nuclear antigen mRNA level
      (P < 0.01), at 4 weeks of treatment, which correlated with IGF-I level (P <
      0.01), but correlated negatively with ACTH-stimulated TGF-beta 1 level (P <
      0.05). There was a weak correlation between IGF-I and serum corticosterone (P <
      0.05), and between TGF-beta 1 mRNA levels and serum corticosterone concentration
      (P < 0.05). Histologically, ACTH induced hypertrophy in the zona fasciculata
      cells and increased the clear cells containing lipid deposits.
      Immunohistochemistry showed that IGF-I peptide was mainly expressed in the
      periphery of the zona fasciculata at 4 weeks of ACTH therapy, while the same
      therapy caused a slight increase in TGF-beta 1 expression in the same area. Our
      results show that an increase in adrenocortical growth resulting from ACTH
      treatment is associated with an increase in IGF-I mRNA expression but only a
      transient increase in TGF-beta 1 mRNA expression.

PMID- 10207509
TI  - Hepatic expression of growth hormone receptor/binding protein and insulin-like
      growth factor I genes in uremic rats. Influence of nutritional deficit.
AB  - The molecular basis for GH resistance in chronic renal failure is unknown. It may
      partly reside in a decreased number of hepatic GH receptors and subsequently
      reduced IGF-I synthesis. To investigate the hepatic expression of GH
      receptor/binding protein (GHBP) and IGF-I genes in chronic renal failure, mRNA
      levels and the concentrations of its splicing variants were measured by Northern
      Blot in male 5/6 nephrectomized rats (NX, n = 9), aged 26 +/- 1 days, and three
      groups of sham-operated rats: (1) fed ad libitum (SAL, n = 9); (2) pair-fed with
      NX (SPF, n = 7); and (3) pair-fed with NX in terms of protein ingestion but
      calorically supplemented up to the intake of SAL (SPF+, n = 8). NX rats had
      severe renal failure, serum urea nitrogen 106 +/- 11 mg/dl (mean +/- SEM), and
      were growth retarded. GH receptor/GHBP gene expression was detected as two bands
      of 4.7 and 1.2 kb, respectively. The amount of mRNA was lower (P < 0.0001) in NX
      than SAL, either when both bands were considered together or separately. No
      differences were found between NX, SPF, and SPF+. Serum GHBP concentrations were
      higher (P < 0.01) in NX rats than the other groups. For the IGF-I gene, two bands
      of 7.5 and 1.8-0.8 kb were identified. Expression of IGF-I gene was reduced (P <
      0.05) in NX in comparison with SAL, this reduction being more marked for the 7.5
      kb transcript (amount of mRNA equal to 56.6 +/- 2.6 vs 84.8 +/- 6.2% of values
      found in SAL rats). There were no differences between NX and SPF. Normalization
      of caloric intake in SPF+ resulted in partial recovery of the 7.5-kb band and did
      not modify the 1.8-0.8 kb mRNAs. Circulating IGF-I levels were no different among
      the four groups. These data confirm that expression of liver GH receptor/GHBP and
      IGF-I genes is markedly decreased in uremic rats. Nutritional deficiency and not
      uremia itself seems to be the main causal factor, with protein deficit playing a
      major role.

PMID- 10207510
TI  - L-arginine-induced growth hormone secretion is not influenced by co-infusion of
      the nitric oxide synthase inhibitor N-monomethyl-L-arginine in healthy men.
AB  - In animals, it has been demonstrated that nitric oxide (NO) is a potent
      neuroregulatory substance. By intravenous infusion, L-arginine is converted to NO
      and citrulline, but it is unknown whether NO is responsible for the GH
      stimulating effect of L-arginine in humans. We investigated whether intravenous
      infusion of the NO synthase inhibitor N-monomethyl-L-arginine (L-NMMA) influenced
      L-arginine stimulated GH secretion. Ten healthy men, aged 28.6 +/- 1.9 (mean +/-
      SEM) years were examined twice. L-arginine was infused intravenously in a dose of
      0.5 g/kg, max 35 g, from 0 to 30 min, accompanied by either: (1) L-NMMA from -5
      to 0 min, in a dose of 3 mg/kg, max 250 mg, and in a dose of 3.5 mg/kg, max 250
      mg from 0 to 60 min; or (2) a saline infusion. Heart rate increased (P = 0.032),
      and diastolic blood pressure decreased (P < 0.001) in the two situations. Plasma
      cGMP was unchanged and identical in the two situations (P = 0.679). Urine
      cGMP/creatinine ratio increased during both examinations (P = 0.041). Growth
      hormone secretion increased significantly during L-arginine infusion (P = <
      0.001) without any effect of L-NMMA (P = 0.848). We did not find evidence that NO
      influences GH secretion. It remains to be tested, however, whether a higher dose
      of L-NMMA may influence L-arginine stimulated GH secretion.

PMID- 10207511
TI  - Serum free insulin-like growth factor-I is dose-dependently decreased by
      methylprednisolone and related to body weight changes in rats.
AB  - Glucocorticoids usually inhibit growth despite a paradoxical increase in total
      IGF-I. To investigate the effect of methylprednisolone on free IGF-I, rats were
      treated with for 3 days (0, 1, 2, 4, and 6 mg/kg per day). A dose-dependent
      decrease in ultrafiltrated serum free IGF-I was observed, being lowest after 6
      mg/kg (P < 0.001 all groups vs controls). Total IGF-I was increased in the groups
      receiving 2 mg/kg (P < 0.05). Weight change in the 24 h prior to blood sampling
      was positively correlated with free IGF-I (R = 0.46, P = 0.0002), but not with
      total IGF-I. Immunoassayable IGFBP-1 was decreased in rats given 4 mg/kg (P =
      0.001), whereas there was no change in IGFBP-3 or acid-labile subunit. We propose
      that in rats the glucocorticoid-induced weight loss may in part be due to
      suppression of circulating free IGF-I.

PMID- 10207513
TI  - Katherine A. Shaw Division of Public Services and Programs annual report July
      1996-June 1997

PMID- 10207512
TI  - Report of the president of the College of Physicians of Philadelphia, 1997

PMID- 10207514
TI  - Forum on disability and the presidency College of Physicians of Philadelphia,
      November 19, 1997

PMID- 10207515
TI  - When the president is the patient

PMID- 10207517
TI  - Resuscitating the twenty-fifth amendment: mandating a second opinion for the
      determination of presidential disability

PMID- 10207516
TI  - President Lincoln's fatal wound: an experimental study

PMID- 10207518
TI  - The illness and death of President Franklin D. Roosevelt

PMID- 10207519
TI  - Inoculation, patients, and physicians: the transformation of medical practice in
      Philadelphia, 1730-1810

PMID- 10207520
TI  - A nineteenth-century literary physician: S. Weir Mitchell's medical work and
      imaginative writing

PMID- 10207522
TI  - Katherine A. Shaw Division of Public Services and Programs annual report July
      1997-June 1998.

PMID- 10207521
TI  - Report of the president of the College of Physicians of Philadelphia, 1998.

PMID- 10207523
TI  - Library annual report July 1, 1997-June 30, 1998.

PMID- 10207525
TI  - Hippocrates and contemporary medicine.

PMID- 10207527
TI  - "The foul altar of a dissecting table": anatomy, sex, and sensationalist fiction
      in mid-nineteenth-century America.

PMID- 10207526
TI  - "A deep fund of hatred and resentment": clinical encounters in eighteenth-century
      England.

PMID- 10207528
TI  - Charges of unethical conduct made by the Camden County Medical Society against
      Samuel D. Gross, M.D. and Joseph Pancoast, M.D.

PMID- 10207529
TI  - Highly cross-linked networks for dental applications obtained by photocuring of
      tris[2-(acryloyloxy)ethyl]isocyanurate, 2-ethyl-2-(hydroxymethyl)-1,3-propanediol
      triacrylate, and pentaerythritol triacrylate.
AB  - Highly cross-linked networks have been obtained by photoinitiated camphorquinone
      amine polymerization of tris[2-(acryloyloxy)ethyl]isocyanurate alone and/or with
      2-ethyl-2-(hydroxymethyl)-1,3-propanediol triacrylate or pentaerythritol
      triacrylate, which can be considered a new class of dental restorative resins.
      The most effective coinitiators in this system are amines such as ethyl-4
      dimethylaminobenzoate, N,N-dimethyl-benzylamine, and 2,4,6
      tris(dimethylaminomethyl)phenol. The volume shrinkages of polymerized samples
      were 8%-13%. The hardness of photocured resins in the presence of an inorganic
      filler (aluminum/fluoro/silicate glass, Ketac-Fil was slightly less than that of
      a restorative composite material (Z100 MP).

PMID- 10207530
TI  - Congruence between self-reported and actually provided prosthodontic services
      among Swedish dentists.
AB  - The purpose of this study, comprising two parts, was to investigate the
      congruence between answers given by general dentists in questionnaires concerning
      prosthodontic services and the recorded information on the services actually
      performed by each dentist. In Part I it is investigated whether questionnaire
      reports of weekly working hours devoted to prosthodontics can be used as
      indicators of actual prosthodontic production. Part II deals with the dentists'
      self-reported numbers of single crowns, fixed partial dentures (FPDs), and
      removable dentures. These reported services are compared with the services
      actually provided. Part I: A regression analysis indicates a lacking precision
      for the individual dentist, indicated by a relatively low explained variance (R2
      = 0.20). However, a highly significant association is seen between the two
      production measures (P = 0.000). Part II: The congruence between stated and
      actually provided services is higher for single crowns and removable dentures
      than for FPDs. Bivariate regression models are statistically significant for all
      three services. In Part II, the reported weekly working hours used for
      prosthodontics covaries significantly with prosthodontic production, but the
      association is not as strong as in Part I. Although the precision in both Part I
      and Part II is low for the individual dentist, the questionnaire measure is found
      to be useful as an indicator in a population of dentists. It is concluded that
      the questionnaire data can be used as reasonably valid expressions of
      prosthodontic activity in population-oriented analyses among general dentists.

PMID- 10207531
TI  - Synovial fluid sampling from the temporomandibular joint: sample quality criteria
      and levels of interleukin-1 beta and serotonin.
AB  - The aims of this study were to compare two sets of quality criteria (SQC A and B)
      with respect to synovial fluid (SF) sampling and to present temporomandibular
      joint (TMJ) SF levels of IL-1 beta and 5-HT. The study comprised 310 TMJ SF
      samples from 12 healthy individuals (HI) and 59 patients with TMJ inflammatory
      disorders. Ten HI and 37 patients were selected for investigation of TMJ SF
      levels and samples were obtained by a push-and-pull method with quantification by
      vitamin B12. The SQC comprised aspirate weight (AW), dilution factor (DF), blood
      contamination and hemolysis. IL-1 beta and 5-HT levels did not differ between the
      samples that satisfied SQC A or B. The proportion of samples that satisfied SQC A
      was higher than for SQC B. Patients with polyarthritides had significantly higher
      TMJ SF concentrations of 5-HT and IL-1 beta than HL. In conclusion, there is a
      recovery of TMJ SF of 0.1-0.2 g with the method used and the criteria set with
      the highest success rate do not differ from the other one with respect to SF
      levels of IL-1 beta and 5-HT. This set of sample quality criteria comprised no
      hemolysis, no or only minor blood contamination, AW > 0.5 g and DF < 0.98. The
      higher SF levels in the diseased TMJ (polyarthritides) compared to the healthy
      joint with respect to 5-HT and IL-1 beta is of clinical diagnostic relevance and
      the presence of 5-HT or IL-1 beta in TMJ SF seems to indicate a pathological
      joint condition probably of an inflammatory nature.

PMID- 10207532
TI  - Effect of an antibacterial dental varnish on the levels of prostanoids,
      leukotriene B4, and interleukin-1 beta in gingival crevicular fluid.
AB  - The aim of this study was to investigate the effects of a chlorhexidine/thymol
      containing dental varnish on the levels of prostaglandin E2 (PGE2), prostaglandin
      I2 (PGI2), leukotriene B4 (LTB4), and interleukin-1 beta (IL-1 beta) in gingival
      crevicular fluid (GCF). The material consisted of 15 adolescents undergoing
      treatment with fixed orthodontic appliances. Four buccal sites adjacent to bands
      or brackets and exhibiting a mild chronic gingival inflammation were selected in
      the upper quadrants of each patient. According to a split-mouth technique, the
      first and second quadrants were randomly treated with either a varnish (Cervitec)
      containing 1% chlorhexidine diacetate and thymol (CHX/thymol) or a placebo
      varnish without active ingredients. The varnishes were applied immediately after
      the baseline registration, and follow-up examinations were carried out after 3,
      8, and 30 days. GCF was sampled with the aid of a paper strip and the volume was
      determined using a Periotron 8000. The concentrations of PGE2, PGI2, LTB4, and IL
      1 beta in GCF were assessed using radioimmunoassay and ELISA techniques. The
      results unveiled statistically significant reductions of PGE2, PGI2, and LTB4
      levels in GCF following the active varnish treatment when compared to baseline
      values. A slight drop in IL-1 beta levels was registered after both active and
      placebo varnish applications, but the differences were not significant. The
      results suggest that treatment with an antibacterial varnish decreases the levels
      of inflammatory mediators PGE2, PGI2, and LTB4 in gingival crevicular fluid and
      further support the concept that topical application of a CHX/thymol-containing
      varnish is beneficial in patients with chronic gingival inflammation.

PMID- 10207533
TI  - A time-series analysis of caries status among adolescents in relation to
      socioeconomic variables in Goteborg, Sweden.
AB  - The aim of this study was to detect, using time-series analysis methods, whether
      measurable socioeconomic adjustments for the time period 1986-96, as presented by
      caries index values, could be related to a new trend in caries status development
      for specific age groups leaving the free state-organized dental care system. In
      the study, Goteborg was divided into four districts. The study showed a favorable
      development in dental health for the 15-19 age group. However, the caries
      incidence index DSa (decayed approximal surfaces) values showed no or only
      negligible signs of lower mean values. During the study period, the study showed
      an unfavorable trend concerning the socioeconomic variables related to health
      care. However, the incongruity for the different districts between the trend
      results of the caries index values and the contemporaneous socioeconomic variable
      development indicated few signs of relationship. In relation to general
      discussions of environmental questions, the idea of sustainable development was
      discussed when applied to the field of dental care. The results of this study
      indicate that dental health, in times of major economic adjustments and lack of
      resources for health care for the 15-19 age group in Goteborg--as interpreted by
      the caries indices used is an example of sustainable dental health development.

PMID- 10207534
TI  - Durability of tunnel restorations in general practice: a three-year multicenter
      study.
AB  - Twelve dentists, clinically experienced and familiar with the tunnel technique,
      placed 374 tunnel restorations in permanent teeth. Mean age of the patients was
      19.1 years (range 10-74). The filling material used was a glass cermet cement,
      Ketac Silver. After 1, 2 and 3 years the teeth were controlled by the dentists.
      The bitewing radiographs from baseline, 1, 2 and 3 years were also analyzed by 2
      of the authors, independently. The baseline radiographs showed technical defects
      in 6% and indicated remaining dentin caries in 8% of the restorations. After 3
      years, 305 restorations were accessible for examination. The cumulative
      replacement rate was 20%. The main reasons for replacement were marginal ridge
      fracture (14%) and dentin caries (3%). The number of restorations showing
      untreated progressive caries increased during the study. After 3 years, untreated
      dentin caries was seen in 28 cases (11%) and almost half of the left enamel
      lesions showed progression.

PMID- 10207535
TI  - Benzydamine reduces prostaglandin production in human gingival fibroblasts
      challenged with interleukin-1 beta or tumor necrosis factor alpha.
AB  - Benzydamine [1-benzyl-3-(3-dimethylamino)propoxy-1H-indazole] is a drug with
      analgesic, anesthetic, antimicrobial and anti-inflammatory activity. The purpose
      of the present study was to investigate the effect of benzydamine on
      prostaglandin production in human gingival fibroblasts. Benzydamine significantly
      reduced the basal production of both prostaglandin E2 (PGE2) and 6-keto-PGF1
      alpha, the stable breakdown product of prostaglandin I2 (PGI2), in unstimulated
      human gingival fibroblasts. When the cells were treated simultaneously with
      benzydamine and the cytokines IL-1 beta or TNF alpha, the agent benzydamine
      reduced (P < 0.05) the stimulatory effect of IL-1 beta and TNF alpha
      respectively, on PGE2 and PGI2 production in human gingival fibroblasts.
      Furthermore, benzydamine reduced (P < 0.05) both the basal level and the cytokine
      induced 3H-arachidonic acid release 3H-(AA) in gingival fibroblasts. The addition
      of exogenous arachidonic acid to the cells resulted in enhanced PGE2 production,
      which was reduced (P < 0.05) in the presence of benzydamine. The study indicates
      that benzydamine reduces the prostaglandin synthesis in gingival fibroblasts,
      partly at the level of phospholipase A2, by diminishing the liberation of
      arachidonic acid (AA) from phospholipids, and partly at the level of
      cyclooxygenase. The inhibitory effect of benzydamine on prostaglandin production
      may explain the anti-inflammatory effect of the drug in the management of
      patients with oral inflammatory conditions.

PMID- 10207536
TI  - Perceived control systems, work conditions, and efficiency among Swedish
      dentists: interaction between two sides of human resource management.
AB  - Two aspects of Human Resource Management (HRM), a main trend in modern personnel
      management, are considered in this study: A 'hard' version stressing performance
      monitoring and competition, and a 'soft' version stressing communication with
      employees. The aim of the investigation was to examine whether these two aspects
      of modern management are reflected in dentists' perceptions of differences in
      work conditions compared with other professionals. A questionnaire was answered
      by 312 publicly employed dentists and 3,600 other professionals in Sweden. The
      response rate was 66-77%. Effects from HRM on work, conditions and perceived
      efficiency were confirmed. The interaction effects, reflecting the duality of
      HRM, resulted in poorer work conditions, e.g. worse balance between effort and
      reward and worse opportunities for developing competence and collaboration in the
      workplace. This pertains especially in the case of dentists, where the positive
      effects of 'soft' HRM did not compensate for the negative effects of 'hard' HRM.
      Dentists in Sweden's Public Dental Health Service appear as a vulnerable group
      among Swedish professionals.

PMID- 10207537
TI  - Incidence of, and reasons for, tooth mortality among mentally retarded adults
      during a 10-year period.
AB  - The aim of the study was to investigate the reasons for, and incidence of, tooth
      mortality over a 10-year period in mentally retarded adults receiving regular
      dental care. The number of teeth present in 115 individuals (mean age in 1984 was
      41.0, range 19-83 years) was registered in 1984 and 1994. The reasons for tooth
      mortality, medication utilization, frequency of dental care visits and
      cooperation during dental treatment were registered and related to tooth loss.
      The average incidence of tooth mortality was 3.72 teeth during the 10-year
      period. The mean number of dental care visits per year was 6.6. Most of the 428
      teeth (58%) were lost due to periodontal disease. The preventive dental care
      given was not sufficient to arrest oral diseases. The data indicate, however,
      that achievement of cooperation in dental care situations not only makes dental
      treatment possible, but also leads to a decreased incidence of tooth mortality.

PMID- 10207538
TI  - Protease inhibitor-containing regimens compared with nucleoside analogues alone
      in the suppression of persistent HIV-1 replication in lymphoid tissue.
AB  - OBJECTIVE: Lymphoid tissue provides a reservoir where HIV can persist. However,
      therapies incorporating a protease inhibitor can target this reservoir. This
      study was designed to investigate the relative long-term effects on lymph-node
      viral load and cellular architecture of regimens containing multiple nucleosides
      alone or in combination with protease inhibitors. METHODS: Axillary lymph-node
      biopsies from 12 patients with undetectable viraemia (viral load < 20 copies/ml:
      mean CD4 cells 525 x 10(6)/l) for a mean period of 25 months (range, 10-52
      months) were investigated for the presence of HIV by in situ hybridization and
      coculture. Four patients were receiving multiple nucleoside analogues alone or in
      one case with a suboptimally dosed protease inhibitor (group I). Protease
      inhibitor was added to the regimen of seven patients at least 6 months prior to
      lymph-node biopsy (group II). Standard flow cytometry and virological data were
      obtained from peripheral blood every 3 months. RESULTS: By in situ hybridization,
      more productively infected CD4+ T cells were found in the lymph nodes of group I
      patients treated with nucleoside analogues alone. Very low numbers of
      productively infected lymph node cells were detected in the protease inhibitor
      treated group II. No trapping of virions on the follicular dendritic cell (FDC)
      network was detectable in protease inhibitor-treated patients. In contrast, large
      deposits of FDC-bound virions were observed in three out of five patients from
      group I. Virus cultures from lymph node cells were positive in these three group
      I patients compared with only one out of seven patients from group II. Sequencing
      reverse transcriptase and protease genes from these isolates revealed typical
      mutations conferring resistance to the previously administered nucleoside
      analogue. A more preserved lymph node architecture and less signs of
      immunopathological change were also observed in protease inhibitor-treated
      patients. CONCLUSIONS: Undetectable plasma viraemia using the ultrasensitive PCR
      assay for prolonged periods of time does not always reflect complete HIV-1
      suppression within the lymphoid compartment. Our results suggest that protease
      inhibitor-containing regimens target HIV reservoirs in lymphoid tissue more
      effectively and preserve or restore lymph node architecture.

PMID- 10207540
TI  - Astrocytes: HIV cellular reservoirs and important participants in
      neuropathogenesis.

PMID- 10207539
TI  - Combination therapy containing ritonavir plus saquinavir has superior short-term
      antiretroviral efficacy: a randomized trial.
AB  - OBJECTIVES: To compare the efficacy and safety of indinavir 800 mg three times a
      day, ritonavir 600 mg twice a day, and a combination of ritonavir 400 mg twice a
      day and saquinavir 400 mg twice a day, when administered with two nucleoside
      analogues. DESIGN: A randomized, open-labelled, controlled trial. Two hundred and
      eighty-four patients started randomized treatment. The primary end-point was the
      proportion of patients with HIV RNA of 200 copies/ml or less (Roche Amplicor) and
      HIV RNA of 20 copies/ml or less (Roche ultradirect assay) at 6 months. Analysis
      was performed as intent-to-treat, and missing values were accounted for as
      failures. RESULTS: As of 1 May 1998, 269 patients should have completed 24 weeks
      of treatment. The proportion of patients with HIV RNA of 200 copies/ml or less
      was 71% (indinavir), 67% (ritonavir), and 82% (ritonavir + saquinavir), P = 0.07.
      In antiretroviral drug-naive patients (n = 119), the corresponding figures were
      63, 57, and 89% (P < 0.01), whereas among drug-experienced patients (n = 165) 77,
      74, and 77% had HIV RNA of 200 copies/ml or less (P = 0.90). The same pattern was
      observed in the ultradirect analysis. All three regimens were generally safe, but
      significantly more patients in the ritonavir group (37%) stopped treatment
      because of adverse drug reactions compared with the indinavir group (8%) and the
      ritonavir plus saquinavir group (16%) (P < 0.001). CONCLUSIONS: Treatment with
      saquinavir plus ritonavir in combination with two nucleoside analogues is
      generally safe, and has superior short-term antiviral efficacy compared with
      indinavir and ritonavir also combined with two nucleoside analogues in
      antiretroviral drug-naive patients. Further follow-up is needed to determine the
      durability of the viral response.

PMID- 10207541
TI  - HIV-1-specific mucosal IgA in a cohort of HIV-1-resistant Kenyan sex workers.
AB  - OBJECTIVES: Most HIV-1 transmission is sexual; therefore, immune responses in the
      genital mucosa may be important in mediating protection against HIV infection.
      This study examined HIV-1-specific mucosal IgA in a cohort of HIV-1-resistant
      Kenyan female sex workers. METHODS: HIV-1-specific immune responses were compared
      in HIV-1-resistant and HIV-1-infected sex workers, and in lower risk uninfected
      women. Cervical and vaginal samples from each group were tested for HIV-1
      specific IgA and IgG by enzyme immunoassay. Systemic T-helper lymphocyte cell
      responses to HIV-1 envelope peptide epitopes were assayed using an interleukin 2
      bioassay. HIV-1 risk-taking behaviours were assessed using standardized
      questionnaires. RESULTS: HIV-1-specific IgA was present in the genital tract of
      16 out of 21 (76%) HIV-1-resistant sex workers, five out of 19 (26%) infected
      women, and three out of 28 (11%) lower risk women (P < 0.0001). Among lower risk
      women, the presence of HIV-1-specific IgA was associated with HIV-1 risk-taking
      behaviour. Systemic T-helper lymphocyte responses to HIV-1 envelope peptides were
      present in 11 out of 20 (55%) HIV-1-resistant women, four out of 18 (22%)
      infected women, and one out of 25 (4%) lower risk women (P < 0.001). T-helper
      lymphocyte responses did not correlate with the presence or titre of virus
      specific mucosal IgA in any study group. CONCLUSIONS: HIV-1-specific IgA is
      present in the genital tract of most HIV-1-resistant Kenyan sex workers, and of a
      minority of lower risk uninfected women, where it is associated with risk-taking
      behaviour. These data suggest a role for mucosal HIV-1-specific IgA responses in
      HIV-1 resistance, independent of host cellular responses.

PMID- 10207542
TI  - Serum HIV-1 p24 antibody, HIV-1 RNA copy number and CD4 lymphocyte percentage are
      independently associated with risk of mortality in HIV-1-infected children.
      National Institute of Child Health and Human Development Intravenous
      Immunoglobulin Clinical Trial Study Group.
AB  - OBJECTIVE: The role of HIV-1 antibody in modulating disease progression must be
      assessed in the context of other immune and viral load markers. We evaluated the
      association between HIV-1 p24 antibody, HIV-1 RNA, immune complex-dissociated
      (ICD) p24 antigen, CD4 cell percentage, and mortality in a cohort of 218 HIV
      infected children enrolled in a trial of intravenous immunoglobulin prophylaxis
      of bacterial infections. METHODS: CD4 cell percentage was measured and sera
      collected and stored at baseline and every 3 months on study (1988-1991). Stored
      sera were assayed for HIV-1 p24 antibody, HIV-1 RNA, and ICD p24 antigen.
      Mortality was recorded during the trial and updated through 1996 (mean total
      follow-up, 6.3 years). RESULTS: Eighty-one (37%) children died; probability of
      mortality for children with baseline HIV-1 p24 antibody concentrations of
      undetectable (< 1), 1-4, 5-124, and > or = 125 reciprocal titer units (RTU) was
      61, 50, 24, and 10%, respectively. A 3.5-fold increase in the relative risk (RR)
      of death [95% confidence interval (CI), 2.2-5.5] was observed among children with
      baseline HIV-1 p24 antibody concentration < 5 RTU compared with > or = 5 RTU. In
      multivariate analyses, p24 antibody, HIV-1 RNA, and CD4 cell percentage but not
      ICD p24 antigen were independently associated with mortality; the RR of death
      increased by 1.7 (95% CI, 1.3-2.1) for each log10 decrement in baseline HIV-1 p24
      antibody. CONCLUSIONS: HIV-1 p24 antibody, HIV-1 RNA and CD4 cell percentage
      independently predict mortality amongst infected children. Whereas CD4 cell
      percentage provides an estimate of the general degree of immune suppression, HIV
      1 p24 antibody could provide an easily obtained, inexpensive assessment of CD4
      cell function and could augment prognostic information provided by CD4 cell count
      and viral load for clinical management of infected children.

PMID- 10207543
TI  - Interpatient genetic variability of HIV-1 group O.
AB  - OBJECTIVE: To analyse the genetic and phylogenetic characteristics of HIV-1 group
      O viruses. MATERIALS AND METHODS: The env gene, encoding the gp160 glycoprotein,
      and a partial p24-encoding gag gene fragment of a Cameroonian (CA9) and a
      Gabonese (VI686) HIV-1 group O virus, isolated from cultured peripheral blood
      mononuclear cells of symptomatic patients, were sequenced, aligned with other
      representatives of group O for which the same region has been documented, and
      genetically and phylogenetically analysed. RESULTS: Phylogenetic analysis of the
      env gene (gp160) revealed that CA9, VI686, ANT70, and four Ha strains formed a
      separate cluster, which was supported by 100% of all bootstrap trees. In
      addition, these seven isolates were part of the same clade in the p24 phylogeny.
      VAU and MVP5180 may represent two other subtypes. CONCLUSION: We have
      characterized two group O viruses, originating from Cameroon and Gabon, which
      show a close evolutionary relationship to ANT70 and four Ha strains based on the
      entire env gene, suggestive of a first group O subgroup, tentatively named the
      HIV-1 group O env ANT70 clade or subtype.

PMID- 10207544
TI  - Granulocyte-macrophage colony-stimulating factor and fluconazole enhance anti
      cryptococcal activity of monocytes from AIDS patients.
AB  - OBJECTIVE: To investigate the effect of human recombinant granulocyte-macrophage
      colony-stimulating factor (hrGM-CSF) and fluconazole on anti-cryptococcal
      activity of monocytes from AIDS patients and normal subjects. DESIGN: The effect
      of GM-CSF and fluconazole on fungistatic and fungicidal activity of monocytes was
      studied in an in vitro system. METHODS: Monocytes were treated in vitro with hrGM
      CSF and fluconazole or either agent alone for 24 or 48 h, and fungistatic and
      fungicidal activity was evaluated in a colony-forming unit inhibition assay.
      CD11b/CD18 expression in monocytes was measured by flow cytometry analysis.
      Superoxide anion generation by peripheral blood monocytes was measured in the
      presence of pre-opsonized zymosan. RESULTS: Defective antifungal capacity of
      monocytes from AIDS patients was observed. GM-CSF treatment of monocytes from
      AIDS patients increased fungistatic activity, and the combination of hrGM-CSF and
      fluconazole resulted in fungicidal activity. The mechanisms involved in the GM
      CSF-mediated effect appeared to be mediated by (i) enhancement of phagocytic
      activity, (ii) increase of superoxide anion generation, and (iii) upregulation of
      CD11b/CD18 expression on the monocyte surface. CONCLUSIONS: Our data highlight
      the effect of GM-CSF on anti-cryptococcal activity of human monocytes and show a
      synergistic effect of GM-CSF with fluconazole, suggesting a new therapeutic
      strategy in the treatment of cryptococcosis.

PMID- 10207545
TI  - HIV-1 RNA response to antiretroviral treatment in 1280 participants in the Delta
      Trial: an extended virology study.
AB  - OBJECTIVE: To assess changes in HIV RNA and their relationship to disease
      progression. DESIGN AND SETTING: Delta was a randomized double-blind trial
      comparing zidovudine (ZDV) monotherapy with ZDV plus didanosine (ddI) or ZDV plus
      zalcitabine (ddC). Participants had AIDS (with CD4 cell counts above 50 x
      10(6)/l), AIDS-related complex, or were asymptomatic with CD4 cell counts below
      350 x 10(6)/l. The trial included both ZDV-naive and ZDV-experienced
      participants. PARTICIPANTS: A total of 1280 participants in the Delta trial whose
      serum samples had been stored at -70 degrees C and who had a minimum of one
      sample taken before the start of treatment and at least one later sample.
      METHODS: HIV-1 RNA quantification was performed using the nucleic acid sequence
      based amplification HIV-1 RNA quantitative assay with a cut-off of 800 copies/ml.
      RESULTS: Reductions in HIV RNA by treatment group were consistent with the
      clinical results; in ZDV-naive participants the maximum median fall occurred at 4
      weeks for all three groups (ZDV, 0.54 log10 copies/ml; ZDV-ddI, 1.38 log10
      copies/ml; ZDV-ddC, 1.31 log10 copies/ml). On average the reductions were smaller
      in ZDV-experienced participants but the difference between the monotherapy and
      combination arms was very similar in ZDV-naive and experienced participants.
      Baseline HIV RNA levels, adjusted for CD4 cell counts were highly predictive of
      time to virological response (HIV RNA < 800 copies/ml); HIV RNA nadirs achieved
      were predictive of survival. Viral load rebound following response was
      independent of treatment group and previous ZDV therapy. CONCLUSIONS: Virological
      changes in response to treatment are of value in assessing prognosis and the
      activity of new therapies; in particular, there is a strong association between
      the minimum HIV RNA achieved in the first 16 weeks and subsequent clinical
      response. CD4 cell counts are independently predictive of response.

PMID- 10207546
TI  - In vivo HIV-1 replicative capacity in early and advanced infection.
AB  - OBJECTIVE: Previous studies on patients treated with potent antiretroviral
      therapy have shown that viral clearance rates do not tend to change between early
      and advanced HIV-1 infection. Our objective was to investigate whether the other
      major aspect of virus dynamics, viral replicative capacity, does change. In vitro
      work has indicated that the viral replicative, capacity increases but in vivo
      evidence has been lacking. METHODS: As an in vivo measure of the viral
      replicative capacity, we studied the rate of rebound of plasma HIV RNA level
      during a 1-week therapy interruption in previously untreated patients who had
      received 2 weeks of antiretroviral therapy. RESULTS: Such therapy in five
      previously drug-naive patients with high CD4 lymphocyte counts (mean, 611 x
      10(6)/l) and five patients with low counts (mean, 49 x 10(6)/l) led to a mean 2.2
      log10 copies/ml decrease in plasma HIV-1 levels (from 5-6 log10 copies/ml) in 2
      weeks. This was similar in the two groups. Interruption of therapy for the
      ensuing week resulted in a stable HIV-1 level for approximately 2 days followed
      by a rebound towards pretherapy level, which was much more marked in the patients
      with low CD4 cell counts (estimated mean rise 2.22 log10 versus 1.06 log10
      copies/ml; P < 0.02). After restarting therapy, HIV RNA levels returned to pre
      interruption levels. CONCLUSIONS: These findings need confirmation, but the
      ability of HIV-1 to replicate in vivo appears to increase during HIV-1 infection.
      This increased replicative capacity, for which there are several potential
      explanations, may be the cause of gradual CD4 lymphocyte depletion.

PMID- 10207547
TI  - Insertion of two amino acids combined with changes in reverse transcriptase
      containing tyrosine-215 of HIV-1 resistant to multiple nucleoside analogs.
AB  - OBJECTIVE: To identify genotypic drug resistance patterns of HIV-1 in patients
      who were extensively pretreated with anti-HIV drugs and not responding to their
      current antiretroviral combination therapy. METHODS: Drug susceptibility of the
      viruses was tested by a phenotypic recombinant virus assay. Genotypic analysis of
      HIV resistance was performed by sequencing of the amino-terminal part of the
      corresponding reverse transcriptase (RT) gene (amino acids 1-280) for serum
      derived and recombinant viruses. RESULTS: Among viruses from 92 patients studied,
      three (3%) viruses contained a T215Y amino-acid change as well as a previously
      unseen combination of an amino-acid change at codon 67 (N-->E/S) and a two amino
      acid insertion between codons 68 and 69 of the RT gene of HIV-1. Phenotypic
      resistance analysis showed high levels of resistance to zidovudine, lamivudine
      and stavudine (in all patients) and moderate levels of resistance to didanosine
      and zalcitabine (in two patients), whereas neither serum-derived nor recombinant
      viruses contained previously known amino-acid changes conferring resistance to
      didanosine, zalcitabine, lamivudine and stavudine. However, all recombinant
      viruses contained an insertion of two amino acids between codons 68 and 69 of RT
      as well as an amino-acid change at codon 67, as was seen in the serum-derived
      viruses. CONCLUSIONS: Antiretroviral therapy including zidovudine may yield
      replicating viruses with a two amino-acid insertion in RT in combination with
      amino-acid changes at codons 67 and 215, which are highly resistant to lamivudine
      and stavudine on top of zidovudine and have unpredictable susceptibility to
      didanosine and zalcitabine despite lack of previously reported corresponding
      resistance-associated amino-acid changes. It is currently unknown what regimens
      can induce the emergence of this type of multidrug-resistant viruses. This will
      only be elucidated when resistance assays are capable of detecting these mutants.

PMID- 10207548
TI  - Combination antiretroviral therapy including ritonavir in children infected with
      human immunodeficiency.
AB  - OBJECTIVE: To assess the efficacy of combination therapy that includes ritonavir
      in HIV-1 infected children. DESIGN: A monocentric retrospective study. PATIENTS
      AND METHODS: Twenty-two children with a minimum follow-up of 6 months under
      triple therapy including ritonavir were analysed for treatment efficacy. At
      entry, all the patients were protease inhibitor naive and all but two had
      received previous antiretroviral therapy during a median period of 5 years. Their
      initial median CD4+ lymphocyte count and viral load were 121 x 10(6)/l and 5.08
      log10 copies/ml, respectively. Clinical and biological evaluation included
      clinical assessment every 6 weeks and determination of CD4 cell count and HIV-RNA
      concentration every 3 months. RESULTS: Median length of follow-up on triple
      therapy was 15 months (range: 7-21 months). Neither progression in the CDC
      classification nor death occurred. No significant change in mean weight SD scores
      was noted when baseline values were compared with values obtained after 1 year of
      triple therapy. Median CD4 count increases were of 210 x 10(6)/l, 415 x 10(6)/l,
      and 472 x 10(6)/l cells at 6, 12, and 18 months, respectively. Among the patients
      baseline characteristics, neither age nor initial CD4 cells count influenced the
      magnitude of immunologic improvement. There were median decreases of 1.14, 0.95,
      and 1.5 log10 per ml of plasma in the concentration of viral RNA at 6, 12, and 18
      months respectively. Seven patients maintained an undetectable viral load when
      under treatment. The introduction of at least one new reverse transcriptase
      inhibitor at the initiation of triple therapy correlated significantly with a
      greater viral suppression. CONCLUSION: Despite variable viral response,
      antiretroviral-experienced HIV-infected children demonstrated a substantial CD4
      cell increase during a median period of 15 months of ritonavir containing
      combination therapy.

PMID- 10207549
TI  - Persistently negative HIV-1 antibody enzyme immunoassay screening results for
      patients with HIV-1 infection and AIDS: serologic, clinical, and virologic
      results. Seronegative AIDS Clinical Study Group.
AB  - OBJECTIVE: To describe persons with HIV infection and AIDS but with persistently
      negative HIV antibody enzyme immunoassay (EIA) results. DESIGN: Surveillance for
      persons meeting a case definition for HIV-1-seronegative AIDS. SETTING: United
      States and Canada. PATIENTS: A total of eight patients with seronegative AIDS
      identified from July 1995 through September 1997. MAIN OUTCOME MEASURES: Clinical
      history of HIV disease, history of HIV test results, and CD4 cell counts from
      medical record review; results of testing with a panel of EIA for antibodies to
      HIV-1, and HIV-1 p24 antigen; and viral subtype. RESULTS: Negative HIV EIA
      results occurred at CD4 cell counts of 0-230 x 10(6)/l, and at HIV RNA
      concentrations of 105,000-7,943,000 copies/ml. Using a panel of HIV EIA on sera
      from three patients, none of the HIV EIA detected infection with HIV-1, and
      signal-to-cut-off ratios were < or = 0.8 or all test kits evaluated. Sera from
      five patients showed weak reactivity in some HIV EIA, but were non-reactive in
      other HIV EIA. All patients were infected with HIV-1 subtype B. CONCLUSIONS:
      Rarely, results of EIA tests for antibodies to HIV-1 may be persistently negative
      in some HIV-1 subtype B-infected persons with AIDS. Physicians treating patients
      with illnesses or CD4 cell counts suggestive of HIV infection, but for whom
      results of HIV EIA are negative, should consider p24 antigen, nucleic acid
      amplification, or viral culture testing to document the presence of HIV.

PMID- 10207550
TI  - Protease inhibitors as initial therapy for individuals with an intermediate risk
      of HIV disease progression: is more necessarily better?
AB  - OBJECTIVE: To compare three possible therapeutic strategies for the treatment of
      patients with an intermediate risk of HIV disease progression. DESIGN:
      Mathematical modeling based on assumptions derived from published data. METHODS:
      A parametric survival model was fitted to empirical data to describe the survival
      trajectory of untreated individuals. It was assumed that successful treatment
      decreases the risk of disease progression curing the first year after its
      introduction by a constant that is dependent on the magnitude of the initial drop
      in HIV viral load. Thereafter, individual members of the treatment cohort follow
      different pathways, depending on the duration of the initial response or, in case
      of virologic failure, the response to a new drug regimen. RESULTS: Sub-groups of
      patients starting therapy with two nucleoside reverse transcriptase inhibitors
      (NRTI) or two NRTI and a protease inhibitor had the highest instantaneous risk of
      disease progression at the end of the 5-year follow-up period. Patients who
      started therapy with two NRTI and a non-NRTI had the lowest likelihood of
      progression to AIDS or death at 5 years of follow-up. This is because, in the
      case of the subgroup whose initial treatment included a protease inhibitor,
      failure rates due to non-adherence to therapy are high and response to salvage
      therapy is limited by past protease inhibitor experience. CONCLUSIONS: Despite
      the superior virologic potency of the protease inhibitor-containing regimens, in
      this analysis other strategies performed equally well or even better. In the
      absence of solid empirical data and until the advent of antiretroviral regimens
      that are shown to be safe, simple to take, and maximally suppress viral load,
      caution may be required in selecting the long-term therapy for patients with less
      advanced HIV disease.

PMID- 10207551
TI  - New therapy explains the fall in AIDS incidence with a substantial rise in number
      of persons on treatment expected.
AB  - BACKGROUND: A marked decline in the number of reported AIDS cases has been
      observed in the United Kingdom, as in many industrialized countries, in 1996 and
      1997. In England and Wales, a large reduction in AIDS cases has been recorded
      among homosexual and bisexual men. OBJECTIVES: To investigate, using data from
      the homosexuals and bisexuals in England and Wales as an example, possible
      explanations for the above decline such as the effects of new anti-retroviral
      therapies, or a decrease in the incidence of HIV in recent years. METHODS: A
      multistage model of HIV infection, HIV diagnosis, treatment and of AIDS diagnosis
      has been used to represent the pattern of HIV and AIDS incidence in homosexual
      and bisexual men in England and Wales up to the end of 1995. Scenarios for the
      post-1995 period were examined under different assumptions about changes in HIV
      incidence in recent years and treatment uptake and efficacy. RESULTS: The fall in
      the incidence of AIDS is unlikely to be the result of a reduction in HIV
      transmission during the 1990s. The most plausible explanation for this fall is
      the effect of new, more effective, anti-retroviral therapies. As a consequence,
      the number of individuals on treatment is likely to increase by 50 to 100%
      compared with the pre-1996 levels by the year 2001. Also, if the effect of the
      new therapies has a limited duration, or the use of such therapies is not well
      tolerated, the incidence of AIDS will rise again in the near future. CONCLUSIONS:
      These findings indicate that a substantial workload increase is under way for the
      healthcare system, and reiterate the need for measures to reduce HIV transmission
      as a means of bringing about a sustainable change in the incidence of AIDS.

PMID- 10207553
TI  - Is zidovudine therapy in pregnant HIV-infected women associated with gestational
      age and birthweight?
AB  - OBJECTIVE: Prophylactic zidovudine during pregnancy and labour reduces maternal
      viral load and, with neonatal therapy, has been shown to reduce vertical
      transmission. However, zidovudine may have additional effects. Advanced HIV
      disease is associated with premature delivery, which in turn results in increased
      vertical transmission. Data from the European Collaborative Study (ECS) were
      analysed to investigate whether zidovudine could be associated with decreased
      prematurity risk and/or with a reduced frequency of low birthweight. METHODS: HIV
      infected pregnant women enrolled in the ECS were followed prospectively according
      to a standard protocol. Gestational age was assessed by ultrasound, prematurity
      was defined as delivery before 37 weeks and the cut-off for low birthweight was
      2500 g. We calculated odds ratios (OR) to estimate the effect of zidovudine on
      the risk of premature of low birthweight delivery. RESULTS: In 2299 mothers,
      zidovudine taken to reduce the risk of vertical transmission decreased the odds
      of premature delivery by a quarter (OR = 0.76, 95% confidence interval (CI) 0.53
      1.09), and the odds of low birthweight by nearly half (OR = 0.55, 95% CI 0.39
      0.79). Allowing for CD4 count and mode of delivery did not greatly alter these OR
      values. A multivariate analysis suggested that prophylactic zidovudine and
      prematurity were independently associated with risk of transmission. CONCLUSION:
      Our findings suggest an additional health benefit of zidovudine. Even if most
      vertical transmission occurs around the time of delivery, therapy earlier in
      pregnancy could have an indirect effect on transmission rates through delaying
      delivery. This hypothesis needs to be confirmed or refuted by more appropriate
      studies.

PMID- 10207552
TI  - Evaluation of HIV serial and parallel serologic testing algorithms in Abidjan,
      Cote d'Ivoire.
AB  - OBJECTIVE: To evaluate HIV serologic testing algorithms based on a combination of
      three enzyme linked immunosorbent assays (ELISA) for the confirmation of HIV
      infection in Abidjan, Cote d'Ivoire, where HIV-2 and HIV-1 non-B subtypes are
      prevalent. METHODS: A total of 1069 human sera with known serologic status, in
      addition to a seroconversion and low titer antibody panel were initially tested
      by six ELISA to determine the sensitivity, specificity and delta values of the
      assays. On the basis of the performance of the assays, three ELISA (Enzygnost,
      ICE 1.0.2, and Vironostika) were selected for use in a parallel and serial
      testing algorithm in analyzing 8283 consecutively collected sera. In the parallel
      testing algorithm, sera concordantly reactive or non-reactive by Enzygnost and
      ICE 1.0.2 were considered as true positive or true negative, respectively. In the
      serial algorithm, sera reactive by Enzygnost were retested by ICE 1.0.2. Sera
      with discordant results were tested by Vironostika, and the results was
      considered definitive. All reactive sera, plus a random sample of negative sera
      were tested for confirmation by Peptilav. In addition, a random sample of
      reactive sera was tested by Western blot. RESULTS: All ELISA had 100%
      sensitivity; specificities ranged from 96.8 to 100%. Positive and negative delta
      values of the ELISA were high (range, 6.89 to 46.07 and -2.05 to -5.75,
      respectively). Of the 8283 sera, 2054 were considered true positives and were
      correctly classified by the parallel testing algorithm (sensitivity, 100%). Of
      the 6229 true negative sera, 6226 were negative by the parallel testing algorithm
      (specificity, 99.95%). The sensitivity of the serial algorithm was 99.96%, and
      specificity was 99.95%. None of the 250 concordant ELISA-negative sera in the
      algorithm that were randomly tested in Peptilav was positive; similarly, all of
      the 103 concordant ELISA-positive sera were confirmed by Western blot. The three
      ELISA algorithm resulted in reagent cost-savings of at least 50% compared with
      the Peptilav-based algorithm. CONCLUSION: These results suggest that a
      combination of ELISA using different principles or antigens in a serial or
      parallel algorithm is an efficient and cost-effective alternative to the standard
      algorithm in areas where HIV-1 and HIV-2 are prevalent.

PMID- 10207554
TI  - Post-partum sexual abstinence in West Africa: implications for AIDS-control and
      family planning programmes.
AB  - OBJECTIVE: To assess whether the custom of prolonged post-partum sexual
      abstinence in Benin is associated with an increased incidence of extra-marital
      sexual contacts by husbands. DESIGN: Cross-sectional survey of adult men and
      women. METHODS: Data obtained from men on their extra-marital sexual behaviour in
      the past 12 months were linked to data on post-partum abstinence over the same
      time interval reported by wives. Multivariate analysis was applied to assess the
      association between conjugal abstinence and husband's extra-marital sex, net of
      the effects of possible confounders. RESULTS: Approximately half of married men
      experienced post-partum abstinence in the past 12 months. In this group, 32%
      reported one or more extra-marital sexual contacts compared with 20% among those
      who experienced no abstinence (OR = 1.8, P < 0.001). This association is
      essentially unchanged after controlling for marriage type, age, education, urban
      rural residence, income and household wealth. Age, income and wealth are also
      significant predictors of the probability of extra-marital sex. The effects of
      income and wealth largely disappear when attention is restricted to extra-marital
      sex without using a condom on the most recent occasion. CONCLUSIONS: The
      potentially protective effect of prolonged abstinence after childbirth in Benin
      (and probably in much of West Africa) is offset by an increased probability that
      husbands will seek extra-marital partners without using condoms. Although not
      quantifiable, the enhanced longer-term risks of sexually transmitted diseases/HIV
      infection for wives probably outweigh the short-term benefits. Family planning
      practitioners in this region should not hesitate to recommended the early
      resumption of sex and suitable methods of post-partum contraception for women who
      express concern or uncertainty about their husband's behaviour.

PMID- 10207555
TI  - Serological testing algorithms for the diagnosis of HIV infection.

PMID- 10207556
TI  - Vaccination and HIV-1 replication during highly active antiretroviral therapy.

PMID- 10207558
TI  - Molecular typing of non-typhoid Salmonella strains isolated from HIV-infected
      patients with recurrent salmonellosis.

PMID- 10207557
TI  - The decline of CD8+CD28+ peripheral lymphocytes is correlated with the evolution
      of AIDS in macaques infected with SIVmac251.

PMID- 10207559
TI  - Cerebrospinal fluid S-100b concentrations in patients with HIV infection.

PMID- 10207560
TI  - Recombinant interleukin-2 for treatment of HIV reduces hepatitis C viral load in
      coinfected patients.

PMID- 10207561
TI  - The prevalence of non-B subtype HIV-1 in a London HIV/AIDS outpatient clinic.

PMID- 10207562
TI  - Incidence of HIV infection in homosexual men attending a sexually transmitted
      disease clinic in London measured by a novel unlinked anonymous method.

PMID- 10207564
TI  - HIV/AIDS, orphans, and access to school education in a community of Kampala,
      Uganda.

PMID- 10207565
TI  - Withdrawal of Mycobacterium avium complex suppressive therapy in HIV-1-infected
      patients on highly active antiretroviral therapy.

PMID- 10207563
TI  - Child feeding practices of HIV-positive mothers in Cape Town, South Africa.

PMID- 10207566
TI  - Indinavir and thrombocytopenia.

PMID- 10207567
TI  - Tuberculosis treatment practices in the era of protease inhibitors: a provider
      survey.

PMID- 10207568
TI  - Involvement of human interleukin-6 in systemic manifestations of human
      herpesvirus type 8-associated multicentric Castleman's disease.

PMID- 10207569
TI  - Visceral leishmaniasis in HIV-infected patients with non-detectable HIV-1 viral
      load after highly active antiretroviral therapy.

PMID- 10207570
TI  - State medical peer review: high cost but no benefit--is it time for a change?

PMID- 10207571
TI  - Medicare+Choice appeal procedures: reconciling due process rights and cost
      containment.

PMID- 10207572
TI  - Sex offenders, mental illness and criminal responsibility: the constitutional
      boundaries of civil commitment after Kansas v. Hendricks.

PMID- 10207573
TI  - Direct-to-consumer prescription drug advertising.

PMID- 10207574
TI  - Body-rocking and other habits of college students and persons with mental
      retardation.
AB  - Prevalence of body-rocking in college students was assessed, and the
      characteristics of body-rocking of college students were compared to those of
      individuals with mental retardation. For college students, the prevalence
      depended on the restrictiveness of the method used and varied between 3% and 25%.
      Video samples showed that when compared with college students, a greater
      proportion of people with mental retardation engage in body-rocking, seem less
      sensitive to situational factors, demonstrate atypical collateral behaviors,
      engage in less leg-kicking, and execute their body-rocking with larger
      amplitudes. There were no differences in duration or number of individual rocks
      or bouts of body-rocking. We conclude that body-rocking is a "normal" behavior
      whose form of expression may become atypical.

PMID- 10207575
TI  - Child care and employment in relation to infants' disabilities and risk factors.
AB  - The impact of disability- and risk-related characteristics of 166 infants on
      their mothers' employment and child-care characteristics and decisions was
      investigated. Mothers' employment plans and child-care decisions were affected by
      their children's special needs (chronic health problems; use of adaptive
      equipment; total risks; diagnosis; and mental, motor, and adaptive functioning).
      Child-care characteristics were related most consistently to the children's
      diagnoses. Infants diagnosed with Down syndrome compared with those whose
      developmental delays were of unknown origin entered child care earlier and were
      more likely to be in centers and to be receiving lower quality care.

PMID- 10207576
TI  - Smoking policies and practices in a state-supported residential system for people
      with mental retardation.
AB  - Smoking policies and smoking practices of residents and employees in a state
      supported residential system were investigated. Smoking policies existed in
      almost every agency, although state- and vendor-operated programs had vastly
      different policies. State-operated programs prohibited employees from smoking in
      residences and restricted residents who smoked to designated areas. One third of
      vendor-operated agencies allowed residents and staff members to smoke in
      designated areas, whereas one quarter stipulated that residences be smoke-free.
      Smoking among employees was higher and among residents lower than in the general
      population. The feasibility of specific approaches to reduce passive smoking and
      attitudes and beliefs about human rights issues related to smoking are presented.

PMID- 10207577
TI  - Mortality of persons with developmental disabilities after transfer into
      community care: a 1996 update.
AB  - More than 2,000 persons with developmental disabilities have recently been
      transferred from California institutions into community care. Using data on 1,878
      clients moved between April 1993 and December 1995, Strauss et al. (1998) found a
      corresponding increase in mortality rates. In the present report we update that
      study by analyzing 1996 data. There were 36 deaths, an 88% increase in risk
      adjusted mortality over that expected in institutions, p < .01. We again found
      that persons transferred later were at higher risk than those moving earlier,
      even after adjustment for differences in risk profiles. In the highest
      functioning group, the community mortality rate was tripled. Death certificate
      information was also analyzed.

PMID- 10207578
TI  - Costs of epilepsy in an intermediate care facility for persons with mental
      retardation.
AB  - Epilepsy is a significant comorbid condition in institutionalized persons with
      developmental disabilities and may contribute significant additional costs. This
      study was conducted to provide an estimate of the costs of epilepsy from the
      institutional perspective. Costs were measured retrospectively for 50 persons
      with epilepsy and 50 persons without epilepsy matched by severity of
      developmental disability. A time and motion study was employed to assign
      opportunity costs to documented nursing and physician activities. Two separate
      methods of attribution were used and incremental costs attributable to epilepsy
      were found to be approximately $825 and $918 per person over a 6-month period.
      The following categories accounted for costs: personnel (47.0%), drug (39.6%),
      hospitalization (9.4%), and laboratories/procedures (4.0%). Results are useful
      for describing the economic burden of epilepsy.

PMID- 10207580
TI  - Review of strategies for treating sleep problems in persons with severe or
      profound mental retardation or multiple handicaps.
AB  - During the last 15 years, researchers have shown that a large percentage of
      persons with severe or profound mental retardation or multiple handicaps have
      serious sleep problems. These problems can cause emotional and physical burdens
      for caretakers, interfere with the persons' daily learning and occupational
      performance, and/or exacerbate deviant behaviors. Several studies have been
      conducted to assess behavioral and pharmacological strategies (e.g., bedtime
      fading and response cost, extinction, chronotherapy, and the use of melatonin)
      for reducing sleep problems. Those studies are reviewed here and the
      effectiveness, suitability, practicality, and acceptability of the strategies are
      discussed. Relevant issues for future research are also examined.

PMID- 10207579
TI  - Refining behavioral phenotypes: personality-motivation in Williams and Prader
      Willi syndromes.
AB  - Despite behavioral differences, individuals with Williams or Prader-Willi
      syndrome share a proneness to certain personality characteristics. We
      hypothesized that there are qualitative differences in these shared personality
      features. Personality-motivation (measured using the Reiss Profiles) was compared
      for equal numbers of age- and gender-matched individuals with Williams or Prader
      Willi syndrome or mental retardation due to nonspecific causes. Each syndrome
      featured aberrant motivational profiles, and similarities were found across
      groups in various domains. Significant differences emerged in the specific
      stimuli that motivated behavior in several Reiss Profile domains. Implications
      are discussed for the "classic" sociable personality in Williams syndrome and for
      compulsivity in Prader-Willi syndrome. Recommendations are made for treatment and
      more refined phenotypic research.

PMID- 10207581
TI  - Patterns of adaptive behavior in very young children with autism.
AB  - The Vineland Adaptive Behavior Scales were used to investigate patterns of
      adaptive behavior in children with autism who were under 36 months of age.
      Subjects were 30 children with autism and 30 children with developmental delay
      matched on CA and MA. Relative to controls, the autistic group demonstrated
      weaker socialization and communication skills and greater discrepancies between
      adaptive behavior and MA. Different patterns of relations between adaptive
      behavior domains and cognitive and language skills were obtained for the two
      groups. Preliminary support for the utility of adaptive behavior profiles in
      identifying subgroups of children with autism is provided. Results are discussed
      in terms of their implications for early diagnosis of autism.

PMID- 10207582
TI  - Distinguishing low levels of social support and social strain: implications for
      dual diagnosis.
AB  - Low social support is known to be a risk factor for mental illness in the general
      population. Social strain, or stressful social interaction, has also been shown
      to correlate highly with psychopathology but has been largely ignored for
      individuals with mental retardation. Results based on staff ratings of 104 adults
      with mental retardation are presented, highlighting the relationship among
      support, social strain, and psychopathology. Data suggest that social strain is
      more strongly associated with psychopathology than are overall low levels of
      social support for individuals with mental retardation.

PMID- 10207583
TI  - A symposium on psychotherapy in the age of managed care.
AB  - This article is based upon a symposium presented at Vanderbilt University Medical
      Center on the Department of Psychiatry's 50th anniversary (September 20, 1997).
      The panel of psychotherapy scholar-clinicians discusses issues including: whether
      or not managed care and psychotherapy are compatible; the relevance of the
      Consumer Reports' psychotherapy study to MCOs' emphasis on brief therapy; how
      MCOs impact upon the therapist-patient relationship; the effects of MCOs on the
      psychotherapist's personal and professional identity; and training
      psychotherapists in the era of managed care. The paper is dedicated to Pietro
      Castelnuovo-Tedesco, M.D., Vanderbilt's Blakemore Professor of Psychiatry, who
      died on January 24, 1998.

PMID- 10207584
TI  - Assessment of suitability for psychotherapy. II. Assessment based on basic
      process goals.
AB  - Part II of this paper presents an outline for the assessment of suitability for
      psychotherapy based on the patient's ability to participate in the basic tasks of
      the therapeutic process and provides a coherent approach to this complex and
      difficult task. Several factors, such as therapeutic interaction and relational
      history, influencing the patient's ability to form a productive working
      relationship can be assessed clinically and are well supported by research.
      Others, such as motivation and supportive life circumstances, although less
      supported by research, still appear to be clinically important. Influences on the
      ability to create a model of the patient's psychopathology, such as
      introspection, circumscribed focus, and some aspects of the model itself, are
      supported by limited research but important for some therapies. There is little
      research on trial interventions, though these remain a crucial assessment
      dimension for short-term therapies, particularly. Countertransference, although
      traditionally not viewed as part of assessment, is actually an important tool
      that has been validated by research.

PMID- 10207585
TI  - Curiosity: reflections on its nature and functions.
AB  - This paper attempts to clarify the nature, function and centrality of curiosity
      in the development of object relations and the consolidation of the self. It
      demonstrates how the primary relationship between the infant and the care-giver
      influences the development of curiosity, the ability to use it productively for
      thinking and for building the internal world. Curiosity, in its schizoparanoid
      forms, is an attempt at freezing states of primary undifferentiatedness. In its
      more mature forms, it serves as an integrative agent and signifies both the
      possibility and the need to know, as well as the boundaries of knowledge. It is
      an essential element in the individual's psychic fabric and counterbalances
      splitting and projective identification. Hence, in analysis, it is vital to be
      constantly attentive to all the diverse expressions of curiosity or, conversely,
      to its absence. In the transference, the analyst, as well as the analytic
      setting, often become the aims of that curiosity and its containers. By allowing
      curiosity and surviving it, curiosity is transformed from an expression of
      destructiveness and disintegrating intrusiveness to a necessary prerequisite for
      psychological growth, self-discovery and creativity. Several vignettes illustrate
      the impact of curiosity during therapy.

PMID- 10207586
TI  - The fate of the unconscious in future psychotherapy.
AB  - It is important in these changing times to reconsider the psychoanalytic
      conception of the unconscious and the phantasmal mental life that occupies it--so
      that we can recalibrate our clinical work with it. It is the foundation of all
      our endeavors. Recent developments in neurobiology, combined with a more
      pragmatic intersubjective approach in psychoanalysis and psychotherapy, have
      marginalized the status of the unconscious in the eyes of many mental health
      professionals. Moreover, considerations of realistic childhood traumata and
      neglect are being more and more counterposed to the traditional concept of the
      infantile neurosis. What is at stake is a dismissal of a concept that is still of
      enormous importance, yet one that has been too little understood. What is
      required is a dual-track conception in which an interplay can be seen to be
      taking place between the unconscious, neurobiology, and trauma in the
      intrasubjective as well as in the intersubjective matrix.

PMID- 10207587
TI  - Applying Fairbairn's object relations theory to the dynamics of the battered
      woman.
AB  - Fairbairn's secular object relations model of the development of the human
      personality emphasizes the power of the environment to form inner ego structures
      and the ensuing tragic results for all human infants who are faced with an
      unnurturing environment. Every act that children take to insure their continuing
      attachment to a frustrating, yet tantalizing object undermines their developing
      ego structure. The consequence of severely compromised ego structures is
      repetition compulsion in adulthood, as illustrated by the battered-woman
      syndrome. Each of the engorged and unrealistic part-ego structures seeks out
      external objects to re-enact the original relationship that created them. The
      consequence of a severely rejecting childhood can be endless abuse or death.

PMID- 10207588
TI  - Impasse or pseudo-impasse in the psychotherapy of an inhibited writer.
AB  - This paper describes the interactions of a patient and her therapist in the
      course of psychoanalytic psychotherapy, during which there occurred two
      significant impasse enactments. At first sight, each resembled a classical
      impasse. On further review of the case, the interactions took on a different
      texture that we have described as a pseudo-impasse in the course of the therapy.
      The enactments took the form of an abrupt cessation of the therapy in which the
      patient terminated and then later returned, thereby giving a more intense rhythm
      to the therapy. The patient, described as a sexually inhibited novelist with
      symptoms of panic and anxiety, said at the outset that she was never able to
      express strong feelings for fear of criticism. Central issues included a number
      of conflicts: the manner of referral in which her friend (who was also a friend
      of the therapist) was instrumental; the grief for her dead mother and her lost
      sister; and overt conflict with her critical father. These conflicts became re
      enacted within the interactions between herself and her therapist. The stages of
      therapy could best be described as at first wishing her therapist to be her "sin
      eater," and, subsequently, her idealized, loving, nonjudgemental parent. We
      understand the pseudo-impasses to represent psychotherapeutically framed
      developmental steps.

PMID- 10207589
TI  - The phenomenology of Erwin Straus and the epistemology of psychoanalysis.
AB  - The contributions of Erwin Straus, a phenomenologist psychiatrist of reknown in
      Europe but little known in the United States are summarized. His emphasis on the
      wholeness of the world as it unfolds in its sensory splendor, as opposed to the
      traditional psychiatric efforts toward the reduction of psychic experience into
      quasi-mathematical and medical categories is explained.

PMID- 10207590
TI  - How did they survive? Mechanisms of defense in Nazi concentration camps. 1948.

PMID- 10207591
TI  - [Pro or con accessory anesthesia breathing systems].

PMID- 10207593
TI  - [Surgery for lung volume reduction].
AB  - OBJECTIVES: To define the place of lung volume reduction surgery (LVRS) for non
      bullous emphysema, to discuss the mechanisms of postoperative functional
      improvement and to suggest guidelines for perioperative medical management. DATA
      SOURCES AND EXTRACTION: The Medline data base was searched for any article
      (original papers, editorials, comments, reviews) published in English, French or
      German, from 1980 to April 1998. The key words were: lung volume reduction
      surgery, emphysema, respiratory failure, anaesthesia, lung transplantation. The
      data have been analysed to explain the physiological mechanisms underlying the
      postoperative improvements and to assess the risk-benefit ratio associated with
      LVRS. Finally, proposals are suggested for selection criteria and perioperative
      medical strategies. DATA SYNTHESIS: Besides pharmacological treatment and lung
      transplantation, LVRS is considered as an alternative treatment for patients with
      end-stage pulmonary emphysema. Perioperative management includes selective lung
      ventilation, continuous peridural analgesia and a general anaesthetic technique
      that can be easily reversed. Care should be taken to detect and rapidly correct
      dynamic hyperinflation, pneumothorax, tube malpositioning and major air leaks. In
      a majority of selected patients (70-80%), resection of 20-30% of lung volume
      produces significant clinical and physiological improvement (dyspnoea, exercise
      capacity, FEV1, VO2max), as well as of the quality of life that has been
      attributed to greater elastic recoil, reduced respiratory workload and better
      diaphragmatic and right ventricular function. The most common complication is
      prolonged air leaks. In-hospital mortality varies widely (0-20%, with a median
      value at 4%), depending in part on the experience of the surgical team and on the
      selection criteria. Several factors may predict an unfavourable outcome: advanced
      age, hypercapnia, diffuse emphysema, predominant airway disease and previous
      thoracic surgery. CONCLUSIONS: According to the favourable preliminary results
      and an acceptable incidence of perioperative complications, LVRS is presently
      considered as a new therapeutic option for some patients with respiratory
      failure. Future clinical studies should be focused on appropriate selection
      criteria, operative techniques and long term outcome data.

PMID- 10207592
TI  - [Phare study. Comparative study of combined cefepime-amikacin versus ceftazidime
      combined with amikacin in the treatment of nosocomial pneumonias in ventilated
      patients. Multicenter group study].
AB  - OBJECTIVE: To compare the associations of cefepime (2 g x 2/day) + amikacin (7.5
      mg.kg-1 x 2/day) (= cefe-ami) and ceftazidime (2 g x 3/day) + amikacin (7.5 mg.kg
      1 x 2/day) (= cefta-ami) in patients under mechanical ventilation suffering from
      a nosocomial pneumonia. STUDY DESIGN: Multi-centre, open, comparative, randomised
      study. PATIENTS: The study included 275 ICU patients enrolled either in the cefe
      ami group (n = 141) or in the cefta-ami group (n = 134). METHODS: All cases were
      reviewed in a blinded fashion by the steering committee. RESULTS: Microbiology
      laboratory tests were positive in 74% of patients of the cefe-ami group and in
      63% of the cefta-ami group respectively; 319 presumed causative strains of
      bacteria were isolated. The mean duration of treatment was 12 days for cefepime,
      11 days for ceftazidime and 8 days for amikacin. In intention to treat, the
      clinical recovery rate was 48.2% in the cefe-ami group and 44.8% in the cefta-ami
      group respectively. In the population with a documented pneumonia, the clinical
      recovery was significantly better in the cefe-ami group (53.3%), than in the
      cefta-ami group (39.3%) (P = 0.05). In per protocol analysis, these rates reached
      67.7% in the cefe-ami group and 68.2% in the cefta-ami group respectively. In the
      bacteriologically documented cases the eradication rates were 86.5% and 89.3%
      respectively. CONCLUSION: The efficacy rates of cefe-ami and cefta-ami
      combinations were similar in ICU patients under mechanical ventilation with a
      nosocomial pneumonia. However the cefe-ami association was significantly more
      efficient in the population with a bacteriologically documented pneumonia.

PMID- 10207594
TI  - [Red cell substitutes: perfluorocarbon emulsions and hemoglobin solutions].
AB  - OBJECTIVE: To review the current data on perfluorocarbon (PFC) emulsions and
      haemoglobin (Hb) solutions. DATA SOURCES: For this paper we analysed the
      literature using Medline search along with major review articles. DATA SELECTION
      AND EXTRACTION: The collected articles were reviewed and selected according to
      their quality and originality. DATA SYNTHESIS: PFCs are synthetic fluorinated
      hydrocarbons capable of dissolving, at increased FIO2, large amounts of oxygen.
      They deliver oxygen at tissular level, and are administered as emulsions
      containing particles of around 0.1 micron, reaching the smallest vessels. They
      are exhaled unchanged by the lungs within 7 days. The first clinically used PFC
      was Fluosol-DA 20%. Currently, Oxyfluor 40% and Oxygent 60% are under evaluation.
      PFCs are not true blood substitutes, but rather a means to support tissue
      oxygenation during extreme haemodilution. Solutions of free Hb do not require
      compatibility testing and are fully saturated with oxygen at ambient FIO2. Hb is
      either human, bovine or recombinant Hb. In order to maintain adequate
      intravascular half-life and affinity for oxygen, the Hb molecules are modified by
      internal cross-linking, polymerisation and encapsulation. After promising results
      using animal models, some of these modified Hb solutions are now undergoing phase
      III clinical trials. Among these, diaspirin cross-linked haemoglobin (DCLHb) has
      been tested in cardiac and orthopaedic surgery, as well as in trauma patients.
      The initial results of these multicentre trials are currently being analysed.

PMID- 10207595
TI  - [Effect of inhaled nitric oxide in a patient with intracranial hypertension].
AB  - Inhaled nitric oxide (NO) may be beneficial in patients with acute respiratory
      distress syndrome (ARDS). The effects of inhaled NO on intracranial pressure have
      not yet been assessed. This case shows the beneficial effects of inhaled NO in a
      patient with ARDS and intracranial hypertension.

PMID- 10207596
TI  - [Interactions between naltrexone, an opioid antagonist, and opioids administered
      during general anesthesia].
AB  - We report a case of a probable interaction between sufentanil and naltrexone, an
      oral long acting opioid antagonist, prescribed for maintenance of abstinence in
      alcoholics and opioid addicts. The interaction resulted in an antagonisation of
      the effects of sufentanil and the necessity to increase the dosage. Anaesthetists
      should be aware of this potential drug interaction.

PMID- 10207597
TI  - [Autologous transfusion and hemoglobin SC disease].
AB  - Three autologous blood units were transfused during elective orthopaedic surgery
      in a patient with undiagnosed haemoglobin SC disease. The packed red blood cells
      had been stored at 4 degrees C on SAG-M under standard conditions for 10 to 31
      days. There was no evidence of adverse clinical reactions during the
      perioperative period. Six months later, a blood unit was collected at the initial
      step of an exchange transfusion in the same patient. Haemolysis was moderate
      after a 12-day-storage period and more significant after 32 days. This
      observation, as some other case reports, suggest that autologous blood
      transfusion may be considered for haemorrhagic surgery in selected patients with
      sickle cell disease.

PMID- 10207598
TI  - [Sufentanil in balanced anesthesia: need to predict concentrations for dose
      optimization].
AB  - During balanced anaesthesia sufentanil may be difficult to use, as the required
      doses change over time depending on the patient and the noxious stimuli. Patient
      adjustment may be improved by using pharmacokinetic simulations that predict the
      concentration achieved in the body. In the first case report, sufentanil was
      given manually as repeated boluses, then by infusion. As haemodynamic status
      remained unstable, a simulation of the sufentanil concentration time course was
      started during the case. It showed that instability had pharmacokinetic
      explanation and allowed to determine the adequate sufentanil concentrations (0.30
      0.40 ng.mL-1 + N2O + isoflurane 0.8-1 vol% for abdominal surgery). However,
      adjusting the doses manually required numerous human actions. In the second case,
      sufentanil was given as a computer-controlled infusion. The adequate
      concentrations were determined (0.15-0.20 ng.mL-1 + N2O + isoflurane 0.4 vol% for
      peripheral surgery in an aged cardiac patient). They were maintained with a
      limited number of human actions and resulted in satisfactory haemodynamic
      stability.

PMID- 10207599
TI  - [Accessory anesthetic breathing systems: verification before use].
AB  - Accessory or ancillary anaesthesia breathing systems can be defined as all those
      connected to the fresh gas outlet of the anaesthetic apparatus and used instead
      of the circle system associated with the ventilator, which is the main circuit.
      They include: the Mapleson systems, the systems with a nonrebreathing valve and
      the disposable systems with a carbon dioxide absorber. They can be a cause of
      major accidents when not checked before and monitored during use. This technical
      note describes techniques of preanaesthetic checking and monitoring during
      anaesthesia.

PMID- 10207600
TI  - [The Medical Device Surveillance Central Commission. Evaluation and
      perspectives].
AB  - In France, a national surveillance commission for medical devices ("Commission de
      Materiovigilance") functions to a) analyse declarations of incidents/accidents
      occurring or liable to occur with medical devices; b) propose preventive
      measures; c) propose surveys or studies concerning the practice of
      materiovigilance. One of the eight sub-commissions is in charge of the problems
      raised by devices used in anaesthesia and intensive therapy. The commission
      considered 406 alarm forms in 1996, 986 in 1997 and 1,200 were expected to arrive
      in 1998. This strong increase is observed because users of medical devices have
      become aware that declaration of incidents/accidents has become compulsory and
      because of the medico-legal risk. With the generalisation of local correspondents
      for materiovigilance and their filtering office, the amount of significant
      declarations reaching the national commission is expected to decrease. Among the
      624 fully processed "alarm forms", at the time of writing this article, 407 (65%)
      were incidents without or only with minor consequences, 206 (33%) were
      significant accidents and 11 (2%) were associated with a lethal outcome. Non
      compliance with the instructions for use and a failure of the device were the
      main causes for incidents/accidents. Major corrective measures were mainly taken
      for misconceptions and quality insurance in production of the devices.

PMID- 10207601
TI  - [Daily medical device surveillance].
AB  - In France the manufacturer, the user of a medical device and all those informed
      of an event or a risk for an event caused by the device and resulting in death or
      the deterioration of the health status of a patient must declare the event
      without delay to the appropriate administrative authority. The witness of the
      event informs either the local correspondent for materiovigilance, when
      available, or the ministry directly. A major objective of the local correspondent
      is to act as a filter and to select among the declarations of events those to be
      transmitted without delay or quarterly to the ministry, and those to be
      registered only locally. Within 48 hours the ministry: a) returns an
      acknowledgement with instructions how to proceed with the involved device; b)
      communicates the declaration to the chairman of the ad hoc subcommission; c)
      informs the manufacturer of the device. The chairman decides on the degree
      severity (major event requiring an immediate investigation, event requiring an
      investigation, event to be entered in a follow-up programme). In the first two
      cases an investigation is undertaken by one or several members of the
      subcommission in co-operation with the manufacturer and the declarant of the
      event. Conservative measures can be undertaken to prevent the re-occurrence of an
      event either with the involved and/or with similar devices and to facilitate the
      investigation.

PMID- 10207602
TI  - [Maintenance and obsolescence of medical devices].
AB  - Maintenance of medical devices is either curative, in case of a failure of the
      device, or preventive. Preventive maintenance (PM) is undertaken either at
      constant time intervals or when a given parameter crosses a specified limit. The
      aim of PM is to amend wear from intensive use as well as from ageing. Normally,
      the modalities of PM are defined by the manufacturer who must anticipate the
      possible deficiencies of the device. Some manufacturers tend to recommend
      exaggerated maintenance procedures. Obsolescence of a medical device is defined
      by one of the following criteria: a) loss of its initial performances; b)
      development of medical techniques requiring a wider spectrum of performances; c)
      presence of new devices with improved securities.

PMID- 10207603
TI  - [Cellular energy metabolism: physiologic and pathologic aspects].
AB  - Cellular homeostasis requires permanent energy production and consumption.
      Adenosine triphosphate (ATP) is the major energy component for the cell. Its
      synthesis occurs mainly in mitochondria where the oxidative phosphorylations
      realise the coupling between oxygen consumption and phosphorylation of adenosine
      diphosphate. The anaerobic production of ATP plays an important role in the
      intermediary metabolism. The enzymatic complexes of the mitochondrial respiratory
      chain are energy transducers acting as proton pumps. In cardiomyocytes, the
      phosphocreatine circuit allows a substrate channelling between mitochondria and
      myofibrils. This metabolic compartmentation explains the difficulties of studying
      energetic metabolism in the beating heart and the lack of correlation between
      cardiac function and the usual energy parameters. Mitochondria are a potential
      site of action of anaesthetic agents. Lipophilic local anaesthetics impair
      cellular energy metabolism and mitochondrial ATP production. Such effects could
      be associated with toxic effects of these molecules. NMR or near-infrared
      spectroscopy are non invasive techniques for monitoring energetic metabolism in
      vivo. Clinical applications are developed for analysing brain, muscle or cardiac
      function in physiological and pathological conditions.

PMID- 10207605
TI  - [Use of locoregional anesthesia in prehospital medicine].

PMID- 10207604
TI  - [Economic impact of the consensus conference guidelines on postoperative
      artificial nutrition in the Rhone-Alps region].
AB  - OBJECTIVES: To assess the economic impact of the French guidelines produced by
      the 1994 consensus conference on postoperative artificial nutrition (AN) in
      elective surgery. STUDY DESIGN: Multicentre before-after study, conducted on a
      cost-containment model from the hospital perspective. PATIENTS AND METHODS: Ten
      hospitals were randomly selected in the Rhone-Alpes area, after a stratification
      of hospital category. Twenty consecutive patients, who underwent upper and lower
      abdominal surgery in each hospital, were included over each study period. Data
      were collected on site by investigators from patients' records before (1994) and
      after (1995) guidelines had been circulated. The calculated costs were direct and
      partial medical and non medical staff costs of a one-day parenteral nutrition.
      They included nutrients, disposable devices, staff time and laboratory tests.
      RESULTS: Between 1994 and 1995, the study showed a 7.4% decrease in the
      postoperative prescription rate of AN, a 4.7% increase in the duration of AN and
      a 3.6% (FF 74.07 constant francs per patient) increase in the total cost of AN in
      surgical patients. Guidelines had mainly a positive impact in patients suffering
      from denutrition, as the duration of postoperative AN increased by 23.7% in this
      group, leading to a 65.1% (FF 175.53) increase in cost in 1995. CONCLUSIONS: The
      cost variable is a valuable indicator of the impact of practice guidelines, as it
      includes the rate and duration of prescriptions. The consensus conference had a
      significant impact in patients suffering from denutrition. Conversely, only minor
      changes in practices concerning patients non suffering from denutrition have been
      observed, leading to a slight cost increase in AN.

PMID- 10207606
TI  - [Cruralgia paresthetica: an unusual presentation of a ruptured abdominal aortic
      aneurysm].

PMID- 10207607
TI  - [Iliofascial block in prehospital care].

PMID- 10207608
TI  - Phospholipase A2 inhibitors p-bromophenacyl bromide and arachidonyl
      trifluoromethyl ketone suppressed interleukin-2 (IL-2) expression in murine
      primary splenocytes.
AB  - Phospholipase A2 (PLA2) has been postulated to play a role in the regulation of
      cytokine expression. Therefore, the objective of the present study was to
      investigate the effects of PLA2 inhibitors p-bromophenacyl bromide (BPB) and
      arachidonyl trifluoromethyl ketone (AACOCF3) on interleukin-2 (IL-2) expression
      in murine primary splenocytes. Pretreatment of the splenocytes with both BPB and
      AACOCF3 suppressed phorbol 12-myristate 13-acetate plus ionomycin-induced IL-2
      secretion in a concentration-dependent manner. Inhibition > 90% of IL-2 secretion
      was observed at 1 microM BPB and 10 microM AACOCF3 compared to the respective
      vehicle control. Likewise, IL-2 steady-state mRNA expression was inhibited by
      both PLA2 inhibitors in a concentration-dependent fashion with > 90% inhibition
      at 1 microM BPB and 20 microM AACOCF3. Taken together, these data demonstrated
      that PLA2 inhibitors BPB and AACOCF3 are robust inhibitors of IL-2 expression at
      both the mRNA and protein levels in murine splenocytes. Moreover, these findings
      suggest that drugs and chemicals which inhibit PLA2 may have marked effects on T
      cell function.

PMID- 10207609
TI  - Dimethylphosphoryl-inhibited human cholinesterases: inhibition, reactivation, and
      aging kinetics.
AB  - Human poisoning by organophosphates bearing two methoxy groups, e.g. by
      malathion, paraoxon-methyl, dimethoate and oxydemeton-methyl, is generally
      considered to be rather resistant to oxime therapy. Since the oxime effectiveness
      is influenced not only by its reactivating potential but also by inhibition,
      aging and spontaneous reactivation kinetics, experiments were performed with
      human acetyl- (AChE) and butyrylcholinesterase (BChE) to determine the respective
      kinetic constants. The efficacy of obidoxime in reactivating dimethylphosphoryl
      AChE was 40, 9 and 3 times higher than of HI 6, pralidoxime and HLo 7,
      respectively. Aging (t1/2 3.7 h) and spontaneous reactivation (t1/2 0.7 h)
      occurred concomitantly, with the portion of the aged enzyme being dependent on
      the presence of excess inhibitor. Calculation of steady-state AChE activity in
      the presence of inhibitor and oxime revealed that obidoxime was superior to
      pralidoxime. In addition, organophosphate concentrations up to 10(-6) M (paraoxon
      methyl) and 10(-4) M (oxydemeton-methyl) could be counteracted at clinically
      relevant oxime concentrations (10 microM). These data indicate that oximes may
      effectively reactivate human dimethylphosphoryl-AChE. Failure of oximes may be
      attributed to megadose intoxications and to prolonged time intervals between
      poison uptake and oxime administration. The potency of the oximes to reactivate
      dimethylphosphoryl-BChE was much lower and the spontaneous reactivation slower
      (t1/2 9 h), while aging proceeded at a comparable rate. Thus, BChE activity
      determination for diagnosis and therapeutic monitoring may give no reliable
      information on AChE status.

PMID- 10207610
TI  - Activity of O6-methylguanine DNA methyltransferase in mononuclear blood cells of
      formaldehyde-exposed medical students.
AB  - A recent study reported that exposure of student embalmers in Cincinnati to high
      concentrations of formaldehyde (2 mg/m3) reduced the activity of the DNA repair
      protein O6-methylguanine DNA methyltransferase (MGMT). Reduction in a DNA repair
      enzyme may strongly increase the cancer risk not only with respect to the repair
      enzyme causing agent but with respect to all carcinogens causing lesions subject
      to repair by the enzyme in question. Thus, we examined whether formaldehyde
      exposure of 57 medical students during their anatomy course at two different
      Universities in Germany influenced MGMT activity in mononuclear blood cells. Mean
      formaldehyde exposure of 41 students was 0.2 +/- 0.05 mg/m3 for 6 h per week.
      MGMT activity was 133.2 +/- 14.9 fmol MGMT/10(6) cells before the beginning of
      the formaldehyde exposure, 131.1 +/- 15.8 fmol MGMT/10(6) cells after 50 days (P
      = 0.56) and 128.2 +/- 19.0 fmol MGMT/10(6) cells after 111 days of exposure (P =
      0.92). Similarly, no significant influence of formaldehyde exposure was observed,
      when smoking habits, alcohol consumption, allergic disease and sex of students
      were considered. In addition no significant difference was obtained in MGMT
      activity between 16 students with mean formaldehyde exposure of 0.8 +/- 0.6 mg/m3
      and students without formaldehyde exposure (n = 51; P = 0.37). In conclusion,
      exposure of the medical students in western Europe to formaldehyde did not
      decrease MGMT activity in mononuclear blood cells.

PMID- 10207611
TI  - Behavioral abnormalities and apoptotic changes in neurons in mice brain following
      a single administration of allylnitrile.
AB  - A single dose of allylnitrile in mice might induce persistent behavioral
      abnormalities, of which the mechanism is not yet known. The present study was
      undertaken to explore the relationship between behavioral abnormalities and
      pathological changes in the brain of mice following exposure to allylnitrile.
      Exposure to allylnitrile (63, 84, and 112 mg/kg, p.o.) resulted in dose-dependent
      changes in behavioral abnormalities, including increased locomotor activity,
      circling, retropulsion, head twitching, and alteration in reflexive behavior,
      which appeared at day 2 postdosing and were persistent throughout the
      experimental period (60 days) at the higher dose levels. Allylnitrile produced
      neuronal retraction including hyperchromasia of the nuclei in the raphe nuclei,
      cerebral cortex, hypothalamus, hippocampal CA1 and dentate gyrus later than 30
      days. No gliosis was observed in these regions. Not all but a significant number
      of neurons in the hippocampal CA1, medial habenula and raphe nuclei were immuno
      reactive to CPP32 (Caspase-3) even at day 2. These neurons were also positive to
      Hoechst 33258 staining, indicating allylnitrile caused apoptotic changes in
      specific neurons when neuronal behaviors became apparent. These apoptotic changes
      were persistent even in the area without neuronal contraction such as medial
      habenula. However, almost all neurons in these areas were also positive to
      terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling
      (TUNEL). It is conceivable that allylnitrile caused apoptotic changes in neurons
      but did not always lead them to cell death immediately. Moreover, even when
      neuronal contraction resulted in retention of behavioral abnormalities, onset of
      these abnormalities seems to be associated with the impairment in the habenulo
      raphe relay due to activation of apoptotic cascade in neurons.

PMID- 10207612
TI  - Metabolism of benzene in human liver microsomes: individual variations in
      relation to CYP2E1 expression.
AB  - In human liver microsomes the oxidations of benzene, chlorzoxazone, aniline,
      dimethylformamide, and 4-nitrophenol were significantly correlated with each
      other and with the level of cytochrome P450 (CYP) 2E1 estimated by
      immunoblotting. Moreover, benzene oxidation to water-soluble metabolites was
      suppressed by 0.1 mM diethyldithiocarbamate, supposedly a specific inhibitor of
      CYP2E1 at this level. None of these metabolic rates correlated with
      immunochemically determined levels of CYP1A2, 2C9, and 3A4 nor oxidation of 7
      ethoxyresorufin, tolbutamide, and nifedipine. Benzene oxidation to water-soluble
      metabolites was characterized by typical Michaelis-Menten kinetics. The different
      benzene K(m) values seen in individual human microsomal samples were not
      correlated with the level or activity of CYP1A2, 2C9, 2E1, and 3A4 but could be
      due to CYP2E1 microheterogeneity. The lowest K(m) for benzene oxidation could be
      related to C/D and/or c1/c2 polymorphism of CYP2E1 gene. Covalent binding of
      benzene reactive metabolites to microsomal proteins was also correlated with the
      CYP2E1 metabolic rates and immunochemical levels. At high concentrations of
      benzene covalent binding was inversely related to benzene concentrations (as well
      as to formation of water-soluble metabolites) in agreement with the view that
      secondary metabolites, mainly benzoquinone, are responsible for the covalent
      binding.

PMID- 10207613
TI  - Mechanism of decrease in levels of hepatic P450 isozymes induced by intracerebral
      endotoxin: independence from sympathetic nervous and adrenocortical systems.
AB  - We previously reported that lipoplysaccharide (LPS) injected
      intracerebroventricularly (i.c.v.) at an ineffective dose (0.1 microgram/rat)
      decreased the drug metabolizing activities and related cytochrome P450 (CYP)
      isozymes in rat liver microsomes when injected intraperitoneally (i.p.). The dose
      study (doses < 0.1 microgram intracerebrally and > 0.1 microgram i.p.), which was
      carried out to examine how much more effective is i.c.v.-LPS than i.p.-LPS,
      showed that the pattern of alteration of expression of CYP isozymes induced by
      i.c.v.-LPS was different from that caused by i.p.-LPS at an effective dose (10
      micrograms/rat). These results indicate that the decrease in hepatic CYP isozymes
      caused by i.c.v.-LPS could not be explained by the LPS leaked from the brain,
      suggesting that the decrease in hepatic CYP isozymes by i.c.v.-LPS may be caused
      by a central action of LPS. In this study, the possible involvement of
      sympathetic nervous and adrenocortical systems in the down-regulation of CYP
      isozymes by i.c.v.-LPS was investigated using surgical or chemical
      sympathetecomized or adrenalectomized rats. The norepinephrine (NE) content in
      the liver in rats with surgical hepatic sympathetectomy was reduced by 88%
      compared with that of sham-operated rats that received i.c.v.-saline and 85%
      compared with that of sham-operated rats that received i.c.v.-LPS, indicating
      that hepatic denervation was successful. The NE content in the liver in rats
      chemically sympathetectomized by two i.p. injections of 6-hydroxydopamine (40
      mg/kg each time) 1 and 2 days before i.c.v. injection was reduced by 82% in
      i.c.v.-saline-treated and by 74% in i.c.v.-LPS-treated groups compared with that
      in rats pretreated with i.p.-saline. These results indicate that sympathetic NE
      terminals were effectively removed. Intracerebroventricular LPS decreased the
      total P450 content and the activities of CYP dependent drug metabolizing enzymes,
      ethoxyresorufin O-deethylase (EROD), pentoxyresorufin O-depentylase (PROD),
      imipramine N-demethylase (IMND) and erythromycin N-demethylase (ERND) after 24 h
      in both sympathetectomized rats and non-denervated rats. Adrenalectomy (ADX)
      reduced the level of corticosterone in serum by 81% compared to sham-operated
      rats, indicating that adrenalectomy was successful. ADX did not inhibit the
      decrease in the total P450 content and the metabolism of drugs induced by i.c.v.
      LPS, but more profoundly emphasized the inhibitory effect of i.c.v.-LPS than the
      sham-operation. These results suggest that the sympathetic nervous systems both
      directly and indirectly innervating the liver do not participate in the primary
      mechanism of the decrease in the activities of CYP isozymes in rat liver
      microsomes induced by i.c.v.-LPS. Also, the adrenal glands, especially the
      adrenocortical system, play a suppressive role in the decrease in CYP isozymes
      caused by i.c.v.-LPS.

PMID- 10207614
TI  - The phytoestrogens coumoestrol and genistein induce structural chromosomal
      aberrations in cultured human peripheral blood lymphocytes.
AB  - The clastogenic potential of the phytoestrogens coumoestrol (COUM), genistein
      (GEN) and daidzein (DAI) has been studied in human peripheral blood lymphocytes
      in vitro. After exposure of the cultured lymphocytes to 50 to 75 microM COUM or
      25 microM GEN for 6 h, a clear induction of structural chromosomal aberrations
      was observed by cytogenetic analysis. The major alterations were chromatid
      breaks, gaps and interchanges. In contrast, DAI did not induce chromosome
      aberrations even at 100 microM. These results, together with previously published
      reports on the induction of micronuclei and DNA strand breaks in cultured Chinese
      hamster V79 cells by COUM and GEN, but not DAI, suggest that some but not all
      phytoestrogens have the potential for genetic toxicity.

PMID- 10207615
TI  - Effects of 2-phenoxyethanol on N-methyl-D-aspartate (NMDA) receptor-mediated ion
      currents.
AB  - The actions were examined of 17 frequently used glycol ether compounds on the
      glutamate receptor-mediated ion currents. The receptors were expressed in Xenopus
      oocytes by injection of rat brain mRNA. Most of the 17 glycol ethers exerted no
      effects on the glutamate subreceptors activated by kainate and N-methyl-D
      aspartate (NMDA), whereas 2-phenoxyethanol (ethylene glycol monophenyl ether)
      caused a considerable reduction of NMDA-induced membrane currents in a reversible
      and concentration-dependent manner. The threshold concentration of the ethylene
      glycol monophenyl ether effect was < 10 mumol/l. The concentration for a 50%
      inhibition (IC50) was approximately 360 mumol/l. The results indicate a
      neurotoxic potential for 2-phenoxyethanol.

PMID- 10207616
TI  - Pubertal dependent effects of cadmium on episodic prolactin secretion in male
      rats.
AB  - This work was undertaken to assess if exposure to cadmium related to puberty may
      affect the episodic pattern of prolactin. Male rats were submitted to cadmium
      exposure, from day 30 to 60 or from day 60 to 90 of life respectively, at a dose
      of 50 ppm in the drinking water. Control age-matched rats received cadmium-free
      water. Prepubertal cadmium administration decreased mean serum prolactin levels
      and the absolute amplitude of the prolactin pulses. Subchronic exposure to
      cadmium of adult rats decreased mean serum prolactin levels, the absolute
      amplitude of the prolactin pulses and their duration, and the mean half-life of
      the hormone. These results suggest that subchronic cadmium exposure changes the
      secretory pattern of prolactin in adult male rats in a puberty-dependent way.

PMID- 10207617
TI  - Signal transduction by the c-Jun N-terminal kinase.
AB  - The c-Jun N-terminal kinase (JNK) group of mitogen-activated protein kinases (MAP
      kinases) is activated by exposure of cells to environmental stress and by the
      treatment of cells with cytokines. The mechanism of activation of JNK is mediated
      by dual phosphorylation within kinase subdomain VIII on the motif Thr-Pro-Tyr.
      This phosphorylation is mediated by the MAP kinase kinases MKK4 and MKK7. These
      MAP kinase kinases serve as signalling molecules that integrate a wide array of
      stimuli into the activation of the JNK signalling pathway. Studies of the
      physiological function of JNK have been facilitated by the molecular genetic
      analysis of JNK signalling in Drosophila and by the creation of mice with
      targeted disruption of components of the JNK pathway. These studies demonstrate
      that the JNK pathway regulates AP-1 (activator protein-1) transcriptional
      activity in vivo and indicate that JNK is required for embryonic morphogenesis,
      the regulation of cellular proliferation and apoptosis, and the response of cells
      to immunological stimuli.

PMID- 10207618
TI  - Roles of the AMP-activated/SNF1 protein kinase family in the response to cellular
      stress.
AB  - The AMP-activated protein kinase (AMPK) in mammals, and its homologue in
      Saccharomyces cerevisiae, are activated by cellular stresses associated with ATP
      depletion. AMPK is a heterotrimer comprising a catalytic alpha subunit with
      associated beta and gamma subunits, these being homologous with the products of
      the SNF1, SIP1/SIP2/GAL83 and SNF4 genes in S. cerevisiae. The alpha subunit has
      at least two isoforms (alpha 1 and alpha 2), which differ in their AMP-dependence
      and subcellular localization, with alpha 2 complexes being partly nuclear. AMPK
      is activated allosterically by 5'-AMP, which also promotes phosphorylation and
      activation by an upstream kinase, and inhibits dephosphorylation and
      inactivation. Elevation of AMP always accompanies depletion of ATP due to the
      action of adenylate kinase. Since high ATP antagonizes the activating effects of
      AMP, the system behaves like a cellular 'fuel gauge'. It is activated by various
      types of stress associated with ATP depletion, such as hypoxia, heat shock,
      metabolic poisoning and, in muscle, exercise. AMPK phosphorylates multiple
      targets which switch off anabolic pathways and switch on alternative catabolic
      pathways. The yeast SNF1 complex is switched on by glucose starvation, and its
      targets include transcription factors that repress transcription of genes
      required for catabolism of alternative carbon sources.

PMID- 10207619
TI  - Making the connection: coupling of stress-activated ERK/MAPK (extracellular
      signal-regulated kinase/mitogen-activated protein kinase) core signalling modules
      to extracellular stimuli and biological responses.
AB  - Signal-transduction pathways that employ members of the extracellular signal
      regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) family of protein
      Ser/Thr kinases are widely conserved among eukaryotes. The multiplicity of these
      pathways allows the cell to respond to divergent extracellular stimuli by
      initiating a broad array of responses ranging from cell growth to apoptosis.
      ERK/MAPK pathways are comprised of a three-tiered core-signalling module wherein
      ERK/MAPKs are regulated by MAPK/ERK kinases (MEKs) and MEKs, in turn, are
      regulated by MAPK kinase kinases (MAPKKKs). The regulation of MAPKKK-->MEK-
      >ERK/MAPK core-signalling modules by upstream components is poorly understood.
      Mammalian stress-activated ERK/MAPK pathways have been implicated in numerous
      important physiological functions, including inflammatory responses and
      apoptosis. In this review, I will discuss how mammalian stress-regulated ERK/MAPK
      core-signalling modules couple with members of the SPS1 family of protein kinases
      and to other upstream elements, and how these stress-regulated pathways influence
      cell function.

PMID- 10207620
TI  - Stress-activated MAP kinase (mitogen-activated protein kinase) pathways of
      budding and fission yeasts.
AB  - All eukaryotic cells share the ability to sense and rapidly respond to
      environmental stress by initiating cyto-protective programmes of gene expression,
      protein translation and protein degradation. The molecular basis underlying these
      processes is, however, not well understood. Recently, attention has become
      focused on an evolutionarily conserved family of protein kinases called the
      stress-activated mitogen-activated protein kinases (SAPKs) that are activated
      when cells are challenged with a variety of environmental stresses or cytotoxic
      agents. Two members of the SAPK family, HOG1 and Sty1/Spc1, have been identified
      in the distantly related budding and fission yeasts, respectively. This has
      allowed researchers to genetically and biochemically dissect the structure of
      these pathways to begin to understand how they are activated and the role of the
      SAPKs in the cyto-protective response. In this chapter, I compare the structure
      of the SAPK pathways in the two yeasts and illustrate how this knowledge may
      benefit our understanding of stress sensing in mammalian cells.

PMID- 10207621
TI  - Protein kinase cascades in intracellular signalling by interleukin-I and tumour
      necrosis factor.
AB  - Interleukin 1 (IL-1) and tumour necrosis factor (TNF) are major mediators of
      inflammation, with similar actions. Their receptor mechanisms and downstream
      pathways are reviewed. They activate several protein kinases in fibroblasts,
      including the three types of mitogen-activated protein kinase (MAPK), the kinase
      of the inhibitor of nuclear factor-kappa B (I kappa BK), and the TNF-/IL-1
      activated beta-casein kinase. Cultured cells show a broader spectrum of kinase
      activation by IL-1 than tissues in vivo, suggesting that the receptors connect to
      more pathways in proliferating cells than in resting differentiated cells. The c
      Jun N-terminal kinase (JNK) is strongly activated by IL-1 in tissues. In rabbit
      liver this is mediated by MAPK kinase 7; the upstream kinase is unidentified.
      Little is known of downstream MAPK targets in inflammation. Inhibitor experiments
      suggest that p38MAPK mediates induction of cyclo-oxygenase-2 and
      metalloproteinases by IL-1, and of TNF, IL-1 and cyclo-oxygenase-2 by endotoxin
      (in monocytes). p38MAPK is needed for induction of the mRNAs (except IL-1 mRNA).

PMID- 10207622
TI  - Regulation of actin dynamics by stress-activated protein kinase 2 (SAPK2)
      dependent phosphorylation of heat-shock protein of 27 kDa (Hsp27).
AB  - Activation of the mitogen-activated protein kinase (MAP kinase) SAPK2 (stress
      activated protein kinase 2) leads to the phosphorylation of several transcription
      factors and cytoplasmic proteins, and thereby presumably orchestrates important
      specific cellular responses to numerous cytokines, stressing agents and agonists
      of tyrosine kinase or serpentine receptors. The heat-shock protein of 27 kDa
      (Hsp27), a downstream target of the SAPK2-activated MAP-kinase-activated protein
      kinase-2/3, has a documented function as an actin polymerization modulator.
      Accordingly, recent evidence implicates the SAPK2 pathway in the modulation of
      microfilament dynamics in response to stress and agonist stimulation. In vascular
      endothelial cells, where the basal level of expression of Hsp27 is high, SAPK2
      mediates oxidative stress- and vascular endothelial growth factor (VEGF)-induced
      actin reorganization and VEGF-induced cell migration, suggesting a key role for
      this MAP kinase pathway in inflammation and angiogenic processes.

PMID- 10207623
TI  - DNA-dependent protein kinase and related proteins.
AB  - The DNA-dependent protein kinase (DNA-PK) is a nuclear protein serine/threonine
      kinase that must bind to DNA double-strand breaks to be active. We and others
      have shown that it is a multiprotein complex comprising an approx. 465 kDa
      catalytic subunit (DNA-PKcs) and a DNA-binding component, Ku. Notably, cells
      defective in DNA-PK are hypersensitive to ionizing radiation. Thus X-ray
      sensitive hamster xrs-6 cells are mutated in Ku, and rodent V3 cells and cells of
      the severe combined immune-deficient (Scid) mouse lack a functional DNA-PKcs.
      Cloning of the DNA-PKcs cDNA revealed that it falls into the phosphatidylinositol
      (PI) 3-kinase family of proteins. However, biochemical assays indicate that DNA
      PK contains no intrinsic lipid kinase activity, but is instead a serine/threonine
      kinase. We have also found that DNA-PK activity can be inhibited by the PI 3
      kinase inhibitors wortmannin and LY294002. Consistent with its proposed role in
      genome surveillance and the detection of DNA damage, DNA-PKcs is most similar to
      a subset of proteins involved in cell-cycle checkpoint control and signalling of
      DNA damage. Furthermore, the recent cloning of the gene mutated in ataxia
      telangiectasia (A-T) patients, named ATM (A-T mutated), has revealed that the
      product of this gene is also a PI 3-kinase family member and is related to DNA
      PKcs. Although much is known about the clinical symptoms and cellular phenotypes
      that arise from disruption of the A-T gene, little is known about the biochemical
      action of ATM in response to DNA damage. Given its sequence similarity with DNA
      PKcs, we speculate that ATM may function in a manner similar to DNA-PK.

PMID- 10207624
TI  - Stress-induced activation of the heat-shock response: cell and molecular biology
      of heat-shock factors.
AB  - Exposure of cells to environmental and physiological stress leads to an imbalance
      in protein metabolism, which challenges the cell to respond rapidly and precisely
      to the deleterious effects of stress on protein homoeostasis. The heat-shock
      response, through activation of heat-shock transcription factors (HSFs) and the
      elevated expression of heat-shock proteins and molecular chaperones, protects the
      cell against the accumulation of non-native proteins. Activation of HSF1 involves
      a complex multi-step pathway in which the inert monomer oligomerizes to a DNA
      binding, transcriptionally active, trimer which relocalizes within the the
      nucleus to form stress-induced HSF1 granules. Attenuation of the heat-shock
      response involves molecular chaperones which repress the HSF1 transactivation
      domain and HSF-binding protein 1 (HSBP1), which interacts with the HSF1
      oligomerization domain of HSF1 to negatively regulate its activity, thus insuring
      that the expression of chaperones is precisely determined.

PMID- 10207625
TI  - Transcriptional regulation via redox-sensitive iron-sulphur centres in an
      oxidative stress response.
AB  - Genetic responses to oxidative stress are triggered by excessive levels of agents
      such as superoxide. The soxRS regulon of Escherichia coli includes at least a
      dozen oxidative-stress and antibiotic-resistance genes that are activated by the
      SoxS protein, the synthesis of which is controlled by the redox-sensing SoxR
      protein. SoxR is a homodimer of 17 kDa subunits, each of which contains a [2Fe
      2S] cluster. Transcriptional activation by SoxR is controlled by the oxidation
      state of these metal centres. In the absence of oxidative stress, the [2Fe-2S]
      centres are in the reduced form and the protein is inactive, although it still
      binds the soxS promoter. Agents that generate superoxide in the cell (e.g.
      paraquat) cause rapid oxidation of the metal centres, which triggers the
      transcriptional activity of SoxR; removal of the oxidative stress is followed by
      rapid re-reduction of the [2Fe-2S] centres. This facile mechanism links oxidation
      state to control of protein activity and may be used widely to allow cells to
      respond to oxidative stress.

PMID- 10207626
TI  - Adaptive responses to environmental chemicals.
AB  - Adaption to chemical agents in the environment is a fundamental part of the
      evolutionary process and a large number of genes have evolved to specifically
      detoxify potentially harmful chemical agents. These genes can act at various
      levels within cells and determine circulating chemical or toxin concentrations,
      and uptake and efflux rates as well as intracellular detoxification enzymes, such
      as the cytochrome P-450-dependent mono-oxygenases and glutathione S-transferases.
      These multigene families of proteins play a central role in chemical and drug
      detoxification and their polymorphic expression may well be a factor in disease
      susceptibility.

PMID- 10207627
TI  - Cellular response to cancer chemopreventive agents: contribution of the
      antioxidant responsive element to the adaptive response to oxidative and chemical
      stress.
AB  - Cancer chemopreventive agents can act by inhibiting either the acquisition of
      mutations or the neoplastic processes that occur subsequent to mutagenesis.
      Compounds that reduce the rate at which mutations arise, referred to as blocking
      agents, exert their effects largely through their ability to induce the
      expression of antioxidant and detoxification proteins. This is achieved by the
      transcriptional activation of a small number of genes that are co-regulated
      through the presence of an antioxidant responsive element (ARE) in their
      promoters. Blocking agents can cause gene induction by producing oxidative and/or
      chemical stress within the cell and, as the inducible proteins act to ameliorate
      the metabolic insult, the process represents a form of adaptive response. The
      transcription factors which mediate this response through the ARE are members of
      the basic leucine zipper superfamily. The mechanism whereby cells sense and
      respond to the chemical signal(s) generated by chemopreventive blocking agents is
      discussed.

PMID- 10207628
TI  - Smoking and risk of total and fatal prostate cancer in United States health
      professionals.
AB  - Studies that have examined the relationship between cigarette use and prostate
      cancer incidence have yielded inconsistent results, although most studies have
      suggested that smoking is related to the occurrence of fatal prostate cancer. We
      evaluated prospectively the relationship between cigarette smoking and total,
      distant metastatic, and fatal prostate cancer in 47,781 male health professionals
      throughout the United States followed with questionnaires. From 1986 to 1994, we
      documented 1369 men with prostate cancer (excluding stage A1). One hundred fifty
      two of the men had distant metastatic disease at diagnosis, and 103 fatal cases
      occurred from 1986 to 1994. Early (before age 30), late (within recent 10 years),
      and lifetime cumulative smoking history were unrelated to risk of total prostate
      cancer. However, men who had smoked 15 or more pack-years of cigarettes within
      the preceding 10 years were at higher risk of distant metastatic prostate cancer
      [multivariate relative risk (RR), 1.81; 95% confidence interval (CI), 1.05-3.11;
      P (trend), 0.03] and fatal prostate cancer [RR, 2.06; CI, 1.08-3.90; P (trend),
      0.02] relative to nonsmokers. Within 10 years after quitting, the excess risk
      among smokers is eliminated. The higher rate of fatal prostate cancer among
      smokers did not appear to result from confounding by diet or other lifestyle
      factors, different screening behavior between smokers and nonsmokers, or from
      other smoking-related comorbidities. Our results indicate that although smoking
      was unrelated to prostate cancer incidence, recent tobacco use had a substantial
      impact on the occurrence of fatal prostate cancer.

PMID- 10207629
TI  - Glutathione S-transferase-mu (GSTM1) and -theta (GSTT1) genotypes in the etiology
      of prostate cancer.
AB  - The glutathione S-transferases (GSTs) are involved in the metabolism of numerous
      potential prostate carcinogens. Common homozygous germ-line deletions exist in
      the genes that encode GST-mu (GSTM1) and GST-theta (GSTT1) and preclude enzyme
      expression. To evaluate whether GSTM1 and/or GSTT1 contribute to prostate cancer
      (CaP) etiology, we studied 237 incident CaP cases and 239 age- and race-matched
      controls. The probability of having CaP was increased in men who had nondeleted
      (functional) genotypes at GSTT1 (odds ratio, 1.83; 95% confidence interval, 1.19
      2.80) but not GSTM1 (odds ratio, 1.07; 95% confidence interval, 0.74-1.55). No
      interaction of these genes in CaP etiology was observed. GST-theta is highly
      expressed in the prostate and can produce genotoxic effects upon exposure to
      specific carcinogens. These results suggest that GSTT1 is associated with CaP
      risk.

PMID- 10207630
TI  - Polymorphisms in GSTP1, GSTM1, and GSTT1 and susceptibility to colorectal cancer.
AB  - Polymorphisms in glutathione S-transferase (GSTs) may predispose to colorectal
      cancer through deficient detoxification of environmental carcinogens, although
      previous results are conflicting. A study with 178 matched case-control pairs was
      conducted to determine the effect of the GSTT1 and GSTM1 null genotypes and
      polymorphisms in GSTP1 on colorectal cancer susceptibility. In a secondary
      analysis, we examined interactions between genotypes and with the N
      acetyltransferase 2 (NAT2) genotype. Heterogeneity by age, sex, site, and stage
      of cancer was also examined. No effect of any genotype for GSTM1, GSTT1, or GSTP1
      on colorectal cancer susceptibility was detected. Secondary end points showed
      that individuals with both the GSTT1 null and NAT2 slow genotypes combined
      appeared to be at increased risk of colorectal cancer (odds ratio = 2.33; 95%
      confidence interval, 1.1-5.0). We conclude that GST polymorphisms alone do not
      predispose to colorectal cancer in northeast England. We also observed possible
      effects of the GSTT1 null genotype on the age and stage at presentation, and
      these, together with the findings of an apparent interaction with NAT2 genotypes,
      need to be confirmed in further studies.

PMID- 10207631
TI  - High prevalence of antibodies against HERV-K10 in patients with testicular cancer
      but not with AIDS.
AB  - Human endogenous retrovirus K10 (HERV-K10) env and gag expression has been
      detected in placenta, embryonic tissue, and cell lines. By transfection, these
      sequences have been expressed in insect cells and developed into serological
      assays, revealing HERV-K10 antibodies in patients with testicular cancer.
      Patients with AIDS are at an increased risk for testicular cancer and frequently
      reactivate latent infections. We postulated that HERV-K10 seroprevalence might be
      increased with HIV infection or AIDS. Stored, frozen serum samples from 52
      patients with testicular cancer (8 patients with HIV and 30 patients with samples
      near the time of diagnosis) and 84 controls (40 patients with HIV) were diluted
      1:40 and tested by immunofluorescence against SF158 cells transfected with HERV
      K10 env [ENV1.9(+)] or gag (pACGAG). Seroprevalence rates were compared cross
      sectionally in cases and controls, excluding those with indeterminate results (3
      of 30 cases and 7 of 84 controls), and also were examined longitudinally in the
      cases before or after diagnosis of testicular cancer. Seroprevalence to HERV-K10
      Env or Gag was 17 of 27 testicular cancer patients (63%) around the time of
      diagnosis, compared to 4 of 77 controls (5%; P < 0.0001). Seroprevalence was
      similar (50% to 60%) with seminoma, teratocarcinoma, or embryonal carcinoma, and
      it was not increased with HIV infection in either cases (33%) or controls (3%).
      HERV-K10 antibodies were detected in 12 of 19 cases (63%) more than 6 months
      before seminoma diagnosis, as well as in four cases with residual or recurrent
      malignancy more than 1 month after initial diagnosis. Thus, HERV-K10 antibodies
      are detected frequently with testicular cancer and seem to resolve rapidly with
      effective therapy of the malignancy. Antibody reactivity also occurs in
      approximately 5% of controls, perhaps because of nonspecific or cross-reactive
      epitopes. HIV and AIDS were not associated with HERV-K10 antibodies, thus,
      leaving their higher risk of testicular cancer unexplained.

PMID- 10207632
TI  - Comparison of mutations in the p53 and K-ras genes in lung carcinomas from
      smoking and nonsmoking women.
AB  - Lung cancer incidence is increasing in women with little or no tobacco exposure,
      and the cause of this trend is not known. One possibility is increased
      sensitivity to environmental tobacco smoke in women nonsmokers diagnosed with
      lung cancer. To determine whether mutations associated with tobacco exposure are
      found in the lung tumors of women who are lifetime nonsmokers or occasional
      smokers, we compared the p53 and K-ras mutational spectra in lung carcinomas from
      23 female nonsmokers, 2 female occasional smokers (< 10 pack-years), and 30
      female long-term smokers (20-100 pack-years). We also looked for p53 and K-ras
      mutations in three carcinoid lung tumors, two from female nonsmokers and one from
      a female occasional smoker. For the p53 gene, exons 4-8 were examined for
      mutations; for the K-ras gene, exon 1 was examined. No mutations were found in
      the carcinoid tumors. In lung carcinomas, p53 mutations were identified in six
      (26.1%) of the cases from lifetime nonsmokers and consisted of five transitions
      (including three C to T, one G to A, and one T to C) and one T to A transversion.
      In comparison, p53 mutations were identified in 10 (31.3%) of the 32 lung
      carcinomas from short-term and long-term smokers and consisted of six
      transversions (four G to T, one A to T, and one G to C), one A to G transition,
      one C to T transition, and two deletions of one to four bp. Mutations in the p53
      gene found in nonsmokers also occurred in either different codons or different
      positions within a codon compared with those seen in long-term smokers. K-ras
      mutations in codon 12 were identified in two lung carcinomas (8.7%) from lifetime
      nonsmokers. The K-ras mutations found were a G to T transversion and a G to A
      transition. Eight (25%) of the 32 lung carcinomas from smokers contained K-ras
      mutations in codons 12 and 13 (four G to T transversions and four G to A
      transitions). In addition, six silent mutations that are most likely
      polymorphisms were found in both smokers and nonsmokers. These results confirm
      that K-ras mutations are more frequent in smokers than in nonsmokers, but that
      the same type of mutation in the K-ras gene is found in both groups. In contrast,
      although the frequency of mutation in the p53 gene was similar in lifetime
      nonsmokers compared with long-term smokers, the types and spectra of mutation are
      significantly different. Two of the C to T transitions found in nonsmokers, but
      none of those found in smokers, occur at the C of a CpG site. These results
      suggest the mutagen(s) and/or mechanisms of p53 mutations in women nonsmokers are
      different from those responsible for p53 mutations in women smokers, which are
      probably largely induced by tobacco mutagens.

PMID- 10207633
TI  - Chromosomal aberrations in humans induced by urban air pollution: influence of
      DNA repair and polymorphisms of glutathione S-transferase M1 and N
      acetyltransferase 2.
AB  - We have studied the influence of individual susceptibility factors on the
      genotoxic effects of urban air pollution in 106 nonsmoking bus drivers and 101
      postal workers in the Copenhagen metropolitan area. We used the frequency of
      chromosomal aberrations in peripheral blood lymphocytes as a biomarker of
      genotoxic damage and dimethylsulfate-induced unscheduled DNA synthesis in
      mononuclear WBCs, the glutathione S-transferase M1 (GSTM1) genotype, and the N
      acetyltransferase 2 (NAT2) genotype as biomarkers of susceptibility. The bus
      drivers, who had previously been observed to have elevated levels of aromatic DNA
      adducts in their peripheral mononuclear cells, showed a significantly higher
      frequency of cells with chromosomal aberrations as compared with the postal
      workers. In the bus drivers, unscheduled DNA synthesis correlated negatively with
      the number of cells with gaps, indicating a protective effect of DNA repair
      toward chromosome damage. Bus drivers with the GSTM1 null and slow acetylator
      NAT2 genotype had an increased frequency of cells with chromosomal aberrations.
      NAT2 slow acetylators also showed elevated chromosomal aberration counts among
      the postal workers. Our results suggest that long-term exposure to urban air
      pollution (with traffic as the main contributor) induces chromosome damage in
      human somatic cells. Low DNA repair capacity and GSTM1 and NAT2 variants
      associated with reduced detoxification ability increase susceptibility to such
      damage. The effect of the GSTM1 genotype, which was observed only in the bus
      drivers, appears to be associated with air pollution, whereas the NAT2 genotype
      effect, which affected all subjects, may influence the individual response to
      some other common exposure or the baseline level of chromosomal aberrations.

PMID- 10207634
TI  - Effect of aspirin on prostaglandin E2 formation and transforming growth factor
      alpha expression in human rectal mucosa from individuals with a history of
      adenomatous polyps of the colon.
AB  - Colorectal cancer is the second-most frequent cause of cancer mortality in the
      United States. Human epidemiology and laboratory studies indicate that aspirin
      may be an effective colorectal cancer chemopreventive agent. This study was
      designed to determine whether treatment with 81 mg of aspirin per day for 3
      months would alter two putative surrogate end point biomarkers of chemoprevention
      of colorectal cancer [i.e., mucosal prostaglandin E2 (PGE2) formation and
      transforming growth factor alpha (TGF-alpha) expression] in normal-appearing
      rectal mucosa from individuals with a history of adenomatous polyps. Rectal
      biopsies were obtained by flexible sigmoidoscopy at three sequential time points:
      (a) after a 1-month placebo run-in period (baseline), (b) after 3 months of
      ingesting 81 mg of aspirin (as a single tablet) once per day, and (c) after 3
      months of ingesting a placebo tablet once per day (washout period). Daily aspirin
      significantly suppressed PGE2 formation, but this significant suppression was
      completely reversed when aspirin was withdrawn. The extent of TGF-alpha staining
      in rectal crypts was also reduced significantly (P = 0.039) by daily aspirin.
      After a 3-month placebo-washout period, however, the mean extent of TGF-alpha
      staining was not significantly different from either baseline or the aspirin time
      point. Thus, 81 mg of aspirin daily significantly reduced rectal mucosal PGE2
      formation and TGF-alpha expression in patients with a history of adenomatous
      polyps. These putative surrogate end point biomarkers may be useful intermediate
      end points in future colorectal cancer chemoprevention trials.

PMID- 10207635
TI  - CYP2D6 genotype and the incidence of anal and vulvar cancer.
AB  - The risks of anal and vulvar cancer are strongly related to cigarette smoking.
      Smokers are exposed to a substantial quantity of tobacco-specific nitrosamines,
      including 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). NNK is present in
      the mucus of the female genital tract. The enzyme debrisoquine 4-hydroxylase
      (CYP2D6) activates NNK and is present in foreskin kerotinocytes and cervical
      epithelial cells. A polymorphism for the gene CYP2D6 exists, and persons who
      possess alleles that are associated with reduced levels of CYP2D6 activity might
      be expected to be at a relatively lower risk of cancers arising from NNK
      exposure. To test this hypothesis, we conducted a case-control study to examine
      the association of CYP2D6 genotype and the incidence of anal and vulvar cancer
      among cigarette smokers in western Washington State. We tested for 14 alleles (*1
      *12, *14, and *17) among cases (25 men and 43 women with anal cancer, 64 women
      with vulvar cancer) and controls (30 men and 110 women). Contrary to the
      hypothesis, cases were not less likely than controls to have one (43.9 versus
      40.7%) or two (6.8 versus 4.3%) inactivating alleles (*3, *4, *5, *6, *7, *8,
      *11, or *12). There was a suggestion that, if anything, the combined anal and
      vulvar cancer risk increased (rather than decreased) with an increasing number of
      CYP2D6 inactivation alleles: odds ratio = 1.2, 95% confidence interval = 0.7-2.0
      with one inactivating allele; odds ratio = 1.8, 95% confidence interval = 0.6-5.4
      with two inactivating alleles. These results provide no support for the
      hypothesis that cigarette smokers who carry the CYP2D6 alleles that result in a
      low activity phenotype have a decreased risk of anogenital cancer.

PMID- 10207636
TI  - Psychosocial issues in cancer genetics: from the laboratory to the public.

PMID- 10207637
TI  - Correlates of intentions to obtain genetic counseling and colorectal cancer gene
      testing among at-risk relatives from three ethnic groups.
AB  - OBJECTIVES: An understanding of factors associated with interest in genetic
      counseling and intentions to obtain colorectal cancer susceptibility testing is
      an important foundation for developing education, counseling, and genetic
      services and policies. MATERIALS AND METHODS: A survey was mailed to first-degree
      relatives of patients diagnosed with colorectal cancer. The respondents (n = 426,
      77% response rate) are siblings and adult children of Caucasian, Japanese, and
      Hawaiian ethnicity. Data collection was guided by a conceptual framework and
      included questions on demographics, family cancer history, predisposing factors
      (cancer worry, perceived risk, well-being), and enabling factors (decision
      preferences, social support, and health care factors). Logistic regression
      analysis on two binary dependent variables (interest in counseling and intentions
      to get genetic testing) was performed using Generalized Estimating Equations to
      account for family clusters. RESULTS: Forty-five % of respondents were interested
      in genetic counseling, and 26% "definitely" intended to get genetic testing for
      colon cancer when available. For counseling interest, the most important
      predictors were education, Hawaiian ethnicity, cancer worry, and family support.
      Cancer worry, perceived risk, and age (older) were directly, and Japanese
      ethnicity was inversely, associated with testing intentions. CONCLUSIONS: High
      rates of interest in cancer genetic testing are similar to those found in other
      studies. Ethnic differences reveal a paradox between objective population risk
      (higher for Japanese) and greater concerns (among Hawaiians). The substantial
      lack of awareness of family history warrants further research. Culturally
      sensitive education and counseling are needed for managing the likely high demand
      for personalized information about hereditary cancer risk.

PMID- 10207638
TI  - Attitudes toward colon cancer gene testing: survey of relatives of colon cancer
      patients.
AB  - OBJECTIVES: Various studies have identified psychosocial factors that may
      influence attitudes toward colon cancer gene testing. Whereas family history of
      colon cancer has been associated with interest in gene testing, this has not been
      examined extensively. We hypothesized that the strength of family history of
      colon cancer is associated with risk perception and willingness to undergo gene
      testing. MATERIALS AND METHODS: We evaluated attitudes toward colon cancer gene
      testing among persons who had at least one first-degree relative with colon
      cancer. A total of 2680 at-risk relatives in 863 kindreds were identified and
      mailed an extensive survey regarding sociodemographic variables, family history,
      health behaviors and knowledge, and willingness to take a colon cancer gene test.
      A total of 56.6% of persons completed and returned surveys. We conducted a brief
      telephone survey of a random sample of 200 persons who did not respond to the
      mail survey. RESULTS: The combined study sample of 1373 people was 42% male, had
      a mean age of 55 +/- 15 years, was 96% white, and had moderate-to-high SES. A
      total of 77.4% were very likely to take the gene test, and 92.4% were somewhat or
      very likely to take the gene test. A total of 78% of the sample perceived a
      higher colon cancer risk, although patterns of risk perception and worry differed
      significantly between mail survey and telephone survey respondents. More of the
      telephone survey respondents were also somewhat unlikely or very unlikely to take
      the gene test compared to the mail survey respondents (13.7% versus 6.9%). In the
      combined sample, concern about developing colon cancer and risk perception
      increased with number of relatives with colon cancer (P < 0.0001). Eight percent
      expressed no concern about developing colon cancer; 4.8% felt their chance of
      developing colon cancer was lower than others of the same age, sex, and race; and
      3.3% felt that they were very unlikely to develop colon cancer in their lifetime.
      However, there was strong interest in gene testing regardless of the number of
      affected relatives, and persons with more affected relatives were generally
      willing to pay more for the gene test (up to $1000). CONCLUSIONS: The strength of
      family history of colon cancer is associated with risk perception but not with
      willingness to undergo gene testing.

PMID- 10207639
TI  - Attitudes toward colon cancer gene testing: factors predicting test uptake.
AB  - OBJECTIVES: Genetic discoveries in hereditary nonpolyposis colorectal cancer
      (HNPCC) have made possible genetic testing to determine susceptibility to this
      form of colorectal cancer (CRC). This study measured the uptake of genetic
      testing for HNPCC among first-degree relatives of CRC patients and conducted a
      preliminary analysis of the predictors of test uptake. MATERIALS AND METHODS: We
      compared 77 test acceptors and 181 decliners on demographic, medical history, and
      psychological characteristics, controlling for distance from the testing center.
      The psychological factors studied were risk perception for CRC, frequency of
      cancer thoughts, and perceived ability to cope with unfavorable genetic
      information. RESULTS: In the final regression model, after accounting for all
      variables, the significant predictors of test uptake were increased risk
      perception, greater perceived confidence in ability to cope with unfavorable
      genetic information, more frequent cancer thoughts, and having had at least one
      colonoscopy. The association between risk perception and uptake was dependent on
      frequency of cancer thoughts. Among those who thought about getting CRC more
      often, the probability of testing increased as perceived risk increased to
      approximately 50% likelihood of getting CRC and then leveled off. In contrast,
      among those who never or rarely thought about getting CRC, risk perception was
      unrelated to testing decision. CONCLUSIONS: Our findings are consistent with the
      associations reported between psychological factors and other cancer screening
      behaviors.

PMID- 10207640
TI  - Intention to learn results of genetic testing for hereditary colon cancer.
AB  - INTRODUCTION: This report investigates the correlates of intention to find out
      genetic test results in colorectal cancer patients undergoing genetic counseling
      and testing for hereditary nonpolyposis colon cancer. Specifically, we
      investigated whether intention to learn genetic test results was associated with
      sociodemographic factors, medical history, psychosocial factors, attitudes,
      beliefs, and decisional considerations related to genetic testing. MATERIALS AND
      METHODS: Among 342 colorectal cancer patients who went through an informed
      consent process and gave blood for genetic testing and who were eligible for a
      psychosocial questionnaire study, 269 cases completed a baseline interview.
      Patients were contacted in person during a routine clinic visit or by letter and
      follow-up telephone call and were interviewed either in person or by telephone.
      RESULTS: In univariate analysis, intention to learn test results was positively
      associated with income, quality of life, a belief that being tested will help
      family members prevent cancer, being worried about carrying an altered gene, and
      a belief that one has the ability to cope with test results. It was negatively
      associated with a belief that genetic counseling is too much trouble relative to
      the benefits. Intention also was positively associated with scales measuring the
      pros of learning test results and the pros of informing relatives about test
      results; it was negatively associated with the cons of learning test results. In
      multivariable analysis, the belief that testing would help family members prevent
      cancer, being worried about carrying an altered gene, and the pros of learning
      test results remained statistically associated with intention when other
      variables were included in the model. CONCLUSIONS: Our findings showed that the
      positive aspects of genetic testing were more strongly associated with intention
      than were the negative aspects. They also showed that persons who stated an
      intention to learn their genetic test results were more likely than persons who
      did not to affirm both the benefits and the importance of such testing. These
      results are consistent with the literature on psychosocial aspects of genetic
      testing for breast cancer.

PMID- 10207642
TI  - Attitudes and interest in genetic testing for breast and ovarian cancer
      susceptibility in diverse groups of women in western Washington.
AB  - OBJECTIVES: This paper examines the knowledge, opinions, and predictors of
      interest in genetic testing for breast cancer risk in a demographically diverse
      group of women in western Washington who participated in a randomized controlled
      trial (RCT) of breast cancer risk counseling methods. MATERIALS AND METHODS: Four
      groups of women were surveyed, all with some family history of breast cancer: (a)
      307 white women; (b) 36 African-American women; (c) 87 lesbian/bisexual women;
      and (d) 113 Ashkenazi Jewish women. As part of the baseline questionnaire for the
      RCT, participants were asked about their familiarity with genetic testing for
      breast cancer risk, their interest in such testing and opinions of it, and
      actions they anticipated based on test results. RESULTS: Women in all four groups
      favored ready access to testing, believed the decision to be tested should be a
      personal choice, believed that genetic test results should stay confidential, and
      were not greatly concerned that this might not be possible. Women anticipated
      using such genetic test results to increase the frequency of various breast
      cancer screening methods (in all four groups, > 69% would increase mammogram
      frequency, > 85% would increase clinician exam, and > 92% would increase breast
      self exam). Women overwhelmingly rejected prophylactic surgery as a preventive
      measure (in all > 80% probably or definitely would not consider it). Significant
      predictors of interest in genetic testing for cancer risk included perceived
      risk, cancer worry, and beliefs about access to testing. CONCLUSIONS: These data
      will be of interest to health care providers, payers, public health
      professionals, legislators, and others as they consider issues associated with
      population testing for susceptibility to common diseases such as breast cancer.

PMID- 10207641
TI  - Racial differences in testing motivation and psychological distress following
      pretest education for BRCA1 gene testing.
AB  - OBJECTIVES: We conducted a randomized trial to investigate racial differences in
      response to two alternate pretest education strategies for BRCA1 genetic testing:
      a standard education model and an education plus counseling (E + C) model.
      MATERIALS AND METHODS: Two hundred twenty-eight Caucasian women and 70 African
      American women with a family history of breast or ovarian cancer were contacted
      for a baseline telephone interview to assess sociodemographic characteristics,
      number of relatives affected with cancer, and race before pretest education.
      Outcome variables included changes from baseline to 1-month follow-up in cancer
      related distress and genetic testing intentions, as well as provision of a blood
      sample after the education session. RESULTS: African American women were found to
      differ significantly from Caucasian women in the effects of the interventions on
      testing intentions and provision of a blood sample. Specifically, in African
      American women, E + C led to greater increases than education only in intentions
      to be tested and provision of a blood sample. These effects were independent of
      socioeconomic status and referral mechanisms. In Caucasian women, there were no
      differential effects of the interventions on these outcomes. Reductions in cancer
      specific distress were evidenced in all study groups. However, this decrease,
      although not significantly different, was smallest among African American women
      who received E + C. CONCLUSIONS: In low- to moderate-risk African American women,
      pretest education and counseling may motivate BRCA1 testing. Further research is
      needed to explore the mechanisms of impact of the alternate pretest education
      strategies and to increase the cultural sensitivity of education and counseling
      protocols.

PMID- 10207643
TI  - Participation in breast cancer susceptibility testing protocols: influence of
      recruitment source, altruism, and family involvement on women's decisions.
AB  - OBJECTIVES: We offered education, counseling, and family-based BRCA1/2 testing to
      women at increased risk of breast cancer and assessed (a) their reasons for
      participating and (b) whether source of recruitment, desire to help research
      (altruism), and the need to communicate with their affected relative about
      testing distinguish those who did and those who did not complete each phase of
      our protocol. MATERIALS AND METHODS: We sent invitations to 403 women who had
      completed a questionnaire on BRCA1/2 testing, 178 of whom were considered high
      risk because they had more than one relative on the same side of the family with
      early-onset breast cancer. RESULTS: Among the 132 high-risk respondents from the
      mid-Atlantic states (where testing was offered), 36% (n = 47) were interested in
      counseling. Those who actually attended counseling were more likely to have some
      college education, a higher perceived risk of breast cancer, and a greater fear
      of stigma and were less likely to have a daughter than those who did not attend.
      The reasons for attending that were rated "very important" were to learn about
      the test (80%), to have the test (43%), and to help research (38%). High-risk
      women were eligible for testing only if their affected relative was willing to be
      tested and tested positive. After the session, 83% intended to ask their affected
      relative to be tested, but only half of the affected relatives actually came for
      pretest counseling. The proportion of participants who ultimately involved an
      affected relative was 2.5 times higher among women from a clinical population
      (25%) than among those from a registry population (10%); in this latter
      population, an altruistic desire to help research was a greater motivator for
      participation than interest in being tested. CONCLUSIONS: Source of recruitment
      influences both motivations to attend education and counseling and actual testing
      behavior. These results have implications for interpretation of findings from
      studies in research settings as well as for informed consent and decision-making
      in the context of family-based testing.

PMID- 10207644
TI  - Familial context of genetic testing for cancer susceptibility: moderating effect
      of siblings' test results on psychological distress one to two weeks after BRCA1
      mutation testing.
AB  - OBJECTIVES: To determine whether psychological distress differs among individuals
      tested for a BRCA1 mutation and is moderated by the pattern of their siblings'
      test results. MATERIALS AND METHODS: Participants in this study are members of a
      large kindred identified with a BRCA1 mutation. Subjects included 87 males and
      125 females who completed a baseline interview, were tested for a BRCA1 gene
      mutation, received their results in person from a genetic counselor, completed a
      follow-up interview 1-2 weeks after the receipt of their test results, and had
      complete data on all variables used in the analysis. The main outcome of the
      study was psychological distress as measured by the Impact of Event Scale during
      the 1-2 week follow-up interview. Data were analyzed based on multiple
      regression. RESULTS: Male carriers, relative to noncarriers, experienced
      significantly more distress if they were the first tested than when all of their
      tested siblings were already known to be negative. Noncarrier males whose
      siblings all tested positive also encountered significant test-related distress.
      The largest adverse psychological consequences for female carriers, relative to
      noncarriers, were for those who were tested first and those whose tested siblings
      were noncarriers. CONCLUSIONS: The familial context in which genetic testing is
      conducted may be important for understanding how individuals react to their own
      test results.

PMID- 10207645
TI  - Exploring family relationships in cancer risk counseling using the genogram.
AB  - OBJECTIVES: The genogram is a tool that has facilitated counseling in family
      therapy and social work for many years. It is hypothesized that genograms may
      also be useful in genetic counseling, because they help the counselor to acquire
      more objective and consistent information from the client, as well as to
      incorporate family dynamics and psychosocial issues into the counseling approach.
      MATERIALS AND METHODS: A pilot study of genograms used as an adjunct to genetic
      counseling was performed at Fox Chase Cancer Center's Family Risk Assessment
      Program. A questionnaire was developed to elicit genograms from 38 women at risk
      for familial breast and/or ovarian cancer. After standard pedigree expansion, a
      series of questions was asked about the consultand's relationship with other
      family members, communication patterns within the family, attitudes toward
      genetic testing, family reactions to cancer, roles individuals play in the
      family, and significant historical or anniversary events. Relationships were
      defined by the consultand as close, very close, conflictual, fused and
      conflictual, distant, or estranged. RESULTS: The majority of relationship types
      reported by 38 individuals was "very close" or "close." Eighty-one % reported
      having close/very close relationships with their spouses, 83% reported close/very
      close relationships with their mothers, and 70% reported close/very close
      relationships with their fathers. The degree of familial cohesion as depicted by
      the genogram correlates positively with scores obtained on the standardized
      Social Adjustment Scale Self-Report (P = 0.01). CONCLUSIONS: Given the family
      wide implications of genetic testing, the genogram may offer important guidance
      in family-targeted interventions.

PMID- 10207646
TI  - Real-time interactive simulator for percutaneous coronary revascularization
      procedures.
AB  - This article describes the simulation of real-time catheter navigation in our
      interactive interventional cardiology simulation system (ICard). ICard is
      designed to enable medical students or physicians to familiarize themselves with
      the techniques of interventional catheterization procedures. The ICard software
      provides three-dimensional (3-D) views of the blood vessels and fluoroscopic
      images for real-time visualization of the catheter position. The 3-D human
      vasculature is built from various image data sets and is represented with a
      central line hierarchy model. Navigation of the catheter and guide wire and their
      interaction with blood vessels are implemented by applying the finite element
      method. Physical modeling that features the elasticity of the catheter and guide
      wire was developed to provide a realistic simulation of catheterization
      procedures. An electromechanical device was also developed in the system,
      allowing physical manipulation of catheter and guide wire movements. ICard can be
      used for training and design of equipment for interventional cardiology and may
      be further extended for pretreatment planning.

PMID- 10207647
TI  - Deformable modeling of facial tissue for craniofacial surgery simulation.
AB  - While deformable object modeling has been studied by computer graphics
      specialists for more than two decades, only a few applications in the field of
      surgical simulation have been developed which provide both real-time and
      physically realistic modeling of complex, nonlinear tissue deformations.
      Particularly in craniofacial surgery, the prediction of soft-tissue changes-
      which result from alterations in the underlying bone structure--is critical to
      the surgical outcome. The prediction these tissue changes and, therefore, the
      prognosis of the postoperative appearance of the patient, is still based on
      empirical studies of the relationship between bone and tissue movements: There
      exists no physical model which takes into account the individual patient anatomy
      to simulate the resulting tissue changes during craniofacial surgery. In this
      article we present two different deformable tissue models which are intergrated
      in an interactive surgical simulation test bed. Both techniques allow precise
      preoperative simulation of the resulting soft tissue changes during craniofacial
      surgery and visualization of the patient's postoperative appearance. The
      different deformable models are described in detail and both are applied to the
      same craniofacial case study. The simulation results are shown and compared with
      regard to the speed and accuracy of the prediction of the patient's postoperative
      appearance.

PMID- 10207648
TI  - Augmented reality visualization system for intravascular neurosurgery.
AB  - We aimed to construct an augmented reality-based visualization system to support
      intravascular neurosurgery and evaluate it in clinical environments. Three
      dimensional (3D) vascular models are overlaid on motion pictures from X-ray
      fluoroscopy by 2D/3D registration using fiducial markers. The models are
      reconstructed from 3D data obtained from X-ray computed tomographic angiography
      or from magnetic resonance angiography using the marching-cube algorithm.
      Intraoperative X-ray images are mapped as texture patterns on a screen object
      which is displayed with the vascular models. Distortion of X-ray fluoroscopy is
      eliminated by a new technique of screen mesh deformation. A quantity called
      reprojection distance was introduced to evaluate the reliability of the displayed
      images. It predicts the maximum registration error around the registered objects.
      Analyses of reprojection distances were performed using synthetic data consisting
      of marker coordinates with 2D or 3D errors. The tolerance of reprojection
      distance for the clinical environment was determined to be 3.0 mm. The system was
      tested in two clinical cases in which reprojection distances of 2.6 and 2.09 mm
      were obtained. Construction and evaluation of our prototype system were
      successfully carried out. Further development is planned employing a range sensor
      to permit markerless registration.

PMID- 10207649
TI  - Stereolithography versus milled three-dimensional models: comparison of
      production method, indication, and accuracy.
AB  - Computed tomography (CT) based three-dimensional (3-D) lifelike models have
      proved to be of great value, especially in craniomaxillofacial surgery. They
      improve and facilitate diagnosis, therapeutic planning, model operations, and
      definitive treatment in tumor surgery, traumatology, dysgnathia, alveolar
      atrophy, and congenital and asymmetrical malformations. From 1988 to 1998, 760
      stereolithography (STL) and milled 3-D models were employed in our department.
      These two production methods have become the msot commonly used approaches, and
      the question as to which is preferable is the subject of controversy in the
      literature. Using two test models the STL and the milling method were compared
      with regard to production method and accuracy, and the resulting differences in
      indications for their use are discussed. The limiting factor for increased
      accuracy is the distance between each pair of CT scans. Milled models show a
      higher precision compared to STL models within the CT-scan plane, but the more
      the measurements deviate from this plane (becoming oblique) the more inaccurate
      the data becomes. STL exhibits greater deviations, but the inaccuracy is randomly
      distributed. The mean variation from the original was 0.81 mm for STL and 0.54 mm
      for milled models. Although 90% of the milled and 80% of the STL values are
      within a deviation of +/- 1 mm, it should be noted that maximum deviations of
      3.15 mm in milled models and 2 mm in STL have been shown. Both methods are
      sufficiently accurate for clinical use. In standard cases involving the upper and
      lower jaw, malar bone, orbita, and calvaria the shorter production time and lower
      costs make milled models preferable. In special cases, in which hollows and fine
      structures play a major role (e.g., those involving the skull base, paranasal
      sinuses, inner ear, and mandibular canal), STL is indicated.

PMID- 10207650
TI  - Optical high-precision three-dimensional position measurement system suitable for
      head motion tracking in frameless stereotactic radiosurgery.
AB  - Head motion is a significant source of therapy-effect degradation in frameless
      stereotactic radiosurgery (SRS). In this study, a three-dimensional (3-D) optical
      head motion measurement system and a coordinate transformation algorithm were
      used to track patient head motion. With this system, head motion in frameless SRS
      was carefully investigated with a precision of < 0.1 mm. Head motions without any
      restraint (three cases) and with a Laitinen adapter (four cases) were measured
      with a data sampling rate of once per second for 30 min. Positions of IR light
      emission diode markers attached to the head were analyzed by two statistical
      methods. From these data, mathematically simulated head motions were obtained in
      each of the three coordinate directions for nonrestraint and Laitinen-adapter
      SRS. The results show that segmenting a frameless SRS procedure into a sequence
      of short intervals and repeating registration of the target position for each
      interval is a good strategy for better therapy precision. This optical 3-D
      position measurement system is suitable for high-precision head motion tracking
      in frameless SRS.

PMID- 10207651
TI  - Virtual pancreatoscopy of mucin-producing pancreatic tumors.
AB  - We used computer-based virtual endoscopy techniques as a novel approach to
      clarify the three-dimensional (3D) surgical anatomy of the pancreas and of mucin
      producing pancreatic tumors. Thirteen cases (18 lesions) of mucin-producing
      pancreatic tumors were investigated by virtual pancreatoscopy. Virtual endoscopic
      images were generated with virtual endoscopy software application on UNIX
      workstations. We created surface-rendered virtual endoscopic images derived from
      a computer reconstruction of the cross-sectional magnetic resonance imaging data.
      Virtual endoscopy could visualize the surfaces of the pancreatic duct and the
      bile duct, and also demonstrated all cystic tumors. The surfaces of malignant
      mucin-producing pancreatic tumors were illustrated as being more irregular than
      those of benign lesions. The virtual endoscopic technique could demonstrate not
      only a surface-rendered endoscopic image of the tumors but also a 3D
      reconstructed image of the pancreas. The relationship to anatomic structures
      located outside the surfaces is continuously maintained and displayed at the same
      time. Virtual pancreatoscopy was useful for surgical planning of minimally
      invasive resection of the pancreas.

PMID- 10207652
TI  - Computational analysis of platelet adhesion and aggregation under stagnation
      point flow conditions.
AB  - The clinical relevance of platelet function assessment with stagnation point flow
      adhesio-aggregometry (SPAA) has been verified. Quantitative analysis of platelet
      adhesion and aggregation is possible by means of mathematical analysis of the
      dark-field, light intensity curves (growth curves) obtained during the SPAA
      experiment. We present a computational procedure for evaluating these curves,
      which was necessitated by, and is based on, actual clinical application. A
      qualitative growth curve classification, corresponding to a basic and distinct
      pattern of platelet deposition and characteristic of a regularly occurring
      clinical state is also presented.

PMID- 10207653
TI  - A three-dimensional model for arterial tree representation, generated by
      constrained constructive optimization.
AB  - The computational method of constrained constructive optimization (CCO) has been
      generalized in two important respects: (1) arterial model trees are now grown
      within a convex, three-dimensional piece of tissue and (2) terminal flow
      variability has been incorporated into the model to account for the heterogeneity
      of blood flow observed in real vascular beds. Although no direct information from
      topographic anatomy enters the model, computer-generated CCO trees closely
      resemble corrosion casts of real arterial trees, both on a visual basis and with
      regard to morphometric parameters. Terminal flow variability was found to induce
      transitions in the connective structure early in the trees' development. The
      present generalization of CCO offers--for the first time--the possibility to
      generate optimized arterial model trees in three dimensions, representing a
      realistic geometrical substrate for hemodynamic simulation studies. With the
      implementation of terminal flow variability the model is ready to simulate
      processes such as the adaptation of arterial diameters to changes in blood flow
      rate or the formation of different patterns of angiogenesis induced by changing
      needs of blood supply.

PMID- 10207655
TI  - Automatic karyotyping of metaphase cells with overlapping chromosomes.
AB  - Image analysis research aimed at analyzing images of banded, human chromosomes is
      described. An experimental automated karyotyping system (AKS) has been assembled.
      The goal of the system is to label the chromosomes from a metaphase image with
      minimal human intervention. The AKS is unique in that it is designed to
      automatically process cells containing overlapping chromosomes. It also has four
      novel algorithmic features: the use of cross section sequence graphs, an over
      segmentation-based segmentation strategy, the use of the 'pale path' concept for
      banded chromosomes and the application of mathematical programming for cell-level
      chromosome classification in cells with overlapping chromosomes. System
      performance was analyzed using a variety of metaphase images exhibiting various
      levels of overlapping chromosomes.

PMID- 10207654
TI  - Pathogenic mechanisms in ischemic damage: a computational study.
AB  - The pathogenesis of penumbral tissue infarction during acute ischemic stroke is
      controversial. This peri-infarct tissue may subsequently die, or survive and
      recuperate, and its preservation has been a prime goal of recent therapeutic
      trials in acute stroke. Two major hypotheses currently under consideration are
      that penumbral tissue is recruited into an infarct by cortical spreading
      depression (CSD) waves, or by a non-wave self-propagating process such as
      glutamate excitotoxicity (GE). Careful experimental attempts to discriminate
      between these two hypotheses have so far been quite ambiguous. Using a
      computational metabolic model of acute focal stroke we show here that the spatial
      patterns of tissue damage arising from artificially induced foci of infarction
      having specific geometric shapes are inherently different. This is due to the
      distinct propagation characteristics underlying self-regenerating waves and non
      wave diffusional processes. The experimental testing of these predicted spatial
      patterns of damage may help determine the relative contributions of the two
      pathological mechanisms hypothesized for ischemic tissue damage.

PMID- 10207656
TI  - Exact 95% confidence intervals for differences in binomial proportions.
AB  - A method is described that allows exact 95% confidence intervals to be computed
      for differences in binomial proportions. The method itself is not iterative, but
      it uses the iteratively computed 95% confidence intervals for the individual
      binomial proportions. The method converges with the usual normal approximation
      method, as denominators become large. It correlates very closely with the Yates
      corrected chi-square test. The method works regardless of the definition of
      success or failure in the proportions and regardless of the order of the
      proportions.

PMID- 10207657
TI  - Improving interorganizational data interchange for drug development.
AB  - This paper presents a reengineered process that uses a markup language to do
      interorganizational data interchange between the participants in the US drug
      development process. The two major goals of this paper are to present (1) a
      detailed enough description of the reengineered version of this process that a
      practitioner will be able to use it and (2) a case-study of the reengineering of
      an interorganizational data interchange system that is applicable to other areas
      in health care. The detailed description is augmented with a companion web-site
      that shows all programs in a working prototype. The case-study uses an IDEF0
      model to show the structure of benefits from markup standards for
      interorganizational data interchange.

PMID- 10207658
TI  - Gender differences in the rate of comorbid axis I disorders in depressed
      outpatients.
AB  - We examined gender differences in comorbid Axis I disorders in 236 outpatients
      with major depression. Axis I comorbidity, age of onset of depression and
      comorbid disorder were assessed with the SCID-P. Depression severity was assessed
      with the HAM-17. The results indicated that males had a higher rate of comorbid
      substance abuse/dependence, while females had a higher rate of comorbid bulimia
      nervosa. These results are consistent with previous research, with the marked
      exception that females did not have higher rates of anxiety disorders in general,
      and in particular, panic disorder, simple and social phobia, obsessive-compulsive
      disorder and agoraphobia. It is concluded that the female predominance in anxiety
      disorders found in general population studies may be due to comorbidity with
      depression.

PMID- 10207659
TI  - Double-blind comparison of citalopram and placebo in depressed outpatients with
      melancholia.
AB  - This multicenter study compared the efficacy and safety of citalopram and placebo
      in a population of moderately to severely depressed patients with melancholia.
      This randomized, double-blind, parallel-group study compared citalopram (flexible
      dose; 20-80 mg/day) with placebo in 180 psychiatric outpatients with a DSM-III
      diagnosis of major depression or bipolar disorder, depressed, who also met DSM
      III criteria for melancholia. Following a 1-week placebo washout period, patients
      meeting study entry criteria were randomized to 4 weeks of double-blind treatment
      with either citalopram or placebo. Efficacy measures included the Hamilton Rating
      Scale for Depression (HAM-D), the Clinical Global Impressions (CGI) Scale, and
      the Zung Self-Rating Depression Scale. Patients treated with citalopram showed
      significantly greater improvement at endpoint than placebo patients on the HAM-D,
      CGI, and Zung scales. On the HAM-D, citalopram patients exhibited significantly
      greater improvement than placebo patients after 1 week of double-blind treatment
      and at all subsequent study visits. Endpoint analyses of the HAM-D subscales
      demonstrated that citalopram produced significant improvement of the psychomotor
      retardation, cognitive disturbance, sleep disturbance, and melancholia symptom
      clusters. Nausea, dry mouth, somnolence, dizziness, and increased sweating were
      reported at higher rates by citalopram-treated patients than by placebo-treated
      patients, but there were no significant citalopram-placebo differences in the
      incidence of activation (e.g., anxiety, nervousness, insomnia) or sexual
      dysfunction. Analysis of electrocardiograms, vital signs, and laboratory tests
      did not reveal any clinically significant effects of citalopram treatment. The
      results of this study indicate that citalopram is safe and effective in the
      treatment of depressed patients with melancholia, and is associated with a
      favorable side effect profile and a potentially rapid onset of action.

PMID- 10207660
TI  - Physical health problems in depressed and nondepressed children and adolescents
      of parents with opiate dependence.
AB  - The increased risk of physical health problems in adult depressed patients has
      been shown in numerous studies. A recent study of the offspring of depressed
      parents found similar associations. The purpose of this study is to examine the
      strength and specificity of the association between depression and physical
      health problems in children and adolescents whose parents are dependent upon
      opiates. The sample consisted of offspring ages 6-17 (mean age 11 years) of
      opiate addicts who had a history of major depressive disorder (MDD; n = 28);
      other mood disorders (n = 31); no history of mood disorders but other psychiatric
      disorders (n = 92); or no history of psychiatric disorder (n = 127). Detailed
      psychiatric assessment and medical history of the offspring by direct interview
      with the offspring and an informant were obtained blind to parental diagnosis.
      After controlling for possible confounders, there was an increased risk of
      dermatological disorders, headache, other neurological/neuromuscular disorders,
      bronchitis, other respiratory disorders and hospitalizations for nonsurgical
      procedures in offspring with MDD, as compared to nonpsychiatrically ill controls.
      The offspring with other mood disorders had a slightly elevated risk. Major
      depression in children and adolescents whose parents are dependent on opiates is
      associated with increased risk of physical health problems. This finding is
      consistent with other reports and the timing of the physical health problems
      requires further study.

PMID- 10207661
TI  - Double-blind comparison of fluoxetine and desipramine in the treatment of
      depressed women with advanced HIV disease: a pilot study.
AB  - A double-blind, placebo-controlled study was conducted to assess the relative
      efficacy and tolerability of fluoxetine and desipramine in depressed, human
      immunodeficiency virus (HIV)-positive women. Although difficulty in the
      recruitment and retention of participants led to insufficient power to detect
      differences between treatment groups, results indicated that participants
      experienced improvement in their depression. However, for most women, significant
      depressive symptoms remained after 6 weeks of treatment. In addition, although
      most participants reported at least one adverse event after treatment began, most
      of the side effects, regardless of treatment condition, were mild to moderate in
      severity. Important barriers to study participation and completion are discussed,
      as well as suggestions for increasing the involvement of depressed, HIV-positive
      women in future treatment studies.

PMID- 10207662
TI  - Depressed patients who suicide at their first attempt have had few admissions.
AB  - A prior suicide attempt is generally considered to be an indicator of increased
      future suicide risk. However, approximately 50% of psychiatric patients who
      commit suicide have made no previous suicide attempt. Thus, an effort was made to
      detect other predictors of future suicide risk in this group. The records of 100
      psychiatric patient suicides were examined. Patients who completed suicide at
      their first attempt (n = 57) were compared with patients who suicided after a
      previous attempt (n = 43). There were no significant differences between the two
      groups on any of the sociodemographic or clinical variables examined. However,
      patients with a primary psychiatric diagnosis of an effective disorder who
      committed suicide at their first attempt had had significantly less admissions
      than depressed patients who committed suicide after a previous attempt. The
      clinical implication is that the absence of many prior admissions in a depressed
      patient is not an indicator of low suicide risk.

PMID- 10207663
TI  - Fluoxetine and sertraline dosages in major depression.
AB  - In a retrospective study, we sought to determine medication dosages usually
      prescribed to obtain euthymia in 59 outpatients with a diagnosis of major
      depression treated with fluoxetine or sertraline. Charts of veterans admitted to
      the outpatient mental health clinic at the West Los Angeles Veterans Hospital
      with a diagnosis of major depression and treated with either fluoxetine or
      sertraline were reviewed. Progress notes were analyzed for a 6-month time period
      after the initiation of the medication treatment, and improvement was rated by a
      physician blind to the drug used for treatment. No significant differences were
      found in overall response rates between the fluoxetine (81% responders) and
      sertraline (76% responders) groups. Eighty-one percent of the fluoxetine
      responders compared to 32% of sertraline responders were at the manufacturer's
      recommended starting dose (MRSD) at the time of clinical response. One-third of
      patients receiving sertraline were started on or rapidly titrated to more than 50
      mg/day. When only those patients receiving an adequate trial of sertraline at 50
      mg were considered, 47% required a dose increase to achieve a remission. These
      data suggest that 50 mg of sertraline may be inadequate for some patients to
      achieve a resolution of symptoms of major depression and that many clinicians
      currently prescribe in a manner suggesting that they believe the MRSD is a
      suboptimal dosage.

PMID- 10207664
TI  - Summer mood in winter depressives: validation of a structured interview.
AB  - Two structured interviews, the Hypomania Interview Guide (Including Hyperthymia),
      for Seasonal Affective Disorder (HIGH-SAD) and its successor, the Hypomania
      Interview Guide (Including Hyperthymia), Retrospective Assessment Version (HIGH
      R), were validated for the assessment of nondepressed spring/summer mood states
      in patients with DSM-III-R or DSM-IV diagnoses of Recurrent Bipolar disorder (I,
      II or NOS) or Recurrent Major Depressive Disorder (MDD; unipolar), both with
      Seasonal Pattern, and in normal control subjects (HIGH-SAD only). The instruments
      retrospectively rate the frequency and severity of DSM diagnostic criterion
      features as well as several non-DSM features. Both instruments had high internal
      consistency. Normal controls had lower total scores than unipolar patients, who
      had lower scores than bipolar patients. Total score classified 85-91% of patients
      with seasonal affective disorder (SAD) into the correct unipolar or bipolar
      group. For boundary mood cases, small subsets of features provided better
      classification accuracy. Based on total score, MDD patients were divided into
      three subgroups: euthymes (normal mood), hyperthymes (slightly elevated mood),
      and high-hyperthymes (scores overlapping with hypomania). With the exception of
      sharpened thinking, DSM items dominated patient classifications. Distinct
      clusters of "positive" (pleasant, agreeable) or "negative" (impairing) features
      described the mood states. The HIGH-R and HIGH-SAD are useful for discriminating
      and classifying hypomania and mania in bipolar patients, and euthymia and
      hyperthymia in unipolar patients.

PMID- 10207665
TI  - Hypomania interview guide (including hyperthymia): retrospective assessment
      version (HIGH-R).

PMID- 10207666
TI  - Diagnostic implications of albumin messenger RNA detection and cytokeratin
      pattern in benign hepatic lesions and biliary cystadenocarcinoma.
AB  - Cytokeratin (CK) patterns and albumin messenger RNA (mRNA) are investigated in 24
      patients with benign hepatic lesions (7 patients with focal nodular hyperplasia
      [FNH], 10 with hepatocellular adenomas [HA], 1 with biliary hamartoma, 4 with
      biliary cysts, 2 with cystadenomas) and in 8 patients with cystadenocarcinoma, a
      rare liver malignancy. The lesions and surrounding tissue of the hepatocytic
      components expressed CK 8 and 18 at immunohistochemistry, whereas the biliary
      elements evidenced CK 8 and 18 and CK 7 and 19. The albumin mRNA, as detected by
      in situ hybridization (ISH), revealed different distributions in the hepatocytes
      of FNH and HA. In the benign biliary lesions, the normal hepatocytes surrounding
      the tumors expressed albumin mRNA, whereas the biliary structures did not.
      Interestingly, in the cystadenocarcinomas, albumin mRNA was observed not only in
      the hepatocytes of residual parenchyma, but also in neoplastic bile duct cells
      lining the carcinomatous cysts; no signal was identified in the nonneoplastic
      biliary elements. This indicates that cystadenocarcinomas have a mixed biological
      phenotype and suggests they could arise either from pluripotent cells or from
      neoplastic cells that reacquire epigenetic features. Our results suggest two
      possible diagnostic applications for albumin ISH: on routine sections, it could
      represent an important tool for distinguishing between cystadenoma and
      cystadenocarcinoma; and on fine needle biopsy specimens, it could reduce
      uncertainty between FNH and HA.

PMID- 10207667
TI  - Molecular assessment of clonality leads to the identification of a new germ line
      TP53 mutation associated with malignant cystosarcoma phyllodes and soft tissue
      sarcoma.
AB  - Cystosarcoma phyllodes (CSP) is a rare breast neoplasm composed of stromal and
      epithelial elements. It usually runs a benign course but it may metastasize. In a
      31-year-old patient with recurring CSP, a mesenchymal tumor in the leg developed.
      The question arose whether the latter tumor could be a metastasis from the CSP,
      which would have major treatment consequences. The problem was addressed using
      molecular methods, i.e., comparison of the pattern of polymorphic repeat markers
      on chromosome 17p as well as single strand conformation polymorphism analysis and
      sequencing of exons 5 to 8 of the TP53 gene in both tumor and normal tissue. An
      identical pattern of loss of heterozygosity in both breast tumors was
      demonstrated, but a different pattern was shown in the tumor in the leg. This led
      to the conclusion that the latter tumor had to be a new primary tumor. A mutation
      in codon 162 of the TP53 gene was found in the tumor tissue as well as in the
      normal tissue of this patient. This germ line mutation leads to the replacement
      of isoleucine by asparagine and most likely has functional consequences. In all
      four examined tumors of this patient, the normal TP53 allele was lost. This is
      strong evidence that this germ line TP53 mutation causes the genesis of these two
      rare primary mesenchymal tumors in this young patient. The current study
      exemplifies the power of molecular diagnostic methods in investigating the
      specific clinical problem of clonal relation between two separate tumors. The
      germ line mutation found in codon 162 of the TP53 gene and the association with
      cystosarcoma phyllodes have not been described previously.

PMID- 10207668
TI  - Preservation of nucleic acids for polymerase chain reaction after prolonged
      storage at room temperature.
AB  - A guanidinium isothiocyanate (GITC) lysis solution was evaluated for its efficacy
      in preserving nucleic acids for subsequent analysis after prolonged storage at
      room temperature. Aliquots of thyroid crude cell lysates were stored at 22
      degrees C for 8 weeks in the GITC solution. Crude cell lysates stored for 2 weeks
      in the GITC solution consistently provided adequate RNA and DNA for reverse
      transcriptase-polymerase chain reaction (RT-PCR) and PCR, respectively, of beta 2
      microglobulin, thyroid stimulating hormone receptor (TSHR), and thyroglobulin.
      Interestingly, the thyroglobulin and TSHR messages from thyroid fine needle
      aspirate samples were detected by RT-PCR only when stored at room temperature for
      less than 1 week, whereas the RT-PCR product for beta 2-microglobulin was
      detectable in 95% of the samples at 3 months. In addition, thyroglobulin DNA was
      amplified by PCR in nearly all samples stored at 22 degrees C for 2 months. These
      data suggest that GITC solutions can be used to preserve nucleic acids in most
      circumstance until transported to laboratories equipped and staffed with
      appropriate resources.

PMID- 10207669
TI  - Multiplex polymerase chain reaction for rapid detection of atypical mycobacteria
      and Mycobacterium tuberculosis complex.
AB  - A three-step polymerase chain reaction (PCR) method was developed for the
      detection and typing of mycobacterial DNA in clinical samples and fixed tissue
      specimens. The first step was to rule out or prove the presence of DNA of
      Mycobacterium tuberculosis complex. An amplified fragment from the insertion
      sequence (IS) 6110 was used for this purpose. Patients negative for IS 6110 were
      evaluated for a fragment of the 65 kDa-antigen, present in all mycobacteria. In
      positive patients, a multiplex PCR was performed for M. gordonae, M. avium, M.
      kansasii, M. fortuitum, and M. malmoense, combined in one PCR run. As another
      control, to prove mycobacterial DNA, PCR was used for the gene coding for the 16S
      ribosomal RNA also found in all mycobacteria. Appropriate negative controls were
      included. Different clinical samples were compared for an efficient amplification
      of these different mycobacterial DNA fragments. Different mycobacteria can be
      identified within one day in either unfixed cytologic and bacteriologic samples,
      or formalin-fixed paraffin-embedded tissue samples. Therefore, this method is a
      quick, cost efficient, and reliable tool to identify mycobacteria other than the
      tuberculosis complex.

PMID- 10207671
TI  - Uterine cervical dysplasia and cancer: identification of c-myc status by
      quantitative polymerase chain reaction.
AB  - The c-myc oncogene status was determined in patients with nondysplasia (ND; 9
      patients), low-grade squamous intraepithelial lesion (LGSIL; 12 patients), high
      grade squamous intraepithelial lesion (HGSIL; 21 patients) and invasive squamous
      cell carcinoma (ISCC; 20 patients) of uterine cervix using fluorescent
      quantitative polymerase chain reaction (PCR). In the same paraffin-embedded
      specimens, other potential risk factors were also screened: human papillomavirus
      (HPV) infection, Ha-ras codon 12 mutation, DNA aneuploidy. Gene amplification,
      identified as c-myc copy numbers greater than the mean value +2 SD of patients
      with ND, was seen in 44% patients with LGSIL, 76% patients with HGSIL, and 67%
      patients with ISCC. These data indicate that c-myc amplification is one of the
      critical early events in the progression of uterine cervical lesions. HPV
      infection of various subtypes was identified in 0% patients with ND, 55% patients
      with LGSIL, 95% patients with HGSIL, and 84% patients with ISCC. No codon 12
      mutation of the Ha-ras gene was found in this series. Aneuploid DNA pattern was
      seen in 0% patients with ND, 58% patients with LGSIL, 90% patients with HGSIL,
      and 80% patients with ISCC. There was a significant correlation between HPV
      infection and DNA aneuploidy. However, no relationship was seen between c-myc
      status and other factors in this series. Patients with HGSIL and ISCC almost
      always (95%) had multiple risk factors, whereas more than half of the patients
      with LGSIL had no or only one risk factor (P = 0.0001).

PMID- 10207670
TI  - A two-tier polymerase chain reaction direct sequencing method for detecting and
      typing human papillomaviruses in pathological specimens.
AB  - An in-house polymerase chain reaction direct sequencing (PCR-DS) approach for HPV
      detection and typing was developed, taking advantage of two widely used pairs of
      human papillomavirus (HPV)-specific PCR primers, MY09/MY11 and GP5/GP6, and 33P
      labeled dideoxynucleotides. In this study, 105 pathological specimens were
      examined: 89% were diagnosed as cervical intraepithelial neoplasia (CIN) grade I
      III, 76.2% were HPV-positive by PCR-DS. The PCR using GP5/GP6 (first tier) and
      MY09/MY11 primers (second tier for the GP5/GP6-negative samples) detected
      additional 15%-25% HPV-positive samples compared with each pair used separately.
      Direct sequencing was then used to type the HPV. A readout of a sequence as short
      as 34 nucleotides within a specific region in the L1 gene is sufficient to type
      known or novel sequences. Because of its high sensitivity and cost-effectiveness,
      the two-tier PCR-DS was adopted by the authors as the current method of choice
      for HPV diagnosis with ultimate sequence precision.

PMID- 10207672
TI  - Detection of the source of mislabeled biopsy tissue paraffin block and
      histopathological section on glass slide.
AB  - The aim of this study was to identify the source of surgical biopsy tissue in
      paraffin block and histochemically stained biopsy section on a slide suspected to
      be mislabeled. Commercially available polymerase chain reaction (PCR)-based human
      lymphocyte antigen (HLA) DQA1 and Polymarker kits (Roche Molecular Systems,
      Branchburg, NJ, U.S.A.). were used to generate DNA profiles from biopsy tissue
      material in paraffin block and on histological slide, and the reference blood
      sample was collected from the patient. The source of biopsy tissue was detected
      by HLA DQA1 and polymarker profiling. Profiles obtained from biopsy material were
      consistent with those obtained from reference blood sample. The PCR-based DNA
      profiling techniques can determine the source of minute tissue in paraffin block
      and stained tissue sections on slides routinely prepared for diagnosis of
      carcinoma.

PMID- 10207673
TI  - Neurophysiological testing in long-standing cystinosis.
AB  - Neurophysiological data of two brothers with long-standing cystinosis are
      presented. Both patients showed a distally symmetrical myopathy affecting the
      arms more than the legs. Myopathy occurred before the onset of polyneuropathy or
      signs of central nervous involvement.

PMID- 10207674
TI  - The effect of jogging on P300 event related potentials.
AB  - Physical exercise has beneficial effects not only on cardiovascular system and
      fat metabolism, may also directly effect the cognitive process. We studied the
      effect of physical exercise on cognitive processes by measuring the P300 event
      related-potential (ERP) after jogging. Seven well-trained joggers were enrolled
      in this study and the P300 potentials using auditory oddball paradigm. ERPs were
      measured before and after 30 minutes of jogging. The amplitude of the P300
      significantly increased after jogging compared to values recorded before jogging.
      These findings suggest that jogging has the effect of facilitating cognitive
      processes involved in generation of the P300.

PMID- 10207675
TI  - Development of myasthenia gravis after interferon alpha therapy.
AB  - Interferon (IFN) alpha is now used in the treatment of some malignant diseases
      and chronic viral hepatitis. There have been several reports of development of
      autoantibodies and autoimmune diseases or the deterioration of preexisting
      disorders in patients under treatment. We enclose a case of myasthenia gravis
      (MG) which developed after six weeks of treatment as fluctuating bilateral
      ptosis, intermittent diplopia, and mild weakness of limb and neck muscles. A test
      dose of edrophonium chloride was administered, resulting in improved muscle
      strength. Elevated anti acetylcholine receptor (AChR) antibody titer was found.
      Single fiber electromyography showed an increased jitter from extensor digitorum
      communis, frequently accompanied by transmission blocking. Repetitive electric 3
      Hz stimulation of the abductor pollicis brevis muscle, revealed an abnormal
      decrement of 28% in compound motor action potential. Myasthenia gravis was
      diagnosed and the patient was given pyridostigmine, immunoglobulines and
      prednisone with benefit. Six months latter he developed an acute myasthenic
      crisis with severe respiratory failure and high anti AChR antibody titer. IFN
      alpha can induce MG or simply manifests a preexisting subclinical disease, but
      otherwise its therapeutic efficacy in MG has been shown in experimental and
      clinical studies. Autoimmune mechanisms, as the release of different cytokines as
      IFN, by immunocompetent cells, may be involved in the pathogenesis of both MG and
      chronic active hepatitis. Autoantibody production against postsynaptic membrane
      structures by IFN-alpha could be the underlying pathophysiology.

PMID- 10207676
TI  - Excitability recovery curves of blink reflexes in patients with athetotic
      cerebral palsy.
AB  - We evaluated the brainstem function or its excitability by the blink reflex
      evoked with the electrical stimulation to the supraorbital nerve in 10 patients
      with athetotic cerebral palsy compared with 10 normal subjects and 7 spastic type
      patients. There were no differences in stimulus intensity, latency of R1 and R2
      components, and duration and area of EMG activity of the R2 component of the
      blink reflex elicited by single stimulation among the two patients' groups and
      normal subjects. R1 recovery cycle to paired stimuli in the athetotic group
      showed a facilitation of the test responses by the conditioning stimuli at 100
      and 200 ms intervals, but were not significantly different from those in the
      normals. On the other hand, the R2 recovery curve in the athetotic group showed a
      significant hyperexcitability at all intervals from 100 to 600 ms compared to the
      normals. Our results from the R2 hyperexcitable recovery to paired stimuli are
      indicative of increased brainstem interneuronal excitability in athetotic
      patients and similar to the results reported in the disorders of the basal
      ganglia, i.e. Parkinson's disease, dystonia and blepharospasm. We suggest that
      this hyperexcitability might be caused by abnormal input possibly from the basal
      ganglia upon these brainstem interneurons.

PMID- 10207677
TI  - Macroemg in manifesting carriers of Duchenne muscular dystrophy.
AB  - The aim of present study was to analyse possible myopathic changes in the muscles
      of manifesting carriers of Duchenne Muscular Dystrophy (DMD) using concentric
      needle emg and macroemg methods. Our material consisted of 10 manifesting
      carriers aged 9-52 (mean 30 years) and 20 healthy age-matched females. Concentric
      needle emg (CNEMG) and macroemg was performed in biceps brachii (BB) muscle in
      both groups: carriers and controls. Myopathic changes were observed in BB muscle
      in 5 of 10 manifesting carriers using CNEMG and in all cases (10 carriers) using
      macroemg method. Macro electrode, which reflects total motor unit activity, i.e.,
      the total number and size of component muscle fibres, supplies information about
      early myogenic lesion of the muscle. Therefore the macroemg seems to be a
      sensitive and useful electrophysiological diagnostic method in carriers of DMD.

PMID- 10207678
TI  - Clinical significance of the F wave area in diabetic polyneuropathy.
AB  - OBJECTIVE: To investigate the electrophysiological significance of the abnormal F
      wave are (Farea) and its ratio (F/Marea) (%) to the corresponding M wave area
      (Marea) in patients with diabetic polyneuropathy (DP). MATERIALS AND METHODS: For
      tibial and peroneal nerves, the F/Marea and other F wave parameters (duration
      [Fdur], minimum latency [Fmin], amplitude [Famp]) were compared in 34 patients
      and age-matched controls. RESULTS: For controls, the Farea correlated with the
      Marea, but this was not found for DP patients. The peroneal F/Marea for DP
      patients was significantly larger than that for controls. For the both nerves,
      however, the F/Marea for DP patients was larger in nerves with a decreased Marea
      than those in nerves with a normal Marea and in the controls. An increased
      F/Marea was accompanied by prolonged Fdur. A decreased F/Marea was uncommon. The
      incidence of abnormal F/Marea was somewhat larger than that of abnormal F/Mamp,
      but smaller than the values for MCV and Fmin. CONCLUSIONS: The relationship
      between Farea and the Marea for DP patients differed from that of controls. An
      increased F/Marea was considered to reflect a denervation-reinnervation process
      or some central modification in firing of the anterior horn cells. Whereas
      amplitude of the F wave also reflect these electrophysiological conditions, the
      F/Marea is a little more sensitive than F/Mamp in detecting the abnormality.

PMID- 10207679
TI  - Study of central motor functions using magnetic stimulation in Parkinson's
      disease.
AB  - The pathophysiological abnormalities, the contribution of activity of
      facilitatory and inhibitory systems to muscle rigidity and hypokinesia in
      Parkinson's disease are not clarified in details. Transcranial magnetic
      stimulation of the motor cortex may provide useful data on the functional state
      of motor output of the central motor structures and on the functional condition
      of the intracerebral motor network. The abnormalities of the central motor
      functions and the modifying effect of L-dopa treatment in Parkinson's disease are
      the objectives of our study. Patients with Parkinson's disease were examined
      before and after L-dopa treatment. Transcranial and cervical magnetic stimulation
      were performed and the latency and amplitude of the motor evoked potentials from
      the first dorsal interosseus muscle, the central motor conduction time and the
      duration of cortical inhibition were measured. The motor latency and the silent
      period in patients before treatment were significantly shorter than those of the
      age-matched healthy controls. After six months of L-dopa substitution both motor
      latencies and silent periods increased and approached the normal values. The
      observed changes are thought to be in relation to the mechanisms originating in
      the basal ganglia and acting through inhibitory thalamo-cortical connections at
      cortical level and through rubro- and reticulospinal pathways at the level of
      spinal inhibitory neurons. The transcranial magnetic stimulation is a suitable
      method to assess the efficiency of drugs in patients with Parkinson's disease.

PMID- 10207680
TI  - Reconsiderations about the abnormalities of somatosensory evoked potentials in
      motor neuron disease.
AB  - The frequency of involvement of sensory pathways in motor neuron disease (MND)
      remains the matter of controversy. For this reason the purpose of the present
      work was to test how often sensory system involvement might be detected by
      somatosensory evoked potentials (SEP) studies and then to verify the presence of
      alteration of the sensory conduction and to detect the frequency of abnormalities
      of somatosensory peripheral, spinal, subcortical and cortical potentials in MND.
      SEP were tested after median nerve stimulation at the wrist, recorded from Erb's
      point, Ce2, Ce7 and scalp. Pearson's correlation coefficients test and Wilcoxon
      rank-sum test were used for statistical analysis. 74 patients (22 women and 52
      men) were examined. Mean age of patients was 54.07 +/- 11.24 years; mean duration
      of the disease -19.25 +/- 15.87 months. SEP were abnormal in 39 of 74 patients
      (about 53%) whereas the sensory NCV in median nerve was abnormal in 14 of 74
      patients (19%). The most frequent pattern of abnormalities consisted of the
      absence or delay of cortical responses. The mean values of SEP latencies (N9,
      N11, N13, N20 and P25) were significantly increased in MND patients (p < 0.05) as
      compared with controls. The N9 and N11 latencies correlated with the duration of
      the disease. The results of our study (concerning a large group of MND patients)
      suggest that the involvement of sensory pathways is not rare in MND.

PMID- 10207681
TI  - The association between nerve conduction velocity and the compound action
      potential amplitude during ischemic blocking.
AB  - It is not known in detail how the compound sensory nerve action potential
      amplitude and conduction velocity are associated in nerve ischemia or in other
      conditions like carpal tunnel syndrome. Ischemia was produced by inflating a
      tourniquet around the upper arm in five healthy subjects. When median sensory
      nerve conduction velocities and action potential amplitudes were recorded from
      the third digit, they decreased in parallel, thereby resembling the blocking
      process during wrist flexion in healthy subjects. The area under the action
      potential decreased earlier with longer distances during the ischemic blocking
      process. A theoretical model is presented in which the area under the compound
      nerve action potential is determined by the probability for the single fibre
      action potential to propagate through the internodal distance. This in turn is
      associated with the internodal conduction time.

PMID- 10207682
TI  - Mean power frequency and amplitude of the mechanomyographic signal during maximal
      eccentric isokinetic muscle actions.
AB  - The purpose of the present investigation was to examine the effects of knee
      angular velocity on the mean power frequency (MPF) and amplitude of the
      mechanomyographic (MMG) signal during maximal eccentric (ECC) isokinetic muscle
      actions. Eleven adult subjects performed maximal ECC muscle actions of the leg
      extensors on a calibrated Cybex 6000 dynamometer at knee angular velocities of
      60, 120, and 180 degrees.s-1. MMG was detected by a piezoelectric crystal contact
      sensor placed over the vastus lateralis muscle. There were no significant (p >
      0.05) velocity-related changes in ECC peak torque (PT) or MMG MPF, however, the
      mean MMG amplitude value at 60 degrees.s-1 was significantly less (p < 0.05) than
      that at 180 degrees.s-1. These results did not support our previous hypothesis
      that the velocity-related increase in MMG amplitude for maximal ECC isokinetic
      muscle actions was due to selective recruitment of fast twitch fibers and
      derecruitment of slow twitch fibers with increasing velocity.

PMID- 10207683
TI  - Pathogenesis of pituitary tumors.
AB  - This article focuses on the molecular events associated with pituitary
      tumorigenesis. An accurate description of the molecular pathogenesis of pituitary
      adenomas will have an important impact on clinical practice: identification of
      specific molecular markers of tumor invasiveness and recurrence will allow
      earlier therapeutic intervention and selection of appropriate follow-up
      protocols; family screening may become practically feasible; and potent
      subcellular therapies may be developed for patients with nonfunctioning tumors,
      in whom nonsurgical therapies are ineffective, and for those with resistant
      hormone-secreting tumors.

PMID- 10207684
TI  - The pathology of pituitary tumors.
AB  - The pathologist plays an important role in the distinction of pituitary adenomas
      from other tumors and tumor-like lesions of the sellar region, and in the
      accurate morphologic characterization of pitutiary adenomas. A clinicopathologic
      classification of pituitary adenomas is based on cell differentiation correlated
      with clinical evidence of hormone secretion; this classification emphasizes
      clinically relevant features that can offer guidance for patient management. The
      application of a rational approach to the immunohistochemical analysis of these
      lesions can be used to evaluate pathogenetic and prognostic markers and to
      predict responses to specific therapeutic modalities.

PMID- 10207685
TI  - Current approaches to imaging of the sellar region and pituitary.
AB  - Recent advances in MR imaging have enabled the radiologist to view the pituitary
      gland in its normal and diseased states to a greater extent than ever before. The
      techniques for obtaining quality images of the sellar region and the normal
      appearance of the pituitary gland are discussed. This article also discusses the
      imaging of several pituitary disease processes, with emphasis on pitutiary
      adenomas and recent advances in diagnosis and follow-up. Current controversies
      also are addressed.

PMID- 10207686
TI  - Differential diagnosis of sellar masses.
AB  - The differential diagnosis of nonpituitary sellar masses is broad;
      differentiating among potential etiologies may not always be straightforward
      because many of these lesions, tumorous and nontumorous, may mimic the clinical,
      endocrinologic, and radiologic presentations of pituitary adenomas. This article
      provides an overview of the clinical and radiographic characteristics of both
      pituitary tumors and the nonpituitary lesions found in the sellar/parasellar
      region and discusses, in detail, the specific nonpituitary origins of the sellar
      masses.

PMID- 10207687
TI  - Pituitary surgery.
AB  - Surgical management of pituitary adenomas continues to be a safe and effective
      method for treating many patients with these lesions. The goal of overall
      management should be to provide the patient with the most effective means of long
      term control of this benign but potentially disabling disease. Currently, surgery
      has a significant role. It is hoped that with advances in the understanding of
      pituitary pathophysiology and with advances in pharmacotherapy, surgical
      management may become even more focused, more precise, and more effective over
      time.

PMID- 10207688
TI  - Role of gamma knife therapy in the management of pituitary tumors.
AB  - 1. Gamma knife therapy is an effective method of delivering radiation to
      pituitary tumors that have failed surgery and may be used as primary treatment in
      circumstances in which the patient refuses or is unsuitable for a transsphenoidal
      procedure. 2. Stereotactic radiosurgery with the gamma knife unit is generally
      administered in a single session unlike fractionated radiotherapy, which is
      administered four to five times per week over a 6-week period. 3. Preliminary
      data suggest that resolution of pituitary hypersecretion is faster with gamma
      knife therapy than with conventional radiotherapy. 4. Because of the nature of
      the gamma knife therapy and the fact that the radiation dose conforms to the
      tumor shape, there is a steep fall-off of radiation to surrounding tissue.
      Accordingly, the radiation dose to extrapituitary brain is substantially less
      with gamma knife radiosurgery than with conventional radiotherapy. This suggests
      that the development of second brain tumors and neurocognitive complications,
      which are significant risks with conventional radiotherapy, is much less likely
      with gamma knife surgery. 5. Gamma knife radiosurgery can be used to ablate
      tumors invading the cavernous sinus. 6. Gamma knife radiosurgery is safe as long
      as the dose of radiation to the optic structures is kept under 10 Gy. 7. Long
      term follow-up is required for pituitary tumors treated by gamma knife therapy so
      as to determine its efficacy as well as its effects on pituitary function and any
      resultant complications.

PMID- 10207689
TI  - Medical treatment of prolactinomas.
AB  - Prolactinomas are a common cause of reproductive and sexual dysfunction. Once
      other causes of hyperprolactinemia have been excluded with a careful history,
      physical examination, routine chemistries, and a TSH, MR imaging or computerized
      tomography will delineate the size and extent of the tumor. Medical therapy is
      the initial treatment of choice. When infertility is the primary indication for
      treatment, bromocriptine use has an extensive safety experience and is preferred.
      For other indications, however, cabergoline appears to be more efficacious and
      better tolerated. Transsphenoidal surgery remains an option, especially for
      patients with microadenomas, when medical therapy is ineffective.

PMID- 10207690
TI  - Medical therapy for acromegaly.
AB  - Both somatostatin analogues, which bind to the somatostatin receptor subtypes 2
      and 5, and dopamine agonists, which are specific for the D2 receptor, have been
      used to treat acromegaly. Each of these classes of drugs contains several
      compounds that vary in duration of action, efficacy, and side effect profile.
      Although somatostatin analogues reduce GH levels and alleviate symptoms in most
      patients and restore IGF-1 levels to normal in 60% to 65% of patients, tumor
      shrinkage is limited to 40% of patients. evidence in the literature supports the
      use of these medications as secondary therapy in patients with acromegaly who
      have had surgery and who continue to have elevated GH levels (above 2 ng/mL
      during an oral glucose tolerance test) with or without IGF-1 concentrations that
      are above the upper limit of normal for age. In addition, medical therapy
      indicated in patients who refuse surgery and in patients who are poor surgical
      candidates. The controversial question is whether medical therapy should be an
      option for primary treatment of the acromegalic patient. Currently, ther are no
      data from prospective randomized trials comparing the effects of surgery versus
      somatostatin analogues as first-line therapy for for newly diagnosed acromegalic
      patients. Limited data from nonrandomized studies demonstrate that somatostatin
      analogues are effective long-term in suppressing GH and reducing IGF-1 into the
      normal range in approximately two-thirds of patients who have never undergone
      previous treatment. It is still the consensus that patients with GH-secreting
      microadenomas should undergo surgical resection, because the likelihood of
      complete cure by an experience neurosurgeon is high, at least 70% or greater.
      Successful surgical treatment has the advantage of completely removing the tumor
      in contrast to medical therapy, which rarely produces shrinkage greater than 50%
      despite the fact that IGF-1 and GH levels may be normal. In patients with
      macroadenomas of a size and location that suggest that the chance of complete
      resection is 40% or less, primary treatment with a somatostatin analogue should
      be considered as one option in the initial management of the patient. Another
      option in such an individual would be surgical debulking followed by medical
      therapy, because it is theoretically possible that biochemical cure with medical
      therapy after surgical debulking might be achieved with lower doses. The cost
      effectiveness of these approaches has not yet been determined. Once the decision
      has been made to begin medical therapy, a choice must be made between dopamine
      agonists and somatostatin analogues. Most evidence suggests that somatostatin
      analogues are more effective than dopamine agonists and therefore would be the
      therapy of choice. In select patients, dopamine agonists, particularly the long
      acting agonist cabergoline, may be preferred initially if the patient is
      unwilling to take injections or if the GH elevations are relatively modest (< 10
      ng/mL). Biochemical cure should be assessed by measurement of GH (which can be
      performed 2 hours after an octreotide injection) and IGF-1 concentrations. The
      goal of treatment include reduction of of GH below 2 ng/mL and reduction of IGF-1
      into the normal range. In patients who do not reach these goals, the dose or
      frequency of injection of the somatostatin analogue or both should be increased.
      If such measures are unsuccessful, a dopamine agonist may be added to the medical
      regimen because some studies suggest that combination therapy may be more
      effective in select cases than octreotide therapy alone. If such measures are
      still unsuccessful, other options should be considered, including surgery,
      pituitary radiation, and medical treatment with investigational drugs.

PMID- 10207691
TI  - Newer diagnostic techniques and problems in Cushing's disease.
AB  - The best diagnostic approach to patients with suspected Cushing's disease
      continues to evolve. The introduction of transsphenoidal pituitary surgery as the
      treatment of choice for Cushing's disease as well as the absence of any pituitary
      imaging abnormalities in many patients with Cushing's disease has made accurate
      diagnosis and differential diagnosis essential. In the authors' opinion, two or
      three late night (11 PM) salivary cortisol determinations and the measurement of
      24-hour UFC are the best and simplest means to evaluate patients with suspected
      hypercortisolism. L-DST can no longer be recommended to exclude the diagnosis of
      Cushing's disease, particularly if the hypercortisolism is mild. The combination
      of L-DST and CRH stimulation is a new and apparently sensitive means to establish
      the presence or absence of pathologic hypercortisolism in equivocal cases. In the
      absence of an overt pituitary tumor on MR imaging, inferior petrosal sinus
      sampling with CRH stimulation should be performed to secure the diagnosis of
      Cushing's disease as well as identify the probable location of the corticotroph
      adenoma.

PMID- 10207692
TI  - Medical therapy for Cushing's disease.
AB  - Various drugs have been employed in the management of pituitary-dependent
      Cushing's disease. The neuromodulatory compounds used thus far have demonstrated
      true clinical efficacy only occasionally when employed as sole treatment. Steroid
      synthesis inhibitors are effective in the majority of cases in a dose-dependent
      manner. By their ability to correct hypercortisolism and its severe complications
      quickly, they are suitable for critical cases and in preparation for surgery. The
      clinical experience with the only glucocorticoid receptor antagonist that can be
      administered to humans is still too limited to assess its therapeutic validity.
      No medical strategy can be standardized for this complex condition. Different
      therapeutic tools should be selected according to the form of disease to be
      treated (hypothalamic/pituitary) and the peculiar clinical situation of each
      patient. Combined treatments may achieve better therapeutic efficacy.

PMID- 10207693
TI  - Medical therapy for gonadotroph and thyrotroph tumors.
AB  - Gonadotroph adenomas, a common type of pituitary tumor, are not associated with
      syndromes of hormonal hypersecretion and thus present as pituitary macroadenomas
      with mass effects, or as incidentally discovered pituitary masses. When
      indicated, primary therapy is neurosurgery, but there may be a limited role for
      medical therapy in patients with residual disease. Thyrotroph adenomas are rare
      neoplasms that present with hyperthyroidism and local mass effects. Medical
      therapy may be effective in controlling tumor growth and in achieving
      euthyroidism, when surgery or radiation, or both, do not control the tumor.

PMID- 10207694
TI  - Training in pediatric surgery in Europe.

PMID- 10207695
TI  - Post-pneumonic thoracic empyema in children: a continued surgical challenge.
AB  - The optimal treatment of post-pneumonic thoracic empyema in children is
      controversial. In this retrospective study, we review our seven-year experience
      with open surgical drainage in this condition. Between July 1, 1989, and June 30,
      1996, 20 children (median age 2.7 years, range 1-8 years) underwent thoracotomy
      for post-pneumonic empyema in our department. The diagnosis of thoracic empyema
      was established by the combination of exudate in a pleural tap and the
      demonstration of multi-loculated pleural effusion by either chest ultrasound or
      computerized tomography of the chest. The surgical approach was through a
      posterolateral mini-thoracotomy under general anesthesia. Intrapleural debris,
      gelatinous, and fibrinous material were evacuated and drains were placed, under
      vision, at the most dependent pleural locations. The mean length of pre-hospital
      illness was 5 days (S.D. 3.1 days) and the mean hospital length of stay in a
      pediatric ward prior to surgery, during which all children received intravenous
      antibiotics, was 9.4 days (S.D. 7.7 days). A causative pathogen was identified in
      8 cases: Streptococcus pneumoniae in 6 cases, Streptococcus group A, and H.
      influenzae each in one case. Cultures from the pus removed during surgery were
      sterile for all 19 children who received antibiotics for more than 24 hours prior
      to surgery. Within 48 hours after surgery, fever dropped to < 37.5 degrees C in
      85% of the cases. The postoperative course was uneventful in all cases and the
      children were discharged home 9 days (S.D. 2.8 days) after surgery. We conclude
      that open mini-thoracotomy and removal of the entire empyema sac is a safe and
      curative procedure for children with thoracic empyema.

PMID- 10207696
TI  - Cost analysis of laparoscopic cholecystectomy in children.
AB  - A detailed analysis of the hospital-related costs of laparoscopic cholecystectomy
      in children was performed. Data on 10 laparoscopic cholecystectomies were
      collected prospectively. Pre-, intra- and postoperative variables were assessed
      by standardized questionnaires. The hotel costs and costs for nursing,
      physicians, medicaments and equipment were calculated in detail. Reusable
      instruments were assumed to be used for 50 operations per year over 5 years and
      the costs for disposable instruments were calculated for comparison. In addition,
      the data of 10 children who underwent open cholecystectomy were analyzed
      retrospectively. The mean hospital costs for one laparoscopic cholecystectomy was
      3685 DM. The costs for the operation itself represented 36.5% of the hospital
      costs and were mainly due to expenses for surgeons and nurses. The costs for
      laparoscopic equipment and instruments represented only 8.5% of the total costs.
      If an open procedure instead of a laparoscopic operation had been performed with
      a similar duration of hospital stay, the hospital costs would have been reduced
      by 425 DM (11.5%). In laparoscopic cholecystectomy the costs for medical
      treatment in addition to the operation were 32.8% of the total costs and were
      mainly due to expenses for nursing and physicians, which added up to 165 DM per
      day. The hotel costs represented 30.7% of the total costs and added another 189
      DM per day. Therefore, potential savings in the operation theatre are limited and
      most effective savings may be achieved by shortening the hospital stay. The use
      of disposable instruments would have increased the costs by 844 DM and already 20
      operations per year would have been cheaper performed with reusable compared to
      disposable instruments. Reusable instruments are recommended. Additional 60
      minutes operating time cost 312 DM (5.20 DM/minute) and therefore, laparoscopic
      training courses for surgeons may be cost-effective in order to reduce the costs
      for training in the operation theatre.

PMID- 10207697
TI  - Anatomy of the porta hepatis (PH) as rational basis for the hepatoporto
      enterostomy (HPE).
AB  - PURPOSE: In a prospective study it was investigated whether and to what degree
      the morphology of the porta hepatis has a bearing on the early prognosis of
      children with EHBA. The results will point to consequences of surgery and to the
      formulation of a rational understanding of the successes and failures of HPE.
      METHODS: The macroscopy and the microscopy of the liver was studied on native
      specimen and corrosion preparations of deceased adults, children and embryos. The
      area potentially draining the bile was determined in excised PH specimen of
      children with EHBA. The histologically and planimetrically measured areas were
      correlated to clinical follow-up studies. In order to be able to study
      exclusively the influence of the PH morphology, the conditions of the
      intrahepatical structural changes (level of fibrosis, metric and morphic changes
      of biliary ductules in the Glisson's triads) had to be equal. Under these
      conditions 61 excised PH specimen were evaluated. The level of fibrosis was
      determined according to the definition of Schweizer/Muller 1984 (9). RESULTS: 1)
      Biliary ductules of the PH end in three definable zones according to a regular
      pattern. 2) Biliary ductules of the PH run in a narrow and immediate relation to
      the vascular structures. 3) Biliary ductules of the PH are often hidden between
      the vascular structures of the PH and are not always accessible to preparatory
      exposure for the anastomosis. 4) The quantity of the bile flow is a significant
      function of the total area of the biliary ductules secured in the excised PH
      specimen. 5) Incised biliary ductules at the excision edge may be obstructed
      again in the scarring of the anastomosis, leading to an early interruption of
      bile flow. 6) The opening-up of the biliary ductules in the central zone alone is
      not enough to guarantee a permanent bile flow. Only if intact biliary ductules of
      the two lateral hepatical lobes are secured, can a positive prognosis be made.

PMID- 10207698
TI  - The influence of cholangitis on the prognosis of extrahepatic biliary atresia.
AB  - The prognosis of extrahepatic biliary atresia (EHBA) depends first on the
      progression of the basically existing disease and second on the development of
      preoperative existing alterations of hepatic structure. In addition there are
      postoperative complications which have essential influence on the prognosis of
      the disease. In this context ascending cholangitis poses a very important problem
      for children who have undergone a portoenterostomy. Both the organism and the
      frequency of cholangitis may play a part. This study should outline the influence
      of cholangitis on the prognosis. Since 1972, 146 cases of extrahepatic biliary
      atresia have been treated and followed up postoperatively. Children with a liver
      fibrosis degree IV at surgery will develop a cirrhosis in 86% of cases without
      additional influence of cholangitis. Children with a liver fibrosis degree II/III
      will develop a cirrhosis in 20% of cases without the influence of cholangitis
      after 15 years. But children with a fibrosis degree II/III with one or several
      episodes of cholangitis will develop a liver cirrhosis in 50% of cases after 12.5
      years. The difference is statistically significant. In addition the frequency of
      cholangitis is also an important factor: The more episodes of cholangitis the
      greater the probability of cirrhosis.

PMID- 10207699
TI  - Conservative intestinal surgery to avoid short-bowel syndrome in multiple
      intestinal atresias and necrotizing enterocolitis: 6 cases treated by multiple
      anastomoses and Santulli-type enterostomy.
AB  - Neonates with multiple sites of intestinal atresia (MIA) may be predisposed to
      short-gut syndrome. Anastomoses of the intervening segments may prevent this
      complication. 5 neonates with MIA, one of them with a gastroschisis, were
      operated on: a proximal enterostomy was constructed, a side-to-end anastomosis as
      described by Santulli and several end-to-end anastomoses between the intervening
      intestinal segments (n = 3 to 7) were performed. An additional infant, initially
      operated on for a necrotizing enterocolitis (NEC) was managed with the same
      surgical procedure. Without use of this technique, the remaining length of small
      intestine would have been 28, 27, 40, 58, 70 and 7 cm. This technique enabled an
      intestinal length of 49, 54, 96, 107, 92 and 93 cm respectively to be achieved.
      Ileocecal valve was present in all 5 cases with MIA, but resected in the case
      with NEC. The enterostomy was reversed 7 weeks later. The initial outcome (delay
      of enteral feeding, duration of parenteral nutrition) was good: the babies were
      weaned from parenteral nutrition (PN) after a mean time of 90 days (48 to 163
      days). The prognosis (mean follow-up: 31 months, range 14 to 57) was good with
      regards to growth and development and length of time required before adaptation
      to normal enteral feedings and stools. This surgical method allows complete
      decompression of the proximal jejunum so that nutriment can pass into the distal
      bowel allowing it to enlarge. In cases of MIA, a long tapering proximal
      enteroplasty is a better procedure than resecting more than 5-10 cm of the
      proximal distended and hypertrophied bowel. We prefer to perform an enterostomy
      in association with multiple anastomoses between intervening intestinal segments.
      The enterostomy is preserved for long enough waiting period to enable the
      reversion of the histochemical and morphological changes that may have taken
      place in the bowel.

PMID- 10207700
TI  - Bladder augmentation: urodynamic findings and clinical outcome in different
      augmentation techniques.
AB  - OBJECTIVE: To compare the urodynamic findings and clinical outcome in different
      bladder augmentation techniques. PATIENTS AND METHODS: From 1987 to 1996, 32
      bladder augmentations were performed in 30 (M:F/18:12) patients. Mean age was 8.1
      years (range: 1-15 years) and the mean follow-up period was 3.2 years (range: 6
      months to 8 years). The following techniques were used for bladder augmentation:
      sigmoid colon in eleven cases, stomach in nine cases, ileum in six cases,
      ileocaecum in two cases and rectus abdominis muscle flap (RAMF) in four cases.
      Seven patients also underwent Mitrofanoff procedure to create a continent stoma.
      RESULTS: According to the urodynamic evaluation the mean capacity was 237 +/- 120
      ml in the colonic group, 115 +/- 86 ml in the gastric group, 240 +/- 45 ml in the
      ileal group, 250 +/- 0 ml in the ileocaecal group and 30 +/- 10 ml in the RAMF
      group. The mean compliance was 20.6 +/- 14 ml/cm H2O in the colonic group, 10.7
      +/- 10.4 ml/cm H2O in the gastric group, 21.6 +/- 9 ml/cm H2O in the ileal group,
      25.5 +/- 5.5 ml/cm H2O in the ileocaecal group, 5.8 +/- 1.5 ml/cm H2O in the RAMF
      group. The upper urinary tract was normal without hydronephrosis in all but
      except two patients. These two patients are still treated medically for chronic
      renal failure by the pediatric nephrology team. The patients are using their
      Mitrofanoff or native urethra with clean intermittent catheterization (CIC) or
      self-CIC technique for continence. CONCLUSION: Comparing these five different
      techniques, ileal, ileocaecal and colonic groups were in advantage to achieve
      high volume reservoirs, followed by the gastric group. Regarding complications;
      in colonic cases, mucus problems, stone formation and surgical complications
      related to gastrointestinal tract (intestinal obstruction, perforation) were the
      most common ones. Perineal dermatitis was the main complication in gastric cases.
      In the ileal group, complication rate was low. Absence of mucus production and
      the low postoperative complication rates were the two major advantages of RAMF
      technique. However this technique is not recommended as an augmentation procedure
      due to its low capacity and compliance rates. Recently, ileal augmentation has
      became the most popular method in our institution.

PMID- 10207701
TI  - Our experience in the treatment of the vesico-ureteral reflux with Lich-Gregoir
      antireflux surgical procedure.
AB  - In the period between January 1980 and December 1990 we had applied the operative
      Lich-Gregoir antireflux method on 166 patients, all of whom were children and
      adolescents, and performed 275 antireflux surgical procedures. The application of
      the above mentioned method on our patients yielded a success of 97.8%. There have
      been no intraoperative complications which would affect the ultimate successful
      result of this antireflux operative method. However, early postoperative
      complications occurred in two of our patients, causing infection of the wound,
      which resulted in further ureter stenoses. Recurrent reflux occurred in 4 (2.2%)
      and the stenoses also in other 4 (2.2%) operated ureters. The follow-up lasted
      from 4 up to 14 years. We added our personal detail to the original Lich-Gregoir
      antireflux method considering it to be a further improvement in achieving better
      results. We fixed the ureter to the detrusor with additional stitches in the
      newly formed hiatus, i.e. at the exit of the ureter out of the new submucous
      canal. The possibility of arousing postoperative paraostial diverticula is thus
      avoided, enabling us, at the same time, to enhance the newly formed ureteral
      hiatus in the detrusor. In this way the possibility of postoperative ureter
      stenoses is reduced. According to our experience the above mentioned antireflux
      method does not give good postoperative results in patients with greatly dilated
      and aperistaltic ureter (megacystis-megaureter type), while all other examples
      show a high percentage of postoperative success.

PMID- 10207702
TI  - Could testicular descent in humans be promoted by direct androgen stimulation of
      the gubernaculum testis?
AB  - Gubernaculum testis and androgens play an important role in physiologic
      testicular descent. A direct androgen stimulation of the gubernaculum is only
      possible in the presence of specific receptors, which have not yet been
      demonstrated. We have determined the androgen-binding capacity in 61 samples of
      gubernaculum testis from 48 patients, 34 samples belonging to patients with
      maldescended testes. In 43 out of 61 instances we found androgen binding with
      values up to 72 fmol/mg, with a mean of 13.08 fmol/mg. In 27 samples from
      patients with a deep scrotal positioned gonad the mean androgen-binding capacity
      was 18.74 fmol/mg. In 10 samples from patients with a gonad in the proximal
      scrotum and 19 patients with epifascial ectopy or a low inguinal position the
      mean androgen-binding capacities decreased progressively to 9 fmol/mg and 5.95
      fmol/mg. In the 5 samples from patients with high inguinal or abdominal testes
      the binding capacity of 17.8 fmol/mg did not significantly differ from the value
      obtained in the samples of the normal-positioned gonads, suggesting that
      transabdominal descent is probably not androgen-dependent. We divided the probes
      into receptor status positive for a binding capacity higher than or equal to 10
      fmol/mg, and receptor status negative for a binding capacity under 10 fmol/mg.
      63% of the samples from patients with scrotal positioned testes were receptor
      status positive, 85% of the samples belonging to patients with maldescended
      testes were receptor status negative. Receptor status was negative in patients
      with high scrotal, epifascial or low inguinal and high inguinal or abdominal
      testes in 90%, 95% and 40% of the samples respectively. Immunohistochemical
      examination of 10 samples showed small cell groups with stained nuclei in 2 out
      of 5 patients with normal-positioned testes. All other samples were negative.
      These findings prove that hormone binding was accomplished by specific
      intranuclear receptors. These findings allow for the first time the hypothesis of
      a direct androgen stimulation of the human gubernaculum testis. The probable
      mechanism is an increase in mucopolysaccharides leading to a swelling of the
      gubernaculum, dilating the inguinal canal and promoting testicular descent.
      Although certainly a multifactorial process, quality and quantity of androgen
      receptors would influence the extent of transinguinal testicular descent.

PMID- 10207704
TI  - Anterior jugular venous aneurysm.
AB  - An anterior jugular venous aneurysm in a 4-year-old boy is described. Noninvasive
      radiology confirmed the diagnosis and excluded any deeper cervical venous
      malformation. Surgical excision was uncomplicated. Whilst the internal jugular
      vein is the commonest site of a venous aneurysm, recognition that the anterior
      jugular vein can be affected in isolation may help to avoid diagnostic confusion.
      A unifying concept of pathogenesis is suggested.

PMID- 10207703
TI  - The effect of ATP-MgCl2 on lipid peroxidation in ischemic and reperfused rabbit
      kidney.
AB  - Oxygen metabolites formed during reperfusion of ischemic kidneys prevent recovery
      of renal function after short periods of renal ischemia. The administration of
      ATP-MgCl2 is beneficial to the survival of animals after hemorrhagic shock,
      severe burns, septicemia-peritonitis, post-ischemic hepatic failure, bowel
      ischemia, and endotoxic shock. In this study, the effect of ATP-MgCl2 on lipid
      peroxidation and its curative effect were evaluated by measuring the
      decomposition products of lipid peroxidation, detected as thiobarbituric-acid
      reactive substances in homogenized kidney tissues in ischemic and reperfused
      rabbit kidneys. Ischemia was performed by clamping the right renal artery for 60
      minutes followed by 30 minutes of reperfusion. Thirty-six rabbits were classified
      into 6 groups containing 6 rabbits in each. In the first group, no renal ischemia
      reperfusion (I-R) was designed (Sham group), the right kidney was removed 90
      minutes later. In the second group, I-R was established but nothing given. Saline
      0.25 cc/kg was given into the right renal artery in group 3 two minutes before
      ischemia, and in group 4 two minutes before reperfusion. ATP-MgCl2 17.5 mumol/kg
      (0.25 cc/kg) was given two minutes before ischemia in group 5, and before
      reperfusion in group 6. The right kidneys of the rabbits were removed and
      thiobarbituric-acid reactive substances in the homogenates were measured. In
      addition, histopathological evaluation was performed. High lipid peroxidation
      products were recorded in groups 2-5, whereas in group 6, these levels were low
      similar to those obtained in Sham group (76.72 +/- 1.01 nmol/g tissue). On
      histopathological evaluation, a considerable cell damage resulting from I-R
      trauma especially in proximal tubules was observed. In groups which were under
      saline effect, no histopathological damage was found. Histophatological
      preservation was better in group 6 rather than in group 5. The results of this
      study indicate that ATP-MgCl2 is remarkably effective for preventing the lipid
      peroxidation if given before reperfusion but not before ischemia in experimental
      I-R injury in rabbit kidneys.

PMID- 10207705
TI  - Segmental bronchial atresia--a case report and a literature review.
AB  - Bronchial atresia is a short and juxtahilar bronchus interruption. This uncommon
      malformation leads to an obstructive and systematized emphysema, often associated
      with mucoid impaction. The authors report the case of a 5-year-old boy and review
      the literature in order to recall the radiologic features of this affection,
      which are characterized by an obstructive segmental or lobar emphysema often
      located in the upper lobe. The modern imaging means are not necessary for
      diagnosis. Bronchography confirms the atresia. Neonatal bronchial atresia appears
      as an opaque segment or lobe with retention of the alveolar liquid.

PMID- 10207707
TI  - Dilemmas and challenges of the new millennium.

PMID- 10207706
TI  - Management of prenatally diagnosed congenital cystic adenomatoid malformation of
      the lung.
AB  - We have treated four prenatally diagnosed cases of extensive congenital cystic
      adenomatoid malformation (CCAM) of the lung. The first case in 1982 was
      associated with severe fetal hydrops. After thoracentesis at 31 weeks of
      gestation abruptio placentae occurred, and a female baby was delivered by
      cesarean section. She underwent a right lower lobectomy, but soon died. The
      second baby without hydrops, diagnosed as having CCAM at 26 weeks of gestation,
      was followed conservatively until full term. After birth, it was necessary to
      treat the baby boy with extracorporeal membrane oxygenation (ECMO), but he
      survived. The third baby with fetal hydrops had an indwelling drainage catheter
      inserted into the CCAM at 27 weeks of gestation. The hydrops subsided and the
      baby was delivered at 37 weeks of gestation. He was allowed to breathe
      spontaneously, but was intubated 16 hours after birth. A right lower lobectomy
      was successfully performed 24 hours after delivery. The fourth baby without fetal
      hydrops was followed conservatively until delivery. He underwent left lower
      lobectomy successfully on the 4th day of life. Although management of prenatally
      diagnosed CCAM varies among patients, insertion of an indwelling catheter into
      the cyst appears to be the treatment of choice if indicated; the catheter can be
      maintained for as long as 10 weeks, as shown in Case 3. Cases of CCAM without
      fetal hydrops should also be treated carefully, because persistent fetal
      circulation may occur postnatally.

PMID- 10207708
TI  - Transforming negative parent-adolescent interactions: from impasse to dialogue.
AB  - This treatment development, process research study focuses on resolving in
      session, parent-adolescent conflicts characterized by negative exchanges,
      emotional disengagement, and poor problem solving. These processes have been
      empirically linked to poor developmental outcomes, and clinically linked to poor
      therapeutic progress. Specifically, we examined how a shift of therapeutic focus
      from behavior management to interpersonal relationship failures could resolve
      this impasse and resuscitate therapeutic momentum. A task analysis approach was
      used to verify the presence of the impasse, to illuminate its core features, and
      to define the therapist and client behaviors associated with resolving it. In
      Part 1 of this two-part series, we presented the final performance map that
      represented that family's cognitive, emotional and behavioral interactions
      necessary to resolve the impasse. This article, Part II, focuses on the
      theoretical foundation of the intervention strategies, the phenomenology of the
      impasse, and the therapist's skills needed to facilitate it.

PMID- 10207709
TI  - Couple-responsible therapy process: positive proximal outcomes.
AB  - Therapist-couple struggle vs. cooperation is linked to clinical outcome. This
      research conceptualizes and investigates treatment process as it relates to the
      occurrence of struggle versus cooperation. Models of couple-responsible and
      therapist-responsible process in couple therapy were developed. Couple
      responsible process consists of enactments, accommodation, and inductive process.
      Therapist-responsible process consists of primary therapist-couple interaction,
      therapist interpretation, and direct instruction. In counterbalanced order, 25
      couples were exposed to couple-responsible and therapist-responsible episodes
      during one therapy session. Couples reviewed videotapes of the episodes and
      completed measures of responsibility, struggle, and cooperation. Perceived
      responsibility was higher and struggle was lower during couple-responsible
      episodes. No difference in cooperation was found. Presence or absence of a
      contrast condition, where couples reported on one therapist process after already
      experiencing its opposite, led to main effects for responsibility and struggle,
      and mediated effects of struggle and cooperation. Generally speaking,
      responsibility was even higher during couple-responsible episodes and even lower
      during therapist-responsible episodes when contrast was present. Similarly,
      struggle was even lower during couple-responsible episodes and even higher during
      therapist-responsible episodes when contrast was present. For both couple
      responsible and therapist-responsible episodes, cooperation was negatively
      affected by a shift from the prior, opposite therapist process. Significant
      proportions of the variance in responsibility, struggle, and cooperation,
      however, were not accounted for by therapist process alone.

PMID- 10207710
TI  - The importance of cultural sensitivity and therapist self-awareness when working
      with mandatory clients.
AB  - Systemic therapy emphasizes the importance of understanding each relationship in
      the context of its ecosystem. Considerations such as the influence of social
      agencies, culture, and the therapist's self-awareness are described in the
      literature as amplifying lenses within the therapeutic relationship. When a
      minority client is caught in the web of larger system agencies and is mandated to
      family therapy, systemic family therapy, which incorporates multiple lenses and
      attends to the context of social background, may provide a better understanding
      of the client's reality. Clinical cases show that therapists may slip into veiled
      racist and discriminatory attitudes with minority clients. Self-awareness, "soul
      searching," and appropriate supervision may be of tremendous help in learning
      from such experiences. A case example illustrates the application of this
      approach.

PMID- 10207711
TI  - The association between spouses' self-reports of attachment styles and
      representations of family dynamics.
AB  - The current research assesses the association between spouses' self-reports of
      attachment style and their perceptions of family dynamics. The sample included 93
      Israeli married couples with young children. Both husbands and wives completed
      the adult attachment style scale and the perceived and ideal versions of FACES
      III. Findings showed that spouses whose self-reports endorsed the secure style
      perceived relatively high levels of family cohesion and adaptability; persons who
      endorsed the anxious-ambivalent style reported high levels of family cohesion but
      low levels of adaptability; and persons who endorsed the avoidant style reported
      relatively low levels of both family dimensions. In addition, significant
      associations were found between reports of attachment styles, on the one hand,
      and ideal representations of family dynamics, the marital partner's
      representations of family dynamics, and spouses' discrepancies in these
      representations, on the other. Findings are discussed in terms of attachment
      theory.

PMID- 10207712
TI  - Depressive symptoms among spousal caregivers of institutionalized mates with
      Alzheimer's: boundary ambiguity and mastery as predictors.
AB  - The goal of this study was to identify factors that predict whether or not
      community-dwelling spouses experience depressive symptoms upon
      institutionalization of a mate with Alzheimer's disease. Eighty-four community
      dwelling spouses (50 wives/34 husbands) completed questionnaires. Boundary
      ambiguity alone accounted for 51% of the variability in the depressive symptoms
      score, while mastery alone was found to account for 32%. The total explained
      variance, when controlling for demographic variables, was 68%. In the stepwise
      regression analysis, it was observed that mastery did not add significantly to
      the explanation of the depressive symptom score over and above boundary
      ambiguity. However, boundary ambiguity and mastery were somehow linked together
      and were powerful in explaining caregiver symptoms of depression. If a goal is to
      keep caregivers healthy, then interventions and education about how to live with
      ambiguity and how to be masterful in spite of the ambiguous status of one's mate
      seem necessary. Clinical implications are discussed. Future research might build
      upon this study's limitations for an even better understanding of factors that
      relate to caregiver depressive symptoms.

PMID- 10207713
TI  - Marital interaction in dyadic and triadic contexts: continuities and
      discontinuities.
AB  - While the systemic metaphor used in much current family research requires
      examination of the interrelationships among individuals, relationships, and the
      family as a whole, work on triadic relationships has generally been missing. This
      research examined the presence of second-order effects in marital interaction:
      changes in interactions between spouses when the husband-wife dyad became a
      parent-parent-child triad. Results indicated the presence of consistent context
      effects. Parental behavior when alone was not a good predictor of parental
      behavior in the presence of a child: behaviors occurred at significantly lower
      levels in parental dyads than in parent-parent-child triads, and correlations
      across the two contexts were less than consistent. Results are discussed in light
      of their implications for observations of families.

PMID- 10207714
TI  - Sibling accounts of attention deficit hyperactivity disorder (ADHD).
AB  - The goal of this research was to generate a description of how siblings in
      families with attention deficit hyperactivity disorder (ADHD) children
      experienced and lived with this chronic behavioral disorder. Interview and diary
      data from 11 families (N = 43) were analyzed using the constant comparative
      method. Data analysis revealed that siblings felt victimized by their ADHD
      sibling and that their experience of victimization was often minimized or
      overlooked in the family. Findings suggest that there is a need for increased
      social and mental health services for all members of the family over the course
      of the disorder, and that the effects on siblings, in particular, can be
      potentially quite deleterious to their health and well-being.

PMID- 10207715
TI  - Method for constructing confidently ordered linkage maps.
AB  - We describe a method for identifying, from a comprehensive genetic map, the most
      dense framework of confidently ordered markers. The approach uses the number of
      observed recombination events between each pair of markers, and finds the largest
      subset of markers for which adjacent loci are separated by at least one
      recombination. We illustrate the approach using a short region of chromosome 7p.

PMID- 10207716
TI  - Comparison of family history measures used to identify high risk of coronary
      heart disease.
AB  - We examined 15 published continuous family history measures (scores) as well as
      two new formulations in terms of several desirable properties. We applied the
      scores to sample pedigrees and found that some systematically increase with
      family size. In contrast to aggregate scores, non-aggregate scores are sensitive
      to the age, sex, and covariate status of individual relatives but are unstable
      when the families are small. We also applied these scores to our own population
      case-control data, characterised by a high proportion of missing and false
      negative responses. In these small families, all scores provided significant
      discrimination between CHD cases and controls beyond the usual categorical
      definition of positive family history, but appeared no better than detailed
      categorical definitions or even simple counts. Our new formulations offer no
      solution to the problems of few data; most scores apply asymptotic approximations
      to differences between observed and expected number of affected relatives and are
      not suited to small families. All scores would be improved by ruling out families
      with only one affected relative, as is being done in the NHLBI Family Heart
      Study. We recommend that researchers, when using a family history measure,
      consider the number of informative families and other characteristics of their
      data prior to choosing any particular formulation.

PMID- 10207718
TI  - Effects of misclassification on estimates of relative risk in family history
      studies.
AB  - Two types of misclassification that commonly occur in family-genetic studies are
      distinguished: 1) nondifferential misclassification, in which the probability of
      error as to phenotype (presence or absence of psychiatric disorder) does not
      depend on exposure status (being kin to a case or control proband) and 2)
      differential misclassification, in which it does. Nondifferential
      misclassification of phenotype reduces the observed relative risk towards the
      null value, sometimes quite dramatically. Differential misclassification can bias
      the observed relative risk in either direction, depending on the different values
      of sensitivity and specificity among relatives of cases and controls. The impact
      of these biases on genetic-epidemiologic studies is reviewed and discussed. In
      particular, the ability to detect major gene effects from the pattern of relative
      risks in first-, second-, and third-degree relatives can be severely compromised.
      Although there are some methods available to correct the effects of
      nondifferential misclassification, a major priority for family history studies is
      to minimize differential misclassification.

PMID- 10207717
TI  - Recent progress in understanding the genetic susceptibility to osteoporosis.
AB  - Family and twin studies have established a genetic contribution to the etiology
      of osteoporosis. The genes and allelic variants conferring osteoporotic risk are
      largely undefined, but the number of candidates has increased steadily in recent
      years (Table I). Osteoporosis is a complex disease, and allelic variation in many
      other candidate-genes including those that encode growth factors, cytokines,
      calciotropic hormones, and bone matrix proteins are likely to also play a role
      and warrant systematic investigation. Most family and association studies to date
      have focused on the genetic contributions to bone density, a major determinant of
      bone strength and fracture risk. Bone density is not the only determinant of
      skeletal fragility, however, and genetic influences on fracture risk are
      independent of bone density [Cummings et al., 1995]. The microarchitectural
      properties and overall size and geometry of bone also influence skeletal strength
      [Bouxsein et al., 1996], and the genetic influences on these phenotypes should be
      investigated more rigorously. Even fewer studies have assessed the association
      between candidate-gene variation and the risk of fracture, the most important
      clinical outcome of osteoporosis. Large-scale molecular epidemiologic studies
      will be increasingly necessary in the future to quantify the relative, absolute
      and attributable risks of fracture associated with specific genetic variants.
      Osteoporosis is a complex, multifactorial disease, and most candidate-gene
      association studies have had limited statistical power to assess gene-gene and
      gene-environment interaction. Although gender plays an important role in the
      development of osteoporosis, genetic studies have almost exclusively focused on
      women, and have not tested whether gender modifies the association between
      genetic variation and osteoporotic risk. Therefore, future genetic studies will
      need to recruit larger samples of individuals including men. Rapid additional
      progress in our understanding of the molecular basis of osteoporosis can be
      expected in the near future as ongoing genome-wide linkage [Spotila et al., 1996]
      and candidate-gene association analyses are completed. Linkage analyses in
      families at high-risk for rare metabolic bone diseases should also yield
      important clues to the pathogenesis of osteoporosis. Recent examples are the
      mapping of loci for both high [Johnson et al., 1997] and low [Gong et al., 1996]
      bone mass to chromosome 11q and osteopetrosis to chromosome 1p [Van Hul et al.,
      1997]. Similar ongoing studies in baboons [Rogers and Hixson, 1997] and mice
      [Beamer et al., 1997] may reveal additional loci whose human homologs contribute
      to osteoporotic risk. The improved understanding of osteoporosis that will emerge
      from these genetic studies should lead to better diagnosis of this disease and
      new treatment and prevention strategies.

PMID- 10207719
TI  - Inheritance of LDL peak particle diameter: results from a segregation analysis in
      Israeli families.
AB  - Genetic and environmental determinants of LDL peak particle diameter (LDL-PPD)
      were investigated in a sample of 80 kindreds residing in kibbutz settlements in
      Israel. The sample included 182 males and 191 females ages 15-93 years. LDL-PPD
      levels were first adjusted for variability in sex and age. Commingling analysis
      demonstrated that a mixture of two normal distributions fit the adjusted LDL-PPD
      levels better than did a single normal distribution. Complex segregation analysis
      was first applied to these sex and age adjusted data but was not conclusive.
      However, when the regression model for sex and age allowed coefficients to be
      ousiotype (class) specific, the mixed environmental model was rejected while a
      major Mendelian model was not. These results suggest that the particular
      genotypes determined by the major gene, which are associated with different
      phenotypic variances, are likely to be more realistic, and that this analytic
      approach can contribute to improving our understanding of the genetics of LDL
      particle size.

PMID- 10207720
TI  - Linkage analysis of candidate obesity genes among the Mexican-American population
      of Starr County, Texas.
AB  - Recent advances in the molecular basis of body fat regulation have identified
      several genes in which genetic variation may influence obesity and related
      measures in human populations. Genes that have been shown to have a regulatory
      function in the control of body fat utilization, eating behavior, and/or
      metabolic rate in rodent models of obesity include leptin (LEP), leptin receptor
      (LEPR), neuropeptide Y (NPY), NPY Y1 receptor (NPYY1), glucagon-like peptide-1
      (GLP-1), GLP-1 receptor (GLP1R), and uncoupling protein 1 (UCP1). We have typed
      microsatellite markers located within or near these seven candidate obesity genes
      in 302 non-diabetic individuals from 59 Mexican-American families from Starr
      County, Texas. Sib pair linkage analysis was used to examine linkage between
      these genes and obesity status (obese siblings only; n = 170 pairs) and several
      obesity-related quantitative variables (all siblings; n = 545 total sibling
      pairs). Significant linkage (P = 0.042) was found between obesity and NPY within
      the obese sibling pairs. No other candidate gene was linked to obesity status in
      this subsample. Consistent with the obese sib pair linkage results, NPY showed
      evidence of linkage to body weight (P = 0.020), abdominal circumference (P =
      0.031), hip circumference (P = 0.012), diastolic blood pressure (P = 0.005), and
      a composite measure of body mass and size (P = 0.048) in the entire sibling
      sample. Other significant linkages observed were between LEP and waist/hip ratio
      (P = 0.010), total cholesterol (P = 0.030), and HDL cholesterol (P = 0.026) and
      between LEPR and fasting blood glucose (P = 0.018) and diastolic blood pressure
      (P = 0.003). These results support further investigation of NPY, LEP, and LEPR to
      identify genetic variation that may influence obesity status, glucose and lipid
      metabolism, and blood pressure in Mexican Americans.

PMID- 10207721
TI  - A genealogical study of Alzheimer disease in the Saguenay region of Quebec.
AB  - We performed an analysis of inbreeding and kinship among the ascending
      genealogies of 205 autopsy-confirmed Alzheimer disease (AD) subjects recruited in
      the Saguenay area of Quebec. We hypothesized that if some traits pertaining to
      the disease were determined by inherited factors, and if the corresponding genes
      were not too frequent in the population, it might be possible to detect some
      clusters of patients related to common ancestors and presenting a level of
      kinship and/or inbreeding higher than is observed in the unaffected population of
      the same age. In view of the heterogeneity of the disease, we also verified if
      some of the factors investigated could be associated more specifically with
      subsets of cases based on age of onset and on apolipoprotein E (APOE) genotype.
      Results were compared with those obtained on 205 controls matched for gender,
      place and year of birth. We found that late-onset AD cases with an APOE-epsilon 4
      were significantly more inbred than controls and that this increase was explained
      by the high level of inbreeding of a few cases whose parents were related at the
      first-cousin level. This could possibly indicate the implication of a recessive
      element in a small subset of AD cases in the Saguenay population. We also found
      that late-onset epsilon 4+ cases were significantly more closely related among
      themselves than with controls. This increase in kinship may be attributable to
      the presence of the epsilon 4 allele or to some other unidentified genetic factor
      possibly acting in conjunction with APOE-epsilon 4.

PMID- 10207723
TI  - Etiology of the inflammatory bowel diseases.
AB  - Inflammatory bowel diseases (IBD) are complex disorders. While the exact etiology
      of these diseases remains unknown, recent progress in the epidemiology and
      genetics of IBD has clearly demonstrated both environmental and genetic factors
      to play a role in the development of the disease, and it is expected that some
      risk factors are common for both Crohn's disease (CD) and ulcerative colitis
      (UC). The environmental factor(s) are associated with the Western way of life in
      the second half of the twentieth century. Cigarette smoking is presently the best
      known environmental factor. However, the effect of tobacco is opposite in CD and
      UC. A familial history of IBD is the most important risk factor for developing
      the disease, suggesting a genetic predisposition to IBD. This hypothesis has
      recently been confirmed by the localization of at least two susceptibility loci
      on chromosomes 12 and 16. These genes seem to play a role in both CD and UC. They
      must now to be identified.

PMID- 10207722
TI  - Bivariate genetic analysis of fasting insulin and glucose levels.
AB  - The main aim of this study was to estimate the relative influence of genes and
      environment on fasting insulin levels, which were considered a proxy of insulin
      resistance. Possible sex differences in genetic and environmental influences, and
      the origin of the covariance between fasting insulin and glucose were
      investigated. Subjects were 209 pairs of middle-aged twins, divided into 5 sex-by
      zygosity groups. A general bivariate model and a reciprocal causation model
      including fasting insulin and glucose were used in the analyses. For both
      quantitative genetic models, a model specifying additive genetic and unique
      environmental factors, which were the same in males and females, showed the best
      fit to the data. Heritability estimates were modest and highly similar in both
      models: 20-25% of the variance in fasting insulin, and around 50% of the variance
      in fasting glucose levels could be attributed to genetic factors. The two models
      could not be discriminated on the basis of their fit to the data. A submodel of
      the general bivariate model suggested that the covariance between glucose and
      insulin has a unique environmental basis, whereas for the reciprocal causation
      model both causal paths were needed to explain the phenotypic correlation between
      insulin and glucose and estimates of the reciprocal paths were of opposite sign,
      an indication for the expected negative feedback loop.

PMID- 10207724
TI  - Genetics in gastrointestinal disease: how much can we learn from molecular
      analysis?

PMID- 10207725
TI  - Inflammatory bowel disease and the genes for the natural resistance-associated
      macrophage protein-1 and the interferon-gamma receptor 1.
AB  - The genes for the interferon-gamma receptor 1 and the natural resistance
      associated macrophage protein 1 (NRAMP1) control the immune response to
      intracellular microbial pathogens. Such pathogens, in particular Mycobacterium
      paratuberculosis, have been implicated in the pathogenesis of Crohn's disease. We
      studied markers in the genes for NRAMP1 and two mutations in the interferon-gamma
      receptor in relation to inflammatory bowel disease (IBD) in the following groups:
      270 healthy individuals, 74 patients with Crohn's disease, 72 patients with
      ulcerative colitis, and 40 patients with primary sclerosing cholangitis. We
      studied the allele frequencies of two restriction fragment length polymorphisms
      in the gene for NRAMP1 and the prevalence of two mutations in the interferon
      gamma receptor 1 gene. The markers in the NRAMP1 gene were not associated with
      inflammatory bowel disease. Also, the mutations in the interferon-gamma receptor
      1 were not found in the 186 IBD patients. Genetic markers in NRAMP1 are thus not
      associated with IBD. Therefore this gene is not likely to play a role in the
      pathogenesis of IBD. The mutation in the interferon-gamma receptor was not found
      in our IBD patients group.

PMID- 10207726
TI  - A role for transcription factor NF-kappa B in intestinal inflammation.
AB  - Nuclear factor (NF) kappa B is a transcription factor that controls the
      transcription of a variety of cellular genes regulating the inflammatory
      response. Many proinflammatory cytokines are transcriptionally regulated by NF
      kappa B, and their increased expression has been implicated in the pathogenesis
      of inflammatory bowel disease (IBD). Even though it seemed clear that the
      increase in proinflammatory cytokine production in IBD is crucial for the
      initiation and perpetuation of chronic intestinal inflammation, the elements
      governing this dysregulation of enhanced cytokine production remained unclear.
      This review discusses a series of recent studies that demonstrate the activation
      of NF-kappa B in the inflamed mucosa, and that shed new light on the central
      pathogenic role of NF-kappa B in chronic intestinal inflammation. In addition to
      describing the activation of NF-kappa B, excitement has been generated by reports
      that define the molecular targets of anti-inflammatory agents, and that
      demonstrate the effective blockade of NF-kappa B in intestinal inflammation.
      These new insights into the activation and inhibition of NF-kappa B have opened
      new and promising avenues for a more specific treatment of chronic intestinal
      inflammation.

PMID- 10207727
TI  - Does microcirculation play a role in the pathogenesis of inflammatory bowel
      diseases? Answers from intravital microscopic studies in animal models.
AB  - The potential role of intestinal microcirculation for the development of
      inflammatory bowel diseases (IBD) has not been systematically investigated,
      mainly because of methodological problems. Using a well-established rodent model
      of IBD and intravital microscopy, the present study investigated whether (and
      when) gut microcirculation is disturbed in IBD, and whether microcirculatory
      disorders contribute to histological and functional alterations in the
      development of IBD. Colitis was induced by rectal injection of trinitrobenzene
      sulfonic acid. After 1, 3, and 15 days rats were laparotomized for intravital
      microscopic determination of mucosal colonic blood flow. In a second series it
      was examined whether enhancing colonic capillary blood flow by hemodilution
      therapy stabilizes colonic wall resistance and other electrophysiological
      parameters of gut permeability. Additional measurements involved hemodynamic
      monitoring and histological examinations. Colonic capillary blood flow was
      significantly decreased 3 days after colitis induction (1.8 +/- 0.05 vs. 2.6 +/-
      0.04 nl/min in healthy control animals) when histology revealed signs of acute
      inflammation, and normal values after 15 days (2.4 +/- 0.06 nl/min) when chronic
      histological changes were evident. Hemodilution therapy enhanced colonic
      capillary blood flow in the initial stage (2.1 +/- 0.02 vs. 1.6 +/- 0.02 nl/min
      in saline-treated animals with trinitrobenzene sulfonic acid colitis) and
      improved gut resistance and electronic chloride secretion (73 +/- 15 vs. 33 +/- 8
      microA cm2). Histological alterations were not significantly attenuated. Impaired
      colonic capillary blood flow in the initial stage of experimental colitis and
      improved mucosal microcirculation with stabilized gut permeability suggests that
      the early microcirculatory disturbances precede chronic histological changes and
      influence functional alterations in the course of the disease. Research should be
      continued in this field because important mechanisms in the pathogenesis of IBD
      and potentially therapeutic (vasoactive) substances may otherwise be overlooked.

PMID- 10207728
TI  - IgG, albumin, and sCD44 in whole-gut lavage fluid are useful clinical markers for
      assessing the presence and activity of pouchitis.
AB  - Pouchitis is the most significant long-term complication in patients with
      ileoanal pouch anastomosis (IAP) and is especially frequent in patients with
      ulcerative colitis. There is an urgent need for simple and objective parameters
      to assess the presence and activity of pouchitis. Whole-gut lavage fluid (WGLF)
      was collected from 34 patients [8 with pouchitis (PDAI > or = 7 points) and 26
      without pouchitis (Pouchitis Disease Activity Index, PDAI, < 7)]. Patients with
      active ulcerative colitis (n = 8) served as controls. Concentrations of IgG and
      sCD44 in WGLF were measured by enzyme-linked immunosorbent assays and those of
      albumin by immunoturbidimetry. Similar to the case in active ulcerative colitis,
      concentrations of IgG, albumin, and sCD44 in WGLF were significantly increased in
      acute pouchitis and reached high specificity (IgG 96%, albumin 96%, sCD44 100%)
      and acceptable sensitivity (75%) for the diagnosis of acute pouchitis. These
      parameters were also closely correlated with disease activity as determined by
      PDAI and endoscopic scoring indices. Assay of protein concentrations in WGLF is
      thus a simple and objective means for grading inflammation of the pouch and may
      be useful as a quantitative index of disease activity in clinical studies.

PMID- 10207729
TI  - Transepithelial transport processes at the intestinal mucosa in inflammatory
      bowel disease.
AB  - Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases
      (IBD) of unknown etiology. Oral absorption studies have shown an increased
      intestinal permeability for various sugar molecules in patients with IBD and
      their healthy relatives as a possible pathogenetic factor. However, the various
      transport pathways through the mucosal barrier have not yet been examined. This
      study therefore investigated whether antigens pass the epithelial barrier by a
      transcellular or a paracellular pathway. Mucosa of freshly resected specimens
      from CD (n = 10) or UC (n = 10) patients was investigated by immunoelectron
      microscopy and compared with healthy mucosa. Epithelial transport was studied
      with the antigens ovalbumin and horseradish peroxidase after defined incubation.
      Labeling density of subunit c of ATP synthetase was determined in mitochondria of
      enterocytes of all specimens. In all specimens epithelial transport of OVA and
      HRP was principally transcellular through enterocytes with normal ultrastructure,
      although some tight junctions in CD and UC were dilated. Antigens were
      transported within vesicles to the basolateral membrane 2.5 min after incubation.
      The level of enterocytes with electron-lucent cytoplasm containing a high amount
      of antigens was higher in CD and UC than in healthy mucosa, depending on the
      grade of inflammation. ATP synthetase was significantly decreased in electron
      lucent cytoplasm of CD and UC to normal ultrastructure of healthy mucosa. Our
      study shows that ovalbumin and horseradish peroxidase taken up by the apical
      membrane reach the paracellular space by vesicular transport in healthy and IBD
      enterocytes within a few minutes. Transcellular pathway is affected in both CD
      and UC, which is indicated by a high level of antigens within the cytosol. We
      speculate that increased intestinal permeability in IBD results substantially
      from enhanced transcellular transport.

PMID- 10207730
TI  - Anti-TNF strategies in Crohn's disease: mechanisms, clinical effects,
      indications.
AB  - Although the cause of Crohn's disease remains obscure, considerable progress has
      been made in recent years in unraveling the pathogenesis of the inflammatory
      processes seen in chronic idiopathic inflammatory bowel diseases. Th-1
      lymphocytes seem to orchestrate the inflammation through the production of
      proinflammatory cytokines such as interferon-gamma, interleukin-1 beta, and tumor
      necrosis factor (TNF) alpha. Since the isolation and characterization of TNF and
      its two receptors detailed regulatory processes for transcription, secretion, and
      postreceptor actions of TNF are now rapidly being discovered. Genetically
      engineered monoclonal antibodies specifically directed against TNF-alpha are only
      the first drugs acting against TNF, available for clinical use now in the
      treatment of Crohn's disease. A single intravenous injection of these mono
      antibodies produce very dramatic clinical, endoscopic, and histological responses
      in most refractory patients. More data on long-term safety, efficacy (mainly
      after repeated infusions) and the exact role in combination with standard
      therapies are awaited. Until then these drugs should be reserved for patients not
      responding to standard immunomodulatory therapy and not amenable to surgery. The
      exciting "TNF story" very nicely illustrates how the benchmark of basic
      immunological research now provides us with very potent and rationally designed
      drugs. Careful monitoring of safety of repeated and long-term use of these
      agents, interfering with very basic physiological events, is mandatory.

PMID- 10207731
TI  - Quality of life in Korean patients with inflammatory bowel diseases: ulcerative
      colitis, Crohn's disease and intestinal Behcet's disease.
AB  - Health-related quality of life (HRQOL) is an important outcome factor in chronic
      diseases such as inflammatory bowel disease (IBD). This study used the Korean
      translation of the disease-specific, self-administered Inflammatory Bowel Disease
      Questionnaire (IBDQ) to compare HRQOL in ulcerative colitis (UC; n = 98), Crohn's
      disease (CD; n = 49), and intestinal Behcet's disease (BD; n = 34). In addition
      to the current status, patients were asked retrospectively to recall their
      symptoms at the beginning and during the worst period of their disease. Disease
      activity was measured by St. Mark's Activity Index, Crohn's disease Activity
      Index (CDAI), and the Harvey-Bradshaw Index (HBI). In all IBD patients, including
      those with BD, the IBDQ total score during the worst period was significantly
      lower than that at present and that at the beginning of the disease. However,
      there were no significant differences between groups regarding the total IBDQ
      score or its various dimensions. In UC a strong correlation between IBDQ scores
      and St. Mark's Activity Index was observed (r = -0.708, P < 0.001). IBDQ scores
      were also highly correlated with CDAI and HBI in both CD (r = -0.506, P < 0.001
      for CDAI; r = -0.600, P < 0.001 for HBI) and BD (r = -0.687, P < 0.001 for CDAI;
      r = -0.531, P < 0.001 for HBI). However, the current IBDQ score was not related
      to demographic parameters such as gender, age, educational status, economic
      status, and marital status as well as disease factors such as duration of
      disease, history of operation or hospital admission, extent of disease in UC,
      involved region in CD, and clinical type in BD. We conclude that the Korean IBDQ
      is a responsive and promising instrument for measuring HRQOL of IBD patients in
      clinical trials. In addition, the IBDQ can be helpful in developing a disease
      specific activity index in BD.

PMID- 10207732
TI  - Therapy of prednisone-refractory collagenous colitis with budesonide.
AB  - Collagenous colitis is a rare cause of chronic watery diarrhea. No effective
      standard treatment has yet been established. Based upon anecdotal reports some
      anti-inflammatory and symptomatic drugs seem to have some therapeutic efficacy.
      Prednisone is widely believed to be the most effective treatment. Here we
      describe three female patients with histologically confirmed collagenous colitis
      refractory to therapy with prednisone. Each had received prednisone with a high
      starting bolus and lower dose maintenance therapy for their disease. However,
      definite clinical remission could not be achieved. After the administration of 3
      x 3 mg/day controlled ileal release (CIR) capsules of budesonide the symptoms
      resolved immediately. The mean follow-up after beginning budesonide was 11 months
      (range 7-18). Two patients are still on budesonide. One had had a quick relapse
      of diarrhea after stopping her treatment. Budesonide therapy was therefore
      resumed. She has remained symptom-free on a lower daily dose of 2 x 3 mg/day
      budesonide. One patient has been in remission for more than 1 year after a 3
      month course of budesonide. Budesonide is a topically acting steroid with rapid
      absorption, high receptor affinity, and low systemic bioavailability, thus
      causing almost no side effects. As yet only few case reports have been published
      on the use of budesonide for collagenous colitis. We present here the first three
      cases of prednisone refractory collagenous colitis successfully treated with
      budesonide.

PMID- 10207733
TI  - Is potent topical steroids the solution in collagenous colitis?

PMID- 10207735
TI  - Colorectal operative experience in general surgical training.
AB  - BACKGROUND: Surgical trainees often feel that their operative training is
      inadequate--trainers usually do not share this view. METHODS: The distribution of
      colorectal operative surgical workloads between consultants and trainees was
      examined over a 15-year period in the Colorectal Service at the Wellington School
      of Medicine. RESULTS: Consultants performed 947 operations and trainees performed
      1012 operations. The average age of patients operated on by trainees was lower
      than that of those operated on by consultants. Trainees performed more emergency
      surgery. Anorectal surgery, except fistula surgery, was more commonly performed
      by trainees, whereas abdominal colorectal surgery was more commonly performed by
      consultants. Trainees had lower postoperative morbidity and mortality rates. The
      diseases predominantly treated by consultants and trainees differed. Twenty-four
      percent of patients with colorectal cancers and 25% of patients with diverticular
      disease were managed operatively by trainees. Yearly trainee workloads for minor
      anorectal conditions were similar to those of trainees in the USA. CONCLUSION:
      Although this small colorectal audit provides some information about trainees'
      operative experience, until all surgical procedures performed by all surgical
      trainees are accurately audited and criteria for adequacy of operative training
      are clearly stated, it will not be possible to say whether our training programs
      provide adequate operative training or not.

PMID- 10207734
TI  - Detection of colonic dysplasia by light-induced fluorescence endoscopy: a pilot
      study.
AB  - Light-induced fluorescence endoscopy (LIFE) has been shown to differentiate
      between normal mucosa and dysplastic lesions, and dysplastic lesions of the colon
      occult to routine white-light colonoscopy may thus be visualized by LIFE. We
      compared the sensitivity and specificity of LIFE to routine white-light
      colonoscopy in patients with colonic dysplasia. In a pilot study 20 patients with
      colonic adenoma, inflammatory bowel disease, or with a history of colon cancer
      were screened for colonic dysplasia during routine colonoscopy. Forty-two sites
      of mucosal abnormalities regarded as suspicious for dysplasia during white-light
      colonoscopy were additionally examined with a prototype LIFE system. Biopsies
      were taken from all 42 colonic sites. The LIFE images were classified as positive
      or negative for dysplasia. Sensitivity and specificity were calculated by
      correlating positive and negative findings to the histopathological results.
      Histopathology detected 21 adenomas with low-grade dysplasia and one with high
      grade dysplasia. All dysplastic lesions were found by routine white-light
      endoscopy. The specificity of conventional white-light endoscopy was 80%. Of the
      22 dysplastic lesions 20 were detected by LIFE (sensitivity 91%). The specificity
      of LIFE was 90% (two false-positive results). LIFE combined with conventional
      endoscopy may thus improve the detection of colonic dysplasia.

PMID- 10207736
TI  - Carcinoembryonic antigen: its value in the follow-up of patients with colorectal
      cancer.
AB  - We examined the value of carcinoembryonic antigen (CEA) monitoring for detecting
      treatable recurrence of colorectal carcinoma. CEA assays were undertaken in 193
      patients over a 2-year period. The levels in 34 patients were raised in one or
      more assays above the laboratory-defined upper limit of normal; 31 cases were
      reviewed retrospectively. In 10% of patients there were Dukes' A lesions at the
      initial resection, in 39% Dukes' B, and in 52% Dukes' C1 or C2. Tumours were
      rectal in 61%. Median follow-up was 3 years (range, 16 years-2 months). In 23 of
      31 (74%) there were symptoms or signs of recurrent disease prior to or
      simultaneously with an observed rise in CEA; in 8 the CEA rise preceded the onset
      of symptoms or the appearance of signs. Of the 31 cases 26 underwent
      investigation for recurrent disease, but in only 6 of these was the investigation
      driven by the observed rise in CEA rather than the onset of symptoms or presence
      of signs. Three of these six were false-positive results (50%), one has been lost
      to follow-up, and two had confirmed recurrence. Neither of the two with
      recurrence had operable disease. One of the two had no further treatment, and one
      underwent laparotomy at which multiple peritoneal seedlings were found. In both
      of the two cases going to laparotomy, one of which was prompted by a high CEA,
      widely disseminated disease was found. Over a 2-year period, serial CEA
      measurement thus yielded no patient benefit.

PMID- 10207737
TI  - Primary care research agenda: traveling the spectrum from efficacy to
      effectiveness.

PMID- 10207739
TI  - Priorities for agenda building: mental health and primary care.

PMID- 10207738
TI  - Mental health problems in primary care: a research agenda.
AB  - PURPOSE: The NAPCRG Task Force on Mental Health Problems was commissioned to
      explore critical research and policy issues in mental health and to develop a
      primary care research agenda for review and action by NAPCRG. This "White Paper"
      presents the key findings and recommendations of the Task Force. METHODS: A
      comprehensive review of the primary care mental health literature, using MEDLINE
      searches with manual follow up, and personal communications with many active
      researchers in the field were performed by the authors; Task Force members
      participated in the editing and refinement of the White Paper in a series of
      email and face-to-face meetings. SUMMARY AND CONCLUSIONS: Although primary care
      researchers have made major contributions to our growing understanding of mental
      health problems as they exist in the "real world" of primary care, rapid changes
      in the U.S. health care environment threaten to undo the integration of mental
      and physical health that is at the heart of primary care. It will be necessary
      for the primary care leaders in this field to step forward to guide policy
      makers, purchasers, and the public as primary care is reengineered for the next
      generation. Efforts to operationalize episode of care and comorbidity recording
      with EMR systems, particularly in cooperation with managed care corporations
      and/or primary care research networks, may represent the most effective strategy
      for promoting the integration of mental health services into primary care. The
      most promising area for research in the immediate future may be descriptive
      studies that capture and explore the clinical epidemiology of common mental
      health problems as they occur in routine practice.

PMID- 10207740
TI  - What factors influence the prescribing of antidepressant pharmacotherapy? An
      assessment of national office-based encounters.
AB  - OBJECTIVE: This study was designed to identify: 1) predictors of antidepressant
      pharmacotherapy among patients diagnosed with depression; and 2) predictors of
      prescription for either a selective-serotonin reuptake inhibitor (SSRI), or a
      serotonin-norepinephrine reuptake inhibitor (SNRI). METHOD: Data from the 1995
      National Ambulatory Medical Care Survey (NAMCS) were used to discern the number
      of office-based encounters documenting a diagnosis of depression (ICD-9-CM codes
      296.2-296.36; 300.4; or 311) among patients eighteen years of age or older.
      Logistic regression-derived odds ratios (OR) and 95 percent confidence intervals
      (CI) were used to elucidate factors predictive of receipt of antidepressant
      pharmacotherapy, and, more specifically, factors predictive of receipt of an SSRI
      or an SNRI. Model variables included age (18-49 years as compared to > or = 50
      years); race (white as compared to nonwhite, inclusive of Hispanics); gender;
      self-report of depression as a reason for the office-based encounter; and payer
      type (private insurance program as compared to public). RESULTS: Among the
      estimated 18,046,293 office-based visits resulting in a diagnosis of depression,
      56.2 percent of patients self-reported depression as a reason for the office
      based encounter; 67.5 percent were prescribed or continued a regimen of
      antidepressant pharmacotherapy; and 48.3 percent were prescribed an SSRI or an
      SNRI. Factors predictive of receipt of antidepressant pharmacotherapy included
      age less than fifty years (OR = 1.30, CI = 1.01-1.67); female gender (OR = 1.45,
      CI = 1.13-1.85); and self-report of depression as a reason for the office-based
      encounter (OR = 1.98, CI = 1.57-2.51). Factors predictive of receipt of an SSRI
      or an SNRI included age less than fifty years (OR = 1.31, CI = 1.03-1.65); female
      gender (OR = 1.55, CI = 1.23-1.95); and self-report of depression as a reason for
      the office-based encounter (OR = 1.56, CI = 1.25-1.95). In addition, having
      private insurance increased the likelihood of having been prescribed an SSRI or
      SNRI by 46 percent (OR = 1.46, CI = 1.13-1.89). CONCLUSIONS: Among patients with
      a diagnosis of depression, the pattern of prescribing antidepressant
      pharmacotherapy is influenced by a patient's age, gender, self-report of
      depression, and type of insurance coverage. Further research is required to
      discern the reasons for these observed effects and to advance clinically rational
      and equitable access to pharmacotherapeutic innovation.

PMID- 10207741
TI  - Characteristics and course of major depression in older primary care patients.
AB  - OBJECTIVE: Identify the morbidity patterns displayed by older primary care
      patients experiencing depressive symptomatology who do and do not meet criteria
      for a major depression. METHOD: Patients ages sixty and older presenting at two
      ambulatory internal medicine centers were administered the CES-D. Among those
      scoring > or = 11, 104 completed a comprehensive assessment of their psychiatric
      symptomatology, medical illness, and functional abilities. The assessment battery
      was again administered six months later. RESULTS: The point prevalence of major
      depression in older primary care patients is estimated at 9 percent based on SCID
      interviews. Patients meeting criteria for this diagnosis compared to those who
      are symptomatic but not experiencing a major depression described more extensive
      psychopathology but also significantly more limitations in performing social and
      functional roles. At six-month follow-up, only 11.5 percent of those initially
      diagnosed with a major depression were considered fully recovered. CONCLUSIONS:
      Major depression is a prevalent disorder in older primary care patients which
      affects their ability to perform expected social and physical roles. Mechanisms
      for delivering efficacious treatments in routine medical practice are of a high
      priority.

PMID- 10207742
TI  - Clock tests in depression, Alzheimer's disease, and elderly controls.
AB  - OBJECTIVE: While clock-drawing tests are commonly used to screen for cognitive
      impairment in the elderly, little is known about the performance of elderly
      depressives. METHODS: We compared thirty-three patients with major depression to
      forty-two Alzheimer's disease and thirty age-matched controls on clock-drawing,
      copying, and reading. RESULTS: Patients with Alzheimer's disease had
      significantly lower scores on clock-drawing, copying, and reading than patients
      with depression or the controls (p < 0.05). Patients with depression did not
      differ significantly from controls on quantitative scores or qualitative errors.
      CONCLUSIONS: Clock tests may be useful for identifying depressed patients with
      underlying dementia.

PMID- 10207743
TI  - Neuroticism, other personality variables, and serum lipid levels in patients with
      anxiety disorders and normal controls.
AB  - OBJECTIVE: This study evaluates the association between certain personality
      variables, especially neuroticism, and serum lipid levels in patients suffering
      from anxiety disorders as opposed to normal control individuals. It addresses the
      question whether in anxiety disorder patients neuroticism is associated with
      elevated serum cholesterol and serum LDL cholesterol levels. METHOD: Thirty (15
      male, 15 female) patients with anxiety disorders as defined by DSM-IV and thirty
      normal matched controls were enrolled in this study. The patients were either
      admitted for inpatient treatment or referred to the behavioral therapy outpatient
      clinic at the Department of Psychiatry of the University Hospital Eppendorf
      (Hamburg/Germany). Control individuals were selected on a voluntary basis and
      recruited from the authors' colleagues and peers. Matching included Body-Mass
      Index, age, and gender. RESULTS: This study showed a significant positive
      association of neuroticism and serum cholesterol (r = .29) and serum LDL
      cholesterol (r = .35) within the entire cohort of participants. An even higher
      significant positive relation (r = .43) could be detected between neuroticism and
      serum LDL cholesterol within the psychiatric patient group. As far as differences
      of personality variables between patients and normal controls are concerned,
      patients seemed to be significantly less satisfied with life, more generally
      inhibited, more irritable, more stressed, and more emotionally labile than
      controls. Anxiety disorder patients also tended to complain significantly more
      often about physical problems. CONCLUSIONS: Our data suggest that high scores of
      neuroticism in anxiety disorders patients may be involved in elevated serum LDL
      cholesterol levels and, thereby, may lead to an increased risk of coronary heart
      disease.

PMID- 10207744
TI  - Maladaptive denial of physical illness: a useful new "diagnosis".
AB  - OBJECTIVE: Denial of physical illness and/or refusal of treatment are critical
      issues in the practice of medicine. A previous article proposed DSM-IV consider a
      new diagnosis for a subgroup of patients who refuse treatment, i.e., maladaptive
      denial of physical illness [1]. It is necessary to be able to use this form of
      denial as a diagnosis rather than invoke the term denial as merely a mental
      mechanism. This is a report of a prospective descriptive study of psychiatric
      consultations for medical inpatients who deny that they are ill or who refuse
      treatment. METHOD: In order to investigate the utility of this proposed diagnosis
      we conducted a one year study of all psychiatric consultations at a community
      hospital in Manhattan, New York. RESULTS: The diagnosis of maladaptive denial of
      physical illness was made in 2.5 percent of 317 psychiatric consultations. The
      patients did not fit into other DSM-III-R or DSM-IV categories. CONCLUSIONS: We
      suggest a clarification of the concept of denial for use with medically ill
      patients. The findings in this study demonstrate that the current categories in
      DSM-IV do not provide physicians with a diagnosis that describes this particular
      type of pathological denial of illness.

PMID- 10207745
TI  - Why denial of physical illness is not a "diagnosis".

PMID- 10207746
TI  - Designing appropriate rehabilitation technology: a mobility device for women with
      ambulatory disabilities in India.
AB  - Mobility is an essential requirement for personal independence and social
      participation. For persons with an ambulatory disability, a lack of mobility
      creates barriers to the realization of these goals. In developed countries,
      significant research and development has resulted in the technological
      advancement of assistive devices. Unfortunately, transfer of these technologies
      to developing countries has proven difficult. Consequently, effort has been
      directed at designing appropriate technology in these countries--most often in
      the form of wheelchairs and hand-driven tricycles. For activities within and
      around the home, however, especially in cultures where many activities are
      traditionally performed on the floor, wheelchairs and tricycles are often
      inappropriate solutions. In response to this, a novel mobility device has been
      designed for use by women with ambulatory disabilities living in rural and low
      income areas of India. The device is intended to assist the user in performing
      activities of daily living which occur within and near the home, and at ground
      level. To this end, the device conceptually differs from traditional wheelchair
      designs in that it physically keeps the rider near to the floor. This paper
      describes the new device as well as the cross-cultural and cross-professional
      collaborative methodology used in its design.

PMID- 10207747
TI  - Neuropsychology and the relearning of motor skills following stroke.
AB  - Regaining independent mobility is one of the most important goals in physical
      therapy with patients suffering from the consequences of stroke. Both physical
      therapy and occupational therapy are learning processes in which the patient has
      to remaster old skills or has to learn novel skills. It is argued that the (re
      )learning of motor control is a process in which motor aspects continuously
      interact with sensory and cognitive processes. It is therefore necessary that
      neuropsychological knowledge should be integrated in the therapy in order to
      create the most optimal situation for learning. In this article the most
      prominent neuropsychological consequences are described and suggestions are given
      as to how a therapist may use this knowledge to improve the therapy.

PMID- 10207748
TI  - Psychosocial adaptation to amputation: the role of sociodemographic variables,
      disability-related factors and coping strategies.
AB  - This study examined the roles of sociodemographic variables, disability-related
      factors, and coping strategies as predictors of the psychosocial adaptation of 61
      persons with amputations. Psychosocial adaptation was conceptualized as a
      multifaceted outcome criterion and was measured by seven scales from the
      Reactions to Impairment and Disability Inventory (RIDI) and the Acceptance of
      Disability (AD) scale. A series of multiple regression analyses indicated that
      both a set of sociodemographic variables and disability-related factors (age,
      duration of amputation, type of amputation) and a set of coping strategies
      (action problem-solving, emotion-focusing, behavioral/problem disengagement,
      cognitive disengagement) accounted, albeit differentially, for significant
      portions of the variance in the outcome measures of psychosocial adaptation to
      amputation. Of the various coping strategies, active problem-solving was
      negatively associated with the psychosocial reactions of depression and
      internalized anger (RIDI) but it was positively associated to adjustment (RIDI)
      and acceptance of disability (AD). Emotion-focusing and cognitive disengagement
      were positively associated with anxiety, depression, and externalized hostility
      (RIDI) and negatively associated with acceptance of disability (AD). Measurement
      and theoretical implications are briefly outlined.

PMID- 10207749
TI  - Sustaining and improving working capacity--programme description and two years
      follow-up.
AB  - In 1991 the Social Insurance Institution Rehabilitation Act introduced a working
      capacity sustaining and improving training programme (TYK). The goal of this
      programme is to sustain the physio-psycho-social competences of older workers and
      employees by creating a chain of in-house rehabilitation phases and training
      phases at the workplace. We describe the programme in its early state of
      implementation. Two years after entering the programme 17 patients were working,
      six were on sick leave, three were out of work, 16 were on pension, and six
      patients could not be retrieved.

PMID- 10207751
TI  - Sexual dysfunction of persons after traumatic brain injury: perceptions of
      professionals.
AB  - The purpose of this paper was to study the perceptions of professionals in the
      field of rehabilitation in Israel concerning sexual dysfunction of persons after
      traumatic brain injury. Thirty professionals filled out an open-ended
      questionnaire that focused on problems of sexual functioning, dyadic and social
      relationships, and suggestions for the most appropriate interventions for these
      problems. The results indicated that for persons with TBI, the physical changes
      were not identified as the primary obstacle preventing persons after TBI from
      achieving sexual satisfaction, but rather the cognitive and emotional sequelae of
      TBI. A number of possible intervention techniques were also suggested.

PMID- 10207752
TI  - Interindividual differences in cognitive remediation research with schizophrenic
      patients--indicators of rehabilitation potential?

PMID- 10207750
TI  - Integration in Spain: national and regional perspectives.
AB  - At the present moment Spanish psychopedagogical researchers are evaluating the
      effectiveness and consequences of integration on both a national and a regional
      level. As a result of two important pieces of legislation, physically and
      mentally handicapped people are gradually becoming more integrated in education,
      social life, and the work place. Consequently, both ordinary pupils and those
      with permanent or temporary special education needs can achieve the same
      objectives within the same system. Individual strategies are designed to cope
      with each pupil's specific needs, and each case is followed closely by a
      multidisciplinary team. The basic concept behind integration in Spain is a global
      relationship with the educational environment, which includes school, home,
      vocational training and ultimately work. It is not so much a case of identifying
      what a pupil is, but rather deciding what education can do for that particular
      pupil. There are, however, certain difficulties which require adaptation of the
      curriculum: access to educational opportunities and experiences may be affected
      by deficient visual, auditory or motor skills; there may be an absence of
      specific learning skills in certain areas of the curriculum; pupils with serious
      mental handicaps may lack basic cognitive skills. Spanish educational reform
      considers the classroom teacher as the central axis in the quality of education.
      For this reason, new programmes and diplomas in infant and primary teacher
      education include training for adaptation and integration.

PMID- 10207753
TI  - The effect of placement in a hostel on the post-hospitalization rehabilitation of
      psychiatrically disabled persons in Israel.

PMID- 10207754
TI  - Scoring transfer and locomotion independence of home care patients: Barthel
      versus functional independence measure.

PMID- 10207755
TI  - Lower limb amputee patients' satisfaction with information and rehabilitation.

PMID- 10207756
TI  - A programme for the enhancement of autonomy in young adults with physical
      disabilities: the development of a realistic self concept, individual perception
      of quality of life and the development of independent living skills.

PMID- 10207757
TI  - Analysis of audiological services in Nigeria.

PMID- 10207758
TI  - What is the optimal anti-incontinence procedure in women with advanced prolapse
      and 'potential' stress incontinence?

PMID- 10207759
TI  - The influence of bladder volume on the position and mobility of the
      urethrovesical junction.
AB  - The influence of bladder volume on the position, mobility and funneling of the
      bladder neck and proximal urethra was determined by transperineal ultrasound in a
      prospective comparative clinical study at Dunedin Hospital, Dunedin, New Zealand.
      One hundred and nine women underwent urodynamic assessment, either as part of the
      investigation of urinary incontinence or as follow-up after incontinence
      correcting surgery. Bladder neck descent, retrovesical angle, rotation of the
      proximal urethra, and simple and extensive funneling/opening of the proximal
      urethra on Valsalva maneuver were assessed using ultrasound imaging at
      approximately 50 ml bladder volume and maximum bladder capacity (mean 355 ml,
      range 125-470 ml). The position of the bladder neck at rest was slightly higher
      at 50 ml than at maximum capacity (50 ml: 2.6 +/- 0.4 cm, max. cap. 2.5 +/- 0.4
      cm; P = 0.003) and it descended further with the Valsalva maneuver (50 ml: 1.9 +/
      1.2 cm, max. cap. 1.7 +/- 1 cm; P = 0.004). There was also a higher degree of
      urethral rotation (50 ml: 41 +/- 30 degrees, max. cap. 39 +/- 20 degrees) with an
      empty bladder (P = 0.072). As regards funneling of the bladder neck on Valsalva,
      equivalent results were obtained for 90 patients. In 19 cases there were
      discrepancies (Cohen's kappa 0.64). For extensive funneling to the midurethra the
      respective numbers were 83 and 26 (kappa 0.41). Generally simple and extensive
      funneling was more frequently seen with a full rather than an empty bladder,
      simple funneling being diagnosed in an additional 14 cases (P = 0.06) and
      extensive funneling in an additional 19 (P = 0.03). It was concluded that bladder
      filling influences the position and mobility of the bladder neck and the proximal
      urethra, which are both more mobile when the bladder is nearly empty. Funneling
      of the proximal urethra, however, is more easily observed with a full bladder.
      Imaging of the lower urinary tract should be undertaken at defined bladder
      volumes.

PMID- 10207760
TI  - Treatment of female urinary incontinence with EMG-controlled biofeedback home
      training.
AB  - The aim of the study was to evaluate the efficacy of pelvic floor training with
      EMG-controlled home biofeedback in the treatment of stress and mixed incontinence
      in women. Subjects were recruited from the urodynamic outpatient clinic and
      performed pelvic muscle training with an EMG-controlled biofeedback device for 20
      minutes daily for 6 months. The number of pads used per day, the number of
      incontinence and urgency episodes, voiding frequency, maximum urethral closure
      pressure, functional urethral length and pressure/transmission ratio during
      stress were assessed before and after treatment. Thirty-three patients (13 with
      stress and 20 with mixed incontinence) completed the study. There was a
      significant decrease in the number of pads used per day, the number of
      incontinence and urgency episodes, and the voiding frequency. Twenty-eight
      patients (85%) reported that they were cured or improved. Urodynamic parameters
      did not change significantly. It was concluded that home pelvic floor training
      with EMG-controlled biofeedback is efficient in 85% of patients in alleviating
      the symptoms of genuine stress and mixed incontinence without causing side
      effects.

PMID- 10207761
TI  - Relationship between surgically induced neuropathy and outcome of pelvic organ
      prolapse surgery.
AB  - The aim of the study was to determine whether surgically induced perineal
      neuropathy relates to the outcome of surgery for the correction of pelvic organ
      prolapse. Perineal nerve terminal motor latencies (PeNTML) were obtained in 31
      women prior to and following transvaginal surgery for the correction of pelvic
      organ prolapse consisting of bilateral sacrospinous ligament vault suspension and
      bilateral paravaginal cystocele repair. Mean follow-up was 32 months (range 12
      60). Surgical outcome was defined as optimal (asymptomatic, with the apex of the
      vagina above the levator plate with no tissue protruding beyond the hymen in the
      upright position with maximum Valsalva), or suboptimal (apical descent of > 50%,
      or any vaginal wall protrusion beyond the hymen in the upright position with
      maximum Valsalva). Surgically induced neuropathy was defined as an increase of
      0.6 ms or more in the averaged right and left PeNTML measurements following the
      surgery. All women had preoperative symptomatic prolapse and the mean
      preoperative PeNTML was prolonged compared to established normals. Using strict
      definitions, 11 women had optimal outcome and 20 had suboptimal outcome. The
      outcome groups were similar with respect to age, weight, parity, degree of
      preoperative prolapse and preoperative perineal neuropathy. Eleven women had
      surgically induced perineal neuropathy. This was associated with suboptimal
      outcome compared to optimal outcome (P = 0.03). The relative risk of suboptimal
      outcome with surgically induced neuropathy was 1.82 (95% CI 1.13-2.93). It was
      concluded that a relationship exists between the outcome of organ prolapse
      surgery and surgically induced perineal neuropathy as measured by PeNTML. Such
      neuropathy may play a role in failed pelvic reconstructive surgery.

PMID- 10207762
TI  - Suture injury to the urinary tract in urethral suspension procedures for stress
      incontinence.
AB  - The case histories of women attending the Urogynecology Department at the Royal
      Women's Hospital and Mercy Hospital for Women were reviewed between 1986 and 1998
      to determine the incidence and postoperative morbidity caused by suture injury to
      the urinary tract following urethral suspension surgery for stress incontinence.
      In our department 1103 Burch colposuspensions and 61 Stamey urethral suspensions
      have been performed. Intraoperative cystourethroscopy was performed routinely for
      the early detection and treatment of urinary tract injury. Intravesical sutures
      were found by routine intraoperative cystoscopy in 1 Stamey suspension, 1 open
      Burch colposuspension and 3 laparoscopic Burch colposuspensions. Ureteric suture
      ligation was diagnosed in 2 women intraoperatively and 1 women postoperatively
      after laparoscopic Burch colposuspension. Two women presented with late
      complications from intravesical sutures following open Burch colposuspension. A
      further 7 women referred with urinary symptoms were found to have intravesical
      sutures, 2 following Burch colposuspension, 4 following Stamey urethral
      suspension and 1 following the Marshall-Marchetti-Kranz procedure. Seven of the 9
      women diagnosed with intravesical sutures presented with bladder or pelvic pain,
      frequency or urinary tract infection. Two women had recurrent stress incontinence
      and were found to have a intravesical suture on routine cystoscopy at the time of
      stress incontinence surgery. Suture removal, with any accompanying calculus, was
      achieved cystoscopically with almost immediate resolution of symptoms without
      loss of urinary control in all cases. Non-absorbable intravesical sutures
      occurring as a result of suture misplacement or erosion is an infrequent but
      important complication of stress incontinence surgery, but should be suspected if
      pain and irritative bladder symptoms or recurrent urinary infection occur
      postoperatively. Cystourethroscopy performed intra-operatively or postoperatively
      is essential for early diagnosis and treatment.

PMID- 10207763
TI  - Dietary caffeine, fluid intake and urinary incontinence in older rural women.
AB  - Forty-one women completed the first phase (self-monitoring) of the Behavioral
      Management for Continence (BMC) intervention, while working with a nurse during
      home visits to reduce involuntary urine loss as part of the parent study
      involving older, rural women living at home. A decrease in dietary caffeine
      intake and an increase in fluid intake were most frequently recommended. The
      relationship between a decrease in the amount of dietary caffeine consumed and
      fewer daytime episodes of involuntary urine loss approached significance -P =
      0.0744- whereas an increase in the average amount of fluid intake was
      significantly related to an increase in the average volume of urine voided -P =
      0.0479- and not to involuntary urine loss.

PMID- 10207764
TI  - An anatomical classification--a new paradigm for management of urinary
      dysfunction in the female.
AB  - A new classification specifies anatomical defects in the anterior, middle and
      posterior zones of the vagina as causing urinary dysfunction. An external
      musculoelastic mechanism stretches the vagina to open and close the outflow
      tract. The same pelvic floor muscles provide a peripheral control mechanism for
      micturition. The stretched vagina prevents the filling bladder from activating
      the stretch receptors. Vaginal laxity may weaken the transmission of muscle
      forces, interfering with the mechanical process of opening and closure. Laxity
      may also destabilize the peripheral control mechanism, a neurological process,
      causing bladder control to swing between the open and closed modes, i.e. bladder
      instability. Specific symptoms, signs and urodynamic tests were arranged into a
      pictorial algorithm as a practical guide for locating the three zones of
      anatomical defects. It was possible to reinterpret almost all the definitions and
      descriptions of the International Continence Society in terms of this
      classification, and to explain how vaginal laxity may cause premature activation
      of the micturition reflex (detrusor instability), stress incontinence and
      abnormal emptying (dribble, overflow). This convergence in anatomical and
      urodynamic (ICS) concepts explains many previously unexplained phenomena, and
      potentially opens up an entirely new approach to management, non-surgical
      strengthening of specific ligaments, or surgical reinforcement thereof with
      ambulatory 'keyhole' methods which do not require catheterization.

PMID- 10207765
TI  - A unique cause of unconscious urinary incontinence.
AB  - The authors present a case of a healthy 55-year-old woman with a 1-year history
      of vaginal malodor and perineal dampness. A pyridium (phenazopyridine) pad test
      revealed a well-defined stain area no greater than 3 cm. Cystoscopic examination
      revealed multiple multilobulated polypoid neoplasms, which we feel probably
      represent pedunculated hemangiomas. Removal of the neoplasms cured the dampness,
      malodor and recurrent vaginal infections. We submit this case as a unique cause
      of extraurethral incontinence.

PMID- 10207766
TI  - Metastatic breast cancer diagnosed during a work-up for urinary incontinence: a
      case report.
AB  - Breast cancer is the most commonly diagnosed cancer among women in the USA and
      the second leading cause of cancer deaths in women. Breast cancer metastases to
      the bladder are unusual but have been reported occasionally in the literature.
      The majority of the reports describe bladder metastases presenting with
      symptomatology or occurring in the context of disseminated disease. We present
      the case of an 87-year-old woman with a history of breast cancer and negative
      routine work-up for metastatic disease. She was referred to the urogynecology
      division in our institution because of complaints of urinary incontinence and
      urinary urgency. A urethrocystoscopy revealed suspicious bladder mucosal lesions
      that were biopsied. The pathology findings, when compared to the original cancer
      specimens, were consistent with metastatic disease. This case suggests that in
      patients with a history of breast cancer, even subtle urinary symptoms should be
      thoroughly evaluated.

PMID- 10207767
TI  - Fluid balance therapy of nocturia in women.
AB  - Nocturia is a common and troublesome symptom in otherwise healthy elderly men and
      women. Nocturnal polyuria (an excessive nighttime urine output) has been
      documented to be a common finding in healthy men with lower urinary tract
      symptoms. It is also a presenting feature of various medical conditions, such as
      renal failure, hypercalcemia and diabetes. Fluid balance therapy is an option in
      those whose nocturia is secondary to nocturnal polyuria. If a reduction in fluid
      intake fails to reduce nocturnal frequency a variety of drug treatments may be
      beneficial. Several studies have confirmed the efficacy of intranasal DDAVP, a
      synthetic analog of antidiuretic hormone, in both healthy patients and those with
      neuropathic bladders, although fluid overload and hyponatremia are potential side
      effects. Other drug treatments include early evening diuretics, such as frusemide
      or bumetanide. More recently imipramine has shown therapeutic benefit in young
      adults with enuresis, and might prove to be useful in the elderly with nocturnal
      polyuria.

PMID- 10207768
TI  - Psychological investigation in female patients suffering from urinary
      incontinence.

PMID- 10207769
TI  - Trends in the antimicrobial susceptibility of bacterial respiratory tract
      pathogens--findings of the Alexander Project 1992-1996.
AB  - The Alexander Project is an ongoing, multicenter surveillance study of the
      antimicrobial susceptibility of community-acquired lower respiratory tract
      bacterial pathogens with testing undertaken in a central laboratory. During the
      period 1992-1995, isolates were collected from geographically separate centers in
      countries of the EU and various states in the USA. In 1996, the project was
      extended to centers in Mexico, Brazil, Saudi Arabia, South Africa, Hong Kong and
      other European countries not previously included. Within Europe, France and Spain
      are established as centers with a high prevalence of both penicillin-intermediate
      (MIC 0.12-1 mg/l) and resistant (MIC > or = 2 mg/l) strains of Streptococcus
      pneumoniae, with combined resistance rates in excess of 40% in Toulouse and
      Barcelona in 1996. Combined rates of intermediate and resistant strains in excess
      of 10% were found in 1996, the first year of sampling, in Belgium, Switzerland,
      the Slovak Republic and Hungary. Penicillin resistance has evolved in the USA
      during the period of study, with rates for combined pneumococcal isolates
      increasing from 5.6% in 1992 to 16.4% in 1996. Of the new, non-European centers
      joining the project in 1996, Mexico (intermediate 31.4%, resistant 15.7%) and, in
      particular, Hong Kong (intermediate 9.1%, resistant 50%) are centers with a high
      prevalence of penicillin resistance. Macrolide resistance has increased generally
      among pneumococcal isolates examined during the study period, both in penicillin
      susceptible and resistant isolates, and was evident in 16.5% of the 2160 isolates
      collected during 1996. In four centers (London, UK; Genoa, Italy; Pokfulum, Hong
      Kong; Leuven, Belgium), macrolide resistance rates exceeded those of combined
      penicillin-intermediate and resistant strains; in 12/19 centers (63.2%) macrolide
      resistance was more prevalent than penicillin resistance. In 1996, macrolide
      resistance was found in excess of 10% of isolates in Poland, Hungary, London, UK,
      combined USA isolates, the Slovak Republic, Barcelona, Spain, Genoa, Italy,
      Mexico, Toulouse, France and Pokfulum, Hong Kong. beta-lactamase production was
      the principal mechanism of resistance found among isolates of Haemophilus
      influenzae, with rates in 1996 of around 20% or more in France, Belgium and
      Spain, and in excess of 10% in the UK and the Czech Republic. In the same year in
      non-European centers, Mexico (25%), Saudi Arabia (27.9%), Hong Kong (37.1%) and
      the USA (30.4% of combined isolates) had a high prevalence of beta-lactamase
      production. Isolates of beta-lactamase-negative, ampicillin-resistant H.
      influenzae were generally very uncommon, with only Barcelona, Spain consistently
      associated with rates in excess of 1%. beta-lactamase production in Moraxella
      catarrhalis was observed in over 90% of isolates tested in 1996.

PMID- 10207770
TI  - Chairman's introduction--the importance of good quality surveillance data today.
AB  - The Alexander Project is a continuing, international, multicenter, longitudinal
      study of the antimicrobial susceptibility of pathogens commonly associated with
      community-acquired lower respiratory tract infections (LRTI). The study began in
      1992 to provide high-quality surveillance data, comparable between regions and
      through time. As antimicrobial resistance becomes more prevalent, reliable
      surveillance data are required for clinical decision-making. Accurate current
      susceptibility data are required to predict clinical success through the
      determination of pharmacodynamic breakpoints. The Alexander Project provides the
      information required for clinicians to improve the likelihood of microbiological
      and clinical cure in the antibiotic treatment of LRTI.

PMID- 10207771
TI  - Assessing the quality of the Alexander Project.
AB  - Controlled, standardized methods and quality control strains should be used in
      order to ensure that susceptibility data is valid and reproducible. Small
      differences in the methods used can lead to important variations in the results
      obtained. Comparisons between related agents and between studies, using
      statistical analysis, also indicate whether susceptibility data are consistent
      with known antimicrobial-organism relationships. The Alexander Project has
      demonstrated a consistently high level of quality, allowing the comparison of
      susceptibility data from over 27,500 organisms isolated from patients with lower
      respiratory tract infection.

PMID- 10207772
TI  - Evolving resistance patterns of Streptococcus pneumoniae: a link with long-acting
      macrolide consumption?
AB  - The Alexander Project indicates an increase in the prevalence of S. pneumoniae
      resistance to macrolide antibiotics. In some centers, the prevalence of S.
      pneumoniae macrolide resistance exceeds that of penicillin resistance. Centers
      with a high level of macrolide resistance tend to also have high levels of
      penicillin resistance. Antimicrobial use may be an important driver of
      resistance. The application of pharmacodynamic concepts suggests that bacterial
      exposure to low and prolonged concentrations of macrolides may have a role in the
      selection of resistance. Analysis of macrolide prescribing and resistance
      patterns indicates a correlation between increasing macrolide resistance and the
      increased use of newer, long-acting macrolides, although further study is
      required to investigate the causality of this correlation. In order to attempt to
      prevent the further spread of resistance, antibiotic choice should maximize the
      opportunity for bacterial eradication.

PMID- 10207773
TI  - Resistance patterns of Haemophilus influenzae.
AB  - Haemophilus influenzae is an important respiratory tract pathogen, and the
      prevalence of strains resistant to the antibiotics used to treat it has increased
      since the 1970s. Data on H. influenzae have been gathered in the Alexander
      Project, an ongoing, international surveillance study. They reveal that beta
      lactamase production is the primary mechanism for H. influenzae resistance and
      that the resistance has a wide geographical variation, reaching critical levels
      in some countries. Unlike many techniques used in the past, Alexander Project
      methods provide accurate, reproducible susceptibility data, allowing the
      comparison of resistance prevalence over time and between areas. Traditional
      antimicrobial breakpoints are being superseded by more accurate and clinically
      relevant methods of predicting drug efficacy, such as time above the MIC, AUC:MIC
      ratios and pharmacodynamic breakpoints. Continued surveillance for resistance and
      susceptibility testing of H. influenzae is vital to maximize the benefits of
      antimicrobial therapy and to contain the spread of infection.

PMID- 10207774
TI  - Basing empiric treatment choices for respiratory tract infection on the results
      of the Alexander Project.
AB  - For respiratory tract infection (RTI), antibiotics should have proven clinical
      efficacy against the major pathogens involved-Streptococcus pneumoniae,
      Haemophilus influenzae and Moraxella catarrhalis. As the pattern of resistance to
      antimicrobials changes, the clinical effectiveness of these agents should be
      reviewed. However, clinical trials are time consuming and costly, and alternative
      ways of predicting clinical efficacy using susceptibility data have been
      investigated. Pharmacodynamic breakpoints have been suggested as providing the
      link between susceptibility data and clinical effectiveness and this is supported
      by emerging clinical evidence. Thus, using the data collected in the Alexander
      Project, guidelines for the treatment of RTI can be developed which reflect the
      local resistance profile and maximize the chances of clinical success.

PMID- 10207775
TI  - TT virus: an agent of transfusion-associated hepatitis or yellow herring?

PMID- 10207776
TI  - Discovery of vitamin B12 in the liver and its absorption factor in the stomach: a
      historical review.
AB  - This review describes the early chronological events in the pursuit of a
      treatment for pernicious anaemia, and the subsequent discovery of vitamin B12 and
      the intrinsic factor. It details Castle's experiments which established the
      theory of extrinsic and intrinsic factors as hemopoietic principles, and
      describes the studies on purification of the anti-pernicious anaemia principle
      from liver tissue that terminated in the crystallization of vitamin B12 and
      identification of its coenzyme forms. Biochemical purification and
      characterization of the intrinsic factor secreted by the gastric parietal cells,
      and two other vitamin B12 proteins, R-binder (transcobalamin I, haptocorrin), and
      transcobalamin II, are discussed in detail. The biochemical reactions in micro
      organisms and humans in which vitamin B12 is involved are then briefly reviewed,
      and finally and briefly the immunological basis of pernicious anaemia is
      discussed.

PMID- 10207777
TI  - [14C]-urea breath test to confirm eradication of Helicobacter pylori.
AB  - BACKGROUND: Treatment for Helicobacter pylori reduces ulcer recurrence.
      Eradication rates of the organism vary with different drug regimens from 30% to
      90%. There is a need to identify patients who have failed treatment. [14C]-Urea
      breath test (UBT) is non-invasive, sensitive, safe and highly reliable test for
      diagnosis of H. pylori infection. As there is a paucity of reports on the utility
      of [14C]-UBT in confirming H. pylori eradication, this study was undertaken.
      METHODS: Thirty-eight patients (age 34 +/- 17 years, range 16-84 years, 27 men)
      with upper gastrointestinal symptoms underwent upper gastrointestinal endoscopy.
      Baseline H. pylori infection was diagnosed by identification of the organism on
      antral biopsies and positive rapid urease test (RUT). After 1 month of completion
      of treatment, repeat RUT and histological examination of antral endoscopic
      biopsies were performed. Eradication of H. pylori was defined as absence of the
      organism on histology, and negative RUT. The [14C]-UBT was performed using 185
      kBq [14C]-urea dissolved in 300 mL water. Breath samples were collected once
      before ingestion of [14C]-urea, and subsequently at 5 and 15 min. Results were
      expressed as 14CO2/mmol CO2 exhaled as per cent of administered urea. RESULTS:
      Endoscopy revealed antral gastritis (n = 14), duodenal ulcer (n = 8), duodenitis
      (n = 2), oesophagitis (n = 1), antral gastritis and duodenal ulcer (n = 3),
      antral gastritis and duodenitis (n = 7) and normal upper gastrointestinal
      endoscopy (n = 3). All the 20 patients who were negative for H. pylori on RUT and
      histology, tested negative for H. pylori on [14C]-UBT. However, of 18 patients
      shown to have H. pylori infection on RUT and histology, 16 were positive for H.
      pylori on [14C]-UBT. The sensitivity, specificity, positive predictive value,
      negative predictive value and accuracy of [14C]-UBT were 100, 89, 91, 100 and 95%
      respectively. CONCLUSIONS: The [14C]-UBT is a reliable indicator of H. pylori
      eradication after treatment. It can obviate the need for antral biopsies to
      confirm eradication of H. pylori after completion of treatment.

PMID- 10207778
TI  - Helicobacter pylori in Meckel's diverticulum with heterotopic gastric mucosa in a
      population with relatively high H. pylori prevalence rate.
AB  - BACKGROUND: Helicobacter pylori (H. pylori) colonize only foveolar gastric-type
      mucosa and are associated with active chronic gastritis and peptic ulcer. The aim
      of this study was to investigate whether H. pylori can also be found in Meckel's
      diverticulum which contains heterotopic gastric mucosa. METHODS: Biopsy specimens
      of Meckel's diverticulum resected in Queen Mary Hospital, University of Hong
      Kong, during the 10 year period 1986-1995 were retrieved and reviewed. Those
      containing gastric heterotopia were examined for the presence of H. pylori, using
      Warthin-Starry silver stain. RESULTS: In the 59 cases of Meckel's diverticula
      studied, 16 were found to contain heterotopic gastric mucosa. Helicobacter pylori
      were not identified in any of these cases. In one of the 16 patients a
      concomitant gastric biopsy was performed. Although the gastric mucosa of this
      patient was heavily colonized by H. pylori, again no H. pylori was found in the
      heterotopic gastric mucosa in the Meckel's diverticulum. CONCLUSIONS: The absence
      of H. pylori in all the Meckel's diverticula examined, even when the stomach was
      heavily colonized by the organisms, suggests that colonization of Meckel's
      diverticulum by H. pylori is a rare event. This, together with the overall rarity
      of H. pylori in all reported series of Meckel's diverticulum, argues against its
      causative role in complications of Meckel's diverticulum.

PMID- 10207779
TI  - Efficacy of 1 week omeprazole or lansoprazole-amoxycillin-clarithromycin therapy
      for Helicobacter pylori infection in the Japanese population.
AB  - BACKGROUND: The effectiveness of curative therapy for Helicobacter pylori may
      vary according to the geographic region and patient population, thus the efficacy
      of each treatment regimen should be determined according to the specific patient
      population. However, there is no literature available concerning the efficacy of
      1 week omeprazole-amoxycillin-clarithromycin (OAC) regimens for the cure of H.
      pylori infection in Japan. METHODS: Helicobacter pylori-positive patients (224)
      with peptic ulcer disease or non-ulcer dyspepsia were randomized to receive one
      of three different omeprazole or lansoprazole-amoxycillin-clarithromycin (PPI/AC)
      regimens for 7 days: (1) OAC 20 regimen (n = 76), omeprazole (OPZ) 20 mg daily,
      amoxycillin (AMOX) 500 mg t.d.s. and clarithromycin (CAM) 200 mg b.d.; (2) LAC 30
      regimen (n = 73), Lansoprazole (LPZ) 30 mg daily, AMOX 500 mg t.d.s. and CAM 200
      mg b.d.; and (3) OPZ 40 regimen (n = 75), OPZ 20 b.d., AMOX 500 mg t.d.s. and CAM
      200 mg b.d. Cure of the infection was determined by the [13C]-urea breath test, 1
      month after completion of the treatment. RESULTS: Intention-to-treat based cure
      rates for OAC 20, LAC 30 and OAC 40 regimens were 75.0% (95% CI, 64-84%), 82.2%
      (95%, CI 72-90), and 80.0% (95% CI, 69-88), respectively and per-protocol based
      cure rates of these regimens were 79.2% (95% CI, 68-88%), 83.3% (95%, CI 73-91),
      and 83.1% (95% CI, 72-91%), respectively. Adverse effects, which included
      diarrhoea, glossitis or skin rash, were reported by 26.1% of the patients.
      However, these were mild and did not affect compliance. CONCLUSION: One week
      PPI/AC regimens for H. pylori infection with smaller proton pump inhibitors and
      antimicrobial dosages compared to regimens used in Western countries were
      revealed to provide sufficient cure rate (more than 80% by ITT analysis) with
      mild adverse effects in the Japanese population.

PMID- 10207781
TI  - Detection of telomerase activity in biopsy samples of colorectal cancer.
AB  - BACKGROUND: Telomerase is a ribonucleoprotein that synthesizes telomeric DNA onto
      chromosomal ends. The expression of telomerase is thought to be required for
      cellular immortality and oncogenesis. METHODS: To investigate the role of
      telomerase in the pathogenesis of colorectal cancer, we analysed telomerase
      activity in biopsy samples of colorectal cancer and colonic adenomas. Using a
      polymerase chain reaction-based assay, we examined telomerase activity in 52
      samples of colorectal cancer, 12 colonic adenomas and 30 normal colonic mucosa
      samples obtained by endoscopic biopsy. RESULTS: Telomerase activity was
      detectable in 88.5% (46/52) of colorectal carcinomas, in 50% (6/12) of colonic
      adenomas but not in normal colorectal mucosa. There was no correlation between
      telomerase activity and tumour location, type, size and differentiation (P >
      0.05). CONCLUSIONS: It was concluded that telomerase activation plays a role in
      the evolution of colorectal cancer, and that measurement of telomerase activity
      in biopsied colorectal mucosa samples may provide information both as a
      diagnostic marker to detect small numbers of cancer cells, and as a screening
      method for patients at high risk for colorectal carcinoma.

PMID- 10207780
TI  - Rapid elimination of Helicobacter pylori and reduction of histocompatibility
      leucocyte antigen-DR expression 12 h after a single dose of omeprazole,
      amoxycillin and metronidazole triple therapy.
AB  - BACKGROUND: Studies of eradication of Helicobacter pylori and subsequent
      resolution of H. pylori-related gastritis, have focused mainly on medium and long
      term change following eradication therapies. Results from those studies have
      shown that both acute and chronic inflammatory changes found in gastric mucosa
      eventually return to normal. However, the early events in the stomach,
      particularly the effects on bacterial density and acute inflammatory markers of
      anti-H. pylori treatment, are largely unknown. The objective of this study was
      therefore to examine changes in the number of H. pylori, and the severity of
      gastric mucosal inflammation in the gastric biopsy specimens of patients before
      (0 h group, n = 14) and 12 h (12 h group, n = 14) after initiating anti-H. pylori
      treatment. METHODS: Biopsies were assessed, either quantitatively or semi
      quantitatively, for the presence of H. pylori, neutrophils, mast cells,
      intraepithelial lymphocytes and the expression of histocompatibility leucocyte
      antigen (HLA)-DR by gastric epithelium and the results were compared between
      groups. RESULTS: Median H. pylori scores were 5 (range 2-5) and 0 (range 0-2) in
      biopsies from untreated and 12 h post-treatment groups, respectively (P < 0.001).
      In most 12 h post-treatment biopsies, H. pylori organisms could not be
      identified. There was a significant reduction in HLA-DR expression by gastric
      epithelium (median 3.5 with range 2-4 at 0 h group vs median 2 with range 0-4, P
      < 0.05), but there was no significant difference in the number of intraepithelial
      lymphocytes, CD3+ cells, mast cells or the distribution and density of
      neutrophils (all P > 0.05). Furthermore, the severity of gastritis as scored with
      the Sydney system was similar in both untreated and treated groups. CONCLUSIONS:
      The results of this study indicate that elimination of H. pylori organisms and
      resolution of some inflammatory markers occurs as early as 12 h following a
      single dose of omeprazole 40 mg, amoxycillin 1.0 g and metronidazole 400 mg,
      which suggests that rational therapeutic strategies with shorter duration using
      the currently available drugs may be possible.

PMID- 10207782
TI  - An analysis of T cell antigen receptor variable beta genes during the clinical
      course of patients with chronic hepatitis B.
AB  - BACKGROUND: The degree of hepatocyte injury in patients with chronic hepatitis B
      appears consistent with the number of T cells that respond to hepatitis B virus
      related antigens. METHODS: By using a polymerase chain reaction (PCR)-based
      approach, we monitored a ratio of the T cell antigen receptor (TcR) variable (V)
      beta gene families against a total TcR V beta gene expression in the peripheral T
      cells obtained from five patients and four healthy controls. RESULTS: In the
      healthy controls, there was no significant change in the ratios at an interval of
      four or eight weeks. In contrast, several TcR V beta families showed the
      significant changes in the ratios of their gene expression during the follow-up
      period in all patients. No common highly fluctuated TcR V beta, however, was
      found among the patients. Furthermore, there was no correlation between their
      changes and serum levels of alanine aminotransferase. CONCLUSIONS: These findings
      suggest that the skewing of the TcR family with multiclone is the result of T
      cell responses to viral antigens in peripheral blood.

PMID- 10207783
TI  - Characterization of anti-hepatitis C virus-positive sera not genotyped by
      restriction fragment length polymorphism or serology.
AB  - BACKGROUND: The hepatitis C virus genome is extremely heterogeneous and has been
      classified into six major genotypes. Genotyping of hepatitis C has been achieved
      through both direct molecular approach and indirect detection of host genotype
      specific antibodies by serological methods. The purpose of this study was to
      characterize anti-hepatitis C positive sera samples that were not genotyped
      either by restriction fragment length polymorphism or by serology. METHODS: Two
      hundred and two patients from northern California with established chronic
      hepatitis C virus infection were studied by restriction fragment length
      polymorphism analysis of the 5'-untranslated region amplicon. A serological
      genotyping assay, based on synthetic peptides derived from non-structural region
      4 of the hepatitis C virus genome, was used to determine serological genotype.
      RESULTS: Of the 202 patients studied, 187 (93%) were polymerase chain reaction
      positive. One hundred and eighty-six patients were able to be genotyped by
      restriction fragment length polymorphism, compared with 144/202 (71%) of patients
      genotyped by serology (P < 0.0001). Only two of 202 samples showed discordant
      genotyping results. The distribution of hepatitis C virus genotypes in northern
      California was found to be type 1a, 41%; 1b, 35%; 2a, 3%; 2b, 10%; 3a, 11%; and
      4, < 1%. There was no association between hepatitis C genotypes and age, gender
      distribution, ethnic origin, presumptive mode of transmission, serum alanine
      aminotransferase levels and the proportion of patients with cirrhosis. Of the 15
      patients who were not genotypable by the molecular assay, four patients were
      genotyped by serology, with hepatitis C virus genotypes 1, 2 and 3 represented.
      Of the 58 samples that were not genotyped by serology, 47 were genotyped based on
      the molecular assay, and the distribution of hepatitis C virus genotypes was
      similar to that of the overall study population. CONCLUSIONS: These data showed
      that: (i) molecular genotyping assay based on 5'-untranslated region is more
      sensitive than serologic genotyping based on the non-structural-4 region but the
      results were highly concordant; (ii) hepatitis C virus genotypes 1-4 are present
      in northern California, with genotype 1 being the most prevalent; and (iii) the
      failure to determine hepatitis C virus genotype based on molecular or serological
      genotyping assay does not appear to be related to specific hepatitis C genotypes.

PMID- 10207784
TI  - Relationship between the effect of interferon therapy and the change of hepatitis
      C virus non-structural 5B gene.
AB  - BACKGROUND: Hepatitis C virus (HCV)-RNA titre has been regarded as a factor
      affecting the response to interferon (IFN) therapy of patients with chronic
      hepatitis C (CHC). The focus of our study is the investigation of the nucleotide
      sequence of HCV-RNA NS5B, which may code RNA-dependent RNA polymerase and NS5A in
      the sera of 33 patients with CHC prior to IFN therapy. METHODS: Hepatitis C virus
      genotype and HCV-RNA titre were examined by polymerase chain reaction (PCR) and
      competitive reverse transcriptase-PCR. RESULTS: The sequence for HCV-RNA NS5B (nt
      8331-8600 in 1b and 8410-8679 in 2a) was determined by direct sequencing. The
      changes of the predicted amino acids in the genotype-specific sites of HCV-J, HCV
      BK, HC-J4/83, HCV-JT, HCV-N, HC-J6 and HCV-K2a were examined, and the mutation
      was defined when changes of amino acids in sites specific to different reported
      genotypes were revealed. The mutations were observed in 6/19 (32%) in genotype 1b
      and 9/14 (64%) in 2a. In the 1b group, complete response (CR) was achieved in 5/6
      of the mutant and in 2/13 of the wild type groups (P < 0.05). No relationship was
      observed between IFN effectiveness and HCV-RNA titre in the 1b wild type group.
      In the 2a group, CR was achieved in 4/9 of the mutant and in 4/5 of the wild type
      groups. An inverse relationship between IFN responsiveness and HCV-RNA titre was
      apparent in 1b mutant, 2a wild and 2a mutant. CONCLUSIONS: These data suggest the
      possible relationship between changes in the HCV-NS5B gene and the effect of IFN
      therapy in CHC patients with genotype 1b.

PMID- 10207785
TI  - Minimal role of GB virus-C/hepatitis G virus in fulminant and subfulminant
      hepatitis in Taiwan.
AB  - BACKGROUND: The role of GB virus-C/hepatitis G virus (GBV-C/HGV) in fulminant
      hepatitis (FH) and subfulminant hepatitis (SFH) remains unclear. METHODS: Thirty
      two FH or SFH patients, with adequate clinical information and serum specimens,
      were studied. Serum samples were tested for hepatitis markers and genomes of
      hepatitis A-E viruses, as well as GBV-C/HGV. RESULTS: Of the cases of FH/SFH
      studied, one (3%) was caused by anti-tuberculosis agents, 26 (81%) had
      hepatotropic virus infection, and five (16%) had no identifiable cause. Of the 26
      patients with hepatotropic virus infection, five had acute hepatitis B infection
      (one with acute hepatitis D virus (HDV) co-infection), one had acute hepatitis C
      infection, 16 were hepatitis B surface antigen carriers with reactivation or
      superimposed by unidentified agent(s) (two had triple virus infections), three
      were hepatitis B carriers with HDV superinfection, and one had GBV-C/HGV
      infection in addition to exposure to halothane. GBV-C/HGV-RNA was detected in
      only three of 32 patients (9%) and all had a history of blood transfusion or co
      existing causative factors. Of the 26 patients with hepatotropic virus infection,
      18 were tested for antibodies against GBV-C/HGV envelope protein and seven were
      reactive, suggesting past infection. CONCLUSIONS: The role of GBV-C/HGV in
      causing FH and SFH is minimal in Taiwan and HBV infection remains the major
      aetiology. These findings also suggest the existence of as yet unrecognized
      agents, responsible for such catastrophic illnesses.

PMID- 10207786
TI  - Prevalence of TT virus before and after blood transfusion in patients with
      chronic liver disease treated surgically for hepatocellular carcinoma.
AB  - BACKGROUND: To examine the prevalence of TT virus (TTV) before and after blood
      transfusion, we retrospectively examined serum samples obtained from 55 patients
      who received blood transfusions before, during and after resection of
      hepatocellular carcinoma. METHODS: TT virus DNA was extracted from serum samples
      and detected by nested polymerase chain reaction. Before transfusion, seven
      (12.7%) were positive for TTV. Patients were transfused whole blood or separated
      blood components (fresh frozen plasma, platelet and/or red blood cells), the
      total amount of transfused fresh frozen plasma ranging from 12 to 271 (median 38)
      units. RESULTS: Seven (14.6%) of the 48 TTV-negative patients became positive for
      TTV-DNA 1 month after transfusion. Only one of the seven patients, who was
      already positive for HCV-RNA, exhibited elevation of alanine aminotransferase.
      Five of the newly infected seven patients become negative for TTV during a 2 year
      follow up. CONCLUSIONS: Our findings suggest that the proportion of patients with
      TTV was relatively high in this sample, and that the prevalence of TTV
      transmission by blood components was also relatively high (14.6%). Although TTV
      persisted for more than 6 months in some patients, infection was not noticeable
      during the course of chronic liver disease.

PMID- 10207787
TI  - Analysis of adhesion molecules in patients with idiopathic portal hypertension.
AB  - BACKGROUND: The aetiology of idiopathic portal hypertension (IPH) is unknown.
      However, some evidence of immunological abnormalities in IPH patients has been
      reported. METHODS: As adhesion molecules are important in the interaction between
      lymphocytes and accessory and target cells, the expression and release of the
      soluble form of vascular cell adhesion molecule-1 (VCAM-1) and intercellular
      adhesion molecule (ICAM-1) were examined in this study. RESULTS: In IPH patients,
      the serum level of soluble VCAM-1 was found to be increased, compared with that
      of healthy subjects, fatty liver patients and chronic hepatitis patients. The
      level of soluble ICAM-1 of IPH patients was found to be slightly increased,
      compared with that of healthy subjects; however, it was not different from the
      level in patients with other diseases. The expression of VCAM-1 was observed in
      the sinusoidal lining cells and endothelial cells around the liver vessels of
      several IPH patients. In contrast, ICAM-1 was weakly expressed in sinusoidal
      lining cells and hepatocytes in the liver tissue of only one of four IPH
      patients. CONCLUSIONS: This differential pattern of VCAM-1 and ICAM-1 was found
      in IPH patients and it was suggested that VCAM-1 might be an important molecule
      in the occurrence of IPH.

PMID- 10207788
TI  - Effect of anaemia on haemodynamics in patients with cirrhosis.
AB  - BACKGROUND: It has been suggested that increased blood haemoglobin attenuates
      splanchnic vasodilatation in portal-hypertensive rats by nitric oxide
      inactivation. However, the haemodynamic effect of anaemia in cirrhotic patients
      of varying severity has been rarely discussed. The aim of this study was to
      evaluate the influence of anaemia on systemic and splanchnic haemodynamics in
      cirrhotic patients of differing severity. METHODS: Two hundred and twenty-five
      cirrhotic patients were included in this study. All biochemical and haemodynamic
      results were utilized for analysis. Anaemia was defined as a haemoglobin level
      below the cut-off value of 12 g/dL, which might best predict low systemic
      vascular resistance. RESULTS: Compared with non-anaemic patients, anaemic
      patients had decreased mean arterial pressure (90 +/- 1 vs 95 +/- 1 mmHg, P =
      0.002), and decreased systemic vascular resistance (1022 +/- 25 vs 1227 +/- 30, P
      < 0.0001), and increased cardiac index (4.3 +/- 0.1 vs 3.8 +/- 0.1 L/min per m2,
      P < 0.0001) and increased hepatic venous pressure gradient (16.7 +/- 0.5 vs 14.4
      +/- 0.6 mmHg, P = 0.006). Haemoglobin concentration exerted an influence on the
      degree of vasodilatation in cirrhotic patients, with Child-Pugh's A class (but
      not in Child-Pugh's B and C classes), and in patients without ascites (but not in
      patients with ascites). CONCLUSIONS: It was concluded that anaemia has a negative
      effect on hyperdynamic circulation in patients with early cirrhosis which is not
      observed in patients with advanced cirrhosis.

PMID- 10207789
TI  - Protective role of adrenal glucocorticoids for gastric mucosa in spontaneously
      hypertensive rats.
AB  - BACKGROUND: Spontaneously hypertensive rats (SHR) are a representative animal
      model for disturbance of the pituitary-adrenal axis, as well as disturbance of
      the autonomic nervous system. METHODS AND RESULTS: In this study, we showed that
      adrenalectomy in SHR-induced spontaneous gastric ulcer formation. We further
      investigated how abnormal adrenal secretion is related to the attenuation of
      gastric ulcerogenesis, in terms of leucocyte infiltration and nitric oxide (NO)
      formation. Bilateral adrenalectomy, as well as a sham-operation, were carried out
      at 12 weeks in hypertensive SHR and Wistar-Kyoto rats (WKY) and observations were
      made three weeks later. The number of myeloperoxidase (MPO) positive cells, NADPH
      diaphorase histochemistry and NO synthase (NOS) activity were determined in
      gastric specimens. Only in adrenalectomized, but not sham-operated SHR, WKY and
      adrenalectomized WKY, could gastric ulcers be observed. Although the number of
      cells positive for MPO was significantly lower in hypertensive SHR than those in
      WKY, such cells were increased after adrenalectomy in SHR. In contrast,
      adrenalectomized WKY developed no increase in MPO-positive numbers. The number of
      NADPH diaphorase-positive cells increased after adrenalectomy in both strains,
      the extent of which was much greater in SHR than in WKY. Although NOS activity in
      SHR was lower than that in WKY, it was significantly increased after
      adrenalectomy. CONCLUSIONS: Our data show that the development of a significant
      gastric ulceration may be associated with entrapment of activated leucocytes in
      the gastric mucosa, as well as with an excessive production of NO in
      adrenalectomized SHR. An enhanced adrenal glucocorticoid may be a key factor for
      protecting the gastric mucosa in SHR.

PMID- 10207790
TI  - Anorectal physiology and transit in patients with disorders of thyroid
      metabolism.
AB  - BACKGROUND: Data on anorectal physiology in patients with disordered thyroid
      metabolism are lacking. This prospective study was performed to evaluate
      anorectal physiology in patients with either hyperthyroidism and diarrhoea, or
      hypothyroidism and constipation in order to assess slow transit in hypothyroid
      patients. METHODS: Thirty patients with hypothyroidism and constipation (24
      females, median age 59 years, range 23-80) and 20 patients with hyperthyroidism
      and diarrhoea (12 females, median age 46 years, range 36-62) were evaluated by
      anal manometry, rectal balloon sensation and whole-gut transit markers. Data were
      compared with anorectal physiology and whole-gut transit in 22 healthy controls
      (13 females, median age 51 years, range 24-65). RESULTS: In the hypothyroid
      patients, maximum resting pressure (MRP) and maximum squeeze pressure (MSP) were
      similar to controls (patients, median MRP 55 mmHg (18-98); controls, median MRP
      41 mmHg (20-105) and patients, median MSP 83 mmHg (39-400); controls, median MSP
      88 mmHg (30-230); P > 0.05 for both resting and squeeze pressures). In
      hyperthyroid patients, median MRP and MSP were significantly lower than controls
      (patients, MRP 33 mmHg (8-69); controls MRP 41 mmHg (20-105) P = 0.04 and
      patients, MSP 60 mmHg (26-104); controls, MSP 88 mmHg (30-230); P = 0.03).
      Threshold sensation for impending evacuation in hypothyroid patients was
      significantly higher than controls, while in hyperthyroid patients, threshold
      sensation was significantly lower compared with controls. Maximum tolerable
      rectal volumes in hypothyroid patients was significantly lower compared with
      controls, while no significant difference was found between maximum tolerable
      rectal volumes in hyperthyroid patients and controls. Prevalence of delayed whole
      gut transit in both hypothyroid and hyperthyroid patients was similar to
      controls. Furthermore, 33% of hypothyroid patients and 40% of hyperthyroid
      patients experienced symptoms of bowel dysfunction prior to the onset of their
      thyroid disorder. CONCLUSIONS: Patients with altered thyroid function and bowel
      dysfunction demonstrated abnormalities of anal manometry and rectal sensation.

PMID- 10207791
TI  - Role of bile salt hydrophobicity in distribution of phospholipid species to
      carriers in supersaturated model bile solutions.
AB  - BACKGROUND: Phospholipid species modulate cholesterol-holding capacity and,
      therefore, regulate bile metastability. METHODS: In this study, we investigated
      the effect of bile salt hydrophobicity on the distribution of phospholipids among
      lipid particles in supersaturated model bile solutions (total lipid
      concentration, 9 g/dL; taurocholate/phospholipid ratio 3.0, cholesterol
      saturation index 1.3), by using gel permeation chromatography. RESULTS: With an
      increase of bile salt hydrophobicity in the elution buffer, the uptake of
      cholesterol and phospholipids into bile salt micelles was increased, associated
      with an increased cholesterol/phospholipid molar ratio of the vesicles. In
      contrast, there was an inverse correlation between the hydrophobicity of the
      phospholipid species in the vesicles and that of bile salts in the elution
      buffer, suggesting that hydrophobic bile salts induced preferential uptake of
      hydrophobic phospholipids into bile salt micelles, while less hydrophobic
      phospholipids, with a relatively low cholesterol-holding capacity, remained in
      the vesicles. CONCLUSIONS: These data indicate that bile salt hydrophobicity
      regulates vesicular cholesterol metastability by modulating the hydrophobicity of
      phospholipids in vesicles, as well as the lipid distribution among various
      biliary lipid particles.

PMID- 10207792
TI  - Gastrointestinal: fundic gland polyps.

PMID- 10207793
TI  - Hepatobiliary and pancreatic: a man with right upper quadrant pain and fever.

PMID- 10207795
TI  - Long-term follow-up of a randomized trial of interferon therapy for chronic
      hepatitis B in a predominantly homosexual male population.
AB  - BACKGROUND/AIMS: Extended follow-up of a previously published therapeutic trial
      with interferon alfa is now available to further clarify the long-term outcome of
      HIV-negative and HIV-positive subjects with chronic hepatitis B virus infection
      after interferon alfa therapy. METHODS: Forty-five subjects with compensated
      liver disease and chronic hepatitis B infection with evidence of active hepatitis
      B replication were studied. These subjects were enrolled between 1986 and 1991
      and had been randomized, stratified by HIV status, to either receive interferon
      therapy (10 MU/m2 of lymphoblastoid interferon alfa 3 times per week for 12
      weeks) or no treatment. Hepatitis B serology, serum hepatitis B viral DNA and
      alanine aminotransferase were measured on an annual to biannual basis. CD4
      positive T lymphocyte counts and HIV RNA concentration were also obtained.
      RESULTS: From 9 months post-interferon alfa treatment to the end of the extended
      follow-up (4 to 9 years), the relative risk of seroconverting to anti-HBe
      positive for subjects who had received interferon alfa therapy compared to those
      who did not was not significant in either HIV-negative (p = 0.80) or HIV-positive
      (p = 0.62) subjects. CONCLUSIONS: Unlike the first 9 months following interferon
      alfa therapy, the rate of elimination of markers of hepatitis B virus
      replication, regardless of HIV status, was not increased above the natural rate
      beyond 9 months following interferon alfa therapy.

PMID- 10207796
TI  - Intrafamilial transmission of hepatitis delta virus: molecular evidence.
AB  - BACKGROUND/AIMS: Epidemiologic studies have suggested that transmission of
      hepatitis delta virus (HDV) occurs by intrafamilial routes in some populations in
      southern Italy, where HDV infection is endemic. To further evaluate intrafamilial
      transmission of HDV, we obtained the partial sequence of the viral genome from
      HDV-RNA positive members of families in which two or more immediate family
      members were positive for HDV-RNA. METHODS: The region analyzed was the semi
      conserved region from nucleotides 908 to 1265. Sequences obtained from family
      members were compared with those obtained from a control group of 20 unrelated
      patients. RESULTS: The mean genetic divergence among HDV isolates was 2.8 +/-
      1.7% within the 9 families analyzed, and 7.6 +/- 2.2% among the control group of
      unrelated individuals (p < 0.0001). A Receiver Operating Characteristic curve and
      Youden Index were used to define a cut-off value of 3.5% to discriminate sequence
      variations calculated within families and in the control group. CONCLUSIONS: The
      data indicate that in most family units, HDV-infected members harbored nearly
      identical strains of HDV, and provide molecular support that HDV infection can be
      transmitted within the family. Such spreading among family members highlights the
      role of inapparent transmission through personal contacts.

PMID- 10207797
TI  - Hepatotropism of GB virus C (GBV-C): GBV-C replication in human hepatocytes and
      cells of human hepatoma cell lines.
AB  - BACKGROUND/AIMS: Recently, GB virus C (GBV-C) has been identified as another
      virus potentially causing viral hepatitis. However, its hepatotropism and pattern
      of infection in humans is still unknown. To elucidate the presence and
      replication of GBV-C in the human liver, we investigated tissue samples of six
      explanted livers from five GBV-C mono- or GBV-C/HCV co-infected patients for GBV
      C RNA plus- and minus-strand RNA. METHODS: These tissues were examined using
      nested RT-PCR followed by Southern blot hybridization as well as fluorescence in
      situ hybridization on liver cryosections. To further substantiate susceptibility
      of liver cells for GBV-C, in vitro infection of human hepatoma cells (HuH7,
      HepG2) with GBV-C mono-infected serum was performed. RESULTS: By reverse
      transcription followed by nested PCR (RT-PCR), 5 of 6 liver specimens (4/5
      patients) were positive for GBV-C plus-strand RNA, and viral minus-strand RNA
      could be detected in 4 of 6 liver specimens (4/5 patients). One liver sample was
      negative for GBV-C RNA. In two specimens we could identify GBV-C infection by in
      situ hybridization. Virus infection appeared to be restricted to hepatocytes and
      detection of minus-strand RNA showed viral replication in a few highly infected
      liver cells. In vitro infection of HepG2 or HuH7 cells confirmed these findings
      by a release of virions into supernatant. CONCLUSION: In conclusion, our results
      establish GBV-C as a hepatotropic virus infecting human cells of hepatic origin
      in vivo and in vitro.

PMID- 10207798
TI  - Guided versus blind liver biopsy for chronic hepatitis C: clinical benefits and
      costs.
AB  - BACKGROUND/AIMS: Our objectives were: (1) to assess the clinical benefits and
      costs of performing ultrasound-guided liver biopsy with an automated needle
      compared to blind biopsy with a conventional Trucut needle in patients with
      chronic hepatitis C; (2) to compare the histological yield of automated needles
      with Trucut needles. METHODS: We prospectively studied 166 patients with
      hepatitis C virus who underwent either ultrasound-guided biopsy using automated
      ASAP needles or blind biopsy using conventional Trucut needles. Both groups were
      matched for age, sex, cirrhosis, needle gauge and operator experience. Patient
      tolerance, complications and histological adequacy were assessed. In a separate
      in vitro study, we assessed the histological adequacy of liver biopsy specimens
      obtained using automated and Trucut needles from 10 fresh autopsy cases. RESULTS:
      Ultrasound-guided biopsy caused significantly less biopsy pain (36.4% vs. 47.3%;
      p < 0.0001) and significantly less pain-related morbidity (1.8% vs. 7.7%, p <
      0.05). Although, there was no significant difference in diagnostic yield between
      guided and blind biopsy (98% vs. 94%, p = 0.15), 3 blind biopsies (3.3%),
      including 2 which yielded extra-hepatic tissue, had to be repeated. The
      additional expense of performing guided liver biopsy with automated needles was
      42 Irish Pounds per patient. In vitro, automated ASAP 15G needles provided liver
      specimens comparable to Trucut 15G needles and had the highest histopathologic
      score among the automated needles assessed. CONCLUSIONS: Even in the absence of
      major complications, ultrasound-guided liver biopsy with an automated needle in
      HCV patients is safer, more comfortable and only marginally more expensive than
      blind Trucut biopsy.

PMID- 10207799
TI  - A genotypic study of 217 unrelated probands diagnosed as "genetic
      hemochromatosis" on "classical" phenotypic criteria.
AB  - BACKGROUND/AIMS: The HFE gene is a crucial candidate gene for hemochromatosis.
      The aims of this study were to assess the HFE genotypic profile in a large series
      of unrelated probands diagnosed as having phenotypic hemochromatosis, to
      characterize the sub-group of patients who were not homozygous for the major
      C282Y mutation, and to report the iron status of the detected HFE-identical
      siblings. METHODS: In 217 patients, the phenotypic diagnosis of hemochromatosis
      was based on strict bioclinical and/or histological criteria, and their genotypic
      profile (C282Y and H63D mutations) was determined. RESULTS: 1) 209 of the 217
      probands were C282Y +/+. In 33 cases, an HFE-identical sibling was identified.
      Two of them had neither a clinical nor a biochemical phenotypic profile of
      hemochromatosis in the absence of any external factor which might have attenuated
      this expression. 2) Eight patients (seven males) were not C282Y +/+. Their
      genotypic profiles were: (C282Y +/-): six cases (four were H63D +/- and two H63D 
      /-); (C282Y -/-): two cases (one was H63D +/+, one H63D +/-). Phenotypic
      expression consisted of six cases of mild liver siderosis (among whom were the
      four compound heterozygotes and one case of alcoholic cirrhosis) and two severe
      cases of hepatic iron overload (one with alcoholic cirrhosis). Three HFE
      identical siblings were identified, none of them presenting with iron excess.
      CONCLUSIONS: In our population: 1) The classical phenotypic criteria fitted, in
      96.3% of cases, with a homogeneous genotypic entity defined by homozygosity for
      the C282Y mutation. Incomplete penetrance of the homozygous status was shown by
      the absence of the hemochromatosis phenotypic profile in 6% of the HFE-identical
      siblings. 2) A minority (3.7%) were not homozygous for C282Y. These were
      essentially men with mild iron overload, and might present with distinct iron
      overload entity(ies) as suggested by the presence in three of an HFE-identical
      sibling with absence of iron overload.

PMID- 10207800
TI  - Development of eosinophil peroxidase activity and concomitant alteration of the
      antioxidant defenses in the liver of mice infected with Schistosoma mansoni.
AB  - BACKGROUND/AIMS: The tropical parasite Schistosoma mansoni causes granulomatous
      inflammation following lodging of eggs in portal capillaries. In vitro studies
      indicated that the host reaction should involve reactive oxygen intermediates;
      however, it is not known what occurs in vivo at the site of the disease.
      Moreover, the ultimate pathophysiological effects of oxidative processes depend
      upon antioxidant factors, which are investigated in this study. METHODS: We
      explored the changes in the major enzyme activities involved in liver redox
      metabolism during the course of infection and, for some of them, the mRNA
      expression. We also measured the reduced glutathione and lipid peroxide levels in
      the liver. RESULTS: We found that the deposition of parasite eggs triggers the
      release of endogenous eosinophil peroxidase; enzyme activity developed in the
      immediate vicinity of the eggs and it increased dramatically with time. However,
      Cu,Zn-superoxide dismutase, catalase and glutathione peroxidase activities
      decreased drastically. In contrast, glutathione transferase was unaffected. There
      was no proportional decrease in mRNA levels for the H2O2 scavenging enzymes.
      Reduced glutathione concentrations also dropped as a result of infection. Lastly,
      a two-fold increase in the levels of hepatic products generated by lipid
      peroxidation was observed. CONCLUSIONS: These results show that on the one hand
      oxidative processes occurred at the site of granulomatous inflammation and on the
      other hand the antioxidant capacity of the liver decreased, leading to the
      generation of lipid peroxides. The resulting imbalance between pro- and anti
      oxidant processes may play a central role in the pathology associated with
      schistosomiasis.

PMID- 10207801
TI  - Association of a decrease in antithrombin III activity with a perinatal elevation
      in aspartate aminotransferase in women with twin pregnancies: relevance to the
      HELLP syndrome.
AB  - BACKGROUND/AIMS: Decreased antithrombin III (AT-III) activity and/or
      thrombocytopenia associated with an elevated serum level of aspartate
      aminotransferase in late pregnancy can threaten the lives of both the mother and
      the fetus. We investigated whether antenatal declines in AT-III activity and the
      platelet count occur in late twin pregnancy and whether reduced AT-III activity
      and/or thrombocytopenia precedes an increase in the serum level of aspartate
      aminotransferase. METHODS: The platelet count, AT-III activity, and the serum
      level of aspartate aminotransferase were determined weekly or biweekly in 237
      women with twin pregnancies in a longitudinal and partly prospective study.
      RESULTS: Both AT-III activity and the platelet count decreased gradually in the
      last month of pregnancy, irrespective of the presence or absence of clinical
      signs of pre-eclampsia. A perinatal elevation in aspartate aminotransferase
      occurred in 36 (15%) of 237 women. The risk of a perinatal elevation in aspartate
      amino-transferase increased as the antenatal AT-III activity and/or the platelet
      count decreased. Pre-eclampsia developed in 60 women (25%). The relative risk of
      a perinatal aspartate aminotransferase elevation (95% confidence interval) for
      the 60 women with pre-eclampsia, the 60 women with a platelet count < or = the
      25th percentile (164 x 10(9)/1), and the 60 women with AT-III activity < or = the
      25th percentile (76% of normal) was 1.9 (1.0 to 3.4), 4.1 (2.3 to 7.5), and 5.9
      (3.2 to 11.1), respectively, compared with the remaining 177 women. CONCLUSIONS:
      AT-III activity and platelet count gradually decreased in the last month of twin
      pregnancies. A perinatal aspartate aminotransferase elevation was preceded by
      marked decreases in these parameters in women with twin pregnancies. The
      monitoring of AT-III activity and platelet count in women who exhibit a gradual
      decline in these parameters may help to avoid the development of severe HELLP
      syndrome.

PMID- 10207802
TI  - Transformation-dependent calcium influx by voltage-operated calcium channels in
      stellate cells of rat liver.
AB  - BACKGROUND/AIMS: The transformation of hepatic stellate cells into myofibroblasts
      is a key step in the pathogenesis of fibrotic liver diseases. The intracellular
      signaling associated with hepatic stellate cell transformation becomes a point of
      interest, especially the role of cytosolic free calcium concentration ([Ca2+]i).
      The aim of the study was to investigate possible differences between various
      transformation phenotypes of hepatic stellate cells with regard to the calcium
      influx mediated by L-type voltage-operated calcium channels (L-type VOC).
      METHODS: Hepatic stellate cells were isolated from rat liver by pronase
      collagenase reperfusion and cultured under standard conditions. The
      transformation of hepatic stellate cells was stimulated by treatment with
      transforming growth factor-beta (TGF-beta) or inhibited with interferon-gamma
      (IFN-gamma) and characterized by immunocytochemistry for smooth muscle alpha
      actin and determination of hyaluronan in the culture media with a ligand binding
      assay. [Ca2+]i was measured in individual cells with fluorescence microscopy
      using fura-2. VOCs were activated by the standard procedure of extracellular
      potassium elevation, to achieve depolarization, and identified by various
      controls. RESULTS: In transformed myofibroblasts the activation of VOCs by
      potassium elevation from 5.4 mmol/l to 50.4 mmol/l led to a 19% increase in
      [Ca2+]i in contrast to 0.2% in hepatic stellate cells cultured for 3 days. In 7
      day old hepatic stellate cells, after stimulation of cell transformation with TGF
      beta-1, an enhanced [Ca2+]i response to potassium elevation was detected, while
      inhibition of transformation with IFN-gamma for the same time caused a decreased
      calcium signal compared with untreated control cultures. Short-term treatment
      with the cytokines (1 day) did not influence depolarization-dependent calcium
      signals. CONCLUSION: The results show the [Ca2+]i increase via L-type VOCs to be
      dependent on the transformation level of hepatic stellate cells into
      myofibroblasts which can be influenced by the long-term treatment of hepatic
      stellate cells with TGF-beta or IFN-gamma. In contrast, there is no evidence for
      direct regulation of VOC activity by TGF-beta or IFN-gamma after short-term
      exposure.

PMID- 10207803
TI  - Effect of pentoxifylline on early proliferation and phenotypic modulation of
      fibrogenic cells in two rat models of liver fibrosis and on cultured hepatic
      stellate cells.
AB  - BACKGROUND/AIMS: During liver fibrosis, different fibroblastic cells, i.e.
      hepatic stellate cells (HSCs) or portal fibroblasts, are involved in the
      development of lesions, and acquire myofibroblastic differentiation. We
      investigated, in the rat, whether pentoxifylline can influence the early phase of
      fibrogenesis in two animal models of fibrosis induced by either carbon
      tetrachloride (CCl4) plus acetone (given twice) or bile duct ligation. METHODS:
      The fibroproliferative response and myofibroblastic phenotypic modulation were
      evaluated by PCNA and alpha-smooth muscle (alpha-SM) actin immunohistochemistry,
      respectively, in livers taken 24 h after the last CCl4 treatment or 72 h after
      bile duct ligation. Desmin expression was also measured, and inflammation was
      evaluated by ED-1 staining. Furthermore, proliferation and alpha-SM actin
      expression were studied in cultured HSCs after pentoxifylline treatment. RESULTS:
      In the CCl4-acetone groups, pretreatment with pentoxifylline decreased the
      proliferative response and expression of alpha-SM actin in the HSCs. Similarly,
      pentoxifylline reduced the proliferation and myofibroblastic differentiation of
      portal fibroblasts after bile duct ligation. Pentoxifylline reduced ED-1
      expression, particularly in the CCl4 model, where there was significant
      inflammation. In cultured pentoxifylline-treated HSCs, both proliferation and
      alpha-SM actin expression were decreased. CONCLUSIONS: In both animal models of
      fibrosis, during the early stages of tissue injury, pentoxifylline was able to
      reduce fibroproliferation and myofibroblastic differentiation and to reduce
      hepatocellular damage and the inflammatory response, particularly in the toxin
      induced model. In culture, alpha-SM actin expression decreased in both growing
      and quiescent HSCs treated with pentoxifylline, indicating that the drug may also
      exert a direct effect on hepatic fibrogenic cells.

PMID- 10207804
TI  - Cardiovascular and renal function in normotensive and hypertensive patients with
      compensated cirrhosis: effects of posture.
AB  - BACKGROUND/AIMS: The aim of this study was to evaluate cardiovascular and renal
      function in patients with compensated cirrhosis and essential hypertension in the
      supine position and in response to standing up. METHODS: Twenty-four patients
      with compensated cirrhosis (12 with elevated arterial pressure) and 20 healthy
      volunteers underwent echocardiographic evaluation of left ventricular end
      diastolic and stroke volumes, ejection fraction, cardiac index, arterial
      pressure, peripheral resistance, creatinine clearance and sodium excretion in
      both the supine and the standing position. RESULTS: When supine, only
      normotensive patients had a hyperdynamic circulation, with increased left
      ventricular end-diastolic and stroke volumes, cardiac index, and ejection
      fraction, and reduced peripheral resistance. Creatinine clearance and sodium
      excretion were comparable in patients and controls. Standing induced a decrease
      in end-diastolic volume in all subjects. Healthy volunteers maintained
      cardiovascular homeostasis by increasing ejection fraction and heart rate, while
      both normotensive and hypertensive cirrhotic patients experienced a fall in
      stroke volume and cardiac index, despite a marked activation of the renin
      aldosterone and sympathetic nervous system. Creatinine clearance decreased only
      in normotensive patients, who experienced the greatest reduction in sodium
      excretion. CONCLUSIONS: Compensated cirrhotic patients with arterial hypertension
      had no evidence of hyperdynamic circulation. Like their normotensive
      counterparts, hypertensive patients had an impaired cardiovascular response to
      the postural challenge, but a lesser degree of renal dysfunction during standing.

PMID- 10207806
TI  - Myofibroblasts in the cirrhotic rat liver reflect hepatic remodeling and
      correlate with fibrosis and sinusoidal capillarization.
AB  - BACKGROUND/AIMS: Myofibroblasts are essential in fibrogenesis during development
      of cirrhosis. In the present study we stereologically quantitated MFB's and
      correlated them with fibrosis and sinusoidal capillarization. METHODS: Male SD
      rats were rendered cirrhotic by chronic exposure to phenobarbital/CCl4, (CIR; n =
      16); untreated littermates served as controls (CTR; n = 10). Sinusoidal
      capillarization was assessed by a multiple indicator dilution technique as
      previously described. The volume fractions of myofibroblasts and other liver
      components were estimated by morphometry. RESULTS: Myofibroblasts averaged 15.7
      +/- SD 0.7% in CIR as compared to 6.7% +/- SD 0.4% in CTR (p < 0.01). An extra
      littoral compartment of myofibroblasts was found in portal tracts and within
      fibrous septa. In CIR, hepatocytes showed a bimodal distribution of volume
      fractions, and hepatocyte volume distribution disclosed a mirror image of that of
      myofibroblasts. Connective tissue was markedly increased in CIR, averaging 13.2
      +/- 1.2% in CIR vs. 1.2 +/- 0.3% in CTR (p < 0.0001). Extravascular albumin space
      -a measure of sinusoidal capillarization--was reduced by 44% in CIR (0.028 +/-
      0.017 vs. 0.050 +/- 0.010 ml/g; p < 0.001). The volume fraction of myofibroblasts
      correlated best with extravascular albumin space (r = -0.84, p < 0.001). Multiple
      regression analysis selected only extravascular albumin space and connective
      tissue to be determined by the volume fraction of myofibroblasts (r = 0.923; p <
      0.001). CONCLUSION: We conclude that increased myofibroblasts reflect the degree
      of hepatic remodeling rather than cirrhosis inasmuch as myofibroblast volume
      fraction inversely reflects that of hepatocyte bimodality. Myofibroblasts form an
      extra-littoral compartment in this model of CIR and correlate with hepatic
      fibrosis and sinusoidal capillarization.

PMID- 10207805
TI  - Albumin improves the response to diuretics in patients with cirrhosis and
      ascites: results of a randomized, controlled trial.
AB  - BACKGROUND/AIMS: Diuretic treatment of ascites could result in intravascular
      volume depletion, electrolyte imbalance and renal impairment. We investigated
      whether intravascular volume expansion with albumin exert beneficial effects in
      cirrhosis with ascites. METHODS: In protocol 1, 126 cirrhotic inpatients in whom
      ascites was not relieved following bed rest and a low-sodium diet, were randomly
      assigned to receive diuretics (group A) or diuretics plus albumin, 12.5 g/day
      (group B). In protocol 2, group A patients continued to receive diuretics and
      group B diuretics plus albumin (25 g/week) as outpatients and were followed up
      for 3 years. End points were: disappearance of ascites, duration of hospital stay
      (protocol 1), recurrence of ascites, hospital readmission and survival (protocol
      2). RESULTS: The cumulative rate of response to diuretic treatment of ascites was
      higher (p < 0.05) and hospital stay was shorter (20 +/- 1 versus 24 +/- 2 days, p
      < 0.05) in group B than in group A patients. After discharge, group B patients
      had a lower cumulative probability of developing ascites (19%, 56%, 69% versus
      30%, 79% and 82% at 12, 24 and 36 months, p < 0.02) and a lower probability of
      readmission to the hospital (15%, 56%, 69% versus 27%, 74% and 79%, respectively,
      p < 0.02). Survival was similar in the two groups. CONCLUSIONS: Albumin is
      effective in improving the rate of response and preventing recurrence of ascites
      in cirrhotic patients with ascites receiving diuretics. However, the cost/benefit
      ratio was favorable to albumin in protocol 1 but not in protocol 2.

PMID- 10207807
TI  - Interferon therapy lowers the rate of progression to hepatocellular carcinoma in
      chronic hepatitis C but not significantly in an advanced stage: a retrospective
      study in 1148 patients. Viral Hepatitis Therapy Study Group.
AB  - BACKGROUND/AIM: Hepatocellular carcinoma frequently develops during the advanced
      stages of chronic hepatitis C. We examined whether interferon prevents the
      development of hepatocellular carcinoma in chronic hepatitis C patients. METHODS:
      Japanese patients with chronic hepatitis C (n = 1.148; 117 with portal fibrous
      expansion (F1), 636 with bridging fibrosis (F2), 355 with bridging fibrosis and
      architectural distortion (F3)) and 40 cirrhotic (F4) patients were treated with
      interferon. These patients were followed from 1 to 7 years after interferon
      therapy. Blood tests and image analysis were serially performed to assess
      response to interferon and to detect hepatocellular carcinoma. Fifty-five
      cirrhotic type C patients (control F4) not receiving interferon were enrolled in
      this study. RESULTS: Sustained (SR: 27.5%) and transient (TR: 23.0%) responders
      totaled 50.5%, while 49.5% did not respond to interferon. SR showed an
      improvement in disease stage reflected by increased platelet counts. Fifty-two
      patients (9 F2, 36 F3, and 7 F4) developed hepatocellular carcinoma in the follow
      up period; 3 SR, 8 TR, and 41 non-responders (NR). The cumulative incidence of
      hepatocellular carcinoma in F2 was significantly lower (p = 0.019) in SR compared
      with NR, but not in SR in F3 and F4 patients. However, the cumulative incidence
      of hepatocellular carcinoma was significantly decreased in all SR (p = 0.0001)
      and TR (p = 0.0397) compared with all NR. CONCLUSION: These results indicate that
      interferon therapy in chronic hepatitis C patients lowered the rate of
      progression of hepatocellular carcinoma in sensitive cases but not in patients in
      an advanced stage.

PMID- 10207808
TI  - Clinical efficacy of portal vein stent placement in patients with hepatocellular
      carcinoma invading the main portal vein.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma frequently invades the portal veins,
      and when it invades the main portal vein, the patient's prognosis is extremely
      poor. This study was undertaken to evaluate the clinical efficacy of stent
      placement into the portal vein in these patients. METHODS: Twenty-one patients
      with hepatocellular carcinoma invading the main portal vein were studied. Stents
      were placed in the portal veins to compress tumor thrombi after percutaneous
      transhepatic portography. RESULTS: Stents were successfully placed in the portal
      veins in all patients. Portal venous pressure significantly decreased from 25.3
      +/- 7.4 mmHg to 22.4 +/- 6.6 mmHg (p < 0.0001) immediately after stent placement,
      leading to improvement in gastroesophageal varices, melena and ascites. Although
      a pseudoaneurysm of the hepatic artery related to portal vein puncture developed
      in one patient, there were no major complications in the other 20 patients. Blood
      flow through the stent was maintained during the survival period in 15 patients.
      The mean stent patency period was 12.4 months. Fifteen patients underwent
      transcatheter arterial chemoembolization without major complications after stent
      placement. The survival rate was 64.2% at 6 months and 29.2% at 1 and 2 years,
      respectively. The mean survival period was 13.7 months. CONCLUSION: Stent
      placement into the portal vein is a relatively safe and feasible procedure. It
      improves portal hypertension, expands treatment options, and helps to prolong the
      survival period in patients with hepatocellular carcinoma invading the main
      portal vein.

PMID- 10207809
TI  - A 3-year prospective study on serum tumor markers used for detecting
      cholangiocarcinoma in patients with primary sclerosing cholangitis.
AB  - BACKGROUND/AIMS: Patients with primary sclerosing cholangitis (PSC) have an
      increased risk of developing cholangiocarcinoma (CC), which is notoriously
      difficult to diagnose since these patients may have increased levels of bilirubin
      due to benign strictures. To evaluate the validity of different tumor markers as
      an aid to diagnosing CC, we have carried out serial serum tumor marker analyses
      in patients with PSC who have been followed for several years. METHODS: Seventy
      five patients with PSC, without any clinical signs of CC were included in the
      study. They were investigated every 6th months for 3 years, with extensive liver
      function tests and four tumor serum markers CEA, CA 19-9, CA 50 and CA 242. The
      patients were then followed for 5 years to exclude the possibility that CC
      remained unrecognized. RESULTS: Of the 75 patients, two (3%) developed CC during
      the 3-year period. One of these had normal levels, and one had significantly
      increased levels of the tumor markers. In the follow-up part of the study two
      further patients died from CC and one from hepatocellular carcinoma, 3 and 4
      years after the 3-year study, respectively. Twenty-one patients had an increase
      of one of the markers on at least one occasion. Five patients had a transient
      increase of more than double the upper normal limit of the tumor markers on more
      than one occasion. There was a good correlation between CA 19-9, CA 50 and CA
      242, but not with CEA. Fourteen of the 75 patients had periods of increased
      bilirubin levels, but none of these showed increased tumor markers. CONCLUSIONS:
      The serum tumor markers CEA, CA 19-9, CA 50 and CA 242 are of limited value for
      the detection of CC in patients with PSC because of low specificity. However, we
      found no falsely increased values in patients with hyperbilirubinemia.

PMID- 10207810
TI  - Hepatic regeneration in insulin-like growth factor binding protein-1 transgenic
      mice.
AB  - BACKGROUND/AIMS: Partial hepatectomy results in activation of genes in the
      residual liver tissue which serve to restore glucose homeostasis and regenerate
      liver mass. Expression of insulin-like growth factor binding protein-1 (IGFBP-1)
      is up-regulated following partial hepatectomy and IGFBP-1 can modulate both the
      metabolic and mitogenic effects of insulin-like growth factor-1 (IGF-I). The aim
      of the study was to compare the effects of partial hepatectomy on blood glucose
      levels and hepatic regeneration in wild-type and transgenic mice which
      constitutively overexpress IGFBP-1. METHODS: Hepatic IGFBP-1 mRNA, blood glucose
      concentrations, liver mass and hepatic DNA synthesis were compared in sham
      operated and partially hepatectomized transgenic and wild-type mice. RESULTS:
      Hepatic IGFBP-1 mRNA was higher in sham-operated transgenic than wild-type mice,
      but in both groups of mice, partial hepatectomy was associated with a significant
      rise in IGFBP-1 mRNA. The absolute decline in blood glucose levels following
      partial hepatectomy was greater in transgenic mice. Basal DNA synthesis and the
      response to IGF-I in isolated hepatocytes from both groups of mice were similar,
      and DNA synthesis in the regenerating liver in vivo was not significantly
      different in transgenic as compared to wild-type mice: 449.3 +/- 63.9 vs. 321.6
      +/- 52.3 cpm/microgram DNA. Hepatic regeneration as measured by liver weight
      after hepatectomy was not different between transgenic and wild-type mice.
      CONCLUSIONS: Constitutive overexpression of IGFBP-1 does not enhance hepatic
      regeneration and does not prevent the decline in blood glucose following partial
      hepatectomy.

PMID- 10207811
TI  - Development of intraepithelial T lymphocytes in the intestine of irradiated SCID
      mice by adult liver hematopoietic stem cells from normal mice.
AB  - BACKGROUND/AIMS: We recently reported the adult mouse liver to contain c-kit+
      stem cells that can give rise to multilineage leukocytes. This study was designed
      to determine whether or not adult mouse liver stem cells can generate
      intraepithelial T cells in the intestine as well as to examine the possibility
      that adult liver c-kit+ stem cells originate from the fetal liver. METHODS: Adult
      liver mononuclear cells, bone marrow (BM) cells, liver c-kit+ cells or bone BM c
      kit+ cells of BALB/c mice were i.v. transferred into 4 Gy irradiated CB17/-SCID
      mice. In other experiments, fetal liver cells from Ly5.1 C57BL/6 mice and T cell
      depleted adult BM cells from Ly5.2 C57BL/6 mice were simultaneously transferred
      into irradiated C57BL/6 SCID mice (Ly5.2). At 1 to 8 weeks after cell transfer,
      the SCID mice were examined. RESULTS: Not only BM cells and BM c-kit+ cells but
      also liver mononuclear cells and liver c-kit+ cells reconstituted gamma delta T
      cells, CD4+ CD8+ double-positive T cells and CD8 alpha+beta- T cells of
      intestinal intraepithelial lymphocytes of SCID mice. Injection of a mixture of
      fetal liver cells from Ly5.1 C57BL/6 mice and adult BM cells from Ly5.2 C57BL/6
      mice into Ly5.2 C57BL/6 SCID mice induced both Ly5.1 and Ly5.2 T cells, while
      also generating c-kit+ cells of both Ly5.1 and Ly5.2 origins in the liver.
      CONCLUSIONS: Adult mouse liver stem cells were able to generate intestinal
      intraepithelial T cells of the SCID mice, and it is thus suggested that some
      adult liver stem cells may indeed be derived from the fetal liver.

PMID- 10207813
TI  - Auxiliary versus orthotopic liver transplantation for acute liver failure. EURALT
      Study Group. European Auxiliary Liver Transplant Registry.
AB  - BACKGROUND/AIMS/METHODS: We report 1-year results after auxiliary liver
      transplantation for acute liver failure in a cohort of 47 patients transplanted
      in 12 European centers as compared with those of 384 consecutive patients
      undergoing orthotopic liver transplantation for acute liver failure in the
      Eurotransplant area. RESULTS: One-year patient survival resp. retransplant-free
      patient survival did not differ between orthotopic (61%, 232/384 resp. 52%,
      200/384) and auxiliary liver transplantation (62%, 29/47 resp. 53%, 25/47). One
      year patient survival resp. retransplant-free patient survival after auxiliary
      partial orthotopic liver transplantation was 71% (25/35) resp. 60% (21/35), not
      significantly different from orthotopic liver transplantation (61%, 232/384 resp.
      52%, 200/384), while both transplantation techniques had better 1-year patient
      survival resp. retransplant-free patient survival than after heterotopic
      auxiliary liver transplantation (33%, 4/12) (p < 0.05). Primary nonfunction was
      more frequent after heterotopic auxiliary liver transplantation (3/12, 25%) than
      after orthotopic liver transplantation (21/384, 5.5%), while the incidence did
      not differ between orthotopic liver transplantation and auxiliary partial
      orthotopic liver transplantation (3/35, 8.5%). Portal vein thrombosis was more
      frequent after both heterotopic auxiliary liver transplantation (5/12, 42%) and
      auxiliary partial orthotopic liver transplantation (5/35, 14%) than after
      orthotopic liver transplantation (2/384, 0.5%) (p < 0.001). Of the patients, 65%
      (17/26) surviving auxiliary liver transplantation for 1 year without
      retransplantation by orthotopic liver transplantation were free of
      immunosuppression within 1 year, compared with none of the patients transplanted
      by orthotopic liver transplantation (p < 0.01). CONCLUSIONS: Auxiliary liver
      transplantation, especially auxiliary partial orthotopic liver transplantation,
      offers an advantage over orthotopic liver transplantation in acute liver failure
      in terms of a chance of a life free of immunosuppression, apparently without
      jeopardizing chances of survival. Reduction of the incidence of primary
      nonfunction and vascular complications should be a focus of research in auxiliary
      liver transplantation. These findings need to be confirmed in a prospective
      study.

PMID- 10207812
TI  - Dietary iron overload inhibits carbon tetrachloride-induced promotion in chemical
      hepatocarcinogenesis: effects on cell proliferation, apoptosis, and
      antioxidation.
AB  - BACKGROUND/AIMS: The aim of this study was to investigate if feeding with
      carbonyl iron would facilitate the development of preneoplastic lesions initiated
      by diethylnitrosamine (DEN) and promoted by CCl4-induced liver cirrhosis.
      METHODS: Male Wistar rats were fed a diet with 1.25%-2.5% carbonyl iron for 23
      weeks and received intragastric injections of CCl4 (1.0 or 2.0 ml/kg per week)
      for 13 weeks, followed by one i.p. injection of DEN (200 mg/kg), after which CCl4
      was administered for 8 additional weeks. Animals were killed 48 h after the first
      CCl4 injection to evaluate liver necrosis, 8 weeks later to evaluate fibrosis,
      and 9 weeks after DEN to determine formation of glutathione S-transferase 7,7
      (GST-7,7) positive foci. RESULTS: Treatment with iron counteracted the increased
      serum alanine aminotransferase levels and liver necrosis following CCl4
      administration. Hepatic levels of reduced Q9 and alpha-tocopherol were elevated
      in rats treated with CCl4 and decreased in rats treated with iron compared to the
      controls. Fibrogenesis was not altered by iron treatment. Nine weeks after DEN
      initiation, the number and volume density of GST-7,7-positive foci in rats
      treated with CCl4 were significantly increased as compared with controls, but co
      treatment with iron inhibited this increase. Apoptotic index was increased in
      iron-loaded livers, and labelling index (the fraction of S-phase hepatocytes) was
      decreased by co-treatment with iron in livers exposed to CCl4. CONCLUSION:
      Carbonyl iron depleted hepatic levels of antioxidants, it decreased CCl4-induced
      necrosis and cell proliferation, it enhanced apoptosis and did not facilitate
      fibrogenesis. These effects together may explain the suppression of CCl4-induced
      promotion after DEN initiation exerted by carbonyl iron in the present study.

PMID- 10207814
TI  - Liver transplantation and HBsAg-positive postnecrotic cirrhosis: adequate
      immunoprophylaxis and delta virus co-infection as the significant determinants of
      long-term prognosis.
AB  - BACKGROUND/AIMS: The place of liver transplantation in hepatitis B viral (HBV)
      related diseases remains controversial because of the high rate of reinfection.
      The aim of this study was to define the determinants of long-term prognosis after
      transplantation. METHODS: Fifty-eight patients were transplanted during the
      period February 1984-September 1996. Six patients died during the early (< 3
      months) posttransplant period from causes unrelated to HBV infection. All 52 long
      term (> 3 months) survivors were evaluated in relation to the mode of
      presentation, viral replication at time of transplantation, absence of
      hepatocellular cancer at time of transplantation and use of adequate
      immunoprophylaxis (IP). Adequate immunoprophylaxis, defined as maintenance of
      anti-HBs levels over 100 mUI/ml, was introduced in December 1989. Intention-to
      treat IP analysis compared patients transplanted before and after this date. The
      median follow-up was 74 months (range 4 to 131). Forty-seven patients (90%) had a
      minimal follow-up of 3 years. RESULTS: Five-year actuarial survival rates of 58
      patients and of 52 long-term survivors were 72 +/- 6% and 80 +/- 6%,
      respectively. Univariate analysis showed that delta co-infection (n = 25)
      significantly improved survival (p < 0.001) [96 +/- 4% vs 63 +/- 10% in HBV
      patients (n = 27) at 5 years] as did absence of hepatocellular cancer (n = 36) (p
      = 0.020) [89 +/- 5% vs 61 +/- 12% in 16 non-cancer patients]. IP, however,
      significantly influenced 5-year survival in the HBV-patient group (n = 17) (p =
      0.001) [85 +/- 10% vs 30 +/- 14% in 10 patients without IP). Multivariate
      analysis selected delta co-infection (p = 0.002) and IP (p = 0.01) as the
      significant determinants of prognosis independently influencing survival. Uni-
      and multivariate analyses showed that survival without reinfection was
      significantly influenced by IP (p = 0.002) [73 +/- 8% (n = 31) versus 33 +/- 12%
      in 15 non-treated patients). CONCLUSIONS: Delta virus co-infection and
      immunoprophylaxis are the most important prognostic factors after transplantation
      for postnecrotic HBsAg-positive cirrhosis. Transplantation can be proposed as a
      therapeutic tool only if life-long adequate adjuvant therapy can be achieved.
      Under this condition good results can even be obtained if there is viral
      replication at the time of transplantation.

PMID- 10207815
TI  - High pre-treatment serum hepatitis B virus titre predicts failure of lamivudine
      prophylaxis and graft re-infection after liver transplantation.
AB  - BACKGROUND/AIMS: Orthotopic liver transplantation has an established role for the
      treatment of patients with chronic liver failure secondary to hepatitis B virus
      (HBV) infection. Unfortunately, recurrent infection of the graft can be
      associated with aggressive disease, and with diminished graft and patient
      survival. Currently, the role of nucleoside analogues for prevention of graft re
      infection is being evaluated. Preliminary results are encouraging, but treatment
      failure has been associated with emergence of drug-resistant virus. METHODS: We
      have studied ten consecutive patients who received lamivudine prophylaxis for
      prevention of HBV graft reinfection. Sequential sera, collected prelamivudine
      then during treatment before and after liver transplantation, were examined.
      Conventional serological markers were measured, as were serum viral DNA levels
      with a sensitive quantitative polymerase chain reaction assay. RESULTS:
      Lamivudine treatment effected a reduction in serum HBV levels, but six patients
      still had measurable viral DNA at the time of transplantation. Five patients
      developed graft re-infection with lamivudine-resistant virus. Resistant virus
      emerged 8 to 15 months post-transplant. The likelihood of emergence of resistant
      virus was related to the pre-treatment serum HBV titre. Persistent serum viral
      DNA positivity and evidence of graft re-infection during the early post
      transplant period did not predict the subsequent emergence of resistant virus.
      CONCLUSIONS: Our observations suggest that the resistant species may be present
      in the viral quasispecies in the serum and liver of patients with high-level
      replication prior to lamivudine exposure. The resistant species can persist
      during lamivudine treatment prior to transplantation, and emerge following
      transplantation. These observations suggest strategies which might prevent the
      emergence of drug-resistant species, and imply that graft re-infection may be a
      preventable phenomenon.

PMID- 10207816
TI  - Triggering of acute alcoholic hepatitis by alpha-interferon therapy.
AB  - BACKGROUND/AIMS: Alcohol may induce autoimmunity by recognition of acetaldehyde
      modified proteins which may be implicated in the pathogenicity of acute alcoholic
      hepatitis. We report here the potential role of alpha-interferon, a potent
      inducer of the autoimmunity process, in inducing alcoholic hepatitis. METHODS: We
      analyzed clinical, biological, virological and histological features in two cases
      where alpha-interferon treatment for HCV-related hepatitis led to a marked
      increase in aminotransferase activities. RESULTS: alpha-interferon as treatment
      of HCV-related hepatitis seemed to exacerbate acute alcoholic hepatitis despite
      moderate alcohol consumption. In Case 1, moderate daily alcohol intake of 40 g
      during therapy led to biopsy-proven acute alcoholic hepatitis, while the same
      consumption before therapy did not. In Case 2, before treatment, the liver biopsy
      showed mild acute alcoholic hepatitis; aminotransferases increased during alpha
      interferon therapy, although no increase in alcohol intake was observed.
      CONCLUSION: alpha-interferon therapy by its immunomodulatory properties could be
      implicated in alteration of the course of acute alcoholic hepatitis. These
      observations emphasize that the decision to treat with alpha-interferon when
      there is even moderate alcohol consumption should be carefully weighted in HCV
      infected patients.

PMID- 10207817
TI  - Images in hepatology. Diffuse liver metastasis mimicking cirrhosis in a patient
      with choroid melanoma.

PMID- 10207818
TI  - Intravenous albumin with diuretics: protean lessons to be learnt?

PMID- 10207819
TI  - The outcome of hepatitis C virus infection after liver transplantation--is it
      influenced by the type of immunosuppression?

PMID- 10207820
TI  - Treatment of alcoholic fatty liver: is the metabolic effect of metadoxine the
      only reason for improved liver function?

PMID- 10207821
TI  - Elevated serum dipeptidyl peptidase IV (CD26, EC 3.4.14.5) activity in patients
      with primary biliary cirrhosis.

PMID- 10207822
TI  - The pattern of sexual politics: feminism, homosexuality and pedophilia.
AB  - Until recently sex and gender issues were thought to be biological or natural
      rather than political. The feminist movement largely changed perceptions of
      gender, and the gay and lesbian movements significantly altered conceptions of
      sex, so that what were once seen as permanent moral standards are now viewed as
      historical and political constructions. As views of these groups have moved
      towards social constructionism, perceptions of child sexuality have become more
      absolutist. Current attitudes towards child sexuality and representations of it
      resemble historical attitudes towards women and homosexuals. This article argues
      that there is a two-phase pattern of sexual politics. The first is a battle to
      prevent the battle, to keep the issue from being seen as political and
      negotiable. Psychological and moral categories are used to justify ridicule and
      preclude any discussions of the issue, and standard Constitutional guarantees are
      seen as irrelevant. The second phase more closely resembles traditional politics
      as different groups argue over rights and privileges. Feminist and gay/lesbian
      politics have recently entered the second phase, while pedophilia is in the
      first.

PMID- 10207823
TI  - Identity in political context: lesbian/gay representation in the public sphere.
AB  - Discourses constructed to represent lesbians and gay men in the public sphere
      generate an essentialist identity which is both necessary and damaging.
      Legislative debate illustrates the production of a constrictive and homogeneous
      identity rejected by many gay/lesbian scholars and activists. Discussion of the
      rhetorical power of identity claims has produced alternative stances toward
      variant sexuality. This discussion can be advanced by challenging dominant
      constructions of civil rights and the public sphere.

PMID- 10207824
TI  - The politics of counter-rejection: gay christians and the church.
AB  - This paper analyzes the accounts constructed by 60 gay male Christians in
      managing the stigma imposed on them by the Church. These accounts signify that
      they, having developed a positive self-image, are involved in the politics of
      counter-rejection of the Church and its official positions on the issue of
      homosexuality. Their counter-rejection of the Church as a moral arbiter is
      predicated on four bases: (1) the Church's ignorance of sex and sexuality, (2)
      the Church's ignorance of all sexualities as God's creation, (3) the Church's
      misinterpretation of biblical passages on homosexuality, and (4) the Church's
      fallibility. Having counter-rejected the Church by challenging its credibility,
      the counter-rejection of the Church's official positions is a matter of course.
      Their experiences highlight the ability of stigmatized social actors to invent
      social biographies not only to defend their moral choices, but also to challenge
      the credibility of sources that question and stigmatize their choices.

PMID- 10207825
TI  - Extent of relational stigmatization of lesbians and their children by
      heterosexual college students.
AB  - Within the judicial and clinical communities, the stigmatization of children with
      lesbian mothers is often seen as inevitable. Even lesbian mothers themselves
      often impose secrecy upon their children based on fears that stigmatization will
      occur. In two studies, college students were asked to indicate how willing they
      would be to enter into relationships with lesbians and their children. Relational
      stigma was greater toward lesbians that their children and acceptance decreased
      as relational closeness increased. However, between 80 and 100 percent of
      students were willing to be acquaintances, friends, or best friends with children
      of lesbians. Although there were no sex differences in acceptance of lesbians,
      women were more willing to engage in relationships with children of lesbians than
      were men. Persons who believed that homosexuality was caused by environmental
      factors were less willing than persons with other beliefs to date or marry the
      child of a lesbian.

PMID- 10207826
TI  - Coming out to parents: perceptions of family relations, perceived resources, and
      identity expression as predictors of identity disclosure for gay and lesbian
      adolescents.
AB  - This paper examines perceptions of family relations, identity expression, and pro
      lesbian/gay resources as factors influencing coming out to parents. One hundred
      seventy-two adolescents responded to a survey originating from a clinical support
      group for lesbian and gay youth. Findings indicate that weak family relations
      significantly detract from coming out to parents indirectly through identity
      expression and perceived resources. Excluding the effects of family relations,
      adolescents perceiving supportive resources and expressing their lesbian/gay
      identity were more likely to come out to parents.

PMID- 10207827
TI  - It's a small world.

PMID- 10207828
TI  - The experience of transition for a daughter caregiver of a stroke survivor.
AB  - The purpose of this study was to describe the experience of transition for a
      daughter caregiver of a stroke survivor. A phenomenologic, longitudinal case
      study of a woman in her late twenties provided the means by which the lived
      experience of transition could be studied and understood. The eleven
      unstructured, audiotaped interviews took place approximately every two weeks over
      a six and a half month period. They began six weeks after her mother's stroke and
      lasted until three months after her mother returned home, when life became more
      organized and predictable for a time. The interviews were transcribed verbatim
      and analyzed according to a modified version of Colaizzi's descriptive
      phenomenologic methodology. Since there was a temporal consideration, a time
      ordered matrix was used to identify themes over time. The themes that emerged
      over time included: (a) changing relationships, (b) becoming a caregiver then
      stepping back, (c) enduring emotional turbulence, (d) taking one day at a time
      and (e) struggling to hang onto hope. Integration of the themes provided an
      exhaustive description. The experience of transition was a process that involved
      disruptions in close relations and daily living. The connection to a network of
      relationships changed to disconnection, and the fabric of interrelated lives
      began to unravel. The many sensations experienced were different and conflicting,
      revealing a rapidly changing perception of the world. An unknown future
      threatened to become overwhelming. Focusing on the present helped to quell the
      turbulent sensations experienced. An unknown future temporarily provided the
      opportunity to hope that daily life could once again become familiar and
      comfortable. The extent and object of hope changed over time. A pattern of chaos
      exemplified the process of transition. The passage of time revealed that life as
      it was known before the transition had changed. A new way of being in the world
      was experienced.

PMID- 10207830
TI  - An algorithm for diagnosis and treatment of status epilepticus in adults.
AB  - Convulsive or generalized tonic-clonic status epilepticus (SE) is a neurological
      emergency that can lead to transient or permanent brain damage or even death. A
      conceptual model was developed to assist nurses and other medical professionals
      to differentiate between convulsive and nonconvulsive SE. An algorithm was then
      designed to aid nursing and medical staff in decision making about the type of SE
      and pharmacological intervention needed to stop prolonged or repetitive seizures
      occurring in patients undergoing video electroencephalogram (EEG) monitoring. A
      treatment algorithm for diagnosing and treating SE has clinical benefits in the
      practice setting of an inpatient comprehensive epilepsy program. Episodes of SE
      are more accurately classified and faster successful treatment of the episode
      occurs.

PMID- 10207829
TI  - The journey to multiple sclerosis: a qualitative study.
AB  - The diagnosis of multiple sclerosis (MS) often creates more questions than
      answers. It is not uncommon to hear about individuals who receive the diagnosis
      with relief and surprise, However, the implications of being diagnosed with a
      chronic illness like MS is complex. There is no known cure for this disease that
      has remissions, relapses and possible continued progression. For individuals
      diagnosed with MS, responding to the physical and psychological stresses of a
      condition with an unknown cause and no cure is challenging. The purpose of this
      study was to explore the individual's experience of having symptoms for a period
      of time and then to be told they have MS. The phenomenological qualitative
      research method was used to illuminate the nature of their experiences. The time
      course spanned before diagnosis, at diagnosis and following diagnosis. Interviews
      were conducted with five purposefully selected participants. The process of data
      analysis highlighted common threads and patterns among informants. Four major
      themes emerged: Whispered Beginnings, Echoes of Silence, The Spoken Words, and
      Recreating Voice. The experiences of individuals recently diagnosed with MS are
      illuminated in order to provide insight and information to health care providers
      who are faced with telling a person the diagnosis of MS.

PMID- 10207831
TI  - Organ donation: the family's right to make an informed choice.
AB  - The need for organ transplants has increased 200% over the past decade, while the
      number of organ donors has remained relatively constant. The family's refusal to
      consent to organ donation has been cited as one of the key factors in the
      shortage of organs. Lack of understanding about brain death and organ donation
      have been identified as reasons for refusal to consent. Families of potential
      organ donors are receiving inadequate information to make informed choices about
      organ donation, and their emotional needs are not consistently met. Neuroscience
      nurses can improve consent rates for organ donation by effectively addressing the
      needs of the potential donor family and offering them the option to donate their
      loved one's organs.

PMID- 10207832
TI  - The use and effectiveness of alternative therapies in multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic debilitating disease with no cure. There has
      been increasing interest in the use of alternative therapies in combination with
      or in place of traditional therapies. Nurses and other health care professionals
      must become more aware of reasons persons with MS are using alternative therapies
      and identify any risks or potential benefits. The role of the health care
      professional is to educate persons with MS on contemporary research, cost and
      regulation of these therapies.

PMID- 10207833
TI  - A review of pharmacodynamics and pharmacokinetics in seizure management.
AB  - Drug therapy is the most widely effective mode of treatment for epilepsy.
      Knowledge about the mechanisms of action and metabolism for antiepileptic
      medications has grown significantly in the past decade as understanding of
      neurotransmitters and cell physiology has evolved. This knowledge has resulted in
      engineering of new seizure controlling drugs. Understanding the pharmacological
      actions and pharmacokinetics of AEDs assists the advanced practice nurse in
      prescriptive decision-making and all nurses in monitoring patient response to
      therapy. This knowledge can also assist nurses to provide accurate information to
      patients receiving antiepileptic drugs.

PMID- 10207834
TI  - Phagocytosis of new cementum-like islets formed inside the gingival connective
      tissue in cyclosporin-A treated rats.
AB  - Three control and 3 experimental rats were administered vehicle or cyclosporin-A
      solutions. Animals were anaesthetized, tissues fixed and jaws processed for Epon
      inclusion. Histological examination of serially cut areas revealed the presence
      inside the gingival connective tissue of new cementum-like islets (NCLIs)
      associated to or engulfed by voluminous multinucleated cells (MCs). These
      complexes were located adjacent to blood vessels, at 250-350 microns from the
      root surface. Histomorphometric study indicated that the volume of the NCLIs
      varied from 3900 to 72,900 microns 3 and that of the MCs from 822 to 56,190
      microns 3. The latter bore up to 14 nuclear profiles. Comparative evaluation of
      the NCLI-MC associations to other complexes "multinucleated cell(s)-resorbed
      material" seems to indicate that the phagocytosis of the NCLIs is dictated by
      their ectopic location, rather than their nature (new cementum-like structures).
      Therefore the MCs should be considered as foreign body giant multinucleated cells
      rather than cementoclasts.

PMID- 10207835
TI  - In vitro studies of lymphocyte apoptosis induced by the periodontal pathogen
      Porphyromonas gingivalis.
AB  - Apoptosis has a physiological role in lymphocyte development and function serving
      to remove self-reactive T-cells in the thymus as well as activated peripheral T
      cells when they are no longer required in the immune response. Evidence from the
      study of several pathogenic bacteria indicate that induction of premature cell
      death by apoptosis may be an important pathogenic mechanism promoting infection,
      inflammation and concomitant disease. In this paper we demonstrate that cultures
      of the periodontal pathogen Porphyromonas gingivalis (P. gingivalis) promote
      lymphocyte apoptosis in peripheral blood mononuclear cells (PBMC). We have used
      assays designed to investigate the different molecular and cellular changes
      associated with apoptosis. Thus flow cytometry revealed that whole cultures of P.
      gingivalis promoted cell shrinkage in the lymphocyte fraction of PBMC and
      analysis of hypodiploidy confirmed that the cellular changes were associated with
      nuclear changes characteristic of apoptosis. We also found that apoptosis was
      promoted in PBMC exposed to both whole P. gingivalis cultures and culture
      supernatant but not washed bacterial cells; this indicates that molecule(s)
      secreted into the medium were responsible for this activity and not a factor
      intrinsic to the bacterial cell. Furthermore heat treatment has no effect on the
      ability of P. gingivalis cultures to induce lymphocyte apoptosis. In summary, a
      soluble heat stable component of the supernatant from P. gingivalis cultures
      promotes lymphocyte apoptosis. These data establish the principle that bacteria
      induced apoptosis may be an important feature of the pathogenesis of periodontal
      disease.

PMID- 10207836
TI  - Calibration of the Periotron 8000 and 6000 by polynomial regression.
AB  - This paper reports the detailed calibration of the new Periotron 8000 with
      different fluids and uses the method of least squares to derive polynomial
      regression equations up to the 6th order, to investigate the most accurate
      descriptor of the resulting calibration lines. The use of a 4th order polynomial
      regression equation (recommended by the manufacturer) provided better
      coefficients of determination (R2: 0.999) and root mean square errors (RMSE =
      1.6) than either linear regression (R2: 0.986, RMSE = 10.9) or quadratic models
      (R2: 0.998, RMSE = 3.2). Data derived using the manufacturer's MLCONVERT software
      program lacked accuracy and incurred large errors for volumes > 0.5 microliter.
      Calibrations performed on one day could be used with accuracy to derive volumes >
      0.1 microliter collected on subsequent days, when using the same machine (s.d.
      for residuals plot = 2.49 Periotron units), but this was not the case for
      different machines (s.d. = 9.57 Periotron units). Varying serum protein
      concentration by up to 500% had a negligible effect on calculated volumes above
      0.1 microliter. We conclude that the Periotron 8000 is at least as reliable a
      machine as the Periotron 6000, and that the calibration lines for both machines
      are best described using 4th order polynomial regression equations and "look-up"
      tables, rather than quadratic (Periotron 6000) or the manufacturer's software
      (Periotron 8000). Serum seems to be an acceptable GCF substitute for
      calibrations, which can be performed 1 day, and used on subsequent days for a
      given machine and for volumes above 0.1 microliter.

PMID- 10207837
TI  - The proteoglycans of human cementum: immunohistochemical localization in healthy,
      periodontally involved and ageing teeth.
AB  - Cementum is believed to play a regulatory role in periodontal regeneration
      through a variety of macromolecules present in its extracellular matrix (ECM),
      among which are the proteoglycans (PG). The PG of human cementum have not been
      fully characterized. This study has used a standard indirect immunoperoxidase
      technique to investigate the presence and distribution of PG species within the
      ECM of human cementum. Freshly extracted human permanent teeth were separated
      into 8 age groups; each group was subdivided to include healthy and periodontally
      involved teeth, which were then fixed, demineralized and wax-embedded. Sections
      were incubated with polyclonal antibodies recognizing protein core epitopes in
      the large chondroitin sulphate PG versican and the small interstitial PG decorin,
      biglycan, fibromodulin and lumican. Immunoreactivity to versican, decorin,
      biglycan and lumican was evident at the borders and lumina of a proportion of
      lacunae and canaliculi surrounding cementocytes in cellular cementum, as well as
      on inserted periodontal ligament (PDL) fibres. Biglycan was also present along
      incremental lines in cellular cementum, whereas staining for fibromodulin was
      negative. In acellular cementum, no immunoreactivity was evident with any of the
      antibodies used except on inserted PDL fibres. These results indicate that
      versican, decorin, biglycan and lumican are components of the ECM of cellular,
      but not of acellular cementum. Neither age nor periodontal diseases appear to
      qualitatively influence the PG population of cementum. The distribution of PG
      epitopes around a proportion of cementocytes suggests the existence of different
      cementocyte subpopulations, or a differential response of these cells to yet
      undefined stimuli.

PMID- 10207838
TI  - Prostaglandin E2 and I2 regulate intercellular adhesion molecule-1 expression in
      interleukin-1 beta-stimulated human gingival fibroblasts.
AB  - The present study investigated the effect of prostaglandin (PG) E2 and PGI2 on
      intercellular adhesion molecule-1 (ICAM-1) expression in interleukin-1 beta (IL-1
      beta)-stimulated human gingival fibroblasts (HGF). IL-1 beta potently induced
      ICAM-1 expression in HGF and indomethacin, a cyclooxygenase inhibitor, enhanced
      ICAM-1 expression in the cells. These data showed that endogenous PGs generated
      by HGF stimulated with IL-1 beta downregulated ICAM-1 expression. IL-1 beta
      significantly increased the levels of PGE2 and, to a lesser extent, those of 6
      keto-PGF1 alpha (a stable metabolite of PGI2) in the culture media of HGF.
      Indomethacin completely inhibited the production of PGE2 and 6-keto-PGF1 alpha in
      IL-1 beta-stimulated HGF. Exogenous PGE2 and carbacyclin (a stable derivative of
      PGI2) in the presence of indomethacin dose-dependently suppressed ICAM-1
      expression in IL-1 beta-challenged HGF. Since PGE2 and PGI2 are known to elevate
      intracellular cyclic AMP (cAMP) levels, we examined the effect of dibutyryl cAMP,
      a cAMP analogue, and isobutylmethylxanthine, a phosphodiesterase inhibitor, on
      ICAM-1 expression. Both agents downregulated ICAM-1 expression in IL-1 beta
      stimulated HGF. These results suggest that PGE2 and PGI2 downregulate ICAM-1
      expression in IL-1 beta-stimulated HGF through a cAMP-dependent mechanism and
      that intracellular cAMP elevation in HGF may control inflammatory and immune
      responses in periodontal disease.

PMID- 10207839
TI  - Induction of anti-thymocyte/T lymphocyte antibodies in mice injected with
      lipopolysaccharides from periodontopathic bacteria.
AB  - We examined the levels of anti-thymocyte/T lymphocyte autoantibody (ATA) in the
      serum of mice injected intraperitoneally with lipopolysaccharides (LPS) from
      periodontopathic bacteria; Porphyromonas gingivalis, Actinobacillus
      actinomycetemcomitans, Fusobacterium nucleatum, Capnocytophaga ochracea, and non
      oral Escherichia coli. All of the LPS induced IgM-ATA. Among these, LPS from C.
      ochracea induced the highest level of IgM-ATA, whereas that of P. gingivalis
      induced the lowest. The peritoneal T lymphocytes of mice injected with LPS were
      bound by IgM-ATA. Peritoneal B-1 (CD5+B) cells stimulated by each LPS produced
      much more IgM-ATA than splenic B-2 (CD5-B) cells, suggesting that B-1 cells might
      be responsible for the production of these antibodies. Serum of mice injected
      with C. ochracea and F. nucleatum LPS showed cytotoxicity against thymocytes in
      the presence of rabbit complements. Binding and cytotoxicity were confirmed by
      IgM purified from serum of the mice injected with C. ochracea LPS. Furthermore,
      serum of mice treated with C. ochracea, F. nucleatum or A. actinomycetemcomitans
      LPS inhibited the proliferation of thymocytes. However, purified IgM from the
      serum of mice treated with C. ochracea LPS failed to produce the same inhibition.
      Our results suggest that LPS from certain species of periodontopathic bacteria
      can induce IgM-ATA in the serum and these antibodies may modulate the local
      immune network in periodontal tissues.

PMID- 10207840
TI  - Expression of transforming growth factor-beta receptors types II and III within
      various cells in the rat periodontium.
AB  - This study reports the immunohistochemical localization of TGF-beta receptor type
      II (T beta R-II) and type III (T beta R-III) in cells of the forming periodontal
      ligament (PDL) in rat first molar roots. Mandibular periodontium was obtained
      from 3, 6 and 12-wk-old rats. This represented tissue from the initial, pre
      mature and post-mature stages of root and periodontal development, respectively.
      Mandibular bone chips and molar roots were used to isolate osteoblasts,
      fibroblasts and cementoblasts. Cells were obtained using a 2-step trypsinization
      and explant technique, and cultured in Dulbecco's modification of Eagle's medium
      (DMEM) under routine cell culture conditions. Cells were cultured on coverslips
      for the purpose of detecting TGF-beta receptors, and compared with whole tissue
      sections using the same detection method. Cells which stained positively for T
      beta R-II and T beta R-III on both paraffin sections and cultured cell slides
      were counted. Both receptors were expressed in the various periodontal tissue
      compartments. PDL fibroblasts, cementoblasts and osteoblasts were stained
      positively for T beta R-II and T beta R-III. Endothelial cells were noted to be
      positive for T beta R-II only. T beta R-II was more widely distributed in cells
      than T beta R-III, but T beta R-III was extensively localized in the
      extracellular matrix. Both receptors were expressed on the cell membrane and also
      localized in the cytoplasm. The findings for paraffin sections were consistent
      with the immunohistochemical staining of cultured cells. The percentage of cells
      which stained positively for T beta R-II was greater (approximately 85%) than
      that for T beta R-III (approximately 60%) in all major types of the PDL cells on
      both paraffin sections and cultured cell slides. Extensive location of TGF-beta
      receptors in both cells and extracellular matrix suggests that several binding
      sites are available for TGF-beta s to interact with target cells during
      development and following maturation of the periodontium.

PMID- 10207841
TI  - Alkaline phosphatase activity is upregulated in regenerating human periodontal
      cells.
AB  - The activity of alkaline phosphatase (ALP) is considered to indicate the presence
      of osteoblast cells and the formation of new bone. In the present study this
      enzyme was investigated in cells obtained from retrieved polytetrafluoroethylene
      membranes (M cells) of periodontal disease patients treated by guided tissue
      regeneration (GTR) and from the regenerated tissue underlying the membrane (RT
      cells). Normal periodontal ligament (PL) and gingival cells were also grown from
      the corresponding healthy tissues of human subjects. ALP activity was measured
      colourimetrically, using paranitrophenyl phosphate as the substrate, after 4 and
      7 d of culture in the absence and presence of dexamethasone (DEX), a synthetic
      glucocorticoid which induces osteoblast differentiation. The results showed that
      basal levels of ALP activity were expressed by all the cells and that DEX
      upregulated ALP levels in the M, RT and PL cells but not in the gingival cells.
      Moreover, both the basal and DEX-induced ALP activities were statistically
      significantly higher in the RT cells than in any of the other cells. Our results
      suggest that both the GTR-associated and normal PL cells express osteoblast-like
      characteristics and, furthermore, that the RT cultures in particular contain a
      high proportion of osteoprogenitor cells.

PMID- 10207842
TI  - [Insulin resistance and metabolic syndrome in first-degree relatives of patients
      with NIDDM].
AB  - BACKGROUND: Relatives of type 2 diabetes mellitus (DM2) patients present or can
      develop the plurimetabolic syndrome (MS). Insulin sensitivity determination could
      be useful to detect relatives with higher risk. PATIENTS AND METHODS: Insulin
      sensitivity (IS) and MS in 106 first degree relatives of DM2 and 52 control
      subjects, matched for age, sex and body mass index (BMI). Insulin sensitivity was
      evaluated by the HOMA method. Insulin sensitivity was classified as high, middle
      or low according to the percentiles 33 and 66 observed in the control group. MS
      was diagnosed if hyperglycemia, hypertension, hypertriglyceridemia and overweight
      (two or more) were present. RESULTS: Insulin sensitivity was lower in relatives
      (36.3 vs 51.8%; p = 0.0001). Relatives with lower insulin sensitivity (n = 56)
      have higher BMI (29.2 vs 25.6 kg/m2), higher systolic (128 vs 116 mmHg) and
      diastolic (80 vs 74) blood pressure, hyperglycemia (5.7 vs 5.1 mmol/l),
      hyperinsulinemia (116 vs 59 pmol/l) and hypertriglyceridemia (1.4 vs 1.0 mmol/l)
      when compared with the remainder relatives (n = 50). Age, sex, waist/hip ratio
      and cholesterol level were similar in both groups. 23 relatives have MS (20 of
      them with low insulin sensitivity, relative risk = 8.7; 95% confidence interval
      2.4-31.6). In multiple logistic regression analysis, only age and IS have a
      significant value to predict the presence of MS. CONCLUSIONS: Relatives of DM2
      are insulin-resistant and present a high prevalence of MS. Both insulin
      sensitivity and MS are highly correlated. Insulin sensitivity evaluation using a
      simple methodology like HOMA can be useful in the selection of relatives at
      higher risk of MS.

PMID- 10207843
TI  - [Circadian rhythms variability of arterial pressure: methodological aspects for
      the measurement].
AB  - BACKGROUND: To study the differences among the methods used for estimating
      daytime and nighttime ambulatory blood pressure values, and to analyze their
      determinant factors. SUBJECTS AND METHODS: In 402 individuals mean values of
      systolic and diastolic blood pressure (SBP and DBP) during 24 h, daytime and
      nighttime, were calculated by three different methods: a) real-time, following a
      minidiary; b) long-time, having a nighttime period from 23:00 to 07:00 h, and a
      daytime one from 08:00 to 22:00 h, and c) short-time, having a nighttime period
      from midnight to 6:00 h, and a daytime one from 08:00 to 22:00 h. RESULTS:
      Daytime mean values of SBP and DBP were similar for the three methods. Nighttime
      mean values of SBP and DBP calculated using the long-time were significantly
      higher than those calculated with the real-time ((SBP -2.25 [5.3] mmHg, p < 0.05;
      DBP -1.17 [3.4] mmHg, p < 0.05). No differences were observed for both SBP and
      DBP with the real-time. The number of sleeping hours was the main determinant of
      the differences observed between the long-time and the real-time methods. The
      percentage of subjects with a non-dipping pattern were 17, 26 and 18% for real,
      long and short time methods, respectively. CONCLUSIONS: Daytime mean BP values
      are reproducible whatever the method used, but for estimating nighttime mean BP
      values short-time is the best of the fixed-time methods. Minidiary should be used
      if more accurate values are necessary or if the subjects sleep habits do not fit
      into the standard patterns.

PMID- 10207845
TI  - [Arterial pressure and IDDM: what does ambulatory arterial pressure measurement
      provide?].

PMID- 10207844
TI  - [Gly380Arg and Asn540Lys mutations of fibroblast growth factor receptor 3 in
      achondroplasia and hypochndroplasia in the Spanish population].
AB  - BACKGROUND: Achondroplasia, the most common type of genetic dwarfism
      characterised by disproportionate short stature and other skeletal anomalies,
      results from a defect in the maturation of the chondrocytes in the growth plate
      cartilage. Hypochondroplasia, considered allelic to achondroplasia is clinically
      and genetically heterogeneous. Recent studies have mapped the gene on chromosome
      4p16.3, and frequent mutations in the fibroblast growth factor 3 (FGFR3) have
      been described in these diseases in other populations. PATIENTS AND METHODS:
      Analysis of the FGFR3 gene mutations Gly380Arg and Asn540Lys in 20 Spanish
      patients (10 achondroplasic, 6 hypochondroplasic and 4 with skeletal dysplasias
      with some phenotypic and radiological characteristics of hypochondroplasia) by
      PCR and restriction analysis. RESULTS: All the achondroplasic patients have shown
      the same mutation (Gly380Arg) in the transmembrane domain of the receptor. Five
      hypochondroplasic patients presented the mutation Asn540Lys in the proximal
      thirosine kinase domain. CONCLUSIONS: Achondroplasia in this sample from Spanish
      patients is also homogeneous in its molecular basis. Genetic heterogeneity has
      been found in hypochondroplasia corresponding with the phenotypic diversity in
      this disease. Molecular analysis of FGFR3 may be an additional diagnostic tool
      and facilitates genetic counselling in these chondrodysplasias.

PMID- 10207846
TI  - [Prophylaxis of infectious endocarditis: when, how and why?].

PMID- 10207847
TI  - [Multiple endocrine neoplasia type 1: genetic study of a large family].
AB  - Multiple endocrine neoplasia syndrome type 1 (MEN-1) is an inherited disorder
      characterised by the predisposition of the cells from parathyroid glands,
      endocrine pancreas and adenohypophysis to develop neoplasms. We report the
      genetic study of an extended family with at least 8 affected patients and 10
      putative carriers of a mutation in MEN-1 gene. One intragenic (Asp418 GAC-->GAT),
      and five flanking markers were characterised in the family by PCR amplification
      and polyachrylamide gel electrophoresis. Association of the disease to MEN-1 gene
      was confirmed for this family: all the affected members show a haplotype in
      common. Three patients at risk were diagnosed as non-carriers, since they have
      not inherited that haplotype. The remaining seven members, presymptomatic
      carriers, are included in a follow-up protocol. The genetic study of families
      segregating MEN-1 syndrome are useful in avoiding indiscriminate follow-up
      determinations to those members who have not received the genetic predisposition
      to develop any of the manifestations of the syndrome. Segregation analysis with
      linked markers is useful, under certain circumstances, to perform such type of
      studies.

PMID- 10207848
TI  - [Hyperlipidemia following heart transplantation. Pathogenic mechanisms and
      treatment].

PMID- 10207849
TI  - [A 52-year-old woman with metrorrhagia and bilateral pulmonary nodules].

PMID- 10207850
TI  - [Clinical and biological differences between infiltrating mucinous and lobular
      breast carcinomas without axillary lymph node involvement].

PMID- 10207852
TI  - [Last names, English style].

PMID- 10207851
TI  - [Determination of alpha-glucosidase as a marker of epididymal function].

PMID- 10207853
TI  - [Ciprofloxacin neurotoxicity].

PMID- 10207854
TI  - [Purpura fulminans as complication of Mycoplasma pneumoniae infection].

PMID- 10207855
TI  - [Primary non-Hodgkin's lymphomas of the parotid gland. Study of 5 patients].

PMID- 10207856
TI  - [The image of the week. Tuberculous spondylodiscitis of disks 9-11 (mal de Pott)
      with ossifying abscess].

PMID- 10207857
TI  - Genetically modified muddle.

PMID- 10207858
TI  - Funding of human embryo research in the US.

PMID- 10207859
TI  - Telomere-dependent senescence.

PMID- 10207860
TI  - Food safety regulations.

PMID- 10207867
TI  - FDA slow to encourage lupus drugs.

PMID- 10207868
TI  - European Parliament considers release of GMOs.

PMID- 10207869
TI  - Glaxo's antiviral ills not deemed contagious.

PMID- 10207870
TI  - Adjusting FDA policies to address bioterrorist threat.

PMID- 10207871
TI  - FDA's interferon-beta decision reignites orphan debate.

PMID- 10207872
TI  - Complaints raised over restricted microarray access.

PMID- 10207873
TI  - Genetech enlightens other angiogenesis programs.

PMID- 10207874
TI  - Debugging expression screening.

PMID- 10207875
TI  - Transgene escape and transplastomics.

PMID- 10207876
TI  - Transposing BACs to the future.

PMID- 10207877
TI  - Colorless green ideas...

PMID- 10207878
TI  - Bioartificial organs transplanted from research to reality.

PMID- 10207879
TI  - The body as a manufacturer of endostatin.

PMID- 10207880
TI  - Encapsulating the right chemistry.

PMID- 10207881
TI  - Systemic inhibition of tumor growth and tumor metastases by intramuscular
      administration of the endostatin gene.
AB  - Tumors require ongoing angiogenesis to support their growth. Inhibition of
      angiogenesis by production of angiostatic factors should be a viable approach for
      cancer gene therapy. Endostatin, a potent angiostatic factor, was expressed in
      mouse muscle and secreted into the bloodstream for up to 2 weeks after a single
      intramuscular administration of the endostatin gene. The biological activity of
      the expressed endostatin was demonstrated by its ability to inhibit systemic
      angiogenesis. Moreover, the sustained production of endostatin by intramuscular
      gene therapy inhibited both the growth of primary tumors and the development of
      metastatic lesions. These results demonstrate the potential utility of
      intramuscular delivery of an antiangiogenic gene for treatment of disseminated
      cancers.

PMID- 10207882
TI  - A single adenovirus vector mediates doxycycline-controlled expression of tyrosine
      hydroxylase in brain grafts of human neural progenitors.
AB  - Ex vivo gene transfer is emerging as a promising therapeutic approach to human
      neurodegenerative diseases. By combining efficient methodologies for cell
      amplification and gene delivery, large numbers of cells can be generated with the
      capacity to synthesize therapeutic molecules. These cells can then be
      transplanted into the degenerating central nervous system (CNS). Applying this
      approach to human diseases will require the development of suitable cellular
      vehicles, as well as safe gene delivery systems capable of tightly controlled
      transgene expression. For such brain repair technologies, human neural
      progenitors may be extremely valuable, because of their human CNS origin and
      developmental potential. We have used these cells to develop a system for the
      regulated expression of a gene of therapeutic potential. We report the
      construction of a single adenovirus encoding human tyrosine hydroxylase 1 (hTH-1)
      under the negative control of the tetracycline-based gene regulatory system.
      Human neural progenitors infected with this vector produced large amounts of hTH
      1. Most importantly, doxycycline allowed a reversible switch of transgene
      transcription both in vitro and in vivo. This system may be applied to the
      development of therapies for human neurodegenerative diseases.

PMID- 10207883
TI  - Linear expression elements: a rapid, in vivo, method to screen for gene
      functions.
AB  - The increasing accumulation of genomic sequence information has accentuated the
      need for new methods to efficiently assess gene function and to prepare reagents
      to study these functions. Toward solving this general problem in functional
      genomics, we report a method by which any PCR-amplified open-reading frame (ORF)
      can be noncovalently linked to a eukaryotic promoter and terminator, and directly
      injected into animals to produce local gene expression. We also demonstrate that
      ORFs can be delivered into mice to produce antibodies specific for the encoded
      foreign protein by simply attaching mammalian promoter and terminator sequences.
      This technology makes it possible to screen large numbers of genes rapidly for
      their functions in vivo or to produce immune responses without the necessity of
      cloning, bacterial propagation, or protein purification.

PMID- 10207884
TI  - Rapid identification of essential and nonessential herpesvirus genes by direct
      transposon mutagenesis.
AB  - Herpesviruses are important pathogens in animals and humans. The large DNA
      genomes of several herpesviruses have been sequenced, but the function of the
      majority of putative genes is elusive. Determining which genes are essential for
      their replication is important for identifying potential chemotherapy targets,
      designing herpesvirus vectors, and generating attenuated vaccines. For this
      purpose, we recently reported that herpesvirus genomes can be maintained as
      infectious bacterial artificial chromosomes (BAC) in Escherichia coli. Here we
      describe a one-step procedure for random-insertion mutagenesis of a herpesvirus
      BAC using a Tn1721-based transposon system. Transposon insertion sites were
      determined by direct sequencing, and infectious virus was recovered by
      transfecting cultured cells with the mutant genomes. Lethal mutations were
      rescued by cotransfecting cells containing noninfectious genomes with the
      corresponding wild-type subgenomic fragments. We also constructed revertant
      genomes by allelic exchange in bacteria. These methods, which are generally
      applicable to any cloned herpesvirus genome, will facilitate analysis of gene
      function for this virus family.

PMID- 10207885
TI  - Single nucleotide polymorphic discrimination by an electronic dot blot assay on
      semiconductor microchips.
AB  - We have developed a rapid assay for single nucleotide polymorphism (SNP)
      detection that utilizes electronic circuitry on silicon microchips. The method
      was validated by the accurate discrimination of blinded DNA samples for the
      complex quadra-allelic SNP of mannose binding protein. The microchip directed the
      transport, concentration, and attachment of amplified patient DNA to selected
      electrodes (test sites) creating an array of DNA samples. Through control of the
      electric field, the microchip enabled accurate genetic identification of these
      samples using fluorescently labeled DNA reporter probes. The accuracy of this
      approach was established by internal controls of dual labeled reporters and by
      using mismatched sequences in addition to the wild-type and variant reporter
      sequences to validate the SNP-genotype. The ability to customize this assay for
      multiple genes has advantages over other existing approaches.

PMID- 10207886
TI  - Chiral discrimination using an immunosensor.
AB  - Based on the stereoselectivity of immunoglobulins, we have developed a new chiral
      sensor for the detection of low-molecular-weight analytes. Using surface plasmon
      resonance detection, enantiomers of free, underivatized alpha-amino acids can be
      monitored in a competitive assay by their interaction with antibodies specific
      for the chiral center of this class of substances. The sensitivity to the minor
      enantiomer in nonracemic mixtures exceeds currently available methods; therefore,
      such immunosensors can readily detect traces of enantiomeric impurities and are
      attractive for a range of applications in science and industry.

PMID- 10207887
TI  - In vivo imaging of tumors with protease-activated near-infrared fluorescent
      probes.
AB  - We have developed a method to image tumor-associated lysosomal protease activity
      in a xenograft mouse model in vivo using autoquenched near-infrared fluorescence
      (NIRF) probes. NIRF probes were bound to a long circulating graft copolymer
      consisting of poly-L-lysine and methoxypolyethylene glycol succinate. Following
      intravenous injection, the NIRF probe carrier accumulated in solid tumors due to
      its long circulation time and leakage through tumor neovasculature. Intratumoral
      NIRF signal was generated by lysosomal proteases in tumor cells that cleave the
      macromolecule, thereby releasing previously quenched fluorochrome. In vivo
      imaging showed a 12-fold increase in NIRF signal, allowing the detection of
      tumors with submillimeter-sized diameters. This strategy can be used to detect
      such early stage tumors in vivo and to probe for specific enzyme activity.

PMID- 10207888
TI  - Directed evolution of a fungal peroxidase.
AB  - The Coprinus cinereus (CiP) heme peroxidase was subjected to multiple rounds of
      directed evolution in an effort to produce a mutant suitable for use as a dye
      transfer inhibitor in laundry detergent. The wild-type peroxidase is rapidly
      inactivated under laundry conditions due to the high pH (10.5), high temperature
      (50 degrees C), and high peroxide concentration (5-10 mM). Peroxidase mutants
      were initially generated using two parallel approaches: site-directed mutagenesis
      based on structure-function considerations, and error-prone PCR to create random
      mutations. Mutants were expressed in Saccharomyces cerevisiae and screened for
      improved stability by measuring residual activity after incubation under
      conditions mimicking those in a washing machine. Manually combining mutations
      from the site-directed and random approaches led to a mutant with 110 times the
      thermal stability and 2.8 times the oxidative stability of wild-type CiP. In the
      final two rounds, mutants were randomly recombined by using the efficient yeast
      homologous recombination system to shuffle point mutations among a large number
      of parents. This in vivo shuffling led to the most dramatic improvements in
      oxidative stability, yielding a mutant with 174 times the thermal stability and
      100 times the oxidative stability of wild-type CiP.

PMID- 10207889
TI  - Expression of an engineered form of recombinant procollagen in mouse milk.
AB  - We have examined the suitability of the mouse mammary gland for expression of
      novel recombinant procollagens that can be used for biomedical applications. We
      generated transgenic mouse lines containing cDNA constructs encoding recombinant
      procollagen, along with the alpha and beta subunits of prolyl 4-hydroxylase, an
      enzyme that modifies the collagen into a form that is stable at body temperature.
      The lines expressed relatively high levels (50-200 micrograms/ml) of recombinant
      procollagen in milk. As engineered, the recombinant procollagen was shortened and
      consisted of a pro alpha 2(I) chain capable of forming a triple-helical
      homotrimer not normally found in nature. Analysis of the product demonstrated
      that (1) the pro alpha chains formed disulphide-linked trimers, (2) the trimers
      contained a thermostable triple-helical domain, (3) the N-propeptides were
      aligned correctly, and (4) the expressed procollagen was not proteolytically
      processed to collagen in milk.

PMID- 10207891
TI  - The patentability of algorithms.

PMID- 10207890
TI  - Low probability of chloroplast movement from oilseed rape (Brassica napus) into
      wild Brassica rapa.
AB  - Pollen-mediated movement of transgenes from transplastomic oilseed rape (Brassica
      napus) into wild relatives will be avoided if chloroplasts are maternally
      transmitted. We assess the probability of chloroplast exchange between
      conventional oilseed rape and wild Brassica rapa to model the future behavior of
      transplastomic cultivars. Primers specific to cpDNA were used to demonstrate
      maternal inheritance of chloroplasts in 47 natural hybrids between cultivated B.
      napus and wild B. rapa. We conclude that there will be no or negligible pollen
      mediated chloroplast dispersal from oilseed rape. Transgene introgression could
      still occur in mixed populations, however, if B. napus acted as the recurrent
      female parent. Rate of transfer would then depend on the abundance of mixed
      populations, their persistence as mixtures, and hybridization frequency within
      stands. A low incidence of sympatry (0.6-0.7%) between wild B. rapa and
      cultivated B. napus along the river Thames, UK, in 1997 and 1998, suggests mixed
      stands will form only rarely. Eighteen feral populations of B. napus also showed
      a strong tendency toward rapid decline in plant number, seed return, and
      ultimately, extinction within 3 years. Conversely, hybrid production is
      significant in mixed stands, and the absence of control practices means that
      oilseed rape will have slightly greater persistence. We infer that some
      introgression from transplastomic B. napus into B. rapa is inevitable in mixed
      populations even though such populations will occur infrequently and will tend to
      lose B. napus plants relatively quickly. Chloroplast exchange will be extremely
      rare and scattered.

PMID- 10207892
TI  - Selection of high-affinity phage antibodies from phage display libraries.

PMID- 10207893
TI  - Antisense therapeutics.

PMID- 10207894
TI  - Gap junction-mediated intercellular signalling in health and disease. Proceedings
      of a meeting. London, United Kingdom, 2-5 March 1998.

PMID- 10207895
TI  - Molecular biology of the interactions between connexins.
AB  - The protein structural component of gap junctions is the connexin. Studies on the
      association properties of the connexins to form heteromeric connexons and
      heterotypic gap junctions are necessary for a complete understanding of the role
      of different connexins in gap junction function. The connexins are coded by a
      multigene family consisting of at least 16 members. Most cells express multiple
      types of connexin that can potentially associate to form gap junction channels
      containing more than one type of connexin. The permeability and gating
      characteristics of gap junction channels are dependent on the isoform and post
      translational modifications present on the connexins and their association
      properties. Together with an observed selectivity in the association properties
      of the different connexins and the development of more specific perturbation
      approaches, these studies have provided insights into the significance of
      connexin diversity and the temporal expression patterns for connexins that have
      been determined in vivo in both developmental and differentiating systems.

PMID- 10207896
TI  - Electron cryo-crystallography of a recombinant cardiac gap junction channel.
AB  - Gap junctions in the heart play an important functional role by electrically
      coupling cells, thereby organizing the pattern of current flow to allow co
      ordinated muscle contraction. Cardiac gap junctions are therefore intimately
      involved in normal conduction as well as the genesis of potentially lethal
      arrhythmias. We recently utilized electron cryo-microscopy and image analysis to
      examine frozen-hydrated 2D crystals of a recombinant, C-terminal truncated form
      of connexin 43 (Cx43; alpha 1), the principal cardiac gap junction protein. The
      projection map at 7 A resolution revealed that each 30 kDa connexin subunit has a
      transmembrane alpha-helix that lines the aqueous pore and a second alpha-helix in
      close contact with the membrane lipids. The distribution of densities allowed us
      to propose a model in which the two apposing connexons that form the channel are
      staggered by approximately 30 degrees. We are now recording images of tilted,
      frozen-hydrated 2D crystals, and a preliminary 3D map has been computed at an in
      plane resolution of approximately 7.5 A and a vertical resolution of
      approximately 25 A. As predicted by our model, the two apposing connexons that
      form the channel are staggered with respect to each other for certain connexin
      molecular boundaries within the hexamer. Within the membrane interior each
      connexin subunit displays four rods of density, which are consistent with an
      alpha-helical conformation for the four transmembrane domains. Preliminary
      studies of BHK hamster cells that express the truncated Cx43 designated alpha 1
      Cx263T demonstrate that oleamide, a sleep inducing lipid, blocks in vivo dye
      transfer, suggesting that oleamide causes closure of alpha 1 Cx263T channels. The
      comparison of the 3D structures in the presence and absence of oleamide may
      provide an opportunity to explore the conformational changes that are associated
      with oleamide-induced blockage of dye transfer. The structural details revealed
      by our analysis will be essential for delineating the molecular basis for
      intercellular current flow in the heart, as well as the general molecular design
      and functional properties of this important class of channel proteins.

PMID- 10207898
TI  - Interactions between growth factors and gap junctional communication in
      developing systems.
AB  - In the vertebrate limb bud fibroblast growth factor (FGF) 4 secreted by cells of
      the posterior apical ectodermal ridge controls digit pattern, which is directed
      by polarizing cells in the posterior mesenchyme at the tip of the bud. FGF4 also
      controls the expression of gap junctions in the limb. Both chick and mouse limb
      bud mesenchyme express connexin 32 (Cx32; beta 1) and Cx43 (alpha 1), although
      not in the same gap junction plaques. Quantitative analysis reveals two gradients
      of gap junctions: from posterior to anterior in the subapical mesenchyme and from
      distal to proximal along the bud. The highest gap junction density is associated
      with the polarizing region. Micromass cultures of chick and mouse posterior and
      anterior mesenchyme cells were used to assess the ability of FGF4 to modulate gap
      junctional communication. Posterior mesenchyme (polarizing region) cells express
      a population of gap junctions that are highly sensitive to FGF4, whereas gap
      junctions between anterior mesenchyme cells are completely insensitive to FGF4.
      FGF4 doubles gap junction density, intercellular communication and the polarizing
      capacity of posterior mesenchyme cells, restoring polarizing capacity to in vivo
      levels. We conclude that gap junctional communication and polarizing capacity are
      intimately linked. Interactions between signalling molecules and junctional
      communication may play an important role in controlling development.

PMID- 10207897
TI  - Trafficking pathways leading to the formation of gap junctions.
AB  - This chapter reports the mechanisms resulting in the assembly of gap junction
      intercellular communication channels. The connexin channel protein subunits are
      required to oligomerize into hexameric hemichannels (connexons) that may be
      homoor heteromeric in composition. Pairing of connexons in contacting cells leads
      to the formation of a gap junction unit. Subcellular fractionation studies using
      guinea-pig liver showed that oligomerization of connexins was complete on entry
      into Golgi, and that connexons showed heteromeric properties. The low ratio of
      connexin26 (Cx26; beta 2) relative to Cx32 (beta 1) in endomembranes compared to
      the approximately equal ratios found in plasma membranes and gap junctions
      suggest that Cx26 takes a non-classical route to the plasma membrane. Cultured
      cells, expressing connexin-aequorin chimeras, also provided evidence that Cx26
      takes a more rapid non-classical route to the plasma membrane, because brefeldin
      A, a drug that disrupts the Golgi, had minimal effects on trafficking of Cx26 to
      the plasma membrane in contrast to its disruption of Cx32 trafficking. Finally, a
      cell-free approach for studying synthesis of connexons provided further evidence
      that Cx26 showed membrane insertion properties compatible with a more direct
      intracellular route to gap junctions. The presence of dual gap junction assembly
      pathways can explain many of the differential properties exhibited by connexins
      in cells.

PMID- 10207899
TI  - Biological functions of connexin genes revealed by human genetic defects,
      dominant negative approaches and targeted deletions in the mouse.
AB  - Gap junction channels in mammalian organs can be built up of at least 13
      different connexin proteins, most of which are expressed in only few cell types,
      although many cells express more than one connexin protein. Recently, the
      consequences of missing or defective connexin proteins were studied in human
      patients with defects in connexin32 (Cx32; beta 1; X-linked Charcot-Marie-Tooth
      disease) or in Cx26 (beta 2; non-syndromic sensorineural deafness), and in mice
      with targeted deletions in the Cx26, Cx32, Cx37 (alpha 4), Cx43 (alpha 1), Cx46
      (alpha 3) or Cx50 (alpha 8) genes. Some effects of dominant negative mutations in
      connexin genes have been characterized in Xenopus oocytes and transfected
      mammalian cells in culture. Here we review results of these different
      experimental approaches and report new findings regarding the characterization of
      Cx40 (alpha 5)- and Cx31 (beta 3)-deficient mice. The phenotypic alterations,
      caused by different defective connexin genes in mice or humans, are divergent,
      although in most known cases the viability is not affected. When more than one
      connexin gene, coexpressed in the same cell, is inactivated, development or
      maturation can be more severely affected at an earlier stage. Some connexin
      proteins, if present in the same cell, can partially replace each other in
      certain functions. Thus, the diversity of connexin proteins in mammalian cells
      may provide functional overlap and complementation.

PMID- 10207900
TI  - Connexins in the lens: are they to blame in diabetic cataractogenesis?
AB  - The pathohistology of the diabetic lens is an enigma. Under normal conditions the
      lens behaves as a functional syncitium, whereas the diabetic lens exhibits a
      localized zone of fibre cell swelling and rupture that is confined to the lens
      outer cortex. Because the lens fibre cells are extensively coupled by gap
      junction channels, it is believed that the abnormal closure of these channels is
      responsible for this phenomenon. New evidence concerning regional differences in
      gap junction gating supports this contention, and it is used to propose a new
      hypothesis that may explain the cellular changes observed in the diabetic lens.

PMID- 10207901
TI  - Neuronal coupling in the central nervous system: lessons from the retina.
AB  - The retina is a model system for studying gap junctional intercellular
      communication in the CNS. The cellular coupling can be graphically visualized in
      retinal whole mounts by injecting small cationic tracers into microscopically
      identified neurons; the pattern of tracer coupling shown by each type of retina
      neuron is highly stereotyped, with many types of amacrine cells and ganglion
      cells showing complex patterns of both homologous and heterologous coupling.
      Parallel physiological studies have demonstrated that the gap junctions can be
      modulated dynamically by neurotransmitters and by the level of ambient
      illumination. Taken together, the numerous structural and functional studies on
      gap junctions in the retina provide powerful support for the concept that
      electrical synapses are complex components of neuronal circuits, having many of
      the attributes normally ascribed to chemical synapses.

PMID- 10207903
TI  - Gap junction-mediated communication in the developing and adult cerebral cortex.
AB  - Recent cell biological and electrophysiological studies have shown that gap
      junctional coupling and the proteins that mediate this form of communication are
      present in the developing cerebral cortex from early in corticogenesis to the
      later stage of neuronal circuit formation. We have used electron microscopy to
      visualize gap junctions in the developing rat cerebral cortex, and studied the
      expression patterns and cellular localizations of connexin26 (Cx26; beta 2), Cx32
      (beta 1) and Cx43 (alpha 1), which take part in their formation. We found that
      these connexins are expressed differentially during development, and their
      patterns of expression are correlated with important developmental events such as
      cell proliferation, migration and formation of cortical neuronal circuits. We
      also observed that gap junctions and their constituent connexins were abundant in
      the adult cerebral cortex. Junctions were predominantly between glial cells or
      between neurons and glia. The frequency and distribution of gap junctions varied
      in different regions of the adult cortex, possibly reflecting differences in the
      cellular and functional organization of these cortical areas.

PMID- 10207902
TI  - Gap junctions and connexin expression in the inner ear.
AB  - Several different recessive mutations in the connexin26 (Cx26; beta 2) gene have
      been associated with non-syndromic hereditary deafness. This suggests gap
      junctions are important to cochlear function. Numerous large gap junctions are
      present between adjacent supporting cells in both the vestibular and auditory
      sensory epithelia of the mature inner ear. In vestibular organs, Cx26 is highly
      expressed, but antibodies of Cx32 (beta 1) also label the supporting cells. In
      the organ of Corti of the cochlea, Cx26 is the predominant connexin isoform;
      neither Cx32 nor Cx43 (alpha 1) can be detected by immunohistochemistry. One role
      for gap junctions between supporting cells may be to provide a pathway for the
      rapid removal of ions away from the region of the sensory cells during
      transduction in order to maintain sensitivity. In the cochlea gap junctions are
      also associated with the basal cells of the stria vascularis, an ion-transporting
      epithelium that maintains a positive electrical potential in the potassium-rich
      endolymph fluid which bathes the apical surfaces of the sensory 'hair' cells and
      which is crucial for auditory transduction. Gap junctions are present between
      fibrocytes in the spiral ligament that underlies the stria vascularis, and
      between these fibrocytes and strial basal cells. During cochlear development, the
      initial formation and subsequent increase in size and number of gap junctions in
      the stria vascularis coincides with the initial generation and rise of the
      endocochlear potential. This and other evidence suggests that one role of gap
      junctions in the cochlea is to provide a pathway for passage of ions to maintain
      endolymph and, thus, auditory acuity. Mutations to Cx26 could, therefore, disrupt
      this ion circulation, resulting in deafness.

PMID- 10207904
TI  - The role of the gap junction protein connexin32 in the pathogenesis of X-linked
      Charcot-Marie-Tooth disease.
AB  - Mutations in the gene encoding the gap junction protein connexin32 (Cx32; beta 1)
      cause the X-linked form of Charcot-Marie-Tooth disease (CMTX), a common form of
      inherited demyelinating neuropathy. Cx32 is localized to the paranodes and
      incisures of myelinating Schwann cells, and probably participates in the
      formation of gap junctions at these locations, thereby allowing the diffusion of
      ions and small molecules directly across the myelin sheath. In transfected cells
      different CMTX mutations have different effects on the ability of the mutant
      protein to form functional gap junctions; some mutant proteins cannot be detected
      within the cell, other mutant proteins accumulate within the cell but do not
      reach the cell membrane, while other mutants reach the cell membrane and some of
      these form functional gap junctions. In transgenic mice two mutants, R142W and
      175 frameshift, have similar effects on protein trafficking as in transfected
      cells: the R142W mutant protein remains in the perinuclear region and does not
      reach the paranodes or incisures, and the 175 frameshift protein cannot be
      detected. Thus, different CMTX mutations have different effects on Cx32 protein,
      and these differences may help to explain the phenotypic differences seen in CMTX
      kindreds.

PMID- 10207905
TI  - Cardiovascular disease.
AB  - Gap junctions play essential roles in the normal function of the heart and
      arteries, mediating the spread of the electrical impulse that stimulates
      synchronized contraction of the cardiac chambers, and contributing to co
      ordination of function between cells of the arterial wall. Altered gap junctional
      coupling is implicated in the genesis of arrhythmia, a major cause of death in
      heart disease. Two abnormalities in myocardial gap junctions distribution at the
      border zone of infarcts and reduced levels of connexin43 (Cx43; alpha 1)--may
      lead to heterogeneous wavefront propagation and lowered conduction velocity, key
      factors that precipitate arrhythmia. In the major arteries, endothelial cells
      express Cx40 (alpha 5) and Cx37 (alpha 4) and, in some instances, also Cx43,
      whereas underlying medial smooth muscle cells express only Cx43. Increased Cx43
      expression between medial smooth muscle cells is intimately linked to phenotypic
      transformation to the synthetic state in both early human coronary phenotypic
      transformation to the synthetic state in both early human coronary
      atherosclerosis, and in the response of the arterial wall to injury. The
      accumulating evidence suggests that gap junctions in both their guises--as
      pathways for cell-to-cell signalling in the vessel wall and as pathways for
      impulse conduction in the heart--may have key roles in the initial pathogenesis
      and eventual clinical manifestation of human cardiovascular disease.

PMID- 10207906
TI  - Misregulation of connexin43 gap junction channels and congenital heart defects.
AB  - Although there is general agreement that gap junction channels formed by the
      connexin43 (Cx43; alpha 1) protein most likely have important roles during heart
      development, evidence to support this view has been equivocal. Lacking this
      information, it is difficult to understand the basis of heart malformations found
      in the Cx43 knockout mice and in children with a severe form of visceroatrial
      heterotaxia that coincides with missense mutations of the Cx43 gene. To address
      this issue we used a combination of western blots to follow the emergence of Cx43
      in heart, and in vitro and in vivo phosphorylation to assess the effect of
      mutation on Cx43 phosphorylation. We evaluated the activity ratios of cAMP
      dependent protein kinase and protein kinase C in hearts of 8.5-day-old mouse
      embryos through to birth. The results demonstrate that Cx43 is present in the
      native phosphorylated species in day 8.5 hearts and thereafter. Further, the
      activities of cAMP-dependent protein kinase and protein kinase C are mirror
      images of each other during the 8.5-10.5 days of early heart development. From
      these results we conclude that Cx43 gap junction channels are present and capable
      of being regulated by day 8.5 of embryonic heart development.

PMID- 10207907
TI  - Gap junctional intercellular communication in the mouse ovarian follicle.
AB  - A targeted disruption of the gene encoding the gap junction protein connexin37
      (Cx37; alpha 4) results in female infertility. Mutant follicles are not observed
      to develop beyond early antral stages, and there is a lack of both observable
      mature Graafian follicles and ovulation. The oocytes are unable to acquire
      meiotic competence. Following oocyte failure, the residual follicular cells do
      not undergo atresia but rather transdifferentiate into luteal cells, resulting in
      a mutant ovary populated with numerous, inappropriate corpora lutea. These
      results indicate that the Cx37-containing gap junctions formed between oocyte and
      follicular cells permit bidirectional signalling between the two cell types.
      These junctions are required for oocyte growth and development during preantral
      stages of the follicle, and for the inhibition of follicle cell luteinization. An
      additional role for these junctions may be to permit transfer of cytoplasmic
      signals required to hold oocytes in meiotic arrest. Since the mutant follicles
      never acquire meiotic competence, this latter role for gap junctional
      communication cannot be tested in this model.

PMID- 10207908
TI  - Connexins in tumour suppression and cancer therapy.
AB  - Malignant cells usually show altered gap junctional intercellular communication
      and are often associated with aberrant expression or localization of connexins.
      Transfection of connexin genes into tumorigenic cells restores normal cell
      growth, suggesting that connexins form a family of tumour suppressor genes. Some
      studies have also shown that specific connexins may be necessary to control
      growth of specific cell types. Although we have found that genes encoding
      connexin32 (Cx32; beta 1), Cx37 (alpha 4) and Cx43 (alpha 1) are rarely mutated
      in tumours, our recent studies suggest that methylation of the connexin gene
      promoter may be a mechanism by which connexin gene expression is down-regulated
      in certain tumors. We have produced various dominant negative mutants of the
      genes encoding Cx26 (beta 2), Cx32 and Cx43, some of which prevent the growth
      control exerted by the corresponding wild-type genes. A decade ago, we proposed a
      method to enhance killing of cancer cells by diffusion of therapeutic agents
      through gap junctions. Recently, we and others have shown that gap junctional
      intercellular communication is responsible for the bystander effect seen in
      herpes simplex virus thymidine kinase/ganciclovir gene therapy. Thus, connexin
      genes can exert dual effects in tumour control: tumour suppression and a
      bystander effect for cancer therapy.

PMID- 10207909
TI  - Bacterial response to pH. Introduction.

PMID- 10207910
TI  - Problems of adverse pH and bacterial strategies to combat it.
AB  - This chapter aims to survey the problems faced by bacteria found in environments
      of adverse pH, to review strategies used to combat those problems and to ask how
      those strategies are implemented. At acid or alkaline pH, bacteria are challenged
      not just by excess of H+ or OH- but also by excess of metal ions (aluminium,
      heavy metals at acidic pH, Na+ at alkaline pH), as well as shortages. Bacteria
      attempt to maintain their intracellular pH by minimizing membrane permeability to
      H+ and other ions, buffering the cytoplasm, ameliorating the external pH through
      catabolism or selective substrate utilization, and developing ionic pumping
      systems. The amelioration of pH depends on the availability of substrate, and is
      unlikely in most naturally stressful environments. Ion pumping is expensive
      energetically, although the cost to growth is unknown. The response to adverse pH
      involves sensing systems and responsive regulatory systems. The adaptive acid
      tolerance response is now well known in and other bacteria, but is there a
      widespread adaptive alkali tolerance response? What and where are the sensors?
      Whether they sense intracellular pH, extracellular pH or delta pH is unclear,
      although an external sensory input seems essential. Is there one major sensory
      system responsive to pH or multiple systems with back-up mechanisms? What and
      where are the regulators? Is there one central regulator controlling all the
      responses or are there cascades of responses?

PMID- 10207911
TI  - The regulation of intracellular pH in bacteria.
AB  - The regulation of intracellular pH (pHi) in bacterial cells is achieved through
      control over cation (and anion) permeability. In addition to the active
      components of homeostasis there are contributions from essentially passive
      elements, such as the lipid composition of the membrane and the buffering
      capacity of the cytoplasm. Active homeostasis involves control over the movement
      of K+, Na+ and H+. Alterations in the membrane permeability for any of these
      cations may cause perturbation of homeostasis. In Escherichia coli this is
      exemplified by the controlled activation of K+ efflux systems by glutathione
      adducts leading to temporary acidification of the cytoplasm. This is achieved by
      sophisticated control over the KefB and KefC systems, and is tightly integrated
      with glutathione-dependent detoxification mechanisms. Such control over pHi
      facilitates survival of the cell following exposure to toxic electrophiles. The
      components of pH homeostasis will be reviewed and the molecular mechanisms, and
      role of, the KefB and KefC systems will be discussed.

PMID- 10207912
TI  - pH sensing in bacterial chemotaxis.
AB  - Bacteria are able to sense a broad range of chemical and energetic stimuli and
      modulate their swimming behaviour to migrate to more favourable environments.
      Signal transduction in bacterial chemotaxis is mediated by a two-component system
      composed of a protein histidine kinase, CheA, and a response regulator, CheY. The
      phosphorylated response regulator, P approximately CheY, binds to a protein at
      the flagellar motor, FliM, to cause reversals in flagellar motor rotation. The
      level of P approximately CheY is controlled by the activity of the kinase CheA,
      which is in turn regulated by membrane receptors at the cell surface. Membrane
      receptors such as the aspartate receptor, Tar, are composed of two distinct
      regions: an extracellular sensing domain that binds stimulatory ligands,
      aspartate in the case of Tar; and an intracellular signalling domain that forms a
      complex with the protein kinase CheA. What is the mechanism of transmembrane
      signalling? How does aspartate binding to the sensing domain at the outside
      surface of the membrane translate into a change in kinase activity at the
      membrane cytosol interface? Recent results suggest that the mechanism depends on
      perturbations in lateral packing within an extensive array of receptors localized
      to patches at the cell poles. Receptor patching appears to depend on higher-order
      associations with the kinase CheA as well as an adaptor protein, CheW. It is
      difficult to assess the locus of pH effects within the context of even a simple
      signal transduction system like that involved in bacterial chemotaxis. Previous
      results with mutant strains have indicated that the serine receptor, Tsr, is
      critical for pH sensing, but in vitro results do not support such a
      straightforward interpretation of the genetic data.

PMID- 10207913
TI  - Inducible acid tolerance mechanisms in enteric bacteria.
AB  - Enteric micro-organisms have developed several inducible mechanisms for surviving
      transient periods of extreme acid stress. Salmonella typhimurium possesses an
      acid tolerance response (ATR) induced in minimal medium by short exposures to
      mild acid stress. More than 50 acid shock proteins (ASPs) are induced during
      adaptation. Eight ASPs are regulated by the major iron regulatory protein, Fur,
      in an unusual iron-independent manner. The two-component regulator, PhoP, is an
      autoinduced ASP that controls the induction of three additional ASPs. The stress
      sigma factor sigma S is an ASP that regulates induction of eight ASPs. Acid
      induction of sigma S is due to its decreased proteolytic turnover via the ClpXP
      protease in conjunction with the two-component-type response regulator MviA (RssB
      in Escherichia coli). Mutations in any of these three regulators leads to a
      defective ATR. Repair of pH stress-induced DNA damage appears to require the Ada
      protein (O6-methylguanine methyltransferase) since an ada mutant is both acid and
      alkaline sensitive. In contrast to S. typhimurium, E. coli and Shigella have acid
      resistance systems induced in complex media that include a glucose-repressed
      system protective at pH 2.5 without amino acid supplementation, a glutamate
      decarboxylase system that requires glutamate and an arginine decarboxylase system
      unique to E. coli.

PMID- 10207914
TI  - Acid and base regulation in the proteome of Escherichia coli.
AB  - Acid and base conditions have many significant effects on the growth of
      Escherichia coli. External and internal pH perturbations induce different classes
      of genes. pH-dependent regulation of genes intersects with other regulatory
      responses, e.g. oxygen level or osmolarity. 2D electrophoretic gels were used to
      compare global patterns of protein induction in Escherichia coli grown in complex
      media buffered at the acid or alkaline ends of the pH range for growth (pH 4.4
      vs. pH 9.1). Preliminary results indicate new classes of acid- and base-dependent
      regulation, in some cases highly dependent on oxygen level. Other proteins are
      induced strongly at both extremes of pH, compared to pH 7. Current work continues
      to dissect the relationship between effects of pH, oxygen level and osmolarity.

PMID- 10207915
TI  - Acid tolerance induced by metabolites and secreted proteins, and how tolerance
      can be counteracted.
AB  - Several metabolites and salts including glucose, L-glutamate, L-aspartate, FeCl3,
      KCl and L-proline induce acid tolerance at neutral external pH (pHo) in log phase
      Escherichia coli. For induction by glucose and L-glutamate, the processes are
      independent of integration host factor (IHF), H-NS, CysB, ferric uptake regulator
      (Fur) and RelA. For most of the above, tolerance does not appear if induction
      occurs and NaCl, sucrose, SDS or DOC are present. For several responses, cAMP
      inhibits induction. For many established acid tolerance and sensitization
      processes, including those tolerance responses switched on at pH 5.0 and by
      glucose, glutamate or aspartate, induction is associated with secretion of
      extracellular induction proteins. These proteins bring about the response if
      added to organisms under normally non-inducing conditions. Secreted components
      also influence inherent acid tolerances and sensitivities. Analysis of some
      established tolerance responses indicates that induction is a two-stage process,
      secreted extracellular proteins playing an obligate role in induction. For
      example, the functioning of the acid-induced medium protein(s) is essential for
      acid habituation at pHo 5.0. It seems likely that such two-stage mechanisms are
      essential for many inducible processes in bacteria.

PMID- 10207916
TI  - Acid tolerance in root nodule bacteria.
AB  - Biological nitrogen fixation, especially via the legume Rhizobium symbiosis, is
      important for world agriculture. The productivity of legume crops and pastures is
      significantly affected by soil acidity; in some cases it is the prokaryotic
      partner that is pH sensitive. Growth of Rhizobium is adversely affected by low
      pH, especially in the 'acid stress zone'. Rhizobia exhibit an adaptive acid
      tolerance response (ATR) that is influenced by calcium concentration. Using Tn5
      mutagenesis, gusA fusions and 'proteome' analysis, we have identified a range of
      genes that are essential for growth at low pH (such as actA, actP, exoR, actR and
      actS). At least three regulatory systems exist. The two-component sensor
      regulator system, actSR, is essential for induction of the adaptive ATR. Two
      other regulatory circuits exist that are independent of ActR. One system involves
      the low pH-induced regulator gene, phrR, which may control other low pH-regulated
      genes. The other circuit, involving a regulator that is yet unidentified,
      controls the expression of a pH-regulated structural gene (lpiA). We have used pH
      responsive gusA fusions to identify acid-inducible genes (such as lpiA), and then
      attempted to identify the regulators of these genes. The emerging picture is of a
      relatively complex set of systems that respond to external pH.

PMID- 10207917
TI  - How can archaea cope with extreme acidity?
AB  - Archaea are the most extremophilic of the acidophilic microbes, combining, in
      many cases, acidophilicity with hyperthermophilicity. They form one of the three
      branches of the phylogenetic tree, and they are specifically found within the so
      called crenarchaeota, typical members of which thrive at pH 1-3 and at
      temperatures of 75 degrees C to nearly 100 degrees C. Despite this, these cells
      can maintain a near neutral cytosol, and they use H+ for chemiosmotic coupling of
      ADP phosphorylation. These phenomena require efficient exclusion and disposal of
      protons. This is achieved by multiple synergistic mechanisms that act in
      parallel. One strategy is to use bipolar tetraether lipids as a matrix of their
      plasma membranes, providing low ion permeabilities, even at high temperatures.
      Additionally, an inverted membrane potential can help to balance a large pH
      gradient of up to 4 at a proton motive force of delta p = 140-180 mV. This is not
      a general rule, because in several species the membrane potential contributes
      only minimally. Also, local buffering capacity and charge profiles across the
      membrane may significantly influence adaptation to bulk phase acidity. Neither
      complex I nor complex III electron transport-coupled proton pump equivalents have
      been found in aerobic archaea. Only terminal oxidases seem to provide either H+
      pumping or the generation of a proton gradient by chemical charge separation.
      Organization, redox centres and primary structures of some archaeal terminal
      quinol oxidase complexes are known and will be discussed. Much less is known
      about anaerobic sulfur reducers. For those a possible mechanism for proton
      exclusion is proposed.

PMID- 10207918
TI  - pH homeostasis in acidophiles.
AB  - The acidophilic bacteria comprise an environmentally important group that
      includes pathogens. A fundamental requirement for existence in strongly acidic
      environments is generation of a large pH gradient (delta pH) to maintain the
      cytoplasmic pH near neutrality and safeguard the acid-labile cell constituents.
      These organisms require the capacity to extrude H+ across the thermodynamic
      barrier imposed by the delta pH. They also need special transport proteins that
      can function in strongly acidic environments. The quintessential device by which
      the acidophiles fulfil these requirements by generating a positive-inside
      membrane potential (delta psi) that mitigates both the force against which H+
      must be extruded, as well as the influxing force of protons into the cells. The
      delta psi is generated through passive as well as active mechanisms. The former
      constitutes an H+ diffusion as well as a Donnan potential, and the latter
      involves electrogenic circulation of Cl-, and the operation of an electrogenic
      H+/K+ (Na+) antiporter.

PMID- 10207919
TI  - pH tolerance in Bacillus: alkaliphiles versus non-alkaliphiles.
AB  - Monovalent cation/proton antiporters that catalyse electrogenic uptake of H+ in
      exchange for cytoplasmic K+ and/or Na+ are centrally involved in bacterial pH
      homeostasis under alkaline challenge. Systematic attempts have identified some,
      but not yet all, of the genes encoding such antiporters that participate in pH
      homeostasis in the neutrophilic Bacillus subtilis and the extremely alkaliphilic
      Bacillus firmus OF4. In each organism there are at least three distinct
      antiporters involved in pH homeostasis. They differ in cation requirement, with
      pH homeostasis specifically utilizing Na+/H+ antiport in the alkaliphile and
      using either Na+ or K+/H+ antiport in B. subtilis. Some of the antiporters
      involved in pH homeostasis are constitutive and are in place to respond to sudden
      pH shifts, but there is also an inducible component. At least two sets of
      homologous antiporters (NhaC and Mrp/Pha) function in both alkaliphiles and
      neutrophiles. An additional antiporter of a different transport protein family,
      the Gram-positive tetracycline-metal/H+ antiporter, is important in pH
      homeostasis in B. subtilis but has not yet been shown to be present in any
      alkaliphile. There are also differences outside of the antiporters themselves
      that contribute to the greater capacity of the alkaliphiles for pH homeostasis,
      including cation re-entry capacity and possible surface properties.

PMID- 10207920
TI  - The molecular mechanism of regulation of the NhaA Na+/H+ antiporter of
      Escherichia coli, a key transporter in the adaptation to Na+ and H+.
AB  - The NhaA Na+/H+ antiporter is the main system responsible for adaptation to Na+
      and alkaline pH (in the presence of Na+) in Escherichia coli and many other
      enteric bacteria. It is under intricate control. At the protein level it is
      regulated directly by pH, one of its regulatory signals. A pH shift from 7 to 8.5
      activates the antiporter and, in a fashion correlated with the activity change,
      confers a conformation change that, in isolated membrane vesicles, is reflected
      in the exposure of trypsin-cleavable sites. H225 and G338 are essential for the
      pH response of NhaA. nhaA transcription is dependent on NhaR, a positive
      regulator of the LysR family, and is regulated by Na+, the other environmental
      signal. Na+ affects the NhaR/nhaA interaction directly by changing the footprint
      of NhaR on nhaA in a pH-dependent fashion. The expression of nhaA is also under
      global regulation of H-NS. We suggest that the pattern of regulation of nhaA
      found in E. coli is a paradigm for the response of proteins and genes to H+ and
      Na+, the most common ions that challenge every cell.

PMID- 10207922
TI  - Proton ATPases in bacteria: comparison to Escherichia coli F1F0 as the prototype.
AB  - The F1F0 ATP synthase complex of Escherichia coli functions reversibly in
      coupling proton translocation to ATP synthesis or hydrolysis. The structural
      organization and subunit composition corresponds to that seen in many other
      bacteria, i.e. a membrane extrinsic F1 sector with five subunits in an alpha 3
      beta 3 gamma delta epsilon stoichiometry, and a membrane-traversing F0 sector
      with three subunits in an a1b2c12 stoichiometry. The structure of much of the F1
      sector is known from a X-ray diffraction model. During function, The gamma
      subunit is known to rotate within a hexameric ring of alternating alpha and beta
      subunits to promote sequential substrate binding and product release from
      catalytic sites on the three beta subunits. Proton transport through F0 must be
      coupled to this rotation. Subunit c folds in the membrane as a hairpin to two
      alpha helices to generate the proton-binding site in F0. Its structure was
      determined by NMR, and the structure of the c oligomer was deduced by cross
      linking experiments and molecular mechanics calculations. The implications of the
      oligomeric structure of subunit c will be considered and related to the H+/ATP
      pumping ratio, P/O ratios and the cation-binding site in other types of F0. The
      possible limits of the structure in changing the ion-binding specificity,
      stoichiometry and routes of proton entrance/exit to the binding site will be
      considered.

PMID- 10207921
TI  - Bacterial energetics at high pH: what happens to the H+ cycle when the
      extracellular H+ concentration decreases?
AB  - A decrease in the extracellular H+ concentration creates difficulties for
      membrane-linked energetics in bacteria employing H+ as the coupling ion. At high
      extracellular pH (pHo), H+ ions pumped from the cell by, say, the respiratory
      chain, are immediately neutralized by the alkaline extracellular medium. Under
      such conditions, the only driving force that might compel outer H+ ions to return
      to cytosol and perform their function is the electric potential difference across
      the cytoplasmic membrane (delta psi). However, when delta pH in the opposite
      direction is equal to, e.g., 2 pH units (intracellular pH = 7.5 at pHo = 9.5),
      delta psi would be so high that the risk of membrane electric breakdown would
      increase. This is why some bacteria deal with high pH by, for example, replacing
      H+ by Na+ as the coupling ion rather than by increasing delta psi. It has been
      shown in several species of bacteria that the alkalinization of the growth medium
      induces primary Na+ pumps (e.g. Na(+)-motive respiratory chain enzymes and Na+
      ATPase). Electrogenic Na+ efflux via these pumps produces an electrochemical Na+
      potential difference (delta mu Na+) composed of delta psi and delta pNa+. delta
      mu Na+ can be used to perform various types of membrane-linked work. The delta
      psi constituent of delta mu Na+ may maintain electrophoretic influx of H+ such
      that the alkalinization of cytoplasm is prevented. The latter function may be
      supported by a mechanism based on the uphill influx of Cl- instead of Na+. This
      seems to be the case for alkaliphilic and halophilic Natronobacter pharaonis.
      There is an indication that not only Na+ but also Ca2+ may substitute for H+ in
      Gleobacter violaceus growing at high pH.

PMID- 10207923
TI  - Cation movements at alkaline pH in bacteria growing without respiration.
AB  - The respiratory chain has a central role in energy metabolism as a generator of a
      proton motive force in aerobic bacteria. In contrast, Enterococcus hirae
      (formerly Streptococcus faecalis), which lacks the respiratory chain, generates
      this proton gradient via a F-type H+ ATPase, but it works only at a pH below 8;
      no significant proton motive force is generated at a pH above 8. An Escherichia
      coli mutant deficient in both the respiratory chain and the H+ ATPase grew with a
      negligible proton motive force within the wide range of medium pH. It has been
      suggested that both E. hirae and E. coli are able to grow even when the cytoplasm
      is alkalinized beyond pH 8. These observations lead to the conclusion that
      bacteria can survive without operating cation transport systems driven by a
      proton motive force at alkaline pH. The activity of any transport system with
      optimum pH around neutrality should decline when both the outside and inside of
      cells are alkalinized. Thus, changes in transport systems as well as cellular
      metabolism may be essential for bacterial adaptation to changes in environmental
      pH.

PMID- 10207924
TI  - Presurgical evaluation and surgical outcome of temporal lobe epilepsy.
AB  - The authors analyzed 22 patients younger than 18 years of age with temporal lobe
      epilepsy (TLE) treated surgically. Patients underwent a comprehensive presurgical
      evaluation, including video-electroencephalogram. Fifty-five percent had a
      history of febrile seizures. Eighty-two percent had auraes and most exhibited
      oroalimentary and gestural automatisms. Contralateral dystonic posturing was
      present in 36% and postictal dysphasia in 54% of patients with left-sided
      resections. Cranial magnetic resonance imaging (MRI) was abnormal in 59% of
      patients. MRI revealed changes consistent with mesial temporal sclerosis in 8
      (47%) of 17 patients without lesions. Fluorodeoxyglucose-positron emission
      tomography (PET) scans revealed ipsilateral temporal hypometabolism (PET-TH) in
      12 (85.7%) of 14 patients. The intracarotid amobarbital procedure revealed
      impaired memory of the epileptogenic side in 59% of patients. Seventeen patients
      underwent en-bloc resections and five lesionectomies and resection of the
      epileptogenic area. There was no surgical morbidity or mortality. Forty-three
      percent had hippocampal sclerosis, 28.5% gliosis, 14% low-grade tumors, 9.5%
      cavernous angiomas, and 5% had no pathologic findings. Follow-up (6 months to 12
      years) was available for 21 patients; 76% became seizure free, 19% had rare
      seizures, and 5% had a worthwhile improvement. TLE can be safely treated
      surgically in younger patients with excellent results. The clinical
      manifestations were similar to adult patients. PET-TH was present even at a
      younger age, suggesting that the focal functional deficits appear early in
      patients with medically refractory TLE, which may help in the early
      identification of these patients.

PMID- 10207925
TI  - Acetazolamide and furosemide for posthemorrhagic hydrocephalus of the newborn.
AB  - The authors evaluated the efficacy of acetazolamide (ACZ) and furosemide (FUR) in
      avoiding ventricular shunting procedures in preterm infants with posthemorrhagic
      hydrocephalus (PHH) and increased intracranial pressure (ICP). Preterm infants
      were screened for PHH (defined as ventriculomegaly [VM] and increased ICP
      measured with the Ladd fiberoptic monitor). PHH infants were randomized to ACZ
      and FUR treatment or serial lumbar puncture (LP) and monitored until not
      receiving medications or having undergone shunting. Of 69 infants with IVH
      screened for the study, 39 never developed VM, 14 developed VM, without increased
      ICP, and 16 developed PHH. Ten PHH infants were randomized to ACZ and FUR
      treatment and six to serial LP. Nine (90%) of the 10 infants assigned to the ACZ
      and FUR group avoided shunting. Nephrocalcinosis developed in a significant
      proportion of treated infants. Three (50%) of the six LP group infants did not
      require shunting procedures (P = 0.118). The authors conclude that ACZ and FUR
      therapy is useful in the treatment of preterm infants with PHH. Because a
      significant number of infants treated with both ACZ and FUR developed
      nephrocalcinosis, close monitoring for increased calcium excretion in the urine,
      or use of ACZ without FUR, is advised.

PMID- 10207926
TI  - Subclinical hyperthyroidism and hyperkinetic behavior in children.
AB  - The authors report three children who exhibited developmental learning
      disabilities (DLDs) associated with behavioral disturbances, such as attention
      deficit, hyperactivity, and autistic features. The thyroid function tests
      performed as a part of routine endocrinologic evaluation of children with DLDs
      revealed a hormonal profile consistent with hyperthyroidism. These children had
      no systemic signs of hyperthyroidism. Treatment with neomercazole resulted in
      good control of their hyperkinetic behavior and subsequent improvement in
      language function attributable to an increased attention span, thereby
      facilitating speech therapy. Although routine screening of all children with DLDs
      for thyroid dysfunction may not be cost-effective, selective screening of
      children with familial attention-deficit hyperactivity disorder and those with
      attention-deficit and hyperactivity in association with DLDs and pervasive
      developmental disorders appears to be justified.

PMID- 10207927
TI  - Development of two stable oral suspensions for gabapentin.
AB  - Gabapentin is not available in a liquid dosage form for clinical use. This study
      was designed to develop two oral gabapentin suspensions and determine their
      stability under refrigeration or at room temperature. Commercially available
      gabapentin capsules were used to prepare two suspensions: one in extemporaneously
      prepared 1% methylcellulose in syrup (1:1) and another in equal volumes of
      commercially available suspending agents/syrup (Ora Plus/Ora Sweet). Each
      suspension containing gabapentin (100 mg/mL) was stored in 10 plastic
      prescription bottles; five were stored at 4 degrees C and five at 25 degrees C.
      Three 500-microL samples were collected immediately after preparation (day 0) and
      on days 7, 14, 28, 42, 56, 70, and 91. Gabapentin was measured by accurate,
      reproducible, specific, and stability-indicating high-performance liquid
      chromatography (n = 15). The observed mean concentrations exceeded 90% of the
      initial concentrations in both suspensions for 91 days at 4 degrees C and 56 days
      at 25 degrees C. No change in pH, odor, or physical appearance was observed. On
      the basis of these results, stable oral suspensions of gabapentin can be prepared
      and stored in plastic prescription bottles for 91 days at 4 degrees C or 56 days
      at 25 degrees C.

PMID- 10207928
TI  - Brain tumors in childhood and adolescence.
AB  - Brain tumors are the second most common neoplasm in childhood and adolescence.
      With the recent advances in technology, changes in tumor incidence have been
      reported. This study examines this statement. A 19-year retrospective case review
      of primary brain tumors in persons younger than 18 years of age at time of
      diagnosis, who had permanent residence in our catchment area, was performed. Data
      were examined for changes in presenting symptoms and signs and incidence rates
      for tumors on the basis of anatomic location and histologic tumor type. An
      incidence rate of 2.76 per 100,000 people younger than 18 years of age was found.
      During the period of this study a small, but significant, trend toward increasing
      incidence was evident. No changes in patterns of presentation or duration of
      symptoms before diagnosis was observed. The incidence rate based on histologic
      tumor diagnosis remained fairly constant during the study period.

PMID- 10207929
TI  - Prevalence of peripheral neuropathy with insulin-dependent diabetes mellitus.
AB  - Insulin-dependent diabetes mellitus (IDDM) is rare in Chinese children. There
      have been no reports on the prevalence of peripheral neuropathy in Chinese
      children with IDDM. This study aimed to determine prevalence of subclinical
      peripheral neuropathy in Chinese children with IDDM. Motor and sensory nerve
      conduction studies of both median, ulnar, peroneal, and tibial (motor nerves) and
      median, ulnar, and sural (sensory nerves) were performed in 38 children with IDDM
      (18 males, 20 females). The age was 4-21 years (mean = 12.7 years; median = 12
      years, 6 months). The duration of diabetes was less than 5 years in 15, 5-10
      years in 14, and more than 10 years in nine. Neurophysiologic evidence of
      subclinical peripheral neuropathy was present in 26 patients (68.4%) of which
      motor, sensory, or motor and sensory involvement was 26 (68.4%), eight (21.1%),
      and 26 (68.4%), respectively. Twelve (31.6%) and 14 (36.8%) children had mild and
      moderate degrees of peripheral neuropathy, respectively. Among the 26 children
      with abnormal nerve-conduction studies, two (7.7%) had symptoms of numbness and
      pain in the lower limbs. Thus, two children had symptomatic neuropathy and most
      (n = 24) had asymptomatic peripheral neuropathy. Two children had systemic
      hypertension, and one (3.8%) had laboratory evidence of early renal
      complications. Analysis of demographic and laboratory risk factors for the
      development of subclinical peripheral neuropathy revealed that the age of onset,
      duration of diabetes, level of hemoglobin A1c, triglyceride, cholesterol, serum
      creatinine, and urea, microalbumin/creatinine ratio, and urinary microalbumin
      excretion rate were significantly related to the development of subclinical
      peripheral neuropathy in specific nerves.

PMID- 10207930
TI  - Expression of protective protein in human tissue.
AB  - The authors investigated by immunohistochemistry the distribution of protective
      protein in human tissues. Immunoreactivity was observed in the cytoplasm,
      revealing a granular pattern and cell type specificity. The most intense staining
      was observed in the large neurons of brain, distal and collecting tubular cells
      of kidney, epithelial cells of bronchus, and Leydig cells of testis. In a patient
      with galactosialidosis type IIa, all these stains were absent. The neurons that
      were most strongly stained in the control group, such as the Betz cells, neurons
      in the basal forebrain, motor neurons in the cranial nerve nuclei, and ventral
      horn cells of the spinal cord, were markedly ballooned in the patient with
      galactosialidosis.

PMID- 10207931
TI  - The pitfall of silent neurosarcoidosis.
AB  - Sarcoidosis in childhood is seldom reported. Most cases are observed in older
      children and preadolescents as bilateral pulmonary disease and eye lesions.
      Arthritic features are more likely to be observed in infants and children younger
      than 4 years of age who do not develop pulmonary disease. Neurosarcoidosis is
      exceptional in this age group and seldom suspected when the neurologic symptoms
      are present. The authors report a pediatric patient with systemic sarcoidosis who
      developed a severe but silent neurologic involvement. Numerous masslike lesions
      were discovered on systematic cranial magnetic resonance imaging. The authors
      recommend a complete screening of extrapulmonary manifestations in children with
      sarcoidosis. The proper management of patients with incidentally discovered
      neurosarcoidosis has yet to be established.

PMID- 10207932
TI  - Trihexyphenidyl in posthemorrhagic dystonia: motor and language effects.
AB  - Trihexyphenidyl has been found to be an effective treatment for dystonic movement
      disorders, improving gross motor function in patients with axial and torsional
      dystonia, tremors, and myoclonus. In this report, improvements in fine motor
      control, language, and oral motor skills are described with trihexyphenidyl in an
      8-year-old female who developed dystonia after spontaneous bilateral putamenal
      hemorrhages. No adverse side effects occurred. The mechanism of action of
      trihexyphenidyl is believed to be in the basal ganglia where it inhibits
      muscarinic cholinergic receptors and increases the turnover of dopamine.

PMID- 10207933
TI  - Vocal cord paralysis and hypoventilation in a patient with suspected Leigh
      disease.
AB  - The authors report the case of a 16-month-old male with suspected Leigh disease,
      which was diagnosed on the basis of the clinical manifestations, abnormal lactate
      stimulation test, proton magnetic resonance spectroscopy, and neuroradiologic
      findings. Progressive stridor resulting from bilateral vocal cord paralysis and
      hypoventilation was evident. The authors suggest that for infants or children who
      exhibit vocal cord paralysis, mitochondrial disorders, such as Leigh disease,
      should be considered.

PMID- 10207934
TI  - Congenital hypomyelinating neuropathy: two patients with long-term follow-up.
AB  - The authors report the long-term prospective follow-up of two unrelated females
      with congenital hypomyelinating neuropathy (CHN) and review previously reported
      cases. The authors' first patient presented with neonatal hypotonia and extremely
      slow nerve conduction velocities. Sural nerve biopsy revealed profound
      hypomyelination, without inflammation or evidence of myelin breakdown. She is now
      9 years of age, and her motor function has continued to improve. Follow-up nerve
      conduction velocities are unchanged. The authors' second patient presented at 5
      months with hypotonia. Nerve-conduction velocities were extremely slow, and sural
      nerve biopsy revealed severe hypomyelination, with no inflammation or evidence of
      myelin breakdown. She is now 5 years of age and has also demonstrated improved
      motor function. Repeated nerve-conduction velocities are unchanged. Both patients
      have normal cognitive development. Molecular genetic analysis in Patient 2
      disclosed a point mutation in the myelin protein zero gene; this same point
      mutation has been reported in three other patients diagnosed with Dejerine-Sottas
      syndrome (DSS) but has never been reported in a patient with CHN. Although CHN is
      a distinct clinical entity, it may share similar genetic features with DSS.

PMID- 10207935
TI  - Poliomyelitis-like syndrome associated with Epstein-Barr virus infection.
AB  - A 20-month-old male presented with an acute clinical syndrome resembling
      poliomyelitis, characterized by a flaccid monoplegia, areflexia of the involved
      limb, and preserved sensation. Electrophysiologic studies supported a
      neuronopathic localization involving the anterior horn cells. Although laboratory
      evidence for a poliovirus infection was absent, serologic and polymerase chain
      reaction studies documented an active central nervous system infection with
      Epstein-Barr virus, indicating that a poliomyelitis-like syndrome may be produced
      by infectious agents other than enteroviruses.

PMID- 10207936
TI  - Male Rett syndrome variant: application of diagnostic criteria.
AB  - Classic Rett syndrome (RS) has been described in females only. Although an X
      chromosome origin is probable, it has not been substantiated. It is possible,
      therefore, that RS could occur in males. The authors describe a male with RS and
      review all the reported cases involving male patients. The authors compare their
      patient to the other patients and examine the applicability of the classic RS
      diagnostic criteria to this variant. To date, nine male patients with RS have
      been reported. The authors describe an additional male who met seven of nine
      necessary criteria and six of eight supportive criteria as defined by the RS
      Diagnostic Criteria Work Group. When the authors applied these criteria to the
      other nine reported patients, many necessary inclusion criteria were not met
      despite the absence of exclusion criteria. The supportive criteria were even more
      variable and limited in many patients. In conclusion, males with RS appear to
      represent a heterogeneous phenotype, with clinical features that may meet many
      but not all of the necessary diagnostic criteria of classic RS. Less restrictive
      criteria are needed to include this variant, which should be considered when
      evaluating males with idiopathic developmental regression, autistic features, and
      loss of hand function.

PMID- 10207938
TI  - Lung transplantation in sarcoidosis: lessons learned from immunology.

PMID- 10207937
TI  - Posterior leukoencephalopathy syndrome may not be reversible.
AB  - The association of an acute reversible encephalopathy with transient occipital
      lobe abnormalities on imaging studies is well known. This condition has been
      called reversible posterior leukoencephalopathy syndrome. The clinical
      presentation usually includes seizures, headache, altered mental status, and
      blindness, often associated with hypertension and immunosuppressants. The authors
      discuss a two-year-old male with Down syndrome who presented 2 months after
      allogeneic bone marrow transplantation with severe oculogyric crisis, without
      other complaints. The patient was being treated for hypertension and was
      receiving cyclosporine for prophylaxis of graft-vs-host disease. A computed
      tomography scan of the head revealed marked bilateral lucencies mainly involving
      the white matter of the occipital lobes, with a few foci of punctate hemorrhage.
      The condition improved when cyclosporine was discontinued, but an area of
      leukomalacia was identified on follow-up magnetic resonance imaging. To the
      authors' knowledge, oculogyric crisis as a presentation of reversible posterior
      leukoencephalopathy has not been previously described. Recognizing this
      association is important, because patients receiving cyclosporine are often
      receiving other medications that can potentially cause dystonic eye movements,
      possibly leading to a delay in diagnosis and treatment, which can result in an
      irreversible neurologic deficit.

PMID- 10207939
TI  - Cells and cytokines involved in the pathogenesis of sarcoidosis.
AB  - Granulomatous inflammation develops under the regulatory influence of cytokines
      produced by local mononuclear phagocytes, T cells, dendritic cells, fibroblasts,
      and other local cells. In sarcoidosis, granulomatous inflammation is
      characterized by dominant expression of T helper 1 (Th1) cytokines such as IFN
      gamma and interleukin (IL)-2 with low levels of expression of T helper 2 (Th2)
      cytokines such as IL4 and IL5. Recent studies show that the cytokine IL12, the
      most important regulator of Th1 immune responses currently known, is upregulated
      at sites of inflammation in sarcoidosis. In particular, enhanced expression of
      IL12 is seen in sarcoid lung and lymph node, along with dysregulated production
      of IL12 by stimulated and unstimulated sarcoid alveolar macrophages. The known
      dependence of granulomatous inflammation on type 1 cytokines (IFN gamma, IL12) in
      many experimental models of granulomatous disease makes it likely that these
      cytokines function in a similar fashion in the initiation and maintenance of
      granulomatous inflammation in sarcoidosis. Whether these same type 1 cytokines
      drive granulomatous inflammation in patients with extensive fibrocystic lung
      disease remains unknown. TGF beta, a known inhibitor of IL12 and IFN gamma
      production, is produced at higher levels by lung cells from those patients who
      undergo remission of their disease, suggesting that TGF gamma is important in
      downregulating granulomatous inflammation in sarcoidosis. These studies offer new
      insight into the molecular mechanisms of granuloma formation in sarcoidosis and
      provide a framework for developing new therapeutic strategies for the treatment
      of this disease.

PMID- 10207940
TI  - Epithelioid cell granulomatosis of the lung: new insights and concepts.
AB  - Our knowledge on epithelioid cell granulomatosis of the lung has been extended in
      recent years. New entities have been added, like zirconiosis; others like
      tuberculosis, mycobacteriosis and sarcoidosis have gained new interest, because
      molecular techniques allowed new insight into their pathogenesis and a more rapid
      and species-specific diagnosis. Experimental work in addition has added a lot of
      information about the network of cytokines and other inflammatory mediators
      responsible for granuloma formation. However, our knowledge of this network is
      still incomplete. Three types of agents are now known to cause epithelioid cell
      granulomas: infectious organisms (bacteria and fungi), products of plants and
      animals (pollen, sporangia, proteins), and metallic compounds. In addition, there
      is still a group of epithelioid cell granulomatoses with unknown etiology.
      Sarcoidosis, one of these granulomatoses has recently elicited an old
      controversy; by molecular techniques atypical Mycobacteria and Corynebacterium
      acne have been identified in sarcoid granulomas and a link to the etiology of
      sarcoidosis has been proposed. Whether these bacteria induce some cases of
      sarcoidosis by an allergic mechanism, has still to be proven.

PMID- 10207941
TI  - Computed tomography in the assessment of diffuse lung disease.
AB  - Computed tomography (CT) has a significant impact on the evaluation of patients
      suspected of having diffuse lung disease. The technique is based on thin-section
      scans and high-resolution reconstruction. CT interpretation is based on a
      recognition of the main pattern, associated findings, and distribution of the
      lesions assessed at the regional level as well as the level of the secondary
      pulmonary lobule. CT may demonstrate clinically suspected abnormalities
      undetected on the radiographs. It may have characteristic pictures in patients
      with non specific findings on the radiograph. It can be used to limit the
      differential diagnosis to a few possibilities. In selected cases, in the presence
      of the appropriate clinical setting, CT appearances can be diagnostic or so
      strongly suggestive that lung biopsy can be avoided. When a lung biopsy is
      indicated, CT has a considerable value in determining the most appropriate site
      for the biopsy. To a certain extent, CT may also provide information on disease
      activity and prognosis, particularly in the differentiation between inflammatory
      changes, potentially treatable or reversible, and irreversible lung fibrosis.

PMID- 10207942
TI  - Overexpression of transforming growth factor-alpha and epidermal growth factor
      receptor in idiopathic pulmonary fibrosis.
AB  - BACKGROUND AND AIM: A recent transgenic mouse model overexpressing transforming
      growth factor alpha (TGF-alpha) led to a phenotype of pulmonary fibrosis. In
      order to validate this mouse as a model for idiopathic pulmonary fibrosis in
      humans, we studied the expression of TGF-alpha in lung tissue of patients with
      idiopathic pulmonary fibrosis compared to control lung tissue. METHODS: Tissue
      from both groups was obtained from operative specimens and immediately formalin
      fixed and paraffin embedded. Contiguous four micron sections were prepared for
      conventional histochemical staining and staining with antibodies to either TGF
      alpha or the epidermal growth factor-receptor (EGF-R). Immunostaining was
      performed using the Ventana ES automated immunohistochemistry system. Four cell
      types were examined (vascular endothelium, bronchial epithelium, type 2
      pneumocytes, and fibroblasts) and stain activity was scored on a six point scale.
      RESULTS: Eleven patients with IPF were compared to seven control subjects. TGF
      alpha immunoreactivity was significantly higher in the IPF patients than in
      controls in the vascular endothelium, type 2 pneumocytes, and fibroblasts (P <
      0.005). [IPF (4(2-4) Median (Range)) than the controls (0.5(0-2), p < 0.0005).]
      The differences in EGF-R, one of the receptors for TGF-alpha, between these two
      patient populations were not as striking. There was a small but significantly
      greater expression of EGF-R in the bronchial epithelium and type 2 pneumocytes of
      the IPF patients. CONCLUSIONS: TGF-alpha is overexpressed in patients with IPF,
      especially in the vascular endothelial cells.

PMID- 10207943
TI  - Ultrastructural studies on the formation and distribution of lipid droplets in
      the lung capillary endothelial cells in patients with sarcoidosis.
AB  - BACKGROUND AND AIM OF THE WORK: We previously reported the presence of definite
      morphological alterations in the capillary endothelium of sarcoid lung. The aim
      of this study was to examine ultrastructural changes and distribution of lipid
      droplets in the endothelium of lung capillaries of patients with sarcoidosis.
      METHODS: Tissue specimens were obtained by transbronchial lung biopsy or open
      lung biopsy from 16 patients with sarcoidosis and 13 controls. Biopsies were
      evaluated by electron microscopy following lead citrate and uranyl acetate
      staining. RESULTS: Typical lipid droplets were observed in pulmonary capillaries
      of 11 out of 16 sarcoid patients (69%); the droplet frequency was higher in
      sarcoid patients than in control specimens. Lipid droplets were characterized by
      biphasic density: most droplets contained eccentrically located vacuoles
      (saturated fatty acids) others were characterized by low density areas
      (unsaturated fatty acids). Biphasic droplets were covered by large lysosomal
      granules and were mainly distributed in the endothelium and pericytes.
      Interestingly, in the latter, vacuoles increased in size while small amounts of
      lysosomal granules were detectable. CONCLUSION: Our findings suggest that
      biphasic droplets increase in number in pulmonary capillaries of patients with
      sarcoidosis with a characteristic distribution pattern from the endothelium to
      pericytes.

PMID- 10207944
TI  - Angiotensin II receptor on BALF macrophages from Japanese patients with active
      sarcoidosis.
AB  - BACKGROUND: Serum angiotensin converting enzyme (ACE) activity and its changes
      are important markers for disease activity in patients with sarcoidosis. We
      earlier reported that ACE and its enzymatic product, angiotensin II (A-II), might
      play a role in maintaining macrophage/T lymphocyte alveolitis by enhancing an
      accessory function of macrophages in chronic active cases with sarcoidosis. AIM
      OF THE WORK AND METHODS: We examined whether A-II receptor is present on BALF
      macrophages by a receptor binding assay using 125I-labeled A-II, and by
      amplification of A-II receptor gene transcripts using RT-PCR methods and
      quantification of the amounts of transcripts by HPLC. RESULTS: The receptor
      binding assay suggested that specific binding of A-II to BALF macrophages was
      somewhat more prevalent in active sarcoidosis than in controls. A specific band
      for A-II receptor was detected by RT-PCR. A-II receptor gene expression was
      standardized as the ratio to beta-actin. An increased ratio was shown in active
      sarcoidosis (0.70 +/- 0.19; n = 14) compared to inactive cases (0.14 +/- 0.06; n
      = 5; p = 0.023) and healthy subjects (0.15 +/- 0.09; n = 5, p = 0.029). The ratio
      correlated positively with the percentage of BALF T lymphocytes (r = 0.60, p =
      0.0056), and negatively with BALF macrophages (r = 0.60, p = 0.0055). No
      difference was detected between nonsmokers and smokers. CONCLUSION: The amounts
      of A-II receptor gene expression of BALF macrophages correlated with disease
      activity in patients with pulmonary sarcoidosis.

PMID- 10207945
TI  - Defining organ involvement in sarcoidosis: the ACCESS proposed instrument. ACCESS
      Research Group. A Case Control Etiologic Study of Sarcoidosis.
AB  - BACKGROUND: Sarcoidosis is a multiorgan granulomatous disease of unknown cause.
      Lack of an objective system for assessment of sarcoidosis to evaluate disease
      course and effectiveness of therapy is a major problem. METHODS: The sarcoidosis
      assessment instrument was developed by the Steering Committee of A Case Control
      Etiologic Study of Sarcoidosis (ACCESS) which included investigators at the ten
      ACCESS Clinical Centers, the Clinical Coordinating Center, and representatives of
      the National Heart, Blood, and Lung Institute. This system was developed to
      assess sarcoidosis organ involvement in ACCESS patients who would be followed
      over a two-year period. The system represents a consensus of opinions of members
      of the Steering Committee based on review of their experience and the medical
      literature. RESULTS: Criteria for involvement in patients with biopsy-confirmed
      sarcoidosis are presented for organs and systems that are commonly involved
      (lung, skin, eyes, liver, calcium metabolism), unusual but clinically important
      (nervous system, kidney, heart) and other sites (non-thoracic lymph nodes, bone
      marrow, spleen, bone/joint, ear/nose/throat, parotid/salivary glands, muscles).
      CONCLUSION: The proposed instrument is partially subjective in that it depends
      upon the clinician's diligence in pursuing evidence for sarcoidosis involvement
      of various organs. It is hoped that this instrument will lead to increased
      standardization in the definition of sarcoidosis organ involvement to help
      clinicians and researchers better characterize patients with sarcoidosis.

PMID- 10207946
TI  - Efficacy of azathioprine as second-line treatment in pulmonary sarcoidosis.
AB  - BACKGROUND AND AIM OF WORK: Immunosuppressives such as azathioprine are
      occasionally used in sarcoidosis where corticosteroids cannot be used because of
      poor response, contraindications or unacceptable side effects. The aim of this
      study was to assess the efficacy and safety of azathioprine in the treatment of
      pulmonary sarcoidosis. METHODS: A retrospective study was performed on patients
      in the Respiratory Clinic of the university teaching hospital on all biopsy
      proven sarcoid treated with azathioprine between 1969 and 1993 (n = 10). All had
      previously shown only partial (n = 6) or no (n = 4) response to high dose oral
      corticosteroids. Azathioprine in a dose of 100-150 mg was administered daily,
      while continuing a small dose of oral corticosteroid. Patients underwent regular
      clinical evaluation, pulmonary function testing and chest radiography. RESULTS:
      In one patient the course was too brief to evaluate (26 days). Two patients had
      significant and sustained improvement in lung function (vital capacity increasing
      from 72% to 89% and from 49% to 79% of predicted respectively, and transfer
      factor from 78% to 114% and from 27% to 49% of predicted respectively), and chest
      radiograph cleared. Two patients had short-lived improvement and steroid-sparing
      effect. In the remainder (n = 5), no benefit was observed. No patient responded
      to azathioprine who had failed to respond to high dose corticosteroids. There was
      no significant toxicity. CONCLUSIONS: Azathioprine may provide a safe alternative
      to corticosteroids when a steroid-sparing effect is required, but it is unlikely
      to be effective in patients who fail to respond to high dose corticosteroids
      and/or have radiographic evidence of significant fibrosis.

PMID- 10207947
TI  - Lung transplantation for end-stage pulmonary sarcoidosis.
AB  - BACKGROUND: Sarcoidosis is a multi-system granulomatous disease which can cause
      significant pulmonary morbidity and occasionally be fatal. The long term benefit
      of lung transplantation for this disorder are unknown. METHODS: A retrospective
      review was made of nine single lung transplant procedures performed at the
      University of Pittsburgh between March 1991 and March 1995 in patients with end
      stage lung disease secondary to sarcoidosis. Two contemporaneous groups of
      recipients receiving transplants for COPD (n = 30) and inflammatory lung disease
      (n = 13) served as control groups. Surviving recipients underwent sequential
      surveillance bronchoscopy with transbronchial biopsy. RESULTS: All recipients
      survived beyond post-operative day (POD) 30, with 5 recipients currently alive.
      One year survival for this group was 6/9 (67%). Eight of the 9 sarcoidosis
      recipients had sequential lung biopsy procedures. Five of these 8 recipients
      (62.5%) had recurrence of granulomata in the lung allograft with the mean time to
      diagnosis of recurrent sarcoidosis being POD 224.2 +/- 291.3 (range POD 21-719).
      None of these 5 recipients had radiographic evidence or clinical symptoms related
      to granulomatous inflammation in the allograft. Pre-operative and post-operative
      spirometric values were available on 8 recipients. Vital capacity significantly
      improved in all recipients from 1.54 +/- 0.43 litres to 2.55 +/- 0.63 litres by
      POD 180 and was maintained through the fourth postoperative year (p < 0.05
      Wilcoxon Signed Rank). Spirometric values were also compared before and after
      transplantation in the 5 recipients with granulomata in the allograft. Vital
      capacity significantly improved in these 5 recipients from 1.53 +/- 0.48 litres
      to 2.71 +/- 0.71 litres by POD 180 and was maintained throughout the first
      postoperative year (p < 0.05, Wilcoxon Signed Rank). The prevalence of high grade
      acute cellular rejection [ACR (histologic grades III and IV)] did not differ from
      that seen in a contemporaneous group of 30 single lung recipients who received
      allografts for COPD (p < 0.05 Mann-Whitney U), nor when compared to a group of 13
      single lung recipients who received allografts for immunologically mediated lung
      disease (p < 0.05 Mann-Whitney U). The prevalence of chronic rejection
      (histologic obliterative bronchiolitis [OB]) in the sarcoidosis recipients was
      4/8 (50%). In the controls with COPD recipients the prevalence of OB was 10/30
      (33.3%), and in the 13 controls with immunologic disease it was 6/13 (46.2%).
      There was no significant difference in the prevalence of OB between the
      sarcoidosis recipients and controls. When analyzed to the fifth year after
      transplantation, freedom from the development of OB also failed to differ between
      these 3 groups (p = 0.25, Logrank, Mantel-Cox). CONCLUSIONS: Although
      granulomatous inflammation in the lung allograft is common following
      transplantation for sarcoidosis, it is not clinically or radiographically
      relevant. In addition, the prevalence of high grade ACR and histologic OB is no
      different when compared to other single lung recipients. For these reasons lung
      transplantation is a viable alternative for end-stage lung disease secondary to
      sarcoidosis.

PMID- 10207948
TI  - Association between chronic lymphocytic leukemia and sarcoidosis: clinical value
      of bronchoalveolar lavage.
AB  - We report a case of sarcoidosis, occurred in a patient with chronic lymphocytic
      leukemia (CLL) shortly following the completion of initial chemotherapy, who
      relapsed shortly after a second course. Since bronchoalveolar lavage (BAL)
      demonstrated a predominance of CD4+ lymphocytes, it largely excluded spread of
      the malignant disorder to the lung, and strongly suggested that sarcoidosis was
      the cause of the pulmonary infiltrates. This diagnosis was confirmed by the
      finding of non-caseating granuloma on transbronchial lung biopsy.

PMID- 10207949
TI  - Facial palsy in a patient with leptospirosis: causal or accidental.
AB  - Facial palsy, one of the most common neurological syndromes, has many causes.
      This is the first report of a patient with leptospirosis who developed facial
      palsy. The lesion responded to treatment with doxycycline hyclate.

PMID- 10207950
TI  - How common is sarcoidosis?

PMID- 10207951
TI  - Association of heterozygote glucose-6-phosphate-dehydrogenase deficiency with
      more advanced disease in sarcoidosis.

PMID- 10207952
TI  - An efficient, adaptive method of measuring loudness growth functions.
AB  - This paper presents a new categorical loudness scaling procedure that differs
      from previously published loudness scaling procedures by (i) adaptively selecting
      a new set of levels for each new sequence, (ii) deriving levels that are
      equispaced on the loudness scale, and (iii) using a continuous scale with few
      labels. A major advantage of the adaptive procedure is that the individual
      dynamic range need not be measured prior to loudness testing. The adaptive
      procedure proved to be time efficient and to produce complete loudness functions
      from Not heard to Uncomfortably loud for normal hearing and hearing impaired
      subjects. The pattern of short-term and long-term reliability was similar to that
      reported for non-adaptive loudness scaling procedures. Three presentations
      produced a stable loudness function. Normative curves for one octave babble-noise
      at six test frequencies are presented and compared to normative data obtained
      with a selection of published categorical scaling procedures.

PMID- 10207953
TI  - Measures of the binaural interaction component in human auditory brainstem
      response using objective detection criteria.
AB  - The occurrence of binaural interaction in humans has been demonstrated using
      auditory brainstem response (ABR). A distinctly binaural potential, beta, is
      derived by subtracting the ABR recording evoked by binaural clicks from the
      monaural aggregate, i.e., the sum of the two corresponding ABR recordings evoked
      by monaural clicks. However, few clinical data are available, possibly because
      the beta-wave is considered an elusive response due to a low signal-to-noise
      ratio. In the present study, beta-wave latency, amplitude and area were evaluated
      for 10 subjects with normal hearing using automatic analysis and averaging based
      on a large number of stimulations. The efficacy of the beta-wave measures was
      assessed using different stimulus rates, as binaural interaction is known to
      decrease with increasing stimulus rate. It was found that the beta-wave given by
      automatic analysis demonstrated known characteristics of binaural interaction in
      human ABR, i.e. the absence of binaural interaction during wave III, significant
      binaural interaction during wave V and a significant decrease in binaural
      interaction when the stimulus rate was increased. These findings suggest that a
      beta-wave in the binaural difference waveform can be detected and quantified
      using automatic analysis, thus it is suitable for clinical studies, at least for
      patients with normal hearing thresholds.

PMID- 10207954
TI  - Control of hearing-aid saturated sound pressure level by frequency-shaped output
      compression limiting.
AB  - To fit a hearing aid successfully, it is important to set the Saturated Sound
      Pressure Level (SSPL) or Maximum Power Output (MPO) appropriately. The SSPL
      should be low enough to prevent sounds from being amplified to uncomfortable
      loudness, and yet high enough to maximize speech intelligibility and signal
      quality. To help attain an optimum SSPL setting, a novel output compression
      limiting scheme, with shapable MPO (ShaMPO), has been devised. In ShaMPO, the
      SSPL is shaped across frequencies in accordance with the individual user's
      loudness discomfort levels (LDLs). The contributions of different frequency
      regions to loudness are controlled by summing the amplified signal power relative
      to the LDLs across frequencies, and using this signal to control a wideband
      compressor. This scheme and a conventional output compression limiting (AGCo)
      scheme have been implemented in a digital hearing aid. Ten subjects, with
      moderately-severe to profound sensorineural hearing losses, participated in a
      study comparing speech intelligibility and listening comfort for the two schemes.
      Results showed that there were no significant differences in the speech
      perception scores between AGCo and ShaMPO, even when the speech was presented at
      80 dBA, at which level both schemes were in compression much of the time.
      However, an examination of how subjects selected the SSPL for the two schemes
      revealed that, in many instances, AGCo would permit some sounds with compact
      spectra to be amplified above LDL, whereas ShaMPO would not. Thus the ShaMPO
      scheme can improve listening comfort for some intense sounds without a loss of
      speech intelligibility. In contrast, half the subjects found speech at 80 dBA to
      be uncomfortably loud when listening through their own aids.

PMID- 10207955
TI  - Prevalence of hereditary hearing impairment in adults.
AB  - This contribution, part of an EU-Concerted Action on the genetics of hearing
      impairment (H.E.A.R.), describes the preliminary estimated prevalence of
      hereditary hearing impairment based on retrospective data from a clinical series.
      Of 27,692 subjects examined in the period 1987-91, we sampled 1265 suffering from
      unilateral or bilateral hereditary hearing impairment, which is roughly 5% of
      those examined (n = 384 (31%) male; n = 881 (69%) female). Median age of the
      subjects is 70 years (range 22-98). Subdividing them into 10-year birth cohorts
      and applying the local annual population statistics, the prevalence of an overall
      age-related hereditary hearing impairment was roughly estimated to be 3.2/1000,
      reflecting prevalences as a function of age from 0.8 to 9.4/1000--prevalence in
      females being significantly more than in males (4.1/1000 and 2.1/1000,
      respectively). Overall, a moderate hearing impairment of median 51 dB in the
      better hearing ear was found, averaged across 0.5-4 kHz, this being fairly
      constant up to the age of 60, when a significant reduction in hearing sensitivity
      developed. No significant differences are present as a function of gender, except
      for the birth cohorts 1910-19 and 1920-29. The most frequent type of hereditary
      hearing impairment in this sample is otosclerosis, comprising 2% of the total
      clinical series with a rough population prevalence estimate of 1.4/1000. It is
      concluded that the established database may be of importance in the aggregation
      of very rare diseases, and for providing the inspiration for future prospective
      population studies, resulting in knowledge on the epidemiology of hereditary
      hearing impairment in adults.

PMID- 10207956
TI  - The parents' view on hearing screening in newborns. Feelings, thoughts and
      opinions on otoacoustic emissions screening.
AB  - Since September 1995, universal hearing screening of newborns has been carried
      out at the Linkoping University Hospital with the aid of otoacoustic emissions.
      The present study is based on interviews with parents in order to get their views
      on neonatal hearing screening. A total of 49 persons participated in the
      interviews, the parents of 26 children. A clearly positive attitude to the test
      was expressed by a majority of parents, and the screening seemed to cause very
      little anxiety. Parents whose child passed directly, or after one re-test, were
      very positive to hearing screening. The few parents whose children had to be
      tested more than twice took a more ambivalent view. Anxiety was evoked when the
      child did not pass the first retest; this was a critical point. Another important
      point was when parents finally were given a definite answer as to whether the
      child had a hearing impairment or not; the anxiety then seemed to fade. These
      parents need individual counselling and support during the time of audiological
      assessment, and a plan for future action. From the parents' perspective the
      advantage of hearing screening is the potential to help and understand their
      child at the earliest possible time if a hearing impairment is detected.

PMID- 10207957
TI  - Static magnetic field and the inner ear. A functional study of hearing and
      vestibular function in man after exposure to a static magnetic field.
AB  - The sensory cells of the inner ear are vulnerable to several agents
      (aminoglycosides, cytostatics, ionizing irradiation). The effect of strong
      magnetic fields occurring in industries with production based on electrolytic
      processes and with medical magnetic resonance equipment is unknown. The aim of
      this study was to clarify the effect of strong static magnetic fields on the
      inner ear, by exposing 11 healthy men to a magnetic field with flux density of 2
      7 mT for 9 h. No damage was found to the acoustic or vestibular system.

PMID- 10207958
TI  - Effect of coenzyme Q10 on superoxide production in rats with reperfusion
      injuries.
AB  - We examined the effect of coenzyme Q10 (Co Q10) on superoxide radical (O2-)
      production in a model of rat reperfusion injury. The chemiluminescence method
      using a derivative of luciferin was used to quantify O2- production by
      erythrocytes in the reperfused limb after a period of ischaemia. A total of 20
      limbs from Lewis rats were preserved at 4 degrees C in Euro-Collins solution for
      72 hours, and were grafted orthotopically to syngeneic rats by a microsurgical
      technique. In the treated group (n = 10), Co Q10 (10 mg/kg) was injected
      intraperitoneally into the recipients one hour before reperfusion. In the control
      group (n = 10), the same dose of solvent was given. To measure the extent of
      oxidative stress, heparinised blood from the treated and control recipients was
      collected before, and at 15, 30, and 60 minutes after reperfusion for the
      measurement of chemiluminescence. O2- production in the Co Q10-treated group was
      significantly lower than in the control group (p < 0.05). Although these findings
      suggest that Co Q10 scavenged O2- that was produced in the replanted limbs as a
      result of ischaemia-reperfusion injury, we should consider other possible
      mechanisms by which this agent may protect against ischaemia-induced reperfusion
      injury.

PMID- 10207959
TI  - Adequate blood flow is essential for reinnervation in neurovascular skin flaps.
AB  - The effect of arterial and venous ischaemia on reinnervation of skin flaps after
      transsection and resuture of the epigastric nerve was investigated in rat groin
      flaps. The results were compared with those in corresponding flaps with adequate
      blood flow. Arterial or venous ischaemia was induced by ligation of the
      epigastric artery or vein. The reinnervation of the flaps was studied after a 20
      week healing period using specific antisera for calcitonin gene-related peptide
      (CGRP) in sensory nerves, and neuropeptide Y (NPY) in adrenergic nerves. Arterial
      ischaemia clearly and significantly hampered reinnervation. Venous ischaemia was
      even more harmful and practically no regenerated nerves were detected in the
      flaps. We conclude that adequate blood flow is critical for sensory and
      adrenergic reinnervation in skin flaps.

PMID- 10207960
TI  - A new amorphous hydrocolloid for the treatment of pressure sores: a randomised
      controlled study.
AB  - A randomised controlled study was carried out to compare the effect of a new
      amorphous hydrocolloid (hydrogel, Coloplast) with that of conventional treatment
      on the healing time of pressure sores. After initial debridement in the
      outpatient clinic of pressure sores located in the sacral (n = 21) or
      trochanteric (n = 11) area the patients were randomised to be treated with either
      hydrogel (n = 17) or wet saline compresses (n = 15). Once a week the healing was
      estimated by the same investigator. The relative volumes (from the initial 100%)
      of hydrogel-treated wounds were significantly less (26 +/- 20%, p < 0.02) than
      those of saline treated wounds (64 +/- 16%) in the last week of the study. The
      saline treated wounds needed more frequent weekly debridement than the hydrogel
      treated wounds (21% compared with 7% of all weekly dressings, p < 0.03). We
      conclude that amorphous hydrocolloid increases current healing of pressure sores
      compared with conventional treatment. It is therefore a better choice for
      treating patients with pressure sores in their homes.

PMID- 10207961
TI  - Muscle flap reconstruction for the treatment of major sternal wound infections
      after cardiac surgery: a 10-year analysis.
AB  - Infection of a median sternotomy wound is a rare though potentially fatal
      complication. Despite early diagnosis and proper treatment, prognosis is poor
      because of the chance of mediastinal spread of the infection and the poor
      physical state of these patients. Muscle repair is superior to more conservative
      surgical options such as sternal resuturing with mediastinal irrigation. During
      the last 10 years, complications--including sternal infections and dehiscences-
      have been encountered in 172/4725 median sternotomy wounds after cardiac surgery
      procedures (4%). Thirty-four patients (of whom 30 had acute sternal infections
      and four chronical sternal infections) underwent aggressive sternal debridement
      followed by muscle flap closure. Seventy-two muscle flaps were carried out, a
      pectoralis major bilateral muscle flap being the most common either alone or in
      combination with a rectus abdominis muscle flap. Five perioperative deaths (15%)
      were recorded. Of the 29 surviving patients, 25 patients (74%) were free of
      infection and four (12%) developed recurrence of the infection after a mean
      follow up of 3 years (range 49 days-8 years). We conclude that although muscle
      repair is not free of complications, it is reliable in reducing mediastinitis
      related morbidity and mortality.

PMID- 10207962
TI  - Transposition of the great omentum for infected sternotomy wounds in cardiac
      surgery. Report of 16 cases and review of published reports.
AB  - The expanding indications for coronary artery bypass graft (CABG) and cardiac
      valves replacement have caused an increase in the number of sternal infections.
      The common treatment includes appropriate antibiotics, early debridement, and
      transposition of muscle flaps with or without skin grafts. When other treatments
      have proved unsatisfactory, we have used the great omentum for wound closure.
      During the last five years, 16 patients (10 women, six men, median age 63 years)
      underwent repair of infected sternotomy wounds by the transposition of the great
      omentum, after failure of pectoralis major or rectus abdominis muscle flaps (n =
      9). Seven patients underwent transposition of the great omentum as the first
      choice. The omentum covers the sternal defect well and the closure was reliable.

PMID- 10207964
TI  - Free peroneal skin flap for oropharyngeal reconstruction.
AB  - The thicknesses of three dermal flaps, platysma, forearm, and fibula, which are
      often used for oropharyngeal reconstruction, were measured in 21 subjects using
      15 MHz Doppler ultrasonography. The mean (SD) thicknesses were 2.2 (0.3), 3.1
      (0.5), and 3.8 (0.6) mm, respectively. The free peroneal skin flap from the leg
      was used in 14 patients with head and neck cancer. These flaps were successfully
      transplanted in 13 of 14 patients (93%) with no problems at the donor site. This
      flap offers many advantages, including its distance from the head and neck, its
      cosmetic superiority to a forearm flap, it allows two flaps with two cutaneous
      branches, it is possible to close the donor site primarily without a skin graft,
      and it has thin subcutaneous tissue. We found that the free peroneal skin flap is
      particularly useful for oropharyngeal reconstruction.

PMID- 10207963
TI  - One-stage reconstruction of defects in the hypopharyngeal region with free flaps.
AB  - Despite the almost universal poor prognosis, the reconstruction of combined
      cervical skin and hypopharyngeal defects after extensive resection of tumour
      should maintain optimal quality of life. From 1992 to 1996 we treated 10 patients
      with combined skin and hypopharyngeal defects with five fasciocutaneous free
      flaps, three myocutaneous latissimus dorsi free flaps, one myocutaneous VRAM
      (vertical rectus abdominis muscle) free flap and one free radial forearm flap.
      None of our flaps failed. The complications that required revision (one arterial
      bleeding, one arterial thrombosis, two fistula formations, one superficial wound
      dehiscence, one haematoma) occurred mainly in those patients having secondary
      reconstructions. After primary extensive oncological resection of these tumours
      reconstruction should be done in one stage. The primary reconstruction should
      provide sufficient pharyngeal lining, a satisfactory covering of cervical soft
      tissue, and adequate functional rehabilitation. We have reviewed our experience
      and conclusions about the advantages, disadvantages, and current indications for
      different free flaps in the reconstruction of combined hypopharyngeal, cervico
      oesophageal, and cervical skin defects.

PMID- 10207965
TI  - Evaluation of muscle graft using facial nerve on the affected side as a motor
      source in the treatment of facial paralysis.
AB  - To acquire symmetry of the cheek when smiling, we carried out 39 free
      vascularised grafts of the muscle, the motor nerve of which was sutured to a
      stump of the ipsilateral facial nerve, for 39 patients with facial paralysis. We
      used two methods: an as healthy and fresh as possible facial nerve stump (method
      1A, n = 17), or an incompletely affected stump (method 1B, n = 22). The results
      are classified into grade 1 to 5 indicating increasing efficiency of muscle
      function. All patients who had method 1A and 14 patients who had method 1B were
      evaluated grade 4 or better. Both an incompletely affected facial nerve stump and
      the proximal stump of a facial nerve that had previously been resected have
      sufficient function to provide contraction in the grafted muscle.

PMID- 10207967
TI  - Treatment of sleep apnoea with continuous positive airway pressure in children
      with craniofacial malformations.
AB  - We conducted sleep studies in a consecutive series of 21 children with
      craniofacial malformations and suspected obstructive sleep apnoea. Thirteen had
      sleep apnoea, and one patient with a tracheostomy could not be tested. Twelve
      children were admitted for initiation of treatment with nasal continuous positive
      airway pressure (nCPAP). Ten patients accepted nCPAP, two did not. Seven children
      use home treatment successfully. Obstructive sleep apnoea in most children is
      completely eliminated with nCPAP. The treatment is safe, effective, and leads to
      a reduction in the number of operations done for children with craniofacial
      malformations. Aesthetic operations can be delayed until facial growth is
      complete.

PMID- 10207966
TI  - Reference values of facial features in Scandinavian children measured with a
      range-camera technique.
AB  - Reference values of facial features in white Scandinavian children were
      ascertained using a newly developed range-camera technique with a three
      dimensional measuring program specifically designed for anthropometric
      measurements. Seven facial features in 613 healthy subjects (322 girls, 291
      boys), aged 1 month to 18 years, and nine subjects with the fetal alcohol
      syndrome,aged 7 to 18 years, were studied. Data were analysed by multivariate
      multiple regression and measurements of each facial feature plotted against age
      and presented as curves, with 95% and 99% univariate prediction limits. All
      children with fetal alcohol syndrome had shorter palpebral fissures, and in six
      of them the outer canthal distance was shorter than that in the reference group.
      The reference values presented may be useful in clinical practice--for example,
      in the evaluation of children with syndromes that result in dysmorphology of the
      face and in the planning of plastic and reconstructive surgery.

PMID- 10207969
TI  - Bilateral infraorbital nerve block is superior to peri-incisional infiltration
      for analgesia after repair of cleft lip.
AB  - Cleft lip repair is a common operation in infants and requires that the child is
      pain-free during the postoperative period so that handling does not affect the
      integrity of the delicate surgical site. This study was designed to compare the
      efficacy and duration of effect of 0.125% bupivacaine given preoperatively as a
      bilateral infraorbital nerve block with peri-incisional infiltration of the same
      local anaesthetic for postoperative analgesia in cleft lip repair. It was a
      randomised, double blind, prospective study in 30 children aged 4-20 months (ASA
      grade 1). After a standard induction, group A (n = 15) were given a bilateral
      infraorbital nerve block with 0.125% bupivacaine and group B (n = 15) had peri
      incisional infiltration with the same solution. No additional systemic analgesics
      were given before or during the operation. Intraoperative monitoring comprised
      measurement of heart rate and blood pressure and post-operatively pain relief was
      recorded using a behavioural pain relief score. The heart rate, respiratory rate,
      and blood pressure were also monitored at 0, 1, 2, 4, 8, and 24 hours after
      tracheal extubation. The results showed that group A had significantly better
      pain relief (higher scores) than group B for eight hours postoperatively (p <
      0.05). The analgesic requirement in group B became significant at two hours
      postoperatively, while group A had significant analgesic requirements only after
      eight hours. The significant rise in heart rate and blood pressure that
      accompanied tracheal intubation in both groups suggested that while both methods
      of analgesia may be adequate to prevent responses to skin incision, they do not
      substitute for adequate systemic analgesia during the operation. We conclude that
      infraorbital nerve block with 0.125% bupivacaine provides better and more
      prolonged analgesia than peri-incisional infiltration in cleft lip repair.

PMID- 10207968
TI  - Comparisons of facial growth in patients with unilateral cleft lip and palate
      treated by different regimens for two-stage palatal repair.
AB  - The aim of this study was to compare facial development, particularly growth of
      the maxilla, of two groups of patients with unilateral cleft lip and palate in
      whom palatal surgery had been done slightly differently, particularly the timing
      of the procedures. Two-stage palatal repair had been used at 8 (velar closure)
      and 102 months (hard palate surgery) at one cleft centre and at 20 and 62 months
      at another centre. Lateral roentgencephalograms were used to analyse the first
      sample of 20 patients, who were followed longitudinally from 7-16 years of age.
      The other group comprised 17 subjects in the same age range, who were
      investigated cross-sectionally, also by cephalometry. Generally, the outcome of
      the two surgical regimens was similar and equally satisfactory, with no evident
      difference in facial or maxillary morphology between the two samples. From the
      midfacial growth point of view, it might be questioned whether it is necessary to
      delay closure of the cleft in the hard palate until the mixed dentition stage as
      was done at the first cleft centre.

PMID- 10207970
TI  - Pain-free intralesional injection of triamcinolone for the treatment of keloid.
AB  - Intralesional injection of triamcinolone acetonide (TA) for the treatment of
      keloid is painful, and lidocaine-mixed preparations are much the same. I have
      injected TA (10 mg/ml) at the speed of 3-6 ml/hour using an electric syringe pump
      40 times for the treatment of 10 keloids, 18 times without lidocaine and 22 times
      with lidocaine. The 95% confidence intervals (CI) of the 100 mm visual analogue
      pain scale of the TA alone group and the lidocaine-mixed group were 2.0 to 9.5 mm
      and 1.0 to 6.7 mm respectively, suggesting that both are practically pain-free.
      The speed of injection is an important determinant of pain in intralesional
      chemotherapy. The injection should be extremely slow and lidocaine should be
      added for sensitive patients.

PMID- 10207971
TI  - Vibrotactilometry as a diagnostic tool in ulnar nerve entrapment at the elbow.
AB  - Vibrotactilometry with testing of the thresholds of the vibration sense at seven
      frequencies between 8-500 Hz in different intensities has been correlated with
      nerve conduction studies of the ulnar nerve to evaluate its diagnostic power in
      neuropathies at the elbow. Thirty-nine patients with entrapment symptoms were
      studied. Vibrotactilometry was abnormal in 33 patients (85%) and nerve conduction
      studies were abnormal in 19 (49%). The sensitivity of vibrotactilometry in
      relation to nerve conduction studies was 89%, and in relation to the patients'
      symptoms was 85%. We conclude that vibrotactilometry is a sensitive test that
      correlates well with the patients' symptoms, while nerve conduction studies are
      less sensitive (49%) in relation to the patients' symptoms. Vibrotactilometry in
      the frequency area of 8-500 Hz is recommended in the screening of ulnar nerve
      entrapment. Nerve conduction studies are recommended in clinically doubtful cases
      to localise the entrapment to the elbow region.

PMID- 10207972
TI  - Reconstruction of eyelid defects: a prefabricated multilayer sandwich graft.
AB  - We have developed a new technique for reconstruction of full thickness eyelid
      defects. A composite three-layer skin-cartilage-mucosal unit is manufactured and
      tailored three-dimensionally. Use of this sandwich graft in our patients proved
      to be simple and safe for eyelid reconstruction and has given good results
      without complications in four patients.

PMID- 10207973
TI  - Infantile fibrosarcoma. Report of two cases.
AB  - We present two cases of infantile fibrosarcoma, one of which was thought to be a
      congenital tumour on the thigh and was initially diagnosed as a haemangioma, and
      the other was a tumour on the trunk. Although both recurred locally after initial
      surgical treatment, wide local re-excision controlled the disease without
      adjuvant treatment.

PMID- 10207974
TI  - Desmoplastic fibroma of the calcaneus treated with a microvascular bone graft.
      Case report.
AB  - A calcaneal desmoplastic fibroma in a 24-year-old woman had previously been
      treated with repeated curettage and bone grafting. Because of a larger recurrence
      a microvascular bone reconstruction was carried out using an osteofascial radial
      forearm flap. She could walk without pain in one year. It has not recurred during
      a five-year follow-up period.

PMID- 10207975
TI  - Immediate autografting of bone in open fractures with bone loss of the hand: a
      preliminary report. Case reports.
AB  - Three patients with open fractures of the hand associated with bone loss were
      treated within four to six hours of injury by corticocancellous bone grafting and
      soft tissue coverage after meticulous debridement, copious irrigation of the
      wounds, and broad-spectrum antibiotics given intravenously. Long term follow-up
      was uneventful and showed that the graft had taken and healed well with early and
      full restoration of function and a good cosmetic result. Immediate
      corticocancellous bone grafting of an injured hand could be used in selected
      cases with well-debrided, surgically clean wounds as long as there is a rich
      blood supply. Adequate bone fixation, soft tissue coverage, and broad-spectrum
      antibiotics given intravenously will remove the risk of infection. Hand
      architecture is corrected while wound contracture and secondary deformity are
      avoided. Both patients' discomfort and hospital costs are considerably reduced.

PMID- 10207976
TI  - Carpal tunnel syndrome after epiphysiolysis of the distal radius in a 5-year-old
      child. Case report.
AB  - Carpal tunnel syndrome after fracture of the distal radius is a well known
      complication in adults, but in small children carpal tunnel syndrome is extremely
      rare. A case of carpal tunnel syndrome in a 5-year-old girl is presented. She had
      a distal epiphysiolysis of the radius, which was treated conservatively. Eight
      weeks after removal of the plaster of Paris she had clinical signs of carpal
      tunnel syndrome after exercise but without new injuries. Conservative treatment
      with a dorsal splint was effective, and all her symptoms disappeared. So
      conservative treatment seems worth considering before operation in similar cases.

PMID- 10207977
TI  - High-resolution ultrasonography in detection and follow-up of a tumour of the
      forearm. Case report.
AB  - A 39-year-old man had a mass in his right flexor medial mid-forearm of unknown
      aetiology for two years. Preoperative high-resolution ultrasonography showed a
      well-defined solid mass with reduced echogenicity. The mass was excised and
      histopathological examination showed neurilemmoma. There had been no recurrence
      of the tumour six months after operation.

PMID- 10207978
TI  - Oncostatin M: development of a pleiotropic cytokine.
AB  - Oncostatin M (OM) is a member of the interleukin-6 (IL-6) cytokine subfamily. The
      binding of OM to its receptor initiates signal transduction through JAK-signal
      transducers and activators of transcription (STAT) pathways and activates
      transcription activators through mitogen-activated protein (MAP) kinases. Results
      of in vitro assays documented that OM modulates cytokine expression and alters
      the production of proteases that down-regulate inflammation. Administration of OM
      to lipopolysaccharide (LPS)-challenged mice lowered serum tumor necrosis factor
      alpha (TNF-alpha) levels and decreased the lethal effects of LPS administration.
      OM also reduced inflammation in animal models of human disease, including
      inflammatory bowel disease, antibody-induced arthritis, and experimental
      autoimmune encephalomyelitis. Preclinical safety studies have been conducted in
      the mouse and monkey. Mice were administered OM (subcutaneously) at 72, 360, or
      1,560 micrograms/kg/day in a 2-wk toxicity study. Decreased body weights occurred
      at 1,560 micrograms/kg. Drug-related changes at 360 and 1,560 micrograms/kg
      consisted of dermal irritation at the injection site, leukopenia, and thymic
      lymphoid depletion; all changes were reversible following a 2-wk recovery period.
      In a 2-wk subcutaneous study in monkeys, OM was administered at 1, 5, 15, 45, or
      150 micrograms/kg/day. At all doses there was reversible, transient inappetence
      and dermal irritation at the injection site. Drug-related changes at 5, 15, 45,
      and 150 micrograms/kg consisted of reversible elevations in both serum amyloid A
      and IL-6, and reversible thymic lymphoid depletion. Transient increases in body
      temperature occurred at 15, 45, and 150 micrograms/kg. The observed spectrum of
      immunomodulatory effects suggests that OM may have therapeutic utility in
      treating chronic inflammatory diseases.

PMID- 10207979
TI  - Coronary arteriopathy in monkeys following administration of CI-1020, an
      endothelin A receptor antagonist.
AB  - A selective non-peptide endothelin A (ETA) receptor antagonist, CI-1020, was
      administered to cynomolgus monkeys intravenously (i.v.) for 2 or 4 wk and orally
      for 4 wk. Groups consisting of 3 animals of each sex received CI-1020 at 1, 5,
      and 10 mg/kg/hr (i.v.) or orally at 250, 500, and 750 mg/kg body weight for 4 wk.
      Control animals received the vehicle only. In a separate experiment, 1 male was
      infused with 10 mg/kg/hr for 2 wk, and Monastral blue dye was administered i.v.
      to facilitate localization of lesions to the vascular walls. One female was
      administered saline and the dye and served as a control. One female at 1 mg/kg/hr
      was found dead at week 2, and 1 female at 5 mg/kg/hr was euthanatized during week
      4 as a result of severe thigh swelling at the catheter site. Macroscopically,
      extramural coronary arteries appeared thickened and nodular in the 4-wk i.v.
      study in the female found dead at 1 mg/kg/hr, in 1 male and 1 female at 5
      mg/kg/hr, and in 2 females at 10 mg/kg/hr. Histologically, Monastral blue pigment
      trapped in the walls of coronary arteries with arteriopathy was observed in the
      male treated with CI-1020 at 10 mg/kg/hr for 2 wk. Extramural coronary
      arteriopathy occurred at all doses in the 4-wk i.v. study, with higher incidence
      occurring in females than in males (7 of 9 treated females compared with 3 of 9
      treated males). In the oral study, 1 female at 500 mg/kg/day and 1 male and 2
      females at 750 mg/kg/day had coronary arteriopathy. Histological changes after 2
      wk of treatment were characterized by intimal thickening, fragmentation of the
      internal elastic lamina, necrosis and edema of the media, and mixed inflammatory
      cell infiltrates in the intima, media, and adventitia. After 4 wk of i.v.
      administration, arteriopathy was characterized by segmental disruption of the
      elastic lamina and intimal and medial fibrosis with complete replacement of
      smooth muscle with fibrous tissue. The adventitia was thickened as a result of
      fibrosis and mixed or mononuclear inflammatory-cell infiltrates. CI-1020
      concentrations were higher in males (1.57 to 29 micrograms/ml) than in females
      (0.974 to 24.4 micrograms/ml) in the i.v. study. Transient systemic exposure with
      high maximum plasma concentration (Cmax) (120-352 micrograms/ml) in the oral
      study was insufficient to provoke arterial changes of the same magnitude as those
      noted with continuous i.v. administration. The regeneration of the media by
      fibrous tissue and the disruption of the elastic lamina may weaken the arterial
      wall and increase the susceptibility of the artery to the development of
      aneurysm.

PMID- 10207980
TI  - Urinary tract toxicity in rats following administration of beta 3-adrenoceptor
      agonists.
AB  - ZD7114, [(S)-4-[2-(2-hydroxy-3 phenoxypropylamine)ethoxy]-N-(2-methoxyethyl)
      phenoxyacetamide], and ZD2079, [(R)-N-(2-[4- (carboxymethyl)phenoxy]ethyl)-N
      (beta-hydroxyphenethyl)ammonium chloride], are beta 3-adrenoceptor stimulants
      with selectivity for brown adipose tissue. ZD7144 is the hydrochloride salt of
      the S-enantiomer of the racemic amide ZD2079. They were developed as potential
      novel treatments for obesity and non-insulin-dependent diabetes mellitus. Male
      and female rats were dosed separately by gavage for a minimum of 28 days with 0,
      10, 50, and 500 mg/kg/day of ZD7114 or with 0, 10, 30, and 150 mg/kg/day of
      ZD2079. Two further groups of male and female rats were dosed with 0 and 500
      mg/kg/day of ZD7114 for 28 days and were then allowed a 6-wk, undosed withdrawal
      period. At high doses, both compounds caused urinary tract toxicity, which
      primarily affected the distal tubules and collecting ducts of the kidney via
      tubular necrosis. They also caused ureteric inflammation, cystitis, and
      accumulation of crystalline inclusions throughout the urinary tract. As a result
      of urinary tract toxicity, affected animals from one or both studies showed
      reduced red blood cell indices, lower platelet counts, and higher white cell
      counts. Blood chemistry revealed lower plasma concentrations of glucose (7.28 +/-
      1.37 compared to 8.11 +/- 0.65 for the control) and total protein (63.42 +/- 3.65
      compared to 69.17 +/- 3.24 for the control) and increased plasma urea (37.15 +/-
      19.96 compared to 8.09 +/- 0.87 for the control). Urinalysis showed an increase
      in the number of crystals, blood, and protein. In the urinary tract, the severe
      crystalluria with accumulation of crystalline material indicated that this may
      have a role in the etiology of the target organ toxicity. Poor solubility of the
      compounds at normal urinary pH was considered a possible mechanism for the
      crystalluria.

PMID- 10207981
TI  - Intestinal T lymphocytes of different rat strains in immunotoxicity.
AB  - In order to study the intestinal mucosal immune cells, with emphasis on single T
      lymphocytes, an inventory was made of single and organized lymphocytes in the
      epithelium and lamina propria of the small intestines of untreated Wistar,
      Fischer 344, and Lewis rats. The single and organized lymphocytes were examined
      microscopically. In addition, the single lymphocytes in the epithelium (IEL) and
      lamina propria (LPL) were analyzed by flow cytometry. Next, the use of flow
      cytometry analysis was explored to detect changes in the IEL T-lymphocyte
      population in subacute oral studies with the immunomodulating agents azathioprine
      and hexachlorobenzene. Untreated random-bred Wistar rats exhibited a large
      interindividual variability in IEL composition, while the variability was small
      in inbred Fischer 344 and Lewis rats. The explorative study with the 2 model
      immunomodulating compounds demonstrated that hexachlorobenzene increased the
      number of intraepithelial T lymphocytes with CD8+ phenotype at the cost of T
      cells with CD4+ phenotype in Lewis rats. Azathioprine did not induce distinct
      effects on the percentages of IEL. The data indicate that the intraepithelial
      lymphocytes in the intestines are a potential target for orally administered
      immunomodulating compounds and should therefore receive more attention in
      toxicologic pathology studies.

PMID- 10207982
TI  - Environmental pathology: new directions and opportunities.
AB  - The National Institute of Environmental Health Sciences (NIEHS) supports a number
      of training programs for predoctoral and postdoctoral (D.V.M., M.D., Ph.D.)
      fellows in toxicology, epidemiology and biostatistics, and environmental
      pathology. At the Experimental Biology meeting in April 1997, the American
      Society of Investigative Pathology (ASIP) sponsored a workshop including
      directors, trainees, and other interested scientists from several environmental
      pathology programs in medical and veterinary colleges. This workshop and a
      related session on "Novel Cell Imaging Techniques for Detection of Cell Injury"
      revealed advances in molecular and cell imaging approaches as reviewed below that
      have a wide applicability to toxicologic pathology.

PMID- 10207983
TI  - The marginalization of hormesis.
AB  - Despite the substantial development and publication of highly reproducible
      toxicological data, the concept of hormetic dose-response relationships was never
      integrated into the mainstream of toxicological thought. Review of the historical
      foundations of the interpretation of the bioassay and assessment of competitive
      theories of dose-response relationships lead to the conclusion that multiple
      factors contributed to the marginalization of hormesis during the middle and
      subsequent decades of the 20th Century. These factors include the following: (a)
      the close association of hormesis with homeopathy, which led to the hostility of
      modern medicine toward homeopathy, thereby creating a guilt-by-association
      framework, and the carryover influence of that hostility toward hormesis in the
      judgements of medically based pharmacologists/toxicologists; (b) the emphasis of
      high-dose effects linked with a lack of appreciation of the significance of the
      implications of low-dose stimulatory effects; (c) the lack of an evolution-based
      mechanism(s) to account for hormetic effects; and (d) lack of appropriate
      scientific advocates to counter aggressive and intellectually powerful critics of
      the hormetic perspective.

PMID- 10207984
TI  - Chemical hormesis: its historical foundations as a biological hypothesis.
AB  - Despite the long history of hormesis-related experimental research, no systematic
      effort to describe its early history has been undertaken. The present paper
      attempts to reconstruct and assess the early history of such research and to
      evaluate how advances in related scientific fields affected the course of
      hormesis-related research. The purpose of this paper is not only to satisfy this
      gap in current knowledge but also to provide a foundation for the assessment of
      how the concept of hormetic dose-response relationships may have affected the
      nature of the bioassay, especially with respect to hazard assessment practices
      within a modern risk assessment framework.

PMID- 10207985
TI  - Effects of carbon dioxide inhalation on hematology, coagulation, and serum
      clinical chemistry values in rats.
AB  - Blood samples from adult male and female Charles River Crl:CD (SD) BR rats were
      collected at weekly intervals for 4 wk to evaluate the effects of inhalation of
      an anesthetic dose of carbon dioxide (CO2) or of a carbon dioxide-oxygen mixture
      (CO2/O2) on hematology, coagulation, and serum biochemistry values. During the
      first 3 wk of the study, rats were assigned to 1 of 3 groups and were bled from
      the orbital sinus once weekly. Prior to the blood collection, rats in group 1
      were exposed to room air only, rats in group 2 received CO2/O2 (approximately
      66%:34% CO2:O2) by inhalation, and rats in group 3 received 100% CO2 by
      inhalation. In the rats exposed to CO2/O2 or CO2, leukocyte counts, lymphocyte
      counts, and glucose values were higher, and aspartate aminotransferase, creatine
      kinase, and calcium values were lower compared with those of rats exposed to room
      air only. Rats exposed to 100% CO2 had slightly (but statistically significant)
      lower mean corpuscular hemoglobin concentration when compared with rats exposed
      only to room air. During week 4, all rats were reassigned to 1 of 2 groups and
      were bled terminally via closed cardiac puncture following exposure to either
      CO2/O2 or CO2. Increased lymphocyte counts (males only) and glucose and chloride
      concentrations were noted for rats exposed to CO2/O2 compared with those exposed
      to CO2. These alterations reiterate the importance of comparing clinical
      pathology values to those of concurrent control groups that have experienced
      blood collection under identical conditions in order to avoid potential errors in
      the interpretation of data.

PMID- 10207986
TI  - Pathological evaluation of the effects of intentional disocclusion and
      overloading occlusion in odontogenesis disorders in N-methylnitrosourea-treated
      hamsters.
AB  - This study compares the effects of disocclusion and overloading occlusion on
      dental lesions. Ten-day-old Syrian hamsters were divided into 4 groups: group I,
      untreated animals; group II, animals whose hemilateral incisors were disoccluded;
      group III, N-methylnitrosourea (MNU)-treated animals; and group IV, MNU-treated
      animals whose hemilateral incisors were disoccluded. The ipsilateral maxillary
      and mandibular incisors were repetitively cut with diamond discs. The hamster is
      easier to anesthetize. Animals received a 0.2% solution of MNU (10 mg/kg body
      weight) intragastrically twice a week for 16 wk. All the cut mandibular incisors
      and the MNU-treated uncut mandibular incisors showed lack of iron deposition on
      the enamel surface. The eruption rate was significantly higher in the cut
      disoccluded incisors of groups II and IV (p < 0.05) and significantly lower in
      the uncut overloaded incisors of groups II and IV (p < 0.05). In the cut
      mandibular incisors of group IV, the degree of the disturbance of odontogenesis
      and the atypical proliferation of odontogenic epithelium were more prominent (p <
      0.02), and the dental lesions occurred earlier. Histologically, the disturbed
      Hertwig's epithelial sheath and the Hertwig's epithelial sheath-like transformed
      U-shaped part and enamel organ seemed to lead to disturbances of amelogenesis and
      detinogenesis as well as to atypical proliferation of odontogenic epithelium
      nests. Thus, this method of disocclusion of the incisors of rodents may represent
      a useful model for the investigation of the effects of various agents on tooth
      formation over a short experimental period.

PMID- 10207987
TI  - Eosinophilic granulated cells comprising a tumor in a Fischer rat.
AB  - A systemic tumor developed in multiple organs, including spleen, bone marrow,
      lymph nodes, liver, ovaries, and thoracic and lumbar vertebrae, of a female
      F344Du/Crj rat. The tumor was composed of round to indented mononuclear cells
      containing abundant large eosinophilic granules in the cytoplasm. The peripheral
      blood smear revealed that the large granules in the cytoplasm of the tumor cells
      were stained basophilic with Giemsa, suggesting a basophil or mast cell origin.
      However, these granules did not show metachromasia with toluidine blue and were
      stained blue to dark blue with phosphotungstic acid hematoxylin. Cellular
      morphology and characteristics in the specific stains of tumor cells suggested
      the development of a tumor of globule leukocytes in a F344Du/Crj rat.

PMID- 10207988
TI  - Marriage of a medium-term liver model to surrogate markers--a practical approach
      for risk and benefit assessment.
AB  - The need for a reliable medium-term alternative to traditional long-term rodent
      test protocols for carcinogen risk assessment is pressing given the immense
      variety of compounds being developed for introduction into the human environment.
      The established lack of a complete correlation between mutagenicity and
      carcinogenicity means that recourse must be made to an in vivo model. Optimally,
      this model should be able to detect not only complete carcinogenic or promoting
      potential but also any ability to inhibit neoplasia. In order to be effective, it
      must take into account the available detailed knowledge on mechanisms of action
      of carcinogens and modulating agents. The Ito model, for which a uniquely
      comprehensive set of background data has already been accumulated, has a solid
      scientific basis; this model utilizes quantitative data for glutathione S
      transferase-positive foci as the preneoplasia-based surrogate end point (PSE). A
      very practical candidate for routine application, its predictive power, its
      flexibility, and its capacity to incorporate a range of mechanism-based surrogate
      end points (MSEs) provide a powerful tool for attainment of the twin goals of
      detecting carcinogenic agents and identifying promising chemopreventors.

PMID- 10207989
TI  - Are we talking to the right people?

PMID- 10207990
TI  - "Have you seen this?" Nonsteroidal anti-inflammatory drug-induced renal papillary
      necrosis in a dog.

PMID- 10207991
TI  - Issues in immunohistochemistry.
AB  - Immunohistochemistry is a powerful technique used to localize specific molecules
      in tissues. Literally thousands of immunoreagents specific for an incredibly
      diverse number of molecules are commercially available, and some of these
      immunoreagents will detect minute quantities of target molecule in tissues.
      However, like any powerful technique, the staining study design must be carefully
      conceived and controlled to avoid misinterpretation.

PMID- 10207992
TI  - Two polypeptide factors that promote differentiation of insect midgut stem cells
      in vitro.
AB  - Isolated stem cells from the midguts of Manduca sexta and Heliothis virescens can
      be induced to differentiate in vitro by either of two polypeptide factors. One of
      the peptides was isolated from culture medium conditioned by differentiating
      mixed midgut cells; we used high performance liquid chromatographic separation
      and Edman degradation of the most prominent active peak. It is a polypeptide with
      30 amino acid residues (3,244 Da), with the sequence
      HVGKTPIVGQPSIPGGPVRLCPGRIRYFKI, and is identical to the C-terminal peptide of
      bovine fetuin. A portion of this molecule (HVGKTPIVGQPSIPGGPVRLCPGRIR) was
      synthesized and was found to be very active in inducing differentiation of H.
      virescens midgut stem cells. It was designated Midgut Differentiation Factor 1
      (MDF1). Proteolysis of bovine fetuin with chymotrypsin allowed isolation of a
      pentamer, Midgut Differentiation Factor 2 (MDF2) with the sequence HRAHY
      corresponding to a portion of the fetuin molecule near MDF1. Synthetic MDF2 was
      also biologically active in midgut stem cell bioassays. Dose response curves
      indicate activity in physiological ranges from 10(-14) to 10(-9) M for MDF1 and
      10(-15) to 10(-5) M for MDF2.

PMID- 10207993
TI  - cDNA of YP4, a follicular epithelium yolk protein subunit, in the moth, Plodia
      interpunctella.
AB  - YP4, a subunit of the follicular epithelium yolk protein in the moth, Plodia
      interpunctella, is produced in the follicle cells during vitellogenesis and after
      secretion is taken up into the oocyte and stored in the yolk spheres for
      utilization during embryogenesis. In order to identify the cDNA clones for YP4, a
      degenerate PCR primer was designed to six amino acid residues identified in the
      NH2-terminal sequence of mature YP4. The YP4 degenerate primer plus T7 reverse
      PCR primer produced a PCR product from a cDNA library for the majority of the YP4
      coding sequence. Combined cDNA and 5' RACE sequencing showed the YP4 transcript
      to be 991 bp in length with a single open reading frame for a predicted
      polypeptide of 299 amino acids. Northern analysis showed a single YP4 transcript
      was present in ovarian RNA that was approximately 1 kb in length. The predicted
      amino acid sequence for YP4 from P. interpunctella was most closely related to
      the predicted YP4 protein from the moth, Galleria mellonella, and the spherulin
      2a protein from the slime mold, Physarum polycephalum.

PMID- 10207994
TI  - Standard free energies of binding of solute to proteins in aqueous medium. Part
      2. Analysis of data obtained from equilibrium dialysis and isopiestic
      experiments.
AB  - In an earlier publication by Chattoraj et al. [Biophysical Chemistry 63 (1996)
      37], a generalized equation for standard free energy of (delta G0) interaction of
      surfactant, inorganic salts and aqueous solvent with protein, forming a single
      phase has been deduced on strict thermodynamic grounds. In the present paper,
      this equation has been utilized to calculate delta G0 in kilojoules per kilogram
      of different proteins for the change of bulk surfactant activity from zero to
      unity in the mole fraction scale. Values of binding interactions of CTAB, MTAB,
      DTAB and SDS to BSA, beta-lactoglobulin, gelatin, casein, myosin, lysozyme and
      their binary and ternary mixtures had already been determined in this laboratory
      at different surfactant concentrations, pH, ionic strength and temperature using
      an equilibrium dialysis technique. Values of delta G0 for saturated protein
      surfactant complexes as well as unsaturated complexes are found to be equal.
      delta G0 is also found to vary linearly with maximum moles of surfactants bound
      to a kilogram of protein or protein mixture and the slope of this linear plot
      represents standard free energy delta G0B for the transfer of 1 mol of surfactant
      from the bulk for binding reaction with protein; -delta G0 values for different
      systems vary widely and the order of their magnitudes represents relative
      affinities of surfactants to proteins. Magnitude of -delta G0B on the other hand
      varies within a narrow range of 32-37 kJ/mol of surfactant. For interaction of
      SDS with BSA, close to the CMC, values of delta G0 are very high due to the
      formation of micelles of protein-bound surfactants. Values of delta G0 for
      negative binding of inorganic salts to proteins and protein mixtures have been
      evaluated using our generalized equation in which excess binding values of water
      and salts have been calculated from the data obtained from our previous
      isopiestic experiments. delta G0 values in these cases are positive due to the
      excess hydration of proteins. Negative values of delta G0 in surfactant
      interaction and positive values of delta G0 for hydration of proteins in the
      presence of neutral salts represent relative affinities of proteins for solute
      and solvent since in all cases, the reference state for delta G0 is the unit mole
      fraction of solute in the aqueous phase.

PMID- 10207995
TI  - The apparently symmetrical hexagonal bilayer hemoglobin from Lumbricus terrestris
      has a large dipole moment.
AB  - The giant approximately 3.6 MDa hexagonal bilayer hemoglobin (HBL Hb) from
      Lumbricus terrestris consists of 12 213-kDa dodecamers of four globin chains ([b
      + a + c]3[d]3) tethered to a central scaffold of approximately 36 non-globin,
      linker subunits L1-L4 (24-32 kDa). Three-dimensional reconstructions obtained by
      electron cryomicroscopy showed it to have a D6 point-group symmetry, with the two
      layers rotated approximately 16 degrees relative to each other. Measurement of
      the dielectric constants of the Hb and the dodecamer over the frequency range 5
      100 kHz indicated relaxation frequencies occurring at 20-40 and 300 kHz,
      respectively, substantially lower than the 700-800 kHz in HbA. The dipole moments
      calculated using Oncley's equation were 17,300 +/- 2300 D and 1400 D for the Hb
      and dodecamer, respectively. The approximately threefold higher dipole moment of
      the dodecamer relative to HbA is consistent with an asymmetric shape in solution
      suggested by small-angle X-ray scattering. Although a two-term Debye equation and
      a prolate ellipsoid of revolution model provided a good fit to the experimental
      dielectric dispersion of the dodecamer, a three-term Debye equation based on an
      oblate ellipsoid of revolution model was required to fit the asymmetric
      dielectric dispersion curve of the Hb: the required additional term may represent
      either an induced dipole moment or a substructure which rotates independently of
      the main permanent dipole component of the Hb. The D6 point-group symmetry
      implies that the dipole moments of the dodecamers cancel out. Thus, in addition
      to a possible contribution from fluctuations of the proton distribution, the
      large dipole moment of the Hb may be due to an asymmetric distribution of the
      heterogeneous linker subunits.

PMID- 10207996
TI  - Importance of long-range interactions in protein folding.
AB  - Long-range interactions play an active role in the stability of protein
      molecules. In this work, we have analyzed the importance of long-range
      interactions in different structural classes of globular proteins in terms of
      residue distances. We found that 85% of residues are involved in long-range
      contacts. The residues occurring in the range of 4-10 residues apart contribute
      more towards long-range contacts in all-alpha proteins while the range is 11-20
      in all-beta proteins. The hydrophobic residues Cys, Ile and Val prefer the 11-20
      range and all other residues prefer the 4-10 range. The residues in all-beta
      proteins have an average of 3-8 long-range contacts whereas the residues in other
      classes have 1-4 long-range contracts. Furthermore, the preference of residue
      pairs to the folding and stability will be discussed.

PMID- 10207998
TI  - A set of conserved PCR primers for the analysis of simple sequence repeat
      polymorphisms in chloroplast genomes of dicotyledonous angiosperms.
AB  - Short runs of mononucleotide repeats are present in chloroplast genomes of higher
      plants. In soybean, rice, and pine, PCR (polymerase chain reaction) with flanking
      primers has shown that the numbers of A or T residues in such repeats are
      variable among closely related taxa. Here we describe a set of primers for
      studying mononucleotide repeat variation in chloroplast DNA of angiosperms where
      database information is limited. A total of 39 (A)n and (T)n repeats (n > or =
      10) were identified in the tobacco chloroplast genome, and DNA sequences
      encompassing these 39 regions were aligned with orthologous DNA sequences in the
      databases. Consensus primer pairs were constructed and used to amplify total
      genomic DNA from a hierarchical set of angiosperms. All 10 primer pairs generated
      PCR products from members of the Solanaceae, and 8 of the 10 were also functional
      in most other angiosperm species. Levels of interspecific polymorphism within the
      genera Nicotiana, Lycopersicon (both Solanaceae), and Actinidia (Actinidiaceae)
      proved to be high, while intraspecific variation in Nicotiana tabacum,
      Lycopersicon esculentum, and Actinidia chinensis was limited. Sequence analysis
      of PCR products from three primer pairs revealed variable numbers of A, G, and T
      residues in mononucleotide arrays as the major cause of polymorphism in
      Actinidia. Our results suggest that universal primers targeted to mononucleotide
      repeats may serve as general tools to study chloroplast variation in angiosperms.

PMID- 10208000
TI  - Disease-resistance related sequences in common bean.
AB  - Primers based on a conserved nucleotide binding site (NBS) found in several
      cloned plant disease resistance genes were used to amplify DNA fragments from the
      genome of common bean (Phaseolus vulgaris). Cloning and sequence analysis of
      these fragments uncovered eight unique classes of disease-resistance related
      sequences. All eight classes contained the conserved kinase 2 motif, and five
      classes contained the kinase 3a motif. Gene expression was noted for five of the
      eight classes of sequences. A clone from the SB3 class mapped 17.8 cM from the Ur
      6 gene that confers resistance to several races of the bean rust pathogen
      Uromyces appendiculatus. Linkage mapping identified microclusters of disease
      resistance related sequence in common bean, and sequences mapped to four linkage
      groups in one population. Comparison with similar sequences from soybean (Glycine
      max) revealed that any one class of common bean disease-resistance related
      sequences was more identical to a soybean NBS-containing sequence than to the
      sequence of another common bean class.

PMID- 10208002
TI  - Molecular characterization of ribosomal gene variation within and among NORs
      segregating in specialized populations of chicken.
AB  - The molecular organization of the 18S, 5.8S, and 28S ribosomal RNA gene repeat
      units, located at the single nucleolus organizer region (NOR) locus in the
      chicken, was investigated in genetically distinct populations of research and
      commercial chickens. Substantial gene repeat variation within and among NORs was
      documented. Intact ribosomal gene repeat size ranged from 11 kb to over 50 kb.
      Unique combinations of ribosomal genes, of different size, were specific to
      particular populations. It was determined that the basis for the ribosomal gene
      repeat size variation was intergenic spacer (IGS) length heterogeneity.
      Interestingly, in different populations, the location of the variation that
      contributes to length heterogeneity was specific to particular IGS subregions. In
      addition to IGS variation, an inbred line of Red Jungle Fowl exhibited coding
      region variation. Ribosomal gene copy number variation was also studied, and line
      averages ranged from 279 to 368. Average rDNA array size (a function of copy
      number and gene repeat length) was calculated for each of the populations and
      found to vary over a range of two megabases, from 5 to 7 Mb.

PMID- 10208003
TI  - Directed termination of the polymerase chain reaction: kinetics and applications
      in mutation detection.
AB  - We describe a PCR-based method (DT-PCR) that integrates both DNA amplification
      and directed chain termination into a single-step process. This method exploits
      unbalanced nucleotide concentrations to induce the polymerase chain reaction to
      terminate at specific nucleotide sites, leading to the generation of two sets of
      nested termination fragments from genomic DNA. The kinetic mechanism underlying
      the termination process is outlined and the application of this method to the
      detection and characterization of mutations in fragments as long as 1 kb is
      described. The method is effective for the analysis of both haploid and diploid
      genomes, and not only allows the recognition of both indels (insertions and
      deletions) and nucleotide substitutions, but also enables the determination of
      their position in a single-step fashion.

PMID- 10208005
TI  - PCR-based analysis of the intergenic spacers of the Nor loci on the A genomes of
      Triticum diploids and polyploids.
AB  - We present DNA sequence data showing population variation in the intergenic
      spacer (IGS) regions of the ribosomal DNAs (rDNAs) on the A genomes of 27 diploid
      and polyploid wheats. PCRs (polymerase chain reactions) specific for the A(m)
      genome gave products with five populations of Triticum monococcum but did not
      give products with AABB or AABBDD wheats. PCRs specific to the A(u) genome of T.
      urartu gave products with all the AABB and AABBDD polyploids that were tested,
      but not with T. monococcum. AAGG tetraploids gave products only with the A(u)
      specific primers, but the AAAAGG hexaploid T. zhukovskyi gave products with both
      the A(u) and A(m) primers. Phylogenetic analysis showed a substantial degree of
      IGS divergence for both the A(m) and A(u) genomes in diploids and polyploids
      compared with other genomes of Triticum and Aegilops. The rate of evolution of
      the IGS is much greater than previously reported for the internal transcribed
      region of the rDNAs but the view that the IGS only gives random noise is
      rejected, the IGS sequences presented here reflecting the general evolutionary
      trends affecting the wheat genome as a whole.

PMID- 10208008
TI  - An example of microsatellite length variation in the mitochondrial genome of
      conifers.
AB  - In the present study, the intergenic region between the mitochondrial genes
      encoding subunit 3 of NADH dehydrogenase (nad3) and ribosomal protein S12 (rps12)
      was shown to contain a Gn mononucleotide microsatellite repeat. This region was
      analysed in 15 species belonging to the genus Pinus and interspecific variation
      was detected in the form of repeat length polymorphism. Sequence analysis of a
      576-bp region containing the microsatellite confirmed that the variability was
      due to expansion and contraction of the repeat motif and that no point mutations
      were present in the coding regions of the two genes. This is the first report of
      the occurrence of a microsatellite polymorphism in plant mitochondria.

PMID- 10208007
TI  - Microsatellite retrieval in lettuce (Lactuca sativa L.).
AB  - By using enriched genomic libraries, microsatellite-containing sequences were
      isolated from lettuce (Lactuca sativa) with high efficiency. With this approach,
      a sizeable fraction (up to 55%) of the clones contained a microsatellite. In
      about half of these clones, primers could be designed for PCR amplification of
      the microsatellite. This yielded 28 primer sets amplifying unambiguously scorable
      products, of which 26 showed polymorphisms in a test set of six lettuce
      varieties. Practically all microsatellite-amplifying primer sets yielded products
      in lettuce's nearest relative, L. serriola, but only half of the primer sets
      yielded products in the more distant species L. saligna and L. virosa. An average
      polymorphism information content (PIC) value of 0.55 and an average number of 3.5
      alleles per locus were in the normal range for a self-fertilizing species like
      lettuce. In addition, the incidental cloning of a microsatellite-containing
      repeat family, apparently specific for Lactuca, is reported and the implications
      for the efficient retrieval of single-locus microsatellite sequences are
      discussed. The microsatellite loci isolated will be useful for distinguishing
      lettuce cultivars and for screening diversity of genetic resources.

PMID- 10208009
TI  - Microfibrils from the arterial subendothelium.
AB  - Microfibrillar structures of the subendothelium are represented by either type VI
      collagen or elastin-associated microfibrils which are also referred to as
      fibrillin-containing microfibrils. These structures are present throughout the
      subendothelium irrespective of the presence of elastin. The localization,
      structure, and protein composition of microfibrils are reviewed. The arterial
      subendothelium is thrombogenic despite its very low content in fibrillar
      collagens. This thrombogenicity is linked to the microfibrillar structures,
      essentially to type VI collagen and to thrombospondin-containing microfibrils.
      Their respective ability to bind the von Willebrand factor and to activate blood
      platelets is discussed.

PMID- 10208010
TI  - Cultivation and transplantation of epidermal keratinocytes.
AB  - Transplantation of autologous cultured keratinocytes is the most advanced area of
      tissue engineering which has clinical application in restoration of skin lesions.
      In vitro, disaggregated keratinocytes undergo activation and after adhesion and
      histogenic aggregation form three-dimensional epithelial sheets suitable for
      grafting on prepared wounds that provide a reparative environment. Epidermal stem
      cells survive and proliferate in culture, retaining their potential to
      differentiate and to produce neoepidermis. Reconstructed skin is physiologically
      compatible to split-thickness autografts. Autotransplantation of cultured
      keratinocytes is a promising technique for gene therapy. In many cases
      allografting of cultured keratinocytes promotes wound healing by stimulation of
      epithelialization. Banking of cryopreserved keratinocytes is a significant
      improvement in usage of cultured keratinocytes for wound healing. Skin
      substitutes reconstructed in vitro that have morphological, biochemical, and
      functional features of the native tissue are of interest as model systems that
      enable extrapolation to situations in vivo.

PMID- 10208011
TI  - Retinoids and mammalian development.
AB  - All vertebrate embryos require retinoic acid (RA) for fulfilment of the
      developmental program encoded in the genome. In mammals, maternal homeostatic
      mechanisms minimize variation of retinoid levels reaching the embryo. Retinol is
      transported as a complex with retinol-binding protein (RBP): transplacental
      transfer of retinol and its uptake by the embryonic tissues involves binding to
      an RBP receptor at the cell surface. Embryonic tissues in which this receptor is
      present also contain the retinol-binding protein CRBP I and the enzymes involved
      in RA synthesis; the same tissues are particularly vulnerable to vitamin A
      deficiency. In the nucleus, the RA signal is transduced by binding to a
      heterodimeric pair of retinoid receptors (RAR/RXR). In general, the receptors
      show functional plasticity, disruption of one RAR or RXR gene having minor or no
      effects on embryogenesis. However, genetic studies indicate that RXR alpha is
      essential for normal development of the heart and eye. Excess RA causes
      abnormalities of many systems; altered susceptibility to RA excess in mice
      lacking RAR gamma or RXR alpha suggests that the teratogenic signal is transduced
      through different receptors compared with physiological RA function in the same
      tissue.

PMID- 10208012
TI  - Gene expression in the epididymis.
AB  - The epididymis is a tubular organ exhibiting vectorial functions of sperm
      concentration, maturation, transport, and storage. The molecular basis for these
      functions is poorly understood. However, it has become increasingly clear that
      regional differences along the length of the duct play a role in epididymal
      physiology and that region-specific gene expression is involved in the formation
      of these differences. Although not an overtly segmented organ, the epididymis
      consists of a series of highly coiled "zones," separated by connective tissue
      septulae and distinct by cell morphology and their pattern of gene expression.
      Thus, it constitutes an interesting mammalian model to study how pattern
      formation is achieved by differential gene activity. A large number of epididymis
      expressed genes have been cloned and analyzed at the molecular level, most of
      them have been characterized by a distinct temporal and spatial expression
      pattern within the organ. Only recently have theories been developed about how
      and when during ontogenesis this pattern formation takes place and what its
      significance might be. This review summarizes the current knowledge on
      regionalized gene expression in the epididymis and presents hypotheses concerning
      its ontogenetic origin and regulation in the adult.

PMID- 10208013
TI  - Roles of reactive oxygen species: signaling and regulation of cellular functions.
AB  - Reactive oxygen species (ROS) are the side products (H2O2, O2.-, and OH.) of
      general metabolism and are also produced specifically by the NADPH oxidase system
      in most cell types. Cells have a very efficient antioxidant defense to counteract
      the toxic effect of ROS. The physiological significance of ROS is that ROS at low
      concentrations are able to mediate cellular functions through the same steps of
      intracellular signaling, which are activated by natural stimuli. Moreover, a
      variety of natural stimuli act through the intracellular formation of ROS that
      change the intracellular redox state (oxidation-reduction). Thus, the redox state
      is a part of intracellular signaling. As such, ROS are now considered signal
      molecules at nontoxic concentrations. Progress has been achieved in studying the
      oxidative activation of gene transcription in animal cells and bacteria. Changes
      in the redox state of intracellular thiols are considered to be an important
      mechanism that regulates cell functions.

PMID- 10208014
TI  - High-density lipoprotein: multipotent effects on cells of the vasculature.
AB  - The epidemiological evidence showing a strong inverse correlation between the
      level of plasma high-density lipoprotein (HDL) and the incidence of heart disease
      suggests that HDL has a protective effect against cardiovascular disease. The
      mechanism of this protective effect has been the raison d'etre for much research.
      The ability of HDL to mediate cholesterol efflux from peripheral tissues has been
      used to explain the cardioprotective effect of HDL. However, there is little
      direct evidence to suggest that in subjects with low plasma levels of HDL the
      rate of cholesterol efflux from peripheral tissues is significantly reduced. This
      observation suggested that HDL may be mediating its protective effect through
      other mechanisms. This review provides an account of the burgeoning evidence that
      HDL has many effects on cellular processes, in addition to the effects on
      cholesterol efflux, and will illustrate the multipotency of this lipoprotein.

PMID- 10208015
TI  - [Gap junctions of the uterine muscle in anomalies of contraction].

PMID- 10208016
TI  - [Preventive medicine in microbial emergencies].

PMID- 10208017
TI  - [Functions and diseases of the frontal lobe].

PMID- 10208018
TI  - [Interaction of neurotransmitters in specific circuits of the brain].

PMID- 10208019
TI  - [Innocuous NSAID: myth or reality?].

PMID- 10208020
TI  - [Ultrasonographic autopsy: a minimally invasive postmortem technique].

PMID- 10208021
TI  - [Oral fluoropyrimidines in oncology].

PMID- 10208022
TI  - [Oxygen production by filament mitochondria. Importance in cancer and
      neurodegeneration].

PMID- 10208023
TI  - [Iodine deficiency and children's rights].

PMID- 10208024
TI  - [Gastroesophageal reflux: an esophageal or gastric disease?].

PMID- 10208025
TI  - [Facial reconstruction on the skull].

PMID- 10208026
TI  - [100th anniversary of the birth of Professor Dr. Dr.h.c. Hugo Grau (15 April 1899
      27 June 1984). Co-founder of the World Association of Veterinary Anatomists and
      the European Association of Veterinary Anatomists].
AB  - On occasion of the centenary of Professor Hugo Grau's birth, in the first part of
      this memorandum his successful life and work, and in the second part his
      forsighted contribution to the foundation of above-mentioned international
      associations of veterinary anatomists will be honoured.

PMID- 10208027
TI  - [Morphogenesis of the submucosal gland of cattle (Bos primigenius f. taurus)].
AB  - In the 10th week of gestation the development of duodenal glands in the bovine
      intestinum starts by circumscript epithelial proliferation. Their secretory
      channels are in contact with the crypts. Already in the early fetal stage
      ultrastructurally there are an inconspicuous equipment with organelles in the
      apical cytoplasm and single globular granules, which demonstrate the
      differentiation of epithelial cells into duodenal glandular cells. Until the mid
      point of the pregnancy the granular endoplasmic reticulum strongly develops as a
      condition for the impressive increase in the formation of the prosecretory
      granules. Finally, in the second half of the pregnancy, granules varying in
      structure and electronic density, but mostly showing an intensively osmiophilic
      and fine granular material, are the predominant cytoplasmic structures. Like in
      goblet cells capsulated vacuoles seem to play a role in the formation of the
      secretory granules. Recent, extensive studies concerning our results have been
      discussed.

PMID- 10208028
TI  - Proportions of various endocrine cells in the pancreatic islets of wood mice
      (Apodemus speciosus).
AB  - Using wood mice (Apodemus speciosus) captured in the wild in Niigata, we analysed
      the proportion of various endocrine cells in pancreatic islets for both
      immunohistochemical and microscopic characteristics. In both the dorsal and
      ventral portions of the pancreas, the centre of the pancreatic islets was
      occupied predominantly by insulin-positive (B) cells, surrounded by glucagon
      positive (A), somatostatin-positive (D), and pancreatic-polypeptide-positive (PP)
      cells. Although the proportions of the various endocrine cells in pancreatic
      islets varied from one mouse to the next, in most animals B cells accounted for
      more than half of all endocrine cells. Dorsal and ventral portions of the
      pancreas differed in the proportions of various endocrine cells, specifically, in
      the A-to-PP cell ratio: the proportion of PP cells higher in the ventral portion.
      The same tendency is seen in humans, rats and mice. Microscopic examinations
      revealed morphologically distinct secretory granules in A, B and D cells. The
      morphology of these granules was similar that of secretory granules found in rats
      and mice.

PMID- 10208029
TI  - Red muscle development of gilthead sea bream Sparus aurata (L.): structural and
      ultrastructural morphometry.
AB  - The transverse red and white muscle area, the superficial red muscle fibres area
      and their percentages of mitochondria (%mit), myofibrils (%myof) and sarcoplasm
      (%sarc) were determined in the Mediterranean teleost gilthead sea bream, Sparus
      aurata (L.). Fish aged from hatching to 78 days were studied. The proportional
      growth of the red and white muscles was higher for the red muscle in the first
      half of the larval stage (1-35 days). Then the opposite relationship was
      observed. The hypertrophic growth of the superficial muscle fibres was continuous
      except in the first week after hatching. The percentage of mitochondria and
      percentage of myofibrils showed a significant change just after the half of the
      larval stage. Whereas the %mit of the superficial muscle fibres was higher than
      %myof from the first week after hatching to 35 days (average 66.64%), then the
      %mit decreased significantly and at 73-78 days both parameters were close to an
      average value of 50%. The meaning of these morphological changes is discussed in
      relation to the functional role of the red muscle of larvae and the onset of the
      gills respiration.

PMID- 10208030
TI  - Ultrastructure of the thyroid gland of the one-humped camel (Camelus
      dromedarius).
AB  - Follicular epithelium of the thyroid gland of the one-humped camel was examined
      by light and electron microscopy. It consisted of a single type of epithelial
      cell which varied from flattened to columnar in shape. Follicular epithelial
      cells were characterized by the presence of markedly dilated cisternae of rough
      surfaced endoplasmic reticulum, well developed Golgi apparatus, abundant small
      vesicles (150 nm to 200 nm in diameter) in the apical cytoplasm, and electron
      dense colloid droplets measuring from 250 nm to 1600 nm. Follicular epithelial
      cells frequently showed apocrine secretion into colloidal lumens. Apocrine
      protrusions with smooth surface were dome-like or balloon-like structures and
      contained a fine granular matrix. These findings indicate that the morphological
      features of the follicular epithelial cells of the thyroid gland of the camel are
      essentially similar to those of mammals except for the presence of apocrine
      secretion, which is unique to the camel.

PMID- 10208031
TI  - [Further contribution on glycogen in fetal intestinal epithelium].
AB  - In the first half of pregnancy the well-known occurrence of glycogen
      incorporation in the supra- and infranuclear cytoplasm of the villous enterocytes
      was verified. This enormous glycan store is evidently of very little functional
      importance. It seems to be an expression of a disordered glycogenolysis. These
      masses of glycogen are incorporated into impressive glycogenosomes, which are the
      predominante cytoplasmic inclusions for a short period of time. According to the
      present results it is not certain whether lysosomal glycogenolysis happens. There
      is no morphological or functional evidence for a utilization og glycogen.

PMID- 10208032
TI  - Morphological and ultrastructural study of carpal organ in adult female wild
      swine.
AB  - The carpal organ of adult female wild swine is a sweat-type gland which secretes
      an odorous substance. The gland consists of 5-7 lobes, each made up of lobules
      with convoluted glandular tubules. The gland secretion is transported in large
      excretory canals which empty from 5 to 7 clearly visible pores. An
      ultrastructural examination showed that the glandular tubules are made up of
      single-layered epithelium with different types of cells. One type, with rather
      electron-dense cytoplasm, is secretory cells full of granular material which
      empties into the tubule lumen. A second cell type has a glycogen-rich,
      transparent cytoplasm. Its role appears to be secreting a watery, electrolyte
      containing liquid. In the intermediate zone of the tubules, there is a third type
      of cell with transparent cytoplasm. Its ultrastructural characteristics seem to
      indicate that its function is to reabsorb the excess watery component. In the
      wall of the glandular tubules, outside the epithelium, there are myoepithelial
      cells which facilitate the movement of the secretions toward the collector canal.

PMID- 10208033
TI  - The nuclei innervating digastric muscle do not project to the hypoglossal nucleus
      in the rat.
AB  - We employed the retrograde neural tracing method using the pseudorabies virus
      bartha strain (PRV-Ba) to investigate the projection from accessory trigeminal
      nucleus (Acc5) or accessary facial nucleus (Acc7) to hypoglossal nucleus (HP).
      After injection of PRV-Ba into the bellies of the digastric muscle, the PRV-Ba
      containing neurones were observed in Acc5 of the cranial belly injected rats and
      Acc7 of caudal belly injected rats ipsilaterally, but not in HP. These results
      suggest that Acc5 and Acc7 may not project to HP and that movements of the
      digastric muscle are not related to cooperation with tongue movements during
      mastication.

PMID- 10208034
TI  - The coexistence of calcitonin gene-related peptide and substance P in
      pericellular arborization and satellite cell of goat trigeminal and nodose
      ganglia.
AB  - Pericellular arborization is reported to be the self-regulating structure in
      sensory ganglia. Although the calcitonin gene-related peptide (CGRP) or substance
      P (SP) immunoreactive pericellular arborization appeared in the sensory ganglia,
      there was no available information that CGRP and SP colocalize in this structure.
      As the attempts to resolve the question described above, the present study was
      undertaken to identify the coexistence of CGRP and SP in pericellular
      arborizations of the goat nodose and trigeminal ganglia by double
      immunohistochemistry. As the results show, CGRP immunoreactivity was present in
      every pericellular arborization containing SP immunoreactivity in trigeminal
      ganglia, however, pericellular network containing CGRP or SP immunoreactivity was
      not present in nodose ganglia. Unexpectedly, a few small satellite elements were
      observed to contain intense CGRP and SP immunoreactivity at the periphery of CGRP
      and SP immunoreactive neurones in nodose ganglia. Therefore, these results
      suggest that CGRP and SP coexist in pericellular arborizations, and that
      satellite cell as well as pericellular arborization may be involved in
      intraganglionic regulation of goat sensory ganglia.

PMID- 10208035
TI  - The distribution of renin in the segments of the renal arterial tree in cats: an
      immunohistochemical and ultrastructural study.
AB  - The intrarenal distribution of renin in the cat kidney was evaluated in a semi
      quantitative immunocytochemical study using a cross-reacting antiserum directed
      against purified renin. In addition, the morphology of the juxtaglomerular
      apparatus was studied electron-microscopically. The majority of renin in the cat
      kidney was located in the distal portion of the afferent arteriole. The values
      for the juxtaglomerular index and the renin-positive portion of the afferent
      arteriole were 30.6 +/- 3.2% and 49.9 +/- 8.3 microns, respectively. In addition,
      scattered renin-positive cells were found far from the vascular pole and even in
      the interlobular artery. Also, some vasa efferentia contained renin-positive
      cells. In 70% of the cats studied, renin-positive cells were located in the
      glomerular mesangium. The majority of the renin-positive mesangial cells were
      located in the vicinity of the glomerular stalk, but in some cases the
      centrilobular mesangium also contained renin-positive cells.

PMID- 10208036
TI  - [Further contribution on the fine structure of fetal goblet cells. Investigations
      on the small intestine of cattle].
AB  - Early in the fetal development, i.e. at the time both of the growth of intestinal
      villi and crypts and the epithelial cell differentiation the goblet cells also
      appear. The maturation of goblet cells progresses during their migration from the
      base of the villi respectively of the crypts to the villous top. As in the bovine
      large intestine there are vesicles and capsulated vacuoles, which contain
      vesicles, as single elements or as conglomerates in the immature goblet cells of
      the small intestine. These images deliver a scenario of the mechanism of
      secretory granule production and probably play a role in the formation of mucus.

PMID- 10208037
TI  - Relationships between kidney mass and body size in some Anseriformes.
AB  - Relationships between kidney mass (KM) and body mass (BM), body length (BL), and
      sternum length (SL) were studied in adults of both sexes of 4 Mergini
      anseriforms: Clangula hyemalis (n = 74), Melanitta fusca (n = 29), M. nigra (n =
      15), and Somateria mollissima (n = 8). The following indices were established for
      the four species and for the Mergini tribe: KM/BM (as per cent body mass), KM/BL,
      and KM/SL. Additionally, allometric equations describing the relationships
      studied were developed for the tribe using mean kidney weights and body
      parameters of males and females of the species examined. The KM/BM indices for
      several anseriform tribes (i.e. Anserini, Anatini, Aythyini and Mergini),
      differing in food and feeding modes, were determined, based on the literature
      data and those obtained in this study. In addition, an allometric equation
      describing the kidney weight-body weight relationship in the Anseriformes order
      was developed as log KM = 0.797 log BM-1.346 (n = 22). The relative kidney size
      in the sea duck species studied showed significant intra- and interspecific
      differences. In addition, clear between-tribes differences in KM/BM were
      revealed. The highest value (1.57%) of the index is typical of the Mergini,
      grouping diving carnivorous sea ducks, while the lowest index (0.65%) is typical
      of the Anserini, a tribe which groups non-diving herbivorous birds.

PMID- 10208038
TI  - [Anatomic and biologic role of the movement of the thorax in dogs and cats].
AB  - Development of the gonometrical measuring method has allowed the respiratory
      movement of the lateral chest wall and the sternum to be investigated. The
      mobility of a single rib varies enormously in gradual transitions. There are
      distinct differences between species. For a number of reasons, the cat can
      achieve more intense thoracic respiration than the dog.

PMID- 10208040
TI  - The need for a home hygiene policy and guidelines on home hygiene.

PMID- 10208039
TI  - [A remembrance of prof. Giuseppe Brotzu: researcher, university teacher,
      politician and public administrator, man. On opening Cephalosporins: the golden
      jubilee].

PMID- 10208041
TI  - [The acceptability of experimentation on the efficacy of an anti-HIV vaccine
      among Italian drug addicts].

PMID- 10208042
TI  - [Enteric viruses and other microorganisms of fecal origin in waters affected by
      sewage effluents].

PMID- 10208043
TI  - [The search for enterovirus in surface waters via RT-PCR: experience on the
      Ticino River].

PMID- 10208044
TI  - QA and health education: two methodologies compared.

PMID- 10208045
TI  - [The primary antitetanus cycle in adults: the contribution of the Fist Aid
      Service to the activities of the territorial health service of the city of
      Pesaro].

PMID- 10208046
TI  - [Bromide residues: an index of environmental contamination in greenhouse
      cultivation].

PMID- 10208047
TI  - Coronary vasoconstriction: where do we stand in 1999. An important, multifaceted
      but elusive role.

PMID- 10208048
TI  - Genetic research stimulates development of individual treatment.

PMID- 10208049
TI  - [Soluble-phase adhesion molecules as biohumoral markers of vascular activation in
      vivo].

PMID- 10208050
TI  - [Hypolipemic therapy in peripheral arterial diseases: reasons of its clinical
      use].

PMID- 10208051
TI  - [Inescapable relativity of normal values in echocardiography].

PMID- 10208052
TI  - [The genetic component of coronary risk. II].

PMID- 10208053
TI  - [Myocardial revascularization with arterial conduits: comparison of bilateral
      internal mammary artery and single internal mammary artery].
AB  - The use of bilateral internal mammary artery (BIMA) grafting for myocardial
      revascularization has been demonstrated to provide long-term benefits compared to
      revascularization using single left internal mammary artery (SIMA) and venous
      conduits. However, it is still controversial whether the use of BIMA is
      associated with a higher hospital mortality and morbidity. The present study
      retrospectively evaluated the possible advantages related to the use of BIMA at 3
      year follow-up and whether the presence of operative risk factors in patients
      with BIMA could limit the application of the procedure in myocardial
      revascularization. We compared two groups of 100 patients matched for
      preoperative clinical characteristics, who underwent myocardial revascularization
      on the left coronary system with BIMA (93 males and 7 females, mean age 59 +/- 4
      years) or with SIMA and venous conduits (86 males and 14 females, mean age 63 +/-
      6 years). Hospital mortality rate was 2% in both groups, the use of BIMA being
      not a significant risk factor for hospital mortality and morbidity. The mean
      follow-up was 36 +/- 6 months for the BIMA group and 40 +/- 10 months for the
      SIMA group. At 3 years, there was no significant differences in the actuarial
      freedom from cardiac death (96 +/- 2% for BIMA vs 94 +/- 2% for SIMA patients),
      myocardial infarction (98 +/- 2 vs 97 +/- 2%), angina (93 +/- 2 vs 91 +/- 2%),
      symptomatic heart failure (92 +/- 3 vs 92 +/- 2%), coronary
      angioplasty/reoperation (96 +/- 2 vs 97 +/- 2% ), and total cardiac events (80 +/
      4 vs 76 +/- 4%). BIMA grafting was not an independent predictor of late cardiac
      events. In 66 patients who underwent a late angiographic or echo-Doppler study,
      the patency rate was 100% for the left mammary artery, 94% for the right mammary
      artery and 69% for venous conduits. In conclusion, myocardial revascularization
      with BIMA in situ is associated with low hospital mortality and morbidity, good
      clinical outcome and excellent patency rate at 3 years, with apparently no
      significant differences when compared to the use of SIMA and venous conduits. The
      low hospital mortality and morbidity and the satisfactory medium-term results in
      our opinion justify a more extensive use of BIMA in myocardial revascularization.

PMID- 10208054
TI  - Histologically proven myocarditis in patients with biventricular dysfunction and
      severe asymptomatic coronary artery disease.
AB  - The aim of our study was to investigate the pathogenesis of the global
      biventricular dysfunction observed in patients with critical coronary artery
      stenosis, but no evidence of myocardial ischemia or infarction. From January 1992
      to January 1997, among consecutive patients undergoing invasive cardiac study
      including biventricular endomyocardial biopsy because of progressive heart
      failure (NYHA functional class III-IV) associated with biventricular dysfunction
      and no history of myocardial ischemic events, 7 patients had severe coronary
      artery disease (three vessel 4 patients; two vessel 1 patient, proximal occlusion
      of left anterior descending artery 2 patients). At two-dimensional
      echocardiography left and right ventricular end-diastolic diameter were 73 +/-
      10.5 and 39 +/- 7 mm, respectively, left ventricular ejection fraction was 0.23
      +/- 6.5 and right ventricular ejection fraction was 0.29 +/- 7.2. Histology
      showed extensive lymphocytic infiltrates with focal myocytolysis meeting the
      Dallas criteria for myocarditis in all patients. Two patients with active
      inflammation received prednisone and azathioprine in addition to conventional
      drug therapy for heart failure. At 6-month follow-up cardiac volume and function
      improved in immunosuppressed patients (left ventricular ejection fraction from 15
      to 50% and from 20 to 38%, respectively) while they remained unchanged in
      conventionally treated patients. In conclusion, global biventricular dysfunction
      in patients with severe asymptomatic coronary artery disease and no evidence of
      previous myocardial infarction may be caused by myocarditis rather than by
      myocardial ischemia or hibernation.

PMID- 10208055
TI  - [Effects of reperfusion and coronary reocclusion on the variability of heart rate
      in patients with acute myocardial infarction].
AB  - The aim of this study was to analyze the very early (first 24 hours) effect of
      successful or failed thrombolytic therapy on the autonomic nervous system. Thirty
      consecutive patients with a first acute myocardial infarction were enrolled in
      the study, and admitted to the Coronary Care Unit within 6 hours of the onset of
      symptoms and treated with systemic thrombolytic therapy. All patients underwent
      24-hour Holter monitoring in order to analyze ST segment variation. The autonomic
      nervous system was evaluated by frequency-domain heart rate variability: low
      frequency/high frequency ratio (LF/HF) was measured at the beginning of Holter
      monitoring (T1), 15 min after reperfusion or 1 hour from the start of
      thrombolytic therapy (T2) and after 24 hours (T3). Reperfusion status was
      assessed by a > or = 50% reduction in ST segment elevation within 90 min of
      thrombolytic therapy, and early CK-MB peak. Early coronary reocclusion was
      detected by early reduction in ST segment elevation followed by stable ST segment
      re-elevation. Twenty patients (66%) showed successful thrombolytic therapy (Group
      1), 5 patients (17%) had no evidence of successful thrombolytic therapy (Group 2)
      and 5 patients (17%) showed an early reocclusion (Group 3). LF/HF ratio values at
      T1 were similar in the three groups (5.66 +/- 1.7 vs 5.65 +/- 1.2 vs 5.51 +/-
      0.9, NS). At T2, LF/HF ratio was significantly higher in Group 1 and 3 than Group
      2 patients (9.21 +/- 1.7 and 11.1 +/- 1.2 vs 5.58 +/- 1.4, respectively, p <
      0.001). In Group 1 LF/HF ratio was significantly lower at T3 when compared with
      T1 and T2 (1.9 +/- 1 vs 5.66 +/- 1.7 and 9.21 +/- 1.7, respectively, p < 0.001).
      Conversely, in Group 3 LF/HF ratio at T3 was similar to values measured at T1
      (5.59 +/- 1.7 vs 5.51 +/- 0.9, respectively, NS) and significantly higher than
      those detected in Group 1. In Group 2, LF/HF ratio resulted substantially
      unchanged at T3 (5.49 +/- 1.7, NS). In conclusion, 1) successful thrombolytic
      therapy induces early beneficial effects on the autonomic nervous system
      function, as shown by increased heart rate variability values, when compared with
      failed thrombolytic therapy; 2) however, during the early period following
      coronary reperfusion, a transient but dramatic increase in sympathetic activity
      is observed. This could trigger coronary flow instability, thus facilitating
      reocclusion, by activating different pathogenetic mechanisms (increased vascular
      tone, platelet activation, thrombogenic factor prevalence); 3) early coronary
      vessel reocclusion precludes favorable effects of reperfusion on sympatho-vagal
      balance observed after the first 24 hours.

PMID- 10208056
TI  - [Oxidative stress and hypercholesterolemia: increase of radical hydroxyl in
      patients with hypercholesterolemia].
AB  - A close relationship exists between high blood cholesterol levels and
      atherosclerosis. This relationship, which represents an important risk factor for
      cardiovascular diseases, may be dependent on enhanced oxidative stress. To
      investigate this hypothesis, we studied 20 patients (12 females and 8 males, aged
      between 40 and 65 years) with high blood cholesterol levels (240-450 mg/dl) but
      without other risk factors for atherosclerosis and 20 healthy individuals matched
      for sex and age, with blood cholesterol levels < 240 mg/dl. We elaborated a
      laboratory technique that identifies two metabolites of the hydroxyl radical, the
      2,3 and the 2,5 dihydroxybenzoic acid (DHBA), in basal conditions and after
      stimulation by 0.5-1 microM formyl-methionine-leucyl-phenylalanine, which is a
      specific activator of leukocytes. Results show that patients with
      hypercholesterolemia have a significant increase of 2,3 e 2,5 DHBA both in basal
      conditions and after stimulation (p = 0.03). A significant correlation (rho =
      0.474; p = 0.004) was found between 2,3-2,5 DHBA and serum cholesterol. This
      study shows that patients with hypercholesterolemia have enhanced leukocyte
      oxidative stress and suggests that cholesterol could play a pivotal role.

PMID- 10208058
TI  - [Case of cardiac amyloidosis associated with IgG-K multiple myeloma in the
      framework of restrictive myocardiopathy].
AB  - Primary amyloidosis, due to amassing of fragments of light chains of IgG, often
      causes cardiac involvement. We describe a 65-year-old woman with multiple myeloma
      efficaciously treated with chemotherapy. Amyloidosis had been supported by myelic
      biopsy. The patient came to our observation because of right heart failure,
      hypotension and syncope: she was treated with a dopamine i.v. and was in
      cachectic status. She had a moderate pericardial effusion. ECG showed reduction
      of QRS amplitude, I degree atrioventricular block, posterior fascicular and right
      bundle branch block. Right cardiac catheterization showed a restrictive
      situation. After 1 week exitus occurred by asystole. In this case, there were
      other involvements by amyloidosis, besides the cardia one: that of autonomic
      nervous system and, probably, surrenal.

PMID- 10208057
TI  - [Left ventricular aneurysm in a patient with mildly dilated cardiomyopathy].
AB  - We describe the case of a patient with mildly dilated idiopathic cardiomyopathy
      and left ventricular aneurysm, diagnosed in absence of a prior clinical history
      and anatomo-pathological features of myocardial infarction. To ascertain the
      diagnosis of idiopathic cardiomyopathy, the patient underwent cardiac
      catheterization with coronary angiography, that showed the lack of epicardial
      artery stenosis and a slow run-off of the contrast. An endomyocardial biopsy
      showed the presence of hypertrophic myocytes and interstitial fibrosis. Moreover,
      a thoracic high resolution computed tomography showed the features of pulmonary
      bilateral basal emphysema, interstitial thickening and bronchiectasis. Alfa1-anti
      trypsin plasma levels were reduced. The patient, because of worsening of clinical
      and hemodynamic conditions, underwent at age of 36 a combined heart-lung
      transplantation. The pathological examination of the native organs confirmed the
      previous diagnosis. At the moment, this is the second report in the literature
      concerning the presence of left ventricular aneurysm in a patient with idiopathic
      cardiomyopathy without an underlying coronary artery disease or prior history of
      myocardial infarction.

PMID- 10208059
TI  - [Verapamil-responsive ventricular tachycardia in small children: a case report
      and review of the literature].
AB  - A case of verapamil-responsive incessant ventricular tachycardia in a 4-year-old
      girl is reported. Oral verapamil alone failed in maintaining stable sinus rhythm.
      With association of oral verapamil and betablockers (nadolol) the patient
      remained asymptomatic without recurrence of ventricular tachycardia over a follow
      up of 1 year. In case of failure of monotherapy with verapamil or betablockers
      alone, an association of both can be effective and safe also in pediatric age.
      Radiofrequency catheter ablation should be reserved, especially in pediatric age,
      only to patients with impaired ventricular function who are not responsive to
      medical therapy.

PMID- 10208061
TI  - Deputizing patients: the feds on the attack.

PMID- 10208060
TI  - Partial anomalous venous return associated with intact atrial septum and
      persistent left superior vena cava: a case report and literature review.
AB  - Left-sided partial anomalous pulmonary venous return (PAPVR) with an intact
      atrial septum is a rare cardiovascular anomaly. This report deals with the case
      of a 22-year-old woman who was referred to our Institution because of resting
      palpitation and exertional dyspnea. Two-dimensional echocardiography revealed
      right heart volume overload and a dilated coronary sinus. A left-sided PAPVR
      draining into a persistent left superior vena cava which, in turn, entered a
      dilated coronary sinus, was correctly detected by magnetic resonance imaging.
      Diagnosis was confirmed by cardiac catheterization. The literature on this
      subject is reviewed.

PMID- 10208062
TI  - Confidentiality of peer review.

PMID- 10208063
TI  - A health information network for Delaware.

PMID- 10208064
TI  - UV radiation and skin cancers.

PMID- 10208065
TI  - Self-reported ethnic status of delivering women, newborn body mass index, blood
      or urine concentrations of toxic metals, and essential elements in sera of
      Norwegian and Russian Arctic populations.
AB  - As part of the Arctic Monitoring and Assessment Programme (AMAP), we assessed
      pregnancy outcome among Sami and Norwegian populations of Finnmark County in
      Norway and Russians living in the Kola Peninsula of Russia using body mass index
      of the newborn child (BMIC) as the main indicator; concentrations of essential
      and toxic elements in biological fluids of delivering women and their children
      served as additional sources of information. At the hospitals of Hammerfest and
      Kirkenes in the period November 1993-June 1994 a total of 107 consecutive women
      gave birth to a child, of whom 15 regarded themselves as Sami. The Russian group
      (N = 151) delivered their children in the same period. The Sami women were
      significantly older than the Russian group (28.5 versus 25.1 years, p = 0.04).
      The mean birth weight was significantly lower in the Sami group compared to non
      Sami Norwegians (p = 0.01), but was of comparable magnitude to that recorded in
      Russia (p = 0.4). For BMIC, the Sami and non-Sami Norwegian results were similar
      (p = 0.2); both were significantly higher than in Russia (p < 0.001). The
      essential elements copper, zinc, selenium and iron (as ferritin) in serum showed
      no differences between the groups, although relatively low levels of serum zinc
      were documented in all populations studied. Blood cadmium concentrations were
      strongly related to smoking frequency. Blood lead and urinary nickel levels were
      significantly higher for the Russian mothers, but did not reach levels of medical
      concern. CONCLUSION: No ethnic differences in concentrations of essential
      elements in biological fluids, nor of cadmium and mercury, were observed.
      However, national differences for lead and nickel were evident. Because of small
      sample size, these conclusions need confirmation. The similar BMIC values
      observed for the non-Sami Norwegian and Sami newborns, compared to the Russian
      group, suggest that BMIC may serve as a good indicator of the nutritional status
      and possibly also the general health condition of neonates.

PMID- 10208067
TI  - Inuit and non-Inuit alcohol consumption in the Baffin Region, NWT, Canada.
AB  - Stereotypes about Inuit drinking would have us believe they are much more likely
      to be users of alcohol compared to other segments of the population. As with many
      other stereotypes, however, this belief is primarily rooted in fiction and
      selective observation. As revealed in a number of self-report surveys regarding
      alcohol use, a smaller proportion of Inuit in the Northwest Territories (NWT)
      have reported drinking when compared to the non-aboriginal of the territory. The
      data presented here serve to further confirm the notion of comparatively less
      prevalent alcohol use among NWT Inuit. Rather than using survey data, however,
      this paper looks to alcohol use indicators derived from territorial liquor
      commission mail order invoices to show that the volume of alcohol consumed by
      Baffin Region Inuit is much less than that of non-Inuit in and outside the
      territory.

PMID- 10208066
TI  - Self-reported seasonal variation in depression at 78 degree north. The Svalbard
      Study.
AB  - STUDY OBJECTIVES: To explore and compare the one year prevalence of self-reported
      depression in two ethnically different populations. DESIGN: A cross-sectional
      study of each population (1988-89 and 1993). SETTING: Norwegians living in
      Longyearbyen, Svalbard, and Russians living in Barentsburg and Pyramiden,
      Svalbard, both representing the world's two northern most regularly inhabited
      settlements. PARTICIPANTS: 506 Norwegians (327 men and 179 women) and 446
      Russians (314 men and 132 women), all 18 years or older, living on Svalbard. MAIN
      RESULTS: Among Russians, the one year prevalence of self-reported depression
      lasting for at least 2 weeks was 26.8% for men and 44.7% for women. Corresponding
      figures for the Norwegians were 10.7 and 15.6%. For the period with polar night
      the figures were 5.5 and 6.7% for Norwegians, and 21.7 and 37.1% for Russian men
      and women, respectively. Depression was most common in the youngest age-group
      among Russians and in the oldest age-group among the Norwegians. CONCLUSION: The
      one year prevalence of depression was 2-3 times higher among Russians compared to
      Norwegians living on Svalbard. For the period with polar night, the figures were
      4-5 times higher for Russians. As both populations are exposed to the same amount
      of daylight, seasonal depression may therefor not solely be a matter of lack of
      daylight. Because the Russian population came from lower latitudes than the
      Norwegians, we hypothesize that insufficient acclimatization after migration to
      the north is essential for the understanding of seasonal variation in depression.

PMID- 10208068
TI  - The nutrient density of present-day and traditional diets and their health
      aspects: the Sami- and lumberjack families living in rural areas of Northern
      Sweden.
AB  - In a rural area of Northern Sweden, the food consumption of 22 Swedish Sami
      families and 32 lumberjack families was recorded. Repeated 24-hour recalls were
      obtained from September 1990 to April 1991. The traditional Sami diet was
      calculated from interviews with old Sami people living today and from information
      from the literature. The nutrient density was well above recommended levels for
      most nutrients except for folate and fiber, in the Sami and lumberjack diets.
      Sami diet was just below NNR for calcium density and the lumberjacks' diet for
      selenium density. The present-day diets of Sami families contain less protein
      than in the past. In lumberjack families today, the intake of energy and fat is
      less than in the past while protein content has been kept constant over time.
      Different aspects of these dietary changes and possible health effects are
      discussed and compared with food consumption in Iceland and Finland in the past.

PMID- 10208069
TI  - The formation of the demarcation line at experimental frostbite.
AB  - Experiments were carried out to gain a better understanding of the pathogenesis
      of frostbite and changes at the demarcation line after freezing and thawing and
      to determine the forming demarcation line as early as possible. These changes
      were investigated by histochemical techniques, by histofluorescence, by
      determining noradrenaline content in the tissue and nerve, by scintigraphy and
      thermography. The experimental animal was New Zealand white rabbit. The frostbite
      was produced using a small laboratory bottle filled with liquid nitrogen pressing
      against the shaved skin in the middle of the proximal part of the ear. Enzyme
      histochemistry was good in demonstrating the demarcation line between
      irreversibly damaged and healing frostbitten tissue. Especially the reaction to
      esterase was the clearest, the demarcation line was visible already after one
      week. The glyoxylic acid-induced fluorescence method was available for showing
      adrenergic nerves around the vessels and the accumulation of catecholamines in
      these nerves in the demarcation line. The result of quantitative measurement of
      catecholamines in the nerve and tissue was similar and the reaction was the most
      powerful during the first three days. Scintigraphy was better than thermography
      and necrotic areas in the middle of the frostbitten area became clearly visible
      after three weeks. It seems that many changes caused by frostbite happen both in
      tissue and cells. The role of catecholamines in vascular circumstances is
      important and that's why chemical or surgical sympathectomy could be useful.

PMID- 10208070
TI  - Trace metals in ancient hair from the Karluk Archaeological Site, Kodiak, Alaska.
AB  - Considerable interest exists in characterizing the extent of changes in
      methylmercury exposures from preindustrial to modern-day times. Hair is often
      preserved over centuries and has been useful in determining the extent of dietary
      trace metal exposures, particularly methylmercury. We examined 16 human hair
      samples taken from human hair bundles buried in the soil of the Karluk One
      Archaeological site located near the current Karluk village on the Kodiak
      Archipelago of Alaska. Hair samples were analyzed for total mercury,
      methylmercury, selenium, and cadmium. The mean total mercury level was 1.33 ppm
      (SD = 1.09). The mean methylmercury level, however, was considerably lower than
      the total mercury concentration: the mean methylmercury level was 0.03 ppm (SD =
      0.02). The mean cadmium level was 0.15 ppm (SD = 0.14) and the mean selenium
      level was 5.22 ppm (SD = 5.73). While the concentration of total mercury in the
      Karluk hair samples is comparable to those observed in ancient hair from other
      locations, direct methylmercury quantization demonstrated that methylmercury
      levels were less than 2% of the total mercury in these hair samples. Because the
      hair was subjected to a variety of environmental influences over the centuries,
      the possibility of degradation of methylmercury in the hair over the last 400 to
      800 years cannot be ruled out. The use of hair from remains found in more
      protected frozen or dry environments may provide the best evidence for the extent
      of preindustrial exposures to methylmercury and other trace metals.

PMID- 10208071
TI  - Coming to grips with a slippery issue: human waste disposal in cold climates.
AB  - Problems associated with sewage treatment and human wastes at high latitudes are
      briefly reviewed. In view of the fact that E. coli and other faecal bacteria can
      survive in the snow and the coastal waters of polar regions, several methods of
      how to deal with sewage outfalls in the Arctic and Antarctic are compared and
      discussed. Some consequences of raw sewage on the health of captive populations
      of a variety of Antarctic invertebrates and fish are described. Locomotion and
      respiration appear to be most affected. However, gaps, both in understanding the
      biological impact of human sewage on polar ecosystems and in finding optimal
      solutions for the disposal and treatment of the wastes generated by people who
      live in polar settlements, unfortunately still remain.

PMID- 10208072
TI  - Brief modification of suggestibility and hypnotic analgesia: too good to be true?
AB  - A 10-minute training procedure, based on the Carleton Skill Training Program, has
      previously been reported to produce substantial increments in responsiveness to
      hypnotic suggestion. The authors attempted to replicate this effect and also
      assessed the impact of the training procedure on hypnotically suggested
      analgesia. Ninety-eight students who had been preselected for high, medium, and
      low levels of initial suggestibility were randomly assigned to experimental and
      control groups. Training failed to increase overall suggestibility scores or to
      enhance the effects of a suggestion for pain reduction. Suggested pain reduction
      was more highly correlated with posttreatment suggestibility scores than with
      pretreatment suggestibility and, in a regression analysis, only posttreatment
      suggestibility predicted pain reduction uniquely.

PMID- 10208074
TI  - Psychophysiological correlates of hypnosis and hypnotic susceptibility.
AB  - This article reviews and summarizes electroencephalographic (EEG)-based research
      on physiological and cognitive indicators of hypnotic responding and hypnotic
      susceptibility, with special attention to the author's programmatic research in
      this area. Evidence that differences in attention levels may account for hypnotic
      depth and individual differences in hypnotizability is provided with traditional
      EEG rhythms, event-related potentials, and 40-Hz EEG activity. The alteration of
      stimulus perception may be a secondary effect with respect to allocation of
      attentional resources. In both nonhypnosis and hypnosis conditions, high
      hypnotizables appeared to show greater task-related EEG hemispheric shifts than
      did low hypnotizables. Findings concerning cognitive and physiological correlates
      of hypnotic analgesia are discussed with respect to hemispheric functioning in
      the apparent control of focused and sustained attention. The conclusion is that
      although a definitive EEG-based signature for hypnosis and hypnotizability is not
      yet established, there are a number of promising leads.

PMID- 10208073
TI  - Clinical hypnosis versus cognitive behavioral training for pain management with
      pediatric cancer patients undergoing bone marrow aspirations.
AB  - A randomized controlled trial was conducted to compare the efficacy of clinical
      hypnosis versus cognitive behavioral (CB) coping skills training in alleviating
      the pain and distress of 30 pediatric cancer patients (age 5 to 15 years)
      undergoing bone marrow aspirations. Patients were randomized to one of three
      groups: hypnosis, a package of CB coping skills, and no intervention. Patients
      who received either hypnosis or CB reported less pain and pain-related anxiety
      than did control patients and less pain and anxiety than at their own baseline.
      Hypnosis and CB were similarly effective in the relief of pain. Results also
      indicated that children reported more anxiety and exhibited more behavioral
      distress in the CB group than in the hypnosis group. It is concluded that
      hypnosis and CB coping skills are effective in preparing pediatric oncology
      patients for bone marrow aspiration.

PMID- 10208076
TI  - The education of school dental therapists.

PMID- 10208075
TI  - Medical hypnosis and orthopedic hand surgery: pain perception, postoperative
      recovery, and therapeutic comfort.
AB  - Orthopedic hand-surgery patients experience severe pain postoperatively, yet they
      must engage in painful exercises and wound care shortly after surgery; poor
      patient involvement may result in loss of function and disfigurement. This study
      tested a hypnosis intervention designed to reduce pain perception, enhance
      postsurgical recovery, and facilitate rehabilitation. Using a quasi-experimental
      research design, 60 hand-surgery patients received either usual treatment or
      usual treatment plus hypnosis. After controlling for gender, race, and
      pretreatment scores, the hypnosis group showed significant decreases in measures
      of perceived pain intensity (PPI), perceived pain affect (PPA), and state
      anxiety. In addition, physician's ratings of progress were significantly higher
      for experimental subjects than for controls, and the experimental group had
      significantly fewer medical complications. These results suggest that a brief
      hypnosis intervention may reduce orthopedic hand-surgery patients' postsurgical
      PPI, PPA, and anxiety; decrease comorbidity; and enhance postsurgical recovery
      and rehabilitation. However, true experimental research designs with other types
      of controls must be employed to determine more fully the contribution of hypnosis
      to improved outcome.

PMID- 10208077
TI  - Prophylactic mineral enrichment of approximal dental plaque.
AB  - Most research on the chemical modification of dental plaque has used material
      from buccal and lingual smooth surfaces of teeth--plaque that is readily
      accessible to treatment solutions. The aim of this study was to test, on the more
      sheltered approximal plaque, the effect of a mouthrinse previously found to be
      effective in raising calcium, phosphate, and fluoride concentrations in
      accessible plaque. Five young adults participated in a blind, cross-over trial to
      compare a Ca-P-MFP-urea test rinse and a NaCl placebo rinse. For 6 days, subjects
      rinsed twice per day after their normal toothbrushing, using 10 ml of rinse
      solution for 30 seconds and a fresh 10 ml for a further 30 seconds. A non
      fluoride toothpaste was used and normal flossing was withheld. Plaque was
      collected before rinsing and again 16 hours after the final rinse from all
      approximal sites except those between the lower anterior teeth. Pre- and post
      rinse calcium values were 291 +/- 100 and 511 +/- 107 nmol/mg protein (mean +/-
      SD) respectively for the test rinse, and 368 +/- 223 and 306 +/- 125 nmol/mg
      protein respectively for the placebo. Analysis of variance showed that the test
      rinse had a significant effect on plaque calcium but not on phosphate or
      fluoride. Mean calcium values of about 2,400 nmol/mg protein have been obtained
      previously in smooth-surface plaque after use of the test rinse. The reduced
      effect here is probably due to restricted access of the rinse solution.

PMID- 10208078
TI  - Guided tissue regeneration in the management of severe periodontal-endodontic
      lesions.
AB  - Diagnosis of combined periodontal-endodontic lesions can prove difficult and
      frustrating. They are often characterised by extensive loss of periodontal
      attachment and alveolar bone, and their successful management depends on careful
      clinical evaluation, accurate diagnosis, and a structured approach to treatment
      planning for both the periodontic and endodontic components. Recent advances in
      regenerative periodontics have led to improved management of periodontal
      endodontic lesions. This paper reviews the management of such lesions in light of
      these recent advances and illustrates this through reports of two patients who
      had severe periodontal involvement.

PMID- 10208079
TI  - Elongated stylohyoid process: a report of three cases.
AB  - The stylohyoid process is part of the stylohyoid chain--the styloid process, the
      stylohyoid ligament, and the lesser cornu of the hyoid bone. The stylohyoid chain
      is derived from the second branchial arch. Mineralisation of the stylohyoid
      ligament and ossification at the tip may increase the length of the styloid
      process. An elongated stylohyoid or styloid process is considered to be the
      source of craniofacial and cervical pain commonly known as Eagle's syndrome. In
      some instances the stylohyoid process may be considerably elongated, yet remain
      asymptomatic. This paper reports three patients with elongated stylohyoid
      processes discovered incidentally on routine radiographic examination.

PMID- 10208080
TI  - Management of children with clefts of the lip or palate: an overview.
AB  - Patients with clefts of the lip and palate present a number of problems
      associated with speech and hearing during early childhood, dental anomalies and
      malocclusion in the developing dentition, and secondary facial deformities and
      emotional "burn out" in adolescence. Appreciation of the differences in
      velopharyngeal function, hearing, speech, growth, and dental development is
      important in understanding the detailed and sequential multidisciplinary
      management required for patients with clefts. The dentist is an important member
      of the cleft-palate team, providing an essential role in establishing a
      preventive plan, monitoring the dental needs of the patient, and motivating and
      educating the patient. A very favourable outcome is now possible for these
      individuals, largely as a result of a team approach to management.

PMID- 10208081
TI  - X-rays and the green factor: balancing efficacy and risk.

PMID- 10208082
TI  - Decline of caries in New Zealand.

PMID- 10208083
TI  - Allergy: etiology and epidemiology.
AB  - The occurrence of atopic disease throughout the world is subject to many
      variables. Differences in methodology and diagnostic criteria for measuring the
      incidence could account for some disparities, but they cannot explain all of
      them. Despite our increasing knowledge of the atopic diseases, improved
      treatments, and early diagnosis, the incidence and prevalence of asthma, allergic
      rhinitis, and atopic dermatitis continue to rise. Ongoing research into the
      etiology and potential risk factors for atopic diseases could lead to the early
      diagnosis, effective treatment, and prevention.

PMID- 10208084
TI  - Pediatric burns.

PMID- 10208085
TI  - Gonorrhea.

PMID- 10208086
TI  - Esophageal foreign bodies.

PMID- 10208087
TI  - Cholesteatomas.

PMID- 10208088
TI  - Index of suspicion. Case 1. Omental torsion.

PMID- 10208089
TI  - Index of suspicion. Case 2. Rocky Mountain spotted fever.

PMID- 10208090
TI  - Index of suspicion. Case 3. Urethral prolapse.

PMID- 10208091
TI  - Spontaneous subarachnoid hemorrhage in children.

PMID- 10208092
TI  - Acute sinusitis.

PMID- 10208093
TI  - [Aging: from marginalization to creativity].

PMID- 10208094
TI  - [Research on the endothelium and new therapeutic strategies in tumors and
      cardiovascular diseases].

PMID- 10208095
TI  - [Prevention of alcohol-related problems. From therapy to primary health care:
      experience at the Udine "Healthy City"].
AB  - This paper is about a community action for the implementation of a WHO
      Collaborative Project on the reduction of hazardous drinking in Primary Health
      Care Settings called "Drink-less". The article stresses the need to shift the
      attention from alcoholic treatment towards the reduction of alcohol consumption.
      After the development of a valid screening instrument and counselling material
      ("Drink-less" Package), the strategies to involve General Practitioners in early
      intervention are studied. A Pilot Project was implemented in the City of Udine by
      the Municipality through its Healthy City Project Office. "Healthy City" is a WHO
      project that stimulates Local Administrations to implement health promotion and
      Community actions through an intersector work. Besides the undoubted validity of
      the overall "Drink-less Project", the study emphasizes the importance of GPs in
      secondary prevention of hazardous drinking and the necessity to re-orient
      programmed action in Public Health and health promotion. "Healthy City WHO
      Project" can be an important tool for the implementation of Community actions in
      Public Health.

PMID- 10208096
TI  - [Primary empty sella syndrome. Observations on 71 cases].
AB  - Primary empty sella syndrome (ESS) is an anatomo-radiological picture
      characterized by the presence of an arachnoid herniation filled with liquor that
      compresses the pituitary against the sellar wall. ESS occurs particularly in
      obese, hypertensive, cephalgic women, it is often asymptomatic but it may be
      associated with ophthalmologic, neurologic and sometime non-characterizing
      endocrine disorders. We report here 71 cases of primary ESS observed and assessed
      during the last fourteen years. The following endocrinological diagnostic
      procedures were carried out: hormonal (RIA) basal profile: FT3, FT4, TSH, PRL,
      ACTH, FSH, LH, 8.00 a.m. and p.m. cortisolemia, Aldo, PRA, DHEA-S, FTe, E2, P,
      PTH, CT, and calcemia and phosphoremia; provocative tests: TRH, GnRH, insulin
      hypoglycemia, etc.; inhibition tests: "overnight" and high dose dexamethasone.
      Clinical, radiological (skull radiographs, CT and/or MRI) and ophthalmologic
      (fundus, visual fields) assessment were made. We found principally cephalgia
      (52/71: 73.2%), hypertension (42/71: 59.1%), obesity (47/71: 66.1%). But we found
      especially mental disorders (57/71: 80.2%), in our knowledge not previously
      reported in the literature, as anxiety or dysthymic disorders with behavioural
      disturbances (chiefly oral compulsion). We found endocrinopathies in 36/71
      (50.7%), isolated or coexisting in some patients: hyperPRL (14%), hypopituitarism
      (10.4%), hypogonadism (7%), diabetes insipidus (2.8%), hyperACTH (1.4%), hypoGH
      (15.4%), pituitary adenomas (8.4%). Several hypothalamic illness show a clinical
      picture including mental disorders and obesity. The Authors hypothesize that the
      ESS may be a "new" hypothalamic syndrome (compression/stretching on hypophysis
      and/or hypophyseal stalk by arachnoidocele; disorder of some hormones and
      neurotransmitters as leptin, neuropeptide Y, orexins, POMC-derived peptides,
      etc).

PMID- 10208097
TI  - [Association of Lynch syndrome and non-Hodgkin's malignant lymphoma. A case
      report].
AB  - A patient is described, with Lynch syndrome, typified by hereditary appearance in
      young age of synchronous and metachronous proximal colorectal cancer, without
      polyposis, and often associated with extracolonic cancer, particularly ovarian
      and endometrial carcinomas. The study of our patient's pedigree showed the
      occurrence of eleven colonic cancers. Our patient had ovarian carcinoma, tumor of
      the rectum and non-Hodgkin's lymphoma.

PMID- 10208098
TI  - [Therapy with melatonin does not suppress its endogenous production in healthy
      volunteers].

PMID- 10208100
TI  - [Dynamics of ascitic fluid in decompensated cirrhosis].
AB  - The ascitic fluid in decompensated liver cirrhosis constitutes a continuously
      circulating pool which carries on sustained water exchanges with plasma and
      extracellular fluids through the whole peritoneal membrane. The actual ascites
      volume results therefore from the steady-state between the formation and
      reabsorption transperitoneal water flows. The ascitic reabsorption concerns both
      the "iso-osmotic" (i.e. the portion bound to the ascitic proteins and solutes)
      and the "free-water" (i.e. the amount exceeding the osmotic bounding ability of
      the peritoneal solutes) fractions of total ascitic water. By means of a simple
      dilution test, it is possible an in vivo estimation of both the ascites volume
      and the rate of transperitoneal free-water reabsorption, which is the actual free
      water peritoneal clearance (CPAL) and an evaluation of the total intra-abdominal
      pressure (PIA). PIA results from the sum of the ascitic hydrostatic pressure, and
      the tension of the abdominal wall. Diuretic administration is able to
      significantly reduce CPAL, inducing a negative sodium balance and thus leading to
      a readjustment of ascites steady-state. This fact may cause reductions of ascites
      volume and PIA only after several days of diuretic treatment. An acute diuretic
      treatment by itself, even if intensive and resulting in a rapid diuresis and a
      significant modification of CPAL, does not appear able to determine rapid and
      detectable modifications of PIA. CPAL has an intrinsic prognostic value in
      patients with decompensated cirrhosis, since the cumulative mortality was
      reported to be significantly higher in the patients with lower CPAL levels. The
      peritoneal clearance ability may be regarded as a compensatory mechanisms of
      portal hypertension, and its estimate may be a reliable index of patient's
      aptitude to a lower hydro-retentive trend, which is in turn correlated to a
      greater cirrhosis severity and a worse prognosis.

PMID- 10208099
TI  - [New antithrombotic drugs].

PMID- 10208101
TI  - [Hypo-osmolar hyponatremic syndromes: physiopathology and clinical aspects].
AB  - Hyponatremia in virtually all patients results from water retention due to an
      inability to excrete ingested water. In most cases, this defect represents the
      persistent secretion of ADH (such as in effective circulating volume depletion,
      and in the syndrome of inappropriate ADH secretion), although free water
      excretion can also be limited in disorders in which ADH levels may be
      appropriately suppressed (such as in advanced renal failure, and in primary
      polydipsia). The symptoms of hyponatremia primarily reflect neurologic
      dysfunction induced by cerebral edema and are related both to the severity and to
      the rapidity of reductions in the plasma sodium concentration. The degree of
      cerebral edema which occurs in acute hyponatremia is much less with chronic
      hyponatremia, because the brain cells lose solutes, leading to the osmotic
      movement of water out the cells and less brain swelling. In general, hyponatremia
      is corrected acutely by giving Na+ to patients who are volume-depleted and by
      restricting water intake in patients who are normovolemic or edematous. The
      optimal rate of correction should be defined to prevent the risk of central
      demyelinating lesions.

PMID- 10208102
TI  - [NSAID-induced gastrointestinal diseases: recent data on pathogenesis and
      prevention].
AB  - Our knowledge of the mechanism by which aspirin and traditional NSAIDs work and
      damage the gastrointestinal mucosa, recently markedly improved, has suggested a
      number of measures for the prevention of the NSAID-induced GI lesions. Among
      these, perhaps the most innovative approach seems to be the nitric oxide
      releasing NSAIDs or compounds, like amtolmetin guacyl, that work by increasing
      the endogenous biosynthesis of NO selectively at gastric mucosa level. Further
      data, stemming from large RCTs and confirming the results of experimental studies
      and the initial clinical experiences, are needed to better define the true
      clinical impact of this approach.

PMID- 10208103
TI  - Proton magnetic resonance spectroscopy (1H MRS) in patients with sporadic
      cerebellar degeneration.
AB  - The authors studied 23 patients with cerebellar degeneration including multiple
      systemic atrophy (MSA) and cerebellar cortical atrophy (CCA) by proton magnetic
      resonance spectroscopy (1H-MRS). 1H-MRS allowed noninvasive measurement of the
      signal intensities derived from N-acetylaspartate (NAA), creatine +
      phosphocreatine (CRE), and choline-containing compounds (CHO). There was
      significant reduction of the NAA/CRE level in the frontal cortex, putamen,
      cerebellar hemisphere and cerebellar vermis of patients with MSA, and in the
      frontal cortex, cerebellar hemisphere and cerebellar vermis of patients with CCA
      as compared with those of normal controls. There was significant reduction of the
      NAA/CRE level also in the putamen of patients with MSA as compared with that of
      patients with CCA. These results indicated the presence of a degenerative process
      and/or functional impairment in the frontal cortex and putamen of patients with
      MSA and in the frontal cortex of patients with CCA, in addition to a degenerative
      process in the cerebellum. There was a significant correlation between the
      NAA/CRE level and the severity of clinical signs. 1H-MRS is valuable in providing
      information regarding the pathophysiology and the progress of cerebellar
      degenerative diseases.

PMID- 10208104
TI  - Cranial magnetic resonance imaging findings in bacterial endocarditis: the
      neuroimaging spectrum of septic brain embolization demonstrated in twelve
      patients.
AB  - Infective endocarditis (IE) is an elusive systemic disorder that is often
      associated with neurologic complications. The contribution of brain magnetic
      resonance imaging (MRI) to the diagnosis of IE and the spectrum of such findings
      has been only sparsely described previously. The authors report cranial MRI
      findings in 12 patients with IE. Each of the patients had MRI evidence of
      cerebral embolization, with multiple brain lesions noted in most patients (n =
      10). Cortical branch infarction was the most common lesion (n = 8), which usually
      involved the distal middle cerebral artery tree. The next most common finding (n
      = 7) was numerous small embolic lesions which typically lodged in the
      supratentorial gray-white junction, some of which were clinically silent and many
      of which enhanced (probable microabscesses). Brain hemorrhages were noted in four
      patients, most commonly subarachnoid hemorrhage (n = 3). Two patients developed
      multiple frank parenchymal macroabscesses/cerebritis lesions. A previously
      unreported finding in septic embolization, a stroke that became infected with
      abscess formation ("septic infarction"), was noted in two patients. MRI showed
      orbital cellulitis in two patients. Most patients studied with gadolinium showed
      enhancement of lesions (n = 5/8). The authors conclude that cranial MRI may be a
      valuable tool in the evaluation of patients with IE. The presence of
      characteristic cranial MRI lesions, especially of multiple types, may prompt
      early diagnosis and treatment.

PMID- 10208105
TI  - Feature extraction for MRI segmentation.
AB  - Magnetic resonance images (MRIs) of the brain are segmented to measure the
      efficacy of treatment strategies for brain tumors. To date, no reproducible
      technique for measuring tumor size is available to the clinician, which hampers
      progress of the search for good treatment protocols. Many segmentation techniques
      have been proposed, but the representation (features) of the MRI data has
      received little attention. A genetic algorithm (GA) search was used to discover a
      feature set from multi-spectral MRI data. Segmentations were performed using the
      fuzzy c-means (FCM) clustering technique. Seventeen MRI data sets from five
      patients were evaluated. The GA feature set produces a more accurate
      segmentation. The GA fitness function that achieves the best results is the
      Wilks's lambda statistic when applied to FCM clusters. Compared to linear
      discriminant analysis, which requires class labels, the same or better accuracy
      is obtained by the features constructed from a GA search without class labels,
      allowing fully operator independent segmentation. The GA approach therefore
      provides a better starting point for the measurement of the response of a brain
      tumor to treatment.

PMID- 10208106
TI  - Lesion localization in acute stroke patients with risk of aspiration.
AB  - The objective of this prospective study was to determine whether specific
      neuroanatomical sites were associated with increased risk of aspiration in acute
      stroke patients. Videofluoroscopic swallow studies (VSS) and computed tomography
      or magnetic resonance imaging scans were completed on consecutive male stroke
      patients (n = 54). Videofluoroscopic swallow studies were scored on a scale from
      0 (normal swallowing) to 4 (severe dysphagia). Patients with scores of 0-1 were
      grouped together as having no risk of aspiration, and patients with scores of 2-4
      were grouped together as having a risk of aspiration. Lesion analyses revealed
      that location appeared to be more critical than hemisphere or lesion size in
      predicting patients at risk of aspiration. Anterior locations and subcortical
      periventricular white matter sites were commonly lesioned in patients with risk
      of aspiration, whereas patients without risk of aspiration were more likely to
      have posterior lesions and lesions to subcortical gray matter structures. These
      data demonstrate that swallowing appears to be mediated by a distributed neural
      network that involves both cerebral hemispheres with descending input to the
      medulla; however, specific lesion locations may put patients at a greater risk of
      aspiration.

PMID- 10208107
TI  - Diagnosis of MCA-occlusion and monitoring of systemic thrombolytic therapy with
      contrast enhanced transcranial duplex-sonography.
AB  - A case of a successful systemic thrombolysis of an acute middle carotid artery
      occlusion is reported. The case underlines the role of contrast-enhanced
      transcranial color-coded duplex sonography as a noninvasive technique for rapid
      diagnosis of vessel occlusion in acute stroke. The diagnostic potential of
      transcranial color-coded duplex sonography for indication and monitoring of
      intravenous systemic thrombolytic therapy is demonstrated.

PMID- 10208108
TI  - Diagnostic benefit of echocontrast enhancement for the insufficient transtemporal
      bone window.
AB  - Echocontrast agents (ECA) are known to improve transcranial color-coded duplex
      (TCCD) imaging, but its diagnostic benefit in the routine clinical setting has
      not clearly been defined. The authors investigated the diagnostic benefit of ECA
      application in 54 patients with insufficient transtemporal bone window,
      consecutively referred to their ultrasound laboratory. According to the
      precontrast imaging quality, patients were assigned to three categories: A, no
      intracranial structures or vessel segments visible on B-mode imaging and TCCD (n
      = 5); and intracranial structures visible on B-mode imaging and vessel segments
      less than 5 mm in length (B, n = 21), or larger than 5 mm in length (C, n = 28)
      visible on TCCD. The effect of the echocontrast enhancement was assessed with
      respect to signal enhancement, imaging quality, and diagnostic confidence. In 49
      out of 54 patients (91%), a significant improvement of the imaging quality was
      noted, enabling 43 (80%) neurovascular diagnoses of sufficient diagnostic
      confidence. The diagnostic ECA effect was strongly dependent on the precontrast
      imaging quality: upon echoenhancement, a satisfactory image quality was obtained
      in none of the patients of category A, as opposed to 16 (76%) and 27 (96%)
      patients of categories B and C, respectively. In summary, in 80% of our
      consecutive patient series with insufficient transtemporal bone window,
      application of ECA allowed for a conclusive TCCD study. Properties of the
      transtemporal precontrast scans are strongly predictive of the diagnostic benefit
      and should be taken into the decisive consideration.

PMID- 10208109
TI  - Multimodality monitoring during passive tilt and Valsalva maneuver under
      hypercapnia.
AB  - In occlusive cerebrovascular disease cerebral blood flow (CBF) autoregulation can
      be impaired and constant CBF during fluctuations in blood pressure (BP) cannot be
      guaranteed. Therefore, an assessment of cerebral autoregulation should consider
      not only responsiveness to CO2 or Diamox. Passive tilting (PT) and Valsalva
      maneuver (VM) are established tests for cardiovascular autoregulatory function by
      provoking BP changes. To develop a comprehensive test for vasomotor reactivity
      with a potential increase of sensitivity and specificity, the authors combined
      these maneuvers. Blood pressure, corrected to represent arterial pressure at the
      level of the circle of Willis, middle cerebral artery Doppler frequencies (DF),
      heart rate (HR) and endtidal partial pressure of CO2 (PtCO2) were measured
      continuously and noninvasively in 81 healthy subjects (19-74 years). Passive tilt
      and Valsalva maneuver were performed under normocapnia (mean, 39 + 4 mmHg CO2)
      and under hypercapnia (mean, 51 + 5 mm Hg CO2). Resting BP, HR, and DF increased
      significantly under hypercapnia. Under normocapnia and hypercapnia, PT induced
      only minor, nonsignificant changes in mean BP at the level of the circle of
      Willis compared to baseline (normocapnia: + 2 + 15 mm Hg; hypercapnia: -3 +/- 13
      mm Hg). This corresponded with a nonsignificant decrease of the mean of DF
      (normocapnia: -4 +/- 11%; hypercapnia -6 +/- 12%). Orthostasis reduced
      pulsatility of BP by a predominantly diastolic increase of BP without significant
      changes in pulsatility of DF. Valsalva maneuver, with its characteristic rapid
      changes of BP due to elevated intrathoracic pressure, showed no significant BP
      differences in changes to baseline between normocapnic and hypercapnic
      conditions. Under both conditions the decrease in BP in phase II was accompanied
      by significantly increased pulsatility index ratio (PIDF/PIBP). Valsalva maneuver
      and PT as established tests in autonomic control of circulation provoked not only
      changes in time-mean of BP but also in pulsatility of BP. The significant
      increase in pulsatility ratio and decrease of the DF/BP ratio during normocapnia
      and hypercapnia indicated preserved CBF autoregulation within a wide range of CO2
      partial pressures. Hypercapnia did not significantly influence the autoregulatory
      indices during VM and PT. Physiologically submaximally dilated cerebral
      arterioles can guarantee unchanged dynamics of cerebral autoregulation. Combined
      BP and MCA-DF assessment under hypercapnia enables investigating the effect of
      rapid changes of blood pressure on CO2-induced predilated cerebral arterioles.
      Assuming no interference of hypercapnia-induced vasodilation, VM, with its rapid,
      distinct changes in BP, seems especially to be adequate provocation for CBF
      autoregulation. This combined vasomotor reactivity might provide a more sensitive
      diagnostic tool to detect impaired cerebral autoregulation very early.

PMID- 10208110
TI  - Orthostasis as a test for cerebral autoregulation in normal persons and patients
      with carotid artery disease.
AB  - Orthostasis reduces mean flow velocity (FVmean) in cerebral arteries. This might
      be used as an alternative provocation test for cerebral hemodynamics in patients
      with carotid artery disease (CAD). In 21 unilateral CAD patients and 21 controls,
      FVmean in both middle cerebral arteries (MCA) was measured by transcranial
      Doppler, together with blood pressure (BP) and heart rate (HR) during a tilt
      table test. Cerebrovascular reserve (CVR) was measured by an acetazolamide test.
      In all cases, FVmean dropped to a lower level (controls: 81.9 +/- 9.4% of
      baseline; patients: 84.3 +/- 7.9% symptomatic side, 85.6 +/- 9.0% contralateral).
      Impaired CVR patients showed a smaller (p < 0.01) decrease (90.6 +/- 3.3%)
      compared to contralateral (84.9 +/- 6.0%), to normal CVR patients (81.1 +/- 7.8%)
      and to controls. Heart rate increased in both groups (controls: +16.6 +/- 9.9%,
      patients +10.3 +/- 9.9%; p < 0.01); BP showed no change. Orthostasis induces a
      decrease of MCA FVmean as already previously described. This decrease is
      significantly smaller in patients with impaired CVR. Since BP does not change,
      some authors explain the lower MCA Fvmean during orthostasis as caused by
      sympathetic induced vasoconstriction of cerebral resistance vessels. The authors
      speculate that in impaired CVR-patients autoregulative protection against
      ischemia might limit vasoconstriction. In combination with standard tests for
      measurement of CVR, this test might be useful for evaluation of cerebral
      autoregulation.

PMID- 10208111
TI  - Pontine cryptococcoma in a nonimmunocompromised individual: MRI characteristics.
AB  - The case of a pontine cryptococcoma in a nonimmunocompromised, previously healthy
      16-year-old boy is presented. The patient had slowly progressive brainstem signs
      with right cranial nerves V, VII, and VIII palsies, and contralateral
      corticospinal and spinothalamic deficits. Magnetic resonance images (MRI)
      revealed, within the right pons, a 1-cm diameter round mass lesion, hypointense
      on T1-weighted images, hyperintense on T2-weighted images, and with rim
      enhancement after infusion of gadopentetate dimeglumine. This is the only report
      of the MRI findings in an isolated pontine cryptococcoma in an immunocompetent
      patient. Early recognition of this specific MRI pattern is essential, because
      complete recovery can be achieved with prompt antifungal treatment.

PMID- 10208112
TI  - Diaschisis in chronic viral encephalitis with Koshevnikov syndrome.
AB  - The authors report a 61-year-old man with chronic viral encephalitis and
      Koshevnikov syndrome occurring 42 months after initial symptom of right
      hemiparesis. Serial computed tomography of the brain showed changes in the
      attenuation of the left temporal lobe lesion over time. Magnetic resonance images
      of the brain showed enlargement of left temporoparietooccipital lobes with
      cortical gyral enhancement on T1-weighted images following intravenous
      administration of gadolinium-DTPA. 99mTc-HMPAO single-photon emission
      computerized tomography showed increased radioactivity and hyperperfusion in the
      left temporoparietal region with paradoxically decreased local tissue perfusion
      at the contralateral right hemisphere. Follow-up magnetic resonance images of the
      brain 4 years later showed atrophy of bilateral cerebral hemispheres. We
      postulate that a "transcallosal diaschisis" with subsequent degeneration is a
      possible mechanism. A brain biopsy from the left temporal lobe lesion showed
      pictures compatible with viral encephalitis probably herpes simplex encephalitis.

PMID- 10208113
TI  - Doppler pulse waveform analysis of carotid and middle cerebral artery flow in a
      patient with an intra-aortic balloon pump.
AB  - A 60-year-old man with intractable congestive heart failure (CHF) had an intra
      aortic balloon pump placed to augment coronary artery perfusion. During the
      evaluation prior to heart transplant, carotid and transcranial Doppler
      ultrasonography (TCD) was performed. The authors report the findings of Doppler
      waveform analysis and the presence of balloon pump artifact which caused
      difficulty in distinguishing between internal and external carotid arteries.
      Higher blood flow velocity during diastole and diastolic runoff
      characteristically seen while insonating the internal carotid artery enabled that
      distinction.

PMID- 10208114
TI  - An easy method to accelerate ictal SPECT.

PMID- 10208115
TI  - Complementary medicine. Fact and fiction about chiropractic.

PMID- 10208116
TI  - I am undergoing treatment for hypertension and have been taking 200 mg of vitamin
      E daily for the past few years. I read that even lower doses might raise my risk
      of having a hemorrhagic stroke. Is this true?

PMID- 10208117
TI  - Coronary disease. Treat heart failure early and often.

PMID- 10208118
TI  - Mild thyroid disease. To treat or not to treat.

PMID- 10208119
TI  - A second look at white-coat hypertension.

PMID- 10208120
TI  - Herbs for bowel problems?

PMID- 10208121
TI  - Update: influenza activity--United States, 1998-99 season.
AB  - This report summarizes influenza activity in the United States from October 4,
      1998, through February 27, 1999. It also presents results of an investigation of
      an influenza outbreak among staff and residents at one long-term-care facility
      (LTCF), and estimates the 1998-99 influenza vaccine effectiveness against the
      circulating influenza A(H3N2) viruses at that facility. Based on influenza
      surveillance data, influenza activity in the United States began to increase in
      mid-January 1999 and remained elevated in most regions of the country through the
      week ending February 27.

PMID- 10208122
TI  - Decrease in infant mortality and sudden infant death syndrome among Northwest
      American Indians and Alaskan Natives--Pacific Northwest, 1985-1996.
AB  - Although the infant mortality rate (IMR) has steadily declined in the United
      States since the early 1900s, the rate varies among racial/ethnic populations. A
      goal of the national health objectives for 2010 is to eliminate racial/ethnic
      health disparities (U.S. Department of Health and Human Services, unpublished
      data, 1999). Historically, IMRs among American Indians and Alaskan Natives
      (AI/AN) have been high. In addition, IMRs have varied among AI/AN populations. To
      determine recent trends in infant mortality among Northwest AI/AN, the Northwest
      Portland Area Indian Health Board (NPAIHB) analyzed annual IMRs among AI/AN in
      Idaho, Oregon, and Washington. In addition, because sudden infant death syndrome
      (SIDS) is the major contributor to excess infant mortality in Northwest AI/AN,
      NPAIHB analyzed SIDS rates to determine whether the decline in SIDS rates in the
      United States also was occurring among Northwest AI/AN. This report summarizes
      the results of this analysis and documents dramatic decreases in both SIDS and
      non-SIDS infant mortality.

PMID- 10208123
TI  - Preterm singleton births--United States, 1989-1996.
AB  - Preterm birth (birth at <37 completed weeks of gestation) is the second leading
      cause of neonatal mortality in the United States. Preterm birthrates differ by
      race; in 1996, black infants were 1.8 times more likely than white infants to be
      preterm. From 1989 through 1996, the overall rate of preterm birth (per 1000 live
      born infants) increased 4%, and the rate of multiple births (e.g., twins,
      triplets, or other higher-order births) increased 19%. Multiple births are
      associated with preterm birth; trends in preterm births independent of the
      influence of multiple births have not been fully explored. To characterize race-
      and ethnicity-specific trends in preterm birth independent of multiple births,
      data from U.S. birth certificates for 1989-1996 were analyzed for singleton
      births only. This report summarizes the results of this analysis and indicates
      that although singleton preterm birthrates are stable overall, substantial
      changes in rates occurred in some racial/ethnic subgroups.

PMID- 10208124
TI  - Incidence of foodborne illnesses: preliminary data from the Foodborne Diseases
      Active Surveillance Network (FoodNet)--United States, 1998.
AB  - Estimates of the magnitude of foodborne illness in the United States have been
      imprecise. To quantify, better understand, and more precisely monitor foodborne
      illness, since 1996 the Foodborne Diseases Active Surveillance Network (FoodNet)
      has collected data to monitor nine foodborne diseases in selected U.S. sites.
      This report describes preliminary data from FoodNet surveillance for 1998 and
      compares findings with those for 1996 and 1997; compared with 1996, the overall
      incidence of the foodborne illnesses under surveillance during 1998 declined,
      particularly for salmonellosis and campylobacteriosis, and the data continued to
      demonstrate regional and seasonal differences in the reported incidence of
      diseases.

PMID- 10208125
TI  - Advances in the use of computed tomography.

PMID- 10208126
TI  - Risk of stroke in users of oral contraceptives.

PMID- 10208127
TI  - Putting a new face on women's health.

PMID- 10208128
TI  - High-tech angina relief explored in treatment trials.

PMID- 10208129
TI  - Breathing life into an NIH exhibit on asthma.

PMID- 10208130
TI  - From the Centers for Disease Control and Prevention. Outbreaks of
      gastrointestinal illness of unknown etiology associated with eating burritos-
      United States, October 1997-October 1998.

PMID- 10208131
TI  - From the Centers for Disease Control and Prevention. Total tooth loss among
      persons aged > or =65 years--selected states, 1995-1997.

PMID- 10208132
TI  - From the Centers for Disease Control and Prevention. Norwalk-like viral
      gastroenteritis in US Army trainees--Texas, 1998.

PMID- 10208133
TI  - Computer-based support systems for women with breast cancer.

PMID- 10208134
TI  - Postexposure prophylaxis following HIV exposure.

PMID- 10208135
TI  - Postexposure prophylaxis following HIV exposure.

PMID- 10208136
TI  - Acupuncture and amitriptyline for HIV-related peripheral neuropathic pain.

PMID- 10208137
TI  - Acupuncture and amitriptyline for HIV-related peripheral neuropathic pain.

PMID- 10208138
TI  - Acupuncture and amitriptyline for HIV-related peripheral neuropathic pain.

PMID- 10208139
TI  - Electronic information retrieval by physicians and medical librarians.

PMID- 10208140
TI  - Medicaid and children's access to care.

PMID- 10208141
TI  - Low-fat dairy foods and colonic epithelial cell proliferation.

PMID- 10208142
TI  - Anabolic effects of nandrolone decanoate in patients receiving dialysis: a
      randomized controlled trial.
AB  - CONTEXT: Patients receiving dialysis commonly experience malnutrition, reduced
      muscle mass (sarcopenia), and fatigue for which no effective treatment has been
      identified. Anabolic steroids are known to increase muscle mass and strength in
      healthy individuals, but their effect on the sarcopenia and fatigue associated
      with long-term dialysis has not been evaluated. OBJECTIVE: To assess the effects
      of an anabolic steroid, nandrolone decanoate, on lean body mass (LBM), functional
      status, and quality of life in dialysis patients. DESIGN: Randomized, double
      blind, placebo-controlled trial conducted between April 1996 and July 1997.
      SETTING: Hospital-based outpatient dialysis unit. PATIENTS: Twenty-nine patients
      undergoing dialysis for at least 3 months. INTERVENTION: Nandrolone decanoate,
      100 mg (n = 14), or placebo (n = 15) by intramuscular injection once a week for 6
      months. MAIN OUTCOME MEASURES: Weight, LBM, fatigue, grip strength, walking and
      stair-climbing times, and treadmill performance after 3 and 6 months of
      treatment. RESULTS: Lean body mass increased significantly in patients given
      nandrolone compared with patients given placebo (mean change [SD], +4.5 [2.3] kg;
      P<.001 compared with baseline). This effect was significantly greater than the
      change in LBM in the placebo group (mean change [SD], +1.9 [1.6] kg; P = .003
      compared with baseline; P = .005 compared with nandrolone group). Serum
      creatinine levels increased in the nandrolone group (+168 [203] mmol/L [1.9 [2.3]
      mg/dL]; P = .02) but not in the placebo group (-4.0 [177] mmol/L [0.04 [2.0]
      mg/dL]; P = .95), suggesting an increase in muscle mass. Time to complete the
      walking and stair-climbing test decreased from 36.5 to 32.7 seconds in the
      nandrolone group, while those in the placebo group increased from 38.7 to 42.1
      seconds (P = .05). Peak oxygen consumption increased in the individuals in the
      nandrolone group who performed treadmill tests, but not to a statistically
      significant degree. Grip strength did not change in either group. CONCLUSIONS:
      Treatment with nandrolone for 6 months resulted in a significant increase in LBM
      associated with functional improvement in patients undergoing dialysis.

PMID- 10208143
TI  - Resistance exercise and supraphysiologic androgen therapy in eugonadal men with
      HIV-related weight loss: a randomized controlled trial.
AB  - CONTEXT: Repletion of lean body mass (LBM) that patients lose in human
      immunodeficiency virus (HIV) infection has proved difficult. In healthy, HIV
      seronegative men, synergy between progressive resistance exercise (PRE) and very
      high-dose testosterone therapy has been reported for gains in LBM and muscle
      strength. OBJECTIVE: To determine whether a moderately supraphysiologic androgen
      regimen, including an anabolic steroid, would improve LBM and strength gains of
      PRE in HIV-infected men with prior weight loss and whether protease inhibitor
      antiretroviral therapy prevents lean tissue anabolism. DESIGN: Double-blind,
      randomized, placebo-controlled trial; post hoc analysis for effect of HIV
      protease inhibitor therapy conducted from January to October 1997. SETTING:
      Referral center in San Francisco, Calif. PATIENTS: Volunteer sample of 24
      eugonadal men with HIV-associated weight loss (mean, 9% body weight loss),
      recruited from an AIDS clinic and by referral and by advertisement. INTERVENTION:
      For 8 weeks, all subjects received supervised PRE with physiologic intramuscular
      testosterone replacement (100 mg/wk) to suppress endogenous testosterone
      production. Randomization was between an anabolic steroid, oxandrolone, 20 mg/d,
      and placebo. MAIN OUTCOME MEASURES: Lean body mass, nitrogen balance (10-day
      metabolic ward measurements), body weight, muscle strength, and androgen status.
      RESULTS: Twenty-two subjects completed the study (1 1 per group). Both groups
      showed significant nitrogen retention and increases in LBM, weight, and strength.
      The mean (SD) gains were significantly greater in the oxandrolone group than in
      the placebo group (5.6 [2.1] vs 3.8 [1.8] g of nitrogen per day [P=.05]; 6.9
      [1.7] vs 3.8 [2.9] kg of LBM [P=.005]; greater strength gains for various upper
      and lower body muscle groups by maximum weight lifted [P = .02-.05] and
      dynamometry [P = .01 -.05]). The mean (SD) high-density lipoprotein cholesterol
      level declined 0.25 (0.14) mmol/L (9.8 [5.4] mg/dL) significantly in the
      oxandrolone group (P < .001 compared with placebo). Results were similar whether
      or not patients were taking protease inhibitors. One subject in the oxandrolone
      group discontinued the study because of elevated liver function test results.
      CONCLUSIONS: A moderately supraphysiologic androgen regimen that included an
      anabolic steroid, oxandrolone, substantially increased the lean tissue accrual
      and strength gains from PRE, compared with physiologic testosterone replacement
      alone, in eugonadal men with HIV-associated weight loss. Protease inhibitors did
      not prevent lean tissue anabolism.

PMID- 10208144
TI  - Diabetes and decline in heart disease mortality in US adults.
AB  - CONTEXT: Mortality from coronary heart disease has declined substantially in the
      United States during the past 30 years. However, it is unknown whether patients
      with diabetes have also experienced a decline in heart disease mortality.
      OBJECTIVE: To compare adults with diabetes with those without diabetes for time
      trends in mortality from all causes, heart disease, and ischemic heart disease.
      DESIGN, SETTING, AND PARTICIPANTS: Representative cohorts of subjects with and
      without diabetes were derived from the First National Health and Nutrition
      Examination Survey (NHANES I) conducted between 1971 and 1975 (n = 9639) and the
      NHANES I Epidemiologic Follow-up Survey conducted between 1982 and 1984 (n =
      8463). The cohorts were followed up prospectively for mortality for an average of
      8 to 9 years. MAIN OUTCOME MEASURE: Changes in mortality rates per 1000 person
      years for all causes, heart disease, and ischemic heart disease for the 1982-1984
      cohort compared with the 1971-1975 cohort. RESULTS: For the 2 periods,
      nondiabetic men experienced a 36.4% decline in age-adjusted heart disease
      mortality compared with a 13.1% decline for diabetic men. Age-adjusted heart
      disease mortality declined 27% in nondiabetic women but increased 23% in diabetic
      women. These patterns were also found for all-cause mortality and ischemic heart
      disease mortality. CONCLUSIONS: The decline in heart disease mortality in the
      general US population has been attributed to reduction in cardiovascular risk
      factors and improvement in treatment of heart disease. The smaller declines in
      mortality for diabetic subjects in the present study indicate that these changes
      may have been less effective for people with diabetes, particularly women.

PMID- 10208145
TI  - Health-related quality of life as a predictor of mortality following coronary
      artery bypass graft surgery. Participants of the Department of Veterans Affairs
      Cooperative Study Group on Processes, Structures, and Outcomes of Care in Cardiac
      Surgery.
AB  - CONTEXT: Health-related quality of life has not been evaluated as a predictor of
      mortality following coronary artery bypass graft (CABG) surgery. Evaluation of
      health status as a mortality predictor may be useful for preoperative risk
      stratification. OBJECTIVE: To determine whether the Physical and Mental Component
      Summary scores from the preoperative Short-Form 36 (SF-36) health status survey
      predict mortality following CABG surgery after adjustment for known clinical risk
      variables. DESIGN: Prospective cohort study conducted between September 1992 and
      December 1996. SETTING: Fourteen Veterans Affairs hospitals. PATIENTS: Of the
      3956 patients undergoing CABG surgery only and who were enrolled in the
      Processes, Structures, and Outcomes of Care in Cardiac Surgery study, the 2480
      who completed a preoperative SF-36. MAIN OUTCOME MEASURE: All-cause mortality
      within 180 days after surgery. RESULTS: A total of 117 deaths (4.7%) occurred
      within 180 days of CABG surgery. The Physical Component Summary of the
      preoperative SF-36 was a statistically significant risk factor for 6-month
      mortality after adjustment for known clinical risk factors for mortality
      following CABG surgery. In multivariate analysis, a 10-point lower SF-36 Physical
      Component Summary score had an odds ratio (OR) of 1.39 (95% confidence interval
      [CI], 1.11-1.77; P=.006) for predicting mortality. The SF-36 Mental Component
      Summary score was not associated with 6-month mortality in multivariate analyses
      (OR, 1.09; 95% CI, 0.92-1.29; P=.31). CONCLUSIONS: The Physical Component Summary
      score from the preoperative SF-36 is an independent risk factor for mortality
      following CABG surgery. The baseline Mental Component Summary score does not
      appear to be predictive of mortality. Preoperative patient self-report of the
      physical component of health status may be helpful for risk stratification and
      clinical decision making for patients undergoing CABG surgery.

PMID- 10208146
TI  - Effects of writing about stressful experiences on symptom reduction in patients
      with asthma or rheumatoid arthritis: a randomized trial.
AB  - CONTEXT: Nonpharmacological treatments with little patient cost or risk are
      useful supplements to pharmacotherapy in the treatment of patients with chronic
      illness. Research has demonstrated that writing about emotionally traumatic
      experiences has a surprisingly beneficial effect on symptom reports, well-being,
      and health care use in healthy individuals. OBJECTIVE: To determine if writing
      about stressful life experiences affects disease status in patients with asthma
      or rheumatoid arthritis using standardized quantitative outcome measures. DESIGN:
      Randomized controlled trial conducted between October 1996 and December 1997.
      SETTING: Outpatient community residents drawn from private and institutional
      practice. PATIENTS: Volunteer sample of 112 patients with asthma (n = 61) or
      rheumatoid arthritis (n = 51) received the intervention; 107 completed the study,
      58 in the asthma group and 49 in the rheumatoid arthritis group. INTERVENTION:
      Patients were assigned to write either about the most stressful event of their
      lives (n = 71; 39 asthma, 32 rheumatoid arthritis) or about emotionally neutral
      topics (n = 41; 22 asthma, 19 rheumatoid arthritis) (the control intervention).
      MAIN OUTCOME MEASURES: Asthma patients were evaluated with spirometry and
      rheumatoid arthritis patients were clinically examined by a rheumatologist.
      Assessments were conducted at baseline and at 2 weeks and 2 months and 4 months
      after writing and were done blind to experimental condition. RESULTS: Of
      evaluable patients 4 months after treatment, asthma patients in the experimental
      group showed improvements in lung function (the mean percentage of predicted
      forced expiratory volume in 1 second [FEV1] improved from 63.9% at baseline to
      76.3% at the 4-month follow-up; P<.001), whereas control group patients showed no
      change. Rheumatoid arthritis patients in the experimental group showed
      improvements in overall disease activity (a mean reduction in disease severity
      from 1.65 to 1.19 [28%] on a scale of 0 [asymptomatic] to 4 [very severe] at the
      4-month follow-up; P=.001), whereas control group patients did not change.
      Combining all completing patients, 33 (47.1%) of 70 experimental patients had
      clinically relevant improvement, whereas 9 (24.3%) of 37 control patients had
      improvement (P=.001). CONCLUSION: Patients with mild to moderately severe asthma
      or rheumatoid arthritis who wrote about stressful life experiences had clinically
      relevant changes in health status at 4 months compared with those in the control
      group. These gains were beyond those attributable to the standard medical care
      that all participants were receiving. It remains unknown whether these health
      improvements will persist beyond 4 months or whether this exercise will prove
      effective with other diseases.

PMID- 10208147
TI  - Organizational characteristics of intensive care units related to outcomes of
      abdominal aortic surgery.
AB  - CONTEXT: Morbidity and mortality rates in intensive care units (ICUs) vary widely
      among institutions, but whether ICU structure and care processes affect these
      outcomes is unknown. OBJECTIVE: To determine whether organizational
      characteristics of ICUs are related to clinical and economic outcomes for
      abdominal aortic surgery patients who typically receive care in an ICU. DESIGN:
      Observational study, with patient data collected retrospectively and ICU data
      collected prospectively. SETTING: All Maryland hospitals that performed abdominal
      aortic surgery from 1994 to 1996. PATIENTS AND PARTICIPANTS: We analyzed hospital
      discharge data for patients in non-federal acute care hospitals in Maryland who
      had a principal procedure code for abdominal aortic surgery from January 1994
      through December 1996 (n = 2987). We obtained information about ICU
      organizational characteristics by surveying ICU medical directors at the 46
      Maryland hospitals that performed abdominal aortic surgery. Thirty-nine (85%) of
      the ICU directors completed this survey. MAIN OUTCOME MEASURES: In-hospital
      mortality and hospital and ICU length of stay. RESULTS: For patients undergoing
      abdominal aortic surgery, in-hospital mortality varied among hospitals from 0% to
      66%. In multivariate analysis adjusted for patient demographics, comorbid
      disease, severity of illness, hospital and surgeon volume, and hospital
      characteristics, not having daily rounds by an ICU physician was associated with
      a 3-fold increase in in-hospital mortality (odds ratio [OR], 3.0; 95% confidence
      interval [CI], 1.9-4.9). Furthermore, not having daily rounds by an ICU physician
      was associated with an increased risk of cardiac arrest (OR, 2.9; 95% CI, 1.2
      7.0), acute renal failure (OR, 2.2; 95% CI, 1.3-3.9), septicemia (OR, 1.8; 95%
      CI, 1.2-2.6), platelet transfusion (OR, 6.4; 95% CI, 3.2-12.4), and reintubation
      (OR, 2.0; 95% CI, 1.0-4.1). Not having daily rounds by an ICU physician, having
      an ICU nurse-patient ratio of less than 1:2, not having monthly review of
      morbidity and mortality, and extubating patients in the operating room were
      associated with increased resource use. CONCLUSIONS: Organizational
      characteristics of ICUs are related to differences among hospitals in outcomes of
      abdominal aortic surgery. Clinicians and hospital leaders should consider the
      potential impact of ICU organizational characteristics on outcomes of patients
      having high-risk operations.

PMID- 10208149
TI  - Is there a role for androgenic anabolic steroids in medical practice?

PMID- 10208148
TI  - Pharmacological treatment of alcohol dependence: a review of the evidence.
AB  - CONTEXT: Alcoholism affects approximately 10% of Americans at some time in their
      lives. Treatment consists of psychosocial interventions, pharmacological
      interventions, or both, but which drugs are most effective at enhancing
      abstinence and preventing relapse has not been systematically reviewed.
      OBJECTIVE: To evaluate the efficacy of 5 categories of drugs used to treat
      alcohol dependence--disulfiram, the opioid antagonists naltrexone and nalmefene,
      acamprosate, various serotonergic agents (including selective serotonergic
      reuptake inhibitors), and lithium. DATA SOURCES: Reports of randomized controlled
      trials, nonrandomized trials, and other study designs in English, French, and
      German identified from multiple searches of MEDLINE, EMBASE, and specialized
      databases; hand searching bibliographies of review articles; searches for
      unpublished literature; and discussions with investigators in the field. STUDY
      SELECTION: We included all studies on alcohol-dependent human subjects aged 18
      years or older from all inpatient and outpatient settings between 1966 and
      December 1997 that met our inclusion criteria. DATA EXTRACTION: We abstracted the
      following information: study design and blinding, diagnostic instrument and
      severity assessment, drug interventions and cointerventions, demographic and
      comorbidity details about patients, compliance, and numerous outcome measures
      (eg, relapse, return to drinking, drinking or nondrinking days, time to first
      drink, alcohol consumed per unit of time, craving). We graded quality of the
      individual articles (scale, 0-100) independently from the strength of evidence
      for each drug class (A, strong and consistent evidence of efficacy in studies of
      large size and/or high quality; B, mixed evidence of efficacy; C, evidence of
      lack of efficacy; and I, insufficient evidence). DATA SYNTHESIS: Of 375 articles
      evaluated, we abstracted and analyzed data from 41 studies and 11 follow-up or
      subgroup studies. Naltrexone (grade A) reduces the risk of relapse to heavy
      drinking and the frequency of drinking compared with placebo but does not
      substantially enhance abstinence, ie, avoidance of any alcohol consumption.
      Acamprosate (grade A, from large-scale studies in Europe) reduces drinking
      frequency, although its effects on enhancing abstinence or reducing time to first
      drink are less clear. Controlled studies of disulfiram (grade B) reveal a mixed
      outcome pattern--some evidence that drinking frequency is reduced but minimal
      evidence to support improved continuous abstinence rates. The limited data on
      serotonergic agents were not very promising (grade I), although most studies were
      confounded by high rates of comorbid mood disorders. Lithium lacks efficacy
      (grade C) in the treatment of primary alcohol dependence. CONCLUSIONS: Recent
      reports documenting that naltrexone and acamprosate are more effective than
      placebo in the treatment of alcoholism justify clinical interest in use of these
      medications for alcohol-dependent patients. Use of disulfiram is widespread but
      less clearly supported by the clinical trial evidence; however, targeted studies
      on supervised administration of disulfiram may be warranted. Use of existing
      serotonergic agents or lithium for patients with primary alcohol dependence does
      not appear to be supported by the efficacy data available at this time; these
      medications may still have a positive effect in patients with coexisting
      psychiatric disorders.

PMID- 10208150
TI  - Healing words: emotional expression and disease outcome.

PMID- 10208151
TI  - Reorganizing the delivery of intensive care may improve patient outcomes.

PMID- 10208153
TI  - JAMA patient page: alcohol.

PMID- 10208152
TI  - Outbreak of type A botulism and development of a botulism surveillance and
      antitoxin release system in Argentina.
AB  - CONTEXT: Botulism is an important public health problem in Argentina, but
      obtaining antitoxin rapidly has been difficult because global supplies are
      limited. In January 1998, a botulism outbreak occurred in Buenos Aires.
      OBJECTIVES: To determine the source of the outbreak, improve botulism
      surveillance, and establish an antitoxin supply and release system in Argentina.
      DESIGN, SETTING, AND PARTICIPANTS: Cohort study in January 1998 of 21 drivers of
      a specific bus route in urban Buenos Aires. MAIN OUTCOME MEASURE: Occurrence of
      botulism and implication of a particular food as the vehicle causing this
      outbreak. RESULTS: Nine (43%) of 21 bus drivers developed botulism, presenting
      with gastroenteritis, symptoms of acute cranial nerve dysfunction including
      ptosis, dysphagia, blurred vision, and motor weakness. One driver experienced
      respiratory failure. Type A toxin was detected from 3 of 9 patients' serum
      samples. All drivers received botulism antitoxin; there were no fatalities.
      Consumption of matambre (Argentine meat roll) was significantly associated with
      illness. Among 11 persons who ate matambre, 9 developed illness, compared with
      none of those who did not eat it (P<.001). The matambre had been cooked in water
      at 78 degrees C to 80 degrees C for 4 hours, sealed in heat-shrinked plastic
      wrap, and stored in refrigerators that did not cool adequately. Subsequently, a
      botulism surveillance and antitoxin release system was established. CONCLUSIONS:
      Insufficient cooking time and temperatures, storage in heat-shrinked plastic
      wrap, and inadequate refrigeration likely contributed to Clostridium botulinum
      spore survival, germination, and toxin production. A rapid-response botulism
      surveillance and antitoxin release system in Argentina should provide more timely
      distribution of antitoxin to patients and may serve as a model for other nations.

PMID- 10208154
TI  - Eighth International workshop on the fragile X syndrome and X-linked mental
      retardation, August 16-22, 1997.

PMID- 10208155
TI  - XLMR genes: update 1998.
AB  - Since the Seventh Fragile X and XLMR Mental Retardation (XLMR) Workshop in 1995,
      the genes for Coffin-Lowry, Mohr-Tranebjaerg, and Opitz G/BBB syndromes have been
      cloned. Jensen syndrome has been found to be allelic to Mohr-Tranebjaerg. Twenty
      new XLMR syndromes and metabolic or neuromuscular disorders have been reported.
      Twenty-four new localizations have been established, including five in previously
      reported conditions (FG, Carpenter, Arts, OPA2, and OFD1). The number of families
      with nonspecific XLMR that have been reported has continued to increase; 58
      families or loci are now known. Eighteen new families with nonspecific mental
      retardation (MRX) have been reported. Two of them, however, were subsequently
      found to have mutations in the RABGDIA gene, which codes for a GDP-dissociation
      inhibitor for RAB proteins. In total, 41 more entries have been added to the X
      chromosome map of XLMR. The total number of known syndromes and MRX families has
      increased to 178. Of the 120 known XLMR disorders, 53 have been mapped, and 22
      have been cloned. Assuming that at least 10 loci are necessary to account for the
      58 families with MRX, the total number of XLMR loci counted so far would be 130.
      Although it is likely that many of the disorders will eventually prove to be
      allelic, it is not possible at present to determine the precise number of loci
      for nonspecific XLMR.

PMID- 10208156
TI  - Synaptic synthesis of the Fragile X protein: possible involvement in synapse
      maturation and elimination.
AB  - Fragile X mental retardation syndrome results from the absence of or a defect in
      the protein (FMRP) encoded by the FMR1 gene. FMRP is found in dendrites and
      synapses as well as in the neuronal cell soma and nucleus, and although it is
      known to bind to RNA, the function of the protein in neurons is not known. We
      have studied activity-dependent changes in postsynaptically localized protein
      translation in central nervous system neurons. We find that FMRP is one of the
      proteins produced at synapses following stimulation of metabotropic glutamate
      receptors. We have also observed that Fragile X knockout mice, like human Fragile
      X patients, have excess numbers of long, thin, immature-appearing dendritic
      processes. Together, these findings suggest that FMRP plays a role in the process
      whereby synaptic activity during development results in structural and functional
      maturation of the synapse. We hypothesize that synaptic synthesis of FMRP may be
      essential for activity-based synapse maturation and elimination, a key process in
      normal brain development.

PMID- 10208157
TI  - Age-related language characteristics of children and adolescents with fragile X
      syndrome.
AB  - In addition to moderate-to-severe mental retardation (MR), the fragile X [fra(X)]
      mutation produces significant impediments in speech and language. Severe delays
      in speech and language have been demonstrated in both adult males and young
      individuals with the fra(X) mutation. Having observed longitudinal declines in IQ
      scores in young males with fra(X) and given the relationship between cognitive
      ability and language skill, we wanted to determine whether speech-language
      deficits in young males with fra(X) were age-related in ways comparable with
      those observed in cognitive deficits. We examined a small sample (n = 16) of
      children and adolescents, ages 6-17 years, using the Clinical Evaluation of
      Language Fundamental-Preschool (CELF-P). The CELF-P is used to evaluate language
      deficits in preschool children and assesses receptive and expressive language
      ability. It is standardized for children ages 3-7 years and provides age-normed
      standard scores. To evaluate changes in language scores, we converted raw scores
      into age-equivalents. Results indicate that males with fra(X) have significantly
      lower age equivalent scores compared with females. A cross-sectional analysis of
      males' age-equivalent scores reveals that a plateau is reached at approximately
      48 months. Our findings suggest that, as with IQ and adaptive behavior scores,
      language development in young, fully mutated fra(X) individuals appears to reach
      a plateau as they age.

PMID- 10208158
TI  - Longitudinal assessment of adaptive and maladaptive behaviors in fragile X males:
      growth, development, and profiles.
AB  - As young fully mutated fragile X [fra(X)] males age, cognitive levels (IQ scores)
      and adaptive behavior levels (DQ scores) decline. Given the variable behavioral
      profiles reported previously, we wondered whether changes in specific attributes
      of adaptive behavior are related to declines in composite adaptive behavior
      levels. We also examined maladaptive behavior to determine if changes are related
      to age. Therefore, we evaluated three areas of adaptive behavior, as well as
      maladaptive behavior, in 28 fully mutated fra(X) males, ages 4-14 years. To
      develop a profile of adaptive behavior, we analyzed nine subscale scores from the
      Vine-land Adaptive Behavior Scale (VABS). To assess maladaptive behavior, we
      graded part I of the VABS Maladaptive Behavior Scale. Subjects were sorted into
      three age cohorts, according to their initial test age: younger than 6 years; 6
      to 9 years; older than 9 years. Results indicate that, in all age groups, the
      communications domain is the most severely impacted compared with either the
      socialization domain or daily living skills and that, in all age groups, the
      socialization domain is a relative strength compared with either the
      communications domain or daily living skills. The youngest cohort manifested
      significant increases in age-equivalent community living skills. Significant
      differences in age-equivalent scores between cohorts were observed in written
      language and play skills. Maladaptive behavior scores were available from cross
      sectional data only. Twenty males (74%) showed significantly higher maladaptive
      scores than expected from other children their age. Our data analysis also
      revealed a moderate and significant negative correlation between maladaptive
      behavior levels and age (r = -0.54; P < 0.01). Curiously, adaptive and
      maladaptive behaviors did not correlate with each other.

PMID- 10208159
TI  - Psychometric assessment of families with X-linked mental retardation.
AB  - As part of an integrated approach to DNA-linkage analysis in X-linked mental
      retardation (XLMR), 29 members of five families suspected of having XLMR
      underwent psychometric assessment. Mental retardation was confirmed in all
      participants. The range of mental retardation varied from mild to profound within
      and between families. In addition, these preliminary results indicated family
      specific cognitive profiles in MRX45 and MRX46. The fact that two non-overlapping
      loci were involved provides strong evidence that specific cognitive profiles are
      linked to specific loci (genes) in mental retardation. We therefore recommend the
      application of standardised psychometric tests for the assessment of XLMR.

PMID- 10208161
TI  - Paternal nondisjunction in a 47,XY,fra(X)

PMID- 10208160
TI  - Electrodermal responses to sensory stimuli in individuals with fragile X
      syndrome: a preliminary report.
AB  - The fragile X mutation and fragile X syndrome are associated with hyperarousal,
      hyperactivity, aggression, and anxiety. These may be related to strong reactions
      to auditory, tactile, visual, and olfactory stimuli [Hagerman, 1996b; Hagerman
      and Cronister, 1996]. However, almost no data exist describing hyperarousal and
      sensory sensitivity in individuals with the fragile X mutation. This study
      establishes a reliable laboratory paradigm for examining reactions to sensory
      stimuli. We found the pattern of electrodermal responses (EDRs) to stimulation in
      one sensory modality predicted the pattern of EDRs in four other sensory systems.
      In addition, the EDR pattern of individuals with the fragile X mutation was
      related to their FMR-protein expression. Finally, EDRs in individuals with
      fragile X syndrome were significantly different from those of normal controls,
      demonstrating greater magnitude, more responses per stimulation, responses on a
      greater proportion of trials, and lower rates of habituation. The findings
      support the theory that individuals with fragile X syndrome have a
      physiologically based enhancement of reactions to sensations. Because
      electrodermal activity indexes sympathetic nervous system activity, the data
      suggest that the over-arousal to sensation may involve the sympathetic system.

PMID- 10208162
TI  - Maximizing the sensitivity of a screening questionnaire for determining Fragile X
      at-risk status.
AB  - Parents of 55 preschool and school-aged children with the FMR1 full mutation (fM)
      completed a brief screening questionnaire. Parents of 55 additional children,
      each of whom was individually matched for sex, age, and IQ to one of the 55
      children with Fragile X syndrome, also completed a questionnaire. Items on the
      questionnaire concerned behavior, rather than physical features or family
      history, associated with Fragile X syndrome. Children with the fM were more
      likely than controls to be on prescription medication, to have poor eye contact,
      to be described as nervous or anxious, and to regularly engage in repetitive
      movements and/or repetitive speech. Moreover, children with the fM received
      higher total scores on the questionnaire than their matched controls. These
      results suggest that questions about behavior are useful in the diagnostic
      evaluation of Fragile X syndrome, especially in the absence of the recognizable
      physical features associated with this condition.

PMID- 10208164
TI  - Heart rate variability and autonomic function during sleep in fragile X syndrome.

PMID- 10208163
TI  - Genotype, molecular phenotype, and cognitive phenotype: correlations in fragile X
      syndrome.
AB  - The study of the neurobehavioral consequences of mutations of FMR1, the gene
      responsible for fragile X syndrome (FraX), has been based largely on correlations
      between mutation patterns and cognitive profile. Following the characterization
      of FMRP, the FMR1 gene product, preliminary correlations between FMRP levels, and
      neurologic phenotype have been established. However, most of these investigations
      have focused on individuals at both ends of the genetic and cognitive spectra of
      FraX, subjects with normal or premutation (PM) alleles or males with the FMR1
      full mutation (FM). The present study is designed to characterize FMRP expression
      and to correlate it with IQ, in a sample representing a wide spectrum of FMR1
      mutations. For this purpose we developed a highly sensitive immunoblotting assay
      using peripheral leukocytes. Three distinct patterns of FMRP immunoreactivity (
      ir) emerged. Individuals with normal (n = 28) and PM (n = 8) alleles as well as
      most females with the FM (n = 14) showed the highest levels with multiple
      approximately 70-80 kDa FMRP-ir bands. Males with the FM (n = 10) demonstrated
      only a 70 kDa FMRP-ir band, and had significantly lower levels when compared with
      any previous groups. Males with mosaicism and three of 14 females with FM
      displayed a doublet with equal amounts of the highest and lowest molecular weight
      FMRP-ir bands. Multiple regression models that adjust for the effect of parental
      IQ indicated that both activation ratio and FMRP-ir are significantly correlated
      to subject IQ. We conclude that FMRP-ir offers promise as an indicator of the
      impact of FMR1 mutations upon neurologic function. Furthermore, our unexpected
      finding of FMRP-ir in all males with FM suggests that most of them are not
      transcriptionally silent.

PMID- 10208165
TI  - Dental maturity is advanced in Fragile X syndrome.
AB  - Fragile X (FraX) syndrome is the most common cause of inherited mental
      retardation. The FraX gene (FMR1) has been cloned, and the mutation causing the
      disease is now known. We estimated the effect of FraX on dental development in 28
      affected boys (aged 4.9-17.6 years) and three carrier girls (aged 5.8, 10.4, and
      12.7 years). Dental maturity, assessed on the basis of formation [Demirjian A,
      Goldstein H. 1976: Ann Hum Biol 3:411-421] and of emergence [Hagg U, Taranger J.
      1985: Angle Orthod 55:93-107], was compared with growth in stature and skeletal
      maturity. The mean relative dental age was advanced in FraX males, based on
      formation (+1.4 SD) and on emergence (+1.1 SD). More pronounced advancement was
      seen in younger children. Dental maturity was advanced in heterozygous carrier
      girls as well. Height and skeletal maturity did not show a similar trend toward
      advanced development.

PMID- 10208166
TI  - Deletion of 8.5 Mb, including the FMR1 gene, in a male with the fragile X
      syndrome phenotype and overgrowth.
AB  - A four-year-old boy with severe psychomotor retardation, facial appearance
      consistent with the fragile X syndrome, hypotonia, and overgrowth was found to
      have a deletion including the fragile X gene (FMR1). The breakpoints of the
      deletion were established between CDR1 and sWXD2905 (approximately 200 kb apart)
      at Xq27.1 (centromeric) and between DXS8318 (612-1078L) and DXS7847 (576-291L)
      (approximately 250 kb apart) at Xq28, about 500 kb telomeric to the FMR1 gene.
      The total length of the deletion is approximately 8.5 Mb. The propositus's
      mother, who was found to be a carrier of the deletion, showed very mild mental
      impairment. Except for mental retardation, which is a common finding in all cases
      reported with similar deletions of chromosome Xq, this patient had generalized
      overgrowth, exceeding the 97th centile for height and weight. Obesity and
      increased growth parameters have been reported in other patients with deletions
      either overlapping or within a distance of 0.5 Mb from the deletion in the
      present patient. Thus, it is suggested that a deletion of the 8-Mb fragment
      centromeric to the FMR1 gene might have an effect on growth.

PMID- 10208167
TI  - Longitudinal changes in cognitive and adaptive behavior in fragile X females: a
      prospective multicenter analysis.
AB  - In prospective studies of young, fragile X [fra(X)] males with the full mutation,
      cognitive abilities (IQ scores) and adaptive behavior levels (DQ scores) declined
      in most subjects tested. Little is known about longitudinal changes in IQ and DQ
      scores in young fra(X) females, although one earlier retrospective study showed
      declines in IQ scores in 8 of 11 subjects. To examine fra(X) females
      prospectively, we tested and retested 13 females with the full mutation, age 4 to
      15 years. Nine were tested and retested in North America, and four were evaluated
      at the Catholic University in Leuven, Belgium. Cognitive abilities of North
      American females were measured using the Stanford-Binet 4th Edition. Adaptive
      behavior levels were ascertained from the Vineland Adaptive Behavior Scales. For
      Belgians, test-retest scores from the Wechsler Intelligence Scales for Children
      Revised were used. Subjects were subsequently separated into two age cohorts:
      those tested initially before age 7 years and those tested initially after age 7
      years. Compared with young males with the full mutation and of the same age,
      females expectedly display a wider range of IQ scores. Test-retest IQ scores
      showed statistically significant decreases (P < 0.03). Analysis of individual
      test-retest scores indicate that declines in eight females were statistically
      significant. Adaptive behavior scores were available only for North American
      females. Five of nine (55%) showed significant declines in DQ. Like young males
      with the full mutation, all females with the full mutation attained higher
      adaptive behavior levels than cognitive scores, i.e., DQ > IQ.

PMID- 10208168
TI  - Fragile X syndrome and selective mutism.
AB  - This is the first report that details an association between fragile X syndrome
      (FXS) and selective mutism (SM). This 12-year-old girl with heterozygous full
      mutation at FMR1 has a long history of social anxiety and shyness in addition to
      SM. Her sister also has the full mutation and a history of SM that resolved in
      adolescence. A beneficial response to fluoxetine and psychotherapy is described.
      The FMR1 mutation appears to be the first gene mutation associated with SM and
      further studies are recommended to assess what percentage of patients with SM
      have the FMR1 mutation.

PMID- 10208169
TI  - Compound heterozygous female with fragile X syndrome.
AB  - We report on a 15-year-old compound heterozygous young woman with fragile X
      syndrome who has a full mutation of 363 repeats on one X chromosome and a
      premutation of 103 repeats on the other X chromosome. As predicted, subsequent
      testing demonstrated that her father carries a premutation (98 repeats) as does
      her mother (146 repeats). There is only one previous report of a compound
      heterozygous female with fragile X syndrome. By quantitation of Southern blot
      signals, the activation ratio for the premutation (the proportion of the
      premutation on the active X chromosome) was determined to be 0.78.
      Immunocytochemistry of blood smears showed fragile X mental retardation-1 protein
      (FMRP) expression in 63.5% of lymphocytes. Cognitively, this woman is functioning
      in the mid-range of involvement for fragile X females. She attends regular
      classes and receives supplemental assistance for her learning disabilities. She
      experiences behavior characteristics typical of females with fragile X syndrome
      including severe shyness, anxiety, panic episodes, mood swings, and attention
      deficits. She has responded very well to appropriate treatment including
      fluoxetine for anxiety, methylphenidate for attentional problems, and educational
      therapy.

PMID- 10208171
TI  - Twinning and premature ovarian failure in premutation fragile X carriers.

PMID- 10208170
TI  - Fragile X premutation is a significant risk factor for premature ovarian failure:
      the International Collaborative POF in Fragile X study--preliminary data.
AB  - The preliminary results of an international collaborative study examining
      premature menopause in fragile X carriers are presented. A total of 760 women
      from fragile X families was surveyed about their fragile X carrier status and
      their menstrual and reproductive histories. Among the subjects, 395 carried a
      premutation, 128 carried a full mutation, and 237 were noncarriers. Sixty-three
      (16%) of the premutation carriers had experienced menopause prior to the age of
      40 compared with none of the full mutation carriers and one (0.4%) of the
      controls. Based on these preliminary data, there is a significant association
      between fragile X premutation carrier status and premature menopause.

PMID- 10208172
TI  - Menstrual disorders and endocrine profiles in fragile X carriers prior to 40
      years of age: a pilot study.
AB  - This prospective study reports serum hormone measurements associated with
      menopause in fragile X carriers (n = 9, age between 31-40 years). These results
      demonstrate the occurrence of premature ovarian failure.

PMID- 10208173
TI  - FMR1 repeat analysis in patients with ovarian dysfunction or failure.

PMID- 10208174
TI  - Ultrastructure of the fragile X chromosome: new observations on the fragile site.
AB  - Using a nonair-drying modification of a method for longitudinal sectioning of
      metaphase spreads on glass slides [Wen et al., 1997], we have studied 14
      preidentified X chromosomes (10 from fragile X specimens and 4 controls) with
      transmission electron microscopy (TEM). Four of 10 X chromosomes from fragile X
      specimens exhibited lighter chromatin density in the area of and distal to the
      fragile site, most pronounced under dark-field TEM. A clear line of separation at
      the fragile site locus was also observed by TEM in an X chromosome with no
      visible fragile site after Q-banding. We hypothesize that these areas of lighter
      density, including lines of separation, precede the appearance of the fragile
      site that is commonly observed using light microscopy.

PMID- 10208175
TI  - First transmission electron micrograph of continuous mitotic spindle fibers
      between polar area and chromosome ends.

PMID- 10208176
TI  - Accelerated prenatal diagnosis of fragile X syndrome by polymerase chain reaction
      restriction fragment detection.
AB  - Prenatal diagnosis of fragile X syndrome requires detection of the full FMR1
      mutation in chorionic villus or amniotic fluid cell samples. Although analysis of
      genomic DNA restriction fragment pattern is a highly reliable technique for
      identification of the full FMR1 mutation, standard Southern blot determination of
      this pattern requires significantly more genomic DNA than is initially available
      from a prenatal sample. To overcome this limitation we developed a method that
      determines the diagnostic pattern of genomic restriction fragments from a
      fraction of a prenatal specimen. The prenatal DNA sample is first digested with
      EcoRI and EagI, and after agarose gel electrophoresis, the 2- to 10-kb region of
      the gel is serially sectioned and amplified by polymerase chain reaction.
      Analysis of prenatal samples from an unaffected male and from a full mutation
      male showed that this approach generated a diagnostic pattern comparable with a
      Southern blot of 100-fold more material. This innovation enables laboratories to
      prenatally diagnose the full FMR1 mutation sooner than standard techniques.

PMID- 10208178
TI  - DNA panel for interlaboratory standardization of haplotype studies on the fragile
      X syndrome and proposal for a new allele nomenclature.

PMID- 10208177
TI  - Prenatal fragile X detection using cytoplasmic and nuclear-specific monoclonal
      antibodies.
AB  - We have been carrying out studies aimed at improving prenatal detection of the
      fragile X chromosome/mutation. Our current protocol requires a turnaround time
      (TAT) of several days. In an attempt to reduce the TAT, we have turned to the use
      of monoclonal antibodies (mAbs). Monoclonal antibody 1A1 (provided by Dr. Mandel
      of INSERM) immunostaining was performed according to a modified three-step
      immunocytochemical procedure. We found that cytoplasmic staining intensities,
      using mAb 1A1/avidin biotinylated complex/diaminobenzidine, varied from light to
      heavy within each sample, with controls exhibiting a majority of heavily stained
      cells in both chorionic villus (CV) sample and amniotic fluid cultured cells.
      Using mAb 1A1 and a new nuclear-specific antibody, mAb 3F11, we found that CV
      cultured cells harboring the FMR1 full mutation could be distinguished from
      controls as early as 10 weeks of gestation in both male and female specimens.
      Western blot analysis showed that the antibodies have similar staining patterns
      but that mAb 3F11 has fewer background/nonspecific bands. Our results demonstrate
      that it is feasible to detect fragile X full mutations within one day after
      obtaining cells from CV specimens taken as early as 10 weeks of gestation.

PMID- 10208179
TI  - Molecular screening for fragile X syndrome among Indonesian children with
      developmental disability.

PMID- 10208180
TI  - A dentist's office is the template for medicine.

PMID- 10208181
TI  - Emergency department care of the asthma patient: predicting "bounce-back"
      patients.

PMID- 10208182
TI  - Bronchodilator therapy in status asthmaticus.

PMID- 10208183
TI  - Bronchial artery embolotherapy for control of acute hemoptysis: analysis of
      outcome.

PMID- 10208184
TI  - Video-assisted endoscopy, not just endoscopy, for percutaneous dilatational
      tracheostomy.

PMID- 10208185
TI  - Not a matter of life and death!

PMID- 10208186
TI  - Point-of-care blood testing: more than simply changing venue.

PMID- 10208187
TI  - Prospective multicenter study of relapse following treatment for acute asthma
      among adults presenting to the emergency department. MARC investigators.
      Multicenter Asthma Research Collaboration.
AB  - STUDY OBJECTIVE: To identify factors associated with relapse following treatment
      for acute asthma among adults presenting to the emergency department (ED).
      DESIGN: Prospective inception cohort study performed during October 1996 to
      December 1996 and April 1997 to June 1997, as part of the Multicenter Asthma
      Research Collaboration. SETTING: Thirty-six EDs in 18 states. PATIENTS: ED
      patients, aged 18 to 54 years, with physician diagnosis of acute asthma. For the
      present analysis, we restricted the cohort to patients sent home from the ED (n =
      971), then further excluded patients with comorbid respiratory conditions (n =
      32). This left 939 eligible subjects to have follow-up data. INTERVENTIONS: None.
      MEASUREMENTS AND RESULTS: Two weeks after being sent home from the ED, patients
      were contacted by telephone. A relapse was defined as an urgent or unscheduled
      visit to any physician for worsening asthma symptoms during the 14-day follow-up
      period. Complete follow-up data were available for 641 patients, of whom 17%
      reported relapse (95% confidence interval, 14 to 20). There was no significant
      difference in peak expiratory flow rate (PEFR) between patients who suffered
      relapse and those who did not. In a multivariate logistic regression analysis
      (controlling for age, gender, race, and primary care provider status), patients
      who suffered relapse were more likely to have a history of numerous ED (odds
      ratio [OD] 1.3 per 5 visits) and urgent clinic visits (OR 1.4 per 5 visits) for
      asthma in the past year, use a home nebulizer (OR 2.2), report multiple triggers
      of their asthma (OR 1.1 per trigger), and report a longer duration of symptoms
      (OR 2.5 for 1 to 7 days). CONCLUSION: Among patients sent home from the ED
      following acute asthma therapy, 17% will have a relapse and PEFR does not predict
      who will develop this outcome. By contrast, several historical features were
      associated with increased risk. Further research should focus on ways to decrease
      the relapse rate among these high-risk patients. The clinician may wish to
      consider these historical factors when making ED decisions.

PMID- 10208188
TI  - Incidence and prevalence of asthma among adult Finnish men and women of the
      Finnish Twin Cohort from 1975 to 1990, and their relation to hay fever and
      chronic bronchitis.
AB  - STUDY OBJECTIVES: To examine the prevalence of asthma and hay fever, and the
      incidence and temporal relationships of asthma, hay fever, and chronic bronchitis
      among adult twins during a 15-year period. DESIGN: Prospective cohort study.
      PARTICIPANTS: A population of 11,540 Finnish adult men and women, initially 18 to
      45 years of age, who returned a health questionnaire in 1975, 1981, and 1990 as
      part of the Finnish Twin Cohort study. METHODS: Age-standardized prevalences and
      cumulative incidences among individuals were calculated for asthma, hay fever,
      and chronic bronchitis. The incidence of asthma among subjects with and without
      hay fever or chronic bronchitis was analyzed in the entire cohort as well as in
      twin pairs discordant for incident asthma. RESULTS: The prevalence of asthma
      increased slightly from 1975 (2.0% in men and 2.2% in women) to 1990 (2.9% in men
      and 3.1% in women). The prevalence of hay fever showed a larger increase in men
      and women (from 6.8% and 9.8% to 11.8% and 15.3%, respectively). Compared with
      figures for 1976 to 1981, no significant increase in asthma incidence occurred
      from 1982 to 1990, whereas the incidence of hay fever was lower during the latter
      period among men (incidence rate ratio, 0.7; 95% confidence interval, 0.6 to 0.9)
      as was the incidence of chronic bronchitis among women (incidence rate ratio,
      0.7; 95% confidence interval, 0.6 to 0.9). Hay fever and chronic bronchitis were
      usually diagnosed before asthma. Both diseases increased the risk of asthma
      significantly on the basis of analyses of all individuals and of discordant twin
      pairs. CONCLUSIONS: The pattern of increase in asthma and hay fever prevalence
      with time was similar, and hay fever was a strong predictor of asthma. These
      diseases showed no significant increase in incidence.

PMID- 10208189
TI  - Effect of continuously nebulized ipratropium bromide plus albuterol on emergency
      department length of stay and hospital admission rates in patients with acute
      bronchospasm. A randomized, controlled trial.
AB  - OBJECTIVE: To compare the outcome of patients with acute bronchospasm treated
      with continuously nebulized albuterol plus ipratropium bromide vs albuterol
      alone. SETTING: The Emergency Department (ED) at the University of California San
      Francisco Medical Center. PARTICIPANTS: Patients > or = 18 years old presenting
      to the ED with acute bronchospasm and a peak expiratory flow rate (PEFR) of < 70%
      predicted. INTERVENTIONS: This was a prospective, randomized, double-blind,
      placebo-controlled trial. Subjects were treated with either a combination of
      albuterol (10 mg/h) plus ipratropium bromide (1.0 mg/h) or albuterol alone via
      continuous nebulization for a maximum of 3 h. Vital signs, Borg dyspnea score,
      and PEFR were recorded hourly. Primary outcome measures were improvement in PEFR,
      hospital admission rates, and length of stay in the ED. MEASUREMENTS AND RESULTS:
      Data was analyzed for 67 subjects. The mean age (-/+ SD) was 47.5+/-18.8, and
      mean initial PEFR was 44.8+/-12.5% of predicted. The median length of stay for
      all subjects was 225 min, and 31% of all subjects were admitted. Patients given
      combination therapy averaged 6.3% greater improvement in PEFR compared with
      control subjects (95% confidence interval [CI], -15% to 27%. The odds ratio for
      admission with combination therapy was 0.88 (95% CI, 0.28 to 2.8). The median
      length of stay in the ED was 35 min shorter for those receiving combination
      treatment (210 vs 245 min; p = 0.03). However, when adjusted for initial PEFR,
      there was no statistically significant difference (p = 0.26). CONCLUSION:
      Although the direction of all three outcome measures favored combination therapy,
      there was no statistically significant difference between ED patients with acute
      bronchospasm receiving continuous albuterol plus ipratropium bromide and those
      receiving albuterol alone.

PMID- 10208190
TI  - Safety of long-term treatment with HFA albuterol.
AB  - BACKGROUND: Chlorofluorocarbons (CFCs) used as propellants in metered-dose
      inhalers deplete stratospheric ozone, which results in serious public health
      concerns. Albuterol has been reformulated in the non-ozone-depleting propellant,
      hydrofluoroalkane-134a (HFA albuterol). OBJECTIVES: The primary objective was to
      compare the safety of HFA albuterol to an albuterol product formulated in
      chlorofluorocarbon propellants (CFC albuterol) during 1 year of treatment in
      asthmatics. Bronchodilator efficacy of the two products was assessed as a
      secondary objective. METHODS: The results from two open-label, parallel-group
      trials of similar design in asthmatics requiring short-acting beta-agonists for
      symptom control were combined. Patients took two puffs bid of either HFA
      albuterol or CFC albuterol for 1 year. Additional puffs of study drug were
      allowed as needed to control asthma symptoms. Adverse events were recorded at
      clinic visits. Patients self-administered study drug at quarterly visits and
      underwent serial spirometry during a 6-h period postdose. Bronchodilator efficacy
      variables, based on FEV1 response to study drug, were proportion of responders,
      time to onset of effect, peak percent change, time to peak effect, duration of
      effect, and area under the curve. Differences between products and changes over
      time in efficacy variables were assessed using an analysis of variance model.
      Regression analyses with FEV1 as a covariate were performed post-hoc to analyze
      changes in bronchodilator efficacy over time. RESULTS: Demographic and baseline
      characteristics were similar for patients receiving HFA albuterol (n = 337) and
      CFC albuterol (n = 132). Total reported adverse events were similar for the two
      treatments. Differences in only four individual adverse events were noted: the
      HFA albuterol group reported more gastroenteritis and dizziness; the CFC
      albuterol group reported more epistaxis and expectoration. Adverse events
      attributed to study drug use were infrequent. No serious adverse events were
      related to study drug use. Predose FEV1 at quarterly visits increased to a small
      extent in both groups from month 0 to month 12. The bronchodilator efficacy of
      HFA albuterol was comparable to that of CFC albuterol at the quarterly visits,
      but decreased from baseline for both products over the 12 months of treatment.
      Use of inhaled corticosteroids, nasal corticosteroids, or theophylline did not
      explain the increase in predose FEV1 over time and did not protect patients from
      developing reduced bronchodilator efficacy by month 12. The change in predose
      FEV1 did not entirely account for the reduced bronchodilator efficacy over time.
      CONCLUSIONS: HFA albuterol has a safety profile similar to that of CFC albuterol
      during chronic, scheduled use, and both drugs are well tolerated. HFA albuterol
      and CFC albuterol provided comparable bronchodilator efficacy, but bronchodilator
      efficacy decreased for both products with 1 year of use.

PMID- 10208191
TI  - Clickhaler (a novel dry powder inhaler) provides similar bronchodilation to
      pressurized metered-dose inhaler, even at low flow rates.
AB  - STUDY OBJECTIVE: Comparison of the bronchodilator response to an albuterol novel
      dry powder inhaler (DPI) (Clickhaler [CH]; ML Laboratories PLC; St. Albans, UK)
      activated at various inspiratory flow rates and to an albuterol pressurized
      metered-dose inhaler (pMDI) by patients with moderate to moderately severe stable
      asthma. DESIGN: Randomized, double-blind, placebo-controlled comparison of the
      bronchodilator response to albuterol DPI (200 microg) at inspiratory flow rates
      of approximately 15, 30, and 60 L/min in patients with stable asthma with
      demonstrated reversibility to albuterol. Active (albuterol via pMDI inhaled at 30
      L/min) and placebo controls were included. SETTING: Single center study at the
      chest/allergy unit of a teaching hospital in Canada. PATIENTS: Sixteen patients
      with moderate to moderately severe stable asthma. MEASUREMENTS AND RESULTS:
      Efficacy end points were FEV1, FVC, FEV1/FVC, maximum expiratory flow, and forced
      expiratory flow between 25% and 75% of vital capacity. Safety end points included
      heart rate, BP, and tremor. There was no significant difference between the
      bronchodilator response to albuterol via the CH at 15, 30, and 60 L/min
      inspiratory flow rate and, at all flow rates, no significant difference was found
      comparing albuterol CH with the pMDI. All of the techniques for delivering
      albuterol provided significantly better bronchodilatation than placebo. Adverse
      events were minimal and did not differ between CH and pMDI or between the various
      flow rates inhaled through the CH. CONCLUSION: A novel passive albuterol DPI (CH)
      provides a similar bronchodilator response at 15, 30, and 60 L/min inspiratory
      flow rates compared with a pMDI used optimally.

PMID- 10208193
TI  - The combination of ipratropium and albuterol optimizes pulmonary function
      reversibility testing in patients with COPD.
AB  - STUDY OBJECTIVES: To determine whether the combination of ipratropium bromide and
      albuterol results in greater and more consistent pulmonary function test (PFT)
      response rates than ipratropium bromide or albuterol alone in patients with COPD.
      DESIGN: Retrospective review of two recently completed 3-month, randomized,
      double-blind, parallel, multicenter, phase III trials. SETTING: Outpatient.
      PATIENTS: A total of 1,067 stable patients with COPD. INTERVENTIONS: Ipratropium
      bromide (36 microg qid), albuterol base (180 microg qid), or an equivalent
      combination of ipratropium bromide and albuterol sulfate (42 microg and 240
      microg qid, respectively). MEASUREMENTS AND RESULTS: PFT response rates were
      analyzed using 12% and 15% increases in FEV1 compared with baseline values and
      were measured in the various treatment groups on days 1, 29, 57, and 85 in these
      trials. Regardless of whether a 12% or a 15% increase in FEV1 was used to define
      a positive response, an equivalent combination of ipratropium bromide and
      albuterol sulfate was superior to the individual agents (p < 0.05; all
      comparisons within 30 min). In addition, a 15% or more increase in FEV1 was seen
      in > 80% of patients who received the combination of ipratropium and albuterol
      sulfate during the initial PFT and continued to be observed 3 months after
      initial testing. CONCLUSIONS: Use of a combination of ipratropium bromide and
      albuterol sulfate is superior to the individual agents in identifying PFT
      reversibility in patients with COPD.

PMID- 10208192
TI  - Efficacy of salmeterol xinafoate in the treatment of COPD.
AB  - STUDY OBJECTIVES: To examine and compare the efficacy and safety of salmeterol
      xinafoate, a long-acting inhaled beta2-adrenergic agonist, with inhaled
      ipratropium bromide and inhaled placebo in patients with COPD. DESIGN: A
      stratified, randomized, double-blind, double-dummy, placebo-controlled, parallel
      group clinical trial. SETTING: Multiple sites at clinics and university medical
      centers throughout the United States. PATIENTS: Four hundred eleven symptomatic
      patients with COPD with FEV1 < or = 65% predicted and no clinically significant
      concurrent disease. INTERVENTIONS: Comparison of inhaled salmeterol (42 microg
      twice daily), inhaled ipratropium bromide (36 microg four times a day), and
      inhaled placebo (2 puffs four times a day) over 12 weeks. RESULTS: Salmeterol
      xinafoate was significantly (p < 0.0001) better than placebo and ipratropium in
      improving lung function at the recommended doses over the 12-week trial. Both
      salmeterol and ipratropium reduced dyspnea related to activities of daily living
      compared with placebo; this improvement was associated with reduced use of
      supplemental albuterol. Analyses of time to first COPD exacerbation revealed
      salmeterol to be superior to placebo and ipratropium (p < 0.05). Adverse effects
      were similar among the three treatments. CONCLUSIONS: These collective data
      support the use of salmeterol as first-line bronchodilator therapy for the long
      term treatment of airflow obstruction in patients with COPD.

PMID- 10208194
TI  - Criteria for outpatient management of proximal lower extremity deep venous
      thrombosis.
AB  - STUDY OBJECTIVES: To develop and to evaluate selection criteria for outpatient
      management of deep venous thrombosis (DVT). DESIGN: We developed outpatient
      treatment eligibility criteria that incorporated demographic and clinical data.
      We aimed to exclude patients at high risk for bleeding or recurrent clotting, as
      well as those with pulmonary embolism, limited cardiopulmonary reserve, or need
      for hospitalization due to another illness. Then, we retrospectively applied the
      criteria to hospitalized patients with newly diagnosed proximal lower extremity
      DVT to determine the fraction of patients eligible for outpatient therapy;
      patients were classified as eligible, possibly eligible, or ineligible for home
      treatment based on the selection criteria. SETTING: University hospital.
      PATIENTS: One hundred ninety-five hospitalized patients diagnosed as having
      proximal lower extremity DVT by duplex ultrasound over a 1-year period.
      MEASUREMENTS: Frequency of complications during initial DVT therapy, including
      major bleeding, symptomatic thromboembolism, and death. RESULTS: Eighteen (9%)
      patients were classified as eligible, and 18 (9%) were classified as possibly
      eligible for outpatient therapy. None of these patients developed complications.
      Of the 159 (82%) patients classified as ineligible, 13 (8%; 95% confidence
      interval [CI], 4 to 12%) died or developed serious complications. Therefore, the
      eligibility criteria had a sensitivity of 100% (95% CI, 92 to 100%) and a
      negative predictive value of 100% (95% CI, 92 to 100%) for predicting serious
      complications. CONCLUSIONS: Specific eligibility criteria may identify a subset
      of patients with acute DVT who can be treated safely at home.

PMID- 10208195
TI  - Frequency of pulmonary embolism in patients with low-probability lung scan and
      negative lower extremity venous ultrasound.
AB  - STUDY OBJECTIVES: To define the prevalence of pulmonary embolism (PE) in patients
      who are undergoing pulmonary arteriography because of a high clinical suspicion
      for PE but who have had a low-probability lung scan and a negative lower
      extremity venous ultrasound examination. DESIGN: A retrospective review of the
      medical records of 365 consecutive patients who underwent pulmonary arteriograms
      for suspected PE was undertaken. RESULTS: Of the 365 pulmonary arteriograms, 62
      were performed in patients with suspected PEs despite a low-probability lung scan
      and a negative lower extremity venous ultrasound examination. In the latter
      group, five patients (8%; 95% confidence interval, 2.7% to 18%) had PEs revealed
      on the arteriogram. CONCLUSIONS: In patients whose presentation provokes a high
      clinical suspicion for PE despite having had a low-probability lung scan, a
      negative lower extremity venous ultrasound examination is insufficient to
      preclude proceeding to pulmonary angiography.

PMID- 10208196
TI  - The effects of erythromycin on the electrocardiogram.
AB  - BACKGROUND: Various cardiac electrophysiologic effects have been attributed to
      erythromycin. During the course of treating a pneumonia patient with IV
      erythromycin, the conversion of atrial fibrillation to a sinus rhythm, and its
      subsequent reversal, appeared to be causally related to the introduction and
      cessation of this antibiotic. OBJECTIVE: This observation suggested the need for
      studying the changes in the ECG following the use of IV erythromycin in a typical
      clinical setting. DESIGN: A prospective comparative drug study. SETTING: A
      university-affiliated teaching hospital. PATIENTS: Nineteen patients being
      treated for uncomplicated community-acquired pneumonia. INTERVENTION: IV
      erythromycin, 500 mg, and/or IV cefuroxime, 750 mg, infused in 250 mL of saline
      over 20 min. In the 11 patients who were receiving both of the antibiotics,
      cefuroxime was administered immediately before erythromycin was infused.
      MEASUREMENTS: The 12-lead ECG measurements were obtained before infusion, at 5
      min intervals during each infusion, and at 5 and 10 min after the infusions had
      been completed. All of the ECG complexes and intervals were measured using a
      software program (Interpretive Cardiograph; Hewlett Packard; Palo Alto, CA).
      RESULTS: The administration of IV erythromycin increased heart rate and prolonged
      the corrected QT (QTc) interval. These changes were significant at 15 min of the
      infusion, and were no longer evident 5 min after the infusion had been stopped.
      The administration of IV cefuroxime did not produce any ECG changes. CONCLUSIONS:
      A single, standard dose of IV erythromycin prolongs the QTc interval; therefore,
      the drug should always be administered as a slow infusion. ECG monitoring should
      accompany erythromycin therapy in critically ill patients, in patients with
      electrolyte disorders, or in patients taking other drugs with similar cardiac
      effects.

PMID- 10208197
TI  - Routine intraoperative angiography improves the early patency of coronary grafts
      performed on the beating heart.
AB  - OBJECTIVES: The techniques of performing coronary revascularization without
      cardiopulmonary bypass are rapidly evolving. However, concern remains regarding
      the accuracy of coronary artery anastomoses performed on the beating heart. This
      report reviews the use of intraoperative angiography in the critical appraisal of
      "off-pump" coronary artery bypass graft (CABG) surgery. PATIENTS: Intraoperative
      angiography was performed in 24 consecutive patients undergoing CABG surgery
      without cardiopulmonary bypass. In all, 24 left internal mammary artery (LIMA)
      grafts and 18 saphenous vein bypass grafts were assessed for patency, anastomosis
      quality, distal and proximal runoff, and correct placement. RESULTS: All of the
      saphenous vein-to-coronary artery anastomoses were widely patent, although two
      patients (8%) required revision of their LIMA grafts on the basis of angiographic
      findings. CONCLUSION: Intraoperative angiography permits the surgeon to
      immediately appraise the CABG and to revise, if necessary, any graft abnormality,
      thus potentially eliminating the need for early repeated surgery. The practice of
      routine intraoperative angiography is likely to improve the outcome of CABG
      surgery on the beating heart.

PMID- 10208198
TI  - A comparative analysis of arranging in-flight oxygen aboard commercial air
      carriers.
AB  - INTRODUCTION: As air travel has become more commonplace in today's society, so
      too has air travel by oxygen-using individuals. Because there is little oversight
      or standardization of in-flight oxygen by the Federal Aviation Administration,
      individual airlines' policies and practices may vary greatly. On the premise that
      such variation may cause confusion by prospective air travelers, we undertook the
      current study to describe individual air carriers' policies and practices and to
      provide guidance to future air travelers. METHODS: Data were collected by a
      series of telephone calls placed by the study investigators to all commercial air
      carriers listed in the 1997 Cleveland Metropolitan Yellow Pages. The callers were
      registered respiratory therapists who identified themselves as inexperienced
      oxygen-requiring travelers wishing to arrange in-flight oxygen for an upcoming
      trip. Standard questions were asked of each carrier that included the following:
      Did the carrier have a special "help desk" to assist with oxygen arrangements?
      What oxygen systems, liter flow options, and interface devices were available?
      What was the charge for oxygen? How was the charged determined? What
      documentation from the physician was required? How much notification was required
      by the airline before the actual flight? In addition to recording these
      responses, the total amount of time spent on the telephone by the caller was
      logged along with the number of telephone calls and number of people spoken to in
      arranging in-flight oxygen. To compare oxygen charges between airlines, we
      calculated charges based on a "standard trip," which was defined as a nonstop,
      round-trip lasting 6 h in which the traveler used a flow rate of 2 L/min.
      RESULTS: Of the 33 commercial air carriers listed in the directory, 11 were US
      based carriers and 22 were international-based carriers. Seventy-six percent of
      the airlines offered in-flight oxygen. For the 25 carriers offering in-flight
      oxygen, mean phone time required to make the arrangements was 9.96+/-4.8 min
      (range, 3 to 20 min). No more than two telephone calls were required to make
      oxygen arrangements. Most carriers required 48- to 72-h advance notice, with a
      single carrier requiring 1-month advance notice. Most carriers required some
      notification of oxygen needs by the traveler's physician. There was a great
      variation in oxygen device and liter flow availability. Liter flow options ranged
      from only two flow rates (36% of carriers) to a range of 1 to 15 L/min (one
      carrier). All carriers offered nasal cannula, which was the only device available
      for 21 carriers (84%). Actual charges for in-flight oxygen also varied greatly.
      Six carriers supplied oxygen free and 18 carriers charged a fee (range, $64 to
      $1,500). One airline allowed the traveler to bring one "E" cylinder with no fee
      assessed. For 14 of the 18 carriers that charged, the charge for the standard
      trip ranged from $100 to $250. CONCLUSIONS: (1) As expected from the lack of
      standard regulations, the availability, costs, and ease of implementing in-flight
      oxygen vary greatly among commercial air carriers. (2) Because the expense of in
      flight oxygen is usually borne by the traveler (rather than by insurers),
      prospective travelers should consider charges for oxygen use when choosing an
      airline. (3) In the context that the current study shows substantial variation in
      oxygen policies, costs, and services among commercial air carriers and that such
      policies may change over time, our findings encourage the prospective air
      traveler needing in-flight oxygen to "shop around."

PMID- 10208200
TI  - Accuracy of an infrared tympanic thermometer.
AB  - BACKGROUND: The use of infrared thermometry to measure temperatures in
      hospitalized patients is increasing. Although infrared thermometers have been
      proven to be accurate when they are used by well-trained personnel, no previous
      studies have examined their accuracy during routine hospital use. OBJECTIVE: To
      determine the accuracy and observer variability of temperatures measured with an
      infrared tympanic thermometer (TT). DESIGN: Prospective, observational study.
      SETTING: ICUs of a 300-bed teaching community hospital. PATIENTS: Fifty-one
      critically ill patients. MEASUREMENTS: The mean of three tympanic temperatures
      measured with the infrared TT (tempTTs) was compared to temperatures
      simultaneously measured with the thermistor of right heart catheters and rectal
      mercury thermometers for the following three groups of observers who had been
      certified in the use of the infrared TT: a single critical care nurse
      (CCN)/educator (Ed); CCNs, and floor nurses (FNs)/clinical care practitioners
      (CCPs). RESULTS: Two rounds of measurements were given to 51 patients by 153
      observers. Temperatures of the pulmonary artery (PA) measured with the thermistor
      of right heart catheters (tempPAs) ranged from 96.5 to 102.6 degrees F, with a
      mean (-/+ SD) of 99.3+/-1.1 degrees F. The intraobserver variabilities
      (correlation coefficients) of the tempTTs ranged from 0.90 for those measured by
      FNs/CCPs, to 0.92 for those measured by CCNs, to 0.98 for those measured by the
      CCN/Ed. Accuracy, arbitrarily defined as within a deviation of -/+0.5 degrees F
      of the tempPA, was 100% for the rectal mercury thermometer and 98.0% for the
      infrared TT when used by the CCN/Ed. The accuracy of the infrared TT was 80% when
      measured by CCNs and 61% when measured by FNs/CCPs. Differences between tempPAs
      and tempTTs measured by the CCN/Ed ranged from 0 to 0.7 degrees F, with a mean of
      0.2 degrees F. Similarly, differences between tempPAs and tempTTs measured by
      CCNs ranged from 0 to 2.4 degrees F, with a mean difference of 0.3 degrees F.
      However, differences between tempPAs and tempTTs measured by FNs/CCPs ranged from
      0 to 3.0 degrees F, with a mean of 0.6 degrees F (greater differences than those
      obtained by the CCNs; p < 0.01). The accuracy of rectal mercury thermometry was
      100%. If a temperature > or = 101.0 degrees F had been considered as the
      threshold at which a fever is present, and if the mean of three measurements had
      been used to designate temperature, workups that were either inappropriately
      performed or omitted would have resulted from 2% of tempTTs measured by the
      CCN/Ed, 1% of those measured by CCNs, and 4% of those measured by FNs/CCPs.
      CONCLUSION: When used properly, both tympanic and rectal thermometry are very
      accurate. However, the infrared TT produced measurements that were both less
      accurate and less reproducible when used by nurses who routinely used it in
      clinical practice.

PMID- 10208199
TI  - Immediate and long-term results of bronchial artery embolization for life
      threatening hemoptysis.
AB  - STUDY OBJECTIVES: Bronchial artery embolization (BAE) has been established as an
      effective technique in the emergency treatment of life-threatening hemoptysis,
      but few data concerning long-term results and complications of the procedure are
      available. The aim of this study was to analyze retrospectively the experience of
      BAE in our center with particular emphasis on medium-term and long-term results
      and on morbidity. SETTING: University hospital. PATIENTS: Fifty-six patients
      underwent bronchial arteriography from 1986 to 1996 in our center for the
      management of life-threatening hemoptysis. Of them, BAE was performed in 46
      patients. Their mean age was 51 years (range, 19 to 89 years). The most frequent
      etiologies of hemoptysis were active or inactive tuberculosis, bronchiectasis, or
      idiopathic hemoptysis. RESULTS: BAE resulted in an immediate cessation of
      hemoptysis in 43 of the initial 56 patients (77%). During the first month after
      BAE, four patients who died from causes other than hemoptysis or who were
      referred to surgery were excluded from follow-up and in the 39 remaining
      patients, a complete cessation of hemoptysis was observed in 32 patients. A
      remission was noted in 28 of the 29 patients followed up between 30 and 90 days
      after BAE. Long-term control of bleeding was achieved in 25 of the initial 56
      patients (45%) followed up beyond 3 months after BAE (median follow-up of 13
      months; range, 3 to 76 months). Overall, complications of BAE consisted of two
      episodes of mediastinal hematoma and three episodes of neurologic damage, two of
      which improved without permanent sequelae. CONCLUSION: We conclude that BAE may
      result in long-term as well as immediate control of life-threatening hemoptysis
      but that complications are not unusual.

PMID- 10208201
TI  - Pulmonary function improves after expandable metal stent placement for benign
      airway obstruction.
AB  - STUDY OBJECTIVE: To determine whether expandable metal stent placement for benign
      airway lesions improves pulmonary function. DESIGN: Case series. SETTING:
      University medical center. PATIENTS: Nine patients who underwent balloon-mediated
      expandable metal stent deployment for airway obstruction due to benign
      etiologies. RESULTS: All nine patients had expandable stents deployed for benign
      airway lesions using fiberoptic bronchoscopy and fluoroscopic guidance. Pulmonary
      function improved after stent placement. The mean FVC increased by 388 mL (95%
      confidence interval [CI], 30 to 740 mL), the mean peak expiratory flow (PEF)
      increased by 1,288 mL (95% CI, 730 to 1,840 mL), the mean FEV1 increased by 550
      mL (95% CI, 240 to 860 mL), and the mean forced expiratory flow between 25% and
      50% of vital capacity (FEF25-75%) increased by 600 mL (95% CI, 110 to 1,090 mL).
      Corresponding relative measurements included increases in FVC (12%), PEF (95%),
      FEV1 (38%), and FEF25-75% (87%). The complete characterization of a benign airway
      obstruction generally required a multimodal approach. CONCLUSIONS: Expandable
      metal stent placement appears to be an effective therapy for benign airway
      obstruction.

PMID- 10208202
TI  - FDG SPECT in patients with lung masses.
AB  - STUDY OBJECTIVES: To determine whether 2-[fluorine-18]fluoro-2-deoxy-D-glucose
      (FDG) single-photon emission CT (SPECT) is useful in characterizing pulmonary
      masses. DESIGN: Scans were prospectively acquired and interpreted.
      Interpretations were performed with CT or chest radiograph but interpreters were
      blinded to eventual diagnosis. SETTING: University hospital practice and
      affiliated Veterans Administration medical center. PATIENTS OR PARTICIPANTS:
      Forty patients participated as part of an institutional review board-approved
      research protocol, and informed consent was obtained in all. Eight additional
      patient scans were acquired as part of their clinical evaluation for pulmonary
      mass. MEASUREMENTS AND RESULTS: There were 26 malignant lesions (12 were 1 to 2
      cm in size, the rest were larger) and 17 benign lesions (3 were < 1 cm in size, 9
      were 1 to 2 cm in size, and 5 were larger). Averaged sensitivity, specificity,
      positive predictive value, and negative predictive value were, respectively, 50%
      (12 of 24), 94% (17 of 18), 92% (12 of 13), and 59% (17 of 29) for lesions 1 to 2
      cm in size, 100% (28 of 28), 90% (9 of 10), 97% (28 of 29), and 100% (9 of 9) for
      lesions > 2 cm in size. There was good correlation between readers (p < 0.0001).
      CONCLUSION: FDG SPECT is useful in characterizing pulmonary masses > 2 cm in size
      and appears to be equivalent to positron emission tomography for these lesions.
      Although currently clinically suboptimal for characterizing lesions < or = 2 cm
      in size, FDG SPECT appears to be better than current anatomic imaging methods. In
      addition, the positive predictive value of FDG SPECT for small lesions is also
      high (92%), and this technique appears potentially useful in the subset of
      patients in whom a positive result would alter clinical diagnostic pathways or
      care.

PMID- 10208203
TI  - Histopathologic prognostic factors in resected adenocarcinomas: is nuclear DNA
      content prognostic?
AB  - BACKGROUND: The pathobiological characteristics of lung adenocarcinoma are still
      unclear. To identify the factors that may affect the survival of patients
      undergoing pulmonary resections for adenocarcinoma of the lung, univariate and
      multivariate analyses were performed for 17 variables of the host,
      histopathology, nuclear DNA content (NDC), and morphometry of nucleus (nuclear
      area [NA]) of tumor cells. METHODS: Seventy-two consecutive patients who
      underwent resection at the National Cancer Center in Tokyo were studied. They
      consisted of 45 men and 27 women with an average age of 61.7 years (range, 27 to
      83 years). For these patients, NDC and NA were prospectively measured by
      cytofluorometry and morphometry, respectively. For univariate analysis, 17
      factors were studied, including age, sex, TNM stage, diameter of the tumor,
      pleural involvement, degree of differentiation, scar grade, nuclear atypia,
      mitotic index, histogram pattern of NDC, mean NDC, number of aneuploid stem cell
      lines, and mean and SD of NA. A multivariate analysis was performed with Cox's
      regression model for 16 variables. RESULTS: In the univariate analysis, 12
      factors were significantly related to postoperative survival, including TNM
      stage, diameter, pleural involvement, nuclear atypia, mitotic index, mean NA,
      mean NDC, number of aneuploid stem cell lines, and the DNA histogram pattern. In
      the multivariate analysis, M, T, and the histogram pattern of NDC were
      significantly associated with survival while N showed a strong, but not
      significant, association. CONCLUSIONS: Multivariate analysis of histopathologic
      prognostic factors indicated that the TNM stage, as well as each component
      independently, still provided the greatest prognostic value in resected
      adenocarcinomas of the lung. Among other factors, only NDC significantly affected
      survival. The importance of NDC measurement should be stressed for predicting the
      survival after surgical resection more accurately and for selecting patients with
      a higher risk of recurrence.

PMID- 10208204
TI  - Performance of an algorithm to detect Pneumocystis carinii pneumonia in
      symptomatic HIV-infected persons. Pulmonary Complications of HIV Infection Study
      Group.
AB  - STUDY OBJECTIVES: To determine whether an algorithm consisting of a chest
      radiograph and the diffusing capacity of the lung for carbon monoxide (D(LCO)) is
      effective in detecting Pneumocystis carinii pneumonia (PCP) in symptomatic HIV
      infected persons; and to establish a benchmark for future comparisons of
      alternative algorithms. DESIGN: Prospective, 64-month study. SETTING:
      Multicenter, ambulatory care. PATIENTS: 306 HIV-infected subjects enrolled in the
      Pulmonary Complications of HIV Infection Study who developed 467 episodes of new
      or worsening respiratory symptoms. MEASUREMENTS: Chest radiography followed by
      D(LCO) measurement, if the radiograph was normal or unchanged. RESULTS: An
      algorithm combining a chest radiograph followed by a D(LCO) measurement, if the
      radiograph was normal or unchanged, was effective and detected abnormalities that
      led to a diagnosis of PCP in 78 of 80 evaluable episodes (97.5%). The radiograph
      (specific parenchymal abnormality, number of lung zones involved) and the D(LCO)
      (degree of decrease, degree of decrease from baseline) also provided additional
      information on the probability of PCP. CONCLUSIONS: In symptomatic HIV-infected
      patients suspected of having PCP, the diagnostic evaluation should begin with a
      chest radiograph, followed by a D(LCO) measurement, if the radiograph is normal
      or unchanged. If both of these tests are normal, it may be reasonable to conclude
      the evaluation rather than to proceed on to additional testing. This algorithm
      can serve as a benchmark for future comparisons.

PMID- 10208205
TI  - Mycobacterium avium-intracellulare pulmonary infection in HIV-negative patients
      without preexisting lung disease: diagnostic and management limitations.
AB  - STUDY OBJECTIVES: To review the experience of an outpatient pulmonary clinic with
      Mycobacterium avium-intracellulare (MAI) pulmonary disease in the HIV-negative
      population without preexisting lung disease. DESIGN: Retrospective clinical
      series. SETTING: University medical center. PATIENTS: The clinic charts of all
      patients who fulfilled the current American Thoracic Society criteria for MAI
      pulmonary infection and who had no preexisting lung disease or immunosuppression
      were reviewed. MEASUREMENTS AND RESULTS: Of 31 patients identified, 94% were
      female, 90% were white, and the median age at diagnosis was 63 years. The median
      time interval from symptom onset to diagnosis was 10 months. Bronchiectasis or
      small nodules without predilection for any lobe was found in 93%. Bronchoscopy or
      open lung biopsy for diagnosis was required in 45% because of nondiagnostic
      sputum cultures. At > or = 12 months, 50% failed therapy, 86% continued to be
      symptomatic, and 58% did not tolerate their initial multidrug regimen.
      CONCLUSIONS: These results emphasize the observed chronic nature of MAI pulmonary
      disease in this population, both before diagnosis and despite therapy. The
      sensitivity of sputum culture in this population is low, so an aggressive
      diagnostic approach, including bronchoscopy, should be considered if sputum
      cultures are negative. Current treatments are suboptimal because of poor drug
      tolerance and significant failure rates. Last, the preponderance of disease in
      older white women argues for a genetic or acquired immune deficiency to explain
      disease susceptibility.

PMID- 10208206
TI  - Comprehensive evaluation of 35 patients with lymphangioleiomyomatosis.
AB  - OBJECTIVES: To evaluate comprehensively the characteristics of
      lymphangioleiomyomatosis (LAM), with emphasis on the application of imaging and
      immunohistochemical methods. DESIGN: Prospective study. PATIENTS: Thirty-five
      female subjects with LAM. SETTING: Clinical Center, National Institutes of
      Health. INTERVENTIONS: BAL, pulmonary function test, ventilation/perfusion lung
      scans, CT of the chest and abdomen, ultrasonography of abdomen, and
      immunohistochemical study of lung biopsy specimens. RESULTS: Most patients had
      exertional dyspnea (83%) and pneumothorax (69%). BAL did not show diagnostic
      changes. The most common abnormalities on pulmonary function tests were decreased
      diffusing capacity of carbon monoxide (83%), hypoxemia (57%), and airway
      obstruction (51%). Bronchodilator response was found in 26% of patients. CT,
      which is almost pathognomonic, showed numerous thin-walled cysts throughout both
      lungs in all patients. Thirty-four patients (97%) had abnormal ventilation and/or
      perfusion lung scans. An unusual "speckling" pattern was observed on ventilation
      scans of 74% of patients. Common extrapulmonary features were retroperitoneal
      adenopathy (77%) and renal angiomyolipomas (60%). The percentage of abnormal
      smooth muscle cells (LAM cells), reactive with HMB45, varied from 17 to 67% in 10
      lung biopsy specimens. CONCLUSIONS: Improved diagnostic methods have defined the
      abnormalities in patients with pulmonary LAM and increased the potential for
      early recognition and treatment of this disorder. Patients with LAM should be
      evaluated for bronchodilator responsiveness and may benefit from a trial of
      bronchodilators.

PMID- 10208207
TI  - The use of anti-inflammatory medications in cystic fibrosis: trends and physician
      attitudes.
AB  - STUDY OBJECTIVES: In recent years, there has been considerable interest in the
      use of antiinflammatory medications to decrease airway inflammation and preserve
      pulmonary function in patients with cystic fibrosis (CF) lung disease. Long-term
      use of oral corticosteroids (OCS) and ibuprofen (IBU) has been proven efficacious
      in slowing the progression of CF. Inhaled corticosteroids (ICS) have not been
      adequately studied. Little is known regarding use trends and physician attitudes
      toward these drugs. DESIGN: Cross-sectional survey mailed to 111 directors of
      Cystic Fibrosis Centers in the United States accredited by the Cystic Fibrosis
      Foundation. The two-page written questionnaire included items regarding
      physicians' attitudes toward anti-inflammatories, center demographics, patients
      receiving therapy, and number of physicians prescribing therapy. RESULTS: Sixty
      seven surveys were returned (60%). The responding centers represented 239
      physicians and served 9,363 patients, 2,234 (24%) of whom were receiving routine
      antiinflammatory drugs. Complete data sets were available for 8,803 patients with
      2,169 (25%) receiving anti-inflammatory therapy. Ninety-eight (41%) physicians
      prescribed long-term use of oral steroids for 413 (5%) patients, 103 (42%)
      prescribed inhaled steroids for 1,032 (12%) patients, and 108 (45%) prescribed
      high-dose IBU for 723 (8%) patients to control CF. The practitioners reported
      familiarity and efficacy as the primary reasons for prescribing OCS; concerns
      over side effects were the major reason for not prescribing. Regarding ICS, the
      primary reasons for prescribing were familiarity and safety, with lack of
      efficacy being cited as the major reason for not prescribing. For IBU, efficacy
      was ranked highest among reasons for prescribing, with concern over safety being
      the highest ranked reason for not prescribing. CONCLUSIONS: Anti-inflammatory
      medications appear to be an underutilized therapeutic modality in CF care. This
      is true for numbers of patients receiving these drugs as well as numbers of care
      providers prescribing them. Additional studies will be required to address
      physicians' concerns regarding the long-term efficacy and safety of anti
      inflammatory drugs in treating CF.

PMID- 10208208
TI  - Value of ICAM-1 expression and soluble ICAM-1 level as a marker of activity in
      sarcoidosis.
AB  - BACKGROUND: The natural course of sarcoidosis is variable, but no single
      parameter has been generally accepted as a good marker for disease activity.
      Adhesion molecules are required for the migration of inflammatory cells; thus,
      they may be markers of activity in sarcoidosis. METHODS: In 16 patients with
      active sarcoidosis and 11 with inactive disease (10 were male, 17 were female;
      mean age [-/+ SD], 39.6+/-11.0 years; mean follow-up, 21+/-16 months), the
      expression of adhesion molecules on cells obtained with BAL (measured by flow
      cytometry) and the level of soluble intercellular adhesion molecule 1 (sICAM-1)
      in the serum and BAL fluid (BALF) were measured at the time of diagnosis and
      during the follow-up. The changes in serum sICAM-1 level and ICAM-1 expression on
      cells obtained with BAL were compared with the clinical course of the disease.
      RESULTS: In patients with active disease, the ICAM-1 on alveolar macrophage (AM)
      (relative linear median fluorescence intensity [RMFI], 3.21+/-1.55) and sICAM-1
      levels in serum (575+/-221 ng/mL) and BALF (47.3+/-19.3 ng/mL) were higher than
      those for patients with inactive disease (RMFI, 1.67+/-0.66; p = 0.0034; serum,
      263+/-98.5 ng/mL; p = 0.0001; BALF, 27.5+/-19.0 ng/mL; p = 0.0209). In the
      patients with active disease, ICAMN-1 on AM and serum sICAM-1 decreased (RMFI,
      1.51+/-0.84; 284+/-118 ng/mL, respectively) after steroid therapy, but no
      significant change was noted in patients with inactive disease. We also found
      that the initial ICAM-1 on AM and serum sICAM-1 had a significant correlation
      with the degree of improvement in pulmonary function tests after the therapy. The
      disease relapsed in four patients after the discontinuation of steroids, and the
      serum sICAM-1 level was elevated again at the time of relapse. CONCLUSION: Our
      data suggest that the serum sICAM-1 level and the ICAM-1 expression on AM may be
      good markers of disease activity and also a predictor of outcome in sarcoidosis.

PMID- 10208209
TI  - Hypoalbuminemia as a cause of pleural effusions.
AB  - BACKGROUND: Alterations in Starling forces that favor pleural fluid formation
      include an elevation in capillary hydrostatic pressure and a fall in plasma
      oncotic pressure. Although venous hypertension is a well-recognized cause of
      pleural effusion, the frequency with which hypoalbuminemia in the absence of
      volume expansion leads to pleural effusion is unclear. STUDY OBJECTIVE: We
      determined the frequency with which unexplained pleural effusions occur in
      patients with normal and low plasma oncotic pressures. DESIGN: A 2-month
      prospective screen of all admission patients to the University of Oklahoma
      Hospital and the Oklahoma City Veterans Administration (VA) Medical Center
      identified 152 patients who had chest radiographs and serum protein
      determinations on admission, but did not have an admission diagnosis that was a
      recognized cause of pleural effusion. In order to include more patients in the
      study with extremely low serum albumin levels, 20 additional study patients with
      serum albumin levels of < 2.0 g/dL were identified by a retrospective review of
      patients admitted during the previous 12 months. On the radiograph, pleural
      effusions were identified as a new blunting of the costophrenic angles. Study
      patients were divided into the following three groups: group 1 had serum albumin
      levels of > 3.5 g/dL; group 2 had serum albumin levels between 2.1 and 3.5 g/dL;
      and group 3 had serum albumin levels of < or = 2.0 g/dL. Finally, the frequencies
      with which pleural effusions occurred were compared among the three groups.
      RESULTS: Seven of 104 patients in group 1, 2 of 45 patients in group 2, and 3 of
      21 patients in group 3 had pleural effusions. Within each group, there were no
      significant differences in serum albumin concentration or plasma oncotic pressure
      between patients with and without pleural effusions. In all but two study
      patients, a careful review of records and a prospective follow-up of the
      patients' clinical course identified a potential cause for the effusions other
      than hypoalbuminemia. None of the 68 study patients with serum albumin levels of
      < or = 3.5 g/dL had an unexplained pleural effusion. CONCLUSION: We conclude that
      hypoalbuminemia, per se, is an uncommon cause of pleural effusion. The
      recognition of pleural effusions in patients with low serum albumin levels should
      prompt careful clinical evaluations to identify other potential causes for the
      effusions.

PMID- 10208210
TI  - Late outcome from percutaneous tracheostomy using the Portex kit.
AB  - OBJECTIVE: To assess late outcome following percutaneous tracheostomy using the
      Portex kit (Hythe, Kent, UK). DESIGN: Prospective observational cohort study.
      SETTING: Teaching hospital. PATIENTS: Forty-nine consecutive patients who
      underwent percutaneous tracheostomy in the ICU using the Portex kit and who
      survived 6 months after the procedure. INTERVENTIONS: Questionnaires regarding
      six symptoms were sent to all 49 surviving patients; the 39 respondents were
      invited to attend for review. Thirteen patients underwent pulmonary function
      testing, of whom 10 also underwent fiberoptic laryngotracheoscopy under local
      anesthesia. RESULTS: The most common symptom was a minor change in voice. One
      patient had required treatment for symptomatic tracheal stenosis by the time of
      review; one was referred for revision of a tethered scar. Pulmonary function
      testing was easily performed by all patients and revealed no evidence of upper
      airway obstruction. Tracheoscopy likewise showed no evidence of tracheal
      stenosis. CONCLUSIONS: One of 49 patients had developed tracheal stenosis. None
      of the patients attending for detailed review showed any sign of late
      complications other than one tethered scar.

PMID- 10208211
TI  - The clinical utility of invasive diagnostic techniques in the setting of
      ventilator-associated pneumonia. Canadian Critical Care Trials Group.
AB  - OBJECTIVE: To evaluate the clinical utility of bronchoscopy with protected brush
      catheter (PBC) and BAL for patients with ventilator-associated pneumonia (VAP).
      DESIGN: Prospective cohort study. SETTING: Ten tertiary care ICUs in Canada.
      PATIENTS: Ninety-two mechanically ventilated patients with a clinical suspicion
      of VAP who underwent bronchoscopy were compared with 49 patients with a clinical
      suspicion of pneumonia who did not. INTERVENTIONS: None. MEASUREMENTS AND
      RESULTS: We compared antibiotic use, duration of mechanical ventilation, ICU
      stay, and mortality. In addition, for patients who received bronchoscopy, we
      administered a questionnaire (before and after bronchoscopy) to evaluate the
      effect of PBC or BAL on (1) physician perception of the probability of VAP, (2)
      physician confidence in the diagnosis of VAP, and (3) changes to antibiotic
      management. After bronchoscopy results became available, from the physician's
      perspective, the diagnosis of VAP was deemed much less likely (p < 0.001),
      confidence in the diagnosis increased (p = 0.03), and level of comfort with the
      management plan increased (p = 0.02). Following the results of invasive
      diagnostic tests, in the group that underwent bronchoscopy, patients were
      receiving fewer antibiotics (31/92 vs 9/49, p = 0.05) and more patients had
      treatment with all their antibiotics discontinued (18/92 vs 3/49, p = 0.04)
      compared with the group that did not undergo bronchoscopy. Duration of mechanical
      ventilation and ICU stay were similar between the two groups, but mortality was
      lower in the group that underwent bronchoscopy with PBC or BAL (18.5% vs 34.7%, p
      = 0.03). CONCLUSIONS: Invasive diagnostic testing may increase physician
      confidence in the diagnosis and management of VAP and allows for greater ability
      to limit or discontinue antibiotic treatment. Whether performing PBC or BAL
      affects clinically important outcomes requires further study.

PMID- 10208212
TI  - The incidence of and clinical variables associated with vancomycin-resistant
      enterococcal colonization in mechanically ventilated patients.
AB  - STUDY OBJECTIVES: (1) To determine in our ICU the incidence of vancomycin
      resistant enterococcus (VRE) colonization in mechanically ventilated patients
      without a history of VRE infection or colonization; and (2) to determine the risk
      factors and outcome variables associated with VRE colonization in these patients.
      DESIGN: A prospective cohort study conducted between January 1996 and March 1998.
      SETTING: Medical and cardiac critical care units in a tertiary care urban
      university hospital. PATIENTS: Mechanically ventilated patients without evidence
      of pneumonia at the onset of ventilation. INTERVENTIONS: None. MEASUREMENTS AND
      RESULTS: Patients underwent rectal cultures by standard methods on day 1, day 3
      or 4, day 6 or 7, and day 14 of intubation to detect VRE. Thirteen of 83 patients
      (16%) had rectal cultures positive for VRE (VRE+) at some point while being
      mechanically ventilated during their stay in the ICU. In comparison,
      approximately 15 of 2,100 medical ICU patients (0.7%) had clinical VRE infections
      as determined by the hospital's infection control program during a 2-year period.
      VRE+ patients had a higher incidence of immunosuppression than patients who had
      rectal cultures negative for VRE (VRE-) (9 of 13 [69%] vs 16 of 70 [23%],
      respectively; p < 0.01) and neutropenia (4 of 13 [31%] vs 5 of 70 [7%],
      respectively; p < 0.01). Hospital length of stay (LOS) was longer in VRE+
      patients than in VRE- patients (27+/-17 days vs 17+/-14 days, respectively; p =
      0.05), whereas pre-ICU hospital LOS and ICU LOS were similar in both patient
      groups. Five of 67 patients (7%) were VRE+ on day 1 of intubation, suggesting
      colonization at a prior site of care. Three of 29 patients who had subsequent
      rectal cultures converted to VRE+ while in the ICU. This group had a higher
      incidence of immunosuppression and neutropenia, and received more vancomycin
      compared with the patients who remained VRE- (p < 0.01). However, there was no
      significant difference in the use of other broad-spectrum antibiotics (such as
      antipseudomonal penicillins, third-generation cephalosporins, quinolones, and
      clindamycin), enteral tube feedings, or sucralfate between the two groups. In
      addition, a topical antibiotic paste (a gentamicin, nystatin, polymixin slurry)
      that was placed in the oropharynx to prevent bacterial overgrowth was not found
      to increase the incidence of VRE colonization in this patient population.
      CONCLUSIONS: The incidence of VRE colonization was surprisingly high: 16% in
      mechanically ventilated patients in a hospital in which VRE was not previously
      known to be endemic. Risk factors for the acquisition of VRE colonization
      included immunosuppression, neutropenia, and vancomycin use. Increased LOSs and
      hospital costs were seen in VRE+ patients compared to VRE- patients. Whether VRE
      colonization is a contributor to severe disease that leads to prolonged
      hospitalization and increased resource allocation or whether it is simply a
      marker of disease severity cannot be determined from this study. To the extent
      that specific antibiotic protocols are used to reduce antibiotic-resistant flora
      in the ICU, monitoring the incidence of VRE in the stool specimens of
      immunocompromised, mechanically ventilated patients can be a simple and useful
      tool to assess one effect of these strategies.

PMID- 10208213
TI  - Significant tracheal obstruction causing failure to wean in patients requiring
      prolonged mechanical ventilation: a forgotten complication of long-term
      mechanical ventilation.
AB  - INTRODUCTION: Modern low-pressure, high-volume cuffed tracheotomy tubes have been
      shown to decrease tracheal injury. However, injury still occurs in patients
      requiring prolonged mechanical ventilation and prevents weaning, delays
      decannulation, prolongs hospitalization, and may totally obstruct the airway. We
      describe 37 patients, including the first reported case of failure to wean due to
      tracheal obstruction. METHODS: Over a 3-year period, from September 1994 to
      August 1997, the hospital records of 37 patients requiring prolonged mechanical
      ventilation (> 4 weeks) and found to have tracheal obstruction were reviewed
      retrospectively. They were a subgroup of 756 patients admitted to hospitals
      during the same period. The average endotracheal/tracheostomy cannulation time
      was 3 weeks/12 weeks (range 2 to 4 weeks/8 to 14 weeks). Average age was 76 years
      (range, 34 to 81). Underlying diseases included COPD, postcoronary artery bypass
      graft surgery, postpneumonectomy, severe pneumonia, acute lung injury, and
      ischemic heart disease. RESULTS: All 37 patients who initially failed to wean had
      difficulty in breathing and developed intermittent high peak airway pressures
      either early or during the weaning process or just on being ventilated. The
      insertion of a longer tracheal tube bypassed the obstruction, reestablished the
      airway, decreased peak airway pressures, and allowed the patient to breathe more
      easily. The obstruction was confirmed on bronchoscopy. Treatment consisted of
      either placement of a longer tracheal tube (34 of 37 patients) or placement of a
      tracheal stent. All but two of the patients (5.4%) were able to be weaned within
      a week. The two patients who still failed to be weaned were subsequently
      diagnosed as having amyotrophic lateral sclerosis. CONCLUSION: Tracheal
      obstruction in patients requiring prolonged mechanical ventilation prevented
      weaning. Reestablishment of the airway with a longer tracheal tube or tracheal
      stent allowed most of the patients to be weaned.

PMID- 10208214
TI  - The unidirectional valve is the best method to determine maximal inspiratory
      pressure during weaning.
AB  - OBJECTIVES: Although maximal inspiratory pressure (MIP) is used as an index of
      inspiratory muscular strength, there is no consensus on how to measure it. We
      compared, during weaning from mechanical ventilation, two methods of measurement
      to determine which shows the greater values (MIPbest) and is more reproducible.
      One method measured MIP when negative pressure was maintained for at least 1 s
      after a forceful expiration, and the other method measured MIP with a
      unidirectional expiratory valve (MIPuni). DESIGN: The study had a crossover
      design, and patients randomly performed three measurements of each method (t1).
      The procedure was repeated by the same observer after 20 min (t2). The maximal
      value in each method was considered. SETTING: ICU, Hospital A.C. Camargo, Sao
      Paulo, Brazil. PATIENTS: Fifty-four consecutive patients undergoing short-term
      mechanical ventilation who became eligible for the study when their physicians
      decided to restore spontaneous breathing. RESULTS: MIPbest values were arrived at
      using MIPuni 75% of the time either in tl or t2. MIPuni yielded a higher average
      of MIPbest values in t1 and t2 (p < 0.0001). The effort-to-effort coefficient of
      variation of one method compared with the other during t1 and t2 was similar (p >
      0.2 for t1; p > 0.8 for t2). Also, when comparing tl and t2, the coefficients of
      variation were similar for each method (p > 0.62). CONCLUSIONS: Because MIPuni
      displayed the maximal values, it is the best method for estimating MIP in
      patients undergoing short-term mechanical ventilation. The reproducibility of
      consecutive measurements was similar between the methods, even after a short
      period of time.

PMID- 10208215
TI  - Evaluation of electrical impedance tomography in the measurement of PEEP-induced
      changes in lung volume.
AB  - STUDY OBJECTIVES: A new noninvasive practical technique called electrical
      impedance tomography (EIT) was examined for the measurement of alveolar
      recruitment. DESIGN: Prospective clinical study. SETTING: ICU of a general
      hospital. PATIENTS: Acute respiratory failure (ARF) patients. MEASUREMENTS: The
      ventilation-induced impedance changes (VICs) of the nondependent and the
      dependent part of the lung were determined by EIT as a measure of tidal volume
      distribution. By the use of an impedance ratio (IR), defined as the VIC of the
      nondependent part of the lung divided by the VIC of the dependent part of the
      lung, the ventilation performances in both parts of the lung were compared to
      each other. RESULTS: Between patients, the VIC of the nondependent part of the
      lung was significantly lower in the patients with a level of positive end
      expiratory pressure (PEEP) of > 10 cm H2O than in patients with a PEEP of < 5 cm
      H2O (p < 0.05). A significantly lower IR (-/+ SD) was found in the group with
      PEEP of > 10 cm H2O than in the group with PEEP between 0 and 5 cm H2O (1.28+/
      0.58 vs 2.99+/-1.24, respectively; p < 0.01). In individual patients, the VIC of
      the whole lung increased when the PEEP level was increased. The VICs of the
      nondependent part of the lung and of the dependent part of the lung showed
      significant increases at a PEEP of 10 cm H2O compared to a PEEP of 0 cm H2O (p <
      0.05). Also the IR decreased in individual patients when the PEEP was increased;
      a significant decrease was found at 10 cm H2O compared to 0 cm H2O (1.67+/-1.24
      vs 2.23+/-1.47, respectively; p < 0.05). CONCLUSIONS: The decrease in IR
      indicates an increase in VIC in the dependent part of the lung above the
      nondependent part of the lung. The increase in VIC can be regarded as an increase
      in lung volume, implying alveolar recruitment in the dependent part of the lung.
      The same results also have been shown in earlier reports by CT scan. Since EIT is
      far more practical than CT scanning and also is a bedside method, EIT might help
      in the adjustment of ventilator settings in ARF patients.

PMID- 10208216
TI  - The potential for dissemination of Mycobacterium tuberculosis through the
      anesthesia breathing circuit.
AB  - BACKGROUND: Respiratory pathogens that pass through the anesthesia breathing
      system potentially can infect other patients. This study was designed to
      determine if bacteria can pass through contemporary anesthesia breathing systems
      and if the environment within the machine is hostile to these organisms. METHODS:
      Staphylococcus aureus, Pseudomonas aeruginosa, and Mycobacterium tuberculosis
      were nebulized into the expiratory limb of an anesthesia breathing circuit and
      collected from the inspiratory and expiratory limbs in an impinger system that
      provided a quantitative determination of the number of organisms entering the
      circuit and the number that would reach the patient in the inspiratory gas.
      Bacteria were collected before, during, and after nebulization. A second
      experiment determined if a saturated solution of soda lime was bactericidal.
      RESULTS: When the gas flow through the circuit was interrupted for < 1 h
      following the nebulization period, large numbers of microorganisms (1 x 10(3) to
      1 x 10(5), around 100% of the nebulized organisms) were collected from the
      inspiratory gas. Soda lime itself was not bactericidal for any of the organisms
      tested, but solutions of this material with a pH of 12 were bactericidal.
      CONCLUSION: Cross contamination between patients may occur unless the gas flow
      through the anesthesia breathing system is interrupted for > 1 h.

PMID- 10208217
TI  - Argyrophilic nucleolar organizer regions in cells of thymoma and thymic
      carcinoma: correlation with DNA ploidy and clinicopathologic characteristics.
AB  - STUDY OBJECTIVES: To evaluate the usefulness of argyrophilic nucleolar organizer
      region (AgNOR) counting and flow cytometric DNA analysis in the differential
      diagnosis of thymoma and thymic carcinoma, as well as in the differences among
      various stages and histologic subtypes of these tumors. DESIGN AND INTERVENTIONS:
      Paraffin-embedded blocks of 64 thymic epithelial tumors (20 noninvasive thymomas,
      34 invasive thymomas, and 10 thymic carcinomas) were studied by AgNOR counting
      and flow cytometric DNA analysis. The thymomas were histologically classified as
      medullary, cortical, or mixed subtype. MEASUREMENTS AND RESULTS: Invasive
      thymomas had more AgNORs (-/+ SD) than noninvasive thymomas (7.93+/-2.90 vs
      5.97+/-1.77; p < 0.01). The number of AgNORs of thymoma increased progressively
      with advances in stage (p < 0.01). Cortical thymomas had the highest number of
      AgNORs among the three subtypes (p < 0.05). Patients with thymoma who presented
      with myasthenia gravis also had a higher number of AgNORs (8.30+/-3.12 vs 6.50+/
      2.03; p < 0.01). The AgNOR number did not correlate with the DNA ploidy of all
      specimens. CONCLUSIONS: AgNOR counting is useful in differentiating between
      invasive and noninvasive thymomas, and in predicting the stage of thymomas. A
      greater number of AgNORs was observed in patients with cortical thymoma and in
      those who presented with myasthenia gravis.

PMID- 10208218
TI  - Emerging therapies for cystic fibrosis lung disease.

PMID- 10208219
TI  - The upper airway resistance syndrome.
AB  - The upper airway resistance syndrome (UARS) is a recently described form of sleep
      disordered breathing in which repetitive increases in resistance to airflow
      within the upper airway lead to brief arousals and daytime somnolence. This
      review will first describe the chronological progression of our understanding of
      UARS within the broader context of sleep-disordered breathing. The primary
      symptom, daytime somnolence, appears to result directly from repetitive EEG
      arousals. The level of negative intrathoracic pressure is the most likely
      stimulus for arousal, possibly mediated by mechanoreceptors in the upper airway.
      A general consensus regarding the exact clinical definitions and the physiologic
      measurement techniques leading to a diagnosis does not exist, although esophageal
      manometry and pneumotachographic airflow measurements taken during
      polysomnography are the "gold standard." Less invasive diagnostic modalities have
      been proposed, but none of them have been well-validated. Aside from daytime
      somnolence, hypertension is an important sequela of this disorder, likely
      resulting from autonomic and cardiovascular changes induced by increased negative
      intrathoracic pressure. Nasal continuous positive airway pressure is the most
      efficacious form of therapy, although low patient compliance may limit its
      practical application. The safety and efficacy of surgical treatments are poorly
      documented in the literature. Palatal tissue reduction by radiofrequency ablation
      and the use of oral appliances hold promise as safe and effective modalities, but
      these treatments require further study.

PMID- 10208220
TI  - The laboratory-clinical interface: point-of-care testing.
AB  - POC testing provides an opportunity for clinicians and laboratorians to work
      together to consider how best to serve the patients within an individual
      institution. Each health system has unique characteristics relative to patient
      population, as well as a unique laboratory structure. If physicians, nurses,
      laboratorians, and pathologists work collaboratively, the best interests of
      patients will be served. In some institutions that cater to specific patient
      groups, POC testing may offer clear and distinct advantages. In other
      institutions with sophisticated transport systems and established rapid response
      capabilities, the quality resulting from central laboratory testing may outweigh
      any advantages of bedside testing. Clearly, attention to regulatory issues, QC
      issues, the importance of proper documentation, proficiency testing, performance
      enhancement, and cost-effectiveness is requisite. As the technology for
      diagnostic testing advances through more microcomputerization, microchemistry,
      and enhanced test menus, the concept of POC testing will need perpetual
      revisiting. We hope that the information provided here will aid clinicians,
      laboratorians, and administrators in their quest to best serve their patients.

PMID- 10208221
TI  - Presidential address--CHEST 1998.

PMID- 10208222
TI  - An approach to the treatment of pulmonary sarcoidosis with corticosteroids: the
      six phases of treatment.
AB  - Corticosteroid therapy for pulmonary sarcoidosis is not standardized. There is no
      consensus on which patients should receive treatment, how patients should be
      monitored, and the dose of corticosteroids once the decision to treat has been
      made. These issues are important for several reasons. First, inappropriate use of
      corticosteroids may result in unnecessary toxic reactions. Second, inadequate use
      of corticosteroids might result in permanent pulmonary and extrapulmonary organ
      dysfunction from sarcoidosis. Third, patients who are inappropriately labeled as
      "corticosteroid failures" may be subjected to other potentially toxic drugs or
      even lung transplantation. Corticosteroid dosing involves six phases: (1) initial
      high doses to control inflammation; (2) tapering to a maintenance dose that will
      continue to suppress the inflammation but lessen the risk of corticosteroid toxic
      reactions; (3) continuing to receive the maintenance dose until a decision to
      taper off corticosteroids is made; (4) tapering off corticosteroid therapy; (5)
      observation for relapse; and (6) treatment if relapse occurs. Although these
      phases of treatment have been alluded to in the literature, few of them have been
      studied rigorously. This article describes the use of corticosteroids for
      pulmonary sarcoidosis in terms of the above six phases. The proposed dosing
      schedules are based on the natural history of the disease and the results from
      published treatment studies.

PMID- 10208223
TI  - The treadmill test--where to stop and what does it mean?
AB  - The prognostic utility of an exercise ECG test depends upon having an adequate
      workload to stress the cardiac system. A negative stress test, in which there are
      no adverse clinical or ECG findings, and in which an adequate workload is
      achieved, stratifies patients into a low-risk group. The 1997 American Heart
      Association guidelines imply that any index of workload--heart rate, rate
      pressure product, or exercise duration in multiples of resting O2 consumption
      (METS)--could be used to indicate that adequate stress was achieved. However,
      while there is considerable evidence supporting the use of METS as a strong
      independent prognostic variable, there is less support for the use of rate
      pressure product or heart rate. Indeed, there is evidence that a high heart rate
      at a low workload carries an adverse prognosis. Further research is needed to
      identify the number of METS achieved that would define an adequate workload. In
      the meantime, a review of the literature suggests that 7 to 10 METS is a
      reasonable ballpark figure of the minimum workload in patients with a negative
      stress test that would imply a favorable outcome.

PMID- 10208224
TI  - Tumor necrosis factor-alpha: a mediator of disease progression in the failing
      human heart.

PMID- 10208225
TI  - Effect of betaxolol on the hemodynamic, gas exchange, and cardiac output response
      to exercise in chronic atrial fibrillation.
AB  - BACKGROUND: beta-blockade controls the ventricular response to exercise in
      chronic atrial fibrillation (AF), but the effects of beta-blockers on exercise
      capacity in AF have been debated. METHODS: Twelve men with AF (65+/-8 years)
      participated in a randomized, double-blind, placebo-controlled study of betaxolol
      (20 mg daily). Patients underwent maximal exercise testing with ventilatory gas
      exchange analysis, and a separate, submaximal test (50% of maximum) during which
      cardiac output was measured by a CO2 rebreathing technique. RESULTS: After
      betaxolol therapy, heart rate was reduced both at rest (92+/-27 vs 62+/-12
      beats/min; p < 0.001) and at peak exercise (173+/-22 vs 116+/-24 beats/min; p <
      0.001). Maximal oxygen uptake (VO2) was reduced by 19% after betaxolol (21.8+/
      5.3 with placebo vs 17.6+/-5.1 mL/kg/min with betaxolol; p < 0.05), with similar
      reductions observed for maximal exercise time, minute ventilation, and CO2
      production. VO2 was reduced by a similar extent (19%) at the ventilatory
      threshold. Submaximal cardiac output was reduced by 15% during betaxolol therapy
      (12.9+/-2.3 vs 10.9+/-1.3 L/min; p < 0.05), and stroke volume was higher (88.0+/
      21 vs 105.6+/-19 mL/beat; p < 0.05). CONCLUSION: Betaxolol therapy in patients
      with AF effectively controlled the ventricular rate at rest and during exercise,
      but also caused considerable reductions in maximal VO2 and cardiac output during
      exercise. The observed increase in stroke volume could not adequately compensate
      for reduced heart rate to maintain VO2 during exercise.

PMID- 10208226
TI  - Fevers, weight loss, and bilateral peripheral infiltrates in a young man.

PMID- 10208227
TI  - Multiple cavitating nodules in a patient with hemoptysis.

PMID- 10208229
TI  - Negative pressure pulmonary hemorrhage.
AB  - Negative pressure pulmonary edema, a well-recognized phenomenon, is the formation
      of pulmonary edema following an acute upper airway obstruction (UAO). To our
      knowledge, diffuse alveolar hemorrhage has not been reported previously as a
      complication of an UAO. We describe a case of negative pressure pulmonary
      hemorrhage, and we propose that its etiology is stress failure, the mechanical
      disruption of the alveolar-capillary membrane.

PMID- 10208228
TI  - Mycoplasma pneumoniae-associated bronchiolitis causing severe restrictive lung
      disease in adults: report of three cases and literature review.
AB  - STUDY OBJECTIVES: To characterize adult Mycoplasma pneumoniae-induced
      bronchiolitis requiring hospitalization. DESIGN: We encountered an adult patient
      with severe bronchiolitis in the absence of pneumonia due to M. pneumoniae. To
      determine the relative frequency of such a condition, we retrospectively reviewed
      the medical records of adults over a 4-year period with a hospital discharge
      diagnosis of "bronchiolitis" from a university hospital. SETTING: University
      Hospital of the University of Colorado Health Sciences Center, Denver, CO. STUDY
      SUBJECTS: From 1994 to 1998, 10 adult inpatients were identified with a diagnosis
      of bronchiolitis. There were two with respiratory bronchiolitis, one with
      panbronchiolitis, one patient with bronchiolitis obliterans organizing pneumonia
      (BOOP), and six with acute inflammatory bronchiolitis. Including the initial
      patient, three had a definitive clinical diagnosis of Mycoplasma-associated
      bronchiolitis. RESULTS: The three adult patients with bronchiolitis due to M.
      pneumoniae are unusual because they occurred in the absence of radiographic
      features of a lobar or patchy alveolar pneumonia. Hospital admission was
      occasioned by the severity of symptoms and gas exchange abnormalities. One
      patient had bronchiolitis as well as organizing pneumonia (BOOP) that responded
      favorably to corticosteroid treatment. The other two had high-resolution CT
      findings diagnostic of an acute inflammatory bronchiolitis. One of the patients
      with inflammatory bronchiolitis had an unusual pattern of marked ventilation and
      perfusion defects localized predominantly to the left lung. All three had
      restrictive ventilatory impairment on physiologic testing. CONCLUSIONS: In
      adults, Mycoplasma-associated bronchiolitis without pneumonia is rarely reported,
      but in hospitalized patients, it may be more common than expected and may be
      associated with severe physiologic disturbances.

PMID- 10208230
TI  - Propofol-induced pancreatitis: recurrence of pancreatitis after rechallenge.
AB  - We report a case of pancreatitis, which occurred while the patient was on a
      propofol drip and then recurred after resolution following an inadvertent
      rechallenge with propofol. The initial episode was associated with
      hypertriglyceridemia, whereas the latter was not. The association between
      propofol and pancreatitis is definite and may occur independently of significant
      hypertriglyceridemia.

PMID- 10208231
TI  - Recurrent pulmonary embolism associated with Klippel-Trenaunay-Weber syndrome.
AB  - Klippel-Trenaunay-Weber syndrome (KTWS) is a rare, congenital disorder
      characterized by the triad of varicose veins, cutaneous hemangiomas, and
      hypertrophy of soft tissue and bone. We present the case of a woman with KTWS,
      cor pulmonale, and death due to recurrent pulmonary embolism (PE). The risk of
      deep venous thrombosis and PE in patients with KTWS is evaluated, and treatment
      recommendations are made with emphasis on the role of early, aggressive
      management in the subset of patients with KTWS known to have thromboembolic
      disease.

PMID- 10208232
TI  - Heart transplantation after successful donor postpartum pulmonary embolectomy.
AB  - A fulminant pulmonary embolism can be treated surgically if thrombolytic therapy
      is contraindicated. A 31-year-old woman developed a fulminant pulmonary embolism
      after right-sided deep venous thrombosis 1 day after undergoing a cesarean
      section. A pulmonary embolectomy with cardiopulmonary bypass was performed, but
      the patient was brain-dead. After 2 days of echocardiographic observation, her
      heart was explanted for a 61-year-old man with ischemic cardiomyopathy. His right
      heart data were unremarkable, and he remains well 16 months after
      transplantation. Despite the sudden strain on the right ventricle that occurs
      with a pulmonary embolism, such a heart may be transplanted successfully after a
      pulmonary embolectomy.

PMID- 10208233
TI  - Severe intrapulmonary shunting associated with metastatic carcinoid.
AB  - A 37-year-old woman with a 10-year history of metastatic carcinoid presented to
      her oncologist with increased dyspnea. Further evaluation revealed hypoxemia and
      intrapulmonary vasodilatation. We describe a case of hepatopulmonary-like
      physiology associated with metastatic carcinoid in a patient with intact liver
      function. To our knowledge, this is the first documented case of intrapulmonary
      shunting and hepatopulmonary-like physiology associated with metastatic
      carcinoid.

PMID- 10208234
TI  - Pulmonary intravascular lymphomatosis: presentation with dyspnea and air
      trapping.
AB  - Intravascular lymphomatosis (IVL) is a rare lymphoid neoplasm that is typically
      of B-cell lineage and characterized by proliferation of malignant cells within
      small arterioles, capillaries, and venules. We report a patient with pulmonary
      IVL who presented clinically with progressive dyspnea, fever, and a dry cough.
      Pulmonary function tests revealed a marked decrease in diffusion capacity with
      airflow obstruction and severe air trapping. High-resolution CT (HRCT) of the
      chest with inspiratory and expiratory images revealed mosaic attenuation
      consistent with air trapping. Transbronchial biopsies revealed the diagnosis of
      IVL with capillary expansion in the alveolar and peribronchiolar interstitial
      tissue. IVL should be considered in the differential diagnosis of a patient with
      an interstitial lung disease, air trapping on pulmonary function tests, and
      mosaic attenuation on HRCT. Transbronchial biopsies may be the initial diagnostic
      procedure of choice.

PMID- 10208235
TI  - Extraction of a rubber bullet from a bronchus after 1 year: complete resolution
      of chronic pulmonary damage.
AB  - Inhalation of a foreign body (FB) into the bronchial tree rarely occurs
      asymptomatically and, if leading to recurrent pneumonia, can be very difficult to
      diagnose. The present report deals with the case of a 10-year-old boy who had
      three episodes of pneumonia in the left lower lobe caused by the asymptomatic
      inhalation of a FB 12 months before. Standard thoracic CT, done during the third
      episode, revealed a slight reduction in the volume of the left lung with air
      bronchograms, multiple areas of bronchiectasis, and parenchymal consolidation of
      a segment of the lower lobe. Flexible fiberoptic bronchoscopy revealed a FB at
      the distal end of the left lower lobar bronchus, surrounded by granulation tissue
      and fully obstructing the anterior basal segmental bronchus. High-resolution CT
      (HRCT) images showed an inverted C-shaped image obstructing a bronchus. Removal
      of the FB was successful only with rigid bronchoscopy under total anesthesia. The
      FB was an air-pistol rubber bullet that the boy remembered playing with 12 months
      before. Two months after removal of the FB (ie, 14 months from its asymptomatic
      inhalation) and treatment with oral steroids, antibiotics, and respiratory
      physiotherapy, the patient recovered completely, and HRCT showed complete
      normalization of the lung. We conclude that, when the radiographic density of the
      FB is greater than the surrounding pulmonary parenchyma, HRCT can reveal the FB,
      and diagnostic flexible fiberoptic bronchoscopy can be avoided.

PMID- 10208236
TI  - Temporary pacing after pneumonectomy.

PMID- 10208237
TI  - Choosing the appropriate control.

PMID- 10208238
TI  - Issues in ventilator weaning.

PMID- 10208239
TI  - Liberation from mechanical ventilation: now for the rest of the story.

PMID- 10208241
TI  - Audibility of fourth heart sound.

PMID- 10208242
TI  - Thoracic empyema in HIV-infected patients.

PMID- 10208243
TI  - Continuous i.v. sedation and mechanical ventilation.

PMID- 10208244
TI  - The use of inhaled nitric oxide during gas embolism.

PMID- 10208245
TI  - Strength training for 1h in humans: effect on the motor performance of normal
      upper extremities.
AB  - It has been found that one session of intense muscle strength training decreases
      muscle strength temporarily and causes neuromuscular fatigue in the trained
      muscles, but little attention has been given to the effects of neuromuscular
      fatigue on the other components of motor performance. The purpose of this study
      was to examine in normal healthy volunteers the effects of a 1-h strength
      training session on the motor performance of the upper extremity, including
      reaction time, speed of movement, tapping speed and coordination. Group of 30
      healthy female volunteers, aged 29-47 years, were randomly divided into sub
      groups, (A and B, n = 15 per group). Both groups first completed a set of motor
      performance tests on 3 consecutive days. On the 4th day, group A carried out a 1
      h muscle strength training session of the upper extremities. Isometric muscle
      strengths and electromyogram (EMG) data were recorded before the training
      session. Immediately after the training session the same recordings were
      repeated, and additional motor performance tests were also performed. Group B
      carried out only the motor performance tests. The groups exchanged programmes the
      following week. The 1-h strength training session decreased the isometric muscle
      strength of wrist flexion by 18% (P < 0.001) and extension by 18% (P < 0.001) in
      group A, while in group B flexion strength decreased by 19% (P < 0.001) and
      extension strength by 17% (P < 0.001). All the measured EMG activations also
      decreased in both groups. There were no statistically significant differences in
      the results of the motor performance tests between the mean values of the three
      baseline measurements and the values recorded after the training session. The
      result was surprising, but straightforward; neuromuscular fatigue induced by a 1
      h strength training session of the upper extremities had no effect on the motor
      performance functions of the hand, as indicated by reaction times, speed of
      movement, tapping speed and coordination, in these normal healthy female
      volunteers.

PMID- 10208246
TI  - Different metabolic adaptation of heart and skeletal muscles to moderate
      intensity treadmill training in the rat.
AB  - The effect was investigated of treadmill training of moderate intensity on the
      fatty acid-binding protein (FABP) content in relation to parameters of oxidative
      and glycolytic metabolism. To this end, the cytoplasmic FABP content and the
      activity of beta-hydroxyacyl-coenzyme A dehydrogenase (HAD), citrate synthase
      (CS), and 6-phosphofructokinase (PFK) were measured in heart, fast-twitch
      extensor digitorum longus (EDL) and slow-twitch soleus muscles (SOL) of male
      Wistar rats. To investigate the influence of the amount of training (defined as
      the product of exercise duration, intensity and frequency), two training groups
      were created that differed in training frequency (HF, high frequency 5 days x
      week(-1), n = 9; LF, low frequency 2 days x week(-1), n = 9; the exercise being
      20 m x min(-1) for 2 h with no gradient, over 6 weeks) and compared with SC,
      sedentary controls (n = 7). In heart muscle, the cytoplasmic FABP content was 34%
      higher in HF than in SC but was the same as in LF. The CS and HAD activities were
      no different in the three groups, suggesting that the capacity to oxidize fatty
      acids (FA) was not affected by training. The PFK activity was higher (43%) in HF,
      suggesting a shift towards carbohydrate utilization. The FABP content and HAD
      activity did not change in SOL and EDL after training whereas the CS activity
      increased (27%) in SOL and decreased (21%) in EDL in both training groups. In
      addition, PFK activity in EDL was much higher (113%) in the HF than in SC group.
      The HF training was associated with a fine-tuning of FA availability and use in
      heart muscle, and with a more efficient energy production. It is suggested
      therefore that cytoplasmic FABP could be an early marker of muscle adaptation to
      training in heart but not in skeletal muscle. The training reinforced the
      metabolic profile of the skeletal muscles, in particular that of the fast-twitch
      glycolytic muscle. We concluded that a large amount of training is needed when
      the effect on both oxidative and glycolytic parameters is to be studied.

PMID- 10208248
TI  - Sex difference in plasma ammonia but not in muscle inosine monophosphate
      accumulation following sprint exercise in humans.
AB  - Since accumulation of ammonia in plasma has been shown to be lower in females
      than in males following sprint exercise, we hypothesised that muscle inosine
      monophosphate (IMP) accumulation would also be smaller in females, especially in
      type II fibres. A relationship between plasma ammonia and muscle IMP accumulation
      was expected, since ammonia and IMP are formed in equimolar amounts during the
      net breakdown of adenine nucleotides. The sprint-exercise-induced IMP
      accumulation, measured in biopsies from vastus lateralis muscle, did not differ
      between males (n = 16) and females (n = 16) either in type I fibres [males 4.6
      (SD 3), females 5.7 (SD 2) mmol x kg(-1) dry muscle], type II fibres [males 13.2
      (SD 4), females 12.6 (SD 4) mmol x kg(-1) dry muscle] or in mixed muscle [males
      8.4 (SD 3), females 8.2 (SD 3) mmol x kg(-1) dry muscle]. The accumulation of
      plasma ammonia following the sprint was 35% lower in the females than in the
      males. The inter-individual variation in plasma ammonia accumulation was
      explained by the sex but not by the muscle IMP accumulation as tested in a
      multiple regression analysis. In conclusion, the smaller plasma ammonia
      accumulation following sprint exercise in females than in males would seem not to
      be explained by a smaller muscle IMP accumulation per unit muscle during sprint
      exercise.

PMID- 10208247
TI  - Effects of acute hypobaric hypoxia on the appearance of ingested deuterium from a
      deuterium oxide-labelled carbohydrate beverage in body fluids of humans during
      prolonged cycling exercise.
AB  - To determine whether or not acute hypobaric hypoxia alters the rate of water
      absorption from a carbohydrate beverage ingested during exercise, six men cycled
      for 80 min on three randomly assigned different occasions. In one trial, exercise
      was performed in hypoxia (barometric pressure, P(B) = 594 hPa, altitude 4,400 m)
      at an exercise intensity selected to elicit 75% of the individual's maximal
      oxygen uptake (VO2max) previously determined in such conditions. In the two other
      experiments, the subjects cycled in normoxia (P(B) = 992 hPa) at the same
      absolute and the same relative intensities as in hypoxia, which corresponded to
      55% and 75%, respectively, of their VO2max determined in normoxia. The subjects
      consumed 400 ml of a 12.5% glucose beverage just prior to exercise, and 250 ml of
      the same drink at 20, 40 and 60 min from the beginning of exercise. The first
      drink contained 20 ml of deuterium oxide to serve as a tracer for the entry of
      water into body fluids. The heart rate (HR) during exercise was higher in hypoxia
      than in normoxia at the same absolute exercise intensity, whereas it was similar
      to HR measured in normoxia at the same relative exercise intensity. Both in
      normoxia and hypoxia, plasma noradrenaline concentrations were related to the
      relative exercise intensity up to 40 min of exercise. Beyond that duration, when
      exercise was performed at the highest absolute power in normoxia, the
      noradrenaline response was higher than in hypoxia at the same relative exercise
      intensity. No significant differences were observed among experimental
      conditions, either in temporal profiles of plasma D accumulation or in
      elimination of water ingested in sweat. Conversely, elimination in urine of the
      water ingested appeared to be related to the severity of exercise, either high
      absolute power or the same relative power combined with hypoxia. We concluded
      that water absorption into blood after drinking a 12.5% glucose beverage is not
      altered during cycling exercise in acute hypobaric hypoxia. It is suggested that
      the elimination of water ingested in sweat and urine may be dependent on local
      circulatory adjustments during exercise.

PMID- 10208249
TI  - Physiological factors in stretcher carriage performance.
AB  - In this study we examined the anthropometric and physiological factors that may
      account for the ability to carry a casualty on a stretcher. Eleven young soldiers
      were pretested to obtain their anthropometry, body composition, physical fitness,
      and muscle cross-sectional areas. They then performed a two-person manual carry
      of a stretcher containing an 82-kg manikin while walking on a treadmill at a
      speed of 4.8 km/h. Subjects walked until volitional fatigue, as indicated by
      slippage of the stretcher from their hands. Average (SD) carriage time was
      2.7(1.4) min with a range of 1.4-6.4 min. A stepwise multiple linear regression
      revealed that forearm bone-plus-muscle cross-sectional area, thigh muscle cross
      sectional area, and push-up performance accounted for most of the variance in
      hand carriage time (r2 = 0.99, P < 0.001). These data suggest that muscle cross
      sectional area and upper-body muscular endurance are important physiological
      factors in the ability to carry a loaded stretcher by hand.

PMID- 10208250
TI  - Profiles of musculoskeletal development in limbs of college Olympic weightlifters
      and wrestlers.
AB  - To investigate the event-related profiles of musculoskeletal development in
      weight-categorized athletes, we measured the cross-sectional areas (CSA) of bone
      and muscle in the forearm, upper arm, lower leg and thigh, using a B-mode
      ultrasound apparatus, in college Olympic weightlifters (OWL, n = 19) and
      wrestlers (WR, n = 17) and untrained men (UM, n = 24), whose body masses were
      within the range from 55 kg to 78 kg. Both bone and muscle CSA at all sites were
      significantly correlated to the two-thirds power of fat-free mass (FFM(2/3)) with
      correlation coefficients of 0.430-40.741 (P < 0.05) and 0.608-0.718 (P < 0.05),
      respectively. Moreover, there were significant correlations between bone and
      muscle CSA at all sites (r = 0.664-0.829, P < 0.05). Even when bone and muscle
      CSA were expressed relative value to FFM(2/3), both OWL and WR showed
      significantly greater values than UM at all sites except for the lower leg.
      Furthermore, the comparison of the lean (bone + muscle) CSA ratio from site to
      site indicated a higher distribution of lean tissues in the upper extremities in
      OWL and WR compared to UM. While there was no significant difference between the
      two athlete groups in FFM(2/3), OWL showed significantly larger values than WR in
      the bone CSA of the upper arm and thigh and in the muscle CSA of the lower leg
      and thigh. However, lean CSA ratios of the upper extremities to the lower ones
      were significantly higher in WR than in OWL. Thus, the present results indicated
      that, compared to UM, OWL and WR had a greater lean tissue CSA in limbs,
      especially in the upper extremities, even when the difference in FFM was
      normalized. Moreover, the relative distribution of lean tissues in limbs differed
      between the two weight-categorized athletes in spite of there being no difference
      in FFM, which may be attributable to their own training regimens and/or
      competition style.

PMID- 10208251
TI  - Effect of endurance training on the phospholipid content of skeletal muscles in
      the rat.
AB  - Only few data are available on the effect of training on phospholipid metabolism
      in skeletal muscles. The aim of the present study was to examine the effect of 6
      weeks of endurance training on the content of particular phospholipid fractions
      and on the incorporation of blood-borne [14C]-palmitic acid into the
      phospholipids in different skeletal muscles (white and red sections of the
      gastrocnemius, the soleus and the diaphragm) of the rat. Lipids were extracted
      from the muscles and separated using thin-layer chromatography into the following
      fractions: sphingomyelin, phosphatidylcholine, phosphatidylserine,
      phosphatidylinositol, phosphatidylethanolamine, cardiolipin and neutral lipids
      (this fraction being composed mostly of triacylglycerols). It was found that
      training did not affect the content of any phospholipid fraction in soleus
      muscle. It increased the content of sphingomyelin in white gastrocnemius muscle,
      cardiolipin and phosphatidylethanolamine in red gastrocnemius muscle and
      phosphatidylinositol in white gastrocnemius muscle and diaphragm. The total
      phospholipid content in red gastrocnemius muscle of the trained group was higher
      than in the control group. Training reduced the specific activity of
      sphingomyelin and cardiolipin in all muscles, phosphatidylcholine in soleus, red,
      and white gastrocnemius muscles, phosphatidylserine in all muscles,
      phosphatidylinositol in all except the soleus muscle, and
      phosphatidylethanolamine in hindleg muscles, but not in the diaphragm compared to
      the corresponding values in the sedentary group. It was concluded that endurance
      training affects skeletal muscle phospholipid content and the rate of
      incorporation of the blood-borne [14C]palmitic acid into the phospholipid
      moieties.

PMID- 10208252
TI  - Optimal pedalling velocity characteristics during maximal and submaximal cycling
      in humans.
AB  - The aim of this study was to compare optimal pedalling velocities during maximal
      (OVM) and submaximal (OVSM) cycling in human, subjects with different training
      backgrounds. A group of 22 subjects [6 explosive (EX), 6 endurance (EN) and 10
      non-specialised subjects] sprint cycled on a friction-loaded ergometer four
      maximal sprints lasting 6 s each followed by five 3-min periods of steady-state
      cycling at 150 W with pedalling frequencies varying from 40 to 120 rpm. The OVM
      and OVSM were defined as the velocities corresponding to the maximal power
      production and the lowest oxygen consumption, respectively. A significant linear
      relationship (r2 = 0.52, P < 0.001) was found between individual OVM [mean 123.1
      (SD 11.2) rpm] and OVSM [mean 57.0 (SD 4.9) rpm, P < 0.001] values, suggesting
      that the same functional properties of leg extensor muscles influence both OVM
      and OVSM. Since EX was greater than EN in both OVM and OVSM (134.3 compared to
      110.9 rpm and 60.8 compared to 54.0 rpm, P < 0.01 and P < 0.05, respectively) it
      could be hypothesised that the distribution of muscle fibre type plays an
      important role in optimising both maximal and submaximal cycling performance.

PMID- 10208253
TI  - The effects of alterations in dietary carbohydrate intake on the performance of
      high-intensity exercise in trained individuals.
AB  - This study was designed to examine the effects of alterations in dietary
      carbohydrate (CHO) intake on the performance of high-intensity exercise lasting
      approximately 10 min (EXP 1) and 30 min (EXP 2). Trained subjects exercised to
      exhaustion on four occasions on a cycle ergometer at 90% of maximal oxygen
      consumption (VO2max; EXP 1, n = 5) and 80% of VO2max (EXP 2, n = 7). The first
      two tests were familiarisation trials and were carried out following the
      subjects' normal diet. Normal training was continued but standardised during the
      periods of dietary control. The subsequent two tests were performed 2 weeks apart
      after 7 days of dietary manipulation. The two diets were a 70% and a 40% CHO
      diet, isoenergetic with each subject's normal diet and administered in a
      randomised order. At both exercise intensities, time to exhaustion following the
      high CHO and low CHO diets was not different [mean (SD) EXP 1: 11.56 (3.78) min
      and 8.95 (2.35) min, P = 0.22; EXP 2: 26.9 (7.4) min and 26.5 (6.5) min, P =
      0.90]. No differences in resting blood metabolite concentrations were found apart
      from a lower beta-hydroxybutyrate (beta-HB) level following the high CHO diet in
      EXP 2. Blood lactate was higher after exercise at 90% of VO2max following the
      high CHO diet. Blood lactate was higher, and beta-HB lower during exercise at 80%
      of VO2max following the high CHO diet. No differences were found in the other
      blood metabolites tested. The respiratory exchange ratio after 15 min of exercise
      at 80% of VO2max was higher on the high CHO diet. No differences in oxygen
      uptake, heart rate (EXP 2) or ratings of perceived exertion (both experiments)
      were found between conditions. These results indicate that moderate changes in
      diet composition during training do not affect the performance of high-intensity
      exercise in trained individuals when the total energy intake is moderately high.

PMID- 10208254
TI  - Effects of hindlimb suspension and androgen treatment on testosterone receptors
      in rat skeletal muscles.
AB  - This study tested the specific and combined effects of testosterone treatment and
      hindlimb suspension (HS) on the properties of steroid receptors in skeletal
      muscle. Male rats were either administered weekly high doses of testosterone
      heptylate (10 mg x kg(-1)) or olive oil placebo, and were either tail-suspended
      or acted as controls. After 3 weeks of treatment, three muscles were excised from
      each animal, soleus (SOL), extensor digitorum longus (EDL), and plantaris. The
      results showed that the testosterone treatment was unable to minimise the HS
      induced atrophy of skeletal muscle. As expected, HS altered the fibre-type
      composition of SOL muscles (-33% of type I, +188% and +161% of type IIa and
      intermediate fibres respectively, P < 0.01). No overall effect of treatment was
      detected on the fibre-type composition of either slow or fast-twitch muscles.
      Binding capacity determined by a radiocompetition technique was increased by HS,
      especially in SOL and EDL muscles (P < 0.01), while HS or steroid treatment
      decreased the affinity of the steroid receptors. The combination of HS and
      testosterone administration resulted in a decrease in binding capacity and
      affinity of steroid receptors in skeletal muscles. Steroid receptors in fast
      twitch muscles exhibited a higher affinity than those in slow-twitch muscles, and
      it is suggested that it is likely that testosterone treatment is more effective
      in fast-twitch than in slow-twitch muscles. It was concluded that the lack of
      preventive effect of testosterone treatment on HS-induced SOL muscle atrophy
      could be explained by both a decrease in steroid sensitivity and the removal of
      mechanical factors.

PMID- 10208255
TI  - Intra-individual variation of plasma lipids and lipoproteins in prepubescent
      children.
AB  - Estimates of the average intra-individual biological variability for plasma
      lipids and lipoproteins differs substantially among published studies. Moreover,
      this topic does not appear to have received consideration in exercise and health
      literature with normal, healthy children as subjects. The purpose of this study
      was, therefore, to determine the short-term, day-to-day variability of the lipid
      lipoprotein profile from 19 children [mean (SD), 11.5 (0.8) years] from 3
      separate venous blood samples. Intra-individual standard deviations, variances
      and coefficients of variance were determined for total cholesterol (TC),
      triacylglycerol (TG), high-density lipoprotein-cholesterol (HDL-C), HDL-C sub
      fractions HDL2 and HDL3, and low-density lipoprotein-cholesterol (LDL-C). The
      intra-individual variation for TC and LDL-C was used to calculate the 95%
      confidence intervals (CIs) around the National Cholesterol Education Programme
      (NCEP 1991) cut-off points. The main finding was that all of the measured blood
      analytes including TC, TG, HDL-C, HDL2, HDL3, and LDL-C varied considerably from
      day-to-day. Coefficients of total variation ranged from 3.5% for HDL3 to 25.4%
      for TG. Classification of individuals using NCEP guidelines was difficult based
      on only one or two blood samples. The magnitude of variation for LDL-C meant that
      a 95% CI could not be constructed around the NCEP borderline-high classification
      from either one or two samples. However, averaging three TC and LDL-C
      measurements increased the likelihood of classification within the 95% CI. The
      results indicate that when using the NCEP guidelines for children and
      adolescents, true concentrations for TC and LDL-C should be based on the mean of
      multiple samples.

PMID- 10208256
TI  - Carbon dioxide storage and nonbicarbonate buffering in the human body before and
      after an Himalayan expedition.
AB  - Before and 7-12 days after an Himalayan expedition CO2 equilibration curves were
      determined in the blood plasma of 12 mountaineers by in vitro and in vivo CO2
      titration; in vivo osmolality changes (delta Osm x deltaPCO2(-1), deltaOsm x
      delta pH(-1), where PCO2 is the partial pressure of CO2) during the latter
      experiments yielded estimates of whole body CO2 storage. In vitro -delta[HCO3-] x
      delta pH(-1) [nonbicarbonate buffer capacity (beta) of blood] was increased 7
      days after descent [before 31.3 (SEM 0.4) mmol x kgH2O(-1), after 38.3 (SEM 3.9)
      mmol x kgH2O(-1); P<0.05] resulting from an increased proportion of young
      erythrocytes; in additional experiments an augmented beta was found in young (low
      density cells) compared to old cells [<1.097 g x ml(-1): 0.216 (SEM 0.028) mmol x
      gHb(-1), >1.100 g x ml(-1): 0.145 (SEM 0.013) mmol x gHb(-1), where Hb is
      haemoglobin; P < 0.02]. In spite of increased Hb mass in vivo delta[CO2total] x
      deltaPCO2(-1) [0.192 (SEM 0.010) mmol x kgH2O(-1) x mmHg(-1)] and -delta[HCO3-] x
      delta pH(-1) [17.9 (SEM 1.0) mmol x kgH2O(-1)] as indicators of extracellular
      beta rose only slightly after altitude (7 days +16%, P<0.02; +7%, NS) because of
      haemodilution. The deltaOsm x deltaPCO2(-1) [0.230 (SEM 0.015) mosmol x kgH2O(-1)
      x mmHg(-1)] remained unchanged. Prealtitude differences in deltaOsm x delta pH(
      1) between hypercapnia [-41 (SEM 5) mosmol x kgH2O(-1)] and hypocapnia [-20 (SEM
      3) mosmol x kgH2O(-1); P<0.01] disappeared temporarily after return since the
      former slope was reduced. The high value during hypercapnia before ascent
      probably resulted from mechanisms stabilizing intracellular pH during moderate
      hypercapnia which were attenuated after descent.

PMID- 10208257
TI  - Immunohistochemical examination of an orbital alveolar soft part sarcoma.
AB  - BACKGROUND: A 32 year-old male patient had a 6-week history of left-sided
      proptosis. Computer tomography revealed a 16x15x15 mm smooth and well-defined
      mass between the optic nerve and the medial and superior rectus muscles in the
      left orbit. METHODS: The tumour was excised via a cranio-medial orbitotomy
      approach. RESULTS: Histopathological examination, immunohistochemistry and
      electron microscopy findings were consistent with an alveolar soft part sarcoma.
      Immunohistochemical staining showed positive immunoreactivity for neuronespecific
      enolase, vimentin, p53 (30%), p21 (10%) and cyclin D1 (20%), and negative
      immunoreactivity for CD45, cytokeratins, S-100 protein, glial fibrillary acidic
      protein, synaptophysin, chromogranin, calcitonin, serotonin, thyreoglobulin,
      desmin, myosin, actin, HMB-45, pRB, p16 and BCL-2. The growth fraction of the
      tumour cells was 3%. At examination 4 years after surgical excision, there was no
      evidence of local recurrence or for metastases. CONCLUSION: Alveolar soft part
      sarcoma of the orbit is a rare malignant tumour best controlled by surgery. The
      unpredictable behaviour of these neoplasms, however, indicates the need for long
      term follow-up.

PMID- 10208258
TI  - Management of acute submacular hemorrhage using recombinant tissue plasminogen
      activator and gas.
AB  - PURPOSE: To assess the effects of intravitreal injection of recombinant tissue
      plasminogen activator (rTPA) and gas on submacular hemorrhage in age-related
      macular degeneration (ARMD). METHODS: Eleven consecutive patients (11 eyes) with
      subretinal hemorrhage due to ARMD involving the fovea with elevation of the
      neurosensory retina were included in this study. Subretinal hemorrhage occured 12
      h to 14 days before onset of therapy. Injection of rTPA through the pars plana in
      a dose of 50 or 100 microg was performed. Gas instillation (0.2-0.4 ml) followed
      rTPA injection, either immediately after injection (7 patients) or during the
      following day (4 patients). RESULTS: After intravitreal injection of rTPA,
      subretinal clots were totally or partially liquefied when treatment started up to
      3 days after onset of bleeding. In all patients treated with 100 microg rTPA a
      large exudative retinal detachment of the inferior retina resulted, which
      reabsorbed spontaneously within 2 weeks. After reattachment of the exudative
      retinal detachment hyperpigmentation of the retinal pigment epithelium was noted.
      Temporary opacification of the vitreous was observed between the 2nd and 7th
      postoperative day in 5 eyes (45.5%). Postoperative visual acuity increased in 5
      patients (45.5%). CONCLUSION: Intravitreal application of rTPA followed by gas
      injection is a sufficient and convenient technique for effective removal of
      freshly formed submacular hemorrhage. Removal is mediated through combined
      enzymatic (rTPA) and mechanical (gas) effects. This technique offers a quick
      recovery of vision in eyes with less severe ARMD.

PMID- 10208259
TI  - Cataract in traffic.
AB  - BACKGROUND: To obtain a driver's licence to drive a private passenger car, the
      binocular visual acuity required is 0.5 or better, and the minimum horizontal
      width of the visual field is 120 degrees . Persons who fulfill these requirements
      can obtain a driver's licence even if they have an eye disease such as cataract.
      However, contrast sensitivity and visual acuity in glare can be considerably
      decreased in eyes with cataract, and this may create a risk factor in traffic.
      METHODS: Examinations of the eyes, visual fields, contrast sensitivity and glare
      sensitivity (visual acuity in glare and macular photostress test) were performed
      for 35 cataract patients aged 60 to 87 years (mean 70.1 years+/-6.1 SD). They had
      cataract in one or both eyes. In spite of the cataract, the visual acuity was >
      or =0.5 in 50 of the eyes. Twenty-two control eyes of persons within the same age
      range were similarly tested. RESULTS: The results in the contrast sensitivity
      test were significantly worse in the cataract eyes than in the control eyes.
      Contrast sensitivity decreased significantly as the visual acuity became worse.
      In the glare test, none of the control eyes lost any of the lines in the visual
      acuity chart. In the cataract eyes, the loss of lines with the highest glare
      varied from 0 to 6 lines (mean 1.4+/-1.5). The recovery time in the macular
      photostress test was longer, but not significantly, in cataract eyes than in
      normal eyes. There was no significant correlation between the loss of visual
      chart lines and visual acuity or between the recovery time in the macular
      photostress test and visual acuity. CONCLUSION: It would be advisable for traffic
      safety if simple tests for contrast and glare sensitivity were added to the
      requirements for a driver's licence, at least for older drivers. The age and test
      result limits should be defined.

PMID- 10208260
TI  - Correlation of quantitative three-dimensional measurements of macular hole size
      with visual acuity after vitrectomy.
AB  - OBJECTIVE: The purpose of the study was to study the relationship of
      postoperative visual outcome with anatomical parameters of macular holes using
      confocal scanning laser tomography and to predict the postoperative visual
      results. DESIGN: Cohort study. INTERVENTION AND PARTICIPANTS: We evaluated the
      eyes of 44 patients undergoing macular hole surgery (10 men and 34 women aged 40
      76 years, mean 59.1 years). All patients showed idiopathic full-thickness stage 3
      macular holes. The duration of symptoms was 1-4 months (mean 2.7 months). MAIN
      OUTCOME MEASURES: The area, volume, mean depth, and maximum depth of the macular
      holes and the areas of cuff and retinal striae were measured using the Heidelberg
      Retina Tomograph preoperatively. RESULTS: All 44 eyes showed closure of the holes
      and flattening of cuff and retinal striae after vitrectomy and gas tamponade.
      Postoperative visual acuity was significantly correlated with the area (r =
      0.822, P<0.0001), volume (r = 0.840, P<0.0001), mean depth (r = 0.842, P<0.0001),
      and maximum depth (r = 0.831, P<0.0001) of the macular holes, area of cuff (r =
      0.625, P<0.0001), and area of retinal striae (r = 0.648, P<0.0001). Multiple
      regression analysis showed that the combination of the preoperative mean depth of
      macular holes and logarithm of preoperative visual acuity was the strongest
      predictor of the postoperative visual acuity. CONCLUSIONS: Postoperative visual
      results vary significantly with the size of macular holes in patients with stage
      3 macular holes of duration 1-4 months. The use of the confocal scanning laser
      tomography may facilitate the evaluation of macular holes before surgery. Ability
      to predict the postoperative visual results would be helpful in treating patients
      with macular holes.

PMID- 10208261
TI  - Posterior sub-Tenon's steroid injections for the treatment of posterior ocular
      inflammation: indications, efficacy and side effects.
AB  - PURPOSE: Posterior sub-Tenon's steroid injections (PSTSI) are a standard drug
      delivery method used for the treatment of chronic uveitis of the posterior
      segment. The aim of this study was to analyse the indications, efficacy and
      complications of PSTSI in the treatment of chronic uveitis. METHODS: During the
      period 1990-1994, 53 (9.5%) of 558 patients (58 eyes) followed up in the uveitis
      clinic received a total of 162 PSTSI of triamcinolone acetonide 40 mg in the
      superior quadrants. Indications for treatment were vision inferior or equal to
      0.7 and/or intolerable visual disturbance. Only patients in whom PSTSI were the
      only treatment parameter changed were analysed. Among the main parameters
      analysed were visual acuity, aqueous laser flare photometry, intraocular pressure
      (IOP) and complications. RESULTS: Anatomical location of uveitis was as follows:
      anterior HLA-B27-related uveitis with CME (1 patient/1 eye), intermediate uveitis
      (28/32), posterior uveitis (10/10) and panuveitis (14/15). Mean duration of
      follow-up was 448+/-57 days. Visual acuity improved significantly from 0.40+/
      0.03 to 0.79+/-0.07, with 59.4% of eyes having a gain of 2-5 Snellen lines and
      18.7% a gain of >5 lines. Mean aqueous flare photometry decreased significantly
      from 29.6+/-3.5 to 13.6+/-2.2 photons/ms. Mean IOP increased significantly from
      13.6+/-0.5 to 18.5+/-0.8 mm Hg with a rise of pressure >8 mm Hg in 23 cases
      (36%), transient in 16 cases, but chronic in 6 cases, needing filtering surgery.
      Partial superior ptosis was seen in two cases and cataract progressed in seven
      cases. CONCLUSION: PSTSI are very effective in restoring visual acuity in chronic
      uveitis of the posterior segment, without systemic complications, but at the
      expense of intraocular hypertension, a complication that was found more
      frequently than expected.

PMID- 10208262
TI  - Noninvasive measurement of the Bayliss effect in retinal autoregulation.
AB  - PURPOSE: The Bayliss effect describes the reaction of smooth muscle cells in the
      arterial wall to changes in blood pressure. A rise in mean arterial blood
      pressure (MAP) causes an autoregulatory myogenic vessel constriction by smooth
      muscle cells in the arterial wall. The responsiveness of retinal vessels to
      changes in MAP were analyzed using the Retinal Vessel Analyzer (RVA). METHODS:
      Continuous measurement of retinal arterial vessels was performed in 40 healthy
      volunteers (age 18-56 years.) over a 9-min period. After a 3-min baseline
      measurement (phase I), isometric exercise caused a rise in MAP over the next 3
      min (phase II). During the last 3 min (phase III) recovery was observed. Blood
      pressure and ECG were documented simultaneously throughout the experiment.
      RESULTS: Exercise caused a significant rise of 22.8 (+/-6.0) mm Hg in MAP (phase
      II vs. phase I: P<0.001). Retinal arterioles showed 5.5% (+/-2.8%)
      vasoconstriction (P<0.001). During phase III vessel diameters returned to normal,
      with no difference from phase I (P = 0.179). CONCLUSION: Noninvasive measurement
      and quantitative analysis of the Bayliss effect in human retinal vessels by means
      of the RVA is possible. Analysis of retinal arterial autoregulation may provide
      valuable insight into pathologic conditions such as diabetic or hypertensive
      retinopathy.

PMID- 10208263
TI  - Comparative study of visual, auditory, and olfactory function in Usher syndrome.
AB  - BACKGROUND: Usher syndrome is a genotypically and phenotypically heterogeneous
      group of autosomal recessive diseases featuring retinitis pigmentosa (RP) and
      sensorineural hearing loss. A general ciliary dysfunction has been suspected
      following reports of a mutated cytoskeletal protein (myosin VIIA) in type IB, and
      preliminary data has suggested an olfactory deficit. The purpose of this study
      was to quantitatively assess olfactory function in Usher syndrome patients and to
      search for a correlation between the degree of impairment of the three sensory
      systems as indication of an underlying ciliary defect. METHODS: 39 patients with
      Usher syndrome (8 type I, 31 type II) were examined. The ophthalmologic protocol
      included patient history, visual acuity, eye morphology, Goldmann perimetry, and
      electroretinography. The ENT protocol included a thorough examination, speech
      recognition test, pure-tone audiometry and an olfactory function test. RESULTS:
      In both groups, visual acuity was typically 20/40, the remaining visual field
      area was small, and the ERG responses were low to non-detectable. Average hearing
      loss was 100% in type I and 40% in type II. Olfactory thresholds were normal
      [median 9.7 (I) and 8.5 (II) vs. 8.5 in the control group]. There were multiple
      significant correlations between parameters of the same organ, but no
      relationship between parameters of different sensory systems. CONCLUSION: Almost
      all Usher syndrome patients in this study had an advanced form of RP. In
      contrast, auditory function differed considerably between type I and type II. An
      impairment of the olfactory system could not be detected, and there was no
      correlation between parameters representing visual function, hearing ability, and
      olfactory sense.

PMID- 10208264
TI  - Improvement of the osteo-odonto-keratoprosthesis according to Strampelli:
      influence of diameter of PMMA cylinder on visual field.
AB  - BACKGROUND: In surgical management of severe corneal scarring, the osteo-odonto
      keratoprosthesis (OOKP) according to Strampelli is recognised as the best choice.
      Nevertheless, the patients are handicapped by a restricted visual field.
      Enlarging the optical cylinder diameter should allow better rehabilitation of the
      patients. PATIENTS AND METHODS: A mathematical model to calculate the theoretical
      maximum visual field according to the length and the diameter of the cylinder of
      a keratoprosthesis was developed. The theoretical values were compared with our
      findings in three OOKP patients operated on in our hospital. RESULTS: The
      theoretical extent of the visual field with a cylinder of 8 mm length is 55 deg
      if the diameter is 3 mm and 62 deg if the diameter is 3.5 mm. The visual fields
      of our OOKP patients in both types of keratoprosthesis are, however, below the
      theoretically calculated values. Implantation of a prosthesis with a diameter of
      3 mm produced horizontal visual fields of 30 and 36 deg in two patients. In one
      patient with a prosthesis diameter of 3.5 mm the field was 53 deg. CONCLUSIONS:
      The diameter of the visual field increases with the diameter and decreases with
      increasing length of the optical cylinder. In OOKP the implantation of a PMMA
      cylinder with a diameter of 3.5 mm is possible. The enlargement of the diameter
      of the optical cylinder leads to significant enlargement of the visual field. The
      size of the cylinder is limited by the diameter of the available root of the
      tooth.

PMID- 10208265
TI  - Macular rotation with and without counter-rotation of the globe in patients with
      age-related macular degeneration.
AB  - BACKGROUND: Macular rotation to treat exudative age-related macular degeneration
      (AMD) involves translocation of the fovea to a site with intact retinal pigment
      epithelium. To avoid the inevitable postoperative cyclotropia we combined this
      procedure with torsional muscle surgery. PATIENTS AND METHODS: In 30 eyes the
      macula was rotated upward by 30-50 degrees following complete artificial retinal
      detachment and a 360 degrees retinotomy. Simultaneous torsional muscle surgery
      was not carried out in the first 8 eyes; in the remaining 22 eyes surgery of the
      oblique muscles was performed alone or in combination with surgery of two or four
      rectus muscles. Simultaneously or later, muscle surgery was performed on the
      fellow eye in 17 of these patients. Three of the eight patients who had no
      primary muscle surgery were operated on later. They had muscle surgery on the
      macular-rotated eye and on the fellow eye. RESULTS: Postoperatively, the silicone
      oil was removed from all but one eye and an intraocular lens implanted in all but
      two eyes. Five eyes developed a postoperative retinal detachment, three of them
      with proliferative vitreoretinopathy. Three other eyes developed a recurrence of
      the choroidal neovascularization. At last examination, 18 of the 30 eyes (60%)
      had a near vision of 0.4 or better, sufficient for the reading of normal
      newsprint. Six of the eight patients who did not undergo muscle surgery reported
      considerable disorientation caused by the postoperative diplopia and cyclotropia.
      The muscle operation, which has been performed in a total of 25 patients,
      conferred complete freedom from complaints in all but one patient. CONCLUSION:
      Macular rotation succeeded in restoring reading vision in about half of cases of
      exudative AMD, at least in the short term. The most serious complication was the
      development of a retinal detachment. The extremely disorienting side effects of
      diplopia and tilted image could be prevented or effectively treated by muscle
      surgery for counter-rotation of the globe, if need be also in the fellow eye.

PMID- 10208266
TI  - Cellular response in rabbit eyes after human fetal RPE cell transplantation.
AB  - BACKGROUND: This study was carried out to study inflammatory and proliferative
      cellular responses in the rabbit eye after subretinal transplantation of human
      fetal retinal pigment epithelial (HFRPE) cells. METHODS: 5-Bromo-2-deoxyuridine
      (BrdU)-labeled HFRPE cells were injected subretinally into rabbit eyes at three
      different concentrations. Macrophage, glial, and proliferative responses of the
      eye tissues were studied by immunohistochemistry and light microscopy at
      different times after the surgery. RESULTS: In transplanted eyes, the HFRPE cells
      were distributed irregularly either as multilayers or monolayers. In eyes
      receiving high-density cell suspensions, retinal breaks were seen. No retinal
      breaks were noted in the eyes receiving low-density HFRPE cell suspensions. The
      highest intensity of inflammatory response was seen at 4-14 days after surgery,
      with greater expression in transplanted eyes receiving high-density cell
      suspensions. The host cellular response was characterized initially by local
      infiltration of the retina and subretinal space by macrophages and glial cells.
      After day 14, a decline in the number of donor cells was noted in all eyes. At
      later stages the host cellular response was characterized mainly by local
      choroidal thickening and infiltration by inflammatory cells. Proliferative
      response was expressed mainly by retinal cells. CONCLUSION: Initial inflammatory
      and proliferative responses after the xenogenic human to rabbit HFRPE cell
      transplantation were expressed by retinal cells with later involvement of the
      choroid. Our results showed a decline in the number of donor cells starting from
      day 14 after the transplantation. This may suggest a possibility of rejection.
      The initial quantity of injected cells may be critical for the intensity of the
      immune and inflammatory responses.

PMID- 10208267
TI  - CuZn superoxide dismutase transgenic retinal transplants.
AB  - BACKGROUND: The morphology of retinal transplants is believed to depend on the
      extent of mechanical disruption of the donor tissue during the surgical procedure
      and on local factors of the host environment. We hypothesized that oxidative
      stress during donor tissue preparation and implantation further affects
      transplant development and investigated the effects of CuZn superoxide dismutase
      (SOD) overexpression on the survival and morphological development of mouse
      embryonic retinal transplants. METHODS: Retinae and livers from embryonic day 14
      15 SOD overexpressing transgenic mice and CBA control mice were harvested under
      sterile conditions. In order to identify transgenic mouse embryos, the embryonic
      livers were analyzed via nondenaturing gel-electrophoresis for the presence of
      the human SOD protein. Neural retinae were transplanted as fragmented tissue into
      the subretinal space of albino BALB/c mice. At 4-8 weeks following
      transplantation, the grafted eyes were fixed in Bouin's solution and processed
      for histological analysis. RESULTS: Both SOD transgenic and control retinal
      transplants had developed all retinal layers except for a ganglion cell layer and
      exhibited a similar extent of rosette formation. Computer-assisted, quantitative
      assessment of retinal graft volumes revealed a significant, around 58% increase
      in size of SOD transgenic transplants compared with controls. CONCLUSIONS:
      Enhanced intracellular SOD levels do not seem to influence retinal transplant
      morphology as detected by light microscopy. However, volumes of the SOD
      transgenic transplants were found to be increased compared to control grafts.

PMID- 10208268
TI  - Effect of heparin on human corneal fibroblast proliferation in vitro with and
      without growth factor stimulation.
AB  - BACKGROUND: The outcome of keratorefractive procedures such as PRK and LASIK is
      limited by the wound-healing process in the corneal stroma, which gives rise to
      complications such as haze formation and regression. The proliferation and matrix
      synthesis of corneal stromal fibroblasts is the central element of the wound
      healing process. In order to develop new therapeutic strategies to reduce wound
      healing intensity, we investigated the effect of heparin on the proliferation of
      cultured human corneal stromal fibroblasts (HCF) alone and in the presence of
      growth factors. METHODS: Primary cultures of HCF were established using
      epithelium and endothelium-free explants. Secondary cultures of HCF (first
      passage), cultured in WM/F12 supplemented with 10 microg/ml transferrin and 10
      microg/ml thyroglobulin (LR-1 medium), 1% fetal calf serum (FCS) and 10% FCS were
      used to determine the effect of heparin on the proliferation of HCF in
      concentrations ranging from 12.5 microg/ml to 5000 microg/ml. Cell number was
      determined using the CASY 1 cell counter system. Modulation of HCF proliferation
      by heparin (50 microg/ml and 2000 microg/ml) was also investigated under serum
      free conditions and in the presence of bFGF, EGF and PDGF-BB. RESULTS: Addition
      of heparin led to a dose-dependent inhibition of proliferation after 6 days of
      incubation, which was statistically significant for 500-5000 microg heparin/ ml
      (FCS 1%) and for 200-5000 microg heparin/ml (FCS 10%). IC50 values for this
      effect were determined to be approximately 700 microg heparin/ml. When cultured
      under serum-free conditions (LR-1), a significant reduction of cell number was
      only observed with 5000 microg heparin/ml. There was no significant modulation of
      PDGF-BB-, bFGF-, or EGF-stimulated cell proliferation by heparin at
      concentrations of 50 microg/ml and 2000 microg/ml after 6 days of incubation.
      CONCLUSION: Our observations indicate that heparin can inhibit proliferation of
      HCF effectively. The results of the present study could eventually pave the way
      to prevent anterior stromal haze formation and regression after keratorefractive
      surgery.

PMID- 10208269
TI  - Leber's hereditary optic neuropathy mitochondrial DNA mutations in familial
      multiple sclerosis.
AB  - Leber's hereditary optic neuropathy (LHON) can be difficult to distinguish from
      optic neuritis due to multiple sclerosis (MS). For several decades an association
      of LHON and MS has been suspected, and within the past 7 years the LHON
      nucleotide (nt)-3460 and nt-11778 mtDNA mutations have been identified in several
      patients with MS-like phenotypes. To further study this association, we tested 42
      index patients with clinically definite, familial MS for the LHON mtDNA mutations
      at nt-3460, nt-11778, and nt-14484. No patients had a pathogenic LHON mtDNA
      mutation; however, two MS patients with unilateral optic neuritis harbored the nt
      15257 mtDNA polymorphism that was reported originally as a pathogenic LHON
      mutation. Several investigators have shown evidence that the nt-15257 mtDNA
      mutation is not primarily pathogenic. Therefore, we conclude that pathogenic LHON
      mtDNA mutations are absent or rare in unselected patients with familial,
      clinically definite MS (95% confidence intervals for each of the negative
      mutations 0-7.0%).

PMID- 10208270
TI  - Citation analysis of neuropathology journals.

PMID- 10208271
TI  - Neuroaxonal pathology in Creutzfeldt-Jakob disease.
AB  - Neuroaxonal pathology has met little attention in transmissible spongiform
      encephalopathies. In brains of a series of 39 consecutive Creutzfeldt-Jakob
      disease (CJD) cases, we detected numerous abnormal neurites that labeled for
      neurofilament proteins (NFP) by immunocytochemistry. Three types of abnormally
      NFP-accumulating structures were more prominently observed in CJD brains than in
      age-matched control brains: 1. Neurons with NFP in their somata were seen in 29
      CJD cases (74%), some appearing distended with eccentrically placed nuclei and
      homogenously stained cytoplasm. 2. Neuritic distensions (neuritic swellings,
      dystrophic neurites) were observed mainly in the white matter but also at the
      junction between gray and white matter. In some axons many such swellings could
      be traced along the visible part of the axonal segment. 3. Axonal spheroids were
      observed mainly in the medulla, predominantly but not exclusively in posterior
      nuclei, and were more numerous than in age-matched control brains. Several
      neurons, axons and spheroids demonstrated immunoreactivity for amyloid precursor
      protein. Their number was much smaller, however, than that of NFP-immunoreactive
      structures and varied from one or two immunopositive neurites per section to
      small clusters of beaded or spiral axons. Focal expression of apolipoprotein E in
      cells of microglial and astrocytic morphology was observed in areas with most
      pronounced axonal damage. We conclude that neuroaxonal pathology is a frequent
      and important part of brain lesioning in CJD, probably reflecting profound
      impairment of axonal transport.

PMID- 10208272
TI  - The visualization of a new class of traumatically injured axons through the use
      of a modified method of microwave antigen retrieval.
AB  - Antibodies to the amyloid precursor proteins (APP) have become routine markers
      for detecting traumatically induced axonal injury (AI) in animals and man.
      Unfortunately, the techniques used to visualize these proteins are not compatible
      with routine electron microscopic (EM) analysis. In the current communication, we
      describe a method for the ultrastructural visualization of antibodies to APP and,
      using this method, we identify a previously unrecognized population of
      traumatically injured axons. Rats were subjected to an impact acceleration
      traumatic brain injury and allowed to survive 30 min to 3h postinjury. The
      animals were then perfused, their brains sectioned on a vibratome and the
      sections prepared for immunocytochemistry using a computer-controlled microwave
      capable of temperature regulation. The use of temperature-controlled microwave
      energy unmasked APP antigenic epitopes without sacrificing ultrastructural
      detail. The APP antibody was found in two distinct populations of reactive axons
      that differed in size, morphology, location, and temporal progression. Comparable
      to previous descriptions, one population showed traumatically related reactive
      changes that led to swelling and disconnection. The other population, however,
      revealed unanticipated changes reflected in nodal and paranodal swelling of small
      continuous fibers that showed no evidence of disconnection during the time
      periods assessed. These studies provide new insight into the complexity of the
      pathobiology of AI, while describing a novel approach for enhancing APP
      immunoreactivity at the EM level.

PMID- 10208274
TI  - Genotyping of the prion protein gene at codon 129.
AB  - Sporadic, iatrogenic and new variant forms of Creutzfeldt-Jakob disease are
      associated with a predisposition for disease depending on a homozygosity at amino
      acid residue 129 of the prion protein gene (PRNP). A novel polymerase chain
      reaction/restriction digestion assay to screen for this polymorphism was
      developed and proved after comparison with a previously used method to be
      advantageous. Furthermore, for prevention of incorrect results an internal
      control for the restriction digestion was constructed. The feasibility of this
      method was tested in a cohort of 300 healthy Caucasian subjects. Of this normal
      population, 48.7% were heterozygous at codon 129, 43% homozygous for methionine
      and 8.3% for valine.

PMID- 10208273
TI  - Mitochondrial enzyme expression in the hippocampus in relation to Alzheimer-type
      pathology.
AB  - Recent reports have suggested that mitochondrial dysfunction may contribute to
      the progression of the pathology of Alzheimer's disease (AD). However, both
      increases and decreases in the activity of cytochrome oxidase have been described
      in the hippocampi of AD patients. In this study we used immunohistochemistry and
      quantitative autoradiographic methods to study the expression pattern of two
      cytochrome oxidase subunit proteins (nuclear-encoded COX IV and mitochondrial
      encoded COX I) in the hippocampus in relation to the development of AD-type
      pathology. We found heterogeneous expression of both COX subunits in AD with an
      increased expression of both subunit proteins in healthy, non-tangle-bearing,
      neurones but absence of both subunit proteins in tangle-bearing neurones. Levels
      of COX IV but not of COX I were related to the amount of hyperphosphorylated tau
      accumulated in the same hippocampal region but not to the amount of amyloid
      deposited in sporadic AD. In Down's syndrome COX I and COX IV were similarly
      increased in the presence of AD pathology in non-tangle-bearing neurones.
      However, in these cases levels of enzyme expression were correlated to the amount
      of amyloid accumulation but not the amount of hyperphosphorylated tau in the
      hippocampus. We believe that heterogeneity of expression of mitochondrial enzyme
      proteins between neurones may contribute to the conflicting conclusions in
      previous reports regarding relative levels of cytochrome oxidase activity in the
      hippocampus in AD. We hypothesise that the increased mitochondrial enzyme
      expression in healthy-appearing neurones of AD brains may represent a
      physiological response to increased functional demand on surviving neurones as a
      consequence of AD-related neuronal pathology.

PMID- 10208275
TI  - Progressive parenchymal deposition of beta-amyloid precursor protein in rat brain
      following global cerebral ischemia.
AB  - In addition to producing acute neuronal necrosis within selectively vulnerable
      brain regions, our recent studies have shown that global cerebral ischemia may
      also be followed by protracted degenerative changes occurring over the course of
      10 weeks. Chronic brain pathology may be associated with the abnormal deposition
      of beta-amyloid precursor protein (betaAPP). In the present study, we used a
      monoclonal antibody to the N-terminal portion of betaAPP to characterize the
      brains of rats surviving 1-10 weeks following 10 min of global brain ischemia
      produced by bilateral carotid artery occlusions plus systemic hypotension. After
      ischemia, increased betaAPP immunolabeling emerged in several brain regions. In
      the hippocampus, granular deposits appeared in the damaged CA1 area by 2 weeks,
      and by 4-10 weeks the remnants of necrotic CA1 neurons were also immunolabeled.
      In striatum and thalamus, regions with necrotic cell death also revealed granular
      betaAPP deposits. The neocortex was devoid of overt ischemic neuronal damage but
      revealed prominent betaAPP immunoreactivity. Large ovoid deposits of low-density
      betaAPP immunostaining occurred in cortical neurons at 1-2 weeks. At 4-10 weeks,
      large round or oval deposits immunoreactive for betaAPP appeared in several
      cortical regions. The highest density of deposits was seen in the temporal and
      piriform cortices. Our results indicate that abnormal betaAPP deposition may
      result from ischemic as well as chronic neurodegenerative processes.

PMID- 10208276
TI  - Peripheral nerve structure and function in long-term galactosemic dogs:
      morphometric and electron microscopic analyses.
AB  - Experimental galactosemia for activating the polyol pathway is used extensively
      to explore the pathogenesis of diabetic complications. However, despite the
      presence of severe neuropathy in galactosemic rats, changes in the peripheral
      nerve have not been well established in galactosemic dogs. We therefore conducted
      biochemical, electrophysiological, and morphometric studies on peripheral nervous
      systems (PNS) in dogs given a 30% galactose diet for 44 months. Age- and sex
      matched dogs given a 30% cellulose diet were used as control. Chronic
      galactosemia resulted in accumulation of galactitol and decrease in myo-inositol
      in the sciatic nerve. Electrophysiological and teased fiber analyses demonstrated
      no significant abnormalities in the ulnar and peroneal nerves in galactosemic
      dogs. Morphometric analyses revealed a tendency of myelinated fiber atrophy (24%
      reduction of average fiber size) associated with 20% decrease (P < 0.05 vs
      control) in mean myelinated fiber occupancy rate in the peroneal nerve in
      galactosemic dogs. In the anterior mesenteric ganglion, there was a slight but
      significant increase (8%) in mean neuronal cell size in galactosemic dogs (P <
      0.05 vs control). Electron microscopy revealed that galactosemia did not produce
      dystrophic and degenerative changes in the autonomic ganglion in dogs. We
      conclude that structural and functional changes in the PNS of galactosemic dogs
      are mild and different from those of the rat model. These findings suggest that
      the severity of peripheral neuropathy induced by chronic galactosemia may be
      species dependent.

PMID- 10208277
TI  - Xanthogranuloma of the sellar region: a clinicopathological entity different from
      adamantinomatous craniopharyngioma.
AB  - Xanthogranulomatous change of craniopharyngioma, consisting of cholesterol
      clefts, macrophages, chronic inflammatory infiltrates, necrotic debris and
      hemosiderin deposits, has been traditionally considered a hallmark of the
      adamantinomatous variant, even in the absence of epithelium. Based on a series of
      110 craniopharyngioma patients undergoing primary surgery, we found 37 specimens
      with a predominating xanthogranulomatous component. Only 3 of these cases (8%)
      exhibited additional histological features of adamantinomatous craniopharyngioma,
      while 13 cases (35%) contained non-adamantinomatous epithelium composed of
      squamous or ciliated cuboidal cells. Subsequent clinical analysis revealed that
      these 37 xanthogranulomatous lesions differed from 59 classical adamantinomatous
      craniopharyngiomas with respect to preferential occurrence in adolescents and
      young adults (mean age 27 years), predominant intrasellar location, smaller tumor
      size, more severe endocrinological deficits, longer preoperative history, lower
      frequency of calcification and visual disturbances, better resectability, and a
      more favorable outcome. On the other hand, xanthogranulomatous and
      adamantinomatous lesions did not differ with respect to sex, amount of cystic
      components, or the intraoperative aspect, considered by the neurosurgeon as being
      typical for craniopharyngioma in all cases. We suggest that xanthogranuloma
      (cholesterol granuloma) of the sellar region is clinically and pathologically
      distinct from the classical adamantinomatous craniopharyngioma.

PMID- 10208278
TI  - Reactive microglia in aging and dementia: an immunohistochemical study of
      postmortem human brain tissue.
AB  - Significantly increased up-regulation of HLA DR (major histocompatibility complex
      class II antigen) was seen using immunohistochemistry in postmortem brain tissue
      from demented patients with Alzheimer's disease (AD) (73 cases, 61 females/12
      males, mean age 84 +/- 9 years) compared to controls (22 cases, 10 females/12
      males, mean age 78 +/- 9 years). The counts of HLA DR-expressing activated
      microglia were significantly higher in female AD patients compared to males,
      significantly higher in AD patients with the age at death greater than 75 years
      compared to those dying younger and higher, although not statistically
      significantly, in AD patients with the apolipoprotein E (ApoE) epsilon4 allele
      compared to those patients not carrying this allele. In contrast to the situation
      in AD patients, in the control cases the HLA DR expression was higher in males
      compared to females. Furthermore, in the very old non-demented patients (age at
      death > 80 years), a decrease in the up-regulation of HLA DR expression was
      observed. A significant correlation between activated microglia and
      neurofibrillary tangles was seen in female AD patients compared to males, in AD
      cases without ApoE epsilon4 allele compared to those with this allele, in
      sporadic cases compared to familial and in cases with senile rather than
      presenile onset of the disease. Our results indicate that there is an age- and/or
      sex-related variability in up-regulation of HLA DR expression of microglia and
      that the linkage between this up-regulation and AD lesions is significantly
      influenced by the ApoE epsilon4 allele, gender of subjects, age at onset and
      familiality of the disease.

PMID- 10208279
TI  - Expression of stem cell factor and c-kit receptor in neural cells after brain
      injury.
AB  - Previously it has been shown that c-kit receptor (c-kitR) and its ligand, stem
      cell factor (SCF), are expressed in the central nervous system. We have reported
      that SCF in cultures regulates mouse microglial function. Here we demonstrate
      that SCF/c-kitR signaling also takes place in situ. We used a penetrating stab
      wound injury as a model and analyzed the SCF and c-kitR expression in neural
      cells by immunohistochemistry and in situ hybridization. We found that microglia
      activated by injury up-regulated c-kitR expression, whereas some astrocytes in
      the vicinity of the wound expressed SCF mRNA in addition to neurons. This
      observation suggests that SCF/c-kitR signaling between neurons, astrocytes and
      microglia also occurs in situ.

PMID- 10208280
TI  - Cell surface aggregation of elastin receptor molecules caused by suramin
      amplified signals leading to proliferation of human glioma cells.
AB  - We have recently shown that glioma cell lines, as well as cells of human
      malignant gliomas in situ, synthesize tropoelastin. In addition, glioma cells
      degrade tropoelastin using metalloproteinase(s), and the resulting peptides,
      incapable of assembling in the extracellular fibers, interact with the 67-kDa
      cell surface elastin binding protein (EBP), to transduce signals leading to up
      regulation of cell proliferation. In this report, we show that exposure to the
      polysulfonated bis-naphthylurea suramin causes accumulation of physiologically
      active EBP molecules on the cell surface of a panel of glioma cell lines (U87,
      MG, U251 MG, U343 MG-A, U373 MG, SF 126, SF188, SF539), which results in an
      increase of cellular attachment to elastin-coated dishes and in an efficient
      binding of radiolabeled tropoelastin. Moreover, 100-200 microM suramin stimulates
      [3H]-thymidine incorporation by those tropoelastin-producing glioma cell lines,
      but not by A 2058 melanoma cells, which do not produce elastin. Treatment of all
      glioma cell lines with 100 microM suramin consistently increased expression of
      cyclin A and its cyclin-dependent kinase, cdk 2, to levels reached following the
      exposure to exogenous elastin-degradation products (kappa-elastin). Our data
      suggest that a suramin-stimulated accumulation of EBP molecules on the cell
      surface of glioma cells amplifies the elastin-derived signals, leading to their
      progression through the cell cycle.

PMID- 10208281
TI  - Cell death and apoptosis regulating proteins in Parkinson's disease--a cautionary
      note.
AB  - We studied the substantia nigra of three Parkinson's disease (PD) patients and
      three age-matched individuals by in situ DNA-end labeling (ISEL) and
      immunohistochemistry for the apoptosis regulating proteins Bcl-2, Bax and Bcl-x
      on 50 consecutive sections per patient. No melanin-containing cell was identified
      with typical apoptotic changes in either patient or control substantia nigra.
      With prolonged reaction-time the terminal transferase-mediated DNA-end labeling
      revealed a signal in 2.0 +/-1.2% melanin-containing cells in PD compared to 1.3
      +/-1.1% in control. This difference did nor reach statistical significance and no
      condensation or margination of the chromatin was evident. No significant changes
      of any of the apoptosis regulating proteins were apparent in PD substantia nigra.
      These findings do not support the hypothesis that apoptosis plays a central role
      in the pathogenesis of PD.

PMID- 10208282
TI  - Is there apoptosis in Lewy body disease?

PMID- 10208283
TI  - Adult Leigh syndrome with mitochondrial DNA mutation at 8993.
AB  - Adult onset Leigh syndrome with a nucleotide (nt) 8993 mutation in mitochondrial
      (mt) DNA is reported. A 43-year-old woman with a 6-year-history of insulin
      resistant diabetes mellitus developed muscular weakness, intractable nausea and
      vomiting, and anemia. These were followed vertigo, blindness, and deafness with
      nystagmus. Magnetic resonance imaging (MRI) revealed abnormal high intensities in
      the bilateral medial regions of the thalamus and periaqueductal gray matters.
      Autopsy disclosed well-demarcated necrotizing lesions with prominent capillaries
      in the areas detected by MRI, which were sufficiently diagnostic for Leigh
      syndrome. MtDNA analysis performed on DNAs extracted from formalin-fixed tissues
      including liver, heart, brain, muscle, kidney and pancreas showed a T-->G
      mutation at nt 8993. This is the first case of adult Leigh syndrome demonstrating
      on mtDNA mutations.

PMID- 10208284
TI  - Multiple system atrophy with remarkable frontal lobe atrophy.
AB  - The autopsy findings of a multiple system atrophy (MSA) patient with remarkable
      frontal lobe atrophy are described. The patient was a 65-year-old woman with a 13
      year history of untreatable parkinsonism, dysautonomia and progressive motor
      aphasia. The brain weight was 810 g, and there was remarkable atrophy of the
      cerebrum predominantly in the frontal lobe, striatum, pons and cerebellum.
      Microscopic examination revealed a preserved cortical structure with laminar
      gliosis in the sixth layer of the precentral and superior frontal gyri of the
      frontal lobe, and postcentral gyrus and inferior parietal lobule of the parietal
      lobe. The second layer of the cortices of these regions were also revealed to be
      in a spongy state, and mild cell loss was seen in the fifth and six layers. The
      frontal lobe white matter showed a mild loss of myelinated fibers and axons, and
      mild gliosis. Glial cytoplasmic inclusions (GCIs) were abundantly observed in the
      deep layer of the cortex in the regions mentioned above, and were more abundant
      in the white matter of the frontal and parietal lobes, callosal body, and
      internal, external and extreme capsules. There was severe degeneration in the
      olivopontocerebellar and striatonigral systems, and GCIs in widespread regions of
      the brain. No Pick bodies, Lewy bodies, ballooned neurons, senile plaques, or
      significant amounts of neurofibrillary tangles were detected. There were no
      vascular changes. Thus, this was a verified MSA patient with progressive aphasia
      and remarkable frontal lobe atrophy. We indicate a possible involvement of the
      cerebral lobes in MSA.

PMID- 10208285
TI  - Vascular endothelial growth factor (VEGF) likely contributes to oligodendroglioma
      angiogenesis.

PMID- 10208286
TI  - Influence of melatonin upon the protective action of conventional anti-epileptic
      drugs against maximal electroshock in mice.
AB  - Melatonin (50 mg/kg; 60 min before the test) significantly raised the
      electroconvulsive threshold in mice. The protective action of melatonin (50
      mg/kg) in the electroconvulsive threshold test was reversed by aminophylline,
      picrotoxin and bicuculline. Melatonin at the subconvulsive dose of 25 mg/kg
      potentiated the anticonvulsive activity of carbamazepine and phenobarbital (ED50
      values were significantly decreased from 12.1 to 8.3 and from 18.9 to 11.8 mg/kg,
      respectively). No potentiation was observed in the case of valproate and
      diphenylhydantoin (their ED50s were changed from 253 to 249 and from 10.3 to 9.7
      mg/kg, respectively). Melatonin did not influence the plasma or brain levels of
      anti-epileptics studied, so a pharmacokinetic interaction is not probable.
      Melatonin (25 mg/kg) alone and its combinations with carbamazepine or
      phenobarbital, providing a 50% protection against maximal electroshock, were
      devoid of significant motor adverse effects, but caused strong long-term memory
      deficit. Consequently, it does not seem to be a good candidate for the treatment
      of epilepsy.

PMID- 10208287
TI  - A double-blind crossover comparison of clomipramine and desipramine in the
      treatment of panic disorder.
AB  - OBJECTIVE: To compare the efficacy of clomipramine hydrochloride (CMI), a
      serotonin reuptake inhibitor with the noradrenergic tricyclic antidepressant
      agent, and desipramine hydrochloride (DMI) for patients with panic disorder (PD).
      METHOD: Following a 2-week, single-blind placebo washout phase, 17 PD outpatients
      completed a 16-week, double-blind, crossover comparison of CMI and DMI. Key
      outcome measures included panic attacks frequency, the NIMH Global Scales for
      Anxiety, Depression and Impairment, Hamilton Anxiety Scale (Psychic and Somatic
      Subscales), Zung Anxiety Inventory (Raw and Index Subscales) and the Spielberger
      State Anxiety Scale. RESULTS: Both CMI and DMI led to significant improvement
      from baseline placebo state in panic attacks frequency and behavioral ratings
      (p<0.001). CMI led to a greater reduction in the frequency of panic attacks
      (p=0.028) and was superior to DMI on ratings of anxiety: NIMH Global Anxiety,
      Zung Anxiety Scale (Raw and Index) and the Spielberger Anxiety Scale. No
      difference was found between the drugs on the NIMH Global Impairment Scale and
      the Hamilton Somatic and Psychic Scales. CONCLUSION: Both drugs appeared to have
      significant therapeutic effects in patients with PD, but CMI appeared to be more
      effective. The effectiveness of the serotonergic drug suggests that the role of
      the serotonergic system in the pathogenesis of PD should be further explored.

PMID- 10208289
TI  - Alterations of corticotropin releasing hormone (CRH) and neuropeptide Y (NPY)
      plasma levels in mood disorder patients with a recent suicide attempt.
AB  - In order to receive a further understanding of stress-regulation in depressed
      suicide attempters, peptides that are supposed to be related to the stress system
      (the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system)
      were studied in plasma. When compared with healthy controls, cortisol was high
      (p<0.001) and corticotropin releasing hormone (CRH) and neuropeptide Y (NPY)
      appeared to be low (p<0.001) in patients who had recently attempted suicide.
      Patients who had repeatedly attempted suicide had the lowest NPY. A correlation
      between NPY and cortisol (p<0.05) was found in suicidal patients with depression
      NOS, whereas beta-endorphins correlated with cortisol (p<0.01) in suicidal
      patients with major depressive disorder. A postdexamethasone decrease of NPY was
      noted in the controls but not in the patients. These results suggest stress
      system alterations in suicidal patients with mood disorders.

PMID- 10208290
TI  - Antinociception after both peripheral and intrathecal injection of oxotremorine
      is modulated by spinal nitric oxide.
AB  - The present study investigated the role of spinal nitric oxide (NO) in the
      antinociception induced by intraperitoneal (i.p.) and intrathecal (i.th.)
      injection of oxotremorine. The experiments were carried out on male Wistar rats,
      which had cannulas chronically implanted in the lumbar enlargement of the spinal
      cord. Antinociceptive effects were evaluated using a tail-flick and a paw
      pressure test. To raise the spinal NO level, the rats received the NO donor, 3
      morpholino-sydnonimine (SIN-1, 10 and 100 microg/5 microl); to lower the NO
      level, the inhibitor of NO synthase, N-nitro-L-arginine methyl ester (L-NAME, 50
      and 400 microg/5 microl), was administered. Both those substances were injected
      i.th. Systemic injections of oxotremorine (0.02 and 0.1 mg/kg) produced a
      significant increase in the thermal nociceptive threshold, while the mechanical
      threshold was affected only by the higher dose (0.1 mg/kg) of the muscarinic
      agonist. I.th. injections of oxotremorine (0.1 ng, 1 ng, 1 microg/5 microl)
      produced significant antinociception in both those tests. I.th. administration of
      SIN-1 in doses which themselves did not affect the nociceptive threshold
      antagonized both the peripheral and central oxotremorine antinociception. I.th.
      administration of L-NAME (50 and 400 microg/5 microl) did not change the
      nociceptive threshold, but dose-dependently potentiated the effects of
      oxotremorine injected i.p. in both tests; however, the effect of i.th.
      administration of oxotremorine was potentiated only in the tail-flick test. Our
      results demonstrate that irrespective of the way of its injection, the
      antinociceptive effect of oxotremorine is modulated by activity of the spinal NO.
      Moreover, our results further support the hypothesis that NO present in the
      spinal cord exerts pronociceptive effects.

PMID- 10208288
TI  - Effects of calcium channel blockade on intravenous self-administration of ethanol
      in rats.
AB  - In the present study the involvement of voltage-operated calcium channels (VOCCs)
      in the acquisition and maintenance of operant i.v. ethanol (EtOH) self
      administration was investigated in rats. Rats readily learned to self-administer
      EtOH (unit dose range: 0.5-4% v/v) within five daily 2-h sessions, when infusions
      were made contingent upon nose-poking in a hole containing infrared sensors.
      Response rate was related to the EtOH concentration in an inverted U-shaped
      manner, the maximal rate and intake being observed at a unit dose of 1% v/v (0.27
      mg EtOH/infusion). Self-administration of EtOH appeared to be behaviorally
      specific, as responding in the reinforced hole did not coincide with increased
      responding in a nonreinforced hole. Daily treatment with the dihydropyridine VOCC
      blocker nimodipine (2.5-20 mg/kg, i.p., t-15 min) dose-dependently attenuated
      acquisition of EtOH self-administration; the 5 mg/kg dose resulting in a partial,
      and the 10 and 20 mg/kg doses in a complete prevention of i.v. self
      administration behavior. The effects of nimodipine (2.5-5.0 mg/kg) were
      considered to be relatively specific, as an inhibition of the reinforced
      responding could be demonstrated in the absence of a significant effect on
      nonreinforced responding. When tested in rats showing stable self-administration
      behavior (unit dose: 1% v/v EtOH), nimodipine showed biphasic dose-response
      effects; with 2.5 and 5 mg/kg resulting in a mild increase, and 10 and 20 mg/kg
      resulting in a decrease of self-administration behavior, respectively. The
      present study suggests that blockade of VOCCs attenuates the reinforcing stimulus
      effects of EtOH; and, as such, the data may offer an explanation for the
      previously reported EtOH intake-reducing effects of dihydropyridine calcium
      channel ligands obtained in two-bottle choice paradigms. Dihydropyridine
      derivatives, such as nimodipine, may therefore offer an interesting approach to
      the pharmacotherapy of alcoholism.

PMID- 10208291
TI  - Cholecystokinin and morphine-induced hypothermia.
AB  - The effects of cholecystokinin-8 sulfate (CCK-8), cholecystokinin-8 unsulfate
      (CCK-8U), cholecystokinin-4 (CCK-4), caerulein and morphine on mice core body
      temperature have been studied in the present work. Subcutaneous injection of
      different doses of caerulein (0.05, 0.1 and 0.5 mg/kg), CCK-8 (0.05, 0.1 and 0.25
      mg/kg) and morphine (10, 20 and 30 mg/kg) induced hypothermia. CCK-8U and CCK-4
      did not elicit any response. The hypothermic response induced by caerulein, a CCK
      related decapeptide but not morphine was decreased by selective CCK(A) receptor
      antagonist MK-329. However, the hypothermia induced by morphine but not caerulein
      was reduced by opioid antagonist naloxone. When morphine plus caerulein was
      administered a higher hypothermia was induced. Pretreatment of animals with L-365
      260, a selective CCK(B) receptor antagonist did not alter the hypothermia induced
      by the drugs. The response induced by combination of the both drugs was decreased
      by MK-329. Administration of CCK antagonists MK-329 and L-365 260 to mice did not
      exert any effect on temperature. It is concluded that the CCK(A) receptor
      mechanism may be involved in the hypothermic effect of CCK agonists or morphine,
      while opioid receptor mechanism is not involved in CCK receptor agonists'
      response.

PMID- 10208292
TI  - The development of cross-tolerance between morphine and nicotine in mice.
AB  - In the present study, cross-tolerance between nicotine and morphine in mice has
      been investigated. Mice were treated subcutaneously with three doses of morphine
      (12.5, 25 and 50 mg/kg) once daily, for 3 days in order to produce tolerance to
      morphine and nicotine antinociception. Tolerance only developed in the high dose
      group. On the 4th day, the antinociceptive effect of three test doses of morphine
      (3, 6 and 9 mg/kg) or nicotine (0.01, 0.05 and 0.1 mg/kg) were assessed.
      Tolerance to the responses of both drugs were observed. Intraperitoneal
      administration of nicotine (2 mg/kg) three times a day for a period of 12 days,
      also induced tolerance to the antinociceptive effects of both morphine and
      nicotine. When animals were tested on the 13th day, the antinociceptive responses
      of morphine or nicotine were reduced. Another group of animals was treated with
      low doses of morphine daily (12.5 or 25 mg/kg) plus nicotine (2 mg/kg) three
      times daily for 3 days. In this group of animals, the antinociception to either
      morphine or nicotine was tested. Combination of both drugs caused an increase in
      tolerance to either drug. It is concluded that there is cross-tolerance between
      the two drugs.

PMID- 10208293
TI  - Effect of nicotine on apomorphine-induced licking behaviour in rats.
AB  - In the present study, the dopaminergic receptor agonist apomorphine (0.1, 0.25
      and 0.5 mg/kg) induced a dose-dependent licking in rats. Nicotine administration
      (0.025-250 microg/kg) altered the apomorphine-induced licking. The lower doses of
      nicotine (0.05 and 0.5 microg/kg) increased while the higher dose of the drug
      (250 microg/kg) reduced the apomorphine response. The antimuscarinic drug
      atropine (2.5 and 5 mg/kg) reduced the effects of apomorphine or nicotine plus
      apomorphine. The central nicotinic receptor antagonist mecamylamine (0.05, 0.25
      and 0.5 mg/kg) also reduced the response induced by apomorphine or nicotine plus
      apomorphine. However, the peripheral nicotinic receptor antagonist hexamethonium
      (2.5, 5 and 10 mg/kg) reduced the response induced by nicotine plus apomorphine
      but not that elicited by apomorphine alone. The results indicate that the
      nicotinic receptor mechanism(s) may interact with apomorphine-induced licking in
      rats. Although central nicotinic and cholinergic mechanisms may be involved in
      the licking induced by apomorphine, peripheral nicotinic mechanism may be
      involved in the nicotine-induced increased apomorphine effect.

PMID- 10208294
TI  - Prenatal stress induces body weight deficit and behavioural alterations in rats:
      the effect of diazepam.
AB  - Prenatal stress may induce intrauterine growth retardation, but it is not known
      whether a treatment with the anxiolytic benzodiazepine, diazepam may interfere
      with this phenomenon. A daily physical stress consisting of a forced immersion
      for 15 min in cold water was applied to pregnant rats of the Wistar strain from
      gestational day 5 until parturition. Animals were treated either with
      physiological saline or with diazepam (0.1 or 1 mg/kg/day) injected
      intraperitoneally 1 h prior to stress application. Control animals received
      injections of physiological saline but were not subjected to physical stress.
      Newborn pups subjected to prenatal stress showed reduced body weight as compared
      to control animals. Offspring were also examined for the appearance day of the
      following reflexes: cliff aversion, startle, righting, forelimb placing, forelimb
      grasping and bar holding. Hair growth, and first day of ears and eyes opening was
      also scored. At 60 days of age, male rats from the three experimental groups were
      subjected to behavioural tests, i.e., constrained swim (despair test) and step
      through passive avoidance response. Animals subjected to prenatal stress showed a
      delayed appearance of all neonatal reflexes and behavioural deficits in
      adulthood, namely increased immobility in the despair test and reduced retention
      of a passive avoidance task. The prenatal treatment with diazepam totally
      counteracted the effect of stress, normalizing the time-course of neonatal
      reflexes and the behavioural responses in adulthood. No difference was seen
      between the effects of the two drug doses. It is concluded that prenatal physical
      stress may induce body growth retardation and may be considered as a model for
      human intrauterine growth retardation. The treatment with an anxiolytic
      benzodiazepine, such as diazepam, may counteract the effects of prenatal stress
      interfering with the biological consequences of stress concerning probably
      cerebral neurotransmitters in both the unborn foetus and the pregnant rat.

PMID- 10208295
TI  - MAO inhibitors and oxidant stress in aging brain tissue.
AB  - The process of aging presents itself with various alterations in physiological
      events. Among many theories, the free radical (FR) theory of aging which reflects
      the FR damage to cellular components is accepted as one of the most important
      theories. Recently, the increases in catecholamine metabolism in aging have also
      attracted attention, and monoamine oxidase (MAO), a key enzyme in this process
      has been extensively studied. The aim of this study was to assess the role of FR
      species via MAO, a possible source of FRs, in physiological aging by determining
      the lipid peroxidation products (LPP) (malondialdehyde, diene conjugates) and
      antioxidant enzyme levels (superoxide dismutase (SOD) and catalase (CAT) in young
      (3 months old, n=10) and aging (16-18 months old, n=10) rat brain tissues of
      Swiss male albino rats. In the second part of the study, the same parameters were
      determined after the acute administration of MAO inhibitors (deprenyl and
      pargyline, 25 mg/kg i.p.) to investigate whether these agents have any beneficial
      effects in reducing oxidant stress via inhibition of MAO. In old rat brains, MAO
      activities showed a significant increase (P=0.000) in addition to an
      insignificant increase in LPP, while SOD (P=0.007) and CAT activities showed a
      decrease with advancing age. After the acute administration of both deprenyl and
      pargyline, a significant decrease in the MAO activities of both young (P=0.0002
      for each) and aging rats (P=0.0002 for deprenyl and P=0.0001 for pargyline) were
      observed. It was noted that deprenyl causes a significant increase in CAT
      activity (P<0.05) but a significant decrease in SOD activity (P<0.05) in young
      rats, while it causes only a significant increase in SOD activity in aging rats
      (P<0.05). Both deprenyl and pargyline cause a significant decrease in conjugated
      diene levels of aging rats (P<0.05). These results confirm the role of
      catecholamine oxidation and MAO activity as one of the causative factors in
      increased oxidant stress during aging. By reducing the oxidant stress observed in
      aging brain, MAO inhibitors, especially deprenyl, may contribute to the control
      of the aging process.

PMID- 10208296
TI  - Distribution of clozapine and desmethylclozapine between blood and brain in rats.
AB  - Desmethylclozapine is the major metabolite of clozapine in serum. Although the
      metabolite is pharmacologically active in vitro, the occurrence of
      desmethylclozapine in brain under steady-state conditions and its role for
      clinical actions of clozapine are unclear. In this study 20 male Sprague-Dawley
      rats received five oral doses of clozapine 20 mg/kg at 1.5-h intervals. At 0.5,
      1, 2 and 5 h after the last administration, at a time four animals were killed
      for analysis of clozapine and desmethylclozapine concentrations in serum and
      brain. The treatment yielded steady-state serum concentrations of clozapine that
      are considered as therapeutically effective in man. Desmethylclozapine
      concentrations exceeded those of clozapine at 2-5 h after drug application. In
      brain, drug concentrations were 15.8-fold higher for clozapine than in serum, but
      only 2.7-fold higher for desmethylclozapine. The brain clozapine concentrations
      exceeded those of desmethylclozapine by about 3 times. These data indicate that
      desmethylclozapine is unlikely to play a role for CNS-mediated effects.

PMID- 10208297
TI  - Gabapentin as monotherapy in the treatment of acute mania.
AB  - Two cases of mania treated with gabapentin, a new anticonvulsant, are presented.
      After 2 weeks of treatment a moderate improvement of both patients was observed.
      The antimanic effect of gabapentin awaits confirmation by systematic, well
      designed studies.

PMID- 10208298
TI  - Is severe depression a separate indication? ECNP Consensus Meeting September 20,
      1996, Amsterdam. European College of Neuropsychopharmacology.
AB  - There is not an accepted definition of severe depression, but using cut-off
      scores on rating scales severe depression is considered to lie at one extreme of
      a continuum of severity. The evidence from epidemiological, biological, and
      clinical efficacy studies does not support severe depression as a separate
      illness category. A good response to antidepressants is seen in both moderate and
      severe depression. The available evidence supports the view that in most cases an
      effective antidepressant in moderate depression is likely to have efficacy in
      severe depression. Few studies have found differences between antidepressants in
      their efficacy in treating severe depression. Most evidence of differential
      efficacy derives from studies of clomipramine, which is perceived as a
      particularly potent antidepressant by many clinicians. Other tricyclic
      antidepressants do not appear to have an advantage in severe depression. Separate
      studies to demonstrate efficacy in severe depression are not necessary for the
      registration of a new antidepressant. However if efficacy in severe depression is
      demonstrated in separate studies this information could be included in the
      summary of product characteristics to provide guidance to clinicians.

PMID- 10208299
TI  - Alternatives to placebo-controlled trials in psychiatry. ECNP Consensus Meeting,
      September 26, 1996, Amsterdam. European College of Neuropsychopharmacology.
AB  - Patients receiving placebo do not merely receive an inert substance but also
      receive support, concern, and reassurance that assists the therapeutic alliance
      and encourages the positive attitude that forms the basis of cognitive treatment.
      Response to non-specific factors is seen in all fields of medicine but is
      particularly potent in psychiatry. The placebo response is variable across
      settings and across time and is unpredictable. Historical data cannot therefore
      provide an adequate control for treatment effects in studies of new drugs. The
      scientific position is clear that a comparison against placebo is required for
      the unequivocal demonstration of the efficacy of a treatment. Evidence from at
      least two positive well designed and conducted placebo-controlled studies is
      generally accepted as appropriate to establish the efficacy of a drug. Attention
      to diagnosis, severity of illness, and to possible comorbid conditions is needed
      in the design and conduct of placebo-controlled studies in order to optimise the
      chance of obtaining valid data. The use of all data obtained, including dropouts
      due to lack of efficacy, should be maximised. The use of placebo may not be
      possible in some conditions that represent medical emergencies or may be
      difficult to justify in serious disorders where an effective treatment has
      already been established. Alternative designs to placebo-controlled studies can
      be considered. Consistent superior efficacy compared with a well accepted,
      effective treatment, given in an easily defended dose, is considered to be good
      evidence of efficacy provided that the studies are well designed and well
      conducted. Evidence of superior efficacy to an established effective comparator
      treatment may be regarded as evidence of efficacy. The demonstration of a dose
      response relationship where one dose is found to be significantly better than
      another, can be taken as evidence for efficacy, particularly where there is
      already placebo-controlled evidence of the efficacy of the identified dose. Where
      a new treatment is found, under controlled conditions, to be equivalent to an
      existing well accepted comparator treatment, given at a clearly effective dose,
      this may be taken as evidence of efficacy, but only if the comparator is
      consistently superior to placebo and if equivalence has been defined beforehand.
      The claims for efficacy based on results from equivalence studies are less easily
      sustained than the evidence from placebo-controlled studies or studies
      demonstrating superior efficacy, due to the fact that those studies have no
      internal validation.

PMID- 10208300
TI  - The failure of placebo-controlled studies. ECNP Consensus Meeting, September 13,
      1997, Vienna. European College of Neuropsychopharmacology.
AB  - In recent years an increasing number of clinical trials to test the efficacy of
      new potential treatments have failed to demonstrate a difference from placebo for
      either the new treatment or for an established reference drug. A rise in the
      response rate to placebo observed in a range of psychiatric disorders has not
      been paralleled by a rise in the response to drug and small effect sizes make it
      difficult to establish significant differences. A number of factors are thought
      to contribute to the rising placebo response or the smaller effect sizes. These
      include differences over time in the populations studied, changes in investigator
      behaviour, and failures of trial design. The inclusion of a greater number of
      patients with mild disorder or whose disorder has a fluctuating course is thought
      likely to increase the placebo response rates. Close attention needs to be paid
      to patient selection in terms of diagnosis, severity and absence of confounding
      comorbidity such as alcoholism, personality disorders or brief depression. The
      rising placebo response is associated with an increasing variability of placebo
      response seen in some centres. The ability of some centres to select appropriate
      patients for studies to demonstrate a separation of reference treatment and
      placebo and the inability of other centres suggests that a more careful selection
      of investigators is important. Selection should be based on their experience,
      their record from previous studies, and their aptitude for being trained. The
      inclusion of a reference treatment arm provides a useful means to judge the
      performance of individual centres. The exclusion of eccentric centres that fail
      to reach predetermined performance criteria, such as a failure to separate
      reference treatment from placebo, may be considered. Trial designs need to
      qualify adequately the study population and pay sufficient attention to
      diagnosis, minimum severity and comorbidity at entry. Greater care is needed in
      excluding concomitant overt or covert psychotherapy and in reducing the
      unnecessary therapeutic contact that has been increased unwittingly by some
      protocols. Identifying patients with prior stability of illness, with clear
      disability, and with a minimum severity at entry is likely to lower the placebo
      response substantially and increase the effect size and power of the study. The
      possible influence of comedication should also be considered. The inclusion of a
      placebo run in period is considered unhelpful and the use of better statistical
      techniques should be adopted to maximise the sensitivity of the study and
      increase the chances of testing efficacy.

PMID- 10208301
TI  - Glucocorticoids increase bradykinin B2 receptor gene transcription in cultured
      guinea-pig tracheal smooth muscle cells.
AB  - We investigated the effect of the glucocorticoid methylprednisolone on the
      modulation of the expression of the bradykinin B2 receptors in cultured, guinea
      pig, tracheal, smooth muscle cells. These receptors are implicated in the
      pathogenesis of human asthma. Untreated cells expressed a single population of
      binding sites for [3H]bradykinin with a dissociation constant, Kd, of 87.7+/-12.0
      pM and a maximum binding site density, Bmax, of 245.4+/-71 fmol/mg protein.
      Treatment of the cultured guinea-pig tracheal smooth muscle cells with
      methylprednisolone 10(-5) M for 6 h increased the number of bradykinin receptors;
      this response reached a maximum of 78% and returned to the basal value after 12
      h. Bradykinin (10(-12) M) elicited a six-fold higher calcium level in treated
      cells than in control cells. To investigate bradykinin B2 receptor mRNA
      expression in guinea-pig cells, we used the reverse transcription polymerase
      chain reaction (RT-PCR) technique to synthesize a specific bradykinin B2 cDNA
      probe of 296 bp corresponding to nucleotides 456-751 of the human sequence. This
      guinea-pig cDNA had 88%, 86% and 83% homology with the corresponding human, mouse
      and rat sequences, respectively, but no homology with any other known sequences.
      Following methylprednisolone treatment, Northern blot hybridization indicated
      that mRNA increased fourfold after 3 h compared with control cells, and returned
      to basal level within 7 h. The rate of gene transcription, assessed by nuclear
      run-on assays, increased fourfold after 3 h treatment with 10(-5) M
      methylprednisolone. These results indicate that glucocorticoids induce early up
      regulation of bradykinin B2 receptors in cultured guinea-pig tracheal smooth
      muscle cells by increasing the rate of transcription of the bradykinin B2
      receptor gene.

PMID- 10208302
TI  - Characterization of nociceptin receptors in the periphery: in vitro and in vivo
      studies.
AB  - Nociceptin (NC), a series of NC fragments, naloxone as well as the pseudopeptide
      [Phe1psi(CH2-NH)Gly2]NC(1-13)NH2 ([F/G]NC(1-13)NH2) were used to characterize NC
      receptors in peripheral isolated organs and in vivo. Experiments on isolated
      organs were performed in the mouse (mVD) and rat (rVD) vas deferens
      (noradrenergic nerve terminals), in the guinea pig ileum (gpI; cholinergic
      nerves) and in the renal pelvis (gpRP; sensory nerves), and, in vivo, by
      measuring the blood pressure (BP) and heart rate (HR) in anaesthetised rats. NC,
      NCNH2 and NC(1-13)NH2 acted as full agonists with similar affinities, while
      shorter fragments (e.g. NC(1-12)NH2, NC(1-9)NH2, NC(1-5)NH2) were much weaker or
      inactive. The inhibitory effects of NC were not modified by naloxone. [F/G]NC(1
      13)NH2 acted as an antagonist with similar pA2-values (6.75 mVD, 6.83 rVD, 7.26
      gpI) in the three species. In addition, it blocked NC actions in the rat in vivo.
      Linear Schild plots with slopes near to unity indicated that [F/G]NC(1-13)NH2 is
      a competitive antagonist, specific for NC receptors both in vitro (since it was
      inactive on opioid receptors) and in vivo (since it was inactive against
      carbachol). [F/G]NC(1-13)NH2 showed a residual agonistic activity in vitro (alpha
      = 0.2-0.3 in the rVD and gpI) and especially in vivo (alpha = 0.4 BP, 0.2 HR).
      These pharmacological data indicate that NC and related peptides exert their
      inhibitory effects in peripheral organs of various species by activating the same
      receptor type. Moreover, [F/G]NC(1-13)NH2 appears to be a useful tool for
      receptor characterization and classification.

PMID- 10208303
TI  - Structure-affinity profile of 8-hydroxycarbostyril-based agonists that dissociate
      slowly from the beta2-adrenoceptor.
AB  - Several carbostyril-based beta-agonists have been shown to bind tightly to and
      slowly dissociate from the beta2-adrenoceptor (beta2AR). In the present study,
      the structural features of 8-hydroxy-5-[2-[(1-phenyl-2-methylprop-2-yl)amino]-1
      hydroxyethyl] -carbostyril (11a) which contribute to its binding properties at
      the beta2AR were investigated using a series of synthesized analogs. The k(off),
      estimated by the rate of cAMP decline in DDT1 MF-2 (DDT) cells with a reduced
      receptor density, Ki and ligand-induced receptor reductions were determined. All
      of the derivatives stimulated cAMP accumulation in DDT cells in the sub to mid
      nanomolar range and elicited the same maximal stimulation as (-)isoproterenol.
      Derivatives of 11a with side chain N-substitutions comprising 2-methylbutyl,
      phenylethyl and isopropyl had higher k(off)-values and lower affinities as
      compared to 11a. Increasing the number of methylenes between the side chain
      tertiary alpha carbon and phenyl from 1 in 11a to 3 or reducing the number to 0
      also resulted in derivatives with higher k(off)- and Ki-values. In addition,
      replacement of the 8-hydroxycarbostyril nucleus of 11a with catechol reduced the
      affinity of the compound for the beta2AR by 48-fold and increased its k(off).
      Only those derivatives with the lowest k(off)-values induced a decrease in the
      receptor density of DDT cell membranes following a preincubation and extensive
      washing. The data show that the 8-hydroxycarbostyril nucleus in conjunction with
      substitutions on the tertiary alpha carbon of the side chain and positioning of
      the phenyl group are important characteristics determining the high affinity and
      slow dissociation of 11a from the beta2AR.

PMID- 10208304
TI  - Effects of antidepressant drugs on the dopamine D2/D3 receptors in the rat brain
      differentiated by agonist and antagonist binding--an autoradiographic analysis.
AB  - In the present study the effect of antidepressant drugs on the density of
      dopamine D2/D3 receptors in the rat forebrain was examined using autoradiography,
      since this technique provides the appropriate anatomical resolution. Male Wistar
      rats were treated with three various antidepressant drugs: imipramine, citalopram
      and mianserin in a dose of 10 mg/kg p.o., acutely (single dose) or repeatedly
      (twice a day for 14 days). To estimate the distribution of D2/D3 receptors, we
      chose following radioligands: [3H]raclopride, a non-selective antagonist of D2/D3
      receptors, and [3H]quinpirole, a non-selective D2/D3 agonist. When [3H]raclopride
      was used as a radioligand, no significant differences in the density of D2/D3
      receptors were observed after administration of the investigated drugs. However,
      following repeated administration of imipramine, citalopram and mianserin, a
      significant increase in the binding of [3H]quinpirole was observed, both in the
      nucleus caudatus and nucleus accumbens septi. In some cases the increase of
      [3H]quinpirole binding was also observed after acute treatment with
      antidepressant drugs. Thus, using an agonist as a radioligand, we were able to
      see upregulation of dopamine D2/D3 receptors in the rat forebrain following
      administration of antidepressant drugs, which might be interpreted as the
      biochemical correlative for the postsynaptic dopamine D2/D3 receptor
      supersensitivity observed in previous behavioral studies.

PMID- 10208305
TI  - Effects of local MAO inhibition in the locus coeruleus on extracellular serotonin
      and 5-HIAA during exposure to sensory and cardiovascular stimuli.
AB  - Previously, we have shown that in the presence of pargyline the release of
      serotonin (5-HT) in the locus coeruleus is modulated by various sensory stimuli
      and blood pressure fluctuations. The aim of the present study was to investigate
      whether local inhibition of monoamine oxidase (MAO) influences basal and stimulus
      induced release of 5-HT in the locus coeruleus. For this purpose, the locus
      coeruleus was superfused in the absence and in the presence of the MAO inhibitor
      pargyline. Additionally, we examined whether the release of the 5-HT metabolite 5
      hydroxy-indole acetic acid (5-HIAA) in the locus coeruleus is altered in response
      to stimuli. The locus coeruleus of the conscious rat was superfused through a
      push-pull cannula with artificial cerebrospinal fluid (CSF). 5-HT and 5-HIAA were
      determined in the superfusate. The basal release rate of 5-HT and the basal
      outflow of 5-HIAA averaged 2.0 fmol/min and 69 fmol/min, respectively. The basal
      release rate of 5-HT and the 5-HIAA outflow were tetrodotoxin (TTX)-sensitive. In
      the absence of pargyline, the sensory stimuli noise stress or tail pinch, applied
      for 10 min, increased 5-HT and 5-HIAA outflow by 50-70%. In contrast, an
      experimentally induced rise in blood pressure for 10 min enhanced 5-HT release by
      50%, but had no effect on 5-HIAA outflow. The release of 5-HT and/or 5-HIAA
      elicited by sensory stimuli or a blood pressure rise was abolished by TTX.
      Addition of pargyline to the CSF enhanced 5-HT release fourfold and slightly
      decreased 5-HIAA outflow. These levels remained stable throughout the entire
      observation period of 8 h. In the presence of pargyline, 5-HT release elicited by
      noise, tail pinch and increase in blood pressure was enhanced. It is concluded
      that superfusion with pargyline enhances 5-HT release and reduces 5-HIAA outflow
      in the locus coeruleus. Furthermore, the ability of sensory stimuli and
      baroreceptor activation to enhance 5-HT release is preserved during a prolonged
      pargyline-induced increase in extracellular 5-HT. Since sensory stimuli enhanced,
      while baroreceptor activation did not influence 5-HIAA outflow, 5-HIAA is not a
      reliable index for short-term changes in the activity of serotonergic neurons in
      the locus coeruleus.

PMID- 10208306
TI  - Comparison of the effects of acute and subchronic administration of atipamezole
      on reaction to novelty and active avoidance learning in rats.
AB  - The effects of an alpha2-adrenoceptor antagonist, atipamezole, on exploratory
      behaviour in a novel environment, spontaneous motor activity and active avoidance
      learning were studied after acute injection and continuous infusion (0.1 mg/kg h)
      for 24 h and 6-9 days in rats. The effects of atipamezole on biogenic amines and
      their main metabolites in brain were studied after an acute injection (0.3 mg/kg
      s.c.) and continuous infusion (0.1 mg/kg h) for 24 h and 10 days. The level of
      central alpha2-adrenoceptor antagonism and the drug concentration in blood and in
      the brain were measured after continuous infusion for 24 h and 10 days. In
      behavioural tests, atipamezole had no effect on spontaneous motor activity at any
      of the doses studied. However, after both acute administration and continuous 24
      h infusion, atipamezole decreased exploratory behaviour in a staircase test, but
      no longer after 6 days of continuous infusion. Acute administration of
      atipamezole impaired performance in active avoidance learning tests causing a
      learned helplessness-like behaviour. When the training was started after 7 days
      of continuous infusion, atipamezole significantly improved active avoidance
      learning. There was a significant increase in the metabolite of noradrenaline
      (NA), 3-methoxy-4-hydroxyphenylethyleneglycol sulphate (MHPG-SO4), after 24 h but
      not any longer after 10 days of continuous atipamezole infusion, although the
      extent of central alpha2-adrenoceptor antagonism was unchanged and the
      atipamezole concentration present in brain was even elevated at 10 days compared
      to levels after 24-h infusion. In conclusion, these results reveal that acute and
      subchronic atipamezole treatments have different and even opposite effects on
      behaviour in novel, stressful situations. After acute treatment, atipamezole
      potentiates reaction to novelty and stress, causing a decrease in exploratory
      activity and impairment in shock avoidance learning. After subchronic treatment,
      there was no longer any effect on exploratory behaviour and, in fact, there was
      an improvement in the learning of a mildly stressful active avoidance test. The
      changes in behaviour occurred in parallel with attenuation in the MHPG-SO4
      increasing effect, thus the suppressed behaviour in the present test conditions
      after acute atipamezole injection is associated with a major increase in central
      NA release. The results support the role of alpha2-adrenoceptors and
      noradrenergic system in reactions both to novelty and stress and have possible
      implications in cognitive functions as well as in depression.

PMID- 10208307
TI  - Atrial fibrillation after coronary artery bypass surgery: association with
      changes in G protein levels in mononuclear leukocytes.
AB  - Atrial fibrillation (AFib) is a frequent complication of coronary artery bypass
      grafting (CABG). Its cause, however, is unknown. As the adrenergic system is
      involved in some types of AFib, we hypothesized that a change in guanine
      nucleotide-binding protein (G protein) expression plays a role in the development
      of post-CABG AFib. In 28 patients undergoing CABG surgery, the G(s alpha)/G(i
      alpha) ratio (stimulatory/inhibitory G protein alpha) at the protein (Western
      blotting) and mRNA (reverse transcription polymerase chain reaction) levels was
      measured before and after surgery. As a suitable test system allowing multiple
      analysis mononuclear leukocytes (MNL) were chosen. The perioperative change of
      the G(s alpha)/G(i alpha) ratio of protein and mRNA was significantly different
      in patients who subsequently developed AFib (eight patients) and in patients who
      did not (20 patients; P<0.01 and <0.001, respectively). On average, the protein
      G(s alpha)/G(i alpha) ratio decreased from 1.79+/-1.13 (mean+/-SD) to 1.32+/-0.69
      in patients without AFib (P=0.1, n.s.) whereas a significant increase from 0.86+/
      0.44 to 1.62+/-0.65 (P<0.01) was observed in patients subsequently developing
      AFib. The mRNA G(s alpha)/G(i alpha) ratio decreased significantly from 0.53+/
      0.24 to 0.36+/-0.11 in patients without AFib (P<0.01) whereas a significant
      increase from 0.31+/-0.14 to 0.47+/-0.13 was observed in those who subsequently
      developed AFib (P<0.05). These results indicate that an increase of the G(s
      alpha)/G(i alpha) ratio in MNL is associated with AFib after CABG surgery and
      possibly may be used as a prognostic indicator of this complication.

PMID- 10208308
TI  - Inhibitory effects of the class III antiarrhythmic drug amiodarone on cloned HERG
      potassium channels.
AB  - The human ether-a-go-go-related gene (HERG) encodes a K+ channel with biophysical
      properties nearly identical to the rapid component of the cardiac-delayed
      rectifier K+ current (I(Kr)). HERG channels are one primary target for the
      pharmacological management of arrhythmias. In this study, we investigated the
      acute effects of the class III antiarrhythmic drug amiodarone on HERG channels
      expressed heterologously in Xenopus oocytes by use of the two-microelectrode
      voltage clamp technique. Amiodarone blocked HERG channels with an IC50 of 9.8
      microM with a maximum outward tail current reduction of 62.8%. The block
      consisted of two main components, a closed channel block that could not be
      reversed within the time of experiments and an open channel block with a slow
      unblock, having a recovery time constant of 73 s at -80 mV. Inactivation of the
      HERG channel at very positive potentials could not prevent amiodarone block.
      These results indicate that HERG channels can be blocked by amiodarone in closed,
      open and inactivated states. The block of open channels was cumulative, use
      dependent and voltage-dependent. In summary, our data suggest that the strong
      class III antiarrhythmic action of amiodarone is at least partially based upon
      its acute inhibitory effects on HERG potassium channels.

PMID- 10208309
TI  - The inflammatory reaction induced by formalin in the rat paw.
AB  - The involvement of bradykinin and some other inflammatory mediators in formalin
      induced oedema and plasma extravasation was examined. Formalin was injected in
      rat paws at two doses, 1.75% or 5%. The lower dose induced the development of an
      immediate oedema associated with a progressive accumulation of 125I-labelled
      albumin in the paws. These changes were suppressed by pretreatment with capsaicin
      or xylocaine. They were abolished by RP67580, a NK1 receptor antagonist, and
      increased by phosphoramidon or diprotin A. They were not affected by HOE140, a
      bradykinin B2 antagonist, captopril, methysergide, mepyramine, indomethacin,
      ketoprofen or L-N(G)-nitroarginine. The higher dose of formalin induced a
      swelling of the paws which took place in two phases associated with two periods
      of increase in vascular permeability. This oedema was reduced by pretreatment
      with capsaicin but not with xylocaine. It was reduced by RP67580 injected before
      or 30 min after formalin. It was inhibited by mepyramine, methysergide,
      indomethacin and NS-398, a cyclooxygenase-2 inhibitor. It was not modified by
      HOE140. Its development was similar in normal and kininogen-deficient rats. We
      concluded that formalin administered at a low dose induces an oedema which mainly
      results from a neurogenic inflammation mediated by neuropeptides such as
      substance P. At higher doses, formalin induces an oedema which mainly depends on
      the release of substance P, prostanoids, 5-hydroxytryptamine and histamine.
      Bradykinin plays no significant role in the vascular changes whereas this peptide
      has been reported to participate in the stimulation of nociceptive afferent
      neurons. This discrepancy could be explained by a difference in the threshold of
      stimulation of the nociceptive neurons and that of the cells of the vascular
      walls, or by a formation of kinins in close contact of the neurons.

PMID- 10208310
TI  - Suppressive effect of pentoxifylline on natural killer cell activity;
      experimental and clinical studies.
AB  - The methylxanthine derivative pentoxifylline, widely used in the treatment of
      vascular diseases, also has numerous immunological effects. In in vitro
      experiments, the human natural killer cell cytotoxicity was investigated in the
      presence of pentoxifylline. A clinical trial involved an investigation of the
      natural killer cell activity in patients to whom pentoxifylline had been
      administered for different periods. The natural cytotoxicity in macroangiopathic
      patients treated with pentoxifylline was compared with that in healthy controls
      and that in patients with vascular diseases who did not receive pentoxifylline
      therapy. A total of 62 macroangiopathic patients and 20 healthy controls were
      investigated. The natural killer cell activity in patients receiving
      pentoxifylline therapy for more than a year proved to be significantly lower
      (P<0.005). The presence of vascular disease did not influence the natural killer
      activity. In the in vitro cytotoxicity reaction, pentoxifylline at a
      concentration of 100 microg/ml was found to suppress the natural killer cell
      cytotoxicity at any stage of the reaction. The influence of pentoxifylline on the
      natural killer cell activity was not due to inhibition of the expression of
      intercellular adhesion molecule-1. However, this drug significantly decreases
      (P<0.05) the apoptosis of target cells. It is presumed that the suppressor effect
      of pentoxifylline on natural killer cell activity should be taken into
      consideration in the treatment of clinical diseases where this drug is
      administered chronically.

PMID- 10208311
TI  - Heterogeneous characteristics of imidazoline-induced insulin secretion.
AB  - Imidazolines are regarded as a pharmacological group of insulin secretagogues
      with one uniform mechanism of action, namely closure of ATP-dependent K+ channels
      (K(ATP) channels) and, in consequence, depolarization of the plasma membrane,
      Ca2+ influx and stimulation of secretion. This assumption was investigated by
      measuring insulin secretion from perifused pancreatic islets in response to three
      imidazoline compounds and comparing the characteristics of secretion with changes
      in membrane potential and cytosolic Ca2+ concentration [Ca2+]i of single beta
      cells. Phentolamine (32 microM) stimulated insulin secretion from perifused mouse
      islets in the presence of stimulatory (10 mM and 30 mM) and substimulatory (5 mM)
      glucose concentrations and even in the absence of glucose. Idazoxan in
      concentrations up to 500 microM was virtually ineffective in the presence of 5 mM
      glucose. At 10 mM glucose, there was a moderate but significant increase of
      secretion by idazoxan, 20 microM being nearly as effective as 100 microM. The
      effect of phentolamine was of slow onset and irreversible in the time frame of
      the experiments, while the effect of idazoxan was of fast onset and reversible.
      Alinidine also stimulated secretion in the presence of 10 mM glucose with fast
      and reversible kinetics, but in contrast to idazoxan, 100 microM was clearly more
      effective than 20 microM. These heterogeneous characteristics of secretion were
      reflected by changes of [Ca2+]i: the increase of [Ca2+]i by phentolamine was slow
      and only partially reversible, whereas idazoxan led to a smaller, but faster and
      reversible response. The increase of [Ca2+]i by phentolamine and idazoxan was
      abolished by the Ca2+ channel blocker D 600. Surprisingly, all three compounds
      depolarized the beta-cell plasma membrane from a resting potential of -71 mV to
      about -36 mV. Again, the effect of phentolamine was slow and that of idazoxan and
      alinidine fast. Thus, the characteristics of phentolamine-induced secretion
      appear to be attributable to the consequences of K(ATP) channel closure. It is
      unclear, however, why all three test compounds achieved the same degree of
      depolarization in spite of their known different efficiency to close K(ATP)
      channels. Apparently, there are additional mechanisms involved in the action of
      idazoxan and alinidine, which may contribute to the obvious differences in the
      characteristics of secretion.

PMID- 10208312
TI  - Involvement of capsaicin-sensitive sensory nerves in early and delayed
      cardioprotection induced by a brief ischaemia of the small intestine.
AB  - Early cardioprotection can be achieved by a brief ischaemia of noncardiac
      tissues. Our study examined whether a brief ischaemia of the small intestine
      induces both early and delayed cardioprotection in the rabbit and assessed the
      possible mechanism involved in the activation of capsaicin-sensitive sensory
      nerves. The plasma concentration of creatine kinase (CK) and infarct size
      (necrotic zone/left ventricular zone) after 30 min coronary artery occlusion and
      180 min reperfusion were determined in rabbits. Infarct size was 35.5+/-6.8% in
      the control non-preconditioned group. Preconditioning induced by a brief period
      of 10-min small intestine ischaemia significantly reduced infarct size (6.5+/
      1.9%, P<0.01 vs. the control non-preconditioned group) and decreased CK release
      (3092+/-236 and 1094+/-117 U/l for myocardial ischaemia-reperfusion and
      preconditioning plus myocardial ischemia-reperfusion, respectively, P<0.01), and
      the protection was partly abolished by pretreatment with capsaicin (50 mg/kg,
      s.c.) 4 days before the experiments. A brief period of anterior mesenteric artery
      occlusion caused an increase in the plasma level of calcitonin gene-related
      peptide-like immunoreactivity (CGRP-LI), an effect which was abolished by
      pretreatment with capsaicin. Similar protection was shown in the animals
      subjected to a brief period of anterior mesenteric artery occlusion 24 h before
      coronary artery occlusion, and this delayed protection was also abolished partly
      by pretreatment with capsaicin. Capsaicin treatment (50 mg/kg, s.c.) alone also
      protected the ischaemic myocardium. The results suggest that brief ischaemia of
      the small intestine induces both early and delayed protection against reperfusion
      induced myocardial injury, and the effects are, at least partly, related to the
      activation of capsaicin-sensitive sensory nerves.

PMID- 10208313
TI  - Intracranial self-stimulation under a progressive-ratio schedule in rats: effects
      of strength of stimulation, d-amphetamine, 7-OH-DPAT and haloperidol.
AB  - Progressive-ratio (PR) schedules, which have been widely used to study the
      reinforcing efficacy of various reinforcers (in particular IV psychostimulants),
      have been very seldom applied to the study of positively reinforcing electrical
      brain stimulation (EBS). In the present study, rats were required to emit a
      progressively increasing number of lever-presses (3,4,6,7,9,11,14,16, etc.) for
      access to successive reinforcers (periods of VTA self-stimulation). Each period
      of self-stimulation consisted of ten trains of square pulses of EBS; each train
      was available under a continuous reinforcement schedule. The number of periods of
      EBS earned during a session was deemed the breaking point (BP). After acquisition
      and stabilization of self-stimulation, a study was carried out to verify that
      changes in the strength of the EBS (i.e. changes in the frequency, the intensity
      or the pulse duration, one parameter at a time) induced changes in the BP. The
      effects of IP pretreatments with d-amphetamine, the dopamine D3/D2 receptor
      agonist 7-OH-DPAT and haloperidol were then assessed. Decreases in the strength
      of EBS decreased the BP. However, increasing the strength above training values
      resulted in minimal increases in the BP. d-Amphetamine (0.25-1 mg/kg) dose
      dependently increased the BP; additionally, when the reinforcer was withheld
      (i.e. in conditions of extinction, with the stimulator turned off) d-amphetamine
      was also found to augment the BP. This might indicate that d-amphetamine
      preferentially potentiated the motivational (non-rewarded presses) aspects of VTA
      self-stimulation under this type of PR schedule. 7-OH-DPAT had biphasic effects:
      at low doses (0.01 and 0.03 mg/kg), it tended to decrease the BP while higher
      doses (1 and 3 mg/kg) robustly increased the BP. Under conditions of extinction,
      7-OH-DPAT (1 mg/kg) had a tendency to increase the BP, but this effect was not
      statistically significant and did not approach the magnitude of effects observed
      with d-amphetamine. Haloperidol (0.08-0.48 mg/kg IP) dose-dependently reduced the
      BP, suggestive of a decrease in the reinforcing efficacy of the EBS. These
      results show that rats can be trained to self-administer EBS of the VTA under a
      PR schedule of reinforcement and that this behaviour is sensitive to disruption
      or potentiation of dopaminergic neurotransmission.

PMID- 10208314
TI  - Effects of synthetic delta9-tetrahydrocannabinol on binocular depth inversion of
      natural and artificial objects in man.
AB  - Binocular depth inversion represents an illusion of visual perception that is
      sensitive to various behavioural and psychiatric conditions. It is affected by
      cannabinoids, reflecting associated changes in perception. The present study
      investigated the differences in binocular depth inversion of different classes of
      natural and artificial objects and the effect of synthetic delta9
      tetrahydrocannabinol (Dronabinol) on these illusionary perceptions. Using this
      model, the effects of orally administered Dronabinol on binocular depth inversion
      were investigated in 17 healthy male volunteers. Pictures from natural and
      artificial objects were presented stereoscopically and the depth perception of
      the volunteers was scored in an operationalized way. The timecourse of the
      effects of Dronabinol on binocular depth inversion was analyzed with regard to
      the stimulus classes (natural and synthetic objects). Significant differences in
      binocular depth inversion of the different groups of stimuli were revealed.
      Objects with a higher degree of everyday familiarity were generally seen as more
      illusionary than those with a lower degree of everyday familiarity. A strong
      impairment of binocular depth inversion due to Dronabinol was found in most
      classes of objects. Analysis of different stimulus classes provides further
      information on the underlying perceptual processing of binocular depth inversion.
      An impairment of top-down processing of visual sensory data by Dronabinol is
      suggested. The anandamidergic system seems to be involved in areas of visual
      information processing.

PMID- 10208315
TI  - Dose-dependent stereoselective activation of the trigeminal sensory system by
      nicotine in man.
AB  - RATIONALE: Nicotine applied to the nasal cavity can evoke 'odorous' sensations in
      the concentration range near the detection threshold by the activation of the
      olfactory sensory system and at higher concentrations 'burning' and 'stinging'
      sensations by the dose-dependent recruitment of C- and Adelta-fibers of the
      trigeminal sensory system. Neuronal nicotinic acetylcholine receptor (nAchR)
      subunits are expressed in trigeminal primary afferents and could constitute the
      receptors involved in nicotine perception. OBJECTIVE: In the present study, we
      dose-dependently investigated the stereoselective effects of R(+)- and S(-)
      nicotine on the trigeminal and olfactory sensory system in man. METHODS:
      Trigeminal detection thresholds for the 'burning' and 'stinging' sensations and
      the olfactory detection threshold for the 'odorous' sensation were determined. In
      order to quantify trigeminal activation, we recorded summated electrical
      responses from the respiratory nasal mucosa during stimulation with R(+)-and S(-)
      nicotine vapor (40, 80, 120, 160 ng/ml; stimulus duration: 250 ms). In addition,
      subjects rated the intensity of 'odorous', 'burning' and 'stinging' sensations.
      For chemical stimulation with nicotine enantiomers, a vapor-dilution olfactometer
      (constant flow rate: 140 ml/s, humidity: 80%, temperature: 37 degrees C, stimulus
      duration 250 ms) was employed. RESULTS: We found significant stereoselective
      differences for the trigeminal but not for the olfactory system, i.e. higher
      summated responses, higher trigeminal intensity estimates, and lower trigeminal
      detection thresholds for S(-)- compared to R(+)-nicotine. CONCLUSION: Our results
      clearly demonstrate the different stereoselective activation of the trigeminal
      sensory system by R(+)-and S(-)-nicotine, indicating the presence of specific
      stereoselective receptors on trigeminal nociceptive Adelta- and C-fibers.

PMID- 10208316
TI  - Enhanced morphine- and cocaine-induced behavioral sensitization in alcohol
      preferring AA rats.
AB  - Locomotor stimulation and behavioral sensitization induced by acute and repeated
      treatment with alcohol, cocaine or morphine were studied in the alcohol
      preferring AA (Alko, Alcohol), alcohol-avoiding ANA (Alko, Non-Alcohol) rats and
      non-selected Wistar rats. Daily treatment with alcohol (ethanol, 0.4 or 1.0 g/kg,
      IP) for 6 days had no effect on locomotor activity either in the AA or ANA rats.
      Acute cocaine (5, 10 or 20 mg/kg, IP) produced a locomotor stimulation in the
      animals of all lines studied, and there was no difference in this effect between
      the AA and ANA rats. During a 4-day repeated cocaine treatment, the AA rats
      became sensitized with the 10 mg/kg dose, while the ANA rats did not show any
      sensitization with this dose. With the 20 mg/kg cocaine dose, in addition to
      locomotor stimulation, the rats of all lines studied showed stereotyped behavior,
      which response was enhanced during repeated treatment. Morphine-induced locomotor
      stimulation was larger in the AA rats than in the ANA or Wistar rats both with
      1.0 and 3.0 mg/kg doses and only the AA rats were sensitized during 4-day
      treatment with the 1 mg/kg dose. With the 3.0 mg/kg morphine dose, only the AA
      rats showed a weak sensitization evident only during the initial 30 min after
      morphine injection. As the drug-induced behavioral sensitization is an important
      factor in the development of drug addiction, it is possible that mechanisms
      underlying the enhanced susceptibility of the AA rats to morphine- and cocaine
      induced sensitization contribute to the high intake of alcohol and other abused
      drugs by these animals.

PMID- 10208317
TI  - Effects of sustained cocaine exposure on sensorimotor gating of startle in rats.
AB  - Deficient sensorimotor gating, as measured by a relative loss of prepulse
      inhibition (PPI) of the startle reflex, has been reported in schizophrenia
      patients and in rats treated acutely with dopamine (DA) agonists or other
      psychotomimetic agents. For this reason, PPI has been used as a cross-species
      measure for studying the neurochemistry of specific information processing
      deficits in schizophrenia. Cocaine is a DA reuptake inhibitor which can
      precipitate psychosis after sustained use in humans. In rats, sustained exposure
      to cocaine results in neuropathological and neurochemical changes in several
      brain regions, and is also associated with specific prolonged behavioral
      abnormalities. In the present study, we examined the effects of both acute and
      sustained cocaine administration on PPI and other measures of the startle reflex
      in rats. Cocaine produced a significant, dose-dependent reduction in PPI, both
      after acute administration, and after 3 days of sustained administration via
      implanted subcutaneous pellets. PPI returned to control levels when rats were
      tested 10 days after sustained (5 day) cocaine administration. The effects of
      acute cocaine administration on PPI are consistent with those of other DA
      agonists and psychotomimetics, but PPI does not appear to be sensitive to lasting
      effects of a method of prolonged cocaine administration associated with
      neuropathological and neurochemical changes in several brain regions.

PMID- 10208319
TI  - Effects of repeated ethanol administration in the plus maze; a simple model for
      conditioned abstinence behaviour.
AB  - Classical conditioning is considered to be an important factor in drug
      dependence. Exposure to an environment in which alcohol has been repeatedly
      consumed may produce feelings of anxiety and dysphoria in a currently abstinent
      patient, and may precipitate relapse drinking. The present study modeled this
      process, by repeatedly exposing mice to an elevated plus maze after ethanol
      administration. When ethanol injections and maze exposure were repeated for 9
      days, and the ethanol injections replaced by saline on the tenth day, mice
      consistently exhibited a characteristic behaviour pattern, with increased
      stretched attend postures and proportion of time spent in the central square.
      This behaviour was different from that previously seen during withdrawal from
      ethanol, and was not observed when repeated injections of ethanol were given
      either without, or after, maze exposure. Thus the characteristic behaviour
      pattern appeared to be contingent on the animals being repeatedly exposed to the
      maze environment while under the influence of ethanol. In particular, the
      reduction in stretched attend postures produced by acute ethanol, the tolerance
      to this behaviour seen after repeated ethanol and the increase in it after
      replacement of ethanol by saline, are consistent with the pattern predicted for a
      behavioural response to the absence of ethanol, conditioned to the environment of
      the maze.

PMID- 10208318
TI  - Calcium channel agonist (-)-BAY k 8644 suppresses free and limited access intake
      of alcohol in genetic drinking rats.
AB  - Drugs which possess selective actions on a given voltage operated calcium (Ca2+)
      channel (VOCC) are reportedly involved in the pharmacological actions of alcohol.
      Recently it was shown that the 1,4-dihydropyridine (-)-BAY k 8644, an L-type VOCC
      agonist, reduces alcohol intake relatively selectively in the genetic drinking AA
      rat. This study determined whether (-)-BAY k 8644 would alter volitional alcohol
      drinking in two other genetic models of alcoholism, male P rats and a new strain
      of male and female high ethanol preferring (HEP) rats. By use of a standard 10
      day preference test for water versus 3 to 30% alcohol, the maximally preferred
      concentration of alcohol was first determined for each rat individually, i.e. 9%,
      13% or 15%. Then the rats were allowed free access over 24 h or limited access to
      alcohol for only 2 h, during which time the intakes of water and preferred
      solution of alcohol were recorded. After the drinking patterns stabilized for 4
      days, saline, a solutol vehicle solution or (-)-BAY k 8644 was administered: (1)
      in a dose of 0.125, 0.25 or 0.5 mg/kg given intraperitoneally twice daily for 4
      days during free access to alcohol; and (2) for 3 days in a dose of 0.125 or 0.25
      mg/kg given subcutaneously 30 min prior to 2 h of limited access to alcohol.
      Fluid intakes were recorded for either 4 or 8 days after limited and free access
      conditions, respectively. Whereas the control solutions were without effect
      during 24 h access, (-)-BAY k 8644 caused a significant dose-dependent
      suppression of up to 80% in absolute g/kg and proportion of alcohol to total
      fluid consumed; this decline persisted in the post drug period. During the
      limited access paradigm, (-)-BAY k 8644 similarly reduced alcohol drinking
      maximally within the first 15 min of presentation of alcohol; again, this
      reduction persisted over the remaining 105 min of alcohol access. Also,
      individual levels of blood alcohol declined concurrently with the suppression of
      drinking. These results demonstrate that (-)-BAY k 8644 possesses a short latency
      of action on alcohol intake and that its salutary effects on drinking persist
      after the drug is terminated. Finally, the hypothesis that L-type calcium channel
      agonists may be useful as a therapeutic adjunct in the treatment of alcoholism is
      extended.

PMID- 10208320
TI  - Task-dependent effects of the antidepressant/antipanic drug phenelzine on memory.
AB  - Phenelzine (PLZ) is a non-selective monoamine oxidase (MAO) inhibitor commonly
      used to treat depression and panic disorder. In addition to increasing levels of
      biogenic amines in the brain, PLZ elevates brain levels of the amino acid gamma
      aminobutyric acid (GABA; Baker et al. 1991; present study). Given the extensive
      evidence implicating biogenic amines and GABA in mnemonic processes, PLZ may
      affect learning and memory. To investigate this possibility, male Sprague-Dawley
      rats were given PLZ sulfate (15 or 30 mg/kg, based on free base weight) 2 h prior
      to training in a continuous multiple trial inhibitory avoidance (CMIA) and
      spatial water maze task. Retention was assessed 48 h later. The results indicated
      that PLZ enhanced CMIA and impaired water maze retention performance. Compared to
      control rats, rats given PLZ took significantly longer to re-enter the shock
      compartment and swam longer distances before reaching the escape platform on the
      retention tests. These effects of PLZ did not appear to be the result of PLZ
      induced changes in acquisition or retrieval processes, activity levels, or
      footshock sensitivity. Combined, these findings indicate that PLZ influences
      memory in a task-dependent manner. These differential effects of PLZ may be the
      result of contrasting influences of GABA and biogenic amines on memory.

PMID- 10208321
TI  - The relationship of the platelet 5-HT-induced calcium response to clinical
      symptoms in eating disorders.
AB  - Clinical observations indicate that persons with eating disorders exhibit many
      psychopathologic symptoms such as difficulty with impulse control and depressed
      mood associated with impaired regulation of serotonin (5-HT) synaptic function in
      the central nervous system. In this study, we focused on the relationship between
      the 5-HT-induced calcium response in platelets and the clinical symptoms. While
      age, body weight, and severity of depressive symptoms were not correlated with 5
      HT-induced response, there was an enhanced response in patients with bulimic
      symptoms or other impulsive behaviors. Moreover, patients with multi-impulsive
      behaviors had a significantly higher maximal increase than patients with uni
      impulsive behavior, i.e., those who had only bulimic symptoms, as well as non
      impulsive patients, and controls. Considering these results, the 5-HT-induced
      response may be related to difficulty with impulse control in general rather than
      bulimic eating attitudes specifically.

PMID- 10208322
TI  - Specific attentional dysfunction in adults following early start of cannabis use.
AB  - RATIONALE AND OBJECTIVE: The present study tested the hypothesis that chronic
      interference by cannabis with endogenous cannabinoid systems during peripubertal
      development causes specific and persistent brain alterations in humans. As an
      index of cannabinoid action, visual scanning, along with other attentional
      functions, was chosen. Visual scanning undergoes a major maturation process
      around age 12-15 years and, in addition, the visual system is known to react
      specifically and sensitively to cannabinoids. METHODS: From 250 individuals
      consuming cannabis regularly, 99 healthy pure cannabis users were selected. They
      were free of any other past or present drug abuse, or history of neuropsychiatric
      disease. After an interview, physical examination, analysis of routine laboratory
      parameters, plasma/urine analyses for drugs, and MMPI testing, users and
      respective controls were subjected to a computer-assisted attention test battery
      comprising visual scanning, alertness, divided attention, flexibility, and
      working memory. RESULTS: Of the potential predictors of test performance within
      the user group, including present age, age of onset of cannabis use, degree of
      acute intoxication (THC+THCOH plasma levels), and cumulative toxicity (estimated
      total life dose), an early age of onset turned out to be the only predictor,
      predicting impaired reaction times exclusively in visual scanning. Early-onset
      users (onset before age 16; n = 48) showed a significant impairment in reaction
      times in this function, whereas late-onset users (onset after age 16; n = 51) did
      not differ from controls (n = 49). CONCLUSIONS: These data suggest that beginning
      cannabis use during early adolescence may lead to enduring effects on specific
      attentional functions in adulthood. Apparently, vulnerable periods during brain
      development exist that are subject to persistent alterations by interfering
      exogenous cannabinoids.

PMID- 10208323
TI  - The motivation for beer in rats: effects of ritanserin, naloxone and SR 141716.
AB  - Rats were given two weeks of home cage access to either "near-beer" (a beverage
      that tastes like beer but contains <0.5% ethanol v/v) or near-beer with added
      ethanol (4.5% v/v), which is simply referred to as "beer". The two groups of rats
      (near-beer and beer) were then trained on a "lick-based progressive ratio
      paradigm" in operant chambers in which an ever increasing number of licks had to
      be emitted for each successive fixed unit of near-beer or beer delivered. Break
      points (the ratio at which responding ceased) for near-beer and beer were
      approximately equal under baseline conditions. Rats were then tested for the
      effects of the 5HT2A/2C receptor antagonist ritanserin (0.625, 2.5 or 10 mg/kg),
      the opioid receptor antagonist naloxone (0.625, 2.5 or 10 mg/kg) or the
      cannabinoid CB1 receptor antagonist SR 141716 (0.3, 1 or 3 mg/kg). All three
      drugs caused a dose-dependent reduction of break-points and locomotor activity in
      both the beer and near-beer groups. However, the effects of SR 141716 and
      naloxone, but not ritanserin, on breakpoints were significantly more pronounced
      on rats drinking beer compared to those drinking near-beer. There were no such
      differential effects of any of the drugs on locomotor activity across the two
      groups. These results suggest that both SR 141716 and naloxone differentially
      affect the motivation to consume alcoholic beverages and may thus have potential
      as drugs for the treatment of alcohol craving.

PMID- 10208324
TI  - Bremazocine reduces unrestricted free-choice ethanol self-administration in rats
      without affecting sucrose preference.
AB  - It has been postulated that opioid systems in the brain may play a role in
      ethanol reinforcement. In this respect, mu- and delta-opioid receptors may
      mediate the rewarding effects whereas kappa receptors are thought to mediate the
      aversive effects of opioids. Accordingly, long-acting benzomorphans such as
      bremazocine, that simultaneously act as mu and delta receptor antagonists and
      kappa receptor agonists may be particularly effective in reducing ethanol self
      administration. Therefore, we studied the effect of bremazocine on oral ethanol
      self-administration in rats using a paradigm [unrestricted free-choice drinking
      of 10% (v/v) ethanol], previously shown to cause long-term neuroadaptations in
      the nucleus accumbens and caudate putamen. Bremazocine (0.1 mg/kg, once daily for
      five consecutive days) reduced ethanol drinking by about 50% during the active
      period of the animals, whereas the intake of sucrose (3-10% w/v) was affected
      neither in naive nor in ethanol-experienced rats. This effect of bremazocine
      appeared not to be secondary to its acute sedative effect or the slight increase
      in total fluid consumption. Unlike bremazocine, the selective kappa-opioid
      receptor agonist U50,488H (10 mg/kg, once daily) inhibited ethanol drinking only
      during the first of 5 treatment days and the opioid receptor antagonist
      naltrexone (0.3-10 mg/kg, once daily) only caused a modest (about 20%)
      suppression of ethanol drinking during the first hours after drug injection.
      Thus, bremazocine appears to be far more potent than the clinically applied drug
      naltrexone in this respect. Our data further support the role of opioid receptors
      in ethanol reinforcement and indicate that long-acting mixed-action opioids such
      as bremazocine may be useful as adjuvants for the clinical management of ethanol
      addiction.

PMID- 10208325
TI  - Differential EEG effects of the anxiolytic drugs, deramciclane (EGIS-3886),
      ritanserin and chlordiazepoxide in rats.
AB  - The influence of serotonergic and benzodiazepine type anxiolytic drugs on the
      cortical activation and sleep-wakefulness cycle were compared by evaluating the
      effects of ritanserin and deramciclane (EGIS-3886), two 5-HT2 receptor
      antagonists, and chlordiazepoxide on the electroencephalogram (EEG) in freely
      moving rats. Following drug administration (1, 3, and 10 mg/kg, PO for all
      drugs), EEG was continuously sampled for 6 h and power spectra were calculated
      for every 5 s to assess changes in slow wave activity and sleep phases. In a
      separate test, anticonvulsant effects of the drugs were examined in mice. Both
      deramciclane and ritanserin slightly increased total time spent in deep sleep
      (DS) and lengthened sleep episodes. In contrast, chlordiazepoxide had a strong
      inhibitory action on DS, sleep time being shifted to more superficial light sleep
      (LS). The incidence and length of the high voltage spindle (HVS) episodes
      characteristic for the motionless, awake rat were increased at the highest dose
      of both deramciclane and ritanserin, while it was decreased by chlordiazepoxide.
      In mice, chlordiazepoxide had a marked anticonvulsant effect, while deramciclane
      was moderately effective and ritanserin ineffective. In conclusion, the 5-HT2
      receptor antagonist anxiolytic drugs seem to be superior compared to the
      benzodiazepine type anxiolytic drug, chlordiazepoxide, as ritanserin and
      deramciclane improved sleep quality by increasing sleep episode length and time
      spent in DS, while chlordiazepoxide enhanced sleep fragmentation and decreased
      DS.

PMID- 10208326
TI  - Weapon location following suicidal gunshot wounds.
AB  - The location of the gun following suicidal gunshot wound was studied by reviewing
      574 such deaths in which the scene was investigated by a medical examiner
      investigator and the body was examined at the Bexar County Medical Examiner's
      Office in San Antonio, Texas. The position of the gun could not be established in
      76 cases. In the remaining 498 cases, the gun remained in the deceased's hand in
      24% of the cases. In 69% of the cases, the gun was on or near the body but not in
      the hand (i.e., touching the body or within 30 cm of the body). The gun was found
      >30 cm from the body in the remaining 7% of cases. In the case of handguns, the
      gun was found in the hand in 25.7% of individuals. For individuals using long
      guns, the firearm was in the hand of the decedent in 19.5% of cases. The gun had
      a greater chance of remaining in the deceased's hand if the person was lying or
      sitting when the gunshot wound was received. Variables such as gender of the
      individual, wound location, and caliber of handgun were not significant in
      predicting whether the gun stayed in the hand after a suicidal gunshot wound.

PMID- 10208327
TI  - Death due to concussion and alcohol.
AB  - We encountered 5 deaths following blunt trauma to the face and head in which the
      injuries were predominantly soft tissue in nature with absence of skull
      fractures, intracranial bleeding, or detectable injury to the brain. All
      individuals were intoxicated, with blood ethanol levels ranging from 0.22 to 0.33
      g/dl. We feel that in these deaths, ethanol augmentation of the effects of
      concussive brain injury, with resultant posttraumatic apnea, was the mechanism of
      death.

PMID- 10208328
TI  - Prolonged activity after an ultimately fatal gunshot wound to the heart: case
      report.
AB  - In this article, we describe an unusual case of suicide involving a gunshot wound
      to the left ventricle. The victim engaged in premortem activity that was both
      prolonged and methodical. This report stresses the importance of a complete
      investigation to distinguish such case from an homicide.

PMID- 10208329
TI  - Entrance, exit, and reentrance of one shot with a shotgun.
AB  - The case being reported is one of a homicidal shotgun fatality with an unusual
      wound pattern. A 34-year-old man was shot at close range with a 12-gauge shotgun
      armed with No. 5 birdshot ammunition. The shot entered the left axillary region,
      exited through the left infraclavicular region, and thereafter penetrated the
      left side of the neck, causing tearing of the left common carotid artery and the
      right internal carotid artery. The entrance wound in the axilla was larger than
      the other wounds, and before autopsy it was believed that the shotgun had been
      fired twice, causing one wound in the neck and one wound perforating the
      infraclavicular region and exiting through the left axillary region. Thus, this
      case shows that unusual wound patterns in shotgun fatalities can easily lead to
      incorrect assumptions with regard to number and direction of shots fired unless
      thorough investigation is carried out postmortem.

PMID- 10208330
TI  - Shaken baby syndrome and the death of Matthew Eappen: a forensic pathologist's
      response.
AB  - Subdural hemorrhage, retinal hemorrhage, and cerebral edema have been considered
      diagnostic for a "shaken infant" since the syndrome was described almost 30 years
      ago. However, the specificity of these findings has been disputed by defense
      witnesses in recent U.S. criminal prosecutions. This review examines the
      scientific basis for the shaken baby syndrome.

PMID- 10208331
TI  - Initiation of formal death investigation procedures among the Northern Plains
      Indians: a necessary adjunct in the study of American Indian sudden infant
      deaths.
AB  - The high rate of infant mortality among native peoples in the Aberdeen Service
      Area of the Indian Health Service (primarily North and South Dakota) prompted a
      multi-institutional study of this problem. The study investigators assumed that
      local coroners or medical examiners would be able to perform suitable death scene
      investigations. However, during the design portion of the study it became
      apparent that, with one exception, none of the participating Indian Nations had a
      death investigator or even a legal mandate to provide death investigation. To
      allow the study to go forward, and ultimately to better the community health
      within its service area, the Aberdeen Area Indian Health Service submitted a
      draft enabling coroner legislation/resolutions to the area tribes. By November of
      1996, 6 of the 19 Indian Nations enacted enabling coroner legislation. To
      facilitate both the study and general death investigation within the area, the
      Aberdeen Area Indian Health Service since 1993 has held five 2-day death
      investigation training programs covering a variety of death investigation topics
      which were attended by 68 participants. Without further recognition of the need
      for tribal death investigation and additional funding, these gains in tribal
      death investigation will probably be transitory.

PMID- 10208332
TI  - Suicide under the age of eighteen: a 10-year retrospective study.
AB  - The number of suicides in the pediatric age group is rising, and death
      investigators need to be aware of the common scenarios, risk factors, and victims
      as they investigate such cases to properly assign the cause and manner of death.
      We reviewed all pediatric cases referred to the Medical University of South
      Carolina, Forensic Section, from January 1988 through January 1998. Thirty-one
      cases of pediatric suicide were analyzed with regards to age, gender, race, cause
      of death, surrounding circumstances, and past history. Sixty-eight percent of
      victims were aged 16 or 17 years, 84% were male, 68% were white, 78% used
      firearms to commit suicide, 81% were found within close vicinity of their home,
      and 26% had a documented history of mental illness. Suicide is a manner of death
      that is often difficult for the public to accept, especially in pediatric cases.
      We report our findings in this 10-year retrospective study to better understand
      this entity and work toward the prevention of future cases.

PMID- 10208333
TI  - Artifactual injuries of the larynx produced by resuscitative intubation.
AB  - Over a period of 9 months we examined a series of 50 deaths due to natural and
      unnatural causes in which there had been endotracheal intubation and chest
      compression during resuscitation at the scene or in the emergency department
      shortly before death. In 37 of 50 cases (74%) there were airway injuries directly
      resulting from the intubation procedure which we documented using a standardized
      protocol and photography. Specific airway injuries, ranging from petechiae to
      contusions, included oral injury (28%), posterior pharyngeal injury (16%),
      epiglottic injury (22%), piriform recess injury (12%), laryngeal and tracheal
      mucosa injury (64%), strap muscle hemorrhage (14%), and cutaneous injury of the
      neck (4%). In addition, we recorded the presence of facial (6%) and conjunctival
      petechiae (21%) and attributed these changes to resuscitative chest compression.
      No cases had associated fractures of the hyoid or thyroid cartilage. Based on our
      findings, we conclude that resuscitative intubation can cause artifactual injury
      that may mimic inflicted injuries caused by neck compression, including
      strangulation and neck holds.

PMID- 10208334
TI  - Sudden death after a cold drink: case report.
AB  - We report a case of sudden cardiac death in a 12-year-old boy after rapid
      ingestion of a frozen slurry drink. The cause of death was determined to be a
      cardiac arrhythmia secondary to a previously undiagnosed cardiac rhabdomyoma with
      associated myocardial scarring. Ingestion of cold liquids has been associated
      with syncope, but not sudden cardiac death. In this case, bradycardia induced by
      cold-induced vasovagal reflex may have precipitated the terminal arrhythmia.
      Ingestion of cold liquids should be considered a potential trigger for fatal
      cardiac arrhythmias in patients with underlying heart disease.

PMID- 10208335
TI  - Exit association-mediated suicide: toxicologic and forensic aspects.
AB  - The Swiss German chapter of the Exit Association provides conditional assistance
      to individuals wishing to end their own lives. The Exit Association advocates
      death with dignity and fights for the right to freely choose the timing of one's
      own death. According to the Swiss criminal code (articles 114 and 115),
      altruistic assistance to suicide is not punishable. Active euthanasia is punished
      by imprisonment. An individual commits active euthanasia if he or she is driven
      by honorable motives (e.g., pity) and causes the death of another person wishing
      to die who seriously and insistently requests such action. Based on our
      information, the preparation for suicide and its completion relies on a well
      defined protocol. First, the candidate's eligibility for Exit Association
      assistance is verified. The candidate then writes a farewell declaration that
      explicitly confirms the will to terminate his or her own life. A written report
      describes the events during the suicide procedure. Depending on the
      circumstances, the investigative judge requests a forensic autopsy and
      toxicologic analyses. The results of the forensic investigations conducted in the
      cases presented here are in agreement with the scenario described in the reports
      of the Exit Association, namely, suicide by massive ingestion of pentobarbital.

PMID- 10208336
TI  - Sudden death in an infant caused by rupture of a basilar artery aneurysm.
AB  - Ruptured aneurysms of the cerebrovasculature in infancy and early childhood,
      except for "giant" aneurysms and arteriovenous malformations, are rare. Seizures,
      loss of consciousness, and apnea are the usual presenting signs in infancy;
      symptoms such as headache or visual disturbances and signs such as cranial nerve
      compression or meningeal irritation commonly found in older children or adults
      are absent in infants. However, the morphologic findings (i.e., subarachnoid and
      retinal hemorrhage, and occasionally subdural hemorrhage) may be mistaken for
      inflicted trauma, especially if the aneurysm is not identified. Sudden death
      caused by rupture of a cerebral aneurysm has not been previously described in an
      infant. This report outlines the investigation and autopsy findings in a 7-month
      old infant who died unexpectedly as a result of rupture of a complex basilar
      artery aneurysm.

PMID- 10208337
TI  - Late-form hemorrhagic disease of the newborn: a fatal case report with
      illustration of investigations that may assist in avoiding the mistaken diagnosis
      of child abuse.
AB  - Hemorrhagic disease of the newborn (HDN) is usually a self-limiting hemorrhagic
      disorder of childhood that occurs as a result of vitamin K deficiency. It may be
      defined as early or late form depending on the time of onset related to birth.
      HDN is recognized as one of several bleeding disorders that can mimic the
      findings of nonaccidental head injury and may lead to a mistaken diagnosis of
      child abuse. We present a single fatal case of late-onset HDN with illustration
      of hematologic assays that can be performed to assist the pathologist in making
      the correct diagnosis of HDN.

PMID- 10208338
TI  - Myocardial sarcoidosis in forensic medicine.
AB  - Sudden death is the most common manifestation of myocardial sarcoidosis, which is
      often clinically silent. The disease is rarely encountered in forensic medicine,
      but the diagnosis is important because it may change the interpretation of the
      manner of death and thus have insurance implications. Six cases of myocardial
      sarcoidosis diagnosed at autopsy are reported, and the significance of the
      findings is discussed.

PMID- 10208339
TI  - Asplenia as a cause of sudden unexpected death in childhood.
AB  - Sudden unexpected death in childhood is rare. The commonest causes of such deaths
      are a result of fulminating infections of the respiratory or nervous systems.
      Other causes include unsuspected congenital abnormalities of the heart, acute
      metabolic disorders, and rarities such as internal hemorrhages and pulmonary
      thrombosis. Recognition of children with congenital asplenia who are otherwise
      normal but have an increased susceptibility to overwhelming sepsis is extremely
      difficult. We reviewed 1763 autopsy files from our institution over 5 years (1990
      1995), of which 293 were classified as pediatric cases. The vast majority of the
      cases were stillbirths and deaths within the first year of life as a result of
      complex congenital anomalies. Four cases of asplenia were identified in our
      entire series, 3 of which were of the congenital syndromal variety and 1 of which
      was a case of isolated sporadic congenital asplenia. All 4 cases of asplenia were
      analyzed in detail with respect to autopsy findings and cause of death. Severe
      complex cardiac malformations were present in the congenital syndromal asplenia
      patients; these other malformations contributed significantly to their death. In
      this report, we discuss in detail the autopsy findings in a previously healthy 4
      year-old girl who presented with a brief 8-hour history of being unwell and died
      within 4 hours of admission into the hospital. She had sporadic, isolated
      congenital asplenia complicated by high-grade type 6B pneumococcemia and acute
      bilateral adrenal hemorrhage (Waterhouse-Friderichsen syndrome). Previously
      healthy children who clinically deteriorate very rapidly should have a blood
      smear done as part of their clinical workup. The detection of Howell-Jolly bodies
      on a peripheral blood smear can be an indicator of asplenia, and this diagnosis
      can be confirmed by medical imaging of the abdomen. Such steps may aid in the
      aggressive management of isolated congenital asplenia and thereby avert untimely
      death.

PMID- 10208340
TI  - Adrenocortical insufficiency.
AB  - Primary adrenocortical insufficiency is a rare disease which may present with
      protean clinical symptoms and signs. At one end of the spectrum is the patient
      with a long clinical history with marked pigmentation and documented episodes of
      crises which may follow relatively minor viral illnesses. The other extreme is
      illustrated by patients with a rapid deterioration in health culminating in
      unexpected or unexplained death. In the latter instances, the forensic
      pathologist may well be involved, and the case will present a significant
      challenge to diagnosis. We report 5 cases of primary and secondary adrenocortical
      insufficiency seen at the Victorian Institute of Forensic Medicine in 1 year. One
      adult man presented as a case of sudden unexplained death. In 2 cases, the
      diagnosis of adrenocortical insufficiency was raised following postmortem
      examination and confirmed by the treating physician following further
      consultation. In the remaining 2 cases, the diagnosis was known prior to
      postmortem examination and the diagnosis confirmed.

PMID- 10208341
TI  - Posttraumatic diaphragmatic hernia and death--etiologic factor or putrefactive
      artifact?
AB  - Late-presenting diaphragmatic hernias, whether congenital or acquired, may remain
      clinically undetected until mediastinal shift with cardiorespiratory compromise
      or intestinal or gastric infarction with perforation occur. A right-sided
      diaphragmatic hernia with herniation of small intestine into the adjacent pleural
      cavity is described in a 72-year-old man who was found dead at home in a
      putrefactive state. Subsequently, a history of a motor vehicle accident 8 years
      previously was obtained. Although postmortem herniation due to extensive
      putrefactive change may have occurred, producing gaseous distention and migration
      of the intestine, tight twisting of the herniated intestine several times around
      a pleural fibrous adhesion suggested that the herniation could have been an
      antemortem event. Unfortunately, marked tissue autolysis prevented assessment of
      possible ischemic changes in the herniated intestine. Although diaphragmatic
      hernia may be a contributing factor to death at all ages, it may not be possible
      to exclude it as an artifact of putrefaction in a predisposed individual.

PMID- 10208342
TI  - Diffuse axonal injury in a rugby player.
AB  - Sections of the cerebrum, cerebellum, and brain stem of a rugby player who died
      15 hours after being tackled were stained using an immunoperoxidase technique to
      detect beta-amyloid protein. The sections of the pons showed axonal spheroids in
      the base, and those of the cerebellum showed axonal spheroids in deep white
      matter. The findings demonstrated axonal injury following a fall from the
      victim's height in a team sporting event.

PMID- 10208343
TI  - Pathologic features of farm and tractor-related fatalities in children.
AB  - A study of 15 childhood fatalities due to farm or tractor-related accidents
      demonstrated extensive injuries typified by crushing, evisceration, and
      amputation of limbs. Although these injuries are characteristic of industrial
      accidents in adults, such accidents do not commonly occur in children. However,
      the unique circumstance of the farm, which incorporates home and industrial
      environments, results in particularly severe patterns of injuries in accidental
      childhood deaths. A knowledge of the range of machines that are used and the
      environment of the farm facilitates assessment of the types of injuries that may
      be found at autopsy in cases of pediatric farm accident.

PMID- 10208344
TI  - Fluvoxamine distribution in postmortem cases.
AB  - Four postmortem cases are reported in which the selective serotonin re-uptake
      inhibitor fluvoxamine was identified. Fluvoxamine was detectable using a standard
      alkaline drug screen, chromatographed well using a HP-1 column, and did not
      require derivitization for quantitation. Two of the cases reported were drug
      intoxications; fluvoxamine was only an incidental finding in the other 2 cases.
      Central and peripheral blood values are reported, as well as antemortem blood,
      bile, vitreous fluid, and urine values. No solid organs were obtained in any of
      the cases. Quantitations were performed using both an analytical standard and a
      fluvoxamine tablet for the preparation of calibrators. A comparison of
      quantitative values was made to evaluate the feasibility of using a tablet as the
      drug source for the preparation of calibrators when a pure reference material is
      unavailable. Postmortem peripheral blood concentrations ranged from approximately
      0.5 mg/L in a case of suicidal shooting to approximately 6 mg/L in a case of drug
      overdose. Evidence of postmortem redistribution was noted in the only case for
      which both central and peripheral blood were obtained. Quantitations using an
      extracted drug tablet for the preparation of calibrators correlated well with
      quantitations using a pure reference material.

PMID- 10208345
TI  - A fatal case of oral ingestion of benzine.
AB  - A young woman committed suicide by ingesting benzine. We report the findings
      obtained at autopsy and the chemical analyses of the gastric contents, blood, and
      tissues in this case. Fatal concentrations of n-hexane, benzene, toluene and m-,
      p-xylene were detected. Pulmonary edema and hemorrhage were caused by the primary
      effect of the chemicals or secondarily by respiratory depression, suffocation due
      to volatile fluid, or heart failure. Mild hemorrhage around arterioles and
      venules in the brain cortex suggest hyperpermeability of the vessels. The
      fragmentation and waviness of the cardiac myofibrils indicate the presence of
      hypercontraction and possibly arrhythmia.

PMID- 10208346
TI  - Heroin fatality due to penile injection.
AB  - Death due to heroin overdose and/or rapid injection of heroin is a frequent
      occurrence among opioid addicts. We present an unusual case of heroin fatality
      due to the injection of the drug in the penis. Blood, urine, bile, and vitreous
      humor concentrations of morphine were 0.68, 0.49, 0.32 and 0.062 microg/ml,
      respectively. Ethanol was detected at concentrations of 104, 124, 106, and 94
      mg/dl in the blood, urine, bile, and vitreous humor, respectively. The cause of
      death was determined to be due to heroin and ethanol intoxication.

PMID- 10208347
TI  - Death related to midazolam overdose during endoscopic retrograde
      cholangiopancreatography.
AB  - We report a midazolam-related death that occurred during endoscopic retrograde
      cholangiopancreatography (ERCP). The acute intoxication due to midazolam overdose
      was confirmed by high-pressure liquid chromatography (HPLC) analysis of the blood
      samples taken from the patient in the intensive care unit (2.8 microg/ml) and
      postmortem (2.4 microg/ml). The case strongly emphasizes the necessity of the
      precautions that should be taken when midazolam is intravenously administered.

PMID- 10208348
TI  - Tissue distribution of tramadol and metabolites in an overdose fatality.
AB  - Tramadol (Ultram) is a centrally acting, synthetic analgesic agent. Although it
      has some affinity for the opiate receptors, tramadol is believed to exert its
      analgesic effect by inhibiting the re-uptake of norepinephrine and serotonin.
      There are several published cases of tramadol's involvement in drug-related
      deaths and impairment. Reports of deaths involving tramadol alone with associated
      tissue concentrations are rare. This report documents a case in which tramadol
      overdose was identified as the cause of death. The following tramadol
      concentrations were found in various tissues: blood, 20 mg/L; urine, 110.2 mg/L;
      liver, 68.9 mg/kg; and kidney, 37.5 mg/kg. Tissue distributions of the two
      primary metabolites, N-desmethyl and O-desmethyl tramadol, are also reported. In
      each tissue or fluid except urine, the tramadol concentration was greater than
      either metabolite, consistent with other reports of drug-impaired drivers and
      postmortem cases. The O-desmethyl metabolite concentration was greater than the N
      desmethyl metabolite concentration in all tissues; this is in contrast to other
      postmortem reports, in which the majority of cases report concentrations of O
      desmethyl as less than those of N-desmethyl. This may be useful as an indicator
      of time lapse between ingestion and death.

PMID- 10208349
TI  - "Tumescent" liposuction alert: deaths from lidocaine cardiotoxicity.

PMID- 10208350
TI  - Role of the forensic pathologist in death investigation.

PMID- 10208351
TI  - Use of the Abbreviated Injury Scale to identify preventable deaths.

PMID- 10208352
TI  - Sonication lyses cells and exposes DNA for PCR amplification: potential transfer
      of technology from clinical microbiology to forensic pathology.

PMID- 10208353
TI  - Implications of attachment theory for developmental psychopathology.
AB  - Bowlby's attachment theory is a theory of psychopathology as well as a theory of
      normal development. It contains clear and specific propositions regarding the
      role of early experience in developmental psychopathology, the importance of
      ongoing context, and the nature of the developmental process underlying
      pathology. In particular, Bowlby argued that adaptation is always the joint
      product of developmental history and current circumstances (never either alone).
      Early experience does not cause later pathology in a linear way; yet, it has
      special significance due to the complex, systemic, transactional nature of
      development. Prior history is part of current context, playing a role in
      selection, engagement, and interpretation of subsequent experience and in the use
      of available environmental supports. Finally, except in very extreme cases, early
      anxious attachment is not viewed as psychopathology itself or as a direct cause
      of psychopathology but as an initiator of pathways probabilistically associated
      with later pathology.

PMID- 10208354
TI  - Emotionality and self-regulation, threat appraisal, and coping in children of
      divorce.
AB  - A model of the effects of children's temperament (negative and positive
      emotionality, impulsivity and attention focusing) on post-divorce threat
      appraisals, coping (active and avoidant), and psychological symptoms (depression
      and conduct problems) was investigated. The study utilized a sample of 223
      mothers and children (ages 9 to 12 years) who had experienced divorce within the
      last two years. Evidence was found of direct effects of child-report negative
      emotionality on children's threat perceptions and of child-report positive
      emotionality and impulsivity on children's coping. Indirect effects of negative
      emotionality on active and avoidant coping through threat appraisal were found.
      Direct effects of the temperament variables on symptoms were also found. Cross
      group analyses indicated that the models were robust to age differences, but
      gender differences were found in the relation between negative emotionality and
      depression. The results of this study indicate that temperament and threat
      appraisals are important predictors of children's post-divorce symptoms, and that
      temperament is a predictor of children's appraisal and coping process.

PMID- 10208355
TI  - Theory of mind and emotion-recognition functioning in autistic spectrum disorders
      and in psychiatric control and normal children.
AB  - The hypothesis was tested that weak theory of mind (ToM) and/or emotion
      recognition (ER) abilities are specific to subjects with autism. Differences in
      ToM and ER performance were examined between autistic (n = 20), pervasive
      developmental disorder-not otherwise specified (PDD-NOS) (n = 20), psychiatric
      control (n = 20), and normal children (n = 20). The clinical groups were matched
      person-to-person on age and verbal IQ. We used tasks for the matching and the
      context recognition of emotional expressions, and a set of first- and second
      order ToM tasks. Autistic and PDD-NOS children could not be significantly
      differentiated from each other, nor could they be differentiated from the
      psychiatric controls with a diagnosis of ADHD (n = 9). The psychiatric controls
      with conduct disorder or dysthymia performed about as well as normal children.
      The variance in second-order ToM performance contributed most to differences
      between diagnostic groups.

PMID- 10208356
TI  - Co-occurrence of conduct problems and depressive symptoms in early adolescent
      boys: III. Prediction to young-adult adjustment.
AB  - The prediction of young-adult adjustment from early adolescent conduct problems
      and depressive symptoms was examined for an at-risk sample of approximately 200
      males. Conduct problems and depressive symptoms were expected to show stability
      to young adulthood. It was predicted that early adolescent conduct problems would
      be associated with a broad range of adjustment problems in young adulthood due to
      cumulative adjustment failures. Early adolescent depressive symptoms were
      expected particularly to predict poor relationships with parents and peers.
      Additive and interactive effects of the two predictors were examined. Conduct
      problems and depressive symptoms showed significant stability to young adulthood.
      Conduct problems were associated with a broad range of adjustment problems
      including continuing problems in peer associations, substance use, self-esteem,
      relationships with parents, and new problems in noncompletion of education,
      unemployment, driver's license suspensions, and causing pregnancies. Depressive
      symptoms predicted particularly to problems in social relationships. Higher
      levels of both conduct problems and depressive symptoms in early adolescence did
      not predict to increased difficulties for any one outcome over either problem
      alone, either due to main or interaction effects. Such co-occurrence, however,
      did result in problem outcomes in multiple areas, thus, the poorest adjustment
      overall.

PMID- 10208357
TI  - Motherhood during the teen years: a developmental perspective on risk factors for
      childbearing.
AB  - The role of peer relations in childhood and behavioral and family characteristics
      in early adolescence as risk factors for adolescent childbearing was
      investigated. Sociometric surveys across third, fourth, and fifth grade and
      parent and child measures of behavioral and family functioning at sixth and
      eighth grade were collected in a lower income, urban sample of 308 African
      American females. Results replicated earlier findings on the role of childhood
      aggression as a predictor of teen motherhood. In addition, girls who displayed
      stable patterns of childhood aggression were at significantly higher risk not
      only to have children as teenagers but to have more children and to have children
      at younger ages. Results also indicated that females who were depressed in
      midadolescence were at greater risk to become parents between age 15 and 19
      years. These findings demonstrate the need to take a differentiated approach to
      understanding teen childbearing and varying developmental pathways in the
      prediction of teen motherhood.

PMID- 10208358
TI  - Developmental pathways to antisocial behavior: the delayed-onset pathway in
      girls.
AB  - Recent research has suggested that there are two distinct trajectories for the
      development of antisocial behavior in boys: a childhood-onset pathway and an
      adolescent-onset pathway. After reviewing the limited available research on
      antisocial girls, we propose that this influential method of conceptualizing the
      development of severe antisocial behavior may not apply to girls without some
      important modifications. Antisocial girls appear to show many of the correlates
      that have been associated with the childhood-onset pathway in boys, and they tend
      to show impaired adult adjustment, which is also similar to boys in the childhood
      onset pathway. However, antisocial girls typically show an adolescent-onset to
      their antisocial behavior. We have proposed that these girls show a third
      developmental pathway which we have labeled the "delayed-onset" pathway. This
      model rests on the assumption that many of the putative pathogenic mechanisms
      that contribute to the development of antisocial behavior in girls, such as
      cognitive and neuropsychological deficits, a dysfunctional family environment,
      and/or the presence of a callous and unemotional interpersonal style, may be
      present in childhood, but they do not lead to severe and overt antisocial
      behavior until adolescence. Therefore, we propose that the delayed-onset pathway
      for girls is analogous to the childhood-onset pathway in boys and that there is
      no analogous pathway in girls to the adolescent-onset pathway in boys. Although
      this model clearly needs to be tested in future research, it highlights the need
      to test the applicability of current theoretical models for explaining the
      development of antisocial behavior in girls.

PMID- 10208359
TI  - Early conduct problems and later risk of teenage pregnancy in girls.
AB  - The relationship between conduct problems at age 8 years and teenage pregnancy by
      the age of 18 years was analyzed in a birth cohort of 491 girls. A statistically
      significant association was found between early conduct problems and later risk
      of teenage pregnancy, with girls in the most disturbed 10% of the cohort having a
      pregnancy rate that was 5.3 times higher (p < .001) than the rate found in the
      least disturbed 50% of the cohort. The elevated risk of teenage pregnancy amongst
      girls with early conduct problems was in part, explained by social and family
      factors that were correlated with early conduct problems, and in part, by a
      causal chain process in which early conduct problems were associated with
      increased rates of risk taking behaviors in adolescence, which in turn led to an
      increased risk of teenage pregnancy. These results suggest that the higher rate
      of teenage pregnancy among girls with early conduct problems reflected both their
      relatively disadvantaged family backgrounds and their tendencies to risk taking
      behavior in adolescence.

PMID- 10208360
TI  - Competence in the context of adversity: pathways to resilience and maladaptation
      from childhood to late adolescence.
AB  - Competent outcomes in late adolescence were examined in relation to adversity
      over time, antecedent competence and psychosocial resources, in order to
      investigate the phenomenon of resilience. An urban community sample of 205 (114
      females, 90 males; 27% minority) children were recruited in elementary school and
      followed over 10 years. Multiple methods and informants were utilized to assess
      three major domains of competence from childhood through adolescence (academic
      achievement, conduct, and peer social competence), multiple aspects of adversity,
      and major psychosocial resources. Both variable-centered and person-centered
      analyses were conducted to test the hypothesized significance of resources for
      resilience. Better intellectual functioning and parenting resources were
      associated with good outcomes across competence domains, even in the context of
      severe, chronic adversity. IQ and parenting appeared to have a specific
      protective role with respect to antisocial behavior. Resilient adolescents (high
      adversity, adequate competence across three domains) had much in common with
      their low-adversity competent peers, including average or better IQ, parenting,
      and psychological well-being. Resilient individuals differed markedly from their
      high adversity, maladaptive peers who had few resources and high negative
      emotionality. Results suggest that IQ and parenting scores are markers of
      fundamental adaptational systems that protect child development in the context of
      severe adversity.

PMID- 10208361
TI  - Measuring developmental changes in exposure to adversity: a Life Chart and rating
      scale approach.
AB  - The reliability and validity of a comprehensive, integrative strategy for
      assessing adversity exposure in childhood and adolescence was examined in a
      community-based longitudinal study of 205 children. Extensive data from multiple
      measures completed by adolescents and their parents regarding chronic and acute
      life experiences were aggregated into a Life Chart record of lifetime adversity
      exposure. Severity of adversity in three nonoverlapping time spans was rated by
      trained judges with excellent interrater reliability. As hypothesized, Family
      adversity predominated over all other types of adversity in childhood, remained
      salient into midadolescence, and showed considerable stability over time.
      Adversity related to an individual's own behavior and psychological functioning
      rose to equal prominence by late adolescence. Adversity arising from physical
      ailments that were independent of the individual's psychological functioning
      declined over time, while adversity arising from the community rose; physical and
      community events were uncommon for most individuals but substantial for some.
      Results suggest that coherent developmental trends in adversity exposure may be
      identified effectively through judges' ratings of severity of adversity over
      multiple-year time spans.

PMID- 10208363
TI  - Effects of chronic antidepressants in an operant conflict procedure of anxiety in
      the rat.
AB  - The effects of chronic antidepressants were investigated in an animal procedure
      for the study of anxiety and anxiolytics, the conditioned suppression of operant
      behavior in rats. In daily 18-min sessions, three periods of nonpunished lever
      pressing for food alternated with two 4-min periods signaled by a light-on
      conditioned stimulus during which 50% of the responses were randomly punished by
      electric foot shocks. Antidepressants were administered once daily for 7-8 weeks
      to trained, food-restricted rats. Desipramine (dose regimen increase from 4 to 16
      mg/kg/day) induced a gradual (4-5-week latency) release of response suppression
      during punished periods over the course of several weeks of testing. This
      anxiolytic-like effect was still present 3 weeks following drug discontinuation.
      In contrast, chronic imipramine (dose regimen increase from 4 to 16 mg/kg/day),
      maprotiline (4 to 16 mg/kg/day), phenelzine (2 to 4 mg/kg/day), and fluoxetine (1
      or 8 mg/kg/day; constant dose), resulted in no change in punished responding,
      suggesting that no anxiolytic-like effect developed in the course of chronic
      treatment with these compounds. The largest dose of all antidepressants studied
      (except fluoxetine) induced a moderate to marked reduction of nonpunished
      performance that disappeared within 1 week after the last injection. A transient
      release of conditioned response suppression emerged during the week that followed
      discontinuation of imipramine, maprotiline, and fluoxetine (8 mg/kg/day). This
      apparent anxiolytic-like activity might be due to a reduction of some adverse
      effect induced by the high doses used, and/or might have resulted from a new
      dynamic equilibrium between monoamine release, reuptake processes, and
      sensitivity of postsynaptic receptors. In conclusion, operant conflict procedures
      in rats seem not particularly able to model human anxiety sensitive to chronic
      antidepressant treatments.

PMID- 10208362
TI  - Sedation and need-free salt intake in rats treated with clonidine.
AB  - The effect of intraperitoneal injection of clonidine (9-72 microg/kg) on need
      free 1.5% NaCl intake and on performance (defined as percent of a complete trial)
      in the rotarod test, was studied in normovolemic adult male rats. Clonidine (18
      and 36 microg/kg) inhibited the 1.5% NaCl intake in a 2-h test at doses that did
      not alter the performance in the rotarod test. The dose of 36 microg/kg did not
      inhibit 10% sucrose intake. Only the highest dose (72 microg/kg) of clonidine
      inhibited the 1.5% NaCl intake and the performance in the rotarod test, and
      produced signs of sedation. Sedation was determined either by change in posture
      (immobility or lack of postural tonus) of the animals during the ingestive test
      or by their performance in the rotarod test. The results suggest that sedation is
      not a determinant effect on the inhibition of 1.5% NaCl intake induced by
      clonidine.

PMID- 10208364
TI  - Diet-induced enhancement of naloxone sensitivity is independent of changes in
      body weight.
AB  - Intake of palatable solutions can enhance the anorectic potency of opioid
      antagonists. This experiment examined the relative contributions of orosensory
      experience and body weight gain to the enhanced anorectic potency of naloxone
      (0.125, 0.25, 0.5, and 1.0 mg/kg i.p.). Four groups of male hooded Lister rats
      (Charles River) were maintained on separate feeding regimes for 3 months. S-ADLIB
      rats were nondeprived with free access to lab chow and 20% (w/v) sucrose
      solution. S-RESTRICT rats received limited sucrose (50 ml/day) and chow (15
      g/day) access, yoking their body weights to ADLIB rats receiving free access to
      lab chow only. RESTRICT rats received approx. 15 g of chow/day to maintain their
      body weights at 90% of the ADLIB rats. Fifteen-minute sucrose intake tests
      revealed marked differences between naloxone sensitivity of chronic sucrose
      drinkers and sucrose-naive groups. Intakes of S-ADLIB and S-RESTRICT were
      suppressed at all doses (max suppression >60%). In comparison to animals given
      sucrose, ADLIB and RESTRICT animals were significantly less sensitive (maximum
      suppression = 35%). Naloxone potency was independent of body weight differences.
      The data demonstrate that overconsumption of palatable ingesta, and not diet
      induced weight gain, is sufficient to enhance antagonist potency. The study
      confirms that orosensory stimulation can induce plasticity in opioid systems,
      supporting an important role for opioids in intake regulation and general reward
      processes.

PMID- 10208365
TI  - Discriminative stimulus properties of ethanol in rats: studies on the role of
      nitric oxide.
AB  - The present study examined the role of the L-arginine-nitric oxide pathway in
      mediation of the ethanol interoceptive (discriminative) cue. Adult male Wistar
      rats (n = 16) were trained to discriminate ethanol (1 g/kg, 10% v/v) from saline
      under a fixed-ratio 10 (FR10) schedule of sweetened milk reinforcement. A
      nonselective nitric oxide synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl
      ester (L-NAME; 10-540 mg/kg) did not substitute for ethanol. Similarly, a
      relatively selective neuronal NOS inhibitor, 7-nitroindazole (7-NI; 10-80 mg/kg),
      did not mimic the ethanol cue. However, both L-NAME and 7-NI produced significant
      reduction in the rate of operant responding. A nitric oxide precursor, L-arginine
      (100-500 mg/kg) neither substituted for nor antagonize the ethanol stimulus.
      Taken together, these results suggest that the L-arginine-nitric oxide pathway is
      not involved in mediation of the discriminative stimulus effects of ethanol in
      the rat.

PMID- 10208366
TI  - Attenuation by nimodipine of amitriptyline-induced avoidance impairment in mice.
AB  - The effects of the dihydropyridine calcium channel blocker nimodipine on
      avoidance impairment induced by the tricyclic antidepressant amitriptyline were
      assessed during shuttle-box training and in previously trained mice of the DBA/2
      strain. Nimodipine (0, 0.5, 1, 2.5, or 5 mg/kg) had no effect alone, but
      attenuated the avoidance impairment induced by 5 mg/kg amitriptyline on avoidance
      acquisition, as well as on a previously learned avoidance response. The avoidance
      improving action of the calcium channel blocker was less evident in mice
      receiving a larger dose (7.5 mg/kg) of the antidepressant drug. The effect of
      nimodipine did not appear to be specifically related to the avoidance impairment
      induced by amitriptyline, because the calcium antagonist also attenuated the
      avoidance impairing action of the neuroleptic chlorpromazine. The avoidance
      impairment induced by amitriptyline and chlorpromazine, and the related
      ameliorating action of nimodipine, seem imputable to drug effects on the
      performance of the avoidance response, rather than to interferences with learning
      processes. The results suggest that, in the case of concomitant administration,
      nimodipine could alleviate adverse side effects of tricyclic antidepressant,
      i.e., psychomotor disturbances.

PMID- 10208367
TI  - The determination of the optimal dose of milnacipran in the olfactory
      bulbectomized rat model of depression.
AB  - Olfactory bulbectomy (OB) is associated with a variety of behavioral
      abnormalities such as hyperactivity in the "open-field" test. Previous studies
      have shown that chronic administration of antidepressants can reverse this
      behavioral deficit. The activity of milnacipran (20, 30, and 40 mg/kg, PO bid)
      administered in two equally divided doses twice daily was assessed in the
      olfactory bulbectomized rat model of depression. It was found that chronic
      treatment with milnacipran at the doses of 30 and 40 mg/kg, but not 20 mg/kg,
      attenuated the lesion-induced hyperactivity of the OB rat in the "open-field"
      test following 14 days of treatment. In the step-through passive avoidance test,
      administration of milnacipran at doses of 20, 30, and 40 mg/kg had no effect on
      the performance deficit associated with olfactory bulbectomy. Olfactory
      bulbectomy reduced the concentration of noradrenaline (NA) in the frontal cortex.
      However, chronic milnacipran treatment did not significantly alter this deficit.
      It is concluded that milnacipran, when administered chronically at doses of 30
      and 40 mg/kg, are effective at reversing the "open-field" deficit associated with
      olfactory bulbectomy, and that a dose of 30 mg/kg is an optimal dose.

PMID- 10208368
TI  - Dopaminergic projection to the nucleus accumbens mediates the memory-enhancing
      effect of angiotensins in rats.
AB  - It has been shown that the facilitatory effect of angiotensin II (AII) and its 3
      7 fragment [AII(3-7)] on cognitive processes is mediated by the dopaminergic
      system. In the present study, the involvement of dopaminergic projection to the
      nucleus accumbens (NAS) and to the nucleus septi lateralis (NSL) in the
      expression of the positive effect of AII and AII(3-7) on the retrieval of passive
      avoidance after bilateral 6-OHDA induced lesions to NAS and NSL was evaluated. To
      protect noradrenergic neurons from destruction by neurotoxin, rats were
      pretreated intraperitoneally with 25 mg/kg of desmethylimipramine, an inhibitor
      of noradrenaline uptake, 30 min before surgery. Both peptides were given
      intracerebroventricularly, at the dose of 1 nmol each, 15 min before the
      retention testing. Bilateral 6-OHDA lesions to NAS totally abolished, and to NSL
      did not affect, the positive effect of angiotensins on recall of information in a
      passive avoidance situation. Moreover, bilateral 6-OHDA lesions to NAS but not to
      NSL significantly attenuated the locomotor activity of rats in an open-field
      test. Nevertheless, it had no essential significance on the evaluation of the
      influence of the disruption of the dopaminergic endings in both structures on the
      facilitatory effect of angiotensins on retrieval process. These results suggest
      that the dopaminergic projection to NAS, but not to NSL is involved in the
      expression of the facilitatory effect of AII and AII(3-7) on memory motivated
      affectively evaluated in a passive avoidance situation.

PMID- 10208369
TI  - Haloperidol does not attenuate conditioned place preferences or locomotor
      activation produced by food- or heroin-predictive discriminative cues.
AB  - The present study examined whether a discriminative cue previously predictive of
      food or heroin reinforcement could activate and direct behavior in an environment
      that had never been paired with primary reinforcement. Olfactory cues, predicting
      the availability (S+) or unavailability (S-) of either heroin (0.1 mg/kg i.v.) or
      food (45 mg Noyes food pellets) reinforcement in the goal box of a straight-arm
      runway, were later tested in a separate environment for their ability to elicit
      locomotion (activate behavior) or induce a conditioned place preference (direct
      behavior). Presentation of the S+, but not the S-, resulted in a reliable
      increase in spontaneous locomotor activity that was not blocked by pretreatment
      with the dopamine receptor antagonist, haloperidol. Similarly, subjects displayed
      a preference for a novel location in which the S+, but not the S-, was placed.
      This preference was also unaltered by pretreatment with haloperidol. These data
      suggest that discriminative cues can profoundly affect behavior, even in
      environments that have themselves never been associated with primary
      reinforcement. Additionally, the conditioned motivational quality of these cues
      is unaltered by treatment with the same dopamine receptor antagonist shown in
      previous work to attenuate the primary reinforcing properties of heroin and food.

PMID- 10208370
TI  - Neurotransmitter system interactions revealed by drug-induced changes in
      motivated behavior.
AB  - The present article reviews studies conducted either in collaboration with Jac
      Herberg, or in parallel with those studies that used consummatory behavior and
      responding for intracranial self-stimulation (ICSS) to investigate interactions
      between neurotransmitter systems. The studies reviewed include investigations of
      the role of dopamine in 8-OH-DPAT-induced feeding; the role of 5-HT3 receptors in
      the stimulant and depressant effects of nicotine on responding for ICSS; the
      interaction of D2 and 5-HT2 antagonists in sucrose consumption, and the
      differential contributions of alpha2-adrenoceptor and 5-HT2 antagonism to the
      rapid recovery of ICSS responding from depression produced by atypical
      neuroleptics. Further studies of the role of alpha2-adrenoceptor antagonism in
      the pattern of response decrements produced by neuroleptics on schedule
      controlled responding for food confirm that the behavioral effects of monoamine
      interactions vary, depending on the specific receptor subtypes targeted and the
      behavioral paradigm employed. Consequently, the clinical relevance of findings
      will crucially depend on the choice of appropriate behavioral measures.

PMID- 10208371
TI  - A dopamine D1 agonist elevates self-stimulation thresholds: comparison to other
      dopamine-selective drugs.
AB  - The effects of the high-efficacy D1 receptor agonist SKF 81297 and the D2/3
      receptor agonist 7-OH-DPAT on brain stimulation reward thresholds and on response
      latencies in responding for the stimulation, were compared to the effects of
      subtype-selective receptor antagonists and a dopamine uptake blocker. SKF 81297
      produced dose-dependent elevations in reward thresholds but did not alter
      response latencies. In contrast, 7-OH-DPAT produced inconsistent reward threshold
      elevations, yet dose dependently increased response latencies. Both the dopamine
      D1 receptor antagonist SCH 23390 and the D2 antagonist raclopride elevated reward
      thresholds, but only raclopride significantly increased response latencies. The
      dopamine uptake inhibitor GBR 12909 lowered reward thresholds and did not
      influence response latencies. The present results provide a clear demonstration
      that a selective, high-efficacy D1 receptor agonist elevates brain stimulation
      reward thresholds without producing performance deficits. Furthermore, it was
      observed that the effects upon reward measures of D1-selective compounds, but not
      D2/D3-selective compounds, are dissociable from their effects upon response
      latency in this task. These results are discussed with regard to a distinction
      between the effects of indirect and direct dopamine agonists on reward
      thresholds, a distinction that does not depend upon the subtype-selectivity of
      the direct agonists tested.

PMID- 10208372
TI  - Specific behavioral effects related to age and cerebral ischemia in rats.
AB  - Rats at 4, 14, and 20 months of age were subjected to permanent occlusion of the
      left middle cerebral artery (MCAO) and the effects of age and ischemia assessed
      in tests for spatial learning (Morris' water maze), social behavior, olfactory
      learning, exploratory behavior, and motor function. Furthermore, the extent of
      ischemic damage to the brain of rats of 5 and 19 months of age was studied. An
      age-related decline in water-maze performance was observed, and aged rats were
      less agile, less explorative, and less frequently engaged in social interactions
      than young rats. After ischemia, mild memory impairment was observed in old rats,
      while changes in some exploratory behaviors were observed in young rats.
      Neuropathological analyses revealed a variable and limited degree of infarction
      in the piriform cortex and the insular cortex with no difference between age
      groups. In conclusion, the present study confirmed and extended current data on
      behavioral differences between young and old rats. MCAO had limited influence on
      the tested behaviors.

PMID- 10208373
TI  - Restored cognitive function in rats with combined denervations in the temporal
      region: neurochemical aspects.
AB  - During early testing (1 week), there is a clear impairment of preference for
      novelty in rats with combined transections of the fiber connections between the
      temporal and lateral entorhinal cortices and the hippocampal perforant path
      (TC/LEC + PP lesions). During late testing (2-3 weeks), a complete recovery of
      the preference for novelty is seen. The purpose of this study was to
      pharmacologically examine whether cholinergic or glutamatergic systems might
      support the processes underlying the recovery. The cholinergic antagonist
      atropine sulfate caused a complete reappearance of the impaired preference for
      novelty in rats with TC/LEC + PP transections. The glutamatergic antagonist HA
      966 only produced a moderate reactivation of the recovered lesion effect. A
      moderate impairment was also seen in intact rats treated with atropine or HA-966.
      The results suggest that blocking of cholinergic function impairs the recovered
      performance in this specific task without precluding the involvement of other
      uninvestigated neurochemical systems.

PMID- 10208374
TI  - Differences in anxiolytic-like profile of two novel nonbenzodiazepine BZ (omega)
      receptor agonists on defensive behaviors of mice.
AB  - The present experiments compared the behavioral effects of two novel BZ (omega)
      receptor agonists, the pyridazinone Y-23684 (1-30 mg/kg) and the pyrido[1,2
      a]benzimidazole RWJ-46771 (0.01-0.3 mg/kg) with the BZs diazepam (0.5-3 mg/kg)
      and clobazam (1-30 mg/kg) in the mouse defense test battery (MDTB), a model for
      the screening of anxiolytic drugs. In the MDTB, Swiss mice were confronted with a
      natural threat (a rat) and situations associated with this threat. Primary
      measures taken during and after rat confrontation were flight, risk assessment,
      defensive threat/attack, and escape attempts. Results showed that clobazam and Y
      23684 significantly modified all defense responses in the presence of the rat at
      doses that did not decrease spontaneous locomotor activity. These drugs decreased
      avoidance reactions after the rat was introduced into the runway, reduced flight
      speed and risk assessment activities of mice chased by the rat, increased risk
      assessment displayed when subjects were constrained in a straight alley, and
      reduced defensive threat and attack behaviors upon forced contact. Diazepam
      significantly decreased all but one (number of avoidances when the rat was first
      introduced into the runway) defensive behaviors. RWJ-46771 reduced risk
      assessment in the chase test, avoidance responses, flight speed, and defensive
      threat and attack reactions, but these effects occurred in the great part at
      motor-impairing doses, suggesting that the decrease in defensiveness may have
      been contaminated by behavioral suppression. Finally, following the removal of
      the rat from the runway, only Y-23684 reduced escape behavior at doses that did
      not decrease spontaneous behavior. Taken together, these findings demonstrate
      that Y-23684 displayed anxiolytic-like activity comparable to that of BZs in the
      MDTB. Although RWJ-46771 significantly modified most defensive behaviors, the
      effects may have been confounded by decreases in locomotor activity.

PMID- 10208375
TI  - Chronic fluoxetine in tests of anxiety in rat lines selectively bred for
      differential 5-HT1A receptor function.
AB  - Selective breeding for high and low sensitivity to the hypothermic response
      induced by the 5-HT1A receptor agonist 8- OH-DPAT has established two lines of
      rat (HDS and LDS, respectively) whose behavior differs in a model of depression
      and in the social interaction test of anxiety. The HDS line has a higher level of
      anxiety and, furthermore, does not display the usual anxiogenic response to
      intrahippocampal administration of 8-OH-DPAT. It was therefore hypothesized that
      this line of rat might be a useful model of high trait anxiety with a
      susceptibility to depression. We thus investigated whether chronic treatment with
      fluoxetine would result in an anxiolytic effect in the social interaction test in
      the LDS and HDS lines of rat. In both lines, acute fluoxetine (10 mg/kg) produced
      an anxiogenic effect in the social interaction test; when rats were tested 24 h
      after 14 days of fluoxetine treatment there were no anxiolytic effects in either
      line. In the social interaction test, chronic fluoxetine treatment did not change
      either the anxiogenic effect of 8-OH-DPAT (100 ng) injected bilaterally into the
      dorsal hippocampus in the LDS line or the lack of response in the HDS line. In
      the elevated plus-maze, chronic fluoxetine treatment resulted in a significant
      anxiogenic effect in the HDS line, but was without effect in the LDS line.
      Intrahippocampal 8-OH-DPAT was without effect in the plus-maze in either line.
      These results suggest that chronic treatment with fluoxetine did not modify the
      hippocampal 5-HT1A receptor in either line. The anxiogenic effects observed in
      the plus-maze in the HDS line after chronic fluoxetine might relate to line
      differences in 5-HT1A receptors in other brain regions.

PMID- 10208376
TI  - Dose dependency of sex differences in the effects of repeated haloperidol
      administration in avoidance conditioning in mice.
AB  - Sex differences in the effects of haloperidol in active avoidance conditioning in
      mice have previously been found in various studies carried out in our laboratory.
      Males were more affected than females by the disruptive effects of this
      neuroleptic. The work described here broadens the study of these sex differences
      to higher doses of haloperidol (0.1 and 0.2 mg/kg) using a repeated
      administration schedule (5 days). The results did not show sex differences in the
      deteriorating effects of this dopamine antagonist in the escape-avoidance
      response, but a tendency in the number of nonresponses was observed in the same
      direction as former results: male animals were more sensitive than females to the
      inhibitory effect of the low dose of haloperidol. It is concluded that the
      appearance of sex differences in the effects of haloperidol on active avoidance
      conditioning is a dose-dependent phenomenon.

PMID- 10208377
TI  - Estrogen improves working but not reference memory and prevents amnestic effects
      of scopolamine of a radial-arm maze.
AB  - This study investigated the effect of estrogen treatment on working memory and
      reference memory of female rats. In addition, the impact of estrogen on the
      sensitivity of these two types of memory to the cholinergic antagonist
      scopolamine was investigated. At 35 days of ages, rats were ovariectomized and
      implanted chronically with Silastic capsules containing either 25% crystalline
      estradiol or 100% cholesterol. Thirty days after surgery, animals were trained on
      an eight-arm radial maze with four arms baited to assess both working and
      reference memory performance. Following training, females were given scopolamine
      hydrobromide (0.2 mg/kg i.p.) prior to retesting on the task. Results indicated
      that estrogen treatment improved working memory performance during maze
      acquisition but did not affect reference memory performance. Scopolamine
      treatment impaired performance on the working memory component, but not the
      reference memory component, while estrogen prevented the impairment of working
      memory by scopolamine. Results support previous evidence that estrogen
      selectively enhances performance on tasks that depend on working memory.

PMID- 10208378
TI  - Effects of diazepam or chronic alcohol treatment on spatial reversal learning in
      mice.
AB  - Mice submitted to chronic alcohol consumption (CAC; 11 months) or to systemic
      diazepam administration were trained in a spatial reversal learning task.
      Although CAC-treated mice were able to learn the initial acquisition at normal
      rates, they were impaired during the first reversal of the discrimination and
      subsequent reversal sessions. In contrast, diazepam administration induced no
      deficits for any behavioral measure. In conclusion, CAC, but not diazepam
      administration, induces an exaggerated sensitivity to proactive interference. The
      two treatments spared, however, the development of the learning set curve. These
      results are congruent with clinical data showing that nondeclarative or implicit
      forms of memory processes are spared in diazepam-treated subjects or in chronic
      alcoholics.

PMID- 10208379
TI  - Behavioral effects of diazepam in the murine plus-maze: flumazenil antagonism of
      enhanced head dipping but not the disinhibition of open-arm avoidance.
AB  - Although it is widely believed that benzodiazepines reduce anxiety through
      positive allosteric modulation of the GABA(A)-chloride channel complex, this is
      not the only mechanism through which agents of this class can modify CNS
      function. Furthermore, a significant number of reports of apparent flumazenil
      blockade of diazepam anxiolysis in animal models have paid limited attention to
      possible intrinsic behavioral actions of the antagonist per se. In the present
      study, ethological methods were employed to assess in detail the effects of
      diazepam, flumazenil, and their combination on the behavior of male DBA/2 mice in
      the elevated plus-maze paradigm. In two experiments, diazepam (1.5 mg/kg) alone
      reduced open-arm avoidance and increased head dipping, whereas flumazenil (10-40
      mg/kg) alone was without significant behavioral effect. However, with the sole
      exception of head dipping, prior administration of flumazenil (10 and 40 mg/kg)
      failed to block the behavioral effects of diazepam under present test conditions.
      These findings imply that the anxiolytic effects of diazepam in the mouse plus
      maze are not mediated through flumazenil-sensitive benzodiazepine receptors and
      that alternate mechanisms must be considered.

PMID- 10208380
TI  - TCDD-induced anorexia and wasting syndrome in rats: effects of diet-induced
      obesity and nutrition.
AB  - Interactions of diet and diet-induced obesity, and the characteristic wasting
      syndrome caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were studied in
      TCDD-resistant Han/Wistar and TCDD-sensitive Long-Evans rats. The rats were made
      obese by feeding them either a high-energy diet (consisting of chocolate, cheese,
      and chow) or force feeding. TCDD reduced body weight in a parallel manner in lean
      and obese rats. The high-energy diet diminished the body weight loss and
      increased the survival time in L-E rats after a lethal dose of TCDD, while energy
      supplement with high-fat/low-protein food had an opposite effect. In conclusion,
      diet-induced obesity and TCDD had additive effects on body weight. Dietary
      manipulations were able to modify the weight loss and survival time after TCDD.
      Fat seems to have a negative impact, while carbohydrate or protein may have a
      positive impact in this respect. The results are in agreement with a view that
      TCDD-exposed rats have a negative fat balance favoring fat loss.

PMID- 10208381
TI  - Blockade of nicotine self-administration with nicotinic antagonists in rats.
AB  - The reinforcing properties of a variety of drugs abused by humans have been
      investigated using the technique of intravenous self-administration in the rat.
      To examine the effect of nicotine dose on nicotine self-administration, Wistar
      rats were allowed to self-administer various doses of nicotine using a within
      subjects Latin square design. An inverted U-shaped dose response curve was
      obtained, with the highest rates of responding at the 0.03 mg/kg/inf dose. With 1
      h daily nicotine self-administration sessions, rats did not appear dependent on
      nicotine 24 h later, as indicated by the absence of somatic signs of withdrawal
      after subcutaneous injection of a nicotinic acetylcholine receptor antagonist,
      mecamylamine (0.57 mg/kg). In another set of studies, pretreatment with
      subcutaneous mecamylamine or dihydro-beta-erythroidine, two nicotinic
      acetylcholine receptor antagonists, resulted in significant dose-dependent
      reductions in nicotine self-administration, at two nicotine doses (0.03 and 0.06
      mg/kg/inf). These results indicate that nicotine is an effective reinforcer in
      Wistar rats under the present parameters, and that these reinforcing effects are
      mediated by activation of nicotinic acetylcholine receptors.

PMID- 10208382
TI  - Skin substitutes in burns.

PMID- 10208383
TI  - Modulating the functions of neutrophils and lipid peroxidation by FK506 in a rat
      model of thermal injury.
AB  - Neutrophils diffusely invade lung, liver, kidney, intestine, muscle and burned
      skin following burn injury. To ameliorate this invasion and minimize its effects,
      neutrophils can be modulated by giving neutrophil inhibitors and modulators. In
      this study, FK506 was used to decrease neutrophil infiltration and lipid
      peroxidation in remote organs (lung, liver, kidney and intestine) in a burned rat
      model. FK506 is a new major immunosuppressive agent that is known to modulate
      neutrophils during inflammation. Neutrophil infiltration was assessed indirectly
      by measuring myeloperoxidase (MPO) activity biochemically in remote organs
      following 30% full thickness burn injury. Malondialdehyde (MDA), the end product
      of lipid peroxidation, was measured biochemically in remote organs and plasma to
      determine if there is a relationship between neutrophil infiltration and lipid
      peroxidation after burn injury. FK506 was given intramuscularly at the dose of
      0.5 and 1.0 mg/kg for three days before burn injury. Thermal trauma to the skin
      caused a statistically significant increase in MPO activity and MDA content in
      remote organs. FK506 was effective in reducing lipid peroxidation and neutrophil
      infiltration especially at 24 h postinjury in lung, liver and kidney. FK506 may
      have some benefit (prophylactic) in reducing systemic neutrophilic injury and
      related lipid peroxidation in burns.

PMID- 10208384
TI  - The effect of antioxidant therapy on cell-mediated immunity following burn injury
      in an animal model.
AB  - Although antioxidant therapy has been introduced into early post burn protocols
      to prevent oxidative injury, it is still not known how they effect the cellular
      immunity which was already depressed due to thermal injury. To investigate the
      effect of antioxidant therapy on postburn immunosuppression following burn injury
      in a rat model, well known antioxidants: allopurinol (50 mg/kg/day),
      desferrioxamine (15 mg/kg/day), PEG-catalase (PEG-CAT) (1200 U/kg/day), N
      acetylcysteine (NAS) (1 mg/kg/day) and vitamin-C (Vit-C) (0.5 mg/kg/day) were
      given for 7 days following thermal injury. The immunologic status of the rat was
      studied using two in vivo measures at seventh day following (30% TBSA) full
      thickness burn injury. The contact hypersensitivity response (CHR) of rats, and
      their ability to induce a host versus graft reaction (HVGR) in the popliteal node
      were used to assess immune system as in vivo measures. The use of mentioned
      antioxidants resulted in significant improvement (between P < 0.05 and P < 0.001)
      of burn induced immunosuppression as reflected by CHR. The treatment with
      allopurinol and PEG-CAT (P < 0.01) significantly improved, while desferrioxamine,
      NAS and Vit-C improved, but not significantly, HVG reaction in burned rats. This
      study demonstrated that a large burn was profoundly immunosuppressive and early
      intervention of antioxidant therapy was able to significantly restore cell
      mediated immunity as reflected by two in vivo assays.

PMID- 10208385
TI  - Expression of midkine in normal and burn sites of rat skin.
AB  - Expression of midkine (MK), a retinoic acid-inducible heparin binding growth
      factor, was examined immunohistochemically in normal and burn sites of rat skin.
      In the normal skin, MK was localized in the epidermis and dermal appendages such
      as hair follicles and sebaceous glands. Mast cells in the subdermal connective
      tissue also accumulated MK. After burn injury, MK-positive cells began to
      infiltrate into subdermal connective tissue, and the number of MK-positive cells
      in the region increased to a maximum at postburn day two and then decreased
      gradually. Western blotting analysis of both normal and postburn skin revealed a
      30 kDa band reactive with anti-MK antibody; this band was concluded to be a dimer
      of MK. These findings were discussed from the viewpoint of the possible role of
      MK in wound healing.

PMID- 10208386
TI  - Inhibitory effects of tachykinin receptor antagonists on thermally induced
      inflammatory reactions in a rat model.
AB  - Recent studies have proposed that activation of the sensory nervous system after
      thermal injury induces the release of vasoactive neuropeptides, including
      tachykinins which contribute to the local inflammatory reaction as well as to the
      nociceptive transmission at the spinal cord level. Effects of the tachykinins
      substance P and neurokinin A are mediated by the neurokinin 1 and 2 (NK1, NK2)
      receptors. The aim of the present study was to investigate the modulatory role of
      NK1 and NK2 antagonists on edema formation, and on hindpaw withdrawal latency to
      experimentally asses nociception. Thermal injury was inflicted on the
      anaesthetized rat by dipping the right hindpaw into hot water at 60 degrees C for
      20 s. The amount of edema formation was calculated by measuring the hindpaw
      volume with a plethysmograph before and during 420 min after scalding. In other
      studies scalding was inflicted under brief anesthesia, and hindpaw withdrawal
      latencies (HWL) to mechanical stimulation were recorded before injury and at 180
      min after. The effect on edemic reactions of rats treated locally with NK1 and
      NK2 receptor antagonist were studied, as well as the effect of the same compounds
      on HWL after intrathecal injection. Scalding induced a progressive edema
      formation which was reduced significantly in rats treated with local injection of
      100 nmol of NK1 and NK2 antagonists 45 min after the injury. The thermally
      induced inflammation was followed by significant decrease of the latency of
      hindpaw withdrawal response to mechanical stimulation. Intrathecal injection of
      30 nmol of the same drugs 180 min after scalding was followed by significant
      increase in HWL. The results indicate that SP and NKA contribute to the
      inflammatory reactions after thermal injury and that the tachykinin receptor
      antagonists possess the ability to reduce both the local edemic reaction as well
      as the nociceptive transmission at the spinal cord level.

PMID- 10208387
TI  - Changes in circulating levels of interleukin 6 in burned patients.
AB  - Interleukin 6 (IL-6) levels in serial serum samples of 10 burned patients were
      analyzed. The total body surface areas (TBSA) of the burn injury varied from 30
      to 85%. Among these 10 patients, five recovered and the other five, who were
      septic, expired. A significant difference in serum IL-6 values on admission (5-13
      h postburn) was found (p < 0.05) between patients who survived or died from burn
      injury as analyzed by the Wilcoxon's rank sum test. In addition, a significant
      difference in serum IL-6 on admission was also found (p < 0.05) between patients
      with TBSA of greater or less than 50%. Afterwards, an initial peak serum IL-6
      response was detected within 4 days postburn. Significant differences in the peak
      serum IL-6 levels were not found between patients with TBSA of greater or less
      than 50% and patients who survived or expired from burn injury. In the survivors,
      serum IL-6 remained low, while IL-6 increased markedly starting at about one to
      two weeks postburn in four of the five nonsurvivors with proven sepsis. Except
      for the patient who expired 42 days postburn, the maximum serum IL-6 values of
      the other four nonsurvivors were all greater than those of the five survivors
      from burn injury. Significant correlation (p < 0.05) relating the change in serum
      IL-6 and body temperature was observed in only two (one survivor and one
      nonsurvivor) of the ten patients. Changes in serum IL-6 were also compared with
      changes in circulating TNF-alpha and IL-8 determined previously. A similar
      pattern in the dynamic changes of circulating TNF-alpha, IL-8 and IL-6 was
      observed in the individual burned patient. An increase in serum levels of all
      three cytokines was detected postburn. Serum levels of three cytokines were
      significantly higher in the septic patients, who all died. It was considered that
      all three cytokines analyzed may play a significant role in the pathophysiology
      of sepsis in burned patients.

PMID- 10208388
TI  - The effect of burn subeschar tissue fluid on skeletal muscle and hepatic amino
      acid uptake in an experimental system in vitro.
AB  - Burn injury is associated with major metabolic disturbances. Many factors or
      mediators are responsible for post-burn metabolic changes. The present study was
      designed to test the role of interstitial edema fluid from burn eschar in
      regulating amino acid transport into hepatic and muscle tissue. Subeschar tissue
      fluid (SEF) was collected from just under the full thickness burn area. Amino
      acid transport, determined as the uptake of [3H]-alpha-aminoisobutyric acid by
      incubated soleus muscles or liver slices in vitro, was reduced after the addition
      of subeschar tissue fluid. The suppression was more marked with fluids taken from
      patients with a large burn area. Significant findings were noted when the total
      surface burn area was more than 70%. There were significant differences in the
      SEF suppression effect between survivors and non-survivors, but not between
      inhalation and non-inhalation victims. The results suggest the presence of one or
      more factors in subeschar tissue fluid that inhibit both muscle and liver amino
      acid transport. The data also suggest that the inhibitory factors are most likely
      produced by the burned tissue. This suppression effect may be beneficial to burn
      victims in maintaining near-normal vascular osmolarity by way of an increased
      plasma amino acid level.

PMID- 10208389
TI  - Correlation between fungi isolated from burn wounds and burn care units.
AB  - A comparison was made prospectively between fungal isolates from patients and
      burn care units. Aspergillus niger was the most frequent isolate in both patients
      and burn care units whereas Ulocladium was the commonest isolate in the control
      group. Aspergillus terreus, Penicillium and Zygomycetes, which were recovered
      from burned patients, were also found more frequently in the burn care units than
      in the control group (other areas in the hospital). These findings indicate a
      potential risk of fungal infection which can be acquired from the immediate
      surroundings of patients in burn care units. Periodical burn ward decontamination
      is therefore recommended.

PMID- 10208390
TI  - Paediatric burns in Iceland. Hospital admissions 1982-1995, a populations based
      study.
AB  - Epidemiological data of 290 children admitted to the Paediatric Department,
      University Hospital of Iceland, over a 14 year period, 1982-1995, are presented.
      The sex ratio boys/girls was 1.6. 72.8% were children four years and younger. Hot
      fluids was the most common cause of burn injuries, mostly caused by geothermal
      hot water. Only one child suffered from electricity burn injuries and none from
      corrosives. Most of the accidents occurred at home (81.4%). A decreasing number
      of children suffering from electricity and corrosive burn injuries reflects
      heightened awareness and improved safety in the home. We found a significant
      increase in the incidence of hot fluid burn injuries in Icelandic children
      compared to previous studies. This calls for preventive measures with regard to
      geothermal and other hot water burns in Icelandic children.

PMID- 10208391
TI  - Care of burns victims in Europe.
AB  - There is no detailed information about the care of burns victims, in Europe, in
      the case of a fire disaster. Several countries have discussed how to treat burn
      victims, but only a little is known of their capacity to offer space to other
      countries in the event of a fire disaster outside the country in question. In
      Europe, most countries are dependent on England, France and Germany in such
      cases. Since "Los Alfaques", "Ramstein" and other examples of such disasters, we
      know how important it is to focus more on burn victims in Europe with respect to
      national and international cooperation.

PMID- 10208392
TI  - Patients with suicidal burns and accidental burns: a comparative study of socio
      demographic profile in India.
AB  - This is a prospective study of 50 consecutive admissions to the burns unit. The
      socio-demographic data was collected using special proforma and interviewing the
      patients and relatives. All patients were administered the presumptive stressful
      life event scale (PSLES). Depending on the presence or absence of suicidal
      intent, patients were divided into two groups. The two groups were then compared
      with regards to their socio-demographic profile using the unrelated t-test and
      the Fisher's exact test. The two groups did not differ significantly with regards
      to age, sex, education, marital status, occupation or monthly per capita income.
      The patients who had suicidal intent came from joint family, had more stressful
      life events and suffered larger burns injuries compared with those who
      experienced accidental burn injuries. The majority of the patients were below the
      age of 35, unemployed and females outnumbered males in both the groups.

PMID- 10208393
TI  - Prestorage leukocyte filtration may reduce leukocyte-derived bioactive substance
      accumulation in patients operated for burn trauma.
AB  - Adverse effects of perioperative blood transfusion appear to be storage-time
      dependent and may be related to extracellular accumulation of bioactive
      substances in blood products. In this study the clinical effects of leukofiltered
      and non-filtered blood products in patients undergoing surgery for burn trauma
      are investigated. 24 consecutive patients were randomly selected to receive
      transfusion with non-filtered blood components (group A, n = 12) or similar
      products, which were prestorage leukofiltered (group B, n = 12). The burn injury
      was scored using the Bull and Fischer index of age and burn surface area.
      Histamine, interleukin-6 (IL-6), plasminogen activator inhibitor-1 (PAI-1),
      eosinophil cationic protein (ECP) and myeloperoxidase (MPO) were analysed in
      plasma or serum collected from all patients 30 min before skin incision, at skin
      incision and 5, 10 and 30 min and thereafter every 30 min after skin incision
      until the grafts were secured by wrapping. Samples were also taken 8 h after skin
      incision and in the morning of postoperative days 1-5. The amount of blood
      products transfused from admission until day 5 postoperatively was recorded. All
      patients were followed until discharge or death. The Bull and Fischer index was
      comparable in the two groups. Prestorage leukofiltration reduced the amount of
      blood products required for transfusion significantly (p < 0.05) compared with
      non-filtered products. The levels of the various bioactive substances changed
      during and after the operation. In particular, ECP and MPO levels increased
      significantly (p < 0.05) in group A patients compared with unchanged (ECP) or
      decreased (MPO) levels in group B patients. IL-6 analyses showed, that the trauma
      had more severe impact on group B patients than on group A patients.
      Nevertheless, 4 patients died in group A and 2 in group B; all with a Bull and
      Fischer index between 1.0 and 2.0. Prestorage leukocyte filtration may reduce
      transfusion related accumulation of various bioactive substances and the
      requirement for blood in burn trauma patients.

PMID- 10208394
TI  - Acute renal failure in severely burned patients.
AB  - Acute renal failure (ARF) is a well known complication of severe burns and is an
      important factor leading to an increase in mortality. In order to analyze
      possible pathogenetic and prognostic factors associated with ARF in burned
      patients we reviewed in a retrospective study the files of 328 patients with
      burns > 10% body surface area (BSA), admitted to our burn unit between 01.01.94
      and 01.05.98. We found 48 patients with acute renal failure corresponding with an
      incidence of 14.6%. Patients with ARF had a mean burned surface area of 48% (13
      95) and an abbreviated burn severity index score (ABSI) of 9.8 (4-15). Thirty
      eight (79%) of these patients had an inhalation injury diagnosed. Renal
      insufficiency was divided in a late and an early form depending on its time of
      onset and we found 15 (31%) patients with ARF occurring within the first 5 days
      of the hospital stay and 33 (69%) patients with ARF developing >5 days following
      the thermal injury. The incidence of myoglobinuria and hypotension during the
      resuscitation phase was significantly higher in the group with early ARF, whereas
      patients with late ARF presented sepsis more frequently than patients with early
      occurring renal failure. Accordingly, potential nephrotoxic antibiotics were
      administered more often in patients with late ARF. Patients with ARF were treated
      by continuous arteriovenous hemofiltration (CAVH) for a mean period of 10.5 days
      (1-47) and CAVH was associated with a complication rate of 10%. Most of the
      complications were associated with the vascular access in the femoral artery. The
      mortality rate in patients with ARF was 85% and death was due to multiple organ
      failure in 83% of the cases. Only burned BSA and inhalation injury proved to be
      significantly correlated with the development of ARF, whereas age, third degree
      burn or electric injury were not significantly different between the two groups.
      Neither age, TBSA, day of onset of ARF nor duration of the renal replacement
      therapy proved to be significantly different comparing survivors with non
      survivors, and thus predictive for the survival rate.

PMID- 10208395
TI  - Cost effectiveness of skin substitutes. A commentary on the debate at the 10th
      ISBI Congress, Jerusalem 1998. International Society for Burn Injuries.

PMID- 10208396
TI  - Scalp burns in elderly women--the perils of the perm.

PMID- 10208397
TI  - Burns due to aerosol can explosion.

PMID- 10208398
TI  - Burns due to anti-lice lotion.

PMID- 10208399
TI  - A career threatening incident during a burns debridement.

PMID- 10208401
TI  - Recent references.

PMID- 10208400
TI  - Blood platelets in severely injured burn patients.

PMID- 10208402
TI  - A new in vitro model to study interaction between whole blood and biomaterials.
      Studies of platelet and coagulation activation and the effect of aspirin.
AB  - We have developed a versatile in vitro chamber model with a double purpose:
      first, to be able to study mechanisms of bio-incompatibility, and, second, to
      test biomaterials at all levels of interactions, in whole blood. The use of
      biomaterials in the form of microscope slides as walls in the chamber makes it
      possible to analyse both the biomaterial surface with regard to protein and cell
      binding, as well as the molecular events taking place in the fluid. Incubation of
      blood in the chamber, for 60 min at 37 degrees C resulted in the rapid binding of
      complement and coagulation proteins and of leukocytes and platelets to
      polyvinylchloride (PVC) slides. The cells formed a layer which more or less
      covered the underlying surface. Unlike complement activation, as reflected by
      soluble C3a and C5b-9, the thrombin-antithrombin formation was completely
      nullified in cell-depleted plasma. Despite the fact that thrombin-antithrombin
      generation was also negligible in platelet-rich plasma, inhibition of platelet
      aggregation on the material surface with aspirin resulted in suppressed
      generation of thrombin antithrombin complexes. Taken together, the coagulation
      activation in the chamber was dependent on the presence of blood cells which
      suggests that bound/aggregated platelets initiate a sequence of events involving
      leukocytes that results in coagulation activation.

PMID- 10208403
TI  - Influence of polyglactin-coating on functional and morphological parameters of
      polypropylene-mesh modifications for abdominal wall repair.
AB  - Regarding oversized mechanical properties of most of the currently available
      materials a new mesh was developed (ETHICON, Norderstedt, Germany) and exactly
      adopted to the physiology of the human abdominal wall by reducing the amount of
      polypropylene (weight of <30 g/m2; mesh A). The consecutive increase of pores
      size as well as the use of multifilaments led to a pronounced increase of
      flexibility. To improve the handling during operation the initial stiffness of
      this low-weight large pores mesh was increased by strengthening with different
      amounts of absorbable polyglactin (combination of glycolide and lactide) in
      various forms: by coating (mesh B), adding multifilament polyglactin filaments
      (mesh C, Vypro) or both (mesh D), respectively. To test the consequences of the
      different supplementary techniques all mesh variants are implanted in a rat
      model. Over implantation intervals of 3, 7, 14, 21 and 90 days we measured the
      tensile strength, the resulting stiffness and surveyed the tissue response,
      particularly in regard to the extent of inflammation and to the induced fibrosis.
      The results proved a sufficient mechanical stability of the material reduced and
      pure polypropylene mesh A without restriction of the mobility of the abdominal
      wall compared with a group that had simple laparotomy and closure. The
      histological analysis of the interface showed a minor inflammatory reaction and a
      dense vascularisation. The addition of polyglactin multifilaments (mesh C)
      reduces the number of macrophages and granulocytes as indicators for acute
      inflammation, showing generally a scar formation limited merely to the
      perifilamentary region. The abdominal wall compliance remained unchanged compared
      with mesh A. The coating of the polypropylene with polyglactin (mesh B and D)
      appeared to change the tissue reaction remarkably, favouring the formation of a
      connective tissue capsule around the whole mesh. The mechanical testing revealed
      an apparent protrusion with an increase of curvature of the artificial abdominal
      wall at rising intraabdominal pressures. The entire coating of the polypropylene
      surface with polyglactin induces an all embedding scar plate, filling out the
      pores and forming a tissue capsule. The complex interaction of tissue and
      implanted biomaterials with their distinct alterations of the tissue response
      confirms the necessity of in vivo experiments even after 'minor' modifications.
      Whereas the addition of polyglactin filaments appears to be favourable, the
      coating of polypropylene with polyglactin seems to hinder the incorporation of
      the mesh.

PMID- 10208404
TI  - Induction of macrophage apoptosis by ceramic and polyethylene particles in vitro.
AB  - The purpose of this study was to investigate in vitro the presence of apoptotic
      cell death after macrophage stimulation with different ceramic (Al2O3 and ZrO2)
      and high density polyethylene (HDP) particles. We also analyzed the effects of
      particle size, concentration, and composition. The J774 mouse macrophage cell
      line was exposed to commercial particles of different sizes (up to 4.5 microm)
      and concentrations (up to 500 particles per macrophage). Fluorescence microscopy
      and DNA laddering were used to investigate the presence of apoptosis in cell
      cultures after 24 h of incubation. Fluorescence microscopy of propidium iodide
      stained cells showed two characteristic morphological features that occur in
      apoptotic cells, namely nuclear condensation and heterogeneity of stain uptake.
      The effect of ceramic particles on apoptotic nuclear morphology was size- and
      concentration-dependent and reached a plateau above 150 particles per macrophage
      at 1.3 microm. With regards to composition, we did not find any difference in
      cell morphology between Al2O3 and ZrO2. Ceramic and HDP particles induced DNA
      fragmentation into oligonucleosomes as evidenced by DNA laddering, another
      characteristic of apoptosis. The induction of DNA laddering was size- and
      concentration-dependent whereas particle composition (Al2O3 vs. ZrO2 and Al2O3
      vs. HDP) had no effect. In conclusion, our results demonstrated that ceramic and
      HDP particles induce macrophage apoptotic cell death in vitro and open doors for
      possible modulation of debris-induced periprosthetic osteolysis.

PMID- 10208405
TI  - The corrosion behaviour of Ti-6Al-4V, Ti-6Al-7Nb and Ti-13Nb-13Zr in protein
      solutions.
AB  - Ti alloys are used in orthopaedic applications owing to their appropriate
      mechanical properties and their excellent corrosion resistance. The release of
      titanium and the other alloying elements into the surrounding tissue has been
      reported due either to passive corrosion or accelerating processes such as wear.
      Since the passive layer can be broken down in certain circumstances by wear it is
      important to study the ability of these alloys to repassivate in biological
      environments, in particular in the presence of proteins, and evaluate how the
      repassivated surface may vary from the original surface. In this study we
      investigated the ability of Ti-6Al-4V, Ti-6Al-7Nb and Ti-13Nb-13Zr to repassivate
      in phosphate buffered saline (PBS), bovine albumin solutions in PBS and 10%
      foetal calf serum in PBS at different pH values and at different albumin
      concentrations. It was found that an increase in pH had a greater effect on the
      corrosion behaviour of Ti-6Al-4V and Ti-6Al-7Nb than on Ti-13Nb-13Zr in PBS and
      that the addition of protein to the PBS reduced the influence of pH on the
      corrosion behaviour of all the alloys. The effect of the corrosion and
      repassivation was investigated by measuring changes in the surface hardness of
      the alloys and it was found that corrosion reduced the hardness of the surface
      oxides of all the alloys. In PBS the reduction was smallest for Ti-6Al-4V and
      largest for Ti-13Nb- 3Zr and that corrosion in protein solutions further reduced
      the hardness of the surface oxides. This effect was greater for Ti-6Al-4V and Ti
      6Al-7Nb than for Ti-13Nb-13Zr. In conclusion, proteins in the environment appear
      to interact with the repassivation process at the surface of these alloys and
      influence the resulting surface properties.

PMID- 10208406
TI  - Incorporation of three types of bone block implants in the facial skeleton.
AB  - The regenerative response on autogenous cancellous and cortical bone grafts, and
      on a commercial available xenogenous resorbable bone mineral (RBM) (Bio-Oss,
      Geistlich-Pharma, Wolhusen, Switzerland) was compared in standardized bony
      defects related to a paranasal sinus. On 15 skeletally mature goats four critical
      sized full thickness bone defects were trephined in the frontal bone. These
      defects were filled at random with a cortical bone plug, a cancellous bone plug,
      a plug of spongious RBM cut into shape or left empty. Fluorochrome bone markers
      were injected subcutaneously 1 and 5 weeks after transplantation, and one week
      before the animals were killed. The animals were killed at 3, 6, 12 and 24 weeks
      after surgery. Histological evaluation showed that autogenous bone grafts were
      all accepted and incorporated in a similar way as in calvarial defects. RBM was
      only osteoconductive. New bone was formed at the margins of the defects, and only
      little of the RBM was incorporated. Most of the RBM was gradually resorbed by
      multinucleated osteoclast-like cells.

PMID- 10208407
TI  - Spectroscopic investigation of tertiary fold of staphylococcal protein A to
      explore its engineering application.
AB  - Staphylococcal protein A is a cell wall constituent of most strains of
      Staphylococcus aureus, and it is characterized by its binding affinity to some
      immunological classes. A mutated low molecular weight type protein A (LPA; Mwt =
      27 kDa) which consists of the domains, E, D, A, B and 13 residues of the C-domain
      was prepared in this study. Since LPA does not possess a cell wall-bound region
      in contrast to wild-type protein A (WPA; Mwt = 42 kDa), we have established a
      methodology of large scale purification of LPA without using any extracellular
      expression systems such as Escherichia coli. Using this relatively abundant
      protein, the immobilization of the LPA with silk fibroin of Bombyx mori was
      performed. Thermal stability of LPA immobilized with silk fibroin is higher than
      that of free LPA at high temperature judging from the immunoglobulin G (IgG)
      binding affinity. However, the apparent value of its affinity decreased relative
      to that of immobilized WPA. These results indicate that structural information is
      essential to explore improvement of IgG-binding affinity of immobilized LPA.
      Therefore, secondary structure of free LPA was detected by its characteristic
      helical pattern in circular dichroism (CD) in aqueous solution. In addition to
      this, tertiary fold of four IgG-binding domains were investigated by two
      dimensional 1H-NMR spectra. Four significantly high-field shifted cross-peaks
      attributed to methyl signals of alanine residues suggest that all four domains
      pack into a three helix bundle motif in solution. These structural data and
      properties of IgG-binding affinity suggest that spatial arrangement of four IgG
      binding domains are packed into a compact globular molecular shape. This causes a
      certain active site of immobilized LPA to be buried in the silk fibroin fiber.

PMID- 10208408
TI  - Effects of PVC bags sterilization process on the 5-fluorouracil stability.
AB  - The stability and compatibility of 5-fluorouracil (5-FU) in undiluted or diluted
      admixtures stored in beta-radiation sterilized portable poly(vinyl chloride)
      (PVC) infusion bags were investigated. Admixtures containing 5-FU 50 mg ml(-1)
      not diluted or 25 mg ml(-1) diluted in 0.9% sodium chloride injection were placed
      in 100 or 250 ml empty PVC reservoirs sterilized initially by beta-irradiation.
      They were protected from light and placed at 37 degrees C. Two ml quantities were
      withdrawn immediately after preparation and after storage for 1, 2, 3, 4, 5, 6, 7
      and 14 days. For each condition, samples from each admixture were tested for drug
      concentration by stability-indicating high-performance liquid chromatography. The
      admixtures were also monitored for precipitation, color change and pH.
      Evaporative water loss from the containers was also measured. 5-FU was compatible
      with PVC containers in all tested conditions for 14 days. No loss of drug and no
      color change were detected throughout the storage period. pH values were stable
      and neither precipitation nor loss of water through the reservoirs was observed
      when drug 50 or 25 mg ml(-1) (diluted using 0.9% sodium chloride) was stored in
      100 ml capacity polyvinyl PVC bags. However, when stored in 250 ml capacity PVC
      bags, the 5-FU solution showed precipitation after 13 and 14 days of storage, but
      no drug loss was detected due to a substantial loss of water. The precipitation
      of the drug was due to the decrease of pH induced by the dehydrochlorination of
      PVC during beta-irradiation leading to the formation of hydrochloric acid in
      solution. Differences observed between 100 and 250 ml capacity bags can be
      explained by the greater area of PVC present in 250 ml reservoirs, and
      consequently more HCl formed. Finally, more plasticizer, di-(2-ethylhexyl)
      phthalate (DEHP), was then detected in drug solutions stored in 250 ml PVC bags.
      So, we recommend the use of 100 ml bags to store 5-FU at longer storage times and
      higher temperatures.

PMID- 10208410
TI  - Biologic response to passive dissolution of titanium craniofacial microplates.
AB  - The effect of anodization on passive dissolution of titanium was studied by
      measuring titanium levels in peritoneal leukocytes and tissues of laboratory
      animals with titanium plates implanted into the peritoneal cavity. Fifteen
      Sprague-Dawley rats were assigned randomly to three treatment groups of five
      animals. One group served as controls, the other two groups had an anodized or an
      unanodized implant placed in the left paracolic gutter. Peritoneal lavage samples
      and blood samples, organ tissues and tissue surrounding the implants, were
      removed for histologic examination and titanium levels. Titanium was not detected
      in any distant organs or in the peritoneal lavage fluid. The capsular tissues
      surrounding the implants contained titanium at levels ranging from 2610 to 16786
      ng/g for unanodized plates, and 888-5933 ng/g for anodized plates. The titanium
      levels within the peritoneal leukocytes of animals with unanodized implants were
      significantly elevated (P = 0.01) over time, as compared with controls. The level
      of titanium in the peritoneal leukocytes of animals with anodized implants was
      not significantly elevated when compared with controls. Titanium levels in the
      trace range, as measured in the capsular tissues, are likely a result of
      corrosion. Surface treatment of titanium by anodization reduces passive
      dissolution.

PMID- 10208409
TI  - Influence of a cellulosic ether carrier on the structure of biphasic calcium
      phosphate ceramic particles in an injectable composite material.
AB  - An injectable composite material based on biphasic calcium phosphate (BCP) and a
      nonionic cellulose ether has been elaborated for use in percutaneous surgery for
      spine fusion. This paper reports the characterization results of this material by
      spectroscopic techniques including X-ray diffraction (XRD), infrared spectroscopy
      (FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy
      (SEM) fitted with an energy dispersive X-Ray analysis system and high-resolution
      transmission electron microscopy (HR-TEM). From FTIR and XPS results, it was
      observed that the adhesion between the polymer and the ceramic might be insured
      by oxygen bridging developed through an ionic bonding between calcium ions and (C
      O) groups of the polymer. Moreover, XPS showed attraction of Ca2+ ions in the
      polymer matrix, while the ceramic surface was modified in a HPO4(2-) -rich layer.
      These results suggest a possible dissolution/precipitation process at the
      interface ceramic/polymer. HR-TEM observations supported this hypothesis, showing
      a light contrasted fringe at the surface of the ceramic grains in the composite
      paste. As well, changes in the XRD spectra could indicate a small decrease in the
      crystal size of the BCP powder through the contact to polymer solution. In
      addition, SEM observation showed a decrease of the initial BCP granulometry.
      Aggregates of 80-200 microm seemed to be mostly dissociated in micrograins. The
      ceramic grains were coated with and bonded between each other by the polymer
      matrix, which acted as spacer in between the ceramic grains, creating a
      macroporous-like material structure.

PMID- 10208411
TI  - Platelet adhesion on a bioresorbable poly(propylene fumarate-co-ethylene glycol)
      copolymer.
AB  - Platelet adhesion and aggregation on poly(propylene fumarate-co-ethylene glycol),
      P(PF-co-EG), hydrogels was examined under both static and flow conditions.
      Adherent platelets were quantified under static conditions using both 111Indium
      oxine-labeled platelets as well as a lactate dehydrogenase, LDH, assay. The
      radiolabeling assay showed a significant decrease in platelet attachment on the
      copolymer hydrogel films relative to the poly(propylene fumarate), PPF,
      homopolymer. In addition, there were reductions in adhesion resulting from the
      increase in poly(ethylene glycol), PEG, weight percent or molecular weight. There
      was good agreement between both assays under static conditions for the copolymer
      films. Platelet surface coverage was quantified under flow conditions in a
      parallel plate flow chamber using the LDH assay. There was a dramatic decrease in
      the number of adherent platelets on the copolymers relative to glass and silicone
      rubber controls. All of the copolymer surfaces showed minimal aggregation with no
      thrombus formation or platelet spreading as assessed qualitatively using scanning
      electron microscopy. These results suggest that P(PF-co-EG) is a good candidate
      for development as a cardiovascular implant.

PMID- 10208412
TI  - Effect of powder grinding on hydroxyapatite formation in a polymeric calcium
      phosphate cement prepared from tetracalcium phosphate and poly(methyl vinyl ether
      maleic acid).
AB  - The primary aim of this study was to determine if cements based on poly(methyl
      vinyl ether-maleic acid) (PMVE-Ma) and tetracalcium phosphate resulted in
      hydroxyapatite formation. In addition, the mechanical strength of this type of
      polymeric calcium phosphate cement was evaluated. Cements were prepared by
      mixing, in a powder/liquid mass ratio of 3.0, an aqueous solution of PMVE-Ma
      (mass fraction = 25%) and tetracalcium phosphate powders ground for various
      periods of time. The tetracalcium phosphate powders and set cements were
      characterized by means of X-ray powder diffraction and scanning electron
      microscopy. Mechanical strengths of the cements were tested 24 h after mixing.
      Prolonged grinding of tetracalcium phosphate powder decreased particle size
      and/or crystallite size and increased lattice distortion. This enhanced the
      reactivity of the tetracalcium phosphate powder and elevated the extent of
      crosslinking between PMVE-Ma molecules, resulting in improved mechanical
      strength. Hydroxyapatite formation was detected in the cement prepared with the
      most finely ground tetracalcium phosphate powder. The conversion of residual
      tetracalcium phosphate particles to more thermodynamically stable hydroxyapatite
      crystals will reduce the solubility of the polymeric cement and increase its
      biocompatibility.

PMID- 10208413
TI  - The Shp-2 tyrosine phosphatase activates the Src tyrosine kinase by a non
      enzymatic mechanism.
AB  - Previously, we demonstrated that the Src tyrosine kinase interacts with the Shp-2
      tyrosine phosphatase. To determine whether Shp-2 regulates Src kinase activity,
      we measured Src activity in cells overexpressing wild-type or catalytically
      inactive C463S Shp-2. We observed a 2-3-fold increase in the specific activity of
      Src in both cell types and the increase did not appear to be due to
      dephosphorylation of Tyr 527 or phosphorylation of Tyr 416 on Src. Conversely, we
      observed a 2-3-fold decrease in the specific activity of Src when Shp-2
      expression was inhibited. Using glutathione S-transferase-fusion proteins, we
      demonstrated that Shp-2 binds to the SH3 domain of Src. Our findings reveal that
      the Shp-2 tyrosine phosphatase can regulate the Src tyrosine kinase by a non
      enzymatic mechanism. We also found that the phosphatase activity of Shp-2
      immunoprecipitates is downregulated in cells transformed by Src or other
      proteins, and that Shp-2 preferentially associates with the membrane fraction of
      transformed cells. We suggest that membrane-association of Shp-2 is important for
      regulating Shp-2 activity.

PMID- 10208414
TI  - p53 mediated death of cells overexpressing MDM2 by an inhibitor of MDM2
      interaction with p53.
AB  - The p53 tumour suppressor is frequently inactivated in human tumours. One form of
      inactivation results from overexpression of MDM2, that normally forms a negative
      auto-regulatory loop with p53 and inhibits its activity through complex
      formation. We have investigated whether disrupting the MDM2-p53 complex in cells
      that overexpress MDM2 is sufficient to trigger p53 mediated cell death. We find
      that expression of a peptide homologue of p53 that binds to MDM2 leads to
      increased p53 levels and transcriptional activity. The consequences are increased
      expression of the downstream effectors MDM2 and p21WAF1/CIP1, inhibition of
      colony formation, cell cycle arrest and cell death. There is also a decrease in
      E2F activity, that might have been due to the known physical and functional
      interactions of MDM2 with E2F1/DP1. However, this decrease is p53 dependent, as
      are also colony formation, cell cycle arrest and cell death. These results show
      that a peptide homologue of p53 is sufficient to induce p53 dependent cell death
      in cells overexpressing MDM2, and support the notion that disruption of the p53
      MDM2 complex is a target for the development of therapeutic agents.

PMID- 10208415
TI  - Centrosome hyperamplification in human cancer: chromosome instability induced by
      p53 mutation and/or Mdm2 overexpression.
AB  - We have previously reported that loss of p53 tumor suppressor protein results in
      centrosome hyperamplification, which leads to aberrant mitosis and chromosome
      instability. Since p53 is either deleted or mutated in human cancers at a high
      frequency, we investigated whether human cancers showed centrosome
      hyperamplification. Screening of advanced stage breast ductal carcinomas and
      squamous cell carcinomas of the head and neck (SCCHN) revealed that centrosome
      hyperamplification is frequent in both tumor types. Moreover, through the
      analyses of p53 in SCCHN samples by direct sequencing and by loss-of
      heterozygosity test, we found that p53 mutations correlated with occurrence of
      centrosome hyperamplification. However, in some cases, we observed centrosome
      hyperamplification in tumors that retained wild-type p53. These tumors contained
      high levels of Mdm2. Since Mdm2 can inactivate p53 through physical association,
      we investigated whether Mdm2 overexpression induced centrosome
      hyperamplification. We found that Mdm2 overexpression, like loss of p53, induced
      centrosome hyperamplification and chromosome instability in cultured cells.

PMID- 10208416
TI  - Regulation of cdc2 gene expression by the upstream stimulatory factors (USFs).
AB  - cdc2 gene expression is under the control of multiple factors. Although E2F/DP
      proteins have been reported to play a central role, they cannot account for all
      aspects of the fine modulation of cdc2 gene expression during cell cycle and
      embryonic development. To characterize the transcription factors that control
      cdc2 gene expression during nerve cell differentiation in avians, we have
      previously cloned the quail cdc2 gene promoter region. We had identified an
      octamer (CAGGTGGC) containing an E-box, which has important activity in
      regulating cdc2 transcription. Using in vivo genomic footprinting experiments, we
      show here that this motif, currently named IG, is the target of binding proteins
      at different stages of neuroretina development, confirming its importance as a
      regulatory response element for cdc2 gene expression. A subset of Helix-Loop
      Helix family of transcription factors, known as Upstream Stimulatory Factors
      (USFs) specifically bind to this sequence as dimers. Moreover, our results
      indicate that USFs transactivate the promoter of cdc2 via the IG motif. These
      data may help to better understand the mechanisms that control cell division in
      differentiating nerve cells.

PMID- 10208417
TI  - Methylation of the BRCA1 promoter region in sporadic breast and ovarian cancer:
      correlation with disease characteristics.
AB  - Reduced expression of BRCA1 has been reported in sporadic breast cancer, although
      the mechanisms underlying this phenomenon remain unclear. Abnormal methylation
      leading to silencing of tumour suppressor genes has been implicated in
      tumorigenesis in a wide range of sporadic cancers. Therefore, we sought to
      determine the frequency of methylation within the BRCA1 promoter region in a
      large group of sporadic invasive breast (n =96) and ovarian (n = 43) carcinomas
      using Southern analyses. Overall, methylation was detected in 11% of breast
      cancer cases and in 5% of ovarian tumours. Methylation of the BRCA1 promoter
      region was strongly correlated with lack of estrogen and progesterone receptor
      expression. It is clear from the frequency of abnormal methylation of the BRCA1
      promoter region, that this cannot be the sole mechanism mediating the reduced
      expression of BRCA1 that has previously been reported to occur in the majority of
      invasive sporadic breast tumours. Nevertheless this study suggests that abnormal
      methylation of the BRCA1 promoter may be important in tumorigenesis in a subset
      of sporadic breast and ovarian cancers.

PMID- 10208418
TI  - Ectopic expression of constitutively activated Ral GTPase inhibits cell shape
      changes during Drosophila eye development.
AB  - The small GTP-binding protein Ral is activated by RalGDS, one of the effector
      molecules for Ras. Active Ral binds to a GTPase activating protein for CDC42 and
      Rac. Although previous studies suggest a role for Ral in the regulation of CDC42
      and Rac, which are involved in arranging the cytoskeleton, its in vivo function
      is largely unknown. To examine the effect of overexpressing Ral on development,
      transgenic Drosophila were generated that overexpress wild-type or mutated Ral
      during eye development. While wild-type Ral caused no developmental defects,
      expression of a constitutively activated protein resulted in a rough eye
      phenotype. Activated Ral did not affect cell fate determination in the larval eye
      discs but caused severe disruption of the ommatidial organization later in pupal
      development. Phalloidin staining showed that activated Ral perturbed the
      cytoskeletal structure and cell shape changes during pupal development. This
      phenotype is similar to that caused by RhoA overexpression. In addition, the
      phenotype was synergistically enhanced by the coexpression of RhoA. These results
      suggest that Ral functions to control the cytoskeletal structure required for
      cell shape changes during Drosophila development.

PMID- 10208420
TI  - Cyclin D1 and D3 associate with the SCF complex and are coordinately elevated in
      breast cancer.
AB  - D-type cyclins are important cell cycle regulators that promote cellular
      proliferation in response to growth factors by inactivation of the retinoblastoma
      protein (Rb). Cyclin D1 has been shown to be overexpressed in several cancer
      types and to act as an oncogene in breast cancers. As D-type cyclins are rate
      limiting for progression into S phase, the level at which they accumulate must be
      carefully regulated. Several mechanisms leading to overexpression of cyclin D1
      have been reported including amplification, translocation and stabilization of
      the mRNA. Here, we present data showing elevated cyclin D1 protein in breast
      cancer samples in the absence of elevated mRNA level. Further, we found that in
      these cases, cyclin D3 protein also accumulates and that the coordinate increase
      in cyclin D1 and D3 occurs in 15% (7/47) of breast cancers. In addition we show
      that blocking the activity of the 26S proteosome results in the accumulation of
      cyclin D1 and D3, that both D-type cyclins are ubiquitinated and associate with
      Cul-1, a component of the SCF ubiquitin ligase complex. Finally, we show that the
      coordinated elevation of cyclin D1 and D3 is also observed in the breast cell
      line MCF-7 and demonstrate that the degradation of cyclin D1 and D3 is deficient
      in this cell line. These results indicate that cyclin D1 and cyclin D3 share a
      common mechanism of degradation and we propose that the coordinate increase of D
      type cyclins observed in primary breast cancers reflects a defect in their
      proteolysis.

PMID- 10208419
TI  - Rho-dependent and -independent tyrosine phosphorylation of focal adhesion kinase,
      paxillin and p130Cas mediated by Ret kinase.
AB  - Glial cell line-derived neurotrophic factor (GDNF) signals through a unique
      receptor system that includes Ret receptor tyrosine kinase and a glycosyl
      phosphatidylinositol-linked cell surface protein. In the present study, we have
      identified several proteins in neuroblastoma cells that are phosphorylated on
      tyrosine in response to GDNF. The phosphorylated proteins include focal adhesion
      kinase (FAK), paxillin and Crk-associated substrate, p130Cas, all of which are
      known to be associated with focal adhesions. Of these, paxillin and p130Cas
      interacted with Crk proteins in GDNF-treated neuroblastoma cells. GDNF also
      induced reorganization of the actin cytoskelton. Tyrosine phosphorylation of FAK,
      paxillin and p130Cas was inhibited by cytochalasin D or two specific inhibitors
      of phosphatidylinositol-3' kinase (PI-3' kinase), wortmannin and LY294002,
      indicating that their tyrosine phosphorylation depends on the formation of actin
      stress fiber and activation of PI-3' kinase. In addition, phosphorylation of FAK
      but not of paxillin and p130Cas was markedly impaired by the Clostridium
      botulinum C3 exoenzyme that specifically ADP-ribosylates and inactivates Rho.
      These results suggested the presence of Rho-dependent and -independent signaling
      pathways downstream of PI-3' kinase that mediate tyrosine phosphorylation of FAK,
      paxillin and p130Cas through Ret kinase.

PMID- 10208421
TI  - Enforced expression of HOXB7 promotes hematopoietic stem cell proliferation and
      myeloid-restricted progenitor differentiation.
AB  - Hematopoietic progenitor/stem cells (HPCs/HSCs) purified from human adult
      peripheral blood (PB) were triggered into cycling, retrovirally transduced with
      HOXB7 and then functionally assayed in vitro. HPCs were assayed in multi- and
      unilineage differentiation cultures in either liquid phase or semisolid medium,
      primitive HPCs in the high proliferative potential colony-forming cell (HPP-CFC)
      evaluation system and putative HSCs in Dexter type long-term culture (LTC) as LTC
      initiating cells (LTC-ICs). Control experiments ensured that the exogenous HOXB7
      gene was constantly expressed, while the endogenous one was barely or not
      transcribed. Enforced expression of the gene markedly modulated the
      proliferation/differentiation program of the entire HSC/HPC population. Enforced
      HOXB7 expression exerted a potent stimulatory effect on the proliferation of the
      primitive HPC and putative HSC subsets, assayed as HPP-CFCs and LTC-ICs
      respectively. While not modifying the total number of HPCs, exogenous HOXB7
      induced an increase of the number of granulo-monocytic (GM) HPCs [colony-forming
      unit GM (CFU-GM) CFU-GM, CFU-G and CFU-M, as evaluated by clonogenic assays] and
      markedly amplified the progeny of both CFU-G and CFU-M, which showed a sustained
      proliferation through at least 1-2 months (as evaluated in liquid suspension
      culture). The prolonged proliferative stimulus induced by HOXB7 transfer into
      LTC, primitive and GM oriented HPC culture was characterized by persistent
      proliferation of a discrete population of blast cells and a large pool of
      differentiated myeloid precursors. Altogether, these results suggest the
      hypothesis that the proliferative stimulus exerted by exogenous HOXB7 in
      primitive and GM-oriented HPCs may represent a preleukemic immortalization step.
      Consistent with the functional role of HOXB7 in the initial ontogenetic phase,
      these studies indicate that ectopic HOXB7 expression in early HPCs and HSCs from
      adult PB stimulates their self renewal, sustained proliferation and myeloid
      differentiation.

PMID- 10208422
TI  - Transcriptional repression of the E2F-1 gene by interferon-alpha is mediated
      through induction of E2F-4/pRB and E2F-4/p130 complexes.
AB  - E2F is a heterodimeric transcription factor composed of one of five E2F subunits
      (E2F-1 to E2F-5) and a DP subunit. E2F regulates the expression of several growth
      promoting genes, and thus, can be a target of antiproliferative action of
      interferons (IFNs). In this study, we investigated the mechanisms whereby IFN
      alpha suppresses transcription of the E2F-1 gene. Transfection studies revealed
      that E2F-1 promoter was functionally divided into two parts: upstream activation
      sequences (UAS) and a downstream negative-regulatory element (E2F-binding sites).
      When cells were proliferating, transcription of the E2F-1 gene was primarily
      driven by the UAS, while E2F sites were not involved in activation. IFN-alpha
      markedly reduced E2F-1 promoter activity, but introduction of non-binding
      mutation at the E2F sites completely abrogated the inhibition. Free E2F4 was
      found to be the predominant species bound to the E2F sites in proliferating
      cells. IFN-alpha induced upregulation of E2F-4 along with dephosphorylation of
      pRB and p130, which resulted in the formation of E2F-4/pRB and E2F-4/p130
      complexes on the E2F-1 promoter. These complexes function as transcriptional
      repressors to inhibit E2F-1 mRNA expression. Our findings indicate that E2F-4 is
      a critical regulator of E2F-1, which offer an excellent paradigm for
      understanding functional diversity within the E2F family.

PMID- 10208423
TI  - Refined mapping of the region of loss of heterozygosity on the long arm of
      chromosome 7 in human breast cancer defines the location of a second tumor
      suppressor gene at 7q22 in the region of the CUTL1 gene.
AB  - In breast cancer, loss of heterozygosity (LOH) has been described on the long arm
      of chromosome 7, at band q31, suggesting the presence of a tumor suppressor gene
      in this region. In this study, we have identified a second region of LOH on 7q,
      at band 7q22. Deletion of genetic material at 7q22 was found in all tumor types
      and grades and was associated with increased tumor size. The region of LOH at
      7q22 in every case included one or more of three polymorphic markers that are
      located within the CUTL1 gene. LOH of 7q22 has also been documented in the case
      of human uterine leiomyomas (Zeng et al., 1997; Ishwad et al., 1997).
      Interestingly, in both leiomyomas and mammary tumors induced in transgenic mice
      expressing the Polyomavirus (PyV) large T (LT) antigen, immunocomplexes of CUTL1
      and PyV LT antigen were detected (Webster et al., 1998). Altogether, genetic data
      in human breast cancer and biochemical analyses in breast tumors from transgenic
      mice suggest that CUTL1 is a candidate tumor suppressor gene.

PMID- 10208424
TI  - The SV40 large T oncoprotein disrupts DNA-binding of the cell cycle-regulated
      transcriptional repressor CDF.
AB  - A hallmark of neoplastic transformation by DNA tumor viruses is the deregulation
      of cell cycle genes. At least in some genes, this deregulation appears to be due
      to the oncoprotein-mediated disruption of complexes between E2F and pocket
      proteins and the ensuing generation of transcriptionally active free E2F. In the
      present study, we have analysed the effect of the SV40 large T oncoprotein (SV
      LT) on the function of a different cell cycle-regulated transcriptional
      repressor, CDF, which is the principal regulator of the cdc25C, cyclin A and cdc2
      genes. As shown by genomic footprinting of sorted G1 and G2 cell populations,
      transformation by SV-LT completely abrogated protection of the CDF binding site
      (CDE-CHR) in the cdc25C promoter. In agreement with this observation, expression
      of the SV-LT in fibroblasts led to a dramatic up-regulation of the cdc25C
      promoter in cells synchronized in G0. These findings indicate that the
      oncoprotein-mediated dissociation of the CDF repressor protein from its cognate
      DNA-binding site is a major mechanism in virus-induced transcriptional
      deregulation.

PMID- 10208425
TI  - Suppression of src-induced transformed phenotype by expression of tropomyosin-1.
AB  - Suppression of high M(r) tropomyosins (TMs) is a common feature of transformed
      cells. Previous work from this laboratory has demonstrated that the isoform 1 of
      TM, TM1, acts as an anti-oncogene in ras-transformed murine fibroblasts. In this
      study, we have investigated whether TM1 is a ras-specific suppressor, or a
      general suppressor protein of the cellular transformation. V-src transformed
      fibroblasts, which express decreased TM1, were transduced with a full-length cDNA
      to overexpress TM1. Both the control and the transduced cells expressed v-src
      kinase at comparable levels. TM1 expressing (src-T1) cells grew at a lower rate
      in monolayer, exhibited well spread, flat morphology than the control cells.
      Enhanced expression of TM1 resulted in improved microfilamental architecture.
      More significantly, src-T1 cells completely failed to grow under anchorage
      independent conditions. These data demonstrate that TM1 is as an anti-oncogene of
      functionally diverse oncogenes, and it is a class II tumor suppressor protein.

PMID- 10208427
TI  - Isoform-specific insertion near the Grb2-binding domain modulates the intrinsic
      guanine nucleotide exchange activity of hSos1.
AB  - Two human hSos1 isoforms (Isf I and Isf II; Rojas et al., Oncogene 12, 2291-2300,
      1996) defined by the presence of a distinct 15 amino acid stretch in one of them,
      were compared biologically and biochemically using representative NIH3T3
      transfectants overexpressing either one. We showed that hSos1-Isf II is
      significantly more effective than hSos1-Isf I to induce proliferation or
      malignant transformation of rodent fibroblasts when transfected alone or in
      conjunction with normal H-Ras (Gly12). The hSos1-Isf II-Ras cotransfectants
      consistently exhibited higher saturation density, lower cell-doubling times,
      increased focus-forming activity and higher ability to grow on semisolid medium
      and at low serum concentration than their hSos1-Isf I-Ras counterparts.
      Furthermore, the ratio of GTP/GDP bound to cellular p21ras was consistently
      higher in the hSos1-Isf II-transfected clones, both under basal and stimulated
      conditions. However, no significant differences were detected in vivo between Isf
      I- and Isf II-transfected clones regarding the amount, stability and subcellular
      localization of Sos1-Grb2 complex, or the level of hSos1 phosphorylation upon
      cellular stimulation. Interestingly, direct Ras guanine nucleotide exchange
      activity assays in cellular lysates showed that Isf II transfectants consistently
      exhibited about threefold higher activity than Isf I transfectants under basal,
      unstimulated conditions. Microinjection into Xenopus oocytes of purified peptides
      corresponding to the C-terminal region of both isoforms (encompassing the 15
      amino acid insertion area and the first Grb2-binding motif) showed that only the
      Isf II peptide, but not its corresponding Isf I peptide, was able to induce
      measurable rates of meiotic maturation, and synergyzed with insulin, but not
      progesterone, in induction of GVBD. Our results suggest that the increased
      biological potency displayed by hSos1-Isf II is due to higher intrinsic guanine
      nucleotide exchange activity conferred upon this isoform by the 15 a.a. insertion
      located in proximity to its Grb2 binding region.

PMID- 10208426
TI  - Cross-talk between the Smad1 and Ras/MEK signaling pathways for TGFbeta.
AB  - Our previous data demonstrated that Ras activation was necessary and sufficient
      for transforming growth factor-beta (TGFbeta)-mediated Erk1 activation, and was
      required for TGFbeta up-regulation of the Cdk inhibitors (CKI's) p27(Kip1) and
      p21(Cip1) (KM Mulder and SL Morris, J. Biol. Chem., 267, 5029-5031, 1992; MT
      Hartsough and KM Mulder, J. Biol. Chem., 270, 7117-7124, 1995; MT Hartsough et
      al., J. Biol. Chem., 271, 22368-22375, 1996 and J Yue et al., Oncogene, 17, 47
      55, 1998). Here we examined the role of Ras in TGFbeta-mediated effects on a rat
      homolog of Smad1 (termed RSmad1). We demonstrate that both TGFbeta and bone
      morphogenetic protein (BMP) can induce endogenous Smad1 phosphorylation in
      intestinal epithelial cells (IECs). The combination of transient expression of
      RSmad1 and TGFbeta treatment had an additive effect on induction of the TGFbeta
      responsive reporter 3TP-lux. Either inactivation of Ras by stable, inducible
      expression of a dominant-negative mutant of Ras (RasN17) or addition of MAP and
      ERK kinase (MEK) inhibitor PD98059 to cells significantly decreased the ability
      of both TGFbeta and BMP to induce phosphorylation of endogenous Smad1 in IECs.
      Moreover, either inactivation of Ras or addition of PD98059 to IEC 4-1 cells
      inhibited the ability of RSmad1 to regulate 3TP luciferase activity in both the
      presence and absence of TGFbeta. Collectively, our data indicate that TGFbeta can
      regulate RSmad1 function in epithelial cells, and that the Ras/MEK pathway is
      partially required for TGFbeta-mediated regulation of RSmad1.

PMID- 10208428
TI  - Comparison of the effectiveness of adenovirus vectors expressing cyclin kinase
      inhibitors p16INK4A, p18INK4C, p19INK4D, p21(WAF1/CIP1) and p27KIP1 in inducing
      cell cycle arrest, apoptosis and inhibition of tumorigenicity.
AB  - Cell cycle regulatory proteins are important candidates for therapeutic tumour
      suppressors. Adenovirus vectors were constructed to overexpress cyclin kinase
      inhibitors p16INK4A, p18INK4C, p19INK4D, p21(WAF1/CIP1) and p27KIP1 under the
      control of the murine cytomegalovirus immediate early gene promoter. These
      vectors directed the efficient expression of each of the cyclin kinase inhibitors
      and induced growth arrest, inhibited DNA synthesis, and prevented phosphorylation
      of the retinoblastoma protein (pRb) in cell lines expressing functional pRb. In
      pRb-deficient cells, expression of the cyclin kinase inhibitors was not effective
      in inhibiting DNA replication or growth arrest. Interestingly, three of the
      cyclin kinase inhibitors, p16, p18 and p27 were found to induce apoptotic death
      in transduced HeLa and A549 cells. When the vectors were tested for their ability
      to inhibit tumorigenicity in a polyomavirus middle T antigen model of murine
      breast carcinoma, expression of the cyclin kinase inhibitors resulted in a delay
      in tumour formation that varied from several weeks for the p19 expressing vector
      to greater than 25 weeks for the p27 expressing vector. When tumours were
      injected directly with the adenovirus vectors expressing the cyclin kinase
      inhibitors, only treatment with the vector expressing p16 resulted in a delay in
      tumour growth.

PMID- 10208429
TI  - The translation initiation factor, hu-Sui1 may be a target of hepatitis B X
      antigen in hepatocarcinogenesis.
AB  - The role of hepatitis B virus X antigen in the development of hepatocellular
      carcinoma was explored by stably transfecting HepG2 cells with an X antigen
      expression vector, and identifying the differences in gene expression that
      distinguish X positive from X negative cells by subtractive PCR. One
      differentially expressed gene, the human homolog of sui1 (hu-sui1), encodes a
      translation initiation factor whose expression was suppressed by X antigen in
      HepG2 cells. Hu-Sui1 was also expressed in nontumor liver but not in tumor cells
      from patients with hepatocellular carcinoma. Introduction of hu-sui1 into HepG2
      cells inhibited cell growth in culture, in soft agar, and partially inhibited
      tumor formation in nude mice. Hence, the suppression of hu-sui1 by X antigen may
      result in the abrogation of negative growth regulation and contribute to the
      development of hepatocellular carcinoma.

PMID- 10208430
TI  - hRAD17, a structural homolog of the Schizosaccharomyces pombe RAD17 cell cycle
      checkpoint gene, stimulates p53 accumulation.
AB  - The RAD17 gene product of S. Pombe is an essential component of the checkpoint
      control pathway which responds to both DNA damage and disruption of replication.
      We have identified a human cDNA that encodes a polypeptide which is structurally
      conserved with the S. Pombe Rad17 protein. The human gene, designated hRAD17,
      predicts an encoded protein of 590 amino acids and a molecular weight of 69 kD.
      Amino acid sequence alignment revealed that hRadl7 has 28.3% and 52.5% similarity
      with the S. Pombe Rad17 protein, and 21.8% identity and 45.8% similarity to the
      budding yeast cell cycle checkpoint protein, Rad 24. When introduced into the S.
      Pombe rad17 mutant, hRAD17 was able to partially revert its hydroxyurea and
      ionizing radiation hypersensitivity, but not its UV hypersensitivity. Permanent
      overexpression of the hRAD17 gene in human fibrosarcoma cells resulted in p53
      activation and a significant reduction of S- and G2/M-phase cells accompanied by
      an accumulation of the G1-phase population, suggesting that hRAD17 may have a
      role in cell cycle checkpoint control. Immunostaining of HT-1080 cells
      transiently transfected with a hRAD17 construct confirmed the nuclear
      accumulation of p53, which mimics the induction caused by DNA damage. Using FISH
      analysis, we have mapped the hRAD17 locus to human chromosome 5q11.2.

PMID- 10208431
TI  - The t(8;21) fusion protein, AML1/ETO, transforms NIH3T3 cells and activates AP-1.
AB  - The 8;21 translocation is the most common cytogenetic abnormality in human acute
      myelogenous leukemia, joining the AML1 gene on chromosome 21, to the ETO gene on
      chromosome 8, forming the AML1/ETO fusion gene. The AMLI/ETO fusion protein has
      been shown to function mainly as a transcriptional repressor of AML1 target genes
      and to block AML1 function in vitro and in vivo. However, AML1/ETO can also
      activate the BCL-2 promoter and cause enhanced hematopoietic progenitor self
      renewal in vitro, suggesting gain-of-functions unique to the fusion protein. We
      used NIH3T3 cells to determine the transforming capacity of AML1/ETO, and to
      further characterize its mechanism of action. Expression of AML1/ETO in NIH3T3
      cells caused cell-type specific cell death, and cellular transformation,
      characterized by phenotypic changes, anchorage-independent growth, and tumor
      formation in nude mice. In contrast, neither expression of AML1A, AML1B or ETO
      altered the normal growth pattern of the cells. To investigate the mechanism of
      transformation by AML1/ETO, we analysed the levels of activated, phosphorylated c
      Jun (ser63) and other constituents of the AP-1 complex, in the presence of
      various AML1/ETO related proteins. Expression of AML1/ETO increased the level of
      c-Jun-P (ser63), and activated AP-1 dependent transcription, which was inhibited
      by expression of a dominant-negative c-Jun protein. Mutational analysis revealed
      that the runt homology domain (RHD) and a C-terminal transcriptional repression
      domain in AML1/ETO are required for transformation, activation of c-Jun and
      increased AP-1 activity. These results establish the transforming potential of
      the t(8;21) fusion protein and link this gain-of-function property to modulation
      of AP-1 activity.

PMID- 10208432
TI  - Suppression of metastasis formation by a recombinant single chain antibody-toxin
      targeted to full-length and oncogenic variant EGF receptors.
AB  - Cytotoxic strategies which are directed to tumor-associated antigens might be
      most beneficial for cancer patients with minimal tumor load such as in an
      adjuvant setting after initial therapy. We have recently described a highly
      potent single chain antibody-toxin, scFv(14E1)-ETA, which consists of the
      variable domains of the antibody 14E1 genetically fused to a truncated form of
      Pseudomonas exotoxin A. ScFv(14E1)-ETA specifically recognizes the human
      epidermal growth factor receptor (EGFR) and the oncogenically activated receptor
      variant EGFRvIII, which have been implicated in the development of various human
      malignancies. Here we have investigated the antimetastatic activity of
      bacterially expressed scFv(14E1)-ETA and its disulfide-stabilized derivative ds
      scFv(14E1)-ETA in a novel model for disseminated disease which is based on murine
      renal carcinoma cells subsequently transfected with the E. coli beta
      galactosidase gene, and human full-length or variant EGFR cDNAs. Intravenous
      injection of these Renca-lacZ/EGFR and Renca-lacZ/EGFRvIII cells in syngenic
      Balb/c mice led to the formation of pulmonary metastases which were readily
      detectable upon excision of the lungs and X-gal staining. Systemic treatment of
      mice with scFv(14E1)-ETA resulted in the complete suppression of Renca
      lacZ/EGFRvIII metastasis formation and drastically reduced the number of
      pulmonary Renca-lacZ/EGFR tumor nodules. The ds-scFv(14E1)-ETA derivative where
      the antibody variable regions are connected by an artificial disulfide bond
      displayed improved thermal stability at physiological temperature but due to
      reduced cytotoxic activity was less potent than the original scFv(14E1)-ETA in
      metastasis suppression.

PMID- 10208433
TI  - DNA damage induced p53 stabilization: no indication for an involvement of p53
      phosphorylation.
AB  - Abundance and activity of p53 are predominantly regulated posttranslationally.
      Structural disturbance in transcribed genes induced by radiation, e.g. DNA
      damage, or by transcriptional inhibitors cause p53 protein stabilization by a yet
      unknown mechanism. Using stable and transient transfections for the analysis of
      p53 mutant proteins, we have ruled out a role in stabilization by UV, gamma
      irradiation or actinomycin C for the following putative phosphorylation sites in
      the p53 protein: serines 6, 9, 15, 33, 315 and 392, and threonine 18. By double
      mutation combinations of phosphorylations were also ruled out; 6,9; 15,18; 15,37.
      These mutations eliminate modifications by casein kinases I and II, DNA-PK, ATM,
      CDK and JNK. Also the 30 carboxyterminal amino acids are not required for induced
      p53 stabilization. Thus neither phosphorylations of individual amino acids nor
      interactions of the carboxyterminus of p53 with cellular macromolecules appear to
      play a role in the stabilization process. The only single prerequisite for
      induced stabilization of p53 is its prior destabilization by Mdm2. However, the
      level of active Mdm2 must be controlled carefully: overexpression of Mdm2
      inhibits UV induced p53 stabilization.

PMID- 10208434
TI  - Attenuated expression of the serum responsive T1 gene in ras transformed
      fibroblasts due to the inhibition of c-fos gene activity.
AB  - The T1 gene encodes a protein, which shares homology with the IL-1 receptors. In
      fibroblasts, T1 is induced by growth factors and in response to the onset of
      oncogene expression. The c-fos gene is transiently activated in these situations
      and was shown to be the major mediator of T1 gene induction. In contrast, the
      sustained expression of a ras oncogene in NIH3T3 cells resulted in the
      downregulation of basal T1 gene activity and the attenuation of T1 gene induction
      in response to mitogenic signals. Likewise, the immediate early genes encoding c
      Fos, FosB, and Fra-2 are repressed in these cells. T1 gene repression could be
      overcome by the forced expression of c-fos in ras transformed fibroblasts. Thus,
      the lack of c-fos gene expression is the likely cause for ras mediated T1 gene
      repression. Fra-1, in contrast to the other three members of the Fos family, is
      permanently synthesized in high amounts in ras transformed NIH3T3 fibroblasts. We
      show that AP-1, which is abundant in these cells throughout the whole cell cycle,
      consists predominantly of Fra-1/c-Jun and Fra1/JunD heterodimers. We provide
      evidence that Fra1/c-Jun heterodimers are responsible for the repression of c-fos
      gene induction following serum stimulation. The introduction of a dominant
      negative version of c-Jun into ras transformed fibroblasts was able to rescue c
      fos gene induction in response to serum stimulation, further demonstrating that
      AP-1 is indeed involved in c-fos gene repression. We conclude that oncogenic ras
      mediates the activation of the fra-1 gene which results in elevated AP-1 activity
      throughout the cell cycle. Fra-1 containing AP-1 complexes repress the c-fos and
      possibly other immediate early genes thereby preventing the induction of certain
      delayed early genes such as the T1 gene in response to mitogenic stimulation.

PMID- 10208435
TI  - Deregulation of the proto-oncogene c-myc through t(8;22) translocation in
      Burkitt's lymphoma.
AB  - In Burkitt's lymphoma (BL) cells the proto-oncogene c-myc is juxtaposed to one of
      the immunoglobulin (Ig) loci on chromosomes 2, 14, or 22. The c-myc gene becomes
      transcriptionally activated as a consequence of the chromosomal translocation and
      shows preferential usage of promoter P1 over P2, a phenomenon referred to as
      promoter shift. In order to define the responsible regulatory elements within the
      Ig lambda locus, we studied the effect of the human Ig lambda enhancer (HuE
      lambda) on c-myc expression after stable transfection into BL cells. A 12 kb
      genomic fragment encompassing HuE lambda, but not HuE lambda alone, strongly
      activated c-myc expression and induced the promoter shift. To identify additional
      elements involved in c-myc deregulation, we mapped DNaseI hypersensitive sites
      within the 12 kb lambda fragment on the construct. Besides one hypersensitive
      site corresponding to HuE lambda, three additional sites were detected. Two of
      these elements displayed enhancer activity after transient transfection. The
      third element did not activate c-myc transcription, but was required for full c
      myc activation and promoter shift. Deletion analyses of the c-myc promoter
      identified the immediate promoter region as sufficient for activation by the Ig
      lambda. locus, but also revealed that induction of the promoter shift requires
      additional upstream elements.

PMID- 10208437
TI  - Transcriptional analysis of the PTEN/MMAC1 pseudogene, psiPTEN.
AB  - PTEN/MMAC1 is a recently characterized tumor suppressor. A pseudogene derived
      from the human PTEN/MMAC1 phosphatase, psiPTEN, has been reported. Recent
      analysis of the pseudogene revealed conflicting results about the expression of
      psiPTEN. In this study, we show that the PTEN/MMAC1 pseudogene is actively
      transcribed in all cells and tissues examined. In some cases, pseudogene
      transcripts were found to represent as much as 70% of the total PTEN/MMAC1 RNA.
      As psiPTEN is transcribed, there is a potential for misinterpretation of
      PTEN/MMAC1 mutations when RT-PCR techniques are used, as well as potential for a
      psiPTEN-encoded translation product. Although we were unable to detect a
      pseudogene protein product in the cell lines examined, a baculovirus produced GST
      pseudogene fusion protein exhibited phosphatase activity comparable to wild type.
      The results of this study, taken together, indicate the potential complication of
      PTEN/MMAC1 molecular analysis caused by the expression of psiPTEN.

PMID- 10208436
TI  - Synergistic effects of retinoic acid and 8-Cl-cAMP on apoptosis require caspase-3
      activation in human ovarian cancer cells.
AB  - We investigated the intracellular mechanisms of retinoic acid (9-cis-RA, 13-cis
      RA or all-trans-RA) and a cyclic AMP analog 8-Cl-cAMP on growth-inhibition and
      apoptosis in human ovarian cancer NIH: OVCAR-3 and OVCAR-8 cells. The cyclic AMP
      analog, 8-Cl-cAMP, acted synergistically with RA in inducing and activating
      retinoic acid receptor beta (RARbeta) which correlated with the growth
      inhibition, cell cycle arrest, and apoptosis in both cell types. In addition,
      combined treatment of cells with RA plus 8-Cl-cAMP resulted in the release of
      cytochrome c, loss in mitochondrial membrane potential and activation of caspase
      3 followed by cleavage of anti-poly(ADP-ribose)polymerase and DNA-dependent
      protein kinase (catalytic subunit). Interestingly, inhibition of caspase-3
      activation blocked RA plus 8-Cl-cAMP induced apoptosis. Furthermore, mutations in
      a CRE-related motif within the RARbeta promoter resulted in loss of both
      transcriptional activation of RARbeta and synergy between RA and 8-Cl-cAMP. Thus,
      RARbeta can mediate RA and/or cyclic AMP action in ovarian cancer cells by
      promoting apoptosis. Loss of RARbeta expression, therefore, may contribute to the
      tumorigenicity of human ovarian cancer cells. These findings suggest that RA and
      8-Cl-cAMP act in a synergistic fashion in inducing apoptosis via caspase-3
      activation, and may have potential for combination biotherapy for the treatment
      of malignant disease such as ovarian cancer.

PMID- 10208438
TI  - Increased E1AF expression in mouse fibrosarcoma promotes metastasis through
      induction of MT1-MMP expression.
AB  - In this study, we investigated the role of E1AF, a member of ets family
      transcription factor, in the acquisition of metastatic capacity by non-metastatic
      mouse fibrosarcoma cell clone, QR-32. The QR-32 cell clone grows progressively
      after co-implantation with gelatin sponge in syngeneic C57BL/6 mice. The cell
      lines (QRsP) established from arising tumors after the co-implantation exhibited
      enhanced tumorigenicity and pulmonary metastasis in vivo as compared with parent
      QR-32 cells. The enhanced pulmonary metastasis of QRsP cells was correlated well
      with augmented production of matrix metalloproteinase-2 (MMP-2) and increased
      expression of membrane-type 1-MMP (MT1-MMP). The QRsP cells also acquired higher
      chemokinetic activities to fibronectin and higher invasive activities through a
      reconstituted basement membrane. Furthermore we observed the elevated mRNA
      expression of E1AF in QRsP cells compared to parent QR-32 cells. Therefore, we
      transfected QR-32 cells with E1AF cDNA. Overexpression of E1AF in the QR-32 cells
      resulted in the induction of MT1-MMP expression and converting an exogenously
      added precursor MMP-2 into active form. E1AF transfectants exhibited more motile
      and invasive activities, and moderately increased pulmonary metastatic activities
      than parental QR-32 cells in vivo, although their metastatic activities were
      lower than those of QRsP cells. These findings suggest that the increased
      expression of E1AF in fibrosarcoma contributes to invasive phenotypes including
      MT1-MMP expression and enhanced cell migration, but not sufficient for exhibiting
      highly metastatic activity in vivo.

PMID- 10208439
TI  - Somatic mutation of the Peutz-Jeghers syndrome gene, LKB1/STK11, in malignant
      melanoma.
AB  - Mutations in LKB1/STK11, a gene mapping to chromosome 19p13.3 and encoding a
      widely expressed serine/threonine kinase, were recently identified as the cause
      of Peutz-Jeghers syndrome. Despite the hamartomatous polyps and increased cancer
      risk associated with this syndrome, somatic alterations in LKB1/STK11 have not
      been identified in human tumours. Prompted by another feature of the syndrome,
      lentigines of the lips and oral mucosa, we evaluated the status of LKB1/STK11
      expression, deletion, and mutation in cell lines and tumour samples from 35
      patients with sporadic malignant melanoma. Two somatic mutations were identified,
      a nonsense mutation (Glu170Stop) causing exon skipping and intron retention, and
      a missense mutation (Asp194Tyr) affecting an invariant residue in the catalytic
      subunit of LKB1/STK11. Our data suggest that LKB1/STK11 may contribute to
      tumorigenesis in a small fraction of malignant melanomas.

PMID- 10208440
TI  - The preeminent role of early untoward experience on vulnerability to major
      psychiatric disorders: the nature-nurture controversy revisited and soon to be
      resolved.

PMID- 10208441
TI  - Cytokines in affective disorders and schizophrenia: new clinical and genetic
      findings.

PMID- 10208442
TI  - Control of transcription and neurological diseases.

PMID- 10208443
TI  - Allelic association of the MTHFR gene with schizophrenia.

PMID- 10208444
TI  - Anti-bipolar therapy: mechanism of action of lithium.
AB  - This review introduces the concepts that multiple actions of lithium are critical
      for its therapeutic effect, and that these complex effects stabilize neuronal
      activities, support neural plasticity, and provide neuroprotection. Three
      interacting systems appear most critical. (i) Modulation of neurotransmitters by
      lithium likely readjusts balances between excitatory and inhibitory activities,
      and decreased glutamatergic activity may contribute to neuroprotection. (ii)
      Lithium modulates signals impacting on the cytoskeleton, a dynamic system
      contributing to neural plasticity, at multiple levels, including glycogen
      synthase kinase-3beta, cyclic AMP-dependent kinase, and protein kinase C, which
      may be critical for the neural plasticity involved in mood recovery and
      stabilization. (iii) Lithium adjusts signaling activities regulating second
      messengers, transcription factors, and gene expression. The outcome of these
      effects appears likely to result in limiting the magnitudes of fluctuations in
      activities, contributing to a stabilizing influence induced by lithium, and
      neuroprotective effects may be derived from its modulation of gene expression.

PMID- 10208445
TI  - Susceptibility genes for nicotine dependence: a genome scan and followup in an
      independent sample suggest that regions on chromosomes 2, 4, 10, 16, 17 and 18
      merit further study.
AB  - Cigarette smoking is associated with considerable morbidity, mortality, and
      public health costs. Genetic factors influence both smoking initiation and
      nicotine dependence, but none of the genes involved have been identified. A
      genome scan using 451 markers was conducted to identify chromosomal regions
      linked to nicotine dependence in a collection of 130 families containing 343
      genotyped individuals (308 nicotine-dependent) from Christchurch, New Zealand. By
      pairwise analysis, the best result was with marker D2S1326 which gave a lod score
      under heterogeneity (H-LOD) of 2.63 (P=0.0012) and a nonparametric linkage (NPL,
      Zall) score of 2.65 (P=0.0011). To identify regions that warranted further study,
      rather than comparing the pairwise scores from the scan to theoretical
      thresholds, we compared them to an empirical baseline, found here to be H-LOD
      scores of 0.5 and Zall scores of 1.0. We also found a number of large (31-88 cM)
      regions where many (8-16) consecutive markers yielded small but positive Zall
      scores. Selected regions of chromosomes 2, 4, 10, 16, 17 and 18 were investigated
      further by additional genotyping of the Christchurch sample and an independent
      sample from Richmond, Virginia (91 families with 264 genotyped individuals, 211
      nicotine-dependent). Multipoint nonparametric analysis showed the following
      maximums for the Christchurch sample: Chr. 2 (Zlr=2.61, P=0.005), Chr. 4
      (Zlr=1.36, P=0.09), Chr. 10 (Zlr=2.43, P=0.008), Chr. 16 (Zlr=0.85, P=0.19), Chr.
      17 (Zlr=1.64, P=0.05), Chr. 18 (Zlr=1.54, P=0.06). Analysis of the Richmond
      sample showed the following maximums: Chr. 2 (Zlr=1.00, P=0.15), Chr. 4
      (Zlr=0.39, P=0.34), Chr. 10 (Zlr=1.21, P=0.11), Chr. 16 (Zlr=1.11, P=0.13), Chr.
      17 (Zlr=1.60, P=0.05), Chr. 18 (Zlr=1.33, P=0.09). It is probable that the small
      samples used here provided only limited power to detect linkage. It may have been
      difficult therefore to detect genes of small effect, or those that are
      influencing risk in only a small proportion of the families. When simply judged
      against the usual standards of linkage significance, none of the individual
      regions yielded strong evidence in either sample. Some or all of the most
      positive results in the genome scan of the Christchurch sample, therefore, could
      be due to chance. However, the presence in the Christchurch scan of multiple
      large regions containing many consecutive positive markers, coupled with the
      relatively positive results in these same regions in the Richmond sample,
      suggests that some of these regions may contain genes influencing nicotine
      dependence and therefore deserve further study.

PMID- 10208446
TI  - Defective corticogenesis and reduction in Reelin immunoreactivity in cortex and
      hippocampus of prenatally infected neonatal mice.
AB  - Recent reports indicate an association between second trimester human influenza
      viral infection and later development of schizophrenia. Postmortem human brain
      studies also provide evidence for reduction in Reelin mRNA (an important
      secretory protein responsible for normal lamination of the brain) in
      schizophrenic brains. We hypothesized that human influenza infection in day 9
      pregnant mice would alter the expression of reelin in day 0 neonatal brains.
      Prenatally-infected murine brains from postnatal day 0 showed significant
      reductions in reelin-positive cell counts in layer I of neocortex and other
      cortical and hippocampal layers when compared to controls. Whereas layer I Cajal
      Retzius cells produced significantly less Reelin in infected animals, the same
      cells showed normal production of calretinin and nNOS when compared to control
      brains. Moreover, prenatal viral infection caused decreases in neocortical and
      hippocampal thickness. These results implicate a potential role of prenatal viral
      infection in causation of neuronal migration abnormalities via reduction in
      Reelin production in neonatal brains.

PMID- 10208447
TI  - Polymorphisms of the human homologue of the Drosophila white gene are associated
      with mood and panic disorders.
AB  - The Drosophila white gene is a member of the ATP-binding cassette (ABC)
      transporter superfamily and is involved in the cellular uptake of tryptophan. Its
      human homologue gene (hW) has been mapped to chromosome 21q22.3. Tryptophan is
      the precursor for the neurotransmitter serotonin, which has been implicated in
      the regulation of mood and anxiety. The locus 21q22.3 has also been reported to
      be associated with mood disorders. The 3'-untranslated region (3'-UTR) in the hW
      gene has been shown to contain a polymorphic poly(T) region. We have identified a
      new polymorphism G2457A in the 3'-UTR in the present study. We examined the
      relationship between these polymorphisms and mood and panic disorders, and a
      significant association between the poly(T) polymorphisms and mood disorders was
      detected (P=0.039 (allele frequency)). Associations were found between the
      polymorphisms and mood (poly(T) polymorphism: P=0.047 (allele frequency), G2457A:
      P=0.040 (allele frequency), P=0.044 (genotype frequency)) and panic disorders
      (G2457A: P=0.026 (allele frequency), P=0.011 (genotype frequency)) in males, but
      not in females. These findings suggest that the hW gene may be an important gene
      in the control of mood and anxiety as well as one of the genetic factors related
      to mood disorders and panic disorder in males. The statistical significance of
      the association remains relatively low and larger materials facilitating further
      dissection of the clinical phenotype will be needed to confirm and independently
      validate this finding and to evaluate its significance.

PMID- 10208448
TI  - Environment and vulnerability to major psychiatric illness: a case control study
      of early parental loss in major depression, bipolar disorder and schizophrenia.
AB  - The current focus on identifying genes which predispose to psychiatric illness
      sharpens the need to identify environmental factors which interact with genetic
      predisposition and thus contribute to the multifactorial causation of these
      disorders. One such factor may be early parental loss (EPL). The putative
      relationship between early environmental stressors such as parental loss and
      psychopathology in adult life has intrigued psychiatrists for most of this
      century. We report a case control study in which rates of EPL, due to parental
      death or permanent separation before the age of 17 years were evaluated in
      patients with major depression (MD), bipolar disorder (BPD) and schizophrenia
      (SCZ), compared to individually matched, healthy control subjects (MD-Control, 79
      pairs; BPD-Control, 79 pairs; SCZ-Control, 76 pairs). Loss of parent during
      childhood significantly increased the likelihood of developing MD during adult
      life (OR=3.8, P=0.001). The effect of loss due to permanent separation (P=0.008)
      was more striking than loss due to death, as was loss before the age of 9 years
      (OR=11.0, P=0.003) compared to later childhood and adolescence. The overall rate
      of EPL was also increased in BPD (OR=2.6, P=0.048) but there were no significant
      findings in any of the subcategories of loss. A significantly increased rate of
      EPL was observed in schizophrenia patients (OR=3.8, P=0.01), particularly before
      the age of 9 years (OR=4.3, P=0.01). Comparison of psychosocial, medical and
      clinical characteristics of subjects with and without a history of EPL, within
      the larger patient groups from which the matched samples were drawn (MD, n=136;
      BPD, n=107; SCZ, n=160), yielded few significant findings. Among the controls
      (n=170), however, subjects who had experienced EPL, reported lower incomes, had
      been divorced more frequently, were more likely to be living alone, were more
      likely to smoke or have smoked cigarettes and reported more physical illness
      (P=0.03-0.001). Long term neurobiological consequences of early environmental
      stressors such as maternal deprivation have been extensively studied in many
      animal species. Recently, enduring changes in hypothalamic-pituitary-adrenal axis
      function, including corticotrophin releasing factor gene expression, have
      received particular attention. Analogous processes may be implicated in the
      effect of EPL on human vulnerability to psychopathology, via alterations in
      responsiveness to stress. Genetic predisposition may influence the degree of
      susceptibility of the individual to the effects of early environmental stress and
      may also determine the psychopathological entity to which the individual is
      rendered vulnerable as a consequence of the stress.

PMID- 10208449
TI  - A comparative proteome analysis of hippocampal tissue from schizophrenic and
      Alzheimer's disease individuals.
AB  - The proteins expressed by a genome have been termed the proteome. Comparative
      proteome analysis of brain tissue offers a novel means to identify biologically
      significant gene products that underlie psychopathology. In this study we
      collected post mortem hippocampal tissue from the brains of seven schizophrenic,
      seven Alzheimer's disease (AD) and seven control individuals. Hippocampal
      proteomes were visualised by two-dimensional gel electrophoresis of homogenised
      tissue. A mean of 549 (s.d. 35) proteins were successfully matched between each
      disease group and the control group. In comparison with the control hippocampal
      proteome, eight proteins in the schizophrenic hippocampal proteome were found to
      be decreased and eight increased in concentration, whereas, in the AD hippocampal
      proteome, 35 proteins were decreased and 73 were increased in concentration
      (P<0.05). One protein, which was decreased in concentration in both diseases, was
      characterised as diazepam binding inhibitor (DBI) by N-terminal sequence
      analysis. DBI can regulate the action of the GABA(A) receptor. Protein changes
      involved 6% of the assessed AD hippocampal proteome, whereas, in schizophrenia
      protein changes involved less than 1% of the assessed hippocampal proteome. We
      conclude that schizophrenia has a subtle neuropathological presentation and
      comparative proteome analysis is a viable means by which to investigate diseases
      of the brain at the molecular level.

PMID- 10208450
TI  - Polymorphisms of the interleukin-1 gene complex in schizophrenia.
AB  - Activation of the inflammatory response system has been related to the
      pathophysiology of schizophrenia by several recent studies. Schizophrenic
      patients have varied levels of proinflammatory cytokines, such as interleukin
      (IL)-1, -6, and tumor necrosis factor (TNF)alpha in their peripheral blood or
      cerebrospinal fluid. These cytokines can modify the metabolism of
      neurotransmitters, influence neural development, and IL-1 has been implicated in
      acute, and, on the other hand, chronic neurodegeneration. They could therefore be
      of primary pathogenic importance, either in the acute disease or during those
      stages of brain development which possibly influence the sensitivity of a person
      to schizophrenia in later life. The cytokine regulation of brain development and
      its possible neuroimmune involvement in the pathogenesis of schizophrenia has
      been raised. One indication of the pathogenic role of IL-1 in schizophrenia would
      be a demonstration of the difference between schizophrenic patients and healthy
      controls at the gene level. Therefore we analyzed the polymorphism of the IL-1
      gene complex in 50 schizophrenic patients and in 400 healthy blood donors. The
      following allelisms were analyzed: IL-1beta gene: base exchange polymorphisms at
      the positions -511 (relative to the transcriptional start site); IL-1alpha gene:
      base exchange polymorphism at the position -889; IL-1 receptor antagonist (IL
      1RA) gene: variable numbers of 86-base pair tandem repeats in intron 2. The
      frequencies of the IL-1beta (-511) allele 1, IL-1alpha (-889) allele 2, and IL
      1RA allele 1 were somewhat, but not significantly, higher in the schizophrenic
      patients as compared to the controls. These alleles are known to be located on
      the same haplotype. The number of carriers of this haplotype was significantly
      higher in the schizophrenia patients (17/50 vs 81/400) than in the controls
      (P=0.026, chi2). The frequencies of this haplotype were 0.38 and 0.27,
      respectively (P=0.0266, chi2). The number of homozygotes of this haplotype was
      significantly higher in the schizophrenia patients (P=0.0006, chi2). These data
      suggest that the cytokine aberrations in schizophrenia are, at least partly,
      genetically determined.

PMID- 10208451
TI  - Endocrine and cytokine correlates of major depression and dysthymia with typical
      or atypical features.
AB  - Depression has been associated with both suppression and enhancement of various
      aspects of immune functioning. It was of interest to determine whether cytokine
      alterations associated with depression, including interleukin-1 (IL-1beta) and
      interleukin-2 (IL-2), were related to the neurovegetative symptom profile or to
      the chronicity of the illness. Circulating ACTH, cortisol, norepinephrine (NE)
      and epinephrine levels, and production of IL-1beta and IL-2 from mitogen
      stimulated lymphocytes were assessed in classical major depression, atypical
      depression (ie, with reversed neurovegetative features), and dysthymia (chronic
      depression without comorbid major depression) with either typical or atypical
      profiles, as well as nondepressed control subjects. Among atypical depressives,
      plasma ACTH levels were elevated while cortisol was reduced relative to controls.
      Irrespective of neurovegetative profile, IL-1beta production was increased in
      dysthymic patients, and was highly correlated with age-of-onset and duration of
      illness. In contrast, IL-2 production was reduced in each of the groups, although
      less so among atypical major depressives. Moreover, IL-2 production in the
      depressive groups was directly related to plasma NE levels. While neither
      depressed mood per se nor neurovegetative features accounted for this effect, it
      seemed likely that chronicity of illness or age-of-onset were associated with
      cytokine alterations. Given that circulating cytokines influence neuroendocrine
      functioning, and may affect neurovegetative features, a role for interleukins may
      exist with respect to the pathophysiology of certain subtypes of depression.

PMID- 10208452
TI  - Dopamine transporters increase in human brain after alcohol withdrawal.
AB  - Dopaminergic transmission has been suggested to be a main mechanism mediating
      reinforcement, withdrawal and craving associated with alcohol addiction. We
      measured here striatal dopamine (DA) transporter binding from 27 alcoholics
      within 4 days after cessation of prolonged heavy drinking and after a 4-week
      period of abstinence with single photon emission computed tomography (SPECT)
      using a cocaine analogue, iodine-123-beta-CIT. Controls were 29 healthy
      volunteers. Blind quantitative analyses of the SPECT data revealed markedly lower
      DA transporter binding in alcoholics on admission for detoxification than in the
      non-alcoholic controls. After a 4-week period of abstinence DA transporter
      binding increased significantly in the alcoholics (P<0.0001) reaching the levels
      of the healthy controls. The most substantial recovery in DA transporter binding
      occurred during the first 4 days of abstinence. The data indicate that prolonged
      heavy drinking decreases DA transporter binding and disturbs synaptic dopamine
      transport. This may sensitize alcoholics to dopaminergic transmission, which may
      lead to early relapse after ethanol withdrawal.

PMID- 10208453
TI  - Mapping susceptibility loci in attention deficit hyperactivity disorder:
      preferential transmission of parental alleles at DAT1, DBH and DRD5 to affected
      children.
AB  - Attention deficit hyperactivity disorder (ADHD) is a common disorder of childhood
      characterized by inattention, excessive motor activity, impulsivity, and
      distractibility. It is associated with serious disability in children,
      adolescents and adults. The etiology of the disorder is unknown, but it has a
      strong genetic component. Pharmacological and biochemical studies have suggested
      that dopaminergic and noradrenergic systems are involved. Using a sample of
      affected children and their parents we have found preferential transmission of
      alleles at polymorphisms at the dopamine transporter (DAT1), RR=1.2 (1.05-1.37),
      P=0.006, re-confirming and extending our previous findings for DAT1 (new sample
      one-tailed P=0.039); dopamine-beta-hydroxylase (DBH), RR=1.31 (1.09-1.56),
      P=0.0027; and the dopamine D5 receptor (DRD5), RR=1.67 (1.29-2.15), P=0.00005.
      Transmission of the 'associated' alleles at DAT1 and DBH is stronger in familial
      cases, RR(DAT1)=1.29 (1.04-1.59), RR(DBH)=1.49 (1.10-2.00), but for DRD5,
      transmission is stronger in non-familial cases, RR=1.59 (1.05-2.42). TDT analysis
      of complete trios supports the HHRR analysis, with P<0.05, for DAT1 P<0.005 and
      DBH and P<0.01 for DRD5. Attributable fractions for DAT1, DBH and DRD5 are
      calculated at 0.08, 0.12 and 0.20 respectively.

PMID- 10208454
TI  - Matrix metalloproteinases and carcinogenesis.

PMID- 10208455
TI  - Vasospasm, vascular injury, and atherogenesis: a perspective.
AB  - It is generally believed that injury of the vessel wall is an important condition
      for the development of atherosclerosis. The nature of this injury and its
      relationship to lesion origin, however, are not clearly understood. Based on
      early work by the author and a selective review of the literature, evidence is
      presented to show how a common cardiovascular event, vasospasm, may be one of the
      factors responsible for this tissue damage, because it produces a substantial
      arteriopathy in the very vessel in which it occurs.

PMID- 10208456
TI  - Expression of transforming growth factor beta1 and its receptors in normal human
      urothelium and human transitional cell carcinomas.
AB  - Previous studies indicated that transforming growth factor beta1 (TGFbeta1) is
      expressed by normal urothelial cells and exerts regulatory autocrine functions in
      urothelial maintenance and wound healing. However, little is known about the
      expression patterns of TGFbeta1 and its receptors in bladder tumors. Therefore,
      we studied the protein and mRNA localization of TGFbeta1 and TGFbeta receptor
      types I and II (TGFbetaRI and TGFbetaRII) in normal human urothelium and
      transitional cell carcinomas (TCCs) of different grades and stages. Expression of
      TGFbeta1 and its receptors was examined by immunocytochemistry and mRNA in situ
      hybridization in normal urothelium and TCCs using a semiquantitative method. By
      immunocytochemistry, the expression of TGFbeta1 and TGFbetaRII was higher in
      superficial and basal cell layers of normal urothelium than in the intermediate
      layer. A similar localization was seen in superficial TCCs. TGFbetaRI was mainly
      present in basal and intermediate cell layers of normal urothelium and
      superficial TCCs. In contrast, in muscle invasive TCCs, all tumor cells stained
      intensely for all three proteins. No correlation was found between immunostaining
      and TCC grade. In situ hybridization pointed out that all cell layers in normal
      urothelium exhibit similar TGFbeta1 mRNA levels. Elevated TGFbeta1 mRNA levels
      were noted in TCCs irrespective of grade or stage. In conclusion, these data
      indicate that in normal urothelium TGFbeta1, TGFbetaRI, and TGFbetaRII expression
      depend on maturation and differentiation. This pattern is particularly lost in
      muscle invasive TCCs, in which the expression of the three proteins is enhanced.
      These data suggest autocrine TGFbeta1 mechanisms in human TCC cells that may be
      more pronounced in muscle invasive TCC cells.

PMID- 10208457
TI  - Primary signet-ring cell carcinoma of the lung: histochemical and
      immunohistochemical characterization.
AB  - To establish criteria for differential diagnosis and to clarify the histogenesis
      of primary signet-ring cell carcinoma (SRCC) of the lung, five cases were studied
      by mucin-histochemical and immunohistochemical analyses and compared with SRCC of
      the gastrointestinal tract and mucus-producing adenocarcinoma of the lung. The
      proportion of signet-ring cell component varied from 10% to 90% in four cases,
      and the remaining tumor was a pure SRCC. Mucin-histochemistry showed a close
      similarity between lung SRCC and goblet cell-type or bronchial gland cell-type
      adenocarcinoma of the lung. Eighty percent of SRCCs showed positive
      immunoreactions for lactoferrin, a marker of bronchial gland cell
      differentiation, the results being consistent with the conclusions in previous
      studies that lung SRCC is closely related to bronchial gland cell-type
      adenocarcinoma. The incidence of K-ras mutation detected by the restriction
      fragment length polymorphism method was relatively high in lung SRCC (three of
      five) and goblet cell-type adenocarcinoma of the lung (four of four). Mucin
      histochemistry indicated that lung SRCC has mucin production similar to that of
      the colon and colorectal-type SRCCs of the stomach but not to that of
      gastroduodenal-type SRCC of the stomach. Immunohistochemical staining for MUC-1
      and MUC-2 glycoproteins showed a distinct difference; lung SRCC was positive for
      MUC-1 but negative for MUC-2, whereas colon SRCC and colorectal-type gastric SRCC
      were negative for MUC-1 but positive for MUC-2.Thus, by a combination of mucin
      histochemistry and MUC-1 and MUC-2 immunohistochemistry, primary lung SRCC can be
      distinguished from metastatic lung SRCC originating in the gastrointestinal
      tract.

PMID- 10208458
TI  - Elevations of DNA topoisomerase I in transitional cell carcinoma of the urinary
      bladder: correlation with DNA topoisomerase II-alpha and p53 expression.
AB  - DNA topoisomerase I (topo I) is the molecular target of the camptothecin group of
      antitumor drugs. Laboratory studies have indicated that cells sensitive to these
      drugs contain elevated levels of topo I. In this study, we immunostained 49 cases
      of transitional cell carcinoma from the urinary bladder with a monoclonal
      antibody directed against human topo I. We found elevated expression of the
      enzyme in 77% (38 of 49). This included three of six grade I tumors (50%), 9 of
      15 grade II tumors (60%), 14 of 15 grade III tumors (93%) and 12 of 13 grade IV
      tumors (92%). Because the number of cycling cells in a tumor also may be an
      important determinant of topo I drug response, a proliferation index (topo II
      alpha) also was performed for each case. The average topo II-alpha index of grade
      I tumors was 7.5 x 3.8; for grade II tumors, 20.1+/-10.5; for grade III tumors,
      40.3 x 8.2; and for grade IV tumors, 50.5+/-13.0. Because a functional p53 tumor
      suppressor gene may be necessary for anticancer drug response, we also evaluated
      our cases for alteration in p53 function. Mutations in the p53 tumor suppressor
      gene, estimated by immunohistochemical staining, were common, occurring in 23 of
      49 cases (47%). The number of cases with elevated topo I, a large growth
      fraction, and a functional p53 tumor suppressor gene was 4 of 49 (8%). Our
      results suggest that a small population of patients with transitional cell
      carcinoma of the urinary bladder may have tumors with molecular features
      suggesting responsiveness to the new anticancer drugs targeting topo I.

PMID- 10208459
TI  - h-Caldesmon in leiomyosarcoma and tumors with smooth muscle cell-like
      differentiation: its specific expression in the smooth muscle cell tumor.
AB  - h-Caldesmon (h-CD) is a protein combined with actin and tropomyosin that
      regulates cellular contraction. h-CD has been thought to be expressed exclusively
      in vascular and visceral smooth muscle cells (SMC). We examined h-CD expression
      immunohistochemically in tumors with SMC and SMC-like differentiation to clarify
      whether h-CD is specifically expressed in SMC tumors. The tumors examined in this
      study were six leiomyomas (LM), two angioleiomyomas (ALM), six leiomyosarcomas
      (LMS), eight rhabdomyosarcomas (RMS), eight malignant fibrous histiocytomas
      (MFH), four desmoids, three glomus tumors (GT), and two inflammatory
      myofibroblastic pseudotumors (IMP) of urinary bladder. We found that LM, ALM,
      LMS, and GT showed intense and extensive immunoreactivity for h-CD, whereas other
      tumors were completely negative for h-CD. In addition, h-CD was not present in
      the vascular pericytes and myofibroblasts, in contrast to actin. Although
      myoepithelial cells were immunopositive for h-CD, neoplastic myoepithelial cells
      of myoepithelial tumors and mixed tumors of the salivary gland and skin were all
      negative. These findings indicate that h-CD is a specific marker of both SMC and
      its neoplasms and that immunohistochemical detection of h-CD may facilitate the
      differential diagnosis between LMS and other tumors with SMC-like
      differentiation, including myofibroblastic tumors.

PMID- 10208460
TI  - Assessment and diagnostic utility of the cytotoxic T-lymphocyte phenotype using
      the specific markers granzyme-B and TIA-1 in esophageal mucosal biopsies.
AB  - Most esophageal intraepithelial lymphocytes (IELs) express T-cell markers.
      Increased numbers of esophageal IELs have been shown in reflux esophagitis. The
      cytotoxic potential and activity of esophageal IELs have not as yet been
      examined. Our objectives were to determine whether esophageal IELs express the
      recently described cytotoxic T-cell (CTLs) markers, TIA-1 and granzyme-B, and
      whether the number of CTLs correlates with well-defined endoscopic, clinical, and
      histological features of esophagitis. In this study, most CD-3+ esophageal IELs
      exhibit the CD-8+/TIA-1+ T cell with cytotoxic potential phenotype in both
      histologically normal biopsy specimens and in biopsy specimens with esophagitis.
      A subpopulation of esophageal IELs that express cytotoxic activity was identified
      by granzyme-B immunostaining. A significant positive association was found
      between the number of esophageal IELs seen by light microscopy in biopsy
      specimens with histological features of reflux (21 IELs/HPF) and Candida
      esophagitis (31 IELs/HPF) as compared with normal-appearing biopsy specimens (10
      IELs/HPF) (P< or =.05). Furthermore, the number of TIA-1 or granzyme-B-positive
      IELs were significantly increased in biopsy specimens with reflux esophagitis (34
      and 15 cells/HPF) and Candida esophagitis (44 and 18 cells/HPF) as compared with
      normal (11 and 2 cells/HPF) (P< or =.05). Granzyme-B and CD-3-positive IELs were
      also significantly elevated in biopsy specimens with reflux-associated squamous
      hyperplasia (P< or =.05). Finally, biopsy specimens of patients with dysphagia
      and to a lesser extent dyspepsia/heartburn exhibited increased numbers of IELs
      bearing the cytotoxic phenotype when compared with asymptomatic patients. In
      conclusion, we provide immunohistochemical evidence that most esophageal IELs
      exhibit the cytotoxic phenotype and that activated cytotoxic IELs are increased
      in reflux and Candida esophagitis.

PMID- 10208461
TI  - Bcl-6 expression in reactive follicular hyperplasia, follicular lymphoma, and
      angioimmunoblastic T-cell lymphoma with hyperplastic germinal centers:
      heterogeneity of intrafollicular T-cells and their altered distribution in the
      pathogenesis of angioimmunoblastic T-cell lymphoma.
AB  - BACKGROUND: The Bcl-6 gene product, a nuclear phosphoprotein, is expressed
      independently of Bcl-6 gene rearrangement. In lymph nodes, expression of Bcl-6
      protein is restricted to germinal center (GC) B-cells and 10% to 15% of CD3/CD4+
      intrafollicular T cells. Interfollicular cells are negative for Bcl-6 protein,
      except for rare CD3+/CD4+ T cells. Recently, we reported cases of
      angioimmunoblastic T-cell lymphoma (AITL) with hyperplastic GCs (AITL/GC), and
      observed that borders of enlarged GCs were ill defined, with features suggestive
      of an outward migration of GC cells to surrounding interfollicular zones. This
      prompted a study of follicular borders with Bcl-6 staining in reactive follicular
      hyperplasias and follicular lymphomas to compare with AITL/GC. MATERIALS AND
      METHODS: Formalin-fixed paraffin sections were used for immunostaining of Bcl-6.
      Six cases of AITL/GC, 12 nonspecific reactive follicular hyperplasia (FH), 7 HIV
      adenopathy, 10 follicular lymphoma (FL), and 8 typical AITL (ie, AITL without GC)
      were studied. Double staining for Bcl-6/CD20, Bcl-6/CD3, and Bcl-6/CD57 was
      performed in selected cases. RESULTS: In FH and HIV adenopathy, staining for Bcl
      6 revealed densely populated GCs with well-defined and regular GC borders,
      whereas Bcl-6+ cells were rare in the interfollicular areas. An occasional GC
      with an ill-defined border was invariably surrounded by a broad mantle zone;
      those with indistinct mantle zones had well-defined, regular borders. In FL,
      follicles were densely populated, and their borders were irregular, with some Bcl
      6+ cells in the interfollicular zones. In AITL/GC, GCs were less dense, GC
      borders were ill defined and irregular, and the number of interfollicular Bcl-6+
      cells was markedly increased. Double staining revealed that these interfollicular
      Bcl-6+ cells in AITL/GC were Bcl6+/CD3+/CD20-/CD57- T cells. Moreover, CD3+
      intrafollicular T cells were depleted in AITL/GC, whereas they were abundant in
      FH. Intrafollicular CD57+ cells did not stain for Bcl-6, and were also depleted
      in AITL/GC. In typical AITL, some neoplastic cells were positive for Bcl-6,
      showing variable degrees of staining. CONCLUSIONS: (1) GCs of AITL/GC differed
      from those of other reactive follicular hyperplasias and follicular lymphomas,
      and staining for Bcl-6 was useful to discern them. (2) Intrafollicular CD3+ T
      cells, many of which were also positive for Bcl-6, were markedly depleted in
      AITL/GC, with increased interfollicular Bcl-6+/CD3+ cells, suggesting an outward
      migration of intrafollicular T cells in this condition. (3) Interfollicular Bcl
      6+/CD3+ cells in AITL/GC were too numerous to be accounted for by migration
      alone, suggesting local proliferation. (4) Intrafollicular CD57+ cells were
      negative for Bcl-6, indicating heterogeneity of the intrafollicular T-cell
      population. (5) Some neoplastic cells in AITL stained for Bcl-6, suggesting up
      regulation of Bcl-6 expression in this tumor.

PMID- 10208463
TI  - Inactivation of the PTEN tumor suppressor gene is associated with increased
      angiogenesis in clinically localized prostate carcinoma.
AB  - The PTEN tumor suppressor gene encodes a dual-specificity protein phosphatase
      that may play a key role in modulating integrin-mediated signals. Inactivation of
      the PTEN gene has been detected in a small percentage of clinically localized
      prostate cancers but is common in metastatic disease. It has been shown in
      glioblastoma cell lines that loss of chromosome 10q, where the PTEN gene is
      located, is associated with increased angiogenic activity in the conditioned
      medium attributable to downregulation of thrombospondin-1, a negative regulator
      of angiogenesis. Therefore, we wished to determine whether inactivation of PTEN
      might be associated with increased angiogenesis in prostate cancers, because
      increased angiogenesis in localized cancers is associated with development of
      metastatic disease. Angiogenesis was assessed by counting microvessels in areas
      of maximal neovascularization after immunostaining with anti-factor VIII-related
      antigen antibodies in eight cases with proven homozygous deletion of the PTEN
      gene and 24 control cases. There was a statistically significant correlation
      between PTEN inactivation and increased microvessel counts. The microvessel
      density was higher at all Gleason scores in the cases with PTEN inactivation
      compared with control cases with the same score. To determine whether the
      increased angiogenesis in cases with PTEN inactivation was caused by
      downregulation of expression of the angiogenesis inhibitor thrombospondin-1, we
      analyzed a subset of the cases by immunostaining with anti-thrombospondin-1
      antibody. Approximately 25% of cases showed decreased staining of prostate cancer
      cells, but there was no correlation with PTEN inactivation. Thus, PTEN
      inactivation is associated with increased angiogenesis, but the increased
      angiogenesis is not attributable to downregulation of thrombospondin-1
      expression.

PMID- 10208462
TI  - Proliferative characteristics of intestinalized mucosa in the distal esophagus
      and gastroesophageal junction (short-segment Barrett's esophagus): a case control
      study.
AB  - Intestinalized epithelium in traditional long-segment Barrett's esophagus (BE)
      shows increased proliferative activity, which is postulated to be an early step
      in the metaplasia-dysplasia-carcinoma sequence. The aim of this study was to
      evaluate the proliferative activity of intestinalized epithelium of the distal
      esophagus and gastroesophageal junction (IMEGEJ). Tissue sections from 78
      consecutive patients (20 with IMEGEJ, 58 without IMEGEJ) who had elective upper
      gastrointestinal endoscopy over a 6-month period were immunohistochemically
      stained with MIB-1, the Ki-67 proliferation-antigen-associated marker, for
      evaluation of the crypt MIB-1 proliferation index (PI), size of the proliferative
      zone (PZ), and the presence of surface epithelial staining. Data from the IMEGEJ
      and non-IMEGEJ groups, and from 15 age-matched patients with traditional long
      segment BE (>3.0 cm), were compared statistically. IMEGEJ patients showed a
      statistically significant increase in the mean crypt PI compared with non-IMEGEJ
      controls (21.9+/-19.5 v 14.3+/-9.3; P=.01). In addition, IMEGEJ cases showed an
      increase in the mean crypt PZ (52.3+/-16.4 v 45.2+/-17.2; P=.05), and a trend
      toward an increase in the percentage of cases with MIB-1-positive surface
      epithelial cells (50% v 33%, P=.18). Patients with IMEGEJ did not differ from
      patients without IMEGEJ with respect to any other clinical or histological
      feature, including signs or symptoms of gastroesophageal reflux disease and
      presence or absence of esophagitis or carditis. The MIB-1 results of the patients
      with long-segment BE (MIB-1 PI = 22.6+/-20.5, MIB-1 PZ = 51.8+/-19.6, proportion
      of cases with MIB-1-positive surface cells = 66%) were similar to those with
      IMEGEJ. Intestinalized epithelium in the distal esophagus or gastroesophageal
      junction shows increased proliferative activity in comparison with patients
      without intestinalized epithelium. This finding supports an increased risk of
      carcinogenesis in patients with IMEGEJ.

PMID- 10208464
TI  - Immunohistochemical and clonal analysis of minute pulmonary meningothelial-like
      nodules.
AB  - The histogenesis of meningothelial-like nodule or so-called minute pulmonary
      chemodectoma remains unclear, with various immunohistochemical analyses giving
      inconsistent results. We performed an immunohistochemical and clonal analysis of
      minute pulmonary meningothelial-like nodules. Thirty-one histologically defined
      meningothelial-like nodules in 14 cases were stained immunohistochemically. One
      case had multiple lesions with brown pigment granules, which were positively
      stained with Berlin blue method, indicating the presence of hemosiderin. All
      meningothelial-like nodules were positive for vimentin and epithelial membrane
      antigen (EMA), but not for S-100 protein, chromogranin A, or synaptophysin. Five
      of 13 cases (13 of 28 lesions) were positive for CD68 by KP-1. Ten cases (24
      lesions) stained for CD68 by PG-M1 were weakly positive. All lesions were
      negative for lysozyme, myosin, actin, keratin, and melanoma-associated antigen.
      Alveolar macrophages were intensely positive for CD68 and lysozyme in all
      examined cases. We analyzed the clonality of 11 minute pulmonary meningothelial
      like nodule lesions in two female cases based on an X-chromosome-linked
      polymorphic marker, the human androgen receptor gene (HUMARA). The HUMARA was
      found to be amplified with or without prior digestion by the methylation
      sensitive restriction endonuclease HpaII. Six of 11 lesions showed monoclonal
      expansion. Five lesions in a multiple case showed different patterns of
      monoclonality. Our findings showed that minute pulmonary meningothelial-like
      nodules have meningothelial-like and phagocytic characteristics but no muscular
      phenotype. Furthermore, some minute pulmonary meningothelial-like nodules may
      show monoclonal expansion, whereas others are polyclonal. Our data indicate that
      minute pulmonary meningothelial-like nodules are reactive rather than neoplastic.

PMID- 10208465
TI  - The expanding clinical spectrum of desmoplastic small round-cell tumor: a report
      of two cases with molecular confirmation.
AB  - Desmoplastic small round cell tumor (DSRCT) is an aggressive neoplasm
      characterized by a consistent histological appearance, a unique
      immunohistochemical profile, and a specific chromosomal translocation. DSRCT is
      also hallmarked by distinctive clinical features. Most tumors arise in adolescent
      or young adult males, present as bulky abdominal masses, and diffusely spread
      along the peritoneal surface. We report two cases of DSRCT that do not fit this
      typical profile. One case involved the abdominal cavity of a 76-year-old woman.
      The other case arose in the parotid of a 22-year-old man. Histologically, the
      tumors showed the characteristic features of DSRCT. Immunohistochemically, the
      tumors showed positivity for cytokeratin, desmin, and neuron-specific enolase.
      Genetically, the tumors expressed the EWS-WT1 chimeric transcript. These two
      cases expand the differential diagnosis for poorly differentiated small-cell
      tumors that involve elderly patients or arise in the parotid. Moreover, they
      challenge the popular notion that DSRCT is a "blastomatous" tumor derived
      exclusively from the primitive mesothelium.

PMID- 10208466
TI  - Matrix metalloproteinase-1 and -3 in breast cancer: correlation with progesterone
      receptors and other clinicopathologic features.
AB  - Although matrix metalloproteinases (MMPs) are implicated in breast cancer
      progression, the contribution of MMP-1 and MMP-3 to this process, has not been
      thoroughly investigated. Matrix metalloproteinases (MMPs) are important at
      several points during multistage neoplastic progression. Immunohistochemistry
      (Strept-ABC-HRP method) and in situ hybridization were performed to detect MMP-1,
      MMM-3 proteins, and MMP-3 mRNA, respectively, in 77 infiltrative breast
      carcinomas. MMP-1, MMP-3 protein, and MMP-3 mRNA detection were analyzed in
      parallel with clinicopathologic features (menopausal status, histological type,
      nuclear and histological grade, stage) and the immunohistochemical reactivity of
      estrogen (ER), progesterone (PR) receptors, and c-erbB-2 oncoprotein in breast
      carcinomas. Statistical analysis was performed using the multiple linear
      regression test. Immunoreactivity for MMP-1 and MMP-3 was observed in 59 of 77
      (77%) and 22 of 77 (28.5%) breast carcinomas and was evaluated separately in
      cancer cells and in stromal fibroblasts. MMP-3 mRNA was detected in 72 of 77
      (93.5%) carcinomas exclusively in stromal cells within the tumors or in the
      marginal portion of tumors. MMP-1 protein immunoreactivity in stromal fibroblasts
      but not in cancer cells showed a statistically significant correlation with tumor
      stage (P=.04). MMP-1 reactivity either in stromal or in cancer cells showed a
      statistically significant inverse correlation with PR expression (P=.04 and
      P=.04, respectively). MMP-3 protein immunoreactivity in cancer or stromal cells
      and MMP-3 mRNA expression was not associated with the clinicopathologic features
      studied. MMP-3 mRNA was detected more often in ductal carcinomas. These results
      indicate that MMP-1 may contribute to breast cancer invasiveness. Furthermore,
      they suggest differential functions for MMP-1 and MMP-3 in breast cancer
      progression.

PMID- 10208467
TI  - Increased expression of membrane type 1 matrix metalloproteinase and matrix
      metalloproteinase-2 with tumor dedifferentiation in hepatocellular carcinomas.
AB  - Destruction of the extracellular matrices is required for tumor invasion and
      metastasis. Matrix metalloproteinase-2 degrades type IV collagen and laminin,
      major components of the basement membrane. Membrane type 1 matrix
      metalloproteinase activates the latent form of matrix metalloproteinase-2. We
      studied changes in membrane type 1 matrix metalloproteinase and matrix
      metalloproteinase-2 expression in relation to the tumor differentiation of
      hepatocellular carcinomas. Activity of matrix metalloproteinase-2 was also
      evaluated in hepatocellular carcinomas and noncancerous tissues. Overall, 37
      hepatocellular carcinomas were studied. Expression of membrane type 1 matrix
      metalloproteinase and matrix metalloproteinase-2 was determined by either
      immunohistochemistry (n=37) or in situ hybridization (n=6). Changes in membrane
      type 1 matrix metalloproteinase and matrix metalloproteinase-2 expression were
      evaluated in relation to tumor differentiation. Gelatinolytic activities were
      analyzed by gelatin zymography (n=4). Membrane type 1 matrix metalloproteinase
      and matrix metalloproteinase-2 were detected in hepatoma cells and stromal cells.
      In addition, these matrix metalloproteinases were detected in the same hepatoma
      cells. Increased expression of membrane type 1 matrix metalloproteinase and
      matrix metalloproteinase-2 was associated with tumor dedifferentiation. The
      active form of matrix metalloproteinase-2 was more strongly expressed by
      hepatocellular carcinomas than by noncancerous tissues. These findings indicate
      that increased expression of membrane type 1 matrix metalloproteinase and matrix
      metalloproteinase-2 was associated with tumor dedifferentiation, suggesting that
      these matrix metalloproteinases are intimately involved in the invasion of
      hepatocellular carcinomas.

PMID- 10208468
TI  - Collagenous colitis: a study of the distribution of morphological abnormalities
      and their histological detection.
AB  - In collagenous colitis, the literature is conflicting concerning where in the
      colon the lesions are most likely to be present and most severe. Conflicting data
      furthermore shed doubt on the sensitivity of the histological detection of the
      morphological abnormalities and the threshold criteria for diagnosis. We
      addressed these questions in 56 patients with collagenous colitis. Two hundred
      ninety-one coded biopsy specimens were analyzed according to six standardized
      sites from cecum to rectum. Subepithelial collagen deposits were subjectively
      graded in hematoxylin and eosin (H&E) sections and quantitatively measured in
      trichrome-stained sections, respectively. Semiquantitative grading was also done
      for inflammatory changes of the lamina propria and abnormalities of the surface
      and crypt epithelium. The transverse colon yielded the largest percentage of
      biopsy specimens (83%) interpreted as diagnostic of collagenous colitis and also
      had the largest percentage of biopsy specimens with inflammatory changes (98%).
      Biopsy specimens from both the rectosigmoid and the right colon (ascending and
      cecum) were significantly less likely to be diagnostic (P<.01). Only 66% of
      specimens obtained from the rectosigmoid were diagnostic, and 18% of these were
      interpreted as normal. Subepithelial collagen deposits proved to be significantly
      thicker in the transverse (median, 46.8 microm; range, 12 to 212.4) and
      descending (median, 49.2 microm; range, 6 to 230.4) than in the rectosigmoid
      (median, 33.6 microm; range, 9.6 to 178.8) and right colon (median, 35.4 microm;
      range, 6 to 140.4), respectively (P<.01). Almost all biopsy specimens (97%) had
      collagen deposits thicker than 10 microm. However, the subjective interpretation
      "diagnostic of collagenous colitis" proved to be most consistent with a threshold
      of 30 microm. Our results indicate that biopsy specimens from at least as
      proximal as the transverse colon should be obtained to definitely rule out
      collagenous colitis. Furthermore, it is evident that in a given biopsy specimen,
      markedly abnormal subepithelial collagen deposition had to be present for an
      unequivocal histological diagnosis of collagenous colitis.

PMID- 10208469
TI  - Downregulation and abnormal expression of E-cadherin and beta-catenin in
      nasopharyngeal carcinoma: close association with advanced disease stage and lymph
      node metastasis.
AB  - Nasopharyngeal carcinoma (NPC) is predominantly of the undifferentiated
      histological subtype. Histological differentiation is of limited prognostic
      significance in NPC. Recent studies have suggested that downregulation of the
      cadherin-catenin cell adhesion complex may play a crucial role in the initial
      stage of cancer invasion and metastasis and is associated with poor prognosis in
      human cancers. Expression of E-cadherin has not been reported previously in NPC,
      and its prognostic value in NPC is unknown. The purpose of this study was to
      examine the expression pattern of E-cadherin and its associated partner, beta
      catenin, in NPC and their possible applications as prognostic markers to predict
      the clinical outcome of NPC. Expression of the E-cadherin and beta-catenin was
      examined by immunohistochemical methods in 74 cases of primary NPC and 17 of
      their corresponding lymph node metastases. Normal nasopharyngeal epithelium
      showed strong and homogeneous immunocytochemical staining of E-cadherin and beta
      catenin at the cell membranes and intercellular junctions. In contrast, primary
      NPC showed variable and heterogeneous staining patterns of E-cadherin and beta
      catenin. Loss of membranous E-cadherin expression was significantly associated
      with advanced stages of diseases (P<.001). Eighty percent to ninety percent of
      NPC in stages IV and V (Ho's staging), respectively, showed a reduced (<35%)
      membranous staining of E-cadherin compared with normal nasopharyngeal epithelium.
      Expression of beta-catenin also was downregulated in advanced NPC. Ninety percent
      to one hundred percent of NPC in stages IV and V (Ho's staging) expressed a
      reduction (<35%) of imnmunocytochemical staining of beta-catenin. The expression
      pattern of beta-catenin staining was strongly associated with the expression of E
      cadherin (P<.001). Unlike E-cadherin, nuclear staining of beta-catenin expression
      was observed in some of the primary NPC and lymph node metastasis. Reduced
      expression of E-cadherin and beta-catenin expression was associated with a
      shorter survival of NPC patients (P<.001). In advanced NPC patients (stages IV
      and V), a significant difference in survival was observed in tumors with higher
      or lower levels of E-cadherin expression (P=.0224, log-rank test). These
      observations suggests that expression of E-cadherin and beta-catenin may have
      prognostic values in NPC patients.

PMID- 10208470
TI  - Monoclonal antibody Adnab-9 defines a preneoplastic marker in epithelium at risk
      for adenocarcinoma of the small intestine.
AB  - Unlike colorectal cancer, risk markers for adenocarcinoma of the small intestine
      (ASI) have not been identified. Because the demographic and pathological features
      of both of these diseases are similar, immunohistochemistry was performed using
      monoclonal antibodies for three colonic premalignant markers, Adnab-9 (recognizes
      a colonic adenoma epitope), CaCo3/61, and FBB2/29 (small intestine proteoglycans
      expressed ectopically in colonic neoplasms), in normal and neoplastic small
      intestinal epithelium, and the results were compared with normal controls. Adnab
      9 was also examined in 20 familial adenomatous polyposis (FAP) patients, a
      population known to be at an increased risk for ASI. Immunohistochemistry in
      normal and neoplastic tissue (adenoma, adenocarcinoma) from 18 patients with
      primary adenocarcinoma of the small intestine was compared with normal small
      intestine from 10 nonneoplastic controls. Four of 10 (40%) cases of normal small
      intestinal epithelium from controls were mildly positive in less than 10% of
      crypts, versus strong staining (>50% of crypts) in 16 of 18 (89%) patients with
      adenocarcinoma, and in 17 of 20 (85%) patients with FAP (P<.05). Adnab-9
      predominantly stained Paneth cells as well as rare crypt and basal villous goblet
      cells. Adenomatous epithelium from the adenocarcinoma cases and adenomas from the
      FAP patients showed staining of Adnab-9 in 63% and 78% of cases, respectively.
      Only 17% of adenocarcinomas were positive for Adnab-9. In contrast, neither
      CaCo3/61 nor FBB2/29 showed any significant differences in the degree of staining
      in normal small intestinal epithelium in patients with adenocarcinoma compared
      with controls. Enhanced Adnab-9 staining in normal small intestinal epithelium
      from patients who harbor adenocarcinoma, and in FAP patients, supports its role
      as a risk marker of small intestinal neoplasia.

PMID- 10208471
TI  - Immunohistochemical study on transforming growth factor-beta1 expression in liver
      fibrosis of Down's syndrome with transient abnormal myelopoiesis.
AB  - A case of Down's syndrome associated with liver fibrosis is reported. The
      fibrosis was diffusely distributed along sinusoids, and an excess of
      megakaryocytes was also found in the liver. To determine the mechanism of liver
      fibrosis in Down's syndrome, we immunohistochemically stained the liver with
      markers of myofibroblast-like cells, antialpha smooth muscle actin antibodies and
      antidesmin antibodies. The myofibroblast-like cells were found along sinusoids,
      suggesting that liver fibrosis in Down's syndrome is caused by the myofibroblast
      like cells derived from Ito cells/lipocytes. The expression of transforming
      growth factor (TGF)-betal, which is an important mediator of the activation of
      lipocytes, was immunohistochemically examined. The accumulation of TGF-betal was
      observed in cells in the sinusoidal spaces, which involve the intracellular
      expression of megakaryocytes. Together, these findings suggest that megakaryocyte
      derived TGF-betal is one of the likely candidates in the lipocyte activation of
      liver fibrogenesis in Down's syndrome.

PMID- 10208472
TI  - Virtual microscopy: high resolution digital photomicrography as a tool for light
      microscopy simulation.
AB  - Recent advances in microcomputers and high resolution digital video cameras
      provide pathologists the opportunity to combine precision optics with digital
      imaging technology and develop new educational and research tools. We review
      recent advances in virtual microscopy and describe techniques for viewing digital
      images using a microcomputer-based workstation to simulate light microscopic
      examination, including scanning at low power to select features of interest and
      zooming to increase magnification. Hardware and software components necessary to
      acquire digital images of histological and cytological slides, and closely
      simulate their examination under a light microscope are discussed. The
      workstation is composed of a MicroLumina digital scanning camera (Leaf Systems,
      Southborough, MA), light microscope (Olympus Optical Co., Lake Success, NY),
      Pentium (Intel Corp., Santa Clara, CA) 166 MHz microcomputer configured with 64
      megabytes of random access memory (RAM), a MGA Millenium Powerdesk graphics card
      (Matrox Graphics, Inc., Montreal, Canada) and Photoshop software (Adobe Systems
      Inc., San Jose, CA) running in a Windows 95 (Microsoft Corp., Redmond, WA)
      environment. Images with spatial resolutions of up to 2700 x 3400 pixels in 36
      bit color, can be displayed simultaneously as distinct images in a montage, or
      merged into a single composite image file to highlight significant features of a
      histological or cytological slide. These image files are saved in Joint
      Photographers Experts Group (JPEG) format using compression ratios of up to 80:1
      without detectable visual degradation. The advantages and technical limitations
      of various workstation components are addressed and applications of this
      technology for pathology education, proficiency testing, telepathology, and
      database development are discussed.

PMID- 10208473
TI  - An unusual cervical carcinoma showing exception to epitheliotropism of human
      papillomavirus.
AB  - Human papillomaviruses (HPV) infect epithelial tissues but have not been
      previously detected within mesenchymal cells. During a systematic investigation
      of FIGO stage Ib cervical cancers with colorimetric in situ hybridization, we
      detected HPV 16 DNA within the stromal compartment of an unusual undifferentiated
      carcinoma. The mesenchymal nature of the HPV-containing cells was confirmed by
      immunohistochemistry and electron microscopy. No viral particles were identified.
      Sequencing the majority of the HPV 16 genome identified few changes from the
      revised reference clone; all previously reported in other HPV 16 variants. These
      viral changes are unlikely to explain the exceptional mesenchymal localization of
      the HPV 16 DNA in this case.

PMID- 10208474
TI  - Bcl-2 staining in pheochromocytomas.

PMID- 10208475
TI  - Chronic infection in the aetiology of atherosclerosis--focus on Chlamydia
      pneumoniae.
AB  - An inflammatory basis to atherosclerosis is now accepted. It remains plausible
      (but unproven) that common infectious agents may contribute to the inflammatory
      signal, and hence the development (and/or progression of atherosclerosis and its
      clinical sequelae. Of the candidate microorganisms implicated, Chlamydia
      pneumoniae has emerged as the most likely pathogen to have a casual role.
      Evidence for this is based on sero-epidemiological, pathological and laboratory
      based evidence, in addition to early animal models and small-scale antibiotic
      studies. A past decade of research has now culminated in prospective antibiotic
      intervention trials in coronary heart disease to be conducted. The results of
      these studies should help to finally determine whether infection with C.
      pneumoniae is a pathogenetic factor in atherosclerosis, and whether antibiotic
      therapy has a role in the secondary prevention of coronary heart disease.

PMID- 10208476
TI  - Local changes in collagen content in rabbit aortic atherosclerotic lesions with
      time.
AB  - A video-microdensitometry method was used to quantify collagen on a pixel by
      pixel basis at specific locations within atherosclerotic lesions, induced by
      feeding New Zealand White rabbits a declining cholesterol diet. Probability
      mapping (done previously) showed the lesions occurred in predictable locations so
      the age of any one area of a lesion could be estimated. The oldest part of the
      lesion was on the lateral lip of the flow divider as lesions always developed
      there first. Serial sections through three lesions showed the distribution of
      collagen within the plaque. The measurement of all the lesions showed that early
      lesions had low collagen levels: 3-6% for the intercostals and 8-11% for the
      renals. Collagen increased consistently with time on the diet to 11-15%, for the
      intercostal and approximately 17% for the renal. The aorto-renal lesions were
      more severe; thicker and with a higher percentage of collagen. The greatest
      collagen content was on the lateral lip of the flow dividers, where controls had
      intimal thickening. No fibrous caps were seen. This study shows conclusively that
      collagen is not evenly distributed in lesions, but develops progressively in
      specific locations of fatty plaques with the duration of cholesterol feeding.
      Intimal thickening predisposes to early collagen development.

PMID- 10208477
TI  - Progression and regression of atherosclerosis in APOE3-Leiden transgenic mice: an
      immunohistochemical study.
AB  - Apolipoprotein E3-Leiden (APOE3-Leiden) transgenic mice develop hyperlipidemia
      and are highly susceptible to diet-induced atherosclerosis. We have studied the
      progression and regression of atherosclerosis using immunohistochemistry. Female
      transgenic mice were fed a moderate fat diet to study atherosclerosis over a
      longer time period. Fatty streaks arose in the intima and consisted of lipid
      filled macrophages which differed in origin. All macrophages expressed the
      macrophage scavenger receptor while two thirds expressed sialoadhesin and were
      positive for an antibody recognizing marginal zone macrophages (MOMA-1). All
      macrophages were negative for the scavenger receptor MARCO and 50% were positive
      for CD4. Small fatty streaks contained CD-3 positive T-lymphocytes which were for
      more than 70% CD4-positive. ICAM-1 was positive both in atherosclerotic and
      control mice. In early plaques, fibrosis was observed on the luminal and medial
      site of the foam cells while smooth muscle cells were only observed in the
      fibrous cap. To study regression, we used a high fat, high cholesterol diet to
      rapidly induce atherosclerosis (14 weeks). The animals were then fed normal chow.
      Subsequently, atherosclerosis was assayed over time (4, 8, 16 weeks). Cholesterol
      levels dropped in 4 weeks to control levels. The animals did not show a
      significantly decrease in plaque size over time. but the percentage macrophages
      was significantly smaller in the animals after 4 weeks. In conclusion, the APOE3
      Leiden mouse is a useful model to study the progression and regression of
      atherosclerosis.

PMID- 10208478
TI  - Relation between non-uniform hemodynamics and sites of altered permeability and
      lesion growth at the rabbit aorto-celiac junction.
AB  - Using the rabbit's aorto-celiac junction as a representative atherosclerotic
      model, the hemodynamics of a bifurcating blood vessel are numerically simulated
      and three hemodynamic parameters are compared. The wall shear stress (WSS), the
      oscillatory shear index (OSI), and the spatial wall shear stress gradient (WSSG)
      are considered in this study. Locally enhanced wall permeabilities and intimal
      macrophages are generally considered to be involved in atherogenesis, and here
      the primary concern is with the hemodynamic influence on these early stages of
      the disease process. In comparing the segmental averages of the indicator
      functions and previously published intimal white blood cell densities, only the
      WSSG shows a statistically significant correlation. All three indicators have
      selective strengths in determining sites of early lesion growth around the aorto
      celiac flow divider. At the proximal end of the flow divider on the lateral side
      of the orifice, there are elevated values of the OSI as well as WSSG and low WSS
      values. Regions of elevated wall permeabilities compare with the regions of
      elevated WSSG along the lateral and distal portions of the flow divider. Largely
      dependent upon the present input pulse with reverse flow, the OSI indicates
      relatively high values throughout the flow domain, however, it is important when
      utilized in conjunction with low WSS regions. This study presents a rationale for
      further quantitative correlative studies in the rabbit model based on additional
      histological data sets.

PMID- 10208479
TI  - The type of mutation in the low density lipoprotein receptor gene influences the
      cholesterol-lowering response of the HMG-CoA reductase inhibitor simvastatin in
      patients with heterozygous familial hypercholesterolaemia.
AB  - In a genetically heterogeneous group of 109 patients with a clinical diagnosis of
      heterozygous familial hypercholesterolaemia (FH), the influence of gender,
      apolipoprotein (apo) E genotype and the type of molecular defect in the LDL
      receptor (LDLR) gene on the reduction of plasma LDL-cholesterol levels to
      treatment with a HMG-CoA reductase inhibitor (simvastatin) were studied. Response
      was determined as the percentage fall in LDL-cholesterol from untreated levels
      and as the proportion of patients where levels fell below 4.9 or 4.1 mmol/l. Of
      the patients, 86 individuals had tendon xanthomata (TX+) and a diagnosis of
      'definite' FH and these individuals presented with a significantly higher
      untreated LDL-cholesterol compared to the 23 individuals who did not have
      xanthomas (TX-) and a diagnosis of 'probable' FH (8.14+/-0.19 vs. 6.81+/-0.25, P=
      0.001). Overall, HMG-CoA reductase inhibitor doses of 10, 20 or 40 mg/day
      resulted in a significant fall of LDL-cholesterol levels of 29, 39 and 49%, but
      at all doses those with TX had significantly higher levels than those without,
      and significantly fewer TX + patients achieved LDL-cholesterol levels below 4.9
      or 4.1 mmol/l than the TX - group (P < 0.05 at each dose). In the TX+ group the
      response to treatment was of similar magnitude in men and women and in patients
      with different apoE genotype. In the 'probable' FH probands only three mutations
      were identified (detection rate 13%), one in the LDLR gene and two in the APOB
      gene, a detection rate significantly lower (P= 0.02) than in the 'definite' FH
      probands where 28 mutations were detected (detection rate 37%). In the TX +
      patients where no mutation was detected, treatment resulted in a greater
      proportion achieving LDL-cholesterol levels below 4.9 and 4.1 mmol/l compared to
      those with any LDLR mutation, this difference was close to statistical
      significance at the 4.9 mmol/l threshold at 10 mg/day (41 vs. 13%, P = 0.058).
      For the 14 patients with an LDLR mutation that was predicted to be 'severe',
      fewer achieved LDL-cholesterol levels below 4.9 or 4.1 mmol/l at each dosage
      compared to the 16 individuals with 'mild' mutations, and this difference was
      statistically significant at the maximal dosage of 40 mg/day (P = 0.018). Thus
      although characterisation of the molecular defect in FH patients may not be
      relevant to their immediate clinical management, those with a particular mutation
      may need more aggressive lipid-lowering treatment to reach LDL-cholesterol levels
      recommended to reduce the risk of coronary heart disease (CHD).

PMID- 10208480
TI  - Analysis of serum lipid levels in Japanese men and women according to body mass
      index. Increase in risk of atherosclerosis in postmenopausal women. Research
      Group on Serum Lipid Survey 1990 in Japan.
AB  - Relatively low serum lipid levels are thought to be an important factor
      contributing to the low incidence of ischemic heart diseases (IHD) in Japanese.
      It has been proven that obesity or overweight constitutes a basal condition for
      several risk factors in atherosclerosis. The purpose of this study is to obtain
      data on serum lipids and lipoprotein profiles in relation to body mass index
      (BMI), which will enable us to compare the nature and weight of metabolic risk
      factors in atherosclerosis between Japanese and people in Western countries. Data
      of total serum cholesterol, triglyceride, and HDL-cholesterol levels of Japanese
      men and women obtained from a large-scale survey in 1990 were analysed according
      to BMI for different age groups. Apolipoprotein A-I and B and Lp(a) were also
      measured in randomly selected samples and their contribution as a risk factor was
      estimated especially in postmenopausal women. The subjects in two age groups of
      men (20-39 and 40 59 years) and women (20 39 and 50-69 years) were graded into
      quintiles according to the BMI. The middle grades of BMI were 21.9-23.3 and 22.4
      23.6 for younger and older men, and 20.0-21.1 and 22.2-23.6 for younger and older
      women, respectively. These values are much lower than those in Western
      populations, the border between the IVth and the top quintile almost
      corresponding to the average for Americans. Total cholesterol showed a tendency
      to shift into higher ranges in all age groups in both men and women as BMI
      increased, with the highest distribution remaining in the range of 160-199 mg/dl
      (4.2-5.2 mmol/l). The average cholesterol levels for the top quintile of BMI were
      still lower than most of the average values in Western populations. The
      distribution of cholesterol in higher ranges was much greater and the difference
      according to BMI was smaller in older women than in men. In both men and women,
      whether younger or older, about 90% of the subjects in the lower quintiles of BMI
      had triglyceride levels lower than 150 mg/dl. The distribution in the higher
      range of triglyceride was small in women, not only at younger ages but also in
      postmenopausal women at the top quintile of BMI. About 85% of the younger women
      with a middle grade of BMI had an HDL-cholesterol level higher than 50 mg/dl. The
      values in postmenopausal women were still higher than in men aged 40-59 years.
      Shift of the distribution curves of HDL-cholesterol according to BMI was similar
      in all groups and more remarkable than the change in triglyceride. The average
      HDL-cholesterol levels at the top quintile were almost comparable to the average
      values in Western countries; the difference in HDL-cholesterol levels between the
      two populations can mostly be explained by the difference in BMI. Smokers showed
      a slightly lower total cholesterol and significantly (3-4 mg/dl) lower HDL
      cholesterol levels, although there was no difference in distribution of BMI
      between smokers and non-smokers. Relatively low total cholesterol levels even in
      smokers has probably contributed to the low incidence of IHD in spite of the high
      frequency of smoking in Japanese population. Mean Lp(a) levels showed a tendency
      to increase after age 40 in women. BMI itself did not have a correlation with
      serum Lp(a) levels. The distribution curve of Lp(a) shifted to higher levels as
      total cholesterol increased and the tendency was most remarkable in women around
      or after the menopause. It was remarkable in older women that as the total
      cholesterol or apo B level increased there was also an increased prevalence of
      abnormal ECG with a pattern of myocardial ischemia. Postmenopausal women seem to
      have a great risk of atherosclerosis regarding the lipid and lipoprotein profile
      even in the Japanese population.

PMID- 10208481
TI  - Lipopolysaccharide enhances oxidative modification of low density lipoprotein by
      copper ions, endothelial and smooth muscle cells.
AB  - The effect of lipopolysaccharide (LPS, endotoxin) on low density lipoprotein
      (LDL) oxidative modification by copper ions, endothelial and smooth muscle cells
      was studied by determination of the level of lipid peroxidation products
      (thiobarbituric acid reactive substances or TBARS), the diene level and the
      electrophoretic mobility of the LDL particle. LPS 25-75 microg/ml induced a dose
      dependent increase in LDL oxidation by copper ions, endothelial and smooth muscle
      cells. At 75 microg LPS/ml, the TBARS content was 1.9, 1.6, and 1.8-fold
      increased, respectively. The LDL degradation by J774 macrophage-like cells was
      concomitantly stimulated. Preincubation of the LDL particle with LPS induced a
      marked increase in the subsequent LDL oxidative modification either by copper
      ions or by endothelial and smooth muscle cells. In addition, pretreatment of
      endothelial and smooth muscle cells with LPS also induced an enhancement of LDL
      oxidative modification performed in the absence of LPS. This effect was
      accompanied by a parallel increase in superoxide anion release by the cells.
      These results point at one of the mechanisms involved in the described
      association between bacterial infection and acute myocardial infarction as well
      as coronary heart disease.

PMID- 10208482
TI  - Expression of plasminogen activator inhibitor-1 in human adipose tissue: a role
      for TNF-alpha?
AB  - Elevated plasminogen activator inhibitor-1 (PAI-1) plasma levels, responsible for
      reduced fibrinolysis, are associated with animal and human obesity and with
      increased cardiovascular disease. The expression of PAI-1 has been found recently
      in animal and human adipose tissue. Factors and mechanisms regulating such an
      expression remain to be elucidated. In omental and/or subcutaneous biopsies from
      obese non-diabetic patients, incubated in Medium 199, we have confirmed that
      human adipose tissue expresses PAI-1 protein and mRNA; furthermore we have
      demonstrated that such an expression is clearly evident also in collagenase
      isolated human adipocytes and that it is stimulated by incubation itself and
      enhanced by exogenous human tumor necrosis factor-alpha (h-TNF-alpha). Since
      human adipose tissue produces TNF-alpha, to further characterize the relationship
      of PAI-1 to TNF-alpha, human fat biopsies were also incubated with Pentoxifylline
      (PTX) or Genistein, both known to inhibit endogenous TNF-alpha through different
      mechanisms. PTX caused a dose-dependent decrease of basal PAI-1 protein release,
      reaching 80% maximal inhibitory effect at 10(-3)M, the same inhibitory effect
      caused by Genistein at 100 microg/ml. This was associated to a marked inhibition
      of PAI-1 mRNA and of endogenous TNF-alpha production. Furthermore, when human fat
      biopsies were incubated in the presence of polyclonal rabbit neutralizing anti
      human TNF-alpha antibody (at a concentration able to inhibit 100 UI/ml human TNF
      alpha activity), a modest but significant decrease of the incubation induced
      expression of PAI-1 mRNA was observed (19.8+/-19.0% decrease, P = 0.04, n = 7).
      In conclusion, the results of this study demonstrate that PAI-I expression is
      present in human isolated adipocytes and that it is enhanced in human adipose
      tissue in vitro by exogenous TNF-alpha. Furthermore our data support the
      possibility of a main role of endogenous TNF-alpha on human adipose tissue PAI-1
      expression. This cytokine, produced by human adipose tissue and causing insulin
      resistance, may be a link in the clinical relationship between insulin-resistance
      syndrome and increased PAI-1 plasma levels.

PMID- 10208483
TI  - Influence of hypercholesterolemia and endothelin-3 pre-treatment on the effects
      of shear forces on platelet aggregation and cyclic GMP content.
AB  - Shear forces induce platelet aggregation and stimulate the endothelial production
      of anti-aggregatory factors. Among them, endothelin-3 (ET-3) has been reported to
      reduce aggregation and to increase platelet cyclic GMP (cGMP) content. Since
      hypercholesterolemia modifies both platelet aggregability and endothelial
      function, we compared in 14 hypercholesterolemic and 15 normocholesterolemic
      subjects the influences of shear forces (240 and 650 s(-1)) on platelet
      aggregation and cGMP content, and their modulation by ET-3. Spontaneous maximal
      aggregation occurred earlier and at a greater extent in hypercholesterolemic than
      in normocholesterolemic subjects (63+/-2 vs 46+/-6% P < 0.01). Pre-treatment with
      ET-3 abolished the shear-induced facilitation of maximal aggregation in platelets
      of normocholesterolemic (from 70+/-2 to 52+2% at 240 s(-1) and from 73+/-1 to
      59+/-2S at 650s(-1); P < 0.05) and hypercholesterolemic (from 78+/-3 to 64+/-2 at
      240 s(-1) and from 78+/-2 to 66+/-3 at 650 s(-1); P < 0.05) subjects. cGMP
      content did not significantly differ between normocholesterolemic and
      hypercholesterolemic subjects (6.1+/-0.5 vs 6.9+/-0.7 pmol/10(9) platelets). It
      was reduced in platelets submitted to shear forces (P < 0.05). This shear
      dependent reduction was suppressed by ET-3 pre-treatment. These results
      demonstrate that shear forces enhance platelet aggregation and diminish their
      cGMP content. ET-3 reduces the pro-aggregating effects of shear, suggesting a
      rise in cGMP content as a dynamic associated mechanism.

PMID- 10208484
TI  - P1A1/A2 polymorphism of platelet glycoprotein IIIa and risk of acute coronary
      syndromes in heterozygous familial hypercholesterolemia.
AB  - Familial hypercholesterolemia (FH) is an autosomal inherited disorder caused by
      different mutations in the low density lipoprotein (LDL) receptor gene. It has
      been demonstrated that there is an increased risk of coronary heart disease (CHD)
      in heterozygous FH subjects, although this excess CHD is not only explained by
      the LDL-cholesterol concentration or the class of the LDL-receptor mutation. To
      investigate if a common polymorphism at the platelet glycoprotein (GP) IIIa gene
      locus could be related to CHD phenotypic variation in heterozygous FH. we have
      carried out a case-control study. We have studied 40 cases and 40 controls
      matched for age, sex and genetic defect in the LDL-receptor gene. Allele
      frequency of PI(A2) polymorphism for cases and controls was 20 and 22.5%,
      respectively, and the difference was not significant. In conclusion, our data do
      not support any association between the GP IIIa polymorphism and the increased
      prevalence of acute coronary syndromes in the heterozygous FH subjects.

PMID- 10208486
TI  - Monocyte chemotactic protein-1 gene and protein expression in atherogenesis of
      hypercholesterolemic rabbits.
AB  - Monocyte adherence to the endothelium and subsequent migration into the
      subendothelial space are important early events in atherogenesis. Monocyte
      chemotactic protein-1 (MCP-1) has been shown to be highly expressed in both human
      atheroma and advanced atherosclerotic lesions of experimental animals. To
      establish the temporal correlation between MCP-1 expression and plaque
      development, we examined the expression of MCP-1 during atherogenesis of
      hypercholesterolemic rabbits using Northern blot analysis, in situ hybridization,
      and immunohistochemistry. New Zealand White rabbits were fed with 2% cholesterol
      containing diet for 1 day, 3 days, 1 week, 3 weeks or 6 weeks. The plasma levels
      of total cholesterol were significantly increased 3 days after cholesterol
      feeding and continued to increase during the entire cholesterol-feeding period.
      Northern blot analysis showed that MCP-1 mRNA levels remained unchanged following
      cholesterol feeding for up to 1 week, were higher than control levels at 3-week
      and increased even higher at 6-week. In situ hybridization showed that after 3
      weeks of cholesterol feeding, MCP-1 mRNA expression was up-regulated in newly
      formed fatty streaks and parts of tunica media in the presence or absence of
      fatty streaks. At 6-week, pronounced MCP-1 mRNA expression was detected with
      similar distribution. In contrast, MCP-1 mRNA was detected only in a few
      endothelial cells and adventitia in control and experimental groups feeding
      cholesterol up to 1-week. Immunostaining of serial sections indicated that MCP-1
      was expressed by macrophages and smooth muscle cells in rabbits fed with
      cholesterol for 3 or 6 weeks. No MCP-1 was detected in intima or media in all
      other groups. These results show that a lag period exists between serum
      cholesterol increase and upregulation of MCP-1 expression, suggesting that
      cholesterol modifications (e.g. oxidation) are required to stimulate MCP-1
      expression. In addition, MCP-1 expressed by both macrophages and smooth muscle
      cells during the initial stages of atherosclerosis is likely to contribute to the
      development of fatty streaks in hypercholesterolemic rabbits.

PMID- 10208485
TI  - Immunization with bacillus Calmette-Guerin vaccine increases aortic
      atherosclerosis in the cholesterol-fed rabbit.
AB  - New Zealand White rabbits were injected subcutaneously with either a human dose
      of bacillus Calmette Guerin (BCG) vaccine (n = 7) or saline (n = 7). A further
      half dose of BCG or saline was injected after a further 4 weeks. The animals were
      subsequently fed a 0.25-1% cholesterol diet for 10 weeks, 8 weeks after the first
      injection. The rabbits were killed and perfusion fixed with 4% paraformaldehyde.
      The integrated plasma cholesterol levels did not differ significantly between the
      groups (P > 0.05). Plasma levels of anti-mycobacterial antibodies rose following
      BCG immunization, reaching a peak after 8 weeks (P < 0.05) compared to basal
      titers and the control group. BCG immunization was also associated with increased
      peripheral lymphocyte and monocyte activation, as evidenced by increased surface
      expression of IL-2 receptor (CD25) (P < 0.02) and MAC-I (CD11b) (P < 0.05),
      respectively. Significantly more mononuclear cells bound to the aortic
      endothelium of BCG immunized, cholesterol-fed rabbits (1.93+/-0.77 mononuclear
      cells/1000 endothelial cells) than to that of saline immunized rabbits (0.08+/
      0.08 mononuclear cells/1000 endothelial cells; P < 0.01). The aortic
      intimal:medial ratio was greater in the BCG immunized rabbits (0.19+/-0.08) than
      those treated with saline (0.04+/-0.03; P < 0.05). This suggests that BCG
      immunization enhances peripheral leucocyte activation, aortic monocyte
      recruitment and atherogenesis in the cholesterol-fed rabbit.

PMID- 10208487
TI  - HDL composition and HDL antioxidant capacity in patients on regular
      haemodialysis.
AB  - Recent evidence suggests that HDL can directly inhibit LDL oxidation, a key early
      stage in atherogenesis. Patients with chronic renal failure are at increased
      cardiovascular risk, have reduced HDL levels and altered HDL composition. We have
      therefore investigated whether compositional changes in HDL lead to decreased HDL
      antioxidant capacity in these patients. In comparison to control subject HDL,
      patient HDL contained less total cholesterol, cholesterol esters, phospholipids
      and alpha-tocopherol. LDL, HDL and LDL + HDL were standardised for protein and
      oxidised in the presence of Cu2+. The rate of propagation during HDL oxidation
      was reduced in the patient group (3.28+/-0.65 x 10(-5) vs. 4.60+/-0.97 x 10(-5)
      abs. U/min, P < 0.01). Lipid peroxide generation in patient HDL was decreased:
      6.56+4.4 versus 13.42+/-7.0 nmol malondialdehyde (MDA)/mg HDL protein after 90
      min and 14.45+/-3.8 versus 20.11+/-7.8 nmol MDA/mg HDL protein after 180 min.
      This is attributable to reduced HDL polyunsaturated fatty acid content in
      patients (0.53+/-0.12 vs. 0.72+/-0.16 mmol/g HDL, P < 0.01). The inhibitory
      effect of HDL on LDL oxidation was similar: 71 and 33% for patient HDL compared
      to 68 and 31% for control HDL, after 90 and 180 min, respectively. Compositional
      changes of HDL in patients on haemodialysis did not affect the antioxidant
      capacity of HDL after standardisation for HDL protein. However, reduced HDL
      levels in vivo may result in reduced HDL antioxidant capacity in these patients.

PMID- 10208488
TI  - Effect of hypoxia and hypoxia/reoxygenation on proteoglycan metabolism by
      vascular smooth muscle cells.
AB  - Hypoxia and hypoxia/reoxygenation are known to affect vascular smooth muscle cell
      physiology. In this study, we first investigated proteoglycan synthesis by human
      aortic smooth muscle cells exposed to normoxia, hypoxia, or
      hypoxia/reoxygenation. We then compared the newly synthesized proteoglycans from
      normoxic and hypoxic-reoxygenation cultures for their ability to bind low density
      lipoprotein (LDL). Confluent smooth muscle cells under normoxia, hypoxia, or
      hypoxia/reoxygenation were pulsed with [35S]sulfate, and secreted and cell
      associated proteoglycans were analyzed. Secreted proteoglycans in cultures
      exposed to hypoxia (4 h)/reoxygenation (19 h) increased 28% over those of cells
      continuously exposed to normoxia. Cell-associated proteoglycans did not differ
      significantly between the two groups. In contrast, hypoxia (4 h) followed by a 30
      min reoxygenation produced a 37% decrease in newly synthesized proteoglycans.
      Hypoxia alone also resulted in a 24% decrease in secreted proteoglycans and a 20%
      decrease in cell-associated proteoglycans. Proteoglycans newly synthesized by
      smooth muscle cells exposed to normoxia and hypoxia/reoxygenation did not differ
      in their charge densities and molecular size but did differ in glycosaminoglycan
      composition. Exposure of smooth muscle cells to hypoxia/reoxygenation produced a
      60% increase in a proteoglycan subfraction that bound LDL with very high
      affinity. The incorporation of [3H]leucine into total cellular protein decreased
      significantly following exposure of smooth muscle cells to hypoxia as well as
      hypoxia/reoxygenation. These results indicate that hypoxia and
      hypoxia/reoxygenation cause major alterations in proteoglycan metabolism by
      vascular smooth muscle cells.

PMID- 10208489
TI  - Fine mapping of low-density lipoprotein receptor gene by genetic linkage on
      chromosome 19p13.1-p13.3 and study of the founder effect of four French Canadian
      low-density lipoprotein receptor gene mutations.
AB  - Familial hypercholesterolemia (FH) is one of the most common autosomal codominant
      diseases. FH is caused by mutations in the low-density lipoprotein receptor
      (LDLR) gene and is characterized by raised plasma LDL-cholesterol, tendon
      xanthomas, and premature coronary heart disease. The frequency of FH among French
      Canadians in northeastern Quebec is higher than in most other populations, 1:154
      vs. 1:500 due to high prevalence of few recurrent mutations in the LDLR gene. In
      the French Canadian population, 11 mutations in the LDLR gene have been found to
      occur in geographically diverse areas and account for > 90% of cases. We have
      first constructed a high-resolution genetic map to locate several highly
      polymorphic markers close to LDLR locus, thus providing the necessary tools to
      study the origin of the four most common mutations which account for
      approximately 80% of our FH patients. We have then genotyped five markers
      (D19S413, D19S865, D19S221, D19S914, D19S586) in 102 heterozygotes (38 del >
      15kb; 36 W66G; 16 C646Y; 12 E207K), two compound heterozygotes (del > 15kb/W66G;
      del > 15kb/C646Y) and seven homozygotes (three del > 15 kb; three W66G: one
      E207K) with FH unrelated to the first and second degree. We have found that
      patients bearing the same LDLR gene mutation carry a common haplotype at the LDLR
      locus although there is evidence for the early occurrence of a recombinational
      event between the LDLR and the D19S221 locus in the French Canadian patients
      bearing the W66G mutation. The fine mapping of LDLR gene close to several highly
      informative microsatellite markers provide fine mapping details of the LDLR
      region and additional tools for studies of association between plasma lipoprotein
      levels and LDLR gene.

PMID- 10208490
TI  - Contribution of receptor negative versus receptor defective mutations in the LDL
      receptor gene to angiographically assessed coronary artery disease among young
      (25-49 years) versus middle-aged (50-64 years) men.
AB  - Elevated plasma LDL-cholesterol (LDL-C) levels are associated with an increased
      risk of coronary artery disease (CAD). Familial hypercholesterolemia (FH), a
      monogenic trait due to mutations in the LDL-receptor (R) gene is characterized by
      raised plasma LDL-C levels and premature CAD. The aim of the present
      investigation, derived from the study of a population of 1465 unrelated men aged
      25 to 64 years, was to compare the expression of CAD assessed by coronary
      angiography in young (aged 25-49 years) versus middle-aged (50-64 years)
      heterozygous FH patients of French Canadian descent. Furthermore, the
      relationship of binding-defective versus receptor negative mutations in the LDL-R
      to premature CAD ( < 50 years) was examined and compared with men displaying a
      normal plasma lipoprotein-lipid profile. From the original study sample, a total
      of 100 men met the clinical criteria of heterozygous FH. Among them, 30 were
      carriers of a receptor negative mutation (deletion > 15 kb or point mutations
      Y468X or R329X) whereas 64 were carriers of a receptor defective mutation (W66G,
      E207K or C646Y). As expected, in both age groups (25-49 years vs. 50-64 years),
      carriers of a receptor negative mutation had higher plasma cholesterol and LDL-C
      levels than carriers of a defective allele or men with a normal plasma
      lipoprotein-lipid profile. In addition, the mean number of diseased vessels (with
      > 50% stenosis) was higher in men aged 50-64 years compared to those aged 25 49
      years. In the two age groups, FH patients were characterized by a higher number
      of stenosed coronary vessels than the normal phenotype group. Within each group
      (either receptor negative, receptor defective or normal phenotype) plasma
      cholesterol, LDL-C, HDL-C, triglyceride and apolipoprotein B levels were similar
      irrespective of age (25 49 years vs. 50-64 years). Finally, multiple logistic
      regression analyses revealed that compared to non-FH men, the relative odds of
      being affected by CAD before the age of 50 years was 7.3-fold higher for carriers
      of a receptor negative mutation and 2.7-fold higher for men with a receptor
      defective mutation at the LDL-R locus. These results suggest that CAD could be an
      earlier event among heterozygous FH subjects bearing a receptor negative mutation
      compared to LDL-R defective patients. It also suggest that the selective
      screening for mutations in the LDL-R gene may allow a better assessment of the
      individual risk and facilitate the development of family-based preventive
      strategies or intervention programs in FH.

PMID- 10208491
TI  - Genetic causes of mild hyperhomocysteinemia in patients with premature occlusive
      coronary artery diseases.
AB  - Elevated plasma homocysteine is increasingly being recognized as a risk factor
      for coronary artery disease (CAD). Although there is general agreement on the
      importance of micronutrients and genetic predisposition to elevated plasma
      homocysteine, the exact influence of the known prevalent mutations in genes which
      regulate homocysteine metabolism is not clear. We studied 376 cases of
      individuals with premature CAD with respect to their fasting and post-methionine
      load (PML) total homocysteine (tHcy) concentrations. We also determined the
      presence or absence of the T833C and G919A mutations of the cystathionine-beta
      synthase (CBS) gene, the C677T mutation of the methylene tetrahydrofolate
      reductase (MTHFR) gene, and the A2756G transition of the B12 dependent methionine
      synthase (MS) gene. Our objectives were therefore both to confirm the
      relationship of plasma homocysteine with premature CAD and to examine the
      importance of genetic influence on both fasting and PML homocysteine.
      Approximately 32% of the CAD patients had fasting hyperhomocysteinemia and 16%
      had PML hyperhomocysteinemia. Of these, 8.5% had both forms of
      hyperhomocysteinemia (combined hyperhomocysteinemia). The T133C mutation in the
      CBS gene and the thermolabile C677T mutation in the MTHFR gene seem to play an
      important role in the subset of individuals with combined hyperhomocysteinemia.
      The A2756G transition in the MS gene is not associated with elevated plasma tHcy.
      Many cases (47%) of hyperhomocysteinemia are not associated with micronutrient
      deficiencies, impaired renal function, and/or currently known genetic mutations.
      Further work is needed to study whether unknown mutations, particularly those
      residing in the intronic sequences of the genes involved in homocysteine
      metabolism, other environmental factors, or interaction of gene, nutrient, and
      environmental factors may be the cause of currently unexplained cases of mild
      hyperhomocysteinemia.

PMID- 10208492
TI  - Immunoscintigraphy of atherosclerotic uncomplicated lesions in vivo with a
      monoclonal antibody against D-dimers of insoluble fibrin.
AB  - To test the effectiveness of a new F(ab')2 monoclonal antibody against human
      fragment D-dimer of cross-linked fibrin in the detection of uncomplicated
      atherosclerotic lesions of the carotid vessel previously documented at echo-color
      Doppler and selective arteriographic study, 8 patients underwent a scintigraphic
      study including dynamic and early and delayed (3 h later) static imaging of the
      neck after injection of a bolus of 99mTc-labeled monoclonal antibody, and were
      subsequently operated. Vessel specimens and blood samples were drawn at operation
      and counted. No adverse reaction occurred after administration of the monoclonal
      antibody. The atherosclerotic lesion appeared as a focal area of asymmetrical
      tracer uptake, already visible at early images in four patients, and at delayed
      images in five. The average tracer uptake ratio between pathological and normal
      vessels was 1.40+0.24 (P < 0.05) at time-activity curves derived from dynamic
      images, 2.17+/-0.97 (P < 0.05) at early static images and 2.05+/-0.98 (P < 0.05)
      at delayed static images, respectively. Mean vessel to blood uptake rate of
      specimens obtained at operation was 2.22+/-0.59 (P < 0.001). The study shows that
      the 99mTc-labeled antibody was found to be safe and capable of detecting
      atherosclerotic plaques in humans.

PMID- 10208493
TI  - Combination of low-dose folic acid and pyridoxine for treatment of
      hyperhomocysteinaemia in patients with premature arterial disease and their
      relatives.
AB  - Hyperhomocysteinaemia is an independent risk factor for atherosclerotic disease
      and venous thrombosis. The optimal homocysteine-lowering vitamin dose and target
      total homocysteine (tHcy) concentration are currently unknown. We prospectively
      studied the homocysteine-lowering effect after 8 weeks low-dose combination of
      folic acid (0.5 mg) and pyridoxine (100 mg) in 49 hyperhomocysteinaemic persons
      (33 patients with documented premature arterial disease and 16 of their first
      degree relatives). Hyperhomocysteinaemia was in both sexes defined as fasting
      tHcy concentration > 12 micromol/l and/or post-methionine load tHcy concentration
      > 38 micromol/l. Low-dose vitamin therapy significantly reduced fasting tHcy
      concentration (median 13.9 to 9.3 micromol/l, reduction 32% (95% CI: 27-37%)) and
      post-load tHcy concentration (median 55.2 to 36.5 micromol/l, reduction 30% (95%
      CI: 25-35%)). Fasting tHcy reduction was similar in women and men, as well as in
      patients and relatives. Post-load tHcy reduction was significantly less in men
      compared to women (P = 0.04) and in relatives compared to patients (P = 0.03).
      Although low-dose combination of folic acid and pyridoxine results in a
      substantial reduction of tHcy concentrations (30-32%) in subjects with
      hyperhomocysteinaemia, the normalisation percentage to predefined criteria was
      less impressive (49%).

PMID- 10208494
TI  - Influence of mild to moderately elevated triglycerides on low density lipoprotein
      subfraction concentration and composition in healthy men with low high density
      lipoprotein cholesterol levels.
AB  - Epidemiologic studies have shown that a dyslipoproteinemia with low
      concentrations of high density lipoprotein (HDL) cholesterol and elevated serum
      triglycerides (TG) is associated with a particularly high incidence of coronary
      artery disease. This lipid profile is associated with increased concentrations of
      small, dense low density lipoprotein (LDL) particles. To evaluate the role of
      mild to moderately elevated TG on the LDL subfraction profile in patients with
      low HDL cholesterol, concentration and composition of six LDL subfractions was
      determined by density gradient ultracentrifugation in 41 healthy men (31+/-9
      years, body mass index (BMI) 25.1+/-3.9 kg/m2) with equally low HDL cholesterol
      levels < 0.91 mmol/l but different TG levels: TG < 1.13 mmol/l, n = 16; TG = 1.13
      2.26 mmol/l, n = 13: TG = 2.26-3.39 mmol/l, n = 12. Those men with moderately
      elevated TG levels between 2.26 and 3.39 mmol/l had significantly higher
      concentrations of very low density lipoprotein (VLDL), intermediate low density
      lipoprotein (IDL), and small, dense LDL apoB and cholesterol than men with TG <
      1.13 mmol/l. With increasing serum TG, the TG content per particle also increased
      in VLDL, IDL as well as total LDL particles while the cholesterol and
      phospholipid (PL) content decreased in VLDL and IDL, but not in LDL particles.
      LDL subfraction analysis revealed that only large, more buoyant LDL particles (d
      < 1.044 g/ml) but not the smaller, more dense LDL, were enriched in TG. Small,
      dense LDL particles were depleted of free cholesterol (FC) and PL. This study has
      shown that in men with low HDL cholesterol levels mild to moderately elevated
      serum TG strongly suggest the presence of other metabolic cardiovascular risk
      factors and in particular of a more atherogenic LDL subfraction profile of
      increased concentration of small, dense LDL particles that are depleted in
      surface lipids.

PMID- 10208495
TI  - Vitamin E ingestion does not improve arterial endothelial dysfunction in older
      adults.
AB  - Endothelial dysfunction is thought to be an important early event in
      atherogenesis, related in part to reduced bioavailability of nitric oxide in the
      arterial wall. Endothelial function may be impaired in the presence of oxidised
      low density lipoprotein. The use of vitamin E as an anti-oxidant might enhance
      the bioavailability of nitric oxide in this situation. The effect of vitamin E
      1000 IU/day on arterial endothelial physiology was studied in 20 asymptomatic
      older subjects, aged 45-70 years, who showed evidence of age-related endothelial
      dysfunction. Endothelial function was assessed non-invasively using brachial
      ultrasound and the primary outcome measure was flow-mediated endothelium
      dependent dilatation (FMD) in response to reactive hyperaemia. A double-blind,
      placebo-controlled, randomised crossover design was employed. After 3 weeks of
      stabilisation on a standard fat-reduced diet, subjects received vitamin E or
      placebo for 10 weeks in random order, separated by a washout period of 8 weeks.
      There were no significant changes in blood pressure, plasma lipid or lipoprotein
      concentrations. Plasma alpha-tocopherol increased from 50+/-3 (mean+/-S.E.M.) to
      91+/-6 micromol/l (P < 0.001) with vitamin E ingestion. Total plasma F2alpha
      isoprostanes, a measure of free radical-induced lipid peroxidation, were not
      altered by vitamin E ingestion (0.86+/-0.26 versus 0.82+/-0.25 nmol/l, P > 0.6).
      FMD was not significantly different between the placebo and vitamin E periods
      (2.7+/-0.6% versus 2.4+/-0.4%). Variation in FMD was not correlated with change
      in plasma alpha-tocopherol (r = - 0.03, P > 0.8). The study was powered to detect
      a minimum change in FMD of 2%. Glyceryl trinitrate endothelium-independent
      dilatation was not significantly changed with vitamin E (13.7+/-1.3% versus
      13.6+/-1.4%,). These results exclude a major impact of medium-term
      supplementation with vitamin E on arterial endothelial function when age-related
      dysfunction is already present.

PMID- 10208496
TI  - Burst production of superoxide anion in human endothelial cells by
      lysophosphatidylcholine.
AB  - This study examined whether lysophosphatidylcholine (lysoPC), an atherogenic
      lipid, may stimulate production of O2*-, in cultured human endothelial cells.
      Production of O2*- was detected by bis-N-methylacridinium nitrate (lucigenin)
      elicited chemiluminescence. LysoPC was found to induce burst production of O2*-,
      peaked at 2-4 min after the stimulation, in intact endothelial cells. LysoPC also
      stimulated NADH-dependent production of O2*- in particulate fraction of the
      cells, and the action of lysoPC was inhibited by diphenyliodonium. The results
      suggested that lysoPC stimulated production of O2*- partly through membrane
      associated NADH-dependent O2*- production systems.

PMID- 10208498
TI  - Detection of structural alterations in LDL isolated from type 2 diabetic
      patients: application of the fructosamine assay to evaluate the extent of LDL
      glycation.

PMID- 10208497
TI  - Absence of CC chemokine receptor-2 reduces atherosclerosis in apolipoprotein E
      deficient mice.
AB  - The accumulation of circulating monocytes in the arterial wall is an early event
      in atherosclerotic plaque formation. Monocyte chemoattractant protein-1 (MCP-1)
      has been implicated as the primary source of monocyte chemoattractant functioning
      in these early stages of atherogenesis. To determine whether the receptor for MCP
      1, CC chemokine receptor CCR2, plays a role in atherogenesis, CCR2-deficient
      animals were crossed with mice lacking apo E, a well characterized model of
      atherosclerosis. While lipid levels were unchanged, the double knockout mice
      exhibited a 3-fold reduction in mean aortic lesion area compared to apo E
      deficient control mice. Furthermore, the lesions in the double mutants were less
      advanced, consisting primarily of foam cell deposits and fatty streaks located on
      or directly adjacent to the aortic valve attachment sites. These studies directly
      demonstrate that the MCP-1 receptor, CCR2, plays an important role in
      atherogenesis.

PMID- 10208499
TI  - Association of 1617 C --> T genetic variation in exon 11 of human low-density
      lipoprotein receptor and plasma lipid concentration.

PMID- 10208500
TI  - Atorvastatin in the management of an index patient with complete hepatic lipase
      deficiency.

PMID- 10208501
TI  - LDL-apheresis improves microalbuminuria in patients with severe familial
      heterozygous hypercholesterolemia.

PMID- 10208502
TI  - Classification criteria for skin-sensitizing chemicals: a commentary.
AB  - A formalized, standardized and effective mechanism for the identification of
      substances which possess significant skin sensitization potential is a necessary
      first step in the process of limiting the incidence of allergic contact
      dermatitis. Strategies to achieve such hazard identification are unified
      throughout the European Union and also have been publicised by the World Health
      Organization. Global harmonization of these and other approaches (e.g., in the
      USA) is being driven by the Organization for Economic Cooperation and
      Development. In this paper, the benefits and limitations of these classification
      systems are reviewed. A common element of all the systems is that they seek to
      distinguish important contact allergens from chemicals which are infrequent
      sensitizers. The European criteria are legal requirements in the EU member states
      and formal classification as a skin sensitizer leads to mandatory labelling. The
      most notable omission from current and proposed classification criteria relates
      to the relative potency of a classified skin sensitizer and the exposure dose.
      Such information is necessary for proper risk assessment and management measures
      to be implemented.

PMID- 10208503
TI  - Regulatory classification of substances oxidized to skin sensitizers on exposure
      to air.
AB  - Regulatory classification of substances in the European Union (EU) is intended to
      identify their hazardous toxicological properties in a formal and harmonized
      manner. In the regulatory work, a specific chemical with its molecular structure
      is classified as a skin sensitizer. This implies that the compound is stable
      throughout its lifetime. The purpose of the present paper is to discuss the
      problem of skin sensitizing oxidation/degradation products formed by air exposure
      of various materials or substances with very low allergenic activity. In
      regulatory classification work on skin sensitizers, the intrinsic suspectibility
      of a chemical to air oxidation (autoxidation) should be taken into consideration.
      We give examples of natural terpenoid materials, but the concept of allergens
      formed by air oxidation can apply to other materials widely used in industrial
      products. If a positive classification is made for a substance with a known
      chemical structure, a note should indicate that the primary chemical structure of
      the notified substance is not a skin sensitizer, but that (some of) its oxidation
      products are. Complex mixtures which inevitably contain sensitizing oxidation
      products should (on the basis of sufficient evidence) be classified as skin
      sensitizing.

PMID- 10208504
TI  - Squamometry: an evaluation method for a barrier protectant (tannic acid).
AB  - Squamometry for evaluating skin barrier substances is described. Forearms of 8
      volunteers were dosed with 0, 0.25, 0.5, and 1% sodium lauryl sulfate (SLS) in
      distilled water (semi-open method) for 24 h, to skin pretreated with distilled
      water and 5% tannic acid, a model barrier protectant. Squamometric evaluation
      indicated the skin damage increased with SLS concentration in a dose-dependent
      manner, and that tannic acid reduced the damage (p<0.01). The results suggest
      that squamometry may be a useful method for determining efficacy of skin barrier
      substances.

PMID- 10208505
TI  - Frequency of contact allergy in children with atopic dermatitis: results of a
      prospective study of 137 cases.
AB  - The aim of our study was the evaluation of contact sensitization in pediatric
      patients with atopic dermatitis (AD). It seems that the frequency of contact
      allergies in the course of AD, and also the frequency of contact allergies in
      children, is underestimated in general. Our study has been performed by
      investigating 137 children with AD. The childrens' history was taken according
      standardized consultation guidelines and followed by a physical examination.
      Patch testing was performed systematically, including the European standard
      series, together with tixocortol pivalate, budesonide and the applied emollient.
      If necessary, optional patch tests were performed according to the child's
      history. The results demonstrate contact sensitization in 43% of all children
      tested. The most frequent contact allergens are: metals (19.3%), fragrance
      (4.4%), balsam of Peru (2.6%), lanolin (4.4%), neomycin (2.6%) and emollients
      (2.6%). No contact sensitization to corticosteroids nor any induction of active
      sensitization were seen. Statistical analysis demonstrates that the risk of
      developing a contact allergy is significantly elevated in children after the age
      of 5 years. Female sex is a risk factor only for nickel. Age of onset of AD or
      its severity is not associated with the development of contact allergy. In
      conclusion, the results indicate the necessity of performing systematic patch
      testing in the investigation of allergies in children with AD. Preventive
      measures from an early age are suggested to avoid exposure to the most frequent
      contact allergens.

PMID- 10208506
TI  - Identification of coumarin as the sensitizer in a patient sensitive to her own
      perfume but negative to the fragrance mix.
AB  - The aim of this study was to identify the chemicals responsible for the
      sensitivity of a 44-year-old woman to her own perfume, but showing negative patch
      test results to the fragrance mix. For this purpose, the perfume concentrate from
      the eau de toilette was chemically fractionated. Each fraction obtained was
      afterwards tested on the patient using a ROAT and/or a patch test. Only 1
      fraction gave a positive ROAT result. This fraction was analyzed and found to
      contain coumarin and ethyl vanillin. Coumarin, one of the most widely used
      fragrance compounds that is not present in the fragrance mix, was confirmed as
      being the sensitizer.

PMID- 10208508
TI  - In vivo nickel allergic contact dermatitis: human model for topical therapeutics.
AB  - Techniques to determine efficacy of topical agents on allergic contact dermatitis
      (ACD) may benefit from refinement. The aim of this study was to develop an in
      vivo human model system for the bioengineering and visual quantification of the
      effect of topical agents on nickel ACD, and to correlate ACD parameters. 14
      nickel patch-test-positive subjects were included in a placebo-controlled, double
      blind study after a pre-screening procedure with a standard diagnostic patch test
      with nickel sulfate in 54 healthy human volunteers. 5% nickel sulfate in
      petrolatum in a Finn Chamber was applied on forearm skin for 48 h to create a
      standardized dermatitis. Thereafter, the dermatitis was treated with a model
      topical agent and a placebo control while recording endpoint parameters daily for
      10 days. Resolution was quantified with 4 parameters: visual scoring (VS),
      transepidermal water loss (TEWL) (Tewameter), skin blood flow volume (BFV) (laser
      Doppler flowmeter), and skin color (a* value) (Colorimeter). The model agent
      reduced cutaneous allergic reactions, especially on day 8 to 10, in comparison
      with the placebo control. A highly significant linear relationship exists among
      all parameters, except between a* and BFV. This model may provide robust
      biometrics for determining the efficacy of topical therapeutics on experimentally
      induced ACD.

PMID- 10208507
TI  - The flare-up reactions after systemic provocation in contact allergy to nickel
      and gold.
AB  - In a controlled double-blind experimental study, patients with contact allergy to
      nickel or gold were exposed systemically to their contact allergen. Nickel
      sulfate was given orally, gold sodium thiomalate intramuscularly, and placebo by
      both routes. Clinical reactions including body temperature were followed and 7
      plasma cytokines and acute phase reactants were assayed before and 24 h after
      provocation. Clinical flare-up, with reactivation of healing patch tests and/or
      toxicoderma-like reactions, was observed in patients receiving their specific
      allergen. A transient fever was noted in patients allergic to gold when exposed
      to gold, not in others. There was a significant increase in plasma tumour
      necrosis factor-alpha, soluble tumour necrosis factor receptor 1, interleukin-1
      receptor antagonist, and neutrophil gelatinase associated lipocalin in patients
      allergic to gold when exposed to gold allergen. Furthermore, in patients allergic
      to nickel exposed to nickel allergen there was a highly significant increase in
      plasma soluble tumour necrosis factor receptor 1. Interferon-gamma, interleukin
      4, and C-reactive protein did not increase in any of the patient groups. Clinical
      reactions during flare-up in contact allergy are accompanied by release in the
      blood of several cytokines. This release is not a consequence of a toxic effect
      or bound to a particular allergen. Instead, the cytokine release should be
      considered a general phenomenon characteristic of the flare-up in contact
      allergy.

PMID- 10208509
TI  - The allergens of Dendropanax trifidus Makino and Fatsia japonica Decne. et
      Planch. and evaluation of cross-reactions with other plants of the Araliaceae
      family.
AB  - cis-9,17-Octadecadiene-12,14-diyne-1,16-diol (I), an analog of falcarinol has
      been identified in our previous report as an active component of Dendropanax
      trifidus and a strong sensitizer. In this report, 16-hydroxy-cis-9,17
      octadecadiene-12,14-diynoic acid (II) and cis-9,trans-16-octadecadiene-12,14
      diynoic acid (III) were elucidated as 2 other active components of the plant.
      Compound I, however, presented with the highest concentration and showed a
      stronger reaction on patch testing. The leaves of Fatsia japonica Decne. et
      Planch. were also found to contain compound I, but the amount was found to be 7x
      more in Dendropanax trifidus than in Fatsia japonica. 5 subjects with
      hypersensitivity to Dendropanax trifidus and compound I showed positive reactions
      when patch tested with the leaves of Hedera helix L. and Schefflera arboricola. 1
      of these also showed a positive reaction to the extract of Panax ginseng root
      powder diluted 1% in ethanol. There was cross-reaction among these plants, which
      all belong to the Araliaceae family.

PMID- 10208510
TI  - Allergic contact dermatitis from doxepin.

PMID- 10208511
TI  - Azo dyes as allergens in carbonless copy paper manufacturing.

PMID- 10208512
TI  - Anaphylactic shock after application of chlorhexidine to unbroken skin.

PMID- 10208513
TI  - Lymphomatoid eosinophilic reaction to gold earrings.

PMID- 10208514
TI  - Nickel in "nickel-free" spectacle frames.

PMID- 10208515
TI  - Severe contact allergy to footwear responding to handmade shoes.

PMID- 10208516
TI  - Merbromine-induced pustular contact dermatitis.

PMID- 10208517
TI  - Nickel allergy in a trumpet player.

PMID- 10208518
TI  - Fixed drug eruptions due to betalactams and other chemically unrelated
      antibiotics.

PMID- 10208519
TI  - Occupational hand dermatitis due to 1,2-benzisothiazolin-3-one in the water
      softener manufacturing industry.

PMID- 10208520
TI  - Allergic contact dermatitis from furaltadone in eardrops.

PMID- 10208521
TI  - Airborne photocontact dermatitis due to the pesticides maneb and fenitrothion.

PMID- 10208522
TI  - Occupational dermatitis in Sheffield: a preliminary study.

PMID- 10208523
TI  - Allergic contact dermatitis associated with photosensitivity, from alantolactone
      in a chrysanthemum farmer.

PMID- 10208524
TI  - Dermal contact dermatitis caused by allergy to palladium.

PMID- 10208525
TI  - A 15-year review of our MOAHLFA index.

PMID- 10208526
TI  - Occupational contact dermatitis from acrylic monomer in paint.

PMID- 10208527
TI  - Macrophage secretory products influence the survival of statoacoustic neurons.
AB  - Prior studies have shown that macrophages are recruited to sites of injury or
      infection in the sensory organs of the inner ear, but the effects of macrophages
      and their cytokine secretory products on the sensory structures of the ear are
      not known. In the present study, cultures of dissociated statoacoustic neurons
      were incubated with selected macrophage secretary products and the numbers of
      surviving neurons after 48 h in vitro were quantified. Results indicate that two
      macrophage secretary products, interleukin 1 and fibroblast growth factor 2, can
      enhance the survival of statoacoustic neurons, while another cytokine, tumour
      necrosis factor-alpha can diminish the survival of those neurons. Also, numerous
      macrophages were present in both cytokine-treated and control cultures. The
      findings suggest that macrophages may influence the survival of the sensory
      neurons of the inner ear.

PMID- 10208528
TI  - Hyper- and hypogravity alter posture in rats compensated on Earth for a
      vestibular asymmetry.
AB  - Head posture and neck muscle activity (EMGs) were examined in unilateral (UL) and
      bilateral (BL) vestibularly lesioned rats in hypergravity (1.7 g) and hypogravity
      (0 g) during parabolic flights. Compared with BL rats taken as control, the head
      and the body of UL deviated toward the lesion side at 0 g and toward the intact
      side at 1.7 g. Recorded in head fixed condition, left and right EMGs remained
      symmetrical in BL while UL rats displayed an asymmetry between left and right
      muscles at 1.7 g, but not at 0 g. These results demonstrate that an experimental
      otolithic asymmetry, compensated on Earth, can become unbalanced in altered
      gravity. Paradoxically, the utricular system appears to play a major role in that
      process.

PMID- 10208529
TI  - Medial prefrontal cortex generates frontal midline theta rhythm.
AB  - Frontal midline theta rhythm (Fm theta) is a distinct theta activity of EEG in
      the frontal midline area that appears during concentrated performance of mental
      tasks in normal subjects and reflects focused attentional processing. To
      tomographically visualize the source current density distributions of Fm theta,
      we recorded Fm theta by using a 64-channel whole-head MEG system from four
      healthy subjects, and applied a new analysis method, synthetic aperture
      magnetometry (SAM), an adaptive beam forming method. Fm theta was observed in the
      MEG signals over the bilateral frontal regions. SAM analysis showed bilateral
      medial prefrontal cortices, including anterior cingulate cortex, as the source of
      Fm theta. This result suggests that focused attention is mainly related to medial
      prefrontal cortex.

PMID- 10208530
TI  - Complete mutism after midbrain periaqueductal gray lesion.
AB  - Several neurophysiological studies have highlighted the role of the midbrain
      periaqueductal gray matter (PAG) in the initiation of vocalization in various
      animal species, from frogs to primates. With regard to humans, only two cases of
      complete mutism following a lesion to the PAG have been reported so far. This
      article describes a new case of a patient (GM) who, following an ischemic lesion
      to the periaqueductal gray region of the midbrain, presented with complete and
      irreversible mutism, though her language comprehension functions and her non
      verbal expression capacity were preserved. This clinical case provides evidence
      that in humans the PAG also acts as a link between different vocalization
      eliciting external and internal stimuli (which reach the PAG from sensory and
      emotional structures) and the vocal-motor coordinating mechanisms in the lower
      brain stem.

PMID- 10208531
TI  - Striatal A2A adenosine receptors differentially regulate spontaneous and K+
      evoked glutamate release in vivo in young and aged rats.
AB  - The effect of the adenosine A2A receptor agonist CGS 21680 on glutamate and
      aspartate release was investigated in the striatum of young and old rats by
      microdialysis experiments. CGS 21680 (10 microM) significantly increased
      glutamate and aspartate spontaneous outflow in young but not in old rats. On the
      contrary, CGS 21680 induced the same decrease in K+-evoked glutamate outflow in
      both young and aged rats. A lower dose of CGS 21680 (1 microM) failed to modify
      either spontaneous or K+-evoked outflow. It is suggested that the opposite
      effects of the A2A agonist on excitatory amino acid outflow may be respectively
      mediated by striatal A2A adenosine receptors located on glutamatergic terminals
      and on the striatal indirect output pathway.

PMID- 10208533
TI  - Nicotine withdrawal in the rat: role of alpha7 nicotinic receptors in the ventral
      tegmental area.
AB  - Previous data show that nicotinic receptors in the ventral tegmental area are of
      importance for the nicotine withdrawal syndrome. Here we have investigated the
      specific role of alpha7 nicotinic receptors in the ventral tegmental area for the
      neurobiological and behavioral consequences of nicotine withdrawal. Rats were
      exposed to nicotine for 14 days via s.c. osmotic minipumps. Bilateral
      intrategmental injections of the selective alpha7 nicotinic receptor antagonist
      methyllycaconitine reduced locomotion in the nicotine-treated rats, but not in
      control animals. Unilateral intrategmental injection of methyllycaconitine
      reduced dopamine output in the ipsilateral nucleus accumbens of nicotine-treated
      rats, but not in controls. Our results indicate that alpha7 nicotinic receptors
      in the ventral tegmental area are involved in the nicotine withdrawal syndrome.

PMID- 10208532
TI  - (+/-)Cyclazocine blocks the dopamine response to nicotine.
AB  - (+/-)Cyclazocine, synthesized by Archer in 1962, was originally tested as a
      treatment for heroin addiction. (+/-)Cyclazocine is a mu opioid antagonist and
      kappa opioid agonist, and because of these actions, would be expected to modulate
      dopamine release in the nucleus accumbens as well as the reinforcing effects of
      drugs of abuse. In a recent study (+/-)cyclazocine was reported to decrease
      cocaine self-administration in rats. The aim of the present study was to
      determine whether (+/-)cyclazocine would alter the dopaminergic effects of
      nicotine that are thought to mediate its rewarding effects. Using in vivo
      microdialysis in awake and freely moving rats, we investigated the effect of (+/
      )cyclazocine (0.5 mg/kg, i.p.) on the acute dopamine response to nicotine (0.32
      mg/kg, i.v. over a 5 min period, infused 30 min later) in the nucleus accumbens.
      (+/-)Cyclazocine significantly attenuated the increase in extracellular dopamine
      levels induced by the nicotine infusion and enhanced nicotine-induced increases
      in dopamine metabolites. (+/-)Cyclazocine alone did not significantly affect
      extracellular dopamine levels. However, both the (+) and (-) enantiomers of
      cyclazocine did alter basal dopamine levels and these effects made it difficult
      to assess their individual interactions with nicotine. The results suggest that
      the effects of both enantiomers contribute to the effects of the racemate; (+/
      )cyclazocine may decrease the rewarding effect of nicotine and may be the
      prototype of a potentially novel treatment for smoking.

PMID- 10208534
TI  - Enhancement of TNF-alpha production by ganglioside GM2 in human mononuclear cell
      culture.
AB  - Some gangliosides have been regarded as autoantigens of immune-mediated
      neurological disorders such as Guillain-Barre syndrome (GBS), Miller Fisher
      syndrome and multifocal motor neuropathy. On the other hand, proinflammatory
      cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma
      (IFN-gamma), may be important in the pathogenesis of some neuroimmunological
      disorders. To clarify the interactions between immune cells and gangliosides, we
      investigated the effects of gangliosides on the production of proinflammatory
      cytokines in peripheral blood mononuclear cell (PBMC) cultures. We found that
      ganglioside GM2 markedly enhances the production of TNF-alpha and that TNF-alpha
      induction by coated GM2 is still more marked. These findings suggest that immune
      cells, especially monocytes/macrophages, cause inflammation upon encountering
      GM2.

PMID- 10208535
TI  - Long-term administration of MC4 receptor antagonist HS014 causes hyperphagia and
      obesity in rats.
AB  - In this study we investigated the long term effects of a potent and selective
      melanocortin 4 (MC4) receptor antagonist (HS014) on food intake, body weight,
      body composition and blood glucose levels in adult rats. HS014 was injected
      i.c.v. either by twice-daily injections (2 x 1 nmol) for 6 days or administered
      by continuous infusion with osmotic minipumps (0.16 nmol/h) for 2 weeks. The
      results show a considerable increase in food intake and body weight after both of
      the treatments without any signs of tachyphylaxis. After 2 weeks of treatment
      with osmotic pumps, the HS014-treated rats (average weight 425g) had 20% higher
      body weight than the controls rats (average 360 g). When i.c.v. injections were
      terminated, the body weight of the twice-daily HS014-treated rats returned to the
      levels of control group, whereas the rats treated with continuous infusion of
      HS014 remained hyperphagic and still gained weight. Blood glucose levels in the
      rats treated with HS014 infusion were significantly increased. Analysis of body
      composition in HS014-infused rats indicated that body weight was increased due to
      fat deposits. These data show for the first time that chronic administration of
      exogenous MC4 receptor antagonist causes hyperphagia and severe obesity in rats.
      These data also indicate that the melanocortic control of food intake is very
      robust and suggest that changes induced by such treatment overcome negative
      feedback signals.

PMID- 10208536
TI  - Effects of consciousness on human brain waves following binocular rivalry.
AB  - When the two eyes of an observer are exposed to conflicting stimuli, they enter
      into binocular rivalry and the two possible percepts will alternate in dominance.
      We investigated neural activity and its time course following binocular rivalry
      by measuring human event-related brain potentials to transitions from rivalrous
      to non-rivalrous stimulation. When these changes did not entail a change in
      conscious perception they elicited a markedly attenuated N1 component and a
      delayed and attenuated P3 peak as compared to percept-incompatible changes and
      non-rivalrous control conditions. These results suggest that in humans binocular
      rivalry is resolved at latest in extrastriate visual areas.

PMID- 10208537
TI  - Oxidative stress induces amyloid-like aggregate formation of NACP/alpha-synuclein
      in vitro.
AB  - The precursor of non-amyloid beta protein component of Alzheimer's disease
      amyloid (NACP/alpha-synuclein), found in Lewy bodies of Parkinson's disease (PD),
      is a presynaptic protein genetically linked to some familial types PD. Mechanisms
      of abnormal NACP/alpha-synuclein aggregation in neurodegenerative diseases are
      unclear. Since oxidative stress might play a role in PD pathogenesis, we
      investigated the role of iron and peroxide in NACP/alpha-synuclein aggregation.
      Immunoblot analysis showed that human NACP/alpha-synuclein (but not beta
      synuclein) aggregated in the presence of ferric ion and was inhibited by the iron
      chelator deferoxamine. Ferrous ion was not effective by itself, but it
      potentially aggregated NACP/alpha-synuclein in the presence of hydrogen peroxide.
      NACP/ alpha-synuclein aggregates displayed strong thioflavine-S and congo-red
      reactivity, reminiscent of amyloid. This study suggests that NACP/alpha-synuclein
      aggregation might be closely related to oxidative reactions which may play a
      critical role in neurodegeneration in disorders with Lewy bodies.

PMID- 10208538
TI  - Microglial cells respond to amyloidogenic PrP peptide by the production of
      inflammatory cytokines.
AB  - The scrapie isoform of the prion protein (PrPres) induces neurodegeneration and
      gliosis in the central nervous system. These features may be reproduced in vitro
      on exposure of neuronal and glial cultures to PrPres and the peptide HuPr P106
      126. In the present study, we investigated the role of microglial cells and
      astrocytes in the pathological process by studying their molecular response to
      PrP 106-126 exposure. PrP 106-126 elicited a specific overproduction of pro
      inflammatory cytokines IL1beta and IL6 in microglial cells (but not increased
      expression of TNFalpha, IL10, and TGFbeta1) and over-expression of GFAP in
      astrocytes. These effects were strictly dependent on the ability of the peptide
      to form amyloid fibrils. These data strongly suggest that microglial cells
      contribute to prion-related neurodegenerative processes by producing
      proinflammatory cytokines in the brain areas of amyloid PrP deposition.

PMID- 10208539
TI  - Cardiovascular effects produced by nitric oxide-related drugs in the caudal
      ventrolateral medulla.
AB  - The role of nitric oxide in the central control of blood pressure was evaluated
      by interfering with its local formation in the caudal region of the ventrolateral
      medulla (CVLM). Urethane anesthetized male Wistar rats were used. Microinjection
      of L-arginine (L-Arg, 25-100 nmol) produced a hypertensive effect without
      significant changes in heart rate (HR). Microinjection of N(G)-nitro-L-arginine
      methyl ester (L-NAME, 7.4 nmol) produced a significant hypotensive effect.
      Microinjection of L-Arg (50 nmol) combined with L-NAME (7.4 nmol) did not
      significantly change mean arterial pressure or HR. A similar finding was obtained
      with microinjection of L-Arg (50 nmol) 5 min after microinjection of methylene
      blue (5 nmol) into the CVLM. The pressor effect of L-Arg was also abolished by
      prior i.v. injection of a vasopressin V1 receptor antagonist, but not by prior
      i.v. injection of prazosin. These results suggest an inhibitory role for local NO
      in the CVLM and that nitrergic pathways at the CVLM participate in the central
      regulation of AVP release.

PMID- 10208540
TI  - 3-Dimensional visualization of lesions in rat brain using magnetic resonance
      imaging microscopy.
AB  - High-resolution (< 50 microm) magnetic resonance imaging microscopy (MRM) has
      been used to identify brain regions and localization of excitotoxin-induced
      lesions in fixed rat brains, subsequently confirmed using standard histology. The
      anatomical extent of lesions identified by MRM was identical to that seen in
      histological sections and various histopathological changes could be visualized.
      In contrast to the time involved in preparing and examining histological
      sections, lesions in intact brains could be rapidly identified and visualized in
      three dimensions by examining digitally generated sections in any plane. This
      study shows that MRM has tremendous potential as a prescreening tool for
      neurotoxicity and neuropathology. These observations suggest that MRM has the
      potential to affect pathology much as conventional MRI has influenced clinical
      imaging.

PMID- 10208541
TI  - A gustatory cyclic nucleotide-gated channels CNGgust, is expressed in the retina.
AB  - Cyclic nucleotide-gated (CNG) channels are essential proteins that contribute to
      the intracellular signal transduction of the senses of sight and smell. Recently,
      we found a novel CNG channel (CNGgust) in rat taste buds, and demonstrated its
      possible involvement in taste signal transduction. In the present study, we used
      RT-PCR and immunostaining to prove that this gustatory CNG channel is expressed
      in the outer segments of rat cone photoreceptor cells. The study strongly
      suggests that the senses of taste and sight share, at least in part, a common
      signal transduction pathway.

PMID- 10208542
TI  - Activity-dependent Nurr1 and NGFI-B gene expression in adult mouse olfactory
      bulb.
AB  - Previous studies showed that Nurr1 is essential to development of the dopamine
      phenotype in midbrain, but not for dopaminergic neurons intrinsic to the
      olfactory bulb (OB). The current study investigated the distribution of Nurr1 and
      NGFI-B as well as a role for both of these related orphan receptors in tyrosine
      hydroxylase (TH) expression in OB. Both NGFI-B and Nurr1 mRNAs were found in the
      glomerular and granule cell layers of OB. In contrast, only Nurr1 occurred in
      midbrain dopamine neurons. Both receptors as well as TH exhibited down-regulation
      in OB in response to odor deprivation produced by unilateral naris closure. These
      data suggest that in OB, both Nurr1 and NGFI-B may participate in development and
      regulation of the dopamine phenotype.

PMID- 10208543
TI  - Sensing of cadmium and copper ions by externally exposed ADL, ASE, and ASH
      neurons elicits avoidance response in Caenorhabditis elegans.
AB  - We developed a quantitative assay for Caenorhabditis elegans avoidance behavior.
      This was then used to demonstrate that the worm moved away from toxic
      concentrations of Cd2+ and Cu2+, but not Ni2+, all ions that prevented
      development from larval to adult stages. Mutants that have structural defects in
      ciliated neurons (che-2 and osm-3) as well as worms with three laser-operated
      neurons (ADL, ASE, and ASH), showed no avoidance behavior from Cd2+ and Cu2+.
      These results suggest that the avoidance from Cd2+ and Cu2+ are mediated through
      multiple neural pathways including ADL, ASE, and ASH neurons. We hypothesize that
      the three sensing neurons provide increased accuracy of the sensory response and
      a survival advantage in the natural environment of the worm.

PMID- 10208544
TI  - Lesion-remote metabolic changes after neocortical cold injury in rats.
AB  - Lesion-remote metabolic changes were examined 1-7 days after neocortical cold
      injury using tissue ATP, glucose and lactate bioluminescent imaging, pH-dependent
      fluoroscopy and cerebral protein synthesis (CPS) autoradiography. One day after
      lesioning an alkaline pH shift (0.35 +/- 0.19 units above contralateral) was
      noticed in the lesion-remote cortex, the underlying white matter, the striatum,
      hippocampus and thalamus, which slowly resolved within 7 days and probably
      reflected the spread of vasogenic edema. Closely associated with the pH shift,
      elevations in tissue glucose and lactate levels were found, which reached maximum
      levels after 3 days (7.4 +/- 2.4 vs 4.2 +/- 1.2 micromol/g glucose, 6.6 +/- 2.3
      vs 2.1 +/- 0.6 micromol/g lactate) but, in contrast to the alkalosis, remained
      elevated after 1 week. Thus, neocortical trauma is associated with long-lasting
      metabolic changes, which are intimately linked with the distribution of post
      traumatic alkalosis.

PMID- 10208545
TI  - Motor planning center for speech articulation in the normal human brain.
AB  - In order to locate the coordination center of speech movements in the dominant
      hemisphere of the normal human brain, we measured magnetoencephalographic (MEG)
      signals from the left frontal area of right-handed subjects while they pronounced
      different words. A broad response appeared during a period of 120-320 ms before
      the onset of speech sound, and its current dipole sources were localized on the
      magnetic resonance images in a region around the superior end of the left insula.
      Further, the onset of the MEG response preceded by about 100 ms the perioral
      muscle activities that occurred for the articulation in speaking the words. These
      results suggest that the deep frontal region is involved in the articulatory
      programming of speech movements.

PMID- 10208546
TI  - Does the pineal gland play a role in neuroendocrine fear responses?
AB  - The pineal gland secretes melatonin under an influence of suprachiasmatic nucleus
      neurones. Pinealectomy or melatonin administration affects behavioural responses
      to novel stimuli. Fear or novel stimuli inhibit vasopressin (VP) and facilitate
      oxytocin (OT) or prolactin (PRL) release from the pituitary. Thus the
      suprachiasmatic nucleus-pineal gland system may modulate VP, OT and PRL responses
      to conditioned fear stimuli. In the present experiments with male rats,
      pinealectomy or melatonin administration did not significantly change VP, OT or
      PRL responses to conditioned fear stimuli. Electrolytic lesions of the
      suprachiasmatic nuclei impaired VP but not OT or PRL responses. The results show
      that the pineal gland is not involved in neuroendocrine responses to conditioned
      fear stimuli and suggest that the suprachiasmatic nucleus is necessary for the VP
      response to fear stimuli.

PMID- 10208547
TI  - Brief predator odour exposure activates the HPA axis independent of locomotor
      changes.
AB  - Although predator exposure has been proposed to elicit both behavioural responses
      and neuroendocrine effects in rodents, results of an increasing number studies
      have failed to consistently detect both of these alterations. We provide a
      detailed multivariate quantitative assessment of locomotor activity levels and
      plasma levels of adrenocorticotrophic hormone (ACTH) and corticosterone of male
      and female laboratory rats following brief (5 min) exposure to a predator odour,
      (2-propylthietane, the main constituent of weasel anal gland secretion). We show
      that there is a clear distinction between the behavioural and neuroendocrine
      responses, with predator odour inducing significant increases in corticosterone
      and ACTH levels without any significant accompanying changes in various locomotor
      activity measures.

PMID- 10208548
TI  - Monitoring of anaesthesia in neurophysiological experiments.
AB  - Cortical activity can be substantially changed by the type of anaesthetic used,
      and by its dose level. For easy monitoring of depth of anaesthesia we describe
      the changes in electroencephalogram and electrocardiogram accompanying changes in
      depth of anaesthesia in the cat. Anaesthesia was induced by the volatile
      anaesthetic isoflurane. The high-frequency components (around 30 Hz) in the
      electroencephalogram disappear in deep anaesthesia. The electrocardiogram also
      shows substantial changes in contamination due to muscle fasciculations with
      anaesthesia level. Fasciculations appear as noise in the electrocardiogram. The
      amplitude of the electrical muscle activity contaminating the ECG can be easily
      used for the maintainance of a constant level of anaesthesia during a
      neurophysiological experiment.

PMID- 10208549
TI  - Effects of bis(7)-tacrine, a novel anti-Alzheimer's agent, on rat brain AChE.
AB  - The anticholinesterase effects of bis(7)-tacrine were compared with tacrine in
      vitro and in vivo. Based on IC50 ratios, the dimeric analog bis(7)-tacrine was,
      in a reversible manner, up to 150-fold more potent and 250-fold more selective
      than tacrine for acetylcholinesterase (AChE) over butyrylcholinesterase (BChE).
      Following a single oral administration, both bis(7)-tacrine and tacrine produced
      dose-dependent inhibitions of AChE in rat brain, but bis(7)-tacrine exhibited
      higher efficacy and AChE/BChE selectivity than tacrine. The anti-AChE efficacy of
      bis(7)-tacrine was quite similar following an oral or i.p. administration, but
      tacrine showed much lower efficacy when administered orally than when given i.p.
      These findings suggest bis(7)-tacrine, a highly potent and selective inhibitor of
      AChE, can probably be used as an improved drug in the palliative treatment of AD.

PMID- 10208550
TI  - Bis(7)-tacrine, a novel dimeric AChE inhibitor, is a potent GABA(A) receptor
      antagonist.
AB  - Heptylene-linked bis-(9-amino-1,2,3,4-tetrahydroacridine) (bis(7)-tacrine) is a
      potential palliative therapeutic agent for Alzheimer's disease (AD), on the basis
      of its superior acetylcholinesterase (AChE) inhibition and memory-enhancing
      potency relative to tacrine. In this study we report that bis(7)-tacrine exhibits
      a potentially complementary central nervous system action, antagonism of GABA(A)
      receptor function. Bis(7)-tacrine displaced [3H]muscimol from rat brain membranes
      with an apparent Ki of 6.0 microM; tacrine and physostigmine were shown to be 18
      and 170 times less potent, respectively. In whole-cell patch-clamp recordings,
      bis(7)-tacrine inhibited GABA-induced inward current with an IC50 of 5.6 microM,
      and shifted the GABA concentration-response curve to the right in a parallel
      manner. These results suggest that bis(7)-tacrine is a competitive antagonist of
      the GABA(A) receptor.

PMID- 10208551
TI  - Survival factors promote BDNF protein expression in mesencephalic dopaminergic
      neurons.
AB  - The aim of the present study was to characterize signals and/or molecules which
      regulate BDNF protein expression in mesencephalic dopaminergic neurons. Treatment
      of mesencephalic cells with dibutyryl-cAMP (dbcAMP), 30 mM K+ (HK+), or the
      antimitotic ara-C not only promoted the survival of tyrosine hydroxylase
      expressing (TH+) neurons but also increased the proportion of these cells that
      were immunopositive for BDNF. The effect of dbcAMP was mimicked by forskolin, a
      known adenylate cyclase activator. It was not antagonized by PKA inhibitors.
      Increases in BDNF expression resulting from K+-induced depolarization or ara-C
      treatment were abolished, respectively, by the L-type calcium channel blocker
      nifedipine and the deoxynucleotide dCTP. BDNF added exogenously to the cultures
      improved the survival of TH+ neurons. However, induction of the expression of
      BDNF in these neurons by dbcAMP, HK+ or ara-C was apparently not responsible for
      survival promotion by these factors.

PMID- 10208552
TI  - Plasticity in the motor system related to therapy-induced improvement of movement
      after stroke.
AB  - Neuroplasticity might play a beneficial role in the recovery of function after
      stroke but empirical evidence for this is lacking thus far. Constraint-induced
      (CI) therapy was used to increase the use of a paretic upper extremity in four
      hemiparetic stroke patients. Dipole modeling of steady-state movement-related
      cortical potentials was applied before and after training and 3 months later. The
      source locations associated with affected hand movement were unusual at follow-up
      because activation of the ipsilateral hemisphere was found in the absence of
      mirror movements of the unaffected hand. This long-term change may be considered
      as an initial demonstration of large-scale neuroplasticity associated with
      increased use of the paretic limb after application of CI therapy.

PMID- 10208553
TI  - Leupeptin protects sensory hair cells from acoustic trauma.
AB  - Calpains, a family of calcium activated proteases, promote the breakdown of
      cellular proteins, kinases, phosphatases and transcription factors. Calpain
      inhibitors attenuate some neurodegenerative processes in certain cell types. Here
      we show that leupeptin, a potent calpain inhibitor, protects the sensory hair
      cells in the inner ear from acoustic overstimulation (48 h, 100 or 105 dB SPL,
      octave band noise at 4 kHz). Acoustic overstimulation caused a significant
      increase in calpain immunolabeling in the sensory epithelium suggesting a
      possible role in noise-induced cochlear degeneration. Infusion of leupeptin into
      the inner ear significantly reduced the amount of sensory cell loss from acoustic
      overstimulation. However, leupeptin did not protect against hair cell loss from
      the ototoxic drug, carboplatin.

PMID- 10208554
TI  - Benzodiazepines do not modulate desensitization of recombinant alpha1beta2gamma2
      GABA(A) receptors.
AB  - Previous studies suggest that diazepam (DZP) increases the desensitization rate
      of GABA(A) receptors, although this effect could simply be a consequence of the
      DZP-induced increase in GABA sensitivity rather than a direct modulation of
      desensitization kinetics. To distinguish these two possibilities, voltage clamp
      recordings were performed on rat alpha1beta2gamma2 GABA(A) receptors expressed in
      Xenopus laevis oocytes. Complete GABA concentration-response relationships were
      obtained in the absence and presence of 1 microM DZP and the observed shift in
      GABA sensitivity (approximately 2.5-fold) was used to adjust GABA and GABA plus
      DZP to the same level of activation. In this case, DZP had no significant effect
      on either the rate of onset or recovery from desensitization. This suggests that
      the apparent effect of DZP on the rate of desensitization is secondary to the
      increase in GABA sensitivity and not due to a direct effect on the process of
      desensitization.

PMID- 10208555
TI  - Selective visual streaming in face recognition: evidence from developmental
      prosopagnosia.
AB  - Computational considerations suggest that efficient face identification requires
      the categorization and exclusive streaming of previously encoded face visual
      primitives into a dedicated face recognition system. Unique evidence supporting
      this claim is provided by a rare case of developmental pure prosopagnosia with
      otherwise normal visual and cognitive functions. Despite his normal visual memory
      and ability to describe faces, he is extremely impaired in face recognition. An
      early event related brain potential (N170) that is normally elicited exclusively
      by human faces, showed no specificity in this person. MRI revealed a smaller then
      normal right temporal lobe. These data emphasize the indispensability of the
      early streaming process for face recognition.

PMID- 10208556
TI  - Tracking the time course of object categorization using event-related potentials.
AB  - Object categorization processes were investigated by measuring event-related
      potentials while subjects categorized objects at the superordinate (e.g. animal),
      basic (e.g. dog) and subordinate (e.g. beagle) levels of abstraction. An enhanced
      negative deflection (N1) was found at posterior recording sites for subordinate
      level categorizations compared with basic level categorizations and was
      interpreted as a marker of increased visual analysis. In contrast, superordinate
      level categorizations produced a larger frontal negativity relative to basic
      level categorizations and were interpreted as an indicator of increased semantic
      processing. These results suggest a neurophysiological basis for the separate
      cognitive processes responsible for subordinate and superordinate object
      categorizations.

PMID- 10208557
TI  - Increased neuronal damage in apolipoprotein E-deficient mice following global
      ischaemia.
AB  - There is accumulating evidence that apolipoprotein E (apoE) plays a role in
      regulating the response to and outcome following brain injury. The present study
      compared the histological outcome and recovery following an episode of global
      ischaemia in apoE-deficient mice and wild-type littermates (12-week-old males, n
      = 8 per group). Transient global ischaemia was induced for a period of 17 min and
      the animals were allowed to recover for 72 h. Transient global ischaemia induced
      selective neuronal degeneration in several brain regions in wild-type mice. There
      was statistically significant increased ischaemic neuronal damage in apoE
      deficient mice compared with wild-type mice in six of the seven regions examined
      (hippocampal regions CA1, CA3/CA4 and dentate gyrus; thalamus; cortex and caudate
      nucleus; P < 0.05). The data substantiate a role for apoE in modifying the
      response of the CNS to acute injury.

PMID- 10208559
TI  - Modulation of morphine analgesia in alphaCGRP mutant mice.
AB  - A homozygous CGRP-/- mouse line was generated by the targeted disruption of exon
      5 in the calcitonin/alphaCGRP gene using homologous recombination. The mutant
      mice lack alphaCGRP mRNA. Furthermore CGRP immunoreactivity almost completely
      disappears from the spinal cord and is not at all observed in spinal ganglia and
      muscle synapses. However, motor end plates were still detected by
      acetylcholinesterase staining. Antinociceptive behavior tested by the tail flick
      and hot plate tests did not significantly differ in mutant and wild-type mice,
      except when challenged by morphine. Paradoxically, morphine analgesia was reduced
      in mutant mice compared with controls in the tail flick test, but not in the hot
      plate test. Thus, alphaCGRP differentially modulates opiate pain pathways.

PMID- 10208558
TI  - DNA pooling and dense marker maps: a systematic search for genes for cognitive
      ability.
AB  - Pooling DNA from subjects within a group and comparing the pooled DNA across
      groups for a dense map of DNA markers offers a solution to the conundrum that
      linkage is systematic but not powerful whereas allelic association is powerful
      but not systematic. We used DNA pooling to screen 66 markers on chromosome 22 in
      original and replication samples of children of high general cognitive ability
      (g) and controls of average g. Although none of these markers survived our three
      stage screening design (original pooling, replication pooling, individual
      genotyping), the results of DNA pooling were largely confirmed by individual
      genotyping. We can therefore exclude associations of major effect size on
      chromosome 22 for g, a key variable for cognitive neuroscience research on
      learning and memory.

PMID- 10208560
TI  - Cultured motor neurons possess calcium-permeable AMPA/kainate receptors.
AB  - We examined the biology of AMPA/kainate-induced motor neuron degeneration using
      dissociated spinal cord cultures and motor neuron-specific antibodies which
      enable characterization of individual motor neurons in culture. Cobalt, which is
      thought to pass through Ca2+-permeable AMPA/kainate receptors following kainate
      exposure, labeled motor neurons in spinal cord cultures. The analysis of AMPA
      subunit distribution in dissociated motor neurons revealed a unique pattern of
      glutamate receptor (GluR) subunits in those cells; the GluR1 subunit was found in
      all spinal cord neurons, but the GluR2 subunit was not found in identified
      dissociated motor neurons. These data suggest that selective sensitivity of motor
      neurons to non-NMDA receptor activation is due, at least in part, to the presence
      of Ca2+-permeable AMPA/kainate receptors.

PMID- 10208561
TI  - The selection and suppression of action: ERP correlates of executive control in
      humans.
AB  - A key aspect of higher cortical function is the ability to selectively withhold
      or suppress action where appropriate. To examine the time course of executive
      control we used dense-sensor EEG recording techniques to study event-related
      electrical potentials (ERPs) during a visual 'go/no-go' task. We show that during
      both go and no-go trials there is a positive deflection in the ERP, which
      develops over posterior parietal sensors approximately 350 ms (P300) after the
      onset of a conditional visual stimulus, but is selectively suppressed during no
      go trials. We also show that this modulation of the parietal P300 is preceded by
      a negative deflection in the ERP recorded over frontal cortex (N2), which is
      apparent only for no-go trials. We suggest that this signal provides an
      electrophysiological marker in man for the decision to withhold the execution of
      a motor response.

PMID- 10208562
TI  - Depletion of GDNF from primary afferents in adult rat dorsal horn following
      peripheral axotomy.
AB  - Glial cell line-derived neurotrophic factor (GDNF) is produced in a subset of
      adult rat spinal ganglion neurons and anterogradely transported to the
      superficial dorsal horn. In this study the effect of sciatic nerve axotomy on the
      expression of GDNF protein in the dorsal horn was investigated, using
      immunocytochemistry. Image analysis showed a 44% decrease relative to the non
      transected side after 5 days survival, progressing to more than 80% decrease
      after 10 days and remaining so for at least 100 days. This rapid and strong
      decrease suggests active down-regulation of GDNF protein after peripheral
      axotomy. The observed down-regulation of GDNF is compared with changes observed
      for other substances in primary afferents after peripheral axotomy and is
      discussed in light of its presumed trophic or transmitter role in nociception.

PMID- 10208563
TI  - Eye position encoding in the macaque ventral intraparietal area (VIP).
AB  - Many neurons in area VIP encode the location of visual stimuli in a non
      retinocentric frame of reference. In this context the question needed to be
      addressed whether the underlying coordinate transformation of the incoming visual
      signals could be generated within area VIP or whether this information would have
      to arrive from other areas. We tested 74 neurons in area VIP of two awake monkeys
      for an influence of eye position while animals performed a fixation task. More
      than half of the neurons (40/74) revealed an eye position effect. At the
      population level, however, this effect was balanced out. We suggest that local
      connections within area VIP could be used to generate an encoding of visual
      information in a non-retinocentric frame of reference.

PMID- 10208564
TI  - The -491AA polymorphism in the APOE gene is associated with increased plasma apoE
      levels in Alzheimer's disease.
AB  - Recent evidence suggests that a polymorphism in the regulatory region of the
      apolipoprotein E gene (APOE) is associated with an increased risk for developing
      Alzheimer's disease (AD) independent of that conveyed by the epsilon4 allele of
      APOE. Previous work by our group indicated that plasma apolipoprotein E (apoE)
      levels were elevated in AD, raising the possibility that the -491 genotype might
      modify AD risk by increasing expression of the APOE gene. In a total of 638
      individuals the -491AA genotype was significantly associated with AD (P < 0.005)
      while the TT genotype was associated with controls (P < 0.005). In 138
      individuals the AA genotype showed significantly higher plasma apoE levels,
      independent of epsilon4 and AD status (P < 0.01) as well as within control and AD
      groups (P < 0.05). Within the AD group the AA genotype showed increased apoE
      levels when compared to AA controls (P < 0.0001). These results suggest that the 
      491 AA genotype is associated with increased plasma apoE levels, providing a
      potential basis for elucidating how that genotype increases the risk for
      developing AD.

PMID- 10208565
TI  - First and second order maternal behavior related afferents of the lateral
      habenula.
AB  - We demonstrated previously that the lateral habenula (Lhb) mediates maternal
      behavior. Our present goal was to identify the first and second order afferent
      connections of the Lhb, particularly those relevant for maternal behavior. Using
      pseudorabies virus (PRV) as a retrograde transneuronal tracer and the retrograde
      tracer Fluoro-Gold, we identified first order Lhb afferent projections from the
      lateral preoptic area, bed nucleus of the stria terminalis, nucleus accumbens and
      ventral tegmental area, each important for the display of maternal behavior.
      Maternally relevant second order neurons originated from the medial preoptic area
      and amygdala. Additional regions with first and second order neurons afferent to
      the Lhb were also identified.

PMID- 10208566
TI  - NGF levels decrease in the spinal cord and dorsal root ganglion after spinal
      hemisection.
AB  - To examine changes in nerve growth factor (NGF) levels in spinal cord and dorsal
      root ganglia (DRG) after spinal injury, male Sprague-Dawley rats weighing 150-175
      g were given spinal hemisections. NGF content was measured at various post
      surgical times and compared with naive controls (n = 4 per time point) in the
      spinal cord, DRG and blood serum by ELISA techniques (Promega). Levels of NGF in
      the blood serum were significantly increased 8-fold at 48h but were significantly
      decreased in the spinal cord and DRG by 2- to 4-fold until 7 days postsurgery
      (ANOVA, p < 0.05). Contrary to accepted dogma, spinal injury results in decreased
      levels of NGF in the spinal cord and DRG following spinal injury.

PMID- 10208567
TI  - Neuropathological findings after intracerebral implantation of microdialysis
      catheters in sheep forebrain.

PMID- 10208568
TI  - Neuroanatomy, circuitry and plasticity of word reading.
AB  - The use of neuroimaging has provided a basis for suggesting the brain areas
      active during reading of words and sentences. When combined with high density
      electrical recording from the scalp, it is possible to obtain information on the
      time course of activation of these brain areas and compare them with the temporal
      structure of reading from studies of eye movements. The paper summarizes results
      in these areas and suggests how acquisition and practice of the skill might alter
      the circuitry involved.

PMID- 10208569
TI  - Presence of a voltage-dependent anion channel 1 in the rat postsynaptic density
      fraction.
AB  - Little is known about the molecular organization and functions of the
      postsynaptic density (PSD), a cytoskeletal specialization on the postsynaptic
      membrane. In an attempt to elucidate the protein composition of PSD, we have
      sequenced a 35 kDa protein of the rat forebrain PSD fraction. Amino acid sequence
      information of the tryptic peptides and immunoblot analyses revealed that the
      protein is a voltage-dependent anion channel 1 (VDAC1). VDAC1 was enriched in the
      PSD fraction and was partially soluble in 1% n-octyl glucoside (NOG) or Triton X
      100. Our data indicate that VDAC1, which is originally found in the outer
      mitochondrial membrane, is also present in the central nervous system (CNS)
      synapses in association with the PSD 'core'.

PMID- 10208570
TI  - N-methyl D-aspartate induced mechanical allodynia is blocked by nitric oxide
      synthase and cyclooxygenase-2 inhibitors.
AB  - The role of spinal NMDA receptors in mechanical nociceptive processing was
      assessed in sheep. Intrathecal NMDA (2 nmol-1 micromol) produced a significant
      reduction in mechanical withdrawal thresholds. This effect was attenuated by
      pretreatment with the NMDA receptor antagonist MK801 (100 nmol), the
      cyclooxygenase-2 (COX-2) inhibitor 5,5-dimethyl-3-(3-flourophenyl)-4-(4
      methylsulphonyl)phenyl-2(5H) furanone DFU; 200 nmol) and the nitric oxide
      synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME; 2 micromol),
      but not by the metabotropic glutamate receptor antagonist (S)-alpha-methyl-4
      carboxyphenylglycine (MCPG; 200 nmol-2 micromol) or the non-NMDA receptor
      antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX; 200 nmol-1 micromol). This
      first report of NMDA-induced mechanical allodynia suggests that spinal NMDA
      receptors are involved in mediating acute mechanical nociceptive processing
      through activation of NOS and COX-2 enzymes.

PMID- 10208571
TI  - The representation of pleasant touch in the brain and its relationship with taste
      and olfactory areas.
AB  - Although there has been much investigation of brain pathways involved in pain,
      little is known about the brain mechanisms involved in processing somatosensory
      stimuli which feel pleasant. Employing fMRI it was shown that pleasant touch to
      the hand with velvet produced stronger activation of the orbitofrontal cortex
      than affectively neutral touch of the hand with wood. In contrast, the
      affectively neutral but more intense touch produced more activation of the
      primary somatosensory cortex than the pleasant stimulus. This indicates that part
      of the orbitofrontal cortex is concerned with representing the positively
      affective aspects of somatosensory stimuli, and in further experiments it was
      shown that this orbitofrontal area is different from that activated by taste and
      smell. The finding that three different primary or unlearned types of reinforcer
      (touch, taste, and smell) are represented in the orbitofrontal cortex helps to
      provide a firm foundation for understanding the neural basis of emotions, which
      can be understood in terms of states elicited by stimuli which are rewarding or
      punishing.

PMID- 10208572
TI  - NR2B-containing NMDA receptors are up-regulated in temporal cortex in
      schizophrenia.
AB  - Saturation analyses of [3H]L-689,560, [3H]CGP 39653 and NMDA-specific
      [3H]ifenprodil binding revealed an equivalent increase (0.7 pmol/mg) in the
      number of [3H]L-689,560 and [3H]ifenprodil binding sites in superior temporal
      cortex (BA22) from drug-treated chronic schizophrenic patients and control
      subjects. No differences were observed between control and schizophrenic subjects
      for [3H]CGP 39653 binding in BA22, or for any of the radioligands binding to pre
      motor cortex (BA6). Since [3H]L-689,560, [3H]CGP 39653 and [3H]ifenprodil label
      the glycine, glutamate and ifenprodil sites of the NMDA receptor complex, which
      are associated with NR1, NR1/NR2A and NR1/NR2B subunits respectively, our
      findings suggest that NR2B-containing receptors are selectively up-regulated in
      superior temporal cortex in schizophrenia.

PMID- 10208573
TI  - Triggering action potentials in an axo-dendritic inhibitory synaptic terminal.
AB  - Intracellular activity of the slow adapting neurone (SAN) was recorded together
      with extracellular action potentials (APs) of SAN, fast adapting neurone and
      inhibitory fibre in the isolated stretch receptor of the moulting crayfish.
      Following strychnine application, spontaneous APs and seizure-like AP trains were
      observed. A delay of the inhibitory fibre APs relative to SAN inhibitory
      postsynaptic potential, their waveforms and their initiation by intracellular SAN
      hyperpolarization indicate that their generation was close to the inhibitory
      nerve terminal. Such antidromic (ectopic) APs assert their postsynaptic action on
      both receptor neurones via the axon reflex. The findings provide first evidence
      of antidromic APs generated in the vicinity of inhibitory terminals, their direct
      and axon reflex-mediated action on target neurones and support a hypothesis that
      increased terminal excitability contributes to seizure activity.

PMID- 10208574
TI  - Magnetic resonance imaging of the cochlea, spiral ganglia and eighth nerve of the
      guinea pig.
AB  - The membranous labyrinth of the guinea pig cochlea and retrocochlear neural
      structures were investigated by magnetic resonance imaging (MRI) using an
      experimental system with a field strength of 4.7T and a single turn surface coil
      25 mm in diameter, or standard resonators of 34 or 70 mm in diameter and gradient
      field strengths of 950 mTm and 200 mTm. High-resolution 2-D and 3-D images of 0.3
      1.0 mm slice thickness were acquired by a rapid acquisition with relaxation
      enhancement (RARE) sequence and a standard multi-echo technique. Structural and
      dimensional aspects of the cochlea were resolved in vitro and in vivo down to <50
      microm, showing the scala vestibule, scala media, scala tympani, spiral ganglia
      and the cochlear (eighth) nerve. In vivo perfusions with the gadodiamide (GdDTPA
      BMA) chelate-bound paramagnetic gadolinium ion resulted in dynamic temporal
      enhancement of the scala vestibule and scala tympani, but did not penetrate the
      scala media.

PMID- 10208575
TI  - Circadian modulation of the ryanodine receptor type 2 in the SCN of rodents.
AB  - We examined the temporal modulation of intracellular calcium release channels in
      the suprachiasmatic nucleus (SCN). We found a circadian rhythm in [3H]ryanodine
      binding that was specific to the SCN. The peak in the rhythm occurred at CT 7 and
      was due to an increase in Bmax, which correlated well with immunoblots showing an
      increase in RyR-2 expression in the SCN. Double immunohistochemical studies
      showed that RyR-2 was expressed exclusively in neurons. Ryanodine and caffeine
      applied around CT 7-9 advanced the clock phase in a hamster brain slice
      preparation. No rhythm of IP3R was seen in any of the brain areas studied. Our
      results indicate that RyR-2 exhibits an endogenous rhythm, which influences the
      intracellular calcium dynamics and thus modulates SCN activity.

PMID- 10208576
TI  - A new GTP-cyclohydrolase I mutation in an unusual dopa-responsive dystonia,
      familial form.
AB  - We found a new mutation in the GTP cyclohydrolase gene involved in dopa
      responsive dystonia. We sequenced the GTP cyclohydrolase gene in a family with
      four siblings affected by this disorder and identified an A-T mutation in exon 2,
      leading to a non conservative amino acid substitution at codon 135 of the protein
      (Ile135Lys), which may change the conformation of the binding site of this
      enzyme. The clinical evolution was heterogeneous among carriers of the same
      mutation, underlining the involvement of other determinants modulating the
      occurrence of the disease such as genetic or environmental susceptibility
      factors.

PMID- 10208577
TI  - Serotonergic agonists behave as partial agonists at the dopamine D2 receptor.
AB  - RAT dopamine D2short receptors expressed in CHO cells were characterized by
      activation of [35S]GTPgammaS binding. There were no significant differences
      between the maximal effects seen in activation of [35S]GTPgammaS binding caused
      by dopaminergic agonists, but the effects of 5-HT, 8OH-DPAT and 5
      methoxytryptamine amounted to 47 +/- 7%, 43 +/- 5% and 70 +/- 7% of the dopamine
      effect, respectively. The dopaminergic antagonist (+)butaclamol inhibited
      activations of both types of ligands with equal potency (pA2 = 8.9 +/- 0.1),
      indicating that only one type of receptor is involved. In competition with
      [3H]raclopride binding, dopaminergic agonists showed 53 +/- 2% of the binding
      sites in the GTP-dependent high-affinity state, whereas 5-HT showed only 20 +/-
      3%. Taken together, the results indicate that serotonergic agonists behave as
      typical partial agonists for D2 receptors with potential antiparkinsonian
      activity.

PMID- 10208578
TI  - A distinct familial presenile dementia with a novel missense mutation in the tau
      gene.
AB  - We report a Japanese family with early onset hereditary frontotemporal dementia
      and a novel missense mutation (Ser305Asn) in the tau gene. The patients presented
      with personality changes followed by impaired cognition and memory as well as
      disorientation, but minimal Parkinsonism. Imaging studies showed fronto-temporal
      atrophy with ventricular dilatation more on the left, and postmortem examination
      of the brain revealed numerous neurofibrillary tangles (NFTs) with an unusual
      morphology and distribution. Silver-stained sections showed ring-shaped NFTs
      partially surrounding the nucleus that were most prominent in frontal, temporal,
      insular and postcentral cortices, as well as in dentate gyrus. Cortical NFTs were
      restricted primarily to layer II, and were composed of straight tubules. Numerous
      glial cells containing coiled bodies and abundant neuropil threads were detected
      in cerebral white matter, hippocampus, basal ganglia, diencephalon and brain
      stem, but no senile plaques or other diagnostic lesions were seen. Both the glial
      and neuronal tangles were stained by antibodies to phosphorylation-independent
      and phosphorylation-dependent epitopes in tau. Thus, this novel mutation causes a
      distinct familial tauopathy.

PMID- 10208579
TI  - Early-onset Alzheimer's disease caused by a novel mutation at codon 219 of the
      presenilin-1 gene.
AB  - Mutations in the presenilin 1 (PS1) gene are responsible for approximately 50% of
      early onset autosomal-dominant Alzheimer's disease cases. A PCR based mutation
      detection method, chemical cleavage of mismatch, was used to detect a novel PS1
      mutation in the coding sequence of the PS1 gene. Sequencing confirmed a T to C
      transition altering a leucine to proline at codon 219 of the PS1 gene. This is a
      novel mutation in exon 7 of the PS1 gene occurring outside the transmembrane
      regions of IV and V.

PMID- 10208580
TI  - Effects of bFGF and TGFbeta on the expression of amyloid precursor and B-cell
      lymphoma protooncogene proteins in the rat retina.
AB  - The pattern of immunoreactivity for amyloid precursor (APP) and B-cell lymphoma
      protooncogene (Bcl-2) proteins in the rat retina was studied after intravitreal
      injection of basic fibroblast growth factor (bFGF) or transforming growth factor
      beta (TGFbeta). In normal control retinas, intense immunostaining of APP and Bcl
      2 was observed primarily in the endfeet and proximal part of radial processes of
      Muller glial cells. A dose-dependent reduction in immunostaining of APP and Bcl-2
      in Muller cells was observed after injection of bFGF and TGFbeta. These results
      provide the first evidence that APP and Bcl-2 can be down-regulated by cytokines
      in vivo.

PMID- 10208581
TI  - Decreased neuropeptide content in the spinal cord of aged rats: the effect of GM1
      ganglioside.
AB  - This study investigated the status of substance P (SP), methionine-enkephalin
      (Met-Enk) and dynorphin A(1-13) (Dyn A) in the spinal cord of aged Sprague-Dawley
      rats and the effect of GM1 ganglioside on these neuropeptides. SP and Met-Enk,
      but not Dyn A, were decreased in both dorsal and ventral horns of the aged spinal
      cord. Treatment with GM1 ganglioside (30 mg/kg i.p., daily for 30 days) restored,
      in part, the neuropeptide deficits in the ventral horns, but not in the dorsal
      horns. This information might be important for understanding the sensory and
      motor deficits associated with ageing, and how the spinal cord neuropeptides
      might be amplified in the aged spinal cord.

PMID- 10208582
TI  - A new place conditioning paradigm to study tolerance to opiates in mice.
AB  - Tolerance to the rewarding properties of morphine was investigated in mice using
      a new conditioned place preference (CPP) procedure. Four pairings of morphine
      with specific environmental cues induced a significant CPP for the drug-paired
      cues. Further opiate conditioning trials in the presence of the same
      environmental cues revealed no change in the drug-induced CPP on repeated test
      sessions. Subsequent exposure of the same animals to conditioning trials by
      pairing morphine with a set of novel environmental cues showed that the opiate
      was still able to produce a CPP in mice treated with a total of 16 morphine
      injections. The present CPP paradigm may prove useful to investigate tolerance to
      the rewarding properties of drugs of abuse.

PMID- 10208583
TI  - Stressor-induced alterations in serotonergic activity in an animal model of
      depression.
AB  - The present study examined the effect of two neurogenic stressors (air puff and
      restraint) and a metabolic stressor (lipopolysaccharide; LPS 100 microg/kg, i.p.)
      on accumbal serotonergic neurotransmission in the olfactory bulbectomized (OB)
      rat model of depression. Both air puff and restraint stress caused greater
      increases in accumbal 5-HIAA in OB than in sham-operated rats. In contrast,
      bulbectomy resulted in a blunted serotonergic response to a challenge with LPS (a
      metabolic stressor). In addition, OB rats displayed significantly lower basal
      levels of 5-HIAA than sham-operated counterparts, a finding consistent with
      previous reports of the OB rat being a model of hyposerotonergic depression. The
      relevance of these findings to stressor-provoked depressive-like behaviors in the
      OB rat are discussed.

PMID- 10208584
TI  - Increased intracellular calpain detection in experimental focal cerebral
      ischemia.
AB  - Calpains are intracellular proteinases whose proteolytic activity is directed
      mainly against the cytoskeleton and regulatory proteins. We studied the presence
      of calpain by immunohistochemistry in a rat model of reversible focal cerebral
      ischemia (3 h) at various times of reperfusion. The numbers of calpain-positive
      cells on the ischemic side were compared with the non-ischemic side. In controls
      only 2 +/- 1% cells were positive, whereas the cortex of the ischemic vs the non
      ischemic side showed 88 +/- 3% vs 13 +/- 4% calpain-positive cells (p < 0.001),
      and the basal ganglia 47 +/- 3% vs 13 +/- 4% (p < 0.01) after 3 h ischemia and 24
      h reperfusion. This is the first demonstration of elevated intracellular levels
      of calpains in areas of cerebral ischemia. Longer reperfusion resulted in an
      increase in calpain positivity.

PMID- 10208585
TI  - X-irradiation-induced loss of O-2A progenitor cells in rat spinal cord is
      inhibited by implants of cells engineered to secrete glial growth factor 2.
AB  - The loss of O-2A progenitor cells has been implicated as a critical event in
      radiation-induced spinal cord demyelination. To investigate whether glial growth
      factor 2 (GGF2) affects the number of O-2A cells in the irradiated rat cervical
      spinal cord, an ex vivo gene therapy approach was applied in which CHO cells
      engineered to express recombinant human GGF2 were injected into the cisterna
      magna of adult rats. Spinal cord irradiation reduced the number of O-2A cells in
      a dose-dependent manner. However, this radiation-induced decrease in O-2A
      progenitor cells was significantly attenuated by the delivery of GGF2 after
      irradiation. These data indicate that the cell-mediated delivery of GGF2 can
      reduce the loss of O-2A progenitors after irradiation.

PMID- 10208586
TI  - Limbic seizures increase pronociceptin mRNA levels in the thalamic reticular
      nucleus.
AB  - We studied pronociceptin gene expression following limbic seizures. Northern blot
      analysis revealed increased pronociceptin mRNA levels in the thalamus (but not in
      the hippocampus) 3-24 h after kainate administration, with maximal effect (2-fold
      increase over basal levels) reached at 6 h. No variation in pronociceptin mRNA
      levels was observed 1-6 h after a stimulus-evoked kindled seizure. Carrageenan
      failed to affect pronociceptin gene expression in the thalamus, indicating that
      pain and/or acute stress do not account for kainate effects. In situ
      hybridization revealed that kainate evokes a dramatic (4-fold) increase in
      pronociceptin mRNA levels over the thalamic reticular nucleus. Kindled seizures
      evoked only a small, non-significant increase in pronociceptin gene expression
      over the dentate gyrus of the hippocampus.

PMID- 10208587
TI  - 5-HT4 receptor modulation of acetylcholine outflow in guinea pig brain slices.
AB  - The effect of the 5-HT4 agonist, BIMU-8 was studied on [3H]choline outflow in
      guinea pig brain slices and synaptosomes. BIMU-8 did not modify [3H]choline
      efflux in slices kept at rest, but increased [3H]choline outflow in electrically
      stimulated slices of cerebral cortex (CC), hippocampus (hip) and nucleus basalis
      magnocellularis (nbm). This effect was prevented by the selective 5-HT4
      antagonist, GR 125487. Conversely, BIMU-8 did not affect [3H]choline efflux in
      hippocampal synaptosomes depolarized with KCl 20 mM. These results provide
      evidence that BIMU-8 increases the electrically triggered [3H]choline efflux in
      CC, hip and nbm slices. A possible role of 5-HT4 agonists in memory and learning
      diseases is suggested.

PMID- 10208588
TI  - Effects of acute and chronic fluoxetine treatment of CRH-induced anxiety.
AB  - The effects of acute and chronic fluoxetine treatment on anxiogenic effect of
      corticotropin-releasing hormone (CRH) were studied in the social interaction test
      in male Sprague-Dawley rats. Injection of CRH (100 ng, i.c.v.), fluoxetine (5
      mg/kg, i.p.) or their combination had significant anxiogenic effects (decrease in
      total interaction time and increase in self-grooming) in the social interaction
      test. The effects of CRH and fluoxetine in combination were not additive.
      Fluoxetine, but not CRH significantly inhibited locomotor activity. After chronic
      fluoxetine treatment (5 mg/kg/day, 21 days) the acute anxiogenic effects of
      either CRH or fluoxetine were abolished. Our studies provide evidence for a 5
      HT/CRH interaction in the regulation of anxiety.

PMID- 10208589
TI  - Reduced expression of brain-derived neurotrophic factor protein in Parkinson's
      disease substantia nigra.
AB  - Several in vitro and in vivo studies have shown that brain-derived neurotrophic
      factor (BDNF) promotes survival of damaged mesencephalic dopaminergic neurons.
      Using a specific antibody directed against human recombinant BDNF, we studied the
      expression of the protein at the cellular level in the post-mortem mesencephalon
      of control subjects and patients with Parkinson's disease (PD). In control
      subjects, BDNF was expressed in all mesencephalic regions containing dopaminergic
      neurons, and in the substantia nigra pars compacta (SNpc) 65% of the melanized
      neurons expressed BDNF. In the PD SNpc, the total number of pigmented neurons
      containing BDNF was reduced to 9.6% of the corresponding control value. In
      contrast, the number of pigmented neurons non-immunoreactive for BDNF was reduced
      to 23.9% of the corresponding control value. This result appears to indicate that
      SNpc melanized neurons not expressing BDNF have a 2.5-fold greater probability of
      surviving than BDNF-positive melanized neurons. Furthermore, we found that in
      parkinsonian mesencephalon almost all dopaminergic neurons containing Lewy bodies
      were immunoreactive for BDNF. These findings demonstrate a reduced expression of
      BDNF in PD and suggest that BDNF protein expression does not protect melanized
      SNpc neurons from the degenerative process in this disease.

PMID- 10208590
TI  - Isolation of human delta-catenin and its binding specificity with presenilin 1.
AB  - We screened proteins for interaction with presenilin (PS) 1, and cloned the full
      length cDNA of human delta-catenin, which encoded 1225 amino acids. Yeast two
      hybrid assay, GST binding assay and immunoprecipitation demonstrated that delta
      catenin interacted with a hydrophilic loop region in the endoproteolytic C
      terminal fragment of PS1, but not with that of PS-2. These results suggest that
      PS1 and PS2 partly differ in function. PS1 loop fragment containing the
      pathogenic mutation retained the binding ability. We also found another armadillo
      protein, p0071, interacted with PS1.

PMID- 10208591
TI  - Expression of mRNA encoding alpha1E and alpha1G subunit in the brain of a rat
      model of absence epilepsy.
AB  - Low voltage-activated calcium channels are thought to play a key role in the
      generation of spike and waves discharges characteristic of absence epilepsy.
      Therefore, the expression level of mRNA encoding calcium channel alpha1E and
      alpha1G subunits was measured in the brain of genetic absence epilepsy rats from
      Strasbourg (GAERS). Using quantitative RT-PCR and in situ hybridization, no
      difference was found in alpha1G mRNA expression between GAERS and control
      animals, while a decreased expression of alpha1E was seen in the cerebellum and
      the brain stem of the GAERS. This phenomenon was not observed in young animals
      when the epileptic phenotype is not expressed.

PMID- 10208592
TI  - Histamine and tumor necrosis factor-alpha production from purified rat brain mast
      cells mediated by substance P.
AB  - The effect of cytokines and neuropeptides on neuroimmune functions has not been
      completely elucidated and recent evidence suggests an important role for these
      molecules linking the neuroimmune system and inflammatory events. The aim of this
      study was to analyse the effect of substance P (SP) on a pure population of
      hypothalamic brain mast cell (BMC). A pure population of BMC challenged with 10(
      8) M SP gave 78% histamine release (HR) and secreted 600 pg/ml of tumor necrosis
      factor-alpha (TNF-alpha) as determined by ELISA. The production of TNF-alpha
      mRNA, measured by a competitive RT-PCR, was 14 times higher than that in
      unstimulated cells. The secretion of histamine and TNF-alpha from BMC after
      stimulation with SP supports the hypothesis that these mediators could induce an
      initial response in neuroinflammatory diseases.

PMID- 10208593
TI  - Rapid cortical motor output map changes assessed by the triple stimulation
      technique.
AB  - The amplitudes of motor evoked potentials (MEPs) were mapped by transcranial
      magnetic stimulation (TMS) using the triple stimulation technique (TST) in 11
      normal individuals. Stimuli were given while the subjects were (a) distracted,
      (b) concentrating on their target (recorded) hand, and (c) concentrating on their
      contralateral hand. Within seconds, the proportion of excited motor units
      increased, similarly in all subjects, by an average of 70% from (a) to (b), and
      by 48% from (a) to (c). At the optimal stimulation site, results obtained with
      the TST were compared to those of conventional MEPs. The TST proved superior in
      detecting the rapid changes of the motor output caused by the non-specific mental
      tasks studied.

PMID- 10208594
TI  - c-Fos basal immunoreactivity decreases in rat spinal cord during normal ageing.
AB  - The pattern of distribution in rat spinal cord and changing pattern during normal
      ageing of c-Fos expression were investigated by immunohistochemical staining in
      male Sprague-Dawley rats at the age of 1 week, 5 months and 2 years. c-Fos
      immunoreactivity was observed diffusely in gray matters in neonatal rats,
      preferentially located in deep dorsal horn and around central canal. Compared
      with those of neonatal rats, these cells decreased prominently in adult rats. In
      aged rats, immunoreactive cells were not seen in any segments. c-Fos
      immunoreactivity in spinal cord may be related to stress response, functional
      differentiation, and in part, neuronal death with target dependence. In
      conclusion, we demonstrated for the first time that c-Fos expression patterns
      change during normal ageing.

PMID- 10208595
TI  - Repetitive transcranial magnetic stimulation has a beneficial effect on
      bradykinesia in Parkinson's disease.
AB  - The effect of focal 5 Hz repetitive transcranial magnetic stimulation (rTMS) of
      the motor hand area (M1) on bradykinesia was studied in 12 unmedicated patients
      with Parkinson's disease (PD). On 2 separate days, a real-rTMS was applied to M1
      contralaterally to the more severely affected limb or a frontal sham-rTMS was
      applied 3 cm anteriorly to Fz in a random order. Stimulus intensity was 10% below
      resting motor threshold. Before and 20 min after rTMS, patients performed 15
      consecutive pointing movements with the index finger contralaterally to the
      stimulated M1. Compared with sham-rTMS, real-rTMS over the contralateral M1
      caused a significant decrease in total movement time without affecting end-point
      accuracy. Our data provide evidence that 5 Hz rTMS over M1 can improve
      bradykinesia in PD patients beyond the time of magnetic stimulation.

PMID- 10208596
TI  - Ethanol inhibits G-protein-mediated glucose uptake by C6 glioma cells.
AB  - The mechanism of ethanol inhibition of glucose uptake was investigated using C6
      glioma cells. Basal [3H]2-deoxy-D-glucose (2DG) uptake by C6 cells was inhibited
      by ethanol in a concentration-dependent manner. Fifty, 75 and 100 mM ethanol
      significantly inhibited basal 2DG uptake by 12, 20 and 23%, respectively (p <
      0.05). Carbachol (an agonist acting via G protein-coupled receptors) stimulated
      the uptake by 26% (p < 0.05). In the presence of 100 mM ethanol, the ability of
      carbachol to stimulate 2DG uptake was abolished. In contrast, ethanol did not
      inhibit the ability of insulin to stimulate 2DG uptake. These results suggest
      that ethanol inhibits 2DG uptake by selectively interfering with G protein
      mediated signal transduction pathway.

PMID- 10208597
TI  - Position-dependent expression of inwardly rectifying K+ currents by hair cells of
      frog semicircular canals.
AB  - The identity and the expression of inwardly rectifying ionic currents were
      studied using the whole-cell variant of the patch-clamp technique in frog
      semicircular canal hair cells in situ. The currents were examined in club-,
      cylindrical- and pear-shaped sensory cells located in three discrete regions of
      the crista. A unique current of I(K1) type was distinguished based on its K+
      selectivity, rapid monoexponential activation, dependence of activation on
      external K+ and blockade by Ba2+ and Cs+. I(K1) was found in virtually all
      cylindrical hair cells of the central region and in club-shaped cells located in
      the halves of the peripheral regions closest to the centre of the crista. Pear
      shaped cells of the intermediate regions showed no inward rectification. The
      I(K1) density (pA/pF) varied along the crista depending on cell position, being
      maximal in cells located in the middle of the central region and decreased
      towards its ends. In the peripheral regions, the gradient of I(K1) increased
      towards the centre of the crista. Current clamp experiments showed that sensory
      cells having larger I(K1) constantly exhibited more negative resting potentials
      and required more depolarizing current to elicit an active response than cells
      having small or no I(K1).

PMID- 10208598
TI  - Normal planum temporale asymmetry in dyslexics with a magnocellular pathway
      deficit.
AB  - Developmental dyslexia has been associated with both abnormal hemispheric
      symmetry of the planum temporale (PT) and a deficit in the magnocellular visual
      pathway. We examined the relationship between these two abnormalities. Using
      sagittal magnetic resonance images and three methods, we measured the PT in
      dyslexic subjects with a documented magnocellular deficit and controls. Dyslexic
      subjects did not deviate from normal leftward PT asymmetry, but both groups
      became less left-lateralized with methods that excluded sulcul tissue. Results
      suggest that dyslexic subjects with a magnocellular deficit do not always have
      abnormal symmetry of the PT. PT symmetry may instead be related to a different
      subtype of dyslexia. In addition, PT asymmetry in any subject group depends on
      the measurement method.

PMID- 10208599
TI  - Photic induction of Period gene expression is reduced in Clock mutant mice.
AB  - The Clock mutation leads to abnormal circadian behavior and defective
      transcriptional activity of CLOCK, a basic helix-loop-helix (bHLH)/PAS protein.
      In situ hybridization was used to assess whether the Clock mutation affects the
      photic induction of mPer1, mPer2, and c-fos in the mouse suprachiasmatic nucleus
      (SCN). Exposure of wild-type mice to a 15 min light pulse at night rapidly
      induced expression of c-fos mRNA, with mPer1 and mPer2 mRNAs peaking later. Light
      exposure also increased c-fos, mPer1 and mPer2 mRNA levels in the SCN of
      homozygous Clock mutant mice, but the amplitude of the response to light was
      significantly reduced. Clock appears to play a role in circadian photoreception
      that is distinct from its role in the circadian oscillatory mechanism.

PMID- 10208600
TI  - Opioid receptors in the human cerebellum: evidence from [11C]diprenorphine PET,
      mRNA expression and autoradiography.
AB  - Little is known regarding opioid receptors in the human cerebellum. The present
      [11C]diprenorphine PET study investigated opioid receptor binding in the human
      cerebellum in vivo, and showed a differential binding level in cerebellar cortex,
      vermis and dentate nuclei. The additional study in vitro of opioid receptors in
      human cerebellar cortex and rat brain corroborated the presence of opioidergic
      mechanisms in the human cerebellum in contrast to the rat. A differential
      cellular distribution pattern was detected for the three major opioid receptors
      investigated. For the mu-receptor, and at a lower level for the kappa-receptor,
      mRNA expression was mainly observed over granule cells. Binding sites were most
      prominent in the molecular layer. For the delta-receptor no signal was detected.
      The consideration of cerebellar opioidergic mechanisms and the distribution
      patterns of the various opioid receptors may promote the understanding of
      cerebellar function and of opioidergic pharmacology in the human.

PMID- 10208601
TI  - Retrosplenial cortex inactivation selectively impairs navigation in darkness.
AB  - There is an emerging consensus that retrosplenial and posterior parietal cortex
      importantly contribute to navigation. Several theories of navigation have argued
      that these cortical areas, particularly retrosplenial cortex, are involved in
      path integration. In an effort to characterize the role of retrosplenial cortex
      in active navigation, the effects of temporary inactivation of retrosplenial
      cortex on spatial memory performance were evaluated in light and dark testing
      conditions. Inactivation of retrosplenial cortex selectively resulted in
      behavioral impairments when animals were tested in darkness. These data support
      the hypothesis that retrosplenial cortex contributes to navigation in darkness,
      perhaps by providing mnemonic associations of the visual and nonvisual
      environment that can be used to correct for cumulative errors that occur during
      path integration.

PMID- 10208602
TI  - Role of serotonergic neurons in L-DOPA-derived extracellular dopamine in the
      striatum of 6-OHDA-lesioned rats.
AB  - The effect of L-dihydroxyphenylalanine (L-DOPA) on extracellular dopamine (DA) in
      the striatum was determined by microdialysis in 6-hydroxydopamine (6-OHDA)
      lesioned rats treated with and without the serotonergic neurotoxin 5,7
      dihydroxytryptamine (5,7-DHT). At the same time the intensity of L-DOPA-induced
      rotational behavior was assessed. In 6-OHDA-lesioned rats treated with 5,7-DHT, L
      DOPA (50 mg/kg, i.p.) increased extracellular DA only to 20% of that measured in
      animals not treated with 5,7-DHT. Likewise, 6-OHDA-lesioned rats treated with 5,7
      DHT exhibited a significantly lower number of L-DOPA-induced rotations. These
      results suggest that serotonergic terminals in the striatum can convert
      exogenously administered L-DOPA into DA that can be released into the
      extracellular space.

PMID- 10208603
TI  - Transgenic mice expressing a dominant negative mutant interleukin-1beta
      converting enzyme show resistance to MPTP neurotoxicity.
AB  - Increasing evidence implicates apoptosis as a major mechanism of cell death in
      neurodegenerative diseases. Recent evidence has demonstrated that chronic
      administration of MPTP can lead to apoptotic cell death. In the present study we
      examined whether transgenic mice expressing a dominant negative inhibitor of
      interleukin-1beta convertase enzyme (ICE) are resistant to MPTP induced
      neurotoxicity. MPTP resulted in a significant depletion of dopamine, DOPAC and
      HVA in littermate control mice which were completely inhibited in the mutant
      interleukin-1beta converting enzyme mice. There was also significant protection
      against MPTP-induced depletion of tyrosine hydroxylase-immunoreactive neurons.
      There was no alteration in MPTP uptake or metabolism. These results provide
      further evidence that apoptotic cell death as well as ICE may play an important
      role in the neurotoxicity of MPTP.

PMID- 10208604
TI  - Calcium-dependent alterations in dendritic architecture of hippocampal pyramidal
      neurons.
AB  - Dendritic arbor formation and the underlying mechanisms are crucial for the
      functional connectivity and plasticity of neurons. We used a focal electric field
      to locally raise calcium levels in individual dendritic shafts of isolated
      hippocampal pyramidal neurons, in order to develop an accessible system for
      studying dendritic branch formation, and to test the role of calcium as an
      intrinsic signal that may participate in arborization. Filopodia were induced in
      a manner temporally and spatially related to induced calcium rises. Certain
      filopodia also thickened and were transformed into dendritic branches. These
      results suggest that calcium-mediated signaling can induce branching in
      dendrites, and describe an accessible system for studying the intracellular
      machinery that drives dendritic arborization.

PMID- 10208605
TI  - Zinc alleviates thermal hyperalgesia due to partial nerve injury.
AB  - Zinc has recently been shown to alleviate inflammatory hyperalgesia. In the
      present study, we showed that intrathecal, intraplantar or systemic injection of
      zinc chloride significantly relieved thermal hyperalgesia in rats with sciatic
      nerve injury. Alleviation of thermal hyperalgesia was dose dependent in each
      case, although higher doses were required for i.p. injections (ED50 = 13.6 nmol)
      than for intrathecal (ED50 = 0.05 nmol) or intraplantar injections (ED = 0.3
      nmol). Neither intrathecal nor intraplantar zinc chloride influenced thermal
      nociception in normal rats without nerve injury. The results provide the first
      evidence that zinc alleviates neuropathic hyperalgesia.

PMID- 10208606
TI  - Divalent cation selectivity of the subtypes of low voltage-activated Ca2+
      channels in thalamic neurons.
AB  - LVA Ca2+ current in isolated associative neurons from the laterodorsal thalamic
      nucleus of 14- to 17-day-old rats was dissected into two, 'fast' and 'slow',
      components based on the difference in the kinetics of inactivation. The
      selectivity of the channel responsible for the fast LVA current for Ca2+, Sr2+
      and Ba2+ (I(Ca):I(Sr):I(Ba) = 1.0:1.23:0.94) as well as the shifts of the I-V
      produced by these ions were found to be almost identical to those observed for
      LVA channels in other preparations. The channel responsible for the slow LVA
      current showed selectivity more characteristic of HVA Ca2+ channels
      (I(Ca):I(Sr):I(Ba) = 1.0:2.5:3.4), although the ability of Ca2+, Sr2+ and Ba2+ to
      shift its voltage dependence remained the same as for the fast channel.

PMID- 10208607
TI  - Spontaneous activity in the perinatal trigeminal nucleus of the rat.
AB  - The role of electrical activity in establishing appropriate connections in the
      trigeminal pathway remains controversial. We report here a novel observation of
      spontaneous activity in the perinatal trigeminal sensory nucleus between
      embryonic day (E) 16 to postnatal day (P) 8. Most of these spontaneous bursts had
      the same polarity and were of comparable amplitude to the trigeminal nerve-evoked
      response. This synchronized activity was abolished by bicuculline or kynurenic
      acid. Recording from the teased trigeminal root during the spontaneous bursts
      also showed a corresponding afferent depolarization. We speculate that the
      GABAergic depolarization of pre- and postsynaptic cells may contribute to the
      generation of the spontaneous activity and its propagation throughout the
      trigeminal sensory pathway, even in the absence of activity initiated from
      peripheral sensory receptors.

PMID- 10208608
TI  - Atrophie blanche.

PMID- 10208609
TI  - House dust mites in atopic dermatitis.

PMID- 10208610
TI  - Recent achievements in dermatologic research as a challenge and prologue for the
      future.

PMID- 10208611
TI  - Building ideas for tomorrow.

PMID- 10208613
TI  - Nurse's cap alopecia.
AB  - BACKGROUND: Traction alopecia associated with the nurse's cap is a relatively
      common form of occupational hair loss. METHODS: We examined 199 healthy South
      Korean nurses to assess the clinical and pathologic characteristics of traction
      alopecia caused by prolonged traction exerted at the point of attachment of the
      nurse's cap. RESULTS: Seven nurses (3.5% of 199) had hair loss at the pin site
      used to secure the nurse's cap. The lesions were exclusively localized on the
      parieto-occipital scalp. Histopathologic findings revealed characteristic
      cicatricial changes which showed a marked decrease in the number of hair
      follicles without inflammation. CONCLUSIONS: Nurse's cap alopecia is not an
      uncommon occupational alopecia, and appears to be a distinct clinical entity
      which should be distinguished from other forms of patchy alopecia.

PMID- 10208612
TI  - Allergic contact dermatitis in the United Arab Emirates.
AB  - BACKGROUND: No data exist on allergic contact dermatitis (ACD) in the United Arab
      Emirates (UAE). AIM: Our aim was threefold: (i) to determine the incidence of
      ACD; (ii) to identify responsible allergens using the European Standard Series,
      TRUE TEST, and other substances; (iii) to tentatively explore population-specific
      reactions in Al Ain, UAE. DESIGN: This is a prospective, descriptive, hospital
      based, study. SETTING: Tawam Hospital, Al Ain Medical District, UAE. PATIENTS:
      During the years 1989-1996, 373 patients (male: female = 2 : 3), presenting with
      cutaneous manifestations possibly related to contact allergy, were patch tested.
      RESULTS: 93.8% of patients presented with dermatitis affecting mostly the hands
      (45.1%), feet (21.4%), face (12.6%), and legs (4.6%). Two hundred and twenty-four
      patients (60%) (male : female = 1 : 2) tested positive for at least one
      substance. Nickel was the commonest sensitizer (15%) in both genders. "Fragrance
      mix" (8%), p-tertiary butylphenolformaldehyde (p-TBPF) resin (7.5%), thiomersal
      (7.5%), chromium (7.2%), cobalt (6.4%), ethylenediamine (6.4%), neomycin (5.1%),
      and parabens (5.1%) were prominent allergens. Glutardialdehyde, an additional
      substance tested together with the European Standard Series, scored significantly
      (4.8%). Variations from the results reported from other countries may be
      explained by the specific lifestyles and customs of the UAE population.
      CONCLUSIONS: Substances contained in the TRUE TEST, plus glutardialdehyde, may be
      considered as the standard series for patch testing in the UAE population.

PMID- 10208614
TI  - Skin problems of musicians.
AB  - OBJECTIVE: We investigated the skin problems of high level musicians in a
      professional orchestra. This study was prompted by our observation of violinists
      with skin changes. METHODS: Ninety-seven musicians were evaluated. Twelve
      reporting dermatitis associated with the playing of their instruments were patch
      tested. We also examined 20 singers (nonplayers). RESULTS: Positive patch test
      reactions to nickel and colophony were found in only three patients. Musicians
      were subject to a variety of skin problems from playing their instruments,
      however, such as hyperhidrosis, cheilitis, and calluses of the fingertips.
      Singers had skin problems including lichen planus, psoriasis, seborrheic
      dermatitis, and urticaria. It was thought that emotional factors exacerbate their
      problems. CONCLUSIONS: The results of this survey suggest a significant incidence
      of occupational- and stress-related skin problems in musicians.

PMID- 10208616
TI  - Propionibacterium acnes: interaction with complement and development of an enzyme
      linked immunoassay for the detection of antibody.
AB  - OBJECTIVE: To characterize the immune response to Propionibacterium acnes in acne
      patients. DESIGN: Comparison of serologic responses in acne and normal patients
      using counterimmunoelectrophoresis for antibody and an enzyme-linked
      immunosorbent assay (ELISA) to detect immunoglobulin G (IgG) antibody. SETTING:
      The serum of acne and nonacne patients from the Dermatology Clinic at the Medical
      College of Ohio was utilized for analysis. RESULTS: Using
      counterimmunoelectrophoresis, antibody was detected in 13 of 20 acne patients.
      The antigen was detectable as an anion in the barbital buffer at pH 8.2, strongly
      suggesting a carbohydrate component. By ELISA, the antibody proved to be IgG, and
      the bacteria and its water-soluble fractions were capable of fixing complement.
      CONCLUSIONS: The primary instigator of inflammation in acne vulgaris is an
      immunologic reaction to extracellular products of P. acnes. The immunologic
      response involves both humoral and cell-mediated pathways. The antibodies to P.
      acnes have not been characterized fully, although they are largely of the IgG
      class. We have further characterized the dominant antigen to have a carbohydrate
      component.

PMID- 10208615
TI  - Acneiform eruptions after facial beauty treatment.
AB  - BACKGROUND: Female patients in the post-adolescent age group presented with
      predominantly deep-seated nodules and a few comedones situated mainly on the
      cheeks. As most of these subjects related the onset of their symptoms to
      antecedent facial beauty treatment, we decided to study the clinical and
      histologic profile of these patients. METHODS: Thirty seven subjects (36 women
      and one man) were questioned in detail about their acneiform eruptions. The
      patients were examined and a biopsy of typical lesions was taken in eight
      patients. RESULTS: On direct questioning, all patients related the onset of their
      lesions to facial beauty treatment taken 3-8 weeks previously. The predominant
      types of lesion were deep-seated nodules, although a few closed comedones were
      present in some cases. Most lesions took a long time to heal and, on healing,
      left behind hyperpigmentation. The cheeks were universally involved in all
      patients, and the chin and forehead were involved in 14. The histopathologic
      study revealed a predominantly peri-appendageal dermal infiltrate consisting of
      lymphocytes and histiocytes admixed with polymorphs. A granulomatous infiltrate
      was seen in one-third of the biopsies. CONCLUSIONS: This eruption is unlike the
      earlier eruption described as acne cosmetica in being inflammatory, indolent, and
      often occurring after the first cream massage itself.

PMID- 10208617
TI  - The hyperkeratotic variant of disseminated superficial actinic porokeratosis
      (DSAP).
AB  - A 78-year-old South Korean man was referred to us from the Medical Intensive Care
      Unit (MICU) for an opinion. He was comatose and was on ventilatory care due to
      aspiration pneumonia. Multiple tiny papules had developed 10 years previously and
      since then the number and size had been increasing gradually. He had been
      diabetic for the past 4 years, and had Parkinson's disease diagnosed 1 year
      previously. Laboratory examinations revealed an elevated level of white blood
      cells (WBCs) (25,000/microL) and decreased hemoglobin (8.8 g/dL). Other
      laboratory results were negative or within normal limits. Skin examination showed
      multiple, discrete, crust-like, brownish papules over the erythematous base on
      the face, upper extremities, and lower extremities. With the clinical impressions
      of irritated verruca vulgaris, seborrheic keratosis, or cutaneous fungal
      infection, a skin biopsy was taken from a papule on the left shin, and
      histopathologic examination revealed several pronounced hyperkeratotic and
      parakeratotic columns, and characteristic cornoid lamellae in the stratum
      corneum. Beneath the cornoid lamellae, the granular layer was decreased. A number
      of round or oval, dyskeratotic, homogenized eosinophilic cells with pyknotic
      nuclei were scattered in the prickle cell layer below the cornoid lamellae. A
      mild lymphohistiocytic infiltrate was observed in the papillary dermis and around
      the blood vessels in the upper dermis. Also, actinic degeneration was present in
      the upper dermis.

PMID- 10208618
TI  - Erythroderma with pemphigus immunofluorescence. An erythrodermic variant of
      pemphigus?

PMID- 10208619
TI  - Peeling skin syndrome.

PMID- 10208620
TI  - An infant with multiple hemangiomas showing favorable prognosis.

PMID- 10208621
TI  - Treatment outcome of acne vulgaris with oral isotretinoin in 89 patients.

PMID- 10208622
TI  - Pemphigus vulgaris: benefits of tetracycline as adjuvant therapy in a series of
      thirteen patients.
AB  - BACKGROUND: Tetracycline is an antibiotic which has been proven beneficial as an
      immunomodulating drug in the treatment of autoimmune bullous diseases. METHODS:
      Thirteen hospitalized patients with pempigus vulgaris received tetracycline 2
      g/day for 1 month, then 1 g/day for the following 4 weeks. Prednisone 0.5-1
      mg/kg/day was then gradually reduced. The control group consisted of seven
      patients with pemphigus who had received prednisone and azathioprine. RESULTS: A
      total of 13 patients in the study group achieved cessation of new blister
      formation within 5.4 days, compared to 23.71 days (p < 0.0001). The average
      initial dose of prednisone was 76.53 mg/day for the study group and 118.57 mg/day
      in the control group (p < 0.014). The average number of days before reduction of
      the prednisone dosage could begin was 16.53 days for the study group compared to
      31.28 days in the control (p < 0.049). Total hospitalization time was also
      significantly lower: 34.07 days (p < 0.001). The clinical response was not linked
      to the location of lesions nor to severity of disease. CONCLUSIONS: Tetracycline
      was shown to be effective as an adjuvant therapy for pemphigus with low toxicity
      and safety.

PMID- 10208623
TI  - Early work on syphilis: Diaz de Ysla's treatise on the serpentine disease of
      Hispaniola Island.

PMID- 10208624
TI  - Keloid formation induced by isotretinoin therapy.

PMID- 10208625
TI  - Cyclosporin A-induced hair darkening.

PMID- 10208626
TI  - Prick test and protein contact dermatitis.

PMID- 10208627
TI  - CD4+ T-lymphocytopenia, Kaposi's sarcoma, HHV-8 infection, severe seborrheic
      dermatitis, and onychomycosis in a homosexual man without HIV infection.

PMID- 10208628
TI  - Toxic epidermal necrolysis following treatment with oxaprozin.

PMID- 10208629
TI  - Solar urticaria as the presenting sign of hypereosinophilic syndrome.

PMID- 10208630
TI  - Another look at ivermectin in the treatment of scabies and head lice.

PMID- 10208631
TI  - Is ivermectin safe for humans?

PMID- 10208632
TI  - Unilateral linear trichoepitheliomas.

PMID- 10208633
TI  - Pachydermodactyly.

PMID- 10208634
TI  - Repigmentation of vitiligo patches by transplantation of hair follicles.

PMID- 10208635
TI  - The development of rheumatoid arthritis in a patient with lichen sclerosus et
      atrophicus.

PMID- 10208636
TI  - Genes for human arylamine N-acetyltransferases in relation to loss of the short
      arm of chromosome 8 in bladder cancer.
AB  - Polymorphisms of N-acetyltransferase type 2 (NAT2) conferring the slow acetylator
      phenotype have been linked to increased susceptibility to arylamine-induced
      bladder cancer in Caucasians. Genes for NAT2, the other NAT isozyme, NAT1, and a
      NAT pseudogene (NATP) are found on 8p22, a region displaying loss of
      heterozygosity, particularly in invasive bladder tumours. A restriction enzyme
      digestion map has defined the relative positions of the NAT genes to each other
      and to adjacent CpG islands. NAT2, as a polymorphic gene of known function, is a
      potentially valuable marker for the detection of loss of heterozygosity in 8p22.
      Two approaches to investigate loss of heterozygosity at the NAT2 locus in bladder
      tumours have been used. (1) A cosmid containing NAT2 has been used in
      fluorescence in-situ hybridization on human exfoliated bladder cells collected
      from unselected bladder cancer outpatients. Loss of signal from the NAT2 cosmid
      was found in nine of the 20 patients. (2) A panel of 13 human bladder tumours was
      investigated for loss of heterozygosity using the polymorphism in the NAT2 gene
      as a marker. Loss of heterozygosity at the NAT2 locus has been compared with loss
      of heterozygosity at adjacent microsatellite marker sites known to be located on
      8p. There is agreement between loss of heterozygosity at the NAT2 locus and
      adjacent microsatellite marker loci in 11 of the tumours but two of the tumours
      appear to show retention at the NAT2 locus. More extensive mapping of the region
      around the NAT loci, particularly on the centromeric side, is important to
      pinpoint possible tumour suppressor genes or their modifiers in the region. There
      are no other expressed sequences known in this region and therefore NAT genes are
      important genetic landmarks.

PMID- 10208637
TI  - N-acetyltransferase (NAT2) genotype and susceptibility of sporadic Alzheimer's
      disease.
AB  - The importance of environmental aggression and individual susceptibility to
      develop Alzheimer's Disease (AD) has been suggested by epidemiological studies on
      both typical familial and sporadic AD cases. In order to elucidate functions that
      can influence the susceptibility to AD pathogenesis, we genotyped a group of 53
      sporadic late-onset AD patients, matched control individuals and a larger
      randomly selected non-demented population for the N-acetyltransferase (NAT2). We
      determined the relative frequencies of individual allele combinations that define
      a broad range of acetylator phenotypes. Inter-individual variability in the
      cytotoxic and genotoxic responses to a wide diversity of environmental chemicals
      is known to result from the polymorphism of NAT2 as well as other drug
      metabolizing-enzyme genes. The results presented are the first to demonstrate a
      significant difference in the NAT2 genotype profiles of sporadic AD patients
      compared with the healthy population. A lower frequency of the recessive alleles
      NAT2*6 (chi-squared 1 d.f. = 12.56, P < 0.0004) and NAT2*5B (chi-squared 1 d.f. =
      6.72, P < 0.01) was found among the AD population compared with control
      individuals, which was concomitant with a significantly higher number of NAT2*4
      fully active allele homozygotes and heterozygotes (chi-squared 1 d.f. = 5.69, P =
      0.017). The most notable observation was the absence of NAT2*5B/NAT2*6
      heterozygotes among cases while being present in 22.5% of control individuals
      (chi-squared 1 d.f. = 13.08, P = 0.0003). These observations indicate that NAT2
      is a potential low-penetrance gene in AD pathogenesis, determining an individual
      susceptibility trait predisposing to this degenerative disease.

PMID- 10208638
TI  - Analysis of neuroleptic binding affinities and potencies for the different human
      D2 dopamine receptor missense variants.
AB  - Neuroleptics, or antipsychotics, are widely used for the treatment of psychotic
      symptoms such as hallucinations and delusions in schizophrenia and other
      psychiatric disorders. Pharmacotherapy of these diseases is frequently
      complicated by a great variability in the clinical response to neuroleptics and
      by the development of serious and potentially life-threatening side-effects.
      Brain D2 dopamine receptors are one of the major targets of neuroleptic
      treatment. The human D2 dopamine receptor (DRD2) gene has three variants
      predicting the amino acid substitutions Ser311Cys, Pro310Ser and Val96Ala in the
      receptor protein. We show that several typical and atypical neuroleptics commonly
      used in the treatment of psychotic disorders have differences in binding
      affinities and potencies for the D2 dopamine receptor variants. Functional
      differences between dopamine receptor variants might be related to genetically
      determined differences in response to neuroleptic treatment.

PMID- 10208639
TI  - Polymorphism of the human alcohol dehydrogenase 4 (ADH4) promoter affects gene
      expression.
AB  - The human alcohol dehydrogenase 4 gene (ADH4) encodes the human pi-alcohol
      dehydrogenase (pi-ADH), which can contribute to ethanol metabolism at moderate
      and high concentrations of ethanol. There are no known structural variants of pi
      ADH in humans. We report the first polymorphisms in the ADH4 gene, at three sites
      in the promoter: -192 bp, -159 bp and -75 bp, respectively. To determine whether
      these variations affected promoter function, different haplotypes of the ADH4
      proximal promoter were subcloned into a luciferase reporter vector, and the
      relative promoter activity analysed in hepatoma cells. One of the three sites had
      a dramatic effect on promoter activity, while the others did not detectably
      affect activity. The -75A allele had promoter activity more than twice that of
      the -75C allele. Alcohol dehydrogenase activity is rate limiting for ethanol
      oxidation. We hypothesize that the different ADH4 alleles lead to different
      amounts of pi-ADH in liver, which affects the risk for alcoholism by modulating
      alcohol metabolism.

PMID- 10208640
TI  - CYP2D6 is associated with Parkinson's disease but not with dementia with Lewy
      Bodies or Alzheimer's disease.
AB  - The similarities between the clinical and pathological findings of dementia with
      Lewy Bodies (DLB) with Alzheimer's disease and Parkinson's disease are complex,
      and their significance for pathogenesis is unresolved. It is likely that DLB
      shares common disease determinants with both Alzheimer's disease and Parkinson's
      disease. Clinically DLB shows the presence of dementia similar, though not
      identical, to that found in Alzheimer's disease. A parkinsonian movement disorder
      is present in a proportion of DLB cases. Pathologically DLB shows senile plaques,
      as with Alzheimer's disease, and also substantia nigra neurone loss and Lewy
      bodies, as with Parkinson's disease. At a genetic level, DLB shows an elevated
      Apolipoprotein E epsilon4 frequency as described in Alzheimer's disease, but this
      is absent in Parkinson's disease. An elevated frequency of the CYP2D6*4 allele
      has been found in Parkinson's disease and we have therefore genotyped a large
      series of clinically and neuropathologically confirmed cases of DLB, Alzheimer's
      disease, Parkinson's disease and age-matched control individuals for the CYP2D6*4
      allele. Whilst an elevated frequency of the CYP2D6*4 allele was found in
      Parkinson's disease, no such elevations were found in DLB or Alzheimer's disease.
      Stratification of the CYP2D6*4 allele with respect to the Apolipoprotein E
      epsilon4 also did not show any significant associations with the CYP2D6*4 allele.
      The CYP2D6*4 allele is not a major genetic determinant of DLB and the results
      place DLB with Alzheimer's disease rather than Parkinson's disease on a genetic
      level.

PMID- 10208641
TI  - The frequency and distribution of thiopurine methyltransferase alleles in
      Caucasian and Asian populations.
AB  - Thiopurine methyltransferase metabolizes 6-mercaptopurine, thioguanine and
      azathioprine, thereby regulating cytotoxicity and clinical response to these
      thiopurine drugs. In healthy Caucasian populations, 89-94% of individuals have
      high thiopurine methyltransferase activity, 6-11% intermediate and 0.3% low,
      resulting from genetic polymorphism. Four variant thiopurine methyltransferase
      alleles were detected in over 80% of individuals with low or intermediate
      thiopurine methyltransferase activity. The wild-type allele is defined as TPMT*1
      and the mutant alleles are TPMT*2 (G238C), TPMT*3A (G460A and A719G), TPMT*3B
      (G460A) and TPMT*3B (A719G). The frequency of these alleles in different ethnic
      groups is not well defined. In this study, DNA from 199 British Caucasian, 99
      British South West Asian and 192 Chinese individuals was analysed for the
      presence of these variant alleles using polymerase chain reaction-restriction
      fragment length polymorphism and allele-specific polymerase chain reaction based
      assays. The frequency of individuals with a variant thiopurine methyltransferase
      genotype was: Caucasians 10.1% (20/199), South West Asians 2.0% (2/99) and
      Chinese 4.7% (9/192). Two TPMT*2 heterozygotes were identified in the Caucasian
      population, but this allele was not found in the two Asian populations. TPMT*3A
      was the only mutant allele found in the South West Asians (two heterozygotes).
      This was also the most common mutant allele in the Caucasians (16 heterozygotes
      and one homozygote) but was not found in the Chinese. All mutant alleles
      identified in the Chinese population were TPMT*3C (nine heterozygotes). This
      allele was found at a low frequency in the Caucasians (one heterozygote). This
      suggests that A719G is the oldest mutation, with G460A being acquired later to
      form the TPMT*3A allele in the Caucasian and South West Asian populations. TPMT*2
      appears to be a more recent allele, which has only been detected in Caucasians to
      date. These ethnic differences may be important in the clinical use of thiopurine
      drugs.

PMID- 10208642
TI  - The effect of genetic polymorphisms in CYP2C9 on sulphamethoxazole N
      hydroxylation.
AB  - Sulphamethoxazole undergoes CYP2C9-mediated bioactivation to a hydroxylamine. In
      this study, we investigated the effect of the CYP2C9Arg144 to Cys (CYP2C9*2) and
      CYP2C9Ile359 to Leu (CYP2C9*3) polymorphisms on sulphamethoxazole N
      hydroxylation. Human livers were genotyped using polymerase chain reaction
      amplification and restriction fragment length polymorphism analysis. Formation of
      sulphamethoxazole hydroxylamine and methylhydroxy tolbutamide in microsomes
      prepared from cell lines and the genotyped human livers was determined by high
      pressure liquid chromatography. Microsomes prepared from the cell line expressing
      the allelic variants CYP2C9-Cys144 and CYP2C9-Leu359 displayed a threefold and 20
      fold decrease in intrinsic clearance (Cl(int)) for sulphamethoxazole,
      respectively, when compared with the wild-type, CYP2C9-Arg144. A significant
      decrease (P < 0.05) in Cl(int) was also observed with tolbutamide for both
      mutations. Of the 26 human livers genotyped, 61.5% were homozygous wild-type,
      26.9% were heterozygotes for CYP2C9*2 and 15.4% were heterozygotes for CYP2C9*3.
      No homozygous mutant livers were detected. There was a good correlation between
      sulphamethoxazole N-hydroxylation and tolbutamide methyl hydroxylation (r =
      0.825). However, there was no difference in the kinetic parameters for either
      sulphamethoxazole N-hydroxylation or tolbutamide methyl hydroxylation between the
      wild type livers (n = 6) and either the livers heterozygous for the CYP2C9*2 (n =
      5) or the livers heterozygous for the CYP2C9*3 mutation (n = 3). The CYP2C9*2 and
      CYP2C9*3 polymorphisms may have some influence on the bioactivation of
      sulphamethoxazole, particularly in individuals who are homozygous mutants, and
      this could act as a protective factor against sulphamethoxazole hypersensitivity.
      However, given the rarity of homozygous mutants, it is likely that other
      metabolic and immunological risk factors will dominate individual susceptibility.

PMID- 10208643
TI  - The stereoselective metabolism of fluoxetine in poor and extensive metabolizers
      of sparteine.
AB  - The selective serotonin reuptake inhibitor fluoxetine is administered as a
      racemic mixture, and R- and S-fluoxetine are metabolized in the liver by N
      demethylation to R- and S-norfluoxetine, respectively. R- and S-fluoxetine and S
      norfluoxetine are equally potent selective serotonin reuptake inhibitors, but R
      norfluoxetine is 20-fold less potent in this regard. Racemic fluoxetine and
      norfluoxetine are potent inhibitors of cytochrome P450 (CYP) 2D6 in vivo and in
      vitro and recent studies in vivo have shown that racemic fluoxetine is
      metabolized by CYP2D6. The primary aim of the present study was to investigate
      the stereoselective metabolism of fluoxetine and norfluoxetine by CYP2D6 in vivo.
      A single oral dose of fluoxetine (60 mg) was administered to six poor and six
      extensive metabolizers of sparteine. Blood samples were collected during 6 weeks
      for poor metabolizers and 3 weeks for extensive metabolizers. Once a week a
      sparteine test was performed. The R- and S-enantiomers of fluoxetine and
      norfluoxetine were determined by a stereoselective gas chromatography-mass
      spectroscopy method. In the poor metabolizers, the oral clearance of R- and S
      fluoxetine was 3.0 l/h and 17 l/h, respectively, the corresponding values in the
      extensive metabolizers were 36 l/h and 40 l/h, respectively. For both
      enantiomers, the phenotype difference was statistically significant. In poor
      metabolizers, the elimination half-lives were 6.9 days and 17.4 days for R- and S
      norfluoxetine, respectively, and in the extensive metabolizers it was 5.5 days
      for both enantiomers, a significant phenotypical difference only for S
      norfluoxetine. For fluoxetine the elimination half-lives were 9.5 and 6.1 days in
      poor metabolizers for the R- and S-enantiomer, respectively. The corresponding
      values in the extensive metabolizers were 2.6 and 1.1 days, respectively. Also
      for this parameter, the differences were statistically significant. This study
      shows that CYP2D6 catalyses the metabolism of R- and S-fluoxetine and most likely
      the further metabolism of S-norfluoxetine but not of R-norfluoxetine.

PMID- 10208644
TI  - High yield purification and characterization of engineered human P450 1A2 and
      generation of immuno-inhibitor antibodies.
AB  - P450 S12, an engineered human P450 1A2 containing the 88-first amino-acids of the
      P450 1A1, demonstrates particularly high expression level in yeast while
      exhibiting catalytic properties very similar to the moderately expressed natural
      human P450 1A2. To facilitate P450 purification by nickel chelate chromatography,
      C-terminal extensions including histidine tags were tested. The -G(H)4 extension
      was found to be particularly efficient for permitting high expression levels
      without any catalytic alteration. This engineered P450 was purified to
      electrophoretic homogeneity (18 nmol/mg of protein) at a very high yield (87%)
      without any detectable formation of P420. P450 S12 activities were reconstituted
      in the presence of yeast and Arabidopsis thaliana (ATR1) NADPH-P450 reductases.
      The plant reductase supported better ethoxyresorufin-, methoxyresorufin- and
      phenacetin-O-dealkylase activities than the yeast reductase in reconstituted
      systems. Interestingly, polyclonal antibodies raised against purified P450 S12
      selectively recognized in Western blot and fully immuno-inhibited the natural or
      recombinant P450 1A2 with very limited or no cross-reaction with P450 1A1 and
      other isoenzymes.

PMID- 10208645
TI  - Pharmacokinetics of chlorpheniramine, phenytoin, glipizide and nifedipine in an
      individual homozygous for the CYP2C9*3 allele.
AB  - Genetic polymorphisms in the cytochrome P450 (CYP) family are widely known to
      contribute to interindividual differences in the pharmacokinetics of many drugs.
      Several alleles for the CYP2C9 gene have been reported. Individuals homozygous
      for the Leu359 variant (CYP2C9*3) have been shown to have significantly lower
      drug clearances compared with Ile359 (CYP2C9*1) homozygous individuals. A male
      Caucasian who participated in six bioavailability studies in our laboratory over
      a period of several years showed extremely low clearance of two drugs: phenytoin
      and glipizide (both substrates of CYP2C9), but not for nifedipine (a CYP3A4
      substrate) and chlorpheniramine (a CYP2D6 substrate). His oral clearance of
      phenytoin was 21% of the mean of the other 11 individuals participating in the
      study, and his oral clearance of glipizide, a second generation sulfonylurea
      structurally similar to tolbutamide, was only 188% of the mean of the other 10
      individuals. However, his oral clearance of nifedipine and chlorpheniramine did
      not differ from individuals in other studies performed at our laboratories. An
      additional blood sample was obtained from this individual to determine if he
      possessed any of the known CYP2C9 or CYP2C19 allelic variants that would account
      for his poor clearance of the CYP2C9 substrates (phenytoin and glipizide)
      compared with the CYP3A4 (nifedipine) and CYP2D6 (chlorpheniramine) substrates.
      The results of the genotype testing showed that this individual was homozygous
      for the CYP2C9*3 allele and did not possess any of the known defective CYP2C19
      alleles. This study establishes that the Leu359 mutation is responsible for the
      phenytoin and glipizide/tolbutamide poor metabolizer phenotype.

PMID- 10208646
TI  - Genetic polymorphism of human O6-alkylguanine-DNA alkyltransferase:
      identification of a missense variation in the active site region.
AB  - O6-Alkylguanine-DNA alkyltransferase (AGT, EC 2.1.1.63) is a principle DNA repair
      protein in repairing O6-alkylguanine in DNA, a major premutagenic lesion produced
      by environmental and therapeutic alkylating agents. AGT plays a critical role in
      protecting cells against mutation and cytotoxicity induced by these alkylating
      agents. The existence of a large interindividual variation in human AGT activity
      level has been observed and we hypothesize that genetic polymorphism of AGT could
      be an important determinant for this variation. The present study reports the
      identification of a novel missense polymorphism in the human AGT gene. The
      polymorphic alteration occurs at codon 143 in exon 5, converting isoleucine (ATC)
      to valine (GTC). Because Ile143 is adjacent to the alkyl acceptor Cys145 of the
      AGT active site and is conserved among mammalian AGTs, amino acid substitution at
      this position may affect the function of AGT. The codon 143 polymorphism appears
      to be linked to another new polymorphic alteration at codon 178, which converts
      lysine (AAG) to arginine (AGG). Because it has been reported that human AGT can
      be truncated at position 176 without loss of activity, the codon 178 polymorphism
      may not affect AGT activity. The codon 143/178 polymorphism was found in two of
      90 (2%) esophageal cancer patients residing in a high incidence area of China,
      but was not detected in 60 normal individuals residing in the same area. Six of
      28 (210%) non-cancer Caucasian individuals, however, were found to carry this
      polymorphic allele, suggesting a significant ethnic difference in distribution of
      this codon 143/178 polymorphism between Chinese and Caucasian individuals. In
      addition, we confirmed the existence of a codon 84 genetic polymorphism
      previously identified in a Japanese population, which converts leucine (CTT) to
      phenylalanine (TTT). The distribution of codon 84 polymorphism was 16%, 20% and
      36%, respectively, in the Chinese esophageal cancer patients, Chinese and
      Caucasian non-cancer individuals. Coexistence of codons 84 and 143/178
      polymorphic alterations was found in one Caucasian individual. In all the Chinese
      (n = 150) and Caucasian (n = 28) samples examined, we were unable to detect a
      previously reported codon 160 polymorphism (Gly to Arg) which occurred in 10-25%
      of the Japanese individuals and was shown to affect the reaction of AGT with the
      drug O6-benzylguanine. The functional significance of the codon 143/178 genetic
      polymorphism of human AGT and its role in determining an individual's
      susceptibility to environmental alkylating carcinogens and response to alkylating
      chemotherapeutic drugs both remain to be studied.

PMID- 10208647
TI  - Detection of the GSTM1*0 allele by long polymerase chain reaction.
AB  - Approximately 50% of individuals in most human populations completely lack
      activity of the detoxifying enzyme glutathione S-transferase M1. The medical
      consequences of this deficiency have been extensively investigated in molecular
      epidemiological studies, but possible differences of the highly active homozygous
      genotype versus the moderately active heterozygous genotype could not be
      considered because many currently used polymerase chain reaction (PCR) assays
      cannot distinguish the homozygous genotypes GSTM1 *A/A and GSTM1*B/B from the
      heterozygous genotypes GSTM1*A/0 and GSTM1*B/0. Here, we describe that long PCR
      is suitable for this purpose by specifically producing a signal for the GSTM1*0
      allele. Based on the published cluster of GSTM genes (GSTM1 to -M5), a 13-kb
      segment spanning the site of the GSTM1 deletion was amplified using a GSTM2
      specific forward primer (5'-CATCGCTTATGATGTCCTTGAGAGAAACCAAG-3') and a reverse
      primer, which is specific for the upstream region of GSTMS (5'
      GCGTTTCTGAGGACTGGACTGATGATCG-3'). Any failure in the amplification was controlled
      by co-amplification of a 15-kb human tissue plasminogen activator gene fragment.
      The GSTM1*0-specific 13-kb amplicon appears in all carriers of one or two null
      alleles, but in none of the 14 tested GST1*A/B samples which served as controls
      since individuals with this genotype are known to lack any GSTM1*0 allele. While
      conventional PCR assays for detection of the GSTM1 deletion differentiated
      homozygously deficient from hetero- or homozygously active individuals, this long
      PCR assay differentiates homozygously active from hetero- or homozygously
      deficient individuals. Using both assays, an unambiguous differentiation into
      carriers of zero, one or two active alleles of GSTM1 is possible.

PMID- 10208648
TI  - Modified ligand binding to the naturally occurring Cys-124 variant of the human
      serotonin 5-HT1B receptor.
AB  - A substitution of phenylalanine by cysteine in position 124 is the only known
      naturally occurring variant of the human 5-HT1B (h5-HT1B) receptor. The present
      study was designed to evaluate the potential influence of the Cys-124 variant on
      pharmacological properties of the receptor and to test for an involvement of the
      mutation in the genetic predisposition to schizophrenia or bipolar affective
      disorder. Binding of [3H]5-carboxamidotryptamine ([3H]5-CT) and its competition
      with serotonin receptor agonists and antagonists were determined in COS-7 cells
      transfected with the wild-type or the variant h5-HT1B receptor cDNA. In
      saturation experiments with [3H]5-CT, the maximum binding (Bmax) of the variant
      receptor was approximately 30% of the wild-type receptor. In competition
      experiments with 1 nM [3H]5-CT, the following serotonin receptor ligands
      exhibited a two to three times higher affinity for the mutant than for the wild
      type receptor: dihydroergotamine, L-694,247, SB-216641, 5-CT, 5-HT, sumatriptan,
      RU24969 and methysergide (compounds listed at decreasing order of potency at the
      wild-type receptor). In contrast, the serotonin receptor antagonist ketanserin
      exhibited higher binding affinity for the wild-type than for the mutant h5-HT1B
      receptor and GR127939, (-)propranolol and BRL-15572 showed equal affinity for
      both types of receptor. Mutation screening of schizophrenic and bipolar patients
      revealed no relationship between the variant receptor and development of disease.
      In conclusion, our data suggest that the Cys-124 variant significantly affects
      the pharmacological properties of the h5-HT1B receptor. Carriers of the variant
      may exhibit differences in response to drugs acting on the h5-HT1B receptor or
      may develop side-effects to such agents.

PMID- 10208649
TI  - Association of arylamine N-acetyltransferases NAT1 and NAT2 genotypes to
      laryngeal cancer risk.
AB  - Genetically polymorphic xenobiotic metabolizing enzymes are supposed to be host
      factors for an individual's cancer susceptibility. A total of 255 laryngeal
      cancer patients was genotyped for NAT1 and NAT2 and compared with 510 reference
      individuals, matched by age and gender. NAT1 genotypes (NAT1*3, *4, *10, and *11
      ) were found equally distributed between cases and control individuals. However,
      there was a significant overrepresentation of 20 (7.8%) homozygous NAT2 genotypes
      coding for rapid acetylation (NAT2*4/*4 and NAT2*4/*12A) amongst laryngeal cancer
      patients versus 19 (3.7%) such individuals in the control group (odds ratio 2.18,
      95% confidence limits 1.13, 4.22; P = 0.018). Furthermore, an increasing
      NAT2*4/*4 frequency in cases with strong cigarette consumption was observed, but
      also in non-smokers. Heterozygous genotypes of NAT2*4/slow were not
      overrepresented. These results correspond with earlier findings in lung cancer.
      Analysis of NAT1 and NAT2 combinations revealed a linkage disequilibrium between
      NAT1*10 and NAT2*4; NAT1*10 frequency was twofold higher in NAT2*4/*4 carriers
      than in slow NAT2 coding genotypes. In conclusion, the distinct genotype
      NAT2*4/*4 proved to be a rare, but powerful host risk factor for larynx
      carcinoma. These data support the notion that an individual's specific NAT2
      genotype may be decisive for the organ of his smoking-initiated cancer.

PMID- 10208650
TI  - Genotype-phenotype relationships in studies of a polymorphism in NAD(P)H:quinone
      oxidoreductase 1.
AB  - The NAD(P)H:quinone oxidoreductase 1 (NQO1) genotype-phenotype relationship was
      examined in individuals with a polymorphism in NQO1. The polymorphism comprises a
      C to T base change at position 609 of the human NQO1 cDNA (C609T) and codes for a
      proline to serine substitution in the amino acid structure of the NQO1 protein.
      Genotyping was performed by polymerase chain reaction-restriction fragment length
      polymorphism analysis of genomic DNA. Phenotyping was performed using enzyme
      activity assays and/or immunoblotting of human tumor cell lines and of saliva and
      bone marrow samples from healthy donors. Phenotyping of uninvolved lung and lung
      tumors from archived biopsy material was performed by immunohistochemistry. NQO1
      activity and protein could be detected in wild-type (C/C) human tumor cells (HT
      29) under conditions where NQO1 protein could not be detected in cells (BE)
      homozygous for the C609T change (T/T). Trace levels of NQO1 protein could be
      detected in BE cells; however, when immunoblots were subjected to
      chemiluminescence detection for prolonged periods. In saliva samples from 11
      individuals carrying the homozygous C609T change (T/T), no NQO1 protein could be
      detected even after prolonged chemiluminescence detection. The amount of NQO1
      protein present in saliva was quantified and found to be significantly less in
      heterozygous individuals (C/T) than in wild-type individuals (C/C). In bone
      marrow stromal cultures, both NQO1 activity and protein could be detected in
      heterozygotes (C/T) and in wild-type (C/C) samples. In a bone marrow stromal
      culture from an individual genotyped as T/T at position 609, no NQO1 protein or
      activity could be detected. NQO1 is elevated in non-small cell lung cancers and
      could be readily observed as intense immunostaining throughout lung
      adenocarcinomas genotyped as C/C but no immunostaining could be detected in
      adenocarcinomas genotyped as T/T at position 609. NQO1 is expressed in normal
      human lung but is localized to respiratory epithelium and to vascular
      endothelium. In normal lung tissue from individuals genotyped as T/T, no or faint
      immunostaining for NQO1 could be detected in either respiratory epithelium or
      vascular endothelium. These results demonstrate that tissues from individuals
      homozygous for the C609T change have no detectable or, at best, only trace
      amounts of NQO1 protein and are devoid of NQO1 activity.

PMID- 10208651
TI  - Pitfalls in N-acetyltransferase 2 genotyping.
AB  - In recent times, an increasing number of different haplotypes of the arylamine N
      acetyltransferase 2 gene are reported. Since most of the various alleles are
      defined by linkages of commonly known hereditary point mutations, some confusion
      may occur when the mutation pattern revealed by genotyping should be addressed
      correctly to defined haplotypes. Moreover, problems take place when different
      nomenclatures are incorrectly transferred. To meet growing concerns regarding
      exact NAT2 genotyping and correct nomenclature, we summarized typical pitfalls in
      methodologies and terminologies. NAT2 genotypes containing rare alleles, or even
      combinations of them, should always be checked critically for possible laboratory
      failures. Novel alleles should be best verified by subcloning or other adequate
      methodologies. For prediction of the acetylator phenotype it seems generally
      sufficient to genotype NAT2 mutations C282T and T341C. In African populations,
      however, it is necessary to check additionally for the frequent G191A mutation,
      which codes also for a slow acetylator variant.

PMID- 10208652
TI  - Partial characterization of a human zinc-deficiency syndrome by differential
      display.
AB  - The effect of the acrodermatitis enteropathica mutation (AE) on gene expression
      was investigated using differential display. Two differentially expressed cDNAs
      were partially characterized. The NA8 cDNA (HT11A anchor and HAP 8 random primer
      pair) was expressed in greater quantity in normal fibroblasts, was 249 bp, and
      hybridized to three mRNA species (2 kb, 1 kb, 0.8 kb). Northern blot analysis
      indicated that the relative amounts of the AE mRNA species were reduced by 73%,
      75%, and 52%, respectively. The cDNA sequence exhibited 92-93% homology to the
      human cytochrome oxidase subunit II, as analyzed through the GenBank database.
      The AEG4 cDNA species (HT11G anchor and HAP 4 random, primer pair) was expressed
      in greater quantity in AE fibroblasts, was 197 bp, and hybridized to two mRNA
      species (9 kb, 4 kb). Northern blot analysis indicated that the 9-kb mRNA species
      was present equally in AE and normal cells, but the 4-kb mRNA species was only
      present in the AE fibroblasts. The cDNA sequence exhibited 92% homology to LINE1
      human retrotransposons, as analyzed through the GenBank database. The functional
      relationship between the mutation and the reduced expression of cytochrome
      oxidase subunit II is unknown at this time and needs to be addressed. The
      increased expression of the LINE1 element in AE fibroblasts may be indicative of
      an insertion mutation affecting the mRNA of a protein involved in zinc transport,
      a prospect which requires further investigation.

PMID- 10208653
TI  - Essential metal ions alter the lactoferrin binding to the erythrocyte plasma
      membrane receptors.
AB  - The effect of metal ions at a concentration of 10(-8) to 10(-5) M [using their
      salts: ZnCl2, CdCl2, LiCl, CuSO4, NiSO4, Al2(SO4)3, (NH4)2MoO4 on the lactoferrin
      (Lf) binding to the erythrocyte membrane receptors was studied. In the absence of
      metal ions, Scatchard's analysis showed the existence of two kinds of binding
      site: one with high affinity and low capacity, and the another with low affinity
      and high capacity. All these metals, excluding Zn2+ and Cd2+, at a concentration
      10(-5) M decreased the affinity of Lf binding (Ka1) to the high-affinity
      receptors. In the presence of Zn2+ and Cd2+, only the low-affinity binding site
      was found. Significant inhibition on the affinity (Ka2) of the low-affinity class
      of receptors showed Zn2+, Al3+, and Mo6+. Depending on their concentration (10(
      8)-10(-5) M), these ions enhanced to a different extent, the binding capacity of
      the both types receptors, but the effect did not correspond to the applied doses.
      Several explanations of the mechanism for influence of the metal ions on the Lf
      receptor interaction is discussed.

PMID- 10208654
TI  - Dietary zinc intake of a group of long-stay mentally handicapped women: some
      bioavailability considerations.
AB  - Dietary factors affecting zinc bioavailability were evaluated according to their
      relative distribution in the individual daily meals making up the basic diet of
      17 institutionalized, mentally handicapped adult women. Mean intake values of
      zinc, phytate, nonstarch polysaccharides (NSP), calcium, protein, and energy were
      calculated from a dietary survey of 7 consecutive days, which also served to
      obtain values for the two zinc bioavailability predictor formulas, phytate/Zn
      millimolar ratio and [Ca][phytate]/[Zn][energy] ratio. Mean daily zinc intake was
      8.5 +/- 1.8 mg, with noon and evening meals accounting for the highest
      contribution to this value (45% and 35%, respectively), whereas breakfast meals'
      contribution was 16%. The mean protein intake was 55 +/- 13 g, with noon and
      evening meals being the major contributors to total daily intake (42% and 38%,
      respectively). Breakfast meals accounted for 77% of daily phytate intake, giving
      a respective phytate/Zn millimolar ratio of 20.4 +/- 7.6 and a
      [Ca][phytate]/[Zn][energy] ratio of 336 +/- 127 mmol/Mcal. Values for both ratios
      based on noon and evening meals were negligible in comparison. The mean daily NSP
      intake was 9.8 +/- 4.2 g, with 53% of total daily intake supplied from breakfast
      meals, whereas noon and evening meals accounted for 30% and 14%, respectively.
      The results, while suggesting that zinc bioavailability is unlikely to be
      adversely affected, indicated that dietary fiber intake levels are probably
      inadequate, particularly in view of the nonambulant condition and low physical
      activity prevalent in such individuals, who may, as a consequence, be susceptible
      to health disorders associated with impaired bowel function and constipation.

PMID- 10208655
TI  - Relative and combined effects of ethanol and protein deficiency on strontium and
      barium bone content and fecal and urinary excretion.
AB  - Strontium metabolism has attracted considerable interest because of to its
      interaction with calcium, the bone alterations detected after treatment with
      strontium, and its potential value as a paleodietary indicator. The effects of
      ethanol on strontium and barium metabolism-another divalent cation which also
      accumulates in bone--is largely unknown. Based on this fact, we have determined
      bone content and fecal and urinary excretion of Ba and Sr in four groups of eight
      animals each pair-fed for 8 wk with (1) a nutritionally adequate diet, (2) a 36%
      (as energy) ethanol-containing isocaloric diet, (3) a 2% protein, isocaloric
      diet, and (4) a 36% ethanol, 2% protein isocaloric diet, following the Lieber
      DeCarli model. Five additional rats were fed with the control diet ad libitum. We
      have found that ethanol tends to decrease and a low protein diet to increase bone
      strontium content; the decrease in bone strontium in the ethanol-fed rats is
      accompanied by an increase in the absolute excretion of strontium in urine.
      Ethanol also decreases bone barium content, but the effect of ethanol on urinary
      barium excretion is opposite that of strontium, a decrease. Thus, we conclude
      that ethanol alters both barium and strontium metabolism and bone deposition.

PMID- 10208656
TI  - Effect of lithium on hepatic and serum elemental status under different dietary
      protein regimens.
AB  - Lithium carbonate at the dose level of 1.1 g/kg was administered in diet to
      normal (18% protein), low-protein- (LP; 8%) and high-protein (HP; 30% diet)-fed
      rats for a period of 1 mo. The LP diet resulted in a significant decrease in the
      hepatic levels of zinc, iron, copper, manganese, calcium, and serum levels of
      calcium and sodium. The HP diet caused a marked decrease in copper and calcium
      levels in liver, but an increase in potassium levels in serum was observed.
      Lithium treatment to normal rats led to a significant reduction in the hepatic
      contents of zinc, copper, potassium, calcium, and serum contents of potassium and
      sodium, whereas an elevation in serum contents of calcium was noticed.
      Administration of lithium to protein-deficient rats increased the hepatic
      concentration of manganese and serum concentration of calcium and the levels
      almost reached the normal limits. On the other hand, there was a marked
      depression in potassium contents in the serum of LP- as well as HP-fed rats
      following lithium treatment when compared to LP and HP groups, respectively.

PMID- 10208657
TI  - Tissue-specific antioxidant profiles and susceptibility to lipid peroxidation of
      the newly hatched chick.
AB  - The hatching process is characterized by a range of adaptive changes, and a newly
      hatched chick is considered as an intermediate stage between prenatal and
      postnatal development. The aim of the present study was to evaluate the
      characteristic relationships between tissue-specific fatty acid composition and
      antioxidant protection in newly hatched chicks. Liver, yolk sac membrane, heart,
      kidney, lung, and four brain regions (cerebrum, cerebellum, stem, and optic
      lobes) were collected. Fatty acid composition of total lipids and
      phosphoglycerides, alpha-tocopherol, lutein, ascorbic acid, reduced glutathione,
      and the activities of Mn- and Cu,Zn-superoxide dismutase (SOD) and Se-dependent
      and non-Se-glutathione peroxidase (GSH-Px), and catalase (CAT) were determined.
      The levels of Fe, Cu, Zn, and Mn as well as tissue susceptibility to lipid
      peroxidation were also studied. The tissues of the newly hatched chick showed
      distinctive features in fatty acid profiles, antioxidant accumulation, and
      susceptibility to lipid peroxidation. The brain clearly displayed the greatest
      susceptibility to spontaneous and Fe-stimulated lipid peroxidation, was highly
      unsaturated and contained very low levels of vitamin E, no detectable
      carotenoids, low GSH-Px, and low CAT activity. At the same time, the brain was
      characterized by high ascorbic acid concentration and comparatively high SOD
      activity. It was suggested that in postnatal development, antioxidant enzymes
      presumably play the major role in antioxidant protection of the chick tissues.

PMID- 10208658
TI  - Selenium content of milk and milk products of Turkey. II.
AB  - Selenium content of 1028 milk and milk products of Turkey are presented in this
      study. The selenium content of human milk (colostrum, transitional, and mature
      milk), various kinds of milk [cow, sheep, goat, buffalo, paper boxes (3%, 1.5%,
      0.012% fat), bottled milk, condensed milk (10% fat), mineral added milk (1.6%),
      and banana, strawberry, and chocolate milk] and milk products (kefir, yogurt,
      Ayran, various cheese, coffee cream, ice cream, butter, margarine, milk powder,
      and fruit yogurt) in Turkey were determined by a spectrofluorometric method. The
      selenium levels of cow milks collected from 57 cities in Turkey were also
      determined. Selenium levels in cow milk varied with geographical location in
      Turkey and were found to be lowest for Van and highest for Aksaray. The results
      [milk (cow, sheep, goat, buffalo and human) and milks products] were compared
      with literature data from different countries.

PMID- 10208659
TI  - Anterior craniofacial resection for malignant ethmoid tumors--a series of 91
      patients.
AB  - BACKGROUND: Anterior craniofacial resection is now recognized as the best
      treatment for ethmoid tumors involving the cribriform plate with or without
      invasion of anterior cranial fossa. METHODS: Ninety-one patients underwent an
      anterior craniofacial resection for ethmoid malignant tumors at the Milan Cancer
      Institute between 1987 and 1994. The patient population was divided into two
      sections (30 and 61 patients) based upon some important variants (type of
      craniotomy, antibiotic treatment, postoperative care). RESULTS: The mean age was
      53.4 years (range, 24 to 78 years). There were 62 men and 29 women. Forty-nine
      patients had a recurrence after previous treatments (surgery and/or
      radiotherapy). The subdivision by histology was as follows: 50 cases of
      adenocarcinoma, 16 cases of epidermoid and undifferentiated carcinoma, 8 cases of
      esthesioneuroblastoma, 5 cases of adenoid cystic carcinoma, 5 cases of melanoma,
      and 6 rare tumors. The stages (according to our new staging) were as follows: 37
      cases with T2, 27 cases with T3, and 27 cases with T4. The mean follow-up was 47
      months. Seven patients died after surgery (6 in the first series). The survival
      at 3 and 5 years was, respectively, 52% and 47%, and the disease-free survival
      (DFS) was 30% and 24%, with a statistically significant difference at
      multivariate analysis in favor of patients without prior treatment (p = .033) or
      T2 versus T3 and T4 (p<.007). CONCLUSIONS: An anterior craniofacial resection
      should be performed in cases of ethmoid tumors reaching or eroding the cribriform
      plate. A scrupulous intra- and postoperative approach is necessary to avoid
      severe complications. The patients often survive for a long time with recurrence
      ongoing. Our new staging identifies the critical extensions of ethmoid tumors.

PMID- 10208660
TI  - Evaluation of glycoprotein constituents in head and neck cancer patients
      undergoing radiotherapy.
AB  - BACKGROUND: Alterations in serum levels of several glycoprotein constituents are
      reported to be useful for treatment monitoring of cancer patients. The purpose of
      this study was to determine efficacy of sialic acid and seromucoid fraction as
      treatment monitors for head and neck (H&N) cancer patients undergoing
      radiotherapy (RT). METHODS: Serum levels of total sialic acid (TSA), lipid-bound
      sialic acid (LSA), and seromucoid fraction (measured as Mucoid protein [MP] and
      hexose) were studied in age matched controls and in patients with H&N cancer at
      diagnosis and during/after completion of RT. The markers were estimated by
      spectrophotometric methods. RESULTS: Serum levels of sialic acid forms and
      seromucoid fraction were significantly elevated (p<.001) in untreated H&N cancer
      patients (n = 32) as compared with controls (n = 50). The marker levels were
      significantly declined (p<.001) in H&N cancer patients who responded to RT as
      compared with their levels at diagnosis, whereas the levels were persistently
      elevated in nonresponders. CONCLUSION: Evaluation of sialic acid forms and
      seromucoid fraction could be used for monitoring the treatment of H&N cancer
      patients undergoing RT.

PMID- 10208661
TI  - Effect of clamp versus anastomotic-induced ischemia on critical ischemic time and
      survival of rat epigastric fasciocutaneous flap.
AB  - BACKGROUND: There are many models used to explore ischemic-related phenomena. The
      rat epigastric fasciocutaneous flap model is the one most commonly used. Critical
      ischemic time is the maximum ischemic insult that tissue can undergo and still
      remain viable. Experimentally, ischemia is induced either by clamping the
      vascular pedicle or by dividing the pedicle then performing microvascular
      arterial and venous anastomosis. We sought to determine what effect the different
      methods of inducing ischemia have on the critical primary ischemic time and,
      thus, flap survival. METHODS: A right 3 cm x 6 cm groin flap based on the
      inferior epigastric vessels was raised in each rat. Ischemic times of 4, 6, 8, or
      10 hours were induced either by placing temporary occlusion clamps on each vessel
      of the vascular pedicle (island pedicle group) or by ligation and division of the
      pedicle with subsequent microvascular anastomosis (free flap group). Survival was
      assessed at 7 days. RESULTS: The primary ischemic time at which one half of free
      flaps are predicted to die was calculated to be 7.60 hours, compared with 6.09
      hours for the island pedicle flaps (p<.05). CONCLUSIONS: Fasciocutaneous flaps
      undergoing ligation and anastomosis are more resistant to ischemia than are those
      undergoing clamping of the pedicle. Possible etiologic factors responsible for
      this experimental finding are discussed.

PMID- 10208662
TI  - Second neoplasm in patients with head and neck cancer.
AB  - BACKGROUND: The improvement in locoregional control of head and neck carcinomas
      over the last decades does not appear to modify the final survival of these
      patients, mainly due to the appearance of distant metastases and second
      neoplasms. We ran a study to evaluate the incidence of second neoplasms and their
      characteristics in patients with head and neck carcinoma treated in our hospital.
      METHODS: A retrospective study was undertaken to analyze the appearance of second
      neoplasm, its characteristics, and repercussion on the survival in 1845 patients
      with carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx diagnosed
      and treated in our department between 1984 and 1995. RESULTS: A group of 302
      patients (16%) developed a second neoplasm. The incidence of second neoplasms was
      4% per year and was constant during the follow-up period. Second neoplasms were
      mainly carcinomas located in head and neck (40%), lungs (31%), or esophagus (9%).
      Twenty percent of second neoplasms were tumors located outside the aerodigestive
      tract. The appearance of a second neoplasm significantly worsened the survival.
      CONCLUSIONS: Four percent per year of patients with carcinoma of the oral cavity,
      oropharynx, hypopharynx, and larynx develop a second neoplasm, most frequently a
      carcinoma of the aerodigestive tract. This leads to a significant worsening of
      survival.

PMID- 10208663
TI  - Percutaneous embolization to control intractable epistaxis in nasopharyngeal
      carcinoma.
AB  - BACKGROUND: Epistaxis in patients with nasopharyngeal carcinoma (NPC) who have
      received radiotherapy can be difficult to control by conventional methods. The
      use of angiography and embolization to control problematic epistaxis has been
      well documented in other situations, but its use in severe or recurrent epistaxis
      following irradiation for NPC has not been described. METHODS: We retrospectively
      reviewed case notes of all patients with NPC initially seen with epistaxis over a
      4-year period. Those patients with refractory epistaxis which could not be
      controlled by conventional methods and required angiography and embolization were
      assessed. RESULTS: Eight patients who underwent angiography were identified. Five
      patients showed hypervascularization and three patients had pseudoaneurysms or an
      aneurysm of the internal carotid artery seen on the angiogram. All these patients
      were successfully embolized. There were no significant complications after the
      procedure. CONCLUSION: We conclude that embolization is a safe and effective
      method of controlling refractory epistaxis in patients irradiated for NPC.

PMID- 10208664
TI  - A conservation approach to pharyngeal carcinoma with advanced neck disease:
      optimizing neck management.
AB  - BACKGROUND: Surgical management of advanced neck disease remains controversial
      when a conservative approach based on radiotherapy is retained for primary
      tumors. The objective of this study was to evaluate retrospectively treatment
      results in pharyngeal cancers presenting with N2-N3 neck disease, using neck
      dissection followed by radical locoregional radiotherapy (RT) and to compare
      these results with those obtained in patients treated by radical RT alone.
      METHODS: From August 1991 to November 1996, 41 patients with carcinomas of the
      oro- or hypopharynx were staged as T1-T3 N2-N3 M0 (American Joint Committee on
      Cancer [AJCC] stage IV). Twenty-four patients were treated with neck dissection
      followed by RT (group 1) and 17 patients with radical RT (group 2) using a
      progressively accelerated concomitant boost schedule. Chemotherapy was delivered
      to 6 patients in group 1 and 8 in group 2 partially concomitantly with RT.
      RESULTS: Three-year actuarial locoregional control was 73% and 55% for groups 1
      and 2, respectively (p = .52). The corresponding 3-year actuarial overall
      survival rates were 37% and 50% (p = .42). Severe postoperative complications
      were observed after neck dissection in four patients (16%). Acute toxicity during
      RT was similar in the two groups. Late toxicities were also similar, except for
      two patients in group 1 who developed severe laryngeal edema. CONCLUSIONS: Neck
      dissection followed by radical RT to the primary tumor and neck represents a
      valid treatment option in this subset of patients, allowing good control of
      advanced neck disease, while at the same time conserving pharyngolaryngeal
      function. However, for patients who are at high risk of severe postoperative
      complications, radical RT can be considered a worthy alternative, particularly
      for oropharyngeal carcinomas.

PMID- 10208665
TI  - Management of the neck after alternating chemoradiotherapy for advanced head and
      neck cancer.
AB  - BACKGROUND: To investigate neck control probability and the value of nodal
      response at completion of alternating chemoradiotherapy, a group of 43 patients
      was reviewed. METHODS: Patients were treated with 60 Gy alternated with four
      cycles of cisplatin and fluorouracil. All patients had lymph nodes positive for
      squamous cell carcinoma from various primary sites, underwent computed tomography
      (CT) for staging and evaluation of response, and were treated at a single
      institution. Patients with bilateral lymph nodes (N2c) were further staged
      according to the side of dominant neck disease. RESULTS: After chemoradiotherapy
      alone, 2-year neck control probabilities (NCP) are 86+/-13%, 58+/-10%, and 0 for
      N1, N2a/b, and N3 neck stages, respectively (p = .038). Two-year NCP for 25
      complete responders is 85+/-8%, whereas, at the same time interval, it is 17+/-9%
      for 18 partial responses (p<.0001). Within patients with N1-2a/b neck disease, 21
      complete responders had a 2-year NCP of 92+/-8%. Five (11%) heminecks in four
      patients developed severe (Radiation Therapy Oncology Group [RTOG] grade > 2)
      subcutaneous late reactions. CONCLUSIONS: For patients with N1-2a/b neck disease,
      response at the end of treatment as evaluated by both physical exam and CT is a
      reliable criterion to select patients for complementary surgery even after
      chemoradiotherapy. For N3 disease, planned neck dissection regardless of response
      seems warranted.

PMID- 10208666
TI  - Quality of life measurements of speech in the head and neck cancer patient
      population.
AB  - BACKGROUND: To employ patient-reported speech outcome data collected on head and
      neck cancer (HNC) surveys, there is a need to determine (1) the relationship of
      patient ratings to speech language pathologist (SLP) ratings and (2) whether
      patients' attitudes toward their speech are an important element of speech
      measurements. METHODS: Associations were analyzed between (1) patients' ratings
      of speech function on surveys and equivalent SLP ratings and (2) patients'
      ratings of speech function and their satisfaction with speech function. RESULTS:
      Patient-reported survey ratings were significantly associated with comparable SLP
      ratings. The associations were stronger for intelligibility than for voice
      quality. Patients' functional and attitudinal ratings were also significantly
      associated. The associations were relatively strong for composite speech items
      and intelligibility and moderate for voice quality. CONCLUSIONS: Patient-reported
      speech outcomes can be interpreted as being fairly equivalent to SLP evaluations.
      Attitudinal ratings appear to contribute an important aspect of the patients'
      perspective, with substantially different variances between function and
      attitude.

PMID- 10208667
TI  - Supraclavicular masses: results of a series of 309 cases biopsied by fine needle
      aspiration.
AB  - BACKGROUND: The purpose of this study was to determine the current distribution
      of diseases resulting in supraclavicular swelling or lymphadenopathy as diagnosed
      by fine needle aspiration (FNA) biopsy. METHODS: Supraclavicular aspirates in
      this retrospective 5-year study from a large public hospital were classified as
      neoplastic, infectious, inflammatory, reactive, and nondiagnostic. RESULTS:
      Malignancy was present in 55% of the 309 aspirates (47% metastatic, 8% lymphoma).
      Age was most predictive of malignancy (32% for age < or =41 years, 68% for age
      >40 years). Lymphoma occurred equally in both groups, but the lymphoma:metastasis
      ratio was much higher in younger patients (1:1.6 for age < or =41 years versus
      1:11 for age >40 years). Ethnic origin was related to tumor type, metastatic
      uterine cervical carcinoma being most frequent in Hispanics, and lymphoma in
      Caucasians. Primary oropharyngeal sites were unusual; most malignancies
      originated in the lung, breast, or cervix. Left or right side did not
      discriminate for either the presence or type of tumor. The 43 aspirates from
      human immunodeficiency virus (HIV) positive (+) patients were predominantly
      inflammatory, infectious, or reactive; lymphoma was infrequent (7%). Overall, 39
      patients had mycobacterial infection; aspirate smears or culture were positive in
      19. Three other FNAs grew Staphylococcus aureus and one stained for Cryptococcus.
      Aspirates were not informative in 24 cases (8%). The sensitivity of FNA for
      malignancy was 97%, specificity was 98%, and positive predictive value 98%.
      CONCLUSION: Aspiration biopsy is an excellent diagnostic tool for supraclavicular
      masses. Patients over 40 years old are likely to have metastatic malignancy, from
      breast, lung, or infradiaphragmatic sites. Aspirates with inflammation and those
      from HIV+ patients should undergo extensive culture.

PMID- 10208668
TI  - Non-Hodgkin's lymphoma of the head and neck: a 30-year experience at the
      University of Florida.
AB  - BACKGROUND: Outcome in previously untreated patients with non-Hodgkin's lymphoma
      of the head and neck needed to be assessed. METHODS: A retrospective review was
      performed of 79 patients with stage I or II non-Hodgkin's lymphoma of the head
      and neck treated between 1964 and 1994 with radiotherapy (RT) or combined
      modality therapy (CMT) at the University of Florida. Freedom from relapse, cause
      specific survival, and absolute survival were analyzed by the Kaplan-Meier
      method. Patterns of failure were defined, and the relationship between dose and
      infield recurrence was studied. Histology was classified as low grade or
      intermediate/high grade. RESULTS: At 10 years, absolute survival for patients
      with low-grade lymphoma treated with RT was 45%; absolute survival for patients
      with intermediate/high-grade lymphoma was 41% for those treated with RT and 57%
      for those who received CMT. Twenty-seven patients had a recurrence of lymphoma
      after initial treatment. Twenty patients (74%) had recurrences outside the
      radiation treatment field; 90% of these failures were in predictable sites that
      would be included in comprehensive lymphatic irradiation fields (Waldeyer's ring,
      mantle, and whole abdomen). No clear dose response was observed. Multivariate
      analysis showed that patients with tumors <5 cm in diameter had improved cause
      specific survival, absolute survival, and freedom from relapse compared with
      patients with tumors > or = 5 cm in diameter. CONCLUSIONS: Patients with non
      Hodgkin's lymphoma in the head and neck with tumors > or = 5 cm in diameter
      appear to have a worse prognosis than those with smaller tumors. The patterns of
      failure suggest that initial treatment with comprehensive lymphatic irradiation
      fields could potentially eliminate the majority of treatment failures.

PMID- 10208669
TI  - Neutron radiotherapy for the treatment of locally advanced major salivary gland
      tumors.
AB  - BACKGROUND: Malignant salivary gland tumors are rare tumors of the head and neck
      region. The treatment of these tumors has generally consisted of surgical
      extirpation, with postoperative radiotherapy improving locoregional control and
      survival in patients with high risk tumors. Neutron radiotherapy has been found
      to be more efficacious than conventional radiotherapy in the setting of
      inoperable or subtotally resected salivary gland tumors. METHODS: One hundred
      forty-eight patients with malignant salivary tumors of major salivary gland
      origin were treated at the University of Washington Medical Center with fast
      neutron radiotherapy between the years 1984 and 1995. One hundred twenty-eight
      patients were treated with curative intent, and of these, 120 patients had
      evidence of gross residual disease at the time of treatment. These patients
      constitute the main analysis of this paper. Of these patients, 19% had recurrent
      disease, 39% were initially seen with positive lymph nodes, and 11% had
      previously received full dose conventional radiotherapy. At the time of analysis,
      the median period at risk of survivors was 26 months. RESULTS: The 5-year
      actuarial locoregional control rate for all patients with gross tumor treated
      with curative intent was 59%. A tumor size < or =4 cm was associated with an
      excellent locoregional control rate (80%), and cause-specific survival (73%) at 5
      years compared with patients with larger tumors (35% and 22%, respectively,
      p<.001 in both cases). On univariate analysis, there appeared to be an advantage
      in locoregional control for patients with smaller sized tumors (< or =4 cm) who
      underwent an attempted surgical extirpation. Locoregional control was excellent
      (100%) in patients having a complete surgical resection of their tumors and
      undergoing postoperative neutron radiotherapy because of the presence of other
      high risk factors. Lymph node status at the time of treatment, base of skull
      involvement, and male sex were associated with the development of distant
      metastasis, with 52% of node positive patients developing distant metastases by 5
      years, compared with 32% of node negative patients (p = .04). CONCLUSIONS:
      Neutron radiotherapy is an effective form of treatment for patients with high
      risk, locally advanced tumors of major salivary gland origin. An initial surgical
      resection appears beneficial in patients for whom such an approach is feasible.

PMID- 10208670
TI  - Atypical presentations of actinomycosis.
AB  - BACKGROUND: Actinomycotic infections of the cervicofacial region are uncommon.
      Most major medical centers report approximately one case per year. Presenting
      clinical manifestations are confusing because they often mimic other disease
      processes. Diagnosis may be difficult due to a general lack of familiarity with
      the disease and the fastidious nature of the organism in culture. The
      cervicofacial manifestations of actinomycosis are varied, and a high index of
      suspicion is required to make an accurate and timely diagnosis. METHODS:
      Retrospective chart review with the presentation of four unusual cases of
      actinomycosis were performed. RESULTS: Two patients were initially seen with
      dysphagia from a tongue base mass. The third patient was initially seen with a 3
      week history of worsening hoarseness and stridor. Examination revealed an
      ulcerative lesion of the left hemilarynx and pyriform sinus. All three patients
      were thought to have a neoplastic process. Diagnosis was made on histologic
      examination of a tissue biopsy. The fourth patient was initially seen with a
      buccal space mass that was draining externally. Culture of the purulent drainage
      revealed Actinomyces. In all four cases, symptoms resolved after appropriate
      antimicrobial therapy. CONCLUSIONS: Actinomycosis of the head and neck, although
      rare, is an important entity to the otolaryngologist. A confusing clinical
      presentation combined with the fastidious nature of the organism make for a
      difficult diagnosis. A high index of suspicion is required to make an accurate
      diagnosis and institute the appropriate antibiotic therapy.

PMID- 10208671
TI  - Axillary nodal metastases in head and neck cancer.
AB  - BACKGROUND: Axillary node metastasis is an uncommon occurrence in squamous
      carcinoma of the upper aerodigestive tract. METHODS: The tumor registry of The
      Johns Hopkins University Department of Otolaryngology-Head and Neck Surgery
      contained four cases of metastasis to the axilla from head and neck primary
      sites. A retrospective review of these cases was performed. RESULTS: Each patient
      had been initially treated for cancer years earlier including surgery and
      radiation to the neck. A recurrent cancer or a new primary then developed in the
      upper aerodigestive tract prior to the development of the axillary metastases.
      CONCLUSIONS: The common course of disease in these patients suggests that
      alteration of the lymphatic anatomy by previous treatment may have caused a new
      pattern of metastatic spread upon reseeding from the mucosa, resulting in the
      axillary metastases. Routine surveillance of the axillae by physical examination
      and/or computerized imaging in at risk patients may permit the early diagnosis of
      axillary metastases.

PMID- 10208672
TI  - Dendritic cell sarcoma of the thyroid.
AB  - BACKGROUND: Follicular dendritic cell sarcoma (FDCS) arises from nonlymphatic
      antigen-presenting cells found in lymph node B-cell follicles. This extremely
      rare tumor, which usually arises in lymph nodes, does occur in extranodal head
      and neck sites such as the tonsil and soft palate. METHODS: A retrospective
      review of the patient followed at the University of Pittsburgh Medical Center
      from 1993 to the present was performed. CONCLUSIONS: This is the first reported
      case of an FDCS of the thyroid. A review of the literature provides useful
      information to aid in detection, treatment, and outcome of this unusual soft
      tissue malignancy.

PMID- 10208673
TI  - Facial nerve reconstruction and facial reanimation following oncologic surgery.

PMID- 10208674
TI  - Is routine follow-up useful after combined-modality therapy for advanced head and
      neck cancer?
AB  - OBJECTIVE: To evaluate the usefulness of routine follow-up in a selected group of
      patients with head and neck cancer. DESIGN: Retrospective cohort study with
      follow-up of 5 years for all patients. PATIENTS: Three hundred two patients with
      advanced (stage II or IV) squamous cell carcinoma of the oral cavity, oropharynx,
      hypopharynx, and larynx were treated with curative intent with surgery and
      postoperative radiation therapy between January 1, 1970, and December 31, 1990.
      MAIN OUTCOME MEASURE: Survival after recurrence of the index tumor or the
      development of a second head and neck primary tumor. RESULTS: Overall actuarial 5
      year survival was 56%. Relapse occurred in 119 patients, and salvage therapy was
      attempted in 49 patients. Only 2 patients survived to 5 years after relapse.
      CONCLUSION: In patients with advanced head and neck squamous cell carcinoma,
      routine follow-up is more important for evaluation of treatment results and
      emotional support than of benefit in improving patient survival.

PMID- 10208675
TI  - Integrating radiological criteria into the classification of cervical lymph node
      disease.

PMID- 10208676
TI  - An imaging-based classification for the cervical nodes designed as an adjunct to
      recent clinically based nodal classifications.
AB  - Over the past 18 years, numerous classifications have been proposed to
      distinguish among the diverse nodal levels. Some classifications have used
      surgical landmarks, others physical assessment criteria. These classifications do
      not agree precisely and exhibit sufficient variation that competent physicians
      could arrive at slightly different staging of the patient's nodal disease. In the
      past 2 decades, computed tomography and magnetic resonance imaging have offered
      progressively more refined anatomical precision, reproducibility, and
      visualization of deep, clinically inaccessible structures. Because the majority
      of patients with head and neck malignancies presently undergo sectional imaging
      prior to treatment planning, we felt a need to integrate anatomical imaging
      criteria with the 2 most commonly used nodal classifications: those of the
      American Joint Committee on Cancer and those of the American Academy of
      Otolaryngology-Head and Neck Surgery. The imaging-based nodal classification
      proposed herein has been developed in consultation with surgeons interested in
      such classifications in the hope that the resultant classification would find
      ready acceptance by both clinicians and imagers. It is our desire that the best
      attributes of imaging, combined with those of the physical assessment, can result
      in a better and more consistently reproducible nodal staging than is possible by
      either

PMID- 10208677
TI  - Complications from planned, posttreatment neck dissections.
AB  - OBJECTIVE: To report the complication rate from planned, posttreatment neck
      dissections in patients who show control of primary squamous cell carcinoma by
      chemotherapy and radiotherapy or radiotherapy alone. DESIGN: Retrospective review
      of case series. SETTING: Georgetown University Medical Center, Washington, DC.
      PATIENTS: Thirty-four patients with clinically positive neck disease treated with
      organ preservation therapy for squamous cell carcinoma of the head and neck.
      INTERVENTIONS: Planned neck dissection after treatment with chemotherapy and
      radiotherapy or radiotherapy alone. MAIN OUTCOME MEASURE: Perioperative
      complications. RESULTS: Forty-one neck dissections were performed on 34 patients.
      Complications were seen in 13 (38%) of 34 patients and 15 (37%) of 41 neck
      dissections. Wound complications occurred in 9 (22%) of 41 dissections. Neck
      dissection complication rate did not correlate with previous use of chemotherapy
      or with the use of brachytherapy at the primary site at the time of the neck
      dissection. Preoperative radiotherapy dose greater than 70 Gy was associated with
      complications in 58% vs 29% when preoperative dose was less than 70 Gy (P = .09).
      This trend was reflected primarily in wound complications (42% vs 14%; P = . 10)
      and reached significance for skin flap necrosis (33% vs 0%; P = .005). Other
      factors that were associated with increased complications were preoperative
      albumin level less than 38 g/L and early neck drain removal. CONCLUSIONS: The
      complication rate associated with planned posttreatment neck dissection is
      similar to that previously reported for neck dissection. Wound complications are
      more common when higher preoperative radiotherapy doses are used.

PMID- 10208678
TI  - Pharyngeal transport dysfunction consequent to an organ-sparing protocol.
AB  - OBJECTIVE: To investigate the effects of a protocol of concomitant intravenous
      hydroxyurea and hyperfractionated, accelerated, external-beam radiation therapy
      on the swallowing mechanism of patients with advanced-stage head and neck cancer.
      DESIGN: Posttreatment videofluoroscopic swallow function studies, using images of
      single-bolus swallows of low-density liquid barium, were analyzed in real time,
      slow motion, and frame by frame using an integrated system that allows objective
      analysis of video recordings through image processing and digitization (Kay
      Elemetrics Computerized Swallowing Station). Radiological descriptors were used
      for pharyngeal transport abnormalities, and temporal measures were obtained of
      structural movements. SETTING: Academic, tertiary care, referral medical center.
      PATIENTS: Fifteen consecutive patients with previously untreated, stages III and
      IV, nonmetastatic squamous cell carcinoma of the head and neck who underwent a
      phase 1 study of prolonged infusion hydroxyurea therapy in combination with
      hyperfractionated, accelerated external-beam radiation therapy for their disease.
      RESULTS: All patients had anterior pharyngeal segment dysfunction, characterized
      by no epiglottic movement and slowed laryngeal motility (1.011 +/- 0.379 seconds
      [mean +/- SD). Anterior pharyngeal dysfunction was more severe in patients with
      primary tumors of the hypopharynx than in those with cancer of the oropharynx.
      Twelve (80%) of our patients demonstrated posterior pharyngeal segment
      dysfunction characterized by impaired pharyngeal constrictor motility. All 15
      patients displayed pharyngeal stage abnormalities that limited bolus transport
      and clearance. CONCLUSIONS: Severe pharyngeal physiological abnormalities were
      present that led to impaired bolus transport and that were frequent and
      debilitating consequences of this organ-sparing protocol. Long-term follow-up of
      this group will be required to assess the permanence of the abnormalities.

PMID- 10208679
TI  - Spontaneous apoptosis and the expression of p53 and Bcl-2 family proteins in
      locally advanced head and neck cancer.
AB  - BACKGROUND: Apoptotic cell death plays a key role in the pathogenesis,
      aggressiveness, and therapy responsiveness of cancer. The suicidal machinery of
      apoptosis is genetically controlled. Proteins of the Bcl-2 family as well as p53
      are important regulators of apoptosis. OBJECTIVE: To assess the rate of
      spontaneous apoptosis and the expression of p53 and Bcl-2 family proteins in
      locally advanced squamous cell carcinomas of the head and neck. DESIGN: Twenty
      six patients with locally advanced squamous cell carcinoma of the head and neck
      were included in the study. The expression of p53, Bcl-2, Mcl-1, Bax, and Bak was
      assessed by immunohistochemical analysis. The terminal deoxytransferase-mediated
      deoxyuridine nick end-labeling assay was used to quantify apoptosis by flow
      cytometry. RESULTS: Tumor cells containing immunostaining for the antiapoptotic
      proteins Bcl-2 and Mcl-1 were present in 4 (15%) and 24 (92%) of the cases
      evaluated, respectively, whereas immunopositivity for the proapoptotic proteins
      Bax and Bak was found in 9 (35%) and 24 (92%) of the samples. Immunoreactivity to
      p53 was detected in 20 (77%) of the samples. There was a positive correlation
      between the expression of Bcl-2 and Bax and between Mcl-1 and Bak. A low fraction
      of apoptotic cells (<2.5%) in the pretreatment tumor samples was significantly
      correlated with increased 2-year survival in these patients. CONCLUSIONS: Our
      results establish the frequent expression of the Bcl-2 family proteins Bcl-2, Mcl
      1, Bax, and Bak in locally advanced head and neck cancer. In addition, this study
      suggests that the apoptotic fraction in pretreatment tumor samples might be of
      prognostic importance for the outcome in these patients.

PMID- 10208680
TI  - Effects of stromal fibroblasts and fat cells and an environmental factor air
      exposure on invasion of laryngeal carcinoma (HEp-2) cells in a collagen gel
      invasion assay system.
AB  - OBJECTIVE: To clarify the invasion mechanism of laryngeal carcinoma (HEp-2)
      cells. DESIGN: Human HEp-2 cells were cultured on a collagen gel containing
      fibroblasts and/or fat cells. The HEp-2 cells were also treated with air exposure
      as the local environment of the laryngeal epithelial mucosa. A collagen gel
      invasion assay was conducted under these culture conditions. RESULTS: No invasion
      of HEp-2 cells was found in the stromal cell-free collagen gel, but a slight
      invasion was observed in the fibroblast-embedded gel. A deeper invasion of HEp-2
      cells occurred in the fibroblast- and fat cell-coembedded gel and in the
      fibroblast-embedded gel with air exposure. The most extensive invasion of HEp-2
      cells was observed under the fibroblast- and fat cell-coembedded gel in
      combination with air exposure. CONCLUSIONS: Fat cells and air exposure clearly
      increase the invasive effect of fibroblasts in squamous cell carcinoma of the
      larynx. The combined effect of these 3 factors (ie, fat cells, fibroblasts, and
      air exposure) plays a very important role in the invasive growth of the carcinoma
      cells. This observation suggests that both tumor cell-stromal cell interaction
      and tumor cell-local environmental factor interaction should be taken into
      account in an investigation of the invasive and proliferative mechanisms of
      laryngeal carcinoma.

PMID- 10208681
TI  - Two-port endoscopy of the middle ear: endoscopic anatomy.
AB  - OBJECTIVES: To shed light on the endoscopic anatomy of the middle ear seen on 2
      port endoscopy and to describe potential clinical applications. DESIGN:
      Anatomical structures were visualized by transmeatal or transtympanic rigid
      scopes of different angles and by a flexible scope in the eustachian tube. This
      arrangement ensured reciprocal guidance of the scopes and provided access to
      regions not seen otherwise. SETTING: The Department of Anatomy 1, University of
      Vienna, Vienna, Austria. MATERIALS: Forty tympanic cavities obtained from cadaver
      skulls without prior fixation were examined. Specimens did not show any
      abnormalities and were chosen without regard to age or sex. RESULTS: Depending on
      the angle of view, rigid transmeatal or transtympanic endoscopes provided a full
      view of the entire tympanic cavity except for the epitympanum, access to which
      was barred by the incudomallear joint, the mallear folds, and the tympanic chord,
      but the epitympanum was well visualized through the flexible, steerable,
      transtubal scope. CONCLUSIONS: Two-port endoscopy of the middle ear offers a full
      view of all structures in the tympanic cavity. The atraumatic transtubal approach
      to the tympanic cavity enhances the safety of transmeatal interventions and
      facilitates postoperative follow-up.

PMID- 10208682
TI  - Hearing impairment related to age in Usher syndrome types 1B and 2A.
AB  - OBJECTIVE: To evaluate hearing impairment in 2 common genetic subtypes of Usher
      syndrome, USH1B and USH2A. DESIGN: Cross-sectional analysis of hearing threshold
      related to age in patients with genotypes determined by linkage and mutation
      analysis. SETTING: Otolaryngology department, university referral center.
      PATIENTS: Nineteen patients with USH1B and 27 with USH2A were examined. All
      participants were living in the Netherlands and Belgium. MAIN OUTCOME MEASURE:
      Pure tone audiometry of the best ear at last visit. RESULTS: The patients with
      USH1B had residual hearing without age dependence, with minimum thresholds of 80,
      95, and 120 dB at 0.25, 0.5, and 1 to 2 kHz, respectively. Mean thresholds of
      patients with USH2A were about 45 to 55 dB better than these minimum values.
      Distinctive audiographic features of patients with USH2A were maximum hearing
      thresholds of 70, 80, and 100 dB at 0.25, 0.5, and 1 kHz, respectively, only at
      younger than 40 years. Progression of hearing impairment in USH2A was 0.7 dB/y on
      average for 0.25 to 4 kHz and could not be explained by presbyacusis alone.
      CONCLUSIONS: The USH1B and USH2A can be easily distinguished by hearing
      impairment at younger than 40 years at the low frequencies. Hearing impairment in
      our patients with USH2A could be characterized as progressive.

PMID- 10208683
TI  - Otorrhea after insertion of silver oxide-impregnated silastic tympanostomy tubes.
AB  - BACKGROUND: Silver oxide-impregnated tympanostomy tubes have been shown to
      decrease the incidence of postoperative otorrhea, but without a significant
      effect in the first postoperative week. OBJECTIVE: To evaluate prospectively our
      results with silver oxide-impregnated tympanostomy tubes and to identify factors
      associated with a higher incidence of early postoperative otorrhea. DESIGN:
      Prospective nonrandomized study. SETTING: University referral center. PATIENTS
      AND OTHER PARTICIPANTS: Six hundred thirty patients with chronic otitis media
      with effusion or recurrent otitis media. INTERVENTIONS: Silver oxide-impregnated
      Silastic tympanostomy tubes were inserted in 1254 ears. Subjects with mucoid or
      purulent effusions or blood at the myringotomy site at surgery were treated with
      topical antibiotic prophylaxis (sulfacetamide sodium-prednisolone acetate or
      neomycin sulfate-polymyxin B sulfate-hydrocortisone) for 5 days after
      tympanostomy tube placement. MAIN OUTCOME MEASURES: Incidence of otorrhea after
      tympanostomy tube insertion at 1 week and 1, 3, 6, 9, and 12 months after
      surgery. RESULTS: The overall incidence of postoperative otorrhea was 1.9%. The
      incidence of otorrhea in the first postoperative week was 5.6%; the incidence of
      otorrhea after the first postoperative week was 1.2% (P<.001). Within the first
      postoperative week, a significantly greater incidence of otorrhea was noted in
      patients younger than 3 years (7.8%), in patients with mucoid effusions at
      surgery (8.6%), and in patients younger than 3 years with mucoid effusions at
      surgery (15.2%). CONCLUSIONS: Silver oxide-impregnated tympanostomy tubes are
      associated with a low overall incidence of postoperative otorrhea. A
      significantly higher incidence of otorrhea is seen during the first postoperative
      week, compared with the incidence after the first week. Patients with thick
      middle ear effusions and age younger than 3 years have a significantly greater
      incidence of early otorrhea after tympanostomy tube placement.

PMID- 10208684
TI  - Insulinlike growth factor 1- and 2-augmented collagen gel repair of facial
      osseous defects.
AB  - BACKGROUND: Defects of the facial bone structure are common problems for the
      facial plastic surgeon. Native type 1 collagen gels (T1CGs) have been shown to
      mediate repair of facial critical-size defects in rat models. OBJECTIVE: To
      evaluate the efficacy of T1CG augmented with insulinlike growth factor (IGF) 1,
      IGF-2, and a combination of IGF-1 and IGF-2 on the repair of facial critical-size
      defects in a rodent model. METHODS: Twenty-four retired male breeder Sprague
      Dawley rats were divided into 4 groups of 6 animals. Facial critical-size defects
      were created by removing the nasalis bones with a bone-cutting drill. Defects
      were treated with 300 pg of type 1 collagen gel (T1CG), T1CG augmented with 3
      microg of IGF-1, T1CG augmented with 3 microg of IGF-2, or T1CG augmented with a
      combination of 3 microg of IGF-1 and 3 microg of IGF-2. After 30 days the animals
      were examined at necropsy with precise planimetry, histological analysis of new
      bone growth, and radiodensitometric analysis of bone thickness. RESULTS:
      Radiodensitometric measurements showed that IGF-2 augmentation resulted in
      greatest osseous healing, with measurements being statistically significant over
      those of all other groups (P< or = .03). Combination IGF-1 and IGF-2 had osseous
      healing that was intermediate between IGF-1 augmentation and IGF-2 augmentation
      alone, with measurements being statistically significant over those of
      unaugmented gels (P<.001) and IGF-1 augmentation (P< or = .03). Augmentation with
      IGF-1 resulted in healing that was significant over that of unaugmented gels (P<
      or = .04). CONCLUSION: Collagen gels augmented with IGF significantly enhance the
      osteoconductive repair of nasal critical-size defects in a rodent model, with IGF
      2 showing highest efficacy.

PMID- 10208685
TI  - Expanded polytetrafluoroethylene (Gore-Tex) augmentation of deep nasolabial
      creases.
AB  - OBJECTIVE: To evaluate the safety and efficacy of expanded
      polytetrafluoroethylene (PTFE) (Gore-Tex; W. L. Gore & Associates, Flagstaff,
      Ariz) for augmentation of deep nasolabial creases. DESIGN: Retrospective chart
      review with a minimum of 12 months of follow-up. SETTING: Private practice
      ambulatory surgery center. STUDY POPULATION: One hundred consecutive patients
      (average age, 49 years) undergoing expanded PTFE augmentation of the nasolabial
      crease. MAIN OUTCOME MEASURES: A standardized, reproducible rating scale assessed
      preoperative crease severity. Clinical effectiveness was determined by the
      numerical degree of improvement in crease severity rating after surgery, and by
      the number of procedures required to achieve the desired aesthetic results.
      RESULTS: Patients initially had grade 1 (14.5%), grade 2 (54.0%), grade 3
      (20.0%), or grade 4 (11.5%) crease severity ratings. On average, patients with
      grade 1 creases required 1.17 total augmentation procedures, those with grade 2
      required 1.60, those with grade 3 required 1.93, and those with grade 4 required
      1.86. On average, with each augmentation, patients with grade 1 improved 0.61
      relative severity points; those with grade 2, 0.85; those with grade 3, 1.29; and
      those with grade 4, 1.28. Nine patients developed late postoperative sequelae.
      Four creases (2.0%) displayed an unnatural mounded appearance because of
      superficial expanded PTFE placement. All 4 creases underwent elective removal of
      a single superficial PTFE strip, with resultant return of aesthetically correct
      crease augmentation. Five creases (2.5%) developed implant site infections; in
      all 5 cases, the involved strips were removed and the infection was resolved with
      a 10-day course of oral antibiotics. CONCLUSIONS: Expanded PTFE augmentation
      presents a safe, effective method for softening deep nasolabial creases. Patients
      with more severe creases are likely to show more improvement with each
      augmentation, but are also more likely to require multiple procedures to achieve
      the desired aesthetic result.

PMID- 10208686
TI  - Pathologic quiz case 1. Laryngeal saccular cyst.

PMID- 10208687
TI  - Pathologic quiz case 2. Soft tissue myxoma of the parotid gland.

PMID- 10208688
TI  - Is E-mail an effective medium for physician-patient interactions?

PMID- 10208689
TI  - E-mail: effective if handled with care.

PMID- 10208691
TI  - Candy building blocks: an aspiration risk.

PMID- 10208690
TI  - Brave new world.

PMID- 10208692
TI  - Functional results after oropharyngeal reconstruction: a different perspective.

PMID- 10208693
TI  - A few issues about the bionic ear.

PMID- 10208694
TI  - Imaging plane angulation and partial volume.

PMID- 10208695
TI  - Otic rosacea.

PMID- 10208696
TI  - Contaminated toothbrushes and pharyngitis.

PMID- 10208697
TI  - Preventive care for the elderly: getting by in the absence of evidence.

PMID- 10208698
TI  - Prevention of relapse in alcohol dependence.

PMID- 10208699
TI  - Management of gastroenteritis in breast-fed children.

PMID- 10208700
TI  - Diagnosis and management of gout.
AB  - Gout is a disease resulting from the deposition of urate crystals caused by the
      overproduction or underexcretion of uric acid. The disease is often, but not
      always, associated with elevated serum uric acid levels. Clinical manifestations
      include acute and chronic arthritis, tophi, interstitial renal disease and uric
      acid nephrolithiasis. The diagnosis is based on the identification of uric acid
      crystals in joints, tissues or body fluids. Treatment goals include termination
      of the acute attack, prevention of recurrent attacks and prevention of
      complications associated with the deposition of urate crystals in tissues.
      Pharmacologic management remains the mainstay of treatment. Acute attacks may be
      terminated with the use of nonsteroidal anti-inflammatory agents, colchicine or
      intra-articular injections of corticosteroids. Probenecid, sulfinpyrazone and
      allopurinol can be used to prevent recurrent attacks. Obesity, alcohol intake and
      certain foods and medications can contribute to hyperuricemia. These potentially
      exacerbating factors should be identified and modified.

PMID- 10208701
TI  - Safety of radiographic imaging during pregnancy.
AB  - Maternal illness during pregnancy is not uncommon and sometimes requires
      radiographic imaging for proper diagnosis and treatment. The patient and her
      physician may be concerned about potential harm to the fetus from radiation
      exposure. In reality, however, the risks to the developing fetus are quite small.
      The accepted cumulative dose of ionizing radiation during pregnancy is 5 rad, and
      no single diagnostic study exceeds this maximum. For example, the amount of
      exposure to the fetus from a two-view chest x-ray of the mother is only 0.00007
      rad. The most sensitive time period for central nervous system teratogenesis is
      between 10 and 17 weeks of gestation. Nonurgent radiologic testing should be
      avoided during this time. Rare consequences of prenatal radiation exposure
      include a slight increase in the incidence of childhood leukemia and, possibly, a
      very small change in the frequency of genetic mutations. Such exposure is not an
      indication for pregnancy termination. Appropriate counseling of patients before
      radiologic studies are performed is critical.

PMID- 10208702
TI  - Chronic abdominal pain in childhood: diagnosis and management.
AB  - More than one third of children complain of abdominal pain lasting two weeks or
      longer. The diagnostic approach to abdominal pain in children relies heavily on
      the history provided by the parent and child to direct a step-wise approach to
      investigation. If the history and physical examination suggest functional
      abdominal pain, constipation or peptic disease, the response to an empiric course
      of medical management is of greater value than multiple "exclusionary"
      investigations. A symptom diary allows the child to play an active role in the
      diagnostic process. The medical management of constipation, peptic disease and
      inflammatory bowel disease involves nutritional strategies, pharmacologic
      intervention and behavior and psychologic support.

PMID- 10208704
TI  - Adhesive capsulitis: a sticky issue.
AB  - The shoulder is a very complex joint that is crucial to many activities of daily
      living. Decreased shoulder mobility is a serious clinical finding. A global
      decrease in shoulder range of motion is called adhesive capsulitis, referring to
      the actual adherence of the shoulder capsule to the humeral head. Adhesive
      capsulitis is a syndrome defined as idiopathic restriction of shoulder movement
      that is usually painful at onset. Secondary causes include alteration of the
      supporting structures of and around the shoulder, and autoimmune, endocrine or
      other systemic diseases. The three defined stages of this condition are the
      painful stage, the adhesive stage and the recovery stage. Although recovery is
      usually spontaneous, treatment with intra-articular corticosteroids and gentle
      but persistent physical therapy may provide a better outcome, resulting in little
      functional compromise.

PMID- 10208703
TI  - Health screening in older women.
AB  - Health screening is an important aspect of health promotion and disease
      prevention in women over 65 years of age. Screening efforts should address
      conditions that cause significant morbidity and mortality in this age group. In
      addition to screening for cardiovascular disease, cerebrovascular disease and
      cancer, primary care physicians should identify risk factors unique to an aging
      population. These factors include hearing and vision loss, dysmobility or
      functional impairment, osteoporosis, cognitive and affective disorders, urinary
      incontinence and domestic violence. Although screening for many conditions cannot
      be proved to merit an "A" recommendation (indicating conclusive proof of
      benefit), special attention to these factors can decrease morbidity and improve
      quality of life in aging women.

PMID- 10208705
TI  - Caring for infants with congenital heart disease and their families.
AB  - Congenital heart defects are classified into two broad categories: acyanotic and
      cyanotic lesions. The most common acyanotic lesions are ventricular septal
      defect, atrial septal defect, atrioventricular canal, pulmonary stenosis, patent
      ductus arteriosus, aortic stenosis and coarctation of the aorta. Congestive heart
      failure is the primary concern in infants with acyanotic lesions. The most common
      cyanotic lesions are tetralogy of Fallot and transposition of the great arteries.
      In infants with cyanotic lesions, hypoxia is more of a problem than congestive
      heart failure. Suspicion of a congenital heart defect should be raised by the
      presence of feeding difficulties in association with tachypnea, sweating and
      subcostal recession, or severe growth impairment. Follow-up of infants with
      congenital heart disease should follow the schedule of routine care for healthy
      babies with some modifications, such as administration of influenza and
      pneumococcal vaccines. More frequent follow-up is required if congestive heart
      failure is present. Family psychosocial issues should also be addressed. One of
      the main roles for the family physician is to help the parents put the diagnosis
      in perspective by clarifying expectations and misconceptions, and answering
      specific questions.

PMID- 10208706
TI  - Topical therapies for glaucoma: what family physicians need to know.
AB  - Medication classes historically used in the management of glaucoma include beta
      blockers, miotics, sympathomimetics and carbonic anhydrase inhibitors. Because
      topically applied medications are more site specific, they are preferred in the
      treatment of glaucoma. Compared with oral medications, topical agents are
      associated with a decreased incidence of systemic side effects. With topical
      administration, conjunctival and localized skin allergic reactions are relatively
      common, whereas severe reactions, including death, are rare. Recently introduced
      topical agents for glaucoma therapy include dorzolamide and brinzolamide, the
      first topical carbonic anhydrase inhibitors; brimonidine and apraclonidine, more
      ocular-specific alpha agonists; and latanoprost, a prostaglandin analog, which is
      a new class of glaucoma medication. Latanoprost has the unique side effect of
      increasing iris pigmentation. Like their predecessors, the newer agents lower
      intraocular pressure by a statistically significant degree. Preservation of
      visual field, the more substantial patient-oriented end point, continues to be
      studied.

PMID- 10208707
TI  - Multiple myeloma: recognition and management.
AB  - Multiple myeloma is the malignant proliferation of plasma cells involving more
      than 10 percent of the bone marrow. The multiple myeloma cell produces monoclonal
      immunoglobulins that may be identified on serum or urine protein electrophoresis.
      Bone pain related to multiple lytic lesions is the most common clinical
      presentation. However, up to 30 percent of patients are diagnosed incidentally
      while being evaluated for unrelated problems, and one third of patients are
      diagnosed after a pathologic fracture, commonly of the axial skeleton. Multiple
      myeloma must be differentiated from other causes of monoclonal gammopathy,
      including monoclonal gammopathy of undetermined significance, heavy chain
      disease, plasmacytoma and Waldenstrom macroglobulinemia. Chemotherapy with
      melphalan-prednisone is the standard treatment for multiple myeloma. Other
      treatment modalities include polychemotherapy and bone marrow transplantation.
      Only 50 to 60 percent of patients respond to therapy. The aggregate median
      survival for all stages of multiple myeloma is three years.

PMID- 10208708
TI  - Chronic critical limb ischemia: diagnosis, treatment and prognosis.
AB  - Chronic critical limb ischemia is manifested by pain at rest, nonhealing wounds
      and gangrene. Ischemic rest pain is typically described as a burning pain in the
      arch or distal foot that occurs while the patient is recumbent but is relieved
      when the patient returns to a position in which the feet are dependent. Objective
      hemodynamic parameters that support the diagnosis of critical limb ischemia
      include an ankle-brachial index of 0.4 or less, an ankle systolic pressure of 50
      mm Hg or less, or a toe systolic pressure of 30 mm Hg or less. Intervention may
      include conservative therapy, revascularization or amputation. Progressive
      gangrene, rapidly enlarging wounds or continuous ischemic rest pain can signify a
      threat to the limb and suggest the need for revascularization in patients without
      prohibitive operative risks. Bypass grafts are usually required because of the
      multilevel and distal nature of the arterial narrowing in critical limb ischemia.
      Patients with diabetes are more likely than other patients to have distal disease
      that is less amenable to bypass grafting. Compared with amputation,
      revascularization is more cost-effective and is associated with better
      perioperative morbidity and mortality. Limb preservation should be the goal in
      most patients with critical limb ischemia.

PMID- 10208709
TI  - Insomnia.
AB  - Insomnia is a common complaint with potentially significant medical and
      psychologic complications. In some cases insomnia presents as a symptom of
      another underlying medical, psychiatric or environmental condition. In these
      cases, management of insomnia depends on accurate diagnosis and successful
      treatment of the underlying condition. In other cases, insomnia is a primary
      disorder requiring direct treatment. Pharmacologic treatments include
      nonprescription medications, sedating tricyclic antidepressants, benzodiazepines
      and related drugs. Behavior management methods that may be administered in the
      office setting include stimulus control therapy, sleep restriction therapy and
      sleep hygiene education. Although prescription medications and behavior therapy
      have similar short-term efficacy, behavior interventions are recommended as the
      first line of treatment for primary insomnia because of their greater safety and
      long-term efficacy.

PMID- 10208710
TI  - Photo quiz. A pelvic mass.

PMID- 10208712
TI  - Dealing with your own parent's illness.

PMID- 10208713
TI  - CDC issues revised guidelines for the prevention of human rabies.

PMID- 10208714
TI  - AAP updates its guidelines for evaluation of sexual abuse. American Academy of
      Pediatrics.

PMID- 10208715
TI  - AAP policy on children with HIV-infected parents. American Academy of Pediatrics.

PMID- 10208716
TI  - Fulfilling a social contract: alliance of health professional students.

PMID- 10208717
TI  - Orientation in pied flycatchers: the relative importance of magnetic and visual
      information at dusk.
AB  - We investigated the orientation of juvenile pied flycatchers, Ficedula hypoleuca,
      during autumn migration in south Sweden using orientation cage experiments, to
      study the relative importance of visual and magnetic information at sunset. We
      performed cage tests under 12 experimental conditions that manipulated the
      geomagnetic and visual sunset cues available for orientation: natural clear skies
      in the local or a vertical magnetic field; simulated total overcast in the local
      or a vertical magnetic field; natural pattern of skylight polarization and
      directional information from stars screened off, with the sun's position as
      normal or shifted 120 degrees anticlockwise with mirrors; reduced polarization in
      the local or a vertical magnetic field; directions of polarization (e-vector)
      NE/SW and NW/SE, respectively, in the local or a vertical magnetic field. The
      pied flycatchers were significantly oriented towards slightly south of west when
      they could use a combination of skylight and geomagnetic cues. The mean
      orientation was significantly shifted along with the deflection of the sunset
      position by mirrors. Reduced polarization had no significant effect on
      orientation either in the local, or in a vertical, magnetic field. The birds
      tended to orient parallel with the axis of polarization, but only when the
      artificial e-vector was aligned NW/SE. The mean orientation under simulated total
      overcast in a vertical, and in the local, magnetic field was not significantly
      different from random. It is difficult to rank either cue as dominant over the
      other and we conclude that both visual and magnetic cues seem to be important for
      the birds' orientation when caught and tested during active migration. Copyright
      1999 The Association for the Study of Animal Behaviour.

PMID- 10208719
TI  - Editor's note 

PMID- 10208720
TI  - WHO requirements for the use of animal cells as in vitro substrates for the
      production of biologicals (Requirements for biological susbstances no. 50).

PMID- 10208721
TI  - WHO guidelines for the production and control of the acellular pertussis
      component of monovalent or combined vaccines.

PMID- 10208722
TI  - WHO guidelines for assuring the quality of DNA vaccines.

PMID- 10208723
TI  - Single radial immunodiffusion as a method for the assay of the acellular
      pertussis vaccine components, pertussis toxoid, filamentous haemagglutinin and
      pertactin.
AB  - The development of acellular pertussis vaccines has raised a number of issues
      relevant to the control of these products. Of particular importance is the need
      for robust and accurate in vitro assays for the antigen content of the vaccines
      which might contain up to five different antigen components, each of which needs
      to be independently assayed. This paper describes a simple method for the
      quantification of three component antigens. Because relatively high doses of
      purified antigens are used in those preparations, the elimination of residual
      toxicity is a major concern. This is achieved by genetic modification of chemical
      treatment. The latter results in modification of the immunological reactivity of
      the antigens making direct assay by such methods as ELISA ineffective. A single
      radial diffusion technique using polyclonal antisera for the assay of pertussis
      toxoid (PTxd), chemically treated filamentous haemagglutinin (FHA) and pertactin
      (69 kDa) has been developed. The method uses low concentrations of antisera,
      allowing accurate and reproducible quantification of antigen content as low as 25
      microg/ml of protein for pertussis toxoid and filamentous haemagglutinin and 5
      microg/ml for pertactin. Since by the addition of detergent, diffusible subunits
      are produced irrespective of the original physical state of the antigens, the
      assay is suitable for assay of these antigens after detoxification/or
      stabilization by chemical treatment and is able to determine the differences
      between preparations which have the same protein concentration but different
      antigenic contents. This provides a means for assuring the consistency of the
      antigens after detoxification/or chemical stabilization which could be used as an
      in-process control method for acellular pertussis vaccines.

PMID- 10208724
TI  - Quality controls and in vitro diagnostic efficiency of bovine PPD tuberculins.
AB  - Wide heterogeneity was shown among different batches of bovine protein purified
      derivative (PPD) tuberculin, as regards protein content and antigenic profile.
      These features were also investigated in pilot preparations of Mycobacterium
      bovis secreted antigens and PPD tuberculins. Under controlled conditions, widely
      different compositions were revealed as a function of the M. bovis strain and
      also of the time in culture, due to the transient expression of seemingly
      important clusters of antigens. Furthermore, these parameters could dramatically
      affect the efficacy of the above preparations in in vitro assays of cell-mediated
      immunity on M. bovis-infected cattle. The field exposure to mycobacteria of the
      avium/intracellular group could also influence the readout of such assays,
      results being in agreement with a bystander suppression model of the response to
      M. bovis antigens. Due to the above, practical suggestions are put forward to
      improve the composition of bovine PPD tuberculins and the relevant control
      procedures.

PMID- 10208725
TI  - Inactivation kinetics of model and relevant blood-borne viruses by treatment with
      sodium hydroxide and heat.
AB  - To determine the efficacy of a clean-in-place system for the inactivation of
      viruses present in human plasma, the effect of 0.1 M sodium hydroxide at 60
      degrees C on viral infectivity was investigated. Inactivation of the following
      model and relevant viruses were followed as a function of time: human hepatitis A
      virus (HAV), canine parvovirus (CPV; a model for human parvovirus B-19)
      pseudorabies virus (PRV, a model for hepatitis B virus), and bovine viral
      diarrhoea virus (BVDV, a model for hepatitis C virus and human immunodeficiency
      virus). Infectivity of CPV was determined by a novel in situ EIA method which
      will prove useful for studies to validate parvovirus inactivation or removal.
      Infectivity of BVDV, PRV and CPV were shown to be reproducibly inactivated below
      the limit of detection by 0.1 M NaOH at 60 degrees C within 30 s. HAV was
      inactivated to below the limit of detection within 2 min. Treatment with heat
      alone also resulted in some log reduction for all viruses tested except for CPV
      which remained unaffected after heating at 60 degrees C for 16 min. Treatment of
      HAV with hydroxide alone (up to 1.0 m) at 15 degrees C did not lead to rapid
      inactivation. Collectively, these data suggest that 0.1 M NaOH at 60 degrees C
      for two min should be sufficient to inactivate viruses present in process
      residues.

PMID- 10208726
TI  - Laboratory tests for live attenuated poliovirus vaccine.

PMID- 10208727
TI  - Preclinical and clinical development of new vaccines.

PMID- 10208728
TI  - Meeting Announcement.

PMID- 10208729
TI  - Proliferation indices in spontaneous canine lung cancer: proliferating cell
      nuclear antigen (PCNA), Ki-67 (MIB1) and mitotic counts.
AB  - Proliferation indices were measured for specimens from 55 spontaneous canine lung
      tumours, collected by surgical biopsy from clinical patients and archived in
      paraffin wax blocks. These indices were then related to the mitotic index and
      histological type of the tumour. Proliferating cell nuclear antigen (PCNA) and Ki
      67 (MIB1) proteins were detected immunohistochemically with a biotin-streptavidin
      amplified detection system on a representative tissue section from each tumour.
      Five adjacent, non-overlapping fields were selected at random, and 200 cells per
      field were examined in each section. For PCNA, cells were classified subjectively
      into negative, weak or strong reactivity groups, based on nuclear staining. MIB1
      cells were classified as negative or positive, based on nuclear staining. Mitotic
      figures were counted in anti-PCNA-labelled and anti-MIB1-labelled sections, in
      the same tumour areas as those in which indices were established. Mitotic counts
      were also done on haematoxylin and eosin-stained tissue sections. Linear
      regression analysis showed that all PCNA, MIB1 and mitotic indices had highly
      significant positive correlations (P<0.0001) with each other. Adenosquamous and
      squamous cell carcinomas differed from other histological tumour types in having
      significantly higher proliferation indices. These data suggest that growth rates
      for lung tumours in the dog vary according to histological type. On the basis of
      differences in proliferation indices and the distribution of immunoreactivity
      between histological subtypes in this study, it would seem that
      immunohistochemical detection of PCNA and MIB/1 reactivity and analysis of
      mitotic figures in routinely processed tissues may be useful in the diagnosis of
      lung tumours. 1999 W.B. Saunders and Company Ltd.

PMID- 10208730
TI  - Macrophage populations and apoptotic cells in the liver before spontaneous
      hepatitis in Long-Evans Cinnamon (LEC) rats.
AB  - The inbred mutant strains of Long-Evans Cinnamon (LEC) rats spontaneously
      develops acute hepatitis as a result of abnormal copper accumulation, followed by
      chronic hepatitis, cholangiofibrosis and hepatocellular carcinoma. To shed some
      light on the role of macrophages in the liver failure, immunohistochemical
      methods were used to investigate the kinetics of macrophage populations in the
      liver of male LEC rats, in relation to the appearance of myofibroblastic cells
      and hepatocyte apoptosis. Rats examined at 24 weeks of age and moribund rats
      killed at 22-25 weeks of age had increased serum concentrations of aspartate
      aminotransferase and alanine aminotransferase, with jaundice and histological
      changes indicative of hepatic failure, whereas rats examined at 8, 12, 16 or 20
      weeks old showed no such abnormal findings. Immunolabelling with ED1 (a
      monoclonal antibody recognizing rat macrophages) and ED2 (a monoclonal antibody
      specific for rat resident macrophages) revealed that numbers of blood monocyte
      derived macrophages and Kupffer cells began to increase markedly at 16 weeks of
      age (before the onset of hepatitis). However, alpha-smooth muscle actin (SMA)
      positive myofibroblastic cells (modulated perisinusoidal cells) and hepatocyte
      apoptosis, demonstrable by the TUNEL method, were rarely seen at 8, 12, 16, 20 or
      24 weeks. There was no close relationship between macrophage expansion and the
      appearance of myofibroblastic cells or hepatocyte apoptosis. In moribund rats,
      only a few SMA-positive cells were seen in the periportal zones; hepatocytes
      undergoing apoptosis increased in number, and macrophages engulfing apoptotic
      bodies were observed occasionally, suggesting that apoptosis was related to
      hepatic failure as an early event. In addition, immunohistochemical examination
      demonstrated abnormal deposits of laminin along the sinusoids from 20 weeks, as
      an initial extracellular matrix protein in LEC rat livers.

PMID- 10208731
TI  - A histological and immunohistochemical study of the humoral immune system of the
      lungs in young Thoroughbred horses.
AB  - Lungs were obtained from 16 Thoroughbred horses, aged 1 day to 2 years, which had
      died or been humanely killed for reasons unrelated to disease of the lower
      respiratory tract. The lungs were then subjected to a histological and
      immunohistochemical examination of the humoral immune system. At birth there was
      no evidence of organized lymphoid tissue, and lymphocytes and plasma cells were
      virtually absent in all tissue compartments in the first week of life. However,
      by 12 weeks, foals exhibited well developed bronchus- and bronchiole-associated
      lymphoid tissue, but this had regressed progressively at 1 and 2 years of age.
      Plasma cells were present in large numbers in the walls of bronchi and
      bronchioles in foals aged 8 to 12 weeks. IgA-producing plasma cells were common
      in the lower respiratory tract of these young horses, in addition to IgG- and IgM
      producing plasma cells.

PMID- 10208732
TI  - The reproducibility of scrapie-associated fibril and PrPSc detection methods
      after long-term cold storage of natural ovine scrapie-affected brain tissue.
AB  - A pool of grey matter (medulla/brain stem, cerebellum and frontal cerebral
      cortex) was prepared from the brains of 16 sheep with scrapie, diagnosed
      clinically and by the demonstration of spongiform encephalopathy. Aliquots from
      the pool of tissue were finely chopped or homogenized and stored at +4 degrees C
      or -70 degrees C, after undergoing one of several specific pre-treatments
      (storage with or without protease inhibitors or, alternatively, with or without
      the cryoprotectant, dimethyl sulphoxide). At intervals over a period of 2 years,
      the stored extracts were examined by electron microscopy for the presence of
      scrapie-associated fibrils (SAFs) and by Western immunoblotting for the disease
      specific abnormal protein PrPSc. Throughout the 2-year period, SAFs and PrPSc
      were detected in the majority of all stored tissue extracts under all
      combinations of tissue preparation and pre-treatment. The combined detection
      rates for SAFs and PrPSc were 91% at +4 degrees C and 94% at -70 degrees C. There
      was no significant difference between the results obtained by the two detection
      methods and no specific combination of preparation method and pre-treatment was
      superior to any other. Storage of the samples at -70 degrees C appeared to give
      better results than storage at +4 degrees C, particularly with regard to fibril
      detection. For logistical reasons and ease of processing, and to avoid the
      effects of autolysis on recognizable brain regions, long-term storage at -70
      degrees C, without any pre-treatment, would appear to be the method of choice.

PMID- 10208733
TI  - Inhibition of phagosome-lysosome fusion in ovine polymorphonuclear leucocytes by
      Ehrlichia (Cytoecetes) phagocytophila.
AB  - Ehrlichia (Cytoecetes) phagocytophila, the causative agent of tick-borne fever,
      is an intracellular bacterium that survives and multiplies within granulocytes
      and monocytes. In the present study, the possible fusion of lysosomes with
      phagosomes containing E. phagocytophila was investigated in poly-morphonuclear
      (PMN) cells of sheep infected with the agent, acid phosphatase cytochemistry and
      cationized ferritin being used as markers of primary and secondary lysosomal
      enzymes. Latex beads or Candida albicans were incubated with infected and
      uninfected PMN cells and labelled with the same lysosomal markers. Lysosomal
      enzymes labelled with the markers were commonly found in phagosomes containing
      latex beads or C. albicans, but there was no evidence of phagosome-lysosome (P-L)
      fusion in phagosomes containing E. phagocytophila. It was significant that in
      cells that contained E. phagocytophila, latex beads and C. albicans, P-L fusion
      occurred only in phagosomes containing latex beads or C. albicans. However,
      evidence of P-L fusion with phagosomes containing E. phagocytophila was obtained
      when PMN cells were incubated with oxytetracycline, which is known to inhibit
      synthesis of bacterial proteins. These findings indicate that E. phagocytophila
      is capable of inhibiting P-L fusion and that oxytetracycline depresses this
      capability.

PMID- 10208734
TI  - Comparison of pathology-based techniques for detection of viscerotropic velogenic
      Newcastle disease virus in chickens.
AB  - Two pathology-based techniques, immunohistochemistry and riboprobe in-situ
      hybridization, were applied to formalin-fixed, paraffin wax-embedded tissues from
      chickens infected with three different isolates of velogenic viscerotropic
      Newcastle disease virus (VVNDV). With the immunohistochemical method, viral
      protein was consistently detectable in the spleen and caecum at the terminal
      phase of the infection. With in-situ hybridization, viral nucleic acid was
      consistently detected in the eyelid, spleen and caecum in both the acute and
      terminal phases. Hybridization with anti-sense probe to detect viral mRNA was
      often more intense than hybridization with sense probe to detect viral genomic
      RNA.

PMID- 10208735
TI  - Growth suppression and branchitis in trout exposed to hydrogen peroxide.
AB  - This study was designed to investigate the effect of single short-duration bath
      treatment with hydrogen peroxide (1000, 1250 or 1500 mg/l for 20 min), as
      currently used in treatment for sea lice, on the growth rate and gill morphology
      of rainbow trout. All three dose levels significantly reduced the specific growth
      rate of fish (22-36% reduction) during the first 3 weeks after treatment. A
      significant effect on growth rate (10-11% reduction) persisted over an additional
      3 weeks for the two highest doses. Gill lesions occurred at all three dose levels
      and also at an additional peroxide concentration of 750 mg/l; these lesions were
      characterized by large foci of epithelial hyperplasia in which lamellar fusion,
      pillar cell necrosis, and pillar channel aneurysms had developed. The proportion
      of damaged filaments showed a significant positive linear relationship with dose
      during the first 2 weeks after treatment. A significant decline in number of
      lesions occurred at 1000-1500 mg/l over the 3-week sampling period. During
      healing, necrotic lamellae were replaced by means of a pillar channel
      regenerative process.

PMID- 10208736
TI  - Morphological and histochemical analysis of a case of superficial digital flexor
      tendon injury in the horse.
AB  - This report compares the morphology and the concentrations of glycos-aminoglycans
      (GAGs) in an injured superficial digital flexor tendon (SDFT) of a horse with
      those of a normal tendon. An injured 6-year-old male Thoroughbred exhibited heat
      and swelling around the SDFT of the right forelimb. On histopathological
      examination, exuberant granulation was observed in the affected tendon, with
      activated tenocytes, angiogenesis, haemorrhage, and infiltration of small numbers
      of leucocytes. The collagen fibres were loosely packed and irregularly arranged.
      The diameter of control collagen fibrils was 20-360 nm and that of affected
      collagen fibrils 20-240 nm. In the analysis of GAGs in the matrix, hyaluronic
      acid (HA), dermatan sulphate (DS), and chondroitin sulphate (CS) were found to be
      major components in both control and affected tendons. Increases in DS in the
      affected tendon were striking. Our observations suggest that fibrillogenesis was
      activated by increases in DS and decreases in HA and CS. It is also assumed that
      absence of collagen fibrils of normal thickness and in a parallel arrangement
      reflected the morphological and biochemical characteristics of fibrillogenesis in
      the injured tendon. If the inflammatory features of an injured tendon could be
      altered, it might return eventually to its normal structure.

PMID- 10208737
TI  - Neuronal damage produced in rat brains by Clostridium perfringens type D epsilon
      toxin.
AB  - This paper reports neuronal changes in rat brains subacutely intoxicated with
      Copyright Clostridium perfringens type D epsilon toxin. Neuronal damage was
      characterized by either (1) progressive cytoplasmic vacuolation leading to
      necrosis, or (2) shrunken hyperchromatic cells with nuclear pyknosis. The
      neuronal injury was also often bilaterally symmetrical, particularly in the
      brainstem. These findings suggest that, after gaining access to brain tissue by
      producing an increase in vascular permeability, epsilon toxin later exerts a
      directly cytotoxic effect on neurons.

PMID- 10208738
TI  - Developmental competence of the gut endoderm: genetic potentiation by GATA and
      HNF3/fork head proteins.
AB  - A long-standing problem in developmental biology has been to understand how the
      embryonic germ layers gain the competence to differentiate into distinct cell
      types. Genetic studies have shown that members of the GATA and HNF3/fork head
      transcription factor families are essential for the formation and differentiation
      of gut endoderm tissues in worms, flies, and mammals. Recent in vivo footprinting
      studies have shown that GATA and HNF3 binding sites in chromatin are occupied on
      a silent gene in endoderm that has the potential to be activated solely in that
      germ layer. These and other data indicate that these evolutionarily conserved
      factors help impart the competence of a gene to be activated in development, a
      phenomenon called genetic potentiation. The mechanistic implications of genetic
      potentiation and its general significance are discussed.

PMID- 10208739
TI  - GDF5 coordinates bone and joint formation during digit development.
AB  - A functional skeletal system requires the coordinated development of many
      different tissue types, including cartilage, bones, joints, and tendons. Members
      of the Bone morphogenetic protein (BMP) family of secreted signaling molecules
      have been implicated as endogenous regulators of skeletal development. This is
      based on their expression during bone and joint formation, their ability to
      induce ectopic bone and cartilage, and the skeletal abnormalities present in
      animals with mutations in BMP family members. One member of this family,
      Growth/differentiation factor 5 (GDF5), is encoded by the mouse brachypodism
      locus. Mice with mutations in this gene show reductions in the length of bones in
      the limbs, altered formation of bones and joints in the sternum, and a reduction
      in the number of bones in the digits. The expression pattern of Gdf5 during
      normal development and the phenotypes seen in mice with single or double
      mutations in Gdf5 and Bmp5 suggested that Gdf5 has multiple functions in
      skeletogenesis, including roles in joint and cartilage development. To further
      understand the function of GDF5 in skeletal development, we assayed the response
      of developing chick and mouse limbs to recombinant GDF5 protein. The results from
      these assays, coupled with an analysis of the development of brachypodism digits,
      indicate that GDF5 is necessary and sufficient for both cartilage development and
      the restriction of joint formation to the appropriate location. Thus, GDF5
      function in the digits demonstrates a link between cartilage development and
      joint development and is an important determinant of the pattern of bones and
      articulations in the digits.

PMID- 10208740
TI  - Prostate development requires Sonic hedgehog expressed by the urogenital sinus
      epithelium.
AB  - The prostate gland develops from the urogenital sinus by a testosterone-dependent
      process of ductal morphogenesis. Sonic hedgehog (Shh) is expressed in the
      urogenital sinus epithelium and the time course of expression coincides with the
      formation of the main prostatic ducts. Expression is most abundant in the lumen
      of the urogenital sinus and in the contiguous proximal duct segments. The initial
      upregulation of Shh expression in the male urogenital sinus depends on the
      presence of testosterone. The function of Shh was examined in the male urogenital
      sinus which was transplanted under the renal capsule of an adult male host mouse.
      Blockade of Shh function by a neutralizing antibody interferes with Shh signaling
      and abrogates growth and ductal morphogenesis in the transplanted tissue. These
      observations show that testosterone-dependent Shh expression in the urogenital
      sinus is necessary for the initiation of prostate development.

PMID- 10208741
TI  - Time course of ion channel development in Xenopus muscle induced in vitro by
      activin.
AB  - During the process of mesoderm specification in Xenopus embryos, cells of the
      equatorial region are induced to form mesoderm in response to signals from the
      underlying endodermal cells. One mesodermal cell type resulting from this in vivo
      induction is skeletal muscle, which has a very specific and tightly regulated
      course of electrical and morphological development. Previously, electrical
      development could be analyzed only after neurulation, once myocytes could be
      morphologically identified. In vitro, activin triggers a cascade of events
      leading to the development of specific mesodermal tissues, including skeletal
      muscle; however, the precise role of activin in vivo is less clear. Much is now
      known about the mechanism and control of activin action, but very little is known
      about the subsequent time course of differentiation of activin-induced muscle.
      Such muscle is routinely identified by the presence of a small number of specific
      markers which, although they accurately confirm the presence of muscle, give
      little indication of the time course or quantitative aspects of muscle
      development. One of the most important functional aspects of muscle development
      is the acquisition of the complex electrical properties which allow it to
      function normally. Here we assess the ability of activin to drive in vitro the
      normal highly regulated sequence of electrical development in skeletal muscle. We
      find that in most, but not all, respects the normal time course of development of
      voltage-gated ion currents is well reproduced in activin-induced muscle. This
      characterization strengthens the case for activin as an agent capable of inducing
      the detailed developmental program of muscle and now allows for analysis of the
      regulation of electrical development prior to neurulation.

PMID- 10208742
TI  - Activation of the proteasomes of sand dollar eggs at fertilization depends on the
      intracellular pH rise.
AB  - The mechanism of the activation of intracellular proteasomes at fertilization was
      measured in living sand dollar eggs using the membrane-impermeant fluorogenic
      substrate, succinyl-Phe-Leu-Arg-coumarylamido-4-methanesulfonic acid. When the
      substrate was microinjected into unfertilized eggs, the initial velocity of
      hydrolysis of the substrate (V0) was low. V0 measured 5 to 10 min after
      fertilization was five to nine times the prefertilization level and remained high
      throughout the first cell cycle. Hydrolysis of the substrate was inhibited by
      clasto-lactacystin beta-lactone, a specific inhibitor of the proteasome. There
      has been in vitro evidence that calcium may be involved in regulation of
      proteasome activity to either inhibit the increase in peptidase activity
      associated with PA 28 binding to the 20S proteasome or stimulate activity of the
      PA 700-proteasome complex. Since both intracellular free Ca2+ concentration
      ([Ca2+]i) and intracellular pH (pHi) increase after fertilization, hydrolysis of
      the proteasome substrate was measured under conditions in which [Ca2+]i and pHi
      were varied independently during activation. When the pHi of unfertilized eggs
      was elevated by exposure to 15 mM ammonium chloride in pH 9 seawater, V0
      increased to a level comparable to that measured after fertilization. In
      contrast, [Ca2+]i elevation without pHi change, induced by calcium ionophore in
      sodium-free seawater, had no effect on V0 in the unfertilized egg. Moreover, when
      unfertilized eggs were microinjected with buffers modulating pHi, V0 increased in
      a pH-dependent manner. These results indicate that the pHi rise at fertilization
      is the necessary prerequisite for activation of the proteasome, an essential
      component in the regulation of the cell cycle.

PMID- 10208744
TI  - The centrosome-attracting body, microtubule system, and posterior egg cytoplasm
      are involved in positioning of cleavage planes in the ascidian embryo.
AB  - Many kinds of animal embryos exhibit stereotyped cleavage patterns during early
      embryogenesis. In the ascidian Halocynthia roretzi, cleavage patterns are
      invariant but they are complicated by successive unequal cleavages that occur in
      the posterior region. Here we report the essential roles of a novel structure,
      called the centrosome-attracting body (CAB), which exists in the posterior pole
      cortex of cleaving embryos, in generating unequal cleavages. By removing and
      transplanting posterior egg cytoplasm and by treatment with sodium dodecyl
      sulfate, we demonstrated that loss of the CAB resulted in abolishment of unequal
      cleavage, while ectopic formation of the CAB caused ectopic unequal cleavages to
      occur. Experiments with a microtubule inhibitor demonstrated that the centrosome
      and nucleus were attracted toward the posterior cortex, where the CAB is located,
      by shortening of microtubule bundles formed between the centrosome and the CAB.
      Consequently, the mitotic apparatus was positioned asymmetrically, resulting in
      unequal cleavage. Immunohistochemistry provided evidence that a microtubule motor
      protein, a kinesin or kinesin-like molecule, may be associated with the CAB.
      Formation of the CAB during the early cleavage stage was resistant to treatment
      with the microtubule inhibitor. In contrast, the integrity of the CAB was lost
      upon treatment with a microfilament inhibitor. We propose that the CAB plays key
      roles in the orientation and positioning of cleavage planes during unequal cell
      division.

PMID- 10208743
TI  - Defects in tracheoesophageal and lung morphogenesis in Nkx2.1(-/-) mouse embryos.
AB  - NKX2.1 is a homeodomain transcriptional factor expressed in thyroid, lung, and
      parts of the brain. We demonstrate that septation of the anterior foregut along
      the dorsoventral axis, into distinct tracheal and esophageal structures, is
      blocked in mouse embryos carrying a homozygous targeted disruption of the Nkx2.1
      locus. This is consistent with the loss of Nkx2.1 expression, which defines the
      dorsoventral boundary within the anterior foregut in wild-type E9 embryos.
      Failure in septation between the trachea and the esophagus in Nkx2.1(-/-) mice
      leads to the formation of a common lumen that connects the pharynx to the
      stomach, serving both as trachea and as esophagus, similar in phenotype to a
      human pathologic condition termed tracheoesophageal fistula. The main-stem
      bronchi bifurcate from this common structure and connect to profoundly
      hypoplastic lungs. The mutant lungs fail to undergo normal branching
      embryogenesis, consist of highly dilated sacs that are not capable of sustaining
      normal gas exchange functions, and lead to immediate postnatal death. In situ
      hybridization suggests reduced Bmp-4 expression in the mutant lung epithelium,
      providing a possible mechanistic clue for impaired branching. Functional deletion
      of Nkx2. 1 blocks pulmonary-specific epithelial cell differentiation marked by
      the absence of pulmonary surfactant protein gene expression. Altered expression
      of temporally regulated genes such as Vegf demonstrates that the lung in Nkx2.1(
      /-) mutant embryos is arrested at early pseudoglandular (E11-E15) stage. These
      results demonstrate a critical role for Nkx2.1 in morphogenesis of the anterior
      foregut and the lung as well as in differentiation of pulmonary epithelial cells.

PMID- 10208745
TI  - Dynein-dynactin function and sensory axon growth during Drosophila metamorphosis:
      A role for retrograde motors.
AB  - Mutations in the genes for components of the dynein-dynactin complex disrupt axon
      path finding and synaptogenesis during metamorphosis in the Drosophila central
      nervous system. In order to better understand the functions of this retrograde
      motor in nervous system assembly, we analyzed the path finding and arborization
      of sensory axons during metamorphosis in wild-type and mutant backgrounds. In
      wild-type specimens the sensory axons first reach the CNS 6-12 h after puparium
      formation and elaborate their terminal arborizations over the next 48 h. In
      Glued1 and Cytoplasmic dynein light chain mutants, proprioceptive and tactile
      axons arrive at the CNS on time but exhibit defects in terminal arborizations
      that increase in severity up to 48 h after puparium formation. The results show
      that axon growth occurs on schedule in these mutants but the final process of
      terminal branching, synaptogenesis, and stabilization of these sensory axons
      requires the dynein-dynactin complex. Since this complex functions as a
      retrograde motor, we suggest that a retrograde signal needs to be transported to
      the nucleus for the proper termination of some sensory neurons.

PMID- 10208746
TI  - A mouse cerberus/Dan-related gene family.
AB  - The Xenopus cerberus gene is able to induce ectopic heads in Xenopus embryos. At
      the time of its identification, cerberus shared significant homology with only
      one other protein, the putative rat tumor suppressor protein Dan. Sequence
      analysis has revealed that cerberus and Dan are members of a family of predicted
      secreted proteins, here called the can family. The identification of a can-family
      member in the nematode Caenorhabditis elegans, CeCan1, suggests that this family
      is of ancient origin. In the mouse, there are at least five family members: Cer1,
      Drm, PRDC, Dan, and Dte. These genes are expressed in patterns that suggest that
      they may play important roles in patterning the developing embryo. Cer1 marks the
      anterior visceral endoderm at E6.5. Dte is expressed asymmetrically in the
      developing node. Dan is first seen in the head mesoderm of early head fold stage
      embryos and Drm is expressed in the lateral paraxial mesoderm at E8.5. The region
      of homology shared by these genes, here called the can domain, closely resembles
      the cysteine knot motif found in a number of signaling molecules, such as members
      of the TGFbeta superfamily. Epitope-tagged versions of Cer1 show that, unlike in
      TGFbeta superfamily members, the cysteine knot motif is not processed away from a
      proprotein. Recent experiments in Xenopus have suggested that cerberus may act as
      an inhibitor of BMP signaling. To examine this further, the ability of Dan, Cer1,
      and human DRM to attenuate Bmp4 signaling has been assessed in P19 cells using
      pTlx-Lux, a BMP-responsive reporter. All three genes are able to inhibit Bmp4
      signaling. These data suggest that the different family members may act to
      modulate the action of TGFbeta family members during development.

PMID- 10208747
TI  - The Caenorhabditis elegans mel-11 myosin phosphatase regulatory subunit affects
      tissue contraction in the somatic gonad and the embryonic epidermis and
      genetically interacts with the Rac signaling pathway.
AB  - Caenorhabditis elegans embryonic elongation is driven by cell shape changes that
      cause a contraction of the epidermal cell layer enclosing the embryo. We have
      previously shown that this process requires a Rho-associated kinase (LET-502) and
      is opposed by the activity of a myosin phosphatase regulatory subunit (MEL-11).
      We now extend our characterization and show that mel-11 activity is required both
      in the epidermis during embryonic elongation and in the spermatheca of the adult
      somatic gonad. let-502 and mel-11 reporter gene constructs show reciprocal
      expression patterns in the embryonic epidermis and the spermatheca, and mutations
      of the two genes have opposite effects in these two tissues. These results are
      consistent with let-502 and mel-11 mediating tissue contraction and relaxation,
      respectively. We also find that mel-11 embryonic inviability is genetically
      enhanced by mutations in a Rac signaling pathway, suggesting that Rac potentiates
      or acts in parallel with the activity of the myosin phosphatase complex. Since
      Rho has been implicated in promoting cellular contraction, our results support a
      mechanism by which epithelial morphogenesis is regulated by the counteracting
      activities of Rho and Rac.

PMID- 10208748
TI  - Distinct 5' SCL enhancers direct transcription to developing brain, spinal cord,
      and endothelium: neural expression is mediated by GATA factor binding sites.
AB  - The SCL gene encodes a basic helix-loop-helix transcription factor with a pivotal
      role in the development of endothelium and of all hematopoietic lineages. SCL is
      also expressed in the central nervous system, although its expression pattern has
      not been examined in detail and its function in neural development is unknown. In
      this article we present the first analysis of SCL transcriptional regulation in
      vivo. We have identified three spatially distinct regulatory modules, each of
      which was both necessary and sufficient to direct reporter gene expression in
      vivo to three different regions within the normal SCL expression domain, namely,
      developing endothelium, midbrain, and hindbrain/spinal cord. In addition we have
      demonstrated that GATA factor binding sites are essential for neural expression
      of the SCL constructs. The midbrain element was particularly powerful and axonal
      lacZ expression revealed the details of axonal projections, thus implicating SCL
      in the development of occulomotor, pupillary, or retinotectal pathways. The
      neural expression pattern of the SCL gene was highly conserved in mouse, chicken,
      and zebrafish embryos and the 5' region of the chicken SCL locus exhibited a
      striking degree of functional conservation in transgenic mice. These data suggest
      that SCL performs critical functions in neural development. The regulatory
      elements identified here provide important tools for analyzing these functions.

PMID- 10208749
TI  - Rib truncations and fusions in the Sp2H mouse reveal a role for Pax3 in
      specification of the ventro-lateral and posterior parts of the somite.
AB  - The splotch (Pax3) mouse mutant serves as a model for developmental defects of
      several types, including defective migration of dermomyotomal cells to form the
      limb musculature. Here, we describe abnormalities of the ribs, neural arches, and
      acromion in Sp2H homozygous embryos, indicating a widespread dependence of
      lateral somite development on Pax3 function. Moreover, the intercostal and body
      wall muscles, derivatives of the ventrolateral myotome, are also abnormal in Sp2H
      homozygotes. Pax3 is expressed in the dermomyotome, but not in either the
      sclerotome or the myotome, raising the possibility that Pax3-dependent inductive
      influences from the dermomyotome are necessary for early specification of lateral
      sclerotome and myotome. Support for this idea comes from analysis of gene
      expression markers of lateral sclerotome (tenascin-C and scleraxis) and myotome
      (myogenin, MyoD, and Myf5). All exhibit ventrally truncated domains of expression
      in Sp2H homozygotes, potentially accounting for the rib and intercostal muscle
      truncations. In contrast, the medial sclerotomal marker Pax1 is expressed
      normally in mutant embryos, arguing that Pax3 is not required for development of
      the medial sclerotome. Most of the somitic markers show ectopic expression in
      anteroposterior and mediolateral dimensions, suggesting a loss of definition of
      somite boundaries in splotch and explaining the rib and muscle fusions. An
      exception is Myf5, which is not ectopically expressed in Sp2H homozygotes,
      consistent with the previous suggestion that Pax3 and Myf5 function in different
      pathways of skeletal myogenesis. PDGFalpha and its receptor are candidates for
      mediating signalling between myotome and sclerotome. We find that both genes are
      misexpressed in Sp2H embryos, suggesting that PDGFalpha/PDGFRalpha may function
      downstream of Pax3, accounting for the close similarities between the splotch and
      Patch mutant phenotypes. Our findings point to additional regulatory functions
      for the Pax3 transcription factor, apart from those already demonstrated for
      development of the neural tube, neural crest, and dermomyotome.

PMID- 10208750
TI  - bves: A novel gene expressed during coronary blood vessel development.
AB  - We have used a subtractive method to clone novel messages enriched in the heart.
      Here we show that one such message, bves (blood vessel/epicardial substance) is a
      novel protein that is highly conserved between chicken and mouse. The bves
      message is detected at high levels in early chick hearts. Using anti-Bves
      antibodies, we show expression in cells of the proepicardial organ, migrating
      epicardium, epicardial-derived mesenchyme, and smooth muscle of the developing
      intracardiac arterial system, including the coronary arteries. Our data suggest
      that Bves is an early marker of developing vascular smooth muscle cells. In
      addition, the expression pattern of Bves protein reveals the patterning of
      intracardiac vascular smooth muscle and possible insights into the cellular
      regulation of smooth muscle differentiation during vasculogenesis.

PMID- 10208751
TI  - Spatiotemporal dynamics of the [Ca2+]i rise induced by microinjection of sperm
      extract into mouse eggs: preferential induction of a Ca2+ wave from the cortex
      mediated by the inositol 1,4,5-trisphosphate receptor.
AB  - Hamster sperm extract (SE) possessing Ca2+ oscillation-inducing activity was
      microinjected into the peripheral or central region of mouse eggs, and the first
      increase in intracellular Ca2+ concentration ([Ca2+]i), together with the spread
      of fluorescence-labeled SE in the ooplasm, was investigated by imaging with
      confocal microscopy. Injection into the periphery always induced a Ca2+ wave that
      started from the injection site after a delay of 5 to 30 s depending on the
      concentration of SE. The diluted SE caused a wave of two-step [Ca2+]i rises,
      which was always observed at fertilization. Injection into the center could
      induce a radial Ca2+ wave with relatively high dose of SE, but lower dose of SE
      caused a [Ca2+]i rise after a longer delay which was initiated synchronously over
      the ooplasm or was preceded in a peripheral area. Injection of diluted SE
      remarkably prolonged the delay time and reduced the rate of [Ca2+]i rise. The
      critical concentration of SE needed to induce [Ca2+]i rise was significantly
      lower in the periphery. These results indicate that the sensitivity to SE is
      higher in the cortex. SE-induced [Ca2+]i rises were blocked by an antibody
      against the type 1 inositol 1,4,5-trisphosphate receptor (InsP3R). The cortex was
      substantially more sensitive to injected InsP3 induction of Ca2+ release than the
      center. It is suggested that the cortex of mouse eggs may involve a functionally
      specialized organization of InsP3Rs and Ca2+ pools in which a cytosolic sperm
      factor(s) could act upon sperm-egg fusion to cause Ca2+ release, leading to the
      Ca2+ wave at fertilization.

PMID- 10208752
TI  - Ca2+ is required for phosphorylation of clam p82/CPEB in vitro: implications for
      dual and independent roles of MAP and Cdc2 kinases.
AB  - During early development gene expression is controlled principally at the
      translational level. Oocytes of the surf clam Spisula solidissima contain large
      stockpiles of maternal mRNAs which are translationally dormant or masked until
      meiotic maturation. Fertilisation of the oocyte leads to rapid polysomal
      recruitment of the abundant cyclin and ribonucleotide reductase mRNAs at about
      the time they undergo cytoplasmic polyadenylation. Clam p82, a 3' UTR RNA-binding
      protein, and a member of the CPEB (cytoplasmic polyadenylation element binding
      protein) family, functions as a translational masking factor in oocytes and as a
      polyadenylation factor in fertilised eggs. In meiotically maturing clam oocytes,
      p82/CPEB is rapidly phosphorylated on multiple residues to a 92-kDa apparent
      size, prior to its degradation during the first cell cleavage. Here we examine
      the protein kinase(s) that phosphorylates clam p82/CPEB using a clam oocyte
      activation cell-free system that responds to elevated pH, mirroring the pH rise
      that accompanies fertilisation. We show that p82/CPEB phosphorylation requires
      Ca2+ (<100 microM) in addition to raised pH. Examination of the calcium
      dependency combined with the use of specific inhibitors implicates the combined
      and independent actions of cdc2 and MAP kinases in p82/CPEB phosphorylation.
      Calcium is necessary for both the activation and the maintenance of MAP kinase,
      whose activity is transient in vitro, as in vivo. While cdc2 kinase plays a role
      in the maintenance of MAP kinase activity, it is not required for the activation
      of MAP kinase. We propose a model of clam p82/CPEB phosphorylation in which MAP
      kinase initially phosphorylates clam p82/CPEB, at a minor subset of sites that
      does not alter its migration, and cdc2 kinase is necessary for the second wave of
      phosphorylation that results in the large mobility size shift of clam p82/CPEB.
      The possible roles of phosphorylation for the function and regulation of p82/CPEB
      are discussed.

PMID- 10208753
TI  - G-protein betagamma subunit-dependent phosphorylation of 62-kDa protein in the
      early signaling pathway of starfish oocyte maturation induced by 1-methyladenine.
AB  - In starfish oocytes, maturation is induced by a hormone, 1-methyladenine (1-MA),
      that binds to the receptors exposed to the outer surface of the plasma membrane.
      The signal of 1-MA stimulates the heterotrimeric G protein, resulting in
      dissociation of the betagamma subunit of G protein (Gbetagamma) from a pertussis
      toxin-sensitive Gi-type alpha subunit. To investigate the targets for Gbetagamma,
      we analyzed 1-MA- or Gbetagamma-dependent phosphorylation using in vivo and in
      vitro systems. A 62-kDa protein was phosphorylated immediately after 1-MA
      treatment in intact oocytes. In the cell-free preparations, the 62-kDa protein
      was also phosphorylated on serine residue(s) immediately after addition of 1-MA
      or Gbetagamma. The Gbetagamma-dependent phosphorylation of the 62-kDa protein was
      inhibited by wortmannin or LY294002, which are mechanistically different
      inhibitors of phosphatidylinositol 3-kinase (PI3K). LY294002 also inhibited
      Gbetagamma- as well as 1-MA-induced maturation of oocytes. Taken together, these
      results indicate that the 62-kDa protein functions downstream of Gbetagamma and
      PI3K in the early signaling pathway of 1-MA-induced starfish oocyte maturation.
      The phosphorylation of the 62-kDa protein may be required for the activation of
      maturation-promoting factor.

PMID- 10208754
TI  - Pharmacologic modulation of protein kinase C isozymes: the role of RACKs and
      subcellular localisation.
AB  - Protein kinase C (PKC) isozymes are highly homologous kinases and several
      different isozymes can be present in a cell. Each isozyme is likely to mediate
      unique functions, but pharmacological tools to explore their isozyme-specific
      roles have not been available until recently. In this review, we describe the
      development and application of isozyme-selective inhibitors of PKC. The
      identification of these inhibitors stems from the observation that PKC isozymes
      are each localised to unique subcellular locations following activation.
      Inhibitors of this isozyme-unique localisation have been shown to act as
      selective inhibitors of the functions of individual isozymes. The identification
      of isozyme-specific inhibitors should allow the exploration of individual PKC
      isozyme function in a wide range of cell systems.

PMID- 10208755
TI  - Role of endogenous serotonin and histamine in the pathogenesis of gastric mucosal
      lesions in unanaesthetised rats with a single treatment of compound 48/80, a mast
      cell degranulator.
AB  - In unanaethetised rats with a single injection of compound 48/80, a mast cell
      degranulator (0.75 mg kg-1, i.p.), gastric lesions occurred with increased serum
      serotonin and histamine levels and reduced gastric mucosal blood flow at 0.5 h
      after the injection and developed at 3 h. Pretreatment with either cyproheptadine
      (a serotonin and histamine antagonist) or methysergide (a serotonin antagonist)
      prevented the formation of gastric mucosal lesions with attenuation of reduced
      gastric mucosal blood flow at 0.5 h after compound 48/80 injection, while
      pretreatment with either amitriptyline (a selective inhibitor of histamine
      release from mast cells), tripelennamine (a histamine H1-receptor antagonist),
      famotidine (a histamine H2-receptor antagonist) or cimetidine (a histamine H2
      receptor antagonist) had no effect. Pretreatment with either cyproheptadine,
      methysergide, amitriptyline or tripelennamine prevented the development of
      gastric mucosal lesions at 3 h after compound 48/80 injection, while pretreatment
      with either famotidine or cimetidine had no effect. These results indicate that
      in unanaesthetised rats with a single compound 48/80 treatment, acutely released
      endogenous serotonin causes gastric mucosal lesions, while released endogenous
      histamine mainly contributes to the lesion development and that gastric acid
      plays little role in the pathogenesis of the compound 48/80-induced acute gastric
      lesions.

PMID- 10208756
TI  - Spotlight on the continual applicability of routine plasma monitoring
      antiepileptic drugs in the treatment of epilepsy.
AB  - The continual applicability of routine plasma measurement of antiepileptic drugs
      (AEDS) was assessed in 301 epileptic patients with mean age and body weight+/-SD
      of 30+/-10.6 years and 55+/-19 kg, respectively. The AEDS used included
      carbamazepine (CBZ), phenytoin (PHT) or valproic acid (VPA) which were given
      either alone (monotherapy) or in combination (polytherapy). The incidence of
      uncontrolled epilepsy was significantly higher (P<0.001) in polytherapy vs
      monotherapy of AEDS and when plasma levels of the drugs were in the
      subtherapeutic range (P<0.01 for PHT, and P<0.001 for CBZ). Subtherapeutic levels
      of CBZ were seen with fixed and reasonable doses of 600 mg of the drug given
      daily. Also, the concentration dose ratios of AEDS were significantly lower in
      polytherapy vs monotherapy. In conclusion, routine plasma monitoring of AEDS
      especially in uncontrolled cases of epilepsy could be considered as a fast tool
      for proper therapeutic approach and dose optimisation in these psychologically
      and socially devastating episodes.

PMID- 10208757
TI  - Lithium chloride-induced cardiovascular changes in rabbits are mediated by
      adenosine triphosphate-sensitive potassium channels.
AB  - The effect of lithium chloride on the mean arterial blood pressure, heart rate
      and heart contractility was evaluated in rabbits. The intravenous administration
      of 50 mg kg-1 lithium chloride as a bolus injection into rabbits produced a
      progressive decrease in the mean arterial blood pressure, heart rate and heart
      contractility during the 2-h period of investigation. Pretreatment of animals
      with 5 mg kg-1 glibenclamide, a potent inhibitor of adenosine triphosphate
      sensitive potassium channels, markedly inhibited the cardiovascular changes
      induced by lithium chloride. Doubling the dose of glibenclamide nearly abolished
      these effects of lithium chloride. Similarly, lithium chloride produced a
      concentration- dependent relaxation of noradrenaline-induced contractions in
      isolated aortic strips of rabbits. This relaxant effect of lithium chloride was
      inhibited by pretreatment of the aortic strips with glibenclamide. Doubling the
      concentration of glibenclamide in the bathing fluid nearly abolished the effect
      of lithium. Diazoxide and verapamil potentiated the relaxant effect of lithium
      chloride on the isolated noradrenaline-contracted aortic strips. Pretreatment
      with glibenclamide markedly reversed the effect of diazoxide but not that of
      verapamil. The intravenous administration of lithium was also found to be capable
      of increasing the plasma potassium level and of decreasing the intracellular
      levels of adenosine triphosphate in cardiac and vascular tissues in a time
      dependent manner. The plasma sodium and calcium levels were not changed. These
      results provide evidence that the hypotensive and cardiac depressant effects of
      lithium chloride are mediated by activation of adenosine triphosphate-sensitive
      potassium channels.

PMID- 10208758
TI  - Midazolams cardiac depressant effects and their lack of reversal by flumazenil in
      isolated rabbit hearts.
AB  - Midazolam is known to cause a dose-dependent increase and decrease in the
      contractile force of the myocardium. Whether flumazenil can reverse these effects
      of midazolam remains unclear. In this study, we determined the cardiac effects of
      midazolam and the counter effect of flumazenil on midazolam-induced myocardial
      depression in isolated rabbit hearts. Rabbit hearts were isolated and perfused
      using the Langendorff technique, and left ventricle pressure and heart rate were
      measured by a pressure transducer in the left ventricle. One set of hearts were
      perfused with increasing concentrations of midazolam for 10 min, another set were
      perfused with concomitant midazolam and flumazenil. Concentrations of 5, 10, 20
      and 50 microM midazolam decreased left ventricle pressure significantly (P <
      0.01, P < 0.05, P < 0.01, P < 0.01, respectively). Heart rates decreased with
      concentrations of 10, 20 and 50 microM midazolam (P < 0.01, P < 0.01, P < 0.05,
      respectively). Flumazenil had no effect on the midazolam-induced decrease in left
      ventricle pressure and heart rate. Midazolam decreased the cardiac contractile
      force and heart rate of isolated rabbit hearts in a concentration-dependent
      manner. The failure of flumazenil to reverse these effects suggest that this
      cardiac depressant effect of midazolam is not mediated through peripheral
      benzodiazepine receptors.

PMID- 10208759
TI  - Reversal of doxorubicin-induced cardiac metabolic damage by L-carnitine.
AB  - Biopharmacological evaluations of the protective effects of L-carnitine (a
      naturally occurring quaternary ammonium compound) against doxorubicin-induced
      metabolic damage were carried out in isolated cardiac myocytes and in isolated
      rat heart mitochondria. Perfusion of the heart with DOX (0.5 mM) caused a
      significant 70% inhibition of palmitate oxidation in cardiac myocytes, while L
      carnitine (5 mM) perfusion caused stimulation which accounted for 37%. Perfusion
      of the heart with L-carnitine after 10-min perfusion with DOX (0.5 mM) caused 88%
      reversal of DOX-induced inhibition of palmitate oxidation in cardiac cells. In
      rat heart mitochondria, DOX has no effect on either palmitate oxidation or acyl
      CoA synthetase activity, whereas Enoximone (c-AMP-dependent phosphodiesterase
      inhibitor), caused a significant inhibition of palmitate oxidation and acyl-CoA
      activity (40 and 27%, respectively). The oxidation of palmitoyl-CoA, an index of
      carnitine palmitoyltransferse reaction was significantly inhibited by DOX as a
      function of DOX concentration. Preincubation of mitochondria with L-carnitine
      caused reversal of DOX-induced inhibition of palmitoyl-CoA oxidation depending on
      the concentration of L-carnitine. Moreover, L-carnitine treatment did not
      interfere with the cytotoxic effect of doxorubicin against the growth of solid
      Ehrlich carcinoma. The findings of this study may suggest that inhibition of
      fatty acid oxidation in the heart is at least a part of doxorubicin
      cardiotoxicity and that L-carnitine can be used to prevent the doxorubcin-induced
      cardiac metabolic damage without interfering with its antitumour activities.

PMID- 10208760
TI  - Modifications of receptor concentrations for adrenaline, steroid hormones,
      prostaglandin F2alpha and gonadotropins in hypophysis and ovary of dairy cows
      with ovarian cysts.
AB  - Receptor concentrations for adrenaline, steroid hormones, PGF2alpha, LH and FSH
      were measured in the hypophysis and ovary of dairy cows with ovarian cysts and
      the results were compared with those of healthy animals. Significant
      modifications were found in all receptor concentrations, either between
      follicular and luteal structures or between the hypophyseal and ovarian
      receptorial status. The correlations between catecholaminergic and steroidal
      systems have already been demonstrated, particularly those existing between beta
      adrenoceptors and steroid hormone receptors. Particular attention has been given
      to the possibility that a derangement in neurogenic inputs may be at the basis of
      some ovarian pathologies. The results of the present study suggest that the
      modifications of the ovarian and hypophyseal receptorial status of healthy and
      affected cows could play an important role in the pathogenesis of ovarian cysts.

PMID- 10208761
TI  - Absence epilepsy and regional blood-brain barrier permeability: the effects of
      pentylenetetrazole-induced convulsions.
AB  - This study was designed to evaluate the blood-brain barrier permeability
      characteristics of the WAG/Rij strain of rats that are an ideal model for human
      absence epilepsy, in controls and pentylenetetrazole-induced seizures conditioned
      to Evans blue-albumin. For this, WAG/Rij and Wistar rats were treated with either
      saline or 55 mg kg-1 pentylenetetrazole i.v. after the rats were injected with 3
      ml kg-1 of 2% Evans blue. Total duration of seizure activity and regional blood
      brain barrier permeability changes were determined and compared with control
      Wistar rats. The duration of convulsive activity which was induced by
      pentylenetetrazole was significantly longer in WAG/Rij rats than in Wistar rats.
      The blood-brain barrier opening to Evans blue was not the case in saline-
      injected WAG/Rij or Wistar rats, but this was clearly seen in both strains after
      pentylenetetrazole-induced convulsions. EB leakage was mainly seen in the
      cortical areas, cerebellum, pons, thalamus, hypothalamus and corpus striatum of
      WAG/Rij rat brain, whereas this was recorded in the preoptic area, bulbus
      olfactorius, midbrain, hypothalamus, corpus striatum and inferior colliculus of
      the Wistar rats brain. As a result, the WAG/Rij rats were more susceptible than
      Wistar rats to PTZ-induced generalised tonic-clonic convulsions, and a different
      pattern in PTZ-induced changes in BBB permeability was observed between WAG/Rij
      rats and Wistar rats.

PMID- 10208762
TI  - The importance of the number of NMDA receptors in the development of
      supersensitivity or tolerance to and dependence on morphine.
AB  - Opiate or NMDA receptor antagonists given during and/or after the development of
      tolerance and dependence have been reported to prevent these developments. In the
      present study, MK801 (dizolcipine) and naltrexone (NX), two antagonists of NMDA
      and opiate receptors, respectively were used in rats to find any correlations
      between changes in NMDA receptor kinetics, and the intensity of tolerance and
      dependence. Thus, six different groups of rats were formed. The rats in the
      groups were given saline (S)+S, S+morphine (M), NX+S, NX+M, MK801+S and MK801+M,
      respectively, once per day for 8 days. On day 9, the rats from each group were
      divided into four subgroups. The rats of the first subgroup were subjected to the
      determination of tail-flick latency. The rats of the second subgroup were
      administered 1 mg kg-1 naloxone (NL) 2 h after administration of 3 mg kg-1M. The
      rats of the third subgroup were implanted with two M pellets and after 72 h they
      were challenged with NL. The remaining rats received drugs also on day 9
      according to the previous administration paradigm. Two hours after the
      administrations, their brains were utilised for the determination of NMDA
      receptor kinetics, employing [3H]glutamate. The measurement of tail-flick latency
      showed the prevention by NX or MK801 of the development of tolerance to M. The
      rats, which were administered 3 mg kg-1M 2 h before 1 mg kg-1 NL injection, on
      day 9 showed that only NX given previously along with M attenuated the intensity
      of the development of M dependence. NX administered alone intensified the
      development of dependence on a single dose of M. The development of M dependence
      upon the M pellet implantation was intensified by the previous administration of
      NX or MK801 concomitantly with M. The administration of M or MK801 alone, or NX
      together with M, caused significant upregulation of NMDA receptors. NX alone, and
      MK801 given concurrently with M led to a significant downregulation. So, in light
      of the previous findings and the present experimental data it can be said that:
      (1) supersensitivity to opioids may be a downregulation of NMDA as well as an
      upregulation of the opioid receptor; (2) either upregulation or downregulation of
      NMDA receptors may facilitate subsequent development of opioid dependence; (3)
      tolerance to opioid may necessitate both upregulation of NMDA receptors and
      downregulation of opioid receptors; and (4) beneficial effects of opioid
      antagonists in the treatment of opiate dependence and CNS injuries may be
      strongly related to the down regulation of NMDA receptors.

PMID- 10208763
TI  - Antibacterial activity of gentamicin and ciprofloxacin against Gram-negative
      bacteria: interactions with pig and calf sera.
AB  - The antibacterial activity of pig and calf serum and its ability to interact with
      gentamicin and ciprofloxacin were studied in vitro using Escherichia coli K-12,
      Proteus rettgeri (Sanelli) and Klebsiella pneumoniae ATCC 10031. The
      antimicrobial activity of the above drugs, alone or in combination with serum,
      was investigated by the checkerboard method and expressed as the minimal
      inhibitory concentration (microg ml-1). Pig serum (25%) with gentamicin had a
      synergistic antibacterial effect against Escherichia coli K-12 and pig serum
      (25%) with ciprofloxacin against Proteus rettgeri (Sanelli) and Klebsiella
      pneumoniae ATCC 10031. Calf serum (25%) had a synergistic effect with gentamicin
      against Proteus rettgeri (Sanelli) and calf serum (25%) plus ciprofloxacin
      against Klebsiella pneumoniae ATCC 10031. The effects of these drugs may be
      enhanced by pig and calf sera.

PMID- 10208764
TI  - Preventive effect of teprenone on stress-induced gastric mucosal lesions and its
      relation to gastric mucosal constitutive nitric oxide synthase activity.
AB  - Recently, we demonstrated that teprenone, an anti-ulcer agent, exerts protective
      and preventive actions against water immersion restraint (WIR) stress-induced
      gastric mucosal lesions in rats both by inhibiting neutrophil infiltration into
      the gastric mucosal tissue and by preserving gastric mucus synthesis and
      secretion. In rats with WIR stress we have also found a decrease in gastric
      mucosal constitutive nitric oxide synthase (cNOS) activity and a drastic increase
      in gastric mucosal inducible nitric oxide synthase (iNOS) activity. The decrease
      in gastric mucosal cNOS activity is closely related to an increase in neutrophil
      infiltration into the gastric mucosa and a decrease in the level of gastric
      mucus. In this study of WIR-stressed rats, therefore, we examined whether the
      inhibitory actions of teprenone on neutrophil infiltration and decreases in mucus
      synthesis and secretion in the gastric mucosa of rats are related to the change
      in gastric mucosal cNOS activity during the development of gastric mucosal
      lesions. Pre-administration of teprenone (200 mg kg-1) prevented the decrease in
      gastric mucosal cNOS activity with attenuations of neutrophil infiltration into
      gastric mucosal tissues and decreased levels of gastric mucosal hexosamine, an
      index of gastric mucin, and adherent mucus in rats with 3 or 6 h of WIR stress.
      These preventive effects of teprenone on the gastric mucosal neutrophil
      infiltration and the decrease in gastric mucus levels in rats with WIR stress
      were completely reversed with inhibition of gastric mucosal cNOS activity by co
      administration of NG-monomethyl L-arginine (L-NMMA), a non-selective NOS
      inhibitor. These results suggest that the inhibitory actions of teprenone on
      neutrophil infiltration and decreases in mucus synthesis and secretion in the
      gastric mucosa of rats with WIR stress are closely related to the maintenance of
      cNOS activity in the gastric mucosal tissue.

PMID- 10208765
TI  - The effects of an "El Nino" southern oscillation event on reproduction in male
      and female blue-footed boobies, Sula nebouxii.
AB  - This study attempted to determine endocrine correlates of reproductive success in
      relation to major deleterious environmental conditions. In 1992, an El Nino
      southern oscillation event resulted in complete reproductive failure in a colony
      of blue-footed boobies, Sula nebouxi, on Isla Isabel in the Pacific Ocean off San
      Blas, Nayarit, Mexico (21.5 degrees N, 105.5 degrees W). In 1993, the El Nino
      event had waned and reproductive success was high. The mean sea surface
      temperature in 1992 was 26.69 degrees, the warmest year for 11 years of data
      (mean, 25.63 degrees ). In 1993, mean sea surface temperature was 25.75 degrees.
      Plasma levels of testosterone were highest during the egg-laying period in 1993
      and declined markedly during incubation. There were no differences between males
      and females. Comparisons of testosterone levels between 1992 and 1993 (egg-laying
      time point removed for 1993) showed no significant differences. Thus reproductive
      failure during an El Nino year was not related to testosterone levels. Baseline
      plasma levels of corticosterone did not change over the nesting cycle in either
      sex. There was a trend for plasma levels of corticosterone to be higher in males
      and females during the earlier stages of breeding in 1992 compared with 1993, and
      if all levels were combined within years then females showed significantly higher
      plasma levels of corticosterone in the El Nino year. Plasma levels of
      corticosterone showed marked increases following capture and handling in both
      sexes and at every stage of the breeding cycle in each year. There was no
      variation in the adrenocortical responses to stress with year or stage of nesting
      in males. However, in females, maximum corticosterone levels were greatest during
      the parental phase of 1992, the El Nino year, when all nests ultimately failed.
      Comparisons of the dynamics of corticosterone changes during the capture stress
      protocol revealed no correlations with body mass in 1992 or 1993. These data
      suggest that although massive reproductive failure in the El Nino year was not
      related to testosterone levels, baseline circulating concentrations of
      corticosterone may have a role in inhibiting onset of breeding. In contrast,
      after the nesting cycle has been initiated, increased adrenocortical sensitivity
      to acute stress may be involved in nest abandonment.

PMID- 10208766
TI  - Androgen receptors in two androgen-mediated, sexually dimorphic characters of
      frogs.
AB  - The presence/absence of androgen receptors is examined in two sexually dimorphic
      features of frogs: the nuptial pad and the external oblique muscle.
      Immunohistochemistry reveals that both males and females possess androgen
      receptors in these tissues. Males have a higher density of immunopositive nuclei
      in the oblique muscle than do females. The presence of androgen receptors in both
      male and female tissues is consistent with results from hormone experiments in
      which androgen supplements induce the expression of a nuptial pad and enlarge the
      external oblique muscles in castrated males and ovariectomized females.

PMID- 10208767
TI  - Somatolactin in the white sturgeon and African lungfish and its evolutionary
      significance.
AB  - Somatolactin (SL) is a newly characterized pituitary hormone belonging to the
      growth hormone-prolactin family. Until now SL has been identified only in
      teleosts, the most highly derived ray-finned fishes. We report here the cloning
      of SL cDNAs from two species of bony fish, the white sturgeon (Acipenser
      transmontanus) and the African lungfish (Protopterus annectens). Overlapping
      partial cDNA clones corresponding to teleost SLs were amplified by polymerase
      chain reaction (PCR) from either single-strand or double-strand cDNA from
      pituitary glands. Excluding the poly(A) tail, the sturgeon SL cDNA is 881 base
      pairs (bp). This is comparable to 1.0 kb estimated by Northern blot analysis. It
      contains a 696-bp open reading frame encoding a prehormone of 232 amino acids
      (aa) with a signal peptide of 24 aa and a mature protein of 208 aa. Excluding the
      poly(A) tail, the lungfish SL cDNA is 938 bp. This is comparable to 1.1 kb
      estimated by Northern blot analysis. It contains a 696-bp open reading frame
      encoding a prehormone of 232 aa with a signal peptide of 26 aa and a mature
      protein of 206 aa. The deduced aa sequences of sturgeon and lungfish SLs show 76
      60% and 65-54% identity with teleost SLs, respectively. These values are
      significantly higher than the 30% identity with nonteleostean growth hormones and
      prolactins. Immunostaining of sturgeon pituitary with anti-salmon SL serum
      demonstrated that the SL cells were localized in the pars intermedia, as in
      teleosts. The present results demonstrate that the SL gene is present in two
      divergent lineages, the Actinopterygii (Chondrostei: white sturgeon) and the
      Sarcopterygii (Dipnoi: African lungfish).

PMID- 10208768
TI  - Endocrine pancreatic cells from Xenopus laevis: light and electron microscopic
      studies.
AB  - Insulin, glucagon, pancreatic polypeptide (PP), peptide tyrosine tyrosine (PYY),
      somatostatin (SST)-28 (1-12), salmon (s) SST-25, and SST-14 immunoreactivities
      were demonstrated in the pancreatic endocrine cells of Xenopus laevis using light
      and electron microscopic immunocytochemistry. Insulin-, SST-28 (1-12)/SST-14-,
      and PYY-immunoreactive (ir) cells were found throughout the pancreas either
      isolated in small clusters of a single cell type or, except in the case of PYY-ir
      cells, forming islets consisting of various cell types. Anti-sSST-25 serum
      detected the invariant SST-14 form. Cells that were only immunoreactive to
      glucagon were isolated or clustered in the duodenal lobe, while in the splenic
      lobe cells immunoreactive to both glucagon and PP were observed in isolation,
      clustered, or in the periphery of the islets. There were no cells that were
      immunoreactive only to PP or to NPY. Ultrastructurally, the endocrine cells were
      characterized by their secretory granules, which were immunogold labeled with the
      corresponding antisera. Insulin cells had large round secretory granules with a
      round, irregular, or crystalline-like dense core. Glucagon-ir cells had round
      secretory granules with a dense core and a clear halo. Glucagon/PP- and PYY-ir
      cells showed round, ovoid, or pear-shaped secretory granules, which were larger
      and less electron dense in the latter cell type. The secretory granules of SST-ir
      cells were ovoid or bacillary with a medium electron-dense content. A sixth cell
      type with very small secretory granules could only be characterized by
      conventional electron microscopy, since it did not immunoreact with any of the
      antisera applied in this study.

PMID- 10208769
TI  - Teleost-type angiotensin is present in Australian lungfish, Neoceratodus
      forsteri.
AB  - Angiotensin I (ANG I) was produced from the incubation of lungfish plasma with
      homologous kidney extracts. The purified peptide was found to have the sequence
      of H-Asn-Arg-Val-Tyr-Val-His-Pro-Phe-Thr-Leu-OH, which is homologous for the
      first eight residues with all teleost angiotensins so far sequenced, although
      lungfish generally possess tetrapod-type hormones. The lungfish decapeptide (ANG
      I) induced dose-dependent increases in arterial pressure in the rat. The lungfish
      octapeptide (ANG II) released aldosterone from kidney-adrenal tissue in vitro in
      a dose-dependent manner and induced dose-dependent increases in arterial pressure
      of the lungfish. Substitution of asparagine with aspartic acid in the first
      position (tetrapod-type ANG II) did not alter the blood pressure response
      significantly, but a second substitution of the valine in the (5)-position with
      isoleucine (ANG II form found in human and rat) abolished the rise in arterial
      pressure in lungfish over the same dose range.

PMID- 10208770
TI  - Prenatal development of hematopoietic and hormone-producing cells in the chicken
      adenohypophysis.
AB  - The developmental sequence of markers for hematopoietic, hormone-producing, and
      folliculo-stellate cells in the chicken adenohypophysis is described using
      immunohistochemical staining techniques. Hematopoietic cells are detected in
      cryosections of the adenohypophysis starting from 10- or 12-day embryos, using
      chicken-specific monoclonal antibodies against the leukocyte common antigen
      (CD45) and the macrophage antigen CVI-ChNL-68.1, respectively. During the second
      half of embryonic development, CVI-ChNL-68.1-positive macrophages, which are also
      found in several lymphoid and nonlymphoid tissues of the embryo, progressively
      populate the adenohypophysis, simultaneously with the maturation of the different
      hormone-producing cell types in their characteristic topographical location. In
      cryosections of embryonic chicken adenohypophyses, from day 10, distinct cell
      populations gradually become immunoreactive to chicken-specific monoclonal
      antibodies against proopiomelanocortin, the beta-subunit of luteinizing hormone,
      growth hormone, and prolactin. At hatching, these pituitary hormones are
      immunohistochemically detectable in a topographical pattern corresponding to the
      known distribution of hormone-producing cells in the adult chicken
      adenohypophysis. However, in the hatchling, there is no immunoreactivity to the
      S100 protein, a marker characteristic for the non-hormone-producing folliculo
      stellate (FS) cells in the adult adenohypophysis, although FS cells in the 4-week
      old chicken show a strong immunoreactivity to a polyclonal antiserum against
      bovine S100. Immunoreactivity to the major histocompatibility complex class II
      (MHC-class II of the chicken) is also absent in the embryonic adenohypophysis,
      thereby corroborating the absence of these characteristic markers of dendritic
      cells (MHC class II) and FS cells (S100) in the perinatal adenohypophysis, as in
      the rat. It is concluded that, whereas early macrophages populate the
      adenohypophysis simultaneously with the maturation of hormone-producing cells
      (i.e., during the second half of embryonic development), the FS cell-specific
      expression of S100 protein does not take place before hatching, and neither does
      the expression of MHC-class II antigens in the embryonic chicken adenohypophysis.

PMID- 10208771
TI  - Humoral regulation of hemoglobin transition from larval to adult types in a
      salamander, Hynobius retardatus.
AB  - In amphibians hemoglobin (Hb) transition from larval to adult types occurs during
      metamorphosis. Hemoglobin transition in the salamander Hynobius retardatus also
      occurs during metamorphosis, but depends on activity of the pituitary gland,
      rather than that of the thyroid gland. These findings were supported by the fact
      that the transplanted pituitary gland to hypophysectomized (Hx) larvae exerted
      accelerating effects on Hb transition. Contrary to this, a homogenate of the
      pituitary gland from Xenopus laevis had no accelerating effect on Hb transition
      when injected into Hx larvae of H. retardatus. Whereas exogeneously applied
      triiodothyronine (T3) or a combination of T3 and hydrocortisone had an
      accelerating effect on Hb transition in the Hx larvae, a single treatment with
      hydrocortisone in the Hx larvae had no effect. When an inhibitor of synthesis of
      adrenocortico-steroid hormones, metyrapone, was applied in combination with
      goitrogens to intact larvae, Hb transition from larval to adult types was
      suppressed compared with normal controls, suggesting that the thyroid-corticoid
      system is involved in Hb transition. These results suggest that Hb transition in
      H. retardatus is controlled by two independent accelerating factors, from both
      the pituitary gland and the thyroid-corticoid system. These control mechanisms
      are different from the general regulation of metamorphosis that occurs in many
      amphibians. A tentative model of hormonal controls in Hb transition from larval
      to adult types during the metamorphosis in H. retardatus is presented.

PMID- 10208772
TI  - Steroid levels and steroid metabolism in relation to early gonadal development in
      the tilapia Oreochromis niloticus (Teleostei: cyprinoidei).
AB  - Sex steroid levels and steroid metabolism were investigated in relation to early
      gonadal development in a mixed sex population of the tilapia Oreochromis
      niloticus. Androstenedione (AD), testosterone (T), 11-ketotestosterone (KT), and
      estradiol (E2) were quantified by radioimmunoassay (RIA) of whole body extracts.
      Androstenedione metabolism was assessed by incubations in vitro with 3H-AD and
      metabolites were identified by thin-layer chromatography coupled with
      radioisotope image analysis. Histology revealed the presence of gonadal
      structures at 15 days postfertilization (dpf) and ovaries at 36 dpf, with other
      individuals exhibiting undifferentiated gonads containing germinal cells,
      presumably eventual testes. Androgen levels were initially high in eggs then
      decreased severalfold prior to the emergence of gonads. A transient increase in
      the levels of T and KT occurred at 22 dpf. Levels of E2 were either low or
      undetectable except for a transient increase (43 dpf) after ovaries were present.
      Levels of T approached bimodality from 57 to 64 dpf. Steroid metabolism generally
      increased throughout development. Metabolites were generally similar, consisting
      of T predominantly as well as 5beta-reduced androgen derivatives and 11
      oyxgenated derivatives. Estriol was tentatively identified. Conjugated steroids
      were not formed. Two types of steroid metabolic profiles occurred at 50 dpf.
      These results demonstrate that changes in the steroidogenic profile occur during
      early transitions of gonadal development. Notably, (1) steroid biosynthetic
      capacity preceeds gonadal differentiation, (2) evidence for estrogens occurs
      after ovarian development has begun, and (3) bimodality of levels of T and
      differential steroid metabolism later in development may reflect the onset of
      sexual divergence.

PMID- 10208773
TI  - A homologous radioimmunoassay for the measurement of urotensin II in the
      euryhaline flounder, Platichthys flesus.
AB  - A sensitive and specific homologous radioimmunoassay (RIA) has been developed to
      measure tissue and circulating levels of the fish caudal neurosecretory system
      neuropeptide, urotensin II (UII), in the euryhaline flounder Platichthys flesus.
      A polyclonal antiserum was raised against flounder UII in rabbit; UII-125I was
      produced by the iodogen method and purified by HPLC. Antiserum specificity to
      flounder UII was demonstrated through lack of cross-reactivity with several small
      peptides and parallelism with standard curves for serial dilutions of UII in
      plasma and urophysial extracts. Biological activity of the peptide measured by
      UII RIA was confirmed by bioassay. Plasma intra- and interassay coefficients of
      variation were 9 and 18% (n = 5 and n = 3), respectively, nonspecific binding
      constituted 4.6% (+/-1.42%, n = 8) of total counts, and the limit of RIA
      detectability was estimated as 1.5 x 10(-16) M UII/assay tube. Plasma samples
      were subject to a reversed-phase liquid chromatography purification protocol
      which had an extraction efficiency of 63% (+/-10%, n = 6) and showed consistent
      recovery of UII over a range of plasma volumes and peptide concentrations. Plasma
      UII concentrations in seawater (SW)-adapted flounder (3.80 +/- 0.77 x 10(-11) M,
      n = 7) were significantly higher than those in freshwater (FW)-adapted fish (1.10
      +/- 0.15 x 10(-11) M, n = 7). This variation coincided with differences in plasma
      osmolality and Na+ levels. No differences were found, however, between urophysial
      UII concentrations in SW-adapted (3.71 +/- 1.78 x 10(-10) M UII/gland, n = 7) and
      FW-adapted (2.53 +/- 1.33 x 10(-10) M UII/gland, n = 7) flounder.

PMID- 10208774
TI  - Daily estradiol and progesterone levels relative to laying and onset of
      incubation in canaries.
AB  - Female birds may optimize reproduction by modifying clutch size and the timing
      for the onset of incubation. We measured fecal estradiol-17beta (E) and
      progesterone (P) in laying canaries to better understand how onset of incubation
      might regulate clutch size. Both E and P rose sharply to maxima 1 day before the
      first egg was laid. Thereafter, E steadily declined, but P remained high through
      2 days after the first egg was laid, after which both hormones had returned to
      low levels. Clutch size did not explain variation in E or P output during the
      laying cycle. When analyzed with respect to onset of incubation, E and, to a
      lesser extent, P dropped significantly on the day incubation began, irrespective
      of whether or not females had finished ovulating. We suggest that factors
      initiating incubation also cause the decline in E production by small follicles,
      which in turn may inhibit yolk sequestration in large follicles. Further
      experiments in which onset of incubation is manipulated may reveal the mechanisms
      by which this behavior regulates clutch size and reproductive output.

PMID- 10208775
TI  - Serum prolactin concentrations in the captive female African elephant (Loxodonta
      africana): potential effects of season and steroid hormone interactions.
AB  - Research was conducted to determine whether seasonal changes in prolactin
      secretion occur in nonpregnant female African elephants and to examine potential
      functional interrelationships between secretion of prolactin, cortisol, and
      progesterone. Weekly blood samples were taken for 18 months from four female
      African elephants and the sera were analyzed by RIA for progesterone, cortisol,
      and prolactin concentrations. There was no significant effect of season on serum
      concentrations of prolactin. Estrous cycles averaged 14 weeks in length and were
      composed of a 9-week luteal phase and a 5-week follicular phase (based on
      progesterone concentrations consistently >200 and <200 pg/ml, respectively).
      Estrous cycle synchronicity was evident between pairs of elephants. Serum
      concentrations of prolactin (3.91 +/- 0.69 ng/ml; range: 0.84-15.8 ng/ml) were
      significantly lower during the luteal, compared with the follicular, phase (P <
      0.0001; t test) and were positively correlated with serum concentrations of
      cortisol (r = 0.14; P < 0.05). Mean (+/-SE) serum concentration of cortisol was
      5.7 +/- 1.3 ng/ml (range: 1.4-19.3 ng/ml), and concentrations of this adrenal
      steroid were negatively correlated with progesterone concentrations (r = -0.15; P
      < 0.01). Increased serum concentrations of prolactin detected during the
      follicular phase suggest that this hormone may be regulated by ovarian estrogens
      and may play a role in modulating ovarian function in the elephant.

PMID- 10208776
TI  - Endocrine patterns during aging in the common tern (Sterna hirundo).
AB  - Blood samples were taken from breeding common terns (Sterna hirundo) of known age
      during two successive breeding seasons to determine if plasma concentrations of
      estradiol, progesterone, androgen, and luteinizing hormone (LH) reflect the
      process of aging. Males and females were trapped and sampled once between laying
      of the first and the second eggs in the clutch. The transient capture and
      sampling did not disrupt incubation or the timing of the subsequent oviposition.
      Ages ranged from 2 to 21 years, with most in the range 4-11 years. There was a
      strong inverse correlation (P < 0.0001) between age and laying date in both
      females and males, with older birds nesting earlier in the season. Plasma LH
      levels increased (P < 0.005) among mature (>5 year) females. Plasma progesterone
      and E2 were positively correlated with each other among mature females, but did
      not change in an age-dependent manner. In males, plasma progesterone levels
      showed no age-related changes. However, maturing (3-5 year) males showed
      increasing plasma androgen levels (P < 0.01); mature males showed no change with
      age. Plasma LH levels were correlated with androgen levels in both maturing and
      mature males. Plasma progesterone declined with age in maturing males (P <
      0.001). These data provide evidence for changing endocrine status with age, but
      the patterns differ for younger individuals (</=5 year) and mature birds. It
      appears that in younger individuals, nesting experience and maturity of the pair
      affect reproductive performance and endocrine status. Individual variability was
      high for all hormones, possibly masking age-related changes. Only breeding
      individuals were sampled at all ages, although the proportion of the population
      that continues to reproduce may decline as the birds age. In summary, common
      terns continue to breed successfully until at least age 21 years and these
      individuals maintain relatively stable endocrine status during aging. Although
      there was some indication of declines in estradiol and androgens among the oldest
      birds (16-21 years), these declines were not statistically significant and were
      manifested in only a small fraction (<4%) of the breeding population.

PMID- 10208777
TI  - Somatostatin in the ovary of an African lungfish (Protopterus annectens): an in
      situ hybridisation, immunohistochemical, and autoradiographical study.
AB  - In mammals, somatostatin seems to be involved in the control of ovarian
      steroidogenesis. There have been no studies on the presence or actions of
      somatostatin in the ovary of nonmammalian vertebrates. The localisation of
      somatostatin-14 was examined immunohistochemically using the antibody to
      somatostatin-14 in the ovary of the African lungfish Protopterus annectens.
      Immunoreactivity was present in the granulosa cells of mature ovarian follicle
      examined by light microscopy. Using an oligonucleotide probe complementary to
      mRNA for somatostatin-14 and labelled at the 3'-end with alpha-35S, in situ
      hybridisation demonstrated somatostatin-14 mRNA distributed in cells showing the
      same localisation as that of the immunoreactive cells. Binding sites for SST-14
      were identified with autoradiography using [125I]somatostatin-14. Binding sites
      were localised on granulosa and theca cells. Somatostatin-14 may be thus
      synthesised in the lungfish ovary.

PMID- 10208778
TI  - Properties of the melatonin-generating system of the sailfin molly, Poecilia
      velifera.
AB  - The properties of the melatonin-generating system of a tropical teleost, the
      sailfin molly (Poecilia velifera), were investigated in vitro in a series of
      experiments using static or perifusion culture techniques. The properties
      examined included photic entrainment, circadian rhythmicity under continuous
      light (LL) and continuous darkness (DD), functionality of the melatonin
      generating system at birth, and presence of multiple circadian oscillators in the
      molly pineal. Pineal glands or skull caps with the pineal gland firmly attached
      were dissected from adult and new-born fishes, respectively, and placed into
      static or perifusion culture at constant temperature (27 degrees C) depending
      upon the experiment. Melatonin release in samples was quantified by RIA. Rhythmic
      melatonin release was observed from isolated adult pineals under 12L:12D and
      14L:10D, with low amounts of melatonin released during the light and high amounts
      during the dark. Melatonin release was inhibited by LL. However, under DD,
      melatonin release was robust and rhythmic with a circadian period (Tau) that
      ranged between 21.3 and 27.0 h (n = 21). Pineals from new-born (1-day old)
      mollies released melatonin rhythmically under a light:dark cycle and DD in both
      static and perifusion culture. Melatonin release from half and quarter pineals of
      adult mollies under DD was robust and rhythmic with circadian periods that ranged
      between 22.5 and 29.0 h (n = 19). Taken together, these data show that the molly
      pineal is photosensitive, fully functional from birth, and contains multiple
      circadian oscillators (at least four) regulating melatonin production.

PMID- 10208779
TI  - Presence of an intrapineal circadian oscillator in the teleostean family
      Poeciliidae.
AB  - In most fish, rhythmic melatonin production is controlled by circadian
      oscillators located within the pineal (=pineal clocks) that are reset daily by
      the ambient light:dark (LD) cycle. However, one question that has yet to be
      addressed concerns the phylogenetic distribution of the pineal clock within fish
      families. We tested whether a pineal clock identified in the sailfin molly
      (Poecilia velifera) in an earlier study is also present in some other
      representatives of the teleostean family Poeciliidae. Isolated pineals from
      adults belonging to the genus Poecilia (P. velifera albino, P. reticulata, and P.
      sphenops), genus Xiphophorus (X. helleri and X. maculatus), and genus Limia (L.
      vittata) were obtained and cultured under LD and/or continuous darkness (DD) at
      constant temperature (27 degrees C). With one exception, free-running rhythms in
      melatonin release with circadian periodicities ranging from 19.5 to 27.4 h (n =
      26) were detected in isolated pineals from all poeciliid representatives tested
      under DD exposure. In addition, rhythmic melatonin production was also observed
      in isolated pineals of some representatives tested from all three genera under LD
      exposure, suggesting the property of direct photosensitivity. Taken together,
      these data suggest that a circadian oscillator residing in the pineal of the
      sailfin molly also appears to be present in all of the poeciliid representatives
      tested in our system, supporting the notion that the presence of a pineal clock
      occurs at the family level of taxonomic organization.

PMID- 10208781
TI  - Dilated cardiomyopathy in the acquired immunodeficiency syndrome.

PMID- 10208782
TI  - 'There is a voice that I enshrine in my heart...'.

PMID- 10208783
TI  - Estimation of walking distance in intermittent claudication: need for
      standardization.

PMID- 10208784
TI  - Reduction of myocardial damage by prolonged treatment with subcutaneous low
      molecular weight heparin in unstable coronary artery disease. FRISC study group.
      Fragmin during Instability in Coronary Artery Disease.
AB  - AIMS: Several studies have proved heparin useful in treating patients with
      unstable coronary artery disease. The present study investigates whether
      Selvester QRS scoring for estimation of myocardial infarct size increases the
      incidence of detection of acute myocardial infarction during follow-up in a trial
      of patients with unstable angina/non-Q wave myocardial infarction treated with
      low molecular weight heparin or placebo. Finally it will be discussed how the QRS
      score, used for end-point identification, impacts on the power calculation in
      clinical trials. METHODS AND RESULTS: Electrocardiographic data on 1276 patients
      (644 in the placebo group, 632 in the low molecular weight heparin treatment
      group) were available. All ECGs were scored according to the Selvester QRS
      scoring method. At 40 days, more patients in the placebo than in the heparin
      group had achieved a threshold level of QRS score (25.9% vs 21.1%, P=0.05).
      Myocardial infarction, diagnosed as per the classic Q wave criteria, occurred in
      3.7% of patients in the placebo group and in 0.9% in the low molecular weight
      heparin group at 6 days (P=0.002). At 40 days, the rates were 8.2% (placebo) and
      5.7% (low molecular weight heparin, P=0.2). By combining the classic criteria
      with the Selvester method the myocardial infarction end-point rate in both groups
      was almost doubled (8.2% to 14.4% in the placebo group and 5.7% to 11.1% in the
      low molecular weight heparin group, P=0.07). The 216 patients with non-evaluable
      electrocardiograms did not differ from the 1276 patients as regards baseline
      characteristics; however, they had a significantly poorer prognosis, with a
      death/myocardial infarction rate of 20% at 40 days, compared with 8% among the
      patients with evaluable electrocardiograms (P<0.00001). CONCLUSION: Long-term
      subcutaneous treatment with low molecular weight heparin decreases the number of
      subsequent myocardial infarctions - determined both conventionally and by an
      increase in QRS score - in patients with unstable coronary artery disease. Silent
      myocardial infarctions detected by QRS score, as well as clinical myocardial
      infarctions, could be used as end-points in clinical trials of ischaemic heart
      disease and thus lower the population needed for obtaining statistical power.

PMID- 10208785
TI  - Quality of life after coronary angioplasty or bypass surgery. 1-year follow-up in
      the Coronary Angioplasty versus Bypass Revascularization investigation (CABRI)
      trial.
AB  - BACKGROUND: Coronary artery bypass grafting (CABG) and percutaneous transluminal
      coronary angioplasty (PTCA) have both been shown to be safe and effective in the
      treatment of coronary artery disease. Nine randomized studies comparing CABG and
      PTCA have delivered consistent results, with no significant differences in
      mortality between the methods, either in single or in multivessel coronary artery
      disease. An important outcome measurement after intervention is the patient's
      subjective appraisal of the intervention. Results from the CABRI substudy on
      quality of life at 1 year follow-up are presented in this report. METHODS: CABRI
      is a multicentre, randomized, open comparison of patients assigned to either PTCA
      or CABG. Patients were recruited from 26 high volume European hospitals over a 53
      month period starting in July 1988. A quality of life substudy was also set up,
      but participation was optional. Seven out of 26 centres took part in the study.
      One hundred and fifty-four (14.6%) out of the 1054 main study patients
      participated. Perceived health status was assessed at baseline and 1 year after
      revascularization by means of The Nottingham Health Profile and a set of 12 other
      questions. RESULTS: A significant improvement in quality of life in terms of the
      total score and in the Nottingham Health Profile for both groups, as compared
      with baseline, was found. A trend towards better outcome concerning energy was
      found favouring CABG. This trend might be due to the fact that the CABRI protocol
      permitted incomplete revascularization in the PTCA arm and did not exclude
      patients with totally occluded vessels. When adjusted for baseline differences,
      no difference in health-related quality of life at follow-up was found between
      the sexes, or between the PTCA and the CABG groups. A significant correlation was
      found between improvement in quality of life and severity of angina when adjusted
      for baseline values. CONCLUSIONS: This study has shown that there is no general
      difference in health-related quality of life 1 year after bypass surgery or
      angioplasty; however, data presented are suggestive of a more favourable outcome
      in degree of perceived energy in the bypass group.

PMID- 10208786
TI  - A randomized comparison of intra-aortic balloon pumping after primary coronary
      angioplasty in high risk patients with acute myocardial infarction.
AB  - AIMS: Intra-aortic balloon pumping reduces afterload and may be effective in
      improving reperfusion in high risk infarct patients treated with primary
      angioplasty. METHODS: High risk infarct patients referred from other centres for
      primary PTCA were randomized to treatment with or without an intra-aortic balloon
      pump. The primary end-point consisted of the combination of death, non-fatal
      reinfarction, stroke or an ejection fraction <30% at the 6 month follow-up. A
      weighted unsatisfactory outcome score (as previously described by Braunwald),
      enzymatic infarct size and left ventricular ejection fraction were secondary end
      points. RESULTS: During a 3.5 year period, 238 patients were randomized, 118 to
      intra-aortic balloon pump therapy and 120 to no intra-aortic balloon pump
      therapy. Cross-over (25% in the intra-aortic balloon pump group and 31% in the no
      intra-aortic balloon pump group) occurred in both treatment arms. The primary end
      point was reached in 31 (26%) patients assigned to an intra-aortic balloon pump
      and in 31 (26%) assigned to no intra-aortic balloon pump (P=0.94). Enzymatic
      infarct size (LDHQ72) was calculated in 163 (68%) patients and was not
      significantly different between either group (intra-aortic balloon pump: 1616+/
      1148, no intra-aortic balloon pump: 1608+/-1163). The left ventricular ejection
      fraction was measured at the 6 month follow-up in 168 patients (80% of patients
      alive). No difference in ejection fraction was found in either group (intra
      aortic balloon pump: 42+/-13%, no intra-aortic balloon pump: 40+/-14%, P=0.51).
      Major complications occurred in 8% of patients treated with an intra-aortic
      balloon pump. CONCLUSIONS: Systematic use of intra-aortic balloon pumping after
      primary angioplasty does not lead to myocardial salvage or to a better clinical
      outcome in high-risk infarct patients. Use of intra-aortic balloon pumping after
      primary PTCA for acute myocardial infarction should be reserved for patients with
      severe haemodynamic compromise.

PMID- 10208787
TI  - Differences in drug treatment of chronic heart failure between European
      countries.
AB  - AIMS: A large number of drugs are currently used for the treatment of chronic
      heart failure. Treatment for other cardiovascular disorders has been shown to
      differ between countries. In this study we examined whether this would also be
      true in heart failure. METHODS AND RESULTS: We studied patients with moderate to
      severe heart failure, who were enrolled in an international survival study, and
      compared patterns of drug use between the nine countries that each included >50
      patients in the study. The results were analysed to determine whether observed
      differences between countries could be explained by differences in the patients
      recruited. 1825 patients were studied (range 81-427 per country). By trial
      protocol, most patients were treated with angiotensin converting enzyme (ACE)
      inhibitors (92%) and all with diuretics, but the proportion of patients taking
      high doses of these drugs was markedly different between countries. Large
      differences were also observed in the use of digoxin (overall 64%, 39% in the
      U.K. to 87% in Germany) and antiarrhythmics (overall 25%, with the highest use
      44% in France). The use of beta-blockers and calcium antagonists was low (overall
      6% and 8%, respectively), but also different between countries. Anticoagulants
      (overall 43%) were used in many patients in the Netherlands and Switzerland
      (around 70%), while antiplatelets (overall use 30%) were most often prescribed in
      Denmark (51%). CONCLUSIONS: Large differences in drug use and dosing for patients
      with advanced heart failure are observed between (European) countries. None of
      these differences could be explained by differences in patient characteristics,
      and whether they are related to factors such as tradition, economic circumstances
      and national guidelines, etc. is unknown.

PMID- 10208788
TI  - Effects of education and support on self-care and resource utilization in
      patients with heart failure.
AB  - AIMS: To test the effect of education and support by a nurse on self-care and
      resource utilization in patients with heart failure. METHODS: A total of 179
      patients (mean age 73, 58% male, NYHA III-IV) hospitalized with heart failure
      were evaluated prospectively. Patients were randomized to the study intervention
      or to 'care as usual'. The supportive educative intervention consisted of
      intensive, systematic and planned education by a study nurse about the
      consequences of heart failure in daily life, using a standard nursing care plan
      developed by the researchers for older patients with heart failure. Education and
      support took place during the hospital stay and at a home visit within a week of
      discharge. Data were collected on self-care abilities, self-care behaviour,
      readmissions, visits to the emergency heart centre and use of other health care
      resources. RESULTS: Education and support from a nurse in a hospital setting and
      at home significantly increases self-care behaviour in patients with heart
      failure. Patients from both the intervention and the control group increased
      their self-care behaviour within 1 month of discharge, but the increase in the
      intervention group was significantly more after 1 month. Although self-care
      behaviour in both groups decreased during the following 8 months, the increase
      from baseline remained statistically significant in the intervention group, but
      not in the control group. No significant effects on resource utilization were
      found. CONCLUSIONS: Intensive, systematic, tailored and planned education and
      support by a nurse results in an increase in patients' self-care behaviour. No
      significant effects were found on use of health care resources. Additional
      organisational changes, such as longer follow-up and the availability of a heart
      failure specialist would probably enhance the effects of education and support.

PMID- 10208789
TI  - Cytokines and neurohormones relating to body composition alterations in the
      wasting syndrome of chronic heart failure.
AB  - BACKGROUND: Chronic heart failure is one of a number of disorders associated with
      the development of a wasting syndrome. The precise mechanisms of this remain
      unknown, but previous studies have suggested a role for immune and neurohormonal
      factors. METHODS: We aimed to investigate in detail the differences in body
      composition (dual X-ray absorptiometry) and the relationship to candidate
      biochemical factors of the immune, neurohormonal and metabolic systems in 15
      healthy controls, 36 stable non-cachectic and 18 cachectic patients with chronic
      heart failure. RESULTS: Non-cachectic patients showed reduced leg lean tissue (
      9.1%, P<0.01) compared to controls. Cachectic patients had significantly reduced
      lean (-21.0% vs controls, -19.9% vs non-cachectics), fat (-33.0% vs controls, 
      37. 0% vs non-cachectics) and bone tissue (-17.5% vs controls, -15.9% vs non
      cachectics) (all P<0.0001). Cachectic patients showed a significantly increased
      cortisol/dehydroepiandrosterone ratio (+203% vs controls, P<0.0001; +89% vs non
      cachectics, P=0.0011) and increased cytokine levels (TNF-alpha, soluble TNF
      receptor 1, interleukin-6). The levels of catabolic hormones and cytokines
      correlated significantly with reduced muscle and fat tissue content and reduced
      bone mass. CONCLUSION: Peripheral loss of muscle tissue is a general finding in
      chronic heart failure. The wasting in cardiac cachexia affects all tissue
      compartments and is significantly related to neurohormonal and immunological
      abnormalities.

PMID- 10208790
TI  - Prevalence and natural course of ectopic atrial tachycardia.
AB  - AIMS: The purpose of this study was to calculate the prevalence of ectopic atrial
      tachycardia in a population of young asymptomatic males and to assess its natural
      course both in asymptomatic subjects and in symptomatic hospital patients.
      METHODS AND RESULTS: 12-lead electrocardiograms (ECG) of 3554 consecutive males
      applying for a pilot's licence were analysed. ECGs of symptomatic arrhythmia
      patients at two university hospitals were also analysed. A repeat ECG was taken
      in cases of ectopic atrial tachycardia to assess the natural course of this
      arrhythmia. Twelve out of 3554 asymptomatic subjects (prevalence 0.34%) and 17
      out of 3700 symptomatic arrhythmia patients (prevalence 0.46%) had ECG evidence
      of ectopic atrial tachycardia. A repeat ECG was obtained after a mean follow-up
      of 8+/-3 years in asymptomatic subjects and 7+/-3 years in symptomatic patients.
      After the follow-up, seven (26%) out of 27 patients were still in a similar
      ectopic atrial rhythm, 10 (37%) showed a change in P wave morphology and 10 (37%)
      were in sinus rhythm. Heart rate was significantly slower (mean rate 81+/-19 vs
      109+/-17 beats. min-1) in the repeat ECGs. CONCLUSION: Asymptomatic ectopic
      atrial tachycardia is not an uncommon finding in a population of young males. The
      majority of patients show slowing of heart rate in the course of time, either
      with restoration of sinus rhythm or with a change in P wave morphology,
      suggesting that the ectopic foci undergo gradual degeneration with time.

PMID- 10208791
TI  - Hand specialization, sympatry, and mixed-species associations in callitrichines.
AB  - Hand morphology in callitrichines (i.e., tamarins, marmosets, and Goeldi's
      monkey) is correlated with positional and foraging behaviors. This study examines
      hand shape in callitrichines using an allometric approach. It addresses a series
      of questions relating hand anatomy, insect foraging behavior, and resource
      partitioning in callitrichines. The main questions are: 1. Do the hands of
      Leontopithecus differ in shape from all other callitrichine taxa allowing it to
      perform highly manipulative prey foraging behaviors? 2. Are the hands of Saguinus
      fuscicollis adapted to manipulative foraging, and are they functionally similar
      to Leontopithecus' hands? 3. Is hand morphology in S. fuscicollis more similar to
      the hand morphology of sympatric tamarin species with whom it does not form mixed
      species troops (S. nigricollis and S. tripartitus) than to those sympatric
      tamarin species with whom it does form mixed troops (S. mystax, S. labiatus, and
      S. imperator)? Measurements of hand length (HL), width (HW), and thickness (HT)
      were taken from 1350 museum specimens of callitrichines (Callithrix, Cebuella,
      Leontopithecus, Saguinus, and Callimico), squirrel monkeys (Saimiri), and owl
      monkeys (Aotus). The analysis indicates that hand shape covaries with foraging
      strategy. Specifically, the hands of Leontopithecus are adapted for manipulative
      foraging and are relatively longer and more slender than the hands of other
      callitrichines. A similar pattern is observed in the hands of S. fuscicollis, S.
      tripartitus and S. nigricollis. These latter species, however, differ
      significantly in shape from all other tamarin species. Large differences in hand
      morphology are observed among tamarin species that form mixed-species troops.
      These anatomical differences may permit resource partitioning and coexistence
      among these closely related taxa. Hand shape, expressed as log HLGM (logged hand
      length divided by the geometric mean of all measurements), is a good predictor of
      manipulative and non-manipulative prey foraging techniques employed by
      callitrichines.

PMID- 10208792
TI  - Patterns of sexual dimorphism in the hominoid distal humerus.
AB  - Basic biomechanical principles predict that body size differences and differences
      in the positional behavior of primates should impact on the design of the
      locomotor skeleton. Allometric distortions in joint shape might be expected
      between sexes if the degree of body size dimorphism is substantial and/or if sex
      specific differences exist in behavior. Nevertheless, there are few documented
      cases of sexual dimorphism in the limb joints of hominoids, despite substantial
      body size dimorphism and some reports of intersexual differences in positional
      behavior. This study re-examines sexual dimorphism in the hominoid distal humerus
      using coordinate data, and distinguishes explicitly between degree of dimorphism
      (i.e., the magnitude of intersexual differences) and pattern of dimorphism (i.e.
      , the nature of these differences). Using a variety of multivariate morphometric
      methods (e.g., canonical variates analysis of Mosimann shape variables; Euclidean
      Distance Matrix Analysis of both form and pattern difference matrices), we
      address the following issues: (1) do males and females of different species and
      subspecies (or ethnic groups for humans) maintain similar joint shapes? (2) are
      multiple patterns of dimorphism evident in this region of hominoids? (3) are
      differences and similarities in degree and pattern predicted by phylogenetic
      propinquity and positional behavior? For the most part, our results support
      earlier findings that sexual dimorphism in the shape of the anthropoid elbow is
      slight. Of the eight taxa considered here, only the western lowland gorillas
      exhibited significant differences in the shape of the distal humerus. Gorilla
      gorilla gorilla also displays a significantly different pattern of dimorphism
      from the orang-utan. Pattern differences between Andaman Islanders and both
      mountain gorillas and the orang-utan also approach statistical significance
      (P<0.06 and P<0.08, respectively). Overall, and despite marked differences in the
      degree of dimorphism, the knuckle-walking African apes are more similar in
      patterns of dimorphism to each other than to other taxa (e.g., gorillas are more
      similar to orang-utans in degree, but more similar to chimpanzees and bonobos in
      pattern). We could find no definitive "human pattern" in our results and suspect
      that this is because human upper limbs face less stringent mechanical constraints
      since they are relieved of locomotor stresses (but we cannot rule out the
      possibility of undocumented differences among our human groups in sex-specific,
      work-related activities). We anticipate finding additional pattern differences
      among anthropoids in articular dimorphism as we add other taxa to our sample
      (including fossil hominids), and examine other joint systems.

PMID- 10208793
TI  - The challenge of pollen analysis in palaeoenvironmental studies of hominid beds:
      the record from Sterkfontein caves.
AB  - The search for pollen in carbonate-rich sediments from the hominid site
      Sterkfontein has been justified because previous investigations suggested that
      although pollen contamination is a problem, speleothems (e.g. travertines and
      stalagmites) are most likely to contain reliable assemblages. The new results
      confirm that, although they have some potential, most sediment types from the
      site, even speleothems, are usually not suitable for analysis and that they
      contain very low concentrations of pollen, if any. The extraction of pollen from
      them is complicated by the problem of contamination from the modern environment.
      Such contamination has shown up in many previous investigations at this and
      similar sites and judging from published literature, its significance has not
      been fully appreciated. Cave palynology can be a very valuable tool in
      palaeoenvironmental research but the caveats associated with palynology of
      different sediment types especially carbonate impregnated sediments must be
      emphasized.

PMID- 10208794
TI  - Recognizing species diversity among large-bodied hominoids: a simulation test
      using missing data finite mixture analysis.
AB  - A persistent problem in paleoanthropology is the recognition of intra- vs. inter
      specific differences within fossil samples. Exacerbating this situation is the
      often fragmentary nature of the fossils themselves, thus precluding rote
      applications of many multivariate approaches designed for complete case analyses.
      In this paper we apply finite mixture analysis to samples of large-bodied
      hominoids to test this procedure's efficacy in clustering individuals by species
      without a priori knowledge of group membership. In addition, we stochastically
      remove individual specimens and measurements, simulating small, incomplete fossil
      samples, and re-apply the finite mixture procedure to test how often it correctly
      assigns these "fragmentary" specimens. Finite mixture analysis can be highly
      accurate, even when confronted with small sample sizes and missing data. For
      example, a combination of 124 chimpanzees and humans are correctly identified in
      one analysis, and the accuracy drops only 2% to become 98% when the total sample
      size is reduced to 16 and missing data patterns are applied. In comparisons to
      better known methods that have been used to recognize groups in the fossil
      record, such as k-means, the benefits of finite mixture analysis are readily
      apparent. First, k-means is unable to accommodate missing data, an obvious
      deficiency when investigating the fossil record. Second, in direct comparisons of
      their ability to accurately assign "unknowns" to taxa, finite mixture performed
      at least as well as, and often better than, k-means in our analyses. A potential
      test that can be used to identify species in the fossil record, derived from
      comparisons of results generated from a general vs. a restricted (isometry
      corrected) finite mixture analysis, is presented.

PMID- 10208795
TI  - Statistics of sexual size dimorphism.
AB  - In comparative studies of sexual size dimorphism (SSD), the methods used to
      quantify dimorphism are controversial. SSD is commonly expressed as a ratio
      between species mean values of males and females, such as M/F or (M-F)/([M+F]/2),
      but a number of investigators have suggested that ratios should not be used,
      mainly because their distributions usually violate the assumptions of parametric
      statistical tests, or because they lead to spurious relationships that invalidate
      the interpretation and statistical significance of regressions and correlations.
      As an alternative to ratios, the comparative study of SSD can be conducted by a
      combination of regression with sex-specific data and residuals from this
      regression. Twenty-five data sets were selected from the literature and used to
      duplicate a variety of statistical procedures commonly employed in studies of
      SSD. All analyses were repeated with five different ratios and with methods that
      avoid the calculation of any ratios. These data and a review of the statistical
      properties of ratios and residuals indicate that: (1) most of the ratios used in
      the SSD literature are unnecessary, and several commonly used ratios are
      statistically inferior to others. Only two ratios are needed, one on a
      logarithmic scale and one on a linear scale; (2) there is no problem with
      spurious correlation or non-normality when ratios are used in several types of
      statistical procedures commonly employed in studies of SSD; (3) residuals cannot
      replace ratios for the evaluation of many questions regarding the pattern of SSD
      among species; and (4) residuals usually are used incorrectly, leading to
      misspecified regression equations. Most of the questions for which residuals are
      used should be addressed by multiple regression. These results apply to studies
      using comparative methods with or without adjustments for phylogenetic effects.

PMID- 10208796
TI  - Resolution regarding the transport of hominid fossils beyond the country of
      origin. International Association for the Study of Human Paleontology.

PMID- 10208798
TI  - A PCR assay for discriminating Neisseria gonorrhoeaebeta-lactamase-producing
      plasmids.
AB  - Oligonucleotide primers were developed for use in polymerase chain reaction (PCR)
      assays to differentiate three related, epidemic beta-lactamase-producing plasmids
      of Neisseria gonorrhoeae-the Asia-(7426 bp), Africa-(5599 bp) and Toronto-(5154
      bp) type plasmids. One-hundred and two N. gonorrhoeae isolates with different
      plasmid profiles were tested-16 isolates carried the Asia plasmid, 41 isolates
      contained the Africa plasmid, 16 isolates contained the Toronto plasmid and 29
      isolates contained no beta-lactamase-producing plasmids. Most (101/102) isolates
      also carried the gonococcal cryptic plasmid, while 27/102 and 44/102 isolates
      carried either the transfer plasmid or the tet M-containing plasmids,
      respectively. The assay was 100% sensitive and specific for identifying the
      correct plasmid type. This assay is useful for rapidly detecting the presence of
      gonococcal beta-lactamase-producing plasmids in clinical samples and
      discriminating them for epidemiological typing.

PMID- 10208797
TI  - Solid-phase sequence scanning for drug resistance detection in tuberculosis.
AB  - DNA chip arrays hold considerable promise for diagnostic sequencing of polymerase
      chain reaction (PCR) products. To date, however, arrays have been relatively
      expensive, complex to use and difficult to interpret, preventing their adaptation
      to the clinical lab. A moderate density array method has been developed that
      enables efficient, easy-to-interpret and robust solid-phase PCR product
      sequencing. Here, the results of Mycobacterium tuberculosis rifampin resistance
      mutation detection by primer-extension-based sequence scanning of the rpo B gene
      of M. tuberculosis are presented. Rifampin resistant clinical isolates were
      identified in as little as 1 h post PCR amplification with visual results
      detection.

PMID- 10208799
TI  - Identification of Aeromonas trota (hybridization group 13) by amplification of
      the aerolysin gene using polymerase chain reaction.
AB  - Aeromonas trota is recognized as an important enteropathogen, and its haemolysin
      (aerolysin) is purported to be one of the virulence factors. Rapid detection and
      identification of A. trota is important for early and specific diagnosis of the
      infectious diseases that it causes. Synthetic oligonucleotide primers were used
      in a polymerase chain reaction (PCR) technique to amplify a species-specific
      sequence of the aerA gene, which encodes the aerolysin of A. trota. A DNA
      fragment of 622 bp was amplified from both lysed cells and isolated DNA from A.
      trota. The identity of the amplified 622 bp fragment was confirmed by digestion
      with BamH I restriction endonuclease, which produced the predicted 557 and 65 bp
      fragments. The lower limit for detection of the aerA gene by PCR amplification
      was 10 pg of total DNA or 10-15 cells ml-1. Primer specificity for A. trota was
      determined by the PCR assay with cells of 55 strains of Aeromonas sppincluding
      all of the 14 currently recognized DNA hybridization groups. A strain of
      Aeromonas enteropelogenes that had been reclassified as A. trota was also PCR
      positive. The method described here can be used to detect aerolysin-producing A.
      trota (hybridization group 13) strains from environmental and clinical samples
      without the use of selective media or additional biochemical tests.

PMID- 10208800
TI  - PCR-RFLP analysis of the flagellin sequences for identification of Burkholderia
      pseudomallei and Burkholderia cepacia from clinical isolates.
AB  - The flagellin genes of four Burkholderia pseudomallei and two Burkholderia
      cepacia clinical isolates were studied by a polymerase chain reaction (PCR)-based
      isolation method using the same pair of primers. The PCR-amplification products
      of the isolates showed a single band of about 1.1 kb, which is similar to a type
      II B. cepacia flagellin reported previously. In order to distinguish these two
      species based on the flagellin PCR-amplified products, Pst I and Xho I
      restriction endonuclease analysis was performed. The results suggest that there
      is sufficient diversity within the flagellin sequences of the closely related
      Burkholderia species, B. pseudomallei and B. cepacia, to enable flagellin-type
      identification on the basis of the pattern of restriction fragments. In addition,
      the flagellin gene should be of considerable use as a genetic marker for clinical
      identification of these organisms.

PMID- 10208801
TI  - Development and evaluation of an extra chromosomal DNA-based PCR test for
      diagnosing bovine babesiosis.
AB  - Subclinical infections of bovine babesiosis, caused primarily by Babesia bigemina
      or Babesia bovis are a challenge to current diagnostic methods. In this study,
      the development and evaluation of a PCR test for sensitive and specific detection
      of B. bigemina or B. bovis is described. The target selected for amplification is
      part of the apocytochrome b gene, conserved in both Babesia spp. and located on
      the linear approximately 6.0 kb extra chromosomal DNA. The test was evaluated to
      detect the parasites over a period of 5 (B. bigemina) and 10 months (B. bovis)
      post infection in experimentally infected cattle. Analysis of DNA extracted from
      blood samples drawn from the experimental cattle in a blind study revealed an
      overall sensitivity of 85 and 64% for B. bovis and B. bigemina respectively,
      while the specificity was 97% for B. bovis and 91% for B. bigemina. The test
      results were compared with the recently developed ribosomal DNA-based polymerase
      chain reaction (PCR) test and to the complement fixation test for both Babesia
      spp. The extra chromosomal DNA-based test was 20% more sensitive than that of
      ribosomal DNA-based tests. This test may be a more desirable alternative to the
      currently used, complement fixation test.

PMID- 10208802
TI  - PCR-restriction endonuclease analysis for identification and strain typing of
      Mycobacterium avium subsp. paratuberculosis and Mycobacterium avium subsp. avium
      based on polymorphisms in IS1311.
AB  - Point mutations in the IS 1311 sequences from sheep and cattle strains of
      Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis) and M. avium
      subsp. avium (M. avium) were targeted to develop a polymerase chain reaction
      (PCR) that would be useful in the diagnosis and control of Johne's disease.
      Candidate PCR tests were evaluated for sensitivity, specificity and ease of
      interpretation of the restriction endonuclease analysis (REA) products. One IS
      1311 PCR, amplifying a 608 base pair product, was shown to be suitable when the
      amplified product was digested with Hinf I and Mse I. The PCR detected 50 fg of
      template DNA from M. paratuberculosis strain 316 V, the equivalent of 10
      organisms. The test was evaluated further using purified DNA from M.
      paratuberculosis and M. avium isolates and diagnostic samples including primary
      radiometric cultures. All 89 M. paratuberculosis samples were correctly
      identified and typed according to host species or IS 900 restriction fragment
      length polymorphism (RFLP) type. All 28 isolates of M. avium were also correctly
      identified. A second PCR/REA strategy based on a shorter fragment of IS 1311 was
      developed for formalin-fixed paraffin-embedded tissue samples. It correctly
      differentiated sheep and cattle strains of M. paratuberculosis in 27 tissue
      samples in which acid fast bacilli had been observed in Ziehl Neelsen stains and
      in which sufficient amplified product was present for REA with Hinf I. Both tests
      were specific for M. paratuberculosis when tested against 24 other mycobacterial
      species. These simple and rapid tests can be used on a range of diagnostic
      samples for the confirmation of Johne's disease and will be of benefit in control
      and eradication programmes for this disease.

PMID- 10208803
TI  - Rapid detection of Listeria monocytogenes by a PCR assay specific for an
      aminopeptidase.
AB  - Specific and rapid detection of Listeria monocytogenes is very important with
      regard to food safety since all other species of Listeria appear to be non
      pathogenic to humans. Conventional microbiological detection methods are very
      time consuming. The polymerase chain reaction (PCR) is one of the most promising
      techniques for rapid detection of micro-organisms in food products. We have
      developed a PCR assay, specific for L. monocytogenes, based on the gene encoding
      an aminopeptidase, which previously has not been described for this species. The
      L. monocytogenes aminopeptidase shares strong sequence similarity with
      aminopeptidase C from Streptococcus thermophilous, Lactobacillus lactis,
      Lactobacillus helveticus, and with a cysteine proteinase from Saccharomyces
      cerevisiae. Polymerase chain reaction primers were synthesized based on the DNA
      sequence of the aminopeptidase gene. A 90 bp product was apparent with all L.
      monocytogenes strains tested but not with other species of Listeria or other
      bacterial genera. The PCR assay, which is performed directly from whole bacterial
      cells, does not involve DNA purification and can be conducted in 4 h. It provided
      positive identification of L. monocytogenes in mixed culture.

PMID- 10208804
TI  - Amplification of Proteus mirabilis chromosomal DNA using the polymerase chain
      reaction.
AB  - A Proteus mirabilis-specific polymerase chain reaction (PCR) was developed and
      standardized. The origin of the primers was a recombinant clone that contained P.
      mirabilis-specific Hind III fragment DNA of 3.5-kilobase pairs. Based on the
      sequence data of P. mirabilis recombinant clone, two primers designated MMKAP 1
      and MMKAP 2 were synthesized for use in the PCR. A P. mirabilis-specific 3.5-kb
      pair DNA product was amplified by the primers from 18 strains of P. mirabilis,
      but not from other Protease species and bacteria. The minimum amount of target
      DNA detected by P. mirabilis PCR was 10 fg using ethidium bromide/ultraviolet
      exposure of gels or Southern blot hybridization with a P. mirabilis recombinant
      DNA probe.

PMID- 10208805
TI  - Simple and rapid identification of different species of Mycobacteria by PCR.
AB  - A simple polymerase chain reaction (PCR) assay for rapid identification of
      different species of mycobacteria was developed. This PCR is based on the use of
      conserved sequences to amplify the genome of several mycobacterial species. The
      amplification patterns obtained were specific and reproducible for the species
      tested. In particular, we could identify Mycobacterium tuberculosis and
      Mycobacterium bovis (both produced the same pattern), Mycobacterium avium,
      Mycobacterium kansasii, Mycobacterium xenopi, Mycobacterium chelonae,
      Mycobacterium peregrinum, Mycobacterium fortuitum, Mycobacterium gordonae and
      Mycobacterium smegmatis. Moreover, due to the numerous copies of the target
      sequences present in the genome, the PCR showed a very high level of sensitivity.

PMID- 10208806
TI  - Discrimination of rat-derived Pneumocystis carinii f. sp. Carinii and
      Pneumocystis carinii f. sp. Ratti using the polymerase chain reaction.
AB  - The rat model of Pneumocystis carinii infection is widely used for the study of
      this non-culturable pathogen. Two genetically divergent <<special forms>> of the
      organism have been detected in infected rat lungs, P. carinii formae specialis
      carinii and P. carinii formae specialis ratti, in some cases as a co-infection.
      We have developed a simple and rapid method to analyse rat-derived P. carinii
      samples, based on DNA amplification of a portion of the gene encoding the
      mitochondrial large subunit ribosomal RNA. A pair of oligonucleotide primers were
      designed for each special form of rat-derived P. carinii, the RC primer pair
      amplifying a 137 bp fragment from P. carinii f. sp. carinii DNA and the RR primer
      pair amplifying a 251 bp fragment from P. carinii f. sp. ratti DNA. The
      specificity of the primers was confirmed by sequencing the amplification
      products. The polymerase chain reaction (PCR) technique was consistent with, and
      more sensitive than, the electrophoretic karyotype method. The application of the
      specific PCR technique has implications for future studies on epidemiology, drug
      sensitivity, immunology and molecular biology of rat-derived P. carinii.

PMID- 10208807
TI  - Molecular screening of potential HNPCC patients using a multiplex microsatellite
      PCR system.
AB  - Microsatellite instability (MSI) is a molecular hallmark of the H ereditary N on-
      P olyposis C olorectal C ancer (HNPCC) syndrome occurring in about 80-90% of the
      tumours and also in sporadic tumours of different organs, albeit at lower
      frequency. Highly unstable colorectal tumours (MSI-H) have different
      histopathological features and tend to have a better prognosis compared to
      neoplasms without (MSS) or with low levels of microsatellite instability (MSI-L).
      Since MSI classification allows the identification of potential HNPCC patients
      and might represent a valuable diagnostic parameter an increasing demand for high
      throughput microsatellite analysis will arise. Therefore, we have adapted five
      diagnostic microsatellites, m(odified) ACTC, mBAT26, mD5S107, mD5S406 and
      mD13S153, to allow coamplification. Using this multiplex polymerase chain
      reaction (PCR) system 29 colorectal tumour tissues with known MSI status could be
      unambiguously identified as MSI-H (13 cases) or MSI-L/MSS (16 cases). Highly
      unstable colorectal tumour detection frequency of individual markers reached 77%
      (mD5S406), 85% (mACTC), 85% (mD5S107), 92% (D13S153) and 100% (mBAT26) showing
      similar sensitivity but improved specificity as compared with a microsatellite
      reference panel. In a prospective analysis of 31 colorectal tumours, the
      multiplex PCR system identified five MSI-H cases. Multiplex MSI PCR is a time
      saving and cost-effective method not restricted to specific technical equipment
      and applicable to a variety of microsatellite-based genotyping approaches.

PMID- 10208810
TI  - Analysis of RNA structure and function using site-specific substitution or
      derivatization 

PMID- 10208809
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- 10208811
TI  - Identification of RNA-protein contacts within functional ribonucleoprotein
      complexes by RNA site-specific labeling and UV crosslinking.
AB  - A variety of cellular processes are carried out by highly complex
      ribonucleoprotein (RNP) particles in which multiple RNA-RNA, RNA-protein, and
      protein-protein interactions occur. The spliceosome, which executes the nuclear
      pre-mRNA splicing reaction, is a particularly striking example of a complex RNP,
      containing a minimum of 50 distinct protein components as well as five small
      nuclear RNAs. In order to identify which among the numerous proteins may play
      critical roles in the splicing reaction, we have assembled spliceosomal complexes
      on pre-mRNA containing a single 32P-labeled nucleotide, isolated the complexes by
      gel filtration, and then carried out UV crosslinking. The combination of these
      three methods has allowed the identification of proteins that crosslink to
      critical sequence elements during each stage in spliceosome assembly. These
      methods should be generally applicable to the analysis of RNP complexes assembled
      in vitro.

PMID- 10208812
TI  - Construction of 4-thiouridine site-specifically substituted RNAs for cross
      linking studies.
AB  - Availability of 4-thiouridine (4-thioU)-containing RNAs is the prerequisite for 4
      thioU site-specific cross-linking studies. This paper presents a method for
      constructing such RNAs. A 5'- and a 3'-RNA are synthesized via phage RNA
      polymerase transcription and/or RNase H site-specific cleavage directed by 2'-O
      methyl-RNA-DNA chimeras. These two half-RNAs in combination correspond to the
      sequence of full-length RNA, with a single nucleotide gap at the junction that
      will be filled in with a 4-thiouridylate. A single p4SUp, which is derived from
      4SUpN (N can be any nucleotide) via 5'-phosphorylation (therefore, the phosphate
      can be radioactive) followed by RNase A digestion, is then ligated to the 3' end
      of the 5'-half RNA with T4 RNA ligase. The 3'-phosphate of the ligated product is
      subsequently removed by calf intestinal alkaline phosphatase to produce a 3'
      hydroxyl group. The resulting 5'-half RNA and the 3'-half RNA with a 5'-phosphate
      group (which can also be radioactive) are then aligned with a bridging
      deoxyoligonucleotide and ligated with T4 DNA ligase. This method was previously
      applied to the P120 pre-mRNA that contains an AT-AC intron, yielding three RNAs
      each containing a single 4-thioU near the 5'-splice site. Subsequent cross
      linking studies with these RNAs yielded detailed information regarding
      interactions between the 5'-splice site and other spliceosomal snRNAs and between
      the 5'-splice site and proteins during splicing. Because there is no sequence
      constraint surrounding the site of 4-thioU substitution, this method should be
      applicable to many other RNAs.

PMID- 10208813
TI  - Site-specific derivatization of RNA with photocrosslinkable groups.
AB  - Derivatization of RNA with heterobifunctional photocrosslinking reagents becomes
      an increasingly popular method for the analysis of structural properties of
      ribonucleoprotein complexes. This article describes a simple chemical
      modification-derivatization strategy used to introduce selected chemical groups
      at specific internal positions within the RNA ribose backbone. The strategy is
      based on the coupling of a haloacetyl adduct to a thiol residue in the
      phosphodiester bond. The use of a number of RNA probes derivatized with several
      different photoreactive groups can provide invaluable information on the
      structural distribution of components in complex ribonucleoprotein assemblies.

PMID- 10208814
TI  - Bridging sulfur substitutions in the analysis of pre-mRNA splicing.
AB  - Accurate excision of intervening sequences (introns) from messenger RNA
      precursors is accomplished by a very large and complicated ribonucleoprotein
      complex called the spliceosome. Elucidating the mechanisms of the two
      phosphotransesterification reactions that result in intron removal is important
      for our understanding of the molecular evolution of early genetic systems, as
      well as our knowledge of contemporary eukaryotic gene expression. The functional
      consequences of systematic alterations in the reactive groups can be invaluable
      for understanding catalytic mechanisms, especially for enzymes, such as the
      spliceosome, whose size and complexity place them beyond the reach of
      crystallographic and spectroscopic analysis. One type of modification that can be
      incorporated into a scissile phosphate linkage is the phosphorothiolate, in which
      a bridging phosphate oxygen is substituted with sulfur. Phosphorothiolate
      substitutions can be used to detect metal ion-ligand interactions by a "metal
      specificity switch" strategy. I review recent advances in the synthesis,
      incorporation, and manipulation of nucleoside phosphorothiolates (with an
      emphasis on 3'-S-phosphorothiolates), and describe their utility in the study of
      pre-mRNA splicing.

PMID- 10208815
TI  - Nucleotide analog interference mapping.
AB  - Single-atom substitution experiments provide atomic resolution biochemical
      information concerning RNA structure and function. Traditionally, these
      experiments are performed using chimeric RNAs generated by reassembly of full
      length RNA from a synthetic substituted oligonucleotide and a truncated RNA
      transcript. Unfortunately, this technique is limited by the technical difficulty
      of assembling and measuring the effect of each singly substituted molecule in a
      given RNA. Here we review an alternate method for rapidly screening the effect of
      chemical group substitutions on RNA function. Nucleotide analog interference
      mapping is a chemogenetic approach that utilizes a series 5'-O-(1-thio)
      nucleoside analog triphosphates to simultaneously, yet individually, probe the
      contribution of a functional group at every nucleotide position in an RNA
      molecule. A population of randomly substituted RNAs is prepared by including
      phosphorothioate-tagged nucleotide analogs in an in vitro transcription reaction.
      The active molecules in the RNA population are selected by an activity assay, and
      the location of the analog substitution detrimental to activity is identified by
      cleavage at the phosphorothioate tag with iodine and resolution of the cleavage
      fragments by gel electrophoresis. This method, which is as easy as RNA
      sequencing, is applicable to any RNA that can be transcribed in vitro and has an
      assayable function. Here we describe protocols for the synthesis of
      phosphorothioate-tagged analogs and their incorporation into RNA transcripts. The
      incorporation properties and unique biochemical signatures of each individual
      analog are discussed.

PMID- 10208816
TI  - Use of circular permutation and end modification to position photoaffinity probes
      for analysis of RNA structure.
AB  - Photocrosslinking allows first-order structural analysis with relatively small
      amounts of biological material and can be applied in complex in vitro systems. In
      this article we describe methods for positioning both arylazide and
      thionucleotide photoagents within an RNA of interest by end modification of
      circularly permuted RNAs. Application of this technique provided a library of
      constraints that, together with biochemical and phylogenetic comparative data,
      were used to develop a structure model of the bacterial ribonuclease P ribozyme
      substrate complex. Circularly permuted genes for in vitro transcription are
      generated by PCR from tandem genes. Circularly permuted RNA transcripts can be
      modified with high efficiency at both the 5' and 3' termini with arylazide
      crosslinking reagents, or transcription can be primed with photoactive nucleotide
      analog monophosphates such as 6-thioguanosine. These crosslinking agents can be
      used over a wide range of experimental conditions but remain inert until they are
      activated by UV light. Crosslinked sites are subsequently mapped by reverse
      transcriptase primer extension of gel-purified crosslinked species. In addition
      to providing basic protocols for these methods, we discuss approaches for
      establishing the relevance of crosslinking data to native RNA structure.

PMID- 10208818
TI  - Thiol-containing RNA for the study of structure and function of ribozymes.
AB  - RNA performs multiple functions in cellular environments, such as transferring
      genetic information, catalyzing chemical reactions, and providing an integral
      component of ribonucleoprotein complexes involved in mRNA processing and
      translation. Many of these functions are poorly understood, mainly due to the
      lack of structural information. Because limited information has been obtained by
      physical and biophysical techniques, chemical and biochemical methods have been
      extensively used for studying RNA structure. This article outlines one such
      method which relies on site-specific incorporation of thiols into RNA. A brief
      overview of the methods for incorporation of thiols into RNA is followed by a
      detailed description of a procedure which utilizes postsynthetic modification of
      2'-amino-containing RNA for incorporation of thiols. The use of thiol-containing
      RNA to form disulfide cross-links for the study of the structure and dynamics of
      ribozymes is subsequently described.

PMID- 10208817
TI  - Site-specific labeling of RNA with fluorophores and other structural probes.
AB  - Site-specific probes provide a powerful tool for structure and function studies
      of nucleic acids, especially in elucidating tertiary structures of large
      ribozymes and other folded RNA molecules. Among many types of extrinsic labels,
      fluorophores are most attractive because they can provide structural information
      at millisecond time resolution, thus allowing real-time observation of structural
      transition during biological function. Methods for introducing fluorophores in
      RNA molecules are summarized here. These methods are robust and readily
      applicable to the labeling of other types of probes. However, as each case of RNA
      modification is unique, fine tuning of the general methodology is beneficial.

PMID- 10208821
TI  - Modulation of Sensory Nerve Function in the Airways.

PMID- 10208820
TI  - Preface.

PMID- 10208819
TI  - Directed cleavage of RNA with protein-tethered EDTA-Fe.
AB  - There are several methods for locating the RNA site where a protein binds. One of
      the less common methods is directed cleavage of the RNA by an EDTA-Fe reagent
      tethered to the protein. The reaction of the EDTA-Fe(III) with ascorbate or
      hydrogen peroxide produces reactive oxygen species, such as hydroxyl radicals,
      localized within a 10-A radius of the iron center. The reactive oxygen species
      will attack the ribose or deoxyribose of nucleic acids as well as proximal
      polypeptide backbones. One EDTA-Fe reagent, (EDTA-2-aminoethyl)-2-pyridyl
      disulfide complexed to iron (EPD-Fe), has been tethered to several proteins
      through a disulfide linkage to engineered cysteine thiols and used to cleave DNA,
      proteins, and RNA. A second tethered EDTA-Fe reagent, 1-(p-bromoacetamidobenzyl)
      EDTA-Fe, or BABE, has also been used to cleave RNA. Here we describe the issues
      involved in using these reagents with any RNA binding protein.

PMID- 10208823
TI  - Nitric Oxide and Airways.

PMID- 10208822
TI  - Tachykinins and Airway Function.

PMID- 10208824
TI  - Role of Epithelial Cells in Asthma.

PMID- 10208825
TI  - Airways Remodelling in Asthma.

PMID- 10208826
TI  - Cytokines and Airways: Recent Insights and Therapeutic Implications.

PMID- 10208827
TI  - Anticholinergic Agents.

PMID- 10208828
TI  - Leukotriene Antagonists.

PMID- 10208829
TI  - Open Questions on Guidelines for Treatment of Asthma and COPD.

PMID- 10208830
TI  - Cytoprotective effect of ulinastatin, a Kunitz-type protease inhibitor, on
      hypoxic injury in L2 cells treated with antimycin A via stabilization of
      lysosomal fragility.
AB  - The cytoprotective effect of ulinastatin, a Kunitz-type protease inhibitor, was
      studied in L2 cells treated with antimycin A, which induces depletion of cellular
      adenosine triphosphate (ATP), so-called <<chemical hypoxia>>. Antimycin A
      treatment with 2 microM significantly elevated the release of N-acetyl-beta-D
      glucosaminidase (NAG), a lysosomal enzyme, to 51.99+/-7.36%. In this condition,
      ulinastatin tended to inhibit the release of NAG at a concentration of 1000 U/ml
      (39.74+/-3.80%) and significantly ameliorated it at a concentration of 3000 U/ml
      (32.35+/-4.17%). Furthermore, ulinastatin at 10 U/ml showed a suppression on the
      fragility of lysosomal membrane isolated from L2 cells. These results indicate
      that ulinastatin has a prominent protective effect on hypoxic injury in L2 cells,
      and the lysosomal stabilizing effect is possibly involved as a mechanism of this
      action.

PMID- 10208831
TI  - Angiotensin II-mediated potentiation of endothelin-1-evoked bronchial
      contractions: a role for leukotrienes?
AB  - Angiotensin II potentiates the contractions evoked by endothelin-1. Previous
      studies have suggested that the mechanism underlying this effect may involve
      leukotrienes. The effects of the leukotriene synthesis inhibitor MK886 and of the
      leukotriene receptor antagonist ICI 198615 on angiotensin II-mediated
      potentiation of endothelin-1-induced contractions were examined. The ability of
      exogenously applied leukotriene D4 (3x10(-9)M) to potentiate the endothelin-1
      induced contractions was also investigated. The presence of angiotensin II (3x10(
      7)M) potentiated the constrictions evoked by endothelin-1 (e.g. 170% increase at
      3x10(-7)M endothelin-1). In the presence of MK886 (10(-7)-10(-5)M), however, this
      potentiation was abolished. The presence of ICI 198615 (10(-7)-10(-5)M), likewise
      abolished the angiotensin II effect. The presence of leukotriene D4(3x10(-9)M),
      mimicked angiotensin II in significantly potentiating the endothelin-1-evoked
      responses. These data confirm previous work using nordihydroguaiaretic acid and
      suggest that leukotrienes contribute to the angiotensin II-mediated potentiation
      of endothelin-1-evoked contractions.

PMID- 10208832
TI  - Effect of SB 217242 on hypoxia-induced cardiopulmonary changes in the high
      altitude-sensitive rat.
AB  - The effects of SB 217242, a non-peptide endothelin (ET) receptor antagonist, were
      investigated against hypoxia-induced cardiopulmonary changes in high altitude
      sensitive rats. In isolated pulmonary artery rings, SB 217242 (30 n m)
      antagonized ET-1-induced contractions with a p KB of 8.0. There was no difference
      in the sensitivity to ET-1 or the potency of SB 217242 in pulmonary artery from
      normoxic rats vs. rats exposed to hypoxia (9% O2) for 14 days. However, there was
      a marked reduction in the maximum response to ET-1, but not to KCl or
      phenylephrine, in pulmonary artery from hypoxic rats; this phenomenon was
      inhibited by treatment of animals with SB 217242 (10.8 mg/day, ip by osmotic
      pump) for the 14-day hypoxic period. Furthermore, there was a significant
      reduction in carbachol-induced, endothelium-dependent relaxation of precontracted
      pulmonary artery from hypoxic animals; SB 217242 treatment during the hypoxic
      period did not influence this difference. Vehicle-treated rats exposed to 14-day
      hypoxia had 173% higher pulmonary artery pressures and 75% higher
      right/left+septum ventricular mass ratios compared to normoxic animals. SB 217242
      (3.6 or 10.8 mg/day, ip) markedly reduced (80 and 95%, respectively) hypoxia
      induced increases in pulmonary artery pressure. Right ventricular hypertrophy was
      inhibited by 40% at the 10.8 mg/day dose. Marked medial thickening and luminal
      stenosis of small and medium-sized pulmonary arteries was observed in hypoxic
      rats. The SB 217242-treated, hypoxia-exposed rats had comparable small and medium
      sized arteries to normoxic rats. Rats treated with SB 217242 (10.8 mg/day) for
      the last 14 days of a 28-day hypoxic exposure had significantly lower pulmonary
      artery pressures than those of vehicle-treated rats. In addition, the effects of
      the selective ETA receptor antagonist, SB 247083, and the selective ETB receptor
      antagonist, A-192621 (3.6 or 10.8 mg/day, ip), were compared against hypoxia
      induced increases in pulmonary artery pressure and plasma ET concentrations. SB
      247083, but not A-192621, inhibited hypoxia-induced pulmonary hypertension,
      whereas A-192621, but not SB 247083, significantly exacerbated hypoxia-induced
      increases in ET concentrations, suggesting that hypoxia-induced pulmonary pressor
      responses are mediated via ETA receptor activation, while ETB receptor blockade
      may alter clearance of hypoxia-induced elevated plasma ET. The inhibitory effects
      of SB 217242 on the functional and remodeling changes induced by hypoxia provide
      further evidence that ET may play a central role in pulmonary hypertension and
      that ET receptor antagonists may have a utility in the treatment of this disease.

PMID- 10208833
TI  - The role of sensory nerves in propranolol-induced bronchial hyperresponsiveness
      in the guinea-pig.
AB  - The racemic mixture propranolol (RS-(+/-)-, and the S-(-)- and R-(+)-) isomers of
      propranolol have been shown to induce bronchial hyperresponsiveness in the guinea
      pig unrelated to beta-adrenoreceptor occupancy, that is attenuated by vagal
      section and mediated via the generation of 5-lipoxygenase metabolites of
      arachidonic acid. We have investigated the role of sensory nerves in propranolol
      induced bronchial hyperresponsiveness in guinea-pigs. Airways responsiveness to
      acetylcholine, bradykinin and bombesin was determined before and 10 min after
      intravenous infusion with RS-(+/-)-, S-(-)- and R-(+)-propranolol (1 mg/kg) in
      vehicle and capsaicin-treated guinea-pigs. Propranolol (1 mg/kg, iv)
      significantly augmented the bronchoconstrictor response to acetylcholine,
      bradykinin and bombesin (P<0.001), an effect that was observed for RS-(+/-)-, S-(
      )- and R-(+)-propranolol. In capsaicin-treated animals, the increased airways
      responsiveness to acetylcholine following intravenous infusion of S-(-)
      propranolol was significantly inhibited. Capsaicin treatment tended to reduce the
      increase in airways responsiveness to bradykinin following infusion with R-(+)
      propranolol, but was only significant for the highest dose used. Similarly,
      capsaicin treatment had no effect on the ability of RS-(+/-)-, S-(-)- and R-(+)
      propranolol to enhance the bronchoconstrictor response to bombesin. Our results
      suggest that propranolol-induced bronchial hyperresponsiveness to certain
      spasmogens is in part mediated by the action of capsaicin-sensitive nerves.

PMID- 10208834
TI  - Effects of dextran on tracheal mucociliary velocity in dogs in vivo.
AB  - We have previously shown that dextran (molecular weight 4kDa) is a potential
      mucolytic agent, reducing the viscoelasticity and spinnability of cystic fibrosis
      (CF) sputum and improving its mucociliary clearability during in vitro testing.
      We wished to see whether low molecular weight (LMW) dextran had similar effects
      on mucus rheology when administered by aerosol to living dogs, and whether the
      administration of dextran increased the rate of mucociliary clearance. Healthy
      mongrel dogs were anesthetized with pentobarbital and intubated. After a 30-min
      Ringer aerosol delivery during spontaneous breathing, tracheal mucociliary
      velocity (TMV by charcoal marker particle transport) was measured under
      bronchoscopic control, and mucus for viscoelasticity analysis (magnetic
      rheometer) was collected by the endotracheal tube method. Then LMW dextran in
      Ringer vehicle was delivered by aerosol via the endotracheal tube, followed by
      the same procedures. We performed eight experiments in eight dogs, involving 30
      min administrations of dextran aerosol; all dogs received inhalations of 20
      mg/ml, 65 mg/ml, and 200 mg/ml dextran. Compared with Ringer control, TMV
      increased to 145% of control (P=0.0417) at 65 mg/ml dextran. Mucus
      viscoelasticity (G*) significantly decreased to 19% of control (P=0.0426) at 65
      mg/ml. This in vivo study supports our previous in vitro testing, that LMW
      dextran decreases the mucus viscoelasticity and increases the rate of mucociliary
      clearance. We estimate the dosage received by aerosol at 65 mg/ml to be within
      the effective concentration range studied in vitro, i.e. 10-15 mg/ml final
      concentration. The results are consistent with the proposed mechanism that the
      saccharide moieties in LMW dextran compete for hydrogen bonding sites with other
      mucous glycoproteins. These new hydrogen bonds are structurally and rheologically
      ineffective, thus reducing the overall cross-link density, and making the mucus
      more easily cleared by ciliary and cough mechanisms.

PMID- 10208835
TI  - A new, simple method for measuring mucociliary clearance in guinea-pigs.
AB  - Airway mucociliary transport (MCT), which continuously removes inhaled particles
      and cellular debris from deep in the lung, is impaired in a number of diseases
      such as bronchitis and asthma. In order to determine the effects of candidate
      drugs on MCT function in the airway, a new in situ method to measure MCT function
      was established. MCT function is represented by the distance a gelatin solution
      containing Evans blue as a marker moves after injection into the trachea. The
      basal rate of dye transport in non-treated guinea-pigs was 4.4+/-0.2 mm/min. The
      beta2-adrenoceptor agonist salbutamol (2, 6, 10, 20 mg/kg, po), dose-dependently
      accelerated the basal MCT rate. However, its effect was completely inhibited by
      pretreatment with the non-selective beta -adrenoceptor antagonist, propranolol (1
      mg/kg, iv). MCT function in guinea-pigs was significantly attenuated to 2.6+/-0.3
      mm/min by SO2 gas exposure. Salbutamol failed to prevent MCT dysfunction in SO2
      exposed animals at doses previously shown to accelerate basal MCT rate. This
      simple method is useful for estimating MCT function in several airway disease
      models and for examining new drugs designed to improve MCT function in airway
      diseases.

PMID- 10208836
TI  - Enhancement by reproterol of the ability of disodium cromoglycate to stabilize
      rat mastocytes.
AB  - The beta2-adrenoceptor agonist reproterol and disodium cromoglycate (DSCG) are
      used in fixed combination for the treatment of asthma, because they act on
      bronchial smooth muscle and inflammatory cells, respectively. Here, we
      investigated if reproterol can also act in rat mast cells in vitro to facilitate
      the inhibitory action of disodium cromoglycate (DSCG) on histamine secretion
      induced by compound 48/80. Reproterol was as potent as DSCG to inhibit histamine
      release in rat mast cells (32.8+/-6.0 vs. 36.7+/-6.2% at 1 microM of each
      compound, n=10 and n=8 respectively). Mast cell stabilization by DSCG (1-100
      microM) was strongly and significantly enhanced in the presence of a fixed
      saturating concentration of reproterol (100 microM). Conversely, the combination
      of DSCG (1-100 microM) with the beta2-agonist used as reference compound,
      salbutamol (100 microM) did not inhibit histamine release more than DSCG alone.
      In combination with a saturating concentration of DSCG (100 microM), reproterol
      inhibited histamine release more than reproterol alone. The potent adenylate
      cyclase stimulator forskolin (50 microM) was able to inhibit histamine release to
      a similar extent as DSCG and significantly (P<0.05) enhanced the inhibition of
      histamine release by DSCG. Finally, the phosphodiesterase inhibitor theophylline
      (100 microM) was equipotent to reproterol and DSCG in stabilizing rat mast cells.
      In conclusion, reproterol enhances the ability of disodium cromoglycate to
      stabilize rat mast cells. This effect is not shared by salbutamol and can be, at
      least in part, independent of beta2-adrenoceptor stimulation.

PMID- 10208837
TI  - CTP:phosphocholine cytidylyltransferase: insights into regulatory mechanisms and
      novel functions.
AB  - A key regulatory enzyme in phosphatidylcholine biosynthesis, CTP:cholinephosphate
      cytidylyltransferase (CCT), catalyzes the formation of CDP-choline. This review
      discusses the essential features of CCT and addresses intriguing new insights
      into the catalytic and regulatory properties of this complex enzyme.
      Characterization of a lipid-binding segment in rat CCT is described and the role
      of lipids in CCT activation is discussed. An analysis of the phosphorylation
      domain is presented and possible physiological rationales for reversible
      phosphorylation of CCT are discussed. The nuclear localization of CCT is examined
      in the context of multiple CCT isoforms, as is recent evidence establishing a
      potential link between CCT activity and vesicular transport.

PMID- 10208838
TI  - Formation of phospholipid hydroperoxides and its inhibition by alpha-tocopherol
      in rat brain synaptosomes induced by peroxynitrite.
AB  - Peroxynitrite resulted from the reaction of nitric oxide and superoxide anion has
      been implicated in the genesis of neurotoxicity. In this study, the oxidation of
      phospholipids in rat brain synaptosomes induced by peroxynitrite generated from 3
      morpholinosydnonimine (SIN-1) was studied in vitro. The formation and
      accumulation of phospholipid hydroperoxides, including phosphatidylcholine
      hydroperoxide (PCOOH) and phosphatidyl-ethanolamine hydroperoxide (PEOOH) in rat
      brain synaptosomes induced by peroxynitrite, were observed. PEOOH and PCOOH were
      formed rapidly and SIN-1 concentration-dependently. The hydroperoxides formed in
      synaptosomes were unstable and it was suggested that phospholipase A2 played a
      role in degradation of the hydroperoxides. The endogenous alpha-tocopherol acted
      as a potent antioxidant. It was oxidized very rapidly and concentration
      dependently by SIN-1 to alpha-tocopheryl quinone. Furthermore, uric acid was
      found to be an effective antioxidant in inhibiting oxidative damage to
      synaptosomal lipids induced by SIN-1. The results provide direct evidence to show
      that peroxynitrite can not only deplete alpha-tocopherol, but also cause
      production of phospholipid hydroperoxides resulting in disrupted brain tissue.

PMID- 10208840
TI  - In vitro codon-reading specificities of unmodified tRNA molecules with different
      anticodons on the sequence background of Escherichia coli tRNASer.
AB  - The codon-reading properties of wobble-position variants of the unmodified form
      of Escherichia coli tRNASer1 (the UGA anticodon) were measured in a cell-free
      translation system. Two variants, with the AGA and CGA anticodons, each
      exclusively read a single codon, UCU and UCG, respectively. The only case of
      efficient wobbling occurred with the variant with the GGA anticodon, which reads
      the UCU codon in addition to the UCC codon. Surprisingly, this wobble reading is
      more efficient than the Watson-Crick reading by the variant with the AGA
      anticodon. Furthermore, we prepared tRNA variants with AA, UC, and CU, instead of
      GA, in the second and third positions and measured their relative efficiencies in
      the reading of codons starting with UU, GA, and AG, respectively. The specificity
      concerning the wobble position is essentially the same as that in the case of the
      codons starting with UC.

PMID- 10208839
TI  - S 17092-1, a highly potent, specific and cell permeant inhibitor of human proline
      endopeptidase.
AB  - Several lines of evidence indicate that proline endopeptidase (PE) could
      participate to the symptomatology and/or etiology of Alzheimer's disease. Thus,
      proline endopeptidase appears to contribute to the degradation of neuropeptides
      involved in learning and memory and could also control the production of the
      amyloidogenic peptide Abeta. Therefore the design of potent, selective and
      permeant inhibitors of human PE should lead to potential probes to assess the
      genuine contribution of this enzyme in Alzheimer's pathology. A novel
      perhydroindol carboxylic derivative, S17092-1 inhibits the hydrolysis of Z-Gly
      Pro-7AMC-hydrolysing activity present in human brain nuclei with a high affinity
      (Ki = 1 nM) and behaves as a highly potent (Ki = 1.5 nM) inhibitor of partially
      purified human PE. By contrast, S17092-1 is unable to affect a series of other
      peptidases including aminopeptidases B and M, dipeptidylaminopeptidase IV,
      endopeptidases 3.4.24.11, 3.4.24.15, 3.4.24.16, calpains and angiotensin
      converting enzyme. Furthermore, we show that the embryonic human kidney 293 cell
      line displays an intracellular PE-like activity that is blocked after
      preincubating cells with S17092-1, indicating that this inhibitor penetrates in
      HEK293 cells and could affect intracellular human PE. Altogether, we establish
      that S17092-1 behaves as a highly potent, specific and cell permeant inhibitor of
      human proline endopeptidase and can be seen as a probe to examine PE contribution
      in Alzheimer's disease.

PMID- 10208841
TI  - Phosphatidylinositol-3 kinase dependent MAP kinase activation via p21ras in
      endothelial cells exposed to cyclic strain.
AB  - Hemodynamic forces play a key role in the modulation of the morphology and
      function of the endothelium by activating several kinases. We have previously
      shown that cyclic strain, a repetitive mechanical stretch, induces activation of
      extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), members of the
      mitogen activated protein (MAP) kinase family. In order to investigate the
      upstream pathway of strain-induced ERK1/2 activation, we examined p21ras
      activation by cyclic strain and the effect of wortmannin and LY294002,
      phosphatidylinositol-3 kinase (PI 3-kinase) inhibitors on ERK1/2 phosphorylation.
      Cyclic strain induced a transient and rapid activation of p21ras at 1 min after
      strain. Wortmannin inhibited strain-induced ERK1/2 activation by 56.3 and 86.3 %,
      respectively. LY294002 inhibited ERK1 activation completely and ERK2 activation
      by 42.9%. These results suggest a possible involvement of p21ras and PI 3-kinase
      in the signal transduction pathway leading to the strain-induced ERK1/2
      activation.

PMID- 10208842
TI  - IRF-1 is an essential mediator in IFN-gamma-induced cell cycle arrest and
      apoptosis of primary cultured hepatocytes.
AB  - IFN-gamma induces cell cycle arrest and p53-independent apoptosis in primary
      cultured hepatocytes. However, it is not yet understood what molecules regulate
      the mechanism. We report here that interferon regulatory factor 1 (IRF-1) is an
      essential molecule in these phenomena. Hepatocytes from IRF-1-deficient mice were
      completely resistant to IFN-gamma in apoptosis indicated by three different
      hallmarks such as LDH release, DNA fragmentation and the activation of caspase-3
      family. Caspase-1 expression was little detected in hepatocytes, and constitutive
      and IFN-gamma-induced mRNA expression of Fas or caspase-3 did not change in
      between wild type and IRF-1-deficient hepatocytes. Expression of IFN-gamma
      inducible caspase, caspase-11, did not change either. Thus, it is unlikely that
      these molecules directly regulate the mechanisms. Interestingly, IRF-1-deficient
      hepatocytes were also resistant to IFN-gamma-induced cell cycle arrest despite
      IFN-gamma-induced cell cycle arrest and apoptosis are regulated by independent
      pathways. Results by Northern blot analysis showed that IFN-gamma-induced but not
      constitutive p53 mRNA expression was regulated by IRF-1. In fact, IFN-gamma did
      not induce cell cycle arrest in p53-deficient hepatocytes. Taken together, IRF-1
      mediates IFN-gamma signaling into primary hepatocytes for cell cycle arrest via
      p53 expression and for apoptosis.

PMID- 10208843
TI  - The development of extraocular muscle calcium homeostasis parallels visuomotor
      system maturation.
AB  - Extraocular muscle is modulated by unique genetic and epigenetic factors to
      produce an atypical phenotype. As a prelude to regulation studies, we
      characterized the development of cation homeostasis in the predominately fast
      twitch extraocular muscles. By atomic absorption spectroscopy, total muscle
      calcium content declined from birth to postnatal day 27 and, thereafter,
      stabilized at a low level in limb but increased dramatically in extraocular
      muscle (to 40x limb values). By ELISA, the slow isoform of sarcoplasmic reticulum
      Ca2+-ATPase predominated in neonatal eye muscle, but subsequently was largely
      replaced by the fast isoform. This replacement in eye muscle was completed later
      than in limb. Residual, slow Ca2+-ATPase likely resides in an unusual slow tonic
      fiber type characteristic of eye muscle. Maturation of the definitive extraocular
      muscle Ca2+-ATPase pattern paralleled myofiber Ca2+ and sarcoplasmic reticulum
      content. These data show that, like myosin heavy chain expression patterns, the
      development of cation homeostatic mechanisms in extraocular muscle parallels
      landmarks in the maturation of vision and eye movement control systems. Findings
      suggest that cation homeostasis in extraocular muscle may be susceptible to
      perturbations of the developing visual sensory system, as we have previously
      shown for myosin.

PMID- 10208844
TI  - Role of inducible nitric oxide synthase in leukocyte extravasation in vivo.
AB  - Several recent studies have suggested that nitric oxide (NO) derived from the
      inducible isoform of NO synthase (NOS) may act as an endogenous modulator of the
      inflammatory response by inhibiting adhesion of leukocytes to endothelial cells
      in vitro. Few studies have addressed specifically the role of iNOS in regulating
      leukocyte recruitment in vivo in a model of acute inflammation. Thus, the
      objective of this study was to assess the role of iNOS in modulating neutrophil
      (PMN) extravasation in an oyster glycogen-induced model of acute peritonitis in
      rats. Data obtained in the present study demonstrates that injection (IP) of
      oyster glycogen induces massive and selective PMN recruitment into the peritoneal
      cavity of rats at 6 hrs following OG administration. These extravasated cells
      were found to contain significant amounts of iNOS protein as assessed by Western
      blot analysis. Treatment of rats with the selective iNOS inhibitor L-iminoethyl
      lysine (L-NIL) dramatically reduced NO levels in lavage fluid as measured by
      decreases in nitrate and nitrite concentrations without significantly affecting
      iNOS protein levels. Although L-NIL inhibited NO production by >70%, it did not
      alter oyster glycogen-induced PMN recruitment when compared to vehicle-treated
      rats. We conclude that PMN-associated, iNOS-derived NO does not play an important
      role in modulating extravasation of these leukocytes in this model of acute
      inflammation.

PMID- 10208845
TI  - Cell reactions to dielectrophoretic manipulation.
AB  - The phenomenon of dielectrophoretic particle manipulation holds promise for many
      biotechnology applications, including cell sorting. In our system cell
      manipulation normally involves transient exposure (15 minutes) to radio-frequency
      AC electric fields generated using planar microelectrodes. The present study was
      designed to investigate the range of acute effects of dielectrophoretic
      manipulation on the normal physiology of isolated cells. Cells were suspended in
      isoosmotic Mannitol and exposed to a 5 MHz, 21 V (peak to peak) electric field
      with 100 micrometer gap electrodes. Cells were assigned to three experimental
      groups; non-exposed controls, exposed cells processed immediately after cessation
      of the field, and exposed cells processed after a time delay. SEM observations of
      spread cells cultured on the devices showed no apparent acute effects of field
      exposure on cell morphology. Cell-doubling rates in exposed cells subsequent to
      field-exposure or transient incubation in mannitol were no different from control
      cells. An MTT 'mitochondrial stress' assay indicated no alteration in the rate of
      oxidative respiration in exposed cells 0.5 hour after exposure to the field.
      Western blot analysis indicated upregulation of fos protein in cells 0.5 hour
      after field-exposure, which was confirmed using densitometry. Reverse
      transcription of cellular mRNA followed by PCR amplification, polyacrylamide gel
      electrophoresis and autoradiography of cDNA banding revealed differential gene
      expression between controls and exposed cells processed immediately after
      cessation of the field. Differential gene expression persisted in exposed cells
      at least 0.5 hours after removal from the field. Observations indicated that
      temperature fluctuation in the mannitol solution was minimal, suggesting that
      upregulated mRNA may not have been related to thermally-induced heat shock
      protein. The present study has indicated that exposure to AC fields during
      dielectrophoretic cell manipulation is associated with upregulation of the
      intermediate-early gene cfos and also transcription of other as yet unidentified
      genes. These transcriptional events were not manifest as gross changes in cell
      morphology or cell-cycle dynamics.

PMID- 10208846
TI  - The novel sarcomeric protein telethonin exhibits developmental and functional
      regulation.
AB  - We have isolated a cDNA clone from a mouse skeletal muscle library which is
      preferentially expressed in striated muscle and exhibits a high homology to human
      telethonin, a sarcomeric protein. The mouse telethonin transcript is
      developmentally regulated in both cardiac and skeletal muscle in vivo and is down
      regulated in response to denervation. In the C2C12 muscle cell-line the mouse
      telethonin transcript exhibited a pattern of accumulation similar to that
      observed for a contractile protein and suggests a role in myofibrillar assembly.

PMID- 10208847
TI  - Role of the His273 located in the sixth transmembrane domain of the angiotensin
      II receptor subtype AT2 in ligand-receptor interaction.
AB  - Angiotensin II receptor subtypes AT1 and AT2 are proteins with seven
      transmembrane domain (TMD) topology and share 34% homology. It was shown that
      His256, located in the sixth TMD of the AT1 receptor, is needed for the agonist
      activation by the Phe8 side chain of angiotensin II, although replacing this
      residue with arginine or glutamine did not significantly alter the affinity
      binding of the receptor. We hypothesized that the His273 located in the sixth
      transmembrane domain of the AT2 receptor may play a similar role in the functions
      of the AT2 receptor, although this residue was not identified as a conserved
      residue in the initial homology comparisions. Therefore, we replaced His273 of
      the AT2 receptor with arginine or glutamine and analyzed the ligand-binding
      properties of the mutant receptors using Xenopus oocytes as an expression system.
      Our results suggested that the AT2 receptor mutants His273Arg and His273 Glu have
      lost their affinity to [125I-Sar1-Ile8]Ang II, a peptidic ligand that binds both
      the AT1 and AT2 receptors and to 125I-CGP42112A, a peptidic ligand that binds
      specifically to the AT2 receptor. Thus, His273 located in the sixth TMD of the
      AT2 receptor seems to play an important role in determining the binding
      properties of this receptor. Moreover, these results along with our previous
      observation that the Lys215 located in the 5th TMD of the AT2 receptor is
      essential for its high affinity binding to [125I-Sar1-Ile8]Ang II indicate that
      key amino acids located in the 5th and 6th TMDs of the AT2 receptor are needed
      for high affinity binding of the AT2 to its ligands.

PMID- 10208848
TI  - Fabry disease: identification of novel alpha-galactosidase A mutations and
      molecular carrier detection by use of fluorescent chemical cleavage of
      mismatches.
AB  - Fabry disease (FD) (angiokeratoma corporis diffusum) is an X-linked inborn error
      of glycosphingolipid metabolism caused by defects in the lysosomal alpha
      galactosidase A gene (GLA). The enzymatic defect leads to the systemic
      accumulation of neutral glycosphingolipids with terminal alpha-galactosyl
      moieties. Clinically, affected hemizygous males have angiokeratoma, severe
      acroparesthesia, renal failure, and vasculopathy of the heart and brain. While
      demonstration of alpha-galactosidase deficiency in leukocytes is diagnostic in
      affected males, enzymatic detection of female carriers is often inconclusive, due
      to random X-chromosomal inactivation, underlining the need of molecular
      investigations for accurate genetic counseling. By use of chemical cleavage of
      mismatches adapted to fluorescence-based detection systems, we have characterized
      the mutations underlying alpha-Gal A deficiency in 16 individuals from six
      unrelated families with FD. The mutational spectrum included five missense
      mutations (C202W, C223G, N224D, R301Q, and Q327K) and one splice-site mutation
      [IVS3 G(-1) --> C]. Studies at the mRNA level showed that the latter led to
      altered pre-mRNA splicing with consequent alteration of the mRNA translational
      reading frame and generation of a premature termination codon of translation. By
      use of this strategy, carrier status was accurately assessed in all seven at-risk
      females tested, whereas enzymatic dosages failed to diagnose or exclude
      heterozygosity.

PMID- 10208849
TI  - Apolipoprotein(a), a link between atherosclerosis and tumor angiogenesis.
AB  - Lipoprotein (a) [Lp(a)] is a LDL-like particle with one apolipoprotein(a)
      [apo(a)] covalently bound to apolipoprotein B, the structural protein of Low
      Density Lipoprotein (LDL). Lewis Lung Carcinoma (LL/2) cells exhibited delayed
      growth and reduced angiogenesis in apo(a) transgenic mice, expressing a
      recombinant apo(a) [r-apo(a)] with 18 kringle 4 repeats. The mean microvessel
      density of subcutaneous LL/2 tumors from apo(a) transgenic mice was significantly
      lower than that of tumors from control wild type mice. CHO cells secreting a
      truncated apo(a) protein with only six kringle 4 repeats did not exhibit delayed
      tumor growth nor did it impair angiogenesis. These data point to an unappreciated
      role of human apo(a) in angiogenesis and cancer biology. As angiogenesis is
      necessary for reendothelialization following vascular injury, suppression of
      angiogenesis by apo(a) may also contribute to the atherogenicity of apo(a). The
      differences between the truncated apo(a) and r-apo(a) are consistent with the
      higher atherogenicity of higher molecular weight isoforms.

PMID- 10208851
TI  - Expression of extended polyglutamine sequentially activates initiator and
      effector caspases.
AB  - To date, eight neurodegenerative disorders, including Huntington's disease and
      dentatorubral-pallidoluysian atrophy, have been identified to be caused by
      expansion of a CAG repeat coding for a polyglutamine (polyQ) stretch. It is,
      however, unclear how polyQ expansion mediates neuronal cell death observed in
      these disorders. Here, we have established a tetracycline-regulated expression
      system producing 19 and 56 repeats of glutamine fused with green fluorescent
      protein. Induced expression of the 56 polyQ, but not of the 19 polyQ stretch
      caused marked nuclear aggregation and apoptotic morphological changes of the
      nucleus. In vitro enzyme assays and Western blotting showed that polyQ56
      expression sequentially activated initiator and effector caspases, such as
      caspase-8 or -9, and caspase-3, respectively. Furthermore, using cell-permeable
      fluorogenic substrate, the activation of caspase-3-like proteases was
      demonstrated in intact cells with aggregated polyQ. This is the first direct
      evidence that the expression of extended polyQ activates caspases and together
      with the previous findings that some of the products of genes responsible for CAG
      repeat diseases are substrates of caspase-3 indicates an important role of
      caspases in the pathogenesis of these diseases.

PMID- 10208850
TI  - Reciprocal gene expression of osteoclastogenesis inhibitory factor and osteoclast
      differentiation factor regulates osteoclast formation.
AB  - Osteoblasts/stromal cells support the formation of osteoclast-like cells (OCL)
      from osteoclast progenitor cells via expressing a membrane-associated protein,
      osteoclast differentiation factor (ODF), in the presence of osteotropic factors,
      whereas the cells secrete a substantial amount of osteoclastogenesis inhibitory
      factor (OCIF) in the unstimulated state. There are both OCL formation-supporting
      and the nonsupporting cell lines in osteoblasts/stromal cell lineages. The
      mechanism that divides osteoblasts/stromal cell lines into the two types is not
      known. The present study reports that OCL formation-supporting cell line ST2
      showed a greatly increased level of ODF mRNA, whereas their OCIF mRNA was
      drastically diminished in the presence of 1alpha, 25(OH)2-dihydroxyvitamin D3 or
      prostaglandin E2. In contrast, MC3T3-E1 cells lacking OCL formation-supporting
      ability did not show a decrease in OCIF mRNA in response to the factors, despite
      a similar increase in ODF mRNA as ST2 cells. However, inactivated MC3T3-E1 cells
      secreting nothing supported OCL formation in coculture with human promyelocytic
      cells, HL60. On the contrary, ST2 cells did not support OCL formation from HL60
      cells when cocultured in medium conditioned by 1alpha, 25(OH)2 vitamin D3-treated
      MC3T3-E1. These findings indicate that reciprocal gene expression of ODF and OCIF
      in osteoblasts/stromal cells is essential for supporting OCL formation.

PMID- 10208853
TI  - HOXC5 and HOXC8 expression are selectively turned on in human cervical cancer
      cells compared to normal keratinocytes.
AB  - A growing number of data have sustained the involvement of homeobox genes
      expression deregulation in cancer. In this study, we have performed an exhaustive
      survey of the expression of the 39 class I HOX genes expressed in normal and
      malignant human cervix keratinocytes. Using RT-PCR, we observed that the vast
      majority (34/39) of HOX genes are expressed in normal keratinocytes. Only HOXA2,
      HOXA7, HOXC5, HOXC8 and HOXD12 were found to be silent. Interestingly, this
      pattern is conserved in the transformed keratinocytes (SiHa cells) except for the
      appearance of HOXC5 and HOXC8 mRNA. The HOXC5 and HOXC8 expression was also
      observed in two other transformed keratinocytes cell lines of independent
      origins, Eil-8 and 18-11S3, and confirmed by in situ hybridization. Our data add
      weight to the body of evidence attributing to a specific adult tissue a
      particular combination of expressed HOX genes and suggest that HOXC5 and/or HOXC8
      could be involved in the process leading to the transformation of cervical
      keratinocytes.

PMID- 10208852
TI  - The 37-amino-acid interdomain of dengue virus NS5 protein contains a functional
      NLS and inhibitory CK2 site.
AB  - The dengue virus NS5 RNA-dependent RNA polymerase has been detected in the
      nucleus of virus-infected mammalian cells. We demonstrate here for the first time
      using in vitro and in vivo assay systems that the 37-amino-acid linker
      interdomain of NS5 (residues 369 to 405) contains a nuclear localization sequence
      (NLS) which is capable of targeting b-galactosidase to the nucleus. Further, we
      show that the linker is recognized by subunits of the NLS-binding importin
      complex with an affinity similar to that of the bipartite NLS of the
      retinoblastoma protein and, in analogous fashion to proteins such as the SV40
      large tumor antigen, contains a functional protein kinase CK2 phosphorylation
      site (threonine 395). Interestingly, this site appears to inhibit NS5 nuclear
      targeting, probably through a cytoplasmic retention mechanism. The linker may
      have an important role in targeting NS5 to the nucleus in a regulated manner
      during the dengue virus infectious cycle.

PMID- 10208854
TI  - Molecular mechanisms for the hepatic uptake of magnetic resonance imaging
      contrast agents.
AB  - The mechanisms were investigated for the hepatic transport of 4 different
      gadolinium complexes used as contrast agents for magnetic resonance imaging
      (MRI). In basolateral rat hepatocyte plasma membrane vesicles, Gd-DTPA uptake was
      indistinguishable from non-specific binding to vesicles; Gd-BOPTA and Gd-EOB-DTPA
      entered plasma membrane vesicles following a linear, concentration-dependent
      mechanism up to 1.5 mM of substrate. By contrast, Gd-B 20790 uptake followed a
      saturative kinetic with an apparent Km of 92 +/- 15 microM and a Vmax of 143 +/-
      42 pmol/mg prot/15 sec, and it occurred into an osmotic-sensitive space.
      Sulfobromophthalein ant taurocholate, but not unconjugated bilirubin inhibited
      the uptake rate of Gd-B 20790 but not that of the other three compounds.
      Injection into Xenopus laevis oocytes of 5 ng of human OATP cRNA resulted, after
      3 days, in a >/=2-fold stimulation (p < 0.001) of transport of Gd-B 20790 but not
      of Gd-BOPTA or Gd-EOB-DTPA. Collectively, these data indicate that the hepatic
      uptake of the MRI contrast agent Gd-B 20790 is a carrier-mediated mechanism
      operated by OATP while MRI compounds with other chemical structures enter the
      hepatocyte by other mechanisms.

PMID- 10208855
TI  - Role of ground and excited singlet state oxygen in the red light-induced
      stimulation of Escherichia coli cell growth.
AB  - Irradiation of selected Escherichia coli defective strains with red-light induces
      a stimulation of the cell growth rate. Such effect is wavelength-dependent and is
      accompanied by a transient increase of the cell volume and some enzymic
      activities. The presence of oxygen appears to be essential for the occurrence of
      a significant photostimulatory effect. The results obtained upon irradiation in
      the presence of quenchers (tryptophan, histidine, azide) or enhancers (deuterium
      oxide) of singlet oxygen (1O2) strongly suggest that this activated oxygen
      derivative is generated by excitation of endocellular chromophores (possibly
      cytochromes). The reaction of 1O2 with nearby cellular targets could induce a
      sublethal cell damage which in turn promotes an accelerated cell metabolism.

PMID- 10208856
TI  - Repression of hepatitis B virus X gene expression by hammerhead ribozymes.
AB  - The X protein (HBx) of human hepatitis B virus (HBV) is a transcriptional
      activator protein. The HBx protein plays an important role in viral replication
      in HBV infected cells and the liver diseases including hepatitis, cirrhosis, and
      hepatocellular carcinoma (HCC). Therefore, the repression of HBx gene expression
      by hammerhead ribozymes may be a good way to inhibit HBV replication and cure HBV
      related liver diseases. We designed two hammerhead ribozymes, RzA and RzB, to
      cleave target sites at nucleotides 114 and 309 in the HBx open reading frame
      (ORF), respectively. In vitro, RzA and RzB cleaved HBx RNAs at their target sites
      up to 52 and 75%, respectively; however, the disabled ribozymes (dRzs) which have
      mutations in the catalytic site did not cleave the target RNAs at all. When each
      of the ribozymes were cotransfected into HepG2 cells with HBx expression plasmid,
      RzA and RzB reduced the level of HBx mRNA to 40 and 57%, respectively. The
      transactivation activity of HBx protein was also reduced dramatically by the
      ribozymes. These results suggest that the hammerhead ribozymes, RzA and RzB, can
      be used for the gene therapy of liver diseases caused by HBV.

PMID- 10208857
TI  - Characterization of low-affinity binding sites for glibenclamide on the Kir6.2
      subunit of the beta-cell KATP channel.
AB  - The ATP-sensitive K+ channel, an octameric complex of two structurally unrelated
      types of subunits, SUR1 and Kir6.2, plays a central role in the physiological
      regulation of insulin secretion. The sulfonylurea glibenclamide, which trigger
      insulin secretion by blocking the ATP-sensitive K+ channel, interacts with both
      high and low affinity binding sites present on beta-cells. The high affinity
      binding site has been localized on SUR1 but the molecular nature of the low
      affinity site is still uncertain. In this study, we analyzed the pharmacology of
      glibenclamide in a transformed COS-7 cell line expressing the rat Kir6.2 cDNA and
      compared with that of the MIN6 beta cell line expressing natively both the Kir6.2
      and the SUR1 subunits. Binding studies and Scatchard analysis revealed the
      presence of a single class of low affinity binding sites for glibenclamide on the
      COS/Kir6.2 cells with characteristics similar to that observed for the low
      affinity site of the MIN6 beta cells.

PMID- 10208858
TI  - Induction of apoptosis in cultured colon cancer cells by transfection with human
      interferon beta gene.
AB  - The growth of SW480 colon cancer cells following the transfection with the human
      interferon beta (hIFNbeta) gene entrapped in cationic multilamellar liposomes was
      effectively inhibited, but not that of the cells transfected with the gene from
      which the secretion signal sequence of hIFNbeta had been deleted. The amount of
      hIFNbeta secreted in the medium from SW480 cells transfected with hIFNbeta
      gradually increased and became maximum 3 days after the transfection, but no
      hIFNbeta was detected in the medium of the cells transfected with the secretion
      signal-deleted hIFNbeta. These findings indicate that the growth inhibition of
      SW480 cells after the transfection with hIFNbeta was caused by hIFNbeta secreted
      from the transfected cells. At that time, SW480 cells were induced to undergo
      apoptosis, which was identified by morphological aspects, viz., chromatin
      condensation, nuclear segmentation, and nucleosomal DNA fragmentation. The
      hIFNbeta-induced apoptosis was found to be linked to the activation of caspases 3
      and 8 as evidenced by immunoblot, enzymological, and cell death inhibition
      analyses.

PMID- 10208859
TI  - Hepatitis C virus NS5A protein is phosphorylated by casein kinase II.
AB  - Hepatitis C virus (HCV) has a positive-strand RNA genome that encodes a
      polyprotein, which is post-translationally processed by cellular and viral
      proteinases into three structural and six non-structural (NS) proteins. The NS5A
      protein, expressed in mammalian cells, exists as two phosphorylated forms of 56
      kDa and 58 kDa. In this study, we provide evidence for a stable association
      between NS5A and a protein kinase from rat-1 cells by affinity to immobilized
      glutathione-S-transferase (GST)-NS5A fusion protein. This protein kinase was
      associated through the N-terminus of NS5A and was not regulated by cell cycle.
      The GST-NS5A was also phosphorylated in vitro by the purified casein kinase II
      (CKII), a member of the CMCG kinase family. Since CKII and the NS5A-associated
      protein kinase have the same molecular size and property by In-gel kinase assay
      and an inhibitor treatment test, we conclude that HCV NS5A protein is
      phosphorylated by CKII.

PMID- 10208860
TI  - Heat stability of the potato tuber ADP-glucose pyrophosphorylase: role of Cys
      residue 12 in the small subunit.
AB  - Most of the ADP-glucose pyrophosphorylases from different sources are stable to a
      heat treatment. We found that in the potato (Solanum tuberosum L.) tuber enzyme,
      the intermolecular disulfide bridge located between Cys12 of the small subunits
      is responsible for the stability at 60 degrees C. When this unique disulfide bond
      is cleaved the enzyme is stable up to 40 degrees C. Mutation of Cys12 in the
      small subunit into either Ala or Ser yielded enzymes with stability similar to
      the reduced form of the wild type. Concurrently, the enzyme with a truncated
      small subunit on the N-terminal was stable only up to 40 degrees C. Thus, the N
      terminal is important for the stability of the enzyme because of the presence of
      a disulfide bond.

PMID- 10208861
TI  - High levels of circulating Abeta42 are sequestered by plasma proteins in
      Alzheimer's disease.
AB  - A previously unrecognized large pool of Abeta was discovered in freshly drawn
      plasma of patients diagnosed with Alzheimer's disease (AD) and non-demented
      control subjects. This Abeta pool was revealed after acid denaturation and
      chromatographic separation of plasma proteins followed by Abeta quantitation in
      the 4.5 kDa fractions by europium immunoassay. The mean values of Abeta42 in the
      AD and control individuals amounted to 236 ng/ml and 38 ng/ml, respectively.
      These Abeta values are on the average far higher than previously measured.
      Surprisingly, the circulating Abeta42 is about 16 times more abundant than
      Abeta40 in the AD population. Addition of Abeta to freshly drawn plasma
      demonstrated the rapid disappearance of Abeta epitopes, as detected by
      immunochemical techniques, suggesting either proteolytic degradation or Abeta
      sequestration. Incubation of Abeta with purified plasma proteins and lipoproteins
      rapidly decreases detectable levels of free Abeta suggesting epitope masking as
      the likely mechanism. The free and protein-bound Abetab in the circulation may
      represent a potential source for deposition in the cerebrovasculature and brain
      parenchyma of AD.

PMID- 10208862
TI  - High efficient expression of the functional ligand binding site of the inositol
      1,4,5-triphosphate receptor in Escherichia coli.
AB  - Type 1 inositol 1,4,5-trisphosphate receptor (IP3R1), an inositol 1, 4,5
      trisphosphate (IP3)-gated Ca2+ release channel, binds IP3 within the N-terminal
      ligand-binding region. Here we report an improved Escherichia coli expression
      system in which large amounts of the IP3 binding sites could be efficiently
      produced as soluble active proteins. We have found that the structures of IP3
      binding constructs expressed in E. coli significantly affect their production as
      soluble protein. Residues 1-604 (T604), which contain the putative protein
      folding units, yielded about 4.6% of the total soluble fraction. As a result,
      soluble active T604 would be 19 mg per liter of culture. The affinity for IP3 of
      T604 (Kd = 45 nM) is comparable to that of the native IP3R1, whereas that of an
      R441Q mutant is much higher (8.1 nM). This system should provide an invaluable
      and powerful means to unveil the molecular recognition of IP3R1 for IP3.

PMID- 10208863
TI  - Differential serine phosphorylation regulates IkappaB-alpha inactivation.
AB  - NF-kappaB is a ubiquitous transcription factor involved in the signal
      transduction mechanisms of the immune response, acute phase reactions, and viral
      infections. NF-kappaB proteins are retained in the cytoplasm by association with
      an inhibitor, termed IkappaB. Studies on the regulation of mammalian IkappaB
      alpha have revealed that two amino-terminal conserved phosphoserines are the
      target sites of incoming signals. We report that the corresponding amino-terminal
      phosphoserines of avian IkappaB-alpha are phosphorylation targets leading to
      inactivation of IkappaB-alpha upon stimulation. In addition, we show differential
      roles for these two serines. Mutation of serine 40 to alanine blocks all stimuli
      tested (TNF-alpha, phorbol ester, and anti-CD3 and anti-CD28), leading to NF
      kappaB activation, while mutation of serine 36 to alanine attenuates only certain
      transduced signals (PMA, TNF-alpha). These novel findings support the hypothesis
      that the amino-terminal phosphoserine residues of avian IkappaB-alpha
      differentially mediate NF-kappaB signal transduction pathways and activation by
      distinct signals, thereby resulting in the activation NF-kappaB.

PMID- 10208864
TI  - Genetic and biochemical evidence for a critical role of Janus kinase (JAK)-3 in
      mast cell-mediated type I hypersensitivity reactions.
AB  - We investigated the role of JAK3 in IgE receptor/FcepsilonRI-mediated mast cell
      responses. IgE/antigen induced degranulation and mediator release were
      substantially reduced with Jak3-/- mast cells from JAK3-null mice that were
      generated by targeted disruption of Jak3 gene in embryonic stem cells. Further,
      treatment of mast cells with 3'bromo-4'-hydroxylphenyl)-amino-6,7
      dimethoxyquinazoline (WHI-P154), a potent inhibitor of JAK3, inhibited
      degranulation and proinflammatory mediator release after IgE receptor/
      FcepsilonRI crosslinking. Thus, JAK3 plays a pivotal role in IgE receptor/
      FcepsilonRI-mediated mast cell responses and targeting JAK3 may provide the basis
      for new and effective treatment as well as prevention programs for mast cell
      mediated allergic reactions.

PMID- 10208865
TI  - Indian hedgehog in the late-phase differentiation in mouse chondrogenic EC cells,
      ATDC5: upregulation of type X collagen and osteoprotegerin ligand mRNAs.
AB  - Endochondral bone formation includes a cascade of cellular events such as
      proliferation, maturation, hypertrophic conversion and calcification of
      chondrocytes and the cartilage replacement by bone. During these processes,
      hypertrophic conversion and calcification of chondrocytes (the late-phase
      differentiation) is a crucial process of chondrogenic differentiation. Indian
      hedgehog (Ihh), a secreted protein expressed in early hypertrophic chondrocytes,
      is thought to be involved in regulation of hypertrophic conversion via a feedback
      loop through the perichondrium. In the present study, we showed by Northern
      analysis and in situ hybridization that Smoothened (Smo), a key component in
      hedgehog signal transduction, was expressed in chondrocytes in both adult mice
      and mouse embryos at 16 days post-coitum in vivo, suggesting that Ihh directly
      acts on chondrocytes. We previously reported that Ihh, Patched and Smo were all
      expressed in differentiated ATDC5 cells. Exogenously administered mouse
      recombinant N-terminal protein of Ihh (mrIhh-N) upregulated the gene expression
      of type X collagen, a phenotypic marker of hypertrophic chondrocytes, as well as
      osteoprotegerin ligand (OPGL), a potent stimulator of osteoclastogenesis and
      osteoclast activity, while it did not modulate the expression of Ihh itself, bone
      morphogenetic protein (BMP)-4, BMP-6, transforming growth factor (TGF)-beta1 and
      TGF-beta2 in differentiated ATDC5 cells. Moreover, when added to the osteoclast
      cultures, mrIhh-N markedly stimulated the formation of resorption pits on dentine
      slices. Our data support the hypothesis that Ihh stimulated the late-phase
      chondrogenic differentiation in differentiated ATDC5 cells and upregulated the
      gene expression of OPGL in these cells.

PMID- 10208866
TI  - Autoimmune regulator is expressed in the cells regulating immune tolerance in
      thymus medulla.
AB  - The AIRE gene (autoimmune regulator), coding for a putative transcriptional
      regulatory factor, is mutated in autoimmune-polyendocrinopathy-candidiasis
      ectodermal dystrophy (APECED). We have investigated the expression of the AIRE
      gene by mRNA in situ hybridization and immunohistochemistry in various human
      tissues. Here we show that AIRE is expressed in distinct cells in thymus medulla,
      and also in rare cells in lymph node paracortex and medulla, and in spleen and
      fetal liver, but not in the target organs of autoimmune destruction. Double
      immunofluorescence studies revealed that in thymus medulla both epithelial
      (cytokeratin positive) and non-epithelial cells expressed AIRE. Subcellularly,
      AIRE was localised in nuclear dots in thymus and lymph node and also in
      transfected cells. The cellular localisation of AIRE and its nuclear
      localisation, compatible with its predicted protein domains, suggest that AIRE
      may regulate the mechanisms involved in the induction and maintenance of immune
      tolerance.

PMID- 10208867
TI  - Angiotensin II activates the proinflammatory transcription factor nuclear factor
      kappaB in human monocytes.
AB  - The renin-angiotensin system may contribute to the pathogenesis of
      atherosclerosis. A common feature of all stages of atherosclerosis is
      inflammation of the vessel wall. The transcription factor nuclear factor-kappaB
      (NF-kappaB) participates in most signaling pathways involved in inflammation.
      This study therefore examined the effect of angiotensin (ANG) II on NF-kappaB
      activation in monocytic cells, a major cellular component of human atheroma, by
      electrophoretic mobility shift assay. ANG II, like TNFalpha, caused rapid
      activation of NF-kappaB in human mononuclear cells isolated from peripheral blood
      by Ficoll density gradient. This ANG II effect was blocked by the angiotensin AT1
      receptor antagonist losartan. Specificity of ANG II-induced NF-kappaB activation
      was ascertained by supershift and competition experiments. Moreover, ANG II
      stimulated NF-kappaB activation in human monocytes, but not in lymphocytes from
      the same preparation. Together, the data demonstrate the ability of the
      vasoactive peptide ANG II to activate inflammatory pathways in human monocytes.

PMID- 10208869
TI  - Involvement of Spt7p in vacuolar polyphosphate level of Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae became less sensitive to nickel by a defect of the SPT7
      gene encoding a transcription factor. Initial rate of nickel uptake by whole
      cells of a SPT7-negative mutant FY963 was nearly equal to that of the parent
      strain FY61, and FY963 accumulated nickel about 1.7-fold of the value of FY61
      when cultured in medium containing 0.1 mM NiCl2; most of which was sequestered
      into vacuoles. The pH gradient-driven nickel uptake by vacuolar membrane vesicles
      was not altered in FY963, but the amount of polyphosphate in vacuoles was highly
      elevated. Involvement of Spt7p in nickel detoxification through regulation of
      vacuolar polyphosphate level in S. cerevisiae was discussed.

PMID- 10208868
TI  - Transcription of the human thyrotropin-releasing hormone receptor gene-analysis
      of basal promoter elements and glucocorticoid response elements.
AB  - The gene for the human thyrotropin-releasing hormone receptor (TRHR) spans 35 kb
      and contains three exons and two introns (Matre et al. (1999) J. Neurochem. 72, 1
      11). Despite a reported transcription start site (TSS) mapped to position -885
      upstream of the translation initiation codon (Iwasaki et al. (1996) J. Biol.
      Chem. 271, 22183-8), we found cell type specific promoter activity directed by a
      fragment downstream of this site (-770 to +1). To elucidate the basis for this
      unexpected activity, we analyzed basal promoter elements in this region of the
      gene. One divergent TATA box, TTTAAA in position -759, was found by mutational
      analysis to be critical for promoter activity, providing a likely explanation for
      the basal activity observed. This proximal region apparently contains several
      promoter elements, including Pit-1 binding sequences within the first intron of
      the TRHR gene as previously reported. Here we describe the analysis of two
      putative glucocorticoid response elements (GREs) that we identified in this
      region, one (distal) half site overlapping the proposed TSS at -885 and one
      (proximal) full site within the first intron at position -624. Accordingly,
      stimulation of rat pituitary GH3 and GH4C1 cells with dexamethasone strongly
      enhanced transcription activity of a reporter construct containing the distal GRE
      half site and the proximal GRE site. Both sites bound the glucocorticoid receptor
      (GR) in a specific manner. Deletion of the distal GRE half site abolished the
      dexamethasone induction of CAT transcription, as did mutations in the proximal
      site. We therefore conclude that both sites are necessary for regulation of the
      TRHR gene transcription by glucocorticoids.

PMID- 10208870
TI  - Heparan sulfate composition of alternatively spliced CD44 fusion proteins.
AB  - Prior analyses of recombinant CD44 fusion proteins have indicated that
      combinatorial splicing of variant exons exerts distal effects on chondroitin
      sulfate content and structure, which may regulate the biological properties of
      the respective CD44 isoforms. The consequences of splicing of variant exons V4-7
      on the heparan sulfate moieties were therefore examined, utilizing recombinant
      chimeras containing exons V3 and V8-10, engineered with or without exons V4-7 and
      expressed as Ig fusion proteins in COS cells. Splicing of exons V4-7, though they
      contain no consensus motifs for glycosaminoglycan assembly, resulted in markedly
      increased polymer sulfation levels of the heparan sulfates. The sulfate groups of
      both the CD44 V3-10 and V3,8-10 isoforms occurred as di- and tri-sulfated
      dissacharide units and were restricted to one N-sulfated block domain within the
      polymers. Compared to native human keratinocyte CD44, the recombinant heparan
      sulfates were relatively low in sulfate content. Our data indicate that variant
      exon V4-7 splicing exerts distal effects on the composition of this
      glycosaminoglycan. These effects may regulate those functions that are mediated
      through the heparan sulfate moieties, such as the binding of growth factors.

PMID- 10208871
TI  - Species-specific alternative splicing of transgenic RNA in the mammary glands of
      pigs, rabbits, and mice.
AB  - Gene-farming techniques provide an effective tool for the production of
      recombinant proteins in livestock. Transgenes consisting of genomic DNA sequences
      are as a rule more efficiently expressed than those in which the product of
      interest is encoded by a cDNA. However, the processing of pre-mRNA from genomic
      constructs may yield unexpected messenger RNAs and subsequently protein variants.
      We describe the appearance of different alternative mRNA splice patterns of a
      gene construct in which a mutant human growth hormone (hGH-N) gene is
      transcriptionally controlled by 2.5 kb of mouse whey acidic protein (WAP2)
      regulatory sequences in the mammary gland of different livestock species.
      Compared to the transcription products in transgenic mice harboring the same gene
      construct and to cell transfection experiments, expression analysis in transgenic
      pigs and rabbits revealed different mRNA splice patterns with regard to the
      proportion of the processed transcripts. Apart from already-known physiological
      mRNA splice products, previously undescribed processed hGH transcripts were
      observed in these species. Sequence analysis of the transgenes suggests that the
      species-specific hGH mRNA patterns may be caused by species- and tissue-specific
      differences in trans-acting splice factors.

PMID- 10208872
TI  - The cysteine residues of recombinant human gastric lipase.
AB  - Recombinant human gastric lipase (rHGL) and three of its cysteine mutants
      (cysteine 227, 236, and 244 substitued for threonine or serine) were expressed in
      the baculovirus/insect cell system and purified to homogeneity by performing a
      two-step procedure. Substituting Ser for Cys 227 and Cys 236 resulted in mutant
      lipases with a significantly lower level of activity (30% and 22%, respectively)
      on a short chain triglyceride (tribuyrin) substrate, while the mutation at
      position 244 only slightly reduced the activity. Using 4, 4'-dithiopyridine (4
      PDS) as a sulfhydryl reagent on the above mutants, it was possible to clearly
      identify the single sulfhydryl residue at position 244 and consequently, the
      disulfide bridge at position 227-236. No potential disulfide bridges were formed
      during the protein folding between cysteines 227-244 or between cysteines 236
      244, as thought to occur in the case of rabbit gastric lipase (RGL). The present
      results are consistent with the recently determined 3D-structure of rHGL.

PMID- 10208873
TI  - Identification of receptor genes in renal cell carcinoma associated with
      angiogenesis by differential hybridization technique.
AB  - To screen the receptor genes in renal cell carcinoma (RCC) associated with
      angiogenesis, we performed differential hybridization of the cDNA library of
      membrane-type protein tyrosine kinases (mPTKs). Three thousand plaques of a mPTKs
      enriched cDNA library were screened with mPTKs mixture probes produced from
      hypervascular RCC tissues and RCC cell lines. Six different cDNA fragments of the
      PTK genes were isolated, and the sequence analysis showed that these represented
      cDNAs for TIE1, KDR, FMS, FGFR-4, JAK1 and HCK. Of these genes, the expression of
      TIE1, KDR, and FGFR-4 was studied in RCC tissue and cell lines by Northern blot
      analysis. We also investigated the expression of vascular endothelial growth
      factor (VEGF), placenta growth factor (PlGF) and their receptor FLT-1. In all the
      hypervascular RCC tissues, the amounts of mRNAs for KDR and FLT-1 were increased
      compared to adjacent normal tissues. The TIE1 and FGFR-4 genes were also
      overexpressed in most of the hypervascular RCC tissues, while no mRNA of KDR, FLT
      1, or TIE1 could be detected in any of the four human RCC cell lines. The amounts
      of the VEGF and PlGF mRNAs were increased in hypervascular RCC tissues, while
      VEGF mRNA was detected in the four cell lines but PlGF mRNA was not. FGFR-4 mRNA
      was expressed in three of the four cell lines. These results suggest that KDR,
      FLT-1, PlGF and TIE1 mRNAs are present in the mesenchymal cells of RCC, while
      VEGF and FGFR-4 genes are expressed in RCC cells themselves in vivo.

PMID- 10208874
TI  - The melanocortin 4 receptor mediates leptin stimulation of luteinizing hormone
      and prolactin surges in steroid-primed ovariectomized rats.
AB  - We have previously reported that leptin, the product of the obese (ob) gene, may
      play a physiologically relevant role in the generation of estradiol/progesterone
      induced luteinizing hormone (LH) and prolactin (PRL) surges in female rats. In
      the present study, we examined whether the stimulatory effect of leptin on the
      hormonal surges is mediated through the melanocortin (MC) 4 receptor in the
      brain, as is leptin's effect on feeding behavior. We also explored whether the
      MC4 receptor participates in tonic stimulation of steroid-induced LH and PRL
      surges. Experiments were performed on both normally fed and 3-day starved rats,
      which were ovariectomized and primed with estradiol and progesterone. At 11:00 h
      on the day of the experiments, the normally fed rats received an
      intracerebroventricular administration of artificial cerebrospinal fluid
      (vehicle), SHU 9119 (a nonselective MC3/MC4 receptor antagonist, 1.0 nmol), or
      HS014 (a selective MC4 receptor antagonist, 1.0 nmol). The 3-day starved rats
      were given vehicle, recombinant mouse leptin (0.3 nmol), leptin (0.3 nmol) +
      SHU9119 (1.0 nmol), or leptin (0.3 nmol) + HS014 (1.0 nmol). From 11:00 to 18:00
      h, blood was collected every 30 min to measure LH and PRL. The 3-day starvation
      completely abolished both LH and PRL surges, but leptin significantly reinstated
      these hormonal surges. Both SHU9119 and HS014 significantly decreased the
      magnitude of LH and PRL surges in normally fed rats and also significantly
      blocked the leptin stimulation of the hormonal surges in starved rats. These
      results suggest that the MC4 receptor may be the pivotal subtype of MC receptors
      mediating the leptin stimulation of LH and PRL surges. The data also suggest that
      endogenous MC(s) may tonically stimulate the hormonal surges in normally fed rats
      via the MC4 receptor. This is the first report describing a physiological role of
      a specific MC receptor in regulating the reproductive axis.

PMID- 10208875
TI  - Down-regulation of nucleophosmin/B23 mRNA delays the entry of cells into mitosis.
AB  - In investigating the regulation of nucleophosmin/B23 mRNA expression at the entry
      of mitosis, the results of Northern gel blot analysis showed that the
      nucleophosmin/B23 mRNA levels significantly increased in prometaphase (nocodazole
      arrested) or metaphase (colchicine-arrested) cells collected by mitotic shake
      off. A higher level of nucleophosmin/B23 mRNA was detected in all the collected
      mitotic cells arrested by treatment with nocodazole for 10-18h as compared to
      that in G2 cells. An attempt was then made to determine whether the regulation of
      nucleophosmin/B23 mRNA plays a role in the control of entry into mitosis. Down
      regulation of nucleophosmin/B23 mRNA by transfection of its antisense construct
      resulted in the delay of cells entering mitosis. The demonstration of the
      characteristic changes in the mRNA level of nucleophosmin/B23 during the entry of
      cells into mitosis implicates the importance of nucleophosmin/B23 in the control
      of the mitotic fate of nucleoli and cell growth.

PMID- 10208876
TI  - Yeast one-hybrid assay identifies YY1 as a binding factor for a proacrosin
      promoter element.
AB  - The proacrosin gene is specifically expressed in the testis and encodes an
      acrosomal enzyme. Previously, footprint analyses have shown binding of nuclear
      extracts from testis and brain to a highly conserved 17 bp motif (F1 element: 5'
      AACTTCAAAATGGCTCC/T-3') located in the proacrosin promoter. By using this DNA
      element as a target in a yeast one-hybrid assay, a cDNA fragment coding for the C
      terminal part of the transcription factor YY1 was isolated. The binding of YY1 to
      this F1 element was confirmed by immunocompetition in EMSA. Because putative YY1
      binding sites were also found in the promoters of other testis-specific genes,
      the YY1 transcription factor could play an important role in testicular gene
      expression.

PMID- 10208877
TI  - Rapid selection of tetracycline-controlled inducible cell lines using a green
      fluorescent-transactivator fusion protein.
AB  - We describe a modification of the tetracycline-controlled expression system that
      facilitates the rapid identification of tetracycline-sensitive clones. The
      TetR/VP16 transactivator protein was tagged with the green fluorescent protein
      (GFP) at its N-terminus. This results in a functional transactivator which allows
      cells expressing high levels of the modified transactivator to be selected by
      fluorescent-activated cell sorting. After expansion, single cell clones that
      maintain a high level of GFP fluorescence can be tested for their ability to
      transactivate a luciferase gene under control of the Tet operator, leading to the
      rapid identification of clones with strong inducibility.

PMID- 10208878
TI  - Up-regulation of liver uncoupling protein-2 mRNA by either fish oil feeding or
      fibrate administration in mice.
AB  - Fish oil feeding showed less obesity in rodents, relative to other dietary oils.
      N-3 fatty acids rich in fish oil and fibrate compounds are peroxisome
      proliferator-activated receptor alpha (PPARalpha) ligands that stimulate beta
      oxidation of fatty acids in liver and are used for treatment of hypertriglycemic
      patients. Since UCP-2, a member of an uncoupling protein family, has been shown
      to express in hepatocytes, the effects of these agents on the expression of UCP2
      mRNA were investigated. C57BL/6J mice were divided into three groups; the first
      group was given a high-carbohydrate diet, and the other two groups were given a
      high-fat diet (60% of total energy) as safflower oil or fish oil for 5 months.
      Safflower oil diet fed mice developed obesity, but those fed fish oil diet did
      not. Therefore, the effects of fish oil feeding on the expression of UCP1, UCP2
      and UCP3 in liver, skeletal muscle (gastrocnemius), white adipose tissue (WAT)
      and brown adipose tissue (BAT) were assessed by Northern blotting. Compared with
      safflower oil feeding, fish oil feeding up-regulated liver UCP2, BAT UCP2 and
      skeletal muscle UCP3 mRNA, while down-regulated WAT UCP2 and BAT UCP3 mRNA. Among
      these alterations, 5-fold up-regulation of liver UCP2 mRNA, relative to
      carbohydrate feeding, was noteworthy. Fenofibrate administration (about 500 mg/kg
      BW/d) for 2 wks also induced liver UCP2 expression by 9-fold. These data
      indicated that fish oil feeding and fibrate administration each up-regulated UCP2
      mRNA expression in liver possibly via PPARalpha and hence each has the potential
      of increasing energy expenditure for prevention of obesity.

PMID- 10208879
TI  - The mouse ortholog of the human SMARCB1 gene encodes two splice forms.
AB  - The human SMARCB1 gene (SWI/SNF-related, matrix-associated, actin-dependent
      regulator of chromatin, subfamily b, member 1, previously named the INI1/hSNF5
      gene) is a tumor suppressor gene located on chromosome 22q11.2 and is inactivated
      in malignant rhabdoid tumors. By using an EST-based approach, we cloned two
      splice forms of the Smarcb1 gene in mouse and a longer splice form of the human
      ortholog. Proteins corresponding to the longer (385 aa) and the shorter (376 aa)
      forms are 100% conserved between human and mouse. Meningiomas and schwannomas are
      tumors frequently deleting various regions on chromosome 22, including the
      SMARCB1 locus. We therefore directly sequenced seven SMARCB1 exons (90% of the
      open reading frame) in search for mutations in 41 meningiomas and 23 schwannomas.
      No inactivating mutations were observed, which suggests that the SMARCB1 gene is
      not involved in the pathogenesis of these tumors.

PMID- 10208880
TI  - Restricted expression pattern of vegf-d in the adult and fetal mouse: high
      expression in the embryonic lung.
AB  - Endothelial growth factors have become the target of intense research since the
      initial discovery of vascular endothelial growth factor (VEGF/VPF). At present,
      VEGF is established as a major inducer of angiogenesis in normal and pathological
      conditions. Recently several new members in the VEGF family have been described;
      VEGF-B/VRF, VEGF-C and VEGF-D. VEGF-D is most closely related to VEGF-C by virtue
      of the presence of N- and C-terminal extensions that are not found in other VEGF
      family members. We have here examined the expression pattern of vegf-d mRNA with
      in situ hybridization in developing and adult mice. This shows a restricted
      expression pattern, with high levels mainly in lung tissue. The expression in
      embryonic lung is upregulated prior to birth. Expression of vegf-d in other
      tissues, as well as in lung tissue of the E14 embryo, was either low or absent.
      This suggests that VEGF-D may be of special relevance for the vascularization of
      lung tissue during the last trimester of fetal development.

PMID- 10208881
TI  - Ca2+ and protein kinase C signaling for histamine and sulfidoleukotrienes
      released from human cultured mast cells.
AB  - Human cultured mast cells (HCMC) release histamine and sulfidoleukotrienes (LTs)
      upon IgE-FcepsilonRI-mediated mast cell activation. We analyzed the Ca2+ and PKC
      signaling in HCMC and compared it to that in rodent mast cells. In HCMC, after
      IgE-mediated stimulation, an elevation of [Ca2+]i and PKC translocation to the
      membrane fraction was observed. As concerns Ca2+ signaling, 1) IgE-mediated
      histamine and LTs release was abolished after Ca2+ depletion, and the
      reconstitution of Ca2+ recovered the release of histamine and LTs. As regards PKC
      signaling, 1) staurosporine inhibited IgE-mediated mediator release. 2) PKC
      downregulated mast cells did not release histamine and LTs. A23187 and PMA
      synergistically potentiated the activation of extracellular-regulated kinase and
      synergistically induced histamine and LTs release. These results demonstrated
      that HCMC might be useful for analysis of the signal transduction pathway for
      mediator release, such as histamine and LTs.

PMID- 10208882
TI  - A two-component tetrachlorohydroquinone reductive dehalogenase system from the
      lignin-degrading basidiomycete Phanerochaete chrysosporium.
AB  - Tetrachloro-1,4-hydroquinone (TClHQ) is an intermediate in the degradation of
      pentachlorophenol by the lignin-degrading basidiomycete Phanerochaete
      chrysosporium. Two enzymes required for the reductive dehalogenation of TClHQ to
      trichlorohydroquinone (TrClHQ) were identified in cell-free extracts of P.
      chrysosporium. In the presence of GSH, a membrane-bound enzyme converted TClHQ to
      the glutathionyl conjugate of TrClHQ (GS-TrClHQ). This membrane-bound glutathione
      transferase was specific for GSH as a cosubstrate. In the second step of the
      reductive dehalogenation reaction, a soluble enzyme fraction converted GS-TrClHQ
      to TrClHQ in the presence of GSH, cysteine, or dithiothreitol. Thus, this second
      enzyme appears to be a GS-conjugate reductase. These two enzyme fractions,
      working in tandem, also reductively dehalogenated TrClHQ and 2,6
      dichlorohydroquinone, which are intermediates in the degradation of chlorophenols
      by this organism.

PMID- 10208884
TI  - Effect of the method of capture on the haematology and blood chemistry of red
      deer (Cervus elaphus).
AB  - Haematological and plasma biochemical constituents can be affected during capture
      and handling operations in wildlife. The present study compares the blood
      constituents of 40 red deer (Cervus elaphus) captured using two different
      methods: 20 were captured by physical means, using long nets and box traps, and
      20 by chemical means, using a mixture of xylazine and ketamine. Significant
      differences were found in the haemogram: red blood cell count, packed cell
      volume, haemoglobin concentration, and segmented neutrophil, lymphocyte, monocyte
      and total leukocyte counts were higher in animals captured by physical means.
      Conversely, the eosinophil count was higher in deer captured using anaesthetic.
      The plasma activity of alanine amino transferase, and the concentrations of
      cholesterol, triglycerides, albumin, alpha-2 globulins, total proteins, sodium
      and chloride, were significantly higher in the group captured by physical means.
      With the exception of the eosinophil count, all the blood constituents which
      presented higher values were in the group of physically captured deer, and thus
      it is necessary to take into account the method of capture when interpretation or
      establishment of reference values is performed.

PMID- 10208883
TI  - Identification of a human Akt3 (protein kinase B gamma) which contains the
      regulatory serine phosphorylation site.
AB  - The family of protein kinases called Akt, protein kinase B (PKB), or related to A
      and C kinase (RAC) have been implicated in numerous biological processes
      including adipocyte and muscle differentiation, glycogen synthesis, glucose
      uptake, apoptosis and cellular proliferation. There are 3 known isoforms of this
      enzyme in mammalian cells (1/alpha, 2/beta and 3/gamma). Akt1 and 2 contain a key
      regulatory serine phosphorylation site in the carboxy-terminal region of the
      protein. However, the reported sequence of the rat Akt3 protein differed
      significantly from this in that it lacked 25 amino acids in the C-terminal
      region, including this key regulatory serine phosphorylation site (Biochem.
      Biophys. Res. Commun. 216, 526-534). In the present studies we show that the
      deduced sequence of human Akt3 contains this serine and that it is phosphorylated
      in response to insulin. These results indicate that human Akt3 is regulated
      similarly to Akt1 and Akt2.

PMID- 10208885
TI  - Studies of endotoxin-dependent fever in pre-pubertal pigs following acute
      activation of the pituitary-adrenocortical axis: towards a new hypothesis of
      fever regulation.
AB  - The possibility that adrenocortical activation might alter the pyretic effects of
      bacterial lipopolysaccharide endotoxin in growing pigs was investigated. In a
      series of four experiments, animals received increasing doses of porcine
      adrenocorticotrophic hormone ACTH (1.5, 4.5, 13.5 IU kg-1) or CRH (7 microg kg
      1), all of which markedly affected cortisol release. Unexpectedly, these
      treatments tended to increase body temperature during the early and middle stages
      of the febrile response, although they did appear to induce an earlier
      deferscence. These results suggest that acute stress may not modify fever induced
      by immunological challenge, although a different situation could obtain during
      chronic stress. Furthermore, a hypothesis of fever regulation is proposed which
      attempts to reconcile the present findings with those from previous studies in
      swine.

PMID- 10208886
TI  - Pulsed-field gel electrophoresis and distribution of the genes zag and fnz in
      isolates of Streptococcus equi.
AB  - Streptococcus equi subsp. equi and subsp. zooepidemicus are important pathogens
      of the equine respiratory tract. Isolates of both subspecies were examined by
      pulsed-field gel electrophoresis (PFGE). With the exception of eight isolates, a
      unique band pattern was displayed for each of the 48 subsp. zooepidemicus
      isolates tested. A method to distinguish isolates of the genetically very
      homogeneous subsp. equi has hitherto not been available, although several methods
      have been tested. By the use of PFGE, 50 isolates of subsp. equi could be divided
      into eleven groups, each with a unique pulsotype. In addition, the recently
      characterised genes encoding the cell-wall proteins ZAG and FNZ of S. equi subsp.
      zooepidemicus strain ZV were shown by Southern blots to be present in all 98
      tested isolates, including the type strains of the two subspecies. Binding assays
      showed that the expression of the two genes clearly differentiate between the two
      subspecies.

PMID- 10208887
TI  - Responses of cattle to two dosages of Brucella abortus strain RB51: serology,
      clearance and efficacy.
AB  - A new brucellosis vaccine, Brucella abortus strain RB51 (SRB51), is currently
      recommended for use as a calfhood vaccine in the US at dosages between 1 x
      10(10)and 3.4 x 10(10)colony-forming units (CFU). The purpose of the study
      reported here was to compare responses to minimal and maximal recommended SRB51
      dosages. Eighteen heifer calves were vaccinated subcutaneously with 1.6 x
      10(10)CFU of SRB51, 3.2 x 10(10)CFU of SRB51, or saline (n = 6 per treatment).
      The vaccine strain was recovered from the superficial cervical lymph node 14
      weeks after vaccination in two of six animals that received 1.6 x 10(10)CFU
      SRB51, but not from any cattle vaccinated with 3.2 x 10(10)CFU SRB51. The higher
      SRB51 dosage stimulated greater antibody titres. Protection against abortion or
      infection following B. abortus strain 2308 (S2308) challenge was similar for both
      SRB51 dosages and greater than resistance of non-vaccinates. The vaccine strain
      was recovered from one heifer and her fetus at necropsy 1 week prior to estimated
      parturition. Data from this study suggests that SRB51 induces similar protective
      immunity across the recommended dosage range. The SRB51 vaccine may persist in
      some cattle into adulthood but the incidence and significance of this persistence
      remains unknown.

PMID- 10208888
TI  - Quantification of the pain and distress responses to castration in young lambs.
AB  - Pain and distress following castration were assessed in lambs using three
      indicators: behaviour, plasma cortisol and mechanical nociceptive thresholds.
      Three castration methods: rubber ring (RR), combined ring and Burdizzo clamp (CM)
      and surgery (SU) were compared. The effects of castration following local
      anaesthetic pre-treatment (LA) and castration performed under general anaesthetic
      (GA) were compared to castration performed with no anaesthetic. This gave a 4 x 3
      x 3 block design i.e. 36 experimental treatments. Six lambs were allocated to
      each treatment i.e. 216 lambs were used in all. SU produced the greatest
      response, followed by RR then CM castration. LA abolished the responses to RR and
      CM castration but had no effect on the response to SU castration. GA did not
      reduce the responses to RR and SU but abolished the rise in mechanical
      nociceptive thresholds and markedly attenuated active pain behaviours in lambs CM
      castrated without anaesthesia. This suggests that the clamping procedure itself
      rather than post-castration pain and distress is responsible for the rise in
      nociceptive thresholds and active pain behaviours in CM castrated lambs.

PMID- 10208889
TI  - Tremorgenic mycotoxins paxilline, penitrem and lolitrem B, the non-tremorgenic 31
      epilolitrem B and electromyographic activity of the reticulum and rumen of sheep.
AB  - The mycotoxic tremorgens penitrem, paxilline and lolitrem B had profound effects
      on electromyographic (EMG) activity of smooth muscle of the reticulorumen in
      conscious sheep, with a similar time course of action to their respective
      characteristic effects on the induction (1 to 2, 15 to 20 and 20 to 30 minutes)
      and the duration (1 to 2, 1 to 2 and 8 to 12 hours) of tremoring. Responses to
      penitrem revealed a greater sensitivity of smooth muscle than skeletal muscle.
      Effects included an inhibition of the vagally-dependent cyclical A and B
      sequences of contraction of the reticulorumen, an increase in their amplitude and
      an excitation of local intrinsic activity contributing to elevated baselines and
      the occurrence of chaotic activity of the reticulum. The excitatory local effects
      were partially blocked by atropine, indicating that stimulation of muscarinic
      cholinoceptors was involved. Increased local activity may mediate a reflex
      inhibition of cyclical contractions. A non-tremorgenic isomer of lolitrem B (31
      epilolitrem B) had no effect on the reticulorumen. The intensity and duration of
      the effects of lolitrem B, up to 12 hours, indicate that severe disruption of
      digestion may occur in animals grazing endophyte-infected pasture.

PMID- 10208890
TI  - Plasma oestrone and oestradiol concentrations throughout gestation in cattle:
      relationship to stage of gestation and fetal number.
AB  - The objectives of the study were to characterise the peripheral plasma oestrone
      (E1) and oestradiol-17beta (E2) concentrations throughout gestation in the cow
      and to correlate this with the stage of gestation and fetal number. Cows (n = 10)
      were equally divided into two groups after non-surgical embryo transfer of in
      vitro matured and in-vitro fertilised (IVM - IVF) embryos; Group 1 received a
      single embryo, Group 2 received twin embryos. Blood was collected about every
      third day from day 0 (day 0 was defined as first day of standing oestrus), then
      daily for the last 10 days of gestation and sampling was stopped one day post
      partum. Plasma E1 concentration exceeded that of E2 throughout gestation in both
      groups of cows. The time trend concentrations of plasma E1 were significantly
      affected by the stage of gestation (P < 0.01) and fetal number (P < 0.01) in the
      last two trimesters of gestation. The time trend concentrations of plasma E2 were
      significantly affected by the stage of gestation (P<0.01) but not foetal number
      (P = 0.09). In both groups there was marked preparturient increase in E1 and E2
      concentrations. Plasma E2 profile between days 10 prepartum to parturition
      paralleled E1 in cows carrying a single foetus but was disparate during the same
      period in the twin-bearing cows. To conclude, our results indicate that although
      plasma E1 concentration was greater than E2 throughout gestation, both were
      related to the stage of gestation and that fetal number was correlated with
      circulating E1 levels in the last two trimesters of gestation.

PMID- 10208891
TI  - Metabolic effects of nitric oxide synthase inhibition during exercise in the
      horse.
AB  - The effect of nitric oxide synthase (NOS) inhibition during exercise on lactate
      production was investigated in five Thoroughbred horses. A standard exercise test
      (SET), consisting of three canters (approximately 55 per cent VO2max), with
      walking and trotting between each canter, was performed twice (control and test,
      in random order) by each horse. Nphi-nitro-L-arginine methyl ester (L-NAME; 20 mg
      kg-1), a competitive inhibitor of NOS, induced a significant increase (P < 0.05)
      in plasma lactate [5.7 (2.9) vs 11.8 (3.8) mmol L-1], which continued to increase
      despite administration of L-arginine, the substrate for NOS. There were no
      differences in cardiac output (Q) or the total body oxygen consumption (VO)
      between each SET. The results show that non-specific inhibition of NOS isoforms
      during exercise in the horse increases plasma lactate concentration, although the
      mechanism/s remain uncertain.

PMID- 10208892
TI  - Apoptosis and mitosis in tumours of the skin and subcutaneous tissues of the dog.
AB  - The presence of apoptotic cell death was evaluated in routinely processed tissue
      samples of 39 neoplasms of the skin and subcutaneous tissues of the dog using the
      method of terminal deoxynucleotidyl transferase (T d T) mediated deoxyuridine-5'
      triphosphate (d UTP)-biotin nick end labelling (TUNEL). The degree of apoptosis
      was related to the frequency of mitosis, an index of cell proliferation. The
      correlation between the apoptotic index (AI), the percentage of positive cells
      after randomly enumerating 1000 cells and the mitotic count (MC), the number of
      mitotic figures in 10 fields at a magnification of 400 times was assessed by the
      Spearman non-parametric correlation test. TUNEL signals were observed in all
      types of tumours as brown products detected in non-pyknotic nuclei, in non
      identifiable rounded structures (so-called apoptotic bodies) and occasionally in
      the cytoplasm, either singly or in combination. An inverse relationship between
      AI and MC was observed in benign tumours, while no correlation was found between
      AI and MC in either malignant or locally invasive tumours. Among benign tumours,
      intracutaneous cornifying epithelioma, fibroma, haemangioma and Schwannoma had
      high AI and low MC, while histiocytomas had low AI and high MC and pilomatrixomas
      low AI and MC. All malignant tumours had low AI and high MC, except for
      fibrosarcomas, which had high AI and MC. Finally, higher heterogeneity was
      observed among locally invasive tumours, as they had high AI and low MC (squamous
      cell carcinomas), and low AI with either low MC (haemangiopericytomas) or high MC
      (basal cell tumours). The classification of the tumours according to their AI
      (>15.8% high and <15.8% low) and MC (>9 high, <9 low) did not reflect the
      clinical behaviour of some tumour types.

PMID- 10208894
TI  - The pharmacokinetics of promethazine after intravenous administration in camels.
AB  - The pharmacokinetics of promethazine were determined in seven camels (Camelus
      dromedarius) after an intravenous dose of 0.5 mg kg body weight.-1 The data
      obtained (median and range) were as follows: the elimination half-life (t1/2
      beta) was 5.62 (2.84-6.51) h; the steady state volume of distribution (Vdss) was
      8.90 (7.10-12.00) L kg-1, total body clearance (CT) was 24.5 (17.22-33.65) ml kg
      1 min-1 and renal clearance (Clr) was 4.81 (1.97-5.48) ml kg-1 min-1.

PMID- 10208893
TI  - The response of Nigerian West African Dwarf goats to experimental infections with
      Haemonchus contortus.
AB  - One option for controlling haemonchosis in warm pastoral regions is improvement
      of resistance by selective breeding. Variation in acquired immunity to H.
      contortus and immunological correlates of infection were studied in West African
      Dwarf (WAD) goats. Following exposure to 5000 L3, 63 per cent of the inoculum
      established but 77 per cent of established worms were expelled by week 5. All
      infected animals were anaemic (day 14). When exposed to 2000L3, 36 per cent of
      the inoculum was still present (day 35) with no loss by day 49. Persisting
      primary infection worms survived a superimposed challenge (day 35), but their
      growth was slowed and resistance to challenge was significant. Most goats showed
      eosinophilia and parasite-specific IgG responses to primary infection, but only
      eosinophilia increased after challenge. No consistent associations were found
      between parasite burden and any immunological measures of infection, but parasite
      egg counts showed considerable variation. Overall, our results suggest that
      resistant genotypes exist among the WAD goat population.

PMID- 10208895
TI  - Investigation into avian pneumovirus persistence in poults and chicks using
      cyclosporin A immunosuppression.
AB  - One-day-old poults or two-week old chicks were infected oculonasally with avian
      pneumovirus. Cloacal swabs were collected for virus isolation as were selected
      tissues (Harderian gland, turbinates, trachea, lungs and kidneys) from birds
      killed at regular intervals up to 33 days post infection (p.i.) for poults, and
      up to 40 days p. i. for chicks. In an attempt to induce virus re-excretion, the T
      cell-suppressor cyclosporin A (CSA) was given for 12 days starting from three
      weeks p.i. in poults and from four weeks p.i. in chicks. Birds were sampled for
      virus isolations up to day 12 post CSA treatment. Virus was recovered only up to
      day nine p.i. in poults, and day five p.i. in chicks during the acute phase of
      the infection. Despite T-cell suppression, there was no evidence of re-excretion
      of the virus, and hence no evidence for the persistence of virus in the tissues
      examined.

PMID- 10208896
TI  - Monoclonal antibody sandwich immunoassay detection of coproantigen to evaluate
      the efficacy of treatment in natural ovine fasciolosis.
AB  - The monoclonal antibody-based sandwich immunoassay (mAb Sandwich ELISA) was used
      to evaluate the effectiveness of triclabendazole treatment by the detection of
      coproantigens in Fasciola hepatica naturally infected sheep. Twelve sheep (2 to 5
      years of age) were separated into two groups. The first group (three sheep)
      remained untreated; the other group (nine sheep) was treated with a single dose
      of 5% triclabendazole at 10 mg kg-1 of body weight. All but one of the treated
      group had negative optical density values (OD492) after two weeks of treatment,
      while seven sheep intermittently shed eggs during the course of the study. In all
      but one of the treated sheep, no F. hepatica infection; the one positive ELISA in
      5th week after treatment according to the mAb Sandwich, had one fluke in the
      liver. The results of the parasitological examinations, as well as OD492 values
      obtained by the mAb Sandwich ELISA for the detection of coproantigens are
      described. The findings at necropsy, of the treated group in comparison to the
      untreated group are shown. The mAb Sandwich ELISA could be a useful and accurate
      method with which to monitor the efficacy of flukicides in F. hepatica natural
      infections.

PMID- 10208914
TI  - Immunopathogenesis of Dengue hemorrhagic fever.

PMID- 10208915
TI  - Sites of simian foamy virus persistence in naturally infected African green
      monkeys: latent provirus is ubiquitous, whereas viral replication is restricted
      to the oral mucosa.
AB  - Foamy viruses (FV), retroviruses of the genus Spumavirus, are able to infect a
      wide variety of animal species and replicate in nearly all types of cultured
      cells. To identify the cells targeted by FV in the natural host and define the
      sites of viral replication, multiple organs of four African green monkeys
      naturally infected with simian FV type 3 were investigated for the presence of FV
      proviral DNA and viral transcripts. All organs contained significant amounts of
      FV proviral DNA. In addition to proviruses containing the complete transactivator
      gene taf, proviral genomes carrying a specific 295-bp deletion in the taf gene
      were detected in all monkeys. As in the case of human foamy virus the deletion
      leads to the formation of the bet gene that is regarded to be instrumental in the
      regulation of viral persistence. FV RNA was detected by RT-PCR and in situ
      hybridization only in the oral mucosa of one monkey. No other samples contained
      detectable levels of viral transcripts. Histopathological changes were not
      observed in any of the tissue samples analyzed. Our results show that the natural
      history of FV is characterized by latent infection in all organs of the host and
      by minimal levels of harmless viral replication in the oral mucosa. The broad
      host cell range in vivo further encourages the development of FV-derived vectors
      for therapeutic gene delivery.

PMID- 10208916
TI  - Hyaluronan synthesis in virus PBCV-1-infected chlorella-like green algae.
AB  - We previously reported that the chlorella virus PBCV-1 genome encodes an
      authentic, membrane-associated glycosyltransferase, hyaluronan synthase (HAS).
      Hyaluronan, a linear polysaccharide chain composed of alternating beta1,4
      glucuronic acid and beta1, 3-N-acetylglucosamine groups, is present in
      vertebrates as well as a few pathogenic bacteria. Studies of infected cells show
      that the transcription of the PBCV-1 has gene begins within 10 min of virus
      infection and ends at 60-90 min postinfection. The hyaluronan polysaccharide
      begins to accumulate as hyaluronan-lyase sensitive, hair-like fibers on the
      outside of the chlorella cell wall by 15-30 min postinfection; by 240 min
      postinfection, the infected cells are coated with a dense fibrous network. This
      hyaluronan slightly reduces attachment of a second chlorella virus to the
      infected algae. An analysis of 41 additional chlorella viruses indicates that
      many, but not all, produce hyaluronan during infection.

PMID- 10208917
TI  - Replication and budding of simian immunodeficiency virus in polarized epithelial
      cells.
AB  - Simian immunodeficiency virus (SIV) infection of primates provides an important
      model for infection of humans by HIV. Since mucosal epithelium is likely to be an
      important portal of entry, we decided to study aspects of the interaction of SIV
      with epithelial cells. SIV was shown to produce virus efficiently in polarized
      epithelial cells (Vero C1008) transfected with SIVmac239 proviral DNA. The virus
      titer in the epithelial cell culture fluid reached 10(3) TCID50/ml at day 3
      posttransfection. Initially after transfected epithelial cells were plated on a
      permeable membrane, virus budded at both the apical and the basolateral domains.
      However, after the cells formed a tight monolayer, 95-100% of the virus particles
      budded basolaterally, as assessed by release of p27 antigen into the fluid above
      and below the monolayer. This finding was confirmed by electron microscopy, which
      showed that the mature virus budded basolaterally in polarized cells. After
      introduction of the CD4 gene into Vero cells by a retrovirus vector, polarizable
      cells were able to be infected by cell-free SIVmac239 virus. The virus titer
      reached 10(4) TCID50/ml in culture fluid and virions also budded basolaterally,
      the same as the virus from transfected cells. Two viruses (SIVmac1A11 and
      SIVmac251) that contain truncated TMgp28 instead of TMgp41 also budded
      basolaterally. Furthermore, we found that HIV-1 with full-length or truncated
      TMgp41 also budded basolaterally.

PMID- 10208918
TI  - Reovirus type 3 clone 9 increases interleukin-1alpha level in the brain of
      neonatal, but not adult, mice.
AB  - Reovirus Type 3 clone 9 (T3C9)-induced lethal encephalitis is age dependent. We
      examined the effects of T3C9 inoculated into neonatal and adult mice by
      intracerebral, intramuscular, or peroral routes and the effect of
      lipopolysaccharide (LPS) on IL-1alpha levels in the blood and the brain. In
      parallel, we measured mice survival to T3C9 challenge, primary replication, and
      growth in and spread to the brain. The results show that T3C9 infection increased
      IL-1alpha only in the brain of neonatal mice, whereas LPS enhanced IL-1alpha in
      the brain and in the blood in both neonatal and adult mice. In neonatal mice, a
      T3C9-induced IL-1alpha increase coincided with viral replication-induced nervous
      tissue injury and preceded death. Anti-IL-1alpha antibody partially protected
      neonatal mice against T3C9 peroral challenge, further suggesting that this
      cytokine is involved in the mechanisms leading to lethal encephalitis. In adult
      mice, T3C9 was not lethal and did not modify IL-1alpha levels although it slowly
      replicated in nervous tissues when inoculated directly into the brain. Together,
      these results suggest that differences in nervous tissue response to T3C9
      replication between newborn and adult mice could account in part for the age
      dependent susceptibility to T3C9-induced lethal encephalitis.

PMID- 10208919
TI  - Two domains within the adenovirus type 12 E1A unique spacer have disparate
      effects on the interaction of E1A with P105-Rb and the transformation of primary
      mouse cells.
AB  - Transformation of primary rodent cells by functions of the adenovirus type 12
      (Ad12) early region 1 (E1) is reduced severalfold compared with transformation by
      E1 of Ad2. We analyzed whether the unique spacer region of Ad12 E1A that borders
      the conserved region (CR) 2 and represents an oncogenic determinant of Ad12 E1A
      is involved in this impaired transformation property, putatively by modulating
      transformation-relevant biological E1A functions. We show that a mutant (E1ASpm1)
      that lacks 12 amino-terminal residues of the spacer binds p105-Rb and p130 as
      Ad12 E1A wild type (E1Awt), whereas a second spacer mutant (E1ASpm2) that lacks
      an adjacent stretch of six alanines exhibits highly reduced binding to p105-Rb.
      The binding of this mutant to the p130 pocket protein is, however, little
      impaired. E1ASpm1 diminishes the formation of the p105-Rb-E2F complex more
      efficiently than E1Awt or, least efficient, E1ASpm2. These properties of the
      spacer mutants to target and to disintegrate the p105-Rb-E2F complex correspond
      with their ability to transform primary mouse cells in combination with E1B:
      E1ASpm1 (plus Ad12 E1B)-transfected cells could be easily established as cell
      lines, comparable to Ad12 E1Awt- or Ad2 E1Awt-transfected cells. In contrast,
      cells transfected with E1ASpm2 or Ad12 E1AdelCR2 (lacking the entire CR2) died
      within 6-10 weeks after replating, although foci were formed in all cases. Of
      note, the E1ASpm1-transformed cells grow as fast as the Ad2 E1Awt-transformed
      cells, with a doubling rate of 15 h, whereas the doubling of the Ad12 E1Awt
      transformed cells takes approximately 120 h. Moreover, in the established cell
      lines, the affinity of E1ASpm1 to p105-Rb was higher than with that of E1Awt. Our
      data suggest the presence of a transformation-suppressing domain within the
      carboxyl-terminal 12 residues of the Ad12 E1A-unique spacer, whereas the
      hydrophobic stretch of six alanines in the spacer is required for stable
      transformation.

PMID- 10208920
TI  - Packaging of AeDNV-GFP transducing virus by expression of densovirus structural
      proteins from a sindbis virus expression system.
AB  - Genetic recombination resulting in the production of wild-type infectious virus
      is an obstacle in the current system for producing densovirus transducing
      particles. In order to eliminate this problem, a double subgenomic Sindbis virus
      (TE/3'2J/VP) was engineered that expresses the structural proteins (VPs) of Aedes
      densonucleosis virus (AeDNV) from the second subgenomic promoter. Expression of
      AeDNV VPs from TE/3'2J/VP was confirmed by Northern analysis of RNA from infected
      C6/36 (Aedes albopictus) cells and by indirect immunofluorescence in infected
      C6/36 cells and BHK-21 cells. TE/3'2J/VP was used to infect C6/36 cells
      transfected with p7NS1-GFP, a plasmid expressing the nonstructural genes of AeDNV
      and green fluorescent protein (GFP) as a reporter gene. This infection resulted
      in the production of AeDNV-GFP transducing virus, which is infectious to C6/36
      cells and Aedes aegypti larvae, as determined by GFP expression. The TE/3'2J/VP
      packaging system produced titers of transducing virus comparable to those
      produced by the standard two-plasmid method. The possibility of recombination
      resulting in wild-type infectious virus in transducing densovirus stocks was
      eliminated by employing an RNA virus expression system to supply AeDNV structural
      proteins.

PMID- 10208921
TI  - Transduction of Aedes aegypti mosquitoes with vectors derived from Aedes
      densovirus.
AB  - Aedes densovirus (AeDNV)-based constructs that express green fluorescent protein
      (GFP) from either the P7 or the P61 promoter were made. The construct in which
      GFP protein was expressed as a fusion protein to the C-terminus of NS1 (NS1-GFP)
      showed the highest level of GFP expression. This hybrid NS1-GFP protein preserved
      the biological functions of the parental proteins: it showed GFP fluorescence, it
      stimulated expression from the virus promoters, and it facilitated rescue and
      replication of the cloned AeDNV genome. Similar to NS1, the hybrid NS1-GFP
      localized in the nucleus predominantly in a punctate pattern. Transducing virus
      particles carrying the NS1-GFP gene infected mosquito larvae. Expression of GFP
      was detected as early as 48 h postinfection and in larval and pupal stages.
      Midgut, hindgut, and Malpighian tubule cells expressed GFP soon after
      transduction. However, the anal papillae were the most commonly infected organ
      system. The anal papillae are syncytia and regulate ion concentration in the
      hemolymph of mosquito larvae, and they might be a novel route of mosquito larvae
      infection with densoviruses.

PMID- 10208922
TI  - Identification of MaTu-MX agent as a new strain of lymphocytic choriomeningitis
      virus (LCMV) and serological indication of horizontal spread of LCMV in human
      population.
AB  - In this study we elucidated the molecular character of MaTu-MX, previously
      described as an unusual transmissible agent. Amino acid sequencing of peptides
      generated from a 58-kDa MX-related protein purified from MaTu human carcinoma
      cells allowed us to identify it as a nucleoprotein (NP) of lymphocytic
      choriomeningitis virus (LCMV). Northern blot analysis detected LCMV-specific RNAs
      in MaTu cells. Comparative immunoprecipitations showed cross-reactivity between
      NP of LCMV strain WE and MX NP. Using RT-PCR, we have cloned MX NP cDNA.
      According to sequence comparison, MX LCMV is as closely related to both LCMV
      strains WE and Armstrong as these strains are to one another. Based on this
      finding we propose that MX is a new strain of LCMV. We also showed that the
      stability of MX NP in MaTu cells is very high and that the virus is transmissible
      by cell-to-cell contact or by cell-free extract to human HeLa and monkey Vero
      cells, but not to human AGS, canine MDCK, mouse NIH 3T3, and hamster CHO cells.
      Finally, employing MX LCMV NP in immunoprecipitation and solid-phase
      radioimmunoassay, we found 37.5% prevalence of anti-LCMV antibodies in human
      sera, suggesting possible horizontal spread of the virus in the human population.

PMID- 10208923
TI  - Transcriptional analysis of human herpesvirus-8 open reading frames 71, 72, 73,
      K14, and 74 in a primary effusion lymphoma cell line.
AB  - We examined the transcription and splicing of open reading frames (ORFs) 71 (K13)
      74 of human herpesvirus-8 (HHV-8) in the primary effusion lymphoma cell line BCP
      1 (latently infected with HHV-8), using a combination of NORTHERN blot analysis,
      RT-PCR, and rapid amplification of cDNA ends (PCR-RACE). The three genes encoded
      by ORFs 71, 72, and 73 [viral FLICE inhibitory protein (v-FLIP), v-cyclin, latent
      nuclear antigen (LNA)] are transcribed from a common transcription start site in
      BCP-1 cells uninduced (latent) or induced (lytic) with n-butyrate. The resulting
      transcript is spliced to yield a 5.32-kb message encoding LNA, v-cyclin, and v
      FLIP and a 1.7-kb bicistronic message encoding v-cyclin and v-FLIP. The two genes
      encoded by ORFs K14 and 74 (v-Ox2 and v-GPCR) are transcribed as a 2.7-kb
      bicistronic transcript that is induced with n-butyrate. A small (149-bp) intron
      is spliced from the intragenic noncoding region immediately before the v-GPCR
      initiating codon. Examination of sequence elements in the promoter of the LNA/v
      cyclin/v-FLIP operon revealed TAATGARAT and Octamer binding motifs characteristic
      of herpesvirus immediate-early genes. Sequence elements in the v-Ox2/v-GPCR
      promoter included AP1 and Zta-like (EBV Zebra transactivator) binding motifs
      consistent with the n-butyrate induction of this operon.

PMID- 10208924
TI  - Identification of a human immunodeficiency virus type 1 that stably uses
      tRNALys1,2 rather than tRNALys,3 for initiation of reverse transcription.
AB  - HIV-1 virions contain approximately equal amounts of tRNALys,3 and tRNALys1,2,
      yet tRNALys,3 has been found to be exclusively used for initiation of reverse
      transcription. Since previous studies have shown that even if the primer binding
      site (PBS) was mutated to be complementary to tRNALys1,2, the virus did not
      stably use tRNALys1,2 to initiate reverse transcription, the virus must have
      evolved a mechanism for the exclusive use of tRNALys,3 to initiate reverse
      transcription. To investigate how HIV-1 discriminates tRNALys1,2 from tRNALys,3
      for initiation of reverse transcription, two proviral genomes that contain
      nucleotide changes in U5 and a PBS to be complementary to regions of tRNALys1,2
      were constructed. One genome contains 5 [HXB2(L12-AC)] nucleotides while another
      contains 15 [HXB2(L12-ACgg)] nucleotides in U5 complementary to the anticodon
      region of tRNALys1,2. Viruses derived from the transfection of the proviral
      genomes were infectious in SupT1 cells. Analysis of the endogenous reverse
      transcription reactions from viruses derived from HXB2 (L12-AC) and HXB2 (L12
      ACgg) obtained from transfection revealed that both exclusively used tRNALys1,2
      to initiate reverse transcription. Following extensive in vitro culture, though,
      sequence analysis of proviral genomes revealed that while the virus derived from
      HXB2(L12-AC) stably maintained a PBS complementary to tRNALys1,2, the virus
      derived from HXB2 (L12-ACgg) had reverted back to contain a PBS complementary to
      tRNALys,3. RNA modeling of the U5-PBS of the genome from HXB2(L12-AC) supports
      the conclusion that the fine specificity for discrimination between tRNALys,3 and
      tRNALys1,2 for use as a primer for HIV-1 reverse transcription resides in the
      structure of the U5-PBS region of the viral genome.

PMID- 10208925
TI  - Role of interferon and interferon regulatory factors in early protection against
      Venezuelan equine encephalitis virus infection.
AB  - To investigate the role of type I interferon (IFN) and its regulatory transacting
      proteins, interferon regulatory factors (IRF-1 and IRF-2), in early protection
      against infection with virulent Venezuelan equine encephalitis virus (VEE), we
      utilized mice with targeted mutations in the IFN-alpha/beta receptor, IRF-1, or
      IRF-2 genes. IFN-alpha/beta-receptor knockout mice are highly susceptible to
      peripheral infection with virulent or attenuated VEE, resulting in their death
      within 24 and 48 h, respectively. Treatment of normal macrophages with anti-IFN
      alpha/beta antibody prior to and during infection with molecularly cloned
      virulent VEE resulted in increased VEE replication. However, treatment with high
      doses of IFN or IFN-inducing agents failed to alter percentage mortality or
      average survival times in mice challenged with a low dose of virulent VEE. In IRF
      1 and IRF-2 knockout mice (IRF-1(-/-) and IRF-2(-/-)), the 100% protection
      against virulent VEE that is conferred by attenuated VEE within 24 h in control
      C57BL/6 mice was completely absent in IRF-2(-/-) mice, whereas 50% of IRF-1(-/-)
      mice were protected. IRF-2(-/-) mice were deficient in clearing VEE virus from
      the spleen and the brain compared to the heterozygous IRF-2(+/-) knockout or
      C57BL/6 (+/+) mice. Furthermore, a distinct pattern of histopathological changes
      was observed in brains of IRF-2(-/-) mice after VEE exposure. Taken together,
      these findings imply that the altered immune response in IRF-1 and IRF-2 knockout
      mice results in altered virus dissemination, altered virus clearance, and altered
      virus-induced pathology. Thus, type I interferon, as well as IRF-1 and IRF-2,
      appears to play an important and necessary role in the pathogenesis of, and
      protection against, VEE infection.

PMID- 10208926
TI  - Characterization of early gene transcripts of molluscum contagiosum virus.
AB  - Molluscum contagiosum virus (MCV), a member of the family Poxviridae, replicates
      well in vivo but cannot be propagated in cell culture. The coding capacity of the
      MCV genome was previously determined by DNA nucleotide sequence analysis. The
      objective of the present study was to establish experimental systems for the
      identification and characterization of early MCV gene transcripts. MCV mRNA was
      obtained in three ways: (1) MCV early mRNA was synthesized in vitro using
      permeabilized virions, (2) MCV mRNA was extracted from MCV-infected skin tissue,
      and (3) MCV mRNA was extracted from MCV-infected human embryonic fibroblasts.
      RNA/DNA hybridization experiments showed significant early transcriptional
      activity in two parts of the MCV genome. Transcripts of 11 early MCV genes
      located in these parts of the genome, including two subunits of the MCV DNA
      dependent RNA polymerase (mc077R and mc079R), the MCV poly(A)+ polymerase gene
      (mc076R), and the MCV MHC class I homolog (mc080R), were detected in reverse
      transcription-polymerase chain reaction experiments. Total RNA obtained from MCV
      infected skin tissue was used to confirm these results. Three MCV early
      transcripts, mc002L, mc004.1L, and mc005L, produced distinct bands on rapid
      amplification of their 3' ends (3' RACE). The 5' mapping of transcription start
      sites of MCV open reading frames (ORFs) mc002L, mc004.1L, mc005L, and mc148R
      revealed that the MCV RNA polymerase transcription start sites are consistently
      located between 11 and 13 nucleotides downstream of the early MCV consensus
      promoter signal. When cDNA from both 5' and 3' mapping experiments was analyzed,
      MCV ORFs mc004. 1L and mc005L were found to be transcribed as a single
      bicistronic mRNA. The transcript from MCV ORF mc066L, encoding a glutathione
      peroxidase, was detected in in vitro synthesized MCV mRNA as well as in total RNA
      from MCV-infected human embryonic fibroblasts and MCV-infected skin. This
      indicates that despite the lack of an early MCV consensus promoter signal
      immediately proximal to the start codon, this particular gene is transcribed
      early during MCV infection.

PMID- 10208927
TI  - Phosphorylation of nonstructural 5A protein of hepatitis C virus: HCV group
      specific hyperphosphorylation.
AB  - We previously showed that two proteins with molecular weights of 56 and 58 kDa
      are produced from nonstructural protein 5A (NS5A) derived from hepatitis C virus
      (HCV)-1b genotype. The 56-kDa protein is phosphorylated at serine residues in
      NS5A, including those located in the C-terminal region of NS5A, while the 58-kDa
      protein, the hyperphosphorylated form of the 56-kDa protein, is phosphorylated at
      serine residues in the central region. This hyperphosphorylation is dependent on
      the presence of HCV NS4A protein. To clarify whether NS4A-dependent
      phosphorylation also occurs in other HCV genotypes, phosphorylation of NS5A was
      analyzed by two-dimensional gel electrophoresis. Here, we report that NS5A from
      the HCV-2a genotype was phosphorylated. However, hyperphosphorylation of NS5A
      occurs in the HCV-1b genotype but not in the -2a genotype. This result suggests
      that modification of NS5A phosphorylation reflects the virological features of
      HCV and that there are physiological differences in the roles of differently
      phosphorylated NS5A between HCV genotypes.

PMID- 10208928
TI  - The acidic region and conserved putative protein kinase C phosphorylation site in
      Nef are important for SIV replication in rhesus macaques.
AB  - Variants of the pathogenic SIVmac239 clone with changes in Nef were analyzed to
      assess the functional relevance of two highly conserved regions in Nef in vitro
      and in vivo. Changes in a region with an acidic charge (Aci-Nef), or a potential
      protein kinase C phosphorylation site (PKC-Nef), impaired the ability of Nef to
      down-regulate CD4 and MHC class I surface expression and to alter CD3-initiated
      signal transduction in Jurkat T cells. The Aci-Nef, but not the PKC-Nef,
      associated with the previously described p65 phosphoprotein. SIV containing Aci
      Nef, but not SIV containing PKC-Nef, showed reduced infectivity and replication
      in cell culture systems. One of two rhesus macaques infected with the PKC-Nef
      mutant virus showed rapid reversion and progressed to disease. In the second
      animal no reversions and nonprogressive infection was observed. In one of two
      macaques infected with the Aci-Nef variant, the mutations were stable during the
      first 40 weeks after infection. Thereafter, variants evolved in which up to six
      of the eight mutated positions in Nef were reverted and functional activity in
      vitro was partially restored. These changes occurred concomitantly with
      increasing viral load and disease progression. The second animal infected with
      the Aci-Nef variant showed no reversions and remained asymptomatic. Our study
      suggests that the acidic region and conserved PKC phosphorylation site in Nef are
      important for SIV replication in rhesus macaques and for several in vitro Nef
      functions. An almost wild-type activity in in vitro infectivity and replication
      assays seems insufficient to confer a full nef-positive phenotype in vivo.

PMID- 10208929
TI  - Analysis of the steps involved in Dengue virus entry into host cells.
AB  - The initial steps of dengue viral entry have been divided into adsorption and
      penetration using acid glycine treatment to inactivate extracellular virus after
      attachment to baby hamster kidney (BHK) cells but prior to penetration. First, we
      showed that virus infection was accomplished within 2 h after adsorption. Second,
      the assay was used to examine the properties of dengue envelope E protein
      specific monoclonal antibodies (MAbs), lectins, and heparin. We found that three
      MAbs, 17-2, 46-9, and 51-3, may neutralize dengue 2 virus (DEN-2) through
      inhibition of not only viral attachment but also of penetration. However, one
      MAb, 56-3.1, interfered specifically with attachment. Therefore, the functional
      domains of E protein involved in attachment and penetration may be different.
      Moreover, studies with lectins indicated that carbohydrates, especially alpha
      mannose residues, present on the virion glycoproteins may contribute to binding
      and penetration of the virus into BHK and mosquito C6/36 cells. Finally, virus
      infectivity was inhibited by heparin through its blocking effects at both virus
      attachment and penetration. This suggests that cell surface heparan sulfate
      functions in both viral attachment and penetration of DEN-2 virus. In conclusion,
      our results further elucidated some aspects of the dengue virus entry process.

PMID- 10208930
TI  - Resistance to herpetic stromal keratitis in immunized B-cell-deficient mice.
AB  - This study evaluates the role of antibody as an indicator of immunity to ocular
      challenge with herpes simplex virus (HSV). Two genotypes of mice, BALB/c or
      BALB/c with mu-chain knockout (muK/O; which lack functional B cells), were
      immunized systemically either with nonvirulent infectious virus or with a
      eukaryotic expression plasmid encoding glycoprotein B (gB). Whereas naive muK/O
      mice were 10- to 100-fold more susceptible to HSV infection than BALB/c mice,
      following immunization both groups showed similar levels of resistance to ocular
      challenge. Thus both HSV-immunized groups cleared virus within 3 days and showed
      no signs of ocular lesions. gB DNA-immunized mice cleared virus less rapidly (5
      days), and the incidence of lesions was 10 and 25% in BALB/c and muK/O mice,
      respectively. Since muK/O mice failed to produce detectable anti-HSV antibody,
      the mechanism of rapid viral removal was assumed to have a T cell basis. However,
      T cells would likely not mediate any protection directly since such cells were
      absent in infected corneas during clearance. A likely mechanism of immunity could
      involve innate defenses, perhaps enhanced by the action of cytokines released
      from antigen-reactive CD4+ cells in vascularized tissue adjacent to the cornea.
      Thus an abrupt inflammatory response consisting principally of neutrophils
      occurred in the corneal stroma in immune mice, and this subsided when virus
      disappeared. These data reveal that even though the deficiency in generating
      antibody renders mice more susceptible to HSV infection, once primed, resistance
      to disease expression is mediated solely by the cellular components and their
      products.

PMID- 10208931
TI  - Antigenic heterogeneity of the hepatitis C virus NS4 protein as modeled with
      synthetic peptides.
AB  - The effect of sequence heterogeneity on the immunologic properties of two strong
      antigenic regions of the hepatitis C virus (HCV) NS4 protein was studied by using
      a set of 443 overlapping 20-mer synthetic peptides. One antigenic region
      comprising the cleavage site between NS4a and NS4b (region 5-1-1) was modeled
      with peptides derived from 73 different known sequences, representing HCV
      genotypes 1-6. The other antigenic region, designated region 59 and located at
      the C-terminus of the NS4b protein, was modeled with peptides from 7 known
      sequences representing genotypes 1-3. All peptides were tested for antigenic
      reactivity by enzyme immunoassay with a panel of anti-HCV-positive serum
      specimens representing genotypes 1-5. The data demonstrated that immunoreactive
      peptides fell into two groups. One group, represented by N-terminal peptides,
      demonstrated genotype-independent immunoreactivity; the other group, from the
      central part of region 5-1-1, showed strict genotype specificity. Nineteen
      peptides from the genotype-independent group strongly immunoreacted with a wide
      range of serum samples containing antibodies to all 5 HCV genotypes. Twenty-five
      peptides from the genotype-specific group were found to strongly react with serum
      containing antibodies only to the genotype from which the peptides were derived.
      Similar to the N-terminal part of region 5-1-1, peptides derived from region 59
      did not show genotype-specific immunoreactivity. Some peptides derived from the
      central part of region 59 showed very strong and broad antigenic reactivity.
      Thus, after examining two antigenic regions of the NS4 protein, we identified
      short sequences that can be used for the efficient detection of either genotype
      independent or genotype-specific HCV antibodies.

PMID- 10208932
TI  - Bovine herpesvirus 1-induced apoptotic cell death: role of glycoprotein D.
AB  - Bovine herpesvirus 1 (BHV-1) induces apoptotic cell death in peripheral blood
      mononuclear cells and in bovine B lymphoma (BL-3) cells. Attachment but not
      penetration of BHV-1 is necessary to induce apoptosis in target cells, suggesting
      that one or more BHV-1 envelope glycoproteins could be involved in the activation
      of the apoptotic process. In the present study, we demonstrate that, although BHV
      1 virions devoid of glycoprotein D (BHV-1 gD-/-) still bind to BL-3 cells, they
      are no longer able to induce apoptosis. In contrast, virions that contain
      glycoprotein D (gD) in the viral envelope but do not genetically encode gD (BHV-1
      gD-/+) induce a level of apoptosis comparable to that produced by wild-type (wt)
      BHV-1. In addition, monoclonal antibodies directed against gD, but not against gB
      or gC, strongly reduced the high levels of apoptosis induced by BHV-1. These
      observations demonstrate that the induction of apoptosis is directly due to BHV-1
      viral particles harboring gD in the viral envelope. Interestingly, binding of
      affinity-purified gD to BL-3 cells did not induce apoptosis but inhibited the
      ability of wt BHV-1 to induce apoptosis. Altogether, these results provide
      evidence for the direct or indirect involvement of gD in the mechanism by which
      BHV-1 induces apoptosis.

PMID- 10208933
TI  - Induction of CD95 (Fas) and apoptosis in respiratory epithelial cell cultures
      following respiratory syncytial virus infection.
AB  - Respiratory syncytial virus (RSV) infection is associated with epithelial cell
      death and vigorous inflammation. In mouse models, and in immunosuppressed
      patients, CD8(+) T cells are necessary for RSV clearance. In vitro, RSV has been
      shown to induce expression of several proteins on the respiratory epithelial
      cell, including RSV proteins, ICAM-1, and MHC class I, that can potentially
      interact with CD8(+) T cells in initiating apoptosis of the target cell. One
      mechanism of T-cell-directed cell death is the interaction of FasL on the CD8(+)
      T lymphocytes and Fas expressed on the target cell. In order to determine the
      ability of RSV to induce Fas on the respiratory epithelium, we studied the RSV
      infection of a human respiratory epithelial cell line (A549) in vitro. Fas mRNA
      and protein levels are increased two-to-fourfold following RSV infection, and
      transcriptional upregulation of Fas was demonstrated using promoter/reporter gene
      constructs. RSV infection directly resulted in cellular apoptosis, and the
      frequency of apoptotic cells was further increased by cross-linking with
      antibodies to Fas. These data demonstrate that RSV infection induces cellular
      apoptosis and suggest that interactions of surface Fas with T cells may further
      augment this process in vivo.

PMID- 10208934
TI  - HIV-1 Nef plays an essential role in two independent processes in CD4 down
      regulation: dissociation of the CD4-p56(lck) complex and targeting of CD4 to
      lysosomes.
AB  - Human immunodeficiency virus type 1 (HIV-1) Nef down-regulates CD4 by triggering
      rapid endocytosis of cell surface CD4. To better understand how Nef induces CD4
      down-regulation, we generated a series of Nef mutants with small in-frame
      deletions in the coding region. Three classes of mutants were obtained. The first
      class produces neither CD4 down-regulation nor dissociation of the CD4-p56(lck)
      complex. The second class induces CD4 down-regulation in cells lacking p56(lck)
      expression, but not in cells with p56(lck);these mutants fail to dissociate CD4
      from p56lck. These results show that Nef-mediated CD4 dissociation from p56(lck)
      is important for CD4 down-regulation. The third class of mutants is able to
      dissociate the CD4-p56(lck) complex but fails to down-regulate surface CD4;
      internalized CD4 molecules are recycled back to the cell surface. This result
      suggests that Nef diverts the CD4 recycling pathway to a degradative pathway. We
      also demonstrate that Nef associates with phosphatidylinositol-3-kinase (PI3K)
      activity, which is known to be involved in several aspects of membrane
      trafficking. However, Nef mutants that cause internalized CD4 to be recycled do
      not associate with PI3K activity; thus Nef-associated PI3K activity might be
      involved in the latter process of targeting CD4 to a degradative pathway. We
      conclude that HIV-1 Nef plays a critical role in multiple processes in CD4 down
      regulation: (i) disrupting the CD4-p56(lck) complex on the cell surface to allow
      CD4 internalization and (ii) diverting the internalized CD4 to a lysosomal
      pathway for its degradation, likely through a PI3K activity.

PMID- 10208935
TI  - Channel catfish virus gene 50 encodes a secreted, mucin-like glycoprotein.
AB  - Cells infected with the wild-type (WT) strain of channel catfish virus (CCV)
      secreted a glycoprotein with an apparent molecular mass (MM) superior to 200 kDa
      into the culture medium. This protein, designated gp250, was the sole viral
      glycoprotein detected in the culture medium after [3H]mannose labeling of the
      infected cells. When cells were infected with the attenuated V60 strain, a
      glycoprotein of 135 kDa (designated gp135) was detected instead of gp250. Because
      WT gene 50 is predicted to encode a secreted, mucin-type glycoprotein, we
      expressed this gene transiently and detected a glycoprotein of the same apparent
      MM as gp250 in the culture medium of transfected catfish cells. The increased
      mobility in SDS-PAGE of the secreted V60 glycoprotein correlated with the
      presence of a major deletion in V60 gene 50. Therefore, we concluded that gp250
      in the WT and gp135 in the V60 strains are both likely encoded by gene 50. An
      important shift in the relative mobility of gp250 in SDS-PAGE was observed after
      tunicamycin treatment of infected cells labeled with [3H]glucosamine, confirming
      the presence of N-linked sugars on gp250. We observed variations in the size of
      PCR products derived from gene 50 amplification in three different field
      isolates. Such genetic variations are a characteristic feature of mucin genes and
      are linked to crossing-over events between internal repeated sequences, such as
      those present in gene 50.

PMID- 10208936
TI  - Role of the leukocyte function antigen-1 conformational state in the process of
      human immunodeficiency virus type 1-mediated syncytium formation and virus
      infection.
AB  - Human immunodeficiency virus type 1 (HIV-1)-mediated syncytium formation is
      recognized as being highly dependent on intercellular adhesion molecule (ICAM)-1
      leukocyte function-associated molecule 1 (LFA)-1 interaction, whereas the process
      of infection with cell-free virions is independent of such complementary
      interaction. Our group has recently demonstrated that an antibody-mediated
      induction of the high affinity state of LFA-1 for ICAM-1 renders target T cells
      more prone to HIV-1-dependent syncytium formation and infection by ICAM-1-bearing
      virions. To further substantiate these results, we made use of mutant cell lines
      expressing LFA-1 in either a low (parental HPB-ALL and HAmut) or a high affinity
      state for ICAM-1 (HAP4) and compared syncytium formation and virus infection.
      Cells expressing the activated form of LFA-1 were found to be more susceptible to
      HIV-1-induced syncytium formation and to infection by ICAM-1-bearing HIV-1
      particles. The observed increase was solely due to the LFA-1 activation state
      because it was abrogated by anti-LFA-1 or anti-ICAM-1 antibodies and not due to
      variations in surface expression of LFA-1, CD4, or the chemokine coreceptor
      CXCR4. However, a linear relation was seen between the level of CXCR4 surface
      expression and susceptibility to syncytium formation/virus infection when ICAM-1
      LFA-1 interaction was either absent (i.e., infection with ICAM-1-negative
      virions) or abrogated (treatment with anti-LFA-1 or anti-ICAM-1 antibodies).
      These results emphasize the important role of the LFA-1 activation state with
      respect to virus-induced syncytium formation and HIV-1 infection.

PMID- 10208937
TI  - Differentiation-induced changes in promoter usage for transcripts encoding the
      human papillomavirus type 31 replication protein E1.
AB  - The life cycle of human papillomaviruses (HPVs) is tied to keratinocyte
      differentiation. One key event in the viral life cycle is the differentiation
      dependent increase in viral replication. This increase in replication activity
      results in an amplification of the HPV genome from approximately 50 copies per
      cell in basal keratinocytes to thousands of copies of the viral genome per cell
      in suprabasal keratinocytes. To characterize the events associated with this
      differentiation-dependent increase in HPV replication, we have initiated studies
      of mRNAs encoding the HPV replication protein E1 during the differentiation of
      cell lines that stably maintain episomal HPV DNA. Differentiation induced the
      expression of several transcripts that hybridized to an E1-specific probe. One of
      these messages, a 3.7-kb transcript, did not hybridize to a probe specific for
      the early promoter upstream of the E6 open reading frame. RNase protection
      analysis confirmed an induction of unspliced messages derived from the
      differentiation-dependent promoter at nucleotide 742 in the middle of the E7 open
      reading frame. These observations demonstrate a differentiation-induced increase
      in E1 mRNAs derived from the viral late promoter and suggest a role for increased
      E1 expression during amplification of the HPV genome.

PMID- 10208938
TI  - In vitro assembly properties of wild-type and cyclophilin-binding defective human
      immunodeficiency virus capsid proteins in the presence and absence of cyclophilin
      A.
AB  - The cellular protein cyclophilin A (CypA) binds specifically to the human
      immunodeficiency virus type 1 (HIV-1) capsid (CA) protein and is incorporated
      into HIV-1 particles at a molar ratio of 1:10 (CypA/CA). Structural analysis of a
      CA-CypA complex suggested that CypA may destabilize interactions in the viral
      capsid and thus promote uncoating. We analyzed the influence of CypA on the in
      vitro assembly properties of wild-type (WT) CA and derivatives containing
      substitutions of Gly89 in the Cyp-binding loop. All variant proteins were
      significantly impaired in CypA binding. In the presence of CypA at a molar ratio
      of 1:10 (CypA/CA), WT CA assembled into hollow cylinders that were similar to
      those observed in the absence of CypA but slightly longer. Higher CypA
      concentrations inhibited cylinder formation. Variant CA proteins G89L and G89F
      yielded similar cylinders as the WT protein but were significantly more resistant
      to CypA. Cryoelectron microscopic analysis of WT cylinders assembled in the
      presence of CypA revealed direct binding of CypA to the outer surface. Electron
      diffraction patterns generated from these cylinders indicated that CypA causes
      local disorder. The addition of CypA to preassembled cylinders had little effect,
      however, and cylinders were only disrupted when incubated with a threefold molar
      excess of CypA for several hours. These results suggest that CypA does not
      efficiently destabilize CA interactions at the molar ratio observed in the virion
      and therefore is unlikely to serve as an uncoating factor.

PMID- 10208939
TI  - Cyclophilin A incorporation is not required for human immunodeficiency virus type
      1 particle maturation and does not destabilize the mature capsid.
AB  - The cellular protein cyclophilin A (CypA) is packaged into human immunodeficiency
      virus type 1 (HIV-1) virions through a specific interaction with the capsid (CA)
      domain of the Gag polyprotein. CypA is important for infectivity, but its role in
      viral replication is currently unknown. Previous reports suggested that CypA
      promotes uncoating or enhances maturation. We analyzed the morphology and capsid
      stability of HIV-1 variants defective in CypA binding and of virus grown in the
      presence of cyclosporin. Both cyclosporin treatment and alteration of Gly89 or
      Pro90 in the CypA-binding site of CA caused a 5- to 20-fold decrease in CypA
      incorporation. Virus produced from cyclosporin-treated cells and variants G89V
      and G89A were 10- to 100-fold less infectious but exhibited normal virion
      morphologies with regular cone-shaped capsids. Irregular capsid morphologies and
      lower infectivities were observed for some other variants in the CypA-binding
      region. Decreased CypA incorporation did not reduce the kinetics of intracellular
      polyprotein processing or of virus release. No increase in immature particles was
      observed. These results suggest that CypA does not promote virion maturation.
      Furthermore, detergent stripping of virus particles with various CypA contents
      revealed no difference in capsid stability. Based on these results and those
      reported in the accompanying paper, it appears likely that CypA also is not an
      uncoating factor. Alternative models for CypA function are discussed.

PMID- 10208940
TI  - Prospects for preventing asthma.

PMID- 10208941
TI  - Glutaric aciduria and suspected child abuse.

PMID- 10208942
TI  - Delphi study into planning for care of children in major incidents.
AB  - This paper describes a Delphi study used to identify and improve areas of concern
      in the planning of care for children in major incidents. The Delphi was conducted
      over three rounds and used a multidisciplinary panel of 22 experts. Experts were
      selected to include major incident, immediate care, emergency medicine, and
      paediatric specialists. This paper presents a series of consensus statements that
      represent the Delphi group's opinion on the management of children in major
      incidents. The statements cover all phases of major incident planning and
      response. Paediatric services may play a vital role in the preparation and
      response to a major incident involving children. This paper represents a
      consensus view on how best to plan and respond to major incidents involving
      children. An accompanying paper describes the practical implementation of this
      guidance.

PMID- 10208943
TI  - Planning for major incidents involving children by implementing a Delphi study.
AB  - This paper provides a practical approach to the difficult problem of planning for
      a major incident involving children. It offers guidance on how general principles
      resulting from an expert Delphi study can be implemented regionally and locally.
      All phases of the response are covered including preparation, management of the
      incident, delivery of medical support during the incident, and recovery and
      support. A check list for regional planners is provided. Supplementary equipment
      is discussed and action cards for key roles in the paediatric hospital response
      are shown. Particular emphasis is placed on management of the secondary-tertiary
      interface including the special roles of paediatric assessment teams and
      paediatric transfer teams. A paediatric primary triage algorithm is provided. The
      important role of local interpretation of guidance is emphasised.

PMID- 10208944
TI  - Validation of an asthma symptom diary for interventional studies.
AB  - OBJECTIVE: The Pediatric Asthma Diary was developed and validated to assess
      efficacy of interventions in children with asthma. DESIGN, PATIENTS, AND SETTING:
      Diary validation was performed in a three week, prospective study of 106 children
      aged 6-14 years with asthma. Children were classified at baseline as either
      stable (requiring no additional asthma treatment) or new onset/worse (requiring
      either addition of or increase in anti-inflammatory treatment). RESULTS: A
      daytime symptom scale and "day without asthma" were defined from diary questions.
      Both measures demonstrated significant validity and responsiveness to anti
      inflammatory treatment. The stable group experienced a higher percentage of days
      without asthma during week 1 compared with the new onset/worse group (39.6% v
      11.6%, respectively). The new onset/worse patients experienced significant
      improvement in days without asthma (24.5%) compared with stable patients (6.4%).
      CONCLUSIONS: The Pediatric Asthma Diary daytime symptom scale and day without
      asthma are acceptable measures for use in asthma intervention studies of children
      aged 6-14 years.

PMID- 10208945
TI  - A randomised controlled trial to assess the relative benefits of large volume
      spacers and nebulisers to treat acute asthma in hospital.
AB  - OBJECTIVES: To compare the clinical effectiveness, acceptability, and cost
      benefit of administering beta2 agonists by means of a metered dose inhaler and
      large volume spacer with conventional nebulisers to children admitted to hospital
      with acute asthma. METHODS: A randomised controlled trial was conducted over five
      months. Sixty one children older than 3 years admitted to a large teaching
      hospital and a district general hospital with acute asthma completed the study.
      Children received either 5 mg of salbutamol up to one hourly by jet nebuliser, or
      up to 10 puffs of salbutamol 100 microg by means of a metered dose inhaler and
      spacer up to one hourly. RESULTS: Median hospital stay was 40 hours in the
      nebuliser group and 36.5 hours in the spacer group. Asthma disability scores at
      two weeks after discharge were significantly improved in the spacer group. Drug
      costs were pound 14.62 less for each patient in the spacer group. CONCLUSIONS:
      Large volume spacers are an acceptable, cost effective alternative to nebulisers
      in treating children admitted with acute asthma, provided that the children can
      use the mouthpiece, and symptoms are not severe. Their use facilitates effective
      home treatment by parents, with subsequent reduction in morbidity and re
      admission rates.

PMID- 10208946
TI  - Withdrawal and limitation of life support in paediatric intensive care.
AB  - OBJECTIVES: To compare the modes of death and factors leading to withdrawal or
      limitation of life support in a paediatric intensive care unit (PICU) in a
      developing country. METHODS: Retrospective analysis of all children (< 12 years)
      dying in the PICU from January 1995 to December 1995 and January 1997 to June
      1998 (n = 148). RESULTS: The main mode of death was by limitation of treatment in
      68 of 148 patients, failure of active treatment including cardiopulmonary
      resuscitation in 61, brain death in 12, and withdrawal of life support with
      removal of endotracheal tube in seven. There was no significant variation in the
      proportion of limitation of treatment, failure of active treatment, and brain
      death between the two periods; however, there was an increase in withdrawal of
      life support from 0% in 1995 to 8% in 1997-98. Justification for limitation was
      based predominantly on expectation of imminent death (71 of 75). Ethnic
      variability was noted among the 14 of 21 patients who refused withdrawal.
      Discussions for care restrictions were initiated almost exclusively by
      paediatricians (70 of 75). Diagnostic uncertainty (36% v 4.6%) and presentation
      as an acute illness were associated with the use of active treatment.
      CONCLUSIONS: Limitation of treatment is the most common mode of death in a
      developing country's PICU and active withdrawal is still not widely practised.
      Paediatricians in developing countries are becoming more proactive in managing
      death and dying but have to consider sociocultural and religious factors when
      making such decisions.

PMID- 10208947
TI  - GB virus C/hepatitis G virus infection in HIV infected patients with haemophilia
      despite treatment with virus inactivated clotting factor concentrates.
AB  - AIM: To determine the frequency of GB virus C (GBV-C)/hepatitis G virus (HGV)
      infection before and after switch to the use of virus inactivated concentrates in
      haemophiliac patients infected with human immunodeficiency virus (HIV). PATIENTS
      AND METHODS: Initial and follow up sera from 49 children with haemophilia were
      analysed for the presence of GBV-C/HGV RNA and antibodies to HGV (anti-HGV). All
      patients had been infected with HIV while receiving concentrates without virus
      inactivation before 1984 and were subsequently treated with virus inactivated
      concentrates. RESULTS: In the first available serum sample (1987 or later), two
      of 49 patients were GBV-C/HGV RNA positive and two further patients were anti-HGV
      positive. During follow up (mean, 6 years), 14 patients developed markers of GBV
      C/HGV infection. Eleven of these had received no blood products except clotting
      factor concentrates that had been prepared with virus inactivation. CONCLUSIONS:
      Despite being treated with virus inactivated clotting factor concentrates, HIV
      positive patients with haemophilia are at an increased risk of manifesting GBV
      C/HGV infection. We hypothesise that GBV-C/HGV is transmitted by these clotting
      factor concentrates. However, we cannot rule out the emergence of markers of GBV
      C/HGV infection as a result of the progression of immune impairment in the course
      of HIV infection.

PMID- 10208948
TI  - Childhood tuberculosis in an urban population in South Africa: burden and risk
      factor.
AB  - AIM: To study the epidemiology of childhood tuberculosis (TB) in a developing
      country. SETTING: Two urban communities of Cape Town, South Africa with a TB case
      notification rate of 1149/100 000. DESIGN: Retrospective descriptive study using
      the national population census (1991), 10 year official TB notification records,
      and a geographical information system. RESULTS: The case notification rate of TB
      in children 0-5 years old was 3588 cases/100 000 children aged 0-5 years, 3.5
      times the case notification rate in adults. Children (0-14 years) accounted for
      39% of the total case load. Childhood TB case notification rate correlated with
      parental education (r = -0.64), annual household income (r = -0.6), and crowding
      (r = 0.32). CONCLUSION: Children, especially those living in poor socioeconomic
      conditions, form an important epidemiological group and account for a notable
      proportion of the morbidity caused by TB. Efforts to improve TB control must
      therefore not only target adults (case detection and cure of infectious cases)
      but also children (screening of child contacts of adult cases) and the
      socioeconomic living conditions.

PMID- 10208949
TI  - Insulin-like growth factor I response during nutritional rehabilitation of
      persistent diarrhoea.
AB  - OBJECTIVE: Evaluation of nutritional recovery, intestinal permeability, and
      insulin-like growth factor I (IGF-I) response in malnourished children with
      persistent diarrhoea and their relation to concomitant systemic infection(s).
      STUDY DESIGN: Open study of severely malnourished children (aged 6-36 months)
      with persistent diarrhoea (>/= 14 days) admitted for nutritional rehabilitation
      with a standardised rice-lentil and yogurt diet. Successful recovery was defined
      prospectively as overall weight gain (> 5 g/kg/day) with a reduction in stool
      output by day 7 of treatment. Data on coexisting infections and serum C reactive
      protein (CRP) were collected at admission. RESULTS: Of 63 children, 48 (group A)
      recovered within seven days of dietary treatment. These children had a
      significant increase in serum IGF-I (DeltaIGF-I%) and, in contrast to serum
      prealbumin and retinol binding protein, DeltaIGF-I% correlated with weight gain
      (r = 0.41). There was no correlation between the IGF-I response and intestinal
      permeability as assessed by urinary lactulose/rhamnose excretion. Treatment
      failures (group B) included more children with clinical (relative risk, 4.8; 95%
      confidence interval, 1.2 to 19.7) and culture proven sepsis at admission and
      higher concentrations of serum CRP (median (range), 36 (0-182) v 10 (0-240) mg/l)
      at admission. There was a negative correlation between admission CRP
      concentration and DeltaIGF-I% (r = -0.45). CONCLUSIONS: In comparison with serum
      albumin, prealbumin, and retinol binding protein, serum IGF-I increment is a
      better marker of nutritional recovery in malnourished children with persistent
      diarrhoea. The possible association of systemic infections, serum IGF-I response,
      and mucosal recovery needs evaluation in future studies.

PMID- 10208951
TI  - Plasma vasopressin and response to treatment in primary nocturnal enuresis.
AB  - AIMS: To examine the relation between nocturnal vasopressin release and response
      to treatment with the vasopressin analogue 1-desamino-8-D-arginine vasopressin
      (DDAVP) in children with primary monosymptomatic nocturnal enuresis. DESIGN:
      Children were recruited from a specific enuresis clinic and entered into a
      defined treatment programme. Nocturnal vasopressin concentrations were measured
      every 15 minutes over a four hour period during overnight admission. RESULTS:
      Sixty seven children were eligible for entry into the study, 35 of whom agreed to
      overnight sampling. There was a quadratic relation between mean plasma AVP and
      response to treatment with DDAVP, with very high or very low concentrations being
      unresponsive. Plasma AVP profiles ranged from low concentrations with little
      variability to high concentrations with wide variability. CONCLUSION: The ability
      to respond to DDAVP is related to endogenous AVP production and is influenced by
      neuronal patterning in early infancy. The best predictors of success with
      treatment were a past history of breast feeding, mean nocturnal AVP
      concentration, and the height of the child. The response was adversely affected
      by poor weight at birth and poor linear growth. The study suggests differing
      causes of nocturnal enuresis related to different patterns of AVP release.

PMID- 10208950
TI  - Failure of IGF-I and IGFBP-3 to diagnose growth hormone insufficiency.
AB  - BACKGROUND: Growth hormone insufficiency (GHI) is diagnosed conventionally by
      short stature and slow growth, and is confirmed by diminished peak GH response to
      a provocation test. Insulin-like growth factor I (IGF-I) and IGF binding protein
      3 (IGFBP-3) have previously been considered individually OBJECTIVE: To test the
      hypothesis that the combined analysis of IGF-I and IGFBP-3 could act as a
      surrogate marker for the diagnosis of GHI. DESIGN: Reference ranges for IGF-I and
      IGFBP-3 were calculated using 521 normal individuals. A retrospective analysis
      was performed on 318 children referred for investigation of short stature.
      RESULTS: No significant difference was found between either the IGF-I or IGFBP-3
      standard deviation scores (SDSs) in children with and without GHI. If the
      requirement were for both tests to be positive (< -2 SDS) for a diagnosis of GHI,
      then 99% of children without GHI would be correctly identified; however, the
      sensitivity of the test was only 15%. CONCLUSIONS: Neither IGF-I nor IGFBP-3
      alone is a marker for GHI. In addition, they cannot be used as an effective
      screening test in combination.

PMID- 10208952
TI  - Ovarian function after bone marrow transplantation performed before menarche.
AB  - AIM: To examine the long term effect of bone marrow transplantation (BMT) on
      ovarian function in girls. METHODS: Eighteen girls who underwent BMT before
      menarche, had been disease free for more than six years, and were over 14 years
      of age at the time of study were investigated. The preparative regimen consisted
      of irradiation and chemotherapy. The occurrence of menarche and changes in basal
      serum follicle stimulating hormone (FSH) concentrations were studied. RESULTS:
      Twelve patients achieved menarche at a median age of 12.8 years. Age at
      transplant was significantly younger in patients who achieved menarche than in
      those who did not (mean (SD), 7.2 (0.5) v 11.1 (1.7) years). Basal FSH began to
      rise to menopausal concentrations after 10 years of age, and the girls who did
      not experience menarche had a sustained rise in FSH concentrations. Among those
      with raised FSH concentrations, five girls experienced menarche while serum FSH
      values were decreasing and four achieved menarche while FSH remained raised.
      CONCLUSIONS: The high incidence of menarche suggests a favourable outcome of
      ovarian function in girls who undergo BMT at a young age.

PMID- 10208953
TI  - Unscheduled return visits within 72 hours to an assessment unit.
AB  - Unscheduled return visits were looked at to determine the quality of care and
      safety of patients in a paediatric assessment unit. The reasons for unscheduled
      return visits were also investigated. Two per cent of patients discharged from
      the unit returned, the main reason being parental perception of illness. There
      were only two patients re-referred by their family doctor. These findings have
      implications for clinical care and education.

PMID- 10208954
TI  - Outcome of medium chain acyl-CoA dehydrogenase deficiency after diagnosis.
AB  - BACKGROUND: Medium chain acyl-CoA dehydrogenase (MCAD) deficiency is the most
      common inborn error of fatty acid metabolism. Undiagnosed, it has a mortality
      rate of 20-25%. Neonatal screening for the disorder is now possible but it is not
      known whether this would alter the prognosis. OBJECTIVE: To investigate the
      outcome of MCAD deficiency after the diagnosis has been established. METHOD: All
      patients with a proved diagnosis of MCAD deficiency attending one centre in a
      four year period were reviewed. RESULTS: Forty one patients were identified.
      Follow up was for a median of 6.7 years (range, 9 months to 14 years). Nearly
      half of the patients were admitted to hospital with symptoms characteristic of
      MCAD deficiency before the correct diagnosis was made. After diagnosis, two
      patients were admitted to hospital with severe encephalopathy but there were no
      additional deaths or appreciable morbidity. There was a high incidence (about one
      fifth) of previous sibling deaths among the cohort. CONCLUSIONS: Undiagnosed,
      MCAD deficiency results in considerable mortality and morbidity. However, current
      management improves outcome, supporting the view that the disorder should be
      included in newborn screening programmes.

PMID- 10208955
TI  - An inborn error of bile acid synthesis (3beta-hydroxy-delta5-C27-steroid
      dehydrogenase deficiency) presenting as malabsorption leading to rickets.
AB  - Deficiency of 3beta-hydroxy-delta5-C27-steroid dehydrogenase (3beta-HSDH), the
      enzyme that catalyses the second reaction in the principal pathway for the
      synthesis of bile acids, has been reported to present with prolonged neonatal
      jaundice with the biopsy features of neonatal hepatitis. It has also been shown
      to present between the ages of 4 and 46 months with jaundice, hepatosplenomegaly,
      and steatorrhoea (a clinical picture resembling progressive familial intrahepatic
      cholestasis). This paper reports two children with 3beta-HSDH deficiency who
      developed rickets during infancy and did not develop clinically evident liver
      disease until the age of 3 years. Bile acid replacement resulted in considerable
      clinical and biochemical improvement. The importance of thorough investigation of
      fat soluble vitamin deficiencies in infancy is emphasised.

PMID- 10208956
TI  - Improved prognosis for congenital nephrotic syndrome of the Finnish type in Irish
      families.
AB  - Congenital nephrotic syndrome of the Finnish type is a rare autosomal recessive
      disease with a high infant mortality without aggressive treatment. The
      biochemical basis of the disease is not understood fully but the disease locus
      has been mapped recently to chromosome 19q12-q13.1 in Finnish families. This
      paper describes the clinical features and outcome of 20 patients in Ireland with
      congenital nephrotic syndrome of the Finnish type who have presented since 1980.
      Before 1987, all infants died by the age of 3 years. After the introduction of
      daily intravenous albumin infusion, nutritional support, elective bilateral
      nephrectomy, and renal transplantation, mortality in the past decade has fallen
      to 30%, with no deaths in the past five years. Genetic linkage analysis was
      performed in six families in whom DNA was available and the locus responsible was
      mapped to the same region on chromosome 19 as in Finnish families, suggesting
      that Irish families share the same disease locus.

PMID- 10208957
TI  - Prolonged QT interval in Rett syndrome.
AB  - Rett syndrome is a severe neurodevelopmental disorder of unknown aetiology. A
      prolonged QT interval has been described previously in patients with Rett
      syndrome. To investigate QT prolongation and the presence of cardiac
      tachyarrhythmias in Rett syndrome electrocardiography and 24 hour Holter
      monitoring were performed prospectively in a cohort of 34 girls with Rett
      syndrome. The corrected QT value was prolonged in nine patients. Compared with a
      group of healthy controls of a similar age range, the patients with Rett syndrome
      had significantly longer corrected QT values. Clinical severity was not a
      predictor for prolonged QT intervals in the Rett syndrome cohort. The prolonged
      QT syndrome is a serious and potentially lethal cardiac disorder and should be
      considered in all girls with Rett syndrome.

PMID- 10208958
TI  - Hereditary pancreatitis and mutation of the trypsinogen gene.
AB  - Hereditary pancreatitis is a rare form of chronic recurrent pancreatitis. A
      family, in which 11 members had chronic pancreatitis, five had diabetes, and two
      had pancreatic cancer, was studied, and hereditary pancreatitis was diagnosed in
      all patients by demonstrating the mutation in exon 3 of the cationic trypsinogen
      gene (R117H). The clinical implications of genotypic analysis in hereditary
      pancreatitis are discussed.

PMID- 10208959
TI  - Cardiovascular effects of mechanical ventilation.

PMID- 10208960
TI  - Learning in preschool children with neurological disability.

PMID- 10208961
TI  - The effect of Calman reforms on recruitment training and service provision.

PMID- 10208963
TI  - Injury in the young 

PMID- 10208964
TI  - Young carers and their families 

PMID- 10208962
TI  - A regionalised transport service, the way ahead?

PMID- 10208965
TI  - Expression and localization of messenger ribonucleic acid for the vitellogenin
      receptor in ovarian follicles throughout oogenesis in the rainbow trout,
      Oncorhynchus mykiss.
AB  - The expression and localization of vitellogenin (VTG) receptor (VTGR) mRNA were
      identified throughout ovarian development in the rainbow trout, Oncorhynchus
      mykiss. Northern blot confirmed the presence of a transcript (approximately 3.9
      kilobases [kb]) that was specific to the ovary. The expression of VTGR mRNA
      varied throughout ovarian development and was highest in previtellogenic ovaries
      and in ovaries at the onset of vitellogenesis containing ovarian follicles (OF)
      from 35 to 600 microm in diameter. In situ hybridization using 35S riboprobes
      showed that the transcription of the VTGR gene was initiated in OF measuring 45
      50 microm in diameter, with transcripts being exclusively localized in the
      ooplasm. A dramatic increase in mRNA synthesis occurred during previtellogenic
      growth (OF from 50 to 200 microm); this was followed by a gradual decrease during
      the vitellogenic growth phase. VTGR mRNA was not detected in OF greater than 1000
      microm in diameter (oocytes actively sequestering VTG). Immunocytolocalization of
      yolk proteins derived from VTG demonstrated that oocytes started to sequester VTG
      when they were around 300 microm in diameter, shortly after the time of maximal
      density of VTGR mRNA in the ooplasm. The timing of transcription of the VTGR
      gene, predominantly during previtellogenesis, suggests that the VTGR is recycled
      to the oocyte surface during the vitellogenic growth phase.

PMID- 10208967
TI  - Expression of granulosa cell-specific genes and induction of apoptosis in
      conditionally immortalized granulosa cell lines established from H-2Kb-tsA58
      transgenic mice.
AB  - Granulosa cell lines have been established from H-2Kb-tsA58 transgenic mice.
      Using immunocytochemistry, significant amounts of insulin-like growth factor-I
      (IGF-I) were found in all cell lines investigated, whereas estrogen and
      progesterone receptor expression could be detected in only some of the lines. All
      cell lines showed low basal production of the gonadal steroids estradiol and
      progesterone. The genes for the ovarian paracrine regulators IGF-I and basic
      fibroblast growth factor were expressed, as well as the genes for anti-Mullerian
      hormone and for the P450 side-chain cleavage enzyme (P450scc). Expression of
      P450scc could be shown to be up-regulated in the cell lines under conditions
      mimicking the hormonal environment of the luteinizing granulosa cells in vivo.
      Inactivation of the temperature-sensitive SV40 T antigen by a shift of the cell
      lines to the nonpermissive temperature of 39.5 degrees C led to massive induction
      of apoptosis in several cell lines. These cell lines will allow a detailed study
      of the mechanisms regulating the expression of granulosa cell-specific functions,
      as well as the induction of granulosa cell apoptosis.

PMID- 10208966
TI  - Identification of a new aspartic proteinase expressed by the outer chorionic cell
      layer of the equine placenta.
AB  - The pregnancy-associated glycoproteins (PAGs) are placental antigens that were
      initially characterized as pregnancy markers in the maternal circulation of
      domestic ruminant species. They are members of the aspartic proteinase gene
      family, having greatest sequence identity with pepsinogens. However, some are not
      capable of functioning as enzymes. The PAGs are associated with a large gene
      family within the Artiodactyla order (cattle, camels, pigs). So far, no members
      of this family have been characterized in species outside this order. This report
      describes the cloning and initial characterization of a PAG-like protein (equine
      PAG or ePAG) expressed in the placenta of the horse and zebra (order
      Perrisodactyla). Equine PAG is a proteinase capable of degrading 14C-hemoglobin
      and catalyzing the removal of its own pro-peptide. The ePAG mRNA is restricted to
      the chorion both prior to implantation and in the term placenta. Equine PAG is
      secreted from cultured placental tissue as both a processed (mature) and
      unprocessed (zymogen) form. Equine PAG shares similar identity with the PAGs and
      pepsinogens and probably arose from a pepsinogen-like precursor that gained the
      ability to be expressed in the placenta. The promoter of the ePAG gene shares
      sequence identity with the promoter from a bovine PAG gene but not with promoters
      of other aspartic proteinases. Therefore, we hypothesize that ePAG is a remnant
      of the pepsinogen-like progenitor gene that was expanded within the Artiodactyla
      to create the large and highly diverse PAG family.

PMID- 10208968
TI  - Accumulation of caspase-3 messenger ribonucleic acid and induction of caspase
      activity in the ovine corpus luteum following prostaglandin F2alpha treatment in
      vivo.
AB  - Caspase-3, a vertebrate homologue of the protein encoded by the Caenorhabditis
      elegans cell death gene, ced-3, induces apoptosis when overexpressed in
      eukaryotic cells. Since apoptosis occurs during corpus luteum (CL) regression in
      many species, including the ewe, these studies were conducted to 1) isolate a
      cDNA encoding ovine caspase-3, 2) measure steady state amounts of caspase-3 mRNA
      in the CL during luteolysis induced by prostaglandin F2alpha (PGF2alpha) and
      during the time of maternal recognition of pregnancy, and 3) measure changes in
      caspase activity during PGF2alpha-initiated luteal regression. Oligonucleotide
      primers corresponding to a human caspase-3 cDNA sequence were combined with total
      RNA from ovine CL in a reverse transcription-polymerase chain reaction-based
      procedure to amplify a 640-base pair partial cDNA with a nucleotide sequence 86%
      and 81% identical to the human and rat caspase-3 cDNAs, respectively. CL were
      collected from ewes at 0, 12, or 24 h after treatment with PGF2alpha on Day 10 of
      the estrous cycle and from nonpregnant and pregnant ewes on Day 12 or Day 14 of
      the cycle. Northern blot analysis of total cellular RNA from ovine CL and a
      radiolabeled ovine caspase-3 cRNA probe indicated the presence of a single mRNA
      transcript of approximately 2.5 kilobases. Levels of caspase-3 mRNA were
      approximately 3-fold higher (p < 0.05) in CL at 12 h and 24 h after PGF2alpha in
      comparison to those levels measured in matched CL from untreated ewes. There were
      no differences (p > 0.05) in amounts of caspase-3 mRNA in CL on Day 12 or Day 14
      of the estrous cycle compared to Day 12 or Day 14 of pregnancy, respectively.
      Caspase activity in CL (measured by the ability of CL lysates to cleave an
      artificial caspase substrate) was also significantly (p < 0.05) increased in CL
      collected after treatment with PGF2alpha compared to CL collected from nontreated
      ewes. We conclude that physiological cell death during PGF2alpha-induced luteal
      regression in the ewe is mediated, at least in part, via increased expression and
      activity of the caspase family of pro-apoptotic proteases.

PMID- 10208969
TI  - Molecular cloning, genetic mapping, and developmental expression of bovine
      POU5F1.
AB  - We describe isolation and characterization of the bovine ortholog of POU5F1
      (bPOU5F1) encoding octamer-binding transcription factor-4 (Oct-4). The
      organization of bPOU5F1 is similar to its human and murine orthologs, and it
      shares 90.6% and 81.7% overall identity at the protein level, respectively.
      Transient transfection of luciferase reporter constructs in murine P19 embryonal
      carcinoma cells demonstrated that bPOU5F1 has a functional promoter and contains
      two enhancer elements, of which one is repressed by retinoic acid. bPOU5F1 was
      mapped to the major histocompatibility complex on chromosome 23. bPOU5F1 mRNA was
      detected by nested reverse transcription-polymerase chain reaction in immature
      oocytes and in in vitro-produced preattachment-stage embryos. Oct-4 in oocytes
      and in vitro-produced preattachment-stage embryos was demonstrated by indirect
      immunofluorescence. Confocal laser scanning microscopy revealed Oct-4 in both the
      inner cell mass and trophoblast cells of the blastocyst until Day 10 of
      development. Immunofluorescence performed on the outgrowths formed at Day 13
      postfertilization from in vitro-produced Day 8 blastocysts showed Oct-4 staining
      in all cells. This expression pattern suggests that bPOU5F1 acts early in bovine
      embryonic development but that its expression is not restricted to pluripotent
      cells of the blastocyst.

PMID- 10208970
TI  - Angiotensin II interacts with prostaglandin F2alpha and endothelin-1 as a local
      luteolytic factor in the bovine corpus luteum in vitro.
AB  - Recent findings suggest that the ovarian renin-angiotensin system may regulate
      ovarian function through the paracrine/autocrine actions of angiotensin II (Ang
      II). In this study, we have examined and characterized the local effects of Ang
      II as a luteolytic factor and its interaction with prostaglandin F2alpha
      (PGF2alpha) and endothelin-1 (ET-1) in the bovine corpus luteum (CL) of the mid
      luteal phase, by using an in vitro microdialysis system (MDS). Ang II was
      detected in the MDS perfusate (4 pg/ml), and infusion of PGF2alpha (10(-6) M) for
      2 h increased the Ang II release by 50-100% during the following experimental
      period, in addition to its stimulation of ET-1 release. Two 2-h infusions of Ang
      II (10(-7)-10(-5) M) separated by a 2-h interval induced a dose- and time
      dependent decrease of progesterone (P4) release by 41-66%. When the luteal
      explants were pre-perfused with PGF2alpha (10(-6) M) for 2 h, two consecutive
      perfusions of Ang II (10(-6) M) at a 2-h interval rapidly reduced the P4 release
      (by 50%). This reduction occurred 6 h earlier than those of infusions of
      PGF2alpha or Ang II alone. The simultaneous infusion of either 1) Ang II (10(-6)
      M) with PGF2alpha (10(-6) M), 2) ET-1 (10(-7) M) with PGF2alpha, or 3) Ang II +
      ET-1 with PGF2alpha (10(-6) M) for 2 h also induced a rapid and pronounced (60%)
      decrease in P4 release. Perfusion with the Ang II antagonist blocked the P4
      suppressing activity of Ang II alone or PGF2alpha + Ang II infusion. Ang II
      stimulated the release of ET-1 and oxytocin during infusion but inhibited them
      after infusion. These results show that Ang II is released in the bovine midcycle
      CL in vitro, and this peptide, either alone or together with PGF2alpha, can
      suppress the release of P4. As PGF2alpha directly stimulated Ang II release, Ang
      II may influence the critical period for starting the cascade of functional
      luteolysis in vivo and might lead to structural luteolysis with ET-1 as a major
      vasoconstrictor. The overall results suggest that Ang II may have an important
      role at luteolysis in the bovine CL.

PMID- 10208971
TI  - Growth retardation of inner cell mass cells in polyspermic porcine embryos
      produced in vitro.
AB  - The in vitro viability of polyspermic pig eggs was investigated. Immature oocytes
      were matured and fertilized in vitro. Approximately 10 h after insemination, the
      eggs were centrifuged at 12 000 x g for 10 min and individually classified into
      two (2PN)- and poly-pronuclear (PPN, 3 or 4 pronuclei) eggs. The classified eggs
      were cultured in vitro or in vivo. Nuclei numbers of inner cell mass (ICM) and
      trophectoderm (TE) were compared between 2PN- and PPN-derived blastocysts. The
      frequency of development in vitro of 2PN and PPN eggs to the blastocyst stage was
      53.6% and 40.7%, respectively. The mean number (8.2 +/- 0.7, n = 48) of ICM
      nuclei of 2PN-derived blastocysts was higher than that (4.2 +/- 0.8, n = 37) of
      PPN-derived blastocysts (p < 0.001), whereas there was no difference (p > 0.05)
      in mean numbers of total (46.7 +/- 3.4 vs. 39. 9 +/- 3.9) and TE nuclei (38.5 +/-
      2.9 vs. 35.7 +/- 3.3) between the two groups. Development of 2PN and PPN eggs
      cultured in vivo to the blastocyst stage was 33.3% and 27.4%, respectively. The
      numbers of ICM and TE nuclei of these embryos cultured in vivo showed a pattern
      similar to that for the in vitro-produced blastocysts. Additionally, fetuses were
      obtained on Day 21 from both the 2PN and the PPN groups. This suggests that
      polyspermic pig embryos develop to the blastocyst stage and beyond, although
      showing a smaller ICM cell number as compared to normal embryos.

PMID- 10208972
TI  - Identification of two major histocompatibility complex class Ib genes, Q7 and Q9,
      as the Ped gene in the mouse.
AB  - The Ped (preimplantation embryonic development) gene influences the rate of
      preimplantation embryonic development and subsequent embryonic survival. The
      protein product of the Ped gene, the Qa-2 protein, is a major histocompatibility
      complex (MHC) class Ib protein. There are two alleles of the Ped gene, fast (Qa-2
      [+]) and slow (Qa-2 [-]). Qa-2 is encoded by four very similar MHC class Ib
      genes: Q6, Q7, Q8, and Q9. Recent research in our laboratory has shown that the
      Ped phenotype is potentially encoded by the Q7 and/or Q9 gene because the Q7 and
      Q9 genes, but not the Q6 or Q8 gene, are expressed during preimplantation mouse
      embryonic development. In this study we utilized microinjection of transgenes to
      assess the functional roles of both the Q7 and Q9 genes in control of the rate of
      preimplantation development. The Q7 gene, the Q9 gene, and a combination of the
      Q7 and Q9 genes were microinjected into Ped slow zygotes, and the Ped phenotype
      and cell surface expression of Qa-2 protein were assayed after a 72-h or 96-h
      incubation period. We found that the microinjected individual Q7 and Q9 genes
      increased the rate of preimplantation development. Simultaneous injection of the
      Q7 and Q9 genes did not have a synergistic effect on the Ped phenotype.
      Microinjection of the Q7 and/or Q9 genes resulted in protein expression in 10-25%
      of the microinjected embryos. These results show that both the Q7 and Q9 genes
      encode the mouse Ped phenotype.

PMID- 10208973
TI  - Intrafollicular content of luteinizing hormone receptor, alpha-inhibin, and
      aromatase in relation to follicular growth, estrous cycle stage, and oocyte
      competence for in vitro maturation in the mare.
AB  - The intrafollicular content of LH receptor, alpha-inhibin, and aromatase are
      known good indicators of follicular status. We investigated the amounts of these
      proteins in granulosa and cumulus cells in relation to oocyte competence for in
      vitro maturation, follicular growth, and estrous cycle stage in the mare.
      Follicular punctures were performed 34 h after an injection of crude equine
      gonadotropins, either during the follicular phase, at the end of the follicular
      phase, or during the luteal phase. The cumulus-oocyte complex, granulosa cells,
      and follicular fluid of follicles larger than 5 mm were collected. The nuclear
      stage of the oocytes after in vitro culture was determined microscopically.
      Granulosa and cumulus cell amounts of LH receptor, alpha-inhibin, and aromatase
      were assessed by the semiquantitative Western blot method and image analysis.
      Follicular fluids were assayed for progesterone (P4) and estradiol-17beta (E2).
      The three factors were expressed in mural granulosa and cumulus cells from all
      follicles from the gonadotropin-independent growth period until the preovulatory
      stage. Considering all the follicles punctured, the amounts of LH receptor and
      alpha-inhibin in granulosa cells were not different for the three physiological
      stages studied. The amounts of aromatase in granulosa cells, as well as the E2:P4
      ratios, were higher for follicles punctured during the follicular phase than for
      the two other groups (p < 0.05). Considering the data from the three groups, the
      E2:P4 ratio and the LH receptor and aromatase contents, but not alpha-inhibin, in
      granulosa cells increased with an increase in follicular diameter (p < 0.01). The
      E2:P4 ratios and the amounts of LH receptor, alpha-inhibin, and aromatase in
      granulosa cells were lower in follicles 5-9 mm in diameter than in larger ones (p
      < 0.05). In cumulus cells, the amounts of the three factors were different
      neither between the three groups nor between the follicular diameters. Although
      we could not establish any obvious relationship to oocyte competence for in vitro
      maturation, the influence of the follicle diameter on the content of LH
      receptors, alpha-inhibin, and aromatase in granulosa cells was similar to the
      influence of follicle diameter on oocyte competence. Therefore, one can
      hypothesize that, in the mare, there is a link between the acquisition of oocyte
      competence and the expression of these factors in the follicular cells.

PMID- 10208974
TI  - Calcium-dependent actin filament-severing protein scinderin levels and
      localization in bovine testis, epididymis, and spermatozoa.
AB  - We assessed the levels and localization of the actin filament-severing protein
      scinderin, in fetal and adult bovine testes, and in spermatozoa during and
      following the epididymal transit. We performed immunoblots on seminiferous
      tubules and interstitial cells isolated by enzymatic digestion, and on bovine
      chromaffin cells, spermatozoa, aorta, and vena cava. Immunoperoxidase labeling
      was done on Bouin's perfusion-fixed testes and epididymis tissue sections, and on
      spermatozoa. In addition, immunofluorescence labeling was done on spermatozoa.
      Immunoblots showed one 80-kDa band in chromaffin cells, fetal and adult tubules,
      interstitial cells, spermatozoa, aorta, and vena cava. Scinderin levels were
      higher in fetal than in adult seminiferous tubules but showed no difference
      between fetal and adult interstitial cells. Scinderin levels were higher in
      epididymal than in ejaculated spermatozoa. Scinderin was detected in a region
      corresponding with the subacrosomal space in the round spermatids and with the
      acrosome in the elongated spermatids. In epididymal spermatozoa, scinderin was
      localized to the anterior acrosome and the equatorial segment, but in ejaculated
      spermatozoa, the protein appeared in the acrosome and the post-equatorial segment
      of the head. In Sertoli cells, scinderin was detected near the cell surface and
      within the cytoplasm, where it accumulated near the base in a stage-specific
      manner. In the epididymis, scinderin was localized next to the surface of the
      cells; in the tail, it collected near the base of the principal cells. In Sertoli
      cells and epididymal cells, scinderin may contribute to the regulation of tight
      junctional permeability and to the release of the elongated spermatids by
      controlling the state of perijunctional actin. In germ cells, scinderin may
      assist in the shaping of the developing acrosome and influence the fertility of
      the spermatozoa.

PMID- 10208975
TI  - Transmembrane regulation of intracellular calcium by a plasma membrane
      sodium/calcium exchanger in mouse ova.
AB  - Regulation of cytoplasmic free calcium concentration ([Ca2+)]i) is a key factor
      for maintenance of viability of cells, including oocytes. Indeed, during
      fertilization of an ovum, [Ca2+]i is known to undergo oscillations, but it is
      unknown how basal [Ca2+]i or calcium oscillations are regulated. In the present
      study we investigated the role of the plasma membrane in regulating [Ca2+]i of
      metaphase II-arrested mouse oocytes (ova). Ova were collected from B6C3F1 mice
      treated with eCG (10 IU) and hCG (5 IU), and intracellular calcium was determined
      by means of fura-2. Extracellular calcium flux across the zona pellucida was
      detected noninvasively by a calcium ion-selective, self-referencing
      microelectrode that was positioned by a computer-controlled micromanipulator.
      Under basal conditions ova exhibited a calcium net efflux of 20.6 +/- 5.2
      fmol/cm2 per sec (n = 69). Treatment of ova with ethanol (7%) or thapsigargin (25
      nM-2.5 microM) transiently increased intracellular calcium and stimulated calcium
      efflux that paralleled levels of [Ca2+]i. The presence of a Na+/Ca2+ exchanger
      was indicated by experiments employing both bepridil, an inhibitor of Na+/Ca2+
      exchange, and sodium-depleted media. In the presence of bepridil, a net influx of
      calcium was revealed across the zona pellucida, which was reflected by an
      increase in the [Ca2+]i. In addition, replenishment of extracellular sodium to
      ova that had been incubated in sodium-depleted media induced a large calcium
      efflux, consistent with the actions of Na+/Ca2+ exchange. Sodium/calcium exchange
      in mouse ova may be an important mechanism that regulates [Ca2+]i.

PMID- 10208976
TI  - Death receptor Fas/Apo-1/CD95 expressed by human placental cytotrophoblasts does
      not mediate apoptosis.
AB  - Trophoblasts, the fetal cells that line the villous placenta and separate
      maternal blood from fetal tissue, express both Fas antigen and the tumor necrosis
      factor (TNF) receptor p55 (TNFRp55), two members of the TNF receptor family that
      contain a cytoplasmic "death domain" that mediates apoptotic signals. We show
      that Fas mRNA expressed by cultured villous cytotrophoblasts isolated from term
      placentas encodes transmembrane sequences and that the protein is full-length
      (approximately 45 kDa), suggesting that the product is an active plasma membrane
      anchored receptor. Its location on the cell surface was confirmed by cellular
      ELISA analysis of live cells. Although cytotrophoblast apoptosis was induced by
      TNFalpha, and both anti-Fas antibody (CH11) and FasL-expressing T lymphocyte
      hybridoma (activated A1.1) cells induced HeLa cell apoptosis, neither CH11
      antibody nor activated A1.1 cells stimulated apoptosis in term or first-trimester
      cytotrophoblasts or in term syncytiotrophoblasts. We conclude that Fas- but not
      TNFRp55-mediated apoptosis is blocked in primary villous trophoblasts. These data
      suggest that the Fas response is specifically inactivated by unknown mechanisms
      to avoid autocrine or paracrine killing by Fas ligand constitutively expressed on
      neighboring cyto- or syncytiotrophoblasts.

PMID- 10208977
TI  - Fatty-acid amide hydrolase is expressed in the mouse uterus and embryo during the
      periimplantation period.
AB  - Arachidonoylethanolamide (anandamide) is an endogenous ligand for cannabinoid
      receptors. We demonstrated previously that the periimplantation mouse uterus has
      high levels of anandamide and can synthesize and hydrolyse anandamide. In the
      present investigation, we examined the expression of the recently identified
      fatty-acid amide hydrolase (FAAH) gene, which is involved in hydrolyzing
      anandamide to arachidonic acid and ethanolamine, in the periimplantation mouse
      embryo and uterus. As previously reported, Northern blot hybridization detected a
      transcript of approximately 2.5 kilobases of FAAH mRNA in whole uterine poly(A)+
      RNA samples. The levels of this mRNA were higher in the liver and brain than in
      the uterus. In the uterus, higher accumulation of FAAH mRNA occurred on Days 1-4
      followed by declines on later days (Days 5-8) of pregnancy. In situ hybridization
      detected this mRNA primarily in uterine luminal and glandular epithelial cells on
      Days 1-4 of pregnancy. With the progression of implantation (Days 5-8),
      accumulation of this mRNA was retained in the luminal and glandular epithelia. In
      addition, implanting blastocysts showed accumulation of this mRNA. FAAH mRNA
      accumulation was absent or minimal in the myometrium during this period. Western
      blotting detected an approximately 60-kDa protein in uterine membrane
      preparations. In preimplantation embryos, FAAH mRNA was present in one-cell and
      two-cell embryos but was absent in embryos at the eight-cell/morula stage.
      However, this mRNA was again detected in Day 4 blastocysts. The presence of FAAH
      mRNA in one- and two-cell embryos reflects accumulation of maternal message,
      while its presence in blastocysts reflects embryonic gene activation.
      Collectively, our present and previous results provide evidence that FAAH is
      expressed in the mouse uterus and embryo during early pregnancy to modulate local
      levels of anandamide that could be important for embryo development and
      implantation.

PMID- 10208978
TI  - Progesterone via its receptor antagonizes the pro-inflammatory activity of
      estrogen in the mouse uterus.
AB  - Populations of macrophages and neutrophils in the uterus are under the control of
      the female sex steroids estrogen and progesterone (P4). Their influx is induced
      by estrogen, while P4 can both stimulate and inhibit leukocyte influx depending
      on the timing of P4 with respect to estrogen. Regulation of leukocytes has been
      implicated in changes in uterine immune responses during the estrous cycle,
      pregnancy, and implantation. This work demonstrates that P4 given concurrently
      with estrogen to ovariectomized mice for 4 days antagonizes the ability of
      estrogen to recruit macrophages and neutrophils into the mouse uterus. Using
      progesterone receptor knockout (PRKO) mice, we show that this effect is dependent
      on progesterone receptors (PR). In the absence of PR, neutrophils recruited by
      estrogen were found to be degranulated, partially explaining the edema that is
      observed with long-term treatment of PRKO mice with estrogen and P4. Populations
      of B lymphocyte cells were shown to be unchanged by estrogen and P4 treatment in
      both wild-type and PRKO mice. The neutrophil chemotactic chemokine MIP-2 was
      examined for down-regulation by P4 but was found to be unaffected by hormonal
      treatment. Together, these observations demonstrate that PR has a strong anti
      inflammatory role in the mouse uterus when estrogen and P4 are present together.

PMID- 10208979
TI  - Plasmin cleaves tumor necrosis factor alpha exodomain from sheep follicular
      endothelium: implication in the ovulatory process.
AB  - Ovulation in the sheep is predicated on plasmin up-regulation at the ovarian
      surface-follicular interface, release of tumor necrosis factor (TNF) alpha from
      contiguous endothelium, and apoptotic cell death. The objectives of this
      investigation were to determine whether plasmin elicits TNFalpha secretion from
      thecal endothelium of ovine follicles, to characterize the site(s) of enzymatic
      attack, and to assess the physiological consequence of soluble TNFalpha action.
      Endothelial cells of thecal tissues isolated from antral follicles of eCG-primed
      anestrous ewes shed (histochemical depletion) TNFalpha into incubation medium
      (ovarian cell DNA fragmentation bioassay, Western blot detection) upon exposure
      to plasmin. Immunopurification and N-terminal sequence analysis indicated that
      TNFalpha was excised from its transmembrane precursor at the Arg79-Ser80 and
      Lys88-Pro89 linkages. Microinjection of TNFalpha into the apical wall of
      explanted follicles induced cellular apoptosis and stigma development. We suggest
      that plasmin-mediated cleavage of TNFalpha exodomain from its membrane anchor
      along thecal endothelium is a determinant of tissue dissolution within the
      formative ovulatory rupture site of ewes.

PMID- 10208980
TI  - Tissue-specific expression of messenger ribonucleic acids for insulin-like growth
      factors and insulin-like growth factor-binding proteins during perinatal
      development of the rat uterus.
AB  - Insulin-like growth factor (IGF)-I and IGF-II play a number of important roles in
      growth and differentiation, and IGF-binding proteins (IGFBPs) modulate IGF
      biological activity. IGF-I has been shown previously to be essential for normal
      uterine development. Therefore, we used in situ hybridization assays to
      characterize the unique tissue- and developmental stage-specific pattern of
      expression for each IGF and IGFBP gene in the rat uterus during perinatal
      development (gestational day [GD]-20 to postnatal day [PND]-24). IGF-I and IGFBP
      1 mRNAs were expressed in all uterine tissues throughout this period. IGFBP-3
      mRNA was not detectable at GD-20 but became detectable beginning at PND-5, and
      the signal intensity appeared to increase during stromal and muscle development.
      IGFBP-4 mRNA was abundant throughout perinatal development in the myometrium and
      in the stroma, particularly near the luminal epithelium. IGFBP-5 mRNA was
      abundantly expressed in myometrium throughout perinatal development. IGFBP-6 mRNA
      was detected throughout perinatal development in both the stroma and myometrium
      in a diffuse expression pattern. IGF-II and IGFBP-2 mRNAs were not detected in
      perinatal uteri. Our results suggest that coordinated temporal and spatial
      expression of IGF-I and its binding proteins (IGFBP-1,-3,-4,-5, and -6) could
      play important roles in perinatal rodent uterine development.

PMID- 10208981
TI  - Expression of hepatocyte growth factor in cultured human endometrial stromal
      cells is induced through a protein kinase C-dependent pathway.
AB  - To examine the production of hepatocyte growth factor (HGF) by human endometrial
      stromal cells (ESC) in vitro, concentrations of HGF in the culture media of ESC
      were measured after the addition of various amounts of 12-O-tetradecanoylphorbol
      13-acetate (TPA), forskolin, lipopolysaccharide (LPS), interleukin (IL)-1beta, IL
      6, IL-8, tumor necrosis factor alpha (TNFalpha), interferon-gamma (IFNgamma), or
      ethynylestradiol-17alpha using an ELISA. The expression of HGF mRNA was also
      assayed by a reverse transcription-polymerase chain reaction. The concentration
      of HGF in the culture media of unstimulated ESC was below the detection level of
      the assay. TPA stimulated the secretion of HGF by ESC in a dose-dependent manner.
      TPA also induced the transcription of HGF mRNA by ESC. Forskolin, LPS, IL-1beta,
      IL-6, IL-8, TNFalpha, IFNgamma, or ethynylestradiol-17alpha did not alter HGF
      mRNA or protein levels. TPA-stimulated production of HGF was partially inhibited
      by the addition of 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine or sphingosine.
      These results suggest that a protein kinase C-dependent pathway may play an
      important role in the regulation of HGF production by ESC. HGF secreted by ESC
      may be involved in the regeneration of the endometrium during the normal
      menstrual cycle.

PMID- 10208982
TI  - Estimates of mouse oviductal fluid tonicity based on osmotic responses of
      embryos.
AB  - Zygotes and early cleavage-stage embryos are very sensitive to increased
      osmolality in vitro, although the tonicity of their in vivo environment,
      oviductal fluid, is unknown. A preference for low osmolality in vitro might imply
      similar conditions in vivo or be specific to culture. Previous electron probe x
      ray microanalysis measurements of total ion content predicted oviductal fluid
      osmolalities of 310-360 mOs/kg, higher than osmolalities tolerated by mouse
      zygotes in vitro. However, such indirect estimates may not reflect the tonicity
      experienced by embryos. We have now used embryos themselves as osmosensors to
      determine the tonicity of mouse oviductal fluid. In one method, we measured the
      mean volume of zygotes in undiluted oviductal fluid and compared this to the mean
      volumes measured for zygotes in media spanning a range of osmolalities. The
      osmolality corresponding to the measured mean volume in oviductal fluid was taken
      to be isotonic. In another, independent method, the sizes of zygotes and two-cell
      embryos were measured as a function of time beginning immediately after removal
      from oviducts. The osmolality in which the embryos neither swelled nor shrank was
      taken to be isotonic. Both methods yielded approximately the same range for the
      tonicity of oviductal fluid: around 290-300 mOs/kg.

PMID- 10208983
TI  - Gender preselection in cattle with intracytoplasmically injected, flow
      cytometrically sorted sperm heads.
AB  - We investigated the development to the blastocyst and subsequent live-offspring
      stages of in vitro-matured bovine oocytes intracytoplasmically injected with flow
      cytometrically sorted bull sperm heads. Bull sperm heads, prepared by ultrasound
      sonication, were distinguished and sorted on the basis of their relative DNA
      contents using a flow cytometer/cell sorter modified for sorting sperm. By
      fluorescence in situ hybridization, the proportion of sperm confirmed as having Y
      specific DNA in the fraction sorted for the Y sperm was 82%. Injection with
      single sorted sperm heads of in vitro-matured oocytes (cultured for 24 h)
      resulted in 46.6% cleavage and 6.9% blastocyst development rates. Embryo transfer
      of 48 blastocysts (Days 7-8) to recipients (one per recipient) resulted in 20.8%
      pregnancy and 20.8% normal live offspring production rates. The birth of 8 male
      and 2 female calves represents an 80% sex preselection accuracy rate.

PMID- 10208984
TI  - Nonpregnant sheep uterine type I and type III nitric oxide synthase expression is
      differentially regulated by estrogen.
AB  - The aim of this study was to characterize the effect of estrogen on the
      expression of neuronal and endothelial isoforms of nitric oxide (NO) synthase
      (NOS) in myometrium, endometrium, and caruncle (nonglandular endometrium) in
      nonpregnant sheep. Twenty sheep were castrated during synchronized estrus (Days
      14-16) and 4 days after surgery treated i.v. through the jugular with 100
      microg/day of estradiol-17beta for 5 (n = 6) or 8 (n = 6) days or with vehicle (n
      = 8). Nitric oxide synthase mRNA was measured by ribonuclease protection assay,
      and NOS protein mass was measured by Western immunoblotting. Data were analyzed
      by ANOVA and Tukey's test. The three distinct uterine compartments studied
      contained the mRNA and protein for the neuronal (type I NOS) and the endothelial
      (type III NOS) isoforms of NOS. However, no inducible NOS was detected. Estrogen
      exhibited a differential effect on NOS expression in a tissue compartment- and
      NOS isoform-specific manner. In myometrium and caruncles, but not in endometrium,
      type I NOS mRNA and protein mass increased significantly (p < 0.05) after 5 or 8
      days of estrogen. In contrast, type III NOS increased significantly in myometrium
      only after 8 days, whereas in endometrium and caruncles the increase was
      significant in the 5-day treatment group (p < 0.05). We conclude that the
      expression of type I NOS and type III NOS in the uterus are differentially
      regulated by estrogen. This differential regulation suggests that the NO produced
      within the uterus serves more than one physiological role. In myometrium it may
      be a uterorelaxant and regulate glucose utilization, and in endometrium and
      myometrium it may regulate blood flow.

PMID- 10208985
TI  - Estrogen responses in bovine fetal uterine cells involve pathways directed by
      both estrogen response element and activator protein-1.
AB  - Objectives were to examine possible roles of estrogen receptor (ER) in
      development of the bovine uterine endometrium in the context of ER type, enhancer
      type, and ligand-independent activation. Expression vectors producing either
      ERalpha or ERbeta were introduced into fetal uterine cells from Day 110 to 120 of
      gestation (UBF120 cells) and into rat embryo fibroblasts (Rat-1 cells), neither
      of which express endogenous ER. Reporter constructs containing either an estrogen
      response element (ERE) or activator protein-1 (AP-1) response element were
      cotransfected. These reporters were also transfected into fetal uterine cells
      from Day 180 to 200 of gestation (UBF180 cells), which express ER. In UBF120 and
      Rat-1 cells transfected with either ERalpha or ERbeta, treatment with estradiol
      17beta (E2) resulted in increased activity of an ERE reporter construct, but not
      an AP-1 element reporter construct. The antiestrogen ICI 182,780 (ICI) exhibited
      E2 antagonist activity with both ERalpha and ERbeta. Thus, all components were
      present for E2-dependent transcription from an ERE except ER; however, cells were
      not competent for E2-dependent transcription mediated through AP-1. In UBF180
      cells, E2 treatment increased both ERE and AP-1 reporter activity. ICI exhibited
      E2 antagonist activity. Treatment with epidermal growth factor resulted in
      increased ERE reporter activity that was inhibited by ICI, indicative of ligand
      independent activation of ER. These data suggest that multiple pathways for ER
      mediated gene regulation occur in the developing fetal uterus and that nuclear
      components necessary for action of both ERalpha and ERbeta are present prior to
      expression of the receptor.

PMID- 10208986
TI  - Does formyl-methionyl-leucyl-phenylalanine exert a physiological role in labor in
      women?
AB  - The classical chemotactic receptor for N-formyl peptides has traditionally been
      associated with polymorphonuclear and mononuclear phagocytes; however, several
      recent reports indicate that this receptor is also expressed in non-myeloid
      cells. In this study we have investigated the presence of binding sites for
      formyl-methionyl-leucyl-phenylalanine (fMLP) in human amniotic membranes of
      laboring and nonlaboring women; we have also evaluated the effect of the peptide
      on prostaglandin E (PGE) release from the same tissue. Our results demonstrate
      the presence of specific, saturable binding sites for 3H-fMLP; Scatchard plot
      analysis suggests the presence of both high- and low-affinity binding sites in
      laboring amnion, while only the low-affinity receptors were evident in
      nonlaboring tissue. N-t-butoxycarbonyl-methionyl-leucyl-phenylalanine (Boc-MLP),
      a formyl peptide receptor antagonist, inhibited 3H-fMLP binding in both
      preparations. In addition, fMLP was able to significantly increase PGE synthesis
      in perifused amnion fragments from laboring and nonlaboring women. This effect
      was counteracted by Boc-MLP treatment. The presence of specific binding sites for
      fMLP in amniotic tissue and their differing expression in laboring versus
      nonlaboring membranes, together with the action of the peptide on PGE synthesis,
      all suggest a physiological role for fMLP in labor.

PMID- 10208987
TI  - In vitro nitric oxide effects on basal and gonadotropin-releasing hormone-induced
      gonadotropin secretion by pituitary gland of male crested newt (Triturus
      carnifex) during the annual reproductive cycle.
AB  - The objective of this study was to test the possible nitric oxide (NO)
      involvement in pituitary gonadotropin secretion in the male crested newt,
      Triturus carnifex. Pituitaries were incubated in vitro with medium alone, GnRH,
      NO donor (NOd, sodium nitroprusside), NO synthase inhibitor (NOSi, Nomega-nitro-L
      arginine methyl ester), cGMP analogue (cGMPa, 8-bromo-cGMP), soluble guanylate
      cyclase inhibitor (sGCi, cystamine), GnRH plus NOSi, GnRH plus sGCi, and NOd plus
      sGCi during the annual reproductive cycle: pre-reproduction, reproduction
      (noncourtship and courtship), and the refractory, recovery, and estivation
      periods. To determine pituitary gonadotropin secretion indirectly, newt testes
      were superfused in vitro with preincubated pituitaries, and androgen release was
      determined. NO synthase (NOS) activity and cGMP levels were assessed in the
      preincubated pituitaries. Medium alone- and GnRH-preincubated pituitary increased
      androgen secretion during pre-reproduction, noncourtship, courtship, and
      recovery; the GnRH-induced increase was higher than the medium alone-induced
      increase during pre-reproduction, noncourtship, and recovery. NOd and cGMPa
      increased androgens in all reproductive phases considered except courtship; the
      NOd- and cGMP-induced increase was higher than the medium alone-induced increase
      during pre-reproduction, noncourtship, and recovery. NOS activity was highest
      during courtship and lowest during the refractory and estivation periods. GnRH
      increased NOS activity during pre-reproduction, noncourtship, and recovery.
      Cyclic GMP levels were highest during courtship and lowest during the refractory
      period and estivation. GnRH increased cGMP levels during pre-reproduction,
      noncourtship, and recovery, while NOd did so during all reproductive phases
      considered. These results suggest that basal and GnRH-induced gonadotropin
      secretion are up-regulated by NO in the pituitary gland of the male Triturus
      carnifex.

PMID- 10208988
TI  - Differential regulation of the gonadotropin storage pattern by gonadotropin
      releasing hormone pulse frequency in the ewe.
AB  - The differential control of gonadotropin secretion by GnRH pulse frequency may
      reflect changes in the storage of LH and FSH. To test this hypothesis,
      ovariectomized ewes passively immunized against GnRH received pulsatile
      injections of saline (group 1) or GnRH analogue: 1 pulse/6 h for group 2 or 1
      pulse/h for group 3, during 48 h. Immunization against GnRH suppressed
      pulsatility of LH release and reduced mean FSH plasma levels (3.1 +/- 0.2 vs. 2.2
      +/- 0.1 ng/ml before and 3 days after immunization, respectively). Pulsatile GnRH
      analogue replacement restored LH pulses but not FSH plasma levels. Low and high
      frequencies of GnRH analogue increased the percentage of LH-containing cells in a
      similar way (group 1 = 6.9 +/- 0.5% vs. group 2 = 10.5 +/- 0.8%, or vs. group 3 =
      9.6 +/- 0.4%). In contrast, the rise of the percentage of FSH-containing cells
      was greater after administration of the analogue at low frequency than at high
      frequency (group 1 = 3.7 +/- 0.4% vs. group 2 = 8.4 +/- 0.2%, or vs. group 3 =
      5.2 +/- 0.8%). Moreover, while GnRH pulse frequency had no differential effect on
      FSHbeta mRNA levels, LHbeta mRNA levels were higher under high than low
      frequency. These data showed that the frequency of GnRH pulses can modulate the
      gonadotropin storage pattern in the ewe. These changes may be a component of the
      differential regulation of LH and FSH secretion.

PMID- 10208989
TI  - Utilization of endoscopic inoculation in a mouse model of intrauterine infection
      induced preterm birth: role of interleukin 1beta.
AB  - A novel murine model of intrauterine infection/inflammation-induced preterm birth
      based on direct endoscopic intracervical inoculation is described. Using this
      model, we investigated infection-induced premature pregnancy loss in normal and
      interleukin (IL) 1beta-deficient mice. Seventy-four CD-1, HS, C57BL/6J wild type
      (IL-1beta+/+), and C57BL/6J IL-1beta-deficient (IL-1beta-/-) mice were inoculated
      intracervically using a micro-endoscope, at a time corresponding to 70% of
      average gestation. Intracervical injection of lipopolysaccharide (LPS) or
      Escherichia coli reliably induced premature birth: 100% of mice intracervically
      injected with LPS and 92% of mice with a positive endometrial E. coli culture
      delivered prematurely within 36 h after inoculation. No losses were observed in
      mice inoculated with saline. Pregnancy loss was associated with increased uterine
      tissue cyclooxygenase-2 gene expression and uterine content of IL-1beta, tumor
      necrosis factor alpha, macrophage inflammatory protein-1alpha, and IL-6, as well
      as elevation of nuclear factor-kappaB activity in uterine tissues. Although IL
      1beta-/- mice exhibited decreased uterine cytokine production in response to
      bacteria and LPS, IL-1beta deficiency did not affect the rate of pregnancy loss.
      This model using direct intracervical bacterial or LPS inoculation is useful for
      studying preterm pregnancy loss in genetically altered mice in order to develop
      novel interventions for infection-associated preterm labor.

PMID- 10208990
TI  - Protein tyrosine phosphorylation during hyperactivated motility of cynomolgus
      monkey (Macaca fascicularis) spermatozoa.
AB  - Capacitation and capacitation-related hyperactivated motility do not occur
      spontaneously in cynomolgus monkey (Macaca fascicularis) spermatozoa; instead,
      both have an absolute requirement for exogenous stimulation with caffeine and
      dibutyryl (db)cAMP. In the present study, we 1) defined sorting criteria for
      automated analysis of macaque sperm exhibiting hyperactivated motility (HA) and
      2) investigated protein tyrosine phosphorylation involvement in dbcAMP- and
      caffeine-stimulated capacitation and HA. Motion characteristics were assessed by
      computer-assisted motion analysis. Tyrosine phosphorylation of sperm tail
      proteins was determined by immunocytochemistry with PY-20 antiserum. Automated
      sorting criteria for HA were curvilinear velocity (VCL) >/= 150 microm/sec;
      amplitude of lateral head displacement (ALH) >/= 8.0 microm, and linearity (LIN)
      </= 60%. Using these criteria, caffeine and dbcAMP significantly stimulated HA
      (61 +/- 8%) compared to control conditions (12 +/- 2%), p < 0.01, with a
      concomitant increase in PY-20 labeling (88 +/- 12%) vs. control (13 +/- 2%), p <
      0.01. PY-20 labeling significantly correlated with HA (r = 0.75, p < 0.01) and
      with some motion characteristics used for HA sorting including ALH (r = 0.86, p =
      0.0013) and LIN (r = -0.88, p < 0.001) but not VCL (r = 0.21). Treatment with
      genistein (10 microM) had no effect on HA or PY-20 immunocytochemistry in the
      absence of caffeine and dbcAMP, but the tyrosine kinase inhibitor significantly
      decreased caffeine- and dbcAMP-stimulated HA and PY-20 labeling in a dose
      dependent manner (p < 0.01). These results demonstrate that tyrosine
      phosphorylation of sperm tail proteins is an integral signaling pathway
      modulating some but not all of the motion characteristics associated with cAMP-
      and caffeine-stimulated HA in cynomolgus monkey spermatozoa.

PMID- 10208991
TI  - Expression of the basic helix-loop-helix protein REBalpha in rat testicular
      Sertoli cells.
AB  - Sertoli cell differentiation is initiated in the embryo to promote testicular
      development and male sex determination. In the adult, Sertoli cells are critical
      for maintenance of the spermatogenic process. Previously, Sertoli cell
      differentiation has been shown to be regulated in part by basic helix-loop-helix
      (bHLH) transcription factors. This was based on the observation that promoters of
      a number of Sertoli cell genes contained bHLH-responsive E-box response elements
      and that overexpression of Id, a negatively acting HLH protein, down-regulates
      Sertoli cell differentiated functions. Analysis of Sertoli cell bHLH proteins
      demonstrated the expression of REBalpha in Sertoli cells. REBalpha and REBbeta
      are spliced variants of the REB gene that is implicated in cell-specific gene
      expression as part of dimeric bHLH complexes acting on E-box response elements.
      Although both the transcripts of the REB gene are widely expressed, differential
      expression of the REB gene transcripts REBalpha and REBbeta has been shown. In
      the current study, a polymerase chain reaction (PCR)-based approach demonstrated
      that REB gene transcripts are expressed in the testis. Characterization of the
      REB transcripts suggested that REBalpha is the major splice variant in Sertoli
      cells. PCR primers specifically designed to amplify either REBalpha or REBbeta
      demonstrated that Sertoli cells express only REBalpha, not REBbeta. REBbeta was
      present in the RNA samples obtained from whole testis, suggesting expression in
      other testicular cell types. A Northern blot analysis of RNA from Sertoli cells
      treated with or without FSH or cAMP demonstrated that REBalpha is not hormone
      responsive. REBalpha was also found to be expressed in germ cells and peritubular
      cells. An immunocytochemical analysis demonstrated that REBalpha is predominantly
      expressed by Sertoli cells within the seminiferous tubules. The activity of
      REBalpha in Sertoli cells was demonstrated with an E-box gel shift with Sertoli
      cell nuclear extracts. The E-box gel shift was found to contain REBalpha and
      E47/E12 bHLH proteins. In summary, the Sertoli cell is one of the first cells
      shown to specifically express the REBalpha isoform of the REB gene. The results
      are discussed in relation to the possibility that Sertoli cells may express a
      cell-specific bHLH protein that can preferentially dimerize with REBalpha.

PMID- 10208992
TI  - Androgen receptor messenger ribonucleic acid in brains and pituitaries of male
      rhesus monkeys: studies on distribution, hormonal control, and relationship to
      luteinizing hormone secretion.
AB  - Because the distribution and hormonal regulation of the androgen receptor (AR)
      mRNA in brains and pituitaries of adult rhesus monkeys have not been studied, we
      cloned and sequenced a 329-base pair segment of the 5' coding region of the
      rhesus AR cDNA. Monkey AR cDNA was 99% identical with the human sequence and 96%
      homologous with the rat sequence. Using a ribonuclease protection assay, we
      studied the distribution and regulation of AR mRNA in brains and anterior
      pituitary glands of three groups of male rhesus monkeys: intact (n = 3),
      castrated (Cx, n = 4), and Cx treated with testosterone (n = 6). Serum
      testosterone levels of Cx males treated with testosterone differed significantly
      (p < 0.05) in the morning but not in the evening hours from those in intact
      controls. Serum LH concentrations were significantly suppressed (p < 0.05) in
      both morning and evening serum samples of testosterone-treated males compared to
      intact controls. We found the highest concentrations of AR mRNA in the medial
      basal hypothalamus, the bed nucleus of the stria terminalis, the medial preoptic
      area-anterior hypothalamus, and the lateral dorsomedial hypothalamus.
      Intermediate amounts were found in the septum and amygdala. Low amounts were
      found in the hippocampus, cingulate cortex, parietal cortex, and cerebellum. The
      anterior pituitary gland also contained a large amount of AR mRNA. Surprisingly,
      neither Cx for 3 wk nor Cx plus testosterone replacement for 3 wk significantly
      affected AR mRNA in any brain area or in the pituitary gland. The present study
      demonstrates that the effectiveness of testosterone as a regulator of LH
      secretion in male monkeys is not related to changes of AR mRNA in the brain or
      pituitary gland. It appears that AR mRNA in the monkey brain and pituitary gland
      is not regulated at the transcriptional level by androgen.

PMID- 10208993
TI  - Calcium/phospholipid-dependent protein kinases in rat Sertoli cells: regulation
      of androgen receptor messenger ribonucleic acid.
AB  - The possibility that Sertoli cell responses to testosterone are modulated by the
      calcium/phospholipid-dependent protein kinase (protein kinase C; PKC) was
      examined in rat Sertoli cells in culture. Both soluble and particulate cell
      fractions showed low constitutive phosphotransferase activity. Incubation with
      the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA; 10(-7) M) was
      associated with a transient induction in both cell fractions of
      calcium/phosphatidylserine-dependent PKC activity, which was elevated from 15 min
      to 1 h. Consistent with this, mRNAs for the calcium/phospholipid-dependent
      isomeric forms of PKC (alpha, beta, and gamma) were detected. The expression
      levels of mRNAs for PKCalpha and PKCbeta were also up-regulated (2.5- to 3-fold)
      by TPA (10(-7) M), but these effects were much slower (peaking after 12 h) than
      those on phosphotransferase activity. In the presence of TPA (10(-7) M),
      expression of androgen receptor (AR) mRNA showed a transient time-dependent down
      regulation ( approximately 70%), in which the nadir was reached after 6 h and
      baseline expression was again obtained after 12 h. The regulatory effect of PKC
      activation on AR mRNA was confirmed by the absence of response to a biologically
      inactive phorbol ester. A concentration-dependent decrease (half-maximal effect
      at approximately 10(-8) M TPA) of AR mRNA was also observed. These data suggest
      that Sertoli cell responses to testosterone may be inhibited by a transiently
      active PKC with a wide intracellular distribution.

PMID- 10208994
TI  - Defects in the germ line and gonads of mice lacking connexin43.
AB  - The connexins are a family of at least 15 proteins that form the intercellular
      membrane channels of gap junctions. Numerous connexins, including connexin43
      (Cx43), have been implicated in reproductive processes by virtue of their
      expression in adult gonads. In the present study, we examined the gonads of fetal
      and neonatal mice homozygous for a null mutation in the Gja1 gene encoding Cx43
      to determine whether the absence of this connexin has any consequences for
      gonadal development. We found that in both sexes at the time of birth, the gonads
      of homozygous mutants were unusually small. This appears to be caused, at least
      in part, by a deficiency of germ cells. The germ cell deficiency was traced back
      as far as Day 11.5 of gestation, implying that it arises during early stages of
      germ line development. We also used an organ culture technique to examine
      postnatal folliculogenesis in the mutant ovaries, an approach necessitated by the
      fact that Gja1 null mutant offspring die soon after birth because of a heart
      abnormality. The results demonstrated that folliculogenesis can proceed to the
      primary (unilaminar) follicle stage in the absence of Cx43 but that subsequent
      development is impaired. In neonatal ovaries of normal mice, Cx43 could be
      detected in the somatic cells as early as Day 1, when primordial follicles begin
      to appear, supporting the conclusion that this connexin is required for the
      earliest stages of folliculogenesis. These results imply that gap junctional
      coupling mediated by Cx43 channels plays indispensable roles in both germ line
      development and postnatal folliculogenesis.

PMID- 10208995
TI  - Frequency of atrial septal aneurysms in patients with cerebral ischemic events.
AB  - BACKGROUND: Atrial septal aneurysm (ASA) is a putative risk factor for
      cardioembolism. However, the frequency of ASA in the general population has not
      been adequately determined. Therefore, the frequency in patients with cerebral
      ischemic events, compared with the frequency in the general population, is poorly
      defined. We sought to determine the frequency of ASA in the general population
      and to compare the frequency of ASA in patients with cerebral ischemic events
      with the frequency in the general population. METHODS AND RESULTS: The frequency
      of ASA in the population was determined in 363 subjects, a sample of the
      participants in the Stroke Prevention: Assessment of Risk in a Community study
      (control subjects), and was compared with the frequency in 355 age- and sex
      matched patients undergoing transesophageal echocardiography in search of a
      cardiac source of embolism after a focal cerebral ischemic event. The proportion
      with ASA was 7.9% in patients versus 2.2% in control subjects (P=0.002; odds
      ratio of ASA, 3.65; 95% CI, 1.64 to 8.13, in patients versus control subjects).
      Patent foramen ovale (PFO) was detected with contrast injections in 56% of
      subjects with ASA. The presence of ASA predicted the presence of PFO (odds ratio
      of PFO, 4.57; 95% CI, 2.18 to 9.57, in subjects with versus those without ASA).
      In 86% of subjects with ASA and cerebral ischemia, transesophageal
      echocardiography did not detect an alternative source of cardioembolism other
      than an associated PFO. CONCLUSIONS: The prevalence of ASA based on this
      population-based study is 2.2%. The frequency of ASA is relatively higher in
      patients evaluated with transesophageal echocardiography after a cerebral
      ischemic event. ASA is frequently associated with PFO, suggesting paradoxical
      embolism as a mechanism of cardioembolism. In patients with cerebral ischemia and
      ASA, ASA (with or without PFO) commonly is the only potential cardioembolic
      source detected with transesophageal echocardiography.

PMID- 10208996
TI  - Relationship between TIMI frame count and clinical outcomes after thrombolytic
      administration. Thrombolysis In Myocardial Infarction (TIMI) Study Group.
AB  - BACKGROUND: The corrected TIMI frame count (CTFC) is the number of cine frames
      required for dye to first reach standardized distal coronary landmarks, and it is
      an objective and quantitative index of coronary blood flow. METHODS AND RESULTS:
      The CTFC was measured in 1248 patients in the TIMI 4, 10A, and 10B trials, and
      its relationship to clinical outcomes was examined. Patients who died in the
      hospital had a higher CTFC (ie, slower flow) than survivors (69. 6+/-35.4 [n=53]
      versus 49.5+/-32.3 [n=1195]; P=0.0003). Likewise, patients who died by 30 to 42
      days had higher CTFCs than survivors (66.2+/-36.4 [n=57] versus 49.9+/-32.1
      [n=1059]; P=0.006). In a multivariate model that excluded TIMI flow grades, the
      90-minute CTFC was an independent predictor of in-hospital mortality (OR=1.21 per
      10-frame rise [95% CI, 1.1 to 1.3], an approximately 0.7% increase in absolute
      mortality for every 10-frame rise; P<0.001) even when other significant
      correlates of mortality (age, heart rate, anterior myocardial infarction, and
      female sex) were adjusted for in the model. The CTFC identified a subgroup of
      patients with TIMI grade 3 flow who were at a particularly low risk of adverse
      outcomes. The risk of in-hospital mortality increased in a stepwise fashion from
      0.0% (n=41) in patients with a 90-minute CTFC that was faster than the 95% CI for
      normal flow (0 to 13 frames, hyperemia, TIMI grade 4 flow), to 2.7% (n=18 of 658
      patients) in patients with a CTFC of 14 to 40 (a CTFC of 40 has previously been
      identified as the cutpoint for distinguishing TIMI grade 3 flow), to 6.4%
      (35/549) in patients with a CTFC >40 (P=0.003). Although the risk of death,
      recurrent myocardial infarction, shock, congestive heart failure, or left
      ventricular ejection fraction </=40% was 13.0% among patients with TIMI grade 3
      flow (CTFC </=40), the CTFC tended to segregate patients into lower-risk (CTFC
      </=20, risk of adverse outcome of 7. 9%) and higher-risk subgroups (CTFC >20 to
      </=40, risk of adverse outcome of 15.5%; P=0.17). CONCLUSIONS: Faster (lower) 90
      minute CTFCs are related to improved in-hospital and 1-month clinical outcomes
      after thrombolytic administration in both univariate and multivariate models.
      Even among those patients classified as having normal flow (TIMI grade 3 flow,
      CTFC </=40), there may be lower- and higher-risk subgroups.

PMID- 10208997
TI  - Sustained suppression of ischemic complications of coronary intervention by
      platelet GP IIb/IIIa blockade with abciximab: one-year outcome in the EPILOG
      trial. Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa
      blockade.
AB  - BACKGROUND: Blockade of the platelet glycoprotein IIb/IIIa receptor with the
      monoclonal antibody fragment abciximab was shown in a placebo-controlled
      randomized trial to reduce the incidence of acute ischemic complications within
      30 days among a broad spectrum of patients undergoing percutaneous coronary
      revascularization. The durability of clinical benefit in this setting has not
      been established. METHODS AND RESULTS: A total of 2792 patients enrolled in the
      Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa
      blockade (EPILOG) trial were followed with maintenance of double-blinding for 1
      year. Patients had been assigned at the time of their index coronary
      interventional procedure to receive placebo with standard-dose, weight-adjusted
      heparin (100 U/kg initial bolus), abciximab with standard-dose, weight-adjusted
      heparin, or abciximab with low-dose, weight-adjusted heparin (70 U/kg initial
      bolus). The primary outcome was the composite of death, myocardial infarction, or
      urgent repeat revascularization by 30 days; this composite end point and its
      individual components were also assessed at 6 months and 1 year. Rates of any
      repeat revascularization (urgent or elective), target vessel revascularization,
      and a composite of death, myocardial infarction, or any repeat revascularization
      were also reported. Follow-up at 1 year was 99% complete for survival status and
      97% complete for other end points. By 1 year, the incidence of the primary
      composite end point was 16.1% in the placebo group, 9.6% in the abciximab with
      low-dose heparin group (P<0.001), and 9.5% in the abciximab with standard-dose
      heparin group (P<0.001). Each of the components of this composite end point was
      reduced to a similar extent. Nonurgent or target vessel repeat revascularization
      rates were not significantly decreased by abciximab therapy. Mortality rates over
      1 year increased with increasing levels of periprocedural creatine kinase MB
      fraction elevation. CONCLUSIONS: Acute reductions in ischemic events after
      percutaneous coronary intervention by abciximab are sustained over follow-up to
      at least 1 year. Early periprocedural myocardial infarctions suppressed by this
      therapy are associated with long-term mortality rates.

PMID- 10208998
TI  - Evidence for a new pathophysiological mechanism for coronary artery disease
      regression: hepatic lipase-mediated changes in LDL density.
AB  - BACKGROUND: Small, dense LDL particles are associated with coronary artery
      disease (CAD) and predict angiographic changes in response to lipid-lowering
      therapy. Intensive lipid-lowering therapy in the Familial Atherosclerosis
      Treatment Study (FATS) resulted in significant improvement in CAD. This study
      examines the relationship among LDL density, hepatic lipase (HL), and CAD
      progression, identifying a new biological mechanism for the favorable effects of
      lipid-altering therapy. METHODS AND RESULTS: Eighty-eight of the subjects in FATS
      with documented coronary disease, apolipoprotein B levels >/=125 mg/dL, and
      family history of CAD were selected for this study. They were randomly assigned
      to receive lovastatin (40 mg/d) and colestipol (30 g/d), niacin (4 g/d) and
      colestipol, or conventional therapy with placebo alone or with colestipol in
      those with elevated LDL cholesterol levels. Plasma hepatic lipase (HL),
      lipoprotein lipase, and LDL density were measured when subjects were and were not
      receiving lipid-lowering therapy. LDL buoyancy increased with lovastatin
      colestipol therapy (7.7%; P<0.01) and niacin-colestipol therapy (10.3%; P<0.01),
      whereas HL decreased in both groups (-14% [P<0.01] and -17% [P<0.01] with
      lovastatin-colestipol and niacin-colestipol, respectively). Changes in LDL
      buoyancy and HL activity were associated with changes in disease severity
      (P<0.001). In a multivariate analysis, an increase in LDL buoyancy was most
      strongly associated with CAD regression, accounting for 37% of the variance of
      change in coronary stenosis (P<0.01), followed by reduction in apolipoprotein Bl
      (5% of variance; P<0.05). CONCLUSIONS: These studies support the hypothesis that
      therapy-associated changes in HL alter LDL density, which favorably influences
      CAD progression. This is a new and potentially clinically relevant mechanism
      linking lipid-altering therapy to CAD improvement.

PMID- 10208999
TI  - Thermal heterogeneity within human atherosclerotic coronary arteries detected in
      vivo: A new method of detection by application of a special thermography
      catheter.
AB  - BACKGROUND: Activated macrophages play an important role in the pathogenesis of
      acute ischemic syndromes. It has been postulated that detection of heat released
      by activated inflammatory cells of atherosclerotic plaques may predict plaque
      rupture and thrombosis. Previous ex vivo studies have shown that there is thermal
      heterogeneity in human carotid atherosclerotic plaques. METHODS AND RESULTS: To
      measure the temperature of human arteries in vivo, we developed a catheter-based
      technique. Ninety patients (45 with normal coronary arteries, 15 with stable
      angina [SA], 15 with unstable angina [UA], and 15 with acute myocardial
      infarction [AMI]) were studied. The thermistor of the thermography catheter has a
      temperature accuracy of 0.05 degrees C, a time constant of 300 ms, and a spatial
      resolution of 0.5 mm. Temperature was constant within the arteries of the control
      subjects, whereas most atherosclerotic plaques showed higher temperature compared
      with healthy vessel wall. Temperature differences between atherosclerotic plaque
      and healthy vessel wall increased progressively from SA to AMI patients
      (difference of plaque temperature from background temperature, 0. 106+/-0.110
      degrees C in SA, 0.683+/-0.347 degrees C in UA, and 1. 472+/-0.691 degrees C in
      AMI). Heterogeneity within the plaque was shown in 20%, 40%, and 67% of the
      patients with SA, UA, and AMI, respectively, whereas no heterogeneity was shown
      in the control subjects. CONCLUSIONS: Thermal heterogeneity within human
      atherosclerotic coronary arteries was shown in vivo by use of a special
      thermography catheter. This heterogeneity is larger in UA and AMI, suggesting
      that it may be related to the pathogenesis.

PMID- 10209001
TI  - Predicting sudden death in the population: the Paris Prospective Study I.
AB  - BACKGROUND: Sudden death was found to share the same set of usual risk factors as
      coronary events and therefore could not be specifically predicted in the
      population. It appears, however, that parental history of sudden death has not
      been investigated yet as a risk factor for sudden death. Therefore, we assessed
      risk factors, including parental sudden death, associated with the occurrence of
      sudden death in a long-term cohort study. METHODS AND RESULTS: We included 7746
      men employed by the city of Paris who were 43 to 52 years of age in 1967 to 1972
      in the Paris Prospective Study I. Each subject underwent a physical examination
      and an ECG, provided blood for laboratory tests, and answered questionnaires
      administered by trained interviewers who paid particular attention to family
      medical history. Men with known ischemic cardiac disease were further excluded
      from analysis. For 95.5% of the men, vital status was obtained from specific
      inquiries until retirement, then by death certificates. Resting heart rate,
      systolic or diastolic blood pressure, tobacco consumption, body mass index,
      diabetes status, serum cholesterol, and parental history of sudden death were
      independent factors associated with sudden death during follow-up (23 years on
      average). When adjusted for confounding variables, including parental history of
      myocardial infarction, relative risk of sudden death associated with parental
      sudden death was 1.80 (95% CI, 1.11 to 2.88). CONCLUSIONS: Parental sudden death
      is an independent risk factor for sudden death in middle-aged men. The existence
      of familial risk factors for sudden death may help provide better identification
      of subjects at high risk of and early prevention of sudden death.

PMID- 10209000
TI  - Determinants and prognostic implications of persistent ST-segment elevation after
      primary angioplasty for acute myocardial infarction: importance of microvascular
      reperfusion injury on clinical outcome.
AB  - BACKGROUND: Despite early recanalization of an occluded infarct artery,
      reperfusion at the level of the microcirculation may remain impaired owing to a
      process of microvascular reperfusion injury. METHODS AND RESULTS: Microvascular
      reperfusion injury was studied in 91 patients with acute myocardial infarction
      (AMI) by evaluation of the resolution of ST-segment elevation after successful
      PTCA. Impaired microvascular reperfusion, defined as the presence of persistent
      (>/=50% of initial value) ST-segment elevation (ST >/=50%) at the end of coronary
      intervention, was observed in 33 patients (36%) and was independently correlated
      with low systolic pressure on admission and high age. Patients >/=55 years of age
      with systolic pressures </=120 mm Hg were at high risk for development of
      impaired reperfusion compared with patients not meeting these criteria (72%
      versus 14%, P<0.001). Impaired microvascular reperfusion was associated with a
      more extensive infarction and worse clinical outcome at the 1-year follow-up:
      cardiac death rate, 15% versus 2% (ST >/=50% versus ST <50%, P=0.01); nonfatal MI
      rate, 9% versus 2% (P=0.1); and total major adverse cardiac event (MACE) rate,
      45% versus 15% (P<0.005). ST >/=50% was the most important independent
      determinant of MACE with an adjusted risk ratio of 3.4. CONCLUSIONS: Impaired
      microvascular reperfusion, as evidenced by ST >/=50% after successful
      recanalization, occurs in more than one third of our AMI patients, especially in
      older patients with low systolic pressure. Its detrimental implications on
      clinical outcome reinforce the need to develop adjunctive agents that attenuate
      the process of reperfusion injury.

PMID- 10209002
TI  - Kallidin- and bradykinin-degrading pathways in human heart: degradation of
      kallidin by aminopeptidase M-like activity and bradykinin by neutral
      endopeptidase.
AB  - BACKGROUND: Since kinins kallidin (KD) and bradykinin (BK) appear to have
      cardioprotective effects ranging from improved hemodynamics to antiproliferative
      effects, inhibition of kinin-degrading enzymes should potentiate such effects.
      Indeed, it is believed that this mechanism is partly responsible for the
      beneficial effects of angiotensin-converting enzyme (ACE) inhibitors. In the
      heart, enzymes other than ACE may contribute to local degradation of kinins. The
      purpose of this study was to investigate which enzymes are responsible for the
      degradation of KD and BK in human heart tissue. METHODS AND RESULTS: Cardiac
      membranes were prepared from the left ventricles of normal (n=5) and failing
      (n=10) hearts. The patients had end-stage congestive heart failure as the result
      of coronary heart disease or idiopathic dilated cardiomyopathy. Heart tissue was
      incubated with KD or BK in the presence or absence of enzyme inhibitors. We found
      no difference in the enzymes responsible for kinin metabolism or their activities
      between normal and failing hearts. Thus KD was mostly converted into BK by the
      aminopeptidase M-like activity. When BK was used as substrate, it was converted
      into an inactive metabolite BK-(1-7) mostly (80% to 90%) by the neutral
      endopeptidase (NEP) activity, with ACE unexpectedly playing only a minor role.
      The low enzymatic activity of ACE in the cardiac membranes, compared with that of
      NEP, was not due to chronic ACE inhibitor therapy, because the cardiac ACE
      activities of patients, whether receiving ACE inhibitors or not, and of normal
      subjects were all equal. CONCLUSIONS: The present in vitro study shows that in
      human cardiac membranes, the most critical step in kinin metabolism, that is,
      inactivation of BK, appears to be mediated mostly by NEP. This observation
      suggests a role for NEP in the local control of BK concentration in heart tissue.
      Thus inhibition of cardiac NEP activity could be cardioprotective by elevating
      the local concentration of BK in the heart.

PMID- 10209003
TI  - Relationship between left ventricular mass and endothelium-dependent vasodilation
      in never-treated hypertensive patients.
AB  - BACKGROUND: Hypertensive patients are characterized by development of both left
      ventricular hypertrophy (LVH) and endothelial dysfunction METHODS AND RESULTS: We
      enrolled 65 never-treated hypertensive patients (36 men and 29 women aged 45.6+/
      6.0 years) to assess the possible relationship between echocardiographic left
      ventricular mass (LVM) and endothelium-dependent vasodilation. Left ventricular
      measurements were performed at end diastole and end systole according to the
      recommendations of the American Society of Echocardiography and the Penn
      Convention. LVM was calculated with the Devereux formula and indexed by body
      surface area and height raised to the 2.7th power. The endothelial function was
      tested as responses of forearm vasculature to acetylcholine (ACh), an endothelium
      dependent vasodilator (7.5, 15, and 30 microg. mL-1. min-1, each for 5 minutes),
      and sodium nitroprusside (SNP), an endothelium-independent vasodilator (0.8, 1.6,
      and 3.2 microg. mL-1. min-1, each for 5 minutes). Drugs were infused into the
      brachial artery, and forearm blood flow (FBF) was measured by strain-gauge
      plethysmography. A negative significant relationship between indexed LVM and peak
      of increase in FBF was found during ACh infusions (r=-0. 554; P<0.0001). In
      addition, hypertrophic patients had a significantly lower responsive to ACh than
      patients without LVH (the peak increase in FBF was 9.9+/-3.7 versus 16.1+/-8.1 mL
      per 100 mL of tissue per minute; P<0.0001). No significant correlation was
      observed between LVM and FBF during SNP infusion. CONCLUSIONS: Our data provide
      the first evidence that echocardiographic LVM in hypertensive patients is
      inversely related to FBF responses to the endothelium-dependent vasodilating
      agent ACh, but it is likely that both endothelium and LVM are damaged by
      hypertension.

PMID- 10209004
TI  - Antiphospholipid antibodies from antiphospholipid syndrome patients activate
      endothelial cells in vitro and in vivo.
AB  - BACKGROUND: Antiphospholipid (aPL) antibodies are associated with thrombosis in
      patients diagnosed with antiphospholipid syndrome (APS) and enhance thrombus
      formation in vivo in mice, but the mechanism of thrombosis by aPL is not
      completely understood. Although aPL antibodies have been shown to inhibit protein
      C activation and activate endothelial cells (ECs) in vitro, no study has examined
      whether these antibodies activate ECs in vivo. Therefore, human affinity-purified
      aPL (ap aPL) antibodies from APS patients were tested in a mouse model of
      microcirculation using the cremaster muscle that allows direct microscopic
      examination of thrombus formation and adhesion of white blood cells (WBCs) to ECs
      as an indication of EC activation in vivo. Adhesion molecule expression on human
      umbilical vein endothelial cells (HUVECs) after aPL exposure was performed to
      confirm EC activation in vitro. METHODS AND RESULTS: All 6 ap aPL antibodies
      significantly increased the expression of VCAM-1 (2.3- to 4.4-fold), with one of
      the antibodies also increasing the expression of E-selectin (1.6-fold) on HUVECs
      in vitro. In the in vivo experiments, each ap aPL antibody except for 1
      preparation increased WBC sticking (mean number of WBCs ranged from 22.7 to 50.6)
      compared with control (14.4), which correlated with enhanced thrombus formation
      (mean thrombus size ranged from 1098 to 6476 versus 594 microm2 for control).
      CONCLUSIONS: Activation of ECs by aPL antibodies in vivo may create a
      prothrombotic state on ECs, which may be the first pathophysiological event of
      thrombosis in APS.

PMID- 10209005
TI  - Intracranial arteries of human fetuses are more resistant to hypercholesterolemia
      induced fatty streak formation than extracranial arteries.
AB  - BACKGROUND: Atherosclerotic lesions in intracranial arteries occur later and are
      less extensive than in extracranial arteries. To investigate potential mechanisms
      responsible for this difference, in particular the atherogenic response to
      hypercholesterolemia and LDL oxidation, we compared the extent of fatty streak
      formation and the composition of these very early lesions in intracranial
      arteries of human fetuses from normocholesterolemic and hypercholesterolemic
      mothers with those in extracranial arteries. METHODS AND RESULTS: Lesions were
      quantified by computer-assisted image analysis of 30 oil red O-stained sections,
      each from the middle cerebral, basilar, and common carotid arteries and the
      abdominal aorta of human fetuses (spontaneous abortions and premature newborns
      who died within 12 hours of birth; both of fetal age 6.2+/-1.3 months) from 43
      hypercholesterolemic mothers and 34 normocholesterolemic mothers. Macrophages,
      apolipoprotein B, and 2 epitopes of oxidized LDL in lesions were determined
      immunocytochemically. Activities of superoxide dismutase, catalase, and
      glutathione peroxidase in the arterial wall were also determined. Lesion numbers
      and sizes were dramatically greater in the abdominal aorta (area of the largest
      lesion per section: 66.5+/-10.9 x10(3) microm2) and the carotid (11. 6+/-5.3
      x10(3) microm2) than in the basilar and middle cerebral artery (0.4+/-0.1 and
      0.8+/-0.2 x10(3) microm2, respectively; P<0. 0001). Hypercholesterolemia resulted
      in a significant increase of lesion size in extracranial arteries but only a
      marginal increase in intracranial arteries. In analogy, hypercholesterolemia
      induced a much greater increase in the intimal presence of macrophages,
      apolipoprotein B, and oxidized LDL (oxidation-specific epitopes) in extracranial
      than in intracranial arteries. Immunocytochemistry did not indicate that lesions
      of intracranial arteries contain relatively less oxidized LDL than similar-size
      lesions of extracranial arteries. Activities of Mn-superoxide dismutase but not
      of Zn-superoxide dismutase, catalase, or glutathione peroxidase were
      significantly higher in both intracranial arteries. CONCLUSIONS: Exposure to
      hypercholesterolemia during fetal development results in extensive formation of
      fatty streaks in extracranial but not intracranial arteries. The fact that such a
      difference in lesion formation occurs in the absence of many other atherogenic
      risk factors found later in life suggests that differences in the atherogenic
      response to hypercholesterolemia are an important contributor to the slower onset
      of the disease in intracranial vessels in adults. Fetal arteries may allow
      elucidation of the mechanisms responsible, for example, better protection of
      intracranial arteries against free radical-mediated atherogenic processes.

PMID- 10209006
TI  - Tracheal aspirate as a substrate for polymerase chain reaction detection of viral
      genome in childhood pneumonia and myocarditis.
AB  - BACKGROUND: Infectious respiratory disorders are important causes of childhood
      morbidity and mortality. Viral causes are common and may lead to rapid
      deterioration, requiring mechanical ventilation; myocardial dysfunction may
      accompany respiratory decompensation. The etiologic viral diagnosis may be
      difficult with classic methods. The purpose of this study was to evaluate
      polymerase chain reaction (PCR) as a diagnostic method for identification of
      causative agents. METHODS AND RESULTS: PCR was used to amplify sequences of
      viruses known to cause childhood viral pneumonia and myocarditis. Oligonucleotide
      primers were designed to amplify specific sequences of DNA virus (adenovirus,
      cytomegalovirus, herpes simplex virus, and Epstein-Barr virus) and RNA virus
      (enterovirus, respiratory syncytial virus, influenza A, and influenza B) genomes.
      Tracheal aspirate samples were obtained from 32 intubated patients and nucleic
      acid extracted before PCR. PCR results were compared with results of culture,
      serology, and antigen detection methods when available. In cases of myocarditis
      (n=7), endomyocardial biopsy samples were analyzed by PCR and compared with
      tracheal aspirate studies. PCR amplification of viral genome occurred in 18 of 32
      samples (56%), with 3 samples PCR positive for 2 viral genomes. Amplified viral
      sequences included RSV (n=3), enterovirus (n=5), cytomegalovirus (n=4),
      adenovirus (n=3), herpes simplex virus (n=2), Epstein-Barr virus (n=1), influenza
      A (n=2), and influenza B (n=1). All 7 cases of myocarditis amplified the same
      viral genome from heart as found by tracheal aspirate. CONCLUSIONS: PCR is a
      rapid and sensitive diagnostic tool in cases of viral pneumonia with or without
      myocarditis, and tracheal aspirate appears to be excellent for analysis.

PMID- 10209007
TI  - Vascular cell apoptosis: cell type-specific modulation by transforming growth
      factor-beta1 in endothelial cells versus smooth muscle cells.
AB  - BACKGROUND: It is postulated that vascular lesion formation and remodeling
      involves a balance between vascular cell death and cell proliferation.
      Transforming growth factor-beta1 (TGF-beta1) is a pleiotropic factor expressed
      within vascular cells that regulates cell growth in a tissue-specific manner.
      This study tested the hypothesis that the control of vascular cell apoptosis
      involves cell type-specific regulation by TGF-beta1. METHODS AND RESULTS: In
      response to serum withdrawal, cultured endothelial cells and vascular smooth
      muscle cells exhibited apoptosis as evidenced by DNA laddering and quantitated by
      analysis of nuclear chromatin morphology. Addition of TGF-beta1 to endothelial
      cells in serum-free media further potentiated the induction of apoptosis in a
      dose-dependent fashion. Moreover, TGF-beta1 promoted endothelial cell death
      despite the presence of 10% serum. However, endothelial cells plated on collagen
      I were resistant to TGF-beta1-induced apoptosis. This antiapoptotic influence of
      the matrix was mimicked by integrin activation with anti-beta1 antibodies and
      associated with increased expression of the antiapoptotic factor bcl-2. In accord
      with the hypothesis that the modulation of antiapoptotic gene expression may
      mediate the effects of TGF-beta1 and beta1 integrins on cell fate, we observed
      that endothelial cells with constitutive upregulation of bcl-2 remained viable
      despite exposure to TGF-beta1 in serum-free conditions. In contrast to the
      proapoptotic effect of TGF-beta1 in endothelial cells, addition of TGF-beta1 to
      vascular smooth muscle cells in serum-free media inhibited apoptosis.
      CONCLUSIONS: These findings suggest that the effect of cytokines such as TGF
      beta1 on cell fate is contextual and is modulated by cell-matrix interactions in
      a cell type-specific manner.

PMID- 10209009
TI  - Angiotensin-converting enzyme inhibitor ramiprilat interferes with the
      sequestration of the B2 kinin receptor within the plasma membrane of native
      endothelial cells.
AB  - BACKGROUND: ACE (kininase II) inhibitors have been shown to exert their
      beneficial cardiovascular effects via the inhibition of both angiotensin II
      formation and bradykinin breakdown. Because recent evidence suggests that ACE
      inhibitors may also interfere with B2 kinin receptor signaling and thus enhance
      the vascular response to bradykinin, we examined whether the distribution of B2
      kinin receptors within the plasma membrane of native endothelial cells is
      affected by an ACE inhibitor. METHODS AND RESULTS: Localization of the B2 kinin
      receptor in membranes prepared from native porcine aortic endothelial cells was
      evaluated by means of specific [3H]bradykinin binding and immunoprecipitation of
      the B2 receptor from isolated membranes. Effects of bradykinin and ramiprilat on
      intracellular signaling were determined by monitoring the activation of the
      extracellularly regulated kinases Erk1 and Erk2 as well as [Ca2+]i increases in
      fura 2-loaded endothelial cells. Stimulation of native endothelial cells with
      bradykinin 100 nmol/L resulted in the time-dependent sequestration of the B2
      receptor to caveolin-rich (CR) membranes, which was maximal after 5 minutes.
      Pretreatment with ramiprilat 100 nmol/L for 15 minutes significantly attenuated
      the recovery of B2 kinin receptors in CR membranes while increasing that from
      membranes lacking caveolin. This effect was not due to the inhibition of
      bradykinin degradation, because no effect was seen in the presence of an
      inhibitory concentration of the synthetic ACE substrate hippuryl-L-histidyl-L
      leucine. Ramiprilat also decreased [3H]bradykinin binding to CR membranes when
      applied either before or after bradykinin stimulation. Moreover, ramiprilat
      resulted in reactivation of the B2 receptor in bradykinin-stimulated cells and
      induced a second peak in [Ca2+]i and reactivation of Erk1/2. CONCLUSIONS: The ACE
      inhibitor ramiprilat interferes with the targeting of the B2 kinin receptor to CR
      membrane domains in native endothelial cells. Therefore, effects other than the
      inhibition of kininase II may account for the effects of ramiprilat and other ACE
      inhibitors on the vascular system.

PMID- 10209010
TI  - Quantification of extracellular and intracellular adenosine production:
      understanding the transmembranous concentration gradient.
AB  - BACKGROUND: Inhibitors of adenosine membrane transport cause vasodilation and
      enhance the plasma adenosine concentration. However, it is unclear why the plasma
      adenosine concentration rises rather than falls when membrane transport is
      inhibited. We tested the hypothesis that the cytosolic adenosine concentration
      exceeds the interstitial concentration under well-oxygenated conditions. METHODS
      AND RESULTS: In isolated, isovolumically working guinea pig hearts (n=50), the
      release rate of adenosine and accumulation of S-adenosylhomocysteine (after 20
      minutes of 200 micromol/L homocysteine), a measure of the free cytosolic
      adenosine concentration, were determined in the absence and presence of specific
      and powerful blockers of adenosine membrane transport (nitrobenzylthioinosine 1
      micromol/L), adenosine deaminase (erythro-9-hydroxy-nonyl-adenine 5 micromol/L),
      and adenosine kinase (iodotubericidine 10 micromol/L). Data analysis with a
      distributed multicompartment model revealed a total cardiac adenosine production
      rate of 2294 pmol. min-1. g-1, of which 8% was produced in the extracellular
      region. Because of a high rate of intracellular metabolism, however, 70.3% of
      extracellularly produced adenosine was taken up into cellular regions, an effect
      that was effectively eliminated by membrane transport block. The resulting
      approximately 2.8-fold increase of the interstitial adenosine concentration
      evoked near-maximal coronary dilation. CONCLUSIONS: We rejected the hypothesis
      that the cytosolic adenosine concentration exceeds the interstitial. Rather,
      there is significant extracellular production, and the parenchymal cell
      represents a sink, not a source, for adenosine under well-oxygenated conditions.

PMID- 10209008
TI  - Increased NADH-oxidase-mediated superoxide production in the early stages of
      atherosclerosis: evidence for involvement of the renin-angiotensin system.
AB  - BACKGROUND: Angiotensin II activates NAD(P)H-dependent oxidases via AT1-receptor
      stimulation, the most important vascular source of superoxide (O2*-). The AT1
      receptor is upregulated in vitro by low-density lipoprotein. The present study
      was designed to test whether hypercholesterolemia is associated with increased
      NAD(P)H-dependent vascular O2*- production and whether AT1-receptor blockade may
      inhibit this oxidase and in parallel improve endothelial dysfunction. METHODS AND
      RESULTS: Vascular responses were determined by isometric tension studies, and
      relative rates of vascular O2*- production were determined by use of
      chemiluminescence with lucigenin, a cypridina luciferin analogue, and electron
      spin resonance studies. AT1-receptor mRNA was quantified by Northern analysis,
      and AT1-receptor density was measured by radioligand binding assays.
      Hypercholesterolemia was associated with impaired endothelium-dependent
      vasodilation and increased O2*- production in intact vessels. In vessel
      homogenates, we found a significant activation of NADH-driven O2*- production in
      both models of hyperlipidemia. Treatment of cholesterol-fed animals with the AT1
      receptor antagonist Bay 10-6734 improved endothelial dysfunction, normalized
      vascular O2*- and NADH-oxidase activity, decreased macrophage infiltration, and
      reduced early plaque formation. In the setting of hypercholesterolemia, the
      aortic AT1 receptor mRNA was upregulated to 166+/-11%, accompanied by a
      comparable increase in AT1-receptor density. CONCLUSIONS: Hypercholesterolemia is
      associated with AT1-receptor upregulation, endothelial dysfunction, and increased
      NADH-dependent vascular O2*- production. The improvement of endothelial
      dysfunction, inhibition of the oxidase, and reduction of early plaque formation
      by an AT1-receptor antagonist suggests a crucial role of angiotensin II-mediated
      O2*- production in the early stage of atherosclerosis.

PMID- 10209011
TI  - Mechanisms of retarded apical filling in acute ischemic left ventricular failure.
AB  - BACKGROUND: We examined the hypothesis that retardation of apical filling as
      measured by color M-mode Doppler echocardiography in the diseased left ventricle
      (LV) reflects a decrease in the intraventricular mitral-to-apical pressure
      gradient. METHODS AND RESULTS: In 9 open-chest anesthetized dogs, micromanometers
      were placed near the mitral tip and in the apical region. From the color M-mode
      Doppler images, the time delay (TD) between peak velocity at the mitral tip and
      the apical region was determined as an index of LV flow propagation. Acute
      ischemic LV failure was induced by coronary microembolization. Induction of
      ischemia caused a marked increase in LV end-diastolic pressure and a decrease in
      LV ejection fraction. The time constant of LV isovolumic apical pressure decay
      (tau) increased from 31+/-8 to 49+/-16 ms (P<0.001). The peak early diastolic
      mitral-to-apical pressure gradient (DeltaPLVmitral-apex) decreased from 1.9+/-0.9
      to 0.7+/-0.5 mm Hg (P<0.01), and TD increased from 5+/-3 to 57+/-26 ms (P<0.001).
      The slowing of flow propagation was limited to the apical portion of the LV
      cavity. The TD correlated with DeltaPLVmitral-apex (r=-0.94, P<0.01) and with tau
      (r=0.92, P<0.01). Before ischemia, the mitral-to-apical flow propagation velocity
      far exceeded the velocity of the individual blood cells, whereas during ischemia,
      flow propagation velocity approximated the blood velocity. CONCLUSIONS:
      Retardation of apical filling in acute ischemic failure was attributed to a
      decrease in the mitral-to-apical driving pressure, reflecting slowing of LV
      relaxation. The slowing of flow propagation appeared to represent a shift in
      apical filling from a pattern of column motion to a pattern dominated by
      convection.

PMID- 10209012
TI  - Trends in antihypertensive drug advertising, 1985-1996.
AB  - BACKGROUND: Over the past decade, calcium channel blockers (CCBs) and ACE
      inhibitors have been used increasingly in the treatment of hypertension. In
      contrast, beta-blocker and diuretic use has decreased. It has been suggested that
      pharmaceutical marketing has influenced these prescribing patterns. No objective
      analysis of advertising for antihypertensive therapies exists, however. METHODS
      AND RESULTS: We reviewed the January, April, July, and October issues of the New
      England Journal of Medicine from 1985 to 1996 (210 issues). The intensity of drug
      promotion was measured as the proportion of advertising pages used to promote a
      given medication. Statistical analyses used the chi2 test for trend. Advertising
      for CCBs increased from 4.6% of advertising pages in 1985 to 26.9% in 1996, while
      advertising for beta-blockers (12.4% in 1985 to 0% in 1996) and diuretics (4.2%
      to 0%) decreased (all P<0.0001). A nonsignificant increase was observed in
      advertising for ACE inhibitors (3.5% to 4.3%, P=0.17). Although the total number
      of drug advertising pages per issue decreased from 60 pages in 1985 to 42 pages
      in 1996 (P<0.001), the number of pages devoted to calcium channel blocker
      advertisements nearly quadrupled. CONCLUSIONS: Increasing promotion of CCBs has
      mirrored trends in physician prescribing. An association between advertising and
      prescribing patterns could explain why CCBs have supplanted better-substantiated
      therapies for hypertension.

PMID- 10209013
TI  - Images in cardiovascular medicine. Demonstration of acute myocardial infarction
      by subsecond spiral computed tomography: early defect and delayed enhancement.

PMID- 10209016
TI  - Case of pulmonary embolism.

PMID- 10209017
TI  - Case of pulmonary embolism 

PMID- 10209019
TI  - Elasticity measurements show the existence of thin rigid cores inside mitotic
      chromosomes.
AB  - Chromosome condensation is one of the most critical steps during cell division.
      However, the structure of condensed mitotic chromosomes is poorly understood. In
      this paper we describe a new approach based on elasticity measurements for
      studying the structure of in vitro assembled mitotic chromosomes in Xenopus egg
      extract. The approach is based on a unique combination of measurements of both
      longitudinal deformability and bending rigidity of whole chromosomes. By using
      specially designed micropipettes, the chromosome force-extension curve was
      determined. Analysis of the curvature fluctuation spectrum allowed for the
      measurement of chromosome bending ridigity. The relationship between the values
      of these two parameters is very specific: the measured chromosome flexibility was
      found to be 2,000 times lower than the flexibility calculated from the
      experimentally determined Young modulus. This requires the chromosome structure
      to be formed of one or a few thin rigid elastic axes surrounded by a soft
      envelope. The properties of these axes are well-described by models developed for
      the elasticity of titin-like molecules. Additionally, the deformability of in
      vitro assembled chromosomes was found to be very similar to that of native
      somatic chromosomes, thus demonstrating the existence of an essentially identical
      structure.

PMID- 10209018
TI  - Uncapping and deregulation of telomeres lead to detrimental cellular consequences
      in yeast.
AB  - Telomeres are the protein-nucleic acid structures at the ends of eukaryote
      chromosomes. Tandem repeats of telomeric DNA are templated by the RNA component
      (TER1) of the ribonucleoprotein telomerase. These repeats are bound by telomere
      binding proteins, which are thought to interact with other factors to create a
      higher-order cap complex that stabilizes the chromosome end. In the budding yeast
      Kluyveromyces lactis, the incorporation of certain mutant DNA sequences into
      telomeres leads to uncapping of telomeres, manifested by dramatic telomere
      elongation and increased length heterogeneity (telomere deregulation). Here we
      show that telomere deregulation leads to enlarged, misshapen "monster" cells with
      increased DNA content and apparent defects in cell division. However, such
      deregulated telomeres became stabilized at their elongated lengths upon addition
      of only a few functionally wild-type telomeric repeats to their ends, after which
      the frequency of monster cells decreased to wild-type levels. These results
      provide evidence for the importance of the most terminal repeats at the telomere
      in maintaining the cap complex essential for normal telomere function. Analysis
      of uncapped and capped telomeres also show that it is the deregulation resulting
      from telomere uncapping, rather than excessive telomere length per se, that is
      associated with DNA aberrations and morphological defects.

PMID- 10209020
TI  - Phosphorylation-induced rearrangement of the histone H3 NH2-terminal domain
      during mitotic chromosome condensation.
AB  - The NH2-terminal domain (N-tail) of histone H3 has been implicated in chromatin
      compaction and its phosphorylation at Ser10 is tightly correlated with mitotic
      chromosome condensation. We have developed one mAb that specifically recognizes
      histone H3 N-tails phosphorylated at Ser10 (H3P Ab) and another that recognizes
      phosphorylated and unphosphorylated H3 N-tails equally well (H3 Ab).
      Immunocytochemistry with the H3P Ab shows that Ser10 phosphorylation begins in
      early prophase, peaks before metaphase, and decreases during anaphase and
      telophase. Unexpectedly, the H3 Ab shows stronger immunofluorescence in mitosis
      than interphase, indicating that the H3 N-tail is more accessible in condensed
      mitotic chromatin than in decondensed interphase chromatin. In vivo ultraviolet
      laser cross-linking indicates that the H3 N-tail is bound to DNA in interphase
      cells and that binding is reduced in mitotic cells. Treatment of mitotic cells
      with the protein kinase inhibitor staurosporine causes histone H3
      dephosphorylation and chromosome decondensation. It also decreases the
      accessibility of the H3 N-tail to H3 Ab and increases the binding of the N-tail
      to DNA. These results indicate that a phosphorylation-dependent weakening of the
      association between the H3 N-tail and DNA plays a role in mitotic chromosome
      condensation.

PMID- 10209021
TI  - RAE1 is a shuttling mRNA export factor that binds to a GLEBS-like NUP98 motif at
      the nuclear pore complex through multiple domains.
AB  - Gle2p is implicated in nuclear export of poly(A)+ RNA and nuclear pore complex
      (NPC) structure and distribution in Saccharomyces cerevisiae. Gle2p is anchored
      at the nuclear envelope (NE) via a short Gle2p-binding motif within Nup116p
      called GLEBS. The molecular mechanism by which Gle2p and the Gle2p-Nup116p
      interaction function in mRNA export is unknown. Here we show that RAE1, the
      mammalian homologue of Gle2p, binds to a GLEBS-like NUP98 motif at the NPC
      through multiple domains that include WD-repeats and a COOH-terminal non-WD
      repeat extension. This interaction is direct, as evidenced by in vitro binding
      studies and chemical cross-linking. Microinjection experiments performed in
      Xenopus laevis oocytes demonstrate that RAE1 shuttles between the nucleus and the
      cytoplasm and is exported from the nucleus in a temperature-dependent and RanGTP
      independent manner. Docking of RAE1 to the NE is highly dependent on new mRNA
      synthesis. Overexpression of the GLEBS-like motif also inhibits NE binding of
      RAE1 and induces nuclear accumulation of poly(A)+ RNA. Both effects are abrogated
      either by the introduction of point mutations in the GLEBS-like motif or by
      overexpression of RAE1, indicating a direct role for RAE1 and the NUP98-RAE1
      interaction in mRNA export. Together, our data suggest that RAE1 is a shuttling
      transport factor that directly contributes to nuclear export of mRNAs through its
      ability to anchor to a specific NUP98 motif at the NPC.

PMID- 10209022
TI  - CRM1-mediated recycling of snurportin 1 to the cytoplasm.
AB  - Importin beta is a major mediator of import into the cell nucleus. Importin beta
      binds cargo molecules either directly or via two types of adapter molecules,
      importin alpha, for import of proteins with a classical nuclear localization
      signal (NLS), or snurportin 1, for import of m3G-capped U snRNPs. Both adapters
      have an NH2-terminal importin beta-binding domain for binding to, and import by,
      importin beta, and both need to be returned to the cytoplasm after having
      delivered their cargoes to the nucleus. We have shown previously that CAS
      mediates export of importin alpha. Here we show that snurportin 1 is exported by
      CRM1, the receptor for leucine-rich nuclear export signals (NESs). However, the
      interaction of CRM1 with snurportin 1 differs from that with previously
      characterized NESs. First, CRM1 binds snurportin 1 50-fold stronger than the Rev
      protein and 5,000-fold stronger than the minimum Rev activation domain. Second,
      snurportin 1 interacts with CRM1 not through a short peptide but rather via a
      large domain that allows regulation of affinity. Strikingly, snurportin 1 has a
      low affinity for CRM1 when bound to its m3G-capped import substrate, and a high
      affinity when substrate-free. This mechanism appears crucial for productive
      import cycles as it can ensure that CRM1 only exports snurportin 1 that has
      already released its import substrate in the nucleus.

PMID- 10209023
TI  - Prefoldin-nascent chain complexes in the folding of cytoskeletal proteins.
AB  - In vitro transcription/translation of actin cDNA and analysis of the translation
      products by native-PAGE was used to study the maturation pathway of actin. During
      the course of actin synthesis, several distinct actin-containing species were
      observed and the composition of each determined by immunological procedures.
      After synthesis of the first approximately 145 amino acids, the nascent ribosome
      associated actin chain binds to the recently identified heteromeric chaperone
      protein, prefoldin (PFD). PFD remains bound to the relatively unfolded actin
      polypeptide until its posttranslational delivery to cytosolic chaperonin (CCT).
      We show that alpha- and beta-tubulin follow a similar maturation pathway, but to
      date find no evidence for an interaction between PFD and several noncytoskeletal
      proteins. We conclude that PFD functions by selectively targeting nascent actin
      and tubulin chains pending their transfer to CCT for final folding and/or
      assembly.

PMID- 10209024
TI  - Overexpression of CALNUC (nucleobindin) increases agonist and thapsigargin
      releasable Ca2+ storage in the Golgi.
AB  - We previously demonstrated that CALNUC, a Ca2+-binding protein with two EF-hands,
      is the major Ca2+-binding protein in the Golgi by 45Ca2+ overlay (Lin, P., H. Le
      Niculescu, R. Hofmeister, J.M. McCaffery, M. Jin, H. Henneman, T. McQuistan, L.
      De Vries, and M. Farquhar. 1998. J. Cell Biol. 141:1515-1527). In this study we
      investigated CALNUC's properties and the Golgi Ca2+ storage pool in vivo. CALNUC
      was found to be a highly abundant Golgi protein (3.8 microg CALNUC/mg Golgi
      protein, 2.5 x 10(5) CALNUC molecules/NRK cell) and to have a single high
      affinity, low capacity Ca2+-binding site (Kd = 6.6 microM, binding capacity = 1.1
      micromol Ca2+/micromol CALNUC). 45Ca2+ storage was increased by 2.5- and 3-fold,
      respectively, in HeLa cells transiently overexpressing CALNUC-GFP and in EcR-CHO
      cells stably overexpressing CALNUC. Deletion of the first EF-hand alpha helix
      from CALNUC completely abolished its Ca2+-binding capability. CALNUC was
      correctly targeted to the Golgi in transfected cells as it colocalized and
      cosedimented with the Golgi marker, alpha-mannosidase II (Man II). Approximately
      70% of the 45Ca2+ taken up by HeLa and CHO cells overexpressing CALNUC was
      released by treatment with thapsigargin, a sarcoplasmic/endoplasmic reticulum
      calcium ATPase (SERCA) (Ca2+ pump) blocker. Stimulation of transfected cells with
      the agonist ATP or IP3 alone (permeabilized cells) also resulted in a significant
      increase in Ca2+ release from Golgi stores. By immunofluorescence, the IP3
      receptor type 1 (IP3R-1) was distributed over the endoplasmic reticulum and
      codistributed with CALNUC in the Golgi. These results provide direct evidence
      that CALNUC binds Ca2+ in vivo and together with SERCA and IP3R is involved in
      establishment of the agonist-mobilizable Golgi Ca2+ store.

PMID- 10209025
TI  - Mgm101p is a novel component of the mitochondrial nucleoid that binds DNA and is
      required for the repair of oxidatively damaged mitochondrial DNA.
AB  - Maintenance of mitochondrial DNA (mtDNA) during cell division is required for
      progeny to be respiratory competent. Maintenance involves the replication,
      repair, assembly, segregation, and partitioning of the mitochondrial nucleoid.
      MGM101 has been identified as a gene essential for mtDNA maintenance in S.
      cerevisiae, but its role is unknown. Using liquid chromatography coupled with
      tandem mass spectrometry, we identified Mgm101p as a component of highly enriched
      nucleoids, suggesting that it plays a nucleoid-specific role in maintenance.
      Subcellular fractionation, indirect immunofluorescence and GFP tagging show that
      Mgm101p is exclusively associated with the mitochondrial nucleoid structure in
      cells. Furthermore, DNA affinity chromatography of nucleoid extracts indicates
      that Mgm101p binds to DNA, suggesting that its nucleoid localization is in part
      due to this activity. Phenotypic analysis of cells containing a temperature
      sensitive mgm101 allele suggests that Mgm101p is not involved in mtDNA packaging,
      segregation, partitioning or required for ongoing mtDNA replication. We examined
      Mgm101p's role in mtDNA repair. As compared with wild-type cells, mgm101 cells
      were more sensitive to mtDNA damage induced by UV irradiation and were
      hypersensitive to mtDNA damage induced by gamma rays and H2O2 treatment. Thus, we
      propose that Mgm101p performs an essential function in the repair of oxidatively
      damaged mtDNA that is required for the maintenance of the mitochondrial genome.

PMID- 10209026
TI  - An essential role for katanin in severing microtubules in the neuron.
AB  - Several lines of evidence suggest that microtubules are nucleated at the neuronal
      centrosome, and then released for transport into axons and dendrites. Here we
      sought to determine whether the microtubule-severing protein known as katanin
      mediates microtubule release from the neuronal centrosome. Immunomicroscopic
      analyses on cultured sympathetic neurons show that katanin is present at the
      centrosome, but is also widely distributed throughout the neuron. Microinjection
      of an antibody that inactivates katanin results in a dramatic accumulation of
      microtubules at the centrosome, indicating that katanin is indeed required for
      microtubule release from the centrosome. However, the antibody also causes an
      inhibition of axon outgrowth that is more immediate than expected on this basis
      alone. It may be that katanin severs microtubules throughout the cell body to
      keep them sufficiently short to be efficiently transported into developing
      processes. Consistent with this idea, there were significantly fewer free ends of
      microtubules in the cell bodies of neurons that had been injected with the
      katanin antibody compared with controls. These results indicate that microtubule
      severing by katanin is essential for releasing microtubules from the neuronal
      centrosome, and also for regulating the length of the microtubules after their
      release.

PMID- 10209027
TI  - Rac homologues and compartmentalized phosphatidylinositol 4, 5-bisphosphate act
      in a common pathway to regulate polar pollen tube growth.
AB  - Pollen tube cells elongate based on actin- dependent targeted secretion at the
      tip. Rho family small GTPases have been implicated in the regulation of related
      processes in animal and yeast cells. We have functionally characterized Rac type
      Rho family proteins that are expressed in growing pollen tubes. Expression of
      dominant negative Rac inhibited pollen tube elongation, whereas expression of
      constitutive active Rac induced depolarized growth. Pollen tube Rac was found to
      accumulate at the tip plasma membrane and to physically associate with a
      phosphatidylinositol monophosphate kinase (PtdIns P-K) activity.
      Phosphatidylinositol 4, 5-bisphosphate (PtdIns 4, 5-P2), the product of PtdIns P
      Ks, showed a similar intracellular localization as Rac. Expression of the
      pleckstrin homology (PH)-domain of phospholipase C (PLC)-delta1, which binds
      specifically to PtdIns 4, 5-P2, inhibited pollen tube elongation. These results
      indicate that Rac and PtdIns 4, 5-P2 act in a common pathway to control polar
      pollen tube growth and provide direct evidence for a function of PtdIns 4, 5-P2
      compartmentalization in the regulation of this process.

PMID- 10209028
TI  - Relationship between Arp2/3 complex and the barbed ends of actin filaments at the
      leading edge of carcinoma cells after epidermal growth factor stimulation.
AB  - Using both light and high resolution electron microscopy, we analyzed the spatial
      and temporal relationships between the Arp2/3 complex and the nucleation activity
      that is required for lamellipod extension in mammary carcinoma cells after
      epidermal growth factor stimulation. A rapid two- to fourfold increase in
      filament barbed end number occurs transiently after stimulation and remains
      confined almost exclusively to the extreme outer edge of the extending lamellipod
      (within 100-200 nm of the plasma membrane). This is accompanied by an increase in
      filament density at the leading edge and a general decrease in filament length,
      with a specific loss of long filaments. Concomitantly, the Arp2/3 complex is
      recruited with a 1.5-fold increase throughout the entire cortical filament
      network extending 1-1.5 microm in depth from the membrane at the leading edge.
      The recruitment of the Arp2/3 complex at the membrane of the extending lamellipod
      indicates that Arp2/3 may be involved in initial generation of growing filaments.
      However, only a small subset of the complex present in the cortical network
      colocalizes near free barbed ends. This suggests that the 100-200-nm
      submembraneous compartment at the leading edge of the extending lamellipod
      constitutes a special biochemical microenvironment that favors the generation and
      maintenance of free barbed ends, possibly through the locally active Arp2/3
      complex, severing or decreasing the on-rate of capping protein. Our results are
      inconsistent with the hypothesis suggesting uncapping is the dominant mechanism
      responsible for the generation of nucleation activity. However, they support the
      hypothesis of an Arp2/3-mediated capture of actin oligomers that formed close to
      the membrane by other mechanisms such as severing. They also support pointed-end
      capping by the Arp2/3 complex, accounting for its wide distribution at the
      leading edge.

PMID- 10209029
TI  - Phosphorylation of adducin by Rho-kinase plays a crucial role in cell motility.
AB  - Adducin is a membrane skeletal protein that binds to actin filaments (F-actin)
      and thereby promotes the association of spectrin with F-actin to form a spectrin
      actin meshwork beneath plasma membranes such as ruffling membranes. Rho
      associated kinase (Rho- kinase), which is activated by the small guanosine
      triphosphatase Rho, phosphorylates alpha-adducin and thereby enhances the F-actin
      binding activity of alpha-adducin in vitro. Here we identified the sites of
      phosphorylation of alpha-adducin by Rho-kinase as Thr445 and Thr480. We prepared
      antibody that specifically recognized alpha-adducin phosphorylated at Thr445, and
      found by use of this antibody that Rho-kinase phosphorylated alpha-adducin at
      Thr445 in COS7 cells in a Rho-dependent manner. Phosphorylated alpha-adducin
      accumulated in the membrane ruffling area of Madin-Darby canine kidney (MDCK)
      epithelial cells and the leading edge of scattering cells during the action of
      tetradecanoylphorbol-13-acetate (TPA) or hepatocyte growth factor (HGF). The
      microinjection of Botulinum C3 ADP-ribosyl-transferase, dominant negative Rho
      kinase, or alpha-adducinT445A,T480A (substitution of Thr445 and Thr480 by Ala)
      inhibited the TPA-induced membrane ruffling in MDCK cells and wound-induced
      migration in NRK49F cells. alpha-AdducinT445D,T480D (substitution of Thr445 and
      Thr480 by Asp), but not alpha-adducinT445A,T480A, counteracted the inhibitory
      effect of the dominant negative Rho-kinase on the TPA-induced membrane ruffling
      in MDCK cells. Taken together, these results indicate that Rho-kinase
      phosphorylates alpha-adducin downstream of Rho in vivo, and that the
      phosphorylation of adducin by Rho-kinase plays a crucial role in the regulation
      of membrane ruffling and cell motility.

PMID- 10209030
TI  - Cellular uptake of chloroquine is dependent on binding to ferriprotoporphyrin IX
      and is independent of NHE activity in Plasmodium falciparum.
AB  - Here we provide definitive evidence that chloroquine (CQ) uptake in Plasmodium
      falciparum is determined by binding to ferriprotoporphyrin IX (FPIX). Specific
      proteinase inhibitors that block the degradation of hemoglobin and stop the
      generation of FPIX also inhibit CQ uptake. Food vacuole enzymes can generate cell
      free binding, using human hemoglobin as a substrate. This binding accounts for CQ
      uptake into intact cells and is subject to identical inhibitor specificity.
      Inhibition of CQ uptake by amiloride derivatives occurs because of inhibition of
      CQ-FPIX binding rather than inhibition of the Na+/H+ exchanger (NHE). Inhibition
      of parasite NHE using a sodium-free medium does not inhibit CQ uptake nor does it
      alter the ability of amilorides to inhibit uptake. CQ resistance is characterized
      by a reduced affinity of CQ-FPIX binding that is reversible by verapamil. Diverse
      compounds that are known to disrupt lysosomal pH can mimic the verapamil effect.
      These effects are seen in sodium-free medium and are not due to stimulation of
      the NHE. We propose that these compounds increase CQ accumulation and overcome CQ
      resistance by increasing the pH of lysosomes and endosomes, thereby causing an
      increased affinity of binding of CQ to FPIX.

PMID- 10209031
TI  - Dual fatty acylation of p59(Fyn) is required for association with the T cell
      receptor zeta chain through phosphotyrosine-Src homology domain-2 interactions.
AB  - The first 10 residues within the Src homology domain (SH)-4 domain of the Src
      family kinase Fyn are required for binding to the immune receptor tyrosine-based
      activation motif (ITAM) of T cell receptor (TCR) subunits. Recently, mutation of
      glycine 2, cysteine 3, and lysines 7 and 9 was shown to block binding of Fyn to
      TCR zeta chain ITAMs, prompting the designation of these residues as an ITAM
      recognition motif (Gauen, L.K.T., M.E. Linder, and A.S. Shaw. 1996. J. Cell Biol.
      133:1007-1015). Here we show that these residues do not mediate direct
      interactions with TCR ITAMs, but rather are required for efficient myristoylation
      and palmitoylation of Fyn. Specifically, coexpression of a K7,9A-Fyn mutant with
      N-myristoyltransferase restored myristoylation, membrane binding, and association
      with the cytoplasmic tail of TCR zeta fused to CD8. Conversely, treatment of
      cells with 2-hydroxymyristate, a myristoylation inhibitor, blocked association of
      wild-type Fyn with zeta. The Fyn NH2 terminus was necessary but not sufficient
      for interaction with zeta and both Fyn kinase and SH2 domains were required,
      directing phosphorylation of zeta ITAM tyrosines and binding to zeta ITAM
      phosphotyrosines. Fyn/zeta interaction was sensitive to octylglucoside and
      filipin, agents that disrupt membrane rafts. Moreover, a plasma membrane bound,
      farnesylated Fyn construct, G2A,C3S-FynKRas, was not enriched in the detergent
      insoluble fraction and did not associate with zeta. We conclude that the Fyn SH4
      domain provides the signals for fatty acylation and specific plasma membrane
      localization, stabilizing the interactions between the Fyn SH2 domain and
      phosphotyrosines in TCR zeta chain ITAMs.

PMID- 10209032
TI  - A PDZ-containing scaffold related to the dystrophin complex at the basolateral
      membrane of epithelial cells.
AB  - Membrane scaffolding complexes are key features of many cell types, serving as
      specialized links between the extracellular matrix and the actin cytoskeleton. An
      important scaffold in skeletal muscle is the dystrophin-associated protein
      complex. One of the proteins bound directly to dystrophin is syntrophin, a
      modular protein comprised entirely of interaction motifs, including PDZ (protein
      domain named for PSD-95, discs large, ZO-1) and pleckstrin homology (PH) domains.
      In skeletal muscle, the syntrophin PDZ domain recruits sodium channels and
      signaling molecules, such as neuronal nitric oxide synthase, to the dystrophin
      complex. In epithelia, we identified a variation of the dystrophin complex, in
      which syntrophin, and the dystrophin homologues, utrophin and dystrobrevin, are
      restricted to the basolateral membrane. We used exogenously expressed green
      fluorescent protein (GFP)-tagged fusion proteins to determine which domains of
      syntrophin are responsible for its polarized localization. GFP-tagged full-length
      syntrophin targeted to the basolateral membrane, but individual domains remained
      in the cytoplasm. In contrast, the second PH domain tandemly linked to a highly
      conserved, COOH-terminal region was sufficient for basolateral membrane targeting
      and association with utrophin. The results suggest an interaction between
      syntrophin and utrophin that leaves the PDZ domain of syntrophin available to
      recruit additional proteins to the epithelial basolateral membrane. The assembly
      of multiprotein signaling complexes at sites of membrane specialization may be a
      widespread function of dystrophin-related protein complexes.

PMID- 10209034
TI  - The integrin alpha9beta1 mediates adhesion to activated endothelial cells and
      transendothelial neutrophil migration through interaction with vascular cell
      adhesion molecule-1.
AB  - The integrin alpha9beta1 has been shown to be widely expressed on smooth muscle
      and epithelial cells, and to mediate adhesion to the extracellular matrix
      proteins osteopontin and tenascin-C. We have found that the peptide sequence this
      integrin recognizes in tenascin-C is highly homologous to the sequence recognized
      by the closely related integrin alpha4beta1, in the inducible endothelial ligand,
      vascular cell adhesion mole-cule-1 (VCAM-1). We therefore sought to determine
      whether alpha9beta1 also recognizes VCAM-1, and whether any such interaction
      would be biologically significant. In this report, we demonstrate that
      alpha9beta1 mediates stable cell adhesion to recombinant VCAM-1 and to VCAM-1
      induced on human umbilical vein endothelial cells by tumor necrosis factor-alpha.
      Furthermore, we show that alpha9beta1 is highly and selectively expressed on
      neutrophils and is critical for neutrophil migration on VCAM-1 and tenascin-C.
      Finally, alpha9beta1 and alpha4 integrins contribute to neutrophil chemotaxis
      across activated endothelial monolayers. These observations suggest a possible
      role for alpha9beta1/VCAM-1 interactions in extravasation of neutrophils at sites
      of acute inflammation.

PMID- 10209033
TI  - Visualization of chemokine binding sites on human brain microvessels.
AB  - The chemokines monocyte chemoattractant protein-1 (MCP-1) and macrophage
      inflammatory protein-1alpha (MIP-1alpha) aid in directing leukocytes to specific
      locales within the brain and spinal cord during central nervous system
      inflammation. However, it remains unclear how these chemokines exert their
      actions across a vascular barrier, raising speculation that interaction with
      endothelial cells might be required. Therefore, experiments were performed to
      determine whether binding domains for these chemokines exist along the outer
      surface of brain microvessels, a feature that could potentially relay chemokine
      signals from brain to blood. Using a biotinylated chemokine binding assay with
      confocal microscopy and three-dimensional image reconstruction, spatially
      resolved binding sites for MCP-1 and MIP-alpha around human brain microvessels
      were revealed for the first time. Binding of labeled MCP-1 and MIP-1alpha could
      be inhibited by unlabeled homologous but not heterologous chemokine, and was
      independent of the presence of heparan sulfate, laminin, or collagen in the
      subendothelial matrix. This is the first evidence of specific and separate
      binding domains for MCP-1 and MIP-1alpha on the parenchymal surface of
      microvessels, and highlights the prospect that specific interactions of
      chemokines with microvascular elements influence the extent and course of central
      nervous system inflammation.

PMID- 10209035
TI  - Hapten-induced colitis is associated with colonic patch hypertrophy and T helper
      cell 2-type responses.
AB  - To investigate the potential involvement of T helper (Th)2-type responses in
      murine models of intestinal inflammation, we used trinitrobenzene sulfonic acid
      (TNBS)-hapten to induce inflammatory bowel disease in situations where Th1-type
      responses with interferon (IFN)-gamma synthesis are either diminished or do not
      occur. Intracolonic administration of TNBS to either normal (IFN-gamma+/+) or Th1
      deficient IFN-gamma knockout (IFN-gamma-/-) BALB/c mice resulted in significant
      colitis. In IFN-gamma-/- mice, crypt inflammation was more severe than in IFN
      gamma+/+ mice and was accompanied by hypertrophy of colonic patches with a
      lymphoepithelium containing M cells and distinct B and T cell zones resembling
      Peyer's patches. Hapten-specific, colonic patch T cells from both mouse groups
      exhibited a Th2 phenotype with interleukin (IL)-4 and IL-5 production. TNBS
      colitis in normal mice treated with anti-IL-4 antibodies or in IL-4(-/-) mice was
      less severe than in either IFN-gamma+/+ or IFN-gamma-/- mice. Our findings now
      show that the Th2-type responses in TNBS colitis are associated with colonic
      patch enlargement and inflammation of the mucosal layer and may represent a model
      for ulcerative colitis.

PMID- 10209037
TI  - Dual role for Fas ligand in the initiation of and recovery from experimental
      allergic encephalomyelitis.
AB  - We have previously demonstrated a role for Fas and Fas ligand (FasL) in the
      pathogenesis of experimental allergic encephalomyelitis (EAE). However, using an
      active induction paradigm we could not distinguish between FasL expressed on
      activated CD4(+) T cells from that expressed on other inflammatory or resident
      central nervous system (CNS) cells. To address this issue, we have conducted
      reciprocal adoptive transfer experiments of nontransgenic or myelin basic protein
      specific T cell receptor transgenic wild-type, lpr, or gld lymphocytes into
      congenic wild-type, lpr, and gld hosts. We found that FasL expressed on donor
      cells is important for the development of EAE, as FasL-deficient lymphocytes
      transfer attenuated disease. Furthermore, Fas expressed in the recipient animals
      is important for the progression of EAE, as clinical signs of disease in lpr
      recipients were dramatically attenuated after transfer of either wild-type or lpr
      T cells. Surprisingly, these experiments also identified CNS cells as a source of
      functional FasL. Host-derived FasL appears to be especially important in the
      recovery from EAE, as many gld recipients of wild-type lymphocytes develop
      prolonged clinical signs of disease. Thus it appears that FasL plays distinct
      roles in EAE during the initiation of and recovery from disease.

PMID- 10209036
TI  - SHP2-interacting transmembrane adaptor protein (SIT), a novel disulfide-linked
      dimer regulating human T cell activation.
AB  - T lymphocytes express several low molecular weight transmembrane adaptor proteins
      that recruit src homology (SH)2 domain-containing intracellular molecules to the
      cell membrane via tyrosine-based signaling motifs. We describe here a novel
      molecule of this group termed SIT (SHP2 interacting transmembrane adaptor
      protein). SIT is a disulfide-linked homodimeric glycoprotein that is expressed in
      lymphocytes. After tyrosine phosphorylation by src and possibly syk protein
      tyrosine kinases SIT recruits the SH2 domain-containing tyrosine phosphatase SHP2
      via an immunoreceptor tyrosine-based inhibition motif. Overexpression of SIT in
      Jurkat cells downmodulates T cell receptor- and phytohemagglutinin-mediated
      activation of the nuclear factor of activated T cells (NF-AT) by interfering with
      signaling processes that are probably located upstream of activation of
      phospholipase C. However, binding of SHP2 to SIT is not required for inhibition
      of NF-AT induction, suggesting that SIT not only regulates NF-AT activity but
      also controls NF-AT unrelated pathways of T cell activation involving SHP2.

PMID- 10209038
TI  - Targeted gene disruption reveals an adhesin indispensable for pathogenicity of
      Blastomyces dermatitidis.
AB  - Systemic fungal infections are becoming more common and difficult to treat, yet
      the pathogenesis of these infectious diseases remains poorly understood. In many
      cases, pathogenicity can be attributed to the ability of the fungi to adhere to
      target tissues, but the lack of tractable genetic systems has limited progress in
      understanding and interfering with the offending fungal products. In Blastomyces
      dermatitidis, the agent of blastomycosis, a respiratory and disseminated mycosis
      of people and animals worldwide, expression of the putative adhesin encoded by
      the WI-1 gene was investigated as a possible virulence factor. DNA-mediated gene
      transfer was used to disrupt the WI-1 locus by allelic replacement, resulting in
      impaired binding and entry of yeasts into macrophages, loss of adherence to lung
      tissue, and abolishment of virulence in mice; each of these properties was fully
      restored after reconstitution of WI-1 by means of gene transfer. These findings
      establish the pivotal role of WI-1 in adherence and virulence of B. dermatitidis
      yeasts. To our knowledge, they offer the first example of a genetically proven
      virulence determinant among systemic dimorphic fungi, and underscore the value of
      reverse genetics for studies of pathogenesis in these organisms.

PMID- 10209039
TI  - Presentation of antigen in immune complexes is boosted by soluble bacterial
      immunoglobulin binding proteins.
AB  - Using a snake toxin as a proteic antigen (Ag), two murine toxin-specific
      monoclonal antibodies (mAbs), splenocytes, and two murine Ag-specific T cell
      hybridomas, we showed that soluble protein A (SpA) from Staphylococcus aureus and
      protein G from Streptococcus subspecies, two Ig binding proteins (IBPs), not only
      abolish the capacity of the mAbs to decrease Ag presentation but also increase Ag
      presentation 20-100-fold. Five lines of evidence suggest that this phenomenon
      results from binding of an IBP-Ab-Ag complex to B cells possessing IBP receptors.
      First, we showed that SpA is likely to boost presentation of a free mAb,
      suggesting that the IBP-boosted presentation of an Ag in an immune complex
      results from the binding of IBP to the mAb. Second, FACS analyses showed that an
      Ag-Ab complex is preferentially targeted by SpA to a subpopulation of splenocytes
      mainly composed of B cells. Third, SpA-dependent boosted presentation of an Ag-Ab
      complex is further enhanced when splenocytes are enriched in cells containing SpA
      receptors. Fourth, the boosting effect largely diminishes when splenocytes are
      depleted of cells containing SpA receptors. Fifth, the boosting effect occurs
      only when IBP simultaneously contains a Fab and an Fc binding site. Altogether,
      our data suggest that soluble IBPs can bridge immune complexes to APCs containing
      IBP receptors, raising the possibility that during an infection process by
      bacteria secreting these IBPs, Ag-specific T cells may activate IBP receptor
      containing B cells by a mechanism of intermolecular help, thus leading to a
      nonspecific immune response.

PMID- 10209040
TI  - Signal transducer and activator of transcription (STAT)5 activation by BCR/ABL is
      dependent on intact Src homology (SH)3 and SH2 domains of BCR/ABL and is required
      for leukemogenesis.
AB  - Signal transducer and activator of transcription (STAT)5 is constitutively
      activated in BCR/ ABL-expressing cells, but the mechanisms and functional
      consequences of such activation are unknown. We show here that BCR/ABL induces
      phosphorylation and activation of STAT5 by a mechanism that requires the BCR/ABL
      Src homology (SH)2 domain and the proline-rich binding site of the SH3 domain.
      Upon expression in 32Dcl3 growth factor-dependent myeloid precursor cells, STAT5
      activation-deficient BCR/ABL SH3+SH2 domain mutants functioned as tyrosine kinase
      and activated Ras, but failed to protect from apoptosis induced by withdrawal of
      interleukin 3 and/or serum and did not induce leukemia in severe combined
      immunodeficiency mice. In complementation assays, expression of a dominant-active
      STAT5B mutant (STAT5B-DAM), but not wild-type STAT5B (STAT5B-WT), in 32Dcl3 cells
      transfected with STAT5 activation-deficient BCR/ABL SH3+SH2 mutants restored
      protection from apoptosis, stimulated growth factor-independent cell cycle
      progression, and rescued the leukemogenic potential in mice. Moreover, expression
      of a dominant-negative STAT5B mutant (STAT5B-DNM) in 32Dcl3 cells transfected
      with wild-type BCR/ABL inhibited apoptosis resistance, growth factor-independent
      proliferation, and the leukemogenic potential of these cells. In retrovirally
      infected mouse bone marrow cells, expression of STAT5B-DNM inhibited BCR/ABL
      dependent transformation. Moreover, STAT5B-DAM, but not STAT5B-WT, markedly
      enhanced the ability of STAT5 activation-defective BCR/ABL SH3+SH2 mutants to
      induce growth factor-independent colony formation of primary mouse bone marrow
      progenitor cells. However, STAT5B-DAM did not rescue the growth factor
      independent colony formation of kinase-deficient K1172R BCR/ABL or the triple
      mutant Y177F+R522L+ Y793F BCR/ABL, both of which also fail to activate STAT5.
      Together, these data demonstrate that STAT5 activation by BCR/ABL is dependent on
      signaling from more than one domain and document the important role of STAT5
      regulated pathways in BCR/ABL leukemogenesis.

PMID- 10209041
TI  - GrpL, a Grb2-related adaptor protein, interacts with SLP-76 to regulate nuclear
      factor of activated T cell activation.
AB  - Propagation of signals from the T cell antigen receptor (TCR) involves a number
      of adaptor molecules. SH2 domain-containing protein 76 (SLP-76) interacts with
      the guanine nucleotide exchange factor Vav to activate the nuclear factor of
      activated cells (NF-AT), and its expression is required for normal T cell
      development. We report the cloning and characterization of a novel Grb2-like
      adaptor molecule designated as Grb2-related protein of the lymphoid system
      (GrpL). Expression of GrpL is restricted to hematopoietic tissues, and it is
      distinguished from Grb2 by having a proline-rich region. GrpL can be
      coimmunoprecipitated with SLP-76 but not with Sos1 or Sos2 from Jurkat cell
      lysates. In contrast, Grb2 can be coimmunoprecipitated with Sos1 and Sos2 but not
      with SLP-76. Moreover, tyrosine-phosphorylated LAT/pp36/38 in detergent lysates
      prepared from anti-CD3 stimulated T cells associated with Grb2 but not GrpL.
      These data reveal the presence of distinct complexes involving GrpL and Grb2 in T
      cells. A functional role of the GrpL-SLP-76 complex is suggested by the ability
      of GrpL to act alone or in concert with SLP-76 to augment NF-AT activation in
      Jurkat T cells.

PMID- 10209042
TI  - Increased adhesion and aggregation of platelets lacking cyclic guanosine 3',5'
      monophosphate kinase I.
AB  - Atherosclerotic vascular lesions are considered to be a major cause of ischemic
      diseases, including myocardial infarction and stroke. Platelet adhesion and
      aggregation during ischemia-reperfusion are thought to be the initial steps
      leading to remodeling and reocclusion of the postischemic vasculature. Nitric
      oxide (NO) inhibits platelet aggregation and smooth muscle proliferation. A major
      downstream target of NO is cyclic guanosine 3', 5'-monophosphate kinase I (cGKI).
      To test the intravascular significance of the NO/cGKI signaling pathway in vivo,
      we have studied platelet-endothelial cell and platelet-platelet interactions
      during ischemia/reperfusion using cGKI-deficient (cGKI-/-) mice. Platelet cGKI
      but not endothelial or smooth muscle cGKI is essential to prevent intravascular
      adhesion and aggregation of platelets after ischemia. The defect in platelet cGKI
      is not compensated by the cAMP/cAMP kinase pathway supporting the essential role
      of cGKI in prevention of ischemia-induced platelet adhesion and aggregation.

PMID- 10209043
TI  - The transmembrane sequence of human histocompatibility leukocyte antigen (HLA)-C
      as a determinant in inhibition of a subset of natural killer cells.
AB  - Molecular interactions with the extracellular domains of class I major
      histocompatibility complex proteins are major determinants of immune recognition
      that have been extensively studied both physically and biochemically. However, no
      immunological function has yet been placed on the transmembrane or cytoplasmic
      amino acid sequences of these proteins despite strict conservation of unique
      features within each class I major histocompatibility complex locus. Here we
      report that lysis by a subset of natural killer (NK) cells inhibited by target
      cell expression of human histocompatibility leukocyte antigen (HLA)-Cw6 or -Cw7
      was not inhibited by expression of chimeric proteins consisting of the
      extracellular domains of HLA-C and the COOH-terminal portion of HLA-G. Assays
      using transfectants expressing a variety of HLA-Cw6 mutants identified the
      transmembrane sequence and, in particular, cysteine at position 309 as necessary
      for inhibition of 68% (25/37) of NK cell lines and 23% (33/145) of NK clones
      tested. Moreover, these NK clones inhibited by target cell expression of HLA-Cw6
      and dependent upon the transmembrane sequence were found not to express or to
      only dimly express NK inhibitory receptors (NKIR1) that are EB6/HP3E4-positive.
      Furthermore, assays using monoclonal antibody blocking suggest that an NK
      receptor other than NKIR1 or CD94 is responsible for recognition dependent upon
      the transmembrane sequence of HLA-Cw6.

PMID- 10209044
TI  - Microbial epitopes act as altered peptide ligands to prevent experimental
      autoimmune encephalomyelitis.
AB  - Molecular mimicry refers to structural homologies between a self-protein and a
      microbial protein. A major epitope of myelin basic protein (MBP), p87-99
      (VHFFKNIVTPRTP), induces experimental autoimmune encephalomyelitis (EAE). VHFFK
      contains the major residues for binding of this self-molecule to T cell receptor
      (TCR) and to the major histocompatibility complex. Peptides from papilloma virus
      strains containing the motif VHFFK induce EAE. A peptide from human papilloma
      virus type 40 (HPV 40) containing VHFFR, and one from HPV 32 containing VHFFH,
      prevented EAE. A sequence from Bacillus subtilis (RKVVTDFFKNIPQRI) also prevented
      EAE. T cell lines, producing IL-4 and specific for these microbial peptides,
      suppressed EAE. Thus, microbial peptides, differing from the core motif of the
      self-antigen, MBPp87-99, function as altered peptide ligands, and behave as TCR
      antagonists, in the modulation of autoimmune disease.

PMID- 10209045
TI  - A critical role for Fas ligand in the active suppression of systemic immune
      responses by ultraviolet radiation.
AB  - Induction of antigen-specific suppression elicited by environmental insults, such
      as ultraviolet (UV)-B radiation in sunlight, can inhibit an effective immune
      response in vivo and may contribute to the outgrowth of UV-induced skin cancer.
      Although UV-induced DNA damage is known to be an initiating event in the immune
      suppression of most antigen responses, the underlying mechanism(s) of such
      suppression remain undefined. In this report, we document that Fas ligand (FasL)
      is critical for UV-induced systemic immune suppression. Normal mice acutely
      exposed to UV exhibit a profound suppression of both contact hypersensitivity and
      delayed type hypersensitivity (DTH) reactions and the development of transferable
      antigen-specific suppressor cells. FasL-deficient mice exposed to UV lack both
      transferable suppressor cell activity and primary suppression to all antigens
      tested, with the exception of the DTH response to allogeneic spleen cells.
      Interestingly, suppression of this response is also known to occur independently
      of UV-induced DNA damage. Delivery of alloantigen as protein, rather than intact
      cells, restored the requirement for FasL in UV-induced immune suppression of this
      response. These results substantiate that FasL/Fas interactions are essential for
      systemic UV-induced suppression of immune responses that involve host antigen
      presentation and suggest an interrelationship between UV-induced DNA damage and
      FasL in this phenomenon. Collectively, our results suggest a model whereby UV
      induced DNA damage disarms the immune system in a manner similar to that observed
      in immunologically privileged sites.

PMID- 10209046
TI  - Extended duration of DH-JH rearrangement in immunoglobulin heavy chain transgenic
      mice: implications for regulation of allelic exclusion.
AB  - Here we show that suppression of VH-DJH rearrangement in mice bearing a mu heavy
      (H) chain transgene (mu-tg mice) is associated with an extended period of DH-JH
      rearrangement, the first step of Immunoglobulin H chain gene rearrangement.
      Whereas DH-JH rearrangement is normally initiated and completed at the pro-B cell
      stage, in mu-tg mice it continues beyond this stage and occurs most frequently at
      the small (late) pre-B stage. Despite ongoing DH-JH rearrangement in late pre-B
      cells of mu-tg mice, VH-DJH rearrangement is not detectable in these cells. We
      infer that the lack of VH-DJH rearrangement primarily reflects tg-induced
      acceleration of B cell differentiation past the stage at which rearrangement of
      VH elements is permissible. In support of this inference, we find that the normal
      representation of early B lineage subsets is markedly altered in mu-tg mice. We
      suggest that the effect of a productive VH-DJH rearrangement at an endogenous H
      chain allele may be similar to that of a mu-tg; i.e., cells that make a
      productive VH-DJH rearrangement on the first attempt rapidly progress to a
      developmental stage that precludes VH-DJH rearrangement at the other allele
      (allelic exclusion).

PMID- 10209047
TI  - Deficiency in CD22, a B cell-specific inhibitory receptor, is sufficient to
      predispose to development of high affinity autoantibodies.
AB  - CD22 is a B cell-specific transmembrane glycoprotein that acts to dampen signals
      generated through the B cell antigen receptor (BCR): B cells from CD22-deficient
      mice give increased Ca2+ fluxes on BCR ligation. Here we show that this B cell
      hyperresponsiveness correlates with the development of autoantibodies. After the
      age of eight months, CD22-deficient mice developed high titers of serum IgG
      directed against double-stranded DNA; these antibodies were of multiclonal
      origin, somatically mutated, and high affinity. Increased titers of antibodies to
      cardiolipin and myeloperoxidase were also noted. The results demonstrate that a
      single gene defect exclusive to B lymphocytes is, without additional contrivance,
      sufficient to trigger autoantibody development in a large proportion of aging
      animals. Thus, CD22 might have evolved specifically to regulate B cell triggering
      thresholds for the avoidance of autoimmunity.

PMID- 10209048
TI  - Two roads diverged: interferon alpha/beta- and interleukin 12-mediated pathways
      in promoting T cell interferon gamma responses during viral infection.
AB  - Viral infections induce CD8 T cell expansion and interferon (IFN)-gamma
      production for defense, but the innate cytokines shaping these responses have not
      been identified. Although interleukin (IL)-12 has the potential to contribute, IL
      12-dependent T cell IFN-gamma has not been detected during viral infections.
      Moreover, certain viruses fail to induce IL-12, and elicit high levels of IFN
      alpha/beta to negatively regulate it. The endogenous factors promoting virus
      induced T cell IFN-gamma production were defined in studies evaluating CD8 T cell
      responses during lymphocytic choriomeningitis virus infections of mice. Two
      divergent supporting pathways were characterized. Under normal conditions of
      infections, the CD8 T cell IFN-gamma response was dependent on endogenous IFN
      alpha/beta effects, but was IL-12 independent. In contrast, in the absence of IFN
      alpha/beta functions, an IL-12 response was revealed and substituted an
      alternative pathway to IFN-gamma. IFN-alpha/beta-mediated effects resulted in
      enhanced, but the alternative pathway also promoted, resistance to infection.
      These observations define uniquely important IFN-alpha/beta-controlled pathways
      shaping T cell responses during viral infections, and demonstrate plasticity of
      immune responses in accessing divergent innate mechanisms to achieve similar
      ultimate goals.

PMID- 10209049
TI  - The effect of graft-versus-host disease on T cell production and homeostasis.
AB  - The aim of this work was to decipher how graft-versus-host disease (GVHD) affects
      T cell production and homeostasis. In GVHD+ mice, thymic output was decreased
      fourfold relative to normal mice, but was sufficient to maintain a T cell
      repertoire with normal diversity in terms of Vbeta usage. Lymphoid hypoplasia in
      GVHD+ mice was caused mainly by a lessened expansion of the peripheral postthymic
      T cell compartment. In 5-bromo-2'-deoxyuridine pulse-chase experiments, resident
      T cells in the spleen of GVHD+ mice showed a normal turnover rate (proliferation
      and half-life). When transferred into thymectomized GVHD- secondary hosts, T
      cells from GVHD+ mice expanded normally. In contrast, normal T cells failed to
      expand when injected into GVHD+ mice. Thus, the reduced size of the postthymic
      compartment in GVHD+ mice was not due to an intrinsic lymphocyte defect, but to
      an extrinsic microenvironment abnormality. We suggest that this extrinsic anomaly
      is consistent with a reduced number of functional peripheral T cell niches.
      Therefore, our results show that GVHD-associated T cell hypoplasia is largely
      caused by a perturbed homeostasis of the peripheral compartment. Furthermore,
      they suggest that damage to the microenvironment of secondary lymphoid organs may
      represent an heretofore unrecognized cause of acquired T cell hypoplasia.

PMID- 10209052
TI  - [Spanish microbiologists in the last 60 years].

PMID- 10209050
TI  - Monocyte-mediated tumoricidal activity via the tumor necrosis factor-related
      cytokine, TRAIL.
AB  - TRAIL (tumor necrosis factor [TNF]-related apoptosis-inducing ligand) is a
      molecule that displays potent antitumor activity against selected targets. The
      results presented here demonstrate that human monocytes rapidly express TRAIL,
      but not Fas ligand or TNF, after activation with interferon (IFN)-gamma or -alpha
      and acquire the ability to kill tumor cells. Monocyte-mediated tumor cell
      apoptosis was TRAIL specific, as it could be inhibited with soluble TRAIL
      receptor. Moreover, IFN stimulation caused a concomitant loss of TRAIL receptor 2
      expression, which coincides with monocyte acquisition of resistance to TRAIL
      mediated apoptosis. These results define a novel mechanism of monocyte-induced
      cell cytotoxicity that requires TRAIL, and suggest that TRAIL is a key effector
      molecule in antitumor activity in vivo.

PMID- 10209051
TI  - Lineage-specific requirement for signal transducer and activator of transcription
      (Stat)4 in interferon gamma production from CD4(+) versus CD8(+) T cells.
AB  - CD4(+) and CD8(+) T cells exhibit important differences in their major effector
      functions. CD8(+) T cells provide protection against pathogens through cytolytic
      activity, whereas CD4(+) T cells exert important regulatory activity through
      production of cytokines. However, both lineages can produce interferon (IFN)
      gamma, which can contribute to protective immunity. Here we show that CD4(+) and
      CD8(+) T cells differ in their regulation of IFN-gamma production. Both lineages
      require signal transducer and activator of transcription (Stat)4 activation for
      IFN-gamma induced by interleukin (IL)-12/IL-18 signaling, but only CD4(+) T cells
      require Stat4 for IFN-gamma induction via the TCR pathway. In response to
      antigen, CD8(+) T cells can produce IFN-gamma independently of IL-12, whereas
      CD4(+) T cells require IL-12 and Stat4 activation. Thus, there is a lineage
      specific requirement for Stat4 activation in antigen-induced IFN-gamma production
      based on differences in TCR signaling between CD4(+) and CD8(+) T cells.

PMID- 10209053
TI  - [Prevention of neonatal infection caused by group B streptococci].

PMID- 10209054
TI  - [Prevalence of urinary infections in the community and their susceptibility to
      cefixime].
AB  - The aim of this study was to determine the prevalence of the microorganisms
      causing uncomplicated acute urinary tract infections in the community and their
      susceptibility to cefixime and another six antimicrobials in frequent use in
      Spain. In 1998, we conducted an open, prospective study of 1,000 consecutive
      patients in five large provincial capitals who had positive urine culture, met
      the inclusion criteria, and were referred to the microbiology laboratory for
      urinalysis on an outpatient basis. The procedures for sample collection,
      transportation, laboratory techniques and the evaluation criteria were the same
      in all cases. The prevalence of the microorganisms found was similar to that
      published in the last few years by authors of various studies in Spain.
      Escherichia coli was the most frequently isolated bacteria (82.67% of the Gram
      negative bacteria). The decrease in susceptibility of the isolates to the
      antimicrobials most empirically used was confirmed in these infections at the
      general practitioner's. Therefore, it is suggested that cefixime, an oral
      cephalosporin with the greatest activity against these microorganisms, is useful.

PMID- 10209055
TI  - [Comparison of two methods for the study of the in vitro susceptibility to
      sertaconazole of yeast clinical isolates].
AB  - We evaluated a commercial method for studying the in vitro susceptibility to
      sertaconazole based on its diffusion in agar with standardized tablets, with the
      aim of determining its correlation with the method of microdilution in Shadomy
      modified liquid medium (YNBg). A total of 110 Candida genus strains (50 C.
      albicans, 26 C. tropicalis, 15 C. glabrata, 8 C. parapsilosis, 8 C. krusei, 2 C.
      guilliermondii and 1 C. kefyr) from pathological clinical processes were used.
      The results of both techniques showed a statistically significant correlation
      that depended on the type of reading used in the liquid medium microdilution
      technique, with results being -0. 4199 with IC50; -5135 with IC90: -0.6634 with
      MIC24 h; and -0.4945 with MIC48 h. These values demonstrate the existence of a
      correlation for sertaconazole, and that it is bigger when it is compared with the
      logarithm of the MIC obtained after 24 hours of incubation.

PMID- 10209056
TI  - Bacteriostatic and bactericidal activity of ranitidine bismuth citrate in
      Helicobacter pylori clinical isolates.
AB  - Ranitidine bismuth citrate is a novel salt that seems to be useful in eradication
      of Helicobacter pylori from gastric mucosa when it is combined with antibiotics.
      The in vitro bacteriostatic (by MIC determination) and bactericidal (by killing
      curve) activity of ranitidine bismuth citrate was determined in this study. A
      total of 52 strains were cultured from gastric antral biopsy specimens taken at
      routine endoscopy and identified using standard methodology. MIC was determined
      by agar dilution using Mueller-Hinton agar supplemented with 7% horse blood.
      Killing curves were studied in 11 isolates. Ranitidine bismuth citrate at final
      concentrations of 1 mg/l and 8 mg/l were used. A starting inoculum of 10(4) to
      10(6) CFU/ml was prepared in BHI with 10% fetal calf serum from a 48 h H. pylori
      broth culture. Viable colony counting was performed at 0, 2, 4, 6, 8 and 24 h. A
      control without the study drug was included in each experiment and treated
      identically. A reduction of 100 to 1,000 CFU/ml was considered bactericidal. The
      MIC50, MIC90 and range for ranitidine bismuth citrate was 1, 2 and 0.25-4 mg/l,
      respectively. At 1 mg/l it showed a bactericidal effect after 2 h in one strain,
      after 8 h in two and after 24 h in four strains, and four strains were not
      killed. At 8 mg/l it killed three strains in 2 h, one in 4 h, two in 6 h, one in
      8 h and four strains in 24 h. Ranitidine bismuth citrate was active in vitro
      against the H. pylori clinical isolates tested (by MIC and killing curves).

PMID- 10209058
TI  - Xenotransplantation--state of the art--update 1999.
AB  - Organ transplantation is limited by the number of cadaveric human donor organs
      that become available. Xenotransplantation - the transplantation of organs and
      tissues between animal species - would supply an unlimited number of organs and
      offer many other advantages. The pig has been identified as the most suitable
      donor animal. Pig organs, when transplanted into humans or nonhuman primates,
      are, however, rejected hyperacutely within minutes by antibody-mediated
      complement activation. Human anti-pig antibodies have been identified as being
      directed against galactose alpha 1-3galactose (alpha Gal) epitopes on pig
      vascular endothelium. Methods have been successfully developed to prevent
      hyperacute rejection. These include (i) depletion or inhibition of recipient
      antibodies or complement and (ii) development of transgenic pigs that express a
      human complement-regulatory protein (e.g. hDAF). The persistence or return of
      anti-pig antibody, however, even following the use of hDAF pig organs, eventually
      leads to what has been variously termed "acute vascular rejection" or "delayed
      xenograft rejection", which is again believed to be largely antibody-dependent.
      Nevertheless, experimental pig-to-primate organ xenotransplantation now results
      in transplant function for days and weeks rather than minutes. Little is yet
      known of the nature of the acute cellular rejection response that is anticipated
      to follow, and of any subsequent chronic rejection that may develop. Tolerance to
      both the alpha Gal epitope and to swine leukocyte antigens (SLA) is being
      explored using gene therapy techniques and by the induction of hematopoietic cell
      chimerism. The development of genetically engineered pigs that do not express the
      alpha Gal epitope is also being pursued. Considerable progress has been made in
      recent years, but experimental results do not yet warrant the initiation of a
      clinical trial of organ xenotransplantation. However, trials are already underway
      of pig cell transplants in patients with diabetes and neurodegenerative
      conditions, such as Parkinson's disease.

PMID- 10209060
TI  - [Aspergillosis].

PMID- 10209059
TI  - Comparison of calcium import as a function of contraction in the aortic smooth
      muscle of Sprague-Dawley, Wistar Kyoto and spontaneously hypertensive rats.
AB  - Genetic variations of far-reaching consequences have been established between
      spontaneously hypertensive rats (SHR) and their controls, Wistar Kyoto rats
      (WKY). The SHR strain is the most widely used model for the study of genetic
      hypertension. Calcium homeostasis in the vascular smooth muscle (VSM) is
      controlled by calcium channels and calcium pumps located in both VSM and the
      overlying endothelial cells that line the large blood vessels and the heart.
      Hypertension adversely affects calcium homeostasis. Investigations on the import
      of calcium from extracellular spaces with alpha1-adrenergic stimulation as a
      function of contractility of VSM cells in SHR and WKY were made and compared with
      the contractility observed in VSM cells of Sprague-Dawley (CD) rats. Experiments
      were performed on rings from thoracic aortas of three strains with endothelial
      lining intact or removed to discern the paracrine control of endothelium on
      contractility in response to calcium import. The internal stores of Ca2+ were
      depleted by repeated alpha 1-adrenergic stimulation with phenylephrine (PE) and
      refilling of these stores was prevented by cyclopiazonic acid (CPA) and/or
      thapsigargin (TG), two known inhibitors of Ca2+ATPase, the enzyme that drives
      sarcoplasmic calcium pumps. The two components of tonic muscular contraction, T I
      and T II, which are known to be due to the flow of Ca2+ from the extracellular
      gradient controlled via the poly-phosphoinositide cascade and nifedipine
      sensitive Ca2+ channels were found to be variable among these strains.
      Implications of these variations are discussed in this report

PMID- 10209061
TI  - [Prophylaxis and treatment of respiratory infections caused by influenza virus
      types A and B].

PMID- 10209062
TI  - [Safety of fluoroquinolones 10 years later].

PMID- 10209063
TI  - [In vitro activity of fluoroquinolones and oral beta lactam antibiotics against
      clinical isolates of Escherichia coli].
AB  - We studied the in vitro activity of amoxicillin-clavulanic acid, cefprozil,
      cefuroxime, cefpodoxime, ceftibuten, cefixime, ciprofloxacin and sparfloxacin
      against 400 strains of Escherichia coli. The strains were obtained from urine
      cultures from patients with community acquired urinary tract infection who were
      treated in our hospital in 1997 and 1998. Among the six betalactams, ceftibuten
      and cefixime were the most active in vitro with MIC90 of 0.5 mg/l. Both
      antimicrobials were 2- and 16-fold more active than cefpodoxime (MIC90 1 mg/l)
      and cefprozil (MIC90 8 mg/l), respectively. However, overall, the four
      cephalosporins inhibited between 95% and 99% of isolates. Cefuroxime and
      amoxicillin-clavulanic acid showed less activity with a MIC90 of 16 mg/l. The
      percentage of fluoroquinolone-resistant strains was 24% with a similar activity
      to ciprofloxacin (MIC90 32 mg/l) and sparfloxacin (MIC90 64 mg/l).

PMID- 10209064
TI  - [Asthma and infection: etiopathogenic factors and treatment with roxithromycin].

PMID- 10209065
TI  - Binding of nuclear proteins to the negative regulatory element of the IL-2 gene
      in lymphocytes from rheumatic patients.
AB  - T lymphocytes from several autoimmune diseases including rheumatoid arthritis
      (RA) and systemic lupus erythematosus (SLE) exhibit deficient mitogenic response
      in terms of proliferation and IL-2 production. The expression of the IL-2 gene is
      regulated by various transcription factors. One of these factors suppresses IL-2
      expression and binds to the negative responsive element in the IL-2 gene 5'
      flanking region (NRE-A). The authors hypothesized that the decreased production
      of IL-2 by T cells from RA and SLE patients is at least partially caused by high
      expression of the NRE-A binding protein. To test this hypothesis T cells from
      healthy donors and patients with RA and SLE were stimulated. Using the
      electrophoretic mobility shift assay we detected NRE-A DNA-binding proteins in
      the nuclei of the stimulated cells. No difference was found between NRE-A DNA
      binding in nuclear extracts of T cells taken from healthy donors and those taken
      from patients. The specificity of the DNA-protein interactions was ascertained
      through the use of unlabeled DNA competitors. No correlation was found between
      DNA-binding and the patients' disease duration or medication. In conclusion,
      decreased IL-2 biosynthesis by T lymphocytes from RA and SLE patients can not be
      explained by abnormal expression of the NRE-A DNA-binding protein.

PMID- 10209066
TI  - Ciliary neurotrophic factor and phorbol ester each decrease selected STAT3 pools
      in neuroblastoma cells by proteasome-dependent mechanisms.
AB  - Many cytokines and growth factors activate common signal transduction pathways
      and yet are able to elicit distinct cell-specific responses. We are defining
      mechanisms regulating signalling molecules in order to understand how cytokines
      can produce unique responses. It was found that individual members of the signal
      transducer and activator of transcription (STAT) family are regulated by ciliary
      neurotrophic factor (CNTF) and by protein kinase C. Treatment of SH-SY5Y human
      neuroblastoma cells with the phorbol ester, 12- O -tetradecanoylphorbol 13
      acetate (TPA), for 4-5 h caused a 60% decline in both STAT2 and STAT3 levels and
      no decline in levels of STATs 1, 5 or 6, or in Jaks 1 or 2. The decline in STAT3
      was inhibited by treatment with MG132, an inhibitor of proteasome-dependent
      protein degradation. Treatment of cells with CNTF induced a rapid tyrosine
      phosphorylation of STAT3 followed by a time-dependent decay of this signal. Loss
      of tyrosine phosphorylated STAT3 was inhibited by MG132 but did not require
      protein kinase C activity. These results suggest that STAT3 availability can be
      controlled by proteasome-dependent pathways activated either by protein kinase C
      or by cytokines.

PMID- 10209067
TI  - Calcitonin gene-related peptide (CGRP) increases intracellular free Ca2+
      concentrations but not cyclic AMP formation in CGRP receptor-positive
      osteosarcoma cells (OHS-4).
AB  - Although calcitonin gene-related peptide (CGRP) may act as a local factor in
      bone, its mechanisms of action on osteoblasts are not well understood. We
      previously showed the presence of CGRP transcripts and peptide in human OHS-4
      osteoblastic cells. The authors investigated the expression of CGRP receptor
      (CGRP-R) and its intracellular signalling properties in OHS-4 cells. Semi
      quantitative RT-PCR analysis showed that OHS-4 cells express much more CGRP-R
      than calcitonin (CT)-R transcripts. After amplification of CGRP-R by RT-PCR and
      cloning of amplified fragments, the predicted CGRP-R sequence in OHS-4 cells was
      found to share 100% identity with human lung CGRP-R. Biochemical analysis showed
      that hCGRP did not increase intracellular cAMP levels in synchronized OHS-4 cells
      whatever was the cell cycle position. However, adenylate cyclase activity was
      functional, as human parathyroid hormone increased cAMP levels. In contrast,
      hCGRP induced a rapid, transient and dose-dependent increase in free cytosolic
      calcium levels. The data show that CGRP increases intracellular free
      Ca2+concentration but is not coupled to adenylate cyclase in CGRP receptor
      positive OHS-4 osteosarcoma cells, suggesting that CGRP induces downstream events
      driven by phospholipase C in these cells.

PMID- 10209069
TI  - Downregulation of connexin 43 gene expression in rat heart during inflammation.
      The role of tumour necrosis factor.
AB  - Gap junctions form channels that mediate the communication between adjacent
      cells. Alterations in gap junction function and/or expression are believed to
      contribute to cardiac dysfunction such as those observed in septic patients. The
      expression of connexin 43 (Cx43), the subunit component of the most abundant
      cardiac gap junction, was analysed in rat heart during inflammation induced by
      the administration of bacterial lipopolysaccharide (LPS). Cx43 mRNA levels were
      found to be dramatically (>50%) and rapidly (2 h) reduced in the heart after
      injection of LPS (1 mg/kg). To investigate the possible mechanism of the decrease
      in Cx43 expression during inflammation, the promoter region of this gene was
      cloned. The basal Cx43 promoter activity was observed within 224-134 bp of the
      transcriptional initiation site after transfection into a rat myoblast cell-line
      (H9c2). The Cx43 promoter activity was found to be reduced by incubation of the
      transfected cells with serum obtained from LPS-treated rats. Moreover, Cx43
      promoter activity was also decreased upon incubation with tumour necrosis factor
      alpha. These results suggest that Cx43 expression in the heart can be modulated
      by circulating cytokines. These observations may have important implications in
      the depression of heart function observed in septic patients.

PMID- 10209068
TI  - Inhibitors of Src-family tyrosine kinases favour Th2 differentiation.
AB  - Two potent pyrazolo-pyrimidine inhibitors of Src-family kinases were found to
      enhance interleukin 4 (IL-4) and reduce interferon gamma(IFN-gamma) production in
      cultures of splenocytes from ovalbumin-specific TCR-transgenic BALB/c mice. The
      effect was increased by addition of a monoclonal antibody binding to domains 3/4
      of CD4, while other antibodies binding to domain 1 had the opposite effect. The
      inhibitors suppressed CD40 ligand (CD40L) expression on activated CD4 T cells,
      which may explain this Th2 differentiating effect. More generally, the effect
      fits within the overall framework of signal attenuation in T cells driving this
      form of differentiation. The inhibitors did not revert previously induced Th1
      differentiation in serial cultures of the TCR-transgenic cells. Drugs with this
      activity are of obvious interest as probes and potential therapeutic agents in
      autoimmune disease.

PMID- 10209070
TI  - Effects of repeated injections of interleukin 1beta or lipopolysaccharide on the
      HPA axis in the newborn rat.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis is stimulated during immune and
      inflammatory processes. Interleukin 1beta (IL-1beta) and lipopolysaccharide (LPS)
      are known to be potent stimulators of this axis. During postnatal development,
      the rat seems to be hyporesponsive to many stimuli. The effects of repeated
      systemic injections of IL-1beta and LPS on the HPA axis were investigated in
      neonatal rats. IL-1beta (0.02 microg/pup, administered twice daily from postnatal
      day 1 to 4) induced marked elevation in plasma corticosterone (CORT) level as
      compared to controls and LPS groups (0.4 microg or 1.2 microg LPS/pup, injected
      once daily from postnatal day 1 to 4). Adrenal wet weight was significantly
      higher, thymus weight was significantly lower. In contrast to the organ weights,
      there were no differences in CORT concentrations between LPS-exposed groups and
      controls. However, the weights of the adrenals in rats treated with LPS were
      significantly increased in a dose-dependent manner as compared to controls. The
      high LPS dose was associated with significantly lower thymus weights as compared
      to controls and 0.4 microg LPS rats. Thymus weights were significantly lower
      following IL-1beta- than LPS-administration. It is supposed that a developing
      endotoxin tolerance could account for the observed absence of CORT rise after the
      last LPS injection.

PMID- 10209071
TI  - Inhibition of GROalpha-induced human endothelial cell proliferation by the alpha
      chemokine inhibitor antileukinate.
AB  - GROalpha, an autocrine mitogenic factor for melanoma cell lines, belongs to the
      superfamily of alpha-chemokines. Here, we report that GROalpha stimulates the
      growth of human umbilical vein endothelial cells (HUVEC) in vitro, with
      proliferation being significantly stimulated by 100 nM recombinant human (rh)
      GROalpha. Proliferation was significantly inhibited by 100 microg/ml anti- human
      GROalpha monoclonal antibody (mAb), while excess GROalpha restored the growth.
      The addition of rhIL-8, rhIP-10, anti-human IL-8 or anti-human ENA-78 mAbs did
      not alter HUVEC proliferation. [125I]IL-8 binding to HUVEC was saturable and
      inhibited by non-radioactively iodinated IL-8, but not non-iodinated IL-8.
      [125I]GROalpha binding was also inhibited by iodinated IL-8. Since these data
      suggested specific binding sites for alpha-chemokines on HUVEC, we tested the
      effect of antileukinate, a potent alpha-chemokine receptor inhibitor, on
      [125I]GROalpha binding. Antileukinate inhibited GROalpha binding and suppressed
      HUVEC proliferation in a dose-dependent manner. Antileukinate was not cytotoxic,
      with no decrease in cell viability in the presence of 100 microM antileukinate.
      These findings suggest that GROalpha is essential for HUVEC growth factor and
      that antileukinate inhibits growth by preventing autocrine GROalpha receptor
      binding. This raises the interesting possibility of alpha-chemokine receptor
      inhibitors, such as antileukinate, in the treatment of cancer where angiogenesis
      is an important factor for tumour growth.

PMID- 10209073
TI  - Energy storage and cytokine response in patients undergoing liver
      transplantation.
AB  - Overproduction of pro-inflammatory cytokines during surgery has been known to
      exert tissue-damaging and lethal effects on the host. Hypermetabolism-associated
      malnutrition, a common feature of patients with end-stage liver diseases, is
      related to the presence of a systemic inflammatory response, as reflected by
      enhanced levels of proinflammatory cytokines. The present study was designed to
      evaluate energy status of 29 liver transplant recipients, and to assess the
      relation of energy storage to post-operative cytokine response. The glycogen
      contents of the graft, and the recipient's abdominal muscle and old liver were
      measured. The plasma concentrations of tumour necrosis factor alpha, interleukin
      1beta, interleukin 6, lactate, pyruvate and total ketone bodies were determined
      during and after surgery. In undernourished patients, ketone bodies seemed to be
      the major fuel available to muscle. The concentration of ketone bodies decreased
      rapidly after the incision, and remained at a low level after reperfusion. These
      patients had higher plasma levels of lactate/pyruvate ratio and aromatic amino
      acids during the anhepatic phase, followed by an exaggerated response of
      cytokines. Depletion of energy storage of the recipients may be involved in the
      deterioration of peri-operative energy metabolism and the exaggerated post
      operative cytokine response.

PMID- 10209072
TI  - IL-1alpha but not IL-1beta-induced prostaglandin synthesis is inhibited by
      corticotropin-releasing factor.
AB  - Interleukin (IL)-1alpha and IL-1beta share low amino acid homology, but exhibit a
      very similar array of biological activities. The authors previously showed
      negative regulation of IL-1alpha-induced prostaglandin (PG) production by
      corticotropin releasing factor (CRF). In this study, the authors compared the
      effect of CRF on IL-1alpha- and IL-1beta-induced PG synthesis. IL-1alpha (100
      U/ml) increased prostacyclin (PGI2) (measured as 6-keto PGF1alpha[6K]) synthesis
      in endothelial cells and the production of PGE2in fibroblasts. The PG response to
      IL-1alpha was suppressed by simultaneous exposure to CRF (2.5x10(-11)-2.5x10(-8)
      M) in both cell types. IL-1alpha enhanced both phospholipase A2(PLA2) and
      prostaglandin H synthase (PGHS) activities, and the two effects were completely
      abrogated by CRF. IL- 1beta (100 U/ml) was as active as IL-1alpha in triggering
      release of PGI2 from endothelial cells and PGE2 from fibroblasts. However, CRF
      (2.5x10(-11)-2.5x10(-8) M) failed to alter the IL-1beta-induced PG synthesis in
      both cell types. Following IL-1beta PGHS activity, and to a lesser extent PLA2
      activity, were enhanced, however CRF only inhibited PGHS and not PLA2 activity.
      It is concluded that although IL-1alpha and IL-1beta usually produce similar
      biological effects, here they seem to act via different mechanisms. The different
      regulation of IL-1alpha and IL-1beta pro-inflammatory activities by CRF may
      attribute special precision and specificity to the neuroendocrine-immune control
      of inflammatory processes.

PMID- 10209076
TI  - Salt-sensitivity classification in normotensive adults.
AB  - The objectives of this study were to assess the reliability, sensitivity and
      specificity of salt-sensitivity classification in normotensive adults and to
      determine the predictive power of four clinical indices for salt-sensitivity. A
      total of 66 healthy, normotensive, free-living adults were administered 11-day
      salt-sensitivity diagnostic dietary salt challenges on two occasions to permit
      assessment of classification test-retest reliability. An oral glucose tolerance
      test, an acute saline loading test, gustatory testing and determination of
      salivary flow and sodium concentration were carried out to assess (by correlation
      analysis) their predictive power for salt-sensitivity. Following these
      procedures, 21 participants followed a reduced-sodium diet for 4 months, during
      which blood pressure was monitored monthly to allow evaluation of salt
      sensitivity classification sensitivity and specificity. Regression was used to
      develop a predictive model for salt-sensitivity. Salt-sensitivity classification
      was not highly reliable (kappa-value=0.38), sensitive (0.73) or specific (0.60).
      No single index was highly predictive of classification status, but a model
      composed of five indices accounted for 92% of the variance in blood pressure
      response to acute salt challenge. The dietary salt challenge procedure used here
      for salt-sensitivity classification of normotensive adults had low test-retest
      reliability. While a battery of easily measured attributes may facilitate rapid
      salt-sensitivity classification, such a diagnosis provides only limited insight
      regarding blood pressure responsiveness to chronic dietary salt restriction in
      normotensive adults.

PMID- 10209075
TI  - Lisinopril improves arterial function in hyperlipidaemia.
AB  - Endothelial function is defective in hypercholesterolaemia, and animal models
      have suggested that angiotensin-converting enzyme inhibitors may prevent arterial
      damage. We studied the effect of 6 months treatment with lisinopril on
      endothelial function in a group of patients with hypercholesterolaemia. Forty
      patients were studied. Forearm blood flow responses to acetylcholine and sodium
      nitroprusside were assessed by venous occlusion plethysmography. Subjects were
      then randomized in a double-blind fashion to receive either lisinopril, 20 mg/day
      (n=20), or placebo (n=20) for 6 months. Plethysmography was then repeated.
      Baseline variables between groups were comparable. In the lisinopril group blood
      pressure fell significantly [systolic: 145+/-4 to 128+/-4 mmHg (P<0.001);
      diastolic: 84+/-2 to 74+/-2 mmHg (P<0.001)]. An improvement was found in the
      vasodilatory response (expressed as a ratio of the infused/control arm) to
      acetylcholine, e.g. 3.33+/-0.3 (pre) versus 4.45+/-0.48 (post) at 30 microg/ml
      (P<0.03), and also to nitroprusside, e.g. 3.0+/-0.2 (pre) versus 3.86+/-0.3
      (post) at 3.2 microg/ml (P<0.01). In the placebo group vasodilatation did not
      change significantly in response to acetylcholine, and nitroprusside responses
      were unchanged. The data presented suggest that 6 months of lisinopril therapy
      have a beneficial effect on arterial function in subjects with hyperlipidaemia.
      Further work should now investigate whether angiotensin-converting enzyme
      inhibitors are beneficial in reducing mortality and morbidity in
      hypercholesterolaemia.

PMID- 10209077
TI  - Faecal peritonitis causes oedema and neuronal injury in pig cerebral cortex.
AB  - Encephalopathy is a common complication of sepsis. However, little is known about
      the morphological changes that occur in the brain during sepsis. Faecal
      peritonitis was induced in pigs that were killed 8 h later and frontal cortex
      samples were taken immediately after death. The tissue was investigated using
      light and electron microscopy and compared with frontal cortex samples taken from
      sham-operated controls. Septic pigs had 49.5% more perimicrovessel oedema than
      sham pigs. However, the tight junctions between cerebral microvessel endothelial
      cells appeared morphologically intact in both septic and sham pigs. Sepsis also
      resulted in neuronal injury, disruption of astrocytic end-feet and swollen,
      rounded erythrocytes. These morphological changes may be sufficient to underlie
      the clinical features seen in septic encephalopathy.

PMID- 10209078
TI  - Effects of ursodeoxycholic acid on systemic, renal and forearm haemodynamics and
      sodium homoeostasis in cirrhotic patients with refractory ascites.
AB  - Systemic arterial vasodilatation has been implicated in the pathogenesis of
      sodium retention in cirrhosis. Hydrophobic bile acids, which have vasodilatory
      actions, may be involved. Ursodeoxycholic acid, a hydrophilic bile acid, could
      potentially decrease systemic arterial vasodilatation, possibly due to its
      antioxidant effects, and improve sodium handling in cirrhosis. The effects of
      ursodeoxycholic acid on systemic, renal and forearm haemodynamics, liver function
      and renal sodium handling were assessed in vasodilated cirrhotic patients with
      refractory ascites treated with a transjugular intrahepatic porto-systemic shunt
      (TIPS). Eight cirrhotic patients with refractory ascites without TIPS placement
      served as controls for the sodium handling effects of ursodeoxycholic acid. From
      1 month post TIPS, seven patients were studied before, after 1 month of treatment
      with ursodeoxycholic acid (15 mg.day-1.kg-1) and at 1 month follow-up. Lipid
      peroxidation products were used as indices of its antioxidant effects.
      Ursodeoxycholic acid caused a significant reduction in sodium excretion in both
      groups (P<0.05). This, in the post-TIPS patients (urinary sodium excretion: 35+/
      8 mmol/day at 1 month versus 93+/-21 mmol/day at baseline, P<0.05), was due to a
      significant increase in sodium reabsorption proximal to the distal tubule
      (P<0.05), without any significant changes in systemic, renal or forearm
      haemodynamics, or in liver function. No significant change in lipid peroxidation
      products was observed. We conclude that: (i) in cirrhotic patients with
      refractory ascites, ursodeoxycholic acid causes sodium retention, (ii) the
      abnormality in sodium handling in the post-TIPS cirrhotic patients appears to be
      the result of a direct effect on the proximal nephron, suggesting that factors
      other than systemic vasodilatation also contribute to sodium retention in
      cirrhosis, (iii) caution should be exercised in administering ursodeoxycholic
      acid in cirrhotic patients with ascites.

PMID- 10209079
TI  - Splanchnic and systemic haemodynamic response to volume changes in patients with
      cirrhosis and portal hypertension.
AB  - We investigated the haemodynamic response to volume depletion and subsequent
      repletion in patients with cirrhosis and portal hypertension. Twelve patients
      with compensated cirrhosis and portal hypertension were included in the study.
      The haemodynamic changes occurring after removal of approx. 15% of the blood
      volume, and subsequently after isovolume repletion with colloid, were assessed.
      Baseline haemodynamic measurements showed increased cardiac output and a systemic
      vascular resistance at the lower limit of normal. The hepatic venous pressure
      gradient (HVPG) was increased, at 18 mmHg. After depletion, arterial pressure,
      cardiac output and all right-heart-sided pressures decreased, and systemic
      vascular resistance increased. HVPG decreased to 16.0 mmHg. All the above changes
      were statistically significant. After blood volume restitution, the haemodynamic
      values returned to baseline. In particular, an increase in HVPG was shown in four
      out of the twelve patients (two with ascites and two without), which was small in
      three of them. However, HVPG remained the same as or lower than the baseline in
      the other eight patients. Patients with cirrhosis and portal hypertension exhibit
      an abnormal haemodynamic response to blood volume depletion. After volume
      repletion, no increase in the portal pressure was noted in this group of patients
      as a whole, although four out of the twelve patients did show an increase,
      possibly due to extensive collateral circulation.

PMID- 10209080
TI  - Acute effect of ephedrine on 24-h energy balance.
AB  - Ephedrine is used to help achieve weight control. Data on its true efficacy and
      mechanisms in altering energy balance in human subjects are limited. We aimed to
      determine the acute effect of ephedrine on 24-h energy expenditure, mechanical
      work and urinary catecholamines in a double-blind, randomized, placebo
      controlled, two-period crossover study. Ten healthy volunteers were given
      ephedrine (50 mg) or placebo thrice daily during each of two 24-h periods
      (ephedrine and placebo) in a whole-room indirect calorimeter, which accurately
      measures minute-by-minute energy expenditure and mechanical work. Measurements
      were taken of 24-h energy expenditure, mechanical work, urinary catecholamines
      and binding of (+/-)ephedrine in vitro to human beta1-, beta2- and beta3
      adrenoreceptors. Twenty-four-hour energy expenditure was 3.6% greater (8965+/
      1301 versus 8648+/-1347 kJ, P<0.05) with ephedrine than with placebo, but
      mechanical work was not different between the ephedrine and placebo periods.
      Noradrenaline excretion was lower with ephedrine (0.032+/-0.011 microg/mg
      creatinine) compared with placebo (0.044+/-0.012 microg/mg creatinine) (P<0.05).
      (+/-)Ephedrine is a relatively weak partial agonist of human beta1- and beta2
      adrenoreceptors, and had no detectable activity at human beta3-adrenoreceptors.
      Ephedrine (50 mg thrice daily) modestly increases energy expenditure in normal
      human subjects. A lack of binding of ephedrine to beta3-adrenoreceptors and the
      observed decrease in urinary noradrenaline during ephedrine treatment suggest
      that the thermogenic effect of ephedrine results from direct beta1-/beta2
      adrenoreceptor agonism. An indirect beta3-adrenergic effect through the release
      of noradrenaline seems unlikely as urinary noradrenaline decreased significantly
      with ephedrine.

PMID- 10209081
TI  - Co-expression of prepro-adrenomedullin with a putative adrenomedullin receptor
      gene in vascular smooth muscle.
AB  - The prepro-adrenomedullin (prepro-AM) gene encodes several biologically active
      peptides, including the potent vasodilator AM. At least part of the vasodilator
      action of AM appears to be mediated via interactions with receptors on vascular
      smooth muscle cells (VSMC); however, the specific receptors involved are not
      known. The aim of the present study was to identify putative AM receptor genes
      that are co-expressed with AM in cultured rat aortic VSMC that may mediate the
      actions of AM. AM mRNA was shown to be expressed in rat aortic VSMC cultures. In
      acute (4 h) secretion studies, only 20% of the total immunoreactive AM was
      intracellular, with the majority (80%) found in the medium, indicating active
      release of AM peptide from VSMC. Using highly specific ribonuclease protection
      analysis, mRNAs encoding three putative AM receptors [L1, calcitonin-receptor
      like receptor (CRLR) and RDC1] were shown to be present at high concentrations in
      RNA extracts from lung. In cultured VSMC, however, whereas RDC1 mRNA was
      expressed at relatively high concentrations, transcripts encoding CRLR and L1
      were not detected. The co-expression of prepro-AM mRNA with the RDC1 receptor
      implies that AM may act in a localized manner via this receptor to modulate VSMC
      function.

PMID- 10209082
TI  - Dyspnoea, peripheral airway involvement and respiratory muscle effort in patients
      with type I diabetes mellitus under good metabolic control.
AB  - Dyspnoea and pulmonary dysfunction have recently been associated with Type I
      (insulin-dependent) diabetes mellitus. The putative role of altered pulmonary
      mechanics and of performance of inspiratory muscles in inducing dyspnoea has not
      been yet assessed in Type I diabetes. To better focus on this topic we evaluated
      nine patients with Type I diabetes mellitus, aged 19 to 48 years with good and
      stable metabolic control, without a history of smoking and microvascular
      complications, alongside a group of 14 healthy control subjects. In each subject,
      pulmonary volumes, static and dynamic compliance, pleural pressure swings
      (Pplsw), maximal inspiratory pressures (Pplsn), Pplsw(%Pplsn), a measure of
      respiratory muscle effort, and tension-time index [TTI=TI/TTOTxPplsw(%Pplsn)]
      were measured (TI=inspiratory time;TTOT=total time of the respiratory cycle). All
      subjects were studied at baseline and during hypoxic rebreathing. Patients had
      normal pulmonary volumes. During hypoxic rebreathing, a normal change in
      respiratory muscle effort [DeltaPplsw(%Pplsn)/DeltaSaO2] and DeltaTTI/DeltaSaO2,
      and a lower change in tidal volume versus change in oxygen saturation [DeltaVT(%
      vital capacity)/DeltaSaO2], resulted in a higher ratio of respiratory effort to
      tidal volume [Pplsw(%Pplsn)/VT(% vital capacity)], a measure of neuroventilatory
      dissociation of the respiratory pump. Hypoxic dyspnoea, assessed by a modified
      Borg scale, showed a greater rate of rise (DeltaBorg/DeltaSaO2) and a greater
      increase for a given level of respiratory effort in patients. Moreover,
      neuroventilatory dissociation related to the expression of peripheral airway
      involvement, as assessed in terms of low dynamic compliance, and to concurrent
      change in dyspnoea sensation. Patients with Type I diabetes mellitus under good
      metabolic control and with normal lung volumes may have abnormal peripheral
      airway function. The latter is thought to be responsible for the association
      between dyspnoea sensation and neuroventilatory dissociation.

PMID- 10209083
TI  - Impaired skin vasomotor reflexes in patients with erythromelalgia.
AB  - Erythromelalgia (EM) is a chronic disorder characterized by intermittent burning
      pain, warmth and erythema of the extremities. Increasing the local temperature
      and dependency of the affected limb(s) precipitates the symptoms, whereas direct
      cooling and elevation of the limb(s) can provide partial relief. Our previous
      findings showed that patients with EM have enhanced cutaneous vascular tone at
      rest and during stimulation, which may be due to an increase in sympathetic
      neural activity. To test this, we measured skin vasoconstrictor responses to
      contralateral arm cold challenge (CC) and inspiratory gasp (IG) using laser
      Doppler flowmetry at the toe pulp and fingertip. These areas were chosen because
      of their dense sympathetic innervation. An index of the vasoconstrictor response
      (between 0 and 1) was calculated from the change in skin perfusion from baseline
      following CC and IG. In control subjects, vasoconstrictor responses to CC at the
      toe and fingertip were both 0. 70+/-0.02 (mean+/-S.E.M.), which were
      significantly greater (P<0. 001) than corresponding values in patients with EM
      (0.37+/-0.04 and 0.45+/-0.04 respectively). Similarly, vasoconstrictor responses
      to IG were significantly greater (P<0.001) at the toe and fingertip in control
      subjects (0.70+/-0.03 and 0.70+/-0.02 respectively) compared with values in EM
      patients (0.27+/-0.03 and 0.45+/-0.15 respectively). These data show that, in
      contrast with control subjects, patients with EM have diminished sympathetic
      vasoconstrictor responses to both CC and IG. Denervation supersensitivity may
      play a part by increasing vasoconstrictor responses to circulating
      catecholamines, leading to a reduction in skin blood flow. Therefore an interplay
      between neural and vasoactive agents may be involved in the pathophysiology of
      EM.

PMID- 10209084
TI  - Glucocorticoids and insulin resistance: old hormones, new targets.
AB  - Insulin resistance has been proposed as a mediator of the association between
      risk factors for cardiovascular disease in the population. The clinical syndrome
      of glucocorticoid excess (Cushing's syndrome) is associated with glucose
      intolerance, obesity and hypertension. By opposing the actions of insulin,
      glucocorticoids could contribute to insulin resistance and its association with
      other cardiovascular risk factors. In this review, we describe briefly the known
      mechanisms of insulin resistance and highlight the potential mechanisms for the
      effect of glucocorticoids. We then discuss factors which modulate the influence
      of glucocorticoids on insulin sensitivity; this highlights a novel therapeutic
      strategy to manipulate glucocorticoid action which may prove to be a useful tool
      in treating subjects with insulin resistance. Finally, we describe evidence from
      human studies that glucocorticoids make an important contribution to the
      pathophysiology of insulin resistance in the population.

PMID- 10209085
TI  - Pulmonary granulocyte kinetics in relation to endothelial and granulocyte
      activation.
AB  - The aim of the study was to measure the peripheral blood levels of soluble E
      selectin in patients with systemic inflammation and compare them with in vivo
      granulocyte activation, pulmonary intravascular granulocyte pooling, pulmonary
      extravascular granulocyte migration and 99mTc-diethylenetriaminepenta-acetic acid
      (DTPA) aerosol clearance, an index of lung injury. The level of soluble E
      selectin was measured by capture ELISA. Granulocytes were labelled with 111In and
      99mTc for quantification of pulmonary granulocyte kinetics. The pulmonary
      vascular granulocyte pool (PGP) was expressed as a fraction of the total blood
      granulocyte pool. Pulmonary granulocyte migration was quantified on 24-h images
      using the 111In signal. Granulocyte activation was quantified as the percentage
      of circulating cells showing shape change ('primed'). Lung injury was assessed
      from the clearance rate of inhaled 99mTc-DTPA aerosol. Eighteen patients with
      systemic inflammation were studied: five with inflammatory bowel disease, eight
      with systemic vasculitis, four with graft versus host disease and one with a
      recent renal transplant. The peripheral blood levels of soluble E-selectin were
      significantly elevated in patients with systemic inflammation. The level of
      soluble E-selectin showed a significant association with granulocyte migration
      (Spearman rank correlation coefficient, Rs=0.53; P<0.05) but not with PGP or with
      the percentage of cells showing shape change (P>0.05 for both). Granulocyte
      migration was bimodal: patients were therefore subdivided into 'migrators' and
      'non-migrators'. Soluble E-selectin level, 99mTc-DTPA clearance and PGP, but not
      the percentage of cells showing shape change, were significantly higher in
      migrators than in non-migrators. We conclude that pulmonary intravascular
      granulocyte pooling is increased in the presence of increased numbers of
      circulating primed granulocytes but increased pooling does not by itself promote
      granulocyte migration into the lung interstitium. Insofar as an elevated level of
      E-selectin in peripheral blood reflects vascular endothelial activation, the data
      are consistent with the notion that pulmonary endothelial activation is required,
      in addition to granulocyte activation and an expanded PGP, for granulocyte
      migration into lung parenchyma and, therefore, for lung injury to occur.

PMID- 10209087
TI  - Cell division: The renaissance of the centriole.
AB  - Centrioles are located at the center of the cytoskeleton and duplicate exactly
      once per cell cycle. Recent studies suggest that centrioles are required for the
      organization of a functional centrosome and that centriole assembly requires both
      gamma- and delta-tubulin.

PMID- 10209086
TI  - Transcriptional regulation: SWItching circuitry.
AB  - Proteins of the SWI/SNF family disrupt chromatin, hydrolysing ATP in the process.
      How they do so is still mysterious, but recent studies indicate that they can be
      targeted to the nuclear infrastructure and to particular genes, where they
      cooperate with other enzymes to activate or repress transcription.

PMID- 10209088
TI  - Vertebrate genomics: More fishy tales about Hox genes.
AB  - Zebrafish Hox genes are arranged in at least seven clusters, rather than the four
      clusters typical of vertebrates. This suggests that an additional genome
      duplication occurred on the fish lineage and explains why many gene families are
      typically about half the size in land vertebrates than they are in fish.

PMID- 10209089
TI  - Neural development: The semantics of axon guidance.
AB  - Recent studies of the semaphorin family of axon guidance signals and their
      receptors have revealed a surprising versatility in the ways that they can be
      used solve problems in neural development, and provided new opportunities for
      understanding how guidance information is interpreted beneath the cell surface.

PMID- 10209090
TI  - RNA splicing: What has phosphorylation got to do with it?
AB  - Many pre-mRNA splicing factors are phosphorylated in vivo, but the role of this
      modification has been unclear. Recent observations suggest that phosphorylation
      modulates protein-protein interactions within the spliceosome, thereby
      contributing to dynamic structural reorganization of the spliceosome during
      splicing.

PMID- 10209091
TI  - Photomophogenesis: Phytochrome takes a partner!
AB  - How light signals are transduced by phytochromes is still poorly understood.
      Recent studies have provided evidence that a PAS domain protein, PIF3, physically
      interacts with phytochromes, plays a role in phytochrome signal transduction and
      might be a component of a novel signalling pathway in plants.

PMID- 10209092
TI  - Circadian rhythms: Something to cry about?
AB  - Recent studies suggest that a class of proteins known as cryptochromes have an
      evolutionarily conserved role in the entrainment of circadian rhythms to the
      night-day cycle. While the evidence reported is intriguing, the notion that
      cryptochromes have the same role in all species requires further investigation.

PMID- 10209093
TI  - Structure prediction: The state of the art.
AB  - A recent meeting to evaluate the state of the art of protein structure prediction
      saw progress on all fronts; for prediction methods based on comparative modeling
      or fold recognition, the progress was incremental, but in the case of ab initio
      structure prediction, some surprising successes were reported.

PMID- 10209094
TI  - Movement of nuclear poly(A) RNA throughout the interchromatin space in living
      cells.
AB  - BACKGROUND: Messenger RNA (mRNA) is transcribed and processed in the nucleus of
      eucaryotic cells and then exported to the cytoplasm through nuclear pores. It is
      not known whether the movement of mRNA from its site of synthesis to the nuclear
      pore is directed or random. Directed movement would suggest that there is an
      energy-requiring step in addition to the step required for active transport
      through the pore, whereas random movement would indicate that mRNAs can make
      their way to the nuclear envelope by diffusion. RESULTS: We devised a method to
      visualize movement of endogenous polymerase II transcripts in the nuclei of
      living cells. Oligo(dT) labeled with chemically masked (caged) fluorescein was
      allowed to penetrate cells and hybridize to nuclear poly(A) RNA. Laser spot
      photolysis then uncaged the oligo(dT) at a given intranuclear site and the
      resultant fluorescent, hybridized oligo(dT) was tracked using high-speed imaging
      microscopy. Poly(A) RNA moved away from the uncaging spot in all directions with
      a mean square displacement that varied linearly with time, and the same apparent
      diffusion coefficient was measured for the movement at both 37 degrees C and 23
      degrees C. These properties are characteristic of a random diffusive process.
      High resolution three-dimensional imaging of live cells containing both Hoechst
      labeled chromosomes and uncaged oligo(dT) showed that, excluding nucleoli, the
      poly(A) RNA could access most, if not all, of the non-chromosomal space in the
      nucleus. CONCLUSIONS: Poly(A) RNA can move freely throughout the interchromatin
      space of the nucleus with properties characteristic of diffusion.

PMID- 10209095
TI  - The Drosophila ATM homologue Mei-41 has an essential checkpoint function at the
      midblastula transition.
AB  - BACKGROUND: Drosophila embryogenesis is initiated by 13 rapid syncytial mitotic
      divisions that do not require zygotic gene activity. This maternally directed
      cleavage phase of development terminates at the midblastula transition (MBT), at
      which point the cell cycle slows dramatically, membranes surround the cortical
      nuclei to form a cellular blastoderm, and zygotic gene expression is first
      required. RESULTS: We show that embryos lacking Mei-41, a Drosophila homologue of
      the ATM tumor suppressor, proceed through unusually short syncytial mitoses, fail
      to terminate syncytial division following mitosis 13, and degenerate without
      forming cells. A similar cleavage-stage arrest is produced by mutations in
      grapes, which encodes a homologue of the Checkpoint-1 kinase. We present
      biochemical, cytological and genetic data indicating that Mei-41 and Grapes are
      components of a conserved DNA-replication/damage checkpoint pathway that triggers
      inhibitory phosphorylation of the Cdc2 kinase and mediates resistance to
      replication inhibitors and DNA-damaging agents. This pathway is nonessential
      during postembryonic development, but it is required to terminate the cleavage
      stage at the MBT. Cyclins are required for Cdc2 kinase activity, and mutations in
      cyclin A and cyclin B bypass the requirement for mei-41 at the MBT. These
      mutations do not restore wild-type syncytial cell-cycle timing or the embryonic
      replication checkpoint, however, suggesting that Mei-41-mediated inhibition of
      Cdc2 has an additional essential function at the MBT. CONCLUSIONS: The Drosophila
      DNA-replication/damage checkpoint pathway can be activated by externally
      triggered DNA damage or replication defects throughout the life cycle, and under
      laboratory conditions this inducible function is nonessential. During early
      embryogenesis, however, this pathway is activated by developmental cues and is
      required for the transition from maternal to zygotic control of development at
      the MBT.

PMID- 10209096
TI  - Caenorhabditis elegans inhibitor of apoptosis protein (IAP) homologue BIR-1 plays
      a conserved role in cytokinesis.
AB  - BACKGROUND: Inhibitor of apoptosis proteins (IAPs) suppress apoptotic cell death
      in several model systems and are highly conserved between insects and mammals.
      All IAPs contain at least one copy of the approximately 70 amino-acid baculovirus
      IAP repeat (BIR), and this domain is essential for the anti-apoptotic activity of
      the IAPs. Both the marked structural diversity of IAPs and the identification of
      BIR-containing proteins (BIRPs) in yeast, however, have led to the suggestion
      that BIRPs might play roles in other, as yet unidentified, cellular processes
      besides apoptosis. Survivin, a human BIRP, is upregulated 40-fold at G2-M phase
      and binds to mitotic spindles, although its role at the spindle is still unclear.
      RESULTS: We have identified and characterised two Caenorhabditis elegans
      BIRPs,BIR-1 and BIR-2; these proteins are the only BIRPs in C. elegans. The bir-1
      gene is highly expressed during embryogenesis with detectable expression
      throughout other stages of development; bir-2 expression is detectable only in
      adults and embryos. Overexpression of bir-1 was unable to inhibit developmentally
      occurring cell death in C. elegans and inhibition of bir-1 expression did not
      increase cell death. Instead, embryos lacking bir-1 were unable to complete
      cytokinesis and they became multinucleate. This cytokinesis defect could be
      partially suppressed by transgenic expression of survivin, the mammalian BIRP
      most structurally related to BIR-1, suggesting a conserved role for BIRPs in the
      regulation of cytokinesis. CONCLUSIONS: BIR-1, a C. elegans BIRP, is probably not
      involved in the general regulation of apoptosis but is required for embryonic
      cytokinesis. We suggest that BIRPs may regulate cytoskeletal changes in diverse
      biological processes including cytokinesis and apoptosis.

PMID- 10209097
TI  - Horizontal transfer of Wolbachia between phylogenetically distant insect species
      by a naturally occurring mechanism.
AB  - Wolbachia is a genus of alpha-proteobacteria found in obligate intracellular
      association with a wide variety of arthropods, including an estimated 10-20% of
      all insect species [1]. Wolbachia represents one of a number of recently
      identified 'reproductive parasites' [2] which manipulate the reproduction of
      their hosts in ways that enhance their own transmission [3] [4] [5] [6] [7] [8]
      [9]. The influence of Wolbachia infection on the dynamics of host populations has
      focused considerable interest on its possible role in speciation through
      reproductive isolation [3] [10] [11] and as an agent of biological control [2]
      [12] [13]. Although Wolbachia normally undergoes vertical transmission through
      the maternal line of its host population [14], there is compelling evidence from
      molecular phylogenies that extensive horizontal (intertaxon) transmission must
      have occurred [1] [9] [15] [16] [17]. Some of the best candidate vectors for the
      horizontal transmission of Wolbachia are insect parasitoids [15], which comprise
      around 25% of all insect species and attack arthropods from an enormous range of
      taxa [18]. In this study, we used both fluorescence microscopy and PCR
      amplification with Wolbachia-specific primers to show that Wolbachia can be
      transmitted to a parasitic wasp (Leptopilina boulardi) from its infected host
      (Drosophila simulans) and subsequently undergo diminishing vertical transmission
      in this novel host species. These results are, to our knowledge, the first to
      reveal a natural horizontal transfer route for Wolbachia between phylogenetically
      distant insect species.

PMID- 10209098
TI  - Regulation of dauer larva development in Caenorhabditis elegans by daf-18, a
      homologue of the tumour suppressor PTEN.
AB  - The tumour suppressor gene PTEN (also called MMAC1 or TEP1) is somatically
      mutated in a variety of cancer types [1] [2] [3] [4]. In addition, germline
      mutation of PTEN is responsible for two dominantly inherited, related cancer
      syndromes called Cowden disease and Bannayan-Ruvalcaba-Riley syndrome [4]. PTEN
      encodes a dual-specificity phosphatase that inhibits cell spreading and migration
      partly by inhibiting integrin-mediated signalling [5] [6] [7]. Furthermore, PTEN
      regulates the levels of phosphatidylinositol 3,4,5-trisphosphate (PIP3) by
      specifically dephosphorylating position 3 on the inositol ring [8]. We report
      here that the dauer formation gene daf-18 is the Caenorhabditis elegans homologue
      of PTEN. DAF-18 is a component of the insulin-like signalling pathway controlling
      entry into diapause and adult longevity that is regulated by the DAF-2 receptor
      tyrosine kinase and the AGE-1 PI 3-kinase [9]. Others have shown that mutation of
      daf-18 suppresses the life extension and constitutive dauer formation associated
      with daf-2 or age-1 mutants. Similarly, we show that inactivation of daf-18 by
      RNA-mediated interference mimics this suppression, and that a wild-type daf-18
      transgene rescues the dauer defect. These results indicate that PTEN/daf-18
      antagonizes the DAF-2-AGE-1 pathway, perhaps by catalyzing dephosphorylation of
      the PIP3 generated by AGE-1. These data further support the notion that mutations
      of PTEN contribute to the development of human neoplasia through an aberrant
      activation of the PI 3-kinase signalling cascade.

PMID- 10209099
TI  - ASH1 mRNA localization in yeast involves multiple secondary structural elements
      and Ash1 protein translation.
AB  - Localization of ASH1 mRNA to the distal cortex of daughter but not mother cells
      at the end of anaphase is responsible for the two cells' differential mating-type
      switching during the subsequent cell cycle. This localization depends on actin
      filaments and a type V myosin (She1/Myo4). The 3' untranslated region (3' UTR) of
      ASH1 mRNA is reportedly capable of directing heterologous RNAs to a mother cell's
      bud [1] [2]. Surprisingly, however, its replacement has little or no effect on
      the localisation of ASH1 mRNA. We show here that, unlike all other known
      localization sequences that have been found in 3' UTRs, all the elements involved
      in ASH1 mRNA localization are located at least partly within its coding region. A
      77 nucleotide region stretching from 7 nucleotides 5' to 67 nucleotides 3' of the
      stop codon of ASH1 mRNA is sufficient to localize mRNAs to buds; the secondary
      structure of this region, in particular two stems, is important for its
      localizing activity. Two regions entirely within coding sequences, both
      sufficient to localize green fluorescent protein (GFP) mRNA to growing buds, are
      necessary for ASH1 mRNA localization during anaphase. These three regions can
      anchor GFP mRNA to the distal cortex of daughter cells only inefficiently. The
      tight anchoring of ASH1 mRNA to the cortex of the daughter cell depends on
      translation of the carboxy-terminal sequences of Ash1 protein.

PMID- 10209100
TI  - Inverse relationship between systemic resistance of plants to microorganisms and
      to insect herbivory.
AB  - Pre-inoculation of plants with a pathogen that induces necrosis leads to the
      development of systemic acquired resistance (SAR) to subsequent pathogen attack
      [1]. The phenylpropanoid-derived compound salicylic acid (SA) is necessary for
      the full expression of both local resistance and SAR [2] [3]. A separate
      signaling pathway involving jasmonic acid (JA) is involved in systemic responses
      to wounding and insect herbivory [4] [5]. There is evidence both supporting and
      opposing the idea of cross-protection against microbial pathogens and insect
      herbivores [6] [7]. This is a controversial area because pharmacological
      experiments point to negative cross-talk between responses to systemic pathogens
      and responses to wounding [8] [9] [10], although this has not been demonstrated
      functionally in vivo. Here, we report that reducing phenylpropanoid biosynthesis
      by silencing the expression of phenylalanine ammonialyase (PAL) reduces SAR to
      tobacco mosaic virus (TMV), whereas overexpression of PAL enhances SAR. Tobacco
      plants with reduced SAR exhibited more effective grazing-induced systemic
      resistance to larvae of Heliothis virescens, but larval resistance was reduced in
      plants with elevated phenylpropanoid levels. Furthermore, genetic modification of
      components involved in phenylpropanoid synthesis revealed an inverse relationship
      between SA and JA levels. These results demonstrate phenylpropanoid-mediated
      cross-talk in vivo between microbially induced and herbivore-induced pathways of
      systemic resistance.

PMID- 10209101
TI  - Association of the type 1 protein phosphatase PP1 with the A-kinase anchoring
      protein AKAP220.
AB  - The cyclic AMP (cAMP)-dependent protein kinase (PKA) and the type 1 protein
      phosphatase (PP1) are broad-specificity signaling enzymes with opposing actions
      that catalyze changes in the phosphorylation state of cellular proteins.
      Subcellular targeting to the vicinity of preferred substrates is a means of
      restricting the specificity of each enzyme [1] [2]. Compartmentalization of the
      PKA holoenzyme is mediated through association of the regulatory subunits with A
      kinase anchoring proteins (AKAPs), whereas a diverse family of phosphatase
      targeting subunits directs the location of the PP1 catalytic subunit (PP1c) [3]
      [4]. Here, we demonstrate that the PKA-anchoring protein, AKAP220, binds PP1c
      with a dissociation constant (KD) of 12.1 +/- 4 nM in vitro. Immunoprecipitation
      of PP1 from cell extracts resulted in a 10.4 +/- 3.8-fold enrichment of PKA
      activity. AKAP220 co-purified with PP1c by affinity chromatography on microcystin
      sepharos Immunocytochemical analysis demonstrated that the kinase, the
      phosphatase and the anchoring protein had distinct but overlapping staining
      patterns in rat hippocampal neurons. Collectively, these results provide the
      first evidence that AKAP220 is a multivalent anchoring protein that maintains a
      signaling scaffold of PP1 and the PKA holoenzyme.

PMID- 10209102
TI  - Structural elements required for the localization of ASH1 mRNA and of a green
      fluorescent protein reporter particle in vivo.
AB  - The sorting of the Ash1 protein to the daughter nucleus of Saccharomyces
      cerevisiae in late anaphase of the budding cycle correlates with the localization
      of ASH1 mRNA at the bud tip [1] [2]. Although the 3' untranslated region (3' UTR)
      of ASH1 is sufficient to localize a reporter mRNA, it is not necessary, a result
      which indicates that other sequences are involved [1]. We report the
      identification of three additional cis-acting elements in the coding region. Each
      element alone, when fused to a lacZ reporter gene, was sufficient for the
      localization of the lacZ mRNA reporter to the bud. A fine-structure analysis of
      the 3' UTR element showed that its function in mRNA localization did not depend
      on a specific sequence but on the secondary and tertiary structure of a minimal
      118 nucleotide stem-loop. Mutations in the stem-loop that affect the localization
      of the lacZ mRNA reporter also affected the formation of the localization
      particles, in living cells, composed of a green fluorescent protein (GFP)
      complexed with lacZ-ASH1-3' UTR mRNA [3]. A specific stem-loop in the 3' UTR of
      the ASH1 mRNA is therefore required for both localization and particle formation,
      suggesting that complex formation is part of the localization mechanism. An
      analysis on one of the coding-region elements revealed a comparable stem-loop
      structure with similar functional requirements.

PMID- 10209104
TI  - Mitosis in focus 

PMID- 10209103
TI  - Mouse Rad54 affects DNA conformation and DNA-damage-induced Rad51 foci formation.
AB  - Error-free repair by homologous recombination of DNA double-strand breaks induced
      by ionizing radiation (IR) requires the Rad52 group proteins, including Rad51 and
      Rad54, in the yeast Saccharomyces cerevisiae [1]. The formation of a 'joint'
      molecule between the damaged DNA and the homologous repair template is a key step
      in recombination mediated by Rad51 and stimulated by Rad54 [2] [3] [4] [5].
      Mammalian homologs of Rad51 and Rad54 have been identified [2] [3] [6]. Here, we
      demonstrate that mouse Rad54 (mRad54) formed IR-induced nuclear foci that
      colocalized with mRad51. Interaction between mRad51 and mRad54 was induced by
      genotoxic stress, but only when lesions that required mRad54 for their repair
      were formed. Interestingly, mRad54 was essential for the formation of IR-induced
      mRad51 foci. Rad54 belongs to the SWI2/SNF2 protein family, members of which
      modulate protein-DNA interactions in an ATP-driven manner [7]. Results of a
      topological assay suggested that purified human Rad54 (hRad54) protein can unwind
      double-stranded (ds) DNA at the expense of ATP hydrolysis. Unwinding of the
      homologous repair template could promote the formation or stabilization of hRad51
      mediated joint molecules. Rad54 appears to be required downstream of other Rad52
      group proteins, such as Rad52 and the Rad55-Rad57 heterodimer, that assist Rad51
      in interacting with the broken DNA [2] [3] [4].

PMID- 10209106
TI  - The mechanical side of biology.

PMID- 10209105
TI  - Sec14p-like domains in NF1 and Dbl-like proteins indicate lipid regulation of Ras
      and Rho signaling.

PMID- 10209107
TI  - The origins of AIDS.

PMID- 10209108
TI  - Drosophila development: Scalloped and Vestigial take wing.
AB  - The proteins Scalloped and Vestigial are known from genetic studies to play a
      part in Drosophila wing development. Recent results show how they interact with
      each other, and in combination with other transcription factors, to confer
      specific patterns of expression within the wing.

PMID- 10209109
TI  - Membrane transport: Take your fusion partners.
AB  - Recent studies of how vesicles are targeted to fuse with specific membranes
      inside cells highlight a role for extended coiled-coil proteins in tethering
      partner membranes prior to formation of the 'SNARE complex' that mediates the
      fusion reaction. The tethering protein is recruited to membranes by a Rab family
      GTPase

PMID- 10209110
TI  - HIV: The deadly passenger in dendritic cells.
AB  - A picture is emerging of how HIV subverts a normal immunological surveillance
      mechanism to establish primary infection. This involves the infection of
      dendritic cells at mucosal surfaces: as these cells then mature, they transport
      the virus to lymphoid tissue, where viral replication begins and infection of
      CD4(+) T cells occurs.

PMID- 10209112
TI  - Transfer RNA biogenesis: A visa to leave the nucleus.
AB  - Only correctly folded and mature tRNAs can leave the nucleus and enter the
      cytoplasm. Surprisingly, tRNA-aminoacylation has been found to occur, not only in
      the cytosol, but also inside the nucleus, where it may act as an additional
      proofreading step and facilitate the export of 'ready-to-function' aminoacyl
      tRNAs.

PMID- 10209111
TI  - Developmental neurobiology: Alternative ends for a familiar story?
AB  - Somatic DNA recombination is essential for production of functional antigen
      receptor genes of T and B lymphocytes, but it is thought to be unique to the
      immune system. Recent studies have now shown that recombination-related genes are
      also necessary for normal neuronal development.

PMID- 10209114
TI  - Membrane proteins: A tale of barrels and corks.
AB  - Crystal structures have been solved for two bacterial outer membrane proteins,
      FhuA and FepA, which mediate active transport of chelated iron. Analysis of
      ligand-induced changes in the structure of FhuA has provided our first structural
      insights into an active transport mechanism for a complex solute.

PMID- 10209113
TI  - Basement membranes: Putting up the barriers.
AB  - The basement membrane is a highly organized extracellular matrix with adhesive
      and barrier functions. Assembly of this matrix uses two types of cell surface
      receptor, integrins and dystroglycan, to coordinate formation of a polygonal
      network of laminin, a major basement membrane protein.

PMID- 10209115
TI  - Synaptogenesis: The MAP location of GABA receptors.
AB  - Microtubule-associated proteins (MAPs) have been identified as binding partners
      for ionotropic GABAA and GABAC receptors. These interactions suggest a potential
      role for MAPs in the cytoskeletal anchoring of receptor-ion channels at specific
      subcellular sites, such as synapses.

PMID- 10209116
TI  - A DNA unwinding factor involved in DNA replication in cell-free extracts of
      Xenopus eggs.
AB  - BACKGROUND: Alteration of chromatin structure is a key step in various aspects of
      DNA metabolism. DNA unwinding factors such as the high mobility group (HMG)
      proteins are thought to play a general role in controlling chromatin structure
      and a specific role in controlling DNA replication. For instance, in the in vitro
      simian virus 40 replication system, minichromosomes containing HMG-17 replicate
      more efficiently than those without it, suggesting that HMG-17 enhances the rate
      of replication of a chromatin template by unfolding the higher-order chromatin
      structure. At present, however, only limited data suggest an involvement of DNA
      unwinding factors in DNA replication. RESULTS: We purified from Xenopus eggs a
      novel heterodimeric factor, termed DNA unwinding factor (DUF), that consists of
      87 kDa and 140 kDa polypeptides. DUF unwinds closed-circular duplex DNA in the
      presence of topoisomerase I, but it does not possess a DNA gyrase activity: it
      does not introduce negative supercoils into DNA at the expense of ATP hydrolysis.
      Cloning and sequencing of the cDNAs encoding the two polypeptides revealed that
      the 87 kDa polypeptide is homologous to a mammalian HMG protein, T160/structure
      specific recognition protein. The 140 kDa polypeptide is homologous to yeast
      Cdc68, a protein that controls the expression of several genes during the G1
      phase of the cell cycle by modulating chromatin structure. Immunodepletion of DUF
      from Xenopus egg extracts drastically reduced the ability of the extract to
      replicate exogenously added sperm chromatin or plasmid DNA. CONCLUSIONS: We
      propose that DUF plays a role in DNA replication in Xenopus egg extracts.

PMID- 10209117
TI  - Inducible recruitment of Cdc42 or WASP to a cell-surface receptor triggers actin
      polymerization and filopodium formation.
AB  - BACKGROUND: Cdc42, a GTP-binding protein of the Rho family, controls actin
      cytoskeletal organization and helps to generate actin-based protruding
      structures, such as filopodia. In vitro, Cdc42 regulates actin polymerization by
      facilitating the creation of free barbed ends - the more rapidly growing ends of
      actin filaments - and subsequent elongation at these ends. The Wiskott- Aldrich
      syndrome protein, WASP, which has a pleckstrin-homology domain and a Cdc42/Rac
      binding motif, has been implicated in cell signaling and cytoskeleton
      reorganization. We have investigated the consequences of local recruitment of
      activated Cdc42 or WASP to the plasma membrane. RESULTS: We used an activated
      Cdc42 protein that could be recruited to an engineered membrane receptor by
      adding rapamycin as a bridge, and added antibody-coupled beads to aggregate these
      receptors. Inducible recruitment of Cdc42 to clusters of receptors stimulated
      actin polymerization, resulting in the formation of membrane protrusions. Cdc42
      induced protrusions were enriched in the vasodilator-stimulated phosphoprotein
      VASP and the focal-adhesion-associated proteins zyxin and ezrin. The Cdc42
      effector WASP could also induce the formation of protrusions, albeit of different
      morphology. CONCLUSIONS: This is the first demonstration that the local
      recruitment of activated Cdc42 or its downstream effector, WASP, to a membrane
      receptor in whole cells is sufficient to trigger actin polymerization that
      results in the formation of membrane protrusions. Our data suggest that Cdc42
      induced actin-based protrusions result from the local and serial recruitment of
      cytoskeletal proteins including zyxin, VASP, and ezrin.

PMID- 10209118
TI  - The Pds1 anaphase inhibitor and Mec1 kinase define distinct checkpoints coupling
      S phase with mitosis in budding yeast.
AB  - In most eukaryotic cells, DNA replication is confined to S phase of the cell
      cycle [1]. During this interval, S-phase checkpoint controls restrain mitosis
      until replication is complete [2]. In budding yeast, the anaphase inhibitor Pds1p
      has been associated with the checkpoint arrest of mitosis when DNA is damaged or
      when mitotic spindles have formed aberrantly [3] [4], but not when DNA
      replication is blocked with hydroxyurea (HU). Previous studies have implicated
      the protein kinase Mec1p in S-phase checkpoint control [5]. Unlike mec1 mutants,
      pds1 mutants efficiently inhibit anaphase when replication is blocked. This does
      not, however, exclude an essential S-phase checkpoint function of Pds1 beyond the
      early S-phase arrest point of a HU block. Here, we show that Pds1p is an
      essential component of a previously unsuspected checkpoint control system that
      couples the completion of S phase with mitosis. Further, the S-phase checkpoint
      comprises at least two distinct pathways. A Mec1p-dependent pathway operates
      early in S phase, but a Pds1p-dependent pathway becomes essential part way
      through S phase.

PMID- 10209119
TI  - F-box/WD-repeat proteins pop1p and Sud1p/Pop2p form complexes that bind and
      direct the proteolysis of cdc18p.
AB  - Ubiquitin-dependent proteolysis plays an important role in cell-cycle control [1]
      [2]. In budding yeast, the protein Skp1p, the cullin-family member Cdc53p, and
      the F-box/WD-repeat protein Cdc4p form the SCFCdc4p ubiquitin ligase complex,
      which targets the cyclin-dependent kinase (Cdk) inhibitor Sic1p for proteolysis
      [3] [4] [5] [6] [7] [8]. Sic1p is recruited to the SCFCdc4p complex by binding to
      the WD-repeat region of Cdc4p [5] [6], while Skp1p binds to the F-box of Cdc4p
      [9]. In fission yeast, two distinct Cdc4p-related proteins, Pop1p/Ste16p [10]
      [11] and the recently identified Sud1p/Pop2p [12], regulate the stability of the
      replication initiator Cdc18p and the Cdk inhibitor Rum1p. We show here that,
      despite their structural and functional similarities, the pop1 and pop2 genes
      fail to complement each other's deletion phenotypes, indicating that they perform
      non-redundant, but potentially interdependent, functions in proteolysis.
      Consistent with this hypothesis, Pop1p and Pop2p formed heterooligomeric
      complexes when overexpressed, and binding of Cdc18p to Pop2p was dependent on
      Pop1p. The Pop1p-Pop2p interaction was mediated by the amino-terminal domain of
      Pop2p which, when fused to full-length Pop1p, rescued the phenotype of a
      Deltapop1Deltapop2 double mutant. Thus, close physical proximity of two distinct
      F-box/WD-repeat proteins directs proteolysis mediated by the SCFPop ubiquitin
      ligase complex.

PMID- 10209120
TI  - The GRIP domain - a novel Golgi-targeting domain found in several coiled-coil
      proteins.
AB  - Many large coiled-coil proteins are being found associated peripherally with the
      cytoplasmic face of the organelles of the secretory pathway. Various roles have
      been proposed for these proteins, including the docking of donor vesicles or
      organelles to an acceptor organelle prior to fusion, and, in the case of the
      Golgi apparatus, the stacking of the cisternae [1] [2] [3] [4] [5]. Such critical
      roles require accurate recruitment to the correct organelle. For the endosomal
      coiled-coil protein EEA1, targeting requires a carboxy-terminal FYVE domain,
      which interacts with Rab5 and phosphatidylinositol 3-phosphate (PI(3)P), whereas
      the Golgi protein GM130 interacts with Golgi membranes via the protein GRASP65
      [3] [6] [7]. In this paper, we show that two other mammalian Golgi coiled-coil
      proteins, golgin-245/p230 and golgin-97, have a conserved domain of about 50
      amino acids at their carboxyl termini. This 'GRIP' domain is also found at the
      carboxyl terminus of several other large coiled-coiled proteins of unknown
      function, including two human proteins and proteins in the genomes of
      Caenorhabditis elegans and yeasts. The GRIP domains from several of these
      proteins, including that from the yeast protein Imh1p, were sufficient to specify
      Golgi targeting in mammalian cells when fused to green fluorescent protein (GFP).
      This result suggests that this small domain functions to recruit specific coiled
      coil proteins to the Golgi by recognising a determinant that has been well
      conserved in eukaryotic evolution.

PMID- 10209121
TI  - Caspase activation in the terminal differentiation of human epidermal
      keratinocytes.
AB  - The epidermis is a multilayered squamous epithelium in which dividing basal cells
      withdraw from the cell cycle and progressively differentiate as they are
      displaced toward the skin surface. Eventually, the cells lose their nucleus and
      other organelles to become flattened squames, which are finally shed from the
      surface as bags of cross-linked keratin filaments enclosed in a cornified
      envelope [1]. Although keratinocytes can undergo apoptosis when stimulated by a
      variety of agents [2], it is not known whether their normal differentiation
      programme uses any components of the apoptotic biochemical machinery to produce
      the cornified cell. Differentiating keratinocytes have been reported to share
      some features with apoptotic cells, such as DNA fragmentation, but these features
      have not been seen consistently [3]. Apoptosis involves an intracellular
      proteolytic cascade, mainly mediated by members of the caspase family of cysteine
      proteases, which cleave one another and various key intracellular target proteins
      to kill the cell neatly and quickly [4]. Here, we show for the first time that
      caspases are activated during normal human keratinocyte differentiation and that
      this activation is apparently required for the normal loss of the nucleus.

PMID- 10209122
TI  - Embryonic death of Mek1-deficient mice reveals a role for this kinase in
      angiogenesis in the labyrinthine region of the placenta.
AB  - Mek is a dual-specificity kinase that activates the extracellular-signal
      regulated (Erk) mitogen-activated protein (MAP) kinases upon agonist binding to
      receptors. The Erk MAP kinase cascade is involved in cell-fate determination in
      many organisms. In mammals, this pathway is proposed to regulate cell growth and
      differentiation. Genetic studies have shown that although a single mek gene is
      present in Caenorhabditis elegans, Drosophila and Xenopus, two mek homologs, Mek1
      and Mek2, are present in the mammalian cascade. In the present study, we describe
      a mutant mouse line in which the mek1 gene has been disrupted by insertional
      mutagenesis. The null mutation was recessive lethal, as the homozygous mutant
      embryos died at 10.5 days of gestation. Histopathological analyses revealed a
      reduction in vascularization of the placenta that was due to a marked decrease of
      vascular endothelial cells in the labyrinthine region. The failure to establish a
      functional placenta probably explains the death of the mek1-/- embryos. Cell
      migration assays indicated that mek1-/- fibroblasts could not be induced to
      migrate by fibronectin, although the levels of Mek2 protein and Erk activation
      were normal. Re-expression of Mek1 in the mutant mouse embryonic fibroblasts
      (MEFs) restored their ability to migrate. Our findings provide genetic evidence
      that establishes the unique role played by Mek1 in signal transduction. They also
      suggest that mek1 function is required for normal response to angiogenic signals
      that might promote vascularization of the labyrinthine region of the placenta.

PMID- 10209123
TI  - A novel Rab6-interacting domain defines a family of Golgi-targeted coiled-coil
      proteins.
AB  - In recent years, a large number of coiled-coil proteins localised to the Golgi
      apparatus have been identified using antisera from human patients with a variety
      of autoimmune conditions [1]. Because of their common method of discovery and
      extensive regions of coiled-coil, they have been classified as a family of
      proteins, the golgins [1]. This family includes golgin-230/245/256, golgin-97,
      GM130/golgin-95, golgin-160/MEA-2/GCP170, giantin/macrogolgin and a related group
      of proteins - possibly splice variants - GCP372 and
      GCP364[2][3][4][5][6][7][8][9][10][11]. GM130 and giantin have been shown to
      function in the p115-mediated docking of vesicles with Golgi cisternae [12]. In
      this process, p115, another coiled-coil protein, is though to bind to giantin on
      vesicles and to GM130 on cisternae, thus acting as a tether holding the two
      together [12] [13]. Apart from giantin and GM130, none of the golgins has yet
      been assigned a function in the Golgi apparatus. In order to obtain clues as to
      the functions of the golgins, the targeting to the Golgi apparatus of two members
      of this family, golgin-230/245/256 and golgin-97, was investigated. Each of these
      proteins was shown to target to the Golgi apparatus through a carboxy-terminal
      domain containing a conserved tyrosine residue, which was critical for targeting.
      The domain preferentially bound to Rab6 on protein blots, and mutations that
      abolished Golgi targeting resulted in a loss of this interaction. Sequence
      analysis revealed that a family of coiled-coil proteins from mammals, worms and
      yeast contain this domain at their carboxyl termini. One of these proteins, yeast
      Imh1p, has previously been shown to have a tight genetic interaction with Rab6
      [14]. On the basis of these data, it is proposed that this family of coiled-coil
      proteins functions in Rab6-regulated membrane-tethering events.

PMID- 10209124
TI  - A unique talin homologue with a villin headpiece-like domain is required for
      multicellular morphogenesis in Dictyostelium.
AB  - Molecules involved in the interaction between the extracellular matrix, cell
      membrane and cytoskeleton are of central importance in morphogenesis. Talin is a
      large cytoskeletal protein with a modular structure consisting of an amino
      terminal membrane-interacting domain, with sequence similarities to members of
      the band 4.1 family, and a carboxy-terminal region containing F-actin-binding and
      vinculin-binding domains [1] [2]. It also interacts with the cytoplasmic tail of
      beta integrins which, on the external face of the membrane, bind to extracellular
      matrix proteins [3]. The possible roles of talin in multicellular morphogenesis
      in development remain largely unexplored. In Dictyostelium, a eukaryotic
      microorganism capable of multicellular morphogenesis, a talin homologue (TALA)
      has previously been identified and shown to play an important role in cell-to
      substrate adhesion and maintenance of normal elastic properties of the cell [4]
      [5] [6]. Here, we describe a second talin homologue (TALB) that is required for
      multicellular morphogenesis in the development of Dictyostelium. Unlike any other
      talin characterised to date, it contains an additional carboxy-terminal domain
      homologous to the villin headpiece.

PMID- 10209126
TI  - Cell motility exposed 

PMID- 10209125
TI  - A novel Golgi-localisation domain shared by a class of coiled-coil peripheral
      membrane proteins.
AB  - The mechanism by which peripheral membrane proteins are targeted to the
      cytoplasmic face of the Golgi apparatus is poorly understood. Previously, we have
      identified a carboxy-terminal domain of the trans-Golgi-network (TGN) protein
      p230 that is responsible for Golgi localisation [1]. Here, we report the
      identification of a similar Golgi-localisation domain (GLD, also termed the
      'GRIP' domain - see the paper by Munro and Nichols elsewhere in this issue) in a
      family of putative peripheral membrane proteins from lower and higher eucaryotes.
      The majority of family members have a domain structure similar to that of p230,
      with extensive coiled-coil regions (>80%) and the potential GLD located in a non
      coiled-coil domain at the carboxyl terminus. Previously reported proteins in this
      family include human golgin-97 and Saccharomyces cerevisiae Imh1p. By
      constructing chimeric cDNAs encoding carboxy-terminal regions of these family
      members fused to green fluorescent protein (GFP), we have directly demonstrated
      that the GLD of p230, golgin-97, the newly identified human protein GCC1p and
      yeast Imh1p functions as a Golgi-targeting domain in transfected mammalian cells.
      Site-directed mutagenesis of the GLDs identified two conserved aromatic residues
      that are critical for the function of this targeting domain. Endogenous p230 was
      displaced from the Golgi membranes in transfected cells expressing high levels of
      GFP fused to the GLD of either p230 or golgin-97, indicating that different GLDs
      interact with similar membrane determinants. Thus, we have identified a family of
      coiled-coil proteins that share a domain shown to be sufficient for the
      localisation of peripheral membrane proteins to the Golgi apparatus.

PMID- 10209127
TI  - Cynicism and credulity. My word.

PMID- 10209129
TI  - HIV.

PMID- 10209128
TI  - X-chromosome inactivation.

PMID- 10209130
TI  - Mediawatch. Gristle for the mill.

PMID- 10209131
TI  - Production of novel oils in plants.
AB  - We have now isolated the great majority of genes encoding enzymes of storage oil
      biosynthesis in plants. In the past two years, particular progress has been made
      with acyltransferases, ketoacyl-acyl carrier protein synthetases and with
      desaturases and their relatives. In some cases, these enzymes have been
      reengineered to create novel products. Nevertheless, the single or multiple
      insertion of such transgenes into oil crops has not always led to the desired
      phenotype. We are only now beginning to appreciate some of the complexities of
      storage and membrane lipid formation, such as acyl group remodelling and the
      turnover of unusual fatty acids. This understanding will be vital for future
      attempts at the rational engineering of transgenic oil crops. In parallel with
      this, the domestication of plants already synthesising useful fatty acids should
      be considered as a real alternative to the transgenic approach to producing novel
      oil crops.

PMID- 10209132
TI  - Production of new polymeric compounds in plants.
AB  - Plant metabolic engineering has recently enabled the synthesis of a range of
      polyhydroxyalkanoates as well as a protein-based polymer. These novel compounds
      can be harvested from plants as a renewable source of environmentally friendly
      polymers or can be used to change the physical properties of plant products, such
      as fibres.

PMID- 10209133
TI  - Plant natural products: the molecular genetic basis of biosynthetic diversity.
AB  - Significant advances have been made concerning the biosynthesis, regulation and
      genetic manipulation of plant natural products. These include insights into the
      structural biology of isoprenoid cyclization and polyketide condensation
      reactions, a better understanding of the molecular biology of plant cytochrome
      P450s and O-methyltransferases, and new information on the effects of natural
      products on human health.

PMID- 10209134
TI  - Production of modified polymeric carbohydrates.
AB  - The cloning of a gene responsible for the phosphorylation of glucans has made it
      possible to genetically engineer the phosphorylation level of starches in higher
      plants. Through the manipulation of starch synthase activity, it is now also
      possible to genetically tailor the chain-length distribution in the amylopectin.
      Both findings will lead to the development of novel starches utilized as a
      renewable resource. The production of fructans on a large scale can also be
      envisioned for the near future.

PMID- 10209135
TI  - Biosynthetic polypeptide libraries.
AB  - Methodological advances and new applications have fueled significant growth in
      the practice of polypeptide library screening.

PMID- 10209136
TI  - Modifying secretion and post-translational processing in insect cells.
AB  - The baculovirus-insect cell system is a valuable tool for the expression of
      heterologous proteins. Due to limitations in the intracellular processing
      environment, however, heterologous secreted and membrane proteins are often
      insoluble, poorly processed, or contain 'non-human' modifications. Recent
      attempts to modify the insect cell secretory pathway by overexpressing processing
      factors have demonstrated the potential to overcome these limitations.

PMID- 10209137
TI  - Production of new/modified proteins in transgenic plants.
AB  - In recent years, plant biotechnology has almost reached maturity. Transgenic
      plants engineered to be herbicide- or insect-resistant are outcompeting
      conventional crop plants and pest managing strategies leading to a major
      rethinking of the chemical industry. Due to worldwide efforts to study genome
      function, almost any gene of interest is, or will soon be available. Thus,
      identification of gene function will be the major challenge of the next few
      years. In combination with established gene-delivery systems and desired promoter
      and targetting sequences, gene discovery will open a fascinating and new field of
      crop plant design. Transgenic plants engineered to produce superior polypeptides
      have already been created and the first examples are entering clinical and
      industrial trials.

PMID- 10209138
TI  - Engineering of improved microbes and enzymes for bioremediation.
AB  - Bioremediation with microorganisms is an attractive alternative to conventional
      techniques, such as incineration and chemical treatment, for disposing of
      pollutants. Recent progress in molecular biology, microbiology, and genetics is
      providing the driving force towards engineering improved microbes and enzymes for
      bioremediation. A number of genetic engineering approaches have been developed in
      the past several years that have proven useful in introducing/evolving the
      desired properties for different biodegradative pathways or enzymes. The initial
      excitement generated in this area should continue to pave the way for rational or
      irrational design of microbes or enzymes with novel remedial properties.

PMID- 10209140
TI  - Combinatorial biocatalysis: taking the lead from nature.
AB  - Combinatorial biocatalysis is an emerging technology in the field of drug
      discovery. The biocatalytic approach to combinatorial chemistry uses enzymatic,
      chemoenzymatic, and microbial transformations to generate libraries from lead
      compounds. Important recent advances in combinatorial biocatalysis include
      iterative derivatization of small molecules and complex natural products,
      regioselectively controlled libraries, novel one-pot library syntheses, process
      automation, and biocatalyst enhancements.

PMID- 10209139
TI  - Novel coloured flowers.
AB  - The floricultural industry has focused its attention primarily on the development
      of novel coloured and longer living cut flowers. The basis for this was laid down
      some years ago through the isolation of 'blue' genes and ethylene biosynthesis
      genes. Recently, a novel 'blue' gene has been discovered and yellow pigments were
      produced in petunias by addition of a new branch to the phenylpropanoid pathway.
      More insight was obtained into the sequestration of anthocyanin pigments into
      storage vacuoles. Significant progress has been achieved in the commercialisation
      of genetically modified flower varieties.

PMID- 10209141
TI  - Bioactive biomaterials.
AB  - The most important advances in the field of biomaterials over the past few years
      have been in bioactive biomaterials. Materials have been developed to incorporate
      bioactivity through biological recognition, including incorporation of adhesion
      factors, polyanionic sites that mimic the electrostatics of biological regulatory
      polysaccharides, and cleavage sites for enzymes involved in cell migration.
      Materials have also been developed to be active in biological environments by
      undergoing phase changes in situ, including transformations from liquid
      precursors to solids and from soluble materials to materials that are immobilised
      on tissue surfaces.

PMID- 10209142
TI  - Large-scale transient expression in mammalian cells for recombinant protein
      production.
AB  - Large-scale transient expression from mammalian cells is a new technology.
      Breakthroughs have been achieved for non-viral delivery methods: transfections
      can now be done at the 1-10 L scale with mammalian cells grown in suspension.
      Production of 1-20 mg/L of recombinant protein have been obtained in stirred
      bioreactors. Modified alphaviruses have provided a fast and efficient expression
      technology based on viral vectors.

PMID- 10209143
TI  - Public reactions and scientific responses to transgenic crops.
AB  - There is currently intense debate in parts of Europe about the commercial
      production of transgenic food crops. Information from the press and lobbying
      groups has not encouraged an informed and balanced consideration of the issues.
      In marked contrast, there is widespread acceptance of transgenic food crops in
      North America.

PMID- 10209144
TI  - Mathematical models of metabolic pathways.
AB  - There have been recent advances in metabolic flux analysis. In particular, the
      marriage of traditional flux balancing with NMR isotopomer distribution analysis
      holds great promise for the detailed quantification of physiology. Nevertheless,
      flux analysis yields only static snap-shots of metabolism. To robustly predict
      the time evolution of metabolic networks, dynamic mathematical models, especially
      those that contain a description of both gene expression as well as enzyme
      activity, must be utilized. When mechanistic control and regulatory information
      is not available, heuristic-based methods, such as the cybernetic framework, can
      be employed to describe the action of these control mechanisms. In the 'high
      information' future, as more biological information becomes available, such
      heuristic-based approaches can be replaced by mechanistic mass-action
      representations of physiology that stem directly from genetic sequence.

PMID- 10209145
TI  - Plant 'hairy root' culture.
AB  - Due to their fast growth rates and biochemical stability, 'hairy root' cultures
      remain unsurpassed as the choice for model root systems and have promise as a
      bioprocessing system. Applications are wide-ranging, from the production of
      natural products and foreign proteins to a model for phytoremediation of organic
      and metal contaminants. Hairy roots will have a continuing role as an
      experimental model in plant metabolic engineering.

PMID- 10209146
TI  - Production of high-value compounds: carotenoids and vitamin E.
AB  - The unraveling in recent years of the pathways and genes that are responsible for
      biosynthesis of vitamins and carotenoids in plants has provided new molecular
      tools that can be utilized to genetically modify the content and composition of
      these compounds in vivo. There have been recent examples of successful
      manipulation of carotenoid composition and vitamin E activity in plants using
      gene-transfer technology.

PMID- 10209147
TI  - Interactions between mitogenic stimuli, or, a thousand and one connections.
AB  - Signals from G-protein-coupled receptors, tyrosine kinase receptors and integrins
      cooperate to determine cell growth. Work over the past two years has shown that
      this cooperation is based on crosstalk involving both receptors and their
      downstream signaling pathways. These interactions enable cells to integrate
      information from multiple stimuli that regulate cell cycle progression.

PMID- 10209148
TI  - Regulation of tyrosine kinase cascades by G-protein-coupled receptors.
AB  - Mitogenic signaling by G-protein-coupled receptors (GPCRs) involves tyrosine
      phosphorylation of adaptor proteins and assembly of multiprotein Ras activation
      complexes. Over the past three years, three types of scaffolds for GPCR-directed
      complex assembly have been identified: transactivated receptor tyrosine kinases
      (RTKs), integrin-based focal adhesions, and GPCRs themselves. Nonreceptor
      tyrosine kinases play an important role in each case. The processes of GPCR
      desensitization and sequestration via clathrin-coated pits are also involved in
      signaling through the RTK- and GPCR-based scaffolds.

PMID- 10209149
TI  - Epidermal growth factor receptors: critical mediators of multiple receptor
      pathways.
AB  - Recently, the receptor for epidermal growth factor (EGF) was identified as a
      downstream element in different signaling pathways. This expanded its classical
      function as a receptor for EGF-like ligands to a role as mediator of diverse
      signaling systems and as a switch point of a cellular communication network. In
      addition, several downstream targets, (e.g. Smad proteins and STATs) into which
      signals from synergistic and antagonistic signaling pathways converge, were
      identified.

PMID- 10209150
TI  - In or out? Regulating nuclear transport.
AB  - The compartmentalization of proteins within the nucleus or cytoplasm of a
      eukaryotic cell offers opportunity for regulation of cell cycle progression and
      signalling pathways. Nuclear localization of proteins is determined by their
      ability to interact with specific nuclear import and export factors. In the past
      year, substrate phosphorylation has emerged as a common mechanism for controlling
      this interaction.

PMID- 10209151
TI  - Bidirectional signaling between the cytoskeleton and integrins.
AB  - Clustering of integrins into focal adhesions and focal complexes is regulated by
      the actin cytoskeleton. In turn, actin dynamics are governed by Rho family
      GTPases. Integrin-mediated adhesion activates these GTPases, triggering assembly
      of filopodia, lamellipodia and stress fibers. In the past few years, signaling
      pathways have begun to be identified that promote focal adhesion disassembly and
      integrin dispersal. Many of these pathways result in decreased myosin-mediated
      cell contractility.

PMID- 10209152
TI  - Deciphering the pathways of life and death.
AB  - Caspase recruitment and oligomerization mediated by adaptor proteins constitute a
      basic mechanism of caspase activation. The complex phenotypes of the caspase
      knockout mice indicate that multiple mechanisms of caspase activation operate in
      parallel and that death signal transduction pathways are both cell-type and
      stimulus specific. The BH3-domain- containing pro-apototic members of Bcl-2
      family may be one of the critical links between the initial death signals and the
      central machinery of apoptosis.

PMID- 10209153
TI  - Apoptosis control by death and decoy receptors.
AB  - The death receptors Fas and tumor necrosis factor receptor 1 (TNFR1) trigger
      apoptosis upon engagement by their cognate death ligands. Recently, researchers
      have discovered several novel homologues of Fas and TNFR1: DR 3, 4, 5, and 6
      function as death receptors that signal apoptosis, whereas DcR 1, 2, and 3 act as
      decoys that compete with specific death receptors for ligand binding. Further,
      mouse gene knockout studies have enabled researchers to delineate some of the
      signaling pathways that connect death receptors to the cell's apoptotic
      machinery.

PMID- 10209154
TI  - Organization and regulation of mitogen-activated protein kinase signaling
      pathways.
AB  - Mitogen-activated protein kinases (MAPKs) are components of a three kinase
      regulatory cascade. There are multiple members of each component family of
      kinases in the MAPK module. Specificity of regulation is achieved by organization
      of MAPK modules, in part, by use of scaffolding and anchoring proteins. Scaffold
      proteins bring together specific kinases for selective activation, sequestration
      and localization of signaling complexes. The recent elucidation of scaffolding
      mechanisms for MAPK pathways has begun to solve the puzzle of how specificity in
      signaling can be achieved for each MAPK pathway in different cell types and in
      response to different stimuli. As new MAPK members are defined, determining their
      organization in kinase modules will be critical in understanding their select
      role in cellular regulation.

PMID- 10209155
TI  - Multiple positive and negative regulators of signaling by the EGF-receptor.
AB  - Signaling via the epidermal growth factor (EGF)-receptor family is subject to
      regulation and modulation by multiple ligands, effectors and negative regulators,
      as well as regulation by heterodimerization between family members and crosstalk
      between heterologous signaling pathways. Besides serving as a paradigm for
      receptor tyrosine kinases in general, this family is crucial for development and
      is often mutated or amplified in human tumors.

PMID- 10209156
TI  - Signalling through phosphoinositide 3-kinases: the lipids take centre stage.
AB  - Phosphoinositide 3-kinases (PI3Ks) phosphorylate inositol lipids at the 3'
      position of the inositol ring to generate the 3-phosphoinositides PI(3)P, PI(3,4)
      P2 and PI(3,4,5) P3. Recent research has shown that one way in which these lipids
      function in signal transduction and membrane trafficking is by interacting with 3
      phosphoinositide-binding modules in a broad variety of proteins. Specifically,
      certain FYVE domains bind PI(3)P whereas certain pleckstrin homology domains bind
      PI(3,4) P2 and/or PI(3,4,5) P3. Also in 1998, PTEN - a major tumour suppressor in
      human cancer - was also shown to antagonise PI3K signalling by removing the 3
      phosphate from 3-phosphoinositides.

PMID- 10209157
TI  - Multiple signals converging on NF-kappaB.
AB  - The recent identification of molecular components of the signal transduction
      pathway regulating activation of nuclear factor-kappaB (NF-kappaB) in response to
      cytokines such as tumor necrosis factor alpha and interleukin-1beta allows the
      evaluation of how other diverse stimuli impinge on the NF-kappaB activation
      pathway. These studies suggest a basis for specificity in activation of specific
      Rel-related family members and the genetic responses they promote.

PMID- 10209158
TI  - Regulation of LEF-1/TCF transcription factors by Wnt and other signals.
AB  - LEF-1/TCF transcription factors mediate a nuclear response to Wnt signals by
      interacting with beta-catenin. Wnt signaling and other cellular events that
      increase the stability of beta-catenin result in transcriptional activation by
      LEF-1/TCF proteins in association with beta-catenin. In the absence of Wnt
      signaling, LEF-1/TCF proteins repress transcription in association with Groucho
      and CBP. The LEF-1/TCF transcription factors can also interact with other
      cofactors and play an architectural role in the assembly of multiprotein enhancer
      complexes, which may allow for the integration of multiple signaling pathways.

PMID- 10209159
TI  - Costimulatory regulation of T cell function.
AB  - During the past several years, the critical role of costimulatory molecules in
      regulating T cell responses has been demonstrated. Costimulatory molecule CD28
      enhances whereas CTLA-4 downmodulates T cell responses. An understanding of the
      integration of the signals mediated by costimulatory molecules and the T cell
      receptor at the cellular and molecular levels is just beginning to be achieved.

PMID- 10209160
TI  - Regulating the onset of mitosis.
AB  - In eukaryotes, G2/M progression is mediated by activation of mitosis promoting
      factor (MPF). To ensure faithful chromosome segregation, the activity of key
      mitotic inducers and inhibitors are coupled with chromosome replication, spindle
      pole duplication, morphogenesis, and DNA damage. Evidence gathered in the past
      two years has underscored the importance of positioning MPF and its regulators in
      the proper place at the proper time to ensure orderly progression through the
      G2/M transition. Altering the spatial organization of G2/M regulators also
      contributes to prevention of mitosis following DNA damage.

PMID- 10209161
TI  - Organization and regulation of proteins at synapses.
AB  - The organization and regulation of synaptic connections in the mammalian nervous
      system entail complicated and co-ordinated molecular and cellular processes. The
      unveiling of various protein-protein interactions and their functional
      consequences at synapses have led to a greater understanding of the process of
      synapse formation and the modulation of synaptic transmission. Recent studies
      indicate that the major excitatory neurotransmitter receptors in the brain, the
      glutamate receptors, are associated with many different molecules that are
      involved in the formation of elaborate synaptic cytoskeletal networks and signal
      transduction cascades. These complex protein networks may play critical roles in
      the regulation of neurotransmitter receptor function and the efficacy of synaptic
      transmission.

PMID- 10209162
TI  - Secondary prevention after cerebral ischaemia of presumed arterial origin: is
      aspirin still the touchstone?

PMID- 10209163
TI  - Autosomal recessive Charcot-Marie-Tooth disease.

PMID- 10209164
TI  - Supratentorial cavernous haemangiomas and epilepsy: a review of the literature
      and case series.
AB  - OBJECTIVES: To characterise the clinical features and response to treatment of
      supratentorial cavernomas associated with epilepsy. METHODS: A systematic review
      of the literature was carried out and a retrospective case series of patients
      with cavernoma diagnosed by MRI and/or histology was compiled. Patient selection
      biases in the literature review were reduced as far as possible by selection of
      unbiased publications. RESULTS: In the literature, cavernomas were relatively
      less common in the frontal lobes. There were multiple cavernomas in 23% of cases.
      The main clinical manifestations were seizures (79%) and haemorrhage (16%). The
      annual haemorrhage rate was 0.7%. The outcome after excision was good with
      improvement in seizures in 92% of patients. In the case series the surgical
      outcome was less favourable, reflecting inclusion of a higher proportion of
      patients with intractable epilepsy. In both the literature review and the case
      series, outcome was poorer in cases with a longer duration of seizures at the
      time of surgery. CONCLUSIONS: The good surgical results, particularly in cases
      treated earlier, and the significant cumulative haemorrhage rate, suggest that
      excision is the optimum treatment. However, these factors have not been examined
      prospectively and, despite the availability of several retrospective studies, the
      optimum treatment, particularly for non-intractable cases, will only be
      determined by a prospective study.

PMID- 10209165
TI  - Study on the gene and phenotypic characterisation of autosomal recessive
      demyelinating motor and sensory neuropathy (Charcot-Marie-Tooth disease) with a
      gene locus on chromosome 5q23-q33.
AB  - OBJECTIVES: To report the occurrence of the autosomal recessive form of
      demyelinating Charcot-Marie-Tooth disease (CMT) with a locus on chromosome 5q23
      33 in six non-related European families, to refine gene mapping, and to define
      the disease phenotype. METHODS: In an Algerian patient with autosomal recessive
      demyelinating CMT mapped to chromosome 5q23-q33 the same unique nerve pathology
      was established as previously described in families with a special form of
      autosomal recessive demyelinating CMT. Subsequently, the DNA of patients with
      this phenotype was tested from five Dutch families and one Turkish family for the
      5q23-q33 locus. RESULTS: These patients and the Algerian families showed a
      similar and highly typical combination of clinical and morphological features,
      suggesting a common genetic defect. A complete cosegregation for markers D5S413,
      D5S434, D5S636, and D5S410 was found in the families. Haplotype construction
      located the gene to a 7 cM region between D5S643 and D5S670. In the present Dutch
      families linkage disequilibrium could be shown for various risk alleles and
      haplotypes indicating that most of these families may have inherited the
      underlying genetic defect form a common distant ancestor. CONCLUSIONS: This study
      refines the gene localisation of autosomal recessive demyelinating CMT, mapping
      to chromosome 5q23-33 and defines the phenotype characterised by a precocious and
      rapidly progressive scoliosis in combination with a relatively mild neuropathy
      and a unique pathology. Morphological alterations in Schwann cells of the
      myelinated and unmyelinated type suggest the involvement of a protein present in
      both Schwann cell types or an extracellular matrix protein rather than a myelin
      protein. The combination of pathological features possibly discerns autosomal
      recessive demyelinating CMT with a gene locus on chromosome 5q23-33 from other
      demyelinating forms of CMT disease.

PMID- 10209166
TI  - Successful treatment of IgM paraproteinaemic neuropathy with fludarabine.
AB  - OBJECTIVES: To evaluate the response of four patients with IgM paraproteinaemic
      neuropathy to a novel therapy-pulsed intravenous fludarabine. BACKGROUND: The
      peripheral neuropathy associated with IgM paraproteinaemia usually runs a
      chronic, slowly progressive course which may eventually cause severe disability.
      Treatment with conventional immunosuppressive regimens has been unsatisfactory.
      Fludarabine is a novel purine analogue which has recently been shown to be
      effective in low grade lymphoid malignancies. METHODS: Four patients were treated
      with IgM paraproteinaemic neuropathy with intravenous pulses of fludarabine. Two
      of the four patients had antibodies to MAG and characteristic widely spaced
      myelin on nerve biopsy and a third had characteristic widely spaced myelin only.
      The fourth had an endoneurial lymphocytic infiltrate on nerve biopsy and a
      diagnosis of Waldenstrom's macroglobulinaemia. RESULTS: In all cases subjective
      and objective clinical improvement occurred associated with a significant fall in
      the IgM paraprotein concentration in three cases. Neurophysiological parameters
      improved in the three patients examined. The treatment was well tolerated. All
      patients developed mild, reversible lymphopenia and 50% mild generalised
      myelosuppression, but there were no febrile episodes. CONCLUSION: Fludarabine
      should be considered as a possible treatment for patients with IgM MGUS
      paraproteinaemic neuropathy.

PMID- 10209167
TI  - Atypical form of amyotrophic lateral sclerosis.
AB  - OBJECTIVE: To investigate patients with an unusual type of muscular atrophy
      confined to the upper limbs (proximally dominant) and the shoulder girdle, while
      sparing the face and the legs until the terminal stage. METHODS: Eight patients
      (six men and two women) were clinically examined. The age at onset ranged from 42
      to 73 years, and the clinical course varied from 28 to 81 months. There was no
      family history of motor neuron disease in any of these patients. Necropsy was
      performed in two of them. RESULTS: All eight patients basically showed a similar
      distribution of muscular weakness and atrophy. Subluxation of the shoulder joints
      was found in all patients. Reflexes were absent in the upper limbs in all
      patients, but were almost normal in the face and legs in most patients.
      Pathological reflexes could be elicited in only one patient. Electromyography
      showed typical neurogenic changes in the limbs of all patients. Cervical MRI
      disclosed moderate spondylotic changes in seven patients. Antiganglioside
      antibodies were negative in six patients tested. Abnormal trinucleotide (CAG)
      repeat expansion of androgen receptor gene was not recognised in five patients
      examined. Bulbar involvement developed in three patients during the course of the
      disease. At necropsy, one patient showed degeneration of the pyramidal tracts and
      motor cortex including Betz cells as well as loss of spinal anterior horn cells
      and brainstem motor neurons, which is consistent with ALS; in another patient
      there was neuronal loss of anterior horn cells at the spinal cord accompanied by
      astrogliosis, whereas the motor cortex and brainstem motor nuclei were relatively
      well preserved. Intracytoplasmic inclusions such as Bunina bodies, skein-like
      inclusions, and Lewy body-like inclusions were found in both patients.
      CONCLUSION: These patients with their peculiar pattern of muscular atrophy seem
      to have ALS or a subtype of ALS.

PMID- 10209168
TI  - Motor root conduction in neuralgic amyotrophy: evidence of proximal conduction
      block.
AB  - OBJECTIVE: To determine the presence and role of proximal conduction block in
      neuralgic amyotrophy. METHODS: Percutaneous electrical stimulation of cervical
      roots and brachial plexus was employed in eight patients with neuralgic
      amyotrophy. Root to Erb's point compound muscle action potential amplitude ratios
      for abductor digiti minimi, extensor digitorum communis, biceps, and deltoid
      muscles were compared with results obtained from 10 healthy controls. RESULTS:
      Conduction block in the nerve to one muscle was found in three of eight patients
      (38%) suggesting focal proximal demyelination. Repeat studies showed axonal
      degeneration, resolution, and persistence of conduction block in these three
      patients respectively. CONCLUSION: Focal conduction block plays a significant
      part in the pathogenesis of neuralgic amyotrophy, which is generally regarded as
      an axon loss process. Therapeutic intervention should be directed to patients
      with persistent conduction block, with the aim of eradicating the block and
      possibly minimising subsequent axon loss.

PMID- 10209169
TI  - Intraoperative monitoring during surgery for acoustic neuroma: benefits of an
      extratympanic intrameatal electrode.
AB  - OBJECTIVES: To assess the utility of an extratympanic intrameatal electrode for
      intraoperative monitoring during acoustic neuroma and other cerebellopontine
      angle tumour surgery and to define the neurophysiological and surgical factors
      which influence hearing preservation. METHODS: Twenty two patients, 18 with
      acoustic neuromas and four with other cerebellopontine angle tumours, underwent
      intraoperative monitoring during tumour excision. The extratympanic intrameatal
      electrode (IME) was used to record the electrocochleogram (ECoG) and surface
      electrodes to record the brainstem auditory evoked response (ABR). RESULTS: The
      compound action potential (CAP) of the ECoG was two and a half times greater in
      amplitude than wave I of the ABR and was easily monitored. Virtually instant
      information was available as minimal averaging was required. Continuous
      monitoring was possible from the commencement of anaesthesia to skin closure. The
      IME was easy to place, non-invasive, and did not interfere with the operative
      field. Operative procedures which affected CAP or wave V latency or amplitude
      were drilling around the internal auditory meatus, tumour dissection, nerve
      section, and brainstem and cerebellar retraction. Hearing was achieved in 59% of
      patients. CONCLUSIONS: The IME had significant benefits in comparison with other
      methods of monitoring. The technique provided information beneficial to
      preservation of hearing.

PMID- 10209170
TI  - Predicting deterioration in patients with lobar haemorrhages.
AB  - OBJECTIVE: To study the clinical course and determine predictors of deterioration
      in patients with lobar haemorrhages). METHODS: A comprehensive review of 61
      consecutive patients with lobar haemorrhages was performed. Neurological
      deterioration was defined as (1) decrease in Glasgow coma sum score by 2 points,
      (2) new neurological deficit, or (3) clinical signs of brain herniation. A
      univariate logistic regression was performed and expressed in odds ratios.
      RESULTS: Sixteen of 61 (26%) patients with lobar haemorrhages deteriorated after
      admission. In a univariate analysis, only a Glasgow coma score <14 predicted
      deterioration (75% of deteriorators v 24% who did not deteriorate; p<0.0001).
      Initial CT characteristics predictive of deterioration included haemorrhage
      volume >60 ml (63% v 16%, p< 0.0001), shift of the septum pellucidum (75% v 36%,
      p<0.01), effacement of the contralateral ambient cistern (33% v 0%, p<0.0001),
      and widening of the contralateral temporal horn (50% v 0%, p<0.0001). Patients
      presenting and deteriorating within 12 hours of ictus declined due to enlargement
      of the haemorrhage. Those who deteriorated more than 12 hours after initial
      neurological symptoms, showed increased mass effect secondary to oedema.
      CONCLUSION-Patients with lobar haemorrhages presenting immediately after ictus
      are at risk for deterioration from enlargement of the haemorrhage and predictors
      of deterioration may be absent. Patients with large volume lobar haemorrhages
      presenting to the emergency department with decreased level of consciousness and
      shift on CT are at risk for further deterioration from worsening oedema. These
      patients require close observation and early aggressive management may be
      warranted.

PMID- 10209171
TI  - Critical closing pressure in cerebrovascular circulation.
AB  - OBJECTIVE: Cerebral critical closing pressure (CCP) has been defined as an
      arterial pressure threshold below which arterial vessels collapse. Hypothetically
      this is equal to intracranial pressure (ICP) plus the contribution from the
      active tone of cerebral arterial smooth muscle. The correlation of CCP with ICP,
      cerebral autoregulation, and other clinical and haemodynamic modalities in
      patients with head injury was evaluated. METHOD: intracranial pressure, arterial
      blood pressure (ABP) and middle cerebral artery blood flow velocity were recorded
      daily in ventilated patients. Waveforms were processed to calculate CCP, the
      transcranial Doppler-derived cerebral autoregulation index (Mx), mean arterial
      pressure (ABP), intracranial pressure (ICP), and cerebral perfusion pressure
      (CPP). RESULTS: Critical closing pressure reflected the time related changes in
      ICP during plateau and B waves. Overall correlation between CCP and ICP was mild
      but significant (R=0.41; p<0.0002). The mean difference between ABP and CCP
      correlated with CPP (R=0.57, 95% confidence interval (95% CI) for prediction 25
      mm Hg). The difference between CCP and ICP, described previously as proportional
      to arterial wall tension, correlated with the index of cerebral autoregulation Mx
      (p<0.0002) and CPP (p<0.0001). However, by contrast with the Mx index, CCP-ICP
      was not significantly correlated with outcome after head injury. CONCLUSION:
      Critical closing pressure, although sensitive to variations in ICP and CPP,
      cannot be used as an accurate estimator of these modalities with acceptable
      confidence intervals. The difference CCP-ICP significantly correlates with
      cerebral autoregulation, but it lacks the power to predict outcome after head
      injury.

PMID- 10209172
TI  - Comparison of mouse bioassay and immunoprecipitation assay for botulinum toxin
      antibodies.
AB  - OBJECTIVE: To compare a recently developed immunoprecipitation assay (IPA) to the
      mouse protection bioassay (MPB), currently considered the "gold standard", for
      detecting antibodies against botulinum toxin A (BTX-A) and to correlate these
      assay results with clinical responses to BTX-A injections. METHODS: MPB and IPA
      assays were performed on serum samples from 83 patients (38 non-responders, 45
      responders) who received BTX-A injections. Six non-responders had serum tested on
      two separate occasions. Some patients also received a "test" injection into
      either the right eyebrow (n=29) or right frontalis (n=19). RESULTS: All patients
      antibody positive (Ab+) by MPB were also Ab+ by IPA, whereas an additional 19
      patients (17 with reduced or no clinical response) who were MPB Ab- were Ab+,
      with low titres, by IPA. Two of these 19 patients (non-responders) were initially
      MPB Ab- but later became MPB Ab+. Similar to previous studies, the sensitivity
      for the MPB was low; 50% for clinical, 38% for eyebrow, and 30% for frontalis
      responses whereas the IPA sensitivity was much higher at 84% for clinical
      (p<0.001), 77% for eyebrow (p=0.111, NS) and 90% for frontalis responses
      (p<0.02). The IPA specificity was 89% for clinical, 81% for eyebrow, and 89% for
      frontalis responses, whereas the MPB specificity was 100% for all three response
      types, which were all non-significant differences. CONCLUSIONS: Both assays had
      high specificity although the sensitivity of the IPA was higher than the MPB. In
      addition, the IPA seems to display positivity earlier than the MPB, and as such,
      it may prognosticate future non-responsiveness. Eyebrow and frontalis "test"
      injections correlated well with clinical and immunological results and are useful
      in the assessment of BTX non-responders.

PMID- 10209173
TI  - Non-painful sensory phenomena after spinal cord injury.
AB  - OBJECTIVES: Non-painful sensory phenomena or "phantom" sensations are common
      after spinal cord injury. However, the physiological mechanisms responsible for
      these sensations are poorly understood. The aim of this study, therefore, was to
      document in a prospective fashion the time course, prevalence, and features of
      non-painful sensory phenomena after spinal cord injury, and to determine whether
      there was a relation between the presence of these sensations and completeness,
      level of injury, and type of spinal cord injury. METHODS: Patients admitted to an
      acute spinal injuries unit were interviewed after admission and at several time
      points over a 2 year period to determine the presence and characteristics of non
      painful sensations. Sensations were divided into simple and complex, with complex
      referring to sensations that incorporated a sensation of volume, length, posture,
      or movement. RESULTS: The present study showed that the large majority (90%) of
      patients experience either type of sensation and most complex sensations (60%)
      are first experienced within 24 hours after the injury. Complex sensations were
      more common in those patients who had complete spinal cord injuries. The presence
      of either type of sensation did not seem to be related to the level of injury or
      the type of injury (cord syndrome). A relatively small proportion (22%) of
      patients reported that the postural sensations were related to their position at
      the time of injury and sensations were more commonly related to a familiar,
      comfortable, or often used position before the spinal cord injury. CONCLUSION:
      Complex sensations such as postural illusions seem to be due to functional
      changes in the CNS that may occur almost immediately after spinal cord injury.
      These sensations may be related to a strong sensory memory "imprint" that has
      been established before injury.

PMID- 10209174
TI  - Recurrent spinal epidural metastases: a prospective study with a complete follow
      up.
AB  - OBJECTIVES: Prospective studies with a complete follow up in patients with spinal
      epidural metastases (SEM) are rare, so little is known of the incidence and
      relevance of recurrent spinal epidural metastases (RSEM). This prospective study
      was undertaken as a part of a previously started and extended prospective study
      to determine the occurrence and details of RSEM. METHODS: Patients with SEM of
      various primary malignancies were followed up until death. The diagnosis was
      confirmed after neurological examination by imaging studies visualising not only
      the clinically suspected level, but also as much of the spinal canal as possible.
      RESULTS: Recurrent spinal epidural metastases (RSEM) occurred in 21 of the 103
      patients (20%) after a median interval of 7 months and, after treatment, a second
      recurrence occurred in 11 patients (11%), a third recurrence in two patients
      (2%), and a sixth recurrence in one patient (1%). RSEM developed about as often
      at the initial level (55%) as at a different level (45%), did not occur more
      often in patients with initially multiple SEM, but, not surprisingly, occurred
      much more often in patients with longer survival. About one half of the patients
      surviving 2 years, and nearly all patients surviving 3 years or longer developed
      RSEM. Ambulatory state could be preserved in most patients, even after their
      second recurrence. CONCLUSION: RSEM are common and even several episodes of RSEM
      in the same patient are not rare. Patients with SEM who survive long enough have
      a high risk of RSEM and prompt treatment of RSEM to maintain the ambulatory state
      of the patient is valuable.

PMID- 10209175
TI  - Volumetric magnetic resonance imaging study of the brain in subjects with sex
      chromosome aneuploidies.
AB  - OBJECTIVES: Cognitive impairment has been reported in people with sex chromosome
      aneuploides (SCAs) and it has been proposed that the presence of an extra sex
      chromosome may have an adverse effect on neurodevelopment. This study examines
      the hypothesis with structural MRI of the brain. METHODS: Thirty two subjects
      with SCA (XXX (n=12), XYY (n=10), and XXY (n=10)) from a birth cohort study were
      matched groupwise for age, parental social class, and height with normal controls
      (13 female, 26 male). Brain MRI, measurements of IQ, and a structured psychiatric
      interview were performed. RESULTS: The XXX females and XXY males had
      significantly smaller whole brain volumes than controls of the same phenotypic
      sex (p=0.003 and p</=0.05 respectively). The XXY group also had bilaterally
      enlarged lateral ventricles (p</=0.05). No significant differences were found
      between the XYY group and controls. IQ scores in all SCA groups were lower than
      in the control groups. CONCLUSIONS: The main result of reduced brain volumes in
      XXX and XXY subjects, but not in XYY subjects, indicates that the presence of a
      supernumerary X chromosome has a demonstrable effect on brain development.

PMID- 10209176
TI  - Bilateral enhancing thalamic lesions in a 10 year old boy: case report.
AB  - A young boy presented with monoparesis of the left arm. MRI disclosed bilateral
      enhancing thalamic lesions. Biopsy results and subsequent clinical history were
      most compatible with postinfectious or acute disseminated encephalomyelitis. This
      represents one of the first cases of acute disseminated encephalomyelitis
      affecting the thalami, established by biopsy. This uncommon disease entity is
      reviewed and how it may affect the deep grey matter is described.

PMID- 10209177
TI  - Mortality in patients with epilepsy: 40 years of follow up in a Dutch cohort
      study.
AB  - To investigate the extent of and the causes of excess mortality in patients with
      epilepsy, mortality was studied in a cohort of patients with newly diagnosed
      epilepsy over an extended follow up period. All patients (both inpatients and
      outpatients) of the Instituut voor Epilepsiebestrijding in Heemstede, the
      Netherlands between 1953 and 1967 were included in the study. Complete follow up
      was obtained for 1355 patients, 746 men and 609 women. The mean follow up was 28
      years (range 6 months-41 years). In total, 38 665 person years were surveyed, in
      which 404 patients died. All cause mortality was threefold increased (risk ratio
      (RR) 3.2; 95%CI 2.9-3. 5), and was only slightly higher for men than for women.
      Mortality was highest under 20 years of age (RR 7.6; 95%CI 6.5-8.7), and during
      the first 2 years of follow up (RR 16; 95%CI 12-20). Mortality directly related
      to epilepsy accounted for 18 of the 53 deaths in the first 2 years after
      diagnosis, which is equivalent to an incidence rate of 6.8 per 1000 person-years
      (95% CI 4.1-10). After 2 years 110 of the 351 deaths could be attributed to
      epilepsy itself, or were epilepsy related, with an incidence rate of 3.1 per 1000
      person-years (95% CI 2.5-3.6). The data presented suggest that the increased
      mortality risk in patients with epilepsy is attributable in part to epilepsy
      itself, and is predominantly present at younger age and early after diagnosis.
      However, the absolute risk is moderate.

PMID- 10209178
TI  - Microangiopathy of the brain and retina with hearing loss in a 50 year old woman:
      extending the spectrum of Susac's syndrome.
AB  - A 50 year old woman presented with a subacute onset of vertigo and diplopia
      followed by an encephalopathy with confusion, spasticity, ataxia, myoclonus, and
      multiple branch retinal arteriolar occlusions and unilateral sensorineural
      deafness. Brain biopsy confirmed multiple microinfarcts with no vasculitis. After
      the procedure she had a right iliofemoral deep vein thrombosis and was found to
      be heterozygous for the factor V Leiden mutation. She was treated with
      anticoagulants and made a marked recovery with no relapses 6 months after
      presentation. This case extends the age range at which Susac's syndrome can
      present, and raises the possibility that the condition may be associated with
      abnormalities of coagulation.

PMID- 10209179
TI  - Operated low grade astrocytomas: a long term PET study on the effect of
      radiotherapy.
AB  - The role of postoperative radiotherapy in patients with low grade gliomas is not
      established yet. PET with 11C methionine (MET) and 18F fluorodeoxyglucose (FDG)
      was used to perform cross sectional comparisons as well as within patient follow
      up studies in 30 operated patients with fibrillary astrocytoma WHO II. Uptake of
      tracer by tumour was quantified by radioactivity concentration ratios in tumour
      over contralateral brain (T/C). Comparing patients who did (n=13) or did not
      (n=17) receive external radiotherapy subsequent to first tumour resection, no
      differences in MET and FDG T/C between both groups were found during a
      postoperative period of 94 months (when recurrence and malignant progression of
      low grade astrocytomas are expected). Malignant progression occurred at a similar
      rate in both patient groups at a mean (SD) postoperative interval of 46 (26)
      months. Irrespective of whether radiotherapy was applied or not, malignant tumour
      recurrences showed higher T/C values (MET: 1.70 (0.64), FDG: 0.98 (0.23)) than
      recurrences without signs of malignancy (MET: 1.21 (0.21), FDG: 0.82 (0.08))
      (Mann-Whitney: MET p=0.086, FDG p=0.035). The data show a relative lack of
      radiotherapy administered immediately after first tumour resection. In the course
      of disease, patients with tumours undergoing malignant progression may be
      identified with PET tracer methods.

PMID- 10209180
TI  - Effect of radiotherapy on brain glucose metabolism in patients operated on for
      low grade astrocytoma.
AB  - OBJECTIVE: To assess the effect of postoperative radiotherapy on brain glucose
      metabolism (CMRGlu) of operated patients with low grade astrocytomas. METHODS:
      PET and 18F-fluorodeoxyglucose was used to measure absolute CMRGlu in patients
      with fibrillary astrocytoma (WHO II) of the frontal lobe, who did (n=7) or did
      not (n=12) receive radiotherapy subsequent to first debulking tumour resection.
      In addition, statistical parametric mapping (SPM95) was applied to assess the
      pattern of relative CMRGlu associated with the frontal tumour. Data were compared
      with 12 healthy controls. RESULTS: A global reduction of absolute CMRGlu was
      found when either patients with or without radiotherapy were compared with
      controls (ROI analysis). Brain areas of relative CMRGlu reduction were found in
      the brain ipsilateral and contralateral to the tumour, comparing both patient
      groups with controls by SPM ("tumour diaschisis effect"). Superimposed, absolute
      CMRGlu in the contralateral frontal, parietal, occipital cortex as well as in the
      white matter was on average 17% lower in patients receiving radiotherapy than in
      patients who did not. CONCLUSIONS: The data discriminate a tumour effect from a
      radiotherapy effect, and support the view of adverse effects of radiotherapy on
      brain not directly involved by tumour.

PMID- 10209181
TI  - Human chorionic gonadotrophin in CSF, not serum, predicts outcome in germinoma.
AB  - OBJECTIVES: Some intracranial germinomas, which may contain syncytiotrophoblastic
      giant cells (STGCs), are associated with a mildly to moderately increased human
      chorionic gonadotropin (HCG) concentration in serum, and patients with such
      germinomas are thus treated more aggressively than those with "pure" germinoma.
      However, the patients with germinoma and detectable HCG in CSF but not in serum
      have been classified and treated similarly to those with "pure" germinomas. The
      outcome of these patients and the relevance of HCG in the CSF were analysed.
      METHODS: The outcomes of patients with germinoma and increased serum HCG
      concentration (n=7) were compared with those of patients having detectable HCG
      titre in the CSF but not in the serum (n=5). RESULTS: Both groups in our series
      received similar treatments and also showed similar recurrence rates. The 40%
      recurrence rate in the group with HCG only in CSF did not correspond to the rate
      typical for "pure" germinoma: these tumours would be expected to have a better
      outcome. An additional patient whose CSF HCG were raised without increased serum
      HCG at recurrence is presented. CONCLUSIONS: It is recommended that patients with
      an increased HCG concentration in CSF should be considered to have "HCG producing
      germinoma", and they should be treated and followed up accordingly.

PMID- 10209182
TI  - Vasculitic polyradiculopathy in systemic lupus erythematosus.
AB  - A 22 year old woman with recently diagnosed systemic lupus erythematosus
      presented with subacute progressive areflexic paraparesis, electrophysiologically
      identified as a pure axonal polyradiculopathy. Sural nerve biopsy disclosed
      necrotising vasculitis. A striking radiological feature was marked enhancement of
      the cauda equina with gadolinium.

PMID- 10209183
TI  - Neurological complications of anterior spinal surgery for kyphosis with normal
      somatosensory evoked potentials (SEPs).
AB  - We report a case of neurological complications of anterior release for correction
      of kyphosis. After the operation, the patient had pyramidal weakness and
      decreased pain sensation below T5, whereas light touch, proprioception and
      vibration sensation were intact. Clinical and neurophysiological findings in this
      patient suggested a partial lesion of the spinal cord probably due to ischaemia
      in the territory of the anterior spinal artery. Intraoperative and postoperative
      tibial nerve SEPs remained normal, which stresses the need for recording from the
      motor pathways.

PMID- 10209184
TI  - The tau gene A0 polymorphism in progressive supranuclear palsy and related
      neurodegenerative diseases.
AB  - Progressive supranuclear palsy is characterised pathologically by the deposition
      of neurofibrillary tangles consisting of tau protein. Patients with the disease
      have been reported to have a more frequent occurrence of one allele of an
      intronic polymorphism of the tau gene. Other diseases which may involve tau
      deposition include frontotemporal dementia and corticobasal degeneration. This
      polymorphism has been studied in a series of subjects with progressive
      supranuclear palsy, corticobasal degeneration, frontotemporal dementia,
      idiopathic Parkinson's disease, and normal controls to (1) confirm this
      association in a large series and (2) to investigate a possible role for this
      association in other disorders which involve tau deposition. The results confirm
      the finding of an overrepresentation of the A0 allele and the A0/A0 genotype in
      patients with progressive supranuclear palsy, in the largest series reported to
      date. The A0 allele was found in 91% of patients with progressive supranuclear
      palsy as opposed to 73% of controls (p<0.001) and the A0/A0 genotype was seen in
      84% of patients as compared with 53% of controls (p<0.01). There was no
      significant difference between patients with Parkinson's disease, frontotemporal
      dementia, or corticobasal degeneration, and controls. The A0 allele may have a
      direct effect on tau isoform expression in progressive supranuclear palsy or it
      may be in linkage disequilibrium with an adjacent determinant of tau gene
      expression. The explanation for this difference between a predisposition factor
      to progressive supranuclear palsy and the other conditions may lie in the
      molecular pathology of these diseases.

PMID- 10209185
TI  - Concurrent performance of motor tasks and processing capacity in patients with
      schizophrenia.
AB  - Any task is carried out more successfully if we allocate undivided attention to
      it, but as demands on attentional capacity increase-for example, in concurrent or
      dual task conditions-performance on attended tasks becomes more impaired.
      Patients with schizophrenia show impaired performance on tasks requiring high
      levels of attentional capacity. This study examines performance of 11 patients
      with schizophrenia and 13 normal controls on two motor tasks (placing pegs in a
      pegboard and repetitive index finger tapping) under unimanual, bimanual, and dual
      task conditions. The patients with schizophrenia placed fewer pegs and had
      reduced tapping speed in unimanual and bimanual conditions. However, the
      decrement in bimanual performance as a percentage of unimanual performance was
      not significantly different for the patients and controls on either the pegboard
      or tapping tasks. By contrast, under dual task conditions, the performance of the
      patients with schizophrenia in peg placement actually improved relative to the
      unimanual pegboard task, whereas tapping performance deteriorated compared with
      the unimanual tapping, a decrement that was significantly greater for the
      patients. Thus the improvement in the visually guided pegboard task was at the
      expense of the repetitive tapping task. These results are discussed in terms of
      an impairment of self initiated movement with general sparing of externally
      triggered movements in schizophrenia and the role of frontostriatal loops in this
      process.

PMID- 10209186
TI  - Sympathetic contralateral vestibulopathy after unilateral zoster oticus.
AB  - A unique case of initially right sided varicella zoster induced Ramsay-Hunt
      syndrome with complete vestibular loss is reported. The patient subsequently
      developed deficits of the left vestibule 5 months later. An autoimmune
      pathogenesis of the left vestibular failure rather than bilateral varicella
      zoster infection was suggested by the following data: (1) no evidence of
      vesicular eruptions on the left auricle and the virtual absence of antiviral
      antibodies after onset of bilateral vestibulopathy; (2) prompt response of the
      left vestibule to immunosuppressive therapy with corticosteroids; and (3)
      presence of atypical nervous tissue specific autoantibodies against a 45 kDa
      protein.

PMID- 10209187
TI  - Chronic inflammatory demyelinating polyradiculoneuropathy: a prevalence study in
      south east England.
AB  - Although there are now widely accepted diagnostic criteria for chronic
      inflammatory demyelinating polyradiculoneuropathy (CIDP) there are few
      epidemiological data. A prevalence study was performed in the four Thames health
      regions, population 14 049 850. The prevalence date was 1 January 1995. Data were
      from a national consultant neurologist surveillance programme and the personal
      case series of two investigators. A diagnosis of CIDP was made according to
      definite, probable, possible, or suggestive diagnostic criteria. A wide
      difference in prevalence rates between the four health regions was noted,
      probably due to reporting bias. In the South East Thames Region, from which the
      data were most comprehensive the prevalence for definite and probable cases was
      1.00/100 000; the highest total prevalence (if possible and suggestive cases were
      included) would have been 1.24/100 000. On the prevalence date 13% of patients
      required aid to walk and 54% were still receiving treatment.

PMID- 10209188
TI  - Alexander Onufrievich Kovalevsky (1840-1901).

PMID- 10209189
TI  - Levodopa may improve orthostatic tremor: case report and trial of treatment.
AB  - Primary orthostatic tremor is a regular fast lower limb tremor causing
      unsteadiness on standing. Treatment is generally unsatisfactory. A patient with
      primary orthostatic tremor who 9 years later developed levodopa responsive
      idiopathic Parkinson's disease is described. The patient exhibited the classic
      features of primary orthostatic tremor with relief of the tremor by walking or
      sitting while treated with levodopa. However, in the "off" state, when the
      benefits of levodopa disappeared, this orthostatic tremor was continuous and
      severely compromised the patient's gait. On the basis of this finding eight
      patients with primary orthostatic tremor were treated with levodopa. Five
      patients experienced benefit and elected to remain on long term treatment. This
      study is the first trial of therapy in primary orthostatic tremor and suggests
      that levodopa can lead to good symptomatic relief in this potentially disabling
      condition.

PMID- 10209190
TI  - Visual hallucinations and palinopsia due to an occipital lobe tuberculoma.

PMID- 10209191
TI  - Cortical sclerosis presenting with dementia as a sequel of rapid correction of
      hyponatraemia.

PMID- 10209192
TI  - Paradoxical emboli: the proof was short lived.

PMID- 10209194
TI  - Management of stroke: A practical guide for the prevention, evaluation and
      treatment of acute stroke 

PMID- 10209193
TI  - Greenfield's neuropathology. Sixth edition 

PMID- 10209195
TI  - Disorders of the brain and mind 

PMID- 10209196
TI  - Identification of a novel gene product preferentially expressed in rat lens
      epithelial cells.
AB  - PURPOSE: We searched for an mRNA that is differentially expressed in rat lens
      epithelial and fiber cells to use as a marker for differentiation. METHODS: An
      mRNA differential display method was used to identify genes with altered
      expression during differentiation of lens epithelial cells. RESULTS: One gene
      (partial sequence) was identified and confirmed to be expressed preferentially in
      undifferentiated rat lens epithelial cells. Among non-lens tissues, a trace
      amount was detected in cornea, but not in retina or eleven non-ocular tissues
      tested. This cloned partial gene sequence (322 base pairs) is at least 93%
      identical to overlapping rat and mouse EST sequences, and extends the sequence of
      both ESTs at the 5' end. CONCLUSIONS: A clone has been isolated that is
      preferentially expressed in lens epithelial cells. Expression of this gene was
      down-regulated when rat pup lens epithelial cell explants were induced to
      differentiate. The unusual pattern of expression suggests a novel function for
      this gene.

PMID- 10209197
TI  - The golden age of retinal cell culture.
AB  - In the late 1950s, the study of retinal cells in vitro was in its infancy. Today,
      retinal cell and tissue culture is routinely used for studies of cell growth,
      differentiation, cytotoxicity, gene expression, and cell death. This review
      discusses the major classifications of retinal cell and tissue culture, including
      primary cell/explant models, retinoblastoma cell lines, and genetically
      engineered cell lines. These topics are addressed in an historical perspective,
      coupled with present-day applications for this continually-developing technology.

PMID- 10209199
TI  - Roundtable Participants.

PMID- 10209200
TI  - Early Stages of Renal Disease.

PMID- 10209202
TI  - Interventions and Outcomes at Selected Managed Care Organizations.

PMID- 10209201
TI  - Outcome Measures in Patients With ESRD.

PMID- 10209203
TI  - Discussion.

PMID- 10209206
TI  - Membrane interactions of the synthetic N-terminal peptide of HIV-1 gp41 and its
      structural analogs.
AB  - Structural and functional studies assessed the membrane actions of the N terminus
      of HIV-1 glycoprotein 41000 (gp41). Earlier site-directed mutagenesis has shown
      that key amino acid changes in this gp41 domain inhibit viral infection and
      syncytia formation. Here, a synthetic peptide corresponding to the N terminus of
      gp41 (FP; 23 residues, 519-541), and also FP analogs (FP520V/E with Val-->Glu at
      residue 520; FP527L/R with Leu-->Arg at 527; FP529F/Y with Phe-->Tyr at 529; and
      FPCLP1 with FP truncated at 525) incorporating these modifications were prepared.
      When added to human erythrocytes at physiologic pH, the lytic and aggregating
      activities of the FP analogs were much reduced over those with the wild-type FP.
      With resealed human erythrocyte ghosts, the lipid-mixing activities of the FP
      analogs were also substantially depressed over that with the wild-type FP.
      Combined with results from earlier studies, theoretical calculations using
      hydrophobic moment plot analysis and physical experiments using circular
      dichroism and Fourier transform infrared spectroscopy indicate that the
      diminished lysis and fusion noted for FP analogs may be due to altered peptide
      membrane lipid interactions. These data confirm that the N-terminal gp41 domain
      plays critical roles in the cytolysis and fusion underlying HIV-cell infection.

PMID- 10209207
TI  - C1q binding to liposomes is surface charge dependent and is inhibited by peptides
      consisting of residues 14-26 of the human C1qA chain in a sequence independent
      manner.
AB  - Complement activation by anionic liposomes proceeds by antibody-independent, C1q
      initiated activation of the classical pathway. Purified C1q bound to anionic
      liposomes in an acidic lipid concentration-dependent manner. Saturation binding,
      but not the apparent association constant, was enhanced by increasing the
      cardiolipin content of the liposomes or decreasing either the pH or ionic
      strength of the reaction mixture. These observations indicate the involvement of
      electrostatic factors in the binding. A highly cationic region in the collagen
      like domain of C1q comprised of residues 14-26 of the C1qA polypeptide chain was
      assessed for involvement in liposome binding. This region has previously been
      shown to mediate C1q binding to other immunoglobulin-independent activators of
      the classical pathway of complement. Peptides containing residues 14-26 of C1qA,
      denoted C1qA14-26, inhibited C1q binding to and complement activation by anionic
      liposomes. The inhibitory capacity of these cationic peptides had no sequence or
      conformation specificity. Rather, the amount of positive charge on the peptides
      was the determining factor. When present in excess, peptides with five cationic
      residues inhibited C1q binding and complement activation; however, C1q peptides
      with only two cationic residues did not. In addition to the C1qA14-26 region,
      other parts of C1q that contain cationic residues may also be involved in C1q
      binding to anionic liposomes.

PMID- 10209208
TI  - Modulation of Ca2+-dependent anion secretion by protein kinase C in normal and
      cystic fibrosis pancreatic duct cells.
AB  - The study investigated the role of protein kinase C (PKC) in the modulation of
      agonist-induced Ca2+-dependent anion secretion by pancreatic duct cells. The
      short-circuit current (ISC) technique was used to examine the effect of PKC
      activation and inhibition on subsequent ATP, angiotensin II and ionomycin
      activated anion secretion by normal (CAPAN-1) and cystic fibrosis (CFPAC-1)
      pancreatic duct cells. The ISC responses induced by the Ca2+-mobilizing agents,
      which had been previously shown to be attributed to anion secretion, were
      enhanced in both CAPAN-1 and CFPAC-1 cells by PKC inhibitors, staurosporine,
      calphostin C or chelerythrine. On the contrary, a PKC activator, phorbol 12
      myristate 13-acetate (PMA), was found to suppress the agonist-induced ISC in
      CFPAC-1 cells and the ionomycin-induced ISC in CAPAN-1 cells. An inactive form of
      PMA, 4alphad-phorbol 12, 13-didecanote (4alphaD), was found to exert
      insignificant effect on the agonist-induced ISC, indicating a specific effect of
      PMA. Our data suggest a role of PKC in modulating agonist-induced Ca2+-dependent
      anion secretion by pancreatic duct cells. Therapeutic strategy to augment Ca2+
      activated anion secretion by cystic fibrosis pancreatic duct cells may be
      achieved by inhibition or down-regulation of PKC.

PMID- 10209209
TI  - The effect of hypericin and hypocrellin-A on lipid membranes and membrane
      potential of 3T3 fibroblasts.
AB  - Hypericin (HY) and Hypocrellin-A (HA) photosensitization induce rapid
      depolarization of plasma membrane in 3T3 cells as revealed by confocal
      microspectrofluorimetry using diO-C5(3) fluorescent probe. HY and HA are also
      able to rigidify the lipid membrane of DMPC liposomes as indicated by the
      decrease of pyrene excimer fluorescence used as a marker of the lipid membrane
      fluidity. We have also observed a nonspecific inhibition of Na+,K+-ATPase
      activity due to the HY and HA photosensitization. The described effects are
      concentration- and light dose-dependent and generally more pronounced for HA than
      for HY. All these observations suggest that the lipid membranes can play an
      important role in the photosensitization process induced by HY and HA at the
      cellular level. It can be hypothesized that for HA and HY the secondary mechanism
      following type I or type II photosensitization process can be the peroxidation of
      membrane lipids as well, and thus intracellular membranes seem to be one of the
      most important targets of these photosensitizers.

PMID- 10209210
TI  - Regulation of Ca2+ transport by sarcoplasmic reticulum Ca2+-ATPase at limiting
      [Ca2+].
AB  - The factors regulating Ca2+ transport by isolated sarcoplasmic reticulum (SR)
      vesicles have been studied using the fluorescent indicator Fluo-3 to monitor
      extravesicular free [Ca2+]. ATP, in the presence of 5 mM oxalate, which clamps
      intravesicular [Ca2+] at approximately 10 microM, induced a rapid decline in Fluo
      3 fluorescence to reach a limiting steady state level. This corresponds to a
      residual medium [Ca2+] of 100 to 200 nM, and has been defined as [Ca2+]lim,
      whilst thermodynamic considerations predict a level of less than 1 nM. This value
      is similar to that measured in intact muscle with Ca2+ fluophores, where it is
      presumed that sarcoplasmic free [Ca2+] is a balance between pump and leaks.
      Fluorescence of Fluo-3 at [Ca2+]lim was decreased 70% to 80% by histidine,
      imidazole and cysteine. The K0.5 value for histidine was 3 mM, suggesting that
      residual [Ca2+]lim fluorescence is due to Zn2+. The level of Zn2+ in preparations
      of SR vesicles, measured by atomic absorption, was 0.47+/-0.04 nmol/mg,
      corresponding to 0.1 mol per mol Ca-ATPase. This is in agreement with findings of
      Papp et al. (Arch. Biochem. Biophys., 243 (1985) 254-263). Histidine, 20 mM,
      included in the buffer, gave a corrected value for [Ca2+]lim of 49+/-1.8 nM,
      which is still higher than predicted on thermodynamic grounds. A possible
      'pump/leak' mechanism was tested by the effects of varying active Ca2+ transport
      1 to 2 orders with temperature and pH. [Ca2+]lim remained relatively constant
      under these conditions. Alternate substrates acetyl phosphate and p-NPP gave
      similar [Ca2+]lim levels even though the latter substrate supported transport 500
      fold slower than with ATP. In fact, [Ca2+]lim was lower with 10 mM p-NPP than
      with 5 mM ATP. The magnitude of passive efflux from Ca-oxalate loaded SR during
      the steady state of [Ca2+]lim was estimated by the unidirectional flux of 45Ca2+,
      and directly, following depletion of ATP, by measuring release of 40Ca2+, and was
      0.02% of Vmax. Constant infusion of CaCl2 at [Ca2+]lim resulted in a new steady
      state, in which active transport into SR vesicles balances the infusion rate.
      Varying infusion rates allows determination of [Ca2+]-dependence of transport in
      the absence of chelating agents. Parameters of non-linear regression were
      Vmax=853 nmol/min per mg, K0.5(Ca)=279 nM, and nH(Ca)=1.89. Since conditions
      employed in this study are similar to those in the sarcoplasm of relaxed muscle,
      it is suggested that histidine, added to media in studies of intracellular Ca2+
      transients, and in the relaxed state, will minimise contribution of Zn2+ to
      fluophore fluorescence, since it occurs at levels predicted in this study to
      cause significant overestimation of cytoplasmic free [Ca2+] in the relaxed state.
      Similar precautions may apply to non-muscle cells as well. This study also
      suggests that [Ca2+]lim in the resting state is a characteristic feature of Ca2+
      pump function, rather than a balance between active transport and passive leakage
      pathways.

PMID- 10209211
TI  - Transbilayer movement and distribution of spin-labelled phospholipids in the
      inner mitochondrial membrane.
AB  - The transmembrane diffusion and equilibrium distribution of spin-labelled
      phosphatidylethanolamine (PE*), phosphatidylcholine (PC*) and cardiolipin (CL*)
      were investigated in purified mitochondrial inner membranes using electron spin
      resonance spectroscopy. Using the back exchange technique, we found that the
      outside-inside movement of PE* and PC* in beef-heart inner mitochondrial
      membranes was rapid (t1/2 in the range 10-15 min at 30 degrees C). The steady
      state distributions in non-energised mitoplasts were approximately 30% in the
      inner leaflet for PC* and 39% for PE*. Within the limits of probe concentration
      that can possibly be used in these experiments, the initial velocity of the
      inward movement was not saturable with respect to the amount of analogue added to
      the membranes, suggesting that the spin-labelled phospholipids diffused passively
      between the two leaflets of the inner mitochondrial membrane. In energised
      mitoplasts, PC* behaviour was not affected, PE* diffused approximately two times
      faster toward the inner monolayer but reached the same plateau. Treatment of
      energised mitochondria with N-ethylmaleimide did not affect PC* diffusion, while
      the kinetics of PE* internalisation became identical to that of PC*. Similar
      results were found when PC* and PE* movements were studied in mitoplasts from
      beef heart, rat liver or yeast. The spin-labelled cardiolipin, which possesses
      four long chains, had to be introduced in the mitoplast with some ethanol. After
      equilibration (t1/2 of the order of 13 min at 30 degrees C), the transmembrane
      distribution suggested that approximately half of the cardiolipin analogue
      remained in the outer leaflet. These results do not allow us to determine if a
      specific protein (or flippase) is involved in the phospholipid transmembrane
      traffic within inner mitochondrial membranes, but they show that lipids can
      rapidly flip through the mitochondrial membrane.

PMID- 10209212
TI  - Interaction of cationic liposomes and their DNA complexes with monocytic leukemia
      cells.
AB  - Cationic liposomes complexed with DNA have been used extensively as non-viral
      vectors for the intracellular delivery of reporter or therapeutic genes in
      culture and in vivo. We examined the relationship between the characteristics of
      the lipoplexes, their mode of interaction with monocytic THP-1 cells and their
      ability to transfect these cells. We determined the size and zeta potential of
      cationic liposomes (composed of 1,2-dioleoyl-3-(trimethylammonium) propane
      (DOTAP) and its mixtures with neutral lipids), and lipoplexes at different (+/-)
      charge ratios. As the (+/-) charge ratio of the lipoplexes decreased to (1/1), a
      significant reduction in zeta potential and an increase in size was observed. The
      increase in size resulted from fusion between liposomes promoted by DNA, as
      demonstrated by a lipid mixing assay, and from aggregation of the complexes.
      Interaction of liposomes and lipoplexes with THP-1 cells was assessed by
      monitoring lipid mixing ('fusion') as well as binding and cell association. While
      no lipid mixing was observed with the 1/2 (+/-) lipid/DNA complexes, lipoplexes
      with higher (+/-) charge ratios underwent significant fusion in conjunction with
      extensive cell binding. Liposome binding to cells was dependent on the positive
      charge of the liposomes, and their fusion could be modulated by the co-lipid.
      DOTAP/phosphatidylethanolamine (1:1) liposomes fused with THP-1 cells, unlike
      DOTAP/phosphatidylcholine (1:1) liposomes, although both liposome types bound to
      the cells to a similar extent. The use of inhibitors of endocytosis indicated
      that fusion of the cationic liposomes with cells occurred mainly at the plasma
      membrane level. The presence of serum increased the size of the cationic
      liposomes, but not that of the lipoplexes. Low concentrations of serum (3%)
      completely inhibited the fusion of cationic liposomes with cells, while
      inhibiting binding by only 20%. Our results suggest that binding of cationic
      liposomes and lipoplexes to cells is governed primarily by electrostatic
      interactions, whereas their fusion is regulated by the lipid composition and
      sterically favorable interactions with cell surface molecules. In addition our
      results indicate no correlation between fusion of the lipoplexes with the plasma
      membrane and the levels of transfection.

PMID- 10209213
TI  - Role of the intracellular domain of the beta subunit in Na,K pump function.
AB  - The catalytic alpha subunit of the (Na,K)- and (H,K)-ATPases needs to be
      coexpressed with a beta subunit in order to produce cation transport activity.
      Although the isoform of the beta subunit is known to influence the functional
      characteristics of the Na,K pump, the role of the different domains of the beta
      subunit is not fully understood. We have studied the function of a Na,K pump
      resulting from the expression of a wild-type alpha subunit with a N-terminally
      truncated mutant of the beta subunit using the two-electrode voltage clamp and
      the cut-open oocyte techniques. While the maximal activity, measured as the K+
      activated outward current, was not significantly altered, the beta N-terminal
      truncation induced an ouabain-sensitive conductance in the absence of
      extracellular K+. The voltage dependence of the ouabain-sensitive charge
      distribution indicated that in the Na/Na exchange conditions, the E1-E2
      conformation equilibrium was shifted towards the E2 conformation, a change
      resulting from alteration of both the forward and the backward reaction rate.
      Removal of the intracellular domain of the beta subunit modifies several aspects
      of the whole enzyme function by a mechanism that must imply the state of the
      extracellular and/or transmembrane parts of the alpha/beta subunit complex.

PMID- 10209214
TI  - Nisin promotes the formation of non-lamellar inverted phases in unsaturated
      phosphatidylethanolamines.
AB  - Nisin, a peptide used as a food preservative, is shown, by 31P-nuclear magnetic
      resonance and infrared spectroscopy, to perturb the structure of membranes formed
      of unsaturated phosphatidylethanolamine (PE) and to induce the formation of
      inverted non-lamellar phases. In the case of dioleoyl-sn-glycero-3
      phosphatidylethanolamine (DOPE), nisin promotes the formation of inverted
      hexagonal phase. Similarly, the peptide induces the formation of an isotropic
      phase, most likely a cubic phase, with 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphatidylethanolamine (POPE). It is proposed that the insertion of the peptide
      in the bilayer shifts the amphiphilic balance by increasing the hydrophobic
      contribution and is at the origin of the changes in the polymorphic propensities
      of PE. This is supported by the fact that the presence of cholesterol in the PE
      bilayer inhibits the power of nisin to perturb the membrane structure, most
      likely because the peptide insertion is difficult in the fluid ordered phase.
      This finding provides insight into possible antibacterial mechanisms of nisin.

PMID- 10209215
TI  - Stabilizing effect of an S-layer on liposomes towards thermal or mechanical
      stress.
AB  - Isolated subunits of the crystalline cell surface layer (S-layer) protein of
      Bacillus stearothermophilus PV72/p2 were recrystallized on positively charged
      unilamellar liposomes. Liposomes were composed of dipalmitoylphosphatidylcholine
      (DPPC), cholesterol and hexadecylamine (HDA) in a molar ratio of 10:5:4 and they
      were prepared by the dehydration-rehydration method followed by an extrusion
      procedure. The S-layer protein to DPPC ratio was 5.7 nmol/micromol which
      approximately corresponds to the theoretical value estimated by using the areas
      occupied by the S-layer lattice and the lipid membrane. Coating of the positively
      charged liposomes with S-layer protein resulted in inversion of the zeta
      potential from +29.1 mV to -27.1 mV. Covalent crosslinking of the recrystallized
      S-layer protein was achieved with glutaraldehyde. Chemical analysis revealed that
      almost all amino groups (>95%) from HDA in the liposomal membrane were involved
      in the reaction. To study the influence of an S-layer lattice on the stability of
      the liposomes, the hydrophilic marker carboxyfluoresceine (CF) was encapsulated
      and its release was determined for plain and S-layer-coated liposomes in the
      course of mechanical and thermal challenges. In comparison to plain liposomes, S
      layer-coated liposomes released only half the amount of enclosed CF upon exposure
      to shear forces or ultrasonication as mechanical stress factors. Furthermore,
      temperature shifts from 25 degrees C to 55 degrees C and vice versa induced
      considerably less CF release from S-layer-coated than from plain liposomes. A
      similar stabilizing effect of the S-layer lattice was observed after
      glutaraldehyde treatment of plain and S-layer-coated liposomes.

PMID- 10209216
TI  - Water transport by the bacterial channel alpha-hemolysin.
AB  - This study is an investigation of the ability of the bacterial channel alpha
      hemolysin to facilitate water permeation across biological membranes. alpha
      Hemolysin channels were incorporated into rabbit erythrocyte ghosts at varying
      concentrations, and water permeation was induced by mixing the ghosts with
      hypertonic sucrose solutions. The resulting volume decrease of the ghosts was
      followed by time-resolved optical absorption at pH 5, 6, and 7. The average
      single-channel permeability coefficient of alpha-hemolysin for water ranged
      between 1.3x10-12 cm/s and 1.5x10-12 cm/s, depending on pH. The slightly
      increased single-channel permeability coefficient at lower pH-values was
      attributed to an increase in the effective pore size. The activation energy of
      water transport through the channel was low (Ea=5.4 kcal/mol), suggesting that
      the properties of water inside the alpha-hemolysin channel resemble those of bulk
      water. This conclusion was supported by calculations based on macroscopic
      hydrodynamic laws of laminar water flow. Using the known three-dimensional
      structure of the channel, the calculations accurately predicted the rate of water
      flow through the channel. The latter finding also indicated that water permeation
      data can provide a good estimate of the pore size for large channels.

PMID- 10209217
TI  - Isolation of a French bean (Phaseolus vulgaris L.) homolog to the beta-glucan
      elicitor-binding protein of soybean (Glycine max L.).
AB  - A high-affinity membrane-bound beta-glucan elicitor-binding protein has been
      purified from microsomal preparations of French bean (Phaseolus vulgaris L.)
      roots. A 5900-fold purification was achieved by affinity chromatography of
      functionally solubilized membrane proteins. The beta-glucan-binding protein had
      an apparent molecular mass of 78 kDa when subjected to SDS-PAGE. Western blot
      analysis showed specific crossreactivity of this French bean protein with an
      antiserum raised against a synthetic peptide representing an internal 15 amino
      acid fragment of the beta-glucan-binding protein from soybean. Northern blot
      analysis with a cDNA probe of the soybean beta-glucan-binding protein gene
      revealed a crosshybridizing transcript of 2.4 kb in French bean. These results
      indicate that the beta-glucan-binding proteins of French bean and soybean are
      conserved homologs involved in beta-glucan elicitor recognition.

PMID- 10209218
TI  - Probing DMPG vesicle surface with a cationic aqueous soluble spin label.
AB  - A small, highly aqueous soluble, deuterated, cationic spin label, 4
      trimethylammonium-2,2,6,6-tetramethylpiperidine-d17-1-oxyl iodide (dCAT1), was
      used to directly monitor the negatively charged DMPG vesicle surface in order to
      test a recent suggestion (Riske et al., Chem. Phys. Lipids, 89 (1997) 31-44) that
      alterations in the surface potential accompanied apparent phase transitions
      observed by light scattering. The temperature dependence of the label partition
      between the lipid surface and the aqueous medium indicated an increase in the
      surface potential at the gel to liquid-crystal transition, supporting the
      previous suggestion. Results at the phase transition occurring at a higher
      temperature were less definitive. Although some change in the dCAT1 ESR spectra
      was observed, the interpretation of the phenomena is still rather unclear. DMPG
      surface potentials were estimated from the dCAT1 partition ratios (surface label
      moles/total label moles), using a simple two-sites model, where the electrostatic
      potential is zero everywhere but at the vesicle surface, and the interaction
      between the spin label and the membrane surface is chiefly electrostatic. The
      Gouy-Chapman-Stern model predicts surface potentials similar to those observed,
      although the measured decrease in the surface potential with ionic strength is
      somewhat steeper than that predicted by the model.

PMID- 10209219
TI  - Potassium ion efflux induced by cationic compounds in yeast.
AB  - Potassium efflux in yeast induced by several cationic compounds showed different
      characteristics. All of the observed efflux required glucose as substrate at the
      concentrations used. For most of them, the phenomenon required binding of the
      cationic compound to the cell surface and increased with the negative cell
      surface charge, and for all the compounds tested, it depended on a metabolizable
      substrate. Efflux induced with terbium chloride appeared more likely due to the
      function of a K+/H+ antiporter. With DEAE-dextran and dihydrostreptomycin,
      potassium efflux was dependent on the cell potassium content and was also
      sensitive to osmotic changes of the medium. DEAE-dextran-provoked efflux was not
      due to cell disruption. Dihydrostreptomycin seemed to activate a potassium efflux
      system which could not be studied in isolation, but its inhibition of potassium
      uptake may also be involved. Except for cells treated with ethidium bromide, no
      appreciable cell disruption was observed. The potassium efflux observed appears
      to be a membrane phenomenon reversible after washing with magnesium chloride.

PMID- 10209220
TI  - Activated stellate (Ito) cells possess voltage-activated calcium current.
AB  - We previously reported stellate (Ito) cells possess voltage-activated Ca2+
      current. The activation of stellate cells has been indicated to contribute to
      liver fibrosis and the regulation of hepatic hemodynamics. The aim of this study
      was to investigate the relationship between voltage-activated Ca2+ current and
      activation of stellate cells. Voltage-activated Ca2+ current in stellate cells
      isolated from rats were studied using whole-cell patch clamp technique. L-type
      voltage-activated Ca2+ current was hardly detected in stellate cells cultured for
      less than 9 days. Ca2+ current was detected 12.5 and 69% of cells at the 10th and
      14th day of culture, respectively. BrdU incorporation indicated cell
      proliferation was recognized over 50% of cells at the 3rd and 5th day of culture,
      respectively, then decreased significantly in a time-dependent manner. On the
      other hand, the expression of alpha-smooth muscle actin indicated cell activation
      increased from 7th day of culture and collagen type I mRNA appeared remarkably in
      cells cultured for more than 10 days. In this study, we concluded L-type voltage
      activated Ca2+ current was recognized in activated stellate (myofibroblast-like)
      cells.

PMID- 10209221
TI  - Cellular uptake of cationic lipid/DNA complexes by cultured myoblasts and
      myotubes.
AB  - Several cationic lipids which are highly efficient for delivering genes in vitro
      do not increase gene delivery in vivo after an intramuscular injection. In order
      to elucidate the origin of this phenomenon, we have studied the cellular uptake
      and intracellular fate of cationic lipid/DNA complexes in vitro on myogenic mouse
      cells (myoblasts and myotubes) of the C2 cell line and of primary cultures. We
      used a cationic lipid with a spermine head group and its fluorescent analog, and
      a fluorescent plasmid obtained by nick-translation. In myoblasts, transgene
      expression was obtained and lipoplexes were internalized in cytoplasmic vesicles.
      In myotubes, no transgene expression could be detected and we observed an absence
      of lipoplex internalization. The in vitro uptake of cationic lipid was inversely
      correlated with the degree of fusion of C2 cell myotubes cultures.

PMID- 10209222
TI  - Determinants of potassium channel assembly localised within the cytoplasmic C
      terminal domain of Kv2.1.
AB  - The C-terminal domain of the voltage-gated potassium channel Kv2.1 is shown to
      have a role in channel assembly using dominant negative experiments in Xenopus
      oocytes. Kv2.1 channel polypeptides were co-expressed with a number of
      polypeptide fragments of the cytosolic C-terminus and the assembly of functional
      channel homotetramers quantified electrophysiologically using the two electrode
      voltage clamp technique. Co-expression of C-terminal polypeptides corresponding
      to the final 440, 318, 220 and 150 amino acid residues of Kv2.1 all resulted in a
      significant reduction in the functional expression of the full-length channel. A
      truncated version of Kv2.1 lacking the final 318 amino acids of the C-terminal
      domain (Kv2. 11-535) exhibited similar electrophysiological properties to the
      full-length channel. Co-expression with either the 440 or 318 residue
      polypeptides resulted in a reduction in the activity of the truncated channel. In
      contrast, the 220 and 150 residue C-terminal fragments had no effect on Kv2.11
      535 activity. These data demonstrate that C-terminal interactions are important
      for driving Kv2.1 channel assembly and that distinct regions of the C-terminal
      domain may have differential effects on the formation of functional tetramers.

PMID- 10209223
TI  - Docosahexaenoic acid (DHA) alters the phospholipid molecular species composition
      of membranous vesicles exfoliated from the surface of a murine leukemia cell
      line.
AB  - Previously, we presented evidence that the vesicles routinely exfoliated from the
      surface of T27A tumor cells arise from vesicle-forming regions of the plasma
      membrane and possess a set of lateral microdomains distinct from those of the
      plasma membrane as a whole. We also showed that docosahexaenoic acid (DHA, or
      22:6n-3), a fatty acyl chain known to alter microdomain structure in model
      membranes, also alters the structure and composition of exfoliated vesicles,
      implying a DHA-induced change in microdomain structure on the cell surface. In
      this report we show that enrichment of the cells with DHA reverses some of the
      characteristic differences in composition between the parent plasma membrane and
      shed microdomain vesicles, but does not alter their phospholipid class
      composition. In untreated cells, DHA-containing species were found to be a much
      greater proportion of the total phosphatidylethanolamine (PE) pool than the total
      phosphatidylcholine (PC) pool in both the plasma membrane and the shed vesicles.
      After DHA treatment, the proportion of DHA-containing species in the PE and PC
      pools of the plasma membrane were elevated, and unlike in untreated cells, their
      proportions were equal in the two pools. In the vesicles shed from DHA-loaded
      cells, the proportion of DHA-containing species of PE was the same as in the
      plasma membrane. However, the proportion of DHA-containing species of PC in the
      vesicles (0.089) was much lower than that found in the plasma membrane (0.194),
      and was relatively devoid of species with 16-carbon acyl components. These data
      suggested that DHA-containing species of PC, particularly those having a 16
      carbon chain in the sn-1 position, were preferentially retained in the plasma
      membrane. The data can be interpreted as indicating that DHA induces a
      restructuring of lateral microdomains on the surface of living cells similar to
      that predicted by its behavior in model membranes.

PMID- 10209225
TI  - The influence of vitamin K1 on the structure and phase behaviour of model
      membrane systems.
AB  - Vitamin K1 is a component of the Photosystem I of plants which constitutes the
      major dietary form of vitamin K. The major function of this vitamin is to be
      cofactor of the microsomal gamma-glutamylcarboxylase. Recently, novel roles for
      this vitamin in the membrane have been postulated. To get insight into the
      influence of vitamin K1 on the phospholipid component of the membrane, we have
      studied the interaction between vitamin K1 and model membranes composed of
      dimyristoylphosphatidylcholine (DMPC) and dielaidoylphosphatidylethanolamine
      (DEPE). We utilized high-sensitivity differential scanning calorimetry and small
      angle X-ray diffraction techniques. Vitamin K1 affected the thermotropic
      properties of the phospholipids, broadened and shifted the transitions to lower
      temperatures, and produced the appearance of several peaks in the thermograms.
      The presence of the vitamin gave rise to the formation of vitamin-rich domains
      which were immiscible with the bulk phospholipid in both the gel and the liquid
      crystalline phases. Vitamin K1 was unable to alter the lamellar organization of
      DMPC, but we found that it produced an increase in the interlamellar repeat
      spacing of DMPC at 10 degrees C. Interestingly, vitamin K1 promoted the formation
      of inverted hexagonal HII structures in the DEPE system. We discuss the possible
      implications that these vitamin K1-phospholipid interactions might have with
      respect to the biological function of the vitamin.

PMID- 10209224
TI  - Self-aggregation of triadin in the sarcoplasmic reticulum of rabbit skeletal
      muscle.
AB  - The 95 kDa transmembrane glycoprotein triadin is believed to be an essential
      component of excitation-contraction coupling in the junctional sarcoplasmic
      reticulum of skeletal muscle fibers. It is debatable whether triadin mediates
      intraluminal interactions between calsequestrin and the ryanodine receptor
      exclusively or whether this junctional protein provides also a cytoplasmic
      linkage between the Ca2+-release channel and the dihydropyridine receptor. Here,
      we could show that native triadin exists as disulfide-linked homo-polymers of
      above 3000 kDa. Under non-reducing conditions, protein bands representing the
      alpha1-dihydropyridine receptor and calsequestrin did not show an
      immunodecorative overlap with the extremely high-molecular-mass triadin clusters.
      Following chemical crosslinking, the ryanodine receptor and triadin exhibited a
      similarly decreased electrophoretic mobility. However, immunoblotting of diagonal
      non-reducing/reducing two-dimensional gels clearly demonstrated a lack of overlap
      between the immunodecorated bands representing triadin, the alpha1
      dihydropyridine receptor, the ryanodine receptor and calsequestrin. Thus, in
      native membranes triadin appears to form large self-aggregates primarily.
      Although triadin exists in a close neighborhood relationship to the Ca2+-release
      channel tetramers, it does not seem to be directly linked to the other main triad
      components implicated in the regulation of the excitation-contraction-relaxation
      cycle and Ca2+-homeostasis. This agrees with a proposed role of triadin in the
      maintenance of overall triad architecture.

PMID- 10209226
TI  - Benzodiazepine localisation at the lipid-water interface: effect of membrane
      composition and drug chemical structure.
AB  - The effect of membrane chemical composition and drug chemical structure on the
      localisation of several benzodiazepines (BZDs) (DZ, diazepam; CZ, clonazepam; CX,
      chlordiazepoxide) within model membranes was investigated. We used a
      spectrophotometric method presented in a previous paper (B.A. Garcia, M.A.
      Perillo, Biochim. Biophys. Acta 1324 (1997) 76-84) based on the study of BZD acid
      base equilibrium. 'Intrinsic pK' values (pKi) were calculated according to the
      theory of M.S. Fernandez and P. Fromherz (J. Phys. Chem. 81 (1977) 1755-1761).
      Homogeneous media of known dielectric constant (dioxane 0-80% v/v in water) were
      used to construct a curve of DeltapKi (pKi-pKw) vs. dielectric constant (D) where
      DeltapKi values obtained in lipidic dispersions were interpolated. In
      heterogeneous media consisting of aqueous dispersions of Triton X-100 micelles we
      determined the relative localisation depth of BZDs according to their DTriton
      values (36, 37 and 62 for DZ, CX and CZ respectively) taking into account that
      lower D values correspond to deeper localisation. pKi determined in dispersions
      of dipalmitoylphosphatidylcholine (dpPC) and egg phosphatidylcholine (egg-PC)
      mixed multilamellar vesicles showed that, when cholesterol content increased from
      0 to 20 mole%, D values decreased (from 59 to 40) in dpPC vesicles and increased
      (from 51 to 72) in egg-PC vesicles, indicating a tendency of BZDs to penetrate
      deeper into less ordered interfaces. These results should be considered to
      understand the non-specific pharmacological effects of BZDs as well as to
      evaluate the actual relevance of their pharmacological concentrations.

PMID- 10209227
TI  - A novel strategy affords high-yield coupling of antibody to extremities of
      liposomal surface-grafted PEG chains.
AB  - Several methodologies for the preparation of polyethylene glycol-grafted
      immunoliposomes have been developed by attaching antibodies to the terminus of
      the polymer. Unilamellar liposomes were prepared containing a combination of a
      functionalized polyethylene glycol(3400) and an inert polyethylene glycol(2000)
      phosphatidylethanolamine derivate up to 5 mol%. The greater length of the
      functionalized polyethylene glycol derivate did not alter the liposomal sterical
      stability or the remote loading of doxorubicin. Anti-CD34 immunoliposomes were
      prepared by the reaction of maleimide-derivatized My10 antibody with generated
      thiol groups at the periphery of the liposomes and efficiencies of nearly 100%
      were obtained. The greater accessibility of the reactive group makes this
      strategy more efficient than others described. The immunoliposomes prepared bound
      specifically to CD34+ cells.

PMID- 10209228
TI  - Identity of the F52F12.1 gene product in Caenorhabditis elegans as an organic
      cation transporter.
AB  - We describe here the cloning and functional characterization of an organic cation
      transporter from Caenorhabditis elegans (CeOCT1). The CeOCT1 cDNA is 1826 bp long
      and codes for a protein of 568 amino acids. The oct1 gene is approximately 3.2 kb
      in size and consists of 12 exons. The location of this gene corresponds to the
      F52F12.1 gene locus on chromosome I. The predicted protein contains 12 putative
      transmembrane domains. It exhibits significant homology to mammalian OCTs. When
      expressed in mammalian cells, CeOCT1 induces the transport of the prototypical
      organic cation tetraethylammonium. The Michaelis-Menten constant for this
      substrate is 80+/-16 microM. The substrate specificity of CeOCT1 is broad. This
      represents the first report on the cloning and functional characteristics of an
      organic cation transporter from C. elegans.

PMID- 10209229
TI  - Molecular cloning and sequencing of the cDNA for vacuolar H+-pyrophosphatase from
      Chara corallina1.
AB  - We have cloned a cDNA for vacuolar proton-translocating pyrophosphatase of Chara
      corallina that is one of the closest green algae to the land plants. The deduced
      protein consists of 793 amino acid residues. Its sequence is 71% identical to the
      H+-pyrophosphatases of land plants, and is less than 46% identical to those of
      marine alga and phototrophic bacterium.

PMID- 10209230
TI  - Neuronal death and survival in two models of hypoxic-ischemic brain damage.
AB  - Two unilateral hypoxic-ischemia (HI) models (moderate and severe) in immature rat
      brain have been used to investigate the role of various transcription factors and
      related proteins in delayed neuronal death and survival. The moderate HI model
      results in an apoptotic-like neuronal death in selectively vulnerable regions of
      the brain while the more severe HI injury consistently produces widespread
      necrosis resulting in infarction, with some necrosis resistant cell populations
      showing evidence of an apoptotic type death. In susceptible regions undergoing an
      apoptotic-like death there was not only a prolonged induction of the immediate
      early genes, c-jun, c-fos and nur77, but also of possible target genes amyloid
      precursor protein (APP751) and CPP32. In contrast, increased levels of BDNF,
      phosphorylated CREB and PGHS-2 were found in cells resistant to the moderate HI
      insult suggesting that these proteins either alone or in combination may be of
      importance in the process of neuroprotection. An additional feature of both the
      moderate and severe brain insults was the rapid activation and/or proliferation
      of glial cells (microglia and astrocytes) in and around the site of damage. The
      glial response following HI was associated with an upregulation of both the CCAAT
      enhancer binding protein alpha (microglia only) and NFkappaB transcription
      factors.

PMID- 10209231
TI  - EEG alpha and theta oscillations reflect cognitive and memory performance: a
      review and analysis.
AB  - Evidence is presented that EEG oscillations in the alpha and theta band reflect
      cognitive and memory performance in particular. Good performance is related to
      two types of EEG phenomena (i) a tonic increase in alpha but a decrease in theta
      power, and (ii) a large phasic (event-related) decrease in alpha but increase in
      theta, depending on the type of memory demands. Because alpha frequency shows
      large interindividual differences which are related to age and memory
      performance, this double dissociation between alpha vs. theta and tonic vs.
      phasic changes can be observed only if fixed frequency bands are abandoned. It is
      suggested to adjust the frequency windows of alpha and theta for each subject by
      using individual alpha frequency as an anchor point. Based on this procedure, a
      consistent interpretation of a variety of findings is made possible. As an
      example, in a similar way as brain volume does, upper alpha power increases (but
      theta power decreases) from early childhood to adulthood, whereas the opposite
      holds true for the late part of the lifespan. Alpha power is lowered and theta
      power enhanced in subjects with a variety of different neurological disorders.
      Furthermore, after sustained wakefulness and during the transition from waking to
      sleeping when the ability to respond to external stimuli ceases, upper alpha
      power decreases, whereas theta increases. Event-related changes indicate that the
      extent of upper alpha desynchronization is positively correlated with (semantic)
      long-term memory performance, whereas theta synchronization is positively
      correlated with the ability to encode new information. The reviewed findings are
      interpreted on the basis of brain oscillations. It is suggested that the encoding
      of new information is reflected by theta oscillations in hippocampo-cortical
      feedback loops, whereas search and retrieval processes in (semantic) long-term
      memory are reflected by upper alpha oscillations in thalamo-cortical feedback
      loops.

PMID- 10209232
TI  - An update on GABAA receptors.
AB  - Recent advances in molecular biology and complementary information derived from
      neuropharmacology, biochemistry and behavior have dramatically increased our
      understanding of various aspects of GABAA receptors. These studies have revealed
      that the GABAA receptor is derived from various subunits such as alpha1-alpha6,
      beta1-beta3, gamma1-gamma3, delta, epsilon, pi, and rho1-3. Furthermore, two
      additional subunits (beta4, gamma4) of GABAA receptors in chick brain, and five
      isoforms of the rho-subunit in the retina of white perch (Roccus americana) have
      been identified. Various techniques such as mutation, gene knockout and
      inhibition of GABAA receptor subunits by antisense oligodeoxynucleotides have
      been used to establish the physiological/pharmacological significance of the
      GABAA receptor subunits and their native receptor assemblies in vivo. Radioligand
      binding to the immunoprecipitated receptors, co-localization studies using
      immunoaffinity chromatography and immunocytochemistry techniques have been
      utilized to establish the composition and pharmacology of native GABAA receptor
      assemblies. Partial agonists of GABAA receptors are being developed as
      anxiolytics which have fewer and less severe side effects as compared to
      conventional benzodiazepines because of their lower efficacy and better
      selectivity for the GABAA receptor subtypes. The subunit requirement of various
      drugs such as anxiolytics, anticonvulsants, general anesthetics, barbiturates,
      ethanol and neurosteroids, which are known to elicit at least some of their
      pharmacological effects via the GABAA receptors, have been investigated during
      the last few years so as to understand their exact mechanism of action.
      Furthermore, the molecular determinants of clinically important drug-targets have
      been investigated. These aspects of GABAA receptors have been discussed in detail
      in this review article.

PMID- 10209233
TI  - Basement membranes, microfibrils and beta amyloid fibrillogenesis in Alzheimer's
      disease: high resolution ultrastructural findings.
AB  - It is known that beta amyloid fibrils are deposited at the basement membrane of
      the cerebromicrovasculature in the brains of patients with Alzheimer's disease,
      and the assembly of the fibrils may be in continuation with the core of senile
      plaques. The fibrils accumulate in a manner similar to that in which microfibrils
      accumulate in the glomerular basement membrane of the rat kidney during long-term
      experimental diabetes, and in the alveolar-capillary basement membrane of the
      normal lung. beta amyloid fibrils in-situ are known to be about 10 nm wide
      tubular structures and they closely resemble connective tissue microfibrils. Our
      recent high resolution ultrastructural studies combined with immunogold labeling
      demonstrated that beta amyloid fibrils in-situ are indeed microfibril-like
      structures, and the beta protein is associated with their surface in the form of
      loose assemblies of 1 nm wide flexible filaments. Thus, the result of this study
      indicates that in-situ a major component of the beta amyloid deposit is the
      microfibril-like structure. The elucidation of the mechanism of cerebral beta
      amyloid fibrillogenesis in Alzheimer's disease may therefore require
      understanding the mechanism of 'normal' microfibrils biogenesis.

PMID- 10209234
TI  - The p21-Ras signal transduction pathway and growth regulation in human high-grade
      gliomas.
AB  - Deregulated p21-Ras function, as a result of mutation, overexpression or growth
      factor-induced overactivation, contributes to at least 30% of human cancer. This
      article reviews the potential role of the p21-Ras family of GTPases in the
      regulation of growth of high-grade gliomas and describes how targeting this
      oncoprotein clinically may provide a novel strategy to counteract glioma
      proliferation. The application of strategies directed at selectively opposing the
      deregulated signal transduction pathway of high-grade gliomas may be of potential
      therapeutic benefit and may offer a whole new arsenal of antineoplastic agents to
      be included in the multimodal treatment of these challenging neoplasms.

PMID- 10209235
TI  - An integrated view of pathophysiological models of schizophrenia.
AB  - Pathophysiological processes that underlie the profound neuropsychiatric
      disturbances in schizophrenia are poorly understood. However, the clinical course
      of the disease, and a number of clinical and basic science observations, provide
      direction for formulating pathophysiological models that could be empirically
      tested. For example, repeated psychostimulant administration to healthy subjects
      can induce psychotic symptoms, and acute stimulant challenge in schizophrenia
      patients can precipitate psychosis. Also, NMDA antagonists induce positive,
      negative, and cognitive schizophrenic-like symptoms in healthy volunteers and
      precipitate thought disorder and delusions in schizophrenia patients. These human
      studies provide support for the dopamine and NMDA receptor hypofunction
      hypotheses of schizophrenia. Well-documented effects of NMDA antagonists on
      dopamine systems provide a basis to integrate the dopamine and NMDA receptor
      hypofunction hypotheses. Furthermore, it has become apparent that prominent
      actions of antipsychotic drugs, especially those with 'atypical' properties,
      involve antagonism of behavioral, electrophysiological and brain metabolic
      effects produced by administration of NMDA receptor antagonists. A confluence of
      clinical and basic science data suggests that an early developmental insult,
      potentially involving reduced NMDA receptor function, could facilitate
      sensitization of dopamine systems, leading to the formal onset of schizophrenia
      in late adolescence and early adulthood. Although clearly speculative, this
      conceptual model is consistent with existing evidence and suggests lines of
      future experimental investigation.

PMID- 10209236
TI  - Corpora-amylacea and the family of polyglucosan diseases.
AB  - The history, characters, composition and topography of corpora amylacea (CA) in
      man and the analogous polyglucosan bodies (PGB) in other species are documented,
      noting particularly the wide variation in the numbers found with age and in
      neurological disease. Their origins from both neurons and glia and their probable
      migrations and ultimate fate are discussed. Their presence is also noted in other
      organs, particularly in the heart. The occurrence in isolated cases of occasional
      'massive' usually focal accumulations of similar polyglucosan bodies in
      association with certain chronic neurological diseases is noted and the specific
      conditions Adult Polyglucosan body disease and type IV glycogenosis where they
      are found throughout the nervous system in great excess is discussed. The
      distinctive differences of CA from the PGB of Lafora body disease and
      Bielschowsky body disease are emphasised. When considering their functional
      roles, a parallel is briefly drawn on the one hand between normal CA and the
      bodies in the polyglucosan disorders and on the other with the lysosomal system
      and its associated storage diseases. It is suggested that these two systems are
      complementary ways by which large, metabolically active cells such as neurons,
      astrocytes, cardiac myocytes and probably many other cell types, dispose of the
      products of stressful metabolic events throughout life and the continuing
      underlying process of aging and degradation of long lived cellular proteins. Each
      debris disposal system must be regulated in its own way and must inevitably, a
      priori, be heir to metabolic defects that give rise in each to its own set of
      metabolic disorders.

PMID- 10209238
TI  - The distribution of FOS-immunoreactive neurons in the brainstem, midbrain and
      diencephalon of fetal sheep in response to acute hypoxia in mid and late
      gestation.
AB  - FOS immunohistochemistry was used to map the distribution of neuronal pathways
      activated by hypoxia in fetal sheep. Conscious pregnant sheep were exposed to
      hypoxia (7-9% O2, 1-2% CO2, balance N2) for 2 h at either 100-105 days (n=5) or
      130-133 days gestation (n=5); term is approximately 147 days. The hypoxia caused
      cessation of breathing movements at both fetal ages, and increased FOS staining
      in the medulla (area postrema, dorsal motor nucleus of vagus, nucleus solitary
      tract, ventrolateral medulla); pons (locus coeruleus and subcoeruleus, lateral
      and medial parabrachial nuclei); midbrain (habenula, periaqueductal grey,
      substantia nigra, areas ventrolateral to Red Nucleus); and hypothalamus (anterior
      and lateral hypothalamic areas, paraventricular and supraoptic nuclei). The
      results were essentially the same at both gestational ages, except that hypoxia
      increased FOS-staining in the habenula only in the older fetuses. The presence of
      FOS protein in pontomedullary cardiorespiratory nuclei at 100-105 days gestation
      indicates that the peripheral chemoreceptors respond to hypoxia at this early
      age, and in the subcoeruleus and medial parabrachial regions of the pons is
      consistent with lesion studies suggesting these areas mediate the inhibition of
      fetal breathing in response to hypoxia. FOS staining in the ventrolateral
      periaqueductal grey and habenula was unexpected, and suggests that pathways
      normally involved in response to noxious stimuli, or which are part of the
      hypothalamic 'defense' response are activated by hypoxia in the fetus. Some FOS
      labelling could arise secondarily as a consequence of the cardiovascular and
      endocrine responses to hypoxia.

PMID- 10209237
TI  - Postnatal development of muscarinic autoreceptors in the rat brain: lateral and
      medial septal nuclei and the diagonal band of Broca.
AB  - The postnatal development of the release of acetylcholine (ACh) and of
      presynaptic, release-inhibiting muscarinic autoreceptors was studied in the
      lateral septum (LS), the medial septum (MS) and the diagonal band of Broca (DB)
      of the rat brain. To this end, slices (350 micrometer thick) containing these
      brain regions from rats of various postnatal ages (postnatal day 3 [P3] to P16,
      and adult) were pre-incubated with [3H]choline and stimulated twice (S1, S2: 360
      pulses, 3 Hz) during superfusion with physiological buffer containing
      hemicholinium-3 (10 microM). In addition, the activity of choline
      acetyltransferase (ChAT, in crude homogenates) was determined as a marker for the
      development of cholinergic functions. At any postnatal age, the electrically
      evoked overflow of tritium from slices pre-incubated with [3H]choline was highest
      in the DB, followed by the MS whereas in slices containing the LS, it was only
      small. In all septal regions, the evoked [3H]overflow was Ca2+-dependent and
      tetrodotoxin-sensitive at P3. It increased with postnatal age and reached about
      60% of the corresponding adult levels at P16. Presence of the muscarinic agonist
      oxotremorine (1 microM) during S2 significantly inhibited the evoked overflow of
      tritium beginning from P5: no significant effect was detected at P3. The ACh
      esterase inhibitor physostigmine (1 microM) exhibited significant inhibitory
      effects from P13 onwards, whereas the muscarinic antagonist atropine (1 microM)
      did not change the evoked ACh release. The activity of ChAT, as measured for
      these septal regions at various postnatal ages, correlated well with the
      [3H]overflow induced by electrical stimulation. In conclusion, (1) electrically
      evoked release of ACh was measured for the first time in three septal subregions;
      (2) the postnatal development of the presynaptic cholinergic functions: ChAT
      activity, ACh release and muscarinic autoreceptors occurs almost synchronously in
      these regions of the septal complex and parallels that in the hippocampal
      formation; (3) as in the hippocampus, the postnatal development of autoreceptors
      was delayed with respect to the exocytotic release of ACh.

PMID- 10209239
TI  - Growth factors effects on the expression of morphological and biochemical
      properties of avian embryonic sympathetic cells. Emphasis on NGF.
AB  - Growth factors are known to be important agents in the differentiation and
      modulation of neuronal phenotypes. We have analyzed the effect of several growth
      factors on the modulation of morphological and biochemical properties of avian
      embryonic sympathetic neurons. The growth factors studied include: nerve growth
      factor (NGF), neurotrophin-3 (NT-3), brain derived neurotrophic factor (BDNF),
      ciliary neurotrophic factor (CNTF), basic fibroblast growth factor (bFGF) and
      transforming growth factor beta-1 (TGF-beta1). Morphological properties were
      analyzed by immunocytochemistry to neurofilament proteins and visualization of
      fibers after glyoxylic acid-induced fluorescence. Biochemical modulation was
      determined by radioimmunoanalysis for the peptides enkephalin (ENK), somatostatin
      (SS) and neuropeptide Y (NPY) and by HPLC-electrochemistry quantification of
      catecholamines. Similar to previous results using chromaffin cell cultures [R.
      Ramirez-Ordonez, J.E. Garcia-Arraras, Peptidergic, catecholaminergic and
      morphological properties of avian chromaffin cells are modulated distinctively by
      growth factors, Dev. Brain Res., 87 (1995) 160-171], we found a dissociation in
      the modulation of biochemical and morphological properties, however, the effect
      of specific factors differed between the chromaffin and sympathetic cultures. We
      have focused on NGF to analyze its effect on the sympathetic peptide phenotypes
      and its lack of an effect on the chromaffin cell peptide phenotypes. The results
      presented here, establish interesting differences between chromaffin cells and
      sympathetic neurons that are of importance to studies of cell lineage and
      differentiation.

PMID- 10209240
TI  - Role of nitric oxide in a fast retrograde signal during development.
AB  - Two retrograde signals influence the chick embryo's isthmo-optic nucleus, which
      projects to the retina: a slow-acting survival signal due to uptake of
      neurotrophic factors, and a fast-acting death signal initiated by calcium entry
      into isthmo-optic terminals due to electrical activity. The latter signal also
      affects dendritic reorganization. Since nitric oxide synthase is present in
      isthmo-optic terminals and their retinal target cells, we have tested its
      possible role in the fast-acting signal. Intraocular injection of nitric oxide
      antagonists led within 6-12 h to a reduction in the number of dying isthmo-optic
      neurons and slowed dendritic reorganization. Surprisingly, nitric oxide agonists
      had a similar fast effect on neuronal death. Although the mechanism appears to be
      complex, nitric oxide is involved in mediating the fast-acting retrograde signal.

PMID- 10209241
TI  - Developmental analysis of the peripheral olfactory organ of the opossum
      Monodelphis domestica.
AB  - The gray, short-tailed opossum, Monodelphis domestica, is born in a very immature
      state after a brief (14-day) gestation. As a result, the species provides a
      unique opportunity to examine very early periods of mammalian development. The
      present study provides the first detailed morphometric analysis of the
      development of the olfactory mucosa and the nasal cavity in Monodelphis. The
      extent of the sensory mucosa increases dramatically across development, covering
      a growing nasal cavity and increasingly elaborate turbinates. Both nasal cavity
      convolution (a measure of turbinate complexity) and mucosal surface area show
      extensive growth between birth and adulthood. These measurements are greatest in
      the central portion of the mucosa (in the caudal portion of the nose) at all ages
      examined. A developmental BrdU study reveals a robust decrease in cellular
      proliferation with age; proliferation decreases to near adult-like patterns by
      postnatal day (P) 40. Results from these studies show that there is dramatic
      structural and cellular postnatal growth in the opossum peripheral olfactory
      organ.

PMID- 10209242
TI  - Neural and behavioral effects of intracranial 192 IgG-saporin in neonatal rats:
      sexually dimorphic effects?
AB  - The consequences of neonatal cholinergic lesions were examined in male and female
      rats. Rats were injected intraventricularly with 600 ng of 192 IgG-saporin at 7
      days of age and examined behaviorally and histologically at 21, 45 and 90 days of
      age. 192 IgG-saporin profoundly reduced low affinity neurotrophin receptor
      (p75NTR)-immunoreactive (IR) and, to a lesser extent, choline acetyltransferase
      IR cells in the basal forebrain. Presumptive sympathetic ingrowths (p75NTR- and
      dopamine beta-hydroxylase-IR) into the hippocampus were first apparent at 45 days
      of age and were not significantly greater at 90 days. Behaviorally, 192 IgG
      saporin increased the time females, but not males, spent on the open arms of the
      elevated plus maze. Lesioned rats had longer platform location latencies in the
      Morris water maze only at the first hidden platform training session and did not
      differ on the rate of learning the platform location or on the no-platform probe
      trial. Generally, the effects of neonatal cholinergic lesions were not sex
      dependent and are unlikely to model Rett syndrome, a disorder characterized by
      forebrain cholinergic deficit which is seen almost exclusively in females.

PMID- 10209243
TI  - Inhibiting neuronal migration by blocking NMDA receptors in the embryonic rat
      cerebral cortex: a tissue culture study.
AB  - To investigate the role of the NMDA receptor on neuronal migration in the
      cerebral cortex, we performed a tissue culture study using embryonic rat brain.
      After we labeled progenitor cells in the ventricular zone of E16 cerebral cortex
      explants by [3H]thymidine, the explants were cultured for 48 h. Then distribution
      of labeled cells was evaluated autoradiographically. Blocking NMDA receptors by
      adding the NMDA receptor antagonist, (+)-5-methyl-10, 11-dihydro-5H
      dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801: 1 or 10 microM) or
      d(-)-2-amino-5-phosphonopentanoic acid (d-AP5: 100 microM) to the culture medium,
      caused significantly decreased distribution of labeled cells in the outer
      intermediate zone (control 14.2+/-5.5%, 1 microM MK-801 5.8+/-7.2%, 10 microM MK
      801 3.6+/-1.4%, and d-AP5 8.6+/-4.0%; mean+/-S.D.). This suggests that blocking
      NMDA receptors inhibits neuronal migration in the cerebral cortex. Furthermore,
      the influence of decreased intracellular Ca2+ concentration on neuronal migration
      was examined by adding intracellular Ca2+ chelator, 1, 2-bis-(o-aminophenoxy)
      ethane-N,N,N',N'-tetraacetic acid tetra-(acetoxymethyl)-ester (BAPTA-AM: 5 or 25
      microM). This also resulted in inhibited neuronal migration. Therefore, it seems
      that neuronal migration in the cerebral cortex is regulated by intracellular Ca2+
      concentration, which the NMDA receptor may influence.

PMID- 10209244
TI  - Growth inhibitory effects of a mu opioid on cultured cholinergic neurons from
      fetal rat ventral forebrain, brainstem, and spinal cord.
AB  - Cholinergic pathways play a role in respiration in the mammalian brain, and
      agents that affect respiratory function such as opioid peptides might have
      positive or negative neurotrophic effects during the development of these
      cholinergic connections. Rat fetal nerve cell cultures from developmental stages
      E14-E18 were established in 96-well plates from ventral forebrain (VFB), an area
      rich in cholinergic neurons, and from brainstem and rostral spinal cord, areas
      where respiratory control systems and cholinergic neurons co-exist. High affinity
      3H-choline uptake was highest in E14 VFB cultures and decreased to 20% of this
      value by E16 and E18. Choline uptakes in E14 brainstem and spinal cord were only
      20% and 13%, respectively, of E14 VFB uptake. A mu opioid receptor agonist, d
      ala2-mePhe4-gly(ol)5]-enkephalin (DAMGO), was tested for its effect on somal area
      and neurite outgrowth in E16 cultures. Cholinergic neurons were identified by
      immunostaining with choline acetyltransferase antibody. DAMGO (10(-8) M)
      significantly decreased somal area in VFB cultures and spinal cord, but had no
      effect on somal area in brainstem. Naltrexone (10(-6) M) reversed this
      inhibition. Spinal cord cell neurite outgrowth was inhibited by DAMGO, and this
      inhibition was reversed by naltrexone. DAMGO had no significant effect on neurite
      length in VFB. Brainstem neurite length was paradoxically increased by both DAMGO
      and naltrexone. It was concluded that mu-selective opioid peptides inhibit growth
      of cultured cholinergic neurons in VFB and spinal cord, but not in the brainstem.
      There was no evidence for endogenous opioid activity in either VFB or spinal cord
      cultures.

PMID- 10209245
TI  - Developmental study of miniature IPSCs of CA3 hippocampal cells: modulation by
      midazolam.
AB  - Maturation of GABAA/benzodiazepine receptors is associated with changes in their
      subunit composition. We have investigated whether these changes are accompanied
      by a developmental modification in the kinetic properties of miniature IPSCs
      (mIPSCs) and sensitivity to midazolam, a benzodiazepine agonist. In the presence
      of TTX (10 microM) and excitatory amino acid antagonists, AP5 (50 microM) and
      CNQX (50 microM), we whole-cell recorded mIPSCs in CA3 cells of hippocampal
      slices of adult and young (4-8 days) rats. mIPSCs were mediated by GABAA
      receptors as they were suppressed by bicuculline (10 microM). In both the adult
      and young rats, mIPSCs were similar in amplitude and kinetic properties. However,
      the mIPSCs frequency markedly increased with age from 4+/-3 Hz in the young rats
      to 20+/-9 Hz in the adult rats. In both age groups, midazolam (0.01 microM(-10)
      microM) and pentobarbital (30 microM) did not affect the amplitude, frequency and
      rise time of the mIPSCs but they increased to a similar extent their decay time
      constant. The current responses to isoguvacine, a GABAA agonist, were potentiated
      by 0.1 microM midazolam in both age groups. It is concluded that in immature and
      adult rats, synaptic GABAA receptors of CA3 were not different in their kinetic
      properties and sensitivity to midazolam.

PMID- 10209246
TI  - Muscarinic receptor- and phorbol ester-stimulated phosphorylation of protein
      kinase C substrates in adult and neonatal cortical slices.
AB  - The neuron-specific protein B-50 (GAP-43) is a major presynaptic substrate for
      protein kinase C (PKC). Phosphorylation of B-50 by PKC at serine-41 is
      functionally related to signal transduction in association with process outgrowth
      and neurotransmitter release. Thus, it is important to characterize the factors
      which modulate phosphorylation of B-50 by PKC. Phosphoinositide (PI)-coupled
      muscarinic acetylcholine receptor (mAchR) activation would be expected to
      increase PKC activity through production of the second messenger, diacylglycerol.
      To test the hypothesis that activation of mAchR also increases phosphorylation of
      B-50, protein phosphorylation has been examined in cerebral cortical slices in
      response to the cholinergic agonist, carbachol (Cch) in comparison to the phorbol
      ester, 4beta-phorbol 12, 13-dibutyrate (PDB), a known activator of PKC. At short
      times of incubation with 1 mM Cch, a concentration which maximally activates PI
      metabolism, increased phosphorylation of a group of synaptosomal proteins,
      including B-50 and myristoylated, alanine-rich C kinase substrate (MARCKS), was
      observed. This increase was approximately half of that obtained in response to 1
      microM PDB. Differing patterns of protein phosphorylation were observed in
      neonatal and adult slices: neonatal samples contained more MARCKS and a PKC
      substrate with a Mr of 46 kDa. Phosphorylation of B-50 and MARCKS was sensitive
      to Cch in both cases. Immunoblotting demonstrated less m1 acetylcholine receptor
      (the predominant mAchR subtype coupled to PI metabolism in the cortex) in
      neonatal, as compared to adult, synaptosomal fractions. These results are
      consistent with a coupling between mAchR-stimulated PI metabolism and PKC
      mediated protein phosphorylation that is developmentally regulated.

PMID- 10209247
TI  - Different patterns of abnormal neuronal migration in the cerebral cortex of mice
      prenatally exposed to irradiation.
AB  - A characteristic abnormal cortical architecture in the adult brain was produced
      in mice subjected to 1.5 Gy of X-irradiation on embryonic day 14. Neurons in the
      lateral regions were organized into an essentially six-layered structure, while
      neurons in the dorsal regions formed a unique four-layered cortex. The patterns
      of neuronal migration in these different cortical regions were examined with
      immunohistochemistry for anti-bromodeoxyuridine (BrdU), anti-midkine (MK), and
      anti-glial fibrillary acidic protein (GFAP) antibodies. In the cortical lateral
      region, BrdU-labeled cells in the upper layers were fewer, and those in lower
      layers more numerous in prenatally irradiated mice than in control, while in the
      dorsal region (four-layered region), BrdU-labeled cells were very few in layer 2,
      and a large number of labeled-cells remained in layer 4. These results indicated
      that some neuroblasts in the lateral cortical region could not migrate to the
      upper layers, and that most neuroblasts in the dorsal cortical region failed to
      pass through the earlier migration zone. MK- and GFAP-stained radial glial fibers
      showed that the radial fibers were consistently oriented in the direction of
      neuronal migration in the control brains. However, in the irradiated brain, such
      radial fibers were crumpled in the lateral region, or were reduced markedly in
      number in some parts of the dorsal region. These results revealed that neuronal
      migratory pathways (radial glial fibers) were destroyed differently in different
      regions, and that X-rays killed some cells including radial glial cells or their
      precursors during the embryonic stage. These effects of radiation on the
      developing brain may result from the possibility that neurogenetic time is
      different or there are cellular mechanisms involved in the radiosensitivity among
      different regions.

PMID- 10209248
TI  - Ponto-geniculo-occipital-wave suppression amplifies lateral geniculate nucleus
      cell-size changes in monocularly deprived kittens.
AB  - We have previously shown that during the post-natal critical period of
      development of the cat visual system, 1 week of instrumental rapid eye movement
      (REM) sleep deprivation (IRSD) during 2 weeks of monocular deprivation (MD)
      results in significant amplification of the effects of solely the 2-week MD on
      cell-size in the binocular segment of the lateral geniculate nucleus (LGN)
      [36,40]. In this study, we examined whether elimination of ponto-geniculo
      occipital (PGO)-wave phasic activity in the LGN during REM sleep (REMS), rather
      than suppression of all REMS state-related activity, would similarly yield
      enhanced plasticity effects on cell-size in LGN. PGO-activity was eliminated in
      LGN by bilateral pontomesencephalic lesions [8,32]. This method of removing
      phasic activation at the level of the LGN preserved sleep and wake proportions as
      well as the tonic activities (low voltage, fast frequency ECoG and low amplitude
      EMG) that characterize REM sleep. The lesions were performed in kittens on post
      natal day 42, at the end of the first week of the 2-week period of MD, the same
      age when IRSD was started in the earlier study. LGN interlaminar cell-size
      disparity increased in the PGO-wave-suppressed animals as it had in behaviorally
      REM sleep-deprived animals. Smaller A1/A-interlaminar ratios reflect the
      increased disparity effect in both the REM sleep- and PGO-suppressed groups
      compared to animals subjected to MD-alone. With IRSD, the effect was achieved
      because the occluded eye-related, LGN A1-lamina cells tended to be smaller
      relative to their size after MD-alone, whereas after PGO-suppressing lesions, the
      A1-lamina cells retained their size and the non-occluded eye-related, A-lamina
      cells tended to be larger than after MD-alone. Despite this difference, for which
      several possible explanations are offered, these A1/A-interlaminar ratio data
      indicate that in conjunction either with suppression of the whole of the REMS
      state or selective removal of REM sleep phasic activity at the LGN, altered
      visual input evokes more LGN cell plasticity during the developmental period than
      it would otherwise. These data further support involvement of the REM sleep state
      in reducing susceptibility to plasticity changes and undesirable variability in
      the course of normative CNS growth and maturation.

PMID- 10209249
TI  - CRBP I and CRABP I localisation during olfactory nerve development.
AB  - Retinoic acid appears to play a role during the formation of the olfactory
      system. Immunohistochemistry was used to localise the cellular retinoid binding
      proteins for retinol (CRBP I) and retinoic acid (CRABP I) in the embryonic and
      adult olfactory system. Our results indicate that RA produced by the CRBP I
      expressing 'glia-like' cells may act as a neurotrophic factor for the CRABP I
      expressing immature olfactory axons.

PMID- 10209250
TI  - Kir 4.1 channel expression in neuroblastomaxglioma hybrid NG108-15 cell line.
AB  - To study a possible involvement of inwardly rectifying K+ 4.1 (Kir 4. 1) channels
      in neural cell development, RT-PCR, immunocytochemistry and whole-cell patch
      clamp techniques were used to assess expression of Kir 4.1 channels in
      proliferating and differentiated NG108-15 cells. RT-PCR revealed co-expression of
      Kir 4.1 and rat ether-a-go-go-related gene (R-ERG) mRNAs in both proliferating
      and differentiated cells. The relative Kir 4.1 mRNA concentration increased
      markedly as cells progressed from undifferentiated to differentiated cells. Kir
      4.1-immunoreactivity was barely detectable in undifferentiated cells, but clearly
      detected in differentiated cells, indicating that Kir 4.1 gene and protein
      expressions are developmentally regulated. However, corresponding Kir 4.1 current
      could not be detected in differentiated cells using whole-cell patch-clamp
      recording. The 'silent' channel/receptor, often found in tumor cells, may carry
      genetic defects, which prevent functional expression of the channel. NG108-15 may
      serve as unique model for studying the relationship between the expression of an
      ion channel gene and the electrophysiological phenotype it encodes.

PMID- 10209251
TI  - Increased insulin-like growth factor-I (IGF-I) expression during early postnatal
      development differentially increases neuron number and growth in medullary nuclei
      of the mouse.
AB  - Morphometric analyses of the medulla were performed in transgenic mice that
      overexpress insulin-like growth factor-I (IGF-I) postnatally and in non
      transgenic littermates. The total volume of the medulla was increased in
      transgenic mice at all postnatal ages studied: 14 days (18%), 21 days (23%), 28
      days (23%), and 35 days (27%). By 35 days of age, the volumes of individual
      medullary nuclei were also increased: nucleus of the tractus solitarius (NTS,
      59%), dorsal motor nucleus of the vagus (DMV, 84%), hypoglossal nucleus (HN, 29%)
      and facial nucleus (FN, 21%). Neuron number in transgenic mice was significantly
      greater in NTS (50%) and DMV (53%), but not in the HN or the FN. Motor neurons in
      DMV, HN and FN of transgenic mice exhibited increases in mean profile areas of
      the soma and decreased numerical densities, suggesting increases in neuritic
      outgrowth. These results point to IGF-I actions in promoting neuron survival and
      growth, and suggest that IGF-I has differential effects on distinct neuron
      populations, possibly depending upon its time of expression.

PMID- 10209252
TI  - Dentate granule cell modulation in freely moving rats: vigilance state effects.
AB  - Dentate granule cell population responses to paired-pulse stimulation applied to
      the perforant pathway across a range of interpulse intervals (IPIs) were examined
      during different vigilance states-quiet waking (QW), slow-wave sleep (SWS), and
      rapid-eye movement (REM) sleep-in freely moving rats at 15, 30 and 90 days of
      age. Using these evoked field potentials, the paired-pulse index (PPI), a measure
      of the type and degree of modulation of dentate granule cell excitability, was
      computed and shown to be altered as a function of age. Animals, 15 days old,
      showed significantly lower levels of early inhibition (20-40 ms IPIs), i.e.,
      greater PPI values, during all three vigilance states when compared to both the
      30- and 90-day old animals. Adult, i.e, 90-day old animals, on the other hand,
      showed significantly greater levels of late inhibition (300-1000 ms IPIs), i.e.,
      lower PPI values, than the younger animals (15- and 30-day old) during QW and
      SWS. These results indicate that as the dentate field of the hippocampal
      formation matures there are significant alterations in the modulation of dentate
      granule cell activity.

PMID- 10209254
TI  - Function and biological applications of catalytic nucleic acids.

PMID- 10209253
TI  - Expression of receptor tyrosine kinase RYK in developing rat central nervous
      system.
AB  - Receptor tyrosine kinase RYK is a mammalian homologue of Drosophila Lio, which is
      involved in learning and memory and in axon guidance. We cloned a rat ryk gene
      and characterized its expression pattern in the central nervous system. Northern
      blot analysis of the whole brain revealed that the RYK mRNA was abundant during
      the period from 13 to 18 embryonic days (E13-18) and it decreased by E20. In the
      postnatal brain, the RYK signal was higher in postnatal one week (P1W) cerebrum
      and in P2W cerebellum than in later stages. In situ hybridization revealed that
      RYK was expressed throughout the central nervous system, mainly in the
      ventricular zone on E11 and E13. On E18 and E20, the remarkable level of RYK mRNA
      was detected in the ventricular zone as well as in the cortical plate of the
      forebrain. These two regions overlapped the immunoreactive areas of nestin and
      MAP2, a neural stem cell marker and a mature neural marker, respectively.
      Moreover, the double-labeling analysis showed that the same cells expressed both
      RYK and nestin in the ventricular zone. In the postnatal brain, RYK was
      predominantly expressed in neurons of various regions. These observations suggest
      that RYK plays a contributory role as a multifunctional molecule in the
      differentiation and maturation of neuronal cells in the central nervous system.

PMID- 10209255
TI  - Calcium ions as efficient cofactor of polycation-mediated gene transfer.
AB  - We investigated the effect of calcium on the transfection of non-viral DNA
      transfer systems. Cationic proteins such as the nuclear protein H1, the
      polycation polylysine and a number of commercial transfection agents exhibited
      high transfection rates in the presence of Ca2+. Without Ca2+ H1 and HMG1 were
      inactive in transfection of the human permanent endothelial cell line ECV 304
      while cationic liposomes such as Lipofectin and Lipofectamine did not show any
      Ca2+ dependence. More detailed experiments showed that Ca2+ was replaceable by
      the lysosomotropic agent chloroquine. Furthermore, it was possible to separate
      the transfection-enhancing role of Ca2+ from the actual transfection process by
      adding Ca2+ to the cells after the transfection period and still to obtain a
      significant transgene expression. This makes it possible to distinguish between
      cellular uptake of H1 (or mediator)-DNA complexes and endocytotic release. We
      also replaced soluble Ca2+ by Ca-phosphate precipitates not containing DNA and
      obtained similar transfection results. This allowed us to suggest that the
      addition of free Ca2+ to the transfection medium resulted in nascent Ca-phosphate
      microprecipitates. The known fusogenic and membranolytic activity of such
      microprecipitates could facilitate the transport through and the release of the
      transfecting complexes from the endosomal/lysosomal compartment.

PMID- 10209256
TI  - Regulation of cAMP responsive element binding modulator isoforms in cultured rat
      ovarian granulosa cells.
AB  - A pituitary glycoprotein hormone FSH stimulates ovarian granulosa cells to induce
      ovarian follicular development. In this study we identified rat ovarian genes
      that were rapidly induced by FSH in the cultured rat granulosa cells by means of
      subtraction cloning. Complementary DNA clones encoding cAMP responsive element
      binding modulator (CREM) were identified as one of the FSH inducible genes.
      Northern blotting and reverse transcription and polymerase chain reaction (RT
      PCR) analyses revealed that only the repressor type of CREM gene products, ICER
      (inducible cAMP early repressor) isoforms, were induced by FSH treatment in
      cultured rat granulosa cells. The induction of ICER by FSH was mimicked by
      reagents known to increase intracellular cAMP levels, indicating that the
      induction is through cAMP and protein kinase A signal transduction system.
      Induction of ICER was also confirmed as the protein levels. Electrophoretic
      mobility shift assay of granulosa cell extracts with a radiolabeled double
      stranded oligonucleotide corresponding to somatostatin cAMP responsive element
      also revealed that only the ICER proteins were induced by FSH treatment, whereas
      levels of CREM proteins were nearly constant regardless of the FSH treatment. Our
      present study demonstrates that FSH-induced and cAMP-mediated induction and
      attenuation of transcriptional responses by CREM gene products may be a key
      mechanistic component for the granulosa cell differentiation and proliferation.

PMID- 10209258
TI  - Mitosis enhances transgene expression of plasmid delivered by cationic liposomes.
AB  - A critical requirement of gene therapy is expression of the delivered transgene.
      Transgene expression is facilitated by access to the transcription mechanism
      found primarily in the nucleus. Factors modulating the interactions between
      intracellular plasmid and nuclear access are not well understood. In this study,
      the effect of mitosis on transgene expression was examined by quantitative flow
      cytometry. Transfection of HeLa cells synchronized at late G1 phase or G2/M phase
      was performed using a liposomal vector containing 1,2-dioleoyl-3
      trimethylammonium-propane (DOTAP) and dioleoyl-phosphatidylethanolamine (DOPE)
      (1:1 mol/mol). Cell samples were transfected and subsequently maintained in G1
      phase for various durations to modulate the time between plasmid entry and
      mitosis. The plasmid contains the sequence for a mutated green fluorescent
      protein (GFP(S65T)) that was used to examine transgene expression. Ethidium
      monoazide-labeled plasmid was employed to examine the association of plasmid with
      the cell membrane. The percentage of cells expressing GFP(S65T) increased sharply
      as the synchronized cell population passed through M phase, suggesting that an
      event associated with mitosis is essential for transgene expression. Expression
      levels of the transgene then declined 18 h after mitosis irrespective of
      transfection strategy. All transfection strategies resulted in the same maximum
      percentage of GFP(S65T) positive cells (40%) and average GFP(S65T) expression
      level (3.14x106 molecules per positive cell). Association of plasmid with the
      cell membrane at late G1 phase was 1.5-fold of that at G2/M phase. These data are
      evidence for control of transgene expression triggered by events associated with
      cell cycle.

PMID- 10209257
TI  - Isoforms of the human PDZ-73 protein exhibit differential tissue expression.
AB  - Patients with renal and colon cancer frequently develop IgG autoantibodies toward
      the NY-CO-38/PDZ-73 antigen, a protein of 652 amino acids (73 kDa) which contains
      three copies of the PDZ protein-protein interaction domain. The gene encoding PDZ
      73 mapped to chromosome 11p15.4-p15.1. Additional tissue-specific isoforms were
      identified: PDZ-45, which lacks the third PDZ domain and the putative PEST
      protein degradation motif, is expressed in kidney, colon, small intestine, brain
      and testis; PDZ-54 and PDZ-59, which also lack the third PDZ domains, have unique
      carboxyl terminal amino acids and are expressed in brain, kidney, bladder, colon
      cancer and renal cancer; and a putative PDZ-37 isoform, containing only the third
      PDZ domain, that is expressed in the central nervous system. Immunohistochemical
      staining with anti-PDZ 73 monoclonal antibodies showed strong cytoplasmic
      reactivity in epithelial cells of the small intestine, colon and kidney tubules,
      with a prominent apical staining pattern in cells of the small intestine. The
      reactivity pattern of the antibodies with various tissues correlated with the
      mRNA expression pattern of the PDZ-45 isoform. The existence of multiple PDZ-73
      isoforms with variations in tissue distribution, PDZ domains, protein degradation
      sequences and carboxyl terminal structure indicate that these isoforms have
      distinct tissue-specific functions.

PMID- 10209259
TI  - Cloning and expression of the transferrin and ferritin genes in a marsupial, the
      brushtail possum (Trichosurus vulpecula).
AB  - Transferrin and ferritin cDNAs have been isolated and characterised from the
      common brushtail possum (Trichosurus vulpecula), the first marsupial examples of
      these genes. The transferrin cDNA encodes a 711 amino acid pre-protein which
      shows high levels of amino acid identity with eutherian transferrins (58-60%) and
      lactoferrins (54-56%). Phylogenetic analysis suggests that the possum transferrin
      has evolved independently along a pathway distinct from that of the eutherian
      transferrins and lactoferrins. Possum H-ferritin is a 182 residue protein which
      shares 86-94% amino acid identity with mammalian, avian and amphibian sequences.
      Ferritin mRNA was detected in all tissues tested, whereas transferrin was highly
      expressed in possum liver and mammary gland, and at lower levels in heart, testis
      and lung. In the possum mammary gland, ferritin mRNA was expressed throughout
      lactation with higher levels during the first 30 days which coincides with the
      high iron concentration of milk at this time. The transferrin gene was
      differentially expressed during lactation with peak mRNA levels detected during
      the first 6 days of lactation and after day 106 throughout late lactation. The
      pattern of transferrin mRNA expression in the mammary gland was identical to that
      of another whey protein, the late lactation protein, suggesting that the
      transcription of these genes may be regulated by a similar mechanism in this
      tissue.

PMID- 10209260
TI  - RT-PCR cloning, characterization and mRNA expression analysis of a cDNA encoding
      a type II asparagine synthetase in common bean.
AB  - Following a RT-PCR strategy based on the design of degenerate oligonucleotides
      resembling conserved domains of asparagine synthetase (AS; EC 6.3.5.4), we
      isolated a 2 kb cDNA clone (PVAS2) from root tissue of the common bean (Phaseolus
      vulgaris). PVAS2 encodes a protein of 584 amino acids with a predicted relative
      molecular mass of 65810 Da, an isoelectric point of 6.4, and a net charge of -7.2
      at pH 7.0. The amino acid sequence of the protein encoded by PVAS2 is very
      similar to that encoded by the soybean SAS2 asparagine synthetase gene. The amino
      terminal residues of the predicted PVAS2 protein are identical to the amino acids
      that constitute the glutamine-binding (GAT) domain of AS from other plant
      species, which suggests that the PVAS2 cDNA encodes a type II glutamine-dependent
      form of asparagine synthetase. Southern blot analysis indicates that the common
      bean AS is part of a small family composed of at least two genes. Expression
      analysis by Northern blot revealed that the PVAS2 transcript accumulates to a
      high level in roots and, to a lesser extent, in nodules and developing pods.
      Accumulation of the PVAS2 transcript in the root seems to be negatively regulated
      by light and sucrose, and positively regulated by nitrate.

PMID- 10209261
TI  - Oligonucleotide inhibition of the interaction of HIV-1 Tat protein with the trans
      activation responsive region (TAR) of HIV RNA.
AB  - The interaction of HIV-1 Tat protein with its recognition sequence, the trans
      activation responsive region TAR is a potential target for drug discovery against
      HIV infection. We show by use of an in vitro competition filter binding
      interference assay that synthetic oligodeoxyribonucleotides complementary to the
      HIV-1 TAR RNA apical stem-loop and bulge region inhibit the binding of Tat
      protein or a Tat peptide (residues 37-72) better than two small molecules that
      have been shown to bind TAR RNA, Hoechst 33258 and neomycin B. The inhibition is
      not sensitive to length between 13 and 16 residues or precise positioning but
      shorter oligonucleotides are less effective. Enhanced inhibition was obtained for
      a 16-mer 2'-O-methyl oligoribonucleotide but not for C5-propyne pyrimidine
      substituted oligonucleotides. Control non-antisense oligonucleotides were
      occasionally also effective in filter binding interference but only the
      complementary antisense 2'-O-methyl oligoribonucleotide was effective in gel
      mobility shift assays in direct TAR binding or in interference with Tat peptide
      binding to the TAR stem-loop. This is the first demonstration of effective
      inhibition of the Tat-TAR interaction by nuclease-stabilized oligonucleotide
      analogues.

PMID- 10209262
TI  - A Caenorhabditis elegans wee1 homolog is expressed in a temporally and spatially
      restricted pattern during embryonic development.
AB  - A wee1 homolog, wee-1.1, is expressed in both a temporally and spatially
      restricted pattern during early Caenorhabditis elegans embryogenesis, and is
      undetectable throughout the remainder of embryogenesis. The wee-1.1 message
      appears to be zygotically expressed in the somatic founder cell E of the 12-cell
      embryo. This expression disappears when the E blastomere divides for the first
      time. The wee-1.1 message then appears transiently in the nuclei of the eight
      great-granddaughter cells of the AB somatic founder cell, just before these cells
      divide in the 16-cell embryo. Following this division, the wee-1.1 mRNA is no
      longer detectable throughout the remainder of embryogenesis. The expression of
      wee-1.1 in the E blastomere and in the AB progeny appears to be restricted to
      nuclei in prophase and metaphase of the cell cycle. Analysis of the wee-1.1 mRNA
      expression pattern in maternal-effect lethal mutants suggests that this
      expression pattern is restricted to cells of the E and AB fates in the early
      embryo. This mRNA expression pattern is restricted to a 10-15-min span of
      embryonic development and may be regulating the timing of crucial cell divisions
      at this early stage of development.

PMID- 10209263
TI  - Transcriptional regulation of the squalene synthase gene (ERG9) in the yeast
      Saccharomyces cerevisiae.
AB  - The ergosterol biosynthetic pathway is a specific branch of the mevalonate
      pathway. Since the cells requirement for sterols is greater than for isoprenoids,
      sterol biosynthesis must be regulated independently of isoprenoid biosynthesis.
      In this study we explored the transcriptional regulation of squalene synthase
      (ERG9) in Saccharomyces cerevisiae, the first enzyme dedicated to the synthesis
      of sterols. A mutant search was performed to identify genes that were involved in
      the regulation of the expression of an ERG9-lacZ promoter fusion. Mutants with
      phenotypes consistent with known sterol biosynthetic mutations (ERG3, ERG7,
      ERG24) increased expression of ERG9. In addition, treatment of wild-type cells
      with the sterol inhibitors zaragozic acid and ketoconazole, which target squalene
      synthase and the C-14 sterol demethylase respectively, also caused an increase in
      ERG9 expression. The data also demonstrate that heme mutants increased ERG9
      expression while anaerobic conditions decreased expression. Additionally, the
      heme activator protein transcription factors HAP1 and HAP2/3/4, the yeast
      activator protein transcription factor yAP-1, and the phospholipid transcription
      factor complex INO2/4 regulate ERG9 expression. ERG9 expression is decreased in
      hap1, hap2/3/4, and yap-1 mutants while ino2/4 mutants showed an increase in ERG9
      expression. This study demonstrates that ERG9 transcription is regulated by
      several diverse factors, consistent with the idea that as the first step
      dedicated to the synthesis of sterols, squalene synthase gene expression and
      ultimately sterol biosynthesis is highly regulated.

PMID- 10209264
TI  - Higher induction of heat shock protein 72 by heat stress in cisplatin-resistant
      than in cisplatin-sensitive cancer cells.
AB  - Induction of the heat shock proteins (HSPs) is involved in the increased
      resistance to cancer therapies such as chemotherapy and hyperthermia. We used two
      human ovarian cancer cell lines; a cisplatin (CDDP)-sensitive line A2780 and its
      CDDP-resistant derivative, A2780CP. The concentration of intracellular
      glutathione (GSH) is higher (2.7-fold increase) in A2780CP cells than in A2780
      cells. A mild treatment with a heat stress (42 degrees C for 30 min) induced
      synthesis of both the heat shock protein 72 (Hsp72) mRNA and the HSP72 protein in
      A2780CP cells, but not in A2780 cells. In contrast, a severe heat stress (45
      degrees C for 30 min) increased synthesis of the HSP72 protein in the two cell
      lines. The induced level of the HSP72 protein by the severe treatment was higher
      in A2780CP than in A2780 cells. The gel mobility shift assay showed that DNA
      binding activities of the heat shock factor (HSF) in the two cell lines were
      induced similarly and significantly by the mild heat stress. Immunocytochemistry
      using an anti HSF1 antibody also indicated that mild heat stress activated the
      HSF1 translocation from the cytosol to the nucleus similarly in the both cell
      lines. Pretreatment of CDDP-sensitive A2780 cells with N-acetyl-L-cysteine, a
      precursor of GSH, effectively enhanced induction of the Hsp72 mRNA by the mild
      heat stress. The present findings demonstrate that induction of the Hsp72 mRNA by
      the mild heat stress was more extensive in CDDP-resistant A2780CP cells. It is
      likely that the higher GSH concentration in A2780CP cells plays an important role
      in promoting Hsp72 gene expression induced by the mild heat stress probably
      through processes downstream of activation of HSF-DNA binding.

PMID- 10209265
TI  - Promoter structure of mouse RANKL/TRANCE/OPGL/ODF gene.
AB  - Receptor activator of NF-kappa B ligand (RANKL)/tumor necrosis factor-related
      activation induced cytokine (TRANCE)/osteoprotegerin ligand (OPGL)/osteoclast
      differentiation factor (ODF) is a membrane-bound signal transducer responsible
      for differentiation and maintenance of osteoclasts. To elucidate the mechanism
      regulating RANKL/TRANCE/OPGL/ODF gene expression, we cloned the 5'-flanking basic
      promoter region of the mouse RANKL/TRANCE/OPGL/ODF gene and characterized it by
      transient transfection studies and genomic Southern blot analysis. Inverted TATA-
      and CAAT-boxes and a putative Cbfa1/Osf2/AML3 binding domain constituted the
      basic promoter structure. The repeated half-sites for the vitamin D3 (VitD3) and
      glucocorticoid receptors were located at -935 and -640, respectively. Transient
      transfection studies revealed that short-term treatment with 1alpha,25(OH)2 VitD3
      or dexamethasone increased luciferase activity up to 204% and 178%, respectively;
      on the other hand, treatment with dibutyryl cyclic AMP did not affect the
      promoter activity. Since the expression of Cbfa1/Osf2/AML3 is also regulated by
      VitD3, 1alpha,25(OH)2 VitD3 might affect RANKL/TRANCE/OPGL/ODF gene expression
      both directly and indirectly. CpG methylation was observed dominantly in mouse
      stromal cells, ST2, of a later passage which ceased to support in vitro
      osteoclastogenesis, suggesting that the methylation status of the CpG loci in the
      RANKL/TRANCE/OPGL/ODF gene promoter may be one of the influential cis-regulating
      factors.

PMID- 10209266
TI  - Identification and analysis of the promoter region of the human NeuroD-related
      factor (NDRF)1.
AB  - We isolated and characterized the human NeuroD-related factor (NDRF)/NeuroD2/KW8
      gene. The NDRF gene consisted of two exons and one intron. NDRF had one
      transcriptional starting point, and in its 5'-flanking region, no TATA box was
      detected, but 16 E boxes (CANNTG) were present. RNA blotting analysis revealed
      that HIT-T15 and D283 cells expressed a 3.3 kb band of the NDRF transcript.
      Promoter analysis by luciferase assay demonstrated that luciferase activity
      changed between -120 and -195, and between -451 and -564, both regions wherein a
      single E box existed. Radiation hybrid mapping showed that NDRF linked the marker
      SHGC-36242 with a LOD score of 8.53 and was located on 17q12-22.

PMID- 10209267
TI  - Molecular cloning of LMO41, a new human LIM domain gene.
AB  - We have identified a new human LIM domain gene by isolating an autoantigenic cDNA
      clone from a human breast tumor cDNA library. The predicted amino acid sequence
      of the cDNA clone's 495 bp open reading frame contains two tandem LIM domain
      motifs, and within the LIM domain region there is 62% identity with the analogous
      region of the LIM-only gene LMO1. The homology to LMO1 is restricted to the 360
      bp region encoding the tandemly repeated LIM domains, the rest of the open
      reading frame as well as the extensive, GC-rich 5' untranslated region, and 3'
      region of the 2 kb cDNA sequence are unrelated to any known genes. This gene has
      been designated LMO4.

PMID- 10209268
TI  - Molecular cloning and functional characterization of two alternatively spliced
      Ntcp isoforms from mouse liver1.
AB  - To isolate the murine Na+/taurocholate cotransporting polypeptide (Ntcp), we
      screened a mouse liver cDNA library and identified Ntcp1, encoding a 362 amino
      acid protein and Ntcp2, encoding a 317 amino acid protein which had a shorter C
      terminal end. Both isoforms mediated saturable Na+-dependent transport of
      taurocholate when expressed in Xenopus laevis oocytes. Analysis of the gene
      revealed that Ntcp2 is produced by alternative splicing where the last intron is
      retained.

PMID- 10209269
TI  - Molecular cloning and sequencing of cDNAs encoding homologues of human Ku70 and
      Ku80 autoantigen from Xenopus and their expression in various Xenopus tissues.
AB  - We isolated cDNA clones encoding Ku70 and Ku80 homologues of Xenopus laevis from
      a cDNA library prepared from Xenopus oocytes. The nucleotide sequences of these
      Ku70 and Ku80 homologues have coding sequences of 1833 bp and a 611 aa protein,
      and 2178 bp and a 726 aa protein, respectively. The amino acid sequences deduced
      from the open reading frame of the Ku70 and Ku80 cDNA clones were highly
      homologous to those from Ku genes previously isolated, such as human (ca. 65% and
      ca. 62% identity, respectively) and mouse (ca. 65% and ca. 60%), and show a
      certain degree of homology to Drosophila (ca. 27% with Ku70), Caenorhabditis
      elegans (ca. 20% with Ku80) and Saccharomyces cerevisiae (ca. 23% and ca. 19%).
      Our detailed comparison of the predicted amino acid sequences among these species
      revealed the highly conserved octa-peptide LPFXXDIR common to both Xenopus Ku70
      and Ku80 homologues in the region showing the high homology throughout the
      species tested. A Northern analysis using specific cDNA probes showed that Ku
      poly(A)+ mRNAs are expressed at high levels in Xenopus adult oocyte and testis.

PMID- 10209270
TI  - Cloning of mouse sepiapterin reductase gene and characterization of its promoter
      region.
AB  - We have isolated and characterized approximately 5 kb mouse sepiapterin reductase
      gene (Spr) and a highly homologous pseudogene (Sprp). The authentic Spr gene is
      present as a single copy in the mouse genome and is composed of three exons
      containing the entire coding region. The primer extension experiment located the
      transcription initiation site in a putative pyrimidine-rich Inr element. The
      promoter region of the Spr gene is embedded within a CpG island. It was shown
      that the promoter region is devoid of distinctive TATA and CAAT boxes. Transient
      transfection of a series of 5' deletion derivatives of the Spr promoter showed
      the sequence between -83 and -51 to be essential for promoter activity. The
      pseudogene Sprp lacks promoter region and exon 3.

PMID- 10209271
TI  - Molecular cloning and expression of Xenopus laevis requiem cDNA1.
AB  - Requiem is an apoptosis-associated gene, which was originally identified in mouse
      (T.G. Gabig et al., J. Biol. Chem. 269 (1994) 29515-29519). In this study, we
      isolated five independent cDNA clones for frog Requiem (xReq) from Xenopus laevis
      ovary. Sequence analysis of the multiple cDNAs has suggested that Xenopus genome
      contains at least two non-allelic copies of the xReq gene. The amino acid
      sequence deduced from the cDNAs contained a single Kruppel-type zinc-finger motif
      and two PHD-finger motifs. Northern analysis revealed that the ovary expressed
      xReq transcripts with different sizes.

PMID- 10209272
TI  - Isolation and characterization of the gene encoding the mouse broad specificity
      lysosomal alpha-mannosidase1.
AB  - A genomic clone encoding the mouse lysosomal alpha-mannosidases was isolated and
      the gene was found to be encoded by 24 exons spanning approximately 14.5 kb of
      genomic DNA. The intron-exon boundaries were conserved between the mouse, human,
      and bovine lysosomal alpha-mannosidase genes as well as being partially conserved
      in several other species. In order to define the promoter of the mouse
      mannosidase gene, >1 kb of DNA sequence was obtained upstream from the respective
      initiation codon. The transcription start site was identified by a 5'-RACE
      procedure and putative promoter elements were identified by expression of
      promoter/reporter constructs. Fluorescence in situ hybridization analysis using
      the mouse and human mannosidase genomic clones as probes, localized the mouse
      gene to chromosome 8, at band position 8C2, and the human gene to chromosome
      19p13.2, a region syntenic to the lysosomal mannosidase gene on mouse chromosome
      8.

PMID- 10209273
TI  - Multiple folding pathways for heterologously expressed human prion protein.
AB  - Human PrP (residues 91-231) expressed in Escherichia coli can adopt several
      conformations in solution depending on pH, redox conditions and denaturant
      concentration. Oxidised PrP at neutral pH, with the disulphide bond intact, is a
      soluble monomer which contains 47% alpha-helix and corresponds to PrPC.
      Denaturation studies show that this structure has a relatively small, solvent
      excluded core and unfolds to an unstructured state in a single, co-operative
      transition with a DeltaG for folding of -5.6 kcal mol-1. The unfolding behaviour
      is sensitive to pH and at 4.0 or below the molecule unfolds via a stable folding
      intermediate. This equilibrium intermediate has a reduced helical content and
      aggregates over several hours. When the disulphide bond is reduced the protein
      adopts different conformations depending upon pH. At neutral pH or above, the
      reduced protein has an alpha-helical fold, which is identical to that observed
      for the oxidised protein. At pH 4 or below, the conformation rearranges to a fold
      that contains a high proportion of beta-sheet structure. In the reduced state the
      alpha- and beta-forms are slowly inter-convertible whereas when oxidised the
      protein can only adopt an alpha-conformation in free solution. The data we
      present here shows that the human prion protein can exist in multiple
      conformations some of which are known to be capable of forming fibrils. The
      precise conformation that human PrP adopts and the pathways for unfolding are
      dependent upon solvent conditions. The conditions we examined are within the
      range that a protein may encounter in sub-cellular compartments and may have
      implications for the mechanism of conversion of PrPC to PrPSc in vivo. Since the
      conversion of PrPC to PrPSc is accompanied by a switch in secondary structure
      from alpha to beta, this system provides a useful model for studying major
      structural rearrangements in the prion protein.

PMID- 10209274
TI  - Fluorescein monophosphates as fluorogenic substrates for protein tyrosine
      phosphatases.
AB  - A series of novel fluorescein monophosphates aimed as substrates for protein
      tyrosine phosphatases (PTPs) were synthesized and evaluated against fluorescein
      diphosphate (FDP), the currently used fluorescent substrate for PTPs. In contrast
      to FDP, which is dephosphorylated to monophosphate and then to fluorescein in a
      sequential reaction, these monophosphates are dephosphorylated in a single step.
      This eliminates the complication in assaying PTPs due to the cleavage of the
      second phosphate group. The kinetic studies of these substrates with PTPs were
      performed and Michaelis-Menten parameters were obtained. These designed
      substrates have Km 0.03-0. 35 mM, kcat/Km of 3-100 mM-1 s-1 with CD45 and PTP1B.
      The results showed that the substrates with negative charge groups on the
      fluorescein have higher affinities for PTP1B, which are consistent with other
      observations. In this series, fluorescein monosulfate monophosphate (FMSP) was
      the best substrate observed. Since FMSP showed large increases in both absorption
      and fluorescence upon dephosphorylation by PTPs at pH>6.0, it is one of the most
      sensitive, stable and high affinity substrates reported for PTPs.

PMID- 10209275
TI  - Protein movement during complex-formation between tissue plasminogen activator
      and plasminogen activator inhibitor-1.
AB  - Plasminogen activator inhibitor-1 (PAI-1) rapidly inactivates tissue plasminogen
      activator (tPA). After initial binding and cleavage of the reactive-centre loop
      of PAI-1, this complex is believed to undergo a major rearrangement. Using
      surface plasmon resonance and SDS-PAGE, we have studied the influence of a panel
      of monoclonal antibodies on the reaction leading to the final covalent complex.
      On the basis of these data, we suggest the mechanisms for the action of different
      classes of inhibitory antibodies. We propose that the antibodies which convert
      PAI-1 into a substrate for tPA do this by means of preventing the conversion of
      the initial PAI-1/tPA complex into the final complex by sterical intervention.
      Moreover, the localisation of the binding epitopes on free PAI-1, as well as on
      the PAI-1/tPA complex, suggests that tPA in the final complex cannot be located
      near helices E and F, as has previously been proposed.

PMID- 10209276
TI  - Influence of different types of effectors on the kinetic parameters of suicide
      inactivation of catalase by hydrogen peroxide.
AB  - The effects of cyanide and azide ions (class A), sodium-n-dodecyl sulphate (SDS)
      and 2-mercaptoethanol (class B), 3-aminotriazole (class C) and NADPH (class D) on
      the initial activity (ai), inactivation rate constant (ki) and the partition
      ratio (r) of bovine liver catalase reaction with its suicide substrate, hydrogen
      peroxide, were studied in 50 mM sodium phosphate buffer, pH 7.0 at 27 degrees C.
      The above kinetic parameters were determined by processing the progress curve
      data. In class A, which contains fast and reversible inhibitors of catalase, a
      proportional decrease in ai and ki was observed by inhibitors, so that the r
      remained constant. In class B, which contains slow and irreversible inactivators,
      a decrease in ai and constancy of ki and r were observed when catalase was
      incubated in the presence of such inactivators for a determined time. In class C,
      containing effector which can combine with intermediate compound I, ai was
      relatively unchanged but an increase in ki and a decrease in r were observed. In
      class D, containing effector which reduces compound I to ferricatalase, ai was
      not affected significantly but some decrease in ki was detected which was linked
      with an increase in r. These results demonstrate that different classes of
      effectors affect the determined kinetic parameters of catalase in various ways.
      Thus, determination of such parameters by simple kinetic experiments can be
      carried out for classification of the agents which have an effect on the kinetics
      of catalase.

PMID- 10209278
TI  - Reactions of prostaglandin endoperoxide synthase with hydroperoxide and reducing
      substrates under single turnover conditions.
AB  - The peroxidase reaction of prostaglandin endoperoxide synthase was investigated
      by transient state kinetics using stoichiometric amounts of substrates. The rate
      constants for the conversion of compound I to intermediate II determined with a
      stoichiometric amount of hydroperoxide were found to be lower by an order of
      magnitude than when an excess of hydroperoxide was used. The difference was
      attributed to ability of the compound I of prostaglandin endoperoxide synthase to
      be reduced by the excess of hydroperoxide. This suggests that the true rate
      constant of unimolecular conversion compound I to intermediate II at 3 degrees C
      is 5-10 s-1 instead of 50-200 s-1 as reported before. The latter value rather
      characterizes the combined process of spontaneous and hydroperoxide-dependent
      transformation of compound I. Stoichiometric amounts of reducing substrates
      significantly stimulated transformation of compound I. This effect could not be
      entirely explained by their reducing action, which was measured by following the
      oxidation kinetics. The results of the global fit of the experimental data
      suggest that reducing substrates, in addition to their direct action in reducing
      compound I to compound II, indirectly stimulate transformation of compound I to
      the tyrosyl radical form of intermediate II, thereby stimulating the
      cyclooxygenase reaction.

PMID- 10209277
TI  - Comparison of physical chemical properties of llama VHH antibody fragments and
      mouse monoclonal antibodies.
AB  - Antigen specific llama VHH antibody fragments were compared to antigen specific
      mouse monoclonal antibodies with respect to specificity, affinity and stability.
      The llama VHH antibody fragments and the mouse monoclonal antibodies investigated
      were shown to be highly specific for the protein antigen hCG or the hapten
      antigen RR-6. The affinity of the interaction between monovalent llama VHH
      antibody fragments and their antigen is close to the nanomolar range, similar to
      the bivalent mouse monoclonal antibodies studied. Llama VHH antibody fragments
      are similar to mouse monoclonal antibodies with respect to antigen binding in the
      presence of ammonium thiocyanate and ethanol. The results show that relative to
      antigen specific mouse monoclonal antibodies, antigen specific llama VHH
      fragments are extremely temperature stable. Two out of six llama VHHs are able to
      bind antigen specifically at temperatures as high as 90 degrees C, whereas four
      out of four mouse monoclonal antibodies are not functional at this temperature.
      Together with the finding that llama VHH fragments can be produced at high yield
      in Saccharomyces cerevisiae, these findings indicate that in the near future
      antigen specific llama VHH fragments can be used in for antibodies unexpected
      products and processes.

PMID- 10209279
TI  - Effects of high pressure and temperature on the wild-type and F29W mutant forms
      of the N-domain of avian troponin C.
AB  - The N-domain of troponin C (residues 1-90) regulates muscle contraction through
      conformational changes induced by Ca2+ binding. A mutant form of the isolated
      domain of avian troponin C (F29W) has been used in previous studies to observe
      conformational changes that occur upon Ca2+ binding, and pressure and temperature
      changes. Here we set out to determine whether the point mutation itself has any
      effects on the protein structure and its stability to pressure and temperature in
      the absence of Ca2+. Molecular dynamics simulations of the wild-type and mutant
      protein structures suggested that both structures are identical except in the
      main chain and the loop I region near the mutation site. Also, the simulations
      proposed that an additional cavity had been created in the core of the mutant
      protein. To determine whether such a cavity would affect the behavior of the
      protein when subjected to high pressures and temperatures, we performed 1H-NMR
      experiments at 300, 400, and 500 MHz on the wild-type and F29W mutant forms of
      the chicken N-domain troponin C in the absence of Ca2+. We found that the mutant
      protein at 5 kbar pressures had a destabilized beta-sheet between the Ca2+
      binding loops, an altered environment near Phe-26, and reduced local motions of
      Phe-26 and Phe-75 in the core of the protein, probably due to a higher
      compressibility of the mutant. Under the same pressure conditions, the wild-type
      domain exhibited little change. Furthermore, the hydrophobic core of the mutant
      protein denatured at temperatures above 47 degrees C, while the wild-type was
      resistant to denaturation up to 56 degrees C. This suggests that the partially
      exposed surface mutation (F29W) significantly destabilizes the N-domain of
      troponin C by altering the packing and dynamics of the hydrophobic core.

PMID- 10209280
TI  - Cathepsin D from the liver of the antarctic icefish Chionodraco hamatus exhibits
      unusual activity and stability at high temperatures1.
AB  - Cathepsin D was purified to homogeneity from the liver of Antarctic icefish by
      anion-exchange chromatography followed by affinity chromatography on concanavalin
      A Sepharose. The purified enzyme showed a molecular mass of 40 kDa and displayed
      optimal activity at pH 3.0 with a synthetic chromogenic substrate. The N-terminal
      sequence of this proteinase was determined by automated Edman degradation and was
      used to design a primer for use in reverse-transcriptase polymerase chain
      reaction. The open reading frame of the cloned cDNA encoded an aspartic
      proteinase, which contained the experimentally determined N-terminal sequence.
      The predicted sequence (396 residues) had a high similarity with those of
      cathepsin D from various vertebrate sources, but was considerably different from
      that of nothepsin, a distinct aspartic proteinase described previously from
      Antarctic fish [1]. Determination of kinetic parameters for substrate hydrolysis
      showed that, at temperatures between 8 and 50 degrees C, the icefish cathepsin D
      had a higher specificity constant (kcat/Km) than human cathepsin D. The stability
      of both enzymes was measured at 50 degrees C and half-lives of 55 and 3 min were
      derived for icefish and human cathepsin D, respectively.

PMID- 10209281
TI  - Drosophila lebanonensis alcohol dehydrogenase: pH dependence of the kinetic
      coefficients.
AB  - The alcohol dehydrogenase (ADH) from Drosophila lebanonensis shows 82% positional
      identity to the alcohol dehydrogenases from Drosophila melanogaster. These insect
      ADHs belong to the short-chain dehydrogenase/reductase family which lack metal
      ions in their active site. In this family, it appears that the function of zinc
      in medium chain dehydrogenases has been replaced by three amino acids, Ser138,
      Tyr151 and Lys155. The present work on D. lebanonensis ADH has been performed in
      order to obtain information about reaction mechanism, and possible differences in
      topology and electrostatic properties in the vicinity of the catalytic residues
      in ADHs from various species of Drosophila. Thus the pH dependence of various
      kinetic coefficients has been studied. Both in the oxidation of alcohols and in
      the reduction of aldehydes, the reaction mechanism of D. lebanonensis ADH in the
      pH 6-10 region was consistent with a compulsory ordered pathway, with the
      coenzymes as the outer substrates. Over the entire pH region, the rate limiting
      step for the oxidation of secondary alcohols such as propan-2-ol was the release
      of the coenzyme product from the enzyme-NADH complex. In the oxidation of ethanol
      at least two steps were rate limiting, the hydride transfer step and the
      dissociation of NADH from the binary enzyme-NADH product complex. In the
      reduction of acetaldehyde, the rate limiting step was the dissociation of NAD+
      from the binary enzyme-NAD+ product complex. The pH dependences of the kon
      velocity curves for the two coenzymes were the opposite of each other, i.e. kon
      increased for NAD+ and decreased for NADH with increasing pH. The two curves
      appeared complex and the kon velocity for the two coenzymes seemed to be
      regulated by several groups in the free enzyme. The kon velocity for ethanol and
      the ethanol competitive inhibitor pyrazole increased with pH and was regulated
      through the ionization of a single group in the binary enzyme-NAD+ complex, with
      a pKa value of 7.1. The kon velocity for acetaldehyde was pH independent and
      showed that in the enzyme-NADH complex, the pKa value of the catalytic residue
      must be above 10. The koff velocity of NAD+ appeared to be partly regulated by
      the catalytic residue, and protonation resulted in an increased dissociation
      rate. The koff velocity for NADH and the hydride transfer step was pH
      independent. In D. lebanonensis ADH, the pKa value of the catalytic residue was
      0.5 pH units lower than in the ADHS alleloenzyme from D. melanogaster. Thus it
      can be concluded that while most of the topology of the active site is mainly
      conserved in these two distantly related enzymes, the microenvironment and
      electrostatic properties around the catalytic residues differ.

PMID- 10209282
TI  - Purification, properties and enhanced expression under nitrogen starvation of the
      NADP+-isocitrate dehydrogenase from the cyanobacterium Phormidium laminosum.
AB  - Nitrogen starvation enhances up to 8-fold the cellular level of the NADP+
      dependent isocitrate dehydrogenase activity (isocitrate:NADP+ oxidoreductase
      (decarboxylating), IDH, EC 1.1.1.42) in the thermophilic filamentous non-N2
      fixing cyanobacterium Phormidium laminosum. The enzyme was purified 650-fold to
      electrophoretic homogeneity from nitrogen-starved cells with an activity yield of
      25% and a specific activity of 500 U (mg protein)-1. The native enzyme showed a
      pI of 5.9 and it was a dimer of 107 kDa consisting of two identical subunits of
      53 kDa. The activity required the presence of a divalent metal cation as an
      essential activator, Mn2+ or Mg2+ being the most effective. The optimum
      temperature for activity was 55 degrees C and the Ea for catalysis was 39.7 kJ
      mol-1. An optimum pH for activity of 8.5 was found and the calculated pKE1, pKE2
      and pKES1 of enzyme ionisation groups were 6.0, 8.9 and 6.3, respectively. Km
      values of 22, 50 and 24 microM were calculated for d,l-isocitrate, NADP and Mn2+,
      respectively, in the Mn2+-dependent reaction and 70, 32 and 159 microM for d,l
      isocitrate, NADP and Mg2+, respectively, in the Mg2+-dependent reaction. The
      decarboxylating activity was inhibited by ATP, ADP and by its reaction products 2
      oxoglutarate and NADPH2. Polyclonal antibodies raised against the pure IDH were
      used to assess the presence of the enzyme in cells subjected to nitrogen
      starvation.

PMID- 10209283
TI  - Hydrolysis of emulsified mixtures of triacylglycerols by pancreatic lipase.
AB  - Hydrolysis of the emulsified mixture of short-chain triacylglycerols by porcine
      pancreatic lipase in the presence of procolipase and micellar sodium
      taurodeoxycholate has been studied. Increase in the content of tributyrin and
      trioctanoin in the mixture with triacetin had highly cooperative effects on the
      formation of the interfacial lipase procolipase complex. Abrupt enhancement of
      the complex stability was observed in the presence of 0.4-0.6 mol mol-1 of
      tributyrin or 0.58 mol mol-1 of trioctanoin in the substrate phase. The affinity
      of lipase towards interfacially bound procolipase for the trioctanoin containing
      0.07-0.42 mol mol-1 of triacetin was approximately three times higher than that
      for pure trioctanoin. The cooperative processes involved in complex formation did
      not contribute to the affinity of the interfacial lipase/(pro)colipase complex
      towards substrate molecules and its catalytic activity.

PMID- 10209284
TI  - Candidacidal activity prompted by N-terminus histatin-like domain of human
      salivary mucin (MUC7)1.
AB  - Histidine-rich peptides (histatins, Hsn) in saliva are thought to provide a non
      immune defense against Candida albicans. Sequence homology search of the human
      salivary mucin, MUC7, against histatins revealed a domain at the N-terminus (R3
      Q17) having 53% identity to Hsn-5. To determine its candidacidal activity, this
      15 residue basic histidine-rich domain of MUC7 (I) was prepared by solid-phase
      Fmoc chemistry. Various N- and C-terminal protected derivatives of I were also
      synthesized to correlate the effect of peptide overall charge in exhibiting cidal
      potency. Candidacidal activity measurement of I and its variants showed
      considerable ED50 values (effective dosage required to kill 50% of candida
      cells), albeit greater than Hsn-5 (ED50 approximately 4-6 microM). Of the various
      analogs tested, N-terminal free acid (I, ED50 approximately 40 microM) and amide
      (V, ED50 approximately 16 microM) exhibited appreciable candidacidal activities
      suggesting the possible role of peptide net charge in cidal action. Blocking of N
      terminus with a bulky octanoyl group showed only marginal effect on the cidal
      activity of I or V, indicating that hydrophobicity of these synthetic constructs
      may not be important for exerting such activities. Membrane-induced
      conformational transition from random coil to helical structures of all the test
      peptides implied their tendency to adapt order structures at the lipid-membrane
      interface similar to that of Hsn-5. However, comparison of propensity for helical
      structure formation vs. ED50 indicated that cidal potency of MUC7 Hsn-like
      peptides depends largely on electrostatic interactions irrespective of secondary
      structural elements. Delineation of solution structure of the most active peptide
      (V) by 2D-NMR revealed essentially a non-structured conformation in aqueous
      medium, which further supported the fact that the peptide helical structure may
      not be a prerequisite for posing candidacidal activity. The formation of smaller
      truncated peptides and/or Hsn-like fragments on proteolytic degradation of intact
      MUC7 in the presence of oral flora provided indirect evidence that mucin could
      serve as a backup candidacidal agent to salivary Hsn.

PMID- 10209285
TI  - Conformation, pH-induced conformational changes, and thermal unfolding of anti
      p24 (HIV-1) monoclonal antibody CB4-1 and its Fab and Fc fragments.
AB  - Conformation, acid-induced conformational changes and stability of the murine
      monoclonal antibody CB4-1 directed against the human immunodeficiency virus type
      1 capsid protein p24, and its Fab and Fc fragments, were analysed by circular
      dichroism (CD), fluorescence, and differential scanning calorimetry (DSC)
      measurements. CD spectra show the characteristics expected for beta-proteins.
      Lowering the pH to 3.5 reduces the stability, but does not change the
      conformation. Between pH 3.5 and 2.0 conformational changes and the formation of
      new structures are indicated. Deconvolution of the bimodal DSC curves of CB4-1
      reveals five 'two-state' transitions at pH 7.5. At pH 5 and below, only four
      transitions are found. Half transition temperatures Tm and molar enthalpy changes
      DeltaHm gradually decrease at pH 4 and 3.4. At pH 2.1, two low-temperature
      (Tm=36.9 and 44.1 degrees C) and two high-temperature (Tm=74.6 and 76.8 degrees
      C) transitions are identified. The Fab and Fc fragments behave similarly.
      Deconvolution of their monophasic DSC curves yields two 'two-state' transitions
      for each fragment. Tm and DeltaHm values gradually decrease at pH 4.0 and 3.4;
      and at pH 2.1 and 2.8 for Fab and Fc, respectively, one of the transitions is
      found at high temperature (Tm=67.2 and 75.9 degrees C for Fab and Fc,
      respectively).

PMID- 10209286
TI  - The role of the non-conserved residue at position 104 of class A beta-lactamases
      in susceptibility to mechanism-based inhibitors.
AB  - The role of the non-conserved amino acid residue at position 104 of the class A
      beta-lactamases, which comprises a highly conserved sequence of amino acids at
      the active sites of these enzymes, in both the hydrolysis of beta-lactam
      substrates and inactivation by mechanism-based inhibitors was investigated. Site
      directed mutagenesis was performed on the penPC gene encoding the Bacillus cereus
      569/H beta-lactamase I to replace Asp104 with the corresponding Staphylococcus
      aureus PC1 residue Ala104. Kinetic data obtained with the purified Asp104Ala B.
      cereus 569/H beta-lactamase I was compared to that obtained from the wild-type B.
      cereus and S. aureus enzymes. Replacement of amino acid residue 104 had little
      effect on the Michaelis parameters for the hydrolysis of both S- and A-type
      penicillins. Relative to wild-type enzyme, the Asp104Ala beta-lactamase I had 2
      fold higher Km values for benzylpenicillin and methicillin, but negligible
      difference in Km for ampicillin and oxacillin. However, kcat values were also
      slightly increased resulting in little change in catalytic efficiency, kcat/Km.
      In contrast, the Asp104Ala beta-lactamase I became more like the S. aureus enzyme
      in its response to the mechanism-based inhibitors clavulanic acid and 6-beta
      (trifluoromethane sulfonyl)amido-penicillanic acid sulfone with respect to both
      response to the inhibitors and subsequent enzymatic properties. Based on the
      known three-dimensional structures of the Bacillus licheniformis 749/C,
      Escherichia coli TEM and S. aureus PC1 beta-lactamases, a model for the role of
      the non-conserved residue at position 104 in the process of inactivation by
      mechanism-based inhibitors is proposed.

PMID- 10209287
TI  - Amino acid residues of heparin cofactor II required for stimulation of thrombin
      inhibition by sulphated polyanions.
AB  - A variety of sulphated polyanions in addition to heparin and dermatan sulphate
      stimulate the inhibition of thrombin by heparin cofactor II (HCII). Previous
      investigations indicated that the binding sites on HCII for heparin and dermatan
      sulphate overlap but are not identical. In this study we determined the
      concentrations (IC50) of various polyanions required to stimulate thrombin
      inhibition by native recombinant HCII in comparison with three recombinant HCII
      variants having decreased affinity for heparin (Lys-173-->Gln), dermatan sulphate
      (Arg-189-->His), or both heparin and dermatan sulphate (Lys-185-->Asn). Pentosan
      polysulphate, sulphated bis-lactobionic acid amide, and sulphated bis-maltobionic
      acid amide resembled dermatan sulphate, since their IC50 values were increased to
      a much greater degree (>/=8-fold) by the mutations Arg-189-->His and Lys-185-
      >Asn than by Lys-173-->Gln (</=1.5-fold). By contrast, the IC50 values for
      fucosylated chondroitin sulphate, chondroitin sulphate E, dextran sulphate, and
      fucoidan were minimally affected. Only in the case of heparin was the IC50
      increased to a greater degree by both Lys-173-->Gln and Lys-185-->Asn (>/=6-fold)
      than by Arg-189-->His (</=1.5-fold). None of the polyanions significantly
      stimulated inhibition of thrombin by an N-terminal deletion mutant of HCII
      (Delta1-74). These results suggest that, like dermatan sulphate and heparin,
      other polyanions stimulate HCII primarily by an allosteric mechanism requiring
      the N-terminal acidic domain.

PMID- 10209288
TI  - Cloning, expression and biochemical characterization of a basic-acidic hybrid
      phospholipase A2-II from Agkistrodon halys pallas.
AB  - A cDNA encoding a basic-acidic hybrid phospholipase A2-II from Agkistrodon halys
      Pallas with an N-terminus highly homologous to that of BPLA2 and a C-terminus
      sequence almost the same as that of APLA2 was inserted into a bacterial
      expression vector and effectively expressed in Escherichia coli RR1. The protein
      was produced as insoluble inclusion bodies. After partial purification by
      washing, the inclusion bodies with Triton X-100, denaturing and refolding, the
      renatured recombinant protein was purified by FPLC column superose 12. The
      purified recombinant enzyme with an isoelectric point of pH 6.8 could cross-react
      with antiserum prepared against acidic phospholipase A2. The enzymatic activity
      of the expressed basic-acidic hybrid phospholipase A2-II is close to that of
      denatured-refolded native basic phospholipase A2, and has the same inhibiting
      effect on platelet aggregation as denatured-refolded acidic phospholipase A2, but
      lacks the hemolytic activity of denatured-refolded basic phospholipase A2. To
      study the structural relationships among basic phospholipase A2, acidic
      phospholipase A2 and basic-acidic hybrid phospholipase A2-II, molecular modeling
      of basic-acidic hybrid phospholipase A2-II was done. The roles of various amino
      acid residues in the enzymatic activity and pharmacological activities of
      phospholipase A2 are discussed.

PMID- 10209289
TI  - Crotonobetaine reductase from Escherichia coli consists of two proteins.
AB  - Crotonobetaine reductase from Escherichia coli is composed of two proteins
      (component I (CI) and component II (CII)). CI has been purified to
      electrophoretic homogeneity from a cell-free extract of E. coli O44 K74. The
      purified protein shows l(-)-carnitine dehydratase activity and its N-terminal
      amino acid sequence is identical to the caiB gene product from E. coli O44 K74.
      The relative molecular mass of CI has been determined to be 86100. It is composed
      of two identical subunits with a molecular mass of 42600. The isoelectric point
      of CI was found to be 4.3. CII was purified from an overexpression strain in one
      step by ion exchange chromatography on Fractogel EMD TMAE 650(S). The N-terminal
      amino acid sequence of CII shows absolute identity with the N-terminal sequence
      of the caiA gene product, i.e. of the postulated crotonobetaine reductase. The
      relative molecular mass of the protein is 164400 and it is composed of four
      identical subunits of molecular mass 41500. The isoelectric point of CII is 5.6.
      CII contains non-covalently bound FAD in a molar ratio of 1:1. In the
      crotonobetaine reductase reaction one dimer of CI associates with one tetramer of
      CII. A still unknown low-molecular-mass effector described for the l(-)-carnitine
      dehydratase is also necessary for crotonobetaine reductase activity. Monoclonal
      antibodies were raised against the two components of crotonobetaine reductase.

PMID- 10209290
TI  - Porcine odorant-binding protein: structural stability and ligand affinities
      measured by fourier-transform infrared spectroscopy and fluorescence
      spectroscopy.
AB  - Infrared spectra show that the binding of the odorants 2-isobuthyl-3
      methoxypyrazine (PYR) and 3,7-dimethyl-1-octanol (DMO) stabilises the tertiary
      structure of porcine OBP-I against thermal denaturation. The fluorescence
      emission spectrum of the single tryptophan shows a lambdamax at 337 nm,
      indicating that the residue is not directly exposed to the solvent. Tryptophan
      does not appear to be involved in the odorant binding process and it is not
      accessible to the fluorescence quenchers NaI, CsCl and acrylamide. The binding of
      the fluorescent dye 1-aminoanthracene (1-AMA), a strong ligand, does not modify
      the tryptophan fluorescence spectrum. In contrast, the lambdamax of 1-AMA bound
      to OBP-I is shifted from 537 to 481 nm, with a lambdamax intensity increase by a
      factor of 80. Bound 1-AMA is displaced by odorant molecules in competitive
      binding assays and can be employed in simple and rapid binding assay, avoiding
      the use of radioactive ligands. The Scatchard plot shows that 1-AMA binds to OBP
      I with a dissociation constant of 1.3 microM and an equimolar stoichiometry.

PMID- 10209291
TI  - Characterization of toad liver glutathione transferase.
AB  - The major form of glutathione transferase from the toad liver previously designed
      as Bufo bufo liver GST-7.6 (A. Aceto, B. Dragani, T. Bucciarelli, P. Sacchetta,
      F. Martini, S. Angelucci, F. Amicarelli, M. Miranda and C. Di Ilio, Biochem. J.
      289 (1993) 417-422) has been characterized. According to its partial amino acid
      sequence, the toad enzyme may be included in the pi class GST and named bbGST P2
      2. However, bbGST P2-2 appears to be immunologically, structurally and
      kinetically distinct from any other members of pi family, including bbGST P1-1,
      suggesting that it may constitute a subset of pi class GST. The data support the
      hypothesis that the transition from aquatic to terrestrial life causes a switch
      of the GST amphibian pattern promoting the expression of a GST form (bbGST P2-2)
      able to counteract, with higher efficiency, the toxic effects of reactive
      metabolites of oxidative metabolism and those of hydrophobic xenobiotics.

PMID- 10209292
TI  - A novel 35 kDa frog liver acid metallophosphatase.
AB  - The lower molecular weight (35 kDa) acid phosphatase from the frog (Rana
      esculenta) liver is a glycometalloenzyme susceptible to activation by reducing
      agents and displaying tartrate and fluoride resistance. Metal chelators (EDTA,
      1,10-phenanthroline) inactivate the enzyme reversibly in a time- and temperature
      dependent manner. The apoenzyme is reactivated by divalent transition metal
      cations, i. e. cobalt, zinc, ferrous, manganese, cadmium and nickel to 130%, 75%,
      63%, 62%, 55% and 34% of the original activity, respectively. Magnesium, calcium,
      cupric and ferric ions were shown to be ineffective in this process. Metal
      analysis by the emission spectrometry method (inductively coupled plasma-atomic
      emission spectrometry) revealed the presence of zinc, iron and magnesium. The
      time course of the apoenzyme reactivation, the stabilization effect and the
      relatively high resistance to oxidizing conditions indicate that the zinc ion is
      crucial for the enzyme activity. The presence of iron was additionally confirmed
      by the visible absorption spectrum of the enzyme with a shoulder at 417 nm and by
      the electron paramagnetic resonance line of high spin iron(III) with geff of 2.4.
      The active center containing only zinc or both zinc and iron ions is proposed.
      The frog liver lower molecular weight acid phosphatase is a novel
      metallophosphatase of lower vertebrate origin, distinct from the mammalian
      tartrate-resistant, purple acid phosphatases.

PMID- 10209294
TI  - Structural characterization, stability and fatty acid-binding properties of two
      French genetic variants of human serum albumin.
AB  - Four bisalbuminemic, unrelated persons were found in Bretagne, France, and their
      variant and normal albumins were isolated by DEAE ion exchange chromatography,
      reduced, carboxymethylated and treated with CNBr. Comparative two-dimensional
      electrophoresis of the CNBr digests showed that three of the variants were
      modified in fragment CB4, whereas the fourth had an abnormal fragment CB1. These
      fragments were isolated, digested with trypsin and mapped by reverse-phase HPLC.
      Sequencing of altered tryptic peptides showed that the three variants modified in
      CB4 were caused by the same, previously unreported, amino acid substitution:
      Asp314-->Val (albumin Brest). The fourth, however, was a proalbumin variant with
      the change Arg-2-->Cys (albumin Ildut). Both amino acid substitutions can be
      explained by point mutations in the structural gene: GAT-->GTT (albumin Brest)
      and CGT-->TGT (albumin Ildut). The proalbumin Ildut is very unstable and already
      in vivo it is to a large extent cleaved posttranslationally to Arg-Albumin and
      normal albumin. Furthermore, we observed that during a lengthy isolation
      procedure the remaining proalbumin was changed to Arg-Albumin or proalbumin
      lacking Arg-6. In addition, part of normal albumin had lost Asp1. Gas
      chromatographic investigations using isolated proteins indicated that albumin
      Brest has improved in vivo fatty acid-binding properties, whereas the structural
      modification(s) of albumin Ildut does not affect fatty acid binding.

PMID- 10209293
TI  - Purification of beef kidney D-aspartate oxidase overexpressed in Escherichia coli
      and characterization of its redox potentials and oxidative activity towards
      agonists and antagonists of excitatory amino acid receptors.
AB  - The flavoenzyme d-aspartate oxidase from beef kidney (DASPO, EC 1.4. 3.1) has
      been overexpressed in Escherichia coli. A purification procedure, faster than the
      one used for the enzyme from the natural source (bDASPO), has been set up
      yielding about 2 mg of pure recombinant protein (rDASPO) per each gram of wet E.
      coli paste. rDASPO has been shown to possess the same general biochemical
      properties of bDASPO, except that the former contains only FAD, while the latter
      is a mixture of two forms, one active containing FAD and one inactive containing
      6-OH-FAD (9-20% depending on the preparation). This results in a slightly higher
      specific activity (about 15%) for rDASPO compared to bDASPO and in facilitated
      procedures for apoprotein preparation and reconstitution. Redox potentials of -97
      mV and -157 mV were determined for free and l-(+)-tartrate complexed DASPO,
      respectively, in 0.1 M KPi, pH 7.0, 25 degrees C. The large positive shift in the
      redox potential of the coenzyme compared to free FAD (-207 mV) is in agreement
      with similar results obtained with other flavooxidases. rDASPO has been used to
      assess a possible oxidative activity of the enzyme towards a number of compounds
      used as agonists or antagonists of neurotransmitters, including d-aspartatic
      acid, d-glutamic acid, N-methyl-d-aspartic acid, d,l-cysteic acid, d-homocysteic
      acid, d, l-2-amino-3-phosphonopropanoic acid, d-alpha-aminoadipic acid, d
      aspartic acid-beta-hydroxamate, glycyl-d-aspartic acid and cis-2, 3-piperidine
      dicarboxylic acid. Kinetic parameters for each substrate in 50 mM KPi, pH 7.4, 25
      degrees C are reported.

PMID- 10209295
TI  - The role of the P2' position of Bowman-Birk proteinase inhibitor in the
      inhibition of trypsin. Studies on P2' variation in cyclic peptides encompassing
      the reactive site loop.
AB  - The role of the P2' residue in proteinase inhibitors of the Bowman-Birk family
      was investigated using synthetic cyclic peptides based on the reactive site loop
      of the inhibitor. A series of 21 variants having different P2' residues was
      tested for inhibition of trypsin, and the rate at which they were hydrolysed by
      this enzyme was also measured. Variation at P2' was found to result in marked
      differences in inhibitory potency, with the best sequence (Ile) having a Ki value
      of 9 nM. Peptides with P2' Gly, Pro or Glu failed to demonstrate any measurable
      inhibition (Ki>1 mM). The peptides also displayed significant differences in the
      rates at which they were hydrolysed, which varied by over three orders of
      magnitude between the difference sequences. There was found to be overall
      correlation between the Ki value and the rate of hydrolysis, with peptides that
      inhibited best also being hydrolysed more slowly. The results are discussed in
      light of the sequence information for Bowman-Birk inhibitor proteins.

PMID- 10209296
TI  - The individual tyrosines of proteins: their spectra may or may not differ from
      those in water or other solvents.
AB  - The overall derivative spectrum of a protein is the sum of the individual
      derivative spectra just as the overall ultraviolet spectrum of a protein is the
      sum of its component parts. The RNase and DNA binding protein Sso7d has two
      tyrosines and one tryptophan. We used two mutant forms of the protein to show
      that the individual aromatics contribute derivative spectra that can be explained
      on the basis of their environments. We used mutant forms of iso-1-cytochrome c to
      estimate the contributions of the single tryptophan and three of the five
      tyrosines to the overall derivative spectrum. The tryptophan spectrum is not
      exceptional. The comparable tyrosine spectra are more complex. The derivative
      spectrum of individual tyrosines does not correspond to that expected on the
      basis of concentration. This is a reflection of two factors: (1) the extent to
      which mutations are sensed distally through the introduction and compression of
      packing defects; and (2) the extent to which electronic transitions of tyrosine
      are influenced by nearby atoms. This influence could take the form of tyrosine
      residing in an area where the dielectric coefficient is not uniform; it could
      also result from tyrosine bumping into neighboring atoms with lower frequency
      than it does in solution.

PMID- 10209297
TI  - Molecular characterisation of a novel thermophilic nitrile hydratase.
AB  - The thermophilic soil isolate, Bacillus pallidus Dac521, expresses a constitutive
      nitrile hydratase. The purified enzyme was found to be a 110 kDa tetramer
      composed of two alpha and two beta subunits with molecular masses of 27 kDa and
      29 kDa, respectively. The enzyme electrophoresed as a single protein band on
      native PAGE but two protein bands with isoelectric points of 4.7 and 5.5 on
      isoelectric focusing suggested the presence of isozymes. The purified enzyme was
      moderately thermostable up to 55 degrees C and the enzyme activity was stable
      over a broad pH range. Comparisons of the N-terminal amino acid sequences of the
      nitrile hydratase subunits with those of other nitrile hydratases showed up to
      90% identity for the beta subunit sequence but no significant identity for the
      alpha subunit. The enzyme hydrolysed a narrow range of aliphatic substrates and
      did not hydrolyse any of the cyclic, hydroxy-, di- or aromatic nitriles tested.
      The activity was irreversibly inhibited by the aromatic nitrile, benzonitrile.
      The kinetic constants for acetonitrile, acrylonitrile and propionitrile compared
      favourably with those of mesophilic nitrile hydratases.

PMID- 10209298
TI  - The location of active site opening and closing events in the prehydride transfer
      phase of the oxidative deamination reaction catalyzed by bovine liver glutamate
      dehydrogenase using a novel pH jump approach.
AB  - A pH jump approach has been developed and used to locate the opening and closing
      events occurring in the time course of the beef liver glutamate dehydrogenase
      catalyzed reaction. A comparison of the pH jump results, the resolved component
      time courses, and the 340 nm fluorescence signal suggests the existence and
      location on the reaction time course of a previously unreported prehydride
      transfer complex.

PMID- 10209299
TI  - The human homolog of Drosophila cornichon protein is differentially expressed in
      alloactivated T-cells.
AB  - To identify novel genes induced in the early stage of T-cell activation, mRNA
      expression in alloactivated human lymphocytes was examined. Differential display
      reverse transcription PCR analysis revealed a 207-bp cDNA fragment which was
      upregulated 24 h after allostimulation of a human T-cell line. The corresponding
      complete 1396 bp cDNA, named TGAM77, encodes a predicted 134 amino acid protein
      which shares 63% homology with the cornichon (cni) protein of Drosophila
      melanogaster. Upregulation of TGAM77 mRNA in the early phase of T-cell activation
      was confirmed by Northern blot and RT-PCR analysis of activated human
      lymphocytes. TGAM77 mRNA is expressed in a variety of human tissues with various
      expression levels. In analogy to cni which is involved in an epidermal growth
      factor-like signaling pathway inducing cellular asymmetry in Drosophila
      oogenesis, TGAM77 might function in similar signaling establishing vectorial re
      localization and concentration of signaling events in T-cell activation.

PMID- 10209300
TI  - Isolation of spermidine synthase gene (spsA) of Dictyostelium discoideum.
AB  - The gene encoding spermidine synthase (spsA) was isolated from Dictyostelium
      discoideum using the technique of insertional mutagenesis. Northern blot analysis
      showed that the spsA mRNA is expressed maximally during the vegetative stage and
      decreases gradually during the 24 h of development. Sequencing of the genomic DNA
      and a full-length cDNA clone indicated the presence of one intron in a gene
      coding for a predicted protein (SpsA) with 284 amino acids. The sequence is
      highly conserved, with amino acid identities compared to spermidine synthases of
      humans, 59.5%, to mouse, 61.3%, and to yeast, 58.1%. A null mutant of the spsA
      gene is unable to grow in the absence of exogenous spermidine. Development of
      spsA null cells grown in the absence of spermidine produced fruiting bodies that
      have abnormally short stalks.

PMID- 10209301
TI  - Association of TGF-beta signaling in angiotensin II-induced PAI-1 mRNA
      upregulation in mesangial cells: role of PKC.
AB  - This study aimed to identify the intracellular signaling pathway in angiotensin
      II (Ang II)-induced upregulation of plasminogen activator inhibitor type 1 (PAI
      1) mRNA expression in cultured rat glomerular mesangial cells, and to examine the
      interaction between Ang II and TGF-beta signaling. Ang II-induced upregulation of
      PAI-1 mRNA expression was prevented by a protein kinase C (PKC) inhibitor,
      bisindorylmaleimide I. While phorbol 12-myristate 13-acetate (PMA) upregulated
      the PAI-1 mRNA expression, a calcium ionophore, ionomycin, had little effect.
      Mesangial cells pretreated with PMA for 24 h to downregulate PKC demonstrated
      attenuated response to Ang II. A protein tyrosine kinase inhibitor, genistein,
      completely blocked both Ang II- and PMA-induced PAI-1 mRNA expression.
      Transforming growth factor-beta1 (TGF-beta1) alone induced the expression, and in
      the presence of Ang II, TGF-beta1 superinduced PAI-1 mRNA expression to a higher
      extent. Both bisindorylmaleimide I and genistein suppressed the Ang II plus TGF
      beta1-induced PAI-1 mRNA upregulation to the basal level, while downregulation of
      PKC attenuated the synergistic upregulation of PAI-1 mRNA expression to the level
      comparable to TGF-beta1 alone. These data suggest that, in rat mesangial cells,
      (1) PKC and protein tyrosine kinase(s) are involved in the Ang II signaling
      cascade, (2) protein tyrosine kinase(s) works downstream from PKC in the cascade,
      and (3) there is an interaction between the Ang II and TGF-beta signal pathways
      downstream from PKC. In in vivo settings, local activation of renin-angiotensin
      and TGF-beta systems in the glomeruli may synergistically augment PAI-1
      expression, promote mesangial matrix accumulation and progression of glomerular
      injury.

PMID- 10209302
TI  - Effect of tumor necrosis factor-alpha on insulin signal transduction in rat
      adipocytes: relation to PKCbeta and zeta translocation.
AB  - Although much evidence has been accumulated suggesting that tumor necrosis factor
      alpha (TNF-alpha) is an important mediator of insulin resistance, the precise
      mechanism involved is still unclear. Recently, it has been reported that insulin
      induced glucose uptake is mediated by activation of second messengers such as
      insulin receptor substrate 1 (IRS-1), phosphatidylinositol 3-kinase (PI3K), and
      diacylglycerol (DG)-protein kinase C (PKC). We have examined the effect of TNF
      alpha on insulin-induced glucose uptake and activations of tyrosine kinase, IRS
      1, PI3K and PKC in rat adipocytes. Pretreatment with 0.1-100 nM TNF-alpha for 60
      min resulted in a significant decrease in 10 nM insulin- or 1 microM 12-O
      tetradecanoyl phorbol-13-acetate (TPA)-induced [3H]2-deoxyglucose uptake without
      affecting basal glucose uptake. 10 nM insulin-stimulated activation of tyrosine
      kinase, IRS-1 and PI3K was suppressed by preincubation with 0.1-10 nM TNF-alpha
      for 60 min. 10 nM TNF-alpha pretreatment also suppressed 10 nM insulin- and 1
      microM TPA-induced increases in membrane-associated PKCbeta and PKCzeta.
      Furthermore, 10 nM TNF-alpha, by itself, altered PKCbeta translocation from the
      membrane to cytosol. These results suggest that TNF-alpha inhibits insulin
      stimulated activation of both the tyrosine kinase-IRS-1-PI3K-PKCzeta pathway and
      DG-PKC pathway. Finally, TNF-alpha contributes to insulin resistance in rat
      adipocytes.

PMID- 10209303
TI  - Ibd1p, a possible spindle pole body associated protein, regulates nuclear
      division and bud separation in Saccharomyces cerevisiae.
AB  - The proper spatial and temporal coordination of mitosis and cytokinesis is
      essential for maintaining genomic integrity. We describe the identification and
      characterization of the Saccharomyces cerevisiae IBD1 gene, which encodes a novel
      protein that regulates the proper nuclear division and bud separation. IBD1 was
      identified by the limited homology to byr4, a dosage-dependent regulator of
      cytokinesis in Schizosaccharomyces pombe. IBD1 is not an essential gene, and the
      knock-out cells show no growth defects except for the reduced mating efficiency
      [1]. However, upon ectopic expression from an inducible promoter, IBD1 is lethal
      to the cell and leads to abnormal nuclear division and bud separation. In detail,
      approximately 90% of the IBD1 overexpressing cells arrest at large bud stages
      with dividing or divided nuclei. In some IBD1 overexpressing cells, spindle
      elongation and chromosome separation occur within the mother cell, leading to
      anucleated and binucleate daughter cells. The anucleated cell can not bud, but
      the binucleate cell proceeds through another cell cycle(s) to produce a cell with
      multiple nuclei and multiple buds. Observations of the F-actin and chitin rings
      in the IBD1 overexpressing cells reveal that these cells lose the polarity for
      bud site selection and growth or attain the hyper-polarity for growth. Consistent
      with the phenotypes, the IBD1 overexpressing cells contain a broad range of DNA
      content, from 2 to 4 N or more. A functional Ibd1p-GFP fusion protein localizes
      to a single dot at the nuclear DNA boundary in the divided nuclei or to double
      dots in dividing nuclei, suggesting its localization on the spindle pole body
      (SPB). The cross-species expressions of IBD1 in S. pombe and byr4 in S.
      cerevisiae cause defects in shape, implicating the presence of a conserved
      mechanism for the control of cytokinesis in eukaryotes. We propose that Ibd1p is
      an SPB associated protein that links proper nuclear division to cytokinesis and
      bud separation.

PMID- 10209304
TI  - Angiotensin II-mediated signal transduction events in cystic fibrosis pancreatic
      duct cells.
AB  - Different signal transduction pathways, i.e. Ca2+- and cAMP-dependent, involved
      in mediating the effects of angiotensin II (AII) were investigated separately
      using the short-circuit current (Isc) technique and radioimmunoassay (RIA) in a
      cystic fibrosis pancreatic cell line (CFPAC-1) which exhibits defective cAMP
      dependent but intact Ca2+-dependent anion secretion. The AII-induced Isc could be
      inhibited by the specific antagonist for AT1, losartan (1 microM), but not the
      antagonist for AT2, PD123177 (up to 10 microM). The AII-induced Isc was also
      reduced by the treatment of the cells with a Ca2+ chelator, BAPTA-AM (100
      microM), indicating a dependence of the AII-induced anion secretion on the
      intracellular Ca2+. Treatment of the cells with pertussis toxin (0.1 microg/ml)
      or a phospholipase C (PLC) inhibitor, U73122 (5 microM), resulted in a
      substantial reduction in the AII-induced Isc indicating involvement of Gi and PLC
      in the Ca2+-dependent anion secretion. RIA measurements showed that AII
      stimulated an increase in cAMP production which could be reduced by losartan,
      pertussis toxin and U73122 but not BAPTA-AM. In addition, inhibitors of
      cyclooxygenase, indomethacin (10 microM) and piroxicam (10 microM), did not have
      any effect on the AII-induced cAMP production, excluding the involvement of
      prostaglandins. Our results suggest that both AII-stimulated cAMP and Ca2+
      dependent responses are mediated by the AT1 receptor and Gi-coupled PLC pathway.
      However, the AII-stimulated cAMP production in CFPAC-1 cells is not dependent on
      Ca2+ or the formation of prostaglandins.

PMID- 10209305
TI  - Cyclic AMP induces inhibition of cyclin A expression and growth arrest in human
      hepatoma cells.
AB  - Classical cytotoxic therapy has been minimally useful in the treatment of
      hepatocellular carcinoma. In an effort to develop a new approach to the treatment
      of this neoplasm, we have investigated the signal transduction pathways
      regulating the growth of human hepatoma cells. In the data reported here, cyclic
      AMP (cAMP), a negative growth regulator for many cells of epithelial origin,
      induced G1 synchronization and apoptosis in the HepG2 human hepatoma cell line.
      The effects of cAMP on the components of the G1/S transition were analyzed. There
      was no detectable effect of two different cAMP analogs, 8-bromo cAMP or dibutyryl
      cAMP on the level of the D-type cyclins, cyclin E, cyclin-dependent kinase 2,
      cyclin-dependent kinase 4, p53, or the cyclin-dependent kinase inhibitors p21 or
      p27. In contrast, the cAMP analogs induced a dramatic downregulation of cyclin A
      protein, cyclin A messenger RNA, and cyclin A-dependent kinase activity. Cyclin A
      dependent kinase has been shown to be required for the G1-S transition.
      Furthermore, cyclin A deregulation has been implicated in the pathogenesis of
      hepatocellular carcinoma. The data reported here suggest a novel signal
      transduction-based approach to hepatoma therapy.

PMID- 10209306
TI  - Continuous phosphorylation of GAP-43 and MARCKS by long-term TPA treatment in SK
      N-SH human neuroblastoma cells.
AB  - Long-term treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) down
      regulates select protein kinase C (PKC) isozymes and may differentially affect
      PKC substrates. We investigated the role of PKC down-regulation on
      phosphorylation of two PKC substrates, the 43 kDa growth-associated protein (GAP
      43) and the myristoylated alanine-rich C-kinase substrate (MARCKS) in SK-N-SH
      human neuroblastoma cells. Cells were treated with 70 nM TPA for 15 min, 17 or 72
      h. Phosphorylation of MARCKS and GAP-43 was elevated throughout 72 h of TPA. The
      magnitude and peptidic sites of phosphorylation in GAP-43 and MARCKS were similar
      after all TPA treatments. GAP-43, but not MARCKS, content was increased after 17
      and 72 h of TPA. The ratio of GAP-43 phosphorylation to content was elevated
      throughout 17 h but returned to control by 72 h as content increased. PKC epsilon
      and alpha isozyme content was greatly reduced after 72 h of TPA but membranes
      retained 23% of PKC activity. Only PKC epsilon translocated to membranes after 15
      min TPA. GAP-43 content after 72 h of TPA was increased in subcellular fractions
      in which significant PKC epsilon isozyme concentration remained. These results
      demonstrate that continuous TPA differentially affected phosphorylation of PKC
      substrate proteins and regulation of PKC isozyme content in SK-N-SH cells.

PMID- 10209307
TI  - G-protein signalling pathways and oestrogen: a role of balanced maintenance in
      osteoblasts.
AB  - Oestrogen (E2) is an important regulator of bone cell function and alterations in
      oestrogen levels may cause abnormal bone metabolism in vivo. In this study we
      examined the long term effects of 17beta-oestradiol (17beta-E2) on G-proteins and
      the secondary signalling pathways of phospholipase C (PLC), cyclic adenosine
      monophosphate (cAMP), and 1,4,5-inositol triphosphate (IP3). Cells from neonatal
      mouse calvariae were cultured in phenol red-free RPMI 1640 medium supplemented
      with charcoal stripped foetal calf serum for 192 h with either oestrogen (10(-8)
      M), or oestrogen withdrawal after 48 h. Cultures were stimulated for the final 48
      h with IL-6 (10(-10) M), or left unstimulated. Western blot analysis was
      undertaken on osteoblast membrane preparations obtained by 10 mM Tris-HCl, 0.1 mM
      EDTA pH 7.8 and centrifugation at 40,000 x g for 2 h. For cAMP study, cells were
      stimulated with IL-6 for either 15 min or 30 min. Intracellular cAMP was
      extracted from cells and measured by ELISA methodology. For the IP3 assay, cells
      were stimulated with IL-6 for 20 s and IP3 levels measured using
      radioimmunoassay. The blots revealed increased levels of Gialpha-, and Gqalpha
      proteins with oestrogen withdrawal and IL-6 stimulation. This was in comparison
      to cells which were unstimulated, or stimulated with IL-6 with continuous 17beta
      E2, or IL-6 alone. Gsalpha expression decreased with oestrogen withdrawal
      compared to the control. Limited amounts of Gialpha-, Gsalpha-, and Gqalpha
      proteins were identified with continuous 17beta-E2. The levels of PLC isoforms
      PLCbeta1-2 were not affected by the differing oestrogen conditions. The cAMP
      production induced by IL-6 stimulation for 30 min and withdrawal of 17beta-E2 was
      lower and significantly different compared to the control study (P<0.05). Also IL
      6 activation with continuous oestradiol increased cAMP levels and was
      significantly different from the control cells (P<0.01). However, 17beta-E2 had
      no effect on the formation of intracellular IP3, although IL-6 significantly
      lowered IP3 levels in all the groups compared to the control (P<0.01). These
      results suggest that oestrogen modulates the signal transduction pathways of G
      protein molecules, and the secondary pathways of cAMP in mouse osteoblast-like
      cells.

PMID- 10209334
TI  - Nickel enhances telomeric silencing in Saccharomyces cerevisiae.
AB  - Certain nickel compounds including crystalline nickel sulfide (NiS) and
      subsulfide (Ni3S2) are potent human and animal carcinogens. In Chinese hamster
      embryo cells, an X-linked senescence gene was inactivated following nickel
      induced DNA methylation. Nickel also induced the inactivation of the gpt reporter
      gene by chromatin condensation and a DNA methylation process in a transgenic gpt+
      Chinese hamster cell line (G12), which is located near a heterochromatic region.
      To determine if nickel can cause gene silencing independently of DNA methylation,
      based only on the induction of changes in chromatin structure, we measured its
      effect on gene silencing in Saccharomyces cerevisiae. Growth of yeast in the
      presence of nickel chloride repressed a telomeric marker gene (URA3) and resulted
      in a stable epigenetic switch. This phenomenon was dependent on the number of
      cell doubling prior to selection and also on the distance of the marker gene from
      the end of the chromosome. The level of TPE (telomeric position effect) increased
      linearly with elevations of nickel concentration. Addition of magnesium inhibited
      this effect, but magnesium did not silence the reporter gene by itself. The level
      of silencing was also assessed following treatment with other transition metals:
      cobalt, copper and cadmium. In the sublethal range, cobalt induced similar
      effects as nickel, while copper and cadmium did not change the basal level of
      gene expression. Silencing by copper and cadmium were evident only at
      concentrations of those metals where the viability was very low.

PMID- 10209335
TI  - Use of cryopreserved peripheral mononuclear blood cells in biomonitoring.
AB  - This study was performed to investigate the effect of storing blood samples by
      freezing on selected biomarkers and possible implications for biomonitoring.
      Comparative measurements were performed in order to investigate the use of
      cryopreserved vs. freshly separated peripheral mononuclear blood cells (PMBC)
      obtained from donor blood. Measurements of DNA-repair, mutant frequency, and
      subcell content were included. Samples for large biomonitoring studies are
      usually taken from study groups within a short time period of days/weeks and
      storing of study material for later analysis can be necessary. We measured the
      DNA repair activity as dimethylsulfate induced unscheduled DNA synthesis (UDS) in
      PMBC incubated with either autologous plasma or fetal bovine serum (FBS).
      Comparison of the hprt mutant frequency by the T cell cloning assay was made in
      parallel. Finally the content of B/T-lymphocytes and monocytes was measured in
      phytohemaglutinin (PHA)-stimulated cultures at different time intervals. The
      results showed a higher DNA repair activity in cryopreserved samples compared
      with fresh samples. We also found differences in mutant frequencies with higher
      values in fresh samples. A significant correlation of frequencies was seen when
      comparing fresh with cryopreserved samples. Furthermore we recommend fresh human
      plasma used in UDS incubation media.

PMID- 10209336
TI  - The w/w+ SMART assay of Drosophila melanogaster detects the genotoxic effects of
      reactive oxygen species inducing compounds.
AB  - The somatic mutation and recombination w/w+ eye assay has been used for genotoxic
      evaluation of a broad number of chemicals with different action mechanisms
      yielding high values of sensitivity, specificity and accuracy. The aim of this
      work was to determine the utility of this assay in the evaluation of reactive
      oxygen species inducers. For this, we have tested eight compounds: diquat,
      paraquat, menadione, juglone, plumbagin, streptonigrin, tert-butyl hydroperoxide
      and 4-nitroquinoline 1-oxide, using the Drosophila Oregon K strain which had
      previously shown advantageous conditions to test this type of compounds. Diquat
      was the only chemical for which the results were clearly negative, probably
      because its high toxicity, whereas indications of a marginal genotoxicity raised
      for menadione. The remaining compounds were evaluated as positives. The
      conclusion of these experiments is that the w/w+ assay is capable to detect
      genotoxic effects induced by compounds that generate reactive oxygen species
      through different action mechanisms.

PMID- 10209337
TI  - Comparison of spontaneous and idoxuridine-induced micronuclei by chromosome
      painting.
AB  - Fluorescence in situ hybridisation (FISH) technique with chromosome specific
      library (CSL) DNA probes for all human chromosomes were used to study about 9000
      micronuclei (MN) in normal and idoxuridine (IUdR)-treated lymphocyte cultures of
      female and male donors. In addition, MN rates and structural chromosome
      aberrations were scored in Giemsa-stained chromosome spreads of these cultures.
      IUdR treatment (40 microg/ml) induced on the average a 12-fold increase of the MN
      rate. Metaphase analysis revealed no distinct increase of chromosome breaks but a
      preferential decondensation at chromosome 9q12 (28-79%) and to a lower extend at
      1q12 (8-21%). Application of FISH technique with CSL probes to one male and one
      female untreated proband showed that all human chromosomes except chromosome 12
      (and to a striking high frequency chromosomes 9, X and Y) occurred in spontaneous
      MN. In cultures containing IUdR, the chromosomal spectrum found in MN was reduced
      to 10 chromosomes in the male and 13 in the female proband. Eight chromosomes (2,
      6, 12, 13, 14, 15, 17 and 18) did not occur in MN of both probands. On the
      contrary chromosomes 1 and especially 9 were found much more frequently in the MN
      of IUdR-treated cultures than in MN of control cultures. DAPI-staining revealed
      heterochromatin signals in most of the IUdR-induced MN. In an additional study,
      spontaneous and IUdR-induced MN were investigated in lymphocytes of another
      female donor using CSL probes only for chromosomes 1, 6, 9, 15, 16 and X. The
      results confirmed the previous finding that chromosomes 1 and 9 occur very often
      in MN after IUdR-treatment. The results indicate that decondensation of
      heterochromatic regions on chromosomes 1 and 9 caused by IUdR treatment strongly
      correlates with MN formation by these chromosomes.

PMID- 10209338
TI  - Genotoxic evaluation of the antimicrobial drug, trimethoprim, in cultured human
      lymphocytes.
AB  - The antimicrobial drug, trimethoprim, was evaluated for genotoxicity in human
      peripheral blood lymphocyte cultures set-up from two healthy donors. Sister
      chromatid exchanges (SCE) and micronuclei (MN) were scored as genetic endpoints.
      The treatment was done using different trimethoprim concentrations ranging from 1
      to 100 microg/ml. From our results, we can conclude that this drug is able to
      induce both cytotoxic and moderate genotoxic effects, as revealed by the
      increases seen in SCE and MN frequencies in cultures from the two donors and, at
      least, at one of the concentrations tested.

PMID- 10209339
TI  - Low persistence of radiation-induced centromere positive and negative micronuclei
      in cultured human cells.
AB  - The micronucleus (MN) assay is widely used both in genetic toxicology and in the
      biomonitoring of human populations. Lymphocytes, cell lines, and bone marrow and
      epithelial cells are usually employed as target systems in such studies. However,
      little effort has been done to assess the persistence of MN in highly
      proliferative cells. To study the behaviour of MN containing whole chromosomes or
      acentric fragments, we have performed a time course experiment on the persistence
      of gamma-ray (3 Gy) induced MN in a human lymphoblastoid cell line. The frequency
      and content of MN were analyzed 1, 3, 7, 14, and 56 days after irradiation by
      pancentromeric fluorescence in situ hybridization (FISH). We observed a clear
      induction of both centromere positive and negative MN at completion of the first
      mitotic division. The frequency of both types of MN drastically declined to basal
      levels 7 days after irradiation with an identical kinetics. We therefore conclude
      that centromere positive and negative MN are highly unstable upon cell division,
      indicating that the MN assay could not be a good biomarker of DNA damage induced
      by acute treatments in highly proliferative cells. The implication of our
      findings in biomonitoring and in genotoxicity studies is discussed.

PMID- 10209340
TI  - Verapamil contributes to the clastogenic effects of acrylamide, cyclophosphamide,
      and dioxidine on somatic cells of BALB/C and C57BL/6 mice.
AB  - The chromosome aberration assay of metaphase bone marrow cells was used to study
      the clastogenic effects of acrylamide, cyclophosphamide, dioxidine, and their
      combinations with Verapamil (a calcium antagonist) in male BALB/C and C57BL/6
      mice. Verapamil gavage at single (5 mg/kg) and repeated doses (2.5 and 5 mg/kg
      five times at 24-h intervals) significantly enhanced the clastogenic activity of
      acrylamide (50 and 100 mg/kg intraperitoneally) in BALB/C mice; in C57BL/6 mice,
      this effect was only observed when they received Verapamil at doses of 2.5 mg/kg
      for 5 days. Verapamil administered repeatedly (2.5-10 mg, gavage) significantly
      increased the clastogenic activity of cyclophosphamide (10 mg/kg
      intraperitoneally) in C57BL/6 mice. In BALB/C mice, this effect of Verapamil was
      only observed at a dose of 10 mg/kg (gavage). When injected intraperitoneally at
      a single dose of 0.1-0.4 mg/kg, Verapamil significantly enhanced the clastogenic
      activity of cyclophosphamide in mice of both strains. This calcium antagonist
      produced identical effects when administered to BALB/C mice intraperitoneally
      (2.5 and 5 mg/kg) and by gavage (5 mg/kg) and to C57BL/6 mice intraperitoneally
      (5 and 10 mg/kg) and by gavage (2.5 mg/kg). Repeated administration of Verapamil
      (at all doses tested) promoted the clastogenic effect of dioxidine (100 mg/kg
      intraperitoneally) on C57BL/6 mice, having no such influence on BALB/C mice.
      These results demonstrate the co-clastogenic activity of Verapamil in mice and
      suggest that its specific manifestations depend on the dose, method, and route of
      drug administration and the genotype of test animals.

PMID- 10209341
TI  - An antitumor promoter from Moringa oleifera Lam.
AB  - In the course of studies on the isolation of bioactive compounds from Philippine
      plants, the seeds of Moringa oleifera Lam. were examined and from the ethanol
      extract were isolated the new O-ethyl-4-(alpha-L-rhamnosyloxy)benzyl carbamate
      (1) together with seven known compounds, 4(alpha-L-rhamnosyloxy)-benzyl
      isothiocyanate (2), niazimicin (3), niazirin (4), beta-sitosterol (5), glycerol-1
      (9-octadecanoate) (6), 3-O-(6'-O-oleoyl-beta-D-glucopyranosyl)-beta-sitosterol
      (7), and beta-sitosterol-3-O-beta-D-glucopyranoside (8). Four of the isolates (2,
      3, 7, and 8), which were obtained in relatively good yields, were tested for
      their potential antitumor promoting activity using an in vitro assay which tested
      their inhibitory effects on Epstein-Barr virus-early antigen (EBV-EA) activation
      in Raji cells induced by the tumor promoter, 12-O-tetradecanoyl-phorbol-13
      acetate (TPA). All the tested compounds showed inhibitory activity against EBV-EA
      activation, with compounds 2, 3 and 8 having shown very significant activities.
      Based on the in vitro results, niazimicin (3) was further subjected to in vivo
      test and found to have potent antitumor promoting activity in the two-stage
      carcinogenesis in mouse skin using 7,12-dimethylbenz(a)anthracene (DMBA) as
      initiator and TPA as tumor promoter. From these results, niazimicin (3) is
      proposed to be a potent chemo-preventive agent in chemical carcinogenesis.

PMID- 10209342
TI  - Effect of high-density extremely low frequency magnetic field on sister chromatid
      exchanges in mouse m5S cells.
AB  - The induction of sister chromatid exchanges (SCEs) was evaluated in the cultured
      mouse m5S cells after exposure to extremely low frequency magnetic field (ELFMF;
      5, 50 and 400 mT). Exposure to 5 mT and 50 mT ELFMF led to a very small increase
      in the frequency of SCEs, but no significant difference was observed between
      exposed and unexposed control cells. The cells exposed to 400 mT ELFMF exhibited
      a significant elevation of the SCE frequencies. There was no significant
      difference between data from treatments with mitomycin-C (MMC) alone and from
      combined treatments of MMC plus ELFMF (400 mT) at any MMC concentrations from 4
      to 40 nM. These results suggest that exposure to highest-density ELFMF of 400 mT
      may induce DNA damage, resulting in an elevation of the SCE frequencies. We
      suppose that there may be a threshold for the elevation of the SCE frequencies,
      that is at least over the magnetic density of 50 mT.

PMID- 10209343
TI  - Examination of various biomarkers measuring genotoxic endpoints from Barcelona
      airport personnel.
AB  - Three different biomarkers: sister-chromatid exchanges (SCE), micronuclei (MN),
      and the Comet assay, were used to evaluate different kinds of genetic damage in
      peripheral blood lymphocytes from 34 male workers at Barcelona airport, exposed
      to low levels of hydrocarbons and jet fuel derivatives. The control group
      consisted of 11 unexposed men. We also investigated the ras p21 protein levels in
      plasma, in order to evaluate whether the ras gene could serve as a suitable
      potential marker of carcinogenic pollution in occupationally exposed cohorts. SCE
      and MN analyses failed to detect any statistically significant increase in the
      airport workers when compared with the controls, and in fact, the frequency of
      binucleated cells with MN in the exposed group was significantly lower than that
      obtained in the control. However, slight but significant differences in the mean
      comet length and genetic damage index were observed between the exposed and
      control groups when using the Comet assay. There were no statistically
      significant differences between both groups in p21 plasma levels. Smoking was
      shown to affect significantly both SCE and high frequency cells (HFC) in the
      exposed group.

PMID- 10209344
TI  - Motor fluctuations in Parkinson's disease: pathophysiology and treatment.
AB  - At the initial stages of Parkinson's disease (PD), levodopa (LD) is able to
      reduce most motor symptoms and to significantly improve the patient's quality of
      life. However, in the vast majority of patients with prolonged LD usage, some
      decline in efficacy occurs and motor complications eventually begin to appear.
      These complications consist not only of daily fluctuations in the voluntary motor
      performance often accompanied by involuntary movements, but also of fluctuations
      in cognitive, autonomic, and sensory functions. Several recent studies on LD
      complications in PD have led to a better understanding of their pathophysiology
      and of the possible therapeutic interventions, and a summary of these findings is
      presented in this review. Different observations now suggest that postsynaptic
      pharmacodynamic factors play a major role in determining fluctuations in PD. Two
      explanations are given: chronic intermittent dopaminergic therapy may lead to
      postsynaptic receptor downregulation in PD; or, receptor changes in the striatum
      may occur independently of treatment as a result of structural adaptation of the
      postsynaptic dopaminergic system to the progressive decline of the nigrostriatal
      pathway. The hypothesis of reversible postsynaptic changes as the main mechanism
      underlying a fluctuating response to LD lends itself to a possible
      pharmacological manipulation of the dopaminergic response to reverse, or even
      avoid, motor fluctuations (initial monotherapy with dopamine agonists and early
      combination LD/dopamine agonists). The role of peripheral pharmacokinetics
      factors is also critical and the use of controlled release LD formulations, of
      monoamine oxidase (MAO)-B and of catechol-O-methyltransferase (COMT) inhibitors
      may all, to a different degree, improve such phenomena. In the last decade, there
      has been a resurgence in surgical therapies in advanced PD, due to higher levels
      of accuracy and safety provided by the new surgical devices, and to a more
      precise localization of the target areas allowed by the neurophysiological
      mapping techniques. The surgical procedures currently used in advanced PD are
      stereotactic brain lesions (internal globus pallidus and subthalamic nucleus),
      chronic brain stimulation (of the same nuclei) and striatal grafting of dopamine
      producing cells. All these procedures have already shown their efficacy in the
      management of severe fluctuations in PD, but their indications, and relative
      advantages and disadvantages, are still the subject of considerable debate and
      controversy.

PMID- 10209345
TI  - Influence of learning to read and write on the morphology of the corpus callosum.
AB  - Variations in the individual anatomy of the corpus callosum have been reported in
      several conditions. There seem to be genetic influencing factors, but it is
      impossible to rule out some environmental ones. This study focuses on the
      question of the environmental factors, using formal learning to read and write as
      the main difference in the groups to be compared. Based on magnetic resonance
      imaging sagital images, the contour of the corpus callosum (CC) of 41 carefully
      selected women (18 illiterate and 23 literate) was digitized. The comparison
      between the two groups showed a small difference in the region of the CC where
      parietal fibres are thought to cross. This region is thinner in illiterate
      subjects. As illiteracy in this group is the result of social constraints, and
      the two groups that were compared are well matched for other cultural and
      pragmatic aspects than literacy, the results are interpreted as showing the
      possible influence of formal learning to read and write, on the biological
      development of the brain.

PMID- 10209346
TI  - Cardiovascular autonomic function in patients with relapsing remitting multiple
      sclerosis: a new surrogate marker of disease evolution?
AB  - Twenty patients with active relapsing remitting multiple sclerosis (MS) were
      examined annually for 2 years with a set of autonomic function tests (AFT)
      consisting of heart rate variability during deep breathing (IE), standing-up, and
      ratios of Valsalva manoeuvre (VR). Disease characteristics, including T2-weighted
      magnetic resonance imaging (MRI) of the brain and the expanded disability status
      scale (EDSS) score were documented each year within 1 week of the AFT. The EDSS
      score, MRI load lesion and VR did not change significantly over the follow-up
      period. The IE and initial heart-rate on standing during the first 30 s
      (DeltaHRMAX) showed significant worsening during follow-up. No relationship was
      found between deterioration of AFT and EDSS score, number of exacerbations,
      duration of disease, gender, age, size and number of lesions on MRI. We conclude
      that patients with active relapsing remitting MS show progression of autonomic
      dysfunction over a relatively short time. Therefore, in the absence of changes in
      clinical disability or brain MRI lesion load, AFT might be useful as a sensitive
      surrogate outcome measure for demonstrating subclinical change in MS.

PMID- 10209347
TI  - Current status of multiple sclerosis therapy in Germany: a national survey.
AB  - We conducted a semi-standardized enquiry concerning diagnostic, immunotherapeutic
      and supportive care strategies for multiple sclerosis (MS). A questionnaire was
      sent to all German neurological departments in December 1996, with 63% (n = 244)
      responding before May 1997. As might be expected, MS therapy in Germany is not
      very standardized. Most clinics use intravenous steroids for treating relapses,
      although with different dosing regimens. Nevertheless, oral steroids are also
      used. Interferon-beta and azathioprine are both used for the treatment of
      relapsing-remitting MS at the same frequency. Only 33% of German neurological
      departments said that they used an immunomodulating agent for chronic-progressive
      cases, indicating it in about 50% of cases. Azathioprine is the drug of first
      choice, followed by methotrexate. Regarding supportive care measures, the
      technique of intermittent self-catheterization is widely under-represented.
      Despite the lack of conclusive evidence from prospective studies for the value of
      azathioprine, it is still one of the most commonly used drugs for the treatment
      of relapsing-remitting and chronic-progressive MS. There was no evidence of a
      consensus on treatment standards for chronic-progressive disease courses.

PMID- 10209348
TI  - Febrile convulsions in a Serbian region: a 10-year epidemiological study.
AB  - The first population-based study in the central region of the Republic of Serbia
      (total population 283,103) was carried out to assess some epidemiological
      features of febrile convulsions among children of between 6 months and 5 years of
      age. During the 10-year period, 1986 to 1995, there were 570 cases of the first
      febrile convulsions (287 males and 283 females). The average annual incidence
      rate was 3/1000 (2.9/1000 in males and 3.0/1000 in females), with the highest in
      1995. During the study period, a significantly increased linear regression trend
      was observed. During the follow-up period of 5 years for children who had their
      first febrile convulsions in 1989 and 1990 (total 154 cases), 27 (17.5%) had a
      recurrence of the disorder, and ten (6.5%) had one or more afebrile seizures, of
      whom seven children (4.5% of total sample) developed epilepsy (recurrent afebrile
      seizures).

PMID- 10209349
TI  - Sumatriptan nasal spray: a dose-ranging study in the acute treatment of migraine.
AB  - This multicentre, randomized, double-blind, placebo-controlled, parallel group
      dose-ranging study compared the efficacy and tolerability of four doses of
      sumatriptan nasal spray (2.5, 5, 10 and 20 mg) with a placebo, in the acute
      treatment of a single migraine attack. In total, 544 patients received the study
      medication as a single spray in one nostril, to treat a single migraine attack in
      the clinic. Efficacy assessments included the measurement of headache severity,
      clinical disability, and the presence/absence of associated symptoms. The
      incidence of headache recurrence was also assessed. The three highest doses of
      sumatriptan (5 mg 49%, 10 mg 46%, 20 mg 64%) were significantly better than the
      placebo (25%) at providing headache relief (moderate or severe headache improving
      to mild or none) 120 min after treatment (P </= 0. 01). Also, the 20 mg dose was
      significantly superior to both the 10 and 5 mg doses at this time point (P <
      0.05). The proportion of patients who were headache-free 120 min after treatment,
      was also higher following 20 mg (42%) rather than following any other sumatriptan
      dose (14-24%, P < 0.005 20 vs 10 mg) or placebo (11%). Headache recurrence in
      patients who had responded to initial treatment was reported by 30-41% of
      patients who received sumatriptan, compared with 33% of patients in the placebo
      group. Sumatriptan nasal spray was well tolerated, the incidence of adverse
      events with each dose of sumatriptan being similar to the placebo (20-27 and 23%,
      respectively). Apart from bad/bitter taste, the events were comparable with those
      reported following sumatriptan treatment by other routes of administration.

PMID- 10209350
TI  - Stroke following internal carotid artery occlusion - a contra-indication for
      intravenous thrombolysis?
AB  - Between March 1996 and December 1997, 15 consecutive patients with carotid artery
      occlusion diagnosed with duplex sonography were treated with intravenous
      recombinant tissue plasminogen activator (rt-PA), following a protocol similar to
      that of the National Institute of Neurological Disorders and Stroke (NINDS)
      study. On the basis of ultrasound findings, six of the 15 patients had internal
      carotid artery dissection (ICD), and the remaining nine had atherothrombotic
      internal carotid artery (ICA) occlusion. No relevant haemorrhagic complications
      were observed after rt-PA treatment of ICA occlusion. Excellent late functional
      outcome was observed in three of the 15 patients with ICA occlusion, moderate and
      poor outcome in four patients. Four patients died, and mortality was related to
      stroke severity upon admission. A good outcome seemed to be more likely in the
      small group of patients with ICD, than in the patients suffering atherothrombotic
      ICA occlusion. As the results of rt-PA treatment in this case series are by no
      means devastating, our data do not corroborate the hypothesis that patients with
      acute ischemic stroke following ICA occlusion should a priori be excluded from
      intravenous thrombolysis. The possible benefit of rt-PA treatment in stroke
      following acute or chronic ICA occlusion should be assessed in a larger
      prospective trial, for which this case series might serve as a pilot study.

PMID- 10209351
TI  - The effect of aspirin, ticlopidine and their low-dose combination on platelet
      aggregability in acute ischemic stroke: a short duration follow-up study.
AB  - We investigated the effects of aspirin (300 mg/d), ticlopidine (500 mg/d) and
      their low-dose combination (aspirin 100 mg/d plus ticlopidine 250 mg/d) on the
      platelet aggregability using the Wu and Hoak method. Each treatment group
      consisted of 25 patients with acute ischemic stroke. Platelet aggregation ratios
      (PAR) were measured on the 1(st) (before treatment), 10(th) and 90(th) days in
      the treatment groups and compared with those of 25 control cases. On the first
      day, comparison of PAR in each treatment group with the control was significant,
      while the differences between treatment groups were not significant. On the
      90(th) day, differences of PAR between aspirin and control were significant, but
      differences between the other treatment groups and the control group were not
      significant, indicating a lower anti-aggregant efficacy of aspirin. Our study
      suggests that PAR determination can be used to assess the efficacy of anti
      aggregant drugs. Our crude observation also suggests a higher anti-aggregant
      efficacy of ticlopidine, and aspirin plus ticlopidine, than aspirin. In addition,
      proper doses of aspirin plus ticlopidine may be a good choice for the prevention
      of ischemic stroke. Further studies are required to assess whether PAR
      determination could be useful for assessing patients at risk of stroke, and for
      drug selection for the prevention of stroke.

PMID- 10209352
TI  - Demonstration of delayed recovery from fatiguing exercise in chronic fatigue
      syndrome.
AB  - Patients with the chronic fatigue syndrome (CFS) complain consistently of delay
      in recovery of peripheral muscle function after exercise. The purpose of this
      study was to try to confirm this observation. A fatiguing exercise test was
      carried out on the quadriceps muscle group of ten patients and ten control
      subjects. The test consisted of 18 maximum voluntary contractions (MVCs) with a
      50% duty cycle (10 s contraction, 10 s rest), and the force generated by each
      contraction was recorded using a KinCom dynamometer. This was followed by a
      recovery phase lasting 200 min in which quadriceps strength was evaluated at
      increasing intervals, and a follow-up session at 24 h post-exercise involving
      three 10 s MVCs. Throughout the exercise period, the MVCs obtained from the
      control group were significantly higher than those of the patient group (P =
      0.006), but both groups showed a parallel decline in force over the 18
      contractions, in keeping with a similar endurance capacity. Recovery was
      prolonged in the patient group, however, with a significant difference compared
      to initial MVCs being evident during the recovery phase after exercise (P =
      0.001) and also at 24 h (P < 0.001). In contrast, the control group achieved MVCs
      which were not significantly different from initial values during the recovery
      phase, and maintained these at 24 h. These findings support the clinical
      complaint of delayed recovery after exercise in patients with CFS.

PMID- 10209353
TI  - Inter-laboratory validation of an ELISA for the determination of serum anti
      ganglioside antibodies.
AB  - Anti-ganglioside antibodies are frequently sought in the sera of patients with
      autoimmune peripheral neuropathy, using an enzyme-linked immunosorbent assay
      (ELISA) as the principal method for antibody detection. Wide variations in assay
      performance between laboratories have been reported. In this study, we
      established a standardized ELISA method between laboratories within the European
      Inflammatory Neuropathy Cause and Treatment (INCAT) group and determined the
      inter-laboratory variance in assay performance using both the standardized INCAT
      method and in-house local methods. As expected, the inter-laboratory variances
      were greater using local methods than using the standardized method, producing
      titre estimates which could be 24.8 or 7.6 times larger or smaller, respectively,
      than the true means for these laboratories. Using the standardized method, the
      within laboratory measurement error accounted for 41% of the inter-laboratory
      variation, providing a theoretical upper limit to which technical improvements
      within laboratories could reduce inter-laboratory variation. These data describe
      the intrinsic weaknesses within the widely used ganglioside antibody ELISA
      methods and reinforce the importance of inter-laboratory cooperation within this
      area. Standardized serological reagents used in this study are available from
      INCAT members.

PMID- 10209354
TI  - Functional and anatomical asymmetries of the human brain.

PMID- 10209355
TI  - Brucellar spinal epidural abscess.
AB  - Spinal epidural abscesses account for approximately one of every 10, 000
      admissions to tertiary hospitals. The midthoracic vertebrae are the most
      frequently affected, whilst the cervical spine is involved in fewer patients.
      Staphylococcus aureus is identified as the cause in most cases of epidural
      abscess; other bacteria responsible include Gram-negative bacteria, Streptococcus
      species and Brucella species. We report the case of a patient with cervical
      spondylodiscitis at level C4-C5 and an epidural abscess which was compressing the
      spinal cord and the retropharyngeal space. The previous symptoms of brucellosis
      were atypical. We discuss the clinical manifestations, diagnosis, treatment and
      prognosis of the case.

PMID- 10209356
TI  - Botulism: a case associated with pyramidal signs.
AB  - Botulism is a widespread neuroparalytic disease that may be confused with other
      neurological disorders. As it is potentially lethal, clinicians are required to
      be aware of its diagnosis and management. We report a case of botulism
      complicated by pyramidal signs in a 35-year-old woman. Clinical aspects,
      differential diagnoses and therapeutic problems are discussed.

PMID- 10209357
TI  - Reversible F-wave hyperexcitability associated with antibodies to potassium
      channels in Isaacs' syndrome.
AB  - We report a case of Isaacs' syndrome showing F-wave hyperexcitability which was
      reversible after either epidural block or plasmapheresis. A 14-year-old girl with
      progressive muscle cramp and myokymia in the legs showed high amplitude, long
      duration, polyphasic F-waves after either tibial nerve or peroneal nerve
      stimulation. Potassium current of PC-12 cell membrane was suppressed by her
      serum, IgM of which strongly reacted with proteins of approximately 50 kDa of the
      lysates of a PC-12 cell line. After an epidural nerve block with 1 per cent
      lidocaine 10 ml, the myokymia temporally improved, during which time the
      hyperexcitable F-waves became normalized. We treated her with double filtration
      plasmapheresis, which resulted in remarkable improvement of myokymia;
      simultaneously, the abnormal F-waves showed a decrease in amplitude, duration,
      and in the number of phases. We concluded that there was hyperexcitability of the
      proximal site of motor fibers in our patient, and possible immune mechanisms gave
      rise to the myokymia and unusual F-wave features.

PMID- 10209358
TI  - Circadian rhythm sleep disorder associated with pontine lesion.
AB  - A 55-year-old man presented with excessive daytime sleepiness and a circadian
      rhythm sleep disorder. Magnetic resonance imaging of the brain revealed a pontine
      lesion distinguishable from major cerebrovascular disease, demyelination and
      neoplasm. Benzodiazepines, antidepressants, methylcobalamine and thyroxine failed
      to synchronize the circadian rhythm. Antiepileptic drugs aggravated the
      condition, while melatonin and protireline partially relieved the patient from
      poorly controlled sleep disorder. A pontine lesion appeared to be related to the
      circadian rhythm sleep disorder of the patient.

PMID- 10209359
TI  - Atypical brachial plexopathy with pseudotumor cerebri.
AB  - A 24-year-old woman with previously known pseudotumor cerebri syndrome (PTCS)
      presented with severe pain in the neck and shoulders followed by the classical
      symptoms and signs of bilateral brachial neuritis. At the same time, there was a
      recurrence of the PTCS which had been in remission for more than one-and-a-half
      years. Despite treatment with high doses of methylprednisolone, intravenous
      immunoglobulins and repeated cerebrospinal fluid drainage, both brachial
      plexopathy and the PTCS continued to worsen. Both lumbosacral plexuses became
      involved and the visual acuity deteriorated to a level such that a
      lumboperitoneal shunt had to be inserted. The neurological condition started to
      improve progressively after 8 weeks. This case is, to our knowledge, the first
      where brachial plexopathy has been described in association with a PTCS. Although
      the pathogenesis of this association is not clear, there are enough data to
      suggest the existence of a continuum between extended brachial plexopathy and
      Guillain Barre syndrome, with which PTCS has been associated in some instances.

PMID- 10209360
TI  - Plus minus lid syndrome without ophthalmoplegia.

PMID- 10209362
TI  - Safe use of cricoid pressure.

PMID- 10209363
TI  - A survey of undergraduate teaching in anaesthesia.
AB  - Currently, no well accepted and clearly defined 'core' curriculum for
      undergraduate anaesthesia, teaching exists. To address this deficiency, we
      surveyed 73 university departments of anaesthesia and intensive care. Sixty-five
      replied from South-east Asia (12), Australasia (13), the UK and Ireland (28) and
      Canada (12). A questionnaire containing 37 items ranging from departmental
      structure to curriculum content was used. We found significant regional
      differences. Overall, most departments taught pharmacology of anaesthetic drugs
      (83%), pre-operative assessment (92%) and care of the unconscious patient (77%).
      Ninety-seven per cent taught airway management and intubation and 80% taught
      intravenous cannulation. Basic life support was taught by 92% and advanced life
      support by 71%. Fewer than half taught advanced trauma life support principles
      (44%). Critical care teaching was less well defined, but a consensus of schools
      taught respiratory failure and ventilation, management of circulatory shock and
      principles of sepsis and multi-organ system failure. Practical clinical skills
      were taught mainly using patients and simulators, 46% had a skills laboratory and
      six employed a resuscitation officer. However, it should be noted that we did not
      assess the quality and outcome of teaching.

PMID- 10209364
TI  - Hygienic practices of consultant anaesthetists: a survey in the north-west region
      of the UK.
AB  - Questionnaires were distributed to all 213 consultant anaesthetists in the North
      West region of the UK with a response rate of 68%. These questionnaires were
      designed to assess the hygienic precautions taken to reduce the potential for
      transmission of infectious agents to and from the patients under their care. Face
      masks and gloves were always used by 35.2% and 14.5%, respectively, while only
      36.4% washed their hands between cases. Most respondents have changed their
      practice since the recognition of HIV transmission (74.8%) and hepatitis B and C
      (69.8%). A high proportion of anaesthetists continue to administer anaesthesia
      despite suffering from respiratory (94%), gastrointestinal (42.9%) or herpes
      simplex (32.6%) infections. The anaesthetic breathing system was changed at the
      end of each day or following a high-risk case by 33.3% of the respondents, while
      just over 25% changed it following a known infected case. Bacterial filters were
      used by 17% and changed after each case by 7.2%. On a scale of 0-10 (10 =
      significant) anaesthetists rated their potential for transmitting or contributing
      to patient infection as a median of 3 (interquartile range: 2-6). The results of
      this study show that, although anaesthetists are well aware of proper hygienic
      practices, their performance falls short of accepted recommendations.

PMID- 10209365
TI  - Aspiration during anaesthesia: a review of 133 cases from the Australian
      Anaesthetic Incident Monitoring Study (AIMS).
AB  - Two-hundred and forty incidents of vomiting/regurgitation and aspiration were
      reported to the Anaesthetic Incident Monitoring Study database consisting of 5000
      reports. Of these, 133 cases of aspiration were recorded. Passive regurgitation
      occurred three times more commonly than active vomiting. Aspiration was reported
      twice as often in elective compared with emergency surgery, with 56% of incidents
      taking place during induction of anaesthesia. Anti-aspiration prophylaxis was
      prescribed in 14% of patients who subsequently aspirated; however, the majority
      of cases had at least one predisposing factor for regurgitation, vomiting or
      aspiration evident peri-operatively. While a major immediate physiological
      disturbance was common, long-term morbidity was not. Death ensued in five cases,
      all of whom had significant co-morbidities. Factors reported as contributing to
      the incident included error of judgement and fault of technique, while clinical
      experience and anaesthetic assistance tended to minimise the incident. Aspiration
      remains an important anaesthetic-related morbidity. The application of simple
      guidelines may have prevented the incident in 60% of all cases of aspiration.
      Ensuring airway security may be as important as chemoprophylaxis in its
      prevention.

PMID- 10209366
TI  - Analgesic and adverse effects of a low dose of intrathecally administered
      hyperbaric neostigmine alone or combined with morphine in patients submitted to
      spinal anaesthesia: pilot studies.
AB  - We report the analgesic and adverse effects of intrathecally administered
      hyperbaric neostigmine, alone or combined with morphine, in two patients
      suffering from severe lower limb ischaemic pain (group 1), five patients
      undergoing Caesarean section (group 2) and 19 patients scheduled for orthopaedic
      surgery (group 3) under spinal anaesthesia. These patients were enrolled in three
      pilot studies undertaken before the initiation of the planned controlled studies.
      Hyperbaric neostigmine (50 micrograms in glucose 8%) produced analgesia lasting
      more than 6 h in patients of group 1, but the effect was accompanied by episodes
      of vomiting. A lower dose of hyperbaric neostigmine (25 micrograms), alone (two
      patients) or combined with morphine (50 micrograms) (one patient) produced no
      discernible analgesic effect but was followed by severe nausea and vomiting
      within 15 min of intrathecal injection in patients of group 2. Two patients who
      received hyperbaric morphine (100 micrograms) had analgesia for more than 24 h
      and exhibited mild pruritus. In patients of group 3, hyperbaric neostigmine alone
      (25 micrograms) produced analgesia of shorter duration than neostigmine (25
      micrograms) plus morphine (50 micrograms) or morphine (100 micrograms).
      Neostigmine alone or combined with morphine was associated with adverse events,
      mainly nausea and vomiting that lasted up to 9-12 in some patients. Other adverse
      events observed included anxiety, somnolence and involuntary defaecation. Most
      patients who received the combination of neostigmine and morphine exhibited more
      severe nausea, vomiting and somnolence. The low clinical efficacy of
      intrathecally administered neostigmine alone or in combination with morphine
      impairs the design of a double-blind protocol and might restrict the clinical
      usefulness of the drug combination.

PMID- 10209367
TI  - Choice of cuff inflation medium during nitrous oxide anaesthesia.
AB  - Air, saline and a mixture of nitrous oxide and oxygen were used to inflate the
      cuffs of tracheal tubes inserted into three groups of patients, during nitrous
      oxide anaesthesia. Large increases in intracuff pressure were seen in the air
      group, but no morbidity resulted. The intracuff pressure decreased in the gas mix
      group and leaks occurred in some patients. Initial adjustment of cuff pressure
      was more difficult in the saline group but the pressure remained stable
      thereafter.

PMID- 10209368
TI  - Extent and practicalities of filter use in anaesthetic breathing circuits and
      attitudes towards their use: a postal survey of UK hospitals.
AB  - A postal survey of 120 UK hospitals was conducted to assess the current use of
      filters in anaesthetic breathing systems and consultant anaesthetists' opinion of
      their value; 76% of the questionnaires were returned complete. The survey showed
      that 77.2% of anaesthetic departments use a new filter for every case, a variety
      of different filter types being used. A connector distal to the filter was used
      in 78.3% of patients, providing a possible route for cross infection.
      Anaesthetists rated the prevention of bacterial infection and gross contamination
      as being higher priorities than the prevention of viral infection. Of those
      surveyed, 66.3% believed filters were worthwhile whereas only 35.9% thought they
      were cost effective. Only 34.8% of anaesthetists believed that the supposed extra
      efficiency of pleated hydrophobic membrane filters over electrostatic filters
      merited their extra cost.

PMID- 10209369
TI  - The physiological and pharmacological roles of cytochrome P450 isoenzymes.
AB  - The cytochrome P450 isoenzymes are a superfamily of haemoprotein enzymes that
      catalyse the metabolism of a large number of endogenous and exogenous compounds.
      Recently, the cytochrome isoenzymes have been shown to be important in the
      synthesis of steroid hormones and bile acids, the arachidonic acid cascade and in
      central nervous function. These enzymes are a major determinant of the
      pharmacokinetic behaviour of numerous drugs. Furthermore, alterations in
      cytochrome P450 activity have been implicated in some diseases.

PMID- 10209370
TI  - Safe pre-operative fasting times after milk or clear fluid in children. A
      preliminary study using real-time ultrasound.
AB  - Gastric emptying of orange-flavoured glucose (group I), low-fat milk (group II)
      and breast milk (group III) was evaluated in 45 ASA grade I children of < or = 5
      years of age by using real-time ultrasonography and residual gastric volume and
      pH was then measured. In 15 more children, residual gastric volume and pH was
      measured after a midnight fast (group IV). Mean (SD) gastric emptying time in
      group I was 1.53 (0.25) h (range 1.00-1.75), group II 2.32 (0.31) h (range 1.75
      2.75) and group III 2.43 (0.27) h (range 2.00-2.75). According to Robert and
      Shirley's criteria, no children of group I and II were found to be 'at risk' at 2
      h and 3 h, respectively, but 13.3% of group III children were labelled as 'at
      risk' at 3 h. The incidence of 'at risk' children in group IV was 33.3%. It was
      concluded that 3% fat milk or 17.5% glucose in a volume of 10 ml.kg-1 (maximum
      volume of 100 ml) can be given in children safely 3 h and 2 h, respectively,
      before anaesthesia. More real-time studies are required on breast milk to
      establish guidelines for its potential use as a pre-operative feed 3 h before
      anaesthesia.

PMID- 10209371
TI  - Cricoid pressure: knowledge and performance amongst anaesthetic assistants.
AB  - We investigated the cricoid pressure technique of 135 anaesthetic assistants
      attending the annual conference of the British Association of Operating
      Department Assistants in May 1997. Their knowledge and training were assessed
      using a structured interview. Technique was assessed using a simulator measuring
      applied force during sham cricoid pressure. Our additional aims were to see
      whether a knowledge of the required force and practical training in the
      application of a target force would affect performance. Our results highlight a
      lack of knowledge relating to the manoeuvre. Only about one-third of subjects
      could quote an appropriate force and fewer than half could give a single
      contraindication to its use. Very few subjects had been trained on a model before
      practising the technique on a patient. Technique was poor and we observed a large
      variation in the force actually applied. Performance, as assessed by the
      variability of forces applied and proportion of subjects applying force within
      our target range (30-44 N), was improved markedly by providing simple instruction
      about the required force in an understandable form. Performance was further
      improved by practical training in the application of target force on a simulator.

PMID- 10209372
TI  - Propofol auto-co-induction as an alternative to midazolam co-induction for
      ambulatory surgery.
AB  - We propose the use of an intravenous propofol/propofol auto-co-induction
      technique as an alternative to propofol/midazolam for induction of anaesthesia.
      We have studied 54 unpremedicated ASA 1 or 2 patients undergoing day-stay
      anaesthesia for minor orthopaedic surgery. All received 10 micrograms.kg-1 or
      alfentanil before induction, followed by either midazolam 0.05 mg.kg-1, propofol
      0.4 mg.kg-1 or saline, and 2 min later, a propofol infusion at a rate of 50 mg.kg
      1.h-1 until loss of eyelash reflex. We compared pre- and postinduction
      haemodynamic changes, complications at insertion of a laryngeal mask airway and
      recovery from anaesthesia in the three groups. Both co-induction techniques
      showed less postinduction hypotension and significant reduction of the total
      induction dose of propofol when compared to the control group. In the
      propofol/propofol group there was a decreased incidence of apnoea during
      induction of anaesthesia. These patients were discharged from hospital 2 h after
      the end of anaesthesia whereas patients in the midazolam/propofol group were
      discharged after 2 1/2 h (p < 0.001).

PMID- 10209373
TI  - Peribulbar anaesthesia: a double-blind comparison of three local anaesthetic
      solutions.
AB  - A prospective, randomised, double-blinded study comparing three agents for
      peribulbar anaesthesia is reported. Sixty patients undergoing extracapsular
      cataract extraction under local anaesthesia were randomly allocated to receive
      peribulbar anaesthesia with lignocaine 2% with adrenaline; prilocaine 3% with
      felypressin 0.03 IU.ml-1 or 2% lignocaine and 0.5% bupivacaine in a ratio of 1:1,
      using a standardised two-injection technique. The pain of injection, time of
      onset of the block and the operating conditions at the start and finish of
      surgery were assessed. Peribulbar anaesthesia using lignocaine 2% was
      significantly more painful than the other solutions. The onset of anaesthesia
      adequate for surgery was similar in all three groups. Prilocaine 3% with
      felypressin was associated with the greatest number of blocks providing total
      akinesia of the eye. Inadequate duration of anaesthesia was seen in only one
      case; the solution used for this block was 2% lignocaine.

PMID- 10209374
TI  - Anaesthesia for daycase gynaecological laparoscopy: a survey of clinical practice
      in the United Kingdom.
AB  - Gynaecological laparoscopy is a daycase procedure that can be associated with
      significant morbidity and patients may require admission to hospital for
      overnight stay. Following a decision to administer intraperitoneal bupivacaine
      routinely to such patients in our day surgery unit, we wished to establish
      whether this was routine practice elsewhere. We therefore carried out a postal
      survey of consultant anaesthetists in the UK who regularly anaesthetise patients
      undergoing daycase gynaecological laparoscopy, addressing a number of clinical
      issues. The results of the survey are presented, discussed and compared with
      published advice.

PMID- 10209375
TI  - The effect of intravenous tenoxicam on pruritus in patients receiving epidural
      fentanyl.
AB  - In this prospective randomised study, pruritus and pain were evaluated in
      patients undergoing abdominal surgery during which epidural fentanyl was
      administered. All patients had an epidural catheter inserted at the time of
      surgery. Epidural fentanyl 100 micrograms was administered intra-operatively and
      infused at a concentration of 2 micrograms.ml-1 for 48 h postoperatively. All
      patients received a standard anaesthetic and, in addition, the study group had a
      20 mg bolus of tenoxicam intravenously, intra-operatively. Patients receiving
      tenoxicam demonstrated significantly lower pruritus and pain scores at 30 min, 2,
      4, 8 and 24 h postoperatively as well as reduced pethidine requirements for
      breakthrough pain in the first 24 h. In conclusion, tenoxicam 20 mg significantly
      reduces the incidence and severity of postoperative pruritus in patients who
      received peri-operative epidural fentanyl. In addition, it significantly reduces
      pain and further analgesic requirements postoperatively.

PMID- 10209376
TI  - Diagnosing brain death: the importance of documenting clinical test results.
AB  - Eighty-three cases of brain stem death referred to the South Thames Transplant Co
      ordination Service were audited to determine the quality of brain stem death test
      records. Documentation of brain stem death tests were complete in only 41 (44%)
      cases at the time of referral. There was no significant difference in
      completeness, whether documentation was in patient's notes or on a designated
      checklist (p = 0.14). There were a greater number of omissions when the tests
      were documented in patient's notes rather than on a form (p = 0.01). There is a
      necessity to improve the quality of brain stem death test documentation in order
      to facilitate organ donation and safeguard the integrity of brain stem death
      testing. This requires a commitment by clinicians to improve the quality of
      documentation, which can be accomplished by recording all aspects of brain stem
      death tests, including the conclusion on a single designated checklist.

PMID- 10209377
TI  - Regional anaesthesia--before or after general anaesthesia?

PMID- 10209378
TI  - Regional anaesthesia--before or after general anaesthesia?

PMID- 10209380
TI  - Tracheal aerosol administration of bronchodilators in ventilated patients.

PMID- 10209379
TI  - Epidural haematoma following anticoagulant treatment in a patient with an
      indwelling epidural catheter.

PMID- 10209381
TI  - Tracheal aerosol administration of bronchodilators in ventilated patients.

PMID- 10209383
TI  - Breathing system filters.

PMID- 10209382
TI  - Checklist for anaesthesia machines.

PMID- 10209384
TI  - Anaesthetic machine alarm use.

PMID- 10209386
TI  - Sharp or blunt tipped needles for retrobulbar anaesthesia.

PMID- 10209385
TI  - Parental anxiety before elective surgery in children.

PMID- 10209387
TI  - Preparation of local anaesthetic solutions for peribular blocks.

PMID- 10209388
TI  - Gastro-oesophageal reflux during day-case gynaecological laparoscopy.

PMID- 10209389
TI  - Life-threatening complications of hiatus hernia.

PMID- 10209390
TI  - Morbidity and economic considerations of spinal anaesthesia in the elderly.

PMID- 10209391
TI  - The use of sumatriptan in the treatment of postdural puncture headache after
      accidental lumbar puncture complicated a blood patch procedure.

PMID- 10209392
TI  - Anaesthesia and fluorosis.

PMID- 10209393
TI  - Failure of the Univent bronchial blocker in sealing the bronchus.

PMID- 10209394
TI  - Forced-air warming blanket and surgical access.

PMID- 10209395
TI  - Oesophageal Doppler interference during abdominal ultrasound examination.

PMID- 10209396
TI  - Evaluation of a new epidural fixation device.

PMID- 10209397
TI  - Things are not as they seem.

PMID- 10209398
TI  - Things are not as they seem.

PMID- 10209399
TI  - Things are not as they seem.

PMID- 10209400
TI  - Overcoming the beard.

PMID- 10209401
TI  - Overcoming the beard.

PMID- 10209402
TI  - Unexpected benefits of anaesthesia.

PMID- 10209403
TI  - Transcranial Doppler: preventing stroke during carotid endarterectomy.
AB  - Carotid endarterectomy (CEA) is more effective at preventing strokes than medical
      therapy alone in those patients with severe symptomatic stenosis of the internal
      carotid artery and this benefit persists despite a perioperative stroke/death
      rate of approximately 5%. Thromboembolism has been established as the underlying
      cause of the majority of perioperative strokes, but this could not be detected
      using the existing methods of monitoring or quality control. Early studies
      demonstrated that transcranial Doppler monitoring (TCD) could detect
      intraoperative embolism, but the clinical significance of this finding was
      questioned as the incidence of these emboli far exceeded the incidence of
      perioperative strokes. This study aimed to establish the clinical relevance of
      TCD-detected emboli during CEA by differentiating emboli into two broad
      categories; air and particulate, and comparing the quantity of each with a
      variety of clinical outcomes including neurological and cognitive function,
      retinal fundoscopy, automated visual fields and CT/MRI brain scans. This
      prospective study was performed on 100 consecutive patients undergoing CEA with
      all assessments performed pre- and postoperatively by independent specialists in
      the relevant fields. Embolisation was detected in 92% of successfully monitored
      operations. Most emboli were characteristic of air microbubbles and not
      associated with the development of adverse clinical events. However, emboli
      characteristic of particulate material were detected during the initial
      dissection phase and in the recovery phase after final restoration of flow. These
      particulate emboli were associated with the development of both neurological and
      cognitive deficits. In particular, persistent embolisation after final
      restoration of flow heralded incipient carotid artery thrombosis and the
      development of stroke. Early intervention based on the TCD evidence of continuing
      embolisation can prevent the stroke from occurring.

PMID- 10209405
TI  - Palliation of dysphagia from inoperable oesophageal carcinoma using Atkinson
      tubes or self-expanding metal stents.
AB  - Until recently, intubation for the palliation of malignant dysphagia has relied
      upon the insertion of a variety of plastic tubes. Self-expanding metal stents are
      reported to have a lower complication rate. We have compared the results of
      Atkinson tube insertion with self-expanding metal stents in patients with
      inoperable oesophageal carcinoma. From 1990 to 1994 Atkinson tubes were inserted
      for the palliation of dysphagia from oesophageal cancer, from 1994 onwards self
      expanding metal stents were used. Complications, mortality and hospital stay were
      compared in both groups of patients. In all, 87 patients with inoperable
      oesophageal carcinoma were treated, 46 with an Atkinson tube and 41 with metal
      stents. Complications occurred at similar rates in both groups (56% Atkinson
      tubes, 44% metal stents). There was a significantly higher perforation rate
      associated with Atkinson tube insertion (8 patients, 17%) compared with metal
      stents (1 patient, 2.4%, P = 0.02, chi 2). The length of stay was also
      significantly higher in the Atkinson tube group (median 10 days) compared with
      the metal stent group (3 days, P < 0.01, Mann-Whitney U test). Mortality rates
      were similar in both groups. The use of metal stents for the palliation of
      dysphagia in inoperable oesophageal carcinoma results in a lower perforation rate
      and a reduced length of stay and they represent a significant advantage over
      Atkinson tubes.

PMID- 10209406
TI  - An instrument to facilitate open laparoscopy.

PMID- 10209404
TI  - Duplex scanning may be used selectively in patients with primary varicose veins.
AB  - Reflux was assessed using hand-held Doppler (HHD) and duplex scanning in 72
      patients with primary, previously untreated varicose veins (108 limbs). The aims
      of the study were (i) to compare the accuracy of HHD assessment with duplex
      scanning, (ii) to assess the benefit of tourniquet testing and (iii) to identify
      patients who would benefit from a policy of selective duplex scanning. HHD
      accurately assesses the saphenofemoral junction (SFJ) and long saphenous vein
      (LSV) reflux. HHD assessment of the saphenopopliteal junction (SPJ) reflux has a
      low positive predictive value. A high negative predictive value reflects absent
      SPJ reflux assessed using HHD accurately. Tourniquet testing is not helpful.
      Selective duplex scanning of limbs with suspected SPJ reflux, no identifiable
      site of reflux or posterior thigh perforator reflux on HDD (39% of limbs), would
      result in the appropriate surgical procedure being performed in 102 (94%) limbs,
      excessive surgery in 5 (5%) limbs and inadequate surgery in only 1 (1%) limb. The
      use of selective criteria for duplex scanning would reduce the workload of the
      vascular laboratory without compromising patient care.

PMID- 10209407
TI  - Laparoscopic staging of gastric cancer is safe and affects treatment strategy.
AB  - The accuracy of laparoscopic staging has been documented, but its safety and
      impact on clinical decision making are less clear. In a prospective series of 64
      patients referred to a single consultant, laparoscopy was performed in 49, after
      exclusion of patients unlikely to derive benefit from laparoscopic staging. The
      prelaparoscopy treatment plan was altered in 17 (34%). Laparoscopy detected 11
      cases of peritoneal and four cases of liver metastasis, of which nine and two,
      respectively, were not detected by CT scan. Laparoscopy was useful in assessing
      fitness for major surgery, the planned extent of which was reduced in five cases
      as a result. Port site metastasis occurred in one case of stage IVB cancer, in
      conjunction with widespread progressive disease. Laparoscopic staging is
      recommended in gastric cancer, since it causes important changes to the
      management plan in one-third of cases, and the risks of port site metastasis
      appear low.

PMID- 10209408
TI  - Case report. Reoperative laparoscopic biliary surgery.

PMID- 10209409
TI  - Psoas abscesses complicating colonic disease: imaging and therapy.
AB  - Most surgeons think of psoas abscesses as a very rare condition related to
      tuberculosis of the spine, but in contemporary surgical practice they are more
      usually a complication of gastrointestinal disease. A case note study was
      undertaken on all patients treated for psoas abscess at two large hospitals in
      the mid-Trent region over a 2-year period. All seven patients presented with
      pyrexia, psoas spasm, a tender mass and leucocytosis. The diagnosis was made on
      abdominal radiographs in one patient, CT scan in three, MRI in two, and
      ultrasound in one. Aetiological factors included Crohn's disease in three,
      appendicitis in two, and sigmoid diverticulitis and metastatic colorectal
      carcinoma in one each. Six patients underwent transabdominal resection of the
      diseased bowel, retroperitoneal debridement and external drainage of the abscess
      cavity. Percutaneous drainage was performed in one. Two patients had more than
      one surgical exploration for complications. There were no deaths and the hospital
      stay ranged from 8-152 days. Psoas abscess can be a difficult and protracted
      problem. Bowel resection, thorough debridement, external drainage and concomitant
      antibiotics are essential for psoas abscesses complicating gastrointestinal
      disease. Defunctioning stomas may be necessary. However, in some cases a
      multidisciplinary approach may be required, as psoas abscesses can involve bone
      and joints.

PMID- 10209410
TI  - Labial fat pad grafts (modified Martius graft) in complex perianal fistulas.
AB  - Complex perianal fistulas may at times be very difficult to treat. New
      vascularised tissue can reach the perineum from leg muscles and the omentum. A
      less well-known source is the labial fat tissue (modified Martius graft) which
      has a robust posterolateral pedicle and which can be useful as an adjunctive
      technique for high anterior anal and rectovaginal fistulas. Between November 1993
      and July 1997, eight women (age range 18-55 years) underwent modified Martius
      grafting, six of the eight having a rectovaginal fistula and two a high complex
      (suprasphincteric) perianal fistula. Anorectal advancement flaps were performed
      in five patients and three had a transperineal approach with simultaneous
      anterior sphincter repair because of concurrent anal incontinence. All patients
      had a defunctioning stoma. The fistula healed in six of the eight patients (75%)
      and recurred in two patients. The stoma has been closed in five of the eight
      patients (one patient's fistula has healed but her stoma cannot be closed because
      of anal incontinence). This is a useful technique when confronted with a
      difficult anterior fistula in women.

PMID- 10209411
TI  - Case report. Recovery of shoulder movement in patients with complete axillary
      nerve palsy.
AB  - Classical anatomical teaching suggests that the deltoid muscle is the main
      abductor of the shoulder. We present three cases of proven complete paralysis of
      the deltoid with an almost full range of movement of the shoulder owing to the
      compensatory action of accessory muscles. The mechanisms by which this occurs are
      described.

PMID- 10209412
TI  - Case report. Bilateral simultaneous patellar tendon ruptures associated with
      osteogenesis imperfecta.

PMID- 10209413
TI  - Case report. Post-traumatic tibial recurvatum: resolution with growth.
AB  - The outcome of proximal tibial fractures in children is often complicated by the
      development of malalignment. Progressive valgus deformity is frequently seen, but
      is known to correct spontaneously in a high proportion of cases; however,
      recurvatum of the tibia usually requires surgical intervention. We present a
      child with a proximal tibial metaphyseal fracture who developed increasing tibial
      recurvatum which corrected spontaneously.

PMID- 10209414
TI  - Surgical history. The history and evolution of surgical instruments. IX Scissors
      and related pivot-controlled cutting instruments.

PMID- 10209416
TI  - Surgical technique. Securing of surgical drains in the neck.

PMID- 10209415
TI  - Ultrasound-guided unilateral neck exploration for sporadic primary
      hyperparathyroidism: is it worthwhile?
AB  - The role of preoperative localisation tests before initial neck exploration for
      primary hyperparathyroidism (PHP) remains controversial, as does the optimal
      surgical approach. We report our experience with preoperative ultrasound (US) and
      the operative management of sporadic PHP between 1990 and 1995. Preoperative US
      was carried out by an experienced radiologist. Three surgeons adopted a policy of
      'selective' US-guided unilateral neck exploration (UNE); the fourth surgeon
      performed routine bilateral neck exploration (BNE). There were 72 patients: 26
      men and 46 women, with a mean age of 57.4 +/- 12.5 years (range 21-80 years). All
      patients underwent initial neck exploration for 'sporadic' PHP, of whom 63 had
      preoperative US. This was positive in 52 patients; 27 of whom underwent a UNE, 23
      had a BNE, and two patients had a UNE converted to a BNE. Patients with
      'negative' US (n = 11), and those receiving no preoperative localisation test (n
      = 90) underwent a BNE. The sensitivity, specificity and accuracy of US were 80%
      (52/65), 100% (61/61), and 90% (113/126), respectively. Comparable success rates
      were achieved (BNE: 97% (33/34) vs UNE: 93% (27/29), P < 0.05), with very low
      morbidity. Failures with the scan-guided UNE were caused by missed contralateral
      adenomas. An experienced radiologist and a low incidence of multiglandular
      disease (MGD) are essential prerequisites for the scan-guided unilateral
      approach. An experienced surgeon, on the other hand, is the only prerequisite for
      the 'gold standard' bilateral approach.

PMID- 10209417
TI  - Glove usage and reporting of needlestick injuries by junior hospital medical
      staff.
AB  - The use of gloves when conducting invasive procedures and the reporting of
      needlestick injuries have been strongly encouraged. Despite this, neither
      practice appears to be universal. In order to determine the rates of glove usage
      and needlestick injury reporting, we conducted a survey of junior doctors in
      three hospitals in the UK. Of the 190 respondents, the majority rarely wore
      gloves for venesection, insertion of intravenous cannulas or arterial blood gas
      sampling. For more major procedures (insertion of central venous lines, insertion
      of thoracostomy tubes, suturing) gloves were invariably worn. Only 17.5% of
      needlestick injuries were reported. The rates of glove usage and needlestick
      injury reporting were lower than previous studies have demonstrated in North
      America. Surgeons suffered the most needlestick injuries and were the least
      likely to report them. The low reporting rate may have serious implications,
      particularly in view of the new Government guidelines on needlestick injuries
      which involve HIV-infected blood. By failing to use gloves and report needlestick
      injuries, junior doctors, in particular surgeons, are placing themselves and
      patients at increased risk of blood-borne transmissible diseases.

PMID- 10209418
TI  - Laparoscopic cholecystectomy, bile duct injury and the British and Irish surgeon.

PMID- 10209419
TI  - An audit of outcome including patient satisfaction with immediate breast
      reconstruction performed by breast surgeons.

PMID- 10209420
TI  - Which treatment would patients prefer for their varicose veins.

PMID- 10209421
TI  - Causes of late diagnosis in cases of colorectal cancer seen in a district general
      hospital over a 2-year period.

PMID- 10209422
TI  - An ileal enterotomy for colonic lavage and primary anastomosis in left colon
      obstruction also used to defunction anastomosis.

PMID- 10209423
TI  - "New" surgical treatments for glaucoma.

PMID- 10209424
TI  - Progress in diabetic maculopathy.

PMID- 10209425
TI  - Ophthalmic medical assistants.

PMID- 10209426
TI  - Deep sclerectomy with collagen implant: medium term results.
AB  - AIMS: To study prospectively the success rate and complications of deep
      sclerectomy with collagen implant (DSCI), a new non-penetrating filtration
      procedure. METHODS: Non-randomised prospective trial involving consecutive
      patients. 100 eyes of 100 patients with medically uncontrolled primary and
      secondary open angle glaucoma. A superficial scleral flap was raised and a deep
      sclerectomy was performed in the scleral bed. Schlemm's canal was opened and
      dissection of the cornea was performed up to Descemet's membrane, at which point
      aqueous percolated through the remaining trabeculo-Descemet's membrane. A
      collagen implant was sutured radially in the scleral bed. Visual acuity,
      intraocular pressure (IOP) measurements, and slit lamp examinations were
      performed before surgery and after surgery at 1 and 7 days, and 1, 3, 6, 9, 12,
      18, 24, 30, and 36 months. RESULTS: The mean follow up period was 17.8 (SD 8.7)
      months. The mean preoperative IOP was 27.8 (8.6) mm Hg; the mean postoperative
      IOP was 5.7 (4.0) at day 1, 11.2 (4.6) at month 1, 14.0 (3.5) at month 12, and
      13.0 (3.8) at month 36. Complete success rate, defined as an IOP lower than 21 mm
      Hg without medication, was 44.6% at 36 months. Qualified success rate, defined as
      an IOP lower than 21 mm Hg with medication, was 97.7% at 36 months. Early
      postoperative complications included hyphaema in seven patients, would leak in 10
      patients, and subtle choroidal detachment in 11 patients. Goniopuncture was
      performed in 41 of the patients, and 5-fluorouracil injections were made in 23
      patients; cataract progression occurred in seven patients. When comparing the
      different types of open angle glaucoma, no difference was found in terms of
      reduction in IOP, number of patients requiring antiglaucoma medications, or
      success rate. CONCLUSIONS: Deep sclerectomy with collagen implant appears to
      provide reasonable control of IOP at medium term follow up, with few immediate
      postoperative complications.

PMID- 10209427
TI  - Vitrectomy for cystoid macular oedema with attached posterior hyaloid membrane in
      patients with diabetes.
AB  - AIM: To report the success of vitrectomy in eliminating cystoid macular oedema
      and improving vision in three eyes of two patients with diabetic cystoid macular
      oedema. In all of the eyes there was no ophthalmoscopic evidence of traction from
      a posterior hyaloid membrane or from proliferative tissue. METHODS: Pars plana
      vitrectomy was performed on three eyes of two patients with diabetic cystoid
      macular oedema who did not show traction upon examination with a slit lamp
      biomicroscope and a scanning laser ophthalmoscope. RESULTS: Cystoid changes
      disappeared 1, 3, and 5 days, postoperatively, and diffuse macular oedema
      resolved within 2 weeks. The visual acuity was improved and maintained.
      CONCLUSION: Vitrectomy can be effective in some patients with diabetic cystoid
      macular oedema even in patients who lack evidence of traction by ophthalmoscopy.

PMID- 10209429
TI  - Retrospective analysis of risk factors for late presentation of chronic glaucoma.
AB  - BACKGROUND: Why some individuals present to the ophthalmologist in the early
      stages of chronic glaucoma but others present with very advanced visual field
      loss is a question which has received little attention. This study is an attempt
      to identify some basic characteristics of people who present with late glaucoma.
      METHODS: A retrospective case-control study by medical record review was
      employed. 100 cases and 100 controls were identified from the notes of patients
      presenting to Moorfields Eye Hospital glaucoma service between July 1993 and July
      1995. Cases were defined as new patients presenting with absolute field loss
      within five degrees of fixation and a cup to disc ratio of greater than 0.8 in
      one or both eyes. Controls were new patients with no absolute field loss within
      20 degrees in either eye, but otherwise typical glaucomatous field loss and a cup
      to disc ratio of greater than 0.5 or a difference of 0.2 or more between the
      discs. RESULTS: The ethnic origin, sex, referral source, presenting IOP, and age
      of the subjects studied were independently associated with late presentation. An
      African Caribbean patient is estimated to be four and a half times more likely to
      attend with advanced field loss than a white patient of similar age, sex, IOP,
      and referral source (adj OR: 4.55, 95% CI [1.57, 13.18]). A female patient is
      estimated to be one third (0.34, [0.15, 0.74]) as likely to attend late than a
      male patient of the similar age, IOP, ethnic origin, and referral source. A
      patient referred via any source other than an optometrist with the correct
      diagnosis is estimated to be greater than four times (4.32 [1.89, 9.88]) more
      likely to be a late attender than a patient of the same sex, ethnicity, and
      similar age but referred with a diagnosis of glaucoma. There was a trend of
      increasing odds of late presentation with increasing age (adj OR per 10 years,
      baseline 40-49 years 1.68 [1.22, 2.20]). A patient whose presenting IOP is 21-25
      mm Hg is estimated to be a quarter (0.24, [0.09, 0.64]) as likely to attend with
      advanced field loss than a patient of the same ethnic origin, sex, age, referral
      source, but with presenting IOP of greater than 31 mm Hg. CONCLUSIONS: These data
      strongly suggest that certain subgroups of patients with glaucoma are likely to
      be at greater risk of presenting with advanced and irremediable field loss.

PMID- 10209428
TI  - Mid-peripheral pattern electrical retinal responses in normals, glaucoma
      suspects, and glaucoma patients.
AB  - AIMS: Reliance on intraocular pressure, optic nerve cupping changes, nerve fibre
      layer integrity, and visual field changes may delay treatment of glaucoma since
      irreversible changes may have already occurred at the time of diagnosis. Abnormal
      pattern electrical retinal responses (PERR or PERG) have been demonstrated in
      patients with ocular hypertension (no visual field changes) and glaucoma when
      visual stimulation was presented to the central field. Since glaucomatous visual
      field changes tend to occur first in the mid-periphery, the use of PERR outside
      of the central field may offer an earlier indication of glaucomatous involvement.
      METHODS: Glaucoma suspects and glaucoma patients were derived from a university
      practice. Normal subjects were recruited from non-patient volunteers. Alternating
      bar gratings were presented in the supranasal, supratemporal, infratemporal, and
      infranasal visual field. Six spatial frequencies, from 0.25 to 6.0 cycles per
      degree, were used for normal volunteers; three spatial frequencies, from 0.38 to
      1.5 cycles per degree, were presented to suspects and glaucoma patients. Time of
      onset of the first negative (N35) and first positive peak (P50) and the amplitude
      consisting of the absolute difference between the first negative peak and first
      positive peak (P50 amplitude) are reported. Age corrected values were determined
      for normals, suspects, and glaucoma patients for each spatial frequency and for
      each quadrant in the visual field. RESULTS: Mean P50 amplitudes from normal
      subjects showed spatial tuning in all quadrants with reduced low frequency
      attenuation. Normals demonstrated a small decline in amplitude with age. Glaucoma
      patients demonstrated an age corrected reduction in amplitude and early implicit
      times. Glaucoma suspects had values between those of normal and glaucoma
      subjects. P50 amplitudes were weakly correlated with increasing cup to disc
      diameter ratio. A glaucoma patient with asymmetric visual field loss demonstrated
      significant diminution of the PERR bilaterally. CONCLUSION: The PERR, using mid
      peripheral stimulation, may be a sensitive tool for the early detection of
      glaucoma. Further refinements can speed clinical data acquisition and enhance
      signal to noise ratio.

PMID- 10209430
TI  - Immediate intraocular pressure response to selective laser trabeculoplasty.
AB  - BACKGROUND/AIMS: Selective laser trabeculoplasty targets the pigmented trabecular
      meshwork cells without damage to the trabecular meshwork architecture in vitro. A
      study was conducted in vivo of eight eyes with uncontrolled open angle glaucoma
      to ascertain the immediate intraocular response to selective laser
      trabeculoplasty. METHODS: The trabecular meshwork of each eye was treated 360
      degrees with a frequency doubled Q-switched Nd:YAG laser. Intraocular pressure
      was measured 1, 2, 24 hours and 1, 4, 6 weeks after treatment. RESULTS: The
      average preoperative intraocular pressure was 26.6 (SD 7) mm Hg (range 18-37).
      Two hours and 6 weeks respectively after selective trabeculoplasty intraocular
      pressure was reduced in all the eyes treated with an average fall of 10.6 (5.2)
      mm Hg or 39.9%. A pressure spike of 10 mm Hg verified in one eye 1 hour after
      treatment. CONCLUSIONS: Selective laser trabeculoplasty decreased intraocular
      pressure by an amount similar to that achieved with standard trabeculoplasty.
      Additional study is needed to determine whether the beneficial effect is
      sustained over a longer period of follow up.

PMID- 10209431
TI  - Effect of acute intraocular pressure changes on short posterior ciliary artery
      haemodynamics.
AB  - BACKGROUND/AIMS: Vascular insufficiency due to abnormal autoregulation has been
      proposed as a major factor in the development of glaucoma. The anterior optic
      nerve is primarily perfused by the short posterior ciliary arteries. The
      autoregulatory capacity of these vessels in response to acutely elevated
      intraocular pressure (IOP) was examined in normal human subjects. METHODS: Colour
      Doppler imaging was performed on the short posterior ciliary arteries of 10
      normal subjects at baseline and during four incremental IOP elevations. Using a
      scleral suction cup placed temporally, IOP was elevated to approximately 25, 30,
      40, and 50 mm Hg. Additional measurements were performed immediately after
      pressure release. Systolic and diastolic flow velocities were measured and
      Pourcelot's resistivity index was calculated. RESULTS: Systolic and diastolic
      flow velocities decreased linearly with each incremental increase in IOP (p <
      0.001). Pourcelot's resistivity index increased linearly with each incremental
      increase in IOP (p < 0.001). Changes in end diastolic velocity, peak systolic
      velocity, and Pourcelot's resistivity index were linearly related to changes in
      IOP. CONCLUSION: The normal healthy eye is not able to autoregulate to maintain
      PCA blood flow velocities in response to acute large elevations in IOP.

PMID- 10209432
TI  - High incidence of glucose intolerance in Vogt-Koyanagi-Harada disease.
AB  - AIMS: To evaluate glucose tolerance of patients with Vogt-Koyanagi-Harada (VKH)
      disease before systemic corticosteroid therapy, and to assess changes brought on
      by treatment. METHODS: 20 VKH patients with acute bilateral panuveitis were
      studied. 20 healthy adults and 11 Behcet's disease patients with active
      uveoretinitis served as controls. A 75 g oral glucose tolerance test (OGTT) was
      given in the acute stage of ocular inflammation before systemic corticosteroid
      therapy. The OGTT was repeated in the convalescent stage of VKH disease in the
      patients with glucose intolerance before treatment. Insulin response was examined
      at the same time as the OGTT when possible. RESULTS: 55% of VKH patients (11/20)
      showed glucose intolerance but no apparent insulin secretion deficiency was
      detected. Four of seven patients in the convalescent stage showed improvement of
      glucose tolerance. None of the normal controls or disease controls showed glucose
      intolerance. CONCLUSION: A high incidence of glucose intolerance was found in the
      acute stage of VKH disease. However, glucose intolerance improved in most cases
      after systemic corticosteroid therapy. It is possible that glucose intolerance
      seen in VKH patients may be related to the autoimmune inflammatory process of
      this disease.

PMID- 10209433
TI  - Preretinopic changes in the colour vision of juvenile diabetics.
AB  - AIMS: To examine the colour vision of juvenile patients suffering from diabetes
      mellitus without retinopathy in relation to metabolic and ophthalmic state.
      METHODS: Metameric matches, both Rayleigh (red/green) and Moreland (blue/green)
      were used to test the colour vision yearly of 10 juvenile patients. The patients
      were monitored over 4 years, and during the final year, their blood glucose level
      was determined directly after testing colour vision. An ophthalmic examination
      was performed on the day of colour vision testing and blood and urine were
      analysed regularly throughout the 4 years. Their results are compared with an
      aged matched control group of 20 subjects, seven of whom were retested after 9-16
      months. RESULTS: After 4 years, the colour vision results show an enlarged
      matching range for the Moreland match, as well as a smaller increase in the
      matching range for the Rayleigh match. No significant correlation was found
      between blood glucose at the time of testing and any of the variables measured.
      CONCLUSION: The pattern of colour vision deficits in metameric matching shown by
      juvenile diabetics is consistent with postreceptoral alterations of the inner
      retina, at this preretinopic stage of disease. Duration of diabetes is correlated
      with both colour vision changes and morphological alteration of the retina.

PMID- 10209434
TI  - Cystoid macular oedema and cytomegalovirus retinitis in patients with HIV disease
      treated with highly active antiretroviral therapy.
AB  - BACKGROUND: Although cystoid macular oedema (CMO) is a rare cause of visual loss
      in AIDS related cytomegalovirus (CMV) retinitis, nine cases are reported of CMO
      occurring in HIV infected patients with a prior diagnosis of CMV who were
      receiving highly active antiretroviral therapy (HAART). METHODS: Medical and
      ophthalmological records of nine AIDS patients with inactive CMV retinitis were
      retrospectively analysed. Ophthalmic examination data, laboratory findings, and
      the systemic antiviral treatment were studied. Ophthalmic examination included
      visual acuity, anterior chamber flare measured with the laser flare cell meter
      (LCFM), vitreous haze quantification according to the Nussenblatt grading system,
      and fluorescein angiography. RESULTS: Nine HIV infected patients, eight men and
      one woman, mean age 39 years (range 29-53 years) presented with inactive CMV
      retinitis and CMO. On fluorescein angiography, CMO was present only in eyes (14
      eyes) with signs of previous CMV retinitis. CMV retinitis was inactive in all of
      them. Visual acuity ranged from 20/200 to 20/30. In 10 eyes with CMV retinitis,
      anterior chamber flare measured with the LCFM ranged from 18.5 to 82 photons/ms
      (mean 35.42 ph/ms). A significant vitreous inflammation (1.5+) was observed in
      eight eyes. All patients had been treated with anti-CMV drugs for a mean period
      of 18 months (range 12-36 months). All nine patients received HAART with a
      combination of two nucleotide analogue reverse transcriptase inhibitors and one
      protease inhibitor for a mean period of 14 months (range 9-18 months). The HIV
      viral load was below detectable levels (< 200 copies/ml) in eight patients and
      low (3215 copies/ml) in one. At the time of CMO, the median CD4+ lymphocyte count
      was 232 cells x 10(6)/l (range 99-639). CONCLUSION: In AIDS patients, the usual
      absence of intraocular inflammation in eyes affected by CMV retinitis has been
      tentatively explained by the profound cellular immunodeficiency. In these
      patients, treated with HAART, CD4+ counts were increased for several months (mean
      14 months). In their eyes, CMV retinitis was associated with significant ocular
      inflammation and CMO. These findings could be related to the restoration of
      immune competence after HAART as recently shown.

PMID- 10209436
TI  - Quantitative assessment of macular thickness in normal subjects and patients with
      diabetic retinopathy by scanning retinal thickness analyser.
AB  - AIMS: To evaluate the scanning retinal thickness analyser (RTA), a novel non
      invasive imaging instrument, in diagnosing and quantitatively characterising
      diabetic macular oedema, and to investigate the relation between central macula
      thickness measured by RTA and other clinical examinations. METHODS: Central
      macular thickness was measured using the RTA in 40 normal subjects and 60
      patients with diabetic retinopathy. The reproducibility of the retinal thickness
      measurements was evaluated by calculating the mean of the inter- and intrasession
      variations. Central macular thickness was correlated with the results of visual
      acuity measurements, biomicroscopy, and fluorescein angiography. RESULTS: Intra-
      and intersession reproducibility of the RTA in normal subjects was plus or minus
      5.2% (16 microns) and plus or minus 6.1% (19 microns), respectively. The mean
      central macular thickness was 182 (SD 16) microns in normal subjects, 283 (116)
      microns in diabetic eyes without clinically significant macular oedema (CSMO),
      and 564 (168) microns in diabetic eyes with CSMO. Central macular thickness was
      significantly greater (p < 0.001) in eyes with diabetic retinopathy than in
      normal subjects, even when macular thickening did not meet the standard for CSMO
      (p = 0.019) measured by biomicroscopy. Although greater fluorescein leakage at
      the macula results in greater central macular thickness, only eyes with diffuse
      leakage had statistically significant macular thickening compared with normal
      subjects (p = 0.022). Central macular thickness measured with the RTA was
      significantly correlated with the logarithmic converted visual acuity (r2 = 0.76)
      in diabetic eyes. CONCLUSION: Scanning RTA, which has good reproducibility, might
      be useful to quantitatively detect and monitor macular thickening in diabetic
      retinopathy. Central macular thickness was highly correlated with logarithmic
      converted visual acuity in diabetic macular oedema.

PMID- 10209435
TI  - Arterial blood flow characteristics in central retinal vein occlusion and effects
      of panretinal photocoagulation treatment: an investigation by colour Doppler
      imaging.
AB  - AIMS: To determine whether an increase in vascular resistance in the central
      retinal and ophthalmic arterial circulations contributes to the development of
      central retinal vein occlusion (CRVO), or haemodynamic alterations in central
      retinal and ophthalmic arteries occur secondary to the vein occlusion as
      increased intravascular pressure is transferred through the capillary bed to the
      arterial side and the effect of panretinal photocoagulation treatment on these
      circulations in ischaemic cases. METHODS: The ophthalmic and central retinal
      arteries of the affected and non-affected eyes of 20 patients with non-ischaemic
      CRVO, 13 patients with ischaemic CRVO, and 22 control subjects were investigated
      by colour Doppler imaging. Panretinal photocoagulation (PRP) treatment was
      applied to the eyes with ischaemic CRVO. Maximum and minimum blood flow
      velocities, and resistivity indexes were calculated in the affected and healthy
      eyes of patients and in the control eyes. RESULTS: Average blood flow velocity in
      the central retinal and ophthalmic arteries of patients with non-ischaemic CRVO
      did not differ from their fellow eyes, but a significantly lower average blood
      flow velocity was found in the ophthalmic and central retinal arteries of the
      patients with ischaemic CRVO compared with their fellow eyes. Patients with
      ischaemic CRVO had significantly lower blood flow velocities in their ophthalmic
      and central retinal arteries than non-ischaemic cases that were further reduced
      following PRP treatment. CONCLUSION: This study suggests that impaired arterial
      blood flow observed in patients with CRVO may be partly related to secondary
      changes in the retrobulbar arterial circulation as a result of enhanced arterial
      resistance following CRVO. These data also demonstrate that PRP treatment
      decreases retinal and ophthalmic blood flow velocities in patients with ischaemic
      CRVO.

PMID- 10209437
TI  - The need for cataract surgery: projections based on lens opacity, visual acuity,
      and personal concern.
AB  - AIM: To assess the projected needs for cataract surgery by lens opacity, visual
      acuity, and patient concern. METHODS: Data were collected as part of the
      Melbourne Visual Impairment Project, a population based study of age related eye
      disease in a representative sample of Melbourne residents aged 40 and over.
      Participants were recruited by a household census and invited to attend a local
      screening centre. At the study sites, the following data were collected:
      presenting and best corrected visual acuity, visual fields, intraocular pressure,
      satisfaction with current vision, personal health history and habits, and a
      standardised eye examination and photography of the lens and fundus. Lens
      photographs were graded twice and adjudicated to document lens opacities.
      Cataract was defined as nuclear greater than or equal to standard 2, 4/16 or
      greater cortical opacity, or any posterior subcapsular opacities. RESULTS: 3271
      (83% response) people living in their own homes were examined. The participants
      ranged in age from 40 to 98 years and 1511 (46.2%) were men. Previous cataract
      surgery had been performed in 107 (3.4%) of the participants. The overall
      prevalence of any type of cataract that had not been surgically corrected was
      18%. If the presence of cataract as defined was considered the sole criterion for
      cataract surgery with no reference to visual acuity, there would be 309 cataract
      operations per 1000 people aged 40 and over (96 eyes of people who were not
      satisfied with their vision, 210 eyes of people who were satisfied with their
      vision, and three previous cataract operations). At a visual acuity criterion of
      less than 6/12 (the vision required to legally drive a car), 48 cataract
      operations per 1000 would occur and people would be twice as likely to report
      dissatisfaction with their vision. CONCLUSIONS: Estimates of the need for
      cataract surgery vary dramatically by level of lens opacity, visual acuity, and
      patient concern. These data should be useful for the planning of health services.

PMID- 10209438
TI  - Measuring the effectiveness of cataract surgery: the reliability and validity of
      a visual function outcomes instrument.
AB  - AIMS: To assess test-retest reliability and validity of the "TyPE" patient self
      assessed visual function questionnaire, as part of a study in two hospitals
      measuring the effectiveness of cataract surgery. The American TyPE questionnaire
      had minor adaptations made for use in Britain. METHODS: Test-retest reliability
      was assessed on 63 out of 378 adult cataract surgery patients in the study, using
      Spearman correlation coefficients and kappa coefficients of agreement.
      "Construct" validity was evaluated by comparing the association between changes
      in visual function questionnaire scores after surgery, with patients' perception
      of change in visual function obtained by independent interview of 24 patients.
      RESULTS: The TyPE questionnaire items showed very good test-retest reliability.
      Average Spearman and kappa coefficients for 39 patients from hospital 1 were 0.93
      and 0.84 respectively. Spearman and kappa coefficients of 0.9 and 0.81 were
      obtained for those nine patients in hospital 2 where both the test and retest
      questionnaires were filled in by the same people. However, for the 15 patients
      from hospital 2, where the questionnaire was filled in by different people in the
      retest, reliability was less good: the Spearman coefficients were still high,
      average 0.72, but the kappa coefficients were poor, 0.27. Good construct validity
      was exhibited, with a correlation of 0.79 between change in distance vision score
      from the questionnaires and the independent interview. CONCLUSIONS: The adapted
      TyPE questionnaire is both very reliable and has good construct validity. The
      kappa coefficient should be used wherever possible to evaluate reliability. The
      test-retest reliability and validity and practicability of other visual function
      questionnaires have not been assessed adequately, and further development should
      be carried out of all such questionnaires, so that they may be introduced into
      routine clinical care.

PMID- 10209439
TI  - Results of small incision extracapsular cataract surgery using the anterior
      chamber maintainer without viscoelastic.
AB  - AIMS: To assess the efficacy of extracapsular cataract surgery using the anterior
      chamber maintainer (ACM) without the use of viscoelastic. To compare the effects
      of this surgical technique on non-diabetic and diabetic patients. METHODS: A
      prospective single armed clinical trial of 46 eyes in 46 patients undergoing
      cataract surgery using the ACM without viscoelastic. Patients were assessed
      preoperatively and at 3 weeks, 3 months, and 12 months postoperatively. The main
      outcome variables included visual acuity, surgically induced astigmatic change
      (SIAC), changes in endothelial cell density (ECD), and morphology affecting the
      central and superior regions of the cornea. RESULTS: Postoperatively, 56% and 70%
      of patients had unaided visual acuities of 6/12 or better at 3 weeks and 3 months
      respectively. Even after excluding those patients with pre-existing maculopathy
      (including diabetic maculopathy), there remains a significant difference between
      the non-diabetic and diabetic groups in terms of the proportion of patients
      attaining an unaided visual acuity of 6/12 or better at both 3 weeks (p = 0.003)
      and 3 months (p = 0.001). Three months postoperatively, the SIAC based upon the
      keratometric and refractive data was 1.1 dioptres (D) and 1.3 D respectively.
      There was no statistically significant difference in the SIAC when the non
      diabetic and diabetic groups were compared. The mean central and superior
      endothelial cell losses at 3 months postoperatively were 16% and 22% respectively
      and at 12 months postoperatively were 20% and 25% respectively. The diabetic
      group demonstrated greater endothelial cell losses and a more marked and
      protracted deviation of endothelial cell morphology from normality when compared
      with the non-diabetic group; however, the differences did not reach statistical
      significance. CONCLUSIONS: The efficacy of small incision cataract surgery using
      the ACM in terms of visual outcome and induced astigmatism is comparable with the
      results obtained using other techniques that utilise a similar size of incision.
      However, in view of the magnitude and range of the endothelial cell losses
      associated with this technique the concurrent use of viscoelastic is suggested.
      There does not appear to be a statistically or clinically significant difference
      between non-diabetic and diabetic patients in terms of the magnitude of the
      endothelial cell losses or in the wound healing response in the 12 months after
      cataract surgery using the ACM.

PMID- 10209440
TI  - Orbital lymphangioma: an analysis of 26 patients.
AB  - AIM: To evaluate retrospective data on the clinical findings, histological
      features, radiological diagnosis, and management outcomes in orbital
      lymphangioma. METHODS: Data on 26 orbital lymphangioma patients managed over 16
      years were re-evaluated. The computed tomograph and magnetic resonance scans and
      histological slides were reviewed. Parametric techniques were used to assess
      correlations among clinical, radiological, and histopathological factors.
      RESULTS: At presentation proptosis was present in 85%, ptosis in 73%, and
      restrictive eye movements in 46% of patients. The accuracy of the initial
      radiology interpretations was 77%. 24 cases required one or more surgeries. The
      mean follow up was 9.2 years (range 1-14 years). 58% of patients developed
      recurrences. In cases that recurred, motility restriction was significantly more
      frequent at initial examination than cases without recurrence (p < 0.05). After
      therapy, 75% of patients were satisfied with their visual function and cosmetic
      appearance. CONCLUSIONS: Conservative management of orbital lymphangioma with
      multiple partial resections may achieve satisfactory results.

PMID- 10209441
TI  - A single technique to correct various degrees of upper lid retraction in patients
      with Graves' orbitopathy.
AB  - BACKGROUND: Several lengthening techniques have been proposed for upper eyelid
      retraction in patients with Graves' orbitopathy and variable rates of success
      have been reported. Most authors recommend different procedures for different
      degrees of retraction, but cannot prevent residual temporal retraction in a
      significant number of cases. The modified levator aponeurosis recession described
      by Harvey and colleagues, in which the lateral horn is cut completely, seems to
      be an exception to this rule, but was evaluated in a limited number of cases
      only. METHOD: The authors further modified Harvey's technique by dissecting the
      aponeurosis together with Muller's muscle of the tarsus and the conjunctiva
      medially only to the extent necessary to achieve an acceptable position and
      contour of the eyelid in upright position. They also used an Ethilon 6.0 suture,
      instead of Vicryl, on a loop. It is placed between the tarsal plate and the
      detached aponeurosis to prevent spontaneous disinsertion. This modification was
      used in 50 Graves' patients (78 eyelids) with a upper lid margin-limbus distance
      ranging from 1 to 7 mm and evaluated using strict criteria. RESULTS: A perfect or
      acceptable result was obtained in 23 of 28 patients (82%) with bilateral
      retraction and in 18 of 22 patients (82%) with unilateral retraction. Seven
      eyelids were overcorrected (too low) and three undercorrected, necessitating
      reoperation. All other eyelids had an almond-like contour and a lid crease of 10
      mm or less. No complications except subcutaneous haematomas were seen. Two
      patients showed a recurrence of lid retraction 9 months after the operation.
      CONCLUSION: This technique is safe and efficacious and can be used for all
      degrees of eyelid retraction.

PMID- 10209442
TI  - Long-term results after surgical basal cell carcinoma excision in the eyelid
      region.
AB  - AIMS: To evaluate the data for patients with basal cell carcinoma (BCC) in the
      eyelid region, to demonstrate histologically controlled tumour excision, and to
      prove the efficacy of the treatment on the basis of long term observations.
      METHODS: Retrospective analysis of 382 microscopically controlled BCC excisions
      in the eyelid apparatus (350 patients) in a follow up study over 5.7 (SD 1.1)
      years. Tumour location, tumour size, and histological results were recorded. The
      same procedure was followed for recurrences. Follow up examinations were carried
      out 1, 3, 6, and 12 months after the operation, and then annually for a further 4
      years or longer. RESULTS: A recurrence rate of 5.36% was observed after the
      primary operation. 60.3% of first recurrences occurred in the medial canthus,
      41.2% showed in depth extension, and sclerosing types were overly represented at
      35.3%. After the second operation the recurrence rate increased to 14.7% and
      reached 50% after a third and fourth operation. CONCLUSIONS: The greatest risk of
      recurrence exists for BCCs of the medial canthus with in depth extension, and for
      sclerosing types. The recurrence rate increases after every operation. For high
      risk cases, consideration should be given to adjuvant treatment such as
      radiotherapy.

PMID- 10209443
TI  - Diseases associated with ocular surface abnormalities: the importance of reflex
      tearing.
AB  - AIM: To investigate the correlation between tear function tests and ocular
      surface integrity in patients with dry eye. METHODS: 297 dry eye patients (55
      Sjogren's syndrome, two male and 53 female, average age 52.4 (SD 15.0) years, and
      242 non-Sjogren's syndrome, 41 male and 201 female, average age 53.5 (14.1)
      years) were examined. The following tear function tests were performed: (1)
      cotton thread test, (2) Schirmer test with topical anaesthesia, (3) Schirmer test
      without anaesthesia, (4) Schirmer test with nasal stimulation, (5) tear clearance
      test, and (6) tear break up time (BUT). The ocular surface was evaluated by rose
      bengal and fluorescein staining. Correlation analysis was performed between each
      tear function index and vital staining scores. RESULTS: Among the six tear
      function tests, the Schirmer test with nasal stimulation correlated most with
      both of the vital stains (rho = 0.530 for rose bengal and 0.393 for fluorescein).
      The Schirmer test with or without anaesthesia correlated slightly with rose
      bengal staining, whereas tear clearance test and tear break up time slightly
      correlated with fluorescein staining. CONCLUSION: Vital staining of the ocular
      surface correlates most with reflex tearing measured by the Schirmer test with
      nasal stimulation.

PMID- 10209444
TI  - Reflective meniscometry: a non-invasive method to measure tear meniscus
      curvature.
AB  - AIMS: To devise a method to measure tear meniscus curvature by a non-invasive
      specular technique. METHODS: A photographic system was devised. The system
      consisted of a camera and an illuminated target with a series of black and white
      stripes oriented parallel to the axis of the lower tear meniscus. The target was
      mounted on a flash gun close to the objective of a Brown macrocamera and
      calibrated using a graduated series of glass capillaries of known diameter,
      ground down to expose the inner wall. It was then applied to normal human eyes (n
      = 45) to measure the tear meniscus curvature. A video system was also assessed
      which provided qualitative online information about the tear meniscus. RESULTS:
      Using the photographic system, measured values for capillary radii were in
      excellent agreement with theoretical calculations (r2 = 0.996, p < 0.0001). The
      radii of curvature of lower tear menisci in normal human subjects (mean 0.365 (SD
      0.153) mm, range 0.128-0.736; n = 45) were similar to those reported in the
      literature. Both systems demonstrated variations in meniscus shape. The video
      system provided stable images of human menisci over prolonged periods of time and
      promises to be useful for the analysis of dynamic changes in meniscus volume.
      CONCLUSIONS: Reflective meniscometry is a non-invasive technique providing
      quantitative information about tear meniscus shape and volume and of potential
      value in the study of ocular surface disease.

PMID- 10209445
TI  - Intraepithelial and invasive squamous cell carcinoma of the conjunctiva: analysis
      of 60 cases.
AB  - AIM: To evaluate the clinical features, treatment results, and recurrence rates
      in patients with either intraepithelial or invasive squamous cell carcinoma of
      the conjunctiva. METHODS: Retrospective analysis of 60 cases (22 conjunctival
      intraepithelial and 38 invasive squamous cell carcinomas) to determine patterns
      of clinical presentation, aetiological factors, and treatment results. The mean
      patient age was 64 years old. 70% of the patients were male. Patients were
      treated with a variety of therapies, depending on the degree of tumour
      involvement; most cases were treated with frozen section controlled excision and
      adjunctive cryotherapy. Modified eye wall resection or enucleation was done for
      intraocular invasion and exenteration was done for orbital involvement. RESULTS:
      Red eye (68%) and ocular irritation (57%) were the most common presenting
      symptoms. 44% of the patients had other eye findings consistent with extensive
      solar exposure. 20% of the patients had a history of malignant skin tumours.
      Visceral malignancies developed in 8%. Scleral involvement was present in 14
      (37%), intraocular involvement in five (13%), and orbital invasion in four (11%)
      cases with invasive squamous cell carcinoma. After a mean follow up of 56 months
      (18-226 months) the rate of new or recurrent tumours was 4.5% for intraepithelial
      squamous carcinoma and 5.3% for invasive squamous cell carcinoma. No patient
      developed metastases or tumour related deaths. CONCLUSION: Excision with
      intraoperative control of the surgical margins and adjunctive cryotherapy results
      in good tumour control rates.

PMID- 10209446
TI  - Peribulbar anaesthesia during keratoplasty: a prospective study of 100 cases.
AB  - AIMS: A prospective study was carried out in order to evaluate the efficacy and
      safety of peribulbar anaesthesia during keratoplasty and to describe surgical
      conditions. METHODS: Of 137 consecutive keratoplasties, 100 (73%) were performed
      under peribulbar anaesthesia. Patients received a mean volume of 16.5 (SD 4) ml
      (range 9-22 ml) of a mixture of etidocaine, bupivacaine, and hyaluronidase.
      Ocular compression duration was at least 20 minutes and intraocular pressure
      (IOP) was measured with a Tonopen after injection, compression, and before
      trephination. Degree of akinesia, pain scoring, complications, and surgical
      conditions were studied. RESULTS: Before trephination, IOP was 5.73 mm Hg below
      the preinjection value and was never above 21 mm Hg. Akinesia was complete in 80%
      of cases and 94% of patients found that surgery was painless. Two patients (2%)
      were very agitated during surgery. The last patient presented with an acute
      intraoperative suprachoroidal haemorrhage that did not result in a true expulsive
      haemorrhage despite an "open sky" situation. Surgical conditions were judged to
      be optimal by the patients in 92% of cases and by the surgeon in 98% of cases.
      CONCLUSION: These results demonstrate that peribulbar anaesthesia offers
      excellent anaesthesia and akinesia during keratoplasty and may be recommended for
      this type of surgery.

PMID- 10209447
TI  - c-myc, p53, and Bcl-2 expression and clinical outcome in uveal melanoma.
AB  - AIMS: Overexpression of c-myc protein has independent prognostic significance in
      a variety of primary and metastatic cutaneous melanomas which suggests a possible
      role for this gene in melanomagenesis. We have therefore examined the importance
      of this oncogene in uveal melanoma and studied the coexpression of two other gene
      products, Bcl-2 and p53, which might contribute to its effect. METHODS: The
      percentage of cells positive for nuclear c-myc expression was estimated by flow
      cytometric analysis of nuclei extracted from paraffin blocks. The expression of
      Bcl-2 and p53 protein was assessed by immunohistochemistry. A total of 71 tumours
      were studied and the results compared with survival with a mean follow up period
      of 6 years. RESULTS: c-myc was expressed in > 50% of the cells by 70% of the
      tumours, and was independently associated with improved survival in a Cox
      multiple regression-model. Although Bcl-2 was expressed by the majority of the
      cells in 67% tumours, it was without effect on prognosis. None of the cases
      studied showed convincing positivity for p53. Analysis of coexpression showed
      that the best survival was seen in c-myc+/Bcl-2+ tumours and the worst in c-myc
      /Bcl-2-tumours. CONCLUSION: The finding of improved rather than reduced survival
      in c-myc positive tumours is at variance with skin melanoma. There was no
      evidence to suggest that c-myc was modulated by upregulation of Bcl-2 or p53
      inactivation/mutation. Although Bcl-2 is unlikely to have any effect on tumour
      growth or metastasis, it could contribute to the general lack of susceptibility
      to apoptosis in these tumours.

PMID- 10209448
TI  - Homozygosity mapping and linkage analysis demonstrate that autosomal recessive
      congenital hereditary endothelial dystrophy (CHED) and autosomal dominant CHED
      are genetically distinct.
AB  - BACKGROUND: Congenital hereditary endothelial dystrophy (CHED) is a corneal
      dystrophy characterised by diffuse bilateral corneal clouding resulting in
      impaired vision. It is inherited in either an autosomal dominant (AD) or
      autosomal recessive (AR) manner. The AD form of CHED has been mapped to the
      pericentromeric region of chromosome 20. Another endothelial dystrophy, posterior
      polymorphous dystrophy (PPM), has been linked to a larger but overlapping region
      on chromosome 20. A large, Irish, consanguineous family with AR CHED was
      investigated to determine if there was linkage to this region. METHODS: The
      technique of linkage analysis with polymorphic microsatellite markers amplified
      by polymerase chain reaction (PCR) was used. In addition, a DNA pooling approach
      to homozygosity mapping was employed to demonstrate the efficiency of this
      method. RESULTS: Conventional genetic analysis in addition to a pooled DNA
      strategy excludes linkage of AR CHED to the AD CHED and larger PPMD loci.
      CONCLUSION: This demonstrates that AR CHED is genetically distinct from AD CHED
      and PPMD.

PMID- 10209450
TI  - Vogt-Koyanagi-Harada disease masquerading anterior ischaemic optic neuropathy.

PMID- 10209449
TI  - Management of inherited outer retinal dystrophies: present and future.

PMID- 10209451
TI  - Acute retinal necrosis after neonatal herpes encephalitis.

PMID- 10209452
TI  - Retinoschisis associated with disc coloboma.

PMID- 10209453
TI  - Corneal endothelial changes and trinucleotide repeat expansion of DRPLA gene.

PMID- 10209454
TI  - Myopia in diethylstilboestrol exposed amblyopic subjects.

PMID- 10209455
TI  - Cataract and season of birth.

PMID- 10209456
TI  - Osteon-odonto-keratoprosthesis surgery.

PMID- 10209457
TI  - Plasma endothelial-1 concentrations in patients with retinal vein occlusions.

PMID- 10209458
TI  - Endoscopically assisted gracilis harvest for use as a free and pedicled flap.
AB  - Endoscopic assistance in soft tissue surgery may prove to greatly aid in the
      improvement of cosmesis and reduction of morbidity in certain procedures. The
      scar produced from open gracilis harvest is the most common complaint following
      surgery. We present five cases of endoscopically assisted gracilis harvest for
      use as a neosphincter and in foot reconstruction. The operative technique is
      described.

PMID- 10209459
TI  - Malignant tumours of the maxillary complex: an 18-year review.
AB  - Over an 18-year period, 147 patients with malignant tumours involving the
      maxillary complex were treated in a combined head and neck clinic, of whom 50
      underwent surgery. There were 33 males and 17 females, the mean age was 57 years
      (range 11-87 years). The most common clinical presentations were either painful
      facial swelling, infraorbital anaesthesia, palatal ulceration or nasal
      obstruction. Preoperative investigations included EUA, biopsy and either CT or
      MRI scans. Of the 50 tumours, 62% were squamous cell carcinomas. Surgery
      consisted of either partial or total maxillectomy including craniofacial
      resection in nine patients. Reconstruction was by either split skin grafting or
      by free tissue transfer when the cranial contents had been exposed. Adjuvant
      radiotherapy was given in 82% of the patients. The mean follow-up was 5 years and
      59% of patients are alive and disease free. The 5-year local control rate was
      67%; it was greatly influenced by histological evidence of nerve invasion, local
      recurrence being the major cause of death. It was concluded that adequate
      surgical clearance, followed by planned postoperative radiotherapy, is the most
      effective treatment for malignant disease of the maxillary complex.

PMID- 10209460
TI  - Articulatory function and tongue mobility after surgery followed by radiotherapy
      for tongue and floor of the mouth cancer patients.
AB  - The aim of this study was to determine which of the following factors--size of
      the post-excisional defect, site of the defect and type of reconstruction-
      influence tongue mobility and articulation disorders after treatment for cancer
      of the tongue and floor of the mouth. A total of 60 patients, who had been
      evaluated at least 6 months after surgery followed by radiotherapy (60 Gy in 30
      fractions), were evaluated. According to the size of the post-excisional defect
      patients were divided into two groups: (1) defect less than 5 cm (35); (2) defect
      more than 5 cm (25). Based on the localisation of the defect patients were also
      divided into two groups: (1) anterior tongue and/or floor of the mouth (30); (2)
      lateral tongue and/or floor of the mouth (25) and tongue base (5). According to
      the type of reconstruction patients were divided into three groups: partly
      reconstructed (18); reconstructed with locally available tissue--local flaps
      (27); and with pectoralis major myocutaneous (PMMC) flaps (15). Articulation
      proficiency was assessed through Articulation Test and tongue mobility through
      Tongue Mobility Test. According to results of this study, type of reconstruction
      followed by size of post-excisional defect seemed to be the most influential
      factor in tongue mobility and articulation disorders after the tongue and floor
      of the mouth cancer treatment. Site of the defect has no influence.

PMID- 10209461
TI  - An anatomical study of the junction of the orbital septum and the levator
      aponeurosis in Orientals.
AB  - The anatomical relationships of the orbital septum and levator aponeurosis has
      been studied in 40 eyelids subjected to blepharoplasty and corrective ptosis
      surgery by dissection in 10 cadavers and in histological sections. The orbital
      septum originates from the arcus marginalis of the frontal bone and consists of
      two layers. The whitish outer (superficial) layer, containing vertically running
      vessels, descends just inside the orbicularis oculi muscle to interdigitate with
      the levator aponeurosis with loose connective tissue, then disperses inferiorly.
      The inner (deep) layer follows the superficial one initially, then reflects at
      the levator aponeurosis and continues posteriorly with the levator sheath. We
      reconfirmed Whitnall's original description that the levator sheath thickens to
      form the superior transverse ligament runs continuously inferiorly anterior to
      the levator aponeurosis and forms the inner layer of the orbital septum. This
      detailed anatomical analysis should assist in performing upper eyelid surgery
      such as the Oriental double fold operation or levator resection.

PMID- 10209462
TI  - Thermal injuries in autogenous tissue breast reconstruction.
AB  - We report on four patients with partial and full thickness burns following
      autogenous tissue breast reconstruction. Three burns were confined to the flap
      and one burn involved the flap and rim of adjacent skin. Heat sources included a
      heating pad (n = 3) and sunlight through a bathing suit (n = 1). The injuries
      occurred from 6 days to 4 years following the reconstruction. The burns were the
      result of impaired thermoregulatory capacity of transplanted tissue. All wounds
      healed with local wound care or debridement and skin grafting.

PMID- 10209463
TI  - Donor-site morbidity of the segmental rectus abdominis muscle flap.
AB  - The donor-site morbidity of the segmental rectus abdominis muscle flap was
      evaluated in 20 patients with an average follow-up time of 47 months. Our
      criteria were based on static and dynamic functional results including relaxation
      and hernia of the abdominal wall, aesthetic outcome and patient satisfaction. The
      dynamic functional tests of the abdominal wall showed good results corresponding
      to the reported minimal impairment of quality of life. There was one abdominal
      hernia after wound infection and secondary healing. There was no evidence of
      abdominal wall instability in any of the other patients. The aesthetic outcome
      was excellent when a transverse lower abdominal incision, asymmetrically
      elongated to the donor site, was used and moderate in the case of a paramedian
      vertical incision. Ninety-five per cent of the patients were completely satisfied
      or satisfied with the result at the donor site. In the segmental use of the free
      rectus abdominis flap a high degree of subjective patient satisfaction reflects
      the favourable outcome of our examinations. On the other hand there is a
      clinically significant functional donor-site defect of this flap. As this
      procedure is still widely used, and as its indication is closely linked to its
      absolute and relative donor-site defect, comparisons with the alternatives, e.g.
      the partial latissimus dorsi muscle flap, the extended gracilis muscle flap or
      the serratus anterior muscle flap will have to be made.

PMID- 10209464
TI  - Surgical management of hands in children with recessive dystrophic epidermolysis
      bullosa: use of allogeneic composite cultured skin grafts.
AB  - Recessive dystrophic epidermolysis bullosa (RDEB) is characterised by progressive
      childhood hand syndactyly and flexion contractures, which can be managed
      surgically but require split thickness autografts to facilitate satisfactory
      postoperative healing. We report on the partial substitution, for autografts, of
      improved composite cultured skin (CCS) allografts. The structure and preparation
      of these CCSs is outlined and their application in the course of 16 operations
      performed on 7 RDEB children with syndactyly and flexor contractures of fingers
      is described. Hand contractures were released and web spaces were covered with
      local flaps and split thickness autografts, while adjacent sides of the digits
      and other areas, as well as donor sites were generally grafted with CCS.
      Morphologic and functional results with CCS were judged to be good to excellent,
      the average time to recurrence was increased approximately 2-fold and smaller
      autografts needed to be used. In addition, healed CCS-treated donor sites could
      provide superior donor sites for further surgery.

PMID- 10209465
TI  - Treatment of arborising telangiectasia with pulsed tunable dye laser (SPTL-1b).
AB  - Arborising telangiectasia is a rare but distinct progressive condition of unknown
      aetiology. The vessels are subepidermal and measure less than 0.2 mm in diameter.
      Twenty-three patients with this condition, involving the lower limbs and in
      extensive cases the upper limbs and trunk, have been treated with the flash lamp
      pulsed tunable dye laser (SPTL-1b, Candela Laser Corp.). Retrospective review of
      17 of these patients, who have finished their treatment (average five sessions of
      therapy per patient, given at 3-4 monthly intervals), shows complete clearance of
      the telangiectasia in all cases. The mean follow-up time after the last session
      of treatment was 7 months. Temporary hyperpigmentation was seen in eight
      patients. Persistent pigmentary changes (one hyper- and one hypopigmentation)
      were noted in two patients. No evidence of scarring or change in skin texture was
      encountered. No progression or recurrence of telangiectasia was noted during the
      period of follow-up.

PMID- 10209466
TI  - The partial gluteus maximus musculocutaneous turnover flap. An alternative
      concept for simultaneous reconstruction of combined defects of the posterior
      perineum/sacrum and the posterior vaginal wall.
AB  - Three cases with posterior perineo-sacral defects are presented. One is a 57-year
      old white female following amputation of her rectum for carcinoma, radiation and
      chemotherapy with a significant residual sacral/perineal defect and loss of the
      posterior vaginal wall. The two other patients had radical pelvic exenteration
      after recurrent rectum carcinoma. A new myocutaneous turnover flap as a
      modification of the conventional gluteus maximus flap was designed to solve the
      particular reconstructive problems. The flap is based on branches of the inferior
      gluteal artery. The posterior cutaneous femoral nerve and the motor branches of
      the inferior gluteal nerve not leading into the muscle portion of the flap are
      left intact. The skin island can be used for vaginal reconstruction or can be de
      epithelialised to fill perineal cavities. This new flap eventually enabled the
      successful reconstruction of the posterior vaginal wall and appropriate
      sacral/perineal soft tissue coverage in the first case. In the other patients the
      flap was used to achieve closure of the deep through-and-through defect acutely
      in one case, and after a 3-week interval in the other.

PMID- 10209467
TI  - Dexamethasone treatment prior to reperfusion improves the survival of skin flaps
      subjected to secondary venous ischaemia.
AB  - The potential use of the anti-inflammatory glucocorticoid, dexamethasone, to
      treat ischaemic skin flaps prior to reperfusion was investigated. Island flaps
      were raised in rats, subjected to arteriovenous ischaemia for 2 h, normal blood
      flow for 24 h, secondary venous ischaemia for 4 h and secondary reperfusion for 7
      days. This sequence mimics the clinical sequence of free flap transfer followed
      by a subsequent venous thrombosis. Groups of 10 rats were administered with an
      intraperitoneal dose of either saline (controls) or dexamethasone (2.5 mg/kg) 30
      min before the end of the venous ischaemia. Compared with viability of 70.0% in
      controls, dexamethasone treatment increased viability significantly to 92.0% (P <
      0.01). In skin flap tissue harvested at 24 h reperfusion, dexamethasone treatment
      resulted in significant attenuation of tissue water content, tissue
      myeloperoxidase activity and tissue hydroperoxide levels. Thus the protective
      effect of this agent may be explained by the combined reduction of oedema
      formation, neutrophil infiltration and free radical production, respectively. We
      conclude that a single systemic dose of dexamethasone prior to reperfusion may be
      beneficial in treating skin flaps that have undergone secondary venous ischaemia.

PMID- 10209468
TI  - Venous drainage through bone marrow after replantation: an experimental study.
AB  - Venous drainage is vital for successful replantation, but it is not always
      possible to reconstruct because of missing or damaged veins. We devised an
      experimental model to study venous drainage through bone marrow while the new
      subcutaneous venous system regenerated. Adult male Wistar rats were placed into
      three groups. Group A rats had their hindlimbs amputated at the lower leg, but
      the tibia and sural and saphenous artery connections were preserved. Group B rats
      were prepared the same as Group A, except that a step-cut osteotomy was performed
      in the tibia. The bone ends were then realigned and kept in place with stainless
      steel wire. Group C rats were prepared the same as Group B, except that the ends
      of the bone were not aligned. All unoperated limbs served as controls for
      evaluations of blood flow. Experimental limbs were evaluated for skin colour and
      viability, blood flow and dye injection. Skin colour was investigated daily.
      Blood flow was measured postoperatively during three phases: immediate (up to 1
      h), early (from 1 h to 24 h), and late (from 1 day to 7 days after operation).
      Survival of limbs varied in Groups A and B, while all limbs in Group C necrosed
      by day 7. Blood flow was returning to near control (normal) levels by day 7 in
      Group A and B limbs. India ink was observed in the medullary cavity at day 7.
      After replantation, bone marrow plays a critical role in venous drainage until
      the subcutaneous venous drainage system regenerates.

PMID- 10209469
TI  - Time course of superoxide generation in reperfusion after arterial ischaemia and
      venous congestion.
AB  - In order to identify differences in superoxide (O2-) production after reperfusion
      following arterial ischaemia and venous congestion, we directly quantified O2- in
      the venous effluent from reperfused hindlimbs in the rabbit. Using a total of 20
      rabbit hindlimbs, we made hindlimb-reperfusion models by section of both soft
      tissue and bony structures exclusive of femoral vessels around the thighs and
      clamping of the artery alone (group A: n = 10) or vein alone (group V: n = 10) by
      microvascular clamp. A pilot study revealed that the critical time for venous
      congestion was 2 h. Accordingly, clamping was performed at 25 degrees C
      (normothermia) for 2 h. Sham operations were performed in the control (n = 7).
      Venous effluent blood samples from the femoral vein proximal to the clamping
      point were collected before reperfusion, and from 5 to 60 min after reperfusion
      at 5 min intervals. Effluent blood samples were used to quantify O2- using a
      chemiluminescence method using a derivative of luciferin. The time course of O2-
      production after reperfusion in group A and group V showed significant
      differences (P < 0.05), compared with the controls. There was no significant
      difference in the time course of O2- production in group A and that in group V.
      In the early reperfusion phase, no difference in O2- production was observed
      after arterial ischaemia or venous congestion. In future studies, we will test
      the contributions of free radicals by setting longer ischaemic times, longer
      reperfusion times, and studying secondary ischaemia.

PMID- 10209470
TI  - Ulnar nerve reconstruction with an expanded polytetrafluoroethylene conduit.
AB  - The ulnar nerve of a 22-year-old woman was reconstructed by expanded
      polytetrafluoroethylene (ePTFE) conduit, 141 days after nerve transection at the
      distal forearm level. A 2.9 cm nerve gap was bridged by a corrugated, 3.9 cm
      long, 6 mm diameter ePTFE tube. At final evaluation 3 years later the patient
      achieved excellent motor and sensory recovery. Exploration of the tube, at that
      time, showed macroscopically normal nerve inside the conduit.

PMID- 10209471
TI  - Leech-borne Serratia marcescens infection following complex hand injury.
AB  - Leeches are commonly used in the postoperative course of plastic surgical
      operations where there is venous congestion in a pedicled or free flap. They
      provide a temporary relief to venous engorgement whilst venous drainage is re
      established. It is known that leeches can carry Aeromonas hydrophila infection,
      and a second or third generation cephalosporin antibiotic has traditionally been
      given as prophylaxis against infection. We report a new observation that leeches
      can carry Serratia marcescens and give rise to clinically significant infection.
      The implication for prophylaxis and treatment of leech-associated cellulitis is
      discussed.

PMID- 10209472
TI  - Impossible harvest of the posterior interosseous artery flap: a report of an
      individualised salvage procedure.
AB  - Although the posterior interosseous artery flap represents a reliable technique
      to provide vascularised skin cover for the dorsum of the hand, the dissection of
      the flap is often very difficult because of anatomical variants. The weakest part
      of the vascularisation is the middle third of the posterior interosseous artery.
      Whenever it is discovered during the operation that such a flap is impossible to
      harvest, or likely to be unreliable, there is an immediate need to choose an
      alternative. Such a case is reported here. The individual anatomical situation
      allowed the dissection of a flap, the pedicle of which carried its blood supply
      from a perforating branch of the anterior interosseous artery. The technique
      described offers an individual solution to the problem of skin coverage when the
      harvest of the posterior interosseous artery is impossible.

PMID- 10209473
TI  - Squamous cell carcinoma of the tongue in a patient with Rothmund-Thomson
      syndrome.
AB  - Rothmund-Thomson syndrome is a rare autosomal recessive genodermatosis
      characterised by poikilodermatous skin changes that appear in childhood. Patients
      exhibit variable additional features including juvenile cataracts, skeletal
      abnormalities and a higher than expected incidence of malignancies. We report a
      case of squamous cell carcinoma of the tongue in a 37-year-old Rothmund-Thomson
      syndrome patient and review the natural history of this rare disease, given that
      the patient was diagnosed with Rothmund-Thomson syndrome at the age of 8 years
      and was first reported in 1975.

PMID- 10209474
TI  - Reconstruction of an extensive scalp defect.

PMID- 10209475
TI  - The digital second opinion.

PMID- 10209476
TI  - The distally based island posterior interosseous flap.

PMID- 10209477
TI  - A 5-year review of islanded distally based fasciocutaneous flaps on the lower
      limb.

PMID- 10209478
TI  - Distally based flaps--contraindicated in the obese?

PMID- 10209479
TI  - A seat belt injury to the female breast.

PMID- 10209480
TI  - Markers of melanocytic tumour progression.
AB  - Melanoma progression markers can be defined as molecules with a preferential
      expression in one or a few stages of melanocytic tumour development. These
      molecules include growth factors, growth factors receptors, adhesion molecules,
      proteases and related components. Immunohistochemical studies suggest that some
      of these molecules are useful as prognostic markers in melanoma patients. In
      cutaneous melanocytic lesions, the distribution of E-cadherin, a member of a
      family of cell adhesion molecules that mediate cell-cell interactions by means of
      Ca2+ dependent, homophilic interactions, appears to be complex. Although a
      decrease of E-cadherin would be expected with invasive tumour growth in advanced
      primary melanoma and eventually in metastasis, surprisingly an increase is found,
      whereas alpha- and beta-catenin, (cytoplasmic) molecules functionally associated
      with E-cadherin, are detected in all benign and malignant lesions. A possible
      interpretation includes a difference in the morphogenesis and function of
      melanocytic cells, compared with epithelial cells. Further research is needed to
      clarify the role of E-cadherin/catenin during melanoma progression.

PMID- 10209481
TI  - Gap junctions in normal and neoplastic mammary gland.
AB  - Progress in the characterization of gap junctions and their constituent connexin
      sub-units is leading to a greater understanding of the structure, function, and
      regulation of this cell-cell communication channel. Although much of the
      experimental evidence generated to date is correlative, recent work utilizing
      reverse genetic approaches to manipulate connexin gene function has provided
      direct evidence that intercellular communication via gap junctions plays key
      roles in development, cellular differentiation, and organogenesis. Pathogenic
      mutations in human connexin genes have now been identified. Furthermore, a
      considerable body of experimental evidence correlates a loss of junctional
      communication with progression to a malignant phenotype. Although the cell
      biology of the mammary gland has been extensively studied, the role(s) of gap
      junctions in the development, differentiation, and maintenance of this tissue are
      unknown. Gap junctions were first reported in the mammary gland following freeze
      fracture and electron microscopic analyses. The development of anti-connexin
      antibodies and the cloning of individual connexin isoforms have enabled this work
      to be extended, but there are contradictory reports in the temporal expression
      patterns of these proteins within mammary epithelium. In addition, a recent
      report in this Journal has implied by immunocytochemistry that there is up
      regulation of connexin protein in some human breast tumours, a novel observation
      which may be inconsistent with the proposed tumour suppressor role for gap
      junctions.

PMID- 10209482
TI  - E-cadherin/catenin complex in benign and malignant melanocytic lesions.
AB  - E-cadherin is a calcium-dependent cell-cell adhesion molecule expressed by
      melanocytes and responsible for their adhesion to keratinocytes in vitro. In this
      study, the expression of E-cadherin and its associated cytoplasmic proteins alpha
      , beta-, and gamma-catenin was evaluated in melanocytic lesions by
      immunohistochemistry. E-cadherin expression was evaluated in 70 malignant
      melanomas and the catenins in 35 of these specimens. Twenty benign melanocytic
      naevi were also evaluated for E-cadherin and catenin expression. In normal
      epidermis, E-cadherin/catenin immunostaining was localized at the intercellular
      borders. In melanomas, a differential loss of E-cadherin expression was observed.
      Membranous E-cadherin staining was absent in dermal nests of melanomas in their
      radial growth phase and in Clark level II and III lesions, whereas it was present
      in a high proportion of melanomas in their vertical growth phase, in Clark level
      IV and V lesions and in metastasizing melanomas. In contrast, superficial
      compartments of naevi showed membranous E-cadherin immunoreactivity and
      junctional naevus cell nests displayed heterogeneous or diffuse cytoplasmic
      staining. Cytoplasmic alpha- and beta-catenin, but not gamma-catenin staining
      were detected in all benign and malignant lesions. These findings indicate that
      qualitative changes in the expression and cellular localization of E-cadherin and
      of alpha-, beta-, and gamma-catenin occur in melanocytic lesions and may reflect
      different stages in their progression.

PMID- 10209483
TI  - Genetic analysis of 53 lymph node-negative breast carcinomas by CGH and relation
      to clinical, pathological, morphometric, and DNA cytometric prognostic factors.
AB  - Within the subgroup of lymph node-negative breast cancers, there is a need for
      accurate prognostic indicators to select high-risk patients. Comparative genomic
      hybridization (CGH) provides an opportunity to screen the whole genome for
      chromosomal aberrations which may be associated with poor clinical outcome. The
      results of CGH analysis of 53 lymph node-negative breast carcinomas are presented
      and correlated with a set of clinico-pathological and cytometric features with
      strong prognostic value. The most frequent chromosomal gains were, in descending
      order of frequency, 8q, 1q, Xq, 5q, 4q, and 3q. Recurring losses were observed at
      chromosomal arms 19p, 1p, 17p, 22q, 4q, and 8p. There was not a single, unique
      combination of chromosomal aberrations, but gains of 1q and 8q were frequently
      observed simultaneously (15/53 cases). DNA aneuploid tumours harboured more gains
      than DNA diploid tumours, but there was no correlation between the total number
      of events per tumour detected by CGH and any of the prognostic features. Of the
      many chromosomal aberrations found, only gains of chromosome 8q were strongly
      correlated with high values of mean nuclear area. A clearer picture was obtained
      when comparing only those cases which, according to their cytometric and
      morphometric features, had either the worst or the best prognosis. Gains occurred
      mainly in the 'poor prognostic features' group, in particular at 8q, 11q13, 17q,
      and 20q. It is hypothesized that these gains could be late, progression-related
      events and may be associated with aggressive clinical behaviour. These four
      chromosomal regions may therefore be of potential prognostic value. Correlation
      with real follow-up data will enable us better to identify those patients who
      have a high risk of recurrence within the subgroup of lymph node-negative breast
      cancer patients.

PMID- 10209484
TI  - Clonal analysis of sporadic pancreatic endocrine tumours.
AB  - The clonal composition of 34 benign and malignant sporadic pancreatic endocrine
      tumours (PETs) of female patients was studied using a sensitive polymerase chain
      reaction (PCR)-mediated non-isotopic clonality analysis, which is based on the
      inactivation patterns of polymorphic X-linked genes encoding the androgen
      receptor (AR) and phosphoglycerate kinase (PGK-1) proteins. Predigestion of DNA
      with the methylation-sensitive restriction endonuclease Hpa II permitted
      selective PCR amplification of the methylated (uncleaved) allele. Amplification
      was successful in 27 of 34 samples. Twenty patient samples were heterozygous for
      the AR microsatellite region or Bst XI polymorphic site of the PGK-1 gene,
      permitting analysis of clonality. A monoclonal pattern of X-chromosome
      inactivation was found in 7 of 20 PETs (35 per cent), since DNA pretreatment with
      Hpa II blocked amplification of one of the two AR or PGK-1 alleles. One
      additional tumour exhibited an oligoclonal inactivation pattern and two others a
      loss of heterozygosity (LOH) at the AR locus, indicative of monoclonality. A
      random pattern of X-chromosome inactivation and polyclonal cellular composition
      was observed in the remaining ten PETs (50 per cent). When comparing informative
      benign and malignant PETs, only 2/7 (29 per cent) benign tumours showed a
      monoclonal pattern and 8/13 (61 per cent) malignant tumours a monoclonal (5),
      oligoclonal (1), or LOH (2) pattern. The clonal composition of PETs was not
      associated with a particular growth pattern, proliferation index or
      immunohistochemical expression pattern. These findings suggest that PETs might
      initially represent poly-/oligoclonal neoplastic lesions which are eventually
      outgrown by a single, more aggressive cell clone with the potential for invasive
      growth and metastatic spread.

PMID- 10209486
TI  - Infrequent bax gene mutations in B-cell lymphomas.
AB  - Mutation of the bax gene has been reported previously in lymphoid cell lines. In
      vitro experiments have shown that alterations in promoter and coding sequences of
      the gene abolish its apoptosis initiation function, which is considered crucial
      for tumour development. To assess bax gene mutations in lymphomagenesis,
      polymerase chain reaction-based single strand conformation polymorphism analysis
      (PCR-SSCP) and direct sequencing were used to detect altered sequences in the
      promoter region and all the six exons and their flanking sequences of the gene.
      Nodal and extranodal B-cell lymphomas (n = 112) including follicular lymphoma,
      mantle cell lymphoma, diffuse large B-cell lymphoma, splenic marginal zone B-cell
      lymphoma and low- and high-grade mucosa-associated lymphoid tissue (MALT)
      lymphomas were studied. Sequence alterations were found in 11 cases. Nine also
      showed the same altered sequences in corresponding non-tumour control tissue
      samples, indicating polymorphism. In the remaining two cases, sequence
      alterations (in exons 3 and 6) which altered the bax open reading frame were
      observed only in tumour tissues, indicating tumour-specific point mutation. These
      results suggest that inhibition of apoptosis through bax gene mutations is
      unlikely to be a common event in B-cell lymphoma, at least in the major types of
      nodal and extranodal B-cell lymphomas.

PMID- 10209485
TI  - Monocyte chemoattractant protein-1 (MCP-1) expression in primary
      lymphoepithelioma-like carcinomas (LELCs) of the lung.
AB  - Lymphoepithelioma-like carcinoma (LELC) of the lung is a recently recognized
      primary non-small cell lung carcinoma with distinct clinicopathological features
      and an aetiological association with Epstein-Barr virus (EBV) infection. The
      tumour consists of clusters and sheets of poorly or undifferentiated tumour cells
      in close association with numerous mononuclear inflammatory cells, including a
      rich component of tumour-associated macrophages (TAMs). To investigate the
      molecular mechanism leading to the TAM-rich stroma, the expression of a monocyte
      specific chemotactic and activating factor, monocyte chemoattractant protein-1
      (MCP-1), was studied by reverse transcriptase-polymerase chain reaction (RT-PCR)
      and in situ hybridization (ISH), and the presence of TAMs was demonstrated by
      immunohistochemistry in nine LELCs. The results were compared with those found in
      17 conventional non-small cell lung carcinomas. RT-PCR showed specific MCP-1
      amplification in both LELCs and non-LELCs, but ISH demonstrated a unique and
      extensive expression of MCP-1 transcripts by the tumour cells of LELCs only,
      while TAMs, stromal fibroblasts, and endothelial cells formed the major source of
      MCP-1 in non-LELCs. TAMs in LELCs were more abundant and showed a close
      topographical relationship with the MCP-1-expressing tumour cells. The results
      indicate that tumour cell expression of MCP-1 in LELCs is an important mechanism
      contributing to their distinctive morphological features. This is the first study
      that demonstrates the in vivo upregulation of a monocyte-specific chemokine by
      EBV-related carcinomas, illustrating an interesting aspect of tumour biology in
      EBV-related neoplasms.

PMID- 10209487
TI  - Expression of CD44 splice variant v10 in Hodgkin's disease is associated with
      aggressive behaviour and high risk of relapse.
AB  - Expression of CD44 isoforms has been shown to correlate with the progression and
      prognosis of some malignant tumours. The aim of this study was to investigate the
      expression of CD44 standard (CD44s) and CD44 splice variants (CD44v) v5, v6, and
      v10 in lymph node specimens from patients with nodular sclerosing Hodgkin's
      disease (NSHD), with or without initial bone marrow involvement and with or
      without relapse. Specimens were studied by immunohistochemistry to determine
      CD44s and CD44v in Hodgkin- and Reed-Sternberg (HRS) cells. For validation of the
      immunohistochemical of detection of CD44v10 in paraffin-embedded samples,
      selected cases were analysed in parallel immunohistochemically using fresh frozen
      material and by reverse transcription-polymerase chain reaction (RT-PCR). There
      was high expression of CD44 isoforms containing the variant exon v10 selectively
      in HRS cells of patients with relapse within 2-3 years or with initial bone
      marrow involvement. In patients without relapse, however, no or only very few HRS
      cells were positive. These differences were statistically highly significant (p <
      or = 0.001), whereas evaluation of CD44s, CD44v5, and v6 expression revealed no
      marked differences. It is concluded that evaluation of CD44v10 expression could
      serve as a new prognostic marker in NSHD. These results are considered to be of
      sufficient importance to initiate a large multi-institutional study for
      confirmation; furthermore, they might suggest causal involvement of CD44v10 in
      the progression of NSHD.

PMID- 10209488
TI  - Interaction between endothelial cells and the secreted cytokine drives the fate
      of an IL4- or an IL5-transduced tumour.
AB  - Injection of interleukin-4 (IL4) gene-transduced tumour cells into syngeneic
      immunocompetent mice resulted in tumour rejection in which a key role for
      eosinophils was suggested. To evaluate whether IL5 inhibits tumour growth by
      selectively inducing eosinophil recruitment and activation, a poorly
      differentiated mammary adenocarcinoma cell line (TSA) was transfected with the
      IL5 gene and the cells secreting IL5 (TSA-IL5) were injected subcutaneously
      (s.c.) in syngeneic mice. The oncogenicity of TSA-IL5 was compared with that
      exhibited by TSA cells transfected with the IL4 gene (TSA-IL4) and with the
      neomycin resistance gene only (TSA-neo). At progressive times after subcutaneous
      challenge, tumour growth areas were studied histologically, ultrastructurally,
      and immunohistochemically to identify the reactive cells, visualize tumour
      vessels, and detect the cytokines and chemokines involved in the anti-tumour
      reaction. Both the morphological and the functional data showed that TSA-IL5,
      despite the large eosinophil infiltrate, grew progressively like TSA-neo,
      suggesting that eosinophils per se do not play a crucial role in TSA tumour
      rejection. Furthermore, our data indicate that the rejection of TSA-IL4 depends
      on the IL4-induced expression of VCAM-1 and MCP-1 by endothelial cells. MCP-1
      together with VCAM-1 results in recruitment and activation of basophils, mast
      cells, and macrophages, and hence a pro-inflammatory cytokine cascade that
      initially favours the influx and activation of neutrophils and finally tumour
      rejection. In this context, the rejection of TSA-IL4 seems to involve a variety
      of reactive cells and rests on a continuous cross-talk between basophils, mast
      cells, macrophages, CD8-positive lymphocytes, and granulocyte subsets, mostly
      neutrophils.

PMID- 10209489
TI  - The MUC6 secretory mucin gene is expressed in a wide variety of epithelial
      tissues.
AB  - Secretory mucins play an important role in the cytoprotection of epithelial
      surfaces and are used as tumour markers in a variety of cancers. The MUC6
      secretory mucin was originally isolated from a gastric cDNA library. The aim was
      to determine the specific type and location of MUC6 mucin gene expression in a
      wide range of human adult and fetal epithelial tissues. In situ hybridization,
      RNA analysis, and immunohistochemistry were used to quantify and localize mucin
      gene expression. The data obtained show that MUC6 is highly expressed in gastric
      mucosa, duodenal Brunner's glands, gall bladder, seminal vesicle, pancreatic
      centroacinar cells and ducts, and periductal glands of the common bile duct;
      focal expression is seen in basal endometrial and endocervical glands. MUC6
      epitopes were also highly expressed in 7/10 pancreatic cancers and 7/10
      cholangiocarcinomas and focally expressed in 4/10 endocervical adenocarcinomas.
      Expression of MUC6 occurs early in fetal development and was observed in
      Brunner's glands and pancreatic ducts at 18-19 weeks and in gastric glands at 20
      weeks' gestation. The tissue distribution of the MUC6 secretory mucin indicates
      that it may function to protect epithelial tissues from a wide range of
      substances. Expression of MUC6 is frequently preserved in pancreatic and bile
      duct adenocarcinomas, but it is only sparsely expressed in endocervical
      carcinomas.

PMID- 10209490
TI  - Cycling activity of benign prostatic epithelial cells during long-term androgen
      blockade: evidence for self-renewal of luminal cells.
AB  - Combined androgen blockade (CAB) therapy (LHRH agonist and flutamide) for 6
      months leads to marked regressive changes of the prostate gland. This is
      associated with a reduction in the ratio of luminal to basal cells in the
      peripheral zone (PZ) in hyperplastic glands of the transitional zone (TZ). To
      examine the cycling activity of luminal and basal cells, double immunostaining
      was performed. For precise definition of basal cells, the basal cell-specific
      antibody 34 beta E12 was used, while cycling cells were identified by the MIB-1
      antibody. In 6-month-treated specimens, the fraction of cycling luminal cells
      increased from 0.3 to 2.5 per cent in the PZ and from 0.2 to 3.9 per cent in the
      TZ. This was associated with an inversion of the ratio of MIB-1-labelled luminal
      to basal cells, with values of 5.7:1 (PZ) and 3.9:1 (TZ), compared with 1:4 (PZ)
      and 1:5 (TZ) in untreated specimens. The predominance continued for at least 11
      years of CAB. The findings strongly suggest that luminal cells are capable of
      self-renewal under conditions of low androgen levels. The substantial decrease of
      prostatic volume on long-term CAB implies that cell loss outweighs cell
      proliferation.

PMID- 10209491
TI  - Co-localization of immunoreactive transforming growth factor-beta 1 and decorin
      in bronchial biopsies from asthmatic and normal subjects.
AB  - Airway wall remodelling is an established pathological feature of asthma but its
      causes are not well understood. One cytokine of potential relevance is
      transforming growth factor-beta1 (TGF-beta 1). The immunolocalization of TGF-beta
      1 and of its small binding proteoglycan decorin have been examined in the airways
      of normal subjects and atopic asthmatics. Bronchial biopsy specimens were
      obtained by fibreoptic bronchoscopy, processed into glycolmethacrylate resin, and
      stained immunohistochemically using specific antibodies. Immunoreactive TGF-beta
      1 was principally localized extracellularly in association with subepithelial
      connective tissue. Some staining of bronchial epithelial cells was also evident,
      but otherwise there was little intracellular staining. The overall pattern of
      immunohistochemical staining was indistinguishable in biopsy specimens from
      asthmatic and control subjects. Comparison of adjacent sections demonstrated the
      co-localization of immunoreactivity for TGF-beta 1 and decorin in the mucosa. It
      is concluded that immunoreactive TGF-beta 1 in human airways is principally
      extracellular and that matrix-associated TGF-beta 1 is likely to be bound at
      least in part to decorin. This interaction may provide a reservoir of TGF-beta 1
      that can be released in an active form in response to appropriate stimuli.

PMID- 10209492
TI  - Expression of nitric oxide synthases and formation of nitrotyrosine and reactive
      oxygen species in inflammatory bowel disease.
AB  - Nitric oxide (NO) and reactive oxygen species (ROS) are important mediators in
      the pathogenesis of inflammatory bowel disease (IBD). NO in IBD can be either
      harmful or protective. NO can react with superoxide anions (O2.-), yielding the
      toxic oxidizing agent peroxynitrite (ONOO-). Peroxynitrite induces nitration of
      tyrosine residues (nitrotyrosine), leading to changes of protein structure and
      function. The aim of this study was to identify the cellular source of inducible
      nitric oxide synthase (iNOS) and to localize superoxide anion-producing cells in
      mucosal biopsies from patients with active IBD. Additional studies were performed
      to look at nitrotyrosine formation as a measure of peroxynitrite-mediated tissue
      damage. For this, antibodies against iNOS, endothelial NOS (eNOS), and
      nitrotyrosine were used. ROS-producing cells were detected cytochemically.
      Inflamed mucosa of patients with active IBD showed intense iNOS staining in the
      epithelial cells. iNOS could not be detected in non-inflamed mucosa of IBD
      patients and control subjects. eNOS was present in blood vessels, without any
      difference in the staining intensity between IBD patients and control subjects.
      ROS-producing cells were increased in the lamina propria of IBD patients; a
      fraction of these cells were CD15-positive. Nitrotyrosine formation was found on
      ROS-positive cells. These results show that iNOS is induced in epithelial cells
      from patients with active ulcerative colitis or Crohn's disease. Nitration of
      proteins was detected only on the ROS-producing cells at some distance from the
      iNOS-producing epithelial cells. These findings indicate that tissue damage
      during active inflammation in IBD patients is probably more related to ROS
      producing cells than to NO. One may speculate that NO has a protective role when
      during active inflammation other mucosal defence systems are impaired.

PMID- 10209493
TI  - Differential expression of cell adhesion molecules in inflamed appendix:
      correlation with clinical stage.
AB  - The diagnosis of 'early inflamed', 'recurrent' or 'sub-acute' appendicitis is
      often difficult and accompanied by controversies between clinical data,
      histological findings, and their interpretation. The expression of the
      intercellular cell adhesion molecule-1 (ICAM-1), the vascular cell adhesion
      molecule-1 (VCAM-1), and E-selectin has been studied in 61 appendicectomy
      specimens for possible use as a diagnostic tool. This study demonstrates a
      different expression of CAM by endothelial (EC) and mesothelial cells (MC) in the
      various stages of appendicitis, with early E-selectin and ICAM-1 expression in
      EC, followed by VCAM-1 in EC and MC. Appendices from patients with prolonged
      clinical symptoms defined by clinicians as 'chronic' appendicitis showed VCAM-1
      expression and occasionally weak expression of E-selectin in EC. In several
      cases, discrepancies were found between the pre-operative 'clinical' diagnosis,
      the histomorphological findings, and the immunohistological results. In this
      context, the expression of E-selectin and VCAM-1 in comparison with the
      histological features has potential significance in the diagnosis of 'early
      acute', 'sub-acute' or 'recurrent' appendicitis. In addition, a correlation was
      demonstrated between the histological stages of appendicitis and the kinetics of
      CAM expression. The study also indicates that the time course of E-selectin
      expression in vivo is longer than is suggested from in vitro data.

PMID- 10209494
TI  - Apoptosis and cell proliferation in biliary atresia.
AB  - Biliary atresia (BA), which is thought to result from progressive destruction of
      the bile ducts by a necroinflammatory process, is the most common cause of
      obstructive jaundice in infancy. Abnormalities in the cell turnover of
      remodelling ductal plates are considered one of the important aetiological
      factors in this disorder, but little work has been done on this topic. Programmed
      cell death or apoptosis was therefore examined by TdT-mediated dUTP biotin nick
      end labelling (TUNEL) and cell proliferation by Ki67 immunostaining in 34 cases
      of BA. The results were compared with normal control liver (five cases) and
      congenital dilatation of the bile ducts (CDB, five cases) in order to study the
      cell turnover or tissue dynamics of BA. The TUNEL labelling index (LI) in bile
      ducts (48.9 +/- 13.2 per cent) was significantly higher than that of the control
      normal liver (3.6 +/- 2.8 per cent) and of CDB (2.5 +/- 5.1 per cent). The Ki67
      LI in the bile ducts of BA (15.0 +/- 5.57 per cent) was also significantly higher
      than that of CDB (8.6 +/- 5.4 per cent). No significant differences of the TUNEL
      and Ki67 LIs in hepatocytes were, however, observed between BA, CDB, and normal
      liver. The TUNEL LI was significantly higher than the Ki67 LI in the bile ducts
      of BA. BA is therefore associated with increased and disorganized cell turnover
      of the bile ducts, which is related to malformation of the ductal plate or
      abnormal bile duct development.

PMID- 10209495
TI  - A novel EWS-ERG rearrangement generating two hybrid mRNAs in a peripheral
      primitive neuroectodermal tumour (pPNET) with a t(15;22) translocation.
AB  - The occurrence of a t(15;22) translocation in a peripheral primitive
      neuroectodermal tumour (pPNET) has been previously reported. Molecular
      examination revealed the presence in tumour mRNA of two hybrid transcripts
      containing the 5' portion of the EWS gene fused to the 3' portion of the ERG
      gene. Sequence analyses indicated that both aberrant mRNAs most likely originated
      from the same rearrangement, which produced different hybrid isoforms due to the
      presence of an alternatively spliced exon in the ERG gene. To the authors'
      knowledge, this is the first report of the detection of two hybrid EWS-ERG mRNAs
      within the same tumour.

PMID- 10209496
TI  - Smoking cessation guidelines for health professionals. A guide to effective
      smoking cessation interventions for the health care system. Health Education
      Authority.

PMID- 10209497
TI  - Eotaxin and asthma: some answers, more questions.

PMID- 10209498
TI  - Autoantibodies against C1q: view on clinical relevance and pathogenic role.

PMID- 10209499
TI  - Age-dependent altered proportions in subpopulations of tonsillar lymphocytes.
AB  - Age-related changes in functional subsets of lymphocytes may influence the
      potential to build up immune responses. In particular, the capacity of tonsillar
      lymphocytes to counter infections may be altered during ageing. In order to
      address this question we investigated the proportional distribution of several
      subsets of tonsillar T and B cells with regard to ageing. Tonsils were derived
      from 119 patients between 2 and 65 years of age. Lymphocyte subsets were
      monitored by three-colour fluorescence of relevant CD markers in flow cytometry.
      As a general tendency the percentage of CD3+ T cells steadily increased whereas
      that of CD19+ B cells decreased at the same time. No significant differences were
      observed between lymphocytes of patients with and without inflammatory history of
      the tonsils. The percentage of CD8+ T cells declined whereas that of CD4+ T cells
      increased during the same time span. CD45RA+ T cells increased during the first
      two decades of life and gradually decreased thereafter. In contrast, CD45RO+ T
      cells showed an opposite trend. No differences were seen in the population of CD3
      /CD56+ natural killer (NK) cells. The mature B cell marker CD40 showed no
      significant changes during ageing. However, CD38+ B cells, representing B cells
      of late maturation stages, dramatically declined up to the age of 65. In a
      similar manner the CD5+ subpopulation of B cells decreased during ageing.
      Substantial changes in major tonsillar T and B cell populations as shown in this
      study may have an impact on the ageing process of the immune system.

PMID- 10209500
TI  - Vitamin D, thyroid hormones and muscle mass influence natural killer (NK) innate
      immunity in healthy nonagenarians and centenarians.
AB  - Increasing evidence has demonstrated that the immune system closely interacts
      with other physiological systems, whose communications are mediated by
      circulating cytokines and hormones. The aim of our study was to test whether the
      number and cytolytic activity of NK cells in a group of relatively healthy
      Italian nonagenarians and centenarians were affected by the modifications of
      endocrine, metabolic and functional parameters that occur during ageing. Because
      of the extreme age of the study population, a cross-sectional analysis was
      performed. This study revealed that the group of oldest subjects with the highest
      number of NK cells and the best preserved cytolytic function also presented a
      preserved metabolism of thyroid hormones and vitamin D and integrity of muscle
      mass. In fact, the NK cell number and/or cytolytic activity of healthy subjects >
      90 years old was positively associated with serum levels of vitamin D, while T3,
      FT4, i-PTH hormones and lean body mass were associated only with NK cell number.
      In conclusion, our results stress the paramount importance of nutritional
      evaluation in the clinical assessment of elderly people.

PMID- 10209501
TI  - Immunomodulation by vitamin B12: augmentation of CD8+ T lymphocytes and natural
      killer (NK) cell activity in vitamin B12-deficient patients by methyl-B12
      treatment.
AB  - It has been suggested that vitamin B12 (vit.B12) plays an important role in
      immune system regulation, but the details are still obscure. In order to examine
      the action of vit.B12 on cells of the human immune system, lymphocyte
      subpopulations and NK cell activity were evaluated in 11 patients with vit.B12
      deficiency anaemia and in 13 control subjects. Decreases in the number of
      lymphocytes and CD8+ cells and in the proportion of CD4+ cells, an abnormally
      high CD4/CD8 ratio, and suppressed NK cell activity were noted in patients
      compared with control subjects. In all 11 patients and eight control subjects,
      these immune parameters were evaluated before and after methyl-B12 injection. The
      lymphocyte counts and number of CD8+ cells increased both in patients and in
      control subjects. The high CD4/CD8 ratio and suppressed NK cell activity were
      improved by methyl-B12 treatment. Augmentation of CD3-CD16+ cells occurred in
      patients after methyl-B12 treatment. In contrast, antibody-dependent cell
      mediated cytotoxicity (ADCC) activity, lectin-stimulated lymphocyte blast
      formation, and serum levels of immunoglobulins were not changed by methyl-B12
      treatment. These results indicate that vit.B12 might play an important role in
      cellular immunity, especially relativing to CD8+ cells and the NK cell system,
      which suggests effects on cytotoxic cells. We conclude that vit.B12 acts as an
      immunomodulator for cellular immunity.

PMID- 10209502
TI  - The antigen-presenting environment in normal and human papillomavirus (HPV)
      related premalignant cervical epithelium.
AB  - The activation of HPV-specific T cells within the cervical microenvironment is
      likely to play an important part in the natural history of cervical
      intraepithelial neoplasia (CIN). The extent and the type of T cell activation
      will depend critically on the expression of MHC, costimulatory cell surface
      molecules and cytokines by keratinocytes and Langerhans cells within the cervical
      lesion. Expression of MHC class II (HLA-A-DR and -DQ), costimulatory/adhesion
      molecules (CD11a/18, CD50, CD54, CD58 and CD86) and cytokines (tumour necrosis
      factor-alpha (TNF-alpha) and IL-10) was therefore investigated by
      immunohistochemistry in normal squamous epithelium (n = 12), low-grade (n = 23)
      and high-grade (n = 18) squamous intraepithelial lesions of the cervix. CIN
      progression was associated with de novo expression of HLA-DR and CD54, and
      increased expression of CD58 by keratinocytes. However, significantly, there was
      no expression of any adhesion/costimulation molecule by epithelial Langerhans
      cells in any cervical biopsy studied. Furthermore, TNF-alpha, a potent activator
      of Langerhans cells, was expressed constitutively by basal keratinocytes in
      normal cervix (12+/12). but expression of this cytokine was absent in a number of
      CIN samples (20+/23 for low-grade, 12+/18 for high-grade CIN). Conversely, the
      suppressive cytokine IL-10 was absent in normal epithelium (0+/12), but was up
      regulated in a number of CIN lesions (12+/23 for low-grade; 8+/18 for high-grade
      CIN). The restricted expression of costimulation/adhesion molecules and the
      nature of the cytokine microenvironment within the epithelium may act to limit
      effective immune responses in some CIN lesions.

PMID- 10209503
TI  - Binding of tumour necrosis factor-alpha (TNF-alpha) to TNF-RI induces caspase(s)
      dependent apoptosis in human cholangiocarcinoma cell lines.
AB  - Cholangiocarcinoma (CCA), a tumour of the bile duct epithelium, occurs with a
      higher incidence in South-east Asian countries than in Europe and North America.
      The prognosis is poor, due to the unavailability of early diagnosis and the
      tumours being relatively resistant to chemotherapy. In the present study one of
      the fatal routes of this tumour was studied. This death was stimulated by TNF
      alpha. TNF-alpha at a concentration of 760 pg/ml and 100 pg/ml in the presence of
      1 microgram/ml actinomycin D induced 50% cell death of the two established human
      cholangiocarcinoma cell lines HuCCA-1 and HuCCA-INu, respectively. Preincubation
      of both cell lines with MoAb to TNF-RI or TNF-RII before TNF-alpha treatment
      showed that only the MoAb specific to TNF-RI inhibited death. The death of these
      two cell lines was proved to be apoptosis. Western blot analysis of extracts from
      both cell lines demonstrated a cleavage of poly (ADP-ribose) polymerase (PARP)
      within 6-8 h following TNF-alpha treatment. The degradation of PARP was prevented
      by a MoAb to TNF-RI indicating that the TNF-RI but not TNF-RII was involved in
      TNF-induced apoptosis in these two human cholangiocarcinoma cell lines. Moreover,
      peptide inhibitor for caspase II subfamily, Ac-DEVD-CHO, reduced the cytolysis of
      TNF-alpha-treated cholangiocarcinoma cells. The inhibitor also prevented
      degradation of PARP. These results indicate that the interaction between TNF
      alpha and TNF-RI alone generated a sufficient signal to activate a caspase II
      subfamily-dependent apoptosis in human cholangiocarcinoma cell lines.

PMID- 10209504
TI  - Bladder cancer immunogenicity: expression of CD80 and CD86 is insufficient to
      allow primary CD4+ T cell activation in vitro.
AB  - Transitional cell carcinomas (TCC) of the urinary bladder are known to express
      proteins which can yield potentially immunogenic peptide epitopes for expression
      in the context of cell surface class I or class II MHC antigens. However,
      additional costimulatory ligands must also be expressed before such a cell might
      directly induce full activation and proliferation of resting, antigen-specific T
      lymphocytes. Intravesical therapy might be used to manipulate T cell
      costimulation in order to promote specific rejection of TCC cells. This in vitro
      study examined the potential of such a strategy by transfection of the
      prototypical TCC line J82 with the important costimulatory molecules CD80 (B7-1)
      and CD86 (B7-2). Untransfected J82 cells expressed class I and II MHC antigens, a
      range of cell adhesion molecules, though did not induce T cell proliferation in a
      robust, allogeneic co-culture system. Transfected J82 cells expressed CD80 or
      CD86 at levels comparable to an antigen-presenting B cell line. Furthermore,
      functional surface expression of CD80 and CD86 was demonstrated in a mitogen
      dependent assay of costimulation. However, neither CD80+ nor CD86+ transfectant
      J82 cells could induce significant proliferation of antigen-specific CD4+ T
      cells. Further analysis showed that bystander J82 cells could inhibit independent
      T cell activation in an effect dependent on direct cell contact. This inhibitory
      effect was associated with increased cell death in the responding lymphocyte
      population and is concordant with surface expression of CD95L by the J82 cell
      line.

PMID- 10209505
TI  - Surface phenotype analysis of CD16+ monocytes from leukapheresis collections for
      peripheral blood progenitors.
AB  - In peripheral blood progenitor cell (PBPC) collections from patients with solid
      tumour or haematological malignancy, monocytes were separated into two
      subpopulations. The majority of monocytes expressed CD14 at a high density
      without CD16 antigen (the CD14+CD16- monocytes). The remaining monocytes co
      expressed CD14 and CD16 (the CD14+CD16+ monocytes). These CD14+CD16+ monocytes
      amounted to 20.6 +/- 15.8%, while those in peripheral blood (PB) obtained from
      healthy volunteers were 7.3 +/- 3.1% (P < 0.05). When subdividing the CD14+CD16+
      monocytes into CD14brightCD16dim and CD14dimCD16bright cells, both populations
      were found to be increased in PBPC collections. Since typical CD14+CD16+
      monocytes are the CD14dimCD16bright population, we compared the additional
      surface antigens on CD14dimCD16bright monocytes with those of CD14+CD16-
      monocytes. In PBPC collections, the CD14dimCD16bright monocytes exhibited lower
      levels of CD11b, CD15, CD33 and CD38 expression and higher levels of CD4, CD11a,
      CD11c and MHC class II, and also revealed a higher percentage of CD4+ cells and a
      lower percentage of CD15+ cells and CD38+ cells, compared with the CD14+CD16-
      monocytes. When compared with the CD14dimCD16bright monocytes in PB, those in
      PBPC collections exhibited higher expression of CD4 and lower expression of
      CD11b, and also showed higher percentages of CD4+ cells and CD38+ cells and a
      lower percentage of CD11b+ cells. These results suggest that PBPC collections may
      be rich in the CD14+CD16+ monocytes in which the proportion of the immature
      population is increased. It is likely that these monocytes participate in the
      haematological and immune recovery after PBPC transplantation.

PMID- 10209506
TI  - HLA-DMB expression by thyrocytes: indication of the antigen-processing and
      possible presenting capability of thyroid cells.
AB  - Expression of HLA class II molecules on thyrocytes is a characteristic feature of
      autoimmune thyroid disease and may lead the thyroid cells to present autoantigens
      to CD4+ T lymphocytes. Since HLA-DM is a critical molecule in class II-restricted
      antigen processing and presentation, we assessed the expression of HLA-DMB, 
      invariant chain (Ii), class II transactivator (CIITA) and DRA in an
      untransformed, pure thyrocyte strain HTV-59A. Here we report that both HLA-DMB
      mRNA and the protein are expressed in thyrocytes and that CIITA expression is
      enhanced by interferon-gamma (IFN-gamma) treatment and occurs before DMB, Ii and
      DRA up-regulation, suggesting CIITA expression is a requirement for antigen
      processing in thyrocytes. These results indicate that thyrocytes are capable of
      antigen processing and possibly antigen presentation to T cells.

PMID- 10209507
TI  - Jejuna of patients with insulin-dependent diabetes mellitus (IDDM) show signs of
      immune activation.
AB  - The roles of enteric viruses and food antigens as possible triggers in human
      insulin-dependent diabetes mellitus and the evidence that mucosal-associated
      homing receptors are important in both human and experimental diabetes prompted
      us to undertake an immunohistochemical study of intestinal specimens from
      patients with IDDM. We studied jejunal morphology and immunohistochemistry in 26
      patients with IDDM, 13 of whom had the HLA-DQB1*0201 gene and therefore a higher
      risk of coeliac disease. The findings were compared with those in specimens from
      age-matched controls. Villous structure and the density of the intraepithelial
      lymphocytes were normal in every biopsy specimen. The extent of positivity with
      anti-DR and -DP antibodies in the villous epithelium was significantly greater in
      the specimens from patients than in those from controls (P = 0.0002 in both
      comparisons). The crypts were also more positive: for DR P = 0.0001, and for DP P
      = 0.002. The densities of T cells, CD4+, CD8+, and T cell receptor alpha/beta+
      and gamma/delta+ cells in the epithelium and lamina propria were similar in
      patients and controls, but the patients had significantly more alpha 4/beta 7
      integrin+ cells in the lamina propria (P = 0.006). No difference was seen between
      HLA-DQB1*0201-positive and -negative patients. These findings reflect a stage of
      inflammation in the structurally normal intestines of patients with IDDM and
      suggest secretion of inflammatory Th1-type cytokines in the intestine.

PMID- 10209508
TI  - Disease-associated autoantibodies and HLA-DQB1 genotypes in children with newly
      diagnosed insulin-dependent diabetes mellitus (IDDM). The Childhood Diabetes in
      Finland Study Group.
AB  - The possible relation between HLA-DQ genotypes and both frequencies and levels of
      autoantibodies associated with IDDM was assessed by examining HLA-DQB1 alleles
      and antibodies to islet cells (ICA), insulin (IAA), glutamic acid decarboxylase
      (GADA) and the protein tyrosine phosphatase-related IA-2 molecule (IA-2A) in 631
      newly diagnosed diabetic children under the age of 15 years. ICA were found in
      530 children (84.0%), while close to half of the subjects (n = 307; 48.7%) tested
      positive for IAA. GADA were detected in 461 index cases (73.1%), with a higher
      frequency in those older than 10 years (78.9% versus 69.2% in the younger ones; P
      = 0.006). More than 85% of the children (n = 541; 85.7%) tested positive for IA
      2A. Altogether there were only 11 children (1.7%) who had no detectable
      autoantibodies at diagnosis. There were no differences in the prevalence of ICA
      or GADA between four groups formed according to their HLA-DQB1 genotype
      (DQB1*0302/02, *0302/X (X = other than *02), *02/Y (Y = other than *0302) and
      other DQB1 genotypes). The children with the *0302/X genotype had a higher
      frequency of IA-2A and IAA than those carrying the *02/Y genotype (93.8% versus
      67.3%, P < 0.001; and 49.0% versus 33.6%, P = 0.002, respectively). The children
      with the *02/Y genotype had the highest GADA levels (median 36.2 relative units
      (RU) versus 14.9 RU in those with *0302/X; P = 0.005). Serum levels of IA-2A and
      IAA were increased among subjects carrying the *0302/X genotype (median 76.1 RU
      versus 1.6 RU, P = 0.001; and 50 nU/ml versus 36 nU/ml, P = 0.004) compared with
      those positive for *02/Y. Only three out of 11 subjects homozygous for *02
      (27.3%) tested positive for IA-2A, and they had particularly low IA-2A (median
      0.23 RU versus 47.6 RU in the other subjects; P < 0.001). The distribution of HLA
      DQB1 genotypes among autoantibody-negative children was similar to that in the
      other patients. These results show that DQB1*0302, the most important single IDDM
      susceptibility allele, is associated with a strong antibody response to IA-2 and
      insulin, while GAD-specific humoral autoimmunity is linked to the *02 allele, in
      common with a series of other autoimmune diseases as well as IDDM. We suggest
      that IA-2A may represent beta cell-specific autoimmunity, while GADA may
      represent a propensity to general autoimmunity.

PMID- 10209509
TI  - Functional expression of Fas and Fas ligand on human intestinal intraepithelial
      lymphocytes.
AB  - Intestinal intraepithelial lymphocytes (IEL) constitute the first lymphoid
      compartment to encounter dietary antigens and intestinal pathogens. IEL are
      proposed to be involved in the defence against bacterial and viral invasion and
      to play an important role in mucosal immunity. Fas (CD95/APO-1) is a surface
      receptor that induces apoptotic cell death upon ligation with Fas ligand (FasL).
      The aim of this study was to examine the expression and function of Fas and FasL
      on freshly isolated normal human colonic IEL. The expression and function of Fas
      and FasL on IEL isolated from 40 normal colonic specimens were examined by flow
      cytometry, reverse transcriptase-polymerase chain reaction, immunohistochemistry,
      and DNA-release cytotoxicity assay. Virtually all CD3+ IEL (95.2 +/- 4.3%)
      expressed Fas and were sensitive to agonistic anti-Fas antibody, whereas only
      56.6 +/- 8.4% of peripheral T lymphocytes expressed Fas and were resistant to the
      antibody. We also detected FasL mRNA and protein (40.1 +/- 4.2%) on IEL, and
      found that IEL exerted FasL-mediated cytotoxicity against Fas-expressing target
      cells. These findings suggest that human IEL are activated in situ but are
      tightly regulated by the constitutive expression of functional Fas and FasL to
      maintain homeostasis of the mucosal immune system.

PMID- 10209510
TI  - Rapid intestinal ischaemia-reperfusion injury is suppressed in genetically mast
      cell-deficient Ws/Ws rats.
AB  - Ws/Ws rats have a small deletion of the c-kit gene, and are deficient in both
      mucosal and connective tissue-type mast cells. In this study, the role of mucosal
      type mast cells (MMC) in the development of intestinal ischaemia-reperfusion
      injury was investigated in Ws/Ws rats. Autoperfused segments of the jejunum were
      exposed to 60 min of ischaemia, followed by reperfusion for various time periods.
      The epithelial permeability was then assessed by the 51Cr-EDTA clearance rate. In
      the control (+/+) rats, the maximal increase in mucosal permeability was achieved
      at 45 min of reperfusion. In contrast, this increase was significantly and
      potently attenuated in the Ws/Ws rats. Mucosal alkaline phosphatase activity
      decreased in the control (+/+) rats, but was not altered in the Ws/Ws rats. There
      were no differences in mucosal myeloperoxidase activity, indicating that
      granulocytes did not contribute to tissue injury. These results provide direct
      evidence for the role of mast cells in the pathogenesis of intestinal ischaemia
      reperfusion injury.

PMID- 10209511
TI  - Apoptosis of Mycobacterium avium-infected macrophages is mediated by both tumour
      necrosis factor (TNF) and Fas, and involves the activation of caspases.
AB  - Mycobacterium avium causes disseminated infection in AIDS patients and several
      forms of infection in immunocompetent hosts. Recent studies have shown that M.
      avium infection of macrophages in vitro leads to apoptosis of significant numbers
      of infected cells. Several strains of M. avium used to infect human macrophages
      for 5 days (multiplicity of infection of 10) triggered 28-46% higher levels of
      apoptosis than observed with uninfected macrophages at the same time points.
      Mycobacterium avium strains unable to replicate intracellularly (rep-) resulted
      in a 15% rate of apoptosis, while M. smegmatis-infected monolayers showed the
      same percentage of apoptotic cells as the uninfected macrophage control. The
      presence of anti-TNF-alpha antibody reduced apoptosis to 17% and the presence of
      anti-Fas antibody reduced apoptosis to 10%. When both antibodies were used
      together, the apoptosis level was 5% above the control. Treatment with TGF-beta
      also reduced the number of apoptotic cells in infected monolayers. If
      intracellular growth was inhibited, apoptosis of macrophages decreased
      significantly. It was also shown that apoptosis was associated with IL-1 beta
      converting enzyme (ICE) activation and was significantly reduced by a caspase
      inhibitor. Gaining understanding of the mechanisms of M. avium-associated
      apoptosis of macrophages will provide important insight into M. avium
      pathogenesis.

PMID- 10209512
TI  - Superantigen-induced T cell responses in acute rheumatic fever and chronic
      rheumatic heart disease patients.
AB  - CD4+ and CD8+ T cells from healthy donors, acute rheumatic fever (ARF) and
      chronic rheumatic heart disease (CRHD) patients responded variably to a
      superantigen from Streptococcus pyogenes--Streptococcal pyrogenic erythrogenic
      toxin A (SPE-A). In vitro culture of CD4+ T cells from ARF patients (CD4-ARF)
      with SPE-A exhibited a Th1 type of response as they produced high levels of IL-2,
      while CD4+ T cells from CRHD patients (CD4-RHD) secreted IL-4 and IL-10 in large
      amounts, i.e. Th2 type of cytokine profile. The skewing of human CD4+ T cells (in
      response to SPE-A stimulation) to Th1 or Th2 type reflects the role of the two
      subsets in a disorder with differing intensities at the two extremes of the
      spectrum. Moreover, the anergy induction experiments revealed that CD8-ARF and
      CD8-RHD undergo anergy (to different extents), whereas CD4+ T cells do not, in
      response to re-stimulation by SPE-A. These results initially demonstrate that
      both CD4+ and CD8+ T cells respond differentially to SPE-A, and hence it is an
      important observation with respect to the pathogenesis of ARF/CRHD. Anergy in
      CD8+ T cells in the presence of SPE-A in vitro goes a step further to show the
      clinical relevance of these cells and their possible role in suppression of the
      disease.

PMID- 10209513
TI  - An IgG1 titre to the F1 and V antigens correlates with protection against plague
      in the mouse model.
AB  - The objective of this study was to identify an immunological correlate of
      protection for a two-component subunit vaccine for plague, using a mouse model.
      The components of the vaccine are the F1 and V antigens of the plague-causing
      organism, Yersinia pestis, which are coadsorbed to alhydrogel and administered
      intramuscularly. The optimum molar ratio of the subunits was determined by
      keeping the dose-level of either subunit constant whilst varying the other and
      observing the effect on specific antibody titre. A two-fold molar excess of F1 to
      V, achieved by immunizing with 10 micrograms of each antigen, resulted in optimum
      antibody titres. The dose of vaccine required to protect against an upper and
      lower subcutaneous challenge with Y. pestis was determined by administering doses
      in the range 10 micrograms F1 + 10 micrograms V to 0.01 microgram F1 + 0.01
      microgram V in a two-dose regimen. For animals immunized at the 1-microgram dose
      level or higher with F1 + V, an increase in specific IgG1 titre was observed over
      the 8 months post-boost and they were fully protected against a subcutaneous
      challenge with 10(5) colony-forming units (CFU) virulent Y. pestis at this time
      point. However, immunization with 5 micrograms or more of each subunit was
      required to achieve protection against challenge with 10(7) CFU Y. pestis. A new
      finding of this study is that the combined titre of the IgG1 subclass, developed
      to F1 plus V, correlated significantly (P < 0.05) with protection. The titres of
      IgG1 in vaccinated mice which correlated with 90%, 50% and 10% protection have
      been determined and provide a useful model to predict vaccine efficacy in man.

PMID- 10209514
TI  - IL-10 in HIV infection: increasing serum IL-10 levels with disease progression-
      down-regulatory effect of potent anti-retroviral therapy.
AB  - To examine the potential pathogenic role of IL-10 in HIV infection, we measured
      serum IL-10 levels in 51 HIV-infected patients and 23 healthy controls both on
      cross-sectional and longitudinal testing. All clinical groups (Centers for
      Disease Control (CDC) categories) of HIV-infected patients had significantly
      higher circulating IL-10 levels than controls, with the highest levels among the
      AIDS patients, particularly in patients with ongoing Mycobacterium avium complex
      (MAC) infection. Among 32 HIV-infected patients followed with longitudinal
      testing (median observation time 39 months), patients with disease progression
      had increasing IL-10 levels in serum, in contrast to non-progressing patients
      where levels were stable. While both IL-10 and tumour necrosis factor-alpha (TNF
      alpha) increased in patients with disease progression, the IL-10/TNF-alpha ratio
      decreased in these patients, suggesting imbalance between these two cytokines.
      Finally, we found that highly active anti-retroviral therapy (HAART) induced a
      significant, gradual decrease in IL-10 levels but without normalization. These
      findings suggest a pathogenic role for IL-10 in HIV infection, and may suggest a
      possible role for immunomodulating therapy which down-regulates IL-10 activity in
      addition to concomitant potent anti-retroviral therapy in HIV-infected patients.

PMID- 10209515
TI  - A mathematical model predicting anti-hepatitis B virus surface antigen (HBs)
      decay after vaccination against hepatitis B.
AB  - The determination of serum levels of antibodies against hepatitis B virus surface
      antigen (anti-HBs) after hepatitis B vaccination is currently the only simple
      test available to predict the decay of protection and to plan the administration
      of booster doses. A total of 3085 vaccine recipients of plasma-derived and
      recombinant vaccine have been followed for 10 years to determine the kinetics of
      anti-HBs production and to construct a mathematical model which could efficiently
      predict the anti-HBs level decline. The anti-HBs peak level was reached 68 days
      after the last dose of recombinant vaccine and 138 days after the last dose of
      plasma-derived vaccines. The age of vaccinees negatively influenced the anti-HBs
      levels and also the time necessary to reach the anti-HBs peak. A bilogarithmic
      mathematical model (log10 level, log10 time) of anti-HBs decay has been
      constructed on a sample of recombinant vaccine recipients and subsequently
      validated on different samples of recombinant or plasma-derived vaccine
      recipients. Age, gender, type of vaccine (recombinant or plasma-derived), number
      of vaccine doses (three or four) did not influence the mathematical model of
      antibody decay. The program can be downloaded at the site:
      http:@www2.stat.unibo.it/palareti/vaccine.htm . Introducing an anti-HBs
      determination obtained after the peak, the program calculates a prediction of
      individual anti-HBs decline and allows planning of an efficient booster policy.

PMID- 10209516
TI  - Leishmanin skin test lymphoproliferative responses and cytokine production after
      symptomatic or asymptomatic Leishmania major infection in Tunisia.
AB  - Resistance to Leishmania parasite infection requires the development of a
      cellular immune response that activates macrophage leishmanicidal activity. In
      this study we have investigated the lymphoproliferative responses and in vitro
      cytokine production of peripheral blood mononuclear cells (PBMC) from individuals
      living in an endemic area for L. major infection in Tunisia. The results were
      compared with the DTH reaction of the leishmanin skin test (LST). Sixty-seven
      individuals were included in the study: 22 persons (age range 9-60 years) who
      developed, 2 years before the present study, a parasitologically confirmed
      localized cutaneous leishmaniasis (LCL) that healed spontaneously, and 45
      individuals (age range 18-20 years) born and living in the same area, with no
      previous history of LCL. LST was positive (skin induration > or = 5 mm) in 20/22
      cured cases of LCL and in 75% of healthy individuals without history of LCL. LST+
      individuals expressed vigorous Leishmania-specific lymphoproliferative responses
      associated with in vitro production of interferon-gamma (IFN-gamma) but not IL-4.
      Interestingly, IL-10 was detected in parallel with the highest levels of IFN
      gamma in PBMC supernatants from 3/20 cured LCL and 8/25 individuals without
      history of LCL. Our results showed a 98% concordance between the DTH reaction
      assessed by LST and the in vitro proliferative assay induced by soluble
      leishmanial antigens. Moreover, proliferative assays as well as cytokine analysis
      did not show any significant difference of the immune memory to parasite antigens
      developed by patients who had overt cutaneous leishmaniasis and those who had
      apparently asymptomatic infection.

PMID- 10209517
TI  - T cell responses to the putative dominant autoepitope in primary biliary
      cirrhosis (PBC).
AB  - PBC is characterized by T cell-mediated destruction of the biliary epithelial
      cells lining the small intrahepatic bile ducts. The E2 and E3 binding protein
      (E3BP (protein X)) components of pyruvate dehydrogenase complex (PDC) are disease
      specific autoantigens in PBC. Attempts to localize the T cell autoepitopes within
      PDC-E2 have, however, generated contradictory results. One study has suggested
      the presence of T cell epitopes throughout PDC-E2, whilst another has identified
      a single dominant 14 amino acid T cell epitope (p163) spanning the lipoic acid
      binding lysine residue in the inner lipoyl domain (ILD) of PDC-E2. The aim of the
      current study was to determine the prevalence of T cell responses to p163 and PDC
      E2 ILD, and the role played by lipoylation of these antigens in their
      immunogenicity, in a UK PBC population. We found that the majority of the PBC
      patients showing a 6-day peripheral blood T cell proliferative response to native
      human PDC also responded, in a MHC class II-restricted fashion, to biochemically
      purified PDC-E2 and E3BP (which co-purify) (9/10 positive (SI > 2.76), mean SI
      5.74 +/- 5.04 (PDC-E2/E3BP) versus 6.67 +/- 3.84 (PDC), P = NS), implying that
      the important PBC-specific T cell epitopes are contained within the PDC-E2 or
      E3BP components of PDC. Only a minority of patients responsive to PDC, however,
      responded to either lipoylated recombinant PDC-E2 ILD (4/10 positive, mean SI
      1.98 +/- 1.24, P < 0.005 versus PDC response) or lipoylated p163 (4/12 positive,
      mean SI 1.90 +/- 1.58, P < 0.001). The lipoylation state did not affect the T
      cell response to either ILD or p163. Our findings suggest that in some UK
      patients with PBC there are immunodominant T cell autoepitopes within PDC-E2/E3BP
      which are outside the ILD of PDC-E2.

PMID- 10209518
TI  - Increased bcl-2 expression in lymphocytes and its association with hepatocellular
      damage in patients with autoimmune hepatitis.
AB  - The proto-oncogene product bcl-2 is known to inhibit apoptotic cell death, and
      its dysregulation might play a critical role in the development of autoimmune
      disease. To elucidate the role of bcl-2 in autoimmune hepatitis (AIH), its
      expression in peripheral blood mononuclear cells (PBMC) and in liver-infiltrating
      lymphocytes (LIL) was investigated. Increased bcl-2 expression in PBMC was found
      in AIH patients compared with that in chronic hepatitis C (CHC) patients and in
      healthy controls. The level of bcl-2 expression significantly correlated with
      serum ALT level. Further analysis showed that CD4+ T cells are enriched in bcl-2
      expressing PBMC. To characterize the Th1/Th2 profile of bcl-2-expressing CD4+ T
      cells, intracellular interferon-gamma (IFN-gamma) and IL-4 were analysed. The
      results revealed that most of the bcl-2-expressing cells were found to be IFN
      gamma-secreting Th1 cells. In three patients for whom their clinical courses
      could be followed, bcl-2 expression was decreased after the initiation of
      immunosuppressive therapy with corticosteroids. However, the level of IFN-gamma +
      cells was not altered. Immunohistochemical analysis also showed that large
      amounts of bcl-2+ cells were observed in periportal area in the liver. In
      conclusion, bcl-2-expressing cells were shown to be increased in peripheral blood
      and liver in AIH and the bcl-2 product was expressed mainly in CD4+ Th1-type
      cells, suggesting that these cells might promote the cellular immune response and
      contribute to the development of hepatitis and hepatocellular damage in AIH.

PMID- 10209519
TI  - Detection of antibodies directed against the cytoplasmic region of the human
      acetylcholine receptor in sera from myasthenia gravis patients.
AB  - The nicotinic acetylcholine receptor (AChR) is the autoantigen in the human
      autoimmune disease myasthenia gravis (MG). Anti-AChR antibodies in MG sera bind
      mainly to conformational epitopes, therefore the determination of their
      specificities requires the use of native AChR. Antibody competition studies
      suggest that most MG antibodies are directed against the extracellular part of
      the molecule, whereas antibodies directed against the cytoplasmic region of the
      AChR have not been detected. To determine whether even small quantities of such
      antibodies exist in MG sera, we performed competition experiments based on the
      inhibition by MG sera of the binding of MoAbs to the human AChR, rather than
      inhibition by MoAbs of the binding of MG sera performed earlier. When MoAbs
      directed against cytoplasmic epitopes on the alpha or beta subunits (alpha 373
      380 and beta 354-360) were used as test MoAbs, 17% or 9% of MG sera inhibited the
      binding of the anti-alpha or anti-beta subunit MoAbs, respectively, by > or =
      50%. Non-specific inhibition was excluded. These results suggest the presence, in
      several MG sera, of antibodies directed against cytoplasmic regions of the AChR;
      yet these antibodies seemed to represent a relatively small proportion of the
      total anti-AChR antibodies. The corresponding epitopes may be involved in the
      inducing mechanisms in certain MG cases, and knowledge of the presence of such
      antibodies may be useful in understanding the autoimmune mechanism involved in
      MG.

PMID- 10209520
TI  - Mice with early onset of death (EOD) due to lupus glomerulonephritis.
AB  - Both MRL-lpr/lpr (lpr) and BXSB mice fall victim to autoimmune disease as a
      function of age. To combine their properties, brother-sister mating of (female
      lpr x male BXSB)F1 mice was done. Mice for mating were selected according to
      indicators of early onset of glomerulonephritis and subsequent early death (i.e.,
      EOD). This mating was continued for more than 16 generations. The EOD mice thus
      established had homozygous H-2k/k, lpr/lpr, and possible yaa/- (in the case of
      males). The average life span of males was 83 days while that of females was 126
      days. After 12 weeks of age, the majority (> 80%) of male EOD mice were
      characterized by the abnormality of urine due to glomerulonephritis. We then
      characterized how glomerulonephritis was evoked, especially in terms of expanding
      lymphocyte subsets in various immune organs. Similar to the case of parental lpr
      mice, the major expanding cells were CD4-8-B220+ TCRint cells in the immune
      organs and kidney. In addition, myeloid cells were found to infiltrate the
      kidney. This massive infiltration of both TCRint cells and myeloid cells might be
      responsible for the onset of acute glomerulonephritis. Even after more than 50
      generations, these EOD mice still carry both lpr and yaa genes. These results
      suggest that EOD mice might be a very useful tool for the study of acute lupus
      glomerulonephritis which is evoked by the genetic abnormalities.

PMID- 10209521
TI  - Increased interferon-gamma (IFN-gamma) levels produced in vitro by alloactivated
      T lymphocytes in systemic sclerosis and Raynaud's phenomenon.
AB  - The aim of the present study was to analyse the in vitro proliferation and
      cytokine production by alloantigen-stimulated peripheral blood mononuclear cells
      (PBMC) obtained from patients affected by systemic sclerosis (SSc) and patients
      with Raynaud's phenomenon (RP). In SSc patients the proliferation of PBMC
      stimulated in vitro with alloantigens was significantly increased compared with
      healthy subjects, while no differences were observed for RP patients. Lymphocytes
      from SSc patients also produced larger amounts of IFN-gamma compared with healthy
      controls. However, patients with clinically active disease had lower IFN-gamma
      levels than those found in clinically stable patients. Patients affected by RP
      showed significantly higher levels of IFN-gamma than healthy subjects. Analysis
      at the clonal level of the lymphocyte subsets involved in alloantigen stimulation
      in one patient affected by active SSc, and one subject with RP confirmed the
      results obtained using PBMC. In particular, in the RP patient but not in the SSc
      patient, we observed a population of CD4+ T cells which proliferated to
      alloantigens in vitro and produced high levels of IFN-gamma. We suggest that T
      lymphocytes producing high levels of IFN-gamma might play a protective role in RP
      patients and in established scleroderma.

PMID- 10209522
TI  - Levels of IL-12 in the sera of patients with systemic lupus erythematosus (SLE)-
      relation to Th1- and Th2-derived cytokines.
AB  - IL-12 is a cytokine that induces Th1-derived cytokines (interferon-gamma (IFN
      gamma) and IL-2). The significance of IL-12 in human autoimmunity is no clear,
      and the serum levels of IL-12 in SLE are not clearly established. Therefore, we
      examined the levels of IL-12 in 39 patients with active SLE, with sandwich ELISA.
      The levels of IL-12 in patients were significantly higher than in normal
      subjects. Patients with high levels of IL-12 also had high levels of IFN-gamma,
      while their levels of IL-13 were significantly lower than in patients with normal
      levels of IL-12. Patients with pulmonary involvement had high levels of IL-12,
      and steroid therapy decreased the IL-12 level in three patients. In a
      retrospective study of seven patients, various changes of IL-12 and IL-13 were
      recognized before disease flare. Thus, in SLE patients, the level of IL-12 was
      increased and this increase was related to the change of Th1- or Th2-derived
      cytokines with some organ involvement.

PMID- 10209523
TI  - Up-regulation of intercellular adhesion molecule-1 (ICAM-1), endothelial
      leucocyte adhesion molecule-1 (ELAM-1) and class II MHC molecules on pulmonary
      artery endothelial cells by antibodies against U1-ribonucleoprotein.
AB  - In order to elucidate the pathogenic role(s) of autoantibodies in connective
      tissue disease (CTD), we examined whether autoantibodies against U1
      ribonucleoprotein (RNP) and double-stranded (ds) DNA can up-regulate ICAM-1, ELAM
      1 and class I and II MHC molecule expression on pulmonary artery endothelial
      cells (HPAEC). ICAM-1, ELAM-1 and class II MHC molecule expression on HPAEC
      cultured in the presence of anti-U1-RNP-containing and anti-dsDNA-containing IgG
      from CTD patients was up-regulated significantly in comparison with that on HPAEC
      cultured with IgG from normal healthy volunteers. Affinity chromatographic
      enrichment and depletion of the anti-U1-RNP antibody content of anti-U1-RNP
      containing IgG confirmed that the anti-U1-RNP antibody did up-regulate ICAM-1,
      ELAM-1 and class II MHC molecule expression. The finding that an IgG F(ab')2
      purified anti-U1-RNP antibody also up-regulated expression of these molecules may
      indicate that mechanisms other than Fc receptor-mediated stimulation are
      involved. These in vitro findings suggest that autoantibodies against U1-RNP and
      dsDNA play important roles in the immunopathological processes leading to the
      proliferative pulmonary arterial vasculopathy observed in CTD patients with
      pulmonary hypertension by up-regulating adhesion and class II MHC molecule
      expression on endothelial cells.

PMID- 10209524
TI  - Active suppression in orally tolerized rats coincides with in situ transforming
      growth factor-beta (TGF-beta) expression in the draining lymph nodes.
AB  - Adult rats were fed pellets containing ovalbumin (OvA) during 4 weeks, and were 2
      weeks thereafter immunized subcutaneously with a mixture of OvA and human serum
      albumin (HSA) in Freund's complete adjuvant (day 0). As a result of the
      immunization, the draining lymph nodes of the nontolerized (control) rats were
      heavily enlarged from day 10 to day 18; however, this size increase was absent in
      the OvA-fed rats. This manifestation of active suppression in the tolerized rats
      was preceded by the appearance of scattered CD4+ TGF-beta-expressing T cells in
      the T cell area of their lymph nodes (days 5-8); correspondingly, the levels of
      TGF-beta mRNA in the nodes were elevated in the tolerant rats compared with the
      control rats. The anti-OvA antibody levels in sera from the rats revealed that
      there was an initial B cell priming in the OvA-fed group, with levels higher than
      in the control group during the first week. Thereafter, suppression governed the
      response, and from day 10 onwards the anti-OvA levels were considerably lower
      than in the controls. When other groups of animals were pretreated with
      neutralizing anti-TGF-beta antibodies 1 day before the immunization, the anti-OvA
      response of the OvA-fed rats was restored to the levels of the control group,
      demonstrating the importance of TGF-beta in the maintenance of suppression. In
      conclusion, we demonstrate that TGF-beta-producing cells appear in the draining
      lymph nodes shortly after immunization in rats made orally tolerant using a
      relatively high-dose feeding regime; these cells are probably responsible for the
      down-regulation of the immune response observed in the OvA-fed rats.

PMID- 10209526
TI  - [HIV research: the interim report from Chicago].

PMID- 10209525
TI  - The effects of extracorporeal whole body hyperthermia on the functional and
      phenotypic features of canine peripheral blood mononuclear cells (PBMC).
AB  - In this study the effect of transient 42.3 degrees C whole body hyperthermia
      (WBH) on the distribution of PBMC phenotypes and in vitro blastogenic
      responsiveness was determined in dogs. Hyperthermia (n = 6) was induced by
      heating venous blood during extracorporeal circulation (venous perfusion WBH);
      perfused non-heated dogs (n = 4) were used as controls. Both euthermic and
      hyperthermic perfusion produced transient lymphopenia which normalized in
      controls after perfusion but persisted in hyperthermic animals throughout the 8
      day post-perfusion observation interval. The transient lymphopenia in control
      dogs was non-selective. In contrast, WBH-associated lymphopenia was selective, in
      that CD5+ T lymphocytes were more sensitive to hyperthermia than sIg+ B cells
      and, within the T cell compartment, suppressor (CD8+) cells were more sensitive
      to hyperthermic stress than helper (CD4+) lymphocytes. Functional analyses showed
      that WBH caused persistent suppression of PBMC blastogenesis in response to T
      cell phytomitogens. Increased plasma cortisol levels were correlated to peak
      lymphopenia and hyporesponsiveness to phytomitogens. Despite these alterations,
      high grade WBH was well tolerated and there was no evidence of opportunistic
      infection.

PMID- 10209528
TI  - [Intermittent therapy ought to strengthen the immune system].

PMID- 10209529
TI  - [Latent infection in exposed high-risk persons].

PMID- 10209530
TI  - [AIDS research benefits patients with hepatitis C].

PMID- 10209531
TI  - [Experiences with temporary vena cava filters in 114 at-risk patients with
      thrombosis or thromboembolism].
AB  - BACKGROUND AND OBJECTIVES: The indications for temporary implantation of a vena
      cava filter remain unclear and there are as yet few data about its complications
      and reliability. It was the aim of this study to determine the efficacy and
      complication rate of the temporary use of a vena cava filter (VCF) in a large
      group of patients at high risk of pulmonary embolism, and thus contribute to
      defining the indications for such temporary implantation. PATIENTS AND METHODS:
      Between November 1991 and October 1997 a total of 118 VCF were implanted in four
      groups of a total of 114 patients (67 women, 47 men; average age 45.3 +/- 19.8
      [12-82] years) to prevent pulmonary embolism: those (1) with massive or fulminant
      pulmonary embolism (n = 54); (2) with mechanical thrombus fragmentation and (or)
      local catheter-delivered systemic thrombolysis in pelvic, leg or caval vein
      thrombosis (n = 42); (3) with systemic thrombolysis in case of floating thrombi
      at the femoral, iliac or caval veins (n = 7); and (4) as perioperative measure in
      caesarean section, venous thrombectomy, other surgical interventions or when
      anticoagulation had to be discontinued in patients with deep vein thrombosis (n =
      11). RESULTS: Filters remained implanted for a mean of 6.1 +/- 3.4 (1-16) days.
      Placement had to be corrected because of filter dislocation in eight patients.
      Proven pulmonary embolism occurred after filter implantation in only one patient,
      after filter displacement into the unthrombosed contralateral iliac vein.
      Thrombus deposition on the filter before its removal was demonstrated in nine
      patients: thrombolysis was effective in seven of them, while thrombosed filters
      had to be removed surgically in two. Residual thrombi were found on the filter in
      six further patients. No pulmonary embolism occurred in connection with filter
      removal. Local complications at or around the site of insertion of the
      introducing catheter occurred in 53 of the 114 patients (46.5%): haematoma in 42,
      infection in 21 and brachial vein thrombosis in three patients. CONCLUSIONS: The
      rate of clinically relevant pulmonary embolism can probably be reduced to a
      minimum by the implantation of a temporary vena cava filter. The overall
      complication rate is high, but serious complications are rare.

PMID- 10209532
TI  - [Adult progeria (Werner's syndrome)].
AB  - HISTORY: A 48-year-old man was referred with progressive claudication and
      nocturnal pain at rest in the right foot. During the last few years exercise
      induced pain, ulcerations and necroses had developed in both legs without any
      evidence of relevant macroangiopathies. The patient showed marked morphological
      changes. He had bilateral cataracts since aged 35 years. At 40 years he had
      undergone a transurethral resection of a bladder carcinoma. One of his brothers
      showed similar morphological changes, but they were absent in his parents and
      three siblings. INVESTIGATIONS: Radiology of the right foot revealed extensive
      para-osseous soft-tissue calcifications. Direct right femoral angiography
      demonstrated distal occlusions of the anterior and posterior tibial arteries as
      well as subtotal occlusion of the fibular artery. Routine laboratory tests were
      normal, as were all measured antibody titres. TREATMENT AND COURSE: The
      peripheral vascular disease, stage IV, of the right leg were presumably caused by
      adult progeria (Werner's syndrome). Percutaneous transluminal angioplasty (PTAP)
      of the distal fibular and, later, of the posterior tibial artery was performed,
      and prostacyclins, antibiotics and platelet-aggregation inhibitors were
      administered. Although the PTAP was technically successful, the state of the
      right foot remained critical, due to the existing microangiopathy and the
      impaired proliferation and healing capacity of the tissues as part of the adult
      progeria. CONCLUSIONS: The diagnosis of adult progeria is usually made because of
      the patients' characteristic morphology and typical concomitant diseases. The
      average age of patients at diagnosis is 37 years. The syndrome is caused by a
      helicase defect. This enzyme group unwinds double-helix RNA and DNA. Because the
      syndrome is rare and gene analysis is complex, it is unlikely that a commercial
      screening test will become available.

PMID- 10209534
TI  - [Physiotherapeutic possibilities in the treatment of postpolio syndrome].

PMID- 10209533
TI  - [Recurrent subacute encephalopathy in the framework of idiopathic
      hypereosinophilic syndrome].
AB  - HISTORY: An 81-year-old man, previously good health, suddenly developed confusion
      and rapidly progressive severe tetraparesis. INVESTIGATIONS: Peripheral blood and
      bone marrow revealed marked eosinophilia: allergic, parasitic, neoplastic or
      vasculitic causes were excluded. Magnetic resonance imaging demonstrated multiple
      lesions in the cortical and subcortical white matter. DIAGNOSIS, TREATMENT AND
      COURSE: The findings indicated idiopathic hypereosinophilic syndrome involving
      the central nervous system and treatment with high doses of glucocorticoids was
      started. After a stormy course almost complete recovery occurred. CONCLUSION:
      Idiopathic hypereosinophilic syndrome can rarely manifest itself a an isolated
      severe subacute encephalopathy.

PMID- 10209535
TI  - [Contrast medium induced nephropathy: pathogenesis, clinical aspects,
      prevention].

PMID- 10209536
TI  - [Identification procedure following the law on severely handicapped. The route
      from the application to the decision].

PMID- 10209537
TI  - [Autoimmune hemolytic anemia caused by interferon?].

PMID- 10209538
TI  - [Impact of an information campaign on cardiovascular risk factors. 5-year results
      at the study town Epernon].
AB  - OBJECTIVES: Information campaigns are implemented to improve knowledge of
      cardiovascular disease and risk factors. The impact of these programs must be
      evaluated to determine whether they truly contribute to modifying risk factors in
      the population. METHODS: A 5-year information campaign on cardiovascular disease
      and risk factors was conducted in Epernon, France. The main objectives of the
      campaign focused on stopping smoking, regular physical exercise and balanced
      nutrition. Data were collected from a representative sample of the female and
      male population aged 20 to 65 years selected from the study town Epernon (500
      subjects), and in control towns, Magny-en-Vexin and Moret-sur-Loing (200
      subjects). The study town and control towns were comparable for population,
      demographic characteristics and geographic localization (distance from Paris).
      The subjects were invited to respond to a questionnaire on demographic data,
      attitudes toward health, risk factors and diet and underwent a clinical
      examination with blood tests. RESULTS: The initial sample included 961 subjects
      and 68.5% participated in the final survey. We were unable to evidence any
      significant difference in risk factors or the 10-year risk score calculated from
      the Framingham equation adapted to France. The information campaign was well
      accepted, the population not expression a feeling of lassitude. The campaign had
      a minimal effect on the way individuals relate to health. There was a fall in
      mean energy intake, mainly fat calories, which was similar in all three towns.
      CONCLUSION: No major modification in cardiovascular risk factors was observed in
      this low-risk population, suggesting that future information campaigns should be
      aimed at targeted populations with a higher risk profile using simple and
      selected messages.

PMID- 10209539
TI  - [Spinocerebellar ataxia and polyneuropathy secondary to vitamin E deficiency].
AB  - BACKGROUND: Cerebellar ataxia or peripheral neuropathy can be signs of vitamin E
      deficiency. We report two cases. CASE REPORTS: Two patients developed vitamin E
      deficiency subsequent to intestinal malabsorption. The first patient had a
      duodenogastric communication and dilatation of the first jejunal loop. The second
      patient had deficient pancreas secretion and dilatation of the biliary tree.
      DISCUSSION: Vitamin E deficiency is generally secondary to acquired or hereditary
      malabsorption syndrome. It can also occur in the absence of malabsorption by
      hereditary deficiency in alpha-tocopherol transporter. Vitamin E supplements are
      required for malabsorption. The etiology work-up of neuropathy or cerebellar
      ataxia should include vitamin E assay.

PMID- 10209540
TI  - [A rare cause of sudden death in young adults with "normal" heart: the Brugada
      syndrome].
AB  - BACKGROUND: Brugada syndrome is a rare condition causing sudden death in young
      adults due to unexpected sudden-onset ventricular fibrillation. Diagnosis is
      based on the presence of an ST depression in the anteroseptal territory and a
      right branch block. No underlying dysrhythmic condition or arrhythmogenic heart
      disease can be detected. CASE REPORT: A 15-year old boy with an uneventful past
      history experienced cardiocirculatory failure due to ventricular fibrillation
      during a sports competition. Cardiac arrest developed and resuscitation was
      initially successful but death ensued due to cerebral anoxia. Characteristic
      electrocardiographic signs and the presence of similar anomalies in a brother and
      an aunt led to the diagnosis of Brugada syndrome. DISCUSSION: Brugada syndrome is
      a recently discovered hereditary condition with a probably underestimated
      prevalence. Systematic family studies have demonstrated autosomal dominant
      inheritance. The characteristic electrocardiographic anomalies can be transitory
      and may be unmasked by sensitivization tests. The only currently effective
      treatment is the implantable defibrillator programmed to prevent sudden death by
      ventricular fibrillation.

PMID- 10209541
TI  - [Unusual skin reaction after intravenous infusion of polyvalent immunoglobulins:
      3 case reports].

PMID- 10209542
TI  - [Tuberculous osteoarthritis revealed by ankle injury].

PMID- 10209543
TI  - [Association of celiac disease and lupus].

PMID- 10209544
TI  - [What treatment for the common cold?].

PMID- 10209546
TI  - [Palliative care: an interview with Dr. J.M. Gomas].

PMID- 10209545
TI  - [Generic drugs and the rights of substitution].
AB  - Compared with other countries with a similar socio-economic environment, generic
      drugs account for a very small proportion of pharmaceutical sales in France. The
      recently promulgated law on financing the national healthcare system states that
      drug dispensers have the right to substitute generic drugs for prescription drugs
      in accordance with the drug equivalence repertoire established by the national
      drug agency. How patients, pharmacists, physicians and industrial firms will
      react to this new situation is an open question as use of generic drugs is
      basically unknown in France. Prescribing physicians, members of the drug agency,
      pharmacists, health economists, and insurance company and pharmaceutical firm
      representatives participated in a round table discussion to clarify the ongoing
      debate on the effect of this new cultural situation which calls an end to the
      French "exception" in drug consumption. The concept of generics and their use in
      substitution for prescription drugs was discussed in light of the outlined
      economic objectives together with the advantages and disadvantages patients and
      physicians can expect.

PMID- 10209547
TI  - [Systemic antibiotic therapy in everyday practice: ENT and lower respiratory
      tract infections. Guidelines by the French Drug Agency].

PMID- 10209548
TI  - [Bone and hormones. Effects of parathyroid hormone on the bone].
AB  - ACTION OF PTH: Parathyroid hormone (PTH) stimulates both bone formation and bone
      resorption. It also stimulates synthesis of 1,25-dihydroxyvitamin D3 which
      increases intestinal absorption of calcium and phosphorus and stimulates bone
      resorption. In bone tissue, PTH acts mainly on osteoblasts which, unlike
      osteoclasts, carry PTH receptors. PTH also exerts an indirect action on
      osteoclasts, increasing their number and activity. IMPACT OF INSUFFICIENT PTH: In
      the absence of PTH, bone remodeling is greatly reduced. Increased bone density
      has been observed in patients with hypoparathyroidism studied 10 years after
      total thyroidectomy. IMPACT OF EXCESS PTH: Chronic excess of PTH accelerates bone
      loss. In primary hyperparathyroidism, reduction of bone density to the order of
      10% has been observed, which corresponds to one standard deviation compared with
      normal subjects of the same age and sex. The hypothesis of an increased risk of
      fractures remains unresolved. ADMINISTRATION OF PTH: Intermittent rather than
      continuous subcutaneous administration appears to be necessary to observe the
      anabolic effects of PTH on bone. The conjunction of favorable anabolic effects
      demonstrated in animal models, concerning both bone density and mechanical
      properties, and early studies in humans, provide converging arguments similar to
      those observed in preclinical investigations, suggest that PTH could be a
      promising treatment for osteoporosis.

PMID- 10209549
TI  - [Bone and hormones. Estrogens and antiestrogens: action on osteoporosis].
AB  - ESTROGEN INSUFFICIENCY: Estrogens play a cardinal role in bone tissue in women.
      Estrogen insufficiency leads to accelerated bone loss within 5 to 8 years after
      menopause. HORMONE SUBSTITUTION THERAPY: Substitution therapy prevents
      postmenopausic bone loss (lumbar vertebrae, hip, radius) and reduces the risk of
      osteoporotic fracture. Cohort studies have demonstrated that women given hormone
      substitution therapy for at least 7 years have a significantly higher bone
      density than untreated women. Although still controversial, it would appear that
      the risk of breast cancer increases with prolonged use of hormone substitution
      therapy. SERM: Observations in patients given tamoxifen, an antiestrogen used in
      the treatment of breast cancer, have led to the concept of selective estrogen
      receptor modulators (SERM), a new class of compounds with estrogen agonistic or
      antagonistic activity, depending on the tissue. Among these molecules, raloxifen
      has reached advanced clinical testing phases. Phase III trials have demonstrated
      that raloxifen can prevent bone loss and reduce the risk of vertebral fractures
      while reducing total cholesterol and LDL-cholesterol in menopaused women without
      stimulating the endometrium. SERMs are a promising alternative to hormone
      substitution therapy for the treatment of menopaused women.

PMID- 10209550
TI  - [Bone and hormones. Effects of growth hormone on bone tissue in adults].
AB  - GROWTH HORMONE INSUFFICIENCY: Bone mass is reduced and bone remodeling diminished
      in case of growth hormone insufficiency. ACROMEGALY: In acromegaly, cortical bone
      mass increases due to excessive growth hormone. The effect on trabecular bone is
      less well established. ON THE CELLULAR LEVEL: Growth hormone stimulates the bone
      formation action of osteoblasts and their synthesis of insulin-like growth factor
      I. EFFECTS OF TREATMENT: Contradictory results have been obtained in adults
      treated with growth hormone for insufficiency. Generally, markers of bone
      remodeling are increased, but the effect on bone density is less clear. Long-term
      studies are needed. EFFICACY OF GROWTH HORMONE TREATMENT ON OSTEOPOROSIS: Growth
      hormone has been found to have an effect. Several randomized trials have
      demonstrated moderate increases in bone density.

PMID- 10209551
TI  - [How to fight agaisnt bacterial resistance in the intensive care unit].

PMID- 10209552
TI  - [Ultrasonography during the 1st trimester of pregnancy: optimal contribution
      between the 12th and 13th week of gestation].

PMID- 10209553
TI  - Mathematical description of combined action of ultrasound and hyperthermia on
      yeast cells.
AB  - The inactivation of diploid yeast cells of Saccharomyces cerevisiae was studied
      after simultaneous treatment of ultrasound and hyperthermia. The existence of a
      definite temperature range was proved within which a synergistic interaction was
      determined. An optimal temperature that maximized the synergy could be
      identified. A simple mathematical model of synergistic interaction of damages
      produced by ultrasound and high temperature has been proposed. The model suggests
      that synergism is expected from the additional lethal damage arising from the
      interaction of sub-lesions induced by both agents. The model allows quantitative
      analysis of the combined action of two agents used to be performed, and predicts
      the greatest value of the synergistic effect and conditions under which it can be
      achieved.

PMID- 10209554
TI  - A multi-gate time-of-flight technique for estimation of temperature distribution
      in heated tissue: theory and computer simulation.
AB  - Non-invasive determination of temperature distribution in biological media is
      important in many heating-related studies, such as thermal treatment. In this
      paper, we present an in vitro ultrasound technique for estimation of temperature
      distribution in heated tissue. Our technique consists of two major steps: (1)
      using multiple time gates to track echo signals scattered from tissue regions at
      different depths; (2) estimating temperature distribution based on heating
      induced changes of arrival times of echo signals scattered from the targeted
      tissue regions. We use the conventional cross-correlation approach to track
      echoes. For temperature estimation, we have developed an iterative method that
      takes into account the influences of thermal expansion and heating-induced change
      in the speed of sound on the time of flight. We have introduced a concept of
      thermal sensitivity of the time of flight and used it to derive a theoretical
      formula that relates the achievable accuracy on the estimation of tissue
      temperature to seven parameters. The seven parameters are tissue thermal
      sensitivity of the time of flight, signal-to-noise ratio, bandwidth and center
      frequency of the signal, degree of signal decorrelation induced by changes in
      tissue physical properties during tissue heating, and widths and spacing of the
      time gates. We tested our technique by computer simulation, using a random
      discrete scatterer model and temperature distribution data acquired in our laser
      heating experiments on prostate tissue of live dog. Simulation results showed
      that our technique could accurately estimate the temperature distribution in the
      heated tissue. Our technique is fast in terms of computation and could be used as
      a research tool for in vitro real-time monitoring of temperature distribution in
      tissue under hyperthermal heating.

PMID- 10209555
TI  - Hormonal aspects of epithelial ovarian cancer: review of epidemiological
      evidence.
AB  - Epithelial ovarian cancer is fairly common with high rates in Scandinavia,
      intermediate rates in western Europe and North America and low rates in the
      developing countries and in Japan. The 5-year survival rate is less than 40%.
      Increasing parity consistently gives a strong protection against epithelial
      ovarian cancer. A lesser degree of protection is probably derived from incomplete
      pregnancies and lactation. Ages at menarche and menopause are most probably weak
      predictors of epithelial ovarian cancer risk. Ever users of oral contraceptives
      (OC) have 30% lower risk compared to never users. The protection increases with
      duration of OC use, being about 50% after 5 years. The reduced risk among past OC
      users persists for at least 10 years after cessation of use. Results concerning
      hormone replacement therapy (HRT) and epithelial ovarian cancer risk are
      conflicting, but most data point to a weak or no association, but as an
      increasing number of women use HRT it still seems important to resolve any
      potential effect. Infertility adds to epithelial ovarian cancer risk in
      nulliparous women, while temporary fertility problems in parous women do not
      appear to increase risk. A possible independent risk effect of fertility drug use
      has not been easy to assess and remains unresolved. It has been particularly
      difficult to separate the effects of fertility drugs from those of infertility.
      Tubal ligation and hysterectomy convey protection against epithelial ovarian
      cancer, possibly through a suppressed ovarian hormone production. The causes of
      epithelial ovarian cancer are poorly understood, but reproductive hormones are
      thought to be involved in the aetiology. For a long time the 'incessant' and
      'gonadotrophin' hypotheses have been promoted in relation to carcinogenesis. Both
      hypotheses find support in ovarian cancer epidemiology, and recent progress in
      molecular biology adds to the understanding of possible aetiological mechanisms.
      Another hypothesis focuses on the retrograde transport of contaminants or
      carcinogens through the Fallopian tubes. It is important to establish if the same
      risk factors apply to the various histological types of ovarian cancer, as
      particularly the mucinous ovarian tumours seem to present with different risk
      factors. Another question to resolve is if sporadic vs. inherited cases carry
      distinct risk profiles. As the hypotheses above do not explain all of the results
      derived from ovarian cancer epidemiology, there is a need to test additional
      hypotheses to possibly define preventive programmes and to come closer to the
      cause of ovarian cancer.

PMID- 10209556
TI  - Conn's syndrome: no longer a needle in a haystack?

PMID- 10209557
TI  - Heterogeneous haemodynamics in acromegaly: evidence of endothelial dysfunction?

PMID- 10209558
TI  - Screening for primary aldosteronism with a logistic multivariate discriminant
      analysis.
AB  - OBJECTIVE: Primary aldosteronism (PA) is the most common endocrine cause of
      curable hypertension, but no single test unequivocally identifies it.
      Accordingly, we investigated the usefulness of a logistic multivariate
      discriminant analysis (MDA) approach for PA screening. DESIGN: Generation of a
      logistic MDA function based on retrospective analysis of biochemical tests in a
      large cohort of referred patients with/without confirmed Conn's adenoma (CA),
      followed by prospective validation of the model. PATIENTS: We investigated 574
      selected hypertensives: 206 (32 with and 174 without CA) retrospectively, 48
      (with a 13% prevalence of CA) prospectively for the validation of the model, and
      320 referred hypertensives (with a 3.4% prevalence of CA) similarly evaluated.
      Patients were referred to a specialised centre for hypertension (4th Clinica
      Medica--University of Padua) and to a department of Internal Medicine of a
      regional hospital (Reggio Emilia). MEASUREMENTS: In all patients we measured
      several demographic and biochemical variables and performed a captopril test. A
      stepwise analysis of variance, based on a model fitted with several different
      variables, identified baseline (sALDO) and captopril-suppressed plasma
      aldosterone (cALDO), supine plasma renin activity (sPRA) and K+ as the most
      informative. Therefore, two models of logistic MDA with sPRA, K+, and either
      sALDO (model A) or cALDO (model B) were developed and used. ROC analysis was also
      performed to assess the optimal cut-off values. RESULTS: The model B of MDA
      provided the best performance and identified CA with 100% sensitivity and 81%
      accuracy. When used prospectively it showed 100% sensitivity, both in the Padua
      (88% accuracy) and in the Reggio Emilia series (90% accuracy). However, at both
      institutions most patients with idiopathic hyperaldosteronism (IHA) were also
      detected. CONCLUSIONS: Thus, although developed from patients with confirmed
      Conn's adenoma, a strategy based on multivariate discriminant analysis can be
      used prospectively for accurate screening for primary aldosteronism. Furthermore,
      it was proven to be accurate and applicable to patients tested with similar
      modalities at a different institution. Although this approach did not provide a
      clear-cut discrimination of Conn's adenoma from idiopathic hyperaldosteronism, it
      may avoid unnecessary and costly further testing in patients with a low
      probability of primary aldosteronism.

PMID- 10209559
TI  - Decreased regional blood flow in patients with acromegaly.
AB  - BACKGROUND AND AIMS: One-third of acromegalic patients have hypertension.
      Acromegaly is also associated with intrinsic cardiac abnormalities known
      collectively as a hyperkinetic heart syndrome, which is characterized by an
      increased cardiac index and decreased systemic vascular resistance. As a result,
      blood flow should be increased in the regional vascular beds of acromegalic
      patients. The aim of the study was to measure, using direct methods, blood flow
      and vascular resistance at the level of the brachial artery in acromegalic
      patients with a confirmed hyperkinetic heart syndrome. PATIENTS AND CONTROLS:
      Twelve patients with active acromegaly (five females, seven males; mean (+/- SD)
      age, 43 +/- 10 years) were studied. Twelve age- and sex-matched normal subjects
      served as controls. METHODS: Right heart catheterization was used to measure the
      cardiac index and stroke volume and to calculate systemic vascular resistance in
      the acromegalic patients. Brachial haemodynamics were evaluated with a two
      dimensional pulsed Doppler system (double transducer probe and range-gated time
      system of reception). The mean diameter of the brachial artery and mean blood
      velocity were measured and used to calculate mean blood flow. Vascular resistance
      was calculated in the brachial artery as the mean arterial pressure/blood flow
      ratio. RESULTS: Age, body weight, height, body surface area and heart rate were
      similar in the acromegalic patients and controls, while mean arterial pressure
      was higher in patients. The cardiac index and stroke volume were increased in the
      acromegalic patients, at 4.08 +/- 0.47 (mean +/- SD) l/min/m2 body surface area
      and 116.7 +/- 19.4 ml, respectively, while systemic vascular resistance was low
      (12.5 +/- 2.1 U). Brachial artery diameter was similar in the patients and
      controls. Brachial artery mean blood velocity (P < 0.01) and mean blood flow (P <
      0.05) were lower in the patients than in the controls (3.35 +/- 1.26 vs. 5.12 +/-
      1.74 cm/s, and 16.4 +/- 9.4 vs. 25.6 +/- 11.6 ml/min/m2, respectively). The
      higher mean arterial pressure and lower mean blood flow resulted in higher
      forearm vascular resistance in the patients than in the controls (132 +/- 61 vs.
      83.8 +/- 47 mmHg/ml/s/m2, respectively, P < 0.01). CONCLUSION: While cardiac
      output is increased and systemic vascular resistance is decreased in active
      acromegaly, direct measurement of brachial artery haemodynamics showed lower
      regional blood flow and increased local resistance relative to healthy controls.
      These results suggest a heterogeneous distribution of cardiac output in
      acromegaly.

PMID- 10209560
TI  - Growth in children with craniopharyngioma following surgery.
AB  - OBJECTIVE: Hypopituitarism, including severe GH deficiency, is an almost
      inevitable outcome of craniopharyngioma. However, some GH deficient children with
      this tumour may grow normally or even have accelerated growth postoperatively. To
      study this phenomenon we have investigated the endocrine status, including IGF-1
      and its binding proteins IGFBP-1 and IGFBP3, in children referred for follow-up
      at various time intervals after surgery. PATIENTS: Twenty-five patients (14 boys
      and 11 girls, aged 3.8-18.9 years), were studied on 34 occasions between 0.5 to
      10.8 years after surgery. The tumour was intrasellar in 11 cases and suprasellar
      in 14. METHODS: Height and height velocity were recorded as SDS values. Body mass
      index (BMI) was calculated as weight/height2. GH secretory status was evaluated
      by stimulation both with oral clonidine and with GH releasing hormone. Serum
      insulin (INS) levels were studied following an oral glucose load. IGF-1, IGFBP-3,
      IGFBP-1 and prolactin serum concentrations were evaluated in fasting samples. All
      hormones were measured by radioimmunoassay. RESULTS: All patients had growth
      hormone (GH) deficiency. Height (HtSDSCA) and height velocity SDS for
      chronological age (HVSDSCA) decreased progressively after surgery (r = -0.47, P =
      0.005, and r = -0.4, P = 0.032, respectively) but four patients had normal
      HtSDSCA 6.1 to 10.8 years following their first surgery. There was a significant
      correlation between BMI and HtSDSCA (r = 0.37, P = 0.03). BMI in children with
      suprasellar craniopharyngioma was significantly greater than that in patients
      with intrasellar tumour (23.3 +/- 7.0 vs. 17.3 +/- 1.4 kg/m2; P = 0.001). In 13
      of 33 cases oral glucose load was accompanied by hyperinsulinaemia with serum INS
      levels greater than 50 mU/l. The mean area under the curve (AUC) of INS after
      glucose load (INSAUC) in the suprasellar group was greater than in the patients
      with intrasellar lesion (6945.5 +/- 4411.8 vs. 2495.5 +/- 1768.8 mU/l. min P = 0
      001). The log INSAUC correlated significantly with HtSDSCA (0.37, P = 0.03).
      Fasting serum IGF-1 and IGFBP3 levels were normal in 8 and 12 of the 31
      measurements, respectively. Both IGF-1SDS and IGFBP-3SDS correlated significantly
      with HtSDSCA (r = 0.77, P = 0.0002 and r = 0.65, P = 0.0001, respectively) and
      the log INSAUC (r = 0.39, P = 0.035, r = 0.56, P = 0.002, respectively). As
      determined by forward stepwise regression analysis, IGF-1SDS was the single most
      important predictor of HtSDSCA (R2 = 0.33, P = 0.001) in the subset mode.
      CONCLUSION: A few children with craniopharyngioma grew normally after surgery, in
      spite of being GH-deficient. This growth phenomenon, which is usually accompanied
      by obesity, was more common in patients with suprasellar tumour and is likely to
      be associated with the effect of IGF-1 bioavailability, which, in turn, may be
      modulated largely by insulin.

PMID- 10209561
TI  - Recombinant human insulin-like growth factor-I (rhIGF-I) therapy in adults with
      type 1 diabetes mellitus: effects on IGFs, IGF-binding proteins, glucose levels
      and insulin treatment.
AB  - OBJECTIVE: Insulin-like growth factor-I (IGF-I) has both insulin-like and
      anabolic actions but unlike insulin, IGF-I circulates bound to a number of
      specific binding proteins that regulate its availability and activity. Patients
      with type 1 diabetes mellitus have low levels of circulating IGF-I despite
      increased growth hormone (GH) secretion, and are a group that may benefit from
      rhIGF-I therapy. Understanding the relationship between IGF-I and its binding
      proteins is necessary to appreciate the actions of exogenously administered rhIGF
      I. Therefore, we examined the effects of 19 days' subcutaneous administration of
      rhIGF-I (50 micrograms/kg BID) on the levels of IGF-I, IGF-II and the IGF-binding
      proteins (IGFBPs), as well as the daily dose of insulin necessary to maintain
      glycaemic control in patients with type 1 diabetes mellitus. DESIGN AND PATIENTS:
      This was an open study, and the patients were studied initially while resident
      (days 1-5) in the hospital and thereafter (days 6-24) as outpatients. Serum was
      collected at baseline and at intervals throughout the study for the measurement
      of total IGF-I, IGF-II, IGFBP-1, -2, -3, free insulin and growth hormone (GH).
      Daily insulin doses and glucometer readings were recorded throughout the study.
      The changes in each of these variables were examined. The subjects were six
      adults (35.3 +/- 4.0 years, mean +/- SE), with type 1 diabetes, and all had
      reasonable glycaemic control (HbA1c 7.2 +/- 0.5%). RESULTS: rhIGF-I
      administration increased circulating total IGF-I over two-fold (15.3 +/- 1.9 vs.
      33.7 +/- 5.4 nmol/l, mean +/- SEM, P < 0.01, day 1 vs. day 20) and decreased
      plasma IGF-II concentration (85.0 +/- 4.7 vs. 50.6 +/- 4.7 nmol/l, P < 0.01, day
      1 vs. day 20). The dose of insulin required for adequate glycaemic control
      decreased significantly during rhIGF-I therapy (46 +/- 7 vs. 31 +/- 8 U/day, P <
      0.05, day -1 vs. day 19), as did the fasting free insulin concentration (8.4 +/-
      1.5 vs. 5.0 +/- 0.8 mU/l, P < 0.05, baseline vs. day 5). IGFBP-2 concentration
      increased (388 +/- 115 vs. 758 +/- 219 micrograms/l, P < 0.05, day 1 vs. day 20),
      but IGFBP-1 and IGFBP-3 were unchanged during rhIGF-I treatment. Mean nocturnal
      GH concentration decreased (12.7 +/- 3.3 vs. 3.8 +/- 0.9 mU/l, P = 0.05) after 4
      days' rhIGF-I therapy. CONCLUSION: Twice daily rhIGF-I therapy in adults with
      type 1 diabetes resulted in an increase in circulating IGF-I with a reciprocal
      decrease in IGF-II, and a marked elevation of IGFBP-2 concentration. The levels
      of IGFBP-1 and -3 were not dramatically changed despite a reduction in the
      concentration of serum free insulin, and a large decrease in the requirement for
      insulin. The mechanisms behind these changes remains unclear but alterations in
      circulating levels of of IGFBPs may alter IGF-I bioactivity. If rhIGF-I is to
      have an application in the management of adults with type 1 diabetes, further
      work is necessary to determine the metabolic consequences of the alterations seen
      in the IGFs and their binding proteins following rhIGF-I administration.

PMID- 10209562
TI  - Effects of growth hormone treatment on serum levels of insulin-like growth
      factors (IGFs) and IGF binding proteins 1-4 in postmenopausal women.
AB  - BACKGROUND AND OBJECTIVE: Insulin-like growth factor binding proteins (IGFBPs)
      modulate the actions and bioavailability of insulin-like growth factors (IGFs),
      however, their regulation in vivo is incompletely understood. In this study we
      investigated the effects of different doses of growth hormone (GH) on circulating
      levels of IGFs and IGFBPs. DESIGN: The study was double-blind and placebo
      controlled. Patients were treated with either GH in doses of 0.05, 0.10, or 0.20
      lU/kg/day of placebo for one week. PATIENTS: Forty post-menopausal women aged 52
      73 years with low bone mass. MEASUREMENTS: Serum IGF-I and IGF-II were measured
      by RIA while IGFBP-1-3 were measured by Western ligand blot (WLB) and compared
      with determinations by specific immunoassays. IGFBP-4 was measured by WLB alone.
      RESULTS: Both IGF-I (P < 0.001) and IGF-II (P < 0.01) increased significantly
      during GH treatment. Additionally, IGFBP-1 (P < 0.001) and IGFBP-2 (P < 0.001)
      decreased significantly while IGFBP-3 (P < 0.001) and IGFBP-4 (P < 0.05)
      increased all in a dose-dependent manner. Stepwise (backwards) multiple
      regression analyses showed that the changes in IGF-I and IGF-II, and age
      correlated with the change in serum IGFBP-1. Both GH-dosage, the increase in IGF
      II, and body mass index correlated with the decrease in IGFBP-2. Furthermore, the
      increase in serum IGF-I, IGF-II, and triiodothyronine correlated with the
      increase in IGFBP-3. Moreover, GH-dosage correlated with the increase in serum
      IGFBP-4. CONCLUSION: GH significantly increased serum IGF-I, IGF-II, IGFBP-3, and
      IGFBP-4 and decreased serum IGFBP-1 and IGFBP-2 in post-menopausal women.

PMID- 10209563
TI  - The IGF-I response to very low rhGH doses is preserved in human ageing.
AB  - OBJECTIVES: The activity of the GH/IGF-I axis varies during life and is clearly
      reduced in the elderly. In fact, GH, IGF-I and IGFBP-3 levels in older people are
      clearly reduced and similar to those observed in patients with GH deficiency. The
      declining activity of the GH/IGF-I axis with advancing age may contribute to
      changes in body composition, structure, function and metabolism. In fact,
      treatment with pharmacological doses of rhGH restored plasma IGF-I levels,
      increased lean body mass and muscle strength while decreased adipose tissue mass
      in healthy elderly subjects. At present it is unclear whether peripheral GH
      sensitivity is preserved in aging. To clarify this point, we aimed to verify the
      effect of both single dose and short term treatment with very low rhGH doses on
      the IGF-I levels in normal elderly subjects. Normal young adults were studied as
      controls. DESIGN: We studied the IGF-I response to rhGH administration after
      single (20 micrograms/kg s.c.) or repeated administrations (5 micrograms/kg s.c.
      for 4 days) in two groups of young and elderly subjects. SUBJECTS: Twenty-seven
      healthy elderly (ES, 14 F and 13 M, age mean +/- SEM: 69.4 +/- 1.3 years, BMI:
      23.9 +/- 0.5 kg/m2) and 21 young adult subjects (YS, 12 F and 9 M, 29.8 +/- 1.2
      years, 23.8 +/- 0.5 kg/m2) were studied, divided into two groups. MEASUREMENTS:
      Group 1: blood samples for IGF-I and IGFBP-3 assay were drawn basally and 12 h
      after rhGH administration (20 micrograms/kg). Group 2: blood samples for IGF-I,
      IGFBP-3, glucose and insulin assays were drawn basally, 12 h after the first and
      the last rhGH administration (5 micrograms/kg). Free T3 (fT3), free T4 (fT4) and
      TSH levels were also assayed basally and after the last rhGH administration;
      oestradiol and testosterone levels were measured basally. RESULTS: Basal IGF-I
      levels were lower in ES (whole group) than in YS (whole group) (123.1 +/- 8.9 vs.
      230.4 +/- 16.1 micrograms/l, P < 0.001) while IGFBP-3 levels in the two groups
      were similar (2.7 +/- 0.2 vs. 3.1 +/- 0.2 mg/l). No sex-related differences in
      IGF-I and IGFBP-3 levels were recorded in either group. Group 1: the single
      administration of 20 micrograms/kg rhGH induced a significant (P < 0.001) IGF-I
      rise both in YS (318.0 +/- 25.3 vs. 256.0 +/- 21.6 micrograms/l) and ES (187.2 +/
      16.8 vs. 100.4 +/- 9.5 micrograms/l). IGF-I levels after rhGH in ES persisted
      lower than those in YS (P < 0.001), but the percentage IGF-I increase after rhGH
      was higher (P < 0.001) in ES (91.6 +/- 12.9%) than in YS (23.9 +/- 5.0%)
      subjects. Both in YS and ES IGFBP-3 levels were significantly increased to the
      same extent by 20 micrograms/kg rhGH (3.0 +/- 0.2 vs. 2.3 +/- 0.2 mg/l; 2.9 +/-
      0.2 vs. 2.6 +/- 0.2 mg/l, P < 0.001 vs. baseline). Group 2: basal glucose,
      insulin, fT3, fT4 and TSH levels in YS and ES were similar; testosterone levels
      in aged and young men were similar while oestradiol levels in aged women were
      lower (P < 0.01) than in the young ones. IGF-I levels were significantly
      increased 12 h after the first administration of 5 micrograms/kg rhGH both in ES
      (166.6 +/- 15.7 vs. 138.3 +/- 12.1 micrograms/l, P < 0.03) and YS (272.2 +/- 16.1
      vs. 230.4 +/- 16.1 micrograms/l, P < 0.001). Twelve hours after the last rhGH
      administration IGF-I levels were further increased (P < 0.001) both in ES (208.7
      +/- 21.1 micrograms/l) and YS (301.7 +/- 17.6 micrograms/l). IGF-I levels in ES
      persisted lower than those in YS at each time point (P < 0.001); however, the
      percentage IGF-I increase after rhGH in ES and YS was similar (after the first
      administration: 22.4 +/- 5.1 vs. 21.7 +/- 5.1%; after the last administration:
      52.9 +/- 9.5 vs. 39.5 +/- 9.9%). No significant variation in IGFBP-3, glucose,
      insulin, fT3, fT4 or TSH levels was recorded in either ES or YS. CONCLUSIONS: Our
      data demonstrate that IGF-I levels in aging are reduced but the peripheral
      sensitivity to rhGH is preserved. In fact, in aged subjects the percentage rhGH
      induced IGF-I increase is similar or even highe

PMID- 10209564
TI  - One-year follow-up of quality of life in adults with untreated growth hormone
      deficiency.
AB  - OBJECTIVE: The aim of the study was to evaluate the impact on health-related
      quality of life (HRQoL) in untreated GHD patients using the disease-specific
      Assessment of Growth Hormone Deficiency in Adults (AGHDA) questionnaire. DESIGN
      AND PATIENTS: A cohort of 356 consecutive adult GHD patients, diagnosed after the
      age of 18 years, from the endocrinology units of 37 Spanish hospitals were
      included over a 6-month period in a longitudinal observational quality-of-life
      study. In addition, patients' HRQoL scores were compared to those obtained from a
      random sample of 963 subjects from the general population recruited by trained
      interviewers in a 6-month period and matched by age and sex to figures of the
      1991 Spanish census. MEASUREMENTS: Patients were evaluated at baseline and after
      12-months. Socio-demographic and health variables such as age, sex, level of
      education, income level, number of chronic diseases and self-reported health
      status were recorded at baseline and follow-up visits. Patients underwent
      physical and analytical examination and completed the AGHDA questionnaire. A
      survey including socio-demographic, self-reported health status and the AGHDA
      questionnaire was administered at the individuals' homes. RESULTS: Mean score for
      patients at baseline was 9.4 (CI = 8.4-10.4) and at 12 months 10 (CI = 8.8-11).
      HRQoL was worse in the case of older patients with a low level of education,
      lower income levels, reporting having an associated chronic disease and poor self
      reported health status (P < 0.01). Untreated GHD patients maintain or slightly
      worsen their HRQoL after 12 months of follow-up, with high individual
      variability. Although AGHDA scores worsened during the observation period,
      differences were not statistically significant. AGHDA mean score in controls was
      5.49 (CI = 5.27-5.71). Comparison of the mean AGHDA scores between patients and
      controls previously standardized by level of education and age were statistically
      different (P < 0.01), indicating that patients declared a worse HRQoL than the
      general population except for those aged 60-69 years. GHD patients presented a
      deterioration in HRQoL almost double that of the general population. CONCLUSIONS:
      These results permit comparison of patients' scores against reference scores with
      regard to the desirable effect of treatment. Future use of the AGHDA
      questionnaire in clinical trials should try to establish a relationship between
      biological and HRQoL changes.

PMID- 10209565
TI  - Comparison of the diagnostic utility of the simplified and standard i.m. glucagon
      stimulation test (IMGST).
AB  - OBJECTIVE: To compare the peak GH and cortisol responses to the simplified and
      standard i.m. glucagon stimulation test (IMGST) in order to determine whether the
      use of a simplified form of this test results in a loss of diagnostic utility.
      PATIENT AND DESIGN: A retrospective study of 35 consecutive patients with
      pituitary disease who underwent a standard IMGST to measure GH (n = 34) or
      cortisol (n = 21) reserve at the programmed investigation unit of the Northern
      General Hospital, Sheffield. MEASUREMENTS: Cortisol, glucose and GH levels were
      measured at baseline and 30, 60, 90, 120, 150, 180, 210 and 240 min during the
      standard IMGST. We used the hormone levels at baseline, 150 and 180 min for the
      simplified IMGST and compared the cortisol and GH responses achieved. RESULTS:
      The median (range) peak GH and cortisol responses to simplified and standard
      IMGST were comparable 4.2 (0.5-47.5) vs 5.4 (0.5-47.5) mU/l (P = 0.75) and 635
      (306-1669) vs 647 (306-1669) nmol/l (P = 0.801), respectively. Using the standard
      'cut-off' points to assess GH (9 mU/l) or cortisol deficiency (580 nmol/l) there
      was no significant loss of diagnostic utility (P = 0.98 and P = 1.00,
      respectively). CONCLUSIONS: The simplified and standard IMGST have a similar
      diagnostic utility. The simplified IMGST could replace the standard IMGST as a
      screening test for GH and cortisol reserve in pituitary disease. The insulin
      induced hypoglycaemia stress test can be reserved for cases in which a second
      assessment of pituitary reserve is clinically indicated or because of an
      indeterminate biochemical result.

PMID- 10209566
TI  - Secondary adrenal insufficiency associated with autoimmune disorders: a report of
      twenty-five cases.
AB  - OBJECTIVE: Addison's disease is frequently a component of autoimmune
      polyendocrinopathies while secondary adrenal insufficiency associated with
      autoimmune disorders is believed to be a rare event. We present a series of
      patients with secondary adrenal insufficiency coexisting with autoimmune diseases
      and/or antithyroid autoantibodies. DESIGN AND PATIENTS: Among a group of 102
      patients with secondary adrenal failure of unknown origin diagnosed at the
      Department of Endocrinology of the Centre for Postgraduate Medical Education
      (Warsaw, Poland) we have identified a group with associated autoimmune disorders.
      Thyroid abnormalities occurred most frequently. Other diseases included insulin
      dependent diabetes mellitus, pernicious anaemia, vitiligo, premature ovarian
      failure and autoimmune thrombocytopaenia. There were 23 women and one man aged 17
      72 years at the time of investigation. Additionally, we included a woman with
      Addison's disease in whom the ACTH deficiency appeared 18 years after the onset
      of primary adrenal hypofunction. MEASUREMENTS: Pituitary-adrenal function tests
      comprised urinary excretion of 17-hydroxycorticosteroids in basal conditions and
      during a 2-day tetracosactrin test, plasma concentrations of ACTH and cortisol,
      and a 2-day metyrapone test (in eight cases). Thyroid function and immunity tests
      were: TSH, thyroxine, the antithyroglobulin, antimicrosomal and anti-peroxidase
      autoantibodies. Other endocrine studies included: serum LH, FSH and PRL. RESULTS:
      The 17-hydroxycorticosteroid values, both basally and during stimulation tests
      were consistent with a diagnosis of secondary adrenal insufficiency. Serum
      cortisol and plasma ACTH concentrations were low. In 14 patients primary
      hypothyroidism was confirmed by low T4 levels. In three patients subclinical
      primary hypothyroidism was revealed (elevated TSH levels). Three patients who had
      a past history of Graves' disease were euthyroid at the time of investigation.
      Twenty-three patients had antibodies against peroxidase. Most patients had
      gonadotrophins and PRL values within normal limits. CONCLUSIONS: The co-existence
      of autoimmune disorders with secondary adrenal insufficiency suggests an
      autoimmune aetiology for the ACTH deficiency.

PMID- 10209567
TI  - Dual facets of hyponatraemia and arginine vasopressin in patients with ACTH
      deficiency.
AB  - OBJECTIVE: Hyponatraemia is often observed in patients with ACTH deficiency who
      are thought not to suffer from volume depletion. Their high plasma AVP levels
      relative to plasma osmolality are presumed to be maintained by non-osmotic
      mechanisms. We attempted to assess volume status from changes in selected
      clinical measurements related to body fluid balance in the course of i.v. fluid
      supplementation and following glucocorticoid (GC) replacement in ACTH-deficient
      patients, and to interpret plasma AVP levels in the context of the estimated
      volume status. PATIENTS AND DESIGN: This report consists of three parts. First,
      an ACTH-deficient patient with hyponatraemia and volume depletion who was
      followed through volume replacement to recovery after GC replacement is described
      (case report). Secondly, medical records of five ACTH-deficient patients with
      hypovolaemia and hyponatraemia were surveyed retrospectively to observe changes
      in serum levels of sodium, uric acid (UA) and haematocrit (Hct) following i.v.
      fluid supplementation of low sodium content (retrospective study). Thirdly, five
      ACTH-deficient patients with or without overt dehydration were studied with
      regard to body weight, blood pressure, serum sodium, total proteins, Hct and
      blood urea nitrogen before and after GC replacement (prospective study). Plasma
      AVP levels were measured after i.v. fluid supplementation without GC replacement
      in the patients of the retrospective study, and before and after GC replacement
      in the patients of the prospective study. RESULTS: The first patient became more
      hyponatraemic after i.v. fluid supplementation and recovered ultimately from
      hyponatraemia after GC replacement. In five patients studied retrospectively, the
      serum sodium levels fell progressively following i.v. fluid supplementation,
      concurrent with reduction in UA levels and Hct, which indicated the dilutional
      nature of the hyponatraemia. In the patients observed prospectively, the
      accumulation of fluid and sodium was indicated by a rise in body weight, blood
      pressure and serum sodium levels and a decline in Hct and total proteins after GC
      replacement. Plasma AVP levels rose similarly in patients with dilutional
      hyponatraemia and in patients with borderline hyponatraemia before GC
      replacement. CONCLUSION: Patients with untreated ACTH deficiency may have either
      of two kinds of hyponatraemia--i.e. borderline hyponatraemia associated with
      subclinical hypovolaemia, or dilutional hyponatraemia. Similarity of plasma AVP
      levels in two hyponatraemic states suggests their AVP secretion is regulated by
      non-osmotic, non-volume mechanisms, possibly released from GC suppression at low
      plasma osmolality.

PMID- 10209568
TI  - The efficacy of DDAVP is related to the circadian rhythm of urine output in
      patients with persisting nocturnal enuresis.
AB  - OBJECTIVE: Desmopressin may be a useful treatment in some, but not all, patients
      with nocturnal enuresis. We have evaluated a relation between nocturnal urine
      output in patients with primary monosymptomatic nocturnal enuresis and the
      treatment response to synthetic vasopressin. DESIGN: Adolescent or adult
      enuretics and normal subjects were enrolled in the study and admitted to hospital
      for a 24 hour investigation of the diurnal variation in urine output, plasma
      vasopressin (AVP) and plasma atrial natriuretic peptide (ANP). The enuretics were
      characterized prior to investigation as either 1-desamino-8-D-arginine
      vasopressin (DDAVP) responders or non-responders. During admission the fluid
      intake was restricted to 25 ml/kg per day. PATIENTS: Twenty-four patients (15-37
      years) with primary monosymptomatic nocturnal enuresis and 9 normal subjects (24
      31 years). MEASUREMENTS: Circulating levels of AVP, ANP, plasma electrolytes and
      plasma osmolality were measured (1400, 2000, 2300, 0200, 0500 and 0800 hours)
      together with urine volume, urine osmolality and urine electrolytes during
      daytime and nighttime. Tubular reabsorptive capacity for water, osmoles and
      creatinine were assessed as well as urinary and fractional excretion rates of
      sodium and potassium. RESULTS: Controls and DDAVP non-responders had a
      significant decrease in urine output at night concomitant with a significant
      plasma AVP amplitude in peak/nadir values although both groups lacked a
      significant nocturnal increase in AVP. In contrast, in DDAVP responders there was
      no circadian variation in urine output and thus a nocturnal polyuria together
      with no oscillation in plasma AVP. The DDAVP responding group had a nocturnal
      urine production significantly larger than the two other groups. However, the
      mean 24 hour AVP levels were similar in all groups. The excessive urine
      production at night in DDAVP responders was accompanied by nocturnal natriuresis
      due to an increased fractional excretion of sodium. In contrast, nocturnal
      antidiuresis in controls and DDAVP non-responding enuretics coincided with
      diminished sodium excretion. Average ANP levels were elevated in both enuretic
      groups compared to normals, whereas a circadian variation was detected only in
      the latter. CONCLUSION: It is concluded that DDAVP responsiveness is linked to
      the nocturnal urine production and that no pathophysiological role can be
      ascribed to AVP or ANP in DDAVP refractory adolescent and adult enuretics.
      Moreover, it is suggested that an abnormal tubular handling of sodium may
      contribute to the nocturnal polyuria seen in DDAVP responders.

PMID- 10209569
TI  - Serum oestradiol and oestrogen-receptor gene polymorphism are associated with
      bone mineral density independently of serum testosterone in normal males.
AB  - OBJECTIVES: The physiological effects of oestrogens on bone in men were largely
      unanticipated until recently, when oestrogen deficiency in males with aromatase
      deficiency and oestrogen resistance was found to cause osteoporosis and delayed
      fusion of epiphyses despite sufficient serum testosterone. This raises the
      possibility that in normal men oestrogens rather than androgens are of
      physiological importance in bone maturation. In the present study, we examined
      the association of serum oestradiol (E2) compared to that of free testosterone
      (FT) with bone mineral density (BMD) in normal men. The effect of oestrogen
      receptor (ER) gene polymorphism on BMD in men was also addressed. SUBJECTS:
      Eighty-one Thai men aged 20-79 years. All were healthy and did not take
      medication which may affect calcium and bone metabolism. BMD was assessed by
      DEXA. Dietary calcium was assessed by a 3-day dietary record. Serum E2 and FT
      concentrations were measured by radioimmunoassay. Polymorphism at intron 1 of the
      alpha isoform of ER gene was determined by PCR-RFLP. Small p represents the
      presence of the restriction site while capital P indicates the absence of the
      restriction site. RESULTS: Serum FT decreased with increasing age (r = -0.58, P <
      0.0001) while E2 did not. However, there was a positive association between E2
      and FT (r = 0.28, P < 0.05). Serum FT was related to BMD at femoral neck (r =
      0.26, P < 0.05) and Ward's triangle (r = 0.30, P < 0.01) while E2 was related to
      BMD at anteroposterior (AP) lumbar spine (r = 0.29, P < 0.05), femoral neck (r =
      0.23, P < 0.05) and femoral trochanter (r = 0.27, P < 0.05). Besides FT and E2,
      age, body weight, fat mass and fat-free mass were also correlated to BMD at
      various skeletal sites. Using stepwise multiple linear regression to control for
      the confounding effects among these factors, fat-free mass was found to be
      strongly associated with BMD at most skeletal sites. Serum E2 was related to BMD
      independently of other factors including FT at AP lumbar spine (r = 0.22, P <
      0.05), femoral neck (r = 0.26, P < 0.01), femoral trochanter (r = 0.22, P < 0.05)
      and Ward's triangle (r = 0.26, P < 0.01) while serum FT was not associated with
      BMD at any site after controlling for E2 and other related factors. Concerning ER
      alpha gene polymorphism, 27 (33.3%) of the subjects had pp genotype, while 42
      (51.9%) and 12 (14.8%) Pp and PP genotypes, respectively. After controlling for
      age, body weight, fat mass, fat-free mass, calcium intake, FT and E2, the
      presence of P allele was associated with higher BMD at AP L2-L4 (P < 0.05).
      CONCLUSIONS: Serum oestradiol is more related to bone mass than free testosterone
      in normal men. Oestrogen-receptor gene polymorphism is also associated with bone
      mass in men independently of oestradiol levels. Serum oestradiol together with
      oestrogen-receptor genotype may partly determine bone mass in males.

PMID- 10209570
TI  - The effects of oestrogen exposure on bone mass in male to female transsexuals.
AB  - OBJECTIVE: The importance of oestrogen on bone mineral density (BMD) in males was
      suggested by reports of patients with oestrogen resistance and aromatase
      deficiency who demonstrated osteoporosis and epiphyseal plate maturation defect
      despite high testosterone levels. In the present study, we examined the effects
      of oestrogen exposure on BMD in transsexual men. DESIGN: Cross-sectional study of
      BMD in male to female transsexuals. PATIENTS: Subjects consisted of two groups of
      transsexual male dancers aged 16-34 years who did not receive transsexual
      operations (n = 28). Group 1 (n = 11) and group 2 (n = 17) had used oestrogen for
      2 years or less and more than 2 years, respectively. Twenty-four healthy adult
      males served as controls. RESULTS: Signs of feminization were presented in both
      group 1 and group 2, with Tanner's stage II-III breast development. BMD at
      various sites were correlated only to body weight and not to smoking or milk
      consumption. After controlling for body weight, it was found that group 2 had
      significantly higher BMD at L2-4 than controls (1.22 +/- 0.03 vs. 1.14 +/- 0.03
      g/cm2, P < 0.05) and group 1 (1.22 +/- 0.03 vs. 1.08 +/- 0.04 g/cm2, P < 0.05).
      BMD at femoral neck was also higher in group 2 compared to controls (1.10 +/-
      0.03 vs. 1.01 +/- 0.03 g/cm2, P < 0.05) and group 1 (1.10 +/- 0.03 vs. 0.95 +/-
      0.04 g/cm2, P < 0.05). Group 1 subjects had lower BMD compared to controls at
      femoral trochanter (0.70 +/- 0.04 vs. 0.83 +/- 0.03 g/cm2, P < 0.05) and total
      femur (0.96 +/- 0.05 vs. 1.07 +/- 0.03 g/cm2, P < 0.05). CONCLUSIONS: Long-term
      oestrogen exposure transsexual men result in an increase in bone mineral density
      despite signs of feminization. This suggests that oestrogen has positive effects
      on bone density in males. The finding of the trend towards reduced bone density
      in group 1 remains unexplained.

PMID- 10209571
TI  - Aldosterone production despite absence or defectiveness of the CYP21 genes in two
      patients with salt-losing congenital adrenal hyperplasia caused by steroid 21
      hydroxylase deficiency.
AB  - Aldosterone and cortisol were found in plasma samples from two patients with salt
      losing congenital adrenal hyperplasia caused by steroid 21-hydroxylase
      deficiency. One patient had a CYP21 gene deletion on one chromosome and a
      mutation causing erroneous mRNA splicing on the other. The other patient had a
      CYP21 gene deletion on one chromosome and a large scale conversion of CYP21 to
      CYP21P on the other. All CYP21P-like genes in these patients were defective,
      since they carried a deleterious 8 bp deletion in the third exon. After HPLC
      purification of the patients' plasma samples, cortisol was no longer detectable
      in the radioimmunoassay, but aldosterone levels were still within or slightly
      above the normal reference range. Aldosterone dropped to very low levels after
      steroid replacement therapy had taken effect. In at least one of these patients,
      the genetic defect rules out normal functioning of the adrenocortical steroid 21
      hydroxylase, which implies involvement of an alternative enzyme system.

PMID- 10209572
TI  - Safety evaluation of a fungal pectinesterase enzyme preparation and its use in
      food.
AB  - The Aspergillus aculeatus pectinesterase enzyme is used to modify the texture of
      plant derived products. It is produced by A. oryzae transformed with the cloned
      full length cDNA of A. aculeatus encoding pectinesterase. It was subjected to a
      series of toxicological tests to document safety in use. The enzyme preparation
      was not found to be mutagenic in the Ames test, and did not cause chromosomal
      damage in a human lymphocyte assay. In a 13-week oral-toxicity study in rats,
      with daily dosages up to 10 g enzyme preparation kg body weight (b.w.), there
      were no adverse effects on mortality, clinical signs, body weight, food or water
      consumption, ophthalmoscopic findings, haematology or clinical chemistry. There
      were also no notable necropsy or histological findings. Statistically significant
      increases in heart weight were noted in male animals treated with 5 or 10 g
      enzyme preparation/kg b.w./day, following covariance analysis. However, this was
      not considered to be related to treatment with the enzyme preparation. The issue
      of the levels of free liberation of methanol in products processed with
      pectinesterase is addressed, and it is concluded that, from a nutritional and
      physiological point of view, free as well as bound methanol must be considered.

PMID- 10209573
TI  - Aspects of extraction, spiking and distribution in the determination of incurred
      residues of chloramphenicol in animal tissues.
AB  - Studies of distribution, extraction procedures and spiking protocols in the
      determination of incurred chloramphenicol residues in animal tissues have been
      carried out. An extraction procedure involving glucuronidase enzyme digestion was
      found to extract 10 times more incurred chloramphenicol from pig kidney than
      direct extraction without digestion. However, neither protease digestion nor
      ultrasonic probe treatment resulted in improved chloramphenicol extraction.
      Chloramphenicol was found to be inhomogeneously distributed within kidney from a
      treated pig. Highest concentrations were detected in the renal medulla. Muscle
      tissues from the same animal were found to contain a lower concentration of
      chloramphenicol residues, but no chloramphenicol residues were detectable in the
      liver. Chloramphenicol recovery from spiked pig liver was found to be lower than
      that from kidney, but was improved by the addition of piperonyl butoxide before
      extraction. This additive had no effect on recovery from spiked pig or cattle
      kidney. The implications of these results for regulatory surveillance of animal
      tissue for chloramphenicol residues are discussed.

PMID- 10209574
TI  - Effects of extraction and spiking procedures on the determination of incurred
      residues of oxytetracycline in cattle kidney.
AB  - The effects of different extraction and spiking procedures on the determination
      of incurred oxytetracycline residues in animal tissues have been investigated.
      The extraction procedures investigated--direct aqueous or organic solvent
      extraction, enzymic digestion or sonication--all gave similar results for
      incurred oxytetracycline concentration in cattle kidney after correction for
      spike recovery. There was therefore no evidence for binding or conjugation of
      oxytetracycline in this tissue. Highest recovery from spiked tissue was obtained
      using ethyl acetate as extractant. The effects of spiking procedure (spike
      contact time, spike solvent and tissue state) on recovery from spiked cattle
      kidney were also small, indicating that added oxytetracycline spike does not
      interact with the tissue.

PMID- 10209575
TI  - Evaluation of a modified EC Four Plate Method to detect antimicrobial drugs.
AB  - This paper describes a modification of the EC Four Plate Method based on
      microbial growth inhibition of Bacillus subtilis on agar medium at pH 6.0, 7.2
      and 8.0 and Micrococcus luteus at pH 8.0 developed to cope with large numbers of
      samples. The method's performance was evaluated by determining the Minimum
      Inhibitory Concentrations of 66 commonly used drugs and determining the between
      assay variation of antimicrobial control standards. The modified method proved
      particularly sensitive for beta-lactams, tetracyclines, quinolones, marcrolides
      and lincosamides and least sensitive for anticoccidials and nitrofurans. The pH
      6.0 and 7.2 plates were more sensitive for 39 of the 66 antimicrobials (59%)
      whereas the two pH 8.0 plates (B. subtilis, M. luteus) were the most sensitive
      for 27 (41%). Muscle samples were taken from 1830 routine meat inspection
      investigations between 1994 and 1996. Of the 38 (2%) positive meat inspection
      carcasses, the following antimicrobials were confirmed above the MRL: penicillin
      G (10), oxytetracycline (16), sulphadimidine and sulphadiazine in combination (4)
      and chlortetracycline (1). The method as described is technically simple, cost
      effective, robust, suitable for large sample throughput and for frozen, thawed or
      fresh tissues. When all four plates are used the pattern of inhibition can reduce
      unnecessary confirmatory assays by indicating the antimicrobial group most likely
      to be present.

PMID- 10209576
TI  - Determination of fenthion and its oxidative metabolites in olives and olive oil:
      errors caused by matrix effects.
AB  - A method for determination of fenthion residues and its oxidative metabolites
      (fenoxon, fenthion sulphoxide, fenthion sulphone, fenoxon sulphoxide, fenoxon
      sulphone) in olive pulp, oil and water obtained from olive pressing is described
      and evaluated. Recoveries for the improved gas chromatographic conditions were:
      92-104% for fenthion, fenoxon, fenthion sulphone and fenoxon sulphone in the
      olive pulp matrix, whereas the mean recovery values for fenthion sulphoxide and
      fenoxon sulphoxide were respectively 140% and 118%. In the vegetation water
      matrix, the recoveries for fenthion, fenthion sulphoxide, fenoxon sulphoxide and
      fenoxon sulphone averaged between 91% and 103%. Higher values were obtained for
      fenoxon (139%) and for fenthion sulphone (115%). Recoveries for all metabolites
      in the oil matrix averaged between 100% and 104%. Detection limits ranged between
      0.005 ng for fenthion to 0.02 ng for fenoxon sulphoxide and fenoxon sulphone.
      Three different gas chromatographic conditions are presented in order to
      underline how their choice could strongly affect the result because of the matrix
      effect on the gas chromatographic response. In some cases such an effect can
      increase the instrumental response up to three times the real value.

PMID- 10209578
TI  - Fumonsin B1, B2, and B3 content of commercial unprocessed maize imported into
      South Africa from Argentina and the USA during 1992.
AB  - The widespread occurrence of F. moniliforme and the toxic effects of its
      secondary metabolites, the fumonisins B1(FB1), B2(FB2) and B3(FB3), make it
      imperative that fumonisin contamination of maize, a major constituent of animal
      feed as well as the staple diet of many populations, be closely monitored to
      reduce the risk of fumonisin exposure. Equine leukoencephalomalacia and porcine
      pulmonary oedema have been associated with the intake of feed heavily
      contaminated with fumonisins. In addition, high levels of fumonisins in the maize
      based staple diets of certain populations have been linked to a high incidence of
      oesophageal cancer in the Transkei region of South Africa and in Linxian and
      Cixian Counties, China. Bulk shipments of maize imported into South Africa from
      the USA and Argentina during 1992 were sampled at the port of entry to determine
      fumonisin levels. Of the 79 samples from two US shipments, all were positive for
      fumonisins, with FB1 constituting approximately 71% of the total fumonisins with
      an overall mean of 2.35 micrograms/gFB1. The maximum FB1 level observed was 3.9
      micrograms/g. These levels contrast with those obtained from two Argentinian bulk
      shipments, which also were all positive for fumonisins, but had a mean FB1 level
      of 0.31 microgram/g and a maximum observed level of 0.7 microgram/g FB1 measured
      over 47 composite samples.

PMID- 10209577
TI  - Mycotoxin production by Penicillium expansum on blackcurrant and cherry juice.
AB  - The production of mycotoxins and other secondary metabolites by Penicillium
      expansum on blackcurrant and cherry juice has been studied at 10 degrees C and 25
      degrees C under storage imitated conditions. P. expansum was able to synthesize
      extracellular patulin under all conditions, and together with extracellular
      chaetoglobosin A when unlimited oxygen was available. Patulin, the
      chaetoglobosins A and C, the communesins A and B and the expansolides A and B
      could be detected intracellularly depending on the conditions. The metabolites
      were detected using thin-layer chromatography and high-performance liquid
      chromatography with diode array detection by comparison to standards. A method to
      detect the expansolides A and B by TLC was developed.

PMID- 10209579
TI  - Comparison of isopropanol and isooctane as food simulants in plasticizer
      migration tests.
AB  - In the last 25 years, plastics have faced a massive demand in packaging
      technology due to their desirable properties, such as flexibility, light weight,
      etc. Moreover, their packaging applications have spread in the area of food and
      pharmaceutical products. Much concern has arisen from that fact as most of these
      plastics contain high amounts of additives which tend to migrate when they come
      into contact with liquid or solid surrounding media. Plasticized PVC is one of
      the most popular polymers in packaging technology and at the same time is subject
      to criticism for the high concentration levels of plasticizer in most of its
      applications. In an attempt to carry out simple and realistic migration tests,
      many investigators used simple organic substances which simulate as much as
      possible the behaviour of foods towards plasticizer migration. Much of our
      previous work intended to examine migration of dioctyl phthalate (DOP) from PVC
      sheets into some simple surrounding media, such as methanol, white spirit,
      paraffin oil, etc. The present work is focused on the examination of the
      plasticizer migration into two promising food simulants, namely isopropanol and
      isooctane. Radioactivity measurements were employed in order to detect
      quantitatively the plasticizer which had migrated into the surrounding liquid. In
      contrast to similar studies, the phenomenon of migration was studied until
      equilibrium was reached.

PMID- 10209580
TI  - Food and packaging interactions: determination of the kinetic parameters of olive
      oil diffusion in polypropylene using concentration profiles.
AB  - The penetration of olive oil into polypropylene was studied in order to allow a
      complete modellization of food and packaging interactions. Oil concentration
      profiles through polypropylene food trays were determined by FTIR-microscopy
      measurements along the thickness at various times. Calculations of the relevant
      parameters characterizing Fickian diffusion, namely constant diffusivity,
      coefficient of convective mass transport on the surface and concentration at
      equilibrium were carried out. This way of working has proven to be considerably
      shorter and more accurate than the method consisting of recording the global
      absorbance of the substance absorbed, especially when the amount of diffusing fat
      is low. Major conclusions are: that absorption of olive oil is strongly
      influenced by convection; the diffusion coefficient of olive oil in polypropylene
      is constant. Possible consequences to simplify global migration testing are
      discussed.

PMID- 10209581
TI  - Analysis of antioxidants extracted from polypropylene by supercritical fluid
      extraction.
AB  - Maximal potential migration of six antioxidants (AO) from five polypropylene (PP)
      formulations was determined by two supercritical fluid extraction (SFE)
      procedures, both of which contained static and dynamic steps. All analytical
      conditions affecting the extraction were studied and optimized using Irgafos 168
      as standard. SFE was more efficient as temperature and fluid density increased.
      During the static step in which the samples were exposed to the fluid without
      flux, the introduction of hexane and methanol as fluid modifiers significantly
      improved the extraction. Hexane appears to facilitate polymer swelling while
      methanol solvates the antioxidants. In the dynamic step (in which the extraction
      actually occurs) time is the key parameter. Extraction for 90 min results in an
      efficiency of around 75%. The introduction of modifiers during this step (by an
      HPLC-SFE procedure) did not produce any significant improvement. When SFE was
      carried out on all samples, extraction efficiency was around 75% except for
      Irganox 1010 and Hostanox O3. The large molecular volume of these antioxidants
      may be responsible for the considerable reduction of extraction efficiency.
      Particle size and shape of polymer sample were also important. The greater the
      surface to volume ratio the greater the extraction efficiency.

PMID- 10209582
TI  - Mobility of alpha-tocopherol and BHT in LDPE in contact with fatty food
      simulants.
AB  - The migration/sorption behaviour of butylated hydroxytoluene (BHT) and alpha
      tocopherol was studied in packaging material in contact with fatty food
      simulants. Two low-density polyethylene (LDPE) films, containing either BHT or
      alpha-tocopherol as antioxidants, were stored in contact with sunflower oil or
      95% (v/v) ethanol. The antioxidant content was monitored in the films throughout
      a period of 7 weeks. The migration of alpha-tocopherol into the food simulants
      was slower than that of BHT. Since alpha-tocopherol was transferred from the film
      to the simulant to a lesser extent, it is considered to be a more stable
      antioxidant than BHT when used in an LDPE film in contact with 95% ethanol or
      sunflower oil.

PMID- 10209583
TI  - Cytotoxicological safety assessment of papers and boards used for food packaging.
AB  - Because of the lack of information about the possible transfer of toxic compounds
      from papers and boards to food, the overall cytotoxicity induced by six papers
      and 15 boards was investigated from water extracts prepared according to the
      European prestandard. Cytotoxicity measurements were based on RNA synthesis rate
      of human HeLa S3 cells. The tested virgin and recycled papers and boards were
      differentiated and classified according to their cytotoxicological quality, which
      ranged from absence of any cytotoxic effect to severe inhibition of RNA synthesis
      rate. The cytotoxicity level also varied according to the total amount of
      compounds detected by gas chromatography. No correlation was found between
      cytotoxicity and endotoxins contained in the samples. No significant difference
      in cytotoxicity was observed between the papers and boards produced from virgin
      fibres and from recycled fibres. Moreover, the products obtained from chemical
      pulp showed lower cytotoxicity than the products based on mechanical pulp. More
      generally, the cytotoxicological approach is promising for monitoring paper/board
      treatment-induced problems. Further work is required to assess a modified
      standard procedure for the preparation of water extracts specifically adapted to
      paper/board.

PMID- 10209584
TI  - Supercritical fluid extraction (SFE) in food analysis: a review.

PMID- 10209585
TI  - Civilian parachute injuries; 10 years on and no lessons learned.
AB  - The Maidstone Hospital provides trauma services to one of the largest parachute
      clubs in the United Kingdom. We studied injuries sustained at the club in 1994
      and compared results with equivalent data from 1984. The injury rate for first
      time jumpers in the current study was 1.2%; half of these cases required
      admission for an average of 10 d. Individual morbidity and loss of productivity
      lasted far longer. No lessons had been learned from the first study. We question
      parachuting as a fund-raising venture and suggest re-evaluating the training of
      novice parachutists, perhaps with mandatory use of the safer rectangular
      parachute. At a time when healthcare rationing is an issue, individuals engaging
      in activities such as these might be required to indemnify themselves against the
      medical costs of injury currently met by the state.

PMID- 10209586
TI  - An evaluation of the Weber classification of ankle fractures.
AB  - This retrospective study over a 3 year follow-up was designed to establish the
      significance of the Weber classification of ankle fractures with regards to
      functional and radiographic outcome. One hundred and seven patients were
      available for follow-up, of which 88 ankles could be classified with the Weber
      system. Medial malleolar fractures alone and pilon fractures could not be
      classified with this system. A correlation was found between the type of Weber
      fracture and the overall ankle score. This held true for unimalleolar fractures
      alone. More complex bimalleolar and trimalleolar fractures did not follow this
      convention. Logistical regression analysis was used to evaluate other predictors
      of outcome. Bimalleolar and trimalleolar fractures were statistically significant
      predictors of a poorer outcome (P = 0.033, P = 0.021). The initial degree of
      displacement was also determined to be a predictor of outcome (P = 0.0133) as was
      the operative reduction (P = 0.0113). Using linear regression, older age (> 62
      years) was also established as a predictor of a poorer outcome (P < 0.05). The
      Weber classification was found to be a predictor of outcome in unimalleloar ankle
      fractures and not for multimalleolar fractures. We have identified further
      predictors of a poorer outcome in ankle fractures as the degree of initial
      injury, the number of malleoli fractured and older age. These factors were found
      to have greater significance in predicting outcome than the level of fibular
      fracture alone. We have identified a deficiency of the Weber system in excluding
      these criteria and have addressed this by modifying the existing system to
      include the number of malleoli involved, thus providing a more useful prognostic
      tool.

PMID- 10209587
TI  - Comparison of the results of short-term rigid and semi-rigid cast immobilization
      for the treatment of grade 3 inversion injuries of the ankle.
AB  - In this prospective, randomized study, short-term immobilization with semi-rigid
      (Soft Cast) and rigid (Scotchcast Plus) synthetic cast materials were compared
      for the functional treatment of acute grade 3 lateral ligament injuries of the
      ankle. Degree of ligament injury was assessed by clinical criteria. Duration of
      immobilization was 2 weeks for both groups and home physiotherapy was started
      thereafter. Fifty-seven patients completed the study and both materials were
      found to be equally effective in providing a stable ankle at the end of 6 weeks
      follow-up. Soft Cast group had better range of motion and could walk better at 2
      weeks, but these differences diminished at 6 weeks. With the Soft Cast, patient
      satisfaction was higher, need for a support for walking was less and return to
      work was earlier. When combined with the reduced cost of application, Soft Cast
      is the material of choice for the initial short-term immobilization for the
      functional treatment of acute ankle ligament injuries.

PMID- 10209588
TI  - Fractures of the hip: does the type of fall really affect the site of fracture?
AB  - The purpose of this study was to test accepted theories relating the
      characteristics of a fall to the anatomical site of hip fracture in the elderly.
      Twisting injuries are said to result in intracapsular fractures and falls
      directly onto the side are said to result in extracapsular fractures. 618
      consecutive patients with a hip fracture were studied prospectively by being
      questioned with regard to the nature of their fall. After exclusions, 552
      patients were left in the study. Of these, 324 patients sustained intracapsular
      fractures and 228 extracapsular fractures. More intracapsular fractures were
      associated with a fall onto the affected side than extracapsular fractures and
      rotation at the hip during the fall had a significant association with
      extracapsular fractures. In this study 84 per cent of all fractures occurred by
      falling directly onto the affected side. The clinical significance of this
      finding is that protective padding on the hip might be beneficial.

PMID- 10209589
TI  - Early active mobilisation of volar plate avulsion fractures.
AB  - This is a prospective follow up of 190 consecutive cases of volar plate avulsion
      fractures. A standard management regimen of immediate, active movement was
      followed in all cases and physiotherapy was rarely required. Of the 190 patients,
      162 were followed up for at least one year. An excellent or good outcome was
      achieved in 98 per cent. Patients presenting more than three weeks from injury
      had a worse outcome. The size and displacement of the avulsed fragment did not
      affect the outcome. For the stable joint, early active mobilisation with minimal
      or no splintage provides a good result.

PMID- 10209590
TI  - Results after operative treatment of intra-articular calcaneal fractures with a
      minimum follow-up of 2 years.
AB  - Thirty-one patients with 33 displaced intra-articular fractures of the calcaneus
      were treated with open reduction and internal fixation in our hospital between
      1989 and 1995. The fractures were classified according to the CT-classification
      of Crosby [Crosby, L. A. and Fitzgibbons, T., Computerized tomography scanning of
      acute intra-articular fractures of the calcaneus. The Journal of Bone and Joint
      Surgery, 1990, 72A, 852-859] and Hannover [Zwipp, H. and Tscherne, H. et al.,
      Osteosynthesis dislozierter intraartikularer calcaneusfrakturen. Unfallchirurg,
      1988, 91, 507-515]. The minimal follow-up was 2 years. Functional results were
      assessed at 6 and 12 months and in February 1997 using the Creighton calcaneal
      score. Overall results improved during follow-up, especially in the first year.
      At the final control the overall results were: excellent/good 73%, fair 21% and
      poor 6%. The results are comparable with larger series in the literature. The
      average range of motion in the subtalar joint was 65% of normal. No correlation
      was found between clinical outcome and the subtalar range of motion. Two patients
      received a secondary arthrodesis for painful arthrosis.

PMID- 10209591
TI  - The tension cord plaster: a method of immobilising the swollen elbow.
AB  - A method of immobilising the swollen elbow in a child is described. A length of
      traction cord is used to block extension, whilst a plaster backslab protects the
      point of the elbow. Constructive dressings in the cubital fossa may be avoided.
      This minimises the risk of further swelling and allows assessment of circulation
      in the elbow, forearm and hand without interfering with the integrity of the
      cast. Should increasing swelling threaten circulation, the traction cord may
      simply be cut on the ward to allow elbow extension. Use of this plaster is
      recommended when flexion of the elbow is necessary to maintain reduction of a
      fracture, such as following reduction of an extension-type supracondylar
      fracture.

PMID- 10209592
TI  - Hypothermia in critically ill trauma patients.
AB  - OBJECTIVE: To determine the incidence and mortality of hypothermia in trauma
      patients. METHODS: Retrospective review of patients admitted to the Surgical
      Intensive Care Unit (SICU) over 4 1/2 years. Hypothermia was defined as a
      temperature < 35 degrees C. RESULTS: There were 7045 admissions to the SICU, of
      which 661 (9.4%) had a recorded temperature of < 35 degrees C. Over half (395)
      were trauma patients, with a mortality of 52.7%. The temperature ranged from 27.1
      to 34.9 degrees C, with a mean for survivors of 34.0 degrees C and 33.1 degrees C
      for those that died. There was a significant difference in Apache II scores (16.6
      vs 25.4) and Injury Severity Scores (26.1 vs 33.4) between survivors and non
      survivors. CONCLUSIONS: The incidence of hypothermia in trauma patients is
      significant and is independent of the month of admission. Mortality is high but
      there is no threshold below which mortality is assured. Unlike historical data,
      13 patients survived temperatures < 32 degrees C.

PMID- 10209593
TI  - Long-term morbidity in patients suffering a sternal fracture following discharge
      from the A and E department.
AB  - OBJECTIVE: To describe the duration of symptoms and long term outcome in patients
      who were discharged home from the A and E department having sustained an isolated
      fracture of the sternum. DESIGN: Postal questionnaire. OUTCOME MEASURES: Patients
      were asked specific questions regarding advice and analgesia given on discharge,
      length of time off work, if appropriate, and length of time of symptoms related
      to the injury. RESULTS: A response rate of 55% was achieved. The majority of
      patients had been involved in a motor vehicle accident. Chest pain was the
      predominant persisting symptom lasting for a mean period of 10.9 weeks. Duration
      of symptoms was significantly prolonged in patients over the age of 50 (p <
      0.03). Although injury was more common in females this was not statistically
      significant (p < 0.09). Advice given regarding rehabilitation was poor and
      variable. CONCLUSION: Patients suffering a sternal fracture have prolonged
      symptoms. Those being discharged home from the A and E department are at present
      being given variable and poor advice. A more formal approach to rehabilitation,
      analgesia and a letter to the general practitioner outlining prognosis will
      improve their standard of care.

PMID- 10209594
TI  - Management of war penetrating craniocerebral injuries during the war in Croatia.
AB  - From September 1991 to December 1992, during the war in Croatia, the General
      Hospital in Slavonski Brod served as an evacuation centre. During that period 197
      patients with war-related penetrating craniocerebral injuries were admitted. They
      were analyzed according to wound characteristics, operability, mortality,
      operative and post-operative complications, and their condition after hospital
      discharge and follow-up. A less aggressive surgical approach was accepted in our
      surgical strategy, recommended in recent studies, followed by an aggressive
      intensive management. All patients received antibiotics ("war scheme") and
      anticonvulsants. Early results of treatment do not differ significantly from
      other recent studies (Vietnam, Israel) in respect to both mortality and
      complications. Follow-up was difficult. Most of the patients were Bosnia and
      Herzegovina citizens who were refugees and banished to foreign countries; thus
      their addresses were unknown. They are consequently lost to follow-up. A less
      aggressive surgical approach proved to be justified. Routine use of antibiotics
      and anticonvulsants lowered the infection rate and early seizure incidence to an
      acceptable level. Late seizure incidence is similar to those previously reported.

PMID- 10209595
TI  - Percutaneous fixation of Maisonneuve and Maisonneuve-type fractures: a minimally
      invasive approach.
AB  - We report five cases of Maisonneuve and Maisonneuve-type fractures which were
      treated with a single suprasyndesmotic percutaneous diastasis screw with good
      radiological and functional results. This is an effective and a minimally
      invasive procedure which we recommend.

PMID- 10209596
TI  - CT findings of sternal fracture.
AB  - A retrospective study of blunt chest injuries due to motor vehicle accidents
      between the years 1990 and 1995 found 9 cases of sternal fracture that had both
      lateral plain film and thoracic axial CT scans performed. Plain film identified 8
      of the 9 fractured sternums. CT scanning was only able to identify 6 sternal
      fractures. Secondary signs of sternal fracture were only seen in 5 of 9 patients,
      3 had retrosternal haematomas and 2 had haematoma of the mediastinum.
      CONCLUSIONS: (1) plain film is still superior to Axial CT scanning for
      identification of sternal fracture; (2) retrosternal haematoma, although a
      specific sign for sternal fracture has low sensitivity (3/9); (3) mediastinal
      haematoma, a poorly specific sign for sternal fracture also demonstrated low
      sensitivity.

PMID- 10209597
TI  - Cervical spine injuries sustained 'fly-jumping'.

PMID- 10209598
TI  - Colles fracture from air bag deployment.

PMID- 10209599
TI  - Avulsion fracture of the ischium.

PMID- 10209600
TI  - Greatly delayed complication of medial epicondyle injury.

PMID- 10209601
TI  - Septic arthritis due to Actinomyces pyogenes.

PMID- 10209603
TI  - Telephone-mediated lightning injury causing cataract.

PMID- 10209602
TI  - Acute exertional peroneal compartmental syndrome following prolonged horse
      riding.

PMID- 10209604
TI  - Traumatic apophyseal avulsion of the greater trochanter: case report and review
      of the literature.

PMID- 10209605
TI  - Inferior dislocation of the patella.

PMID- 10209606
TI  - The molecular and cell biology of allergy.

PMID- 10209607
TI  - Bones of contention. The supply of temporal bones for dissection: the legalities,
      problems and solutions.
AB  - Temporal bone dissection is considered to be an important aspect of the
      otological training of the Specialist Registrar with dissection skills being
      formally assessed in the Intercollegiate Fellowship Examination. However the
      procurement of cadaveric specimens suitable for dissection may be fraught with
      difficulties. The authors take an historical perspective to clarify the existing
      legal issues and outline the means available to improve supply.

PMID- 10209608
TI  - A simple reconstructive procedure for radiation-induced necrosis of the external
      auditory canal.
AB  - Localized necrosis of the bone, cartilage, and soft tissue of the external
      auditory canal is an uncommon side effect of radiotherapy to the parotid region.
      Five patients developed late onset skin necrosis of a quadrant of the ear canal
      secondary to an underlying osteoradionecrosis of the tympanic ring. We report a
      one-stage procedure to excise the necrotic tissue and replace it with a local
      rotational flap derived from the post-auricular skin. Otological side effects of
      radiotherapy are discussed.

PMID- 10209609
TI  - Tympanoplasty in children--a prospective study.
AB  - Considerable controversy surrounds the subject of tympanoplasty in children. This
      prospective study looked at the results of type-I tympanoplasty in children.
      Forty-five children in the age group of five to 14 years were selected for the
      study. All these cases had a central perforation without any evidence of
      cholesteatoma. The ear to be operated had to be dry for at least six weeks before
      surgery. Type I tympanoplasty was performed on these patients with autograft
      temporalis fascia by either the underlay or overlay technique. The overall
      success rates in 45 operations evaluated one year post-operatively was 91.1 per
      cent. The age of the patient had no influence on the success rate. The two
      factors which adversely influenced the success rate were the presence of near
      total perforation and bilateral perforations. It was concluded that type-I
      tympanoplasty has a good chance of success in children regardless of age.

PMID- 10209610
TI  - Long-term results of vestibular nerve section.
AB  - Records are available on 27 patients who had vestibular nerve section between
      1975 and 1987 giving a follow-up time of 10 to 22 years with a mean of 16 years.
      Episodic vertigo was fully controlled in 26 patients, one needing a
      labyrinthectomy 18 months later. In addition to the patient who had
      labyrinthectomy, one patient had immediate post-operative profound hearing loss
      so that long-term follow-up of hearing was possible in 25 patients. After six
      months there was an overall average improvement in hearing of 1 dB. Thereafter
      there were average deterioration of 7 dB at two years, 15 dB at 10 years, 23 dB
      at 15 years and 29 dB at 20 years. This deterioration was more marked in those
      who had better hearing at the time of surgery, with all 10 whose hearing was
      classified as good deteriorating to poor by 15 years. At 10 years hearing
      deteriorated by 25 dB in those with good hearing and by 7 dB in those with poor
      hearing. In 20 per cent of patients there was audiological evidence of eventual
      involvement of the other ear. Tinnitus became worse in five patients but was a
      major problem in only one patient. One patient suffered a facial paralysis with
      partial recovery and, in addition, in one the frontal branch was divided in the
      incision.

PMID- 10209611
TI  - Mechanisms in noise-induced permanent hearing loss: an evoked otoacoustic
      emission and auditory brainstem response study.
AB  - In this study 22 patients (44 ears) with noise-induced permanent hearing loss
      were audiologically evaluated using transient-evoked otoacoustic emissions
      (TEOAE) and auditory brain-stem response (ABR). Twenty-one normal subjects (42
      ears) without exposure to occupational noise were used as controls. Based upon
      the hearing loss at 4, 3, 2 and 1 kHz on the pure-tone audiogram, they were
      classified into four groups. In group 1 (eight ears), emissions were present in
      all ears but their TEOAE-noise level and their reproducibility (percentage)
      proved to be weak. The auditory brain-stem response (ABR) indicated that the I/V
      amplitude ratio, the latency values of wave V and the I-V intervals fell within
      the normal range in all ears. In Group 2 (14 ears), 40 per cent had no emissions,
      whereas the remaining ears showed weak emissions. The ABR revealed that in all
      ears the I/V amplitude ratio became small while wave V peak latency as well as I
      V intervals were within the normal range. In Group 3 (10 ears), emissions were
      absent in 50 per cent, while in the other ears the emissions were very weak. The
      ABR revealed that the I/V amplitude ratio, which could be calculated in the 60
      per cent in which wave I was present, was smaller than in Group 2. Wave V latency
      as well as I-V intervals were within the normal range. In Group 4 (12 ears), none
      of the ears showed emissions. The ABR indicated that the I/V amplitude ratio was
      much smaller when wave I was present (27 per cent) as well as I-V interval values
      being within the normal range. Wave V absolute latency value (delta V index)
      indicated a positive index in 17 per cent of this group (two ears) when wave I
      was absent. In the present study a dynamic process from cochlear outer hair cells
      to cochlear neurons was seen, correlating with an increasing hearing loss.

PMID- 10209612
TI  - Bacteriology of chronic purulent secretions in chronic rhinosinusitis.
AB  - The aim of this work was to study the bacterial flora of purulent secretions
      during chronic rhinosinusitis. We studied a total of 533 patients divided into
      two groups. The control population consisted of 139 adults (> 16 years) of both
      sexes seen in the community or hospitalized for less than 72 hours for non
      rhinological conditions. The rhinosinusitis group consisted of 394 patients
      referred to the ENT clinic with chronic rhinosinusitis. All the patients with
      rhinosinusitis had had a post-nasal discharge for at least three months,
      associated with purulent or mucopurulent secretions originating from the involved
      sinus cavity. All samples were obtained endonasally under endoscopic guidance
      from the sinus ostium or from the sinus cavity during surgery. Cultures were
      positive in 81.3 per cent of the control subjects and 83.1 per cent of the
      patients with rhinosinusitis. Corynebacteria, coagulase-negative staphylococci,
      propionibacteria and peptostreptococci were the main commensal organisms, while
      Haemophilus influenzae, streptococci, Streptococcus pneumoniae, Prevotella spp
      and Fusobacterium spp were probable causative pathogens. Anaerobes were isolated
      from approximately 25 per cent of the patients in the rhinosinusitis group.
      Betalactamase producers represented 27.5 per cent of H. influenzae and 28 per
      cent of Prevotella spp isolates. Diminished susceptibility to penicillin was
      found in 13 per cent of S. pneumoniae isolates. The amoxycillin-clavulanate
      combination was the most active oral antibiotic tested against the pathogenic
      species in vitro.

PMID- 10209613
TI  - Bone and temporal fascia graft for the closure of septal perforation.
AB  - OBJECTIVES: To assess the reliability of temporal fascia and bone graft for the
      closure of septal perforation. STUDY DESIGN: Prospective longitudinal non
      randomized. METHODS: The repair of septal perforation was performed using
      endonasal dissection; suture of the borders of the perforation on at least one
      side, and interposition of a graft of temporal fascia with bone, either a
      perpendicular plate of ethmoid (six) if available or mastoid cortex (three) if
      not. RESULTS: All patients had closure without re-perforation. Eight out of nine
      patients had complete closure of the perforation (88.8 per cent). These patients
      had perforations of less than 3 cm in diameter. The ninth patient had a
      perforation of more than 3 cm diameter (3.5 x 2.5 cm), and obtained a closure of
      about 80 per cent of the original perforation. The remaining perforation was in
      the posterior part of the nose. The patient was relieved of his symptoms
      (crusting and bleeding). This incomplete closure was most probably due to
      migration of the graft immediately after surgery. There was no morbidity of the
      donor site or the ear in the mastoid cortex graft group of patients. This is to
      our knowledge the first report of the use of the mastoid cortex as a graft in
      septal perforation. CONCLUSIONS: We consider that the graft of temporal fascia
      with bone is very reliable, and the use of bone ensures closure while avoiding
      the complications of a lax septum in large perforations. The technique is
      suitable for perforations up to 2.5 cm diameter. Perforations larger than 3 cm in
      diameter are more difficult to close, but closure of the anterior part of the
      perforation will relieve the patient from the most annoying symptoms.

PMID- 10209614
TI  - Thyroplasty for functional rehabilitation of the incompetent larynx.
AB  - Type I thyroplasty was performed in 12 patients with unilateral paralysis of the
      vocal fold. Subjective as well as objective improvement in vocal performance was
      reported in 11 patients. Aspiration was improved in six out of eight patients.
      Effort closure was evaluated by the ability of the patient to voluntarily raise
      his intra-abdominal pressure during Valsalva's manoeuvre. A comparison of pre-
      and post-thyroplasty measures, showed a statistically significant improvement in
      the efficacy of effort glottic closure (p < 0.05), indicating a better physical
      performance. We had one case of wound sepsis and another case of implant
      extrusion.

PMID- 10209616
TI  - An unusual case of otogenic pneumocephalus.
AB  - Otogenic pneumocephalus is a rare entity usually caused by temporal bone trauma.
      This paper describes a case of otogenic pneumocephalus of traumatic origin, in
      which the type of the fracture (a bony spicula was detached from the mastoid) and
      the location (Trautmann's triangle) were uncommon.

PMID- 10209615
TI  - Functional neck dissection: cure and functional results.
AB  - In this study, the cure and functional results of 133 functional neck dissections
      performed between 1992-1997 in Erciyes University Medical Faculty were evaluated.
      The overall recurrence rate was three per cent. This rate was 1.4 per cent for
      elective functional neck dissections and five per cent for curative functional
      neck dissections. Electromyographic studies showed that there was severe
      neurogenic deficit in the trapezius muscle of seven patients (12.5 per cent), and
      in the sternocleidomastoid muscle of 12 patients (21.4 per cent) among 56
      randomly selected patients. In all cases, the flow rate and diameter of the
      internal jugular vein was found to be normal by Doppler ultrasonography. The
      results of this study showed that functional neck dissection is a reliable
      technique for obtaining a high cure rate and functional results.

PMID- 10209617
TI  - A rare case of intramuscular haemangioma in a six-year-old boy--a diagnostic
      dilemma.
AB  - Intramuscular haemangiomas are uncommon tumours of the head and neck, occurring
      mainly in adults and usually located in the region of the masseter muscle and
      parotid gland. We report the case of a child with an intramuscular haemangioma
      over the left maxilla, which caused some diagnostic confusion in view of its
      atypical location combined with the unusual age and inflammatory mode of
      presentation.

PMID- 10209618
TI  - Primary mycobacterial infection of the uvula.
AB  - Tuberculosis, and non-tuberculous mycobacterial infections are becoming more
      common thus it is more likely that otolaryngologists will encounter these
      conditions. We describe an otherwise well patient, with symptoms and signs from
      chronic uvular inflammation, who proved to have a primary mycobacterial
      infection. This is an unique presentation in the literature and reminds
      clinicians of the need, where uncertainty exists in diagnosis, to consider
      mycobacterial infections.

PMID- 10209619
TI  - Infectious mononucleosis and bilateral peritonsillar abscesses resulting in
      airway obstruction.
AB  - Upper airway obstruction is an uncommon but recognized complication of infectious
      mononucleosis. The management depends upon the degree of airway compromise. In
      the case described, severe airway obstruction was treated by securing the airway
      with awake fibre-optic endoscopic intubation and then proceeding to
      tonsillectomy. Bilateral inferiorly loculated quinsies were encountered
      unexpectedly and drained. This is the first report of 'bilateral' quinsies,
      associated with infectious mononucleosis and severe airway obstruction. The
      association, pathogenesis and significance of this finding are also discussed.

PMID- 10209620
TI  - An unusual cause of obstructive sleep apnoea presenting during pregnancy.
AB  - We describe a case of lingual thyroid (LT) with primary hypothyroidism,
      presenting during pregnancy and continuing beyond it with oropharyngeal
      obstructive symptoms and sleep apnoea syndrome (SAS) of mixed type. Although SAS
      of a combined obstructive and central type should not be too surprising in a case
      of LT with hypothyroidism, we were unable to find such a documentation
      previously. Only four weeks of L-thyroxin treatment resulted in a dramatic
      improvement in dysphagia, disturbed phonation, haemoptysis, arterial
      desaturation, sleep apnoea and overall sleep efficiency, in conjunction with a
      regression in the size of the lingual mass. This case highlights the vagaries
      confronted in the management of such a case and focuses on efforts towards
      accurate diagnosis and treatment.

PMID- 10209621
TI  - Neonatal stridor in association with herpes simplex infection of the larynx.
AB  - Herpes simplex virus (HSV) infection in the neonatal period may be confined to
      the eyes, skin and upper aerodigestive tract or may be widely disseminated to
      other organs, with particular recognition of involvement of the central nervous
      system (CNS) causing herpes encephalitis (Whitley et al., 1980a, b; Andersen,
      1987). Primary laryngeal HSV infection is extremely uncommon. We present a case
      of acute neonatal stridor secondary to such localized disease and discuss its
      management.

PMID- 10209622
TI  - Myasthenia gravis presenting with dysphagia and postoperative ventilatory
      failure.
AB  - We report a case of myasthenia gravis presenting to the department of
      otolaryngology with acute dysphagia on two separate occasions over a one-year
      period. Diagnosis of myasthenia gravis was made when the patient developed
      ventilatory failure after his second general anaesthetic for rigid
      oesophagoscopy. Our patient required emergency transfer to the intensive therapy
      unit for ventilation. He improved after treatment with corticosteroids,
      anticholinesterase and immunosuppressive medications. Our case was unusual in
      that cricopharyngeal spasm causing dysphagia and significant aspiration was
      demonstrated by a barium swallow and this was completely resolved after treatment
      of the myasthenia gravis.

PMID- 10209623
TI  - Bilateral and multicystic major salivary gland disease: a rare presentation of
      primary Sjogren's syndrome.
AB  - We present a case of a 15-year-old girl with bilateral parotid and sub-mandibular
      salivary gland enlargement as the sole presentation of primary Sjogren's
      syndrome. The clinical, radiological, immunological and pathological features
      have been discussed. The relevant literature has been reviewed. To our knowledge
      this is the only reported case of Sjogren's syndrome presenting as multicystic
      disease with bilateral major salivary gland involvement.

PMID- 10209624
TI  - Intramuscular haemangioma of head and neck region.
AB  - Intramuscular haemangiomas are rare benign haemangiomas occurring within the
      skeletal muscle. These are uncommon tumours in the head and neck region and occur
      most frequently on the trunk and extremities. Fewer than 80 cases of intra
      muscular haemangioma in the head and neck region have been reported in the
      literature. A case of intramuscular haemangioma of the sternocleidomastoid muscle
      is presented. The review of occurrence and natural history of such tumours is
      described and clinical and radiological presentation, histological
      classifications and treatment modalities are discussed.

PMID- 10209625
TI  - Transorbital penetrating injury of the paranasal sinuses.
AB  - Penetrating injuries of the paranasal sinuses due to foreign bodies are rare,
      especially as a result of a traffic accident. Here we report a patient with a
      ballpoint pen lodged in his left eye following a traffic accident. The pen
      extended from the medial aspect of the left orbit, through the left ethmoid sinus
      and the nasal septum, to the right sphenoid sinus. We removed the pen
      uneventfully using endoscopic sinus surgery. There are no similar reports in the
      English literature and we therefore present this case because of its rarity.

PMID- 10209626
TI  - Fibrous histiocytoma of the larynx.
AB  - We present a case of fibrous histiocytoma of the larynx in a young female who
      presented eight years ago and is still alive and well with no evidence of any
      regional invasion or distant metastasis. This rare lesion has been described in
      30 cases previously of which 26 were malignant and four benign. Our case is
      unusual in a sense that histologically it has not been possible to determine its
      exact biological behaviour and growth potential. However, clinically it behaved
      as a low-grade malignant tumour.

PMID- 10209627
TI  - Verrucous carcinoma of the maxillary antrum.

PMID- 10209628
TI  - Oro-nasal transfer of nasogastric tube following endoscopic placement.

PMID- 10209629
TI  - A prospective evaluation of the feasibility of day-case microlaryngeal surgery.

PMID- 10209630
TI  - European Consensus Statement on Neonatal Hearing Screening.

PMID- 10209631
TI  - Cerebral predictions.

PMID- 10209632
TI  - Single units and visual cortical organization.
AB  - The visual system has a parallel and hierarchical organization, evident at every
      stage from the retina onwards. Although the general benefits of parallel and
      hierarchical organization in the visual system are easily understood, it has not
      been easy to discern the function of the visual cortical modules. I explore the
      view that striate cortex segregates information about different attributes of the
      image, and dispatches it for analysis to different extrastriate areas. I argue
      that visual cortex does not undertake multiple relatively independent analyses of
      the image from which it assembles a unified representation that can be
      interrogated about the what and where of the world. Instead, occipital cortex is
      organized so that perceptually relevant information can be recovered at every
      level in the hierarchy, that information used in making decisions at one level is
      not passed on to the next level, and, with one rather special exception (area
      MT), through all stages of analysis all dimensions of the image remain intimately
      coupled in a retinotopic map. I then offer some explicit suggestions about the
      analyses undertaken by visual areas in occipital cortex, and conclude by
      examining some objections to the proposals.

PMID- 10209633
TI  - Apparent depth with retinal image motion of expansion and contraction yoked to
      head movement.
AB  - The two main questions addressed in this study were (a) what effect does yoking
      the relative expansion and contraction (EC) of retinal images to forward and
      backward head movements have on the resultant magnitude and stability of
      perceived depth, and (b) how does this relative EC image motion interact with the
      depth cues of motion parallax? Relative EC image motion was produced by moving a
      small CCD camera toward and away from the stimulus, two random-dot surfaces
      separated in depth, in synchrony with the observers' forward and backward head
      movements. Observers viewed the stimuli monocularly, on a helmet-mounted display,
      while moving their heads at various velocities, including zero velocity. The
      results showed that (a) the magnitude of perceived depth was smaller with smaller
      head velocities (< 10 cm s-1), including the zero-head-velocity condition, than
      with a larger velocity (10 cm s-1), and (b) perceived depth, when motion parallax
      and the EC image motion cues were simultaneously presented, is equal to the
      greater of the two possible perceived depths produced from either of these two
      cues alone. The results suggested the role of nonvisual information of self
      motion on perceiving depth.

PMID- 10209634
TI  - Visual search of driving situations: danger and experience.
AB  - Previous research on visual search in driving suffers from a number of problems:
      small sample sizes, a concentration on mundane situations, and a failure to link
      results to more general psychological theory. The study reported in this paper
      addresses these issues by recording the eye movements of a large sample of
      drivers while they watched films of dangerous driving situations and comparing
      the findings with those from more general studies on scene perception. Stimuli
      were classified according to the types of road shown and the degree of danger
      present in the scenes. Two groups of subjects took part, fifty-one young novice
      drivers who had just gained a full driving licence and twenty-six older more
      experienced drivers. Dangerous situations were characterised by a narrowing of
      visual search, shown by an increase in fixation durations, a decrease in saccade
      angular distances, and a reduction in the variance of fixation locations. These
      effects are similar to the concept of 'attention focusing' in traumatic
      situations as it is described in the literature on eyewitness memory. When road
      types are compared, the least visually complex rural roads attracted the longest
      fixation durations and the shortest angular saccade distances, while the most
      visually complex urban roads attracted the greatest spread of search but the
      shortest fixation durations. Differences between the groups of subjects were also
      present. Novices had longer fixation durations than experienced drivers,
      particularly in dangerous situations. Experienced drivers also fixated lower down
      and had less vertical variance in fixation locations than novices.

PMID- 10209635
TI  - Effects of pattern orientation and number of symmetry axes on the detection of
      mirror symmetry in dot and solid patterns.
AB  - It has been postulated that as the number of axes of symmetry in a pattern
      increases, so pattern 'goodness' increases. Recently, a distinction was made
      between two different theoretical accounts of regularity or 'goodness' in
      relation to patterns with mirror symmetry: the 'transformational' and the
      'holographic' models. It was argued that the former predicts a 'goodness'
      ordering of four > three > two > one whereas the latter predicts four > two >
      three > one, where '>' means greater regularity or goodness. In three
      experiments, we have tested these predictions. In experiment 1, we measured
      percentage correct and reaction time to dot patterns which had one, two, three,
      or four axes of symmetry and were flashed for 150 ms. Experiment 2 was identical
      except that patterns were presented for 2000 ms. In experiment 3, dot patterns
      were replaced by solid shapes which also had one, two, three, or four axes of
      symmetry. Although it was found that stimuli with four axes clearly allowed
      superior performance to that of stimuli with one axis, results obtained with
      stimuli with two and three axes were almost identical and in between those
      obtained with one and four axes. The data thus support the suggestion that extra
      axes add 'goodness' to symmetrical patterns but not in a monotonic fashion.

PMID- 10209636
TI  - Illusory volumes from conformation.
AB  - The purpose of this paper is to offer demonstrations of 'illusory volumes' in the
      spirit of the illusory flat surfaces described by Kanizsa. These demonstrations
      of illusory volumes exploit a new cue to the recovery of surface curvature from
      ambiguous images: conformation. In assuming conformation, the visual system
      assumes that the surface of a volume conforms to the curvature of its
      neighboring, underlying, or supporting surface, in the absence of image cues to
      the contrary. Demonstrations that exploit the assumption of conformation provide
      several insights into the nature of the inferential processing that underlies
      contour, surface, and volume formation. In particular, these demonstrations imply
      that the visual system does not calculate local surface curvature, illusory
      contours, or occlusion relationships before it analyzes global surface
      relationships.

PMID- 10209638
TI  - Flying a lead balloon.

PMID- 10209637
TI  - Haptic perception of texture gradients.
AB  - To pick up 3-D aspects of pictures is arguably the most difficult problem
      concerning tactile pictorial perception by the blind. The aim of the experiments
      reported was to examine the potential utility of texture gradients in this
      context. Since there is no theoretical basis for predicting absolute values of 3
      D properties from 2-D patterns read by the finger pads, the abilities of
      participants to perceive gradients lying between known maxima and minima were
      assessed. Experiment 1 involved blindfolded sighted participants making verbal
      magnitude estimations of texture-gradient magnitudes corresponding to plane
      surfaces at different slants. In experiment 2 the participants' task was to
      orient a surface at a slant corresponding to the texture gradients depicted
      tactually, and experiment 3 required early-blind participants to attempt the same
      task. The results revealed that participants can scale the magnitudes of texture
      gradients with high precision and that they can also accurately produce surface
      slants from depictions, providing the extreme conditions are clearly defined and
      there are opportunities for learning. Texture gradients appear as informative to
      the blind as they do to the sighted. To what extent these data can be generalised
      to other gradients and textures or to other projections of 3-D scenes remains to
      be investigated.

PMID- 10209640
TI  - Does segregation by colour/luminance facilitate the detection of structure-from
      motion in noise?
AB  - The aim in the experiments was to examine whether the detection of structure-from
      motion (SFM) in noise was facilitated when target and noise were segregated by
      colour and/or luminance polarity. The SFM target was a rotating 'V-shape'
      structure simulated with limited-lifetime Gaussian micropatterns and embedded in
      random-motion noise. Threshold levels of V-shape slant were measured for stimuli
      in which target and noise were segregated or unsegregated by colour/luminance,
      and under two conditions, with and without static form cues to the SFM target.
      The presence or absence of static form cues to the SFM target was manipulated by
      varying the relative numbers of micropatterns in target and noise. In the absence
      of static form cues, segregation of target and noise by colour and/or luminance
      polarity did not facilitate target detection, even when subjects knew which
      micropatterns belonged to the target. On the other hand, when static form cues
      were present, segregation improved performance. These results imply that SFM
      processing is 'form-cue invariant' except when the target form is immediately
      identifiable in the static view of the stimulus. The significance of the results
      for understanding the role of colour vision in breaking camouflage and in
      'grouping' is discussed.

PMID- 10209639
TI  - Evidence for global motion interactions between first-order and second-order
      stimuli.
AB  - Recent research indicates that the early stages of visual-motion analysis involve
      two parallel neural pathways, one conveying information from luminance-defined
      (first-order) image features, the other conveying information from texture
      defined (second-order) features. It is still not clear whether these two pathways
      converge during later stages of global motion integration. According to one
      account they remain segregated, and feed separate global analyses. In the
      alternative account, all responses feed a common stage of global analysis. Two
      perceptual phenomena are universally held to result from interactions between
      detector responses during global motion integration--direction repulsion and
      motion capture. We conducted two psychophysical experiments on these phenomena to
      test for segregation of first-order and second-order responses during
      integration. Stimuli contained two components, either two random-block patterns
      transparently drifting in different directions (repulsion measurements), or a
      drifting square-wave grating superimposed on an incoherent random-block pattern
      (capture measurements). Repulsion and capture effects were measured when both
      stimulus components were the same order, and when one component was first order
      and the other was second order. Both effects were obtained for all combinations
      of first-order and second-order patterns. Repulsion effects were stronger with
      first-order inducing patterns, and capture effects were stronger with second
      order inducers. The presence of perceptual interactions regardless of stimulus
      order strongly suggests that responses in first-order and second-order pathways
      interact during global motion analysis.

PMID- 10209641
TI  - A computational and perceptual account of motion lines.
AB  - To indicate motion in a static drawing, artists often include lines trailing a
      moving object. The use of these motion lines is notable because they do not seem
      to be related to anything in the optic array. The dynamic behavior of a neural
      network model for contour detection is analyzed and it is shown that it generates
      trails of oriented responses behind moving stimuli. The properties of the
      oriented response trails are shown to correspond to motion lines. The model
      generates trails of different orientations depending on the speed and length of
      the movement, and thereby predicts different uses of two types of motion lines.
      The model further predicts that motion lines should bias real motion in some
      situations. An experiment relating motion lines to ambiguous motion percepts
      demonstrates that motion lines contribute to motion percepts.

PMID- 10209642
TI  - Rigid objects that appear to bend.
AB  - Simple rigid objects are presented that appear to bend when viewed from certain
      angles. These illusions illustrate that perspective information is used by the
      stereo system, that projective distortions can override rigidity constraints in
      motion perception, and that touch only corrects the illusion for a local region.

PMID- 10209643
TI  - The analysis of orientation-dependent time costs in visual recognition.
AB  - How does the visual system recognise stimuli presented at different orientations?
      According to the multiple-views hypothesis, misoriented objects are matched to
      one of several orientation-specific representations of the same objects stored in
      long-term memory. Much of the evidence for this hypothesis comes from the
      observation of group mean orientation effects in recognition memory tasks showing
      that the time taken to identify objects increases as a function of the angular
      distance between the orientation of the stimulus and its nearest familiar
      orientation The aim in this paper is to examine the validity of this
      interpretation of group mean orientation effects. In particular, it is argued
      that analyses based on group performance averages that appear consistent with the
      multiple-views hypothesis may, under certain circumstances, obscure a different
      theoretically relevant underlying pattern of results. This problem is examined by
      using hypothetical data and through the detailed analysis of the results from an
      experiment based on a recognition memory task used in several previous studies.
      Although a pattern of results that is consistent with the multiple-views
      hypothesis was observed in both the group mean performance and the underlying
      data, it is argued that the potential limitations of analyses based solely on
      group performance averages must be considered in future studies that use
      orientation effects to make inferences about the kinds of shape representations
      that mediate visual recognition.

PMID- 10209644
TI  - Picturing peripheral acuity.
AB  - The grain of the retina becomes progressively coarser from the fovea to the
      periphery. This is caused by the decreasing number of retinal receptive fields
      and decreasing amount of cortex devoted to each degree of visual field (=
      cortical magnification factor) as one goes into the periphery. We simulate this
      with a picture that is progressively blurred towards its edges; when strictly
      fixated at its centre looks equally sharp all over.

PMID- 10209645
TI  - Relative spatial expansion and contraction within the Muller-Lyer and Judd
      illusions.
AB  - The shaft portions of Muller-Lyer (M-L) figures, one-ended M-L figures, Judd
      figures, and their respective control (tails-up) figures were divided by subjects
      into eight equal-appearing intervals by means of successive bisections. For most
      of the control stimuli the length of the left half of the shaft tended to be
      overestimated relative to the length of the right side. For the tails-out version
      of the M-L figure, there was relative overestimation of segments of the shaft
      adjacent to the tails, while for the tails-in version there was relative
      underestimation of these segments. These results indicate that the distortion of
      perceived length in the M-L illusion is not distributed evenly along the shaft.
      For the one-ended M-L figures the apparent overestimations and underestimations
      extended further along the shaft than for the standard figures. For the Judd
      figure perceived length varied systematically along the length of the shaft from
      underestimation near the tails-in end of the figure to overestimation near the
      tails-out end. These results are contradictory to the hypothesis that the M-L
      illusion results from inappropriate size scaling produced through the operation
      of size-constancy mechanisms, since this conjecture would predict uniform
      expansion or contraction. The results are compared with findings that
      localization responses are accurate for M-L figures but biased for one-ended M-L
      figures and Judd figures.

PMID- 10209646
TI  - Assimilation of achromatic color cannot explain the brightness effects in the
      achromatic neon effect.
AB  - If the mouths of the pacmen of a Kanizsa square are colored, for example red,
      then an illusory red transparent square is seen. In many visual theories such
      'neon color spreading' is explained by assimilation of chromatic and achromatic
      color. In this paper the achromatic case was investigated. In a two-alternative
      forced-choice task thirty observers judged the brightness of achromatic neon
      figures. The results suggest that assimilation of achromatic color inside and/or
      outside of the illusory figures cannot explain the brightness effects seen in
      achromatic neon color spreading. Although these displays may produce
      assimilation, it appears that contrast (perhaps acting nonlocally) is a stronger
      influence on their perceived brightness.

PMID- 10209647
TI  - The luminance conditions of Fuchs's transparency in two-dimensional patterns.
AB  - Fuchs's transparency occurs when the contour of a transparent surface encloses
      the contour of another surface located on an underlying homogeneous background.
      The luminance conditions of Fuchs's transparency have not yet been determined.
      Six experiments were designed to study this problem with achromatic two
      dimensional patterns. An ellipse enclosing a coplanar square was briefly
      presented. It simulated the cast of an elliptical spotlight or shadow on the
      square. The duration of the ellipse, the luminance of the square before the
      ellipse appeared, and the luminance of two squares outside the ellipse did not
      substantially affect the probability of perceiving the ellipse as transparent.
      However, this probability varied largely with the single values of the stimulus
      luminance differences and with the order relations of the stimulus luminances. It
      is concluded that this local and global luminance information conditioned the
      occurrence of Fuchs's transparency in two-dimensional patterns.

PMID- 10209648
TI  - Hens use occlusion to judge depth in a two-dimensional picture.
AB  - Hens (Gallus gallus domesticus) were taught to peck at a touch screen. On the
      screen was a grid on which a square and a circle were depicted. The square and
      the circle were given different positions at random for each trial, but were
      never overlapping. The hens were rewarded for pecking at the symbol that was
      higher up on the grid/screen, i.e. at the one that to a human observer was seen
      as being further away. Every tenth trial was a probe trial in which the animals
      were presented with either the circle overlapping the square or vice versa. The
      hens were never rewarded during the probe trials. As mentioned, the hens had
      learned to peck at the symbol that appeared to be further away during the
      nonprobe trials. During the probe trials the hens pecked at the symbol that was
      occluded, i.e. in the absence of any other cues they used occlusion to determine
      which of the two symbols was further away. The results suggest that not only can
      nonhuman animals use image height as a cue but that they can generalise this to
      situations in which occlusion is the only depth cue present.

PMID- 10209649
TI  - The influence of stimulus tilt on haptic curvature matching and discrimination by
      dynamic touch.
AB  - We investigated whether haptic comparison of the curvature of strips is
      influenced by the tilt (the average slope relative to the horizontal) of the
      curved strips. This particular stimulus manipulation was chosen to decide between
      two broad ways in which dynamic curvature comparison might be done: on the basis
      of the attitude (slope) differences over the surfaces or on the basis of the
      attitude (slope) differences between successively presented surfaces. For this
      purpose we conducted matching and discrimination experiments in which strips of
      constant curvature 9 cm long were touched dynamically and the tilts of the strips
      were varied. The results of the matching experiment showed some influence of
      tilt: the strips were judged to be slightly more curved if the tilt was nonzero
      than if it was zero. The results of the discrimination experiment did not show an
      effect of tilt. Because the attitude (slope) differences over the surfaces were
      independent of the tilt it is concluded that curvature comparison is based
      primarily on attitude differences over the curved surfaces.

PMID- 10209650
TI  - Movements towards tailor-made fats.

PMID- 10209651
TI  - Fatty acid ethyl esters: ethanol metabolites which mediate ethanol-induced organ
      damage and serve as markers of ethanol intake.

PMID- 10209652
TI  - Recent developments in biochemistry of the plant lipoxygenase pathway.

PMID- 10209653
TI  - Lipoprotein and cholesterol metabolism in diet-induced coronary artery
      atherosclerosis in primates. Role of cholesterol and fatty acids.

PMID- 10209654
TI  - Lipid trafficking in plant cells.

PMID- 10209655
TI  - Receptor-mediated mechanisms of lipoprotein remnant catabolism.
AB  - Chylomicron and VLDL are triglyceride-rich lipoprotein particles assembled by the
      intestine and liver respectively. These particles are not metabolized by the
      liver in their native form. However, upon entry into the plasma, their
      triglyceride component is rapidly hydrolyzed by lipoprotein lipase and they are
      converted to cholesterol-rich remnant particles. The remnant particles are
      recognized by the liver and rapidly cleared from the plasma. This process is
      believed to occur in two steps. (i) An initial sequestration of remnant particles
      on hepatic cell surface proteoglycans, and (ii) receptor-mediated endocytosis of
      remnants by hepatic parenchymal cells. The initial binding to proteoglycans may
      be facilitated by lipoprotein lipase and hepatic lipase which possess both lipid-
      and heparin-binding domains. The subsequent endocytic process may be mediated by
      LDL receptors and/or LRP. Both receptors have a high affinity for apoE, a major
      apolipoprotein component of remnant particles. The lipases may also serve as
      ligands for these receptors. An impairment of any component of this complex
      process may result in an accumulation of remnant particles in the plasma leading
      to atherosclerosis and coronary heart disease.

PMID- 10209656
TI  - What should we do about blood pressure and stroke?

PMID- 10209657
TI  - The role of factor XIIIVal34Leu in cardiovascular disease.

PMID- 10209658
TI  - Fatty liver--an additional and treatable feature of the insulin resistance
      syndrome.
AB  - To test the hypothesis that fatty liver coexists with other metabolic
      abnormalities of the insulin resistance syndrome, and responds to their
      amelioration, we prospectively studied 48 consecutive patients with chronically
      elevated liver enzymes and clinical, ultrasound and histological findings
      consistent with fatty infiltration of the liver. Most of the patients were
      overweight or obese (64%) with increased waist circumference which closely
      relates to visceral fat. Only 10% of the patients had normal glucose tolerance:
      44% had diabetes mellitus, 29% impaired glucose tolerance, and 17% were
      hyperinsulinaemic. The most common dyslipidaemia found was hypertriglyceridaemia
      and/or low HDL-C (86%). Dietary intervention and follow-up (median 24 months),
      supplemented by oral hypoglycaemic or lipid-lowering drugs as needed, resulted
      not only in weight loss (mean 3.7 kg), decreased fasting blood glucose (p <
      0.005) and improvement in serum lipid profile (p < 0.02 for both triglycerides or
      HDL-C) but also in an improvement of serum liver enzymes in 96%, which became
      normal in more than half of the patients. Thus, fatty liver was strongly
      associated with many features of the insulin resistance syndrome, and follow-up
      revealed a high potential for reversibility and a benign course.

PMID- 10209659
TI  - Group psychological treatment for chest pain with normal coronary arteries.
AB  - We used a psychological treatment package (education, relaxation, breathing
      training, graded exposure to activity and exercise, and challenging automatic
      thoughts about heart disease) to treat 60 patients who had continuing chest pain
      despite cardiological reassurance following haemodynamically normal angiography.
      The treatment was delivered in six sessions over eight weeks to groups of up to
      six patients. The patients kept daily records of chest pain episode frequency and
      nitrate use. Questionnaires were used to assess anxiety, depression and
      disability. Exercise tolerance was tested by treadmill electrocardiography, with
      capnographic assessment of hyperventilation. The results were compared with
      waiting-list controls. Treatment significantly reduced chest pain episodes (p <
      0.01) from median 6.5 to 2.5 per week. There were significant improvements in
      anxiety and depression scores (p < 0.05), disability rating (p < 0.0001) and
      exercise tolerance (p < 0.05), and these were maintained at six month follow-up.
      Treatment reduced the prevalence of hyperventilation from 54% to 34% (p < 0.01)
      but not the prevalence of ECG-positive exercise tests. Patients continuing to
      attribute their pain to heart disease had poorer outcomes. Group psychological
      treatment for non-cardiac chest pain is feasible, reduces pain, psychological
      morbidity and disability, and improves exercise tolerance.

PMID- 10209660
TI  - Patient-related outcomes five years after coronary artery bypass graft surgery.
AB  - For five years, we prospectively studied 353 consecutive patients undergoing
      first-time coronary artery bypass graft surgery (CABG) for stable angina in the
      North of England. Angina was present before surgery in nearly all patients, in
      20% 3 months after surgery, and in 48% after 60 months. The Nottingham Health
      Profile, showed a significant improvement in perceived health status (PHS) 12 and
      60 months after surgery compared with preoperation. However, PHS at 60 months was
      worse than at 12 months in the dimensions 'pain' and 'physical mobility' in part
      1, and in 'looking after the home' and 'taking holidays' in part 2. Employment
      rates were 36%, 34% and 21%, before, and 12 and 60 months after surgery,
      respectively. Working at 12 and 60 months was associated with age below
      retirement age, work preoperation and absence of angina, and at 12 months also
      with male gender and waiting time < 6 months. This study describes everyday
      clinical practice. The significant improvement in angina symptoms and PHS after
      CABG persists for at least 5 years. However, only one third of patients in this
      geographical area return to work, and this is not solely dependent on clinical
      symptoms.

PMID- 10209661
TI  - Cardiovascular autonomic nervous system dysfunction in patients with rheumatoid
      arthritis and systemic lupus erythematosus.
AB  - Although peripheral and central nervous system involvement have been well
      recognized in patients with rheumatoid arthritis (RA) and systemic lupus
      erythematosus (SLE), autonomic nervous system (ANS) involvement has rarely been
      studied, and has shown conflicting results. We performed cardiovascular ANS
      assessment in 34 RA and 37 SLE patients, using standard cardiovascular reflex
      tests. The results in each patient were compared with age- and sex-matched
      healthy controls. Forty-seven percent of the RA patients and 19% of the SLE
      patients had symptoms suggesting ANS dysfunction. The heart rate variation in
      response to deep breathing was significantly decreased in both the RA and SLE
      patients (p = 0.001). This diminished heart rate response showed no correlation
      with the disease duration, the number of swollen joints, the Ritchie articular
      index, ESR, or rheumatoid factor in the RA group, or the disease duration, the
      SLEDAI score or ESR in the SLE group. The clinical significance of the diminished
      cardiovascular ANS response needs to be investigated.

PMID- 10209662
TI  - Central nervous system sarcoidosis--diagnosis and management.
AB  - A series of 68 patients with neurosarcoidosis is reported, with particular
      emphasis on clinical aspects, diagnosis and treatment. A classification system
      based on clinical diagnostic probability is proposed, consisting of probable and
      definite disease, the latter being dependent on finding sarcoid granulomas on
      nervous system histology, which was obtained in 12 patients (18%). The role of
      investigations, including magnetic resonance imaging (MRI), chest radiography,
      Kveim skin test, Gallium 67 isotope scanning and cerebrospinal fluid (CSF)
      studies, is considered. Sixty-two percent of patients presented with nervous
      system disease, most commonly affecting the optic nerve and chiasm. Other common
      presentations included cranial nerve palsies, spinal cord and brainstem
      manifestations. Investigations yielding most diagnostic information included the
      Kveim test (41/48, 85% positive), raised CSF protein and/or cells (50/62, 81%)
      and gallium 67 scan (14/31, 45%). Eleven out of 29 patients (38%) patients showed
      meningeal enhancement on MRI scanning and 43% of scans demonstrated multiple
      white-matter lesions. Mean follow-up for the group was 4.6 years. Forty-seven
      patients were seen for > 18 months, and over half of these patients progressed
      despite corticosteroid and other immunosuppressive therapies. The benefit of a
      large patient database prospectively studied, with extended follow-up is
      discussed in order to learn more about prognosis and advance therapy in
      neurosarcoidosis.

PMID- 10209663
TI  - Is gliadin mispresented to the immune system in coeliac disease? A hypothesis.
AB  - The primary pathogenic trigger in coeliac disease (CD) is still unknown. We
      present the hypothesis that in CD the enterocytes could metabolize gliadin
      through an immunogenic pathway instead of a tolerogenic one. The result of this
      abnormal presentation of gliadin to the immune system would be the activation of
      lamina propria T cells, followed by the onset of enteropathy.

PMID- 10209664
TI  - Dissecting intramural haematoma of the oesophagus exacerbated by heparin therapy.

PMID- 10209665
TI  - Peptides as drugs.

PMID- 10209666
TI  - Genetic predisposition to gastric cancer.

PMID- 10209667
TI  - Treatment of myeloma.
AB  - Survival for myeloma has improved from a median of 7 months in the 1950s to about
      30 months today. Progress in chemotherapy has contributed a great deal to this
      improvement, although it may also, in part, reflect the improved treatment of
      infections, renal failure and hypercalcaemia as well as earlier diagnosis. For
      over 30 years, the gold standard of treatment has been oral melphalan and
      prednisolone, producing a clinical response in approximately 60% of patients and
      a median survival of around 36 months. Relapse is unfortunately inevitable in all
      but a handful and, for the majority, treatment can only hope to produce
      significant periods of remission with minimal treatment-related morbidity and
      mortality. Recently, improved results have been seen with the introduction of
      aggressive chemotherapy and bone-marrow transplantation. Marrow ablative
      therapies produce remissions in virtually all patients, with complete remissions
      in approximately 1/3. The best response is seen in those with a lower tumour
      burden, which will reduce the development of secondary resistance. Current
      treatment is moving towards an approach using sequential therapy. This involves
      induction chemotherapy with VAD or a similar regimen such as VAMP (vincristine,
      adriamycin and methylprednisolone), proceeding to high-dose therapy, often with
      some form of stem-cell rescue. This ensures minimal tumour burden prior to high
      dose treatment as well as reducing graft infiltration, improving general
      performance status and allowing recovery of renal function. Relapse remains a
      problem, although the use of IFN may reduce this by prolonging the plateau phase.
      High-dose therapy should be given early, before prolonged use of alkylating
      agents induces stem-cell dysplasia, before significant complications arise from
      the myeloma, and before drug resistance is significant. Unfortunately, these
      treatments come at a price, in terms of increased treatment-related toxicity.
      There also remains uncertainty as to the extra benefits of high-dose treatment
      with marrow rescue over high-dose chemotherapy alone. We await the current MRC
      trial with interest. For a very few, there is the tantalising possibility of cure
      with allografting. For those in complete remission after first-line induction
      therapy, allogeneic bone-marrow transplantation offers the best hope of survival,
      but comes at a greatly increased risk of toxicity, and it is uncertain if it is
      superior to autografting for the majority of patients. It may soon be possible to
      identify those poor prognosis patients in whom an allogeneic transplant should be
      offered at an early stage. Candidate biochemical markers include serum beta 2
      microglobulin, neopterin, IL-6, plasma cell labelling index, CRP or LDH and
      prognostic clinical features include IgD myeloma or stage III disease at
      presentation. Many patients will have primary refractory of relapsing disease in
      whom survival is short despite all current therapeutic modalities. They should
      therefore be considered for trials of newer agents, drug combinations and
      therapeutic interventions such as cytokine manipulation or gene therapy. The lack
      of effective, curative treatment options for patients with myeloma places great
      importance on effective palliation. While improving survival duration remains
      elusive in this condition, all possible efforts must be made to ensure quality of
      life is maximized.

PMID- 10209668
TI  - The misdiagnosis of epilepsy and the management of refractory epilepsy in a
      specialist clinic.
AB  - We assessed the frequency, causes and consequences of erroneous diagnosis of
      epilepsy, and the outcome of patients referred with 'refractory epilepsy', by
      retrospective analysis of the case records of 324 patients. The sample was
      divided into those exposed to anti-epileptic drugs (n = 184), of whom 92 were
      said to have refractory seizures, and those who had not received treatment (n =
      140). The latter group is reported elsewhere. The overall misdiagnosis rate was
      26.1% (46/184), with incomplete history-taking and misinterpretation of the EEG
      equally responsible. Side-effects were reported by 19/40, while unnecessary
      driving restrictions and employment difficulties were encountered by 12/33 and
      5/33, respectively. Of those labelled 'refractory epilepsy', 12 did not have
      epilepsy. Sixteen were rendered seizure-free and 25 significantly improved by the
      optimal use of anti-epileptic drugs or surgery. Diagnostic and management
      services for patients with suspected and established epilepsy are suboptimal,
      with psychological and socio-economic consequences for individual patients. The
      resulting economic burden on the health and welfare services is probably
      substantial.

PMID- 10209669
TI  - Prevalence of hepatitis C in prisons: WASH-C surveillance linked to self-reported
      risk behaviours.
AB  - We used cross-sectional willing anonymous salivary hepatitis C (WASH-C)
      surveillance linked to self-completed risk-factor questionnaires to estimate the
      prevalence of salivary hepatitis C antibodies (HepCAbS) in five Scottish prisons
      from 1994 to 1996. Of 2121 available inmates, 1864 (88%) participated and
      1532/1864 (82%) stored samples were suitable for testing. Overall 311/1532
      (20.3%, prevalence 95% CI 18.3-22.3%) were HepCAbS-positive: 265/536 (49%, 95% CI
      45-54%) injector-inmates but only 27/899 (3%, 95% CI 2-4%) non-injector-inmates.
      Among injectors, HepCAbS positivity was only slightly higher (p = 0.03) in those
      who had injected inside prison (53%, 162/305) than in those who had not (44%,
      98/224). Those who began injecting in 1992-96 were much less likely to be HepCAbS
      positive than those who started pre-1992 (31%, 35/114 vs. 55%, 230/422; p <
      0.001). Even with injectors who began in 1992-96 but had never injected inside
      prison, the prevalence of hepatitis C carriage was 17/63 (95% CI 16-38%). The
      prevalence and potential transmissibility of hepatitis C in injector-inmates are
      both high. Promoting 'off injecting' before 'off drugs' (both inside and outside
      prison), methadone prescription during short incarcerations, alternatives to
      prison, and support of HepCAbS-positive inmates in becoming eligible for
      treatment, all warrant urgent consideration.

PMID- 10209670
TI  - Age-independent oxidative stress in elderly patients with non-insulin-dependent
      diabetes mellitus.
AB  - Impaired antioxidant defence is implicated in the development of cardiovascular
      complications in non-insulin-dependent diabetes (NIDDM). However, as many of
      these patients are elderly, observed changes in antioxidant status may be due to
      the patient's age rather than their disease. We sampled blood from 47 elderly
      NIDDM patients (21 male and 26 female; mean age +/- SD, 75.62 +/- 7.97 years), 66
      young (30 male and 36 female; 24.52 +/- 4.72 years) and 58 healthy elderly
      volunteers (17 male and 41 female; 70.74 +/- 4.85 years), and measured the
      antioxidant glutathione, the marker for free-radical-damage lipid hydroperoxide
      products (LHP), vitamin E and total antioxidant capacity (TAC). There was a
      significant increase in LHP in the healthy elderly group compared with the young
      volunteers (3.14 +/- 1.5 vs. 2.14 +/- 1.38 mumol/l, p < 0.01). The values were
      much higher in NIDDM patients (7.02 +/- 2.29 mumol/l, p < 0.0001 vs. healthy
      elderly). There was a reduction in TAC in healthy elderly compared with the young
      (359.99 +/- 54.82 vs. 471.47 +/- 94.29 mumol/l trolox equivalents, p < 0.0001),
      but there was no further reduction in NIDDM patients. Similarly, glutathione was
      reduced to the same degree in healthy elderly and NIDDM patients (0.29 +/- 0.09,
      0.30 +/- 0.11 vs. 0.54 +/- 0.19 mumol/l in young volunteers, p < 0.0001). Vitamin
      E concentrations were comparable in all groups (26.34 +/- 5.39 young volunteers,
      31.50 +/- 8.23 healthy elderly and 30.98 +/- 9.03 mumol/l NIDDM patients), but
      after correction for serum cholesterol there was a significant reduction in the
      diabetic group compared with the young, but not with the elderly (5.54 +/- 1.55
      vs. 6.67 +/- 1.86 vs. 6.31 +/- 1.85 (mumol/l)/(mmol/l), p < 0.01). We have
      demonstrated an age-dependent reduction in total antioxidant capacity and
      glutathione defence and an age-independent increase in LHP in elderly patients
      with NIDDM. Reduced concentrations of vitamin E were demonstrated in NIDDM
      patients compared with young, but not elderly, volunteers. Increased oxidative
      damage occurs independently of age in NIDDM patients despite comparable
      antioxidant defences in this age group.

PMID- 10209671
TI  - Plasma chain-breaking antioxidants in Alzheimer's disease, vascular dementia and
      Parkinson's disease.
AB  - We studied the plasma chain-breaking antioxidants alpha carotene, beta carotene,
      lycopene, Vitamin A, Vitamin C, Vitamin E and a measure of total antioxidant
      capacity, TAC, in 79 patients with Alzheimer's disease (AD), 37 patients with
      vascular dementia (VaD), 18 patients with Parkinson's disease and dementia
      (PDem), and 58 matching controls, together with 41 patients with Parkinson's
      disease (PD) and 41 matching controls. Significant reductions in individual
      antioxidants were observed in all dementia groups. When compared to controls, the
      following were reduced: Vitamin A in AD (p < 0.01) and VaD (p < 0.001); Vitamin C
      in AD (p < 0.001), VaD (p < 0.001) and PDem (p < 0.01); Vitamin E in AD (p <
      0.01) and VaD (p < 0.001); beta carotene in VaD (p = 0.01); lycopene in PDem (p <
      0.001). Lycopene was also reduced in PDem compared to AD (p < 0.001) and VaD (p <
      0.001). Antioxidant levels in PD were not depleted. No significant change in TAC
      was seen in any group. The reduction in plasma chain-breaking antioxidants in
      patients with dementia may reflect an increased free-radical activity, and a
      common role in cognitive impairment in these conditions. Increased free-radical
      activity in VaD and PDem could be associated with concomitant AD pathology.
      Individual antioxidant changes are not reflected in TAC.

PMID- 10209672
TI  - How should we pay doctors? A systematic review of salary payments and their
      effect on doctor behaviour.
AB  - We reviewed the published and unpublished international literature to determine
      the influence of salaried payment on doctor behaviour. We systematically searched
      Medline, BIDS Embase, Econlit and BIDS ISI and the reference lists of located
      papers to identify relevant empirical studies comparing salaried doctors with
      those paid by alternative methods. Only studies which reported objective outcomes
      and measures of the behaviour of doctors paid by salary compared to an
      alternative method were included in the review. Twenty-three papers were
      identified as meeting the selection criteria. Only one of the studies in this
      review reported a proxy for health status, but none examined whether salaried
      doctors differentiated between patients on the basis of health needs. Therefore,
      we were unable to draw conclusions on the likely impact of salaried payment on
      efficiency and equity. However, the limited evidence in our review does suggest
      that payment by salaries is associated with the lowest use of tests, and
      referrals compared with FFS and capitation. Salary payment is also associated
      with lower numbers of procedures per patient, lower throughput of patients per
      doctor, longer consultations, more preventive care and different patterns of
      consultation compared with FFS payment.

PMID- 10209673
TI  - Atheroma: links with antiphospholipid antibodies, Hughes syndrome and lupus.
AB  - Antiphospholipid antibodies (aPL) are found in a variety of autoimmune diseases,
      and are thought to predispose to arterial and venous thrombosis. These
      antibodies, when investigated in different assays in vitro, activate endothelial
      cells and promote uptake of modified LDL to macrophages. These observations
      suggest that aPL can contribute to atheroma development by targeting some of the
      sequential steps that constitute early atherogenesis. If substantiated by large
      scale clinical trials, the pro-atherogenic properties of aPL may merit screening
      and intervention programs in selected populations.

PMID- 10209674
TI  - Anonymous survey of blood donors by polymerase chain reaction for Tropheryma
      whippelii.

PMID- 10209675
TI  - Mycobacterial promoters.

PMID- 10209676
TI  - Conservation of IS6110 sequence in strains of Mycobacterium tuberculosis with
      single and multiple copies.
AB  - The insertion sequence IS6110/IS986 is used extensively for detecting and typing
      Mycobacterium tuberculosis. In order to appreciate the evolutionary and
      epidemiological significance of differences in the fingerprint pattern, it is
      necessary to understand the factors influencing transposition frequency. Although
      most strains have many copies of this element, some have only one or two copies;
      it has been suggested that this apparent transpositional defect arises from the
      minor differences in the sequence of the element from different strains. In
      contrast, we have found that the sequence is identical in high and low copy
      number strains, indicating that external factors, such as the presence of
      adjacent promoters, must be responsible for differences in copy number.

PMID- 10209677
TI  - Production of avirulent Mycobacterium bovis strains by illegitimate recombination
      with deoxyribonucleic acid fragments containing an interrupted ahpC gene.
AB  - SETTING: Molecular genetic techniques have been used to elucidate virulence
      determinants and to produce vaccines for many bacterial pathogens but reliable
      techniques for slow-growing mycobacteria have not been available. OBJECTIVE:
      Oxidative defence genes including ahpC are involved in isoniazid resistance of
      strains of the Mycobacterium tuberculosis complex. The aim of this study was to
      inactivate ahpC by allelic exchange and to screen the expected background of
      illegitimate recombinants for their inability to grow in minimal medium
      (auxotrophy). DESIGN: M. bovis ATCC35723 was electroporated with linear fragments
      of deoxyribonucleic acid (DNA) containing an ahpC gene interrupted by a kanamycin
      resistance gene. Kanamycin-resistant colonies were screened for allelic exchange
      and auxotrophy. RESULTS: Southern blotting of DNA from kanamycin-resistant
      colonies revealed that no allelic exchange had occurred. Four of these
      recombinants were auxotrophs and subsequently were found to be avirulent in
      guinea pigs. The fragment insertion sites in the chromosome of each auxotroph
      were determined by DNA sequencing. In three cases, large chromosomal deletions
      had occurred. CONCLUSION: The M. bovis ahpC gene was not inactivated by this
      linear fragment approach but illegitimate insertion of such a fragment can be
      successfully used to produce avirulent auxotrophs which have potential for
      vaccine development.

PMID- 10209678
TI  - Comparison of the roles of reactive oxygen and nitrogen intermediates in the host
      response to Mycobacterium tuberculosis using transgenic mice.
AB  - OBJECTIVE: To study the role of reactive oxygen intermediates (ROI) and reactive
      nitrogen intermediates (RNI) in host response to Mycobacterium tuberculosis.
      DESIGN: M. tuberculosis infection (i.v.) was compared in B6 control and two
      strains of knockout (KO) mice. X-CGD mice with a nonfunctional allele for the
      gp91phox subunit of the phagocyte oxidase cytochrome b are unable to produce ROI
      whereas iNOS KO mice lack a functional inducible nitric oxide synthase (iNOS)
      gene and fail to make RNI. RESULTS: M. tuberculosis growth was markedly enhanced
      in the lungs of X-CGD mice compared to B6 mice, but was controlled in the spleen
      and liver. In iNOS KO mice, M. tuberculosis growth was exacerbated in the spleen,
      but was unremarkable in the lungs compared to B6 mice until later (Day 60) in the
      infection. In vitro, X-CGD alveolar and peritoneal macrophages (M phi) produced
      no ROI, but did produce RNI and inhibited growth of M. tuberculosis when
      activated with interferon gamma. iNOS KO M phi produced ROI, but failed to
      produce RNI and could not cope with M. tuberculosis in vitro when activated. The
      inhibition of M. tuberculosis growth observed in activated B6 and X-CGD M phi)
      was reversed in the presence of aminoguanidine. CONCLUSION: These KO mouse
      strains demonstrate the relative potent effects of ROI and RNI in resistance to
      M. tuberculosis and should prove useful for the study of regulatory and
      compensatory mechanisms of immunity.

PMID- 10209679
TI  - Mycobacterium tuberculosis (MTB)-stimulated production of nitric oxide by human
      alveolar macrophages and relationship of nitric oxide production to growth
      inhibition of MTB.
AB  - SETTING: Although nitric oxide (NO) is a major proximate mediator of microbicidal
      activity in murine macrophages against intracellular pathogens including
      mycobacteria, its production by and effector role in human macrophages is not
      clear. OBJECTIVE: To determine the capacity of Mycobacterium tuberculosis (MTB)
      to stimulate NO in human monocytes (MN) and alveolar macrophages (AM) and to
      assess the relationship between NO production and intracellular growth of MTB.
      DESIGN: NO production (measured as nitrite) by MTB (H37Ra)-infected macrophages
      and intracellular growth of MTB were measured in cells from 17 healthy subjects.
      RESULTS: MTB (5:1, MTB:cells) stimulated little to no NO by MN, but induced NO in
      AM at days 4 and 7 after infection. There was, however, variability in the
      response by AM to MTB: among seven subjects MTB-induced NO was low (4 +/- 2
      microM, mean +/- SE); six subjects were moderate (56 +/- 11); four subjects were
      high (502 +/- 167). NO synthase inhibitors inhibited the production of NO by AM
      but did not significantly affect the intracellular growth of MTB, although a
      trend towards increased intracellular growth was seen on day 4 of culture.
      Intracellular growth of MTB in AM from low NO producers was significantly higher
      than that in AM from moderate NO producers, P < or = 0.05. Inducible NO synthase
      (iNOS) mRNA by RT-PCR was constitutively expressed by both MN and AM, but was
      further stimulated by MTB in AM > MN; MTB-induced iNOS protein was present in
      both MN and AM by Western blot analysis. CONCLUSION: Thus, MTB-infected human AM
      are capable of producing NO and NO production correlates with intracellular
      growth inhibition of MTB in AM suggesting that NO may serve either directly or
      indirectly as a mycobactericidal mediator in human tissue macrophages.

PMID- 10209680
TI  - Mycobacterium tuberculosis aerogenic rechallenge infections in B cell-deficient
      mice.
AB  - OBJECTIVE: Use gene disrupted mice to examine the possible role of secretory
      antibody on resistance to re-exposure to pulmonary tuberculosis. DESIGN: Mice
      deficient in B cells due to targeted gene disruption were infected by aerosol
      exposure with Mycobacterium tuberculosis. A further set were identically exposed
      then given isoniazid to clear the infection and establish a state of memory
      immunity. RESULTS: Control of the aerosol infection and generation of gamma
      interferon proceeded in a similar manner in both naive and memory immune mice,
      regardless of B cell deficiency. CONCLUSIONS: The absence of antibody responses
      did not affect the course of infection, thus confirming the classical literature
      that antibody plays no significant protective role.

PMID- 10209681
TI  - Review article: exploring the link between Helicobacter pylori and gastric
      cancer.
AB  - Cancer of the distal stomach, both of the intestinal and diffuse type, is
      strongly associated with Helicobacter pylori colonization. This bacterium causes
      chronic active inflammation of the gastric mucosa in the majority of colonized
      subjects. In a considerable number of them, this will eventually lead to a loss
      of gastric glands, and thus the establishment of atrophic gastritis, which is
      associated with the development of intestinal metaplasia and dysplasia.
      Development of atrophy and metaplasia of the gastric mucosa are thus strongly
      associated with H. pylori infection, instead of a direct and inevitable
      consequence of ageing. Approximately 40-50% of infected subjects develop these
      conditions, but they are rare in non-infected subjects. The presence of these
      consecutive disorders leads to a 5-90-fold increased risk for cancer of the
      distal stomach, in particular of the intestinal type. This sequence explains the
      increased risk for gastric cancer in H. pylori-infected subjects, as has been
      shown in various cross-sectional and longitudinal studies. In a combined analysis
      of three longitudinal studies, a significant trend was observed towards an
      increased odds ratio with longer intervals between (retrospective) serological
      diagnosis of H. pylori infection and observation of gastric cancer, this risk
      being more than eight-fold increased if the interval had been at least 15 years.
      This is thought to reflect development of atrophic gastritis and intestinal
      metaplasia with loss of H. pylori colonization in the years prior to development
      of cancer. Atrophic gastritis and gastric cancer thus appear closely associated
      with the presence of H. pylori, yet not all infected subjects will eventually
      develop atrophy and only a small minority develop gastric cancer. Factors that
      influence the risks for atrophy and cancer in the presence of infection may be
      related to the time that infection occurred and to characteristics of the
      bacterial strain and the host. Evidence for the role of these factors is now
      increasing. Recognition of the causal role of H. pylori in the induction of
      gastric cancer theoretically presents tools for cancer prevention. The efficacy
      of screening and bacterial eradication for prevention of distal gastric cancer is
      being studied in a number of large-scale intervention studies in different
      populations. It is hoped that these studies will also provide answers to the
      potential preventive role of H. pylori colonization in the development of gastro
      oesophageal reflux disease and associated conditions, in particular development
      of cancer of the proximal stomach. Infection with H. pylori plays an important
      role in the aetiology of atrophic gastritis and gastric cancer. Studies suggest
      an eight-fold increased risk for both conditions in the presence of infection.
      Factors that influence the risk for both conditions in the presence of infection
      are the age at which infection occurred and the presence of cagA as a marker for
      more pathogenetic H. pylori strains. The efficacy and side-effects of
      intervention for the prevention of distal gastric cancer has yet to be
      established.

PMID- 10209682
TI  - Review article: the role of inflammation in the pathogenesis of gastric cancer.
AB  - Helicobacter pylori induces infiltration of the gastric mucosa by
      polymorphonuclear cells and macrophages, as well as T and B lymphocytes.
      Paradoxically, this robust immune/inflammatory response cannot clear the
      infection, and thus leaves the host prone to complications resulting from chronic
      inflammation. One adverse consequence of this inflammatory response may be
      gastric cancer, as inflammation has been implicated in the development of
      intestinal metaplasia and mutations in oncogenes that precede the development of
      gastric adenocarcinoma. The gastric inflammatory response is affected somewhat,
      by the strain of H. pylori that infects the host. Thus, the more severe clinical
      manifestation associated with some strains may be attributed to the higher grade
      of inflammation that they induce. Both H. pylori and cytokines induced during
      infection can stimulate the recruitment and activation of inflammatory cells
      including neutrophils and macrophages. When activated, these cells produce
      inflammatory mediators that include reactive oxygen species (ROS). These
      mediators impart an oxidative stress on the cells in the immediate vicinity, in
      this case, the gastric epithelium. Normally, oxidative stress is neutralized by
      natural antioxidants such as vitamin C, however, levels of this antioxidant in
      the gastric juice are decreased during infection. The increased levels of
      oxidants and decreased antioxidants create a stress that can change many
      processes in the gastric epithelium. For example, an accumulation of
      intracellular ROS regulates the expression of many genes and can induce DNA
      damage. Point mutations in the DNA that disrupt the expression and function of
      genes that inhibit cell growth (i.e. p53) are believed to contribute to the
      pathogenesis of gastric cancer. Several studies suggest that epithelial cell
      turnover is affected by the inflammatory response to H. pylori. This notion is
      supported by studies describing an increase in both epithelial cell
      proliferation, as well as cell death by apoptosis, in response to infection.
      Apoptosis is a regulated process of cell death that is triggered by H. pylori as
      well as various inflammatory mediators, including tumour necrosis factor and
      interferon-gamma. Activated T-cells also kill gastric epithelial cells directly.
      Moreover, the host response increases the expression of receptors for H. pylori
      and thus increases bacterial binding and the induction of apoptosis by the
      bacteria. There are several other immune/inflammatory responses that contribute
      to epithelial cell damage mucosa and the pathogenesis of gastric cancer. For
      example, gastric B cells produce autoreactive antibodies that bind to gastric
      epithelial cells. As a consequence of this antigen-antibody complex formation,
      complement becomes activated suggesting that some of the inflammation and
      epithelial cell damage is attributable to immune-complex formation. Epithelial
      cell death can then stimulate the proliferative response of epithelial cell
      precursors. In summary, the proposed model may explain how the gastric
      inflammatory response contributes to the pathogenesis of cancer. This model
      raises the possibility that it could be preferable to identify the patients at
      highest risk of developing gastric cancer and then apply an intervention that
      eliminates the infection and inflammatory response. Alternatively, clinical
      interventions should at least attenuate the oxidative stress that is directly
      attributed to inflammation. These mechanisms have to be examined in the
      paediatric population.

PMID- 10209683
TI  - Panel discussion: breaking the link--clinical options to minimize risk.

PMID- 10209684
TI  - Is the level of pollutants a risk factor for exercise-induced asthma prevalence?
AB  - Increased prevalence of asthma is commonly though to be associated with increased
      air pollution and with lifestyle changes. This study evaluates a possible
      relationship of levels of exposure to outdoor pollutants and exercise-induced
      asthma prevalence. Two groups of students (age 14-17) in distant urban areas were
      randomly selected (n = 649): Group I (n = 430), Vancouver, B.C., Canada; Group II
      (n = 219), Prague, Czech Republic. The free running asthma screening test was
      performed at both locations; self-report questionnaires were distributed to all
      participants. Peak expiratory flow rates were used to evaluate baseline and
      postexercise spirometry. A 15% decrease was considered a positive response to
      exercise challenge. The information on ambient air quality (SO2, NO2, O3, PM10)
      was obtained from appropriate institutions. Of 649 subjects tested [Group I: n =
      430, F = 251 (58.4%,) M = 179 (41.6%) and Group II: n = 219, F = 112 (51.6%), M =
      107 (48.4%)], 81 of the participants (13.2%) responded positively to the exercise
      challenge [Group I: n = 55 (12.8%) and Group II: n = 26 (11.8%)]. Of the
      population tested, 150 (23.6%) participants self-reported a history of allergic
      disease [Group I: 94 (21.9%) and Group II: 56 (25.6%)]. The levels of air
      pollutants obtained for Group II significantly exceeded those obtained for Group
      I. This study reports a prevalence of 12.3% of exercised-induced asthma among
      high school students, when free running asthma screening test and peak expiratory
      flow rate are used. Significantly different levels of common pollutants do not
      correlate with asthma prevalence. Although it is recognized that air pollution is
      a well-known asthma trigger, it cannot be a simple explanation for the continued
      problem of rising asthma prevalence.

PMID- 10209685
TI  - Prevalence of food allergy in 137 latex-allergic patients.
AB  - There have been reports of increased prevalence of certain food allergies in
      patients with Type I latex allergy (LA). A detailed food allergy history was
      obtained from 137 patients with LA. Latex allergy was defined by positive history
      of IgE mediated reactions to contact with latex and positive skin prick test to
      latex and/or positive in vitro test (AlaSTAT and/or Pharmacia CAP). Food allergy
      was diagnosed by a convincing history of possible IgE mediated symptoms occurring
      within 60 minutes of ingestion. We identified 49 potential allergic reactions to
      foods in 29 (21.1%) patients. Foods responsible for these reactions include
      banana 9 (18.3%), avocado 8 (16.3%), shellfish 6 (12.2%), fish 4 (8.1%), kiwi 6
      (12.2%), tomato 3 (6.1%), watermelon, peach, carrot 2 (4.1%) each, and apple,
      chestnut, cherry, coconut, apricot, strawberry, loquat, one (2.0%) each.
      Reactions to foods included local mouth irritation, angioedema, urticaria,
      asthma, nausea, vomiting, diarrhea, rhinitis, or anaphylaxis. Our study confirms
      the earlier reports of increased prevalence of food allergies in patients with
      LA. We also report increased prevalence of shellfish and fish allergy not
      previously reported. The nature of cross reacting epitopes or independent
      sensitization between latex and these foods is not clear.

PMID- 10209686
TI  - Serological investigation of latex allergy in Argentina.
AB  - Atopy to latex has been reported in different high-risk groups of subjects in
      whom it is mainly caused by proteins from natural latex that are responsible for
      eliciting a variety of clinical symptoms, some of them systemic. Thus,
      identification of subjects sensitized to latex proteins is of great health
      importance, because it would become possible to advise them to avoid contact with
      latex-containing products. Protein extracts from ammoniated latex were prepared
      by incubation with PBS buffer either with or without detergents, followed by
      ultracentrifugation. Three immunoenzymic methods were developed (EAST, ELISA, and
      immunoblotting) to detect the presence of specific IgE antibodies against latex
      proteins in sera of patients from different groups at risk. The protein content
      of the latex extracts ranged from 5.3 to 8.8 mg/mL. The prevalence of specific
      IgE against latex proteins was 9/28 (32.1%) in children with multiple surgeries,
      17/98 (17.3%) in health care workers, and 23/123 (18.6%) in outpatients assisted
      at the Allergy Department. None of the sera belonging to the healthy control
      group showed the presence of specific IgE. Therefore, this protein extract from
      latex could be used to detect specific IgE antibodies in serum by immunoenzymic
      methods. Serologic results for latex-specific IgE found are in accordance with
      those reported in the literature of other countries.

PMID- 10209687
TI  - Silk-induced asthma.
AB  - The existence of professional allergens in the home environment is important
      because their avoidance usually resolves the problem completely. We report on a
      case of an asthmatic woman who, for five years, was helping her husband create
      large artistic screens with the cocoons of the silkworms. Extensive laboratory
      evaluation revealed that she was allergic to silk and her symptoms resolved in
      three months following discontinuation of her exposure to silk allergens.

PMID- 10209688
TI  - Determination of cut-off positivity values in nasal challenge testing of patients
      with allergic rhinitis.
AB  - Nasal challenge testing with allergen extracts is currently used to diagnose
      nasal allergy and, to a greater extent, in studies of pathophysiology of allergic
      rhinitis. The resulting nasal obstruction, measured as nasal airway resistance
      (NAR), is determined by rhinomanometry (RMM). The aim of this study was to define
      a cut-off NAR value for a positive response in a nasal allergen challenge test.
      Forty-two, grass-allergic adult patients and 40 nonallergic adults were
      challenged out of the grass pollen season under standard conditions with timothy
      grass extract administered intranasally in doses increasing from 10 to 1500
      IU/mL. Inspiratory NAR was determined by computerized anterior active RMM. The
      cut-off value for a positive test was determined from receiver operating
      characteristic curves plotted from these data with the LABROC1 computer program.
      In addition, the subjects' nasal cycle was recorded during the four hours
      preceding the allergen challenge. The patients' mean NAR value at baseline (0.33
      Pa/cc/sec) and when challenged with normal saline solution did not differ from
      those of the control subjects. The patients, but not the control subjects,
      experienced typical nasal allergic symptoms when challenged with the grass
      extract. The control subjects had no symptoms and their NAR did not change
      significantly when they were challenged with the same extract. All 42 allergic
      patients had measurable increases in NAR at the 800 IU/mL allergen dose; 19/42
      patients had complete obstruction (i.e., NAR unmeasurable) when challenged with
      the 1500 IU/mL dose. The maximum diagnostic value (= sensitivity + specificity at
      the discriminator position on the receiver operating characteristic curves) was
      1.96 with the 800 IU/mL dose. At that dose, the NAR cut-off value was 0.91
      Pa/cc/sec, which was 2.7 times greater than their mean value at baseline. NAR
      varied less than 1-fold between the maximum and minimum points of the normal
      nasal cycle in both groups of subjects. An increase of NAR of nearly three-fold
      during nasal allergen challenge compared to the baseline value determined by
      computerized anterior active RMM discriminates best patients with allergic
      rhinitis from nonallergic adults.

PMID- 10209689
TI  - Platelet-activating factor inhibits ciliary beat frequency of human bronchial
      epithelial cells.
AB  - The aim of our study was to investigate the effect of platelet-activating factor
      on human bronchial ciliary beat frequency (CBF) ex vivo. Brush biopsies were
      obtained from eight children (mean age 6.6 years) who underwent bronchoscopy for
      clinical reasons (i.e., foreign body aspiration, chronic cough, stridor).
      Immediate measurement of CBF by phase-contrast microscopy and photoelectric
      technique was performed before further treatment, and then on three subsamples:
      after adding platelet-activating factor (PAF) (10(-5) M); after adding the
      inhibitor WEB 2086 (10(-4) M); and after adding both PAF and WEB 2086. Addition
      of 10(-5) M PAF reduced mean CBF by 2.1 Hz to 9.2 Hz (p < 0.05). The inhibitory
      effect of PAF was completely reversed by the addition of the PAF-inhibitor WEB
      2086, whereas WEB 2086 alone did not significantly influence CBF. Optimum PAF
      concentration had been determined in previous dose-response experiments. Our data
      indicates that PAF involved in airway inflammation contributes to a decrease in
      mucociliary clearance in humans.

PMID- 10209690
TI  - Serum levels of soluble CD23 in patients with asthma or rhinitis monosensitive to
      Parietaria. Its relation to total serum IgE levels and eosinophil cationic
      protein during and out of the pollen season.
AB  - The diagnostic value for allergies of the low affinity IgE receptor and its
      soluble circulating fragment (sCD23) remains unclear. In particular, little is
      know about seasonal influences on serum sCD23 levels in subjects with pollen
      allergy. In the present study, to gain insight into pathophysiological role of
      sCD23, we have analyzed, in blood from patients allergic to Parietaria sCD23,
      IgE, and eosinophil cationic protein (ECP) serum levels. IgE were assessed as
      atopy markers and ECP as an inflammation marker. Patients were studied during and
      out of pollen season, and results were compared to those obtained in nonallergic
      subjects. The study population included 42 nonsmoking outpatients, living in
      Palermo (Sicily, Italy) or in other west Sicilian towns, with a clinical
      diagnosis of seasonal asthma or rhinitis and monopositive skin test to Parietaria
      pollen. The group of asthmatic subjects consisted of 25 patients who had one or
      more of the usual asthma symptoms (wheezing, dyspnea, and cough) only during the
      pollen season. The group of rhinitis patients consisted of 17 patients, who,
      during pollen season, had the nasal symptoms (nasal blockage, sneezing, nasal
      itching, and rhinorrhoea) but no signs of asthma. As a control group, we studied
      10 nonatopic subjects from laboratory staff. They had no history of seasonal or
      perennial rhinitis, asthma, or urticaria and had negative skin tests to a panel
      of allergens. Soluble CD23, IgE, and ECP were assessed in blood during and out of
      pollen season. Total serum IgE levels were clearly higher in atopic patients, as
      classically established. Concerning sCD23 serum levels, a similar pattern of
      results was obtained. Accordingly, significant correlations were shown between
      the levels of sCD23 and IgE in all groups of patients. A completely different
      pattern was observed by analyzing serum ECP levels because ECP levels were
      significantly increased only in asthmatic patients during pollen season.
      Accordingly, no significant correlations were observed between the levels of
      sCD23 and those of ECP. Identifying immune factors associated with the
      development of atopy can enhance our understanding of the in vivo mechanisms
      involved and may have utility in paradigms designed to prevent diseases. As
      demonstrated by the close correlation with total serum IgE values and the lack of
      correlation with serum ECP values, serum levels of sCD23 appear to be an
      additional marker for the diagnosis of atopy but not for the follow-up of
      allergic diseases.

PMID- 10209691
TI  - Headache and complement C'1-esterase inhibitor deficiency in Vietnamese
      immigrants living in southern California.
AB  - The objective was to measure complement C'1-esterase inhibitor (C1INH) in a group
      of Vietnamese outpatients with headache. All 51 patients (7 males and 44
      females), with either migraine or chronic tension-type headache, were evaluated
      during 1994 and 1995. Their ages ranged from 15 to 69 years old (mean age, 37.5
      years). They were found to have low levels of C1INH (mean, 11 +/- 2 mg/dL versus
      control subjects, 15 +/- 2 mg/dL with p < 0.0001). Twenty patients (5 males and
      15 females) were treated with a low dose of danazol, 200 mg daily for 1-2 months.
      The improvement of the headache coincided with the return to normal levels of
      C1INH in all of our patients (pretreatment, 11 +/- 2 mg/dL versus post-treatment,
      16 +/- 2 mg/dL with p < 0.001). The levels of C1q and C4d/C4 ratios did not
      change as a result of treatment with danazol. Our patients may represent a form
      of androgen-responsive headache, which is associated with low levels of C1INH,
      normal levels of C1q and normal C4d/C4. It differentiated them from angioedema
      (hereditary or acquired form); they had no known precipitating factors or a
      family history of angioedema.

PMID- 10209692
TI  - Anaphylaxis and poetry: Carl A. Dragstedt, M.D., Ph.D. (1895-1983)

PMID- 10209693
TI  - Cognition and the perception of physical symptoms in the community-dwelling
      elderly.
AB  - Elderly people frequently complain of somatic (physical) symptoms that prompt
      them to seek medical intervention. The aim of this study was to evaluate the
      effect of cognitive impairment on somatic symptom complaints by the elderly.
      Symptoms (spontaneously reported and reported after explicit inquiry) pertaining
      to 15 organ systems were assessed in a random sample of 462 community-dwelling
      individuals over the age of 75 years. The symptoms increased with decreasing
      cognitive performance with no, very mild, and mild cognitive impairments as
      indicated on the Mini-Mental State Examination. The trend of increasing reports
      of symptom with decreasing cognitive performance was significant (p = .0001); the
      association remained significant after controlling for potential confounders in
      multivariate analysis (p < .05). The authors, who found that mild cognitive
      impairment was associated with perception of poorer body functioning, suggest
      that the clinical interpretation of somatic symptoms in the elderly should take
      cognitive impairment into account.

PMID- 10209694
TI  - Comparison of clinic, home self-measured, and work self-measured blood pressures.
AB  - Self-measured and clinic blood pressure (BP) estimates of patients' true levels
      of BP were compared as part of a controlled study of stress management training
      for essential hypertension. Forty-three patients underwent 6 to 9 clinic
      measurements and made 48 self-measured readings of BP at home and at work before
      and after treatment. Analyses showed that (a) self-measured BP values at work and
      at home were significantly correlated with each other but did not correlate with
      clinic blood pressure measurements at pretreatment, and (b) test-retest
      correlations over 2 months and intraclass correlations of self-measured BP
      measures were significantly higher than those of clinic BP measurements. Findings
      indicated that self-measurement improved the estimations of patients' true levels
      of BP and improved the sensitivity and feasibility of studies assessing the
      efficacy of antihypertensive treatments.

PMID- 10209695
TI  - Inhibition of emotional expression in breast cancer patients.
AB  - To obtain a better understanding of the inhibited emotional expression often
      reported in breast cancer patients, the authors compared 48 breast cancer
      patients and 49 healthy women with respect to disturbed emotional processes
      (alexithymia), emotional disclosure, emotional expression, assertiveness,
      repression, and distress. The patient group showed significantly more ambivalence
      over emotional expression, more restraint, and more anxiety than the healthy
      controls. No differences were found between the 2 groups in alexithymia,
      expressing emotions in general, or willingness to talk with others about
      emotions. The image of the breast cancer patient that emerged in the study was
      that of a person who has conflicting feelings with regard to expressing emotions,
      is reserved and anxious, is self-effacing, and represses aggression and
      impulsiveness. These findings suggest that cancer patients' inhibited behavior is
      a reaction to the disease rather than a reflection of a personality
      characteristic predisposing an individual to (breast) cancer.

PMID- 10209696
TI  - Predictors of sun protective behaviors among school students.
AB  - A random sample of students (N = 3,655) in Grades 7, 9, and 11 from 55 schools in
      Queensland (Australia) were surveyed about their sun protection knowledge,
      attitudes, and behaviors. An aggregate sun protection behavior index (SPBI) was
      developed from self-reported behaviors on a school day and a weekend day.
      Repeated measures regression analyses revealed that negative views of sun
      protection measures were associated with low scores on the SPBI, an association
      that was strongest among older students and in larger schools. Low perceived
      parental sun protective behaviors were associated with low SPBI ratings, and this
      association was greatest in small schools and on Saturdays. Older students had
      lower SPBI ratings, but their scores increased on Saturdays. Gender did not
      appear to be independently related to the SPBI after adjustment for the other
      variables. These findings reinforce the need for adolescent sun protection
      programs to address the complex interactions among psychological, social, and
      environmental factors that influence different subgroups of the student
      population.

PMID- 10209697
TI  - Differential influences of coping humor and humor bias on mood.
AB  - The authors investigated relationships among sense of humor measured by a
      questionnaire, attentional bias toward humor measured by performance on a word
      search task, and experimentally induced mood change through the use of sad and
      humorous cartoons. Mood was significantly altered in a negative direction after
      the sad cartoon. Coping humor, part of the sense of humor questionnaire, was
      associated with less negative mood ratings after the sad cartoon. In terms of
      main effects, only a modest change in mood was found after the humorous cartoon.
      Humor bias was associated with more positive mood ratings after the humorous
      cartoon. The authors suggest that coping humor serves a protective psychological
      function, helping screen the person from negative stimuli and, thus, from
      negative reactions. Attentional bias toward humor serves a different protective
      psychological function by helping the person focus on mood-enhancing stimuli in
      the environment.

PMID- 10209698
TI  - Disease progression in HIV-positive women with moderate to severe
      immunosuppression: the role of depression. Dana Consortium on Therapy for HIV
      Dementia and Related Cognitive Disorders.
AB  - Thirty-seven HIV-positive women were recruited in a 2-year prospective
      investigation into the role of depression in HIV disease progression. All
      participants had CD4+ cell counts of 200 or less at baseline and at least 3 CD4+
      cell counts during follow-up. Participants were evaluated semiannually for CD4+
      lymphocyte counts, B2Microglobulin (B2M), hemoglobin data, and new AIDS-defining
      illnesses. The Center for Epidemiologic Studies Depression Scale was used to
      assess for depressed mood. Over time, average rates of change in CD4+ counts did
      not differ significantly between depressed and nondepressed women, even after
      adjustment for age, antiretroviral use, and baseline CD4 count, and depressed
      women did not differ from nondepressed women in numbers of new AIDS-defining
      illnesses. The authors concluded that depression may not be a significant
      determinant of disease progression in women with advanced disease and called for
      further investigations with larger samples and women at earlier stages of the
      infection.

PMID- 10209699
TI  - Mizolastine: antihistaminic activity from preclinical data to clinical
      evaluation.
AB  - Mizolastine, a new H1-receptor antagonist, is highly selective for histamine H1
      receptors and has no anticholinergic, antiadrenergic, or antiserotonin activity.
      It is rapidly absorbed after oral ingestion, with peak plasma concentrations
      occurring at 1.5 h. The distribution and terminal elimination half-life values
      are 2 and 13 h, respectively, in healthy young adult volunteers. Half-life values
      are longer in the elderly and in subjects with chronic renal insufficiency;
      however, the differences are not large enough to be clinically relevant or to
      necessitate a dose adjustment in these populations. Mizolastine produces prompt,
      sustained, peripheral blockade of histamine H1 receptors in the skin. Suppression
      of the histamine-induced wheal and flare begins 40-60 min after ingestion of a 10
      mg dose, peaks at 3-4 h, lasts for at least 24 h, and does not decrease during
      regular once-daily dosing. The amount of wheal suppression is comparable to that
      produced by other leading new H1-receptor antagonists. These pharmacokinetic and
      pharmacodynamic studies of mizolastine provide its clinical pharmacology
      'signature'. They also provide the scientific rationale for recommending a once
      daily 10-mg dose and suggest that the efficacy and effectiveness of mizolastine
      will be widely confirmed in allergic disorders, especially rhinitis and
      urticaria.

PMID- 10209700
TI  - What can we learn from murine models of asthma?
AB  - Even though a complex disease such as asthma does not have a comprehensive animal
      model, some characteristics can be duplicated in mice and guinea-pigs. The murine
      model offers advantages with respect to strain control and availability of
      molecular biology tools. We introduced the use of the BP2 'Biozzi' mice, which
      have high IgE titres and expresses bronchopulmonary hyperresponsiveness (BHR)
      after a single antigenic provocation. BHR is accompanied by airway sequestration
      of lymphocytes and eosinophils, and by a newly described IgE-bearing granulocyte,
      identified to basophils. The murine model permits studies for cellular and
      molecular biology and to investigate the mode of action of drugs.

PMID- 10209701
TI  - The current cardiac safety situation with antihistamines.
AB  - Antihistamines (H1-receptor antagonists) are amongst the most frequently
      prescribed drugs worldwide for the treatment of allergic conditions. The clinical
      interest of classical 'first generation' antihistamines is currently rather
      limited by their anticholinergic and sedative properties. The second generation
      of antihistamines, so-called non-sedating antihistamines, are free of these side
      effects. However, since the 1990s, there have been reports that certain non
      sedating antihistamines, mainly terfenadine and astemizole, might be associated
      with the risk of rare but severe dysrhythmias. These drugs prolong the monophasic
      action potential and surface electrocardiographic QT interval and may lead to the
      development of early after-depolarization and possibly torsades de pointes
      through an inhibition of potassium channel repolarization. Concomitant
      administration with drugs that inhibit the hepatic cytochrome P-450 (imidazole
      antifungals, macrolide antibiotics) or those that prolong the QT interval by the
      same or other mechanism (e.g. antiarrhythmics, antipsychotics, tricyclic
      antidepressants) increases their effect on the cardiac repolarization. The
      cardiac safety profile of newer non-sedating antihistamines requires
      confirmation. Drugs with low or no potential to block the K + rectification
      channel (e.g. IKr channels) are likely to possess cardiac safety advantages.
      Other drug-related factors such as the physico-chemical properties of the
      antihistamines and its metabolic profile may also contribute to the cardiac
      response. Mizolastine is a new non-sedating antihistamine with antiallergic
      properties. It has a good bioavailability and a metabolism via the cytochrome P
      450 oxidation accounting for only 35% of its hepatic clearance. In addition,
      mizolastine displays low lipophilicity and consequently low cardiac tissue
      fixation. In clinical studies, mizolastine has not shown any dose-related
      increase in QT intervals. Its clinical use has not been associated with
      ventricular dysrhythmias. Thus, although the post-marketing experience with
      mizolastine is still limited, mizolastine offers a safe alternative for the
      therapeutic management of allergic rhinitis and urticaria. However, more data are
      still needed on the cardiac safety of this and other non-sedating antihistamines.

PMID- 10209702
TI  - Rapid symptom relief in rhinitis.
AB  - In some patients, symptoms of allergic rhinitis can be severe and therefore rapid
      relief is required. There are many treatment options for allergic rhinitis but
      histamine H1 blockers and topical corticosteroids represent the first-line
      treatment. Although the latter drugs are usually very effective on nasal
      symptoms, their onset of action is around 24 h. Thus drugs that are more rapidly
      effective are of interest. Recently 400 French specialists (in Allergy, ENT and
      Pneumology) met together to define the criteria for selecting a drug for the
      treatment of rhinitis. Twelve criteria were proposed and rapid onset of action
      (less than 24 h) was among the foremost designated criteria. In the first trial,
      a comparison of mizolastine (10 mg once daily [od]) with cetirizine (10 mg od)
      and placebo was carried out in the management of seasonal allergic rhino
      conjunctivitis (SAR) with special focus on onset of action. A total of 375
      patients were included in this European multicentric, randomized, parallel group
      and placebo-controlled study. By comparison to placebo, both cetirizine and
      mizolastine reduced significantly nasal and ocular symptoms during the 28-day
      follow-up trial. The percentage of responders ranged from 40% in the placebo
      group to 55% in the mizolastine group and 53% in the cetirizine group. Both
      active drugs were effective from the first intake with a rapid onset within 2 h.
      However, mizolastine was more rapidly and more profoundly effective than
      cetirizine during the first 12 h. A second trial included 257 patients suffering
      from perennial allergic rhino-conjunctivitis (PAR) in a 4-week double-blind
      placebo-controlled multicentric study. During the study, patients recorded, using
      a diary card, ocular and nasal symptoms, including nasal blockage. The mean
      values of nasal score between day 1, 14 and 28 in the mizolastine group were
      statistically significantly lower than those in the placebo group. The mean
      values of ocular score showed a statistical difference in recordings between day
      1 and day 14 in favour of the mizolastine group. Mizolastine was an effective
      drug both in SAR and PAR with a rapid onset of action. Mizolastine relieved
      symptoms more effectively than cetirizine (SAR) and placebo (SAR and PAR) at the
      beginning of treatment.

PMID- 10209703
TI  - Antihistamines in urticaria.
AB  - Urticaria is one of the most common and, in its chronic course, excruciating
      dermato-allergic diseases. Apart from the dermatological diagnosis, the
      identification and evaluation of causal triggering factors is of utmost
      importance. Here a 'three-step guideline' (according to Ring and Przybilla) has
      gained acceptance, ranging a general basic examination via an intensive
      investigation until oral provocation tests for food allergy and oral provocation
      tests for idiosyncrasy (OPTI) against food additives. Apart from true IgE
      mediated allergies, pseudo-allergic reactions against food additives as well as
      food contents represent a major problem in chronic urticaria. Recently gastric
      mucosal colonization with Helicobacter pylori as the trigger of chronic urticaria
      has received attention. New pathophysiological concepts describe autoantibodies
      that are directed either against IgE or against the high-affinity IgE-receptor on
      the surface of mast cells and basophil leucocytes. In the intradermal test with
      autologous serum positive wheal and flare reactions can be observed (Greaves'
      test). In many patients with chronic urticaria considerable psychosomatic
      involvement is also observed. Histamine is one of the major mediators of most
      forms of urticaria although in some cases, especially physical urticaria, other
      mediators seem to play a role. Therefore antihistamines, and mainly H1
      antihistamines, are the mainstay of antiurticaria therapy. Some studies have
      shown a benefit of combined H1- and H2-antagonist treatment in special forms of
      urticaria namely urticaria factitia. Similarly pretreatment with combined H1 and
      H2 antagonists has been proven to reduce effectively the frequency of pseudo
      allergic reaction to some histamine-releasing drugs used in radiology or surgery.
      More than 50 years after the first introduction of an antihistamine into allergy
      therapy, antihistamines still represent modern and exciting agents contributing
      to the continuous improvement of antiallergic therapy. Antihistamine therapy can
      be performed with either the classical or second generation antihistamines.
      Classical antihistamines are connected with considerable side-effects especially
      sedation and anticholinergic effects. New non-sedating antihistamines have been
      developed that do not cross the blood-brain barrier. The efficacy of mizolastine,
      a new non-sedating H1 antagonist, has been evaluated in several placebo
      controlled and comparative clinical trials. Overall, mizolastine 10 mg/day was
      found to be significantly more effective than placebo and as effective as other
      second generation antihistamine drugs in the management of patients with chronic
      urticaria, with a rapid and sustained action.

PMID- 10209704
TI  - [Manufacturers, interventional technicians: unequal combat in materials
      monitoring?].

PMID- 10209705
TI  - [Quality control in bone densitometry].
AB  - Bone densitometry is a biological measurement which must comply to the usual
      rules of quality control. Calibration phantoms are available and must be
      regularly measured. Results may be interpreted by visual inspection or by
      estimating drift percentage. Different calculation methods have been proposed. A
      rigorous procedure is required when replacing densitometry devices. Simple and
      regular controls can assure the reliability of the technique.

PMID- 10209706
TI  - [Brain imaging in AIDS].
AB  - Encephalic diseases remain an important problem in AIDS patients despite
      improvement in the rate of disease spread. We provide data on the current
      situation and describe the clinical, pathological and imaging features commonly
      observed in encephalic diseases in AIDS patients.

PMID- 10209707
TI  - [Lateral view of the thorax: the profile].
AB  - The lateral view of the chest is a complementary incidence performed less
      frequently nowadays with the great frequency of chest CT. In fact, this lateral
      radiograph has important potential and can even give some exclusive information.
      With the 3-dimensional visualization provided by CT, the lateral radiograph of
      the chest is even easier to understand. Following in the footsteps of our great
      predecessors (Felson, Heitzman, Proto) we propose the left lateral view and offer
      our opinion about indications, techniques and results. The left lateral view can
      be performed with perfect perpendicular orientation or with a slight lateral
      shift that can be chosen with the right shoulder forwards (shifted right anterior
      lateral) or the contrary (shifted left anterior lateral). The left lateral view,
      like the antero-posterior view must be interpreted in a circular-concentric
      fashion.

PMID- 10209708
TI  - [Cystic tumors of the kidney in adults: radio-histopathologic correlations].
AB  - The purpose of this study is to provide an updated pathologic-radiologic
      classification of cystic renal tumors and to assess imaging diagnostic
      capabilities. Eighty seven cases of cystic renal tumors explored with
      multimodality imaging (ultrasonography, CT, MRI, arteriography) and with
      histopathologic correlation are reported. The most common cystic carcinomas were
      multilocular cystic renal cell carcinoma (33%) and the pseudocystic necrotic
      carcinoma (31%), which usually belong to category IV. Less common cystic
      carcinomas were unilocular cystic renal cell carcinoma (6%) and renal cyst wall
      carcinoma (6%). The association of thin septa and large locules are suggestive
      findings for multilocular cystic nephroma, but such criteria are not specific
      enough to recognize benign multilocular cystic nephroma and to exclude
      multilocular cystic renal cell carcinoma. Since carcinomatous degeneration may
      occur within the wall of such tumors, especially in von Hippel Lindau disease,
      surgery is still required. The results of our study corroborate the Bosniak
      classification of cystic renal masses: no tumors belonged to the category I or
      II, all cystic masses which belonged to the category IV were malignant tumors,
      category III included benign and malignant tumors.

PMID- 10209709
TI  - [Radiologic aspects of the complications of duodenal diverticula].
AB  - The duodenum is the second most common site, after the colon, for intestinal
      diverticulae. This condition is most often asymptomatic and is usually an
      accidental finding. Complications, with variable clinical presentations, may
      occur in up to 5% of such individuals. We report a retrospective analysis of 5
      patients who presented with complicated duodenal diverticular disease. The
      complications, either isolated or multiple, consisted of bezoar formation (n =
      2), diverticulitis (n = 2), extrinsic compression of the common bile duct (n =
      3), perforation (n = 1), choledocholithiasis (n = 1), and an abnormality of the
      bilio-pancreatic ductal convergence (n = 1). The radiological aspects, in
      particular, the magnetic resonance imaging (MRI) features are reviewed. These
      are, to our knowledge, the first descriptions of MRI and magnetic resonance
      cholangiopancreatographic (MRCP) findings in complicated duodenal diverticular
      disease. MRI facilitates precise delineation of the complicated duodenal
      diverticulum while MRCP allows assessment of the effects on the biliary and
      pancreatic ducts.

PMID- 10209710
TI  - [Is there criteria to allow the selection of patients exposed to asbestos which
      is relevant to thoracic computed tomography screening?].
AB  - OBJECTIVE: This study was undertaken to determine whether certain criteria could
      be used to select among asbestos-exposed subjects those who could benefit from
      computed tomography screening. MATERIALS AND METHODS: Search for criteria
      enabling the selection of patients who should undergo a CT screening exam after
      occupational exposure to asbestos was conducted in 150 subjects. All subjects
      were explored with selected high-resolution CT scans. Studied parameters were
      age, exposure data, pulmonary function test results. RESULTS: None of the
      exposure data or pulmonary function test results suggested with certainty the
      presence or absence of asbestos-related pleural and parenchymal lung disease. The
      studied parameters could not be used to select patients who could benefit from CT
      screening. CONCLUSION: None of the studied parameters enabled a selection of
      asbestos-exposed subjects who should undergo chest CT screening.

PMID- 10209711
TI  - [Isolated lumbar intradural hydatid cyst].
AB  - Intradural hydatidosis is a very uncommon form of vertebrospinal hydatidosis. We
      report a intradural lumbar localization, presenting the magnetic resonance
      imaging findings. We emphasize MRI for diagnosis and follow-up in search for
      residual or recurrent lesions.

PMID- 10209712
TI  - [Retroperitoneal non-secreting paraganglioma].
AB  - Paraganglioma is a rare tumor arising from indifferentiated cells of the
      primitive neural crest. These tumors are most commonly found in the adrenal gland
      but other localisations are possible. We described a 60-year-old men with a right
      retro-peritoneal mass discovered on ultrasound examination. This tumor had an
      heterogeneous appearance on i.v. contrast injected CT (computed tomography) and
      MR (magnetic resonance) images. Plasma and urinary catecholamines were normal.
      This tumor was surgically removed. Immunohistochemical analyses revealed that the
      tumor cells were strongly positive for neurone specific enolase and chromogranin
      A. Histopathologic examination diagnosed a non secreting paraganglioma in the
      right retroperitoneum. After surgery, the patient remained asymptomatic without
      treatment.

PMID- 10209713
TI  - [Spontaneous regression of a false aneurysm of the ascending aorta following
      surgery for dissection].
AB  - We report the case of a 50-year-old man admitted to hospital for a type A aortic
      dissection. After conventional surgical repair, he was asymptomatic and underwent
      computed tomography imaging at 15 days, 3 and 6 months. The first CT scan showed
      a small perigraft circulating false aneurysm which totally disappeared on the
      last exam. This case emphasizes the potential role of CT scan in the follow-up of
      patient after aortic surgery and the likely favorable outcome of some false
      aneurysm.

PMID- 10209714
TI  - [What is it? Histiocytosis X].

PMID- 10209716
TI  - [Otorhinolaryngologic and maxillofacial imaging].

PMID- 10209715
TI  - [Cervical epidural injection technic under computed tomography guidance in the
      treatment of cervicobrachial neuralgia].
AB  - Epidural injections of corticosteroids in the cervical spine can provide
      effective treatment of cervicobrachial neuralgia. This technique is mainly
      described by anesthesiologists who perform injections without imaging control. We
      demonstrate that this infiltration can be easily performed under CT-guidance by
      radiologists.

PMID- 10209717
TI  - [Radio-anatomy of the larynx].

PMID- 10209718
TI  - [Imaging of the cancerous larynx].

PMID- 10209719
TI  - [Radio-anatomy of the oropharynx].

PMID- 10209720
TI  - [Optimization of imaging technics in the study of tumors of the pharynx, larynx
      and oral cavity].

PMID- 10209721
TI  - [Radio-anatomy of the temporomandibular joint].

PMID- 10209722
TI  - [Static and dynamic MRI of the temporomandibular joint].

PMID- 10209723
TI  - Glaucoma imaging: technology in progress.

PMID- 10209724
TI  - Interocular symmetry in nerve fiber layer thickness of normal eyes as determined
      by polarimetry.
AB  - PURPOSE: The existence of asymmetries between the two eyes in number and
      distribution of nerve fibers may provide an early anatomic indication of
      glaucomatous disruption if a symmetrical pattern of nerve fibers can be shown in
      normal eyes. Normal eyes were tested to determine whether a high degree of
      correspondence of regional nerve fiber layer thickness exists between fellow
      eyes. METHODS: Nerve fiber layer thickness was inferred from retardation shift
      measured by a scanning laser polarimeter (Laser Diagnostic Technologies, Inc.) in
      40 volunteers without glaucoma or ocular disease (80 eyes). Total thickness and
      the pattern of nerve fiber thickness over 208 regions was compared between the
      paired eyes. RESULTS: Inferred nerve fiber layer thickness in companion eyes was
      highly correlated. Variation of the total nerve fiber thickness was much less
      between companion eyes than between eyes of different individuals. In terms of
      regional (i.e., local) interocular correspondence, the measurements in the
      inferior retina were observed to be highly similar in the two eyes, but a
      pronounced shift of the location of the superior peak (maximum thickness) in the
      left eye relative to the right was observed, as were differences between the two
      eyes in the thickness measurements at the nasal and temporal minima. CONCLUSION:
      Significant interocular asymmetries were detected in regions other than the
      interior hemiretina. These interocular asymmetries may reflect previously
      unrecognized anatomic nerve fiber differences or systematic angular bias in the
      instrument for one eye relative to the other. In contrast to the regional
      measures, the measures of total thickness were very similar between companion
      eyes, suggesting that the assessment of interocular asymmetries of total
      thickness determined by polarimetry may offer potential for detecting glaucoma.

PMID- 10209725
TI  - Agreement in assessing glaucomatous discs in a clinical teaching setting with
      stereoscopic disc photographs, planimetry, and laser scanning tomography.
AB  - PURPOSE: Agreement between three observers--two recently trained fellows and
      their supervisor--was measured using estimations of cup/disc ratio from
      stereoscopic optic nerve head photographs and planimetric measurements of
      cup/disc ratio. Agreement between the clinicians' planimetric measurements of
      cup/disc ratio and laser scanning tomographic measurements of cup/disc ratio also
      was assessed. METHODS: From 16 stereoscopic optic nerve head photographs of 16
      subjects, the three observers performed clinical estimations of horizontal and
      vertical cup/disc ratios and planimetric measurements of cup/disc ratios.
      Interobserver agreement was measured using intraclass correlation coefficients
      (ICCs). Agreement between the planimetric cup/disc ratios and laser scanning
      tomographic cup/disc ratios obtained with the Heidelberg Retina Tomograph (HRT;
      Heidelberg Engineering, Heidelberg, Germany) also was measured using ICCs. The
      difference between the planimetric and HRT cup/disc ratios was calculated.
      RESULTS: The agreement between observers for clinical estimations from
      stereoscopic optic nerve head photographs (ICC = 0.74 horizontally and 0.83
      vertically) was substantial. Agreement between the observers' planimetric
      measurements of cup/disc ratio was substantial (ICC = 0.79). Agreement between
      HRT cup/disc ratio and each observer's planimetric cup/disc ratio was moderate
      (ICC = 0.57-0.65), with large confidence intervals. The cup/disc ratio measured
      with HRT was an average of 0.07 to 0.11 larger than the planimetric cup/disc
      ratio. CONCLUSION: Substantial agreement between observers can be achieved when
      estimating cup/disc ratio with stereoscopic optic nerve head photographs and with
      planimetric measurements of cup/disc ratios, provided there is a standard
      protocol and sufficient training period. Good agreement is critical in a teaching
      institution to ensure accurate follow-up care of patients with glaucoma,
      especially if patients are examined by different clinicians. Laser scanning
      tomography is a more repeatable and objective method, which may provide further
      standardization of optic nerve head assessments. Future studies will determine
      the reference plane that optimizes agreement between the HRT findings and each
      clinician's estimations.

PMID- 10209726
TI  - Agreement of measurement of parapapillary atrophy with confocal scanning laser
      ophthalmoscopy and planimetry of photographs.
AB  - PURPOSE: To evaluate whether parapapillary atrophy can be measured interactively
      using confocal scanning laser ophthalmoscopy. METHODS: For 36 patients with open
      angle glaucoma or suspected of having glaucoma, confocal scanning laser
      ophthalmoscopy of the optic nerve head was performed using the Heidelberg Retina
      Tomograph (HRT; Heidelberg Engineering, Heidelberg, Germany). Alpha and beta
      zones of parapapillary atrophy were plotted independently by two examiners on HRT
      images before and after reviewing optic disc photographs. These data were
      compared with planimetric measurements obtained from analyzing the disc
      photographs. RESULTS: Before viewing the disc photographs, assessment using the
      HRT images correlated better with the beta zone than alpha zone planimetric
      measurements. If the HRT images were evaluated while simultaneously viewing disc
      photographs, correlation coefficients increased for both examiners 1 and 2.
      Interobserver and intraobserver reliability were 0.431 and 0.802, respectively,
      for alpha zone, and 0.882 and 0.948, respectively, for beta zone. CONCLUSION:
      Parapapillary atrophy can be estimated with confocal scanning laser
      ophthalmoscopy. Correlation with planimetric measurements is best if conventional
      optic disc photographs are simultaneously viewed. Intraobserver and interobserver
      reliability are higher for beta zone than for alpha zone.

PMID- 10209727
TI  - Regulation of intraocular pressure after water drinking.
AB  - PURPOSE: Acute oral water loading transiently elevates intraocular pressure (IOP)
      via mechanisms that remain unexplained. We tested the possibilities that water
      drinking might elevate IOP by creating a blood-aqueous osmotic gradient, or that
      it might instead alter active ion pumping and the formation of aqueous humor.
      METHODS: In the first series, 16 young, healthy individuals were studied during
      dehydration and for 1 hour after rehydration (14 mL H2O/kg body weight).
      Hematocrit, total plasma osmolality, and plasma colloid osmotic pressure were
      determined simultaneously with measurements of IOP. In a second series (N = 16),
      rehydration occurred after pretreatment with either placebo or a topical carbonic
      anhydrase inhibitor (1 drop 2% dorzolamide in each eye, 12 and 2 hours before
      oral water loading). RESULTS: In both series, mean IOP increased significantly 15
      minutes after water ingestion and remained elevated above baseline for 45
      minutes. In contrast, colloid osmotic pressure and hematocrit were unaltered by
      water drinking, and neither these variables nor total plasma osmolality
      correlated with IOP. In the second series, pretreatment with dorzolamide reduced
      baseline IOP, but failed to alter the magnitude or time course of IOP elevations
      induced by water drinking. CONCLUSION: Because water drinking failed to create a
      blood-ocular osmotic pressure gradient, neither vitreous hydration nor increased
      aqueous ultrafiltration can explain increases in IOP after acute hydration.
      Because the increase in ocular tension apparently also is independent of active
      bicarbonate pumping, factors affecting aqueous drainage must explain the water
      drinking effect.

PMID- 10209728
TI  - Effects of oral brovincamine on visual field damage in patients with normal
      tension glaucoma with low-normal intraocular pressure.
AB  - PURPOSE: To prospectively study the effect of oral brovincamine, a relatively
      selective cerebral vasodilator, on further deterioration of visual field in
      patients with normal-tension glaucoma (NTG) with low-normal intraocular pressure
      (IOP). METHODS: Fifty-two patients with NTG (average age 57.7 years) with an IOP
      that was consistently less than 15 mmHg were randomly assigned to receive oral
      brovincamine (20 mg three times daily) or to an untreated control group. The
      groups were prospectively followed for 2 years with visual field examinations
      every 4 months, using the 30-2 Humphrey perimeter program. Changes in mean
      deviation (MD), corrected pattern standard deviation (CPSD), and total deviation
      (TD) at 74 test points were analyzed using regression analysis with linear mixed
      model. Data from one eye without media opacity of each subject were analyzed.
      RESULTS: There were no differences between groups in age; sex distribution;
      refraction; blood pressure; baseline IOP; MD, CPSD, or TD at each point. Changes
      in MD (standard error [SE]) during the study period were -0.778 (0.178) and 
      0.071 (0.195) dB/year in the control and brovincamine groups, respectively;
      change in the control group was significantly more negative than in the
      brovincamine group. Change in CPSD (SE) was 0.032 (0.015) and 0.004 (0.016)
      dB/year in the control and brovincamine groups, respectively. Change in the
      control group was significantly positive, but the intergroup difference was not
      significant. Change in TD was significantly negative at six test points in the
      control group, whereas no points showed a significant trend in the brovincamine
      group; the intergroup difference was significant. The average IOP was 13.2 mmHg
      and 13.1 mmHg in the control and brovincamine groups, respectively, and there was
      no significant intergroup difference. CONCLUSION: Oral brovincamine may retard
      further visual field deterioration in patients with NTG who have low-normal IOP.

PMID- 10209729
TI  - Fornix-based versus limbal-based conjunctival flaps in initial trabeculectomy
      with postoperative 5-fluorouracil: four-year follow-up findings.
AB  - PURPOSE: To evaluate the safety and efficacy of fornix-based conjunctival flap
      versus limbal-based flap in initial trabeculectomy with postoperative 5
      fluorouracil. METHODS: 29 patients (58 eyes) with bilateral primary open-angle
      glaucoma (POAG) were included in the study. Patients were randomly assigned to
      have a fornix-based conjunctival flap in one eye and a limbal-based flap in the
      other, followed by subconjunctival injection of 5-fluorouracil. RESULTS: Mean
      intraocular pressure (IOP) 2 years after treatment was 12.9 +/- 12.25 mmHg in
      eyes with fornix-based conjunctival flaps and 13.1 +/- 16.81 mmHg in eyes with
      limbal-based conjunctival flaps. At 4 years, mean IOP was 14.7 +/- 9.61 mmHg in
      eyes with fornix-based conjunctival flaps and 15.1 +/- 7.29 mmHg in eyes with
      limbal-based conjunctival flaps. Cumulative success at 4 years (IOP < 21 mmHg)
      was 89.6% in eyes with fornix-based conjunctival flaps versus 86.2% in eyes with
      limbal-based conjunctival flaps with medications. Cystic leaking blebs occurred
      in two cases, both with limbal-based flaps. CONCLUSION: The efficacy of limbal-
      and fornix-based conjunctival flaps in initial trabeculectomy with postoperative
      5-fluorouracil was not significantly different; however, in this study cystic
      leaking blebs were encountered only in eyes with limbal-based conjunctival flaps.

PMID- 10209730
TI  - Ciliary body melanocytoma with anterior segment pigment dispersion and elevated
      intraocular pressure.
AB  - PURPOSE: To discuss a case in which melanocytoma of the ciliary body presented
      with widespread pigment dispersion and elevated intraocular pressure (IOP).
      METHODS: A 64-year old woman presented with increased IOP and persistent anterior
      segment inflammation in her right eye. She had undergone a trabeculectomy for
      uncontrolled IOP before presentation. Slit-lamp examination, gonioscopy, and
      ultrasound biomicroscopy revealed a ciliary body mass with extension into the
      subconjunctiva in addition to widespread pigmentary dispersion in the anterior
      segment. Enucleation of the right eye was performed for histopathologic
      evaluation, as a diagnosis of ciliary body melanoma was made on clinical
      examination. RESULTS: Histopathologic findings were diagnostic of a melanocytoma
      of the ciliary body with necrosis and focal malignant transformation with
      extension of melanocytoma cells and melanophages into the subconjunctival space,
      trabecular meshwork, and anterior chamber angle. CONCLUSION: Melanocytoma of the
      ciliary body is a rare intraocular tumor that may present with pigment dispersion
      and secondary elevated IOP. Careful examination of the anterior segment is
      imperative in such cases.

PMID- 10209732
TI  - Early magnocellular loss in glaucoma demonstrated using the pseudorandomly
      stimulated flash visual evoked potential.
AB  - PURPOSE: Components of the pseudorandomly stimulated flash visual evoked
      potential (VEP) have now been identified that appear to arise predominantly from
      each of the magnocellular (M-cell) and parvocellular (P-cell) systems. In this
      study, the relative damage to magnocellular and parvocellular systems at
      different stages of glaucoma using pseudorandomly stimulated flash VEP was
      investigated. METHODS: Pseudorandomly stimulated flash VEP was recorded in 15
      normal eyes and 28 eyes with different stages of glaucoma using the VERIS-3
      recording system (Electro-Diagnostic Imaging, San Francisco, CA). Two levels of
      luminance contrast of the stimulus (32% and 99%) were tested. The first slice of
      the second-order kernel from only the central (8 degrees) stimulated area was
      extracted for analysis. RESULTS: Data recorded from normal eyes demonstrated
      early saturation of the response/contrast function of the first slice of the
      second-order kernel. The ratio of the VEP amplitude recorded at 32% and 99% of
      the luminance contrast was close to unity. In eyes with early glaucoma, although
      the amplitude of the responses to both low- and high-contrast stimulation
      decreased, the relative reduction of the low-contrast VEP (M-cell) was more
      prominent. However, the amplitude of the high-contrast response (P-cell) declined
      more rapidly later in the disease. CONCLUSION: These results are consistent with
      relatively earlier damage of the magnocellular pathway in glaucoma.

PMID- 10209731
TI  - Chronic open-angle glaucoma and associated ophthalmic findings in monozygotic
      twins and their spouses in Iceland.
AB  - PURPOSE: To determine the concordance of glaucoma and ocular parameters in
      monozygotic twins and their spouses. METHODS: This was a prospective study that
      included 50 twin pairs 55 years of age or older and 47 of their spouses. Zygosity
      was determined by genetic laboratory testing. RESULTS: The concordance of open
      angle glaucoma in monozygotic twin pairs was 98.0%, which significantly exceeded
      that of twin/spouse pairs (70.2%). There was a significant association in mean
      intraocular pressure (IOP), mean axial length, anterior chamber depth, and
      refractive error in the twin pairs. However, there was no association between the
      twins and their spouses for these ocular parameters. Eight twin pairs were found
      to have pseudoexfoliation syndrome (PXFS), five of which were concordant. There
      was no association between glaucoma and mean axial length or glaucoma and
      refractive error in the twin pairs studied. CONCLUSION: The statistically
      significant higher concordance of glaucoma--and the high correlation of mean IOP,
      mean axial length, anterior chamber depth, and refractive error--in twin pairs
      and the lack of association of these factors in twin/spouse pairs strongly
      suggests the importance of genetic factors for these ocular parameters.

PMID- 10209733
TI  - Malignant glaucoma.

PMID- 10209734
TI  - A GLC1A gene Gln368Stop mutation in a patient with normal-tension open-angle
      glaucoma.
AB  - PURPOSE: To present a case involving a patient with normal-tension glaucoma with
      a Gln368Stop mutation of the myocilin/trabecular meshwork inducible
      glucocorticoid response protein (MYOC/TIGR) gene. METHODS: Slit-lamp
      biomicroscopic and gonioscopic examination, morphometry of the optic disc, 24
      hour intraocular pressure (IOP) profile, and perimetry were performed to
      determine the phenotype of the patient. Neurologic examination and a computed
      tomographic (CT) scan of the brain were performed to rule out a neurologic
      disorder. Single-strand confirmation polymorphism (SSCP) analysis and subsequent
      sequence analysis of blood was performed for genotyping of the GLC1A gene.
      RESULTS: A nonsense codon, namely a Gln368Stop mutation in the third exon of the
      GLC1A gene, was found in this patient with normal-tension glaucoma. CONCLUSION:
      In contrast to previous reports, a Gln368Stop mutation of the GLC1A gene need not
      be confined to patients with glaucomatous optic atrophy due to high IOP. The
      pathogenesis of glaucoma associated with GLC1A gene mutations might be more
      complex than expected, and (unknown) suppressor mechanisms have to be considered.

PMID- 10209735
TI  - Mycobacterium tuberculosis phagosome.
AB  - The arrest of Mycobacterium tuberculosis phagosome maturation in infected
      macrophages is a phenomenon of dual significance both for the pathogenesis of
      tuberculosis and as a model system to study interference of microbes with
      membrane trafficking and organelle biogenesis in host cells. Among other factors,
      compartment-specialized regulators of vesicular trafficking and other parts of
      membrane fusion machinery are likely to play a role in these processes. Here we
      summarize the emerging view of mycobacterial phagosome maturation arrest in the
      context of the dynamic processes of intracellular membrane trafficking.

PMID- 10209736
TI  - Termination of DNA replication of bacterial and plasmid chromosomes.
AB  - Sequence-specific replication termini occur in many bacterial and plasmid
      chromosomes and consist of two components: a cis-acting ter site and a trans
      acting replication terminator protein. The interaction of a terminator protein
      with the ter site creates a protein-DNA complex that arrests replication forks in
      a polar fashion by antagonizing the action of the replicative helicase (thereby
      exhibiting a contrahelicase activity). Terminator proteins also arrest RNA
      polymerases in a polar fashion. Passage of an RNA transcript through a terminus
      from the non-blocking direction abrogates replication termination function, a
      mechanism that is likely to be used in conditional termini or replication check
      points.

PMID- 10209737
TI  - Type III machines of pathogenic yersiniae secrete virulence factors into the
      extracellular milieu.
AB  - Gram-negative bacteria use type III machines to inject toxic proteins into the
      cytosol of eukaryotic cells. Pathogenic Yersinia species export 14 Yop proteins
      by the type III pathway and some of these, named effector Yops, are targeted into
      macrophages, thereby preventing phagocytosis and allowing bacterial replication
      within lymphoid tissues. Hitherto, YopB/YopD were thought to insert into the
      plasma membrane of macrophages and to promote the import of effector Yops into
      the eukaryotic cytosol. We show here that the type III machines of yersiniae
      secrete three proteins into the extracellular milieu (YopB, YopD and YopR).
      Although intrabacterial YopD is required for the injection of toxins into
      eukaryotic cells, secreted YopB, YopD and YopR are dispensable for this process.
      Nevertheless, YopB, YopD and YopR are essential for the establishment of Yersinia
      infections in a mouse model system, suggesting that type III secretion machines
      function to deliver virulence factors into the extracellular milieu also.

PMID- 10209738
TI  - Delivery of protein to the cytosol of macrophages using Escherichia coli K-12.
AB  - Listeriolysin O (LLO) is an essential determinant of pathogenicity whose natural
      biological role is to mediate lysis of Listeria monocytogenes containing
      phagosomes. In this study, we report that Escherichia coli expressing cytoplasmic
      recombinant LLO can efficiently deliver co-expressed proteins to the cytosol of
      macrophages. We propose a model in which subsequent or concomitant to
      phagocytosis the E. coli are killed and degraded within phagosomes causing the
      release of LLO and target proteins from the bacteria. LLO acts by forming large
      pores in the phagosomal membrane, thus releasing the target protein into the
      cytosol. Delivery was shown to be rapid, within minutes after phagocytosis. Using
      this method, a large enzymatically active protein was delivered to the cytosol.
      Furthermore, we demonstrated that the E. coli/LLO system is very efficient for
      delivery of ovalbumin (OVA) to the major histocompatibility (MHC) class I pathway
      for antigen processing and presentation, greater than 4 logs compared with E.
      coli expressing OVA alone. Moreover, the time required for processing and
      presentation of an OVA-derived peptide was similar to that previously reported
      when purified OVA was introduced directly into the cytosol by other methods.
      Using this system, potentially large amounts of any protein that can be expressed
      in E. coli can be delivered to the cytosol without protein purification. The
      potential use of this system for the delivery of antigenic protein in vivo and
      the delivery of DNA are discussed.

PMID- 10209739
TI  - IHF protein inhibits cleavage but not assembly of plasmid R388 relaxosomes.
AB  - Relaxosomes are specific nucleoprotein structures involved in DNA-processing
      reactions during bacterial conjugation. In this work, we present evidence
      indicating that plasmid R388 relaxosomes are composed of origin of transfer
      (oriT) DNA plus three proteins TrwC relaxase, TrwA nic-cleavage accessory protein
      and integration host factor (IHF), which acts as a regulatory protein. Protein
      IHF bound to two sites (ihfA and ihfB) in R388 oriT, as shown by gel retardation
      and DNase I footprinting analysis. IHF binding in vitro was found to inhibit nic
      cleavage, but not TrwC binding to supercoiled DNA. However, no differences in the
      frequency of R388 conjugation were found between IHF- and IHF+ donor strains. In
      contrast, examination of plasmid DNA obtained from IHF- strains revealed that
      R388 was obtained mostly in relaxed form from these strains, whereas it was
      mostly supercoiled in IHF+ strains. Thus, IHF could have an inhibitory role in
      the nic-cleavage reaction in vivo. It can be speculated that triggering of
      conjugative DNA processing during R388 conjugation can be mediated by IHF release
      from oriT.

PMID- 10209740
TI  - Characterization and modelling of VanT: a novel, membrane-bound, serine racemase
      from vancomycin-resistant Enterococcus gallinarum BM4174.
AB  - Sequence determination of a region downstream from the vanXYc gene in
      Enterococcus gallinarum BM4174 revealed an open reading frame, designated vanT,
      that encodes a 698-amino-acid polypeptide with an amino-terminal domain
      containing 10 predicted transmembrane segments. The protein contained a highly
      conserved pyridoxal phosphate attachment site in the C-terminal domain, typical
      of alanine racemases. The protein was overexpressed in Escherichia coli, and
      serine racemase activity was detected in the membrane but not in the cytoplasmic
      fraction after centrifugation of sonicated cells, whereas alanine racemase
      activity was located almost exclusively in the cytoplasm. When the protein was
      overexpressed as a polypeptide lacking the predicted transmembrane domain, serine
      racemase activity was detected in the cytoplasm. The serine racemase activity was
      partially (64%) inhibited by D-cycloserine, whereas host alanine racemase
      activity was almost totally inhibited (97%). Serine racemase activity was also
      detected in membrane preparations of constitutively vancomycin-resistant E.
      gallinarum BM4174 but not in BM4175, in which insertional inactivation of the
      vanC-1 D-Ala:D-Ser ligase gene probably had a polar effect on expression of the
      vanXYc and vanT genes. Comparative modelling of the deduced C-terminal domain was
      based on the alignment of VanT with the Air alanine racemase from Bacillus
      stearothermophilus. The model revealed that almost all critical amino acids in
      the active site of Air were conserved in VanT, indicating that the C-terminal
      domain of VanT is likely to adopt a three-dimensional structure similar to that
      of Air and that the protein could exist as a dimer. These results indicate that
      the source of D-serine for peptidoglycan synthesis in vancomycin-resistant
      enterococci expressing the VanC phenotype involves racemization of L- to D-serine
      by a membrane-bound serine racemase.

PMID- 10209741
TI  - The replication checkpoint control in Bacillus subtilis: identification of a
      novel RTP-binding sequence essential for the replication fork arrest after
      induction of the stringent response.
AB  - We have shown previously that induction of the stringent response in Bacillus
      subtilis resulted in the arrest of chromosomal replication between 100 and 200 kb
      either side of oriC at distinct stop sites, designated LSTer and RSTer, left and
      right stringent terminators respectively. This replication checkpoint was also
      shown to involve the RTP protein, normally active at the chromosomal terminus. In
      this study, we show that the replication block is absolutely dependent upon RelA,
      correlated with high levels of ppGpp, but that efficient arrest at STer sites
      also requires RTP. DNA-DNA hybridization data indicated that one or more such
      LSTer sites mapped to gene yxcC (-128 kb from oriC). A 7.75 kb fragment
      containing this gene was cloned into a theta replicating plasmid, and plasmid
      replication arrest, requiring both RelA and RTP, was demonstrated. This effect
      was polar, with plasmid arrest only detected when the fragment was orientated in
      the same direction with respect to replication, as in the chromosome. This LSTer2
      site was further mapped to a 3.65 kb fragment overlapping the next40 probe.
      Remarkably, this fragment contains a 17 bp sequence (B'-1) showing 76% identity
      with an RTP binding site (B sequence) present at the chromosomal terminus. This
      B'-1 sequence, located in the gene yxcC, efficiently binds RTP in vitro, as shown
      by DNA gel retardation studies and DNase I footprinting. Importantly, precise
      deletion of this sequence abolished the replication arrest. We propose that this
      modified B site is an essential constituent of the LSTer2 site. The differences
      between arrest at the normal chromosomal terminus and arrest at LSTer site are
      discussed.

PMID- 10209743
TI  - Insertion of EspD into epithelial target cell membranes by infecting
      enteropathogenic Escherichia coli.
AB  - Diffusely adhering Escherichia coli (DAEC) strains have been implicated in
      epidemiological studies as a cause of diarrhoea in children. However, the
      molecular interactions of these pathogens with target cells have remained largely
      obscure. We found that some DAEC strains contain homologues of the locus of
      enterocyte effacement (LEE) pathogenicity island and secrete EspA, EspB and EspD
      proteins necessary for the formation of the attaching and effacing (A/E) lesions.
      To characterize the function of the EspD protein further, we cloned and sequenced
      the espD genes of two DA-EPEC strains and compared their deduced amino-acid
      sequences with known EspD sequences. A pattern of two conserved transmembrane
      regions and one conserved coiled-coil region is predicted in EspD and also in the
      type III system secreted proteins YopB, PopB, IpaB and SipB of Yersinia,
      Pseudomonas, Shigella and Salmonella respectively. The EspD protein is inserted
      into a trypsin-sensitive location in the HeLa cell membrane at sites of bacterial
      contact, but is not translocated into the cytoplasm. Secretion of EspD increases
      upon contact with host cells. We propose that the membrane-located EspD protein
      is part of the translocation apparatus for Esp proteins into the target host cell
      performing functions similar to YopB in Yersinia.

PMID- 10209742
TI  - Multiple transcription factors of the FNR family in denitrifying Pseudomonas
      stutzeri: characterization of four fnr-like genes, regulatory responses and
      cognate metabolic processes.
AB  - Pseudomonas stutzeri is a facultative anaerobic bacterium with the capability of
      denitrification. In searching for regulators that control the expression of this
      trait in response to oxygen withdrawal, we have found an unprecedented
      multiplicity of four genes encoding transcription factors of the FNR family. The
      fnrA gene encodes a genuine FNR-type regulator, which is expressed constitutively
      and controls the cytochrome cbb3-type terminal oxidase (the cco operon),
      cytochrome c peroxidase (the ccp gene) and the oxygen-independent
      coproporphyrinogen III oxidase (the hemN gene), in addition to its previously
      demonstrated role in arginine catabolism (the arc operon). The fnr homologues
      dnrD, dnrE and dnrS encode regulators of a new subgroup within the FNR family.
      Their main distinctive feature is the lack of cysteine residues for complexing
      the [4Fe-4S] centre of redox-active FNR-type regulators. However, they form a
      phylogenetic lineage separate from the FixK branch of FNR proteins, which also
      lack this cysteine signature. We have studied the expression of the dnr genes
      under aerobic, oxygen-limited and denitrifying conditions. DnrD is a key
      regulator of denitrification by selective activation of the genes for cytochrome
      cd1 nitrite reductase and NO reductase. The dnrD gene is part of the 30 kb region
      carrying denitrification genes of P. stutzeri. Transcription of dnrD was
      activated in O2-limited cells and particularly strongly in denitrifying cells,
      but was not under the control of FnrA. In response to denitrifying growth
      conditions, dnrD was transcribed as part of an operon together with genes
      downstream and upstream of dnrD. dnrS was found about 9 kb upstream of dnrD, next
      to the nrdD gene for anaerobic ribonucleotide reductase. The transcription of
      dnrS required FnrA in O2-limited cells. Mutation of dnrS affected nrdD and the
      expression of ferredoxin I as an element of the oxidative stress response. The
      dnrE gene is part of the nar region encoding functions for respiratory nitrate
      reduction. We found the highest amount of dnrE transcripts in aerobically nitrate
      challenged cells. The gene was transcribed from two promoters, P1 and P2, of
      which promoter P1 was under the control of the nitrate response regulator NarL.
      The multiplicity of FNR factors in P. stutzeri underlines the versatility of the
      FNR scaffold to serve for transcriptional regulation directed at anaerobic or
      nitrate-activated metabolic processes.

PMID- 10209744
TI  - Listeriolysin O-dependent activation of endothelial cells during infection with
      Listeria monocytogenes: activation of NF-kappa B and upregulation of adhesion
      molecules and chemokines.
AB  - The facultative intracellular bacterium Listeria monocytogenes is an invasive
      pathogen that crosses the vascular endothelium and disseminates to the placenta
      and the central nervous system. Its interaction with endothelial cells is crucial
      for the pathogenesis of listeriosis. By infecting in vitro human umbilical vein
      endothelial cells (HUVEC) with L. monocytogenes, we found that wild-type bacteria
      induced the expression of the adhesion molecules (ICAM-1 and E-selectin),
      chemokine secretion (IL-8 and monocyte chemotactic protein-1) and NF-kappa B
      nuclear translocation. The activation of HUVEC required viable bacteria and was
      abolished in prfA-deficient mutants of L. monocytogenes, suggesting that
      virulence genes are associated with endothelial cell activation. Using a genetic
      approach with mutants of virulence genes, we found that listeriolysin O (LLO)
      deficient mutants inactivated in the hly gene did not induce HUVEC activation, as
      opposed to mutants inactivated in the other virulence genes. Adhesion molecule
      expression, chemokine secretion and NF-kappa B activation were fully restored by
      a strain of Listeria innocua transformed with the hly gene encoding LLO. The
      relevance in vivo of endothelial cell activation for listerial pathogenesis was
      investigated in transgenic mice carrying an NF-kappa B-responsive lacZ reporter
      gene. NF-kappa B activation was visualized by a strong lacZ expression in
      endothelial cells of capillaries of mice infected with a virulent haemolytic
      strain, but was not seen in those infected with a non-haemolytic isogenic mutant.
      Direct evidence that LLO is involved in NF-kappa B activation in transgenic mice
      was provided by injecting intravenously purified LLO, thus inducing stimulation
      of NF-kappa B in endothelial cells of blood capillaries. Our results demonstrate
      that functional listeriolysin O secreted by bacteria contributes as a potent
      inflammatory stimulus to inducing endothelial cell activation during the
      infectious process.

PMID- 10209745
TI  - Cell surface protease PRT1 identified in the fungal pathogen Pneumocystis
      carinii.
AB  - The subtelomeric regions of the chromosomes of many organisms contain gene
      families that allow adaptation to a changing environment. In a number of
      parasites, these subtelomeric gene families encode cell surface proteins that
      undergo antigenic variation. Proteases are another important virulence
      determinant in pathogenic microorganisms. We report the localization of the PRT1
      protease of the pathogenic fungus Pneumocystis carinii sp. f. carinii, encoded by
      a subtelomeric gene family, to the cell surface of both the trophozoite and the
      cyst phase of the organism. Using anti-PRT1 antiserum, we demonstrated
      specificity to P. carinii sp. f. carinii in sections of infected rat lungs and,
      using immunofluorescence, we showed that the PRT1 protease has the characteristic
      distribution of a surface protein. The anti-PRT1 antiserum showed cross
      reactivity with a number of P. carinii sp. f. carinii proteins migrating between
      185 kDa and 28 kDa, the majority migrating between 42 kDa and 52 kDa, a region
      that has been shown by serological studies to contain important immunodominant P.
      carinii proteins. Cross-reactivity was also observed with P. carinii sp. f.
      hominis proteins. We have also cloned a portion of the catalytic domain of PRT1
      from P. carinii sp. f. hominis, P. carinii sp. f. muris and P. carinii sp. f.
      rattus. Our data suggest that the PRT1 protease plays an important role in the
      pathogenicity of P. carinii.

PMID- 10209746
TI  - Modelling in Escherichia coli of mutations in mitoribosomal protein S12: novel
      mutant phenotypes of rpsL.
AB  - The rpsL gene of Escherichia coli encodes the highly conserved rps12 protein of
      the ribosomal accuracy centre. We have used the E. coli gene to model the
      phenotypic effects of specific substitutions found in the mitochondrial gene for
      rps12. Variants created by in vitro mutagenesis were tested in two different
      plasmid vector systems, in both streptomycin-sensitive and streptomycin-resistant
      hosts. A substitution with respect to eubacterial rps12 (K87-->Q), found in all
      metazoan and fungal mitochondrial orthologues thus far studied, is associated
      with low-level resistance to streptomycin and a modest (15%) drop in
      translational elongation rate, but without significant effects on translational
      accuracy. An amino-acid replacement at a highly conserved leucine residue (L56-
      >H), associated with the phenotype of sensitivity to mechanical vibration and
      hemizygous female lethality in Drosophila, creates a functionally inactive but
      structurally stable protein that is not assembled into ribosomes. The presence in
      the cell of the mutant, but not wild-type, rpsL greatly downregulates the level
      of a prominent polypeptide of approximately 50 kDa. These results indicate novel
      structure-function relationships in rps12 genes affecting translational function,
      ribosome assembly and drug sensitivity, and indicate a novel regulatory pathway
      that may influence ribosome biogenesis.

PMID- 10209747
TI  - Amino acid residue Ala-62 in the FimH fimbrial adhesin is critical for the
      adhesiveness of meningitis-associated Escherichia coli to collagens.
AB  - Adhesion of meningitis-associated Escherichia coli O18acK1H7 to collagens was
      characterized. The E. coli strain IHE 3034 adhered to type IV and type I
      collagens but not to type III collagen immobilized on glass. Collagens lack
      terminal mannosyl units, yet the bacterial adhesion was completely abolished in
      the presence of alpha-methyl-D-mannoside. A cat cassette was introduced into the
      filmA gene of IHE 3034, and the resulting mutant strain IHE 3034-2 failed to
      adhere to collagens. In contrast, insertion of a Gm cassette into the sfaA gene
      of IHE 3034, encoding the S-fimbrillin, had no significant effect on the
      adhesiveness. The fim cluster from IHE 3034 was cloned and expressed in trans in
      the fimA::cat mutant strain IHE 3034-2. The complemented strain IHE 3034-2(pRPO
      1) exhibited adhesiveness to type IV and type I collagens, confirming the
      function of the type 1 fimbria in the adhesion. We have previously shown that the
      type 1 fimbria from E. coli K-12 strain PC31 does not confer bacterial
      adhesiveness to collagens. The fimH genes from E. coli IHE 3034 as well as from
      PC31 were expressed in the fimH-null strain MS4. The FimH from IHE 3034
      potentiated collagen adherence, whereas the FimH from PC31 was inactive. Sequence
      comparison of fimH from IHE 3034 and PC31 revealed five amino-acid differences in
      the predicted mature FimH proteins: at residues 27, 62, 70, 78 and 201. Each of
      these residues in the IHE 3034-FimH were individually substituted to the
      corresponding amino acid in the PC31-FimH. The substitution S62-->A completely
      abolished collagen adhesiveness. The reverse substitution A62-->S in the PC31
      FimH as well as in the FimH from another E. coli strain induced collagen
      adhesiveness to the level seen with IHE 3034-FimH. Out of nine fimH genes
      analysed from isolates of E. coli, collagen adhesiveness as well as alanine at
      position 62 in FimH were found only in two O18acK1H7 isolates with the isoenzyme
      profile ET type 1. Our results demonstrate that the amino-acid residue Ala-62 in
      the FimH lectin is critical for the adhesion to collagens by a highly virulent
      clonal group of E. coli.

PMID- 10209748
TI  - Environmental regulation of Salmonella pathogenicity island 2 gene expression.
AB  - The enteric pathogen Salmonella typhimurium co-ordinates the expression of
      virulence determinants in response to environmental cues from the host organism.
      S. typhimurium possesses Salmonella pathogenicity island 2 (SPI2), a large
      virulence locus encoding a type III secretion system for virulence determinants
      required for systemic infections and accumulation inside host cells. We have
      generated transcriptional fusions to SPI2 genes to analyse expression and used
      antibodies against recombinant SPI2 proteins to monitor levels of SPI2 proteins
      under various conditions. Here, we demonstrate that SPI2 gene expression is
      induced by Mg2+ deprivation and phosphate starvation. These conditions are likely
      to represent the environmental cues encountered by S. typhimurium inside the
      phagosome of infected host cells. The induction of SPI2 gene expression is
      modulated by the global regulatory system PhoPQ and is dependent on SsrAB, a two
      component regulatory system encoded by SPI2.

PMID- 10209749
TI  - The assembly and migration of SeqA-Gfp fusion in living cells of Escherichia
      coli.
AB  - SeqA protein, which binds to hemi-methylated GATC sequences of DNA, is localized
      to discrete fluorescent foci in wild-type Escherichia coli cells. In this work,
      we observed cellular localization of the SeqA-Gfp fusion in living cells. SeqA
      Gfp was localized to a discrete focus or foci in wild-type and seqA null mutant
      cells, but the fusion was dispersed in the whole cell in dam null mutant cells
      lacking Dam methyltransferase. These results were consistent with the previous
      description of the localization of SeqA by immunofluorescence microscopy. Time
      lapse experiments revealed that duplicated SeqA-Gfp foci migrated rapidly in
      opposite directions. Flow cytometry demonstrated that the fusion restored
      synchronous replication of chromosomal DNA from multiple origins in seqA null
      mutant cells, indicating that SeqA-Gfp is biologically active.
      Immunoprecipitation of the fusion from cell extracts using anti-Gfp antibody
      indicated that the fusion was assembled with the wild-type SeqA protein.

PMID- 10209750
TI  - Escherichia coli nusG mutations that block transcription termination by coliphage
      HK022 Nun protein.
AB  - The Escherichia coli nusG gene product is required for transcription termination
      by phage HK022 Nun protein at the lambda nutR site in vivo. We show that it is
      also essential for Nun termination at lambda nutL. Three recessive mis-sense nusG
      mutations have been isolated that inhibit termination by Nun at lambda nutR. The
      mutations are ineffective in a lambda pL nutL fusion, even when lambda nutR
      replaces lambda nutL. The mutant strains support lambda growth, indicating that
      lambda N antitermination activity is not impaired. Transcription arrest by Nun in
      vitro is stimulated by NusG protein at both lambda nutR and lambda nutL. Mutant
      NusG protein fails to enhance transcriptional arrest by Nun at either site. The
      mutant protein, like the wild-type protein, suppresses transcriptional pausing by
      RNA polymerase and stimulates Rho-dependent termination. These results imply that
      the role of NusG in Nun termination may be distinct from its roles in other
      transcription reactions.

PMID- 10209751
TI  - VirE1 is a specific molecular chaperone for the exported single-stranded-DNA
      binding protein VirE2 in Agrobacterium.
AB  - Agrobacterium tumefaciens induces tumours on plants by transferring a
      nucleoprotein complex, the T-complex, from the bacterium to the plant cell. The T
      complex consists of a single-stranded DNA (ssDNA) segment, the T-DNA, and VirD2,
      an endonuclease covalently attached to the 5' end of the T-DNA. A type IV
      secretion system encoded by the virB operon and virD4 is required for the entry
      of the T-complex and VirE2, a ssDNA-binding protein, into plant cells. The VirE1
      protein is specifically required for the export of the VirE2 protein, as
      demonstrated by extracellular complementation and tumour formation. In this
      report, using a yeast two-hybrid system, we demonstrated that the VirE1 and VirE2
      proteins interact and confirmed this interaction by in vitro binding assays.
      Although VirE2 is a ssDNA-binding protein, addition of ssDNA into the binding
      buffer did not interfere with the interaction of VirE1 and VirE2. VirE2 also
      interacts with itself, but the interaction between VirE1 and VirE2 is stronger
      than the VirE2 self-interaction, as measured in a lacZ reporter gene assay. In
      addition, the interaction of VirE2 with itself is inhibited by VirE1, indicating
      that VirE2 binds VirE1 preferentially. Analysis of various virE2 deletions
      indicated that the VirE1 interaction domain of VirE2 overlaps the VirE2 self
      interaction domain. Incubation of extracts from Escherichia coli overexpressing
      His-VirE1 with the extracts of E. coli overexpressing His-VirE2 increased the
      yield of His-VirE2 in the soluble fraction. In a similar purified protein
      solubility assay, His-VirE1 increased the amount of His-VirE2 partitioning into
      the soluble fraction. In Agrobacterium, VirE2 was undetectable in the soluble
      protein fraction unless VirE1 was co-expressed. When urea was added to solubilize
      any large protein aggregates, a low level of VirE2 was detected. These results
      indicate that VirE1 prevents VirE2 from aggregating, enhances the stability of
      VirE2 and, perhaps, maintains VirE2 in an export-competent state. Analysis of the
      deduced amino acid sequence of the VirE1 protein revealed that the VirE1 protein
      shares a number of properties with molecular chaperones that are involved in the
      transport of specific proteins into animal and plant cells using type III
      secretion systems. We suggest that VirE1 functions as a specific molecular
      chaperone for VirE2, the first such chaperone linked to the presumed type IV
      secretion system.

PMID- 10209752
TI  - Protonmotive force, ExbB and ligand-bound FepA drive conformational changes in
      TonB.
AB  - TonB couples the cytoplasmic membrane protonmotive force (pmf) to active
      transport across the outer membrane, potentially through a series of
      conformational changes. Previous studies of a TonB transmembrane domain mutant
      (TonB-delta V17) and its phenotypical suppressor (ExbB-A39E) suggested that TonB
      is conformationally sensitive. Here, two new mutations of the conserved TonB
      transmembrane domain SHLS motif were isolated, TonB-S16L and -H20Y, as were two
      new suppressors, ExbB-V35E and -V36D. Each suppressor ExbB restored at least
      partial function to the TonB mutants, although TonB-delta V17, for which both the
      conserved motif and the register of the predicted transmembrane domain alpha
      helix are affected, was the most refractory. As demonstrated previously, TonB can
      undergo at least one conformational change, provided both ExbB and a functional
      TonB transmembrane domain are present. Here, we show that this conformational
      change reflects the ability of TonB to respond to the cytoplasmic membrane proton
      gradient, and occurs in proportion to the level of TonB activity attained by
      mutant-suppressor pairs. The phenotype of TonB-delta V17 was more complex than
      the -S16L and -H20Y mutations, in that, beyond the inability to be energized
      efficiently, it was also conditionally unstable. This second defect was evident
      only after suppression by the ExbB mutants, which allow transmembrane domain
      mutants to be energized, and presented as the rapid turnover of TonB-delta V17.
      Importantly, this degradation was dependent upon the presence of a TonB-dependent
      ligand, suggesting that TonB conformation also changes following the energy
      transduction event. Together, these observations support a dynamic model of
      energy transduction in which TonB cycles through a set of conformations that
      differ in potential energy, with a transition to a higher energy state driven by
      pmf and a transition to a lower energy state accompanying release of stored
      potential energy to an outer membrane receptor.

PMID- 10209753
TI  - Autoregulation of lactose uptake through the LacY permease by enzyme IIAGlc of
      the PTS in Escherichia coli K-12.
AB  - Bacterial growth on one or more carbon sources requires careful control of the
      uptake and metabolism of these carbon sources. In Escherichia coli, the
      phosphorylation state of enzyme IIAGlc of the phosphoenolpyruvate:carbohydrate
      phosphotransferase system (PTS) is involved in this control in two ways. The
      unphosphorylated form of IIAGlc causes 'inducer exclusion', the inhibition of
      uptake of a number of non-PTS carbon sources, including lactose uptake by the
      lactose permease. The phosphorylated form of enzyme IIAGlc probably activates
      adenylate cyclase. In cells growing on lactose, enzyme IIAGlc was approximately
      50% dephosphorylated, suggesting that lactose could inhibit its own uptake. This
      inhibition could be demonstrated by comparing lactose uptake rates in the wild
      type strain and in a mutant in which the lactose carrier was insensitive to
      inducer exclusion. In this deregulated mutant strain, lactose was consumed much
      faster, and large amounts of glucose were excreted. It was shown that enzyme
      IIAGlc was dephosphorylated more strongly and that the cAMP level was lower in
      the mutant, most probably causing the observed decrease in lac expression level.
      When the lac expression level in the mutant strain was increased to that of the
      parent strain by adding exogenous cAMP, growth on lactose was slower, suggesting
      that enzyme IIAGlc-mediated inhibition of lactose uptake and downregulation of
      the lac expression level protected the cells against excessive lactose influx. An
      even stronger increase in the lac expression level in a mutant lacking enzyme
      IIAGlc caused complete growth arrest. We conclude that the autoregulatory
      mechanism that controls lactose uptake is an important mechanism for the cells in
      adjusting the uptake rate to their metabolic capacity.

PMID- 10209754
TI  - The contribution of the O-glycosylated protein Pir2p/Hsp150 to the construction
      of the yeast cell wall in wild-type cells and beta 1,6-glucan-deficient mutants.
AB  - The cell wall of yeast contains a major structural unit, consisting of a cell
      wall protein (CWP) attached via a glycosylphosphatidylinositol (GPI)-derived
      structure to beta 1,6-glucan, which is linked in turn to beta 1, 3-glucan. When
      isolated cells walls were digested with beta 1,6-glucanase, 16% of all CWPs
      remained insoluble, suggesting an alternative linkage between CWPs and structural
      cell wall components that does not involve beta 1,6-glucan. The beta 1,6
      glucanase-resistant protein fraction contained the recently identified GPI
      lacking, O-glycosylated Pir-CWPs, including Pir2p/Hsp150. Evidence is presented
      that Pir2p/Hsp150 is attached to beta 1,3-glucan through an alkali-sensitive
      linkage, without beta 1,6-glucan as an interconnecting moiety. In beta 1,6-glucan
      deficient mutants, the beta 1,6-glucanase-resistant protein fraction increased
      from 16% to over 80%. This was accompanied by increased incorporation of
      Pir2p/Hsp150. It is argued that this is part of a more general compensatory
      mechanism in response to cell wall weakening caused by low levels of beta 1,6
      glucan.

PMID- 10209755
TI  - The identification of a new family of sugar efflux pumps in Escherichia coli.
AB  - Using a functional cloning strategy with an Escherichia coli genomic plasmid
      library, we have identified a new family of sugar efflux proteins with three
      highly homologous members in the E. coli genome. In addition, two open reading
      frames, one present in Yersinia pestis and the other in Deinococcus radiodurans,
      appear to encode closely related proteins. An in vitro transport assay using
      inside-out membrane vesicles prepared from overproducing strains was used to
      demonstrate that members of this new family can efflux [14C]-lactose. As sugar
      efflux phenomena have been reported previously in several bacterial species
      including E. coli, the identification of a new family of sugar efflux proteins
      may help to reveal the physiological role of sugar efflux in metabolism. It is
      proposed that the E. coli members of this family, whose functions were previously
      unknown, be given the gene family designation SET for sugar efflux transporter.

PMID- 10209757
TI  - 25th International Conference on the Biology of the Myxobacteria.

PMID- 10209756
TI  - Recruitment of ZipA to the division site by interaction with FtsZ.
AB  - ZipA is an essential cell division protein in Escherichia coli that is recruited
      to the division site early in the division cycle. As it is anchored to the
      membrane and interacts with FtsZ, it is a candidate for tethering FtsZ filaments
      to the membrane during the formation of the Z ring. In this study, we have
      investigated the requirements for ZipA localization to the division site. ZipA
      requires FtsZ, but not FtsA or FtsI, to be localized, indicating that it is
      recruited by FtsZ. Consistent with this, apparently normal Z rings are formed in
      the absence of ZipA. The interaction between FtsZ and ZipA occurs through their
      carboxy-terminal domains. Although a MalE-ZipA fusion binds to FtsZ filaments, it
      does not affect the GTPase activity or dynamics of the filaments. These results
      are consistent with ZipA acting after Z ring formation, possibly to link the
      membrane to FtsZ filaments during invagination of the septum.

PMID- 10209758
TI  - Liver regeneration after partial hepatectomy is non-uniform: flow cytometric
      bromodeoxyuridine incorporation and cell cycle studies in a porcine model.
AB  - The rate of hepatocyte regeneration at different anatomical locations of the
      remnant liver after partial hepatectomy was assessed in porcine hepatocytes by
      bromodeoxyuridine (BrdUr) incorporation and cell cycle kinetics using flow
      cytometric analysis. Partial hepatectomy was performed in five Yorkshire pigs. A
      single intravenous injection of BrdUr at 50 mg/kg was administered on the 2nd
      post-operative day and the animals were sacrificed 1 h later. The remnant liver
      tissue was harvested and divided into four equal zones, from the liver periphery
      towards the surgical cut-edge. Biopsy samples were obtained from the centre of
      each of these zones and similarly from identical anatomical locations in two
      control pigs that had undergone sham surgery. Hepatocyte nucleus suspension was
      prepared, double labelled with anti-BrdUr and propidium iodide and analysed by a
      flow cytometer. The cells in S-phase was used as the parameter to measure the
      regeneration status. A gradient increase in S-phase from the periphery to the cut
      edge was observed in all five pigs that had undergone partial hepatectomy. The
      percentage of S-phase cells in all four zones from the hepatectomy group was
      significantly higher when compared with that in the controls. Liver regeneration
      after partial hepatectomy was not uniform but was greatest adjacent to the
      surgical cut edge and decreased towards the periphery of the liver.

PMID- 10209759
TI  - Antithrombin III prevents 60 min warm intestinal ischemia reperfusion injury in
      rats.
AB  - We investigated the effect of antithrombin III on 60 min warm intestinal ischemia
      reperfusion (IR) injury in rats. Sprague-Dawley rats, weighing 220-250 g, were
      divided into three groups: group 1 sham-operated group (no IR injury, n = 8),
      group 2 ischemic control group (control, Ringer's lactate infused, n = 8), group
      3 Antithrombin III treated group (250 U/kg before ischemia, n = 8). Intestinal
      ischemia was induced in rats by occluding the superior mesenteric artery for 60
      min. Malondialdehyde (MDA) levels, myeloperoxidase activity (MPO) and mucosal
      damage were investigated after 120 min reperfusion. Elevated MDA levels and MPO
      activity and severe histopathological damage were observed in the control group
      compared with the sham group (P < 0.05). Decreased MDA levels and MPO activity
      and less histopathological damage were detected in group 3 compared with the
      control group (P < 0.05). Accumulation of lipid peroxidation products and
      neutrophils in mucosal tissues were significantly inhibited by antithrombin III
      treatment. We conclude that treatment with antithrombin III before intestinal
      ischemia prevents histological damage in rats.

PMID- 10209760
TI  - The effect of continuously applied cyclic mechanical loading on the fibronectin
      metabolism of articular cartilage explants.
AB  - Articular cartilage serves primarily as a load-bearing material able to regulate
      its own metabolic activity in response to the mechanical stimuli applied.
      Fibronectin plays a critical role in the organization and function of the
      cartilage extracellular matrix. The purpose of this study was to investigate
      systematically the effect of load magnitude, frequency and duration of loading on
      the synthesis, content and release of fibronectin and proteins by mature bovine
      articular cartilage explants using a novel mechanical loading system. Increasing
      the load magnitude, as well as the duration of loading, inhibited the synthesis
      and content of fibronectin and proteins; the fibronectin synthesis was more
      specifically affected than the overall protein synthesis indicating that
      fibronectin is more responsive to pressure than synthesis of other proteins.
      Reducing the load frequency did not modulate the inhibitory effect of a given
      cyclic stress on synthesis and content of fibronectin and proteins even though
      explants were more compressed. The release of endogenous fibronectin was
      significantly reduced independent of the applied loading protocols when compared
      with unloaded controls. This study demonstrates that the magnitude and the
      duration of loading influences the degree of inhibition of fibronectin and
      protein synthesis, while loaded explants possess an elevated but limited capacity
      to bind fibronectin. Compared with other studies, our present results show that
      the applied load function in particular has a profound effect on the metabolism
      of chondrocytes.

PMID- 10209761
TI  - Simulation of lung lesions for validating the sonography of the flooded lung.
AB  - The quality of sonography of a unilaterally flooded lung needs to be validated on
      lesions of different echogenicity, size and subpleural position. Lesions were
      simulated in 12 young pigs with three different methods. After transbronchial
      (method 1) or transpleural puncture (method 2), diverse substances were injected
      into the lung. After 4 weeks, the thorax was opened and the lung flooded for the
      sonographic location of the lesions. In method 3, pulmonary lesions were
      simulated in an acute experiment after thoracotomy by transpleural injection or
      by filling of a Fogarty catheter balloon and were located sonographically.
      Transbronchial injection of alcohol invariably led to subsegment atelectasis.
      Only 25% of thoracoscopically controlled transpleural injections produced focal
      lesions in experiments in which the animals survived. Representative lesions were
      found only after alcohol injections. Transpleural injection of blood or a
      blood/Echovist suspension (method 3) simulated isoechogenic or echo-rich lesions
      with indistinct boundaries. By filling a Fogarty catheter balloon with saline
      solution or Echovist suspension, we succeeded in simulating echo-free or echo
      rich lesions with smooth contours, located in different subpleural depths. After
      unilateral lung flooding, sonography successfully detected the locations of all
      these lesions and revealed their correlation with functional structures.
      Sonography of the flooded lung might be helpful in the intraoperative location of
      lesions, especially in the context of video-assisted thoracoscopic surgery.

PMID- 10209762
TI  - The effects of intraperitoneal piroxicam and low molecular weight heparin in
      prevention of adhesion reformation in rat uterine horn.
AB  - Our objective was to determine the effectiveness of intraperitoneal single dose
      piroxicam and low molecular weight heparin (LMWH) on prevention of adhesion
      reformation in the rat uterine horn. This study was carried out in the Surgical
      Research Laboratory, at Erciyes University. A standard lesion was created by
      unipolar electrocautery in 72 uterine horns of 36 female Wistar-Albino rats.
      After 2 weeks, adhesion formation scores were determined and adhesiolysis was
      performed in the second-look laparotomy. Animals were then randomly assigned into
      three groups. Each group contained 12 animals: group 1 was the control group
      where no adjuvant was given; in group 2, 1 ml 50 U Axa IC/ml solution LMWH was
      applied to the horns postoperatively, and in group 3, 1 ml 2 mg/ml piroxicam
      solution was applied to the horns after adhesiolysis. Two weeks later the rats
      were killed and adhesion reformation was evaluated. The number of horns with
      adhesion formation and the cumulative scores were not significantly different
      among the three groups in the second-look laparotomies, but after third-look
      laparotomies, the number of horns with adhesion reformation, after calculating
      the extent, severity and total scores of adhesion reformation, was found to be
      significantly less in LMWH and piroxicam groups than in the control group. Also,
      the effectiveness of piroxicam was significantly greater in all scores of
      adhesion reformation than LMWH was. In conclusion, both LMWH and piroxicam doses
      reduce adhesion reformation in the rat uterine horn, but the effectiveness of
      piroxicam is significantly greater than that of LMWH.

PMID- 10209763
TI  - Organ growth and lung maturation in rabbit fetuses.
AB  - The rabbit fetus is one of the most commonly used animal models in experimental
      studies investigating fetal organ development. However, there is no detailed
      information about normal growth of organs of rabbit fetuses in English language
      literature. Fetal rabbits were studied in the second half of gestation between
      18th and 30th days. Amniotic fluid volume, body mass (BM), lung, heart and liver
      masses (LM, HM, LiM), lung and thorax volumes (LV, TV) were determined and LM/BM,
      HM/BM, LiM/BM, TV/BM and LV/TV ratios were calculated. Additionally fetal lungs
      were evaluated histologically, BM, LM, HM, LiM and LV were increased until 27th
      gestational day and then remained unchanged. TV was always increased between 18th
      gestational day and term. The lung maturation was almost completed in the 27th
      28th gestational days. Therefore, BM, LM, HM, LiM and LV are the parameters that
      can be used to evaluate normal fetal growth between 18th and 27th gestational
      days. TV seems to be the predictive parameter for evaluation of normal fetal
      growth during the second half of gestation in rabbit fetuses; 20th and 27th days
      of gestation are more appropriate for experiments to evaluate lung maturation.

PMID- 10209764
TI  - Molecular nature of RAPD markers from Haemophilus influenzae Rd genome.
AB  - Despite the widespread application of the random amplified polymorphic DNA (RAPD)
      technique, there is no experimental evidence of the molecular mechanism of random
      amplification starting from a complex template. To investigate this mechanism, we
      cloned and sequenced 23 selected RAPD bands amplified from Haemophilus influenzae
      Rd genomic DNA using eight decamer primers different in GC content and/or
      nucleotide sequence. As the whole genome sequence of H. influenzae Rd has been
      reported, the exact nucleotide sequence of each primer-template annealing site
      was identified. Results showed that, on an average, a homology of eight base
      pairs was involved in priming events and that the number of nonhomologous base
      pairings declined exponentially from the 5' end of the primer to its 3' end. The
      interaction between the primer and the template DNA was stabilized by the
      formation of secondary structures, and a perfect match of the 3' terminal region
      of the primer was not necessary for successful amplification. The complexity of
      the annealing process suggested that, in the studied reaction conditions, many
      primer-template annealing sites were extended in the first cycles and that
      differences in the efficiency of priming and replication processes led to
      amplification of RAPD fragments. Moreover, the distribution of the amplified
      regions on the H. influenzae chromosome was analyzed.

PMID- 10209765
TI  - Yarrowia lipolytica cell wall architecture: interaction of Ywp1, a mycelial
      protein, with other wall components and the effect of its depletion.
AB  - Linkages of Ywp1 to other components of the Yarrowia lipolytica mycelial cell
      wall were studied by extraction with beta-mercaptoethanol and zymolyase (a beta
      glucanase complex) and by the use of rabbit polyclonal antibody preparation
      raised against Ywp1. Ywp1 complexed with an N-glycosylated cell wall protein(s)
      to form supramolecular complexes through disulphide bridges (extractable with
      beta-mercaptoethanol) or bonded to beta-1,3-glucan (extractable with zymolyase).
      The lack of a specific morphological phenotype when YWP1 was knocked out by gene
      disruption might indicate that other proteins present in the cell wall of Y.
      lipolytica compensated for its loss. In this mutant, the electrophoretic pattern
      of proteins, detected with polyclonal antibodies against the entire cell wall,
      was different from that obtained with the parental strain, but sensitivity to
      calcofluor white, zymolyase and chitinase did not change. Quantitative analysis
      of fluorescence emitted by cells in the presence of fluorescent wheat germ
      agglutinin (FITC-WGA) indicated that chitin was organized in the cell wall of the
      mutant cells in a form different from that in the parental strain.

PMID- 10209767
TI  - Effect of growth temperature on the biosynthesis of cell wall proteins from
      Bifidobacterium globosum.
AB  - Seventy strains of Bifidobacterium globosum isolated from gastrointestinal tracts
      of different animals were studied. Strains were grown at temperatures ranging
      from 25 to 46.5 degrees C in order to examine changes both in the expression of
      bifidobacterial outer proteins (BIFOPs) and in their hydrophobic properties. It
      was observed that the expression of BIFOPs found on the cell-surface changes
      according to growth temperature, with quantitative and/or qualitative variations.
      Generally speaking, it was observed that BIFOP expression at low-growth
      temperature was considerably attenuated, while at medium- and high-growth
      temperature it increased. Furthermore, at high-growth temperatures, the presence
      of a new common protein was detected in all the strains studied. Cells from B.
      globosum strains grown under different temperature conditions were studied in
      terms of their cellular hydrophobicity properties. At medium-growth temperature,
      the cell hydrophobicity was strictly correlated with BIFOP expression, while at
      low and high-growth temperatures, the presence of BIFOP only partially influenced
      the hydrophobic features.

PMID- 10209766
TI  - Pattern of changes in the activity of enzymes of GDP-D-mannuronic acid synthesis
      and in the level of transcription of algA, algC and algD genes accompanying the
      loss and emergence of mucoidy in Pseudomonas aeruginosa.
AB  - The low activity levels of the four GDP-D-mannuronic acid-forming enzymes, even
      in highly alginate-producing strains of Pseudomonas aeruginosa, have made it
      difficult to compare enzyme activities accompanying the loss/acquisition of
      mucoidy. Using optimized conditions, we compared the specific activity of these
      enzymes in three different mucoid P. aeruginosa cystic fibrosis isolates, in
      their nonmucoid spontaneous variants, and in mucoid variants that emerged during
      extended incubation of these nonmucoid forms in acetamide broth. A correlation
      was established between the promptness of emergence of the mucoid forms and the
      differing sensitivity to nutrient-limitation-induced death of the nonmucoid
      compared with the isogenic mucoid population. Consistent with the undetectable
      levels of algD mRNA in nonmucoid forms and with the concept that the step
      catalyzed by the algD-encoded GDP-mannose dehydrogenase (GMD) is a key step in
      control of the alginate pathway, GMD activity was undetectable or showed
      negligible values in nonmucoid variants and correlated with alginate production.
      However, phosphomannose isomerase (PMI), phosphomannomutase (PMM), and GDP
      mannose pyrophosphorylase (GMP) activities in the nonmucoid forms were only
      slightly (40-70%) below the values in the mucoid forms. Nevertheless, no
      transcripts homologous to algA (encoding a bifunctional enzyme that possesses
      both PMI and GMP activities) were detected in the nonmucoid form, and the levels
      of algC (encoding PMM) transcripts, although detectable in the nonmucoid
      variants, were, in general, much higher in the mucoid forms. These apparently
      intriguing observations were cleared up by the identification of two algA
      functional homologues in P. aeruginosa, recently reported by others, and by the
      identification of one algC homologue, in contig225 of the PAO1 genome sequence,
      defining a polypeptide with a deduced amino acid sequence that showed significant
      homology with that of enzymes of the phosphohexomutase family found in databases.
      Results are also consistent with the requirement of PMI, GMP and PMM activities
      for the supply of GDP-D-mannose to (at least) A-band lipopolysaccharide
      synthesis, while GMD channels this precursor into the alginate pathway.

PMID- 10209768
TI  - Molecular characterization of femA from Staphylococcus hominis and Staphylococcus
      saprophyticus, and femA-based discrimination of staphylococcal species.
AB  - The femA gene encodes a protein precursor which plays a role in peptidoglycan
      biosynthesis in Staphylococcus aureus and is also considered as a factor
      influencing the level of methicillin resistance. A femA homologous gene was
      recently characterized in S. epidermidis, entailing the possibility of femA
      phylogenetic conservation in staphylococcal species. Accordingly, we assessed the
      presence of femA homologous genes in S. hominis and S. saprophyticus. Strategy
      for identification relied upon alignment of S. aureus and D. epidermidis femA
      sequences and upon identification of potentially conserved regions.
      Amplifications of portions of the femA genes were performed under permissive
      annealing conditions, by using several sets of primers designed to match the
      consensus regions. DNA sequencing of overlapping PCR fragments led to the
      characterization of the entire femA genes of S. hominis and S. saprophyticus, and
      provided more precise information on the femA start codon for all five species.
      The genomic organization of all these femA genes appeared highly conserved, with
      alternance of homologous and variable regions. On this basis, a consensus
      sequence of the femA gene was defined and interspecies variations were exploited
      to design strategies for staphylococci species-specific identification, including
      multiplex PCR amplification and a reverse hybridization assay.

PMID- 10209769
TI  - Nucleic acid extraction from polluted estuarine water for detection of viruses
      and bacteria by PCR and RT-PCR analysis.
AB  - We describe an extraction protocol for genomic DNA and RNA of both viruses and
      bacteria from polluted estuary water. This procedure was adapted to the molecular
      study of microflora of estuarine water where bacteria and viruses are found free,
      forming low-density biofilms, or intimately associated with organo-mineral
      particles. The sensitivity of the method was determined with seeded samples for
      RT-PCR and PCR analysis of viruses (10 virions/mL), and bacteria (1 colony
      forming unit mL). We report an example of molecular detection of both poliovirus
      and Salmonella in the Seine estuary (France) and an approach to studying their
      association with organo-mineral particles.

PMID- 10209770
TI  - Phenotypic and genetic diversity among Bacillus sphaericus strains isolated in
      Brazil, potentially useful as biological control agents against mosquito larvae.
AB  - Thirty mosquitocidal strains of Bacillus sphaericus isolated from different
      sources and localities in Brazil were characterized phenotypically and
      genetically to determine their relationship. Among the strains tested, 93.3% were
      shown to be resistant to lincomycin, 96.6% to novobiocin, 60% to chloramphenicol
      and all strains were resistant to streptomycin. Resistance to HgCl2, NiSO4.6H2O
      and CuSO4 was observed in 83.3, 86.6 and 100% of the strains, respectively. All
      strains were inhibited by the presence of CoSO4. Tolerance to ethanol and
      variable responses to different amounts of creolin, phenol and xylol was also
      observed. Amplification of DNA of each of 30 isolates using repetitive primers
      allowed the identification of 5 groups of similar strains in BOX-PCR and 8 groups
      in REP-PCR. Using cloned toxin genes from B. sphaericus as probes in
      hybridization studies, 83% of the strains studied hybridized to the bin probe and
      90% to the mtx probe. A comparison of the 30 strains by similarity matrix
      analysis using the data obtained in all approaches used in this study resulted in
      22 groups (16 groups among the 24 high-toxicity strains) at 100% similarity,
      indicating a high degree of diversity among the strains tested. Some of the
      strains studied here, which are resistant to different stress conditions, should
      be considered for further ecological studies.

PMID- 10209771
TI  - Neuromagnetic studies of human auditory cortex function and reorganization.
AB  - Much of our present understanding of sensory processing by the human brain is
      obtained from studies of patients with sensory impairments. Past auditory studies
      have focused strongly on the peripheral mechanisms of hearing disorders, and have
      led to an overuse of stimuli that are good for testing the transfer functions of
      simple acoustic features but are not suitable for understanding the perception of
      complex auditory stimuli or stimulus sequences. Magnetoencephalography (MEG) is a
      non-invasive method for studying how the human brain processes and stores
      auditory information. The long-term groundwork in building up the basic
      understanding of cortical dynamics during various "simple" stimulations now
      allows the use of more complex, real-life-like stimuli, and clinical
      applications.

PMID- 10209773
TI  - Neuroanatomical correlates to central deafness.
AB  - Our research experience with five centrally deaf patients showed that damage to
      various anatomical sites could result in central deafness. This finding was
      contrary to the commonly held notion that both Heschl's gyri must be severely
      damaged to yield central deafness. To discover whether lesions in various brain
      areas could cause central deafness, we reviewed 33 cases of central deafness
      reported in the literature which had sufficient radiological data to determine
      the anatomical regions involved. Both Heschl's gyri were involved in the majority
      of these cases, but there were definite exceptions. In these exceptional cases of
      central deafness, subcortical areas were involved (usually the internal capsule),
      as was the insula. Overall findings are discussed and recommendations are offered
      for the future study of centrally deaf patients.

PMID- 10209772
TI  - Speech sound perception and learning: biologic bases.
AB  - Historically, auditory research has focused predominantly on how relatively
      simple acoustic signals are represented in the neuronal responses of the auditory
      periphery. However, in order to understand the neurophysiology underlying speech
      perception, the ultimate objective is to discover how speech sounds are
      represented in the central auditory system and to relate that representation to
      the perception of speech as a meaningful acoustic signal. This paper reviews
      three areas pertaining to the central auditory representation of speech: (1) the
      differences in neural representation of speech sounds at different levels of the
      auditory system, (2) the relation between the representation of sound in the
      auditory pathway and the perception/misperception of speech, and (3) the
      plasticity of speech-sound neural representation and speech perception.

PMID- 10209774
TI  - Central auditory processing, MRI morphometry and brain laterality: applications
      to dyslexia.
AB  - We review data from our laboratory related to a view of dyslexia as a biological
      disorder, or deficit, caused by both structural and functional brain
      abnormalities. The review is focused on central auditory processing in dyslexia,
      and the possibility that impairments in the auditory or acoustic features of the
      phonological code may be at the heart of the impairments seen in dyslexia. Three
      methodological approaches by which to investigate central auditory processing
      deficits are outlined: dichotic listening (DL) to consonant-vowel syllables;
      magnetic resonance imaging (MRI), and the use of event-related potentials (ERPs).
      Consonant-vowel syllable DL is a technique for probing the functional status of
      phonological processing areas in the superior temporal gyrus, particularly in the
      left hemisphere. MRI is a corresponding structural, or morphological, measure of
      anatomical abnormalities in the same brain region, particularly covering the
      planum temporale area. The ERP technique, and particularly the mismatch
      negativity (MMN) component, reveals cortical dysfunctions in sensory processing
      and memory related to basic acoustic events. For all three approaches, the
      dyslexic children were seen to differ from their control counterparts, including
      absence of modulation of the right ear advantage (REA), in DL through shifting of
      attention, smaller left-sided planum temporale asymmetry, and prolonged latency
      in the MMN ERP complex, particularly in the time-deviant stimulus condition.

PMID- 10209775
TI  - Dichotic speech tests.
AB  - When central auditory dysfunction is present, ability to understand speech in
      difficult listening situations can be affected. To study this phenomenon,
      dichotic speech tests were performed with test material in the Swedish language.
      Digits, spondees, sentences and consonant-vowel syllables were used as stimuli
      and the reporting was free or directed. The test material was recorded on CD. The
      study includes a normal group of 30 people in three different age categories; 11
      years, 23-27 years and 67-70 years. It also includes two different groups of
      subjects with suspected central auditory lesions; 11 children with reading and
      writing difficulties and 4 adults earlier exposed to organic solvents. The
      results from the normal group do not show any differences in performance due to
      age. The children with reading and writing difficulties show a significant
      deviation for one test with digits and one test with syllables. Three of the four
      adults exposed to solvents show a significant deviation from the normal group.

PMID- 10209776
TI  - Non-linear signal processing in digital hearing aids.
AB  - Three different non-linear digital signal processing algorithms were developed;
      LinEar, DynEar and RangeEar. All three provided individual frequency shaping via
      a seven-band low-power filterbank and compression in two channels. RangeEar and
      DynEar used wide dynamic range syllabic compression in the low-frequency (LF)
      channel, while LinEar used compression limiting. In the high-frequency (HF)
      channel, RangeEar used a slow-acting automatic volume control, while DynEar and
      LinEar used compression limiting. Wearable digital signal processing-based
      experimental instruments were used to evaluate the fitting algorithms under real
      world conditions with experienced hearing aid users. Evaluation included
      laboratory testing of speech recognition in noise and questionnaires on sound
      quality ratings. Results did not indicate one general good-for-all algorithm, but
      different algorithms resulting in preference and performance depending on the
      hearing loss configuration. Preference for any of the new algorithms could be
      predicted based on auditory dynamic range measurements. It was hypothesized that
      the different preferences were affected by different susceptibility to masking of
      HF sounds by amplified LF sounds.

PMID- 10209777
TI  - Clinical assessment of modern hearing aids.
AB  - The increasing complexity of the non-linear signal processing of modern hearing
      aids makes the use of clinical assessment of hearing aid benefit more and more
      important. The paper discusses the general structure of such studies with regard
      to choice of test subjects, reference hearing aids and the advantage of double
      blind and cross-over design. Assessment should contain at least the three
      dimensions: perceived hearing aid benefit (preferably including perceived sound
      quality and preference between test and reference aids), speech recognition in
      noise, and electroacoustic verification by means of real-ear measurements.

PMID- 10209778
TI  - Speech tests as measures of outcome.
AB  - Speech tests comprise an important and integral part of any assessment of the
      effectiveness of intervention for hearing disability and handicap. Particularly
      when considering hearing aid services for adult listeners, careful consideration
      has to be given to the particular form and application of inferences drawn from
      speech identification procedures if erroneous conclusions are to be avoided. It
      is argued that four such components relate to the statistical properties and
      discriminatory leverage of speech identification procedures, the choice of
      presentation level and conditions in regard to the auditory environment
      experienced by hearing-impaired clients, the extent to which speech tests based
      on segmental intelligibility provide appropriate information in relationship to
      perceived disabilities and handicaps, and the ways in which speech identification
      procedures to evaluate the potential benefits of signal-processing schemes for
      hearing aids are dependent upon sufficient listening experiences. Data are drawn
      from the literature to illuminate these points in terms of application in
      clinical practice and clinical evaluation exercises, and also with regard to
      future research needs.

PMID- 10209779
TI  - Use of patient-specific estimates in patient evaluation and rehabilitation.
AB  - For a number of years we have been using open-ended questionnaires in the
      assessment of hearing disability and handicap, tinnitus complaint behaviour
      together with shortcomings and benefits of various rehabilitative interventions.
      More recently we have applied this approach to positive experiences reported by
      adults who have developed a hearing impairment and to the use of silence or
      social withdrawal as a communication tactic. In addition, we have asked
      individuals to rate the magnitude of each of their listed disabilities,
      handicaps, shortcomings, etc., on a scale to provide a qualitative assessment of
      each of these elements important to the individual. Such a procedure can be
      repeated after the intervention to measure changes in such estimates. This
      approach can thus highlight for the therapist, those elements of the patients'
      problems which are being well or poorly addressed and hence help them to
      concentrate their effort on the latter. Results obtained using this technique are
      presented and discussed.

PMID- 10209780
TI  - Reflections on evaluative research in audiological rehabilitation.
AB  - Changes in service delivery triggered by current conceptualizations of
      rehabilitation require an accompanying paradigm shift in the approaches used to
      evaluate the effectiveness of intervention programs in audiological
      rehabilitation. The present article outlines three fundamental principles of
      contemporary rehabilitative audiology that have implications concerning the way
      that audiological rehabilitation services should be conceived and dispensed, as
      well as the way in which comprehensive evaluative research investigations should
      be designed and conducted. Traditional treatment efficacy paradigms used to
      assess the effectiveness of intervention programs in rehabilitative audiology are
      critiqued. Finally, factors that should guide the development of comprehensive
      evaluative research paradigms which are consistent with current models of
      intervention in audiological rehabilitation are outlined.

PMID- 10209782
TI  - Memory for language in deaf adults and children.
AB  - Cognitive psychologists have known for a long time that language and memory are
      intimately related in people who can hear. Why should the situation be any
      different for deaf children and deaf adults? This article considers the results
      of previous studies and some new findings in examining the possible impact of
      spoken language and sign language fluencies/preferences on the structure and
      process of memory in deaf individuals. Current evidence suggests that there are
      some differences in the organization of long-term memory in deaf as compared to
      hearing people, but no one has yet demonstrated such differences to be so large
      that they qualitatively or quantitatively affect learning in any real sense. In
      contrast, there is now abundant evidence to suggest that variation in spoken
      language abilities have a direct impact on memory span and perhaps on working
      memory more generally. These findings are discussed in terms of their
      implications for the education of students who are deaf or hard of hearing.

PMID- 10209781
TI  - Speechreading: advances in understanding its cortical bases and implications for
      deafness and speech rehabilitation.
AB  - Some cortical correlates of (silent) speechreading in normal people are described
      and contextualized with respect both to seeing faces and to hearing speech. Some
      preliminary work with two people with abnormal language is described, as are some
      findings concerning evoked responses to seen speech. Superior temporal cortical
      areas (classical 'speech association' areas) are strongly and specifically
      implicated in seeing silent speech. In addition, primary auditory cortex can be
      activated by silent speechreading in hearing people. The implications of these
      findings for deafness and for issues of compensation and plasticity are outlined.

PMID- 10209783
TI  - Phonological deterioration in adults with an acquired severe hearing impairment.
AB  - The study examined the phonological processing skills in a group of adults who
      have acquired a severe hearing loss in adult life. These severely hearing
      impaired individuals performed at a significantly lower level on the rhyme
      judgement tasks and the letter span task, but on a par with the control group on
      other cognitive tests. A correlation analysis showed that duration of hearing
      loss is negatively related to performance on the rhyme judgement tasks and letter
      span task. The results indicate that the phonological processing skills in
      individuals who have acquired a severe hearing loss in adult life deteriorates.
      The results are discussed with respect to theoretical and clinical implications.

PMID- 10209784
TI  - Cognition as a bridge between signal and dialogue: communication in the hearing
      impaired and deaf.
AB  - This paper is an overview of the research we have carried out at Linkoping
      University on cognitive aspects of visual language processing and related
      communicative forms. In the first section, a cognitive individual difference
      perspective on speechreading is introduced. In the second, compensatory
      perceptual mechanisms are discussed on the basis of behavioral and
      neurophysiological data. The third section addresses further the issue of
      perceptual versus cognitive compensation, and the fourth and fifth sections apply
      a set of cognitive tests based on the concept of working memory for poorly
      specified language input to data on the successes and failures with cochlear
      implants, tactile aids and hearing aids.

PMID- 10209785
TI  - Cognitive diversity in deaf people: implications for communication and education.
AB  - Research and issues related to cognitive diversity in deaf people will be
      reviewed that indicate how the visual-perceptual skills and cognitive processes
      of deaf people may be different from those in hearing people. It is suggested
      that deafness and the use of a sign language may selectively contribute to the
      development of such differences. Implications of the research and its limitations
      for enhancing the communication and educational experiences of deaf people are
      also discussed.

PMID- 10209786
TI  - Communication as social engagement: implications for interactions between deaf
      and hearing persons.
AB  - Communication involves sending and receiving signals. However, it is also a form
      of social engagement. Constraints on communication between deaf and hearing
      persons often result in strained interactions as well as los of "full"
      information. In this paper, a meta-ethnographic approach is used to describe the
      impact of "spoiled" communication on social engagement between deaf and hearing
      persons.

PMID- 10209787
TI  - Hearing impairment, emotions and audiological rehabilitation: a sociological
      perspective.
AB  - Encounters are one of the basic dynamics of society, although this does not imply
      that macro-phenomena do not have ontological status. Encounters involve
      interaction and hence communication, and interaction and communication generate
      emotions. Emotions are of great significance to our well-being. Disturbed
      communication is by far the most commonly reported effect of hearing loss and
      many handicaps resulting from hearing impairment are of an emotional character.
      Following Goffman and Scheff I argue that fear of losing face is crucial in
      interaction, and that shame is an important emotion. Shame is often hidden,
      misnamed or avoided. But if shame is acknowledged, it is discharged. In
      traditional audiological rehabilitation, the focus is aural perception, visual
      perception and speech. I contend that emotional problems, like shame and
      embarrassment, have to be brought to the fore, the focus less on the compensatory
      side of rehabilitation and more on the acceptance and coping sides.

PMID- 10209788
TI  - Audiology in an ecological perspective--development of a conceptual framework.
AB  - The conceptual framework for describing an audiological communication handicap
      and its underlying processes is built in analogy to a biological, ecological
      system and uses the following primary concepts: interaction, internal milieu,
      preferendum (preferred communication features) and optimal resource utilization.
      From these primary concepts secondary concepts and processes are formulated:
      signal, message/dialogue and behavior are three levels of interaction; adjustment
      and release of mental resources are specifications for preferendum (influenced by
      contextual and social conditions); specificity and facilitation underlie optimal
      resource utilization. The internal environment contains afferent, central and
      efferent speech and language processing, cognitive and emotional processes. The
      main components of audiology and rehabilitation (impairment, disability,
      handicap) are deduced from these concepts and processes. Examples of studies
      based on this conceptual framework are presented briefly. These include an
      environmental test chamber where realistic acoustic environments and
      communication situations can be directly studied, and a rehabilitation programme
      based on tutorial education for structured interaction at the behaviour level
      between hearing-impaired and normal-hearing persons. A vibratory-based event
      localization system for deaf-blind is described which improves specificity and
      thereby mental resource utilization.

PMID- 10209789
TI  - The ligaments and annulus fibrosus of human adult cervical intervertebral discs.
AB  - STUDY DESIGN: Descriptive, microdissection study. OBJECTIVE: To determine the
      morphology of the human adult cervical intervertebral disc and its ligaments.
      SUMMARY OF BACKGROUND DATA: Some studies indicate that the cervical disc is
      distinctly different from the lumbar intervertebral disc, yet most clinical and
      anatomic texts appear content with extrapolating data from the lumbar spine. A
      detailed three-dimensional description of the cervical intervertebral disc and
      its surrounding ligaments is currently unavailable. METHODS: Whole cervical
      spinal columns were freed from 12 human adult embalmed cadavers, and the
      posterior elements and soft tissues were removed. Using microdissection, the
      longitudinal ligaments and the fibrous components of 59 cervical intervertebral
      disc were resected systematically. The orientation, location, and attachments of
      each stripped bundle of collagen were recorded photographically and in sketches.
      RESULTS: The cervical anulus fibrosus does not consist of concentric laminae of
      collagen fibers as in lumbar discs. Instead, it forms a crescentic mass of
      collagen thick anteriorly and tapering laterally toward the uncinate processes.
      It is essentially deficient posterolaterally and is represented posteriorly only
      by a thin layer of paramedian, vertically orientated fibers. The anterior
      longitudinal ligament covers the front of the disc, and the posterior
      longitudinal ligament reinforces the deficient posterior anulus fibrosus with
      longitudinal and alar fibers. CONCLUSIONS: The three-dimensional architecture of
      the cervical anulus fibrosus is more like a crescentic anterior interosseous
      ligament than a ring of fibers surrounding the nucleus pulposus.

PMID- 10209790
TI  - The use of recombinant human bone morphogenetic protein 2 (rhBMP-2) to promote
      spinal fusion in a nonhuman primate anterior interbody fusion model.
AB  - STUDY DESIGN: A study on the efficacy of recombinant human bone morphogenetic
      protein 2 (rhBMP-2) in a nonhuman primate anterior interbody fusion model.
      OBJECTIVES: To investigate the efficacy of rhBMP-2 with an absorbable collagen
      sponge carrier to promote spinal fusion in a nonhuman primate anterior interbody
      fusion model. SUMMARY OF BACKGROUND DATA: RhBMP-2 is an osteoinductive growth
      factor capable of inducing new bone formation in vivo. Although dosage studies
      using rhBMP-2 have been performed on species of lower phylogenetic level, they
      cannot be extrapolated to the primate. Dosage studies on nonhuman primates are
      essential before proceeding with human primate application. METHODS: Six female
      adult Macaca mulatta (rhesus macaque) monkeys underwent an anterior L7-S1
      interbody lumbar fusion. All six sites were assigned randomly to one of two
      fusion methods: 1) autogenous bone graft within a single freeze-dried smooth
      cortical dowel allograft cylinder (control) or 2) rhBMP-2-soaked absorbable
      collagen sponges within a single freeze-dried smooth cortical dowel allograft
      cylinder also soaked in rhBMP-2. The animals underwent a baseline computed
      tomography scan followed by 3- and 6-month postoperation scans. Anteroposterior
      and lateral radiographs of the lumbosacral spine were performed monthly. After
      the monkeys were killed, the lumbar spine fusion sites were evaluated. Histologic
      evaluation of all fusion sites was performed. RESULTS: The three monkeys
      receiving rhBMP-2-soaked collagen sponges with a freeze-dried allograft
      demonstrated radiographic signs of fusion as early as 8 weeks. The control
      animals were slower to reveal new bone formation. The computed tomography scans
      revealed extensive fusion of the L7-S1 lumbar vertebrae in the group with rhBMP
      2. A pseudarthrosis was present in two of the control animals. CONCLUSIONS: This
      study was able to document the efficacy of rhBMP-2 with an absorbable collagen
      sponge carrier and a cortical dowel allograft to promote anterior interbody
      fusion in a nonhuman primate model at a dose of 0.4 mg per implant site (1.5
      mg/mL concentration). The late of new bone formation and fusion with the use of
      rhBMP-2 and cortical dowel allograft appears to be far superior to that of
      autogenous cancellous iliac crest graft with cortical dowel allograft.

PMID- 10209791
TI  - New formulations of demineralized bone matrix as a more effective graft
      alternative in experimental posterolateral lumbar spine arthrodesis.
AB  - STUDY DESIGN: A rabbit model of posterolateral intertransverse process spine
      arthrodesis was used. OBJECTIVE: To determine the efficacy of two new
      formulations of demineralized bone matrix. SUMMARY OF BACKGROUND DATA: The
      flowable gel form of Grafton (Osteotech, Eatontown, NJ) demineralized bone matrix
      has been shown to have osteoinductive properties in various models and currently
      is used clinically as bone graft material in posterolateral lumbar spine
      arthrodesis. Two new formulations of Grafton, one made of flexible sheets (Flex)
      and the other made in a malleable consistency (Putty), have improved handling
      characteristics compared with the gel form. METHODS: In this study, 108 New
      Zealand white rabbits underwent bilateral posterolateral intertransverse spine
      arthrodesis at L5-L6 using autogenous iliac crest bone graft alone (control), one
      of the new forms of demineralized bone matrix (DBM; made from rabbit bone) alone
      or in combination with autogenous iliac crest bone. Rabbits were killed 6 weeks
      after surgery. The lumbar spines were excised, and fusion success or failure was
      determined by manual palpation and radiography. Specimens also were processed for
      undecalcified histologic analysis. RESULTS: Manual palpation of the harvested
      lumbar spines revealed that the fusion rates of the Flex-DBM/Auto group (9/9,
      100%) and Putty-DBM/Auto group (10/10, 100%) were superior (P < 0.01) to those of
      the Auto/control group (3/9, 33%). As a stand-alone graft substitute, Flex-DBM
      performed superiorly with a fusion rate of 11/11 (100%) compared with that of
      Putty-DBM (10/12, 83%) and Gel-DBM (7/12, 58%). The devitalized version of Flex
      DBM had a fusion rate of 4/11 (36%), which was comparable with the devitalized
      Putty-DBM rate of 4/12 (33%). Both were superior (P < 0.05) to the devitalized
      Gel-DBM rate of 0/12 (0%). More mature fusions with greater amounts of trabecular
      bone were present radiographically and histologically in rabbits that received
      all forms of demineralized bone matrix than in those in which autograft was used.
      CONCLUSIONS: The new flexible sheet and malleable putty forms of demineralized
      bone matrix were effective as graft extender and graft enhancer in a model of
      posterolateral lumbar spine fusion. These newer formulations of Grafton appear to
      have a greater capacity to form bone than the gel form or autogenous bone graft
      alone in this model.

PMID- 10209792
TI  - Experimental external fixation combined with percutaneous discectomy in the
      management of scoliosis.
AB  - STUDY DESIGN: An assessment of the value of external fixation with or without
      percutaneous discectomy for the management of scoliosis in young rabbits with
      induced progressive thoracic scoliosis. OBJECTIVES: To investigate in an
      experimental setting the effect of external fixation with or without percutaneous
      discectomy for the management of scoliosis, as a preliminary study to precede
      clinical consideration. SUMMARY OF BACKGROUND DATA: External fixation of the
      spine using percutaneous transpedicular screws has been used clinically for cases
      of traumatic spinal injury, infectious spine, or chronic low back pain caused by
      a disc lesion. Percutaneous discectomy for the management of scoliosis has been
      reported. METHODS: Thirty-two young rabbits underwent partial resection of the
      right lower ribs. Nine rabbits were not treated after production of scoliosis and
      were followed as controls. At 4-6 weeks after production of scoliosis, in 23
      animals, Kirschner wires were inserted percutaneously into the T9-T10 and L1-L2
      disc space, and both ends were attached to an external fixator after correction
      of the scoliosis. In 8 of those 23 animals, percutaneous discectomy was also
      performed at the apex of the caudal compensatory curvature. RESULTS: In these 23
      animals, the initial correction by fixation on of the caudal vertebrae was
      accompanied by a derotation in the apex. Five animals treated with external
      fixation only and four treated with combined percutaneous discectomy survived
      with external fixation until the age of 17 weeks and were followed to the natural
      cessation of the curve progression, at which the fixation was removed and a final
      assessment was made. The mean progression of curvature was 15.8 degrees in the
      group of five animals with external fixation only, and 33.8 degrees in the
      controls. In the group of four animals treated with supplementary percutaneous
      discectomy, however, the treated disc space became rigid, and the mean
      progression of curvature after removal of the fixation was only 5.3 degrees.
      CONCLUSIONS: The results of the current study suggest the potential for external
      fixation to allow for derotation and, when combined with percutaneous discectomy,
      to offer a feasible method of managing scoliosis in the human adolescent. This
      study was a preliminary experimental study; further experimental studies are
      planned to develop this novel technique.

PMID- 10209793
TI  - Pedicle and transverse process screws of the upper thoracic spine. Biomechanical
      comparison of loads to failure.
AB  - STUDY DESIGN: An In vitro biomechanical load-to-failure test. OBJECTIVES: To
      determine the comparative axial pullout strengths of pedicle screw versus
      transverse process screws in the upper thoracic spine (T1-T4), and to compare
      their failure loads with bone density as seen on computed tomography. SUMMARY OF
      THE BACKGROUND DATA: The morphology of the upper thoracic spine presents
      technical challenges for rigid segmental fixation. Though data are available for
      failure characteristics of cervical-lateral mass screws, analogous data are
      wanting in regard to screw fixation of the upper thoracic spine. METHODS: Ten
      fresh-frozen human spines (T1-T4) were quantitatively scanned using computed
      tomography to determine trabecular bone density at each level. The vertebrae were
      drilled and tapped for the insertion of a 3.5-mill meter-diameter cortical bone
      screw in either the pedicle or the transverse process position. A uniaxial load
      to failure was applied. RESULTS: The mean ultimate load to failure for the
      pedicle screws (658 N) was statistically greater than that of the transverse
      process screws (361 N; P < 0.001). The T1 pedicle screw sustained the highest
      load to failure (775 N). No significant difference was found between load to
      failure for the pedicle and transverse process screws at T1. A trend toward
      decreasing load to failure was seen for both screw positions with descending
      thoracic level. Neither pedicle dimensions nor screw working length correlated
      with load to failure. CONCLUSIONS: Upper thoracic pedicle screws have superior
      axial loading characteristics compared with bicortical transverse process screws,
      except at T1. Load behavior of either of these screws was not predictable based
      on anatomic parameters.

PMID- 10209794
TI  - Femoral ring versus fibular strut allografts in anterior lumbar interbody
      arthrodesis. A biomechanical analysis.
AB  - STUDY DESIGN: A comparison between femoral ring and fibular strut allografts in
      anterior lumbar interbody arthrodesis, as assessed by biomechanical analysis.
      OBJECTIVES: To assess the difference in stability and rigidity provided by the
      femoral ring allograft versus that provided by fibular strut allograft. SUMMARY
      OF BACKGROUND DATA: Two commonly used techniques for spinal arthrodesis at L4-L5
      include the femoral ring allograft and the fibular strut allograft. The
      postoperative stability has not been evaluated biomechanically. METHODS: An
      anterior lumbar interbody fusion on seven cadaveric specimens was performed using
      femoral ring and fibular strut allografts. Biplanar radiography was used to
      measure the 6 degrees of motion of L4 with respect to L5 during a range of
      loading maneuvers. RESULTS: When an extension moment was applied, the femoral
      ring allograft extended 4.2 degrees more than the intact specimen, compared with
      1.6 degrees with the fibular strut allograft (P = 0.18). When the flexion moment
      was imposed, lateral bending increased by 2.2 degrees with the femoral ring,
      compared with 0.7 degree with the fibular strut allograft (P = 0.06). During
      lateral bending, increased lateral translation was observed to be 0.9 mm with the
      fibular strut allograft compared with 1.4 mm with the femoral ring allograft (P =
      0.06). CONCLUSIONS: Although not statistically significant, the fibular strut
      allograft creates a more rigid construct immediately after surgery during flexion
      extension, lateral bending angulations, and lateral translation. One should
      consider using the fibular strut allograft over the femoral ring allograft, as it
      is more stable and rigid construct in the immediate postoperative period.

PMID- 10209795
TI  - Geometric measurements of the lumbar spine in Chinese men during trunk flexion.
AB  - STUDY DESIGN: An analysis of the geometric data of the lumbar spine in Chinese
      men. Lateral radiographs were obtained of 16 men in the upright position to a
      trunk flexion of 90 degrees in 30 degrees increments. OBJECTIVES: To establish
      reference data concerning the geometry of the lumbar spine for various degrees of
      trunk flexion. SUMMARY OF BACKGROUND DATA: In previous studies, the morphometry
      and alignment of the lumbar spine have been investigated. Reports of systematic
      analyses of the lumbar spine in trunk flexion have lacked adequate radiographic
      data. Moreover, few studies have focused on measuring lumbar spine geometric data
      in Chinese individuals. METHODS: A total of 67 landmarks on each radiograph were
      identified. They were marked by investigators and digitized using a HyperSpace
      digitizing system (V.17: Mira Imaging Inc., Salt Lake City, UT). The geometric
      configuration of the vertebrae and discs then was derived from the digitized
      points. RESULTS: The dimensions of the vertebrae and disc on the lumbar spine
      obtained in this study were similar to those of previous studies. The motion of
      the lumbosacral spine had the greatest contribution in trunk flexion,
      approximately 90% (i.e., rotating at the rate of 9 degrees for each 10 degrees of
      trunk flexion) when the trunk was flexed from 30 degrees to 60 degrees. After
      that, the hips were dominant in accomplishing the trunk flexion from 60 degrees
      to horizontal. This motion patterns may be useful for making clinical diagnoses
      of lumbar function in Chinese men. CONCLUSIONS: No obvious interracial
      differences were found in the geometric data found in this study, which suggests
      that morphometric data obtained from Caucasian individuals may be applied to
      Chinese patients for clinical purposes.

PMID- 10209796
TI  - Strain on intervertebral discs after anterior cervical decompression and fusion.
AB  - STUDY DESIGN: An analysis of the change in strain distribution of intervertebral
      discs present after anterior cervical decompression and fusion by an original
      method. The analytical results were compared to occurrence of herniation of the
      intervertebral disc on magnetic resonance imaging. OBJECTIVES: To elucidate the
      influence of anterior cervical decompression and fusion on the unfused segments
      of the spine. SUMMARY OF BACKGROUND DATA: There is no consensus regarding the
      exact significance of the biomechanical change in the unfused segment present
      after surgery. METHODS: Ninety-six patients subjected to anterior cervical
      decompression and fusion for herniation of intervertebral discs were examined.
      Shear strain and longitudinal strain of intervertebral discs were analyzed on pre
      and postoperative lateral dynamic routine radiography of the cervical spine.
      Thirty of the 96 patients were examined by magnetic resonance imaging before and
      after surgery, and the relation between alteration in strains and postsurgical
      occurrence of disc herniation was examined. RESULTS: In the cases of double- or
      triple-level fusion, shear strain of adjacent segments had increased 20% on
      average 1 year after surgery. Thirteen intervertebral discs that had an
      abnormally high degree of strain showed an increase in longitudinal strain after
      surgery. Eleven (85%) of the 13 discs that showed an abnormal increase in
      longitudinal strain had herniation in the same intervertebral discs with
      compression of the spinal cord during the follow-up period. Relief of symptoms
      was significantly poor in the patients with recent herniation. CONCLUSIONS: Close
      attention should be paid to long-term biomechanical changes in the unfused
      segment.

PMID- 10209797
TI  - A descriptive study of the centralization phenomenon. A prospective analysis.
AB  - STUDY DESIGN: Occurrence and treatment responses associated with the
      centralization phenomenon were analyzed prospectively in 289 patients with acute
      neck and back pain with or without referred spinal symptoms. OBJECTIVES: To
      document symptom changes to mechanical assessment during initial evaluation and
      during consecutive visits. Using standard operational definitions, patients were
      categorized reliably into three inclusive and mutually exclusive pain pattern
      groups: centralization, noncentralization, and partial reduction. It was
      hypothesized that the occurrence of centralization would be less than previously
      reported and that the centralization group would have better treatment results.
      SUMMARY OF BACKGROUND DATA: Centralization has been reported to occur with high
      frequency during mechanical assessments of patients with acute spinal syndromes.
      When centralization is observed, a favorable treatment result is expected.
      Because centralization has not been defined consistently in the literature, the
      true prevalence and treatment responses associated with centralization have not
      been confirmed. METHODS: Consecutive patients with neck or back pain syndromes
      and referred to outpatient physical therapy services were categorized into three
      pain pattern groups by experienced therapists trained in the McKenzie system.
      Changes in distal pain location were scored and documented before and after each
      visit. Maximal pain intensity over 24 hours, perceived functional status, and
      number of treatment visits were compared between groups. RESULTS: Patients could
      be categorized reliably according to movement signs and symptoms. The
      centralization pain pattern group had significantly fewer visits than the other
      two groups (P < 0.001). Pain intensity rating and perceived function were
      different between the centralization and noncentralization groups (P < 0.001).
      There was no difference in treatment response between the centralization and
      partial-reduction groups (P = 0.306). Prevalence of patients assigned to the
      three groups was 30.8% in the centralization group, 23.2% in noncentralization,
      and 46% in the partial-reduction group. CONCLUSION: Categorization by changes in
      pain location to mechanical assessment and treatment allowed identification of
      patients with improved treatment outcomes and facilitated planning of
      conservative treatment of patients with acute spinal pain syndromes. If a
      proximal change in pain location is not observed by the seventh treatment visit,
      the results of this study support additional medical evaluation for physical or
      nonphysical factors that could be delaying quick resolution of the acute episode.

PMID- 10209798
TI  - Is leg length discrepancy associated with the side of radiating pain in patients
      with a lumbar herniated disc?
AB  - STUDY DESIGN: The association between leg length discrepancy and the side of the
      radiating pain in lumbar disc herniation was investigated in a case series.
      OBJECTIVES: To investigate whether pain tends to radiate into the longer or
      shorter leg in patients with a lumbar herniated disc. SUMMARY OF BACKGROUND DATA:
      No previous studies have investigated the association between leg length
      discrepancy and side of radiating pain in patients with a herniated disc. Results
      of studies of low back pain with radiation and leg length discrepancy are
      inconsistent concerning this association. METHODS: Of 132 consecutive patients
      admitted to a district hospital for surgical management of a lumbar herniated
      disc, leg length discrepancy was assessed using the indirect method as described
      by Calliet. RESULTS: Seventy-three patients (55%) were men, and 59 (45%) were
      women. The mean age was 40 years, and 99% of all herniated discs appeared at L4
      L5 (n = 60) or L5-S1 (n = 71). In 64 (62%) of the 104 patients with a leg length
      discrepancy of 1 mm or more, the pain radiated in the shorter leg (P = 0.02). In
      subgroups of patients with larger leg length discrepancies, similar results were
      found but because of smaller sample sizes, these findings did not each
      statistical significance. In 32 of the 57 men (56.1%), the pain radiated to the
      shorter leg (P = 0.43); this was observed in 33 of the 47 women (70.2%; P =
      0.01). CONCLUSION: The results of this study showed a statistically significant
      association between leg length discrepancy and the side of radiating pain in a
      case series of patients with lumbar herniated discs. The relation was more
      pronounced and statistically significant in women only.

PMID- 10209799
TI  - Stability of lumbar fusion with transpedicular fixation determined by roentgen
      stereophotogrammetric analysis.
AB  - STUDY DESIGN: An evaluation of the intervertebral stability of transpedicular
      instrumentation in posterolateral lumbar fusions by roentgen
      stereophotogrammetric analysis. OBJECTIVES: To determine the in vivo
      intervertebral stability of posterolateral lumbar fusions augmented with
      transpedicular screws and plates. SUMMARY OF BACKGROUND DATA: Transpedicular bone
      screw systems have been found to be as safe and clinically effective as other
      types of devices in stabilizing surgery of the spine. Many experimental studies
      have yielded basic data on the stabilizing implant effect in vitro, but the exact
      in vivo stabilizing effect on human lumbar vertebrae has not been presented
      previously. METHODS: In 12 patients, the intervertebral stability of
      posterolateral fusion in the lower lumbar spine augmented with transpedicular
      screws and plates was evaluated by serial roentgen stereophotogrammetric analysis
      with the patients in supine and erect positions 1 year after surgery. RESULTS:
      Screws in each fused vertebra yielded stable fixation or permitted sagittal
      intervertebral translations smaller than 1 mm induced by the positional change. A
      widely decompressed and destabilized vertebra without screw fixation yielded
      persisting intervertebral translations. CONCLUSIONS: The current study
      demonstrated the adequacy of in vivo stability of lumbar fusions augmented with
      transpedicular screws and plates. Sagittal translation seems easier to elicit
      than movements along the other three-dimensional axes. A widely decompressed and
      destabilized vertebra without screw fixation increases the risk for persisting
      intervertebral translations. The roentgen stereophotogrammetric analysis
      technique described seems to be a good way of comparing the in vivo behavior of
      different implant systems.

PMID- 10209800
TI  - Is occupational low back pain on the rise?
AB  - STUDY DESIGN: A retrospective analysis of back pain claim data from two sources,
      a workers' compensation provider and Washington State Department of Labor and
      Industries. The Workers' Compensation Provider claim data were examined over a 9
      year period, 1987-1995, and the Washington claim data were examined over a 5-year
      period, 1991-1995. In addition, a third source of data, reports of back pain from
      the the Bureau of Labor Statistics, was examined over a 4-year period, 1992-1995.
      OBJECTIVES: To characterize occupational low back pain trends in the United
      States. More specifically, trends in back pain rates and costs as well as back
      injury rates from the Bureau of Labor Statistics were discerned. SUMMARY OF
      BACKGROUND DATA: The literature often refers to a recent rise in occupational low
      back pain. However, the question is: Do empirical data support this notion?
      METHODS: Retrospective analysis of workers' compensation provider, Washington
      State, and Bureau of Labor Statistics data. RESULTS: The U.S. estimate of the
      annual low back pain claim rate decreased 34% between 1987 and 1995, although the
      trend was not monotonic. There was a sharper decrease in the U.S. estimate of the
      annual low back pain claim costs during this time (58%). In 1995, however,
      occupational low back pain remained a major problem in the U.S.: an estimated
      $8.8 billion was spent on low back pain claims, and the rate of filing low back
      pain claims was 1.8 per 100 workers. CONCLUSIONS: Evidence of a rise in
      occupational low back pain was not discerned for the 8-year period studied. Data
      from three sources support this finding. However, occupational back pain remains
      a major problem in the U.S.

PMID- 10209801
TI  - Dynamic forces acting on the lumbar spine during manual handling. Can they be
      estimated using electromyographic techniques alone?
AB  - STUDY DESIGN: Compressive loading of the lumbar spine was analyzed using
      electromyographic, movement analysis, and force-plate techniques. OBJECTIVES: To
      evaluate the inertial forces that cannot be detected by electromyographic
      techniques alone. SUMMARY OF BACKGROUND DATA: Links between back pain and manual
      labor have stimulated attempts to measure spine compressive loading. However,
      direct measurements of intradiscal pressure are too invasive, and force plates
      too cumbersome for use in the workplace. Electromyographic techniques are
      noninvasive and portable, but ignore certain inertial forces. METHODS: Eight men
      lifted boxes weighing 6.7 and 15.7 kg from the ground, while joint moments acting
      about L5-S1 were quantified 1) by using a linked-segment model to analyze data
      from Kistler force plates and a Vicon movement-analysis system, and 2) by
      measuring the electromyographic activity of the erector spinae muscles,
      correcting it for contraction speed and comparing it to moment generation during
      static contractions. The linked-segment model was used to calculate the "axial
      thrust," defined as the component of the L5-S1 reaction force that acts along the
      axis of the spine and that is unrelated to trunk muscle activity or static body
      weight. RESULTS: Peak extensor moments predicted by the two techniques were
      similar and equivalent to spinal compressive forces of 2.9-4.8 kN. The axial
      thrust "hidden" from the electromyographic technique was negligible during slow
      lifts, and remained below 4% of peak spinal compression even during fast heavy
      lifts. Peak axial thrust was proportional to the peak vertical ground reaction
      (R2 = 0.74). CONCLUSIONS: Electromyographic techniques can measure dynamic spinal
      loading, but additional force-plate data would improve accuracy slightly during
      lifts requiring a vigorous upward thrust from the legs.

PMID- 10209802
TI  - Influence of estrogen-progestin treatment on back pain and disability among slim
      premenopausal women with low lumbar spine bone mineral density. A 2-year placebo
      controlled randomized trial.
AB  - STUDY DESIGN: A 2-year randomized controlled trial. OBJECTIVES: To examine the
      possible preventive or aggravating effect of estrogen-progestin treatment on the
      back symptoms of slim premenopausal women with low lumbar spine bone mineral
      density. SUMMARY OF BACKGROUND DATA: The incidence of back pain, sciatica, or
      both starts to increase clearly among 45-54-year-old Finnish women. METHODS:
      Forty-eight 39- to 49-year-old premenopausal women with a body mass index of 21
      or less and a lumbar spine bone mineral density (L2-L4) of 1.1 +/- 1 g/cm3 or
      less compared with the normative population were recruited into the study. The
      women were assigned randomly to receive either estradiol-noretisteron acetate
      treatment or placebo. Back pain, symptoms, and disability were assessed with the
      Million and Oswestry questionnaires and pain drawings during the follow-up period
      at 0, 12, and 24 months. Inquiry also was made concerning previous back pain and
      sciatica history. RESULTS: There was a statistically significant decrease in
      nighttime back pain (P < 0.001) and the total Oswestry disability scores (P <
      0.004) in the hormone-treated group compared with the control group during the
      follow-up, but no statistically significant differences were found in daytime
      back pain. At baseline, the cumulative incidence in a history of pain radiating
      from the buttock to the foot in this osteopenic study group was 31/48, (64.5%;
      95% CI 50.5-78.6), which is much more than the predicted 20/48, (42.4%; 95% CI
      39.0-45.7) at this age according to a previous population study. The cumulative
      incidence of at least one back pain episode 44/48, (91.7%; 95% CI 83.6-99.8) was
      somewhat higher in these participants than was predicted for a comparative
      population of women this age, 38/48 (79.2%; 95% CI 70.2-87.3). CONCLUSIONS: It
      seems that this regimen may have alleviating effects on nighttime back pain and
      functional back disability in slim osteopenic premenopausal women.

PMID- 10209803
TI  - One-stage decompression and posterolateral and interbody fusion for severe
      spondylolisthesis. An analysis of 14 patients.
AB  - STUDY DESIGN: A retrospective study of 14 patients with high-grade L5-S1
      spondylolisthesis surgically treated with one-stage decompression and
      posterolateral and interbody fusion (technique of Bohlman and Cook). OBJECTIVE:
      To determine the efficacy of this technique in managing severe lumbosacral
      spondylolisthesis. SUMMARY OF BACKGROUND DATA: Controversy exists over the most
      appropriate method for managing high-grade spondylolisthesis. Circumferential in
      situ fusion from a single-stage posterior approach was described in 1982, but to
      the current authors' knowledge, there are not many reports on clinical results in
      the literature. The current authors studied 14 patients (mean age, 21 years) with
      severe L5-S1 spondylolisthesis. The percentage of slipping averaged 77%; slip
      angle averaged 36 degrees. The average follow-up period was 30 months. All
      patients had severe back or radicular symptoms. Two patients had foot drop, and
      four had minor neurologic dysfunction. Four patients had extremely tight
      hamstrings. METHODS: Pre- and postoperative radiographic films and computed
      tomography scans were reviewed. Magnetic resonance imaging was carried out in 11
      patients before surgery and at follow-up examination. Patients were evaluated for
      fusion rate, clinical outcome, and complications. RESULTS: All six patients with
      motor deficit of the nerve roots showed complete strength recovery at follow-up
      examination. None of the patients had tightness of hamstrings. Twelve patients
      demonstrated incorporation of the graft with solid fusion, one patient had a
      fracture of the fibular graft, and one had graft resorption. All patients but one
      rated the surgical result as excellent. One patient was not satisfied with the
      cosmetic result. Transient paresthesias in the leg of the donor graft were
      documented in two patients. CONCLUSIONS: Posterior decompression of the spinal
      canal combined with anterior and posterior arthrodesis performed at one stage
      through a posterior approach is a safe and effective technique for managing
      severe spondylolisthesis.

PMID- 10209804
TI  - Diagnosis of Os odontoideum using kinematic magnetic resonance imaging. A case
      report.
AB  - STUDY DESIGN: A case of os odontoideum diagnosed using kinematic magnetic
      resonance imaging is presented. OBJECTIVES: To evaluate the kinematic magnetic
      resonance imaging findings of os odontoideum and the possible use these findings
      might have to guide treatment. BACKGROUND: Kinematic magnetic resonance imaging
      is a new imaging modality that is able to produce realtime images of a structure
      through a range of motion. This makes it well suited for investigating dynamic
      processes such as cervical instability. METHODS: A single subject with known os
      odontoideum was examined using a Sigma SPR Kinematic Magnetic Resonance Imager
      (General Electric, Florence, SC). RESULTS: Kinematic magnetic resonance imaging
      demonstrated cervical spinal cord impingement and cervical instability throughout
      flexion and extension, but not during lateral bending or rotation. CONCLUSIONS:
      Kinematic magnetic resonance imaging can evaluate the cervical spine in an
      axially loaded position throughout its range of motion. This modality may be a
      useful method for diagnosing and classifying abnormalities of the spine.

PMID- 10209805
TI  - The importance of an intact abdominal musculature mechanism in maintaining spinal
      sagittal balance. Case illustration in prune-belly syndrome.
AB  - STUDY DESIGN: A rare case of thoracic hypokyphotic deformity secondary to prune
      belly syndrome is presented. OBJECTIVES: To discuss the role of an intact
      abdominal musculature mechanism in maintaining spinal sagittal balance, and to
      present a case illustration of prune-belly syndrome. SUMMARY OF BACKGROUND DATA:
      There has been an ongoing debate concerning the integrity of the abdominal
      musculature unit in maintaining spinal support and stability. It is now believed
      that intra-abdominal pressure hitherto generated plays an important role in the
      stabilization of the spine. Congenital aplasia of the abdominal musculature,
      termed prune-belly syndrome, might therefore result in the loss of spinal
      function and stability. The literature also is reviewed for the incidence of
      spinal deformities related to this condition. METHODS: A unique case of prune
      belly syndrome in a 33-year-old man with congenital aplasia of the abdominal
      musculature is presented. RESULTS: The patient exhibited loss of the spinal
      sagittal balance, with resultant development of a thoracic hypokyphotic deformity
      and thoracolumbar scoliosis. CONCLUSIONS: Scoliosis appears to be the most
      commonly reported spinal deformity. Unequal compressive forces on the vertebral
      endplates may be the proposed mechanism for the spinal deformities. Compensatory
      lumbar paraspinal overactivity resulting from the inability to generate normal
      intra-abdominal pressures because of a deficient abdominal wall musculature
      mechanism seems to be the plausible explanation for the observed thoracic
      hypokyphatic deformity.

PMID- 10209806
TI  - Molecular biology and spinal disorders. A survey for the clinician.
AB  - Over the past 10 years, advances in molecular biology techniques have extended
      the potential for understanding spinal disorders from the microscopic
      (histologic) level down to the molecular level of gene expression within
      individual cells. These advances are initiating new avenues of research and,
      ultimately, novel clinical treatments. The intent of this update is to provide
      the spine clinician with a basic understanding of molecular biology, the type of
      information that may be learned from its application, and the potential for gene
      therapy in spine disorders.

PMID- 10209807
TI  - "The pathomechanism of isthmic lumbar spondylolisthesis: a biomechanical study in
      immature calf spines".

PMID- 10209808
TI  - Geographically masking health data to preserve confidentiality.
AB  - The conventional approach to preserving the confidentiality of health records
      aggregates all records within a geographical area that has a population large
      enough to ensure prevention of disclosure. Though this approach normally protects
      the privacy of individuals, the use of such aggregated data limits the types of
      research one can conduct and makes it impossible to address many important health
      problems. In this paper we discuss the design and implementation of geographical
      masks that not only preserve the security of individual health records, but also
      support the investigation of questions that can be answered only with some
      knowledge about the location of health events. We describe several alternative
      methods of masking individual-level data, evaluate their performance, and discuss
      both the degree to which we can analyse masked data validly as well as the
      relative security of each approach, should anyone attempt to recover the identity
      of an individual from the masked data. We conclude that the geographical masks we
      describe, when appropriately used, protect the confidentiality of health records
      while permitting many important geographically-based analyses, but that further
      research is needed to determine how the power of tests for clustering or the
      strength of other associative relationships are adversely affected by the
      characteristics of different masks.

PMID- 10209809
TI  - Estimating AIDS incidence and jack-knife variance from a continuous delay
      distribution and incomplete data.
AB  - Usual methods for estimating AIDS incidences are based on the inflation of a
      discrete reporting delay distribution, which often results in very imprecise
      estimates of the incidence in the most recent past. In this paper, we propose an
      alternative approach to estimate the AIDS incidence by inflating a continuous
      reporting delay distribution for each reported case. Covariate effects on
      reporting delays are evaluated by a proportional hazards model for the reverse
      time hazard function. A jack-knife variance for the estimated AIDS incidence is
      given. Study results showed that precision of estimates is improved by using the
      continuous time model as compared with those estimates given by its discrete
      counterpart. This feature is useful in assessing current trends in AIDS
      incidence.

PMID- 10209810
TI  - Explaining community-level variance in group randomized trials.
AB  - Between-community variance or community-by-time variance is one of the key
      factors driving the cost of conducting group randomized trials, which are often
      very expensive. We investigated empirically whether between-community variance
      could be reduced by controlling individual- and/or community-level covariates and
      identified these covariates from four large community-based group randomized
      trials or surveys: the Working Well Trial; Kaiser Adolescent Survey; Kaiser
      Adults Survey; and the Eating Patterns Study. We found that adjusting for
      covariates will often substantially reduce the between-community variance
      component. Therefore investigators could block the communities according to these
      covariates, or adjust for these covariates to improve the power of community
      trials. We found that the community-by-time variance components are always near
      zero in these data sets, especially for the surveys where a cohort was followed
      over time. The covariate adjustment had less impact on reducing the community-by
      time variance for the cohort samples than for the cross-sectional samples. This
      suggests that blocking may not be necessary for the design of the group
      randomized trials where the change from baseline is of primary interest. The
      Working Well Trial data were used to illustrate this point.

PMID- 10209811
TI  - Methods for combining rates from several studies.
AB  - When several independent groups have conducted studies to estimate a procedure's
      success rate, it is often of interest to combine the results of these studies in
      the hopes of obtaining a better estimate for the true unknown success rate of the
      procedure. In this paper we present two hierarchical methods for estimating the
      overall rate of success. Both methods take into account the within-study and
      between-study variation and assume in the first stage that the number of
      successes within each study follows a binomial distribution given each study's
      own success rate. They differ, however, in their second stage assumptions. The
      first method assumes in the second stage that the rates of success from
      individual studies form a random sample having a constant expected value and
      variance. Generalized estimating equations (GEE) are then used to estimate the
      overall rate of success and its variance. The second method assumes in the second
      stage that the success rates from different studies follow a beta distribution.
      Both methods use the maximum likelihood approach to derive an estimate for the
      overall success rate and to construct the corresponding confidence intervals. We
      also present a two-stage bootstrap approach to estimating a confidence interval
      for the success rate when the number of studies is small. We then perform a
      simulation study to compare the two methods. Finally, we illustrate these two
      methods and obtain bootstrap confidence intervals in a medical example analysing
      the effectiveness of hyperdynamic therapy for cerebral vasospasm.

PMID- 10209812
TI  - Estimation of the average correlation coefficient for stratified bivariate data.
AB  - If the relationship between two ordered categorical variables X and Y is
      influenced by a third categorical variable with K levels, the Cochran-Mantel
      Haenszel (CMH) correlation statistic QC is a useful stratum-adjusted summary
      statistic for testing the null hypothesis of no association between X and Y.
      Although motivated by and developed for the case of K I x J contingency tables,
      the correlation statistic QC is also applicable when X and Y are continuous
      variables. In this paper we derive a corresponding estimator of the average
      correlation coefficient for K I x J tables. We also study two estimates of the
      variance of the average correlation coefficient. The first is a restricted
      variance based on the variances of the observed cell frequencies under the null
      hypothesis of no association. The second is an unrestricted variance based on an
      asymptotic variance derived by Brown and Benedetti. The estimator of the average
      correlation coefficient works well in tables with balanced and unbalanced
      margins, for equal and unequal stratum-specific sample sizes, when correlation
      coefficients are constant over strata, and when correlation coefficients vary
      across strata. When the correlation coefficients are zero, close to zero, or the
      cell frequencies are small, the confidence intervals based on the restricted
      variance are preferred. For larger correlations and larger cell frequencies, the
      unrestricted confidence intervals give superior performance. We also apply the
      CMH statistic and proposed estimators to continuous non-normal data sampled from
      bivariate gamma distributions. We compare our methods to statistics for data
      sampled from normal distributions. The size and power of the CMH and normal
      theory statistics are comparable. When the stratum-specific sample sizes are
      small and the distributions are skewed, the proposed estimator is superior to the
      normal theory estimator. When the correlation coefficient is zero or close to
      zero, the restricted confidence intervals provide the best performance. None of
      the confidence intervals studied provides acceptable performances across all
      correlation coefficients, sample sizes and non-normal distributions.

PMID- 10209813
TI  - Bootstrap approach for constructing confidence intervals for population
      pharmacokinetic parameters. I: A use of bootstrap standard error.
AB  - In population pharmacokinetic studies, one of the main objectives is to estimate
      population pharmacokinetic parameters specifying the population distributions of
      pharmacokinetic parameters. Confidence intervals for population pharmacokinetic
      parameters are generally estimated by assuming the asymptotic normality, which is
      a large-sample property, that is, a property which holds for the cases where
      sample sizes are large enough. In actual clinical trials, however, sample sizes
      are limited and not so large in general. Likelihood functions in population
      pharmacokinetic modelling include a multiple integral and are quite complicated.
      We hence suspect that the sample sizes of actual trials are often not large
      enough for assuming the asymptotic normality and that the asymptotic confidence
      intervals underestimate the uncertainties of the estimates of population
      pharmacokinetic parameters. As an alternative to the asymptotic normality
      approach, we can employ a bootstrap approach. This paper proposes a bootstrap
      standard error approach for constructing confidence intervals for population
      pharmacokinetic parameters. Comparisons between the asymptotic and bootstrap
      confidence intervals are made through applications to a simulated data set and an
      actual phase I trial.

PMID- 10209814
TI  - Bootstrap approach for constructing confidence intervals for population
      pharmacokinetic parameters. II: A bootstrap modification of standard two-stage
      (STS) method for phase I trial.
AB  - For population pharmacokinetics in phase I trials, the standard two-stage (STS)
      method is quite appealing, especially to non-statisticians, because the method is
      theoretically and computationally simple. The method, however, does not take into
      account the uncertainty in estimating individual-specific parameters and gives
      biased estimates for population variances of pharmacokinetic parameters. This is
      one of the main reasons why the STS method is not generally recommended. This
      paper proposes a simple bootstrap modification of the STS method for estimating
      confidence intervals of population means and standard deviations of
      pharmacokinetic parameters in phase I trials. The proposed approach adopts a
      bootstrap bias correction in estimating population variances of pharmacokinetic
      parameters. Applications are given to a simulated data set and an actual phase I
      trial to show how the proposed approach works in practice.

PMID- 10209815
TI  - Exact simultaneous confidence bands for a collection of univariate polynomials in
      regression analysis.
AB  - We discuss a simple simulation method for construction of exact confidence bands,
      having a pre-assigned confidence level simultaneously for several regression
      functions which are univariate polynomials in the predictors. This is
      accomplished by combining and extending existing results in a manner that permits
      both finite and infinite ranges for individual predictor variables. We illustrate
      the method for a logistic regression model with both dichotomous and continuous
      predictors.

PMID- 10209816
TI  - Histopathological and electron microscopical observations on rainbow trout fry
      syndrome.
AB  - Rainbow trout (Oncorhynchus mykiss) fry and fingerlings with clinical signs of
      rainbow trout fry syndrome, and rainbow trout (0.5 to 3.5 g) with experimentally
      induced infections with Flavobacterium psychrophilum, were examined
      histopathologically and electron microscopically. Severe hypertrophy of the
      spleen and cellular degeneration were consistently observed. Distinctive features
      of the disease were the loss of definition of the splenic border and its
      replacement by a loosely structured eosinophilic layer, fibrinous inflammation
      and intercellular oedema within the spleen, and the presence of numerous
      filamentous bacteria interspersed throughout the organ.

PMID- 10209817
TI  - Equine glanders in Turkey.
AB  - In the course of an epidemiological study of glanders on a number of Turkish
      islands in the Sea of Marmara, 1128 horses were examined by using the
      intracutaneous mallein test. Thirty-five (3-1 per cent) developed an increase in
      rectal temperature and a swelling at the point of injection. Ten of these horses
      were killed and glanders was confirmed in five cases by the presence of lesions
      and by the immunohistological demonstration of the causative agent, Burkholderia
      mallei. Clinical and pathological findings indicated that in all cases the
      infection was restricted to the mucous membrane of the nasal cavity with its
      parasinus, the nostrils and the upper lips. It was confirmed that equine glanders
      is endemic in Turkey.

PMID- 10209818
TI  - Use of phenytoin to treat digitalis-induced cardiac arrhythmias in a miniature
      Shetland pony.
AB  - Two miniature Shetland ponies showing clinical signs of Digitalis purpurea
      (foxglove) poisoning were examined. One animal died shortly afterwards, but the
      second was treated successfully with the anti-arrhythmic agent, phenytoin, and
      was discharged after 16 days.

PMID- 10209819
TI  - Diagnosis of canine leishmaniasis by a polymerase chain reaction technique.
AB  - A polymerase chain reaction (PCR) technique for the diagnosis of canine
      leishmaniasis on bone marrow samples was developed which amplified a 120 bp DNA
      fragment of the Leishmania kinetoplast DNA, common to all Leishmania species.
      Forty-five of 46 dogs in which leishmaniasis had been diagnosed were positive
      with the PCR technique, whereas none of 41 healthy dogs gave a positive result.
      Fifteen dogs with leishmaniasis that had been treated for six months with N
      methylglucamine antimoniate and allopurinol were also investigated. Seven were
      positive, implying that they remained infected despite the resolution of their
      clinical signs.

PMID- 10209820
TI  - Progressive hindlimb paraparesis in a goat associated with a vascular hamartoma.

PMID- 10209821
TI  - Effect of epidermal growth factor on the cumulus expansion, meiotic maturation
      and development of buffalo oocytes in vitro.

PMID- 10209822
TI  - Type 1 diabetes mellitus in a pregnant heifer persistently infected with bovine
      viral diarrhoea virus.

PMID- 10209823
TI  - Neutering pet rabbits.

PMID- 10209824
TI  - Neutering pet rabbits.

PMID- 10209825
TI  - Continuing ban on beef on the bone.

PMID- 10209826
TI  - Chewing lice, sheep scab and systemic endectocides.

PMID- 10209827
TI  - Piglet tail necrosis.

PMID- 10209828
TI  - [Primary and secondary prevention of coronary heart disease: what can we
      afford?].
AB  - In secondary prevention, statins are cost-effective and even more cost-effective
      than other lipd lowering drugs. Statins are especially favorable in patients with
      previous myocardial infarction compared to those with angina pectoris. For
      secondary prevention of coronary heart disease, statins should be administered
      generously. In primary prevention, statins are effective but not cost-efficient.
      Unfavorable results have to be expected especially in premenopausal women,
      younger patients, and in those with a low risk factor profile. For population
      based primary prevention, only dietary measures can be advocated; however, apart
      from a serious lack of compliance their efficiency has not yet been proven.
      Preventive measures have their own prize; in general they are considered not to
      prevent coronary heart disease but retard it. Therefore, such therapeutic
      interventions can be assumed not to reduce but rather to increase the "direct"
      medical costs. Furthermore, successful prevention of coronary heart disease
      leads, due to life-prolongation, to an increase in people out of work and in
      disabled patients due to age and/or disease. Therefore, an increase especially of
      the "indirect" costs for unemployment, pension, nursing homes, etc. must be
      expected.

PMID- 10209829
TI  - [The current situation in training and education of assistant staff in
      interventional cardiology].
AB  - The number of heart catheter laboratories in Germany has been increasing for
      years. While there are general training regulations for cardiologists, nothing
      comparable exists for the assistant staff in interventional cardiology.
      Qualification is settled within the department. Aim of this study was the
      determination of the demand in general training and qualification courses. All
      heart catheter laboratories in North Rhine-Westphalia were questioned. Assistants
      (227) and medical directors (43) from 48 laboratories (54.0% returns) answered.
      Of the assistants 59.1% were qualified nurses, 28.2% consulting room assistants,
      and 10.1% medical technicians. Most of them were female (85.0%); the average age
      was 34.3 years. Of the assistants 73.1% were not trained in their current
      hospital or practice. Before their occupation in cardiac catheterization, 51.8%
      worked in nursing and 17.6% in ECG, sonography, etc. None of the 227 assistants
      was still in training at the time of questioning although 68.3% of the hospitals
      and practices accept trainees. Nine out of ten laboratories offer inhouse
      qualification, mainly in radiation protection (82.1%) and medical fields (66.7%),
      and 85.3% of the assistants have already attended these. Of the medical directors
      90.0% and 99.2% of the assistants consider general training and qualification
      courses to be necessary. When asked for important fields for training programs,
      the assistant staff mentions "medicine" (77.6%), "examination assistance"
      (67.0%), and "EDP" (60.4%), while the medical directors place importance on
      "quality management" (89.2%) and "radiation protection" (86.5%). The job market
      for assistants the interventional cardiology is still good: 14.3% of the
      laboratories plan to take on new employees, 61.9% want to keep their number of
      assistants. The share of part-time work is low (16.8%). The momentary
      qualification and training of assistant staff in interventional cardiology does
      not match the demand. General programs for trainees with universally applicable
      teaching objectives and examination regulations are necessary.

PMID- 10209830
TI  - [Transesophageal electroconversion of atrial reentrant tachycardias early or late
      following surgery for congenital heart disease].
AB  - Atrial reentrant tachycardias (ART) are a potentially life-threatening
      complication in survivors of congenital heart disease surgery. From July 1993 to
      December 1997, temporary transesophageal pacing was used to convert 29
      tachycardia episodes in 19 patients. At the time of the first tachycardia
      episode, patients' ages were 1 month to 26 years (mean 9.8 yrs). Time from
      operation to onset of first tachycardia episode ranged from 1 day to 19 years.
      Onset was within the first 2 weeks postoperatively in 6 patients and occurred
      later in 13 patients (1 to 19 years after operation). Postoperative pacemaker
      implantation had been performed in 2 pts; 17 of 19 pts were receiving
      antiarrhythmic medication. After placing a quadripolar transesophageal catheter,
      atrial and ventricular signals were recorded and atrial stimulation performed.
      Atrial cycle length of tachycardia ranged from 160-380 ms with 1:1 to 4:1 AV
      conduction. Temporary transesophageal pacing was performed following an algorithm
      starting with 4 extrastimuli (20 ms below atrial cycle length of tachycardia).
      Tachycardia terminated in 27 of 29 cases (93%) without complications. In 3 cases,
      conversion was achieved by pacing after amiodarone 5 mg/kg i.v. After tachycardia
      conversion, sinus- or pacemaker rhythm was present in 20 cases. In 9 cases atrial
      fibrillation was recorded; spontaneous conversion to sinus rhythm occurred after
      a maximum of 3 min (7 cases) or persisted and required direct current
      cardioversion (2 cases). In conclusion, transesophageal atrial pacing is an
      effective, relatively noninvasive method for conversion of atrial reentrant
      tachycardias after operation for congenital heart disease.

PMID- 10209831
TI  - [Is ICD-programming for double intraoperative defibrillation threshold energy
      safe and effective during long-time follow-up? Results of a prospective
      randomized multicenter study (Low-Energy Endotak Trial--LEET)].
AB  - The aim of this prospective and randomized study was to evaluate the safety and
      efficacy of a reduced shock strength in transvenous implantable defibrillator
      therapy. So far clinical data concerning the safety margin of the shock energy in
      ICD therapy do not exist. The shock energy tested during long-term follow-up in
      this study was twice the intraoperatively measured defibrillation threshold
      (DFT). A total number of 176 consecutive patients representing a typical cohort
      of ICD patients were evaluated. All patients received a non-thoracotomy lead
      system (CPI, Endotak 0070, 0090) and a biphasic cardioverter-defibrillator with
      the ability to store episodes (Cardiac Pacemakers Inc., Ventac TM PRx II, PRx
      III). The intraoperative defibrillation threshold (DFT) was evaluated in a step
      down protocol (15, 10, 8, 5 J) and had to be < or = 15 J for inclusion into the
      study. The lowest effective energy terminating induced ventricular fibrillation
      had to be confirmed and was defined as DFT+ augmented defibrillation threshold.
      The DFT+ value was tested immediately after successful implantation, at
      discharge, and after a follow-up period of one year. Prior to implantation the
      patients were randomized into two groups. The energy of the first shock in the
      study group was programmed at twice DFT+ and in the control group at the maximum
      energy output (34 J). The efficacy of the first shock and its reproducibility in
      DFT testings and in spontaneous episodes during long-term follow-up of the study
      group were compared to those in the control group. A DFT+ value was found to be <
      or = 15 J in 166 of 176 patients (94%). The DFT+ in the study group was 9.6 +/-
      3.2; in control group 10.1 +/- 3.5 J. The prohability of successful
      defibrillation at DFT+ level after one year was 84%. The success rate of the
      first shock meant to terminate induced ventricular fibrillation (VF) was 99.5% in
      the study group (217 of 218 episodes) and 99% in the control group (201 of 203
      episodes). During follow-up of 24 +/- 9 months spontaneous episodes in the study
      group, 83/86 (96.5%) monomorphic ventricular tachycardias (MVT) and 38/40 (95%)
      VF-episodes were converted successfully by the 2x DFT+ shock. In the control
      group the first shock was successful in 151/156 (96.8%) spontaneous MVTs and in
      30/33 (91%) VF episodes. The efficacy of the first shock was not influenced by
      clinical data such as the underlying cardiac disease, left ventricular function,
      ongoing antiarrhythmic therapy with amiodarone, or the number of spontaneous
      episodes per day or by the DFT itself. At a mean follow-up of two years there was
      no significant difference between the two groups concerning the incidence of
      sudden cardiac death (2.4% in the study group vs. 3.8% in the control group). In
      conclusion programming the first shock with the ICD lead system used in this
      study at 2x DFT+ is as efficient as a shock energy of 34 J in order to terminate
      induced and spontaneous episodes of VT/VF. Thus, the safety of ICD-therapy is not
      impaired when programming the shock energy at the 2x DFT+ value.

PMID- 10209832
TI  - [Improvement of physical performance and aerobic capacity mediated by a novel 4-
      week ambulatory cardiac rehabilitation program].
AB  - During a 4-week ambulatory cardiac rehabilitation program, 262 patients with
      coronary artery disease (CAD), 235 men and 27 women, 53.6 +/- 10.2 years,
      performed 30.5 +/- 2.9 exercise units. Before and after the rehabilitation
      program exercise, capacity was assessed by bicycle ergometry. There was a
      significant (p < 0.001) increase in the maximum exercise capacity at the end of
      the program (105.3 +/- 32.3 vs. 121.9 +/- 37.3 W). Physical work capacity on the
      2.0 mmol lactate level improved (p < 0.001) from 72.2 +/- 23.5 to 86.4 +/- 25.8
      W, on the 2.5 mmol/l level (p < 0.001) from 83.5 +/- 23.2 to 97.4 +/- 26.4 W, and
      on the 3.0 mmol/l level (p < 0.001) from 93.1 +/- 23.0 to 106.6 +/- 26.1 W.
      Despite enhanced performance, heart rate remained unaltered on the 2.0, 2.5, and
      3.0 mmol/l lactate level. Furthermore, ergometric performance on predefined heart
      rate levels was significantly (p < 0.001) increased: 85/min: from 56.0 +/- 24.1
      to 65.8 +/- 24.5 W, 90/min: from 62.0 +/- 27.3 to 71.2 +/- 26 W; 95/min: from
      67.2 +/- 26.4 to 77.5 +/- 27.6 W; 100/min: from 71.1 +/- 29.6 to 80.6 +/- 28.1 W;
      105/min: from 69.8 +/- 26.2 to 81.9 +/- 28.2 W and 110/min: from 73.6 +/- 28.9 to
      90.4 +/- 29.4 W. The results demonstrate that physical performance in patients
      with CAD was improved by our novel ambulatory cardiac rehabilitation program.
      This improvement included an increase in maximum as well as endurance work
      capacity; furthermore, this increase was accompanied by a decrease in resting and
      exercise heart rates. The results demonstrate an absolute increase of physical
      performance, more importantly an increase of physical performance at defined
      lactate levels in the presence of unchanged heart rates mediated by the
      rehabilitation program. Thus, this increase was independent of motivational
      factors in the patients and/or the investigators during the re-exercise test. On
      the contrary, our data demonstrate that it is based on an improvement of aerobic
      endurance capacity associated with a therapeutically beneficial significant
      decrease of heart rate for a defined workload. The effects were independent of
      pharmacological influences (e.g., beta-receptor antagonists). These findings are
      of clinical importance with respect to reduction of myocardial oxygen consumption
      in patients with CAD.

PMID- 10209833
TI  - [Direct coronary stent implantation without predilatation--a new therapeutic
      approach with a special balloon catheter design].
AB  - Stent implantation serves as the gold standard for proximal lesions of the
      coronary arteries with a diameter between 2.75-3.5 mm. Our new concept aims at a
      reduced procedure duration and fluoro-time as well as a decreased ischemic period
      during stent implantation. A new therapeutic concept of a direct stent
      implantation without predilatation was tested using a specially developed balloon
      catheter on which various 14-16 mm long "slotted-tube" stents are mounted between
      two conical, radiopaque markers. In 105 consecutive patients, who were scheduled
      for angioplasty, this method of direct stent implantation was performed. Six of
      the procedures were performed for acute myocardial infarction and 8 in so-called
      high-risk procedures. The direct stent implantation was successful in 88%. In 6%,
      predilatation of the lesion site was necessary before stent placement. In the
      remaining 6%, a stent could not be successfully implanted despite the
      availability of various other systems. Comparison of the direct stent
      implantation with conventional stent placement with predilatation revealed that
      1) The fluoro-time for direct stent implantation, compared to the conventional
      method, was 8.4 +/- 4.9 min vs. 13.7 +/- 8.0 min; p < 0.05, respectively.
      Furthermore, there were less balloons used per lesion for direct stent
      implantation (1.4 +/- 0.4) compared to the conventional method (1.7 +/- 0.7), but
      there was not a significant difference. 2) If we compare those patients with
      successful direct stent implantation with those with the unsuccessful procedures,
      the latter group had a higher percent of angiographically visible calcification
      at the site of the lesion (80% vs. 18%; p < 0.01). In addition, these patients
      had an increased average age (72 +/- 7 vs. 61 +/- 11 yrs; p < 0.01). The success
      rate of direct stent implantation did not depend on lesion diameter stenosis
      before PTCA. Stent dislocation was observed in 3.8% of the procedures, and a
      single case of stent embolism was seen. In conclusion, the direct stent
      implantation offers the advantages of a shortened fluoro-time, the use of fewer
      balloons, and has the potential of less ischemic stress compared to the
      conventional method of stent implantation with predilatation, if old patients
      with calcified lesions are excluded. This should be proved on a large scale in
      future studies also considering a learning curve with regard to the new method.
      Whether this new approach also reduces the restenosis rate, warrants further
      studies.

PMID- 10209834
TI  - [Pharmacological testing of the reversibility of increased pulmonary vascular
      resistance before heart transplantation with prostaglandin I2 (prostacyclin)].
AB  - An increased pulmonary vascular resistance (PVR) or an increased transpulmonary
      gradient (TPG) is a risk factor for increased 3-day and 3-month mortality after
      heart transplantation (HTx). The reversibility of increased PVR or TPG under
      pharmacologic testing is supposed to indicate a decreased probability of right
      ventricular failure/death after transplantation. We tested the response of an
      increased PVR (> 2.5 Wood units, WU) and/or of an increased TPG (> 15 mm Hg) in
      29 right heart catheterizations (thermodilution catheter) of 23 patients (54 +/-
      8 years, mean NYHA-class 3.1 +/- 0.6, ischemic n = 8, dilated cardiomyopathy n =
      15). Increasing doses of prostaglandin I2 (PGI2, mean maximum dose 13.5 +/- 6.4
      ng/kg/min) were applied stepwise over at least 10 min at the maximum dose level.
      We analyzed any dependence of the reversibility of PVR and TPG under
      prostaglandin I2 on hemodynamic values, echocardiographic parameters, demographic
      data, and laboratory findings. A decrease of PVR to a range usually accepted as
      no contraindication for HTx (< or = 4 WU) was found in each patient without
      symptomatic systemic hypotension during application of PGI2 (baseline value: 4.7
      +/- 1.3 WU, during PGI2: 2.3 +/- 0.6 WU). An unresponsive, fixed increased PVR or
      TPG was not observed using PGI2. In 62% of investigations, both PVR and TPG
      decreased below 2.5 WU and 15 mmHg, respectively. The extent of reversibility of
      PVR and TPG was individually different and did not depend on the mean pulmonary
      artery pressure, mean capillary wedge pressure, cardiac output, mean systemic
      artery pressure or echocardiographic parameters (EDD, FS, ES-distance), sodium,
      urea or bilirubin levels, medication, age of the patients or the duration of the
      disease. The baseline PVR correlated inversely with its percentile value during
      PGI2 (r = -0.76, p < 0.05). In advanced heart failure, PGI2 decreases PVR in
      ranges of lower risk concerning orthotopic HTx, without causing an intolerable
      systemic hypotension. The individual extent of reversibility of PVR and TPG under
      PGI2 is not influenced by basic hemodynamic parameters or the patient's
      demographic profile.

PMID- 10209835
TI  - [Heparin-induced thrombocytopenia type II with early aortocoronary bypass
      occlusion and stent thrombosis after PTCA of the RCA--treatment with lepirudin
      (Refludan) and abciximab (Reo pro) during recanalization of the RCA].
AB  - Heparin-induced thrombocytopenia type II (HIT type II) is the most serious
      complication of heparin treatment apart from bleeding, which is the most common
      side effect. Eleven days after coronary bypass grafting, a 71 year old patient
      showed a posterolateral myocardial infarction and a thrombocytopenia of
      80,000/microliter. This was considered a postoperative thrombocytopenia. Coronary
      angiography revealed closed venous bypass grafts. The right coronary artery (RCA)
      was revascularized by percutaneous transluminal coronary angioplasty (PTCA) and
      stent placement. During both coronary angiography and PTCA, heparin was
      administered to the patient. The platelet number did not change. Four days later
      the patient showed an inferior myocardial infarction and an AV-block III degrees
      and a syncope. The following coronary angiography revealed RCA stent occlusion.
      HIT type II was presumed and recanalization was carried out using Lepirudin
      (Refludan) as the anticoagulant. After placing the guide wire, thrombi could be
      seen in the proximal RCA. Abciximab (Reo pro), a monoclonal antibody against the
      glycoprotein IIb/IIIa receptor was additionally administered. Coronary
      angiography on the next day revealed only a small remaining thrombus. The AV
      block disappeared immediately after revascularization. The diagnosis of HIT type
      II was confirmed through heparin-induced-platelet-activation-test (Hipa-test) and
      immunoassay (PF 4/heparin-ELISA). This case report illustrates the complicated
      diagnosis of HIT type II and the successful simultaneous use of Lepirudin
      (Refludan) and Abciximab (Reo pro). The number of platelets should be checked
      daily during heparin treatment. In the case of a thrombocytopenia, the treatment
      should be stopped immediately, and Hipa-test and PF 4/heparin-ELISA should be
      carried out.

PMID- 10209836
TI  - [Diagnosis of an intramyocardial hematoma via MRI after a traumatic myocardial
      infarct].
AB  - Traumatic cardiac lesions occur in about 30% of all traumatized patients, in most
      cases they are due to traffic accidents. We report a patient who suffered from a
      traumatic anterior wall infarction following a ski accident. Consecutively, an
      extended intramyocardial hemorrhage occurred. A left ventricular pseudoaneurysm
      was considered first by echocardiography. Using MRI, an intramyocaridal
      hemorrhage could be diagnosed because of a thin myocardial border surrounding the
      hematoma. Consecutively, the patient underwent CABG surgery as well as a
      resection of the intramyocardial hematoma. This diagnosis could be manifested
      surgically and histologically.

PMID- 10209837
TI  - [Organ transplantation and quality of life].

PMID- 10209838
TI  - [Quality of life following renal transplantation in childhood].
AB  - The goal of renal transplantation is to achieve the best possible quality of life
      in patients with terminal renal failure. To evaluate some aspects of quality of
      life in patients with renal grafts during childhood of our center, data on
      medical, educational and professional rehabilitation were collected
      retrospectively. Between 1972 and 1997 135 renal transplantations had been
      performed in 123 patients below the age of 18 years. 12-year graft survival of
      patients transplanted before 1983 figured at 21% and rose to 62% during the
      following years, after introduction of cyclosporine A into the immunosuppressive
      regimen. The proportion of patients in the respective age group attending a
      secondary school (16%) was lower and of those attending elementary school (71%)
      or a school for disabled and handicapped children (11%) was higher than usual in
      the German population. But, 83% of all patients reached a school degree. After
      school 78% proceeded with a vocational training or university. 89% of patients
      completing professional training were employed at last observation as compared to
      only 60% of those who never finished a professional training. Renal replacement
      therapy starting already during the early phase of education is difficult to
      coordinate with normal schooling. Considering these health- and time-related
      obstacles, the degree of educational and professional rehabilitation of the
      patients is good. But, there is a need for special support accompanying
      educational and professional training.

PMID- 10209839
TI  - [Quality of life following liver transplantation in childhood].
AB  - Orthotopic liver transplantation is now routinely performed in infants and
      children with end-stage liver disease and acute hepatic failure. Quality of life
      after transplantation depends on organ function, cure or recurrence of the
      original liver disease, need for further medical care, and complications
      associated with immunosuppression. Physical and psychomotor development as well
      as social integration are special aspects which are important for quality of life
      considerations in children. To illustrate these aspects we will discuss the
      clinical course of some of our patients.

PMID- 10209840
TI  - [The subjective element in transplantation medicine. The importance of
      psychosocial indicators in transplantation and their effect on the quality of
      life].
AB  - The importance of psychosocial indicators for the course and the evaluation of
      organ transplantation is being more and more recognized. The following paper
      tries to point out what should be, at the present, the "state of the art" in
      psychosocial evaluation and quality of life measurement in organ transplantation.

PMID- 10209841
TI  - [Quality of life following transplantation. The impact ofa new immunosuppressive
      substance].
AB  - The improvement of quality of life is one of the major goals in the treatment of
      patients after renal transplantation. While immunosuppressive therapy is present
      in almost all of these patients, little is known about the effects of newer
      immunosuppressive agents. We therefore investigated the impact of tacrolimus on
      life quality. From November 1997 to January 1998, a questionnaire was handed out
      which focussed on physical and mental problems as well as sexual capacity and the
      attitudes towards graft, donor and transplant related side effects. 50 kidney
      graft recipients treated with tacrolimus were matched to 50 patients with a
      cyclosporine-based immunosuppression (= controls). Values are given as mean +/-
      standard deviation. Tacrolimus treated patients had a mean creatinine of 1.8 +/-
      0.8 mg/dl, as compared to 1.6 +/- 0.7 mg/dl in controls. The overall status of
      health was assessed to be good in 82% of the tacrolimus group (controls: 80%).
      38% were working full-time (controls: 20%). Only 14% of patients described their
      physical condition as poor (16% in controls). Sexual function was good in 66%
      (controls: 74%) and poor in 10% (controls: 12%). Mental function was assessed to
      be good in 92% (controls: 82%). The majority of patients felt comfortable with
      their physical, sexual and mental capabilities. This was independent from the
      immunosuppressive regimen.

PMID- 10209842
TI  - [Thoracic surgery].

PMID- 10209843
TI  - [Resection of lung metastases: long-term results and prognostic analysis based on
      5206 cases--the International Registry of Lung Metastases].
AB  - The International Registry of Lung Metastases was established in 1991 to asses
      the long-term results of pulmonary metastasectomy. The Registry has accrued 5206
      cases of lung metastasectomy, from 18 departments of thoracic surgery in Europe
      (n = 13), USA (n = 4) and Canada (n = 1). Of these patients 4572 (88%) underwent
      complete surgical resection. The primary tumor was epithelial in 2260 (43%),
      sarcoma in 2173 (42%), germ cell in 363 (7%), and melanoma in 328 (6%) patients.
      The disease-free interval was 0 to 11 months in 1729 (33%) cases, 12 to 35 months
      in 1857 (36%) and more than 36 months in 1620 (31%). Single metastases accounted
      for 2383 (46%) cases and multiple lesions for 2726 (52%). Mean follow up was 46
      months. Analysis was performed by Kaplan-Meier estimates of survival, relative
      risk of death and multivariate Cox model. The actuarial survival after complete
      metastasectomy was 36% at 5 years, 26% at 10 years and 22% at 15 years (median 35
      months); the corresponding values for incomplete resection were 13% at 5 years
      and 7% at 10 years (median 15 months). Among complete resections, the 5-year
      survival was 33% for patients with a disease free-interval of 0 to 11 months and
      45% for those with a disease-free interval of more than 36 months; 43% for single
      lesions and 27 for four or more lesions. Multivariate analysis showed a better
      prognosis for patients with germ cell tumors, disease-free interval of 36 months
      and more and single metastases. These results confirm that lung metastasectomy is
      a safe and potentially curative procedure.

PMID- 10209845
TI  - [Lymph node dissection during surgery for lung cancer. Solely staging or
      therapy?].
AB  - The accuracy of staging of lung cancer is reflected by the extent of mediastinal
      lymph node sampling. The more extensively a patient is tested, the more likely
      there will be the accurate N-stage diagnosed. Adequate lymph node dissection
      during surgery for lung cancer therefore requires complete dissection of all
      three ipsilateral mediastinal compartments including the infracarinal region.
      Additional contralateral mediastinal lymph node exploration may not be justified.
      A direct therapeutic effect of mediastinal lymph node removal may be attributed
      to the prevention of local tumor growth. However, its overall prognostic
      significance remains unclear because it must be assumed that proven tumor within
      the mediastinal lymph nodes reflects the state of tumor generalization that may
      not be cured by localized therapeutic means. New systemic interventions are
      clearly warranted to significantly improve prognosis in stage II and III lung
      cancer patients.

PMID- 10209844
TI  - [The value of prognostic factors in patients who underwent a resection of
      pulmonary metastases].
AB  - 155 patients were operated on pulmonary metastases in Jena during the period from
      1.1.1984 to the 31.12.1994. The findings of 151 patients were analysed. 128
      patients suffered from a carcinoma, 15 from a sarcoma, 6 from a malignant
      melanoma and 2 from a Wilms-tumor. The prognostic factors discussed in the
      international publications at present were investigated in those patients.
      Significant differences in the long-term survival were found for the following
      features: a possible radical resection, the tumor entity, the site, the histology
      and the grading of the primary tumor, the size and the site of the metastases and
      the resection of recurrent metastases. Tendencies are described for the type of
      dissemination and the staging of the primary tumor, the site of the pulmonary
      metastases in the lung lobes, solitary extrapulmonary metastases and more than 6
      lung metastases. In addition patients who showed metastases of a renal cell
      carcinoma are considered separately.

PMID- 10209846
TI  - [Thoracoscopy versus thoracotomy. The dilemma of the comparison and its meaning
      for quality assurance in thoracic surgery].
AB  - The need for scientific investigation into the benefits of thoracoscopy in
      comparison to thoracotomy as well as State intervention to assure quality in the
      field of surgery motivated the members of the commission of endoscopic surgery of
      the German Society of Thoracic Surgery to conduct a pilot project at their
      hospitals. This pilot project was expected to analyse data on the outcome and a
      selection of variables concerning trauma and postoperative quality of life of
      some 400 patients treated between 8/95 and 10/95 at 5 thoracic surgical clinics.
      On completion of the pilot project the course of 141 patients undergoing
      different thoracic operations at 4 thoracic surgery departments had been
      documented to various degrees. 60 patients for various indications received a
      thoracoscopy, 72 a thoracotomy. In 9 patients thoracoscopy was converted to
      thoracotomy (6.4%). Eight of the 141 patients died in the postoperative course
      (5.7%), overall morbidity was 15.6%. There was a slight but statistically not
      significant difference concerning mortality and morbidity in favor of
      thoracoscopy (1.7 vs. 9.7% and 10 vs. 19.4%). But, there was a selection of
      malignant diseases, higher age and high risk patients towards thoracotomy. In
      subgroups of patients undergoing operations not bigger than the resection of
      three lung wedges only time of operation and length of incision revealed to be
      significantly shorter for thoracoscopy (69(25-190) min vs. 128(24-240)min, p =
      0.0013; 6(4-8)cm vs. 23(12-35)cm, p = 0.0001). Borderline significance was
      reached by the Spitzer-Index in advantage for thoracoscopy (8(2-10)points vs. 7(0
      10)points, p = 0.0728). Thoracotomy and thoracoscopy are access procedures used
      with different indications in different patients. Differences concerning trauma
      and quality of life if present are marginal and will need studies to be outlined.
      Quality assurance in thoracic surgery using a standardized documentation will not
      succeed under the given circumstances.

PMID- 10209847
TI  - [Pulmonary nodule. The surgeon's approach].
AB  - Malignancy must be suspected with any pulmonary nodule detected on radiologic
      examination of the chest until its benign origin has been proven. This requires
      further evaluation of the patient. The non invasive diagnostic steps include
      patient's history, clinical examination, lung function testing, and standard
      radiographs and a computed tomography (CT) of the chest. Based on these findings
      the presumed diagnosis claims the next appropriate diagnostic steps. If lung
      cancer is the most likely diagnosis and lung function testing revealed that the
      patient is a candidate for lung resection than surgery may be the next step.
      Preoperative proof of the histologic diagnosis is not mandatory. It is the less
      required the more surgery may be curative. If curative resectability is indoubt
      or the patient is not candidate for lung resection than histologic diagnosis
      should be confirmed prior to introduction of radiotherapy or chemotherapy by the
      least invasive procedure (bronchoscopy < lymph node biopsy < needle biopsy <
      mediastinoscopy/-tomy < VATS). If metastatic disease must be suspected, staging
      should be completed as required for the primary malignancy. With local recurrence
      and other metastases excluded the number of pulmonary nodules detected on CT scan
      points to the appropriate surgical approach. In case of a solitary nodule or
      multiple but resectable nodules, complete (wedge) resection with lymph node
      dissection through a lateral thoracotomy will be the procedure of choice. With
      multiple and unresectable nodules, surgery allows definitive diagnosis and
      videothoracoscopy affords the opportunity to accomplish wedge resection of the
      lung along with low morbidity. When lesions are deemed indeterminate, definitive
      diagnosis should nevertheless be attempted. If there is no history of malignancy
      routine evaluation for such in asymptomatic patients is not indicated. With small
      nodules (less than 3 cm in diameter) located in the periphery of the lung,
      videothoracoscopic wedge resection is indicated without preoperative sputum
      cytology, bronchoscopy or transthoracic needle biopsy. The histologic diagnosis
      obtained by intraoperative frozen sections than determines the further surgical
      approach. Benign lesion: completion of surgery; lung cancer: proceed to
      thoracotomy with anatomic lung resection and mediastinal lymph node resection;
      metastatic disease: completion of surgery and further search for primary
      malignancy.

PMID- 10209848
TI  - [Surgical and functional results after surgical lung volume reduction in 94
      patients with severe emphysema].
AB  - Lung volume reduction (LVR) is a new surgical approach designed to relieve
      shortness of breath and improve exercise tolerance in patients with severe lung
      emphysema. The aim of this study was to analyse surgical results and changes in
      the lung function, gas exchange, exercise tolerance and degree of dyspnoea until
      two years after LVR. From June 1994 to September 1997 ninety-four patients (31
      women and 63 men, mean age 64 [35-79] years) with severe emphysema (12 with alpha
      1-Pi-deficiency) underwent unilateral (n = 24) or bilateral (n = 70) LVR. 92 from
      94 patients were extubated immediately after surgery. 30 days mortality was 2.2%
      (2/94), 90 days 3.3% (3/94) respectively. Most common postoperative complications
      were pneumonia (n = 15, 16%) and air leakage longer than 7 days (n = 22, 23.4%).
      One month after surgery there was a significant increase in forced expiratory
      vital capacity after one second (FEV1 59%) and significant decrease in total lung
      capacity (TLC 19%) and residual volume (RV 28%). Also significant changes were
      observed in paO2, paCO2, 6-minute walking distance, dyspnoea score and
      respiratory muscle function. Two years after LVR lung function tests in patients
      with smokers emphysema showed the benefit to be maintained (high responders).
      Patients with alpha 1-Pi-deficiency showed 6 to 12 months after surgery a
      remarkable deterioration of functional data (low responders). In selected
      patients with severe emphysema surgical LVR shows significant improved pulmonary
      function, gas exchange, dyspnoea and walking distance. The results are better
      after bilateral operation. Patients selection, rehabilitation program and
      interdisciplinary care resulted in a low operative morbidity and mortality.

PMID- 10209849
TI  - [Prostanoid release and lipid peroxidation in patients with thoracic trauma].
AB  - There is compelling data from recent clinical studies on the impact of damage to
      the lung on the fate of traumatized patients. The lung reacts with a tremendous
      release of inflammatory mediators, but, on the other hand, this organ's ability
      in inactivating those factors is simultaneously attenuated. What is more, it is
      well known, that there often are no clinical signs of pulmonary dysfunction
      despite severe lung injury in the early posttraumatic phase. Therefore, in this
      prospective clinical study the following questions were addressed: (i) Is there
      any difference of the patients' lung response whether or not the (poly)trauma is
      associated with damage to the chest, (ii) either in the early or the late
      posttraumatic phase, and (iii) is there any marker that may prove to be a
      (significant) predictor of poor overall outcome? METHODS: Upon approval of the
      local IRB/EC, 35 patients (pts) were enrolled who suffered from multiple
      injuries. The first blood samples were drawn at admission, then every two hours
      and in daily intervals. The plasma concentrations of following mediators were
      analyzed: prostanoids (PGI2, TxA2, PGE2, PGF2 alpha) and products of O2-radicals
      (malondialdehyde, conjugated dienes). All values were calculated on the basis of
      the actual plasma protein content to eliminate fluid-induced dilution effects.
      Subsets of pts were performed according to the different injury pattern: (i) pre
      dominantly thoracic trauma (TX, n = 9); (ii) polytrauma with (PTX, n = 19), and
      (iii) without (PT, n = 7) damage to the lung. RESULTS: As early as at admission,
      all pts revealed a severity-independent increase (p < 0.01) in most mediators'
      plasma levels. The pattern-related inflammatory response was most pronounced in
      casualties who had experienced thoracic trauma irrespective of whether it was
      combined with polytrauma. Within 1 to 3 days, the plasma levels of most mediators
      but PGE2 and MDA (all pts) as well as PGF2 alpha (PTX-group) normalized. The
      reactions of the lipid peroxidation products admitted of no group-differences.
      CONCLUSIONS: Although there was a pattern-related release of (most) prostanoids
      which was rather pronounced in polytrauma associated with damage to the lung, we
      failed in proving any predictive marker to specifically estimate outcome, so far.

PMID- 10209850
TI  - [Intraabdominal cystic lymphangioma in childhood. Report of 2 cases].
AB  - Intraabdominal cystic lymphangiomas are rare tumor-like lesions, predominantly
      found in the pediatric age group, but also in juveniles or young adults.
      Lymphangiomas are always benign and do not recur after complete excision. In this
      paper we report on two 4-year old children with a history of abdominal discomfort
      due to large cystic lymphangiomas, the diagnostic procedure and the definite
      surgical therapy by complete excision. While the histogenesis of cystic
      lymphangiomas is generally discussed controversely, in one of our cases there is
      some evidence that the lesion developed in fetal lifetime in combination with a
      scar of the intestinal wall of the ileum.

PMID- 10209851
TI  - [Use of the harmonic scalpel (Ultracision) in laparoscopic antireflux surgery].
AB  - Gastroesophageal reflux disease can effectively be treated by laparoscopic
      fundoplication. A new multifunctional device has recently been introduced,
      Ultracision (UC), which can be expected to be especially effective in
      laparoscopy. Since 9/1995 laparoscopic fundoplication is being performed at our
      institution. We routinely divide the "short-gastric vessels" and have been using
      clip-appliers and Endo-GIAs before dividing the vessels with endo-scissors. Since
      2/1997 we also use the UC, which applies ultrasonic energy to cause denaturing of
      proteins and subsequent hemostasis and dissection. This open, non-randomized
      study compares operative time, intra- and postoperative complications and
      conversion rates as well as costs of both methods. Between 2/1997 and 12/1997 20
      consecutive patients received a floppy Nissen fundoplication by 2 surgeons. In 8
      patients clips/EndoGIA were used (m:w = 5:3, mean age 52 years [33-69]), in 12
      patients UC (m:W = 10:2, 53 years [25-74]) was used. 2 patients in each group had
      had previous open abdominal surgery. In the first group 2 procedures had to be
      converted to open surgery (1 bleeding, 1 anatomical problem), median operative
      time was 214 min (135-360). In the UC group all procedures were completed
      laparoscopically, median operative time 132 min (75-240). Postoperative major
      complication and mortality rates were 0 in both groups. Use of the harmonic
      scalpel reduced operative time and costs without increasing conversion rates and
      perioperative complications.

PMID- 10209852
TI  - [Breast surgery].

PMID- 10209853
TI  - [100 years of the Wertheim operation--Ernst Wertheim between myth and reality].
AB  - 100 years ago, on November 16, 1898, Ernst Wertheim performed the first radical
      abdominal hysterectomy for cervical cancer wearing his name. In this historical
      survey the life story of Wertheim is described involving morally questionable
      behaviours, misconceptions to radiation therapy, and problems regarding his
      obstetrical teaching. In context to the Wertheim-operation the vaginal radical
      hysterectomy developed by Schuchardt and Schauta and the radiation therapy of
      cervical cancer in the Wertheim-era are discussed.

PMID- 10209854
TI  - [The clinical importance of keratin 18 in breast cancer].
AB  - OBJECTIVE: This study was performed to determine the prognostic significance and
      the biological function of the structure protein keratin 18 (K18) in a group of
      patients with breast cancer. MATERIAL AND METHODS: Paraffin sections from the
      primary tumors in 80 patients with breast cancer were examined for the expression
      of K18 by immunohistochemical staining with the monoclonal antibody CK2. The
      intensity of the expression measured by an immune reactive score (IRS) was
      compared with clinicopathological variables and follow-up data up to 10 years.
      Additionally K18 expression in different human breast cancer cell lines with well
      defined metastatic behavior were investigated to confirm the clinical data.
      RESULTS: A marked positive staining was observed in 13 (16.2%) women. Mortality
      rate in this group was 7.7% and 46.3% in the group with a low K18 expression. The
      recurrence rate was with 15.4% significantly lower in the positive group than in
      the negative group with 56.7%. Irrespective of the morphological tumor stage,
      almost all patients with strong K18 expression were still free of disease after
      10 years. This clinical finding is supported by observations in cell cultures.
      CONCLUSIONS: In our collective K18 expression was found to be an independent and
      significant predictor for disease-free and overall survival.

PMID- 10209856
TI  - [Quantitative bone ultrasound (QUS) of the heel bone for diagnosis of
      osteoporosis in the general community].
AB  - OBJECTIVE: The aim of the present study was to investigate how quantitative bone
      ultrasonometry (QUS) can detect patients at risk for osteoporosis in a general
      community. MATERIAL AND METHODS: 260 women aged 63 +/- 10 were examined using
      questionnaire, osteological history and QUS (Achilles+). RESULTS: The most
      frequent osteoporosis risk factors were: no estrogens, no sports and osteoporosis
      within the family. Risk-patients had lower QUS values compared to persons without
      risk-factors. There was a negative correlation of ultrasound parameters with age,
      but not with height or weight. Patients showed a mean loss of body height of -1.2
      +/- 1.8 cm versus height in passports, which was positively correlated with QUS.
      30% of patients with osteoporosis (T = -2.3 +/- 1.4 SD) had lower QUS than those
      without (T = -1.4 +/- 1.4 SD). 22% have had a atraumatic fracture (T = -2.5 +/-
      1.4 SD), 12 patients had suffered a hip fracture (T = -2.8 +/- 1.8 SD) and 15
      patients had a vertebral fracture (T = -2.6 +/- 1.6 SD). Patients on estrogens
      had T = -1.5 +/- 1.4 SD, which was higher than in those without HRT (T = -2.0 +/-
      1.3 SD, p < 0.05). CONCLUSIONS: We conclude from this study that risk patients
      for osteoporosis can be detected within the community using QUS. QUS is able to
      detect differences between treated and untreated and can be used in clinical
      practice to manage patients with osteoporosis risk.

PMID- 10209855
TI  - [Value of clinically established MRI procedures concerning the pretherapeutic
      evaluation of maximal tumor diameter in primary or recurrent cervix cancer in
      relation to palpation findings and histopathologic whole mount specimens].
AB  - OBJECTIVE: The maximal tumor diameter of cervical cancer is one of the most
      important prognosis factors concerning patients' survival. The purpose of this
      study was to investigate the efficiency of different MRI-procedures in relation
      to clinical palpation concerning pretherapeutic tumor diameter assessment.
      MATERIAL AND METHODS: Thirty-one patients with biopsy proven primary cervical
      cancer and its recurrence (n = 10), respectively, underwent dynamic and
      conventional MRI before further treatment. The results of maximal tumor diameters
      were compared to palpatory findings and then correlated to the whole mount
      specimen as gold standard. RESULTS: The contrast-enhanced dynamic and T2-weighted
      MRI allows a significantly better (p < 0.05) assessment of maximal tumor diameter
      of cervical cancer than the conventional T1-weighted MRI. The T2-weighted MRI
      showed the highest correlation (r = 0.83) in respect to the whole mount specimen
      up to FIGO-IIB disease. The contrast-enhanced dynamic MRI and the palpation were
      characterized by the highest correlation coefficients of r = 0.77, r = 0.70
      respectively, in advanced cervical cancer > FIGO-IIB disease. CONCLUSIONS: The
      MRI procedures offer no evident advantage in relation to clinical palpation to
      determine the maximal tumor diameter of cervical cancer or its recurrency and
      seems not to be indicated generally.

PMID- 10209857
TI  - [Rating of transvaginal sonography in the evaluation of postmenopausal bleeding].
AB  - OBJECTIVE: The purpose of this study was to evaluate transvaginal ultrasonography
      (TVS) in differential diagnosis of vaginal bleedings in postmenopausal patients.
      MATERIAL AND METHODS: Between January 1990 and December 1996, 1198 postmenopausal
      patients with vaginal bleedings were sent to our clinic for a histological
      evaluation. Eight hundred and seventy-nine patients (73.4%) were preoperatively
      scanned by transvaginal probe, and endometrial thickness (< 5, 5-7, 8-10, > 10
      mm) was measured. RESULTS: Atrophy was found in 46.3%, endometrial polyps in
      19.8%, endometrial cancer in 17.5%, and hyperplasia in 6.7%. An endometrial
      thickness of lower than 5 mm (p < 0.0001) was shown in TVS patients with atrophy
      in 71%, with endometrial polyps in 10.9%, with endometrial cancer in 3.9% and
      hyperplasia in 6.8%. In 55.2% of these eases with endometrial cancer the
      preoperatively estimated thickness was 10 mm or more. The additionally
      morphologic examination in cases with an endometrium smaller than 5 mm was false
      positive in 75% (9/12). Thus an endometrial thickness of > 5 mm had a sensitivity
      of 92.5%, specificity of 71.0%, positive and negative predictive value of 75.6,
      respectively 90.9% for the detection of endometrial pathology. CONCLUSIONS: TVS
      allows the detection of an endometrial pathology in the vast majority of patients
      with postmenopausal bleedings. In cases with a single postmenopausal bleeding and
      an endometrium smaller than 5 mm we recommend expectative procedures with
      repeated ultrasound examination of the endometrium.

PMID- 10209858
TI  - [Lower leg compartment syndrome after prolonged gynecologic surgeries in
      lithotomy position].
AB  - OBJECTIVE: How to prevent severe complications of lower leg compartment syndrome
      following gynecologic operations in the lithotomy position? MATERIAL AND METHODS:
      Two cases of lower leg compartment syndrome following long lasting gynecologic
      operations are presented. RESULTS: Early diagnosis by clinical signs, measurement
      of compartment pressure and creatine kinase activity and undelayed surgical
      intervention can avoid acute renal failure due to rhabdomyolysis and damage of
      neuromuscular function. CONCLUSIONS: Early diagnosis and undelayed surgical
      intervention can prevent severe complications of lower leg compartment syndrome
      following gynecologic operations in the lithotomy position.

PMID- 10209859
TI  - [Intra-abdominal hemangiopericytoma: an unexpected finging during laparotomy].
AB  - Two cases of intraabdominal hemangiopericytoma are reported. 1. A 32-year-old
      patient underwent laparotomy because of a tumor arising from the greater omentum.
      Histological examination showed benign hemangiopericytoma. 2. In a 57-year-old
      women laparotomy revealed a tumor attached to the Omentum maius. Histological
      examination confirmed the diagnosis of malignant hemangiopericytoma. In spite of
      radical operation the patient died 9 months later. Until now only a few case
      reports exist about the occasional finding of hemangiopericytoma when
      gynecological disease was suspected. If the tumor is malignant prognosis does not
      seem to be improved by the additional radio- or chemotherapy.

PMID- 10209861
TI  - [Assessment of mammography screening and its introduction in Germany in the
      Statutory Early Diagnosis Program].
AB  - Malmo, in the south of Sweden, has, over the past 15 years, achieved a reduction
      in the mortality rate of 10% as a result of adjuvant drug treatment (adjuvant
      chemo- and hormone therapy). The drop in the mortality rate by means of a quality
      assured early diagnosis programme, reduces the mortality rate for breast cancer
      by 34% so that in South Sweden these methods have reduced the death rate for
      breast cancer by a total of 44% although the incident rate has increased by
      1.25%. It follows that a quality assured early diagnosis programme is by far the
      most effective method of reducing the mortality rate for breast cancer, whereby
      breast cancer constitutes the main cause of death from cancer in women. The
      effectiveness of early diagnosis is dependent on experience with these methods
      whereby the learning curve, even in the case of specialists, does not reach a
      maximum until there has been at least 6-8 years experience and a minimum of 8000
      patients have been seen. A reduction in the mortality rate can only be achieved
      if a large number of the population takes part (in Sweden, 89% of women
      contacted) and only applies to the age group 40-70. In the case of younger women
      (40-50 years) the reduction in the death rate in Sweden lies at 30%. For cost
      benefit reasons this age group has not yet been recommended for routine screening
      in Sweden, apart from in clinical studies. Screening is only effective with
      complete quality control of technical equipment and personnel as stipulated in
      the European guidelines for screening mammography (August 1997 edition, EU
      Commission (EUREF). The risks of radiation exposure, with a threshold value of 5
      mGy per breast (X-ray in two planes), is so minimal that it is as yet not
      measurable. The induction of breast cancer through annual screening mammography
      is estimated theoretically at 4 indicated cases of breast cancer to 1 million
      female years. Theoretically these induced cases of breast cancer can be cured by
      early diagnosis. A reduction in the mortality rate of 34% is a tremendous
      advantage for women. Since breast cancer is the main cause of death in women
      between the ages of 38 and 51 and screening considerably cheaper than other
      preventive measures (cervical smear, dialysis in kidney disease, safety belts,
      medication to lower cholesterol levels) the introduction of quality assured
      screening is an essential priority towards improving the health of women in
      society today. It has been proved (Netherlands) that the cost of screening is far
      lower than the expense incurred in the treatment of women in the metastatic stage
      of their cancer illness before death.

PMID- 10209860
TI  - [Persistent anovulation following laparoscopic electrocoagulation of the ovarian
      surface in a patient with polycystic ovary syndrome (PCOS)].
AB  - We report on a 32-year-old woman with polycystic ovarian syndrome (PCOS) who
      showed no ovarian reaction (oestradiol increase, leading follicle) to clomiphene
      and gonadotropin stimulation before and after laparoscopic electrocoagulation of
      the ovarian surface (LEOS) although hormone values (LH-FSH ratio,
      androstenedione) after LEOS were within normal range. The case is discussed in
      terms of the literature.

PMID- 10209862
TI  - [Steps towards a hospital information system: illustrated by the example of the
      medical setting of the Westphalian Wilhelms University of Munster].
AB  - Implementing hospital information systems for an efficient application of
      electronic data processing requires the integration of previously introduced
      departmental systems, which traditionally have been designed only from the
      viewpoint of an isolated hospital department. Those efforts have to be
      accompanied by a parallel implementation of a hospital-wide network and the
      introduction of PC workstations on clinical wards and in outpatient clinics. In
      this paper currently ongoing efforts at the University Hospital of Munster are
      presented in order to illustrate how such integration efforts can improve
      communication and information retrieval in all clinical areas of a hospital.

PMID- 10209863
TI  - Matrix-assisted laser desorption/ionization mass spectrometry of neutral and
      acidic oligosaccharides with collision-induced dissociation.
AB  - Using ribonuclease B and human alpha 1-acid glycoprotein (AGP) as model
      glycoproteins, matrix-assisted laser desorption/ionization (MALDI) mass
      spectrometry with collision-induced dissociation (CID) is validated here as an
      effective tool for oligosaccharide sequencing. The spectra acquired for high
      mannose and complex oligosaccharide structures show characteristic fragments
      resulting from cleavages of the glycosidic bonds and a few cross-ring cleavages.
      Esterification of the sialic acid residues is essential in stabilizing the acidic
      N-linked oligosaccharides. An important analytical feature observed in all
      acquired spectra is the occurrence of cleavages on the same antenna up to the
      branching point, as deduced from the absence of fragmentation due to the
      simultaneous cleavages on two or more antennas.

PMID- 10209864
TI  - Structure of the enzymatically synthesized fructan inulin.
AB  - Construction, purification and characterization of a fusion protein of maltose
      binding protein of Escherichia coli and the fructosyltransferase of Streptococcus
      mutans is described. With the purified protein, in vitro synthesis of inulin was
      performed. The obtained polysaccharide was characterized by high-performance size
      exclusion chromatography (HPSEC) and static light scattering (SLS) in dilute
      aqueous and dimethyl sulfoxide solution. For all samples very high molecular
      weights between 60 x 10(6) and 90 x 10(6) g/mol and a remarkable small
      polydispersity index of 1.1 have been determined. Small root-mean-square radii of
      gyration point to a compact conformation in dilute solution. No difference
      between native and enzymatically synthesized inulin was observed by X-ray powder
      diffraction and thermoanalysis of solid samples.

PMID- 10209865
TI  - Authentic standards for the reductive-cleavage method: the positional isomers of
      partially methylated and acetylated or benzoylated 1,5-anhydro-L-arabinitol.
AB  - Described herein is the synthesis of the eight positional isomers of methylated
      and acetylated or benzoylated 1,5-anhydro-L-arabinitol. The compounds were
      generated simultaneously from 1,5-anhydro-L-arabinitol by sequential partial
      methylation and benzoylation and isolated in pure from by high-performance liquid
      chromatography. The desired acetates were obtained by debenzoylation and
      acetylation of the pure isomers. Reported herein are the 1H NMR spectra of the
      benzoates and the electron-ionization mass spectra of the acetates and the tri-O
      methyl derivative. Also reported for the acetates and the tri-O-methyl derivative
      are their linear temperature-programmed gas-liquid chromatography retention
      indices on three different capillary columns.

PMID- 10209866
TI  - Transglycosylation reactions of Bacillus stearothermophilus maltogenic amylase
      with acarbose and various acceptors.
AB  - It was observed that Bacillus stearothermophilus maltogenic amylase cleaved the
      first glycosidic bond of acarbose to produce glucose and a pseudotrisaccharide
      (PTS) that was transferred to C-6 of the glucose to give an alpha-(1-->6)
      glycosidic linkage and the formation of isoacarbose. The addition of a number of
      different carbohydrates to the digest gave transfer products in which PTS was
      primarily attached alpha-(1-->6) to D-glucose, D-mannose, D-galactose, and methyl
      alpha-D-glucopyranoside. With D-fructopyranose and D-xylopyranose, PTS was linked
      alpha-(1-->5) and alpha-(1-->4), respectively. PTS was primarily transferred to C
      6 of the nonreducing residue of maltose, cellobiose, lactose, and gentiobiose.
      Lesser amounts of alpha-(1-->3) and/or alpha-(1-->4) transfer products were also
      observed for these carbohydrate acceptors. The major transfer product to sucrose
      gave PTS linked alpha-(1-->4) to the glucose residue. alpha,alpha-Trehalose gave
      two major products with PTS linked alpha-(1-->6) and alpha-(1-->4). Maltitol gave
      two major products with PTS linked alpha-(1-->6) and alpha-(1-->4) to the
      glucopyranose residue. Raffinose gave two major products with PTS linked alpha-(1
      ->6) and alpha-(1-->4) to the D-galactopyranose residue. Maltotriose gave two
      major products with PTS linked alpha-(1-->6) and alpha-(1-->4) to the nonreducing
      end glucopyranose residue. Xylitol gave PTS linked alpha-(1-->5) as the major
      product and D-glucitol gave PTS linked alpha-(1-->6) as the only product. The
      structures of the transfer products were determined using thin-layer
      chromatography, high-performance ion chromatography, enzyme hydrolysis,
      methylation analysis and 13C NMR spectroscopy. The best acceptor was gentiobiose,
      followed closely by maltose and cellobiose, and the weakest acceptor was D
      glucitol.

PMID- 10209867
TI  - The use of fluoro- and deoxy-substrate analogs to examine binding specificity and
      catalysis in the enzymes of the sorbitol pathway.
AB  - The carbohydrate specificity of the two enzymes that catalyze the metabolic
      interconversions in the sorbitol pathway, aldose reductase and sorbitol
      dehydrogenase, has been examined through the use of fluoro- and deoxy-substrate
      analogs. Hydrogen bonding has been shown to be the primary mode of interaction by
      which these enzymes specifically recognize and bind their respective polyol
      substrates. Aldose reductase has broad substrate specificity, and all of the
      fluoro- and deoxysugars that were examined are substrates for this enzyme.
      Unexpectedly, both 3-fluoro- and 4-fluoro-D-glucose were found to be better
      substrates, with significantly lower K(m) and higher Kcat/K(m) values than those
      of D-glucose. A more discriminating pattern of substrate specificity is observed
      for sorbitol dehydrogenase. Neither the 2-fluoro nor the 2-deoxy analogs of D
      glucitol were found to be substrates or inhibitors, suggesting that the 2
      hydroxyl group of sorbitol is a hydrogen bond donor. The 4-fluoro and 4-deoxy
      analogs are poorer substrates than sorbitol, also implying a binding role for
      this hydroxyl group. In contrast, both 6-fluoro- and 6-deoxy-D-glucitol are very
      good substrates for sorbitol dehydrogenase, indicating that the primary hydroxyl
      group at this position is not involved in substrate recognition by this enzyme.

PMID- 10209868
TI  - Structural studies of the extracellular beta-D-glucans from Phytophthora
      parasitica Dastur.
AB  - Several extracellular glucans have been isolated from Phytophthora parasitica
      Dastur, a phytopathogenic fungus of the carnation. These polysaccharides consist
      of a mixture of (1-->3)(1-->6)-beta-D-glucans whose molecular masses varied from
      1 x 10(4) to 5 x 10(6) Da. All of these polysaccharides have a main chain of beta
      (1-->3)-linked D-glucose residues substituted with mono-, di- and oligo
      saccharidic chains attached through (1-->6) linkages.

PMID- 10209869
TI  - Copper(II) binding to tobramycin: potentiometric and spectroscopic studies.
AB  - Protonation and Cu(II) binding by tobramycin, an aminoglycosidic antibiotic, was
      studied by potentiometry and UV-vis, CD and EPR spectroscopies. A range of
      mononuclear complexes of a general formula CuHnL was found, with n between 3 and 
      2. Tobramycin anchors Cu(II) with an ?NH2, O-? chelate of the C-ring of its
      molecule. The amino and hydroxyl groups of the A-ring of tobramycin also
      participate in the binding at pH 7 and higher. The resulting structure involves
      both terminal aminosugar rings but eliminates the donors of the central
      streptamine unit from the coordination. A comparison between tobramycin and its
      close analog, kanamycin B [M. Jezowska-Bojczuk, W. Bal and H. Kozlowski, Inorg.
      Chim. Acta, 275-276 (1998) 541-545] reveals the importance of the A3-OH group for
      the binding properties of these aminoglycosides.

PMID- 10209871
TI  - Rapid identification of the new anabaenopeptin G from Planktothrix agardhii HUB
      011 using matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry.
AB  - Toxic water blooms from cyanobacteria in lakes and rivers are a worldwide
      phenomenon. A new technique is presented for the rapid detection of toxic and
      nontoxic blooms. Matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOFMS) was employed to identify mainly peptide metabolites
      (microcystins, anabaenopeptins, cyanopeptolins, microviridins, microginins and
      aeruginosins) from microgram quantities of prepared cells within minutes. The
      spectra show the presence of peptides in strains or water blooms simultaneously.
      A new compound has been identified using the post source decay (PSD) and
      collision induced dissociation (CID) mode. This new compound has been defined as
      anabaenoeptin G. The potential of the method for screening of various secondary
      metabolite producers for defined products including antibiotics is discussed.

PMID- 10209870
TI  - Homogeneous sample preparation for automated high throughput analysis with matrix
      assisted laser desorption/ionisation time-of-flight mass spectrometry.
AB  - This work presents a simple method for obtaining homogeneous sample surfaces in
      matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry
      (MALDI-TOFMS) for the automated analysis of peptides and proteins. The sample
      preparation method is based on applying the sample/matrix mixture onto a pre
      deposited highly diluted matrix spot. The pre-deposited crystals act as seeds for
      the new sample containing crystals which become much smaller in size and more
      evenly distributed than with conventional methods. This 'seed-layer' method was
      developed, optimised and compared with the dried-droplet method using peptides
      and proteins in the 1000-20,000 Da range. The seed-layer method increases the
      surface homogeneity, spot to spot reproducibility and sample washability as
      compared with the commonly used dried-droplet method. This methodology is
      applicable to alpha-cyanohydroxycinnamic acid, sinapinic acid and ferulic acid,
      which all form homogeneous crystal surfaces. Within-spot variation and between
      spot variation was investigated using statistics at a 95% confidence level (n =
      36). The statistical values were generated from more than 5000 data points
      collected from 500 spectra. More than 90% of the sample locations results in high
      intensity spectra with relatively low standard deviations (RSDs). Typically
      obtained data showed an RSD of 19-35% within a sample spot as well as in-between
      spots for proteins, and an RSD of < or = 50% for peptides. Linear calibration
      curves were obtained within one order of magnitude using internal calibration
      with a point-RSD of 3% (n = 10). The sample homogeneity allows mass spectra
      (average of 16 laser shots) to be obtained on each individual sample within 15
      sec, whereby a 100 spot target plate can be run in 25 min. High density target
      plates using the seed-layer method were prepared by spotting approximately 100
      picoliter droplets onto the target, resulting in sample spots < or = 500 microns
      in diameter using a flow-through piezo-electric micro-dispenser. By using this
      automated sample preparation step lower standard deviations are obtained in
      comparison to manually prepared samples.

PMID- 10209872
TI  - Removal of sodium dodecyl sulfate from protein samples prior to matrix-assisted
      laser desorption/ionization mass spectrometry.
AB  - Sodium dodecyl sulfate (SDS) is widely used for protein solubilization and for
      separation of proteins by SDS polyacrylamide gel electrophoresis (SDS-PAGE).
      However, SDS interferes with other techniques used for characterization of
      proteins, such as mass spectrometry (MS) and amino acid sequencing. In this
      paper, we have compared three procedures to remove SDS from proteins, including
      chloroform/methanol/water extraction (C/M/W), cold acetone extraction and
      desalting columns, in order to find a rapid and reproducible procedure that
      provides sufficient reduction of SDS and high recovery rates for proteins prior
      to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOFMS). A 1000-fold reduction of SDS concentration and a protein recovery
      at approximately 50% were obtained with the C/M/W procedure. The cold acetone
      procedure gave a 100-fold reduction of SDS and a protein recovery of
      approximately 80%. By using desalting columns, the removal of SDS was 100-fold,
      with a protein recovery of nearly 50%. Both the C/M/W and the cold acetone
      methods provided sufficient reduction of SDS, high recovery rates of protein and
      allowed the acquisition of MALDI spectra. The use of n-octyl-beta-D
      glucopyranoside in the protein sample preparation enhanced the MALDI signal for
      protein samples containing more than 2 10(-4)% SDS, after the C/M/W extraction.
      Following the cold acetone procedure, the use of n-octylglucoside was found to be
      necessary in order to obtain spectra, but they were of lower quality than those
      obtained with the C/M/W method, probably due to higher residual amounts of SDS.

PMID- 10209873
TI  - Simultaneous determination of dimethylarsinic acid and monomethylarsonic acid
      after derivatization with thioglycol methylate by gas chromatography/mass
      spectrometry.
AB  - A gas chromatography/mass spectrometry (GC/MS) method has been developed to
      determine two methylated arsenic species in human urine samples. The yield of
      derivatization for dimethylarsinic acid (DMA) and monomethylarsonic acid (MMA)
      using thioglycol methylate (TGM) was measured. The detection limit for the
      derivatized DMA and MMA using the GC/MS method are 0.95 and 0.8 ng cm-3,
      respectively. This simple and rapid method has good precision and accuracy.
      Fragmentation routes of derivatized MMA and DMA are suggested on accurate mass
      measurements.

PMID- 10209874
TI  - A strategy for rapid and efficient sequencing of Lys-C peptides by matrix
      assisted laser desorption/ionisation time-of-flight mass spectrometry post-source
      decay.
AB  - A modification procedure for Lys-C peptides is described which simplifies the
      correct assignment of the amino acid sequence. Release of the C-terminal lysine
      from Lys-C peptides by carboxypeptidase B and subsequent N-terminal acetylation
      of the resulting peptides leads to predictable shifts of the C- and N-terminal
      fragment ions in Matrix-assisted laser desorption/ionisation time-of-flight post
      source decay mass spectra and facilitates the correct assignment of mostly
      complete amino acid sequences for oligopeptides. The derived sequences of
      peptides from unknown proteins were used to search in databases for homologous
      protein sequences. Our method was applied to an unknown protein isolated from
      eggs of Drosophila melanogaster, resulting in the identification of a peptidyl
      prolyl cis-trans-isomerase.

PMID- 10209875
TI  - Determination of anabolic steroids by gas chromatography/negative-ion chemical
      ionization mass spectrometry and gas chromatography/negative-ion chemical
      ionization tandem mass spectrometry with heptafluorobutyric anhydride
      derivatization.
AB  - A gas chromatography/mass spectrometry (GC/MS) method is described which uses
      negative ion chemical ionization (NCI) and tandem mass spectrometry (MS/MS) for
      the determination of eight anabolic steroids in human urine. Eight anabolic
      steroids were derivatized by heptafluorobutyric anhydride (HFBA), and were
      determined using GC/NCI-MS and GC/NCI-MS/MS. The linear correlation coefficients
      for calibration in NCI-MS/MS were in the range 0.9880-0.9988. This method of
      derivatization with HFBA for use with GC/NCI was useful in determinations of 19
      norandrosterone, boldenone, 19-noretiocholanolone, 2-methylandrosterone,
      nandrolone, 1-methyleneandrosterone, 1-methylandrosterone, 4-dihydroboldenone and
      mesterolone. The detection limits of this procedure were 5-20 ppb at a signal-to
      noise (S/N) ratio of 3.

PMID- 10209876
TI  - In vivo microdialysis/liquid chromatography/tandem mass spectrometry for the on
      line monitoring of melatonin in rat.
AB  - Liquid chromatography/tandem mass spectrometry (LC/MS/MS) has been coupled to in
      vivo microdialysis for on-line monitoring of melatonin in a freely moving rat for
      a period of 15 hours. A microdialysis probe was surgically implanted into the
      jugular vein of the rat, and deionized water was used as the perfusion medium at
      a flow rate of 1.0 microL/min. Microdialysis samples were collected in an on-line
      injector with sample injection every 30 minutes. Melatonin was dosed by
      intraperitoneal (i.p.) injection and then monitored by microdialysis/LC/MS/MS.
      The whole experiment, including the microdialysis sampling and sample injection
      into the LC/MS system, was fully automated. Metabolites of melatonin were
      identified off-line by LC/MSn experiments. Two metabolites were identified as 6
      hydroxymelatonin and cyclic 2-hydroxymelatonin, consistent with ones found
      previously in the literature.

PMID- 10209877
TI  - The rapid identification of drug metabolites using capillary liquid
      chromatography coupled to an ion trap mass spectrometer.
AB  - Capillary liquid chromatography (LC) using a 320 microns column and a flow rate
      of 10 microL/min has been coupled to an ion trap mass spectrometer using
      electrospray ionisation (ESI) to enable the rapid and effective identification of
      metabolites in urine, following oral administration of a novel human neutrophil
      elastase inhibitor, GW311616. Metabolites were identified from their mass (MS)
      spectra and tandem (MS/MS) mass spectra using minimal sample (1 microL of urine)
      and no sample pretreatment. Sensitivity assessment has shown that both molecular
      weight and structural information is obtainable on as little as 5 pg of compound,
      making the capillary LC/ion trap system as described an ideal analytical tool for
      the detection and characterisation of low level metabolites in biofluids
      (particularly when sample volume is limited). This level of detection was
      unattainable using a triple quadrupole mass spectrometer operating in full-scan
      mode, although 200 fg on column was detected using selected reaction monitoring
      target analysis.

PMID- 10209878
TI  - Efficient removal of sodium dodecyl sulfate (SDS) enhances analysis of proteins
      by SDS-polyacrylamide gel electrophoresis coupled with matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry.

PMID- 10209879
TI  - Mass balance and distribution of sludge-borne trace elements in a silt loam soil
      following long-term applications of sewage sludge.
AB  - Soil samples were collected at 15-cm increments to a depth of 75 cm from plots on
      a silt loam soil where until several years earlier and for 14 years,
      anaerobically digested sewage sludge had been annually applied by furrow
      irrigation. The study protocol consisted of four replications of 6.1 x 12.2-m
      plots with 0 (T0), 1/4-maximum (T1), 1/2-maximum (T2) and maximum (T3) sludge
      application rates randomized within blocks. When sludge applications were
      terminated, maximum sludge-treated plots had received 765 Mg ha-1 (dry weight
      equivalent) of sludge solids. Total soil concentrations of Cd, Cr, Cu, Ni, Pb and
      Zn had been significantly enhanced by all sludge application rates to a soil
      depth of 30 cm. Below the 30-cm depth, total soil Cd was increased to 75 cm,
      total Zn to 45 cm (T2 and T3 only), total Cr to 60 cm (T2 and T3 only), but total
      Cu, Pb, and Ni were not increased at depth. Despite the lack of significant
      increases in subsoil concentrations for some metals, mass balance calculations
      showed a relatively high proportion of all the above sludge-borne heavy metals to
      be unaccounted for in the soil profile for each application rate. Mass balance
      calculations of losses ranged from a high of 60% for Ni to a low of 36% for Cu
      and Pb. Similar losses were calculated from metal concentrations measured in soil
      samples taken at the time the sludge was applied. In soil surface samples (0-15
      cm) from maximum sludge-treated plots, percentages of total metal concentration
      extracted with 4.0 M HNO3 ranged from a low of 31 for Zn to a high of 75 for Cu.
      Efficiency of metal extraction by HNO3 was inconsistent, depending on the soil
      horizon and sludge treatment, so that evaluation of HNO3-extractable metals is
      not a reliable method of estimating total metal retention in the profiles. In
      soil surface samples from maximum sludge-treated plots, the percentage of total
      metal contents extracted with DTPA ranged from a low of 0.03 for Cr to a high of
      59 for Cd. The DTPA extractable levels of Cu, Ni, and Pb were higher in the
      subsoils of the sludge-treated soils, indicating that these metals had been
      redistributed from the surface layer to deeper zones in the profile of sludge
      amended soil, despite the absence of elevated total concentrations of these three
      metals in the deeper subsoil.

PMID- 10209880
TI  - Distribution of 1,4-dioxane in relation to possible sources in the water
      environment.
AB  - The distribution of 1,4-dioxane was investigated in surface and groundwater in
      relation to possible sources. Water samples from river, coastal sea, and
      groundwater were collected and examined in Kanagawa Prefecture, Japan, from 1995
      to 1998. Almost all samples were contaminated by 1,4-dioxane. On annual changes,
      the concentrations did not vary significantly in river water. However, some
      samples were still heavily polluted in groundwater. The highest correlation was
      between the concentration of 1,4-dioxane and 1,1,1-trichloroethane in the
      polluted groundwater samples. Soil and groundwater that was polluted by 1,1,1
      trichloroethane in the past is still a possible source of 1,4-dioxane. In regard
      to a survey of other sources, effluents from the combined collection treatment
      from apartment houses, river basin sewage systems, and chemical plants were
      examined. The load unit of 1,4-dioxane from the treated effluent of domestic
      wastewater was assumed to be approximately 0.25 mg/person/day. This was derived
      from commonly used household chemicals, which contained 1,4-dioxane as a by
      product. In river basin sewage systems, the concentrations in effluents varied
      significantly. High concentration inflows were probably not degraded and
      released. Although 50-60% of removal was recognized in acclimatized activated
      sludge from a chemical plant, 1,4-dioxane was easily desorbed with water from
      sludge.

PMID- 10209881
TI  - Assessment of metal content and toxicity of leachates from teapots.
AB  - Metallic teapots traditionally used in Morocco were investigated for release of
      toxic metals from the teapots and their toxicity, as determined by MetPAD, a
      bacterial toxicity test that is specific for heavy metal toxicity. Our data show
      that some teapots were non-toxic while a few others were highly toxic, as shown
      by MetPAD. Tea addition reduced somewhat heavy metal toxicity due possibly to the
      complexing ability of tea. Chemical analysis of teapot leachates showed that some
      contained zinc and copper. Teapot No. 5, which showed the highest toxicity, also
      displayed the highest Zn concentration (7.39 mg/l), confirming the toxicity data.
      Based on estimates of tea consumption in Morocco, we showed that the extra daily
      burden of Zn ranged from 1.75 to 4.2 mg/day, assuming the maximum zinc
      concentration of 7.4 mg/l, as found in our study. This represents 3.5-8% of the
      LOAEL for zinc of 50 mg/day and would not be important as compared to other
      sources zinc intake.

PMID- 10209883
TI  - [The 72nd annual meeting of the Japanese Society for Bacteriology. Tokyo, Japan.
      March 24-26, 1999. Abstracts].

PMID- 10209882
TI  - [Regional meeting of the Japanese Society of Otolaryngology. Japan. 1999.
      Abstracts].

PMID- 10209884
TI  - Hybridization of complementary strand and single-base mutated oligonucleotides
      detected with an on-line acoustic wave sensor.
AB  - The hybridization of a biotinylated 25-mer oligonucleotide probe with
      complementary, non-complementary and single-base mutated 25-mer targets at the
      liquid-solid (neutravidin-modified) interface of a thickness-shear mode acoustic
      wave device was studied. The sensor was incorporated into an on-line
      configuration capable of both variable flow and stop-flow experiments. Under
      ambient temperature conditions different signals were obtained for the
      complementary and non-complementary cases. At higher temperatures, the former
      system exhibits behaviour characteristic of the production of intermediate
      duplexes which are decomposed by the re-introduction of buffer solution. The use
      of these conditions allows the distinction of binding events involving a set of
      single-base mutated 25-mers. Different responses were obtained depending on both
      the nature of the instigated mismatch in base pairing and on the location of
      mutation.

PMID- 10209885
TI  - Trends in electrochemical biosensors.
AB  - The development of electrochemically based biosensors is discussed in the context
      of what has been learned from the successful development of glucose biosensors.
      Some future trends are discussed.

PMID- 10209886
TI  - Optimisation of a reagentless laccase electrode for the detection of the
      inhibitor azide.
AB  - Here we report on the optimisation of a reagentless enzyme sensor for the
      detection of azide based on the mediated reduction of O2 by a laccase enzyme co
      immobilised in a redox hydrogel on electrode surfaces. The sensor response is
      shown to be influenced by the enzyme loading, the electrolyte pH and ionic
      strength. The response of the sensor is stable, decreasing by only 25% over a
      sixteen-hour period. Reproducible inhibition curves for the determination of
      azide levels from cyclic voltammetric scans can be obtained by normalisation of
      the sensor response. The resulting enzyme inhibition biosensor can detect levels
      of azide as low as 2.5 microM under these conditions. Constant potential
      amperometric detection at the laccase enzyme electrode in a flow injection set-up
      yields a peak current for inhibition of the mediated reduction of O2.
      Reproducible peak currents and areas (8.0 and 6.3% RSD, respectively, for n = 11)
      are obtained for repeated injections of 100 microM azide. Reproducible response
      curves can be obtained by injection of a 25 mM azide sample and assuming that the
      peak height and peak area obtained represent 100% inhibition of the enzyme.

PMID- 10209887
TI  - Non-aqueous enzymology approach for improvement of reagentless mediator-based
      glucose biosensor.
AB  - The formation of Nafion membranes containing glucose oxidase and
      dimethylferrocene as a mediator was optimized using a previously reported non
      aqueous enzymology approach for biosensor development. Enzyme immobilization in
      Nafion membranes was carried out from water-organic mixtures with a high content
      of organic solvent. The mediator based reagentless glucose electrode was tested
      in a flow injection system. The response towards glucose addition was stable: the
      reproducibility during 50 assays exceeded 95%. The response was linear over the
      glucose concentration range 0.5-50 mM.

PMID- 10209888
TI  - Self-gelatinizable copolymer immobilized glucose biosensor based on prussian blue
      modified graphite electrode.
AB  - A novel poly(vinyl alcohol) grafting 4-vinylpyridine self-gelatinizable copolymer
      was adapted to immobilize glucose oxidase. The reduction of hydrogen peroxide
      (H2O2) was detected at a Prussian Blue (PB) modified graphite electrode. A stable
      and sensitive glucose amperometric biosensor is described. The copolymer is a
      good biocompatible polymer in which the glucose oxidase retains high activity.
      Moreover, the copolymer can adhere firmly to the inorganic PB membrane. The
      sensor showed an apparent Michaelis-Menten constant of 18 +/- 0.2 mM and a
      maximum current density of 1.14 microA cm-2 mM-1. The linear range is from 5
      microM to 4.5 mM glucose and the detection limit is 0.5 microM glucose. The
      catalytic efficiency of PB for the reduction of H2O2 is higher than that for the
      oxidation of H2O2. Glucose concentrations in serum samples from healthy persons
      and diabetic patients were determined using the sensor. The results compared well
      with those provided by the hospital using a spectroscopy method.

PMID- 10209889
TI  - Measurement of sulfite at oxide-coated copper electrodes.
AB  - The amperometric determination of sulfite was performed using copper electrodes
      in alkaline media. A mechanism for the oxidation of sulfite at these electrodes
      is suggested, based on the formation of superficial CuO(.OH), which acted as an
      electron transfer mediator to the analyte. At 0.5 V versus SCE in 1 M NaOH,
      sulfite could be calibrated at a sensitivity of 0.2 A l mol-1 cm-2, with a
      response time for the steady state of 30 s. The limit of detection (three times
      the signal-to-noise ratio) was 2.5 x 10(-6) M and the response was linear up to 5
      x 10(-4) M (r2 = 0.9996, n = 15). The standard deviation (n = 10) at 1 x 10(-5)
      and 1 x 10(-4) M was 3.27 x 10(-7) A cm-2 (mean = 3.62 x 10(-6) A cm-2) and 1.07
      x 10(-13) A cm-2 (mean = 2.25 x 10(-5) A cm-2), respectively.

PMID- 10209890
TI  - Chemometric analysis of high performance liquid chromatography-diode array
      detection-electrospray mass spectrometry of 2- and 3-hydroxypyridine.
AB  - Triply coupled high performance liquid chromatography using diode array detection
      and positive ion electrospray mass spectrometry of 2- and 3-hydroxypyridine is
      presented. Considerations of the physical method for coupling the two detectors,
      the influence of pH on retention times, the cone voltage of the mass spectrometer
      and the linear concentration ranges are described. Data from both detectors are
      aligned and interpolated. The analyte mass spectra are reduced to 20 significant
      masses. Principal components plots on the raw, normalised and standardised data,
      derivatives to determine composition 1 regions, deconvolution and procrustes
      analysis to compare data from both detectors are discussed. Common trends in both
      mass spectral and diode array chromatograms are interpreted. This paper
      represents a new approach to common processing of chromatographic data from two
      detectors.

PMID- 10209891
TI  - Near-infrared mass median particle size determination of lactose monohydrate,
      evaluating several chemometric approaches.
AB  - The influence of particle size on near-infra red (NIR) spectra is typically
      considered a 'nuisance factor' which many scatter correction methods attempt to
      eliminate, e.g., multiplicative scatter correction. However, particle size is a
      key issue in the formulation of many pharmaceutical products and has a profound
      effect on the behaviour of both raw materials and drug substances during
      formulation. NIR has already been demonstrated as a potential alternative
      particle sizing technique to current accepted methodology. This investigation
      assessed several chemometric approaches that model this information, using
      lactose monohydrate as the raw material. A variety of modelling techniques were
      applied to both zero order and second derivative spectra namely multiple linear
      regression, partial least squares, principal component regression and artificial
      neural networks. One further data transformation evaluated was polar coordinates,
      although no statistical data were generated. Typically, cross-validation root
      mean square errors of calibration and cross-validation root mean square errors of
      prediction of approximately 5 microns were calculated for all of the modelling
      techniques. These values are comparable to those associated with the reference
      technique (laser diffractometry). Correlation coefficients of approximately 0.98
      for all techniques were also calculated. The predictive abilities for models
      generated using second derivative spectra were found to be comparable to those
      obtained using zero order spectra.

PMID- 10209892
TI  - Trilinear PARAFAC decomposition of synchronous fluorescence spectra of mixtures
      of the major metabolites of acetylsalicylic acid.
AB  - Mixtures of the three major metabolites of acetylsalicylic acid (salicylic,
      gentisic and salicyluric acid) were analyzed by synchronous molecular
      fluorescence spectroscopy. Three-way data matrices were generated by acquisition
      of spectra as a function of the pH (between 2 and 11) and of different relative
      concentrations of the three components. The PARAFAC trilinear model, without
      restrictions and using one factor per metabolite, was used in the data analysis.
      A full decomposition of the data matrices into the spectra, concentration and pH
      profiles was obtained. This result shows that molecular fluorescence spectroscopy
      can be used for the development of robust analytical methods for the simultaneous
      determination of the three major metabolites of acetylsalicylic acid in complex
      background samples.

PMID- 10209893
TI  - Determination of hexamethylene-based isocyanates in spray-painting operations.
      Part 1. Evaluation of a polyurethane foam sponge sampler.
AB  - A polyurethane foam (PUF) sponge was mounted in a cassette sampler and evaluated
      as a sorbent for the collection of hexamethylene diisocyanate (HDI) monomer and
      HDI-based oligomers. Recovery studies indicated 112 +/- 34% average recovery of
      HDI monomer and 92 +/- 9% and 97 +/- 25% average recovery of HDI-based oligomers
      when using impregnated PUF sponges. The PUF sponge was also evaluated during
      actual spray-painting operations. In a series of side-by-side sampling events, an
      impinger filled with 1-(2-methoxyphenyl)piperazine (MOP) in toluene was compared
      directly with a cassette sampler containing a PUF sponge impregnated with MOP or
      1-(9-anthracenylmethyl)piperazine (MAP) in dimethyl sulfoxide (DMSO). For the
      analysis of HDI-based oligomer, there is no significant difference (p < 0.05, n =
      7) in the air concentration when sampling with either the PUF sponge cassette or
      the impinger. The results are significant because they indicate that a PUF
      sponge, which is more convenient than an impinger, may be used for the collection
      of HDI-based oligomer generated during spray-painting operations.

PMID- 10209894
TI  - Quantification of total chromium and hexavalent chromium in UHT milk by ETAAS.
AB  - Procedures for the quantification of total chromium and hexavalent chromium in
      UHT milk samples are presented. Total chromium was determined directly in milk
      with the addition of a surfactant and a mixture of Pd and Mg as a chemical
      modifier. For the selective separation of hexavalent chromium, the sample pre
      treatment consisted in precipitation of proteins and elution of the supernatant
      through a Chromabond NH2 column. The metal was eluted with nitric acid. Both
      total chromium and hexavalent chromium were evaluated by atomic absorption
      spectrometry with electrothermal atomization using the same instrumental
      conditions. The detection limits were 0.2 and 0.15 microgram l-1 for total
      chromium and hexavalent chromium, respectively. The linearity ranges under the
      optimized conditions were 0.2-20 and 0.15-50 micrograms l-1. For total chromium
      the precision was 4.9 and 5.7% for the analytical and the over-all procedure,
      respectively, and for hexavalent chromium 4.3 and 4.9%, respectively. The
      validation of both procedures was performed by the standard additions method and
      the recoveries were higher than 93% in all cases. For total chromium, a certified
      reference material was also used to validate the methodology. The methods were
      applied to the determination of total chromium and hexavalent chromium in 60 UHT
      milk samples.

PMID- 10209895
TI  - Determination of cyanide by a flow injection analysis-atomic absorption
      spectrometric method.
AB  - A new flow injection analysis (FIA) procedure is proposed for the indirect atomic
      absorption spectrometric determination of cyanide. The FIA manifold is based on
      the insertion of the sample into a distilled water carrier, then the sample flows
      through a solid-phase reactor filled with silver iodide entrapped in polymeric
      resin beads. The calibration graph is linear over the range 0.2-6.0 mg l-1 of
      cyanide (correlation coefficient 0.9974), the detection limit is 0.1 mg l-1, the
      sample throughput is 193 h-1 and the RSD is 0.8%. The method is simple, quick and
      more selective than other published FIA procedures. The reproducibility obtained
      by using different solid-phase reactors and solutions is in the range 2.2-3.1%
      (RSD). The method was applied to the determination of cyanide in commercial
      samples such as pharmaceutical formulations and industrial electrolytic baths.

PMID- 10209896
TI  - Determination of trace level gamma-aminobutyric acid using an improved OPA pre
      column derivatization and on-column preconcentration capillary liquid
      chromatography with electrochemical detection.
AB  - An improved pre-column derivatization with o-phthalaldehyde/tert-butylthiol and
      on-column preconcentration are used with packed capillary liquid chromatography
      and electrochemical detection to obtain low concentration detection limits for
      gamma-aminobutyric acid (GABA). Using derivatization procedures from the
      literature, it was found that the detection limits for GABA were 380 amol in 50
      microns i.d. packed capillaries, which is over 10-fold worse than the detection
      limit possible with the instrumentation. The higher detection limit was directly
      the result of electroactive interferences generated by the derivatization
      chemistry. Derivatization was improved by scavenging excess reagents with excess
      amine and iodoacetamide. With these improvements, the interfering peaks were
      eliminated and the detection limit was improved to 50 amol. With injection
      volumes of 0.5 microL, under conditions that permitted on-column
      preconcentration, the concentration detection limit, that is the concentration at
      which analytes could be derivatized and detected, was 100 pM. The technique was
      applied to determination of GABA release from islets of Langerhans.

PMID- 10209897
TI  - Characterization of horse kidney metallothionein isoforms by electrospray MS and
      reversed-phase HPLC-electrospray MS.
AB  - Pneumatically assisted electrospray mass spectrometry (ESMS) in the direct mode
      and as a chromatographic detection technique was developed for the
      characterization of horse kidney metallothionein isoforms. Direct analysis in an
      acidic medium showed the presence of three major and five minor isoforms, the
      molecular masses of which were determined. The presence of the major isoforms
      (two of which matched the molecular masses calculated according to the published
      sequences) was confirmed by complexation with Cd at pH 4.0 and the determination
      of the stoichiometry of the complexes formed. Reversed-phase chromatography of
      Cd7-MT complexes (pH 6.0) gave two signals corresponding to the MT-1A and MT-1B
      isoforms. A post-column acidification procedure was developed to eliminate the
      possibility of artefacts associated with the formation of mixed-metal (Cd, Zn)
      complexes during chromatography in neutral media, and to improve the accuracy of
      the determination of the molecular mass of MT isoforms.

PMID- 10209898
TI  - Chiral determination of amphetamine and related compounds using chloroformates
      for derivatization and high-performance liquid chromatography.
AB  - The enantiomeric determination of amphetamine and various amphetamine-type
      compounds by liquid chromatography after chiral derivatization with 9
      fluorenylmethyl chloroformate-L-proline (FMOC-L-Pro) is reported. The results
      obtained were compared with those achieved after achiral derivatization with 9
      fluorenylmethyl chloroformate and subsequent separation of the derivatives on a
      beta-cyclodextrin chiral stationary phase. Conditions for the derivatization of
      amphetamines with FMOC-L-Pro were investigated, including the effect of the
      derivatization reagent concentration, pH and reaction time, using amphetamine,
      ephedrine and pseudoephedrine as model compounds. On the basis of these studies,
      possible conditions for the determination of each amphetamine are indicated. To
      demonstrate the utility of the proposed procedures, data on linearity,
      repeatability and sensitivity are given. Results of the determination of
      ephedrine enantiomers in different pharmaceutical samples are also presented.

PMID- 10209899
TI  - HPLC determination of residues of spectinomycin in various tissue types from
      husbandry animals.
AB  - An HPLC method was developed for the determination of bacteriostatic
      aminocyclitol spectinomycin (SP) in animal tissue products. These products
      included chicken eggs and edible fat, kidney, liver, muscle tissues from calf,
      poultry, pig and sheep. Residues of SP were extracted from homogenized tissue and
      egg-derived material with 25 mM citrate of pH 4.0, trichloroacetic acid and
      dichloromethane. The extract was purified and concentrated over a carboxylic acid
      bonded solid-phase extraction (SPE) column. The SPE-eluate was analysed by cation
      exchange HPLC involving a two-column switching system, post-column derivatization
      and fluorescence detection. Spectinomycin could be successfully determined at
      levels of 0.05 mg kg-1 and higher. Recoveries from spiked tissue material and
      from spiked egg material were in excess of 74% and did not show a concentration
      or tissue-type dependence. Precision of the elution position and signal response
      was better than 2%. Matrix effects and interference from lincomycin were less
      than 7 and 2%, respectively, on the signal response. Spectinomycin was shown to
      be stable at -20 degrees C in combined egg yolk and white over a test period of
      12 weeks and in calf and sheep muscle tissue over a test period of 10 days. SP
      was, however, not stable at this temperature over a period of 12 months in
      chicken muscle tissue. Incurred SP residues were successfully determined in
      kidney and muscle tissue at the injection site of pigs administered with two
      doses of 15 mg kg-1 body weight SP with an intermittent withdrawal period of 15
      days. Kidney showed higher concentrations and more persistent residues of SP than
      muscle tissue at the injection site.

PMID- 10209900
TI  - Rapid determination of polycyclic aromatic hydrocarbons in tea infusion samples
      by high-performance liquid chromatography and fluorimetric detection based on
      solid-phase extraction.
AB  - This paper describes a method for the determination of PAHs in black, green and
      decaffeinated tea infusion samples. The method is based on the solid phase
      extraction of the PAHs using Sep-Pak vac tC-18 cartridges. The PAHs are then
      eluted from the cartridges with dichloromethane. Quantification and detection are
      carried out by HPLC with a fluorimetric detector using a program of excitation
      and emission wavelength pairs. Recoveries at concentration levels in the range
      190-1790 ng l-1 were higher than 65% for all PAHs except dibenz[a,h]anthracene,
      for which it was around 54%. The mean content of PAHs was in the range 28.7-112
      ng l-1 in the tea infusions, with relative standard deviations between 2 and 18%
      (n = 4).

PMID- 10209901
TI  - Determination of geosmin and 2-methylisoborneol in water using solid-phase
      microextraction and gas chromatography-chemical ionisation/electron impact
      ionisation-ion-trap mass spectrometry.
AB  - A method for the determination of geosmin and 2-methylisoborneol (MIB) in water
      by solid-phase microextraction (SPME) is presented. Various SPME fibre
      chemistries have been compared for their efficiency in extracting MIB from water.
      Extraction conditions including the extraction time and temperature have been
      optimised. A 30 ml water sample is extracted for 20 min at 60 degrees C using a
      divinylbenzene fibre, and the extract analysed by gas chromatography with ion
      trap mass spectrometry detection. d5-Geosmin and d3-MIB are added as internal
      standards to compensate for any variability in the SPME process which is not
      carried out to equilibrium. Chemical ionisation, using acetonitrile as the
      reagent gas, was found to give superior sensitivity to electron impact ionisation
      (EI) for the detection of MIB. EI was used as the ionisation mode for detection
      of geosmin. The method shows good linearity over the concentration range 5-40 ng
      l-1 and gives detection limits of 1 ng l-1 for both geosmin and MIB. Recovery (93
      110%) and precision (3-12%) over this concentration range, for both raw and
      treated drinking waters, are comparable to currently employed methods such as
      closed-loop stripping analysis (CLSA). The method offers the advantage of being
      simple to use, with much shorter analysis times in comparison to CLSA.

PMID- 10209902
TI  - Protein adsorption to organosiloxane surfaces studied by acoustic wave sensor.
AB  - Surfaces of the two organosiloxanes, polymercaptopropylmethylsiloxane and
      octaphenylcyclotetrasiloxane, were prepared on the gold electrodes of thickness
      shear mode acoustic wave sensors. Compounds containing the siloxane bond are
      important in the fabrication of medical implants. The flow-through adsorption of
      the proteins: human serum albumin, alpha-chymotripsinogen A, cytochrome c,
      fibrinogen, hemoglobin, immunoglobulin G and apo-transferrin to the two siloxane
      surfaces and a gold electrode were detected by acoustic network analysis. With
      the exception of minor wash-off by buffer flow, the adsorption of all proteins to
      the three surfaces is irreversible. Differences observed for the magnitudes of
      adsorption for the various cases are ascribed to the role played by molecular
      interactions at the liquid/solid interface. The results confirm that changes in
      series resonant frequencies caused by macromolecular adsorption differ
      significantly from the widely accepted "mass based" model usually employed to
      characterize the response of this type of acoustic wave device.

PMID- 10209903
TI  - Indirect laser photoacoustic detection for trace samples on membranes.
AB  - An indirect laser photoacoustic technique is described. The basic principle, the
      experimental set-up and the influencing factors are discussed in detail. This
      method was used to quantify phenylamine, arginine and methylene blue on
      membranes. The linear ranges of the calibration curve are up to two orders of
      magnitude. With 1 microliter of sample solution, the detection limits are 0.25,
      1.52 and 0.14 pmol for phenylamine, arginine and methylene blue, respectively.

PMID- 10209904
TI  - [Computer-assisted analysis of sperm morphology in veterinary medicine].
AB  - The evaluation of spermatozoal morphology is an essential step to determine the
      fertility potential in male individuals. The method of computer-assisted
      morphometry provides an efficient tool to evaluate objectively morphological
      anomalies of the sperm head. This review describes the development and current
      status of morphometry systems and addresses the various problems associated with
      this method in veterinary medicine. Although there are some unanswered questions,
      a number of interesting results have been obtained. In all species investigated
      an individual influence on sperm head dimensions could be demonstrated. In the
      bull the extent of variability rather than absolute morphometric data is related
      to individual fertility. The method of computer-assisted morphometry will also
      help to develop well defined criteria for subjective evaluation of sperm
      morphology. Further research has to be directed towards the evaluation of the
      sperm mid-piece. The ultimate goal is the automatic determination of spermatozoal
      morphology.

PMID- 10209905
TI  - [Sudden deaths in taking blood samples from fattening swine herds-- experiences
      from practice].
AB  - Experiences in a large-scale blood sampling was the cause for reflections about
      the reason of sudden deaths of pigs. The one-sided breeding of pigs in order to
      get a high lean meat content, the ability to grow rapidly and to put on weight
      causes susceptibility to exertional myopathy. In addition, in modern housing
      systems pigs grow up in an environment without any stimulus, which results in
      emotional stress, if the pigs get suddenly in a close contact to man. Therefore a
      routinely operation such as taking blood causes an abnormal acceleration of
      glycolysis and the development of lactacidosis and sometimes a circulatory
      insufficiency up to sudden death. The metabolic acidosis, which is of breeding
      origin and arises from stress, often is strengthened by pneumonia in fattening
      herds caused by faulty husbandry, high animal concentration, stall climate and a
      high risk of infection. Because of this the metabolic acidosis cannot be
      compensated for by respiration. The high number of sudden deaths caused by
      lactacidosis and cardiac shock (fattening period: 1-12%, transport to slaughter:
      0.4%, and 0.45% in the own investigation into blood sample taking from fattening
      pigs [weight: 80-110 kg]) emphasizes the problem. The exertional myopathy is not
      only characterized by sudden death but also by poor meat quality due to PSE. From
      the point of view of animal welfare as well as from the point of view of the
      consumer it is desirable to change the aim of breeding, especially by reducing
      lean meat content as well as to improve the type of husbandry.

PMID- 10209906
TI  - [Examination of systemic tumor necrosis factor activity under physiologic and
      pathophysiologic conditions].
AB  - Tumor necrosis factor (TNF) activity in the circulation of several animal species
      was determined by a bioassay, using the murine cell line L929. In healthy adult
      cattle, horses, pigs and dogs, species specific differences of systemic TNF
      activity were visible. In cattle, TNF activity in the circulation increased
      during growing up from calf to adult animal. In cattle suffering from various
      diseases, unchanged, elevated, but also reduced systemic TNF activity have proved
      to possess clinical relevance. Low systemic TNF activity frequently occurs during
      lethal inflammatory diseases and may be an indicator of generalized monozyte
      paralysis.

PMID- 10209907
TI  - [Listeriosis in the European brown hare in northern Germany].
AB  - During the years 1988-1997 listeriosis was detected in nine (2.4%) of 373
      perished hares, in one of these cases calicivirus was additionally found. The
      listeriosis occurred sporadically. Granulomatous hepatosplenomegaly was the main
      lesion observed. Pregnancy is an important predisposing factor for the outbreak
      of listeriosis: six of the nine cases were hares post abortum or with retention
      of macerated foetuses in utero.--Six Listeria strains were serotyped and all
      belonged to serovar 1/2a.

PMID- 10209908
TI  - [Coupling of immunomagnetic separation and polymerase chain reaction for the
      rapid detection of salmonellae in minced meat and chicken giblets].
AB  - Coupling of immunomagnetic separation and polymerase chain reaction was used
      after preenrichment for the rapid detection of salmonellae in minced meat and
      chicken giblets. The primers used are specific to the origin of DNA replication
      (oriC) on the Salmonella chromosome and produce a 163 bp DNA fragment. The method
      allowed a screening of Salmonella free samples within 24 hours. It detected 5
      serovars when inoculated in minced meat at a contamination level of 1 to 4 cfu/g.
      Compared with the method L 00.00-20 of the Official Collection of Methods of
      Analysis according to section 35 of the German Law on Food and Commodities it
      showed a sensitivity of 94% and a specificity of 87.5% for the examination of
      chicken giblets (n = 45) and a specificity of 100% for the examination of minced
      meat (n = 63).

PMID- 10209909
TI  - [Fungal flora in chicken stalls and its etiopathogenic importance for humans and
      animals].
AB  - In order to find out the mycoflora prevailing in chicken pens, and to appreciate
      the health hazards for employees (incl. veterinarians) and animals, twenty litter
      samples and 6 sedimented dust trials were analysed mycologically. The following
      results were found: Bedding and dust samples all contained between 3.57 and 1.30
      x 10(7) c.f.u./g DW. The commonest fungus is A. fumigatus with 3.41 x 10(4) -
      1.30 x 10(7) c.f.u./g DW in bedding and 2.70 x 10(5) - 3.30 x 10(6) c.f.u./g DW
      in sedimented dust. In addition, the following fungal spp. were detected (in
      c.f.u./g DW): Scopulariopsis brevicaulis (3.57 x 10(3) - 6.50 x 10(7)),
      Pseudallescheria boydii (2.70 x 10(6)), A. flavus group (up to 8.41 x 10(5)), A.
      clavatus (6.00 x 10(5)), Candida albicans (4.88 x 10(5)), Alternaria spp. (4.49 x
      10(5)), Penicillium spp. (up to 1.06 x 10(5)), A. terreus (8.47 x 10(4)), A.
      versicolor group (up to 8.44 x 10(4)), A. niger (5.93 x 10(4)), Aureobasidium sp.
      (3.96 x 10(3)), Mucor circinelloides (3.42 x 10(3)), Phialophora sp. (1.30 x
      10(3)), C. pseudoiropicalis (4.04 x 10(2)), A. nidulans (3.90 x 10(2)),
      Acremonium sp. (3.55 x 10(2)), M. racemosus (1.19 x 10(2)). Negligible was the
      detected level of Chrysosporium pannorum (84.10), Rhizomucor pusillus (81.00),
      Beauveria alba (59.60), C. tropicalis (40.40), Trichoderma sp. (4.70), A.
      flavipes (4.38). Dermatophytes were not found. The fungal spectrum was broader in
      the dust than in litter samples.

PMID- 10209910
TI  - VTEC O157 phage type 21/28 infection in North Cumbria: update.

PMID- 10209911
TI  - Salmonella java phage type Dundee--rise in cases: update.

PMID- 10209912
TI  - Perspectives on personal protective equipment.

PMID- 10209913
TI  - Accidental exposures to blood and other body fluids in a large academic medical
      center.
AB  - Healthcare workers' and students' exposures to blood-borne pathogens during a 1
      year period (1997) at a large university academic medical center were analyzed.
      The university health manages the Blood-Borne Pathogen Post-Exposure Control
      Program at the university and treats all reported exposures of students, faculty,
      and staff. Comparative exposure rates for all categories of healthcare workers,
      the work site where injuries occurred, and the circumstances involved in 298
      exposure incidents are outlined. A standardized postexposure prophylaxis protocol
      provides for definition of the health status of all known source patients and
      assessment of the potential need for treatment of the exposed clinician.
      Implications of the study for focusing on improvements in training healthcare
      workers in proper procedures and the use of personal protective equipment in
      dealing with blood-borne pathogens are discussed.

PMID- 10209914
TI  - Exposure of medical students to body fluids.
AB  - Three hundred forty-two students at 3 Florida medical schools were surveyed
      concerning occupational exposures to blood and body fluids during their 3rd-year
      clerkship. The 16-item questionnaire was anonymously returned by 150 students,
      and differences among groups were assessed at p < .05. Most of the students
      complied with universal precautions guidelines (UVPG); 62 reported 101 exposures,
      including 9 with HIV-positive blood and body fluids. Most of the exposed students
      knew about the guidelines but regarded the incidents as irrelevant to their
      safety or supervision training. Noncompliant students reported significantly more
      exposures than compliant students. Time constraints, inconvenience of using
      gloves during procedures, and belief that patients were at low HIV risk
      discouraged adherence to the guidelines. Common practices following exposure were
      "no action" or "washed area only" without medical follow-up. Medical students'
      UVPG adherence should be increased by workload modification, user-friendly safety
      products, and supervised practice training in clinical exposure settings.

PMID- 10209915
TI  - What date/acquaintance rape victims tell others: a study of college student
      recipients of disclosure.
AB  - The authors surveyed 828 college students and found that approximately one third
      (n = 282) of the respondents reported that one or more women had told them that
      they had been raped by their dates or acquaintances. The 282 respondents who knew
      1 or more victims of date/acquaintance rape reported on a total of 396 victims.
      The number of victims identified by respondents ranged from 1 to 3 or more (1 =
      73%; 2 = 19%, 3 = 5%, > or = 4 = 3%). Reactions to disclosure offered by these
      respondents were generally supportive of the victim. The respondents' reactions
      suggested that there is a continuing need to educate students about the incidence
      and risks associated with date/acquaintance rape and the possibility of
      disclosure, particularly by friends or dating partners, and brought out some
      possible helpful and some counterproductive reactions to such disclosures.

PMID- 10209916
TI  - Knowledge of cervical cancer screening among women attending a university health
      center.
AB  - One hundred fifty-four female students completed a questionnaire regarding the
      Pap test and cervical cancer screening during routine yearly examination at a
      university health center. Ninety percent knew that a Pap test screened for
      precancerous and cancerous lesions of the cervix. More than half of the students,
      however, thought that the test also screened for other forms of gynecologic
      cancer and for a variety of sexually transmitted diseases. Approximately half of
      the respondents were unfamiliar with proper preparation for the test (e.g.,
      avoiding sexual intercourse and intravaginal contraceptive application) and the
      majority did not know about specific risk factors for cervical cancer. These
      findings indicate a need for improved health education efforts regarding the risk
      factors for cervical disease and the role and importance of Pap smears.

PMID- 10209917
TI  - Testing an explanatory model of the development of depressive symptoms in young
      women during a life transition.
AB  - Factors to explain the rising incidence of depressive symptoms among young women
      making the transition from home to university life were investigated. A path
      analysis of data from 213 18- and 19-year-old women entering a large university
      indicated that negative life events, interpersonally derived social support, self
      esteem, and depressive symptoms were significantly related. Negative life events
      that affected the women's self-esteem (drawn from the women's performance in
      interpersonal relationships) were most strongly associated with depressive
      symptoms, and self-esteem derived through efficacy (i.e., taking control and
      acting assertively) was not associated with negative events. The women in the
      sample appeared to derive efficacy self-esteem from relationships. An analysis of
      the data supported developing interventions to improve interpersonal
      relationships rather than focusing on competence in gaining access to resources.

PMID- 10209918
TI  - Using formative research to conceptualize and develop a marketing plan for
      student health services.
AB  - Conceptualization and development of a health services awareness campaign at the
      University of Kentucky followed the steps in a communication process called
      formative research. Preproduction surveys and subsequent testing of possible
      initiatives led to creation of a popular video featuring the university mascot
      that is being used in new-student orientation.

PMID- 10209919
TI  - Treatments of generalized pustular psoriasis: a multicenter study in Japan.
AB  - This study analyzed data from treatments of 385 cases of generalized pustular
      psoriasis (GPP) from 325 hospitals in Japan. Retinoid treatment was effective in
      84.1% of patients, methotrexate in 76.2%, cyclosporine in 71.2%, oral PUVA
      therapy in 45.7%, and tonsillectomy in 16.7%. Short-term therapy with systemic
      corticosteroid for GPP during only the phase with severe systemic clinical
      findings may be also effective (75.4%). However, these treatments for GPP each
      differed in clinical effects, prognosis, and side effects. These findings may be
      useful in creating guidelines for treatment of generalized pustular psoriasis.
      Further studies based on these specific clinical effects are necessary.

PMID- 10209920
TI  - Linear IgA bullous dermatosis associated with ulcerative colitis.
AB  - A 41-year-old woman developed skin vesicles one week before examination. She had
      been suffering from ulcerative colitis since the age of 30. Histologic
      examination of a vesicle showed a subepidermal bulla accompanied by mononuclear
      leukocyte infiltration intermingled with eosinophils and neutrophils.
      Eosinophilia was also noted. Direct immunofluorescent test revealed linear
      deposits of IgA in the basement membrane zone.

PMID- 10209921
TI  - Pemphigus vulgaris preceded by herpetiform-like skin lesions with negative
      immunofluorescence findings.
AB  - We report a case of pemphigus vulgaris in a 63-year-old woman. At the first
      onset, she developed herpetiform-like skin lesions. Their histology showed
      eosinophilic spongiosis and intraepidermal blister formation with an infiltrate
      of eosinophils. Both direct and indirect immunofluorescence studies were
      negative. She remained in remission for 6 years. At the second onset, she
      developed bullous skin lesions; histological examination disclosed suprabasal
      acantholysis and infiltration of eosinophils. Direct immunofluorescence revealed
      IgG and C3 deposits at the cell surface, predominantly in the lower epidermis.
      Indirect immunofluorescence using normal human skin as a substrate demonstrated
      anti-cell surface IgG antibodies at a titer of 1:160. Immunoblot analysis showed
      that the patient's serum reacted only with a 130 kD protein. This case indicates
      that pemphigus vulgaris can follow herpetiform-like skin lesions with negative
      immunofluorescence findings after a long remission time.

PMID- 10209922
TI  - A case of pediatric Behcet's disease with intestinal involvement.
AB  - We report a 6-year-old girl with recurrent oral aphthae, genital and perianal
      ulcers, and folliculitis-like erythema followed by intestinal symptoms. No ocular
      lesions were found. Her ailment was diagnosed as incomplete Behcet's disease with
      intestinal involvement. According to the literature, pediatric Behcet's disease
      is characterized by a low incidence of ocular lesions and a high incidence of
      intestinal involvement, as exhibited in this case. As intestinal lesions in
      pediatric Behcet's disease are often life-threatening, a barium enema must be
      given to exclude the possibility of intestinal involvement when pediatric
      patients with Behcet's disease complain of abdominal pain.

PMID- 10209923
TI  - Mucha-Habermann disease-like eruptions due to Tegafur.
AB  - The first case of Mucha-Habermann disease-like drug eruptions due to Tegafur is
      reported. A 59-year-old man noticed various skin lesions after he had taken 300
      mg of Tegafur daily for about 200 days. The patient had papulonecrotic eruptions
      on his trunk and extremities. The histology from a papular lesion revealed
      epidermal necrosis surrounded by spongiosis, perivascular inflammatory
      infiltrations composed of lymphocytes and erythrocytes, and endothelial swelling.
      The etiology of Mucha-Habermann disease is not known, but an immune mechanism may
      be supported by our case.

PMID- 10209925
TI  - Cutaneous mucormycosis.
AB  - The patient, a 59-year-old male, had been diagnosed as having alcoholic
      hepatopathy 20 years previously. He noticed localized swelling on his left leg
      after fishing in a river. The patient was diagnosed as having cutaneous
      mucormycosis upon histological and mycological examination of the skin. Gradual
      improvement of the symptoms was noted four weeks after administration of
      itraconazole and fruconazole; these were discontinued after five months.

PMID- 10209924
TI  - Detection of human papilloma virus type 58 in a case of a perianal Bowen's
      disease coexistent with adult T-cell leukemia.
AB  - A case of Bowen's disease (BD) that appeared in the perianal region of a 65-year
      old Japanese woman coexistent with chronic adult T cell leukemia (ATL) is
      described. Histopathological findings revealed that irregularly arranged tumor
      cells with atypical nuclei throughout the epidermis, which itself disclosed
      hyperkeratosis, dyskeratotic cells, and clumping cells. Positive staining for HPV
      antigens was immunohistochemically seen in several nuclei of the tumor cells.
      Electron microscopic study of the tumor tissue disclosed virus particles of about
      50 nm in diameter form the squamous cells. A positive band at 256 bp was obtained
      by PCR using HPV-L1 primer. The amplified DNA by L1 primer completely
      corresponded to that of HPV-58.

PMID- 10209926
TI  - A case of multiple sebaceous epithelioma: analysis of microsatellite instability.
AB  - Sebaceous gland tumor is a rare disease that is a sign of Muir-Torre syndrome, an
      autosomal, dominantly inherited genodermatosis characterized by the presence of
      at least one sebaceous gland tumor and a minimum of one internal malignancy.
      Recent studies have indicated that defective DNA mismatch repair occurs in Muir
      Torre syndrome. Cutaneous lesions may occur before diagnosis of the internal
      cancer. We describe a 64-year-old male patient with multiple sebaceous
      epitheliomas with no evident internal malignancy. Microsatellite instability,
      determined by examining dinucleotide CA repeats at the microsatellite loci, was
      observed in DNA from one sebaceous epithelioma but not from the other two
      sebaceous epitheliomas or from one basal cell epithelioma with sebaceous
      differentiation, suggesting that this condition is unlikely to be due to germ
      line mutation of mismatch repair genes.

PMID- 10209927
TI  - Osteo-nevus of Nanta: a case report and review of the Japanese literature.
AB  - We reported a 58-year-old Japanese male with osteo-nevus of Nanta on his right
      cheek. Histological examination revealed nests of nevus cells throughout the
      entire dermis. Just beneath the nevus in the lower dermis, several basophilic
      oval-shaped membranous structures were positive with Kossa stain. No inflammatory
      infiltrate or foreign-body granuloma were seen. We reviewed 28 cases of osteo
      nevus of Nanta reported in the Japanese literature and discussed the pathogenesis
      of ossification in the lesions of nevus cell nevi.

PMID- 10209928
TI  - Solitary cellular schwannoma (neurilemmoma) showing malignant changes: evaluation
      through magnetic resonance imaging (M.R.I.), surgical intervention, and
      histopathology.
AB  - Schwannoma (neurilemmoma) are common benign tumors arising from the peripheral
      nerve sheath. Malignant transformation is uncommon. A unique case showing such a
      transformation is reported highlighting the roles of magnetic resonance imaging,
      surgical intervention, and histopathology. The case was thoroughly investigated
      by learning the details of the sequence of events leading to the current status.
      The evaluation was made through magnetic resonance imaging. In addition, computed
      tomography and conventional radiography were used to locate any foci of
      calcification. Subsequently, the tumor's gross and microscopic morphology was
      defined by surgical intervention and histopathology. Malignant schwannoma of the
      left leg occupying the entire calf is extremely uncommon. Only ten cases have
      been reported thus far, including the current one from the Indian subcontinent.
      Malignant transformation in a schwannoma differs significantly from malignant
      nerve sheath tumors (erroneously called malignant schwannomas). An endeavour has
      been made to differentiate malignant transformation in schwannoma from other
      malignant peripheral nerve sheath tumors. An innovation in this direction is
      magnetic resonance imaging. This investigate procedure is imperative in such
      situations, along with surgery and histopathology, which may also help in
      classifying the condition.

PMID- 10209930
TI  - Allopurinol induced transitory giant fixed drug eruption: an atypical expression.

PMID- 10209929
TI  - Insect bite as possible cause of eosinophilic pustular dermatosis.

PMID- 10209931
TI  - Factors affecting QOL of the home-bound elderly disabled.
AB  - The purpose of this study was to clarify the factors affecting the quality of
      life (QOL) of the elderly home-bound patients. Data were collected from 56
      chronically disabled elderly persons (mean age of 76.7 years) who needed a long
      term home-based care. They were assessed on QOL, range of activity, functional
      capacity, and capacity of family care functioning as well as socio-economic
      condition. The QOL was evaluated by using Philadelphia Geriatric Center Morale
      Scale (PGC Morale Scale). The activities of daily living (ADL) and handicaps were
      evaluated by the Barthel index and the ESCROW profile, respectively. The capacity
      of family care functioning was also recorded according to the "Family Care Scale"
      developed by Hamamura. As a result, there was a significant difference between
      PGC Morale Scale score and Barthel index score (P < 0.05), and we found a
      negative correlation between PGC Morale Scale score and ESCROW score (P < 0.05).
      It was also revealed that the factors affecting the QOL of the home-bound elderly
      disabled were determined by the motivation, functional capacity, and capacity of
      family care functioning (P < 0.05). These results suggest that in order to
      improve their QOL, ADL must be improved, therefore, rehabilitation should be
      continued to maintain their function after discharging from hospitals and that we
      should take these factors into consideration, such as living environments and
      social conditions of the family care. The results also indicate how the patient's
      independence in the daily life influences social and economic status, and
      consequently it affects the quality of life.

PMID- 10209932
TI  - Efficacy of applied cardiovascular surgery techniques for extended resection in
      hepato-biliary-pancreatic malignancies.
AB  - The application of extracorporeal circulation (ECC) and vascular surgery
      techniques provide the possibility to resect severely advanced hepato-biliary
      pancreatic (HBP) malignancies that had been adjudged unresectable hitherto. In
      this paper, recent two successful cases are reported for the purpose of
      indicating the efficacy of ECC and vascular surgery techniques in HBP surgery.
      Two patients had a cholangiocellular carcinoma and a carcinoma of the pancreatic
      head, those metastatic lymph nodes invaded to the portal veins and the hepatic
      arteries. These tumors could be resected en bloc with these Glissonian vessels
      using a centrifugal pump through veno-venous bypass. Reconstruction of these
      portal veins was performed with autologous external iliac vein graft.
      Postoperative angiographies showed no anastomotic leakage or occlusion on
      vascular anastomotic sites in both cases, and they have gone on uneventful
      postoperative courses. Application of cardiovascular techniques in the field of
      HBP surgery might expand surgical indication for advanced malignancies.

PMID- 10209933
TI  - A case of intraductal papilloma of breast in advanced age.
AB  - Breast tumors have their various biological characteristics as to advanced age of
      patients. Intraductal papilloma is a benign tumor of the breast which is known to
      occur in the premenopausal young females. Tumors of the breast in the senile
      females are found mainly to be breast cancers. No any cases of intraductal
      papilloma over 80-years were reported in Japan to date. We have recognized
      mammary tumors in old aged patients to be cancers, but it is necessary to put it
      into mind there are a few intraductal papillomas even if advanced in age. In this
      report, we present the most senile case with intraductal papilloma in our
      institute.

PMID- 10209934
TI  - A case of cervical myelopathy with developmental canal stenosis at the level of
      the atlas. A case report.
AB  - The craniocervical junction is one of the most common sites of malformations.
      Only three cases of myelopathy due to hypoplasia of atlas have been reported
      previously. Among these malformations, the hypoplasia of atlas was first
      described by Wackenheim in 1974. Although developmental canal stenosis due to the
      hypoplasia of atlas seems to have a tendency of causing the cervical myelopathy,
      only three cases of cervical myelopathy due to this condition have been reported
      previously. A 77-year-old man with severe canal stenosis at the level of the
      atlas is reported. The clinical manifestations were 20-year history of
      progressive gait disturbance and paresis of both upper and lower extremities. The
      spinal cord was markedly compressed at the level of the atlas. The clinical
      manifestations improved after a resection of posterior arch of the atlas.

PMID- 10209935
TI  - Analysis of a model of membrane potential for a skin receptor.
AB  - A linear model for the membrane potential of a nerve ending associated with a
      sense-of-touch skin receptor is formulated and analyzed. Because the nerve has
      cytoplasmic extensions and is stimulated through a membrane strain mechanism, the
      model is a generalized cable equation with linear oblique boundary conditions
      (i.e. boundary conditions involving both time and space derivatives). The model
      is stimulated through a certain conductance parameter. We establish solutions for
      the problem and we consider a particular physiological question, both
      analytically and computationally, of determining conditions on parameters and
      stimulus which give threshold level potential values at a particular boundary
      point.

PMID- 10209936
TI  - Simulations of pertussis epidemiology in the United States: effects of adult
      booster vaccinations.
AB  - An expanded pertussis (whooping cough) vaccination program which includes adult
      boosters every 10 yr is studied using computer simulations of two models. These
      age-structured pertussis transmission models include waning of both infection
      acquired and vaccine-induced immunity, and vaccination of children corresponding
      to the vaccination coverage since 1940. Adult vaccinations cause a larger boost
      in the immunity level in the second model than in the first model. In the
      simulations the addition of adult pertussis booster vaccinations every 10 yr is
      beneficial in reducing adult incidence, but causes only modest reductions in the
      incidence in infants and young children. These simulations suggest that a careful
      cost effectiveness analysis is needed before implementation of an adult pertussis
      vaccination program.

PMID- 10209937
TI  - Stochastic models of telomere shortening.
AB  - Shortening of chromosome ends, known as telomeres, is one of the supposed
      mechanisms of cellular aging and death. We provide a probabilistic analysis of
      the process of loss of telomere ends. The first work concerned with that issue is
      the paper by Levy et al. [J. Molec. Biol. 225 (1992) 951-960]. Their
      deterministic model reproduced the observed frequencies of viable cells in the in
      vitro experiments. Arino et al. [J. Theor. Biol. 177 (1995) 45-57] reformulated
      the model of Levy et al. (1992) in the terms of branching processes with
      denumerable type space. In the present paper, the mathematical results of Arino
      et al. (1995) are extended to the case in which cell death is present, in cells
      with telomeres above and below the critical threshold of length, generally with
      differing probabilities. Both exact and asymptotic results are provided, as well
      as a discussion of biological relevance of the results.

PMID- 10209938
TI  - Nitrite, endothelin and E-selectin plasma levels after arginine infusion in
      normal and vasculopathic subjects.
AB  - BACKGROUND: The authors carried out a study on the simultaneous modifications of
      nitrite, endothelin and E-selectin plasma levels after infusion of arginine (a
      precursor of nitric oxide endothelial synthesis) in normal and vasculopathic
      subjects. METHODS: The series consisted of 24 female subjects (mean age 58 +/- 7)
      of which: 12 normal controls; 12 suffering from chronic cerebral vascular disease
      and coronary heart diseases. Each subject, after a venous blood withdrawal,
      received arginine (20 g over 2 hours); withdrawals were repeated after 60 and 120
      minutes. The levels of total nitrites (NO2-, colorimetric method), endothelin (ET
      1, ELISA method) and E-selectin (E-s, ELISA method) were determined on each
      plasma sample. RESULTS: The levels of NO2-, specific end-products of nitric
      oxide, did not show significant changes after arginine infusion in the
      vasculopathic subjects (group B), whereas in the normal subjects (group A) a
      significant reduction was recorded. The ET-1 levels after arginine did not show
      significant differences between the two groups. The values of E-selectin
      presented no significant variations after arginine in the two groups. The basal
      values of nitrites, endothelin and E-selectin was significantly (p < 0.05) lower
      in group B than in group A. CONCLUSIONS: In conclusion, this study has
      demonstrated that arginine infusion did not alter the nitrite, endothelin and E
      selectin plasma levels within two hours in vasculopathic subjects, suggesting a
      probable wide abiotrophic damage of the endothelial structures. The reduction of
      nitrites after arginine in the normal subjects may depend of an inverse
      organification process due to an enhanced bio-synthesis of nitric oxide.

PMID- 10209939
TI  - Hyperkinetic ventricular arrhythmias in very elderly people with and without
      cardiac disease. Correlation with left ventricular echocardiographic parameters.
AB  - BACKGROUND: Morphological and functional changes induced by aging can hamper a
      clear distinction between pathological or paraphysiological phenomena in very old
      people. The incidence of hyperkinetic ventricular arrhythmias, for example,
      progressively increases in the elderly, even in the absence of overt cardiac
      disease. METHODS: One-hundred fifty-two clinically stable patients older than 80
      years, submitted within 15 days to clinical evaluation, 24-hour continuous
      ambulatory ECG monitoring and echo Doppler examination, in the absence of
      antiarrhythmic treatment, were retrospectively selected in order to evaluate the
      incidence of ventricular arrhythmias, in patients with and without significant
      heart disease. The further aim of the study was to correlate the number of
      arrhythmias with left ventricular morphological and functional parameters,
      echocardiographically assessed. From the initial population, 80 patients (41
      males, age 83 +/- 3 years) had significant heart disease (ischemic, hypertensive
      or valvular): Group I. Seventy-two patients (30 males, age 83 +/- 3 years) had no
      clinical or instrumental signs of heart disease: Group II. RESULTS: Considering
      echocardiographic data, Group I patients had a significantly higher left
      ventricular end-diastolic diameter (52 +/- 6 mm vs 47 +/- 4 mm, p < 0.01), lower
      ejection fraction (57 +/- 10% vs 64 +/- 6%, p < 0.01) and higher mass (275 +/- 84
      g vs 208 +/- 46 g, p < 0.01), when compared with Group II. From ECG monitoring
      data, significant differences between the two groups were recorded in the
      incidence of premature ventricular beats per hour (79 +/- 163 vs 15 +/- 34, Group
      I vs Group II, p < 0.01) and presence of complex phenomena (couplets, triplets
      and runs: 51% vs 22%, p < 0.01). In old patients with documented cardiac disease
      a significant correlation was present between premature ventricular beats
      incidence and left ventricular end diastolic diameter (r = 0.39, p < 0.05) and
      left ventricular ejection fraction (r = 0.40, p < 0.05), while in patients
      without heart disease, no significant correlation was found between incidence of
      premature ventricular beats and echocardiographic morpho-functional parameters.
      CONCLUSIONS: In conclusion, hyperkinetic ventricular arrhythmias are globally
      frequent in old persons of very advanced age (more than 80 years), but, also in
      this subset, a significant distinction in terms of incidence and severity of
      arrhythmias is present between subjects with and without cardiac disease. A
      significant correlation between incidence of premature beats and non-invasive
      morpho-functional left ventricular parameters is present only for patients with
      overt heart disease.

PMID- 10209940
TI  - [Ventricular pre-excitation in Wolff Parkinson White syndrome in the aged].
AB  - AIM: To evaluate any differences in ventricular pre-excitation secondary to Wolff
      Parkinson White syndrome in the aged compared to young and adult patients.
      METHODS:  EXPERIMENTAL DESIGN: a clinical study was performed using a comparative
      prospective criterion with retrospective analysis. The duration of follow-up
      ranged between one and ten years. SETTING: the series was collected from the
      Cardiology Clinic of the Health District and the Cardiology Division of Gorizia,
      both forming part of no. 2 Isontina Health Service. PATIENTS OR PARTICIPANTS: the
      series included 17 patients suffering from Wolff Parkinson White syndrome who
      were divided into two study groups: 9 elderly patients and 8 young patients. The
      latter were subdivided into a first subgroup of 4 cases with Wolff Parkinson
      White syndrome with ECG positive for the presence of delta waves, and a second
      subgroup also with Wolff Parkinson White syndrome secondary to bundle.
      INTERVENTIONS: some young patients with Wolff Parkinson White syndrome who were
      symptomatic for tachycardia underwent ablative surgery with radiofrequency of the
      bundle. PARAMETERS: all patients underwent cardiological screening focused in
      particular on surface electrocardiogram. Those cases with Wolff-Parkinson White
      syndrome with occult bundle underwent transesophageal electrostimulation to find
      the conduction threshold of the anomalous bundle. RESULTS: Adult-elderly
      patients: six subjects were diagnosed with antero-septal and left ventricular
      Kent's bundle (type B common) and 3 cases with Mahaim-Wiston bundle (type A
      rare). Surface ECG revealed the presence of left ventricular hypertrophy in 6
      cases, left anterior hemiblock and total block of the left branch in 3 cases, as
      well as myocardial pseudonecrosis correlated to Wolff Parkinson White syndrome.
      Young patients: four out of this group were affected by Kent's bundle with type B
      Wolff Parkinson White syndrome and the same number suffered from the same
      syndrome caused by occult bundle. Patients in the first subgroup showed an antero
      septal, transitional and left ventricular orientation of Kent's bundle, with the
      onset of 2 cases of orthodromic and antidromic reciprocal rhythm respectively and
      1 case of atrial fibrillation. The refractory nature of the anomalous pathway was
      not very high in 2 cases, equal to 60 milliseconds and 240 milliseconds with the
      proposed ablation of the anomalous bundle.

PMID- 10209941
TI  - Current role of venography in the diagnosis of deep-vein thrombosis.
AB  - The clinical diagnosis of deep vein thrombosis (DVT) is barely sensitive and
      specific. Thus, the clinical suspicion of DVT needs to be confirmed by objective
      testing. Venography has been for a long time the only reliable technique to
      confirm or rule-out the clinical suspicion of DVT. Furthermore, venography served
      as "gold standard" for the validation of non-invasive diagnostic methods for DVT.
      Among these methods, compressive real-time B-mode ultrasonography (CUS) has
      substantially reduced the need of performing venography, mainly in outpatients
      with clinical suspicion of DVT. However, indications for venography still remain
      in the three DVT patient categories. CUS is highly specific in patients with a
      first episode of clinically suspected DVT, so that positive patients can be
      treated with anticoagulants without any further testing. In CUS negative patients
      three options are available in order to rule-out clinically significant DVT: a)
      to repeat CUS at day 2 and 8; b) to associate D-dimer to CUS to rule-out DVT
      (negative D-dimer) or to reinforce surveillance (positive D-dimer); c) to perform
      venography on the same day. This last approach has been proposed in patients with
      negative CUS and high pretest clinical probability. CUS is highly specific in
      high risk patients with asymptomatic DVT and thus it could be used to make
      treatment decision in positive patients. However, CUS is less sensitive in
      asymptomatic than in symptomatic patients. Thus, venography remains the only
      available diagnostic technique to rule-out DVT in asymptomatic patients. In
      clinical practice, venography should be used on individual basis. In clinical
      research on DVT prophylaxis, venography should be used in the assessment of the
      end-point. However, three recent clinical trials on the prevention of post
      discharge DVT has generated some uncertainty on the clinical relevance of
      asymptomatic venography detected DVT. Four to six weeks after discharge a high
      prevalence of venography detected DVT was observed, a finding disagreeing with
      the low incidence of clinically overt thromboembolic events at long-term follow
      up. Two strategies are available in patients with recurrent symptomatic DVT: to
      follow-up patients with serial impedance plethysmograph and CUS after the first
      episode in order to pick-up a positive test in patients previously turned
      negative or to perform venography, a new intraluminal filling defect suggesting
      DVT recurrence.

PMID- 10209942
TI  - Frequent allelic loss on chromosome 9 in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a common malignancy worldwide and highly
      associated with chronic virus-B or -C infection and cirrhosis. Molecular studies
      have shown high frequency of loss of heterozygosity (LOH) in some specific
      chromosome regions, but LOH on chromosome 9 in HCC has not been thoroughly
      investigated. In our investigation of chromosome 9 with 19 polymerase-chain
      reaction (PCR)-based polymorphic microsatellite markers, 30 of 48 HCC tissue
      samples (63%) had LOH, and a distinct common deletion region and a region of loss
      were identified. The first region was located at the 9p21 region and the minimal
      deletion region was located between loci D9S1747 and D9S1748. This is a region of
      approximately 200 kb which includes the p16 tumor-suppressor gene. A region of
      loss was located on 9p13 to 9q33. The putative tumor-suppressor gene for nevoid
      basal-cell-carcinoma syndrome (NBCCS) at 9q22.3 resides within this region. In
      addition to LOH, 4 HCC cases showed possible homozygous deletions at 9p21 with
      markers D9S1748, D9S1752 and D9S171 by multiplex PCR analysis. In 3 cases, the
      minimal region of possible homozygous deletion was approximately 300 kb and was
      defined between markers D9S1747 and D9S1752. Since this deletion region includes
      both the p15 and the p16 tumor-suppressor genes, these genes were possibly
      inactivated by homozygous deletion in HCC. In addition, a second region of
      possible homozygous deletion was present on the centromeric side of 9p21.
      However, these changes are not associated with age, gender, size or tumor-cell
      differentiation. Our data also suggest that inactivation of the p16 and the p15
      genes and the possibility of other unknown tumor-suppressor genes located on
      these defined deleted regions of chromosome 9 may be involved in the pathogenesis
      of HCC.

PMID- 10209943
TI  - Genetic polymorphism of xenobiotic metabolizing enzymes among Chinese lung cancer
      patients.
AB  - Polymorphisms in xenobiotic metabolizing enzymes have been implicated in inter
      individual and inter-ethnic differences in cancer susceptibilty. Several studies
      have indicated an association between variant alleles of the human CYP1A1, CYP2E1
      and GSTM1 genes and lung cancer. Activity of microsomal epoxide hydrolase (HYL1)
      has also been associated with lung cancer, and 2 variant alleles causing amino
      acid substitutions have been described. We have investigated genetic
      polymorphisms of the CYP1A1, CYP2E1, GSTM1 and HYL1 genes in 76 Chinese lung
      cancer patients and 122 healthy Chinese subjects. The allele frequency of the
      CYP1A1*2B allele was 0.21 among lung cancer patients and 0.20 in the reference
      group, whereas the corresponding values for the CYP1A1*2A allele were 0.34 and
      0.36. The CYP2E1*5B and CYP2E1*6 alleles were less frequent among the cancer
      patients (0.20 and 0.22) compared with healthy subjects (0.25 and 0.26). The
      frequency distribution of the HYL1*2 allele was 0.49 among lung cancer patients
      and 0.42 in the reference group, and the corresponding frequencies for the HYL1*3
      allele were 0.13 and 0.10. The homozygous GSTM1*0 genotype was found in 64% of
      lung cancer patients and in 66% of healthy subjects. Among heavy smokers, the
      frequency was 73%. The differences in the distribution of variant CYP1A1, CYP2E1
      and GSTM1 alleles in lung cancer patients and healthy controls were not
      statistically significant. Our results indicate that the polymorphisms
      investigated are of minor importance as genetic susceptibility markers for lung
      cancer in this population. An increased risk for lung cancer in subjects carrying
      the HYL*3 allele was observed and suggests that polymorphism in this gene might
      possibly be a susceptibility factor in the Chinese population.

PMID- 10209944
TI  - Geographical clustering of human T-cell lymphotropic virus type I in Guadeloupe,
      an endemic Caribbean area.
AB  - Between January 1989 and December 1996, 59,426 blood donors from Guadeloupe
      (French West Indies) were screened for antibodies to human T-cell lymphotropic
      virus type I (HTLV-I). Of these, 195 were confirmed as being positive for HTLV-I,
      yielding an overall prevalence of 0.33% [95% confidence interval (CI) 0.28-0.38].
      On multiple logistic regression analysis, risk factors for HTLV-I were female
      gender [odds ratio (OR) 1.8; CI 1.3-2.4], increasing age (30-39 years, OR 2.2, CI
      1.4-3.4; 40-49 years, OR 3.1, CI 2.1-4.7; > or =50 years, OR 5.6, CI 3.6-8.6) and
      positive hepatitis B core antibodies (OR 2.0; CI 1.5-2.8). HTLV-I seropositivity
      was also significantly associated with current residence in certain areas,
      highlighting microgeographic clustering: individuals living along the Atlantic
      Facade of Guadeloupe, which is a traditional sugar cane plantation area where
      Africans were brought during slave trading, were at increased risk for HTLV-I
      infection (OR 1.9; CI 1.3-2.7) compared with other areas in Guadeloupe devoted to
      other activities. Our report of HTLV-I cluster identification in Guadeloupe
      probably reflects both its low spread and its highly intrafamilial restricted
      transmission within this endemic Caribbean population.

PMID- 10209945
TI  - Gender of offspring and maternal breast cancer risk.
AB  - A high total number of full-term pregnancies is associated with a reduced risk of
      breast cancer, though pregnancy transiently increases the risk of the disease.
      However, little attention has been given to a possible association of breast
      cancer risk with the gender of offspring, even though male fetuses have been
      associated with several factors linked to a low breast cancer risk, namely,
      pregnancy toxemia, increased levels of alpha-fetoprotein (AFP) and increased
      levels of sex hormone-binding globulin. We used data from linked Swedish
      registries to study the relative importance of male and female offspring as risk
      correlates of subsequent breast cancer in the mothers. In a nested case-control
      study, case patients were 2,328 women who had one or more live-born children
      delivered between 1973 and 1989 and who were subsequently diagnosed with breast
      cancer during this period. For comparison, 10,256 control subjects, matched to
      cases by birth year, were randomly selected from among the eligible women. Number
      of boys was inversely associated and number of girls positively associated with
      breast cancer risk. Neither of these trends was significantly different from the
      null value, but the difference between the 2 trends was marginally significant
      (p=0.06). Moreover, women who gave birth to 2 or more boys but no girls were at
      significantly lower risk for breast cancer in comparison to women who gave birth
      to 2 or more girls but no boys; the odds ratio was 0.78 (95% CI 0.64-0.95). The
      apparently protective effect of pregnancies with male fetuses was limited to
      women younger than 40 years. Endocrine or other metabolic processes specifically
      associated with a male rather than a female fetus may impart relative protection
      against the occurrence of breast cancer during the childbearing period.

PMID- 10209946
TI  - Breast-cancer risk following long-term oestrogen- and oestrogen-progestin
      replacement therapy.
AB  - While use of hormone-replacement therapy (HRT) effectively alleviates menopausal
      symptoms and prevents osteoporosis and possibly cardiovascular disease, there is
      concern of a detrimental impact on breast-cancer risk. There is a particular lack
      of data regarding the effect of long-term use of oestrogen-progestin combinations
      on breast-cancer risk. We conducted a large epidemiological study in Sweden,
      where combined oestrogen-progestin treatment has been predominant, to examine the
      influence of different regimens of menopausal hormone therapy on breast-cancer
      risk. In this population-based case-control study, 3,345 women aged 50 to 74
      years with invasive breast cancer (84% of all eligible) and 3,454 controls of
      similar age (82% of all selected) were included. Mailed questionnaires and
      telephone interviews were used to collect detailed information on use of hormone
      replacement and on potential confounding factors. Odds ratios (OR) and 95%
      confidence intervals (CI) were estimated through multiple logistic regression.
      There was a trend of increasing breast-cancer risk with duration of
      oestrogen/oestrogen-progestin use (OR for women treated at least 10 years, 2.43;
      95% CI, 1.79-3.30, as compared to never-users), with statistically significant
      estimates only for women with BMI<27 kg/m2. Excess risks were observed to current
      use and use that ceased more than 10 years ago (OR for women treated at least 5
      years, OR was 2.68, 95% CI, 2.09-3.42, and OR 2.57, 95% CI, 1.28-5.15, as
      compared with never-users, respectively). A positive association which was noted
      for use of oestrogen combined with testosterone-derived progestins appeared
      especially pronounced with continuously combined regimens. Long-term use of
      replacement oestrogens with or without progestins may substantially increase the
      incidence of post-menopausal breast cancer, particularly among non-obese women.

PMID- 10209947
TI  - Molecular analysis of glioma and skin-tumour alterations in a xeroderma
      pigmentosum child.
AB  - Xeroderma pigmentosum (XP) is a rare hereditary disease characterized by a very
      high frequency of skin tumours due to a defect in the nucleotide-excision-repair
      process. Some of these patients have also been reported to develop internal
      tumours with higher frequency than the normal population. Reported here are the
      clinical features and molecular analysis of an XP patient who developed multiple
      skin cancers as well as a thalamic glioma. Complementation analysis with
      recombinant retrovirus, cloning efficiency and unscheduled DNA synthesis after UV
      C indicate that the patient belongs to the C group. Characterization of the p53
      mutations in the 2 tumours of the patient leads to speculation on the
      aetiological agents involved in tumour initiation. The skin tumour is clearly
      induced by the presence of unrepaired UVB-induced DNA damage on the non
      transcribed strand of the p53 gene, while the glioma may be induced by unrepaired
      DNA lesions produced by free radicals.

PMID- 10209948
TI  - Genital talc exposure and risk of ovarian cancer.
AB  - Epidemiologic studies have suggested an increased risk for ovarian cancer
      associated with the use of talcum powder in genital hygiene, but the biologic
      credibility of the association has been questioned. We conducted a population
      based case-control study in eastern Massachusetts and New Hampshire involving 563
      women with newly diagnosed epithelial ovarian cancer and 523 control women
      selected either by random digit dialing or through lists of residents. Use of
      body powders was assessed through personal interview and the exposure odds ratio
      (OR) for the use of talc in genital hygiene was calculated. Cases were more
      likely than controls (45% vs. 36%) to have used talc as a body powder in some
      manner, and the excess was confined to patients who used talc on the perineum
      directly or as a dusting powder to underwear or sanitary napkins. Relative to
      women who never used body powder or used it only in non-genital areas, the OR
      (and 95% confidence interval) associated with genital exposure to talc was 1.60
      (1.18 and 2. 15) after adjustment for age, study location, parity, oral
      contraceptive use, body mass index and family history of breast or ovarian
      cancer. Exposure prior to rather than after a first livebirth appeared to be more
      harmful, and the association was most apparent for women with invasive serous
      cancers and least apparent for those with mucinous tumors. We conclude that there
      is a significant association between the use of talc in genital hygiene and risk
      of epithelial ovarian cancer that, when viewed in perspective of published data
      on this association, warrants more formal public health warnings.

PMID- 10209950
TI  - Familial aggregation of astrocytoma in northern Sweden: an epidemiological cohort
      study.
AB  - This population-based cohort study investigated the occurrence of familial
      astrocytoma among first-degree relatives of patients with astrocytoma diagnosed
      between 1985 and 1993 in the northern region of Sweden. The 432 cases received a
      questionnaire. They were asked to provide names and cancer diagnoses of first
      degree relatives. Of the 297 answering, a cohort was constructed of their 1,890
      first-degree relatives (FDR). A significantly increased risk [standardized
      incidence ratio, SIR = 2.12, 95% confidence interval (CI) = 1.18-3.49] was shown
      for developing primary brain tumors (PBT). In 4.7% (14/297) of the families, a
      PBT was found. Interestingly, the increased risk was for astrocytoma only (SIR =
      3.12, 95% CI 1.42-5.92), and not for other PBT (SIR 0.90, 95% CI 0.18-2.64). When
      the cohort was divided according to the median age of proband, most of the
      increased risk was restricted to the younger cohort (SIR = 4.71, 95% CI 1.52
      10.99). Surprisingly, a significantly decreased risk for breast cancer and colon
      cancer was shown. The finding that the increased risk is restricted to
      astrocytoma only is a novel one. This study implies that familial aggregation of
      astrocytoma exists; the familial clustering occurs in a small fraction of
      astrocytoma, and might be explained by inherited factors.

PMID- 10209949
TI  - Smoking and oral contraceptives as risk factors for cervical carcinoma in situ.
AB  - Human papillomavirus (HPV) is probably a necessary but definitely not a
      sufficient cause of cervical carcinoma. However, it remains unclear which
      factors, in addition to HPV, are important for the development of cervical
      carcinoma and its precursor lesions. To address this issue, we conducted a case
      control study nested in a population-based cohort consisting of women
      participating in cytological screening in one Swedish county, any time during
      1969 through 1995. Detailed information on sexual practice, smoking habits and
      oral contraceptive (OC) use were collected through telephone interviews with 422
      case patients diagnosed with cervical carcinoma in situ and 422 control subjects.
      All cytological smears were analyzed for presence of HPV 16/18 by a polymerase
      chain reaction (PCR)-based method. Odds ratios (OR) were used as measures of
      relative risk. After multivariate adjustment, a 2-fold higher risk was observed
      among current smokers compared with never smokers [OR 1.94; 95% confidence
      interval (CI 1.32-2.85)], an association apparently confined to women younger
      than 45 years. Current use of OCs was associated with a 4-fold increased risk
      overall (OR 3.64; 95% CI 1.91-6.93) with a monotonic increase with increasing
      duration of use (p for trend < 0.001). The number of sexual partners was
      significantly, positively associated with risk among HPV 16/18-negative (p for
      trend < 0.005) but not among HPV 16/18-positive women. Our data confirm the
      association between smoking and cervical carcinoma in situ, which might be age
      dependent. Our results further indicate a relation with OC use and the risk for
      cervical carcinoma in situ.

PMID- 10209951
TI  - Sequence polymorphisms between latent membrane proteins LMP1 and LMP2A do not
      correlate in EBV-associated reactive and malignant lympho-proliferations.
AB  - The latent membrane proteins LMP1 and LMP2A are co-expressed in most malignancies
      associated with Epstein-Barr virus (EBV). In contrast with the transforming LMP1
      oncoprotein, LMP2A is expressed in lymphocytes of healthy EBV carriers and
      considered to maintain viral latency. Critical for these LMP2A functions are a
      transmembranous epitope recognized by specific cytotoxic T lymphocytes (CTLs) and
      the N-terminal immunoreceptor tyrosine-based activation motif (ITAM), blocking B
      cell receptor signaling. To characterize ITAM and CTL motifs of LMP2A and to
      correlate them with C-terminal variants of LMP1 including the 30-bp deletion
      variant (LMP1delta), comparative sequence analysis was performed on 76 samples
      from patients with reactive and malignant lympho-proliferation (infectious
      mononucleosis, n=21; tonsillar hyperplasia, n=16, chronic lympho-proliferation, n
      = 9; Hodgkin's disease, n = 8; Non-Hodgkin's lymphoma, n = 5; AIDS-related large
      cell lymphoma, n=17). The CTL motif was conserved in all but 2 cases (C426-->S).
      The ITAM motif was characterized by strictly conserved YXXL sequences in all
      cases, with a sequence polymorphism in between. The B95.8 prototype was found in
      17% (13/76) of cases, while in 72% a variant with 3 point mutations (166796 C-
      >A, 166805 C-->A, 166810 C-->T) was detected; 11% had 1 or 2 of these mutations
      in addition to G-->A at 166793. In the C terminus of LMP1, a hypervariable region
      including LMP1delta was described in 61% of cases. There was no significant
      association of a particular LMP2A variant with either malignant phenotype or
      LMP1delta, demonstrating that the functional domains of LMP2A are conserved and
      that the sequence polymorphisms in LMP1 and LMP2A are independent.

PMID- 10209952
TI  - Receptor autoradiographic evaluation of cholecystokinin, neurotensin,
      somatostatin and vasoactive intestinal peptide receptors in gastro-intestinal
      adenocarcinoma samples: where are they really located?
AB  - Receptors for cholecystokinin (CCK), gastrin, neurotensin, somatostatin and
      vasoactive intestinal peptide (VIP) are over-expressed in several human tumors,
      where they have diagnostic and therapeutic implications. Since reports on the
      expression of these peptide receptors in primary gastric and colonic
      adenocarcinomas are either non-existent or conflicting, a detailed evaluation
      with particular emphasis on the tissue localization was undertaken. CCK-A, CCK-B,
      neurotensin, somatostatin and VIP receptors were localized by in vitro receptor
      autoradiography with iodinated radioligands on histological sections of surgical
      samples of 27 gastric and 25 colonic adenocarcinomas. CCK-A, CCK-B and
      neurotensin-1 receptors were found in a minority of both tumor types.
      Somatostatin receptors were found in 18/27 gastric and 2/25 colonic cancers. VIP
      receptors were found in 14/26 gastric and 23/25 colonic cancers; subtype
      characterization suggests VIP1 receptors. In addition, resected tumor samples
      contained non-malignant tissues (mucosa, smooth muscle, nerves or vessels) with
      high amounts of the various peptide receptors. Therefore, regulatory peptide
      receptors are expressed differentially in gastric and colonic cancers but also
      very frequently in "contaminating" non-malignant tissues. Since results using
      morphological techniques are superior to those using homogenates, we recommend
      that localization of these receptors to the tissues should always be attempted,
      to minimize receptor over-estimation in tumors and to prevent spurious results.

PMID- 10209953
TI  - A newly identified MAGE-3-derived epitope recognized by HLA-A24-restricted
      cytotoxic T lymphocytes.
AB  - Five MAGE-3-derived peptides carrying an HLA-A24-binding motif were synthesized.
      Binding capacity of these peptides was analyzed by an HLA-class-I stabilization
      assay. Two of the 5 peptides bound to HLA-A*2402 molecule with high affinity, and
      3 peptides with low affinity. Peripheral-blood mononuclear cells (PBMC) depleted
      of CD4+T cells were stimulated with the peptides to determine whether these
      peptides would induce cytotoxic T lymphocytes (CTL) from PBMCs obtained from 7
      healthy HLA-A*2402+ donors. Peptide M3-p97 (TFPDLESEF; corresponding to amino
      acid residues 97-105 of MAGE-3), with high binding capacity to the HLA-A*2402
      molecule, elicited the peptide-specific and HLA-A24-restricted CD8+CTL lines in 2
      of the 7 donors, while none of the 4 other peptides induced CTL specific for the
      corresponding peptide in any of the donors. CTL lines induced by stimulation with
      peptide M3-p97 exhibited cytolytic activities against HLA-A*2402 transfectant
      cell lines (C1R-A*2402) in the presence of peptide M3-p97, but not in unloaded or
      irrelevant peptide-pulsed C1R-A*2402 cells. The CTL lines and a cloned CD8+CTL
      isolated from one of the bulk populations by limiting dilution could lyse MAGE
      3+/HLA-A*2402+ squamous-cell-carcinoma(SCC) lines but neither MAGE-3-/HLA-A*2402+
      nor MAGE-3+/HLA-A*2402- SCC lines, indicating that M3-p97 can be naturally
      processed and presented on the tumor-cell surface in association with HLA-A*2402
      molecules. Combined with the 4 currently reported CTL epitopes derived from MAGE
      3 and presented by HLA-A1, HLA-A2, HLA-A24 or HLA-B44, identification of this CTL
      epitope presented by the HLA-A*2402 molecule will extend the application of MAGE
      3-derived peptides for immunotherapy for cancer patients.

PMID- 10209954
TI  - Osteoblast conditioned media contain TGF-beta1 and modulate the migration of
      prostate tumor cells and their interactions with extracellular matrix components.
AB  - Prostate cancers (PRCAs) frequently metastasize to bone. We show here that this
      process is facilitated by osteoblast-mediated tumor cell recruitment.
      Transforming growth factor-beta1 (TGF-beta1) is produced by osteoblasts in a
      latent form and is activated by proteases in a cell-dependent manner. This
      cytokine exhibits pleiotropic effects on cell-extracellular matrix (ECM)
      interactions and may influence tumor cell invasion and metastasis. Our purpose
      was to identify the potential molecular mechanisms involved in osteoblast
      mediated cell recruitment and to characterize the effect of TGF-beta1 on
      adhesion, motility and invasiveness of a human prostate cancer cell line with
      high bone metastatic potential (PC3 cell line) in vitro. Conditioned media from
      osteoblast cultures (OB CM) enhanced PC3 cell chemotaxis and invasion of
      reconstituted basement membrane. These effects were blocked by a neutralizing TGF
      beta1 polyclonal antibody but not by elution of the OB CM in agarose-heparin
      columns, suggesting that TGF-beta1, but not EGF-like proteins, contribute to PC3
      cell recruitment. In addition, TGF-beta1 directly induced chemotaxis and invasion
      of PC3 cells in a dose-dependent manner. The TGF-beta1-mediated invasion and
      motility were accompanied by increased PC3 cell adhesion, spreading and
      alpha2beta1 and alpha3beta1 integrin expression. These events are involved in the
      cell adhesion to several components of basement membrane and ECM and in the
      selective invasion of metastatic tumor cells. Our results suggest that TGF-beta1
      can influence cellular recognition of ECM components by prostatic cancer cells
      and can modulate cell adhesion and invasion leading to increased invasive
      potential. Given the widespread tissue distribution of TGF-beta1, and the high
      levels present in the bone, this cytokine may be an important autocrine-paracrine
      modulator of the bone invasive phenotype in vivo.

PMID- 10209955
TI  - Enhanced cell motility and invasion of chicken embryo fibroblasts in response to
      Jun over-expression.
AB  - Malignant tumor cells exhibit a number of distinct properties involved not only
      with deregulated cell proliferation but also enhanced migration and invasion. The
      Jun oncogene has been well studied in regard to its role in cell proliferation.
      Many of the target genes deregulated by Jun encode matrix metalloproteases (MMPs)
      such as MMP1, MMP3 and MMP9. These targets implicate a prominent role for Jun in
      tumor cell invasion, in addition to its role in growth transformation. To
      investigate this possibility, we have examined the effect of over-expression of
      transforming and non-transforming versions of Jun on motility and invasion of
      chicken embryo fibroblasts (CEFs). We found that over-expression of either form
      of Jun results in elevated intrinsic cellular motility as well as increased
      motility in response to several different chemo-attractants, including 3T3
      conditioned media, basic fibroblast growth factor, hepatocyte growth factor and
      Matrigel. The capacity of these cells to invade through Matrigel is also elevated
      as a result of Jun over-expression. In addition to these effects, CEFs expressing
      Jun secrete factors that stimulate the motility of a human tongue carcinoma cell
      line. Our results suggest that Jun plays an important role in the potentiation of
      cell motility and invasion through multiple mechanisms.

PMID- 10209956
TI  - Hyaluronic acid as drug delivery for sodium butyrate: improvement of the anti
      proliferative activity on a breast-cancer cell line.
AB  - The potential clinical utility of sodium butyrate, a natural compound known to
      inhibit tumor-cell growth, is hampered by the difficulty of achieving effective
      in-vivo concentrations. The short half-life (about 5 minutes) of sodium butyrate
      results in rapid metabolism and excretion. To increase the availability of sodium
      butyrate over a longer period of time, we co-valently linked it to hyaluronic
      acid (a component of the extracellular matrix). Its major advantages as a drug
      carrier consist in its high biocompatibility and its ability to bind CD44, a
      specific membrane receptor frequently over-expressed on the tumor-cell surface.
      The degree of substitution of hyaluronic acid with butyrate residues ranged from
      d.s.=0.10 to d.s.=2.24 (1.8-28.4% w/w). The biological activity of hyaluronic
      acid-butyric-ester derivatives was evaluated in terms of the inhibition of the
      growth of the MCF7 cell line and compared with that of sodium butyrate. After 6
      days of treatment, we observed a progressive improvement of the anti
      proliferative activity up to d.s.=0.20; thereafter, the anti-proliferative effect
      of the ester derivatives decreased. Fluorescence microscopy showed that after 2
      hr of treatment fluorescein-labelled compounds appeared to be almost completely
      internalized into MCF7 cells, expressing CD44 standard and variant isoforms.
      These findings indicate that hyaluronic acid could offer an important advantage
      in drug delivery, in addition to its biocompatibility: the ability to bind to
      CD44, which are known to be frequently over-expressed on the tumor-cell surface.

PMID- 10209957
TI  - Neurotrophins and Trk receptors in human pancreatic ductal adenocarcinoma:
      expression patterns and effects on in vitro invasive behavior.
AB  - The aggressive and highly metastatic behavior observed in pancreatic ductal
      adenocarcinoma (PDAC) may be due to autocrine and/or paracrine interactions
      (tumor/stromal) involving altered expression of peptide growth factors and their
      corresponding receptors. The neurotrophin (NT) growth factor family and their
      cognate receptors have been demonstrated to play a role in the invasiveness,
      chemotactic behavior and tumor cell survival of both neuronal and non-neuronal
      cancers. We hypothesized that aberrant expression of the NTs and/or the Trk
      receptors may contribute to the malignant phenotype of PDAC, specifically tumor
      cell invasiveness, through autocrine and/or paracrine interactions. In this
      study, we examined the expression of NTs, Trks and p75NGFR by immunohistochemical
      and in situ hybridization analyses in both normal (n=14) and neoplastic pancreas
      (n=47) and PDAC-derived cell lines (n=6). Further, we evaluated the effects of
      various NTs on the in vitro invasive and chemotactic behavior on 6 human PDAC
      derived cell lines in a modified Boyden chamber assay. Brain-derived nerve growth
      factor (BDNF), NT-3, NT-4/5 and Trks A, B and C exhibited diffuse cytoplasmic and
      membranous immunostaining patterns in both the ducts and the acini of the
      exocrine pancreas and the islets of the endocrine pancreas of both normal and
      PDAC specimens. NT expression was primarily within the stromal compartment of the
      tumor, while Trk expression was weak or absent. We observed a 68%, 64% and 66%
      increase in the expression of Trks A, B and C, respectively, in the ductal
      elements of the PDAC samples examined compared with the normal adjacent tissue.
      Invasiveness of 4 of 6 PDAC cell lines was significantly inhibited (p<0.05) when
      the cells were incubated with 100 ng/ml NT. However, when select cell lines were
      incubated with lower concentrations of NT-3 and BDNF (0, 1, 5, 25 and 50 ng/ml),
      invasiveness was significantly stimulated (p<0.05) through the Matrigel matrix.
      Collectively, our data suggest the possibility that paracrine and/or autocrine NT
      Trk interactions may influence the phenotype (possibly the invasive behavior) of
      PDAC.

PMID- 10209958
TI  - Interleukin-12-secreting human papillomavirus type 16-transformed cells provide a
      potent cancer vaccine that generates E7-directed immunity.
AB  - The development of a vaccine that would be capable of preventing or curing the
      (pre)cancerous lesions induced by genital oncogenic human papillomaviruses (HPVs)
      is the focus of much research. Many studies are presently evaluating vaccines
      based on the viral E6 and E7 oncoproteins, both of which are continually
      expressed by tumor cells. The success of a cancer vaccine relies, in large part,
      on the induction of a tumor-specific Th1-type immunity. In this study, we have
      evaluated the ability of B7-related and/or interleukin-12 (IL-12)-expressing, non
      immunogenic murine HPV16-transformed BMK-16/myc cells, to achieve this goal. BMK
      16/myc cells engineered to express surface B7-1 or B7-2 molecules remain
      tumorigenic in syngeneic BALB/c mice, suggesting that expression of these
      molecules alone is not sufficient to induce tumor regression. In contrast, mice
      injected with tumor cells engineered to secrete IL-12 remained tumor-free,
      demonstrating that IL-12 expression is sufficient to induce tumor rejection. IL
      12-secreting BMK-16/myc cells were further shown to induce potent and specific
      long-term tumor resistance, even after irradiation. B7-1 was found to slightly
      but systematically improve anti-tumor immunity elicited by IL-12-secreting BMK
      16/myc cells. Injection of irradiated B7-1/IL-12+ BMK-16/myc cells generates long
      lasting, Th1-type, BMK-16/myc-directed immunity in tumor-resistant mice. These
      mice display a memory-type, E7-specific, cell-mediated immune response, which is
      potentially significant for clinical applications.

PMID- 10209959
TI  - Prostatic human kallikrein 2 inactivates and complexes with plasminogen activator
      inhibitor-1.
AB  - Human kallikrein 2 (hK2) is a serine protease expressed predominantly in the
      prostate which has 80% homology to prostate-specific antigen (PSA). hK2 is an
      active trypsin-like protease which has been shown by immuno-histochemical
      staining to be more highly expressed in prostate carcinoma than in benign
      prostate tissue. Unlike PSA, hK2 activates pro-PSA , pro-hK2 and the zymogen form
      of urokinase-type plasminogen activator (uPA), an extracellular protease
      correlated with prostate cancer and metastasis. We show here that hK2 rapidly
      forms a complex with plasminogen activator inhibitor-1 (PAI-1), the primary
      inhibitor of uPA in tissues. In addition, hK2 inactivated 6 to 7 mol of PAI-1 by
      cleavage at Arg346-Met347 for every mole of hK2-PAI-1 complex formed. In contrast
      with hK2, PSA neither complexed with nor inactivated PAI-1. PAI-1 inhibited hK2
      comparably with protein C inhibitor (PCI) and at least 20 times more rapidly than
      alpha1-anti-chymotrypsin (ACT). N-Terminal sequencing shows that hK2 forms a
      covalent complex with PAI-1, PCI and ACT after cleavage at Arg346-Met347, Arg354
      Ser355 and Leu358-Ser359, respectively. During complex formation, hK2 inactivated
      PAI-1 but did not inactivate ACT or PCI. Our current results suggest that the
      increased hK2 expression in prostate cancer tissues could influence cancer
      biology not only by activation of uPA but also by inactivation of its primary
      inhibitor, PAI-1.

PMID- 10209960
TI  - Transcriptional regulation of urokinase (uPA) gene expression in breast cancer
      cells: role of DNA methylation.
AB  - Carcinoma of the breast is a leading hormone-dependent malignancy, resulting in a
      high rate of morbidity and mortality. During the complex multi-step process of
      tumor promotion, this common cancer is initiated as hormone-responsive (HR), non
      metastatic cancer, followed by a gradual transition into a highly metastatic
      hormone-insensitive (HI) variety which lacks the functional estrogen receptor.
      This transition of cancer cells causes them to become refractory to hormonal
      treatment. Urokinase (uPA), a member of the serine protease family has been
      implicated in the progression of several malignancies including breast cancer. In
      the current study, we have examined the correlation between hormone sensitivity
      and uPA expression in HR normal mammary epithelial cells (HMEC) and in MCF-7 and
      T-47D breast cancer cell lines. Comparison was made with HI breast cancer cells
      MDA-231. uPA mRNA expression was seen only in the highly invasive, HI breast
      cancer cells MDA-231. Lack of uPA expression in HR normal (HMEC) and in minimally
      invasive, HR cells (MCF-7 and T-47D) was due to transcriptional suppression of
      uPA gene expression as determined by nuclear run-off assays. Since alteration of
      the DNA methylation status of CpG island in the 5' sequence of oncogenes and
      tumor suppressor genes has been demonstrated to change their expression, we
      examined DNA methylation as a potential molecular mechanism for regulating uPA
      gene transcription in these cancer cells. Southern blot analysis using
      methylation sensitive enzymes revealed that CpG island of uPA gene are methylated
      in HR, HMEC, MCF-7 and T-47D cells, whereas they are hypomethylated in HI and MDA
      231 cells. Treatment of HR MCF-7 cells with cytosine DNA methyltransferase
      inhibitor 5' azacytidine caused a dose-dependent induction of uPA mRNA due to
      demethylation of the CpG island of the uPA gene which led to increased invasive
      ability of these HR cancer cells. Our results demonstrate that DNA methylation
      can regulate the transcription of the uPA gene to alter the invasive behaviour of
      these HR breast cancer cells.

PMID- 10209961
TI  - Prevalent expression of fibroblast growth factor (FGF) receptors and FGF2 in
      human tumor cell lines.
AB  - Basic fibroblast growth factor (FGF2) has potent mitogenic and angiogenic
      activities that have been implicated in tumor development and malignant
      progression. The biological effects of FGF2 and other members of the FGF ligand
      family are mediated by 4 transmembrane tyrosine kinase receptors (FGFRs). To
      better understand the roles of FGFRs in cancer, the expression of FGF2 and each
      of the 4 FGFRs was assessed by RNase protection analysis of 60 human tumor cell
      lines, representing 9 tumor types. Expression of at least one FGFR isoform was
      detected in 90% and FGF2 mRNA in 35% of the cell lines. Our comprehensive
      analysis of FGF2 and FGFR expression in human tumor cell lines provides evidence
      that FGF signaling pathways are active in a majority of human tumor cell lines,
      and lends support to the development of anti-tumor strategies that target FGFRs.

PMID- 10209962
TI  - Identification of a SART-1-derived peptide capable of inducing HLA-A24-restricted
      and tumor-specific cytotoxic T lymphocytes.
AB  - We have described the SART-1 gene-encoding peptides recognized by HLA-A2601
      restricted and tumor-specific cytotoxic T lymphocytes (CTLs). We now have
      investigated whether SART-1 encodes peptides capable of inducing the HLA-A24
      restricted CTLs. Among the 18 different peptides with HLA-A24-binding motifs, the
      SART-1(690-698) peptide (EYRGFTQDF) was most strongly recognized by the HLA-A24
      restricted and tumor-specific CTLs established from an esophageal cancer patient.
      After a third stimulation in vitro, this peptide induced HLA-A24-restricted CTLs
      recognizing the SART-1(259)+ tumor cells in PBMCs of all HLA-A24 homozygous and
      the majority of HLA-A24 heterozygous cancer patients and healthy donors tested. A
      similar activity, induction of CTLs from PBMCs, was observed in the Saccharomyces
      cerevisiae-derived nonapeptide (EYRGFTPMF) that shares 7 amino acids with the
      SART-1(690-698) peptide. The SART-1(690-698) peptide-induced CTL activity was
      significantly higher in PBMCs of HLA-A24 homozygotes than in HLA-A24
      heterozygotes. The CTL precursor frequency in PBMCs after a third stimulation in
      vitro with the SART-1(690-698) peptide was high (>1/200) in both cancer patients
      and healthy donors. The SART-1(690-698) peptide could thus be useful for specific
      immunotherapy of HLA-A24+ cancer patients.

PMID- 10209963
TI  - Positive and negative interaction of 1,25-dihydroxyvitamin D3 and the retinoid
      CD437 in the induction of human melanoma cell apoptosis.
AB  - The natural ligands of the nuclear receptors vitamin D receptor (VDR) and
      retinoic acid receptor (RAR), i.e., 1alpha,25-dihydroxyvitamin D3 (VD) and all
      trans retinoic acid, have important effects on the proliferation, differentiation
      and apoptosis of a variety of malignant cells, including melanoma. The
      therapeutic potential of the 2 nuclear hormones can be enhanced by the use of
      synthetic analogues. In this study, the 2 human melanoma cell lines WM1341 and
      MeWo were compared for the combined effect of VD and synthetic retinoids. Both
      cell lines expressed reasonable amounts of VDR, RARgamma and retinoid X receptor
      alpha and differed only in the relative expression of RARalpha and beta. From 9
      functional variants of retinoids, only the RARgamma-selective retinoid CD437
      showed, in both cell lines, a significant anti-proliferative effect. In MeWo
      cells, but not in WM1341 cells, VD induced growth arrest but showed no
      synergistic interaction with the effects of CD437. In contrast, VD induced
      apoptosis in WM1341, but not in MeWo, cells. CD437 was a strong inducer of
      apoptosis in both melanoma cell lines. Parallel treatment with CD437 and VD
      resulted in synergistic enhancement of apoptosis in WM1341 cells, whereas a clear
      decrease in induction of apoptosis in MeWo cells occurred. Our results indicate
      that a combined treatment of melanoma with VD and selected retinoids is promising
      but should be adapted to individual types of tumor.

PMID- 10209964
TI  - Transfection of anti-sense complementary DNA of human epidermal-growth-factor
      receptor attenuates the proliferation of human non-small-cell-lung-cancer cells.
AB  - The proliferation of human non-small-cell-lung-cancer (NSCLC) cells is regulated
      by the epidermal-growth-factor-receptor (EGFR)-mediated autocrine loop that
      interacts with transforming growth factor-alpha (TGF-alpha) of autocrine or
      paracrine origin. We have shown that EGFR expression is elevated in the brain
      metastatic variant of human NSCLC cells H226Br, which thereby acquire their
      increased sensitivity toward exogenous TGF-alpha. To determine detailed cell
      phenotype changes as a result of EGFR down-regulation, H226Br cells were
      transfected with a human EGFR-cDNA construct encompassing an N-terminal fragment
      (1.8 kb) in anti-sense orientation downstream of the cytomegalovirus (CMV)
      promoter. The EGFR transcript expressed in the 3'-5' direction is expected to
      neutralize EGFR mRNA and to reduce protein expression correspondingly. The
      established cell lines resistant to G418 were shown integrated with the
      transfected construct and their proliferation rates reduced as compared with the
      parental cells and with those transfected with vector alone. Down-regulated EGFR
      expression in cells with the anti-sense construct can be confirmed by Scatchard
      analysis and suppressed EGFR kinase activity. The restrained-growth phenotype is
      also demonstrated in the prolonged G2-M phase during the cell cycle, and
      correlated with impairment of cell proliferation. This finding suggests that EGFR
      over-expression is critical in maintaining the malignant phenotype of NSCLC
      cells, thereby providing a valuable biomarker and potential target prevention for
      lung-cancer-cell proliferation.

PMID- 10209965
TI  - The multidrug resistance-associated protein (MRP) is over-expressed and
      functional in rat hepatoma cells.
AB  - Expression of multidrug-resistance-associated protein (MRP), a drug efflux pump
      transporting a wide range of xenobiotics, including anti-cancer drugs and
      chemical carcinogens, and present at low levels in normal hepatocytes, was
      investigated in rat hepatoma cells. Northern-blot analysis allowed detection of
      high levels of MRP mRNA in rat diethylnitrosamine-induced hepatocarcinomas when
      compared with normal liver. Similarly, elevated expression of MRP transcripts
      were evidenced in 6 rat hepatoma cell lines of different origins, especially in
      HTC cells, that, in contrast, failed to express mRNA of the canalicular
      multispecific organic anion transporter (cMOAT), an efflux pump sharing numerous
      substrates with MRP. HTC cells were also found by Western blotting to display
      much higher amounts of MRP than those observed in normal hepatocytes. In
      contrast, the MRP gene copy number was similar both in hepatoma HTC cells and in
      hepatocytes, as assessed by Southern blotting. Analysis of MRP-related transport
      using 3 types of MRP substrates, namely, the fluorescent glutathione-bimane, the
      anionic dye calcein and the cationic anti-cancer drug vincristine, demonstrated
      that HTC cells displayed cellular efflux of these 3 compounds, an efflux strongly
      inhibited by MRP modulators such as indomethacin. These results indicate that MRP
      is over-expressed and functional in rat hepatoma cells and may therefore be
      included in the de-toxifying pathways that are altered during
      hepatocarcinogenesis and are thus thought to contribute to the known multidrug
      resistance of liver tumors.

PMID- 10209966
TI  - Human melanoma therapy in the SCID mouse: in vivo targeting and reactivation of
      melanoma-specific cytotoxic T cells by bi-specific antibody fragments.
AB  - The adoptive transfer of tumor-specific cytotoxic T cells (CTL) offers a
      promising perspective in cancer immunotherapy. However, the ex vivo-generated T
      lymphocytes are mostly IL-2-dependent. Here we explored the possibility of
      circumventing the requirement for IL-2, known for severe side effects in the
      patient, and of simultaneously targeting the CTL towards the tumor by the use of
      2 bi-specific antibody fragments. As a model system, we used SCID mice bearing an
      s.c.-implanted human melanoma line (BLM-gp100) and in vitro-generated CTL
      specific for the gp100-derived immunogenic peptide YLEPGPVTA, which were injected
      i.v. with delay. To maintain the cytotoxic potential of the transferred CTL, 2 bi
      specific antibody (biAb) fragments were generated which bound with one arm either
      CD3 or CD28, a combination known to support the activation of CTL. For targeting
      the CTL, both biAbs contained the F(ab') part of HD-Me13, an antibody recognizing
      p97, a non-immunogenic melanoma-associated surface molecule. In vitro and in
      vivo, the addition of the 2 biAbs increased the cytotoxic potential of the gp100
      specific CTL and supported their clonal expansion in the absence of IL-2.
      Correspondingly, significantly higher numbers of CTL were recovered from melanoma
      bearing SCID-mice that received the 2 biAb than from mice treated with the CTL
      only. In animals treated with CTL plus both biAbs, the primary tumor did not
      grow, and none of the mice developed metastases. Thus, this set of bi-specific
      antibody fragments was proved to target effector cells in the tumor-bearing host
      and to efficiently support in vivo clonal expansion and cytolytic activity of in
      vitro-generated CTL.

PMID- 10209967
TI  - Novel and classical protein kinase C isoforms have different functions in
      proliferation, survival and differentiation of neuroblastoma cells.
AB  - To elucidate the possibility of utilizing protein kinase C (PKC) isoforms as
      target genes in neuroblastoma therapy, 5 neuroblastoma cell lines and
      neuroblastoma tumor specimens were examined for PKC isoform expression pattern
      and the cell lines were analyzed for sensitivity to PKC inhibition. All cell
      lines [IMR-32, LAN-2, LAN-5, SH-SY5Y and SK-N-BE(2)] expressed alpha, betaII,
      delta and epsilon isoforms of PKC, while no PKCeta or theta protein was detected
      in any cell line. PKCgamma was found only in LAN-2 cells. PKCalpha, betaII and
      delta were detected in 5 neuroblastoma tumors and PKCepsilon in 4 out of 5
      tumors. Exposure to the PKC inhibitors GF109203X, Go 6976 or Go 6983 caused a
      decrease whereas activation of PKC with 12-O-tetradecanoyl phorbol 13-acetate
      caused an increase in the number of neuroblastoma cells. The effect of Go 6976
      was due to both inhibited proliferation and to increased apoptosis. While
      GF109203X suppressed neurite outgrowth induced by a growth factor combination, Go
      6976 potentiated neurite outgrowth. Our data suggest a role for classical PKC
      isoforms in neuroblastoma growth and survival and for novel isoforms in neurite
      outgrowth.

PMID- 10209968
TI  - Maintaining vigilance over quality of EU research.

PMID- 10209969
TI  - Breast cancer: delays, dilemmas, and delusions.

PMID- 10209970
TI  - The fall and rise of sleeping sickness.

PMID- 10209971
TI  - What level of care for the neurofibromatoses?

PMID- 10209972
TI  - Total parenteral nutrition in the critically ill patient.

PMID- 10209973
TI  - Propofol-infusion syndrome in children.

PMID- 10209974
TI  - Influence of delay on survival in patients with breast cancer: a systematic
      review.
AB  - BACKGROUND: Most patients with breast cancer are detected after symptoms occur
      rather than through screening. The impact on survival of delays between the onset
      of symptoms and the start of treatment is controversial and cannot be studied in
      randomised controlled trials. We did a systematic review of observational studies
      (worldwide) of duration of symptoms and survival. METHODS: We identified 87
      studies (101,954 patients) with direct data linking delay (including delay by
      patients) and survival. We classified studies for analysis by type of data in the
      original reports: category I studies had actual 5-year survival data (38 studies,
      53,912 patients); category II used actuarial or multivariate analyses (21
      studies, 25,102 patients); and category III was all other types of data (28
      studies, 22,940 patients). We tested the main hypothesis that longer delays would
      be associated with lower survival, and a secondary hypothesis that longer delays
      were associated with more advanced stage, which would account for lower survival.
      FINDINGS: In category I studies, patients with delays of 3 months or more had 12%
      lower 5-year survival than those with shorter delays (odds ratio for death 1.47
      [95% CI 1.42-1.53]) and those with delays of 3-6 months had 7% lower survival
      than those with shorter delays (1.24 [1.17-1.30]). In category II, 13 of 14
      studies with unrestricted samples showed a significant adverse relation between
      longer delays and survival, whereas four of five studies of only patients with
      operable disease showed no significant relation. In category III, all three
      studies with unrestricted samples supported the primary hypothesis. The 13
      informative studies showed that longer delays were associated with more advanced
      stage. In studies that controlled for stage, longer delay was not associated with
      shorter survival when the effect of stage on survival was taken into account.
      INTERPRETATION: Delays of 3-6 months are associated with lower survival. These
      effects cannot be accounted for by lead-time bias. Efforts should be made to keep
      delays by patients and providers to a minimum.

PMID- 10209975
TI  - Factors predicting delayed presentation of symptomatic breast cancer: a
      systematic review.
AB  - BACKGROUND: Delayed presentation of symptomatic breast cancer is associated with
      lower survival. Understanding of the factors that influence delay is important
      for the development of strategies to shorten delays. We did a systematic review
      to assess the quality and strength of evidence on risk factors for delays by
      patients and providers. METHODS: We generated hypotheses about the relation
      between each putative risk factor and delay, against which we tested studies. We
      did searches to identify papers containing original data related to risk factors
      for delays by patients (n=86) and providers (n=28). We critically appraised the
      papers for inclusion in the review according to predefined criteria. The small
      number of studies of adequate quality did not allow formal meta-analysis. We
      therefore assigned strength of evidence according to a combination of the number
      and size of studies supporting, not supporting, or refuting the hypotheses.
      FINDINGS: Most studies were deemed to be of poor quality and were excluded. Among
      23 studies of adequate quality, however, there was strong evidence for an
      association between older age and delay by patients, and strong evidence that
      marital status was unrelated to delays by patients. Younger age and presentation
      with a breast symptom other than a lump were strong risk factors for delays by
      providers. Moderate evidence was shown for several other factors. INTERPRETATION:
      The strength of the current evidence is inadequate to inform the development of
      specific strategies to shorten delays by patients or providers. Clarification of
      the findings of this review through a major programme of primary research is
      urgently required.

PMID- 10209976
TI  - Effect on survival of delays in referral of patients with breast-cancer symptoms:
      a retrospective analysis.
AB  - BACKGROUND: From April 1, 1999, family physicians are required to refer all
      patients who have suspected breast cancer in the UK urgently to hospital, to be
      seen within 14 days of referral. We investigated whether delays by providers in
      routine practice for diagnosis influence survival. METHODS: We did a
      retrospective analysis of 36,222 patients with breast cancer listed in the
      Yorkshire Cancer Registry. Data on delay after family-physician referral,
      hospital visit, and start of treatment were available, as well as on tumour grade
      and stage of presentation. RESULTS: There was no evidence that provider delays of
      longer than 90 days adversely influenced survival. The time from family-physician
      referral to first hospital visit changed little (median 10 vs 13 days) from 1976
      to 1995, whereas time from first visit to first treatment doubled (7 vs 13 days).
      More than 8% of patients younger than 50 years delayed longer than 90 days,
      compared with 3% of patients older than 50 years (p<0.001). 48% of younger
      patients had their first treatment within 30 days compared with 64% of those
      older than 50 (p<0.001). The survival for 5708 patients diagnosed in 1986-90
      selected for survival analysis was 63% at 5 years, and 51% at 8 years. Patients
      who presented early and were treated in less than 30 days had significantly worse
      outcomes (p<0.001). INTERPRETATION: Delays by providers in diagnosis of 3 months
      or more do not seem to be associated with decreased survival in patients
      presenting with breast cancer. The drive for all women with possible breast
      cancer to be seen within 14 days will divert resources from other services and is
      not supported by this study.

PMID- 10209977
TI  - Efficacy of hepatitis A vaccine in prevention of secondary hepatitis A infection:
      a randomised trial.
AB  - BACKGROUND: Hepatitis A vaccination stops outbreaks of hepatitis A infection, but
      its efficacy against infection after exposure has not been proven. We
      investigated the use of hepatitis A vaccine to prevent secondary infections with
      hepatitis A virus (HAV). METHODS: We did a randomised controlled trial of
      hepatitis A vaccine in household contacts of people with sporadic HAV infection
      (index cases). Households (index cases and contacts) were randomly assigned to
      the vaccine group or unvaccinated group, according to the study week in which
      they were enrolled. All household contacts in the vaccine group received
      vaccination at the time of entry to the study. FINDINGS: During 45 days of follow
      up, secondary infection had occurred in ten (13.3%) of 75 households (two
      families had two cases each) in the untreated group and in two (2.8%) of 71
      households in the vaccine group. The protective efficacy of the vaccine was 79%
      (95% CI 7-95). The number of secondary infections among household contacts was 12
      (5.8%) of 207 in the unvaccinated group and two (1.0%) of 197 in the vaccinated
      group. Therefore, 18 individuals needed to be vaccinated to prevent one secondary
      infection. INTERPRETATION: Hepatitis A vaccine is effective in the prevention of
      secondary infection of HAV and should be recommended for household contacts of
      primary cases of HAV infection.

PMID- 10209979
TI  - Effect of mebendazole therapy during pregnancy on birth outcome.
AB  - BACKGROUND: In areas endemic for hookworm, routine antenatal mebendazole therapy
      could greatly reduce the prevalence of anaemia in pregnancy. At present, however,
      this is not a widely accepted control strategy because of a lack of data on the
      safety of the drug. We assessed the effect of mebendazole therapy during
      pregnancy on birth outcome. METHODS: A cross-sectional study was done in Sri
      Lanka, where prescription of mebendazole to women in the second trimester of
      pregnancy is recommended. Two hospitals were chosen for the study, and women who
      gave birth there between May, 1996, and March, 1997, were recruited. We compared
      the rates of major congenital defects, stillbirth, perinatal death, and low
      birthweight (< or = 1500 g) among babies of mothers who had taken mebendazole
      during pregnancy with those whose mothers had not taken an anthelmintic
      (controls). FINDINGS: The rate of major congenital defects was not significantly
      higher in the mebendazole group than in the control group (97 [1.8%] of 5275 vs
      26 [1.5%] of 1737; odds ratio 1.24 [95% CI 0.8-1.91], p=0.39). Among 407 women
      who had taken mebendazole in the first trimester (contrary to medical advice), 10
      (2.5%) had major congenital defects (odds ratio vs controls 1.66 [0.81-3.56],
      p=0.23). The proportions of stillbirths and perinatal deaths were significantly
      lower in the mebendazole group (1.9 vs 3.3%, 0.55 [95% CI 0.4-0.77]), as was the
      proportion of low-birthweight babies (1.1 vs 2.3%, 0.47 [95% CI 0.32-0.71]).
      INTERPRETATION: Mebendazole therapy during pregnancy is not associated with a
      significant increase in major congenital defects, but our results indicate that
      it should be avoided during the first trimester. This therapy could offer
      beneficial effects to pregnant women in developing countries, where intestinal
      helminthiases are endemic.

PMID- 10209978
TI  - Environmental exposure to cadmium, forearm bone density, and risk of fractures:
      prospective population study. Public Health and Environmental Exposure to Cadmium
      (PheeCad) Study Group.
AB  - BACKGROUND: Chronic low-level exposure to cadmium may promote calcium loss via
      urinary excretion. We undertook a prospective population study to investigate
      whether environmental exposure to cadmium lowers bone density and increases risk
      of fractures. METHODS: We measured urinary cadmium excretion, a biomarker of
      lifetime exposure, in people from ten districts of Belgium, of which six
      districts bordered on three zinc smelters. We also measured cadmium in soil and
      in vegetables from the districts, and collected data on incidence of fractures
      and height loss. Bone density was measured at the forearm just above the wrist by
      single photon absorptiometry, and calculated as the mean of six proximal and four
      distal scans. FINDINGS: Mean cadmium excretion at baseline was 8.7 nmol daily.
      Across the ten districts, mean cadmium concentration in soil ranged from 0.8 to
      14.7 mg/kg, and from 0.1 to 4.0 mg/kg dry weight in vegetables. Median follow-up
      was 6.6 years. Mean forearm bone density in proximal and distal scans was 0.54
      g/cm2 and 0.43 g/cm2 in men, and 0.44 g/cm2 and 0.34 g/cm2 in women. In
      postmenopausal women, a twofold increase in urinary cadmium correlated with 0.01
      g/cm2 decrease in bone density (p<0.02). The relative risks associated with
      doubled urinary cadmium were 1.73 (95% CI 1.16-2.57; p=0.007) for fractures in
      women and 1.60 (0.94-2.72, p=0.08) for height loss in men. Cadmium excretion in
      districts near smelters was 22.8% higher (p=0.001) than in other districts, with
      fracture rates of 16.0 and 10.3 cases per 1000 person-years, respectively, and a
      population-attributable risk of 35.0%. INTERPRETATION: Even at a low degree of
      environmental exposure, cadmium may promote skeletal demineralisation, which may
      lead to increased bone fragility and raised risk of fractures.

PMID- 10209980
TI  - Rapidly progressive dementia.

PMID- 10209981
TI  - Mothering skills and health in infancy: the Thousand Families study revisited.

PMID- 10209982
TI  - The mother-infant relationship: who controls breastfeeding frequency? Euro-Growth
      Study Group.

PMID- 10209983
TI  - Medulloblastomas and the human neurotropic polyomavirus JC virus.

PMID- 10209984
TI  - Methanol/acetone treatment helps the amplification of FMR1 CGG repeat fragment in
      dried blood spots from Guthrie cards.

PMID- 10209985
TI  - Sham continuous positive airway pressure for placebo-controlled studies in sleep
      apnoea.

PMID- 10209986
TI  - Treatment of central pontine myelinolysis with therapeutic plasmapheresis.

PMID- 10209987
TI  - Towards enzyme-replacement treatment in triosephosphate isomerase deficiency.

PMID- 10209988
TI  - MTHFR gene polymorphism and diabetic nephropathy in type 1 diabetes.

PMID- 10209989
TI  - Amantadine and pneumonia.

PMID- 10209991
TI  - Homelessness and psychiatric admission rates through the criminal justice system.

PMID- 10209990
TI  - Under-reporting of antibiotic anaphylaxis may put patients at risk.

PMID- 10209992
TI  - To be realistic or stick one's head in the sand?

PMID- 10209993
TI  - Labour's health reforms begin.

PMID- 10209994
TI  - Compulsory drug licensing for countries hit by HIV is mooted.

PMID- 10209995
TI  - Venous thrombosis: a multicausal disease.
AB  - The risk factors for venous thrombosis differ from those for arterial vascular
      disease. During the past 5 years, knowledge about the aetiology of venous
      thrombosis has advanced with the discovery of several factors that contribute to
      the incidence of thrombosis, particularly the role of coagulation abnormalities.
      These abnormalities are common in the general population and therefore will be
      present simultaneously in some individuals. The resultant gene-gene and gene
      environment interactions between risk factors are the key to the understanding of
      why a certain person develops thrombosis at a specific point in time.

PMID- 10209996
TI  - The performance of doctors: the new professionalism.

PMID- 10209997
TI  - The role and education of doctors in the delivery of health care.

PMID- 10209998
TI  - Is there a Gulf War syndrome?

PMID- 10209999
TI  - Is there a Gulf War syndrome?

PMID- 10210000
TI  - Is there a Gulf War syndrome?

PMID- 10210001
TI  - Is there a Gulf War syndrome?

PMID- 10210002
TI  - Calcium antagonist and prevention of dementia in elderly people.

PMID- 10210003
TI  - Is flutamide effective in patients with bilateral orchiectomy?

PMID- 10210004
TI  - Social noise and hearing loss.

PMID- 10210006
TI  - Issues in rheumatoid arthritis.

PMID- 10210005
TI  - Thrombocytopenia and glycoprotein IIb-IIIa receptor antagonists.

PMID- 10210007
TI  - Issues in rheumatoid arthritis.

PMID- 10210008
TI  - Male breast cancer: risk to daughters.

PMID- 10210009
TI  - Periconceptional folic acid intake in the northern Netherlands.

PMID- 10210010
TI  - Allergen-specific T-cell memory.

PMID- 10210011
TI  - Child obesity and body-mass index.

PMID- 10210012
TI  - Dendritic cell immuno-therapy in disseminated parathyroid carcinoma.

PMID- 10210013
TI  - Hyperosmolar coma.

PMID- 10210014
TI  - Coeliac disease in Saharawi children in Algerian refugee camps.

PMID- 10210015
TI  - Resistance to vancomycin in US chicken feed.

PMID- 10210016
TI  - Encouraging high-quality clinical research in the tropics.

PMID- 10210017
TI  - Timely publication of critical letters.

PMID- 10210018
TI  - Increased efficiency in use of laboratory animals.

PMID- 10210019
TI  - European Commission funding of research.

PMID- 10210020
TI  - Safe cycling.

PMID- 10210021
TI  - The Nobel chronicles. 1948: Paul Hermann Muller (1899-1965)

PMID- 10210022
TI  - Prospective follow-up of intellectual development in children with a recent onset
      of epilepsy.
AB  - In this study the intellectual development of children with a recent onset of
      epilepsy was compared to that of children without epilepsy. Eleven children aged
      7-15 years and with mean duration of epilepsy of 2 years and 38 children without
      epilepsy performed three times the dutch Wechsler intelligence scale for children
      revised and the Beery developmental test for visuo-motor integration. The
      children with epilepsy did show a significantly less gain in FSIQ score over the
      11 years of follow-up. Performance intelligence scores and Beery standardized
      scores showed a trend towards this effect. Findings partly support the
      hypothesized cascadic model of deterioration, in which children with epilepsy are
      supposed to show a process of mental deterioration shortly after the onset of
      epilepsy. The lack of evidence of an absolute mental deterioration are discussed
      in terms of methodology, mental age and premorbid intelligence level.

PMID- 10210023
TI  - The efficacy of felbamate as add-on therapy to valproic acid in the Lennox
      Gastaut syndrome.
AB  - We studied the efficacy of felbamate (FBM) in combination with valproic acid
      (VPA) in 13 patients with the Lennox-Gastaut syndrome and evaluated the
      contribution of each drug. Following stabilization on VPA monotherapy, FBM or
      placebo titration was performed for two observation periods lasting 7 weeks with
      a washout period between them. 6-h video-electroencephalography was recorded
      following each observation period. In addition to examining the effects of the
      drugs with parental reports and video-EEG, we compared video-EEG data with
      families' seizure reports. Based on parental counts for the 7-week observation
      periods, patients had 40% fewer drop attacks (p < 0.03, Wilcoxon rank sum test)
      and 60% fewer total seizures (p < 0.02) on VPA and FBM. VPA level rose by 12.7%
      when FBM was added (p < 0.01). When the effect of FBM was factored out, VPA had a
      significant effect on drop attack frequency, although not total number of
      seizures. FBM's therapeutic effect on drop attacks is due in part to increased
      VPA levels, although the combination may be synergistic for the effect on total
      seizure number.

PMID- 10210024
TI  - The course of untreated seizures in the pilocarpine model of epilepsy.
AB  - The course of untreated epilepsy is not well established. This study uses a model
      of chronic limbic epilepsy (pilocarpine model of epilepsy) to determine the
      pattern of occurrence of seizures in untreated animals. Following pilocarpine
      administration, 21 rats were monitored continuously with a video system for 135
      days after the first spontaneous seizure. Animals showed a great variability in
      seizure numbers and were divided in two subgroups presenting either a low
      frequency of seizures (n = 9 animals presenting ten or less seizures in the first
      15 days of observation) or a high frequency of seizures (n = 12 animals
      presenting more than ten seizures during this period). Animals with low number of
      seizures during the first 15 days of observation showed a significant increase in
      seizure frequency in the following period of analysis (until 105 days). On the
      other hand, those with initial high number of seizures showed significant changes
      in seizure frequency only in the first 2 months. The duration of each spontaneous
      seizure did not change significantly over time. These findings show that in
      untreated epilepsy there is a maturation process in the early stages and this
      accelerating process can be of predictive value for the treatment of epilepsy.

PMID- 10210025
TI  - Clinical aspects and biological bases of drug-resistant epilepsies.
AB  - The definition of drug-resistant epilepsy (DRE) is elusive and still
      controversial owing to some unresolved questions such as: how many drugs should
      be tried before a patient is considered intractable; to which extent side-effects
      may be acceptable; how many years are necessary before establishing drug
      resistance. In some cases, the view of epilepsy as a progressive disorder
      constitutes another important issue. Despite the use of new antiepileptic drugs
      (AEDs), intractable epilepsy represents about 20-30% of all cases, probably due
      to the multiple pathogenetic mechanisms underlying refractoriness. Several risk
      factors for pharmacoresistance are well known, even if the list of clinical
      features and biological factors currently accepted to be associated with
      difficult-to-treat epilepsy is presumably incomplete and, perhaps, disputable.
      For some of these factors, the biological basis may be common, mainly represented
      by mesial temporal sclerosis or by the presence of focal lesions. In other cases,
      microdysgenesis or dysplastic cortex, with abnormalities in the morphology and
      distribution of local-circuit (inhibitory) neurons, may be responsible for the
      severity of seizures. The possible influence of genes in conditioning inadequate
      intraparenchimal drug concentration, and the role of some cytokines determining
      an increase in intracellular calcium levels or an excessive growth of distrophic
      neurites, constitute other possible mechanisms of resistance. Several hypotheses
      on the mechanisms involved in the generation of DRE have been indicated: (a)
      ontogenic abnormalities in brain maturation; (b) epilepsy-induced alterations in
      network, neuronal, and glial properties in seizure-prone regions such as the
      hippocampus; (c) kindling phenomenon; (d) reorganization of cortical tissue in
      response to seizure-induced disturbances in oxygen supply. Such hypotheses need
      to be confirmed with suitable experimental models of intractable epilepsy that
      are specifically dedicated, which have until now been lacking.

PMID- 10210026
TI  - Life-long history of injuries related to seizures.
AB  - There is meager information in the literature regarding the characteristics and
      risk factors for injuries caused during epileptic seizures in adults. Previous
      studies focused mainly on specific types of injuries incurred, and only few
      explored associated risk factors. A questionnaire regarding lifetime seizures and
      their traumatic consequences was administered to 298 consecutive epileptic
      patients and their caretakers or relatives. Ninety-one of them (30%) have
      reported trauma: 185 events (age 39.8+/-18 years, 54 males), of which 61 were
      severe. This translates to one seizure-related injury every 21 patient-years, and
      a serious injury once every 64 patient-years. The most common site of injury was
      the head (55% of the events). Blunt injuries occurred most frequently (40%),
      followed by cuts (28%). Severe injuries included fractures and dislocations
      (17%), burns (6%), brain concussion (6%), subdural hematoma (3%) and
      intracerebral hematoma (1%). Most injuries occurred at home. The 91 patients with
      traumatic events were compared with the 207 epileptic patients without previous
      trauma (age 37.8+/-14.7 years, 112 males). Patients with seizure-related trauma
      had significantly earlier onset age of epilepsy. They more commonly had
      generalized from onset tonic-clonic, complex partial, myoclonic or absence
      seizures but fewer had partial seizures with secondary generalization. The risk
      of trauma was mostly related to seizure type (generalized tonic clonic from onset
      and myoclonic seizures). This information may be helpful for better management of
      epileptic patients.

PMID- 10210027
TI  - Phenytoin pharmacokinetics following oral administration of phenytoin suspension
      and fosphenytoin solution to rats.
AB  - The administration of phenytoin suspension in conjunction with enteral nutrition
      supplements through nasogastric (NG) feeding tubes to humans has been associated
      with suboptimal phenytoin absorption, subtherapeutic concentrations, and
      breakthrough seizures. Postulated mechanisms include chelation to proteins and
      electrolytes in the enteral feeding, binding to NG tubing, and alterations in
      gastrointestinal pH resulting in precipitation of phenytoin. The purpose of this
      pilot study was to evaluate the oral absorption of commercially available
      fosphenytoin injectable solution compared to phenytoin suspension in the rat to
      determine whether equivalent oral fosphenytoin and phenytoin suspension doses
      should be used for future human studies of fosphenytoin oral absorption in the
      presence of concomitant enteral nutrition. A single oral 30 mg/kg phenytoin
      equivalents dose of either commercially available fosphenytoin or phenytoin
      suspension was administered to male Wistar rats following an overnight fast.
      Blood samples (0.3 ml) for phenytoin plasma concentration were obtained from a
      jugular vein catheter at baseline and 0.5, 1, 1.5, 2, 3, 4, 5, 8, 12 and 24 h
      post-study drug administration and analyzed by high performance liquid
      chromatography (HPLC) (CV% < 6). Mean phenytoin Cmax was 85% [corrected] (P =
      0.010) higher in fosphenytoin vs phenytoin treated rats. Tmax was 2.4 h (62%,
      P=0.021) shorter in fosphenytoin vs phenytoin treated rats. No significant
      differences in AUClast were found. The presence of a phosphate ester moiety does
      not appear to inhibit the appearance of phenytoin following oral administration
      of fosphenytoin. Phenytoin plasma concentration profiles following oral
      administration of fosphenytoin are characterized by higher Cmax and shorter Tmax
      values relative to oral administration of phenytoin suspension.

PMID- 10210028
TI  - Epilepsy and seizure occurrence in a population-based sample of Virginian twins
      and their families.
AB  - Epilepsy and seizure occurrence was assessed in a large, population-based sample
      of Virginian twins and their families. Medical history information on twins and
      their relatives was collected by questionnaire and used to estimate prevalence of
      seizures and epilepsy for this sample. Health history information was available
      on 16,634 twins and their families. Lifetime prevalence of a history of seizures
      ranged from < 1 to 5%. Concordance rates were larger in monozygotic (MZ) than
      dizygotic (DZ) pairs overall, however, significant differences between the
      zygosities were only noted for Caucasian twins. To facilitate interpretation of
      results, the sample was partitioned into two age groups: 16-35 years and > 35
      years of age. In the first age category of twins, significant differences were
      observed for the following seizure types; epilepsy (0.30 and 0.13, p <0.03),
      febrile seizures (0.39 and 0.12, p <0.001), and other convulsions/seizures (0.28
      and 0.01, p < 0.001). While for twins in the second age category, only the
      comparison for febrile seizures (0.42 and 0.14, p < 0.001) resulted in a
      significant difference between zygosities. A family history of seizures was
      reported in 215 (35.1%) of the 613 seizure positive probands. Increased risk of
      seizures (1.88-4.64) among relatives of affected versus unaffected individuals
      was also observed.

PMID- 10210029
TI  - Changes in plasma GABA concentration during vigabatrin treatment of epilepsy: a
      prospective study.
AB  - The aim of the present prospective study was to evaluate changes in plasma GABA
      concentration in relation to clinical response during vigabatrin treatment of
      epilepsy. We studied 29 patients with uncontrolled partial-onset seizures during
      open add-on vigabatrin treatment and measured plasma GABA and vigabatrin
      concentrations by a sensitive HPLC method. Following short-term treatment 17 out
      of 28 patients had a seizure reduction of > 50% (responders). After long-term
      treatment 16 out of 22 patients were responders. There was no difference between
      responders and nonresponders regarding pretreatment seizure frequency, treatment
      duration, vigabatrin dose, or plasma vigabatrin concentration. Responders had a
      significant (p < 0.001) increase in mean plasma GABA both after short-term (from
      0.380 to 0.530 nmol/ml; mean increase: 48%) and after long-term (from 0.392 to
      0.618 nmol/ml; mean increase: 71%) vigabatrin treatment, whilst nonresponders had
      no significant changes in GABA levels. However, since plasma GABA increased in a
      subgroup of nonresponders, mean plasma GABA levels did not differ between
      responders and nonresponders. Although plasma GABA increased significantly in the
      responder but not in the nonresponder group during vigabatrin treatment of
      patients with epilepsy, it does not seem to be a reliable marker of individual
      clinical response to vigabatrin treatment.

PMID- 10210030
TI  - Alternate-site kindling in the guinea-pig results in accelerated seizure
      progression and generalization.
AB  - In rats, the concurrent alternate elicitation of epileptiform activity in two
      forebrain structures can result in both the rapid production of severe seizures
      and the development of fully generalized seizures in one (dominant) site, while
      arresting the progress of seizure activity at intermediate stages in the other
      (suppressed) site. The latter phenomenon is known as kindling antagonism. In this
      study, we examined alternate-site kindling in the guinea-pig as they fail to
      express fully generalized (stage 5) convulsions during single-site kindling. We
      assessed both seizure stage and afterdischarge duration following inter
      hemispheric alternate-site kindling stimulation of the amygdala and medial septal
      areas. Alternating-site kindling of the medial septal and amygdaloid areas
      bypassed the normal inhibitory mechanisms in some guinea-pigs, enabling them to
      reach a stage 5 seizure. Furthermore, alternate-site kindled guinea-pigs
      demonstrated three (absolute, relative, and mutual) types of kindling antagonism.
      Guinea-pig kindling as a model of human partial epilepsy is discussed.

PMID- 10210031
TI  - Blood and cerebrospinal fluid pharmacokinetics of the novel anticonvulsant
      levetiracetam (ucb L059) in the rat.
AB  - The temporal pharmacokinetic interrelationship of levetiracetam in blood and
      cerebrospinal fluid (CSF) was studied after acute intraperitoneal administration
      of levetiracetam (20, 40 and 80 mg/kg), using an animal model that permits
      concurrent blood and CSF sampling in freely moving rats. After administration,
      levetiracetam rapidly appeared in both serum (time to maximum concentration
      (Tmax) mean range 0.25 0.50 h) and CSF (Tmax mean range 1.33-1.92 h), suggesting
      ready penetration of the blood brain barrier. Both serum and CSF levetiracetam
      concentrations rose essentially linearly and dose-dependently, suggesting that
      transport across the blood-brain barrier is not rate limiting over the
      levetiracetam concentration range observed in the present study. However, while
      apparent elimination half-life (t1/2) values for both serum and CSF were dose
      independent (mean value range 1.8-2.8 and 4.4-4.9 h, respectively), t1/2 values
      for CSF were significantly larger. As the serum free/total serum levetiracetam
      concentration ratio (free fraction) was 1.01+/-0.02 (mean+/-S.E.M.), it can be
      concluded that levetiracetam is not protein bound. Furthermore, the free fraction
      was indistinguishable from that of the CSF/serum levetiracetam concentration
      ratio at equilibrium. It can be concluded that the kinetics of levetiracetam, in
      the rat, is simple and, thus, dosing strategies in studies designed to elucidate
      its mechanism of action should be straightforward.

PMID- 10210032
TI  - Kindled seizures activate both branches of the autonomic nervous system.
AB  - Amygdaloid kindled seizures in the rat induce an abrupt elevation of blood
      pressure accompanied by a significant decrease in heart rate. The autonomic
      pharmacology of this response was examined in unanesthetized kindled rats.
      Muscarinic receptor blockade with atropine (1 mg/kg, intravenous (i.v.))
      abolished the seizure-induced bradycardia. The seizure-induced hypertension was
      unaffected by beta-adrenergic blockade with timolol (1 mg/kg, i.v.), but was
      reduced by phentolamine (5 mg/kg, subcutaneous (s.c.)), an alpha-adrenergic
      receptor antagonist. A chemical sympathectomy was induced with 6-hydroxydopamine
      (100 mg/kg, i.v.), an agent that does not cross the blood-brain barrier. This
      eliminated the pressor response but did not completely block the seizure-induced
      bradycardia. The effectiveness of 6-hydroxydopamine was tested with tyramine (0.5
      mg/kg, i.v.) an agent that releases endogenous catecholamines. These results
      indicate amygdaloid kindled seizures activate both branches of the autonomic
      nervous system. The bradycardia was mediated by the parasympathetic system; the
      pressor response was caused by an increase in peripheral resistance due to alpha
      adrenergic receptor activation. More important, these findings show that kindling
      is a useful seizure model for future studies on the effect of seizures on
      cardiovascular function and possible mechanisms of seizure-related sudden
      unexplained death.

PMID- 10210033
TI  - Induction of seizures by the potent K+ channel-blocking scorpion venom peptide
      toxins tityustoxin-K(alpha) and pandinustoxin-K(alpha).
AB  - The scorpion venom peptide toxins tityustoxin-K(alpha) (TsTx-K(alpha)) and
      pandinustoxin-K(alpha) (PiTx-K(alpha)) are novel, highly potent and selective
      blockers of voltage-activated K+ channels. PiTx-K(alpha) preferentially blocks
      rapidly inactivating (A-type) K+ channels whereas TsTx-K(alpha) is selective for
      slowly inactivating (delayed rectifier-type) channels. K+ channel blockers are
      known to induce seizures, but the specific K channel types that can serve as
      convulsant targets are not well defined. To address this issue, we examined for
      convulsant activity the K+ channel type-specific scorpion toxins and the
      selective K+ channel antagonists 4-aminopyridine (4-AP), an inhibitor of A-type
      voltage-activated K+ channels, and paxilline, a selective blocker of large
      conductance (maxi K) Ca(2+)-activated K+ channels. Intracerebroventricular
      injection of recombinant TsTx-K(alpha) and PiTx-K(alpha) in mice produced limbic
      and clonic-tonic seizures. The severity of the seizures increased during the 60
      min period following injection, culminating in continuous clonic seizure activity
      (status epilepticus), tonic hindlimb extension, and eventually in death. The
      estimated doses producing limbic and clonic seizures in 50% of animals (CD50) for
      TsTx-K(alpha) and PiTx-K(alpha) were 9 and 33 ng, respectively. 4-AP produced
      seizure activity similar to the toxins (CD50, 76 ng) whereas paxilline failed to
      induce seizures at doses up to 13.5 microg. Carbamazepine protected fully against
      the toxin- and 4-AP-induced seizures whereas phenytoin had variable activity
      against the clonic component although it was protective against tonic hindlimb
      extension. The AMPA receptor antagonist GYKI 52466 also conferred full protection
      against toxin-induced seizures, but the NMDA receptor antagonists (R)-CPP and
      dizocilpine failed to affect limbic and clonic seizures, although they protected
      against hindlimb extension. We conclude that selective blockade of delayed
      rectifier- or A-type voltage-activated K+ channels can produce limbic, clonic and
      tonic seizures, whereas blockade of maxi K-type Ca(2+)-activated K+ channels does
      not. The convulsant effects may be related to enhanced glutamate release and, in
      the case of the limbic and clonic convulsions, activation of AMPA receptors.

PMID- 10210035
TI  - Double-blind substitution of vigabatrin and valproate in carbamazepine-resistant
      partial epilepsy. 012 Study group.
AB  - Patients from 12 countries reporting two or more partial seizures per month
      despite treatment with optimal doses of CBZ were randomised to additional
      vigabatrin (VGB, 2-4 g daily) or sodium valproate (VPA, 1-2 g daily) using a
      double-blind, double-dummy design. The study included a 6 month retrospective
      baseline on unchanged CBZ dosage, a month's prospective baseline, a short
      titration phase, and an assessment period lasting 3 months on duotherapy. CBZ was
      withdrawn over a further 2 months in responders ( > or = 50% monthly seizure
      reduction compared with baseline), who continued on alternative monotherapy for 3
      or more months. If seizure control deteriorated, CBZ was reinstated and these
      patients were also followed up for 3 months. A total of 215 patients (108 VGB,
      107 VPA) reporting a mean of seven partial seizures per month fulfilled the
      criteria for the intention-to-treat analysis. 53 and 51% of patients in the VGB
      and VPA group respectively achieved a monthly reduction in seizure numbers > or =
      50%, respectively. 27 and 31% maintained alternative monotherapy. Overall, 17%
      (7% monotherapy, 10% duotherapy) of the VGB treated patients and 19% (8%
      monotherapy, 11% duotherapy) of the VPA group remained seizure-free during the
      final 3 month treatment period. VGB and VPA, which increase neuronal inhibition
      mediated by gamma aminobutyric acid, can be added to or substituted for CBZ when
      this Na+ channel blocker fails to control partial seizures. This lends credence
      to the hypothesis in support of a mechanistic approach to the management of
      epilepsy.

PMID- 10210034
TI  - Biphasic effects of zonisamide on serotonergic system in rat hippocampus.
AB  - To study the mechanisms of antiepileptic action of zonisamide (ZNS), we
      determined the effects of ZNS on extracellular, total levels and re-uptake
      activity of serotonin (5-HT) in rat striatum and hippocampus. After acute
      administrations, plasma ZNS concentrations associated with anticonvulsive action
      (effective concentrations) increased the total levels of 5-HT, its metabolise (5
      hydroxyindoleacetic acid: 5-HIAA) and precursor (5-hydroxytryptophan: 5-HTP).
      After chronic administration of ZNS, effective plasma concentrations also
      increased the extracellular and total levels of 5-HT, 5-HIAA, and 5-HTP. On the
      other hand, after both acute and chronic administrations of ZNS, a supra
      effective ZNS concentration either decreased or did not affect the total levels
      of these substances. Therefore, the stimulatory effects of ZNS on the 5-HT system
      were reduced by an increase in ZNS concentration to supra-effective
      concentrations. ZNS concentrations of 30-1000 microM did not affect hippocampal
      5HT re uptake activity in vitro. These results suggest that ZNS has biphasic
      effects on the 5-HT system, in that effective concentrations of ZNS enhance and
      supra-effective concentrations of ZNS reduce the function of the 5-HT system.
      These biphasic effects of ZNS on the 5-HT system may be involved in the
      mechanisms of action of the antiepileptic and psychotropic effects, and side
      effects of ZNS.

PMID- 10210036
TI  - The structural requirements for the design of antiepileptic-glycine derivatives.
AB  - Glycine is a major inhibitory neurotransmitter and recent reports have shown that
      certain lipophilic derivatives of glycine demonstrate anticonvulsant activity in
      intact animals. In these studies, glycinamide derivatives were found to be more
      potent than their corresponding glycine analogues. Consequently, the objective of
      the current study was to investigate the pharmacokinetics and pharmacodynamics
      (anticonvulsant activity and neurotoxicity) of the following phenyl derivatives
      of glycinamide: N'-benzyl glycinamide, N-benzyloxycarbonyl glycinamide (Z
      glycinamide), Z-glycine, N-Z,N'-benzyl glycinamide and N-phenylacetyl
      glycinamide. The antiepileptic activity and neurotoxicity was carried out in
      classical animal models for antiepileptic screening. The pharmacokinetics of the
      active compounds were studied in dogs, a common animal model for comparative
      crossover pharmacokinetic studies. Of the compounds investigated in this study, Z
      glycinamide, N'-benzyl glycinamide and N-Z,N'-benzyl glycinamide were found to be
      active. Therefore, the disposition of Z-glycinamide and N-Z,N'-benzyl glycinamide
      in comparison to Z-glycine was studied in plasma, brain, liver and urine of rats.
      The disposition of Z-glycinamide and N-Z,N'-benzyl glycinamide into the brain was
      better than that of Z-glycine. Unlike glycine or glycinamide, Z-glycinamide and N
      Z,N'-benzyl glycinamide showed antiepileptic activity in animal models due to
      their better pharmacodynamic and pharmacokinetic properties. The pharmacokinetics
      of Z-glycinamide was similar in dogs and rats. Substitution of the Z group with
      the analogous phenylacetyl moiety led to inactive compounds. In an analogous
      series of compounds, the loss of the anticonvulsant activity may be due to
      pharmacodynamic and pharmacokinetic reasons. This study provides certain clues
      concerning the structural requirements for the design of antiepileptic-active
      glycine derivatives.

PMID- 10210037
TI  - Plasma amino acids in childhood epileptic encephalopathies.
AB  - Abnormalities in plasma amino acid levels have been noted in patients with
      various epilepsies, and sometimes also in their first degree relatives. We sought
      to study plasma amino acid levels in children with epileptic encephalopathies and
      their parents, relating findings to the pattern of cortical glucose metabolism as
      determined by 18fluorodeoxyglucose (FDG) positron emission tomography (PET).
      Twenty-eight children with cryptogenic epileptic encephalopathies were studied
      prospectively. Cortical glucose metabolism was evaluated by FDG PET with combined
      visual and semiquantitative analysis used to detect focal cortical defects. The
      plasma concentration of 21 amino acids in the children and their parents was
      measured by ion exchange chromatography and compared with control values using
      non-parametric statistical methods. Multivariate analysis was used to assess
      antiepileptic drug effects. Children were classified as: Lennox-Gastaut syndrome
      following infantile spasms (six patients); de-novo Lennox-Gastaut syndrome
      (eight); severe myoclonic epilepsy in infancy (eight) and myoclonic-astatic
      epilepsy (two). Four patients remained unclassified. Fourteen patients had
      focal/multifocal abnormalities on PET scans. The plasma level of aspartate was
      significantly lower in both the children with epileptic encephalopathies and in
      their parents (P < 0.005). The lowered aspartate levels could not be accounted
      for by the antiepileptic drug medication taken by the children. Further analysis
      showed the lowered aspartate levels to be confined to children and their parents
      who lacked focal PET abnormalities. These findings suggest a possible genetic
      abnormality in the aspartate neurotransmitter systems in the pathogenesis of
      seizures in the childhood epileptic encephalopathies.

PMID- 10210038
TI  - Cardiovascular effects of intracerebroventricular bicuculline in rats with
      absence seizures.
AB  - Gamma-aminobutyric acid (GABA) plays an important role in both central
      cardiovascular homeostasis and pathogenesis of epileptic seizures. Previous
      studies have indicated a critical role of the amygdala in the spread of seizures
      from brainstem to forebrain and in the regulation of autonomic responses such as
      blood pressure and heart rate. The purpose of the present study was to examine
      blood pressure and heart rate effects of bicuculline, a GABA(A) antagonist, and
      the effect of lesions of the central or the basolateral nuclei of the amygdala on
      bicuculline-induced cardiovascular responses in conscious WAG/Rij rats with
      absence epilepsy. Intracerebroventricular administration of 0.3 and 0.5 nmol of
      bicuculline produces an increase in blood pressure and a slight bradycardia in
      non-epileptic Wistar rats. The blood pressure response to intracerebroventricular
      bicuculline is significantly potentiated in epileptic WAG/Rij rats. Bilateral
      lesions of the basolateral nucleus of the amygdala of WAG/Rij rats completely
      prevent the pressor response to 0.5 nmol of bicuculline, whereas unilateral
      lesion of the basolateral nucleus does not affect blood pressure changes in
      epileptic WAG/Rij rats. Additionally, the pressor effect of 0.5 nmol of
      bicuculline is not attenuated by bilateral electrolytic ablation of the central
      nucleus of the amygdala in WAG/Rij rats. Heart rate response to bicuculline is
      not significantly changed in the lesioned groups. These findings indicate (a)
      altered GABAergic function in blood pressure regulation; and (b) a critical role
      of the basolateral nucleus in GABA(A)-mediated blood pressure control in
      epileptic WAG/Rij rats.

PMID- 10210039
TI  - Stress and avoidance in Pseudoseizures: testing the assumptions.
AB  - Twenty women and 10 men with Pseudoseizures were matched by age and gender with
      an epilepsy- and a healthy-control group. In response to clinical and research
      evidence of a relationship between Pseudoseizures and the experience of stress,
      it was hypothesised that people with Pseudoseizures would perceive their ongoing
      lives as more stressful, and use more avoidant and distancing coping, and less
      problem-focused coping, than people in the two control groups. Using the
      Perceived Stress Scale (Cohen et al., J. Health Soc. Behav. 24, 1983, 385-396)
      and the Ways of Coping, revised version (Folkman and Lazarus, Manual for Ways of
      Coping Questionnaire, Consulting Psychologist Press, Paola Alto, CA, 1988) the
      study found that people with Pseudoseizures: (1) perceived their ongoing lives as
      significantly more stressful; (2) were significantly more likely to use a
      maladaptive (escape-avoidant) coping strategy; and (3) were significantly less
      likely to use an adaptive (planful problem solving) approach to coping than
      healthy controls. The study findings indicate that people with Pseudoseizures
      experience lives as stressful as do people with epilepsy, and are likely to
      employ maladaptive coping responses. Implications for diagnosis, intervention and
      future research are discussed.

PMID- 10210040
TI  - Neuroprotective effect of remacemide hydrochloride in a perforant pathway
      stimulation model of status epilepticus in the rat.
AB  - Previous studies have demonstrated that remacemide and its desglycinyl
      metabolite, AR-R 2495AA, reduce neuronal damage in animal models of ischemia,
      subarachnoid hemorrhage, and traumatic brain injury. The aim of the present study
      was to investigate whether remacemide hydrochloride also alleviates seizure
      induced neuronal damage in a model of status epilepticus induced by the
      stimulation of the perforant pathway (PP) in the rat. Chronic oral remacemide
      treatment (3 x 25 mg/kg/day) was started either 2 days before or 2 h after the
      beginning of PP stimulation (2 mA, 20 Hz, 0.1 ms pulse duration for 60 min). The
      effects of remacemide treatment on the severity of seizures, electroencephalogram
      (EEG) parameters, seizure-induced neuronal damage in the temporal lobe regions,
      and memory impairment were compared to unstimulated and stimulated vehicle
      treated controls, and carbamazepine-pre-treated (3 x 40 mg/kg/day) rats. Both
      remacemide and carbamazepine pretreatments, but not remacemide posttreatment,
      decreased pyramidal cell damage in the CA3 and CA1 subregions of the hippocampus
      (P < 0.05). In addition, overall neuronal damage in the extrahippocampal temporal
      lobe regions (the piriform cortex, entorhinal cortex, and the amygdaloid complex)
      was milder in remacemide-pretreated rats compared to stimulated control rats (P <
      0.01). The neuroprotective effect was most evident on the side contralateral to
      stimulation. Remacemide or carbamazepine pretreatment had no evident effect on
      the number or duration of behavioral seizures during PP stimulation. Neither drug
      altered the spectral parameters of the baseline EEG or prevented status
      epilepticus-induced EEG slowing observed 2 weeks after PP stimulation. Nor did
      remacemide or carbamazepine treatment alleviate spatial memory impairment
      determined in a Morris water-maze task 2 weeks after PP stimulation. Our data
      provide evidence that pretreatment with remacemide has a moderate neuroprotective
      effect against status epilepticus-induced neuronal damage.

PMID- 10210041
TI  - Anesthesia of the upper airway.

PMID- 10210042
TI  - Continuous interscalene brachial plexus block.

PMID- 10210043
TI  - Anesthesia of the airway by aspiration of lidocaine.
AB  - PURPOSE: Lidocaine instilled onto to the back of the tongue of a supine subject
      and aspirated has been reported to provide effective topical anesthesia of the
      airway. The purpose of this study was to observe endoscopically the fate of
      lidocaine so instilled and document the efficacy of anesthesia for awake
      fibreoptic intubation. METHODS: In Part I of the study, a fibreoptic bronchoscope
      was positioned in the pharynx of three volunteers lying supine and the route
      followed by tinted lidocaine solution instilled onto the back of the protruded
      tongue during mouth breathing was observed. In Part 2, the airway of 39 patients
      requiring awake fibreoptic intubation was anesthetized by having them gargle
      twice with 5 ml lidocaine 2%, followed by instillation of 0.2 ml-kg(-1) or 20 ml
      lidocaine 1.5% (whichever was less) onto the dorsum of their tongues as described
      above. The efficacy of anesthesia was scored by the patient reaction (coughing or
      gagging) to instrumentation in the pharynx, at the glottis, and in the trachea;
      to passage of the tracheal tube into the trachea; and to the presence of the tube
      in the trachea. RESULTS: Lidocaine instilled on to the back of the tongue was
      swallowed initially but ultimately pooled in the pharynx and was aspirated. In
      all patients the trachea was intubated without requiring supplemental lidocaine,
      and all but one patient tolerated the tracheal tube in situ. CONCLUSION: A
      combination of lidocaine gargles and lidocaine instilled on to the back of the
      tongue and aspirated provides effective anesthesia of the pharynx, larynx, and
      trachea for awake fibreoptic intubation.

PMID- 10210044
TI  - Laryngo-pharyngeal complaints after use of the laryngeal mask airway.
AB  - PURPOSE: To compare the incidence of dysphagia, dysphonia and sore throat
      following anesthesia, using the laryngeal mask airway (LMA), among patients
      receiving intermittent positive-pressure ventilation (IPPV) and those breathing
      spontaneously (SV) and with two different concentrations of nitrous oxide (N2O)
      in oxygen. METHODS: In a prospective trial, 120 patients (ASA I-III, 16-70 yr, >
      60 kg) undergoing minor peripheral surgery were randomised into four groups with
      respect to type of ventilation and N2O concentration (50% or 66%) received. Cuff
      pressure measurements were monitored continuously. Twenty-four hours after
      surgery, patients were questioned for sore throat, dysphagia and dysphonia.
      RESULTS: At 30 min post-LMA insertion, increases in cuff pressure were 35.2+/
      17.1 mmHg (22.8%) vs 50.1+/-16.3 mmHg (32.7%) in patients breathing 50 and 66%
      N2O, respectively (P < 0.01). There were no differences in cuff pressure
      increment between patients in the SV and IPPV groups. Cuff pressure values at the
      end of surgery depended on the duration of surgery and on the concentrations of
      N2O. The overall incidence of postoperative discomfort at 24 hr was dysphagia
      11%, dysphonia 11% and sore throat 28.8%. Only two patients reported sore throat
      as more than mild. There was no relationship between cuff pressure and laryngo
      pharyngeal complaints. The incidence of dysphonia in the groups receiving IPPV
      was higher than that in the groups with spontaneous ventilation (17.2 vs 5%, P <
      0.05). CONCLUSION: Post-operative discomfort is related to the type of
      ventilation but not to variation in LMA cuff pressure.

PMID- 10210045
TI  - Fibreoptic assessment of laryngeal aperture in patients with difficult
      laryngoscopy.
AB  - PURPOSE: To determine the relationship between the area of the laryngeal aperture
      (LA) seen fibreoptically during laryngoscopy and the difficulty of tracheal
      intubation in patients with difficult laryngoscopy METHODS: In 587 adult patients
      after induction of general anesthesia and muscle relaxation, the best
      laryngoscopic view of the larynx using a Macintosh 3 blade was classified
      according to Cormack. When the LA could not be seen, with laryngoscope blade in
      place, the LA view provided by a fibreoptic bronchoscope (FOB)-camera passed
      nasally was photographed. Then, the laryngoscopist attempted to intubate the
      trachea using the Macintosh blade. Tracheal intubation requiring more than three
      attempts was defined as difficult. After the third attempt, the trachea was
      intubated orally aided by FOB. The LA view after jaw thrust during FOB-aided
      intubation was photographed. RESULTS: Laryngoscopy was difficult in 17 of 587
      patients. In four, intubation was difficult. In the remaining 13 patients the
      trachea was easy to intubate. The LA area obtained by the FOB in the difficult
      group (median, 0.19; intra-quartile range, 0.14 to 0.39 cm2) was smaller than
      that in the easy group (2.43; 1.84 to 2.93 cm2)(P = 0.003). In contrast, the LA
      area provided by jaw thrust during the FOB-aided intubation in the difficult
      group (2.28; 1.99 to 2.73 cm2) was similar to that during laryngoscopy in the
      easy group. CONCLUSION: Inability of the laryngoscope to provide an adequate LA
      view is one cause of difficult intubation with the Macintosh laryngoscope in
      patients with difficult laryngoscopy.

PMID- 10210046
TI  - Double lumen tube placement with the Bullard laryngoscope.
AB  - PURPOSE: Placement of double lumen tubes (DLTs) in both normal and difficult
      airways may be considerably more difficult than standard laryngoscopy and
      intubation using standard tracheal tubes. Alternative techniques to place DLTs
      have not been uniformly successful and alternative tracheal tubes do not provide
      the versatility afforded by the DLT. We intubated the tracheas of patients
      undergoing thoracic procedures requiring DLTs with the Bullard laryngoscope (BL)
      to determine its efficacy and outline its shortcomings. METHODS: Twenty nine
      consecutive patients scheduled for general anesthesia requiring DLT were
      evaluated. The laryngeal view, time to intubation and the reason for any
      difficulty with intubation were recorded. Any patient who required a second DLT
      placement had the second attempt performed via standard laryngoscopy. RESULTS:
      The time to laryngoscopy was 9+/-5 sec, and the time to intubation was 28+/-10
      sec. All patients had Cormack scores of grade of 1 through the BL. The placement
      of the bronchial lumen of the DLT was found to be in the correct location (left
      mainstem bronchus) in 9 of 28 patients. CONCLUSION: The BL appears to be
      effective in the placing DLT into the trachea of patients.

PMID- 10210047
TI  - Clinical assessment of target-controlled infusion of propofol during monitored
      anesthesia care.
AB  - PURPOSE: To determine the plasma concentrations of propofol required to achieve
      different levels of sedation during monitored anesthesia care. METHODS: Sixty ASA
      I-II, 18-65 yr-old patients, received a target-controlled continuous iv infusion
      of propofol. The target plasma concentration of propofol (Cpt) was initially set
      at 0.4 microg x ml(-1). Two minutes after calculated equilibrium between plasma
      and effect-site concentrations, the Cpt of propofol was increased by 0.2 microg x
      ml(-1) steps until the patient showed no reaction to squeezing the trapezius. The
      level of sedation was assessed immediately before each increase in propofol Cpt
      using the Observer's Assessment of Alertness/Sedation (OAA/S) scale. RESULTS: The
      Cpt of propofol required to induce lethargic response to name was 1.3 microg x
      ml(-1) (5 degrees and 95 degrees percentiles: 1.0 - 1.8 microg x ml(-1)), to
      obtain response after loud and repeated calling name was 1.7 microg x ml(-1) (1.2
      - 2.2 microg x ml(-1)), to obtain response after prodding or shaking was 2.0
      microg x ml(-1) (1.6 - 2.6 microg x ml(-1)), to obtain response after squeezing
      the trapezius was 2.4 microg x ml(-1) (1.8 - 3.0 microg x ml(-1)). Patients
      showed no response after squeezing the trapezius at 2.8 microg x ml(-1) (2.0 -
      3.6 microg x ml(-1)). Correlation between Cpt propofol and sedation scores were r
      = 0.76, P < 0.0001. CONCLUSIONS: Target-controlled infusion of propofol provided
      easy and safe management of intraoperative sedation, allowing fast and
      predictable deepening in the level of sedation, while minimizing systemic side
      effects of intravenous sedation due to the minimal risk of overdosing the drug.

PMID- 10210048
TI  - Comparison of the hemodynamic effects of sevoflurane anesthesia induction and
      maintenance vs TIVA in CABG surgery.
AB  - PURPOSE: To compare the hemodynamic effects of sevoflurane when used for
      induction and maintenance of anesthesia with a total intravenous technique in
      patients with known coronary artery disease (CAD). METHODS: Thirty patients
      undergoing elective coronary artery bypass graft (CABG) were randomly allocated
      to receive either sevoflurane (S group, n = 15) at a minimal concentration of 4%
      in oxygen for induction and at 0.5-2 MAC end-tidal concentration for maintenance,
      or a total intravenous technique (T group, n = 15) consisting of midazolam for
      induction and propofol for maintenance. In both groups, anesthesia was
      supplemented with sufentanil and muscle relaxation with cis-atracurium.
      Hemodynamic measurements included systemic and pulmonary pressures, heart rate,
      mixed venous oxygen saturation and cardiac output at the following times: pre
      induction, 7 and 25 min post-induction, chest closure, one hour after surgery and
      pre and post tracheal extubation. RESULTS: More patients in the S group (8/15)
      presented bradycardia in the induction period (T:2/15) (P = 0.05). During
      maintenance of anesthesia, treatment of hypertension was more frequent in the T
      group (12/15) than in the S group (6/15) (P = 0.025). All other parameters were
      comparable. CONCLUSION: Induction of anesthesia in patients with CAD, VCRII with
      sevoflurane supplemented by sufentanil provided hemodynamic responses comparable
      with those of TIVA although bradycardia was observed more often with sevoflurane.
      Intraoperative control of systemic blood pressure was achieved with fewer
      interventions with a sevoflurane/sufentanil maintenance than with a
      propofol/sufentanil technique in CABG surgery.

PMID- 10210049
TI  - Response to surgical stress in elderly patients and Alzheimer's disease.
AB  - PURPOSE: To determine the effect of surgical stress on plasma epinephrine,
      norepinephrine, ACTH and cortisol concentrations in patients aged 80-99 yr and in
      patients complicated with Alzheimer's disease. METHODS: A prospective controlled
      study was undertaken in 55 undergoing surgical reduction of femur neck fracture
      in Hirosaki University hospital and Hakodate Watanabe hospital; 18 patients in 80
      99 yr (Group 1) and 18 patients in 40-59 yr (Group 2) and 7 patients (Group A)
      with and 12 patients (Group B) without Alzheimer's dementia (AD) aged 60-79 yr.
      RESULTS: The increase in plasma norepinephrine level (274%) of group 1 patients,
      15 min after skin incision was higher than that in group 2 (191%) (P < 0.01).
      Mean plasma cortisol levels (40.4+/-4.7 and 44.1+/-5.2 microg x dl(-1)) of group
      1, 15 min after skin incision and 60 min after the end of surgery were
      significantly higher than the 29.8+/-3.5 and 22.3+/-3.0 microg x dl(-1) of group
      2 (P < 0.05). Plasma norepinephrine (1092.9+/-112.0 pg x ml(-1)) and cortisol
      concentrations (53.4+/-5.8 microg x dl(-1)) in group A were higher than in group
      B (772.6+/-82.4 pg x ml(-1) and 41.7+/-4.3 microg x dl(-1)) 15 min after skin
      incision (P < 0.05). CONCLUSIONS: Plasma norepinephrine and cortisol responses to
      surgical stress are activated in elderly patients and in patients with
      Alzheimer's disease.

PMID- 10210050
TI  - Control of shivering under regional anesthesia in obstetric patients with
      tramadol.
AB  - PURPOSE: Tramadol in a dose of 1 mg x kg(-1) iv is effective in the treatment of
      shivering after general anesthesia. The current study aimed to investigate (1)
      whether tramadol was equally effective for shivering under regional anesthesia in
      obstetric patients and (2) whether effective treatment could be achieved with
      lower doses. METHODS: In a randomised, double-blind study, 36 obstetric patients
      who shivered during Cesarean section under regional anesthesia and who requested
      anti-shivering treatment were allocated to one of three groups for iv treatment:
      Group T0.5 received tramadol 0.5 mg x kg(-1) (n = 12), Group T0.25 tramadol 0.25
      mg x kg(-1) (n = 13) and Group NS normal saline 0.05 ml x kg(-1) (n = 11).
      Treatment efficacy was evaluated subjectively by the parturient as no
      improvement, slight improvement, or marked improvement. The attending
      anesthesiologist who was blinded also independently noted the time elapsed from
      treatment to the time shivering subsided. Side effects such as nausea, vomiting
      or sedation and Apgar scores of the newborn were also noted. RESULTS: Eighty
      percent of parturients in Group T0.5 and 92% in Group T0.25 were judged by
      observers to have shivering controlled compared with 27% in Group NS (P < 0.001).
      The response rates of Group T0.5 and Group T0.25 were not different. There was no
      increased incidence of side effects in the treatment groups. CONCLUSION: We
      conclude that tramadol iv was effective in the treatment of intraoperative
      shivering during regional anesthesia for Cesarean section. There was no
      demonstrable difference in response rate or incidence of side effects between the
      two doses of 0.5 mg x kg(-1) and 0.25 mg x kg(-1).

PMID- 10210051
TI  - Hyperventilation after tourniquet deflation prevents an increase in cerebral
      blood flow velocity.
AB  - PURPOSE: In this study we examined whether normocapnia maintained by
      hyperventilation after lower limb tourniquet deflation prevents an increase in
      cerebral blood flow velocity. METHODS: Thirteen patients, undergoing elective
      orthopedic surgery, requiring a pneumatic tourniquet around the lower extremity,
      were divided into two groups. In group 1, ventilation was controlled at tidal
      volume of 10 mL x kg(-1) and respiratory rate of eight per minute after
      tourniquet release. In group 2, ventilation was controlled to maintain P(ET)CO2
      between 30 and 35 mmHg after tourniquet release. Arterial blood pressure, heart
      rate, peak and mean middle cerebral artery (MCA) flow velocity, and arterial
      blood gas were measured every minute for ten minutes after tourniquet release.
      The MCA blood flow velocity was measured using Transcranial Doppler
      ultrasonography (TCD). RESULTS: In group 1, the maximum peak MCA flow velocity
      was 53+/-6 cm x sec(-1) (50%+/-6% increase compared with pre- release value), and
      achieved 3+/-0.4 min after tourniquet release. In group 2, there was no increase
      either in mean or peak MCA velocity after tourniquet release. CONCLUSIONS:
      Normocapnia maintained by hyperventilation after tourniquet deflation prevents an
      increase in cerebral blood flow velocity.

PMID- 10210052
TI  - Complete atrioventricular block during anesthesia.
AB  - PURPOSE: To describe a case of asymptomatic first degree atrioventricular block
      with a bifascicular block that progressed to complete atrioventricular block
      during anesthesia. This potentially fatal block was successfully treated with
      transesophageal ventricular pacing. CLINICAL FEATURES: A 67-yr-old man was
      scheduled for microvascular decompression of the right trigeminal nerve under
      general anesthesia. His preoperative ECG showed first degree atrioventricular
      block with complete right bundle branch block and left anterior hemiblock, but he
      had experienced no cardiovascular symptoms. Anesthesia was induced with
      sevoflurane 5%, and maintained with isoflurane 1.5-2% in oxygen. Fifteen minutes
      later in the left lateral decubitus position, the systolic arterial blood
      pressure suddenly decreased from 80 mmHg to 0 mmHg. Then, the ECG abruptly
      changed from sinus rhythm to complete atrioventricular block. The heart was
      unresponsive to drug therapy such as atropine 1.3 mg and isoproterenol 0.5 mg, or
      transcutaneous pacing but transesophageal pacing was successful. CONCLUSION:
      Asymptomatic first degree atrioventricular block with bifascicular block advanced
      to complete atrioventricular block during anesthesia. The block was successfully
      managed with transesophageal pacing.

PMID- 10210053
TI  - Gastroesophageal reflux during spontaneous respiration with the laryngeal mask
      airway.
AB  - PURPOSE: To determine the incidence of gastroesophageal reflux during general
      anesthesia with the Laryngeal Mask Airway (LMA). METHODS: Twenty unpremedicated
      patients with no risk factors for reflux having day case anesthesia were
      included. Type of surgery was Orthopedic (n=8), General (n=7) and Gynecological
      (n=5). The average duration of anesthesia was 38.1 min, range 12 - 71 min.
      Anesthesia was induced with 1-2 microg x kg(-1) fentanyl and 2-3 mg x kg(-1)
      propofol and maintained with oxygen 33%, nitrous oxide 66% and isoflurane 1% (end
      tidal). Ventilation by hand was performed until spontaneous respiration resumed.
      To facilitate surgery, 13 patients were placed in the supine and seven in the
      lithotomy positions. Two pH-sensitive electrodes were used to identify reflux.
      One was placed in the oesophagus 20 cm from the anterior nares to detect
      esophageal reflux and the other was placed through the bars of the LMA to detect
      refluxing material around the LMA. RESULTS: Esophageal reflux occurred in 12
      patients (60%), in five of the 13 in the supine position and in all patients in
      the lithotomy position. The LMA electrode detected a decrease in pH in four cases
      (20%), all in the lithotomy position. The incidence reflux in the lithotomy and
      supine positions was different (Exact Probability test; P = 0.01). CONCLUSION:
      This study suggests that the lithotomy position predisposes patients to a higher
      risk of aspiration than the supine position when using a LMA.

PMID- 10210054
TI  - Epidural hematoma following epidural catheter placement in a patient with chronic
      renal failure.
AB  - PURPOSE: We report a case of epidural hematoma in a surgical patient with chronic
      renal failure who received an epidural catheter for postoperative analgesia.
      Symptoms of epidural hematoma occurred about 60 hr after epidural catheter
      placement. CLINICAL FEATURES: A 58-yr-old woman with a history of chronic renal
      failure was admitted for elective abdominal cancer surgery. Preoperative
      laboratory values revealed anemia, hematocrit 26%, and normal platelet, PT and
      PTT values. General anesthesia was administered for surgery, along with epidural
      catheter placement for postoperative analgesia. Following uneventful surgery, the
      patient completed an uneventful postoperative course for 48 hr. Then, the onset
      of severe low back pain, accompanied by motor and sensory deficits in the lower
      extremities, alerted the anesthesia team to the development of an epidural
      hematoma extending from T12 to L2 with spinal cord compression. Emergency
      decompressive laminectomy resulted in recovery of moderate neurologic function.
      CONCLUSIONS: We report the first case of epidural hematoma formation in a
      surgical patient with chronic renal failure (CRF) and epidural postoperative
      analgesia. The only risk factor for the development of epidural hematoma was a
      history of CRF High-risk patients should be monitored closely for early signs of
      cord compression such as severe back pain, motor or sensory deficits. An opioid
      or opioid/local anesthetic epidural solution, rather than local anesthetic
      infusion alone, may allow continuous monitoring of neurological function and be a
      prudent choice in high-risk patients. If spinal hematoma is suspected, immediate
      MRI or CT scan should be done and decompressive laminectomy performed without
      delay.

PMID- 10210055
TI  - A new technique of continuous interscalene nerve block.
AB  - PURPOSE: To describes a technique of indwelling interscalene catheter placement
      and to evaluate its complications. METHODS: One hundred and twenty patients
      undergoing major shoulder surgery received interscalene nerve block (ISNB) and
      were studied in three groups. Group 1 ISNB using Winnie's technique; group 2 by
      Winnie's technique with nerve stimulator and group 3 by epidural needle and
      catheter technique with nerve stimulator. All patients received 20 mL bupivacaine
      0.5% and group 3 patients received an additional bupivacaine 0.25% infusion.
      Diaphragmatic movements were measured sonographically on emergence from
      anesthesia. Complications were noted. A visual analogue scale (0-10) was used to
      assess pain four hours postoperatively. RESULTS: Mean ipsilateral diaphragmatic
      movements were 4+/-8, 14+/-11 and 18+/-8 mm (mean +/- SD) in groups 1, 2 and 3
      respectively. This was less than contralateral movements in all three groups (P <
      0.05). None of the patients in groups 2 and 3 reported postoperative pain. The
      block failed in 10% of group 1 patients. Complete ipsilateral phrenic nerve block
      occurred in 85% of the patients in group 1, 35% of group 2 and 20% of group 3 (P
      < 0.05). Ipsilateral recurrent laryngeal nerve paralysis occurred in 20% of the
      patients in group 1, 5% of group 2 and in none of the patients in group 3 (P <
      0.05). Horner's syndrome was noted in group 1 (30%), group 2 (12%) but not in
      group 3. None of the catheters in group 3 patients dislodged after an average use
      of 2.8+/-2.1 days. CONCLUSIONS: Indwelling catheter placement into the brachial
      plexus sheath as described in this communication was effective and associated
      with few complications.

PMID- 10210056
TI  - Acute lung injury after tracheal instillation of acidified soya-based or Enfalac
      formula or human breast milk in rabbits.
AB  - PURPOSE: The aim of this study was to compare the severity of the acute lung
      injury after tracheal instillation of acidified soya-based or Enfalac infant
      formula, or human breast milk (HBM) in anesthetized rabbits. METHODS: Alveolar
      arterial oxygen tension gradient (A-aDO2) and dynamic compliance were measured
      before (baseline) and hourly for four hours after tracheal instillation of 0.8 ml
      x kg(-1) soya-based or Enfalac infant formula or HBM (all acidified to pH 1.8
      with hydrochloric acid) or no fluid (control) in 24 anesthetized and
      tracheotomized adult rabbits. The A-aDO2, the difference between alveolar and
      arterial oxygen tensions, was corrected for barometric pressure and carbon
      dioxide tension. Dynamic compliance was the ratio of the expired tidal volume to
      the peak inspiratory airway pressure, normalized to body weight. RESULTS:
      Baseline A-aDO2 and dynamic compliance were similar among the four groups. In the
      control rabbits, A-aDO2 remained unchanged throughout the four hours, whereas
      mean A-aDO2 increased 180 mm Hg in the soya-based group (P < 0.0025) and 350 and
      275 mm Hg in the Enfalac and HBM groups respectively (P < 0.0002). The order of
      the A-aDO2 post-instillation was Enfalac approximately/= HBM > soya > control (P
      < 0.0002). Dynamic compliance decreased 10-12% in the control rabbits during the
      four post-instillation measurements compared with baseline (P < 0.033), decreased
      20% in the soya-based group (P < 0.0002) and 40-50% in the Enfalac and HBM groups
      (P < 0.0002). CONCLUSION: The severity of the acute lung injury after
      intratracheal instillation of infant feeds in a volume of 0.8 ml x kg(-1) and at
      pH 1.8 in rabbits depends in part, on the type of feed: Enfalac approximately/=
      HBM > soya > control.

PMID- 10210057
TI  - Inhalational and local anesthetics reduce tactile and thermal responses in mimosa
      pudica.
AB  - PURPOSE: In reaction to a variety of stimuli, the sensitive plant mimosa pudica
      closes its leaflets and drops its stems. The objective was to investigate the
      effects of anaesthetics on the reaction of mimosa pudica to a variety of stimuli.
      METHODS: The ability of the plants leaflets to close (n=4, Q5min.) was tested
      after exposure to halothane 4% and 6L x min(-1) O2, or 6L x min(-1) O2. Lidocaine
      2% or vehicle were administered through the roots, cut stems, or sprayed on the
      leaves (n=4). The test consisted of stimulating the leaves, by burning their tips
      (lidocaine experiments) or touching them with a metal rod (halothane); the
      closing of the leaflets, or the lack thereof was then observed. RESULTS: After 15
      min exposure to halothane, the mimosas had slow and incomplete reactions to
      tactile stimulation. Following 20 min exposure, the plants had no visible
      reaction to touch, a stimulus which would normally cause the collapse of the
      entire leaf. After one minute, mimosa leaves sprayed with lidocaine had no
      reaction to a lit match being touched to the tips of the leaves, contrary to the
      control in which the leaves collapsed completely. After exposure to lidocaine 2%
      through the roots and cut stems, the mimosa's reactivity gradually decreased;
      after four hours the leaves were insensitive or had slow reaction to tactile
      stimuli. CONCLUSIONS: Inhalational and local anesthetics inhibited motor
      mechanisms of the mimosa plant. This may be a model to elucidate the mechanisms
      of action of anesthetics.

PMID- 10210059
TI  - New media.

PMID- 10210058
TI  - Contamination susceptibility of three needleless and one standard needle
      injection systems.
AB  - PURPOSE: To compare in vitro the contamination susceptibility of three needleless
      and one standard needle injection systems. METHODS: The Baxter InterLink, St.
      Paul Medical Key-Lok, Braun SafSite, and Becton Dickinson heparin lock, were
      compared. Fifty of each were studied. Each system was connected to a culture
      bottle and injected 30 times over 72 hr. The manufacturers' directions were
      followed except for Braun's, which recommend that a new sterile cap be used after
      each injection. Instead, the same cap was used after each injection to reflect
      day-to-day clinical practice. Culture bottles were subsequently analyzed for
      bacterial growth. RESULTS: The contamination rates for the heparin lock,
      InterLink, Key-Lok, and SafSite were 3/50 (6%), 6/50 (12%), 4/50 (8%), and 36/50
      (72%), respectively. All positive cultures grew coagulase-negative staphylococcus
      species. There was no difference in contamination rates between the InterLink,
      Key-Lok, and heparin lock designs. The contamination rate of the SafSite was
      higher (P < 0.001) than the other three systems. CONCLUSIONS: The InterLink and
      Key-Lok systems had a similarly low contamination susceptibility as a standard
      needle injection system. It was not clear if the high contamination rate found
      with the SafSite system was due to non-adherence to the manufacturer's directions
      for handling.

PMID- 10210060
TI  - The Trachlight--a few more lessons.

PMID- 10210061
TI  - Prevention of aspiration during combitube insertion.

PMID- 10210063
TI  - Patient-controlled transnasal butorphanol analgesia following outpatient surgery.

PMID- 10210062
TI  - The difficult airway and BURP--a truly Canadian perspective.

PMID- 10210064
TI  - Improved patient comfort after transsphenoidal surgery with a modified nasal
      packing.

PMID- 10210065
TI  - Combined spinal and epidural anesthesia for major abdominal surgery in infants.

PMID- 10210066
TI  - The measurement of subacromial contact pressure in patients with impingement
      syndrome.
AB  - This study presents the subacromial contact pressure findings in 25 patients who
      underwent an arthroscopic acromioplasty for impingement syndrome. All patients
      failed a course of conservative management before surgery. Patients were
      evaluated, both before and after acromioplasty, by examination, UCLA functional
      score, and radiographic assessment of acromial morphology. At the time of
      surgery, a 4 x 10 mm air-filled catheter was placed beneath the anterior aspect
      of the acromion under arthroscopic visualization. Subacromial contact pressures
      were recorded throughout an arc of shoulder motion. Mean pressure and standard
      deviation were derived from three trials. This protocol was performed on all
      patients and the results were statistically evaluated. The mean subacromial
      pressure before acromioplasty was 11.7, 35.6, 50.1, 51.1, and 57.4 mm Hg at
      abduction arcs of 0 degrees , 90 degrees , and 180 degrees, hyperabduction
      (forced passive limit of abduction), and cross-reach (arm adducted across the
      patient's chest with the shoulder internally rotated), respectively. The pressure
      after acromioplasty decreased to 1.6, 7.8, 15.9, 22.8, and 16.5 mm Hg,
      respectively. This decrease was significant in all positions (P = .016 at 0
      degrees and <.001 in all other positions). At 90 degrees of abduction, pressure
      always decreased in internal rotation and increased in external rotation. Maximal
      contact pressure developed in either hyperabduction or cross-reach in all
      patients except two. Preoperative testing for the position of maximum impingement
      pain generally correlated with the position of maximum contact pressure.

PMID- 10210067
TI  - Arthroscopic debridement and acromioplasty versus mini-open repair in the
      treatment of significant partial-thickness rotator cuff tears.
AB  - Partial tears of the rotator cuff, especially of the articular side, have
      received attention only with the recent ability of magnetic resonance imaging
      (MRI) and arthroscopy to diagnose these lesions. Several early reports showed
      nearly 100% success in managing these lesions with arthroscopic debridement with
      or without acromioplasty. This series compares 32 patients with significant
      partial-thickness rotator cuff tears treated with debridement and acromioplasty
      versus 33 patients with mini-open repair. Follow-up was from 2 to 7 years.
      Preoperative MRI was not useful; when positive, preoperative arthrography was
      useful for articular side tears. Of the tears, 12% were bursal side tears and the
      remainder were articular side tears; all were at least 50% or more of the
      thickness of the tendon. A significant number of the arthroscopic group had fair
      results by UCLA score criteria. Three patients reruptured the remaining cuff
      later despite adequate acromioplasty. Healing of the partial tear was never
      observed at second-look arthroscopy. Although postoperative pain was
      significantly greater and recovery slower with open repair, no patient was
      reoperated on and rerupture of the repair did not occur. The outstanding results
      of prior studies of cuff debridement were not duplicated in this series of cuff
      debridements with long-term follow-up. Adequate acromioplasty alone does not
      prophylactically prevent rotator cuff tear progression. Recognition and repair of
      these significant partial tears may be advisable for the long-term function of
      the shoulder despite short-term improvement in morbidity with arthroscopic
      treatment.

PMID- 10210068
TI  - Hip arthroscopy for acetabular labral tears.
AB  - The purpose of this study is to better understand the history, physical
      examination, imaging, and outcome of arthroscopic debridement of acetabular
      labral tears. We performed a review of all 290 patients who underwent hip
      arthroscopy at our institution to identify those who have undergone arthroscopic
      debridement of an acetabular labral tear. Patients were assessed at follow-up by
      a physician visit or telephone interview and questioned as to pain, mechanical
      symptoms, activity level, work status, sports ability, and performance of
      activities of daily living. Patients were followed-up for a minimum of 1 year or
      until they underwent total hip arthroplasty (THA). All 28 patients meeting the
      study criteria were available for follow-up (mean age, 41 years; range, 14 to 70
      years) at an average of 34 months after surgery (range, 13 to 100 months).
      Average duration of symptoms before arthroscopy was 25 months. Eighteen (64%)
      patients were noted to have mechanical symptoms such as clicking or locking. Ten
      patients were noted to have a specific inciting event that initiated their
      symptoms. Magnetic resonance imaging identified the labral tear in 5 of 21 (24%)
      cases; arthrography identified the tear in 1 of 8 (13%). Of the 28 tears
      identified, there were 12 radial flap, 5 degenerative, 5 bucket handle, 3
      horizontal cleavage, and 3 peripheral longitudinal tears. Seventeen were located
      anteriorly, 7 were located posteriorly, and 4 were located superiorly. Patients
      were stratified into two groups based on the presence of significant joint
      arthritis on radiographs. Of those without arthritis, 10 of 14 (71%) had good to
      excellent results, and 2 patients underwent total hip arthroplasty at an average
      of 52 months after surgery. Of those with arthritis, 3 of 14 (21%) had good to
      excellent results, and 6 patients underwent THA at an average of 14 months after
      surgery. There were three cases of complications consisting of nerve palsies (two
      sciatic, one pudendal) that resolved completely without any remaining functional
      or sensory deficits.

PMID- 10210069
TI  - Acetabular labral tear: arthroscopic diagnosis and treatment.
AB  - We reviewed the cases of 10 patients with acetabular labral tear diagnosed and
      treated arthroscopically. The posterior portion of the labrum had a tear lesion
      in 7 patients, the anterior portion in 4, and the superior portion in 1. A
      longitudinal tear was found in 8 patients, a degenerative tear in 1, and
      fibrillation in 1. Eight patients who were treated by arthroscopic partial
      limbectomy experienced prompt pain relief, and were free of symptoms at the
      latest follow-up. The remaining 2 patients were treated conservatively but their
      symptoms did not subside. The following three findings were highly indicative of
      a torn acetabular labrum in the current study: (1) Pain elicited by internal
      rotation with the joint flexed 90 degrees, (2)pain elicited by axial compression
      to the joint flexed 90 degrees and slightly adducted, and (3) tenderness
      posterior to the greater trochanter. These findings were positive in 7, 10, and 8
      patients, respectively. To diagnose acetabular labral tear, these signs and
      arthroscopy are useful. Hip joint-Labral tear.

PMID- 10210070
TI  - Arthroscopic debridement for osteoarthritis of the knee: predictors of patient
      satisfaction.
AB  - A retrospective review of 204 knees with osteoarthritis debrided arthroscopically
      was carried out to determine possible predictors of patient satisfaction with the
      outcome of their procedure. Knees were divided into three groups based upon the
      alignment on a standing anteroposterior radiograph in extension: group I, 0
      degrees; group II, <5 degrees ; and group III, >5 degrees. Each group was further
      subdivided as to whether the patients were better (satisfied), unchanged, or
      worse (unsatisfied) with their operation at the time of review. There were 81 men
      (42.6%) and 109 women (57.4%) ranging in age from 30 to 88 years (mean, 62.1
      years). Follow-up ranged from 2 to 15 years (mean, 7.4 years). Overall, 63.2%
      (129 knees) were better, 21.1% (43 knees) were unchanged, and 15.7% (32 knees)
      were worse after surgery. Further surgery was needed in 54 knees (26.5%).
      Regarding satisfactory results, group I (n = 57) had 84.2%, group II (n = 102)
      had 67.6%, and group III (n = 45) had 26.7%. Based on statistical analysis, it is
      concluded that patients with less deviated axes do better than those with large
      angulations, prior surgery predisposes to poorer results, and while the age was
      lower in the better and unchanged groups, it seems to be secondary in importance
      to angular deformity. Arthroscopic debridement is a successful palliative,
      temporizing treatment for the osteoarthritic knee.

PMID- 10210071
TI  - The radiographic position of medial and lateral meniscal horns as a basis for
      meniscal reconstruction.
AB  - This investigation attempted to determine the radiographic position of human
      meniscal horn bony insertion sites. This information would prove vital for
      anatomically correct osseous tunnel placement necessary for the restoration of a
      functional meniscus after reconstructive surgery. The native bony insertion sites
      of the medial and lateral meniscus in 13 fresh-frozen human cadaver knees were
      radiographically examined. After insertion site outline with 22-gauge fine wire,
      anteroposterior and lateral radiographs were obtained. Radiographic landmarks
      were then described in detail. Each meniscal horn was found to have a distinct
      bony insertion site with characteristic and consistent radiographic landmarks
      defining its margins. Using an arthroscopic guide, 3/32-inch fine wires were
      drilled into the center of the lateral (5 specimens) and medial (5 specimens)
      meniscal horns to validate these locations and to establish the clinical
      usefulness of these measures. Improved understanding of meniscal horn insertion
      site locations should improve osseous tunnel placements during meniscal
      transplantation. In the presence of a properly sized allograft, anatomically
      correct tunnel placement increases the likelihood of restoring normal meniscal
      function.

PMID- 10210072
TI  - Acute and long-term response of the meniscus to partial meniscectomy using the
      holmium: YAG laser.
AB  - The purpose of this study was to evaluate the histological effects of holmium:YAG
      laser partial meniscectomy in an in vivo rabbit model and compare it with scalpel
      partial meniscectomy at selected time intervals. Twenty-four adult male New
      Zealand rabbits underwent bilateral partial medial meniscectomies through the
      avascular zone. In the right knee, partial medial meniscectomy was performed
      using a standard surgical blade; in the left knee, an anatomically similar
      partial medial meniscectomy was performed using a Ho:YAG laser (Coherent, Santa
      Clara, CA). All animals were randomized and three animals were killed at
      postoperative days I and 3, and postoperative weeks 1, 2, 3, 4, 6, and 10.
      Samples of all medial and lateral menisci, with attached synovium and vascular
      rim, from both knees were harvested and submitted for histological and/or
      ultrastructural examination. The results indicate that (1) at all time periods,
      laser cut menisci had more cell loss and matrix degradation; (2) synovial
      necrosis was more common in laser-treated knees; (3) the Ho:YAG laser creates
      three zones of damage in the meniscal fibrocartilage: a zone of fibrin and debris
      at the incision site, a zone of necrosis characterized by degeneration of the
      collagen and loss of viable cells, and a zone of thermal change characterized by
      collagen degeneration. The zone of thermal change, with its histological injury
      was thought at the time of surgery to be the viable border. The zone of thermal
      change may act as a barrier to delay healing, and the scalpel produced a
      consistently straighter cut.

PMID- 10210073
TI  - Anterior cruciate ligament reconstruction alters the patellar alignment.
AB  - Although there are many articles dealing with anterior cruciate ligament (ACL)
      reconstruction, there are none dealing with the possibility of changes of the
      patellofemoral alignment after these procedures. Forty-six patients were
      evaluated preoperatively and 1 year postoperatively, after undergoing intra
      articular ACL reconstruction, for changes of the patellofemoral alignment.
      Patella-tilt and congruence angles were measured on tangential view radiographs
      that were taken in the supine position. Analysis of covariance was performed and
      revealed a significant change of the congruence angle 1 year postoperatively. The
      patella-tilt did not change. One year postoperatively, the patella shifted on
      average 5 degrees medially after ACL grafting. It can be deduced that anterior
      knee pain after ACL reconstruction could be caused by distinct changes in the
      patellofemoral alignment.

PMID- 10210074
TI  - Isokinetic evaluation of anterior cruciate ligament reconstruction: hamstring
      versus patellar tendon.
AB  - The purpose of the study was to compare the hamstring and quadriceps isokinetic
      results 6 months postoperatively in patients having patellar tendon or hamstring
      anterior cruciate ligament (ACL) reconstruction. The study group was comprised of
      106 randomly selected patients who had ACL reconstruction with either autogenous
      patellar tendon (PT), semitendinosus (ST), or semitendinosus and gracilis (ST/G).
      Hamstring and quadriceps isokinetic strength were assessed at 180 degrees/sec and
      300 degrees/sec with the results of the operatively treated leg expressed as a
      percent compared with the nonoperative leg. The mean results for knee extension
      at 180 degrees/sec were 68.3%, 74.3%, and 78.1%; and at 300 degrees/sec were
      70.7%, 76.7%, and 81.7% for PT, ST, and ST/G, respectively. The mean results for
      knee flexion at 180 degrees/sec were 86.1%, 80.6%, and 81.7%; and at 300
      degrees/sec were 77.6%, 79.1%, and 75.6% for PT, ST, and ST/G, respectively. No
      statistically significant differences were found in regard to knee extension or
      flexion strength when evaluating the different tissue sources. The results show
      that selection of autogenous hamstring or PT used for ACL reconstruction should
      not be based solely on the assumption of the tissue source altering the recovery
      of quadriceps and/or hamstring strength. In addition, a majority of the patients
      had not achieved adequate strength to safely partake in unlimited activities at 6
      months postoperatively.

PMID- 10210075
TI  - Comparison of femoral and tibial pullout forces in bone-patellar tendon-bone
      anterior cruciate ligament reconstructions with a new interference fixation
      device.
AB  - Interference screws have become the standard method for fixing bone-patellar
      tendon-bone (BPTB) grafts. To avoid the inherent pitfalls and complications of
      interference screws, a 28-mm long and from 5 to 7 mm spreadable metal bolt with
      nontapping threads was developed for this study. The technical applicability and
      biomechanical characteristics of this new BPTB interference fixation device were
      investigated by dissection or tensile testing of 48 cadaveric knee specimens from
      young donors. No problems occurred with respect to bone plug anchoring during
      insertion of the spreading bolts. The clinically important linear load was 920+/
      283 N for the femoral and 635+/-247 N for the tibial fixation site. Bone plug
      pullout was the mode of failure in all specimens. The results of this study
      indicate that the spreading bolt is a reasonable alternative to interference
      screws.

PMID- 10210076
TI  - Resulting tensile forces in the human bone-patellar tendon-bone graft: direct
      force measurement in vitro.
AB  - The objective of this study was to measure the resultant force in the human bone
      patellar tendon-bone graft after reconstruction of the anterior cruciate ligament
      under various conditions in vitro. Seven fresh-frozen cadaver lower extremities
      were used. Force measurement was made with a quartz force transducer mounted in a
      specially designed load cell. The effect of passive extension movement,
      quadriceps pull, varus torque, and valgus torque on the resultant force in the
      ligament were investigated. Passive extension of the joint generated a rapid
      increase of force in the graft between 30 degrees and 0 degrees of flexion,
      reaching its maximum (128+/-25 N) at full extension. When quadriceps pull was
      applied to extend the joint, resultant force increased at 50 degrees of flexion
      and reached its maximum (219+/-25 N) at full extension. Additional resistance
      applied to the level of the ankle joint generated an additional load of the
      graft. Increase of forces in the ligament resulted from both varus and valgus
      applied moments.

PMID- 10210077
TI  - The strain behavior of the anterior cruciate ligament during stair climbing: an
      in vivo study.
AB  - Stair climbing is a closed kinetic chain exercise that is thought to be useful
      for knee rehabilitation following anterior cruciate ligament (ACL) reconstruction
      while protecting the graft from excessive strain. The objectives of this study
      were to measure the strain produced in the anteromedial band (AMB) of the normal
      ACL during stair climbing in vivo. We have previously shown that the normal AMB
      strain pattern during knee passive flexion-extension motion is similar to that of
      an ACL graft immediately after graft fixation. We successfully tested five
      subjects with normal ACLs, who were candidates for arthroscopic meniscectomy
      under local anesthesia. AMB strain was measured in vivo using the Differential
      Variable Reluctance Transducer (MicroStrain, Burlington, VT). The stair climbing
      activities were performed on a StairMaster 4000PT (Randall Sports Medicine,
      Kirkland, WA). Two different climbing cadences were evaluated; 80 and 112 steps
      per minute. Consistent with our previous studies of ACL biomechanics, strain
      values increased as the knee was moved from a flexed to an extended position. The
      mean peak AMB strain values for the 80 and 112 steps per minute conditions were
      2.69% (+/-2.89&) and 2.76% (+/-2.68%), respectively. These values were not
      significantly different. Compared with other rehabilitation activities previously
      tested in the same manner, the AMB strain values produced during stair climbing
      were highly variable across subjects. High strain values were observed in some
      patients but not in others.

PMID- 10210078
TI  - Return of motion after simultaneous repair of displaced bucket-handle meniscal
      tears and anterior cruciate ligament reconstruction.
AB  - Patients with displaced bucket-handle (DBH) meniscal tears in anterior cruciate
      ligament (ACL)-deficient knees are prone to flexion contracture following
      meniscal repair and simultaneous ACL reconstruction. It has been suggested that
      ACL reconstruction be delayed until full range of motion has returned after the
      meniscal repair. A retrospective analysis was performed comparing the return of
      extension in patients undergoing simultaneous ACL reconstruction and repair of
      DBH tears (group A) versus a control group of patients with non-DBH tears (group
      B). Age, sex, body mass index, duration of time from injury to surgery, and
      preoperative extension were also compared between groups and evaluated for their
      significance as risk factors. Patients in group A achieved recovery to -5 degrees
      and 0 degrees of extension 22% and 35% more slowly, respectively, when compared
      with group B. These differences were not statistically significant. Female
      patients tended to heal more rapidly in both groups. We conclude that a one-stage
      procedure is sufficient in allowing patients with DBH tears in ACL-deficient
      knees to regain a functional knee to within 5 degrees of full extension.

PMID- 10210079
TI  - Arthroscopic treatment of transchondral talar dome fractures: a long-term follow
      up study.
AB  - Arthroscopic treatment of transchondral talar dome fractures allows accurate
      visualization and debridement of the lesion with less postoperative morbidity and
      earlier mobilization than arthrotomy. Although many studies document the results
      of open treatment, no reports of long-term results of arthroscopic treatment of
      these fractures have been published. We reviewed the results in 12 patients who
      had arthroscopic excision and curettage of a transchondral talar dome fracture
      and had an average of 10.1 years of follow up (range, 8.1 to 13.9 years). There
      were 5 medial and 7 lateral lesions. According to the four-stage classification
      of Berndt and Harty, 2 were stage II; 8 were stage III; and 2 were stage IV. All
      patients were evaluated with a subjective questionnaire, ankle radiographs, and a
      physical examination. The long-term subjective and objective results were good or
      excellent in 10, fair in 1, and poor in 1 patient. All patients' radiographs
      showed residual subchondral changes at the site of the original lesion, but
      minimal to no degenerative changes. Patients who are treated with arthroscopic
      debridement and curettage for transchondral talar dome fractures achieve a
      predictably high percentage of successful results with low morbidity.

PMID- 10210080
TI  - Tram track lesion of the talar dome.
AB  - A distinctive lesion in the articular cartilage of the talar dome in anterior
      bony impingement syndrome of the ankle joint is reported. During arthroscopic
      treatment of anterior bony impingement syndrome of the ankle, we found six
      distinctive articular cartilage lesions in the talar dome. The cartilage lesions
      were full-thickness defects (grade IV), located in the anterior half of the
      medial aspect of the talar dome and were longitudinal with variable widths
      resembling a tram track; thus, "tram track lesion." All six patients were
      professional or collegiate soccer players and had large osteophytes in the
      anteromedial ridge of the tibial articular margin. Instability test results were
      negative. All patients had the typical tenderness in the anteromedial comer of
      the ankle. Overall, good and excellent results were achieved in five patients at
      a mean follow-up of 27 months after arthroscopic excision of osteophytes and
      drilling using K-wires.

PMID- 10210081
TI  - Cystic hematoma formation following use of a biodegradable arrow for meniscal
      repair.
AB  - This is a case report of a cystic hematoma formation following the use of a
      biodegradable arrow for repair of a medial meniscus tear. A literature search
      found no previous report of this complication. Open hematoma debridement and
      arrow removal were effective in the treatment of this complication following all
      inside meniscal repair with a biodegradable arrow.

PMID- 10210082
TI  - Arthroscopic-assisted reduction and percutaneous external fixation of a displaced
      intra-articular glenoid fracture.
AB  - Arthroscopic reduction and percutaneous external fixation is a well-known
      technique for treating selected fractures. This is the first report of a method
      of treating intra-articular glenoid rim fracture using shoulder arthroscopy and
      percutaneous external fixation. The surgical trauma associated with open
      operative treatment of these fractures can be minimized using minimally invasive
      techniques under arthroscopic control. This technique not only allows for
      anatomic reduction with minimal surgical trauma but provides a valid diagnostic
      and treatment alternative for associated injuries. Arthroscopic reduction and
      percutaneous external fixation yielded excellent results with no complications.
      The authors describe the principles of the procedure and discuss its advantages
      compared with traditional surgery.

PMID- 10210083
TI  - Arthroscopic-assisted first metatarsophalangeal joint arthrodesis.
AB  - This is the first report of a successful first metatarsophalangeal joint
      arthrodesis using great toe arthroscopy and percutaneous internal fixation. The
      surgical trauma associated with open operative arthrodesis can be minimized using
      minimally invasive techniques under arthroscopic control. The authors describe
      the principles of the surgery and discuss the advantages compared with
      traditional surgery.

PMID- 10210084
TI  - A cadaveric study of endoscopic decompression of the cubital tunnel.
AB  - A cadaveric study of endoscopic decompression of the cubital tunnel was
      performed. Four fresh-frozen upper limbs were used for dissection, with a focus
      on the relationship between the ulnar nerve and Osborne's band. The endoscopic
      procedure was performed with the Ectra II system (Smith & Nephew, Andover, MA).
      After the surgical procedure, further dissection was done to evaluate the
      effectiveness and safety of the endoscopic cut of Osborne's band. Our conclusion
      is that endoscopic release is not a technically difficult procedure, and may be
      limited to certain clinical situations.

PMID- 10210085
TI  - "Cigar Wrap" technique for gracilis augmentation in hamstring anterior cruciate
      ligament reconstruction.
AB  - The use of Hamstring grafts for anterior cruciate ligament reconstruction is
      becoming increasingly popular. Most surgeons use a four-stranded graft consisting
      of double-stranded semitendinosus and gracilis tendons. The gracilis tendon, in
      addition to being smaller in diameter, is often shorter and more diminutive at
      its muscular end. We developed a technique for supplementing this tendon using
      excess semitendinosus tendon. This allows enhanced tibial tunnel fit and improved
      graft fixation.

PMID- 10210086
TI  - Arthroscopic resection of the radial head.
AB  - The authors describe arthroscopic radial head resection in patients with post
      traumatic arthritis after fractures of the radial head or in patients with
      rheumatoid arthritis of the elbow joint, as an expanded indication for elbow
      arthroscopy. Arthroscopic radial head resection allows the surgeon to deal with
      the intrinsic joint pathology, as well as with accompanying symptoms such as
      synovitis, capsular contracture, or loose bodies. The portals used are the
      proximal medial, anterolateral, and the midlateral portal. The anterior three
      quarters of the radial head and 2 to 3 mm of the radial neck are resected with
      the stone-cutting abrader in the anterolateral portal and the arthroscope in the
      proximal medial portal. For resection of the posterior portion of the radial
      head, the abrader may be transferred to the midlateral portal. This permits
      resection of the remnants of the radial head posteriorly and also at the proximal
      radioulnar joint. Arthroscopic treatment allows the patient to begin and maintain
      an aggressive postoperative physical therapy program immediately after surgery,
      thus decreasing the risk of anterior scarring and reoccurring contracture of the
      capsule of the elbow joint.

PMID- 10210087
TI  - A fatal pulmonary embolus after arthroscopy in a morbidly obese woman.

PMID- 10210088
TI  - Use of the SF-36.

PMID- 10210089
TI  - Rural and urban problem drinkers in six Southern states.
AB  - In 1994-1997 we conducted a four-wave longitudinal study of rural and urban
      problem drinkers in six Southern United States states to examine rural/urban
      differences in predictors of service use and course of drinking. This report
      describes early rural/urban differences from a brief interview with over 3,000
      community individuals and among 525 identified problem drinkers. Overall, we
      found rural/urban differences in alcohol consumption at the community level but
      only demographic differences among problem drinkers. Our newly developed
      screening interview for alcohol disorders had excellent agreement (kappa = 0.72)
      for lifetime disorders and good agreement (kappa = 0.53) for recent disorders
      against structured diagnostic interviews for DSM-IV criteria.

PMID- 10210090
TI  - A contextual model of adolescent alcohol use across the rural-urban continuum.
AB  - In the research presented here, we develop and test with respondents from a broad
      range of contexts a multilevel social control model of adolescent substance use,
      integrating macro- and microsociological and criminological perspectives.
      Specifically, this research examines the individual-level social control
      processes or mechanisms thought to lead to alcohol use embedded in school
      contexts in different community settings along the rural-urban continuum. In this
      way we determine 1) the main effects of individual- and contextual school-level
      variables and 2) the conditioning or moderating influences of school climate on
      individual alcohol use and on individual-level processes leading to alcohol use.
      Furthermore, given that our sample contains students from a broad range of
      settings along the rural-urban continuum, our findings address the
      appropriateness of conceptualizing rural and urban drug use and their respective
      etiologies as dichotomous. In this respect our findings suggest that
      heterogeneity in drug use exists within rural school settings as well as within
      urban school settings, and that examining rural drug use as separate from urban
      drug use is not justified.

PMID- 10210091
TI  - Readiness for drug use prevention in rural minority communities.
AB  - An assessment of community readiness for drug use prevention in rural communities
      indicated that most rural communities are at relatively low stages of readiness.
      Minority communities were particularly low in readiness, with only 2% having
      functioning drug prevention programs. Rural communities at different levels of
      readiness require different types of programs to increase readiness, i.e.,
      communities at the no awareness stage require analysis of the historical and
      cultural issues that support tolerance of drug use, those at the denial and vague
      awareness stages need specific information about local problems, and communities
      at the preplanning and preparation stages need information about effective
      programs, help in identifying resources, and assistance with staff training. In
      addition, building and maintaining effective programs requires continued
      evolution of readiness through the stages of initiation, stabilization,
      confirmation and expansion, and professionalization. Revised and updated scales
      and methods for assessing community readiness are provided.

PMID- 10210092
TI  - Rural attitudes, opinions, and drug use.
AB  - There are two primary purposes of this paper. The first is to summarize the
      results of a survey conducted in a rural area of Kentucky on attitudes and
      behaviors regarding substance use. The second purpose is to examine differences
      in drug attitudes and behaviors for higher and lower density rural areas.
      Participants for this study were contacted by telephone in March 1996. The sample
      was generated by random digit dialing for eight county telephone exchanges. The
      sample included 334 respondents from the eight counties who were grouped into
      respondents from higher density areas (n = 132) and lower density areas (n =
      202). Results indicated that respondents from both higher density and lower
      density areas were similar on drug use and attitudes. However, lower density
      areas reported their county as a worse place to live and less safe than
      respondents from higher density areas. Respondents from lower density areas were
      also more likely to report there was more alcohol/drug use and more alcohol
      bootlegging in the past year, and that bootlegging alcohol is a serious problem
      in their county. Future research could include the examination of heterogeneity
      of rural areas using different indices.

PMID- 10210093
TI  - Differences in drug use among rural and suburban high school students in Ohio.
AB  - This exploratory study examines differences in the prevalence of drug use by
      gender among twelfth grade students (n = 464) in selected rural and suburban high
      schools in west-central Ohio. The lifetime use of alcohol and other drugs is
      common among all groups. Proportionally fewer boys in rural schools than boys in
      suburban schools reported the use of marijuana, inhalants, and LSD, or recent
      episodes of drunkenness. No statistically significant differences emerged between
      girls in rural and suburban schools. Afterschool employment practices may help
      explain the observed differences.

PMID- 10210094
TI  - Drug use in very rural Alaska villages.
AB  - The Alaska Native Preschool Project was centered in the Head Start Programs of
      two typical Alaska native villages near the Bering Sea. Data were collected over
      5 years, 1990 to 1995, from preschool parents (N = 342) with surveys, a panel of
      villagers (N = 25 to 30) using qualitative interviews; villagers using
      participant observation; and a limited review of public records. The villages
      typify the changing life of Alaskan villagers who live in the Bering Straits
      area. Qualitative data indicated that a number of problems were associated with
      drug and alcohol use in the villages. The level of smokeless tobacco use from
      surveys in the previous month among preschool parents (41%) was self-reported to
      be almost 10 times greater than the national level reported in the 1995 National
      Household Survey. The use of marijuana reported by preschool parents in the
      previous month was almost 3 times higher than the 1995 National Household Survey
      estimates (19 vs 6.7%). Tobacco use in the previous month was reported at over
      56%, a level that was over 1 1/2 times the level of use at 34.7% estimated from
      the 1995 National Household Survey. For 26-34 year olds, previous month alcohol
      use was lower for the village parents than estimated from the 1995 National
      Household Survey (38 vs 63%). The self-reported levels of other drug use among
      preschool parents were very low compared with overall United States rates.

PMID- 10210095
TI  - HIV seroprevalence across the rural/urban continuum.
AB  - While the first decade of the AIDS epidemic was characterized by high prevalence
      rates of AIDS infection in urban areas, there is increasing recognition of the
      spread of HIV into rural communities in the United States. Data from the Miami
      CARES cohort collected on 3,555 chronic drug users from 1988 to 1994 provide a
      unique opportunity to assess sociodemographic characteristics, drug-using
      behaviors and HIV risk behaviors related to HIV seropositivity in three
      communities across the rural-urban continuum: Miami, Florida; Belle Glade,
      Florida and Immokalee, Florida. The three very different communities studied
      demonstrate that HIV is no respecter of ecological site. The spread of HIV
      between areas and within areas is specifically correlated with the risk factors
      including injection drug use, use of crack cocaine, exchange of sex for money,
      and the rates for sexually transmitted diseases. All of these factors are shown
      to increase the risk of HIV so that the constellation of these practices helps
      determine the differential rates and spread of HIV in the three different areas.

PMID- 10210096
TI  - Opportunities for AIDS prevention in a rural state in criminal justice and drug
      treatment settings.
AB  - This study examined the likelihood that drug users would receive HIV/ AIDS
      prevention information and supplies (e.g., condoms and bleach) in the rural state
      of Kentucky. Despite evidence of high HIV risk among criminal justice and
      substance-using populations, incarceration and substance-user treatment were only
      minimally associated with prior HIV prevention exposure or HIV testing. These
      data strongly support the use of criminal justice and treatment settings to
      provide AIDS prevention interventions for the high-risk drug-using populations
      they serve, and to target HIV prevention services in rural as well as urban
      areas.

PMID- 10210097
TI  - AIDS susceptibility in a migrant population: perception and behavior.
AB  - Within the framework of the Health Belief Model, this paper examines correlates
      of perception of AIDS susceptibility among 846 drug-using migrant farm workers
      and their sex partners. Significant but relatively small differences by ethnicity
      and gender were found. The data showed a consistent significant statistical
      relationship between frequency of drug use, high-risk sexual behavior, and
      perception of AIDS susceptibility. Perception of AIDS susceptibility was
      significantly related to a subsequent reduction in sexual risk behaviors.
      Consistent with the Health Belief Model, the data suggest that increasing
      perception of AIDS susceptibility may be an important motivator in reducing high
      risk behaviors.

PMID- 10210099
TI  - Behavior changes among crack-using rural and urban women.
AB  - This study compared rural and urban crack-using women and examined their
      responses to two interventions. A prospective cohort study design was employed to
      assess the effectiveness of standard and innovative HIV prevention interventions
      on 541 urban and 268 rural women in Florida. Generalized estimating equation
      analysis, accounting for repeated measures, found that for combined urban and
      rural samples, the innovative intervention was more effective than the standard
      for a number of drug and sexual risk behaviors. However, the analysis indicated
      no significant differences in intervention efficacy between rural and urban
      women. The results imply that there is a need for similar HIV prevention services
      in both areas.

PMID- 10210098
TI  - Drug use and HIV risks among migrant workers on the DelMarVa Peninsula.
AB  - Because high rates of drug use have been documented in the migrant farm worker
      population, the National Institute on Drug Abuse funded the Migrant Health Study
      to examine HIV risk behaviors among drug-using farm workers and their sexual
      partners. Many of these individuals were home-based in South Florida and migrated
      during the work season to various points along the Eastern Migratory Stream. The
      focus of this paper is a description of the characteristics and behaviors of the
      151 respondents contacted on the DelMarVa Peninsula during 1994 and 1995. The
      data indicate that drug use was widespread in this population, a significant
      proportion were at risk for HIV infection, and 6% were HIV positive. As a result
      of these findings, public health agencies on the peninsula have instituted HIV
      education programs in those clinics utilized by both local and transient
      agricultural workers.

PMID- 10210100
TI  - Crack cocaine use in rural migrant populations: living arrangements and social
      support.
AB  - Correlates of crack cocaine use were studied among a targeted sample of migrant
      workers and their sexual partners (n = 571) in rural Southern Florida. Employment
      among men and recent drug-user treatment among men and women are positively
      related to crack use, as is involvement in crime and prostitution. Among women
      but not men, living with children is negatively related to crack use. Drug use
      and HIV prevention programs should intervene with individuals and their families
      and social groups. Migrant workers and their sexual partners also need effective
      drug-user treatment with long-term relapse prevention services.

PMID- 10210101
TI  - Access to health and human services for drug users: an urban/rural community
      systems perspective.
AB  - Publicly funded drug-user treatment programs in both urban and rural areas are
      under unprecedented pressure to adapt to multiple perspectives of their mission,
      reduced governmental funding, diminished entitlement program resources for
      clients, managed care reforms, and continuing unmet need for services. This
      article describe an ongoing health services research study that is investigating
      how these and related health and human service programs currently serve and cross
      refer chronic drug users and how they perceive and are reacting to systemic
      pressures. Interim analysis on intra-agency diversity and managed care
      perceptions are reported.

PMID- 10210102
TI  - Health care need and utilization: a preliminary comparison of injection drug
      users, other illicit drug users, and nonusers.
AB  - This paper investigates the relationship between chronic drug use and the health
      care system. Data from 536 African-American, Hispanic, and non-Hispanic White men
      and women were analyzed to determine independent risk factors for three outcome
      variables: 1) Need for health care treatment, 2) Utilization of health care
      treatment, and 3) Failure to receive needed treatment. Nine independent
      demographic, health, and drug-use history variables were assessed in logistic
      regression models. Chronic drug users were more likely in the past year to need
      health care treatment, were as likely to receive some health care treatment, and
      were more likely not to receive needed treatment than were nonusers.

PMID- 10210103
TI  - Developing a rural therapy with big city approaches.
AB  - Both rural communities and urban communities experience problems associated with
      drug use and drug dependence. However, existing treatment interventions are not
      tailored for rural settings. This article describes a project which will modify
      an existing social skills behavioral therapy for rural populations, refine the
      therapy, develop a manual, train and supervise therapists, and pilot test the
      structured behavioral outpatient rural therapy to treat rural drug users and drug
      dependents as Stage I Research for NIDA's Behavioral Therapies Development
      Program.

PMID- 10210105
TI  - Recommendations to bridge rural/urban drug-use(r) research and practice.
AB  - This article presents recommendations developed by a group of United States drug
      use(r) researchers interested in rural and urban research and practice who met in
      Lexington, Kentucky, in October 1996. Overall, there was consensus about the
      importance of better understanding the urban/rural drug and alcohol
      use/dependency continuum. It was emphasized that drug and alcohol use/dependency
      are chronic and relapsing disorders. Definitions of rural and urban are most
      important, and different definitions may be associated with factors that are
      masked by population density. Specific recommendations are presented in the
      following areas: Rural Factors, Epidemiology, HIV/AIDS, Treatment and Other
      Services, Migration, Youth, Protective Factors, Systems Perspective, Measurement,
      Confidentiality, Criminal Justice, Research, Policy Research, Economic Factors,
      Service Providers, and Managed Care.

PMID- 10210104
TI  - Drug treatment experiences: rural and urban comparisons.
AB  - This study sought to investigate treatment-seeking behaviors among drug users in
      rural populations and how they compare to their urban counterparts. Data for this
      analysis were drawn from the Miami and Immokalee sites of the National Institute
      on Drug Abuse's Cooperative Agreement Program for AIDS outreach/intervention
      research study targeting high-risk out-of-treatment injection drug users and
      crack smokers. Findings indicate that Miami subjects were 2.57 times more likely
      to have been in drug treatment compared to their rural counterparts. This
      differential may be explained in terms of the availability, accessibility, and
      acceptability of health care services.

PMID- 10210106
TI  - The combination of heteroduplex analysis and protein truncation test for exact
      detection of the APC gene mutations.
AB  - Familial adenomatous polyposis (FAP) is usually associated with mutation in the
      adenomatous polyposis coli (APC) gene. To examine the occurrence of these
      mutations in the number of FAP suspected families from the whole Slovakia
      effectively, we have applied heteroduplex analysis (HDA) and protein truncation
      test (PTT) for the analyses of 2-5 base pair deletions and point mutations of the
      APC gene. In the analyzed exon 15 of the APC gene determined by the primers
      15Efor-15Grev for HDA and 15ET7-15J3 for PTT more than 70% of mutations should be
      deletions [3, 12], which are detectable by HDA. In our collection of 5 FAP
      families mutations in the APC gene were found in families 10, 27 and 41 using
      HDA. By PTT test the formation of truncated APC protein in FAP families 2, 10, 16
      and 27 were revealed. The necessity of combination of at least HDA and PTT
      techniques for exact detection of APC mutations in analyzed APC region is
      discussed.

PMID- 10210107
TI  - The single cell gel electrophoresis: a potential tool for DNA analysis of the
      patients with hematological malignancies.
AB  - Single cell gel electrophoresis (SCGE) was used to evaluate the level of DNA
      damage in peripheral blood (PB), bone marrow (BM), and lymphatic node (LN) cells
      of patients with acute lymphoblastic leukemia (ALL), acute myeloid leukemia
      (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML) and non
      Hodgkin's lymphoma (NHL). The level of DNA damage was compared with the level of
      basal DNA damage in control group, represented by healthy donors. Statistically
      significant increase of basal DNA damage was found in leukemia/lymphoma cells of
      patients suffered from AML, CML, ALL of T-cell subtype (T-ALL), and NHL, however,
      no difference in basal DNA damage was found in patients with ALL of early B-cell
      subtype (B-ALL) and CLL in comparison to control group. The mean basal DNA damage
      increased in the order CLL<early B-ALL<T-ALL<AML<CML<NHL (5.6, 7.2, 10.7, 11.9,
      16.9, and 23.4% of tail DNA, respectively) what correlated with survival
      prediction of patients with particular hematological disease. A large
      heterogeneity was found in the level of basal DNA damage among patients with AML.
      By sorting this group according to the immunophenotypic markers and cell maturity
      a good correlation was found between the level of basal DNA damage and French
      American-British (FAB) classification for AML (M1-M2 vs. M4-M5). Though T-ALL
      group manifested larger homogeneity in comparison with AML, the value of basal
      DNA damage was also dependent on T-cells maturity and coexpression of surface
      marker CD10. Chemotherapy resulted in a significant but variable increase of DNA
      damage in leukemia/lymphoma cells. No increase of DNA damage was repeatedly
      observed in leukemia/lymphoma cells of patient who did not respond to therapy.
      The level of DNA damage in cells of patients in remission decreased more or less
      to the basal level in control cells.

PMID- 10210108
TI  - Angiogenesis in endometrial cancer.
AB  - We evaluated the level of angiogenesis in endometrial adenocarcinoma and
      investigated the relationship between tumor vascularity and clinicopathological
      parameters. The level of angiogenesis in noninvaded uterine smooth muscle was
      also studied. Angiogenesis was studied in uteri of 29 post-menopausal women
      operated on for endometrial cancer. DAKO EPOS Anti-Human von Willebrand
      Factor/HRP antibodies were applied to mark endothelial cells. Both vessels and
      endothelial cells were counted on a light microscope equipped with computerized
      morphometric appliance. The highest density of vessels and endothelial cells was
      found in disease-free uterine smooth muscle tissue situated distant to the tumor.
      Density of vessels and endothelial cell counts were higher in the outer as
      compared to the central parts of the tumor. We found statistically significant
      differences in total angiogenic points' density between groups of various
      clinical FIGO staging, specifically between Ia and Ib, Ic, II. A positive
      correlation was found between the clinical stage of the disease (according to
      FIGO) and the total angiogenic points' density, density of endothelial cells and
      the density of vessels with viable lumen (counts/sq. mm calculated from the
      central parts of the tumor). These results suggest that the analysis of
      angiogenesis may be a useful biologic parameter and additional study of
      neovascularization in endometrial cancer is warranted.

PMID- 10210109
TI  - Cathepsin B, p53 expression and AgNORs in transitional cell carcinoma.
AB  - The aim of this study was to assess the relation between silver-strained
      nucleolar organizer regions (AgNOR), tumor stage, tumor grade and p53 expression
      with cathepsin B staining in transitional cell carcinoma of bladder. Tissue
      sections from 64 transitional cell carcinomas of the bladder were evaluated for
      the relation between AgNOR, tumor stage, tumor grade and p53 expression with
      cathepsin B staining in the neoplastic and stromal cells. Mean AgNOR values were
      significantly higher and the presence of p53 expression were different in
      cathepsin B positive and negative tumor and stromal cells. Although the number of
      cases is limited, this pilot study shows that cathepsin B staining may have a
      prognostic value in transitional cell carcinoma, but more studies are needed for
      a definite conclusion.

PMID- 10210110
TI  - Estimation of oncostatin M (OSM) secretion by peritoneal macrophages with regard
      to the progression of transplantable melanomas.
AB  - The authors have studied the influence of two kinds of transplantable melanomas
      on the secretion of oncostatin M (OSM) and total proteins by peritoneal
      macrophages. Culture supernatant samples were tested by ELISA. The macrophages of
      melanoma-bearing animals released a lower amount of OSM than those of the
      controls. At the same time the results showed statistically significant increase
      of protein content in the supernatants of cultured macrophages from melanoma
      bearing hamsters in comparison with the controls. However, it has not been
      possible to demonstrate any relationship between melanoma progression and changes
      in the secretion of OSM by peritoneal macrophages.

PMID- 10210111
TI  - Very low sensitivity of Wistar:Han female rats to chemocarcinogens in mammary
      carcinogenesis induction.
AB  - Recently a great variability of various mouse and rat strains in the sensitivity
      for mammary tumors induction by means of physical (ionizing radiation) or
      chemical (mostly 7,12-dimethylbenz/a/anthracene, DMBA and N-methyl-N-nitrosourea,
      NMU) initiating agents was noted. The categorization into four groups was
      recommended in rats; the first group with high sensitivity (the incidence of
      tumors practically 100%, the frequency of tumors per entire treated group 2.0),
      the second with average type of sensitivity (incidence below 100%, frequency
      between 1.0-2.0), the third with low sensitivity (frequency 0.3-.4) and the
      fourth with zero sensitivity as the response to single standard dose of DMBA.
      After initial observations we decided to analyze the sensitivity to mammary
      carcinogenesis in the female rats of Wistar:Han strain, used frequently in
      central European region. Twenty mg of DMBA by gavage as single dose, or three
      times 10 mg by gavage as repeated consecutive doses in three-day intervals, or 30
      mg/kg b.w. of NMU intraperitoneally were administered, always between 50-55
      postnatal days (single doses) or between 50-60 days (repeated doses of DMBA). The
      average incidence of mammary tumors did not exceed 10% and the entire group tumor
      frequency was about 0.1 for both carcinogens used. The data allowed us to
      indicate the female Wistar:Han rats as animals with "very low" sensitivity for
      the initiation of mammary tumors by single dose of DMBA or NMU; being in this way
      very close to the insensitive strains. The fact of "sensitivity" improvement to
      higher range after repeated doses of DMBA indicated a non-genetic background of
      the changed sensitivity. Our results support the need to use more then one rat
      strain for initiation of mammary carcinogenesis, and for assessing the bright
      range of the biological response. In this situation the concept of "multi-strain"
      assay seems to be the optimal.

PMID- 10210112
TI  - Comparison of the treatment results in the vulvar and clitoris squamous cell
      carcinoma.
AB  - Treatment results in 360 patients with vulvar carcinoma during the time period
      from 1975 to 1994 were evaluated. Out of the whole group radical vulvectomy with
      bilateral inguinal lymphadenectomy was performed in 215 patients. After excluding
      35 patients having the Stage IV of the disease, 11 with malignant melanoma and 9
      missing, in the group of remaining 160 cases with squamous cell carcinoma the
      survival rates of 3, 5 and 10 years were evaluated. Squamous cell carcinoma
      involvement of the clitoris in 40 patients out of this 160 cases has not
      confirmed clitoris localization as a poor prognostic factor.

PMID- 10210113
TI  - The value of postoperative radiotherapy in advanced renal cell cancer.
AB  - The study reviews experience with the treatment of advanced renal cell cancer at
      Bydgoszcz Regional Cancer Center within a 10-year period from 1985 to 1996. The
      aim of this paper was to evaluate the value of postoperative radiotherapy. The
      medical records of 186 patients with locally advanced renal cell cancer were
      reviewed retrospectively. Postoperative radiation therapy with a median dose of
      50.0 Gy/t was given in 114 patients. The overall and disease-free survival, the
      pattern of recurrences, time interval to recurrence were assessed. For all
      patients, the 5-year overall and disease-free survival rates were 36.2% and
      30.5%, respectively. Non significant difference was observed in terms of 5-year
      overall and disease-free survival between the group of patients with
      postoperative radiotherapy and without, 37.9%/29.5% vs. 35.5%/31.3%,
      respectively. A total of 29 patients (15.6%) developed local recurrences. Local
      failure by stage was as follows: T3N0 without postoperative radiation therapy-
      15.8%, with irradiation--8.8%; T3N(+) without radiation therapy--33.3%, with
      irradiation--33.3%; T4N0 without radiation therapy--33.3%, with irradiation-
      33.3%, T4N(+) without radiation therapy--33.3%, with irradiation--25.0%. 73
      patients (39.3%) had distant metastases as a first symptom of renal cell cancer
      relapse. The median time to relapse for local recurrence or distant metastases
      were approximately two times longer in patients with adjuvant radiotherapy
      compared to those without, 27.0/21.0 months vs. 16.0/12.5 months, respectively.
      In our opinion postoperative radiotherapy reduces the probability of local
      recurrences in selected patients, mainly with pathologic stage T3N0, but its
      impact on survival is minimal.

PMID- 10210114
TI  - On the possible use of a new boron compound, hydroxysalicylhydroxamato
      boron(III), and ultrasound in the treatment of female mice bearing the Ehrlich
      ascites carcinoma cells.
AB  - The inhibitory effects of a new boron compound, hydroxy salicylhydroxamato boron
      (III) (SHB) and ultrasound of frequency 25 KHz (US) on the growth of ascites
      tumor in female Swiss mice were studied by monitoring the survival and the tumor
      growth in the treated tumor bearing mice and also the transplantability and the
      DNA synthesis in the treated tumor (Ehrlich ascites carcinoma) cells. While SHB
      alone produced a highly significant antitumor activity, US alone produced a small
      but significant effect. The combination of SHB and US produced significantly
      greater antitumor activity than SHB alone. The mechanisms of SHB and US actionary
      are discussed.

PMID- 10210115
TI  - Evaluation of the nutritional status and tumor characteristics in premenopausal
      and postmenopausal breast cancer patients.
AB  - Evaluation of the nutritional status, fat tissue distribution, and tumor
      characteristics was carried out in patients with primary breast cancer. The
      patients were classified into two groups according to their menopause:
      premenopausal and postmenopausal. Breast cancer prevalence was considerably
      higher in postmenopausal patients (61%). The patients' nutritional status was
      shown through the body mass index. Based on this indicator, the patients were
      characterized as nonobese and obese. In the premenopausal group, there was no
      significant difference between these categories, whereas the number of obese
      patients was significantly higher (80%) in the postmenopausal group. The analysis
      of tumor parameters as related to menopause and body size did not yield any
      significant differences. However, the estrogen receptor content was significantly
      higher in postmenopausal patients (p < 0.0001). Distribution of fat tissue of the
      android type was higher in obese postmenopausal women than in premenopausal ones
      (77%). The investigation showed that the breast cancer incidence odds are 3.5
      times higher in obese postmenopausal than in premenopausal patients.

PMID- 10210116
TI  - Longitudinal observations in normally grown fetuses with tricuspid valve
      regurgitation: report of 22 cases.
AB  - Longitudinal observations of tricuspid valve regurgitation were prospectively
      performed in 22 singleton fetuses with normal anatomy, normal biometry and normal
      Doppler to determine the characteristics of functional tricuspid valve
      regurgitation. Tricuspid valve regurgitation was semi-quantified by spatial and
      temporal Doppler-derived parameters. In 18 cases tricuspid valve regurgitation
      was part-systolic (early and mid-systolic) and showed little spatial expansion of
      the jet as examined by colour Doppler flow imaging. In 16 of these 18 cases the
      maximum velocity of these regurgitant jets was below 2.00 m/s. Four fetuses
      demonstrated holosystolic regurgitant jets and in addition to the longer duration
      of these jets, the spatial expansion was also greater and the maximum velocity
      was slightly higher compared with the part-systolic tricuspid valve
      regurgitations. Re-examination of the 22 normally grown fetuses showed that
      tricuspid valve regurgitation was a transient phenomenon. Within a period of one
      to seven weeks after the diagnosis of tricuspid valve regurgitation, the
      regurgitation could no longer be demonstrated in any of these cases, including
      the four fetuses with holosystolic regurgitant jets. Tricuspid valve
      regurgitation was the only detected abnormality in all of these cases. The fetal
      outcome of the 22 normally grown fetuses with tricuspid valve regurgitation was
      unremarkable concerning the evaluated parameters. Although fetal tricuspid valve
      regurgitation may be a sign of increased preload, afterload or cardiac
      dysfunction, in most cases tricuspid valve regurgitation is an isolated transient
      phenomenon with little temporal and spatial expansion; nevertheless in some cases
      holosystolic tricuspid valve regurgitation may also be an isolated transient
      finding, and it may be a functional phenomenon.

PMID- 10210117
TI  - Time-related cotyledonary effects of laser coagulation of superficial chorionic
      vessels in an ovine model.
AB  - Endoscopic Nd:YAG laser coagulation of superficial chorionic plate vessels has
      been suggested as a 'causal' therapy for severe twin-to-twin transfusion syndrome
      (TTS), as it is believed to arrest flow over vascular anastomoses. The therapy
      remains debated, partly because it is questioned whether coagulation of
      superficial chorionic vessels can arrest blood flow over deeply located
      anastomoses. The latter are believed to be responsible for the majority of cases
      of severe TTs. In this study, the coagulation performance, and the immediate and
      delayed tissue effects of laser coagulation were evaluated in an in vivo ovine
      model. Eight pregnant ewes of about 100 days' gestational age (term= 145 days)
      were studied. In utero coagulation was done through a 1.2 mm fetoscope loaded
      with a 600 microm laser fibre, connected to an Nd:YAG laser in continuous mode.
      Superficial cotyledonary vessels were coagulated under visual control at a
      distance of 1 cm with a mean power of 60 watts. 31 lasered cotyledons were
      harvested, either immediately (n= 15), 14 days (n = 8) or 42 days (n = 8) after
      the surgery and evaluated by inspection and histology. Control cotyledons were
      either neighbouring cotyledons from the same amniotic sac (internal control) or
      cotyledons from another gestational-age-matched sac (external control). Immediate
      effects consisted of localized coagulation necrosis at the zone of laser impact
      with no significant histological effect at more than 2 mm distance, except tissue
      congestion. Long-term effects consisted of fibrosis without any vascular
      recanalization or tissue regeneration extending from the impact site over the
      whole cotyledon. All treated cotyledons underwent complete infarction over time.
      This study provides experimental evidence supporting that laser coagulation of
      superficial chorionic vessels entering a cotyledon achieves complete functional
      elimination of the involved cotyledon.

PMID- 10210118
TI  - Ultrasound measurements of the diameter of the fetal trachea, larynx and pharynx
      throughout gestation applicability to prenatal diagnosis of obstructive anomalies
      of the upper respiratory-digestive tract.
AB  - The purpose of the present study was to obtain normative data for the fetal upper
      respiratory tract by using high-resolution ultrasound techniques. Furthermore, we
      wanted to test the potential utility of the resulting normograms in diagnosing
      obstructive lesions of the trachea and oesophagus. Sonographic measurements of
      the diameters of the trachea, larynx and pharynx were obtained at well-defined
      planes from a prospective cross-sectional sample of 198 normal patients of known
      gestational age between 15 and 40 weeks' gestation. All measurements were
      performed during fetal apnea and in the absence of swallowing. The same
      measurements were also obtained from two cases with laryngeal atresia and three
      cases with oesophageal atresia, all of which were diagnosed prenatally. The data
      obtained were plotted on the constructed normograms. In normal fetuses
      approximately linear relationships existed between tracheal, laryngeal and
      pharyngeal diameter, on the one hand, and gestational age, on the other, with the
      measurements correlating significantly (p<0.0001) with gestational age. The
      linear regression coefficients (r2) for the tracheal, laryngeal and pharyngeal
      diameters were 0.66, 0.55 and 0.32, respectively. The 95 per cent prediction
      limits were also calculated. In fetuses with laryngeal atresia only the tracheal
      diameter was significantly higher as compared with that of normal fetuses. Data
      of the fetuses with oesophageal atresia showed that there were no changes in the
      upper airway anatomy. Our study provides normative data for the upper respiratory
      tract. In the prenatal diagnosis of obstructive neck anomalies the usefulness of
      the data would seem to be limited to those affecting the respiratory tract. Among
      the structures measured, only the trachea may prove to be of clinical
      significance.

PMID- 10210119
TI  - Clinical follow-up of high mid-trimester maternal serum intact human chorionic
      gonadotrophin concentrations in singleton pregnancies.
AB  - Mid-trimester biochemical screening of 38 143 pregnancies in south-east Scotland
      revealed 127 cases (0.34 per cent) in which the maternal serum (MS) intact human
      chorionic gonadotrophin (hCG) concentration was > or = 4 multiples of the median
      in singleton pregnancies (MOM). Three were lost to follow-up but in 72 (58 per
      cent) complications developed or there were associated fetal abnormalities. This
      percentage was greatest at very high hCG concentrations, 92 per cent with hCG >
      or = 10 MOM (n = 12) compared with 48 per cent with hCG concentrations of 4-4.99
      MOM (n=69). 22 cases had an MS alpha-fetoprotein > or = 2 MOM in addition to an
      MS hCG > or = 4 MOM, and in only 3 of these was the pregnancy uneventful; 86 per
      cent were associated with abnormalities or pregnancy complications.

PMID- 10210120
TI  - Heat stable and urea resistant alkaline phosphatase in maternal neutrophils from
      normal and Down syndrome pregnancies.
AB  - Activity levels of total and placental alkaline phosphatase (AP) were determined
      in maternal serum and neutrophils of normal and Down syndrome pregnancies. The
      placental iso-enzyme (PAP) was identified by its relative stability to urea and
      heat. Significant increase in the activity of all iso-enzymes across gestational
      stages was observed in maternal sera of 28 normal pregnancies. However, in the
      neutrophil extracts of the same blood samples no differences were detected
      between trimesters. Another set of experiments was aimed at finding diagnostic
      differences of PAP activity in maternal neutrophils of normal and trisomy 21
      affected pregnancies. No differences of heat stable AP activity were found in
      maternal samples of 19 normal and 19 Down syndrome affected pregnancies. Urea
      resistant AP proportions were also similar when measured after 40 minutes of
      exposure (13 samples in each group). However, a marginally significant increase
      was observed in the mean value of the Down syndrome affected samples, after 60
      minutes of urea treatment. In view of the above results we conclude that
      neutrophil AP activity is not as yet a useful marker for the screening of trisomy
      21 fetuses.

PMID- 10210121
TI  - Fetal lactic dehydrogenase variation in normal pregnancy and in cases of severe
      intra-uterine growth restriction.
AB  - Physiological and pathological fetal levels of lactic dehydrogenase (LDH),
      including its five different iso-enzymes are still poorly known. Our objectives
      were to compare total LDH levels and its five iso-enzymes between a control group
      of healthy fetuses and a group of fetuses with severe intra-uterine growth
      restriction (IUGR), and to determine the biochemical associations and the
      prognostic value of elevated LDH activity in fetuses with IUGR. Total LDH levels,
      haematologic values and liver enzyme activities were measured in 108 healthy
      fetuses from 17 to 37 weeks of gestation and in 44 fetuses with severe IUGR.
      Total fetal LDH in plasma from the healthy fetuses were constant throughout
      pregnancy (mean (SD)= 305.09 (46.97)). Total LDH values in plasma significantly
      increased in cases of IUGR (p=0.003), and the degree of increase was
      significantly correlated with fetal erythroblastosis (n =44, r=0.80, p<0.001).
      LDH 5 significantly decreased in the IUGR group (p=0.03). Total LDH values
      strictly above 400 IU/l (a value equal to the mean+2 SD in the healthy fetus
      group) were found to be significantly associated with thrombocytopenia (p<0.001),
      erythroblastosis (p=0.008) and an increase in AST value (p=0.03). These results
      suggest that the fetal LDH value in plasma is a useful biological marker for
      severe chronic distress.

PMID- 10210122
TI  - Amniocentesis or chorionic villus sampling in multiple gestations? Experience
      with 500 cases.
AB  - 500 women with multiple pregnancies underwent amniocentesis or chorionic villus
      (CV) sampling at our department between January 1988 and July 1997. The aim of
      this retrospective study was to evaluate the laboratory aspects and the
      consequences of discordant results in these pregnancies in relation to the method
      of sampling. Uncertain results in one or both samples, requiring further
      investigation were more frequent in CV samples (eight times in 163 paired
      samples, 5 per cent) than in amniotic fluid (AF) samples (once in 298 paired
      samples, 0.3 per cent). Sampling one fetus twice (erroneous sampling) was seen
      only once among 163 pregnancies with two CV samples in our study. Cross
      contamination due to mixed sampling was discovered in two of seven pregnancies
      that underwent DNA diagnosis in CV and might be a rather regular occuring
      phenomenon. In none of the 500 pregnancies mixed sampling caused diagnostic
      dilemmas. A third sampling problem, maternal cell contamination caused a
      diagnostic problem once among the AF samples. Selective fetal reduction appeared
      safer after CV sampling than after amniocentesis. Subsequently, CV sampling
      instead of amniocentesis has become the method of choice for prenatal diagnosis
      in multiple pregnancies in our department.

PMID- 10210123
TI  - Elevated maternal age-specific rates of Down syndrome liveborn offspring of women
      of Mexican and Central American origin in California.
AB  - BACKGROUND: Maternal age-specific rates of Down syndrome livebirths are widely
      utilized in personal and policy decisions concerning provision of and election of
      prenatal cytogenetic diagnostic services. The only extensive reference data
      available are on those of primarily European ancestral origin. In the absence of
      definitive evidence of any ethnic, racial or environmental influence upon rates
      (other than those associated with age) these rate schedules have been widely
      applied to those of all national origins. METHODS: Available material age
      specific data on livebirths from intensive studies on those of Hispanic
      (primarily of Mexican and Central American background) and of other origin in
      populations in the U.S.A. with likely complete ascertainment were analysed. The
      numbers observed were compared with (i) those predicted from established
      published rate schedules in those of primarily European origin, and (ii) with the
      observations on livebirths of non-Hispanic European origin in the same population
      as the Hispanic live births. RESULTS: In comparisons with the numbers predicted
      from published rates, observed numbers of case among Hispanic live births were
      increased by 19 per cent (SE 0.06) in younger mothers, 23 per cent in older
      mothers (SE 0.07) and 20 per cent (SE 0.04) in those of all ages. Comparisons
      with observed rates in those of Hispanic origin with those observed in non
      Hispanic births in the same time intervals and populations indicated that the
      excess rates in Hispanics were not attributable to some local factor increasing
      rates in all ethnic groups at least among those under 35. CONCLUSIONS: Data on
      mothers of Mexican and Central American origin residing in the U.S.A. indicate
      maternal age-specific rates of Down syndrome in live births about 20 per cent
      greater than those in published rate schedules on Down syndrome, widely used in
      decisions concerning election or provison of prenatal diagnostic services. The
      reason for this difference remains unknown.

PMID- 10210124
TI  - Prenatal diagnosis of mucolipidosis II--electron microscopy and biochemical
      evaluation.
AB  - Prenatal diagnosis of mucolipidosis type II (I-cell disease) can be performed
      quickly and reliably by electron microscopy of chorionic villus tissue. This
      study reports the results of studies in three prenatal assessments (two families)
      where the pregnancy was at one in four risk of the disorder. In all three cases,
      electron microscopy showed marked vacuolation in chorionic villus cells,
      consistent with the fetus being affected by the disorder. Further studies in
      cultured chorionic villus cells showed a marked deficiency of a number of
      lysosomal enzymes. All pregnancies were terminated. Follow-up studies in fetal
      tissue (where available) confirmed the prenatal diagnosis as correct.

PMID- 10210125
TI  - Sex chromosome pentasomy (49,XXXXY) presenting as cystic hygroma at 16 weeks'
      gestation.
AB  - The pentasomy 49,XXXXY is one of the rarest sex chromosome defects, occurring
      with an estimated incidence of 1 in 85 000 male births. This condition is
      associated with pre- and postnatal growth deficiency, severe mental retardation,
      hypogenitalism, and other skeletal, facial and cardio-vascular anomalies. In this
      report we present such a case diagnosed prenatally by chorionic villus sampling
      after the ultrasound detection of cystic hygroma at 16 weeks' gestation. Although
      the prenatal diagnosis of cystic hygroma and its association with aneuploidy has
      been documented in numerous reports, sex chromosome aneuploidy, other than the
      45,X karyotype, accounts for only 0.3 per cent of cases.

PMID- 10210126
TI  - Prenatal detection of a tetralogy of Fallot with origin of the left pulmonary
      artery from the ascending aorta in a familial 22q11 microdeletion.
AB  - Here we report a case of prenatal diagnosis of anomalous origin of the left
      pulmonary artery from the ascending aorta associated with a tetralogy of Fallot
      in a familial form of 22q11 deletion. The mother, who had a normal heart and a
      velo-cardio-facial syndrome, had a first child with a pulmonary atresia plus
      ventricular septal defect associated with a 22q11 deletion. Prenatal diagnosis
      during the second pregnancy identified the above-described cono-truncal anomaly
      and FISH study showed a recurrent 22q11 deletion. This case illustrates the
      intrafamilial variability of cardiac involvement in 22q11 deletion as well as the
      possibility of diagnosing complex cono-truncal malformations during fetal life.

PMID- 10210127
TI  - Trisomy 17 mosaicism in amniotic fluid cells not found at birth in blood but
      present in skin fibroblasts.
AB  - This article describes a case of fetal trisomy 17 mosaicism found in amniotic
      fluid cells in one of two bichorial biamniotic twins without any sonographic
      anomaly. The extra chromosome 17 was absent from cord blood cells at birth but
      present on karyotype and in situ hybridization in cultured fibroblasts from skin
      biopsy. Clinical examination showed a few mild dysmorphic features and a moderate
      neurological involvement which may rather be related to prematurity. It therefore
      seemed important to obtain the karyotype on fibroblasts when a trisomic cell line
      was found in amniocentesis and not confirmed on blood lymphocytes, even in the
      absence of dysmorphic features. This should help to differentiate a real mosaic
      from a mosaic restricted to extra-fetal tissues.

PMID- 10210128
TI  - Prenatal diagnosis by FISH in a family with Pelizaeus-Merzbacher disease caused
      by duplication of PLP gene.
AB  - A diagnosis of Pelizaeus-Merzbacher disease (MIM 312080) was made in a young boy.
      No mutation in the coding region of the proteolipid protein (PLP) gene had been
      found. The boy's maternal aunt came for prenatal diagnosis when 16+ weeks
      pregnant and carrying a male fetus. Samples were tested for duplication of the
      PLP gene, by interphase FISH, in lymphocyte preparations from the proband, his
      aunt and an amniotic fluid cell preparation from the fetus. The proband was found
      to carry the duplication, thus confirming the diagnosis of Pelizaeus Merzbacher
      disease, but neither the aunt nor the fetus carried a duplication.

PMID- 10210129
TI  - Prenatal diagnosis of Lowe syndrome by OCRL1 messenger RNA analysis.
AB  - Prenatal screening of oculo-cerebro-renal syndrome of Lowe (OCRL; McKusick
      309000) was performed using cultured amniocytes. Following identification of
      defective mRNA expression in the OCRL; gene of the proband's fibroblasts, the
      mRNA size and quantity of the cultured amniocytes were compared. Based on this
      analysis, the fetus was diagnosed as being normal and was subsequently delivered
      as a healthy boy. This is the first reported successful prenatal screening of
      OCRL using a comparison with defective mRNA of OCRL1 from affected subjects.

PMID- 10210130
TI  - Detection of fetal-specific DNA after enrichment for trophoblasts using the
      monoclonal antibody LK26 in model systems but failure to demonstrate fetal DNA in
      maternal peripheral blood.
AB  - Trophoblast cells can be detected in maternal blood during normal human pregnancy
      and DNA from these cells may be used for non-invasive prenatal diagnosis of
      inherited diseases. The possibility of enriching trophoblast cells from maternal
      blood samples using a monoclonal antibody (LK26) against a folate-binding
      protein, which recognizes trophoblast in normal tissues, in conjunction with
      immunomagnetic cell sorting was investigated. Verification of the presence of
      fetal DNA in the sorted samples was done by detection of fetal/paternal-specific
      short tandem repeat (STR) alleles using polymerase chain reaction (PCR) and
      automated fluorescence-based genotyping. After successful initial experiments
      using retroplacental blood samples with a high number of trophoblast cells or an
      artificial mixture of trophoblast cells and blood, several versions of the
      enrichment method were attempted on peripheral maternal blood samples. However,
      it was not possible to detect fetal DNA sequences in these samples, most probably
      due to the extremely low number of trophoblast cells. Positive identification and
      retrieval of trophoblast cells in suspension or trophoblast nuclear material
      prepared on microscope slides after cell sorting procedures can be a solution to
      this problem.

PMID- 10210131
TI  - Hydrolethalus syndrome in a non-Finnish family: confirmation of the entity and
      early prenatal diagnosis.
AB  - We present a family in which the first affected child presented with a 'milder'
      form of the hydrolethalus syndrome and survived to seven months, and two
      subsequent pregnancies with typical features detected early by ultrasound
      evaluation. We propose that the 'milder' cases are indeed true cases of the
      hydrolethalus syndrome and that allelic variability may be responsible for these
      'non-typically Finnish' findings. We also demonstrate that, especially in
      families where there has been a previously affected fetus, echographic diagnosis
      can be made in the first trimester, as early as the 11th week of gestation.

PMID- 10210132
TI  - Prenatal diagnosis of a satellited non-acrocentric chromosome derived from a
      maternal translocation (10;13)(p13;p12) and review of literature.
AB  - We identified a familial balanced translocation involving chromosomes 10 and 13
      through the finding of a satellited 10p chromosome in a fetus. The phenotype of
      two unbalanced products of the translocation resulting in pure monosomy 10p13 and
      trisomy 10p13 is described. This familial case and two of our unreported cases
      are discussed in the light of other prenatal observations with satellited non
      acrocentric chromosomes reported in the literature.

PMID- 10210133
TI  - Prenatal diagnosis of nail-patella syndrome.

PMID- 10210134
TI  - Primary fetal hydrothorax with lymphangiectasia, pulmonary situs inversus and
      abnormal tracheo-bronchial tree.

PMID- 10210135
TI  - Regression curves for maternal serum inhibin A.

PMID- 10210136
TI  - Current awareness in prenatal diagnosis.

PMID- 10210137
TI  - Cytokine and chemokine: a stimulating couple.

PMID- 10210138
TI  - Adenoviral vectors expressing lymphotactin and interleukin 2 or lymphotactin and
      interleukin 12 synergize to facilitate tumor regression in murine breast cancer
      models.
AB  - We have previously demonstrated that intratumoral injection with Ad vectors
      expressing IL-2 or IL-12 can induce regression in a murine breast cancer model.
      These IL-2- or IL-12-induced antitumor responses were mainly mediated by Ag
      specific T cells. Lymphotactin is a novel lymphocyte chemokine that can cause
      local accumulation of CD4+, CD8+, and NK cells. We hypothesized that addition of
      lymphotactin may enhance the antitumor immune responses induced by locally
      produced IL-2 and IL-12 as we have previously shown. To this end we constructed
      two double-recombinant adenoviral vectors expressing lymphotactin along with
      either IL-2 (Ad5 Lym/IL-2) or IL-12 (Ad5 Lym/IL-12). Subcutaneous injection of
      polyoma middle T (PyMT) or Neu (8142) transgenically derived breast
      adenocarcinoma cells, in the hind flank of FVB/n mice, results in the formation
      of tumor nodules in 14-21 days. We show that these constructs elicit potent
      antitumor responses when administered intratumorally. The antitumor responses are
      long lasting as determined by rechallenge experiments and hence demonstrate a
      protective immunity. These observations indicate that by augmenting the antitumor
      response with adenoviral vectors expressing lymphotactin in combination with IL-2
      or IL-12 is a novel way to enhance immunotherapeutic approaches.

PMID- 10210139
TI  - Early cell loss after angioplasty results in a disproportionate decrease in
      percutaneous gene transfer to the vessel wall.
AB  - Acute cell loss has been documented following angioplasty of normal rat and
      rabbit arteries. Here we analyzed the effects of balloon injury intensity on
      early cellular loss in single- and double-injury models and how it influences the
      efficiency of percutaneous gene delivery to the vessel wall. Rabbits underwent
      bilateral iliac angioplasties (n = 52) with 2.5-mm (balloon-to-artery [B/A]
      ratio, 1.08 to 1.13) and 3.0-mm (B/A ratio, 1.29 to 1.34) balloons. In the single
      injury model, the 3.0-mm balloon induced a 61% reduction in medial cellularity at
      3 days postinjury (p < 0.001) while the 2.5-mm balloon did not produce
      significant cell loss. In the double-injury model, the effects were more
      pronounced, with 35% (p < 0.01) and 91% (p < 0.001) reductions in medial
      cellularity at 3 days with the 2.5- and 3.0-mm balloons, respectively, but
      neointimal cellularity was decreased only with the 3.0-mm balloon (37% reduction,
      p = 0.025). Adenovirus-mediated beta-galactosidase gene delivery with a channel
      balloon (n = 24) revealed that larger balloon-to-artery ratios decreased both
      absolute levels and relative frequencies of transgene expression in the vessel
      wall. In the single-injury model, gene transfer efficiency was 4.2+/-1.1 and
      1.3+/-0.25% (p < 0.05) for the small and large balloons, respectively. In the
      double-injury model, gene transfer efficiency was 6.6+/-1.6 and 2.3+/-0.8% (p <
      0.05) in the neointima and 4.1+/-1.2 and 2.6+/-1.2% (p = NS) in the media for the
      small and large balloon, respectively. We conclude that early cell loss is
      dependent on the intensity of the injury in both single- and double-injury models
      of balloon angioplasty, with greater frequencies of cell loss occurring in the
      media than in the neointima. In both models, larger balloon-to-artery ratios
      result in disproportionate reductions in percutaneous adenovirus-mediated gene
      delivery.

PMID- 10210140
TI  - Intratracheal administration of interleukin 12 plasmid-cationic lipid complexes
      inhibits murine lung metastases.
AB  - Administration of plasmid/lipid complexes to the lung airways for the treatment
      of metastatic pulmonary diseases represents a new strategy of gene therapy. In
      this study we present evidence that intratracheal administration of a plasmid
      encoding murine IL-12 complexed with N-[1-(2,3-dioleyloxy)propyl)-N,N,N
      trimethylammonium chloride:cholesterol inhibits the growth of lung metastases,
      using a renal cell carcinoma model. Instillation of pIL-12/lipid complexes
      resulted in expression of biologically active IL-12 (170-240 pg/ml) and IFN-gamma
      (100-190 pg/ml) in the bronchoalveolar lavage fluid. A significantly reduced
      number of lung metastases (26+/-24) was observed in mice instilled with IL
      12/lipid complexes 24 hr after tumor challenge, whereas more than 250 metastatic
      foci were counted in lungs of untreated mice. Moreover, IL-12/lipid inhibited the
      growth of 3-day-old established metastases when compared with empty plasmid/lipid
      or IL-12 plasmid in saline. Mice receiving IL-12 gene therapy survived
      significantly longer (median survival of 43 days) than untreated mice (median
      survival of 31 days) or mice treated with control plasmid/lipid complexes (median
      survival of 35 days). These data demonstrate that a nonviral IL-12 gene therapy
      employing synthetic cationic lipids as a delivery system can be used to inhibit
      the development of lung metastases. Thus, this method provides support for the
      use of IL-12/lipid complexes to control the growth of pulmonary metastases and
      represents a potentially safer alternative to IL-12 protein immunotherapy.

PMID- 10210141
TI  - Molecular evaluation of biopsy and autopsy specimens from patients receiving in
      vivo retroviral gene therapy.
AB  - We used the polymerase chain reaction (PCR) to assay for the presence of
      retroviral vector and replication-competent retrovirus (RCR) in autopsy and
      biopsy specimens from patients who received inoculations of retroviral vector
      producer cells (VPCs) into brain tumors or apparently normal tissues surrounding
      resected tumors. The PCR assays were capable of detecting 1 or more proviral
      copies of vector or RCR in 500,000 cells. Of 113 patients treated in clinical
      trials between 1994 and 1997, autopsy specimens were available from 32 patients.
      Brain tumor biopsies were also available from 24 patients. A total of 346
      specimens was analyzed. Vector DNA was detected in 55% of tumor samples and 22%
      of brain samples obtained from resection margins. In contrast, most of the
      nonbrain tissues were negative for vector DNA; only low levels (<0.03%) of vector
      sequence were detected in 6 of 240 (2.5%) nonbrain tissues. Vector DNA was not
      detected in gonadal tissues from 12 men and 10 women. More importantly, RCR was
      not detected in any of the 134 biopsy and autopsy tissues tested, including all
      brain tumor, brain, and gonadal specimens. These results comprise the largest
      data set on molecular analysis of autopsy specimens from patients receiving
      retroviral gene therapy and indicate that distribution of retroviral vectors
      following injection of high doses of VPCs is limited to the site of inoculation.

PMID- 10210142
TI  - Plasmid DNA malaria vaccine: tissue distribution and safety studies in mice and
      rabbits.
AB  - To evaluate the safety of a plasmid DNA vaccine, tissue distribution studies in
      mice and safety studies in mice and rabbits were conducted with VCL-2510, a
      plasmid DNA encoding the gene for the malaria circumsporozoite protein from
      Plasmodium falciparum (PfCSP). After intramuscular administration, VCL-2510
      plasmid DNA was detected initially in all of the highly vascularized tissues, but
      at later time points was found primarily in the muscle at the site of injection,
      where it persisted for up to 8 weeks. After intravenous administration, plasmid
      DNA initially distributed at a relatively low frequency to all the tissues
      examined except the gonads and brain. However, plasmid DNA rapidly cleared, and
      by 4 weeks postadministration could be detected only in the lung of one of six
      animals evaluated. In a safety study in mice, eight repeated intramuscular
      injections of VCL-2510 at plasmid DNA doses of 1, 10, and 100 microg had no
      adverse effects on clinical chemistry or hematology, and did not result in any
      organ pathology or systemic toxicity. In a safety study in rabbits, six repeated
      intramuscular injections of VCL-2510 at plasmid DNA doses of 0.15 and 0.45 mg had
      no discernible effects on clinical chemistry, hematology, or histopathology. No
      evidence of autoimmune-mediated pathology, anti-nuclear antibodies (ANA), or
      antibodies to dsDNA were observed in the mouse or rabbit studies.

PMID- 10210143
TI  - Plasmid DNA malaria vaccine: the potential for genomic integration after
      intramuscular injection.
AB  - Plasmid-based (naked DNA) genetic vaccines are now entering clinical trials to
      test their safety and efficacy in healthy human volunteers. A safety concern
      unique to this new class of vaccines is the potential risk of deleterious
      integration into host cell genomic DNA following direct intramuscular injection.
      To address this issue experimentally, a preclinical safety study was conducted in
      mice to determine the structural nature of plasmid DNA sequences persisting in
      total muscle DNA at both 30 and 60 days following a single intramuscular
      injection of a plasmid expressing the Plasmodium falciparum circumsporozoite
      protein. In a protocol described for the first time, total DNA was extracted from
      muscle tissue and was subsequently linearized with a restriction endonuclease to
      enable agarose gel size fractionation of all extrachromosomal plasmid DNAs from
      high molecular weight mouse genomic DNA. Using PCR assays to quantitate plasmid
      specific sequences, it was found that the amount of plasmid DNA persisting in
      muscle tissue varied but averaged about 10 fg per microgram of genomic DNA (in
      the range of 1500 copies per 150,000 genomes). In two of four separate
      experimental injections of mouse muscle, PCR assays of genomic DNA fractions
      indicated that agarose gel purification removed plasmid DNA down to a level of <
      or =3 copies per 150,000 mouse genomes. In the two other experimental samples, 3
      30 copies of plasmid DNA remained associated with purified genomic DNA. The time
      following injection (i.e., 30 or 60 days) was not a factor in the number of
      copies of plasmid associating with genomic DNA and it was not possible to
      conclude if such sequences were covalently linked to genomic DNA or simply
      adventitiously associated with the genomic DNA. However, if an assumption is made
      that the highest level plasmid DNA found associated with genomic DNA (i.e., 30
      copies) represented covalently integrated plasmid inserts and that each insert
      resulted in a mutational event, the calculated rate of mutation would be 3000
      times less than the spontaneous mutation rate for mammalian genomes. This level
      of integration, if it should occur, was not considered to pose a significant
      safety concern.

PMID- 10210144
TI  - Inner ear transgene expression after adenoviral vector inoculation in the
      endolymphatic sac.
AB  - Gene transfer has been performed in a variety of organs. In the mammalian inner
      ear, viral vectors have been used to introduce exogenous reporter genes via the
      scala tympani into the cochlea. While scala tympani inoculation is clinically
      feasible, it is not without risks. Moreover, transgene expression has so far been
      restricted to the cochlear tissues in the perilymphatic spaces that are
      contiguous with the scala tympani. To achieve gene transfer of vestibular organs
      and cells surrounding the endolymphatic space, and to extend the clinical utility
      of inner ear gene therapy, we developed a new surgical approach for vector
      inoculation. A replication-deficient adenoviral vector, Ad.RSVntlacZ, was
      injected into the guinea pig endolymphatic sac. A large number of blue (LacZ
      positive) cells was observed in the endolymphatic sac and duct, the vestibule,
      and the ampulla. Blue cells were also detected in the cochlea, mainly in cells
      bordering the endolymphatic space: marginal cells in the stria vascularis and
      supporting cells in the organ of Corti. These findings indicate that inoculation
      of viral vectors into the endolymphatic sac can provide efficient gene transfer
      into a variety of cell types that are not accessible via scala tympani
      inoculation.

PMID- 10210145
TI  - Efficient gene delivery into human dendritic cells by adenovirus polyethylenimine
      and mannose polyethylenimine transfection.
AB  - Gene-modified human dendritic cells (DCs) were generated by transfection with
      adenovirus polyethylenimine DNA (Ad/PEI/DNA) and mannose polyethylenimine DNA
      (ManPEI/DNA) complexes. Ad/PEI/DNA complexes have plasmid DNA bound to adenovirus
      particles by PEI and deliver DNA into cells via the adenovirus infection route.
      Such transfection complexes yield high transduction levels and sustained
      expression of luciferase and green fluorescent protein reporter genes and were
      almost as effective as recombinant adenovirus vectors. ManPEI/DNA complexes rely
      on uptake by receptor-mediated endocytosis via mannose receptor, which is highly
      expressed on DCs. While gene delivery by ManPEI/DNA complexes was less efficient
      than by Ad/PEI transfection, incorporation of adenovirus particles in ManPEI/DNA
      transfection complexes further enhanced transduction efficiencies and transgene
      expression. We also demonstrate that Ad/PEI-transfected DCs are competent in
      stimulating T cell proliferation in allogeneic and autologous mixed lymphocyte
      reactions, and in activating T cells from T cell receptor (TCR)-transgenic mice
      in an antigen-specific manner. Thus, the present study establishes the following
      relative order of transduction efficiencies of viral and nonviral gene delivery
      systems for primary human DCs: recombinant adenovirus > Ad/PEI = Ad/ManPEI >
      ManPEI > PEI. Ad/PEI and ManPEI transfection modes represent particularly
      versatile transduction systems for DCs, with ManPEI being built up exclusively of
      synthetic compounds.

PMID- 10210146
TI  - Modulation of cell-mediated immunity prolongs adenovirus-mediated transgene
      expression in sciatic nerve.
AB  - In a previous report, we demonstrated that a first-generation (E1- and E3
      deleted) recombinant adenovirus can transduce expression of the E. coli lacZ gene
      into Schwann cells, both in vitro and in vivo, suggesting that this method might
      be useful for future therapy of peripheral neuropathy, including CMT1. Adenovirus
      mediated gene transfer was limited, however, by demyelination and Wallerian
      degeneration at the site of virus injection, as well as by attenuation of viral
      transgene expression over time. In our current work we have optimized adenoviral
      vector-mediated transgene expression after intraneural injection into sciatic
      nerve. Using an improved injection protocol, peak expression of lacZ occurs
      between 10 and 14 days after injection of 2-week-old rats, decreases thereafter,
      and there is minimal associated tissue injury. In contrast, few lacZ-expressing
      Schwann cells are found in nerve of adult animals 10 days after injection,
      probably owing to immune clearance of virus-infected cells. Consistent with this
      notion, high levels of LacZ are found in sciatic nerve 30 days after injection of
      adult SCID mice, which have a genetic defect in both cellular and humoral
      immunity, of adult beta2-microglobulin-deficient mice (beta2M4-/-), which have a
      genetic defect in cellular immunity, or of adult mice treated with the
      immunosuppressing agent FK506. In addition, adenovirus-infected Schwann cells
      cocultured with axons in vitro, in the absence of a host immune response,
      ensheathe axons and express lacZ for at least 8 weeks. These data thus
      demonstrate that lacZ transgene expression of first-generation recombinant
      adenovirus in sciatic nerve in adult mice, as in other tissues, is limited mainly
      by the host cellular immune response to the virus, which can be overcome by
      attenuation of host cell-mediated immunity. Adenoviral vectors might thus be used
      to modulate Schwann cell gene expression in patients with peripheral neuropathy
      after appropriate immunosuppression.

PMID- 10210147
TI  - Retrovirus-mediated gene transfer of the human multidrug resistance-associated
      protein into hematopoietic cells protects mice from chemotherapy-induced
      leukopenia.
AB  - Utilization of chemotherapy for the treatment of tumors is mainly limited by its
      hematological toxicity. Because of the low-level expression of drug resistance
      genes, transduction of hematopoietic progenitors with multidrug resistance 1
      (MDR1) or multidrug resistance-associated protein (MRP) genes should provide
      protection from chemotherapeutic agent toxicity. Successful transfer of drug
      resistance genes into hematopoietic cells may allow the administration of higher
      doses of chemotherapy and, thus, increase regression of chemosensitive tumors.
      The interest in the use of MRP as an alternative to MDR1 for bone marrow
      protection lies in its different modulation. This would allow, in the same
      patient, the use of MDR1 reversal agents to decrease MDR1 tumor resistance
      without reversing bone marrow (BM) protection of the MRP-transduced hematopoietic
      cells, since MRP expression is not reversed by these agents. We have constructed
      MRP-containing retroviral vectors using the phosphoglycerate kinase promoter and
      generated ecotropic producer cells. Lethally irradiated mice were engrafted with
      BM cells transduced by coculture with MRP producer cells. Evidence of long-term
      (9 months) gene transfer was provided by PCR of peripheral blood from MRP
      transduced mice. Southern blot analysis confirmed the integrity of the provirus
      in the MRP-transduced mice. Long-term MRP expression (>5 months) was detected by
      RT-PCR and fluorescence-activated cell sorting of blood from living mice. High
      level expression of MRP in murine hematopoietic cells reduces doxorubicin-induced
      leukopenia and mortality. Furthermore, we show in vivo selection of MRP
      transduced cells following doxorubicin administration, with better and more
      significant chemoprotection after the second chemotherapy cycle. These data
      indicate that MRP retroviral gene transfer may be useful for chemoprotection and
      selection.

PMID- 10210149
TI  - Successful culture and sustainability in vivo of gene-modified human oral mucosal
      epithelium.
AB  - Human oral mucosal cells are an attractive site for tissue engineering because
      they are the most accessible cells in the body and easy to manipulate in vitro.
      They thus have possibilities for targeting by somatic gene therapy. We examined
      the efficiency of retrovirus-mediated gene transfer and the construction of
      mucosal epithelium in vivo. Human oral mucosal cells were transduced with a
      retroviral vector carrying the lacZ gene at high efficiency and constructed
      epithelium after G418 selection with 3T3 cells in vitro. The cultured oral
      mucosal epithelium membrane was then grafted onto immunodeficient mice. Beta-Gal
      expression was detected histochemically in vivo 5 weeks after grafting.
      Furthermore, we transduced factor IX cDNA into the mucosal epithelium membrane,
      and it was then transplanted into nude mice. Between 0.6 and 1.8 ng of human
      factor IX per milliliter was found in mouse plasma, and the production was
      continued for 23 days in vivo. These results confirmed that the oral mucosal
      epithelium is an ideal target tissue for gene therapy or tissue engineering.

PMID- 10210148
TI  - Hair cell protection from aminoglycoside ototoxicity by adenovirus-mediated
      overexpression of glial cell line-derived neurotrophic factor.
AB  - Aminoglycosides are commonly used antimicrobial drugs that often have ototoxic
      side effects. The ototoxicity often involves permanent loss of cochlear hair
      cells (HCs). Neurotrophic factors have been shown to protect a variety of
      tissues, including HCs, from toxic trauma. To determine if glial cell line
      derived neurotrophic factor (GDNF) can protect cochlear HCs from trauma, we
      inoculated an adenoviral vector encoding the human GDNF gene into guinea pig
      cochleae via the round window membrane 4 days prior to injection of
      aminoglycosides. Control groups showed little or no negative influence of the
      viral inoculation on cochlear structure and function. In contrast, ears that were
      inoculated with the GDNF vector had better hearing and fewer missing HCs after
      exposure to the ototoxins, as compared with controls. Our results demonstrate the
      feasibility of gene therapy for cochlear application and suggest that virus
      mediated overexpression of GDNF may be developed as a valuable prevention against
      trauma-induced HC death.

PMID- 10210150
TI  - Role of caspase-3 and nitric oxide synthase-2 in gastric mucosal injury induced
      by indomethacin: effect of sucralfate.
AB  - BACKGROUND: Apoptosis is the process of programmed cell death characterized by a
      series of distinct biochemical and morphological changes which involve activation
      of caspase proteases cascade that remains under the regulatory control of nitric
      oxide. Here, we investigated the activity of a key apoptotic protease, caspase-3,
      and the expression of inducible nitric oxide synthase (NOS-2) and tumor necrosis
      factor-alpha (TNF-alpha) associated with gastric epithelial cells apoptosis
      during indomethacin-induced gastric mucosal injury, and evaluated the effect of
      antiulcer agent sucralfate on this process. METHODS: The experiments were
      conducted with groups of rats pretreated intragastrically with 200 mg/kg
      sucralfate or the vehicle, followed 30 min later by an intragastric dose of
      indomethacin at 60 mg/kg. The animals were killed 2 h later and their gastric
      mucosal tissue used for macroscopic assessment, assays of epithelial cells
      apoptosis and TNF-alpha, and the measurements of caspase-3 and NOS-2 activities.
      RESULTS: In the absence of sucralfate, indomethacin caused multiple hemorrhagic
      lesions occupying 29.3 mm2 of the corpus area, and accompanied by a 20-fold
      enhancement in gastric epithelial cells apoptosis and a 47% increase in mucosal
      expression of TNF-alpha, while NOS-2 showed an 11.9-fold induction and the
      activity of caspase-3 increased 3.9-fold. Pretreatment with sucralfate produced a
      59.7% reduction in the extent of mucosal damage caused by indomethacin, a 41.2%
      decrease in the epithelial cells apoptosis and a 33.4% reduction in TNF-alpha,
      while the activity of caspase-3 decreased by 45% and that of NOS-2 showed a 44.7%
      decline. CONCLUSIONS: The results implicate caspase-3 in the process of
      indomethacin-induced gastric epithelial cells apoptosis, and point towards
      participation of NOS-2 in the amplification of the cell death signaling cascade.
      Our findings also show that sucralfate protection against gastric mucosal injury
      caused by indomethacin involves the suppression of NOS-2 and the apoptotic events
      propagated by caspase-3.

PMID- 10210151
TI  - Role of mast cells as a trigger of inflammation in Helicobacter pylori infection.
AB  - Helicobacter pylori (H. pylori) induces severe inflammation and plays a key role
      in gastric mucosal diseases. In general, mast cells have been believed to play an
      important role in inflammation. Although mast cells were detected in the gastric
      mucosa, the role of mast cells in the gastric mucosal inflammation caused by H.
      pylori is still unclear. Therefore, we examined the effects of H. pylori water
      extract on the degranulation of mast cells to clarify the role of these cells in
      gastric mucosal inflammation induced by H. pylori. Mast cells prepared from rat
      abdominal cavity were incubated with H. pylori for 30 min. The protein
      concentrations of H. pylori water extract used in this study were 0.5-3 mg/ml.
      The degranulation of mast cells were monitored morphologically by phase contrast
      microscopy equipped with time-lapse video recording system and biochemically by
      measuring histamine and beta-hexosaminidase. H. pylori water extract induced the
      degranulation of mast cells dose-dependently. The identical experiment was
      performed without extracellular calcium, and no significant degranulation was
      found. The data indicates that the degranulation of mast cells by H. pylori water
      extract depend on extracellular calcium. The present results indicate that H.
      pylori might be involved in the gastric mucosal inflammation as a trigger of mast
      cell degranulation for releasing chemical mediators.

PMID- 10210152
TI  - Nitric oxide, superoxide radicals and mast cells in pathogenesis of indomethacin
      induced small intestinal lesions in rats.
AB  - We investigated the pathogenic mechanism of indomethacin-induced small intestinal
      lesions, in relation to nitric oxide (NO), superoxide radicals and mast cells.
      Rats received indomethacin (1-6 mg/kg) s.c. once daily for 3 days, and the small
      intestine was examined for lesions 24 hr after the final administration of
      indomethacin. Indomethacin caused hemorrhagic lesions in the small intestine,
      mostly in the jejunum and ileum, in dose- and time-dependent manners, with
      concomitant increase of mucosal microvascular permeability. This treatment also
      caused an increase of inducible NO synthase (iNOS) activity with the expression
      of its mRNA, myeloperoxidase (MPO) activity as well as thiobarbituric acid
      reactants (TRBAS) in the mucosa, and the changes in iNOS activity preceded those
      in MPO activity and TRBAS as well as lesion development. These lesions induced by
      indomethacin were prevented by aminoguanidine (a selective inhibitor of iNOS),
      dexamethasone (an inhibitor of iNOS mRNA transcription), allopurinol (a xanthine
      oxidase inhibitor), hydroxyurea (a neutrophil reducing agent) and FR167653 (an
      inhibitor of interleukin-1/tumor necrosis factor-alpha production) as well as
      16,16-dimethyl prostaglandin E2n. Likewise, the severity of these lesions was
      also reduced by mast cell stabilizers FPL-52694 and disodium cromoglycate and a
      lipoxygenase inhibitor TMK-688, but not affected by tripelennamine (a histamine
      H1-receptor antagonist) or methysergide (a serotonin receptor antagonist). These
      results suggest that: 1) the pathogenic mechanism of indomethacin-induced small
      intestinal lesions involves superoxide radicals as well as NO produced by iNOS,
      2) the deleterious effect of NO may be accounted for by the cytotoxic action of
      peroxynitrite, produced from NO in the presence of superoxide radicals, and 3)
      the mast cells may also be involved in the process of small intestinal
      ulceration, although the mediator responsible remains undefined.

PMID- 10210153
TI  - Gastroprotection and control of food intake by leptin. Comparison with
      cholecystokinin and prostaglandins.
AB  - Circulating peptide leptin which is the product of the ob gene is known to
      provide feedback information on the size of fat stores to central OB-receptors
      that control food intake. Recently, leptin messenger RNA and leptin protein have
      been detected in gastric epithelium and leptin was found to be released by CCK
      into circulation but the physiological role of this gastric leptin remains
      unknown. As CCK has been reported to protect gastric mucosa against various
      noxious agents, we designed the study to determine the influence of leptin and
      CCK on the gastroprotection and the control of food intake and to compare them
      with classic gastroprotective substance, prostaglandin E2, in rats with acute
      gastric mucosal lesions induced by topical application of 75% ethanol. Four
      series of Wistar rats (A, B, C and D) were used to determine; A) the effects of
      various doses of leptin (0.1-10 microg/kg) given intraperitoneally (i.p.) on
      ethanol-induced gastric lesions, gastric blood flow (GBF) and plasma levels of
      immunoreactive leptin; B) the effects of various doses of CCK-8 (0.1-10 microg/kg
      i.p.) on ethanol-induced gastric lesions, GBF and plasma levels of leptin; C) the
      effects of various doses of PGE2 (12.5--100 microg/kg) given intragastrically
      (i.g.) on ethanol-induced gastric lesions and GBF and D) the influence of leptin,
      CCK and PGE2 on the intake of liquid meal in rats. Rats were anesthetized with
      ether 1 h after i.g. administration of 75% ethanol to measure the GBF using H2
      gas clearance technique and blood samples were withdrawn for the measurement of
      plasma leptin levels by radioimmunoassay (RIA). Food intake was assessed in
      separate group of rats fasted 18 h and then fed with liquid caloric meal. Leptin,
      CCK and PGE2 reduced dose-dependently gastric lesions induced by 75% ethanol, the
      dose reducing these lesions by 50% (ED50) being, respectively, 1 microg/kg, 5
      microg/kg and 20 microg/kg. The protective effects of leptin, CCK-8 and PGE2 were
      accompanied by significant attenuation of the fall of the GBF caused by ethanol.
      Leptin and CCK reduced also dose-dependently the food intake while PGE2 was not
      effective. Leptin and CCK resulted a dose-dependent increment in the plasma
      leptin levels. We conclude that: 1) exogenous leptin and CCK, causing similar
      increments in plasma immunoreactive leptin levels, protect dose-dependently
      gastric mucosa against the damage provoked by 75% ethanol; 2) Leptin and CCK
      afford similar gastroprotective activity to that attained with PGE2 but unlike
      PGE2 were highly effective in the reduction in food intake and 3) the protective
      effects of leptin, CCK and PGE2 were accompanied by significant increase of GBF
      suggesting that the protection afforded by these substances are mediated, at
      least in part, by gastric hyperemia.

PMID- 10210154
TI  - Calcitonin gene-related peptide can attenuate or augment pancreatic damage in
      caerulein-induced pancreatitis in rats.
AB  - We have recently shown that treatment with calcitonin gene-related peptide (CGRP)
      before and during induction of acute pancreatitis exhibits a protective effect
      against pancreatic damage evoked by overdose of caerulein. Studies in the stomach
      have shown that administration of CGRP exhibits dual action on gastric mucosa,
      CGRP administration before induction of gastric lesions, protects gastric mucosa
      against damage, whereas treatment with this peptide after development of gastric
      ulcer exacerbates mucosal injury. These observations prompt us to determine the
      influence of CGRP administrated before and after induction of pancreatitis on
      development and evolution of pancreatic tissue damage. METHODS: Acute
      pancreatitis was induced by s.c. infusion of caerulein (10 microg/kg/h) for 5 h.
      CGRP was administrated (10 microg/kg s.c. per dose) 30 min prior to caerulein
      infusion and 3 h later during caerulein infusion or at the time 1 h, 4 h and 7 h
      after the end of caerulein infusion. Rats were sacrificed at the time 0 h, 3 h or
      9 h after cessation of caerulein administration. The pancreatic blood flow (PBF),
      plasma activity of amylase, plasma interleukin-1beta concentration, cell
      proliferation, biochemical and morphological signs of pancreatitis were examined.
      RESULTS: Caerulein-induced pancreatitis (CIP) led to 42% decrease in DNA
      synthesis, 30% inhibition of PBF, as well as, a significant increase in
      pancreatic weight, plasma amylase activity, plasma interleukin-1beta
      concentration, and development of the histological signs of pancreatic damage
      (edema, leukocyte infiltration and vacuolization). Treatment with CGRP prior and
      during induction of CIP attenuated the pancreatic damage what was manifested by
      partial reversion of the drop in DNA synthesis (40.9+1.7 v. 34.2+2.0 dpm/microg
      DNA) and PBF (83+3% v. 70+3%). Increases in pancreatic weight and plasma
      interleukin-1beta were reduced. Morphology showed improvement of pancreatic
      integrity. Administration of CGRP after induction of CIP aggravated pancreatic
      damage what was manifested by additional decrease in PBF and DNA synthesis. Also
      pancreatic weight as well as histological signs of pancreatic damage were
      increased. CONCLUSIONS: (1) Administration of CGRP before and during induction of
      pancreatitis protects pancreas against pancreatic damage. (2) Treatment with CGRP
      after development of CIP aggravates pancreatic damage.

PMID- 10210155
TI  - Interaction between L-arginine: no system and cyclooxygenase metabolic products
      of arachidonic acid in coronary autoregulation.
AB  - Coronary autoregulation (CA) is the intrinsic ability of the heart to maintain
      its nutritive blood supply constant over a wide range of perfusion pressure. This
      phenomenon is regulated through several control mechanisms, while metabolic and
      myogenic control mechanism have dominant effects. In last few years, endothelial
      control mechanism, which is part of metabolic control, was intensive
      investigated. Dominant topic of endothelial-investigation was bioregulatory L
      arginine: NO system, with his effective product--nitric oxide (NO). On the other
      hand, cyclooxygenase metabolic pathway products of arachidonic acid plays an
      important role in the control of vasomotor tone of coronary arteries. For this
      purpose, the aim of our study was to evaluate role of L-arginine: NO system,
      cyclooxygenase metabolites of arachidonic acid, as well as, their interactions in
      the control of CA of the isolated rat heart.. In our study rat hearts
      autoregulate CF between 50 and 90 cm H2O of CPP. Basal release (at 60 cm H2O) of
      NO (as nitrite), cAMP, cGMP and HX+X (i.e. adenosine) amounted to 2.85+/-0.25
      nmol/min/g wt, 29.45+/-2.22 pmol/min/g wt, 0.43+/-0.08 pmol/min/g wt and 37.50+/
      2.89 nmol/min/g wt respectively. Release of NO, cAMP and cGMP were strictly
      parallel with CPP-CF curve, while release of adenosine (i.e. HX + X) was an
      inverse function of perfusion pressure. Inhibition of NOS (L-NAME, 30 micromol/l)
      significantly widened autoregulatory range (40-100 cm H2O), with significant
      reduction in CF and NO- and cGMP release, while release of cAMP was completely
      reversed in the presence of L-NAME. However, inhibition of cyclooxygenase didn't
      influence autoregulatory range, with similar changes of NO- and cAMP-release and
      completely inversed values of released adenosine. When L-NAME an indomethacin (an
      nonspecific COX-inhibitor), 3 micromol/l where added together, they exhibit
      interactions between these two enzymatic systems. Namely, when L-NAME was added
      first, indomethacin didn't influence hemodynamic effects of NOS-inhibitor. On the
      other hand, when COX-inhibitor was added first, L-NAME widened autoregulatory
      range in small manner as after control autoregulatory experiments (40-90 cm H2O).
      All hemodynamic changes were followed with similar changes in NO-release, what
      suggest that exist interaction between L-arginine: NO system and COX-metabolites
      in the regulation of coronary autoregulation.

PMID- 10210156
TI  - Effects of nitroglycerin on energy metabolism of rat reticulocytes.
AB  - Nitric oxide (NO) in many cells inactivates aconitase and mitochondrial
      respiratory chain, and influenced glyceraldehyde 3-phosphate dehydrogenase
      activity. The aim of this study was to evaluate role of nitroglycerin (NTG), a
      widely used NO donor, on energy metabolism of rat reticulocytes. Rat reticulocyte
      rich red blood cell suspensions containing 70-100% of reticulocytes, were
      aerobically incubated without (control) or in the presence of different
      concentrations of (a) NTG (0.1, 0.25, 0.5, 1.0, 1.5 mmol/l), (b) 8-Br-cGMP (0.1,
      0.5, 1.0 mmol/l) and (c) NaNO2 and NaNO3 (1 mmol/l). NTG in dose- and time
      dependent manner decreased total (p>0.05; EC50 = 0.78+/-0.05 mmol/l) and coupled
      (p<0.05; EC50 = 0.50+/-0.04 mmol/l) and increased uncoupled oxygen consumption
      (p<0.05: EC50 = 0.36+/-0.01 mmol/l). They were accompanied by stimulation of
      glycolysis, as measured by increased glucose consumption and lactate accumulation
      (p<0.001 EC50 = 0.53 and 0.53 mmol/l, respectively). Levels of all glycolytic
      intermediates in the presence of NTG indicate stimulation of HK-PFK, GA3PDH and
      PK activity. NTG significantly decreased ATP level, which accompanied by
      increased ADP and AMP levels. However, level of total adenine nucleotides (TAN)
      was significantly lower, which was consequence of increased catabolism of adenine
      nucleotides (increased hypoxanthine level; p<0.05). Stimulation of glycolysis
      accompanied with inhibition of the OxP, activation of HK-PFK, decrease of ATP and
      simultaneous rise of ADP and AMP levels, all together represent an example of
      Pasteur effect occurring in NTG-treated reticulocytes. In rat reticulocytes under
      steady state conditions 93% of overall energy was produced by OxP, but only 7% by
      glycolysis. Due to decrease of coupled oxygen consumption in the presence of NTG,
      ATP production via OxP was significantly diminished. Simultaneous increase of
      glycolytic ATP production is not enough to provide constant either ATP production
      or concentration. Calculated mean ATP-turnover time was prolonged even for 45% in
      the presence of 1.5 mmol/l NTG. Metabolic effects of NTG were not mimic by
      exogenous 8-Br-cGMP, NaNO2 or NaNO3, which indicate that NTG induced a)
      inhibition of coupled respiration and b) stimulation of glycolysis in rat
      reticulocytes are mediated by NO as an effector molecule.

PMID- 10210157
TI  - The effect of nitrendipine on renal haemodynamics and tubular reabsorption and
      its neural control in anaesthetised rats with chronic renal failure.
AB  - This study examined the influence of a calcium channel antagonist, nitrendipine,
      on blood pressure and kidney function in a rat model of chronic renal failure.
      Additionally, the effects of low frequency renal nerve stimulation were studied
      in the presence and absence of nitrendipine. Male Wistar rats were fed a diet
      high in adenine for 4 weeks and then acutely anaesthetised and prepared for renal
      functional measurements. Blood pressure was elevated but renal blood flow and
      glomerular filtration rate were reduced, between 30 to 50%, urine flow and
      absolute sodium excretion were lower and fractional sodium excretion was two to
      three times higher than in normal rats. Nitrendipine (0.25 microg/kg/min i.v.)
      decreased blood pressure at 114+/-7 mm Hg, by 11% (P<0.05), increased left renal
      blood flow, at 1.3+/-0.2 ml/min(-1) g(-1), by 16% (P<0.01), and urine flow,
      absolute and fractional sodium excretions, by between 50-83% (all P<0.05). Renal
      nerves stimulation (0.7-1.3 Hz, 15V, 0.2 ms) decreased (P<0.02) left renal blood
      flow by 10% but had no effect on excretory variables, irrespective of
      nitrendipine administration. These results show that in renal failure rats the
      vascular and tubular responses to nitrendipine are preserved. However, the neural
      regulation of tubular reabsorption is abolished in this experimental model,
      irrespective of nitrendipine administration.

PMID- 10210158
TI  - Antithrombotic activity of losartan in two kidney, one clip hypertensive rats. A
      study on the mechanism of action.
AB  - The potential antithrombotic action of losartan, an AT1 receptor antagonist,
      administered to two-kidney, one-clip rats (2K1C) in an experimental model of
      venous thrombosis was evaluated. The involvement of nitric oxide (NO) in this
      effect was also studied. Venous stasis was induced by ligation of the vena cava.
      Losartan after single dose (10 mg/kg, p.o.) significantly reduced the venous
      thrombus growth. The antithrombotic action of losartan in 2K1C rats was abolished
      by N(G)-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg s.c.) and restored by L
      arginine (1000 mg/kg s.c.). Platelet adhesion to fibrillar collagen significantly
      decreased after administration of losartan. No changes in primary hemostasis and
      platelet aggregation were observed. Moreover, coagulation parameters such as
      activated partial thromboplastin time, prothrombin time and euglobulin clot lysis
      time were found unchanged after losartan administration either in systemic
      circulation or at the place of thrombus formation. Our results indicate that
      antithrombotic activity of losartan in 2K1C rats is NO--dependent; observed
      inhibition of platelet adhesion could also play a role in this phenomenon.

PMID- 10210159
TI  - Experimental studies on the anticoagulant and antithrombotic effects of sodium
      and calcium pentosan polysulphate.
AB  - In the present study we have compared the antithrombotic and anticoagulant
      properties of sodium and calcium derivatives of pentosan polysulphate (Na-PPS, Ca
      PPS). The antithrombotic effect of these agents have been investigated in an
      experimental thrombosis model in which rat mesenteric venules diameter of 20-30
      microm were injured by well defined Argon laser lesions. Furthermore, the in vivo
      and in vitro anticoagulant activities (aPTT, Heptest) of these agents have been
      studied. Thrombus formation was significantly inhibited after s.c. injection of
      Na-PPS and Ca-PPS in doses above 10 mg/kg. The duration of the antithrombotic
      effect lasted 8 h for Na-PPS and 12 h for Ca-PPS. After oral administration of Na
      PPS an antithrombotic effect was not observed. Oral application of Ca-PPS in
      doses higher than 20 mg/kg significantly inhibited thrombus formation. Na-PPS and
      Ca-PPS markedly prolonged clotting time in aPTT and Heptest in concentrations
      ranging from 0.01 to 0.2 mg/ml rat PTT. Two h after s.c. administration of these
      agents in a dose 10 mg/kg, the aPTT increased 3-fold and Heptest 2.5-fold
      compared to controls. After oral application of 50 mg/kg Na-PPS and Ca-PPS no
      effect on coagulation test could be measured.

PMID- 10210160
TI  - The pineal and oxytocin synthesis.
AB  - The aim of this study was to investigate the effect of pineal removal on oxytocin
      synthesis in the hypothalamus using the colchicine method. To this end, rats were
      injected intracerebroventricularly (i.c.v.) with colchicine solution (5 microg/5
      microl) or normal saline and decapitated 20 h later. The animals were either
      pinealectomized or sham-operated two or eight weeks before i.c.v. injection. The
      oxytocin content in the hypothalamus was significantly higher in colchicine
      treated rats whereas no significant differences were seen in the neurohypophysial
      hormone level between saline- or colchicine-injected animals. Thus, colchicine
      inhibited the hormonal transport but probably did not affect the function of the
      neurohypophysis. Two weeks after pinealectomy neither the oxytocin synthesis rate
      nor its neurohypophysial content were significantly different from control
      values. The oxytocin synthesis rate was increased markedly eight weeks after
      pineal removal. At that time, the neurohypophysial oxytocin content was reduced
      suggesting the increased secretion of the hormone. It is concluded that the
      pineal has an inhibitory impact on both oxytocin synthesis and release.

PMID- 10210161
TI  - Enhanced proliferation and progesterone production by porcine granulosa cells
      cultured with pseudorabies virus growth factor (PRGF).
AB  - The objective of this research was to study possible interactions of pseudorabies
      virus growth factor (PRGF) with ovarian tissue. Granulosa cells isolated from
      porcine ovaries were cultured as monolayers for 6 days in a control medium
      without PRGF and in medium supplemented with different doses of this agent.
      Increased population density and change towards more fibroblastic-like shape of
      cells cultured with 10(9) I.U PRGF was observed when compared with control
      culture. The cells divided significantly faster during 6 days of culture under
      the influence of 10(3), 10(4), 10(5), 10(6), 10(7), 10(8) and 10(9) I.U./ml of
      PRGF at a dose dependent manner. PRGF in a dose 10(9) I.U. added to cultured
      cells isolated from small and medium follicles did not influence progesterone
      secretion . An increase of progesterone secretion under the influence of PRGF in
      all investigated days of cultures was observed in cells isolated from large
      preovulatory follicles. The marked increase in progesterone content in PRGF
      treated culture in doses of 0.5x10(7), 0.5x10(8), 0.5x10(9) I.U. was observed
      during 4 and 6 days of culture. The rise of progesterone content was not
      connected with increased number of secretory cells, but with a stimulation of
      production per cell. PRGF exerted no visible effect on progesterone secretion by
      granulosa cells from small and medium follicles cultured for 6 days. The
      presented in vitro data provide evidence for a local action of PRGF in the
      follicle depending on the stage of follicular development and duration of
      exposure. Precise relevance of the interaction of PRGF with follicular
      development requires further study.

PMID- 10210163
TI  - Effects of alcohol on the synthesis and expression of hypothalamic peptides.
AB  - Studies aimed at analyzing the deleterious effects of excess alcohol in the brain
      have revealed structural alterations that are often associated with functional
      and behavioral disturbances. Among the neuronal damage related to prolonged
      alcohol exposure, alterations in the synthesizing capabilities and levels of
      expression of neuroactive peptides have been increasingly reported. Actually,
      such changes frequently represent the sole repercussion of acute and short-term
      exposure to ethanol. This review gathers the existing data on the effects of
      ethanol exposure on the synthesis and expression of hypothalamic peptides. Amid
      those that can act both as neurotransmitters and neurohormones, we allude to
      vasopressin, corticotropin-releasing hormone, thyrotropin-releasing hormone and
      pro-opiomelanocortin and related peptides produced by paraventricular, supraoptic
      and arcuate neurons. With respect to peptides that act exclusively as
      neurotransmitters, we address the effects of alcohol on vasoactive intestinal
      polypeptide, gastrin-releasing peptide, somatostatin and vasopressin synthesized
      by suprachiasmatic neurons. Hypothalamic neurons that produce peptides that act
      as neurotransmitters are supposed to be modulated primarily by influences exerted
      by neuronal afferents, whereas those producing peptides that additionally act as
      neurohormones are also regulated by peripheral stimuli (e.g., plasma levels of
      circulating hormones, osmotic challenges). These peculiar features endue the
      hypothalamus with characteristics that are particularly propitious to enlighten
      the still cryptic mechanisms underlying the ethanol effects on protein synthesis.

PMID- 10210162
TI  - A partial agonist at strychnine-insensitive glycine sites facilitates spatial
      learning in aged rats.
AB  - 1-Aminocyclopropanecarboxylic acid (ACPC) is a high affinity ligand at strychnine
      insensitive glycine sites of the N-methyl-D-aspartate (NMDA) channels and
      exhibits partial agonist properties in both biochemical and electrophysiological
      measures. While ACPC was reported active in animal models used to evaluate
      potential antidepressants and anxiolytics, its effects on learning and memory are
      unknown. In the present study we investigated the effects of ACPC on spatial
      learning in the Morris water maze. On a schedule of 12 learning trials, one trial
      per day, mature male Wistar rats (3 months of age) rapidly acquired the task.
      Electroconvulsive shocks applied after each of the learning trials markedly
      inhibited the consolidation of spatial memory. Administration of either a
      muscarinic agonist, arecoline (1 mg/kg) or ACPC (250 or 400 mg/kg) 20 min before
      each of the learning trials did not affect the acquisition of spatial learning.
      Aged (16 months old) male Wistar rats demonstrated difficulties in the
      acquisition of spatial learning task. In these subjects, ACPC administered 20 min
      before each of the learning trials at a dose of 400, but not 250 mg/kg,
      facilitated the acquisition of spatial memory as indicated on trials 3-5. ACPC
      did not affect the strength of spatial memory as assessed at the end of
      conditioning, by measuring swimming behavior of rats in the pool with platform
      removed. It is suggested that ACPC may alleviate learning deficits observed in
      the elderly.

PMID- 10210164
TI  - Borna disease virus-induced hippocampal dentate gyrus damage is associated with
      spatial learning and memory deficits.
AB  - In neonatally inoculated rats, Borna disease virus (BDV) leads to a persistent
      infection of the brain in the absence of an inflammatory response and is
      associated with neuroanatomic, developmental, physiologic, and behavioral
      abnormalities. One of the most dramatic sites of BDV-associated damage in the
      neonatal rat brain is the dentate gyrus, a neuroanatomic region believed to play
      a major role in spatial learning and memory. The absence of a generalized
      inflammatory response to neonatal BDV infection permits direct effects of viral
      damage to the dentate gyrus to be examined. In this report, neonatally BDV
      infected rats at various stages of dentate gyrus degeneration were evaluated in
      the Morris water maze, a swimming test that assesses the rats' capacity to
      navigate by visual cues. Our data demonstrate progressive spatial learning and
      memory deficits in BDV-infected rats that coincided with a gradual decline in the
      estimated hippocampal dentate gyrus neuron density.

PMID- 10210165
TI  - Regional distribution and control of tyrosine hydroxylase activity in the quail
      brain.
AB  - Tyrosine hydroxylase (TH) activity, the rate-limiting step in the synthesis of
      catecholamines, was quantified in the preoptic area-hypothalamus of adult male
      Japanese quail by a new assay measuring the tritiated water production from 3,5
      [3H]-L-tyrosine. Maximal levels of activity were observed at a 20-25 microM
      concentration of substrate, with more than 50% inhibition of the activity being
      recorded at a 100 microM concentration. TH activity was linear as a function of
      the incubation time during the first 20 min and maximal at a pH of 6.0. TH was
      heterogeneously distributed in the quail brain with highest levels of activity
      being found (in decreasing order) in the mesencephalon, diencephalon, and
      telencephalon. Given the large size of the telencephalon, this is the brain area
      that contains, as a whole, the highest level of enzyme activity. TH inhibitors
      that have been well-characterized in mammals, such as 3-iodo-L-tyrosine and L
      alpha-methyl-p-tyrosine (AMPT) completely inhibited the enzyme activity at a 100
      microM concentration. In mammals, the accumulation of catecholamines exerts a
      negative feedback control on TH activity. Similar controls were observed in the
      quail brain. Two inhibitors of the DOPA decarboxylase that should lead to
      accumulation of DOPA depressed TH activity by 60% or more, and the inhibitor of
      the dopamine beta-hydroxylase, fusaric acid that should cause an accumulation of
      dopamine, suppressed 90% of the TH activity. The addition of exogenous DOPA,
      dopamine, or norepinephrine to the brain homogenates also strongly inhibited TH
      activity, independently confirming the feedback effects of the enzyme products on
      the enzyme activity. These data demonstrate that TH activity in the quail brain
      is heterogeneously distributed and acutely regulated, as it is in mammals, by the
      accumulation of its products and of the derived catecholamines.

PMID- 10210166
TI  - Changes in NADPH-diaphorase positivity induced by status epilepticus in
      allocortical structures of the immature rat brain.
AB  - The distribution and time course of changes of nicotinamide adenine dinucleotide
      phosphate diaphorase (NADPH-d) positivity were studied in immature rats (12 and
      25 days old) surviving motor status epilepticus (SE) induced by a high dose of
      pilocarpine. Motor SE characterized by continuous convulsions was interrupted
      after 2 h by an injection of clonazepam (0.5 mg/kg or 1 mg/kg in 12- and 25-day
      old rats, respectively) in order to reduce mortality. Correlation between
      electroencephalographic and behavioral seizure activity was confirmed using
      animals with electrodes implanted bilaterally in the hippocampus and sensorimotor
      cortex. Brains were examined 2, 6, 13, and 21 days after motor SE using NADPH
      diaphorase histochemistry. Two types of changes were found in both age groups:
      (a) decrease of NADPH-d positivity occurred in both neuropil and cell bodies in
      piriform, periamygdalar, and entorhinal cortices; and (b) NADPH-d positivity was
      induced in the cell bodies in the hippocampal fields CA1/2, CA3, and dentate
      gyrus. These changes were more intense in animals surviving SE at postnatal day
      25 than in younger age group, and they peaked 2 days after SE. The changes
      observed after SE disappeared quickly in 12-day-old rat pups, where only moderate
      changes could be observed in piriform, periamygdalar, and entorhinal cortices 6
      days after SE, whereas the changes in the histochemical positivity persisted in
      older animals even 21 days after SE.

PMID- 10210167
TI  - Modulation of 5-hydroxytryptamine release in hippocampal slices of rats: effects
      of fimbria-fornix lesions on 5-HT1B-autoreceptor and alpha2-heteroreceptor
      function.
AB  - Fimbria-fornix lesions disrupt important parts of serotonergic and noradrenergic
      hippocampal afferents and elicit sprouting of sympathetic fibers from the
      superior cervical ganglion. Since 5-hydroxytryptamine (5-HT) release in the
      hippocampus is modulated by 5-HT1B auto- and alpha2-heteroreceptors, we
      investigated whether such lesions may alter these presynaptic mechanisms.
      Hippocampal slices of sham-operated (SHAM) and fimbria-fornix-lesioned (LES) rats
      (14 months after surgery) were preincubated with [3H]5-HT, superfused
      continuously, and stimulated electrically using two stimulation conditions:
      either (a) 360 pulses 3 Hz, or (b) 20 pulses 100 Hz (2 ms, 28 mA, 4 V/chamber).
      The amount of [3H]5-HT taken up by slices from LES rats was significantly
      reduced, whereas the evoked 5-HT release (in percent of tissue-3H) was unchanged
      compared to that of SHAM rats. The 5-HT1B agonist CP 93,129 or the alpha2-agonist
      UK 14,304 reduced the evoked 5-HT release more potently in slices from LES rats,
      but only using stimulation condition (a), which permits inhibition by
      endogenously released transmitters. In LES rats, the facilitatory effect of the 5
      HT antagonist metitepine was weaker, whereas that of the alpha2-antagonist
      idazoxane was more pronounced than in SHAM rats. In LES rats, hippocampal 5-HT
      content was reduced to about 45% of SHAM levels, whereas that of noradrenaline
      was increased by about 30% (high-performance liquid chromatography). We conclude:
      (1) despite LES-induced changes in tissue levels of endogenous ligands, there is
      no down- or upregulation of 5-HT1B-autoreceptors or alpha2-heteroreceptors on
      serotonergic neurons in the denervated rat hippocampus. (2) The reduced
      endogenous autoinhibition (by 5-HT) seems to be compensated for by an increased
      heteroinhibition (by noradrenaline).

PMID- 10210168
TI  - Dexamethasone effects on cerebral protein synthesis prior to and following
      hypoxia-ischemia in immature rat.
AB  - We hypothesized that the neuroprotection against cerebral hypoxic-ischemic damage
      observed with dexamethasone treatment in immature rats is related to a change in
      cerebral protein synthesis. Six-day-old Wistar rats were injected with either
      vehicle (10 ml/kg) or dexamethasone (0.1 mg/kg) 24 h prior to cerebral hypoxia
      ischemia. Local cerebral protein synthesis (incorporation of 14C-leucine into
      proteins) was measured in 7-day-old rats during normoxia, during hypoxia
      ischemia, and after hypoxia-ischemia which was produced with right carotid artery
      ligation and 2-h exposure to 8% O2. In normoxic controls, cerebral protein
      synthesis was similar in dexamethasone and vehicle-treated animals. During
      hypoxia-ischemia, local cerebral protein synthesis decreased markedly (p <
      0.0001) in ischemic regions ipsilateral to the occlusion, irrespective of
      treatment. After hypoxia-ischemia, protein synthesis declined even further in
      vehicle-treated animals. Reductions in protein synthesis were substantially more
      severe in vehicle- than dexamethasone-treated animals, particularly after hypoxia
      ischemia (p < 0.0001). Thus, neuroprotection with dexamethasone is not related to
      a reduction in basal levels of cerebral protein synthesis, but is associated with
      an improved protein synthesis during and following hypoxia-ischemia.

PMID- 10210169
TI  - Nucleus basalis injections of N-methyl-D-aspartate enhance memory of rats in the
      double Y-maze.
AB  - N-methyl-D-aspartate (NMDA) receptors have been implicated in learning and
      memory. Many findings show that NMDA receptor antagonists impair memory. Few
      studies, however, have investigated the role of NMDA receptor agonists in
      mnemonic function. The present study examined the effects of nucleus basalis
      magnocellularis (nbm) injections of NMDA on memory. Rats were trained in a two
      component double Y-maze task consisting of a spatial discrimination and a delayed
      alternation. Rats (n = 7) were surgically implanted with bilateral cannulae in
      the nbm prior to maze training. Once trained, animals received bilateral nbm
      injections (0.5 microl) of saline (0.9%), NMDA (50, 75, and 100 ng/side), and the
      benzodiazepine receptor partial inverse agonist N-methyl-beta-carboline-3
      carboxamide (FG 7142; 200 ng/side), in a counterbalanced order. During testing,
      delays (0, 30, 60 s) were introduced. Nbm FG 7142 or NMDA (50 ng/side) produced
      an improvement in the delayed alternation task. Results support the hypothesis
      that nbm NMDA receptors are involved in cognitive processes mediating memory.

PMID- 10210170
TI  - Calcium currents of embryonic and adult neurons in serum-free culture.
AB  - Calcium channels affect many neuronal functions, including membrane electrical
      excitability, synaptic transmission, cellular homeostasis, gene transcription,
      growth, and development. We used recently developed methods for serum-free
      culture of adult and embryonic rat neurons to study the development of voltage
      sensitive calcium currents. We compared characteristics of voltage-sensitive
      calcium currents in neurons taken from juvenile adult (2-4 months of age) and
      embryonic (day 18) rats. Mean total calcium currents were 67% larger in embryonic
      compared to adult neurons. At both ages, calcium currents contained only high
      voltage-activated components, and lacked low-voltage-activated components. High
      voltage-activated currents were significantly greater in embryonic than in adult
      neurons, but the voltage-sensitivity was similar. Our adult cultures, but not
      embryonic cultures, contain basic fibroblast growth factor (FGF2), which enhances
      survival. We tested the effect of FGF2 and found that growth in its presence
      caused increased calcium currents in both embryonic and adult neurons. We
      conclude that in neurons cultured in serum-free medium, neuronal development from
      embryonic to juvenile adult ages is associated with a significant reduction in
      voltage-sensitive calcium currents.

PMID- 10210171
TI  - Tenascin-C expression in the trunk of wild-type, cyclops and floating head
      zebrafish embryos.
AB  - The function and the regulation of the expression of the extracellular matrix
      molecule tenascin-C during embryonic development are still unclear. In the
      present study, the expression of tenascin-C was analyzed in the trunk of
      zebrafish at the end of the first embryonic day. An antiserum raised against a
      zebrafish tenascin-C (TN-C) fusion protein reacted with 220 (doublet), 200, and
      160 KD peptides. In situ hybridization showed that in the zebrafish wild-type
      embryo, tn-c mRNA was expressed by somites, neural crest cells, roof plate,
      notochord, hypochord, and tail fin bud. Thus, the expression of tn-c mRNA is an
      excellent marker for the differentiation of most zebrafish trunk structures.
      Immunolabelling with the anti-TN-C antibody was detected in the migratory pathway
      of neural crest cells and in the intersomitic furrows. In situ hybridization
      analysis of the zebrafish cyclops mutants, lacking the midline floor plate cells,
      showed normal expression of tn-c mRNA in all trunk structures. Analysis of the
      floating-head mutant, lacking the notochord, showed that tn-c mRNA expression in
      neural crest cells, roof plate, and tail fin bud is normal, but it is defective
      in the somites. By showing that the notochord, but not the floor plate, cells are
      required for normal tn-c expression in the trunk, this work provides new
      information on the role played by the embryonic axial structures in the
      regulation of the expression of tn-c during the development of zebrafish and
      allows new conclusions about somite patterning in the cyclops and floating-head
      zebrafish mutants.

PMID- 10210172
TI  - Rapid expression of polymorphic ovine prion proteins and studies on their
      protease sensitivity.
AB  - We have used coupled and uncoupled in vitro transcription/translation to express
      rapidly aglycosyl ovine prion proteins from ovine genomic DNA genotyped for
      scrapie susceptible and nonsusceptible polymorphisms. Unlike previous in vitro
      studies of prion proteins, this method does not require cloning or laborious
      extractions. To our knowledge, this is the first report of ovine PrP expression
      at low (ng) levels under the control of an Escherichia coli promoter and ribosome
      binding site both coded for in the polymerase chain reaction primer. The rapidity
      of this approach could form the basis of a high throughput screening assay for
      PrP interactions, as proteins were expressed in a matter of hours from genomic
      DNA as the starting material. There was no difference observed in proteinase K
      sensitivity between prion translation products containing either scrapie
      susceptible or nonsusceptible polymorphisms.

PMID- 10210173
TI  - Gonadotrophin-releasing hormone and oxytocin secretion from the hypothalamus in
      vitro during pro-oestrus: the effects of time of day and melatonin.
AB  - An accurately timed surge of luteinizing hormone (LH), during the second half of
      the day of pro-oestrus in rats, is a crucial part of the endocrine signal that
      leads to expulsion of an ovum from an ovarian follicle. LH release is partly
      controlled by a number of peptides, including gonadotrophin-releasing hormone
      (GnRH) and oxytocin, which travel from the hypothalamus to the pituitary. The
      profile of secretion of these peptides is poorly understood. Therefore, the
      amounts of GnRH and oxytocin that were secreted from hypothalamic explants were
      determined at several time points during the day of pro-oestrus. Basal secretion
      of oxytocin from hypothalami taken later in pro-oestrus was greater than from
      hypothalami taken earlier in the day (p < 0.02). On the other hand, basal
      secretion of GnRH decreased during the day of pro-oestrus (p < 0.03). The
      different trends of GnRH and oxytocin secretion reveal that their secretion is
      regulated by distinct mechanisms. GnRH secretion was higher at midpro-oestrus
      than late in the day (o < 0.05) consistent with a peak of GnRH having been
      observed by others in portal blood in the second half of the day of pro-oestrus.
      Responsiveness of oxytocin to stimulation by K+ of the hypothalami declined from
      the early light hours to the evening dark hours (p < 0.02). Thus, oxytocin
      modulation might be achieved partly by modification of intracellular processes.
      Melatonin, secreted during hours of darkness, is frequently involved in
      modulating time-dependent events in mammals, but its contribution to peptide
      regulation during the ovulatory cycle is unclear. Melatonin was observed to
      inhibit basal oxytocin secretion from hypothalami collected during light hours (p
      < 0.05). The investigation has, therefore, revealed the potential for melatonin
      to modulate peptide secretion from the hypothalamus during the day of pro
      oestrus. We also observed that secretion from the hypothalamus of the two LH
      regulating peptides, GnRH and oxytocin, are differently regulated during the day
      of pro-oestrus.

PMID- 10210174
TI  - Autoradiography of [3H]glutamate binding during pentobarbital tolerance and
      withdrawal in the rat.
AB  - The influence of centrally administered pentobarbital on [3H]glutamate receptor
      binding in the rat brain was examined. Animals were rendered tolerant by
      intracerebroventricular (i.c.v.) infusion through osmotic minipumps with
      pentobarbital (300 microg/10 microl/h, for 6 days), and dependent, by 24 h after
      withdrawal from pentobarbital. Pentobarbital tolerant rats have significant
      increases in [3H]glutamate binding in the cortex and hippocampus area.
      Pentobarbital withdrawal produced increases in glutamate binding in many regions,
      e.g., the cortex, hippocampus area, thalamus, and cerebellum. These results show
      that chronic i.c.v. infusion with pentobarbital increases N-methyl-D-aspartate
      (NMDA) displaceable [3H]glutamate binding, suggesting that an increase in NMDA
      binding sites may play an important role in the development of tolerance to and
      withdrawal from pentobarbital.

PMID- 10210175
TI  - Single-unit activity of dorsomedial arcuate neurons and diurnal changes of
      tuberoinfundibular dopaminergic neuron activity in female rats with neonatal
      monosodium glutamate treatment.
AB  - Neonatal monosodium glutamate (MSG)-treated rats were used in this study to
      answer two questions: (1) whether or not the dopamine-responsive dorsomedial
      arcuate (dm-ARN) neurons are tuberoinfundibular dopaminergic (TIDA) neurons, and
      (2) whether or not the remaining TIDA neurons in MSG-treated rats are functioning
      normally. MSG (4 mg/g b. wt., subcutaneously [s.c.]) or saline was given to
      neonatal Sprague-Dawley rats on days 1, 3, 5, 7, and 9 after birth. The female
      rats were ovariectomized at 50 days of age and treated with estrogen for 1 week
      before they were used between 65-90 days of age. The tyrosine hydroxylase
      immunoreactive (TH-ir) neurons located in the dm and ventrolateral (vl) parts of
      the ARN were significantly reduced in MSG-treated rats, as determined by
      immunohistochemical method. Some TH-ir cells, however, were visible along the
      border of the third ventricle. Using single-unit recording in brain slices, we
      found that dopamine inhibited significantly fewer percentage of dm-ARN neurons in
      MSG-treated (28.2%, n = 39) than in saline-treated rats (73.3%, n = 15). In
      contrast, bombesin exhibited similar effects (over 70% excitation) in both
      groups. Using neurochemical means, neonatal MSG treatment produced significant
      decreases of both 3,4-dihydroxyphenylacetic acid and dopamine levels, but not
      their ratios, in the median eminence. Moreover, the diurnal change of TIDA
      neuronal activity persisted in the MSG-treated rats; so did the estrogen-induced
      afternoon prolactin surge. All these results indicate that neonatal MSG-treatment
      reduced the number and altered the location of TIDA and dopamine-responsive dm
      ARN neurons. The remaining TIDA neurons seemed to be able to maintain their basal
      activities and diurnal rhythm.

PMID- 10210177
TI  - Different effects of unilateral and bilateral hippocampal lesions in rats on the
      performance of radial maze and odor-paired associate tasks.
AB  - The hippocampus plays an important role in the declarative or explicit memory in
      humans and is necessary for allocentric spatial learning and olfactory memory in
      animals. In primates and rodents, the bilateral hemispheres of the brain
      (especially the forebrain) symmetrically and asymmetrically contribute to diverse
      cognitive manipulations. In this study, we investigated the role of the
      hippocampus in spatial memory and in odor-paired associate memory by unilaterally
      or bilaterally lesioning this region in rats. The bilateral removal, but not the
      unilateral removal, of the hippocampus impaired both the acquisition of spatial
      working memory in the radial maze task and the retrieval of maze performance
      tested 1 month after the acquisition trials. In contrast, neither bilateral nor
      unilateral removal impaired the odor-paired associate learning. These findings
      suggest that the hippocampus is critical to the spatial memory, and that a
      unilateral hippocampus is sufficient for executing a spatial task. The present
      results also indicate that the hippocampus plays a minor role in odor-dominated
      associate learning and that some kinds of memories in rats may be processed
      independently by the left or right hippocampus.

PMID- 10210176
TI  - Acute "binge" cocaine increases mu-opioid receptor mRNA levels in areas of the
      rat mesolimbic mesocortical dopamine system.
AB  - Autoradiography studies demonstrated that chronic "binge" cocaine administration
      increased mu-opioid receptor density in dopaminergically innervated rat brain
      regions, including the cingulate cortex, the nucleus accumbens, and the
      basolateral amygdala. The present study investigated the effects of a single day
      of binge-pattern cocaine administration (3 x 15 mg/kg, intraperitoneally [i.p.]
      at hourly intervals) on mu-opioid receptor mRNA levels in selected brain regions.
      Rats were sacrificed 30 min after the third injection and mRNA levels were
      measured by a quantitative solution hybridization RNase protection assay. Acute
      binge cocaine administration significantly increased mu-opioid receptor mRNA
      levels in the frontal cortex, nucleus accumbens, and amygdala, but not in the
      caudate-putamen, thalamus, hippocampus, and hypothalamus. As has been suggested
      for other G-protein coupled receptors, the rapid increase of MOR mRNA reported in
      this study might represent an adaptive response to compensate for a decrease in
      number of receptors following cocaine-induced opioid peptide release.

PMID- 10210178
TI  - The signal transducer gp130: solution structure of the carboxy-terminal domain of
      the cytokine receptor homology region.
AB  - The transmembrane glycoprotein gp130 is the common signal transducing receptor
      subunit of the interleukin-6-type cytokines. It is a member of the cytokine
      receptor superfamily predicted to consist of six domains in its extracellular
      part. The second and third domain constitute the cytokine-binding module defined
      by a set of four conserved cysteines and a WSXWS motif, respectively. The three
      dimensional structure of the carboxy-terminal domain of this region was
      determined by multidimensional NMR. The domain consists of seven beta-strands
      constituting a fibronectin type III-like topology. The structure reveals that the
      WSDWS motif of gp130 is part of an extended tryptophan/arginine zipper which
      modulates the conformation of the CD loop.

PMID- 10210180
TI  - Assignment of side-chain conformation using adiabatic energy mapping, free energy
      perturbation, and molecular dynamic simulations.
AB  - NMR spectroscopic analysis of the C-terminal Kunitz domain fragment (alpha3(VI))
      from the human alpha3-chain of type VI collagen has revealed that the side chain
      of Trp21 exists in two unequally populated conformations. The major conformation
      (M) is identical to the conformation observed in the X-ray crystallographic
      structure, while the minor conformation (m) cannot structurally be resolved in
      detail by NMR due to insufficient NOE data. In the present study, we have
      applied: (1) rigid and adiabatic mapping, (2) free energy simulations, and (3)
      molecular dynamic simulations to elucidate the structure of the m conformer and
      to provide a possible pathway of the Trp21 side chain between the two conformers.
      Adiabatic energy mapping of conformations of the Trp21 side chain obtained by
      energy minimization identified two energy minima: One corresponding to the
      conformation of Trp21 observed in the X-ray crystallographic structure and
      solution structure of alpha3(VI) (the M conformation) and the second
      corresponding to the m conformation predicted by NMR spectroscopy. A transition
      pathway between the M and m conformation is suggested. The free-energy difference
      between the two conformers obtained by the thermodynamic integration method is
      calculated to 1.77+/-0.7 kcal/mol in favor of the M form, which is in good
      agreement with NMR results. Structural and dynamic properties of the major and
      minor conformers of the alpha3(VI) molecule were investigated by molecular
      dynamic. Essential dynamics analysis of the two resulting 800 ps trajectories
      reveals that when going from the M to the m conformation only small, localized
      changes in the protein structure are induced. However, notable differences are
      observed in the mobility of the binding loop (residues Thr13-Ile18), which is
      more flexible in the m conformation than in the M conformation. This suggests
      that the reorientation of Trp2 might influence the inhibitory activity against
      trypsin, despite the relative large distance between the binding loop and Trp21.

PMID- 10210179
TI  - KM+, a mannose-binding lectin from Artocarpus integrifolia: amino acid sequence,
      predicted tertiary structure, carbohydrate recognition, and analysis of the beta
      prism fold.
AB  - The complete amino acid sequence of the lectin KM+ from Artocarpus integrifolia
      (jackfruit), which contains 149 residues/mol, is reported and compared to those
      of other members of the Moraceae family, particularly that of jacalin, also from
      jackfruit, with which it shares 52% sequence identity. KM+ presents an acetyl
      blocked N-terminus and is not posttranslationally modified by proteolytic
      cleavage as is the case for jacalin. Rather, it possesses a short, glycine-rich
      linker that unites the regions homologous to the alpha- and beta-chains of
      jacalin. The results of homology modeling implicate the linker sequence in
      sterically impeding rotation of the side chain of Asp141 within the binding site
      pocket. As a consequence, the aspartic acid is locked into a conformation
      adequate only for the recognition of equatorial hydroxyl groups on the C4
      epimeric center (alpha-D-mannose, alpha-D-glucose, and their derivatives). In
      contrast, the internal cleavage of the jacalin chain permits free rotation of the
      homologous aspartic acid, rendering it capable of accepting hydrogen bonds from
      both possible hydroxyl configurations on C4. We suggest that, together with
      direct recognition of epimeric hydroxyls and the steric exclusion of disfavored
      ligands, conformational restriction of the lectin should be considered to be a
      new mechanism by which selectivity may be built into carbohydrate binding sites.
      Jacalin and KM+ adopt the beta-prism fold already observed in two unrelated
      protein families. Despite presenting little or no sequence similarity, an
      analysis of the beta-prism reveals a canonical feature repeatedly present in all
      such structures, which is based on six largely hydrophobic residues within a beta
      hairpin containing two classic-type beta-bulges. We suggest the term beta-prism
      motif to describe this feature.

PMID- 10210182
TI  - Quench-flow experiments combined with mass spectrometry show apomyoglobin folds
      through and obligatory intermediate.
AB  - Folding of apomyoglobin is characterized by formation of a compact intermediate
      that contains substantial helicity. To determine whether this intermediate is
      obligatory or whether the protein can fold directly into the native state via an
      alternate parallel pathway, we have combined quench-flow hydrogen-exchange pulse
      labeling techniques with electrospray ionization mass spectrometry. The mass
      spectra of apomyoglobin obtained at various refolding times suggest that
      apomyoglobin indeed folds through a single pathway containing an obligatory
      intermediate with a significant hydrogen-bonded secondary structure content.

PMID- 10210181
TI  - A near-native state on the slow refolding pathway of hen lysozyme.
AB  - The refolding of four disulfide lysozyme (at pH 5.2, 20 degrees C) involves
      parallel pathways, which have been proposed to merge at a near-native state. This
      species contains stable structure in the alpha- and beta-domains but lacks a
      functional active site. Although previous experiments have demonstrated that the
      near-native state is populated on the fast refolding pathway, its relevance to
      slow refolding molecules could not be directly determined from previous
      experiments. In this paper, we describe experiments that investigate the effect
      of added salts on the refolding pathway of lysozyme at pH 5.2, 20 degrees C. We
      show, using stopped flow tryptophan fluorescence, inhibitor binding, and circular
      dichroism (CD), that the rate of formation of native lysozyme on the slow
      refolding track is significantly reduced in solutions of high ionic strength in a
      manner dependent on the position of the anion in the Hofmeister series. By
      contrast, the rate of evolution of hydrogen exchange (HX) protection monitored by
      electrospray ionization mass spectrometry (ESI MS) is unchanged under the
      refolding conditions studied. The data show, therefore, that at high ionic
      strengths beta-domain stabilization and native state formation on the slow
      refolding pathway become kinetically decoupled such that the near-native state
      becomes significantly populated. Thus, by changing the energy landscape with the
      addition of salts new insights into the relevance of intermediate states in
      lysozyme refolding are revealed.

PMID- 10210183
TI  - Protein-protein recognition: an experimental and computational study of the R89K
      mutation in Raf and its effect on Ras binding.
AB  - Binding of the protein Raf to the active form of Ras promotes activation of the
      MAP kinase signaling pathway, triggering cell growth and differentiation.
      Raf/Arg89 in the center of the binding interface plays an important role
      determining Ras-Raf binding affinity. We have investigated experimentally and
      computationally the Raf-R89K mutation, which abolishes signaling in vivo. The
      binding to [gamma-35S]GTP-Ras of a fusion protein between the Raf-binding domain
      (RBD) of Raf and GST was reduced at least 175-fold by the mutation, corresponding
      to a standard binding free energy decrease of at least 3.0 kcal/mol. To compute
      this free energy and obtain insights into the microscopic interactions favoring
      binding, we performed alchemical simulations of the RBD, both complexed to Ras
      and free in solution, in which residue 89 is gradually mutated from Arg into Lys.
      The simulations give a standard binding free energy decrease of 2.9+/-1.9
      kcal/mol, in agreement with experiment. The use of numerous runs with three
      different force fields allows insights into the sources of uncertainty in the
      free energy and its components. The binding decreases partly because of a 7
      kcal/mol higher cost to desolvate Lys upon binding, compared to Arg, due to
      better solvent interactions with the more concentrated Lys charge in the unbound
      state. This effect is expected to be general, contributing to the lower
      propensity of Lys to participate in protein-protein interfaces. Large
      contributions to the free energy change also arise from electrostatic
      interactions with groups up to 8 A away, namely residues 37-41 in the conserved
      effector domain of Ras (including 4 kcal/mol from Ser39 which loses a bifurcated
      hydrogen bond to Arg89), the conserved Lys84 and Lys87 of Raf, and 2-3 specific
      water molecules. This analysis will provide insights into the large experimental
      database of Ras-Raf mutations.

PMID- 10210184
TI  - Interaction of thioredoxins with target proteins: role of particular structural
      elements and electrostatic properties of thioredoxins in their interplay with 2
      oxoacid dehydrogenase complexes.
AB  - The thioredoxin action upon the 2-oxoacid dehydrogenase complexes is investigated
      by using different thioredoxins, both wild-type and mutated. The attacking
      cysteine residue of thioredoxin is established to be essential for the
      thioredoxin-dependent activation of the complexes. Mutation of the buried
      cysteine residue to serine is not crucial for the activation, but prevents
      inhibition of the complexes, exhibited by the Clamydomonas reinhardtii
      thioredoxin m disulfide. Site-directed mutagenesis of D26, W31, F/W12, and Y/A70
      (the Escherichia coli thioredoxin numbering is employed for all the thioredoxins
      studied) indicates that both the active site and remote residues of thioredoxin
      are involved in its interplay with the 2-oxoacid dehydrogenase complexes.
      Sequences of 11 thioredoxin species tested biochemically are aligned. The
      thioredoxin residues at the contact between the alpha3/3(10) and alpha1 helices,
      the length of the alpha1 helix and the charges in the alpha2-beta3 and beta4
      beta5 linkers are found to correlate with the protein influence on the 2-oxoacid
      dehydrogenase complexes (the secondary structural elements of thioredoxin are
      defined according to Eklund H et al., 1991, Proteins 11:13-28). The distribution
      of the charges on the surface of the thioredoxin molecules is analyzed. The
      analysis reveals the species specific polarization of the thioredoxin active site
      surroundings, which corresponds to the efficiency of the thioredoxin interplay
      with the 2-oxoacid dehydrogenase systems. The most effective mitochondrial
      thioredoxin is characterized by the strongest polarization of this area and the
      highest value of the electrostatic dipole vector of the molecule. Not only the
      magnitude, but also the orientation of the dipole vector show correlation with
      the thioredoxin action. The dipole direction is found to be significantly
      influenced by the charges of the residues 13/14, 51, and 83/85, which distinguish
      the activating and inhibiting thioredoxin disulfides.

PMID- 10210185
TI  - Functional implications of structural differences between variants A and B of
      bovine beta-lactoglobulin.
AB  - The structure of the trigonal crystal form of bovine beta-lactoglobulin variant B
      at pH 7.1 has been determined by X-ray diffraction methods at a resolution of
      2.22 A and refined to values for R and Rfree of 0.239 and 0.286, respectively. By
      comparison with the structure of the trigonal crystal form of bovine beta
      lactoglobulin variant A at pH 7.1, which was determined previously [Qin BY et
      al., 1998, Biochemistry 37:14014-14023], the structural consequences of the
      sequence differences D64G and V118A of variants A and B, respectively, have been
      investigated. Only minor differences in the core calyx structure occur. In the
      vicinity of the mutation site D64G on loop CD (residues 61-67), there are small
      changes in main-chain conformation, whereas the substitution V118A on beta-strand
      H is unaccompanied by changes in the surrounding structure, thereby creating a
      void volume and weakened hydrophobic interactions with a consequent loss of
      thermal stability relative to variant A. A conformational difference is found for
      the loop EF, implicated in the pH-dependent conformational change known as the
      Tanford transition, but it is not clear whether this reflects differences
      intrinsic to the variants in solution or differences in crystallization.

PMID- 10210186
TI  - Crystal structure of a designed, thermostable, heterotrimeric coiled coil.
AB  - Electrostatic interactions are often critical for determining the specificity of
      protein-protein complexes. To study the role of electrostatic interactions for
      assembly of helical bundles, we previously designed a thermostable,
      heterotrimeric coiled coil, ABC, in which charged residues were employed to drive
      preferential association of three distinct, 34-residue helices. To investigate
      the basis for heterotrimer specificity, we have used multiwavelength anomalous
      diffraction (MAD) analysis to determine the 1.8 A resolution crystal structure of
      ABC. The structure shows that ABC forms a heterotrimeric coiled coil with the
      intended arrangement of parallel chains. Over half of the ion pairs engineered to
      restrict helix associations were apparent in the experimental electron density
      map. As seen in other trimeric coiled coils, ABC displays acute knobs-into-holes
      packing and a buried anion coordinated by core polar amino acids. These
      interactions validate the design strategy and illustrate how packing and polar
      contacts determine structural uniqueness.

PMID- 10210187
TI  - The crystal structure of alpha-thrombin-hirunorm IV complex reveals a novel
      specificity site recognition mode.
AB  - The X-ray crystal structure of the human alpha-thrombin-hirunorm IV complex has
      been determined at 2.5 A resolution, and refined to an R-factor of 0.173. The
      structure reveals an inhibitor binding mode distinctive of a true hirudin
      mimetic, which justifies the high inhibitory potency and the selectivity of
      hirunorm IV. This novel inhibitor, composed of 26 amino acids, interacts through
      the N-terminal end with the alpha-thrombin active site in a nonsubstrate mode,
      and binds specifically to the fibrinogen recognition exosite through the C
      terminal end. The backbone of the N-terminal tripeptide Chg1"-Arg2"-2Na13" (Chg,
      cyclohexyl-glycine; 2Na1, beta-(2-naphthyl)-alanine) forms a parallel beta-strand
      to the thrombin main-chain segment Ser214-Gly216. The Chg1" side chain occupies
      the S2 site, Arg2" penetrates into the S1 specificity site, while the 2Na13" side
      chain occupies the aryl binding site. The Arg2" side chain enters the S1
      specificity pocket from a position quite apart from the canonical P1 site. This
      notwithstanding, the Arg2" side chain establishes the typical ion pair with the
      carboxylate group of Asp189.

PMID- 10210188
TI  - On the role of the cis-proline residue in the active site of DsbA.
AB  - In addition to the Cys-Xaa-Xaa-Cys motif at position 30-33, DsbA, the essential
      catalyst for disulfide bond formation in the bacterial periplasm shares with
      other oxidoreductases of the thioredoxin family a cis-proline in proximity of the
      active site residues. In the variant DsbA(P151A), this residue has been changed
      to an alanine, an almost isosteric residue which is not disposed to adopt the cis
      conformation. The substitution strongly destabilized the structure of DsbA, as
      determined by the decrease in the free energy of folding. The pKa of the thiol of
      Cys30 was only marginally decreased. Although in vivo the variant appeared to be
      correctly oxidized, it exhibited an activity less than half that of the wild-type
      enzyme with respect to the folding of alkaline phosphatase, used as a reporter of
      the disulfide bond formation in the periplasm. DsbA(P151A) crystallized in a
      different crystal form from the wild-type protein, in space group P2(1) with six
      molecules in the asymmetric unit. Its X-ray structure was determined to 2.8 A
      resolution. The most significant conformational changes occurred at the active
      site. The loop 149-152 adopted a new backbone conformation with Ala151 in a trans
      conformation. This rearrangement resulted in the loss of van der Waals
      interactions between this loop and the disulfide bond. His32 from the Cys-Xaa-Xaa
      Cys sequence presented in four out of six molecules in the asymmetric unit a
      gauche conformation not observed in the wild-type protein. The X-ray structure
      and folding studies on DsbA(P151A) were consistent with the cis-proline playing a
      major role in the stabilization of the protein. A role for the positioning of the
      substrate is discussed. These important properties for the enzyme function might
      explain the conservation of this residue in DsbA and related proteins possessing
      the thioredoxin fold.

PMID- 10210189
TI  - On the non-respect of the thermodynamic cycle by DsbA variants.
AB  - The mechanism of the disulfide-bond forming enzyme DsbA depends on the very low
      pKa of a cysteine residue in its active-site and on the relative instability of
      the oxidized enzyme compared to the reduced one. A thermodynamic cycle has been
      used to correlate its redox properties to the difference in the free energies of
      folding (deltadeltaGred/ox) of the oxidized and reduced forms. However, the
      relation was proved unsatisfied for a number of DsbA variants. In this study, we
      investigate the thermodynamic and redox properties of a highly destabilized
      variant DsbA(P151A) (substitution of cis-Pro151 by an alanine) by the means of
      intrinsic tryptophan fluorescence and by high-sensitivity differential scanning
      calorimetry (HS-DSC). When the value of deltadeltaGred/ox obtained
      fluorimetrically for DsbA(P151A) does not correlate with the value expected from
      its redox potential, the value of deltadeltaGred/ox provided by HS-DSC are in
      perfect agreement with the predicted thermodynamic cycle for both wild-type and
      variant. HS-DSC data indicate that oxidized wild-type enzyme and the reduced
      forms of both wild-type and variant unfold according to a two-state mechanism.
      Oxidized DsbA(P151A) shows a deviation from two-state behavior that implies the
      loss of interdomain cooperativity in DsbA caused by Pro151 substitution. The
      presence of chaotrope in fluorimetric measurements could facilitate domain
      uncoupling so that the fluorescence probe (Trp76) does not reflect the whole
      unfolding process of DsbA(P151A) anymore. Thus, theoretical thermodynamic cycle
      is respected when an appropriate method is applied to DsbA unfolding under
      conditions in which protein domains still conserve their cooperativity.

PMID- 10210190
TI  - Substitution of the methionine residues of calmodulin with the unnatural amino
      acid analogs ethionine and norleucine: biochemical and spectroscopic studies.
AB  - Calmodulin (CaM) is a 148-residue regulatory calcium-binding protein that
      activates a wide range of target proteins and enzymes. Calcium-saturated CaM has
      a bilobal structure, and each domain has an exposed hydrophobic surface region
      where target proteins are bound. These two "active sites" of calmodulin are
      remarkably rich in Met residues. Here we have biosynthetically substituted (up to
      90% incorporation) the unnatural amino acids ethionine (Eth) and norleucine (Nle)
      for the nine Met residues of CaM. The substituted proteins bind in a calcium
      dependent manner to hydrophobic matrices and a synthetic peptide, encompassing
      the CaM-binding domain of myosin light-chain kinase (MLCK). Infrared and circular
      dichroism spectroscopy show that there are essentially no changes in the
      secondary structure of these proteins compared to wild-type CaM (WT-CaM). One-
      and two-dimensional NMR studies of the Eth-CaM and Nle-CaM proteins reveal that,
      while the core of the proteins is relatively unaffected by the substitutions, the
      two hydrophobic interaction surfaces adjust to accommodate the Eth and Nle
      residues. Enzyme activation studies with MLCK show that Eth-CaM and Nle-CaM
      activate the enzyme to 90% of its maximal activity, with little changes in
      dissociation constant. For calcineurin only 50% activation was obtained, and the
      K(D) for Nle-CaM also increased 3.5-fold compared with WT-CaM. These data show
      that the "active site" Met residues of CaM play a distinct role in the activation
      of different target enzymes, in agreement with site-directed mutagenesis studies
      of the Met residues of CaM.

PMID- 10210191
TI  - Structural comparisons of TIM barrel proteins suggest functional and evolutionary
      relationships between beta-galactosidase and other glycohydrolases.
AB  - Beta-galactosidase (lacZ) from Escherichia coli is a 464 kDa homotetramer. Each
      subunit consists of five domains, the third being an alpha/beta barrel that
      contains most of the active site residues. A comparison is made between each of
      the domains and a large set of proteins representative of all structures from the
      protein data bank. Many structures include an alpha/beta barrel. Those that are
      most similar to the alpha/beta barrel of E. coli beta-galactosidase have similar
      catalytic residues and belong to the so-called "4/7 superfamily" of glycosyl
      hydrolases. The structure comparison suggests that beta-amylase should also be
      included in this family. Of three structure comparison methods tested, the
      "ProSup" procedure of Zu-Kang and Sippl and the "Superimpose" procedure of
      Diederichs were slightly superior in discriminating the members of this
      superfamily, although all procedures were very powerful in identifying related
      protein structures. Domains 1, 2, and 4 of E. coli beta-galactosidase have
      topologies related to "jelly-roll barrels" and "immunoglobulin constant" domains.
      This fold also occurs in the cellulose binding domains (CBDs) of a number of
      glycosyl hydrolases. The fold of domain 1 of E. coli beta-galactosidase is
      closely related to some CBDs, and the domain contributes to substrate binding,
      but in a manner unrelated to cellulose binding by the CBDs. This is typical of
      domains 1, 2, 4, and 5, which appear to have been recruited to play roles in beta
      galactosidase that are unrelated to the functions that such domains provide in
      other contexts. It is proposed that beta-galactosidase arose from a prototypical
      single domain alpha/beta barrel with an extended active site cleft. The
      subsequent incorporation of elements from other domains could then have reduced
      the size of the active site from a cleft to a pocket to better hydrolyze the
      disaccharide lactose and, at the same time, to facilitate the production of
      inducer, allolactose.

PMID- 10210192
TI  - Relationships within the aldehyde dehydrogenase extended family.
AB  - One hundred-forty-five full-length aldehyde dehydrogenase-related sequences were
      aligned to determine relationships within the aldehyde dehydrogenase (ALDH)
      extended family. The alignment reveals only four invariant residues: two
      glycines, a phenylalanine involved in NAD binding, and a glutamic acid that
      coordinates the nicotinamide ribose in certain E-NAD binary complex crystal
      structures, but which may also serve as a general base for the catalytic
      reaction. The cysteine that provides the catalytic thiol and its closest neighbor
      in space, an asparagine residue, are conserved in all ALDHs with demonstrated
      dehydrogenase activity. Sixteen residues are conserved in at least 95% of the
      sequences; 12 of these cluster into seven sequence motifs conserved in almost all
      ALDHs. These motifs cluster around the active site of the enzyme. Phylogenetic
      analysis of these ALDHs indicates at least 13 ALDH families, most of which have
      previously been identified but not grouped separately by alignment. ALDHs cluster
      into two main trunks of the phylogenetic tree. The largest, the "Class 3" trunk,
      contains mostly substrate-specific ALDH families, as well as the class 3 ALDH
      family itself. The other trunk, the "Class 1/2" trunk, contains mostly variable
      substrate ALDH families, including the class 1 and 2 ALDH families. Divergence of
      the substrate-specific ALDHs occurred earlier than the division between ALDHs
      with broad substrate specificities. A site on the World Wide Web has also been
      devoted to this alignment project.

PMID- 10210193
TI  - Mechanics and dynamics of B1 domain of protein G: role of packing and surface
      hydrophobic residues.
AB  - The structural organization of the B1 domain of streptococcal protein G (PGA) has
      been probed using molecular dynamics simulations, with a particular emphasis on
      the role of the solvent exposed Ile6 residue. In addition to the native protein
      (WT-PGA), three single-mutants (I6G-PGA, I6F-PGA, and I6T-PGA), one double-mutant
      (I6T,T53G-PGA), and three isolated peptide fragments (corresponding to the helix
      and the two beta-hairpins) were studied in the presence of explicit water
      molecules. Comparative analysis of the various systems showed that the level of
      perturbation was directly related to the hydrophobicity and the size of the side
      chain of residue 6, the internal rigidity of the proteins decreasing in the order
      I6T-PGA > I6G-PGA > WT-PGA > I6F-PGA. The results emphasized the importance of
      residue 6 in controlling both the integrity of the sheet's surface and the
      orientation of the helix in relation to the sheet by modulation of surface/core
      interactions. The effects of mutations were delocalized across the structure, and
      glycine residues, in particular, absorbed most of the introduced strain. A
      qualitative structural decomposition of the native fold into elementary building
      blocks was achieved using principal component analysis and mechanical response
      matrices. Within this framework, internal motions of the protein were described
      as coordinated articulations of these structural units, mutations affecting
      mostly the amplitude of the motions rather than the structure/location of the
      building-blocks. Analysis of the isolated peptidic fragments suggested that
      packing did not play a determinant role in defining the elementary building
      blocks, but that chain topology was mostly responsible.

PMID- 10210194
TI  - Association of partially-folded intermediates of staphylococcal nuclease induces
      structure and stability.
AB  - Staphylococcal nuclease forms three different partially-folded intermediates at
      low pH in the presence of low to moderate concentration of anions, differing in
      the amount of secondary structure, globularity, stability, and compactness.
      Although these intermediates are monomeric at low protein concentration (< or
      =0.25 mg/mL), increasing concentrations of protein result in the formation of
      dimers and soluble oligomers, ultimately leading to larger insoluble aggregates.
      Unexpectedly, increasing protein concentration not only led to association, but
      also to increased structure of the intermediates. The secondary structure,
      stability, and globularity of the two less-ordered partially-folded intermediates
      (A1 and A2) were substantially increased upon association, suggesting that
      aggregation induces structure. An excellent correlation was found between degree
      of association and amount of structure measured by different techniques,
      including circular dichroism, fluorescence, Fourier transform infrared
      spectroscopy (FTIR), and small-angle X-ray scattering. The associated states were
      also substantially more stable toward urea denaturation than the monomeric forms.
      A mechanism is proposed, in which the observed association of monomeric
      intermediates involves intermolecular interactions which correspond to those
      found intramolecularly in normal folding to the native state.

PMID- 10210195
TI  - The Mycobacterium tuberculosis small heat shock protein Hsp16.3 exposes
      hydrophobic surfaces at mild conditions: conformational flexibility and molecular
      chaperone activity.
AB  - Hsp16.3, the alpha-crystallin-related small heat shock protein of Mycobacterium
      tuberculosis that is maximally expressed during the stationary phase and is a
      major membrane protein, has been reported to form specific trimer-of-trimers
      structure and to act as an effective molecular chaperone (Chang Z et al., 1996,
      J. Biol Chem 271:7218-7223). However, little is known about its action mechanism.
      In this study, Hsp16.3 conformational intermediates with dramatically increased
      chaperone activities were detected after treatment with very low concentrations
      of guanidine hydrochloride (0.05 M), urea (0.3 M), or mild heating (30 degrees
      C). The intermediates showed a significant increase in their capacity to bind the
      hydrophobic probe 1-anilino-8-naphthalene sulfonate (ANS), indicating an
      increased exposure of hydrophobic surfaces. Interestingly, the greatest chaperone
      activities of Hsp16.3 were observed in the presence of 0.3 M guanidine HCl or
      when heated to 35 degrees C. CD spectroscopy studies revealed no significant
      changes in protein secondary and tertiary structures at these mild treatments.
      Our in vitro studies also indicate that long-time-heated Hsp16.3, heated even to
      temperatures as high as 85 degrees C, has almost the same, if not a slightly
      greater, chaperone activities as the native protein when cooled to room
      temperature and its secondary structures also almost recovered. Together, these
      results suggest that Hsp16.3 modulates its chaperone activity by exposing
      hydrophobic surfaces and that the protein structure is highly stable and
      flexible, thus highly adapted for its function.

PMID- 10210197
TI  - Folding simulation of protein models on the structure-based cubo-octahedral
      lattice with the Contact Interactions algorithm.
AB  - Computer simulations of protein models on lattices have been widely used as an
      aid in the study of protein folding process. Following the suggestion of
      Raghunathan and Jernigan (1997, Protein Sci. 6:2072-2083) that the cubooctahedral
      lattice can allow a more realistic representation of proteins than other
      lattices, we propose here the use of a new set of internal coordinates theta for
      the description of a protein model on this lattice. An easy procedure for the
      conversion of the theta coordinates to the Cartesian coordinates is also
      described. When the Contact Interaction approach, already proposed by us for
      simulations on square or cubic lattices, was applied to the cubo-octahedral
      lattice, the system obeyed the correct thermodynamics derived from the definition
      of energy. Thus, lattice simulations of protein models, in which secondary
      structure elements such as alpha-helices or beta-strands can be easily
      identifiable, can be performed.

PMID- 10210199
TI  - Stereoselectivity of Mucorales lipases toward triradylglycerols--a simple
      solution to a complex problem.
AB  - The lipases from Rhizopus and Rhizomucor are members of the family of Mucorales
      lipases. Although they display high sequence homology, their stereoselectivity
      toward triradylglycerols (sn-2 substituted triacylglycerols) varies. Four
      different triradylglycerols were investigated, which were classified into two
      groups: flexible substrates with rotatable O'-C1' ether or ester bonds adjacent
      to C2 of glycerol and rigid substrates with a rigid N'-C1' amide bond or a phenyl
      ring in sn-2. Although Rhizopus lipase shows opposite stereopreference for
      flexible and rigid substrates (hydrolysis in sn-1 and sn-3, respectively),
      Rhizomucor lipase hydrolyzes both groups of triradylglycerols preferably in sn-1.
      To explain these experimental observations, computer-aided molecular modeling was
      applied to study the molecular basis of stereoselectivity. A generalized model
      for both lipases of the Mucorales family highlights the residues mediating
      stereoselectivity: (1) L258, the C-terminal neighbor of the catalytic histidine,
      and (2) G266, which is located in a loop contacting the glycerol backbone of a
      bound substrate. Interactions with triradylglycerol substrates are dominated by
      van der Waals contacts. Stereoselectivity can be predicted by analyzing the value
      of a single substrate torsion angle that discriminates between sn-1 and sn-3
      stereopreference for all substrates and lipases investigated here. This simple
      model can be easily applied in enzyme and substrate engineering to predict
      Mucorales lipase variants and synthetic substrates with desired
      stereoselectivity.

PMID- 10210196
TI  - Thermodynamic linkage between the binding of protons and inhibitors to HIV-1
      protease.
AB  - The aspartyl dyad of free HIV-1 protease has apparent pK(a)s of approximately 3
      and approximately 6, but recent NMR studies indicate that the aspartyl dyad is
      fixed in the doubly protonated form over a wide pH range when cyclic urea
      inhibitors are bound, and in the monoprotonated form when the inhibitor KNI-272
      is bound. We present computations and measurements related to these changes in
      protonation and to the thermodynamic linkage between protonation and inhibition.
      The Poisson-Boltzmann model of electrostatics is used to compute the apparent
      pK(a)s of the aspartyl dyad in the free enzyme and in complexes with four
      different inhibitors. The calculations are done with two parameter sets. One
      assigns epsilon = 4 to the solute interior and uses a detailed model of
      ionization; the other uses epsilon = 20 for the solute interior and a simplified
      representation of ionization. For the free enzyme, both parameter sets agree well
      with previously measured apparent pK(a)s of approximately 3 and approximately 6.
      However, the calculations with an internal dielectric constant of 4 reproduce the
      large pKa shifts upon binding of inhibitors, but the calculations with an
      internal dielectric constant of 20 do not. This observation has implications for
      the accurate calculation of pK(a)s in complex protein environments. Because
      binding of a cyclic urea inhibitor shifts the pK(a)s of the aspartyl dyad,
      changing the pH is expected to change its apparent binding affinity. However, we
      find experimentally that the affinity is independent of pH from 5.5 to 7.0.
      Possible explanations for this discrepancy are discussed.

PMID- 10210198
TI  - The influence of C-terminal extension on the structure of the "J-domain" in E.
      coli DnaJ.
AB  - Two different recombinant constructs of the N-terminal domain in Escherichia coli
      DnaJ were uniformly labeled with nitrogen-15 and carbon-13. One, DnaJ(1-78),
      contains the complete "J-domain," and the other, DnaJ(1-104), contains both the
      "J-domain" and a conserved "G/F" extension at the C-terminus. The three
      dimensional structures of these proteins have been determined by heteronuclear
      NMR experiments. In both proteins the "J-domain" adopts a compact structure
      consisting of a helix-turn-helix-loop-helix-turn-helix motif. In contrast, the
      "G/F" region in DnaJ(1-104) does not fold into a well-defined structure.
      Nevertheless, the "G/F" region has been found to have an effect on the packing of
      the helices in the "J-domain" in DnaJ(1-104). Particularly, the interhelical
      angles between Helix IV and other helices are significantly different in the two
      structures. In addition, there are some local conformational changes in the loop
      region connecting the two central helices. These structural differences in the "J
      domain" in the presence of the "G/F" region may be related to the observation
      that DnaJ (1-78) is incapable of stimulating the ATPase activity of the molecular
      chaperone protein DnaK despite evidence that sites mediating the binding of DnaJ
      to DnaK are located in the 1-78 segment.

PMID- 10210200
TI  - A mechanistic analysis of the increase in the thermal stability of proteins in
      aqueous carboxylic acid salt solutions.
AB  - The stability of proteins is known to be affected significantly in the presence
      of high concentration of salts and is highly pH dependent. Extensive studies have
      been carried out on the stability of proteins in the presence of simple
      electrolytes and evaluated in terms of preferential interactions and increase in
      the surface tension of the medium. We have carried out an in-depth study of the
      effects of a series of carboxylic acid salts: ethylene diamine tetra acetate,
      butane tetra carboxylate, propane tricarballylate, citrate, succinate, tartarate,
      malonate, and gluconate on the thermal stability of five different proteins that
      vary in their physico-chemical properties: RNase A, cytochrome c, trypsin
      inhibitor, myoglobin, and lysozyme. Surface tension measurements of aqueous
      solutions of the salts indicate an increase in the surface tension of the medium
      that is very strongly correlated with the increase in the thermal stability of
      proteins. There is also a linear correlation of the increase in thermal stability
      with the number of carboxylic groups in the salt. Thermal stability has been
      found to increase by as much as 22 C at 1 M concentration of salt. Such a high
      thermal stability at identical concentrations has not been reported before. The
      differences in the heat capacities of denaturation, deltaCp for RNase A, deduced
      from the transition curves obtained in the presence of varying concentrations of
      GdmCl and that of carboxylic acid salts as a function of pH, indicate that the
      nature of the solvent medium and its interactions with the two end states of the
      protein control the thermodynamics of protein denaturation. Among the physico
      chemical properties of proteins, there seems to be an interplay of the
      hydrophobic and electrostatic interactions that lead to an overall stabilizing
      effect. Increase in surface free energy of the solvent medium upon addition of
      the carboxylic acid salts appears to be the dominant factor in governing the
      thermal stability of proteins.

PMID- 10210201
TI  - Identification of Tyr438 as the major in vitro c-Src phosphorylation site in
      human gelsolin: a mass spectrometric approach.
AB  - Gelsolin is an actin-binding protein (82 kDa) consisting of six repeated segments
      (S1-S6), each approximately 120 residues long. It interacts with phospholipids
      and we previously showed that phosphatidylinositol 4,5-bisphosphate promotes
      phosphorylation of gelsolin by the tyrosine kinase c-Src. We used a combination
      of different methods, such as thin-layer chromatography and anti-phosphotyrosine
      agarose immunoprecipitation of phosphopeptides combined with matrix assisted
      laser desorption ionization-mass spectrometry (MALDI-MS) and post source decay
      (PSD) analysis, to identify the phosphorylation sites in gelsolin. The major
      phosphorylation site (Tyr438) was located in subdomain 4 (S4). Phosphorylation of
      gelsolin in the gelsolin-actin2 complex was inhibited by 90%. Gelsolin
      phosphorylation by c-Src in the presence of lysophosphatidic acid also revealed
      Tyr438 as the most prominent site. Additional minor sites were found using the
      anti-phosphotyrosine bead immunoprecipitation method followed by MALDI-MS and PSD
      analysis. These sites, representing approximately 5% of the total phosphate
      incorporation, were identified as Tyr59, Tyr382, Tyr576, and Tyr624. Based on
      these results we generated antibodies which specifically recognize Tyr438
      phosphorylated gelsolin.

PMID- 10210202
TI  - The insect immune protein scolexin is a novel serine proteinase homolog.
AB  - Scolexin is a coagulation-provoking plasma protein induced in response to
      bacterial or viral infection of larval Manduca sexta, a large lepidopterous
      insect. Here we report the isolation and sequencing of two cDNA clones that code
      for scolexin isoforms sharing 80% sequence identity. The scolexin sequences have
      low but recognizable sequence similarity to members of the chymotrypsin family
      and represent a new subfamily of chymotrypsin-like serine proteinases. Comparison
      with known structures reveals the conservation of key catalytic residues and a
      possible specificity for small nonpolar residues. Most remarkable is the absence
      of a canonical activation peptide cleavage site. This suggests that the
      regulation of scolexin activity will involve a novel activation mechanism.

PMID- 10210203
TI  - Structural consequences of the active site substitution Cys181 ==> Ser in metallo
      beta-lactamase from Bacteroides fragilis.
AB  - The metallo-beta-lactamases require divalent cations such as zinc or cadmium for
      hydrolyzing the amide bond of beta-lactam antibiotics. The crystal structure of
      the Zn2+ -bound enzyme from Bacteroides fragilis contains a binuclear zinc center
      in the active site. A hydroxide, coordinated to both zinc atoms, is proposed as
      the moiety that mounts the nucleophilic attack on the carbonyl carbon atom of the
      beta-lactam bond of the substrate. It was previously reported that the
      replacement of the active site Cys181 by a serine residue severely impaired
      catalysis while atomic absorption measurements indicated that binding of the two
      zinc ions remained intact. Contradicting data emerge from recent mass
      spectrometry results, which show that only a single zinc ion binds to the C181S
      metallo-beta-lactamase. In the current study, the C181S mutant enzyme was
      examined at the atomic level by determining the crystal structure at 2.6 A
      resolution. The overall structure of the mutant enzyme is the same as that of the
      wild-type enzyme. At the mutation site, the side chain of Ser181 occupies the
      same position as that of the side chain of Cys181 in the wild-type protein. One
      zinc ion, Zn1, is present in the crystal structure; however, the site of the
      second zinc ion, Zn2 is unoccupied. A water molecule is associated with Zn1,
      reminiscent of the hydroxide seen in the structure of the wild-type enzyme but
      farther from the metal. The position of the water molecule is off the plane of
      the carboxylate group of Asp103; therefore, the water molecule may be less
      nucleophilic than a water molecule which is coplanar with the carboxylate group.

PMID- 10210205
TI  - NIH expands imaging research opportunities.

PMID- 10210206
TI  - How cesium-137 was discovered by an undergraduate student.

PMID- 10210204
TI  - Comparison of anionic and cationic trypsinogens: the anionic activation domain is
      more flexible in solution and differs in its mode of BPTI binding in the crystal
      structure.
AB  - Unlike bovine cationic trypsin, rat anionic trypsin retains activity at high pH.
      This alkaline stability has been attributed to stabilization of the salt bridge
      between the N-terminal Ile16 and Asp194 by the surface negative charge (Soman K,
      Yang A-S, Honig B, Fletterick R., 1989, Biochemistry 28:9918-9926). The formation
      of this salt bridge controls the conformation of the activation domain in
      trypsin. In this work we probe the structure of rat trypsinogen to determine the
      effects of the surface negative charge on the activation domain in the absence of
      the Ile16-Asp194 salt bridge. We determined the crystal structures of the rat
      trypsin-BPTI complex and the rat trypsinogen-BPTI complex at 1.8 and 2.2 A,
      respectively. The BPTI complex of rat trypsinogen resembles that of rat trypsin.
      Surprisingly, the side chain of Ile16 is found in a similar position in both the
      rat trypsin and trypsinogen complexes, although it is not the N-terminal residue
      and cannot form the salt bridge in trypsinogen. The resulting position of the
      activation peptide alters the conformation of the adjacent autolysis loop
      (residues 142-153). While bovine trypsinogen and trypsin have similar CD spectra,
      the CD spectrum of rat trypsinogen has only 60% of the intensity of rat trypsin.
      This lower intensity most likely results from increased flexibility around two
      conserved tryptophans, which are adjacent to the activation domain. The NMR
      spectrum of rat trypsinogen contains high field methyl signals as observed in
      bovine trypsinogen. It is concluded that the activation domain of rat trypsinogen
      is more flexible than that of bovine trypsinogen, but does not extend further
      into the protein core.

PMID- 10210208
TI  - Thallium-gated SPECT in patients with major myocardial infarction: effect of
      filtering and zooming in comparison with equilibrium radionuclide imaging and
      left ventriculography.
AB  - The effect of filtering and zooming on 201TI-gated SPECT was evaluated in
      patients with major myocardial infarction. METHODS: Rest thallium (TI)-gated
      SPECT was performed with a 90 degrees dual-head camera, 4 h after injection of
      185 MBq 201TI in 32 patients (mean age 61 +/- 11 y) with large myocardial
      infarction (33% +/- 17% defect on bull's eye). End diastolic volume (EDV), end
      systolic volume (ESV) and left ventricular ejection fraction (LVEF) were
      calculated using a commercially available semiautomatic validated software.
      First, images were reconstructed using a 2.5 zoom, a Butterworth filter (order =
      5) and six Nyquist cutoff frequencies: 0.13 (B5.13), 0.15 (B5.15), 0.20 (B5.20),
      0.25 (B5.25), 0.30 (B5.30) and 0.35 (B5.35). Second, images were reconstructed
      using a zoom of 1 and a Butterworth filter (order = 5) (cutoff frequency 0.20
      [B5.20Z1]) (total = 32 x 7 = 224 reconstructions). LVEF was calculated in all
      patients using equilibrium radionuclide angiocardiography (ERNA). EDV, ESV and
      LVEF were measured with contrast left ventriculography (LVG). RESULTS: LVEF was
      39% +/- 2% (mean +/- SEM) for ERNA and 40% +/- 13% for LVG (P = 0.51). Gated
      SPECT with B5.20Z2.5 simultaneously offered a mean LVEF value (39% +/- 2%)
      similar to ERNA (39% +/- 2%) and LVG (40% +/- 3%), optimal correlations with both
      ERNA (r = 0.83) and LVG (r = 0.70) and minimal differences with both ERNA (-0.9%
      +/- 7.5% [mean +/- SD]) and LVG (1.1% +/- 10.5%). As a function of filter and
      zoom choice, correlation coefficients between ERNA or LVG LVEF, and gated SPECT
      ranged from 0.26 to 0.88; and correlation coefficients between LVG and gated
      SPECT volumes ranged from 0.87 to 0.94. There was a significant effect of
      filtering and zooming on EDV, ESV and LVEF (P < 0.0001). Low cutoff frequency
      (B5.13) overestimated LVEF (P < 0.0001 versus ERNA and LVG). Gated SPECT with 2.5
      zoom and high cutoff frequencies (B5.15, B5.20, B5.25, B5.30 and B5.35)
      overestimated EDV and ESV (P < 0.04) compared with LVG. This volume
      overestimation with TI-gated SPECT in patients with large myocardial infarction
      was correlated to the infarct size. A zoom of 1 underestimated EDV, ESV and LVEF
      compared with a 2.5 zoom (P < 0.02). CONCLUSION: Accurate LVEF measurement is
      possible with TI-gated SPECT in patients with major myocardial infarction.
      However, filtering and zooming greatly influence EDV, ESV and LVEF measurements,
      and TI-gated SPECT overestimates left ventricular volumes, particularly when the
      infarct size increases.

PMID- 10210207
TI  - Parametric polar maps of regional myocardial beta-adrenoceptor density.
AB  - Quantification of myocardial beta-adrenoceptor density (Bmax) is of interest in
      cardiac diseases in which altered function of the sympathetic nervous system is
      thought to play a pathophysiological role. PET provides an unrivaled means of
      taking regional measurements of cardiac microcirculatory function, tissue
      metabolism and autonomic nervous system activity. Measurements in small regional
      areas may be biased because of increased noise levels. This study examined the
      parametric polar map approach for the regional quantification of Bmax. METHODS:
      Dynamic PET with parametric polar map imaging was performed in 10 healthy
      volunteers and 4 patients with hypertrophic cardiomyopathy using (S)-[11C]-(4-(3
      tertiarybutylamino-2-hydroxypropoxy)-benzidimaz ole-2)-on hydrochloride (CGP)
      12177 and a double-injection protocol. Time-activity curves were corrected for
      partial volume, spill-over and wall motion effects. The mean Bmax of the left
      ventricle was calculated in two ways. First, the average time-activity curve of
      all segments, having the highest achievable signal-to-noise ratio, was used to
      calculate Bmax(mTAC) (the myocardial beta-adrenoceptor density of the left
      ventricle calculated using the average time-activity curve). The bias in
      Bmax(mTAC) introduced by noise is minimal. Second, an estimate of whole-heart
      receptor density was calculated using the polar map method by averaging the
      values of Bmax obtained for 576 individual segments. In these calculations, three
      different filters (3 x 5, 3 x 9 and 3 x 13 segments) were used to smooth the time
      activity curves before calculating Bmax. Mean values of whole-left-ventricular
      receptor density obtained by averaging regional values using the different
      filters (Bmax(PMF1/2/3)) were compared with Bmax(mTAC) to assess bias introduced
      by the polar map approach. Segments with a calculated Bmax outside the range 0.1
      50 pmol/g were considered unreliable and were excluded from the analysis.
      RESULTS: The differences between the two methods of calculating Bmax were small
      (7.8%, 4.8% and 3.2%, with the three filters, respectively). Reliable results
      were obtained in >95% of the segments and in 9 volunteers and all 4 patients.
      CONCLUSION: When using PET for the quantification of beta-adrenoceptor density,
      the regional variation in Bmax can be reliably assessed using the parametric
      polar map approach.

PMID- 10210209
TI  - 99mTc-HMPAO regional cerebral blood flow and quantitative electroencephalography
      in Alzheimer's disease: a correlative study.
AB  - In this study the neuropsychological status of patients with Alzheimer's disease
      (AD) was correlated with quantitative electroencephalography (qEEG) and regional
      cerebral blood flow (rCBF) both in the cortex and in deep gray matter structures.
      METHODS: Forty-three outpatients (mean age 72.4 +/- 7.5 y) with probable AD
      underwent 99mTc-hexamethyl propyleneamine oxime SPECT with a brain-dedicated
      gamma camera and qEEG (relative values) within 1 mo. Preliminary factorial
      analysis with promax rotation identified four qEEG bands (2-5.5, 6-7.5, 8-11.5
      and 12-22.5 Hz, with no distinction as to topography) and six SPECT regions (the
      two thalami together, the two parietal cortices together, the right temporal
      cortex, the right hippocampus, the left hippocampus and the remaining cortical
      areas together) as the variables with highest statistical power. All these
      variables and the Mini-Mental Status Examination score (MMSE, a sensitive marker
      of neuropsychological deficit) were processed by a final factorial analysis and
      multivariate analysis of variance. RESULTS: Both the 2-5.5 Hz and the 8-11.5 Hz
      powers were correlated with the perfusion level in the parietal regions of
      interest (ROls) (P = 0.0009), whereas the 2-5.5 Hz power was correlated with the
      right hippocampal perfusion level (P = 0.007). The MMSE score was significantly
      correlated with the perfusion level, both in the right (P = 0.006) and in the
      left (P = 0.004) hippocampal ROls and in the parietal ROls (P = 0.01); moreover,
      it was correlated with both the 2-5.5 Hz (P = 0.0005) and the 8-11.5 Hz (P =
      0.004) power. CONCLUSION: rCBF (bilateral parietal perfusion) and qEEG
      (especially the slowest frequencies, i.e., 2-5.5 Hz) are confirmed to be good
      descriptors of AD severity. It is especially noteworthy that bilateral
      hippocampal CBF was the perfusional index best correlated with the MMSE as well
      as being significantly correlated to qEEG. Hippocampal SPECT imaging appears to
      be a promising index to improve characterization of AD in respect to other forms
      of primary degenerative dementia and may be proposed as a marker for evaluating
      the effects of pharmacotherapy of AD at the neuronal level.

PMID- 10210210
TI  - Functional morphometry of the striatum in Parkinson's disease on three
      dimensional surface display of 123I-beta-CIT SPECT data.
AB  - The purpose of this study was to evaluate whether striatal morphology on a three
      dimensional surface display of 123I-2beta-carbomethoxy-3beta-(4
      iodophenyl)tropane (123I-beta-CIT) SPECT data can be used as a diagnostic index
      for Parkinson's disease. METHODS: We studied 11 patients with mild Parkinson's
      disease and 21 age-matched controls. Triple-head SPECT scans were acquired for 30
      min at 20 h after injection of 123I-beta-CIT. We measured the vertical height of
      the caudate head (H) and the length of the long axis of the striatum (L) on the
      three-dimensional surface display generated from SPECT data. The morphometric
      index of the striatum was defined as L/H. The power of L/H to discriminate
      Parkinson's disease and control groups was evaluated by discriminant function
      analysis and was compared with that of region of interest (ROI)-based 123I-beta
      CIT binding measurements (V"3) and their ratios. RESULTS: The mean L/H ratios
      (ipsilateral/contralateral) to the most affected limbs were (33%/45%) lower in
      the Parkinson's disease group compared with the control group, respectively. All
      other ROI-based measures confirmed that dopamine transporter reductions were most
      severe in the contralateral posterior putamen (a 68% reduction in V"3). In 1
      patient with a subsequent clinical diagnosis of drug-induced parkinsonism, all
      SPECT measures were normal. The contralateral putamen contributed most to the
      discriminatory power, and the contralateral L/H showed the best discriminatory
      power of all SPECT measures. CONCLUSION: These results suggest that striatal
      morphology on a three-dimensional display of 123I-beta-CIT SPECT data provides
      information of diagnostic significance for Parkinson's disease. This morphometry
      can be done without requiring technically demanding ROI analysis, and thus this
      technique may be suitable for routine clinical use.

PMID- 10210211
TI  - Specificity of somatostatin receptor scintigraphy: a prospective study and
      effects of false-positive localizations on management in patients with
      gastrinomas.
AB  - Somatostatin receptor scintigraphy (SRS) is being increasingly used both for
      localization and, in some cases, diagnosis of various diseases. There are no
      prospective studies of its specificity or occurrence of false-positive results
      and their effects on management. This study was designed to address both of these
      issues. METHODS: Over a 40-mo period, 146 consecutive patients with Zollinger
      Ellison syndrome (ZES) undergoing 480 SRS examinations were studied
      prospectively. Patients were admitted at least yearly and underwent SRS as well
      as conventional imaging studies (ultrasonography, CT, MRI) and angiography, if
      necessary. All admissions were assigned to one of five different clinical
      categories in which imaging studies had different purposes. SRS localizations
      were classified as true-positive or false-positive based on preset criteria. A
      false-positive result was determined to change clinical management based on five
      preset criteria. RESULTS: Of all SRS examinations, 12% resulted in a false
      positive localization for a neuroendocrine tumor or its metastases, resulting in
      a sensitivity of 71%, specificity of 86% and positive and negative predictive
      values of 85% and 52%, respectively. Extra-abdominal false-positive localizations
      (2/3) were more common than intra-abdominal (1/3). Thyroid disease, breast
      disease and granulomatosis lung disease were the most frequent causes of extra
      abdominal false-positive localizations. Accessory spleens, localization to
      previous operative sites, renal parapelvic cysts and various procedural aspects
      were the most frequent causes of intra-abdominal false-positive localizations. Of
      all SRS studies, 2.7% resulted in a false-positive result that altered
      management. CONCLUSION: False-positive SRS localization occurs in 1 of 10
      patients with ZES. By having a thorough understanding of diseases or
      circumstances that result in false-positive localization and comparing the SRS
      result with the clinical context, the percentage of patients in whom false
      positive localization results in altered management can be reduced to below 3%
      and the correct diagnosis made in almost every case.

PMID- 10210212
TI  - Making the best of imperfect tumor-localizing radiopharmaceuticals.

PMID- 10210213
TI  - Glucose transporters and FDG uptake in untreated primary human non-small cell
      lung cancer.
AB  - PET imaging of malignant tumors with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose
      (FDG) as a tracer is a noninvasive diagnostic and prognostic tool that measures
      tumor metabolism. In this study, we assessed the relationships between FDG uptake
      and the expression of facilitative glucose transporters, the sizes of populations
      of proliferating cells and infiltrating macrophages in patients with primary non
      small cell lung cancers (NSCLC). METHODS: FDG uptake and the expression of five
      glucose transporters and the proportions of proliferating cell and macrophage
      populations were studied in paraffin sections from untreated primary lung cancers
      by immunohistochemistry. The patients were imaged with FDG PET before surgery.
      RESULTS: All tumors could be detected by FDG PET. Uptake was correlated with
      tumor size (P = 0.004). FDG uptake was lower in adenocarcinomas (ACs) than in
      squamous cell carcinomas (SQCs) (P = 0.03) or large cell carcinomas (P = 0.002)
      [standardized uptake value corrected for lean body mass (SUL) = 5.42 +/- 2.77,
      8.04 +/-3.25 and 10.42 +/- 4.54, respectively]. Glut-1 expression was
      significantly higher than that of any other transporter. All tumors tested (n =
      23) were Glut-1-positive (70.8% +/- 26.1% of tumor cell area was positive and
      staining intensity was 2.8 +/- 1.2). Glut-1 expression was higher in SQCs (78% +/
      17.8% and 3.5 +/-0.6) than in ACs (47.5% +/- 30.3% and 1.6 +/- 1.1; P = 0.044
      for positive tumor cell area and P = 0.005 for staining intensity). Proliferating
      cells constituted 15.3% +/- 13.1% of the cancer cells, and the average number of
      macrophages was 7.8% +/- 6.3%; neither correlated with FDG uptake. CONCLUSION: In
      this population of patients with NSCLC, Glut-1 is the major glucose transporter
      expressed. Both FDG uptake and Glut-1 expression appear to be associated with
      tumor size. No association was found between FDG uptake and either macrophage or
      proliferative cell populations.

PMID- 10210214
TI  - Feasibility of fluorodeoxyglucose dual-head gamma camera coincidence imaging in
      the evaluation of lung cancer: comparison with FDG PET.
AB  - The purpose of this study was to elucidate the feasibility of fluorodeoxyglucose
      gamma camera coincidence imaging (FDG GCI) in the evaluation of lung cancer in
      comparison with FDG PET. METHODS: Twenty-three patients with recently diagnosed
      lung cancer were examined with both FDG PET and FDG GCI on the same day.
      Pulmonary lesions were analyzed visually and semiquantitatively using the ratio
      of lesion-to-background counts (L/B ratio). The L/B ratio of FDG PET without
      attenuation correction (AC) was also calculated and compared. Nodal stations were
      only visually analyzed. RESULTS: FDG GCI and FDG PET could detect 22 and 23,
      respectively, of 23 pulmonary lesions by visual analysis (95.7% versus 100%). The
      L/B ratio of FDG GCI was 4.26 +/- 2.55, and significantly lower than that of FDG
      PET (9.29 +/- 4.95; P < 0.01). The L/B ratio of FDG PET was significantly higher
      with AC than that without AC (9.29 +/- 4.95 vs. 6.66 +/- 4.65; P < 0.01). When
      the L/B ratio threshold was set at 5.0 for FDG PET and 2.7 for FDG GCI, their
      sensitivity was 87.0% and 73.9%, respectively. Of the 3 and 6 patients with false
      negative results on semiquantitative analysis, the lesions in 3 patients on FDG
      PET and 4 patients on FDG GCI were less than or equal to 2.0 cm in greatest
      diameter, respectively. In the assessment of mediastinal involvement, FDG PET was
      77.8% sensitive, 78.6% specific and 78.3% accurate, whereas FDG GCI was 77.8%
      sensitive, 92.9% specific and 87.0% accurate. In the hilar regions, FDG PET was
      100% sensitive, 84.2% specific and 87.0% accurate, whereas FDG GCI was 75.0%
      sensitive, 89.5% specific and 87.0% accurate. CONCLUSION: In this study, FDG GCI
      yielded results comparable to FDG PET on visual analysis to detect pulmonary
      lesions and lymph node metastases. However, the lesion-to-background contrasts of
      pulmonary lesions and nodal involvement were lower in FDG GCI than in FDG PET.
      Comparison between the L/B ratio of FDG PET with and without AC indicated that,
      with AC, FDG GCI would be closer to FDG PET in the evaluation of lung cancer.

PMID- 10210215
TI  - Assessment of pulmonary lesions with 18F-fluorodeoxyglucose positron imaging
      using coincidence mode gamma cameras.
AB  - Accurate assessment of lung carcinoma remains a significant clinical problem,
      often leading to surgical procedures without curative potential. PET with 18F
      fluorodeoxyglucose (FDG) has shown promise in differentiating benign from
      malignant lesions and in staging the extent of disease, resulting in improved
      treatment at a significant cost savings. This multicenter prospective study used
      dual-detector coincidence imaging with FDG to categorize pulmonary lesions as
      benign or malignant. The goal of this study was to determine the sensitivity and
      specificity of dual-detector coincidence imaging of FDG in patients with
      pulmonary lesions who were scheduled to have a diagnostic procedure for
      histopathologic confirmation. METHODS: A total of 96 patients with pulmonary
      lesions with a lesion size ranging from 1 to 7 cm with a mean of 3.44 cm based on
      their chest radiograph or CT scan were studied using FDG scans with a dual
      detector coincidence detection system. An additional 24 patients were entered as
      control subjects. The studies of 120 subjects were interpreted in random order by
      three physicians experienced in the use of FDG in patients with lung cancer.
      Surgical pathology was used as the standard for identifying malignant lesions.
      RESULTS: There was 94% agreement between the readers in the independent
      interpretation of the FDG studies. In the 96 patients with pulmonary lesions, FDG
      studies were 97% sensitive and 80% specific in identifying proven malignant
      lesions. CONCLUSION: The results of this prospective study provide evidence that
      dual-detector coincidence imaging with FDG provides an accurate, sensitive and
      specific means of diagnosing malignancy in patients with pulmonary lesions.

PMID- 10210216
TI  - 99mTc technegas ventilation and perfusion lung scintigraphy for the diagnosis of
      pulmonary embolus.
AB  - Lung scintigraphy is used widely for diagnosis of pulmonary embolus (PE).
      Technegas ventilation imaging has many advantages over other methods, but little
      outcome data exists on this technique. The aims of this study were to better
      define the role of lung scintigraphy in the management of patients with suspected
      PE and to evaluate technegas ventilation imaging by following patient outcomes.
      METHODS: A group of 717 out of 834 consecutive patients, referred to a university
      teaching hospital for lung scintigraphy to confirm or refute the diagnosis of PE,
      was followed for 18-30 mo to determine clinical outcome. The follow-up endpoints
      were death as a result of PE, death as a result of hemorrhage after treatment for
      PE, uncomplicated survival, survival with subsequent PE, nonfatal hemorrhage
      after treatment for PE and recurrence of PE in treated patients. Ventilation
      imaging was performed using technegas, and perfusion imaging was performed using
      intravenous 99mTc macroaggregated albumin. The modified PIOPED (Prospective
      Investigation of Pulmonary Embolism Diagnosis) diagnostic criterion was used for
      interpretation of lung scintigraphy. RESULTS: Diagnostic results included 3.5%
      normal studies, 67.4% assessed as low probability for PE, 10% as moderate
      probability for PE and 19.1% as high probability for PE. A total of 231 patents
      received therapy with heparin, followed by warfarin, including those receiving
      anticoagulation therapy for other conditions. Ninety-six percent of patients with
      normal and low probability studies (n = 508) had good outcomes, 6 patients died
      as a result of PE and 12 subsequently developed PE. The odds ratio for death by
      PE in this group was 0.2. Of the 72 moderate probability studies, 39 patients
      were untreated. In this group there was 1 death due to PE, and PE subsequently
      developed in 2 patients. None of the remaining 33 treated patients died, but 4
      patients experienced bleeding complications. The odds ratio for death by PE in
      the moderate probability group was 0.7. In those patients with high-probability
      studies, there were 8 deaths by PE, 6 deaths by hemorrhage, 11 nonfatal
      hemorrhages and 7 patients who experienced recurrences of PE. The odds ratios in
      this group were 6 and 10 for death by PE, or death by PE and the treatment of PE,
      respectively. CONCLUSION: The use of the modified PIOPED diagnostic
      classification is valid for technegas lung scintigraphy. Using technegas,
      normal/low-probability and high-probability results are highly predictive of
      respective outcomes. Technegas lung scintigraphy reduces the number of
      indeterminate studies.

PMID- 10210217
TI  - Bone pain palliation with 85Sr therapy.
AB  - The aim of this retrospective study was to evaluate the efficacy of 85Sr in the
      palliation of metastatic bone pain. 85Sr decays by electron capture with a gamma
      emission of 514 keV and associated x-ray emissions of 10-15 keV; physical half
      life is 64 d. METHODS: Between 1977 and 1992, 119 doses of 85Sr chloride (mean
      activity 335 MBq [9 mCi]) were intravenously administered to 108 patients with
      hyperalgic generalized bone metastases from prostatic carcinoma (52 patients),
      breast carcinoma (41) or other cancers (15). Pain, performance status, blood and
      urinary excretion values were investigated during follow-up, and survival time
      was recorded. Strontium bone scans were obtained up to 8 wk after injection to
      document isotope biodistribution and to estimate absorbed doses. RESULTS: At 12
      wk, 72.2% of patients showed significant benefit from treatment, i.e., enhanced
      quality of life and pain relief; 49.1% became free of pain. These beneficial
      effects lasted from 1 to 36 mo (mean 4.3 mo). The best symptomatic improvement
      was seen in patients treated at an early stage of metastatic skeletal disease and
      in prostate cancer patients. No evidence of a significant dose-response
      relationship was found in the data analysis. The mean absorbed dose ratio of
      metastases to marrow was estimated at 8.2. We found no evidence that
      hematological toxicity was a major problem; however, all patients experienced a
      reduction in blood counts, especially in platelets. CONCLUSION: Systemic
      radionuclide therapy using 85Sr is a feasible, effective and well-tolerated
      palliative treatment in patients with refractory bone pain. We attained at least
      the same response rate as that reported with bone-seeking beta-emitting
      radionuclides such as 89Sr. The patients who benefited the most from 85Sr
      treatment were in an early stage of metastatic disease or had prostate cancer.
      Our clinical findings could not be linked to either the total injected activity
      of 85Sr or the estimated absorbed dose delivered to metastases.

PMID- 10210218
TI  - Oncological applications of FDG PET imaging: brain tumors, colorectal cancer,
      lymphoma and melanoma.
AB  - This article will focus primarily on body oncology diagnosis, staging and therapy
      monitoring using fluorodeoxyglucose (FDG) PET imaging. Common pitfalls and
      artifacts in body FDG imaging will be covered. Examples of diagnosis, staging and
      therapy monitoring of brain tumor, colorectal cancer, lymphoma and melanoma will
      be given. Importance of correlation with anatomic imaging and practical use of
      FDG imaging in patient management will be stressed.

PMID- 10210219
TI  - Bone SPECT of the spine: a comparison of attenuation correction techniques.
AB  - Image artifacts from variable self-attenuation are recognized as major sources of
      diagnostic uncertainty in SPECT. For myocardial perfusion studies, an attenuation
      map is often obtained from a separate transmission study. However, for many
      applications such as bone SPECT, it has been believed to be unnecessary to obtain
      a transmission study to correct for the effects of attenuation. We have had
      significant success in clinical management of lower spine pain using bone SPECT.
      This success has led us to consider SPECT for the management of cervical spine
      pain. Cervical spine reconstructions without attenuation correction are difficult
      to interpret, because the high attenuation in the mandible and skull tends to
      decrease estimates of activity of the upper cervical spine, and the lower
      cervical/upper thoracic vertebrae are obscured by the shoulders. We present a
      technique that uses downscatter to provide attenuation correction for these
      acquisitions and compare it with other recognized attenuation correction
      techniques. METHODS: An emission study is acquired using two windows: one for
      obtaining the photopeak data and another for obtaining the downscattered photons.
      A body outline is estimated from these datasets using a projection data
      thresholding method. From this outline, a uniform attenuation map is created
      using attenuation coefficients appropriate for 99mTc in water (0.154 cm(-1)).
      These maps are used in SPECT reconstruction using ordered-subset expectation
      maximization (OSEM). This method is compared with (a) no attenuation correction
      (NC), (b) conventional Chang attenuation correction based on the interactive
      determination of the body outline from the 99mTc emission photopeak data
      (ChangAC) and (c) OSEM correction using attenuation maps estimated with a line
      source and fanbeam collimators (transAC). RESULTS: Patient studies using
      scatterAC demonstrated a significant improvement in the uniformity of estimated
      cervical spine uptake in normal patients, compared with either NC or ChangAC.
      Results using scatterAC were similar to those of transAC. We also observed
      significant improvement in uniformity using scatterAC in SPECT of the lower back
      in obese patients, as well as the relative limitations of scatterAC versus
      nonuniform, transmission-based attenuation correction. CONCLUSION: Comparisons
      with reconstructions using transmission data for estimating attenuation
      demonstrate that reasonable quantitative accuracy can be obtained in SPECT of the
      cervical spine using this simple attenuation estimate. Both scatterAC and transAC
      appear to provide consistent and expected uniform spine uptake in the cervical
      spines of normal patients.

PMID- 10210220
TI  - Kinetic analysis of 2-[11C]thymidine PET imaging studies: validation studies.
AB  - 2-[11C]thymidine has been tested as a PET tracer of cellular proliferation. We
      have previously described a model of thymidine and labeled metabolite kinetics
      for use in quantifying the flux of thymidine into DNA as a measure of tumor
      proliferation. We describe here the results of studies to validate some of the
      model's assumptions and to test the model's ability to predict the time course of
      tracer incorporation into DNA in tumors. METHODS: Three sets of studies were
      conducted: (a) The uptake of tracers in proliferative tissues of normal mice was
      measured early after injection to assess the relative delivery of thymidine and
      metabolites of thymidine catabolism (thymine and CO2) and calculate relative
      blood-tissue transfer rates (relative K1s). (b) By using sequential injections of
      [11C]thymidine and [11C]thymine in normal human volunteers, the kinetics of the
      first labeled metabolite were measured to determine whether it was trapped in
      proliferating tissue such as the bone marrow. (c) In a multitumor rat model, 2
      [14C]thymidine injection, tumor sampling and quantitative DNA extraction were
      performed to measure the time course of label uptake into DNA for comparison with
      model predictions. RESULTS: Studies in mice showed consistent relative delivery
      of thymidine and metabolites in somatic tissue but, as expected, showed reduced
      delivery of thymidine and thymine in the normal brain compared to CO2. Thymine
      studies in volunteers showed only minimal trapping of label in bone marrow in
      comparison to thymidine. This quantity of trapping could be explained by a small
      amount of fixation of labeled CO2 in tissue, a process that is included as part
      of the model. Uptake experiments in rats showed early incorporation of label into
      DNA, and the model was able to fit the time course of uptake. CONCLUSION: These
      initial studies support the assumptions of the compartmental model and
      demonstrate its ability to quantify thymidine flux into DNA by using 2
      [11C]thymidine and PET. Results suggest that further work will be necessary to
      investigate the effects of tumor heterogeneity and to compare PET measures of
      tumor proliferation to in vitro measures of proliferation and to clinical tumor
      behavior in patients undergoing therapy.

PMID- 10210221
TI  - Radiation dosimetry of a 99mTc-labeled IgM murine antibody to CD15 antigens on
      human granulocytes.
AB  - 99mTc-labeled anti-stage specific embryonic antigen-1 (anti-SSEA-1) is an
      injectable IgM antibody derived from mice. It binds to CD15 antigens on some
      granulocytic subpopulations of human white blood cells in vivo after systemic
      administration. The purpose of this study was to measure biodistribution of 99mTc
      labeled anti-SSEA-1 and perform radiation dosimetry in 10 healthy human
      volunteers. METHODS: Transmission scans and whole-body images were acquired
      sequentially on a dual-head camera for 32 h after the intravenous administration
      of about 370 MBq (10.0 mCi) of the radiopharmaceutical. Renal excretion fractions
      were measured from 10 to 14 discrete urine specimens voided over 27.9 +/- 2.0 h.
      Multiexponential functions were fit iteratively to the time-activity curves for
      17 regions of interest using a nonlinear least squares regression algorithm. The
      curves were integrated numerically to yield source organ residence times. Gender
      specific radiation doses were then estimated individually for each subject, using
      the MIRD technique, before any results were averaged. RESULTS: Quantification
      showed that the kidneys excreted 39.5% +/- 6.5% of the administered dose during
      the first 24 h after administration. Image analysis showed that 10%-14% of the
      radioactivity went to the spleen, while more than 40% went to the liver.
      Residence times were longest in the liver (3.37 h), followed by the bone marrow
      (1.09 h), kidneys (0.84 h) and the spleen (0.65 h). The dose-limiting organ in
      both men and women was the spleen, which received an average of 0.062 mGy/MBq
      (0.23 rad/mCi, range 0.08-0.30 rad/mCi), followed by the kidneys (0.051 mGy/MBq),
      liver (0.048 mGy/MBq) and urinary bladder (0.032 mGy/MBq). The effective dose
      equivalent was 0.018 mSv/MBq (0.068 rem/mCi). CONCLUSION: The findings suggest
      that the radiation dosimetry profile for this new infection imaging agent is
      highly favorable.

PMID- 10210222
TI  - Dosimetry of 131I-labeled 81C6 monoclonal antibody administered into surgically
      created resection cavities in patients with malignant brain tumors.
AB  - The objective of this study was to perform the dosimetry of 131I-labeled 81C6
      monoclonal antibody (MAb) in patients with recurrent malignant brain tumors,
      treated by direct injections of MAb into surgically created resection cavities
      (SCRCs). METHODS: Absorbed dose estimates were performed for nine patients.
      Dosimetry was performed retrospectively using probe counts (during patient
      isolation) and whole-body and SPECT images thereafter. Absorbed doses were
      calculated for the SCRC interface and for regions of interest (ROIs) 1 and 2 cm
      thick, measured from the margins of cavity interface. Also, mean absorbed doses
      were calculated for normal brain, liver, spleen, thyroid gland, stomach, bone
      marrow and whole body. The average residence time for the SCRC was 111 h (65
      200h). RESULTS: The average absorbed dose per unit injected activity (range) to
      the SCRC interface and ROIs 1 and 2 cm thick from the cavity interface were 31.9
      (7.8-84.2), 1.9 (0.7-3.6) and 1.0 (0.4-1.8) cGy/MBq, respectively. Average
      absorbed doses per unit administered activity to brain, liver, spleen, thyroid,
      stomach, bone marrow and whole body were 0.18, 0.03, 0.08, 0.05, 0.02, 0.02 and
      0.01 cGy/MBq, respectively. The high absorbed dose delivered to the SCRC
      interface may have produced an increase in cavity volume independent of tumor
      progression. CONCLUSION: At the maximum tolerated dose of 3700 MBq 131I-labeled
      81C6 MAb, the absorbed doses to the SCRC interface and ROIs of 1 and 2 cm
      thickness were estimated to be 1180, 71 and 39 Gy, respectively. The estimated
      average absorbed dose to the brain was 6.5 Gy. There was no neurological toxicity
      and minimal hematologic toxicity at this maximum tolerated administration level.

PMID- 10210223
TI  - 186Re-etidronate in breast cancer patients with metastatic bone pain.
AB  - The aim of this study was to evaluate the efficacy of 186Re-1,1-hydroxyethylidene
      diphosphonate (etidronate) in breast cancer patients with painful bone
      metastases. METHODS: Thirty patients with advanced breast cancer who had
      metastatic bone pain were treated with 186Re-etidronate using different dosages
      in a noncomparative, open-label study. Twenty-four patients were evaluated for
      efficacy (6 patients had incomplete datasets). Dosages varied from 1295 to 2960
      MBq (35 to 80 mCi). Efficacy was evaluated according to the multidimensional pain
      model using a paper-and-pencil diary. The diary was kept twice daily for 8-10 wk
      (2 wk before through 6-8 wk after 186Re-etidronate treatment). Response was
      determined with a strict criteria, in which pain intensity (PI), medication index
      (MI) and daily activities (DA) were core determinants. Response was defined as:
      (a) Reduced PI > or = 5% while MI and DA were at least constant; or (b) Reduced
      PI <25% in combination with improvement of MI or DA > or = 25%, without worsening
      of either factor. Duration of response should always exceed a minimum of 2 wk.
      RESULTS: Fifty-eight percent (n = 14) of all patients reported a response. The
      maximum follow-up period was 8 wk. Duration of response ranged from 2 to 8 wk
      (mean 4 wk). Patients (14/24) not only experienced considerable pain reduction,
      but in 12 patients this was also accompanied by noteworthy reduction in MI (> or
      = 25%). No clear dose-response relationship was found. CONCLUSION: With strict
      pain assessment criteria, 186Re-etidronate showed a response of 58% in the
      palliative treatment of metastatic bone pain originating from breast cancer.

PMID- 10210224
TI  - Quantitative 99mTc-DMSA uptake in experimental pyelonephritis.
AB  - Quantitative 99mTc-dimercaptosuccinic acid (DMSA) renal uptake was studied in
      unilateral reflux-related pyelonephritis in pigs. The changes to absolute % dose
      uptake and differential uptake occurring with induction and after treatment of
      pyelonephritis were correlated with the DMSA images and renal pathology. METHODS:
      Quantitative uptake in 53 young pigs was obtained from planar images acquired 6 h
      after injecting the dose. Baseline studies were made (Q1), and studies were made
      again after urinary infection was established (Q2), when 8 pigs had normal (no
      defect) renal images (group A), 23 had photon-deficient (reversible) focal
      defects (group B) and 22 had photon absent (irreversible) focal defects (group
      C). Q3 studies were made in 21 animals from groups B and C after 3-wk
      antimicrobial treatment. RESULTS: At Q2 the affected kidney differential uptake
      was unchanged for group A and reduced for groups B and C (respective mean changes
      -1.7%, P < 0.01; and -5.5%, P < 0.01). The absolute % dose uptake was unchanged
      in pyelonephritic kidneys, but increased in the contralateral nondiseased kidneys
      in groups B and C (respective mean increases +1.4%, P < 0.05; and +5.4%, P <
      0.01), while remaining unchanged for group A. In group C, global renal
      accumulation was actually increased above the Q1 values. After treatment (Q3) the
      reduced pyelonephritic kidney differential uptake persisted in groups B and C. In
      group C, however, the increased absolute % dose uptake by the contralateral
      kidney was less marked and not significantly different from Q1 values in this
      small group. CONCLUSION: Induction of unilateral pyelonephritis produced a small
      reduction in diseased kidney differential uptake that was greatest in the group
      with irreversible imaging defects. The method did not discriminate individuals
      with reversible and irreversible imaging defects. The decrease in pyelonephritic
      kidney differential uptake resulted from increased DMSA accumulation (absolute %
      dose uptake) by the nondiseased contralateral kidney, while that in
      pyelonephritic kidneys remained unchanged. After treatment, the reduced
      pyelonephritic kidney differential uptake persisted, but the elevated global DMSA
      accumulation seen for group C (with irreversible imaging defects) was not
      sustained and was variable.

PMID- 10210225
TI  - Left ventricular function and perfusion from gated SPECT perfusion images: an
      integrated method.
AB  - A new technique for computing left ventricular function, including left
      ventricular volumes, mass and ejection fraction, has been developed. This method
      is a logical extension of the results of a standard perfusion quantification
      technique; thus, it allows integration of perfusion and functional information.
      METHODS: Anatomically based models of the endocardial and epicardial surfaces are
      generated using the myocardial samples for which perfusion values are quantified,
      for all frames in the cardiac cycle. With these surface points, left ventricular
      chamber volume and myocardial volume can be computed. A computer simulation was
      used to determine the sensitivity of the approach to the assumptions of the
      model. Validation of volume, mass and ejection fraction was performed with
      correlative MR studies, and ejection fraction and left ventricular volumes were
      further investigated using correlative first-pass studies. RESULTS: Automated
      processing was successful in 96% of the cases analyzed. End diastolic volume, end
      systolic volume, left ventricular mass and left ventricular ejection fraction
      correlated with MRI with r = 0.97, 0.99, 0.87, and 0.85, respectively. Ejection
      fraction from tomography correlated with first-pass values with r = 0.82, and end
      diastolic and end systolic volumes from tomography correlated with first-pass
      values with r = 0.85 and r = 0.91, respectively. CONCLUSION: The new integrated
      approach is accurate and robust for computing both perfusion and function from
      perfusion tomograms.

PMID- 10210226
TI  - Simultaneous SPECT studies of pre- and postsynaptic dopamine binding sites in
      baboons.
AB  - The central nervous system dopamine transporters (DATs) and dopamine D2/D3
      receptors are implicated in a variety of neurological disorders. Both sites are
      also targets for drug treatment. With the successful development of [99mTc]TRODAT
      1, single-isotope imaging studies using this ligand for DAT imaging can be
      complemented by additional use of 123I-labeled D2/D3 receptor ligand co-injected
      to assess both pre- and postsynaptic sites of the dopaminergic system
      simultaneously. METHODS: Twelve SPECT scans of the brain were obtained in two
      baboons after intravenous administration of 740 MBq (20 mCi) [99mTc]-TRODAT-1
      (technetium, [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2
      yl]methyl ](2-mercaptoethyl) amino]ethyl]-amino]ethanethiolato (3-)]- oxo-[1R
      (exo-exo)]) and 185 MBq (5 mCi) [123I]iodobenzamide or [123I]iodobenzofuran.
      SPECT data were acquired by a triple-head gamma camera equipped with ultra-high
      resolution fanbeam collimators (scan duration = 210 min). Two sets of SPECT data
      were obtained using energy windows of 15% centered on 140 keV for 99mTc and 10%
      asymmetric with a lower bound at 159 keV for 123I. After coregistration with MRI,
      region-of-interest analysis was performed using predefined templates from
      coregistered MRI. In blocking studies, baboons were pretreated with N-methyl
      2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane (CFT, 14 mg) or raclopride (14
      mg) to block DAT or D2/D3 binding site, respectively. RESULTS: Image quality of
      dual-isotope studies was similar to that obtained from single-isotope studies.
      When one site was blocked with CFT or raclopride, the binding of the respective
      ligand to the other site was not affected. CONCLUSION: This is the first example
      that clearly demonstrates the feasibility of simultaneous imaging of both pre-
      and postsynaptic sites of the dopaminergic system in baboons with dual-isotope
      SPECT studies. With or without corrections for cross-contamination of 123I into
      the 99mTc window, striatum-to-cerebellum ratios (target-to-nontarget) of dual
      isotope experiments did not differ significantly from single-isotope experiments.
      This method may be a valuable and cost-effective tool for gaining comprehensive
      information about the dopaminergic system in one SPECT imaging session.

PMID- 10210227
TI  - Combination 186Re-HEDP and cisplatin supra-additive treatment effects in prostate
      cancer cells.
AB  - Radionuclide therapy has proven to be an efficacious palliative treatment for
      metastatic prostate cancer. Its potential therapeutic possibilities may be
      substantially increased by combining it with effective radiosensitizing drugs.
      METHODS: This study explores the radiosensitizing properties of cisplatin when
      combined with 186Re-labeled hydroxyethylidene diphosphonate (HEDP) in the
      treatment of R3327-MATLyLu prostate cancer cells in vitro. A concomitant
      incubation during 4 d, combining various concentrations of cisplatin (0, 0.42,
      0.83 and 1.67 micromol/L) and 186Re-HEDP (0, 1.84 and 3.69 MBq/mL [0, 50 and 100
      microCi/mL, respectively]) was followed by the determination of the cell numbers
      surviving and the replating of these cells in semisolid agar. RESULTS: The
      surviving fraction of clonogenic tumor cells after combination treatment clearly
      showed synergism when analyzed by a panel of three different published analytical
      methods. In addition, analysis of variance demonstrated a significant interaction
      between radionuclide therapy and cisplatin-based chemotherapy (P < 0.001).
      Treatment with 186Re-HEDP and cisplatin by sequential incubation yielded similar,
      but never superior results. CONCLUSION: It is concluded that radionuclide therapy
      in combination with cisplatin is able, in principle, to improve therapeutic
      success rate in metastatic prostate cancer in a more than additive way.

PMID- 10210228
TI  - Comparative 99mTc-sestamibi and 3H-daunomycin uptake in human carcinoma cells:
      relation to the MDR phenotype and effects of reversing agents.
AB  - Because 99mTc-sestamibi (MIBI) appears to be a potent candidate for multidrug
      resistance (MDR) evaluation in tumors, its cellular uptake should be similar to
      that of 3H-daunomycin in a variety of conditions of expression and inhibition of
      MDR activity. METHODS: We used a human rhinopharyngeal carcinoma cell line (KB-3
      1) and its MDR variant (KB-A1). Cells were incubated 2 h with 99mTc-MIBI and 3H
      daunomycin under control conditions or in the presence of a reversing agent such
      as verapamil (10 pmol/L), PSC833 (1 micromol/L) or S9788 (5 micromol/L). RESULTS:
      Relative to the KB-3-1-sensitive cells, accumulations of 99mTc-MIBI and 3H
      daunomycin were reduced to 31% +/- 5% and 36% +/- 11% (P < 0.001 for both) in KB
      A1-resistant cells. In sensitive cells, accumulation of both agents was increased
      by verapamil and PSC833 (range 115%-140%; P < 0.05) but not by S9788. In KB-A1
      cells, only S9788 significantly increased the cellular uptake of 99mTc-MIBI (138%
      +/- 25%; P < 0.01), whereas the intracellular uptake of 3H-daunomycin was
      markedly increased with the three reversing agents (up to 311% +/- 37% with
      S9788; P < 0.001). With this last treatment, uptake of 3H-daunomycin in KB-A1
      cells nearly returned to its basal level in sensitive cells. CONCLUSION: 99mTc
      MIBI monitors the MDR phenotype of tumor cells effectively but responds to
      reversing agents differently than 3H-daunomycin.

PMID- 10210229
TI  - Dual-isotope SPECT using simultaneous acquisition of 99mTc and 123I
      radioisotopes: a double-injection technique for peri-ictal functional
      neuroimaging.
AB  - The acquisition of multiple radiotracer studies at different time points during a
      neurological event permits the study of different functional activation states in
      humans. Peri-ictal SPECT is a promising technique for localizing the
      epileptogenic zone and would be enhanced by the ability to acquire sequentially
      coregistered ictal and postictal SPECT images of a single seizure. This study was
      designed to develop and validate an accurate method for the simultaneous
      acquisition of 99mTc and 123I SPECT images of the brain. METHODS: A
      multicompartment, transaxial Hoffman brain-slice phantom was filled with 99mTc,
      123I or a 3:1 mixture of the two isotopes. Planar and SPECT images were acquired
      by a dual-head gamma camera system equipped with parallel and fanbeam
      collimators, respectively. Thirty-two energy windows (2 keV width) were acquired
      over the energy range 120-184 keV. From the planar data, the signal-to-noise
      characteristics and crosstalk were measured for each energy window and used to
      devise an energy window acquisition strategy that was then applied to the SPECT
      data. Three summed energy windows were created: a primary 99mTc image (130-146
      keV), a primary 123I image (152-168 keV) and a secondary 99mTc crosstalk image
      (134-140 keV). A fraction (0.041) of the 99mTc crosstalk image was subtracted
      from the 123I image. No crosstalk correction was performed on the primary 99mTc
      image. RESULTS: (a) Planar images: results showed 1.3% crosstalk in the 123I
      image compared with 19.7% for a 10% asymmetric energy window alone. 123I
      crosstalk into the 99mTc window was 2.79% and was relatively constant with
      changes in the location of the 99mTc energy window. (b) Tomographic images:
      results showed 1.51% 99mTc crosstalk in the 123I image compared with 12.44% for
      the uncorrected image and 3.70% 123I crosstalk in the 99mTc image. CONCLUSION: An
      effective technique for the simultaneous acquisition of 99mTc and 123I
      radiotracer distributions in the brain has been developed and validated in a
      phantom model and should have clinical application in peri-ictal functional
      activation studies of the brain.

PMID- 10210230
TI  - Intratumoral distribution of radiolabeled antibody and radioimmunotherapy in
      experimental liver metastases model of nude mouse.
AB  - The biodistribution and intratumoral distribution of radiolabeled
      anticarcinoembryonic antigen (CEA) monoclonal antibody in experimental liver
      metastases and the therapeutic effect of 131I-labeled anti-CEA antibody on the
      metastases were studied. METHODS: Three weeks after an intrasplenic injection of
      human colon cancer cells, mice received an intravenous injection of 125I- or
      111In-labeled anti-CEA antibody F33-104. The biodistribution and tumor
      penetration of radiolabeled antibody were examined by using quantitative
      autoradiography. To evaluate the therapeutic effect, 5.55, 9.25 or 11.1 MBq (150,
      250 or 300 microCi) 131I-labeled F33-104 were injected into groups of mice that
      had micrometastases smaller than 1 mm. Control groups were injected with
      phosphate-buffered saline or 131I-labeled control antibody. Mice were killed 3 wk
      later to determine the size of liver metastases. RESULTS: 1251-labeled F33-104
      showed a high accumulation in the liver metastases (percentage of injected dose
      per gram of metastases [%ID/g] >24%, metastasis-to-liver ratio >9.8, metastasis
      to-blood ratio >2.1); however, its accumulation was heterogeneous or peripheral
      in the nodules more than 1 mm in diameter. When the antibody dose was increased,
      antibody penetration was improved, but tumor uptake of radioactivity and
      specificity ratios decreased. In mice with large metastases, radioactivity in the
      normal tissue was lower than that in mice with small metastases, resulting in
      higher metastasis-to-background ratios. 111In-labeled antibody showed even higher
      tumor uptake than 125I-labeled antibody (>51 %ID/g). Metastases formation was
      suppressed in a dose-dependent manner by 131I-labeled F33-104 injection (5 of 8
      mice had no macroscopic tumor after an injection of 5.55 MBq (150 microCi), and
      all mice had no visible metastasis after an injection of 9.25 or 11.1 MBq [250 or
      300 microCi]), whereas tumor progression was seen in the control groups.
      CONCLUSION: Liver metastases had easy accessibility to the antibody.
      Micrometastases of less than 0.5 mm in diameter showed homogeneous intratumoral
      distribution of injected antibody and were successfully treated with 131I-labeled
      antibody. Very high uptake and satisfactory metastasis-to-liver ratios with 111In
      labeled antibody suggest that the use of a radiometal with high beta-energy, such
      as 90Y or 188Re, is preferable for the successful radioimmunotherapy of
      metastases larger than 1 mm.

PMID- 10210231
TI  - Antisense and nuclear medicine.
AB  - Despite many uncertainties concerning mechanism, synthetic single-strand
      antisense deoxyribonucleic acids (DNAs) are now in clinical trials for the
      chemotherapy of viral infections such as human immunodeficiency virus (HIV) and
      human papilloma virus; several cancers, including follicular lymphoma and acute
      myelogenous leukemia; inflammatory processes such as Crohn's disease and
      rheumatoid arthritis and in allergic disorders. There are approximately 10
      trials, and early results are generally encouraging. Therefore, the expectation
      is that antisense DNAs will be important to future chemotherapy. The question
      considered here is whether antisense DNAs will also be important to future
      nuclear medicine imaging. While efforts toward developing antisense imaging are
      comparatively nonexistent thus far, investigations into the mechanisms of
      cellular transport and localization and the development of a second generation of
      antisense DNAs have occurred largely within the antisense chemotherapy industry.
      Fortunately, many of the properties of DNA for antisense imaging, such as high in
      vivo stability and adequate cell membrane transport, are the same as those for
      antisense chemotherapy. Unfortunately, interests diverge in the case of several
      other key properties. For example, rapid localization and clearance kinetics of
      the radiolabel and prolonged retention in the target are requirements unique to
      nuclear medicine. No doubt the development of antisense imaging will continue to
      benefit from improvements in the antisense chemotherapy industry. However, a
      considerable effort will be required to optimize this approach for imaging (and
      radiotherapy). The potential of specifically targeting virtually any disease or
      normal tissue should make this effort worthwhile.

PMID- 10210232
TI  - MIRD Pamphlet No. 14 revised: A dynamic urinary bladder model for radiation dose
      calculations. Task Group of the MIRD Committee, Society of Nuclear Medicine.
AB  - The constant-volume urinary bladder model in the standard MIRD Pamphlet No. 5
      (Revised) phantom has recognized limitations. Various investigators have
      developed detailed models incorporating more physiologically realistic features,
      such as expanding bladder contents and residual volume, and variable urinary
      input rate, initial volume and first void time. We have reviewed these published
      models and have developed a new model for calculation of radiation absorbed dose
      to the urinary bladder wall incorporating these aspects. METHODS: The model
      consists of a spherical source with variable volume to simulate the bladder
      contents and a wall represented by a spherical shell of constant volume. The wall
      thickness varies as the source expands or contracts. The model provides for
      variable urine entry rate (three different hydration states), initial bladder
      contents volume, residual volume and first void time. The voiding schedule
      includes an extended nighttime gap during which the urine entry rate is reduced
      to one-half the daytime rate. RESULTS: Radiation-absorbed dose estimates have
      been calculated for the bladder wall surface (including photon and electron
      components) and at several depths in the wall (electron component) for 2-18F
      fluoro-2-deoxy-D-glucose, 99mTc-diethylenetriaminepentaacetic acid (DTPA), 99mTc
      HEDP, 99mTc-pertechnetate, 99mTc-red blood cells (RBCs), 99mTc-glucoheptonate,
      99mTc-mercaptoacetyltriglicine chelator (MAG3), 99mTc-methylene diphosphonate
      (MDP), 99mTc-hexamethylpropylene amine oxime (HMPAO), 99mTc-human serum albumin
      (HSA), 99mTc-MIBI (rest and stress), 123I-/124I-/131I-OIH, 123I/131I-NaI, 125I
      iothalamate, 111In-DTPA and 89Sr-SrCl. CONCLUSION: The new model tends to give a
      higher radiation absorbed dose to the bladder wall surface than the previous
      models. Large initial bladder volumes and higher rates of urine flow into the
      bladder result in lower bladder wall dose. The optimal first voiding time is from
      40 min to 3 hr postadministration, depending on radiopharmaceutical. The data as
      presented in tabular and graphic form for each compound provide guidance for
      establishing radiation absorbed dose reduction protocols.

PMID- 10210233
TI  - Chronic comorbidity and outcomes of hospital care: length of stay, mortality, and
      readmission at 30 and 365 days.
AB  - This article evaluates the behavior of an adaptation of the Charlson Index (CHI)
      applied to administrative databases to measure the relationship between chronic
      comorbidity and the hospital care outcomes of length of stay (LOS), in-hospital
      mortality, and emergency readmissions at 30 and 365 days. These outcomes were
      analyzed in 106,673 hospitalization episodes whose records are registered in a
      minimum basic data set maintained by the public health authorities of the
      community of Valencia, Spain. The highest comorbidity measured by the CHI was
      associated with greater LOS and in-hospital mortality and increased readmission
      at 30 and 365 days. The rate of readmissions at 1 year dropped, however, in the
      group with the greatest comorbidity, probably owing to an increase in mortality
      after hospitalization. While comorbidity does appear to increase the risk of
      adverse outcomes in general and mortality and readmission specifically, the
      second outcome is only possible if the first has not occurred. For this reason,
      information and selection biases derived from administrative databases, or from
      the CHI itself, should be taken into account when using and interpreting the
      index.

PMID- 10210234
TI  - Functional status of elderly home care users: do subjects, informal and
      professional caregivers agree?
AB  - Professional or informal proxy respondents are frequently used in surveys when
      physical or mental health may compromise the ability to participate or the
      quality of responses. Functional status (Katz activities of daily living [ADL],
      Lawton instrumental activities of daily living [IADL]) was assessed in a sample
      of 420 chronically dependent elderly receiving home care. Separate in-person
      interviews were conducted with subjects, main informal caregivers and
      professionals coordinating home care. We found substantial agreement (Kappa)
      particularly between subjects and informal caregivers in all ADL except
      continence and in all IADL except housekeeping. High levels of agreement were
      also found for cognitively impaired subjects (Mini-Mental State Examination <24).
      Disagreement was characterized by more frequent reports of dependence from
      informal and professional caregivers. Our data suggest that proxy responses by
      informal caregivers conform with answers provided by subjects but produce
      slightly higher estimates of dependence and that cognitively impaired elderly
      living in the community will provide accurate information on their functional
      status in most cases.

PMID- 10210235
TI  - Generic and specific measurement of health-related quality of life in a clinical
      trial of respiratory rehabilitation.
AB  - The purpose of this study was to compare the performance of measures of health
      related quality of life in a randomized controlled trial of respiratory
      rehabilitation versus conventional community care for patients with chronic
      airflow limitation. The study included 89 stable patients with moderate to severe
      chronic airflow limitation with measurement of health status at 12, 18, and 24
      weeks. Outcomes included two disease-specific (the Oxygen Cost Diagram and the
      Chronic Respiratory Questionnaire [CRQ]) measures, a generic health profile (the
      Sickness Impact Profile [SIP]), and two utility measures (the Standard Gamble and
      the Quality of Well-Being index [QWB]). Of the measures, only the four domains of
      the CRQ (dyspnea, fatigue, mastery, and emotional function) showed statistically
      significant differences (P < or = 0.05) between treatment and control groups.
      Correlation between change in the CRQ and change in other relevant measures,
      including the 6-minute walk test and global ratings of change in dyspnea,
      fatigue, and emotional function were generally weak to moderate (from 0.19 to
      0.51). All correlations between change in the QWB, SIP, and Standard Gamble and
      other measures were very weak or weak (up to 0.30). Correlation between change in
      the three generic measures were all very weak (<0.15). The results suggest that
      unless investigators include responsive and valid disease-specific measures of
      health-related quality of life in controlled trials in chronic diseases, they
      risk misleading conclusions about the effect of treatments on health status.

PMID- 10210236
TI  - How should importance and severity ratings be combined for item reduction in the
      development of health status instruments?
AB  - Patients' ratings of the severity and importance of items are often used to
      select items for health status instruments. The purpose of this study was to
      compare six different methods of combining severity-importance ratings. Two
      different patient groups separately rated the importance and severity of their
      complaints; (i) 76 patients with upper-extremity disorders rated 70 upper
      extremity-related questions; and (ii) 86 patients with hip arthrosis rated 22
      questions relating to their hip problem. The rank ordering of the items using the
      six different methods in the two populations were very similar (tau(bi) = 0.91
      and 0.87, respectively). Furthermore, the six methods when used to choose 30
      upper-extremity items shared 25 items in common and shared 9 (of 10) hip items in
      the second group. In conclusion, the results of item reduction were not affected
      by the method of creating importance-severity ratings.

PMID- 10210237
TI  - The use of automated data to identify complications and comorbidities of
      diabetes: a validation study.
AB  - We evaluated the accuracy of administrative data for identifying complications
      and comorbidities of diabetes using International Classification of Diseases, 9th
      edition, Clinical Modification and Current Procedural Terminology codes. The
      records of 471 randomly selected diabetic patients were reviewed for
      complications from January 1, 1993 to December 31, 1995; chart data served to
      validate automated data. The complications with the highest sensitivity
      determined by a diagnosis in the medical records identified within +/-60 days of
      the database date were myocardial infarction (95.2%); amputation (94.4%);
      ischemic heart disease (90.3%); stroke (91.2%); osteomyelitis (79.2%); and
      retinal detachment, vitreous hemorrhage, and vitrectomy (73.5%). With the
      exception of amputation (82.9%), positive predictive value was low when based on
      a diagnosis identified within +/-60 days of the database date but increased with
      relaxation of the time constraints to include confirmation of the condition at
      any time during 1993-1995: ulcers (88.5%); amputation (85.4%); and retinal
      detachment, vitreous hemorrhage and vitrectomy (79.8%). Automated data are useful
      for ascertaining potential cases of some diabetic complications but require
      confirmatory evidence when they are to be used for research purposes.

PMID- 10210238
TI  - Association of dialyzer reuse with hospitalization and survival rates among U.S.
      hemodialysis patients: do comorbidities matter?
AB  - The objective of this study was to determine whether the associations between
      reuse of hemodialyzers and higher rates of death and hospitalization persist
      after adjustment for comorbidity. This was a nonconcurrent cohort study of
      survival and hospitalization rates among 1491 U.S. chronic hemodialysis patients
      beginning treatment in 1986 and 1987. The impact of dialyzer reuse was compared
      across three survival models: an unadjusted model, a "base" model adjusted only
      for demographics and renal diagnosis, and an "augmented" model additionally
      adjusted for comorbidities. We found that reuse of dialyzers was associated with
      a similarly higher rate of death in analyses unadjusted for confounders (relative
      risk [RR] 1.25, 95% confidence interval [CI] 0.97-1.61), adjusted for
      demographics and renal diagnosis (RR 1.16, 95% CI 0.96-1.41), and analyses
      additionally adjusted for comorbidities (RR = 1.25, CI, 1.03, 1.52). Reusing
      dialyzers was also associated with a greater rate of hospitalization that was
      stable regardless of adjustment procedures. We conclude that higher rates of
      death and hospitalization associated with dialyzer reuse persist regardless of
      adjustment for demographic characteristics or baseline comorbidities. These
      findings amplify concerns that there exists elevated morbidity among hemodialysis
      patients treated in facilities that reuse hemodialyzers. Although the association
      we observed was not confounded by comorbidity, a cause-and-effect relationship
      between dialyzer reuse and morbidity could not be proved because of the inability
      to control for aspects of care other than dialyzer reuse.

PMID- 10210239
TI  - Accuracy of recall of occupational physical activity by questionnaire.
AB  - The validity of the Tecumseh Occupational Activity Questionnaire (TOQ) and a
      modified Seven Day Recall (SDR) was measured in 46 healthy women, ages 20-60
      years (mean +/- SD, 39.4 +/- 11.8). Occupational data were compared with direct
      (7-day occupational activity records and Caltrac accelerometer) and indirect
      (maximal oxygen uptake and percent body fat) measures of physical activity
      status. Physical activity survey and occupational record data were log
      transformed to normalize skewed distributions. Intraclass correlations ranged
      from r = 0.26 to 0.73 (P < 0.05) between similar activities on the TOQ and
      activity records for light intensity sitting, light-to-moderate intensity
      standing, and walking. Correlations between similar activities from the SDR and
      activity records ranged from r = 0.32 to 0.35 (P < 0.05) for light and moderate
      intensity activities. Correlations for total occupational activity between the
      surveys and activity records were r = 0.46 (P < 0.001) for the TOQ and r = 0.45
      (P < 0.01) for the SDR. A modest correlation (r = 0.34, P < 0.10) was observed
      between the Caltrac scores and TOQ moderate intensity standing. Only the TOQ
      light-to-moderate intensity standing was related to maximal oxygen uptake (r =
      0.32, P < 0.05). None of the measures were related to percent body fat (P >
      0.05). These results suggest that the TOQ and SDR both provide reasonably
      accurate measurements of light and moderate intensity occupational physical
      activity.

PMID- 10210240
TI  - Increasing physicians' awareness of the impact of statistics on research
      outcomes: comparative power of the t-test and and Wilcoxon Rank-Sum test in small
      samples applied research.
AB  - To effectively evaluate medical literature, practicing physicians and medical
      researchers must understand the impact of statistical tests on research outcomes.
      Applying inefficient statistics not only increases the need for resources, but
      more importantly increases the probability of committing a Type I or Type II
      error. The t-test is one of the most prevalent tests used in the medical field
      and is the uniformally most powerful unbiased test (UMPU) under normal curve
      theory. But does it maintain its UMPU properties when assumptions of normality
      are violated? A Monte Carlo investigation evaluates the comparative power of the
      independent samples t-test and its nonparametric counterpart, the Wilcoxon Rank
      Sum (WRS) test, to violations from population normality, using three commonly
      occurring distributions and small sample sizes. The t-test was more powerful
      under relatively symmetric distributions, although the magnitude of the
      differences was moderate. Under distributions with extreme skews, the WRS held
      large power advantages. When distributions consist of heavier tails or extreme
      skews, the WRS should be the test of choice. In turn, when population
      characteristics are unknown, the WRS is recommended, based on the magnitude of
      these power differences in extreme skews, and the modest variation in symmetric
      distributions.

PMID- 10210241
TI  - Validation of logistic regression models in small samples: application to
      calvarial lesions diagnosis.
AB  - We have used the leave-one-out (LOO) method and the area under the receiver
      operating characteristic (ROC) curve to validate logistic models with a sample of
      167 patients with calvarial lesions. Seven logistic regression models were
      developed from 12 clinical and radiological variables to predict the most common
      diagnoses separately. The LOO method was used to test the validity of the
      equations. The discriminant power of every model was assessed by means of the
      area under the ROC curve (Az). The model with the greatest discrimination ability
      for the whole data set was the osteoma equation (Az = 0.951). The discriminatory
      ability of the statistical models decreased significantly with the LOO procedure,
      having the malignancy model the highest value (Az = 0.931). The LOO method can
      obtain a high benefit from small samples in order to validate prediction rules.
      In studies with small samples, resampling techniques such as the LOO should be
      routinely used in predictive modeling. This method may improve the forecast of
      infrequent diseases, such as calvarial lesions.

PMID- 10210242
TI  - Fracture risk in the U.S. Medicare population.
AB  - Using data from the 5% U.S. Medicare sample, we estimated the actuarial (life
      table) risk that a person aged 65 will fracture the upper or lower limbs or the
      pelvis, by age 75, 80, 85, and 90, taking into account the chance of dying in the
      interval. The actuarial risk of a 65-year old white woman sustaining a fracture
      by age 90 is 16% for the hip, 9% for distal forearm, 5% for proximal humerus, and
      4% for ankle. Black women and white men have substantially lower risks, and the
      risks for black men are very low. Although hip fractures pose the single greatest
      risk, the risk of all other fractures combined is greater. White women have
      particularly high risks for all fractures, because of their longevity as well as
      their high fracture rates. It is important to adjust for the probability of dying
      when estimating risks in an elderly population.

PMID- 10210243
TI  - Modeling of high-cost patient distribution within renal failure diagnosis related
      group.
AB  - Modeling by mixed-distribution was proposed in order to analyze heterogeneity of
      costs and length of stays within Diagnosis Related Groups (DRGs). A mixed
      distribution model based on Weibull distributions was applied to 791 discharge
      abstracts of French DRG no. 450 (Health Care Financing Administration 3 DRG no.
      316 "Renal failure") from a national database. Three subgroups of cost and length
      of stay were identified. Except for age, clinical criteria significantly linked
      with the long-stay subgroup were the same as those associated with the high-cost
      subgroup: acute renal failure, intensive care, infectious complications, and
      vascular investigations. The identification of factors associated with high
      costs, based on the proposed model, will allow physicians to understand more
      accurately how their choice of specific procedures influences hospital costs.

PMID- 10210244
TI  - Performing cost-effectiveness analysis by integrating randomized trial data with
      a comprehensive decision model: application to treatment of acute ischemic
      stroke.
AB  - A recent national panel on cost-effectiveness in health and medicine has
      recommended that cost-effectiveness analysis (CEA) of randomized controlled
      trials (RCTs) should reflect the effect of treatments on long-term outcomes.
      Because the follow-up period of RCTs tends to be relatively short, long-term
      implications of treatments must be assessed using other sources. We used a
      comprehensive simulation model of the natural history of stroke to estimate long
      term outcomes after a hypothetical RCT of an acute stroke treatment. The RCT
      generates estimates of short-term quality-adjusted survival and cost and also the
      pattern of disability at the conclusion of follow-up. The simulation model
      incorporates the effect of disability on long-term outcomes, thus supporting a
      comprehensive CEA. Treatments that produce relatively modest improvements in the
      pattern of outcomes after ischemic stroke are likely to be cost-effective. This
      conclusion was robust to modifying the assumptions underlying the analysis. More
      effective treatments in the acute phase immediately following stroke would
      generate significant public health benefits, even if these treatments have a high
      price and result in relatively small reductions in disability. Simulation-based
      modeling can provide the critical link between a treatment's short-term effects
      and its long-term implications and can thus support comprehensive CEA.

PMID- 10210245
TI  - Specific learning disorders/neurodevelopmental disorders.

PMID- 10210246
TI  - Levels of cerebrospinal fluid nerve-growth factor differ in infantile autism and
      Rett syndrome.
AB  - Autism and Rett syndrome (RS) are both developmental disorders of unknown origin.
      Autism is a behaviourally defined syndrome. RS, which affects girls only, is
      characterized by a profound learning disability following early normal
      development, with a consistent cluster of clinical features. Differentiation of
      RS from infantile autism in the very early stages of the disorders is not always
      easy. Both syndromes still lack discriminative laboratory markers for accurate
      diagnosis and differentiation. We decided to compare the CSF nerve-growth factor
      (NGF) levels of children with infantile autism and children with RS using enzyme
      linked immunosorbent assay (ELISA). Our findings of mainly normal CSF NGF in
      autism and low to negligible values in RS are in agreement with the different
      morphological and neurochemical findings (brain growth, affected brain areas,
      neurotransmitter metabolism) in the two syndromes. CSF NGF could be used as a
      biochemical marker for differentiation of patients with autism from those with
      RS.

PMID- 10210247
TI  - Comorbidity of autistic spectrum disorders in children with Down syndrome.
AB  - The aim of the study was to identify the comorbidity of autistic spectrum
      disorders in a population of children with Down syndrome (DS). All children with
      DS within a defined population of South Birmingham were identified. The Asperger
      Syndrome Screening Questionnaire and the Child Autism Rating Scale were completed
      and diagnosis made according to ICD-10 criteria following interview and
      observation. Thirty-three of 58 identified children completed the measures, four
      of whom received a diagnosis of an autistic spectrum disorder. This is equivalent
      to a minimum comorbid rate of 7%. The questionnaire items concerning social
      withdrawal, restricted or repetitive interests, clumsiness, and unusual eye
      contact were associated with an autistic disorder. Of the remaining 29
      participating children, 11 also displayed marked obsessional and ritualistic
      behaviours. The comorbid occurrence of autism and DS is at least 7%. It is
      important that these children are identified and receive appropriate education
      and support. A full assessment of social, language, and communication skills and
      behaviour is crucial, particularly in children with DS who appear different from
      other children with DS. Potential mechanisms accounting for this comorbidity are
      discussed.

PMID- 10210248
TI  - Motor coordination and kinaesthesis in boys with attention deficit-hyperactivity
      disorder.
AB  - In the current study, movement ability and underlying kinaesthetic processes of
      boys with attention deficit-hyperactivity disorder (ADHD) were compared with a
      group of control children. Two groups of 16 boys with either predominantly
      inattentive subtype ADHD (ADHD-PI) or combined subtype ADHD (ADHD-C) were
      compared with 16 control boys matched on age and verbal IQ. The findings
      demonstrated that the children with ADHD had significantly poorer movement
      ability than the control children. A high percentage of children with ADHD
      displayed movement difficulties consistent with developmental coordination
      disorder. In addition, the current study found that the type and degree of
      movement difficulty differed between subtypes. Children with ADHD-PI had
      significantly poorer fine motor skill while children with ADHD-C were found to
      experience significantly greater difficulty with gross motor skill. The severity
      of the children's inattentive symptomatology was found to be a significant
      predictor of motor coordination difficulties. Kinaesthetic sensitivity was not
      found to differ significantly between the groups.

PMID- 10210249
TI  - Fingertip forces during object manipulation in children with hemiplegic cerebral
      palsy. I: anticipatory scaling.
AB  - Previous studies of grasping and object manipulation in children with cerebral
      palsy (CP) have suggested a dichotomy in the ability to use anticipatory control
      (planning) of the fingertip force output, depending on the type of sensory
      information (tactile or proprioceptive) on which it is based. The present study
      further explores this issue by testing the ability of 15 children with hemiplegic
      CP aged between 8 and 14 years to scale the fingertip force output in advance
      during the lifting of small objects whose weight and surface texture are varied.
      The results indicate that children with hemiplegia can use anticipatory control
      based on both the weight and texture of the object, but require a greater number
      of trials than age-matched children without CP (control children) before they can
      do so. We suggest that the initial lack of anticipatory control results from an
      indistinct internal representation of the object's physical properties due to
      disturbed sensory mechanisms, which may have direct implications for therapeutic
      intervention.

PMID- 10210250
TI  - Fingertip forces during object manipulation in children with hemiplegic cerebral
      palsy. II: bilateral coordination.
AB  - The present study examines the coordination of fingertip forces during object
      manipulation in both the involved and non-involved hand of 14 children with
      hemiplegic cerebral palsy (CP) aged between 8 and 14 years. While no impairment
      could be observed in the non-involved hand, subtle deficits in the sequencing of
      the grip-lift movement were observed in all children tested in this hand.
      However, they were able to scale the fingertip force output of the non-involved
      hand in advance (use anticipatory control) based on the object's weight. In the
      second experiment in this paper, we tested whether the anticipatory control can
      be generalized across hands. The results indicate that sensory information from
      the non-involved hand can be used for anticipatory scaling of isometric force
      increase during subsequent lifts with the contralateral involved hand. These
      findings suggest that the initial lack of anticipatory control usually observed
      in the involved hand of children with hemiplegic CP is likely to be based on
      disturbed sensory input.

PMID- 10210251
TI  - Measuring developmental and functional status in children with disabilities.
AB  - This study compared performance on the Functional Independence Measure for
      Children (WeeFIM), the Battelle Developmental Inventory Screening Test (BDIST),
      and the Vineland Adaptive Behavior Scales (VABS) in children with developmental
      disabilities. The three instruments were administered to 205 children with
      identified disabilities. All 205 children were tested using the WeeFIM
      instrument. The BDIST was administered to 101 children and the VABS to the
      remaining 104 children. Administration was counterbalanced and randomized across
      all three instruments. A proportional sampling plan was used to select the 205
      children, who ranged in age from 11 to 87 months. A variety of medical diagnoses
      and levels of severity of motor, cognitive, and communication impairments were
      systematically included in the sample. Correlations (r) among subscales for all
      three instruments ranged from 0.42 to 0.92. Correlations for total scores ranged
      from 0.72 to 0.94. Analyses of potential moderator variables found no significant
      relation between age and severity of disability (r=0.05) or between socioeconomic
      status (SES) and severity of disability (r=0.21). Correlations with age were
      strongest for those subscale scores involving gross and fine motor skills.
      Correlations with SES and subscale scores ranged from 0.03 to 0.18. The three
      instruments provide important information regarding childhood performance in
      motor, self-care, communicative, cognitive, and social skills. The WeeFIM
      instrument requires less administration time and provides information directly
      relevant to evaluating functional outcomes for children with disabilities and
      their families.

PMID- 10210252
TI  - Predictors of developmental delay at 18 months and later school achievement
      problems.
AB  - The aim of the study was to examine the predictive value of the variables of
      parental assessment score, pre-, peri-, and postpartum optimality, sex,
      socioeconomic status (SES), and maternal education with respect to developmental
      delay at 18 months, and intellectual disability and school achievement problems
      at 8 and 14 years. The sample studied comprised 101 children (53 low scorers and
      48 controls) originally from a total population of 2783 children assessed by
      their parents at 18 months using a screening instrument. Data were analysed by
      logistic regression. The results yielded moderate but statistically significant
      correlations between predictor and outcome variables. Optimality score and
      maternal education were the best predictors of developmental delay at 18 months.
      At 8 years, parental assessment score and maternal education constituted the best
      predictors of school achievement problems. At 14 years, SES together with
      parental assessment score were included in the model, when school achievement
      problems were predicted. Parental assessment score showed the strongest
      association with school achievement problems at both 8 and 14 years, when
      children with intellectual disability were included in the analysis. The
      exclusion of children with intellectual disability from the analyses yielded a
      stronger association between maternal education (at 8 years) and SES (at 14
      years) and school achievement problems. The overall classification accuracy of
      the models varied between 67% and 88%. Specificity varied from 65% at 18 months
      to 95% at 14 years. Sensitivity varied from 70% at 18 months and 55% (all cases)
      and 42% (children with intellectual disability excluded) at 14 years.

PMID- 10210254
TI  - Pharmacological management of convulsive status epilepticus in children.

PMID- 10210253
TI  - Long-term follow-up of an individual with vitamin B6-dependent seizures.
AB  - We report on a 31-year-old female with vitamin B6-dependent seizures whose
      seizure onset was in the neonatal period. Her elder brother had the same disorder
      and died in infancy. Administration of vitamin B6 was initiated in the postnatal
      period. At the age of 12 years 1 month, 2 months after withdrawal of vitamin B6,
      visual seizures began to occur frequently. Myoclonic seizures and occasional
      generalized convulsive seizures were also observed. At the same time,
      photoparoxysmal response and spontaneous diffuse spike-wave bursts were seen on
      her EEG. Myoclonic seizures were provoked by intermittent photic stimulation
      during the EEG. It is distinctive that visual seizures were one of the main
      seizure types in this patient, that her clinical course was relatively benign,
      and that she has normal intellectual outcome.

PMID- 10210255
TI  - 'Unexpected artistic creativity'.

PMID- 10210256
TI  - 'Multidisciplinary appraisal of the British Institute for Brain Injured Children,
      Somerset, UK'.

PMID- 10210258
TI  - Current articles.

PMID- 10210257
TI  - 'Who is a visually impaired child? A model is needed to address this question for
      children with cerebral visual impairment'.

PMID- 10210259
TI  - Site-directed polyethylene glycol modification of trichosanthin: effects on its
      biological activities, pharmacokinetics, and antigenicity.
AB  - Trichosanthin (TCS), a type I ribosome-inactivating protein (RIP), was modified
      with polyethylene glycol (PEG) in order to reduce its antigenicity and prolong
      its half-life. Computer modeling identified three potential antigenic sites
      namely Q219, K173 and S7. By site-directed mutagenesis, these sites were changed
      into cysteine through which PEG can be covalently attached. The resulting TCS had
      a PEG coupled directly above one of its potential antigenic determinants, hence
      masking the antigenic region and prevent binding of antibodies specific to this
      site. In general, mutation did not bring about significant changes in ribosome
      inactivating activity, cytotoxicity, and abortifacient activity of TCS. However,
      the in vitro activities of PEG modified (PEGylated) TCS muteins were 3-20 folds
      lower and the in vivo activity 50% less than that of nTCS. Pharmacokinetics study
      indicated that all three PEGylated TCS muteins showed 6-fold increase in mean
      residence time as compared to unmodified muteins. The binding affinity of an IgE
      monoclonal antibody (TE1) to TCS was greatly reduced after PEG modification
      (PEGylation) at position Q219, suggesting that TE1 recognized an epitope very
      near to residue Q219. PEGylated TCS muteins induced similar IgG response but 4-16
      fold lower IgE response in mice compared with nTCS.

PMID- 10210260
TI  - The anti-inflammatory effects of quinolinic acid in the rat.
AB  - Quinolinic acid (QUIN) levels are elevated in patients and animals suffering from
      chronic infectious diseases. In the present study, male Sprague-Dawley rats were
      used to test the anti-inflammatory effects of QUIN using the carrageenan (CGN)
      induced paw edema assay and the CGN sponge assay. Results of these studies
      indicate that QUIN (30, 100 or 300 mg/kg i.p.) caused a reduction of carrageenan
      induced inflammation by as much as 80% at the highest dose. Moreover, QUIN
      reduced exudate volume and inhibited leukocyte migration in the sponge granuloma
      assay. In another experiment, the anti-inflammatory activity of QUIN was
      eliminated in adrenalectomized rats. QUIN did not reduce edema caused by
      arachidonic acid, bradykinin or compound 48/80. Neither morphine nor naloxone
      altered the anti-inflammatory activity of QUIN. These results may suggest that
      QUIN exerts its anti-inflammatory activity through a direct action on neutrophils
      or vascular permeability.

PMID- 10210261
TI  - Characterization of [3H]Met-enkephalin-Arg6-Phe7 binding to multiple sites in rat
      and guinea pig cerebellum.
AB  - [3H]Met-enkephalin-Arg6-Phe7 (MERF) has been shown to label opioid (kappa2 and
      delta) and sigma2 sites in rat and frog brain membrane preparations, and no
      specific binding to kappa1 opioid receptors could be established (refs. 6 and 8).
      In this study the binding was examined in rat cerebellar membranes which are
      relatively rich in kappa2-sites, and in guinea pig cerebellar preparations where
      kappa1 opioid receptors are almost exclusively present. In accordance with our
      previous results, [3H]MERF binding could not be displaced in guinea pig
      cerebellar membranes neither with U-69,593 nor with naloxone or levorphanol
      suggesting no interaction with opioid sites, nevertheless a Kd of 2.8 nM was
      calculated in cold saturation experiments. In rat cerebellar membrane fractions
      about the half of the specific [3H]MERF binding sites was inhibited by opiate
      alkaloids such as naloxone, ethylketocyclazocine, or bremazocine. This portion of
      the heptapeptide binding sites was stereoselective as demonstrated by the
      difference in the affinities of the enantiomeric compounds levorphanol and
      dextrorphan, therefore it would represent an opioid site. In both tissues (-)N
      allyl-normetazocine (SKF-10,047), which is also considered as sigma2 ligand,
      displayed the highest affinities. Among opioid peptides beta-endorphin and
      dynorphin(1-13) showed the highest potencies, displacing [3H]MERF also from its
      non-opioid sites. It was concluded therefore that [3H]MERF does not bind to
      kappa1 sites, and besides kappa2-opioid sites substantial binding to peptide
      preferring non-opioid sites, and/or sigma2 receptors also occurs.

PMID- 10210262
TI  - Effects of vesnarinone on cytokine production and activation of murine microglia.
AB  - Tumor necrosis factor alpha (TNF alpha) is considered to play a critical role in
      the development of various pathological processes in the central nervous system
      (CNS), such as neuronal degeneration, demyelination and gliosis. In order to
      search for agents which suppress TNF alpha production in the CNS for future
      treatment of these pathological conditions, the effects of a synthetic oral
      inotropic agent, vesnarinone, on murine microglia were examined. Vesnarinone
      significantly suppressed TNF alpha production by microglia in a dose-dependent
      manner, without affecting their viability, enzyme activity or expression of the
      major histocompatibility complex. Since the reported maximum serum concentration
      is high enough to suppress TNF alpha production in vitro (about 20 microM) after
      oral administration of the therapeutic dose of vesnarinone, this drug will be
      useful to treat intractable neurological diseases such as neurodegenerative
      disorders, multiple sclerosis or HIV-related neurological disorders.

PMID- 10210263
TI  - Halogenated derivatives of boldine with high selectivity for alpha1A
      adrenoceptors in rat cerebral cortex.
AB  - The selectivity of 3-nitrosoboldine and different halogenated derivatives of
      boldine (3-bromoboldine, 3,8-dibromoboldine and 3-chloroboldine) for alpha1
      adrenoceptor subtypes was studied by examining [3H]-prazosin competition binding
      in rat cerebral cortex. In the competition experiments [3H]-prazosin binding was
      inhibited completely by all the compounds tested. The inhibition curves displayed
      shallow slopes which could be subdivided into high and low affinity components.
      The relative order of affinity and selectivity for alpha1A-adrenoceptors was 3
      bromoboldine = 3,8-dibromoboldine = 3-chloroboldine > boldine > 3-nitrosoboldine.
      The competition curves for 3-bromoboldine remained shallow and biphasic following
      chloroethylclonidine treatment. Whereas the relative contribution of the high
      affinity sites increased, the 3-bromoboldine affinities at its high and low
      affinity sites remained similar to those obtained in untreated membranes. 3
      Bromoboldine, 3,8-dibromoboldine, 3-chloroboldine and 3-nitrosoboldine did not
      significantly displace [3H]-(+)-cis-diltiazem binding to rat cerebral cortex
      membranes. This activity was lower than that shown by boldine. Compared to
      boldine, halogen (bromine or chlorine) substitution at position 3 increases the
      alpha1A-adrenoceptor subtype selectivity and decreases the affinity for the
      benzothiazepine binding site at the calcium channel. Further halogen substitution
      at position 8 did not significantly improve this activity with respect to 3
      bromoboldine. In contrast, the NO substitution at position 3 of boldine (3
      nitrosoboldine) gives a loss of affinity and selectivity for alpha1-adrenoceptor
      subtypes.

PMID- 10210264
TI  - NXX-066 in patients with Alzheimer's disease: a bridging study.
AB  - Reduced cholinergic transmission is a key neurotransmitter dysfunction in
      Alzheimer's Disease (AD). NXX-066, a physostigmine analog and
      acetylcholinesterase (AChE) inhibitor, has demonstrated activity in animal models
      of memory function, and was well tolerated in healthy subjects up to a single
      dose of 64 mg and multiple doses of 60 mg QD for seven days. Since AChE
      inhibitors are often tolerated differently in AD patients than in healthy
      volunteers, a randomized, placebo-controlled, double-blind, single-center,
      inpatient bridging study was conducted to determine the maximum tolerated dose
      (MTD) of NXX-066 in the target patient population. Seven consecutive panels of
      eight AD patients each (6 active, 2 placebo) received fixed oral doses of NXX-066
      (20, 30, 40, 50, 60, 70, or 80 mg BID) for seven days. Initiation of each
      subsequent panel (dose group) was contingent upon the tolerability of lower dose
      levels. The MTD was determined to be 70 mg BID when four of six patients
      receiving 80 mg BID were prematurely discontinued from the study due to nausea
      and/or vomiting, accompanied in some patients by mild to moderate dizziness,
      headache, asthenia, and gastric symptoms. Wide variability in plasma levels of
      NXX-066 was observed in all dose panels. AChE inhibition in whole blood
      correlated with both maximum plasma concentration and dose; however, AChE
      inhibition was not predictive of adverse events. In this study, AD patients
      tolerated larger daily doses of NXX-066 on a BID regimen than healthy normal
      subjects had tolerated with QD dosing. Further studies are warranted to examine
      whether differing tolerability between patients and healthy subjects or the
      reduced dosing interval explains these findings.

PMID- 10210265
TI  - The procedure of polymerase chain reaction-restriction fragment-single strand
      conformation polymorphism analysis by Hha I/Hinc II to detect mitochondrial DNA
      mutations.
AB  - We reported 56 mitochondrial DNA (mtDNA) mutations in Japanese compared with the
      Cambridge Sequence by polymerase chain reaction-restriction fragment-single
      strand conformation polymorphism (PCR-RF-SSCP) analysis. Here we report the
      principle and the detailed procedures of PCR-RF-SSCP analysis. Restriction map of
      the 15,673 bp PCR product of mtDNA was designed by MacMolly Tetra, and Hha I and
      Hinc II were selected. Restriction fragment length polymorphism (RFLP) analysis
      of 15,673 bp PCR products by Hha I/Hinc II revealed one common pattern and 10
      polymorphic patterns compared with the prediction based on the Cambridge
      Sequence. When the samples were electrophoresed by SSCP analysis, DNA fragments
      of 912 bp, 772 bp, 761 bp, 634 bp, 431 bp, 327 bp, 226 bp and 171 bp showed 6, 4,
      5, 4, 5, 7, 2 and 3 polymorphic patterns, respectively. The determinations of
      nucleotide sequence of these 46 polymorphic patterns revealed 56 mutations
      compared with the Cambridge Sequence and 7 of these mutations were common in
      Japanese. Among these, 20 mutations have not been reported before.

PMID- 10210267
TI  - Transport kinetics of leucine enkephalin across Caco-2 monolayers: quantitative
      analysis for contribution of enzymatic and transport barrier.
AB  - In this study, we determined the activities of four aminopeptidases such as
      aminopeptidase B (APB), M (APM), N (APN) and dipeptidylpeptidase IV (DPP IV) in
      Caco-2 cells and compared with those in the rat intestinal mucosae. The
      activities of APB, APM and APN appeared to be highest in rat small intestinal
      mucosa, while DPP IV activity was much higher in Caco-2 cells than that in the
      rat intestinal mucosa. Next the inhibitory effects of various protease inhibitors
      were examined in Caco-2 homogenate. Three tested inhibitors, bacitracin,
      amastatin and puromycin, effectively inhibited the activities of APM, APN and DPP
      IV except for APB. Further, we quantitatively evaluated the permeation and
      degradation properties of leucine enkephalin (Leu-Enk) in the presence or absence
      of inhibitors in Caco-2 monolayer system. Leu-Enk had a high degradation
      clearance (CLd) and a low permeation clearance (CLp) in Caco-2 monolayers. This
      finding indicates that the very rapid degradation of Leu-Enk on the apical side
      of Caco-2 monolayers was due to aminopeptidases. However, these protease
      inhibitors besides sodium glycocholate were able to reduce the CLd values
      markedly, thereby increasing the permeation amount of Leu-Enk across Caco-2
      monolayers. In particular, amastatin significantly decreased the CLd value and
      increased the CLp value. This enhanced CLp value was further increased by the
      coadministration with an absorption enhancer, EDTA or laurylmaltoside. These
      findings are relevant to the oral administration of peptide drugs and to
      developing an efficient oral delivery system.

PMID- 10210266
TI  - Expression of cyclooxygenase-2 in rat vascular smooth muscle cells is unrelated
      to nuclear factor-kappaB activation.
AB  - The promoter region of cyclooxygenase-2 (COX-2) gene contains binding sites for a
      number of important transcription factors including cyclic AMP response element,
      nuclear factor-IL6, nuclear factor-kappaB (NF-kappaB) and TGF-beta response
      element. Several reports have documented that the activation of NF-kappaB
      triggers the expression of COX-2 gene. In the present study, NF-kappaB was
      activated by TNF-alpha in rat aortic smooth muscle cells as demonstrated by
      electrophoretic mobility shift assay. The activity of NF-kappaB induced by TNF
      alpha was blocked by calpain inhibitor I, a potent NF-kappaB inhibitor. However,
      the activation of NF-kappaB was not related to the expression of COX-2 induced by
      TNF-alpha since calpain inhibitor I blocked the activation of NF-kappaB but not
      the expression of COX-2 mRNA or protein. Mutation of rat COX-2 NF-kappaB-like
      sites in the promoter region did not significantly reduce the promoter activity.
      These results suggest that the transcriptional regulation of COX-2 expression by
      NF-kappaB depends upon the types of cells studied and that activation of this
      transcription factor alone does not play an important role in the expression of
      COX-2 in rat smooth muscle cells.

PMID- 10210268
TI  - Systemically administered capsazepine prevents the capsaicin-induced functional
      desensitization and loss of substance P-like immunoreactivity (SP-LI) in guinea
      pig bronchi.
AB  - In this study, we investigated whether the systemically administered capsazepine
      can prevent the capsaicin-induced desensitization ex vivo in guinea-pig bronchi.
      Pretreatment with capsaicin (2.5, 5 and 10 mg/kg, s.c.) induced the functional
      desensitization and the loss of substance P-like immunoreactivity (SP-LI) with a
      similar potency (ED50: 3.31 +/- 0.57 and 4.81 +/- 0.89 mg/kg, respectively) in
      isolated guinea-pig bronchi. Capsazepine (30 mg/kg, s.c.) co-administered with
      capsaicin (5 mg/kg, s.c.) prevented the capsaicin (5 mg/kg, s.c.)-induced
      functional desensitization and loss of SP-LI. These results suggest that
      capsazepine can antagonize systemically the desensitizing action of capsaicin at
      the level of receptor, preventing the loss of SP-LI and the establishment of
      functional desensitization in guinea-pig bronchi.

PMID- 10210269
TI  - Lack of effect of flurothyl, a non-anesthetic fluorinated ether, on rat brain
      synaptic plasma membrane calcium-ATPase.
AB  - Plasma membrane Ca2+-ATPase (PMCA), a regulator of intracellular calcium, is
      inhibited by volatile anesthetics and by xenon and nitrous oxide. Response of a
      cellular system to anesthetics, particularly to volatile agents, raises the
      question of non-specific, even toxic, side effects unrelated to anesthetic
      action. Compounds with chemical and physical properties similar to halogenated
      anesthetics, but which lack anesthetic effect, have been used to address this
      question. We have compared the effects of halothane and flurothyl, a non
      anesthetic fluorinated ether, on PMCA Ca2+ transport across isolated brain
      synaptic plasma membranes (SPM). Flurothyl, at concentrations predicted by the
      Meyer-Overton curve to range from 0.4 to 2.6 MAC (minimum alveolar
      concentration), had no significant on PMCA activity. In contrast halothane, 1.3
      MAC, reduced Ca2+ transport 30 to 40%. These findings provide further evidence
      for a specific effect of inhalation anesthetics on neuronal plasma membrane Ca2+
      ATPase.

PMID- 10210270
TI  - Different antiamebic antibody isotype patterns in the large and small intestine
      after local and systemic immunization of mice with glutaraldehyde fixed Entamoeba
      histolytica trophozoites.
AB  - We have determined the major immunoglobulin isotypes (IgG, IgA, IgM) of
      antiamebic antibodies induced in the serum and in the large and small intestine
      after local (oral and rectal) or systemic (intraperitoneal and intramuscular)
      immunization of mice with glutaraldehyde-fixed Entamoeba histolytica trophozoites
      (GFT). IgA predominated in the small intestine after immunization through all
      routes, whereas in the large intestine similar antibody levels of the major
      isotypes were induced by rectal, intraperitoneal and intramuscular immunization.
      The intramuscular route elicited intestinal responses lower than those induced by
      the rectal and intraperitoneal routes, but higher than the slight IgA antibody
      increase observed after oral immunization. The differences in antiamebic antibody
      response patterns at the large and small intestine suggest that there are
      different mucosal effector compartments. They also indicate that isotype analysis
      of mucosal antibodies from the sites where an infectious agent resides is needed
      to evaluate whether a vaccine candidate induces responses of higher protective
      value in the appropriate site, and that the study of antibody responses must not
      be limited to sampling the serum or mucosal sites distant to the relevant one.

PMID- 10210271
TI  - Protection of calcitonin gene-related peptide-mediated preconditioning against
      coronary endothelial dysfunction induced by reperfusion in the isolated rat
      heart.
AB  - This study was designed to explore the protective effect of ischemic
      preconditioning on reperfusion-induced coronary endothelial dysfunction, with a
      focus on the role of calcitonin gene-related peptide (CGRP) in this effect, in
      the isolated perfused rat heart. Thirty minutes of global ischemia and 30 min of
      reperfusion significantly decreased heart rate, left ventricular pressure, and
      its first derivative and impaired vasodilator responses to acetylcholine.
      Ischemia-reperfusion did not affect vasodilator responses to sodium
      nitroprusside. Preconditioning induced by three cycles of 5 min of ischemia and 5
      min of reperfusion produced a significant improvement in cardiac function
      concomitantly with an amelioration of vasodilator responses to acetylcholine. The
      protective effects of ischemic preconditioning were abolished by CGRP(8-37) (10(
      7) M) , the selective CGRP receptor antagonist. After pretreatment with capsaicin
      (50 mg x kg(-1), s.c.) to deplete endogenous CGRP, the preconditioning effect was
      absent. Pretreatment with exogenous CGRP (5 x 10(-9) M) for 5 min induced a
      preconditioning-like protection. The present study suggests that the
      cardioprotection of ischemic preconditioning is related to the preservation of
      the coronary endothelial cell, and that the protective effect of preconditioning
      is mediated by endogenous CGRP in the isolated perfused rat heart.

PMID- 10210272
TI  - Model development and behavioral assessment of focal cerebral ischemia in rats.
AB  - Stroke in humans is usually focal and occurs in the Middle Cerebral Artery (MCA)
      distribution. There are several rat models that mimic strokes clinically seen in
      human. Severity of ischemia can be determined by occlusion time, arteries
      occluded i.e. MCA alone or combined with one or both Common Carotid Arteries
      (CCA), and/or location of the occlusion. In this study three focal cerebral
      infarctions (stroke) were induced for 90 and 120 minutes due to the occlusion of:
      the MCA alone (MCAo); MCA plus unilateral CCA (MCAo+1CCAo); and MCA plus
      bilateral CCA (MCAo+2CCAo). Histological parameters included infarct lesion size
      and hemispheric swelling. Since functional recovery of clinical deficits in
      stroke often correlates with the efficacy of anti-ischemic therapy, we focused on
      the behavioral recovery. We combined many sources to obtain comprehensive
      guidelines for clinical behavior evaluation. Tests included limb flexion, torso
      twisting, circling, lateral push resistance, beam balancing and walking, hindlimb
      placing, and inverted angle-board gripping. Occlusion lasting 90 minutes was
      found to have consistent and repeatable deficits. Results from our study
      demonstrate 120 minutes of occlusion produced a 60% morality rate and was
      therefore dropped. Body weight changes between groups showed that increased
      occlusion time produced more weight loss. Behavior changes indicated that
      MCAo+2CCAo for 90 minutes demonstrated assessable and consistent clinical
      deficits for the screening of potential therapeutics.

PMID- 10210273
TI  - Polyethylene glycol augments thyroid cAMP responses by fragments from protease
      digested TSAb or TSBAb-IgG.
AB  - In the previous reports, we have demonstrated (1) that polyethylene glycol
      (PEG)(5%) augmented TSAb (thyroid stimulating antibody)-stimulated cAMP responses
      of porcine thyroid cells, and (2) that fragments from papain-digested TSBAb
      (thyroid stimulation blocking antibody) could stimulate thyroid cAMP synthesis.
      Thus, we studied the effect of 5% PEG on cAMP responses stimulated by the
      protease-digested TSAb- or TSBAb-fragments. Stimulatory effect of 5% PEG on cAMP
      production by Fab fragment (Mr 50 KDa) and the retarded fraction (Mr 20 KDa) from
      the gel-filtration on Sephadex G-100 using papain-digested TSAb-IgG unbound to
      Protein A-Sepharose was observed. Similar stimulatory effect of 5% PEG on the
      second fraction (Fc with trace amounts of Fab) in the gel-filtration on Sephadex
      G-100 using papain digested TSAb-IgG bound to Protein A-Sepharose was observed.
      Stimulatory effect of PEG on the second fraction was derived from Fab fragment.
      PEG (5%) also showed stimulatory effect on cAMP production by F(ab')2 fragment
      (Mr 100 KDa) from the gel-filtration on Sephadex G-100 using pepsin-digested TSAb
      IgG unbound to Protein A-Sepharose. PEG (5%) augmented cAMP responses by both Fab
      and the retarded fractions from the gel-filtration using papain-digested TSBAb
      IgG unbound to Protein A when these fractions could stimulate cAMP synthesis. In
      conclusion, PEG (5%) augments cAMP responses stimulated by F(ab')2, Fab and the
      smaller molecular components (Mr 20 KDa) separated from protease-digested TSAb
      IgG. PEG also augments cAMP responses stimulated by Fab and the smaller molecular
      components with thyroid stimulating activity separated from papain-digested TSBAb
      IgG.

PMID- 10210274
TI  - Potentiation of haloperidol catalepsy by microinjections of nicotine into the
      striatum or pons in rats.
AB  - It was reported that systemic administration of nicotine in rats potentiated the
      cataleptogenic effect of haloperidol. Moreover, addition of nicotine to the
      treatment with haloperidol in patients suffering from the Gilles de la Tourette's
      syndrome resulted in reduction in frequency and severity of tics. In the present
      article we report results of experiments aimed at investigating the role of
      striatum and pontine reticular formation in the synergistic relations between the
      two drugs. Nicotine was microinjected directly into the striatum or pontine
      reticular formation of rats and its cataleptogenic effects were studied when
      given alone or in combination with systemical injections of haloperidol. It was
      found that nicotine has cataleptogenic effects when microinjected both into the
      striatum and pontine reticular formation. The synergism between the two drugs
      occurred both after microinjections into the striatum and pontine reticular
      formation.

PMID- 10210275
TI  - Differential expression of c-fos mRNA in the rat neocortex by in situ
      hybridization.
AB  - The c-fos mRNA expression pattern in rat neocortex, was determined in the rat
      kept in a 12:12 light/dark cycle, in constant dark, or in constant light by in
      situ hybridization. At the beginning of the light period, c-fos mRNA was induced
      both in the neocortex and suprachiasmatic nucleus (SCN). Transiently increased c
      fos mRNA expression was detected from 0830 to 0900 and soon declined to basal
      levels. Immediately prior to the beginning of the dark period, c-fos mRNA
      expression also increased and remained elevated in the neocortex following the
      dark period. In the constant dark group, c-fos mRNA expression showed no
      transient elevation at the beginning of the light period. On the other hand, c
      fos mRNA expression in the constant light group increased during their subjective
      dark period as well as normal light/dark cycle. These results demonstrate a
      circadian pattern of c-fos mRNA expression in the neocortex which is similar to
      that observed previously in the inner and outer nuclear layers of the retina.

PMID- 10210277
TI  - Effects of intrathecal galanin on nociceptive responses in rats with
      mononeuropathy.
AB  - The present study was performed on rats with experimental mononeuropathy induced
      by left common sciatic nerve loose ligation. Unilateral sciatic nerve loose
      ligation induced decreases of the hindpaw withdrawal latency to the hot-plate
      test, cold-plate test and the Randall Selitto test. Sciatic nerve loose ligation
      induced hyperesponsiveness to touch at room temperature also. Intrathecal
      administration of either 3 or 6 nmol of galanin, but not 1 nmol, induced
      significant bilateral increases in hindpaw withdrawal latencies to the hot-plate
      test, cold-plate test and the Randall Selitto tests in rats with left
      mononeuropathy. The results indicate that galanin may play important roles in
      transmission of presumed nociceptive information in the spinal cord of
      mononeuropathic rats.

PMID- 10210276
TI  - Catecholamine metabolism inhibitors and receptor blockades only partially
      suppress cardiac hypertrophy of juvenile visceral steatosis mice with systemic
      carnitine deficiency.
AB  - To clarify the mechanism of cardiac hypertrophy in carnitine-deficient JVS mice,
      we studied the possible role of catecholamine metabolism. Cardiac hypertrophy
      occurs 2 weeks after birth. The turnover of norepinephrine in the ventricles of
      JVS mice at 2 weeks was 3 times that of control, but it was not different from
      control at 5 days when the heart weight was not changed. To evaluate the
      accelerated norepinephrine turnover, we examined the effects of catecholamine
      metabolism inhibitors (alpha-methyltyrosine and 6-hydroxydopamine) and
      catecholamine receptor blockades (propranolol, prazosin and yohimbine) on the
      ratio of heart weight to body weight (HW/BW) and on the augmented expression of
      atrial natriuretic peptide (ANP) and the down-regulated carnitine deficiency
      associated gene expressed in ventricle (CDV-1). The HW/BW ratio in JVS mice
      treated with catecholamine metabolism inhibitors and receptor blockades was
      significantly lower than in JVS mice without treatment, but still higher than in
      controls treated with each drug and in JVS mice treated with carnitine. The HW/BW
      ratio of JVS mice with propranolol was not significantly different from that of
      JVS mice treated with catecholamine metabolism inhibitors and was significantly
      lower than that of JVS mice treated with prazosin and yohimbine. Northern blot
      analysis showed that the altered expression of ANP and CDV-1 was not corrected in
      the ventricles of JVS mice treated with any of the drugs except carnitine. These
      results suggest that the catecholamine metabolism accelerated in JVS mice
      ventricles at 2 weeks is not the major cause of cardiac hypertrophy, but probably
      promotes cardiac hypertrophy mainly through the beta-adrenergic signaling
      pathway. The aberrant gene expression of ANP and CDV-1 found in JVS mice seems to
      be independent of catecholamine metabolism, and mediated primarily by the
      systemic carnitine deficiency.

PMID- 10210278
TI  - Colon-specific delivery of R68070, a new thromboxane synthase inhibitor, using
      chitosan capsules: therapeutic effects against 2,4,6-trinitrobenzene sulfonic
      acid-induced ulcerative colitis in rats.
AB  - The objective of this study was to estimate the therapeutic effects of R68070, a
      new thromboxane synthase inhibitor, on 2,4,6-trinitrobenzenesulfonic acid sodium
      salt (TNBS)-induced ulcerative colitis in rats. We also examined the acceleration
      of the healing effect of R68070 with chitosan capsules to achieve its colon
      specific delivery. The colonic injury and inflammation were assessed by measuring
      the myeloperoxidase (MPO) activities, colon wet weight/body weight (C/B) ratio
      and the damage score, respectively. These markers were decreased by the oral
      administration of R68070 with chitosan capsules and carboxymethyl-cellulose (CMC)
      suspension. The therapeutic effects of R68070 against ulcerative colitis were
      observed in both dosage forms in a dose dependent manner. In addition, its
      therapeutic effects were increased by the use of chitosan capsules, compared with
      CMC suspension. These results suggest that chitosan capsule might be a very
      useful dosage form for the colon-specific delivery of R68070 as an anti
      inflammatory drug and for the therapy of ulcerative colitis.

PMID- 10210279
TI  - Nociceptin receptor activation inhibits tachykinergic non adrenergic non
      cholinergic contraction of guinea pig isolated bronchus.
AB  - We studied the action of nociceptin (NC) on the atropine-resistant contractions
      of the guinea pig isolated bronchus evoked by the electrical field stimulation
      (EFS), an effect that is mediated by the activation of excitatory non adrenergic
      non cholinergic (eNANC) nerves and the subsequent release of tachykinins. The
      functional site by which NC acts in this preparation was investigated using few
      different NC receptor agonists and the newly discovered NC receptor antagonist,
      [Phe1psi(CH2-NH)Gly2]NC(1-13)NH2 ([F/G]NC(1-13)NH2). NC inhibited in a
      concentration dependent manner (pEC50 7.14; Em - 87 +/- 3% of control values) EFS
      induced contractions. NC effect was mimicked by the NC analogues, NCNH2 and NC(1
      13)NH2, but not by NC(1-9)NH2. NC (1 microM) did not affect the contractile
      effects of exogenously applied neurokinin A (1 microM). [F/G]NC(1-13)NH2 (10
      microM) completely prevented the inhibition induced by NC (1 microM), whereas
      naloxone (1 microM) was found inactive. Both naloxone and ([F/G]NC(1-13)NH2 were
      per se inactive on basal resting tone as well as on the electrically induced
      contractions. The present findings show that NC inhibits the atropine-resistant
      EFS-induced contraction in the guinea pig bronchus by inhibiting eNANC nerves,
      and suggest the presence of NC receptors, distinct from opioid receptors, on the
      nerves of the guinea pig bronchus.

PMID- 10210280
TI  - Growth inhibition of capsaicin on HeLa cells is not mediated by intracellular
      calcium mobilization.
AB  - The effects of capsaicin on cellular growth and intracellular calcium
      mobilization were examined in human cervical carcinoma derivation, HeLa cells.
      Capsaicin inhibited cellular growth and increased intracellular calcium level in
      HeLa cells. This capsaicin-induced intracellular calcium concentration rise was
      blocked by capsazepin, vanilloid (capsaicin) receptor antagonist. But, an
      intracellular calcium chelator BAPTA/AM did not block the inhibitory effect of
      capsaicin on cellular growth. These observations suggest that intracellular
      calcium mobilization is not required for the capsaicin-induced inhibition of
      cellular growth.

PMID- 10210281
TI  - Human ovary and placenta express messenger RNA for multiple activin receptors.
AB  - In the present study, we examined the expression of activin receptor (ActR) mRNAs
      in human ovary and placenta. Primers specific for two type I and two type II
      activin receptors (ActR-I, ActR-IB, ActR-II, and ActR-IIB) were used in
      polymerase chain reaction (PCR) to amplify cDNAs prepared from granulosa-luteal
      cells, placental tissues and isolated trophoblast cells. PCR products with the
      expected sizes for ActR-I, ActR-IB, ActR-II, and ActR-IIB mRNAs were detected in
      freshly dissociated and 5-day cultured granulosa-luteal cells; and in trophoblast
      cells from both first trimester and term placentas. The identity of these PCR
      products were confirmed by Southern blot hybridization, as well as cloning and
      sequencing. These results suggest that multiple activin receptors are present in
      human ovary and placenta and may mediate activin function in these tissues. The
      demonstration of activin receptor mRNAs in granulosa-luteal and trophoblast cells
      further supports the notion that activin is an important local regulator in the
      human ovary and placenta.

PMID- 10210282
TI  - Differential regulation of intracellular Ca2+ signalling induced by high K+ and
      endothelin-1 in single smooth muscle cells of intact canine basilar artery:
      detection by means of confocal laser microscopy.
AB  - Changes in intracellular calcium concentration ([Ca2+]i) in smooth muscle cells
      play the key role in regulation of vascular smooth muscle tone and pathogenesis
      of cerebral vasospasm. In this study, we adopted the confocal laser microscopy to
      detect the fluorescence signals arising from the individual smooth muscle cells
      of canine basilar artery. Ring preparations were made, loaded with fluo-3 and
      changes in fluorescence induced by high K+ and endothelin-1 (ET-1) were measured
      by confocal laser microscopy. In some unstimulated smooth muscle cells Ca2+ waves
      arising from discrete region of the cell propagated to the whole cell with a
      velocity of approximately 10 microm/s. High K+ (80 mmol/L) induced a rapid rise
      in [Ca2+]i, the peak level being consistently reached approximately 10 s after
      stimulation. In contrast, the time to peak level of [Ca2+]i induced by ET-1 (0.3
      micromol/L) varied widely between 13 and 26 s among individual cells, an
      indication that the extent of nonuniform coordination of increases in [Ca2+]i in
      individual cells may be partly responsible for the different time courses of
      tension development of vascular smooth muscle in response to the vasoactive
      stimulants. The increase in [Ca2+]i induced by ET-1 was transient but a
      pronounced and sustained contraction developed further in response to ET-1. Thus
      ET-1 has a biological property as a potential candidate to elicit cerebral
      vasospasm. Confocal laser microscopy could be a useful tool to measure the
      changes in [Ca2+]i in individual smooth muscle cells of cerebral artery.

PMID- 10210283
TI  - Analysis of immunomodulating cytokine mRNAs in the mouse induced by mushroom
      polysaccharides.
AB  - The immunomodulating action of two mushroom antitumor polysaccharides,
      polysaccharide-protein complex (PSPC) and lentinan, was elucidated through
      analysing the expression profile of cytokines during a time course (0 h to 48 h)
      after their administration. Among the 5 cytokine genes, the induction of a marked
      increase in the mRNA levels of IL-1alpha, IL-1beta, TNF-alpha, IFN-gamma and M
      CSF by PSPC and lentinan was observed in the peritoneal exudate cells and
      splenocytes. However, the time point of their increased production was different
      after PSPC and lentinan administration.

PMID- 10210284
TI  - Induction of apoptosis in mouse thymocytes by microcolin A and its synthetic
      analog.
AB  - Microcolin A (Mic-1), a marine-derived compound, has been shown to be a novel
      antiproliferative and immunosuppressive agent. We investigated the ability of Mic
      1 and its chemosynthetic analog, microcolin A3 (Mic-3), to induce apoptosis in
      murine thymocytes. Following incubation of the cells with Mic-1 (10-100 nM) or
      Mic-3 (10-100 nM), internucleosomal DNA fragmentation in apoptotic cells was
      detected by agarose gel electrophoresis and the diphenylamine (DPA) assay; the
      presence of hypodiploid nuclei assessed by propidium iodide (PI) staining; and
      the percentages of apoptotic and necrotic cells quantified by morphological
      observation and fluorescein labeled annexin-V binding. Our results show that both
      Mic-1 and Mic-3 are potent inducers of apoptosis in thymocytes depending on drug
      concentration and time of exposure, with Mic-3 being more potent than Mic-1 in
      the induction of apoptosis. Furthermore, flow cytometric analysis using
      monoclonal antibodies specific to thymocyte subpopulations showed that the
      proportion of the early immature CD4+ CD8+ T-cell subpopulation in thymocytes was
      selectively decreased by both agents with a corresponding increase of other
      subpopulations, indicating that CD4+ CD8+ T cells are the most likely targets of
      Mic-1 and Mic-3. These in vitro results suggest that the antiproliferative and
      immunosuppressive properties of both compounds are possibly associated with
      apoptosis-inducing events and imply that they may have additional potential value
      as antineoplastic agents.

PMID- 10210285
TI  - Lack of regression of atherosclerotic lesions in phytosterol-treated apo E
      deficient mice.
AB  - We evaluated the effects of a phytosterol mixture (FCP-3PI) on the regression of
      atherosclerotic lesions in male apo E-deficient mice. Atherosclerosis was induced
      in fifteen mice by a "Western-type" diet containing 9% (w/w) fat and 0.15% (w/w)
      cholesterol over a period of 18 weeks (Induction phase). Then, two mice were used
      to evaluate the development of atherosclerosis, and the rest was divided into the
      control (n=6) and treated (n=7) groups. The control group was fed mouse chow
      (4.5% w/w fat) and the treated group fed the same chow supplemented with 2% (w/w)
      FCP-3PI for an additional 25 weeks (Regression phase). The mice developed severe
      hypercholesterolemia and advanced atherosclerotic lesions over the induction
      phase. During the first 6 weeks of regression phase, plasma cholesterol
      concentrations decreased at a similar rate (35%) in both groups of control and
      phytosterol-treated mice. Although evidence of lesion regression was not observed
      in either group of mice, the treated group had slightly smaller lesion size than
      the controls. During the induction phase, each mouse developed atherosclerotic
      lesions averaging 0.025 mm2 per week. However, during the regression phase, this
      was decreased to approximately one fifth and one third in the treated and control
      groups, respectively. Thus, compared to the end of the induction phase, the
      control group had a 40% increase in the lesion size, while this increase was only
      28% in the treated animals. In conclusion, our previous findings along with a
      small decrease in the atherosclerotic lesion size observed in the treated group
      in the present study suggest that FCP-3PI treatment may slow the development of
      atherosclerotic lesions in apo E-deficient mice; however, a longer regression
      period may yield a greater benefit.

PMID- 10210287
TI  - Some interactions of L-DOPA and its related compounds with glutamate receptors.
AB  - L-DOPA is probably a transmitter and/or modulator in the central nervous system
      (1). L-DOPA methyl ester (DOPA ME) is a competitive L-DOPA antagonist. However,
      it remains to be clarified whether there exist L-DOPAergic receptors. In Xenopus
      laevis oocytes injected with rat brain poly(A)+ RNA, L-DOPA induced small inward
      currents with ED50 of 2.2 mM at a holding potential of -70 mV. The currents were
      abolished by kynurenic acid or CNQX. Similar L-DOPA-currents were seen in oocytes
      co-injected with AMPA receptors, GluRs1,2,3 and 4. In brain membrane
      preparations, L-DOPA inhibited specific binding of [3H]-AMPA with IC50 of 260
      microM. This inhibition was not modified by 200 microM ascorbic acid, an
      antioxidant. L-DOPA did not inhibit binding of [3H]-ligands of MK-801, kainate,
      DCKA and CGP39653. DOPA ME and L-DOPA cyclohexyl ester, a novel, potent and
      competitive antagonist (2), inhibited specific binding of [3H]-MK-801 with
      respective IC50 of 1 and 0.68 mM, but elicited no effect on that of the other
      [3H]-ligands. With low affinities, L-DOPA acts on AMPA receptors, while
      competitive antagonists act on NMDA ion channel domain. L-DOPAergic agonist and
      antagonist may not interact on ionotropic glutamate receptors. DOPA ME-sensitive
      L-DOPA recognition sites (1) seem to differ from glutamate receptors.

PMID- 10210286
TI  - Thyroid stimulating hormone-receptor overexpression in brain of patients with
      Down syndrome and Alzheimer's disease.
AB  - Thyroid hormone abnormalities are strongly associated with Down Syndrome (DS)
      with elevated thyroid stimulating hormone (TSH) levels as the most consistent
      finding. Using subtractive hybridization for gene hunting we found significant
      overexpression of mRNA levels for the TSH-receptor (TSH-R) in brain of a fetus
      with DS. Based upon this observation we determined TSH-R protein levels in five
      brain regions of patients with DS (n=8), Alzheimer disease (AD, n=8) and controls
      (C, n=8). Western blots revealed significantly elevated immunoreactive TSH-R
      protein(s) 40 kD and 61 kD in temporal and frontal cortex of patients with DS
      and, unexpectedly, in AD. Levels for the 40 kD protein in temporal cortex were
      1.00+/-0.036 (arbitrary units+/-SD) in C, 1.35+/-0.143 in DS, 1.52+/-0.128 in AD;
      in frontal cortex: 1.00+/-0.046 in C, 1.10+/-0.03 in DS, 1.10+/-0.038 in AD.
      Levels for the 61 kD protein in temporal cortex were 1.01+/-0.015 in C, 1.47+/
      0.013 in DS, 1.623+/-0.026 in AD; in frontal cortex: 1.02+/-0.020 in C, 1.18 +/
      0.123 in DS, 1.48+/-0.020 in AD. These results show that elevated brain
      immunoreactive TSH-R is not specific for DS and maybe reflecting apoptosis, a
      hallmark of both neurodegenerative disorders, as it is well-documented that the
      thyroid hormone system is involved in the control of programmed cell death.

PMID- 10210288
TI  - Mechanism involved in synergistic adrenocorticotropin response to activating
      protein kinase-A and -C in rat anterior pituitary cells.
AB  - Activation of protein kinase C (PKC) stimulates adrenocorticotropin (ACTH)
      release synergistically in the presence of corticotropin releasing factor (CRF).
      We examined the effect of a cyclic nucleotide-specific phosphodiesterase
      inhibitor, 1-isoamyl-3-isobutylxanthine (IIX), on arginine vasopressin (AVP)
      induced ACTH release and intracellular cAMP accumulation in normal rat anterior
      pituitary cells. IIX alone elevated intracellular cAMP accumulation. IIX
      potentiated AVP-induced ACTH release synergistically without further increase in
      cAMP accumulation, suggesting that synergistic ACTH release has an alternative
      mechanism other than the synergistic elevation of intracellular cAMP accumulation
      which has been reported. Phorbol 12-myristate-13-acetate (PMA) also induced
      synergistic ACTH release when incubated with IIX. IIX had no additional effect on
      ACTH response when incubated with maximal dose of CRF, forskolin or 8
      bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP). Moreover, the combination
      of PMA and 8-Br-cAMP produced synergistic ACTH response. In conclusion, the
      synergistic ACTH release from rat pituitary corticotrophs occurs at least in the
      presence of directly activating events of PKC and PKA as well as PKC-induced
      inhibition of phosphodiesterase activity.

PMID- 10210289
TI  - The effect of follicle-stimulating hormone (FSH) on the expression of FSH
      receptor in cultured rat granulosa cells.
AB  - The acquisition of FSH receptors during folliculogenesis is believed to be a key
      event in the subsequent development of the follicle. The regulation by FSH of FSH
      receptor expression and function were further studied using cultured granulosa
      cells of diethylstilbestrol (DES)-primed immature rats. Incubation of rat
      granulosa cells with FSH led to a reduction in FSH receptor levels for a short
      time (6 h), followed by an increase in FSH receptor levels that reached maximum
      of around 150% of the initial level within 3 days after the addition of FSH. FSH
      stimulation caused a reduced cAMP response to subsequent FSH treatment and a time
      course experiment demonstrated that this response was detectable within 30 min of
      exposure to FSH and reached a plateau after 4 h to 24 h. The recovery of FSH
      responsiveness in cAMP production of granulosa cells was seen after 48 h of FSH
      free interval. Treatment with forskolin (FSK) enhanced the effect of subsequent
      FSH on the production of intracellular cAMP. Treatment with PMA did not affect
      the response to subsequent FSH treatment. These data showed that the FSH is
      essential for the suppression of the FSH receptor function in the adenylyl
      cyclase pathway. Desensitization of cellular response to continuous agonist
      stimulation may occur because of changes in the numbers of FSH receptor, as well
      as changes in the functional properties of the effector system.

PMID- 10210290
TI  - The effects of ischemic preconditioning on resting coronary flow and reactive
      hyperemia: involvement of A1 adenosine receptors.
AB  - During the myocardial protection induced by ischemic preconditioning a reduction
      in myocardial metabolism occurs due to activation of the A1 adenosine receptors.
      This study investigates whether preconditioning changes both resting coronary
      flow and the magnitude of coronary reactive hyperemia and whether A1 adenosine
      receptors are involved in the observed changes. Experiments were performed in 14
      goats (30-50 kg body weight). After the animals were anesthetized with ketamine,
      an electromagnetic flow-probe was used to record blood flow in the left
      circumflex coronary artery. Distal to the probe, an occluder was placed to
      produce ischemic preconditioning and reactive hyperemia. Preconditioning was
      obtained with two periods of 2.5 min of coronary occlusion separated from each
      other by 5 min of reperfusion. Coronary reactive hyperemia was obtained with 15 s
      of occlusion of the artery before and after preconditioning. In a group of goats
      before preconditioning 0.2 mg kg(-1) of 8-cyclopentyl-dipropylxanthine (CPX), an
      A1 adenosine receptor blocker, were given intravenously. In all animals ischemic
      preconditioning did not alter resting coronary flow, but, in the absence of A1
      adenosine receptor blockade, reduced the reactive hyperemic response. The total
      hyperemic flow and the excess/debt flow ratio were reduced by about 25% and 30%
      respectively. The A1 adenosine receptor blockade "per se" did not cause any
      change in the resting flow and in the parameters of the reactive hyperemia.
      Unlike what observed in the absence of blockade, after CPX ischemic
      preconditioning was unable to reduce total hyperemic flow and the excess/debt
      flow ratio. The results suggest that ischemic preconditioning reduces the
      coronary hyperemic response by decreasing the myocardial metabolism through the
      activation of the A1 adenosine receptors.

PMID- 10210291
TI  - Effects of the non-competitive NMDA receptor antagonist ifenprodil on the
      morphine-induced place preference in mice.
AB  - The effects of ifenprodil, a non-competitive N-methyl-D-aspartate (NMDA) receptor
      antagonist, on the morphine-induced place preference were examined in mice.
      Morphine (1-5 mg/kg, s.c.) produced a dose-related place preference in mice. In
      contrast, ifenprodil alone (5-20 mg/kg, i.p.) did not produce either preference
      or aversion for the drug-associated place. Pretreatment with ifenprodil (5-20
      mg/kg, i.p.) suppressed the place preference produced by morphine in a dose
      dependent manner. These results indicate that ifenprodil suppresses the rewarding
      effect produced by morphine.

PMID- 10210292
TI  - The implantable cardiac defibrillator--treatment at last for sudden cardiac
      death?

PMID- 10210293
TI  - The prevalence of malnutrition in elderly hip fracture patients.
AB  - AIM: To determine the prevalence of protein and energy malnutrition in elderly
      patients with a fracture of the proximal femur, in New Zealand. METHODS:
      Consecutive elderly patients (65 years and over) admitted to Christchurch
      Hospital with a fracture of the proximal femur over a four-month period were
      recruited. Nutritional indices were measured within three days of admission.
      These included triceps skinfold thicknesses, mid upper arm circumference, serum
      albumin and pre-albumin. RESULTS: Forty-two per cent of patients had at least
      two, and nine per cent had three, indicators of protein and energy malnutrition
      present on admission. There was no significant difference in the prevalence of
      malnutrition between young old (<80 years) and old old (80 years and over)
      patients. Patients residing in an institution had lower mean protein reserves, as
      indicated by lower corrected arm muscle area (p=0.003) and pre-albumin levels
      (p=0.09), than those living in the community. A drink, rather than a pudding or
      biscuit, was the preferred protein and energy supplement form. Ensure Plus
      (lactose-free) and Fortisip (lactose-free) were the most preferred drink
      supplements. CONCLUSION: Protein and energy malnutrition is common in elderly New
      Zealanders who fracture their femur. The prevalence is comparable to overseas
      data. These patients prefer nutritional supplementation given as a drink.

PMID- 10210294
TI  - Hepatic resection for metastases in colorectal carcinoma.
AB  - AIMS: To outline the role of liver resection in the treatment of colorectal liver
      metastases, with particular reference to hospital morbidity, mortality and
      subsequent survival. METHODS: Seventy major liver resections were performed in
      Wellington by the senior author (RSS) between 1987 and 1997 for colorectal
      metastases. Fifty-three entailed resection alone with intent to cure, nine were
      associated with additional cryotherapy and in eight hepatic arterial chemotherapy
      was subsequently given. Resection was the initial form of liver treatment in all
      70 patients. Patients were aged between 29 and 76 years with a median of 60.0
      years. All patients were judged pre-operatively to have tumour confined to a
      resectable portion of the liver. Data were collected prospectively and held in a
      computerised database. Follow-up was available on all patients. RESULTS: Median
      operating theatre time was five hours and median blood loss was 1500 mL (60 mL-25
      L). Eighty percent of resections entailed four or more liver segments.
      Postoperative morbidity occurred in 26 (37.1%) and 30-day mortality was 5.7%.
      Median hospital stay was 11 days (2-67). In the 53 patients who underwent
      resection alone, the three and five-year actuarial survival rates, including the
      30-day mortality, were 62.0% and 27.2%, respectively. Dukes stage of the primary
      was the only significant prognostic factor found in this subgroup of patients
      (p<0.05). CONCLUSIONS: Resection of colorectal liver metastases can achieve
      extension of life and long-term survival in selected patients. However, it
      remains a major undertaking and is probably best performed in units with
      appropriate expertise and experience.

PMID- 10210295
TI  - Delay of catch-up growth in very low birthweight infants.
AB  - AIM: To determine if appropriate for gestational age, very low birth weight
      infants demonstrate catch-up growth. METHODS: The notes of 74 appropriate for
      gestational age, very low birth weight infants were reviewed and anthropometric
      measures converted into standard deviation scores (Z-scores). The growth of
      "well" infants was compared with that of "unwell" infants (those who developed
      necrotising enterocolitis, bronchopulmonary dysplasia or were not feeding at one
      week of age). RESULTS: All infants showed reduced weight (p<0.001) and head
      circumference (p<0.01) Z-scores at one week of age. This persisted until 35 weeks
      postmenstrual age in both groups, by which time length Z-scores had also reduced.
      The well group had regained birth Z-scores for all measurements by three months
      post-term. However the unwell group still had significantly lower weight (p<0.01)
      and length (p<0.05) Z-scores at three months. CONCLUSIONS: Well very low birth
      weight infants regained their birth percentiles by three months post-term. In
      infants with significant neonatal illness, this recovery was delayed.

PMID- 10210296
TI  - The health and health practices of doctors and their families.
AB  - AIM: To determine how practising doctors care for themselves and their families.
      METHOD: A questionnaire was submitted to 500 randomly selected doctors, seeking
      information on attitudes to diet, alcohol, smoking, screening, immunisation,
      contraception, workload, stress and treatment of self and family. RESULTS: Many
      doctors claimed to have a family doctor but relatively few had regular
      assessments. Most doctors considered their health to be good but many claimed to
      be working under substantial stress. There is need for more information about the
      Doctors' Health Advisory Service. CONCLUSION: Doctors should pay more attention
      to their own health. A good case can be made for doctors having regular check-ups
      performed by a respected general practitioner colleague.

PMID- 10210297
TI  - Systemic vasculitis associated with long-term phenytoin therapy.

PMID- 10210298
TI  - Tobacco control in New Zealand from 1945 to 1961.
AB  - The 1945 to 1961 period was characterised by a significant increase in the
      international scientific knowledge of the health risks of smoking. Despite this,
      there was relatively little response by the New Zealand Government, the New
      Zealand medical profession and other local agencies. Specific tobacco control
      activities were virtually limited to some episodic and low profile publicity
      measures, and an incidental increase in tobacco taxation. This limited response
      may have partly been due to the slow diffusion of the health risk information to
      health professionals in this country and the presence of other more obvious
      health concerns (such as polio epidemics). Other reasons may have been the
      absence of a New Zealand research base, the lack of focused advocacy groups,
      political wariness about using tobacco taxation, a minimalist approach by
      government to product safety regulation and the major extent to which smoking was
      normalised within New Zealand society. Britain and the US led to further
      research. Reports linking lung cancer to smoking were published in 1950 by Doll
      and Hill in Britain, and by Wynder and Graham in the US. As a result of
      subsequent prospective studies, the American Cancer Society and the British
      Medical Research Council produced in 1954, independent reports that death rates
      were higher for cigarette smokers. A number of further studies on smoking and
      health were published in Britain and the US during the 1950s (e.g. by Doll and
      Hill in 1954), and the Medical Research Council and the United States Surgeon
      General gave further strong warnings. However, the unease of some parts of the
      medical world with the new science of epidemiology was reflected in the confusion
      by public and politicians over the conclusiveness of the evidence. Nevertheless,
      by the late 1950s there was evidence of declining tobacco consumption amongst US
      doctors, partly at least because of concern about health risks such as lung
      cancer.

PMID- 10210299
TI  - Alternative medicine.

PMID- 10210300
TI  - Mirtazapine and the granulocytes--so far so good.

PMID- 10210301
TI  - Attempts to detect parasitic causes of diarrhoea.

PMID- 10210302
TI  - The outcome for patients with ME in New Zealand.

PMID- 10210303
TI  - Vancomycin resistant enterococci in New Zealand.

PMID- 10210304
TI  - A case of malaria.

PMID- 10210305
TI  - Interpretation of ANCA serology.

PMID- 10210306
TI  - Valuing quality of life: results for New Zealand health professionals.
AB  - AIMS: To illustrate the means by which health state preferences, which are
      required in the calculation of QALYs, may be generated. To elicit health state
      values from a sample of New Zealand health professionals, and to compare these
      with those evident from a sample of health professionals and of the general
      population overseas. METHODS: This research employed a questionnaire (EQ-5D)
      developed by the EuroQol group which elicits preferences for health states
      described in terms of three levels within each of five dimensions of health
      related quality of life. This questionnaire was administered to groups of
      students enrolled in a postgraduate Diploma of Public Health course in Auckland
      (1993-1995), Wellington and Dunedin (1993-1998), and Christchurch (1993-1997).
      RESULTS: The health state preferences for the New Zealand sample are similar to
      those evident for samples of health professionals in Sweden and, to a lesser
      extent, those evident from a sample of the English general public. CONCLUSIONS:
      The EQ-5D represents a means of readily eliciting health state preferences in the
      form required to facilitate cost utility analysis. Further research is required
      in New Zealand to generate a "tariff of health state preferences from the general
      public across all health states and to explore hypotheses specific to New
      Zealand, including the possibility that there may be significant differences
      between Maori and non-Maori with regards to health state preferences.

PMID- 10210307
TI  - Management of stroke in Auckland Hospital in 1996.
AB  - AIMS: To review the management of stroke in Auckland Hospital; compare current
      management with practice in Auckland in 1991/92; and determine how many patients
      may be suitable for treatment with aspirin or tissue plasminogen activator (t
      PA). METHODS: Retrospective review of case notes for all patients over the age of
      15 years presenting during four months in 1996 with symptoms and signs of an
      acute stroke. Subarachnoid haemorrhages were excluded. RESULTS: There were 184
      stroke events (135 ischaemic strokes, 26 intracerebral haemorrhages, 23
      unspecified strokes) in 179 patients. The time between the onset of symptoms and
      arrival in hospital was available for 109 patients: the overall median time was
      three hours, two hours for intracerebral haemorrhages, three hours for ischaemic
      strokes, four hours for unspecified strokes. Most patients (78%) were admitted to
      a general medical ward. Only 10% of the patients managed on a non-neurological
      ward were referred to a neurologist. Computed tomography (CT) was obtained in 88%
      of the patients. The median time from the onset of symptoms to CT was 19 hours
      (11 hours for intracerebral haemorrhages, 21 hours for ischaemic strokes). Only
      11 patients (10%) were scanned within three hours of the onset of symptoms. Of
      the 135 patients who had an ischaemic stroke, 36% were treated with aspirin and
      6% with heparin in the first 48 hours. Thirty-two patients (17%) died in
      hospital, 87 (47%) returned home, 37 (20%) were transferred to a rest home or
      private hospital and 28 (15%) were transferred to other places. CONCLUSIONS:
      Compared with 1991, the rate of CT scanning after a stroke increased from 42% to
      88%. At present, no more than 5% of all patients presenting with a stroke are
      suitable for consideration of treatment with t-PA. Routine treatment with aspirin
      in the first 48 hours could be achieved without other major changes in
      management.

PMID- 10210308
TI  - Antibiotic susceptibility of Streptococcus pneumoniae in New Zealand.
AB  - AIMS: To determine the current antibiotic susceptibility patterns of
      Streptococcus pneumoniae from four centres in New Zealand. METHODS: Over a six
      month period in 1997, 386 consecutive clinical isolates of S pneumoniae were
      collected by four laboratories (Auckland, Wellington, Hamilton and Christchurch)
      from general practice or inpatients. Susceptibility testing for seven antibiotics
      was performed by each centre using the Etest. RESULTS: Eighty-three-percent of
      isolates were penicillin susceptible, 12% showed intermediate resistance to
      penicillin and 5% were penicillin resistant. Overall, 93 and 91% of isolates were
      susceptible to amoxicillin/clavulanic acid and ceftriaxone, respectively.
      Erythromycin and tetracycline had similar rates of susceptibility (88 and 87%,
      respectively). Resistance to cotrimoxazole was common, with only 57% of isolates
      susceptible to this combination. No National Committee for Clinical Laboratory
      Standard (NCCLS) breakpoints were available for cefaclor to allow interpretation
      of the minimum inhibitory concentration data for this agent. Wellington had lower
      resistance rates than Auckland, Christchurch and Hamilton. Isolates from children
      had consistently higher resistance rates (two- to five-fold greater for beta
      lactams and 1.2 to 1.3-fold for other agents) compared with isolates from adult
      patients. CONCLUSIONS: Resistance to multiple antibiotics among S pneumoniae is
      now evident in New Zealand, although rates varied between study centres. The
      overall rate of penicillin resistance is 5%, which is similar to that observed in
      many European and US cities but lower than the rates reported in badly affected
      areas (> 30%). These data suggest that amoxicillin (+/- clavulanic acid),
      erythromycin or tetracycline are appropriate agents for empirical use in less
      serious community acquired infections when S pneumoniae is suspected.
      Ceftriaxone, with or without vancomycin, should be considered in the empirical
      treatment of invasive, disease until sensitivities are known.

PMID- 10210309
TI  - An unusual cause of haematuria.
AB  - A case of gross haematuria is described in a young woman. This was initially
      attributed to the use of analgesics. Subsequent history and investigation
      confirmed that the cause for the haematuria was sickle cell trait occurring in an
      individual in whom it was not initially suspected.

PMID- 10210311
TI  - ME versus CFS.

PMID- 10210310
TI  - Occupational health practice in New Zealand.
AB  - On the basis of the national un-funded liability for work injuries and illnesses,
      and comparisons of health outcome and cost data to a benchmark, it can be
      concluded that occupational health practice in New Zealand is deficient. This
      deficiency persists despite recent legislative reforms and is due to a
      combination of Accident Rehabilitation and Compensation Insurance Corporation,
      health professional and industrial factors. It is clear that a comprehensive
      corrective strategy is needed to attend to: the up-skilling of health case
      managers and the medical profession in concert; and, to encouraging employers to
      introduce comprehensive occupational health programmes.

PMID- 10210312
TI  - Maximising the detection of bacterial enteric pathogens.

PMID- 10210313
TI  - Truffles or earthballs?

PMID- 10210314
TI  - Visual hallucinations after quinapril.

PMID- 10210315
TI  - Cytoskeleton and integrin-mediated adhesion signaling in human CD34+ hemopoietic
      progenitor cells.
AB  - Significant progress has been made recently in the understanding of cell adhesion
      signaling. Many components of focal adhesion complexes have been identified in
      fibroblasts and endothelial cells, showing considerable overlap and
      complementarity between growth signaling mediated by growth factor receptors and
      adhesive signaling mediated by cell adhesion receptors such as integrins. These
      studies showed that the cytoskeleton is essential for the correct intracellular
      localization of large signaling complexes that regulate the cellular machinery.
      Although adhesive interactions are essential to maintain steady-state
      hemopoiesis, the study of the function and role of adhesive interactions in
      hemopoietic progenitor and stem cells is less advanced. As in fibroblasts,
      functional overlap between hemopoietic growth factor receptors and cell adhesion
      receptors has been demonstrated, with the cytoskeleton likely playing a critical
      role in integrating information provided by soluble factors and cell adhesion
      molecules constituting the hemopoietic microenvironment. The intention of this
      article is to give a critical review of the current knowledge about the
      cytoskeleton and integrin-mediated signaling in hemopoietic progenitor cells.

PMID- 10210316
TI  - A patient-derived mutant form of the Fanconi anemia protein, FANCA, is defective
      in nuclear accumulation.
AB  - Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome with
      at least eight complementation groups (A-H). Three FA genes, corresponding to
      complementation groups A, C, and G, have been cloned, but the function of the
      encoded FA proteins remains unknown. We recently demonstrated that the FANCA and
      FANCC proteins bind and form a nuclear complex. In the current study, we
      identified a homozygous mutation in the FANCA gene (3329A>C) in an Egyptian FA
      patient from a consanguineous family. This mutant FANCA allele is predicted to
      encode a mutant FANCA protein, FANCA(H1110P), in which histidine 1110 is changed
      to proline. Initially, we characterized the FANCA(H1110P) protein, expressed in
      an Epstein Barr virus (EBV)-immortalized lymphoblast line derived from the
      patient. Unlike wild-type FANCA protein expressed in normal lymphoblasts,
      FANCA(H1110P) was not phosphorylated and failed to bind to FANCC. To test
      directly the effect of this mutation on FANCA function, we used retroviral
      mediated transduction to express either wild-type FANCA or FANCA(H1110P) protein
      in the FA-A fibroblast line, GM6914. Unlike wild-type FANCA, the mutant protein
      failed to complement the mitomycin C sensitivity of these cells. In addition, the
      FANCA(H1110P) protein was defective in nuclear accumulation in the transduced
      cells. The characteristics of this mutant protein underscore the importance of
      FANCA phosphorylation, FANCA/FANCC binding, and nuclear accumulation in the
      function of the FA pathway.

PMID- 10210318
TI  - Transforming growth factor beta inhibits growth of more differentiated myeloid
      leukemia cells and retinoblastoma protein phosphorylation at serine 795.
AB  - Transforming growth factor beta (TGF-beta) has been shown to be a specific
      inhibitor of early human myeloid progenitors. We show here that TGF-beta1
      potentially inhibited not only the growth of primitive but also more mature
      myeloid leukemic cells. Surprisingly, those apparently more mature progenitor
      cells, such as MV4-11 and Mo7e cells, are very sensitive to the action of TGF
      beta. The addition of TGF-beta1 to liquid cultures of these cells significantly
      inhibited their proliferation, with as much as 72% inhibition of growth of MV4-11
      cells. The suppressive effect by TGF-beta1 was not reversed or prevented by
      granulocyte-macrophage colony-stimulating factor or interleukin 3 used to promote
      cell growth in TF-1a and MV4-11 cells. TGF-beta1 completely abolished the clonal
      growth of MV4-11 cells in soft agar and inhibited Mo7e, KG-1, K562, TF-1, and TF
      1a colony growth by 99%, 90%, 63%, 53%, and 43%, respectively. The cells treated
      with TGF-beta1 showed progressive accumulation in the G1 phase of cell cycle.
      Maximal G1 arrest (93%) was observed in MV4-11 cells. Using anti-retinoblastoma
      protein (pRb) and anti-specific phosphorylated-pRb antibodies, we demonstrated
      that TGF-beta1 greatly inhibited pRb phosphorylation at serine 795 in MV4-11 and
      Mo7e cells. Taken together, our data suggest that the sensitivity of myeloid
      leukemic progenitor cells to growth inhibition by TGF-beta may not be inversely
      correlated with their maturation stage, and the inhibition of the cells appeared
      to be linked to the suppression of pRb phosphorylation at serine 795.

PMID- 10210317
TI  - Ectopic expression of the Aspergillus nidulans mitotic inducer, nimA kinase, in
      megakaryocytes: effect on polyploidization.
AB  - Aspergillus nidulans nimA gene encodes a serine/threonine protein kinase (NIMA)
      whose activity is essential for mitotic entry and chromatin condensation. Both
      the activity and the abundance of NIMA protein increase at the G2/M transition of
      the fungal cell cycle. In this study, we report the effects elicited by ectopic
      expression of nimA on polyploidization in a mouse megakaryocytic line, Y10, which
      is undergoing an endomitotic cell cycle. A pool of Y10 stable transfectants that
      have been induced to express nimA displayed a decrease in cell number and an
      elevated DNA content per cell. NIMA also dramatically enhanced the activity of
      phorbal 12-myristate 13-acetate toward polyploidization. Analysis of individual
      nimA transfectants revealed that the DNA content per cell rose in cells
      expressing high levels of nimA and that the level of cyclin B was reduced as
      compared to the mock-transfected cells. These effects observed in polyploidizing
      megakaryocytes are in contrast to those found in A. nidulans and HeLa cells, in
      which induced nimA expression caused abnormal chromatin condensation and cell
      cycle arrest. We conclude that high-level expression of nimA in cells programmed
      to undergo endomitosis could potentiate polyploidization. The challenge now
      resides in the isolation of the authentic megakaryocyte counterpart of the fungal
      nimA.

PMID- 10210319
TI  - Ex-vivo expansion of bone marrow progenitor cells for hematopoietic
      reconstitution following high-dose chemotherapy for breast cancer.
AB  - The use of hematopoietic growth factors, stromal monolayers, and frequent medium
      exchange allows the expansion of hematopoietic progenitors ex-vivo. We evaluated
      the use of ex-vivo expanded progenitor cells for hematopoietic reconstitution
      following high dose chemotherapy (HDC) in breast cancer patients. Patients with
      high-risk Stage II or metastatic breast carcinoma underwent bone marrow
      aspirations using general anesthesia. A total of 675-1125 x 10(6) mononuclear
      cells (MNC) were seeded for ex-vivo expansion for 12 days in controlled perfusion
      bioreactors (Aastrom Biosciences, Inc.). The bone marrow cultures, which included
      the stromal cells collected with the aspirate, were supplemented with
      erythropoietin, granulocyte-macrophage-colony stimulating factor (GM-CSF)/IL-3
      fusion protein (PIXY 321), and flt3 ligand. Stem cell transplant was performed
      with expanded cells after HDC. A median bone marrow volume of 52.9 mL (range 42
      187 mL) was needed to inoculate the bioreactors. Median fold expansion of
      nucleated cells (NC) and colony forming unit granulocyte-macrophage (CFU-GM) was
      4.9 and 9.5, respectively. The median fold expansion of CD34+lin- and long-term
      culture-initiating culture (LTC-IC) was 0.42 and 0.32, respectively. Five
      patients were transplanted with ex-vivo expanded NC. Median days to an absolute
      neutrophil count > 500/microL was 18 (range 15-22). Median days to a platelet
      count > 20,000/microl was 23 (range 19-39). All patients had sustained
      engraftment of both neutrophils and platelets. Immune reconstitution was similar
      to that seen after HDC and conventional stem cell transplantation. We conclude
      that ex-vivo expansion of progenitor cells from perfusion cultures of small
      volume bone marrow aspirates, allows hematopoietic reconstitution after HDC.

PMID- 10210320
TI  - Prospective identification of erythroid elements in cultured peripheral blood.
AB  - We have developed a prospective approach to identify the generation of erythroid
      cells derived from cultured peripheral blood mononuclear cells (PBMC) by
      monitoring the expression of the cell surface protein CD48. Unpurified
      populations of PBMC obtained from the buffy coats of normal volunteers were grown
      in suspension culture in the absence or presence of erythropoietin. A profile of
      surface CD48 expression permitted a flow cytometric identification of
      erythropoietin responsive populations at various stages of their maturation. In
      the absence of erythropoietin (EPO) supplemented media, the CD48- cells
      represented <5% of the total population of PBMC remaining in culture. In cultures
      supplemented with 1 U/mL EPO, the mean percentage of CD48- cells increased to
      34.7 + 14.9% (p < 0.01) after 14 days in culture. Coordinated CD34 and CD71
      (transferrin receptor) expression, morphology, gamma-globin transcription, and
      colony formation in methylcellulose were observed during the 14-day culture
      period. Flow cytometric monitoring of bulk cultured PBMC provides a simple and
      reliable means for the prospective or real-time study of human erythropoiesis.

PMID- 10210321
TI  - Unexpected and coordinated expression of Spi-1, Fli-1, and megakaryocytic genes
      in four Epo-dependent cell lines established from transgenic mice displaying
      erythroid-specific expression of a thermosensitive SV40 T antigen.
AB  - Most erythroleukemic cell lines established in vitro coexpress erythrocytic and
      megakaryocytic markers that often are associated with expression of Spi-1 and/or
      Fli-1 transcription factors known as transactivators of megakaryocyte-specific
      promoters. In the present study, we examined the possibility of establishing new
      cell lines keeping strictly erythroid-specific properties in vitro through the
      targeted and conditional immortalization of erythrocytic progenitors. For that
      purpose, we established several lines of transgenic mice displaying erythroid
      specific expression of a thermosensitive SV40 T antigen. As expected, these
      transgenic mice developed splenomegaly due to the massive amplification of Ter
      119 positive erythroid nucleated cells expressing T antigen. Despite this drastic
      effect in vivo, the in vitro immortalization of erythropoietin-dependent
      erythroid progenitors unexpectedly occurred at low frequency, and all four cell
      lines established expressed both erythrocytic (globins) and megakaryocytic
      markers (glycoprotein IIb, platelet factor 4) as well as Spi-1 and Fli-1
      transcripts at permissive temperature. Switching the cells to the nonpermissive
      temperature led to a marked increase in globin gene expression and concomitant
      decrease in expression of Spi-1, Fli-1, and megakaryocytic genes in an
      erythropoietin-dependent manner. Interestingly, enhanced expression of Spi-1 and
      Fli-1 genes already was detected in the Ter 119 positive cell population of
      transgenic mice spleen in vivo. However, like normal Ter 119 erythroid cells,
      these Ter 119 positive cells from transgenic mice still expressed high levels of
      beta-globin and very low or undetectable glycoprotein IIb and platelet factor 4
      megakaryocytic transcripts. Taken together, these data indicate that the
      unexpected expression of megakaryocytic genes is a specific property of
      immortalized cells that cannot be explained only by enhanced expression of Spi-1
      and/or Fli-1 genes.

PMID- 10210322
TI  - Retinoic acid induces apoptosis of human CD34+ hematopoietic progenitor cells:
      involvement of retinoic acid receptors and retinoid X receptors depends on
      lineage commitment of the hematopoietic progenitor cells.
AB  - Retinoids are bifunctional regulators of growth and differentiation of
      hematopoietic cells. In this study we explored the effects of retinoic acid (RA)
      on apoptosis of human CD34+ hematopoietic progenitor cells isolated from normal
      bone marrow. RA (100 nM) induced an increase in the percentage of dead cells from
      24% to 44% at day 6 (p < 0.05, n = 6) as compared to control cells cultured in
      medium alone. The effect was dose dependent and appeared relatively late.
      Significant differences were observed from day 4 onward. Apoptosis, or programmed
      cell death, was demonstrated as the mode of cell death by using the TUNEL assay,
      which detects single strand nicks in DNA, or by the Nicoletti technique
      demonstrating a subdiploid population by DNA staining. RA previously was found to
      inhibit granulocyte colony-stimulating factor--and not granulocyte-macrophage
      colony-stimulating factor--stimulated proliferation of CD34+ cells. However, we
      found that RA opposed anti-apoptotic effects of G-CSF and GM-CSF on CD34+ cells
      (G-CSF: 8% dead cells at day 6; G-CSF + RA: 20%; GM-CSF: 12%; GM-CSF + RA: 27%).
      Moreover, RA induced apoptosis of CD34+ cells and CD34+CD71+ cells stimulated
      with erythropoietin. To explore the receptor signaling pathways involved in RA
      induced apoptosis, we used selective ligands for retinoic acid receptors (RARs;
      RO13-7410) and retinoid X receptors (RXRs; RO 25-6603). We found that RARs were
      involved in RA-mediated apoptosis of myeloid progenitor cells, whereas RARs as
      well as RXRs were involved in RA-mediated apoptosis of erythroid progenitor
      cells.

PMID- 10210323
TI  - Stem cell factor and interleukin-4 induce murine bone marrow cells to develop
      into mast cells with connective tissue type characteristics in vitro.
AB  - In this study, we have developed a method to obtain mast cells with connective
      tissue type mast cell (CTMC) characteristics directly from mouse bone marrow (BM)
      cells. BM cells were grown for 3 weeks in presence of interleukin-4 (IL-4) plus
      stem cell factor (SCF). SCF alone poorly supported growth and development of mast
      cells. IL-4 dose-dependently enhanced the expression of c-kit and high-affinity
      receptor for IgE (Fc(epsilon)RI) on the cell surface of SCF-cultured BM cells.
      Furthermore, cytoplasmic granulation and histamine synthesis of BM-derived mast
      cells were increased in presence of IL-4 and SCF. Histochemical staining
      demonstrated that granules were safranin positive. BM-derived mast cells could be
      activated for granule exocytosis (beta-hexosaminidase release) and lipid mediator
      generation (LTC4 production) via Fc(epsilon)RI after sensitization with IgE and
      subsequent crosslinking with multivalent antigen. In addition, mast cells derived
      from BM cells cultured with SCF plus IL-4 could be activated by substance P, a
      nonimmunologic stimulus, to release beta-hexosaminidase. The results presented
      indicate that IL-4 and SCF both have a prominent role in the development of mast
      cells from murine BM cells in vitro. Mast cells can directly be derived from BM
      cells in presence of SCF and IL-4 and the cultured cells show typical hallmarks
      of CTMC, indicating that precursor cells for CTMC may be present in BM. The
      described culture procedure may be useful to investigate the molecular aspects of
      the development of committed mast cell lineages.

PMID- 10210324
TI  - Flt3 ligand can promote survival and macrophage development without proliferation
      in myeloid progenitor cells.
AB  - Flt3 ligand elicits a variety of effects on early hemopoietic progenitors by
      occupying its cognate receptor, Flt3, a member of the type III tyrosine kinase
      receptor family. The cytokines macrophage colony-stimulating factor (M-CSF) and
      stem cell factor (SCF) bind to related members of this tyrosine kinase receptors
      family, c-fms and c-kit, respectively. The relative effects of the cytokines M
      CSF, SCF, and Flt3L on the proliferation and development of the late myeloid
      progenitors granulocyte-macrophage colony-forming cells (GM-CFC) were
      investigated. Distinct biologic responses were stimulated by ligand binding to
      these different tyrosine kinase receptors in enriched GM-CFC. M-CSF stimulated GM
      CFC to proliferate and develop into macrophages. SCF, on the other hand,
      stimulated GM-CFC to develop into neutrophils. Flt3 ligand had a relatively small
      proliferative effect on enriched GM-CFC compared to SCF and M-CSF and had no
      ability to either stimulate colony formation or synergize with these two
      cytokines in promoting DNA synthesis, colony formation, or expansion in liquid
      culture. Flt3 ligand, however, was capable of maintaining the clonogenic
      potential of GM-CFC and acted as an anti-apoptotic agent as assessed using the
      Annexin-V apoptosis assay. GM-CFC cultured in Flt3 ligand eventually formed
      macrophages and neutrophils in liquid culture. Labeling with the membrane
      associated cell tracker dye PKH26 indicated that the majority of the enriched GM
      CFC responded to Flt3 ligand by undergoing limited proliferation and macrophage
      development, whereas other cells survived but did not proliferate and
      differentiate into macrophages. Thus, Flt3 ligand promoted survival and
      stimulated development without proliferation in primary-enriched myeloid
      progenitor cells.

PMID- 10210325
TI  - Detection of residual disease in pediatric B-cell precursor acute lymphoblastic
      leukemia by comparative phenotype mapping: a study of five cases controlled by
      genetic methods.
AB  - We recently investigated samples of pediatric B-cell precursor acute
      lymphoblastic leukemia (BCP-ALL) and normal bone marrow (BM). We found that
      leukemic blasts, compared to their physiologic counterpart cells, frequently
      display aberrant phenotypes with respect to levels of expression of certain
      antigens. Using multiparameter flow cytometry, these differences enabled us to
      trace leukemic cells admixed to normal BM, which suggested that this approach
      might be a useful strategy for minimal residual disease detection. In the present
      study, we used the same multiparameter approach ("comparative phenotype mapping")
      to prove that such quantitative phenotypic differences really exist between
      malignant and normal BCP when simultaneously present in the BM. We demonstrate
      this by five exemplary follow-up BM samples from patients with BCP-ALL, all of
      which showed phenotypically aberrant cells according to levels of expression of
      CD10, CD11a, CD19, CD34, CD44, or CD45RA, as well as according to altered
      orthogonal light scattering properties. We confirmed the leukemic nature of these
      cells by polymerase chain reaction-based detection of bcr1/abl transcripts, and
      of leukemia clone-specific immunoglobulin heavy chain rearrangements in only the
      suspicious cells when sorted by flow cytometry, but not in normal BCP or non-B
      cells. Comparative phenotype mapping thus allows one to distinguish between
      normal and leukemic cells, and we show that it may enable rapid, specific, and
      quantitative detection of residual/resurgent leukemia in BCP-ALL.

PMID- 10210326
TI  - Establishment and characterization of a mouse strain (TLL) that spontaneously
      develops T-cell lymphomas/leukemia.
AB  - In this study, a mouse strain (TLL) that spontaneously develops T-cell
      lymphomas/leukemia with an early onset and high incidence was established and
      characterized. All tumors analyzed were found to express the alpha,beta T-cell
      receptor, and the majority of them had a mature, CD3+CD4+CD8- immunophenotype. In
      a few cases, tumors with a more immature CD3+CD4+CD8+ phenotype were isolated.
      Expanded phenotyping using a broad panel of lymphocyte differentiation markers
      confirmed the mature T-cell phenotype of the tumors. Histologic and cell cycle
      analysis of the tumors revealed an aggressive lymphoblastic malignancy with a
      very high proliferation rate and widespread engagement of bone marrow and
      lymphoid as well as nonlymphoid organs. Thus, the TLL mouse strain represents a
      unique model for the analysis of the oncogenesis and progression of mature T-cell
      tumors and for the development of therapeutic measures to combat such tumors.

PMID- 10210327
TI  - Spontaneous canine mast cell tumors express tandem duplications in the proto
      oncogene c-kit.
AB  - Spontaneous mast cell tumors (MCT) are the most common malignant neoplasm in the
      dog, representing between 7% and 21% of all canine tumors, an incidence much
      higher than that found in humans. These tumors often behave in an aggressive
      manner, metastasizing to local lymph nodes, liver, spleen, and bone marrow. The
      proto-oncogene c-kit is known to play a critical role in the development and
      function of mast cells. Point mutations in the kinase domain of c-kit leading to
      tyrosine phosphorylation in the absence of ligand binding have been identified in
      three mastocytoma lines, (P815, RBL, and HMC-1), and some human patients with
      various forms of mastocytosis. We now demonstrate that although c-kit derived
      from canine MCT did not contain the previously described activating point
      mutations, 5 of the 11 tumors analyzed possessed novel mutations consisting of
      tandem duplications involving exons 11 and 12. We also show that one such
      duplication, detected in a canine mastocytoma cell line, was associated with
      constitutive phosphorylation of c-kit protein (KIT), suggesting that these
      mutations may contribute to the development or progression of canine MCT.

PMID- 10210328
TI  - Involvement of CD44 variant isoform v10 in progenitor cell adhesion and
      maturation.
AB  - CD44 has been described repeatedly to be involved in hematopoiesis. Here, we
      addressed the question of functional activity of CD44 variant isoform v10
      (CD44v10) in progenitor cell maturation by in vivo and in vitro blocking studies
      with a monoclonal antibody and a receptor globulin. We became interested in this
      question by the observation that CD44v10 is expressed, although at a low level,
      on a subpopulation of bone marrow cells. Flow cytometry revealed that 15%-20% of
      hematopoietic cells in the fetal liver and 25%-35% of bone marrow cells in adult
      mice were CD44v10 positive. The majority of CD44v10+ cells was HSA+/J11d+ and
      CD43+. CD44v10 was not detected on CD4+, CD8+, IgM+, or IgD+ cells. A CD44v10
      receptor globulin did not bind to hematopoietic progenitor cells, but to stromal
      elements. The CD44v10-CD44v10 ligand interaction had a major impact on the
      adhesion of progenitor cells to stromal elements. When healthy animals received
      repeated injections of either anti CD44v10 or the CD44v10 receptor globulin,
      committed progenitors were mobilized and significantly augmented numbers were
      recovered in the spleen and the peripheral blood. Furthermore, the CD44v10
      CD44v10 ligand interaction, which had no impact on progenitor expansion,
      influenced progenitor maturation, particularly of the B-cell lineage. Although
      the nature of the CD44v10 ligand remains to be explored, the supportive role of
      CD44v10 in progenitor maturation and, importantly, the efficient mobilization of
      progenitor cells by anti-CD44v10 and a CD44v10 receptor globulin could be of
      clinical benefit in peripheral blood stem cell transplantation.

PMID- 10210329
TI  - Oncostatin M transforms lymphoid tissue function in transgenic mice by
      stimulating lymph node T-cell development and thymus autoantibody production.
AB  - Oncostatin M (OM) is a member of the IL-6 subfamily of cytokines that is
      expressed in primary lymphoid tissues such as bone marrow and thymus, as well as
      in secondary lymphoid tissues and activated leukocytes. We produced transgenic
      mice that overexpressed the human, bovine, or mouse OM genes and compared their
      relative ability to modulate lymphopoiesis. Each species of cytokine induced a
      similar extrathymic pathway of T-cell development involving the accumulation of
      immature T cells within lymph nodes. Reconstitution experiments utilizing
      lethally irradiated athymic mice indicated that OM had caused hematopoietic
      precursors within fetal liver and bone marrow to initiate lymph node T-cell
      development in the absence of a thymic environment. Breeding experiments with IL6
      /- and IL-7r(alpha)-/- deficient mice, indicated that induction of this
      extrathymic pathway by the OM transgene occurred in the absence of IL-6, but was
      strictly dependent on IL-7 receptor signaling. Separately, OM stimulated the
      accumulation of immature B cells within the transgenic thymus and caused the
      subcapsular regions of the thymus to expand with mature B and T cells. This
      thymus conversion to secondary lymphoid tissue was responsible for a lethal
      autoimmune-like disease marked by high titers of circulating autoantibodies,
      proteinuria, and glomerulonephritis. The conserved phenotypes elicited by these
      three forms of OM indicate that this potent hematopoietic cytokine can regulate
      lymphoid tissue function and morphogenesis.

PMID- 10210330
TI  - NK cell colony formation from human fetal thymocytes.
AB  - We established a clonal cell culture system for human natural killer (NK) cells
      from fetal thymocytes. Thymocytes of 16 to 22 gestational weeks were cultured in
      methylcellulose in the presence of interleukin (IL)-7, IL-15, and steel factor
      (SF). After 14 days in incubation, large, diffuse colonies consisting of small
      cells were identified. Cells in the colonies were medium- to large-sized granular
      lymphocytes, expressing CD56 but not CD3, and revealed lytic activity against
      K562 cells. Colony-forming units (CFU)-NK were enriched in lineage negative (Lin-
      ) CD34++ subpopulations of fetal thymocytes, whereas a smaller number of CFU-NK
      also existed in Lin-CD34+ and Lin-CD34- subpopulations. Cytokine requirement for
      the NK cell colony formation was examined under serum-free conditions. As a
      single agent, only IL-15, but not IL-2, IL-7, or SF, supported NK cell colony
      formation. IL-15 had synergy with IL-7 and SF independently, and the maximal
      number of colonies were obtained when the three cytokines were present. IL-2 also
      supported NK cell colony formation in the presence of SF. When IL-2 was added to
      cultures containing IL-15 alone, IL-15 plus SF, or IL-15, SF, and IL-7, the
      numbers of NK cell colonies were reduced relative to those without IL-2. These
      results indicate that IL-2 may regulate IL-15-responsive NK cell progenitors.
      This clonal culture system will be a useful tool in the investigation of NK cell
      ontogeny.

PMID- 10210331
TI  - Direct contact between CD34+lin- cells and stroma induces a soluble activity that
      specifically increases primitive hematopoietic cell production.
AB  - Perfused human bone marrow (BM) mononuclear cell (MNC) cultures result in a
      greater long-term culture-initiating cell (LTC-IC) output than parallel CD34+lin-
      cell cultures, even when CD34+lin- cells are placed on irradiated preformed
      stroma (IPFS). This difference has been attributed to accessory cell effects that
      are potentiated by medium perfusion. The present study investigated the relative
      contributions of direct contact- and soluble-mediated mechanisms of accessory
      cells in this culture system. CD34+lin- cells within (i.e., in contact with) the
      MNC accessory cell mixture generated greater LTC-IC output than CD34+lin- cells
      in contact with IPFS. Incubation of CD34+lin- cells with MNC conditioned medium
      (CM) resulted in partial restoration of MNC accessory activity, while CM from
      IPFS had no activity on LTC-IC output. Interestingly, the level of LTC-IC output
      supported by MNC CM was equivalent to that supported by direct contact with IPFS.
      CD34+lin- cells were then cultured in Transwell inserts either alone, with IPFS
      (direct contact), or with IPFS below the insert. Direct contact with IPFS
      significantly increased the output of cells, CFU-GM, and LTC-IC from CD34+lin-
      cells. IPFS below the insert also resulted in significantly increased cell and
      CFU-GM output, but did not significantly affect LTC-IC output. Further
      experiments using CM from CD34+lin- cells and IPFS cultures showed that LTC-IC
      supportive activity was present only when direct contact was allowed between
      CD34+lin- cells and IPFS. ELISA and RT-PCR experiments showed that contact did
      not induce changes in the levels of several known growth factors, including GM
      CSF, IL-1beta, IL-3, IL-6, IL-11, LIF, KL, FL, Tpo, TGF-beta, and MIP-1alpha.
      These results indicate that direct contact between CD34+lin- cells and IPFS
      induces soluble activity, which specifically increases LTC-IC output from
      CD34+lin- cell cultures, providing evidence for a novel direct contact-mediated
      two-way mechanism of communication between primitive hematopoietic cells and
      stroma.

PMID- 10210332
TI  - A homolog of the fungal nuclear migration gene nudC is involved in normal and
      malignant human hematopoiesis.
AB  - The filamentous fungus Aspergillus nidulans nudC gene has an essential function
      in movement of nuclei following mitosis and is required for normal colony growth.
      Here, the molecular cloning and role in hematopoiesis of a human gene (designated
      HnudC) homologous to A. nidulans nudC is reported. The amino terminus of the
      larger human protein (HNUDC = 45 kDa) does not overlap with A. nidulans NUDC (22
      kDa). However, NUDC and the C-terminal 94 amino acids of HNUDC are 67% identical.
      The C-terminal region of the HnudC gene fully complements the A. nidulans
      temperature-sensitive nudC3 mutation, suggesting that nudC has an essential
      function in cell growth that is conserved from filamentous fungi to humans. In
      initial studies, HNUDC levels were much higher in erythroid precursors compared
      to most other human tissues. Therefore, the potential role of HnudC in
      hematopoiesis was explored. In normal human bone marrow, HNUDC protein and mRNA
      are highly expressed in early myeloid and erythroid precursors and decline as
      these cells terminally differentiate. To determine whether hematopoietic growth
      factors induce HnudC expression, TF-1 cells were stimulated by granulocyte
      macrophage colony-stimulating factor. This induced a significant increase in
      HNUDC protein and HnudC mRNA, suggesting that enhancement of HnudC expression in
      response to growth factor stimulation may be mediated at the transcription level.
      Furthermore, HNUDC was significantly enhanced in lysates of bone marrow aspirates
      from patients with acute myelogenous and acute lymphoblastic leukemia compared to
      aspirates from normal controls, suggesting that HnudC is involved in malignant
      hematopoietic cell growth as well. These data demonstrate that HNUDC is highly
      expressed in normal and malignant human hematopoietic precursors and suggest it
      is of functional importance in the proliferation of these cells.

PMID- 10210333
TI  - Generation of phagocytic MAK and MAC-DC for therapeutic use: characterization and
      in vitro functional properties.
AB  - Phagocytic cells with macrophage or dendritic cell phenotype, able to capture and
      ingest tumor cells, were derived in large numbers from peripheral blood
      mononuclear cells using two different activation procedures. Peripheral blood
      mononuclear cells were stimulated in nonadherent conditions in the presence of
      human AB serum with either granulocyte-macrophage colony-stimulating factor and
      dihydroxy-vitamin D3 for 7 days and with interferon-gamma for the last 18 hours
      to obtain activated macrophages (MAK) or with granulocyte-macrophage colony
      stimulating factor and interleukin-13 for 7 days (with fresh interleukin-13 added
      on day 4) to obtain macrophage-dendritic cells (MAC-DC). A strong ability of MAC
      DC to phagocytose yeasts was observed, in contrast to a low-intermediate
      phagocytosis capacity by MAK. Both CD14+ FCgammaR+ (FcgammaRI/CD64,
      FcgammaRII/CD32, FcgammaRIII/CD16) MAK and CD1a+/CD86+, CD14- MAC-DC were able to
      phagocytose whole tumor cells. However, only MAK phagocytosis was enhanced by
      FcgammaR engagement. MAK but not MAC-DC could lyse tumor cell in antibody
      dependent cell cytotoxicity assays, via FcgammaRI. Thus, MAK as well as MAC-DC
      may represent valuable tools for different in vivo therapy strategies that do or
      do not include the use of monoclonal antibodies.

PMID- 10210334
TI  - Primitive human hematopoietic progenitor cells express receptors for granulocyte
      macrophage colony-stimulating factor.
AB  - Most cytokines act only synergistically in assays of primitive progenitor cell
      proliferation, and effects have usually been observed first after prolonged cell
      culture. Studies reporting that primitive progenitors lack receptors for a number
      of cytokines, including granulocyte-macrophage colony stimulating factor (GM
      CSF), could indicate that several "synergistic" cytokines primarily affect cells
      that have differentiated in vitro. Here, however, we show that freshly isolated
      primitive progenitor cells (CD34hi CD38-) express receptors for GM-CSF at levels
      20%-30% of granulo-monocytic progenitors. Although GM-CSF had minimal effects on
      the survival or proliferation of primitive progenitors when added alone, the
      cytokine enhanced stem cell factor (SCF) induced cell cycle entry in the first
      generation. The effect was not observed when cells were incubated sequentially
      with SCF and GM-CSF. The results suggest that the synergistic effects of GM-CSF
      are mediated directly on primitive progenitor cells and that the cytokine may be
      useful to enhance cell cycle entry of hematopoietic stem cells.

PMID- 10210335
TI  - Thoracic imaging.

PMID- 10210336
TI  - Radiology of intervertebral cages in spinal surgery.
AB  - This pictorial essay reviews the normal appearances and the post-operative
      complications of intervertebral cages. These are implants which are being more
      widely used in spinal surgery. The text outlines the background leading to their
      development, the clinical indications and surgical techniques for insertion of
      the cages. The normal post-operative appearance of fusion and the complications
      that can occur are emphasized.

PMID- 10210337
TI  - Imaging of the thorax in the management of germ cell testicular tumours.
AB  - AIM: To evaluate role of chest computed tomography (CTC) and chest radiography
      (CXR) in management of patients with testicular germ cell tumours (GCT). PATIENTS
      AND METHODS: An analysis was undertaken of staging and re-assessment CTC and CXR
      examinations performed on patients with GCT over a 4.5-year period. Data were
      obtained on clinical presentation, tumour histology, tumour marker levels and
      clinical course. Consensus review interpretation was combined with these data to
      obtain a 'standard of reference'. Sensitivity, specificity and predictive values
      were derived by comparison of original imaging reports to 'standard of
      reference'. RESULTS: Six hundred and twenty-three CTC examinations on 207
      patients with GCT were included. Intrathoracic metastases were identified in 1%
      of seminoma patients compared with 20% of non-seminoma (NSGCT) patients. CTC was
      more accurate than CXR in the detection of intrathoracic metastases at 0.97, 0.96
      0.98 (95% CI) compared with 0.91, 0.89-0.93. The agreement between imaging
      techniques and the standard of reference (determined by Kappa statistic) was
      respectively 0.96 for CTC and 0.65 for CXR. In GCT patients undergoing re
      assessment with both CXR and CTC, CXR never detected unknown intrathoracic
      metastatic disease. Abdominopelvic lymphadenopathy was associated with
      intrathoracic metastases (P < 0.001), however re-assessment CTC did identify
      intrathoracic metastases in 27 cases without concurrent abdominopelvic disease.
      CXR was negative in 19 of these. CONCLUSION: Routine interval CXRs are
      unnecessary in NSGCT patients undergoing regular re-assessment CTC due to the low
      additional yield and limited effect on management. Re-assessment should still
      include CTC. In low risk, pure seminoma patients (abdominal CT and marker
      negative) re-assessment CTC can be safely avoided. Baseline CTC is advocated with
      CXR alone for re-assessment.

PMID- 10210338
TI  - The cost effectiveness of metal oesophageal stenting in malignant disease
      compared with conventional therapy.
AB  - Expanding metal oesophageal stents are being used more commonly to palliate
      patients with inoperable oesophageal carcinoma. Many reports have so far
      documented their clinical effectiveness, however, their high acquisition cost has
      caused on-going concern when compared with the cost of conventional therapies. We
      reviewed 64 consecutive patients with inoperable oesophageal carcinoma, half of
      whom had received our conventional method of palliation using a variety of
      techniques including, BICAP diathermy, alcohol injection and Atkinson tube
      insertion. The other half (32 patients) were treated with expandable metal stents
      -- Gianturco Z stents (Cook UK Ltd) and uncovered Ultraflex stents (Microvasive,
      Boston Scientific). The physical amount of resources consumed were identified and
      measured (number of diagnostic and support procedures, days as in patients,
      number of day cases or outpatient attending) and an average NHS cost was applied
      to this resource use. All costs were summated over the period of palliation from
      the date of the first intervention with palliative intent until death. Although
      the patients in this study were not randomized, the two groups were matched to
      ensure comparability in clinical manifestation (uncomplicated biopsy proven
      oesophageal carcinoma) and the average age of patients from each group. A
      difference was identified between the length of survival in both patient groups
      and the analysis was corrected for this by estimating a cost per day of
      palliative support. Patients palliated with metal stents underwent fewer
      procedures and spent fewer days in hospital during the time period from
      presentation until death even when corrected for differences in survival. Patient
      outcome (effectiveness of palliation) was measured by recording mean dysphagia
      scores which were recorded before and after palliation. Metal stents were found
      to lead to a significantly higher improvement in dysphagia in comparison to
      conventional therapy. In addition, the mortality related to metal oesophageal
      stents was lower than Atkinson tube insertion. The average cost of palliation was
      much lower in the metal stent group (mean = pound sterling 2817) compared with
      the cost in those palliated conventionally (mean = pound sterling 4566). However,
      once this was corrected for survival the difference in the cost of palliation on
      a per diem basis was reduced (metal stents = pound sterling 60 per day,
      conventional group = pound sterling 72 per day). The results of our study
      indicate that the initial high cost of metal stents is more than outweighed by
      resource savings elsewhere in the hospital by virtue of reduced need for re
      intervention and shorter length of hospital in patient stay. Such cost savings
      taken in combination with the improved clinical effectiveness and low mortality
      related to metal stents provide significant support for introducing their use
      into clinical practice.

PMID- 10210339
TI  - Bowel preparation for the double-contrast barium enema: how to maintain coating
      with cleansing?
AB  - AIM: Poor mucosal coating, due to excess of fluid in the colon lumen, is a
      problem when the oral lavage method (4 litres of an iso-osmotic saline solution
      containing polyethylene glycol) is used as a preparation for double-contrast
      barium enema. Our aim was to assess the value of prior administration of
      sennosides to obtain a clean colon with a reduced volume of polyethylene glycol
      (PEG)-saline solution, but maintaining good mucosal coating. MATERIALS AND
      METHODS: After a 2-day low-residue diet, three different oral preparations were
      compared: (i) 4 litres of a PEG-saline solution (SELG) and 15 mg of bisacodyl
      (116 patients, SELG-4 group); (ii) 156 mg of sennosides, 15 g of magnesium
      sulphate, and 2 litres of water (116 patients, SennMg group); (iii) 156mg of
      sennosides and 2 litres of SELG (116 patients, SennSELG group). Compliance,
      complaints, cleansing, mucosal coating, and fluid retention were evaluated.
      RESULTS: Compliance was > 94% in every group. A higher percentage of mild nausea
      was observed in SELG-4 group, of mild abdominal cramping in SennMg group, of
      substantial abdominal cramping in SennSELG group (P < 0.02). Cleansing was better
      in SennSELG than in both the SELG-4 (P = 0.0003) and SennMg (P = 0.0353) group.
      Mucosal coating was better in SennMg than both SELG-4 (P = 0.0034) and SennSELG
      (P < 0.0001) group. There was more residual fluid in the SennSELG group than both
      in SELG-4 (P = 0.0029) and SennMg (P = 0.0059) group. CONCLUSION: For colon
      cleansing, the combination of sennosides and PEG-saline solution was better than
      either the 4 litre PEG protocol or the combination of sennosides and magnesium
      sulphate. For mucosal coating, the protocol combining sennosides and magnesium
      sulphate was more effective than either protocols using the PEG-saline solution.
      This may be due to the interaction of residual magnesium ions in the colon lumen
      with the barium suspension.

PMID- 10210340
TI  - Hepatic arterial infusion chemotherapy using percutaneous catheter placement with
      an implantable port: assessment of factors affecting patency of the hepatic
      artery.
AB  - OBJECTIVE: To assess the factors affecting patency of the hepatic artery during
      hepatic arterial infusion chemotherapy (HAIC) with an implantable port system
      inserted percutaneously. PATIENTS AND METHODS: Ninety patients with malignant
      hepatic tumours were given HAIC using percutaneous catheter placement. An end
      hole catheter was inserted into the hepatic artery (conventional method) in 41
      patients. An end-closed and side-hole catheter was used in 49 patients, in which
      the catheter tip was fixed in the gastroduodenal artery and the side hole was
      placed in the common hepatic artery (fixed catheter-tip method). The patency of
      the hepatic artery was evaluated with computed tomography (CT) arteriography
      using the implantable port system and angiography. Then, the factors affecting
      hepatic arterial patency were analysed. RESULTS: Hepatic arterial occlusion was
      observed in 15 patients (17%). The overall patency of the hepatic artery was
      86.9%, 78.4% and 51.5% at 6 months, 1 year and 2 years, respectively. The patency
      rate of the hepatic artery was significantly higher in patients with catheter
      placement using fixed catheter-tip method than those using conventional method (P
      = 0.01), and in patients without transcatheter arterial chemoembolization (TACE)
      prior to catheter placement than those with prior TACE (P = 0.01). When the
      variables affecting patency of the hepatic artery were studied together by
      multivariate analyses, the important factors were the method of catheter
      placement and the presence or absence of prior TACE. CONCLUSION: We consider that
      it is important for long-term patency of the hepatic artery during HAIC to use
      fixed catheter-tip method for percutaneous catheter placement instead of
      conventional method, and to select patients without prior TACE.

PMID- 10210342
TI  - Hyperechoic renal papillae as a physiological finding in neonates.
AB  - AIM: The increased echogenicity of medullary pyramids in neonates and children is
      poorly understood. Hence we conducted a prospective ultrasound study of the
      kidneys of neonates and fetuses. Hence we conducted a prospective ultrasound
      study of the kidneys of neonates and fetuses. PATIENTS AND METHODS: Ultrasound
      images of kidneys in neonates and fetuses in late pregnancy were analysed.
      RESULTS: Thirteen percent of the studied neonates showed hyperechogenicity in the
      renal papillae that disappeared spontaneously within 1 week, although no
      hyperechoic papillae were seen in any of the fetuses. Urine volume of the
      neonates with hyperechogenicity was significantly less than that of those without
      it. CONCLUSION: The fact that no hyperechoic findings appeared before the 34th
      week of gestation suggests that maturation of renal tubules and ability to
      concentrate urinary substances were contributing factors. Because only the tips
      of the pyramids were hyperechogenic, however, the term hyperechoic papillae would
      seem more appropriate than hyperechoic pyramids, the term generally used today.

PMID- 10210341
TI  - Bezoars in the stomach and small bowel--CT appearance.
AB  - AIM: The aim of this study was to present the computed tomography (CT) appearance
      of trichobezoars, phytobezoars and other unusual ingested material. MATERIALS AND
      METHODS: Seven patients diagnosed on CT with bezoars in the stomach or small
      intestine were reviewed with special attention on the characteristics of the
      intraluminal mass and the presence of proximal dilatation. RESULTS: There were
      six women and one man aged 14-81 years. CT was performed because of abdominal
      pain and a palpable abdominal mass. In none of the cases was the diagnosis
      suspected clinically. Four patients had a trichobezoar occupying the entire lumen
      of the stomach. It appeared as a concentric inhomogeneous mass with entrapped
      air, surrounded by contrast material. In the other three patients the bezoar was
      confined to the small intestine and was composed respectively of vegetable
      fibres, ingested toilet paper and an olive stone. The first two had a mottled
      appearance whereas the last one was small, spherical and well defined. Variable
      proximal dilatation of the small bowel was present in all three. CONCLUSION: With
      the increased use of CT in the evaluation of patients with non-specific abdominal
      pain, it is important to recognize the CT appearance of bezoars, as this
      diagnosis is often not suspected clinically.

PMID- 10210343
TI  - Metastases to pelvic lymph nodes from carcinoma in the pelvic cavity: diagnosis
      using thin-section CT.
AB  - OBJECTIVE: To assess the accuracy of thin-section computed tomography (CT) in the
      diagnosis of pelvic lymph nodes affected by metastatic cancer. METHODS:
      Incremental CT was performed by obtaining 3 mm sections with 3 mm intervals in 34
      patients who had carcinoma in the pelvis, pre-operatively and prospectively. CT
      diagnoses were made before surgery using the cine mode with a manual trackball.
      Lymph nodes with a maximum short axis diameter of greater than 5 mm were
      considered enlarged. RESULTS: The accuracy, sensitivity, specificity, positive
      and negative predictive values of CT diagnoses were 79.7%, 54.5%, 84.9%, 42.9%
      and 90.0% on a hemipelvis basis; and 79.4%, 85.7%, 77.8%, 50.0% and 95.5% on a
      patient basis, respectively. There was only one false-negative case on a patient
      basis analysis. CONCLUSION: Because of a fairly high negative predictive value,
      negative thin-section CT can be considered an alternative to surgical
      lymphadenectomy. This is clinically important as unnecessary staging operations
      and extended surgery are avoided.

PMID- 10210344
TI  - The significance of new densities and microcalcification in the second round of
      breast screening.
AB  - AIM: To assess the nature of new densities and microcalcifications in the second
      round of breast screening. MATERIALS AND METHODS: A total of 34 634 women were
      screened at our unit in the second round of the United Kingdom National Health
      Service Breast Screening Programme. Of those attending for the second time, 302
      were recalled for further work-up of 311 new lesions. The lesions were divided
      into masses, microcalcifications, asymmetric densities and architectural
      distortions. Masses were classified according to margin and density, and
      microcalcifications according to morphology and distribution. RESULTS: Among
      women attending for the second time, the cancer detection rate was 0.45% (89
      cancers). One hundred and eighty-eight new masses were identified: 53 well
      defined (two malignant), 67 partially defined (six malignant), 54 ill-defined (18
      malignant), and 14 spiculate (14 malignant). Well-defined masses were usually
      cysts, especially in women on hormone replacement therapy. Of 97 new
      microcalcifications, 71 were pleomorphic (28 malignant), 12 linear (one
      malignant), and 14 punctate (none malignant). Twenty-five new asymmetric
      densities were identified (five malignant). One of two architectural distortions
      was malignant. Malignancy was found in 21% of new masses, 30% of new
      microcalcification and 20% of asymmetric densities. CONCLUSION: Carcinoma was
      found in 24% of all new mammographic abnormalities appearing in a 3-year
      screening period. Spiculate and ill-defined masses, clustered pleomorphic
      microcalcification, and new asymmetric densities should be regarded with
      particular suspicion. The use of fine needle aspiration cytology in combination
      with imaging assessment may help to reduce the number of benign excisional
      biopsies for new mammographic lesions.

PMID- 10210345
TI  - Contribution of PET in the detection of liver metastases from pancreatic tumours.
AB  - AIM: Although uptake of 2-deoxy-2-[fluorine-18]fluoro-D-glucose (FDG) in the
      liver is basically high, metastatic liver tumours are known to be positive on
      positron emission tomography (PET). The purpose of this study is to evaluate the
      diagnostic accuracy of FDG-PET in detecting hepatic metastases from pancreatic
      cancer. METHODS: Thirty-four patients with histologically proven malignant
      tumours of the pancreas underwent FDG-PET, computed tomography (CT) and
      transabdominal ultrasound (US). The findings of PET, CT and US were compared with
      the histopathologic findings at surgery or with clinical follow-up and the
      diagnostic accuracy of PET was evaluated. RESULTS: PET showed 28 regions of high
      FDG uptake (SUV = 3.3-9.1) in 13 patients. Twenty-six foci were metastatic
      lesions confirmed by surgery (n = 11), clinical follow-up (n = 10) or autopsy (n
      = 5). FDG-PET accurately differentiated seven metastatic lesions from cysts when
      the diagnosis by US or CT was unreliable because of the small size of the lesion.
      In two patients who had areas of high uptake in the liver, no metastases were
      detected by surgery. FDG-PET showed no areas of increased uptake in 21 patients.
      Surgery revealed no metastatic lesions in the liver in 20 of 21 patients, but a
      liver metastasis was found at surgery in one patient. The diagnostic accuracy of
      FDG-PET was 90%, which was comparable with that of US or CT. CONCLUSION: Our data
      suggest that PET is reliable in detecting liver, metastases from pancreatic
      cancer.

PMID- 10210346
TI  - Preservation of hypervascularity in hepatocellular carcinoma after effective
      proton-beam radiotherapy--CT observation.
AB  - AIM: The aim of this study was to describe persistence of hypervascularity in
      proton treated hepatocellular carcinoma at serial follow-up computed tomography
      (CT). METHODS: Four patients with unresectable solitary hypervascular
      hepatocellular carcinoma underwent 55-82 Gy proton-beam irradiation for a period
      of 15-47 days. Follow-up CT including plain, enhanced and dynamic imaging was
      performed for a period of 9-36 months. RESULTS: Good preservation of arterial
      blood supply while gradual decrease in tumour size was clearly depicted by
      dynamic CT. CONCLUSION: We believe that preservation of hypervascularity as
      judged by enhancement at CT and magnetic resonance imaging, does not necessarily
      mean that radiotherapy in hypervascular malignant tumours has been unsuccessful.

PMID- 10210347
TI  - Gastric tuberculosis: unusual presentations in two patients.
AB  - We report two cases of gastric tuberculosis (TB) in Nigerians. The first case
      concerns an elderly man initially thought to have abdominal malignancy but was
      subsequently found to have extensive and complicated gastric TB coexisting with
      chronic peptic ulcer disease. The second case involved the extremely rare
      condition of gastro-bronchial fistula in a young woman. In contrast to previously
      reported cases, it was of tuberculous origin and pulmonary symptoms were minimal.
      Both cases were radiologically evident.

PMID- 10210348
TI  - North American blastomycosis in South Africa simulating tuberculosis.

PMID- 10210349
TI  - Unusual MR appearance in a branchial cyst.

PMID- 10210350
TI  - Diagnosis and management of uterine arterio-venous malformations.

PMID- 10210351
TI  - MRI and CT in a case of pituitary abscess.

PMID- 10210352
TI  - 24-hour radiology coverage.

PMID- 10210353
TI  - Azygos reflux: a CT sign of cardiac tamponade.

PMID- 10210354
TI  - Detection of simulated pulmonary nodules by spiral CT.

PMID- 10210355
TI  - Lovastatin preserves renal function in experimental diabetes.
AB  - Although hyperlipidemia has been associated with the progression of
      glomerulosclerosis, little attention has been directed toward the use of lipid
      lowering agents in altering diabetic nephropathy. We tested the hypothesis that
      lovastatin and the combination of lovastatin and enalapril would preserve renal
      function in streptozotocin-induced diabetic Wistar rats. Five groups of animals
      were studied: group 1, nondiabetic (n = 10); group 2, diabetic, insulin only (n =
      12); group 3, lovastatin, (15 mg/kg/day, n = 13); group 4, enalapril, (50 mg/L
      drinking water, n = 10) and group 5, lovastatin plus enalapril, (n = 14). After 8
      weeks of treatment, glomerular filtration rate (GFR, insulin clearance) was
      measured in anesthetized animals. The diabetic group was characterized by a GFR
      of 0.18 +/- 0.03 ml/min/g of kidney weight (gKW), a blood glucose level of 441 +/
      36 mg/dL, plasma cholesterol and triglyceride levels of 64 +/- 6.0 and 103 +/-
      26.0 mg/dL. Lovastatin preserved GFR, 0.52 +/- 0.06 ml/min/gKW compared with the
      diabetic control subjects (P < 0.05). Enalapril also maintained GFR (0.42 +/-
      0.06 ml/min/gKW, P < 0.05). In the lovastatin plus enalapril group, GFR (0.62 +/-
      0.05 ml/min/gKW) was greater than in the enalapril group (P < 0.05), but was not
      different from the lovastatin group. Plasma lipid levels were not altered in any
      of the groups. Assessment of the kidneys by histology after treatment showed that
      the mesangial matrix injury score was better in the lovastatin, enalapril, and
      lovastatin plus enalapril groups compared with the diabetic group (P < 0.05).
      Lovastatin, enalapril, and lovastatin plus enalapril abrogated the decline in GFR
      and glomerular injury in diabetic rats. Lovastatin's direct renal protective
      effect seems to be independent of its lipid-lowering properties.

PMID- 10210356
TI  - Comparison of bronchoalveolar lavage cell findings in complete-resolution
      pneumonia and delayed-resolution pneumonia.
AB  - BACKGROUND: In some patients with bacterial pneumonia, the resolution of chest
      radiograph shadows are delayed. There have been many clinical and pathological
      studies on delayed-resolution pneumonia (DR). However, there are no reports
      concerning inflammatory cell findings of bronchoalveolar lavage (BAL) fluid in
      patients with DR. We compared the BAL fluid cell findings in patients with DR
      with those in patients with complete-resolution pneumonia (CR). METHODS: The
      subjects included six patients whose chest radiograph shadows were completely
      resolved within 2 weeks after an appropriate antibiotic administration (CR), and
      nine patients whose chest radiograph shadows were unresolved more than 2 weeks
      after the treatment (DR). BAL was done 2-3 weeks after the antibiotic treatment
      in both groups. We compared differential counts and lymphocyte subsets in BAL
      fluid among patients with CR, patients with DR, and asymptomatic subjects.
      RESULTS: There were no significant differences in BAL fluid cell findings between
      CR groups and asymptomatic groups. On the other hand, the percentages of
      lymphocytes, neutrophils and eosinophils in DR group were significantly increased
      compared with those in CR and normal groups. There was no significant difference
      in the CD4+/CD8+ ratio of BAL lymphocytes among the three groups. CONCLUSIONS: It
      is suggested that infiltration of inflammatory cells in the lung exists in DR,
      despite the disappearance of inflammatory reaction in the peripheral blood.

PMID- 10210357
TI  - Gastric myoelectrical activity, gastric emptying, and correlations with symptoms
      and fasting blood glucose levels in diabetic patients.
AB  - BACKGROUND: The aims of this study were to determine the electrogastrogram (EGG)
      changes and gastric emptying rates in diabetic patients and to investigate the
      correlation between upper gastrointestinal symptoms, fasting blood glucose, and
      gastric myoelectrical abnormalities. METHODS: Fourteen patients with long
      standing type 1 diabetes mellitus and dyspepsia symptoms participated in the
      study. EGG recordings were obtained 30 minutes before and during a 2-hour
      radionuclide gastric emptying test for a solid meal. Fasting blood glucose was
      determined immediately before the gastric emptying study. Symptoms of nausea,
      vomiting, early satiety, abdominal bloating, and pain were rated from 0 to 3.
      RESULTS: Nine patients (64%) had delayed gastric emptying with 84.6 +/- 4.5%
      retention at 2 hours. Seven patients (50%) had abnormal EGG findings. The
      postprandial power change in the EGG of the patients with delayed gastric
      emptying (-0.48 +/- 0.16 dB) was decreased compared with patients with normal
      gastric emptying (4.7 +/- 2.6 dB) (P = 0.079). In patients with abnormal EGGs,
      the mean symptom score was significantly higher than patients with normal EGGs
      (2.42 +/- 0.13 versus 2.0 +/- 0.16; P < 0.05). Compared with normal gastric
      emptying patients, patients with delayed gastric emptying had higher but not
      significantly different symptom scores (2.31 +/- 0.11 versus 2.08 +/- 0.30; P =
      0.225). There was no significant difference in fasting glucose levels in delayed
      (252 +/- 61.2 mg/dl) versus normal (378 +/- 82 mg/dl) gastric emptying or
      abnormal (288 +/- 86.4 mg/dl) EGGs versus patients with normal (304 +/- 57.6
      mg/dl) EGGs. CONCLUSIONS: Overall, 78% (11 of 14) of patients with diabetes had
      either gastric motility or myoelectrical abnormalities. Patients with abnormal
      EGGs had more severe symptom scores. In diabetic patients with symptoms of
      gastropathy, an EGG may provide an important screening test for diagnosing
      abnormal gastric motility.

PMID- 10210358
TI  - Absence of age-related increase in systolic blood pressure in ambulatory patients
      with HIV infection.
AB  - BACKGROUND: Systolic blood pressure is well known to increase significantly with
      age and is strongly correlated with stroke and coronary artery disease. We and
      other investigators have reported a low prevalence of hypertension in subgroups
      of patients with HIV infection. In the present study, we examined an ambulatory
      population of patients with HIV infection to determine whether in the outpatient
      setting they may lack an age-related increase in systolic blood pressure.
      METHODS: In an ambulatory outpatient practice, medical records of 178 consecutive
      patients with HIV infection and those of 200 control subjects were examined.
      Systolic and diastolic blood pressure and other clinical and laboratory variables
      were recorded. Scatter plots were generated to compare age with systolic blood
      pressure. Spearman rank correlation analysis was carried out to determine the
      relationship between systolic blood pressure and age and other variables.
      RESULTS: Patients ranged in age from 13 to 69 years. There was only a very slight
      increase (which did not achieve statistical significance) in systolic blood
      pressure with aging in the patients with HIV infection, in contrast to the
      control population, in which an age-related increase in systolic blood pressure
      was seen that was comparable to published Framingham data. Mean systolic blood
      pressure for the group as a whole was 118.2 +/- 1.1 mm Hg. Mean serum albumin was
      4.2 +/- 0.04 g/dL and was only slightly diminished in older patients. Mean serum
      cholesterol was 176.8 +/- 3.4 mg/dL and this bore no relationship to aging. More
      advanced stages of HIV infection also did not correlate with the lack of age
      associated systolic hypertension. CONCLUSION: The present population of
      ambulatory patients infected with HIV seem to lack an age-related increase in
      systolic blood pressure; this may be caused by such variables as autonomic
      dysfunction or factors that may attenuate the development of atherosclerosis.

PMID- 10210359
TI  - Polyarteritis nodosa: a report from Israel.
AB  - BACKGROUND: The clinical manifestations and outcome of all adult patients with
      polyarteritis nodosa (PAN), allocated during a 15-year period in the largest
      medical center in Israel, were examined. METHODS: A retrospective analysis of
      patients with PAN who fulfilled the American College of Rheumatology (ACR) 1990
      Classification Criteria and were either biopsy- or angiography-proven. RESULTS:
      Nine patients were included in the report. The clinical and laboratory
      manifestations were similar to those in previous studies. All patients were
      treated with combinations of cyclophosphamide and corticosteroids. There were two
      (22%) deaths, 2 and 5 months after initiation of treatment in patients who
      probably had microscopic polyangiitis (MPA) rather than classical PAN.
      Considering the patients with a complete follow-up, 71% had a complete and long
      term remission. Moreover, by exclusion of the two patients with probable MPA who
      died, all of the five patients with classical PAN were alive and well as of this
      writing. Two patients (22%) had a long history, since childhood, of familial
      Mediterranean fever (FMF). CONCLUSIONS: The clinical presentation and course of
      PAN in Israeli patients is comparable with reports elsewhere. However, a
      distinction should be made between PAN and MPA. The present report emphasizes the
      good long-term prognosis of patients with typical PAN who are treated adequately.
      In addition, a possible association of PAN with FMF in Israeli patients is
      suggested.

PMID- 10210360
TI  - Multidisciplinary evidence-based medicine journal clubs: curriculum design and
      participants' reactions.
AB  - BACKGROUND: Evidence-based medicine (EBM) is becoming an accepted educational
      paradigm in medical education at a variety of levels. It focuses on identifying
      the best evidence for medical decision making and applying that evidence to
      patient care. METHODS: Three EBM journal clubs were developed at the West
      Virginia University School of Medicine. One was for senior medical students,
      another for residents, and the third for primary care faculty members. In each,
      the sessions stressed answering clinical questions arising from actual patient
      care issues. The curricular structure and development of the journal clubs are
      described. Participants anonymously evaluated aspects of the journal clubs
      regarding their educational value with Likert scale questions. RESULTS: Faculty
      members and residents generally gave high evaluations to all aspects of the EBM
      journal clubs. Student evaluations were more mixed. For each of the evaluation
      questions, the student means were lower than those of faculty and residents.
      However the differences reached statistical significance only in the responses to
      the usefulness of the sessions in understanding the medical literature (P <
      0.01). Residents and faculty rated the EBM sessions more favorably than grand
      rounds or the resident lecture series. CONCLUSIONS: The establishment of evidence
      based medicine journal clubs is feasible, and learners seem to value the
      sessions. More developed learners may gain more from the experience than those
      earlier in their medical education.

PMID- 10210361
TI  - New treatment strategies in patients with impaired left ventricular systolic
      function. Part I: Background and treatment of mild cardiac dysfunction.

PMID- 10210362
TI  - Update on renal osteodystrophy: pathogenesis and clinical management.

PMID- 10210363
TI  - Lactic acidosis caused by thiamine deficiency in a pregnant alcoholic patient.
AB  - BACKGROUND: Metabolic acidosis from accumulation of lactic acid is a relatively
      common condition, whereas its causation by thiamine deficiency is not. METHODS:
      We studied a pregnant alcoholic patient who presented with hyperemesis and a high
      anion gap acidosis. RESULTS: Lactic acidosis and thiamine deficiency were
      confirmed. The patient's symptoms and acidosis resolved with thiamine
      administration. CONCLUSIONS: Lactic acidosis caused by thiamine deficiency must
      be suspected when pregnant patients at risk for thiamine deficiency present with
      a high anion gap acidosis. A large dose of thiamine must be administered
      immediately.

PMID- 10210364
TI  - Bacillus popilliae endocarditis with prolonged complete heart block.
AB  - Bacillus popilliae, a fastidious, aerobic, gram-positive, spore-forming bacillus,
      has never been reported as a pathogen in human infectious diseases. We report the
      first case of a human infected by the pathogen B. popilliae, which presented as
      endocarditis involving the bicuspid aortic valve and complicated with prolonged
      (> 30 days; to our knowledge, the longest in the literature) complete heart
      block. Although surgery may be warranted by previous reports, the patient was
      successfully managed by medical treatment instead, because of the absence of
      evidence from various approaches that support the existence of perivalvular
      extension of infection.

PMID- 10210365
TI  - Angiotropic large cell lymphoma presenting as fever of unknown origin.
AB  - BACKGROUND: Fever has never before been described as the chief complaint and
      major finding in angiotropic large cell lymphoma (ALCL). ALCL is a rare and
      usually fatal intravascular tumor characterized by a widespread proliferation of
      malignant mononuclear cells within vessels of small caliber, causing their
      blockage. The majority present as high-grade, B-cell lymphomas with a
      predilection for the central nervous system and the skin. CASE REPORT: We report
      a 61-year-old woman who presented with a fever of unknown origin (FUO) that
      lasted 9 weeks from onset to death. To our knowledge, this is the first case of
      ALCL to present solely as a FUO, and the second case of ALCL to be diagnosed by
      muscle biopsy. CONCLUSION: We suggest that this rare malignancy (ALCL) be
      considered in the differential diagnosis of FUO.

PMID- 10210366
TI  - Organic arsenic intoxication from bird's nest soup.
AB  - OBJECTIVE: To present a case of organic arsenic intoxication after consumption of
      bird's nest soup in a Vietnamese patient. METHOD: We have described the clinical
      picture of a patient with organic arsenic intoxication, and high levels of urine
      arsenic after consumption of bird's nest soup. RESULT: Withdrawal of bird's nest
      soup coincided with a decrease in urinary arsenic levels and the disappearance of
      peripheral neuropathy. CONCLUSION: This case illustrates the environmental
      contamination of bird's nest soup with organic arsenic. A prompt removal of the
      source from the diet resulted in clinical improvement.

PMID- 10210367
TI  - Crystalluria in patients with calcium stone disease.

PMID- 10210368
TI  - Pelvic fracture urethral injuries: the unresolved controversy.
AB  - PURPOSE: The unresolved controversies about pelvic fracture urethral injuries and
      whether any conclusions can be reached to develop a treatment plan for this
      lesion are determined. MATERIALS AND METHODS: All data on pelvic fracture
      urethral injuries in the English literature for the last 50 years were critically
      analyzed. Studies were eligible only if data were complete and conclusive.
      RESULTS: The risk of urethral injury is influenced by the number of broken pubic
      rami as well as involvement of the sacroiliac joint. Depending on the magnitude
      of trauma, the membranous urethra is first stretched and then partially or
      completely ruptured at the bulbomembranous junction. Injuries to the prostatic
      urethra and bladder neck occur only in children. Injury to the female urethra
      usually is a partial tear of the anterior wall and rarely complete disruption of
      the proximal or distal urethra. Diagnosis depends on urethrography in men and on
      a high index of suspicion and urethroscopy in women. Of the 3 conventional
      treatment methods primary suturing of the disrupted urethral ends has the
      greatest complication rates of incontinence and impotence (21 and 56%,
      respectively). Primary realignment has double the incidence of impotence and half
      that of stricture compared to suprapubic cystostomy and delayed repair (36 versus
      19 and 53 versus 97%, respectively, p <0.0001). CONCLUSIONS: In men surgical and
      endoscopic procedures do not compete but rather complement each other for
      treatment of different injuries under different circumstances, including
      indwelling catheter for urethral stretch injury, endoscopic stenting or
      suprapubic cystostomy for partial rupture, endoscopic realignment or suprapubic
      cystostomy for complete rupture with a minimal distraction defect and surgical
      realignment if the distraction defect is wide. Associated injury to the bladder,
      bladder neck or rectum dictates immediate exploration for repair but does not
      necessarily indicate exploration of the urethral injury site. In women treatment
      modalities are dictated by the level of urethral injury, including immediate
      retropubic realignment or suturing for proximal and transvaginal urethral
      advancement for distal injury.

PMID- 10210369
TI  - Molecular determination of surgical margins using fossa biopsies at radical
      prostatectomy.
AB  - PURPOSE: Status of the surgical margins after radical prostatectomy is a key
      factor for predicting postoperative outcome. Current methods used to determine
      margin status are tedious, costly and vary among institutions. Sensitive and
      inexpensive detection of prostate cells in the circulation of patients with
      prostate cancer has been achieved using reverse transcriptase (RT) polymerase
      chain reaction (PCR) for prostate specific antigen and prostate specific membrane
      antigen. Therefore, we designed and tested a novel and objective molecular assay
      for assessing surgical margins at radical prostatectomy based on the detection of
      prostate specific markers using RT-PCR. We also compared this assay to standard
      pathological examination. MATERIALS AND METHODS: A total of 30 consecutive
      patients with local prostate cancer underwent radical prostatectomy. At the
      completion of gland excision 5 biopsies of the prostatic fossa were obtained for
      histopathological and molecular analysis. We performed RT-PCR analysis for
      prostate specific antigen and prostate specific membrane antigen messenger
      ribonucleic acid in these biopsy specimens, and compared the results with
      pathological stage. Men free of prostate cancer who underwent radical
      cystoprostatectomy for bladder cancer or abdominoperineal resection for rectal
      cancer served as controls. RESULTS: There were positive molecular margins in all
      patients with positive margins and/or extracapsular extension. No controls had a
      positive molecular assay. In 4 of 16 patients (25%) histopathological evaluation
      revealed organ confined disease but biopsies were positive by the molecular
      assay, including those in 2 (50%) who had been treated with neoadjuvant hormonal
      therapy before surgery because of a higher estimated risk of extracapsular
      disease. Results in 4 cases were uninformative. CONCLUSIONS: Our results with an
      objective molecular assay aimed at assessing surgical margins after radical
      prostatectomy reveal an excellent correlation with conventional pathological
      analysis. In addition, molecular assessment of the prostatic fossa identifies
      patients in whom extracapsular disease may have been unidentified by conventional
      pathological examination. In addition, this assay yields clues to why neoadjuvant
      hormonal treatment before radical prostatectomy does not seem to decrease the
      biochemical failure rate in these patients. Larger studies with longer followup
      are required to determine the prognostic significance of these positive molecular
      margins.

PMID- 10210370
TI  - Comparison of comprehensive and limited metabolic evaluations in the treatment of
      patients with recurrent calcium urolithiasis.
AB  - PURPOSE: We compared diagnostic information from limited and comprehensive
      metabolic evaluations of recurrent calcium stone formers. MATERIALS AND METHODS:
      A total of 74 men and 45 women with recurrent calcium stones underwent
      comprehensive metabolic evaluation. The number of specific and total metabolic
      abnormalities diagnosed on 1 or 2 random 24-hour urinalyses were compared to
      those obtained on a comprehensive metabolic evaluation. We also examined the
      ability of the comprehensive evaluation to detect dietary calcium sensitive
      oxaluria. RESULTS: The comprehensive metabolic evaluation yielded a specific
      metabolic diagnosis in 90% of the patients compared to 68% for 1 and 75% for 2
      urinalyses. Average total number of specific metabolic abnormalities for each
      patient was approximately 50% higher on a comprehensive metabolic evaluation
      compared to 1 urinalysis (1.59 +/- 0.08 versus 0.94 +/- 0.07, p <0.05).
      Hypercalciuria, hyperoxaluria and hypocitruria were diagnosed significantly more
      often by the comprehensive than by the limited evaluation. Type II absorptive
      hypercalciuria was the most common pattern of hypercalciuria, and dietary calcium
      sensitive oxaluria was present in 22% of the patients. CONCLUSIONS: Comprehensive
      metabolic evaluation yields significantly more useful diagnostic information and
      allows implementation of a more specific therapeutic plan than limited metabolic
      evaluation for the recurrent calcium stone former.

PMID- 10210371
TI  - The efficacy of potassium citrate based medical prophylaxis for preventing upper
      urinary tract calculi: a midterm followup study.
AB  - PURPOSE: We examined the efficacy of potassium citrate based medical prophylaxis
      for preventing upper urinary calculous recurrence, and compared it with the stone
      recurrence rate in patients who only received intermittent or no medical
      prophylaxis. MATERIALS AND METHODS: We retrospectively reviewed the records of
      493 patients with upper urinary calculi, of whom 237 men and 76 women with a mean
      age of 56.1 and 51.4 years, respectively, were enrolled in the study. Of the 313
      participants 64 (group 1, 20.4%) received regular medical prophylaxis for 24 to
      42 months (mean 27.8), 80 (group 2, 25.6%) received intermittent medical
      prophylaxis for 1.5 to 19 months (mean 7.9) and 169 (group 3, 54%) did not
      receive any medical prophylaxis. RESULTS: At midterm followup of 24 to 60 months
      107 patients (34.2%) had stone recurrence. In group 1 the stone recurrence rate
      was 7.8%, which was significantly less (p <0.001) than in groups 2 (30%) and 3
      (46.2%). Similarly new calculous events in patients with a history of multiple
      stone recurrence were less frequent in group 1 than in groups 2 and 3 (9.7, 47.4
      and 52.2%, respectively, p <0.001). Multiple stone recurrence history,
      hypercalciuria, hyperuricosuria and calcium oxalate dihydrate calculi were
      independent risk factors for stone recurrence. CONCLUSIONS: Regular medical
      prophylaxis may effectively prevent stone recurrence regardless of previous
      treatment modalities, stone composition, metabolic abnormalities and stone-free
      status. Cost effectiveness, patient compliance and gastrointestinal upset may
      limit patient acceptability and clinical use of medical prophylaxis. However,
      patients with a history of multiple stone recurrence, calcium oxalate dihydrate
      stones, hypercalciuria and hyperuricosuria benefit from regular medical
      prophylaxis.

PMID- 10210372
TI  - Urolithiasis in renal and combined pancreas/renal transplant recipients.
AB  - PURPOSE: Urological complications in renal transplant recipients will become more
      common with increasing numbers of transplantations as well as increased graft
      survival secondary to improvements in immunosuppression. Urinary stone disease
      may be one of those complications. We determine the current incidence of urinary
      stone disease in renal transplant patients based on contemporary
      immunosuppressive regimens. MATERIALS AND METHODS: We reviewed the records of
      1,730 renal and 83 pancreas/renal transplantations performed during the
      cyclosporine era and identified 8 recipients (0.4%) with urinary stone disease,
      including 3 with renal pelvic stones, 1 with multiple ureteral stones and 4 with
      bladder calculi. RESULTS: Treatment ranged from conservative observation to open
      pyelolithotomy, and included percutaneous nephrolithotomy and extracorporeal
      shock wave lithotripsy. The ureteral stones were removed with antegrade and
      retrograde ureteroscopy. The 4 bladder stones were treated with cystolithalopaxy.
      No case had significant permanent graft damage. Mean followup was 68.6 months.
      Mean serum creatinine was 1.5 mg./dl. (normal 0.5 to 1.3) at baseline and 2.38
      after followup. CONCLUSIONS: While the incidence of upper tract urinary stone
      disease in renal (0.23%) and pancreas/renal (1.2%) transplant recipients is not
      statistically significant (p <0.45), the latter have significantly higher rates
      of bladder stones (4.8 versus 0%, p <0.001). The diagnosis of urinary stone
      disease in transplant recipients can be challenging because of the lack of
      symptoms but the treatment approach is the same as in the normal population.

PMID- 10210373
TI  - The role of C-reactive protein in graft dysfunction after renal transplantation.
AB  - PURPOSE: We investigated whether serial daily measurements of serum C-reactive
      protein could help differentiate episodes of transplant dysfunction due to
      rejection, infection, cyclosporin A nephrotoxicity or acute tubular necrosis in
      renal allograft recipients. MATERIALS AND METHODS: Morning serum was obtained
      daily from 134 patients during the first 30 days after renal transplantation. All
      episodes of graft dysfunction were recorded and compared to transplant biopsies.
      C-reactive protein concentrations were correlated with postoperative graft
      function and the various causes of graft dysfunction. RESULTS: All patients
      demonstrated an increase in C-reactive protein in response to surgery and a
      maximum level was reached on day 2 after transplantation. Mean C-reactive protein
      concentration was significantly increased for delayed (61.50 microg./ml.)
      compared to primary (mean 38.01) graft function (p = 0.001, Mann-Whitney U test).
      There were significant increases in C-reactive protein for bacterial infections
      other than asymptomatic bacteriuria (33.98 microg./ml), interstitial graft
      rejection (16.43) and acute tubular necrosis (30.50) compared to uneventful
      courses. C-reactive protein was unchanged for viral infections or cyclosporin A
      toxicity. CONCLUSIONS: Serial C-reactive protein measurements help to identify
      renal transplant dysfunction of different origins. However, rejection, infection
      and acute tubular necrosis show similar patterns of C-reactive protein increase.
      Thus, C-reactive protein is unable to discriminate the causes of renal graft
      dysfunction. Biopsy remains the gold standard for the differential diagnosis of
      renal allograft dysfunction.

PMID- 10210374
TI  - The morbidity of prolonged wound drainage after kidney transplantation.
AB  - PURPOSE: The consequences of prolonged wound drainage, defined as extravasation
      of more than 50 ml. fluid daily for more than 1 week through a drain or wound
      after renal transplantation, have not been well described in the literature. We
      examine the association of prolonged wound drainage with other clinical events,
      and its impact on hospitalization, and patient and graft survival. MATERIALS AND
      METHODS: We prospectively documented prolonged wound drainage in 392 recipients
      of cadaver and live renal transplants from July 1993 to December 1997. Potential
      risk factors, associated outcomes within the first 6 months and effect on length
      of hospital stay due to prolonged wound drainage were determined. RESULTS:
      Prolonged wound drainage was significantly associated with pre-transplantation
      weight, weight gain by post-transplantation day 3, delayed graft function and
      continuous ambulatory peritoneal dialysis on univariate analysis but only with
      delayed graft function (odds ratio 2.8, 95% confidence intervals 1.4 to 5.6) on
      multivariate analysis. Post-transplantation lymphoceles (5.2, 9 to 14), wound
      infection (27, 5.7 to 130) and wound dehiscence (5.8, 1.7 to 20) were associated
      with prolonged wound drainage. Patients with prolonged wound drainage stayed 8.7
      additional days during the first hospitalization and overall 11.3 additional days
      during the first 6 months after transplantation independent of other co-morbid
      events, such as delayed graft function, rejection or cytomegalovirus disease.
      CONCLUSIONS: Prolonged wound drainage is an important post-renal transplantation
      event that impacts patient outcomes and hospital resource use. Efforts to prevent
      this complication should be considered.

PMID- 10210375
TI  - Imaging guided biopsy of renal masses: indications, accuracy and impact on
      clinical management.
AB  - PURPOSE: We evaluated the indications, accuracy and impact of image guided biopsy
      of focal renal masses. MATERIALS AND METHODS: We retrospectively reviewed 79
      image guided renal biopsies in 73 patients. Indications, imaging, and
      histological and clinical features were analyzed. We assumed that nephrectomy,
      partial nephrectomy or surgical biopsy of suspicious masses would be done when no
      percutaneous biopsy had been performed. A change in management was defined as
      surgical to nonsurgical. RESULTS: Clinical management was altered due to results
      in 32 of the 79 biopsies (41%) in cases managed nonoperatively, including
      positive and negative biopsies in those followed clinically and with imaging. Of
      79 biopsies 49 (62%) were diagnosed positive for malignancy, including 15 (31%)
      that were not and 34 (69%) that were renal cell carcinoma. The histological
      diagnosis was negative on 25 biopsies (32%) and positive or negative on 74 (94%).
      All 5 of the 79 false-negative biopsies (6%) were due to insufficient tissue and
      involved highly suspicious imaging findings that required further evaluation,
      such as repeat biopsy or surgery. Renal cell carcinoma was identified in 4 of the
      5 cases. In 12 of the 24 patients (50%) with a pre-biopsy history of nonrenal
      cancer biopsies were diagnostic of nonrenal cancer. No patient had major
      complications and in 4 small hematomas were treated with observation only.
      CONCLUSIONS: Image guided renal mass biopsy is safe, reliable and accurate, and
      it changes clinical management in many cases by avoiding nephrectomy or other
      surgical options. Radiologists should promote imaging guided biopsy as a
      potentially useful option for managing suspicious or indeterminate renal masses.

PMID- 10210376
TI  - Renal cancer in families with hereditary renal cancer: prospective analysis of a
      tumor size threshold for renal parenchymal sparing surgery.
AB  - PURPOSE: Patients with hereditary forms of renal cancer are at risk for new
      tumors and metastases. Renal parenchymal sparing surgery has been performed to
      preserve renal function and quality of life, and prevent metastases. We evaluated
      a 3 cm. threshold for performing renal parenchymal sparing surgery in patients
      with von Hippel-Lindau disease and hereditary papillary renal cancer. MATERIALS
      AND METHODS: Patients with von Hippel-Lindau disease or hereditary papillary
      renal cancer and renal cancer were identified by screening affected kindred and
      by kindred history. Patients with small tumors were followed with serial imaging
      studies until the largest renal tumor was 3 cm., when renal parenchymal sparing
      surgery was performed. Renal tumors greater than 3 cm. were resected without
      delay. Parenchymal sparing techniques were used when possible in each group.
      RESULTS: The 3 cm. surgical threshold was evaluated in 52 patients with von
      Hippel-Lindau disease (group 1) at a median followup of 60 months (range 6 to
      205). None of these patients had metastatic disease and none has required renal
      transplantation or dialysis. In 44 patients with von Hippel-Lindau disease (group
      2) renal tumors larger than 3 cm. developed. Median followup from the initial
      radiological diagnosis of renal cancer in this group was 66.5 months (range 0 to
      321). Patients in group 1 underwent parenchymal sparing surgery instead of
      nephrectomy more frequently than those in group 2 (46 of 48 operations or 96%
      versus 45 of 72 or 63%, Fisher's exact test p <0.0001). In contrast to patients
      in group 1, metastatic renal cancer developed in 11 of the 44 in group 2 (25%)
      (Fisher's exact test p <0.0001). A total of 23 patients with hereditary papillary
      renal cancer were also identified. Median followup in these cases was 44 months
      (range 0 to 237). Ten patients had tumors less than 3 cm. No patient with tumors
      less than 3 cm. and 2 of the 13 (15%) with larger tumors had metastases.
      CONCLUSIONS: Using a 3 cm. renal tumor diameter as an indication for renal
      surgery no patient with renal cancer and von Hippel-Lindau disease or hereditary
      papillary renal cancer had metastatic disease regardless of the number of tumors.
      Using a lesion size of 3 cm. as a threshold for performing renal parenchymal
      sparing surgery may help to prevent metastatic disease, unnecessary renal damage
      due to frequent surgery and renal dialysis or transplantation.

PMID- 10210377
TI  - Micturition after gastrocystoplasty and gastric bladder replacement.
AB  - PURPOSE: We determine the function of gastric tissue as a reservoir for urine and
      driving force for urination. MATERIALS AND METHODS: A total of 12 men 15 to 45
      years old underwent gastrocystoplasty (8) or gastric bladder replacement (4). In
      1 patient bladder neck reconstruction was performed with augmentation using the
      same gastric segment. Ten patients were followed for 1 to 2 years, and evaluated
      subjectively and objectively, including a urodynamic study 6 months
      postoperatively. RESULTS: No patient had dysuria or hematuria, despite urinary pH
      of 5 or less. Mean bladder capacity after augmentation increased from 130 (range
      60 to 150) to 420 ml. (range 400 to 470), and was 350 ml. (range 340 to 380)
      after gastric replacement. Uninhibited contractions occurred only when bladder
      filling reached 71 to 92% of ultimate capacity with a mean amplitude of 22 cm.
      water (range 5 to 38). Patients with a gastric neobladder demonstrated an
      interrupted biphasic flow pattern with a mean maximum flow rate of 12 ml. per
      second (range 11.5 to 12.8). Urine was evacuated mainly by contraction of the
      gastric bladder (74%) in stage 1 and by abdominal straining (80%) in stage 2 of
      voiding. CONCLUSIONS: Stomach seems to be an ideal source of material for bladder
      augmentation or replacement. The high capacity, low pressure reservoir provided
      by gastric tissue is probably due to the nature of the involuntary contractions,
      which occur only late in filling with a low amplitude. Also, the gastric
      neobladder is evacuated mainly by contraction of its musculature, supplemented
      with abdominal straining at the end of voiding.

PMID- 10210378
TI  - Immunocyt: a new tool for detecting transitional cell cancer of the urinary
      tract.
AB  - PURPOSE: The limitations of cytology and the invasiveness of cystoscopy for
      detecting bladder cancer generate increasing interest in noninvasive, urine bound
      diagnostic tools. We assessed the diagnostic value of the newly developed
      immunocytochemical test, Immunocyt, which detects cellular markers specific for
      transitional cell cancer in the voided urine of patients with bladder cancer.
      MATERIALS AND METHODS: Participating in our prospective study were 264
      consecutive patients with a mean age of 65.9 years, including 114 in whom
      symptoms were suggestive of bladder cancer and 150 who were being followed after
      complete transurethral resection of superficial transitional cell carcinoma.
      Voided urine specimens were evaluated by standard cytology and the Immunocyt
      test, which traces the monoclonal antibodies M344, LDQ10 and 19A211 against
      transitional cell carcinoma in exfoliated urothelial cells. In all cases
      cystoscopy was subsequently performed and any suspicious lesion was evaluated by
      biopsy. RESULTS: Histologically proved transitional cell carcinoma was found in
      79 patients. Immunocyt with cytology had 89.9% sensitivity overall (84, 88 and
      96.5% in grades 1 to 3 disease, respectively). A total of 34 (43%), 3 (3.8%) and
      34 (43%) cases were positive on Immunocyt only, cytology only and both
      evaluations, respectively. In 8 cases (10.1%) both tests were negative. Overall
      Immunocyt only was 86.1% sensitive (84, 84 and 89.6% in grades 1 to 3 disease,
      respectively) and 79.4% specific. Overall cytology only was 46.8% sensitive (4,
      52 and 79.3% in grades 1 to 3 disease, respectively) and 98.2% specific.
      CONCLUSIONS: Immunocyt is a noninvasive, highly sensitive test for detecting
      transitional cell carcinoma of all grades and stages. When combined with
      conventional urinary cytology, it may replace cystoscopy in select patients,
      especially in followup protocols of low grade transitional cell carcinoma.

PMID- 10210379
TI  - Intravesical chemotherapy with epirubicin: a dose response study.
AB  - PURPOSE: We determined the difference in response to high and standard doses of
      intravesical epirubicin for treatment of superficial bladder cancer. MATERIALS
      AND METHODS: A total of 122 patients were entered into a randomized trial to
      compare the response of a marker tumor at 3 months, time to first recurrence and
      recurrence rates for 2 years after intravesical chemotherapy for superficial
      (pTa/pT1) bladder cancer. Patients were randomized to receive treatment for 1
      hour with 1 (standard dose) or 2 mg./ml. (high dose) epirubicin (50 or 100 mg./50
      ml. solution). RESULTS: There was no difference in the marker tumor response rate
      in 24 of 52 patients treated with the standard dose compared with 21 of 50
      treated with the higher dose of epirubicin (p = 0.67). Similarly, the higher dose
      was not superior in regard to time to first recurrence, with a hazard ratio of
      1.46 (p = 0.14, 95% confidence intervals 0.88 to 2.42). Considering the upper end
      of the confidence interval, we can reliably exclude an absolute difference of
      greater than 4% at 1 year for time to first recurrence in favor of higher dose
      chemotherapy. CONCLUSIONS: Epirubicin at double the standard dose for
      intravesical chemotherapy of superficial bladder cancer is not superior in regard
      to marker tumor response, time to first recurrence or recurrence rate.

PMID- 10210380
TI  - Prognostic factors of outcome after radical cystectomy for bladder cancer: a
      retrospective study of a homogeneous patient cohort.
AB  - PURPOSE: Pathological predictors of outcome for patients undergoing radical
      cystectomy for bladder cancer are needed as few data are available in the
      literature. We retrospectively analyzed a homogeneous and contemporary series of
      patients treated with radical surgery as monotherapy for bladder cancer to
      identify the independent predictors of survival. MATERIALS AND METHODS: We
      evaluated 369 of 535 patients with bladder cancer treated with radical
      cystectomy, pelvic node dissection and urinary diversion by the same staff at a
      single institution between February 1982 and February 1994. Patients treated with
      radiation therapy and/or chemotherapy, and those who did not undergo formal
      pelvic node dissection were excluded from study. The end point of univariate and
      multivariate analyses was the overall 5-year survival. RESULTS: Univariate
      analysis revealed that tumor stage, nodal involvement, ureteral obstruction, and
      vascular, lymphatic and perineural invasion were prognostic predictors of
      survival (p <0.05). However, only tumor stage (p <0.0000) and nodal involvement
      (p <0.0000) were independent prognostic variables of survival on multivariate
      analysis. CONCLUSIONS: Tumor stage and nodal involvement are the only independent
      predictors of survival to be used to select the optimal therapy after radical
      cystectomy, stratify patients in controlled trials and evaluate new prognostic
      factors.

PMID- 10210381
TI  - Perineal subcutaneous dartos pedicled flap as a new technique for repairing
      urethrorectal fistula.
AB  - PURPOSE: Urethrorectal fistulas are rare, and the etiology is usually traumatic
      or iatrogenic (postoperative). Several operative approaches and techniques have
      been used for fistulous repair but no procedure has proved to be the best or
      universally acceptable. We present a new technique for repairing urethrorectal
      fistulas. MATERIALS AND METHODS: We successfully treated 12 male patients 7 to 65
      years old who presented with urethrorectal fistula from 1990 to 1997 using the
      perineal subcutaneous dartos pedicled flap procedure. Urethrorectal fistulas
      resulted from crush pelvic injury in 6 cases and gunshot in 2, and developed
      after prostatectomy in 4. The fistula was associated with urethral stricture in 4
      cases. A perineal approach was used in all cases of urethrorectal fistula and
      combined with the transsymphyseal approach in the 4 patients with posterior
      urethral stricture. We interposed a subcutaneous dartos pedicled flap as a
      vascularized tissue flap between the repaired rectum and urethra. RESULTS: The
      results of our technique were excellent in all cases. No leakage or perineal
      collection developed and there was no fistula recurrence. In 1 patient urethral
      stricture was managed by visual internal urethrotomy. Loss of the internal and
      external sphincters resulted in urinary incontinence in 4 cases, involving
      gunshot injury (2), crush pelvic injury (1) and prostatectomy (1). Followup
      ranged from 9 to 42 months. CONCLUSIONS: Our technique of a perineal subcutaneous
      dartos pedicled flap fulfills all principles of the successful repair of
      urethrorectal fistula. We consider it to be an ideal solution to this urological
      dilemma.

PMID- 10210382
TI  - Buccal mucosa urethroplasty for the treatment of bulbar urethral strictures.
AB  - PURPOSE: We report the results of urethroplasty with a free graft of buccal
      mucosa as a dorsal onlay for the treatment of bulbar urethral strictures.
      MATERIALS AND METHODS: Since June 1994, 30 patients with bulbar urethral
      strictures have been treated with buccal mucosa urethroplasty. Urethroplasty was
      performed with a free graft of buccal mucosa using a ventral onlay in the first 7
      patients and a dorsal onlay in 23. Dorsal urethrotomy was performed with a Sachse
      urethrotome after the bulbar urethra was separated from the corpora. The buccal
      mucosa onlay was sutured to the urethra and corpora cavernosa to ensure a patent
      urethra. RESULTS: At 20-month followup (range 3 to 50) the success rate was 96%
      (29 of 30 patients). Urethral stricture recurred in only 1 of 7 patients in the
      ventral onlay and none of 23 in the dorsal onlay group. CONCLUSIONS: Preliminary
      results of urethroplasty for bulbar urethral strictures with a dorsal onlay graft
      of buccal mucosa are excellent. Longer followup is needed to evaluate definitive
      results.

PMID- 10210383
TI  - Quality of cryopreserved testicular sperm in patients with obstructive and
      nonobstructive azoospermia.
AB  - PURPOSE: Sperm retrieved by testicular sperm extraction is routinely used to
      attempt pregnancy by in vitro fertilization-intracytoplasmic sperm injection. We
      evaluated the efficacy of cryopreserving testicular sperm collected by testicular
      sperm extraction at diagnostic biopsy. MATERIALS AND METHODS: A total of 73 men
      with obstructive and 42 with nonobstructive azoospermia underwent testicular
      sperm extraction at diagnostic biopsy. Sperm was retrieved and cryopreserved in
      all cases of obstruction and in 15 of nonobstructive azoospermia cases. Before
      freezing we determined sperm count, motility, morphology and viability, and after
      thawing we assessed sperm motility and viability. In 17 couples a total of 20
      cycles of in vitro fertilization-intracytoplasmic sperm injection were performed
      and fertilization, cleavage and pregnancy rates were determined in cases of
      obstruction and nonobstruction. RESULTS: Sperm count and morphology were lower in
      the testicular biopsies of men with nonobstructive versus obstructive
      azoospermia. Motility was low or absent in all testicular sperm extraction
      specimens. Importantly, pre-freeze (63%) and post-thaw (31%) viability was the
      same in both patient groups. After in vitro fertilization-intracytoplasmic sperm
      injection using frozen and thawed testicular sperm the fertilization, cleavage,
      implantation and clinical pregnancy rates were 60, 86, 16 and 50%, respectively.
      Using cryopreserved sperm we observed no differences in outcome of any in vitro
      fertilization-intracytoplasmic sperm injection procedure in patients with
      obstructive versus nonobstructive azoospermia. CONCLUSIONS: Cryopreservation of
      testicular sperm provides enough good quality sperm after thawing to result in
      excellent in vitro fertilization-intracytoplasmic sperm injection outcomes.
      Cryopreservation does not adversely affect intracytoplasmic sperm injection
      outcomes, including pregnancy rate. Therefore, we recommend routine testicular
      sperm extraction and cryopreservation of sperm at testicular biopsy.

PMID- 10210384
TI  - Urinary flow rate recording: the impact of a single dose of a diuretic on clinic
      logistics and flow rate parameters.
AB  - PURPOSE: We determine the impact of a single dose of a diuretic given to patients
      scheduled for flow rate recording on clinic waiting time and flow rate
      parameters, and whether such practice induces artifacts in recording independent
      of those inherent in repeat recordings. MATERIALS AND METHODS: A total of 99
      volunteers with a mean age plus or minus standard deviation of 54 +/- 10.9 years
      with no known urological condition participated in an open label, crossover
      study. On 2 separate occasions they came to the clinic for a flow rate recording,
      and were randomized to receive 20 mg. furosemide upon arrival at the first or
      second visit. Clinic waiting time, pre-void bladder volume, voided volume,
      maximum flow rate and other parameters were captured in a database and analyzed.
      RESULTS: Independent of diuretic use an increase in voided volume and maximum
      flow rate (19.8 to 21.2 ml. per second) was noted from the first to second visit.
      Diuretic use independent of sequence induced an increase in voided volume and
      significant reduction in waiting time (155 versus 81 minutes, p <0.001) without
      affecting maximum flow rate (19.9 versus 21.1 ml. per second, p = 0.058).
      Diuretic use on the second visit enhanced the learning effect on maximum flow
      rate, while first visit use negated the learning effect on the second visit.
      Waiting time reduction was significant independent of sequence. The positive
      correlation between voided volume and maximum flow rate remained unchanged with
      or without the diuretic. CONCLUSIONS: Repeat flow rate recordings are associated
      with a measurable learning effect leading to an increase in maximum flow rate.
      The use of 20 mg. furosemide reduces waiting time without inducing additional
      artifacts or significant changes in flow rate parameters. This practice is
      recommended for busy offices or clinical research centers to enhance urine flow,
      patient satisfaction and ultimately compliance with care.

PMID- 10210385
TI  - Improvement of pressure flow parameters with finasteride is greater in men with
      large prostates. Finasteride Urodynamics Study Group.
AB  - PURPOSE: We assess the effect of finasteride, a 5alpha-reductase inhibitor, on
      objective voiding parameters in men with lower urinary tract symptoms and benign
      prostatic enlargement on digital rectal examination (known as clinical benign
      prostatic enlargement) in a double-blind placebo controlled multicenter study
      using strict standard pressure flow study techniques. MATERIALS AND METHODS: A
      modification of the Abrams-Griffiths nomogram was used by 1 reader to ensure that
      all patients met objective criteria for bladder outlet obstruction at baseline.
      After performing a pressure flow study patients with obstruction were randomized
      2:1 to receive 5 mg. finasteride (81) or placebo (40) daily. A second pressure
      flow study was performed at month 12. At baseline and month 12 free urinary flow
      studies and transrectal ultrasound were performed, and International Prostate
      Symptom Score questionnaires were completed. Patients were treated between May
      1994 and July 1996. RESULTS: Finasteride caused a significant decrease (-8.1 cm.
      water) in detrusor pressure at maximum flow (p <0.05 versus placebo p = 0.02),
      increase (+1.1 ml. per second) in maximum flow rate (p <0.05 versus placebo p =
      0.02) and decrease (-22.8%) in prostate volume (p <0.05 versus placebo p <0.001).
      Men with prostates larger than 40 cc had greater improvement in detrusor pressure
      at maximum flow (between group difference -14.5 cm. water, 95% confidence
      interval -26.2 to -2.6, p = 0.02) and maximum flow rate (mean treatment effect
      +1.6 ml. per second, 95% confidence interval -0.2 to 3.0, p = 0.02) compared to
      those with prostates 40 cc or less (between group differences not significant).
      CONCLUSIONS: Finasteride treatment resulted in improvements in urodynamic
      parameters, which were greater in men with large prostates.

PMID- 10210386
TI  - Rectourinary fistula repair using the Latzko technique.
AB  - PURPOSE: We report our experience with the Latzko technique for rectourinary
      fistula repair after radical retropubic prostatectomy and cystoprostatectomy.
      MATERIALS AND METHODS: We performed 7 fistula repairs in 6 patients. The 1-stage
      procedure was based on a technique for vesicovaginal fistula closure with
      denudation of the rectal mucosa and multilayer closure of the fistulous tract.
      RESULTS: Closure was successful in all patients, although 1 had to undergo the
      procedure twice. There were no postoperative complications. CONCLUSIONS: The
      Latzko procedure is effective for rectourinary fistula repair and associated with
      minimal morbidity.

PMID- 10210387
TI  - Prevalence and patterns of the use of complementary therapies among prostate
      cancer patients: an epidemiological analysis.
AB  - PURPOSE: We determine the prevalence and patterns of the use of complementary
      therapies among patients with and those at high risk for prostate cancer.
      MATERIALS AND METHODS: A cross-sectional survey was performed of men presenting
      to 2 urban tertiary urology clinics for prostate cancer evaluation or followup,
      and those attending a prostate cancer support group. All men diagnosed with and
      those at high risk (positive family history or abnormal prostate specific
      antigen) for prostate cancer were eligible for study. A 9-item self-administered,
      anonymous questionnaire about complementary therapies was administered. RESULTS:
      Of 357 patients who received the survey 155 from the urology clinics and 113 from
      the support group responded, for a total response rate of 75%. Of the patients
      presenting to urology clinics and the support group 27.4 and 38.9% with and 25.8
      and 80% at high risk for prostate cancer, respectively, used some form of
      complementary therapy. The use significantly differed according to disease status
      (p = 0.001), and was highest among men who were clinically disease-free after
      radical therapy. Of the patients 24% did not inform the urologist of using
      alternative therapy. CONCLUSIONS: The prevalence of the use of complementary
      therapy among patients with or at increased risk for prostate cancer was high and
      dependent on the disease state. Urologists should be aware of this pattern of
      use, and consider the potential effects when assessing patients for and with
      prostate cancer.

PMID- 10210388
TI  - Clinical and pathological characteristics, and recurrence rates of stage T1c
      versus T2a or T2b prostate cancer.
AB  - PURPOSE: We compare clinicopathological features, and cancer recurrence and
      survival rates in men with stage T1c versus T2a or T2b prostate cancer. MATERIALS
      AND METHODS: From 1988 through 1998, 1 surgeon (W. J. C.) performed radical
      retropubic prostatectomy in 1,620 men with a mean age plus or minus standard
      deviation of 62.3 +/- 7 years. Clinical stage was T1c in 39%, T2a in 22% and T2b
      in 39% of patients. Patients were followed with semiannual prostate specific
      antigen (PSA) measurement and annual digital rectal examination. Serum total PSA
      greater than 0.3 ng./ml., histologically confirmed local tumor recurrence or
      distant metastases were considered evidence of cancer recurrence. Simple
      univariate statistics were used to compare clinical and pathological features by
      clinical stage, and multivariate Cox models were used to compare 5-year
      recurrence-free probabilities . The 5-year all cause and disease specific
      survival rates were calculated using Kaplan-Meier product limit estimates.
      RESULTS: Mean patient age was younger for the clinical stage T1c group (61 years)
      than for the T2a (62 years) or T2b (64 years) group. Mean preoperative PSA and
      the percentage of patients with biopsy Gleason score 8 to 10 were more favorable
      for the T1c (8 ng./ml., 3%) and T2a (7, 5%) groups than for the T2b group (11,
      6%). Cancerous surgical margins, seminal vesicle invasion and lymph node
      metastases were also less frequent in the T1c (20, 5 and 0.8%, respectively) and
      T2a (23, 5 and 0.3%) groups than in the T2b group (29, 11 and 1.8%). The 5-year
      recurrence-free survival rate was 85% for T1c, 83% for T2a and 72% for T2b cases.
      Multivariate analysis indicated a decreased risk of recurrence for the T1c group
      compared to the T2a and T2b groups. The 5-year disease specific survival rate was
      100% for the T1c and T2a groups, and 97% for the T2b group. CONCLUSIONS: Clinical
      and pathological features were similar for stages T1c and T2a, and different from
      stage T2b cancers. The 5-year recurrence-free survival was similar for T1c and
      T2a (log rank 0.89, p = 0.34), and higher than that for T2b (log rank 34.5, p
      <0.0001) cancers. However, controlling for all other prognostic factors on a Cox
      multivariate model, the risk of cancer recurrence was decreased for T1c compared
      to T2a and T2b disease. The detection of nonpalpable prostate cancer appears to
      be advantageous for intermediate-term cancer control.

PMID- 10210389
TI  - A 3 trocar technique for transperitoneal laparoscopic nephrectomy.
AB  - PURPOSE: Additional trocars and retractor instruments may enhance the risk of
      iatrogenic injuries during laparoscopic nephrectomy. We describe a modified
      technique of laparoscopic nephrectomy requiring only 3 ports of entry and no
      extra instruments instead of the 5 ports, 2 of which are used for retractors,
      usually required. MATERIALS AND METHODS: With the patient in full flank position
      a 10 mm. trocar is inserted between the umbilicus and subcostal margin, a 5 mm.
      trocar is placed subcostal in the midclavicular line and a 12 mm. trocar is
      inserted over the iliac crest in the anterior axillary line. The first step is
      incision of the line of Toldt and medial reflection of the colon. During the
      second step of vascular controls the posterosuperior attachments of the kidney
      are left untouched, keeping the renal vessels stretched, with no need for an
      extra instrument. The third step consists of severing the remaining posterior and
      superior attachments of the kidney followed by specimen retrieval. A total of 14
      consecutive patients underwent laparoscopic nephrectomy with this technique.
      RESULTS: All 14 procedures were completed without an additional port. There were
      no intraoperative or postoperative complications, except 1 abdominal wall
      hematoma. Mean operating time was 120 minutes (range 70 to 230) and mean hospital
      stay was 5 days (range 3 to 7). CONCLUSIONS: Transperitoneal laparoscopic
      nephrectomy with laparoscopic access limited to 3 trocars is a reliable and safe
      technique.

PMID- 10210390
TI  - An easy and safe approach to separating Denonvilliers' fascia from rectum during
      radical retropubic prostatectomy.
AB  - PURPOSE: We describe a simple technique for excising Denonvilliers' fascia during
      nonnerve sparing radical retropubic prostatectomy. MATERIALS AND METHODS: After
      incision of the perirectal fascia Denonvilliers' fascia is bluntly mobilized off
      of the rectum digitally and by using an aortic clamp. RESULTS: This technique was
      used successfully in 200 consecutive cases of nonnerve sparing radical retropubic
      prostatectomy since 1994 with no rectal injuries. CONCLUSIONS: This procedure
      guarantees simple and complete excision of Denonvilliers' fascia, which covers
      the posterior surface of the prostate during nonnerve sparing radical retropubic
      prostatectomy.

PMID- 10210391
TI  - Diagnosing bladder outlet obstruction in women.
AB  - PURPOSE: There are no universally accepted urodynamic criteria for diagnosing
      female bladder outlet obstruction. When accepted criteria for men are applied to
      women, the diagnosis of obstruction may often be missed, which is most likely due
      to differences in voiding dynamics. We propose video urodynamic criteria for
      diagnosing obstruction in women, and describe the urodynamic findings in those
      with and without obstruction. MATERIALS AND METHODS: We reviewed the charts of
      331 women who underwent multichannel video urodynamics for nonneurogenic voiding
      dysfunction. Of these women 261 (mean age 55.8 years) had evaluable voiding
      pressure flow studies with simultaneous video fluoroscopy of the bladder outlet
      during voiding. At video urodynamics cases were classified as obstructed if there
      was radiographic evidence of obstruction between the bladder neck and distal
      urethra in the presence of a sustained detrusor contraction. Strict pressure flow
      criteria were not used. Maximum flow rate, detrusor pressure at maximum flow
      rate, post-void residual, bladder capacity and the incidence of detrusor
      instability were compared between obstructed and unobstructed cases. RESULTS: A
      total of 76 women met the criteria for obstruction (mean age 57.5 years), while
      184 (mean age 55) did not. Causes of obstruction were dysfunctional voiding in 25
      cases, cystocele in 21, primary bladder neck obstruction in 12, iatrogenic from
      incontinence surgery in 11, urethral stricture in 3, uterine prolapse in 2,
      urethral diverticulum in 1 and rectocele in 1. Obstructed cases had lower mean
      maximum flow rate (9 versus 20.2 ml. per second, p <0.0001), higher mean detrusor
      pressure at maximum flow rate (42.8 versus 22.1 cm. water, p <0.0001) and higher
      mean post-void residual (157 versus 33 ml., p <0.0001). There was no difference
      in bladder capacity (381 versus 347 ml.) or incidence of detrusor instability (45
      versus 41%). CONCLUSIONS: Using the proposed video urodynamic criteria obstructed
      cases had significantly higher voiding pressures, lower flow rates and higher
      post-void residual than unobstructed cases, as expected. However, absolute
      values, especially for voiding pressure, are not as dramatic in women as in men.
      Pressure flow studies alone may fail to diagnose obstruction but simultaneous
      imaging of the bladder outlet during voiding greatly facilitates diagnosis.

PMID- 10210392
TI  - A provocative maneuver to elicit cystometric instability: measuring instability
      at maximum infusion.
AB  - PURPOSE: We identify a provocative maneuver to enhance the sensitivity of
      cystometry in detecting detrusor instability when urge incontinence is suspected
      based on clinical history. MATERIALS AND METHODS: A total of 134 consecutive
      women with clinical urge incontinence underwent carbon dioxide cystometry between
      August 1995 and October 1996. The bladder was filled to maximal capacity with the
      patient supine. Six provocative maneuvers were performed consecutively to evoke
      detrusor instability, including lying supine, rising to a seated position,
      walking toward the bathroom, handwashing, coughing and sitting on the toilet with
      instructions not to void. Subjects were divided into 2 groups depending on the
      order of maneuvers. Sitting on the toilet was the last maneuver for group 1 (80
      patients) and was in the middle of the sequence for group 2 (54). RESULTS:
      Sitting on the toilet evoked detrusor instability in 37.5% of group 1 and 53.8%
      of group 2. This maneuver with instructions not to void was the most provocative
      stimulus in eliciting detrusor instability with a detection rate of 68.4% for all
      subjects. CONCLUSIONS: Sitting on the toilet with the bladder at maximal capacity
      is the most provocative maneuver for detecting detrusor instability. The
      incidence of suspected detrusor instability is enhanced by using this test during
      routine cystometry.

PMID- 10210393
TI  - Long-term followup of the North American multicenter UroLume trial for the
      treatment of external detrusor-sphincter dyssynergia.
AB  - PURPOSE: We determine the long-term efficacy and safety of the UroLume stent as
      minimally invasive treatment for external detrusor-sphincter dyssynergia in
      spinal cord injured men. MATERIALS AND METHODS: A total of 160 spinal cord
      injured men with a mean age plus or minus standard deviation of 36.3 +/- 12.1
      years (range 16 to 74) were prospectively treated with an endoprosthesis at 15
      centers as part of the North American UroLume trial for external detrusor
      sphincter dyssynergia. Urodynamic parameters, including voiding pressure,
      residual urine volume and bladder capacity, were compared before treatment and at
      1, 2, 3, 4 and 5 years after treatment. RESULTS: Mean voiding pressure was 75.1
      +/- 28.2 cm. water before treatment in the 160 patients, and 37.4 +/- 23.9 at
      year 1 in 97, 39.5 +/- 22.2 at year 2 in 84, 42.6 +/- 27.3 at year 3 in 61, 46.3
      +/- 33.2 at year 4 in 57 and 44.2 +/- 28.9 cm. at year 5 in 41 after stent
      insertion (p <0.001). Residual urine volume decreased after stent placement and
      was maintained throughout the 5-year followup (p <0.001). Mean cystometric
      capacity remained constant from 269 +/- 155 before insertion to 337 +/- 182 ml. 5
      years later (p = 0.17). Hydronephrosis and autonomic dysreflexia improved or
      stabilized in most patients with functioning stents. Stent explant was necessary
      in 24 patients (15%), of whom 4 (16.7%) had another stent implanted. CONCLUSIONS:
      The UroLume stent demonstrates long-term safety and efficacy for the treatment of
      external detrusor-sphincter dyssynergia. The outcome was similar in men with and
      without previous sphincterotomy.

PMID- 10210394
TI  - Clinical efficacy and safety of tolterodine compared to placebo in detrusor
      overactivity.
AB  - PURPOSE: We evaluated the efficacy, patient acceptability and side effect profile
      of tolterodine, a new antimuscarinic agent for treating bladder overactivity.
      MATERIALS AND METHODS: In our randomized, placebo controlled, parallel group
      study 123, 129 and 64 patients 18 years old or older with proved detrusor
      overactivity (idiopathic detrusor instability or detrusor hyperreflexia) were
      randomized to receive 1 or 2 mg. tolterodine, or placebo, respectively, twice
      daily for 12 weeks. Main outcome measures were number of voids per 24 hours,
      urine volume per void and episodes of urge incontinence per 24 hours on a
      frequency-volume chart with detailed recording of side effects. RESULTS: After 12
      weeks of treatment mean number of voids per 24 hours plus or minus standard
      deviation decreased from 11.2 +/- 3.1 to 9.0 +/- 2.6 with the 2 mg. dosage (p =
      0.0045 versus placebo). At this dose mean urine volume per void increased from
      155 +/- 52 to 190 +/- 70 ml. (p <0.0001 versus placebo), while mean number of
      incontinence episodes per 24 hours decreased from 3.6 +/- 4.0 to 1.8 +/- 3.1 (p =
      0.19 versus placebo). Similar efficacy was observed in patients receiving the 1
      mg. dose. Severe dry mouth was reported by only 2, 1 and 2% of patients given the
      1 and 2 mg. dose, and placebo, respectively. There was no clinical or
      electrocardiographic evidence of significant cardiac adverse events. CONCLUSIONS:
      Tolterodine administration resulted in a significant decrease in the frequency of
      voiding and improved voided volume but it was seldom associated with troublesome
      or severe side effects.

PMID- 10210395
TI  - Bladder dysfunction--challenges for the new millennium.

PMID- 10210396
TI  - Primary bilateral hydatidosis of the psoas muscle.

PMID- 10210397
TI  - Laparoscopic heminephrectomy of a horseshoe kidney using microwave coagulator.

PMID- 10210398
TI  - Endopyelotomy for treatment of ureteropelvic junction obstruction caused by
      torsion of a renal allograft.

PMID- 10210399
TI  - Drainage vein of left renal cell carcinoma communicating with inferior mesenteric
      vein.

PMID- 10210400
TI  - Repair of ureteral gunshot injury with appendiceal interposition.

PMID- 10210401
TI  - Simple melanosis of the bladder.

PMID- 10210402
TI  - Granulocyte colony-stimulating factor and parathyroid hormone related protein
      producing bladder cancer.

PMID- 10210403
TI  - Leukocytosis associated with and localized bladder cancer: resolution with
      radiation therapy.

PMID- 10210404
TI  - Severe bacillus Calmette-Guerin cystitis responds to systemic steroids when
      antituberculous drugs and local steroids fail.

PMID- 10210405
TI  - Parathyroid hormone related protein and carcinoma of the penis: paraneoplastic
      hypercalcemia.

PMID- 10210406
TI  - Leydig cell tumors presenting as azoospermia.

PMID- 10210407
TI  - Testicular teratoma in a man with XX/XXY mosaic Klinefelter's syndrome.

PMID- 10210408
TI  - Malignant large cell calcifying sertoli cell tumor with endocrine overactivity.

PMID- 10210409
TI  - Perineal fistulization of genital tuberculosis.

PMID- 10210410
TI  - Basic scientists in urology departments.

PMID- 10210412
TI  - Re: Renal medullary carcinoma.

PMID- 10210411
TI  - Re: A case of Cushing's syndrome due to adrenocortical carcinoma with recurrence
      19 months after laparoscopic adrenalectomy. Re: Re: A case of Cushing's syndrome
      due to adrenocortical carcinoma with recurrence 19 months after laparoscopic
      adrenalectomy.

PMID- 10210413
TI  - Re: The role of urinary potassium in the pathogenesis and diagnosis of
      interstitial cystitis.

PMID- 10210414
TI  - Re: Lack of evidence for a role of human papillomaviruses in transitional cell
      carcinoma of the bladder.

PMID- 10210415
TI  - Re: Results of a randomized phase III trial of sequential intravesical therapy
      with mitomycin C and bacillus Calmette-Guerin versus mitomycin C alone in
      patients with superficial bladder cancer.

PMID- 10210416
TI  - Re: Treatment of male urethral strictures: is repeated dilation or internal
      urethrotomy useful?

PMID- 10210417
TI  - Re: Reactive oxygen species production by the spermatozoa of patients with
      idiopathic infertility: relationship to seminal plasma antioxidants.

PMID- 10210418
TI  - Re: Editorial: benign prostatic hyperplasia--from bench to bedside.

PMID- 10210419
TI  - Re: Use of lower prostate specific antigen cutoffs for prostate cancer screening
      in black and white men.

PMID- 10210420
TI  - Re: Biological aggressiveness of hereditary prostate cancer: long-term evaluation
      following radical prostatectomy.

PMID- 10210421
TI  - Feminizing genitoplasty for congenital adrenal hyperplasia: what happens at
      puberty?
AB  - PURPOSE: We document the postpubertal outcome of feminizing genitoplasty.
      MATERIALS AND METHODS: A total of 14 girls, mean age 13.1 years, with congenital
      adrenal hyperplasia were assessed under anesthesia by a pediatric urologist,
      plastic/reconstructive surgeon and gynecologist. Of these patients 13 had
      previously undergone feminizing genitoplasty in early childhood at 4 different
      specialist centers in the United Kingdom. RESULTS: The outcome of clitoral
      surgery was unsatisfactory (clitoral atrophy or prominent glans) in 6 girls,
      including 3 whose genitoplasty had been performed by 3 different specialist
      pediatric urologists. Additional vaginal surgery was necessary for normal
      comfortable intercourse in 13 patients. Fibrosis and scarring were most evident
      in those who had undergone aggressive attempts at vaginal reconstruction in
      infancy. CONCLUSIONS: These disappointing results, even in the hands of
      specialists, highlight the importance of late followup and challenge the
      prevailing assumption that total correction can be achieved with a single stage
      operation in infancy. Although simple exteriorization of a low vagina can
      reasonably be combined with cosmetic correction of virilized external genitalia
      in infancy, we now believe that in some cases it may be best to defer definitive
      reconstruction of the intermediate or high vagina until after puberty. The
      psychological issues surrounding sexuality in these patients are inadequately
      researched and poorly understood.

PMID- 10210422
TI  - Feminizing genitoplasty.

PMID- 10210423
TI  - T-type pelvis with separate kidneys associated with complete duplication of the
      ureter in a male infant with the prune belly syndrome.

PMID- 10210424
TI  - Hyperbaric oxygen therapy for pediatric hemorrhagic cystitis.

PMID- 10210425
TI  - Urinary continence after staged bladder reconstruction for cloacal exstrophy: the
      effect of coexisting neurological abnormalities on urinary continence.
AB  - PURPOSE: We determined whether there is a difference in the incidence of urinary
      continence in cloacal and classic bladder exstrophy after staged bladder neck
      reconstruction using the Young-Dees-Leadbetter technique. MATERIALS AND METHODS:
      We reviewed the records of patients with cloacal and classic bladder exstrophy
      who underwent staged bladder neck reconstruction from 1971 to 1997. RESULTS: The
      Young-Dees-Leadbetter bladder neck reconstruction was completed in 23 patients
      with cloacal exstrophy, of whom 5 (22%) became continent and 18 (78%) have
      persistent incontinence. A clinically apparent neurological abnormality
      significantly hindered the achievement of continence. Specifically 1 of the 13
      children (7%) with versus 4 of the 10 (40%) without a neurological abnormality
      became continent (p <0.05). In contrast, staged reconstruction of classic bladder
      exstrophy resulted in urinary continence in 67 of the 82 patients (82%). Of the
      67 continent patients 23 (34%) cannot void and require intermittent
      catheterization. None of the patients with classic exstrophy had a neurological
      deficit. CONCLUSIONS: The ability of the Young-Dees-Leadbetter bladder neck
      reconstruction to result in urinary continence significantly differs in the
      cloacal and classic bladder exstrophy populations (22 versus 82%, p <0.001). Our
      findings also suggest that a coexisting neurological abnormality significantly
      hinders the ability to reconstruct a functional bladder in patients with cloacal
      exstrophy.

PMID- 10210426
TI  - Arterial supply of the human fetal testis during its migration.
AB  - PURPOSE: Irrespective of the surgical technique chosen to treat high undescended
      testis, preservation of an adequate arterial supply for the testis is crucial for
      successful orchiopexy with maintenance of normal testicular size and texture. To
      provide an anatomical background for such a procedure, we performed a systematic
      study on the number and origin of arteries supplying the fetal testis during its
      migration from the abdomen to the scrotum. MATERIALS AND METHODS: We studied
      bilaterally 64 testes from 32 fresh human fetuses 13 to 33 weeks after
      conception. The fetuses were injected through the thoracic aorta with a
      microvascular silicone rubber red resin to fill in the arterial tree, thereby
      enabling identification and dissection of all arteries supplying the testes.
      RESULTS: Of the 64 testes 3 arteries (testicular, deferential and cremasteric)
      were found in 46 (71.9%), 2 (testicular and deferential) in 15 (23.4%) and 4 in 3
      (4.7%). CONCLUSIONS: The fetal testis is always supplied by at least 2 arteries
      (testicular and deferential arteries) and by 3 or 4 arteries in nearly 80% of the
      cases.

PMID- 10210427
TI  - Risk factors for cryptorchidism and hypospadias.
AB  - PURPOSE: We studied risk factors for cryptorchidism and hypospadias. MATERIALS
      AND METHODS: We performed a register based, case control study of 6,177 boys with
      cryptorchidism, 1,345 with hypospadias and 23,273 male controls born live in
      Denmark from 1983 to 1992 to determine the effects of cryptorchidism and
      hypospadias on the presence of the other abnormality in an individual, the
      presence of the abnormalities in an older brother, birth weight, weeks of
      gestation, maternal history of stillbirth, parity, twin birth, parental age,
      nationality and professional status. Unconditional logistic regression analysis
      was used to estimate odds ratios. RESULTS: In an individual simultaneous
      cryptorchidism and hypospadias were more common than expected. There was an
      increased risk of both entities when the same abnormality was present in an older
      brother. The risk of cryptorchidism and hypospadias increased with decreasing
      birth weight independent of weeks of gestation. Twins were at lower risk than
      singletons for both entities in all lower birth weight groups. An increased risk
      of hypospadias was noted in the sons of women who had had a previous stillbirth.
      The risk of cryptorchidism and hypospadias slightly increased with decreasing
      parity. CONCLUSIONS: Birth weight was the principal determinant of cryptorchidism
      and hypospadias. Twins were at lower risk for both abnormalities than singletons
      in the same birth weight classes. There are indications of separate genetic as
      well as common environmental causes of cryptorchidism and hypospadias.

PMID- 10210428
TI  - Anatomy of ureterovesical junction and distal ureter studied by endoluminal
      ultrasonography in vitro.
AB  - PURPOSE: The emerging technique of endoluminal ultrasonography (ELUS) provides a
      new modality for endoscopic visualization of the urinary tract which needs to be
      further evaluated. We studied the normal anatomy of distal ureter and
      ureterovesical junction using ELUS. MATERIALS AND METHODS: An assessment of in
      vitro ELUS ureteric images undertaken at 1 mm. intervals from 8 fresh human
      cadaver pelvis blocs of bladder and distal ureter were compared with findings of
      serial histological sections of the same specimens (stained for cholinesterase
      isoenzymes) to assess the degree of correlation. Computer-assisted 3D
      reconstructions were made. RESULTS: The different components (ureteric, detrusor
      and periureteric tissue) of the UVJ could be identified on the basis of
      echogenicity and form, but differentiation between the respective muscle layers
      in the wall of the ureter or of the detrusor was not possible. Nevertheless,
      ureteric volume measurements and an assessment of transmural ureteric length and
      the angle of passage through the bladder wall were possible. CONCLUSIONS: ELUS is
      able to differentiate between the ureteric and detrusor muscle and the UVJ gross
      anatomy can be reconstructed. ELUS technology, however, fails to differentiate
      between individual muscular layers of the ureter or the detrusor. Further
      improvement in ELUS is mandatory.

PMID- 10210429
TI  - Testosterone induces vascular endothelial growth factor synthesis in the ventral
      prostate in castrated rats.
AB  - PURPOSE: Recent studies suggest that the vasculature is important for the control
      of prostate growth. Castration induces an involution of the prostate gland and
      its vasculature. Replacement of testosterone stimulates endothelial cell
      proliferation and normalizes vascular volumes and blood flow several days before
      organ regrowth. Antiangiogenesis treatment inhibits the growth of prostate
      tumors. Understanding the regulation of the prostate vasculature may therefore
      provide important knowledge of the mechanisms responsible for the growth of non
      malignant and malignant prostate tissue. Castration induced regression and
      testosterone stimulated regrowth of the prostatic vasculature have here been used
      to study the involvement of the angiogenic factor vascular endothelial growth
      factor (VEGF) and its receptors flt-1 and flk-1/KDR in the regulation of the
      prostatic vasculature. MATERIALS AND METHODS: VEGF, flt-1, and flk-1/KDR levels
      were quantified in the rat ventral prostate following castration and testosterone
      replacement. Methods used were competitive RT-PCR, Western blot and
      immunohistochemistry. RESULTS: VEGF mRNA and protein levels were significantly
      decreased by castration and testosterone treatment induced VEGF synthesis in the
      rat ventral prostate epithelium. Flt-1 and flk-1/KDR receptor levels were
      unaffected by castration and testosterone treatment. CONCLUSIONS: Castration down
      regulates VEGF and testosterone induces VEGF synthesis in epithelial cells in the
      rat ventral prostate.

PMID- 10210430
TI  - Atherosclerosis-induced chronic ischemia causes bladder fibrosis and non
      compliance in the rabbit.
AB  - PURPOSE: The overall goal was to determine whether chronic ischemia and
      hypercholesterolemia interfere with bladder function and structure. The roles of
      atherosclerosis-induced chronic ischemia and hypercholesterolemia in bladder
      fibrosis and non-compliance were studied in the rabbit. The relationship between
      ischemia-induced changes in the expression of transforming growth factor-beta1
      (TGF-beta1) and basic fibroblast growth factor (bFGF) and the severity of bladder
      fibrosis was also investigated. MATERIALS AND METHODS: Male New Zealand White
      rabbits were divided into chronic bladder ischemia (CBI, n = 11),
      hypercholesterolemia (Hch, n = 8) and control (n = 8) groups. The CBI group
      underwent balloon endothelial injury of the iliac arteries and received a 0.5%
      cholesterol diet. The Hch group received a 0.5% cholesterol diet alone. The
      control group was placed on a regular diet. After 16 weeks, iliac artery and
      bladder wall blood flow measurements, cystometrograms (CMG) and aorto-iliac
      arteriograms were obtained in all animals. Iliac arteries and bladder tissues
      were processed for histological staining and computer-assisted histomorphometric
      image analysis. The expressions of TGF-beta1 and bFGF in bladder tissue were
      determined by immunohistochemical staining utilizing monoclonal antibodies.
      RESULTS: At 16 weeks, arteriography and histology showed significant diffuse
      atherosclerotic occlusive disease of the aorto-iliac arteries in the CBI group.
      Iliac artery and bladder wall blood flows were significantly decreased in the CBI
      group compared with the Hch and control groups. Atherosclerosis-induced CBI
      shifted the volume-pressure curve to the left and caused severe bladder fibrosis.
      Hypercholesterolemia also caused fibrosis and non-compliance but to a much lesser
      extent compared with those caused by CBI. In histomorphometry, the percentage of
      detrusor smooth muscle was moderately decreased in the Hch group and severely
      decreased in the CBI group compared with the control group. In
      immunohistochemical stains of bladder tissues, bFGF expression was similar in the
      three groups of animals. TGF-beta1 expression was significantly greater in
      bladder tissues from the CBI group compared with the Hch and control groups.
      CONCLUSIONS: Our studies show that atherosclerosis-induced chronic ischemia
      increases TGF-beta1 expression in the bladder leading to fibrosis, smooth muscle
      atrophy and non-compliance. Hypercholesterolemia also interferes with bladder
      structure and compliance but to a significantly lesser extent compared with CBI.
      Our studies suggest that arterial insufficiency and hypercholesterolemia, common
      aging-associated disorders, may play important roles in the pathophysiology of
      voiding dysfunction in the elderly.

PMID- 10210431
TI  - Ureteral gene transfer to porcine induced strictures using endourologic delivery
      of an adenoviral vector.
AB  - PURPOSE: Direct gene transfer to the ureter is an attractive approach to prevent
      restenosis after endourologic management of ureteral strictures. We therefore
      assessed the rationale for adenovirus-mediated gene transfer in the ureter in
      vitro and in vivo using a porcine model. MATERIALS AND METHODS: Primary cultures
      of porcine ureteral epithelial and stromal cells were infected with an adenoviral
      solution carrying a nucleus-targeted beta-Galactosidase (beta-Gal) reporter gene
      (6.5 10(8) pfu/ml.). In addition, in order to mimic the human clinical situation,
      we have devised a model of thermally-induced stricture in porcine ureter which
      produced tight fibrotic stenosis within 8 days. Using a purposely designed
      channelled balloon catheter prototype, these strictures were endoscopically
      dilated and then instilled with the same beta-Gal adenoviral construction.
      RESULTS: Application of recombinant adenovirus harboring a nucleus-targeted beta
      Gal reporter gene to cultured porcine urothelial and stromal cells resulted in
      high transduction efficiency of up to 99% and 84% respectively. Seven days after
      infection, X-Gal staining of the strictured ureters demonstrated transfection up
      to 2 mm. depth within the fibrosis, confirmed by polymerase chain reaction (PCR)
      analysis. Adjacent and distal spread of the virus was excluded by histochemistry
      (X-Gal staining) and PCR. CONCLUSION: This data represents the first report of
      adenovirus-mediated gene transfer to the ureter. It remained site specific by
      endourologic retrograde clinically applicable techniques.

PMID- 10210432
TI  - Function of M3 muscarinic receptors in the rat urinary bladder following partial
      outlet obstruction.
AB  - PURPOSE: Partial outlet obstruction of the rat urinary bladder leads to
      hypertrophy and alteration in contractility of the detrusor muscle involving
      changes in muscarinic receptors. m3 muscarinic receptor subtype has been known to
      play a predominant role in contractility of normal urinary bladder. The purpose
      of the present study was to assess the role of m3 receptors in contractility of
      the obstructed bladder. MATERIALS AND METHODS: In male rats, partial outlet
      obstruction of the urinary bladder was performed by surgically tying a 6-0 suture
      around the bladder neck, reducing the diameter of it by 2/3 of the original size.
      Four weeks after the surgery, the bladders were removed and thin strips were
      microdissected. Similarly, bladder strips from age matched unoperated normal rats
      were obtained. Sets of four strips from four normal or four obstructed rats were
      mounted in an in vitro multi-muscle chamber containing normal physiological
      solution at 37C. The tension responses evoked by optimal electrical field
      stimulation at 1, 10, 30, 50, and 100 Hz, and the contracture responses evoked by
      120 mM potassium and 0.01 to 300.0 microM carbachol were recorded using a Nicolet
      digital oscilloscope. Similar responses were recorded in different sets of four
      strips following exposure to 10 and 100 nM 4-DAMP, which is a muscarinic
      antagonist with a high affinity for m3 and m1 receptor subtypes. RESULTS: The
      obstructed bladders showed 119% increase in weight. In control physiological
      solution, the obstructed bladder strips did not show significant difference in
      electrically-evoked tension or carbachol contractures, but showed significantly
      lower potassium contractures compared with normal bladder strips. 4-DAMP at 10 to
      100 nM significantly reduced the electrically evoked tension responses by about
      the same degree in normal and obstructed bladders, without affecting the
      potassium contractures. It significantly increased the EC50 values for carbachol
      contractures in normal bladder, and to a significantly lesser extent in
      obstructed bladder. Schild plots using the Hill transformed EC50 values showed
      that the pA2 value for 4-DAMP was not significantly different in normal and
      obstructed bladders. CONCLUSIONS: Significantly smaller potassium contracture in
      the obstructed bladder indicates that depolarizability of the detrusor muscle
      membrane, and consequently the activity of voltage-gated Ca2+ channels may be
      reduced in the detrusor after partial outlet obstruction. Lack of a significant
      difference in the effect of 4-DAMP on the electrically evoked tension responses
      and in the pA2 values for 4-DAMP assessed by carbachol contractures, in normal
      and obstructed bladder strips, indicates that m3 muscarinic receptors still play
      a predominant role in causing detrusor contractility in the obstructed bladder,
      as in the normal bladder.

PMID- 10210433
TI  - Vitamin E inhibits the high-fat diet promoted growth of established human
      prostate LNCaP tumors in nude mice.
AB  - PURPOSE: Prostate cancer has become an important public health problem in the
      Western world. It is currently the most common diagnosed cancer and the second
      leading cause of cancer deaths among North American men. Prostate cancer
      possesses a unique descriptive epidemiology which suggests that environmental
      factors (such as dietary fat consumption) play a pivotal role in tumor
      progression. Data from our institution have demonstrated that diets high in fat
      content can accelerate the growth of human LNCaP prostate cancer cells. One of
      the hypothesized mechanisms of dietary fat induced growth is oxidative stress.
      Our purpose was to determine the effect of supplemental Vitamin E, a potent
      intracellular antioxidant, on the high-fat promoted growth of transplanted LNCaP
      cells in the athymic mouse. MATERIALS AND METHODS: Tumors were induced by
      subcutaneous injection of 10(6) LNCaP cells. Mice were fed a control diet
      consisting of 40.5% of total calories from dietary fat. Once tumors were formed,
      PSA values were obtained and animals were randomized into 4 groups of 12. The
      animals were then assigned to one of 4 dietary plans. Group 1 received the
      control diet of 40.5%-kcal fat. Group 2 received the 40.5%-kcal fat diet plus
      supplemental Vitamin E. Group 3 received a diet of 21.2%-kcal fat. Group 4
      received the 21.2%-kcal fat diet plus supplemental Vitamin E. Food intake, animal
      weights, and tumor volumes were recorded weekly. Survival analyses with time to a
      target volume of 0.523 cm.3 (defined as failure) were used to compare tumor
      growth among the 4 groups. Two-sided tests (log rank test) with alpha set at 0.05
      were used to determine significance. RESULTS: Tumor growth rates were highest in
      the animals fed a 40.5%-kcal fat diet (p <0.05 group 1). Tumors in animals fed
      40.5%-kcal fat plus Vitamin E, 21.2%-kcal fat, and 21.2%-kcal fat plus Vitamin E,
      experienced statistically indistinguishable growth rates. No significant
      differences were noted in total ingested calories, animal weight gain or initial
      PSA levels. CONCLUSIONS: These data suggest that the mechanism of dietary fat
      induced growth of human prostate cancer cells is mediated by oxidative stress. It
      also raises the possibility of a therapeutic benefit of vitamin E in preventing
      prostate cancer.

PMID- 10210434
TI  - Hoxa-13 gene mutation results in abnormal seminal vesicle and prostate
      development.
AB  - The role of Hoxa-13 in postnatal morphogenesis of the male accessory sex organs
      was assessed by correlating the Hoxa-13 expression domain with phenotypic
      abnormalities in heterozygous Hypodactyly mutants. Hypodactyly is a naturally
      occurring semi-dominant mutation that results from a 50-base pair deletion in
      exon one of the Hoxa-13 allele. We demonstrate that Hoxa-13 is broadly expressed
      in the developing lower genitourinary tract and that the Hypodactyly mutation
      results in a specific phenotype characterized by decreased size and branching of
      the dorsolateral and ventral prostate and abnormal seminal vesicle morphology.
      This phenotype partially overlaps the genitourinary phenotype observed in Hoxd-13
      deficient mice and comparison showed similar domains of Hoxa-13 and Hoxd-13
      expression in the lower genitourinary tract. The similarity in expression and
      overlap in phenotype resulting from mutation is consistent with additive function
      and partial functional redundancy of Hoxa-13 and Hoxd-13 in male accessory sex
      organ development.

PMID- 10210435
TI  - Bladder welding in rats using controlled temperature CO2 laser system.
AB  - PURPOSE: Laser tissue welding has potential advantages over conventional suture
      closure of surgical wounds. It is a noncontact technique that introduces no
      foreign body and limits the possibility of infections and complications. The
      closure could be immediately watertight and the procedure may be less traumatic,
      faster and easier. In spite of these positives laser welding has not yet been
      approved for wide use. The problem in the clinical implementation of this
      technique arises from the difficulty in defining the conditions under which a
      highly reliable weld is formed. We have assumed that the successful welding of
      tissues depends on the ability to monitor and control the surface temperature
      during the procedure, thereby avoiding underheating or overheating. The purpose
      of this work was to develop a laser system for reliable welding of urinary tract
      tissues under good temperature control. MATERIALS AND METHODS: We have developed
      a "smart" laser system that is capable of a dual role: transmitting CO2 laser
      power for tissue heating, and noncontact (radiometric) temperature monitoring and
      control. Bladder opening (cystotomy) was performed in 38 rats. Thirty-three
      animals underwent laser welding. In 5 rats (control group) the bladder wound was
      closed with one layer of continuous 6-0 dexon sutures. Reliable welding was
      obtained when the surface temperature was kept at 71 + 5C. Quality of weld was
      controlled immediately after operation. The rats were sacrificed on days 2, 10
      and 30 for histological study. RESULTS: Bladder closure using the laser welding
      system was successful in 31/33 (94%) animals. Histological examination revealed
      an excellent welding and healing of the tissue. CONCLUSIONS: Efficiency of laser
      welding of urinary bladder in rats was confirmed by high survival rate and
      quality of scar that was demonstrated by clinical and histological examinations.
      In the future, optimal laser welding conditions will be studied in larger
      animals, using CO2 lasers and other lasers, with deeper radiation penetration
      into tissues.

PMID- 10210436
TI  - Synaptic responses evoked by lower urinary tract stimulation in superior cervical
      ganglion cells in the rat.
AB  - PURPOSE: Stimulation of afferent neurons from the urinary tract can evoke
      powerful cardiovascular reflexes in animals and in humans. Here we tested whether
      and to what extent postganglionic sympathetic neurons projecting to the head and
      neck are involved in these reflexes. MATERIALS AND METHODS: In adult anesthetized
      female Wistar rats, reflex changes in synaptic activity elicited from the lower
      urinary tract were recorded in neurons of the superior cervical ganglion using
      intracellular recording techniques. RESULTS: Gentle movements of the urethral
      cannula and/or slow injections of 0.3 to 0.6 ml. saline into the bladder modified
      synaptic activity in 75% of neurons tested: 11/15 neurons tested showed reflexes
      to urethral stimulation (8 excitatory, 3 inhibitory) and 8/12 neurons responded
      to bladder distension (5 excitatory, 3 inhibitory). Five neurons showed a
      reciprocal response pattern to the two stimuli. Suprathreshold and subthreshold
      inputs to a given cell mostly showed the same type of response. There was no
      evidence that urinary tract stimulation recruited preganglionic inputs that did
      not have ongoing activity prior to the stimulus. CONCLUSIONS: Reflexes from the
      lower urinary tract clearly reached sympathetic neurons located in remote
      segments. The response incidence in the population studied suggests that most
      sympathetic neurons involved in cardiovascular regulation participate in these
      reflexes. The different reflex patterns probably occur in neurons with different
      functional targets in the head and neck.

PMID- 10210437
TI  - Genotypes of N-acetyltransferase-2 and risk of bladder cancer: a case-control
      study.
AB  - PURPOSE: This study was conducted to examine whether certain slow N-acetylation
      genotypes could be risk factors for bladder cancer, and the possible association
      between specific genotypes and the severity of the disease at first diagnosis.
      MATERIALS AND METHODS: This case-control study included 89 patients with
      transitional cell bladder cancer (diagnosed over a period of 21 months) and 147
      controls. N-acetyltransferase-2 (NAT-2) genotypes were identified by allele
      specific polymerase chain reaction (PCR) on peripheral blood DNA samples. The x2
      test was used for statistical evaluation to compare the differences observed
      between patients and controls and the different genotypes with tumor grading and
      local staging at presentation. Relative, attributable and population attributable
      risks were estimated for the genotypes found to present a significantly increased
      frequency for bladder cancer. RESULTS: A statistically significant difference in
      the frequency of genotypes was found between the two groups. The patient group
      had the higher frequency of slow acetylation genotypes (p = 0.0016). Among slow
      acetylators, homozygotes 341C/341C and compound heterozygotes 341C/857A had the
      most excessive risk for bladder cancer (p = 0.0041 and 0.0031, respectively). The
      341C/341C genotype was found to be associated with more aggressive disease, in
      terms of tumor grading at presentation (p <0.05). CONCLUSIONS: According to our
      data, slow acetylators with 341C/341C and 341C/857A genotypes carry a
      substantially higher odds ratio (3.73 and 12.46, respectively) for bladder
      carcinogenesis. Additionally, among the slow acetylators, 341C/341C homozygotes
      are likely to have a higher risk for more aggressive disease.

PMID- 10210438
TI  - Migration and ultrastructural localization of the c-kit receptor protein in
      spermatogenic cells and spermatozoa of the mouse.
AB  - PURPOSE: The c-kit receptor is a proto-oncogene important in germ cell migration
      and maturation and has also been demonstrated on the acrosomal region of mature
      sperm. The purpose of the present study was to examine the ultrastructural
      location of the c-kit receptor in mouse testis and sperm. MATERIALS AND METHODS:
      Testis and sperm from mature male mice were examined for the c-kit receptor
      utilizing electron microscopy and Western blot analysis techniques. Thin sections
      of mouse testis and sperm were stained with immunogold-labeled anti-c-kit
      antibodies. The protein from these testes and sperm was also utilized for Western
      blot analysis. RESULTS: The c-kit protein was localized within the mouse testes
      to the type A spermatogonia, the round spermatids, and the mature testicular
      spermatozoa. The c-kit receptor was noted to migrate from the lumen of the
      acrosomal vesicles in the early spermatids to the plasma membrane of the late
      spermatids. It was also noted in the acrosomal region of the testicular
      spermatozoa, as well as the sperm from the epididymis. Sperm undergoing the
      acrosome reaction demonstrated association of the c-kit receptor with the plasma
      membrane of the acrosome, but not on the acrosomal membrane itself. Western blot
      analysis demonstrated protein bands of 150 kDa in testis and intact sperm.
      CONCLUSIONS: The present study confirms the presence of the c-kit receptor in
      mouse testis and sperm. It also demonstrates that this receptor is localized to
      the region of the developing acrosome.

PMID- 10210439
TI  - Suppression of renal inflammation with vitamins A and E in ascending
      pyelonephritis in rats.
AB  - PURPOSE: We evaluated the effects of vitamin A and E supplementation alone or in
      combination with non-steroidal anti-inflammatory drugs (NSAIDs) on the
      development of inflammation in an animal model of ascending pyelonephritis.
      MATERIALS AND METHODS: Ascending pyelonephritis was induced in adult rats by
      surgical bladder inoculation with P-pili-forming Escherichia coli. Treatment of
      pyelonephritic rats was initiated at 72 hours post-infection. Treatment groups
      included no treatment, or a five day regimen of antibiotic only, antibiotic plus
      vitamins A and E, or antibiotic, vitamins and either of two NSAIDs. Kidneys were
      harvested at six weeks post-infection and assessed for histopathologic
      inflammation. RESULTS: Antibiotic treatment of pyelonephritic rats with vitamins
      A and E alone or in combination with NSAIDs resulted in significantly less kidney
      inflammation, as compared with untreated rats or rats treated with antibiotic
      alone. There was no significant difference in inflammation between animals
      treated with vitamins alone or vitamins plus NSAIDs. CONCLUSIONS: Antibiotic
      therapy and diet supplementation with vitamins A and E can significantly reduce
      the inflammation associated with ascending pyelonephritis, suggesting a potential
      use in the medical management of reflux nephropathy in children.

PMID- 10210440
TI  - Examination of crystalluria in freshly voided urines of recurrent calcium stone
      formers and normal individuals using a new filter technique.
AB  - PURPOSE: We evaluated calcium oxalate (CaOx) and calcium phosphate (CaP)
      crystalluria in freshly voided urines of normal individuals (controls) and
      recurrent calcium stone formers (RSF) using a new filter technique. MATERIALS AND
      METHODS: Chemical analysis of urinary sediment retained by a 0.45 microm.
      Millipore filter was used to quantitate crystalluria. A CaOx and CaP crystal
      suspension initially confirmed the reliability of the filter technique. Freshly
      voided urine samples from 11 controls and 15 RSF were then evaluated. Sediment
      calcium (S-Ca), oxalate (S-Ox) and phosphate (S-PO4) were compared with routine
      light microscopy for crystal detection. RESULTS: The recoveries of calcium (Ca)
      and oxalate (Ox) from the CaOx crystal suspension were 83.8% and 87.5%,
      respectively. The recoveries of Ca and phosphate (PO4) from the CaP crystal
      suspension were 97.7% and 89.7%, respectively. The CaOx and CaP crystal volumes
      (S-Ox and S-PO4) were similar between controls and RSF. However, the sediment to
      urinary ionic ratios, a parameter indicative of crystal formation under similar
      levels of supersaturation, was significantly higher in RSF. S-PO4 was 3 to 4
      times higher than S-Ox, both in controls and RSF. There was a strong positive
      correlation between urinary Ox (U-Ox) concentration, and S-Ox and S-Ca
      concentrations in RSF, but not in controls. There was also a positive correlation
      between urinary phosphate (U-PO4) and S-PO4 in both groups. A good correlation
      was also found between the filter technique and standard microscopy for the
      detection of crystalluria. CONCLUSIONS: We conclude that the filter technique is
      a simple and sensitive quantitative method to study crystalluria. The predominant
      crystal type in fresh urines of both controls and RSF appears to be calcium
      phosphate. The principal difference between crystalluria of RSF and normals is
      its tendency to form at a lower urinary ionic concentration in RSF, suggesting a
      higher crystallization inhibitor activity in normal individuals.

PMID- 10210441
TI  - Persistently increased voiding frequency despite relief of bladder outlet
      obstruction.
AB  - PURPOSE: Bladder outlet obstruction (BOO) can increase urinary frequency. Even
      after surgical relief of obstruction, up to 30% of patient are still bothered by
      irritative voiding symptoms. We tested the hypothesis that deligation of a
      partial bladder outlet obstruction model mimics this clinical observation.
      MATERIALS AND METHODS: Female Wistar rats were obstructed for 3 weeks by partial
      urethral ligation and then were relieved of obstruction by urethral deligation.
      Measurements of voiding frequency and voided volumes were measured
      preoperatively, after ligation, and after deligation. Relief of obstruction was
      confirmed by measuring flow rates through ex vivo perfusion of deligated
      urethras. Urine osmolality and bladder weights were determined. Awake
      cystometrograms (CMGs) were performed 3 weeks after deligation to measure bladder
      function. RESULTS: Neither sham ligation nor sham deligation altered voiding
      frequency. Ligation doubled mean voiding frequency (in cc) from 2.01 +/- 0.32 to
      3.96 +/- 0.22 per 4 hours (p = 0.0002). Three weeks after deligation, voiding
      behavior of the animals segregated into 2 groups: 20% had persistent hyperactive
      voiding frequency (6.67 +/- 1.23 per 4 hours) while 80% normalized voiding
      frequency (1.53 +/- 0.20 per 4 hours). The difference in voiding frequency in
      these 2 groups could not be attributed to alterations in urine osmolality,
      persistence of urethral obstruction, difference in bladder weights or severity of
      initial obstruction created. Awake CMGs revealed a higher peak micturition
      pressure and lower voided volume in the hyperactive voiders. CONCLUSIONS: 20% of
      the animals after urethral deligation had persistent hyperactive voiding which
      parallels clinical observations. Because the CMG data suggested persistent
      obstruction, yet urethral perfusion and bladder weights indicated no obstruction,
      we propose that these 20% of animals have a "functional" bladder outlet
      obstruction and can be used to study mechanisms underlying hyperactive voiding.

PMID- 10210442
TI  - Prostate gland growth during development is stimulated in both male and female
      rat fetuses by intrauterine proximity to female fetuses.
AB  - In rodents, steroid hormones are transported between adjacent fetuses, and male
      or female fetuses that develop in utero between female fetuses (2F males or 2F
      females) have higher serum levels of estradiol and lower serum levels of
      testosterone relative to siblings of the same sex that develop between two male
      fetuses (2M males or 2M females). The present study was prompted by the prior
      unexpected finding that as adults, 2F male mice have an enlarged prostate, and
      increased numbers of prostatic androgen receptors relative to 2M males. We
      examined prostate development in both male and female rat fetuses from different
      intrauterine positions using computer-assisted, 3-dimensional reconstruction of
      the urogenital complex. In males, this included the prostate, seminal vesicles
      and utricle (a remnant of the Mullerian ducts), while in females it included
      development of prostatic glandular buds. The mean cross-sectional area of
      developing prostatic epithelial buds, utricle and seminal vesicles was
      significantly increased in 2F male relative to 2M male fetuses. In female
      fetuses, prostatic bud development was significantly more likely to occur in 2F
      (67%) than in 2M (29%) animals. These findings suggest that the transport of a
      small supplement of estrogen from adjacent female fetuses enhances androgen
      dependent accessory organ development. We also found that mRNAs encoding
      receptors for both estrogen and androgen were located in the mesenchyme of the
      developing male prostate. The localization of estrogen and androgen receptor mRNA
      in this region further suggests that the mesenchymal induction of prostatic
      epithelial growth involves both hormones. The cranial dorsolateral prostatic buds
      exhibited the greatest enlargement in 2F males. This region of the developing
      prostate in rats is comparable (that is the embryonic homologue) to the region
      exhibiting benign prostatic hyperplasia (BPH) during aging in men. We propose
      that the potential for pathological regrowth of the prostate during aging is
      imprinted by estradiol during fetal development.

PMID- 10210443
TI  - Effects of acetylic salicylic acid and pentoxifylline on the efficacy of
      intravesical BCG therapy in orthotopic murine bladder cancer (MB49).
AB  - PURPOSE: Intravesical immunotherapy with bacillus Calmette-Guerin (BCG), which
      has become the gold standard in the adjuvant treatment of superficial bladder
      cancer, is hampered by local side effects. Anti-inflammatory drugs may be
      helpful, but as an undesired side effect, therapeutic efficacy of BCG might be
      impaired. Therefore, we investigated the effects of anti-inflammatory drugs on
      the efficacy of intravesical BCG in an animal model. MATERIALS AND METHODS:
      Syngenic tumor cells were implanted into the bladders of 75 mice according to our
      modification of the method. Mice were randomized to 5 groups with 15 animals each
      and treated with phosphate buffered saline (PBS), group 1; BCG, group 2; BCG +
      acetylic salicylic acid (ASA), group 3; BCG + pentoxifylline (POF), group 4;
      autoclaved BCG (aBCG), group 5. Intravesical instillation of 1.35 mg. BCG was
      initiated one day after tumor inoculation and repeated in weekly intervals for 4
      instillations altogether. ASA and POF in doses of 200 mg./kg. and 150 mg./kg.,
      respectively, were given continuously with the drinking water starting at the
      first instillation. Autoclaved BCG served as control for the importance of
      viability and was given at the same dose as viable BCG. Mice were monitored for
      survival, gross hematuria and body weight and after 28 days evaluated for bladder
      weight and tumor occurrence. RESULTS: Autoclaved BCG and PBS had no effect on
      tumor growth, whereas animals treated with viable BCG alone and in combination
      with POF and ASA, respectively, showed a significant reduction in bladder weight:
      PBS, 248 mg.; BCG, 140 mg. (p = 0.0009); BCG + ASA, 123 mg. (p = 0.0001); BCG +
      POF, 145 mg. (p = 0.0004); autoclaved BCG, 283 mg. (p = 0.21). Mice treated with
      BCG, BCG + ASA and BCG + POF showed a significantly higher proportion of survival
      until day 28 as compared to PBS alone. Autoclaved BCG had no therapeutic efficacy
      (Kaplan-Meier method/log rank test: BCG, p = 0.0053; BCG + ASA, p = 0.0044; BCG +
      POF, p = 0.0027; aBCG, p = 0.33). No significant differences among the 3 groups
      treated with viable BCG, with or without anti-inflammatory drugs, regarding
      bladder weight and survival were detectable. CONCLUSIONS: The efficacy of BCG
      therapy in murine orthotopic bladder cancer is dependent on BCG viability and is
      not compromised by ASA or POF. Clinical trials to evaluate the efficacy of
      routine ASA or POF to reduce BCG side effects in patients, using self-assessment
      criteria, should be initiated.

PMID- 10210445
TI  - Penile prosthetic infection: management by delayed and immediate salvage
      techniques.

PMID- 10210446
TI  - Bethina A. Bennett and the University of Leeds Diploma in Nursing.

PMID- 10210444
TI  - The effect of sildenafil on apomorphine-evoked increases in intracavernous
      pressure in the awake rat.
AB  - PURPOSE: The aim of this study was to develop a quantitative, awake animal model
      to investigate the effect of sildenafil on centrally-evoked erectile activity.
      METHODS: Intracavernous pressures were recorded in awake, male Sprague Dawley
      rats after administration of apomorphine (100 or 250 microg./kg. subcutaneously).
      Sildenafil (100 microg./kg. intravenously) was then given 10 min. after a second
      dose of apomorphine. The time to first response, duration of response, and peak
      intracavernous pressure and area under the response, were measured before and
      after sildenafil. RESULTS: Apomorphine produced rhythmic increases in
      intracavernous pressure. The pressure increase consisted of two components. The
      amplitude of the first, tonic response was 58 +/- 3 mm. Hg, and a superimposed,
      burst-like increase in pressure elevated this further to 81 +/- 6 mm. Hg.
      Bilateral transection of the pudendal nerves abolished the burstlike pressure
      changes; bilateral transection of the cavernous nerves prevented both responses.
      The duration of the apomorphine-induced increase in intracavernous pressure was
      significantly (p = 0.003) prolonged by sildenafil (100 microg./kg.) from 37 +/- 4
      to 62 +/- 11 s (n = 6). The overall intracavernous pressure response to
      apomorphine (100 microg./kg.), measured as the area under the curve, was
      significantly (p = 0.003) increased by sildenafil (100 microg./kg.) from 67 +/- 8
      to 142 +/- 31 units (n = 6). N-nitro-L-arginine methyl ester (40 mg./kg.
      intravenously) prevented the apomorphine-induced responses. CONCLUSIONS:
      Monitoring intracavernous pressures in the awake rat represents a simple model to
      evaluate the effect of drugs on erectile function. Using this model we have shown
      that apomorphine elicits a rise in intracavernous pressure that can be prolonged
      by sildenafil. These results suggest that there may be a role for the combination
      of apomorphine and sildenafil in the management of erectile dysfunction.

PMID- 10210447
TI  - Aggression in clinical settings: nurses' views--a follow-up study.
AB  - Results from this empirical study (n = 270) indicate that nurses from both the
      public and private sector are more worried about colleague aggression than
      aggression from other sources, that such aggression ranks as a major workplace
      distress factor for them, that different clinical settings have their own
      profiles of aggression, and following incidents of aggression, staff talk with
      colleagues and friends rather than with human resource or trade union personnel.
      These findings shadow those of a previous small scale qualitative study conducted
      by the author and they add to the growing recognition and concern that nurses,
      like employees in other settings, are subjected to high levels of interpersonal
      conflict at work.

PMID- 10210448
TI  - Socio-cultural perspectives on the image of nursing: the Hong Kong dimension.
AB  - Using structured interviews a study was undertaken with 19 high school students
      in Hong Kong to elicit their perceptions of nursing as a profession. The study
      also sought to gauge the extent of the students' intentions on pursuing a career
      in nursing. Responses were content analysed to determine the extent of knowledge
      and understanding held, intentions on choosing nursing as a career and their
      reasons. Findings suggest the image of nursing to be poor and that nursing as a
      career is far from desirable amongst the teenagers of Hong Kong. The reasons
      appear to be related to the notion of monetary rewards and status within the Hong
      Kong community. There is also a lack of knowledge as to what nurses do. The
      implications of such findings include the lost potential for recruitment of
      candidates of high calibre with a lot to offer the profession and their society.
      It suggests the need for the profession to find ways of publicizing and marketing
      the positive aspects with elements of realism which the general population in
      that part of the world could relate to more readily.

PMID- 10210449
TI  - How can we achieve evidence-based practice if we have a theory-practice gap in
      nursing today?
AB  - The purpose of this paper is to discuss how nursing can achieve evidence-based
      practice when a theory-practice gap exists in nursing today. The paper commences
      with an introduction to the concept of evidence-based practice and a discussion
      of the relationships between theory, practice and the theory-practice gap. An
      analysis of the two concepts will then be presented from within the four pillars
      of nursing, namely management, practice, research and education. The paper will
      conclude with a discussion of whether evidence-based practice can be achieved in
      view of the theory-practice gap.

PMID- 10210450
TI  - A concept analysis of autonomy.
AB  - Clinical and policy developments in health care have recently created demand for
      a professional response in terms of the development of advanced roles for nurses,
      notably 'nurse practitioner' roles. Such roles demand the exercise of autonomy, a
      term which eludes succinct definition despite the fact that the preparation of
      practitioners for these roles relies on a clear understanding of its nature.
      Utilizing an approach described by Wilson, this paper undertakes a concept
      analysis of autonomy, each step illustrated with examples taken from clinical
      practice, with the ultimate aim of offering an operational definition of
      autonomy.

PMID- 10210451
TI  - The idea of nursing science.
AB  - This paper addresses the question of whether or not nursing can legitimately be
      considered as a science. It is proposed that an adequate answer to this question
      requires consideration of recent developments in philosophy of science (as urged
      by Paley). It is shown that such developments call into question the 'rational
      image' of science. However, a defence of the legitimacy of the scientific
      enterprise has been attempted by Laudan, an advocate of the 'historical turn'.
      Two conditions necessary for the applicability of this 'turn' are identified. It
      is shown that although they apply relatively unproblematically to science, they
      do not readily apply to nursing. Hence the conclusion is drawn that claims for
      the integrity of nursing science stand in need of much further development.

PMID- 10210452
TI  - Parental autonomy and consent to treatment.
AB  - This paper discusses the principle of autonomy in relation to minors and
      considers the complexities of parental responsibility regarding consent to
      treatment. The author considers the case of a child with leukaemia and draws on
      her own experiences as a parent to highlight the ethical dilemmas for health care
      professionals who may be in a position to support parents in consenting to
      treatment on behalf of their child.

PMID- 10210453
TI  - Catching the wave: understanding the concept of critical thinking.
AB  - As a practice-orientated profession, nursing is clearly guided by theoretical
      concepts. Concept clarification attempts to show speakers and readers how they
      can liberate themselves from the judgement limitations imposed by rigid,
      unexamined beliefs, by exposing differences in the interpretation of language and
      how that interpretation creates meaning. Critical thinking is one way nurses
      apply the process of inquiry. As a method of assessing, planning, implementing,
      evaluating and reconstructing nursing care, a critical thinking approach
      encourages nurses to challenge established theory and practice. Existing
      literature on critical thinking is confusing in its description of the process,
      and ambiguous in drawing relationships between critical thinking and the language
      currently used to illustrate the process of nursing. This paper examines elements
      and components of critical thinking as they relate to the language of nursing:
      problem solving, decision making, clinical judgement, reflection, and the nursing
      process. The purpose of this analysis is to illuminate the meaning and clarify
      the intent of critical thinking application to nursing practice. The paper begins
      by briefly outlining the historical aspects of critical social theory, suggesting
      that the foundational tenets of critical theory have influenced the development
      of critical thinking. The paper also critically compares the language used to
      describe critical thinking and that language that has traditionally defined
      nursing.

PMID- 10210454
TI  - Primary nursing: a mode of care or a philosophy of nursing?
AB  - An examination of the literature surrounding primary nursing has shown that the
      term 'primary nursing' is used to mean different things by different authors.
      This results in a confusing situation where 'primary nursing' is considered by
      some to mean both a mode of organizing care delivery and a philosophy of nursing.
      In this paper I argue for a clear separation between the terms which refer to the
      set of ideas underpinning nursing and descriptions of modes of care. A case is
      made for using the term 'human centred nursing' to refer to nursing beliefs and
      'primary nursing' to refer to the mode of nursing care delivery.

PMID- 10210455
TI  - Facing the issue of dependence: some implications from the literature for the
      hospice and hospice nurses.
AB  - Research and clinical practice suggest that dependence upon others causes
      distress to those with a life-threatening illness and that the hospice may serve
      to reinforce feelings of loss of autonomy. Hospice nurses can contribute to good
      care and act therapeutically to maximize an individual's potential for
      independent activity where this is possible and desirable. However, literature
      from other contexts demonstrates variability in the extent to which this is
      achieved. This paper outlines the problem of dependence in those with a life
      threatening illness. Therapeutic nursing is explored in relation to issues which
      may arise in a hospice context, potential relationships between therapeutic
      nursing and partnership are noted, particularly with regard to the possible
      meanings of dependence which for some individuals comes to be apprehensively
      associated with impending death.

PMID- 10210456
TI  - A concept analysis of empowerment: its relationship to mental health nursing.
AB  - The concept of empowerment is described as being intuitively attractive to nurses
      and the nursing profession. This concept analysis represents an attempt not only
      to clarify meaning but also to describe the relationship, if any, between
      empowerment and mental health nursing. It is the argument of this author that the
      conceptual ambiguity said to blight the implementation of empowerment practice is
      underpinned by a tendency to describe the concept without direct reference to
      theories of power. As regards mental health nursing the author concludes that
      there should be an end to the quest for professionalism personified by notions
      such as individualized care. In its place should be an approach that recognizes
      that nurses and users must unite to pursue forms of knowledge that precipitate a
      challenge to the current hegemony of the medical and scientific elite.

PMID- 10210457
TI  - Assisting demented patients with feeding: problems in a ward environment. A
      review of the literature.
AB  - A critical review of the literature on assisting demented patients with feeding
      difficulties identifies that care at mealtimes is often task-centred, causing
      stress in both patients and staff and inadequate patient care. Nurses may even be
      inducing dependency in this vulnerable patient group. The staff to whom this care
      is most often delegated do not receive sufficient education or training to enable
      them to achieve a sufficient degree of empathy with the patient although there is
      evidence in the literature to suggest that this is a necessary requirement. It is
      also apparent that nurses use inadequate assessment criteria, perhaps due to the
      fact that there is an element of commonality in the feeding behaviour of demented
      patients which nurses feel they have seen many times and are able to deal with.
      The introduction of primary nursing, increased education of nursing assistants
      and improved assessment procedures to combat these problems are recommended. The
      process of change is briefly outlined and in conclusion some areas for future
      research are stated.

PMID- 10210458
TI  - Atypical neuroleptics: autonomy and compliance?
AB  - Non-compliance is a major stumbling block to the effectiveness of drug therapy.
      The nurse, both in hospital and community, has a crucial role to play in
      overcoming this problem to the benefit of the patient. Recent treatment advances,
      'new-generation' anti-depressants and atypical neuroleptics, make this issue
      highly topical in mental health nursing. The atypical neuroleptics are a
      pharmacological breakthrough in the treatment of schizophrenia, which could
      herald a new era in psychiatry. These medicines give the benefits of the older
      (typical) neuroleptics but with fewer side-effects. Neuroleptics are sometimes
      called antipsychotics, antischizophrenics or major tranquillisers. Currently the
      atypical neuroleptics are not available in depot form. This critical review
      considers literature on interventions to promote compliance with neuroleptics
      generally and reflects on nursing implications relevant to the atypical
      neuroleptics. Three main forms of interventions emerge from the review; these are
      labelled as: imposed compliance, chosen compliance and active compliance.
      Historically the literature shows a gradual trend towards a realization by
      professionals that increased patient autonomy and involvement relates to improved
      compliance. This change in thinking is reflected in the new name 'adherence',
      which has begun to replace the term 'compliance'. It is concluded that mental
      health nurses have a key role to play in enabling this reconceptualization to
      change practice.

PMID- 10210459
TI  - Maternal depression and child behaviour problems: a meta-analysis.
AB  - Children of depressed mothers are not only at risk for the development of
      psychopathology, but also for behaviour problems. A meta-analysis of 33 studies
      was conducted to determine the magnitude of the relationship between maternal
      depression and behaviour problems in children 1 year of age and older.
      Substantive, methodological, and miscellaneous variables were extracted and coded
      by both the researcher and a research assistant. The initial inter-rater
      agreement reached in coding these variables ranged from 85% to 100%. Effect sizes
      were calculated in three ways: unweighted, weighted by sample size, and weighted
      by quality index score. The mean effect size for the r index ranged from 0.29
      when weighted by sample size to 0.35 when unweighted, indicating a moderate
      relationship between maternal depression and child behaviour problems. Children
      between the ages of 1-18 whose mothers were depressed displayed more conduct
      behaviour problems than children whose mothers were not depressed. The magnitude
      of this relationship covaried significantly with the predictors of sample size
      and quality index scores. Implications for future research are addressed.

PMID- 10210460
TI  - From novice to competent practitioner: tracking the progress of undergraduate
      mental health nursing students.
AB  - This study explores the perceptions of, and outcomes for, a group of
      undergraduate mental health nursing students over a 3-year period from the point
      at which they made their choice to take the mental health branch of a 4-year
      degree programme in nursing, to working in the practice setting as registered
      nurses. Semi-structured interviews were completed at three points in their
      career: (a) at the end of the common foundation programme, when students had made
      their choice to take the mental health option; (b) at the end of the fourth year
      of the undergraduate programme; and (c) 1 year post-qualification. Questions were
      generated around five main themes: career choice, personal change and
      development, evaluation of the curriculum, ideas about mental health nursing and
      career plans. Despite some initial ambivalence at the start of the branch,
      students were happy with their career choice at follow-up, which was reinforced
      by significant clinical progress. All of the group were working in acute hospital
      settings despite being in possession of the community mental health
      qualification. Substantial evidence of these students' 'fitness for purpose' is
      offered, although some disillusionment with the contrast between student life and
      the real world of work is noted. Questions are posed as to the role of clinical
      supervision and education in preventing negative professional socialization.
      Recommendations are also made about recruitment to and design of mental health
      nursing courses.

PMID- 10210461
TI  - The professional socialization of diploma of higher education in nursing students
      (Project 2000): a longitudinal qualitative study.
AB  - This paper presents a new theory of professional socialization in relation to
      diploma of higher education in nursing students (Project 2000). It was derived
      from a 3-year, grounded theory, longitudinal study exploring the effects of
      supernumerary status and mentorship on students undertaking practice placements.
      A purposive sample of 17 students was used. Ten students volunteered to be
      interviewed on five separate occasions throughout their course and to keep a
      diary to record their experiences of mentorship during their practice placements.
      Their diary acted as an aide memoir during their tape-recorded interviews. The
      other seven students participated by diary only and kept written accounts of
      their experiences of being supernumerary and having a mentor whilst on practice
      placements. Data were analysed with the aid of NUD.IST and subjected to the
      constant comparative method of analysis. Findings indicate that the mentor is the
      linchpin of the students' experience and that some students develop intuition
      much earlier than previous work has stated.

PMID- 10210462
TI  - Conceptualizing disability in nursing: some evidence from students and their
      teachers.
AB  - This paper reports on part of a larger study which examined the nature and
      influence of a pre-registration nursing curriculum on the preparation of student
      nurses to work with disabled people. Following case study methodology it focuses
      on how 'disability' is conceptualized by teachers and adult branch students
      involved in a particular curriculum. Definitions and working assumptions
      concerning disability held by nurses are likely to influence ways in which
      disabled people are cared for. The experiences of disabled people suggest that
      their contact with nurses is demeaning and disempowering. Some disabled people
      support a reconceptualization of 'disability', from a largely medical perspective
      to one which embraces its social dimensions. The results of thematic analysis of
      data from 16 semi-structured interviews are reported; these support the need for
      the social dimensions of disability to be given greater emphasis within nursing.
      Disability was found to be conceptualized as a form of deviation, a condition of
      dependency or a notion which defies definition. Language associated with
      disability was also highlighted as an area of concern. Implications for practice
      and education are alluded to in the light of increasing recognition of disability
      as an equality opportunity issue.

PMID- 10210463
TI  - Assessing nursing students' basic communication and interviewing skills: the
      development and testing of a rating scale.
AB  - This study explores the communication skills of a group of nursing students who
      were required to interview a simulated client as part of their studies. In order
      to assess the students and to improve the process of learning discrete skills, an
      instrument was developed and tested as part of this process. The subjects were
      212 nurses enrolled in a bachelor of nursing programme, in New South Wales,
      Australia, who were studying a problem-based learning package the focus of which
      was 'alcohol early intervention'. The sub-groups within the sample included
      registered nurses, a significant percentage of whom had completed their basic
      nursing education in overseas countries. The Simulated Client Interview Rating
      Scale (SCIRS) was developed to assess basic humanistic communication skills as
      well as beginning motivational interviewing skills. The students were required to
      interview a simulated client and demonstrate competence in interviewing. This was
      assessed by the SCIRS which was completed by the students and the simulated
      clients. The instrument proved to be a reliable and valid means of assessing
      student interview technique as well as a flexible educational tool, while
      valuable insights into students' interviewing techniques were gained.

PMID- 10210464
TI  - A task-based approach to defining the role of the nurse practitioner: the views
      of UK acute and primary sector nurses.
AB  - There exists within the United Kingdom considerable confusion relating to the
      definition and occupational boundaries of the nurse practitioner (NP). In
      consequence, the clinical practice and training of the NP remain unregulated,
      unstandardized and heavily dependent on local forces. Such a situation is
      regrettable, particularly in view of the potential value the nurse practitioner
      has for health care provision and also for influencing national policy decisions.
      It is conceivable that one reason for the current failure to reach agreement over
      the role definition of the nurse practitioner relates to the fact that their
      essential job functions depend upon the context in which the nurse practitioner
      operates, with primary-based practice differing from acute sector service
      delivery in sufficient critical ways as to make a generic, inclusive definition
      impossible. To investigate the veracity of this view, two cohorts of United
      Kingdom nurses were sampled, one of which worked within the acute sector (n = 49)
      and the other in the community (n = 420). These groups were surveyed using a
      unique training needs analysis instrument that had been developed along formal
      psychometric principles. Both groups perceived advanced clinical activities,
      including examination and diagnosis, and a range of research activities to be
      central to the role of the nurse practitioner. The primary sample, however,
      reported business and management activities as essential tasks, while the acute
      sector nurses regarded high levels of communication skills, autonomy and risk
      management to be more important. The implications of the similarities and
      differences between the two data sets are discussed with reference to different
      clinical domains.

PMID- 10210465
TI  - Clinical Development Units (Nursing): the western Sydney approach.
AB  - On 24 September 1997 Western Sydney Area Health Service and the University of
      Western Sydney, Nepean (Australia) launched a network of nine Clinical
      Development Units (Nursing). The approach taken towards the development of
      CDU(N)s in western Sydney differs substantially from those taken elsewhere in
      terms of preparation for CDU(N) leadership and the role of CDU(N) criteria in the
      designation ('accreditation') process. The rationale underpinning the western
      Sydney approach, together with details of a leadership preparation programme, are
      discussed.

PMID- 10210466
TI  - Evaluating the impact of primary nursing practice on the quality of nursing care:
      a Nigerian study.
AB  - This paper is abstracted from an action research project on promoting family
      centred care in Nigeria through the practice of Nigerian Primary Nursing (NMPN).
      This article will present results of comparative evaluation of the impact of
      primary nursing on the quality of care received by patients in a 37-bedded acute
      medical-surgical, mixed sex ward in a specialist hospital in eastern Nigeria. A
      total of 44 nurses' interactions with 10 patients in the pre-NMPN period and 58
      nurses' interactions with eight patients in the post-NMPN period were assessed
      using QUALPACS (Quality Patient Care Scale.). Results showed a significant
      improvement in the quality of nursing care with primary nursing practice. The
      greatest improvement in quality of nursing appeared to be in the elements that
      address the individual needs of the patient, while the smallest improvements were
      in the area of physical care--elements of routine, technical nursing care.
      Implications of the study and recommendations for further studies are made.

PMID- 10210467
TI  - Post-operative pain, nausea and vomiting: qualitative perspectives from telephone
      interviews.
AB  - Previous studies on post-operative pain, nausea and vomiting tend to be
      quantitative in method and focus on in-patient or day case surgery. The
      objectives of this study carried out in one specialist eye hospital in England
      were to consider post-operative pain, nausea and vomiting from a qualitative
      perspective. Fifty-five patients undergoing general anaesthetic short-stay
      ophthalmic surgery (orbital hydroxyapatite implantation) consented to participate
      in telephone interviews 8 days post-surgery. The interviews lasted between 20 and
      60 minutes. Data were analysed thematically and offer insight into varying
      experiences of pain, nausea and vomiting in hospital, on discharge and at home.
      Results indicate that not all patients were discharged home in optimum condition.
      The needs of post-operative short-stay patients should come before financial
      imperatives to vacate beds. Patient education and information giving is discussed
      in the light of the findings.

PMID- 10210468
TI  - Meaning in caring: reconceptualizing the nurse-family carer relationship in
      community practice.
AB  - To date family caregiving studies have considered family caring in primarily
      practical terms such as 'how to do' and 'how to cope'. Research efforts have
      focused upon exploiting the productive elements of a certain conception of the
      essence of family caregiving. Thus despite a wealth of studies, the question of
      the nature of family caregiving is not well understood. This ontological
      hermeneutic study highlights the importance of understanding the human experience
      of family caring at home. The study involved in-depth audio-taped interviews with
      seven family carers who care for an older relative at home. Thematic analysis of
      the transcribed interviews uncovered a number of common themes which highlighted
      unique and shared meanings family carers ascribed to their everyday existence as
      carers. The findings will challenge practitioners to reconceptualize the nurse
      family carer relationship, to appreciate the many ways in which family members'
      involvement in care provides meaning and significance to their lives, and to
      understand family carers through a process of human relating which fosters
      families' meaningful involvement in caring at home.

PMID- 10210469
TI  - Family health in everyday life: a qualitative study on well-being in families
      with children.
AB  - This article describes the subjective health views of young Finnish families with
      children. The data were collected in unstructured focused interviews with 19
      families, most of whom were interviewed twice. Set within a phenomenological
      hermeneutic framework, the study applies a qualitative method in order to uncover
      the meanings attached by the families to different facets of their everyday life.
      Health is an integral part of the everyday life of families with children,
      comprising various dimensions of experienced well-being and unwell-being,
      security and different life-habits. Social networks are crucial to family health:
      they can either strengthen or undermine experienced health. Professionals working
      with families in the health care system need to have at least a basic knowledge
      of the different dimensions of family health: this helps to identify and
      understand the individual ways in which families work to promote their health and
      well-being. This knowledge of family health is also important for research
      purposes. Health care professionals also need to know more about how families
      cope with their everyday problems and about how client families can be supported.
      More research is needed on the concepts of family health and on how those
      concepts are applied to practice in different health care sectors and in
      education.